WEBVTT - Manufacturing Lifeforms 0:00:00.160 --> 0:00:07.160 Brought to you by Toyota. Let's go places. Welcome to 0:00:07.360 --> 0:00:14.560 Forward Thinking. Hey there, and welcome to Forward Thinking, the 0:00:14.720 --> 0:00:17.319 podcast that looks at the future and says, in just 0:00:17.600 --> 0:00:20.640 seven days, I can make you a man. I'm Jonathan 0:00:20.680 --> 0:00:25.720 Strickland and I'm Joe McCormick. Was that a reference to 0:00:25.800 --> 0:00:31.320 the Ring? No, No, No, that was a lyric straight 0:00:31.400 --> 0:00:37.239 from Rocky Horror Picture show the Charles Atlas song in 0:00:37.320 --> 0:00:40.080 just seven days, I Can make you a man? All right, Well, 0:00:40.080 --> 0:00:46.159 it's because today we're gonna talk about making life forms synthetically, artificially, 0:00:46.840 --> 0:00:50.879 not through the old biological way, like taking all the 0:00:50.920 --> 0:00:54.600 building blocks of pieces of life and cramming them together 0:00:54.760 --> 0:00:58.840 until you get some sort of glorious Frankenstein's monster of 0:00:58.880 --> 0:01:02.320 a creation that can rampage throughout the countryside and make 0:01:02.360 --> 0:01:06.160 the peasants all scared, or a single celled organism, or okay, 0:01:06.160 --> 0:01:09.320 well we gotta we gotta crawl before we walk. Yeah, well, 0:01:09.360 --> 0:01:12.360 we've got a flagellum before we crawl, that's right. That's 0:01:12.360 --> 0:01:15.880 also a little bit of paddling through some fluid. Yeah. Yeah, 0:01:15.959 --> 0:01:18.920 So today we're gonna be talking about synthetic biology, which 0:01:18.959 --> 0:01:23.320 is a very interesting area of future research, present research, 0:01:23.360 --> 0:01:27.319 and especially future research because synthetic biology comes up all 0:01:27.400 --> 0:01:30.800 over the place when you start talking about future solutions 0:01:30.840 --> 0:01:34.640 to problems. Like one great example is we've talked about 0:01:34.800 --> 0:01:37.760 I know, we've referenced it before in the idea of 0:01:37.800 --> 0:01:40.920 colonizing other planets, like how can we make all the 0:01:41.000 --> 0:01:43.840 materials we need and you know, the food and the 0:01:43.880 --> 0:01:47.240 fuels and the medicines and stuff like that on the 0:01:47.280 --> 0:01:49.840 surface of Mars without having to carry just tons and 0:01:49.880 --> 0:01:52.440 tons of supplies and cargo along with us. And one 0:01:52.440 --> 0:01:54.920 of the solutions people are proposed is, well, what if 0:01:54.960 --> 0:01:58.600 we created organisms that we could take in tiny colony 0:01:58.640 --> 0:02:01.440 cultures with us that would multiply once we got to 0:02:01.480 --> 0:02:04.320 the planet, and then make all of these things we need, 0:02:04.560 --> 0:02:07.600 right taking the raw material that is available on Mars 0:02:07.640 --> 0:02:10.400 and converting it into the stuff that we would find useful. 0:02:10.880 --> 0:02:12.960 But of course we'd have to take a step back 0:02:13.000 --> 0:02:17.040 first and say, wait a minute, can we create organisms 0:02:17.080 --> 0:02:20.280 like that? And if we can, should we We've got 0:02:20.280 --> 0:02:22.920 a lot of questions, But first the first question we 0:02:22.960 --> 0:02:25.560 have to ask is what is synthetic biology? Because it's 0:02:25.560 --> 0:02:30.920 such a relatively new discipline, they're actually multiple definitions for it, 0:02:31.000 --> 0:02:34.919 and it depends largely upon what perspective you're taking. It's 0:02:34.919 --> 0:02:39.000 clearly related to genetic engineering. Uh, you're talking about manipulating 0:02:39.040 --> 0:02:40.720 the genes of an organism to create some sort of 0:02:40.720 --> 0:02:43.880 biological change, but it kind of goes a step beyond 0:02:44.120 --> 0:02:48.160 just that, and Uh, creating a firm definition for it 0:02:48.200 --> 0:02:51.040 is tricky, but one way to look at is take 0:02:51.080 --> 0:02:55.720 the principles behind engineering and apply them to biology. Uh. Now, 0:02:55.760 --> 0:02:59.959 there is a website synthetic biology dot org and they 0:03:00.000 --> 0:03:02.880 aid define it as the design and construction