WEBVTT - Is It Safe to Edit Your DNA? 0:00:00.200 --> 0:00:02.400 Hey, please take a second and leave us a review 0:00:02.480 --> 0:00:06.279 on Apple Podcasts, Spotify, or wherever you listen to the podcast. 0:00:06.960 --> 0:00:11.080 Thanks a lot. Hey, welcome to Sign Stuff or production 0:00:11.240 --> 0:00:14.320 of iHeart Radio. I'm Jorge cham and today we're answering 0:00:14.360 --> 0:00:18.239 the question is it safe to edit your DNA? In 0:00:18.280 --> 0:00:20.520 case you haven't been keeping up, humans now have the 0:00:20.560 --> 0:00:25.160 ability to change their genes. You could, for example, take 0:00:25.200 --> 0:00:28.120 a pill that will change the DNA of your eyes, 0:00:28.600 --> 0:00:33.000 or your skin, or even your brain. And it's all 0:00:33.080 --> 0:00:37.639 due to a technology called Crisper. But how far can 0:00:37.680 --> 0:00:41.680 we take this technology? Is it safe or even ethical 0:00:41.760 --> 0:00:44.880 to use. We're gonna talk to two geneticists who work 0:00:44.960 --> 0:00:47.800 with Crisper, and we're gonna learn where it came from 0:00:48.040 --> 0:00:51.279 and how it works. So start thinking about how you 0:00:51.320 --> 0:00:55.080 would upgrade yourself and edit your genes as we answer 0:00:55.120 --> 0:01:03.080 the question is it safe to edit your DNA? Hey? Everyone, 0:01:03.400 --> 0:01:05.720 I don't know about you, but sometimes I feel like 0:01:05.840 --> 0:01:09.960 the future arrived and I wasn't paying attention. I mean, 0:01:10.000 --> 0:01:12.319 it seems like yesterday to me that we were able 0:01:12.360 --> 0:01:15.920 to sequence the human genome, and now apparently we can 0:01:15.959 --> 0:01:20.280 basically edit it as easily as editing a word. Document. 0:01:20.560 --> 0:01:22.319 If you don't like the gene that you have inside 0:01:22.319 --> 0:01:25.160 of you, you can just cut it and paste it. 0:01:25.560 --> 0:01:27.399 So I had a lot of catching up to do. 0:01:27.720 --> 0:01:29.959 And so before we get to the question of whether 0:01:30.040 --> 0:01:32.920 it's safe to edit your DNA, we're gonna learn where 0:01:32.920 --> 0:01:36.640 this technology came from and how it works, because to 0:01:36.760 --> 0:01:40.319 understand its limits and what makes it potentially dangerous, we're 0:01:40.360 --> 0:01:43.120 gonna eat both of those things. And the history of 0:01:43.120 --> 0:01:46.160 how crisper came to be is actually kind of interesting. 0:01:46.560 --> 0:01:49.040 It all started in a small lab in the south 0:01:49.080 --> 0:01:53.480 of Spain that was looking at tiny creatures called Archaea. 0:01:53.880 --> 0:01:58.280 To Phillisen. Here's Professor Louis Montealieu, a geneticist and the 0:01:58.320 --> 0:02:05.880 deputy director of Spain International Center for Biotechnology in Madrid. Well, 0:02:05.880 --> 0:02:07.600 thank you, doctor Montaliu for joining us. 0:02:08.080 --> 0:02:08.400 Thank you. 0:02:08.960 --> 0:02:11.720 So we have a very general audience who may not 0:02:11.800 --> 0:02:14.840 have heard of crisper or even gene editing. So for 0:02:15.040 --> 0:02:17.400 people who are not familiar, can you tell us about 0:02:17.520 --> 0:02:20.640 the history of gene editing. When did this idea start 0:02:20.760 --> 0:02:22.359 becoming a reality for people? 