SciShow Tangents - Proteins

Episode Date: July 28, 2020

What do proteins do? Heck, an easier question to answer would be 'what don't they do?" No, seriously... I think they do, like, everything. Follow us on Twitter @SciShowTangents, where we’ll tweet out topics for upcoming episodes and you can ask the science couch questions! While you're at it, check out the Tangents crew on Twitter: Stefan: @itsmestefanchin Ceri: @ceriley Sam: @slamschultz Hank: @hankgreenIf you want to learn more about any of our main topics, check out these links![Truth or Fail]Protein gamehttps://www.scientificamerican.com/article/victory-for-crowdsourced-biomolecule2/Protein musichttps://www.sciencedaily.com/releases/2019/06/190626125052.htmWhey fabrichttps://www.eurekalert.org/pub_releases/2017-01/ded-ssa012317.php[Fact Off]Prions in wine yeasthttps://phys.org/news/2014-08-prions-trigger-stuck-wine-fermentations.html#:~:text=Working%20through%20a%20prion%E2%80%94an,without%20altering%20the%20yeast's%20DNA.Spider silk in vaccineshttps://www.sciencedaily.com/releases/2018/06/180612185155.htmhttps://www.eurekalert.org/pub_releases/2018-06/udg-ank061218.phphttps://www.sciencedirect.com/science/article/pii/S0142961218302473?via%3Dihubhttp://news.mit.edu/2019/spider-silk-humidity-robotic-muscle-0301[Ask the Science Couch]Complete proteinshttps://goaskalice.columbia.edu/answered-questions/complete-and-incomplete-proteins-grains-and-vegetableshttps://medlineplus.gov/ency/article/002467.htmhttps://medlineplus.gov/ency/article/002222.htmhttps://www.eurekalert.org/pub_releases/2019-03/cfgr-utr031119.phphttps://academic.oup.com/jn/article/134/6/1558S/4688841[Butt One More Thing]Sonic hedgehog anorectal malformationhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC1850556/

Hello and welcome to SciShow Tangents, the lightly competitive knowledge showcase starring some of the geniuses that make the YouTube series SciShow happen. This week, as always, I'm joined by Stefan Chen. What's up? Stefan, what's your tagline? I'm a cabbage. Mm, classy. Sam Schultz is also here today.

Sam, what's your coffee order? My coffee order? Black. Well, gosh, black until recently. I started just drip. I don't drink. I only drink drip. I started putting cream and sugar in it.

Now I just do cream, though. Sugar seemed too ostentatious. Oh, ostentatious. Wow. That's a big word for the normal way to drink coffee. Sam, what's your tagline? Somebody get this freaking duck away from me. Oh, God.

Tell me about it. Sari's here as well. Hi, Sari Riley. Hello. Would you describe yourself more as classy or bougie? I would say neither. Is that a dichotomy? Is that a thing?

No, you could be both. That's the whole point of the song. Oh, I don't know this song. Oh, it's the TikTok song. I think I'm more ratchet than classy or bougie, probably. Oh, no. You're going to talk about something I don't know. What song is this? It's Megan Thee Stallie, probably. Oh, no. You're going to talk about something I don't know. What song is this?

It's Megan Thee Stallion, Savage. Oh, okay. It's real hot on TikTok. I at least know who that is. Good. I don't actually know who that is. I just am on TikTok a lot. Terry, what's your tagline?

