S1E7 - Cytosis (Cell Biology)

Today we cover Cytosis, a worker-placement game about cell biology from Genius Games. This is one of our all-time high scorers, with both excellent science and excellent gameplay. Join us for a tour de cell as we go through the nucleus, endoplasmic reticulum, Golgi, mitochondria, and cell membrane, plus gush over how cute kinesins are and argue about whether bacteria have organelles.
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#BoardGames #Science #CellBiology #GeniusGames #Cytosis #Protein #RNA #DNA #Hormones
Timestamps:
00:51 - Protein sequencing
03:54 - Intro to Genius Games
06:50 - Intro to Cytosis
12:48 - Cells & their parts
16:06 - RNA & ribosomes
20:22 - Endoplasmic reticulum, Golgi, & hormones
24:48 - Mitochondria & glucose transport
27:11 - Learning from the game
28:40 - Bacteria
30:58 - Inconsequential nitpicks
36:11 - Final grades

Links:
Official Website (Genius Games)
Reverse Translation (preprint)
Video of John Conveyou
Organelles of a Euakaryotic cell (Wikipedia)
Kinsesin motor proteins

Full Transcript:
Jason  0:00  
Music. Hello and welcome to the gaming with science podcast where we talk about the science behind some of your favorite games.
Brian  0:12  
Today, we're going to discuss Cytosis by Genius Games. Hey, I'm Brian.
Jason  0:21  
This is Jason.
Brian  0:23  
Welcome back to Gaming with Science. Today, we're going to talk about Cytosis, a cell biology game. It was a game designed by John Coveyou by Genius Games. I don't know why it's taken us this long to do a Genius Games game, considering they are specialists in hard science games, and they seem to share the exact same core values as gaming with Science. I know this is our first. I'm sure it won't be our last. But anyway, before we get into that game, Jason, do you have anything for us to banter about?
Jason  0:51  
Well, I like the science topics, and you actually pointed me out to one that's related to this, which is a preprint. So you've got publications in final journals, but you also these things called Preprints, which is where you post your paper up before it's been peer-reviewed, so you can get the results out. You can kind of stake a claim to it. But according to their preprint, they've developed a way to do not quite reverse translation, but something similar. So we're going to talk about this more later today, where translation is where you take the genetic information from a cell and turn it into protein, and it's generally a one way street. You can't go back, but this group has developed a method to, not so much go backwards, but at least to take the proteins apart in such a way that it's encoded in DNA that they can then sequence and get back out. And this is really cool, because we're really good, like we as a field, science is very good at sequencing DNA right now. DNA sequencing in some form, has been around for 40, 50, years, but high throughput sequencing has been around for at least 20 years now. Ee're very, very good at it now. In fact, we're astonishingly good at how much DNA we can sequence. We suck at sequencing proteins. It can be done. It's like, don't get me wrong, there are methods to do it, but compared to what we can do with DNA, it's slow, it's expensive, it's hard, and I don't know that this method really solves all of those problems, but it potentially gets rid of some of them. And if we can find a way of turning proteins, protein information, into DNA information, and just hooking into the existing DNA sequencing infrastructure, that could open up whole new ways of looking at biology, looking at things, because most of the time, it's the protein that matters. We look at the DNA because the DNA is easy, but most of that, one way or another, ends up in a protein, either directly or by changing which proteins are around. And so being able to look at the proteins more directly gives us a lot more information about diseases, about things that in plant science we care about, like crop production or disease resistance. It's like there's a really cool thing that could open up there. And so even if this group doesn't work out, I hope someone manages to, like, build off of this and make it work. 
Brian  3:00  
This is the first time I've seen a preprint, and be like, someone's going to get a Nobel Prize for this idea. Maybe not this group, but somebody's going to get this to work, and somebody's going to have a Nobel Prize for this. I mean, the whole idea about DNA. Why are we so good at doing DNA? Because DNA is set up to make copies of itself, right? You can take a very small amount of nucleic acid and using a process called the polymerase chain reaction, generate massive amounts of DNA. You can go from one molecule to a billion in a couple of hours. So you could start from a low amount of material and work up to a huge amount of material. But proteins don't do that right? It's one direction. So the only way to read the proteins out is you just make more and more and more sensitive instruments. It's neat to see something that could change the field so drastically in such a short period of time. 
Jason  3:45  
Yeah, so will this one pan out? Don't know, but it's really cool in the meantime. 
Brian  3:49  
Yeah, for sure. All right, so do you want to talk about cytosis? 
Jason  3:52  
Yeah, let's dig into this.
