S2E02 - Gut Check (Microbiome) | Gaming with Science

#Microbiome #GutCheck #SciComm #Dysbiosis #Antibiotics #Probiotics #GameDesign #BoardGames #Science

Overview

In this episode we talk with Dr. David Coil, microbiome scientist and the creator of Gut Check. We talk about microbiome health, antibioics, probiotics, prebiotics, game design considerations, and how the game's origin includes cheerleaders and the International Space Station.

Timestamps

0:00 Introduction
1:17 Microbiome body odor & sweat
4:47 Gut Check overview
10:45 Microbiome science
17:02 Antibiotics and phage therapy
23:05 Prebiotics and Probiotics
26:59 Game history & design
41:52 Giving the game away
47:01 Grades & final thoughts

Full Transcript

(Some platforms truncate the transcript due to length restrictions. If so, you can always find the full transcript on https://www.gamingwithscience.net/)

Brian 0:06
Hello and welcome to the gaming with science podcast where we talk about the science behind some of your favorite games.

Jason 0:12
Today, we'll be talking about gut check published by Qiagen. All right. Welcome back, everyone. This is Jason.

Brian 0:20
This is Brian,

Jason 0:21
and we have another special guest on today, Dr David Coil. David, would you please introduce yourself?

David 0:26
Hi. Thank you guys so much for having me on the show. My name is David Coil. Right now. I'm the program manager for a National Science Foundation funded center on pandemic Insights, where we study what we call the pre emergence phase of pandemics, which is viruses circulating in animals that might jump to people and cause problems.

Brian 0:45
Very cool. Maybe we should have had you on the other game. We didn't know.

Jason 0:48
Hey, we can't have everyone on the pandemic episode. We have to spread them around. I'm sure there will be other disease related games we can go over.

Brian 0:55
Yeah, probably

Jason 0:56
anyway. So David, we wanted to get on here. Because not only is he an avid gamer and scientist, he's actually the chief creator of gut check, which we're going to be going over today.

Brian 1:07
Yay.

Jason 1:08
This is less going to be an interview. We mostly want to talk the science, but we do want to get some insights from you about the making of the game, the things involved in that. But mostly we want to talk about microbiome science before we get to that, though, we would like to start off with some cool science fact. As our guests, we give you the first choice. If you have some cool science fact you've learned lately, you can share it. Otherwise, I'm sure Brian has something to share.

David 1:27
It's funny, I actually tried to think of something. But in the spaces I work in, all of my science facts are depressing for a fun I mean,

Brian 1:37
we just did a paleontology game. And you know, they always point out that the best Paleontology is founded by tragedy, so

David 1:45
fair enough.

Brian 1:46
Uh, well, I did find something. And maybe this is not depressing, but possibly entertaining. I usually try to theme them. So this is the microbiome of underarm odor.

Jason 1:57
This sounds like it's heading for an ignobel

Brian 2:00
No, not at all that you would be amazed at how many studies there are. I don't know. I maybe you wouldn't. I'm not sure. Okay, so underarm odor is not produced by your underarm. It is produced by the breakdown of things that come out of your apocrine glands, by the microbes that live in your underarm. There is a dipeptide, so two amino acids stuck onto a thiol alcohol. It has some name that's quite complicated, so I'll stick with thiol alcohol. Thiol means sulfur, so a lot of stinky compounds tend to have sulfur in them. The alcohol, I assume, just means it's very volatile, which means it's going to spread through the air very easily.

Jason 2:36
And now I see why you got this, because your whole thing is stinky plant compounds all made os sulfur

Brian 2:39
Exactly! There's actually a deeper connection here. So I study onions, garlic and that type of defensive chemistry. There is a very meaningful connection here. The compound itself doesn't smell like anything. It's odorless. Supposedly, I found a couple of things that said it actually is an antimicrobial in and of itself that it can bind to ureases and actually can kill bacteria. So bacteria, particularly Streptococcus hominis, which as you can imagine, it takes this name because it lives on people, will take this compound up. It splits off those little amino acids, presumably uses them as food, turns them into pyruvate, uses in its primary metabolism. And then it's got a specific enzyme, a carbon sulfur lyase, that will split off that sulfur thiol alcohol, so that it's no longer toxic, which then gets exported out of the cell and smells real bad. So this is the same type of enzyme that gets, truly gets used by onions and garlic to produce their defensive compounds. So that's that's how I learned about it. But yeah, same kind of deal. I did see another paper where they figured out things that could inhibit that process, so that you don't stink as badly.

Jason 3:42
So this reminds me, I read a book all about sweat a few years ago, and yes, that's a weird book to read, but it's one of those like, let's take a an everyday thing and look into the science of it. It's actually quite fascinating. But the author talked about, believe the author was a woman, she talked with someone who was investigating, essentially, microbiome treatments, like skin microbiome treatments to change your body odor so that you don't have as bad body odor. There's this whole story about this guy who picked up bad body odor from his girlfriend and then trying to treat that so that anyway, there's this whole story. I'll link it in the show notes if you want to look up an entire book about sweat.

Brian 4:20
You know, I do remember hearing a couple studies that people tend to share their microbiome that like people in a single household. Yeah. Is that true?

David 4:26
Yeah, no, no, for sure. And if we get into the topic of fecal transplants, which is my favorite topic of conversation, doing it from someone in your household is useful for that reason.

Brian 4:36
We talked a lot about poop in our paleontology episode too. It sounds like this is going to be a common running theme, maybe this year,

David 4:42
Microbiologists just love to talk about poop.

Jason 4:47
All right, so let's get on into this game, then gut check. So gut check is a little bit of an unusual game. Most of the games we go over, everyone we have gone over so far is a commercially published game. This one is not quite in that space. This was a game that was designed as almost an educational outreach. You said you had a grant from the was it Sloan Foundation to do communication and outreach?

Brian 5:09
Oh, that's very cool.