Big Leaf Energy. And I'm Hank Green. My tagline is Banana Combos. That sounds really good. Every week here on SciShow Tangents, we get together to try to one-up a maze and delight each other with science facts. We play for glory, but we also keep score. So it's not really for glory. It's for the win, and I'm losing. We do everything we can to stay on topic, but judging by previous conversations, we won't be good at that. So if the rest of the team deems your tangent unworthy, we'll force you to give up

one of your sandbox. The good news is for me, I've given up so I can tangent as much as I want. Now, as always, we introduce this week's topic with the traditional science poem

this week from Sari. A workout trope, the protein obsession to grow your muscles into prized possessions, get swole, drink shakes, get strong, eat beans, load up your body with precious amines. But these little strings are in lots of things, folding and molding every offspring, from development proteins to photopsins

and cones in eggs, hair, and meat, hormones in our bones, and lignin in wood that helps it grow strong, but prions, I fear, make things go wrong. The real puzzle of proteins, both big and small, is that proteins need proteins to exist at all. Chaperonins help fold and proteases break down. But these protein makers and breakers aren't just around. They have to be made. And that's what confounds me when it comes to studying life.

It's basically just chance. I'm tired. Good night. me when it comes to studying life. It's basically just chance. I'm tired. Good night. So our topic for the today is proteins, everyone.

Proteins, the thing that makes us all up for the most part, certainly that make us all function. And I think that there's a fairly specific definition of a protein. I'd love to hear it. I have no idea. This is one of those episodes where I actually studied this in school, so I feel a great amount of pressure to get it correct because it's a chemistry-biology intersection. So proteins are also known as polypeptides because they are chains of amino acids bonded together. So they're chains of amino acids, which gives them like their primary structure, but then they have secondary and tertiary structures where they fold and twist and have internal bonding so that they form 3D structures. And protein folding is a huge

problem in the field of science. It just like feels magical in some ways. Like we can predict somewhat how proteins are going to fold, but not really. And their structure influences their function. So if they fold incorrectly or become unfolded, then it won't work like a protein should. So if we could predict it, we'd be able to stop some things from happening or like make other things happen? Is that why we want to even try to predict it? It'd be nice to be able to predict it because then if we were to want to create a shape, we could do that. If you want to create a protein to do something specific, then you could be like, oh, I know how this is going to fold up. Also, proteins can fold up in different ways. So like one protein can fold in multiple conformations.

fold up in different ways. So like one protein can fold in multiple conformations. And if you make it in a lab, it might fold very differently than if it makes itself or if it is made in your body by your body, by a ribosome. It's a big mess. And like the wild thing about proteins is how effective they are at their jobs and the creation of them to do the work that they do is way beyond kind of where we're at right now we're much better at sort of like finding proteins and like using them to do stuff than we are at creating proteins to do their remarkable work of creating stuff that we still cannot create like one of my things that i always go back to is like we still don't know how to make wood trees do it all day every day and they make so much wood and it is amazing like it's this amazingly useful thing we have no idea how to make wood and in fact cannot do that like to make proteins we co-opt the systems of other microorganisms so a lot of the time we stick a gene,

like we understand genetic material enough to like cut and paste and do things like that with it. But we stick a gene into bacteria and then we're like, you live your life and just generate a bunch of this protein so I can have it. Because we don't know how to just make that protein in a lab. It's so wild to me. It's like, well, you're gonna do the labor for us

because we just can't figure this puzzle out and it's much easier to just trick you into making it. The chemical systems that happen on earth are so far beyond the chemical systems that we use to create organic compounds. Actually in a lab, using organic chemistry rather than using biological systems to create stuff for us really makes me feel like we kind of suck at chemistry because our bodies are way better at chemistry than we are. So what's it mean? Does it come from proteus, the first something? Yeah. Where did protein come from? You're right, Sam. That's basically what comes, protose first, and then plusene,

which I did not look up the etymology of for some reason. Maybe fame. Word-forming element. That's it. It's just a part of a word. So, yeah. It's a word-forming element. We turned this thing into a word.

Yeah. It was like, it is the first thing. And I think in Greek times, it was just used generically because they didn't have a specific understanding of biology. There was just like, there is something that is essential to life and we're going to call it a proteus or something like that or a protos. And then in 1838, the Dutch chemist Gerhard Mulder used the term protein in his paper to refer to specific substances in animals. And then I think from there on, the scientific community started narrowing it down. It's like, okay, what exactly is a protein? What essential compound are we going to call a protein?

