115. Gene-ius at Work: George Church on Climate Hacks & CRISPR Stacks – A Homeworld Collective Interview

[00:00:00] it's scaling down in size, up in complexity. And I think that's something that biology does incredibly well. And we're doing both.

[00:00:08] We're scaling up in to ecosystem size and nanometer scale precision

[00:00:17] Karl: Hey Ram, how's it going?

[00:00:18] Erum: It's going, Carl. very, very busy week. exciting times that grow everything podcast. We're so excited about this episode today. But I'm messaging lab. We are busy. We have clients to meet and we got to fly out right after this. So we need to keep it a bit snappy.

[00:00:35] Erum: But how awesome. That our friends at the Homeworld Collective, Dan and Paul, have collaborated with us to bring this episode to our Grow Everything audience. we're excited to more about this episode. But.

[00:00:47] Erum: We'll be great to talk a little bit about homeworld.

[00:00:50] Karl: so for those of you who don't know Homeworld, Homeworld is a collective that's developing social, intellectual, and funding infrastructure for the young field of climate biotech, and their goal is to make climate biotech as productive as medical biotech and, machine learning.

[00:01:05] Karl: They're a community of scientists and engineers. And they work at the frontier at the leading edge of climate biotech. we're big fans of theirs because what they're doing is very close to what we're doing and grow everything though. They tend to be a little bit more technical, in what they do on their podcast.

[00:01:20] Erum: their podcast is called the climate biotech podcast So if you guys want to dig deeper into the science But they also of course bring it to the level of business and commercialization good podcast to check out, of course We'll have them in our show notes but you don't have to dig into it too far because today's episode is Episode of the climate biotech podcast and this episode it's featuring George Church.

[00:01:44] Erum: big, big, big leader in the biotech space, leading thinker and Carl, don't you know, George Church?

[00:01:51] Karl: Yeah, know George. I'm not sure if he knows me. I feel like everybody is one degree or two degrees of separation away from George Church. He's a well regarded, well known, geneticist, molecular engineer, chemist, serial entrepreneur. He works at the Wyss Institute. which is a collaboration between Harvard and MIT.

[00:02:09] Karl: He's also the co founder of more than 50 biotech companies. And he is one of the leading minds behind Colossal Biosciences, which we've talked about on this podcast. Colossal seeks to de extinct the willy mammoth. And if you ever see George give a presentation. because he's around giving these presentations a lot, you will be amazed by his disclosure slide because it shows all the companies that he's either advising or has founded and it's a very crowded, amazing Clyde to see.

[00:02:36] Erum: he's incredible. and I bet several of the companies that we've interviewed on this podcast, have George Church on the board. I'm thinking of cultivarium,

[00:02:44] Karl: I think Henry was in George's lab

[00:02:46] Erum: cool. this episode is really, really interesting. It's going to give you a smattering of concepts that really ground the work and the. Industry that we love to promote and talk about. It really grounds it in interesting science, interesting ways to talk about it.

[00:03:01] Erum: So if you're an entrepreneur listening to this episode, listen for the words that George uses, and then stay tuned for after this episode, because we're going to give a little shout out about what homeworld's doing some great opportunities for people that are working in the climate biotech space.

[00:03:17] Karl: so this episode called how microscopic innovations can scale global solutions with George Church. Let's let that episode play

[00:03:30] George Church, thank you so much for joining us in this conversation. Who are you? Where'd you grow up? Yeah, this is to humanize. So I shouldn't mention the Skynet stuff, but the.

[00:03:41] Mudflats of Florida is a short version of it. Almost all my existence until I was 13 was right literally on the water. And, and I loved low tide because I could go out and stomp around to find the kinoderms and things like that. Did you always know that you'd be building the future of biology as a professor at Harvard?

[00:04:01] Far from it. I didn't even have any science courses until seventh grade. And even that was pretty primitive in Florida. I, I think at one point I was planning on studying river dolphins in the Amazon, the pink river dolphins. I learned a lot about outboard motors because I figured I'd be fixing outboard motors on the Amazon.

[00:04:21] And I actually made it to Brazil when I was 12 or 13, but didn't actually materialize and it's, um, had to settle for what you just described instead. There is still time, George. Oh, yes. So there's lots of times since we're not going to die, the more limiting thing is whether the river dolphins are going to die.

[00:04:42] That's, that's more of a problem. So what was the transition point from George focused on the dolphins and Amazon to George's people might know you from your papers today. I was always unfocused. You could call it, or polymath is the more generous version. There was nothing, no science or math or, uh, knowledge that I wanted to abandon.

[00:05:05] So I just kept accumulating it and looking for a, a combination. And that happens, I guess, sophomore year of college, I found crystallography, which required 40 transforms of math and physics and chemistry and biology and a lot of computing. So one thing, George, you've seen so much. I think me asking the question of where we are now, I think also helps contextualize your personal journey, which is that my mental model is that we're in a downturn right now of synthetic biology, bioengineering outside of health.