Jason 5:11
I like first that you actually have a scientific paper talking about the game. We did a bonus episode on Publish or perish. I like the way of actually being able to turn a game into a publication that you can not perish by anyway. I like how you talked in there the the problem of making a an educational game that is actually fun, because most of them aren't. In fact, we've talked on this podcast before about how the term educational game is almost a dirty word in the gaming industry, because the idea is that if it's educational, it can't be fun. And so this game was essentially your goal to try to hit both of those the same time. So for those of you haven't played it, which is actually going to be quite a lot of you, because it is not commercially available. It is, however, free to print and play. So it is Creative Commons licensed. Go to microbe.net, you can download it, print it off, play whatever you want, which I imagine, is how a lot of like teachers and university classes are getting traction on this. Now, it was briefly published by MoBio and then Qiagen, but they decided not to continue that. Unfortunately, turns out, if you're in the business of extracting DNA from cells, it doesn't make much sense to continue publishing a board game, much to our sadness.

Brian 6:16
I was at the ASM micro meeting last year and they had copies of gut check. It's like, Oh, that's really cool.

David 6:21
They still have it. They still have it, and they give it out as prizes at conference and things like that. So it's available through QIAGEN, but you can't order it. You have to earn it or win it, or convince someone to give it to you,

Brian 6:33
which I wish I had taken the time to go to the Qiagen booth and convince them to give it to me, because I didn't realize I couldn't go and just buy it. I definitely would have made a point otherwise.

Jason 6:42
I'll have to see. I'm going to a conference this next week. I'll have to see if I can sort of extort it out of them, even though I already have a copy. It's just like I need to get more of these out in circulation to people.

Brian 6:52
Well, I need a copy, so you should get it for me,

Jason 6:55
fair enough. All right, so what does this game actually consist of? So typical board game components, there's a large central board where you track points. Points in this game are health, and you each have your own player board where you track the microbes and diseases that you have picked up. There's a deck full of microbes, beneficials, pathogens, so diseases and harmful ones, and also a bunch of opportunistic ones, which can be either beneficial or pathogenic depending on circumstances. And that plays into some of the strategy of Do you want to play a beneficial on yourself or a pathogen on someone else? Player age is 13 plus, although, apparently, David, you mentioned in one article that you had your six year old daughter play, and she quite enjoyed it.

David 7:33
The reason it's 13 plus is because of the edibility of the pieces. If you want to make it for younger ages, you have to do toxicity testing on your pieces. This is something I learned. I learned all sorts of weird things through the process of designing a game that, as a gamer, I was unaware of, I would have happily put eight plus on the box, but then you have to test the components.

Jason 7:55
How many eight year olds are still eating game pieces?

David 7:58
I don't know who came up with these rules anyway.

Jason 8:04
So two to four players, ages 13 plus,

Brian 8:06
legally,

Jason 8:07
legally, yes, you can. You can give it to younger children, just at

Brian 8:12
at your own risk

Jason 8:13
Well, it's more at their own risk. Don't feed the game to your children. You should be fine. And the goal of the game is just to accumulate health points over the course of it, which happens through a few cards that you can play. Like, if you have microbes that can digest certain foods, you play those foods, you get health. You can lose health by aside from pathogens and diseases, there are certain things that can happen. Like, for example, getting a round of antibiotics can decrease some of your microbes and also slightly decrease your health. There's these gut check cards that basically are a semi random way of checking how your microbiome health is at the moment, and that will determine your score, will make it go up and down. And the goal is basically that whenever the draw deck finally runs out, you have the highest health, or ideally, you get to the maximum, which is like 50. No one's ever done that in any of the games we played. And especially, you don't fall to zero, which is where you die. And no one ever did that in any of our games, either. So

Brian 9:05
I got down the health track quite a bit. A few times. I'm actually not very good at these games.

Jason 9:10
didn't you win the last one we played?

Brian 9:12
absolutely not

Jason 9:13
okay,

Brian 9:14
not even close.

Jason 9:15
Okay. So those are all the components of the game. Playing the game. You draw your cards, you're playing your microbes on yourself, on someone else, you're playing diseases. You're playing treatments like prebiotics, that's microbe food, which basically lets you play more microbes, probiotics, which lets you get a random beneficial microbe, various other things. My favorite card in the entire deck, and maybe we'll talk about this a little bit, is the homeopathy card. So the homeopathic treatment, which literally does nothing.

Brian 9:41
Yeah, it's a pointless card,

Jason 9:43
which I love that, because I think that's an important thing to put in there. If there's any of our listeners who are great devotees of homeopathy, I'm sorry you may enjoy your placebo effect as much as you want, but it's still just a placebo effect.

Brian 9:55
So I only played the we only played the commercial version of the game that was provided to Jason. Thank you. By the way, my favorite thing about the mat in the middle is it's just a depiction of the intestines, and that's it. It's sort of like it's the there's sort of a dead skull on one end, and then there's the other end, where, I guess the maximum health you would go out the whatever. We don't need to talk about it in detail. But I was like, this is this person has no stomach. They have no mouth. This is only a human from the perspective of the microbes,

David 10:23
it's a schematic. It's a gut schematic.

Jason 10:27
Well, from the microbes point of view, we are basically just a walking thing of habitat, and most of them are in our gut. So like, what else matters?

Brian 10:33
Yeah, it's just that the bits that are around the gut are of no concern,

Jason 10:37
kind of like how we only care about, like, the 100 yards or so, plus or minus the surface of the earth and maybe a little bit of that atmosphere. Stuff. Anyway, let's get into the science of this. Now this is where I really want to get into things. So I am actually a plant microbiome researcher. That's what my research is on. Even though I don't study the human microbiome, I do kind of keep abreast more or less of major things. And when I was starting graduate school like this was just barely a new thing. We could barely even touch the microbiome. Microbiomes because the technology to to look at these and had just barely been made, but now they're everywhere. I say you can't throw a rock without hitting some new paper saying, No, the microbiome is important in this thing and that thing and all these stuff, things like depression, heart disease, behaviors, obesity. I think we're still trying to sort out how how much of it is. It's a cause versus a symptom. But the fact is that people are finding links all over the place, and it pops up all over the place on YouTube, Tiktok, whatever, which now brings us to our core thing, David, what's a microbiome?

David 11:33
You know? And I'm glad you asked that. And as you just mentioned, you know, microbiomes are everywhere. But, you know, I designed this game 10 years ago, and at the time, it was still very much an emerging Wild West sort of, sort of science. I feel like things have settled down a little more. We have a better handle on the tools and what it all means. But a microbiome is just a collection of microbes in a context, and it may or may not be biologically meaningful. We could talk about the microbiome of the planet, which might not be meaningful, but in this case, we're talking about like the human gut microbiome. We're just saying all of the microbes that are typically found in the human gut. But it still gets very difficult on the edges. You know, there's lots of microbes that are transitory because they came off your food. Are those part of your microbiome or not? The microbiome is actually a fuzzy concept. It's clearly really important in a lot of places, but it's, it's fuzzy on the edges.

