Listener Questions #37

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Price may rise during contract, season, season, apply, check availability at gigaklear.com. Bodies contain blood, bones, muscles and everything in between. How is this all controlled at the level of the gene? How many unique cell types are inside of me? I count 83. Do you agree? Do clever tools require thumbs that neatly oppose? Or could alien minds build ships with tentacles? Or who knows? Whatever questions keep you up at night, Daniel and Kelly's answers will hopefully make it right. Welcome to Daniel and Kelly's extraordinary universe of alien biology. Listener questions episode number 37. Hi, Daniel. I study particle physics and aliens. Hello, I'm Kelly Wienersmith. I study parasites and space. And 25 years ago, I studied developmental biology. Do I remember any of it? Today we find out. It's Kelly on the hot seat today, answering questions from listeners about how everything works inside these crazy meat sacks we call bodies. We're just too big clear. I'm not actually relying on what I learned 25 years ago. I spent a lot of time reading about developmental biology again. But these are great questions and it was fun to revisit the field. And we thank you. Thank you. Thank you so much for sharing your curiosity with us. Sending in the things that puzzle you the things you would like to hear about. We thrive on your curiosity. It literally drives all of science. And so we're very glad to hear that you're curious about how the universe works. And we want to answer your questions about the universe. This podcast is not just a lecture. It's a conversation between you and us. Yes, and we are chatty people. So send us your questions at questions at Daniel and Kelly dot org or join us on our Discord channel. We have the world's best moderators. So our conversations are fascinating, funny and civil, which I love the civil parts and actually friendly place on the Internet. It's amazing. It's this is the only corner where you can find that. Friends, join us. And if you go to Daniel and Kelly dot org, you can find a link to our Discord page and you can join us over there. And if you've written to us and haven't heard back, sorry, please try again. You may have been caught in our spam filter. We really try to get back to everybody within a couple of days. So please, please, please reach out to us. We love to hear the things that make you wonder. And on today's episode, we're answering three fascinating questions from listeners focusing on how the human body develops and how alien bodies might develop as well. That's right. And we're going to start with two questions I got that were related. And so usually each segment, we air a question at the beginning of each segment. This time around, I'm going to air two questions together, because Ali and Brian had very similar questions, and then I'm going to spend two segments doing my best to answer them, and then I will air their responses at the end of segment two. So let's go ahead and listen to these fantastic questions. Hello, Kelly. Could you explain how DNA results into different cell behaviors? Like when a fetus develops, how does one cell end up as a muscle cell and another as a bone cell? Thank you. Hey, Kelly. It's Brian. As Daniel likes to say, this Rube Goldberg machine of a body is insanely complicated. I understand the basics of how cells differentiate and specialize based on which genes are turned on or off. But I've always wondered how many different types of cells there are in the human body. More specifically, I was hoping you could explain what actually makes them different. I remember building a cell diagram with arts and crafts in middle school, and it got me thinking, what about a cell's internal structure separates a cell in a tendon from a cell in a bone, muscle, artery, white blood cell, brain cell, and so on? As a related and follow up question, I'd also love to hear how new cells like know what to become in the first place, both as we grow in the womb and as we age out in the world. Thanks. Oh, boy. All right. So when you got these questions, Kelly, did you go, yeah, I wonder that, too. Or did you go, oh, here's a chance to learn developmental biology or did your stomach drop? And you went, oh, I should have paid attention in DevCell 30 years ago. I paid a lot of attention in DevBio. And if Professor Eileen Underwood were here, I think she'd tell you that I got an A in developmental biology. Nice. Yeah. But it was 25 years ago. And how much could have changed in 25 years? Maybe everything. You know, I think even if nothing changed, the probability that I could answer this question without doing more research is pretty much zero. So I did a lot of different research. One thing that was particularly helpful in case anyone's interested in learning more was I found a book called Life Unfolding, How the Human Body Creates Itself by James A. Davies. He's a professor of experimental anatomy. It's from 2015. So it's not, you know, from this year, but, you know, it's got some general principles that have decades of research behind them. So that's what we're going with. And so we have a lot of related questions here. How are we going to tackle this whole big question and all the sub questions? Yeah. OK. So I split it into four questions. I'm going to tell you what those four questions are, and then we'll tackle them one at a time. Great. So question one is how do cells in a fetus know what they need to become? How do cells in adults know what to become? How many cell types do we have? And what makes these cell types different? OK. And there is just no way the answer can be comprehensive because there is there is a lot of variability depending on what cell type you're talking about. And so my strategy here is to kind of give like an overview of strategies that can be used by cells to figure out, you know, for example, what they need to become, maybe dig into an example that I thought was particularly interesting. And if folks are just like, holy cow, we need like 20 more episodes on developmental biology, then I will find a developmental biologist to come on the show for 20 episodes or I'll buy a textbook and this will be a series. But for this point, it's got to be a bit of an overview. Awesome. Well, our friend, Matt Giordgiani, who's been on the show a few times, he's a developmental biologist. Oh, why didn't you tell me that sooner? I guess I should have let you know that I was spending the weekend with my nose in a developmental biology book, but my bad. Which is good for you anyway. All right. Well, why don't we start in question one and maybe a good way to start is for me to explain to you my understanding, which is probably wrong so you can get a sense for where we're starting. Yeah, great. So question one is how does a cell in a fetus know what to become? To me, this is a fascinating question because the fetus begins with one cell, right? You start with the egg and it's fertilized, but you have a single cell and everything that comes after that comes from that same cell. So literally every cell in your body, even though they're different kinds, nerve, muscle, brain, whatever, have the same origin, right? The same