of new 0:03:02.960 --> 0:03:08.840 biological parts, devices, and systems, and the redesign of existing 0:03:09.080 --> 0:03:12.519 natural biological systems for useful purposes. And they also state 0:03:12.560 --> 0:03:15.160 that there are two different types of synthetic biologists. The 0:03:15.240 --> 0:03:22.799 first group uses quote unnatural molecules quote unnatural molecules meaning 0:03:22.880 --> 0:03:26.280 man made uh, to mimic natural molecules with the goal 0:03:26.320 --> 0:03:30.079 of creating artificial life. This would be that Frankenstein's bacterium 0:03:30.080 --> 0:03:33.000 I was just talking about. The second group uses natural 0:03:33.040 --> 0:03:36.680 molecules and assembles them into a system that acts unnaturally. 0:03:36.800 --> 0:03:38.880 This would be closer to what you were talking about, Joe, 0:03:38.960 --> 0:03:42.840 finding some sort of or creating some sort of organism 0:03:42.960 --> 0:03:46.160 that can take something that we don't find useful and 0:03:46.160 --> 0:03:50.720 turn it into something we do find useful. So, uh, 0:03:50.800 --> 0:03:53.800 you know, you can think of synthetic biology as a spectrum. 0:03:54.360 --> 0:03:57.080 On one end, you have the modification of existing biology, 0:03:57.160 --> 0:03:58.400 and on the other end of it, you have the 0:03:58.440 --> 0:04:01.520 quest to create an entirely new life form from scratch, 0:04:01.800 --> 0:04:04.800 whether it's a new maybe not a totally new life form, 0:04:04.840 --> 0:04:08.680 but maybe a specific individual within a pre existing species, 0:04:09.040 --> 0:04:12.680 but with a synthetically created genome. Yeah, and so you 0:04:12.800 --> 0:04:16.240 might be wondering, well, what does this look like in reality, Well, 0:04:16.240 --> 0:04:20.520 we don't have to speculate, because in fact, synthetic organisms 0:04:20.520 --> 0:04:24.839 already exist. Yes, they've already been created around six years old. 0:04:26.720 --> 0:04:30.000 Uh back in two thousand ten, so a little more. 0:04:30.040 --> 0:04:33.640 And in fact, just about six years ago from this 0:04:33.680 --> 0:04:38.680 week was when the scientists at the J. Craig Venter Institute, 0:04:38.720 --> 0:04:40.320 why do you why does the why does he leave 0:04:40.360 --> 0:04:42.480 the J in there? Nobody says the J the Craig 0:04:42.600 --> 0:04:48.039 Venor Institute when they announced the creation the first synthetic cell, 0:04:48.240 --> 0:04:50.440 and that this was not the first time that synthetic 0:04:50.520 --> 0:04:53.160 DNA had been put together, but this was the first 0:04:53.200 --> 0:04:57.520 time that there was an organism that began as pure information. 0:04:57.600 --> 0:05:00.320 So it's just a sequence of code inside a com pewter, 0:05:00.800 --> 0:05:05.440 which was then translated into a real live organism built 0:05:05.440 --> 0:05:09.120 out of organic chemicals and became a new living species 0:05:09.160 --> 0:05:12.120 that could survive on its own and reproduce. And we're 0:05:12.120 --> 0:05:15.600 still here. So it didn't create like the zombie apocalypse 0:05:15.720 --> 0:05:19.359 or anything. Yeah, it has it's a very slow burn. Yeah, 0:05:19.839 --> 0:05:22.400 well in reality it probably would be I think, I 0:05:22.400 --> 0:05:25.880 mean Dead season two was pretty slow. We don't have 0:05:25.920 --> 0:05:28.159 to get into that right now. The cool thing. Craig 0:05:28.240 --> 0:05:31.720 Venter himself gave a quote about this. Craig Venter, uh known, 0:05:31.839 --> 0:05:35.160 you know, big guy in genomics, you know him from 0:05:35.200 --> 0:05:38.440 the biotech field. Craig Venter said, quote, this is the 0:05:38.480 --> 0:05:41.760 first self replicating species we've had on this planet whose 0:05:41.760 --> 0:05:45.560 parent is a computer. It's a fun, quicky way of 0:05:45.600 --> 0:05:49.400 putting it. He's full of yeah. So yeah, So it 0:05:49.480 --> 0:05:53.159 was a self replicating synthetic bacterium and the team that 0:05:53.200 --> 0:05:55.760 built it, they built it out of one point eight 0:05:55.800 --> 0:05:59.880 million base pairs that went into a chromosome from the 0:06:00.000 --> 0:06:04.520 genome of a modified bacterium called Mycoplasma mi coites or 0:06:04.760 --> 0:06:08.680 miquities m y c o I d e yes mi couities. 