Synthetic Biology with Adrian Woolfson

[00:00:00]A chap called Brian He who is at the Ark Institute in Stanford did actually make the first ever totally synthetic species. It was a virus, a good virus cuz it's a virus that can kill antibioticresistant bacteria that can kill us, right? and he actually used um AI on a computer to design a completely new viral genome which technically met the criteria for a new species. So we have created new life.

[00:00:32]The only proviso of that is that technically a virus isn't alive because it has to infect a bacterium to reproduce. Keep watching to learn more.

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[00:01:43]Thinking Aloud.

[00:01:46]Conversations on the leading edge of knowledge and discovery with psychologist Jeffrey Michionlo.

[00:01:59]Hello and welcome. I'm Jeffrey Michionlo. Our topic today is synthetic biology. My guest Dr. Adrienne Wolson is the co-founder, president, and CEO of Janeiro, a synthetic genome design and construction company based in San Diego, California. He is author of Life Without Genes, the history and future of genomes.

[00:02:30]Also, an intelligent person's guide to genetics. Additionally, he's authored over 160 scientific papers, book chapters, reviews, and patents.

[00:02:44]His newest book, about which we will be discussing today, is on the future of species: Authoring Life by means of artificial intelligence.

[00:02:57]Adrien is based in San Francisco. And now I'll switch over to the internet video interview.

[00:03:06]Welcome Adrian. It is a pleasure to be with you today and likewise. Thanks so much for inviting me on the show Jeffrey. Really appreciate it.

[00:03:16]>> You have a fascinating background uh in genetics and in particular the idea of synthetic life. People, I think, are familiar with genetic engineering and gene splicing and the possibility of modifying, consciously and deliberately modifying various organisms, even such things as viruses, for the purpose of medicine for for one thing. But the idea of actually creating new life forms is is something that's almost never discussed in public. And I gather that is one of your primary focuses right now.

[00:03:59]>> Ever since the beginning of human history, humans have dreamt about being able to create life, you know, and and modern fiction uh kind of recapitulates some of those themes. Um and then the question really becomes, is life something that you can create denovo, you know, and if so, how would you do that? and and it turns out really that all living things are based on systems of heredity and and the physical basis of that is the genome right genomes contain the not all the information to build us but the core information you know the essential you know uh non-negotiables if you like to build an organism right so if we uh learn how those rules operate you know the kind of our genetic instruction manuals which are our genomes. If we can unpick the grammatical rules that determine how genomes speak to us, in other words, build us, right? Then yeah, you know, we we could entertain the possibility of building new organisms. And in fact, um, the co-founder of my company, Janiro, a chap called Brian He, who is at the Ark Institute in Stanford, did actually make the first ever totally synthetic species. It was a virus, a good virus, cuz it's a virus that can kill antibioticresistant bacteria that can kill us, right? and he actually used um AI on a computer to design a completely new viral genome which technically met the criteria for a new species. So we have created new life.

[00:05:41]The only proviso of that is that technically a virus isn't alive because it has to infect a bacterium to reproduce. I can tell you Jeffrey that it will be a matter of, you know, 12 months or less before we've actually built the first synthetic bacterial species. And bacteria are living things, right? So, we're on the road to building life. That's just a simple fact. No, a bacteria would be a a single-sellled organism with many different components, a nucleus, and all sorts of interactions among the components.

[00:06:20]>> You're right. Except um bacteria don't they're they're what are called procariots. You know, the kingdom of life, there are actually three kingdoms of life, but the two main ones are ukariots, which are cells with nuclei like us, right? and and all animals and then proariots which is a much simpler type of design of the cell which is what bacteria are actually. So they don't have a nucleus but they are living things and they're complex and they have lots of components and I would say that even today you know they're pretty computable meaning that you know we we we can design design them on computers. uh to date we haven't made an entirely new species of bacteria right but we can definitely extensively redesign existing ones using AI and it's just a matter of time before we we are able to literally totally redesign a bacterial genome having said that you know we that we have already made synthetic in fact one of my other co-founders Kaihang Wang at Caltech did actually uh with a colleague of his in Cambridge Jason Chin build an entirely synthetic bacterial genome and then they recoded it. They changed the kind of logical rules which map DNA sequences onto amino acids. So they didn't just copy nature, they kind of radically reimagined it, but it was still the same species of bacterium that they ended up with. So they didn't make a new species.

