[00:00:05] Speaker A: ID the Future, a podcast about evolution and intelligent design.
Have you ever wondered how our fingers and toes form during embryonic development? Welcome to ID the Future. I'm your host, Andrew McDermott, and today my guest is Dr. Jonathan McClatchy. To continue our ongoing series unpacking the many examples of intelligently designed systems in biology. Today we're talking about our digits. No, not our phone number, our fingers and toes, those dangly things on the ends of our arms and legs that make life so much more livable. Dr. McClatchy is a fellow and resident biologist at the Discovery Institute's center for Science and Culture. He was previously an assistant professor at Sadler College in Boston, where he lectured on biology four years. McClatchy holds a Bachelor's degree in forensic biology, a master's in evolutionary biology, a second master's in medical and molecular bioscience, and a PhD in evolutionary biology. His research interests include the scientific evidence of design and nature, arguments for the existence of God, and New Testament scholarship. Jonathan is also founder and director of talkaboutdoubts.com welcome Jonathan.
[00:01:21] Speaker B: Great to be here. Thanks for having me on again.
[00:01:24] Speaker A: So this interview is part of an ongoing series we're doing on ID the Future, unpacking numerous examples of design in biology. We've had discussions about the intelligent design of muscles, hearing the sexual reproductive system and the spicy problems it produces for a Darwinian paradigm. The blood clotting cascade that kicks in when we get injured. We've talked about the irreducible complexity of bacterial cell division and the bacterial flagellum. We've looked at the properties of carbon and other non mental elements that allow for complex life to flourish. And we've reviewed the life giving qualities of water and sunlight. So we've talked about it quite a bit, but there's still plenty to go. There really are so many examples of design and fine tuning in the natural world. We really could be at this a while. But today our attention turns to our digits, our fingers and our toes, and how the origin of our digits points to a process that requires foresight. You wrote about this
[email protected] so during early development, the hands and feet actually begin as solid webbed structures. Through a process called apoptosis, the tissue between them is eliminated, facilitating the separation of the digits. Now you include in your writing a useful metaphor for this process in your article. Can you share that with us?
[00:02:45] Speaker B: Sure. So this is a metaphor that I actually took from a paper called Shipping Organisms with Apoptosis by Suzanne and Steller. And they noted that the role of apoptosis can be compared to the work of a stone sculptor, who shapes a stone by progressively chipping off small fragments of material from a crude block, eventually creating a form. And so I thought that was a very apt illustration. Illustration for the way that our digits actually form through the process of apoptosis, where our digits, the space between our digits, actually dissolves through the process of programmed cell death, creating the forms that make up our fingers and toes.
[00:03:27] Speaker A: Yeah, it's a great analogy, and listeners bear that in mind as we go through this because it really helps you to understand the whole process. Okay, so remind us about the process known as necrosis and how it differs from apoptosis.
[00:03:44] Speaker B: Sure. So when a cell dies as a result of acute injury, the cell tends to swell and burst, and it releases its contents into the surrounding tissue. And this is a process known as necrosis, which is derived, of course, from the Greek word necrosis, meaning dead. And it can result in an inflammatory response that can be damaging to the surrounding cells. Whereas, by contrast, when a cell dies by apoptosis, it's much more clean and tidy, if you will. So during apoptosis, the cytoskeleton breaks down and the nuclear envelope disassembles, and the genetic material gets broken down into tiny fragments, and the surface of the cell is modified such that it attracts macrophages that engulf, or phagocytose, at the cell before its contents are able to spill out into the surrounding tissue and cause damage.
[00:04:40] Speaker A: Okay, so we're dealing with a cleaner process, apoptosis. Now, the main question you're posing in your article is this. How could such a developmental process involving programmed cell death evolve in a gradual, incremental fashion without any awareness of where the target is? Let's keep that question in mind as we look at this whole process, how it's regulated and controlled. First, walk us through how apoptosis is initiated.
