The Tim Ferriss Show - Ep 54: The Promises and Perils of the Microbiome - Dr. Jonathan Eisen and Jessica Richman

Episode Date: January 6, 2015

By popular demand, an entire episode dedicated to exploring the microbiome! Are you really 90% bacteria and 10% human? How can you manage or optimize your own microbiome? Should we do fecal-matter transplants from "untouched" indigenous tribes to reverse chronic illness? We tackle all this and much more. Jessica Richman is co-founder and CEO of uBiome, a startup backed by Y Combinator and Andreesen Horowitz, which uses citizen science to understand the human microbiome. Jessica attended Stanford University, where she earned degrees in economics and interdisciplinary engineering. She then got a fellowship to Oxford University for her PhD in computational social science. Her work has been featured in Wired, Popular Science, MIT Technology Review, NYT, and dozens of other media outlets. Jonathan Eisen is a Full Professor at the University of California, Davis with appointments in the School of Medicine and the College of Biological Sciences. Dr. Eisen’s research focuses on the evolution, ecology and function of communities of microorganisms. His study systems have included boiling acid pools, surface ocean waters, buildings, agents of many diseases, and the microbial ecosystems (also known as microbiomes) that are found living in and on plants and animals. In addition to his research, Dr. Eisen is a vocal advocate for “open science” especially “open access” to scientific publications. He earned a Ph.D. in Biological Sciences from Stanford University and an A.B. in Biology from Harvard College. ***If you enjoy the podcast, would you please consider leaving a short review on Apple Podcasts/iTunes? It takes less than 60 seconds, and it really makes a difference in helping to convince hard-to-get guests. I also love reading the reviews!For show notes and past guests, please visit tim.blog/podcast.Sign up for Tim’s email newsletter (“5-Bullet Friday”) at tim.blog/friday.For transcripts of episodes, go to tim.blog/transcripts.Interested in sponsoring the podcast? Visit tim.blog/sponsor and fill out the form.Discover Tim’s books: tim.blog/books.Follow Tim:Twitter: twitter.com/tferriss Instagram: instagram.com/timferrissFacebook: facebook.com/timferriss YouTube: youtube.com/timferrissPast guests on The Tim Ferriss Show include Jerry Seinfeld, Hugh Jackman, Dr. Jane Goodall, LeBron James, Kevin Hart, Doris Kearns Goodwin, Jamie Foxx, Matthew McConaughey, Esther Perel, Elizabeth Gilbert, Terry Crews, Sia, Yuval Noah Harari, Malcolm Gladwell, Madeleine Albright, Cheryl Strayed, Jim Collins, Mary Karr, Maria Popova, Sam Harris, Michael Phelps, Bob Iger, Edward Norton, Arnold Schwarzenegger, Neil Strauss, Ken Burns, Maria Sharapova, Marc Andreessen, Neil Gaiman, Neil de Grasse Tyson, Jocko Willink, Daniel Ek, Kelly Slater, Dr. Peter Attia, Seth Godin, Howard Marks, Dr. Brené Brown, Eric Schmidt, Michael Lewis, Joe Gebbia, Michael Pollan, Dr. Jordan Peterson, Vince Vaughn, Brian Koppelman, Ramit Sethi, Dax Shepard, Tony Robbins, Jim Dethmer, Dan Harris, Ray Dalio, Naval Ravikant, Vitalik Buterin, Elizabeth Lesser, Amanda Palmer, Katie Haun, Sir Richard Branson, Chuck Palahniuk, Arianna Huffington, Reid Hoffman, Bill Burr, Whitney Cummings, Rick Rubin, Dr. Vivek Murthy, Darren Aronofsky, and many more.See Privacy Policy at https://art19.com/privacy and California Privacy Notice at https://art19.com/privacy#do-not-sell-my-info.

Hit record. We're going to take just a couple seconds of silence and then we'll jump into it. Optimal minimum. At this altitude, I can run flat out for a half mile before my hands start shaking. Can I ask you a personal question? Now would have seemed an appropriate time. What if I did the opposite? I'm a cybernetic organism, living tissue over a metal endoskeleton. Meet Tim Harris Show. This episode is brought to you by AG1, the daily foundational nutritional supplement that supports whole body health. I do get asked a lot what I would take if I could only take one supplement. And the true answer is invariably AG1.

It simply covers a ton of bases. I usually drink it in the mornings and frequently take their travel packs with me on the road. So what is AG1. It simply covers a ton of bases. I usually drink it in the mornings and frequently take their travel packs with me on the road. So what is AG1? AG1 is a science-driven formulation of vitamins, probiotics, and whole food sourced nutrients. In a single scoop, AG1 gives you support for the brain, gut, and immune system. So take ownership of your health and try AG1 today. You will get a free one-year supply of vitamin D and five free AG1 travel packs with your first subscription purchase. So learn more, check it out. Go to drinkag1.com slash Tim. That's drinkag1, the number one, drinkag1.com slash Tim.

Last time, drinkag1.com slash Tim. Check it out. This episode is brought to you by Five Bullet Friday, my very own email newsletter. It's become one of the most popular email newsletters in the world with millions of subscribers. And it's super, super simple. It does not clog up your inbox. Every Friday, I send out five bullet points, super short, of the coolest things I've found that week, which sometimes includes apps, books, documentaries, supplements, gadgets, new self-experiments, hacks, tricks, and all sorts of weird stuff that I dig up from around the world. You guys, podcast listeners and book readers, have asked me for something short and action-packed for a very long time, because after all, the

podcast, the books, they can be quite long. And that's why I created Five Bullet Friday. It's become one of my favorite things I do every week. It's free. It's always going to be free. And you can learn more at Tim.blog forward slash Friday. That's Tim.blog forward slash Friday. I get asked a lot how I meet guests for the podcast, some of the most amazing people I've ever interacted with. And little known fact, I've met probably 25% of them because they first subscribed to Five Bullet Friday. So you'll be in good company. It's a lot of fun. Five Bullet Friday is only available if you subscribe via email. I do not publish the content on the blog or anywhere else. Also, if I'm doing small in-person meetups, offering early access to startups, beta testing, special deals, or anything else that's very limited, I share it first with Five Bullet Friday subscribers. So check it out, tim.blog forward slash Friday. If you listen to this podcast, it's very likely

that you'd dig it a lot and you can, of course, easily subscribe any time. So easy peasy. Again, that's tim.blog forward slash Friday. And thanks for checking it out. If the spirit moves you. As always, you can subscribe to this podcast on iTunes, and you can find all of the links and resources from this episode, as well as every other episode by going to fourhourworkweek.com forward slash podcast, spell it all out. Or you can go to fourhourworkweek.com and just click on podcast. Feedback, if you have feedback, I would love your thoughts, anything at all, who you'd like to see on this show. Ping me on Twitter at tferris, that's twitter.com forward slash t-f-e-r-r-i-s-s, or on Facebook at facebook.com forward slash timferris with two r's and two s's.

Hello, my clever little monkeys. This is Tim Ferriss, and welcome to The Tim Ferriss Show, where I dissect world-class performers, interview them, not literally cut them apart and dissect them, to try to extract the tools and tips and to find the resources that you can apply in your daily lives, whether those people be billionaire investors, chess prodigies, famous CEOs, celebrity types, or anybody in between. It's really a wide spectrum of expertise and you find commonalities. And in this episode, we will be talking to two scientists slash entrepreneurs, specifically about the microbiome. And many of you, literally hundreds of you have asked me to elaborate on the microbiome and what that

means and how I try to manage or improve my own microbiome. And we have two people on this particular episode. We have Jessica Richman, who's co-founder and CEO of uBiome, U-B-I-O-M-E.com, startup backed by Y Combinator and Andreessen Horowitz, which uses citizen science to understand the human microbiome. In full disclosure, I am also involved with this company. I helped them long, long ago and then ended up only recently backing the company. So we will talk a lot about that. And then you have Jonathan Eisen, who is a full professor at the University of California, Davis with appointments in the School of Medicine and the College of Biological Sciences. Dr. Eisen's research focused on the

evolution, ecology, and function of community of microorganisms. Both of these people are fascinating, very different personality types, And the conversation was a blast. So without further ado, please meet Jessica and Jonathan. Jessica and Jonathan, thank you so much for taking the time to be on the show. Thank you. Glad to be here. It's a really an honor to be here. And this is a distributed powwow.

I'm very excited about this. This is my first time doing this. Jessica, you are here in San Francisco? Yes. Yeah, in San Francisco. Right down the street. And Jonathan, you are in Vegas. I am in Vegas. That's right. In Vegas to settle some old debts, to settle some old scores. No. What are you doing? I'm doing a show. No, I'm going out to do field work in Death Valley tomorrow. All right. So this leads us to the very exciting topic and many topics I'm sure that we'll delve into.

I will start with a very boring question. It is perhaps the most American of all questions. But the what do you do question. But very specifically, I'll start with Jessica. If somebody asks you these days, I guess your answer might be somewhat straightforward, but what do you do? How do you answer that at a cocktail party if they still have such things? I mean, I don't know if I've ever actually been to a cocktail party, but when I go to conferences, people ask me that question. And I have to back up a bit and start talking about bacteria. And then either people get this really horrified look on their face or they get this very excited look on their face. Most people are not neutral about bacteria.

So I say, oh, well, I run a company where we sequence the microbiome. Those are the trillions of bacteria that live on and in our bodies. And then I sort of pause and wait for the look of horror or excitement to cross over their face to see how much more I should tell them about that. And that's a matter of time before we get into the subject of poop. Like I was gonna I was just, you know, I knew you were gonna bring it up first. This is a very Yeah, there's like a mean time to poop for conversation. So how much do you know about poop swaps? That's the the opener. I find that's a pretty good pickup line also. Yeah, yeah. You know, it works for me. So Jonathan, what about yourself? When someone asks you what you do, what is your answer? I'm a professor and I study and teach about and communicate about microorganisms.

And I want to define a couple of terms, partially because, in all honesty, and this is embarrassing, but I've never really defined these terms very well for myself. Microbiology. So you're currently a full professor at UC Davis, is that right? At the UC Davis Genome Center. What is medical microbiology and what is microbiology? What's a good way to think about that? Well, microbiology is the study of organisms that we can't see without the aid of like a microscope, some device. They're organisms that are invisible to the naked eye. And then, you know, within that scope of microbiology, there's lots of sub-disciplines that people have defined. I kind of hate all of those sub-disciplines, but

it's, you know, some people, you know, environmental microbiology is the study of microorganisms out in the environment, and medical microbiology is the study of microorganisms associated with human health, and there's veterinary microbiology and plant microbiology and blah, blah, blah, blah, blah. Now, do you dislike those classifications? Because it's kind of like saying breast cancer versus pancreatic cancer versus such and such cancer. And you're like, we should really be defining this by the type of microorganism, not the location, so to speak.

