Are we close to creating all-new life forms? What are the scientific challenges? Should we be concerned about ethics?
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Brought to you by Toyota. Let's go places. Welcome to Forward Thinking. Hey there, and welcome to Forward Thinking, the podcast that looks at the future and says, in just seven days, I can make you a man. I'm Jonathan Strickland and I'm Joe McCormick. Was that a reference to the Ring? No, No, No, that was a lyric straight from Rocky Horror Picture show the Charles Atlas song in just seven days, I Can make you a man? All right, Well, it's because today we're gonna talk about making life forms synthetically, artificially, not through the old biological way, like taking all the building blocks of pieces of life and cramming them together until you get some sort of glorious Frankenstein's monster of a creation that can rampage throughout the countryside and make the peasants all scared, or a single celled organism, or okay, well we gotta we gotta crawl before we walk. Yeah, well, we've got a flagellum before we crawl, that's right. That's also a little bit of paddling through some fluid. Yeah. Yeah, So today we're gonna be talking about synthetic biology, which is a very interesting area of future research, present research, and especially future research because synthetic biology comes up all over the place when you start talking about future solutions to problems. Like one great example is we've talked about I know, we've referenced it before in the idea of colonizing other planets, like how can we make all the materials we need and you know, the food and the fuels and the medicines and stuff like that on the surface of Mars without having to carry just tons and tons of supplies and cargo along with us. And one of the solutions people are proposed is, well, what if we created organisms that we could take in tiny colony cultures with us that would multiply once we got to the planet, and then make all of these things we need, right taking the raw material that is available on Mars and converting it into the stuff that we would find useful. But of course we'd have to take a step back first and say, wait a minute, can we create organisms like that? And if we can, should we We've got a lot of questions, But first the first question we have to ask is what is synthetic biology? Because it's such a relatively new discipline, they're actually multiple definitions for it, and it depends largely upon what perspective you're taking. It's clearly related to genetic engineering. Uh, you're talking about manipulating the genes of an organism to create some sort of biological change, but it kind of goes a step beyond just that, and Uh, creating a firm definition for it is tricky, but one way to look at is take the principles behind engineering and apply them to biology. Uh. Now, there is a website synthetic biology dot org and they aid define it as the design and construction of new biological parts, devices, and systems, and the redesign of existing natural biological systems for useful purposes. And they also state that there are two different types of synthetic biologists. The first group uses quote unnatural molecules quote unnatural molecules meaning man made uh, to mimic natural molecules with the goal of creating artificial life. This would be that Frankenstein's bacterium I was just talking about. The second group uses natural molecules and assembles them into a system that acts unnaturally. This would be closer to what you were talking about, Joe, finding some sort of or creating some sort of organism that can take something that we don't find useful and turn it into something we do find useful. So, uh, you know, you can think of synthetic biology as a spectrum. On one end, you have the modification of existing biology, and on the other end of it, you have the quest to create an entirely new life form from scratch, whether it's a new maybe not a totally new life form, but maybe a specific individual within a pre existing species, but with a synthetically created genome. Yeah, and so you might be wondering, well, what does this look like in reality, Well, we don't have to speculate, because in fact, synthetic organisms already exist. Yes, they've already been created around six years old. Uh back in two thousand ten, so a little more. And in fact, just about six years ago from this week was when the scientists at the J. Craig Venter Institute, why do you why does the why does he leave the J in there? Nobody says the J the Craig Venor Institute when they announced the creation the first synthetic cell, and that this was not the first time that synthetic DNA had been put together, but this was the first time that there was an organism that began as pure information. So it's just a sequence of code inside a com pewter, which was then translated into a real live organism built out of organic chemicals and became a new living species that could survive on its own and reproduce. And we're still here. So it didn't create like the zombie apocalypse or anything. Yeah, it has it's a very slow burn. Yeah, well in reality it probably would be I think, I mean Dead season two was pretty slow. We don't have to get into that right now. The cool thing. Craig Venter himself gave a quote about this. Craig Venter, uh known, you know, big guy in genomics, you know him from the biotech field. Craig Venter said, quote, this is the first self replicating species we've had on this planet whose parent is a computer. It's a fun, quicky way of putting it. He's full of yeah. So yeah, So it was a self replicating synthetic bacterium and the team that built it, they built it out of one