184. The Multiverse of Microbes: Henry Lee on Building Cultivarium and Training with Titans

Henry [00:00:00] But honestly, developmentally, here's what I think about where we are in terms of computing biology. We are still children playing with shapes. All of protein engineering is playing with shape

Erum Hey, Carl. How's it going?

Karl Things are going great. Doesn't it feel like summery, Rum?

Erum Yes. Well, Memorial Day just happened, and for sure, even though the temperatures are going up and down, still not sure how it's gonna land. Are we gonna have a super hot summer or a nice summer? It doesn't matter. It's summer.

Erum Who cares?

Karl Exactly. I feel like people's moods have lifted. I, as you know, was in Ithaca last week to celebrate my son Tomas's graduation, from Cornell. He graduated with a degree in environmental engineering, so congratulations, Tomas. And,

Karl for Tomas's graduation, they did two ceremonies. One was really nice in the wrestling auditorium. There was maybe, like, 100, 150 graduates from biomedical engineering and environmental [00:01:00] engineering together. And then the next day was, the big ceremony for all the different colleges, and that was held in the stadium, and we got rained on the whole time.

Karl So welcome to pre-summer.

Erum Yeah. Well, you know, anytime it rains on a, great celebration, it means it's good luck, right? So-

Karl Yeah. ...

Erum there you go, Tomas. Congratulations, and excited to see what he does. there's a lot of relationship between biotech and environmental engineering, so we'll have to see how Tomas's career pans out.

Erum But we can certainly, steer him in the right direction, the direction of biotech.

Karl Well, so what's interesting is the environmental engineering students and the biomedical engineering students graduate together. Yeah. So there isprobably some overlap there between them. And, he's going on to do a master's degree in a program that is aeronautical and mechanical engineering, I think.

Karl I might get it wrong. Sorry, Tomas.you did something super cool last night. You went to go see this Radiohead immersive experience. What does that have [00:02:00] to do with growing everything?

Erum Well, first of all, I will make those connections because that's how I do.

Erum I just jazz it up and, spin things around. But I will just say that I love Radiohead. I've loved them since I was a high school student, so you guys can get a glimpse of who I am from Radiohead. Like, that is the soundtrack of my life. It's a bit melancholy, not really uplifting, so I do have other music that I listen for that.

Erum But it is amazing, this experience was in the Brooklyn Navy Yard. So for those that don't know what that's like, it's a, industrial area that has some old school buildings. What happened for Radiohead was Thom Yorke, who's the lead singer and the producer and creator of Radiohead, and some other artists came together and They took this old space and they put up an exhibit, and then this immersive experience which was four large screen TVs That had spatial audio speakers, and then they ran this, one-hour music video for the album called Kid Amnesia or Kid A, Kid [00:03:00] Amnesia, I always forget which one it is.

Erum but I will say that It was very moving, and You could see how there was an evolution from Thom Yorke's early career to now, and how there's this mix of media and innovation in sound and audio, and how each of the songs were more elevated.

Erum And then this music video was just so bizarre. You have to watch it, but There's these, unique creatures and these unique worlds, and then the music of Radiohead in the background. But it was a commentary on society and who we are as individuals. And before the music video started, it's like,

Erum like, very, like, "Just relax and watch this." but on the screen, it had a timer, and it was like, "Lay down," everything, and But just slow down. Slow down. Slow down." And To me, it was very, emotional to, to hear that and see that because I'm just moving so fast all the time.

Erum we're always moving fast. I just feel like taking the time to, just absorb this, crazy, like, abstract [00:04:00] but so relatable, music experience was, good for my soul and therapeutic in a way.

Karl Yeah, I mean it, sounds great. I was telling you before, I'm a huge Thom Yorke fan. I feel like he's been a gateway into a lot of experimental, and ambient music. He seems like he was a huge supporter of Warp Records early n- the mid-'90s, early 2000s. Probably introduced a lot of people to Aphex Twin.

Karl and that opens up a lot of other kind of experimental music. It sounds like a great experience. I've also been talking about going to the movies a lot, so I've seen some weird movies in the last week. but, I think we can save those for later.

Karl let's get into some biotech tea.

Erum Oh my gosh, yeah. So you shared this with me. You shared this Intelligencer article, which is part of New York Magazine, about Kathy Tai, who is the co-founder or was a co-founder of, a biotech company that [00:05:00] was, using gene editing to change up embryos for making unique organisms, and she co-founded it with Josie Zaner, who, had a company that shipped CRISPR kits to anyone, and that company was called The Odin.

Erum Josie Zaner herself is a very interesting person. But this article, wow, Carl, like finally we get to talk about some gossip in biotech. And Kathy she's known as Biotech Barbie or maybe she's self-acclaimed Biotech Barbie, but, I really found this so interesting 'cause Kathy she is really good at playing the piano, and like it started off that she, rented out Carnegie Hall for her birthday.

Erum Which

Karl is crazy, yeah.

Erum Yeah. And had some other performers but then she performed on stage in this beautiful gown. what'd you take away from this? I mean, there's so much to unpack here.

Karl there was a lot, but I, think what I, took away was what she's doing fits into the zeitgeist on the longevity side because what she's trying to [00:06:00] do is, engineer embryos before they're born.

Karl So for intelligence, for physical traits, this kind of thing. And you pointed out that she had been married to He Jiankui, the Chinese researcher that was arrested after he CRISPR-edited, twins in the womb so that they would be resistant to the HIV virus. So really interesting kind of lineage. And there were some points in the, article where it talks about Kathy's, work where she's, debating ethicists and, she's just kind of out there talking to a lot of people.

Karl It's gonna be interesting to see where she ends up. I think she might be someone who we want to get on the podcast, same with Josie. and, I think if you are able to access the article, we'll put a link in the show notes. It is behind a paywall, but the comments themselves make it worth reading the article because a lot of them are like, "Why is this in New York Magazine?"

Karl Others are like, "This wouldn't be in New York Magazine if this person didn't have money." or If you're able to, rent out Carnegie Hall, that already says a lot about you. So I think, more Biotech Tea is welcome, and [00:07:00] we're gonna take it apart when we can.

Erum Yeah. If anyone knows, I mean, like, just out of curiosity, because Josie Zayner, and I didn't know much about Kathy Tai until, this article.

Erum But sounds like she's a personality, Josie's a personality, and both of them co-founding a company and now not working together. I want to watch that on Netflix. Like, what is this documentary about how both of them came up into this world of biotech, met each other, tried to create this company where they're trying to make unicorns and dragons, like literally was like their mission to do that, and I'm sure, Josie's still on it and maybe Ca- uh, Kathy's still on it.

Erum both still focusing on engineering embryos. So it's just such a bizarre real story that we need to c- continue following. I had seen Josie Zaner a couple times at events, and I was like, "You gotta come on the pod." And, they were like, not right now. It's a crazy time," and I couldn't imagine starting a company and, but this is your chance, Josie, to come [00:08:00] on, share your side of the story.

Karl We wanted to get you on, and now we want to get Kathy on as well, so.

Erum Yeah, who's first? Let's

Karl see. Yeah. Exactly. So Iram, have you heard of this video game called Stray?

Erum I heard it just a really quick, you showed me, a trailer, but I am so excited about this.

