From Lab to Life: Exploring Synthetic Biology with Drew Endy, John Cumbers, and Jennifer Holmgren

Welcome to Bankless, where we explore the frontier of internet money and internet finance. In this 8-episode series, we are exploring some new frontiers. New frontiers in new technologies, all of which are poised to completely revolutionize the world and change everything about the operating system that society is currently running. Synthetic biology is a fascinating field that combines biology, engineering, and computer science to design and construct new biological systems. By manipulating and reprogramming the DNA of living organisms, scientists can create new functions and traits that do not occur naturally. It's like rewriting the instruction manual of life itself, similar to how we write computer code. In this video, you'll hear from three leaders in the synthetic biology industry—Drew Endy, John Cumbers, and Jennifer Holmgren—who will expand our understanding and imagination of this exciting field. Keep an eye out as we roll out the rest of these boundary-pushing episodes! ------ 🚀 Join Ryan & David at Permissionless in September. Bankless Citizens get 30% off. 🚀 https://bankless.cc/GoToPermissionless ------ BANKLESS SPONSOR TOOLS: 🐙KRAKEN | MOST-TRUSTED CRYPTO EXCHANGE https://k.xyz/bankless-pod-q2 🦊METAMASK PORTFOLIO | TRACK & MANAGE YOUR WEB3 EVERYTHING ⁠https://bankless.cc/MetaMask ⚖️ ARBITRUM | SCALING ETHEREUM https://bankless.cc/Arbitrum 🦄UNISWAP | ON-CHAIN MARKETPLACE https://bankless.cc/uniswap 🛞MANTLE | MODULAR LAYER 2 NETWORK https://bankless.cc/Mantle ------ Timestamps 0:00 Intro 0:50 What is Synthetic Biology? 3:35 The Guests 7:45 DREW ENDY 11:00 Biological Building Blocks 14:15 Understanding the Cell 18:30 The Power of Wetware 22:30 Code and DNA 28:00 The Business Model 30:30 The Biological Revolution 37:00 Longevity 39:20 The Landscape of Possibility 51:00 JOHN CUMBERS 54:30 The Synthetic Biology Rabbit Hole 58:30 Fermentation 1:03:15 Scaling the Revolution 1:07:00 Programming Nature 1:11:45 SciFi Infrastructure 1:19:15 A Grand Vision 1:23:00 Hijacking Biology 1:26:30 A Beautiful Future 1:33:45 JENNIFER HOLMGREN 1:36:00 Building a Circular Economy 1:40:00 Lanzatech 1:44:30 The Renewable Ethylene Business 1:48:30 The Fermentation Revolution 1:51:40 Biological Utopia ----- Resources Drew Endy https://twitter.com/DrewEndy?s=20 John Cumbers https://twitter.com/johncumbers?s=20 Jennifer Holmgren https://twitter.com/TodaDogs?s=20 Lanzatech https://lanzatech.com/ Checkerspot https://checkerspot.com/ Biomason https://biomason.com/ Adidas Jacket https://www.tennispro.eu/adidas-melbourne-reversible-jacket-582214.html#description ------ Not financial or tax advice. This channel is strictly educational and is not investment advice or a solicitation to buy or sell any assets or to make any financial decisions. This video is not tax advice. Talk to your accountant. Do your own research. Disclosure. From time-to-time I may add links in this newsletter to products I use. I may receive commission if you make a purchase through one of these links. Additionally, the Bankless writers hold crypto assets. See our investment disclosures here: ⁠https://www.bankless.com/disclosures⁠

Speaker names marked ? are inferred from speaking time and the show’s known hosts — they are not voice-verified.

• 0:04David Hoffman?

  Welcome to Bankless, where we explore the frontier of internet money and internet finance. And today, on this episode of our Zuzalu series, we are exploring some new frontiers, new frontiers and new technologies, all of which are poised to completely revolutionize the world and change everything about the operating system that society is currently running. On this episode, we are exploring the frontier of synthetic biology, or SinBio for short. Understanding synthetic biology is hard. Learning synthetic biology is a little bit like learning crypto. First, it's very confusing, and then you have an aha moment, and then you see things like you've never seen them before, and there's no going back. So I'll do my best to first give you a primer before we enter our conversations with three of the biggest leaders in the synthetic biology world, including Drew Endy, the father of

• 0:49David Hoffman?

  modern synthetic biology. So here we go. Synthetic biology combines biology, engineering, and computer science to design and construct new biological systems. With synthetic biology, you can manufacture biological components using biology. So synthetic biology is all about manipulating and reprogramming the DNA of living organisms to create new functions or traits that do not occur naturally, yet are still produced with organic means. We all know DNA as the instruction manual for living things. Simply put, synthetic biology is the act of rewriting DNA so that we can write our own instruction manual, like how

• 1:32David Hoffman?

  we would write our own computer code. DNA is a Turing complete computational platform, so the products that come out of synthetic biology are quite literally limitless. We can do anything. It's just a matter of how do we get the biological components to actually ingest the new DNA that we write like computer code. There are simple and down-to-earth applications of synthetic biology, such as engineering bacteria to produce medicines more efficiently. We can modify crops to make them more resistant to pests or drought. But the real reason why synthetic biology gets so crazy is that it is a brand-new computational and manufacturing platform in which its limits start to quickly approach our own imaginations. Biology is a general-purpose technology, and synthetic biology unlocks an entirely new

• 2:17David Hoffman?

  frontier of technological production that we've never had before. So Bankless Nation, take a moment to look around you. Do you see all the material goods that you have? I have a desk here. There are some lights behind me. I drove in a car today. These are all physical materials that are produced in some factory and will all ultimately decay to reach the end of its lifespan and re-enter the outside world, possibly, perhaps, most likely through a landfill. With synthetic biology, instead of having a laborious, resource-intensive manufacturing process, much of the material goods that we use and consume on a frequent basis can be grown, not manufactured.

• 2:58David Hoffman?

  With synthetic biology, the dichotomy between human-produced material goods and nature-grown organic material really starts to blur. And our extremely inefficient analog methods of manufacturing can be replaced by systems that are hundreds of times more efficient and 99% less resource-intensive. So if you believe in the future of synthetic biology, we will be able to grow new cities and everything inside of them. While there are immense challenges and obstacles to getting to this point, the magnitude of abundance that is unlocked has attracted the efforts of some of the brightest minds on this planet, some of which you're going to hear from right now. Bankless Nation, I would love to introduce you to the three leaders that you're going to hear from the synthetic biology world, starting with Drew Endy, the father of modern

• 3:42David Hoffman?

  synthetic biology, followed by John Cumbers, founder and CEO of Sin Bio Beta, and finish up by Jennifer Holmgren, the CEO of Lonza Tech. Drew Endy is going to continue this introduction into the broad landscape of synthetic biology and will continue to open up your imaginations about that world that could be if only we had synthetic biology. We'll talk about the emergence of wetware, as in hardware, software, and now wetware. We'll talk about the read and write functions for DNA and progress towards the programmability of cells. And then we'll zoom out and get into the world in which we can grow buildings, planes, cars, and if Drew Endy is correct, this is all happening in our lifetimes, if you're on the younger side. Then we'll get to hear from John Cumbers,

• 4:28David Hoffman?

  who will continue the conversation after Drew, and give us more specifics about the technical details, about how this all works, how everything starts with fermentation, why nature from first principles is massively more efficient than anything we can manufacture with our own hands, or even with robot hands, and how we actually get to the point of programming multicellular organisms. And then lastly, we're going to hear from Jennifer Holmgren, the CEO of Lonzatech, which is perhaps the largest in-production efforts of synthetic biology. Lonzatech is a company that depends on an additional facility to a carbon emission source, like a steel mill or a landfill. And Lonzatech captures the emitted carbon, and using fermentation, that pollution is converted by bacteria into very simple, composable chemical Legos

• 5:13David Hoffman?

  that can be produced into almost anything. During Jennifer's presentation at Zuzalu, she pulled out three Adidas jackets that were made in partnership with Adidas that had all been manufactured using emitted carbon emissions coming from like a steel mill or some sort of carbon emission source. And so they captured the carbon, and they turned it into a jacket, three of them. One of them was given to Vitalik. It was a black and white jacket. And when Jennifer gave it to Vitalik, he immediately put it on, because everyone was watching. But then Vitalik saw that it was actually reversible, and instead of having black and white on the outside, you could have this purply, rainbowy, pink color. And like, I was watching Vitalik do this, and I realized that he didn't know that it was reversible,

• 5:58David Hoffman?

  because knowing Vitalik, he would immediately put on the colorful side. And like, I saw his face like, light up as soon as he saw that he could make it like, pink and purple and light. It was a very, very classic Vitalik moment. Anyways, small, small little snapshot of life at Zuzalu. So let's go ahead and hear from our leaders of the synthetic biology world, starting with Drew Endy, the father of modern biology. But first, before we get there, a moment to talk about these fantastic sponsors that make this show possible. Kraken Pro has easily become the best crypto trading platform in the industry. The place I use to check the charts and the crypto prices, even when I'm not looking to place a trade. On Kraken Pro, you'll have access to advanced charting tools, real-time market data, and lightning-fast trade execution, all inside their spiffy new modular interface. Kraken's new customizable modular layout lets you tailor

• 6:42David Hoffman?

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• 7:25David Hoffman?

  You can buy, swap, bridge, and stake your crypto assets. So not only is Metamask the easiest place to see your wallets in aggregate, but it's also a powerful battle station for all of your DeFi moves. So go check out your Metamask portfolio, because it's waiting for you to open it up. Check it out at portfolio.metamask.io. Bankless Nation, we are here at Zuzalu, and I'm talking to Drew Endy, who I've been told is the father of modern synthetic biology. Is that, do you accept this title? Is that right?

• 7:53Speaker 01

  When something gets going, there's many parents, so I could be one of. You know, and some of the things that are happening with stem cells, by the way, you can have interesting parentage these days.

• 8:05David Hoffman?

  Sure, sure. So we're going to try and go down the synthetic biology rabbit hole, which is a domain of knowledge which I did not know how incredibly expansive and revolutionary it can be. And I think the listener base will know how optimistic I am about the world of crypto, and now I am slowly getting pilled by the world of synthetic biology, if you will. So Drew, I mean, I'm sure you've explained synthetic biology to 10,000 people at 10,000 different times. How do you, how do you explain it in the fewest number of words possible?

• 8:37Speaker 01

  So get rid of one word right away. Get rid of biology.

• 8:40David Hoffman?

  Okay.

• 8:41Speaker 01

  Focus on synthesis. And go back in time and let's use the Greek version. Synthesis with a U. What does that mean? It means composition or a putting together. So synthesis is about putting things together. When we put that word in front of biology, you get synthetic biology, which is putting biology together. At a fundamental level, it involves research to improve our ability to compose living systems. Does that make sense as a start?

• 9:10David Hoffman?

  Yeah, I'm following, yeah.

• 9:11Speaker 01

  Yeah. So a lot of times when people encounter biotechnology, it's very much as an emerging technology, a doorstep of last resort. You know, like you have a horrible disease. You can't cure it by going to the hardware store and buying nuts and bolts. You know, you can't cure it with AI yet, right? And so it's like, well, maybe we could cure it with biotechnology. And so normally when people think about biotechnology, it's like, what can you use it for right now? The medicine, the food, the fuel, the shelter. And what that's led to over the last 50 years is genetic engineering and a bioeconomy, which we could talk about. But just to come back to it, what's been missing is lower level work

• 9:56Speaker 01

  to make it easier to engineer biology, to put biology together. And so synthetic biology, starting 20 years ago, is really throwing some elbows in the cultural, political space to say, hey, wait a minute. We've got to develop a more solid foundation for working with living systems to solve problems. And to do that work, we have to take a big step back from the application layer and just get down underneath and say, how do we compose living systems? And so that's what's been going on. And then because of that, it's becoming easier to compose living systems. And so if you're not paying attention to what's underneath the surface, you don't see anything. But then suddenly, all these apps start popping up. It's like, oh, like something's changed, but you don't know what it is.

• 10:41David Hoffman?

  So it sounds like, to regurgitate some of this back at you, I'm getting ideas of like building blocks, right? And it sounds like we're going very, very deep in the biological stack to be able to kind of produce building blocks that can assemble themselves. And the applications of this seem kind of endless when we go down to the very building blocks of what makes biology. And understanding and going through the learnings of some of these talks, really it sounds like synthetic biology has found a way to use modern day technology, computers, code, perhaps even AI, to actually create the building blocks that we need to compose living systems.

• 11:23David Hoffman?

  In the crypto world, we use this idea of money Legos, as in building blocks of money and finance. And it sounds like what synthetic biology is, is with technology, finding ways to get down to the basement level of what makes a cell a cell and be able to turn that into building blocks that we control. Is this a fair summary?

