Could Blind Forces Build a Self-Replicating Molecule?  

Episode 1747 May 10, 2023 00:34:27
Could Blind Forces Build a Self-Replicating Molecule?  
Intelligent Design the Future
Could Blind Forces Build a Self-Replicating Molecule?  

May 10 2023 | 00:34:27

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Show Notes

On today’s ID the Future, scientist and Stairway to Life co-author Rob Stadler and host Eric Anderson examine a recent PNAS paper on origin of life, “An RNA Polymerase Ribozyme that Synthesizes Its Own Ancestor.” A superficial look at the paper—and the paper’s title in particular—might give the impression that the laboratory findings behind the paper render the blind evolution of the first self-replicating biological system appreciably more plausible. Not so fast, says Stadler. Listen in as he and Anderson highlight various ways the laboratory work in question is wildly unrealistic. And for a video exploring the many problems involved in blindly evolving the first self-replicator, check out a new Long Story Short animated YouTube video, created with input from Read More ›
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Episode Transcript

Speaker 1 00:00:05 ID the future, a podcast about evolution and intelligent design. Speaker 2 00:00:12 For decades, the Holy Grail for Origin of Life researchers has been creating a self replicating molecule, some kind of polymer that can make copies of itself with the idea that once that is achieved, then Darwinian evolution can step in and take over to build the first living organism. But just how close are we? Welcome to ID the future. I'm Eric Anderson, and on today's show, we're joined again by one of our regular guests, Dr. Robert Staler, to talk about the origin of life and this effort to build a self replicating molecule. Staler received a degree in biomedical engineering from Case Western Reserve University, a master's in electrical engineering from M I t and a PhD in medical engineering from the Harvard m MIT Division of Health Sciences and Technology. He has worked in the medical device industry for more than 20 years, has over 140 patents, and his co-author of the book, the Stairway to Life, an Origin of Life Reality Check. Great to have you back on the show, Rob. Speaker 3 00:01:04 Hey, thanks Eric. It's a pleasure to be here. Well, Speaker 2 00:01:06 Rob you sound great. I know you're joining us today all the way from Crackow Poland, so I appreciate you, uh, being on the show today. Te tell us what you're doing there. Yeah, Speaker 3 00:01:14 Well, in my, in my day job, I'm, I'm a scientist and, um, I'm here doing a clinical study and we're trying to find out the best locations to pace the heart of the patient that has heart failure and asynchronous contraction pattern to try to get it back to being synchronous and get them out of heart failure. That's the study. Speaker 2 00:01:34 Fantastic. Well, sounds like you're doing some great work that is really having an impact on people's lives, so appreciate you taking time to join us today. Speaker 3 00:01:43 My pleasure. Speaker 2 00:01:44 So, Rob, just, uh, sort of step back for a second, sort of the 10,000 foot big picture idea. So this concept of self replication is really fundamental for origin of life researchers. Why is that? Speaker 3 00:01:55 Yeah, well, everybody knows that if you're gonna have life, it has to replicate, but replicating an entire cell is way too complicated to try to get that started prebio. And so it's envisioned then, as you kind of said, that getting a molecule, an information containing molecule that can self-replicate would be the first and the most simple and rudimentary start of replication. And as you said, this naturalistic origin of life or a biogenesis is a complete non-starter if you can't show that this is possible. Mm-hmm. Speaker 2 00:02:33 <affirmative>. Yeah, and I think it's important, again, just to emphasize for our listeners, a lot of people are under the impression that origin of life is, you know, one field and Darwinian evolution is something totally separate, but it's very clear from the main origin of life researchers, whether we're talking about show stack or Joyce or others, that they are absolutely counting on Darwinian evolution to do all the heavy lifting and to build the first organism. And so their hope is if we can just get a self replicated molecule, then Derbin evolution can step in and take over. And so that's why there's so much emphasis and so much focus on this idea of a simple self replicator, if you wanna say it that way. Speaker 3 00:03:10 Exactly. The stakes are high and they know that they're <laugh>, their