Karl Okay, so I have to admit, I haven't played it, and it's not a new game.

Karl I think it came out at the end of 20- 25. but it just showed up in my feeds, and it's a story about a cat that's trying to get home, but it could also be looked at as a pop culture entry into a conversation our, industry or the synthetic biology, biotech industry needs to be having because it's talking about commercialization versus safety in bioremediation with engineered microbes

Erum What?

Karl Yeah. So apparently, while this cat is trying to find its way home, the game dramatizes the exact failure that synthetic biologists or biotechnologists worry about, which is that their organisms get [00:09:00] out into the world. And in this case, it's a plastic-eating bacteria that over time, the kill switches on those bacteria degrade, and they find a new way of living, and, the system that they're living in, which is sealed, loses its check.

Karl So I think we both need to check out this game and then come back and trade notes on it.

Erum Yes. Oh my gosh. I'm so excited for this because, we are looking to get biology more into the mainstream so people understand what's possible. And games, video games in particular, cartoons, shows, just all of that entertainment, edutainment if you want to call it that, so important for us to at least imagine what's possible and then, think about what we can build.

Erum So if you want to create these plastic-eating, bacteria, how do we do that? So then it's a matter of just engineering or, like, reverse engineering or this reverse thinking of how do we get started, and [00:10:00] that's when the journey starts. So I love this. I mean, the Nintendo Switch, right? this is where the game- The

Karl Nintendo Switch,

Karl Yeah. And what I like is that it's world building, it addresses this idea that even if you put a kill switch into a bacteria, it's going to evolve ar- under evolutionary pressure, and so we don't really know what the long-term consequences are.

Karl People are talking about this actively. and I think it's a very important conversation to have, so-

Erum Yeah.

Karl to check it out. Yeah.

Erum Yeah. And this conversation isn't explicit, right? It's implicit in this other story. that is happening, which I think is a very great way of talking about complex, narratives or complex science, is that, you have a bigger story that's playing out that has problems and situations, but can be resolved or exacerbated by biology depending on, what the storylines are.

Erum And you know what? It's all coming back to the one thing that brings us all together in the digital landscape, and that's cats. So [00:11:00] Yeah. And in the, physical world, we all just love cats. They're just so interesting to follow. I don't have a cat. I want a cat. I have to talk to my husband about that.

Erum we do have a small place here in, Brooklyn, so it might not be, really nice for a cat. But you know what? I'm saying that, and I've talked to other friends that have cats in Brooklyn, so they would probably be like, "Shame, shame, Iram. No, you can't use that as an excuse." but cool. All right. We've got link in the show notes.

Erum If anyone's playing this game, please comment and tell us what you think about it.

Karl Okay, and so before we get into the pod, I just want to do a quick shout-out to Erica, de Benedictis of Pioneer Labs, who was just here in New York City. I got to spend about an hour and a half with her walking around, Dumbo in Brooklyn.

Karl Iram, you couldn't make it. I'm super sorry, but it was just nice to see Erica in person, congratulate her on having a baby. And, to get caught up on what she's doing at Pioneer, with building the chassis for, sending microbes up to Mars.

Karl And that said, we are going to have an interview with Lynn [00:12:00] Rothschild of NASA Ames, who is also a pioneer in extremophiles and talks a lot about space. So we're super excited to get her on the pod, and we're excited to share that with you, our audience, when we do that.

Erum Yeah, absolutely. Oh, God, I love space.

Erum I'm so sad I missed that. can't wait to talk to Lynn. There's so much happening in the world of space. There's a lot of space drama, space tea hopefully that we can spill on that episode. But let's talk about our episode today. I'm so excited for this because we have our dear friend Henry Lee of Cultivarium joining us today, and it's about time, right, Carl?

Karl Yeah, it's been a while. So we've known Henry and Cultivarium and then, Henry's partner, Nili Ostroff, for I would say probably four years. We did some nice work with, Cultivarium when they first started on their messaging and recruitment and did a lot of work with them, and then we had Nili on the pod, which was great.

Karl Cultivarium started as [00:13:00] a focus research organization. I think the mission was really to make non-model organisms, more easy to work with, and Henry will talk about that. But then as they've evolved, they've become a frontier research contractor, which Henry will explain what that is. So I think with that, let's let Henry take it away.

Karl Henry Lee of Cultivarium, we are so happy to bring you onto the Grow Everything podcast.

Henry Thanks for having me. Great to see friends, Karl and Erum

Karl let's start off by getting some background on who Henry Lee is. Your background spans, electrical engineering, signal processing, synthetic biology, and bioengineering.

Karl What was the moment you said to yourself, "I wanna focus not on model organisms, but on the vast microbial dark matter, the stuff that most scientists ignore"?

Henry what was really fun about that transition is I grew up around computers, I [00:14:00] grew up building circuits, and that was really great trying to figure out how you program bits, right?

Henry And right about when I was graduating undergrad, a bunch of professors were talking about how cells were like computers and how genes are parts of circuits, and I thought, "Wow, I gotta really go check that out." And the funny part about doing this is, I just had no idea what the jargon was. I didn't know what a gene was.

Henry I didn't know what an operon was. I spent, six, nine months trying to figure out what anybody was talking about in lab meetings. And so it was a really big transition of trying to understand what biology, what the biology lingo was. And the cool part about it, and the very humbling part about it, is that you can use this metaphor of cells are like computers, they're programmable But that's about as far as you can take that metaphor.

Henry You need a whole different approach to thinking about how predictable things [00:15:00] are, how noisy things are, and that was a really big challenge and a long road for me to get humbled by biology in order to contribute in a way that was meaningful. And you had followed up with one last question, which is, what is it about non-model organisms?

Henry What is it about dark matter? To me, it's all non-model organisms. It's all dark matter. every different organism has its own particular needs, has its own particular, nuances. The way that I describe it is imagine you're trying to plant something new in your garden. Well, you need to know the specifications of how much light it needs or how much space it needs, when does it flower, what is the growth cycle.

Henry And so this is really well characterized when you go to a nursery, when you go to a seed bank, and maybe we get a little sheet, right, that tells you all of these characteristics. And it turns out when you look at the organisms all around us in the environment, there is not such a sheet. So oftentimes we're [00:16:00] stuck trying to figure things out, by ourselves, and that's what we do at Cultivarium.

Henry We try to figure out what those specifications are and how do we actually bring those into our garden of organisms to study and engineer.

Erum Wow. Yeah. And can you just tell us a little bit more and just to paint the picture because our audience is broad, and so what is a model organism and a non-model organism, just to clear that up for us?

Henry that's a great prompt. The science today runs a lot on a few organisms that we call model organisms. So those are the ones where we can go and get it off the shelf, and we know pretty much how they behave. Popular ones are Saccharomyces cerevisiae, which people have been using for millennia.

Henry That is in your bread, in your beer. Those are used to brew things, right? So it turns sugar into alcohol that we all enjoy. The other [00:17:00] one that's really often used that most people have heard about is Escherichia coli or E. coli. Those of us that used to eat at Jack in the Box might remember that's when it really broke into the popular news where it is a pathogen.