Brian 12:26
It's kind of like an ecosystem, right? What are the edges of an ecosystem? Yeah, it's fuzzy.

David 12:30
It is an ecosystem, actually. And that, that's probably what makes it so important.

Jason 12:34
Next question, then, is like, Okay, we all have microbiome we have many microbiomes. We've got the gut, skin, inside the mouth, like pretty much anything that touches the outside world has a microbiome, I think, is it still thought that all our interior tissue is still pretty sterile. If things are going right?

David 12:49
If things are going right. But like we used to say that urine is sterile, and we now know that that's not necessarily the case, even without pathology.

Brian 12:58
Oh, interesting. Okay, so humans are a tube, right? So anything on the outside and anything on the inside,

David 13:03
yeah.

Jason 13:04
then why is the microbiome important? You have all this gut health and gut microbiome, what's been found about how this actually impacts our health? I rattle off a few things, but I'm sure you have a much better idea of this.

David 13:16
Well, just you know, the microbes in your gut, for example, can help you digest any number of things. They make a lot of compounds, you know, more digestible, more absorbable. They also perform what we call niche exclusion, like you have happy, warm places inside you, and if they're full of beneficial microbes and there isn't space or opportunity for pathogens to grow. So I think that's a really important part of the human microbiome. It's just already having something living in all these nice, warm, moist places, which makes it harder for bad actors to come in and play. And so as you say, we're discovering more and more every year about how important the microbiome is and potential effects on the brain and mood and neurological conditions. And it's just fascinating how quickly you know, 20 years ago, to most people, microbes are bad, are bad, and they're something you want to avoid at all costs. And I think now our understanding is much more nuanced. Of course, it's also swung the other way. You know, there's a lot of snake oil and things out there about, you know, pop this pill and magic happens.

Brian 14:26
Do you think that societally, we've kind of shifted to some microbes are bad, some microbes are good, or do you still think it's kind of a mixed bag in terms of how well that, sort of, like, made its way out into society?

David 14:38
It's mixed. But, I mean, if you look at, you know, the yogurt section of the store, and, you know, the active cultures and probiotics and prebiotics and like, you know, there's, there is definitely, I think, an understanding that microbes can be beneficial, the nuances of that, though, I think we still don't really understand all the details,

Jason 14:59
yeah, and so. Was one of my follow up questions is, I know there's a bunch of, as you said, snake oil out there. I mean, anything that has even the potential of being something to improve health, people will latch on and they'll slap a label on it, and they'll start selling you at a 10 times markup. How do you find reliable information about microbiome, what actually causes a benefit? What is possibly snake oil. Are there trusted sources or trusted people to check with?

Speaker 1 15:23
I mean, that's a really good question. You know, a study will come out saying that this microbe was found in higher abundance in healthy people, as opposed to unhealthy people, for some condition, obesity, for example, and then immediately there's people packaging and selling it. But I think a lot is confusing, you know, correlation and causation, right? We don't know in many cases which direction things go. You know, maybe your microbes are different because you're healthy or because of some underlying confounding factor, right? It's not that having this microbe will make you lose weight or will make you happy or whatever, right? So I think there's, there's a lot of confusion of this idea of correlation and causation. You know, the published scientific literature is not perfect, but it's, it's a lot better place to start than than TikTok, I would say, if you're information on on microbiome health. But to some extent, for me, personally, I put it in the same category as nutrition, in the sense of, there's paper saying coffee is bad, there's papers saying coffee is good. And you know, our feelings about fat and sugar and all these things change over time. But broadly, if you eat a relatively balanced diet that consists of a lot of different things that don't come out of a can, you're probably all right. And I would say that same general approach probably applies to microbes. If you don't hit yourself with antibiotics too often, and you eat a balanced diet, your microbiome will probably be happy. That's probably good enough for most people, in most cases, unless you want a fecal transplant. And that's a different story.

Brian 16:59
I hope we get to get into that just a little bit at some point.

Jason 17:02
Well, let's head into that, because you mentioned antibiotics. a few times now, and so tying that together, what I know is that one reason why you want to be cautious with antibiotics, and I guess, quick aside, antibiotics are a wonderful invention that have revolutionized health,

Brian 17:17
saved lives.

Jason 17:18
Oh, they've saved millions upon millions of lives. But that doesn't mean you should use them anytime you want. It's like they should be used carefully. And maybe David, you can get into the various reasons, like, why do we want to be careful about using antibiotics as opposed to just using them anytime I start feeling sick?

David 17:33
Yeah, no. I mean that. That's an excellent question. I think this is, again, also something that as sort of a society, we're shifting in our understanding of when it's appropriate. So, as you point out, I mean, they're, they're a fantastic invention. I say invention. They're not really invented by us. The vast majority of antibiotics are produced by other microbes, right? And they use them for their own purposes. You know, there's a whole arms race out in soil of antibiotics being produced by some bacteria and then defenses by other bacteria. And there's a whole ecosystem out there, and we just sort of steal from that.

Jason 18:02
I keep saying that nature looks like it's in harmony, just because everything is out to get each other all the time. And so it just looks balanced because we've reached equilibrium, but they're really just all out trying to kill each other.

David 18:12
They are. They are, and that's where most of our antibiotics come from. And so if you have strep, you have strep throat to be common you want to take antibiotics. I mean, strep can actually lead to pretty severe complications in some cases, and so you take antibiotics, it knocks those bacteria down, your microbiome, re-equilibrates , and you're doing well. But the problem is, antibiotics are not specific. We had antibiotics that knocked out just a particular bacteria. That would be amazing, because then we could just take that and knock out. But they're not. They're generally, you hear this term broad spectrum antibiotics. And broad spectrum means they kill a lot of different things, and so they kill not only necessarily the pathogen that you're after you hope, but also many of the beneficial microbes in your body. And that's where you start to have a problem, because you disequilibrate the system, and in severe cases, you're in a hospital, you need to be on antibiotics. Maybe you're having surgery, or you had a severe infection, and you you knock out your microbiome so badly that a single bad actor can take over. So this happens in hospitals with Clostridium difficile, C diff, it's a really nasty usually, hospital acquired infection, and it typically appears in people who've had antibiotics and you have a single bacterium that takes over the whole gut, and it can be lethal if it's not treated.

