How Microscopic Innovations Can Scale Global Solutions with George Church

On this episode of The Climate Biotech Podcast, we're sitting down with the legendary George Church. A pioneer in genomics and synthetic biology, George is known for his innovative visions for future tech — and for developing the foundational tools to get us there. 

This conversation spans a gamut of creative ideas including observing planetary metabolomes with satellites, cleaning up supply chains via total recycling, advancing inorganic synthetic biology using multiplex DNA libraries, and harnessing developmental biology to surpass current 3-D printing capabilities.

Tune in to hear George's unique perspective on how biotechnology can provide infinitely scalable and atomically precise solutions to our planet's most pressing issues.

(00:00) Introduction to the Climate Biotech Podcast
(02:26) Meet George Church: Early Life and Career
(04:23) The State of Synthetic Biology and Bioengineering
(06:13) Future -omes and Planetary Scale Biotech
(08:47) Writing Genomes and Climate Biotech
(10:22) Infinitely Scalable and Atomically Precise Biology
(20:38) Inorganic Synthetic Biology and New Frontiers
(23:26) Paul Reginato's Segment: Climate Relevant Problems
(36:13) Audience Q&A and Rapid Fire Questions
(41:17) Closing Remarks and Thank You

Chapters

• 0:10 Climate Biotech Innovation and Future Goals
• 6:59 Biology and Climate Biotech Scalability
• 22:23 Biotech Applications in Climate Sustainability
• 28:33 Future Biotech Applications in Agriculture

Transcript

[00:00:00] 

Daniel Goodwin: Welcome to the climate biotech podcast, where we explore the most important problems at the intersection of climate and biology, and most importantly, how we can solve them. I'm Dan Goodwin, a technologist who spent years transitioning from software and neuroscience to a career in climate biotechnology.

As your host, I will interview our sector's most creative voices from scientists and entrepreneurs to policymakers and investors. 

This is so exciting. For us, for Paul Reginato and I, we both did our PhDs with George Church. We are part of a large community, people that have been mentored by George, and it was a very fun eclectic group of us.

The one thing that I really hope we get everyone to experience today is George's ability, not only to set the standard of technical excellence, but also to encourage [00:01:00] creativity and encourage people to think big. One of the things about George that's always just, frankly, blown my mind is his ability to span so many orders of magnitude in a single conversation.

He'll go everything from, single enzyme turnover, kinetics, to talking about, millions of years of evolution. He'll talk about Angstrom level behavior, and then he'll talk about Parsec level biology. It's going to be a really fun conversation, and the best thing that I personally can do in this conversation is really get out of the way as fast as possible.

But to set a little bit of intention here we're very happy to have George Church, a professor at Harvard Medical School, joining us for the first part of the conversation. I will ask some of the questions and then I'm going to get out of the way to let Paul Reginato also ask some questions to George. The goal of this is to be a pretty fast paced 45 minutes or so. For everyone to just get to learn how George thinks and talk really about some of the bigger, higher level questions here in biotech, especially in a downswing in the market, [00:02:00] one note I'll say from my meetings with George is I did my PhD is that I would take extensive notes talking with George, and then I would live off those things for about two months, where I would make some progress in the lab and I go back and then George had this one little side comment was on paper from 1981 end up having the exact answer I needed.

And anyway, I hope everyone gets the same joy I did from doing our PhDs with George and also I hope we all get to learn from this. So George Church, thank you so much for joining us in this conversation. Who are you? Where'd you grow up?

George Church: Yeah, this is to humanize. So I shouldn't mention the Skynet stuff. But the mud flats 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 cause I could go out and stomp around to find echinoderms and things like that.

Daniel Goodwin: Did you always know that you'd be building the future of biology as a professor at Harvard?

George Church: far from it. I didn't even have any science courses until seventh grade. And even that was pretty primitive [00:03:00] in florida. I think at one point I was planning on studying river dolphins in the amazon. The, the Pink River dolphins. I learned a lot about outboard motors 'cause I figured I'd be fixing outboard motors on the Amazon.