beliefs are on the line, so they really have to prove this. There's gotta be evidence somehow. Speaker 2 00:03:20 Well, I mean, look, Rob, if you start from the assumption that there must be a naturalistic origin of life, it just had to have occurred, then you're kind of in a position where you have to say that something like this happened, aren't you? Speaker 3 00:03:33 Yeah. And the evidence must support what you believe. Speaker 2 00:03:36 Yeah. Yeah. So, Rob, you've been heavily involved in the wonderful long story short videos on YouTube along with several other PhD scientists, and the most recent video that came out a few weeks ago, I think is the eighth in the series. It's about this idea of self replication and some of the challenges to getting a bonafide self replicating system. Tell us just a little bit about a couple of the things that your team discussed in that video. Speaker 3 00:03:58 Yeah, well, the video spend some time actually reviewing a paper by Jack who raised several concerns over the concept of self replication. And we appreciate him being candid in, in showing some of those concerns. And it goes through some of those, some of those I think we'll go through in detail here as we get in deeper. Speaker 2 00:04:18 Yeah. And, and of course, shows stack is one of the leaders in the origin of life area. And so it's great that he pointed out these are the, I forget it was like a half a dozen things that were issues with getting a self replicated system. Of course, the thought is, Hey, don't worry. We'll, we'll get over these <laugh>, you know, at the end of the day this will be, this will be solvable. But it was nice that he at least outlined those. Speaker 3 00:04:38 And it's quite surprising to me how often I see in media that all claim that this has already been accomplished. It's dones not so surprising that people are told to believe that because these scientific manuscripts themselves have such provocative and, and convincing sounding titles. And I think it started with Saul Bigelman back in 1967 when he wrote a paper called an Extracellular Darwinian Experiment with a self duplicating nucleic acid molecule. And then you'll see, you know, Gerald Joyce wrote a paper called Self-Sustained Replication of an RNA Enzyme, uh, another review paper with with jacks called Proto Cells and RNA Self Replication. Yeah. And then the paper we're gonna dive into today is called an RNA polymerase that ribosome that synthesizes its own ancestor. Right, Speaker 2 00:05:36 Right. Yeah. There was another famous one that, that they did called the Self replicating Ligase Ribosome, I think is, I'm just going off the top of my head. But yeah, so that, that concept of self replication is not just put forward as, Hey, something that we're working on. If you read the titles of these papers, you'd think it's, it's done <laugh>, you know, we've got lots of these out there, there's different ones and they're all working. Yep, Speaker 3 00:05:57 Yep. Lots of optimism. Speaker 2 00:05:59 Yeah, exactly. So let's go ahead and dive into this new paper, which is really focused on a self replicating molecule, specifically a self replicating r n a molecule. So again, the title of this paper just for everybody, this mouthful here, it says an R n a polymerases Rib Ray's rib that synthesizes its own ancestor. And this is, uh, from Joyce and his team and was edited by Jack Shostak. So this is just not some paper that's out there. These are some of the most well known origin of life researchers. So Rob, give us a little bit of background about this paper. What are they focusing on? Speaker 3 00:06:32 Yeah, so they, they have been working for years with artificial selection and not natural selection, but artificial selection of different RNA molecules to try to find one that is the most successful in, in taking a template of RNA and building a copy of it. Speaker 2 00:06:52 Yeah. And by years, let's make sure people understand decades. Speaker 3 00:06:55 Yeah. It's, it's been a long time coming and so it's rather a complex RNA now that they have artificially selected and you could say evolved through human help <laugh> mm-hmm. <affirmative>, but they're sort of showcasing the, the functionality of this, the latest and greatest. Speaker 2 00:07:13 Okay. And so, just to kind of back up a little bit, I know that years ago there had been a simpler system, I think it was Joyce had worked on with his colleagues where they had, and this is the paper that I mentioned, a self replicating lyase rib design, where they essentially had an RNA that was able to catalyze a single, uh, reaction to join two strands together. Tell