Brian 19:31
Oh, geez, I didn't realize that.

Jason 19:32
And this goes back to what you were saying about beneficial sometimes they are beneficial just because they're occupying space and they're keeping a bad actor from getting in and taking over. It sounds like this is what happens you what happens you do antibiotics or basically a scorched earth on your intestines. And if you're unlucky, then that means that there's a new opportunity for C diff to move in and take over. Is that about right?

David 19:52
Yeah, no, that's about right. And this gets to, you know, we have to talk about fecal transplants, and the best use case for fecal transplants is, in fact, in this scenario where you have a single bad actor, and that bad actor, that C diff, is often resistant to numerous antibiotics, so you can't take more antibiotics to solve the problem, but you can give an infusion of beneficial microbes. So you take someone that has a healthy gut microbiome, you take feces from that person, you inject it into the gut, and you sort of give that ecosystem a chance to re establish itself and push out the bad actor. And it actually works really well for that purpose.

Brian 20:30
So, just to go back to the ecosystem analogy, I think we've already said it. This is the antibiotics are clear cutting the forest, right? And you've got individuals that are able to, I mean, there's a whole field of disturbance ecology. That's basically what a post antibiotic intestines is, right? Is a disturbed ecosystem where something can come in and take over all of that niche space, but it can still be pushed out by a healthy ecosystem that's reintroduced.

Jason 20:54
Yeah, I was actually just looking this up, and I like how you represented this in the game. C diff is one of the pathogens in the game, and when it's in play, whoever has it, they can't add any beneficials, except through probiotics. So basically, the intentional addition, they can't just be colonized by something. You have to actually intentionally take it or do the fecal transplant card, which I think what gets rid of all the negative ones?

David 21:16
Yeah, fecal transplant knocks down all the pathogens.

Brian 21:20
I noticed there was one card in the game that seemed to have no downside, and that was the phage therapy. Can we talk about that for a bit?

David 21:27
Sure, phage therapy is still pretty new. So bacteriophages are viruses that specifically attack and kill bacteria. So phages don't present any risk to human health. They don't impact human cells. They go after bacteria. The idea of using phages to kill bacteria specifically is relatively new, at least in the United States. It's actually something that the Soviet Union has been working on for many, many years. But there was a disconnect for a long time between science that happened behind the Iron Curtain and science that was being published in the West. But I think it's, it's equilibrating a little more now, but the the attraction of that is the specificity of the phages. So this idea that you could have something that's more specifically targeting a particular pathogen, you had a particular phage that went after that, and that might not impact the rest of the microbiome, I'd say we're still in the very early days. But that's, that's the attraction and the the promise of phage therapy.

Jason 22:25
And so those of you who don't know what a phage is, you've probably actually seen one. If you've ever seen a little cartoon of some little virus that looks like, like little 20 sided die on a stick with spider legs. That's a phage

Brian 22:35
a lunar lander?

Jason 22:36
Yeah, they look really cool.

Brian 22:38
So they often get used to depict viruses where, like, unfortunately, human viruses are usually really boring looking. Bacteriophage look real cool, so they tend to get used inappropriately to represent viruses. Because why wouldn't you want something that looks like it's got little legs, like a little weird spider with a gem head,

Jason 22:55
although now I think we're probably getting variations of COVID representing human viruses since that well, Pardon, pardon? The phrase went viral.

David 23:01
Yeah, that's what we see now. Is enveloped viruses.

Jason 23:05
So we've talked a few times now about like, prebiotics and probiotics, which are both cards in the game that you can play. But can you tell us a little bit what? What are those two things? What's the difference between them? Are either of them worth using?

David 23:17
Sure. So prebiotics, as you mentioned earlier, are basically food for beneficial microbes. The idea is that there are certain compounds, fiber falls in this category, that we don't necessarily digest directly, but that beneficial microbes can use. And so we're sort of nudging our microbiome in a beneficial direction by giving them certain foods that beneficials can use probiotics is just the act of taking live, active bacteria. So if you have active culture yogurt, that's basically a form of probiotics, both of them, scientifically, are very clearly established concepts. The use of them for improving human health, I would say, is murkier. You know, when you take bacteria orally, so active culture yogurt, how much of that is going to survive passage through your digestive system, through the, you know, very inhospitable environment of your stomach and and actually get into your gut and do something useful there. And also, you know, maybe what my gut needs at this moment is different from what your gut needs. So it's hard to say, you know, there's a universal, you know, little, little probiotic that you can drink, that's, that's necessarily useful. I think there is some evidence showing that after antibiotic treatment, so after you've knocked down your your microbiome with antibiotics, there's some benefit in in trying to re establish a healthy gut microbiome with probiotics. So I'd say they're both scientifically useful concepts, but I wouldn't say it's clear exactly how to apply them commercially for health.

Brian 24:48
In the game, some of your beneficials help you digest certain things, like you said, fiber, plants, dairy, there's one more I'm forgetting. What am I forgetting? Jason,

Jason 24:56
vitamins. They don't digest vitamins. They make the vitamins.

Brian 24:58
That's right. It's grains Dairy, plant material, and then vitamins, making the ultimate food, pizza, right? That was that's actually in the game as well. The best card to play is pizza. Which I like that? I think it was lasagna in the print to play.

David 25:11
Well, it's funny, because there's things like that that, you know, it was lasagna in my mind, because I was finding something that had all these different components to it. But when Qiagen printed the game, they insisted it had to be pizza. I don't know why, and there's other weird things like that, where I had these you could go on a bus trip or a plane trip, you know, which is the idea of you're sharing microbes with other people, and that's what happens in the game. But they insisted to add like, a train trip and a boat like I don't know why.

Brian 25:43
There's four different types of trips. They all do the same thing. It's just pass microbes to the left or to the right.

David 25:47
I had one was to the left and one was to the right. So I had train trips to the left, plane trips to the right. I don't know why they decided to add boats.

Brian 25:55
Were there any other changes that they wanted to make, or that they made that you know of?