[00:05:07] Speaker B: Sure. So there are regions known as the interdigital mesenchyme, which are essentially the zones of undifferentiated cells between what will eventually become the digits. And it's here that apoptosis is initiated by signaling molecules. So, for instance, bone morphogenetic proteins.
BMP for short. It's a helpful abbreviation.
So these are secreted signaling molecules that are critical for inducing apoptosis in the cells of the interdigital spaces. And knocking out these BMP molecules has actually been shown to result in webbed feet in chickens. And these BMP's are upregulated in the regions between the forming digits. And this results in cellular death and tissue regression. These BMPs bind to receptors on the surface of target cells in the developing limb bud. And this in turn activates intracellular SMAD molecules, which translocate to the nucleus and regulate the expression of pro apoptotic and anti apoptotic genes. For example, pro apoptotic genes such as BAX and BAC are upregulated and anti apoptotic genes such as BCL2 are down regulated. And that facilitates cell death in areas where tissue needs to be removed. And the activity of BMPs is regulated by antagonists such as noggin, which binds directly to BMPs, forming a complex that inhibits them from interacting with their receptors. And this makes sure that apoptosis only occurs in the interdigital spaces while preserving the cells that will form the digits.
[00:06:49] Speaker A: Okay, all right. And as you were explaining that. I was, it was. I was reminded that, gosh, our listeners could be tuning into an engineering podcast. You know, there's so many similar terms used to describe what's going on biologically, it's quite amazing. Now, a family of proteases called caspases comprise the molecular machinery responsible for apoptosis. Tell us about these executioner caspases.
[00:07:16] Speaker B: Sure. So.
So as you said, there's a family of proteases that are known as caspases comprise the molecular machinery that carries out apoptosis. And these proteases are initially produced as inactive precursors known as procas bases. In response to apoptosis inducing signals, they are activated. And executioner caspases are responsible for dismantling essential cell or proteins.
These are themselves cleaved and thereby activated by initiator caspases.
And one executioner caspase targets for destruction. The lamin proteins that comprise the nuclear lamina, resulting in its disintegration. And this facilitates the entry of the nucleases into the nucleus where they degrade the cell's DNA.
Other targets of execution of caspases include the cytoskeleton, other critical cellular proteins as well.
[00:08:12] Speaker A: Okay, you know, something I found very interesting is that caspases are initially produced as inactive precursors called. Guess. You guessed it right. Procast spaces. Pro meaning in front of or before. What are these procast spaces doing while they wait for the signal to initiate cell death?
[00:08:31] Speaker B: Sure. So in active procast spaces roam, and they are in wait for a signal to activate the death program and kill the cell.
And so they have to be, of course, as you might gather Very carefully controlled and regulated. The BCL2 family of proteins is responsible for regulating caspase activation. Some of these proteins promote activation of caspases and apoptosis, while others negatively regulate these processes. Two essential proteins for promoting cell death are BAX and bac. And these proteins trigger the release of cytochrome C from the mitochondria. And other BCL2 family proteins sequester apoptosis by inhibiting BAX and BAK from releasing cytochrome.
And critical to cell survival is the balance between the activities of the pro apoptosis and anti apoptosis BCL2 family members.
[00:09:25] Speaker A: Yeah, yeah. Which we'll touch on again shortly. Now, this idea of cellular elements being in an inactive state until they receive the signal to activate is really a hallmark of engineering of design. With the end in mind, it's looking ahead at a future function and putting in place what will be needed to produce that function. Now, you note that a cell's death program can be initiated in a couple of different ways. Tell us about that. And which one is associated with our digits?
[00:09:55] Speaker B: Sure. So there are two ways in which the cell's death program can be initiated. So there's the intrinsic pathway, and there's the intrinsic pathway. And the extrinsic pathway is initiated by external signals, as the name suggests, through the binding of ligands to death receptors on the cell surface, whereas the intrinsic pathway is triggered by signals from within the cell itself, again as its name suggests.
