WEBVTT - Can We Regrow Body Parts? 0:00:00.960 --> 0:00:04.360 Hey, welcome to sign Stuff, a production of iHeartRadio. I'm 0:00:04.400 --> 0:00:09.160 hoore Chim and today we're asking why can't we regrow limbs? 0:00:09.800 --> 0:00:11.600 If you lose an arm or a leg, we know 0:00:11.720 --> 0:00:15.160 that that arm or leg is not going to grow back, 0:00:15.600 --> 0:00:17.919 but we know there are animals in nature that can 0:00:18.040 --> 0:00:20.599 do that. If you cut off a starfish arm or 0:00:20.640 --> 0:00:24.520 a salamander's leg, it'll regrow a new one. There's even 0:00:24.560 --> 0:00:27.600 a fish that can regrow its heart if you cut 0:00:27.600 --> 0:00:30.760 off a piece of it. So how do they do 0:00:30.800 --> 0:00:34.120 it and why can't we do it? We're going to 0:00:34.200 --> 0:00:37.800 talk to several regeneration and animal experts and we're gonna 0:00:37.840 --> 0:00:41.800 find out if it's possible to activate that ability in people. 0:00:42.400 --> 0:00:44.479 So get ready to go out on a limb with 0:00:44.560 --> 0:00:48.839 us as we explore the regeneration of body parts. I 0:00:48.960 --> 0:00:52.080 promise it won't cost you an arm and a leg. 0:00:52.920 --> 0:01:00.640 Enjoy Hey everyone. To answer this question, I started by 0:01:00.640 --> 0:01:03.920 looking up a list of animals that can regrow their 0:01:03.920 --> 0:01:07.280 body parts. Not all animals can do it, but a 0:01:07.360 --> 0:01:09.680 few if you cut off a part of their body 0:01:09.920 --> 0:01:15.400 doultes regrow it back. On this list are starfish, flatworms, 0:01:15.800 --> 0:01:19.679 salamanders like the axe lotto and some fishes like the 0:01:19.800 --> 0:01:23.760 zebrafish and the Mexican tetrafish. We're going to talk to 0:01:23.840 --> 0:01:26.560 experts in each of these animals, and while we talk 0:01:26.640 --> 0:01:30.600 to them, we're going to learn three things. Number one, 0:01:30.800 --> 0:01:34.880 how these animals regrow their limbs, like what's their secret? 0:01:35.440 --> 0:01:40.560 Number two why humans can't regrow our limbs or can we? 0:01:41.240 --> 0:01:44.959 And three why do some animals evolve this ability and 0:01:45.080 --> 0:01:49.360 others don't? It seems like a pretty handy skill to have, 0:01:50.440 --> 0:01:53.080 all right. The first expert I talked to was doctor 0:01:53.240 --> 0:01:56.840 Andrew Wolff. Doctor Wolf is a researcher at the University 0:01:56.880 --> 0:02:03.000 of Maryland, Baltimore County who studies regenerate in starfish and flatworms. 0:02:03.600 --> 0:02:05.960 The first thing I wanted to know is can these 0:02:06.000 --> 0:02:11.120 animals really regrow anything? Well, let's start with the starfish 0:02:11.120 --> 0:02:12.559 and then we'll do the flatworms. 0:02:12.960 --> 0:02:16.359 So starfish are what are called a kinoderm, so that's 0:02:16.360 --> 0:02:20.000 a phylum of animals. So it's things like sea urchins, 0:02:20.040 --> 0:02:23.800 sea cucumbers, things called sea lilies or crinoids, where they 0:02:23.840 --> 0:02:26.680 also have sort of called feather stars that can move, 0:02:26.720 --> 0:02:32.440 and also brittle stars, so they're somewhat closely related. To vertebrates. 0:02:32.680 --> 0:02:35.960 What do we know about tissue regeneration in sea stars 0:02:36.000 --> 0:02:37.120 and sea urchins? 0:02:37.440 --> 0:02:42.360 So my work was understanding regeneration in their larvae. So 0:02:42.400 --> 0:02:46.080 they're very small, probably like a millimeter or so, very clear. 0:02:46.200 --> 0:02:48.880 They started to swim around the ocean for about two 0:02:48.880 --> 0:02:51.799 months or so until they metamorphous into the adult. So 0:02:51.840 --> 0:02:55.280 you can cut them in half, but those halves will regenerate. 0:02:55.520 --> 0:02:57.720 Okay, so you're saying, if you cut at the bottom, 0:02:57.720 --> 0:02:59.720 half will grow a top and the top will grow 0:02:59.800 --> 0:03:04.760 by and you'll get too identical animals. Yes, huh. And 0:03:05.160 --> 0:03:06.280 what about the flatworm? 