[00:05:38] Really like whatever you want to call it. And I'm hoping in this conversation, we get to go into climate biotech, but climate biotech sits alongside and inside of biotech. So when I look at what's going on right now, we see a lot of the big companies that SPAC or went public in 2020, 2021 down 90%. A lot of startups are laying people off.

[00:05:58] In many ways, it seems like we're on the cusp of such exponential growth technically, but then we're also in this collapse of business models, just not working out. And so. Well, I do want to spend time focusing on long term goals, but you've seen a lot. You've been writing world changing papers since the eighties.

[00:06:14] So I'm just curious, like when you look at the site, where we are in the cycle now, does it feel different at all to you? Does it feel familiar? I'm curious how you look at where we are today. The first thing is to take Doug Adams advice. Don't panic. And the second is if the old aphorism, buy low, sell high.

[00:06:32] The key sometimes ignored part of that is you have to find the low point to buy in. So when you're at a low point, that's the ideal time to start building things. Maybe don't require that much money because it's everything is undervalued. And then it'll take off. Almost all these are financial cycles that are fast relative to a career timeline.

[00:06:53] And in the exponential isn't going away. These economic downturns generally have very little to do with science. They have to do with other. Political things and whatnot, the science is exponential is fairly gratifyingly constant. I mean, I think you've been one of the leading figures of showing that biology is outpaced Moore's law in terms of sequencing.

[00:07:16] And so I do like to focus on the exponential. So let's talk about these goals and where we're going. I think one way to eventually want to hear what's really interesting to you and one way to provoke that is to think about the ohms in biology, right? So we've got the genome, the transcriptome, the epigenome, the connectome from neuroscience.

[00:07:34] What are the future ohms that excite you, hopefully relevant to planetary scale biotech? For example, metabolome comes to my mind is still operating below several orders of magnitude where it could be, but what are the future ohms and what are the ohms that we still have a lot more exponential growth in?

[00:07:49] I think an interesting variation on the metabolome are things that you can observe from drones or from satellites. And there's a lot of synthetic biology that can help amplify that signal and turn it into something that's reflective of things you care about. So for example, when I was in Siberia, I was up close, personal to monitoring stations for carbon dioxide and methane, because for the first time in, in recorded history, when I was there, it was the first time that a permafrost melted and didn't fully refreeze.

[00:08:26] And there's a lot of methane being produced throughout the Arctic, not just Siberia, and it's the consequence of it being one of the richest storage, it both produces. Fixed carbon, and then it stores it in the ultimate form. Most other ecosystems are not very good at that. For example, the rainforest, which everybody thinks is a great place for fixing carbon.

[00:08:50] The problem is it turns over every year and it has about a meter of topsoil in a lot of places. The Arctic, every year you add another layer of dung dust and it freezes. And then the next year you start on top of that in the summer. And so it builds up to 500 meters. And so it's an incredibly rich ecosystem and deserts, the problem is in the deserts, everything dries up and then turns into carbon dioxide by inorganic and organic processes.

[00:09:19] So the Arctic is really quite remarkable, but we will develop technologies for measuring methane, carbon dioxide, health of the various plants and other metabolites. Essentially from very high up and, and, and so you can get, uh, you can see trends and it could all be free basically because it's all biological, uh, except for the satellite.

[00:09:43] And then I think interactome, we already use interactome for like protein interactions, but the interaction of all these zones with each other is, I think, going to be a big growth field. Interesting. When I was doing my PhD, we talked a lot about the fascinating work in writing genomes. So we're getting better and better reading genomes.

[00:10:03] We're getting better and better writing genomes. Do you think that writing genomes is relevant here? Talking either about biome scale things, or are there direct applications to what we might call climate biotech? I think it should almost be a reflex that we have that whenever anybody talks about reading, you should say writing.

[00:10:23] Because to a certain extent, reading by itself is not an action, it's not actionable, it's not, it's actionable, but it isn't an action. For example, giving patients a bunch of diagnostics that tell them how they're going to die and how they're screwing up their life isn't as good as telling them what to do right, preventative medicine.

[00:10:46] Maybe even curative. So that's on the synthetic end of the spectrum. Same thing for the environment. It takes a great person like Al Gore to tell us that things are going badly or to amplify the message. But we really need to know how do you do that. And inconvenient truths don't actually motivate people as much as convenient solutions.

[00:11:08] That's what we should be seeking. It tends to be synthetic and probably tends to be biology. I love that. And from my experience, just hanging out with people all across the political aisle, my experience is that nobody doubts problems anymore with planet, with kind of planetary health issues, but people are skeptical of solutions.

[00:11:28] So it is nice to be oriented to say, let's just build things and show that they work. And on that note, we think a lot about what the future of biology is and the language that Paul and I use is that the potential, the upper bound of biology is that it's atomically precise and infinitely scalable. Well, obviously we're far away from both, at least infinitely scalable.