us just briefly about that experiment and then how this one differs. Speaker 3 00:07:38 Yeah. That one is highlighted in that long story short video, and the analogy there is if you had a car that you cut in half and then you had another car come along and it pushed the two halves together so that they joined and formed a, a functioning car, and then you claimed that you had now created the world's first self replicating car <laugh>. That, that's basically what that paper is doing because it's a, it's a, it's a rib r n a a strand of RNA that's able to create a single bond between two halves of itself to bring those together to create a full version of itself. And they claim that was self replicating. Speaker 2 00:08:19 Yeah. I, I love that example from the video because it's really helpful for, you know, you deal with molecules probably at some level, but most of us don't on a day-to-day basis. So it's really helpful for us to see that example of the two halves of the car coming together, uh, because what they did was, yeah, they have this, this, uh, r n a, which is able to catalyze a reaction, and then they split it at the point where those particular, uh, nucleotides join. And so then you go out and buy and I mean, literally buy from the polymer store, the two strands, and then you have the one that bly GCEs or puts together those two nucleotides and boom, you've got a second one and you claim self replication. So it's, it's really, uh, it's really an interesting thing that can get lost in the details. Yes. Uh, for most of us who aren't familiar with how the molecular system is working at the nucleotide level. So it's great to see that car example that you guys did in the video. Speaker 3 00:09:12 And a really important limitation too is that in that experiment, there's nothing hereditary being passed along. Mm. Meaning that the, the molecule that's doing the bonding, the ribo is not passing its information along to the combination of those two parts. All it's doing is bonding them together, and then they go off and do their thing. Speaker 2 00:09:35 Right. Yeah. And that reaction is just gonna continue within that, within that test tube, if you will, until it runs out of reagents and then it's done. Exactly. There's no control over it really or anything. So. Interesting. Okay. So there's been a lot of work over the last 20 years since that paper. So what's this new paper? How does it differ in terms of what they're trying to do? Speaker 3 00:09:55 Well, what's different here is that they're actually coming up with a ribo that is, is doing more of the nuts and bolts. It's actually taking, uh, individual nucleotides and matching them up to a template mm-hmm. <affirmative>, so they're complimentary to the nucleotides already strung together in the template, and it matches them up one by one attempting to replicate the template. Speaker 2 00:10:20 Okay. So that's a significant change, right. Because previously they had gone to the polymer store and bought the two halves. Uh, now, now they're actually taking a polymerase, which is taking individual nucleotides and joining them together, which is more like what we see in, in real living systems. Right. So that's an important change here. Speaker 3 00:10:39 Yep. But there's still a whole lot of, um, whole lot of cheating going on. I can, that's a strong <laugh>. Speaker 2 00:10:45 Yeah. All right. Yeah. May maybe, uh, let's, let's jump in. Let's talk about a few of these things. So, so as this polymerase, um, comes along and a polymerase just, just for everybody who, who's listening, uh, who may not be familiar, this is basically a protein or a molecular machine, you can think of it that takes two nucleotides and joins them together to make more nucleotides. Right. And make, make a longer polymer. We call it a string of nucleotides. So that's the polymerase. So this polymerase is making three strands. Right. And then those strands can supposedly spontaneously self-assemble to form a copy of that polymerase or a copy of an older type of polymerase. Speaker 3 00:11:26 Yeah. They're, they couldn't get it to do the polymerase itself, so they aimed at its ancestor, you know, a former version that was a bit simpler, but what what they started with is it's got 188 nucleotides, so you can think of a sequence of 188 letters mm-hmm. <affirmative> to make up this rib. And that's, that's quite complicated. I mean, to have something like that randomly form Yeah. I think you'd be more likely to find a single atom somewhere in the universe than to get a molecule like that that just came together on its own, quite complicate. But to get that thing to start