[00:07:58]They did make a new technically make a new form of life because this was a totally you know re-imagined genome but it it was of the same species right but in the future uh I believe we'll be able to to design entirely new species using AI to guide us to be clear for our viewers who don't have a background in biology a a genome I understand is a collection of all the genes of of a particular organism. But I would imagine that a genome must be much more sophisticated than just that because there's a question of how these different genes interact with each other.

[00:08:40]>> Yeah. The way the way I think about it is, you know, some of us as kids used to build these model airplanes, right? You know, the ones which are made of plastic and they came in a little packet and you'd glue the parts together, right? So I think about a genome in two ways, right? You've got the components which are all the little parts that come in the packet and you you join them all together and you make the airplane, right? And that's fine, but but you can't do that unless you have the instruction manual as well, right? And the instruction manual tells you physically how to connect those parts together, right? So, you need the parts and you need the instruction manual, right? And actually in the in in the case of genomes, you kind of have both kind of woven together, right? You have the components which are the genes and then in between the genes and sometimes incorporated into the genes, you have the uh the kind of instruction manual, right? So the genome contains everything you need to build the model airplane kit or in this case the organism, right? The instruction manual and and the components. That's how I think of a genome. If you take the book analogy, you know, where you're writing down letters because DNA is made of four chemical letters, you could think of it uh each chromosome as being like a volume of a book and you have multiple volumes in a library. And all of that information is what you need to make an organism, right? That's the genome. It's like the repository of all the information to build the components and and the instructions of how to put them together. I gather that Francis Crick worked out a lot of the genetic code back 50 years ago, but that there's still many aspects of the coding that goes inside of a genome which is still eluding us. and and that your expectation is that eventually using artificial intelligence we'll be able to read the entire code. Yeah. So Watson and Crick um basically established through modeling that DNA has is you know forms a double helix and that one strand acts as a template to synthesize the second strand and that the information in DNA is encoded in combinations of the four chemicals that DNA is made of. So whereas English the English language comprises an alphabet of 26 letters, DNA has an alphabet of just four letters. Right? In the same way that the English creates words by combining those 26 letters, DNA encodes information by combining these four letters into different sequences. Right?

[00:11:28]And so the question is it's almost like you know going to ancient Egypt and looking at hieroglyphics and saying what do they mean? How do we how do we interpret them? Right? And the genome contains many layers of meaning. The simplest layer and you can read a genome by what's called sequencing it. Right?

[00:11:47]And sequencing a genome means literally just reading the order of those four letters. It's like reading a book and saying this is the sequence of letters.

[00:11:56]Right? And that's how we get the meaning, right? And in genomes, um it's the sequence of those four chemical letters that encodes information. Now, up until now, we've been able to uh quite easily work out the the sequences of genes and then work out what the genes do because genes, classical genes, so to speak, encode proteins and those proteins have functions, right? It turns out though actually that the genes that code for proteins, those actual components make up just a tiny portion of the genome, maybe less than 1%, right? The other 99% of the genome uh is involved in regulating those genes, right? Switching them on and off in a particular pattern.

[00:12:46]It's like the lights on a Christmas tree, you know. They can either just go bling bling bling bling, you know, on and off, or they can have a pattern that goes, you know, and and and you can think of the regulatory region of the genomes as controlling that the pattern in which the lights on the Christmas tree go on and off. And you can regulate that pattern, right? And if you regulate it in one way, you can make a cell in the brain. And the cell in the brain might go, you know, and if you regulate it another way, you get a cell in the liver, you get another pattern, a different pattern in the kidney, right?

[00:13:20]And then at a higher level, the the kind of aggregate of all those different patterns create a certain species. You know, the reason that you're a human and not an octopus is both due to the fact that you have some different genes and some shared genes, but also you regulate the genes that are the same as an octopus in an entirely different way.

[00:13:43]Right? And when I say the same, they're not identical, but they they could be very some of them are very similar, right? So basically nature takes a kind of basic set of genes a kind of minimal gene kit and then slowly builds on it like a Lego set right and and in creates new bricks and new ways of regulating them and that's how you get one species rather than another. So the way I've described it to you should I hope to your listeners indicate this this process is kind of programmatic right in a sense that one can see that if you switch things on and off in a certain way or you put in more or less components or different components then eventually you should be able to create a kind of general law or a kind of grammar if you like which describes how doing one thing or another gives you a different outcome. Right? So how is it that this set of genes switched on and off in this way build a giraffe whereas this set of genes switched on and off in a different way give you an ant or a kangaroo or a virus you know and that secret if you like is like the secret of hieroglyphics. It's the secret of life, right? And in my book, The Future of Species, on the future of species, I kind of argue that that logic, that grammar underlying the expressions in the language of DNA, just like the expressions of English in a book, a narrative structure or novel should be decipherable, right? Eventually. And once we produce the grammar book of life, which could be universal for all species, then basically we control biology at that point, right? And at that point we could say, look, we want to build this organism or that organism.

