SPEAKER_00 0:08

Welcome to a fresh face in hell. I'm your host, Jonathan Evans. Every week we talk to someone new and interesting, somebody intellectually curious, somebody who will hopefully renew our faith in this cold, cool world we live in. A fresh face in hell. As you know, sometimes on this podcast, when I'm not interviewing musicians or authors or cops, I like to get in over my head on a subject that I don't really know much about. Um, and today that would be synthetic biology. We've talked about uh CRISPR in the past episode with Kevin Davies, but beyond that, we've never really taken a deep dive into the subject. Ergo, this week's episode could easily be called synthetic biology for dummies. Um I'm the dummy, but I'm a curious dummy. Uh, and today's guest, Andrew Hessel, is a pioneer in synthetic biology, a futurist, microbiologist, and geneticist. He's also an inventor and entrepreneur, which by my count gives him one more job than me, old Johnny Five jobs. Please welcome to this week's Fresh Face in Hell, Andrew Hessel. Andrew, thanks for joining us.

SPEAKER_01 1:18

Hey, nice to uh be here, Jonathan. Thank you for the invitation.

SPEAKER_00 1:22

I want to thank uh Andrew for being five minutes early. That's a rarity. Usually we're waiting around. It's like 1.07 and we're texting the guests. So thank you for that. Um, let us start broadly for our listeners and drill down into some of the fascinating specifics of your work. Um, can we start this very can you start with the Human Genome Project and then tell us how and why you founded the Human Genome Project Right? That's W-R-I-T-E.

SPEAKER_01 1:46

Yeah, so early in my career, I was really um uh I was doing bacterial genomics. So basically uh organ learning how to sequence and understand uh a bacterial genome. Think of bacteria as just some of the simplest cellular life on this planet. Uh concurrently, uh other scientists were were had launched and were organizing the Human Genome Project, an effort to read the human genome. What I love about that project was it was conceived and funded and launched five years before we'd even sequenced the first bacterium. We're really human-centric in our thinking about biology. But that being said, uh I worked with a pharmaceutical company that was a partner to the commercial group uh working to sequence the human genome, Solarogenomics. Uh, I the whole period of of scientists racing to sequence the human genome was a very exciting time. And that wrapped up uh the draft was done in 2000, the the project was done in 2003, essentially, all all uh all the eyes dotted, etc. Um, so after that, I moved from reading genomes into aspiring to write genomes. Uh and I started exploring that technology for um uh post-2003. Uh in 2010, Craig Venter, uh recently deceased, uh, had synthesized the first microbial genome, work that is uh was incredibly insightful in pioneering for the day. Um I ended up working to make some viral genomes, just uh uh viruses that infect bacteria. They're called phage. I started doing that in uh in 2014. Um, and uh today in 2015, I was able to bring scientists together uh to really start scoping out the idea of writing the human genome. Again, since we'd sequenced, you know, we're we're working to sequence the human genome before we'd even done a bacteria. I thought we were a little late to the game to kind of propose synthesizing a human genome because we'd already made the first bacteria. Um, and and really I've been the chairman for that project uh ever since. And um it's I I'll just say this we were a little early to the table with proposing to synthesize the human genome. But um 10 years on from launch, now the whole field of of being able of synthetic genomics, being able to build genomes from scratch is is starting to get some real traction. It's exciting.

SPEAKER_00 4:41

Okay, so I know we're off to a good start because it's already going way over my head. So I know I'm gonna learn today. That's my that's always my goal. So when you talk about synthesizing, when you talk about, when you talk about um um uh designing these genomes, is this something you simulate first? I mean, on paper, on a computer program, or are you are we talking about people with a petri dish here? I mean, I know I I sound naive here, but like really, how does this work?

SPEAKER_01 5:05

No, so so here's the beautiful thing. Every every organism on earth essentially has a program. Yeah, um, that is its genome. It is the genetic instructions required to build the organism and operate the organism and ultimately allow the organism to reproduce. Um that's the operating system. That's the operating system. And every single organism, from a bacteria to every plant, every virus, every every every animal, every organism has a genome, a full set of instructions on how to make and operate that organism. So um when you're when you're moving from, you know, we'd spent many years developing the technology to read or sequence a genome. Um, and and that's literally inspect the code, read the code and inspect the code. And with you apply the right computer software, you can understand that code. You can annotate it and figure out what it does.

SPEAKER_00 6:10

And this is kind of where CRISPR comes in, right?

SPEAKER_01 6:12

Well, no, no, CRISPR's CRISPR is separate. So right now I'm just talking about reading the code and analyzing the code. When you start moving into synthetic genomics or synthetic biology, or what I increasingly call digital biology, now you're starting to take that knowledge from reading a genome and understanding it, and now you're trying to write that genome. You're trying to build it from scratch, from you're trying to assemble the genetic instructions from scratch to be able to build either a component of that organism, or indeed, if you write the whole genome, the organism itself. So, so basically it's like it's like reading and writing software, except instead of working with electronic bits, you're working with the molecular bases of DNA and RNA that encode the the operating system for a biological organism.

SPEAKER_00 7:14

It's nuts. I feel like as a species, just the last 10 years, I mean, after literally centuries, eons of sort of debate debating nature versus nurture, if when you're a parent, you start to really go, wait a minute. I I got three kids, and so I've raised them in the same environment, the same culture, the same, they have the same experiences. They all do the same thing on their seventh birthday. Like I'm looking for a consistency in the child rearing and the culture that they're raised around and the traditions and all this structure, and they turn out completely different. You know what I mean? That none of them look like me, they don't act like each other. I don't, I just feel like it's as a whole species, we're starting to realize that the nature versus nurture argument is really starting to you know to to to lean towards this program you're talking talking about. Like we're worried about our kids stunting our growth. Well, it turns out if it's genetically coded that he's gonna be tall, he's gonna be tall, right? Like, I mean, he can eat one cheeseburger a day, and he's probably still gonna be short of actual starvation. That's genetically coded, right?