Or is it something else that bothers you about it? I mean, in general, I hate rules and I hate stovepiping. So I just think it's not that useful to isolate humans from other animals and to say that environmental microbiology is somehow different than the microbiology inside people. It's just arbitrary boundaries that have no value. Okay, I like this. This is a good start. And we'll certainly talk about it. You have a very interesting blog. What is phylogenomics? Or phylogenomics? I can never figure out. Yeah, phylogenomics. Genomics. There we go. It's both a good and a bad thing. I invented the word when I was a graduate student to basically refer to evolution, phylo is a sort of abbreviation for evolution, and genomics, the evolution of genomes,

basically. And I regret this because I also write in my blog a lot about the proliferation of bad new genomics words. But nevertheless, I invented the word and then I just named everything, all my blogs, all my lab sites, all my login accounts to various sites. They all have something to do with phylogenomics and I'm kind of stuck with it. Well, you own it. That's good. Yeah, that is true. I I'm kind of stuck with it. Well, you own it. That's good. I mean, you'll... Yeah, that is true. I own it and don't like it. And the evolution...

So the microbiome, and I'm wading very deep into the pool of ignorance on my part when I get into the microbiome, but it became of great personal interest to me because I contracted Lyme disease, went on very long-term, from my perspective, long-term use of broad-spectrum antibiotics like doxycycline, and started to suffer from all sorts of health conditions that, from my assessment, were not caused by Lyme disease, but were caused by the long-term use of antibiotics. So I started to have skin disruptions and all sorts of issues that are associated with chronic illness. But I had not drawn the connection between some of these supposed chronic illnesses and microbiome. A friend of mine who is sort of an amateur microbiologist, for lack of a better

term, suggested that I start taking L-plantarum and a number of other types of probiotics. And the symptoms, I had this breakout on my feet, pretty much overnight down by 50% in terms of symptoms and then proceeded from there really quickly. And so I'd love to know, what are the biggest misconceptions? And this is open, maybe Jonathan, if you want to take a stab at this, what are the biggest misconceptions about the microbiome? Because it's become a hot topic. Obviously, the fecal matter transplants are very exciting for the media. And that would lead me to assume that there's a lot of voodoo and nonsense also being spread therefore. But what are the

biggest misconceptions about the micromyome? Well, I mean, I think that the thing that I, the reason I am interested in this from a research and a communication point of view is because there's enormous promise from a medical and agricultural and environmental and evolutionary point of view. I mean, every plant and animal is covered in a cloud of microbes, and they clearly influence the biology of these things that they're living on. And so there's enormous promise. And there have been a few papers in the last five to 10 years that have shown really big impacts of this cloud of microbes on the health of various organisms but the the part that is also interesting and sort of challenging is for whatever reason a lot of people have

oversold or over interpreted what we know about the microbiome and aren't doing a really good job of distinguishing what we think might be going on from what we know is going on so i give out an overselling the microbiome award on my blog and it's like it's literally like you know the easiest low-hanging fruit blog material that exists in my life. There's just so much out there where people make sort of fundamental miscalculations as to how to interpret some scientific study or some personal dietary change or other issues. Well, I mean, I think I'd like to add a couple of things to that. I think the first thing is that you noticed anecdotally this change, Tim, right? Like you take all these antibiotics, you develop this problem, you take probiotics, and it goes away.

And that's not data. That's just an anecdote. But I think— Yeah, and just in fairness, I recognize that it could be correlation, not causation. It could be regression to the mean. I understand all that. But still, I mean, I don't call it an anecdote to minimize it. But just to say that I think one of the interesting things that we're doing at Ubiome and I think is a general trend that is interesting is this crowdsourcing of science to enable things like what you experience to be validated in new ways. Because I don't think it was my feeling, but it probably was not just regression.

I mean, if it happened immediately afterwards, then you can sort of see the effects in your own experience. But why did that happen? And does it happen for everyone? And how often can that be replicated? And all these kinds of things are important questions to be answered. And your anecdote is like the beginning of a hypothesis about how probiotics can affect the human body, not just something to be dismissed, I think. No, absolutely. I mean, I'd love to hear you elaborate a little bit on how you would define or think of citizen science, because I think we're leading into that pretty quickly.

Yeah, yeah. So citizen science is a term that was coined by the Cornell Ornithology Lab in the, I think, in the 70s. It's basically the idea that citizens, people that are not PhD scientists working in a research lab, can create interesting science by collaborating with scientists. So in the case of ornithology, it's really interesting. You know, there aren't enough bird watchers in the world, There aren't enough ornithologists in the world to watch all the birds. So they use amateur bird watchers to contribute data very frequently. And that's sort of grown in this idea that other types of scientists can include the public in their research, whether it's data collection or even going further, it's generating hypotheses, funding science, like we did at uBiome, open sourcing publication of blogs about their own experience, their own experiments.

And all these things are sort of citizen scientists, crowd scientists, people who are not employed in the job of science, contributing to science and adding a new perspective that isn't there in mainstream science. Got it. And I want to come back to you. Jonathan, I'm going to ask Jessica a few more questions, and then I want to come back to you and ask you. So you have so much experience with research. I'd love to ask you about sort of what is wrong with the current ways in which research is done or has to be done

and how you in a dream world would fix that because I think it's an interesting topic. But Jessica, I'd love to ask you just to give people sort of a taste and again, understanding that the plural of anecdote is not data, although I do have some issues with the overuse of that expression. I do too. I'd love for you to comment because we've talked about some of these things before, obviously, and I'm involved with, you know, I'm a backer of Ubiome and believe in the mission. And I was a supporter long before I was ever involved in a formal capacity. But could you talk about gut mood and behavior, maybe highlighting some of the things you found most interesting in the last few years? Yeah, so there's a lot of so.

So let me just back up for a second. So the obvious things that you think of when you think of the gut microbiome are, you know, health conditions that involve the gut. So you think about, you know, traveler's diarrhea, and you think about enteric dysfunction, and you think about irritable bowel or Crohn's disease, or all the sort of obvious things that involve your gut. But what you don't often think about are other health conditions that are much more systemic that relate to the microbiome. So there's been some interesting research about, mostly in mice, about how you can change a mouse mood by changing the mouse microbiome. And I know this sounds a little nuts, but there are measures for whether a mouse is anxious or depressed

or has autism, actually. It was an interesting study I was just reading earlier today. And basically, by taking germ-free mice, these are mice without any microbiome, and then by adding either an anxious microbiome from an anxious mouse or from a not anxious mouse, you can change the mood of a mouse. And this has been done in a number of different ways with other sort of mood disorders in mice. And there has been done in a number of different ways with other sort of mood disorders in mice. And there has been human research specifically on this. I mean, they notice different microbiomes in humans that have different mood conditions, but there's no causal research there. That's a really interesting area. And I think it's interesting mostly because it points to how complex the microbiome is and how complex its effects are. So it's not just, you know,

oh, the obvious, you know, you have diarrhea and that's because you have a microbiome problem. It's much more dispersed throughout the body and the effects the microbiome has can be much more subtle. Well, this comes back to something that Jonathan said about distinguishing between what we truly know and what we think we know. And there's often a very large discrepancy between the two. I mean, for a long time, it's thought that fat cells are basically these inert storage devices without much function beyond that. But a lot of endocrinologists have begun thinking of, uh, adipose tissue almost as, you know, what is basically hormone, uh,cing endocrine glands in a way.

And it's very active. I mean, there's brown fat and different types of adipose tissue as well. And I think that one of the things I've heard from some scientists I've chatted with about the microbiome is that the gut can be thought of as the second brain. But where I've lost track of the argument is how the gut, if it does in fact produce neurotransmitters like serotonin, or is it just that the composition of the microbiome in the gut then affects brain function in such a way that affects neurotransmitter production? Do you have any thoughts on that? I mean, it's all of those, right? Yeah.

Yeah, so there are a few hypothesized mechanisms. And Jonathan, maybe you can expand this more than I can. But to start off with, there's this idea that inflammation, that microbes cause inflammation in the gut, and then your brain misunderstands, feels that you're kind of out of sorts and inflamed, and then is anxious about that. And then you sort of assign that to your work situation or your romantic situation where really you're just kind of irritated because your gut is irritated.

So that's one hypothesis. Another one is that the microbes are actually making chemicals that induce behavior in you. So they're making you crave sugar because they want sugar, not because you need sugar. So maybe even making you crave things that you can't digest, but that they can. So it's a matter of survival for the gut microbes. The only way they're going to get fed need sugar so maybe even making you crave things that you can't digest but that they can this is a matter of survival for the gut microbes to you know they the only way they're going to get fed is if you eat what they want you to eat right so that's sort of another idea they're pulling a feed me seymour sort of yeah exactly so so i wonder if if we can take a step back for a second so um i've been and many other people have been working on how hosts, you know, animals and plants depend upon single bacteria, single mutualistic, you know, lots of insects need bacteria that live in their gut to make amino acids and vitamins they don't get in their diet.

And lots of plants get nitrogen via bacteria that live inside their roots. And, you know, organisms that digest cellul providing some critical function that the host biology in all sorts of bizarre, interesting, and damaging ways. And so in that context, it's almost obvious that the microbes that live in our gut and in our mouth and on our skin and in our other orifices and places have the potential to do all sorts of things to our biology. And again, if you, the way I think about it, I'm actually an evolutionary biologist. The way I think about it is, you know, animals have been evolving in this microbial world for hundreds of millions of years. Our evolutionary processes are in essence based upon expectations. And the expectation for our

gut and our immune system and our behavior and everything is that we're going to encounter microbes because we always do. And so our systems are tuned towards, you know, predicting and responding and dealing with microbes. So I mean, in that context, it's sort of, it's almost obvious that microbes that are in and on us are fundamental parts of our lives. And to give, I'd love to do a quick fact check. I've heard that, I've heard people say that humans are really 10% human, meaning by volume or number of cells, 90% of us is comprised of bacteria. Is that, I mean, I think. Yeah, there was a really good fact checking that someone finally did in, I think in the