Henry some of them are, but not all of them are. And the model organisms that we use in science are basically ones that are by convenience. We can get them through human processes. We can grow them easily, and so that becomes a really nice, organism that we can play with in the lab. We can grow lots of them.

Henry We can take them apart. We can, try to put them in different conditions. They're fairly hardy Now, model organisms have given us awesome biotechnologies, awesome genetics. We're able to make a lot of different products and chemicals out there in the form of molecules today. But what we're running into is that oftentimes in this modern day and age, we want a more exotic molecule.

Henry We want [00:18:00] more, production out of less input. We want more intensive processes. So one way to meet those needs is to say, "Okay, well, what else exists in nature?" If you have a different organism that we call non-models, so not the ones that we've studied for fifty, sixty, almost a hundred years, they might be able to take what otherwise humans would have generated and thrown away as waste, and they are wired already to be able to take that waste and use that as food.

Henry And so one way you can think about that is they convert waste to value So that's one set of properties that you could get from non-model organisms. There are other ones that are really interesting and fantastical. So there's one called Radiodurans. It is really resistant to nuclear radiation. So that in itself is interesting.

Henry why does it do that? And some of the interest there is, well, even though it gets all this radiation, it's really good at repairing its DNA. How [00:19:00] does it do that? And how can we use those learnings for better health for us so that we can protect against DNA damage that might lead to all sorts of disease, including cancer.

Henry So these non-model organisms, however, just have not had a lot of people dedicate their lives to studying it. And so what that means is we kind of know they exist, we kind of know they do a cool thing, but beyond that, when we try to bring them into the lab, we don't know exactly what conditions they need to grow, what nutrients they need.

Henry We don't know exactly how to turn their genes on and off, because unlike the E. coli and unlike the Saccharomyces cerevisiae baker's yeast, we just haven't had that amount of scientific effort put into, developing those methods. So hopefully that gives a sense of the discrimination between model and non-model.

Henry But I'll, I'll even give you, the why we're so excited about it is because, [00:20:00] there's about three to five different model organisms out there in the world that people, that scientists are really studying and using all the time. There's millions to a trillion different organisms out there in the environment.

Henry So, to say that we have barely begun to scratch the surface is barely starting to scratch the surface of that surface. So there's just so much out there that we haven't looked at where there's just a lot of opportunity. so if you've heard of CRISPR, right? That came from a non-model yogurt-dwelling bacteria, amongst other things.

Henry So there's just so much out there that we can tap, and it's important for us to develop the systems and the methods to be able to go out and study those things.

Erum and for this conversation, we're strictly focusing on microorganisms because there are, multicellular, model organisms like zebrafish or C.

Erum elegans. That's a separate conversation, unless you want to talk a little bit about that.

Henry I love all sorts of [00:21:00] organisms. So, let's see where this conversation goes.

Erum Okay, let's do it. All right. And it's completely open. So we've had your co-founder, Nili, on the podcast. that was a few years ago, and when she described Codevarium, she talked about building tools for microbes that are difficult, sometimes impossible, to study in the lab.

Erum why is that? And why has biotech historically focused on such a tiny fraction of life, and where is the science going today?

Henry It's just really hard. There's too many parameters. You bring in an organism, you don't know exactly what to do. Typically, what we do is we throw it in some, really rich growth media, right?

Henry So it's like, it's almost like a buffet. And you're thinking, "Well, everybody loves to eat this. How about this organism? We just throw it in and it can eat this." And some do and some don't, because some depend on all sorts of different nutrients, different physical conditions. And that's just really reflective of how many niches there are in the environment, how many [00:22:00] other organisms a microbe lives with, interacts with, what is the space that they occupy within the neighborhood of microbes.

Henry So classically, we've had really great microbiology that was simply coming out of things like livestock, farming livestock, and, that's just was part of what drove human society. But we haven't really been able to study many of the other ones, even in livestock. So this idea of the gut microbiota that people are thinking about for humans, well, animal scientists have been trying to study that for a very long time.

Henry They know all sorts of wacky and wild things about, animals and their gut microbiota. I'm gonna just take a second to talk about non-model way to look at non-model microbes, uh- ... I had the pleasure of visiting Purdue University, a few years ago, and I visited their, livestock or dairy farm research [00:23:00] area, and they showed me a fistulated cow.

Henry Very simply, what is a fistulated cow? I'm not a, was gonna say a cow biologist. We'll just leave it at that. I'm not a cow biologist, but they have multiple stomachs, and one of them is really close to the surface of the skin. And so what people have done is they've actually been able to do a bit of surgery and put a cork against the cow's, one of its stomachs.

Henry And so you can pop that cork off, and someone can reach in with their glove and scoop out a bunch of gut bacteria that lives inside that particular chamber of a cow's stomach. So that's one way that you can study it. And so why is that relevant? Well, that's sort of outrageous, but that also reflects how difficult it is to replicate those types of conditions in a lab, right?

Henry the fact that we had to do this surgery to do this to a cow so that we could sample something within its native environment means that something [00:24:00] is really complex. it's about the, the heat, the humidity, the, I don't know, the gastric juices. So there's all these things that I'm not sure I could really comment on and, it would be fun to have someone within the animal microbiota sciences come and comment on.

Henry Butthat's a example of how difficult it is to study all of these other microbes out there.

Erum first of all, yes, we'll have to bring Kevin Rohlfs on the podcast because he is an expert in cow microbi-microbiomes.

Erum we got to see him at Synbiota this year.

Erum but great content for TikTok, this whole idea of like cow stomachs because,were mentioning that, Joshua Lactor of Roebling had talked about mulcher stomachs, and it got like 50,000, 60,000 views on

Speaker 8 TikTok and all the comments I'm trying here Yeah So- I'm trying here, yeah Okay. All right. Kyle's trying Let's, we, okay, we got one. So I'm- Let's see, let's see what riffs. Let's see what riffs I'm gonna, continue that conversation by saying

Karl Cornell also has a [00:25:00] fistulated cow, and whenever my son Tomas would feel depressed or, uncertain about what he was doing, I would say, "Have you gone to see the cow yet?"

Karl And he'd be like, "Why would I do that? It's so gross." But anyway, I think it's a great example, Henry, and what it reminds me of is in our conversations, one of the things you mentioned is you guys had to come up with a way of, growing, microorganisms under high pressure because there are a lot of o-organisms that live like at the bottom of the ocean under conditions that humans would just not be able to tolerate.

Karl So can you help our listeners visualize what they would see if they came to Cultivarium's lab there in Watertown, Massachusetts? If they interacted with your platform, what would they see was happening?

Henry What we have a lot is you come in, there are little chambers, call them incubators, of all different temperatures that either are static, they don't move, or there's a little stage in there that moves, and that is to shake them.

Henry We also have ones that are [00:26:00] sealed against oxygen because there are microbes, like from the gut or from the soil, that are anaerobes, so they do not use oxygen. In fact, if you expose them to oxygen, they die. they accrue too much oxidative damage, for example. So they really literally just cannot survive.

Henry Now, one of the initial ambitions was, let's culture a bunch of things. Let's get a hydrothermal vent just replicated using hardcore engineering. That is just really, really hard. So what we did in our first two years here was we were studying how other people study growing microbes. So there are some immensely impressive campaigns.