to, to build other RNAs based on a template. So you wanted to sort of copy the template. You first have to start off with, with a really pure environment. Ok. And that's what they do in the laboratory. So that's kind of cheat number one is that what they put in the solution to get this to get started is just pure individual nucleotides. Mm-hmm. <affirmative>. Now maybe somebody can argue that a prebiotic earth or out there in space somewhere, there's the opportunity to form nucleotide, like in a meteor or comet or something. But getting those separated out from all the other organic junk <laugh> that that would form is extremely, I don't know how you would get that to happen in a prebiotic world. Speaker 2 00:12:49 So, so to put it bluntly, Rob, if you have molecules that are floating around and bumping into each other, they wanna react or nucleotides, right? Yep. And so if you just got these things in the premortal soup, to use that term, uh, interacting with each other, you've got some serious levels of additional interactions that could take place and come up to works. And so that's been avoided by the lab scenario is what you're saying? Speaker 3 00:13:13 Yep. Instead of millions of diverse compounds, and the vast majority have nothing to do with life. Mm-hmm. <affirmative>, what they presented in the test tube was just the compounds that they want. And, and I'm not only talking about just having pure nucleotides, but exactly only the proper chirality of those nucleotides. So each, each RNA nucleotide has, uh, 16 different chiro forms, and only the one is the one you want. And so in their test tube, they only had the right one, uh, each time, and that's the hard to come by. Another thing that's very specific is the, the magnesium ions that they put into the solution. You gotta have some magnesium in order to get this process to work, but if you have too much magnesium, it destroys the RNA that it's trying to produce. So all the conditions were just right to make this happen. Speaker 2 00:14:12 Okay. Yeah, no, that's, that's important to keep in mind anytime. So, so even if, let's back up a second. Even if someday somebody were to produce a self replicated molecule in the, um, in the lab, which I don't think is gonna happen, but anyway, let's suppose that were to take place, that would be a very different thing to say, all right, now we can take this out into a prebiotic environment on its own and ha still have it work. Speaker 3 00:14:34 Exactly. It's a hugely different environment and, you know, they're using the best conditions in the lab. Just try to get this, try to get this, uh, demonstrated and write a paper about it. That's the goal. Speaker 2 00:14:46 Sure, sure. Okay. Well, let's, let's let 'em go ahead and use their pristine conditions and the setup exactly the way they want to try to get this to at least, you know, as a proof of concept. What, what other kinds of things are going on here that, that might be a little bit erase some eyebrows, perhaps Speaker 3 00:15:02 <laugh>? Well, there are many. It turns out that if you just have individual nucleotides and you put them in water, you often see videos where these individual nucleotides just link up to the template, uh, comp complimentary. Yeah. They just complimentary link up in what's called Watson Crick base pairs. But the challenge there is that water actually forms better hydrogen bonding to these individual nucleotides, then they form to each other. And so you don't just get individual nucleotides to just pair up like you see, if you're in water, somehow you've gotta get the water outta the way, or you have to use like, at least four nucleotides bond together in what's called an A liga. And now you've got enough Watson Creek bonding to get those to come together and get the water outta the way. Speaker 2 00:15:52 Okay. That's very interesting. So there's a hydrolyzed, I guess is the right term where the water tends to break the bonds apart. Speaker 3 00:15:59 Well, the water just just interferes because it wants to hydrogen bond. Yeah. So it, it's like they already have a partner, they don't, they don't need a new partner. Speaker 2 00:16:08 Yeah. Yeah. Does, does the water tend to break apart an RNA polymer, or not necessarily? Speaker 3 00:16:13 It does. After you've got an RNA polymer sitting around, it'll, it'll fall apart. That, that's also something they ignore at these papers. It's natural degradation. Speaker 2 00:16:23 It's similar to the problem that you have with linking amino acids in water. Speaker 3 00:16:27 Yep. Speaker 2 00:16:28 So they just Speaker 3 00:16:29 Yep, yep. They naturally come apart and they