point eight million base pairs that went into a chromosome from the genome of a modified bacterium called Mycoplasma mi coites or miquities m y c o I d e yes mi couities. It's a strange word. It is. I've heard people say it. They all say miquities. My ability to pronounce such words is so limited that I'm I'm just going to accept whatever pronunciation you give us as the proper one. Okay, Well, there it is. Uh. And so Dr ham Smith, who is one of the leaders on the project said, quote, with the first synthetic bacterial cell and the new tools and technologies we developed to successfully complete this project, we now have the means to dissect the genetic instruction set of a bacterial cell to see and understand how it really works. So one of the things he's pointing out here is that it's not just about creating Frankenstein bacteria. It's about understanding the the understanding the building blocks of life better. By building something, you understand what it is that makes that thing work, right. Sure. Yeah, And you can see this like in in engineering again, showing the parallels to the engineering disciplines that you know, if you give someone a kit to build something, through the construction of that something, they get a better understanding of how it works. Once it's all put together. Like a radio, right, And there's a really interesting thing I'm going to talk about in a moment where the that idea comes into the very d N a of this new organism itself, the literal DNA, not the figured of DNA exactly. So, so the creation of this viable synthetic cell was a project that took a long time, tons of tons of research. It took almost fifteen years, and uh to hear Venter explained it himself and in his press release, he you know, he talked to the press about it, and he summed it up by saying, there were two major challenges they were dealing with. They'd already dealed with the sequencing the genome, so that that was a hurdle they'd already overcome going into this project. But the two maining remaining challenges. The first one was chemistry. How do you build this gigantic DNA molecule from its constituent parts. So it is a huge molecule, it's made out of lots of tiny little base pairs and it's just gigantic, and all of the base pairs have to be correct, you know, or not. A single error in some cases can cause the organism not to be viable, So you have to start with the genome of the bacterium in question. At first, what they were working with was microplasma genitalium. They changed that later for a reason I'll let you know. But uh so, they sequenced this genetic information and then they had this digital information that's spelled the recipe for the organism's DNA. But how do you turn that into a physical chromosome that goes into a cell. The second major challenge was essentially surgery. Once you've got a synthetic chromosome, how do you transplant it into a living cell and have that cell be viable and self reproducing. Uh So, for example, they discovered that one host cell they were trying to transplant this foreign chromosome into was it was full of nuclease that was defensively destroying the foreign d NA when it was introduced. In inventor's words, it would just eat up are synthetic chromosome. So I mean, good good on that cell. Right, Yeah, I was doing what it was supposed to do. Yeah, it doesn't want to be a synthetic organism. Right, It's like when you're being attacked by a virus um. So this is interesting. So the first challenge being, well, you're just creating the synthetic chromosome in the first place, and then once you have that, you still have the challenge of how do you introduce this into a living because otherwise you just got data but no computer to run it on. Essentially, if you want to have a comparison to to our our technology, so you have to insert that that software into a computer. In this case, it's a computer that already has its own software and that software wants to kill the new software. Yeah. Uh So once they got all that figured out that, the way eventually they went about the US was they built the synthetic DNA chromosome inside a yeast cell and then removed it from the yeast and they had to methylate it in order because they discovered that methylation protects the DNA from being digested by the host bacterium and then transplant it into a shell bacterium or a host bacterial cell. In these cases it was microplasma capriculum. So another problem they encountered along the way they talked about was that the cell wouldn't grow fast enough they were trying to do this, and so they ended up uh starting with the genome of a different organism. After microplasma genitalium didn't work well enough, they went with microplasma micodes and this organism had a much larger chromosome. It's bigger, harder to work with at over one million base pairs. Another thing that's really cool that they did is they put water marks in the d NA to leave no room for doubt as to whether the DNA was synthetic or natural. And what these were were stretches of non coding DNA, which DNA that doesn't actually make any proteins. You could just think of it as kind of metadata or the you know, slash slash notes sections in a piece of computer code. Uh. And these were used to code in written messages in the organism's DNA, including names of the authors on the research a web address associated with the project project so Ventor said, you know, if you can decode this, you can email us. Yeah. Three three quotes. They put some quotes in there. So one was a James Joyce quote, this is great to live, to air, to fall, to triumph, and to recreate life out of life. Good quote. A second one was from the book American Prometheus, which