Boston Globe, where it turns out that number, which had been quoted for 20 years or so, is almost completely made up. But better estimates are probably something on the order of 50% micro. But I don't think that the total number of cells is that interesting. What I think is more interesting is that in our mouth, there are probably, in each individual person, there are probably something on the order of 500 species or 1,000 different species of microbes. And in our gut, there are 1,000 in each different compartment, and they're not always the same. So the things in the stomach are different than the things in the ileum are different than the things in the colon. And then on our skin and in different parts of our skin, I mean, we are an ecosystem with an

incredible diversity of types of organisms and functions. And yeah, each person, it's going to vary how many they have, how many cells there are. It's going to vary over time, but we should view ourselves as a walking ecosystem, not as an individual human. And if people wanted to learn more about the microbiome, well, actually, let me take a step back. I promised I would ask a question, so I will ask that. And that is, for researching the microbiome or anything else, how is it currently done and how would you change it? What are the issues with accelerating good research in this field or any other for that matter? Well, I mean, I think the reason everybody is excited now, the reason that Jessica was able to start her company and the reason that there's a lot of stuff going

on is that the technology for studying microbial communities has gotten much better and much cheaper in the last few years and primarily the way people do this is using analysis of the dna from a sample and the reason we do that is most of the microbes in any particular environment can't be grown in the lab and we can't identify them very well in a microscope but and we can crack them open and we can look inside of them and we can look in particular at their genetic material, their DNA. And that DNA contains a lot of information about the microbes that are there that helps you identify what kinds there are and it helps you predict what their functional potential is. And so in that context, it's like, I'm like a kid in a

candy shop. I mean, it is the golden age of microbial ecology right now. So I wouldn't say there's a ton per se I want to change. I mean, what I really want to do more than anything else is engage the broader community in thinking about microbes just like Jessica is trying to do. We're limited by the number of samples we can get. And what we want is 100 million samples, to be honest. And I can't do that myself. I need a million people to help me collect samples. That's what I want to get people to think about. I agree with that. I mean, I would say I have a lot of thoughts on this because it's something we think about a lot and how to make research accessible to the public, how to make it larger, more scalable, more, you know, more actionable in people's lives. And I

think larger studies is a huge one. I think that, you know, you can have a very respectable study in a major peer-reviewed scientific journal, Nature Science Cell, something like that, and you can have 100 people in it. And I just think that that's going to seem ridiculous 10 years from now, 15 years from now, when it's just obvious that you can source study participants more easily and that you can involve the public in your study and just have things move much more quickly. So I'd love to see that happen. I'd love to see studies be more scalable and flexible so that, you know, you can start off with a certain study design, you know, asking a certain question. And then because you have, you know, your 10,000 participants or your 100,000 participants, you can sort of take a subset, say that's the interesting part, and then go forth with that group. So you can sort of take a subset say that's the interesting part and then go forth with that group so you can sort of make the whole apparatus of creating scientific studies better larger and more scalable yeah and i was just gonna say i mean i think that the one thing that maybe i would would say we we need to do in the future that we're not doing as much of now is that a lot of the work that we're doing,

it's incredibly exciting and really interesting where we can use DNA as a fingerprint of what's going on in the community. But this is building, in essence, some type of general profile of the world around us. And we can compare and contrast health and disease states. We can compare people over time. We can compare people before and after, like you, antibiotic treatment. We can do lots to get a general idea as to what's going on. But of course, that's just the first step. I mean, there's lots more really interesting biological studies that can be done once you have this sort of framework that comes from characterizing the DNA of the community. So we can start to look at the functions actually encoded in these genes. We can do experiments to test those functions. We can look at where

individual cells are located in particular environments. So a fecal sample doesn't tell us anywhere near as much as a full microscopy staining of the entire gut. And things are floating around in the liquid. Some are on the layers of cells. Some are inside cells. I mean, this is the first step in characterizing this system. So I'm sorry, I was just going to ask So, yeah, I'm sorry. I was just going to ask quickly. Well, just a couple of observations for people who are listening, who are from a lay audience like I am. I'm not a trained scientist.

I mean, I read just enough to be dangerous and have spent some time at UCSF with a couple of the neuroscience labs. But I think that the I want to come back just briefly to the, the plural of anecdote isn't data, uh, because this is, this is a term that is used a lot by people who don't really understand the design of scientific studies. And, uh, I think it's worth just pointing out a few things and I please jump in and correct me or, or, uh, edit anything that I say. But if you look at, for instance, the development of smallpox vaccine, which was introduced by Edward Jenner in 1798. So

he observed, and one could say this is anecdotal, that milkmaids who had previously caught cowpox did not later catch smallpox. And the way he demonstrated this could be causal is he, as I understand it, basically took cow pus and injected into his family. And needless to say, pretty ballsy. But the point being that the observation helped him form the hypothesis, and that could be derided by this, the plural of anecdote is not data. And when there's a study, I mean, you brought up 100 subjects, right? So oftentimes people from a lay audience will say, oh, there are only 10 subjects, like that's a bullshit study. It's like, well, there are a couple things you have to look at, right? You can look at the number of the N, you can look at the number of subjects, but you have to also look at the amplitude of the change

from the intervention right if you're doing a control and experimental group so if you have 10 people but they they all double their working memory well okay there might be something interesting there in terms of the the p value right and the the likelihood that that's attributable to chance is rather low i'd say tim like Tim, like, I think that's true. I would say the plural of anecdote is hypothesis more than it is data, right? I mean, that's kind of the example that you're giving. Well, right. So, I mean, I think that, I mean, my personal view on this is that many scientists, many

of the supposed cognizanti, just are assholes. I mean, let's just be clear. I mean, you know, like, they say things like that because they want to put themselves up on a pedestal. And I think that if you go back to your question about the future of experiments and science in general, I mean, I think what we need in the future is for much more of these observations all the way through to clinical trials to be published and to synthesize the collection of knowledge from across the planet more than need suppression of work that people do simply because one person thinks it doesn't have enough statistical sample size or something like that. I mean, that is the ultimate. And in fact, I spend half of my time working on scholarly communication and open science, not on microbiology. And I think that this is the biggest issue that we have right now is trying to broaden scientific research and not to suppress it. And I just,

it drives me crazy. It makes me just go insane when I hear anyone say anything like that quote. And I hear this all the time in graduate student committee meetings where one person will say, well, that's not hypothesis-driven research. That's discovery science. And God, just get out of science for God's sake. Well, this brings up a follow-up question I'd love to ask you, which is if you had, let's just say, $5 million to use as you see fit in off to Monaco and buy Lamborghinis, you can use this for almost anything you want. How would you spend that? I would invest it in lots of small projects. What types of small projects? You know, I think that what I see is that creativity by researchers, by citizens, by graduate students, by undergrads, by high school students, that the creativity that people have about science, about microbiology, once they learn about microbiology, is enormous. And what we need to sort of support is ways that those people can leverage their

creativity to do a research project. And what I would not do with the money is say, give one person the $5 million to do a big project. I don't think that that's, we have a lot of those projects anyway. And what I really think we need is to harness sort of the anecdotes, the observations that people have made. They may not all turn out to be useful interpretations, but there's a lot of stuff out there that needs to be studied and we need more people doing it. Yeah, I think it's interesting. If I had $5 million that someone handed me to do this kind of research, I think you're right. I would break it down into small chunks. I think that makes a lot of sense.

You sort of let a thousand flowers bloom, sort of see what comes out. But I think in terms of the microbiome, what's most interesting is to accelerate the process of taking these sort of correlational studies that we have now, which say, oh, isn't this interesting? People with X health condition, whether that's anything from Crohn's disease to autism, people with that health condition are different than people that don't have that health condition. I think that's sort of the state of a lot of the research. And I would use that money to do a number of studies that would move the research to the next phase, which is great. Okay, where's our diagnostic and where's our therapeutic based on that? Because I think the real power of the microbiome and what's sort of magical about it is that

these microorganisms are both sort of biosensors that can tell us what's going on in the microbiome. At the same time, they're also drugs, right? Like they are organisms that when you put them in the ecosystem of our body change the outcome from a clinical perspective. And I think that moving things from this sort of associational stage to a specific, I don't know, you could call it a product stage, but to a specific improvement in outcomes, I think that's going to happen anyways because a lot of people do have $5 million and they're spending it on that, which I think is great. But I would also take my $5 million and knowing what I know now from working on eBiome, I would put that to good use in those areas.

Well, I think the micro experiments are really undervalued because for whatever reason, it seems like a lot of the scientific community undervalue the things that cost very little money just because of advances in technology. And for instance, I mean, and this might seem like a silly example, but the late Seth Roberts, very smart guy. I mean, very good at crunching numbers and spotting methodological flaws. But he introduced me to this very simple. And there was a fair amount. He did a fair amount of literature review to try to figure it out.

But just the combination of vinegar plus honey in hot water before going to bed. And I was able in the span of about 48 hours to have several thousand readers test this. So people who had insomnia to test it and compare it, obviously subjectively, sort of qualitatively with other things they had tried, like Lunesta or whatever. And it was astonishing how positively people responded, but I struggle with how to sort of gather that and codify it and present it in a way that can be graphed intelligently, right? That's absolutely it.

Yeah, I mean, right, because that's a valuable study. If you just put a hypothesis in the data with large numbers, right? With the law of large numbers. If you have enough people, you can smooth out a lot of the rough edges. Let me dig into a slightly different question. And Jessica, I'll toss this to you first. A lot of people think about probiotics, right? And there's obviously a huge industry around probiotics. I think some of it, even from my untrained standpoint, look pretty nonsensical or they're pushing the claims really far.

Or they're using, for those people out there who don't know the term puffery, I don't know if you guys have ever heard this expression. So there's a legal definition. Puffery is when you make claims that are nonsensical, they're non-falsifiable. So if you buy a shampoo that says, you know, beta hydroxylizing hair volumizing formula, that's puffery because it's all fucking bullshit. And, and, and that kind of stuff is used all the time in supplements, right? It's like, you know, increase your vitality and blah, blah, blah. Okay. Vitality, puffery, bullshit. But the, what I wanted to chat about, because

I had this planted in my head by a friend who's, he's, he's an amateur scientist, but in the same way that I'm not going to say Darwin, but I mean, people who ended up coming up with pretty fascinating things were amateurs. And he talked about the importance of more so than probiotics, basically treating your, for instance, gut microbiome like a rainforest where you need to create an environment in which plants can grow. You can't just stick plants into the sand and hope that they'll take root. And so he has focused quite a lot on foods that have, whether it's say beans, lentils, things with fiber or prebiotics like baobab root and so on to help the body create an environment in which beneficial bacteria can thrive, as opposed to

swallowing a lot of pills with said bacteria within them. And again, all of this might be BS. I don't know. But how do you guys think about this? And Jessica, I'll let you go first. Yeah, let me start with that one. This is a great topic. I'm really glad you brought this up because I have a lot of thoughts about this. The first thought is to some degree, people have to use that language of puffery for legal reasons. I mean, they can't say, you know, this product is going to make you healthy in these specific ways. They have to say, increase vitality, which is total nonsense. Well, they can, but it's just expensive to get FDA clearance. Yeah, that's fair enough. It is expensive.

