Building Life from Scratch with Kerstin Göpfrich

What is the origin of life in the universe? Neil deGrasse Tyson and Matt Kirshen explore how life got its start, the Miller-Urey experiment, and synthetic biology with molecular biologist Kerstin Göpfrich. Could the first alien life we find be the one we make?

Speaker names marked ? are inferred from speaking time and the show’s known hosts — they are not voice-verified.

• 0:00Neil deGrasse Tyson?

  So Matt, she's making aliens in the laboratory.

• 0:03Matt Kirshen?

  She is the puppet master. She's the, she's the new creator of the universe and it's quite terrifying. But fun, it's informative, but terrifying.

• 0:10Neil deGrasse Tyson?

  Scientifically enlightened, I would say.

• 0:12Matt Kirshen?

  Very.

• 0:13Neil deGrasse Tyson?

  Coming up on StarTalk.

• 0:17Neil deGrasse Tyson?

  Welcome to StarTalk, your place in the universe where science and pop culture collide. StarTalk begins right now.

• 0:30Neil deGrasse Tyson?

  This is StarTalk. Neil deGrasse Tyson, your personal astrophysicist. I got with me today, Matt Kirshen. Matt, welcome back.

• 0:38Matt Kirshen?

  Thank you so much, Neil. It's good to be back.

• 0:40Neil deGrasse Tyson?

  Yeah, it's been too long.

• 0:41Matt Kirshen?

  It's been a while. It's nice to be back in New York in the office. It's great.

• 0:44Neil deGrasse Tyson?

  But where are you based?

• 0:45Matt Kirshen?

  I'm in LA. I'm still in LA.

• 0:46Neil deGrasse Tyson?

  Oh, you're a LA guy. I knew that. I knew that.

• 0:48Matt Kirshen?

  Yeah, it's nice to be back over on this coast.

• 0:51Neil deGrasse Tyson?

  So we nab you every time you slip by.

• 0:53Matt Kirshen?

  Anytime I'm anywhere near, I will, I will hit your people up and.

• 0:57Neil deGrasse Tyson?

  And now you're on tour, apparently. Oh, my God.

• 1:00Matt Kirshen?

  Yeah, well, I'm on two sort of, so I'm touring at the moment with, opening for Sarah Millican, who's a great UK comic. So I'm doing lovely theatres with her.

• 1:08Neil deGrasse Tyson?

  Through the States.

• 1:08Matt Kirshen?

  She's doing the US and then I'm also doing my own headlining spots, kind of off the back of those shows. So I'm like, hey, loads and loads of people, if you enjoyed me for 15 minutes in this massive room and want to see me do a headline show in a significantly smaller room, then, so yeah, I'm doing those. So, yeah.

• 1:25Neil deGrasse Tyson?

  Okay, cool. So we can find you mattkirschen.com.

• 1:28Matt Kirshen?

  mattkirschen.com. Yeah, all the tour dates and the links are up there.

• 1:32Neil deGrasse Tyson?

  Very cool. Such a big fan of comedians. Thanks for, thanks for being a part of civilization.

• 1:37Matt Kirshen?

  Oh, well, I've never heard it put like that. That is a, that is a much deeper way than I've ever had my job described before. And I love that.

• 1:43Neil deGrasse Tyson?

  Tell your parents that too, in case they were wondering.

• 1:46Matt Kirshen?

  Mom, Dad, you know that degree that I did nothing with and then ran off to join the circus? Well, I am a, I am a deep part of civilization.

• 1:53Neil deGrasse Tyson?

  Exactly. There you go. Well, today's topic, oh my gosh, oh my gosh. We're talking about making life.

• 2:03Matt Kirshen?

  Yes.

• 2:04Neil deGrasse Tyson?

  From scratch.

• 2:05Matt Kirshen?

  Speaking of parts of civilization or.

• 2:08Neil deGrasse Tyson?

  Making life from scratch, which technically would be alien life, if you think about it that way, right? I mean, it was life that has never existed on Earth before.

• 2:18Matt Kirshen?

  Yeah. What are the rules? Cause if it's made from scratch on Earth, is that alien or what?

• 2:22Neil deGrasse Tyson?

  I don't know.

• 2:23Matt Kirshen?

  I guess we're getting into immigration questions now.

• 2:28Neil deGrasse Tyson?

  Illegal aliens or legal aliens?

• 2:30Matt Kirshen?

  Yeah, is there birthright laws for?

• 2:32Neil deGrasse Tyson?

  If you make them in the United States, they're native to America.

• 2:35Matt Kirshen?

  Right, right, all right. Or if you make them on an army base in another country, then I don't know. Like, what are we doing here?

• 2:41Neil deGrasse Tyson?

  So I don't have sufficient expertise on this.

• 2:44Matt Kirshen?

  Yeah.

• 2:44Neil deGrasse Tyson?

  And as, as what we do on StarTalk is find the expertise wherever it is. And that took us to Heidelberg.

• 2:52Matt Kirshen?

  Nice.

• 2:53Neil deGrasse Tyson?