• 11:42Speaker 01

  Yeah, it's a fair way of representing it, but I wanna give everybody a sense of where the frontier is, right? So we're doing that work, we're about 20 years into it. It's not a done deal, right? So there's been significant progress, which you can quantify, to say, how much better have we got at composing living systems from the inside out, from the molecular to cellular scale? We can come back and talk about some details or examples, but we're not, we're not done, right? So for example, you know, biology is a general purpose technology. Anywhere you are, you could look at what biology is doing, and it's like, well, could I partner with biology to do more of that or something different? Like, think of a leaf on a tree. It's a self-assembling solar panel that recycles itself.

• 12:25Speaker 01

  It's like harvesting photons, fixing carbon. So that's a really interesting technology, right? So we've got this GPT, not chat GPT, but general purpose technology in biology. We're trying to unlock biology as a GPT. The fundamental unit of life is the cell.

• 12:44Speaker 01

  There's no cell on Earth that is operationally understood completely. Alright, so the best understood cells have about twenty to thirty percent of their componentry, absolutely essential for cell viability, and nobody on Earth knows what those components do. And so what that means is if you're trying to build with biology for any purpose, you're encountering this low-level ambiguity, and it means that your workflow is gonna be Edisonian. It's gonna be tinker and test, tinker and test, which is why you see this investment in foundries and bioworks that allow for high-throughput tinker and test. As a long-ago structural engineer, you know, like, I don't like, I prefer design-build-work to design-build-test, design-build-test.

• 13:29Speaker 01

  Like, if I'm gonna build a bridge, like, I'll design it, I'll build it, the bridge's gonna work unless I'm incompetent, right? So, but because we've got this ambiguity in the fundamentals still at the cellular level for all cells on this planet, the job's not done, right, at the root level.

• 13:46David Hoffman?

  Right.

• 13:46Speaker 01

  And so that's where, you know, like, my academic day job with a lab is like pushing the frontier to get to operational mastery of the cell. And then, which, by the way, I think we'll get to in of order a thousand days, like, it's a this decade sort of thing, then we begin to see an even more interesting domain of biotech.

• 14:07David Hoffman?

  I think where these worlds that, where these two worlds collide, biology and computers, and I think our listener base is pretty intimately aware with how computers work, where they collide, and what you're saying is that cells are decently like computers, except we are missing like thirty percent of the motherboard. We don't know thirty percent of the components that make these things work, and that is the obstacle that the world of synthetic biology is currently facing.

• 14:35Speaker 01

  Yeah.

• 14:36David Hoffman?

  But can you just unpack the metaphor of like a cell as a motherboard or a cell as a computer and how that relates?

• 14:41Speaker 01

  I prefer the metaphor of a cell as a cell.

• 14:44David Hoffman?

  Cells as a cell.

• 14:44Speaker 01

  Cells as a cell, like, metaphors are wonderful and they're dangerous.

• 14:49David Hoffman?

  Sure.

• 14:50Speaker 01

  So, so, like, something to think about is...

• 14:54Speaker 01

  You know, computing is operating primarily at the intersection of joules, J O U L E S, and bits. And it uses hardware to render that interface. Living system cells are operating in the domain of joules, bits, and atoms. Right? Like, life's harvesting energy from a source. We've got bits in the genome, and then we've got the self-mixing milieu comprising the cell. So, so, hmm. And so I think of it as wetware. You know, like, there's hardware, there's software, there's wetware. And, and so a cell is a cell. Like, let's use the metaphor, like, let's just, let's just let a cell be a cell. And, but we can, we should talk about it more specifically.

• 15:34Speaker 01

  So, for example, let's say I took a bacterium that's microscopic, one millionth of a meter long, a micron, and I'm just gonna have a magic wand, I'm gonna make it a hundred million times bigger. So now it's a hundred meters long. And I'm not adding more atoms, I'm just, like, magically making everything bigger. So we can see it. It's like the size of a building.

• 15:54David Hoffman?

  Okay.

• 15:55Speaker 01

  All right? Now, now, we can say, well, what does it look like? Let's say I've got a protein, a green fluorescent protein that makes a green light. Right? That protein is the size of a basketball. All right? And, and then the ribosome, which is a collection of molecules that makes proteins, is two meters tall. Right? And then the genome, the DNA, it's going back and forth in this building 1,600 times. Right? It's really thin thread, and so its cross-sectional area is like four square meters. All right? And, and then there's many other molecules in this building, all about basketball size, and they fill 30% of the space of the building.

• 16:40Speaker 01

  Right? So it's 30%, we call that volume fraction. It's 30% packed with molecules. And, and this is just like, now we're just building this instantaneous mental image of what a cell is. And, and, of course, it's alive. And, and what that means is it's self-mixing. You know, like, Brownian energy is causing all the molecules to jostle around through collisions with water. So that soccer ball, that green fluorescent protein is moving with an average, this is where it gets crazy, is moving with an average velocity of 500 meters a second. Its instantaneous velocity is faster, probably. It's like, alright. So what that means is the molecular molecular collision time is a nanosecond.

• 17:24Speaker 01

  So I've got this self mixing milieu that's 30% solid, 70% water with a gigahertz collision rate. And what it's doing is it's being encoded by the genome, instantiated as a physical mixture. It's receiving energy from the environment and within a period of 10 to 20 minutes, it can make a physical copy of itself, right? So it's like, that's wetware, right? And I know it's like a lot to think about.

• 17:55David Hoffman?

  Right.

• 17:55Speaker 01

  And I like making it macroscopic. By the way, I would love for somebody to

• 17:59David Hoffman?

  Turn that into a visual?

• 18:00Speaker 01

  Turn that into Minecraft.

• 18:02David Hoffman?

  Right.

• 18:03Speaker 01

  Like build a cell on Minecraft, right? And like, let's like have empathy for it there. But I love metaphor. I fall into the rabbit hole of metaphor all the time. But like, we've just got to get to wetware on our own terms. So like, that's what I really want to just, yeah, get for that.

• 18:20David Hoffman?

  And I think the motivation behind why you presented that illustration is to really put the idea of the power of wetware

• 18:29Speaker 01

  Yeah.

• 18:30David Hoffman?

  that we just do not have in our current technological landscape as it relates to like computers and chips and engineering. Like wetware biology, the promise of synthetic biology is that the wetware can become the orders of magnitude more powerful than what we have today.

• 18:49Speaker 01

  There's two things that are going on. One should be apparent already and then there's something that synthetic biology uniquely unlocks. So the one that everybody can see, hopefully already, or begin to imagine from what we're talking about, is I've got an object that can grow a copy of itself. Right? Like, my phone does not

• 19:09Speaker 01

  Organize matter from the environment and grow off and bud another phone. Right? So biology begets biology, right? We've got reproducing machines in a Johnny von Neumann sense.

• 19:20David Hoffman?

  Right.

• 19:20Speaker 01

  But it's like the wetware is a self reproducing machine. Right? So that's where there's profound power. The other thing that's happening is the technologies of synthetic biology include things like reading DNA or DNA sequencing and writing DNA or DNA synthesis. All right, so so let's just dive into that for a second.

• 19:44David Hoffman?

  Please.

• 19:44Speaker 01

  Okay, when I sequence DNA, I have a physical copy of DNA, the atoms. And then I read it out and I turn it into a representation which I can ATCG and so on. Right? And so that that can be represented itself in zeros and ones. So sequencing of DNA lets me goes from atoms of a piece of DNA to bits. All right.

• 20:04David Hoffman?

  And that's the translation and how that that link allows us to do things as humans. That's how we manipulate.

• 20:11Speaker 01

  We can move a representation of the genetic code onto the network, onto a computer. We can compute upon it. All right. And so that we can learn about it.

• 20:19David Hoffman?

  Right.

• 20:19Speaker 01

  Right? And then we can redesign it in the bit layer. How do we get back to atoms? Well, it's DNA print synthesis. Right? And so DNA synthesis is a tool that lets us specify a sequence and then dispense chemicals in a particular order to reconstruct a polymer of DNA encoding whatever we specify. Right? So it's like TA, TA, CG, ACC, C, ACT, TA, G, G, G, GA. Like, what's that? Oh, that's a promoter that turns on gene expression. By the way, you can memorize sequences by making them your login passwords. Right? So like, that's a real sequence. It's a functional sequence that gets genes expressed. But but like zoom out for a second.

• 21:00Speaker 01

  Atoms to bits with reading, bits to atoms with synthesis. So those two technologies, DNA sequencing and DNA synthesis, make genetic material and genetic information interconvertible.

• 21:13David Hoffman?

  Right.

• 21:13Speaker 01

  And let us take the superpower of the internet, which is to move information around in spacetime by decoupling and recoupling it, and combine it with the superpower of biology, one of which is growth and reproduction, but the other is biology grows with the materials that are where the biology is. You know, the leaves on a tree don't come from a factory in Detroit and are shipped on pallets and then taped and stapled to the twigs and branches, like, uh-uh. The photons arrive, the nitrogen arrives, the water arrives, the carbon. Where the biology is, so like, all atoms are local, is another secret superpower of biology. So it's the ultimate distributed manufacturing platform. So what happens, so this all of a sudden now synthetic biology, rabbit hole, I, hopefully you're seeing is like crazy interesting.

• 21:56David Hoffman?

  Right.

• 21:56Speaker 01

  We're gonna take the superpower of the internet, decoupling information from spacetime, and then we're gonna connect that bio-information with all the power of compute, but then we enable biology's superpower of growth and reproduction and local manufacturing, right? And so now we've got a bionet we can foresee, if we wanted to push the limits of deglobalization, we can go for that, and so on and so forth.

• 22:23David Hoffman?

  I, I, I hope what listeners are starting to see is like, first we have this read and write layer, which is what you talked about. First we can read DNA, and that was a technology that we unlocked a number of decades ago. Then we upload that information in byte code, in, in, in bytes, in, in binary.

• 22:38Speaker 01

  Yeah.

• 22:39David Hoffman?

  And we have that expressed in digital form.

• 22:41Speaker 01

  Yeah.

• 22:41David Hoffman?

  And this is when other technologies, AI, the internet, open source, can start to influence those technologies. And then we can start to write DNA.

• 22:50Speaker 01

  Yeah.

• 22:50David Hoffman?

  And then we have another technology that actually likes that write DNA to actually manifest in actual DNA creation.

• 22:56Speaker 01

  That's right.

• 22:57David Hoffman?

  And then this is, what's the next, and so that's the, the read and write stack of this layer.

• 23:01Speaker 01

  Yeah.

• 23:01David Hoffman?

  What's the next, what's the next higher order stack? What happens next?

• 23:04Speaker 01

  Yeah. I want to backfill something, just in case it helps people ponder. A lot of people know about 3D printers, right? Think of a DNA printer as a 1D printer. All right, it's making a polymer of DNA, it's a line. Yeah. It's a 1D printer, right? However, that 1D printer programs the molecular machinery of cells, including ribosomes, that get you to three dimensions, right? So I've got a 1D printer that programs, actually, three and four dimensional with time, you know, manufacturing platform, right? So it's kind of interesting, we've got a 1D printer hidden in DNA synthesis. The next level up is cells and ecosystems.

• 23:47Speaker 01

  And, you know, what's beyond that is microscopic and macroscopic manufacturing. You know, so what can you do with a cell, right? And the answer is anything biology can do. My wife's work, for example, is to reprogram yeast, Saccharomyces. By the way, it's like, these words might sound strange, but it's like, right in the word is oftentimes a description of what it is. Sugar-loving fungus. Saccharomyces, and then Saravisiae, beer. Like, sugar-loving fungus beer, right? So that's brewer's yeast, right? So normally, you'd take, that's a cell, you know, it's a reproducing wetware machine, right? It's like four to eight microns in diameter.

• 24:30Speaker 01

  Normally, it would take in glucose, and it would make ethanol and carbon dioxide. All right, and some other things.

• 24:38Speaker 01

  You know, her team can reprogram the metabolism of yeast to take in glucose and make scopolamine, or morphine, right? Chemicals that would normally be found in plants.

• 24:51Speaker 01

  By the way, you know what's really cool about plants? Tell me. They don't have feet. They don't have legs. They can't run away.

• 24:59David Hoffman?

  Oh.

• 25:00Speaker 01

  It's like so crazy. Like, when you stop and think about it, like, imagine being a creature that's a rooted creature that you can't run away from stuff. Like, what would that be like? And how would you protect yourself? And, and so, because plants can't run away from insects or mammals over evolutionary timescales, they've developed defenses and modulators of insects and mammals, which are these crazy chemicals we find in plants.

• 25:25David Hoffman?

  Right, and so what you're saying there is that they have been rid of the opportunity of running away. So, in, as a reaction of that, they have instead created a explosion of other compounds and proteins that we can now upload and learn from, and those are our building blocks now.

• 25:41Speaker 01

  Well, an inspiration of chemistry, basically, like, a whole molecular keyboard, right, that can, that can be, like, used to pro, like, you, you know, you ingest certain plant substances, they change how you feel and your behavior. Caffeine, you know, but many others. But, but so, we can take inspiration from the chemicals found in plants, but how would we get those chemicals? Traditionally, we'd grow the plants.

• 26:05David Hoffman?

  Right.

• 26:07Speaker 01

  Do you know where morphine comes from?

• 26:10David Hoffman?