[00:15:37]And our computer tells us it will look like this or behave like this or hey, we want to understand human health. We want to get rid of this disease or that disease. We want to live a bit longer or more healthily, you know, and and this is the kind of reverse engineered knowledge of ourselves that will be a direct product of understanding these grammatical rules of biology. So the answer to your question, that was a long answer. The short answer is we know very little about how genomes are regulated, right? But that understanding is increasing on a daily basis. And it turns out that a lot of that information isn't only in the sequence of DNA. It's in how the DNA organizes itself in three-dimensional space. It kind of twists and turns and folds open and unfolds. It's like a machine and and and those movements in space and condensations and expansions are a kind of code in itself. But in order to understand that code, we need to look at the genome in a in a different way by observing it in three dimensions. The onedimensional sequence, the chemical sequence is just the entry levelvel level of understanding if you like. I have done a few interviews on the topic of epigenetics and which seems to have to do with the regulation of genes and the suggestion has been made that it it invokes sort of the memory of Lamarian genetics. The idea that things that are learned by an organism can be passed on.

[00:17:18]>> Epigenetics is one of the many layers of information that's superimposed onto the genome. So I described the genome as the kind of foundational information to build an organism. Uh but but genes aren't everything. They the foundation but to get to the final organism there are additional layers of information required. Epigenetics is one of them. And epigenetics involves as you correctly say sort of a chemical modification of DNA which can activate or inactivate uh a gene right uh or or you know or a regulatory region and um although epigenetic patterns uh are generally uh self assemble or inherited there is evidence you're absolutely right that um there may be a Lamarian component to that meaning that an experience in your life could change the markings on your DNA permanently in a way that is then passed on that's inherited right and there is good evidence for this actually like uh tra you know of trauma for example in mice can apparently be passed on uh epigenetically rather than behaviorally right so that you know it's not an area that we understand terribly well But it seems like there is some truth in the Lamarian perspective at least at the level of epigenetics anyway. Not not in the sense of giraffes the one we learn at school but giraffes necks are long because they stretch them right but this is a more kind of subtle and sophisticated um rendition of the Lamarian theory.

[00:19:04]I'd like to go back to the statement you made earlier that you you think it's possible within the next 12 months that a a laboratory somewhere will create a synthetic bacteria.

[00:19:18]>> Yeah. You know I said 12 months you know it may be you know 12 24 you know 36 fully you know it's going to next couple of years right but the reality is in the history of you know life on earth or or even humankind it's just it's irrelevant you know even if it was 10 years right you know it's funny I often have this discuss kind of discussion with folks about timelines right and people now they they want everything to happen like yesterday right but you know think about it just think how far we've come in the last, you know, 100 years, right? You know, so in 1826, let's say, right? Like we didn't even know what a gene was. We didn't know what DNA was, right? The the idea that we could edit genomes or write I mean, you know, this 100 years in the history of life on Earth, which is 4 billion years old, is is, you know, it's just a a fraction of a hair breath, you know, of time, right? It's it's an irrelevant amount of time and and yet in that hundred years we've just skyrocketed on knowledge you know so just imagine if we were having this conversation in another hundred years where our knowledge is is expanding exponentially you know what what would our interview be like in a 100red years time I can only imagine we can't imagine right you know it's just going to be crazy where this is going to take us and one of the reasons I write wrote my book actually was just to say to folks, hey, you know, this is happening. You need to be aware of it.

[00:20:51]It's going to change everything that we know. You know, it's going to change the nature of life on Earth. It's probably going to change the nature of of humans, you know, potentially, right? And we need to make sure that we we we manage this in a in a really careful, sensible, safe, and responsible manner. and obviously in an ethical manner and in an equitable manner so that everybody benefits and in a manner that benefits the greater good of society right and that's why I wrote my book because whether it's today or in a year or in 5 years or 10 years you know it is going to happen you know biology is becoming an engineering material in the same way that steel became an engineering material and pretty soon you're going to start seeing things being built from biology which is a sustainable material, right? You know, you're going to be storing information in DNA. You're going to be eating food that, you know, made from crops who whose genomes have been rewritten to enable them to be heat and drought resistant and pest resistant and to have higher yields. You're going to be using bioeny. You're going to be using biioaterials.