  My gosh.

• 2:54Matt Kirshen?

  Beautiful city.

• 2:55Neil deGrasse Tyson?

  Join me in welcoming Kirsten Goprich. Did I pronounce that correctly?

• 3:01Speaker 02

  Excellent. I'm very excited to be here.

• 3:04Neil deGrasse Tyson?

  That was two thumbs up.

• 3:05Matt Kirshen?

  Two thumbs up, two thumbs up.

• 3:08Neil deGrasse Tyson?

  Kirsten, thanks for agreeing to this conversation. You are professor at the Center for Molecular Biology at Heidelberg University. Love it. And you led the Max Planck Research Group in Biophysical Engineering of Life. Ooh. Now, just remind me, because there's a Max Planck Institute for Astrophysics. So there are Max Planck Institutes for many different branches of science, correct?

• 3:37Speaker 02

  Indeed, there is, there's more than 80 Max Planck Institutes across Germany and abroad, actually. Yeah.

• 3:42Neil deGrasse Tyson?

  I didn't know there were even that many. Max Planck is basically birth quantum physics.

• 3:47Matt Kirshen?

  Right.

• 3:47Neil deGrasse Tyson?

  With a paper he published in 1900 saying, hey, wait a minute. Maybe energy is not a continuum. Maybe it comes in quantized amounts.

• 3:58Matt Kirshen?

  And so he, we consider the father of?

• 4:00Neil deGrasse Tyson?

  Well, he, but he just.

• 4:01Matt Kirshen?

  One of the fathers of quantum physics.

• 4:03Neil deGrasse Tyson?

  He planted this seed that completely blossomed a century ago. Like Max Planck. And he's duly honored in all of these institutes throughout Germany. You got your PhD at the University of Cambridge and where you were a Marie Curie Fellow in synthetic biology.

• 4:20Matt Kirshen?

  Wow.

• 4:20Neil deGrasse Tyson?

  That means you, you are, you are Dr. Frankenstein, creating life in a laboratory. Is that, have I mischaracterized you in any way by calling you that?

• 4:33Speaker 02

  I'm not Dr. Frankenstein. No, and that's not our aim. Our aim is really to, to create a synthetic cell from the bottom up. So to achieve a transition from matter to life in the laboratory. That's, that's right. Yes.

• 4:45Matt Kirshen?

  So just to be clear, you don't have to wait for lightning to strike the lab before?

• 4:49Speaker 02

  No, not, not really, not really.

• 4:53Speaker 02

  And we are also doing it with the best intentions, I have to say.

• 4:57Neil deGrasse Tyson?

  The lightning is metaphor for an energy source.

• 5:01Matt Kirshen?

  Right.

• 5:01Neil deGrasse Tyson?

  That would then infuse the life form. So why don't we just start from the beginning? Do we have a sufficiently good definition of life? For us to then know the moment you may have created it?

• 5:15Speaker 02

  Yeah, so there's many definitions of life out there, right? And there's not really consensus on one, but I would say in my field, bottom up synthetic biology, what we really use as a working definition, and you'll be happy to hear this, Neil, is a self sustaining chemical system capable of Darwinian evolution. And that definition was put forward by the NASA. And we extend it, we don't just want a system capable of Darwinian evolution. We actually want a system capable of open ended evolution. So it can essentially increase itself in complexity. It can evolve to perform any desired task in the end. So that's what we are after.

• 5:56Matt Kirshen?

  So what's the, sorry, what's the difference between Darwinian evolution and open evolution?

• 6:00Speaker 02

  So Darwinian evolution can be, there can be open endedness in Darwinian evolution. So what we are really after is a system where the evolutionary landscape is large enough so that at any given time, the number of genotypes only exploit a sufficiently small, small space on that evolutionary landscape, so to say. So there's really, there is really a lot of space to introduce serendipity, to introduce changes, to introduce, well, also some kind of emergent properties that are inherent to living systems.

• 6:39Neil deGrasse Tyson?

  So Darwinian would presume that the change is favored only for the survival of the organism? And you're suggesting there might be forces operating that just simply change the organism without reference to its survival? Is that a fair way to think about open ended evolution?

• 6:55Speaker 02

  Yeah, well, yeah, to essentially, to essentially go for systems that increase in complexity and do interesting things. So that's what we are after.

• 7:02Neil deGrasse Tyson?

  So if an organism never dies or lives sufficiently long, then it can't undergo Darwinian evolution?

• 7:10Speaker 02

  So on the population level, I think introducing death into into living systems is absolutely crucial because otherwise, you know, you just have exponential growth and the resources will be exploited.

• 7:25Neil deGrasse Tyson?

  I'd never heard anybody say that before. We have to make sure you die in order to

• 7:31Matt Kirshen?

  for that

• 7:31Neil deGrasse Tyson?

  for us to evolve you.

• 7:33Matt Kirshen?

  That kind of that makes perfect sense. Yeah, again, that that's sort of a little mind blowing. Yeah, of course.

• 7:38Neil deGrasse Tyson?