SPEAKER_01 8:16

Well, it's a little more complex. You're starting from the the top down, so to speak. You're starting with humans, which are unique species, even among animals, right? Like we are we are completely unique, and we're arguably the most complicated of all living creatures. Um, and and I like to say that when you look at a complex genome like the human genome, um, it's not a program, it's more like a recipe. And if you give the same recipe to 10 different cooks, uh, you are going to get 10 different meals. Like they're all gonna be similar but different, right? So, so it's more of a recipe. There's a when whenever you're talking about multicellularity, and and we are we consist of about 40 trillion cells, give or take. That's like 40 trillion little computers that have to work together. And independently, they each have a genome, they each have their own program, but they have to cooperate to build a body, a multicellular body. It's so much different. It's so much different when you work from the bottom up. If you work with a single-celled organism like a bacterium, and bacteria have been on this planet for billions of years, billions, but they are the they are among the simplest cells. Those they're the program, the genome is is is much more like a program. It's not so much a recipe. One bacterium is very much like the other. And if you were to build a bacterial genome from scratch, you it'll basically operate like the wild type, the natural bacterium, because uh, because you their their genome works much more like a program than a recipe.

SPEAKER_00 10:03

There's not as many variables, basically.

SPEAKER_01 10:05

There's not as many variables, it's a single cell, it doesn't have to cooperate with you know with with trillions of other cells to produce tissues and organs and uh and you know and all the complex systems that are in a in a multicellular animal.

SPEAKER_00 10:22

So, how far along are we now? I mean, uh and why is it important for the public to understand the distinction between gene editing and synthetic biology?

SPEAKER_01 10:30

And I'll I'll make that distinction in a second. Why is this important? Um uh biology is the only technology humans didn't create. It's the technology that created us, right? Like we it's it's existed before, you know, long before we got here. And it and I like to say this is a living world. There is so much life on this planet, and and we know, you know, that we're a pretty unique planet. Um, so right away, life is incredibly important. Um, we've been reverse engineering life, taking it apart, dissecting it, you know, collecting it and dissecting it. You know, the early expeditions was just were just to go out and find animals in different continents and put a pin in them, essentially, and put them in natural history museums. And and we we explored the diversity of life on this planet. Um, and and we didn't just collect it and put in museums, we dissected it. We literally looked inside, we studied the bodies and shapes and correlations. And today we do that at a molecular level. Um, and it is really exciting. Plus, now with DNA sequencing and other technologies, we can explore the actual code that made that organism, which is super cool. So we've gotten really, really good at reverse engineering life, right? And we also developed tools to start to manipulate that genetic code. Because if you change the code, you change the organism, right? Like that's CRISPR. I finally got it right. Okay. So, so yeah, and and before CRISPR, we were doing other things like moving blocks of code and inserting it into bacteria, for example, like like insulin, which we use to treat diabetics. We took code from humans and moved it into the E. coli bacterium, a you know, a single-celled organism that grows really quickly. And we we essentially reprogrammed the bacterium to make human insulin. And that's how we treat diabetics, because we could not get enough insulin from natural sources to be able to satisfy the need for insulin in the world. We had to figure out how to genetically engineer an organism to produce it at scale, and CRISPR allows us to is another form of editing existing DNA.

SPEAKER_00 13:02

So I have a dear friend with Deshan muscular dystrophy, and they can treat him with steroids and so forth and sort of keep his degeneration in check a little bit, but they cannot, they've not figured out how to make the bones produce dystrophin yet. So but we can make something, we can make the body create insulin now. Why is dystrophin do you why would dystrophin be so much harder?

SPEAKER_01 13:30

Uh, you know, trying to do any genetic repair or adjustment of of a full grown organism like ourselves, like when like we're look, we're essentially adults at 18, right? Like that's as much of our you know, biological development that we're gonna get. We peak we basically peak at 25. And but trying to go and do a repair on call it 40 trillion cells in a very accurate and precise way is really hard. Imagine if you had to go out and visit 40 trillion individual computers and and add a patch, right?

SPEAKER_00 14:12

Like so you're saying if you could find the gene within the genome, if you could find the place where it wasn't producing dystrophin beforehand, you're gonna be more likely to to head off the disease. Well, if you if you can Whereas if you have a full-grown person and you're just trying to inject them with something, uh I know I'm well I know. I really want to understand.

SPEAKER_01 14:39

Um so look, if if you've if you know what the the genetic deficiency is that causes an illness, uh it doesn't matter what illness it is, but if you know what it is, remember we all start as a single cell, you know, like we start as an egg cell that's fertilized by dad, and we start to grow and divide into an adult. If you know what uh if you know that there is a deficiency, and today we can find that through our sequencing technology, then then you can basically say, okay, that embryo is defective, don't turn it into a human being.

SPEAKER_00 15:19

Uh that technology, but you can't work on the embryo. You can't you can't change the sequencing of the embryo.

SPEAKER_01 15:26

It has to be uh so now you're talking about doing genetic surgery on an embryo, which is possible, but but the very first time that was demonstrated uh in practice, and it's still not verified because it happened in China, was the Chinese scientist in 2018 that basically did genetic surgery on an embryo uh uh to make it HIV resistant. And it's never been scientifically validated or verified. It was a huge big deal at the time. Um now moving on, you know, literally eight years later, there are there's at least one company, Origin Genomics, that was founded in the last year to start to say, hey, look, if there are embryos that that are damaged, we we want to be able to do that genetic surgery to fix it right then and there. Um, like and essentially rescuing embryos so we don't have to abort them. That's huge. But once you know, once there is a genetic anomaly, you know, in that embryo and it grows into the baby and eventually the adult, now there's 40 trillion cells that potentially you have to repair. Jesus. And and we just today we do that by by a gene therapy. And some diseases, you don't have to treat all 40 trillion cells, you can treat a subset of cells, but you still have to make a uh usually it's a virus that carries a uh a program, a genetic construct that is going to repair any cell that it infects. And but it is a huge challenge. You have to understand the exact genetic deficiency, you have to write a new program that is a genetic therapy, you have to package it in a virus particle that will infect the right cells and only the right cells, and then it has to replace the damaged genetic code without causing more damage, right? So it is a it is so much harder to do patches and repairs and diagnostics on a living system than a computer system, but the processes themselves have analogs, right? So we're learning and we're learning quickly. And between better diagnostics and better therapeutics, um, uh, you know, right down to the single cell level, um, I I believe that we are just in, you know, uh, you know, the most amazing time ever when it comes to human health.