grandpappy or grandma cell. And so that means that they must have differentiated, but they have the same origin. So like that's confusing to me, like this one became nerve, that one became muscle. If they have the same ancestry, how does that happen? To me, that's the essence of the question. Yeah, it's fascinating. What's the answer? Keep going. That's a good start. The answer is I have no idea why this part turns into head and that part turns into tail. It could be environmental. Like there's more hormones over here as this thing is developing. And so maybe different genes are turned on. I mean, I know that every cell has a lot of genes and not all of them are used. Some of them are turned on and some of them are not. But I have no idea what's controlling which get turned on and which aren't. OK, all right, great. So that's where I come in. Great. So first, I'd like to start by noting that most of what we know here comes from things like studies in fruit flies and mice. And for ethical reasons, we can't do the kind of manipulative experiments we'd like to do on human fetuses that you'd like to do. Sorry, that we. That that you would need to do to answer these questions definitively. But that for ethical reasons, you will not do. Don't want to do that. You don't want to do because we are good people. Yes, I'm sorry. Bad choice of words there. I was reading my notes while speaking. I do not want to experiment on fetuses. OK. OK, so you've got this this group of cells. How do you start telling, quote unquote, telling these cells what they need to become? Yeah. Well, so very early on, one way the cells can start to figure out, like, you know, how do we know that we're different? Is that you can say, OK, well, some cells are on the inside of the ball and some cells are on the outside. So you start doing replication. And when you've got enough cells that there are some cells that are touching other cells on all of their sides, but some cells are not touching other cells on the exterior because they're on the outside of the ball, then they can say, OK, we're going to do something different. And so they start turning on different genes when they realize that they've got part of their body that's not touching other cells. So already we have a way for the environment to influence what the cell turns into. It's not just the recipe. Now it's input from the outside. Yes, right. And in things like insects, moms can get the ball rolling by doing things like putting stuff in the early embryo and that stuff in particular is what we call transcription factors. And I'm going to not use a lot of jargon because I know Daniel's eyes are going to roll back at his head and they might end up hurting his eyeballs. I was just going to ask, is there a Latin phrase for transcription factors we could use? Probably, but I'm going to try to avoid it anyway. But so so essentially what a transcription factor does is it turns on certain genes. And so what what they do is they dump a bunch of transcription factors into the early egg and as the cells start dividing, the cells that are, for example, at the bottom of the egg are going to end up with more transcription factors in them than the cells at the top because there's more transcription factors at the bottom than at the top. And that's how you start getting differences in the top of the egg from the bottom of the egg. Does that make sense? Hey, that was my basically totally uninformed guess. Oh, fantastic. All right. OK. So transcription factor, because transcription is how DNA turns into proteins. Are you transcribed DNA into proteins that must be related? Like, yeah, which ones get transcribed and which ones don't? Yes, I always forget translation and transcription. They're both T's, but I think yes. That's the first you translate, then you transcribe. OK. Yeah, they're not just T's, they're T are A. You see where I'm going. This is very complicated. But at the level we need to understand, it's just it helps determine what gets turned on and what doesn't. Yes. OK. All right. So those are early stage, what gets turned on, what doesn't. Our embryos also have structures that like literally just show up in embryos so that they can be there to release cues to tell parts of our body to start becoming things. And then as our embryos get more advanced, these structures are told to die and then they disappear. So they're only there to be like, you know, I'm just making up an example. Like, this is where the head goes. This is where the anus goes. And and then they disappear. They're just sort of like helping with layout stuff and then they go away. A lot of how things determine where they're going to go, though, are from cells releasing signals to impact what's happening with nearby cells. And so one cell will release a protein. And since Ali's question was about genes, I want to hammer home the point that when a cell is releasing a protein, proteins are coded for by genes. So there there is a cell that has a gene turned on. It's making a protein. It's releasing it out of the cell. And that protein is then going and like diffusing over to a nearby cell. And it's essentially telling that nearby cell, hey, turn on some genes. We got to do something coordinated together. And that's turning on genes in the nearby cell. And so by communicating with each other nearby, they're able to tell each other like, all right, we need to coordinate to make a muscle cell together, or we are going to be the heart. And so there's a bunch of signaling molecules that get used so that cells can communicate to one another. Does that make sense? Yeah. And so cells turn on these genes to make proteins, to signal to other cells that they need to work together. But something must have told that cell to start that signal, right? So something upstream from that. That's some environmental factor, like we're in this part of the body or we're close to the anus or there's this gooey thing on their outsides. Yeah, or it could be that the the structure that showed up just to tell us what we're supposed to become has started to release that signal. And, you know, so like very early on in development, there are cells with cilia, which are like hairs that are on the outside of the cell. And they are told to beat in a certain direction. And when they beat in that particular direction, they start sending a bunch of compounds in a certain direction so that cells that are in that direction get a lot more of this stuff than cells on the other side of the body or cells on the other side of the fetus. And this starts setting up the fact that not everything in our body is symmetrical. And so this sets up that like your heart goes on this side of the body and the stuff that's getting sent to one side of the body are things like transcription factors. So it's like your body has more of chemicals on one side that will tell your body like this is the side that the heart goes on and stuff like that. So there's different like so there's environmental cues that we talked about earlier, like I'm on the outside. There is cues like we are beating in a certain direction so that fluids in the embryo are getting sent in a particular direction. So this side has a higher concentration than the