Engineered Complexity in the Microbial World

Episode 2066 June 06, 2025 00:22:36
Engineered Complexity in the Microbial World
Intelligent Design the Future
Engineered Complexity in the Microbial World

Jun 06 2025 | 00:22:36

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Show Notes

On this ID the Future from the archive, host Jonathan Witt speaks to molecular biologist and professor Dustin Van Hofwegen about his research into the engineered complexity in microbial life. Hofwegen shares his research on the famous decades-long E. coli evolution experiment conducted by Richard Lenski, which showed the sudden appearance of an ability to utilize citrate after many generations. However, Van Hofwegen's own experiments demonstrated that this "evolutionary innovation" actually points to the intelligent design built into living systems instead of an undirected process like natural selection.
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Episode Transcript

[00:00:04] Speaker A: ID the Future, a podcast about evolution and intelligent design. Hi, I'm Jonathan Witt. I'm a senior fellow with Discovery Institute's center for Science and Culture. I actually oversee Intelligent design, the future, usually from behind the scenes. But today I'm here at a conference in Texas. I'm a Texan. I live in Denton, Texas. And it just so happens that there is an intelligent design conference here in Denton, Texas, by the shores of Lake Louisville. It's been beautiful weather all the time we've been here, and this conference is a little unusual. It's not kind of broadly open to the public conference. It's a conference that brings together biologists and engineers and looks at living systems. And I've got one of our participants here today who gave an excellent lecture, Dustin van Hoffwegen. Welcome, Dustin. [00:00:58] Speaker B: Yeah, that sounds great. Thank you. I'm glad to be here. I've been enjoying the conference so far this weekend, and I thought it was a great concept seeing engineers and biologists in the same room, and I just thought I had to participate in that. [00:01:11] Speaker A: Yeah, the basic idea of the conference is there's all kinds of amazing engineering in living systems. And so let's bring together engineers and biologists and see what kind of synergies created. [00:01:22] Speaker B: Exactly. Yeah. That was. That was the draw for me as well, because when I look at microbial systems, I'm looking at what it is that they're doing to engineer responses to their environment. And so I wanted to help develop that language with the engineers and try to figure out, can we come to a common language when we look at these biological systems which appear to be engineering their responses? [00:01:47] Speaker A: You know, one of the things driving the conference is this. This conviction that if you come to biology, you come to cells, you come to all the amazing things going on there with the design perspective. It's going to fuel innovation in terms of understanding what's going on, because you're going to be heading in there thinking, okay, there's a master engineer at work. Let me think in terms of engineering. Let me think in terms of reverse engineering. Do you see that paradigm as fruitful? [00:02:15] Speaker B: Yes, I do. A number of systems that I've looked at over the years of my career in microbial genetics is looking at how organisms are responding to their environment. And it looks like they have things like sensors and they have adaptation mechanisms built into them so that when they find themselves in situations that they are otherwise unable to respond to, what do they have to do in order to ensure their ability to survive in those situations? And so that to me was a very engineering based problem of watching what these organisms were having to do. And, and so the conference of bringing together the engineers and the biologists to help develop that language has been really, really helpful with articulating that. [00:03:03] Speaker A: Okay, let's turn specifically to your lecture. There was enough there, I think, for half a dozen podcast episodes. We're gonna do a lot of boiling down here, both cause of time and also because a lot of our listeners are driving down the highway after work. And so we're gonna try to keep it as simple as possible. [00:03:22] Speaker B: Okay, that sounds fair. [00:03:23] Speaker A: But at of your talk was this famous, at least among biology, intelligent design, evolution geeks. This experiment by Richard Linsky. Go ahead and tell us about that and then we'll kind of dive into what your research, the kind of light it shed on that. [00:03:40] Speaker B: Sure, yeah. Richard Lensky is a microbiologist at Michigan State University, and he famously set up this experiment 30 some years ago where he's allowed microbial organisms to continue to propagate independently of each other in 12 populations. And he's tracking them generation after generation. And in his experiments they've been able to go through, he is probably close to about 85,000 to 90,000 generations of E. Coli that he's been able to observe over the course of over 30 years and being able to watch what the organisms are actually doing in the environment that he has them in. And so the experiment is a very fantastic experiment, the way that he set it up, because we can actually see what organisms are doing in real time as they, as they try to adapt to the environment, as they try to engineer responses to allow themselves to, to grow much better in those environments. And so with that experiment, famously in his experiments, he saw after 15 years that the organisms had a very sudden appearance of this entire new biochemical pathway as the way that it was described, where they figured out the ability to grow on one of the nutrients that was in the media that they weren't otherwise able to grow on in those conditions. And so it was