0:06:10.400 --> 0:06:12.919 It's a strange word. It is. I've heard people say it. 0:06:12.960 --> 0:06:16.520 They all say miquities. My ability to pronounce such words 0:06:16.640 --> 0:06:19.520 is so limited that I'm I'm just going to accept 0:06:19.600 --> 0:06:23.039 whatever pronunciation you give us as the proper one. Okay, Well, 0:06:23.080 --> 0:06:25.720 there it is. Uh. And so Dr ham Smith, who 0:06:25.720 --> 0:06:27.800 is one of the leaders on the project said, quote, 0:06:28.000 --> 0:06:31.279 with the first synthetic bacterial cell and the new tools 0:06:31.279 --> 0:06:34.800 and technologies we developed to successfully complete this project, we 0:06:34.880 --> 0:06:39.159 now have the means to dissect the genetic instruction set 0:06:39.200 --> 0:06:42.599 of a bacterial cell to see and understand how it 0:06:42.680 --> 0:06:44.599 really works. So one of the things he's pointing out 0:06:44.600 --> 0:06:48.440 here is that it's not just about creating Frankenstein bacteria. 0:06:48.560 --> 0:06:52.880 It's about understanding the the understanding the building blocks of 0:06:52.920 --> 0:06:56.640 life better. By building something, you understand what it is 0:06:56.720 --> 0:07:00.760 that makes that thing work, right. Sure. Yeah, And you 0:07:00.800 --> 0:07:04.800 can see this like in in engineering again, showing the 0:07:04.920 --> 0:07:08.400 parallels to the engineering disciplines that you know, if you 0:07:08.520 --> 0:07:13.040 give someone a kit to build something, through the construction 0:07:13.240 --> 0:07:15.800 of that something, they get a better understanding of how 0:07:15.880 --> 0:07:18.800 it works. Once it's all put together. Like a radio, right, 0:07:18.880 --> 0:07:21.040 And there's a really interesting thing I'm going to talk 0:07:21.040 --> 0:07:24.000 about in a moment where the that idea comes into 0:07:24.040 --> 0:07:27.440 the very d N a of this new organism itself, 0:07:28.040 --> 0:07:31.200 the literal DNA, not the figured of DNA exactly. So, 0:07:31.200 --> 0:07:33.960 so the creation of this viable synthetic cell was a 0:07:33.960 --> 0:07:36.960 project that took a long time, tons of tons of research. 0:07:37.000 --> 0:07:40.240 It took almost fifteen years, and uh to hear Venter 0:07:40.360 --> 0:07:42.920 explained it himself and in his press release, he you know, 0:07:42.960 --> 0:07:45.200 he talked to the press about it, and he summed 0:07:45.200 --> 0:07:47.320 it up by saying, there were two major challenges they 0:07:47.320 --> 0:07:50.640 were dealing with. They'd already dealed with the sequencing the genome, 0:07:50.760 --> 0:07:53.400 so that that was a hurdle they'd already overcome going 0:07:53.440 --> 0:07:57.000 into this project. But the two maining remaining challenges. The 0:07:57.000 --> 0:08:01.360 first one was chemistry. How do you build this gigantic 0:08:01.480 --> 0:08:06.000 DNA molecule from its constituent parts. So it is a 0:08:06.080 --> 0:08:08.640 huge molecule, it's made out of lots of tiny little 0:08:08.640 --> 0:08:12.640 base pairs and it's just gigantic, and all of the 0:08:12.640 --> 0:08:15.200 base pairs have to be correct, you know, or not. 0:08:15.960 --> 0:08:19.200 A single error in some cases can cause the organism 0:08:19.200 --> 0:08:23.280 not to be viable, So you have to start with 0:08:23.320 --> 0:08:26.760 the genome of the bacterium in question. At first, what 0:08:26.840 --> 0:08:30.160 they were working with was microplasma genitalium. They changed that 0:08:30.280 --> 0:08:33.160 later for a reason I'll let you know. But uh so, 0:08:33.200 --> 0:08:36.720 they sequenced this genetic information and then they had this 0:08:36.840 --> 0:08:40.520 digital information that's spelled the recipe for the organism's DNA. 0:08:40.640 --> 0:08:44.239 But how do you turn that into a physical chromosome 0:08:44.360 --> 0:08:47.760 that goes into a cell. The second major challenge was 0:08:47.840 --> 0:08:51.600 essentially surgery. Once you've got a synthetic chromosome, how do 0:08:51.679 --> 