was about Robert Oppenheimer, and the quote was see things not as they are, but as they might be. That's a good one too, not not a bad open higher quote. I could think of one that would have been worse. Yeah, I have become death. The third was, of course from Richard Feynman, when Speineman said what I cannot build, I cannot understand. And that's the quote that I was referring to earlier. Right, I'm very sad that they didn't include the Frankenstein quote fire bad. But maybe maybe if we decode the that email address right when I can write when I make my synthetic bacterium, that's definitely going in there, you know. Listening to Ventor explain all of the different problems they encountered and fixes that they had to go through to to finally arrive at this research success, it is amazing that they were able to do this. I want to read one particular paragraph from Ventor's presentation from May two thousand ten about this, because I found this part really fascinating. It was about how the team had to develop debugging software to debug the organism because you know, they were they were creating a synthetic chromosome, so here's how it goes. So the team developed a new debugging software where we could test each synthetic fragment to see if it would grow in a background of wild type DNA, and we found that ten out of the eleven one hundred thousand base pair pieces we synthesized were completely accurate and compatible with a life forming sequence. We narrowed it down to one fragment, we sequenced it and found just one base pair had been deleted in an essential gene So accuracy is essential. There are parts of the genome where it cannot tolerate even a single error, and then there's parts of the genome where we can put in large blocks of DNA as we did with the water marks, and it can tolerate all kinds of errors. So it took about three months to find that error and repair it. And then one early morning at six am, we got a text from Dan saying, now the first blue colonies existed, and that's referring to you know that these things were reproducing within within a couple of days. I think they were. There were enough of them that you could physically see them in the Petrie dish. Wow, that's pretty impressive. I love this that they had to create a debugging program for the organism. Yeah, you imagine like that. That's a whole new discipline of quality assurance having to go through and because I you know, we know people who do q A for a living. They have to go through and test every single element of code. This is in fact biological code. It is exactly the the it's in line. I won't say it's exactly the same thing, but it's in line with that same sort of discipline. It's also absolutely what they had in Jurassic Park. Yes, using virtual reality and mr DNA. Uh So. Another thing that I just wanted to emphasize. I know I've already said it, but I just find so fascinating about this and what it illuminates about the nature of life is how zilient the DNA code is in some ways and how fragile it is in other ways. A missing a missing or deleted base pair in one section of the code can completely make you a non viable organism, but other parts you can just do all kinds of crazy stuff with. Well, again, I think if you if you compare that to the idea of software like there are there are errors you can make when you're coding something in software, and it might make something unusual happen when you're trying to execute the software. But there are other errors you can make that can make that software completely unstable, and it will won't even run problem, not only crash, but crash your entire system. Right, I'm thinking about every video game that's been released over the last twelve months. But maybe that's just because of a little bitter about bug game destroying bugs released on day one. I don't really know which one is you're referring to the pretty much yeah anyway, well but but but but I'm saying that the similarity really is there, and as much as I'm making fun of of of something that's running rampant through the video game industry, the idea being that, uh, when you start to think about d n A is being similar to software, at least in a in a general sense, then you're like, oh, yeah, I get it. Because some errors in encoding are not that huge a deal. You might be able to pick up on it, uh if something unusual happens while you're executing the code, and others are absolutely deal breakers. Yeah, but anyway, I I think this is so cool that you can chart how they went from information to chemistry to biology, like there was the entire pathway from just from idea to life. And so this first synthetic cel was called micro plasma MI codes j C v I for j Craig vinor institute sin one point, oh, not sin like like doing evil and synthetic. Yeah, so in one point. Oh what does it mean? Well, it helps us understand better the chemical basis of life. That's one big thing where we you know, learn a lot about about chromosomes and DNA and the role different genes play than we can do continuing research. Now that we have the basis for creating synthetic organisms. Uh, it might be useful in synthesizing germs that cause diseases so those diseases can be treated and overcome. Uh, it might be useful for creating synthetic biological organisms like we were talking about earlier. So you know, if you want to make some algae that could remediate waste products or capture CEO two, or create biofuels or food or or whatever. Yes, so these are uh, you know, basic ideas well where you visit that towards the end of the episode two, when we start talking about the the various things you can do with the discipline of synthetic biology. This is a pretty