Amy Webb and Andrew Hessel: the genesis of The Genesis Machine

Andrew Hessel and Amy Webb, image courtesy of Fortier PR

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Since the earliest days of genetic engineering in the mid-20th century, scientists have been pushing the boundaries of what it’s possible to do with the underlying code of life, DNA. With the advent of high-speed DNA sequencing technology, genome engineering tools like CRISPR, rapidly improving methods for synthesizing DNA in the lab and an explosion of software and AI, we’re entering a whole new world of biology.

Not only do these genetic engineering tools bring potentially huge advantages for society in terms of health, wealth and wellbeing, they also bring risks and dangers. So what’s actually possible, versus scaremongering science fiction? What’s coming fast down the pipeline that we need to know and think about? And how - and who - decides how this stuff should be regulated?

All of these questions -  as well as the scenarios I outlined - are explored in a new book called The Genesis Machine: Our quest to rewrite life in the age of synthetic biology. It’s authors are Amy Webb, founder of the Future Today Institute, who spends her time digging into the technologies that are changing the world, and Andrew Hessel, a geneticist who comes from the frontiers of genomic science and is the co-founder of Humane Genomics, a company creating novel gene therapies, and Genome Project-write - an international collaboration accelerating the development of DNA synthesis technologies.

It’s a genuinely fascinating book that certainly made me think in a new way about ideas and technologies for engineering life. I had to start our conversation by asking where it started - what was the genesis of The Genesis Machine?

Amy: I research emerging technologies for a living. And while I was working on my last book about AI, I kept coming across the same few companies that are building the futures of AI ... also seemed to have some role in what at the time was a new field to me, this synthetic biology. And I was very curious to know why, like, why does Microsoft care about biology? Why does Google care? Right?

Amy: So that started me down the second rabbit hole and fascinating area, but I'm not a scientist! And so, I had a pretty clear idea of the sort of non-science related themes, but Andrew, who is the scientist, is the scientist side of the project. So maybe I'll hand it over to him.

Andrew: Thanks Amy. And it was really, synthetic biology is just my life. I'm not a bench scientist anymore, I have been in love with the technology of synthetic biology for over almost 25 years now, as the genome project started to wind down and I realised that writing genomes and writing genetic programs was going to be the future.

Andrew: And so I've been privileged to watch this industry grow and be a part of it. And I have not written a book before, and when Amy called and said "would you like to write with me?" it was a dream come true.

Kat: So you've used the term, the "Genesis Machine" to kind of refer to this idea of - it's biology, but it's applying the principles of engineering and software to it. So how did you decide, okay, this is the sort of stuff we're interested in and interested in covering.

Amy: So it's kind of a multi-layered title. So there is a section of the book that talks about where do we think life comes from, from a biological perspective, right? There's also a section of the book about the sort of religious perspective, the connection between what we believe and how we approach science and have always done that. And then there's yet another layer of the book that has to do with the economic and academic and like the actual machine that's responsible for bringing this incredible technology into the world. So the idea of "Genesis Machine" was really a play on those different areas. Now, what do we include and what do we not include?

Amy: That's interesting. Cause that was one of the first very, very, very, very long conversations we had was me saying I've got like an entire room full of stuff that I've read now. What is the way to, like, there are so many facets to this?! [laughter]

Andrew: Synthetic biology touches so many different things. So we cover the core of it, which is getting the technology to design and engineer genetic programs, using digital tools. Which is making it a lot more like programming a computer, except instead of programming a digital machine, we're programming a biological machine to do hopefully useful things. So we cover that core technology, which is the software tools, the DNA printers that now allow us to compile that genetic code into something the cells can run, and some of the cellular machinery.

Andrew: And then we start looking at all the various things you can do with this technology. And there's nothing that it can't touch because biology, we live in a living world we're made of this stuff. Everything around us is made of this stuff. So it has the potential to touch even more than computing touches.

Kat: So when I was doing my PhD, I think probably the best part of 20 years ago, so much of this molecular biology technology, you know, now I look back and it feels like it was just in its infancy. You know, you could order a little short length of DNA to do some PCRs with. You could do a bit of cutting and pasting and sticking bits together. And we were all terribly excited because, you know, we had PCR machines to do this for us, not the water baths like the guys in the seventies!

