In this episode of Tiny Show and Tell Us, we cover exciting new 'living robots' called xenobots — made from frog cells with the help of a supercomputer — and what they might be used for down the road. Then we challenge how much "junk" really makes up "junk DNA" and discuss the regulatory sequences and other things our DNA codes for that aren't functional proteins.
Transcript of this Episode
Transcript:
Sam Jones: Welcome to Tiny Show and Tell Us, the bonus series where you write in with your favorite science story, fact or piece of news, we read your email aloud and then dive deeper. I'm Sam Jones, the Exec Producer of Tiny Matters, and I'm joined by my fearless co-host, Deboki Chakravarti, who is back from maternity leave.
Deboki Chakravarti: I'm back, I'm so excited. I feel like we had just started doing these before I left, and so I'm excited to get back into it and remember how to do these.
Sam Jones: Yeah, we'll figure it out.
Deboki Chakravarti: Yeah. I'm a little rusty listeners, please have patience. Before we get into things, just a reminder that Tiny Matters is always looking for you to write in because that is what makes future episodes possible. You can email us at tinymatters@acs.org, or click the Google form link that we put in the episode description. So let's go then, let's start.
Sam Jones: Let's do this. Okay, so listener Finn wrote in saying, "Xenobots are synthetic biological robots capable of cooperation, directed and autonomous activity, and self-replication." And then put in parentheses, "Nuts!!!" It is nuts, yeah. And then, Finn had some questions about these xenobots, which I'm going to get into. But first, what are xenobots? You probably want to know if you haven't heard of them before. They are cells that are assembled into living robots about a millimeter in size, and I'm going to share a link to a video in this episode's description so that after you listen you can go and look at these things in action.
The first report of xenobots was January 13th, 2020, in the journal, Proceedings of the National Academy of Sciences. And so, originally these things, these living robots, were designed on a supercomputer at the University of Vermont, and then they were assembled and tested by biologists at Tufts University. Okay, so let's talk about that assembly. To create these xenobots researchers used stem cells that are harvested from early frog embryos, specifically the African frog, Xenopus laevis. If you've ever done a developmental biology course you've probably heard of Xenopus because they're a really, really important organism for developmental biology studies.
In a dish, these cells began to differentiate into different cell types, and what the researchers did was they used skin cells plus added in cells that would eventually become heart tissue. And then, they cut and joined together these cells into different blobby structures essentially using these tiny forceps and an electrode and then following, of course, the computer program's design or designs, there were many. And so, what was wild to see was that with certain cell configurations the cells began to work together. And so, the skin cells formed more of this passive architecture and the contracting heart muscle cells were what allowed the xenobots to move, which is just wild to think about.
Deboki Chakravarti: I'm still really stuck on tiny forceps, tiny doesn't seem like it even covers it.
Sam Jones: Nearly microscopic, no, I don't know.
Deboki Chakravarti: It's very cute too, actually, when you think about it. So what they found was that these xenobots could move toward a target. They could work together to push objects from one place to another and they could also heal themselves after being cut. They would move around in their watery environment for days and sometimes I think around a week or so because they had the energy to do it. Before I get into some of Finn's questions, I thought it would be important to know why would they ever make these little living robots? One of the big, exciting reasons to study xenobots is because they provide some insight into how cells in a living, moving thing actually work together. You're seeing, if we design these little blobs to have cells in these places, like different cell types in these places, how will they move? How will those cells interact? And so, you're able to learn a lot about cellular interactions and locomotion with these living robots.
A big application that people talk about with xenobots is cleaning up pollution, so thinking about designing these xenobots to actually move in a certain direction, maybe they carry something with them or there are a bunch of different approaches to cleaning up pollution. Also, of course, they could be used to grow replacement tissues. Some people think maybe one day they could be designed to help replace organs, which is huge. Again, this is very, very, very early days but still really fascinating to think about.
