WEBVTT - Editing Genes with CRISPR 0:00:00.200 --> 0:00:07.120 Brought to you by Toyota. Let's go places. Welcome to 0:00:07.280 --> 0:00:14.440 Forward Thinking as Welcome to Forward Thinking, the podcast that 0:00:14.480 --> 0:00:16.800 looks at the future and says, d n A, You're 0:00:16.840 --> 0:00:19.160 in my heart d n A, in fact, you're in 0:00:19.239 --> 0:00:22.920 every part of my body. I'm Jonathan Strickland and I'm 0:00:23.000 --> 0:00:26.520 Joe McCormick. And how true that is because d n 0:00:26.520 --> 0:00:30.520 A is truly the blueprint for life. Yeah, you know 0:00:30.560 --> 0:00:33.440 what it feels to me, Like I've heard you say 0:00:33.520 --> 0:00:36.279 that before. You might not have, because I don't think 0:00:36.320 --> 0:00:38.479 I said that last time. I just want to let 0:00:38.479 --> 0:00:41.800 the listeners in on a little secret. So the first 0:00:41.840 --> 0:00:45.440 time we recorded this episode, there was an audio glitch 0:00:45.520 --> 0:00:48.720 where we lost the first half of it. Yep. Um, 0:00:48.800 --> 0:00:51.280 So what we're going to be doing now is re 0:00:51.280 --> 0:00:54.240 recording part of this episode. I say that in case 0:00:54.280 --> 0:00:57.200 you're wondering why we might have like a callback joke 0:00:57.280 --> 0:01:00.640 at the end that calls back to nothing. It's like 0:01:00.680 --> 0:01:03.120 we're stuck in a time loop, like we went through 0:01:03.160 --> 0:01:06.640 that nebula with con and then what happens. We're definitely 0:01:06.959 --> 0:01:10.440 not trying to have like some sort of inside joke 0:01:10.520 --> 0:01:12.360 that you're not privy to. You would have been privy 0:01:12.400 --> 0:01:15.440 to it had the technical glitch not happened. That being said, 0:01:15.840 --> 0:01:18.520 what are we talking about today, Joe, Well, we're talking 0:01:18.520 --> 0:01:24.240 about Mr DNA. Someone someone's been watching the Jurassic World 0:01:24.680 --> 0:01:28.560 trailer and just what did you come from? You know, 0:01:28.600 --> 0:01:31.279 I always love that moment in Jurassic Parker, Mr DNA 0:01:31.440 --> 0:01:33.240 comes out and they explain to you about the wondrous 0:01:33.240 --> 0:01:35.880 of DNA. But everybody's heard about DNA by now. It's 0:01:36.000 --> 0:01:39.600 it's no longer a big surprise that we've that we've 0:01:39.640 --> 0:01:42.679 got these coding segments and the cells in our body 0:01:42.760 --> 0:01:45.840 that tell us what kind of body plans to produce. 0:01:45.920 --> 0:01:49.120 They make the proteins that make our bodies, and so 0:01:49.240 --> 0:01:52.720 we get our traits are sort of inherited physical traits 0:01:52.840 --> 0:01:56.440 from our d N A. And this is long led 0:01:56.480 --> 0:02:00.280 people to wonder like, Wow, could I make myself better 0:02:00.440 --> 0:02:03.480 if I could just change my DNA? Could I head 0:02:03.480 --> 0:02:07.760 off any disorders or diseases? More importantly, I mean, and 0:02:08.080 --> 0:02:10.079 this is the thing that we definitely said the first time, 0:02:10.400 --> 0:02:12.919 if we were going to change something about you, Jonathan, 0:02:13.520 --> 0:02:16.280 it would absolutely be the color of your beard. That's right. 0:02:16.400 --> 0:02:19.040 That is something we did. Purple beard it would need 0:02:19.080 --> 0:02:21.160 to be purple. I'm so I'm so pleased that you 0:02:21.200 --> 0:02:25.480 remember that. I was listening back to the garbled audio 0:02:25.560 --> 0:02:27.040 that we had and we got to the point about 0:02:27.080 --> 0:02:29.440 my purple beard, and I thought, I don't worry about 0:02:29.480 --> 0:02:31.520 that being talked about again because it's not in our notes. 0:02:31.560 --> 0:02:35.640 But sucka darn it. Yeah. I mean, the technology that 0:02:35.680 --> 0:02:37.840 we have to change something like the color of someone's 0:02:37.880 --> 0:02:41.480 beard right now is like bleach and die. Yeah. It's 0:02:41.520 --> 0:02:44.720 not something about, you know, changing the innate properties of 0:02:44.720 --> 0:02:48.400 me so that I'm growing purple beard here right. But 0:02:48.520 --> 0:02:51.840 if we want to change other traits, like, for example, 0:02:52.360 --> 0:02:57.400 diseases like like cancer, something that is heritable, you can't 0:02:57.520 --> 0:03:00.359 just drink bleach and die, or I mean you could, 0:03:00.400 --> 0:03:02.600 but I don't recommend that. That's not a medical treatment. 