don't naturally go together. Mm-hmm. Speaker 2 00:16:33 <affirmative> Speaker 3 00:16:33 Mm-hmm. <affirmative>. And then if you do get, uh, nucleotides to bond in life, all of RNA and DNA has a specific kind of bond between the nucleotide. It's called a three prime, five prime phosphodiester bond. And that's just a very regular way that they bond to each other to form a perfect sequence. But in a prebiotic situation like this, they can bond together in all kinds of different ways. So imagine you wanna get a bunch of humans to hold hands and make a chain of mm-hmm. <affirmative> humans. But once in a while, one of the humans grabs another person's foot instead of a hand. And so you kinda make a link, but it's a broken weird link. That's what often happens here. It's very difficult to get perfect bonding in a, in a long polymer. Speaker 2 00:17:20 Yeah. Interesting. Do you happen to know, I don't know if you know this right off the top of your head, but do you happen to know whether there's a particular preference for the correct link? Or is it kind of a random, Speaker 3 00:17:28 I believe the two prime, five prime and the three prime five primer about equally likely. Okay. There may be a slight preference for one or the other, but I know that, uh, in life you don't have any two prime five primes. Those are bad. Speaker 2 00:17:41 Mm-hmm. <affirmative>. Okay. Speaker 3 00:17:43 And then, you know, they're expecting these rib designs to do the work and to work on a template, which would be, you know, trying to copy themselves. But one big challenge with this is that in order for RNA to be functional, it has to be folded up into a mm-hmm. <affirmative>, basically a three dimensional structure, and that's how it's catalytic ability comes about. But in order to be copied, it has to be unfolded. You need it kind of like a nice straight line of sequence of monomers there so that you can, you can line up things and make a copy of it. Yeah. So at the same time, you need to be folded tightly and unfolded, which is a contradiction right there. Speaker 2 00:18:26 Yeah. You've got two things working across purposes, which is important and, and just, I, I think most listeners will know, but just the ribo term is just a fancy way to say an RNA polymer that can perform a catalytic function. Exactly. Speaker 3 00:18:39 So, Speaker 2 00:18:40 So, yeah. So we've got this, you a need to have the RNA laid out in a nice straight strand, which probably isn't gonna happen on its own in water anyway, for the most part in order to be copied, but then it's gotta be folded properly in order to performance function. So that's a nice juxtaposition of those two things that are working at cross purposes in some ways. Speaker 3 00:19:00 Yep. And then once you get the monomers lined up on the template, right. So you're making a complimentary copy of that template. Once you get to about 20 or 30 nucleotides in length that are, that are matched up to the template, you get such a strong bonding between those two strings are 20 or 30 in length, that it turns out that not even boiling water can get those to separate. Speaker 2 00:19:27 I Interesting. Speaker 3 00:19:27 They're stuck together. And so if you use very high temperature water, you're gonna end up actually destroying the molecules before you get them to separate. Hmm. Speaker 2 00:19:37 Okay. So assume we can get a, a rib to take some monomers, take some single nucleotides to line them up in a strand, and we could somehow find a way to get that strand separated properly. In the paper, they were talking about building three different strands that are pieces of a, I think they called it an ancestor polymerase. Tell us about that. Speaker 3 00:20:01 Yeah. So the, the rib itself was 188 nucleotides in length mm-hmm. <affirmative>. And that was too big and too complex to try to replicate. So they decided they could, they could break it into three parts and try to have this, this rib replicate each of those three parts. Speaker 2 00:20:20 Ok. Speaker 3 00:20:20 Now, when they did that, often the ribba would produce something that's too short, you know, it, it didn't finish its job. I, and I should back up and say they, they first had to give for free, they had to offer up a, a primer, what they call a primer, which is like a short string, maybe it's 20 nucleotides that is already a match to the template. It's, it's sort of a freebie or, or a, a headstart mm-hmm. <affirmative> that's provided and that, that gives the rib a headstart <laugh> or else it couldn't get started on its own without this primer. So that's another kind of cheat is where do you get that primer that