important part of that. Yeah, an amazing first step. Yeah. So the interesting thing is that's not where the story ends. That was, but we have continued the advancement of synthetic biology since then. Yeah, an inventor and his team specifically have. After they created SIN one point. Oh, they set out with a new goal to design a bacterium with the absolute minimum GENO. And why would you want to do that? Well, they wanted to figure out what bits of code are essential and what are not essential. Yeah, and this is this is really smart to do, I think, because we had this problem last time, right where some parts of code it seems like it don't matter. You can change them with no no big impact. Other parts can our our game breakers. Well, and we've also found that there are segments of DNA within different organisms that ultimately originated from other species and don't have any useful uh you know, useful performance, or they don't do anything, or it's a duplicate of something else that already works perfectly. Right, So maybe we can make life better more efficient, cut out the fat and and Furthermore, Yeah, just just what you were talking about, Joe, just figure out exactly what the different pieces do, because because even though we've we've sequenced plenty of genomes, we really don't understand very well what all of the individual genes do and and specifically how they work together in the genome. That's that's way beyond us right now. Um but this can help us learn hypothetically. I mean, their first attempts totally failed, so uh and and and no one was more surprised than Ventor. He there's a great quote where he was like, I was shocked, Like, well, you know, I love you, I love the idea. We gotta remember you learn more through failure than you do through success. Completely that that is literally how science works. Um So, ideally you can learn from other people's failures in your own successes. That way you look like you are awesome, right, much preferable. But yeah, okay, So the first attempt that they made, two different teams each independently tried to build a bacterium from the ground up, and it was just it was too ambitious given our current aforementioned lack of knowledge about genetics and genomics. Um So, to give you like a metaphor here additive manufacturing a genome didn't work. But but what about whittling something down? What about removing all the parts of the genome that are not the statue of David gotcha? All right? So so the traditional subtractive approach where you you are taking away everything that is not necessary for whatever the finished product needs to be. So so they took SIN one point oh and they started labeling all of its pieces. They took its nine one genes and played with deleting or disrupting different sections in turn. And when they plugged the resulting experiments into a m capric column, it did, you know, either be viable or totally not viable? And if if it died, if it was not viable, they knew that they had removed something important science. This this makes me think of what early medicine must have been, like, yeah, it turns out you needed that one. It reminds me of that moment where Bones is, you know, in the twentieth century, and he's like these savages. But but eventually it produced what they call SIN two point oh, which was the first micro but with a genome smaller than the world's smallest known natural genome, which is microplasma genitalium, which has only five UM. And then along came SIN three point oh, which is a living, reproducing organism with just four hundred and seventy three genes. They trimmed out all of those non essential or a lot of those not essential and duplicate genes. Um. But but even at this point the critter still might contain some some coding. Blow to the researchers are not sure what a hundred and forty nine of those genes do. I do like the idea that they can cut out a whole bunch of genes and pass the savings onto you. I think that's that's very forward thinking. Other than other than those amazing savings, Um, why would you want to do this? Uh? Well, this resulting organism SIN three point oh can be used to study what specific genes do, both the ones that it currently possesses and also all of the bits that they removed from versions one and two in order to make three. By by adding them back in one at a time, they can watch the results play out. And furthermore, uh, the SIN three point oh grows like and reproduces really fast. So uh SIN three point o cell populations double in about three hours. So that's a great laboratory tool. And and eventually they're hoping to create a living organism for which the entire genome is understood. And I cannot stress how rad that would be. I mean, I mean, even if you're only talking about the world's very biddiest genomic code, uh, because you know, like I said, like just because we can, we can sequence the whole genome, even very much more complex genomes. Humans for example, have some thousand genes. Uh that that absolutely doesn't mean that we know what what all of that coding does. It would be a really huge, really huge mile marker. And I think what's really cool here also is by adding in those genes one at a time and seeing what they do. It's not even as simple as that, because genes can interact with one another. So sometimes it may be that you let's say that you've got one version of this artificial life form and you add in one gene and you see how that that works. You've got a different version of that same artificial life form that has a slightly different series of genes in it. It may not have exactly the same as the first one. You add that same gene into that one, and you see that it expresses