SPEAKER_00 18:15

Um and that's just going to accelerate.

SPEAKER_01 18:17

Yes.

SPEAKER_00 18:18

It's like culture, scientific thought accelerates.

SPEAKER_01 18:23

And it will accelerate faster than most people recognize, because at the end of the day, you don't have to build the machinery, you just have to write the code, right? Um, so uh I I think we're we're starting to see this play out in more and more diseases. And I'll give you an example. Last year there was a baby, baby KJ Muldoon, that was born with a metabolic deficiency. Like they something was wrong with their metabolism, and they and it needed a genetic therapy to to make this baby healthy. And and they diagnosed this baby uh at at you know by sequencing in the first week of that baby's life. And they designed and built a personalized genetic therapy to repair that deficiency uh uh in within six months. And they started to deliver that genetic therapy over the coming months, infecting the right cells to create this repair. And by 10 months, the baby was at home and and doing well. And we'll have to follow baby KJ's story, you know, for for from you know, from further, but but that was huge. Like that was six months from diagnosis to personalized genetic therapy to repair. And that's an anecdotal example. But the core technologies that allowed us to do that type of work are just accelerating. And I want to be clear, I'm not a medical doctor, I don't work on humans, but I love this technology that allows us to program biology with more and more precision. And I work bottom-up. Like I want to see this technology be used in in much the same way that computers, you know. Um, there were two main camps in computers in the early days. There was the IBMs and big computer systems, you know, selling to institutions and governments and and companies. And then there was the bottom-up, you know, computers, the personal computers that started to emerge in in the late 1970s and and ultimately, you know, changed the world. Um, I like bottom-up, not top-down. I I'm done with big pharma and big organizations and how slowly they move. They do really important work, but it's not scalable, so to speak. Um, but I love the fact that biology is becoming programmable and the tools are becoming more accessible and inexpensive for uh for a growing number of people that want to explore programming biology. And I think we're on the cusp of unlocking a huge amount of biological creativity, you know, which will translate into better medicines, et cetera.

SPEAKER_00 21:13

You're kind of leading me into what was going to be my next question. Like, I can actually envision uh a ton of promising possibilities for synthetic biology. And uh, I I want to devote a lot of time to futurism going forward here. But here's the thing that scares the hell and hell out of me about this technology is I I can see right away how this technology could help with diabetes, with fertility fertility, or hundreds of other beneficial uses in the medical field. But it's an ethical minefield, right? I mean, history tells us that new technologies like this can be used by governments, uh, corporations, et cetera, toward nefarious ends. Does the existence of this technology scare you in that way?

SPEAKER_01 21:52

Oh, yeah. Well, every technology, uh every technology, fire on up, has both a positive Positive and negative application. At the end of the day, it's always about uh the human intention, how it's being used. What I know is 99.99% of us will use technologies in a positive way. Like you know, we'll just we'll either be consumers of the technology, or if we do our developers, we'll do it for something positive. But yeah, every technology has will uh has a small population of people that will abuse it. Uh, we know that.

SPEAKER_00 22:35

Uh and that small population tends to be kind of towards the top of the hierarchy. That's sort of the problem here.

SPEAKER_01 22:41

Not necessarily. And I don't think it's the case so much with biology. Um look, in general, from top down, governments on down, very few there there very quickly we made uh international treaties against the use of bio as as weapons, in part because we felt it was difficult to control, it was difficult to train people. And and once biology, once you release it, there's no recall mechanism. Um, so it's a lot different than making a bomb or a balloon, you know, like it's a very different technology.

SPEAKER_00 23:17

Um, you know, and as I was gonna ask, how do we responsibly govern a technology like this? But what you're telling me is we already kind of are.

SPEAKER_02 23:26

Well, we we've we've always thought about it.

SPEAKER_01 23:29

The uh perhaps the thing that's changing is the the technology is becoming more accessible. And as you know, as it expands beyond professional communities or government communities or even corporations, now it starts to disseminate. And now you get a lot more um uh intentions brought to the table with the programmers, and some of them may be political, some of them may be religious, some of them might be I just want to see if I can break it. Some people might want to find the edge cases. It's uh we saw this with computing. So, my core thesis, Jonathan, is that everything that uh has happened and will happen in digital biology, I don't call it just synthetic anymore. It's digital. Okay. Um, has already happened in digital computing. And digital computing, we've got the whole history for. We've got all the patents, all the records, all the stories, all the inventors, but but it it followed a clear path. There were academics and and groups, very specialized groups, that built the first computers, that built the first networks, and and started to build, you know, the very first ARPANET, for example. But as this started to expand and more people came to computing, um, we started to get problems. Like again, the PC revolution that started in the late 70s and started to grow in the 1980s. Well, it wasn't too long. I think it was the 1984-ish. I the first uh early 1980s, we got the first instance of the first virus, you know, computer virus. And it wasn't destructive or anything. It was just, it was, it was kind of sweet in some ways. It was just some guy trying to protect his software from being passed around on floppy disk saying, hey, uh, if you've got this, like, you know, please pay me. Um, but anyway, the the the point is we started to see the first we started to see the first, you know, we started to see the first malicious viruses, we started to see the first network hacks, we started to see the first, you know, uh by uh, you know, cyber errors where you know, where someone made a coding mistake and took down a big chunk of of the internet, for example. So now we realized, oh, we have the potential for these cyber pathogens and and malicious use. Now we need a cyber defense system. And ever since that happened, kind of like an immune system. And and that continues to the day. Now our biology already has an immune system, you know. Like if we didn't have an immune system, we'd be dead in days, right? Like we already have an immune system, but because we're learning more and more about biology, uh, there's there we can we can hack the immune system too. HIV did this naturally, you know, they that virus attacks the immune cells, you know. So, you know, even nature can find a way. But but uh, you know, I think it's just really important. So do I do I have worries about this? Yeah, uh, but I only personally, personally, and it's not for everybody, um, I I mainly worry about viruses because I I I know they're relatively easy to program. We know that they can spread very quickly, they're invisible, they're invisible, they're smaller. You need an electron microscope to really see them. And and we know that they can uh some of them are harmless, but some of them can be very deadly. So, so we we need to think about um viral defenses, both for natural viruses, uh the flus, you know, the colds, Ebola, whatever, natural viruses as well as engineered viruses. And and that is going to mean putting in a new layer of security with the with the tools of digital biology. We should be able to stop anything that people are trying to program long before it ever gets made. But we also need real-world detection and remediation because Mother Nature is making this stuff all the time, new combinations, and there's the potential for people to breed or design um, you know, agents we've never seen before. So so we see that.