0:02:22.880 --> 0:02:26.480 Well, genomeediting is one of these revolutions you never know 0:02:26.800 --> 0:02:30.000 that you will be able to winness so this are 0:02:30.080 --> 0:02:36.480 tool that enable precise genetic modification of georgenome and as 0:02:36.480 --> 0:02:40.960 a matter of fact, any genome of any creature, any bacteria, 0:02:40.960 --> 0:02:44.040 any plan and including human beings. At the end of 0:02:44.160 --> 0:02:48.040 the previous century we had a first generation of geno 0:02:48.120 --> 0:02:52.520 mediating Those were called megan nucleases that were not very versatile, 0:02:52.880 --> 0:02:55.720 so they were not used much. Then we had two 0:02:55.840 --> 0:02:59.480 different families of geneo mediting tools, and for some time 0:02:59.600 --> 0:03:03.440 there were okay, but the real revolution came across when 0:03:03.560 --> 0:03:08.560 we discover crispa. Crispa is an acronym for a cluster. 0:03:08.919 --> 0:03:11.239 Let me see I have it here because we always say, 0:03:11.440 --> 0:03:15.120 say chrispa, and we always forget this by is cluster 0:03:15.320 --> 0:03:18.160 regularly interspace short palindromic rapids. 0:03:18.320 --> 0:03:20.519 The acronym is too catchy, it's too easy. 0:03:20.560 --> 0:03:23.080 It is very sexy exactly so it looks like what 0:03:23.160 --> 0:03:28.720 you're having for breakfast, chrispher from Kellos and Crispa was invented, 0:03:28.760 --> 0:03:32.040 by the way, by one the young microbiologist at the 0:03:32.160 --> 0:03:35.960 University of Licante at the south of Spain. So the 0:03:36.000 --> 0:03:39.240 origin of crispa, it's actually in Spain, and this is 0:03:39.280 --> 0:03:40.200 normally forgotten. 0:03:41.480 --> 0:03:44.520 Okay, So to get to the origin of this revolutionary technology, 0:03:44.680 --> 0:03:46.920 we have to go back even further than the turn 0:03:47.080 --> 0:03:50.080 of the millennium. Back in nineteen ninety three, a young 0:03:50.120 --> 0:03:54.160 researcher in Spain called Francis Mohika was interested in something 0:03:54.480 --> 0:03:57.560 very few people thought was important and that was completely 0:03:57.680 --> 0:04:01.480 unrelated to gene editing. He wanted to know how a 0:04:01.600 --> 0:04:05.040 very primitive form of life called urkia, which are kin 0:04:05.120 --> 0:04:08.840 of the cousins of bacteria, could survive in super salty 0:04:08.920 --> 0:04:12.480 pools of water. So he did what everyone was doing 0:04:12.560 --> 0:04:15.480 in the early nineteen nineties, which was to sequence the 0:04:15.600 --> 0:04:18.680 DNA of these supers dirty or KaiA to see if 0:04:18.680 --> 0:04:21.040 there were any clues there. But when he looked at 0:04:21.040 --> 0:04:23.760 their DNA, he noticed something odd. 0:04:25.320 --> 0:04:29.000 He saw repetitions the same sequence, same shot sequence, repeated 0:04:29.080 --> 0:04:32.719 many times. That was his discovery in nineteen ninety three, 0:04:33.640 --> 0:04:35.320 and this puzzled Mohika. 0:04:35.400 --> 0:04:38.560 Why did these archaia have this stretch of genetic code 0:04:38.839 --> 0:04:41.800 all over its DNA? And while you and I might 0:04:41.880 --> 0:04:44.400 just shrug this off and move on with our lives, 0:04:44.640 --> 0:04:47.920 Mohika spent the next ten years of his life trying 0:04:48.000 --> 0:04:48.920 to figure it out. 0:04:49.400 --> 0:04:54.240 And he did, and it took him about ten years 0:04:54.320 --> 0:04:58.080 to discover by someow of two thousand and three that 0:04:58.160 --> 0:05:01.640 this was the basis of an immune system, of a 0:05:01.720 --> 0:05:06.720 defence system the bacterias were using to fight the viruses. 