itself in a different way. That tells you there's going to be sort of interaction going on. It also displays, yeah, we there's so much we don't know. And it's once you start looking at these numbers, like even just with a few hundred, it's complicated. When you get to several, you know, tens of thousands, it gets really really tough. So let's take a look at maybe something that might be a touch more ambitious, creating the first artificial human cell. Yeah, so in May, we are recording this. At the end of May, about one fifty genetics experts met at Harvard to talk about the possibility of building an entire human genome, not altering one, not sequencing one, but building one. And the project is called h g P right w R I T E. Testing Large synthetic genomes and cells and h g P stands for the Human Genome Project. So this approach would require you to have access to a DNA synthesizer computer and the raw materials, cop cars, some sunglasses. I'm sorry, I think about the Blues Brothers, DNA synthesizer, computer and raw materials. Where what you would need. Basically, they would build the entire genome from the ground up, and the next step would be to insert that synthetic genome into a human cell, kind of like what you were talking about, Joe, just to see if it could replace the already existing DNA within the human cell. Boot that all the way and kind of reboot the cell so that it now is the synthetic one. Uh So it's talking about really programming a new type of human cell. You you program a human in the sense that you're the one who determines the DNA sequence from beginning to end. And Dr J. Keisling of the University of California, Berkeley is part of a group putting together a standardized or putting together a database of standardized DNA chunks, and they're calling these chunks bio bricks. This is actually an idea that I think dates back to about two thousand six. But uh these these bio bricks represent specific stretches of genetic material, and assembling the full genome involves putting these chunks together kind of like a big puzzle, like a like a Lego but yeah, squishy human person at the end. I think Lego is even better. Than than puzzle. Definitely. Yeah. It's like like you've got the lego blocks and your your bio bricks, like, oh, here's here's one that is this particular gene, and then we need to have this other one, this other connective piece here before we put this other gene in. Otherwise it's not all going to fall apart. It definitely don't spill them on the floor because those hurt like a mother. Yeah, you step on a bio brick and it's gonna be squishy and it's gonna go right into the heel. So they're they're meant to be interchangeable parts. Uh. And you could build biological systems living within a cell and you can arrange them to make quote unquote useful devices, which is I thought a really interesting way of putting it, Like you can use bio bricks to create useful to vices. You're really talking about biological elements, and it's weird to think of a biological element as a device, but it does show again how engineering and biology are very commingled in this approach. And I mean technically, like our hands are devices. I guess, I guess I you know, I mean, I I very rarely think of anything that is part of me as a device. And I mean, I realize I'm almost physically attached to my phone all the time, but I don't. I still don't think of it as part of me. I don't pick it up and say, at last, my arm is complete again. But then you have a group called bio Bricks Foundation, and that builds itself as quote a bio biotechnology in the public interest and the purpose of this organization has developed the tools and processes of synthetic biology in a responsible manner. So it's supposed to be uh concerned with ethics, with the cost of this, with the access of it, so that people can learn from the research that they do and us apply it to their own research. And they also want to make sure that they limit the spread of mad scientists, you know, keep that to a bare minimum, uh or at the very least of shortsighted projects that might have bigger ethical problems down the line that you might not have anticipated just because you were focused on the first stage and not thinking, oh, what are the implications of this. One of the founders of the bio Bricks Foundation is Dr Drew Inde E. N d Y, who played a role in developing the bio brick standard part technology, so the legos. In other words, he played a role in developing those And interestingly, he actually declined to participate in that project I was talking about with the hundred fifty researchers at Harvard. He said he wasn't going to go because he was concerned that perhaps they were rushing ahead toward a goal without really contemplating the ethical consequence system. Yeah, like, maybe maybe start with a goldfish first, you guys, like, do we really need to move straight to human And you know, we've talked about this on previous episodes, where if you set yourself a specific goal, it hones you in, It focuses you so that you can really take the steps necessary to solve some big problems that ultimately can end up benefiting you in other ways and other applications. But it helps to have that goal there, to have something to work toward. But he still felt that perhaps this was a little too grandiose and idea with too few actual um uh thought given or too little thought given to the ethical implications. Now, when can we expect this to happen? Assuming it it goes forward, We don't know they're talking about a ten year time frame, but that seems incredibly ambitious. For one thing, this project is not funded yet, and for another, it's really difficult