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!
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 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
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 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 
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 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 

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 SYNBIO for short.

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 3 of the biggest leaders in the synthetic biology world, including Drew Endy, the father of modern synthetic biology.

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 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.

It's just a matter of how do we get the biological components to actually ingest the new DNA that we write like 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 frontier of technological production that we've never had before.

So, Bank of this Nation, take a moment to look around you.

Do you see all the material goods that you have?

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.

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 the 3 leaders that you're going to hear from the synthetic biology world, starting with Drew Endy, the father of modern synthetic biology, followed by John Cumbers, founder and CEO of SynBioBeta, and finished up by Jennifer Holmgren, the CEO of Lanzatech.

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.

Then we'll get to hear from John Cumbers, 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 Lanzatech, which is perhaps the largest in production efforts of synthetic biology.

Lanzatech is a company that depends on an additional facility to a carbon emission source like a steel mill or a landfill.

And Lanzatec captures the emitted carbon and using fermentation, that pollution is converted by bacteria into very simple composable chemical Legos that can be produced into almost anything.

During Jennifer's presentation at Zoozaloo, she pulled out 3 Adidas jackets that were made in partnership with Adidas that had all been manufactured using emitted carbon, 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, 3 of them.

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 purpley rainbowy pink color and like I Was watching Vitalik do this and I realized that he didn't know that it was reversible because knowing Vitalik He would have 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 and it was a very very classic Vitalik moment.

Anyways Small small little snapshot of life at Zusalu 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.

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Bankless Nation, we are here at Zuzalu and I'm talking to Drew Endy, who I have been told is the father of modern synthetic biology.

Ah, when something gets going, there's many parents.

know, and some of the things that are happening with stem cells, by the way, you can have interesting parentage these days.

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?

And go back in time, and let's use the Greek version, synthesis with a U.

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.

So, a lot of times when people encounter biotechnology, it's very much, as an emerging technology, a doorstep of last resort.

You have a horrible disease, you can't cure it by going to the hardware store and buying nuts and bolts.

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 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 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, something's changed, but you don't know what it is.

So it sounds like, to regurgitate some of this back at you, I'm getting ideas of building blocks.

And it sounds like we're going very, very deep in the biological stack to be able to 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 We 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.

Yeah, it's a fair way of representing it, but I want to give everybody a sense of where the frontier is.

So we're doing that work, we're about 20 years into it, it's not a done deal.

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 done.

So for example, biology is a general-purpose technology.

Anywhere you are, you could look at what biology is doing.

It's like, well, could I partner with biology to do more of that or something different?

It's a self-assembling solar panel that recycles itself.

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.

The fundamental unit of life is the cell.

There's no cell on earth that is operationally understood completely.

So the best understood cells have about 20 to 30% 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 going to be Edisonian.

It's going to be tinker and test, tinker and test, which is why you see this investment in foundries and bio works that allow for high throughput tinker and test.

As a long ago structural engineer, I prefer design build work to design build test, design build test.

Like if I'm going to build a bridge, I'll design it, I'll build it, the bridge is gonna work unless I'm incompetent.

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 at the root level.

And so that's where my academic day job with a lab is 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 1, 000 days, like it's a this decade sort of thing, then we begin to see an even more interesting domain of biotech.

I think where these worlds, where these 2 worlds collide, biology and computers, And I think our listener base is pretty intimately aware with how computers work Where they where they collide and what you're saying is that cells are decently like computers Except we are missing like 30% of the motherboard We don't know 30% of the components that make these things work and that is the obstacle that the world of synthetic biology is currently facing.

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

I prefer the metaphor of a cell as a cell.

Metaphors are wonderful and they're dangerous.

So, something to think about is, 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.

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.

You know, like there's hardware, there's software, there's wetware.

But we should talk about it more specifically.

So for example, let's say I took a bacterium that's microscopic, 1 millionth of a meter long, a micron, and I'm just gonna have a magic wand.

I'm gonna make it 100 million times bigger.

I'm not adding more atoms, I'm just like magically making everything bigger.

Let's say I've got a protein, a green fluorescent protein that makes a green light.