SPEAKER_00 27:50

And I don't trust, I don't trust the government not to do that.

SPEAKER_01 27:54

Like, I mean, we've got all my shorts my short speaking point on this, Jonathan, is um look, cybersecurity is a $250 billion industry today, annual revenue, because we have to protect our electronic networks. That's a good point. Cyber, you know, biosecurity will become an industry.

SPEAKER_00 28:16

Well, and I'm certainly it's a growth industry after you know, after COVID, right?

SPEAKER_01 28:21

Not enough of a growth industry. Like I I want to be clear, like there's there's certainly new efforts around biosecurity post-COVID, but do you have a um you know, do you do you have the ability to sense and detect and identify viruses in your home? I don't.

SPEAKER_00 28:38

Um and and just one, and it's the things like you know, three and a half years over, you know, the expired, but yeah, I mean, I guess well, that's just it.

SPEAKER_01 28:47

They were these were one-off swabs, right? Right. Uh what if you had a flu? The COVID test will give you a negative and you don't know what you've got. So I've I've been championing the idea of a sequencer not much bigger than a phone, that will essentially be a universal swab. You you you start feeling sick, swab your nose. That's usually the the way you get a new virus that's circulating. You breathe it in. So you swab your nose and you sequence it, and you can identify whether it's cold or flu or RSV or COVID or something brand new that um you know that is starting to circulate. So I think that's kind of that first line of defense that every person needs in their medicine chest beside the band-aids and the thermometer that just doesn't exist yet. That will be a huge, you know, a huge layer to biosecurity.

SPEAKER_00 29:43

Um that's interesting. It reminds me of like how new cars, of which I have none, my newest cars are 2005. But the new cars have like a computer in them that can diagnose, like you know, a tech just gets in there and without tearing the engine apart or, you know, like even peering in there, they can diagnose where the problem is. Yep. Like because so it's so it's sort of like that.

SPEAKER_01 30:04

Yeah, yeah. I think we all need that. Um, you know, I well, that's it.

SPEAKER_00 30:07

That's a hopeful idea for technology.

SPEAKER_01 30:09

I think our smoke detectors will become biodetectors as they get more powerful. Like I've got a nest, you know, uh smoke detector, but it you know, it does smoke and carbon monoxide and other things. And I think eventually it'll just detect everything that could, you know. My mom's cooking.

SPEAKER_00 30:27

So I gotta ask what implications emerge when therapies shift from like treating disease to enhancing human abilities? Because we know it's gonna happen. And the first one that comes to mind for me is access, which could come down to economics, will come down to economics most likely. The billionaires could uh engineer super five uh you know, superpowers basically, while the rest of us just kind of wallow in this, you know, shallow gene pool, right? I mean, like, what's to stop that from happening?

SPEAKER_01 30:52

Oh, well, you know, what's don't knock don't knock the wealthy. Here's why. Like, look, we wouldn't have cheap cell phones if someone hadn't bought that big brick that you know was used in the movie Wall Street, like you know, the big Motorola. Uh new technologies are always expensive because they they're expensive to make prototypes, they're they're expensive to start getting into the market until you scale production. Um, but you know, it tends to be the wealthy folks and folks that have money to burn that go out and play with these technologies. And if they catch on, then they become cheap enough for everyone. Bio is a little different because biology self-assembles, it's not manufactured. Um, you know, so so there the economics are a little bit different. I always I always ask people, like, how much did your last flu cost you? Right? You know, like nothing. It infected you and it made its viral particles and made you sick, but it didn't cost you anything. Um and loss of labor, I mean work well cost you some productivity, but it didn't cost you money directly to make that flu, right? But if I was trying to engineer that virus, it comes down to the cost of making the virus genome. So, what I'm saying is the cost of making a virus to infect someone and cause them to suffer or die is about the same as making a virus to do something really, really positive, like do a gene therapy. So it can the core technology, it's kind of like computer software. You know, like once you buy a laptop, you can go and make a program that you can sell, you know, a billion copies of to kids to go do something useful, or you can write a malicious code to take down an organization. But the the real cost is just the laptop. So as the cost drops, we have this dual, you know, this dual use problem. Most people are going to use it for something productive. Um, and it's not going to be that expensive. In fact, we can arguably start to play with the technology once it becomes cheap enough, you know, to that we can afford it and kind of, you know, we can all afford it and play with it. But we have a bigger security problem because now a lot more people are experimenting with the technology. So right now we're a little imbalanced, like in the early days of computing. Lots of people started to buy PCs, started to get online, started to play with this stuff, and we didn't have the right defenses. And and we're kind of in that boat. But we we don't have to learn these lessons again. We we just have to balance the equation properly. As bioengineering becomes more accessible, it shouldn't get that much more expensive. There'll be a lot of competition, but we also have to make sure that we invest properly in biosecurity.

SPEAKER_00 33:44

So China's probably way ahead of us on the biosynthetic front, right? I mean, at this point, they seem to be in almost every other way infrastructurally and technologically ahead of us. Is that the case? I mean, you were talking something about 2018. Yes, it wasn't proven. I mean, there's no demonstrable proof. It was just a paper or whatever, but like that was eight years ago.