Brian  3:54  
You know, when I do these, I usually try to do a little bit on the designer of the games. So again, the designer of such. Well, what is cytosis? Cytosis? What does it actually mean? Cytosis isn't actually a word that you typically see on its own. It's the Greek root that means cell. So cytosis would just mean "of the cell," so exocytosis "out of the cell." Anyway. You'll see cytosis a lot, of a lot of places, but that's not typically a word you'll find out on its own. But this is a game about cells. I mean, that is the the proxy of this. It's cytosis, a cell biology game. So the designer, John Conveyou, he seems like a really interesting guy. In fact, in the show notes, I'm going to point to an interview that he did that kind of gives a little bit of his history in his past and like, what brought him to this place. But the short version of it is, is that he has a master's degree in engineering, that he was a science teacher for a while, teaching biology, teaching chemistry, teaching all these core things. Had an engineering position and left it to found Genius Games, is he a CEO and founder, and is as near as I can tell, the lead designer on pretty much every one of their products. They may have co designers, but his name is on basically every one of them, and a lot of these were his ideas. He  also has these games that are like partner games. So he has chemistry games, Ionic and Covalent, that are a pair of games that talk about ionic bonds and covalent bonds. He's been working on a series of games that will go from transcription, making a RNA to making a peptide to and again, all the way building up, just like cytosis. Anyway. So what is Genius Games? Genius Games is this company that again, like I'm surprised that we haven't dealt with them yet. They have a great tagline: "credible science, incredible games." They do have a mission statement. And if I was to boil it down, I'm going to paraphrase a little bit, basically, they just believe in the power of scientific literacy to solve societal problems, and they also believe in the democratization of science literacy, and that games are a good way to do that. So they make games that are hard science themes, games where the science and the science concepts are in the center of the game. You know, if we consider wingspan our A, I mean, hopefully a good Genius Games should be like an A+ in terms of like, that's the whole point, is learning the science as you play the game. 
Jason  6:01  
You've complained in the past about games where the science is there, but not, like, super integrated into the game. And it sounds like the whole modus operandi of this company is that, no, the science is going to be at the center, and we're going to have a partnership between the science and the game. So it's not just painted on top of it. 
Brian  6:17  
Education games has kind of a dirty word in the gaming industry. Education Games is a way of, like, just putting something on your games that's like, well, is the game fun to play? Well, no, but it's educational. So that is also counter to their design principles. Here, the game needs to be fun and awesome to play. And also, by the way, you're going to learn a lot of good science at the same time. That's a lot more than we would usually talk about the creator and the company, but it, this company needed a little bit of time to talk about. And like I said, there are definitely other Genius Games, games from this company that we're going to talk about in the future. In fact, we have some planned already for season two. But what is cytosis itself? The game is a worker placement game. If you've ever seen a model of a cell, which I think we all have at some point, you lay this out, and you have the player mat that looks like a diagram of a generic human cell. We've all probably had to take a test where you had to label the little parts of the cell. It's like, oh, where's the nucleus? Where's the endoplasmic reticulum? Well, it's that in game form. So you've got this mat in front of you with all the, not all, but a lot of the little organelles. And at each of these there's going to be a little place where you do worker placement, where you're going to do different actions. You're going to have four different types of research cubes, black for mRNA, red for protein, yellow for lipids, and green for carbohydrates. I think maybe there's a little bit of a color choice there. I mean, I imagine red for protein kind of makes sense. We think about like meat. Fats are often yellow. I don't know why carbohydrates are green, but they are.
Jason  7:44  
They come from plants?
Brian  7:45  
Oh yeah, that makes sense to me. Why do you think mRNA is black? 
Jason  7:49  
That I don't know. Maybe because the nucleus is usually dark and that's where it's generated? 
Brian  7:53  
That seems as good a reason as any. You also have these little tokens that are ATP. They're kind of shaped like a little ATP molecule. I don't know why those aren't a token or something. Probably just to distinguish them from the other cellular resources, which functions as the sort of currency in the game, just like it is in the cell, which I'm sorry I'm kind of jumping around. We're going to come back and talk about the science stuff more. So if this is unfamiliar, don't worry. We're going to come back and talk about it. In addition to that, you have cards at the top that are sort of like public goal cards that you can claim. You get bonus points around the cell. You got your point tracker. I would say that ultimately worker placement games kind of all have a relatively common language in terms of how this stuff works there. If you're familiar with one worker placement game, you kind of get the idea you can see how this is going to work.
Jason  8:39  
And in case anyone isn't, the basic idea is you have a set number of actions every turn, and you have something to represent those. And so you, you put your little worker, which could be a meeple of some sort, usually. In this case, they're little beakers, and you just, you put it on a spot, and you say, Okay, I'm going to do this action. And usually there's only so many spots to do that action. So if I claim the ability to make mRNA, then Brian cannot also claim that one, or at least he doesn't get as good a one as I did. So there's a strategy in terms of you can't just pick what's best all the time, because if someone else blocks your path, then suddenly you're out and you have to wait until next turn to do it. So that's some of the tension of it. There's finite places to go, and everyone's competing for whatever they need.