  Once upon a time, I did, but no longer.

• 26:13Speaker 01

  Poppies.

• 26:13David Hoffman?

  Right, yes, yes, yeah.

• 26:15Speaker 01

  Opium poppies, right. So, of course, there's an illegal market for poppies. But, you know, like, if you need a pain medicine, it's very, you know, properly, you know, derived and supplied. Like, how does that get to you? What, what does it start with? And the answer is, we have legal poppy fields in certain places. There's not too many places where you can grow poppies due to climate. One place is Tasmania, right? And so, we'll have poppy farming in Tasmania. The poppies will be harvested after a period of time, a year or so. Then you have to extract the active ingredient out of the plant and then move that around the world under careful scrutiny and regulation, and then formulate that into a medicine, right?

• 26:58Speaker 01

  So what if instead of all that, you could, you know, reprogram the metabolism of yeast to take in sugar and make morphine? Or take in sugar, make scopolamine. Scopolamine is what's in the motion sickness patches, right? Or take in sugar and make any plant natural product found on Earth. And you didn't have to do that in Tasmania. You could do it in Minnesota, or Montenegro, or Indonesia, or Micronesia, or pick your place. Right? And so now-

• 27:23David Hoffman?

  And importantly, not with poppies anymore.

• 27:25Speaker 01

  That's right, with yeast, with Saccharomyces, the sugar-loving fungus. It's no longer Sarah Visier, it's Medicine of Visier or something, right? And so, and so, you know, the neck to your question, you know, once you get up, up, up, up above the molecule scale, you get to the cell scale, and what synthetic biology unlocks is routinization of programming cells. And I just want to be careful again. We have not yet made routine, the programming of cells, but we've made significant progress towards it, and we can see the light at the end of the tunnel. And it's not a train coming at us. It's like, oh, we're, we're this decade unlocking biology as a general-purpose technology.

• 28:01David Hoffman?

  I think the, the main point, I think, Les Travers should really put emphasis on is that, okay, so if we want to make morphine, we don't need a poppy field. If we want to make X, we don't need to harvest the environment. We can create this at scale in a lab without, and the only thing we need is we need to encode the DNA of the molecule that we want to produce. Is this correct?

• 28:24Speaker 01

  That's right, we need the biocode that can instantiate the process.

• 28:27David Hoffman?

  Right, and then once we have the code, then we have the scale.

• 28:30Speaker 01

  Right. Couple other things. The go-to-market reality around all these technologies right now is framed within a context of, talk about metaphor, industrialization. Both metaphor and practice. Now, what does that mean? Concentrated capital, concentrated manufacturing. If you want to create a synthetic biology company today, you're gonna get 10, 100 megabucks and build a team. And so instantly, right there, you're accessing centralized capital traditionally. And then the biology you're making's gonna go into an industrial fermenter somewhere to supply the industrial economies with a drop-in replacement supply chain for the same stuff. Right, so that's, it's kind of boring. And then it also has an obvious deficit going forward,

• 29:13Speaker 01

  which is the industrial supply chain's only provision on this planet for 2 billion people, more or less. Right, so if you actually cared about getting essential medicines to 8 billion people, you know, that's not gonna get it done. However, in what we're talking about already, like, how many people can run a fermentation?

• 29:30David Hoffman?

  Right.

• 29:30Speaker 01

  Everybody.

• 29:31David Hoffman?

  Right.

• 29:31Speaker 01

  You know, you could be in a rural hut in India with a fermented breakfast bread, idli, I D L I. And within that context, you know, if you needed to brew a medicine, you should be able to enable the brewing of medicines. The issue right now is that person might not have very much money. So, you know, we're not going to supply them through Amazon Prime or whatever, like what they need. So synthetic biology, as it's maturing this decade, is is gonna have to confront like this transition to flourishing and abundance, which is like, how do we get beyond the metaphor and practice of industrialization? And bring to, you know, a lot of people talk about industrializing biology. I like flipping that around. Like, I like biologizing things. So what does it mean? I don't want the fourth or fifth industrial revolution.

• 30:16Speaker 01

  Like, that's horrifying.

• 30:18David Hoffman?

  Right.

• 30:18Speaker 01

  Right, I want like something different. I want biologizing.

• 30:21David Hoffman?

  You want the first biological revolution?

• 30:22Speaker 01

  That's right. That's right.

• 30:23David Hoffman?

  Yeah, maybe you could just help us imagine what that actually means. What does a biological revolution look to you?

• 30:30Speaker 01

  Yeah, okay. So, Bayer before the year 2050, we can enable 10 billion Homo sapiens to flourish on this planet in partnership with everything else on here. Right? So, so that's the opposite of what I've been experiencing for the first 50 years of my life. The human population has doubled over my lifetime, and the natural biodiversity indices have been cut in half. Is that correlation? Definitely. Is it causation? For sure. Right? Changes in land use, pollution, introduction of invasive species. So, so at a planetary scale, what I'd like to deliver is, working together with as many people as possible, is a functioning planet that's got 10 billion Homo sapiens flourishing along with everything else.

• 31:13Speaker 01

  It, and I don't mean this as, by day, I'm an academic. By night, I mean, we're getting this done. Right, like Bayer before 2050. And it looks to me like, for the first time in human history, we can pull it off. You know, not in some wishful thinking, like, no, they're gonna do it, like Bayer before 2050. So what biology represents is the intersection of joules, bits and atoms. Everybody listening and we are operating on energy about 100 watts. We need to be instantiated via atoms. We have knowledge and information. So at the lowest root level of what it means to operate and exist, it's like joules, bits and atoms. And so how do we unlock that? And because biology is right there at that intersection, it's a critical tech,

• 31:54Speaker 01

  right, to get to flourishing. So let's just talk about numbers for a second. Primary driver of biomanufacturing from an energy perspective is obviously photosynthesis. There's 90 terawatts on average at any moment in time of photosynthesis on the earth.

• 32:11David Hoffman?

  Sun landing on the ground.

• 32:12Speaker 01

  No, sun, not landing on the ground, being, the photons being harvested by chlorophyll to fix carbon.

• 32:20David Hoffman?

  Sun landing on plants that's being utilized by plants.

• 32:23Speaker 01

  It's like 90 terawatts. Think about it like solar panels, right? But it's like photosynthesis. How much energy is being harvested by leaves? It's like of order 90 terawatts, 70 on the land, 20 in the ocean. Civilization's running on 20 terawatts, to keep it simple. So 90 is four and a half times 20. Just the napkin math right there, just like, hmm. We have enough juice powering manufacturing via biological growth that's like four and a half times what civilization's consuming. Like, right there, it should feel pretty good. Like, should be enough. You know, it's not like, it'd be better if it was a thousand times more. But like, that feels pretty good. Here's where it gets even better.

• 33:06Speaker 01

  I heard, maybe you know, I mean, I heard that on this planet, the Homo sapiens tribe did a terawatt of photovoltaic panel manufacturing last year. Did you hear that?

• 33:18David Hoffman?

  No.

• 33:19Speaker 01

  I heard that, yeah. At Stanford, we've installed a million solar panels. That offsets the entire campus electricity load.

• 33:29Speaker 01

  I've heard that, you know, the return on energy for a solar panel went above one sometime in the last decade. A lot of people think of ROI, like, how much does a panel cost? How much is the electricity worth? And when do I get my money back?

• 33:42David Hoffman?

  Right.

• 33:42Speaker 01

  Right? I'm a nerd, so like, I like return on energy.

• 33:45David Hoffman?

  Right.

• 33:45Speaker 01

  How many joules, J O U L E S, does it take to make the panel? And how many joules does the panel get? When do I get my energy back? What's my ROE?

• 33:53David Hoffman?

  Right.

• 33:53Speaker 01

  So apparently, in the last decade, ROE for solar as a sector went above one. And now it's, now it's averaging 20 to one.

• 34:00David Hoffman?

  Oh, great.

• 34:01Speaker 01

  So that means in Menlo Park, I'm getting my energy back in a year.

• 34:04David Hoffman?

  Mm-hmm.

• 34:05Speaker 01

  Oh, that means we're transitioning to electricity generation abundance.

• 34:09David Hoffman?

  Mm-hmm.

• 34:09Speaker 01

  Right? And if I'm doing a terawatt of panel manufacturing this year, you know, like, how many years until I get to 20? Or 20, obviously, right? But then it's interesting, everything else being equal, and who knows where it goes off the rails, we're increasing panel manufacturing. You know, it looks like we're gonna run out of silver and other things with current tech, but, but we can get a couple more doublings. So my prediction would be if that trend continues, sometime in the 2030s, we're actually electricity generation abundant. What's that have to do with synthetic biology? Wait for this. So, like, a lot of times you think about electricity generation, but you gotta transmit it, and you gotta store it in batteries. That's fine, that's valid. But, but let's bring it to biology.

• 34:50Speaker 01

  So you can take electricity, and you can split water, and you can use that to fix carbon from the atmosphere.

• 34:56David Hoffman?

  Mm-hmm.

• 34:57Speaker 01

  And you can make simple, single, single-carbon organic molecules, like formate, F O R M A T E. You can make other things, but like, formate's an easy one. And so, a kilowatt hour of electricity might get you a gram of formate. Well, remember those organisms that normally eat sugar? We can bioengineer them to eat formate.

• 35:15David Hoffman?

  Mm-hmm.

• 35:16Speaker 01

  All right, so now I go, electricity, however sourced, to fix carbon formate, and now formate to biomass, a medicine, or whatever biology grows. And when you talk to the material scientists and chemical engineers, they think they can improve the front end to kilowatt hour of electricity to 30 grams.

• 35:34David Hoffman?

  Mm-hmm.

• 35:35Speaker 01

  30 grams of formate. I don't know this is going to pull a lot of carbon out, but what it means practically for me is I can lift the ceiling on how much biology can grow by electricity generation. And more importantly, you know, I can only do farming in places where I've got good soil or an enclosed shipping container and like hydroponics and reasonable water supply. But I can do electrobiosynthesis anywhere I can put a panel.

• 36:01David Hoffman?

  Right.

• 36:01Speaker 01

  Because I'm going to have carbon in the air and I'm going to have other things I need that I can source locally. And so, and so, hmm, like, I'm just feeling like I got line of sight to abundant joules and I can connect that to biology directly. And now I can do not only agriculture, I'm not against agriculture, that's amazing, but now I can do electrobiosynthesis in various places locally, right, to get even more biological manufacturing. And so it looks to me like we've got a line of sight to solving the joules puzzle and the atoms puzzle. And so then the only thing that remains is how are we operating our knowledge networks?

• 36:38David Hoffman?

  Mm hmm.

• 36:38Speaker 01

  Right? It's like, we've got a pretty good platform for that already.

• 36:41David Hoffman?

  And so when you say you see line of sight, what I'm hearing is that everything seems to be a known quantity. To get to the point of the only constraint is our imagination and the data that we can get from DNA and the building blocks that we know how to build.

• 36:57Speaker 01

  Well, and we've got to complete the fundamental engineering work.

• 37:00David Hoffman?

  Right.

• 37:01Speaker 01

  To unlock biology as a GPT. So like, let me, let me come back to metaphor.

• 37:06David Hoffman?

  Sure.

• 37:06Speaker 01

  In a, in a, hopefully not too risky way.

• 37:08David Hoffman?

  Right.

• 37:10Speaker 01

  Do you care about longevity?

• 37:11David Hoffman?

  Yeah.

• 37:12Speaker 01

  All right. So, so let's talk about longevity in the context of a Linux server.

• 37:20David Hoffman?

  Uh huh.

• 37:20Speaker 01

  All right, so we're going to talk about server uptime. That's like server longevity.

• 37:24David Hoffman?

  Mm hmm.

• 37:24Speaker 01

  Right? And like Linux is pretty stable now. And so like remarkably, you know, high uptime, like long, long live server uptime.

• 37:35Speaker 01

  Imagine if you didn't understand thirty percent of how Linux or Unix worked. And it wasn't just you, nobody on earth understood that. And there was some memory leak or some other thing. And you're like, like inevitably you'd have to reboot.

• 37:51David Hoffman?

  Right.

• 37:52Speaker 01

  Right, so like you could go work on on server uptime or longevity. And no doubt you'd like hack together some things that would like, oh, the uptime's gone up by a factor of two.

• 38:02David Hoffman?

  Right.

• 38:03Speaker 01

  Right, and like everybody, yes. You're like, we're living twice as long, our servers are living twice as long. Be a practical advance, be a big deal. But you really wouldn't crack the puzzle. Right, because like unless it was like total dumb luck and you probably never get there. Or let's say you cared about security of your servers. Right, you need to secure your server and you don't understand thirty percent of how the operating system works. And nobody on earth does.

• 38:28David Hoffman?

  Right.

• 38:28Speaker 01

  Right, like, but but the things you don't understand are each little thing that you don't understand is absolutely essential for server operation.

• 38:35David Hoffman?

  Right.

• 38:35Speaker 01

  Like if anything that you don't understand goes wrong, the entire server crashes. Secure your server. Right, like, okay, you're gonna air gap it and pray.