Henry there's a Japanese scientific group that has spent, I think, seven years trying to culture one particular microbe, in Archaea. and they have finally been able [00:27:00] to say, "We think we got it." but it took them about seven years. And that's an amazing feat of patience, diligence, persistence, all of those, all of those things, which honestly, I don't know that that's the type of science that we do here in America.

Henry and I think that's okay. That's okay. I think in science, we need a portfolio of people attacking things in different ways. So one of the things that we ended up doing was we said, "Okay, When it comes to growth, just growing a bunch of cells, what are some of the things that people miss? What are some of the things that we really would like to say about how you grow cells?"

Henry So what we did was we took a look at all of the different microbes, bacteria mostly, that have been taken from the environment. Someone has st-stashed them in what's known as a strain bank. So, can think about it literally as a bank where researchers say, "This is awesome. [00:28:00] I have this thing. I grew it in exactly this way.

Henry You gotta keep it forever for everyone else to study." And so we use those because people have already put in a tremendous amount of work, hundreds of years' worth of strain banks. we want to leverage that and try to push that work on. What we found are a couple of interesting things.

Henry Number one, if you take a look at all the different recipes for how you make the culturing media, we call it, or the broth that, these microbes have to live in and they eat and they grow, it's really funny because scientists love to name things after certain people or themselves. So there's a whole plethora of recipes where it's just pretty much the same thing, but it's named slightly different.

Henry Just like, you know, Grandma Lee's, awesome pork chops versus, Carl's grandma's awesome pork chops. That type of thing, where there's a few tweaks here and there, but at least from a scientific perspective, and we're not molecular gastronomists, we're just simply saying, "What is [00:29:00] a reproducible way to grow these things?"

Henry There's just not that many-- We don't know exactly what is the simplest uniform way to grow something. So what I'm basically saying is it's, really empirical. There's a lot of experimentation. We don't have really the time to say, "This is exactly the recipe for every single type of this particular bacteria."

Henry And so there's just a lot of From a pure science perspective, there's a lot of variance or maybe there's a lot of noise. So we're trying to focus on how can we standardize as much as possible so that scientists speak the same language. so going back to your question originally, which is how would people interface with, our lab?

Henry What would they see? We're really trying to say, what is the simplest, most basic thing you can do so that you can grow a bunch of this stuff, this particular bacteria, and then you can study it. You can study its genetics. You can figure out, for example, with Radiodurans, you can try to figure out by turning genes on and off, [00:30:00] how does it do all of this DNA repair?

Henry How does it resist all of this radiation? so there's lots for other scientists to work on. We don't claim to do it all. We're trying to get people tools and get people the ability to play.

Karl find it so interesting. So I studied plant cell and tissue organism culture with, a guy named Murashige, and he has Murashige salts are named after him.

Karl but there's many recipes of Murashige salts depending on what you're trying to do. And so I find this conversation to be incredibly satisfying and also befuddling because we know there's so many kinds of microorganisms out there, and they're all gonna feed on different things. But would you say, Henry, as a follow-up question that, you think that there could be basic recipes, so you could say, "Okay, these guys are gonna feed on this."

Karl And is that the number one question you need to answer? Like, you have to be able to cultivate them in order to study them.

Henry that's a great question. We take it pretty simply, which is we need to allow enough of these to [00:31:00] grow in a reproducible way day after day so that we can study them, period.

Henry Now, are we optimizing them for X or for Y for this particular thing that's gonna happen or that? No, we're not, right? So, maybe as a very loose, metaphor If you're running a zoo and you just wanna have animals there that you can then study, let's say behaviorally in a very humane, very positive way, what you wanna do is you wanna give them what you think is generally nutritious.

Henry You know, I'm not trying to optimize for the cheetah to run at top speed. I'm trying to optimize for what does it generally wanna do? Like general behavior type of thing. So that's the same approach that we're taking here, which is there is a lot to study. You can go into the genome, you can take a look at different pathways.

Henry You can say, "Wow, if it eats this thing, it activates this other thing." There's all these really interesting properties that others can come and follow up and study. But the key thing is oftentimes we're [00:32:00] working from a point where you can kind of grow it, you can't make too much of it.

Henry Sometimes it doesn't grow day to day. So we try to do that science where how do we put it in the right condition, whether that is do we need more-- add more salt? Do we need to change the pH so that it's not so acidic or that it's more basic? How do you get it to be reproducibly grown to a certain amount that we can then work with it in all the other aspects that we want to, when we do that study of its genes?

Erum Yeah. That's incredible. and also to follow up, these recipes are all online on your platform, right? You're not, selling any microbes. No one can actually physically interact with these microbes. So just there's a whole platform that you have that's a digital platform.

Henry yes, yes. We have a digital platform, and a lot of what we're trying to do is we're trying to be another knowledge layer on top, which is strain banks already exist.

Henry There's ATCC, there's DSM, there's many others that we can [00:33:00] name or we can drop somewhere if, if people really wanna get into it. And they already have all their own awesome data. What we're trying to say is, "Look, go to that primary source. That's where you get the strains." They will do all of the logistics and all of the drop shipping of that, whatever is needed.

Henry And what we're gonna do is say, "Look, if you get it, this is what we have found to be the best way of working with it." And yeah, we make this data available. you can come on portal.cultivarium.org and request an account and look at all of the data that we've synthesized and tied together so that it's unified across databases.

Henry You can pose questions if you want. You can try to get others to answer your questions about a particular organism that you're working on. So we're really trying to make sure that folks have a place to accelerate their research.

Erum okay. That's incredible. So you had mentioned that there's only a handful of, microorganisms that have been used for research. Can you tell us what becomes possible when we can engineer [00:34:00] entirely new branches of life, especially fungi and archaea? Yeah,

Henry I am probably not the first person you need to ask about it.

Henry There are many others within our industry who might talk about growing houses or using fungi to eat houses. maybe we can make awesome replacement leather. We can do all sorts of fantastical things when we try to leverage what nature has already evolved to our needs. What is particularly interesting to me is around two aspects.

Henry One is, a lot of these fantastical properties, and again, just for sake of argument, this ability to repair DNA, and there's also the ability to, sporulate, which means you go into a state where you are extremely hardy to external conditions, and then when things are good, you come back out, right? Now, if you come on this very loose mental journey with me, what are-- how can we use those types of things?

Henry Well, this idea of sporulation or of preserving [00:35:00] yourself, almost like a bio stasis, can we use some of these ideas similarly in organ preservation, in, tissue regeneration? There's a lot of parallels where, as it stands, we've used a lot of these model organisms to study fundamental biology, DNA replication, DNA repair, how proteins get translated.

Henry So there's a lot of, more exotic capabilities that we can study using simpler models like bacteria.

Karl You know, we were talking about, fungi and archaea, and th-this all falls under the kind of general, header of unknown microorganisms. These feel very alien to most people.

Karl And what was the reason that you and Cultivium decided you wanted to go after those organisms? What was it that, you felt like current today biotech is missing that would be fulfilled by you guys getting more knowledgeable about this?

Henry There's a personal answer, and then there's a science/industrial answer.