Kat: Did it surprise you that even what we can now when you kind of came to it and, we're looking at this, it's like, "we can do this already?!"

Amy: I guess, no - only because, I think if you talk to people in the field, synthetic biology, very similarly to artificial intelligence where I do have some deep technical knowledge, these are terms that kind of mean everything and nothing. Right? They're they're weird. They're like strange terms. So, um, you know, within this umbrella, I would say is CRISPR. You know, there are many other technologies. And so, I guess I would say I'm not surprised at what can be done now.

Amy: I do worry a little bit that this is complicated stuff, and I do worry a little bit that when the entire world gets wind of what we can do now, you know, there may be some unscrupulous investors that decide to throw a bunch of money at something and then expect the next big product in the market, you know, like right away. We saw the same thing with AI and it's like, this is basic research! Like give everybody a little breathing room, let 'em have some time! Um, which is not to say that there's not plenty of things to invest in, but I think we need to have some expectations set in a way that's meaningful.

Kat: Yeah. It's fascinating. I'm seeing, you know, working in the life sciences industry, you see every drug design company now is like "we're an AI drug design company!". Everything's AI and I'm starting to see ...

Amy: Well, but everything literally is AI, including this conversation that we're having right now!

Amy: So, I mean, like everybody's been using, you know, bits and pieces of AI in various degrees of sophistication for a very long time so...

Kat: So maybe Andrew, you could actually talk us a bit through then, where are we at with these kinds of technologies? I mean, what then is actually possible to do with these kinds of synthetic biology approaches?

Andrew: Well, we're about 20 years into the field, which means we're still in its infancy, given how powerful it is. And I live in a constant state of frustration because as good as the tools are today and as transformative as they are over the old generation of very hands on manual techniques, they're still just scratching the surface of where they're going over the next decade or two.

Andrew: I really am forward looking in this and realise, wow, we have so much to learn and people will probably be shocked at what we can do today if they're coming into it cold, but they're going to be even more surprised going forward.

Kat: So let's turn then to the futuristic scenarios. I really enjoyed reading the book and I now chatting to you on this call, I can imagine you guys just sitting there and going, like "what about this? What about that?" What was the kind of the creative process between trying to look at the science now, the science that might come at and creatively paint these scenarios, and then maybe we can talk through a few of them as well.

Amy: Yeah, so there is an art and science to scenario writing and to forecasting. So for them to be effective tools, to help glimpse plausible futures, you really have to start with data and methodically sort of think through, you know, "if this, then that". But you have to keep coming back to plausibility. And when I do this, I actually use models and there's, there's a whole process.

Amy: Now there's scenarios thinking. And actually this book is kind of designed to help people do that. Our goal here is to get everybody thinking constructively about the future. And you don't have to have be a scientist or a social scientist to be able to that. Now I'm remembering a spreadsheet with our initial brainstorming that had, I don't remember how many scenario ideas that were in various stages of development.

Amy: There was three of them that I spent a lot of time with because they were very personal. One had to do with that fertility center from the future, which, having spent many, many, many, many, many hours in fertility centers over about a decade, attempting to stay pregnant - get pregnant and stay pregnant - you know, at some point I think I read every brochure in that place and I found it to be so frustrating. I actually have a stack of those brochures in my office. And as I was thinking through, I mean, a lot of this, a lot of my initial desire to even work on this was like: there's gotta be a way to make babies easier, better, more efficiently. Anyways, so I was going through all my stuff and I saw these brochures for the fertility centre, which at some point I hated having and looking at, and I saw them in a new light. So that's where that came from.

Amy: The other one, there's a scenario about this thing that happens in a lab and the FBI gets involved. That one came because I was curious to know if something were to happen, like a hack, like an unattended consequence, who's in charge in the United States? I talked a bunch of friends in government, at State Department, DOD - all over the place. And Andrew and I talked about it, we all talked about it! And the consensus was: nobody knows! We do not have a plan for a cyber biosecurity incident. So basically what you read in that short scenario was really me going through methodically, asking every one of these different groups and departments, trying to figure it out.

Kat: Can you just talk a little bit into that scenario? Because this really fascinated me because on the surface it's like cyber bio hacking, this seems nonsense! But like you say, when you go through the steps, you like - crumbs like, what are the checks and balances here? Can you just talk through what you imagined there?