0:05:07.839 --> 0:05:11.719 Yes, even bacteria and primitive organisms like archaea have to 0:05:11.800 --> 0:05:15.799 fight viruses. What Uhika found was that the repeating sequence 0:05:15.839 --> 0:05:19.560 of DNA was part of a pretty badass system for 0:05:19.720 --> 0:05:23.600 killing viruses. Here's how it works. Whenever a virus attacks 0:05:23.640 --> 0:05:27.000 the Arkaia and the Archaea survives, it grabs a piece 0:05:27.040 --> 0:05:31.080 of the virus DNA and remembers it. It stores the 0:05:31.080 --> 0:05:35.080 little virus sequence in its own DNA. 0:05:35.200 --> 0:05:39.160 So the bacterias that have been visited by many viruses 0:05:39.200 --> 0:05:42.920 over thousands or hundreds of millions of years, they had 0:05:43.040 --> 0:05:47.120 bits and bits and bits of different viral genomes and 0:05:47.200 --> 0:05:50.400 this was like a picture they kept from the virus. 0:05:50.400 --> 0:05:54.039 So next time the same viruses wanted to infect this bacteria, 0:05:54.080 --> 0:05:57.120 they say, hey, I know you, I know who you are, 0:05:57.440 --> 0:05:59.560 and because I know who you are, I can fight 0:05:59.680 --> 0:06:01.720 you and I can destroy your DNA. 0:06:03.120 --> 0:06:07.720 So the Arkaea or bacteria remember every single virus they've 0:06:07.720 --> 0:06:11.680 ever interacted with, and they lay a trap for them. 0:06:11.920 --> 0:06:16.799 They create a molecule called CAS nine or CAST nine, 0:06:17.120 --> 0:06:20.680 which is basically like a sharp DNA scissor, And to 0:06:20.720 --> 0:06:23.359 each copy of this scissor they give it the memory 0:06:23.480 --> 0:06:26.920 of each virus they've ever met. So now the archaea 0:06:27.080 --> 0:06:30.240 has a bunch of scissors rooting around, each of them 0:06:30.400 --> 0:06:33.960 keyed to a snippet of the DNA of every virus 0:06:34.040 --> 0:06:37.000 it's ever encountered. You can start to see how this 0:06:37.040 --> 0:06:41.919 could be used to cut your own DNA. 0:06:42.120 --> 0:06:46.520 This is a very efficient system that was invented by bacterias. 0:06:47.120 --> 0:06:50.720 This was invented probably more than three billion years ago, 0:06:51.080 --> 0:06:54.880 so this is something that has been drunning for many years. 0:06:55.040 --> 0:06:58.400 So next time a virus wants to insert the DNA, 0:06:58.960 --> 0:07:02.680 if the virul is known by the lacteria, this will 0:07:02.720 --> 0:07:06.120 trigger a signal and the signal will start cutting the 0:07:06.200 --> 0:07:08.920 viral DNA. And if you cut the vital DNA, basically 0:07:09.080 --> 0:07:12.680 you destroy They may that you destroy the intruth. 0:07:14.480 --> 0:07:18.040 All right. This was a discovery that eventually led to Crisper. 0:07:18.720 --> 0:07:22.000 These Archaia and bacteria basically figured out how to make 0:07:22.040 --> 0:07:25.040 a DNA scissor, and they figured out how to key 0:07:25.120 --> 0:07:29.280 the scissor to a particular sequence of DNA, So the 0:07:29.280 --> 0:07:33.480 scissors are floating around looking for a particular stretch of DNA. 0:07:33.840 --> 0:07:36.920 When it finds, it cuts the DNA, but only in 0:07:36.960 --> 0:07:40.480 the spot where it finds the sequence. Now, at first, 0:07:40.680 --> 0:07:43.640 nobody thought this could be used at a DNA. It 0:07:43.800 --> 0:07:46.920 was just some discovery about the immune system of bacteria, 0:07:47.440 --> 0:07:50.600 and in fact, Mohika had trouble getting it polished. 