"According to NASA's Definition of Life, I'm Not Alive" - Why Nobody Can Define Life | Dr. Kate Adamala

Nobody has ever built a cell from scratch - assembled entirely from purified molecules on a shelf - that can feed itself, grow, and split into daughter cells through its own genetic activity. Until now. Dr. Kate Adamala, a synthetic biologist and a professor of genetics at the University of Minnesota, whose lab just published a landmark paper on what she calls "spud cells," joins Craig Smith to explain what her team built, why it matters, and what it will take to go from proof of concept to a platform that could eventually replace every molecule civilization currently extracts from petrochemicals. The conversation is as philosophically rich as it is technically specific: Adamala argues that life has no magic ingredient, and that the universe itself is predisposed to give rise to it. She describes the spud cell not as a mic drop but as biology's Sputnik moment: proof that you can escape the gravity well of evolution and build lifelike systems from the ground up. The episode also covers the most alarming biosecurity question in synthetic biology right now: mirror life - cells built from mirror-image molecules that would be invisible to every immune system on earth and potentially capable of replicating uncontrollably in the environment. Adamala led the global call to pause all mirror life research in 2024, and she explains both why that research was so dangerous and why the spud cell doesn't move the field any closer to that red line. Craig also asks the question nobody else thought to ask: could AI now simulate the billions of years of molecular evolution that a primordial sea would need millions of years to complete - running a few trillion iterations computationally to find what emerges? Subscribe to Eye on A. I. for weekly conversations with the people building and deploying the future of AI.

• 0:00Speaker 00

  That just shows you that there is really no good definition of life.

• 0:03Speaker 01

  In your world, life is not clearly defined. I think NASA has a working definition, self-sustaining chemical system capable of Darwinian evolution.

• 0:15Speaker 00

  That's a fantastic definition, but according to that definition of life, I'm not alive. The fact that we don't fully understand life right now doesn't mean to me that there's something that we're unable to understand. It just means we lack data at this point.

• 0:28Speaker 01

  You can create spud cells that feed on carbon in the air. Is that what you're talking about?

• 0:35Speaker 00

  I'm mostly talking about the molecules. We need a way to make all the molecules that our civilization uses right now. If you put molecules under the right conditions, in the right environment, they will start self-assembling and the emergent property of that assembly is what we call life. It's definitely a milestone, but it's not a mic drop. We're not done. We're showing that you can escape this gravity well of evolution.

• 1:00Speaker 01

  Could you introduce yourself to listeners? Give some of your background. I know that you've been working in those area for a while. You had synels, I think they were called, before spud cells. If you could give some of that background and, as I said, state what the goal of this research is.

• 1:22Speaker 00

  My name is Kate Adamala. I'm originally from Poland, where I studied chemistry. Then I got my PhD in biophysics in Italy, in Rome. And then I moved to the States for the other half of my PhD in origin of life and biophysics of origin of life. And then I did a brief stint in neurobiology, synthetic neurobiology as a postdoc. That taught me a lot. One of the things that it did teach me is that I don't like neurobiology and I don't want to work on that. So when I started my own lab, I wanted to continue the practical applicability of research that I picked up during my neurobiology work.

• 2:07Speaker 00

  I wanted to know that my research, the things that I'm doing are actually good for something. But I was really drawn to go back to my roots to work on something as cool as origin of life, as astrobiology. So I basically wanted to combine that curiosity-driven research that I've done in my early training with the practical biomedical economical applicability of the work that I learned during my postdoc. And that led me to synthetic biology and specifically synthetic cell engineering. And the overarching goal of my research is to make biology a general purpose technology. Right now, biology is very specific.

• 2:48Speaker 00

  We can make a lot of things with biology, but there are very specific things. And general purpose technology is something that you can pick up and apply to a new direction, new application, new purpose, without the need to re-engineer the whole chassis. Like I can take my work computer and start watching dog videos anytime without having to rewrite the operating system. And that's the kind of a philosophy, that's the purpose that I want to apply to biology, to moving atoms with biology. And natural biology is not a general purpose technology and I don't think it, I don't believe it can be. Because natural biology is very complicated.