And then the rest is history. And now it is time for Truth or Fail. One of our panelists has prepared three science facts for our education and enjoyment, but only one of those facts is true. The other two are fakes. The rest of us have to figure out either by deduction or wild guess which is the true fact. And if we do, we get a sandbuck. If not, then Stefan will get the sandbuck because Stefan has brought the facts today. You can play along at home at twitter.com slash SciShow Tangents, but wait, wait until you've heard all of the facts before you vote. Stefan, what are our three facts?

These are three ways of exploring new protein structures. Number one, inspired by Minecraft, a team of researchers created a 3D block-based protein game in which players could manipulate proteins using amino acid blocks. And in 2012, players successfully re-engineered an enzyme that is used in the production of vitamin B6. And by adding 13 amino acids, they made the enzyme 18 times as active. That sounds like something people would do. Number two, a team translated protein sequences into music using a 20-tone musical scale that corresponds to the 20 standard amino acids that form proteins.

And a neural network trained on this protein music was then able to quickly generate whole new protein variations that they could create and test the properties of. That's fun. And just play them on a piano. And then number three, a team trying to create a new futuristic fabric that would be very elastic, but also stronger than some metals, studied whey protein, the stuff that you find in many protein powders, under x-ray light to discover how the proteins were combining to form fibers.

All right, so our three facts are, number one, there is a Minecraft-inspired game that was used to re-engineer an enzyme that's used in the production of vitamin B6, and they were able to make it 18 times as active. Or, number two, researchers translated protein sequences into music and trained a neural network on that music to generate new protein variations. Or number three, a team tried to create a strong elastic fabric out of whey protein. Explain this to me. They're using whey protein, which I know as a thing that I can digest because they put it in food and they turned it into something I can wear. You can wear food. My bad, of course.

So a bunch of steaks together. Got a shirt. Do they like re-engineer this somehow? There's like a process that involves a lot of pressure, I think, that forms the fibers. Are proteins the ones you can denature? Yep. They probably denature them. They probably did.

That's when you unfold them, basically. When you cook them up. It's the denaturing process. Yeah, like frying an egg. So then they get all clumpy with each other. Right. Number two, did the song sound good at all? Well, it is not familiar to listeners of Western music.

Let's put it that way. It would be a little bit all over the place because you just have 20 notes and like there's no, I don't know. It's not like any protein has to be next to any other protein like in a sequence or anything. Yeah. Well, I mean, so there are repeating patterns in proteins, but yeah, there's no particular reason why, like even like why we assign them

certain numbers. But you can make a song out of 20 notes. There's lots of songs so it's less than 20 notes. There's only really 12 notes. They just repeat. And I believe anybody

in Minecraft could do like literally anything in an infinite amount of free time. Yeah, that is the trick. If you can get your science inside of Minecraft, all the children will do it for you. Yeah. All right, all right.

I think I'm going to go with the weird milk clothes. I'm also going to go with milk clothes. Oh, gosh. We're going in on it. I think I'm going to go with the Minecraft one. going in on it oh i think i'm gonna go with the minecraft one i have infinite faith in minecraft players i also have a lot of faith in minecraft children but the correct answer is the protein music it's a sweep at this point hank i think you should just try to hit zero points by the end of the season.

I'm going down. I get ready to hear everything I know. So yeah, so they translated different aspects of the proteins into different aspects of music. And I think they called it the amino acid scale. I guess like the amino acids are physically vibrating at certain frequencies. And so they could translate that into the pitches and then transposed it to

within the human range of hearing. And then the secondary structure of the protein, which I think is, I mean, you could probably correct me, but I think has to do with how it's actually arranged in space, like in physical space, the shape of the proteins,

that information was encoded as the volume of the notes and the duration. So some of the researchers were saying they had listened to a bunch of this music and they were starting to be able to be like, oh, that sounds like an alpha helix or something. They could hear different physical structures. And as Sari was mentioning, protein structures are really complex and affect how proteins work. So they were trying to use music, something that humans are better at understanding naturally to help try to break down differences between the proteins and their variations and like protein families and stuff.