Brian  9:21  
There's a best spot and a second best spot. And then if you're playing with a lot of people, it's like, well, I just can't do that this turn, right? You'll also have a deck of event cards that you play in between rounds that may do things like, oh, there's going to be extra ATP available this turn. Or some of the cards are bad. If you've been hoarding your resource cubes now you've experienced toxicity, so you'll suffer from that. And then the other type of card is a cell component card. These are the things that you're going to be building in your cell and that are going to be earning you points. Other than that, the each individual player, like Jason said, has different colors of little flasks that, in this case, are our little meeples, let us do our actions, and as well as some little vesicles. Some little circle disks that you'll use to build some of your cell components. So that is what the game looks like. So as you play the game, you will take turns placing your little flasks to choose what you want to do. It'll allow you to collect the different resources, protein, mRNA and you're trying to build these little cell components that you'll then also have to pay an energy costs to score points, which they call health points. Which I don't know, what would be better than that? Homeostasis points or something? I'll have my little nitpick session at the end of the game. I think I do like to have my little nit picks. I think Jason's more forgiving than I am. But, I mean, I don't have a problem with this game at all. It's a great game, but there's a few little things always that are, yeah, maybe this could be a little different. At the end of each round, you'll flip over an event card that will change the cell in some way, add new resources or toxicity, and that's it. You just go until all of the event cards are used up, and then you count up how many points you have. Is that a fair summary?
Jason  10:55  
There's a few little surprises in terms of points at the end because of the bonus cards and everything. But mostly  it's pretty straightforward. You, you buy your little goal cards that, that are your little cell component cards, so you can build them, and you can score points off of them, and there's a few interactions. I wouldn't say it's a linear game, but there, it's very clear what you're trying to do. You're trying to build things in such a way to get more points than your opponents. 
Brian  11:15  
Do you worry that the reason it feels linear to us is because these are familiar concepts?
Jason  11:20  
No, I don't think so. I think, I mean, the game is linear in that you're, you have this chain of resources you have to move down in order to make it happen. And I don't mean that as a complaint about it, where saying, Oh no, it's like you want lots of things. No, it's, it's more just that the goals are very clear. It's not like there's some hidden way where once you've played this five or six time, you suddenly realize, like, Oh, this is the secret way to actually get lots of points out. Which I have seen some games do that, where the things that seem obvious at first are actually not the best choices. This is not one of them. Like the goals cards are pretty clear. There may be some nuances of interaction that open up a bit more complexity as you, as you mature and you get good at it, but mostly like you open this up to a new player, you see some basic rules. They'll know what they're supposed to do in order to try to win.
Brian  12:05  
Particularly if you've played work replacement games before, right? Like, if you're in the hobby, this is gonna, you'll get this immediately. And it's got good board design to kind of lead you through it, like most modern games do, right? You're not having to memorize everything. It's right there on the board. 
Jason  12:20  
Yes
Brian  12:20  
Let's talk about the science here a little bit and like, how is the game representing the science? So I gotta say, we've had games that have done this before, but at Genius Games, they've done all my work for me. There is a four page pamphlet included with cytosis called "cytosis, the science behind the game," that breaks down the science and how the game represents the science, which usually is most of the work that I have, that we have to do when we're doing planning out an episode of Gaming with Science.
Jason  12:45  
Well, then the big question is, do they cite their sources?
Brian  12:48  
They do not cite their sources, but they do provide, but they do provide a list of all of the people that provided their sources. They crowdsource the science of this game, but they don't have a references cited list. That's true. I think at this point, the only one where we've said, where they were explicit about the sources, was wingspan. Let me, let me think about how the best way. So, okay, what is a cell? The cell is the basic unit of life, and all life is made of cells. In fact, most life is unicellular. Is just a single cell. But any living thing that you can see from you to every plant to your pets, is made up of cells, individual cells working together and coordinating to build this larger body. So and all cells have and have certain things in common. They all have a membrane that is comprised of lipids, a lipid bilayer, um, kind of like a soap bubble with two walls. Again, lipids are one of the resources in the game. I'm kind of going to be bouncing back and forth between the science and how the game represents it, because it just, it's so intrinsic. It just makes sense to do that.
Jason  13:50  
 And lipid is the the fancy science word for a fat or an oil or something.
Brian  13:54  
Fat, oil. Uh, let's see. So and then every cell is going to store its genetic information in DNA. Every cell is going to have proteins that are actually doing most of the work, providing most of the structure, and then every cell uses the same way of translating DNA, using RNA as an intermediate, into those proteins. That is every cell, and every cell basically uses the exact same code. There are so few exceptions to that rule that, like we make a very specific point about them when something is different. So you're going to notice I haven't talked about carbohydrates, which is the other thing that provides the energy for the cell. So these all make up the macromolecules we've got mRNA, protein, lipids, carbohydrates.