[00:11:47] And I think it'd be fun just to unpack both of these with you, just to explore what does it mean for biotech can be atomically precise and infinitely scalable. And I think that the chunkier one is infinitely scalable. And one way that my former startup self thinks about things is that I think in capital expenditures, CapEx to build a factory that makes concrete, it's a hundred million dollar machine that you have to build before you can even start making concrete.

[00:12:12] If we ever master biology, we could imagine these zero CapEx big solutions where you just plant something and it grows. I know it grows to a factory or release a microbe and it cleans up all the PFAS in a mine or something like that. But we're obviously really far away from that. And then people push back when we say infinitely scalable biology, people also say, Oh gosh, it sounds like bioterrorism to me.

[00:12:32] How can that be a good thing? So it is just, I'd love to just shake your tree of knowledge. So when we talk about infinitely scalable biology, what's holding us back? And can you imagine milestones along the way up this exponential curve? Yeah. So to some extent, It's already been scaled to the entire surface of the planet without much help.

[00:12:52] We have influenced it tremendously, not in ways that everybody accepts as positive. For example, we've converted almost all the animals on the planet into, I think, 96 percent of them are domesticated in some way or another. But the point is we are engineering on a planetary scale, whether we are entirely in control of it or not.

[00:13:14] 96 is a very big number. Present that to our ancestors 10, 000 years ago, they weren't necessarily even doing agriculture. They were just harvesting semi non poisonous plants. But the point is, what are the barriers and how are you overcoming them? I mean, I think a big step was having GMO crops. Those are accepted by a surprising number of countries considering scale that they're at, and then now GMO animals like salmon and these.

[00:13:47] Are not entirely restricted to where they go. That was one of the concerns is the GMO crops would produce pollen and the salmon would produce sperm and, and they can't really stop these things easily. But I think we're getting more comfortable with it in particular with cisgenics as opposed to transgenics.

[00:14:02] Transgenics, we were moving a gene from one organism to another. And even though a lot of us don't think that's super hazardous, cisgenics seem to be from a policy standpoint, much more palatable. Also, when the innovations come from a diverse set of non monopolies, that's less threatening to say than a big monolithic American Monsanto.

[00:14:28] So there's a bunch of things that I think are moving in the direction. Also, anything that's aimed at ecosystems, saving us from climate change, tends to get much more credibility than something that's just aimed at. Improving the profit margin for seed manufacturers or something like that. And so I hear a lot of people.

[00:14:52] That we're uncompromisingly against big agro business being quite open minded to ecologically inspired conservation that, that involves new molecular technologies. I'm part of a little group called revive and restore, for example, that is Stuart Branton, Ryan Phelan and others that is, that recognize that this molecular revolution and said, There must be parts of it that we can use, like surveys and, and helping with breeding programs so you can just track things and then maybe saving a few endangered species like the black footed ferret.

[00:15:35] And so I think that's taking off too. So we see a lot of these things taking off. To go back to this idea of working across scales, and I don't know if I've, I've said this already, but Paul Reginato has this great quote of when we worked in neuroscience, we worked on things that are too small to see, and we were, and we work on climate, we work on things that are too big to see.

[00:15:53] And so when we scale that up and starting from molecular engineering first. We think about building proteins for the single protein scales pretty badly so far in the way we've, we scaled things up with a few notable exceptions. And so I think about this idea of if you take a biotech lens first, you think about doing molecular solution and then that so far, I just don't see us having a good path infinitely scalable, right?

[00:16:17] Like we can screen billions of variants of a protein, but aside from corn syrup and laundry detergent, we haven't really scaled that up. So this is one of the provocations I think about, and I'd really love to hear you respond to it, is I think biology is really good at discovery, but in terms of using a discovery, it hasn't been very good at scale.

[00:16:38] And so just hearing more kind of your thoughts on that and maybe just how we can think about making things at scale and kind of biotech would be really interesting. I think we need to embrace our exceptions because the exceptions are telling us it's like Gibson said that the. The future is here, it's just not evenly distributed and would add to laundry detergent, which is subtle isin or enamelase and those kinds of enzymes there, uh, those are adding catalytically.

[00:17:07] So their scale is actually bigger than the amount of protein made, but there's some where the protein itself is the product like antibodies, which is one of the fastest growing, uh, sectors of pharmaceuticals. And we now make, I think, on the order of 30 tons of, uh, antibodies, uh, a year. So it's, uh, these things are scaling.

[00:17:28] So, uh, and also some of the products are not proteins or enzymes. They're, they're organisms, plants, and animals. And those are scaling pretty well. Yeah. I said what fraction of our planet is now covered with domesticated animals and a similar number for the plants that is scaling. Another way of looking at the scaling is.

[00:17:49] We are not really counting how many tons of large scale integrated circuits we have. We're more obsessed with how many transistors there are in each large scale integrated circuit. So it's scaling down in size, up in complexity. And I think that's something that biology does incredibly well. And your preface to this whole thing is we're doing both.