0:08:55.360 you transplant it into a living cell and have that 0:08:55.360 --> 0:08:59.720 cell be viable and self reproducing. Uh So, for example, 0:08:59.760 --> 0:09:02.000 they discovered that one host cell they were trying to 0:09:02.040 --> 0:09:05.960 transplant this foreign chromosome into was it was full of 0:09:06.040 --> 0:09:09.760 nuclease that was defensively destroying the foreign d NA when 0:09:09.760 --> 0:09:12.560 it was introduced. In inventor's words, it would just eat 0:09:12.640 --> 0:09:15.840 up are synthetic chromosome. So I mean, good good on 0:09:15.880 --> 0:09:17.760 that cell. Right, Yeah, I was doing what it was 0:09:17.800 --> 0:09:20.520 supposed to do. Yeah, it doesn't want to be a 0:09:20.559 --> 0:09:23.520 synthetic organism. Right, It's like when you're being attacked by 0:09:23.520 --> 0:09:26.160 a virus um. So this is interesting. So the first 0:09:26.240 --> 0:09:29.079 challenge being, well, you're just creating the synthetic chromosome in 0:09:29.120 --> 0:09:32.000 the first place, and then once you have that, you 0:09:32.040 --> 0:09:34.280 still have the challenge of how do you introduce this 0:09:34.400 --> 0:09:37.400 into a living because otherwise you just got data but 0:09:37.480 --> 0:09:39.920 no computer to run it on. Essentially, if you want 0:09:39.920 --> 0:09:43.960 to have a comparison to to our our technology, so 0:09:44.040 --> 0:09:46.840 you have to insert that that software into a computer. 0:09:46.920 --> 0:09:49.240 In this case, it's a computer that already has its 0:09:49.240 --> 0:09:53.560 own software and that software wants to kill the new software. Yeah. 0:09:56.000 --> 0:09:58.079 Uh So once they got all that figured out that, 0:09:58.160 --> 0:10:00.400 the way eventually they went about the US was they 0:10:00.400 --> 0:10:04.760 built the synthetic DNA chromosome inside a yeast cell and 0:10:04.800 --> 0:10:07.160 then removed it from the yeast and they had to 0:10:07.200 --> 0:10:11.400 methylate it in order because they discovered that methylation protects 0:10:11.400 --> 0:10:15.480 the DNA from being digested by the host bacterium and 0:10:15.520 --> 0:10:19.360 then transplant it into a shell bacterium or a host 0:10:19.440 --> 0:10:25.319 bacterial cell. In these cases it was microplasma capriculum. So 0:10:26.040 --> 0:10:28.640 another problem they encountered along the way they talked about 0:10:28.720 --> 0:10:30.720 was that the cell wouldn't grow fast enough they were 0:10:30.760 --> 0:10:33.080 trying to do this, and so they ended up uh 0:10:33.200 --> 0:10:36.760 starting with the genome of a different organism. After microplasma 0:10:37.080 --> 0:10:40.959 genitalium didn't work well enough, they went with microplasma micodes 0:10:41.720 --> 0:10:45.880 and this organism had a much larger chromosome. It's bigger, 0:10:46.160 --> 0:10:49.200 harder to work with at over one million base pairs. 0:10:50.000 --> 0:10:52.160 Another thing that's really cool that they did is they 0:10:52.200 --> 0:10:55.640 put water marks in the d NA to leave no 0:10:55.920 --> 0:10:58.920 room for doubt as to whether the DNA was synthetic 0:10:59.040 --> 0:11:02.240 or natural. And what these were were stretches of non 0:11:02.360 --> 0:11:05.760 coding DNA, which DNA that doesn't actually make any proteins. 0:11:05.800 --> 0:11:08.479 You could just think of it as kind of metadata 0:11:08.679 --> 0:11:11.240 or the you know, slash slash notes sections in a 0:11:11.280 --> 0:11:14.440 piece of computer code. Uh. And these were used to 0:11:14.559 --> 0:11:19.920 code in written messages in the organism's DNA, including names 0:11:19.920 --> 0:11:23.480 of the authors on the research a web address associated 0:11:23.480 --> 0:11:26.360 with the project project so Ventor said, you know, if 0:11:26.400 --> 0:11:33.120 you can decode this, you can email us. Yeah. Three 0:11:33.240 --> 0:11:35.960 three quotes. They put some quotes in there. So one 0:11:36.000 --> 0:11:38.800 was a James Joyce quote, this is great to live, 0:11:39.160 --> 0:11:43.360 to air, to fall, to triumph, and to recreate life 0:11:43.360 --> 0:11:50.000 out of life. Good quote. A second one was from 0:11:50.040 --> 0:11:54.120 the book American Prometheus, which was about Robert Oppenheimer, and 0:11:54.280 --> 0:11:57.480 the quote was see things not as they are, but 0:11:57.600 --> 0:12:01.080 as they might be. That's a good one too, not 0:12:01.080 --> 0:12:02.800 not a bad open higher quote. I could think of 0:12:02.800 --> 0:12:05.880 one that would have been worse. Yeah, I have become death. 