0:03:06.440 --> 0:03:08.600 That's what I'm interested now. And so it not only 0:03:08.639 --> 0:03:11.680 does it regrow what's lost, it sort of reshapes everything 0:03:11.680 --> 0:03:14.639 else such that it's not out of proportion. So let's 0:03:14.639 --> 0:03:16.760 say you cut a worm in the three pieces like 0:03:16.840 --> 0:03:18.880 a top, of a middle, on a bottom. They'll all 0:03:19.080 --> 0:03:22.680 regrow what was lost, but the actual ending size of 0:03:22.680 --> 0:03:24.840 that worm is going to be smaller than the original 0:03:25.000 --> 0:03:29.240 wholeworm because if the tail regrows to be really small, 0:03:29.240 --> 0:03:31.000 the brain is going to be too big for the 0:03:31.160 --> 0:03:34.520 new body size. So now it needs to reshape everything 0:03:34.680 --> 0:03:37.840 to be in proportion to the new size that it is. 0:03:39.360 --> 0:03:43.120 So these animals will pretty much regenerate anything. If you 0:03:43.160 --> 0:03:46.560 cut them in half or in three pieces, each piece 0:03:46.760 --> 0:03:49.520 will regrow what's missing, and then you'll end up with 0:03:49.640 --> 0:03:54.440 almost identical copies of the original. Next, I talked to 0:03:54.520 --> 0:03:58.640 doctor Nadia f. Frobish, who is an expert in salamanders. 0:04:00.080 --> 0:04:02.880 My name is Nadia Flebish. I work at the Natural 0:04:02.960 --> 0:04:07.040 History Museum in Berlin and at Humboldt University. I'm a 0:04:07.080 --> 0:04:12.400 professor for evolutionary biology. Actually, everything that's alive can regenerate 0:04:12.480 --> 0:04:16.480 tissue to a certain degree, which is very convenient because 0:04:16.560 --> 0:04:19.359 otherwise I think we would all grow up with a 0:04:19.360 --> 0:04:22.919 lot of open scrapes and scratches as we go through childhood. 0:04:23.560 --> 0:04:24.880 That makes sense, Yeah. 0:04:24.920 --> 0:04:27.680 So of course we can all do wound healing to 0:04:27.800 --> 0:04:31.400 a certain degree, but some animals are even better at 0:04:31.440 --> 0:04:35.359 it than we are among vertebrates. So the animals that 0:04:35.440 --> 0:04:39.560 have a background, it's only salamanders that are the masters 0:04:39.600 --> 0:04:42.640 of regeneration. I think a lot of people are familiar 0:04:42.720 --> 0:04:46.560 with lizards regenerating tales and sort of throwing them off 0:04:46.600 --> 0:04:51.080 as a decoy for predators. But lizards, in contrast to salamanders, 0:04:51.120 --> 0:04:54.479 only get sort of like a fake tale back. It's 0:04:54.520 --> 0:04:59.400 more like a rotch of cartilage that's in there. And salamanders, 0:04:59.440 --> 0:05:01.720 if they lose their tail, they get a brand new 0:05:01.760 --> 0:05:06.520 tail with retever column and you know, spinal cord and musculature, 0:05:06.680 --> 0:05:09.679 so just like it was before. And they cannot only 0:05:09.720 --> 0:05:13.080 do that with their tails. They can also regenerate their limbs. 0:05:13.200 --> 0:05:16.440 They can regenerate the lenses of their eyes, a huge 0:05:16.480 --> 0:05:22.920 portion of their hearts, liver, so they're really really excellent regeneration. 0:05:23.360 --> 0:05:26.799 Pretty much any part of the body has been tested. 0:05:27.520 --> 0:05:30.680 Oh yes, this has been tested. Not any part, but 0:05:30.839 --> 0:05:32.880 a lot of the parts of the body. So they 0:05:32.920 --> 0:05:36.360 cannot lose their entire heart, for instance, and then regenerated. 0:05:36.400 --> 0:05:38.880 There still has to be like a critical amount left 0:05:39.080 --> 0:05:41.560 in order for regeneration to proceed. 0:05:41.400 --> 0:05:45.080 So the muscles, toenails, everything indeed. 0:05:44.880 --> 0:05:49.040 And sometimes it's really amazing because when the salamanders bite 0:05:49.040 --> 0:05:53.080 each other they can have quite gruesome injuries, so where like, 0:05:53.160 --> 0:05:55.719 for instance, the upper arm bone is sticking out and 0:05:55.800 --> 0:05:58.839 all the soft tissue is gone. Looking at it, you 0:05:58.839 --> 0:06:01.160 would think, oh my god, this is never going to 0:06:01.240 --> 0:06:04.919 grow back, but it does, and it's really quite amazing. 