[00:22:06]You know, it's a good thing, right?

[00:22:07]Because biology is sustainable. you can grow things but you know there are there are risks as well and we we can discuss those too right like any technology it's dual use and it's going to be up to us to ensure that it's used uh in a kind of safe and responsible manner and we're going to need governance and regulation to keep an eye on that too obviously one of the points you make in your book is that there needs to be a firewall between synthetic organisms and natural organis isms.

[00:22:40]I'm not even sure that the human being is a natural organism. It's possible that we were genetically engineered, but in any case, the firewall seems like an important idea in your book. And yet, I wonder, is it really possible? because we've seen examples of viruses for escaping from laboratories where presumably they had an adequate firewall.

[00:23:09]>> You know, the the old the old issue of whether whether COVID, you know, was created by humans and, you know, scape, we still don't honestly know the answer to that. But it's perfectly possible that that's true. You know, it wouldn't, you know, it wouldn't surprise me if that did turn out to be true. I don't know if it is true. It's just as probable that it came from bats, right?

[00:23:28]But we definitely have the technology to do that, right? So, it's it's totally plausible that it I it happened and you know, there've been there've been well doumented cases of of viruses escaping from labs. You know, that's happened several times around the world. So you're absolutely right that we we know from precedents right that it's very difficult to maintain 100% control over artificial organisms. Um but nevertheless um we you know we obviously need to do our best to ensure that we do things safely. Now um obviously you know there are bad actors who will always do what they they they're going to do and we need to do whatever we can do to keep an eye on those people and prevent them from doing things they shouldn't do. And then of course we may inadvertently do things and create you know havoc with natural environments by releasing organisms uh into complex ecosystems which at the moment are near impossible to predict and compute. And there have been really good examples where species have been even natural species have been introduced into new countries or you know ecosystems and they just cause havoc in ways that we would never have predicted. You know in communist China Mao you know started to turn against birds cuz he thought birds were eating all of the crops. So guess what happened? And the Chinese started killing all the birds and of course then all of the the the pests that the birds were eating just proliferated and they had a you know lost all of their crops you know it was they didn't think about that right and and and it's is sometimes difficult to think full circle and work out the consequences of interventions.

[00:25:19]You know, one of the key messages of my book actually is although I'm definitely an advocate of synthetic biology, I'm super cautious when it comes to releasing engineered organisms or synthetic organisms or new species into nature. And part of the key theme of my book is we have to really do everything we can to preserve nature, value nature, and make sure that we don't destroy Amazon rainforests and don't destroy the remaining wilderness and don't destroy the remaining species. We preserve and value them and and and see them as our precious heritage which we hand on to future generations. Right? We have a responsibility to do that. We're the custodians of nature's of nature but not the owners of nature. Right? So every time we lose a species like a so an apparently irrelevant species of beetle in the Amazon Amazonian rainforest, hey we don't know what value that that the genome of that organism might have. you know, uh, gene editing was was discovered in a in an obscure bacterium in a salt salt marsh in Alakan in southern Spain. Now, nobody could possibly have imagined that this uh, invisible, you know, microscopic organism could ever have any consequence for humans. But hey, it ended up in the invention of crisper. So what I'm saying is every species, however apparently irrelevant and inconsequential, may hold some secret that is going to be valuable to humanity. Actually, I don't think that's the main reason for preserving nature. We should just preserve nature because it's our heritage and you know, we've evolved with it and we have to value it. But if you needed a reason beyond that, then I'd just given you a good one, right? So, we're just going to have to be really, really careful about releasing organisms into the wild. We can create firewalls physically, but we can also create them genetically by changing the the genetic code of artificial organisms so they can't exchange genetic information with natural organisms. And we can also build in weaknesses into them so that we can get rid of them if we wish to. So, that that's the kind of thing I'm thinking of that. It's good to be thinking in advance of these things, but I imagine given human nature, there are going to be all sorts of groups of people all around the world, private companies, government companies with different ethical standards and and different different capacity to create the kind of sophisticated firewalls that you're talking about. So it'll probably there'll be laboratories ultimately in uh third world countries. I I think it's inevitable >> anywhere that could happen, right? I mean in America, you know, we're basically two nations trying to pretend we're one, right? But ideologically there are huge divisions even within the US, right? So how how if we can't even get alignment in the US on key issues, you know, how could we possibly hope to get global alignment on the governance and regulation of synthetic life? You know, it's almost impossible. And then there are kind of pariah states like North Korea and others where you know they're never going to listen to a global kind of alignment anyway, right? They're always going to do what they want to do.