Sam Jones: So Finn asked a few questions. One was, "How are xenobots accessing and using energy stores in their tissue?" Which is a great question because like, okay wait, you clump these cells together and they move around but where is the energy coming from? And they self-renew and they heal themselves, and so they use energy from fat and protein that's naturally stored in their cells. Actually, embryonic energy stores are pretty high so that store of what's ultimately energy lasts about a week, and then the cells die. But apparently you can keep them in what I saw referred to as a soup of nutrients and they can last for months, but I had trouble tracking down exactly what combo of nutrients that could be.
Deboki Chakravarti: Yeah. Sounds very serum-y.
Sam Jones: Yeah, like they're putting them in a serum that has sugars and proteins and fats, and the cells are able to use that to stay alive. And they do seem to generate energy the way that most cells do, using cellular respiration where they break down sugars to make ATP.
Deboki Chakravarti: I wonder ... I'm sure the researchers have thought of this and I'm curious, can they integrate plant cells in there at all to be able to somehow use light to generate nutrients that'll then power the xenobot?
Sam Jones: Oh, that would be really cool, and it's totally possible that someone's already been working on that and I just didn't come across it because this is a very new but very exciting area of research. And so, I feel like there's probably a lot of people potentially working on how to create a fuel source that's integrated into these xenobots so that they can do their thing for months and months and months and not have to be in this nutrient soup or whatever it's called. Okay, so then Finn also asked, "If xenobots were allowed to grow in the wild and were successful, would, should or could they be considered alive?" Which was an interesting one and also an interesting thought experiment.
Deboki Chakravarti: Yeah. Definitely a real philosophical dilemma at some point.
Sam Jones: Yeah. I mean, so I think first off they are referred to commonly as living robots so that already kind of makes me feel like yes, or at least trending toward alive. And then, one of the computer scientists and robotics experts at the University of Vermont who co-led the initial study said in a press release, "They're neither a traditional robot nor a known species of animal. It's a new class of artifact, a living programmable organism." And so, that would also be another point in the alive category but I think also when you ask should they be considered alive, could they be, it gets really complicated too because these scientists are already talking about building xenobots out of different types of cells, including human cells, and I think that's where things start to get a lot trickier.
It makes me think a lot about Episode 71 where we talked about bio-hybrid robots that are a mix of living and nonliving materials and some concerns that the expert we interviewed, Vicki Webster Wood, had about working with human tissues. One of her thoughts was, until there's real understanding of if these robots can feel pain, she just wasn't okay doing anything ethically unless it was for medical use in humans so this is a really tricky topic for sure.
Deboki Chakravarti: Yeah, it's so weird when you break things down into cells like that and how, is it like Ship of Theseus, or I forget which one, but the one that's like once you start to deconstruct a ship and replace all the boards on it, at what point is it a new ship? I feel like this feels a little bit like that, when you start to take cells and put them back together in new ways at what point is it an organism again?
Sam Jones: Right. Definitely the terminology surrounding xenobots to me says that they are viewed by, at least the researchers who work on them, as living because they are living cells, right? They're living, they heal, they replicate.
Deboki Chakravarti: At some point, isn't the point of a robot that it's not living? I don't know, I'm not as up to date on my robot terminology.
Sam Jones: I don't know. That was sort of my understanding too but maybe that's changed and we're just not in robotics and we don't know that.
Deboki Chakravarti: It's true, yeah, that is true. Add it to our list of things we don't know as much about.
Sam Jones: Please, if someone is listening and they work with robots, you should write in to Tiny Show and Tell Us, and tell us what you do.
Deboki Chakravarti: We got to start doing a bring your scientist to work day.
Sam Jones: I know.
Deboki Chakravarti: We bring somebody on.
Sam Jones: Yeah, totally. And even just for writing in, your science factoid can be your research. That's really cool.
Deboki Chakravarti: Yeah.