0:03:02.600 --> 0:03:04.639 Please don't do that. Don't do that. No, No, We're 0:03:04.639 --> 0:03:09.120 talking about a more serious scenario where imagine that, um, 0:03:09.240 --> 0:03:12.880 we've reached the level of genetic sophistication where you can 0:03:13.120 --> 0:03:16.720 produce an embryo that's going to be your child, and 0:03:16.840 --> 0:03:18.840 you can look at the d n A of that 0:03:18.960 --> 0:03:23.280 embryo and analyze it, run it through the computer and say, oh, No, 0:03:23.960 --> 0:03:27.000 it looks like this child is going to have a 0:03:27.080 --> 0:03:30.919 genetic condition which makes him or her prone to any 0:03:31.000 --> 0:03:33.880 number of you know, diseases, something that that we wouldn't 0:03:33.880 --> 0:03:36.160 want for this child that the embryo is going to 0:03:36.240 --> 0:03:39.120 grow to be. So could we make a little edit 0:03:40.240 --> 0:03:43.400 and fix the d n A so that the child 0:03:43.520 --> 0:03:46.480 doesn't have to suffer from this disease? If you could 0:03:46.520 --> 0:03:48.960 do such a thing, Obviously, lots of people would want 0:03:49.000 --> 0:03:52.680 that opportunity, right, And we've talked about this very subject 0:03:52.720 --> 0:03:55.360 a couple of times in previous episodes, including one about 0:03:55.480 --> 0:03:58.360 gene therapy. But the reason why we're bringing it up 0:03:58.360 --> 0:04:02.120 again now is that we wanted to really focus on 0:04:02.320 --> 0:04:07.320 a system that makes the potentially could make editing genes 0:04:07.600 --> 0:04:12.840 far simpler and more efficient, less expensive than previous methods, 0:04:12.880 --> 0:04:17.200 and therefore has the potential to revolutionize the way we 0:04:17.200 --> 0:04:20.760 work with genes. And because of this revolutionary quality, this 0:04:20.800 --> 0:04:26.039 new system is being heralded with caution, right, we should say, 0:04:26.080 --> 0:04:30.360 lots of scientists have recently spoken up saying, hey, we 0:04:30.400 --> 0:04:33.000 need to we need to take stock of where we 0:04:33.080 --> 0:04:37.480 are in gene editing technology right now and and make 0:04:37.520 --> 0:04:40.560 sure that we're taking all the proper precautions and sort 0:04:40.560 --> 0:04:43.560 of treading carefully on this ground because we get into 0:04:43.560 --> 0:04:46.719 some pretty weird territory when you talk about editing genes. 0:04:46.760 --> 0:04:49.920 But let's let's talk about the new system itself. Well, 0:04:49.920 --> 0:04:53.279 here's the crazy thing. The system, if you think of 0:04:53.320 --> 0:04:58.120 it as the actual process, is not new. The new 0:04:58.160 --> 0:05:01.000 part is that we're employing it or can employ or 0:05:01.040 --> 0:05:03.160 that we know that it exists at all. Yeah. The 0:05:04.400 --> 0:05:07.360 cool thing about this, the super cool thing about this, 0:05:07.560 --> 0:05:11.120 is that it's a natural process that was observed many 0:05:11.160 --> 0:05:14.839 years ago but not understood until relatively recently. Yeah. And 0:05:14.920 --> 0:05:20.040 so this process is known as the Crisper cast nine system. 0:05:20.120 --> 0:05:22.719 And the Crisper cast nine system is based on a 0:05:22.920 --> 0:05:28.480 naturally occurring system found in bacteria. In it's an immune 0:05:28.720 --> 0:05:33.320 process in bacterial cells, right, And crisper is not referring 0:05:33.320 --> 0:05:37.160 to some kind of refrigeration system within bacteria. It's an acronym. Right, 0:05:37.200 --> 0:05:42.960 It's an acronym for clustered, regularly interspaced short palindromic repeats, 0:05:43.000 --> 0:05:47.200 and that refers to sections of DNA code in these 0:05:47.400 --> 0:05:52.039 bacteria and how they use this system to protect themselves 0:05:52.120 --> 0:05:56.320 from viruses. So, the blocks of repeated gene sequences were 0:05:56.440 --> 0:06:00.560 