0:12:09.240 --> 0:12:13.320 The third was, of course from Richard Feynman, when Speineman 0:12:13.400 --> 0:12:16.560 said what I cannot build, I cannot understand. And that's 0:12:16.559 --> 0:12:19.040 the quote that I was referring to earlier. Right, I'm 0:12:19.120 --> 0:12:26.920 very sad that they didn't include the Frankenstein quote fire bad. 0:12:27.480 --> 0:12:30.800 But maybe maybe if we decode the that email address 0:12:30.960 --> 0:12:35.120 right when I can write when I make my synthetic bacterium, 0:12:35.720 --> 0:12:38.640 that's definitely going in there, you know. Listening to Ventor 0:12:38.760 --> 0:12:42.760 explain all of the different problems they encountered and fixes 0:12:42.880 --> 0:12:45.520 that they had to go through to to finally arrive 0:12:45.600 --> 0:12:49.640 at this research success, it is amazing that they were 0:12:49.679 --> 0:12:52.520 able to do this. I want to read one particular 0:12:53.040 --> 0:12:56.560 paragraph from Ventor's presentation from May two thousand ten about this, 0:12:57.080 --> 0:12:59.720 because I found this part really fascinating. It was about 0:12:59.760 --> 0:13:03.679 how the team had to develop debugging software to debug 0:13:03.880 --> 0:13:06.920 the organism because you know, they were they were creating 0:13:06.920 --> 0:13:11.800 a synthetic chromosome, so here's how it goes. So the 0:13:11.840 --> 0:13:14.800 team developed a new debugging software where we could test 0:13:14.840 --> 0:13:17.280 each synthetic fragment to see if it would grow in 0:13:17.320 --> 0:13:20.640 a background of wild type DNA, and we found that 0:13:20.720 --> 0:13:23.800 ten out of the eleven one hundred thousand base pair 0:13:23.880 --> 0:13:27.760 pieces we synthesized were completely accurate and compatible with a 0:13:27.840 --> 0:13:31.200 life forming sequence. We narrowed it down to one fragment, 0:13:31.480 --> 0:13:34.719 we sequenced it and found just one base pair had 0:13:34.760 --> 0:13:38.880 been deleted in an essential gene So accuracy is essential. 0:13:39.200 --> 0:13:41.880 There are parts of the genome where it cannot tolerate 0:13:41.960 --> 0:13:44.680 even a single error, and then there's parts of the 0:13:44.720 --> 0:13:47.079 genome where we can put in large blocks of DNA 0:13:47.080 --> 0:13:48.920 as we did with the water marks, and it can 0:13:48.920 --> 0:13:52.000 tolerate all kinds of errors. So it took about three 0:13:52.040 --> 0:13:54.559 months to find that error and repair it. And then 0:13:54.679 --> 0:13:57.280 one early morning at six am, we got a text 0:13:57.320 --> 0:14:01.000 from Dan saying, now the first blue colonies existed, and 0:14:01.040 --> 0:14:03.839 that's referring to you know that these things were reproducing 0:14:04.120 --> 0:14:07.200 within within a couple of days. I think they were. 0:14:07.240 --> 0:14:09.160 There were enough of them that you could physically see 0:14:09.160 --> 0:14:12.960 them in the Petrie dish. Wow, that's pretty impressive. I 0:14:13.000 --> 0:14:15.839 love this that they had to create a debugging program 0:14:15.880 --> 0:14:19.400 for the organism. Yeah, you imagine like that. That's a 0:14:19.480 --> 0:14:23.920 whole new discipline of quality assurance having to go through 0:14:24.040 --> 0:14:26.880 and because I you know, we know people who do 0:14:26.960 --> 0:14:29.200 q A for a living. They have to go through 0:14:29.280 --> 0:14:32.720 and test every single element of code. This is in 0:14:32.800 --> 0:14:37.240 fact biological code. It is exactly the the it's in line. 0:14:37.400 --> 0:14:38.960 I won't say it's exactly the same thing, but it's 0:14:39.000 --> 0:14:42.040 in line with that same sort of discipline. It's also 0:14:42.080 --> 0:14:46.760 absolutely what they had