SPEAKER_01 34:03

Yeah, well, we have the technology to do it. The problem is, um uh so so here's the way I look at it. Uh, number one, you get more bang for the buck in China, right? Like uh you you put a you put a million dollars into processes in China, salaries are lower, infrastructure is lower, regulation is lower, you get more bang for the buck just dollar-wise. But there are two other big um, two other big factors. In China, there's uh a political run by engineers, they plan things out in five years, ten years, twenty-year increments. Like they have a plan that they're trying to stick to. And biotechnology is a systematic part of that plan. So there is a political tailwind saying, go do this, go do this, um, which is great. We don't have that in the United States, we don't have in Canada, we uh we don't have in Europe. There's no systematic push to make this a core technology that we're gonna advance, you know. Um it's very ad hoc. We know you got some application people are developing. The other big the another one is the US is particularly litigious. If you go and hurt anyone or do anything new, you're gonna get sued. And so there's always a legal aspect, and that's a huge break on in some innovation if it causes anyone any harm, discomfort, whatever. That's another factor that's not as big in China as it is in the UN in the US. And then there's another headwind, which is um, you know, again, this is a technology, biotechnology life is something that many people consider divine technology. Uh, as a geneticist, every, you know, people would say I was playing God. Um, you know, and and there is a religious headwind that slows down the innovation, particularly because the um, you know, the politics in the US is is very emotional, not always rational, you know. Um, and and so the combined that makes a a structural challenge for the US to compete as quickly as China. So, so that being said, um, you start unlocking these technologies and giving it to millions of Americans. Um uh Americans are hugely creative and they tend to um they they don't tend to ask permission. They tend to apologize after and and the when the dust settles. Um, and and so I think that the best thing we can do is make this technology accessible to a new generation, the younger folks coming in, uh, and we we kind of set some guardrails, but but let them explore and play and create and uh and and make stuff that people want. And I I think we can absolutely compete with anything China can do, but uh it's just understanding the structural differences between the nations.

SPEAKER_00 36:58

So, yeah, I was reading somewhere, or maybe we were talking about it here on the show. I don't remember, how scientific progress often gets wasted on more uh like novel concerns because the researchers and scientists follow the grant money and the funding funding. And sometimes these I mean, I've heard scientists interviewed where they're saying, just admitting basically, yes, I had to get the funding to do this thing that's really not benefiting the world. It's really pretty trivial, it's really kind of stupid, and I'm using all this human and scientific potential toward this thing just because uh, like some top-down mandate from the whoever granted the money. I mean, what can you tell me about this dynamic in in the field we're talking about? In uh uh, you know, in in in bi biosynthetics.

SPEAKER_01 37:44

So when I was an academic or in the academic system, um, you know, we'd write a grant to get the money, uh, and we do what we wrote the grant for, but but you know, we'd also take a huge chunk of that money and go do the stuff we actually want to do.

SPEAKER_00 37:59

Uh that's that's insightful.

SPEAKER_01 38:03

Well, that was the way it worked back, you know, 30 years ago. Today, the the knowledge cycles are a little different, and and the and sometimes the requirements, you know, around reporting what you did with the money are a little more stringent. But, you know, again, just with this new administration, funding has all been destroyed. I'm not part of that system anymore. Everything's being shaken up. What I what I ended up gravitating toward uh was the entrepreneurial space. And this is where I loved groups like like Y Combinator, for example, and the various accelerators and incubators that would help people take an idea and move it towards application. I I really enjoyed that space because there you could sit down with a napkin and a couple of friends and say, hey, let's go build something by uh an enzyme, for example, that turns carbon into diamond. Just a silly example, but but not inconceivable. And you could come up with a plan for that, and and you got a couple of people that know how to do protein engineering, and you got a guy that knows a little bit about business, whatever. It doesn't matter. You you you build your team, all these incredible people, men and women, you get them together, you tell a story, and you can go to a VC or an incubator or an accelerator, and they'll write you a check for more than what you could get from an NIH grant.

SPEAKER_02 39:27

Um, so so that's huge. And what isn't that contingent?

SPEAKER_00 39:32

I mean, are they buying your exact idea or are they saying, I really like where you're going with this, the technology? What if we used it for something a little like this? Well, wouldn't it do that? Wouldn't it do that? If I'm writing you this check, couldn't we take what you've discovered? You're the technology, and couldn't we just kind of I mean, because that's the thing about entrepreneurship is like what regulates it? You know, that's what scares me is like in China you've described a system that's like very infrastructurally sound that they've they've put they've got these building blocks in order, those are top the top down endings, but they're regulated and entrepreneurial in the entrepreneurial space. How regulated is it really? Oh, it's I mean we've got regulated laws, but you know, but you know what?

SPEAKER_01 40:16

I love about the entrepreneurial space is you sell an idea, and maybe you have a prototype, maybe like more and more you can build a prototype even before you go and raise money. But you know, for the most part, you had an idea and you sold it, and and a few people that you know the team was really important, and someone would write you a check, and then you start doing it and you learn by doing really fast. Right.

SPEAKER_00 40:40

So now that doesn't scare me because you have the prototype, right? So it's right from the impetus to the product. Whereas I'm saying it's more like intellectual property when you're dealing with this synthetic biological biological concept, and somebody could go, Oh, well, if you could do that, couldn't you also do this? I got the checkbook here.

SPEAKER_01 40:57

You know what I'm saying? Yeah, but yeah, and everyone's you know, the thing I love about the entrepreneurial space is we're all chasing, you know, we're chasing trying to make money, right? Like that's uh like that that I I actually understand. I and and it's a really easy metric. If your company doesn't raise money, uh eventually you're gonna collapse and fail. And well, that's uh that didn't work. But you know, if your idea didn't pan out um as you're working on this, as you start doing it, well, you pivot and you adjust. That's what I love about that. You can't really adjust with the grant system. You write a grant and say you're gonna go do this for the NIH, it's really hard to pivot.

SPEAKER_00 41:37

You know, you might be doing a side project with some of the money, um, but it's really hard to talk about you discover something during while you're trying to execute that thing, you might come up with a more exciting uh prob or possibility, and you're not able to follow it because you're still stuck within the yeah, you have to deliver what you said.