And they were saying the neural network seems to understand like the code or recipe of how proteins are designed, but they can't like open up the AI and see what's actually going on. So that, but, but it does seem to work. So there, there is a protein game. I think there is a protein game based on Minecraft, but I don't know anything about that one, but there's another like citizen science project called fold it where the players are trying to fold proteins in different ways. Um, and in 2012, they had the first crowdsourced redesign of a protein

and it was an enzyme used in Diels-Alder reactions. I don't know what that means, but it's apparently used in the production of various things, which includes vitamin B6. And the original creator of that enzyme was stuck on... He needed it to be more potent, but couldn't figure it out. And so the players of Foldit were able to make it 18 times more effective. The new futuristic fabric that would be very elastic but also strong is just silk. There's a team that's working towards a process that would allow them to artificially produce silk, because right now you just have to use silkworms. But silk is super elastic and super strong.

And so being able to produce it or mass produce it in the lab, I guess, would be useful. They took whey protein, or it's like a protein from cow's whey. And they knew that if they applied heat and acid to it, they could turn them into these little fibrils. And so I don't know if that counts as denaturing, but it changes the shape into like some kind of spaghetti. And then they found that different concentrations of the protein in their solution determined the properties of the fibrils.

So like different lengths and thicknesses and straightnesses. And they were surprised to find that it was the shorter and thinner ones that turned into a better fiber. They found that the shorter ones were more, turned into a better fiber. They found that the shorter ones were more like maintained or more random orientation and were more curved. And that just helped them lock together with each other more. So they'll like thicker, but straighter ones. It's like trying to hold a bunch of spaghetti together. Like there's nothing to

lock onto, I guess, but they were able to make five millimeters of silk. That was of medium quality. Now that they understand this whole process a little bit better, they're, they're able to make five millimeters of silk that was of medium quality now that they understand this whole process a little bit better they're they're gonna try to make better fibers but i think they're not using whey protein for that that was just for this part of the experiment to like figure out how it all works the music one sounded so fake i'm mad yeah i had also heard recently somebody who was like translating like markets into music. And so I thought you were just riffing off of that. Oh, like stock markets? Yeah.

Yes. I don't know what good that does except to like freak you out. Yeah. I listened to like the last six months and it was unpleasant. All right. Next up, we're going to take a short break then it'll be time for the fact off welcome back everybody sam buck totals hank and sam coming in with nothing Welcome back, everybody.

Sam Buck totals. Hank and Sam coming in with nothing. Sarah's got one for the poem. Stefan raked it all in with three points during Truth or Fail. And now it is time for the fact off, where Sam and I have each brought facts to present to the others in an attempt to blow their minds. Sarah and Stefan each have a Sam Buck to award to the fact that they like the most

and decide who's going to go first. We have a trivia question that is going to be read by someone to us. Me. So like we've been talking about, proteins can become thermally unstable and denature or unfold at temperatures outside of the range that cells live. For hyperthermophilic bacteria, though, that range is really high. So what is the highest temperature in Celsius

that hyperthermophilic bacteria have been observed to survive without becoming unstable? Now I gotta learn Celsius real quick. I think you know the important number in this situation. What do you mean? 100? Yeah. You know, there's the upper limit when water stops existing

is 100. I'm gonna go first, since I've given Sam a hint now. And I'll say, what? 99? Oh. I don't know why you would think that a hint would help me in any way. How about 120?

Wow. The answer is 122 degrees Celsius. No! Which is, by my calculations, 251.6 degrees Fahrenheit. My God, that was amazing. All right, Sam, you want to go first or you want me to? I think I want you to go first. Okay, I will. So we've also talked a little bit about prions during this podcast.