in Jurassic Park. Yes, using virtual 0:14:46.880 --> 0:14:51.840 reality and mr DNA. Uh So. Another thing that I 0:14:51.920 --> 0:14:53.880 just wanted to emphasize. I know I've already said it, 0:14:53.920 --> 0:14:56.400 but I just find so fascinating about this and what 0:14:56.440 --> 0:15:00.480 it illuminates about the nature of life is how zilient 0:15:00.640 --> 0:15:03.160 the DNA code is in some ways and how fragile 0:15:03.240 --> 0:15:07.280 it is in other ways. A missing a missing or 0:15:07.360 --> 0:15:11.280 deleted base pair in one section of the code can 0:15:11.360 --> 0:15:16.040 completely make you a non viable organism, but other parts 0:15:16.080 --> 0:15:18.640 you can just do all kinds of crazy stuff with. Well, again, 0:15:18.680 --> 0:15:20.760 I think if you if you compare that to the 0:15:20.840 --> 0:15:24.640 idea of software like there are there are errors you 0:15:24.680 --> 0:15:26.920 can make when you're coding something in software, and it 0:15:27.040 --> 0:15:29.880 might make something unusual happen when you're trying to execute 0:15:29.880 --> 0:15:32.240 the software. But there are other errors you can make 0:15:32.280 --> 0:15:35.920 that can make that software completely unstable, and it will 0:15:36.000 --> 0:15:38.400 won't even run problem, not only crash, but crash your 0:15:38.520 --> 0:15:41.160 entire system. Right, I'm thinking about every video game that's 0:15:41.200 --> 0:15:43.640 been released over the last twelve months. But maybe that's 0:15:43.960 --> 0:15:48.440 just because of a little bitter about bug game destroying 0:15:48.480 --> 0:15:52.560 bugs released on day one. I don't really know which 0:15:52.560 --> 0:15:56.320 one is you're referring to the pretty much yeah anyway, 0:15:56.560 --> 0:15:59.000 well but but but but I'm saying that the similarity 0:15:59.040 --> 0:16:01.280 really is there, and as much as I'm making fun 0:16:01.520 --> 0:16:04.840 of of of something that's running rampant through the video 0:16:04.840 --> 0:16:08.520 game industry, the idea being that, uh, when you start 0:16:08.560 --> 0:16:11.760 to think about d n A is being similar to software, 0:16:12.680 --> 0:16:16.520 at least in a in a general sense, then you're like, oh, yeah, 0:16:16.560 --> 0:16:20.160 I get it. Because some errors in encoding are not 0:16:20.360 --> 0:16:22.200 that huge a deal. You might be able to pick 0:16:22.280 --> 0:16:24.960 up on it, uh if something unusual happens while you're 0:16:24.960 --> 0:16:29.680 executing the code, and others are absolutely deal breakers. Yeah, 0:16:29.680 --> 0:16:32.520 but anyway, I I think this is so cool that 0:16:32.600 --> 0:16:36.800 you can chart how they went from information to chemistry 0:16:36.840 --> 0:16:41.280 to biology, like there was the entire pathway from just 0:16:42.040 --> 0:16:45.880 from idea to life. And so this first synthetic cel 0:16:46.120 --> 0:16:49.880 was called micro plasma MI codes j C v I 0:16:49.920 --> 0:16:53.960 for j Craig vinor institute sin one point, oh, not 0:16:54.200 --> 0:17:00.080 sin like like doing evil and synthetic. Yeah, so in 0:17:00.240 --> 0:17:02.400 one point. Oh what does it mean? Well, it helps 0:17:02.440 --> 0:17:04.959 us understand better the chemical basis of life. That's one 0:17:05.040 --> 0:17:07.160 big thing where we you know, learn a lot about 0:17:07.640 --> 0:17:11.040 about chromosomes and DNA and the role different genes play 0:17:11.560 --> 0:17:14.479 than we can do continuing research. Now that we have 0:17:14.560 --> 0:17:17.919 the basis for creating synthetic organisms. Uh, it might be 0:17:18.000 --> 0:17:21.920 useful in synthesizing germs that cause diseases so those diseases 0:17:21.960 --> 0:17:25.320 can be treated and overcome. Uh, it might be useful 0:17:25.359 --> 0:17:29.680 for creating synthetic biological organisms like we were talking about earlier. 