Jason 25:59
there was a significant art upgrade. That's the most visible change, probably,

David 26:03
in the print and play version. The artist who designed the print and play version was very thoughtful about ink usage, so the print and play cards are designed to not destroy your you know, ink cartridge.

Brian 26:15
Oh that's great. That's actually really considerate.

David 26:18
And that's a different consideration when you're printing. Also, every company out there has, you know, a certainaesthetic. They have, you know, fonts that they used or whatever. And so there's actually two printed, commercially printed versions of the game. There's the MoBio version, which has the MoBio color palette and fonts. And then when they got completely absorbed by Qiagen, Qiagen then reprinted the game, and they redid all the art. It's the same pictures, but it's with a Qiagen set of fonts and color palettes.

Brian 26:47
Oh, man, I gotta go try to find on eBay the MoBio version somewhere so I can have the whole set.

Jason 26:52
Good luck. I looked up. I couldn't find even to used copy.

Brian 26:55
You couldn't find it either?

Jason 26:56
I couldn't find a used copy for sale anywhere. So okay,

At one point I want to talk about the weird, the weird history of the game and how it came to be offered as a promotional item by Qiagen

David 27:07
Well, that story of the game, we were doing a project where we sent a bunch of bacteria to the International Space Station to see how they grew in microgravity compared to Earth, actually collected with the help of professional cheerleaders around the country. So you can see why I did a lot of media interviews.

Brian 27:21
This is, this is this is okay, sure,

Jason 27:24
professional cheerleaders, as in, like the people cheering on of like

David 27:27
NFL, NFL and NBA cheerleaders

Brian 27:29
collected your microbes to send to the space station.

David 27:31
It's a long story. Anyway,

Brian 27:31
it sounds like someone did an like a mad lib of just combining words

David 27:33
It the awesome project, but I created baseball cards for all the bacteria that were going to the space station, little trading cards that had, like, a fun fact. And then so the and we would give these out at promotional events. We were trying to get people engaged in, like, getting excited about these bacteria that were going to space and my boss asked me if we could gamify those cards, like, like pokemon or something like that, turn them into a trading card game. And I thought about it, and I decided, no, I just I couldn't see any hook or any interest. But I said, you know, it would be cool to design a game about the microbiome. And he said, We should absolutely do that. Said, Okay. And then I said, I want you to repeat in front of all these witnesses. It was like at a lab meeting, there were like 20 people there, and I said that you want me to spend my time at work design board game? Yeah, and so I started to think about it, and then off we went. So yes, I got paid to design a board game that was very exciting,

Jason 28:29
awesome. That's great. And along those lines, so you decided not to gamify the little collectible cards. But I know a few other people have maybe not a game out of it, but they made them collectible. This conference I'm going to next week. Every year, there's one or two companies that they have the little collectible cards of, like the genomes they've sequenced and stuff. And every year I seek them out, just so I can add to my collection. But my little binder here, of all my little genome cards that have no real value whatsoever, other than I think they're cool

Brian 28:57
my chronically disorganized office, I thought I had a little stack of these cards. I have the mulberry genome. I think it's up on my card thing on the wall next to all of my Oddish cards.

David 29:06
Yeah. Well, people were excited to take these cards at a convention or whatever, but as a Magic the Gathering nerd myself, for five years, I couldn't see a way to gamify it.

Jason 29:16
All right, so there's one other thing I want to talk about, the mechanics of the game that you represented, because you did take care to try to represent real scientific concepts mechanically, and that's horizontal gene transfer, which I think we may have mentioned in past episodes, but it's not something that you usually hear about, but unless you're actually a microbiologist or in biology. In the game, when you have a bacteria that's gotten Antibiotic resistance because it survived your treatment of antibiotics, then you can play a card that will actually move that resistance to another bacteria, which I assume that the idea is that if you have any harmful resistant ones, you can move that to a beneficial one so that it doesn't get nuked the next time you use that antibiotic. But this represents real biology going on. So David, can you explain a little bit of. Like, what that's representing, how it works in in the wild, so to speak?

David 30:03
Sure sure, but, but in game terms, you can also make your opponents pathogens resistant to more microbes with lateral gene transfers so that they have more trouble getting rid of Yeah. So in real terms, so I guess we'll talk really briefly about antibiotic resistance. So microbes, as I said, they're living this battle in the soil, on plants or wherever they're fighting with other microbes. And so they've evolved a lot of defenses to protect them against antibiotics. And so a really common form of antibiotic resistance is a pump, so bacteria have pumps that pump out the antibiotics so they don't damage the cell. And so if you have the right kind of pump, and when you're exposed to that kind of antibiotic, you can just pump it out of your cell and survive. That's a common defense against antibiotics. It's a way that bacteria are resistant to those antibiotics. And there's many different forms of antibiotic resistance. Some of those happen just naturally through mutation. You know, if you expose bacteria in a dish to an antibiotic over and over again, some of them are going to acquire resistance to it, through some mechanism or another, and eventually, all of the microbes in that dish will be resistant to that antibiotic because you've kept them under what we call selective pressure, you've kept attacking them with this antibiotic, and only the ones who are resistant to it survive.

This is listeners. Why, anytime you're prescribed antibiotics, you finish the course of antibiotics, even if you feel fine, because otherwise you're doing that exact same thing inside your body.

and you're still potentially doing it even if you finish the course of antibiotics. Right? You know it makes sense that when you continually apply some threat, the things that are resistant to that threat survive. And this is a problem, because over time, as a society, when we use antibiotics, we create these multi drug resistant bacteria. And so if you think about MRSA, is a methicillin resistant staph aureus, it's a problem in hospitals. But in the past, you know, it had become resistant to methicillin, which is a kind of antibiotic that is used a lot, and if you had it, then we used something else. We used a different antibiotic, vancomycin, say, to treat it. But now we have these strains, these, they're called XDR these, these multi drug resistant strains, where they're resistant to most, or maybe all of the antibiotics we have. So you have in a single bacterium, they have all these different resistances, and we can't kill them. And some of those bacteria are lethal. And so people die because they've acquired these multi drug resistant strains of bacteria. Where it gets really interesting is that some forms of these resistances can actually be transferred from one bacteria to another, and that's the horizontal gene transfer. So if the resistance is, say, encoded on what we call plasmid, it's a separate piece of DNA. It's not part of the genome of the bacteria. It's a separate free floating piece of DNA that can actually get transferred to another bacteria, and that bacteria can become resistant even though they've never seen the antibiotic. And so one of the concerns with the overuse of antibiotics is that you create resistances, and those resistances can then be passed out to other bacteria. So that's a concept I really wanted to convey in the game, and this is one of the places where the lateral gene transfer card in the game is not very useful from a gameplay perspective. It's the card that gets discarded most of the time. But I really wanted to convey this idea, the resistance that could be transferred between microbes.