[00:28:56]And you know, it's like game theory that you know, if you defect, you you you can actually get a tactical advantage, right? So, there's no doubt that um we're going to struggle to get agreement on how these technologies are used.

[00:29:11]They're going to be some there's going to be some significant diversification in perspectives on what we should and shouldn't do, right? But hey, that doesn't mean to say that we shouldn't try to define a kind of what we believe is an ethical and and sensible and responsible set of guidelines, right? So we have to aspire to that on a global basis and we have to try and enforce it as well. Right? And you know you you we we we can for example I mean I believe that we should for example never permanently engineer humans at the in you know in an inherit inheritable manner right that it should all be done so-called sematically which means that it's not inherited now I kind of assumed until recently that most reasonable scientists had that perspective right that that and that there was a global moratorum on on so-called germline gene editing. And then just the other day, I I I see a pitch from a company that's talking about responsible heritable gene editing, right? All of a sudden, out of nowhere, they're advocating this and it looks like they got funded as well, right? So, you know, it just shows you how within, you know, the turn of a on you can turn on a dime, you know, a kind of moral and ethical perspective on something which I think is still a step too far, right?

[00:30:40]But but people are now talking about it as if it's just inevitable, right? So we got to be really really cautious and careful and we must be strong enough to hold our ground and to have opinions and to ensure that our opinions uh form part of a debate. And that's a really key reason why I wrote my book because I wrote it for everybody not for specialists. You know there's a lot of history in there, philosophy, uh you know stuff about the arts, poetry, literature, AI, you know it's all there, right? Everyone can read it.

[00:31:14]Some bits are more difficult than others, but by the end of my book, and I hope you'll agree, Jeffrey, because I know you read it, right? It will change your perspective and you will understand this field and you will be able to participate in a debate and have a point of view, right? And that's so important because people are going to try and change human nature eventually. And that, you know, I I think that any any gene editing or rewriting should should only be used for medical purposes. But you know even the definition of a disease can be very idiosyncratic right.

[00:31:49]So it's not hard to imagine countries even today who would say that hey you know there's this terrible disease going around. It's called free will right? We better get rid of it. Right? Because we we don't want people having free will because then then we need things like elections cuz then they're going to have opinions, right? What we really want is everybody to agree with us and then we can do what we like, right? And and and there's, you know, and then free will becomes a disease, right? And, you know, we we know that there's a history of things being called diseases which today aren't called diseases. Hey, even loves sickness was once formally categorized as a disease, right? You know, you you know, so it's important. So if we if we if we argue that this should only be used for medical purposes, that's not enough, right? We then have to agree what a disease is, right? It's not simple is what I'm saying. No, I have in fact been in touch with a organization that's interested in developing genetic engineering for the purpose of engendering states of enlightenment.

[00:32:58]>> Right. Well, that's an interesting one.

[00:32:59]I've not heard of that. I I would definitely be cautious before engaging with that organization.

[00:33:06]>> Sooner or later, these things are are going to rise to the top of public consciousness one way or another. The subtitle of your book refers to the marriage of artificial intelligence and synthetic biology. And of of course that evokes the the notion of of the android which has been discussed extensively in PK Dicks novels for example and it looks frightening the idea that people will sooner or later want to have humanoid like robots as their slaves. just to just to be clear that you know that that's not a topic that I address because I'm only interested in natural biology and not not the kind of convergence of technobiology where or you know or or any kind of cyborgs or you know I mean I you know and I'm also I don't actually philosophically myself believe fundamentally that we we would want to change human nature as it is other than to get rid of disease and to increase healthy longevity. Right now there is a case to argue that actually AI is advancing at such a rate that in another 10 years or let alone a 100red years I mean hard to imagine where AI will be in 100 years but let's take a 100 years right because I think we can all imagine based upon what's happened in the last 3 years right that in a 100red years we're going to be dealing with super you know artificial super intelligence which is a level of intelligence that will make you and I look like, you know, have the intelligence of a equivalent of a gnat, you know, like a mosquito, right? You know, and what do we do with mosquitoes?