0:07:52.600 --> 0:07:57.200 He submitted this discovery to the top journal's Nature Science 0:07:57.280 --> 0:08:02.080 Cell and they all rejected because what really they all 0:08:02.120 --> 0:08:05.440 rejected because this was coming from Alicante, was not coming 0:08:05.440 --> 0:08:09.160 from Stanford, from Yale, from Oxborg, Cambridge, so he didn't 0:08:09.200 --> 0:08:12.880 include any kind of foreign researcher. It was him with 0:08:13.320 --> 0:08:17.320 his students, and eventually he took him like two years, 0:08:17.360 --> 0:08:20.840 and in two thousand and five he published his discovery 0:08:21.000 --> 0:08:25.360 in a very historical journal, but kind of very far 0:08:25.400 --> 0:08:29.200 away from the top journals. The journal was a journal 0:08:29.240 --> 0:08:32.320 of molecular evolution, all. 0:08:32.280 --> 0:08:35.640 Right, So Mohika publishes this in a not so prominent journal, 0:08:36.040 --> 0:08:37.920 and that could have been the end of the story. 0:08:38.280 --> 0:08:40.600 Maybe nobody would have read it or thought it could 0:08:40.600 --> 0:08:44.480 be used for anything other than understanding how bacteria work. 0:08:45.280 --> 0:08:48.200 But the two special people happened to read the paper 0:08:48.760 --> 0:08:50.400 and they had an idea. 0:08:51.720 --> 0:08:54.319 What happens since that that paper in two thousand and 0:08:54.400 --> 0:08:58.199 five was read by many other people. Jennifer Downa and 0:08:58.240 --> 0:09:03.280 Emmanuel Charpantier, and these two working independently, they met in 0:09:03.400 --> 0:09:07.520 San Juana, Puerto Rico in spring of twenty and eleven 0:09:08.000 --> 0:09:11.960 and they decided to collaborate because they both have read 0:09:12.040 --> 0:09:15.920 Francis paper that was published like six years before, and 0:09:16.000 --> 0:09:21.079 they had the idea to transform this defense system into 0:09:21.120 --> 0:09:24.720 a genomediting tool, into a tool that you could use 0:09:24.840 --> 0:09:28.480 to eraise and to replace letters so in order to 0:09:28.600 --> 0:09:32.480 correct mutations. And that's exactly what they decided to do. 0:09:32.600 --> 0:09:35.559 And it took them only one year to do this collaboration, 0:09:35.679 --> 0:09:38.000 and that's the only time they collaborated. They never have 0:09:38.440 --> 0:09:42.520 collaborated again. And they published this in Science and eight 0:09:42.600 --> 0:09:46.800 years later, in October twenty twenty, they were awarded a 0:09:46.880 --> 0:09:48.720 Nobel Prize of Chemistry. 0:09:50.040 --> 0:09:53.000 And that's how we got Crisper. From a scientists getting 0:09:53.040 --> 0:09:56.880 curious about how bacteria basically survive a cold, we get 0:09:56.920 --> 0:09:59.959 to a Nobel price and a technology that might revel 0:10:00.040 --> 0:10:03.040 uianized medicine, and even who we are. 0:10:04.640 --> 0:10:08.760 And the beauty of this is that this was basic science. 0:10:09.120 --> 0:10:14.200 So when he was discovering how bacteria fight viruses, nobody cared. 0:10:14.440 --> 0:10:17.000 He said, what is this? Who is interested how the 0:10:17.040 --> 0:10:21.200 bacteria decide to fight viruses? Well, what happens is that 0:10:21.679 --> 0:10:25.600 the same mechanism that is used by bacteria to fight 0:10:25.800 --> 0:10:31.240 viruses is what Manuel Chaptee and Jennifer Downer transformed into 0:10:31.280 --> 0:10:37.400 a genomeedicing tour. Basic science became an application many years later, 0:10:37.800 --> 0:10:41.080 I think, and this is the poetry behind these ideas, 0:10:41.320 --> 0:10:45.160 because he was sharing his knowledge about what the bacterias 0:10:45.160 --> 0:10:48.920 are capable of doing, and then that was illominating new 0:10:48.960 --> 0:10:52.360 ideas in the mind of all the researchers many years later. 