Henry The personal answer is that when I [00:36:00] immigrated to the States, we lived outside, we lived in Arizona, which is really close to the Biosphere Project. And so if you don't remember, the Biosphere Project is this giant geodesic glass dome where the idea was, "Hey, how can we recreate an ecosystem? Let's just shove a bunch of stuff in there, see what works.

Henry Can humans survive in it?" With this idea of how can that be representative of our planet, and how can that be representative of us going off-planet? So that was a personal childhood reason of, I don't know what goes in there. What is the laundry list of things that is required for a human or a society to live?

Henry And that generally makes you very curious about all sorts of different things, whether that's plants, animals, microbes, all of these things. So that's the personal side. The science and the technology side really is that a lot of us got into science to be able to explore a frontier, to be able to say, "Hey, what is this new phenomenon?"

Henry And maybe that is a way that we can bring [00:37:00] something that is awesome that will make a step change into how we think about things today. So there are awesome people out there pushing the boundaries of what's possible in science and industry, and that's great. But one thing that we have seen over time, even through a signal like Nobel Prizes, is that there are, are several Nobel Prizes awarded to things that you find in non-model organisms that then are transformative to everything that we already know we care about today.

Henry That are things like the green fluorescent protein from jellyfish that has helped us look at how cells behave and how genes behave, right? Who would have thought to look at jellyfish? That's amazing. That is, again, the CRISPR-Cas9 system that came from all sorts of different bacteria, including yogurt bacteria.

Henry So there are these ideas where you want to say, "Wow, what has nature invented? And how can we just go out and [00:38:00] find it and then try to see how we can use it?" Right? So I'll summarize this by saying there's really two opposing forces here. The personal side is, if we ever find aliens, I want the officials to come and find me so that I can go study it and tell them what it's about and how it works.

Henry That's, that's the summary of that part. and then the science and engineering part is just, how can we leverage the fact that nature has invented a bunch of stuff, and how can we basically just be kind of lazy in not having to invent everything from scratch and saying, "That was cool.

Henry Let's take that, tinker with it, and then repurpose it," right? So We believe that there's a lot of opportunity to make an impact on the science in terms of fundamental understanding about biological systems and to be able to unearth tools or genetic programs that then can be meaningful advancements to health, materials, planetary scale issues.

Erum that's incredible. I will have to say that, being called upon when [00:39:00] aliens are discovered was my main motivator to study, forensic chemistry with my undergraduate. So we have same motivations.

Henry It'll-- It's gonna take a team. It's gonna take a team. Yeah. I hope, you know, we wanna all be called up.

Erum Henry, you're talking about non-model organisms, and you're sharing with us that this means dealing with uncertainty, failed experiments, and systems that don't behave predictably. So can you share a spectacular failure that ultimately led to an important insight?

Henry I'll give you a very specific example, and we've, shared a, manuscript that's out on bioRxiv.

Henry So this is a server where you can just see science, being published as soon as possible. So here's one thing that we've learned. There's one particular bacteria called Sporosarcina pasteurii, and it is used to basically make biocement. this microbe loves to make these really, mineralized material if you [00:40:00] give it the right, s-input feedstock.

Henry Now, there are companies that have been launched to try to commercialize it at scale, and there's just a lot of interest in trying to make cement more green. Now, one of the key challenges of people trying to commercialize this, and maybe even a bigger challenge of people trying to understand how this works and trying to turbocharge this organism's ability to do so, is that no one has really been able to turn its genes on and off.

Henry We haven't been able to do DNA delivery, which is what we call it, to be able to say, "Here's a piece of DNA that we've, designed, and it specifically either turns something on, turns something off, interacts with this." And so you need to deliver that across the cell membrane into the cell.

Henry And then you need to be able to make sure that that piece of DNA functions. So this is the core of what Cultivarium is built to do, is built to say, "How can we actually do these manipulations on the genome level to these organisms?" So [00:41:00] long story short, we tried to tackle Sporosarcina pasteurii directly head-on.

Henry We failed spectacularly. All of our tools, all of the things that we tried just could not get it to happen. So what do we do? We gave up like most people do. And then what we said is, "Okay, well, we have this other idea, which is, you know what? Let's just go out there in the wild, let's collect a bunch of samples, and let's pick a bunch of these colonies of different bacteria and, and let's see what we find.

Henry so then what we did was we went out into the wild, we got a bunch of samples, we put them on a plate, things grew, we picked all different ones, and we decided, let's try to figure out how many of these we can deliver DNA into that we can, turn genes on and off.

Henry And it turns out that we got many of these to work, and upon further analysis, what happened is that we actually ended up finding a bacteria that was a cousin of sporosarcina pasteurii that we were able to do this work with, [00:42:00] this genetics work with. And we thought, "Okay, that's really, that's really cool.

Henry What if we took the things that work here and directly applied it back to sporosarcina pasteurii?" And in fact, that was the breakthrough. We previously had tried all of these things and, this was part of our, part of our standard workflow. We thought this was the general way to approach all of these problems.

Henry And how we ended up being able to figure this out was we went out into the wild, we studied a bunch of other things, and we thought, "Oh, wow, this was related to this, and somehow the methods match," right? And so I think the, point of telling that story really is that oftentimes in science, we have this one goal, and we're very immovable about the way that we approach it.

Henry We think there's a linear pattern to it, and that's, uh, this is a story as old as scientific time, if you talk to a bunch of people who do science. And there's always room for play. There's always room to [00:43:00] stumble and wander and to be able to look at a bunch of non-model organisms that are even more non-model than the one that you were hoping to work on, and then you can bring those learnings back and apply.

Henry So that's really one of the key lessons that really reinforced both our, our way of doing science, which is let's be ambitious, let's have a target in mind, but let's, be open to changing the way that we approach it. Let's have some patience and some grace on when and how we get there. And that also further highlights, wow, there's incredible value in just studying what's out there.

Henry Let's not ignore what's out there just for the sake of what we think we want to achieve today.

Karl That's beautiful. Yeah, I love that, What happens when you're able to unlock organisms that have evolved for extreme environments like heat, salinity, acidity, radiation? What kind of real-world applications are you most excited about?

Henry Here's one that's top of mind for us these days, which is oftentimes when you're [00:44:00] talking about fermentation, right, fermentation, giant tanks, lots of material use.

Henry It turns out when you start thinking about it very deeply, and especially when you are not only the process engineer but the people who are trying to make money off of such intensive processes, you start caring about things like how much heat are you putting into the system? How much are you cooling the system?

Henry And, how much sugar are you feeding in? What kind of sugar? And then here's another one that's, fun and important is how much fresh water are you using, right? And so we know that fresh water is, there's fortunately enough for most people in the world, but that is-- it's never a good thing to compete, to have processes compete with fresh water because humans need fresh water.

Henry And if we can wean other things in the world, like fermentation organisms off of fresh water, that's, good. We can use it for other aspects of human society. So one of the things top of our mind is how can we [00:45:00] reduce fresh water burden and not have our fermentation products that might be fermenting things that are commodity chemicals.

Henry Let's not have that compete with fresh water. So what does that mean directly? You might wanna use organisms from the ocean, right? There's lots of ocean water. Can we pump some of that in? Can we use an, engineer, an organism that thrives in seawater, or at least in that salinity, and have that be our source of water that we continually use?