And we know what prion diseases are. And we know what prion diseases are, but just to explain, it's when a protein takes on a shape that is, you know, unlike the shape it's supposed to be. But then that protein in that conformation becomes infectious. So the prion can then bind to the other versions of the same protein, and then they will change to that new bad shape as well. And then they'll bind to more proteins, and then that will create more prions, and then it spreads so that the proteins that are supposed to be one conformation, it's like an infectious change in conformation. This is how mad cow disease works, a number of other diseases, but it is also sometimes responsible for messing up your wine. So yeast eats sugar, and when they do that, they produce alcohol. And when bacteria consume sugar, they produce acids like lactic acid. Winemakers want wine with alcohol, not with extra acid.

But sometimes yeast fermentation can get stuck stuck and instead bacteria come in and consume all the sugar and basically the wine isn't wine. It doesn't taste like wine. It does not taste good, even if you like the taste of wine, which I don't really, I don't quite get it, but that's neither here nor there. So like the yeast fermentation relies on this process called glucose repression. That's a process that blocks the yeast from consuming anything other than the sugar from the grapes. It keeps it focused on that sugar and moving fast, and it's especially strong in Saccharomyces cerevisiae, which is the yeast that we use in almost all brewing and baking. But scientists have found bacteria that can come in

during the winemaking process and send signals to the yeast that cause prions to replicate in the yeast membrane. And those prions block the glucose repression. And then they cause the yeast to start consuming other stuff besides sugar that slows down the fermentation. And it also opens up this glucose for the bacteria to consume. And so that basically spoils the wine. Now, that sounds like a very crafty thing for bacteria to be able to do. And you'd think maybe, like, wouldn't yeast have figured out a way around this? But it turns out that though prions are usually bad, in this case, this might actually be

something that yeast evolved to benefit themselves so the prion switching in their membrane might be a way for the organisms to like hedge their bets and kind of be able to like switch back and forth between two different conditions to let them adapt really quickly when food sources change or like suddenly there's bacteria in the room so that they might like broaden their variety of diets and and like it's able to do that by having a change in its membrane that is is caused by bacteria but not something that's like permanent like a genetic adaptation so in this case both the yeast and the bacteria can benefit from what they call stuck fermentation. As the yeast start metabolizing less sugar, the wine becomes more habitable to the bacteria and the yeast can start consuming

stuff from more carbon sources. That's great for them. It's bad for us and winemakers, which is why they add sulfur dioxide early in the process often because that kills off the bacteria and prevents stuck fermentation. Oh, they're killing their little friends. That's right. So that they don't give them a weird membrane-bound prion disease that's not actually a disease, it's actually good. Okay, so you say conformation, is that just like configuration? Is that like a similar? It's like the shape that the protein takes. So a protein can take several different different shapes and there's all kinds of things that can change protein confirmation so whenever you hear about binding something binding to a protein usually that means that that binding changes

the confirmation the protein and in the case of like uh you know a taste receptor in your mouth like sugar binds to the taste receptor protein that changed the confirmation and that like opens up some kind of signal into your neural pathways that then gets interpreted as sweet by your brain so can a protein fold into different folds in the course of its protein lifetime yeah that's what changing confirmation is and sometimes it's like helpful to the protein's function. Like it needs to change shape a little bit in order to do what it does, whether it's convey a signal or help break down a compound or have something bind to it. And sometimes it's unhelpful where the change induced in it, like with prion diseases, breaks it so that it can't do anything that it was supposed to do.

The shape is weird instead of useful in some way. And then it can tell its friends to turn into that shape too. Right. So basically that shape binds two other proteins of the same type and causes those proteins to change into that new bad shape.