• 3:33Speaker 00

  It has a lot of dependencies that we don't understand. And that's, that led me to synthetic cell engineering. If you want to make a cell that can be reprogrammed on demand, that can be applied to whatever application you want, to making medicine, diagnostics, making molecules for bioeconomy, that needs to be a platform that's fully engineerable. And you do not have full engineerability on a system that you cannot fully describe. And that's what natural cells are. It's, they're amazing, but they're not fully describable. They're not chemically defined. And that's where synthetic cells place themselves. They have some advantages of biology.

• 4:15Speaker 00

  The fact that we can take energy and take feedstock and turn it into whatever atoms we want, whatever products we want. It replicates, it grows, it can make more of itself, so the costs go down. But we have this engineerability. We can exactly say, I want to make X pathway with Y product.

• 4:36Speaker 01

  That's fascinating. And, and so it's not, you know, in artificial intelligence, the motivating question for a lot of AI researchers is to understand or how does the brain work? What is consciousness? All of that. So in your work, it's not to understand how life begins. It's, it's, it's sort of, that's, there, there may be some insight into that, but you're more interested in how can you manipulate biology to produce products?

• 5:20Speaker 00

  Both, actually. There is a very strong curiosity-driven aspect to my research. I would really like to understand what makes molecules tick. What make, because life to me is a complex behavior of molecules. I don't think life as a phenomena has anything magical to it. I think life is just a manifestation of properties of molecules and we don't understand right now how that happened. How did those molecules became what we call alive? So there's definitely this quest to understand how non-living molecules become life. And there's also this quest to understand both healthy and diseased states of life, our own cells.

• 6:04Speaker 00

  How do we make a full model of a healthy cell, of a sick cell? How do we differentiate between those two? How we understand those processes better? And all of that, I think Richard Feynman said, what I cannot build, I cannot understand. And all of those processes of cells, everything that makes us what we are, cannot be fully understood unless we get our hands on every molecule that makes that possible. So there definitely is this foundational curiosity-driven aspect of my research. But the main, big picture motivation is that I want this planet to be habitable in 50 years.

• 6:46Speaker 00

  I want to leave, leave something, you know, I want our kids to have a world to live on. And that's not, I think that's not possible unless we switch to moving all the molecules with biology instead of dead biology, petrochemicals. So that practical aspect is the main, like everyday driver. But there definitely is that, that childhood curiosity of, of what actually life is. How do molecules make life? And those both are combined in the work we're doing.

• 7:18Speaker 01

  Yeah. And just for listeners, you know, as in AI work,

• 7:27Speaker 01

  understanding and consciousness are very amorphous terms that nobody can really nail down. And in, in your world, life is not clearly defined.

• 7:44Speaker 01

  I think NASA has a working definition, self-sustaining chemical system capable of Darwinian evolution.

• 7:55Speaker 00

  And that, that definition, that, that's a fantastic definition, but according to that definition of life, I'm not alive.

• 8:03Speaker 01

  Yeah.

• 8:03Speaker 00

  Because, yeah. And that just shows you that there is really no good definition of life.

• 8:09Speaker 01

  That's right. Although you're talking about the reproducibility, but you're, you're defining a, a single organism as opposed to

• 8:21Speaker 01

  a class of organisms. And certainly reproducibility is a feature of, of the human race. It may not be of every organism within the human race. Spud cells are not self-sustaining and they don't truly evolve. So are you leaning on the absence of a definition to keep the question open? Or, or, and you're, you're looking for a definition? Or is that beside the point?

• 8:54Speaker 00

  To me, it's beside the point because I think there is no clear boundary on the molecular level between life and non-life. I think life, life and non-life are opposite ends of a continuum.

• 9:08Speaker 01

  Just a sec, Kate, I'm sorry. Yeah.

• 9:20Speaker 01

  No, well, regard, I'm recording. I'll talk to you afterward. Okay?

• 9:27Speaker 02

  Of course. Apologies, sir. Won't happen again. Carry on.

• 9:31Speaker 01

  I'm sorry, Kate. Go ahead.