But I think people also use that puffery because, I hate to say it, but the current state of the probiotics industry is that if you have a study that shows that your probiotic exists in the bottle and is taken by the people that take it and shows up somewhere in their stool after they've taken it, that is a gold standard amazing study. Wait, wait. That's like if it's excreted, meaning like the Olympic athletes having the most expensive urine in the world. Right, exactly. It's really, I mean, I think this is, I mean, no, no fault to the probiotics industry here. This, this kind of testing to better understand the microbiome is only possible in the last few years. So this is why they haven't done this yet, but this is a over $30 billion a year industry. It's a huge industry. And basically the science supporting it just hasn't been there. So I was at this conference that was

a nutrition business journal conference, and there were all these executives there from the nutritional supplements industry. And they're just starting to start to figure out how are we going to, in an age where everyone can test things about themselves, the age of the quantified cell, and in an age where DNA testing of bacteria is pretty much ubiquitous, and we charge $89 each, so that's like really cheap. You can do a lot. Everyone can basically test themselves. How do they make sure that their products are actually doing something and are actually valuable? And so I think there's going to be this, I think the probiotics that you see on the shelves today in Whole Foods are going to be totally different 10 years from now because the public will just demand better. They'll say, well, wait, I took this and what's it doing for me?

And because of science, it'll be possible to do better. So I think there'll be way, the probiotics industry is poised for this tremendous leap into better products that actually do a lot more for you. And it can be tested sort of apples to apples with prebiotics, like you said. Like, are prebiotics better? Well, it probably depends on who you are personally. It depends on your health conditions. It depends on sort of are the probiotics that are written on the outside of the bottle actually in that bottle? That also is a big factor.

Well, yeah, there's that too. I mean, it sounds silly, but that is actually a huge factor, right? Like if they're not, there's currently no sort of testing for what's live. So I think there's going to be a big change in that industry as these new technologies sort of work their way through and people develop better products going forward. Yeah. Did you buy an expensive bottle of Dead Sea Monkeys? Yeah.

Yeah. I'm sorry, Jonathan, go ahead. complex like an ecosystem is, you know, there are ways that we should be thinking about this ecosystem that probably, you know, the simple model of probiotics just didn't take this into account. I mean, really, we need to think about the dynamics of competition going on in the ecosystem of the different members competing with each other for food and for space. They're going to grow and reproduce at different rates within the system. But just like any other ecosystem, there's going to be influx, that is new organisms coming into the ecosystem. There's going to be efflux. And, you know, there's 200 years of ecological research on studying these things and you know probiotics are

um you know have the potential to impact the system because if you have you know a massive influx of some individual species into an ecosystem it can impact it either on the short term or the long term but it it's a very simple component of the total picture of the ecosystem. So just a good example of this is if you take a savanna or a chunk of savanna and you isolate it and you introduce into that savanna a thousand cattle, they're going to disappear pretty darn fast. But if you introduce a thousand zebras, organisms that, you know, roughly the same type of organism, but they're kind of adapted to living in that ecosystem, they're going to do differently. And if you introduce, you know,

50 species at a time that actually represents something akin to what is naturally there in the ecosystem, that's going to be really different than introducing a billion of one kind of organism. So I think the more we think like ecologists, the more we think about the dynamics of the ecosystem that is the gut or the mouth or the vagina or the skin or wherever there are lots of microbes, the more we're going to be able to make sense out of the puffery that is associated with the promotion of certain treatments, and the more we're going to move into a system where it is useful. No, definitely.

And the conversation brings to mind a past conversation I had with a really, really fascinating guy named Steve Rinella. He's a hunter. He's the one who introduced me. I have never been a hunter, but was introduced to it for researching my last book when I wanted to hunt and forage for all my food for a period of time. And he was talking about the sort of politicized response to reintroduction of say wolves and how when you try to oversimplify it, just like carpet bombing your system with 20,000 pills of fill in theank single type of probiotic or bacterium that you could introduce, say, wolves are dying at an alarming rate. They're nearly extinct in this one place. Let's

add a thousand wolves. Well, that doesn't really work very well because it throws the entire system out of whack. And then you have, then you have, you know, basically a mass genocide of, you know, their primary prey. And what he pointed out also, and I think this is kind of interesting is that the microbiome people associate, I think broadly with the gut, right? They think microbiome, they think I swallow pills, put them in my gut and they're reading about fecal transplants and whatnot, but there's, it's a lot. And, and as you mentioned, Jonathan, even in the, the GI tract, you have these vastly different populations in different areas. And what Steve pointed out, he said, you know, people are against hunting wolves, for instance, because they're thought of as very sparse.

But the fact of the matter is they're very, very, very overpopulated in very specific areas. And therefore, the averages are misleading. So you should actually hunt and cull in certain places. But I'm getting a little down the rabbit hole with this story. But I'd be very interested to hear, Jonathan, you comment on the, just from the evolutionary standpoint, how do people go about figuring out what to aim for when it comes to that ecology, right? Because in a natural environment, you could say, wow, everything's going to hell in a handbasket. Something is wrong. It's kind of perhaps more obvious to pinpoint problems, but should we be looking to tribes in Tanzania or

Papua New Guinea or the untouched parts of the Amazon, if anything, exists like that to try to where the children haven't had antibiotics? I mean, how do you determine the menagerie of bacteria and the balance to target or to aim for? Yeah, I mean, it's actually a very complicated question and a complicated sort of research topic. Certainly, understanding where our microbiomes used to be in the past is a very helpful component of answering your question. So if we can get access to, you know, mummies and bog people and Iceman and other ancient samples, microbial studies of those samples are being done. And they're very important for placing what we see now in an evolutionary context. And other people are going out and

looking at populations of human, just diverse sampling of the human population, but looking at populations that have been less exposed to certain types of food or certain types of drugs or certain types of environments. And that is also providing that sort of context. I mean, we, in my research, in my lab, we actually work on the methods by which you would compare to evolutionary relatives or to ancient samples to try and figure out what the microbial community used to be like. And the reason you want to know that is twofold. You want to know, you know, what the immune system and what the organs and what the blood and what the rest of the body sort of evolved to see. And you also want to know how it's changed with humans. Obviously, we want to know how it's changed in response to antibiotics and in response to changes in diet and in response to globalization and other issues.

Now, that still doesn't tell us what the goal should be, right? Because we live in a world now that's different than the world we lived in 20,000 years ago or 20 million years ago. But it gives us sort of that framework to help interpret when you then do a study, say, of comparing people in Japan who live in Japan now to people from Japan who moved to the United States. There have been a few microbiome studies like that. And it helps you figure out what the disturbance is and what that might mean for our biology. But I don't think it's, I don't think it's obvious how to say we should have a goal of making our microbiome like it used to be 20,000 years ago. I mean, we have different diets, we live different lifespans, we have different interactions with other communities, it's pretty hard. Yeah. No, it seems extremely hard.

Jessica, what are some common disruptors of the microbiome? So it's certainly difficult to decide what the ideal should be, but what are we aware of that can disrupt or cause problems with the microbiome. So I've read certain, I wouldn't call them studies at this point, but that things like Splenda, artificial sweeteners, can cause issues with the microbiome. What are other common disruptors of the microbiome? That's such a good question.

So I just sort of want to start off with that point about there is no ideal microbiome. I think that's important. There sort of aren't, you know, people often ask also about are there good bacteria or bad bacteria? And really, from an ecological perspective, you can't say, you know, a good bacteria in the wrong place is a bad bacteria or a good bacteria at the wrong time. So I think some of that exoticism about, you know, let's go back to our ancestors is not, you know, a way to find the right, you know, to learn how to cultivate your microbiome, I guess. But in terms of disruptors, so there's, I mean, obviously, let's start off with the number one elephant in the room disruptor, which are antibiotics, right? I mean, we see this in the results of people who have taken our test. When you take antibiotics, you know, a day later, your microbiome, their whole, you know,

genuses of the microbiome, they're just not there anymore. And presumably they come back, you know, as you test your microbiome, as your microbiome recovers from the shock of the antibiotics. But it's definitely, you know, very clear that taking antibiotics just kills whole swaths of the microbiome. The study you're referring to about the artificial sweeteners was showing that artificial sweeteners can affect the microbiome in the way that sugar can. So I don't know if it's so much of a disruptor, but I think the big thing is sort of changes to the microbiome in terms of diet. So there's some really interesting research about people, you know, what happens when people have celiac or people who are gluten intolerant eat gluten and how that affects their microbiome and how it just increases inflammation tremendously

even after they've stopped eating gluten, presumably through the mechanism of microbes that are still there for when they ate gluten and are still causing inflammation. There's some interesting research around dairy that shows some similar things. So it's kind of all the usual suspects in terms of what we think of as disturbing our gut is also shown to have impact, to mediate some of that impact through the microbiome. Can I add just, there's another component that I view of as a really big, quote, disturbance, and it's more of a disturbance relative to what our bodies evolved to sort of expect. And that's, you know, early in development, cesarean sections, for example right or feeding formula instead of breast milk or excessive cleanliness as a child there's a lot of epidemiological data and some microbiome data

that shows that um you know all of those things that you know in, change the colonization pathways for how a young human being will get colonized can lead to longer term problems. And I view that as a disturbance in the microbiome because, you know, vaginal birth can be viewed as a delivery mechanism for microbes and as a component of it. I mean, obviously, it's not the only thing, but breastfeeding is clearly intimately tied with development of the microbial community. And, you know, even playing in dirt and experiencing the microbial world in some normal setting, that's what we evolved in that type of environment and whenever we disturb that whenever we deliver by c-section or have antibiotics or don't breastfeed or are excessively clean or have all

of these things that are not the normal developmental path it's not that those are always bad but they change the way our system sees microbes and And some of the time, our system's response to that is inflammation, or problems with the immune system development, or, you know, other types of developmental abnormalities. And I think that... Oh, sorry, go ahead, Jonathan. I was just gonna say, I think that those should all be viewed as disturbances, too. Definitely. So there's some interesting research about autoimmune disorders. And the hypothesis is that autoimmune disorders develop because the body doesn't have,

I mean, sort of the hygiene hypothesis sort of on steroids is that even autoimmune disorders are not caused by current, you know, lack of microbes, could be caused by lack of microbes at a specific point in human development. So, you know, you take antibiotics in your first year, it triggers something in certain, certain individuals who have a genetic predisposition to develop Crohn's disease, for example. And that, that part isn't proven, but I think it's very interesting because you want to look at microbial development on a timeline, not just what happens to be present in your gut right now, but what was present when certain events occurred. No, that's a really fascinating way to look at it. And Jessica, you introduced me to a gastroenterologist that maybe we can name another time, but since

I'll be talking about our conversation, I won't name her right now. Very, very bright. And she asked me quite a few questions. And one of them was about my antibiotic use when I was a child as opposed to adult and how that could contribute or not to immune function now, even though perhaps I had, as I did, for instance, chronic sinus infections when I was a kid. So it's really fascinating looking at the chronology of your microbiome to sort of follow the gingerbread trail to your current state, not just looking at the snapshot of the current fingerprint of your microbiome is interesting. So what I'd love to do is I think, and maybe it's natural that I would think this, but I, I just, I think that it would make a ton of sense to take sort of a fecal bank when,

you know, at various times in a person's life so that when later we have the technology to create, you know, artificially that community of microbes, you can give it back to you. So that's a good idea. Wouldn't it be awesome, right? You take your gut right now, which when it's relatively good, if it is, or your gut throughout certain points in childhood, you bank that sample. And then when we know how to recreate microbial communities better than we do now, you just say, oh, I want the gut of myself at 25, or I want the gut before I had an onset of Crohn's disease.