first observed in bacterial cells and mentioned to paper by 0:06:00.640 --> 0:06:04.799 Japanese researchers in the Journal of Bacteriology in nineteen seven, 0:06:05.120 --> 0:06:07.920 and at the time scientists didn't know what they did. 0:06:07.960 --> 0:06:10.200 They're like, no, we saw these things, we don't know 0:06:10.279 --> 0:06:13.320 what the purpose is, right, It wouldn't be until several 0:06:13.400 --> 0:06:17.679 years later that more observations would give us insight into 0:06:17.760 --> 0:06:21.400 what was actually happening. A couple of decades. Really, yeah, 0:06:21.400 --> 0:06:24.279 so we now know that these are used to create 0:06:24.320 --> 0:06:28.000 a system within the bacteria that protects the bacteria from viruses. 0:06:28.400 --> 0:06:32.560 And it's actually what's known as an adaptive immune system. 0:06:32.680 --> 0:06:35.920 Now what is that so? Adaptive means that you are 0:06:36.640 --> 0:06:41.000 building up like you're you're you're constantly evolving and tweaking 0:06:41.080 --> 0:06:43.200 your your immune system so that you can fight off 0:06:43.320 --> 0:06:47.760 a broader array of potential pathogens. All right. That's why 0:06:47.920 --> 0:06:50.960 vaccines work, because they give your body just a little 0:06:50.960 --> 0:06:54.919 bit of a inactive virus to look at, to observe, 0:06:55.480 --> 0:06:57.919 to take a little bit of the protein from the 0:06:58.000 --> 0:07:01.880 virus shell from and to incorporate that inter into your 0:07:01.960 --> 0:07:05.200 immune system so that in the future, your immune system 0:07:05.240 --> 0:07:08.240 can recognize that type of virus and say like no, 0:07:08.480 --> 0:07:13.000 thank you, sir, exactly. Yeah, And and so this is 0:07:13.040 --> 0:07:16.080 sort of bacteria's approach. Actually it's not sort of. It 0:07:16.160 --> 0:07:22.440 is bacterious approach to fighting off viruses. If a bacteria survives, uh, 0:07:22.480 --> 0:07:25.640 and encounter with a new type of virus, it adds 0:07:25.720 --> 0:07:30.920 that information to its quote unquote like database of viral info. Yeah. Yeah, 0:07:30.960 --> 0:07:35.320 and that's that's what these little crisper strands are there. 0:07:35.360 --> 0:07:38.720 There these strands of of little bits of repeating DNA 0:07:38.880 --> 0:07:42.880 that have little bits of viral codes smushed in representing 0:07:43.040 --> 0:07:46.760 all of the viruses that that bacteria or that bacteria's 0:07:46.840 --> 0:07:50.080 ancestors has run across. Right, because it's inheritable. So this 0:07:50.720 --> 0:07:53.880 is really interesting for lots of different reasons. Okay, so 0:07:53.960 --> 0:07:58.400 to get into how we could use this bacterial immune 0:07:58.440 --> 0:08:01.560 system or a version of it to edit jeans, let's 0:08:01.560 --> 0:08:04.480 look at how it actually works in the field in 0:08:04.560 --> 0:08:08.560 real life. Right, what happens when a bacterium that has 0:08:08.640 --> 0:08:12.200 this defense mechanism encounters of virus. Okay, here's how it 0:08:12.280 --> 0:08:16.200 goes down. You got your virus. Now your virus. Imagine 0:08:16.200 --> 0:08:18.120 that you've got a little it looks like a little spacecraft, 0:08:18.720 --> 0:08:23.360 especially if you played Yards Revenge, watched an Atari documentary recently. Anyway, 0:08:23.560 --> 0:08:26.800 so you've got this little virus inside this shell is 0:08:27.040 --> 0:08:31.040 viral DNA, and the way of virus replicates is it 0:08:31.160 --> 0:08:35.720 ends up infecting a host cell. So some viruses target 0:08:35.880 --> 0:08:38.679 very specific cells and ignore anything else. It's all through 0:08:38.720 --> 0:08:42.200 protein markers. Anyway, the virus lands on a host cell 0:08:42.280 --> 0:08:46.360 and it injects its own DNA into the host cell. 0:08:47.120 --> 0:08:51.880 That DNA essentially hijacks all the assets inside the host 0:08:51.920 --> 0:08:58.000 cell to start replicating more viral DNA and virus shells. 