other side. And then there's cells talking to one another. These are all sort of various ways that your body can communicate where things need to go and what what needs to be happening. So there really is a very rich environmental context for all of these cells. The idea that how your body is built comes just from your DNA is missing a big part of the picture, right? Like these structures and the relative context and all these cues are a huge part of the recipe for building your body, right? It's not just encoded in your DNA. Well, I mean, so DNA most of this stuff is like proteins moving around and telling cells what to do and those proteins are made by the genes. And so, you know, none of this happens without the genes for the most part. I see. So for example, those structures you talked about, they say like put the mouth here, that's from proteins that are encoded by the genes. Yeah. So that structure needs to be made by genes and then they're releasing chemicals that say the structure goes here and those chemicals are encoded by genes. But there's a reason that structure is created over here in the mouthy area, right, and not over there in the finger area. And that comes down to environmental cues that happen upstream, right? So when I talked about the environmental cues early on, as I understand it, those environmental cues, like I am on the outside of the ball, are helpful for like maybe the first week or something very, very early on. But once you start getting to things like, you know, the head is here, the hynys here, stuff like that, a lot of that has to do with chemical cues. And those chemical cues are emanating from things like what's called the nodo cord, which is one of those structures I was talking about that gets made and then mostly disappears in humans. I think it still shows up as like the discs in between our vertebra. But it is hugely important in developmental biology for giving us cues for what goes where, but then becomes, you know, something that we mostly forget about unless our back hurts when we're older. So yeah, I think environmental cues become less important after the very, very early phases. And then it's a lot more about what cues are being found where. And that is coded for by genes. I see. But those later signals which come from genes are just like cascades from the original environmental cues, right? Otherwise, every cell is the same originally. So even though they're coming from proteins, which are encoded in the DNA, you can like trace them upstream to environmental cues early, right? Yeah, I think you could probably make that argument. The picture I have in my mind is like every cell is like going to the hardware store. Like, yes, you could make a cabinet or you could make a sculpture or whatever. All the things you need are there, but somebody has to decide like, what are we building today? Yeah. Yeah. I was looking for an example that I could give that would be like really satisfying. Like, here's how a liver is made. But the problem with trying to explain this sort of stuff is that a fetus has layers that are not easily analogous to, you know, like our human body, right? And so in order to explain it, it's hard to do without pictures and it's hard to do in a podcast and without introducing a bunch of jargon. And so to try to give a better sense for how this kind of thing works, I'm going to go ahead and use an example from an adult. And so this isn't a fetus, but this is going to give you a sense for how genes help cells decide how to behave and how to make decisions about what to become. Every cell in your body needs to be able to get oxygen and like relieve waste. But you like grow over time, right? And so or I grow over time. And when you grow and you end up with like more cells in an area, your body needs a way to say, OK, you know what? Actually, I need more blood vessels over here because there's like more cells and no they're no longer getting as much oxygen as they need. So how does your body know when an area needs more blood vessels? So what happens is that your cells make a protein all of the time and this protein whose name I'm not going to burden you with. Thank you Daniel's sake. This protein is actually constantly made. And when your cell is getting enough oxygen, your body just regularly destroys it. It's like, I got enough oxygen. I'm getting rid of this protein. I don't need it. But when you don't get enough oxygen, this protein stops getting broken down and it goes into the nucleus of the cell and it starts activating more genes. And one of the things that it does is it tells your cell, hey, we are in a low oxygen situation. You should stop multiplying. You should stop doing anything that isn't critical because we only have so much oxygen and then the other thing that it does is it gets the cell to start producing something else. And this is a signal that gets released from the cell. And this signal calls the blood vessels over to it. And it's like, you need to start heading over to me because I am not getting enough oxygen. And so now it starts growing towards the cell that needs more oxygen. And once that cell starts getting all of the oxygen that it needs, it goes back to destroying the protein that it was making, just like it usually does. So as I mentioned earlier, when it has enough oxygen, it just regularly destroys this protein. And so now that it's got as much of the protein as it needs, it just destroys it. It's got the blood vessel giving it as much oxygen as it needs. And so now it's fine. So does that kind of make sense? The body is building cell types of different kinds based on signals that come from the body itself. Right. That are coded for by genes and proteins are acting on genes to try to like tell the blood vessels that, hey, you need to make more cells to come over here to feed us. And then that is acting on the genes again to tell the cell, OK, I've got enough oxygen. I can go back to destroying this protein. And then the cycle stops. It's amazing to me how complicated this is. It's amazing to me that this ever works. And it's also amazing to me that it mostly always works. I know. Every time I learn more about biology, I'm terrified. Yes, right. OK. And you will be even more terrified when after the break, we start talking about stem cells in adults. Hey, this is Robert from the Stuff to Blow Your Mind podcast. Joe and I are both lifelong Star Wars fans, so we're celebrating May the 4th with a brand new week of fun, thought provoking Star Wars related episodes. Join us as we tackle science and culture topics from a galaxy far, far away, such as the biology of Tontons and Wampas on the ice planet, Hot or the practicality and corporate business sense of the Sith rule of two. Listen to Stuff to Blow Your Mind on the iHeart Radio app, Apple Podcasts or wherever you get your podcasts. Right then. Who's all in for cancer research? UK is race for life. Anglers, Ramblers, Climbers, Biversiders, Surfers, Gamers, Bikers, Hang gliders. Book clubbers. Let's go all in against cancer. All in to help fund life-saving research. Join our London events throughout the summer. Sign up now from just £14.99. Visit raceforlife.org. Prices vary by event distance and participant