[00:18:12] We're scaling up in to ecosystem size and nanometer scale precision. I really like that. I'm going to push one more on this idea of biology is good at discovery, but maybe not scaling the way we try to force it to scale. So the way we might force it to scale and what we have today would be some sort of chemical synthesis.

[00:18:33] So, we screen our billions or more variants of some protein, and then, do you see any world where we say, actually, we can just recapitulate that protein's function in some abiotically synthesized way and then we scale kind of artificial enzymes? Or do you see a path more on the everything discovered in biology and then scaled as biology?

[00:18:53] You won't find me say something's impossible very easily. It's totally possible to scale from a protein down to something that's maybe a little more compact. But I think it's a false economy, even though it's possible. I think that the trend is probably towards more complex things, not simpler things.

[00:19:10] And the, the urge to make everything simple is back from the era when we couldn't compute, where we had to use our fingers and toes to compute. And so we wanted everything simple and that extended through the Renaissance and the even World Wars where physicists that would come up with simple equations like F equals MA were that was the real, that was the real deal.

[00:19:35] That was exciting. And now we're in the world of complex systems, eco cosmic systems, surface chemistry and things like that, that are not where the complexity is the end, not the nuisance. I like that. I think it's a good way to skip over it. So let's leave the infinitely scalable kernel behind and instead focus on the atomically precise.

[00:19:56] So biology's upper bound is that it can be atomically precise. I would say in some ways it's natively there and we already have atomically precise tools. But how do you think we're doing overall with engineering and atomic precision? Is there still more to go, or there's certain corners that are hard and valuable that people haven't even tried yet?

[00:20:14] There's an infinity there, things we haven't tried yet, but I think we're going through a super exponential phase. So there are little moments where things go faster than the previous exponential. And then they'll maybe keep that up, maybe not, but we're in what I call MLML, machine learning with a multiplex libraries.

[00:20:33] So we already have the atomic precision of the biosphere. It's like a gift. It's like somebody from another galaxy landed a spacecraft full of great stuff. And the great stuff is of course complicated and it doesn't come with a manual, but. It's great enough that it self assembles and it does stuff for you.

[00:20:52] So we have that and we just need another tool that helps us create manuals, create variations on those, those GIFs. And that's the machine learning plus these multiplex libraries, the machine learning, then neither of them are perfect by themselves. Machine learning doesn't perfectly predict exactly what to make and the multiplex libraries are fairly useless if you're making random libraries, but you put two together and now you can explore trillions of designs.

[00:21:21] And this is literally the scale that we're on now is we make trillions of complex atomically precise proteins that almost all of them do something and you just have to figure out, find the pairing between what you want and what you've got. Okay. I want to hover on that for one more second, because right before we clicked record, we were talking about the phrase inorganic synthetic biology, and that feels like we're stepping towards that.

[00:21:46] And so we'd love to just shake this, the, the tree of George's knowledge a little bit around this corner, um, of atomic precision and then towards inorganic synthetic biology. And so we just would love to hear you unpack this new area and why we might focus on that. The old part of the new area is that you've got all kinds of inorganic materials that.

[00:22:06] That the average biologist might ignore, depending on their field. But things like nanomagnets that are used for orienting relative to the Earth's various axes. Diatoms have these exquisitely complicated, uh, silica based structures. And there's calcium based minerals. And, uh, you use manganese and molybdenum and all kinds of things you don't Early students don't think about much, but they're critical components of things like disputase and so forth.

[00:22:39] The question becomes not what, what's the next element of this periodic table we're going to add. It's, are there any that were, that aren't already in, in our biosphere collection of things that we can build our little tools, tool set. And some of them could be added at this point from, from first principles.

[00:23:01] And these large libraries and you can get, you can make little protein motifs that will selectively bind one element or another or a few in a specific configuration. And you can start collecting configurations before you even know what they're good for. And you can start using them for making meta configurations where you take.

[00:23:23] Two atoms that are close to each other and another two, and then you can now four and so forth. And we don't know exactly where it's going, but it's the present is there. And biology is naturally three dimensional. The microfabrication world is still poking around at about 30, 40 nanometers. They call it the three nanometer revolution, but I don't, they, they just started an arbitrary scale that isn't actually representing where they are.

[00:23:53] But it's more like 30 nanometers. Biology is tinkering around sub angstrom level. There actually are enzymes where sub angstrom matters and it's been optimized at that, at that level and it's 3D, not just 2D. So I think we're a very interesting place now for the inorganic or synthetic biology. Well, I never want to be one to miss a good joke and we could have been trolling the semiconductor people for decades, huh?

[00:24:20] Oh, not too late. Not too late. Cool. George, thank you so much for giving us a survey on the biotech world and how it might apply to climate. I'd love to pass it over to the science director of Homeworld, Paul Reginato, also co founder of Homeworld, too, because he'd love to guide some questions around Uh, specific climate relevant problems.

[00:24:38] We'll do this for about 20 minutes, and then we'll wrap up with questions from the audience, uh, and some rapid fire closeups too. So Paul, please jump in. Thanks so much, Dan and George. It's been fun to listen to you chat so far. George, when we think about applying biotech to sustainability, there's a lot of different possibilities.