Henry So that's one example. Along those same ranges for the very practical outcome is there are certain organisms that grow really well in human waste water systems, right? Let's use those so that we can take wastewater and both get cleaner water out on one end and get high-value products out on the same end, right?

Henry Or maybe split into different streams, but you get what I mean. So those are some of the very practical aspects where using [00:46:00] more extreme biology or what we consider not your classic model biology that we've been able to commercialize, that might help us do all sorts of different chemistries and sorts of different processes that are not only better for a lot of the intensive processes that are now competing for our natural resources, but that might actually also be commercially more palatable.

Erum N- you have me thinking about, like, underwater bioreactors. So like my mind's like spinning now. This is why I love talking to you. you have trained with pioneers like Jim Collins and George Church, both known for engineering biology at scale. How do those experiences shape your philosophy around building tools for the field rather than just products for a company?

Henry Those are two, two very, very ambitious and very complex professors, and leaders of the field. So, so really the great thing about Jim is that he's very incisive about what he cares about, about [00:47:00] what he thinks that scientists should care about, what is the actual problem, how do you actually tackle that problem.

Henry And then with George, I mean, what can you say about George other than the entire universe of possibilities is his immediate playground. So being able to go there and train with him, and more importantly, be part of the wonderful ecosystem of graduate students, postdocs, philosophers, artists, and all these other folks that pass through the lab, that's, that was really a boon to be able to not only think about science of all different directions, all different types, all different possibilities, all different timescales, but also the what does it mean to have art reflected in the science we do?

Henry What does it mean when we push science to the extreme and it maybe is viewed in an evil way, or maybe it's not so palatable to other people. So we start thinking about not only ideas of biosecurity, ideas about, what are the ethical bounds, but also what does it mean for us to invest in [00:48:00] different places in science, and how do we reverse some of the technologies that we've been building so that we can make it not a unidirectional choice, of what we're doing.

Henry So it, it was a real pleasure to be able to train with both of them, and of course, both have really influenced the way that I think about science here at Cultivarian, which is we're going straight to the point. What is the problem? Let's try to think about it using all different approaches. Let's try to think about it using all different disciplines.

Henry And the universe of possibilities, we want that at our fingertips. So we try to emulate in our own little way here the ethos of both labs.

Karl I wonder if this is a good time for us to maybe diverge from the questions and talk a little bit about the state of science today. we started the conversation and you, and you said, "Yeah, maybe I can talk a little bit about, my point of view on what that is." we seem to be in this very interesting place where, science funding writ large seems to be decreasing.

Karl A number of researchers have left the United States. We're in this [00:49:00] kind of like ideological war against China, where they're spending a lot of money on research. where's the silver lining for American science?

Erum I also want to add to this question because AI.

Erum Yeah. you're collecting so much data, so much information. There's so many microbes out in the world. How does that also play into this? So where's science going?

Henry if I knew exactly where science was going, then I probably should run for office. but thank goodness I'm not. I can provide some observations and some hopes maybe.

Henry The way that science is being funded or manipulated performed here in the States? I think that there's a lot of anxiety around that, of course, in the US, and there are certain labs that are getting hit harder than others There's not a lot that we as individual scientists can do about that.

Henry And so I've tried to take a different approach, which is what can I learn about what the system has resulted in? What can we learn about how we do [00:50:00] science moving forward? So there's a couple things that I, I would like to share as hopeful things, which is number one We as scientists should and think about how we deliver more positivity and more goods to society.

Henry that is warranted. A lot of us got into science, yes, because of the joy and the wonder of exploring, but fundamentally, we are all trying to make a really deeply meaningful impact on society, just maybe with slightly different time scales. And we need to figure out how to approach that with a portfolio.

Henry Just like your 401K, my 401K, everybody's investment fund, everything is a portfolio of what's gonna pay off in the near term versus what's gonna pay off further down the line. So can we build better systems to balance that risk? We should, and we will have to just because of the way that the science infrastructure is now being changed.

Henry So I'm here for it. And so I think that that's one thing that we can look to in the future, which [00:51:00] is how do we build a better system so that science can serve more, and science can be a clearer positive force for more people. I think that what we're hearing today are a lot of concerns, mistrust of science.

Henry what is the value of it? Well, let's, now do a better job of making sure people are educated on how well science can inform us of exactness and of just this is the answer no matter what. I think the core of science, as many learn in elementary, I think, is the scientific method, is a continual iterative loop of, "I'm not sure.

Henry I'm trying to figure it out." And somehow we've lost sight of that in the public, which is, we don't know, everyone. Here's the best evidence that we have, and we're all trying to figure out the truth so that it works out well for us. But it's good to ask questions. It's good to challenge it. It might need to be put in a certain way that is, much more productive [00:52:00] over a period of time.

Henry But what we're seeing is just giant backlash against the work that we should be doing, which is communicating more, making sure that the public is with us more. So that's one piece. in terms of AI I think it has the potential, and I believe it is an incredible force for positive outcomes, period.

Henry The way that I think about it is, it is, not only coming in the way that almost all nations on Earth seem to be investing massive amounts of money in it. It, that it's basically inevitable. It is here. It is coming. It's gonna be more. More money, more intensive, more attention paid to it. The best thing we can do is make sure that it is used in a positive way for science and for other aspects, of society.

Henry So the way I think about it is let's grab onto the horns and hold on for dear life and try to steer it in, in a particular way. And we've found incredible uses for, for some of these AI systems ourselves. It's an [00:53:00] ongoing thing, but, that's work to be done

Karl Amazing. So, you know, we're getting close to the end of the interview, Henry.

Karl One thing I did want to bring up is you guys at Cultivarom originally started off as a focused research organization. Now you guys are calling yourself a frontier research contractor. Can you explain what the structure is, and why do you think the future of biotech innovation may depend much more on shared infrastructure?

Henry We started off as a focused research organization with the idea that there are certain problems in biology and in science in general, where much of it remains unaddressed or not addressable because we don't have the breadth of expertise or the industrial-scale resources to bring to this question.

Henry Cultivarom was established so that we can bring this intensive resource and the broad range of experts to be able to say, "What are all the ways in which we can grow organisms, study their genetics, and then to be able to [00:54:00] build tools so that others can develop applications, both for fundamental science research and for translation purposes."

Henry So we've now also adopted this new mantle of a frontier research contractor. And for more of this, you can read about this term FRCs, or you can read about BBNs in general, which is what this type of model is based off of. But the general idea is we're trying to experiment with organizations, not only with organisms.

Henry The organizational experiment that we're doing is to say, "Look, we think there's a lot of opportunity. We want to continue down that North Star of mission and intent. But along the way, we understand that we need to generate some amount of capital to continue to fund this type of long-range research, and that some of the things we build could probably help certain folks today."

Henry Right? So it's, again, the, portfolio [00:55:00] of what are some of the technologies we built, how can we deploy that today so that others can benefit from it, and then we can also benefit from flowing capital back in, and then how do we continue this journey to this long-range goal of unlocking as many organisms as possible in our biosphere.

Henry So that's what we're working to accomplish, and this is the time to do it because everything is uncertain, you might as well play and try to navigate. And so I think that we're trying to take the charge and to say, "Hey, maybe this is possible. We're gonna give it a whirl. Check back in, and we'll give you an update."