• 38:44David Hoffman?

  Right.

• 38:44Speaker 01

  Right, like, that's it. So, so, so the, the, I wanna, it's like what we're confronting in synthetic biology is massive cultural challenge to represent and communicate that we've got this low level ambiguity, you know, at the bottom of the stack, at the cell. And until we can overcome that.

• 39:03David Hoffman?

  Right.

• 39:03Speaker 01

  No matter what you care about, provisioning medicines or living longer or biosecurity, it's like, good luck. You're gonna be on your heels reacting and hoping and praying. So, so like, we've got to get that part done, right?

• 39:17David Hoffman?

  Okay, so, so this is the, the, the current frontier of knowledge that we are at with synthetic biology. And so I want to assume that we solve that problem. Because I believe in human ingenuity. And I want to kind of like move forward into the, into twenty forty, twenty fifty, where we start to really leverage the best of this technology. Some of the metaphors that we were talking about. And when we're having this in Sin Bio, uh, block meets blockchain, uh, weekend this weekend.

• 39:45Speaker 01

  I found a piece of the blockchain.

• 39:47David Hoffman?

  Yeah, that's it. That's listeners or watchers. That's why that's this block is here.

• 39:50Speaker 01

  I found this on the beach. It's the only part of the blockchain, I understand. Like fell off, fell off the blockchain.

• 39:56David Hoffman?

  Well, so I, I wanted, so a lot of like very big sci-fi ideas got presented in this, this last week. And we talked about like growing buildings. Or there was this demo video that's where we had a, what was it a helicopter? But it's actually a bee and we got this guy is like driving a bee around, except it's a mechanical bee and we grew it. Can just, I know we're, we're running out of time because I believe you have to catch a flight to, to get out of here. Maybe you can just like leave the listeners and myself with some imagination about like when we really master this technology.

• 40:28Speaker 01

  Yeah.

• 40:29David Hoffman?

  What does the world look like? What, what can we do? What can we really do with it?

• 40:33Speaker 01

  Well, let me just give you a sense of staging.

• 40:35David Hoffman?

  Sure.

• 40:36Speaker 01

  Right. So I think the remainder of the 2020s is developing and proving out the fundamental tools. To unlock biology as a GPT. And then the decade of the 2030s is seeing those deployed wherever they need to be. And then the 2040s is filling into flourishing. And we could accelerate that, but it's like, that's a lot to do, right? And, and like, it's like develop, deploy, do is how I'm thinking about the timing of it. And it, it won't be segregated so cleanly, but you get the idea. There was a, have you seen the Lithuanian synthetic biology movie called Vesper? I think it's on Amazon streaming for like five bucks. It's a dark movie. It's not a wonderful future.

• 41:18David Hoffman?

  Synthetic biology dystopia?

• 41:21Speaker 01

  Well, I mean, there's a heroic.

• 41:22David Hoffman?

  Sure.

• 41:23Speaker 01

  Protagonist. She's amazing. Um, and there's hope at the end, but it's like a dark setting.

• 41:27David Hoffman?

  Sure.

• 41:28Speaker 01

  But I, I want to give credit to the world builders and others who conceptualized. What it's like when we have biotechnology. We think of biotechnology like hidden away in a fermenter. Right. Or it's something that's in the. But like, like, like, you know, I talk with my kids about like the purple booger project. Right. It's like, I've got a commensal microorganism that doesn't make me sick. It lives up in my sinuses and it's always doing embedded surveillance about what's infecting me. And if nothing's infecting me, my mucus is its normal color. But I've got an influenza strain in there, suddenly my mucus is bright orange. If I've got a coronavirus strain in there, my mucus becomes bright purple. Like, why do I have to go somewhere else and send my biology somewhere else? Like in plastic stuff to get like, no, no, no.

• 42:13Speaker 01

  Like, I should just be able to use my biology to tell me what I'm doing. So, so it's like biology that's embedded within us, on us and within our environment. The Vesper team did this really nice exploration into world building. And I prefer that over the wonderful like Formula One B helicopter thing. Like, that's very. You know, the artist Phil Ross really pioneered microtexture. Building buildings using mushrooms. All right. So, so I had a dream, I was, when I was back at MIT, I went to the, um, used to go to lunch in the architecture department up on the fourth floor. There's crazy poster one day, Fab Treehab. And some architect had done speculative design about this living treehouse.

• 42:56Speaker 01

  It was like a four bedroom, two bath. Like, yes, like, I'm gonna make that. Right. And I didn't know how to do it. And so when I was moving to Stanford, that's near Half Moon Bay. And we've got the giant pumpkin competition. And I'm like, okay, like thousand pound pumpkin, that's like almost as big as like a trailer. Right. So I'm like, I'm gonna have to figure out how to make giant programmable gourds that grow and differentiate into a four bedroom, two bath. And that's how I'm getting my. Now, here's where it gets better. If you walk around the main quad at Stanford, you can find hidden on the pavers, the only corporate advertising on our buildings. It says, and it's hidden away, like George Goodman's Artificial Stone, 1890.

• 43:35Speaker 01

  What's this? And now Mr. Goodman was San Francisco's best purveyor of artificial stone. Like, that's reinforced concrete, or concrete. And, and artificial is not a pejorative in the late 19th century. It's like point of pride, brand marketing. Like, oh, we've got the good stuff. It's the artificial stone. Right? And, and, well, what is artificial stone? We grind up natural stone and reform it, synthesize it, compose it, put it together to make stone with the properties we like, when and where we need it, quickly. It's like, ah, what does this mean in terms of like, growing a house? Or, how would I ever grow a mature oak tree in, how long does it take? Like, 72 years? I can't wait that long. I need to make a mature oak tree in 72 hours. Right?

• 44:16Speaker 01

  Only way to do that is like, I gotta grind up trees and then quickly make a new tree. Right? Now, it turns out there's organisms that eat this type of material. It's the wood fungus. Right? And so the artist Phil Ross brought me to this family farm in Monterey called Far West Fungi, which is the local supplier of gourmet mushrooms. And when you go to that farm, it's, it's just hanging out in the strawberry fields, you know, near the Pacific Ocean. They get piles of wood chips for free, approximately. And they mix that up with the organisms that eat wood. But because they're wood chips, they're super surface area. And they very quickly transform that material into a new material. Right? And so you can do mycological manufacturing.

• 45:00Speaker 01

  And Phil was building tea houses out of mushrooms that you can use to make tea. And so you could go to the Museum of Art in San Francisco and step inside his mycological tea house and break off a piece of the tea house and make tea from the tea house and drink the tea in the tea house. Right? And so, and then David Benjamin in, in New York, he's an architect in Columbia, did a pop-up, like, three-story tower, right? At the Museum of Art in New York. And so, and so it's like, yeah, like, biology operates at the nanoscale with atomic precision. And it can grow macroscopic objects. Like, here's a fantasy that's beyond what I could promise, but I can imagine it.

• 45:39David Hoffman?

  Right.

• 45:40Speaker 01

  Inspired by, check out and search online for the living root bridges of India. You can find these double-decker suspension bridges made from rubber tree roots. So like Golden Gate Bridge, right, like here's a Golden Gate Bridge. Super gigantic coastal redwoods. Of course, they need to be reinforced with some type of advanced polymer that we're gonna have to biosynthesize for buckling and stuff like that. And then we're gonna do the main suspension cables with spider thread, right? But instead of making spider thread in a fermenter, I actually wanna have choreographed spiders who are friendly. And they're actually just weaving and maintaining the suspension cables, right? And so like, I don't know how to actually do that, but I can imagine that.

• 46:25Speaker 01

  But I can show you and point you to things like a three-story tower, right? Or a house you could sit in and have tea, you know, working with wood fungus and things like that. What I'm focused on personally is the more boring part. Like, let's just deal with the stuff we gotta get done in the context of who and what we are now and take the Jules, Bits and Adams layer off the table as an issue, like check, right? And if we can get that right, then first, we can say, well, we're not trashing the place, so things aren't going extinct, right? Over and over and over and over again with the increasing pacing, right?

• 47:08Speaker 01

  And then we can get to the more interesting thing. I'll leave you with one last metaphor, right? Because I think it's much more interesting than I can imagine. In the 1960s, there was a space race to get a Homo sapiens up out of the Earth's gravity well, right? So we're familiar with the idea of a well as a metaphor, and we're down in the gravitational field of the Earth, and we're stuck here on the surface. We use a rocket to get up and away, right? We're also in a life well, right? So we're constrained, all life on Earth is constrained by the life that came before, the lineage, and by needing to physically reproduce.

• 47:50Speaker 01

  We come from parents, we beget children, and in a changing world, we have to be able to evolve, right? So there's three profound constraints on all life on Earth: lineage, reproduction, and evolvability.

• 48:04Speaker 01

  When we unlock synthetic biology, we remove all three constraints.

• 48:09Speaker 01

  Getting to a fully understood cell, that work will involve learning to build cells, mixing molecules together. So we won't have constructed, we won't have created life, we'll have constructed it. And that's getting up out of the earth's life well perched on its lip. It's much more interesting than the vacuum of space, because now you can compile back down to anything life could be, which is way more diverse than what could ever be on any one planet, right? And so it's, it's like actually impossible to imagine all the things that could be made.

• 48:39David Hoffman?

  Right. It's impossible to imagine because, like a computer, biology is also Turing complete, so it doesn't have any limitations.

• 48:47Speaker 01

  It's, yes, and it's operating in the realm of atoms.

• 48:49David Hoffman?

  Right. Drew, unfortunately, we have run out of time, but this was a fantastic first start into the, the very, very dense and deep subjects of synthetic biology. I hope to continue this conversation with you and many others in the synthetic biology space here on Bankless.

• 49:02Speaker 01

  Thank you very much. Thanks for connecting. Looking forward to more.

• 49:05David Hoffman?

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• 49:50David Hoffman?

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• 50:34David Hoffman?

  like Game7 for Web3 Gaming and Bybit for TVL and Liquidity and Onramps. So if you want to build on the Mantle network, Mantle is offering a grants program that provides milestone-based funding to promising projects to help expand, secure, and decentralize Mantle. If you want to get started working with the first DAO-led Layer 2 ecosystem, check out Mantle at mantle.xyz and follow them on Twitter at @zeroxmantle. Bankless Nation, we are at Zuzalo and I'm talking with John Cumbers of CIN Bio Beta. And we're going to explore the world of synthetic biology, which, listening to John and listening to him emcee the CIN Bio event that happened last weekend, really blew my mind. And I'm hoping we can convey some of that information here today. John, welcome.

• 51:15Speaker 02

  Awesome. Good to be here, David. Thanks for having me.

• 51:17David Hoffman?

  Yeah, John, you want to give us a little bit about the background of how you fell down the CIN Bio rabbit hole and what you're doing at CIN Bio Beta?

• 51:25Speaker 02

  Sure. The rabbit hole I fell down was the, actually the longevity rabbit hole and the space settlement rabbit hole. So about 20 years ago, I was lying on a bench in Malaysia, where I was an exchange student, looking up at the stars and trying to figure out what I wanted to do with my life. I think I was 21 at the time. And just looking at all these beautiful stars twinkling out there and thinking, there's got to be more to this. There's got to be other civilizations out there, other life forms. And I'm an explorer. I love to travel. I love to explore. So I wanted to go find other life in the universe. And that led me down the longevity rabbit hole, because it was like, well, these are really far away, these other star systems. How are we going to get there? Well, let's figure out how we can live longer,

• 52:09Speaker 02

  how we can put the body into homeostasis. You can travel through time, through the universe. And that got me into biology. At the time, I didn't know how a gene related to a protein. I didn't know what a gene was. I didn't know what a protein was. And so I then went back to the UK, where I'm from. Switched my career from computer science into bioinformatics and then I went on to do a PhD in the USA and then went on to work at NASA for seven years. I started their synthetic biology program. So I fell down and then I started Sin Bio Beta, which is this innovation hub that brings together synthetic biology entrepreneurs and investors. And the biggest thing that we

• 52:49Speaker 02

  do is a conference, which we've done for 11 years in the Bay Area. About 2,000 to 3,000 people come every year and we bring together the whole ecosystem. Everybody who's doing reading, writing and editing of DNA, programming with biology, designing, building and testing of biological systems and circuits to make things with biology. So yeah, that's kind of a 20-year rabbit hole that I went down and just so excited about learning about what you can do with biology and what the potential is.

• 53:19David Hoffman?

  Yeah, and Bankless listeners will of course be familiar with the idea of a rabbit hole. We talk about it all the time in crypto. And one thing I'm very much learning here at Zuzalu is that there are many other rabbit holes out there. And a lot of this is very interdisciplinary. You said that we were here about to talk about synthetic biology, but another big rabbit hole that is here at Zuzalu is longevity. And so I think this has really been the theme of Zuzalu is these interconnections, these rabbit holes are starting to weave together. Now we're finally getting crypto involved, but I'm hoping you can kind of give us the lay of the land for the synthetic biology rabbit hole. Kind of like, show us the map, if you will. Where does this whole thing start? Where is the genesis of the rabbit hole? How do we enter this?