0:06:06.400 --> 0:06:09.839 And the last expert I talked to was Ezra Sengul, 0:06:10.279 --> 0:06:15.960 a graduate researcher at Oxford University who studies Mexican cavefish. 0:06:17.600 --> 0:06:23.200 I am Estra, and I use animal models, particularly Mexican 0:06:23.279 --> 0:06:25.239 cavefish and zebra fish. 0:06:25.760 --> 0:06:29.920 Okay, what do we know about tissue regeneration from zebrafish 0:06:29.960 --> 0:06:30.680 and cayfish? 0:06:30.839 --> 0:06:34.560 To start with zebra fish. Together with zebrafish, there are 0:06:34.600 --> 0:06:39.359 certain kinds of cavefish have regeneration catasity, and they have 0:06:39.400 --> 0:06:44.400 a remarkable precision. While doing that, they repair their sins, 0:06:44.800 --> 0:06:48.479 they replace it with an new functional one. They also 0:06:48.560 --> 0:06:53.800 regenerate their heart, spinal cord, retinas, and kidneys. They use 0:06:53.880 --> 0:06:58.160 them to study heart repay it in particular because unlike humans, 0:06:58.240 --> 0:07:02.279 the heart damage leads to starting in unspins, and zebra 0:07:02.360 --> 0:07:06.360 fish the heart cells replace that lost tissue. 0:07:08.400 --> 0:07:12.800 So all these animals basically have a superpower. If you're 0:07:12.840 --> 0:07:16.440 thinking of Deadpool or Wolverine from the Marvel movies, these 0:07:16.480 --> 0:07:19.680 animals can do what they do and they're real. Chop 0:07:19.720 --> 0:07:22.680 off leg and a new one grows back. Cut some 0:07:22.760 --> 0:07:26.600 of them in half, and both halves regrow into whole 0:07:26.840 --> 0:07:31.960 new organisms. I had a lot of questions. First of all, 0:07:32.200 --> 0:07:35.760 how do you even regrow a limb? And second of all, 0:07:35.960 --> 0:07:39.800 why can't we and other animals like cats and dogs 0:07:39.840 --> 0:07:44.120 and birds do this? To start, I asked our experts 0:07:44.240 --> 0:07:47.160 to give me a play by play of what actually 0:07:47.240 --> 0:07:51.200 happens when these animals are missing a body part. According 0:07:51.240 --> 0:07:54.480 to them, it's a step by step process, and it's 0:07:54.520 --> 0:07:58.760 pretty similar whether you're a starfish or a flatworm or 0:07:58.800 --> 0:08:03.600 a salamander. Step one is basically stop the bleeding. 0:08:06.480 --> 0:08:09.640 So the very first thing that's happening and that has 0:08:09.720 --> 0:08:13.120 to happen in order for regeneration to proceed is the 0:08:13.160 --> 0:08:16.200 wound healing. So the wound has to close over just 0:08:16.280 --> 0:08:18.920 like you know, we would have a wound if you. 0:08:18.880 --> 0:08:20.800 Think you're in the water. You don't want a bunch 0:08:20.800 --> 0:08:23.280 of stuff coming in and bacteria and all that stuff. 0:08:23.320 --> 0:08:26.160 So you have to heal the wound. There's different mechanisms 0:08:26.160 --> 0:08:28.800 that they do. Think like a purse string it sort 0:08:28.840 --> 0:08:31.600 of steals it, or you just have cells that spread 0:08:32.040 --> 0:08:35.079 that just close it up. Obviously, if you don't heal, 0:08:35.160 --> 0:08:38.760 then you're gonna fall apart. So there's a structural component. 0:08:38.800 --> 0:08:43.160 But that's the first thing, okay that makes sense. You 0:08:43.200 --> 0:08:45.960 first have to close off the gaping wound. That happens 0:08:46.000 --> 0:08:48.320 when you get an arm or a leg cut off, 0:08:48.840 --> 0:08:52.400 but that also happens when we get cut Our bodies 0:08:52.559 --> 0:08:55.800 also close the wounds. So why do we stop there 0:08:56.240 --> 0:08:58.400 and those animals don't. 0:08:59.400 --> 0:09:02.680 And it's really interesting is that the wound itself can 0:09:03.080 --> 0:09:06.199 signal to the rest of the body that regeneration needs 0:09:06.240 --> 0:09:09.000 to happen, big major thing that needs to happen for 0:09:09.200 --> 0:09:13.080 regeneration to proceed. So it's like a general response to 0:09:13.120 --> 0:09:15.439 a wound. But then from there it either says now 0:09:15.480 --> 0:09:17.040 I need to regrow or not. 0:09:18.360 --> 0:09:19.679 It says different signals. 