[00:24:59] And in some of those, in some of those examples, let's say manufacturing or mining, there are other technologies that might come in chemistry. And the solutions may not wind up being biological, but for some of the problems we have, it really seems like they're intrinsically biological. For example, landscape emissions and removals.

[00:25:19] There are concerns of runaway landscape emissions of methane from wetlands or permafrost and regeneration of degraded land, on the other hand, could support biodiversity and sequester carbon. And Also just for maintaining robust biodiverse ecosystems when we have things like invasive species happening, we have all these new pressures applied to ecosystems.

[00:25:43] Are there ways you imagine us dealing with some of those challenges? I think de extinction in particular is one where it sounds really hard. The goals are typically less than de extinction. And the means are closer than they look. For example, what we really want might be some cold tolerant animal that will shift the balance slightly from trees to grass, as it was before.

[00:26:14] Grass being more productive photosynthetically, better at trapping the carbon and allowing herbivores. To hound down the snow in the winter so that you actually get good freezing of the permafrost. And so that isn't necessarily the extinction and the tools aren't necessarily hard. Could be. We have beavers that will knock down trees.

[00:26:40] That was a big deal in Yellowstone after they reintroduced the wolves that resulted in a lot of beaver activity. If we had cold tolerant beavers, that would be one possibly, or maybe bison. Bison are almost big enough that they can knock down the wimpy little trees that grow in the Arctic or elephants, but elephants, that isn't the extinction.

[00:26:59] That's just making them cold tolerant. And where are we on the range of engineering? Plants and animals, we're getting into the point where we think that 69 edits in the germline of pigs is no big deal, uh, we now have livers and kidneys from being donated by pigs that have been engineered at 69 locations in the genome.

[00:27:23] I think for plants and animals, we're pushing up into the hundreds of edits and maybe even synthesis. So then you start thinking of it, so that's from the bottom up, what are our molecular limitations and species limitations coming down is what kind of ecological gadgets would we both want and feel comfortable with.

[00:27:44] And I think mega herbivores, we actually feel pretty comfortable. Let's say more comfortable than say putting nano scale gene drives into. Millimeter scale insects, which are highly prolific that offers great promise, but it also causes pause, but we know that we can get rid of mega herbivores because we did it on the, in the Galapagos where goats were introduced by some of the early sailors and they started stepping on ecotourism, a valuable egg and hence the goats were removed by the Ecuadorian government.

[00:28:21] So I think that engineer animals are clear that apex predators and other mega herbivores have a outsized effect on the environment in a good way, in a way that where you can have a lot of leverage with a small number of animals. That's what happened again in Yellowstone with the wolves, elephants and other large herbivores could do the same thing for the Arctic.

[00:28:45] So we've had a bunch of questions here for you so far on ideas that we've come up with to prod you on. And are there other areas of. Applications of biology to problems in climate sustainability that you're excited about, or I think we're worth sharing with our audience. One, one. That thing that, that I have, I think cuts across a number of different needs, societal needs is ability to do total recycling.

[00:29:14] We have, we've toyed with this for decades, going back to this early submarines and early space stations and whatnot, but we've never actually done it. There's. The closest we've come is around six months before we need to have a resupply. And plus jettisoning a bunch of waste, uh, without worrying about where it's going.

[00:29:36] You add it to the waste belt that's building up us orbiting the planet. And I think that the ability to do total recycling not only is inspiring, because that's what we're trying to do is keep the microplastics out of the ocean and so forth, but it has at least three bona fide applications. One is. If, if we're serious about space colonies, we need to be building colonies on earth.

[00:30:00] It's just too risky to have our first rodeo on Mars. And then if it goes wrong, then it's eight months to two years to get back to the nearest emergency room. While if we have lots of practical, useful colony like things on earth, then de risks the interplanetary, but it also could help us with things on earth that might be problem, there might be.

[00:30:25] Lots of situations where supply chains are problematic, either locally or globally. Um, be nice to have something that doesn't depend on supply chains. If you have any source of energy, you can convert that into biomass. And, and I've recently been joined by, I think one of the world's experts on this, Elizabeth Hahn, who I think is really pushing this frontier and supply chain space.

[00:30:50] Maybe even reducing the footprint of, of farms so we can restore that to natural environments. It's interesting that you've got doubling times that, that are. You know, on the order of 15 to 90 minutes in some kind of biological replication and compare that to things on, on the farm, which are 17, 000 times or depending on your units.

[00:31:20] And so that's maybe indicates that you could shrink the size of, of your farms to something that would fit in your kitchen. These are, these are, this is an example of something that I think is worthy of further scrutiny. Can I push on that one for a sec, the idea that you could have a, you could have a farm inside your kitchen and you're converting energy into biomass really rapidly, right?