Well, okay, great. We'll tell you exactly what was in it and we'll give it back to you. Oh, here's a question. Jonathan, is that technologically feasible? I mean, if you had access to the nitrogen and apparatus to freeze it, like a sperm sample or stem cells or whatever, could you bank fecal matter or would it just obliterate the... No, no. So first of all, people are doing exactly that. They are, for their children, freezing fecal samples with the hope that either they will be characterized in some way, like with DNA analysis in the future, or that you could recover the living

organisms from those samples. You can certainly recover living organisms from samples if they're frozen in the correct way. There's this stool bank fecal transplant organization that was started by people from MIT that is doing exactly that, trying to store fecal samples for fecal transplants for future. There's definitely the technology to do this at least at some level. I don't think we know how to identify which of the samples are the ideal sample and you know not everything survives that freezing um so you can't necessarily recover the entire microbial community but but there are there i know multiple researchers who

are doing exactly this collecting samples weekly monthly or something that affect storing them characterizing them in some detail, and then, you know, anticipating as part of a research study, restoring some from the past if something goes wrong. So we do. So this is something we offer to people, you know, if you sample your microbiome now, even, you know, even if there's nothing particularly interesting you find in your sample, although that's unlikely, it's possible, then you can, you'll still have it. So we'll know what was in it. And maybe I think, I think where the technology isn't there yet is in, like Jonathan said, in bringing the microbes back to life. You know, the Lazarus microbe doesn't exist yet, but

certainly the characterization is there. So certainly you can say, you know, here's what it was like. And when the technology gets to the point where you can actually then recreate that community or infuse that community in the proper way that you'll at least know what was going on at that time. Well, it seems like, you know, as Jonathan mentioned, I mean, as we are able to identify and classify more microbes, and of course, we're limited in terms of the big picture, the complete picture by what we're able to identify. And Jonathan, maybe you could talk to this, but it doesn't seem like from a sort of usage of recombinant DNA and replication of these bacterial strains, like you could figure out the percentages and have sort of the, you know, like synthetic poop made to order kind of thing to implant at

a later date in time. I don't know. That's pretty exciting. I know I interviewed a woman named PhD Rhonda Patrick on the podcast not too long ago, and we were talking about banking stem cells and how parents can keep the child teeth, the teeth that are lost by their children for stem cell banking. And it seems to make a lot of sense. I mean, I can imagine after this podcast, there's going to be some intelligent and proactive tech millionaire who decides to have a poop cellar right next to his wine cellar with just a gazillion samples. Because unlike freezing eggs, humans, at least most of them, seem to poop quite a lot. So there's no shortage of material. So I just want to say that's something we promote to people, that you can have that sample.

I mean, the cool thing that's interesting also about banking poop is that let's say the analysis methods of today are not the right analysis methods, right? Like we do 16S sequencing. You can also do full metagenomic sequencing, which is sort of finding everything that's in the sample. Let's say none of those work and we actually need some totally other method. If you at least have the sample, you can go back using the method of, you know, five years from now, which is way better, and use that to do whatever kind of analysis that you need. Yeah, no, definitely. I mean, I've been, since it's, you know, just us, just us on the phone here. And a million other people, literally.

Hi. I have been banking sperm on and off for the last five or six years. And one could argue, well, you're 36, 37. It's already too late, pal. Your sperm is definitely past its prime. And be that as it may, which I suspect it is, we do not know what technologies or techniques may become available in the future for sort of rejuvenating or modifying those samples also. Right. So there's no,

from my perspective, it's just like, well, look, if you're spending hundreds of dollars a year on car insurance that you never really use, cause you don't get in an accident, what's the harm in spending an equivalent amount on storing biological material

that could prove, even in a 10% chance, to be very, very helpful and could even save your life at some point or something like that? That's a really good example on an individual level and also on a scientific level. I was talking with someone in the U.K. about NHS banked samples and how, because it's the National Health Service, they bank all their hospital samples. So they banked their fecal samples and blood samples going back to World War II. Like how interesting is that, right? Like from a personal perspective, yes, of course you want to bank your own sample, but also think about being able to like license the use of those samples or just give that data to a researcher that's studying something really important that you, your family could benefit from or a future sufferer.

I mean, there's just sort of possibilities are endless there to be able to take that data and make it valuable once you have it. So let me ask sort of a curveball question. It's not too crazy. It's just unrelated to what we were just talking about. And the question is going to be, what do your close friends think you are world-class at? And Jonathan, I'd love to maybe have you take a stab at that, if you wouldn't mind. Social media. As far as I know, that's all they know about what I do. And branding, phylogenomics.

Yeah, exactly. Making up words that isn't on the list. And studying weird microbes. So within the world of studying weird microbes, what are you known for, would you say? I mean, in response to what would someone say, ah, Jonathan's the guy you need to call to talk about that? Yeah, I mean, I think it's using an evolutionary perspective in trying to study or design ways to study individual microbes or communities of microbes. So, you know, a lot of people, a lot of researchers do great work on characterizing a particular

microbe or a particular system, but they're focused on just that system with a lot of their work. And what I really am known for, I think, and what I specialize in is saying, yeah, that's really interesting. But on top of that, it can be really helpful to understand the history behind that organism. That can tell you what direction it's going, where it came from, and allow you to make predictions about where things are going in the future. So I think my whole career has been basically taking that one theme, adding an evolutionary perspective, and applying it in a lot of different areas, and just hopping between genomics, so that's phylogenomics, and microbial communities, and functions of microbes, and how organisms survive in extreme environments

and what lives in and on humans or on other organisms and always saying, oh yeah, but what about the history? Right. I really want to ask you a question, but before I do, because I suspect it might fit in this category, what are the questions that you get asked from an evolutionary standpoint or evolutionary biological standpoint that are most irritating to you? What is the most ancient microbe alive? When all microbes are all equally ancient right now, none of them are old. They all grow and replicate. That always drives us crazy. Another is why the classical intelligent design

questions, I guess I don't find those as irritating. I get a lot of them, but I don't find them that irritating because they're so common. And I think another really thing that, I mean, I would say completely drives me crazy, and I get this question a lot, is why study that in microbes? Microbes are so simple. That's a rather condescending way to put it. Yeah, I know.

It has so many layers of inappropriateness and condescension, I don't even know how to respond sometimes. You just sidekick them. I find that pretty appropriate. So the question I was going to ask you is, how did Adam and Eve ride to their wedding on a dinosaur? That's really what – no, that's not my question. I'm kidding.

The microbes made them do it. The microbes made them do it. That's driving behavior. Those dinosaurs had a lot of sugar. No, the question I wanted to ask you, which is off base, but I just get asked this so often and I would love to have a more informed answer to it is, uh, and if this is outside of your, of expertise, please feel free to dodge. Um, but what have, uh, how should one answer the question, uh, or let me rephrase it. What do you think of the paleo diet or vegetarianism? I'll just throw those two out there.

You know, the vegetarianism and, I mean, any, I hate all rules, first of all, in all sorts of different environments. So anytime someone says I'm going to apply some rule to my life or to science or to something else, I kind of get irritated by it. But, you know, the paleo diet, I think, is a great example of something that is really interesting from a conversational point of view to think about, you know, how people used to live and what they used to eat. But to apply it to, you know, our modern lifestyle as though it's going to somehow be magically perfect seems a stretch to me. Let's put it that way. Are you trying to tell me that cavemen did not eat coconut macaroons? No, I don't think so.

I'll be very disappointed. did a lot more than we appreciate as you know they just discovered those supposed etchings on a shelf from 500 000 years ago and we're always finding new interesting behavioral patterns in neanderthals and in cave people i think we under appreciate what what the ancient human lineages did but i certainly don't think imitating everything they did is the right way to go. Yeah, I don't have a particular dog in this fight. What about vegetarianism? I mean, I think from a health benefit point of view, I think it's not necessarily, it's also sort of, you know, it could be good for some people, not necessarily good for every person. I mean, I think that that's a separate issue from the political point of view. I mean, I think very clearly the current mode of production of meat on this planet has enormous

ecological and health problems associated with it. That doesn't mean like going out and raising your own cattle and hunting and other things wouldn't you know be relatively not as damaging to the planet but you know production cattle uh and you know chicken farms and other things are causing enormous problems with global climate change and with antibiotic resistance and with the origin and evolution of pathogens. I mean, they're just a nightmare, basically. So vegetarianism, if you're doing it, you know, from a political point of view, I can understand it. I'm not one, but I can understand it. Yeah, no, I think just to underscore something for folks, if you avoid antibiotics, but don't discriminate your sort of animal protein consumption, you probably are taking antibiotics. You are, not probably, you are. Yeah. And so it's what's important to realize,

I think, among many other things, it's kind of a haughty way to start a sentence, but I'll start it with that way anyway, is that people say you are what be as good for you as eating, uh, locally grass fed beef, for instance, uh, nor is it necessarily better for the environment. Uh, so I think taking it sort of looking at these, the secondary and tertiary steps is important or, uh, preceding steps. Uh, you mentioned, uh, a distaste for rules, and I want to talk about this for a second because how do you distinguish – and maybe you dislike both. This is a fine answer, but I find it very – for me to be maximally productive, I find applying constraints very helpful, using different types of constraints. So how do you personally distinguish between rules that stifle versus constraints that enable? Yeah, I mean, it's funny. I just had a two-hour conversation with someone about this yesterday.

I think that the difference is whether or not you're going to apply them blindly or whether or not you're going to apply them with an open mind and intelligence. And the way I view rules is they're applied blindly. And the way I view constraints like you identified is sort of like a slight difference in the probability that you would allow yourself to not follow them right right so one is the i told you so because i told you so school of thought versus um sort of strong uh like a hypothesis weekly held or guideline weekly held uh very interesting what and then so so just as an example i I'm a type 1 diabetic, been on insulin for 30-something years.