0:09:19.880 --> 0:09:22.880 There's some sort of mechanism that they can detect that 0:09:23.160 --> 0:09:26.080 tissue was lost versus I just sort of made a cut. 0:09:26.400 --> 0:09:29.960 Something from the wound itself is able to recognize now 0:09:30.040 --> 0:09:31.679 I need to regrow ahead. 0:09:33.160 --> 0:09:36.679 So this is a key part of the process. Somehow 0:09:36.880 --> 0:09:40.679 these animals as bodies are able to tell it's missing 0:09:40.840 --> 0:09:43.960 a limb or a body part. There's some kind of 0:09:44.120 --> 0:09:48.000 signaling that happens that says, hey, this isn't just a 0:09:48.160 --> 0:09:51.360 flesh wound. We're missing an arm or a leg, and 0:09:51.400 --> 0:09:58.640 that calls in the cavalry. So once this signal goes out. 0:09:58.679 --> 0:10:00.920 You said it mobilizes things. What does that mean? 0:10:01.320 --> 0:10:06.240 So for regeneration, you need cells to make stuff right. 0:10:06.720 --> 0:10:09.439 Anything that you need that was lost needs to regrow, 0:10:09.640 --> 0:10:13.000 so you need to have cells for that. They have 0:10:13.280 --> 0:10:17.439 some sort of stem cells that mobilizes, stay, divide, then 0:10:17.720 --> 0:10:20.320 move to whatever they need to be, and they become 0:10:20.600 --> 0:10:22.200 the tissues that need to become. 0:10:22.559 --> 0:10:25.839 In salamanders, you have a few stem cells that are 0:10:25.880 --> 0:10:28.560 still in the system, but you also have cells that 0:10:28.720 --> 0:10:32.560 are sort of losing their identity that are sort of 0:10:32.960 --> 0:10:37.320 re entering the cell cycle to become something you're everywhere 0:10:37.320 --> 0:10:39.880 in the body, and then are recruited to that side. 0:10:40.240 --> 0:10:41.000 They actually move. 0:10:41.280 --> 0:10:45.000 Yeah, cells move a lot all the time. Actually, really. 0:10:47.440 --> 0:10:50.239 Okay. The next step is for the body to recruit 0:10:50.480 --> 0:10:53.800 a bunch of cells where you want the missing body 0:10:53.840 --> 0:10:57.360 part to grow. But these aren't just any cells. They 0:10:57.400 --> 0:11:00.040 have to be stem cells. If you haven't heard what 0:11:00.120 --> 0:11:03.760 these are. Stem cells are cells that can become any 0:11:03.840 --> 0:11:06.640 other kind of cell. If you think about it, the 0:11:06.679 --> 0:11:10.040 cells in your skin are very different than your eye cells, 0:11:10.480 --> 0:11:14.000 or your muscle cells, or your brain cells. That's because 0:11:14.040 --> 0:11:18.040 these are all cells that have become specialized parts of 0:11:18.080 --> 0:11:21.320 their DNA have been switched on or off so that 0:11:21.360 --> 0:11:25.240 they grow a stertin way. That's good because you wouldn't 0:11:25.240 --> 0:11:28.640 want your skin cells to suddenly turn into an eyeball cell, 0:11:29.080 --> 0:11:31.760 or you wouldn't want your brain cells to suddenly become 0:11:32.160 --> 0:11:35.560 muscle cells. Stem cells are cells that still have all 0:11:35.600 --> 0:11:38.440 their options open, and these are the cells that get 0:11:38.480 --> 0:11:42.679 called up to regrow a missing body part. Now, what's 0:11:42.760 --> 0:11:46.600 interesting is that some animals just have stem cells floating 0:11:46.600 --> 0:11:50.200 around their bodies, and some animals are also able to 0:11:50.840 --> 0:11:55.840 roll back their specialized cells to become stem cells. This 0:11:55.960 --> 0:11:58.160 part is going to be important later, but for now, 0:11:58.559 --> 0:12:02.120 just imagine a whole bunch of stem cells congregating at 0:12:02.120 --> 0:12:05.640 the wound site where the animal lost a body part. 0:12:08.960 --> 0:12:12.040 And they form this sort of massive cells at the 0:12:12.080 --> 0:12:16.840 wound site. Oh okay, last, it's a term for sort 0:12:16.840 --> 0:12:19.720 of they haven't fully met their fate. Yeah, they sort 0:12:19.720 --> 0:12:22.120 of accumulate at the wound site, which. 