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Have you ever wondered how biologists choose what animal to use in their research? I mean, we can't do a lot of basic research on people, so scientists study animals to shed light on human health and genetics and how our brains work and whatever the case may be. And yet, just a couple creatures appear over and over again. And it raises the question, why the mouse? Why the fruit fly? Why the zebrafish? Well, each of them has a different appeal depending on what you're studying. But there is one thing all of these so-called model organisms also have in common. Export Grade Walnut Kernels
CASSANDRA EXTAVOUR: When we try to choose a model organism, fundamentally, we're looking for convenience.
SCOTT: This is Cassandra Extavour, an evolutionary biologist at Harvard.
EXTAVOUR: For us to work with it in the lab, it can't be very big. So elephants are mostly out.
SCOTT: Ideally, they reproduce quickly so there are a lot of generations to study.
EXTAVOUR: So also, elephants are mostly out. We'd like it to not be very expensive to maintain, so maybe not very picky about what it eats or drinks.
SCOTT: And also doesn't need to be raised in super-specific environmental conditions.
EXTAVOUR: And so because of that, a lot of model organisms that are commonly used, like mice or fruit flies, are organisms that are garbage-feeding organisms that will live anywhere on anything, that are often considered pests in the natural world.
SCOTT: Cassandra and her lab work with a number of different organisms, but in recent years, they've published several papers praising a new model critter on the block - crickets.
EXTAVOUR: The main things we're doing with crickets right now - one is to understand how genes control which cells get fated to make eggs and to make sperm in the cricket. And in a second line of research, some people in the lab are using the cricket to study brain stem cells, which can produce new neurons that help the cricket learn and remember things.
SCOTT: And before we get into what makes them a good model organism, I'm just curious what you think of them as creatures. I mean, are there things that you love about crickets? Are there are things that, you know, you find ridiculous, surprising, delightful?
EXTAVOUR: To be honest, my opinion about crickets is sort of neutral to slightly grossed out. I find them a little bit disgusting, and it's mainly because they remind me of cockroaches, which I find very disgusting. And so I don't have any special fondness for the crickets, but I appreciate that it's - they've taught us a lot about some really interesting biology.
SCOTT: Spending day in and day out with something that makes you squirm - that's dedication to the job.
SCOTT: So leave the mouse to its maze. Today on the show, we are going to consider the cricket and all of the amazing things it can teach us. I'm Aaron Scott, and you're listening to SHORT WAVE, the daily science podcast from NPR.
SCOTT: Dr. Extavour, let's talk about what makes a cricket kind of a star candidate for model organisms. What do they offer that other model organisms, like the fruit fly, don't offer?
EXTAVOUR: Things that we can do with the cricket that we can't do with another model organism, like the fruit fly, I would say come in two main flavors. One, crickets, like most insects, in their adult brains, have some stem cells, as well as all the neurons that are, you know, controlling their behavior, that can produce new neurons during life that can help the crickets remember things and learn things. Fruit flies don't have stem cells like that in their brains. Now, what's interesting about that is that humans, we don't have stem cells like that in our brains, either. But wouldn't it be amazing if we did? Because part of the basis of many neurodegenerative diseases in humans is that when neurons are lost in our brains, we can't get them back. We don't have a way of making new ones.
So if we can understand what is it about the cricket brain that lets it have stem cells during its adult life, then maybe, eventually, in the future, that might help us understand, what is it about human cells that prevents them from being able to do that, and are there ways to coax human brain cells into becoming more stem cell-like? And I would say the second sort of flavor of problem that we can study with the cricket that we can't study with the fruit fly, we think it's probably most likely that a last common ancestor of all the living insects did have stem cells like this. And that's why most of their descendants have these stem cells. But fruit flies lost the stem cells over the course of evolutionary time.
So fruit flies aren't great models to help us understand what was probably the ancestral way of making an insect. But crickets seem to have many more of those conserved features of what we think an ancestral insect development might have been like. So that second major group of problems that we can understand with crickets that we can't with fruit flies are problems about the evolution of insect development.
SCOTT: And that gets at some research that you have done looking at germ cells - correct? - that our understanding of kind of how germ cells form based off of fruit flies was maybe not a good model for a lot of other creatures.
EXTAVOUR: Right, exactly. So our best understanding of germ cells, which are the cells that make eggs and sperm, comes from traditional model organisms like the fruit fly. And in that organism, the way that you make germ cells is that you actually begin preparing to make those eggs and sperm way back in the egg stage. So in the egg of the fruit fly, there's a special collection of molecules that get made inside the egg and partitioned into a specific corner of the egg. When the egg is fertilized and develops into an embryo, the cells that form in that corner of the egg inherit this special collection of molecules and they become the germ cells because they've inherited it.
SCOTT: So they're kind of like an exclusive club hanging out in one spot and maintaining themselves over the development of that embryo.
EXTAVOUR: Exactly right. It's like there's an exclusive club over in one corner, and if you make it to that corner, they hand you a cup and it's a special drink and you drink it, and now you've got the stuff inside you that's automatically going to make you able to be - to make eggs and sperm in the future.