SPEAKER_01 41:54

And again, the grant system, and again, I'm not part of this every day. There's people that could speak much more knowledgeably about this, but with grants, they usually have, you know, they're usually awarded once a year, if that. And and so you've got to get all your ducks in a row. You sit all, you submit all this stuff. If you if you get the money, that's great. It's kind of a block. Um, but but you know, with a VC, I go to, you know, the thing I love about the VC environment is I go and pitch something to VCX, and you know, they go, Yeah, we pass, but they'll tell you why they pass, you know, like uh we don't like your team or this sucks, or your idea doesn't work, or it's been tried before. And and so you go back to your Starbucks and you work your plan, you do it again, you go to VCY, and and you just you know, you keep doing that until someone says yes. You like some of the entrepreneurial stories that you hear are, you know, they got a they tried 130 pitches with a different groups until someone finally said yes, and then it worked, right? Like, so you don't get that opportunity in the academic system quite as much. And so, like the the systems are different and complementary. There's so many different paths to doing this, but what I love deeply is that biology is a becoming programmable, too, the the creative space is huge. You might just want to work on a protein, you might want to reprogram a bug to make something useful like insulin. You might want to go and rebuild a genome from scratch and make an organism print on demand. You might have some wild ass new idea that you know that is now possible because you have full control over programming the DNA or RNA of the organism. Uh, like that to me is just so exciting. And we're we're in the earliest days of this. And the only template, the only model, the only experience that I can tap into, even to guide you know, my thinking about the future computing, right? Is computing, which is huge and incredibly fun. Uh if you're in the Bay Area, go visit the you know, the the the the of computing museum like it is amazing just because you it all played out in our lifetimes you know like it's all happened in the last hundred years so it's been I can only imagine you know how the core technologies that have come into play since we read the first human genome and started sequencing the first organisms and and started building the first enzymes and and and and metabolic systems and and bacteria and virus how this is going to play out over the next century but I I I feel in my heart and in everything I've seen in in in my life that it's going to be huge and and positive net positive like the world around us today has been built on technologies innovations processes that were huge most of them chemical right you know the oil industry sucking goop out of the ground refining it pul polymerizing it into plastics uh turning it into fuels and other compounds like the the huge industry but but ultimately unsustainable you can't keep pulling goop out of the ground every time you drill a hole we could but we've built an apparatus that doesn't I mean like look in 1970 a guy created a uh an internal combustion engine with a 455 engine that could get 180 miles per gallon and he discovered it by accident he had uh the two the the fuel tube on his lawnmower had a leak in it or something like that he figured out a way to create a carburetor that used the fumes of the gas to combust so that the gas so we've known about these technologies the problem isn't I mean we we probably could have had the oil stores I think to have stretched uh uh two or three centuries longer and done less damage to the earth now but the apparatus that's been put in place to make the money has stopped it I mean we've already there are patents for these things that they're they're more fuel efficient so like a barrel of oil suddenly could go 50 times farther than it does but the apparatus in place by the people at the top of this like whatever you know capitalistic uh you know aren't gonna let that happen.

SPEAKER_00 46:17

That's what scares me about all this new technology. I love your excitement I love your take on bio uh futurism I just I always feel like every time we get close we get these tools technology gives us the tools to actually do more productive stuff. I mean I think the medical field is kind of the outlier here but in terms of the like industrial complex it usually gets used in in and misuse somebody tries to monopolize it or somebody tries to make it not work efficiently so that they can take dollars as long as they possibly can.

SPEAKER_01 46:49

So okay I'm done with my communist scree no worries but like look I can't verify your your example there with the fuels with the oil industry and the people damn it you just have to trust me. I read it in the I just have I have huge respect for the oil industry because I've worked with them in the past and it runs the world but there are better technologies that are cleaner and more sustainable and I look forward to transitioning some of our industries towards that.

SPEAKER_00 47:16

So I hope so I'm having to push back I like you Andrew but I got a push back already you're telling me don't be hard on rich people and you like the oil industry.

SPEAKER_01 47:25

Look in which people employ a lot of people too like I want to see things change but look we have eight billion people uh eight billion and and most of us if we're really entrepreneurial run a mom and pop shop maybe and you know like I I am fascinated by organizations that scale whether it's Walmart or SpaceX or it doesn't and everything in between like uh anytime you can build a system that that works and grows and is sustainable and and delivers products and services to people that help them um I I am I am man I'm blown away because I live in I live in largely theoretical space I work with microbial and molecular systems these are not these are these are systems that are almost invisible for people one because they don't know them and two because they can't see them and three we haven't there's no huge success story in digital biology yet it's too young a field it's building up a head of steam it's used as a tool by existing industries whether it's you know a pharma company a hospital like we're starting to move towards you know the the the technology of digital biology becoming useful but there is no so then can somebody I'm sorry to interrupt but I mean can we engineer a biological entity that could you know say reduce fluorocarbons in the atmosphere patch up the ozone cool the planet is anybody doing that with the technology yet I mean isn't that what we are starting to go that way the example that has emerged over the last few years is being able to engineer enzymes again proteins that can digest the plastics in plastic bottles and turn it back into monomers but that here's so that's pretty cool you can actually digest plastics we'll probably do the same for styrofoam we'll probably do the same for a lot of other toxic chemicals that we've put into the environment we can break it down faster by programming biology. The problem is the monomers of those products you know the stuff we build the plastic bottle from is so cheap. You know like turning it back into the monomer uh like the that's that's not the hard part the hard part is how do you how do you take that monomer and turn it into something useful to justify you know the the the essentially the reactors to break down the bottles right like it's really it's not an easy problem solving the end to end economic equations. And we're we're just starting with this technology Jonathan like we're we're we're in the first 20 years of it.