I tried many times to have rules about, you know, don't eat dessert or do this type of diet or take insulin at this time. And I found certainly in my life that I never can follow those rules anyway. And it just became completely stifling to worry about whether or not I was following those rules. Whereas, you know, if I say, have dessert when you want it, but don't have it too often and be careful about it, I view that as a constraint and it works much better. How did, no, if you don't mind me asking, how old are you currently? Gosh, that's a good question. Should I know this? I am 46.

So is there, do you have any hypothesis or maybe you know how you, did you have type one diabetes prior to being 16 or, and it was just undiagnosed or did it, was it, did it have a sudden onset? Uh, when I was almost 16, um, over a period of maybe four or five months, I slowly started to waste away to the point where I was, uh, at lost about 45 pounds, um, and was probably within a few hours of being dead when I finally went into the hospital. And the sad, funny, interesting part of all this is my dad worked at the NIH and was trained as an endocrinologist. And I had mentioned multiple times that, you know, something's wrong. I'm really tired. I'm thirsty a lot. And, you know, he was blind to the, he was a researcher, so he didn't practice much anymore.

But, you know, I knew something was going on, but I didn't quite know exactly what. And it's like the frog in the frying pan thing. For me, it happened over such a long period of time that I just, by the end, it was ridiculous. I mean, I was going, I was peeing every five minutes and drinking, you know, 40 liters of liquid a day to try and keep up. And yeah, and completely ridiculous, right? And putting, I mean, it ended when I was on a backpacking trip, my first one in my life,

and I was putting my face into puddles of mud to drink the water. And, you know And at that point, something finally clicked in my brain like, this is wrong, and insisted on getting checked later that day when I was on the edge of diabetic ketoacidosis. Wow. Yeah. That's terrifying.

It was pretty messed up. What inspired you to become a scientist, if that's how you would characterize yourself? I mean, obviously, you have a tremendous amount of scientific and research background, but what inspired you to take that path? I'm from a family of dorks. So in particular, my grandfather was a physicist, did X-ray crystallography and other types of sort of theoretical physics. And he just talked about science all the time when I was a birder. I participated in some of those citizen science bird activities when I was a kid, doing Christmas bird counts and Thanksgiving bird counts. And I got really interested in natural history because of that. And I actually went to college and I was an East Asian studies major for a while, but I realized that I was too interested in biology. I actually took a course with Stephen Jay Gould on evolution and realized, oh, I can't do East Asian studies. I just love science.

I love biology and I love natural history. And that's what I view I'm still doing, natural history of microbes instead of birds. But same general idea. And that was at Harvard? Yeah, I was an undergrad at Harvard, and I was taking Japanese classes, and I was taking East Asian history courses. And then as a non-science major, you had to take some science courses, and one of the ones they offered was this course by Stephen Jay Gould.

And I'd read a lot of his books, so I thought, hey, that's kind of cool. And within half an hour of one of his lectures, I knew that's what I wanted to do. Wow. Talk about, that's quite an inflection point. Well, you and I definitely, perhaps another time of a lot to talk about. I was an East Asian Studies major, undergrad myself, focus on Japanese, and planned on transferring to the neuroscience department, specifically for a number of professors, Barry Jacobs, chief among them, and could not, and I think that animal testing is hugely important, but I could not bring myself to pay the dues in the lab, which involved, I guess they call it perfusing, bleeding to death, i.e. 30 to 40 rats a day.

And I was just like, oh, God, I can't do it. That's, you know, why I work on microbes. Yeah, right. They don't make a lot of noise when you euthanize them. Jessica, what about yourself? How did you come to found uBiome? I mean, what sparked that interest? How did that end up? So I came to this a lot later. I mean, I was always very interested in science. My dad's a

chemist and we used to talk physics and science and chemistry when I was a kid. So I came to, so I was very interested in science as a child, but I didn't sort of, my early science courses was a lot of sort of recreation of early experiments rather than doing your own experiments. So my passion was always for doing, for like learning new things based on science. So I went a totally different route. I studied economics and computer science at Stanford. And then I got a fellowship to go to Oxford to study at the Oxford Internet Institute, and then in other departments at Oxford. And I basically sort of took computer science and economics and put them together to be computational social science. So looking at the mathematics of social networks, kind of taking a different approach to quantifying human behavior. So,

you know, in economics, there's very, there are very specific mathematical approaches that are often used. And I was really frustrated with those. So I thought, okay, let's do something different that's still quantitative and what is now called, you know, big data or data science, but focusing on using different computational methods to understand social science data. And so I was doing a PhD in that. And I was part of a program called Startup Chile, which is a program to go down to Chile, the country, and they give you $40,000 and a visa to Chile so you can become an entrepreneur and start a company in Chile. So I went down there to work on commercializing some of the ideas that I'd had about social networks when I was as part of my PhD. So how you can measure social networks better, how you can determine which ones are

more valuable than other ones. And it was kind of interesting that I met my co-founder who was doing his PhD at UCSF in biophysics. And... This is Zach. This is Zach. Yeah. So Zach was doing his PhD in biophysics at UCSF, working with microbes and doing some very similar types of mathematical techniques to what I was using in social science. And just sort of a plug for social science, this is a rare area where the methods are better in social science in a lot of ways, just because there are many more data points. So if you're looking at data from LinkedIn or Facebook or something, you have millions of data points,

which is, you know, often hard to get in a biological setting. So we just started talking about this. And I just thought, you know, I could take these same skills and apply it to something like genomic data, where you could just have this tremendous impact on human life. And it's led for me into this passion for science and public health that I was always kind of nascent, but I just didn't, I don't know, the academic structures just didn't help me to apply it in a way that felt meaningful to me. And just the idea that you could take the same data science techniques that you used to understand LinkedIn data, which are interesting there, and there's a lot of value to be gained. But the microbiome is this whole other area of human endeavor. There's, you know. It's a whole new organ in the human body that had never been discovered before. And being able to take those same techniques and apply them to something that's sure to yield some impact on humanity was just what I had to do.

How, and without, of course, disclosing the secret sauce and anything you do not want to have public, where do you hope Ubiome to be in three years? What do you – if you could comment on that. Or you can no comment. That's fine too. I mean I think we've been pretty open about what our mission is and what we want to do. And we want to gather – we want to involve the public in science by doing large-scale studies that involve the public. And then to take the products of that research and turn them into useful things that people can use. We will probably not be the people turning them into those things.

So through partnerships with pharmaceutical companies, consumer goods companies, other companies that can actually turn this knowledge into something valuable. This isn't selling people's data. This is sort of taking the insights we learn from the people who are giving us data and then taking those insights and turning them into something meaningful. So that's kind of our focus. So it's something like, this is kind of a terrible example, but I can't think of a better way. It's sort of like Shazam. You know, you use Shazam to like figure out what a song is and then they take that data and they don't sell what songs you like to anyone. They sell what songs are trending and what, you know use Shazam to like figure out what a song is and then they take that data and they don't sell what songs you like to anyone they sell what songs are trending and what you know what songs should you be

writing it's something similar to that we sort of will figure out what is going on in different populations over time through the cooperation with the public and then we'll be able to sort of take those insights and say okay this is clearly useful in this way and helps and give the information to someone who can do who can best make use of it

very cool yeah well i i the reason i backed uh you biome is specifically because i i'm waiting for you guys to develop uh the rock and a pill you know the professional wrestler slash actor so i'm i want to have his microbiome we'll do it for. Since he's like 347 pounds of pure muscle, I assume that will be replicable. It's coming soon. I don't know if you get the rock and the bell, but I think there's just a ton of really interesting and useful things that can be made from our understanding of the microbiome more quickly than in other realms. You know, if you want to take a whole other approach to drug development for cancer, for example, there's just a tremendous amount of research and experimentation that needs

to happen. But we're sort of these natural laboratories for microbes, you know, in terms of us all having different ones that are doing different things. And we can learn from that much more quickly, that's at least our hypothesis, than you can sort of take other approaches to learning about, to developing interesting products from the microbiome. No, definitely.

So I would love to ask a couple of odd questions of you guys. These are a little bit of a shift in gears, but these are what I usually just call the rapid fire questions. But that doesn't mean that the answers have to be rapid fire, but we can try. The first question, this usually isn't the first one that I ask,

but Jonathan, I just love, I love the fire in your belly, so I'm going to ask this one. When you think of the word punchable, whose face is the first one that comes to mind? Jim Watson. Jim Watson? Oh, my. No, this is amazing.

All right, so please elaborate. Well, I don't know if you saw the whole thing about him selling off his Nobel Prize medal recently because he's so impoverished now because the whole world hates him after his racist and sexist commentaries that he made a few years ago associated with the talk. And now he just has to sell that Nobel Prize to raise some funds to buy a painting. To buy a painting? Yeah, to buy a painting. That was one of the things he needed to sell the Nobel Prize for. And, you know, Watson did some interesting stuff for a while, but in all honesty, he's kind of a deplorable character these days,

and I don't think there's anybody that comes to mind quicker than, than him in terms of punchable. Wow. That's an amazing, no, that's a fantastic answer. Uh, the,

the painting must be very, have high nutritional value, uh, you know, uh, or like very thick for, for shelter. Well,

even more amazing, some Russian oligarch bought the medal and is giving it back to him. Wow, that's much more altruistic than I would usually assume Russian oligarchs to be. Go figure. Actually, Jessica, I'll come to you in a second, but Jonathan,

what is the book or the books that you've gifted most often to other people oh i guess i know the exact answer to this i give it to tons of people it's a field guide to the birds of north america by national geographic and i it's like the only book i give to people well that's man you are like these rapid fire questions are really working out here. Jessica, what about you for books? Oh, that's a good question. So I guess it's kind of boring,

but I give Hemingway short stories to a lot of people. I'm a big Hemingway fan. Why are you a big Hemingway fan? Oh, he's just so, such an artisan of the story. Like he is so, his stories are so well-crafted, and it's one of those things where you look at a work of art and you can't exactly figure out how they did it, but it's perfect.

So I admire the craftsmanship so much. Yeah, there's not a lot of bloat in Hemingway's work. No, that is true. Yeah, if you're a Hemingway virgin, The Old Man and the Sea is a pretty good place to start, I think. The short story is also fantastic. Jonathan, do you have any particular morning rituals? What does the first hour of your day or two hours of your day look like?

Is it pretty standardized? It's very standardized. My wife probably gets up first, and we have about an hour before our kids get up. And usually we make coffee on a stovetop coffee maker. And we drink coffee. And we sometimes sit there and space out. And sometimes we talk about the plan for the day.

And usually our cat comes over and hangs out with us, and that's what we do for an hour. When do you wake up? Her alarm goes off at like 5.55 in the morning. I'm sometimes up before that, sometimes up after that, and we have about an hour before the kids get up. Now, okay,, this is amazing. I may have a soul connection with your wife, which sounds weird to say since we don't know each other that well.