Amy: Yeah. So one of the papers that I read had to do with some pretty sophisticated advanced researchers in Israel who kind of do all kinds of crazy weird fringy hacking for real, like as part of their academic research. In fact, that exact same team just cracked another kind of crazy thing outside of the biospace.

Amy: But anyways, long story short. They showed that there was a vulnerability in the genetic code that get sent away and the stuff that gets sent back.

Kat: So this is like scientists saying, okay, I wanna order up this piece of DNA for my research, tap, tap, tap, tap, tap... You send it to a company like me ordering my little bits for PCR years ago, on a much grander scale.

Amy: I think that's right, Andrew. Right?

Andrew: There are so many vulnerabilities here. You can, you can hack the synthesis side of DNA. You can hack the sequencing side of DNA and actually do code injections in the actual DNA that's being read. There's so many cyber bio vulnerabilities at this point.

Amy: This particular one was functioning more like what's called a MOM or a man in the middle attack, which if you have like an outdated browser... You should update your browser! Update your stuff! Now is a PSA, update your priors and update your passwords.

Amy: Anyways, it was more creative than it was highly technical, but what it proved was that, you know, you can have the safest lab on the planet. And I do believe that most of our labs are just very, very, very safe and secure when it comes to the handling of materials. But when it comes to IT, and firmware, and all the stupid, boring stuff that most people don't update anyways, you know, and most companies kinda "eh" until there's a problem - that's the issue. And so, you know, one of the things that we've uncovered is that it's actually not that challenging to really muck with very benign code and on the other side of it gets something potentially pathogenic.

Amy: So the scenario is about that and the basis of it is the data and the paper. But then after reading the paper, you know, I do a lot of work in DC and just, I was calling friends and saying like, "Hey, I just read this paper, what if this actually happened? Like what, who's in charge?"

Amy: And I talk to folks in DoD, I talk to folks at... Anyhow, various layers and levels of the government. And the answer is maybe a four star would take over if it was truly catastrophic and like, you know, they have processes, but there's nothing specifically designed for this. And that really does represent a true threat because there is no such thing... I mean, I don't think most people are working in situations anywhere anymore where it's just you, some liquids and a pipette, everybody's using computers. And that means that you have to really consider your security protocols from a cyber point of view, because we do have cyber biosecurity vulnerabilities now that need to be dealt with.

Andrew: I have been concerned about many different layers of the bio and cyber architecture for a while, because this is really powerful stuff.

Andrew: And as we learned with COVID, as we've all learned over the last couple of years, something like a virus may be relatively within our reach of engineering today - it is. But the defense of a virus can be global and cost trillions of dollars and throw our lives into all sorts of problems! So I've been very interested in the biological vulnerabilities and the fact that most people don't pay any attention to things like viruses and the fact that we can engineer them. And just the cyber layer and the hacking on top of that biological insecurity is gigantic.

Andrew: So this is something we really have to start addressing now and being aware of and looking forward, particularly as the CDC says, it's already having to reorganise just for the next, you know, for the next outbreak.

Amy: And I would just add, what you're witnessing right now, the three of us are talking, is what we would like for everybody to be doing. So you've gotta buy out. You've got, you know, two scientists and a lady who knows a bunch about AI and cyber, on top of the future stuff. But get, you know, us talking about is a great way to start spinning up what might happen.

Amy: We've really become less multidisciplinary. We've become so highly specialised that's hard to get people to overlap and have these types of conversations, which are really, really important. And probably you couldn't get to the same level of insight if you didn't have a multidisciplinary group.

Kat: I think it's really important to come at it from the area of like, what is true, like what is actually plausible? What is feasible and not just what's panicking. Cause I remember, you know, when we had the era of nanotechnology, there was the fear of the grey go. And that the people working on nanotech were gonna make this grey goo that was somehow gonna get out and dissolve the world and you're like "Really? Really?"

Kat: And I think with the genetic engineering, it's like: oh, you know, people, it's gonna be someone in their garage making a superbug or, you know, we're gonna be genetically engineering designer babies, and it's all terrible! And you don't think it's like, well, some guy in the basement is actually just hacking into a labs, computer and ruining someone's experiment by putting a pathogenic virus into it.