And I actually made it to Brazil when I was 12 or 13. But didn't actually materialize. And it's, and had to settle for what you just described instead. 

Daniel Goodwin: There is still time, George.

George Church: oh, yes. So there's lots of times since we're not gonna die. Yeah.

Daniel Goodwin: Great.

George Church: The more limiting thing is whether the river dolphins are going to die. That's more of a problem.

Daniel Goodwin: 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?

George Church: I was always unfocused you could call it or polymath is the more generous version. There was nothing, no science or math or knowledge that I wanted to abandon.

So I just kept accumulating it and [00:04:00] looking for combination and that happened. I guess sophomore year of college I found crystallography, which required, Fourier transforms of math and physics and chemistry and biology and a lot of computing.

Daniel Goodwin: 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, really like whatever you want to call it.

And I'm hoping in this conversation, we get to go into a 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 spacked or went public in 2020, 2021 down 90%. A lot of startups are laying people off. 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 I do want to [00:05:00] spend time focusing on long term goals, but you've seen a lot. You've been writing world changing paper since the eighties. 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. 

George Church: The first thing is to take Doug Adams advice. Don't panic. And second is if, the old aphorism by low sell high. 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.

The. 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. And 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 that exponential is [00:06:00] fairly gratifyingly constant,

Daniel Goodwin: I think you've been one of the leading figures of showing that biology is outpaced Moore's law, in terms of sequencing. 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 -omes in biology, right?

So we've got the genome, the transcriptome, the epigenome, the connectome from neuroscience. What are the future -omes 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 -omes and what are the -omes that we still have a lot more exponential growth in?

George Church: 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 with that. Amplify that signal and turn it into something that's reflective of things you care about.

So for example, when I [00:07:00] was in Siberia, I was up close and personal to monitoring stations for carbon dioxide and methane, because for the first, Time in, in recorded history when I was there was the first time that it, the permafrost melted and didn't fully refreeze. And there's a lot of methane being produced throughout the Arctic, not just Siberia and, 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.

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 and dust and it freezes and then the next year you have to start on top of that in the summer and so it builds up to 500 [00:08:00] 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.

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 so you can get you can see trends that you and it could all be free basically because it's all biological, except for the satellite, and then I think interactome, we already use interactome for, like protein interactions, but the interaction of all these -omes with each other is I think going to be a big growth field.

Daniel Goodwin: 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. We're getting better and better writing genomes. Do you think [00:09:00] That writing genomes is relevant here talking either about biome scale things, or are there direct applications to what we might call climate biotech?

George Church: I think it should almost be a reflex that we have that whenever anybody talks about reading you should say writing because to a certain extent reading by itself is not It's 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 to tell them how they're going to die and and how they're screwing up their life isn't as good as telling them what to do, right?

Preventative medicine, maybe even curative. So that's on the synthetic end of the spectrum. Same thing for the environment. It takes a, 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 [00:10:00] solutions. That's what we should be seeking. And that, that tends to be synthetic and probably tends to be. Biology.

Daniel Goodwin: 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. 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, obviously we're far away from both, at least infinitely scalable.

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 [00:11:00] makes concrete, it's a hundred million dollar machine that you have to build before you can even start making concrete. If we ever mastered biology, we could imagine these zero cap X big solutions where you just plant something and it grows, I know it grows to a factory 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 gosh, it sounds like bioterrorism to me. 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?

George Church: Yeah. So to some extent it's already been scaled to the entire surface of the planet without much help 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 [00:12:00] are engineering on a planetary scale, whether we. Are entirely in control of it or not. 96 is a very big number. If you were to 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 think a big step was having GMO crops. Those are, accepted by a surprising number of countries, considering the scale that they're at.

And then now GMO animals like salmon. And these, 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 it's, and you 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.

Transgenics, we were moving a gene from one organism to another. And even though a lot of [00:13:00] 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.

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 that were uncompromisingly against big agro business being quite open minded to Ecologically inspired, conservation that involves [00:14:00] new molecular technologies.