• 9:34Speaker 00

  To me, it's beside the point because I think there is no clear boundary on the molecular level between life and non-life. I think life, life and non-life are opposite ends of a continuum. There's a spectrum of complexity, spectrum of organization. And we can see that even in our kind of instinctive definition. If you look at a human, if I, you know, if if someone cuts off my head, I will immediately become dead by any medical, legal, human definition. But most of my cells will keep going for quite a while. And the cells in my gut, the cells that make me but are not me, the bacteria in my gut will keep going happily

• 10:17Speaker 00

  long after the the legal me is dead. And that that just shows you life is not a strict definable phenomena. And I love those discussions for fun over beers, but it's not a scientific problem that we're really that we really need to solve, or I don't think it's even solvable.

• 10:42Speaker 01

  What's fascinating about this work is that you have created, and and I'll ask you to, I've read the paper, I've read a lot of the articles about the paper. If if you can give us kind of a a brief, give listeners a brief for what has happened. You have this mixture of purified chemicals or molecules. And you have this mechanism that forms a lipid bubble around them. And then you you can introduce

• 11:18Speaker 01

  nutrients and ribosomes that then can can work on the DNA in the inside the the cell or what you're calling a spud cell. Can you just describe what exactly is going on in in in simple terms? And those that want a deeper explanation can read the paper?

• 11:47Speaker 00

  I think you described it really perfectly. So what we have is a mixture of purified defined molecules. And those molecules are derived mostly from living sources. They're bacterial proteins or proteins from other sources that were expressed and purified from bacteria. And they're small molecules that, you know, to me, they come from a shelf, from a bottle on a shelf. And they end up in that bottle because someone purified it from mostly a natural source. So they're all biologically derived. And we mix those molecules at certain concentrations under the right pH in the in the right solution.

• 12:28Speaker 00

  And they start rebuilding some of the elements of life, the translation, protein translation, metabolism restarts when you put those molecules together at the right conditions. And then we take this, we load it up with a genome, so a DNA plasmids that contain the genes that we want our cells to have. And then we stuff all of that into a lipid vesicle, so lipid bubble. That's very much like the membranes of natural cells. And that's what a spud cell is. And what happens once we start that experiment is that the spud cell is capable of feeding. So it eats nutrient-rich little liposomes or exosomes.

• 13:11Speaker 00

  And then it can also divide. It can make daughter cells. It's always daughter cells for some reason. It's never son cells.

• 13:19Speaker 00

  It makes a whole bunch of little daughter cells.

• 13:21Speaker 01

  Yeah, although that part is an external mechanism that you apply to the spud cells. It doesn't, I mean, I understand it grows with the nutrients. It absorbs these these nutrient bubbles. They fuse into the skin of the of the spud cell. And so the skin of the spud cell grows, those nutrients then are mixed into the inside of the cell and metabolized.

• 14:00Speaker 01

  But when when the cell is grown to a size that it it you want it to split into two cells, you do that mechanically. That's not a natural process.

• 14:14Speaker 00

  No, the the part of the paper, the results in the first few figures are with mechanical division. But then the later in the paper, we have genetically encoded division. And I think every figure is is labeled which one is mechanical and which one's genetically encoded. There there is a genetically encoded division, and that's why people get excited about this, because this is the first example of not only genetically encoded feeding, but also genetically encoded division. There is a mechanism where a spud cell expresses a protein, and that protein goes to the membrane and pokes its head out of the membrane. And when that protein is present,

• 14:57Speaker 00

  it recruits a giant protein from the environment that induces curvature of the membrane, and that leads to division. So even though the giant protein come from media, their recruitment, which is the key step to bring that protein and start division, comes from the genetic activity of the spud cell itself.

• 15:17Speaker 01

  This is a little bit off topic, but it's something I wondered for a while. You know, Michael Levin, who does the

• 15:26Speaker 01

  yeah, the work with the flatworms?

• 15:28Speaker 00

  Yes.

• 15:29Speaker 01

  I I saw him speak years ago. And it's he manipulates the electrical field inside and outside and between

• 15:43Speaker 01

  organelles or whatever they're called inside the flatworm with different

• 15:50Speaker 01

  solutions, different with different pHs and is is that happening inside a spud cell? Is there is there any manipulation of the electrical activity? Or is this purely

• 16:09Speaker 01

  something else?