• 54:05Speaker 02

  Yeah, it's a great question. I think we can enter it about 50 years ago when Genentech was founded. And Genentech is a biotech company and the first product of recombinant DNA, that is recombining DNA, was insulin. And if you were a diabetic 50 years ago, your insulin would come from the abattoir.

• 54:32Speaker 02

  Pigs would be slaughtered for food and their pancreases would be extracted and the insulin in their pancreas would be bottled up and sold to people who had diabetes. They have a pancreas that can't produce insulin, so they need to get it from somewhere. They got it from pigs. Now, if you're a diabetic, your insulin does not come from a pig pancreas and it's not pig insulin, it's human insulin. But it doesn't come from humans. We're not harvesting humans. Not that I know of, not in this country.

• 55:08Speaker 02

  Instead, it comes from a process called fermentation. It comes exactly the same process as we get from a craft brew. So a craft brewery takes in sugar and it takes in yeast and the yeast convert that sugar into alcohol through a series of chemical steps, a series of enzymes that are made. And that comes from the DNA of the yeast cell, the genome of the yeast cell. All the genes in the yeast make enzymes, which are three dimensional molecules, which can make and break other chemical bonds, and out comes alcohol.

• 55:51Speaker 02

  Well, it turns out you can program that DNA now, and that's what Genentech did. And they changed the genes so that instead of making enzymes that made alcohol, they made enzymes that made insulin. So they took the human gene for insulin, put it into the yeast cell, and now they can brew insulin. And so that's at its core what synthetic biology is about. It's about being able to read, write, edit the DNA, find things that you want to make, put them into cells that can make them. And now you have this amazing production platform for making anything you want. And it could be insulin, or it could be a material like a nylon, or it could be a chemical, or it could be a polymer, it could be a food product.

• 56:35Speaker 02

  And this is why we're seeing this boom in synthetic biology over the last 10 years of people now building stuff with biology.

• 56:43David Hoffman?

  So the, a theme I've noticed is that fermentation really seems to be a very key part of this, and that also seems to be where we apply this word programming into. We use this fermentation progress as our programming bed, so that we take this organic process where instead of producing alcohol, we are able to reprogram this, the fermenting process, the microorganisms in this fermenting process to instead produce alcohol, produce something else. And my intuition from what you said is that, okay, we started by changing from alcohol to insulin, but it almost seems like the product of what can be made from this fermentation process could be anything. And that's just because of the adaptability of biology. Is this the right intuition?

• 57:28Speaker 02

  That's right. If you look around us, anything that you see that's naturally produced in nature by biology, theoretically, we can now engineer it and produce it in any way we want.

• 57:38David Hoffman?

  Why, help me understand why fermentation is such a key element here. Can you explain that a little bit?

• 57:44Speaker 02

  Yeah, so fermentation is the process of converting one kind of molecule into another, and it uses, there are different types, but the primary one uses oxygen in the environment. We're aspiring right now. We're breathing in oxygen, and we're using the energy in the oxygen to make and break other chemical bonds inside of us, and we're breathing out carbon dioxide. So that's just a process. And that's the same process that goes on inside a yeast cell, for example, to make alcohol.

• 58:15David Hoffman?

  And so, how have we turned this fermentation process from just like this natural thing that happens, and then we were able to reprogram it to do insulin? How have we turned that into an industry? Like, what are the next steps along this process to really harness this power?

• 58:31Speaker 02

  So we've turned it into an industry because some of these products are quite difficult to produce in nature, or they're very expensive to produce. One of the canonical examples is the autumnic acid, which is this...

• 58:47Speaker 02

  Molecule that is used to make an antimalarial drug. And this is by the work of a guy called Jay Kiesling, a professor at Berkeley. And he started a company called Amorous. And Amorous Biotechnologies made this antimalarial drug. And the way that it's made right now is from this plant called the, a tree called the Chinese wormwood. And you have to extract, you have to grow tons of this tree to extract this tiny amount of the drug. And so what they did instead was to find the pathway that made this molecule, this antimalarial drug.

• 59:28Speaker 02

  And instead they put it into a yeast cell and now they can just brew it in a brewery. Instead of having to grow thousands of trees. So that's kind of the principle of why this thing could be more efficient, better for the environment, lower cost. Is by taking that principle of fermentation and genetic engineering and producing these things via cells. Rather than things that are much more resource intensive out in the land.

• 59:56David Hoffman?

  So the idea here is like using this fermentation process, which we've been able to harness. If we find a compound that's out in nature, we can take that information back. And put it in, and put it in part of this process that makes this scalable, right? And so are we constrained to only be able to produce components that we can find elsewhere in nature? Or can we actually kind of create stuff that's net new without needing to like source the DNA or the solution elsewhere?

• 1:00:24Speaker 02

  We can find things that are new, so there are, it's easier to find things in nature. Because there's such a great diversity out there in nature. I'll give you one other example, which is a company called CheckaSpot. And CheckaSpot has a platform for the production of oil. And oil is being used industrially, bio-based oil. There are only a few production platforms for it. Soybean is one of them, corn is, is one of them, canola is one of them, or rape seed, as it's called in Europe. And CheckaSpot is creating a brand-new platform and they're using algae as this platform.

• 1:01:05Speaker 02

  And the algae are taking in CO2 and they're spitting out this oil. And what this allows CheckaSpot to do is to go out into nature. Now, if we sequence this plant behind me, you would find all sorts of interesting oils in it. But this plant isn't very good at producing lots of the oil. The algae is good at producing lots of the oil. So what do we do? We sequence the genes inside the leaves of this plant. We find out this interesting oil that we want. We transfer it, gene-edit it, or engineer it into the algae. And now you've got as much of it as you want. And so CheckaSpot is making these new performance materials from molecules that are found in nature. And they've made a set of skis, cross-country skis, that have performance properties

• 1:01:50Speaker 02

  that cross-country skiers have been looking for for decades. They can now tune these properties of these materials using things that they find in nature, editing them to make them better, stretchier, stronger, more resilient. So it opens up this whole palette of what's out there in nature. And then you can build on top of that. But right now, there's so much diversity out in nature that people can use. But people are starting to now look beyond nature and see what other kinds of things we can come up with.

• 1:02:20David Hoffman?

  Yeah, I'd like to try and put some, like, fast-forward perhaps a little bit in the trajectory of synthetic biology where right now we're talking about pretty granular specific use cases. But I want to kind of zoom out and see if we can strike the imagination of listeners about how extensive that this could replace previous systems. And so the gist that I've gotten is that we have now this ability to take the best of nature and nature as a problem-solving mechanism can run circles around humans. Now, humans have our certain capacities. We have computers and the internet and things that we can do with that. And that's unique. And combining these things is really the world of synthetic biology.

• 1:03:04David Hoffman?

  But nature really can still run circles around producing cool things that we still have not able to dream of. And so when we extend this out just beyond the granular, how can we explain to listeners how revolutionary this is and how scalable this is and how much it impacts the world around us?

• 1:03:21Speaker 02

  It's a great question and I'm glad you asked it because... The rabbit hole that we're we've gone down is is like one percent. Maybe zero point one percent of what the future holds for biology. The rabbit hole we've gone down is talking about single cells that can produce single molecules or single products.

• 1:03:41David Hoffman?

  Right.

• 1:03:41Speaker 02

  And you are not a single cell.

• 1:03:43David Hoffman?

  Right.

• 1:03:43Speaker 02

  And you are not a single product.

• 1:03:45David Hoffman?

  Yeah.

• 1:03:46Speaker 02

  You are a body that's made of trillions of cells, all connected together, all communicating with each other. From the neurons that are produced in your brain.

• 1:03:56David Hoffman?

  Right.

• 1:03:56Speaker 02

  From the um from the bones that are produced, from the calcium that's produced in your bones.

• 1:04:01David Hoffman?

  Individual organs are symphonies of cells. Yet your body is also a symphony of organs too as well.

• 1:04:08Speaker 02

  You got it.

• 1:04:08David Hoffman?

  Yeah.

• 1:04:09Speaker 02

  And they're all singing and they're all communicating with each other.

• 1:04:11David Hoffman?

  Mm hmm.

• 1:04:11Speaker 02

  So what's amazing, and this blows the minds of computer science people, computer programmers, is that inside each of the each of the trillions of cells that you have in your body is the operating system for that cell. And it's the same operating system running in every single cell in your body. But it's different different subroutines, different programs are being run in the cells in your in your eyes to say, turn into

• 1:04:44David Hoffman?

  Right.

• 1:04:44Speaker 02

  cells that that can sense light.

• 1:04:47David Hoffman?

  Turn photons into neuro firing.

• 1:04:49Speaker 02

  Exactly, to to the to the cells in your in your fingernails, which are saying, grow, grow some calcium. You know, some some uh some some molecule to make my fingernail.

• 1:04:59David Hoffman?

  Right.

• 1:04:59Speaker 02

  It's the same, it's the same genome. So these things that evolve, you know, from from from the moment of conception of of the sperm in an egg, where you get two copies of the genome, half one from your mom, one from your dad, recombine to make the unique molecular. Properties of you, then when they divide and divide and divide, in every single cell is the same copy, but they're turned on and off in different ways. And so now if you imagine, well, what does the future of biology hold? It's not just about picking one gene that's going to make an oil or one gene that's going to make a plastic. It's about how can we actually learn to program multicellular systems?

• 1:05:43Speaker 02

  So that you could imagine, you know, what does, if we wanted to program this iPhone and make it using biology, we could do that. You could, you could, look at all the sophistication that we have in, in, in my body and in my brain. We can absolutely think of a biological iPhone as sophisticated as, as, as the machine that it is. But then the, the amazing thing is that iPhone would be able to produce another iPhone.

• 1:06:07David Hoffman?

  Hmm. I think the, the thing that really struck my imagination when I was listening to the talks the other day is that silicon and computers and metal are, and they're, they're similar in that they have patterns of activity, kind of like a brain. Like, computer is a silicon brain, a brain is an organic computer, these are kind of similar. And then if you look at the underlying structures of like the neural activity of a brain and compare that to the neural activity of a motherboard, like you know which one's which, right? One has like 90 degree angles, one looks like, you, you just know, like the one, a motherboard looks like a motherboard, a brain looks like a brain, it's chaotic, the brain

• 1:06:49David Hoffman?

  and the organic is, the brain's very chaotic and organic and like hard to understand. And then the motherboard is very rigid and like very much made in a factory with like, you know, right, human created angles, like all of this kind of stuff. And like my, the imagination that I was able to like, kind of get when I was listening to these talks is that what's going, what's happening here is that we are, with what synthetic biology is, to me, at least my understanding is of it, is that we can actually program. Nature, the chaotic nature of nature, using our, using our computers, but that we can actually understand and harness the organic and efficient ways of like neural net, the, the neural activity or the way that cells grow.

• 1:07:32David Hoffman?

  And so we can actually, like, nature seems chaotic to us. But to me, synthetic biology is that we can actually start to create that chaos in ways that work for us and that ways that we can understand. Is that, is that a fair, like, summary of this?

• 1:07:46Speaker 02

  Yeah, and I'm glad you brought that up because up until now, your listeners might be thinking, if they know about genetic engineering or bioengineering or metabolic engineering, then they might be thinking, well, what John just described is no different to what we've been doing for the last forty or fifty years, since the discovery of recombinant DNA, the ability to, to, to read, write and edit, edit DNA. And they'd be right. So what is synthetic biology? What's the difference? Well, synthetic biology came about twenty years ago, and it was from a group of engineers coming into biology and saying, biology is not an engineering discipline. Biology is, is, is more a discipline of science, asking questions about, about how things work.

• 1:08:30Speaker 02

  And so they came up with a name called synthetic biology. And I think you're gonna have Drew Endy speak on your podcast later on. And Drew's one of the founders of the field. And he's one of the people who came up with, with calling it synthetic biology. And so I like to say that synthetic biology is a movement to make biology easier to engineer. Drew looked at the process that was going on through genetic engineering and bioengineering. And he said, why does it take millions of dollars to get a product to market? Why does it take seven years on average to get a product to market? Why, when I'm engineering a cell, does it take months to iterate through one single cycle of the design, build and test loop in biology? And this was twenty years ago. Now it takes weeks.

• 1:09:15Speaker 02

  Why is it? And it's because nobody has ever put in the investment to say, how do we make biology easier to engineer? So all the examples that I gave you are wonderful examples of biology, of, of engineering, but they're all really expensive and really slow. And so nobody, Drew said, is, is looking at the system holistically and trying to turn biology into an engineering discipline. When you look at structural engineering, or civil engineering, or environmental engineering, or electroengineering, or software engineering, They've all developed into mature engineering disciplines so that now my eleven year old daughter could write an iPhone app in a few hours. And we want to be in that situation with biology.