Jason  14:35  
And again, science term: "macro molecule" just means big molecule, because cells have big molecules, which are these very complicated things that are joined together, especially like the proteins and the, and the nucleic acids, like DNA and RNA, yeah, as opposed to simple molecules, which are small things. Water is one. Individual sugars are not macromolecules, but if you start joining them together into long things like starch, then they become macro molecules, because you start joining these small units together into much larger ones. 
Brian  15:02  
Yeah, I think, like, you can find small individual compounds, like in lots of different contexts, but then to find macromolecules, those are pretty much you're going to find those in cells or made by living cells. Like you can find little individual molecules inside of meteorites, but you're not going to find macromolecules like giant proteins, strains of DNA. In cytosis, we're playing as a human cell. What kind of cell? I don't know, some kind of generic human cell, but you can take all cells and you can split them into two big camps. There are eukaryotic cells, that's like our cells, that is a cell with a nucleus, that is a cell where the DNA is stored in a separate little compartment within the cell. That's the defining characteristic. So fungi, plants, humans and other animals, we are all eukaryotes. We all have these big, complicated cells with nuclei, and then in that they have other little compartments called organelles scattered around the cell that do different jobs. Usually those are also bound up in their own sort of separate little membrane bound compartment. And cytosis is kind of giving us a tour through the cell and how the cell works, right? I think I am also going to do that basic tour, and let's talk about the different things in the game. So again, I already mentioned DNA, where all the genetic information is stored. In a eukaryotic cell that is inside the nucleus. So if we want to express one of those genes from the DNA, we will turn a small portion of that DNA and copy it into a strand of mRNA messenger RNA. It's a single stranded RNA copy of the gene. How does the game represent that? In our nucleus is where we're going to get our RNA. That's one of the first steps, right? So one of your action, you place your action marker there, you can get some mRNA.
Jason  16:41  
Yeah, and this is the act of getting the information out of it. Think of a DNA as like, it's the long term storage of information in the cell, and it protects it. Your cells don't want to be accessing the DNA more than they have to, because every time you do, you open up the chance of getting damage. And if you damage your DNA, well, that damage gets copied, it gets saved. And basically you increase the chance that things are going to break down the line. So they don't actually want to access DNA much. So they will access it just a little bit to make an mRNA copy. This is like going to your big, fancy encyclopedia and just running off a quick photocopy of a few pages that you need access to. Then you put the encyclopedia back. You can take the pages out, you can mark them up, you can draw them on. You can put them through the shredder. Doesn't matter, because the original copy is still fine.
Brian  17:26  
It's funny how we keep having to update our analogies for these things too, because when was last time you made a photocopy of something?
Jason  17:32  
Okay, point
Brian  17:35  
But the principle is, is good and the principle is still there. DNA gets a lot of credit. We spend a lot of time talking about DNA, but the funny thing about DNA is DNA really does almost nothing, right? DNA is just the repository of information. The work is done by typically, by proteins, by enzymes that are doing the chemical react, doing most of the things in the cell are done by proteins. So the information stored in DNA, we got to turn it into proteins. That RNA copy carries the information for each protein. So we got to take that and then we got to load it onto another incredibly cool RNA molecule called a ribosome that can take that like an assembly line and read off the message in the RNA and convert that into a sequence of amino acids, the little, tiny bits and pieces, the 20 letter alphabet that makes up all the proteins in the cell.
Jason  18:26  
And this is so incredible. So this is like the core of life as we understand it, really, is this change going from nucleic acid to protein, going from RNA to protein. It is ancient. It is the thing that we use to basically tie all life on the planet together. As far as people can tell, it's thought that it basically predates DNA. So there's this thing called the RNA world hypothesis, because people are trying to figure out, How did life get started? Life is such a complicated, Rube-Goldberg contraption that it's like everything depends on everything else. How on earth could we have something simple enough to get going when we've just got a chemical soup going around? And the answer to that is still not known, but one hypothesis is that we once had a world of much simpler, of short RNAs and short peptides, small proteins working together, and the ribosome is one of the last and most robust artifacts from that time of turning RNA into protein. It's a ribozyme. It is an RNA enzyme, like the RNA does the work, which is really cool, because RNA usually doesn't do chemistry. It usually just stores information.
Brian  19:30  
Yeah, it is. It is the RNA is doing all the work. The proteins are there just to, you know, kind of provide support.
Jason  19:36  
It's a great big ball of RNA that has a few proteins stuck on the outside for decoration, but it is an RNA molecule. It is not a protein molecule. The protein is basically just providing stability. 
Brian  19:47  
So it's funny, we say DNA gets a lot of credit. Nobody pays attention to proteins. No, really, nobody pays attention to RNA. RNA is like the forgotten molecule. 