nicely matches the beginning of the template you're trying to copy? Speaker 2 00:21:03 Well, in 20 nucleotides is not insignificant. I mean, if you're expecting that to form on its own by random and just show up, that's <laugh> not gonna happen. Speaker 3 00:21:12 <laugh>. Yeah. And if you expect this life to get started in a proto cell that has a membrane to it on a liga of 20, you know, nucleotides, that's, that you call a primer, it's not gonna be able to just diffuse through that membrane and show up ready for work. Where, where are you gonna get that? How's it gonna get into that proto cell? Speaker 2 00:21:32 Mm-hmm. <affirmative>. Mm-hmm. <affirmative>. Yeah. I was just finding here in the paper it says, thus we attached external primer sites added to both ends of each fragment. And uh, yeah, you're right, it did, does mention 20 nucleotides long. So that's a pretty big deal. You're, you're adding a primer at both ends. You've got 20 nucleotide primers, and somehow those just show up. Okay. So, so go from there. Speaker 3 00:21:53 So after they <laugh>, after all those layers of, um, helping the situation out, I would say then they found that the yield for this rib to produce those three parts, even with all the help, the yield was about 1% for each, each of those three components. And I don't know of any manufacturing process that, that could possibly survive. Speaker 2 00:22:17 You'd run outta business pretty quickly, had a 1% yield. Speaker 3 00:22:21 Yeah. Cause it's not just that, you know, 99 are junk and one is good, but you need to find three good ones to come together to make the final product. And you're randomly piecing together some bad, some good, some bad, some good. And Speaker 2 00:22:37 Yeah, I was just gonna say, back to the problem we discussed earlier, if you've got 99 bad ones floating around in the medium Speaker 3 00:22:43 Yeah. And it's, it's actually kinda multiplicative. If you have 1% yield for part number one and 1% yield for part number two, 1% yield for part number three, and you need all three good parts to come together, you're actually at a, like a one out of a million chance now that you're gonna get all three parts to come together. Speaker 2 00:23:02 Okay. All right. Well, let's, let's carry on from there, Rob <laugh>, let's assume that we, we got our one out of a million and we've got three strands that are coming together. And again, these are not strands that conform this polymerase. We're talking about an ancestor. What do we mean by that? Speaker 3 00:23:17 Well, it's an earlier version, a slightly simpler version of itself. Mm-hmm. <affirmative>, and I do commend the authors here because they did openly say that, Hey, you know what? We had to step in and help because the yield was so bad. Yeah. There's no way that these three parts would've found each other in the muck. Okay. Interesting. And so they came in and, and filtered out all the, all the junk and left behind the good parts, and they could find each other to, to assemble into a, a pseudo version of the ancestor. Mm-hmm. <affirmative>, except I skipped a part there. We've already, we've skipped over the, the forming of a complimentary rna. So first this thing has to form the compliment of itself, meaning all of the letters are the opposites. And you have to get that together. And then you have to form the compliment of the compliment. Speaker 3 00:24:06 Mm-hmm. <affirmative>. So there's a whole nother step that has to go through, which again, had a yield of about 1% per part, and you had to filter out all the garbage again and get the good parts, the three parts that are good to come together again. So the the final yield, then when you have 1% yield for each of three parts, and then you have to have the human come in and clean up the junk and pull those three parts together. And then you have to make a compliment to the compliment, which is three more parts that each have a yield of 1%. So it's kind of like six parts that each have a yield of 1% coming together, which again, would never make a successful business. So finally then you have, I guess you could say replicated the ancestor of this rib design. But wait, there's more <laugh> because after they got it together, they finally had a, a version that was complete. They recognized that it had nowhere near the activity level. It wasn't nearly as functional as the original. And that turned out to be, because as it replicated each piece, yes, it got the right length 1% of the time, but inside each piece there's those, you know, letters, maybe there was 60 letters in each of the pieces turned out letter by letter, the accuracy was only 