Why 5.55? I don't know. She really likes to have time to veg out and to think and to process before dealing with the ritual of getting the kids fed and off to school. And I don't think an hour was enough. So an hour and five minutes is like the bonus time. Wow. So 5.55, I don't know if I've talked about this publicly. I won't digress too far. But so 5.55 PM was the time that I finished editing a book I wrote called The 4-Hour Body, which was a monster. I mean, it was almost 600 pages after cutting 250.

And it was the exact time that I finished my last line of editing in the book and was ready to mail off the final thing. So I always take a screenshot on my iPhone whenever it's 555 because it's sort of my good luck omen. Anyway, that's amazing. That's awesome. Give a high five to your wife. I will take screenshots now when I get woken up by the alarm.

It's going to be a lot of screenshots. I'm sure I won't be able to think well enough to take more than a couple. Not photos, screenshots. Now, coming from a family of scientists, how do you think about parenting differently from your non-scientist friends, if at all? Yeah, I mean, I'm not sure at all. You know, we went through when our first kid was born, our daughter, we went through the, you know, like read a bunch of books like they're going to tell you exactly what you're supposed to do related to parenting. And most of it is just, you know, something that worked for one person. And, you know, it didn't necessarily work for us. And again, it goes back to that rule thing. If you follow those books as a rule, they're horrible. If you follow them as a constraint and guideline, they're pretty good. So I think my wife's also a scientist. She hasn't been

working in the lab recently. We say she's a child developmental biologist. But so we're both scientists and we have a lot of scientists in our background, but we try not either force science onto our kids or obsess about scientific approaches to everything. We're much more sort of holistic about how we deal with the kids and holistic in the sense that we try to, you know, talk to each other about things and think of, you know, common sense approaches, as opposed to digging into every possible scientific study that could have been done. Right, right. And it also brings up a good point, just the books on parenting comment.

This is a good example of sort of where media, I think, can get things totally ass backwards, where they might say, well, we looked at the data, and you had 100 people who read you had a hundred people who read parenting books and a hundred people who didn't. And the people who read parenting books turned out to be better parents. Therefore parenting books make you better parents. And it's like, well, it could just be that the people who are proactive enough to actually go buy books on parenting are going to end up being the better parents anyway, because they care more and so on and so forth. So yeah, that's, that seems to be the, the, the feedback I get from a lot of my

friends who are parents. I am not yet, but I'm certainly looking for the cliff notes to the extent that I can. One more question for you, Jonathan, and then I'm going to start raining questions on Jessica for a bit. But is there a particular defining moment of your childhood that you can think of? Or was there a defining moment in your childhood that helped mold you into who you are? I mean, I think, you know, we've already talked about one, which was the, you know, being moments away from probably going into a coma and dying from diabetes, which really had a massive impact on lots of things. But I think unquestionably, I can tell you one very specific moment that had a huge impact on me as a child. When I was almost 10 years old or just 10 years old, we went to Kenya to visit my uncle who was studying baboons there for his PhD in anthropology. He was doing fieldwork in Amboseli. And we went camping

in the middle of the Maasai Mara and other parts of Kenya, you know, with lions wandering around outside. And one day we were driving through the savannah and my uncle said, that's weird, and pointed way off in the distance to this gazelle that was doing something strange. And we stopped the car and waited. And slowly, over a period of maybe 15 minutes, a cheetah came from over where that gazelle was and walked about five feet from our car. And then we watched it do the cheetah sprint. It didn't catch the gazelle, but it did the full 60-mile-per-hour sprint. It didn't catch the gazelle, but it did the full, you know, 60 mile per hour sprint. And

that moment was so awe-inspiring and transformative to me to just think more about the natural world. I mean, I was kind of into birds then, but I wasn't really thinking about it. But that just seeing the dynamic system in the savannah and seeing this incredibly beautiful, graceful predator coming out of nowhere, that I still remember that moment. Wow, that sounds incredible. That's an amazing story. What time of day was that? It was in the afternoon. I don't know exactly when. I was just painting the picture in my mind because it's just like… It was incredible.

And by the way, as an aside, we're now looking into doing studies of the cheetah microbiome because I have to return to my roots. I was hoping you would say that you've adopted a cheetah and put a saddle on it, like Harold and Kumar go to White Castle. Yeah, that too, but I can't tell people about that. Right, yeah. Legal only in several states, not all. Jessica, when you think of the word successful, who is the first person who comes to mind for you? Oh, wow. That's a really good question. There's so many different ways to be successful.

I think, so no particular name comes to mind, but what I really admire is when people have come a long distance from where they used to be to where they are. And I think sometimes the people who've done that haven't come very far on a global standard, but they've come very far from where they used to be. So I always love reading stories about people who were in prison and then totally changed their lives, or people who came from really modest circumstances and really did amazing things with it. So I think for me, thinking about that distance that people travel is what makes them successful. Okay. No, I mean, that's a good answer. I think that, you know, I guess it's about

Hurricane Carter. I mean, there are a lot of, of is, I mean, it's a good answer. I think that, you know, I guess it's what Hurricane Carter, I mean, there are a lot of, of course, many people who can, who are inspiring in that sense. Who do you, who do you aspire to be like or to emulate as a founder or CEO? Oh, that's a great question. Oh, wow. Um, so I'm not, I,, it's a confession, I suppose. I'm not a big worshiper of the sort of canonical Silicon Valley CEOs, you know, Steve Jobs and Larry Ellison and, you know, even Sergey Brin and Larry Page. I think a lot of these things are sort of, you know, six-sigma events that happened in a particular place in a particular time and sort of slavishly saying, well, Steve Jobs did it, so it's a great idea for us, is kind of not the best way to go.

I think the people that I try to emulate are people that are one step past where I am, not people that are 10 steps past where I am. So they're probably people you wouldn't necessarily know, but they've kind of gone to the next stage where I aspire to be, and then the next stage after that. That's fine. Any particular names? No names are sort of gone to the next stage where I aspire to be and then the next stage after that. That's fine. Any particular names?

We'd love to hear some. No names are sort of coming to mind. I do a lot of reading and talking to people, but no names are coming to mind. At least no one who I would think it would be okay for me to name them on a podcast. That's all right. How do you find those people? That's a good question. I find some of them through our investors. We find people that have sort of been funded at the next stage or who have done the things

that we're trying to do. I find them at conferences. I also just sort of find them through researching online and trying to think, you know, who has done the thing that I'm just about to try to do and, or maybe the thing that comes right after that and try to talk to them. I think you were talking about superpowers earlier, and I think if I have any sort of superpower, it's sort of that figuring out who is doing the next thing

and being able to talk with them and learn what they know. That's a good superpower. What are the questions you like to ask such people? Oh, so I love to ask how things were done. I think a lot of these things, especially when they're reported in the media, are like so-and-so is an amazing CEO and they did this crazy thing. But when you actually find out how it happened, it's because their college roommate was doing it also or their professor told them how to do it or there's some trick that they know that nobody else knows.

So I like to ask sort of questions around what that trick is. Like how exactly did this happen? Where did you first find out about it? What happened specifically? And I think that's sort of how questions are really important. I also like to ask values questions because I think that leads to a lot of interesting answers about what was fundamental to what happened as opposed to what was merely incidental. What would be an example of that? Oh, so, um, so there's a CEO that I, um, sometimes talk to who's a, has a, a company

that has a really strong culture. Um, and I ask a lot about what, what was really fundamental in dry, like what choices did they, what things did they not do that they could have done that perhaps they even wanted to do that they didn't do in order to have the culture that they have? So what was the – what things cost them? What was the sort of – where was there some sort of hard choice? What sacrifices did they make? Sacrifice, exactly. Well, what sacrifices did they make sounds a little bit cliche. It's like, oh, well, I didn't go to the beach or I didn't spend time with my cat or whatever. I'm thinking about more in terms of sacrifice.

It was a dog culture. You got to choose sides. Exactly. I'm thinking more about things like what decision did it hurt you to make, but you're glad you made it? Can you give an example of any of the answers? Oh, yeah. So I think one particular answer is sort of trusting the people around you in ways you might not necessarily think of to do. Like what? Oh, well, in terms of just having a company culture that's very open and very trusting of the people that you work with. For example, I mean, this is something that we try to do at your biome.

Like we have, you know, a lead day scientist we hired. He's a theoretical physicist. He's, you know, just got out of his postdoc. And he's never managed a team. He's never written code. He's never done any of these things. But we have him doing all kinds of stuff. You know, he's hiring people. He's doing all kinds of things just because he wants to and he can. So I think think there's sort of a profound respect that I have and that I learned through these conversations based on letting people do the things that they want to do if they seem like they can do them. We can dig into that maybe in a round two. That's a big subject. Jonathan, do you have any favorite documentaries or movies that come to mind? If you want nonfiction like documentaries, I, in terms of movies, I've been watching over and over

Shackleton movie. It was like a made for TV or cable movie about Shackleton. It's incredible. It's just, you know, the best thing out there that is about the Shackleton story that currently exists right now. What do you like about it, this particular coverage or story? Well, I mean, the story itself is remarkable in so many ways. I mean, I'm really interested in exploration. So, you know, the great stories of all the explorers over time, I read a lot of and I, you know, I think the Shackleton story obviously is pretty incredible because, you know, they were setting out to do one particular thing.

It didn't work out the way they wanted it. And despite getting stranded on the ice and, you know, having difficult circumstances. And over two years, even though they sort of fought with each other, they, you know, they did mostly stick together. And it's just this, this amazing sort of story of human spirit and persistence and exploration. And I read a lot of these stories about, you know, Antarctica and Arctic exploration. And I read a lot of these stories about, you know, Antarctica and Arctic exploration. And prior to that, you know, exploring the world around us and the Shackleton one just is pretty incredible. So this is weird, because I have a searchlight for those kinds of exploration stories. I haven't watched the Shackleton documentary, but I love sort of the,

you know, Beryl Markham and Amelia Earhart and that whole sort of, you know, early flight stories. I haven't watched the Stack Open documentary, but I love sort of the Beryl Markham and Amelia Earhart and that whole sort of early flight stories. I'm kind of a geek about those. I want to throw out a plug for a movie. I don't know if you've seen this, Tim. Have you seen the movie The Edge with Anthony Hopkins? No, I have not. Oh, wait a second. Is this about the Indian motorcycle

speed test? No. So this is about a... anthony hopkins is like this sort of this perfect character he's a he's a billionaire scientist who's exploring the arctic right so it's kind of this like sort of out there setup where he's you know this billionaire scientist who doesn't spend enough time in the real world and he gets lost in the arctic and there's all sorts of interesting subplots but basically he needs to find his way back to civilization and kill this bear that's trying to kill him oh i saw a i saw a trailer for this okay so this was never like this movie is not famous like i don't know why i mean it has anthony

hopkins and alec baldwin and l mcpherson in it so you think it would be something everyone's seen but no one has seen this movie and it is my absolute favorite movie it is just sort of this great story where not only does he sort of survive by his wits and you know get you know defeat nature in a way he also his companions are not on his side of not to spoil it yeah no don't spoil it i'll watch it and they are they're not on his side and he manages to save them too so there's this sort of this altruism to it as well. I'll watch that. I'll probably watch that this evening.