I'm part of a a little group called Revive and Restore, for example, that is Stewart Brand and Ryan Phelan and others that, 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.

And so I think That's taking off too. So we see a lot of these things taking off.

Daniel Goodwin: To go back to this idea of working across scales and I don't know if 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 when we work on climate, we work on things that are too big to see. And so when we scale that up, and starting from molecular engineering first.

We think about building proteins for the, a single protein scales pretty badly so far in the way we've scaled things up with a few notable exceptions. And so [00:15:00] 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?

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 as I think biology is really good. at discovery, but in terms of using a discovery, it hasn't been very good at scale.

And so just hearing more kind of your thoughts on that, and maybe just how we can think about making things at scale and climate biotech would be really interesting.

George Church: I think we need to embrace our exceptions because the exceptions are telling us it's like Gibson said that the future is here. It's just not evenly distributed. And it add to laundry detergent, which is subtilisin and amylase and those kind of enzymes. Those are adding catalytically, so their [00:16:00] 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. Sectors of pharmaceuticals and we now make I think on the order of 30 tons of antibodies a year. So it's These things are scaling so And also, some of the products are not proteins or enzymes they're organisms, plants and animals, and those are scaling pretty well.

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, we're 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 [00:17:00] biology does incredibly well. And your preface to this whole thing is we're doing both. We're scaling up in, to ecosystem size and nanometer scale precision.

Daniel Goodwin: 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. 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 proteins function in some abiotically synthesized way, and then we scale kinda artificial enzymes. Or do you see a path more on the, everything discovered in biology and then scaled as biology

George Church: You won't find me say something's impossible very easily. So 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 [00:18:00] towards more complex things, not simpler things and 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 to be simple. And that extended. Through the renaissance and the even world wars where, physicists that would come up with simple equations like F equals M a or that was the real, that was the real deal. That was exciting. And now we're in the world of complex systems, ecosystems cosmic systems surface chemistry and things like that, that are not the, where the complexity is the end not the nuisance.

Daniel Goodwin: I like that. I think it's a good way to, to skip over it. So let's leave the infinitely scalable kernel behind and instead focus on the anatomically precise. So biology is upper bound as 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 atomic precision? Is there still more to [00:19:00] go? Are there certain care corners that are hard and valuable that people haven't even tried yet?

George Church: There's an infinity there, things that 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 

multiplex libraries. So that, 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.

So we have that, and we just need another tool that helps us create manuals, create variations on those Those gifts and that's the machine learning plus these multiplex libraries. Machine learning, then neither of them are perfect by [00:20:00] 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. 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.

Daniel Goodwin: 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. And so we'd love to just shake this, the tree of George's knowledge a little bit around this corner 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.

George Church: The old part of the new area is that you've got all kinds of inorganic materials that the average [00:21:00] biologists 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 silica based structures and there's calcium based minerals and 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 nitrogenase and superoxide disputation and so forth.

And 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 we're, 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 and these large libraries, and you can get, you can make little protein motifs that will selectively [00:22:00] bind one element or another in 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, 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 precedent 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 just started an arbitrary scale that isn't actually representing where they are.

But it's more like 30 nanometers. Biology is. It is tinkering around sub angstrom level. There actually are enzymes where sub angstrom matters, and it's been optimized at that level. And it's 3D, not [00:23:00] just 2D. So I think we're a very interesting place now for the inorganic or synthetic biology.

Daniel Goodwin: Wow. I never want to be one to miss a good joke and we could have been trolling the semiconductor people for decades, huh? 

George Church: Oh, it's not too late. Not too late.

Daniel Goodwin: 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.

Cause he'd love to to guide some questions around a specific climate relevant problems will do this for about 20 minutes and then we'll wrap up with questions from the audience and some rapid fire close ups to so Paul please jump in.

Paul Reginato: 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. And in some of those, in some of those examples let's say manufacturing or mining there are other technologies that might [00:24:00] 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, 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.

Are there ways you imagine us dealing with some of those challenges?