92%. Speaker 2 00:25:28 Hmm. Okay. And that's, you know, for most people, Hey, if I get a 92% on my test, that's pretty good. I got an A. So wh why do you say 92 percent's the problem? Speaker 3 00:25:37 Well, 92% is not so good in, in a DNA RNA kinda world, because some of those nucleotides are very important to make it the active site or get actually function. So having 92% accuracy knocked the functional capability of this thing down by a huge percentage. But if you then had to go on to replicate, you know, come up with a second generation, now you're down from 92% to what, 80, 81%, something like that. And it just keeps degrading from there into what you call error catastrophe, that after a few generations, there's just nothing, no remnant left. That works at all. Speaker 2 00:26:16 Yeah. So 92% might sound good for my, uh, geography test, but if I'm trying to copy a, a program or a file on my computer, that's totally unacceptable. Speaker 3 00:26:27 Exactly. Yep. Or a book you'd hate to read a book that was 92% accurate. Letter by letter. Speaker 2 00:26:34 Yeah. <laugh>. Oh, and then a copy of that, that was only 92% of that. Yeah. Cascades pretty quickly, there's a statement in the paper. I don't know if this is what you're referring to, Rob, this, this, let me just read this sentence. It says, if the liase is assembled from three fragments that have been synthesized by the 38 dash six rib, there is an 8,000 fold reduction in activity. Speaker 3 00:26:56 That's the one fold. Sounds like broken to me. Speaker 2 00:27:02 Yeah. Okay. But it's Speaker 3 00:27:04 Important though that these, these authors, at least I give Gerald Joyce some credit here, because he did conclude openly, candidly, said that thus the fidelity of RNA polymerization should be considered a major impediment to the construction of a self-sustained RNA-based evolving system. Mm-hmm. <affirmative>. So I almost sense a little bit of frustration there that they've been working at this for 20 years or something and, and they're just hitting this brick wall that they just can't get anything close to being good enough to fulfill their vision. Speaker 2 00:27:37 Yeah. And I appreciate you saying that, Rob. I mean, we're, we have a little bit of fun with the challenges here that they're running into, but this is not some fly by night set of folks here. These are leading researchers in origin of life that have been working on this for decades. And so the kinds of challenges and problems that we're pointing out are not because these aren't smart folks, it's because these are challenges and problems that are endemic to this whole idea of getting a self replicated molecule up and running. Speaker 3 00:28:03 Yeah. And, and if I may <laugh>, if I may pile on a few more challenges that they don't even Speaker 2 00:28:08 Sure. Yeah. What, tell, tell us what else happened in this <laugh>. Speaker 3 00:28:12 One thing they don't talk about in the paper is the fact that all these RNAs have an expiration date. They tend to just degrade naturally over a few days time. And so you have to do this copying faster than it's gonna degrade, you know? Right. Things, things fall apart and you have to worry about that. And then there is the problem that Saul Spiegelman highlighted back in the sixties, that if you have a replicator like this and you go generation after generation, what you're gonna end up with is, is, is a parasites problem. That little fragments of RNA are the fastest to be replicated because they're short. Mm-hmm. <affirmative>, it's easy to faster to replicate them. So you end up with these, I mean, they're called parasites because they come in, it's almost like cancer. They come in and they get replicated quickly and they do nothing but use up all the resources you have Speaker 2 00:29:06 Take over the population. Yeah. Speaker 3 00:29:08 So that's a big problem. And then we all know that life couldn't exist without careful regulation. You can't just go on making stuff constantly using up all your resources with no regulation to it. So <laugh> somehow that had to develop also to tell us when we need to manufacture this and, and not just do it constantly. Speaker 2 00:29:29 Right, right. Yeah. And I was looking at something recently, another paper I was looking at. So here we're talking about a single polymerase, typical replication. Now this obviously is a little different scenario. So we're talking about living systems with dna, n a and r N A and the whole setup, but you're typically looking at a minimum of 40 proteins involved. And in some organisms up to 125 different proteins involved in the process of getting faithful