to say how hard it would be to actually synthesize a full human genome um, and because that genomes five thousand times larger than that bacterium we talked about earlier, the sin one point. Oh, it's gonna be expensive, though less so than it would have been a decade ago. In two thousand three, it cost four dollars to sequence an individual letter in the genome. Now it's closer to three cents. So the money, the cost side of it is falling dramatically, but still, if you want to sequence the human genome, that's a three billion letters total, so that the cost about ninety million dollars. It's a lot of money. Um. If we continue to drive down the cost, then obviously genome synthesis could get closer to a more affordable amount. One estimation is that in twenty years you could get down to about a hundred thousand dollars, which could be something that a major scientific research project could actually do. But that's twenty years, and that's that's ten years beyond what the ten year uh span of the project was proposed to be um so, I don't know if this is actually gonna go anywhere. It may end up being that that people like Dr Indy are able to say, hey, let's before we jump into this project, let's have a deeper conversation about the implications of this and make sure we truly understand what we are doing, and that if we choose to go forward, we do so in a responsible manner right, because the potential upsides of this are really incredible. Yes, I mean, I I think the sky level hope for any kind of genetic study is is that we will be able to design bits of code to replace genetic code that's causing deadly, terrible and curable diseases and suffering in people. Um Or to to to make our food sources grow better, faster, stronger, and more nutritious and maybe vegan and in difficult conditions and all that kind of thing. Um Or I don't know, to make house cats that do care about us at all, or tall order giraffes with built in rollerblade. I don't know what people get up to, but yeah, I mean, you know, everyone's got a hobby, so I agree. I think that that is definitely the the ideal goal of this. You know, it's not too it's not too welcome. This is human version two point. Oh, we've built a right, It's that's that's not what people are going for necessarily. Crab claws and clamps with you, Joe, Yeah, they're the best. Yeah. Well, well, I mean we learned I didn't really learn anything about Joe. We just had something kind of reinforced a belief that we had already discovered earlier. I mean, hold on, do you guys go out of your way to mess with a crab? No? You don't. No. I mean, if there's a crab in my way, I'll go ahead and mess with it. But I don't go out of my way to mess with a crab. I really only mess with them when I'm trying to consume their delicious flesh and mostly toss them aside now just out of fear, all right, at any rate. That so that's that's the big big picture. Like if we can figure it out, maybe we can defeat lots of genetically uh or lots of diseases that are genetically based, more conditions or things like that, perhaps extending lifespans, things of that nature. That's that's like the gold standard a goal that we have, but there are other ones as well, right, Yeah, And most of it is kind of along the lines of what Joe you were talking about earlier and what we have talked about previously on this show about genetically engineering bacteria to produce useful stuff like biofuel or or bacteria that eat explosives and can thus be used to dismantle landmines. By building an entire genome, we can hypothetically make very very efficient bacteria that do those sorts of things. And for example, Dr Kisling of the bio Brick Project worked on this one proof of concept project in the early aughts in which a team created Equali bacteria that produce an anti malaria drug. And the yield from these bacteria is so much more efficient than from the traditional method of growing and harvesting sweet wormwood, which is how you usually get the drug component. Um, it's like a million times more efficient than doing that, so the price of the drug dropped. Everybody wins. That's super awesome. Yeah, And I was reading that synthetic biology has already led to the development of diagnostic tools for lots of different diseases, including things like hepatitis and HIV. So there are a lot of different potential applications for synthetic biology in the medical field. Not a big surprise. I mean, it makes sense that that would be a place where we would really focus that. But there's the possibility that synthetic biology will play a role in lots of other different things, like, for example, biologically based computational systems. I mean, there's there's the possibility for that too. I mean, we could we could engineer biologically engineer an organic computer, and that is so science fiction that it makes my head spin a little bit. Yeah, and there's research teams out there that are working on coding data in d n A s Yeah exactly. Yeah. Uh and and and along those lines, you've also, of course got the thing that we always like talking about on this show, which is the pure research angle. You sure, these lines of inquiry will help us figure out what genes do and how they interact with each other, and that is so worthwhile, right, And I think I think to the general public, it's news that we don't understand all of this yet, because exactly right, once we got to the point of the sequencing of the human genome. Everyone said, oh, so we we now know what everything does and you have to explain. No, what we found was the complete text of what we are, but we don't understand the language it's written in yet, not fully. And we don't know how this