  I'm not saying it doesn't make sense. I'm just saying I never heard anybody admit that.

• 7:41Matt Kirshen?

  Yeah.

• 7:42Neil deGrasse Tyson?

  So you're the first biologist I've heard be honest about the fact that Darwinian evolution requires that everybody dies.

• 7:53Speaker 02

  Yeah. So I mean, on the population at level level, at least when we think about synthetic cells, we really think about very, very minimal and living entities that are much simpler than the simplest cell that we currently know on earth. So much simpler. We are really talking something where essentially we we want to get to the point where chemical evolution becomes biological evolution, right? That's where we want to get. And in that context, I'm saying that if we manage to construct a system which is capable of self replication, then eventually resources will be exploited, especially if you have, if you have, of course, limited resources, right?

• 8:37Speaker 02

  And then this stage, this is where, you know, we have a situation where survival of the fittest is what's driving evolution, essentially.

• 8:45Neil deGrasse Tyson?

  We have a situation on our hands. So so this this conversion from complex chemistry to simple biology, that hearkens back to the Miller-Urey experiment, very famous experiment. When was that? In the 1960s, was it?

• 9:05Neil deGrasse Tyson?

  Perhaps early 70s. Could you remind us about the Miller and Yuri experiment? And what that did in your field back then?

• 9:11Speaker 02

  Yeah, so I think it was earlier even than that. It was around nineteen fifty, nineteen fifty-two or so. Where, yeah, so, um, so it was the first time, um, that essentially, uh, Miller was, was, uh, was performing chemical reactions in a way that is, uh, kind of similar to the, to early Earth, to the, to the environment on early Earth. So he was trying to recreate the atmosphere that was present on early Earth. And then, um, he could see that very simple building blocks of life, such as some amino acids, which build proteins, so to say, um, were present in that solution after he, after he, uh,

• 9:51Speaker 02

  provided the system with energy. Um, so that kind of shows that organic synthesis is possible under prebiotic conditions, essentially. Um, and, you know, that's far away from, from a biological system. So we're talking really individual amino acids, but it shows that prebiotic conditions can give rise to organic molecules like amino acids that build proteins today.

• 10:15Neil deGrasse Tyson?

  So in the Miller-Urey experiment, they knew to start with organic molecules, right? They knew to start with that, and they went to then see what the organic molecules might do for themselves.

• 10:30Matt Kirshen?

  Uh huh.

• 10:30Neil deGrasse Tyson?

  Let, when left unmonitored and left alone, but they had to give it an energy source, right? And if memory serves, that energy source was a little spark, very Frankenstein-like.

• 10:43Speaker 02

  Simulating lightning, so to say, on earlier Earth. Yeah.

• 10:47Neil deGrasse Tyson?

  You want a big night switch or something?

• 10:49Matt Kirshen?

  Yeah, I want a massive, I want a massive lever that someone, that a henchman, do you have a henchman? Do you, I, I'm hoping you have a henchman.

• 10:55Neil deGrasse Tyson?

  A henchman would laugh.

• 10:58Speaker 02

  I'm afraid not. But what I, what I find interesting about, about this experiment is that, you know, even before that, about hundred years earlier, um, there was the common belief among chemists at the time was that organic molecules are molecules which can only be synthesized by living things, right? Like, uh, that organic synthesis in the laboratory is essentially impossible. And then... Chemists at the time, like 1800 something, managed to actually make the first organic molecules synthetically in the lab, and that was actually urea. And that proved that we as human beings can synthesize organic molecules which are otherwise made by living things from scratch, right? And I see synthetic biology or the bottom-up creation of synthetic life a little bit at

• 11:43Speaker 02

  a similar, at a similar point right now, where, you know, kind of a proof of principle is needed to show that we cannot only make organic molecules, like the ones that were, that were made in the Miller-Urey experiment, but that we can also actually achieve a transition from matter to life in a laboratory setting.

• 12:02Neil deGrasse Tyson?

  How does your work follow this? And what is, what's different about your approach?

• 12:07Speaker 02

  So essentially, we start at a much, much later point. So we start when, we start with biomolecules, and we ask ourselves the question whether it's possible to actually assemble molecules in such a way that we can create a system that's capable of undergoing, that it created a self-sustaining chemical system that's capable of, of evolution. So that's, that's, that's our starting point and goal. And what we do in order to get there is we are, we are making lipid vesicles, so kind of the envelope of a cell, and we are building, constructing our own molecular machinery, and we do so with RNA, RNA nanotechnology.

• 12:50Speaker 02

  And that may be a bit reminiscent of the RNA world hypothesis and the origins of life.

• 12:57Neil deGrasse Tyson?

  As I understand your work, or any work that anyone does, you are only as effective as the tools you use. And if we are trying to assemble molecules, you need something that can, are they tweezers? You need some tools that are small enough to take this molecule over here and attach it to that molecule over there. And it seems like this is the RNA nanotechnology that you're referring to. Your toolkit are not mechanical tools, they're biological and chemical tools.