age. OK, we're back and we're exploring Kelly's understanding of developmental biology, as explained to a physicist in response to questions from listeners. And today, mostly, we're talking about how our bits know to turn into various bits. Kelly, where are we in the grander explanation? Alright, so now we are asking how do our cells know what to do after we're born? Like how does your body know I need to make another red blood cell, for example? You know, one thing your body could do is it could always just say like, when your skin cell is dying, your neighbor could be like, oh, we need to make another one. So I'm just going to replicate. But one problem with that is that if the skin cell next to you is dying, maybe that's because you just got hammered by some UV radiation. You just got a sunburn. And so maybe the neighbor is not in great shape either. So you probably don't want to be replicating using the neighboring cell all the time. And so what we do instead of constantly replicating with neighbors is we have what are called stem cells. And these are cells that we keep in very protected areas, so they're not likely to get damaged. We make sure that these cells have very active repair mechanisms so that they are keeping these cells in like the best shape possible. And these stem cells are able to make new cells that are in like the best shape that we're able to make given our age. But these stem cells in adults, we're not going to deal with fetal stem cells. We're talking about stem cells in adults. In adults, they tend to be able to make a smaller subset of cells. So for example, if you're talking about stem cells that you find in your bone marrow, they're able to make things like red blood cells, white blood cells. Do they make them or do they turn into them? Do they like split and then half of them becomes a red blood cell? Or are they like factories that pump out other cells? Yeah, so they create daughter cells, so they like split. And then the daughter cell could either become like a stem cell and continue to like stay in this safe area and do the splitting. Or they can then go on to become like a red blood cell or something else like that. So every cell in your body was a stem cell before? Some cells. So the other day we were talking about Langer Hand cells, which are like immune cells that are in your skin. Some of them are able to self-renew, which means they can replicate. So some of your cells can split and renew on their own. It's just that a lot of them don't. And so some of your Langer Hand cells in your skin, you know, replicated from a previous Langer Hand cell, which probably did come from a stem cell in your bone marrow. Does that answer your question? Yeah, I think that's fascinating also how cells can replicate a certain number of times and then they basically kill themselves off, right? So let's go through an example. So like you've got the lining of your intestine and the lining of your intestine is constantly exposed to like, you know, acid and enzymes and bile salts. It's a really harsh environment. You've got stuff scraping the lining of your intestine. And so the surface cells in mice last for about five days and it's, you know, reasonable to assume that it's something like that for humans. And these cells are probably not replaced by replicating, but they're replaced by stem cells. So what happens is inside the lining of your intestinal wall, you have compartments known as crips. And these are sort of like deep inside the lining of your wall and crips is such a great word. Crips like C-R-Y-P-T like the crypt keeper or crips like the gang members. Isn't that spelled the same way? No, that's C-R-I-P, Crip, like short for Cripple. Oh, is it? Yeah. That's not nice. You prefer the bloods? Is the crips or the bloods, Kelly? I'm not making any. Okay, you know what? We're moving on. It's Crips spelled like Edimosilium. Okay, Cript. Okay. And so I just went on the record saying gangs aren't nice. Anyway, so. This is why Kelly doesn't publish her address. That's exactly right. That's exactly right. So anyway, these crips are deep inside your intestine. They're protected by cells that are called panacells and these secret proteins that kill bacteria. There's also cells that secrete mucus around them. And so they're like very protected. And inside these crips, you get the intestinal stem cells. The intestinal stem cells are able to make more panacells. They're able to make the cells that like line your cell wall. They're able to make, you know, a variety of cells related to your intestine. And they split to produce daughter cells. The daughter cell will either decide to stay behind to create another stem cell if needed, or it will start crawling up the wall of the crypt and it keeps replicating as it goes. So this one replication can result in 64 additional cells that can become a variety of different cells. And then it crawls out into the intestinal wall. And by the time it makes it out into the intestine, it's mature enough to like replace the cells that are out there. And so that's how intestinal cell walls work. Fascinating. Yeah. And so one of the things that's interesting to me is how does the cell know what kind of cell it's in? What kind of cell it's supposed to become? Yeah. And in this book for the intestine, they didn't really know the answer, but we kind of know the answer for bone marrow. So can we switch to that system? Yeah. Tell me. Okay. So in your bone marrow, you have a different kind of stem cell. And for example, it's trying to decide how many red blood cells it needs to make. Red blood cells are the cells that carry oxygen to different parts of your body. Right. What I really want to know is, do I have enough oxygen going to all the different cells in my body or don't I? And so there's a part of your kidney that already is the sort of low oxygen part of your kidney. And it monitors how much oxygen that part of the kidney is getting. And if oxygen starts getting low in that part of the kidney, a hormone is released. And when that hormone is released, it goes to the stem cells in your bone marrow. And that hormone talks to your bone marrow stem cells and says, more red blood cells, please. Wow. And once you have a lot more red blood cells in circulation, you're going to have a lot more oxygen in your blood. And once you have a lot more oxygen in your blood, your kidneys stop releasing that hormone. And so your stem cells in your bone marrow stop getting the message that, hey, we need more red blood cells. So they make fewer red blood cells because they're not getting the message anymore. So it's like a feedback system. Yeah. So it's like a feedback system. And again, hormones are essentially sending like a message that then gets translated, you know, like at the level of DNA into, you need to start making a particular kind of cell. All right, Kelly, we're almost there. Okay. All right. You've taken this through fetal cell development and now adult stem cells. But now we want to understand like how many different kinds of cells are there and what really makes them different, like in the inner workings. Yeah. So first of all, I want to be clear that in the poem, I said, I count 83. Do you agree? Brian never said 83. I