0:12:21.920 --> 0:12:24.520 Is sort of like a nose if you want to, 0:12:24.679 --> 0:12:27.319 like a cone on the end of the limb, which 0:12:27.360 --> 0:12:30.600 is the gross thoughe where all the cells are proliferating. 0:12:32.920 --> 0:12:35.360 Okay, so where you cut off a limb or a 0:12:35.440 --> 0:12:38.280 piece of heart or a fin A blob of stem 0:12:38.320 --> 0:12:42.120 cells forms, and from that blob grows the new part. 0:12:42.640 --> 0:12:45.400 We're gonna talk about how that blob knows what shape 0:12:45.400 --> 0:12:49.240 to grow into, which is super fascinating, and we'll talk 0:12:49.240 --> 0:12:52.640 about why us humans can't do any of this. But 0:12:52.720 --> 0:13:09.040 first let's take a quick break. You're listening to sign stuff. Okay, 0:13:09.120 --> 0:13:11.720 all right, So now we've got this massive of cells 0:13:11.760 --> 0:13:15.319 who are there to regrow whatever's missing. How do they 0:13:15.360 --> 0:13:16.160 know what to regrow? 0:13:16.840 --> 0:13:20.280 It's a great question, a very complicated question that we 0:13:20.400 --> 0:13:23.640 don't quite one hundred percent know the answer to. It 0:13:23.679 --> 0:13:27.000 depends on sort of what the tissue is. There's some 0:13:27.080 --> 0:13:29.160 sort of way that the animal is able to detect 0:13:29.480 --> 0:13:31.400 this is what's missing, and I think it's related to 0:13:31.480 --> 0:13:33.280 the idea of physitional information. 0:13:35.120 --> 0:13:37.000 Okay, we talked about how when you cut off a 0:13:37.080 --> 0:13:40.679 limb or a body part, these animals with this superpower 0:13:41.000 --> 0:13:44.600 start by closing the wound and then amassing a lump 0:13:44.600 --> 0:13:47.760 of stem cells where the body part used to be. 0:13:48.640 --> 0:13:51.719 The next question is how do these cells know what 0:13:51.800 --> 0:13:54.880 to grow into? I mean, you wouldn't want a tail 0:13:55.120 --> 0:13:58.360 or a brain to grow where your arm used to 0:13:58.360 --> 0:14:01.160 be and The answer is that every cell in your 0:14:01.200 --> 0:14:07.199 body gets signals about its positional information. That is, somehow 0:14:07.360 --> 0:14:10.960 cells seem to know where they are or where they 0:14:11.000 --> 0:14:13.600 should be in the body. And this is something that 0:14:13.640 --> 0:14:17.680 scientists don't fully understand yet, but it involves basically every 0:14:17.760 --> 0:14:23.120 cell talking to every other cell through special chemicals and molecules. 0:14:23.520 --> 0:14:26.960 And in this case, scientists have noticed an interesting pattern 0:14:27.320 --> 0:14:29.080 about how this works. 0:14:30.840 --> 0:14:33.520 The way it works is that the tip of what 0:14:33.720 --> 0:14:38.240 has been lost is sort of specified first genetically, and 0:14:38.280 --> 0:14:41.800 then you have sort of a dissonance between that very 0:14:41.880 --> 0:14:45.920 tip and whatever the stump area is, and that dissonance 0:14:46.040 --> 0:14:50.440 or that disconnect between those two genetic identities leads to 0:14:50.520 --> 0:14:54.120 that growth and to the exact replacement of everything that's. 0:14:53.920 --> 0:14:57.560 In the middle betweening. Wow, how does the tip not 0:14:57.760 --> 0:14:58.680 to turn into the tip? 0:14:59.360 --> 0:15:02.760 It's a genetic marker sort of their genes expressed there 0:15:02.840 --> 0:15:05.360 that are saying you are the tip now and like 0:15:05.480 --> 0:15:06.760 giving it that identity. 0:15:07.000 --> 0:15:09.560 Oh I see. It's like the distensios that are at 0:15:09.560 --> 0:15:11.520 the tip, they're like, okay, I don't see anyone else 0:15:11.560 --> 0:15:14.760 around us. We must be the tip exactly. That's fascinating. 