Andrew: I generally think mother nature is the biggest hacker. You know, it's not like there's a master design. And so we've, you know, everything natural has kind of found a way to navigate that ecosystem. And even bacteria, CRISPR is a bacterial defense system. So what I think is really the new layer added on top of it is, as we start to intentionally engineer biology, now we get these human intentions going in. And we understand, and can draw examples from anywhere in nature, you know, so now we can take hacking to a new level.

Andrew: So we also have to take our immunity to a new level. And that's kind of the challenge for our species at this point probably .

Kat: And that does lead me onto the question about, well, how do we figure out; what should we do? What can we do? How do we protect ourselves? Who decides what is allowed? And what's not allowed?

Kat: You know, cast your mind back. There was the Asilomar Conference back in the early days of genetic engineering, where all the scientists and some other people got together and were like: "Yes, we can do this. No, we can't do that. That's good. That's bad." This feels like a huge genie that's already very much outta the bottle! So what sort of framework can we start thinking about for how to decide as countries and as a global society, like what, where are the limits here?

Amy: So I'm happy you brought up Asilomar because that conference was actually covered by Rolling Stone. So I know Rolling Stone is - and forgive me, the company that publishes Rolling Stone - now I know it's like, not as cool as it probably was, you know, 20, 30, 50 years ago. However, in its heyday, when that conference was planned, the folks who planned it were brilliant. They invited outside media, but a whole variety of people. It wasn't just science journalists. And Rolling Stone ran a cover story! So on the inside is multiple pages of this conference, black and white photos. In the midst of all these super cool rock stars are a bunch of schlubby looking scientists. But they are covered as though they're rock stars. And this was not particularly glowing because there were arguments that were had. But again, what was the point of all this? It was to bring that dialogue into the open.

Amy: And this is becoming, I think even more challenging as the nature of intellectual property becomes more of a issue all over the world. People are just not willing to talk about what work they're doing. If you look at research papers, there are fewer and fewer, like "here's how we did it". And so that's a bit of a problem: we don't want all this stuff shrouded in secrecy and everybody can still make plenty of money.

Amy: So we actually in the book propose nine specific risks and there is an entire whole section of the book that has to do with what we think ought to happen to help ensure that this work, that synthetic biology is developed, you know, in the best interests of everybody in a way that's sustainable.

Andrew: The short version for me is I just think that sunlight is the best disinfectant. Transparency is absolutely important with this. And we can't have filters on the information as much as possible if we're going to, if we're going to be able to collaborate.

Andrew: So, I'm thrilled that synthetic biology has come along, digital genetic engineering or genetic engineering supported by digital tools, in a time where we've also learned how to create distributed immutable databases and ways that information can be free. I think that's a really good convergence for the future and it gives me hope.

Amy: And for those of you who aren't, who are in the cheap seats and, and don't know what "distributed", " immutable", all those little buzzy words mean - Andrew's code for blockchain. Which I know, I know...

Kat: Blockchain klaxon! [laughter]

Amy: We don't mean like Blockchain, capital B. It's more like blockchains is in, like, this is a really smart way to help safeguard this very important information and but like, keep it out in the public.

Kat: So I wanted to kind of circle back to where we started right at the beginning, Amy, where you said you'd got interested in this because companies like Google and Microsoft are getting interested in this, and clearly there's gotta be money to be made if big corporations are involved. And you mentioned the issue around intellectual property.

Kat: So, who owns the products of this? Who owns the tools and technologies? Like, is this just stuff for the rich, stuff for corporations? How do we do this? How do we make the economics fair?

Amy: Well, let's start with one question that you asked us in that blob of questions...

Kat: That was a very big question, I apologise!

Amy: And that had to do with ownership - who owns it. And that's a difficult question to answer. The answer to that question is: it depends. On where in the world you are, who got their paperwork filed using expedited shipping... I mean, there's a lot that's packed into it.

Amy: So who owns it is a very challenging question to answer. Who should own it is the discussion we ought to be having. And should anybody own, or should it be more about processes than the code itself? And this has been part and parcel of this entire field of biotech since its founding. You know, when they figured out insulin, synthetic insulin, they like gave away the patent because they wanted to make it free. But then, there were immediately arguments afterwards about that. So this question has been around since the beginning.