What the hell? The proteins give each other hugs and then they end that new bad shape. Yeah. What the hell? Yeah. The proteins like give each other hugs and then they like end up the same shape. There's a lot of stuff going on inside of this, huh? Well, hopefully that's not happening inside of you. Though there is now like thought that this kind of like, prion is just like a name for a protein that self-perpetuates its confirmation.

Okay. And so it may be like, as in this case, that there are some prions that actually confer benefit, but we're really used to thinking of them as diseases. So none of this helps us make better wine, though? Well, knowing this helps us understand why bad wine happens, though it doesn't really help us make bad wine

because even before we understood why it happens, we knew how to prevent it, which was to kill the bacteria. We just weren't sure like why the bacteria were causing this change in the yeast. It could potentially help us make extremely nasty wine for like prank purposes. Yeah.

Okay, my turn. Like we've probably talked about a million times before and like I had to ask Sari a lot of million questions about today while I was writing this, when you get a vaccination, you are being injected with proteins isolated from a disease-causing molecule that activates your immune system and basically helps to like train it to fight the disease without actually having to go through having the disease. Is that right? Yeah. Okay. disease without actually having to go through having the disease. Is that right? So the concept

behind a vaccine for a disease or a bacteria seems pretty straightforward to a dumb guy like me, but researchers have long been looking into a vaccine for cancer, which is a disease that is made up of your own body cells, which is trickier. So this is where I'm going to get out of my depth even more. Part of your immune system is made up of T and B cells, which are types of white blood cells that attack diseases in different ways. So B cells make antibodies that neutralize viruses and bacterias. And then there are certain T cells that just straight up kill infected cells. Many vaccines trigger B cells, but T cells are the ones that kill cancer. So a cancer vaccine would need to trigger those killer T cells using proteins from the cancers. But the problem is

those proteins aren't durable enough to last in the body long enough to activate T cells, which are already harder to activate than B cells are. So cancer vaccines are tough to make and they don't work very often because it will like disintegrate before it even gets where it's supposed to go. Luckily, we have an unlikely ally in the search for a cancer vaccine. And that ally is my greatest foe, the spider. So spider webs are made of strands of incredibly tough and resistant proteins that thanks to the miracles of modern science, we can engineer in a lab in any kind of microform that we want to. So in 2018, researchers in Germany fused these T-cell activating proteins like cancer vaccines that they're studying for cancer vaccines into microscopic shells

made of spider web molecules and then injected them into mice and found that not only were the shells tough enough to convey the proteins through the body safely, they quote, considerably increased T lymphocyte or T cell immune responses. But how considerably that was, was locked behind a paywall. So I couldn't quite figure that out. So that added spider web toughness also potentially means that we can make more resilient vaccines of all types that can survive in temperatures of up to 212 Fahrenheit. I don't know how much Celsius that is, meaning that they could be transported far more easily than vaccines we have now that basically need to either be frozen or refrigerated all the time. So in addition to that, artificial spider web protein strands are being researched for use as artificial muscle fibers and a substrate on which to grow various human tissues like

heart tissue and stuff like that. So thanks to spiders, I guess. Thanks spiders, I guess. Pretty soon we'll be all spider. All of our organ, animal, and vaccines. I don't want to be any spider. I'm in this finished basement. I'm so scared all the time

that a spider's going to sneak up on me. Do you want to live forever? Because if you want to live forever, you're going to have to be part spider. That's the rules. Oh no. That's such a cursed trade off. I don't know.

Maybe the first time you let, you just like succumb and you say, okay, I'm going to be part spider. Maybe that's the moment when suddenly you see your spider brothers as the siblings they are. As a part of your family in that we are all related to the last universal common ancestor. And basically are all the same organism. All right, you guys. So now, Sari, Stefan,

you have to vote for the one that you like the most. Was it mine with yeast prions putting a pause on winemaking but actually helping the yeast all along? Or Sam with spiderweb proteins maybe able to help cancer vaccines last long enough in the human body to be effective and also potentially long enough to get to places where they can be used without refrigeration.