• 13:41Neil deGrasse Tyson?

  Is that, is that a fair way to characterize what you're doing?

• 13:43Speaker 02

  Indeed, indeed. So we don't use tweezers on a nano scale, although they exist, right? That's actually amazing part of physics, they do exist. But what we do is we actually do something very similar to what a protein designer would do, right? Protein design won the Nobel Prize last year and we do something similar, or we're trying to do something similar with RNA. And that's a much less explored field indeed. So RNA origami is quite new, but what we are essentially trying to do is we are trying to assemble a synthetic gene from scratch, a piece of DNA, which encodes for an RNA that folds up during transcription.

• 14:24Speaker 02

  So while the DNA is read off, it folds up into a desired structure. So that could be something that resembles a cytoskeletal element, or it could be something that resembles a nanopore that assembles into the lipid membrane of a cell so we can feed it, for instance. So the functionalities, so the forms are really driven by the function that we would like to create. And design happens with computational tools, essentially.

• 14:49Neil deGrasse Tyson?

  All right, so the folding, I'm fascinated by the folding.

• 14:52Speaker 02

  Absolutely, me too.

• 14:53Neil deGrasse Tyson?

  As a kid, I was into origami and I still am a little bit. I have big pudgy fingers, but I'm very delicate with the, with my little birds and the... I can still do it.

• 15:03Speaker 02

  Okay.

• 15:03Neil deGrasse Tyson?

  I got like three left in my repertoire that I can...

• 15:20Speaker 03

  I'm Nicholas Costella and I'm a proud supporter of StarTalk on Patreon. This is StarTalk with Neil deGrasse Tyson.

• 15:39Neil deGrasse Tyson?

  Do you know in advance how you need to fold your proteins? Because the protein itself is obviously not yet life. So you, you, do you know what you're doing? If, if, if you don't know, I mean, it's, it's rumored that this is what Einstein said. Research is what I'm doing when I don't know what I'm doing. Right? So if you're not targeting a life form you already know about, then how do you direct the decisions you make towards a life form that has never existed before?

• 16:14Speaker 02

  Well, essentially, we know what functions we need to realize, right? So we, we want, in the end, a self-replicating system which is capable to evolve. And in order to have that, first of all, this system is, needs to be able to build up its own molecular machinery and that machinery we build from RNA. And one piece that we think is crucial for such a machinery is actually kind of a machinery which can divide a lipid vesicle. So essentially impose a certain amount of membrane curvature on the membrane of a vesicle. And in natural cells, this happens via an architecture that's called the cytoskeleton, the skeleton of a cell. So one of the first kind of things that we build with RNA,

• 16:59Speaker 02

  that we build from RNA was actually cytoskeletal mimics, so to say, but all from RNA, not from protein. So we look at them, we look at how they look in nature, we look at how they function in nature, and we are trying to design something which looks very similar. So that could be, first of all, small building blocks that then assemble into micrometers long filaments that then can, for instance, attach to the membrane so that the membrane can be deformed. And because they are genetically encoded, we now have actually a quite powerful helper in that evolution. So essentially, we can then start to go to the DNA level, to the DNA level again, and introduce mutations so that we can evolve the RNA structures towards even better function.

• 17:47Neil deGrasse Tyson?

  Well, so you so you are introducing your own mutations.

• 17:51Speaker 02

  Well, we have biological machinery introduce them, essentially, yes.

• 17:55Neil deGrasse Tyson?

  You're not going to wait around a billion years or a million years, you're doing it yourself.

• 18:00Speaker 02

  We're doing two things here. We start with a rationally engineering starting point, right? So we already know what we want to get. So we have a very simple version that already works a bit. And then we let evolution brush it up, so to say.

• 18:15Neil deGrasse Tyson?

  Where does information theory fold into this? Because when we're taught DNA in school, we think of it less of a molecule, of course, that's what it is, but as something that encodes the biological information. And so how do you make sure that the information that's in there is the information you need?

• 18:39Speaker 02

  So that's where computational design really comes in, right? So we really start with, we think of what kind of 3D architecture do we want to create from RNA? And then we essentially design a synthetic gene, a synthetic piece of DNA, which upon transcription, so when it's read by the biological polymerase, will make an RNA that folds up on itself in desired way, essentially.

• 19:09Matt Kirshen?

  How much of the sort of design and the follow, you said it's done computationally. So how much of it is sort of designed computationally? And how much is it you physically do it and then you see what you end up with and adjust?

• 19:19Speaker 02

  First, we design computationally and then we physically do it. We check it in a lab with experimental techniques like cryo-electron microscopy to really visualize single molecules and their architecture. Then we can essentially see if the structure is entirely correct, if or if we need to make improvements on the DNA sequence level in order to fix certain things that we'd like to look ever so slightly different.

• 19:45Neil deGrasse Tyson?

  Is there a difference between you creating a life that we already know about? So synthetically creating a simple life? Because it seems to me that would be easier because you already have, you already know exactly what you're aiming for. Versus putting all this together and creating something no one has ever seen before. You'd still get a lot of credit in this world if you created a life form that already exists on Earth, just out of raw ingredients. That would still be amazing. But that's not good enough for you. You want something else to crawl out of the test tube.