That protein is the size of a basketball.

And then the ribosome, which is a collection of molecules that makes proteins, is 2 meters tall.

And then the genome, the DNA, it's going back and forth in this building

It's really thin thread, and so it's cross-sectional areas, like 4 square meters, right?

And then there's many other molecules in this building, all about basketball size, and they fill 30% of the space of the building.

So it's 30%, we call that volume fraction.

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.

It's instantaneous velocity is faster, probably.

It's like, all right, So what that means is the molecular-molecular collision time is a nanosecond.

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

minutes, it can make a physical copy of itself.

I know it's a lot to think about and I like making it macroscopic.

By the way, I would love for somebody to-

I fall into the rabbit hole of metaphor all the time.

But we just got to get to wetware on our own terms.

So that's what I really want to just get for that.

And I think the motivation behind why you presented that illustration is to really put the idea of the power of wetware that we just do not have in our current technological landscape as it relates to computers and chips and engineering.

Like wetware, biology, the promise of synthetic biology is that the wetware can become orders of magnitude more powerful than what we have today.

1 should be apparent already and then there's something that synthetic biology uniquely unlocks.

So the 1 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.

My phone does not organize matter from the environment and grow off and bud another phone.

We've got reproducing machines in a Johnny von Neumann sense.

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.

Alright, so let's just dive into that for a second.

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.

And so that that can be represented itself in zeros and ones.

So sequencing of DNA lets me go from atoms of a piece of DNA to bits.

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

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, right?

And then we can redesign it in the bit layer.

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 TAA, TA, CGA, CTC, ACT, ATA, GG, AGA,

Oh, that's a promoter that turns on gene expression.

By the way, you can memorize sequences by making them your login passwords.

It's a functional sequence that gets genes expressed.

Atoms to bits with reading, bits to atoms with synthesis.

So those 2 technologies, DNA sequencing and DNA synthesis, make genetic material and genetic information interconvertible.

And let us take the superpower of the internet, which is to move information around in space-time by decoupling and recoupling it, and combine it with the superpower of biology, 1 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.

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 all of a sudden now, synthetic biology, rabbit hole, hopefully you're seeing is like crazy interesting.

We're gonna take the superpower of the internet, decoupling information from space time, 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 de-globalization, we can go for that, and so on and so forth.

I hope what listeners are starting to see is, like, first we have this read and write layer,

First we can read DNA, and That was a technology that we unlocked a number of decades ago.

Then we upload that information in bytes, in binary.

And we have that expressed in digital form.

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, and then we have another technology that actually writes that right DNA to actually manifest in actual DNA creation.

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

I want to backfill something just in case it helps people ponder.

However, that 1D printer programs the molecular machinery of cells, including ribosomes, that get you to 3 dimensions.

So I've got a 1D printer that programs, actually a 3 and 4 dimensional with time, you know, manufacturing platform.

We've got a 1D printer hidden in DNA synthesis.

The next level up is cells and ecosystems and, you know, what's beyond that is microscopic and macroscopic manufacturing.

You know, So what can you do with a cell right and 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 it oftentimes a description of what it is.

Sugar loving fungus, Saccharomyces, and then cerevisiae, beer.

So normally you'd take, it's a cell, it's a reproducing wetware machine, it's like 4 to 8 microns in diameter.

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

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

By the way, you know what's really cool about plants?

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.

And so because plants can't run away from insects or mammals Over evolutionary time scales, they've developed defenses and modulators of insects and mammals, which are these crazy chemicals we find in plants.

Right, and so what you're saying there is that they have been rid of the opportunity of running away.

So, as a reaction of that, they have instead created an explosion of other compounds and proteins that we can now upload and learn from and those are our building blocks.

Well, an inspiration of chemistry basically, like a whole molecular keyboard that can be used to, you know, you ingest certain plant substances, they change how you feel and your behavior.

But so, we can take inspiration from the chemicals found in plants, but how would we get those chemicals?

So, of course there's an illegal market for poppies, but if you need a pain medicine, it's very properly derived and supplied, how does that get to you?

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.

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.

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