0:15:15.040 --> 0:15:16.600 But then how do the cells in the middle know 0:15:16.880 --> 0:15:18.160 how to fill in the middle. 0:15:18.280 --> 0:15:21.920 Well, we haven't actually sort of researched all the details 0:15:22.000 --> 0:15:25.360 of that entire process. It's really it's sort of an 0:15:25.520 --> 0:15:30.440 interplay between cells dividing and genetic markers giving those cells 0:15:30.440 --> 0:15:34.560 positional identity, like saying this is where you are now 0:15:34.640 --> 0:15:37.320 you are a wrist bone, or you will be part 0:15:37.360 --> 0:15:40.200 of the wrist area, or you will be part of 0:15:40.240 --> 0:15:43.120 the musculature that is in the lower arm, kind of 0:15:43.200 --> 0:15:46.440 like that. It's an incredibly complex process actually, so it's 0:15:46.480 --> 0:15:48.160 quite amazing that it works so well. 0:15:49.840 --> 0:15:53.320 In other words, scientists don't quite know how the cells 0:15:53.320 --> 0:15:58.200 in animals that regrow body parts know what's missing or 0:15:58.320 --> 0:16:01.400 where they are or what shape they're supposed to. Mank, 0:16:01.920 --> 0:16:06.440 they just do, Like all of that is in our 0:16:06.520 --> 0:16:11.640 DNA to recognize, Oh, I'm between the tip, I'm about 0:16:11.640 --> 0:16:14.520 three quarts of the way between the tip and the shoulder. 0:16:14.720 --> 0:16:17.920 I must be you know, for our bicyle cell. 0:16:18.680 --> 0:16:21.480 Wow, Yes, it's all in the genetic markers. 0:16:23.720 --> 0:16:27.000 Like I said, it's a superpower. But as our experts 0:16:27.000 --> 0:16:30.040 point out, it's basically what happens when you grow in 0:16:30.080 --> 0:16:33.000 the first place, when you go from a fertilized egg 0:16:33.240 --> 0:16:37.160 to a fetus and eventually to a grown person. Somehow 0:16:37.400 --> 0:16:40.440 your cells know how to grow every part of you. 0:16:41.040 --> 0:16:45.240 Animals that regrow their body parts basically just reactivate that 0:16:45.400 --> 0:16:49.320 growing ability we all have in our DNA. Okay, the 0:16:49.360 --> 0:16:53.600 next big question is why don't all animals have this ability? 0:16:54.000 --> 0:16:58.520 How's a starfish, a flatworm, or a salamander different than 0:16:58.760 --> 0:17:03.720 us or dogs or cats or monkeys. Why can't every 0:17:03.760 --> 0:17:09.560 animal regrow limbs? What do you think it is that 0:17:09.640 --> 0:17:12.439 flatworms and starfish have the humans don't have? 0:17:12.840 --> 0:17:16.679 Yeah, the million dollar questions people always like, if you 0:17:16.720 --> 0:17:19.359 find something in the lab, can I just grind up 0:17:19.400 --> 0:17:21.240 the worms and inject it into my arm? 0:17:22.600 --> 0:17:23.960 You could be a starfish man. 0:17:24.320 --> 0:17:27.080 Yeah, I mean, hey, that wouldn't be too bad, I guess. 0:17:27.240 --> 0:17:27.359 So. 0:17:27.440 --> 0:17:30.840 One other thing that I haven't mentioned so far is scarring. 0:17:32.080 --> 0:17:35.280 It stops regeneration and a lot of context. So if 0:17:35.320 --> 0:17:38.280 you cut off your hand, God forbid, you have obviously 0:17:38.280 --> 0:17:40.160 a wound response, and it's going to heal and it's 0:17:40.160 --> 0:17:43.560 going to scar. When a lot of these other things regenerate. 0:17:43.600 --> 0:17:46.919 The starfish, the worms, even things like a salamander, an 0:17:46.920 --> 0:17:50.320 axle auto, they don't scar. It's a major sort of 0:17:50.400 --> 0:17:54.480 block of regeneration, and also that inflammation prevents a lot 0:17:54.520 --> 0:17:57.439 of these other steps that could be happening. There's little 0:17:57.480 --> 0:18:00.359 to no inflammation and a lot of these animals that 0:18:00.400 --> 0:18:03.399 can regenerate. So it's a relationship between scar and inflammation 0:18:03.520 --> 0:18:05.440 and ability to regrow. 