George Church: I think de extinction in particular is one where it sounds really hard, but the goals are typically less than the extinction, and the means are closer than they look. For example, what we really want might be some cold, tolerant [00:25:00] animal that will shift the balance slightly from trees to grass, as it was before.

Grass being more productive photosynthetically better at Trapping the carbon and allowing herbivores to pound down the snow in the winter. So you actually get good freezing of the permafrost. And so that isn't necessarily the extinction. tools aren't necessarily hard.

It could be we have beavers that will knock down trees. That was a big deal in Yellowstone after they reintroduce the wolves that. resulted in a lot of beaver activity. If we had cold tolerant beavers, that would be one possibility, 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 that's just making them cold tolerant. And where are we on the range of engineering plants and animals? We're [00:26:00] getting into the point where we think that 69 edits in the germ line of pigs is

no big deal. We now have livers and kidneys from being donated by pigs that have been engineered in 69 locations in the genome. , I think for plants and animals we're pushing up into the hundreds of edits and maybe even full 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? 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 [00:27:00] Galapagos where goats were introduced by some of the early sailors and they started stepping on Eco tourism valuable eggs and hence the goats were removed by the Ecuadorian government.

So I think that engineer animals are, it's 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.

Paul Reginato: 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. 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.

George Church: One, one pet thing that I have I think cuts [00:28:00] across a number of different needs, societal needs, is ability to do total recycling. We have, we've toyed with this for, decades going back to the early submarines and early space stations and whatnot, but we've never actually done it.

There's. The closest we've come is around 6 months before we need to have a resupply and plus jettisoning a bunch of waste without worrying about where it's going. You add it to the waste belt is building up. 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 bonafide applications. One is if we're serious about space colonies, we need to be building colonies on earth. It's just, Too risky to have our first rodeo on Mars, and then if it goes wrong [00:29:00] 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 and the risks of the interplanetary.

But it also could help us with things on earth that might be problem. There might be lots of situations where supply chains are problematic either locally or globally. 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 I've Recently been joined by, I think, one of the world's experts on this Elizabeth Han, who I think is really pushing this frontier. And supply chain, space, earth. Maybe even reducing the footprint of farms, so we can restore that to natural environments that it's interesting that you've got doubling times that that are, you know, on the order of 15 to 90 [00:30:00] minutes in some kind of biological replication and compare that to things on the farm, which are.

17, 000 times or depending on your units. 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, this is an example of something that I think is worthy of further scrutiny.

Paul Reginato: Can I push on that one for a sec idea that you could have a. You could have a a farm inside your kitchen and you're converting energy into biomass. really rapidly, right?

How does that work?

George Church: So it, it is premised on having some sort of energy. Now it could be you get, you're competing with the same photons that are providing the farms, and it recognizes that photovoltaics is more efficient. As much as I love photosynthesis, being a biologist, photovoltaics is [00:31:00] more efficient. 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 percent.

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 and so you can convert the photovoltaic into other forms of energy that, that might be compatible either with photosynthesis or with heterotrophic biosynthesis.

And then you're just, programming it to make things that, The taste good and are nutritious or the basis for manufacturing goods that are not edible. 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 in this, [00:32:00] at least, A thousand fold range between things that are considered practical today on farms and what is practical today 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.

Paul Reginato: So 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 technologies could be applied in the future and also for developing novel foundational technologies that get us there.

And so I'm curious if, 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.

George Church: Yeah, good. Good question. [00:33:00] So there's plenty to do on, variations on themes. 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. 3D printers I think are pretty good at placing things.

You can place things as small as atoms with a atomic force microscope. It's very, it's not exactly the way you should manufacture anything yet. You can place cells, which are much, much bigger but it's pretty coarse compared to the precision that cells are placed biologically. It's typically you're placing things on the order of 100 micron resolution while cells in vivo are more like, Five microns and so I think I'm inspired by developmental biology 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 [00:34:00] are like, Amateurs you can have trillions of printheads per 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.

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. It's simultaneous. My favorite example is vaccines.