Kat: And I guess Andrew, from your perspective, you work for a company and organisations that are trying to create DNA, this "DNA, right" idea of things. And I guess in the world of IT, people have their code and that code is copyrighted to them. So like, does that sort of work the same in the world of DNA?

Andrew: Well, you know, we're figuring it out. So I came from... my first position out of school was with the pharma company. So I saw the IP side and how much money could be made with a little bit of biological IP in the pharma space. So there's money to be made in lots of different layers, but on pharma, it was just amazing. 'Cus biology essentially prints your medicine and manufactures your medicine and it can worth billions of dollars.

Andrew: But I walked away from that realising I wasn't seeing the dynamics in pharma that I saw in cell phones. Which are also incredibly advanced technology and take many, many, you know, experts to build - but they got cheaper over time and more powerful over time. I wasn't seeing that in pharma and I realised something has to change. And synthetic biology I believe is actually going to be the technology that drives that change. But we haven't seen that economic shift.

Andrew: You asked if this is only for the rich? No, no, absolutely. At the beginning it might certainly be restricted to elite groups and the rich and the people that are kind of building the infrastructure. But I think the open source side of this is just going to explode because the technology that makes a vaccine or makes a cancer drug or an antibiotic today is really available to just about anyone. And even small individuals or small groups can replicate a lot of that work. So we're gonna see some really profound economic shifts happen in biotech over the next one.

Amy: Right, and I actually think that the place where we'll see it earlier, is biotech applied to agriculture, which we don't normally think of as together. But again, there's long history of, you know, editing and tinkering with seeds and things like that. But the reason for this is, we have an existential threat in our current climate crisis. It's abundantly clear that the various nations of the world are not gonna get together and everybody's gonna give up some stuff and agree, and - like it's not happening! Synthetic biology fills that void. So there are solutions, there are many different ways to use this very technology to do things like bring sugar cane production inside of Brazil, abandoned Brazilian mines. It can totally be done. It just hasn't been done yet.

Amy: So, so there are lots of creative applications of this. And I don't think that this is a "nice to have alternative" as much as it is "we're gonna need this stuff if we want to survive". I believe that, the data proves that out.

Kat: What about the geographical element here? You know, we like to think we're all a globalised world and everyone, you know, the world global scientific community is all in this togethe. But there are countries and powers and axes. Which countries are really investing in this direction. And you know, if there are huge gains to be made from solving things like the climate crisis, through this kind of egineering, you know, where should we be looking, for where these technologies are really gonna start blooming?

Amy: It's the usual suspects, right? So China and the United States are the fore-runners. Now it doesn't mean there's not plenty of activity happening elsewhere, but those are the fore-runners.

Amy: We have in the United States, we have not had a lot of true long-term leadership at the government level on what is our long-term strategic plan when it comes to biology. We don't have one. And I'm not saying that the government should determine that and tell business what to do. That's not it. But it's like, who's got the vision? The vision is, you know, everybody do your thing and we'll deal with it.

Amy: China is not in that situation. That is an authoritarian regime that sees synthetic biology among other things like AI, as part of its long-term growth plan. It is investing heavily, heavily in these areas. And again, I think we ought to ask ourselves is that, you know, is that what we want? The United States pushing sort of a more capitalistic view, China pushing a more authoritarian view. And the role, I guess, for Europe has to do with regulation as it often does, innovating in the regulatory space.

Kat: Andrew speaking about regulation, is there anything in the technologies that you've seen and think are coming that you think should be outright banned globally or like really heavily controlled? Is there anything that you'd be like, yeah, that probably shouldn't be allowed to happen.

Andrew: We mention this in the book. We believe that virus engineering really needs a lot of oversight and that's viral "gain-of-function" engineering, making them more pathogenic, making them more deadly, making them spread easier. This research should essentially be banned. There's really no reason for it today. But it's not just viruses. It could be fungal species that can produce humongous numbers of spores and are almost impossible to eradicate once they're in the world. So we really have to look at epidemic disease and organisms that can cause this type of disease and the engineering of these very carefully and, and watch them very carefully.

Andrew: Because one thing about these tools is they're making incredibly powerful tools available to smaller and smaller groups of people for less and less money. And we have not yet built any type of architecture for keeping global watch on how those tools are used and by whom, in a way that's similar to cyber security - which of course has its weak points, but is working well enough to keep our digital world up and running.