SPEAKER_00 50:12

Yeah I mean and that's exciting I just want for I just want to see it you I mean look I mean we're in trouble kind of you know what I mean like we need to start figuring some of this stuff out while we have the technology. It's like you know William Shatner said when he went up in Bezos's peanut rocket penis rocket and Jet Bezos is just like hey look at me I went up there I I did this and William Shatner's just like fucking bawling and he's like oh my God it's just this thin little membrane you know this realizing how delicate it is and like you know I I mean I don't whatever I I'm sure you're not a climate denier or whatever we're certainly uh there's certainly I I just want to make sure that's I mean like synthetic biology could clearly probably help us eradicate starvation but are we gonna how do we collectively make that happen instead of just like you said all these little camps I've got my idea I want to monetize that I'm a little boutique over here I've got the I've got the attention of these moneyed people in in Silicon Valley they'll give me money to do my little thing how do you how do you create a top mandate and says like fuck we got to fix this shit before you know before it's a 130 degrees in in you know Minnesota yeah no we're gonna learn all this as we go and like everything the rate of technology evolution is going faster right like right where we see accelerate for sure and it's accelerating every industry is accelerating now in some ways because of the compute architecture we put behind it I don't want to get into AI but AI is a huge accelerant sporting gasoline on every fire.

SPEAKER_01 51:43

But the thing that I always loved about biology is it self-assembles. You don't need to build a big factory you know like once you once you learn how to program it you can build the applications faster and faster and you might build them just for yourself. You might build them just to cure you know a single person's disease but the collectively the foundation of the technology gets powerful quickly and we saw that with computing and computing is arguably the one technology that just keeps on giving like ever since I got my first computer a VIC 20 uh back in 1980 early something like it has what sustained me has has kept you know things interesting has replaced just about every other you know industry and vertical that I've ever seen like we don't go to banks anymore.

SPEAKER_00 52:34

You know like we do online I mean I kind of like taking that I mean I we what do we lose when we you know we lose something when we convenience isn't the end all effect I love the fact that I can just book a flight by myself I love the fact that I can rent a car online I love like my life has become so convenient.

SPEAKER_01 52:54

I still get human interaction I just get to avoid the you know the transactional garbage and and yeah you know and and the the inefficiency that came with with just a lot of those transactions. It was slow the banks were only open certain hours blah blah blah I really believe that as we start to program more you camp in a motorhome don't you you camp in a motorhome aren't you camping for yeah you're you're a glamper I can tell 20 years ago 20 years ago I did that. Now I'm happy with a pup tent and I see I like your I like your motorhome behind you. But uh but I love no now I just travel with a backpack. I I was a digital nomad before there was a digital nomad but now honestly I got two kids you know and uh when you have kids the they're they're just a lot more overhead.

SPEAKER_00 53:48

So yes I know this this is why I'm Johnny five jobs I gotta write books I gotta make movies I got to do a podcast I got to teach but hey I'm a I'm I'm a happy guy I just don't sleep a lot um so I'm I'm mentally going down this list of humanities problems trying to think of hopeful outcomes for this technology because I I I really wanted to go in the direction of biofuturism with a sort of optimistic spin what are some others I'm missing here I I I mean it seems like most of it so far is concentrated on the medical field for obvious reasons that I you know we can you we can work with the human g genome to eradicate diseases or to head them off or but like what are some of the other ones I just keep thinking I keep coming back to environmental because that just feels like that's the clock is ticking or something.

SPEAKER_01 54:32

I I don't uh like the we're changing the environment I'm not gonna argue there but I I think that will tip and we'll start changing the environment in much more positive ways as these technologies become more diversified. So I'm not but I there doesn't seem to be much uh it just doesn't seem like anybody's like that worried about it yet like it it seems like it should be a little more of a high priority but like you'd think so but but um yeah I I I think you know the problem that we have is we our brains uh individually can't wrap around you you know the they're limited in what they can assimilate. We don't have that problem with the compute systems compute systems can have you hold huge amounts of information uh in in context windows so I'm not so worried uh uh about the environment in general I think if people start to take care of their local environment better then it scales um and and I think it all sorts out so um yeah but we can't control the weather I mean you know we can't so like um and but but the the effects of weather uh at least here in in the western world plays out in insurance right like like when you're when your home gets flooded uh uh you know there's an industry that starts to get upset the uh when your home burns you can't even get fire insurance in most parts of you know I live in California it's it's one of the big challenges so the so everything starts to adjust as as the various economic pressures play on us um like look there's in I'm a biologist there's no evolution without stress if everything is going hunk and dory nothing changes but it's when things get stressed when you're you're running out of food when you blah blah blah blah and there's many we are though that's the point I mean I just know no one's starving yet like starving is not a problem yet except in very few parts of the world are starving um uh and and if you don't have enough food I'm sorry we'll we'll try and get some too but like there's uh but you are a hard hearted son of a bitch no no no i've been to I've been to the slums man this all seems so convenient though like I think I can see your pool in the background you're an entrepreneur you're like eh not so worried about no one's starving around here I gotta play to I gotta oh man man I I I have been to some very poor places in the world i and I purposefully went there and the thing that surprised me one is it's hard to find a place where people are starving. I'm not saying that there aren't places and certainly um you know I've seen horrendous pictures but but even in the slums of Uganda that I visited and the favelas in Brazil people the food's generally been plentiful drink has often been plentiful um uh and surprisingly the last time I went to the Ugandan slums um everyone had a had a flip phone they didn't have smartphones but they had flip phones because they'd leapfrogged uh physical currency and they'd move to electronic transactions so so everyone had a phone which meant they had the ability to communicate um and so look I'm I'm I'm not running the world I'm I don't have all the answers but I'm really optimistic based on my own life experience and the stuff that I see happening in technologies and and creativity and again bio is my main focus that that we're not going to crash and burn we'll we'll grow and adapt and make things better what I would love to see is just more people cleaner tech um you know uh a lot more bottom up rather than the big monopolistic and governmental top down and um but but you said yourself you're sort of fascinated with business models that can do that. I mean you used Walmart as an example and Walmart's amazing Amazon is amazing SpaceX is amazing.

SPEAKER_00 58:32

But their employees not so much I mean you know I mean like you know most of their employees is can't afford health insurance or whatever. So like again it's like the story of like things being built on you said without rich people we wouldn't have these cellular phones and I say well without little kids working in uranium mines we wouldn't have these phones. You know what I'm saying?