And the formation of digits, which is what we're discussing here, is associated with the intrinsic pathway.
[00:10:31] Speaker A: Okay. Now the activity of caspases must be carefully controlled, otherwise cells would not survive. And this presents another conundrum for their origins. How could they arise without a mechanism in hand for holding them in check until required? Do Darwinists have an answer for that?
[00:10:48] Speaker B: No. I believe this represents actually a formidable challenge to evolutionary explanations of their origins.
[00:10:55] Speaker A: Okay, do they even attempt to answer this? I mean, do they throw in co option as a. As a way to push back on it? Or do they have anything I haven't.
[00:11:04] Speaker B: Seen in the literature a cogent explanation to give or attempt to give a detailed account of the origins of these cast bases? As you rightly pointed out, how could they arise without having already simultaneously a mechanism in hand for holding them in check? And so this is, I think, a very difficult conundrum for an evolutionary explanation of their origins.
[00:11:28] Speaker A: Yeah, well, you have an image in your article and listeners will link to that in the show notes for this episode so that you can go back and look because you got to look at this stuff, you got to wrestle with its complexity, you got to get eyes on it. But you have an image in your article of a wheel like structure called the apoptosome. What part does that apparatus play in the process?
[00:11:49] Speaker B: Sure. So upon release of cytochrome C that I alluded to earlier from the mitochondria, the cytochrome C molecules bind to ApuF1, which stands for apoptotic protease activating factor 1. And this protein has a specific region called the WD40 repeat domain that interacts with cytochrome C. And this binding induces a conformational change in APF1, which allows it to ligamerize. The APF1 monomers does assemble into a large heptameric complex known as the apoptosome.
This wheel like structure serves as a scaffold for further recruitment of PROCAS base 9 molecules. Within the apoptosome, the proximity of multiple PROCAS base 9 molecules results in their autocleavage and activation. And this induces a caspase cascade involving the activation of downstream effector caspases such as Caspase 3 and Caspase 7. And this ultimately results in programmed cell death.
[00:12:50] Speaker A: Okay, and it has that unique shape just because of how it folds. Is it a collection of proteins? Is that what this structure is?
[00:12:59] Speaker B: Yes, exactly. It's a complex.
[00:13:01] Speaker A: Okay. Yeah, it really is a beautiful structure. Listeners, I encourage you to take a look. Well, let's go back to the metaphor you offered early in the discussion, likening the process of apoptosis to stone sculpting. An actual stone sculptor has a vision of the final form, the ability to visualize a distant outcome. Can natural selection do the work of a stone sculptor?
[00:13:26] Speaker B: So an actual stone sculptor has a vision, of course, of the of the final form, or the ability to visualize a distant outcome. Whereas a feature of natural selection, as you know, is that it lacks foresight, it lacks awareness of complex angles.
How can a mindless cause select for a process of carefully regulated programmed cell death during development without knowledge of the target? It seems counterintuitive and strikes at the very heart of the evolutionary rationale or evolutionary process.
Natural selection is blind to complex end goals. And so how could natural selection preserve a process of programmed cell death, which is a destructive process, without knowledge of where the target lies?
[00:14:17] Speaker A: Yeah, because you have to keep that process in check, you know, because unchecked cell death program, you know, equals just death all around. And it just really doesn't make sense. But it's a Conundrum for sure, for a Darwinian paradigm. Well, Jonathan, why is intelligent design a more adequate explanation for the origin of our digits?
[00:14:40] Speaker B: Well, it would seem to me that any process that is capable of producing this sort of mechanism would have to be a process that has intelligence and foresight.
As I said before, the ability to visualize complex higher level objectives, which are characteristics that have been uniquely associated with a conscious mind. And so I think that there's a top heavy likelihood ratio that these sorts of features are not particularly surprising supposing a mind is involved that can visualize complex higher level objectives, but are wildly surprising supposing that no mind is involved. And so in view of that top heavy likelihood ratio, I'm very heavily inclined to favor a design hypothesis.