0:18:07.040 --> 0:18:10.359 Ah, here's the first piece of the puzzle. Animals with 0:18:10.400 --> 0:18:14.359 the ability to regrow body parts don't scar and they 0:18:14.400 --> 0:18:18.240 don't get inflammation when they get cut. Making a scar 0:18:18.520 --> 0:18:21.000 is basically like patching a hole in your wall with 0:18:21.080 --> 0:18:25.240 a giant pile of bricks. Scar tissue is thick and 0:18:25.400 --> 0:18:28.240 tough and dense, and it basically gets in the way 0:18:28.600 --> 0:18:30.840 of regrowing a new body part. 0:18:32.480 --> 0:18:36.320 But these simpler animals, they just seal it up and 0:18:36.359 --> 0:18:37.440 that seems to be enough. 0:18:37.720 --> 0:18:40.879 They don't make a scar, basically, they do not, So 0:18:40.920 --> 0:18:43.879 that's one factor. The other fact that you said was inflammation. 0:18:44.000 --> 0:18:46.879 So when we get cut, it becomes inflamed, and how 0:18:46.920 --> 0:18:48.600 does that make things hard to regenerate? 0:18:48.840 --> 0:18:52.880 So it prevents any of the later steps from happening. 0:18:53.160 --> 0:18:56.920 It just prevents the ability of the tissue to regrow. 0:18:57.280 --> 0:19:01.159 It's not a happy state for cells to regenerate. No, 0:19:01.480 --> 0:19:05.960 that is not. What doctor Wolf is saying is that 0:19:06.000 --> 0:19:08.480 when we get an arm or a leg cut off, 0:19:08.680 --> 0:19:13.320 our body basically overreacts. It rushes to patch up the wound, 0:19:13.600 --> 0:19:18.200 building thick SCRs that block any regrowth, and it deploys 0:19:18.200 --> 0:19:22.320 the immune system, which makes everything so inflame that it 0:19:22.400 --> 0:19:25.960 prevents all the steps needed to regrow the body part. 0:19:26.400 --> 0:19:30.200 Cells don't revert back to stem cells, they don't divide well, 0:19:30.440 --> 0:19:33.159 so they don't form that block of generic cells that 0:19:33.240 --> 0:19:36.560 can then become the missing part. So now the question 0:19:36.680 --> 0:19:39.520 is why do we do that? Why do our bodies 0:19:39.640 --> 0:19:43.199 react that way, especially because at some point in our 0:19:43.240 --> 0:19:50.480 evolutionary history it seems we did something different. Okay, now 0:19:50.520 --> 0:19:53.720 the question is why can't humans regrow our lips or 0:19:53.760 --> 0:19:55.200 can we? Is that possible? 0:19:55.720 --> 0:19:58.560 Well, that's a question that always comes to all people 0:19:58.600 --> 0:20:02.480 who who work the regeneration. We always get that question, 0:20:03.080 --> 0:20:06.760 and that's not an easy question to answer because it's 0:20:06.840 --> 0:20:11.320 probably a combination of very complex factors that play the 0:20:11.400 --> 0:20:11.919 role in this. 0:20:12.480 --> 0:20:13.440 But we know from the. 0:20:13.320 --> 0:20:16.320 Fossil record that a lot of the ancient amphibians could 0:20:16.359 --> 0:20:20.760 regenerate too, and lungfish are the closest living relatives of 0:20:21.080 --> 0:20:26.560 os fourlimd vertebrates can also regenerate very similar to salamanders. 0:20:26.560 --> 0:20:29.840 So it is likely that regeneration as we see it 0:20:29.880 --> 0:20:32.920 in salamanders now is actually not something that is special 0:20:32.960 --> 0:20:37.160 to modern salamanders that evolved. But salamanders probably are the 0:20:37.200 --> 0:20:41.919 only living vertebrates today that can still regenerate. Back in 0:20:41.960 --> 0:20:46.400 evolutionary history, that was probably a widespread feature that then 0:20:46.440 --> 0:20:48.680 got lost in the course of evolution. 0:20:49.040 --> 0:20:52.320 Oh so interesting. It's not like they developed the special ability, 0:20:52.359 --> 0:20:56.560 they're the only ones who kept it exactly. Oh my goodness. 0:20:56.720 --> 0:20:59.399 What doctor Frobish is saying is that at some point 0:20:59.600 --> 0:21:06.920 basic all animals were able to regrow their body parts. Salamanders, starfish, flatworms. 