0:10:53.480 --> 0:10:55.160 All right, when we come back, we're going to talk 0:10:55.200 --> 0:10:58.520 to another scientist about how crisper actually works to edit 0:10:58.559 --> 0:11:01.480 your DNA, what you can do with it, and then 0:11:01.559 --> 0:11:04.520 later we'll talk about whether it's safe to edit your 0:11:04.600 --> 0:11:09.480 DNA or even morally right, So stay with us. We'll 0:11:09.520 --> 0:11:24.840 be right back, and we're back. We're talking about whether 0:11:24.920 --> 0:11:27.960 it's safe to edit your DNA, and the main way 0:11:28.000 --> 0:11:31.280 scientists and doctors are doing this is with a technology 0:11:31.320 --> 0:11:35.600 called Crisper, which we learn is what most archaea and 0:11:35.640 --> 0:11:40.439 about half of all bacteria use to defend themselves against viruses. 0:11:41.240 --> 0:11:44.240 But around twenty twelve scientists figure it out it could 0:11:44.280 --> 0:11:48.040 be used for gene editing. Now, the basic idea of 0:11:48.080 --> 0:11:51.800 crisper is this, there's a special kind of molecule that 0:11:52.000 --> 0:11:56.040 acts like a scissor to DNA, meaning it can cut 0:11:56.200 --> 0:11:59.760 strands of DNA. But there's a way to attach as 0:12:00.040 --> 0:12:03.200 nippit of genetic code to this scissor, so that the 0:12:03.200 --> 0:12:06.559 scissor will only cut in the places where it sees 0:12:06.679 --> 0:12:11.280 the nippet in the DNA strand. It's like imagine if 0:12:11.320 --> 0:12:13.560 you have a book and you only wanted to cut 0:12:13.600 --> 0:12:16.880 the book in places where it had the word hippopotamus 0:12:17.040 --> 0:12:20.439 printed on it. Well, you would print the word hippopotamus 0:12:20.559 --> 0:12:23.160 on a little strip of paper, and you'd attach this 0:12:23.280 --> 0:12:26.479 strip to a special kind of scissors, and the scissors 0:12:26.600 --> 0:12:29.480 would check every word on the book, and whenever it 0:12:29.520 --> 0:12:33.440 saw the word hippopotamus, it would cut the page, breaking 0:12:33.640 --> 0:12:36.880 the flow of words. Now, the question is how do 0:12:36.960 --> 0:12:41.720 you use this to edit human DNA and is it safe. 0:12:42.120 --> 0:12:44.839 To help explain how crisper works, I reached out to 0:12:44.920 --> 0:12:48.920 doctor Leanna Pelea, a researcher at the University of Zurich 0:12:49.120 --> 0:12:51.560 and one of the co authors of a well cited 0:12:51.559 --> 0:12:55.760 paper on Crisper titled Past, Present and Future of Crisper 0:12:55.960 --> 0:12:59.680 Genome Editing Technologies. Thank you so much, doctor Pellia. 0:12:59.720 --> 0:13:02.079 For Joe, thank you so much for having me. It's 0:13:02.120 --> 0:13:02.960 really a pleasure. 0:13:04.280 --> 0:13:07.240 According to doctor Peleia, in just the last ten or 0:13:07.280 --> 0:13:12.319 twelve years, there have already been three generations of Crisper technologies, 0:13:12.640 --> 0:13:15.480 and each one is more advanced than the last. It's 0:13:15.520 --> 0:13:17.640 sort of like the iPhone. 0:13:19.120 --> 0:13:22.280 Because I think Krisper twos are a bit like the iPhone. 