Kat: So that's the kind of, that's almost like the end of the scary section. I did want to come back to talk through some of the scenarios in the book that I just thought were a lot more fun and fascinating. And I don't know which one of you wants to put their hand up and be responsible for the food critic of 2037 scenario? Because I absolutely loved that. The idea that you could go into a restaurant and you could eat like a cultured meat from any imaginable species or extinct species. Who's is that.?

Amy: So that one, I had a little bit more of a hand in only because I don't eat meat. And when we started talking about cultured meat, I was like, well, I would eat that meat, right? That meat is healthier. It's gonna be healthier for me. It's healthier for the animals, you know, it solves a bunch of things. And then I was like, well, if we're gonna culture chicken, like what wouldn't I eat at that point? Right? I would literally eat anything. Like Cocker spaniel kebabs? I would eat that. Panda bear steaks. I would eat Panda bear. Like the cutest Panda bear you've ever seen in your life, if it was cultured, I would totally eat that.

Amy: And that actually sparked a debate at our dinner table. So we're talking about this, like what, what wouldn't people eat? And then my daughter was like, people, could you culture and need a human meat? And then it was really hard. And then we had like a long debate about - she's 12, so I, I take this as a good sign that she's thinking like in a very expansive way, not that she's a future cannibal or something. But it did, we did say like, what constitutes cannibalism at that point. Right? So it was just spinning, spinning these things out over and over again.

Kat: So to wrap up, I want to ask each of you in all the data and all the stories and all the papers, the people that you've spoken to, what is something that you've come across that sounds like it should be sci-fi at this point, but is actually real that blew your minds a bit.

Andrew: I just wanna say, like what doesn't sound like science fiction that's real here! We are not looking, you know, a hundred years into the future in this book. This is stuff that's happening now. Just the fact that we are learning how the levers of biological ageing works sounds like science fiction, but it's happening now. And if you're a mouse, you're gonna live cancer free and a lot longer, you know, and eventually we'll get up to us.

Andrew: The other one that I think is incredible is that we can actually teleport organisms now from one place to another. And that's... that's right out of Star Trek!

Kat: Okay. Hang on. You've gotta unpack that. You've gotta unpack this a little bit. So how, how, how does this work?

Andrew: It works by taking an organism and let's keep it simple, we're not doing this with mice or people. This is working with bacteria and viruses and single celled organisms right now where we can take that organism, take its entire genome out and read it, digitise it. So now it's a file on a computer. We can send that file electronically over any of, in all these different ways. And on the other side, print that genome and boot up that organism a whole new instance of it in another place. And this is not, it sounds like science fiction, but it's happening now. And that's how we're actually sending samples of a new outbreak of an engineered bacterium or virus around the world now.

Andrew: So we're starting to actually get digital libraries of organisms that can be printed on demand or teleported anywhere we need them. And eventually, it will start moving up the tree of life into more complex organisms.

Amy: So I'll leave you with one crazy thing that sounds like science fiction to me, that I'm actually still having a hard time wrapping my head around. And that is a computer called dish brain. So dish brain is a computer system, made of about a million brain cells attached to, let's call them some plates. Okay. So in a similar way that electricity moves around traditional compute architecture. This is kind of modeled using that. So it's kind of a Petri dish full of cells, wired to a what looks like a chip.

Amy: Okay. So this system, like many other AI systems was asked to play a game. Early AI systems had to learn how to play Pong and it took them a while to figure that out. And then over time, without humans in the loop, the systems were able to figure out how to play Pong -that game from, you know, a forever ago. Dish brain learned how to do that orders of magnitude faster than any AI that has ever existed.

Amy: And the researchers that were working on this project. We're trying to figure out how that happened. And what they think happened is that this system sort of "believed" and I'm using believe in air quotes, but the system "believed" air quotes itself to be the paddles. That it was actually the game moving around.

Amy: That is not science fiction. That is, that is science fact. That is the year 2022. Now what does that imply? Lots of things. Right? Where do we go from here? What does the next 50 years look like? I don't know, could look like a lot of different things.

Amy: But better to be open to signals of change now so that we don't have this collective sense of whiplash. And then way after the fact attempt to regulate or attempt to tamp down, or God forbid, we find ourselves in a serious geopolitical conflict because of biology and technology merging in ways that people didn't expect or anticipate.