Jason  19:56  
Yes, I know my PhD work was in an RNA chemistry lab, and so we thought that all the time. And there's some really cool stuff that RNA can do that is probably outside the scope of this, this particular episode. But yes, RNA is the plants of the molecular biology. It's like, it just doesn't get all that much credit. People pay attention to the proteins and the DNA, and RNA just kind of overlooked.
Brian  20:18  
So, so we all have RNA blindness, is what you're saying?
Jason  20:21  
A lot, Yeah.
Brian  20:22  
Anyway, where were we? We got to turn our RNA into a protein, and the ribosomes are how we do that. So in Cytosis, you have two different places where you can do that. You've got our free ribosomes. These are floating in the cytosol, that liquidy, whatever that is full of all the stuff inside the cell, the inside bit, the goop. The free ribosome is where the cell is going to be making most of the proteins that the cell itself will use. But you've got another place that you're making proteins, and that is the rough endoplasmic reticulum. Oh, I really should have looked up the origin of these names. Do you know the origin of endoplasmic reticulum?
Jason  20:57  
So let's pick it apart. "Endoplasmic", so inside the plasm. So inside the cell. "Reticulum", reticulated is all sorts like folds and, yeah, complicated. So it's probably the really complicated folded thing inside the cell. 
Brian  21:11  
Yeah. So it's basically just totally based on the observation of what the shape is.
Jason  21:16  
And it has rough persons and smooth, rough has all these little dots on it. Smooth does not.
Brian  21:21  
And the rough one actually is rough, now we know, because it is studded with ribosomes. It is coated with the ribosomes. So the mRNA that is going to go into the endoplasmic reticulum will do so by accessing those ribosomes, and it gets stuck. The protein is stuck into the endoplasmic reticulum itself. So this is where all of the proteins that are going to get shipped outside of the cell will have to go or the proteins that are going to stay in the plasma membrane have to go into the endoplasmic reticulum first. Let's keep moving down this protein assembly line. So the next thing we're going to have is the Golgi apparatus. Do you know what the origin of that is? Because I also didn't look that up.
Jason  21:58  
I assume it's Mr. Golgi. That's all I've got.
Brian  22:00  
Probably Doctor Golgi
Jason  22:02  
Yes, probably Doctor Golgi.
Brian  22:05  
So our little proteins that are now in the endoplasmic reticulum will kind of get blebbed off in these little vesicles and then sent off to the Golgi apparatus, which is, again, just this kind of like, like hamburger stack of little membrane things. And this is a processing and shipping center. It's going to say, Oh, this protein needs to go here. This protein needs to go here. It's also a place where proteins can be modified. So a protein is made up of 20 amino acids, but sometimes you have to put some other bits on it, right. For instance, if it's going to be outside the cell and survive, sometimes you want to put some like sugar armor on it, basically to protect it. Carbohydrates, glycan, sugar. These are all similar terms. A lot of proteins that are going to stay outside the cell, you'll want to kind of decorate them. So you'll want to stick a carbohydrate on that. So in Cytosis, this is where, hey, you got to stick a, you got to add your carbohydrate to your little thing, showing that you're assembling this glycoprotein. 
Jason  22:57  
Oh, and probably the place that our listeners are most familiar with this is going to be the blood type. So the ABO blood types, or the positive, negative Rh factor, pretty sure those are protein modifications that are hooked onto the outside of the red blood cells. 
Brian  23:11  
And then at that point, once that protein is all done, it's been through the ER, it's been through the Golgi. Now we're going to ship it out of the cell, so it'll go through a process called, here we go, exocytosis. So there's our cytosis there. In the game, this is when you would collect your points, you actually have to pay your energy costs. In Cytosis, you play that energy cost when you're done, obviously, in a real cell, you're paying energy all the time. You can have a couple different things. You can create hormones that are used for cell-cell communication. This is why it's obviously a human cell, because they have to talk to each other, and hormones are how they do that.
Jason  23:42  
This'd be something like insulin. 
Brian  23:44  
Exactly. You can make receptors, which are the things that basically bind to and say, Hey, there's a hormone here. And will do signaling. Those are typically going to stay in the cell wall, and that's everything that is going to go out through the endoplasmic reticulum. Is two different types of receptor and the protein hormones.
Jason  24:00  
There's the steroid hormones, the fat based ones that get exported, right?
Brian  24:04  
Yes, there are so, and that's where we go back to, so we got the rough ER, so we also have smooth ER, what the heck is that? Smooth ER is where the cell makes its lipids and it will also make steroid hormones, which the fact that this cell is making so many hormones, I think, gives us some clue about what kind of cell this is. I'm pretty sure it's an endocrine cell for making all these different types of hormones. Your endocrine system produces all the hormones that your body uses to regulate all these cell functions. As you can imagine as a giant metropolis of cells, getting all those cells to talk to each other and coordinate is not necessarily easy. Hormones are one of the ways that your body does that. So the smooth ER is going to be make lipids, or lipid hormones. This is where you get your lipid resources. Testosterone is a steroid hormone, I believe.