• 16:11Speaker 00

  It's purely something else. We do not right now rely on electrical activity. I wish we did. It's one of my on my wish list to make spiking synthetic cells that have electrical potential that we can manipulate. But right now, there is no electrical activity that that we manipulate across the membranes.

• 16:33Speaker 01

  Yeah. And and from what I understand as well, the the the two most critical elements spud cell needs to replicate its or to to grow are the ribosomes and the transfer RNA. Right? And you introduce those from E. coli bacteria. Is is that right?

• 17:01Speaker 00

  Correct. We purify, we purify those from E. coli and then feed it to the spud cell.

• 17:06Speaker 01

  And what would it take? Obviously, this must be on on your wish list, wish, wish list? Or

• 17:17Speaker 01

  roadmap?

• 17:20Speaker 01

  I understand that it's very complicated and and you want, that's not the problem you're working on. But how would you create the DNA to inside the cell to build its own ribosomes or transfer RNA?

• 17:44Speaker 00

  That's a great question. That actually is a problem we're working on. This is my personal next big step that I want to work on is how do you make ribosomes? Introducing the DNA that we need to make ribosomes is actually not a big deal. We can express all of the proteins that we need to make a make a ribosome and make all the trnas. The problem is, though, that if we express all those proteins, put them together, they do not form an active ribosome. And nobody knows why.

• 18:21Speaker 00

  And that's, to me, right now, if you ask me to name single, there's there's many. But if you if I were to pick a single biggest mystery that we need to solve in in bioengineering, I would say this process called ribogenesis, how do you make new ribosomes? Is on absolutely on top of my list. We can put together all the proteins, and that's been done before. And those proteins, unless you really coax them with a lot of external help, they will not even approximate an active ribosome. George Church's lab demonstrated a few years ago now that it's possible to take all of those purified proteins. And under very special conditions,

• 19:04Speaker 00

  once you purified all of them, you can put them back together and some ribosomal activity will be detected. But it's not a robust process that you can do as you're expressing them inside a synthetic cell. And I think we're missing something. We're missing either some protein, some small molecule, or some environmental factors. And that's what my lab is working on right now.

• 19:25Speaker 01

  There are two directions you can attack this from. You're doing bottom up, where you take the purified molecules, mix them in in very precise quantities or ratios, and they start interacting. I was asking about the electrical potential. But I mean, what starts them reacting? Maybe you can talk about that. But the the ribosome, the other way to attack this is by taking a living cell and and removing as much as you can and still have it active. I think that was done

• 20:11Speaker 01

  you know, in 20 years ago or something.

• 20:15Speaker 00

  That was on my Craig Ben 30s.

• 20:17Speaker 01

  When you look at a ribosome in a living cell, are there any insights into how that is forming? Is it? Is it being constructed?

• 20:31Speaker 01

  Are the instructions for building ribosomes in the DNA? They must be.

• 20:38Speaker 00

  Yes, and the the way it happens in in living cells is that it happens in stages as those proteins and RNA are being made. So it's not like everything is first made and then staged and then assembled. It's being assembled as you're making it. And I think this is the step we're missing is we don't know exactly in what order those things need to be assembled, but we do know that you can't just let it all wait there, sit and then assemble. You have to keep assembling it as as it's being made.

• 21:13Speaker 01

  These are artificially

• 21:17Speaker 01

  created. Do I call them vesicles? What do I call them?

• 21:21Speaker 00

  Vesicles is what we call them, yeah.

• 21:23Speaker 01

  Vesicles, okay. That have nutrients and and the ribosomes and tRNA inside them.

• 21:36Speaker 01

  And that fuses with with the outside of the cell, but it fuses locking onto a docking tag that is expressed from within the cell. That fascinated me that it's that the cell does create the mechanism, even though you're introducing artificially

• 22:03Speaker 01

  created vesicles that have this material in it. The the the fact that it can fuse with the spud cell is a function of the spud cells DNA or internal mechanisms, right?