[00:34:55]We we swap them, right? That what do you know what I mean? I don't I don't deliberately tread on ants, but what do most people do? They they crush ants with their feet, right? So, you know, if you were a super intelligent AI and you had these little mosquitoes called humans buzzing around you, right? you know, would you really be bothered with them too much, right? What would they really be adding, right? What would you and I be able to add to the debate of a super intelligent AI being, right? And and so what what I'm saying to you is that it may actually become the case that the argument as to whether or not we should augment our intelligence, memory, and so on so forth becomes irrelevant in a sense that um there is no debate because if we don't do it, we're just we're going to be consigned to the kind of dustpin of you know, intellectual history in the sense that, you know we're going to be like those old computers that used to take up three floors of a building, right? To to perform a simple calculation, right?

[00:36:04]that you know that will become irrelevant. You know, we'll be totally superseded by intelligences that outstrip us to such an extent that you know so so so it may be the case that we we're forced into a situation where we have to consider augmenting our ability simply to maintain our relevance in a world where our natural intelligence is dwarfed by artificial intelligence.

[00:36:32]right now. I'm I hope that doesn't happen, right? And it's not what I'm advocating and it's not what I aspire to. But look, I'm a very pragmatic, reasonable, open-minded person. And therefore, I wouldn't categorically rule rule out the possibility that one day humans may have to consider doing that. And if anybody's watching this in the year, you know, 2126, then, you know, I wish I knew the answer. You know, by now, you know, where where the humankind will be, right? But but hey, you know, that may become a kind of existential necessity just to kind of maintain our ability to to continue existing, right? So, let's not rule it out entirely. I'm never dogmatic. I'm always open-minded. But as of today, my view is pretty clear that I kind of like human nature. I mean, with all of its problems, you know, and there are a lot of problems, you know, violence and all the all the jealousy, you know, all all the things that uh irrationality, you know, all the things we dislike about ourselves, right? Aggression, you know, but at the end of the day, it's that paradoxical mix of good and bad that makes us human. you know the the French philosopher Voltater without getting too kind of philosophical but he he said that um that you can only appreciate the light in a painting if there is darkness right so it may be that this this primordial tension between good and bad good and evil is an insoluble paradox right that you can never get rid of evil because if you get rid of bad and evil then You can never really have good or some aspects of good will be diminished, right?

[00:38:28]Because if you think about it, some of our worst characteristics, right, have their roots in in good characteristics like ambition is is is kind of based in the desire to and our imagination to imagine a better world, right? that sometimes ambition becomes pathological and and people do things that are really unethical uh because they're ambitious. You know, it it kind of gets out of control, right?

[00:38:58]But ambition itself is not a bad thing, right? You know, it's getting that balance that ying and yang, you know, without sounding, you know, kind of, you know, too oriental here, but, you know, it's getting the balance between those things right, which matters. But you know and it's that old religious theme of you know if God is good and created the world you know with omniscience and omnipresence and all that why is there evil in the world and people say well man disobeyed God he ate the apple you know but but actually maybe it's more fundamental than that that actually there has to be evil in the world in order for good to exist and it's a really interesting question I don't know I I have the answer to it but I think there's a lot in it that that it But it but it all comes down to balance. So what that means is that you can never create the best of all possible organisms or the best of all possible humans. You can just create one that's good enough. And and and maybe it is and here's an interesting philosophical question for the listeners. Maybe it is those very imperfections that make us human, right? And if we start becoming too rational like Mr. Spock in Star Trek, right? who can't, you know, he's totally rational, right?

[00:40:14]You kind of cease to be human in the way that we understand being human today, right? Uh now, you know, you could argue that illness has its role. You know, that that, you know, Keats wouldn't have written owed to a nighting gale if he hadn't, you know, been, you know, about to die of tuberculosis or anticipated that that might happen because in at that time everybody died young, right?

[00:40:40]But having said that, you know, it's a very romantic idea that you you maintain disease to stimulate creativity because none of us wants to be the person who gets it. All right? And actually, I don't think we do particularly want illness. But but then like I said earlier, what is a disease? Like deaf people, for example, do not see deafness in many many of them, the deaf community with a capital D not see deafness as a disease. They see it as just a different way of being. And there is a deaf culture and there's deaf literature and deaf, you know, so and there are deaf parents who want their kids to be deaf, right? But you and I may perhaps say, well, deafness isn't normal, right? It's normal to be able to hear but but actually maybe that's you know maybe we're being too judgmental there you know and and there are there are other ways there there are diverse ways of being human but that's a kind of philosophical debate right let's talk more about the single cellled organism I'm inclined to think that at least for the next decade or so the work in artificial biology will largely be restricted to the single-sellled organism That's obviously the easiest thing to compute, right? I mean, we have to start off simple, right? When you when you learn to ski, you don't go on to the double diamond run on day one. Well, you can, but you know what the outcome's going to be, right? So, what do you do?