Jason  24:45  
Yeah. The sex hormones are steroid hormones.
Brian  24:47  
Yeah. And those are going to start in this, in the smooth ER, go to the Golgi, and then get shipped out as well. Other than that, we have a couple other things that we haven't talked about. We have the mitochondria, which is very cool, the mitochondria, used to be a bacteria, that is the best way to put it.
Jason  25:03  
Probably best....Let's start with where it's at. So the mitochondria is called the powerhouse of the cell. It's what takes the food you take in, especially the sugars and such, and turns it into energy. That ATP molecule that is the energy currency of the game and the energy currency of the cell. 
Brian  25:17  
How do we know that it used to be a bacteria? It has its own DNA. It has its own tiny genome. It has its own ribosomes, and those ribosomes are the same shape and size as bacterial ribosomes. The genome itself is circular, like a bacterial genome. The "endosymbiosis hypothesis" is that this was a bacteria that was captured by some ancient precursor of eukaryotic cells and sort of domesticated into an organelle. They even have their own replication period. An individual cell can have hundreds of mitochondria in it. I think, for instance, muscle cells that need a lot of energy can have hundreds and hundreds of mitochondria inside of them. And the last little bit where we haven't really dealt with yet is the glucose transporter. So now we're at the plasma membrane. It's right. The plasma membrane defines the inside and the inside and the outside of the cell, which is great. You need that right? You need to keep what's in in. You need to keep what's out out, but you do need to move things back and forth. So in a process that typically costs energy, you have a whole series of specialized transporters on the outside of the cell that will take things in, like, for instance, glucose or other types of carbohydrates. Again, this is very simplified in cytosis, as it would be in any cell diagram. But here you pay a little bit of energy, and you get to bring in glucose. Now that actually couples very nicely with the mitochondria, because if you take one of your carbohydrate green cubes, you can burn it at the mitochondria, and you get, like, a massive influx of ATP. In the game it's six. In real life, it would be like 32 for one glucose molecule. 
Jason  26:46  
But it does nicely play up the fact that burning glucose in the mitochondria aerobically so with oxygen present gets you a huge amount of ATP. It's also possible to do it anaerobically without oxygen, and that gets you much less, which is maybe what those other spots are representing,
Brian  27:05  
I would assume. I mean, I'm not sure. Again, I think to a certain degree, some of this is just like game balance issues, right? 
Jason  27:11  
As you said, genius games wants the science to be central while making fun games. And how they made it so the way you do all of these components mirrors the way biology actually does it. You have to start by making your RNA. When you're making your little things to export out of the cell, you actually have little circular vesicles, which are a limited resource, that you put the cubes on, and they move down the chain as you are first filling them with protein and then filling them with lipids and, and carbohydrates and then pumping them out of the cell at the end. And so will you necessarily learn cell biology off of this? Maybe not, if you're just playing it just as a game, but if you did this and then you took a course on Cell Biology, would it suddenly make a lot more sense and be easy to learn? Heck, yeah,
Brian  27:54  
Yeah. I think that's and that's kind of what I think is the point here, is like the cell is a little factory, right? And you are making, doing the little factory, and you're right, if you played Cytosis, and then you come to the class, it's like, Oh, I already know all of this, right? I learned all of this from that great game. What was that called? Yeah, I think that that covers most of the points. There's this very minor thing where, if you've made a receptor, and somebody else makes the matching hormone, you get, like, bonus points for that, and you get more points if someone else does it, which, again, is this idea that hormones are for, mostly for communication between cells. But yeah, cytosis basically is this wonderful tour through the cell, and they really do a good job of representing, in a very simple way, the basic processes of of a eukaryotic cell doing its eukaryotic cell things.
Jason  28:40  
Yeah. And that said, we never actually defined the other type of cell, which is the prokaryotic cell. Which is everything else. And frankly, they outnumber us by probably, like, a billion to one or something. These are the bacteria, and technically, also the archaea, but they basically, they look the same under the microscope. These are your tiny, little, single cell things, they're much, much tinier than eukaryotic cells by and large, and they're much simpler. They don't have a nucleus. Their  DNA is mostly just free floating as large circles. They do have ribosomes, but they don't generally have any other organelles. It's only been about 30 years that we have what's called the three domain model of life, which is the you have, the bacteria, the archaea, and then the eukaryotes. And that was developed in the 1990s when people started looking at these ribosomal RNAs and putting together and realizing, like, oh, wait, the Archaea aren't some like, weird little branch of bacteria. They're their entire other domain that have been evolving separately for three or 4 billion years from bacteria
Brian  29:40  
Like you and an elephant and a mushroom have way more in common with each other than a bacteria has with an archaea.