[00:31:47] How does that work? So it, it is premised on having some source of energy. Now, it could be you get, you're competing with the same. Photons that providing the farms and it recognizes that photovoltaics is more efficient as much as I love photosynthesis being a biologist, photovoltaics is more efficient.

[00:32:09] You have to keep into it the full life cycle, the full LCA analysis, but you're pushing up 20, 30 percent efficiency while photosynthesis is really hard to push past 3%. And the wavelengths are broader too, the photovoltaics will go from UV to infrared, while plants have really, typically very sharp bands at red and at blue, and not even green.

[00:32:34] And so you can convert the photovoltaic into other forms of energy that It might be compatible either with photosynthesis or with heterotrophic biosynthesis. And then you're just programming it to make things that taste good, are nutritious, or, or, or, or the basis for manufacturing goods that are not edible.

[00:32:57] So I think I'm a little, I know that doubling time is not the only thing that's important for biomass, but it is highly correlated and it's a good starting point. Um, in this, you know, at least a thousand fold range between things that are considered practical today on farms and what is practical today in, in a lab, a thousand fold should be harnessed and, and allow us to shrink our farms and shrink our dependence on supply chains, which are very energy intensive and subject to disruption in a variety of ways.

[00:33:31] I have one more question here before we're going to switch to questions from the audience. And I just want to end with a question on, you're, you're known for, for having insightful ideas about how, uh, technologies could be applied in the future and also for developing novel foundational technologies that get us there.

[00:33:50] And so I'm curious if you could encourage folks to think about new foundational problems. What's even just one problem that you would recommend people consider working on the level of foundational enablement for future technologies? Uh, yeah, good, good question. So there's plenty to do on variations on themes.

[00:34:10] So I want to take something that's a little more radically departed. So I think that we're getting pretty good at programming matter. Ranging 3d printers, I think are, are pretty good at placing things. You can place things as small as atoms with a, with atomic force microscope. It's very, not exactly the way you should manufacture anything yet.

[00:34:32] You could place cells, which are much, much bigger, but it's pretty coarse compared to the precision that cells are placed biologically. And it's typically you're placing things on the order of a hundred micron resolution while cells in vivo are more like five microns. And so I think I'm inspired by developmental biology.

[00:34:53] Where instead of having one print head that's moving as fast as it can, or maybe even light based systems where you can have a megapixel per layer going up one layer every second or so. In biology, those are, those are like amateurs. You can have trillions of printheads cubic millimeter in the form of ribosome is essentially a printhead that's printing and you don't have one ink or two inks or you have millions of different kinds of inks, the inks being different RNAs and proteins and carbohydrate polymers.

[00:35:30] So I think we need to get better at harnessing developmental biology. So, to some extent, we will simultaneously harness it and understand it, and we don't, doesn't have to be understanding first, um, simultaneous. My favorite example is vaccines, the, uh, cowpox and, uh, rabies vaccines. We didn't know what a virus was, didn't know what immune cells were, any of that stuff, but the protocols that were developed were pretty much the same ones we used in the early 21st century.

[00:36:03] So, I think. Developmental biology would be really great, not just because so many things that we care about go through developmental biology, human babies growing up and aging as part of the developmental process, but also because developmental biology is an alternative to other forms of 3D printing. So I think that.

[00:36:24] And then just a variation on that, but pretty big one is behavioral biology. I think we need to learn how to program behavioral systems, which means we probably need to program connectomes, which is like the ultimate difficult problem in developmental biology, because not only do we have to have these trillions of printheads per cubic millimeter, but we need to have this, these connections where you might have 10, 000 connections per neuron.

[00:36:51] And you either want to let them wire up semi randomly, but then take on meaning, or we might want to go beyond biology and wire them up, you know, with, with predetermined specificity that's greater than any biological system. So anyway, those, those would be the two highly related things that we should be spending more time on.

[00:37:14] Thanks so much George. So I'm going to hand it back to Dan now, who's going to, I think, steward some questions from the audience. All right. So we have 10 more minutes. And so we're going to play a rapid fire. Set of questions. First question from the audience is what's your front runner organism for kitchen scale farms?

[00:37:31] Oh, I don't think there is one yet. I think that our front runner metabolite for the time being, and this is subject to change too, is acetate. So there's, just think of things that, that factor and consume acetate as an interview. So you can make, manufacture it inorganically and then use it as a carbon source, a reduced carbon source for.

[00:37:54] A lot of other things. Second question. Do you think it would be good to get more PhD bioscientists and leading venture capital firms? Probably not a bad idea. I think it's interesting to PhDs. That's the important. You want both the industry to be happy and the individuals to be happy. I think that's possible.

[00:38:12] I find that a lot of venture capitalists know so little about subject matter. They're basically making decisions based on body language and. Whether they like the bluff or they don't like the bluff, they know it's bluff, but they just, whether they think it'll sell or not. And I just really don't think that's in the best interest of the society.

[00:38:32] But it is working. Yes, to some degrees of working. It's a mere world worth the risk. That's a big topic. It's a small topic and almost nobody talks about it, but I would say it's not worth the risk in a replicative sense. But it's definitely, there isn't much risk if we talk about making mirror proteins without replication that very predictably will do reactions.