So that's how fruit flies do it. And it's a really well-understood mechanism of making germ cells. And for a long time, it was thought to be the ancestral animal mechanism of making germ cells. But mice and potentially other mammals are probably not using that mechanism. Instead, they basically just tell a neighboring cell, hey, you should get ready to make eggs and sperm in the future. And that cell just says, OK. It didn't drink anything special, but it got a special message from a neighbor.
So what was interesting about the work that we did in the cricket about germ cells was we looked for evidence that a special group of embryonic cells were going to that corner and collecting this special drink. We didn't see any evidence of that. Instead, we did see evidence that at a later stage of development, some cells were sending a signal to neighboring cells saying, hey, prepare; in the future, you must make eggs and sperm. That was really surprising to us because we thought we would find the secret club drink mechanism. And it suggested a possibility that was new, which was that maybe this specific way of signaling might have been a much more ancient way of making sure that animals have germ cells than we had understood before.
SCOTT: That's fascinating. And all of this gets to the idea that diversity is really important when it comes to model organisms, correct? I mean, should there be a portfolio, really, that scientists are working with that spans quite a lot of diversity?
EXTAVOUR: A hundred percent. Absolutely. I mean, we were saying that model organisms are so important to scientists because at least we can have some degree of control over them. And yet, at the same time, it's just one organism, and it might or might not be telling us the generalized principles that we'd love to learn about other organisms. So on the one hand, of course, it's not practical, it's not feasible for us to study every organism in every laboratory. At the same time, we always want to be contextualizing what we find and comparing it with what other people are finding when they study other organisms.
SCOTT: I'd love to talk a little bit about crickets' potential in use for medical research. Can you say a little bit about them as disease models and maybe for development of pharmaceuticals or other medical research?
EXTAVOUR: Sure. We were very fortunate to recently get support from the National Institutes of Health for our studies of cricket stem cells in the brain. In speaking with the program officers at the NIH, they said that they were very interested in potential new models for the study of brain function and brain pathologies. And it could be the case that crickets could be a useful model for adult brain stem cell activity. And you can study some cells that may be long-lived or long-lived neuronal progenitors in mice, but mice are extremely expensive to work with in labs, and so crickets may provide another alternative model to helping understand some of these unique brain functions that might have to do with memory and learning because of their adult stem cells.
SCOTT: I was shocked to learn that crickets can learn by things like observation, that they can watch another cricket and then learn from what that cricket experiences in the world.
EXTAVOUR: They absolutely can. Crickets can learn by observation, as you said. They can learn by smell, olfactory learning. So they can learn that certain smells are associated with things that they like, rewards, or things that they don't like, punishments. And they'll learn to go towards the reward or go towards a certain smell that they've learned is associated with something they like.
SCOTT: I was very intrigued by something I read in one of your papers that they also have the potential to be biological factories for pharmaceuticals and that we could breed them to have health-enhancing properties to make them as health foods or medicines. Can you say a little bit about that?
EXTAVOUR: Sure. The idea there is that because there are genetic modification techniques available for crickets, meaning it's possible to introduce genes into their genomes or to slightly change the genes that they have in their genomes, it could be possible to modify crickets to make them more nutritious, for example, for making them express higher levels of enzymes that will then help them produce lots and lots of different vitamins that humans might be interested in consuming or, potentially, other molecules that humans might be interested in purifying and then consuming for pharmaceutical reasons.
SCOTT: Since you were a postdoc and you first started working with crickets, have you seen the focus on them really grow? Like, do you feel like there is momentum behind this, or do you feel like you all are kind of, you know, a little boat out at sea screaming against the horizon?
EXTAVOUR: Well, not quite that dramatic.
EXTAVOUR: There are definitely more labs working with crickets now than there were when I started. This laboratory in Japan of Dr. Sumihare Noji was really one of the first labs to establish these functional gene analysis techniques in the cricket. But, you know, since I was a postdoc, I've learned of, you know, another four or five or six labs doing the sort of functional genetic analysis that we're interested in with crickets. Crickets, in general, have actually been a model for learning and behavior for many, many decades. And because they have very interesting learning abilities, they have very interesting behaviors and you're able to train them to do different sorts of activities and it's also possible - my colleagues in the fields of neuroethology and neuroscience have worked out ways to visualize and record the activities of the neurons of the cricket while they are doing these interesting behaviors. And so even beyond developmental genetics, which is my field, many other fields of biology have been using crickets for a long time. So I think they're here to stay.
SCOTT: I love it. Dr. Cassandra Extavour, it has been a delight to talk crickets with you. I didn't realize what wonderful little creatures they are.
EXTAVOUR: Thank you so much. It's been great to talk about them with you. And you're welcome to come by the lab anytime and see some.
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SCOTT: Before we go, a quick thank you to all of our + subscribers out there. They get our episodes sponsor-free, and they make a huge difference in supporting our work. If you want to join them, learn how at plus.npr.org/shortwave. This episode was produced by Thomas Lu and Brit Hanson, who also checked the facts. Our editors were Gabriel Spitzer and managing producer Rebecca Ramirez. Our audio engineer was Tre Watson. Brendan Crump is our podcast coordinator. Beth Donovan is senior director of programming. And Anya Grundmann is senior vice president of programming. I'm Aaron Scott. Thanks, as always, for listening to SHORT WAVE from NPR.
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