0:08:58.040 --> 0:09:01.640 So it's essentially telling the host, uh, sell, hey, I 0:09:01.679 --> 0:09:04.200 know what you're doing is tot's important, but you gotta 0:09:04.280 --> 0:09:07.320 drop it and make some of this stuff asap. And 0:09:07.360 --> 0:09:09.440 that's what the host cell does. It's it's getting new 0:09:09.480 --> 0:09:12.800 instructions and it just starts churning out more and more 0:09:13.600 --> 0:09:18.199 viruses until you know, more instances of the same virus 0:09:18.200 --> 0:09:20.360 I guess I should say, until you get to a 0:09:20.400 --> 0:09:23.960 point where the little virus shells all break free from 0:09:23.960 --> 0:09:26.760 the host cell, killing it in the process, and then 0:09:26.800 --> 0:09:28.600 they go on their merry way to do the same 0:09:28.600 --> 0:09:31.040 thing to other host cells. And that's how the virus 0:09:31.120 --> 0:09:36.400 spreads So that's how a virus typically would attack a bacterium. 0:09:36.400 --> 0:09:39.480 But let's say that the bacterium actually has this adaptive 0:09:39.920 --> 0:09:43.440 immune system we just mentioned what's going on there. Well, 0:09:43.480 --> 0:09:46.640 assuming that the bacterium or one of its ancestors had 0:09:46.720 --> 0:09:49.800 encountered that particular type of virus before, it's gonna have 0:09:50.320 --> 0:09:53.440 a strand in its DNA that matches part of the 0:09:53.559 --> 0:09:58.400 viral DNA. And when it detects the the intrusion of 0:09:58.520 --> 0:10:04.120 viral DNA that the bacteriums DNA will end up creating 0:10:04.120 --> 0:10:08.080 a strand of RNA, actually two strands one strand of 0:10:08.080 --> 0:10:15.040 that RNA. We'll have pairs well half of a pair, uh, 0:10:15.080 --> 0:10:17.520 that you would find in the double helix that match 0:10:17.640 --> 0:10:19.800 up to the viral DNA. Yeah. Sort of think about 0:10:19.840 --> 0:10:22.439 the way that a key is made to fit the 0:10:22.480 --> 0:10:25.680 pins in a certain lock. The key has these particular 0:10:25.800 --> 0:10:28.720 series of bumps and grooves that will fit into that lock. 0:10:29.320 --> 0:10:32.600 This immune system device has RNA that's like a key 0:10:32.640 --> 0:10:35.400 that fits the virus. Yeah. So if you think of 0:10:35.679 --> 0:10:39.160 h d NA, like, you know, you've got this double helix. 0:10:39.280 --> 0:10:41.000 If you imagine you straighten it out so it looks 0:10:41.000 --> 0:10:44.160 like it's a ladder, and each run of the ladder 0:10:44.200 --> 0:10:49.360 is actually a pair that joined together. The RNA is 0:10:49.480 --> 0:10:51.880 one half of that ladder that can match up to 0:10:52.160 --> 0:10:56.320 half of the virus DNA. Now it creates an enzyme 0:10:56.960 --> 0:11:00.240 um it's actually it's a protein that the casting line 0:11:00.280 --> 0:11:02.560 protein and creates a few things, but the castline protein 0:11:02.640 --> 0:11:04.360 is the one that's important for this discussion, known as 0:11:04.360 --> 0:11:10.240 an indo nuclea, and it ends up unwinding separating the 0:11:10.840 --> 0:11:14.640 viral DNA so that the RNA created by the bacterium 0:11:14.679 --> 0:11:17.920 will join up to the viral DNA, and it also 0:11:18.520 --> 0:11:22.240 will snip the viral DNA at a very specific point 0:11:22.679 --> 0:11:26.760 and this essentially deactivates the viral DNA, killing it so 0:11:26.840 --> 0:11:30.360 that the viral attack fails. It is not able to 0:11:30.440 --> 0:11:35.120 hijack the cells operations and create more viruses, uh, which 0:11:35.200 --> 0:11:37.720 is you know, pretty awesome. And also, like we were 0:11:37.720 --> 0:11:40.520 mentioning before, if it happens to be the case where 0:11:40.520 --> 0:11:44.040 the bacterium or its ancestors has never encountered that particular 0:11:44.120 --> 0:11:47.320 virus but it survives the attack, then for that information 0:11:47.360 --> 0:11:51.280 gets added to the bacteriums DNA so that future encounters 0:11:51.280 --> 0:11:54.840 with that virus will be handled with extreme prejudice for 0:11:54.920 --> 0:11:58.920 that bacterium and all its descendants, right, and in a 0:11:58.960 --> 0:12:04.000 word about these these these casts proteins and specifically CAST nine, 0:12:04.040 --> 0:12:07.080 which is the important one DAYA that stands for Crisper 0:12:07.120 --> 0:12:12.079 associated proteins and number nine a number nine like a 0:12:12.440 --> 0:12:15.480 like love potion number nine, yes, and are probably not. 0:12:15.720 --> 0:12:19.880 This is like death potion number nine. And the Crisper 0:12:19.960 --> 0:12:22.560 arrays make a bunch of these different cast proteins that 0:12:22.600 --> 0:12:25.880 all have different jobs, like like integrating those new bits 0:12:25.880 --> 0:12:31.320 of those like wanted wanted poster sequences into the Crisper strand. 