replication. You mentioned the A, the poor yield B, the poor copying rate in terms of accuracy that they're achieving with, with this simple rib design. So it just degrades, I think your point about Spiegelman's monster is, is really important because the whole idea here of the r n A world is that we're gonna have a self replicating molecule that is going to get better and is going to do more things and is going to become more complicated and is going to achieve new, uh, activities or new features. And what we see in reality in the lab, in the best of conditions with assistance is that the thing degrades and eventually runs into nothing. I mean, it just sort of degrades it to nonsense. Speaker 3 00:30:38 And we have seen that again and again for, for a dozen years. Now, maybe I'm reading between the lines, but I sense in this paper that, uh, Gerald Joyce is beginning to be a little frustrated by, uh, all the, all the challenges. They face a lot of headwinds here, but they do indeed end up with a very provocative and encouraging title nonetheless. <laugh> Speaker 2 00:31:00 <laugh>. Yeah. Okay. Well, a, anything else you wanna mention as we kind of wrap up here, Rob, on this particular topic? E either this paper specifically or self replication generally? Speaker 3 00:31:11 Well, just to come back to the beginning to highlight that this is an absolutely essential functionality to have a purely natural process lead to the first life need. It's not just gonna be one molecule itself replicates we're talking evolution process. You would need millions and millions of different versions that all can self-replicate and all get better at it and, and gain information somehow along the process. So it should be not only easy to find a self replicator in a laboratory, but they should be just pervasive if this theory has any basis. Mm-hmm. <affirmative>, you, you should hardly be able to work with RNA without encountering Oh, yet another self replicating rna. These things just pop up all the time. <laugh>, that would be in line with the theory, right. That would be encouraging for them. Yes. Speaker 2 00:32:07 Yep. And yet no one has ever in the field or in the lab seen as self replicating rna. So here we, here Speaker 3 00:32:14 We are, and you can tell from this discussion today that there are nowhere near close to that, despite the claims that you hear in the titles. Speaker 2 00:32:20 Yeah. Let me read just a couple of quotes from the paper maybe to tie it off here. It says, for any realistic values, for selective advantage, and then they talk about the length that's required, and they say that the 38 dash six polymerase contains nearly 200 nucleotides and thus must be copied with an average fidelity of greater than 99.5%. You know, that's, that's what they recognize as required for the theory to work on that front. And then there was another final quote here. At the very end of the paper, it says, in seeking to surmount the error threshold and to achieve the self-sustained evolution of R N A, it will be necessary either to increase the fidelity of the polymerases rib substantially or to decrease its size substantially. Speaker 3 00:33:06 And those are conflicting requirements, I would say, because mm-hmm. <affirmative>, I mean, we know that life has much greater accuracy than this. And we know that life is very complicated and what it does. Yeah. And to try to dumb it down and make it super simple, I can guarantee you it's gonna get a lot less accurate. Speaker 2 00:33:24 Yeah. Right. Right. Okay. Well Rob, this has been super helpful to, to have you here today. I appreciate all your work on the long story short videos. This are really great. Again, encourage listeners to go check those out. You can go to YouTube and if you just type in discovery science, long story short and replication, it'll pop up with the video there. So encourage you to check that out. Uh, you know, this is an easy and a non-intimidating way to share the message with the friend if you kind of check out that long story short video. So thanks so much for being with us, Rob. Speaker 3 00:33:55 Thank you, Eric. Appreciate it very much. Speaker 2 00:33:57 Thank you for listening to this episode of ID The Future. To learn more about the Origin of Life, visit [email protected] or on your favorite podcast app. And as always, consider sharing a link with a friend. For ID the Future, I'm Eric Anderson. Thanks for listening. Speaker 1 00:34:14 Visit [email protected] and intelligent design.org. This program is Copyright Discovery Institute and recorded by its Center for Science and Culture.

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