• 1:09:59Speaker 02

  And so the field is a movement that has a vision that in the future, we're going to be able to program biology as easily as we can program a computer or a motherboard, as you said. And we're not there. We're maybe one percent into that, into our ability to do it. And what you saw at the meeting this week and at the talks, and whenever you see a synthetic biologist talk about it, there's this burning passion that we know what the future is going to be like, and we want to get there. And so it's this movement of people who are so passionate about how do we engineer biology. And that then enables and opens up a whole range of possibilities for the future of

• 1:10:42Speaker 02

  humanity, for the future of manufacturing, related to climate change, related equity, related to our economy, which broadly speaking, we call the bioeconomy. And that's the big vision for what this, all of this will enable.

• 1:10:55David Hoffman?

  Yeah. John, I think we've tackled the first part of the story, which is like talking about how we can re-engineer fermentation to make specific cells that we want. And then we've also done the other end of the spectrum, which is talking about like the future grand vision of synthetic biology. And I think we skipped the middle ground and I want to try and illuminate some of the not grand vision topics of synthetic biology, but also more complex and single cells. And maybe I can try and start that conversation with like, nature does some things really, really well, that we have found useful for humanity since the dawn of time. Like wood is a very strong structure that we build very big buildings out of, and that is biology.

• 1:11:38David Hoffman?

  It's not synthetic biology, but it's an indication that nature can do some really important things naturally. And think about how many trees there are in the world versus how many things grow steel. Not very many things grow steel. We have factories and there's, you know, a low number of those in comparison to how many trees there are that are growing, growing wood. And so like, maybe we can start to illuminate some of the use cases of when we apply synthetic biology to more complex systems than just cells, and how that can start to change the landscape of the world that we live in. Has any use case come to mind?

• 1:12:12Speaker 02

  So I've got a couple of examples I could show you in terms of cement or in terms of materials. Would that be useful to talk about?

• 1:12:21David Hoffman?

  Sure.

• 1:12:22Speaker 02

  So I brought a couple of props with me. One of the speakers at the event this year, and I'll show it to the camera, was Ginger Kriegdostier. And she's with a company called Biomason. And so we can, maybe you can open that up.

• 1:12:37David Hoffman?

  Sure, yeah, and you can talk about it?

• 1:12:38Speaker 02

  Yeah, so this is, this is a pretty rad example. It's using microbes to fix cement and concrete. So this is a lump of cement that's been, calcium carbonate, that's been fixed using microbes. And so if you know anything about the cement industry, you'll know-

• 1:12:57David Hoffman?

  This looks and feels like normal cement, by the way. I wouldn't be able to tell the difference.

• 1:13:01Speaker 02

  Right. This uses 5% of the amount of CO2 that regular cement uses. Regular cement is one of the most damaging processes in the environment. I think it's responsible for, I think it's 11% of global CO2, something around that.

• 1:13:19David Hoffman?

  I think the figure I heard was four times more than the entire airline industry.

• 1:13:23Speaker 02

  Yeah, which is nuts because it's just giving off, when you cure cement, it's just giving off CO2 all the time. So this is Biomason. They're not using any genetically engineered microbes in this right now, but they have a big program where they're looking at how they can tune the properties of these naturally occurring organisms to make them, to make them better. And there's a video that Ginger showed in her talk yesterday showing how these microbes just kind of wrap themselves in calcium carbonate and use it to crystallize and fix other microbes to make this cement.

• 1:13:54David Hoffman?

  So rather than a chemical process, it is a biological one?

• 1:13:58Speaker 02

  Exactly.

• 1:13:58David Hoffman?

  Right.

• 1:13:59Speaker 02

  Yeah, and all biology is chemistry ultimately. But, but yeah, this is the kind of catalyst to get this going is a biological one instead of a chemical one. Instead of using blast furnaces, instead of using giant kilns, sorry, blast furnaces is steel production. Kilns is for cement production, but incredibly energy intensive.

• 1:14:18David Hoffman?

  Yeah, I think the pattern here is that we are learning through synthetic biology to work- With with nature rather than brute forcing against nature, right?

• 1:14:28Speaker 02

  Exactly.

• 1:14:29David Hoffman?

  In order to make um cement, we need this massively two thousand five hundred degree Fahrenheit, or maybe Celsius, I don't know, really, really hot uh kiln in order to just make cement happen.

• 1:14:41Speaker 02

  Exactly.

• 1:14:42David Hoffman?

  With synthetic biology, it's more of an organic process like of tree of forest growing. It just kind of happens.

• 1:14:49Speaker 02

  Yeah.

• 1:14:49David Hoffman?

  And it happens without much effort and without having to inject energy into it.

• 1:14:54Speaker 02

  Yeah.

• 1:14:54David Hoffman?

  And so it's working in harmony with nature to produce these compounds that we kind of already have. But now we have the same the same ones with uh five percent of the energy it took to get there.

• 1:15:03Speaker 02

  Exactly. And and look around us in nature. Look at my teeth.

• 1:15:06David Hoffman?

  Mm hmm.

• 1:15:07Speaker 02

  Look how hard they are, right? These are gonna last me hopefully, you know, another another sixty years. Um, look at the bones in my body.

• 1:15:14David Hoffman?

  Mm hmm.

• 1:15:15Speaker 02

  Look at uh just being able to regrow things like when when my daughter's tooth came out last week. Well, she's gonna have another one grow. But she's and I told her this is the only

• 1:15:24David Hoffman?

  That's the only one.

• 1:15:25Speaker 02

  You're only gonna get that chance to do it once. Um, so uh but why not? Why can't you reprogram uh uh the cells in your mouth to regrow another tooth? Totally can. Well, why can't you uh reprogram um the the limbs in your body to grow another one? And we heard an amazing talk by Mike Levin about the potential for that as well. So, yeah, there's there's a whole bunch that we're gonna be able to do with these living materials. And if you think, and it sounds like science fiction, but remember the size of a pterodactyl, remember the the size of a T-Rex? I mean, biology can grow big things.

• 1:15:59David Hoffman?

  Right.

• 1:16:00Speaker 02

  Look at a sequoia tree, a giant redwood tree, and then compare it to the structures around us. Well, I mean, we're in a beautiful location. It'd be even cooler if we could have grown this location.

• 1:16:10David Hoffman?

  Right.

• 1:16:10Speaker 02

  And then at the end of its life, you know, have it maintain itself during the life. And then at the end of the life, have it go back into the soil. And and think about that, the the the, again, the climate resiliency that we need. And the, you know, this place is beautiful, but imagine how much concrete went into building this place.

• 1:16:27David Hoffman?

  Right.

• 1:16:28Speaker 02

  So we can build these beautiful, you know, imagine an Ewok village, right? Grown from from biology. Imagine an oak tree or or a giant sequoia where the the seed is programmed to grow into this beautiful sofa that we're sitting on.

• 1:16:41David Hoffman?

  Is that crazy or is that sci fi? Or is that like, do we know the steps of how to do that?

• 1:16:47Speaker 02

  It's crazy. It's sci fi. We don't know the steps how to do it, but Biology is, we are entering the century of biology. And ChatGPT, DALL-E, the iPhone itself, the Apple Watch. These are all pretty sci-fi things if we went back even twenty years ago. And I mean, we were all imagining it. Now it's a reality. All of the biologists know what's capable. We don't know how to do it right now. There are still, we still don't know what like sixty percent of the genes in a, in a single E. coli cell do. And there's still a ton of communication that goes on between cells that we don't understand and can't measure. But we're getting there.

• 1:17:32Speaker 02

  And particularly with AI, the problem has been that we can't do these loops of design, build, test, quick enough to gather enough data. Many people think we're still at the punch card phase of biology where we're putting, in the sixties, they were using cardboard punch cards to program computers. We're about there with biology right now. But in the twenty years that I've been in the field, we've seen these giant leaps and bounds in our ability to engineer biology. And now also you're seeing a ton of tech money come in. There was like eighteen billion dollars invested in the synthetic biology industry in the, in the, in twenty twenty one. About ten billion dollars in twenty twenty two. And, and I write a weekly newsletter, we put out an annual investment report. So I, I know the numbers and I see the trends.

• 1:18:17Speaker 02

  And we're entering the century of biology and our ability to, to do this is just speeding up nowhere.

• 1:18:23David Hoffman?

  Yeah, you, you said, you talked about how we could grow this building or we can grow this couch. And that probably threw at least a handful of listeners through a little bit of a tizzy because that's a crazy concept. But I want to remind listeners that like the DNA that they have grew them. And I think that's really just the idea of synthetic biology is we can reprogram DNA to grow things. And because we have this computing platform that's open to us, which is now biology. We can create DNA that grows into a couch or grows into a building. Or, I mean, maybe it's kind of hard to imagine, but that is the vision here is that we, we have this very tight packet of data.

• 1:19:04David Hoffman?

  That when you let it grow like a tree, it grows into the shape that you want it to become. Is that, that's the idea, right?

• 1:19:10Speaker 02

  Yeah, and it's, and it's called programmed pattern formation. And it's an area of research. And again, we're not, we're not there yet. It is science fiction. But I believe that we're gonna get there.

• 1:19:20David Hoffman?

  You've got another example over there, a jacket that came from, I don't know what it came from. Maybe you can show it, tell us the story of how this jacket came to be. We did not, this jacket was not grown, but parts of it were, I think, right?

• 1:19:33Speaker 02

  Absolutely. So this is a beautiful Adidas jacket. We'll do some product placement here, free product placement for Adidas. But even more importantly, it's made by a polymer that's made by a company called Lonzatech. And Jennifer Holmgren was the speaker, and I think she's gonna be on the podcast.

• 1:19:50David Hoffman?

  Yeah, we've had her, she's got an episode as well, so you'll hear from her soon.

• 1:19:53Speaker 02

  Okay, so she gave one of these to Vitalik Beiderin during the conference yesterday. And so this is one of the products that I love and one of the stories that I love. Because this is made from polyethylene. And polyethylene is made by Lonzatech. And Lonzatech, it's a reversible jacket, so it's kind of got a funky futuristic.

• 1:20:19David Hoffman?

  I think we know which side Vitalik was wearing.

• 1:20:20Speaker 02

  Exactly, exactly. So Lonzatech is doing what we were talking about earlier. They're doing fermentation, and they're growing things inside of steel mills. So steel, again, through blast furnaces, is just producing a ton of CO2, waste CO2. And they're taking the off gas of this CO2 coming from steel mills, and they're putting it into their fermenter. And they're bubbling this CO2 through the fermenter. And inside the fermenter, they're growing these specialized organisms. And these specialized organisms are feeding off of that CO2. And they are producing a whole number of different molecules.

• 1:21:05Speaker 02

  They can produce polyethylene like this, they can produce ethanol, which can be used as fuel. They have a partnership with Virgin Atlantic. They have another partnership with Alaska Airlines. They have another partnership with Lululemon, another partnership with Zara, the clothing brand. So they can have this versatile platform that takes waste gas of CO2 coming out of the power plant, bubbles it through these microbes, and the microbes now are... Producing the enzymes from the DNA that's in their genome and turning that CO2 into into this product that we can see here. So it's a wonderful story of showing how we can create these circular ecosystems. And Jennifer made a good point in her talk yesterday. She said, we have enough carbon in the atmosphere.

• 1:21:48Speaker 02

  We do not need to be sucking this up and burning it. We do not need coal. We do not need oil. We can be producing things from the CO2 in the atmosphere. And this is a great example of it.

• 1:21:59David Hoffman?

  Yeah, I think really the message that I got out of that is with synthetic biology and this new like computing manufacturing platform, which is the cell, which is biology, not only can we customize the outputs, but we can also customize the inputs too.

• 1:22:14Speaker 02

  Right.

• 1:22:15David Hoffman?

  And so it doesn't, that's the full, the full cycle, right? That's how we have a cyclical economy, a cyclical ecosystem.

• 1:22:22Speaker 02

  Exactly.

• 1:22:23David Hoffman?

  Because you can compute on both sides.

• 1:22:24Speaker 02

  Yeah.

• 1:22:25David Hoffman?

  And so it's, it's the full suite of possible applications, both on the inputs and on the outputs to create the products that we want.

• 1:22:32Speaker 02

  Exactly. And let me give you, you talked about compute and, and a lot of computational people, a lot of computer scientists, they've heard that biology is programmable. I want to give some examples of how biology is programmable and the kinds of things that we might be able to do. One is the circadian rhythm in your, in your body. We're probably both a little bit jet lagged, having just flown in. And you know, it's like, why am I waking up at 2:00 AM wide awake? Well, it's because your body has an oscillator in it, a, a cycle that goes up and down, up and down, telling you when to be awake and when to be asleep. And it's all going on because of the way that the molecules bind to the receptors in your brain to tell it, now's time for bed.

• 1:23:15Speaker 02

  And then they release over time and it says, now's time to wake up. The same thing happens with. Uh, dopamine and with serotonin, the drugs that make you feel happy. If you've ever kind of gone through real kind of, you know, we, we've been very stimulated the last two days. It's just been, you know, kind of a little bit like, okay, now I want to chill out because when you go to a conference and there's just so much stimulation, so much coffee or good food or great conversations, um, or alcohol or what have you. Well, your body's being kind of blasted with all these, all these stimuli and you don't wanna, you don't wanna overdo it. You, you, so there's systems, particularly for dopamine, for the reward system, where you have a natural cycle.