Brian 33:32
I felt that in the game it's like, this is a really cool mechanic. I appreciate why that's here. It's hard to use, so I didn't end up using it very much, but it's like the homeopathy does nothing, and that still needs to be there for the purposes of being entertaining.

David 33:45
There's a balance between education and entertaining. And, you know, I've listened to a lot of your guys' podcasts are really, really interesting. And, you know, the vast majority of those games didn't exist 10 years ago. We now live in the sort of post wingspan era. Of, you know, teaching people cool science with an interesting, beautiful game is is more commonly accepted. And, you know, as we talked about at the beginning of the episode, I was frustrated with the fact that most educational games, the gameplay was very weird. And in particular, I've always been frustrated with this concept where you're faced with a choice in the game, but it's an obvious choice. I should either do this thing which is clearly good or this thing which would be stupid, then I don't feel like you're making real choices. And I really wanted a game where I felt like when you looked at your hand, it wasn't obvious what you should do, like, oh, do I want to play a beneficial on myself? Do I want to hurt someone else? Like I wanted that process where you have to strategize about your choices.

Brian 34:43
Let's get into game design just a little bit. So I had a question, how did you choose which pathogens my wife got the plague a bunch of times when we played there were only 10 different pathogen cards, and I think only four different pathogens in the version that's published by Qiagen. How were those selected? Because they weren't all gut microbes.

David 34:59
So when. I designed the game. Everything just had placeholder names. You know, good bug one, bad bug three. You know, as I was doing the massive amount of play testing that game design requires, because there's a balance, right? If you have too many pathogens in the game, then, you know, everyone dies all the time. And so, you know, I did hundreds of hours of play testing, and most of that was just with placeholders and then once I felt like I had an appropriate balance in terms of number of cards and types of cards and things like that, then I went out and tried to find things that made sense. And I think I actually talked about this in the paper. In the beginning, I had something that digested meat, because that kind of made sense to me. And I went out into the scientific literature, and I couldn't find any evidence anywhere the bacteria that helped you digest meat.

Brian 35:47
I think meat's pretty easy to break down, right?

David 35:49
Yeah, but I couldn't find it. So maybe, you know, the body does all the work, and you don't need the microbes for that. So I had to shift to something else, and I switched to grains, which numerous people have pointed out to me over the years that grains are plants, so it doesn't have grains two separate categories. But yeah, for for choosing the the pathogens, you know, I had to have things like C diff, because it made sense of this concept of resistance. And botulism is another food borne thing. I tried to find things also that people had heard of. So the plague is in there, not a gut microbe, but it's something that people have heard of. So I thought it would be interesting. So it's maybe, maybe not the most scientifically interesting, but, but something that would be familiar to people.

Jason 36:32
And you have to admit, the game appeal of just giving other people botulism and the plague and stuff, there's a certain amount of fun in that.

Brian 36:39
Oh, for sure. No, I was teasing my wife. She needed to stop hanging out with so many prairie dogs, because prairie dogs carry plague. I think one of the hardest things to to deal with, with antibiotic resistance, and I know I even have graduate students who really struggle with this, is that it's the it's an act of selection, the resistance existed. It's just, you've eliminated everything that was sensitive, that's always hard to communicate. It's not that taking antibiotics creates resistance that selects for the resistant individuals.

David 37:07
Yeah no, that's true, and that's a difficult concept to convey. And in the game, it appears that resistance is created, right? Because you treat with antibiotics and then you get rid of half of your beneficials, and then the other half become resistant. But you're right. That's not what's happening. You're selecting for the things that are resistant.

Brian 37:25
Could you let us see behind the curtain? What was a mechanic that sort of got dropped during play testing?

David 37:30
Oh see, this is like a memory test. Now, that was a long time ago and and I've kind of blocked it out, I mean,

Brian 37:39
so that that might go into my next question is like, would you design another game? Or do you have an idea for another game that you'd like to design? Or is that, are you have you left that part of your life behind?

David 37:47
Well, I think I mentioned this actually in the paper the if you've done enough play testing, you should never want to play your game again. And everyone you know should never want to play you know, I hosted a weekly Friday night board game group, and by the time the game was published, all of my colleagues and all of my friends never wanted to see it again. You know, when we got shrink wrap copies of it, I gave everyone a copy as a thank you, and they're probably mostly still in shrink wrap on everyone's shelves because everyone was traumatized by the iterative play play testing is is really quite painful. And I mean, I spent many, many hours putting my PhD to good use using a paper cutter cutting out cards, because I would print them on card stock, I would cut them, and we'd play, like, two games and be like, this doesn't work at all, or like, this doesn't make any sense. And so I'd go back and I make adjustments, and I'd print them out again. That's why, when people asked about like, could you make an expansion? Like, people have asked, Could you make like, an STD expansion?

Brian 38:47
Oh, gosh,

Jason 38:48
Gut check after dark. Oh,

David 38:50
exactly. I don't. I don't think I want to do that. I don't want to revisit that process.

Brian 38:56
That was people's top requests. Was STDs?