[00:38:58] It's the very few opportunities where you can say, if I make this sequence, it'll do exactly this reaction, exactly this rate with exactly these cross reactions and so forth. But you can do that with mirror enzymes. And also their ability to persist in, in, in human systems and ecological systems without replication.

[00:39:17] Rapid turnover. So as long as it's made completely as far as possible from replication, I think it's safe and we should consider it. But we need to, as with many other technologies, we need to have safety first. Uh, almost every engineering discipline has safety. Engineering is one of its things like the UL is the safety for electricity.

[00:39:38] And the, we have certification for people that build bridges and buildings and so forth. So I think we need, this is one of those fields. All right, we'll keep moving forward. So one of the things that everyone loves about you is that you go out of your way to encourage curiosity and people work both directly and indirectly with you.

[00:39:57] So I want to explore this for a second. What is one line of advice you find yourself giving a lot? Having to do with curiosity. For, or just in general, as you, as a mentor for the people that get to work directly with you. Is there a theme in the advice and feedback you give people that work for you?

[00:40:14] There are a few. I think that people sometimes. Penny wise and pound foolish. Most of these things, they're obvious once you state them is you'll try to, you'll be trying to save a hundred dollars on experiment when you're holding society back by a trillion dollars or your, or even your own time is worth more than that, things like it's easier to come up with these pithy aphrodite when, when somebody presents you with a problem.

[00:40:42] Um, anyway, that, that, that's one off the top of my head. Got it. But there's a question that's come up as well, which is, and I think you've already answered it, but for people who are looking to do graduate scale or undergraduate level work in biotech, what are a couple areas you might shine the light of areas to be curious in for bio?

[00:41:03] We mentioned a few, uh, already like inorganic developmental biology, synthetic behavioral. I think there's a lot to be determined with bio mining, just going through. The databases that we have, there are no doubt hundreds of cool machines out there that are even cooler than polymerase and ribosomes and CRISPR and restriction enzymes and so forth.

[00:41:29] That's a place to look. Don't be scared by the fact that nobody else is looking at it. Sometimes that's a good sign. Not just, sometimes it's a bad sign, but there, there's some really There's a lot of weird things that, that, that work out. For example, Tom Cech was studying tetrahymena, which is a pretty obscure protists at the time.

[00:41:53] And he discovered two things in tetra. He and his colleagues discovered two things, which was telomeres and ribozymes. Not a bad harvest from previously almost unknown protozoan, but yeah, places to look. There's a metaphor there with surfing. When you're the only person out in a wave, it either means you beat everybody there or there's sharks in the water.

[00:42:20] Don't kill that many people, you could probably surf with a prosthetic leg on that perfect note. I want to say George, um, both to, to Paul and I personally, you've been a fantastic mentor. You can draw a very direct line from your influence on us to what created homeworld and created this community of climate biotechnologists.

[00:42:36] So we're really grateful for your influence on us personally, and then taking time to share your perspective and just getting a chance to geek out quite freely on a bunch of very wide ranging topics. So we're right at the time. I want to say a huge thank you to George. I would ask, normally they would ask guests, how did they find you?

[00:42:53] It's quite easy to find you online, George. So just want to say everyone to the audience here, just say a huge thank you to George for taking the time. Thank you very much. Thank you all. And I love what you're doing for society. Keep it up.

[00:43:11] Iran what do you think of that episode?

[00:43:12] Erum: wow, that was incredible. I had to put my, Deep bio and chemistry had on, he talked about different molecules and, I wish I had,

[00:43:22] Erum: chat, you'd be to or perplexity. now that is integrated with deep seek. while I was listening to it.

[00:43:27] Erum: But lo and behold, I was going for a walk and I just wanted to. Do pure listening experience away from the screen. But wow, I love the way that Dan and Paul framed the questions. it's also cool that they record their podcast, in a form of a webinar where they have an audience that's watching this conversation happen live and they could submit questions.

[00:43:46] Erum: but there were a lot of interesting. Concepts that I think would be worth highlighting our outro here.

[00:43:52] Karl: one thing I would say is what I remember is when John covers and I interviewed George for what's your bio strategy? He actually had one of the more controversial Interviews in the book because he talked about doing CRISPR on the human germ line Which is something that no one was talking about and at that point he was saying that that's going to really be some of the first applications beyond disease, , and that we would expect to see that pretty fast and given that the book is now seven or eight years old, we're probably coming up on that very quickly,

[00:44:19] Karl: one of the things he highlighted is that he said that more people need to do bio mining.

[00:44:24] Erum: And for us, when we talk about bio mining, we're talking about using biology to mine rare earth minerals or different. metals, in the ground as like an extraction process, but he actually meant bioprospecting, which is how we describe the act of looking at different biology to find unique functionality or tools.