SPEAKER_01 58:54

I'm just joking yeah okay no but I but I'm actually really straightforward like I I have to go and experience it and see with my eyes and I'm always fascinated by people that get stuff done like uh always because they're uh it is really hard to build anything uh given the you know how difficult the challenges of raising money having a great idea just putting yourself into things um uh solving all the legal and operational challenges I'm always amazed by folks that get stuff done and make things that people want um I keep wondering because this is in so many of the the early advances in this technology are are centered on the medical industry for reasons we've explored already but what happens when we can eradicate genetic disease in fertile infertility prolong human life and then the global population just grows and grows and grows how do how do these technologies how do we use them to balance out our limited resources? Yeah we do have limited resources if we keep using them the way we're using them today I see the potential for a lot more abundance I see the potential for a lot more efficiency um uh if you look at the current projections of human population we peak in about 25 years and then it declines um I think that's kind of sad and defeatus actually I think we could probably have a lot more people if we just learned how to you know be a little more equitable uh and built technologies that are cleaner and more sustainable. So uh it'll it'll be interesting to see how it plays out because again bio is one of the most you know the the two technologies right now well three that are really profound and I don't think we know how they're all going to fit together and the doors they'll open up. One, we've built artificial brains, brains that are more powerful than our own, right? Like that's huge. Another one is we're learning how to program biology, whether it's medicine or food. Biology is what runs the world right like you know we we eat biology multiple times a day we we need biology to be healthy. We biology runs all the other ecosystems and we're starting to learn these really powerful processes. And the third one which we don't talk about as much is just automation. Like the reason why we can churn out cars as fast as we do is there's just robots working 24 hours a day. So those three things together like you know is is are massive and we're starting to electrify which is you know cleaner energy. But I I'm I'm hugely optimistic that the combination of those things uh put together uh solves a huge number of issues over this over the you know this century uh and I don't know what it'll look like but I hope it gets to the point where we realize man um you know we don't have to stop having kids because I I I I if I kids have been the best part of my life honestly I've I've programmed oh yeah you know yeah absolutely but but kids are amazing and and people are afraid to have kids now because they become so expensive and the overheads are so high I'd love to fix some of that we we worry about the world that they're going to inherit well let's fix that let's make a better world um uh well that's what I'm saying so we're on the same page there okay but yeah I don't know I I'm just a lot more worried than you I guess I I don't know where I don't know where the optimism comes from I I've just I've yet to see like I don't we haven't got to the choice we haven't got to the point with AI say like I'm watching that the the whatever Project Hail Mary last night I couldn't get through it I fell I fallen asleep three times okay I almost got through it and I'm thinking okay now I'm seeing AI is pretty cool here because this guy has no fucking idea what he's doing he doesn't know how to run this ship all he has to do is ask the ship and it tells him what to do.

SPEAKER_00 1:02:43

It gives him a protocol like he's and I'm like okay now I'm seeing artificial intelligence do something like it's gonna it can save humanity when it gets to that point, right? Like this guy could basically be a janitor up in space and just say hey spaceship what do I do? You know I'm gonna crash into that planet. Okay so now I see it's helping but like we're not there. I don't feel like we ever get there with our technologies before somebody just kind of stops it and says let's slow that roll and milk as much money out of it as we can before we this is a thing I struggle with because I'm I'm I'm I'm a progressive person in every single way right like except about baseball then I'm conservative but politically correct I'm kind of I'm kind of conservative about technology. Like I just the fact that it accelerates so fast is like makes me want to slow it down right because we have a natural sort of equilibrium and relationship with technology and as it gets faster and faster that doesn't mean we're prepared as a species or uh or as a biological entity that we're prepared for it to come at us that fast. You know what I mean? So I feel like it's a little dangerous. Am I making any sense here?

SPEAKER_01 1:03:50

No you're just smiling all the way to the mouth you know no it's just you've got your perspective I've got mine everyone has their own perspectives and and somehow we all muddle through um but I'm I'm uh I I have to be optimistic I can see dark sides don't get me wrong I can see dark sides but I I think that um you know we go into those dark periods and then we pop out of them faster than ever before um and and uh I again I just see so much potential for good the the if you want optimism I had a conversation with a colleague yesterday I pointed them uh in biology I said I said if you really want to see optimism go to the iGem program the International Genetically engineered machines program it spun out of MIT in the early days over over 23 years ago um but now they operate they run a big jamboree out of Paris and it pulls together thousands of kids working in digital biology and and that's where you get the optimism that's where you see the next generation coming in you know unjaded and wanting to build a better future you see it in the biopunk communities like people that are using these technologies in really creative exploratory ways they're not the big pharma companies they're literally the up and coming generations that's fun and if you really just need a better perspective on humanity and how it how amazing and artistic and creative it can be I tell people go to Burning Man honestly it's just uh it's an 80,000 person city that exists for a week and and the entire culture is gifting and art and community and fun. And and if you can't walk away from burning man with a big smile on your face and feeling you know we're crazy we're crazy collect we're people are individually nuts and collectively amazing that um you know it recharges your batteries and and there's probably a lot of other examples but um don't uh I I never slip into the depression side because uh you know there's ups and downs in every day and in life but but man there's just so much potential uh ahead of steam building up to make things so much better and it's coming bottom up it's available to almost everyone that's interested well god dang it I'm gonna lean into your optimism as long as I can today at least 10 minutes it's it's infectious so I'm gonna lean into it see if I can get through the day with that kind of optimism um I appreciate you letting me push back on you.

SPEAKER_00 1:06:25

I like your style he is Andrew Hessel he's got more jobs than me uh but he is on the cutting edge of what are we calling it now data biology? What did you think No no digital biology it's following in the footsteps of digital computing yeah uh so uh thank you Andrew for playing today again thanks for letting me push back and uh thanks for being our Fresh Face in hell keep that smile on your face buddy thank you man a Fresh Face in Hell with Jonathan Evison is brought to you by Fresh Face Pods and produced by Jason Botkin and yours truly. Check us out on Instagram YouTube or at our website at FreshfacePods.tv don't forget to subscribe to our newsletter for updates and special content. And if you love the podcast by all means run it and buy all of Jonathan Evison's award winning novels wherever books are sold