[00:42:08]You start on the ski bump, right? And the ski bump is, you know, a virus genome or a bacterial genome. a single-sellled organism or just a you know a viral virus is is a biological entity but it's not alive right and then to get from that to a complex multisellular organism or a ukareotic organism like a yeast is the next step and you just you know we're going to be moving incrementally as our knowledge increases to ever more complex organisms and we're going to learn how to compute them to a greater or lesser extent right but to an extent that's good enough to predict you the behavior of what that genome might compute and then it may be that the only way to really know what a new genome computes is by running it right like a piece of software and and when you by running it I mean actually creating it right so you may never actually know what a new genome builds until you actually run it right and that's kind of scary too right because and that comes straight from computer theory, you know, cheuring church thesis it's called, right? And um but I believe that um eventually um we'll be able to create a kind of a map a virtual map of territory right when the when the Americans arrived uh you know first settlers arrived in America in fact there you know the America was populated by indigenous species but but in terms of territory the actual land itself was kind of unknown territory right it was the kind of map without any, you know, any kind of um detail, right? I believe that we could see biological possibility as being a kind of new frontier, a kind of unmapped terrain, uh which comprises all the different genome sequences of everything that could ever be, which includes everything that has existed, does exist, and may exist. Right? And that if we master the grammar of biology, we'd be able to literally map out that terrain and predict what's going to be there. Right?

[00:44:25]So then we can travel in that terrain and materialize wherever we like by building the genome in that particular position and have a pretty good idea of what what it would produce. Right? And that's where I think this is eventually going to going to end up, right, with this kind of real estate of possible life or possible ways of being human or possible ways of being a giraffe or possible ways of being anything, right? And and then it's for us to decide, do we do we try and build that thing, right? And and why would we want to build it, right? You know, what use will it be to us? um you know it might be that we build um you know literally a living cell phone right and I I totally believe that's possible right that we'll be able to build pretty much anything that today is made using destructive you know kind of chemical processes that cause toxic you know pollution and you know unfriendly to the environment so on so so forth I think we'll be able to do all of that using biology that biology will become infrastructure And it's just a matter of understanding biology well enough, right, that we can do that, right? Uh and then of course uh the species that have existed represent the tiniest fraction of possible species and because everything has evolved, right? We know that evolution doesn't really have an inevitable direction. So, if you were to replay the tape of life and let life evolve hundreds of thousands of times, you may never get humans on any replay.

[00:46:08]Right now, also, let's take things like um oranges, um chickens, cows, wheat, you know, maze. It wasn't inevitable that they would have evolved, right? So just imagine all the other things like that which could be tremendously useful to us which have never existed because evolution didn't discover them right imagine a crop like if maze had never happened right or rice right look how useful it is to us right so I can guarantee you that there are hundreds of thousands of cash crops out there in the mathematical world of biological possibility which we could be using today to feed people in extreme environments like deserts and whatever, right? That we never discovered, you know. So that's what I the sort of vision I have about biological possibility.

[00:47:03]>> If we're talking about crops, of course, we won't be able to uh create a firewall around an entire crop.

[00:47:11]>> It's definitely going to be difficult, right? But I think there are ways of genetically isolating those genomes by like I said recoding them and introducing weaknesses into them. But you're right, you know that once you release something into the environment, um it is going to be very difficult to control. And you know, the most extreme version of this in literature was John Windham's book, The Day of the Tripffids, right? I mean, he didn't really frame it in terms of genome writing and generative biology because it didn't exist at the time. But as is often the case, science fiction often just imagines what may be possible before it is right. And that's a great kind of disaster story where everything goes wrong and plants start killing people. And and I'm not saying that, you know, genomically rewritten crops are going to behave like triffids, right?

[00:48:07]But, you know, they might they might have effects on ecosystems which are unpredictable which we regret, right?

[00:48:14]you know and that's that's where the caution comes in. So there is a price for everything you know and there is a risk with everything and that's why before we start to do these things we need to be very confident that we know what we're doing and that we know how to manage the consequences uh that may ensue from what we've done.

[00:48:36]Right? So what I'm saying is that the bar to releasing organisms into ecosystems is way higher than storing information in DNA or making bio energy or making biioaterials because there you're not you're using biology as a technology but you're not making a living thing and releasing it right. So there are different levels of stringency and regulation uh that need to be addressed you know in different ways. I gather from your book that there's really two stages essentially to this process. One would be designing the genome of a new species which can be stored in a computer memory and and manipulated and and one can do a lot of sort of gaming through uh simply artificial intelligence within a computer memory like like the game Sims for for example.