this really compelling evidence that these E. Coli organisms had developed this entire new ability that people hadn't seen before. And so it's, that's the way that the experiment was made famous. [00:05:22] Speaker A: What was the nutrient that they. [00:05:24] Speaker B: The nutrient is citric acid. So it's present in the media just as an artificial byproduct of just the way media used to be made years ago. But it's something that in the conditions of the experiment where the organisms are growing in aerated conditions like they're circulated in air. They usually don't need to use citric acid, so they don't grow on it. They're just growing on the little bit of glucose sugar that he gives them in the experiment. And then they grow a few generations and then they have to adapt or respond. [00:05:57] Speaker A: And so some of them develop this ability after years to start feeding off the. This citrate. Is that citric acid? [00:06:06] Speaker B: Citric acid, you use it interchangeably. [00:06:08] Speaker A: Yeah. And I want to read a quote that you had in your PowerPoint. This is Bob Holmes and this was in the major journal New Scientist. He said a major evolutionary innovation has unfurled right in front of researchers eyes. It's the first time evolution has been caught in the act of making such a rare and complex new trait. And as you said, when that happened it was interesting. But you point out in your talk, and you're not the only one Michael B. Has made this point, but I think it's worth making again. It's not quite as shocking as initially build. And you got very specific about it. And can you explain a little bit even before your own research, experimental results, which we'll get into a minute, why is it not quite as big a deal as build? [00:06:53] Speaker B: Exactly. Yeah. So of course that quote I pulled out just to show how influential and how impactful this experiment was seen. Yeah. Organisms growing on an entire new nutrient is incredibly interesting from an evolutionary perspective. But when microbiologists look at an experiment like that, we know that E. Coli does have the ability to grow on citrate. It's used in various metabolic cycles and they have the ability to use it in those, what we call the citric acid cycle. And if they get it into the cell, it's used in their metabolic processes. And the only difference is that in the conditions of the experiment, they didn't have a transporter, they didn't have the ability to bring that citrate outside of their cells into the cells and actually start to use it for energy. And so when I looked at that experiment as a microbiologist, I thought, well, all they have to do is turn that thing on. That's really easy for bacteria to do. Why did it take them 33,000 generations to do that? And so that, so let me pause here. [00:08:02] Speaker A: So it'd be, if this illustration is completely off base, it'd be a little like a, you know, a room and all of a sudden a light comes on after a few years and you're like oh, amazing. The room developed this ability and you're like. And you're like, it looks like a mouse or something bumped a light switch because it already had the capacity to have light. It was there. It just needed something to switch it on. [00:08:25] Speaker B: Exactly. And the E. Coli in these experiments, they have that light switch. It's just in the conditions of the experiment with oxygen present, that light switch is turned off. So what makes them turn the light switch on? Well, usually it's the absence of oxygen, but in his experiment, there is no oxygen, so the light switch would stay down. So what did they do? Did they break the light switch or did they give it a new light switch? Like, what's, What's. What's the experiment? Yeah, to do that with. [00:08:52] Speaker A: And so then. So just at a kind of analysis level, you knew that they were overblowing it, but then you went in and did some of your own experimental research. [00:09:00] Speaker B: It did. [00:09:01] Speaker A: And that eventually got published, am I correct? In the Journal of Bacteriology. [00:09:05] Speaker B: That work we did. Yeah. I was working in the lab of Dr. Scott Minick at the University of Idaho when I was doing my doctoral work. And we saw that experiment, we saw an opportunity to say that, wait a minute, there's a way for the organisms to do this. If we put them in a situation where they are stressed enough that they can do that, and if we put them in that situation, would they do it in a timeframe much less than 33,000 generations? And when we did the experiment, it turns out that they did, and they did it. Every time we did the experiment, they did. I think I isolated 46 times that they did it, and they usually did it in less than 100 generations. When we put them in a condition that said, all right, grow on this or you're not going to grow anymore. And they did it repeatedly. Almost every time we did the experiment, they did it. [00:09:58] Speaker A: Now, to me, that strikes me, and I'm just coming at this as a layman who's kind of studied this, not with a PhD in biology, but it strikes me as when Linsky. It happened in Linsky's lab, it was after thousands and thousands of generations. So you could kind of plausibly imagine all those generations, all the relatively big population size compared to mammals, and wow, he finally got lucky. Just like Darwinism says, if you have a big enough population, you have enough generations. But then when it happens in a hundred generations, when it just do or die, then you're like, that probably wasn't random chance achieving long odds because it had enough tries. There's something else going on here which seems to kind Of, I won't say kind of, it seems to strongly support your presupposition that it was just more of a switch that just needed to be. [00:10:49] Speaker B: Exactly. Yeah. We looked at the system as if it was, it had the