[00:15:22] Speaker A: Right. And one of the things that I like about our discussions and about your articles at Evolution News is that you're helping to build that cumulative case. I mean, if it was just about our digits and, you know, just about this one system, then, okay, you know, you might put that down to coincidence. But when you start adding it all up, you know, when you start building that cumulative case about all the different systems in biology that have these hallmarks of design and irreducible complexity, you, you end up, you know, overwhelmed. And if again, if you go back to that, that scale, you start to see which part of the scale is tipping, you know, and heavier. So.
[00:16:05] Speaker B: That's absolutely right. And the Bayes factors, which is the likelihood ratio of the probability of the evidence given the hypothesis, in this case of design versus probability, that same evidence given the falsity of the hypothesis, these Bayes factors multiply together. And so the evidential force multiplies exponentially with each successive example. And so there is a real power, I think, in developing the argument as a cumulative case.
[00:16:31] Speaker A: Yeah. And listeners, if you, if you caught what Jonathan just said, he talked about the Bayes, you know, theorem, Bayes logic, Bayesian logic. You know, if that's foreign to you, Jonathan and I actually did an introduction to Bayesian logic as it pertains to Intelligent design. Just go back and look for that. Just search Bayes or Bayesian B A Y e s@id the future.com and you'll find that. Because I thought that was a really accessible introduction to how we can look at this likelihood ratio of the evidence and watch it mount up in the case for Intelligent design. Well, Jonathan, I didn't have this, you know, listed as a question I would ask you, but just, just for kicks, I mean, it's kind of obvious. I said that, you know, it would be hard to live without these digits, you know, our, our fingers and toes. But just off the top of your head, why are these digits so important to us?
[00:17:30] Speaker B: Well, of course they allow us to pick things up and engage in fine motor movements. We can.
So there's many things that our fingers and toes allow us to do that we wouldn't be able to do otherwise. Writing with a pencil, for example, is kind of hard to do if you don't have any fingers.
[00:17:49] Speaker A: So yeah, and you, you have the privilege of watching your young child right now be, be all into things with their fingers and toes. And I bet that's a rewarding experience and sometimes annoying probably when they pick up things they shouldn't. Yeah, I know, I remember that, that phase.
But yeah, I mean there's, there's no question that we couldn't get by without these. And so it's good to kind of probe the origins and really look at, you know, whether a Darwinian process could, could produce these amazing things that we hold dear. Well, Jonathan, thank you for joining us today to discuss this. You promise you'll be back, of course, to keep on going with our series.
If you do want more of Dr. McClatchy's articles on these topics, of course you can go to Evolution News. That's our powerhouse website that is updated on a daily basis with multiple new articles commentating and reporting on the news about intelligent design and evolution. Jonathan is writing regularly there. That's evolutionnews.org and if you want a bigger picture of everything that he's into and all his research interests, you can of course go to Jonathan McClatchy.com. try spelling McClatchy. Good Scottish name there. You don't want to get confused with that. M C L A T C h I e McClatchy.com Jonathan McClatchy.com well, Jonathan, thanks so much and we'll talk to you again soon.
[00:19:23] Speaker B: Thank you. Great to be here.
[00:19:25] Speaker A: Now, if you enjoy what you're hearing on ID the Future do help us reach new listeners by leaving a five star review on Apple Podcasts and forwarding an episode to a friend. And remember, in addition to all the major podcast platforms, id the future is available on YouTube as well. Subscribe to the Discovery Science Channel to get your fill of interviews, animations and original video series as well as every single episode of ID the Future. You can get all
[email protected] discoveryscience channel. That's the actual URL discovery science on YouTube for ID the Future. I'm Andrew McDermott thanks for joining me. Visit us at idthefuture.com and intelligentdesign.org this program is copyright Discovery Institute and recorded by its center for Science and Culture.