[00:49:37]But then there's the execution the actual manufacturing of of the new life form. And from what I've learned recently, your company has licensed a a system called Sidewinder, which is very advanced in terms of the ability to actually manufacture new genomes.

[00:49:57]>> Yeah, great great question, uh, Jeffrey.

[00:49:59]Yeah. And um yeah, you're you're absolutely right that to some extent you can simulate um you know the the predicted results of uh at the moment simple you know alterations like at the level of viruses and and and bacteria but but our ability to simulate more complex organisms is very rudimentary right now. Maybe eventually we we'll get we well I think we will get better at that but right now uh you know we have a rudimentary level of knowledge but even then when our ability to simulate improves uh the only real way to know what happens when you build a genome and run it is to literally build the organism and see what it looks like cuz you know they may not be fully computable and there are levels of information like for example microbiome the bugs that live on in and inside us, you know, uh they can change the way genes behave, right? But but but um to actually boot up an organism, you know, you need to design it, you need to build it. And that's where my technology Sidewinder that we've licensed from Caltech helps because it enables DNA to be built at scale rapidly, accurately, efficiently, and at very low cost.

[00:51:18]Right? So it Sidewinder uh the technology that Genro my company has licensed kind of democratizes the ability to build DNA at scale and we've we've had several new uh advances in that recently one of which will be announced at the end of um uh April actually and and this will allow us this technology will allow us to build genomes at scale but once you've built them you need to get them into cells and then boot them up so they actually run.

[00:51:50]So it's it's not trivial uh this whole process but it's something that we're learning to do and which has without any doubt uh is something that's going to dramatically change the nature of biology. And they're going to be two kind of streams of biology. Natural biology you know generated by evolution by natural selection with no intention with no purpose. And then there's going to be synthetic biology, generative biology where humans and computers uh actually design life from first principles.

[00:52:24]One of the things you point out in your book is that whereas all natural life is based on proteins and proteins are based on amino acids, it's it's possible to envision life forms that are not based on amino acids at all, but that have other biological or or other molecular components. life has evolved to use 20 amino acids and well 22 the two rare ones and use you know DNA with the the full nucleotide bases and RNA but in actual fact you know it wasn't inevitable necessarily that you had to use DNA to store biological information we know already that there are so-called XNAs which are kind of alternative uh genetic materials that could store uh information pretty effectively and DNA is based upon this very weak bond called a hydrogen bond which works well on Earth may not work well on other planets for example and also we also know that by expanding the set of amino acids from the the natural set of 20 to uh incorporate artificial amino acids we can introduce new properties into proteins and into living things. So uh and then of course we don't even need to use amino acids. We could use other polymers and monomers or even have mixtures of amino acids and other you know and other monomers. So I think life is an open feast in a sense from a technological perspective uh nature gave us one set of components but hey there are others out there too that we will undoubtedly explore. If one were to project all of these possibilities into the future, that life on this planet, human life, uh, a thousand years from now, could be vastly vastly different from anything we can even imagine today to >> totally different. Uh, and I can't begin to predict how that would change the nature of life on Earth and elsewhere, right? But there is no doubt that that's what the future holds. Yeah, it's going to happen.

[00:54:40]>> Adrien Wolfson, this has been a very enlightening conversation. It's it's opened up to my thinking possibilities that I had just never considered before.

[00:54:52]So, I'm very grateful to be able to share your knowledge and expertise with the new thinking allowed audience.

[00:54:59]>> Jeffrey, thank you so much. It's been such a pleasure to talk to you today.

[00:55:03]Your questions were wonderful, so insightful, thoughtful. I've really enjoyed it and I hope the listeners did as well.

[00:55:10]>> Well, I'll be following your work very carefully now that I'm aware of it and look forward to seeing how things evolve in that discipline.

[00:55:21]>> Really appreciate it and you can expect a lot of changes coming your way very soon.

[00:55:26]>> Well, thank you so much for being with me.

[00:55:29]>> My pleasure.

[00:55:31]And for those of you watching or listening, thank you for being with us because you are the reason that we are here.

[00:56:03]New Thinking Aloud is presented by the California Institute for Human Science, a fully accredited university offering distant learning graduate degrees that focus on mind, body, and spirit. the topics that we cover here. We are particularly excited to announce new degrees emphasizing parasychology and the paranormal. Visit their website at cihs.edu.

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