David 38:59
I had multiple people request an STD expansion

Brian 39:02
or STI sexually transmitted infection, I guess we call it now, but

David 39:06
I don't think I want to revisit that space. I would consider designing another game, but there's so many things I would do differently. The biggest which I would I would want to understand the publication and distribution process in advance. I mean, I didn't know what I was doing when I made this game. I did all the play testing, I got everything ready, and we were going to spend grant money from the Albert P Sloan Foundation to print it, and then we were just going to sell it to recoup our costs. And that's where I discovered, do you have a problem? Because if I hand you the game and collect $20 I'm obligated by the State of California to collect sales tax on that transaction and then file that sales tax as a business. And I didn't want to do that. I didn't form, I didn't want to form an LLC file business taxes. Or I just wasn't interested in that. And, yeah, I hadn't thought about that in advance. I was like, oh, we'll just spend grant money to make it and then, you know, we'll recoup our costs, but it doesn't work that way. So we could have spent a bunch of grant money and just given it away and not recoup our costs, but that didn't make sense either. So the game sat for like, a year as I tried to figure out what to do. And everybody's like, well, Kickstarter, you know, exploding around that time, and everybody's look good Exploding Kittens, they made, you know, a million dollars in five days. I was like, Well, yeah, this is not going to do that, you know, I'm not the oatmeal, and it's a ton of work, as you pointed out Brian. So I sat on it for a long time, and then I just, I cold called MoBio, and I said, I have a proposal for you guys. I'll give you this game, just everything you need. You put your name all over it. You pay to print it, you give it out as a promotional item, and you give me enough copies to like, you know, give to friends and family, and that's what they did. I didn't realize at the time that I had not thought of this as an educational game in the context of like high school and college classrooms. I was thinking about gamers and biologists. Those were our targets. It became very popular with high school and college teachers, and I started to get a lot of requests for copies of the game to use in the classroom. And I wish I had thought about that use case in advance, because I would have done two things differently. First of all, I would have made sure I had copies of the game to give to people for education purposes, but I would have designed a shorter, simpler game, you know, had a lot of people using a game in a high school classroom. You can't explain this game and play it in a 45 minute class period.

Brian 41:28
Oh, yeah, that is hard.

David 41:31
The game is too complicated for like, non-gamer high school students to pick up quickly, and it takes too long to play. So in that sense, if I had wanted to design a game that would be used in education. I would have designed something like a deck of cards that was more portable, simpler, and just got at those concepts without all the complexity.

Jason 41:52
Before we started recording, you were mentioning something about the university actually getting upset with you for giving the game away to MoBio. Can you go into that in a little bit more details and maybe share what you're allowed to share

David 42:02
well as a staff member of the University. And this is different for you guys, because you guys are faculty, they have different IP protections. You know, if you invent something, you have some personal stake as a faculty member in you know, when you go through your tech transfer, office, etc, as staff, the university owns you, basically. And so if you create things, the university is supposed to, you know, own the rights to those things, basically. And so by creating the game and releasing it under a Creative Commons license, that was a violation of the spirit of that policy, at least. And so when the discussions about this came up, the university was asking, but who owns the copyright? And it's like, no one, because I released it under an open Creative Commons license. And they're like, but, but who owns it? Like, does MoBio own it? I'm like, No, and Qiagen doesn't understand this either. Qiagen has all the files, and they have everything, and they can make more copies of this game. But this idea that, like, no one owns the rights, I think, is not intuitive to either industry or academia.

Brian 43:07
Yeah, I could see this being a problem, because at that point it's like, well, then how do we make money on it? That's, well, you don't, you don't make money on it.

David 43:14
Someone can take the cards off of gut check, put it on T shirts, sell it, and make money. And, like, that's all allowable because it's an open license.

Brian 43:22
Jason I were talking about adding some sort of, like, game upgrade items to our website, which we could totally do, because it's creative commons, right?

David 43:29
You can do whatever you want with it.

Jason 43:30
Yeah, our top choices were a tip card for, like, what you can do in your turn, because we kept having to reference the Rule book for that, and then making little 3d printed antibiotic resistance instead of the cards. I understand why you did the cards, because those are probably much cheaper to print than custom little tokens, but giving people their own 3d print files to just make a few antibiotics seems like it'd be easy enough.

David 43:51
That would be really cool, and I really regret the fact that I didn't have a tip card, like a rule summary card. There's any number of regrets. So in preparation for this episode, I sat down with my two teenage daughters, and I played my game again. It's been many years. I relived the trauma, and I found all sorts of things to be critical about. I was like, Oh, I wouldn't do that again, or that was a mistake.

Brian 44:14
Let us know what you what you would change. We have every opportunity here to make the changes. We could say they are. "David Coil approved".

David 44:21
Well, one of the biggest issues is you guys reviewed pandemic. You've played pandemic.

Brian 44:26
We did

David 44:27
The way the epidemics are spread throughout the deck. You know, you make pile.

Brian 44:31
Oh, the gut check system reminds me of the pandemic outbreak system.

David 44:36
It is very similar, except that they're totally random throughout the deck, which is a problem I was trying to avoid the hassle with games like pandemic, we have to create a bunch of piles, and then you have to shuffle a card into each pile, and then you have to stack the piles, right? But the the utility of that is, you get some distribution of these checkpoints. In gut check. You just chuck them into the deck. They're totally random, but that means that the game can be very swingy from like a point perspective, so you're doing really well at this particular moment, and there's three turns in a row where a gut check comes up that's going to massively balloon your score, or whatever, or be really frustrating if you just happen to have a nosocomial infection, and a couple of pathogens when that happens. So I think it's it adds to the randomness in a problematic way, to have the checkpoints be totally random. So I think if I were to do it again, or if I were to make an addendum, I would do something more like pandemic, where they're distributed.

Brian 45:32
but then that also is kind of counter to that well, but I want something easy to play in a high school classroom. So it's like, this is the thing. It's always a choice. It's always a balance. It's like, is it the game balance? Is it the educational component? It is a time constraint.

David 45:45
Every game suffers from those choices, which is why there's house rules, right? So many people, you know, I like this game, but there's this one thing, and so, like, we're gonna change this,

Brian 45:53
but that's the joy of a board game, as opposed to a video game. Well, I guess now you can mod a video game, but you want to play a board a board game differently, you just play it differently. If you don't like a rule, you just don't like a rule, you just don't use it. If you want to add a new rule, you just do it.

David 45:53
It's true as long as everybody's on the same page.

Brian 46:06
The number of times I've played a board game, many, many, many times the wrong way, only later to realize, Oh, that's not the rules. This game seems really out of balance. It's because you're playing it wrong, but you were still having fun. Everybody was still playing by the same rules.

Jason 46:19
I'm not convinced that anyone actually plays monopoly by the real rules.

No, nobody does. I mean, monopoly is the classic example of an educational game that is no longer educational, right?

Yeah, it's actually, I think it was a plot point in the movie heretic that just came out about how it was originally meant to teach the evils of capitalism. And then someone decided that, hey, this could be a fun game. I'm going to take it, remove the moral lesson, and just sell a bunch of it.