The cowpox and rabies vaccines, we didn't know what a virus was, didn't know what immune cells were or any of that stuff. But the protocols that were developed were pretty much the same ones we used. In the early 21st century. So I think developmental biology would be really great. Not just [00:35:00] because so many things that we care about go through developmental biology.

Human babies growing up and aging is part of the developmental process. But also because developmental biology is an alternative to other forms of 3D printing. So I think that, and then just a variation on that, but a 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 And these connections where you might have 10, 000 connections per neuron 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

with predetermined specificity that's greater than any biological system. [00:36:00] So anyway, those would be the two highly related things that I think we should be spending more time on.

Paul Reginato: 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.

Daniel Goodwin: 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?

George Church: Oh I don't think there is one yet. I think that our frontrunner metabolite for the time being and this is subject to change too, is acetate. So there's, so just think of things that, that manufacture and consume acetate as a, so you can make, manufacture it inorganically and then use it as a carbon source, a reduced carbon source for a lot of other things.

Daniel Goodwin: Second question, do you think it would be good to get more PhD bioscientists in leading venture capital firms?

George Church: Probably not a bad idea. I think it's interesting to PhDs. That's the important, you want both the [00:37:00] industry to be happy and the individuals to be happy. I think that's possible. I find that a lot of venture capitalists know so little about the subject matter that 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, so whether they think it'll sell or not, and I just really don't think that's in the best interest of the society, but it is working 

Daniel Goodwin: Yes, to some degrees of working, it's mirror world worth the risk.

George Church: That's a big topic. It's a small topic and almost nobody talks about it, but it, I would say it's not worth the risk. In a replicative sense, but there isn't much risk if we talk about making mirror proteins without replication that very predictably will do reactions.

It's 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 [00:38:00] forth but you can do that with mirror enzymes. And also their ability to persist in, in, in human systems and ecological systems without 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. Almost every engineering discipline has safety engineering is one of its things, like the UL is the safety for electricity and the, you have certification for people to build bridges and buildings and so forth.

So I think we need this is one of those fields.

Daniel Goodwin: 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. So I want to explore this for a second. What is one line of advice you find yourself giving a lot?

George Church: Having to do with curiosity.

Daniel Goodwin: For, or, just in general, as you, as a mentor [00:39:00] for the people that get to work directly with you, is there a theme in the advice and feedback you give people to work for you?

George Church: There are a few. I think that people sometimes penny wise and pound foolish. Most of these things are, they're obvious once you state them, is you'll try to, you'll be trying to save a hundred dollars on an experiment when you're holding society back by a trillion dollars or you're, or even

your own time is worth more than that. Things like that. It's easier to come up with these pithy aphorisms when somebody presents you with a problem. Anyway, that's one off the top of my head.

Daniel Goodwin: Got it. 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?

George Church: We mentioned a few already, like inorganic [00:40:00] developmental biology, synthetic behavioral. I think there's a lot to be determined with biomining, 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.

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 a bad, sometimes it's a bad sign. But you know, there's some really Weird things that, that work out, for example Tom Cech was studying Tetrahymena, which is a pretty obscure protists at the time.

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. Yeah. Yes. [00:41:00] Places to look,

Daniel Goodwin: 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.

George Church: right? Sharks don't kill that, don't kill that many people, and, you could probably surf with a prosthetic leg too.

Daniel Goodwin: On that perfect note, I want to say, George, both 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. 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? 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.

George Church: Thank you all and I love what you're doing for society. Keep it up.

Daniel Goodwin: [00:42:00] Awesome. Thank you.

Paul Reginato: Thanks George.

Daniel Goodwin: Thank you so much for tuning into this episode of the climate biotech podcast. We hope this has been educational, inspirational, and fun for you as you navigate your own journey and bring the best of biotech into planetary scale solutions, we'll be back with another one soon.

And in the meantime, stay in touch with homeworld on LinkedIn, Twitter, or blue sky. Links are all in the show notes. Huge thanks to our producer, Dave Clark, and operations lead Paul Himmelstein for making these episodes happen.

Catch you on the next one.