And Jonathan, I wanted to, I have, I've not seen the documentary on Shackleton, but the, uh, one of my favorite things, maybe my favorite thing, just not knowing much about that story. Uh, one of my favorite things about it is the classified ad and I'm looking at a copy of it and the is the classified ad and I'm looking at a copy of it and the, the classified ad, this is what Shackleton used to recruit people to help in this journey is headline men wanted. And then the,

the subhead is for hazardous journey, small wages, bitter, cold, long months of complete darkness, constant danger, safe return, doubtful honor and recognition in case of success.

And then his name and address, just so amazing. I feel like most job descriptions should have disclaimers like that. And the turnover would be a lot lower. Sorry, I was just going to say, so one of our investors, someone you know, Tim, loves that ad and said we should put that in all of our job ads. Oh, I totally agree. Oh, man. Jonathan, where were you going?

I was just going to say, in the movie, Kenneth Branagh is Shackleton, and there's this great scene where someone is coming in with that advertisement to, you know, apply for the job. So it's just completely perfect. Well, I heard that he was inundated with applications. I don't know if that's true or not. They were drowning, and they literally got, you know, they had to hire was inundated with applications. I don't know if that's true or not. They were drowning and they literally got – they had to hire people to go through the mail because they got so many applications. That's so awesome. That's great. And the great thing about that disclosure is that they can always pull out the, well, I told you so.

You can't really complain about the darkness. I fucking told you in the classified. I mean this wasn't a hidden risk. Jonathan, if you could change or improve one thing about yourself, what would it be? Better organization. I'm not really good at planning things or keeping everything organized. Do you think that the hatred of rules is related to that? That's my plan a lot, Jonathan. Should I lie down on the couch in my hotel room now?

No, no. I'm not qualified. I think that there's a very strong correlation there. Whether it's causal or not, I don't know. But yeah, I mean, I think I, you know, I do a really good job with getting things to happen most of the time. But I could definitely use much better, much more effort on, you know, a personal assistant or some type of planning. So, okay. Now this is, okay. So I don't let journalists follow me for what they want to be a typical day really ever because I find people expect me to be this sort of paragon of efficiency and I run my life like Spock and it's just this incredible sort of Swiss watch of productivity. And I'm like, if you came and watched me, you would

just ask yourself all day, what the fuck is this guy doing? And it's, but despite all of my flaws, I get a fair amount done. And it's for, I mean, the reasons that I could speculate and talk about, and I have talked about ad nauseum, so I won't do it now. But you, Jonathan, you've done a huge amount, accomplished a huge amount. So what allows you maybe it is the lack of the rules. I have a big picture of what's happening in my lab and in the work I want to do and in the projects I want to do. And I'm not always obsessing with, you know, am I following the right path for a professor or am I applying for the right jobs or am I submitting to the right journal? I do what I want to do. And it's worked out really, really well for me. And I think that in research, I know a lot of colleagues who spend a lot of time worrying about what they're supposed to do as opposed to what they want to do. And so I think because I don't spend a lot of time

thinking about what I'm supposed to do, it works out a lot of the time that I get a lot done because I'm doing the things I love and excited about, and I never worry about what I'm supposed to do. But I confess, things slip through the cracks with that approach. And most of the time, it doesn't matter, but every once in a while, it does. No, I like this. This reminds me of something that I read by one of my favorite writers, Neil Gaiman, who's a fiction writer. And he gave a commencement speech, and I think it was simply in this particular commencement about sort of the big picture of moving closer to or further away from the mountain, which is this major goal he had of, I believe it was just being a full-time writer. And a lot slipped through the cracks, but because he had that one North Star, it sounds like, as you do with, say, the sort of overarching goals of the, um, the lab or otherwise he, he's been able to create this incredible career, even though a lot has fallen through the cracks.

Um, so speaking of commencements, uh, on a related note, and then I'll, I'll, I'll let us wrap up. This has been a lot of fun and I, I want to be respectful of both your, uh, your evenings. Jessica, if you were giving a few pieces of advice to your 20-year-old self, what would the advice be? And Jonathan, I'll ask you the same as well after this. So I think my advice to my 20-year-old self would be about confidence. I mean, I think I've learned so much through working on my PhD, through starting this company. I've just sort of gained such a broader perspective. And I think I just didn't have confidence in myself and in what I could do and in sort of the level to which I could be pushed and still excel. And I think I would just tell my 20-year-old self to just

not be so afraid of trying things. I think that would really, that's the number one piece of advice. And I think the second thing would be to really think very broadly about what's possible. That's kind of related, but just sort of not only think you can do it, but think about that there are many things possible in the world to do that I don't think I thought of when I was 20. And all the sort of standard like buy this stock or- Yeah, buy Apple, right? Right, exactly, buy Apple. What were you so, why did you lack confidence? Why were you intimidated?

I thought about this a lot. I mean, I think that some of this is sort of that traditional female sort of stuff where like, and I see this all the time. And when I see it in people, I always comment about it because I kind of make a point of it. Maybe I'm annoying about it. But I was just talking to someone today who was like, well, this know if I can do that. Maybe it'll be, you know, maybe I should just wait and ask them if it's okay. And I'm like, no, no, no. Women wait and ask. Men just go do it and then apologize for it later. And I think it's just like, it's true. There's sort of this like very female like, oh, wait and you'll be rewarded.

Like that CEO of Microsoft was saying, women should just wait and not ask for raises and then karma will give them money. And I just feel like he actually said that. And I think we were just socialized to believe that. So I think that's a big part of it. But I think another part of it was just, I don't know. I think another part of it may have been sort of socioeconomic.

I think there's sort of this like upper middle class, you know, feeling of power that I learned at Stanford that I didn't know before that. And there's sort of this sense that you can, you know, feeling of power that I learned at Stanford that I didn't know before that. And there's sort of this sense that you can get close to the seat of power. I remember when I when I first came to Stanford, and I just, you know, you meet people that you read about in the news. I just didn't know anyone before who'd ever met anyone who'd been in the news. And you know, go to a talk, and it's like, the Secretary of Defense or something, or it's, you know, that, you know,

it's Steven Pinker, it's somebody that's just like, you've read their books, but the idea that these are actually real people who were not perfect, and didn't do everything perfectly. I think I, as a child, I sort of imbibed this very, like, you know, my grandparents were immigrants after the Holocaust, and my parents sort of grew up in that kind of milieu in New York. And when I sort of, there's always this idea milieu in New York. And when I sort of, there's always this idea that if you're perfect, if you work hard, and you're absolutely perfect, you too can succeed. And when I met people who are like the most successful people in the world, and they had lots of problems, and were also very anxious about lots of things, I thought, okay, you know, I could be one of those people. Right? You're like, Oh, okay, I get it. These

are human problems, not exactly. I didn't know that growing up. So that was a big revelation for me. And I want to just underscore one thing you said. And it's always a danger for me to say this because I look like American History X. So it's a sensitive subject. But I was having a conversation once with a very, very, very successful female executive. And the topic, this was a group conversation among friends and the cop, the topic came up about salary discrepancies and her thought, and I'm not saying this is the only, certainly not the only perspective, but she was massively, I mean, she makes millions and millions of dollars a year. And she said, the reason women make less oftentimes is because they don't ask for more. Yeah. Studies have shown that. That's not just her.

Yeah. And so, yeah, the asking for forgiveness rather than asking for permission, I think, is a really important one. Jonathan, what do you... Oh, I'm sorry. Go ahead. Didn't mean to cut you off. I was just going to say, I mean, this is very controversial because, you know, Sheryl Sandberg's point about leaning in, but I think she's absolutely right. There are all sorts of structural inequalities and all those things are all true. But being able to just not stop yourself is at least a first order approach that you can take where other people may stop you, but at least don't stop yourself.

Right, right. No, absolutely. Jonathan, what advice would you give your 20-year-old self? I would tell myself to bank all my fecal samples. With your biomes, obviously. And they'd be like, what? Like in an ice cube tray? How do I do that? So weird. No, you know, I mean, just like I don't plan things very well, I also am not very retrospective in thinking. But I mean, I think that the thing

that I wish I had done more of and that I think would be, you know, really good in general is to trust good people and ask them advice. I mean, I have asked people advice over the years. And when there are people that I really trust and people that seem to be good human beings, that advice has actually been really good a lot of the time.

And I don't think I've done that enough. I think that a lot of the time I try to work things out in my head through some logical flowchart or because I'm so damn smart. I think asking for help from the right people is a really good thing. And I wish I had done that more. And related to that, something I also wish I had done more, and I try to do much more now, is to thank people who help you.

There's lots of people along the way in life who do something small or something big who have helped me and help everybody else in a lot of ways. And, you know, in science, we stand on the shoulders of others. And, you know, it doesn't hurt to thank those people. That's great advice. Well, on that note, thank you both so much for taking this time. This was a really enjoyable conversation for me. And I hope that that's true for both of you as well. How can, how can people learn more about what you are up to? And I'll let,

we'll go back to Jessica here. Jessica, where can people learn more about everything that you're up to? Yeah. So as far as you buy them goes, you go to you buy them.com. That's what the U with the U. Yes. I should spell that. It's U B I O M E.com. Um, so just go to you buy them.com. There's sort of, there's interesting information about what we're doing. Our blog is there. You

can also purchase kits to better understand your own microbiome, um, and all sorts of interesting stuff. Just, just mailed one off myself today. Thank you. Back to you, yes. We look forward to receiving your proof. And are you on Twitter? Any other social media outlets? Oh, yeah. So I'm on Twitter at Jessica Richman.

So that's just my name, J-E-S-S-I-C-A-R-I-C-H-M-A-N, like a wealthy man. And Ubiome is also on Twitter at Ubiome. Very cool. And Jonathan? Everything associated with phylogenomics, that's my Twitter handle. My personal blog is phylogenomics at blogspot. My lab website is a phylogenomics WordPress site. So the best way to find out about me is probably to just google phylogenomics p-h-y-l-o-g-e-n-o-m-i-c-s and then most of the stuff that comes up is something i've done awesome well guys this was a blast i really appreciate it have a wonderful weekend and uh to be continued hopefully yeah you

too thanks so much for having me on all right thank you very much thanks guys bye bye okay