• 22:20Speaker 00

  That's correct. The feeding is induced by basically the cells' ability to express the proteins that ask for food. So it's like a little bird opening his mouth. It's that's what the spud cell is doing essentially.

• 22:35Speaker 01

  Can you talk about? Is this purely atomic bonds being formed between molecules? I mean, what is the the spark that starts all of this happening? That a lot of people ultimately would call life? That it starts happening spontaneously if you put all of these molecules in the right

• 23:04Speaker 01

  quantities in in close proximity?

• 23:09Speaker 00

  That's the beauty of it. It starts happening because of the properties of those molecules. And that's why I said earlier that I don't think there's anything special about the phenomena of life as as a I think it's a property of molecules. If you put molecules under the right conditions in the right environment, they will start self assembling and the emergent property of that assembly is what we call life. There is nothing special about a spud cell or really any other cell that does not come from properties of atoms that make it. And the fact that we don't fully understand life right now doesn't mean to me that there's something that we're unable to understand.

• 23:53Speaker 00

  It just means we we lack data at this point. Which on one hand, you might think it's kind of a lax, the the mystery and romance of of what life is, but to me, that is the ultimate romance. That is the ultimate mystery. Because that means the universe is posed to give rise to life. The exact physical chemical conditions of the universe enabled creation of the molecules that eventually are predisposed to become life. That's to me, that that doesn't get more magical than that.

• 24:24Speaker 01

  How does a real of a living cell feed? Is it through a similar mechanism, these protein tags that capture?

• 24:34Speaker 00

  It depends. The process that the spud cell uses to feed is very similar to phagocytosis. It's a process that where a cell kind of engulfs a piece of food, another cell, or it could be an exosome. And that's one process of feeding. Most cells either if they're predators, they feed by basically engulfing another cell. Many other cells feed by just uptake nutrients, molecular nutrients directly from the environment. Spud cell does that too through its membrane pores. There is an optimized growth solution for it. So it's one of the mechanisms.

• 25:15Speaker 01

  Mutation that you introduced allowed some spud cells to feed more aggressively and grow larger and eventually outcompete the smaller ones. That mutation was introduced to the DNA, is that right?

• 25:34Speaker 00

  Yes, by by me artificially. I I wanted to clarify, yes, we introduced those mutations artificially. And that's why I claim that spud cell is not capable of evolution right now. Even though it is capable of selection, if you give it a better mutation, that mutation will win after a few generations, but I have to give it that mutation. It doesn't arise spontaneously. So that's why to me, that's not evolution.

• 26:00Speaker 01

  Cells are dividing, whether or not it's mechanically or or internally triggered. If they're dividing, I mean, you were saying in the paper that about only about thirty percent of the divided cells, the daughter cells, carried complete DNA. Is it possible if? I mean, mutations are errors in the replication of DNA. Is it possible if you did this at some monstrous scale that you would start seeing spontaneous mutations?

• 26:37Speaker 00

  Absolutely. I think if you scale it up enough, you would start seeing spontaneous mutations arising in that population. It's not a mechanism we can rely on right now, just because we don't have infinite resources and infinite volumes. That's why I would like a better evolvability, better evolution mechanism.

• 26:57Speaker 01

  So the evolution, you're inducing it, but that doesn't mean that it wouldn't happen naturally if this

• 27:06Speaker 01

  were in a primordial sea, you know?

• 27:11Speaker 00

  Yes, if you had the scale, if you had the volume of a primordial sea and a few million years, it would totally start evolving. It just, you know, my I work on the scale of a page length of the PhD, not length of the primordial evolution. So we can't really wait quite that long.

• 27:29Speaker 01

  Is it possible now with these increasingly powerful models to to run this computationally and see what happens after? You know, a few trillion iterations?

• 27:44Speaker 00

  I think it's absolutely possible. We're working with some collaborators to develop that model to you basically in in order to, as you know, way better than me, in order to get anything useful out of AI, the quality of your training data has to be really top notch. You have to have a lot of high quality, clean training data. So that's what we're working on right now is is making models that will help us speed up that iteration and evolution process a little.