Sam Jones: Anyhow, so Finn had just one more question which was, "What can we learn from the researcher's use of evolutionary algorithms to develop these bots and where else can we apply these lessons?" Something that immediately comes to mind for me when you're talking about algorithms is drug testing, so getting a sense of if something will work before moving into testing in the lab and putting a bunch of money into something. Actually, computationally trying to do an analysis to predict what will and will not work. It also makes me think about plugging tiny matters as I'm doing Tiny Matters stuff.
But it also makes me think back to Episode 70 of Tiny Matters where we talked about the evolution of pesticides and pesticide resistance and how computational evolutionary analysis is actually allowing researchers to predict which pesticides insects will become resistant to or maybe already are because of some genetic mutation that occurred millions of years ago. So I just feel like the computational biology space holds a ton of promise in a variety of fields.
Deboki Chakravarti: Yeah, that's really exciting.
Sam Jones: Yeah. So thank you so much, Finn. This was a fun one to research, I definitely learned some stuff with this.
Deboki Chakravarti: Xenobots is such a great name also for a technology, I feel very Saturday morning cartoon, but in a good way …
Sam Jones: I know.
Deboki Chakravarti: Exciting. Yeah. Cool. Well, Sam, I'm coming to you with a question from listener, Tammy. Tammy asks, "I just listened to the ancient viral DNA episode and it got me wondering about junk DNA. Do we call it that because we don't know what it does or do we call it that because it doesn't affect the human body in any obvious ways? Could it be protection against things that no longer exist or what do we think it is? I want to know so much more." That is a great question, Tammy, and there's layers to this. There's a short answer, a long answer, an even shorter answer I feel like. That shorter answer that I'll just jump right to is that scientists are still answering this question. And so, I'm going to start with my initial short answer, which is that junk DNA is DNA that's not really serving any function in the body. But the long answer is really actually a bigger question of what does function even mean?
When we talk about DNA, there is a clear idea of one function of DNA, right? We're talking very simplistically what DNA does as it encodes proteins. You have your sequence of DNA, that makes up a gene. That gets read by enzymes to produce RNA, which then tells the cell to make the protein that's encoded by that gene. All of that is in our DNA sequence, and so that sounds simple enough except that we have known for a while that a large part of our genome doesn't actually code for protein that's made up of non-coding DNA. And so, that's interesting, right? How do you end up with DNA that doesn't encode a protein?
There's a few things but one thing that's also important to remember about DNA is that when it gets replicated mistakes can happen and that can introduce mutations that get passed down as cells replicate and so on. And so, while the idea of junk DNA has been around since at least the 1960s, credit for the term usually goes to a scientist named Susumu Ohno. In 1972, he wrote a paper called So Much Junk DNA in Our Genome, to talk about the fact that in a genome like ours where you have multiple copies of a gene, some of those copies might have gotten mutated to the point where they're no longer actually encoding a functional protein, and those are called pseudogenes. That's one example where you can end up with DNA that's not actually functional, but over the decades there's more evidence that our genome has a lot of DNA that's not coding anything.
And so, in 2012 there was a project called the Encyclopedia of DNA Elements or ENCODE for short, and as a result of their work they claimed that a function could be found for around 80% of our genome. That got a lot of attention from the media because it's kind of like this nice story. We have this idea of junk DNA, junk is kind of this loaded term. It now feels like it's being debunked. Actually, the story that seemed already kind of fascinating now has this new twist in it. So they were claiming this in part based on the idea that since about 80% of our genome seems to be active, like it's transcribed, something's going on, it might also be functional. That assumption ended up getting a lot of criticism because it's just a very loose idea of what function is.
And so, it's been really interesting diving into these papers about junk DNA because you can kind of sense frustration from scientists who work in this area about how junk DNA is framed. There's this one paper I read from 2014 that's called The Case for Junk DNA, and I'll just read one little bit. "It has now become something of a cliche to begin both media stories and journal articles with a simplistic claim that most or all non-coding DNA was "long dismissed as useless junk." The implication, of course, is that current research is revealing function in much of the supposed junk that was unwisely ignored as biologically uninteresting by past investigators, yet it is simply not true that potential functions for non-coding DNA were ignored until recently." I just love that, I always love when scientists are mad. I don't like it when they're mad at me, but I love it when they're mad and they're just explaining their field to people.