• 1:23:59Speaker 02

  And this is, you know, this is why some people get depressed and some people get in these episodes of, of mania, is all to do with the binding of dopamine to the dopamine receptor. So you have these oscillators where they bind and then they release slowly and then they bind again. And so this is why setting goals in your life is, is really important. And, uh, you know, I want to do that. A, a simple example is I'm hungry, I can smell some food. Okay. My brain is like, go towards the food and it puts the dopamine trail out there. Now, as soon as I've eaten, gone. Right. I'm not, the dopamine is gone. I'm not interested in, in eating anymore. It's an oscillator. It's, it's the, the binding of the dopamine to the receptor and then the slow release of it.

• 1:24:40Speaker 02

  And just to kind of close the loop fully, this is why, uh, things can be so addictive. Drugs, um, um, gambling, sex, people can get addicted to these things because they just want more and more and more. And, and it kind of breaks the natural cycle of the oscillation. So it's a simple example of, of how oscillation works in terms of, uh, setting up a computational system inside of a cell. What's really interesting that in the year 2000, there was a, an important paper published by, by Micah Elowitz at Caltech, which showed creation of a synthetic oscillator inside a E. coli cell. And he produced glowing bacteria, fluorescent bacteria that, that, that on this beautiful

• 1:25:23Speaker 02

  20 minute time lapse, you can see videos of it online, uh, made these fluorescent bacteria glow and, and shrink and glow, glow and, and go down. Dark and glow and go dark. It was just a beautiful example of a very simple pattern that we knew existed, written into a gene circuit that didn't exist in the bacteria and program it to do something very simple in an engineered way. And that was one of the first examples of synthetic biology. It was 20 years ago. And on the front page of, I think, Nature or Science, it said, you know, the, the, the, welcome to the era of synthetic biology.

• 1:25:52David Hoffman?

  Beautiful, beautiful. Okay, so here we are in 2023.

• 1:25:57David Hoffman?

  Place us into the arc of history of, of synthetic biology. Like where, where, what is this moment that we are currently living in? And how can, how can listeners expect synthetic biology to find their way into their lives in perhaps the next few years?

• 1:26:10Speaker 02

  Yeah, you know what? I think the term will disappear in, in, in 10 or 20 years. Just like the term, you know, look at the terms like, like, uh, high tech.

• 1:26:21David Hoffman?

  Right.

• 1:26:21Speaker 02

  Look at the terms of web 2.0.

• 1:26:23David Hoffman?

  Right.

• 1:26:23Speaker 02

  These things come and go, and soon it's just going to be biology. It's like, well, of course this is made with biology. Why on earth would you want to make it with a petrochemical?

• 1:26:31David Hoffman?

  Right.

• 1:26:32Speaker 02

  Um, well, of course.

• 1:26:33David Hoffman?

  So antiquated, so inefficient.

• 1:26:34Speaker 02

  Exactly. It's like, it's like, really? You made this beautiful wooden, wooden sofa by cutting up a tree?

• 1:26:40David Hoffman?

  You killed a tree?

• 1:26:41Speaker 02

  Exactly, yeah. There was a paper, a big announcement last week about, uh, plants hearing, being able to hear plants scream when you, when you hurt them. I don't know if you heard that.

• 1:26:52David Hoffman?

  No, no, I did not, no.

• 1:26:53Speaker 02

  That was pretty rad. So, uh, so, yeah, I think we're going to look at things and, and, and the bioeconomy and biotechnology are just going to be integrated into, into our everyday lives. So I, I think that's a really important thing. I think the other thing that's important to recognize, the reason that we're here, the reason why we ran this workshop this weekend, and, and the workshop, to be clear, was on the bio network state. How can we create future network states that are built with biology? Because many of us in the synthetic biology industry see the potential of biology and, and we see these incumbent industries like the oil and gas industries, and we see a much brighter future. And so. A future that's literally built with biology,

• 1:27:38Speaker 02

  where we can create economies that link their funding to scientific advances, and particularly the scientific advances of biotechnology, and then can use those technologies to create sustainable economies. So for us, it's all about sustainability. It's all about equity. It's all about the means of production and reducing the impact of climate change. And so what we did this last couple of days was bring together the DSCI community, the decentralized science community, which is all looking at funding of science, publication of science, commercialization of science, and how that can be done in an equitable way. Because all of these systems are broken. The economy is broken. Democracy is broken. Science funding is broken.

• 1:28:23Speaker 02

  Publication system is broken. Peer review is broken. All these things are broken. And I look at the decentralized science world and believe that that is a technology. Blockchain is a technology that can fix it. And it can spread out the benefits of these, of what we're doing to the people who are participating in the network. So that's why I'm big on decentralized science. The network state, I'm big on because I think that solves a lot of the core tools around our democracy that are broken. And then the tools of synthetic biology and the community of synthetic biology, I think, has the ability to fix it. So that's what I think is so exciting about the next decade, is the combination of all these things coming together

• 1:29:05Speaker 02

  to create a better future and one that's built with biology.

• 1:29:09David Hoffman?

  Well, John, we started at the top of the synthetic biology rabbit hole, and we are ending, and you are dropping us off at the network state and DSCI rabbit hole. So thank you for ending us and putting us there because I think that is going to be exactly where our listeners are going to hopefully venture off into these new information frontiers. So thank you for guiding us on the synthetic biology rabbit hole. I really appreciate it.

• 1:29:29Speaker 02

  Absolutely. I'd like to welcome all of your listeners to the conference that we do. It's coming up May 23rd to the 25th, 2023 at the Oakland Marriott. And we have a whole section on decentralized science. And we have a whole section on all of the other areas of synthetic biology. There's about 2,000 people that come together at the conference each year. And there's also a weekly newsletter. So if they want to geek out. And we also have actually two, two courses on the first day of the conference. One is an introduction to DSI, decentralized science. And the other one is an introduction to synthetic biology. So we're completely welcome to new people coming into our field and, and getting excited about what the potential is.

• 1:30:06David Hoffman?

  One more time on the dates and the location.

• 1:30:08Speaker 02

  It's, uh, it's, uh, May 23rd to the 25th, uh, in the Bay Area, the Oakland Marriott.

• 1:30:14David Hoffman?

  Awesome. John, thank you so much.

• 1:30:15Speaker 02

  Absolutely. Thanks for having me.

• 1:30:16David Hoffman?

  Cheers. Appreciate it. You know Uniswap, it's the world's largest decentralized exchange with over 1.4 trillion dollars in trading volume. You know this because we talk about it endlessly on Bankless. It's Uniswap, but Uniswap is becoming so much more. Uniswap Labs just released the Uniswap Mobile Wallet for iOS. The newest, easiest way to trade tokens on the go. With Uniswap Wallet, you can easily create or import a new wallet. Buy crypto on any available exchange with your debit card with extremely low fiat on-ramp fees. And you can seamlessly swap on mainnet, Polygon, Arbitrum and Optimism. On the Uniswap Mobile Wallet, you can store and display your beautiful NFTs. And you can also explore Web3 with the in-app search features, market leaderboards and price charts. Or use Wallet Connect to connect to any Web3 application.

• 1:30:59David Hoffman?

  So you can now go directly to DeFi with Uniswap Mobile Wallet. Safe, simple custody from the most trusted team in DeFi. Download the Uniswap Wallet today on iOS. There is a link in the show notes. Are you planning to launch a token? Is your token already live? And are you granting your employees and contractors vesting token awards? And are you trying to figure out how to take care of taxable events for your team? Toku makes implementing a global token incentive award simple. With Toku, you will get unmatched legal and tax support to grant and administer your global team's tokens. Toku will help you navigate across the lifecycle of your token. From easy to use pre-launch token grant award templates to managing post-cliff taxable events with payroll. For legal, finance and HR teams, it's a huge, complex task. To have to comply with labor laws, payroll and tax obligations, tax reporting and crypto

• 1:31:43David Hoffman?

  regulations in every country that you employ someone, it's difficult, time-consuming, manual and costly, and it's drawing more attention from global regulators and governments. Toku makes it simple for leading companies in the space, Protocol Labs, Hedera, Gitcoin, and many more, to manage their token complexities. So, if you are interested in signing up with Toku, check out toku.com/bankless, or click the link in the description below. We are at Zuzalu, and I am talking to Jennifer Holmgren of Lonza Tech. Jennifer, thank you for joining me.

• 1:32:11Speaker 03

  It's such a pleasure. Thank you for having me.

• 1:32:13David Hoffman?

  Jennifer, I watched your talk this morning, and it was extremely inspiring. And a lot of the content and conversations that's been going on here at Zuzalu is really a systems-level thinking. And I'm hoping we can start with the problem. And the interpretation of the problem that I got from watching your talk was that the way that we have our materials, our goods, our manufacturing, and our energy.

• 1:32:37Speaker 03

  Yeah.

• 1:32:38David Hoffman?

  The basic pattern is that we pull carbon out of the ground to make our widgets, to power our planes.

• 1:32:44Speaker 03

  Yeah.

• 1:32:44David Hoffman?

  And then we consume them. And when we need more, we pull more out of the ground.

• 1:32:49Speaker 03

  Right.

• 1:32:50David Hoffman?

  And so, to summarize the problem, perhaps, it's a one-way flow of carbon from the ground into the air.

• 1:32:55Speaker 03

  Yep.

• 1:32:56David Hoffman?

  And so, can you just elaborate on this problem, and what it means for this world? And we'll eventually get into what we need to do about it.

• 1:33:03Speaker 03

  Absolutely. So, the first part of the story, of course, is that we need a more circular economy, right? That we need to be able to not do exactly what you said. Take something out of the ground, make it into something, waste some of it along the way, and then dump it into the air, or into our oceans, right? Because some of the solids end up floating in our oceans. It is a systems problem, because it's impacting our entire ecosystem and all of the things that are interrelated. I think that the most important thing that we can start to do is to say we're going to reuse everything we do. We're going to be more like nature. Nature is circular, right? Even a tree will drop a bud, and the bud will become the next tree, right? Nothing is wasted. We waste a lot of things. So, our

• 1:33:48Speaker 03

  view is that we have enough waste carbon above ground. That we should just keep reusing that rather than taking more carbon out of the ground. And this circular economy approach, this new carbon economy, if you will, will be less wasteful and will stop dumping carbon into our atmosphere, helping us with the climate crisis.

• 1:34:07David Hoffman?

  I think one of the the big problems about that problem is the universality of the way that we do this in that all goods, be it plastics or materials or clothes, like pick your industry, it's the same problem, which means it goes to such like a root level to the problem is so deep.

• 1:34:27Speaker 03

  Yeah.

• 1:34:28David Hoffman?

  Which means the solution also has to be similarly as deep. This the solution needs to be equal or below the problem.

• 1:34:33Speaker 03

  Yeah.

• 1:34:34David Hoffman?

  And so can you talk about this like just design space for making sure we go all the way down to the bottom?

• 1:34:38Speaker 03

  Well, first of all, I don't think most people know what you started with, right? That all of this pollution, all of these things that we have actually come from fossil carbon. Most people don't know that that's where the tennis shoes come from, right? And so I think the first thing we need to do to have a system solution is to really say, look, people need to understand where everything comes from. Everybody knows power, fuels come from fossils, but what about things? And and then we just need to be conscious of that. But I think then the next layer is, okay, if we're gonna make all these things and we can't make them from fresh fossil carbon, what am I gonna make them from?

• 1:35:19Speaker 03

  And and that's where I think new technologies that can use waste carbon, things that you would call pollution, like we use industrial waste, we use solids like trash, that's where it all comes in, right, is is that. But if you're gonna use waste, you have to use distributed systems, right? There's not enough waste to aggregate in a massive refinery location. If you're gonna use waste, you need to be very selective because you don't want to put too much steel in the ground in these distributed systems, that's too expensive. And that's where biology. Has a fundamental advantage. Biology is selective. Biology can handle inhomogeneity like in waste.

• 1:36:03Speaker 03

  And therefore biology is ideally suited for a new carbon economy. Where we use pollution already above ground to make everything.

• 1:36:12David Hoffman?

  Right, so going back to that original one-way flow of carbon. What you're saying is it's biology that takes is the missing piece of the path that goes from a one-way flow to a circular flow. Can you just elaborate on that?

• 1:36:24Speaker 03

  Well, I think I don't think biology is the only thing that can do this, but I think biology can have a big role to play. And you know biology is very selective. Okay, when you use biology, you make one product and you make exactly the product you want. And so what that means is that you can go from a waste resource and make only one product, which helps you with economics. If you're making a variety of products, it gets very expensive to then continue to process and continue to process. So biology is important. And I think the second and perhaps even most important part of why biology will help us here is biology handles chaos really well.

• 1:37:06Speaker 03

  It's like you're driving down the street and there's this car here and this car here and you know this guy's gonna cut you off and you can maneuver around it. And you know, waste is chaotic. And so the ability to interpolate, the ability to think across things as they change, like a waste feedstock will change, is gonna enable is gonna be enabled by biology. Processing those inhomogeneous feedstocks, biology will help.