was just trying to make the poem interesting. But what? You were just searching for a rhyme. I was just searching for a rhyme because frankly, I'm not good at this, but I was having fun. So the estimate I found is that we have over 200 different types of cells, which is a lot. Yeah. But you know, when you think about it, like we've got different kinds of bone cells. We've got osteocytes, osteoclasts, osteoblasts. This is the part of the show where I revel in saying lots of different, you know, jargon. Well, Daniel World's eyes, we've got blood cells, platelets, red blood cells, white blood cells, which are like neutrophils and basal fills. We've got sex cells. We've got lots of different kinds of cells, right? I think you're being unfair. Go on. I'm not an eye roller. I don't roll my eyes. It's true you don't roll your eyes. It's true. You really don't. It's a metaphorical eye roll. That's right. That's right. You tell me verbally that you would prefer if I stopped doing it. And I guess I'm not a very good friend. But my question is, are these really clean categories? Because, you know, humanity likes to draw dotted lines across things that are really just a smooth spectrum. Are there really clean categories here? Are there 271? Or is it just a bunch of distinctions that humans made up? I mean, I think for a lot of these, you could make a very clean case. So for example, for muscle cells, you know, they argue that there's three different kinds, skeletal, smooth and cardiac, right? And so if you were to remove the cardiac muscle cells and replace them with skeletal muscle cells, your heart would stop and you'd die. So you'd be like, that type counts. And then if you removed platelets and then somebody cut you and you bled out, you'd be like, platelets probably counted as a real blood cell type. And so we do have a lot of types that are distinct. And I think you could argue for probably most of the 200 different cell types that they do distinct jobs. But could somebody else out there, alternative biologists, be like, I would draw different categories. Is there fuzziness there? Yeah, yeah, there could be. You know, I can imagine someone saying, oh, each kind of T cell is a different kind of cell. Yeah. So T cells are part of your immune response that goes after very particular kinds of bacteria and viruses. And I can imagine someone arguing that like the T cell that goes after a particular version of the flu is different than the T cell that goes after a different version of the flu. I don't have a list of all the 200 different cells that they named. Really? Because I wanted to hear all the names. One day we should get together and I'll read all the different names and then you can read me the names of all the particles and the subparticles and we can both have the most fun we've ever had. And nobody will learn anything. That's right. Yes. We'll both zone out five words in and it'll be amazing. All right, but I think the lesson here is that there are lots of different types, whether it's 200 or 400 or whatever. There's many, many different types of cells, but not 10 million and not two. Yes, that's right. Yes, that's a nice way to put it. Okay. Okay. And so what makes these different? First, I want to highlight what I think is the most interesting thing here, which is that they look very, very, very different. So for example, if you think about the cells in your brain, you've got like a neuron that has the spidery looking head parts and then the very long, thin connecting parts. And that looks so different than your red blood cell that looks like almost kind of like a Frisbee that bulges on both ends or something like that. This is a fascinating insight into Kelly's mind. Wow. You think neurons look like spiders. So when you look at somebody and you imagine their brain, are you imagining like a skull full of spiders? Yeah. What? No. I'm trying to overcompensate for the fact that I've used a lot of jargon. So I didn't want to say, you know, they've got dendritic, you know, ends and I'm just not doing a good job, I guess. To me, a neuron looks like an egg that fell on the sidewalk. It's like kind of like a big splat. Yeah. Okay. Egg that fell on a sidewalk. Like a pillow with like where someone punched their fist in the middle. No, I think your Frisbee was pretty good. Yeah. Okay. I agree with the Frisbee. Yeah. Oh, good. Good. All right. So they look very different. But are you going to say that they're actually very, very similar? No. Okay. They're very, very different. But what's amazing is that they all are made from the same genetic code. Right. You know, like you've got the same genome, but by turning on or off different genes, you end up with these cells that look incredibly different. Amazingly, like, you know, our red blood cells, they have hemoglobin, which is a molecule that like binds to oxygen and helps us carry oxygen throughout our body. Right. This is also one of the few cell types in our body where the nucleus gets like taken out at some point. So it doesn't have a nucleus. Amazingly though, in birds, it does still have a nucleus. Did you know that bird red blood cells have nucleuses? Nuclei? I didn't know that our red blood cells didn't have nuclei. Did you know that in the fetus, we have three pairs of kidneys? What? What? I know. That's crazy. That is crazy. And then two of them kind of disappear, although one of them sort of gets integrated into the male reproductive system. Yeah. Thank your kidneys. Next, never mind. Moving on. So, um, I recently saw my kidneys. Are you okay? I'm fine. But I had an ultrasound done and they usually tilt the ultrasound screen away from you. And I was like, Hey, can I watch? And they were like, we don't usually do that. I'm like, but I want to see inside of me. And so they tilted the screen over and I'm like, Oh, that's what my kidney looks like. Look, it looks like a kidney. Yeah. They were like, Oh, the physicist is surprised that the kidney looks like a kidney. And then I said, what's the weirdest thing you've ever seen inside a person while doing an ultrasound? And they said, we're not at liberty to discuss other patients. Oh no. So then I said, well, if you saw something weird inside of me, like a huge nest of worms, because I was channeling Kelly, Thank you. Yeah. Would you say something? And they were like, no. So then I was worried like, Oh my gosh, what are they seeing? That's why I wanted to see the screen. Yeah, I get that. I get that. Anyway, so you're telling me that the cells are really quite different that when you go to the human hardware store, the codes that let you build a red blood cell can let you build something really, really different like a nerve cell. That's really incredible. And I think Brian wants to know like, what is really different about these cells? Like how different are they on the inside, you know, their internal structures and inner workings? Yeah. So I struggled a lot to figure out the answer because the 200 different cell types differ a lot. Yeah. I mean, a lot of them have, you know, a nucleus, but you know, that's not even true for your red blood cells. I don't think that's true for your keratinocytes. And so we were talking about these when we were talking