• 28:14Speaker 01

  You're working toward this goal. Was the spud cell surprising to you, the the success of this? Or have there been so many iterations that you finally got to this point? And it's incomplete? And there are a lot of things that it doesn't do, but at least you're here and and it's just a milestone on a long road. I mean, how do you feel about what what you've done with spud cells?

• 28:42Speaker 00

  I feel incredibly proud of our team and I feel very happy that we got it to this point. I feel both surprised and not. I'm surprised because I'm always surprised when experiments work. There's so many failed experiments in this field, like in any experimental science, that when something finally works, it is in a way a pleasant surprise. But I'm also not surprised because we designed it to work. We built the whole thing from scratch. And it's definitely a milestone, but it's not a mic drop. We're not done. We're not going home yet. It's the

• 29:22Speaker 00

  big milestone that shows what's possible. That's why we're making naming analogies to Sputnik. We're we're showing that you can escape this gravity well of evolution. You can put molecules together into a system that starts making lifelike noises. But it's not a complete system and it will not hopefully ever be completed. I think this is a platform that will always be changing, that will always be evolving into something better.

• 29:51Speaker 01

  You were saying at the beginning that, well, certainly understanding how life arises from from molecules is is, you know, one of the goals. The other is to create this kind of chassis on which you can biology as as a workhorse for for in medicine or material science.

• 30:20Speaker 01

  Today, the spud cell does a marker protein, and you call it a glowing marker protein. First of all, what does a glowing marker protein mean?

• 30:32Speaker 00

  It's a fluorescent protein, so a glowing, as in it makes fluorescence. It's a GFP. It's that workhorse of synthetic biology, a green fluorescent protein originally from jellyfish.

• 30:44Speaker 01

  So the fact that you can, that the spud cell can make this,

• 30:52Speaker 01

  how big a jump is from that to it making a useful protein drug like insulin?

• 31:02Speaker 00

  It's quite a bit of a jump, but less than it seems like. It's insulin in particular, it's tricky because you have to post-translationally process it. Other drugs will probably come first. High-value drugs that use different building blocks. There are some antibiotics, there are some protein therapeutics that use amino acids that are not canonical, so not one of those 22 amino acids that organisms put into proteins. And spud cell right now could be programmed to make most of those. The bottleneck in scaling that up so it actually becomes a useful therapeutic

• 31:44Speaker 00

  is the spud cell's inefficient replication. Because programming it to make something is relatively easy. Programming it to make something at scale is hard. And you're not going to make money on a drug unless you learn how to do it at scale. And that's why we're pushing for better metabolism for replication now, because that's what really is going to enable applications.

• 32:12Speaker 01

  And the idea is, so it's not actually expressing the protein inside the cell? It's having the cell reproduce efficiently? And is that right?

• 32:28Speaker 00

  That's the bottleneck, yes. That's why our discovery is so significant, because we show that it's possible to make those cells grow and replicate. And now the big goal is to make them grow and replicate robustly, enthusiastically, I would say.

• 32:44Speaker 01

  And then you could have the plasmids or the DNA inside the cell expressing a drug protein of some sort?

• 32:57Speaker 00

  That's correct. That's the goal.

• 32:59Speaker 01

  And then you would, what would you do? You would have a vat of spud cells, and then you would dissolve the liposome exterior, and you'd be left, you know, separate what's left, and you would be able to purify. Wow, that's...

• 33:17Speaker 00

  Or you could convince, even easier, you could convince the potato to give out its product. The spud cell could be programmed in a way that it would secrete the product into the media, and then it would be much easier to separate it.

• 33:32Speaker 01

  I see, yeah, yeah.

• 33:35Speaker 01

  So plastics and materials are very different

• 33:43Speaker 01

  because there's a whole multi-step enzyme

• 33:50Speaker 01

  string of interactions that need to take place, not just one gene expression. Has anyone shown that's feasible in a system like that? Or is this just conceptual?

• 34:05Speaker 00

  People have shown that polymers can be made in that cell-free system. That's the cytoplasm of spud cell. As far as I know, nothing of economical value has been expressed in a synthetic cell yet. But that might mostly be because we haven't had the thing grow and replicate. So scaling it up is just ridiculously expensive.