0:17:29.760 --> 0:17:32.760 So you know, if you want to make some algae 0:17:32.800 --> 0:17:36.080 that could remediate waste products or capture CEO two, or 0:17:36.119 --> 0:17:40.680 create biofuels or food or or whatever. Yes, so these 0:17:40.720 --> 0:17:43.880 are uh, you know, basic ideas well where you visit 0:17:43.960 --> 0:17:45.600 that towards the end of the episode two, when we 0:17:45.640 --> 0:17:49.440 start talking about the the various things you can do 0:17:49.520 --> 0:17:53.800 with the discipline of synthetic biology. This is a pretty 0:17:53.840 --> 0:17:57.760 important part of that. Yeah, an amazing first step. Yeah. 0:17:57.880 --> 0:18:02.760 So the interesting thing is that's not where the story ends. 0:18:02.840 --> 0:18:06.960 That was, but we have continued the advancement of synthetic 0:18:07.000 --> 0:18:10.639 biology since then. Yeah, an inventor and his team specifically have. 0:18:10.880 --> 0:18:13.440 After they created SIN one point. Oh, they set out 0:18:13.480 --> 0:18:16.919 with a new goal to design a bacterium with the 0:18:17.160 --> 0:18:21.359 absolute minimum GENO. And why would you want to do that? Well, 0:18:21.640 --> 0:18:24.120 they wanted to figure out what bits of code are 0:18:24.280 --> 0:18:27.760 essential and what are not essential. Yeah, and this is 0:18:27.960 --> 0:18:30.520 this is really smart to do, I think, because we 0:18:30.560 --> 0:18:33.199 had this problem last time, right where some parts of 0:18:33.200 --> 0:18:35.280 code it seems like it don't matter. You can change 0:18:35.320 --> 0:18:38.560 them with no no big impact. Other parts can our 0:18:38.640 --> 0:18:41.680 our game breakers. Well, and we've also found that there 0:18:41.720 --> 0:18:47.160 are segments of DNA within different organisms that ultimately originated 0:18:47.240 --> 0:18:52.199 from other species and don't have any useful uh you know, 0:18:52.400 --> 0:18:57.240 useful performance, or they don't do anything, or it's a 0:18:57.359 --> 0:19:00.960 duplicate of something else that already works perfectly. Right, So 0:19:01.119 --> 0:19:06.280 maybe we can make life better more efficient, cut out 0:19:06.320 --> 0:19:09.879 the fat and and Furthermore, Yeah, just just what you 0:19:09.920 --> 0:19:12.879 were talking about, Joe, just figure out exactly what the 0:19:12.920 --> 0:19:16.359 different pieces do, because because even though we've we've sequenced 0:19:16.400 --> 0:19:21.240 plenty of genomes, we really don't understand very well what 0:19:21.400 --> 0:19:24.479 all of the individual genes do and and specifically how 0:19:24.520 --> 0:19:27.679 they work together in the genome. That's that's way beyond 0:19:27.760 --> 0:19:31.000 us right now. Um but this can help us learn hypothetically. 0:19:31.080 --> 0:19:34.840 I mean, their first attempts totally failed, so uh and 0:19:34.840 --> 0:19:36.800 and and no one was more surprised than Ventor. He 0:19:37.080 --> 0:19:40.640 there's a great quote where he was like, I was shocked, Like, well, 0:19:40.680 --> 0:19:43.080 you know, I love you, I love the idea. We 0:19:43.200 --> 0:19:45.760 gotta remember you learn more through failure than you do 0:19:45.840 --> 0:19:50.040 through success. Completely that that is literally how science works. 0:19:50.320 --> 0:19:53.320 Um So, ideally you can learn from other people's failures 0:19:53.320 --> 0:19:56.000 in your own successes. That way you look like you 0:19:56.040 --> 0:20:00.119 are awesome, right, much preferable. But yeah, okay, So the 0:20:00.119 --> 0:20:03.880 first attempt that they made, two different teams each independently 0:20:04.000 --> 0:20:07.800 tried to build a bacterium from the ground up, and 0:20:08.200 --> 0:20:10.320 it was just it was too ambitious given our current 0:20:10.800 --> 0:20:14.960 aforementioned lack of knowledge about genetics and genomics. Um So, 0:20:15.040 --> 0:20:18.240 to give you like a metaphor here additive manufacturing a 0:20:18.320 --> 0:20:22.480 genome didn't work. But but what about whittling something down? 0:20:22.520 --> 0:20:24.879 What about removing all the parts of the genome that 0:20:24.920 --> 0:20:27.920 are not the statue of David gotcha? All right? So 0:20:27.920 --> 0:20:32.080 so the traditional subtractive approach where you you are taking 0:20:32.080 --> 0:20:36.280 away everything that is not necessary for whatever the finished 0:20:36.280 --> 0:20:39.440 product needs to be. So so they took SIN one 0:20:39.440 --> 0:20:42.600 point oh and they started labeling all of its pieces. 