about the Langerhand cells in the previous listener questions episode. These are the cells that are like making up your outer layer of skin. I don't think they have nuclei either. Wow. You know, it's hard to like summarize what differs between them because we have so many different cell types that are so different. It's like saying, how does a bicycle differ from a Ferrari? It's totally different. Yeah. And you're like, well, where do I start? I mean, they need, they probably, probably most of them have mitochondria because they need a power source, like vehicles need power sources. And so I, yeah, I came up a little bit short trying to figure out an answer. So I give Brian 100 points for kind of stumping me. No, I think that's an answer. Right. The answer is there can be totally different kinds of cells, right? I think the question sort of assumes that there's some similarity that you can bring parallels between these various kinds of cells. But your answer is that the spectrum of cells are so different that there isn't really anything to say about what they might have in common. Or at least Kelly couldn't come up with anything clever to say. And so if other listeners would like to chime in, I'd love to hear, but yeah, that's kind of what I came up with. They're just, they're so different. And to me, that's what's amazing. Like the same set of instructions can come up with these cells that are so different. Yeah. Wow. Wow. That's what I've got. That's what I've got. The answer, Brian, is wow. The thing again that amazes me is that it works so well so often. Like before I was a parent, I was just like, yeah, of course people are born and then they develop big whoop. But then when I became a parent, I was like suddenly very invested in the specific development of this one critter. And then I was like, oh my gosh, all these complicated things have to go right for my boy to like grow into an actual human being. And all of a sudden I've had very little faith in any of that tapping. Please work. Please work. Yes. But it does. You feel very powerless. Right. Yeah. Yeah. All right. Well, let's ship these questions off to our listeners to hear if we scratched their developmental itch. That's right. Or if I have just made them crazy and now they feel like their brains are full of spiders. Hi again. Thanks for your explanation. I really enjoyed it and it helped a lot. Super interesting. I have been thinking about it and I have a few follow up questions. Well, I have many, but I will ask only two of them. You mentioned transcription factors being more concentrated towards the bottom of the egg. Do you mean that literally because of gravity or is bottom more about orientation like the side facing the uterine wall? And if gravity matters, would development of fetus be affected in zero gravity? And how do cells figure out left versus right during the development of fetus? Like what actually makes heart end up on the left side? Thank you very much. I love the show. Oh, great questions. Okay. Keeping me on my toes. So for the transcription factors and stuff that are at the bottom of the cell, it's not that they're just free floating at the bottom of the cell. So they're not, as I understand it, subject to things like gravity because that would be too susceptible to issues. So for example, if you had a fetus developing, you'd have to be careful to not jump around the time that your cells were dividing or something. And so I believe that everything is sort of held in place by things like spindles or just basically structures that hold the transcription factors and stuff in particular parts of the cell so that when the cell divides, you end up with different quantities of the transcription factors and stuff ending up in different cells. When the cells divide, one cell will end up with more of it than another cell because of the way that the quantities of the transcription factors were sort of divided up and held into place. So hopefully that wouldn't get messed up if you were in space and in a low or no gravity environment, but that might depend on whether or not the creation of those spindles that hold everything in place is impacted by having no gravity because that's just not an environment we evolved in or are adapted to. Okay. So then how does your body know how to handle the asymmetrical stuff so you don't have hearts on both sides of your body. Your heart is on one specific side of your body. And so how does your body know what side that heart should be on? So early in development, your fluids are moving in a particular way. So you have cells that have cilia, which are like little hairs that are moving things in a very particular direction. So the cilia are beating in a very particular direction and at a particular angle. And their way that they are beating, it ends up resulting in the fluids moving in one direction. And when the fluids are moving in that direction, they have a bunch of like good stuff in them. And because of the way the fluids are moving, that good stuff is getting used up. And so one side of your body is getting to use up that stuff. And the other side of your body, by the time it gets there, the good stuff has already been used up. And so one side of your body gets a lot of the signal and the other side of your body gets less of the signal. And this is essentially how your body learns that one side is going to be different than the other side. And we have done this because we've watched the cilia spinning and we've sort of modeled the way that they flow. And we also have created mutants that essentially move the cilia in the opposite direction and the organs in the body of those mutant animals show up on the opposite side that you would expect them to show up on, which is pretty cool. Thank you for the follow up questions. Hey, Kelly, you did an amazing job. After listening to this, I have to say I'm with Daniel. I am astonished that we function at all. Too many follow up questions to even know where to start. Keep an eye on your inbox for future episodes. Hey, this is Robert from the Stuff to Blow Your Mind podcast. Joe and I are both lifelong Star Wars fans. So we're celebrating May the 4th with a brand new week of fun, thought provoking Star Wars related episodes. Join us as we tackle science and culture topics from a galaxy far, far away, such as the biology of Tontons and Wampas on the ice planet hot or the practicality and corporate business sense of the Sith rule of two. Listen to Stuff to Blow Your Mind on the iHeart Radio app, Apple podcasts or wherever you get your podcasts. All right, next up we have Sarah from Louisville asking about opposable thumbs. Hi, Daniel and Kelly. This is Sarah from Louisville, Kentucky. My question is, are opposable thumbs necessary for the development of tools and technology? Would aliens need to have fingers and thumbs to make spaceships to visit us? Thank you and keep up the good work. Well I'm personally glad we have opposable thumbs for thumbs up, but we probably need them for other things too. What are opposable thumbs good for, Daniel? You can stick them into things, you know, I guess. You can pick stuff up. You can throw them at each other. You can write things down. Wait, you can throw thumbs