• 20:22Speaker 02

  So essentially, there are different branches in the field of bottom-up synthetic biology, which use different types of molecules, different types of molecular building blocks. So either the very natural ones, so really taking pieces from cells essentially, proteins that you just encapsulate and boot, so to say, inside of a lipid vesicle. And then there is others who take entirely synthetic pieces. And then there is us, who is somewhere in the middle. And, you know, there is pros and cons to using the biological machinery. But in the end, you know, I could imagine that bottom-up synthetic biology brings about multiple examples of synthetic life, the ones that are very similar to life as we know it and ones that are quite far away.

• 21:06Speaker 02

  The problem with biology as we know it is that it's already extremely complex, right? So to give you an example here, right? All life on Earth that we know adheres to the central dogma of molecular biology, which states that DNA makes RNA, RNA makes proteins. And now this machinery alone requires, this step from RNA to protein requires 150 components, 150 genes, just for this step. So if we can circumvent the use of proteins and we just build a functional machinery from RNA, so we have our genotypes, our genotypes, so the DNA,

• 21:47Speaker 02

  but we have the function in the RNA, the phenotype is introduced by RNA, then we can reduce the complexity of the system quite a lot. And, you know, life has not always been that complex. At the origins of life, simpler solution must have been capable of sustaining self-replication and evolution. And therefore, I believe that building our own molecular building blocks, so to say, can actually be a shortcut. But we'll see, you know, all of these approaches are super cool. And in the end, it would be amazing to have not just biology 2.0, but also 3.0, 4.0, 5.0, and so on. So all of this is valid.

• 22:27Neil deGrasse Tyson?

  I like the fact that you took a look at life and said, "I can do a better job." And simplify it. It's very complex. Yeah, I can make, I can be, I can simplify that. That's delightfully audacious.

• 22:42Speaker 02

  Essentially, it's a bit, little bit similar to, to, you know, we came from the Miller-Urey experiment, right, where also you start with very, very simple building blocks. And I'm sure that the origins of life, self-replication and evolution have been sustained by a simpler set of building blocks. And, you know, one can ask if it's, if it's possible to, to, to use such, to use, well, to use such building blocks to, to, to start not from where life is right now, because that took four billion years to get there, right? But to start actually at a, at a simpler stage, essentially, but still have a system capable of evolution. That's really, that's really the holy grail, I would say here, because, you know, it's

• 23:25Speaker 02

  A, part of the fundamental definition of life, and B, will help us to, to get somewhere interesting.

• 23:32Matt Kirshen?

  So do you think life on another planet is likely to have something very similar to our DNA RNA protein system? Or do you think it could be a completely different self-replicating thing? Like, is it, is it likely that-

• 23:47Neil deGrasse Tyson?

  That's the million dollar question, because if we're looking for carbon-based, DNA-based life, on other planets, we might miss it. So another, another way to word this, I think, is how inevitable in the biochemistry of an early planet is what happened here on this planet with DNA to RNA to folded proteins? Is that so inevitable that you're saying, yeah, any place we find life, it would have been through this-

• 24:19Matt Kirshen?

  It would arrive at the same solution.

• 24:21Neil deGrasse Tyson?

  Would have found the same solution. Are you, are you prepared to say that?

• 24:25Speaker 02

  In other words, even like if we replay, if we replay history on this planet, right, would we end up with essentially the same thing? Or could we end up with something quite different? I said, the evolutionary landscape is vast, right? We're just with life as we know it, exploring a tiny, tiny, tiny, tiny, tiny bit of that. And I believe that- The idea of creating very minimal living systems from scratch will ultimately be able to help us to to address these kinds of kinds of questions, right? So you could, for instance, introduce metabolic pathways that are completely different from the ones that we know from life as we know it into such artificial systems and study them.

• 25:10Speaker 02

  So at the moment, we don't have evidence for silicon-based life, right? But I think there's, personally, I think there's also reasons for that, right? Like, both of them can do, can can make four bonds, right? But but but it seems that carbon is just much more versatile. And but, you know.

• 25:28Neil deGrasse Tyson?

  Yeah, carbon in the universe is also like five times more abundant. So silicon sits right under carbon on the periodic table. So just as she said, they can each bond four ways. Everything in that column can, so carbon has four four electrons in its outer shell, and it can take four more, right? Which is a highly versatile situation to be in. And but silicon can do that, too. But we don't need, I I I'd be fun to find silicon-based life. We just don't need it because carbon is everywhere in the universe.

• 26:06Matt Kirshen?

  Does the same job, but kind of better.

• 26:07Neil deGrasse Tyson?

  But yeah, so so do do astrobiologists call you and get your insights into what they might be looking for?