ability to alter their response to that environment. We looked at the bacteria as not necessarily agents of change, but we looked at them as being able to respond to the change in a very rapid manner by using traits and functions and information that's already encoded within the genome. Would they be able to just activate the switches and activate the functions that they already have? And when we looked at it from that perspective, it said, this is a very simple, simple solution for the bacteria. All they had to do was provide a light switch. To use the nomenclature you're trying to do in bacterial systems, we call them promoters. So if we provide, would the organisms be able to provide their own promoter to that transporter and then start getting that nutrient into the system? And turns out when we did the genetic analysis, and when we analyzed the genetic analysis coming out of the Dr. Lenski's long term evolution experiments and the data that they published in Nature, the organisms in his situation and the organisms in our situation, they did the exact same solution. All they did was move a different switch or a different promoter in front of the transporter so that now they can turn on that transporter in any condition that they want it to. And so it allowed a situation for them to be able to continue bringing that nutrient into the cells. [00:12:22] Speaker A: You said 100 generations for these bacteria. How many days are we talking about. [00:12:26] Speaker B: For in the system of this? That's about 14 days. [00:12:31] Speaker A: So in 14 days we're getting this amazing evolutionary. Okay, so yeah, that sort of puts it in perspective. So I guess I could see somebody saying, well, you know, okay, maybe it wasn't a random mutation plus natural selection type of evolution, but hey, bacteria clearly show the capacity to evolve. So, hey, you know, we'll extend our evolutionary synthesis and evolution is still fine. How would you answer somebody that thought, hey, see, yep, blind evolution, this, this theory, this paradigm is still solid. We're just, we're just nuancing it a bit. How would you answer that? Objection. [00:13:09] Speaker B: Sure. I would say the organisms developed the strategy to respond to that situation by using the traits that they already had. They didn't develop anything that was drastically new. All they did was turn on a whole bunch of response mechanisms that said we need to start peppering the genome, start peppering all of our genes with all of these light switches. And then if the light switch Gets into the right spot. Even if it's a random insertion, they still upregulated or they still turned on all of these response mechanisms that said, throw out a whole bunch of light switches and put them in various spots in the genome. And then the ones that get the light switch in the right spot will say, those are the ones that are able then to grow in the experimental conditions. And so it's random only in the sense that that's where the location of all the light switches that they're sending out to the various parts of the genome, but turning on the mechanism to start sending out all of those light switches to start moving promoters. In bacteria, we call them transposons, but they start sending out transposons randomly throughout the chromosome and say the right solution is going to be the one that ends up growing when we do the experiment. [00:14:30] Speaker A: Yeah, I mean, if I had a. If I had a pickup that could run off of regular gasoline or it could run off of pure ethanol, and I discovered, oh, there's no gas. Oh, well, put ethanol in it. I wouldn't, you know, I would think, oh, there were some engineers that did some sophisticated work to make sure it could run off of gasoline and ethanol. I wouldn't think, you know, oh, that's, you know, somehow not. Does it need to be explained. And so for me, when I see that this, these E. Coli with this capacity, it tells me that it's more engineered. [00:15:02] Speaker B: Exactly. [00:15:02] Speaker A: There's more sophistication there than previously. [00:15:04] Speaker B: Exactly. [00:15:05] Speaker A: Thought. Yeah. [00:15:06] Speaker B: And we see that with bacteria, they have a whole bunch of different systems to burn all kinds of different fuels, to use that vernacular. They can burn like a car can burn ethanol and fuel and a whole bunch of different mixtures of gasoline. Bacteria can do that with a whole bunch of different sugars and fats and proteins and things like that. And they can do it with various carbon compounds like citric acid as well. So they have all of these abilities to use that material, Use all those available carbon sources. All those available fuel sources already present in the genome. [00:15:43] Speaker A: Yeah, it's fascinating. And we've been at this conference, we've been seeing biologists and engineers just throwing up example after example of just unbelievable engineering examples from biology. And what's exciting, too, is that you'll see an example like, wait, 10 years ago, I saw that, and it was amazing. And now it's amazing to another order of magnitude, you know, like what we're seeing with the bacterial flagellum, which, you know, new things being discovered there. So it's just A fantastic conference. A lot of this will be trickling out into more general circulation over time for a lot of it, probably first journals, but then also at conferences and articles. So it's exciting time. And one thing we have mentioned is, and some of our listeners may be already aware of this, there's a whole field of biology, right, Systems biology, where whatever the biologist believes personally about evolution or design, they approach the biological entity that they're studying from a kind of engineering, reverse engineering approach. And that's been extremely fruitful, hasn't it? [00:16:43] Speaker B: Exactly. Yes. And so hearing the