Brian 46:41
There was another game where it was like, I can't remember what it was. It was monopoly. And what was the name of the opposite game on the other side of the board, cooperation, or something. Well, the cooperation part was boring, so nobody wanted to play it

David 46:52
You know, monopoly is interesting. If you play with the actual rules, the game is actually much faster than with all the house rules that people typically play with.

Jason 47:01
So we're getting near time. So it's probably time to wrap up. Normally, what we do is we give a letter grade to the game in terms of how it did in terms of science and gameplay. I feel really weird doing that with the game creator.

Brian 47:12
Do you want us to grade you? Because it feels weird.

Jason 47:15
I wanted to ask David, you said you recently played it. It was obviously wasn't just sparkles and rainbows. Of reliving your game. What would you give the game in terms of, how good was the gameplay? How good was the science? Like, how did it represent the science you wanted to represent?

Brian 47:30
I love this compromise. It basically puts it completely on the Creator.

David 47:34
Yeah, no, this is interesting. After listening to a bunch of your episodes, I was like, I'm gonna be the first game creator. So I'm curious how they're going to do the the grading part,

Jason 47:44
simple, we we delegate.

David 47:46
I'm totally comfortable if you grade and criticize the game well, so let me do the science first. So I think the science is is not perfect,

Brian 47:54
but it can't be. It never can be, right?

David 47:58
I feel like the game did a good job at conveying the scientific concepts that I wanted to convey, especially about this idea about opportunistic microbes that, like everything's not black and white. It's not, you know, the Rebellion and the Empire, the good guys and the bad guys. You know, context matters, and so microbes can be good in some contexts and bad in other contexts. That and the concept of antibiotic resistance and the trade offs of the use of antibiotics and the fact that, you know, beneficial microbes can help you digest things. I feel like those concepts came through in the game. There are important mechanics in the game, and I've gotten a lot of letters over the years, and people reaching out on Twitter and things like that, where people like, hey, my teenager learned something from this game. So I feel like the game was successful from a scientific perspective, even though, of course, there's corners cut about the science the gameplay is where I'm more critical, because I feel like the game is too swingy from a points perspective, like a good game, to me, is someone who's played it a bunch is going to consistently beat someone who hasn't played it until they learn the strategies and nuance. If it's random, who wins, then I feel like you haven't succeeded as a game designer in doing something that requires strategic thought. It's a little harder to sort of pick up and play than I would like. I don't love the instructions. You read through the instructions the first time, you're like, Okay, don't quite get it. And this is something I learned as a game designer. That's because the instruction is the very last thing you do hours of play testing. You got it all figured out. You know the rules by heart. Everyone you play with knows the rules by heart. And then you're like, crap. I gotta write all this down, and then it sort of gets done at the end. That doesn't go through that iterative process to the extent that it should. So I'm gonna give it a b minus for gameplay. Oh,

Brian 49:46
Oh that seems unduly harsh. I think you're being too harsh. I really do.

David 49:50
Well, it's like when you talk to an artist though, right? Like everybody criticizes their own work.

Brian 49:54
yeah, so we're gonna, we're gonna inflate that a little bit. I think the gameplay, I think it is fun. I'm always worried that the bias of, hey, I'm a card carrying microbiologist, maybe how much this is influencing me. I don't really care. It's a B, let's be honest, not a b minus. That's a fun game. You definitely get the A out of the science. From my perspective. Jason, do you? Do? You agree with me? You agree with me, right?

Jason 50:15
I'm thinking because, again, I was trying to, I was trying to recuse myself from being put in this position, but no, I think like B for gameplay is good A, maybe A- minus territory for the science, just because part of me thinks that if it's a gut check game, they should all be gut bacteria. But that's a that's a little quibble, to be honest.

Brian 50:33
That's true. We didn't do our nitpick, did we? I guess my nit pick was that you don't get plague in the gut.

Jason 50:38
That's probably just it. And I think also, we have gotten spoiled by deep science games. There are several that we've gone over that have an amazing, like, very huge amount of science in them where, like, each card has its own little fact and everything. And so it's like, it's hard to compare to get some of those. I think David your your evaluation, is spot on, it does what it set out to do.

Brian 50:58
And it was also, it's a pioneering game. Like you said. This was 10 years ago. This was pre wingspan. This was pre the sort of boom in science and educational games. This was, have you had a chance to play, like cytosis, for instance, or any of the games from genius games, where the sort of hard science concept is at the at the center?

David 51:14
I played some of them, yeah. And, I mean, I had one called pathogenesis. Oh, there's a lot of really cool science games out there, and they come much prettier boxes, much more effective, the boxes we don't need to talk about that I tried to explain to them, that gamers have a certain expectation for what a game box looks like, and this they produce is not it at all. on a shelf In a thrift store, you'd be like, that's not a real game because there's an aesthetic to what a game looks like on a shelf, and they did not care. But anyway, yeah, I love many of those games, and I love the fact that science games are popular.

Jason 51:51
all right. Well, I think that's we're going to close down here. I will say, if any of you listening to this, are aspiring game designers and want to cut your teeth on gut check v2 you would now have not only a bunch of ideas to do so, but you have permission, because it's all Creative Commons. So you can go out and do it and publish it, and publish a paper on it, and there you go. That's how you can get started with that. Just gonna say, Thank you, David for coming on. This was great having you here. I liked doing this as something that's very dear to my heart with the microbiome science, but also something that was made by a scientist to teach science and see that other side. As we said on here before, educational games sometimes get a bad rap. And I'll be honest, your paper did not dissuade me from that. As you mentioned, all these educational games I had never heard of,

Brian 52:32
we haven't found a good game to talk about bacteria. So honestly, for that reason alone, I loved being able to play gut check, and I was excited to get the printed copy to do so. David, where if you wanted anybody to reach you, you said you've gotten letters and things. First of all, do you want people to be able to get in touch with you? And second, where would you like them to be able to do that?

David 52:50
The best way to get in touch with me is on social media, either x or blue sky. And it's David A Coil,

Jason 52:57
All right. So any of you who want to play gut check to go ahead and look it up at microbe.net we'll put the link in the show notes, and until next time, have a great month and happy gaming.

Brian 53:05
Have fun playing dice with the universe. See ya.

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S2E02 - Gut Check (Microbiome)

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