at each other? Tell me about your thumbs, Daniel. How do your thumbs work? They're detachable, aren't yours? Oh my gosh, Kelly. Oh my gosh. Well, you're deficient. No, you can pick things up to throw at each other. You know, happy things like sandwiches and I don't know. That's not the right way to deliver a sandwich to a loved one, Daniel. Oops. They tend to disassemble when you do that. So already you get the sense that maybe I'm not fully qualified to answer this question. And you know, when questions come into the inbox, we have a little triage. I look at a question, I'm like, is this a Daniel question or is this a Kelly question? And this one, I was like, okay, well, it's kind of about biology, but it's also kind of about aliens and spaceships. So it was really on the edge for me, but because it had the word aliens in it, I was like, I'm going for it. I'm going to take this one. Uh-oh. I took a tiger beetle question that I actually think was a Daniel question. Uh, yeah. And it's been sitting on my desk for a long time. I might find some secret way to kick it to you. Do it. Bring it on. Put it in a sandwich and throw it over to me. All right. I'm going to toss it your way. My head full of spiders will take it on. Okay. Good. But I love thinking about this kind of question because while it's kind of about earth based biology, it's really about the larger context. Like why do we have thumbs? Could it have been different? Is it likely that we find thumbs on alien planets or are there like a vast number of ways that critters can grasp their tools on alien planets? Really fun and kind of philosophical. So we're not going to be totally constrained by biology today, which is why I took on this question. All right. All right. So how do other animals manipulate objects? Yeah. So some are really good. I'm trying to bring us back to biology if I can. Thank you. I know. Usually it's my job to bring us back on track, but, um, so what are thumbs good for? Right. What do we do with them? You're right. But it's not just that. We also use them to really apply a lot of power. Like we can squeeze really pretty hard with our hands and with our thumbs. And humans have been doing this for a long, long time, right? Our ancestors have had opposable thumbs for millions of years and you can find things like stone tools that are millions of years old. And the context of that boggles my mind. You know, imagine holding something in your hand that was shaped by a human like creature a million years ago. You know, purposefully to do a job, you know, hand axis and things like this. You can find them just lying on the ground. So cool. The other amazing thing about this to me is that a lot of those things were lying on the ground for a long time before anybody recognized what they were. You know, people are just like, Oh, they're just stones. And only upon further examination, you're like, this is not just a stone. This is an obvious pattern of work on it. This is a tool. It goes to show you how many things can be discovered just by changing your paradigm. And in some cases, they were taken from really far away. Like I was listening to a special episode of the rest is history and it was like a flint. I think it was like a piece of flint for making a fire that they realized wasn't found in that area and must have been carried a very long distance. And it's like, Oh my goodness, like this was a precious stone that had been. Anyway, yes, very exciting. One of my favorite stories about special stones is the one that looks like a human face. They found this pebble, which looks sort of like a human face. I mean, it's got like two eyes and doesn't look like anybody made it, but it's out of place geologically, which suggests that like somebody picked it up and like, Hey, look, this looks like org, you know, and carried it with them because it's like a rock that randomly looks like a person. And they're like, Hey, that's cool. Yeah. So it's not like creating art, but it's like found art, you know, from millions of years ago. To me, that's amazing. That's an amazing connection with like a person from a long time ago. Anyway, we're far off track, but we're talking about like the use of opposable thumbs. And I think this is the inspiration for Sarah's question. And is it possible to have the same kind of experience and build technology and spaceships and launch yourself into the universe? If you didn't have opposable thumbs, well, already here on earth, we see lots of options for grasping biology, right? Like Octopi, they don't have opposable thumbs, but they can definitely manipulate stuff. You can see videos of Octopi like opening jars, right? Even from the inside, like these are clever beings. And they very obviously have a precise sense of the world and how to manipulate it in great detail and with great intelligence. I love watching them open jars. It always blows my mind, especially when they're stuck inside the jar. Good job, guys. You made it out. I know I often can't open jars from the outside. Imagine opening from the inside. Like it's crazy. They might be smarter than we are. And then you have like crows. Crows only have a beak, right? There's no arms there at all. They don't have like clever thumbs on their feet. But with their beak, they can do a lot of really incredible stuff, right? They can solve puzzles. They can manipulate the world. Birds build really complicated nests for themselves. In fact, this weekend, I discovered an LBJ in my garage, clearly building a nest for itself. Oh, we've this. We're almost at the swallow time of year for my barns. So we're going to get the barn swallow nests. Nice. Yeah, they're really cute. They make a lot of poop, but they're really cute. And so I let them poop on my stuff and then just clean it up afterwards. But it's definitely a kind of engineering, right? They are building stuff. They are manipulating the world. I don't know if it's the kind of technology that can sort of boost yourself into space travel, right? There's sort of a threshold there where you build technology that can do things you can't do biologically. And then you can escape the limitations of your biology. I'm not sure if birds could ever do that, though. I'm pretty sure octopi could eventually. And then, of course, there's elephants, right? Their trunk lets them pick stuff up and poke it and manipulate it. And so it's definitely examples of critters out there who do not have thumbs, but have a similar ability to manipulate the world and apply their intelligence to make it the way that they need it. So then you might ask, is that enough for technology? Right? Like, could elephants have left alone develop factories to fabricate silicon chips at two nanometers, right? The way the humans have. Is that what we're really talking about? So make me think about what do you need for technology? Well, you need to be able to manipulate stuff, but you also need to be able to stick stuff together to like handle small bits of it to have like really fine control in like lots of different directions. I mean, we're talking about like artisanal work, you know, at an early stage in technological development, but you need like fine control, not just like roughly grasping things. But it