Jason  29:47  
Oh yeah. I mean, these things are separated by billions of years of evolution.
Brian  29:51  
I want to pop in a little hot take on bacteria and organelles, if I could. So again, the defining trait for prokaryotes or bacteria is that they don't have organelles. Right? They've got all of their stuff just free in their cytoplasm. Except one of the major classes of bacteria have two sets of membranes. They've got an inner membrane and an outer membrane, and they have a defined space in between those two membranes with different functions, different enzymes, different targeting. Sounds an awful lot like an organelle to me. 
Jason  30:21  
I mean, when you're wrapping the entire cell in a second one, it's not really an organelle. It's a it's an interstitial space.
Brian  30:29  
Just going to point out that we all learned that our skin is our largest organ, and I'm going to say that the periplasm is the  organelle of bacteria. But again...
Jason  30:37  
Okay, touche, touche. This is just a thing. Brian was trained on this type of bacteria. I was trained on the other type of bacteria, and so I like them better, and he likes this type better. And we're not going to get into all the differences there.
Brian  30:53  
We haven't found a good game to talk about bacteria yet, so we're going to have to look for that. So let's get into the nitpick corner.
Jason  30:59  
You're more nitpicky than I am, so you start 
Brian  31:02  
Okay. So first of all, I don't mean this as a criticism. I mean this is just a sort of a fun exercise. So one of the things about cytosis is that it's a worker placement game. You're in a cell. What are you as the player, exactly? Competing inside of this human cell to get health points? Like, you got five people competing in one cell to use the factory of the cell to do what? Like, it's hard when you're not sure what you're personifying. Do you know what I mean? 
Jason  31:28  
So I'm going to posit that since in Evolution, we were apparently playing nature spirits and nature gods. I'm going to posit that we are playing cell spirits and cell gods. They're very, very tiny ones.
Brian  31:39  
So I have a, I have a different interpretation. I think that we're playing transcription factors, the programs in the cell that will control expression of different types of cell parts, right? The things that turn different sections of DNA on and off. I feel like maybe that makes sense. What you have is multiple competing transcription factors, sort of competing for control of a single cell. 
Jason  32:04  
You know, I could see that with everyone have their own agenda, like this one's trying to turn on the protein export synthesis. This one's trying to turn on the enzymology here, and you're all going around, there's not a finite pool of resources we're all competing for. So technically, all the resource cubes are infinite. If you run out, you just find something else to fill them in. So I guess that's the one thing where that doesn't quite hold up. But no, I can see that. 
Brian  32:29  
But I guess you're competing for access to the cell machinery, right? 
Jason  32:32  
True, true.
Brian  32:33  
Okay, so the other thing is a little bit of the mixed metaphor of we're using flasks inside the cell, and that's just weird. We're like, using these little chemistry flasks. So it's like, are we humans controlling an individual cell? It's like, because the cell doesn't have little flasks. This is totally pointless, but I want to put, I'm going to point people towards this in the show notes, there are these wonderful little motor proteins. They look like they walk on the cytoskeleton, are these like filaments of protein that move and connect all the different parts of the cell. They look like tiny little sorcerer's apprentice brooms that carry vesicles from place to place. So I wish, instead of having little flasks, we had little kinesin meeples. They're really cute. Please look at it if you're if you're listening to this, please go to the show notes and check it out. They are goofy. And they haul around like, you know, like, oh, ants can carry 10 times their weight. These things are carrying things that seem like they're 100 times their size, just dragging them around the cell.
Jason  33:29  
And they have a cute little walk too. So if you actually look at videos of them walking, it's like they're just kind of like moseying around, like some little, like, 1950s cartoon character just kind of loping down its pathway. They're actually they are very cute.
Brian  33:42  
They literally walk like I'm not, that's not a joke. That is, they actually walk. It's crazy. And would that be perfect for Cytosis? No, because it's not for every part, but better than flasks, maybe.
Jason  33:54  
I guess you could put like little cell meeple, but a flask is easy, 
Brian  33:57  
But, but a kinesin is cuter.
Jason  34:02  
Then how would you have third party groups selling upgrades to the game? 
Brian  34:06  
All right, if there are legitimately third party groups selling little kineeples, I want a kineeple.
Jason  34:12  
Well, if there aren't, you could probably start 3d printing them and put them on Etsy, because they, I mean, if I've looked at some of the games we've played, there are so many awesome upgrades that it's like, unfortunately, they usually cost almost as much as the game itself in order to do the upgrade, but they look very cool.
Brian  34:27  
We're in a weird hobby. Do you ever think about that? Yeah, do you have any little nitpicks about the game? Yeah, any little Do you have any little nitpicks?