[00:44:46] Erum: so he was like, we found CRISPR, we found GLP and, these organisms, but there's so many more out there. So we need to mine biology to find this functionality. at first I was like, Oh, he's gonna talk about by mining. But no, no, he's actually talking about by a prospecting, which I think goes to show that we do need to come together on how we talk about different things.

[00:45:06] Erum: so we're more clear as an industry, as a discipline. but it's fine. he followed it up with context no one was harmed.

[00:45:16] Karl: So what else stood out to you in this episode? There was a lot.

[00:45:19] Erum: George also talked about something very interesting that, we're going to dig into in a future episode, but he was saying that we need to make space colonies on earth. So looking at where on earth is a good place, I mean, we do have lots of barren land on earth, to de risk Mars colonies. And that way we can come up with solutions that can not only be applied for Mars colonization, but it can be applied on earth. And we can just. Take it. this whole concept of total recycling or, we talk about circularity within a colony.

[00:45:51] Erum: What does that look like?

[00:45:53] Karl: Yeah, it's super interesting because that is something that, Andrew Hessel talks about. Andrew Hessel talks about these underground cities. He believes that, we need to be thinking about moving underground. in the Genesis machine, he has a whole chapter about, Tesla or SpaceX, creating this prize for people who form these colonies that are able to live underground, which would be a great testing ground for Mars.

[00:46:17] Karl: There are all these abandoned mines all over the place. And those could be a starting point for this, but I love that idea. as you said, we're going to have an episode very soon where we talk about some of the challenges that are faced by those who want to go to Mars. There's a lot of them.

[00:46:32] Karl: one thing I talk about in that episode, which I'll just preview here is a few years ago, Craig Venter talked about sending a DNA printer or biological printer to Mars before we send anybody, which makes a lot of sense because then you could be printing. Bacteria, from a distance and using those bacteria to do useful things in advance of sending humans to Mars.

[00:46:54] Karl: So I think that doing these space colonies underground or somewhere in the Atacama desert makes a lot of sense.

[00:47:00] Erum: there was a lot. , because was taking notes as I was listening, not, consulting perplexity, but, , he gave a shout out to revive and restore, which he is also affiliated with, which makes a lot of sense because they use genetics to, D in danger, I guess. I mean, they haven't really D extincted an animal yet, but they're animals that are endangered, like the black footed ferret and the passenger pigeon, which we had been Novak on this Podcast who is part of revive and restore and he did a great job storytelling about the passenger pigeon.

[00:47:31] Erum: So highly recommend people listen to that episode. cause he's on the board of all these companies. He has so much perspective. will just say the, final thing that really stood out and the statement, I think, we need to cut it up and, share it with home world, share it with everyone, is this idea of scaling up to the ecosystem size with nanoscale precision. That's what we're talking about when we're talking about, biotech or bioengineering to be able to create impact on our ecosystem scale, the scale at which we work, whether it's within our bodies, which is a whole ecosystem, but of course, within our communities, within our regions, scaling up one thing globally can happen if you think about a decentralized, structure, but what do you think about that term?

[00:48:21] Erum: Like, what do you think about, how he introduced some of these concepts?

[00:48:24] Karl: what, I've heard people say, and I repeat it, biotech is nanotech that works. and I like to remind people that, biology works both on the nano scale where it's atomically precise, but also on the macro scale when we look at whales or redwoods, which are the biggest organisms.

[00:48:42] Karl: On the planet. So biology has this beautiful ability to work at these different scales. So when George says, we need to scale up Ecosystem size, with nanoscale precision. I totally see that happening, and that's really part of what we're trying to talk about here on the Grow Everything podcast.

[00:48:59] Erum: Yeah. Yeah. so for all of you out there that are writing grant applications and pitching, maybe you want to put that statement in there. Let's, unify and talk to all the funders, whether it was venture capital or philanthropicthose are some good terms.

[00:49:13] Erum: , ,

[00:49:14] Erum: so with that, one other thing I wanted to share is that the Homeworld Collective is putting out another fund towards bold ideas and greenhouse. Gas removal. So if you have any projects in that space, you want to reach out to the home or collective. you can reach out to them at homeworld bio slash grants.

[00:49:31] Erum: , these grants range from 50 to 150 K and. We know a lot of creative people that have solutions to remove greenhouse gases, things like bio enhanced rock weathering or atmospheric methane removal, or just some ideas. So reach out to them, get some money and fund your project and let's make things happen.

[00:49:51] Erum: Who knows? Maybe you'll be the next person on the grow everything podcast.

[00:49:54] Karl: Yeah. Well, thank you again, Homeworld Collective, and thank you to our listeners for, always listening and participating. if you have any questions or comments, please call in the grow everything hotline The number is in the show notes get in touch with us. We love us. We love you We love us.

[00:50:11] Karl: We love you

[00:50:12] Erum: Love fest.

[00:50:13] Karl: and make a pro move become a patreon and become a part of the grow everything community.

[00:50:18] Erum: Awesome. That's the pot.

[00:50:19] Karl: See you later