Erum Yeah. I mean, I definitely want to learn more about that. I think that warrants another episode maybe with some other people and you that are, looking at FROs and funding FROs, because I think in the world of biotech companies, there needs to be more, different organizations, as you're saying, or funding models or business models.

Erum Yes. That'd be great ... you know, we talk, Kara and I talk about that a lot, is just [00:56:00] a lot of people are just venture capital. that's all they see as a- The only solution. The only solution, the only way that they're going to raise capital. But that's not the only way. There's other ways of funding.

Erum There's other ways of setting up a company or an organization and, being able to lay it all out for innovators so they can see which would work for them, that there are other ways of creating organizations. so we'll have to circle back on that, 'cause we're nearing- Sounds great ... the end here and there's so much more to talk about.

Erum Yay. Okay. So we have just interviewed Senator Todd Young. That will be the episode before this one. Senator Todd Young is the chair of the National Security Commission of Emerging Biotechnology, as you know, and they proposed legislation to create the America's Living Library Act, which we've talked about at length.

Erum the idea that we can, sample the US public lands for different organisms, and sounds like there's, like, a great compatibility with Cultivarium. I'm curious if you engaged with them at all and how could Cultivarium [00:57:00] support such an initiative?

Henry I think it's a phenomenal thing that's been proposed.

Henry I think Senator Todd Young has been at the forefront of helping push a lot of not just sensible but really exciting initiatives, I, I really commend him on that leadership, and I hope that a lot of that works out. Cultivian would be delighted to support, and we've sent notes into, his team to, to say exactly that.

Henry We would be delighted to support in whatever way there is value. The Living Libraries Act is a great way to start. The US is an entire continent east to west, right? And we have all the different bio-biomes. So certainly we must have incredible, incredible inventions from evolution that we can take and bank from nature and to be able to use that for positive outcomes.

Henry Absolutely I think we're certainly not the first to think about it, and we might actually wanna hurry up a bit. when you take a look at what has been the equivalent elsewhere in the world, [00:58:00] Europe, the Netherlands, for example, the Dutch have been doing a lot of this.

Henry other countries where they care a lot about resource efficiency because they might have con-concerns about their access to resources. They've already started investing in natural abundance, all the natural resources that they can tap from their, country. And so I think this is a-about time, and I'm certainly grateful that someone like Senator Todd Young is taking I, I want to say that I would love for it to go even further, which is it's one thing to take a sample and to do the DNA sequencing and to say, "Here's a list of stuff," right? It's another thing to say, "Well, then that particular organism we can then take into a bioreactor and then ferment it and then get a product out."

Henry And the hardest work of what is being proposed is there has to be teams that go out there and collect this material. And so if you're gonna collect this material, but then basically, lyse all the cells, you know, just basically kill all of [00:59:00] them and take their DNA so that you can sequence them, well, that's all good and fine, but I would encourage us to think about, can we just take a sample and bank it, right?

Henry Almost like the Svalbard Se-Seed Bank, which is, let's have a copy, and let's have multiple copies, right? I think one of the key things, that is a shame, for example, about the, you know, there's this tale of the Alexandria Library and how it got burnt down and how that set science back hundreds of years.

Henry Well, the takeaway there isn't that it burnt down, it's that there was only one copy. That's the actual shame. If we made multiple copies, and if we were able to treat it as a resource, then it would be distributed, there would be no harm in, having it everywhere.

Henry So th-there's a lot to be said about that, but I guess, what I can say is overall, I'm really excited about that effort. I'm really excited that the US has started to think about that, and that we would be happy to contribute where it makes sense.

Karl Awesome. So let's just put on our future hat. thinking 10 years in the [01:00:00] future, what scientific breakthrough or enabling tool do you think will completely transform our ability to study and engineer the microbial world?

Henry Well, if we're putting on our, our future hat, then everything is possible.

Henry And it's not just microbes, it's all organisms on Earth. And what is possible is our ability to say, "I'm interested in this particular property that I've observed in the wild. I want to know exactly what the genetic blueprint is, and I want to understand how I protect that in an ecosystem or ecological level, or how I imbue people who are in need, either because of disease or because of, I don't know, maybe some vanity."

Henry how do we give them that possibility, right? so I think really anything's on the table. there are ways in which we can think about the base case level, which is, yes, let's eradicate disease, just like what many other folks are working to do. But there's another [01:01:00] level which others in the industry are really trying to promote, which is, how do we live our best lives while being beautiful, while eating whatever we want or having whatever vices we want, and how do we enable that through better peptides, for example?

Henry So there's all sorts of ways we can think about the future. I would say that the key thing here is we need to engage with the public, we need to engage with regulatory bodies. I know it's kind of a downer, but the future for bio has always been whatever is possible that we see in the natural world, but it has always been gated, for good reason, by what do we accept, in society.

Henry And so that also would benefit us modernizing that, having conversations around that. And I think that, podcasts like Grow Everything tries to highlight that. I think that's great. I think that other e- efforts out there trying to propose new bills, trying to bring more biology into everybody's everyday lives, I think that's also great.

Erum Oh, thank [01:02:00] you so much for the plug. Awesome. We didn't pay him for that, folks.

Erum You're not done yet. We have our quick-fire questions. Are you ready?

Henry Let's go. Go, go, go.

Erum Okay. All right, here we go. If you had to pick one forever, fungi or archaea, what, which one would you pick?

Erum Why?

Henry Archaea. They are really weird. They are bacteria in many ways, but have systems that look like eukaryotes or like humans. it really feels like a crazy mixture of both. Lots to study there

Karl Okay, what's one biotech buzzword you wish secretly would disappear?

Henry I have two. I, would call it tech bio and the virtual cell. I think, I think both are outrageously overused. tech bio, biotech, it doesn't really matter.

Henry We're just trying to make biology work however it needs to work. Yeah. I will use any tool at my disposal. Let's make drugs. Let's make, better tools for society. Let's just do it, andthe [01:03:00] domain is biology. Let's call it biotech, or if people really want, let's call it tech biotech. We'll have tech everywhere.

Henry That's one piece. Virtual cells, we've been working on virtual cells for a long time. I know it's come back. we would love to compute biology. certain people are computing aspects of biology better than others. But honestly, developmentally, here's what I think about where we are in terms of computing biology.

Henry We are still children playing with shapes. All of protein engineering- ... is playing with shapes. Let's learn how to form full sentences. Let's learn how to communicate our intention. It's all great. Let's keep it going, but, yeah, fewer buzzwords. Let's just keep the progress going.

Erum Yeah. Great. Okay, so if you could engineer any organism tomorrow, what would it be?

Henry right now I'm super fascinated with the apple snail. this is a system where the apple snail has a complex camera lens eye, [01:04:00] like the human, and, a little bit grotesque. What you can do is you can cut the eye off, and the apple snail will regrow the eye in its entirety. so that is crazy. That is a complex structure.

Henry There are some really, intense neuronal connections there. How does it do that? I wanna know.

Erum Oh, we should talk to Mike Levin about that. He'd be all over it.

Karl There you go.

Karl Okay, last one, last one. What's one scientific mystery you hope gets solved in your lifetime?