• 26:15Speaker 02

  I would say the field is very, very interdisciplinary. Bottom up synthetic biology is very interdisciplinary. And we're for sure, we're for sure keeping the discussion entirely open and with astrobiologists and really also think about, you know, implementing well, solutions that evolution may not have explored, right? And so that's for sure a super interesting conversation to be had.

• 26:42Neil deGrasse Tyson?

  You know something evolution did not come up with? A four-legged vertebrate creature that also has wings.

• 26:51Neil deGrasse Tyson?

  But we've we've we have Pegasus. Pegasus popped some wings out his back.

• 26:55Matt Kirshen?

  Right.

• 26:56Neil deGrasse Tyson?

  That that is not in the plan. Okay, so when you look at life on Earth, do you say here's something that evolution could have should have maybe but didn't?

• 27:10Matt Kirshen?

  But it does it again, from my limited knowledge, it does seem that evolution does seem to keep landing on the same solutions for,

• 27:17Neil deGrasse Tyson?

  Oh, interesting.

• 27:18Matt Kirshen?

  There are a bunch of different animals that have evolved through different pathways, the same things.

• 27:22Neil deGrasse Tyson?

  Yeah, yeah, Carson, is that that I like what he said there.

• 27:25Matt Kirshen?

  Is that the same at the lower level?

• 27:27Neil deGrasse Tyson?

  Yeah, evolution has found similar pathways to solve its survival problems that in some are even unrelated, but they land in the same place. So that might give you insight, does it to for what biochemistry likes?

• 27:43Speaker 02

  Yeah, and and I think one place where we could see this, for instance, is that when we build our life, our our very, very minimal synthetic cell as the minimal unit of life. And I don't mean really a cell as we know it, but a very, very simple version of that essentially, that that cell is by far not as efficient as life as we know it, because it's based its catalytic activity is based on RNA and RNA catalysis is much slower than what proteins can do. And the moment you introduce proteins to the system, so a way of having translation of of of of making,

• 28:25Speaker 02

  producing proteins inside of a synthetic cell, you may find that this is actually a much more efficient solution. So this may be why we don't see an RNA world around us anymore, simply because, you know, once you have proteins, they win in a direct competition. But again, if we start with a simple system, evolution may bring about these more complex systems, right? So in fact, in fact, if you look at the ribosome, so the ribosome is the component in the cell, which is responsible for turning RNA into protein. So it's doing this translation inside of the cell. Then that ribosome, the catalytic activity, the core of the catalytic activity actually comes from RNA and not protein.

• 29:08Speaker 02

  So indeed, we have molecular, some of the most intricate molecular machines that cells use today are actually RNA based.

• 29:16Neil deGrasse Tyson?

  We want, when the aliens come, we want you in the room when that happens. So that you might be able to understand what kind of life they are, right? You'd be perfectly suited for this. Is that correct?

• 29:27Speaker 02

  Well, let's see what they look like, right? I may or may not.

• 29:31Neil deGrasse Tyson?

  As I understand it, correct me if I'm wrong. All life on Earth has a certain handedness in its molecules. Like it's all left-handed or it's all right, whatever it is. Because some molecules are, they're, they're not symmetric.

• 29:50Neil deGrasse Tyson?

  Like they're mirror versions of them.

• 29:52Matt Kirshen?

  Right.

• 29:53Neil deGrasse Tyson?

  And so we're all one kind of molecule. Which one is it? Left or right-handed? I forgot which it is.

• 30:00Speaker 02

  Left-handed. Yeah. So that origins of homocherenity, actually. Um, so the handedness of life, so to say, is another very, very interesting question. So in fact, we talked about the Miller-Urey experiment, right? Where amino acids were produced. And actually, in that experiment, a resemic mixture of these, of these molecules was produced. So the left-handed version as well as the right-handed version, right? So that experiment does not solve the origins of homocherenity at all. And that's another very, very interesting field of study, I have to say. Um, of course, the molecules that we use are all the standard handedness, you know, that life uses today.

• 30:39Matt Kirshen?

  This might be a dumb question, but of the left-handed and right-handedness of the molecules, which one's good and which one's evil?

• 30:48Speaker 02

  Well, I'd say which one has nature chosen and that's the left-handed one, yeah.

• 30:52Neil deGrasse Tyson?

  That's a separate lab they're working on.

• 30:54Matt Kirshen?

  Okay, okay.

• 30:56Neil deGrasse Tyson?

  Since biochemically, there's no difference between making life forms with left or right-handed molecules. In principle, both handedness could have started on Earth.

• 31:12Neil deGrasse Tyson?

  Is there a search for right-handed colonies of life on Earth that are thriving in their own little world and no one knows about them? And somehow the left-handers took over the world, suppressing any uprising of the right-handed molecules?

• 31:29Matt Kirshen?

  I don't like that kind. I don't like those righties.

• 31:32Neil deGrasse Tyson?

  We do it for less.

• 31:33Matt Kirshen?

  Yeah.

• 31:34Neil deGrasse Tyson?

  As humans, don't we?

• 31:59Neil deGrasse Tyson?

  Is any thought as to whether, if we look harder, we might find a right-handed colony of life?