0:21:07.040 --> 0:21:09.840 They don't have a superpower. It used to be a 0:21:09.960 --> 0:21:15.800 standard feature of all animals. But evolution at some point said, eh, 0:21:15.880 --> 0:21:18.600 you know what, let's not do that. It's not a 0:21:18.640 --> 0:21:24.040 skill some species evolved, it's a skill some of us lost. Okay. 0:21:24.280 --> 0:21:27.840 The obvious next two questions are why did evolution choose 0:21:28.080 --> 0:21:31.719 not to regrow limbs in species like ours? And if 0:21:31.760 --> 0:21:35.879 it's something we had but lost, could we bring it back. 0:21:36.440 --> 0:21:40.040 We'll answer both those questions after the break. We'll be 0:21:40.200 --> 0:21:51.800 right back, and we're back all right. We just learned 0:21:51.840 --> 0:21:56.000 a shocking piece of information, which is that scientists believe 0:21:56.400 --> 0:22:01.520 it's likely that basically all animals, these ambiotes, which are 0:22:01.560 --> 0:22:05.280 all for legged animals, used to be able to regrow 0:22:05.560 --> 0:22:08.639 missing body parts, but at some point in our evolution 0:22:09.080 --> 0:22:12.720 this ability was selected as not being the best for 0:22:12.880 --> 0:22:16.880 our survival, which is strange because you think that being 0:22:16.880 --> 0:22:20.840 able to regrow limbs would be a good thing. I mean, 0:22:20.920 --> 0:22:23.080 if you use a leg you can't really run away 0:22:23.119 --> 0:22:26.119 from a predator that's trying to eat you. So I 0:22:26.119 --> 0:22:29.600 asked our experts, why would we lose this ability? 0:22:31.280 --> 0:22:34.520 It seems like something so useful to have, right, that 0:22:34.680 --> 0:22:38.080 capacity to regenerate, but it also comes at the cost. 0:22:38.800 --> 0:22:42.959 So during the course of evolution, it probably was a 0:22:43.000 --> 0:22:46.040 matter of a trade off, and it's probably for that 0:22:46.280 --> 0:22:51.040 reason that regeneration was selected against during evolution at some 0:22:51.200 --> 0:22:54.800 point in amniote evolution. And it could have happened once, 0:22:54.880 --> 0:22:57.680 it probably had happened multiple times. 0:22:58.080 --> 0:22:59.760 Oh well, what's the trade of. 0:23:00.280 --> 0:23:04.600 Salamander's a giant cells, So they have like huge cells 0:23:04.640 --> 0:23:07.880 because they do have a lot of DNA that they accumulate. 0:23:08.000 --> 0:23:10.879 They just can afford to have all that DNA, But 0:23:11.000 --> 0:23:14.159 all that DNA has to be the transcribed, right, it 0:23:14.200 --> 0:23:17.240 has to be done for a second copy, and that 0:23:17.440 --> 0:23:20.080 caused a lot of energy and resources. 0:23:22.040 --> 0:23:24.720 Okay, the first reason we might have lost our ability 0:23:24.760 --> 0:23:28.119 to regrow body parts is that there's a cost to 0:23:28.280 --> 0:23:32.600 having that ability. First of all, it requires extra DNA. 0:23:33.160 --> 0:23:36.800 The program to regrow LIMB takes extra instructions and extra 0:23:36.880 --> 0:23:40.520 genes that can come at a cost, especially if you 0:23:40.560 --> 0:23:45.679 want to move faster and have a faster metabolism. I 0:23:45.720 --> 0:23:48.760 wonder if what you're saying is that at some point 0:23:48.840 --> 0:23:52.119 in our lineage, the evolution pressure was to like, hey, 0:23:52.240 --> 0:23:54.760 let's make things more efficient. We don't need all this DNA, 0:23:54.880 --> 0:23:58.159 and maybe one of the cuts was our ability to regenerate. 0:23:58.520 --> 0:24:01.479 Yes, that's it. So it's not just that we lost DNA. 0:24:01.600 --> 0:24:05.000 It's also that we have to go through cell cycles 0:24:05.080 --> 0:24:07.760 at a certain speed in order to keep our very 0:24:07.840 --> 0:24:12.120 high metabolism that allows us to run really fast, to 0:24:12.240 --> 0:24:16.520 sustain a constant body temperature, and do really powerful energy 0:24:16.920 --> 0:24:20.800 consuming things like run and fly and do these kind 0:24:20.880 --> 0:24:24.199 of things. If you have a very high metabolism, you 0:24:24.320 --> 0:24:27.679 have to go through these processes of making new cells 0:24:27.760 --> 0:24:31.600