0:12:31.720 --> 0:12:34.400 And CAST nine's job, which it is really good at, 0:12:34.920 --> 0:12:40.760 is uh, both to unzip the DNA and to snip 0:12:40.800 --> 0:12:45.600 the ends at that specific location along the helixes hees. 0:12:46.080 --> 0:12:49.280 So this indo nuclease, this CAST nine is it's kind 0:12:49.320 --> 0:12:51.520 of like a little pair of scissors. A lot of 0:12:51.520 --> 0:12:54.800 people have computed molecular scissors, and people say can go 0:12:54.880 --> 0:12:59.840 in and make little snips and cuts to DNA, which, obviously, 0:13:00.000 --> 0:13:02.400 once you see something like that in action in UH 0:13:02.520 --> 0:13:05.800 in the microbial world, you start to think, huh, I 0:13:05.880 --> 0:13:08.080 wonder if we could take advantage of that. Yeah, because 0:13:08.080 --> 0:13:11.640 it's able to cut it at a precise location and 0:13:11.800 --> 0:13:16.080 cut at the same location across both of the helices, 0:13:16.080 --> 0:13:18.160 as we were saying, so that you have an extreme 0:13:18.240 --> 0:13:20.640 level of control, which is really important if you want 0:13:20.679 --> 0:13:25.000 to do something like target a very specific strand of 0:13:25.080 --> 0:13:27.199 DNA or section of a strand of DNA, I should 0:13:27.200 --> 0:13:31.440 say right. And this is especially interesting because research has 0:13:31.480 --> 0:13:35.600 shown that this crisper cast nine SmackDown of genes may 0:13:35.640 --> 0:13:38.880 also occur within a bacterial cell itself. It's not just 0:13:39.040 --> 0:13:43.000 in application to viruses. In research that was published in 0:13:43.080 --> 0:13:46.800 Nature in from a team out of Emery University, a 0:13:46.880 --> 0:13:50.640 particular bacteria was shown to to use crisper Cast nine 0:13:50.679 --> 0:13:54.280 to shut down one of its own lipoproteins. And okay. 0:13:54.280 --> 0:13:59.080 In bacteria, lipoproteins help the bacteria attached to a host cell, 0:13:59.440 --> 0:14:04.000 but they also trigger inflammatory responses in a host, which 0:14:04.120 --> 0:14:07.480 triggers the host summune system, which sucks for the bacteria. 0:14:07.880 --> 0:14:11.760 Um By shutting off this lipoprotein, it lets the bacteria 0:14:11.880 --> 0:14:15.480 kind of fly under the radar, multiplying without interference and 0:14:15.640 --> 0:14:21.320 biding its time until it goes pathogenic. Interesting. Yeah, another 0:14:21.680 --> 0:14:25.360 cool thing. This is almost a tangent, but a cool 0:14:25.440 --> 0:14:29.400 side effect of This is that you can look at 0:14:29.960 --> 0:14:33.480 UH back you know, the the DNA of a bacteria 0:14:33.680 --> 0:14:37.160 and or or of bacteria I guess I should say UH, 0:14:37.200 --> 0:14:40.400 and be able to tell a lot about it, including 0:14:40.520 --> 0:14:43.520 you know, which viruses it has encountered in the past. 0:14:44.400 --> 0:14:47.760 And this kind of ends up being a fingerprinting approach. 0:14:47.920 --> 0:14:51.720 So let's say that there is a bacterial outbreak somewhere 0:14:51.880 --> 0:14:54.119 some some sort of illness that is due to bacteria. 0:14:54.320 --> 0:14:58.200 For example, let's call you know, food poisoning. We hear 0:14:58.280 --> 0:15:02.760 at how stuff works, are familiar or with that particular idea. Um, 0:15:02.840 --> 0:15:05.360 So let's say that you have an outbreak of food poisoning. 