also seems to me like you could do that in lots of ways. Like if you look at the spiders inside Kelly's brain, for example, right, they have lots of mandibles. Like they are building a web. Like that's definitely a way to have fine control over the materials in front of you. Oh, so just to clarify, we're just we're assuming that these organisms end up having the intelligence to do it. And we're just asking if they're able to manipulate it. But like so we're able to do things that are much more fine scale. OK, so like I've got friends who manipulate fruit fly brains. Yeah. And I think that some of them do that through computers where like, you know, they do a much bigger motion and then the computer makes that motion fine scale because we can't work at that fine scale. So I guess the, you know, the crow or the elephant would just have to make a device that could work on a finer scale. I think that's the crucial thing, right? If you can build some tech and then bootstrap beyond your biology so that the tech that you build can help you build other tech that can do things that you and your immediately built tech can't do. Right. And so I think to make that leap, you need to be able to build things using fine control. You need to be able to shape materials. You need to be able to handle small bits to build enough complexity into your tech so that it can then do things that you can't do. But, you know, also a worry there that we're thinking too narrowly, you know, that we're thinking about the way that we have progressed to technology, which is mostly like, you know, by constructing things. And so trying to think about how an alien civilization might find a completely different path to developing technology. Like rather than assembling a spaceship, could you imagine growing one? You know, like, OK, you don't need hammers and arms if you can like manipulate biology or some other kind of species and their development tinker with nature's technologies to manipulate it into like developing the objects that you need somehow. So you don't need the same sort of technological route that we have. Just, you know, one crazy idea. But the larger point is that, you know, we shouldn't be too constrained by imagining elephants or birds or octopi trying to recreate our path to technology because there could be lots of different ways to get there. Yeah. Yeah, agreed. And frankly, I think this is a really great opportunity for you to tell everybody about the great book that you wrote about imagining what aliens might be doing out there. Well, I hope that this is what inspired Sarah to write in the question. I did write a book recently called Do Aliens Speak Physics, which is all about whether aliens have followed a similar trajectory to understanding the universe that we have. Have they built similar explanations? Is our explanation unique and singular and inevitable? Or is it just one of many possible ways to explain the universe? Is our history of science different or is it common around the universe? These are the kind of things we explore in the book, which I had a lot of fun doing research for and writing. Thank you, Kelly, for giving me the opportunity to shout it out, though. I'm pretty sure everybody on the podcast has heard me talk about it many times by now. Well, Daniel does not have a brain full of spiders. And so it is a truly amazing book. Highly recommend. Thank you. So, you know, trying to think most broadly about what's needed, trying to like move away from the specifics of thumbs or even appendages and mandibles. You know, I think that any species to develop technology is going to need some kind of memory. And then you want some sort of way to pass your learning on to the next generation. So you can build on itself, you know, the reason that like your grandpa can't program the BCR or that I'm even making BCR references because I'm basically a grandpa is because technology advances, right? And the next generation becomes fluent in the technology and then builds upon it because we have this social learning. And the key to that is some kind of symbolic communication. The ideas I have in my head, don't die with me. I can write them down. I can communicate them somehow broadly so that I don't like show individual people how I make fire. We can store that information. It can last for a thousand years. This allows a sort of cumulative culture. I don't know if you need the specifics of like electronics, you know, which require like mining and manipulation of fire that would be hard for octopi to do. But I think most broadly, that's what you need is some any kind of memory and ability to communicate your learning to the next generation so you can get sort of cumulative understanding of how to manipulate the universe. I think that's really the essentials. Everything else I think probably an intelligent enough critter could learn to overcome. Excellent. Well, that was a fantastic answer. And let's see if Sarah thinks that the octopodes will be going to space when the humans are gone. Thank you for answering my question, Daniel and Kelly. It's fun to think that one day we might get to shake the tentacles of an alien that arrives in a biologically grown ship. All right, thank you very much, everybody, for sending us your questions. We want to hear from the spiders in your skull. What makes them curious? What do they want to know? Can they write emails? So write to us. Spiders at questions at Daniel and Kelly dot org are. Join us over on Discord. You can find an invite over at Daniel and Kelly dot org. We hope to hear from you. Thanks, everybody, for listening. Please go and do us a favor and rate the show on whatever podcast app you're using. It really helps people find us. Daniel and Kelly's extraordinary universe is edited by the amazing Matt Kesselman. He really is a wizard. You can also find us online on Blue Sky, Instagram and X, the end. Universe, come engage with us. You can email us at questions at Daniel and Kelly dot org. We really do want to hear from you. And you can find our website, www.DanielandKelly.org, where you'll also find an invitation to join our Discord, where everybody comes and talks about the amazing universe. And we also have the most amazing moderators. This is an I Heart podcast. Thanks for joining us. Hey, this is Robert from the Stuff to Blow Your Mind podcast. Joe and I are both lifelong Star Wars fans, so we're celebrating May the 4th with a brand new week of fun, thought provoking Star Wars related episodes. Join us as we tackle science and culture topics from a galaxy far, far away, such as the biology of Tontons and Wampas on the ice planet, Hot or the practicality and corporate business sense of the Sith rule of two. Listen to Stuff to Blow Your Mind on the I Heart Radio app, Apple podcasts or wherever you get your podcasts. Because you bought your robot vacuum on your Barclay card, you got zero percent interest for up to 24 months, which makes watching it hypnotically sweeping up your crumbs even more satisfying. Oh, Mr. But what you buy is your business. Helping you pay less interest is ours. Barclay card backing your future. Subject to financial status, new customers only. 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