0:20:42.640 --> 0:20:47.720 They took its nine one genes and played with deleting 0:20:47.920 --> 0:20:52.280 or disrupting different sections in turn. And when they plugged 0:20:52.320 --> 0:20:56.439 the resulting experiments into a m capric column, it did, 0:20:56.800 --> 0:20:59.879 you know, either be viable or totally not viable? And 0:21:00.240 --> 0:21:02.119 if if it died, if it was not viable, they 0:21:02.200 --> 0:21:06.119 knew that they had removed something important science. This this 0:21:06.160 --> 0:21:10.760 makes me think of what early medicine must have been, like, yeah, 0:21:10.800 --> 0:21:13.359 it turns out you needed that one. It reminds me 0:21:13.440 --> 0:21:15.040 of that moment where Bones is, you know, in the 0:21:15.040 --> 0:21:21.840 twentieth century, and he's like these savages. But but eventually 0:21:22.200 --> 0:21:25.240 it produced what they call SIN two point oh, which 0:21:25.400 --> 0:21:28.719 was the first micro but with a genome smaller than 0:21:28.760 --> 0:21:33.480 the world's smallest known natural genome, which is microplasma genitalium, 0:21:33.760 --> 0:21:39.160 which has only five UM. And then along came SIN 0:21:39.359 --> 0:21:43.440 three point oh, which is a living, reproducing organism with 0:21:43.640 --> 0:21:47.400 just four hundred and seventy three genes. They trimmed out 0:21:47.440 --> 0:21:49.440 all of those non essential or a lot of those 0:21:49.520 --> 0:21:53.400 not essential and duplicate genes. Um. But but even at 0:21:53.400 --> 0:21:56.840 this point the critter still might contain some some coding. 0:21:56.880 --> 0:21:59.920 Blow to the researchers are not sure what a hundred 0:22:00.200 --> 0:22:02.919 and forty nine of those genes do. I do like 0:22:02.960 --> 0:22:04.680 the idea that they can cut out a whole bunch 0:22:04.680 --> 0:22:08.080 of genes and pass the savings onto you. I think 0:22:08.119 --> 0:22:12.280 that's that's very forward thinking. Other than other than those 0:22:12.320 --> 0:22:16.800 amazing savings, Um, why would you want to do this? Uh? Well, 0:22:16.920 --> 0:22:20.439 this resulting organism SIN three point oh can be used 0:22:20.520 --> 0:22:24.320 to study what specific genes do, both the ones that 0:22:24.320 --> 0:22:27.040 it currently possesses and also all of the bits that 0:22:27.119 --> 0:22:29.639 they removed from versions one and two in order to 0:22:29.720 --> 0:22:32.399 make three. By by adding them back in one at 0:22:32.400 --> 0:22:36.439 a time, they can watch the results play out. And furthermore, uh, 0:22:36.600 --> 0:22:40.240 the SIN three point oh grows like and reproduces really fast. 0:22:40.600 --> 0:22:43.879 So uh SIN three point o cell populations double in 0:22:43.920 --> 0:22:48.440 about three hours. So that's a great laboratory tool. And 0:22:48.440 --> 0:22:51.439 and eventually they're hoping to create a living organism for 0:22:51.600 --> 0:22:56.560 which the entire genome is understood. And I cannot stress 0:22:57.240 --> 0:23:00.000 how rad that would be. I mean, I mean, even 0:23:00.320 --> 0:23:05.200 if you're only talking about the world's very biddiest genomic code, uh, 0:23:05.520 --> 0:23:07.920 because you know, like I said, like just because we can, 0:23:07.960 --> 0:23:10.760 we can sequence the whole genome, even very much more 0:23:10.800 --> 0:23:17.240 complex genomes. Humans for example, have some thousand genes. Uh 0:23:17.359 --> 0:23:19.639 that that absolutely doesn't mean that we know what what 0:23:19.680 --> 0:23:23.119 all of that coding does. It would be a really huge, 0:23:23.200 --> 0:23:26.400 really huge mile marker. And I think what's really cool 0:23:26.520 --> 0:23:29.600 here also is by adding in those genes one at 0:23:29.600 --> 0:23:32.040 a time and seeing what they do. It's not even 0:23:32.080 --> 0:23:35.200 as simple as that, because genes can interact with one another. 0:23:35.320 --> 0:23:37.639 So sometimes it may be that you let's say that 0:23:37.680 --> 0:23:43.080 you've got one version of this artificial life form and 0:23:43.119 --> 0:23:45.040