passage fourteen chapters down actually depends heavily on something that's written in chapter two and something else has written in chapter thirty seven. Like that makes it super hard for you to be able to interpret that. Yeah, so figuring that out it would would be nifty Yes, I agree, I agree. Okay, so, so we've covered the wonder and and the potentials of the future. Guys, let's get into some dubin gloom. Okay, what could go wrong? Well, you know, this is what Dr Indy was concerned about, right, the idea of let's think about the consequences of research to make sure that we're doing doing any sort of research in the most responsible way possible. So, one possibility, although it's definitely in the realm of like more of the Stephen King horror story approach, is that someone develops a synthetic life form that ends up not being contained within the lab and that ends up encountering the rold at large and perhaps starts to replicate itself. This could be on the you know, single cell level. It doesn't necessarily have to be Frankenstein's Monster like I keep joking about, or a zombie apocalypse. I'm but but it could certainly disrupt an ecosystem, right, right, Yeah, So if for example, it doesn't even have to be like a pathogen that attacks humans, right, It could merely be invasive. It could just be a very very successful organism that outcompetes everything that naturally lives around it. Right, And then we end up seeing uh, decrease in biodiversity, We see various species uh end up fighting so that they don't go extinct. Uh, it ends up creating big issues. So there's that one um and you know, if it were to turn into a pathogen, that would obviously be even worse. But it doesn't have to for it to have negative consequences in our world. There's also the question going beyond like that that approach, who owns the life form? This is a whole new area of science. And does it mean that you would be able to protect a an engineered life form like using intellectual property approach like you would software would you copyright a life form. You're not supposed to be able to do that right now, but maybe the rules need to change if we're talking about a purely synthetic creature designed from the ground up. So somebody if they find this organism dwelling on your skin or in your hair or something like that, they can file a d m c A claim against you, right or or you could end up suing the company that made the thing and say you have not been very careful with your containment procedures, because I've got it on me now. So, I mean, it's a weird thing that fortunately you put all these uh these copyright clauses into its d n A, so I know where it came from, right, Look, you signed the service agreement as soon as that bacteria made contact with your skin. Uh yeah, this is I mean, it's we're joking about it, but it really is the question of who owns that, Like, does the person who made the technology own it? Does the person who actually sequenced there are created synthesized rather the genes in that sequence? Did they own it? Is ownership not even a thing. We don't have the answers to that. And then of course they're just the big ethical concerns. Is it all right? Is it? Is it? Is it ethical to design a life form, just any life form, let alone a human? And if it is, then is there a is there a line like? Is there a point where we say before this it's it's totally cool. But after this we have to start asking ourselves some questions. Yeah, how many cells does an organism have to have before we start to be worried about it? Right? Ken? Is it? Is it all right to engineer bacteria so that we can do lots of medical research and potentially cure diseases? I think most people would say, yeah, that sounds like that would be all right or all right? Is it okay to genetically design assuming we ever got this capability, which is a big assumption, But it was okay to genetically design an animal so that it most most closely resembles a pet that you used to have? Is that okay? Is it okay to design a human being so that the human being has as many positive attributes and as few negative attributes according to some given persons? Yeah, according to to the designer, is gatica, okay? Is what I'm getting at is gantica? Okay? Not Galagha, which is awesome, but Gantica. Uh. I mean, these are these are big questions. And again that's the source of stuff that dr Indy was asking. He was saying, you know, we need to consider this. Maybe we need to ask the should we question before we ask the could we question. That's you know, Patton Oswald's like always asking the kudah, never asking the shouda. He's saying, we should ask the shuldah. Let's do that, guys, And um, I can't disagree with that. I think that's I think that's the responsible thing to do. But then I'm I'm a liberal arts major, not a not a super scientist like the folks over at at that Harvard meeting where so really interesting. Do you guys have any other thoughts about synthetic biology before we sign off? It's okay to say no, I think you've spoken all my thoughts for me. That's fair. It's also really hot in here at this at this juncture. I have thoughts about snacks. Yeah, I have thoughts about air conditioning. Let's wrap this up. So, guys, if you have suggestions for future episodes of forward thinking, you want to know how something's gonna you know what it's gonna be like in the future, or you've got comments or thoughts about any of the episodes we've done in the past. Maybe you want us to do an update to an old episode where we've got more information now that we're further into the future than we were when we started. Let us know. 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