Jason  34:36  
I guess? I mean, you know me, I like player interaction, and I kind of wish there were a way to interact with other players that was not so much, I just steal your spot half by accident. But if there's something I could do that would just make your life just a little bit more difficult or cost a few resources to get rid of, and maybe that's what the viral expansion is. There's, there's an expansion this game that introduces viruses. You have what? You have the flu, you've got Ebola, yeah, a cold and Ebola. And one of these viruses is not like the others. Yes, it's like, people do die from the flu every year. Yes, the cold can kill people, but then you have Ebola, yeah? It's like, okay, we have escalated the scale of the virus. Anyway, that's a side tangent, but maybe that's a bit more that happens there, because skimming over those rules, there may be more ways of mucking with other players based on what viruses show up and what you do with them.
Brian  35:33  
So we should. We're running a little short on time. We haven't talked about when we played the game yet, so we had a special thing happen this time for me in particular, I haven't beaten Jason in a game since...
Jason  35:44  
Not for this podcast, You've beaten me in some games we've played just in our family game day.
Brian  35:48  
Sure, occasionally, but in this game, we tied on points. We used completely different strategies. We tied on points, and then we checked the book to see, Okay, what about the tie breaker? Oh, the tie breaker is, well, how many cell component cards have you made? We tied again on that, so we double tied on this game.
Jason  36:05  
Yeah, I think at that point we invoke the Evolution rules of ordering pizza and playing again.
Brian  36:10  
I think there was something else where it just said, you just choose a random winner. Basically, it's like, no, we're not going to do that. So let's do our report card. Let's start with the Science report card. So we've talked about how we have our skills set a little differently for the science, for me, it is, how much science are you going to learn, whether purposeful or non purposeful, by playing this game? With sort of B is our starting point. With wingspan as our A, Cytosis, for me is an A plus. I don't know how you could do better. I really don't. We have, obviously have curved grades, but like, this is, this is more that this is an A plus. For me
Jason  36:46  
I'd also put it solidly in the A, A plus range. I mean, this is right up setting the standard for how you have a game that is fun, which we'll get to in a bit, but also a game that is, that teaches you things about science while you're doing it. It's not just a skin painted on top of it. It is actually an integral part of the game. And you learn things even if you don't know you're learning them by playing it. So, yeah, I think this is totally A territory.
Brian  37:10  
Why don't you list out on how much did you enjoy the game?
Jason  37:14  
I'm gonna put gameplay also up in A territory. This is, I think, a very well balanced work replacement game. I think they're multiple strategies you can pursue. You can adjust your strategies based on the other people. There's enough spaces to have options, but they're scarce enough that you that you always want to try to grab the best ones first. I felt like it was making me think and making me plan and try to react to what you were doing a lot, and that's my metric for a good work replacement game. So I put this also in A territory.
Brian  37:44  
And for me, my fun is, how likely am I to grab it off the shelf, you know, throw it in the car, bring it to game night, or just whatever? And cytosis is one of these games. We don't play it all the time, but I have pulled it off the shelf and wanted to play it routinely, which is, I've got plenty of games that that's not the case for. I was excited to play cytosis again. We still haven't played the virus wxpansion. We'll actually have to do that at some point. 
Jason  38:05  
Yeah, that may or may not be enough to make another episode off of, but, yeah, we'll do that at some point.
Brian  38:09  
This is an A this is, I think this might be our highest scoring game. Is that true?
Jason  38:13  
I don't remember what we gave wingspan on the, I mean, I think it also got A's on both. I mean, it's it, it's A for science and...
Brian  38:21  
yeah, wingspan and cytosis, I think, have been our highest scoring at this point. 
Jason  38:24  
Huzzah, we now have two games we can compare everything to, instead of always having to talk about wingspan! If anyone out there really hates wingspan, I'm sorry that you have to hear about us talk about it so much, 
Brian  38:37  
Although I gotta be honest, I have yet to to meet someone who doesn't like wingspan. Much like Catan was that starter game for a lot of people, you would be amazed how many people have played wingspan, just people who don't play games play wingspan.
Jason  38:51  
Now we need to get cytosis into more people's hands. So that is probably time to wrap it up. Thank you all for listening. Hope you had fun. Have a good week and happy gaming. 
Brian  39:01  
Have fun playing dice with the universe. See ya.
This has been the gaming with Science Podcast copyright 2024 listeners are free to reuse this recording for any non commercial purpose, as long as credit is given to gaming with science. This podcast is produced with support from the University of Georgia. All opinions are those of the hosts, and do not imply endorsement by the sponsors. If you wish to purchase any of the games that we talked about, we encourage you to do so through your friendly local game store. Thank you and have fun playing dice with the universe. 
Today, we're going to discuss cytosis both the heck was that.