language from all these systems engineers and these people that do real creative engineering for a living, it's been compelling to hear them use that language because they're talking about all these control systems and all these response systems and all these monitoring regulators, and those are the things that we do that I observe in these biological systems. When I look at how a bacterium like E. Coli operates, they're using these exact same principles of sensing the environment and responding to the environment and upregulating all these things that allows them to modify their response in. We call it systems biology. But I'm seeing the language of systems engineering having the exact same language, which is really compelling. [00:17:32] Speaker A: Tell us, this article, this Journal of Bacteriology article, do you remember the title offhand of that article? [00:17:41] Speaker B: Not to put you on the spot, my article? [00:17:43] Speaker A: Yeah, the one you did with Minnick. [00:17:44] Speaker B: What do you call it? Rapid Evolution of Citrate Utilization in E. Coli? Something along those lines. [00:17:51] Speaker A: Yeah. And we'll go ahead and put that in the episode description. We'll put a link to that article. But one other thing, quickly, before we close out, are there any other examples out there where something was kind of billed as, oh, this takes a really long time to evolve, but then it can. But then somebody went in and did some research and found that if you kind of create this do or die situation, then the evolution happens very rapidly and points to something that was already in the biological entity that had that capacity to throw a switch. [00:18:23] Speaker B: Sure. Are you asking about the antibiotic resistance example that showed. [00:18:28] Speaker A: Yeah, yeah. In the talk. Yeah, that was one that. [00:18:31] Speaker B: Yeah. I was showing some examples of looking at how an organism responds to the presence of antibiotics in a microbial system. We might call that a lethal selection. But you're putting the bacteria in a situation that says, there's this something here that's going to kill you. This is a stressful situation. What are you going to do to respond to that? And I use that as an example of a Little bit different type of mechanism where they're put in a situation where there's something that's going to respond and kill them in that situation. And so what are they going to do to quickly respond to the presence of that antibiotic? And the example I showed was some really clever microbial geneticists at Harvard that built a massive petri dish that's about 4ft by 6ft in length. And they exposed organisms. I can't imagine the room to have a huge petri dish in it. But they put just generic E. Coli in there with some antibiotics, and they put them in different lanes, different concentrations of antibiotic. That said, in the first one you can grow, in the second one you're going to die unless you figure out how to grow in that situation. Then the next lane is 10 times more antibiotic than they need. And the last one is a hundred. I guess there's a thousand concentration as well. And within 11 days, those organisms were able to grow in that concentration of 1000 times more antibiotic that would kill them in the first environment. And when those researchers went in and looked at the genes of the organisms that were able to grow on this antibiotic that was 1,000 times more concentrated, what they found was they just disrupted some of the targets of those pathways, of the pathway that that antibiotic happened to be responding to. It's something that we call folic acid synthesis. It's how they make their DNA, byproduct their DNA subunits to order to make these metabolic components in the cell. But by deleting some of the functions within that that pathway, they're able then to survive in that situation. So in 11 days, they develop the ability to grow on this high concentration of antibiotic. But it's not necessarily a creative way that they did that. Like, other examples show it was really just modifying the target, or in some cases, actually getting rid of the. The target of that antibiotic. And that's another principle of what we see in microbial evolution. It's like if you're in a situation where what you have is leading to your demise, then it's much easier for you to get rid of it. And it's much easier for you to just say, we don't need that right now. We're going to survive without it. Let's go on. But you're getting rid of large amounts of genetic information by doing that. [00:21:25] Speaker A: And which is what Behe talks about that in Darwin Devolved. [00:21:30] Speaker B: Exactly. Yeah. That's what his book was all about. Like, if somebody has the example he uses is if someone has a key to your house and you don't want them to get into your house anymore, well, you just break the lock and. [00:21:40] Speaker A: That key doesn't work it in the lock position and you know the key, you get worried you haven't created anything, but you solved a problem. [00:21:47] Speaker B: Exactly. [00:21:48] Speaker A: Well, we could talk a lot more about that one and maybe that, that could be a whole podcast unto itself sometime. We'd love to have you back. [00:21:55] Speaker B: That'd be fantastic. I'd love to. [00:21:56] Speaker A: All right. Well, thank you for joining us, Dustin. Again, if you want to dig into that journal article of his, we'll put it in the episode notes and keep an eye out for more about this conference. We hope to have some more material trickle from the conference onto ID the future, in the future. For now, we're going to close out. This has been Jonathan Witt. Thank you for listening. Visit [email protected] and intelligentdesign.org this program is copyright Discovery Institute and recorded by its center for Science and Culture.

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