• 1:37:36David Hoffman?

  Yeah, so just to really say that in different words, to make sure I understand, it's like you said, waste is not homogeneous. It's different. Like what you throw in the trash yesterday is gonna be different from what you throw in the trash tomorrow. And that is true on a global perspective.

• 1:37:51Speaker 03

  Absolutely.

• 1:37:52David Hoffman?

  And so the solution of making sure that we actually recapture our own goods needs to be able to account for that chaos. And you're saying that biology is good at accounting for that chaos.

• 1:38:03Speaker 03

  Exactly, exactly. Organisms, living organisms, adjust and so they can handle chaos.

• 1:38:09David Hoffman?

  Okay, so let's go into some specifics because we're talking about like very large. We're zoomed out and I want to zoom in a little bit. Lonzatech and this actual biological solution. What is it?

• 1:38:21Speaker 03

  Yeah, okay, that's a great question. So we ferment gases, okay? So you're used to making beer out of sugar, right? With yeast. We make beer out of carbon dioxide, you know, waste gases and bacteria. And we've developed a very efficient way of doing that. And so literally we have gas into our bioreactor. Our bacteria eats it and basically produces ethanol. Quite efficient.

• 1:38:50David Hoffman?

  Ethanol.

• 1:38:51Speaker 03

  Ethanol, yes. And we've made that from ferroalloy gases. There are waste gases in ferroalloy mills, waste gases in steel mill. These are gases that would normally go up into our atmosphere as particulate emissions and CO2. We're preventing that from happening.

• 1:39:07David Hoffman?

  So the first application of your company Lonzatech is in like mills, like large scale factories?

• 1:39:13Speaker 03

  Yeah, so we're going first for the industrial gases and the reason for that is you can just take an industrial gas and put it in a bioreactor. If we wanted to use household waste or trash, we have to turn it into a gas and that costs more money. And so, you know, when you're doing a new technology, you need to get down the cost curve and you do it in the cheapest way possible.

• 1:39:36David Hoffman?

  So you've gone out to these large scale factories that are producing the gas because that's your input. They're making, their output is your input.

• 1:39:43Speaker 03

  Exactly. And we put our plant right there.

• 1:39:45David Hoffman?

  Right.

• 1:39:45Speaker 03

  So we don't want to move these gases. They're already waste, right? And we don't want to clean them up and move them around. So we just put our technology right there.

• 1:39:54David Hoffman?

  Right, so it's like a little like plugin or an add-on to a different, somebody else's factory and that is your input. Do you work, are you just, do you buy their gas or how does that work?

• 1:40:07Speaker 03

  Yeah, so, so you know, if you use something like carbon monoxide, it has residual energy and so you pay for the gas at its energy value.

• 1:40:19David Hoffman?

  Right.

• 1:40:20Speaker 03

  And...

• 1:40:22Speaker 03

  Typically, we pay for the gas, we pay for the land, we pay for the utilities, you know, power, etc., and away we go. But in many cases, we license our technology. So we put our factory up to your factory, but you build it, you own it, you make the product, you use it. So we use different approaches, but typically, most of our partners today have licensed the technology, so it's actually their plant. We're plugging in a plant that becomes their plant into their plant, into their system.

• 1:40:52David Hoffman?

  So you capture their exhaust.

• 1:40:54Speaker 03

  Yep.

• 1:40:54David Hoffman?

  And then it goes into a fermentation system.

• 1:40:57Speaker 03

  Yeah.

• 1:40:58David Hoffman?

  To produce ethanol.

• 1:40:59Speaker 03

  Yeah.

• 1:40:59David Hoffman?

  And this is, this is the beautiful thing about us thinking in a systems-level solution, is that the fermentation is the biology part, right?

• 1:41:06Speaker 03

  Yep.

• 1:41:07David Hoffman?

  And so, uh, this, this works for all, all of these generic gases that are coming out of power plants, and then out your system and your technology outputs ethanol.

• 1:41:17Speaker 03

  Yes. And then, yeah, and then we take the ethanol and using known technologies with known partners, we take that ethanol and make things like the jacket you saw today. We make polyester like for Zara dresses, detergents for Unilever. So basically, what we're doing is, we're taking that ethanol and not using it just to blend with gasoline, um, because hopefully there won't be that many gasoline cars in the future. But also, it becomes a raw material, right? The ethanol is an intermediate to make sustainable aviation fuel, to make materials, to make things we need.

• 1:41:53David Hoffman?

  Yeah, so is it fair to call like ethanol just a very basic building block that is in so much of our world?

• 1:41:59Speaker 03

  It's actually ethylene. So ethylene is the very basic building block. It's the largest-used chemical today, and it's the raw material for almost everything we use, from foam to polyester to plastic. And so what we're doing is displacing that by using a recycled carbon ethanol. That ethanol is converted to ethylene quite easily, actually, and then the ethylene is used for everything.

• 1:42:25David Hoffman?

  Yeah, and it really becomes obvious how deep we are in this stack where we have carbon output from exhaust from a plant going into a carbon, another carbon output.

• 1:42:35Speaker 03

  Yeah.

• 1:42:35David Hoffman?

  That's not a gas anymore, but is now an actual solid.

• 1:42:39Speaker 03

  Exactly.

• 1:42:39David Hoffman?

  And that it becomes, and there's, what I'm learning about is that this ethylene is the building block because it's, I'm assuming, also very deep in like the carbon stack, as in it's a part of so much because it's such a useful compound.

• 1:42:54Speaker 03

  Absolutely, absolutely. It's one of the key raw materials for all of the things we use and so we're just finding a different way to make it. From waste carbon to a key raw material that is used to make everything we need.

• 1:43:09David Hoffman?

  Yeah, viewers or listeners of this podcast are at a slight disadvantage because when I was watching your talk this morning, you were able to put up a slide that had all of these use cases.

• 1:43:16Speaker 03

  Yeah.

• 1:43:17David Hoffman?

  And it was, you also brought this Adidas jacket that was made from this process that we're talking about. And then there was perfumes, there was jet fuel. And I think maybe even just like listing these use cases is also kind of missing the point because the idea is that it's generalizable for everything, right? It is the world around us.

• 1:43:38Speaker 03

  Absolutely. I think that's a great way to think about it. And, you know, you have to get past the yuck factor. This was gonna be something disgusting that was going into our atmosphere and instead it's this beautiful Zara dress, right? And you get past that and then you realize, well, why aren't we just using all of the carbon that's already above ground and recycling it? And I think that that's really the message. And the system is that we've knocked our planet a little bit out of whack because we have this linear economy and Mother Nature is not linear at all. So we just need to be more circular and be more like nature and not waste anything. And we'll get ourselves back in equilibrium.

• 1:44:19David Hoffman?

  And so the, I'm assuming just because it made raw business sense, you start by plugging in your technology and your factories into other people's factories to capture that because that's just easy. But the next step is to capture other materials, I'm assuming. Can you take us down that path?

• 1:44:36Speaker 03

  Sure, so we can look at things like taking trash from a municipal solid waste site and converting that, and we've done that. We've done single apparel, so like shoes. We've converted shoes back to material that could be turned into shoes again. And we've got a relationship with Bridgestone, trying to go from tires back to tires. Because tires, there's a lot of wasted tires out there. You see a lot of trash that has tires. So those are the types of use cases with solids. We also are doing a use case in India on agriculture waste. You know, they normally burn the fields in India, creating a lot of pollution.

• 1:45:18Speaker 03

  And here, instead of burning the field, we're gonna take that product, you know, that waste agri residue, put it in a gas fire, convert it to a gas, and then convert it to ethanol.

• 1:45:30David Hoffman?

  Very cool, very cool, yeah. And so how does this scale out to the world? And so maybe we can talk about the economics of this solution and just the overall plan of taking this from just a few factories to all the factories and to everything else. Carry us forward for the next like 10 years or so.

• 1:45:47Speaker 03

  Well, it's a little bit like solar right and cellular phones, right? You start with some very expensive units. These units are on the order from 50 to 150 million dollars each. So it's very capital intensive. But the more you build, the cheaper they get because you learn how to make them cheaper. So we've done a tremendous amount of work in reducing the amount of metal we use when we build these plants and making the process more efficient, right? We're just at the beginning, nobody had ever done gas fermentation. So we're just at the beginning of the learning curve. And so I kind of think of it as you go from one to two to three, and then eventually you get to 25 or 30. And then they really just start going exponentially everywhere because you've reduced the cost and you made it efficient

• 1:46:33Speaker 03

  and you made it easy for people to use, right? The first time you build something like this, a bit clunky. So you also improve that and make it easier for a lot of people to run it.

• 1:46:45David Hoffman?

  Are there any specific big obstacles in the way? Like, what are the big, uh, why aren't we there yet, for example? Or is it just a matter of time?

• 1:46:53Speaker 03

  I think it's just a matter of time. Um, I don't think there are any major hurdles.

• 1:46:57David Hoffman?

  There's no, like, regulation? There's no, like, resistance from nation-state stuff? There's no incumbents?

• 1:47:02Speaker 03

  Well, there's always incumbents, right? That don't want you to do this. And everybody wants to compare your approach to the incumbents. And this isn't gonna scale the way an oil refinery will scale because waste is distributed. And so you always get a lot of negativity around whether distributed systems can work. But you go through that with everything we've been talking about here. Do distributed systems work? Quite frankly, when you see success of farm-to-table and all of these other things, those are all just distributed systems. We're all just learning to create shorter supply chains, right? Rather than these massive centralized structures.

• 1:47:38David Hoffman?

  Certainly, yeah. And, uh, I think one of the cool things that I saw from your slides was the idea that this technology, I mean, it's just technology, right? It can be in Asia, it can be in Africa, it can be in America, it can be South America. And that's really where we go and, and, because we have to fight this front. Wherever we pull out carbon, instead, there needs to be this technology.

• 1:47:58Speaker 03

  Yep.

• 1:47:59David Hoffman?

  Um, and I'm wondering if we can just, like, end this, end this interview at the very beginning, which is going back and talking about cells and the fermentation. It's so crazy that that's such a small part of this conversation. Of just like, oh, we just ferment, we just ferment it.

• 1:48:13Speaker 03

  Yeah.

• 1:48:13David Hoffman?

  How, it's crazy that that, it's that simple. Can you talk about, just like, let's go back to the biology? Because I'm, uh, my, the listeners of this podcast will understand I'm a big plant guy. I've got a lot of plants in my apartment.

• 1:48:23Speaker 03

  Okay.

• 1:48:23David Hoffman?

  Yeah. And so, like, the fact that this is a biological process, I think, is just extremely compelling. Uh, how, why, why did it take us until, like, twenty? Well, I'm sure you've been working on this for quite a long time. But why haven't we discovered this science sooner? And is it really that magical?

• 1:48:39Speaker 03

  That's a good question. So I'm gonna say, you know, there's a lot of things we have to do to make it work, right? So we had to really optimize the bacteria. It actually normally makes acetate, not ethanol. We had to optimize it to make a product we wanted to sell. We had to develop a bioreactor. So, you know, sugar's soluble in water, right? You, you know, so yeast can grab it and eat it and make ethanol. These gases are not soluble in water. So one of the tricks of the trade is actually the bioreactor, the engineering work that goes around to house that bacteria and make it happy and make it grow. And then the third thing is how do you wrap a whole process around it to make it cheap?

• 1:49:22Speaker 03

  You know, you're not going to pump this bacteria full of vitamins because if you do, it's going to be too expensive. And the process will be too expensive. We recycle the water, we do all these things. It took us seventeen years to get to where we are. So it's a lot of work and it's something, by the way, that everybody said couldn't be done. Everybody said, people knew about gas fermentation. You can't scale gas fermentation. Well, we did. And...

• 1:49:47David Hoffman?

  With some time, yeah.

• 1:49:48Speaker 03

  Exactly. We kept working at it and we had a lot of very smart people, both in the biology side, the engineering side, and we got it to work.

• 1:49:57David Hoffman?

  Jennifer, maybe we can just put on our sci-fi storyteller hat here. And what does the world look like in twenty years when this technology and industry just becomes the status quo? Tell us about this potential utopia that awaits us.

• 1:50:11Speaker 03

  Well, I think it's utopia in that we need to get to gigatons of, you know, we need to prevent gigatons of carbon from getting in our atmosphere. And I think the only way we're going to do that is if we make a conscious choice, that whether with our technology or other technology, our technology is not going to save the world. We need a collection of technologies. And we imagine technologies where everything is recycled. We imagine that you're not going to throw your shoe away. You're going to send it back to the store and it's going to be turned into another shoe. And different business models, different ways of thinking about how we use things, how we dispose of them.

• 1:50:53Speaker 03

  That's my utopia, is there's no such thing as waste. We like to say, "Welcome to the post-pollution future."

• 1:51:01David Hoffman?

  Beautiful. Jennifer, thank you so much for guiding us there. I appreciate you coming on and giving us your time.

• 1:51:05Speaker 03

  It was a true pleasure. Thanks for asking me.

• 1:51:07David Hoffman?

  Cheers.