Sam Jones: Yeah. They're writing an opinion piece and they're out to make a point.
Deboki Chakravarti: They sure are. Because especially in academic terms, it's also so formal but you can tell. You don't always get to feel the emotion, and especially in modern academic articles, but when you do you're like this person, they care.
There are several examples that we can go through of non-coding sequences and some functions that are associated with some of them. We talked about pseudogenes already but one of the largest sources of non-coding DNA are actually called transposable elements or transposons, and these are DNA sequences that actually can jump around in your genome. Apparently up to a half of our genome might be made of transposons and some of them are known to have some kind of function but a lot of them don't apparently. We also have repeat sequences in our DNA, and so an example of one that has a very clear function are telomeres, which help maintain our chromosomes. There are also different sequences in our DNA that help to regulate the expression of genes like promoters, and silencers, and enhancers. They're all used to turn genes off, on, lower their expression, raise their expression. There's a lot going on in your DNA.
Sam Jones: So is junk DNA still a thing?
Deboki Chakravarti: Well, the fact that we found functions for these supposedly non-functional sequences may make it seem like the idea of junk DNA should be thrown out, but my sense from reading these scientists who work in this field, it seems like there is still plenty of DNA in our genome with no clear function. Really, it all gets to this fact that assigning a function to genes is actually really complicated and this conversation could go in so many directions. So for example, in one of the papers I was reading is called What We Talk About When We Talk About Junk DNA, and they're basically explaining how even the definition of function can be really different depending on who you talk to, and that can have implications for how you understand junk DNA.
So for example, there's a definition for function that's why is this gene there, and that's called the selected effect. And then, there's another definition where you're basically looking at what does the gene actually do, and that's called causal role. And the idea of junk DNA fits nicely with selected effect, the one where you're like why is the gene there when you're looking at function because you're like what is the point of it? But not necessarily as much for causal role because a sequence could do something but whether or not you think it's supposed to be doing that or not, it just gets really messy. I've seen this debate in papers get really, really granular. There's some scientists who are pushing to introduce new terms like spam DNA to talk about the way that some DNA just doesn't seem to be subject to positive selection.
Sam Jones: I really actually love that term.
Deboki Chakravarti: It's great. And even in the paper they're like ... Again, maybe the junk DNA people are just really fun to read because they are like, we know that this term may not pick up steam but we want to introduce it anyways. They're basically writing that in the paper.
Sam Jones: Right. That's great, I love that.
Deboki Chakravarti: So yeah, it's just a very long way to say scientists are still figuring it out.
Sam Jones: Thank you for diving so deep into it because I think, yeah, it's complex. Thank you, Tammy, for writing in about that because it's kind of fun too to think about.
Deboki Chakravarti: Yeah, yeah. Yeah, it's fun when you think you already have a messy narrative but you realize that actually the messy narrative is a little too clean because it's even more complicated.
Sam Jones: Yeah, fascinating.
Thanks for tuning in to Tiny Show and Tell Us, a bonus episode from Tiny Matters, a production of the American Chemical Society. To be featured in a future episode, send us an email with your Tiny show and Tell at tinymatters@acs.org, or click the Google form link in this episode's description. We'll see you next time.
- So much "junk" DNA in our genome
- No Longer Useless: The Important Roles of ‘Junk DNA’
- Scientists discover a role for ‘junk’ DNA
- Stanford Medicine-led study clarifies how ‘junk DNA’ influences gene expression
- Enhancers: five essential questions
- Transcriptional silencers: driving gene expression with the brakes on
- “Xenobot” Living Robots Can Reproduce
- Team Builds the First Living Robots
- Robots made of cells blur the line between creature and machine
- A cellular platform for the development of synthetic living machines
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