• 32:05Speaker 02

  I believe we should see traces of such forms of life if they were existent. So the fact that we don't see those traces, the fact that we don't find any, you know, wherever we take probes on Earth, we don't find any of these molecules, make me believe very strongly, and I don't know, it's not my field, but make me believe very strongly that, you know, the left-handed version is the one that made it.

• 32:31Neil deGrasse Tyson?

  It's the good that has triumphed over the evil. She didn't say that, but that's what she meant.

• 32:36Matt Kirshen?

  Well, we don't know. We don't know. All the evil that triumphed over the good. There's no way to...

• 32:40Neil deGrasse Tyson?

  Oh, yeah. If you only have one, you don't know whether you're the evil one or the good one.

• 32:44Matt Kirshen?

  Which one has the moustache? The moustache...

• 32:46Speaker 02

  You can, of course, make mirror versions of molecules in the lab. So that is possible. And that sometimes can even be desirable, for instance, for therapeutic applications because their degradation and recognition properties and so on are different, right? Because our machinery in the cells, well, does not really, does only recognize its own kind, so to say. So in that sense, yeah, it's interesting to think about it.

• 33:10Neil deGrasse Tyson?

  So Kirsten, just like in the Miller-Urey experiment, they tried to create what they thought were the conditions in the early Earth. You, in your biochemical experiments, presumably the environment has some temperature, some air mixture of molecules. Presumably, you're doing the same thing, but in a more advanced way. We now have a catalog of nearly 6,000 exoplanets, and we know some things about them. Are these conditions that can inform your experiments as we look for life on other planets? And are the conditions you do your experiments in, how realistic

• 33:51Neil deGrasse Tyson?

  are they? Because we have life on Earth that is living in the ice and living on the sides of volcanoes and all the extremophiles. So are you testing for conditions that would, an extremophile would be happy in, rather than just us?

• 34:09Speaker 02

  So typically, we test conditions that are compatible with our research budgets. And this typically means that we take conditions which are as simple as possible, right?

• 34:20Matt Kirshen?

  So you're not in a volcano right now?

• 34:22Speaker 02

  Yeah, exactly. Like, if you want to work in an atmosphere that's not, you know, what is around us, experiments all of a sudden become much more complex and costly and difficult, right? So in our case, when we, you know, what we want to do is to create a version of synthetic life. And we don't really care, we want to make our lives as easy as possible because the question itself is hard enough, right? So we typically try and work at either room temperature or 37 degrees, which all laboratory equipment is designed to be compatible with. And we work with DNA and RNA. We produce synthetic genes in standard manners that biology

• 35:07Speaker 02

  has come about. And so we take the conditions as they are. Of course, these days, you find sophisticated experiments and sophisticated pieces of equipment, which are at least partially trying to replicate these more extreme conditions, where we could talk, you know, astrophysics and alien life, or conditions that resemble more the origins of life on early Earths. In our case, we're just taking what works, the simplest systems.

• 35:35Neil deGrasse Tyson?

  37 degrees Celsius.

• 35:37Speaker 02

  Oh, I'm sorry, yes.

• 35:42Neil deGrasse Tyson?

  You're speaking to us from Europe. We're here in America. Let's talk about something that I know is on everyone's mind. What are the ethics of this exercise? Might you create something that will crawl out of the beaker? Or out of the test tube? And then?

• 36:03Neil deGrasse Tyson?

  Become our overlord? Or infect us all? And we all die?

• 36:08Matt Kirshen?

  And would it see you as its natural parent?

• 36:11Neil deGrasse Tyson?

  Or as its creator?

• 36:13Matt Kirshen?

  Creator, yeah.

• 36:15Neil deGrasse Tyson?

  She is their god, right?

• 36:17Matt Kirshen?

  Their god, but then also they hit the rebellious teenage phase and they're like, I don't even want to be alive.

• 36:23Speaker 02

  I don't think, I don't think anything we create will crawl out of the test tube anytime soon, right? So we are after a very, very minimal version of a synthetic cell, which is much less complex than than life as we know it, right? So essentially, you know, life as it evolves came with robustness. What we are creating is very, very fragile and requires a lot of care, so to say. And but you're completely right, like ethics to consider ethics is of course extremely important. So, you know, one may think about things like, okay, once you have a self replicating system, should the same rules apply as for life as we know it in terms of bio containment?

• 37:07Speaker 02

  For instance, so we have very good containment rules for for organisms, especially for engineered organisms. We have to work at certain biosafety levels depending on their risk for the environment and the human being. And so to use these kinds of rules also for or to extend these kinds of rules also for synthetic life. And to understand the risks as well as the opportunities is is is super important, of course.

• 37:36Neil deGrasse Tyson?

  Let me ask the most basic question of them all.

• 37:41Neil deGrasse Tyson?

  Why are you doing this?

• 37:45Matt Kirshen?

  It's a question I ask myself every day.

• 37:48Neil deGrasse Tyson?