Henry Are we alone? Is it a simple organism?

Henry is it a complex organism? What kind of language do they have? what kind of substrate do they run on? Is it nucleic acid? Is it something else? can they travel faster than light? How can we travel faster than light? The universe is really big. I think I've listed at least one big scientific question out of that.

Karl There you go.

Henry I still believe. [01:05:00]

Karl Yeah. I do believe as well. Henry Lee, this has been a joy. It's always fun to talk to you. We're so glad that our audience gets to listen to your wisdom, and, thank you for coming on the Grow Everything podcast.

Henry Thanks very much for the invitation, Carl and Aram. It's great to see you again, and I'm sure I'll see you around pretty soon

Karl Iram, what did you think about that episode with Henry? Henry's so great, right?

Erum Oh my [01:06:00] gosh, he's so much fun to talk to. I think we could've talked forever, but we don't have that much time, so

Karl Yeah

Erum But of course,

Erum And I just love how Henry framed non-model organisms as this massive untapped frontier versus the few model organisms that science relies on today. and Senator Todd Young in our previous episode, if you have not listened to that episode, I highly recommend that, he also talked about that, that there's so much information and intelligence and functionality that is in the world of biology, and it's just sitting right there in front of us, and all we need to do is look.

Erum Looking is hard, because you need a lot of equipment and being able to understand how the genomics works, how the phenotypes express themselves, all of those things. but I'm excited that Henry has this amazing organization that's being able to make it more easy to work with non-model organisms. What did you think, Carl?

Karl what I love about Henry and the fact that we know each other and able to text [01:07:00] him and get to have these regular conversations with him, is just the way he thinks.

Karl And he has said this to us, and I know we've mentioned on the podcast, if you're trying to do something with biology, there's probably a microbe out there that already does it, and it's just unfortunately we don't have enough knowledge of the microbiology on our planet. So we're stuck, or scientists are stuck with these four to five model organisms that they use all the time.

Karl So I'm applaud, Cultivarium's efforts, and I want to see much more of this.

Erum Yeah. it is very hard, just a very ambitious project to be able to culture all these microbes. If it was easy, it would've been done before. but to be able to, find these patterns, create the infrastructure required to, not only study but, gather all the information, put them on a database, make it more accessible, working with all the different biobanks that have these different microbes and other organisms that are available to use, but they're just [01:08:00] available.

Erum They don't have all the information that Cultivarium is generating through their, high throughput studies and, through their, different protocols that they have. It's, or we both had a chance to go see, Henry Neely at their lab, and it is quite the operation to see all of their different, lab benches and equipment that they have.

Erum but they're bringing,a lot of, discipline to this exercise of being able to, cultivate all these different microbes and making it easy for us. And then I just think, we mentioned this in the episode, but, you know- with the American Living Libraries Act and this, the ambition that's behind it to be able to, sequence the, organisms that are in America's public lands and create this database that is, revved up with AI so you'd be able to really, look at this data and being able to use it.

Erum it's great ambition, but who's gonna do the work, right? and here's Cultivarium that has tools. They have the [01:09:00] platform, they have the intelligence, they have the people, they have a lot of things. I hope that this, they come together when this, bill becomes a law, and that, we can do this quickly because there are other efforts of, swabbing, urban landscapes and collecting those microbes to understand, what they do and, for example, our, friend Chris Mason, who is a scientist, that has studied astronauts, that has done, a lot of studies on subways and what microbes are living there and what's going on in the Gu- Gowanus Canal.

Erum He kind of spearheaded this whole, like, urban microbiome studies. And then there's this, network called MetaSub, which has scientists in different cities that are swabbing their urban landscapes, and then they are meant to process , those samples and put them on a database.

Erum But there is a huge backlog 'cause swabbing is easy. But then doing the actual analysis and getting that data up takes [01:10:00] a long time with today's, tools that some of these teams are using. But as Cultivarium is trying to accelerate this and making it easier to not only sequence these genomes but then to do something with it.

Erum You can't just sequence it. What else? So that's the easy part. H- how do you find which proteins can be made, and what's the next level? What can we do with it? Can we, find something that's, eating plastics? I mean, I know that's out there, but I'm just trying to paint this picture of what's the application here.

Erum How do you find the applications?

Karl thinking of the applications is that whole idea of, beginning with the end in mind, that Henry even talked about it. Like, the practical applications of this work are, greener fermentation, cleaner water, seawater-based bioprocessing, new biological tools, being able to really do biotech out in the wild, the so-called dirty biology that we talk about.

Karl And to me, that's super exciting. Again, like I said earlier and that Henry said, if you're [01:11:00] trying to do something with biology, there's probably a microbe or an organism that is already doing it. The problem is we don't have a broad enough picture of that, and hopefully the work that Henry's doing, living libraries, are all gonna make it more apparent, and that will mean that we've got this bigger tool chest to work with.

Karl And if there is something you're trying to accomplish, either you can use a wild-type organism that we know how to culture, or you can take information from one of those organisms and put it into another one to create the end product you're trying to do. So, this is all very exciting.

Erum Yeah. Yeah. And then finally, I mean, I just love how Henry wrapped it all up t-terms of what does this mean for the future, especially for science infrastructure.

Erum And, the fact that, Henry's organization was this focused research organization,

Erum And now that it's fun-frontier research contractor, that there are these different funding models and organization models that can be considered when you're embarking on such a huge endeavor like Cultivarium is doing, and that there needs [01:12:00] to be better public engagement when it comes to science and, and that for sure we all feel that, right?

Erum Like, this is one of the reasons why we have this podcast, is that we need more people to understand what is possible and what's the safe way, the right way of doing things versus the wrong way. what are the resources that are available. So that's really important. And of course, we gotta sprinkle AI on top of that and what can be done when you have AI to accelerate discovery.

Erum So very, very great conversation. Henry, we love you. Neili, we love you. Such a great organization. we're gonna definitely stay on top of them, when they have new discoveries, love to share those, and can't wait to have them back on. Maybe together, now that we do have an episode coming up with two people on, so maybe, at the end of this year, we can have both Henry and Neili.

Erum Fun dynamic to, to be on the pod.

Karl I think that sounds great. So as we close things out, just a couple of quick reminders. we are gonna be doing a live fundraiser at Genspace in Brooklyn on June 18th. The details are going [01:13:00] to follow, so stay tuned for that. And as we've mentioned in the past, we will be at World Biomarkets.

Karl World Biomarkets has an event in The Hague in the Netherlands coming up in June. So as you listen to this, the event is gonna happen very soon. And then in September, they'll be in Omaha, and Iram and I will be there as well. Use promo code GrowEverything and you get a 25% discount to attend.

Erum And thank you so much for tuning into the Grow Everything podcast.

Erum If you have any questions, comments, if you have any tea, biotech tea in particular ... please share it with us. I mean, we are so interested. And you know what? You can leave us a voice message. We could throw it on the air. Let's get creative, This is a summer of being creative for us. hot girl summer was a couple summers ago.

Erum Hot biotech summer, maybe we can do that. but our contact information is in the show notes, so please reach out. And don't forget to subscribe to our Substack so you can get Grow Everything delivered to your inbox every week. Let's grow.

Karl All right. Let's grow..