0:15:05.520 --> 0:15:09.920 You could end up analyzing the bacteria and by looking 0:15:09.960 --> 0:15:13.600 at the this information which viruses encountered in the past, 0:15:14.480 --> 0:15:17.680 you could possibly use that information to trace it back 0:15:17.720 --> 0:15:21.560 to wherever the source of the food poisoning was. So 0:15:21.600 --> 0:15:27.640 it's actually got some interesting forensic identification processes. It's being 0:15:27.800 --> 0:15:31.800 used like that by the cultured dairy industry to check 0:15:31.840 --> 0:15:35.920 whether the strains of helpful bacteria that they use in 0:15:36.040 --> 0:15:39.560 order to make cheese, at yogurt and delicious stuff like 0:15:39.600 --> 0:15:42.760 that that requires bacteria for the process to check whether 0:15:43.000 --> 0:15:47.160 their bacteria are immune against common viruses. They can then 0:15:47.160 --> 0:15:52.520 select bacteria colonies of bacteria that are stronger and more 0:15:52.600 --> 0:15:56.320 likely to remain effective at driving these processes. So it's 0:15:56.360 --> 0:16:00.240 it's like a more technical bacterial version of breeding really 0:16:00.280 --> 0:16:03.440 healthy animals to make sure that their offspring are healthy. 0:16:04.600 --> 0:16:09.520 I'm just imagining, like the Saruman of cheese over his factory, 0:16:09.800 --> 0:16:15.160 breeding the uricai of bacteria to make delicious cheese. I 0:16:15.200 --> 0:16:19.880 don't get the reference. Tom kidding, kidding, says the guy 0:16:19.880 --> 0:16:24.480 with the Lord of the rings. Tonight we dine on cheese, 0:16:25.320 --> 0:16:28.480 all right. So where does the gene editing come in? Well, 0:16:28.800 --> 0:16:33.280 in a group led by Jennifer DOWDNA and Emmanuel Charpentier 0:16:33.840 --> 0:16:37.000 and apologies if I mispronounced that, I did my best, 0:16:37.720 --> 0:16:41.600 but they published findings in Science that the Crisper system 0:16:42.000 --> 0:16:44.880 could be used to edit any kind of DNA you 0:16:44.960 --> 0:16:49.720 want through quote RNA programmable genome editing. And that was 0:16:49.720 --> 0:16:53.080 in a paper called a programmable dual RNA guided DNA 0:16:53.240 --> 0:17:00.080 into nuclease Inadaptive Bacterial immunity. Yeah. So subsequent studies have 0:17:00.320 --> 0:17:03.000 shown that it works not only in bacteria with Crisper 0:17:03.000 --> 0:17:07.000 based immune systems, but in all kinds of organisms and 0:17:07.080 --> 0:17:11.840 potentially in humans. So with crisper based gene editing, it's 0:17:11.840 --> 0:17:14.359 a very similar process to what we just described with 0:17:14.400 --> 0:17:17.119 the bacteria fighting off of virus, except instead of trying 0:17:17.160 --> 0:17:21.000 to identify a virus and kill the d n A 0:17:21.200 --> 0:17:24.159 so that you don't have to worry about viruses replicating 0:17:24.160 --> 0:17:27.719 inside the cell, what it's looking for is a specific 0:17:27.880 --> 0:17:32.960 strand that relates back to a gene that you want 0:17:33.000 --> 0:17:35.520 to target. So, in other words, we make we can 0:17:35.560 --> 0:17:41.159 manufacture RNA that matches up to a specific gene and 0:17:41.800 --> 0:17:45.040 use the same sort of process. This this dual, these 0:17:45.080 --> 0:17:47.439 dual strands of RNA, one of which is matched to 0:17:47.480 --> 0:17:51.320 the gene to go. Uh, the same sort of thing happens. 0:17:51.320 --> 0:17:54.000 It'll it'll end up using creating the castinine protein that 0:17:54.000 --> 0:17:58.639 will end up unraveling the helix and uh, the RNA 0:17:58.760 --> 0:18:02.400 will bind to with chever gene you specifically want to target, 0:18:02.720 --> 0:18:06.480 and it can snip the ends of the helix exactly 0:18:06.480 --> 0:18:10.000 where you want it, and thus you can isolate a 0:18:10.040 --> 0:18:14.440 specific gene. And it's really not hard to do, yeah, 0:18:14.560 --> 0:18:17.800 especially compared to previous methods. So we we have a 0:18:17.840 --> 0:18:20.800 couple of capabilities here. One of them is the simplest, 0:18:20.840 --> 0:18:23.879 which is just to knockout genes you don't want, right, 0:18:24.000 --> 0:18:27.440 just to see what happens. Yeah, you can like deactivate 0:18:27.440 --> 0:18:30.199 a gene isn't right. So I know we've used an 0:18:30.200 --> 0:18:33.199 analogy to explain genes before, and I'm going to go 0:18:33.240 --> 0:18:35.040 ahead and rely on that again because I think it's 0:18:35.040 --> 0:18:38.760 helpful if you imagine your genes like a giant switchboard, 0:18:39.160 --> 0:18:41.359 and the switches have on and off, So whether a 0:18:41.440 --> 0:18:44.679 gene is on or off determines whether that gene will 0:18:44.760 --> 0:18:48.480 ultimately be expressed. However, it gets a lot more complicated 0:18:48.520 --> 0:18:51.919 from that point forward, right, because it's not always true 0:18:52.000 --> 0:18:55.840 that one gene directly correlates to one trade maybe in 0:18:55.880 --> 0:18:58.399 some cases, but in a lot of cases, you have 0:18:58.600 --> 0:19:03.159 complexes of gene that work together to create complexes of effects, 0:19:03.240 --> 0:19:05.800 and not all of them really go together in a 0:19:05.880 --> 0:19:10.639 logical way. Like I mean, this is a pure imaginative example, 0:19:10.760 --> 0:19:14.040 but it's the equivalent of like how fast your toenails 0:19:14.080 --> 0:19:16.959 grow being connected to your eye color being connected to 0:19:17.800 --> 0:19:20.680 whether or not you get cancer, and and these things 0:19:20.680 --> 0:19:26.160 are really complicated because, uh, nature, because stuff is messy 0:19:26.280 --> 0:19:30.320 and Uh, you know, nothing was really created in our 0:19:30.400 --> 0:19:33.159 gene sequences anticipating that we were going to want to 0:19:33.200 --> 0:19:36.720 go in and just flick switches on and off. So 0:19:37.400 --> 0:19:40.800 nature doesn't owe us an explanation. Yeah. And so in 0:19:40.800 --> 0:19:43.480 other words, isolating these genes and being able to turn 0:19:43.520 --> 0:19:46.479 them off can tell us more about what what is 0:19:46.520 --> 0:19:49.439 the the role of that gene and how does it 0:19:49.480 --> 0:19:53.120 affect the rest of the system. Right, So that that's 0:19:53.119 --> 0:19:56.040 really important information for us to have. Sure, But in 0:19:56.080 --> 0:19:58.920 addition to being able to just knock out and turn 0:19:59.000 --> 0:20:02.920 off specific gene, we could also make changes to genes. Yeah, 0:20:03.320 --> 0:20:06.840 more accurately, I should maybe say changes to the genome. Well, 0:20:06.880 --> 0:20:10.320 and this is important in case you identify a gene 0:20:10.400 --> 0:20:14.200 that's undergone some form of mutation and is not, uh 0:20:14.440 --> 0:20:16.919 the way you would have expected it to be, and 0:20:17.000 --> 0:20:19.679 that it could potentially cause harm, you may wish to 0:20:19.760 --> 0:20:22.119 be able to go in snip that part out and 0:20:22.160 --> 0:20:25.560 replace it with a healthy gene. Right. Okay, Well, we 0:20:25.600 --> 0:20:29.240 now have this system, this Crisper cast nine system for 0:20:29.480 --> 0:20:32.880 editing genes. But this is not the only method there 0:20:32.920 --> 0:20:37.360 has ever been for editing genes. So what makes this 0:20:37.400 --> 0:20:41.080 one an especially big deal? The biggest deal is that 0:20:41.640 --> 0:20:46.520 it's way easier, like like way like way easier. It's 0:20:46.600 --> 0:20:54.280 incredibly precise, efficient, apparently really cost effective and simpler than 0:20:54.440 --> 0:20:58.160 the previous methods that have been employed to do essentially 0:20:58.160 --> 0:20:59.920 the same thing, because it goes about it in a 0:21:00.080 --> 0:21:03.399 very different way, right right, So the two leading types 0:21:03.440 --> 0:21:07.080 of gene editing right now, other than crisper are zinc 0:21:07.200 --> 0:21:11.600 finger nucleases z f ns and transcription activator like effect 0:21:11.640 --> 0:21:16.840 or nucleases or talents talent talents sounds much better than 0:21:16.920 --> 0:21:22.240 ziffens ziffens um. Both both of these depend upon creating 0:21:22.400 --> 0:21:25.119 a thing, a protein, which is what a nuclease is, 0:21:25.720 --> 0:21:28.080 that will bind to the sequence of DNA that you're 0:21:28.119 --> 0:21:31.840 interested in deactivating. So your z fns and your talents 0:21:31.840 --> 0:21:34.800 are only as good as your binding agent. If it's 0:21:34.840 --> 0:21:38.320 not specific enough or not strongly attracted enough to the 0:21:38.359 --> 0:21:41.320 sequence that you're