• 34:27Speaker 01

  And what do you think about, I mean, from what you understand so far, what do you think led to life? I mean, as you said, maybe it's not as mysterious as people have historically thought. Do you think that the conditions were correct on Earth? There are all of these chemicals and, you know, molecules in the air and in, you know, the water or whatever medium was covering the Earth, and that these molecules just spontaneously found each other

• 35:12Speaker 01

  and started interacting? And then grew a membrane as protection or something? And that it just, it just happened that way? Rather than there being, as I said, some, I don't know, I guess we're all thinking of Frankenstein, you know, the lightning coming down, I mean, some electricals.

• 35:37Speaker 00

  I think definitely electrical impulses helped with the origin of life processes because they gave energy for certain reactions to happen. But that's still a property of matter. The fact that we had an atmosphere that was capable of producing electric discharge is a property of matter. It's a property of that atmosphere.

• 35:56Speaker 01

  Yeah, yeah.

• 35:57Speaker 00

  I'm sorry to take the magic out of it.

• 36:00Speaker 01

  No, it's, that's what I love about this. I mean, that's what's, as you said, it's still magical. It just is understandable. Your paper argues that a spud cell can't survive outside the lab because it needs chemicals it would never find in the wild. It's a milestone toward evolvable autonomous cells that could find the things it needs, the chemicals it needs in the wild. I mean, presumably you could, so that it could use chemicals

• 36:42Speaker 01

  that are not purified or that exist in nature.

• 36:48Speaker 00

  That's the goal, yes. I hope that we will be able to get spud cell to the point when it is capable of autonomous survival in the environment. That's what we need to rescale up this technology.

• 37:01Speaker 01

  Yeah, and you talk about in the paper the safety issue. And actually, a couple of years ago, you led the call to pause a mirror life research, which I was not aware of until I started reading your stuff.

• 37:26Speaker 01

  And you see the, you link spud cells to that debate. I mean, so does the spud cell move the world closer to mirror cell capability?

• 37:43Speaker 01

  And if it does, how do you, how do you prevent that?

• 37:48Speaker 00

  I don't think spud cell moves us closer to any red line on mirror cell research because spud cell does not use any mirror enantiomers. It uses all the normal, natural enantiomers of all the building blocks. And that's the big bottleneck in making a mirror cell, and I hope it remains a bottleneck, is that we just don't have the building blocks for it. So a spud cell doesn't, to me, doesn't count as an enabling technology for mirror life because it doesn't make us any closer to solving this big problem of where the hell do we get a bucket of mirror ribosomes? We don't have a source right now, and I hope we never do.

• 38:32Speaker 01

  Yeah, and just to explain to listeners what mirror life refers to.

• 38:39Speaker 00

  Every molecule exists in two different forms. Every biological molecule can have those two forms that we call enantiomers or isomers. There is the one form that all life uses, and then there's the other form, which is literally a mirror image of that molecule. And life set on using DNA, RNA, and proteins of a certain enantiomer, a certain form. So we had this idea that if we take all the same molecules but of a mirror enantiomer of natural molecules, we could put together a whole cell that's made of those mirror molecules. And we know that those mirror molecules interact with each other the very same way that natural molecules interact with each other.

• 39:25Speaker 00

  They can, the enzymes can recognize mirror substrates, mirror proteins, recognize mirror DNA. So you could have this whole mirror biology world. And we wanted to do it because we hoped that there would be no cross-talk between natural and mirror biology, that we could make drugs that are not recognized by immune system. So you could treat a patient without immune response. And we also hope that you could have bioreactors, so means of producing things with biology that cannot be contaminated by an environmental pathogen or a phage or virus because that mirror biology is kind of insulated from natural biology. And as we contemplated the consequences of that

• 40:09Speaker 00

  and started actually experimentally working towards that, other people, immunologists and environmental biologists, pointed out that if you have an organism that could possibly be so stealth, then you don't want to have that organism because it could basically fly under the radar. It could replicate in the environment uncontrollably. And that's what led us to this big biosafety and biosecurity analysis of mirror life. And we concluded that, as cool as it sounds to make a mirror cell, it should never be done because there is no way to do it safely.