  Did you wake up one morning? Now you're going to be responding for everyone in your field with this question. Did you wake up one morning and say, you know, I'm not happy with the biodiversity of life on Earth. I want it even more diverse. And then you say, I want to invent life. Because that's a different goal. I'm just trying to understand how life formed on Earth. How we went from organic molecules to self replicating life. That, that has a certain accessible. Yeah, I understand. That's a frontier of biology. But now you want to create something. So where's the ethical line between trying to

• 38:31Neil deGrasse Tyson?

  understand how life started and trying to create life?

• 38:36Speaker 02

  Yeah, look, we have extremely limited knowledge about the exact conditions on early Earth, right? And there's only so much we can know about this. So experiments in the end need to be reproducible. We have only one example of life as we know it. And I'm just super, super curious, you know, about what life is and what it could be, right? So all those questions that your parents can't answer when you were a kid, right? So I think it's, I think it's somehow intrinsic to human curiosity to, to ask what life is and why it's there and so on. And recreating it, building it is one way to really bring our understanding of life to a new level, I believe. But from a practical point of

• 39:18Speaker 02

  view, right, where you could, you could think about evolving such very minimal entities, with such very minimal entities towards user defined goals. So this could be in immunology, this could be a new way of making evolvable materials. So this could really be a new way of manufacturing, manufacturing in the end. So while, you know, we come in with curiosity, we are, synthetic cells and synthetic life have really the potential to revolutionize, to revolutionize the way we manufacture on Earth, right? I mean, just, just look around you, right? I mean, if you, it's amazing to see the generative power of evolution, right? Like, nature has built.

• 40:01Speaker 02

  Ginormous architectures that capture CO2. I mean, look at trees. Nature has built cells which capture pathogens inside our body, right? So, and all of this just comes from the same common ancestors. So imagine we could create synthetic life and evolve it really towards user-defined goals. And I think, yeah, I think, I think this is, in the end, what motivates us is a very fundamental question and the creation of tools and evolvable systems that can be evolved in the end. And I think RNA design is a really nice example, where, we talked about it earlier, where, where both of it comes together, right? I mean, we all know about RNA therapeutics.

• 40:45Speaker 02

  There's a thirty billion dollar market right now. And so advancing RNA design has immediate implications also on the, on the therapeutic level. And at the same time, it allows us to answer some of the, or to address, to, to deal with some of the very fundamental questions. So I feel like it's a super nice sweet spot to study RNA and lipids and their interactions and so on.

• 41:06Neil deGrasse Tyson?

  Yeah, I, I'm embarrassed. I didn't think of any of that when I asked you that question.

• 41:11Neil deGrasse Tyson?

  So, I, I should have, of course, now that you mention it. It's so clear and present that there, there are things that your work can do that can improve the state of human health in the world and our relationship to other animals or, or the biome that we're immersed in, in our gut, on our skin, just, you could, you could be the, the savior of us all.

• 41:38Speaker 02

  Well, it's clear, for instance, right? We talked about RNA, RNA folds and RNA design. So, RNA, like mRNA, as it is in our vaccines, is inherently unstable, right? That's what makes the deployment so difficult. You have to cool it down to, to, to preserve it. And now, when you fold RNA in distinct ways, you know, the RNA origami, the RNA nanostructures we make, they are stable at room temperature for days, just on the bench. And so, by folding RNA, we can also package more on a smaller footprint, right? Right? So, by making nanostructures from RNA, I really think we can advance the way we build therapeutics and at the same time, actually also address these very fundamental questions

• 42:21Speaker 02

  on, you know, origins of life and creating of, of very minimal synthetic cells and synthetic life.

• 42:27Neil deGrasse Tyson?

  I think we got to end it there, but this has been a brilliant conversation. Delighted to learn that such a field exists that is vibrant and that you're in the middle of it. That gives me confidence that only good will come of this. Again, thank you for your time and like I said, delighted to know that this is a field that's vibrant and probably still growing. And I look forward to see what it will deliver to civilization. For sure. Yes. All right. Thank you for being on StarTalk. Thank you. Matt, thanks for coming through.

• 43:01Matt Kirshen?

  This was fascinating. Thank you for having me.

• 43:03Neil deGrasse Tyson?

  And I keep forgetting you're in, you're in LA.

• 43:05Matt Kirshen?

  I'm in LA.

• 43:06Neil deGrasse Tyson?

  And I got a book coming out in a few months.

• 43:09Matt Kirshen?

  Yeah, we're going to steal you for probably science if we can.

• 43:11Neil deGrasse Tyson?

  I'd be happy to go on might be science. Sorry, what's it called?

• 43:15Matt Kirshen?

  We think it's science. Probably science is my podcast.

• 43:19Neil deGrasse Tyson?

  What comes out of my mouth will be science. Change the name of the show for that episode.

• 43:23Matt Kirshen?

  When you're on, we change the name. Otherwise, probably when it's us and other comedians who know very little.

• 43:29Neil deGrasse Tyson?

  All right. So that's all we've got here on StarTalk. Neil deGrasse Tyson, as always, bidding you to keep looking up.