targeting, it won't be very effective and 0:21:41.359 --> 0:21:44.800 could even have dangerous consequences. Like think think of your 0:21:44.800 --> 0:21:48.479 word processors search and replace function. It's really hard to 0:21:48.520 --> 0:21:51.840 create a protein that will bind to the DNA equivalent 0:21:52.000 --> 0:21:56.120 of a whole word like like tomatoes. Okay, if you're 0:21:56.200 --> 0:22:00.520 protein only binds to say tom or toe or toes. 0:22:01.280 --> 0:22:04.199 Then that binding agent could latch onto a lot of 0:22:04.320 --> 0:22:08.640 unintended bits of DNA by accident, which is potentially really 0:22:08.640 --> 0:22:14.440 bad times. Yeah, so very different from those approaches obviously, right, 0:22:14.560 --> 0:22:19.160 So by making this type of gene editing and research 0:22:19.359 --> 0:22:23.560 much faster, easier, more efficient, and in a lot of cases, 0:22:23.640 --> 0:22:27.280 more precise. The positive side is a lot of researchers 0:22:27.280 --> 0:22:29.679 have pointed out that this could speed up research on 0:22:29.760 --> 0:22:34.199 genetic disorders, you know, any inherited genetic condition that we 0:22:34.240 --> 0:22:38.399 want to cure, like cystic fibrosis or muscular dystrophy, you know, 0:22:38.800 --> 0:22:43.800 heritability for a propensity to develop certain cancers, anything like that, 0:22:44.640 --> 0:22:50.280 like like dramatically to a point that's that's almost hard 0:22:50.320 --> 0:22:55.560 to imagine compared to what the progress had been before. Sure, 0:22:55.640 --> 0:23:01.720 the downside is that it's really easy. So it might 0:23:01.760 --> 0:23:05.119 be so easy that we are getting a little bit 0:23:05.119 --> 0:23:09.120 ahead of ourselves and finally could also be the method 0:23:09.240 --> 0:23:13.639 that we use to you know, hack ourselves, like to 0:23:13.640 --> 0:23:17.120 to change things about people. This is the one that's 0:23:17.200 --> 0:23:19.920 raising some alarms, the idea of where we to decide 0:23:19.960 --> 0:23:22.200 we would go down this road right where we Yeah, 0:23:22.320 --> 0:23:24.960 it could potentially go beyond like let's make sure no 0:23:25.000 --> 0:23:27.680 one has cancer and go into like let's make sure 0:23:27.960 --> 0:23:32.800 everyone has the specific visual traits that we want or whatever. 0:23:32.840 --> 0:23:37.080 It is essentially non therapeutic uses for the technology, and 0:23:37.119 --> 0:23:40.080 that's something that could be a future possibility, but it's 0:23:40.119 --> 0:23:43.000 one of those things that raises a lot of ethical questions. 0:23:43.680 --> 0:23:46.160 And now we have to actually start looking at those 0:23:46.160 --> 0:23:50.080 ethical questions because something again that was hypothetical a few 0:23:50.160 --> 0:23:53.000 years ago is now something that could be a reality 0:23:53.160 --> 0:23:55.800 maybe a few years from now. Ah. Yeah. And it's 0:23:55.800 --> 0:23:59.919 not just you know, lay people who are disinterested in 0:24:00.040 --> 0:24:02.960 science as a whole who are freaked out about this. No, 0:24:03.119 --> 0:24:07.480 there are actual scientists who are legitimately concerned about this. Yeah. 0:24:07.480 --> 0:24:12.280 There have been at least two high profile calls from 0:24:12.280 --> 0:24:15.359 scientists in the past month or so, well, in the 0:24:15.400 --> 0:24:17.960 past month from the time we're recording this, which one 0:24:18.040 --> 0:24:23.080 which is April. Yeah, so in uh March March twelve 0:24:23.480 --> 0:24:26.680 between a group of scientists published a comment in Nature 0:24:27.600 --> 0:24:31.240 basically calling for a moratorium on editing the human germ line. 0:24:31.520 --> 0:24:34.679 And this is a specific, uh specific portion of the 0:24:34.720 --> 0:24:37.119 application of crisper. They're they're they're not saying like like 0:24:37.240 --> 0:24:41.439 hall Doll, Crisper forever um. The human germ line is 0:24:41.480 --> 0:24:46.919 specifically human reproductive cells that can pass on heritable traits. 0:24:47.560 --> 0:24:51.400 It can it can lead to changes in generations down 0:24:51.480 --> 0:24:54.280