Three, two, one. Sam? All right, I got one point, you guys. All right, everybody, it's time for Ask the Science Couch. We've got a listener question for our couch of finely honed scientific minds. It's from at Topato Chipsis. What is a complete protein? Are there

incomplete proteins? Gosh, that's an interesting question. Do you know anything about it, Hank? Well, I don't know what if a complete protein is a thing, I don't know about it. There are certainly incomplete proteins. You can make a protein that's not all the way done. I think it's not like

a single protein. I think it's not like a single protein. I think it's just like a descriptor for foods that contain all the proteins you need or combinations of foods that contain all the proteins. Okay, it's a nutritional category. Okay. Yeah, and this is also where my weakness comes in where I'm like, I also initially thought the question was asking about like protein

as a singular thing, but this is a nutrition question in disguise, which means Stefan's going to be good at it. Well, is it about whether the protein in a plant or animal contains all of the proteins we need? All of the amino acids we need. That's what I meant, yeah. Like Stefan was saying with his truth or fail, there are 20 standard amino acids involved in protein formation. There's one extra selenocysteine that's kind of weird and it can like be produced in other biological ways, but it's not like existent in food that we eat. I think it's a mystery.

I'm not going to address it too much. Selenocysteine exists. So don't at me about that. Mostly that is what I wanted to get out. But there are different categories of amino acids. There are essential amino acids, which can't be made by the human body. There are conditionally essential amino acids, which can sometimes be, but you can also be deficient in them. So like, for example, babies can be deficient in arginine, which causes a variety

of health problems. So like their bodies might not make enough and we have to supplement with it. And then there are non-essential, which your body just makes them out of other compounds inside or by breaking things down. And so a complete protein in nutrition sense means it's just a food that like supplies you with all essential amino acids. And I think there are some foods that have it, but then there's some combinations of foods. So that's where you get like peanut butter and toast or rice and beans or other things that I read on the website. I don't know. Ezekiel bread. This is where Stefan might know more. Hummus and pita. Quinoa, I think is complete.

Most meats and eggs are complete proteins, which is why you have to think about the combinations more if you're a vegetarian or vegan. I can't believe I'd never heard of this. If you want to ask the Science Couch your question, follow us on Twitter at SciShowTangents, where we'll tweet out topics from upcoming episodes every week. Thank you to

at Velociraptorial, at Vinay Verma, and everybody else who tweeted us your questions for this episode. Sambuck final scores. Everybody's got one Sambuck, except for Stefan, who's got three, which means that Stefan has pulled substantially

into the lead with 58 Sam books. Sari and Sam are 55 and 54, and I just want to not talk about it. If you like this show and you want to help us out, it's really easy to do that. First, you can leave us a review wherever you listen. That helps us know what you like about the show, and also it just feels good to read them.

So thank you for the people who have sent those in. Second, you can tweet out your favorite moment from the episode, and finally, if you want to show your love for SciShow Tangents, just tell people about us! Thank you for joining us. I've been Hank Green. I've been Sari Reilly. I've been Stefan Chin. And I've been Sam Schultz. SciShow Tangents is a co-production of

Complexly and the wonderful team at WNYC Studios. It's created by all of us and produced by Caitlin Hoffmeister and Sam Schultz, who edits a lot of these episodes along with Hiroko Matsushima. Our social media organizer is Paola Garcia Prieto. Our editorial assistant is Deboki Chakravarti. And our sound design is by Joseph Tunamedish.

Of course, we couldn't make any of this without our patrons on Patreon, so thank you so much to them. And remember, the mind is not a vessel to be filled, but a fire to be lighted but one more thing there's this protein called Sonic Hedgehog that doesn't have anything to do with going fast, but it does have to do with body layout during development.

And in fact, if it's mutated, that can cause anal rectal malformations, aka butt development problems, and lots of different animals, including mammals. You really need the butt. You do. It's true. It's one of the main things you need.