• 40:43Speaker 01

  What happens to all these mirror molecules in nature? Are they in inanimate objects? I mean, what, they exist naturally, is that right?

• 40:55Speaker 00

  Some of them exist naturally, but not many of them. Most of the molecules, complex biological molecules that we find in nature right now come from biology. And biology is very peculiar about which of those forms, which of those enantiomers it wants to use. And it doesn't let much of the opposite one to exist, which is why I said we don't really have a source of the mirror enantiomers to build a cell. That's why spud cell is not really solving this big problem because it's not giving us an abundance of the opposite corallium, the opposite enantiomer molecules.

• 41:33Speaker 01

  Is that research stopped now since the...

• 41:39Speaker 01

  Your movement in 2024?

• 41:41Speaker 00

  Yes, um, as far as we know, all that big research initiatives all over the world that were aiming at building mirror cell or technologies that can lead to mirror cells have stopped.

• 41:54Speaker 01

  Got to ask again, since I'm so focused on AI.

• 41:59Speaker 01

  You know, anthropics mythos model that

• 42:04Speaker 01

  that is has not been released publicly. They've released the Fable five model, which is supposedly safer. But I was using Fable five to understand parts of your paper and it it would downgrade to Opus four point eight. It would not allow me to use Fable five, presumably because of these safety concerns, but now there are open source models that are as powerful uh, coming out of China. Is it possible for

• 42:37Speaker 01

  people to use those models to understand mirror molecules or how to create them?

• 42:45Speaker 00

  It's definitely possible to use the models um to understand those molecules. Um, understanding the molecules is not going to get you any closer to mirror life, though. You still have to physically get your hands on those molecules and that's luckily a really difficult uh thing to do.

• 43:06Speaker 01

  Yeah, yeah.

• 43:07Speaker 00

  Luckily for us.

• 43:08Speaker 01

  Let's just uh finish up then with uh spud cells. What what is, what are the safety concerns with spud cells? If you uh manage to have them self replicate robustly, if you manage to have them uh feed robustly.

• 43:29Speaker 01

  As you said, right now, they wouldn't exist outside of the lab, but if they could uh use uh molecules discovered in nature, is the concern that they you would not be able to stop them replicating then?

• 43:48Speaker 00

  No, because spud cells are made of the same molecules that the rest of biology. So they are susceptible to everything else that the rest of biology is susceptible to. You can treat them with antibiotics. You can build um those mechanisms into them that stop their replication. If they find themselves in the wild, if that's what you want. They can also be recognized by immune systems and they can be eaten, just plain eaten in the environment. They they can be attacked by predators. They can be infected by viruses. So all the safety and security concerns with spud cells are the same as with the rest of bioengineered natural biology. So if you're making an yeast strain or a bacteria strain for bioengineering,

• 44:33Speaker 00

  all the same concerns, containment and safety, security concerns apply to spud cells.

• 44:39Speaker 01

  Final question, do you do you expect quote unquote engineered life to uh to be achieved in in your uh career?

• 44:49Speaker 00

  I sure hope so. That's kind of I'm betting my whole career on that. I I think we have to, we as the civilization have to have engineered life because otherwise we're not going to keep our way of life, keep our civilization unless we find a way to engineer biology to make all the molecules that we need.

• 45:09Speaker 01

  And and the reason is, for example, uh global warming and and uh

• 45:17Speaker 01

  you know, you need something, I mean, carbon capture, for example, you could create uh spud cells that that feed on carbon in the air or something. Is that what you're talking about?

• 45:30Speaker 00

  Yes, I'm mostly talking about the molecules. We need a way to make all the molecules that our civilization uses right now and we we cannot keep getting them from oil. And then, you know, we can stop the climate change and then we can start working on reversing it, on mitigating the effects. But we absolutely have to do it because if we don't, then we're just screwed. There is no way for this civilization to continue, for people to have the lifestyle we do and enjoy and keep the planet habitable.

• 46:03Speaker 01

  Okay, well, I'll leave it there.