0:13:22.400 --> 0:13:24.120 It's always like a newer version. 0:13:26.520 --> 0:13:28.040 Each one has a better camera. 0:13:28.440 --> 0:13:31.880 Yes, it's a better camera, better features, and it's always 0:13:31.880 --> 0:13:33.520 getting better. It's very exciting. 0:13:34.360 --> 0:13:36.200 Okay, we're going to talk about what each of these 0:13:36.240 --> 0:13:39.400 generations that Chrisper can do, because that's going to help 0:13:39.480 --> 0:13:42.840 us when we talk about what makes these technologies risky. 0:13:43.440 --> 0:13:47.640 Here's how doctor Pellia describes what we'll call Crisper one 0:13:47.720 --> 0:13:48.439 point zero. 0:13:50.000 --> 0:13:53.439 Yes, so the original Chrispher systems are just Cast nine 0:13:53.559 --> 0:13:56.880 or Cast TWELVEA. They cut both strands of DNA, so 0:13:56.920 --> 0:13:59.920 in human sales the DNA. We know it's like double stranded, 0:14:00.360 --> 0:14:03.319 which means it has two strands of DNA, and these 0:14:03.440 --> 0:14:06.440 enzyme cut both the top and the bottom strand of 0:14:06.520 --> 0:14:10.559 the DNA. So by producing double strand break, meaning cutting 0:14:10.600 --> 0:14:13.520 both strands of the DNA, that means that the cells 0:14:13.679 --> 0:14:17.520 undergo damage into their DNA. So when there is a 0:14:17.600 --> 0:14:20.440 double strand break, a dour gene of interest, the DNA 0:14:20.520 --> 0:14:24.080 repair mechanism, that is something that the human cells have 0:14:24.280 --> 0:14:27.920 by themselves, would fix the brake. And in fixing the brake, 0:14:28.080 --> 0:14:31.760 it's going to introduce some small mutations. And in this 0:14:31.960 --> 0:14:35.840 way we can disrupt the activity of human genes, which 0:14:35.880 --> 0:14:37.480 is something that's very useful. 0:14:39.680 --> 0:14:43.880 Okay, So Crisper one point zero is essentially a gene breaker. 0:14:44.240 --> 0:14:46.200 Let's say you have a gene in your DNA that 0:14:46.280 --> 0:14:49.320 has mutated or a gene that you inherited that is 0:14:49.360 --> 0:14:53.320 giving you a disease. For example, sickle cell disease, which 0:14:53.360 --> 0:14:56.520 affects about one hundred thousand people in the US, can 0:14:56.560 --> 0:14:59.840 be traced to a single mutation in your DNA that 0:15:00.000 --> 0:15:03.320 it causes red blood cells to have the wrong shape. 0:15:03.560 --> 0:15:06.320 So to cure this disease, you want to take out 0:15:06.320 --> 0:15:09.160 this gene, Well, you can do it with Crisper by 0:15:09.160 --> 0:15:11.840 writing down this gene in that little piece of paper 0:15:11.880 --> 0:15:15.400 I described before attaching it to the cutting molecule that 0:15:15.600 --> 0:15:18.760 acts like a scissor, and then letting these scissors loose 0:15:19.000 --> 0:15:22.880 on the patient's bone marrows themselves. The scissors will then 0:15:23.000 --> 0:15:27.400 find this gene in the DNA sequence and cut the gene. Now, 0:15:27.560 --> 0:15:31.600 human DNA has a self prepaired mechanism that would normally 0:15:31.640 --> 0:15:35.560 fix this cut. But this mechanism is not perfect. Every 0:15:35.560 --> 0:15:40.280 once in a while it makes a mistake. But if 0:15:40.320 --> 0:15:43.280 the human body fixes the break, doesn't that defeat the 0:15:43.280 --> 0:15:45.280 purpose of knocking out the gene. 0:15:45.920 --> 0:15:49.000 So that's the thing. So the human body fixes the break, 0:15:49.080 --> 0:15:52.600 but it doesn't fix it perfectly. Sometimes it could fix 0:15:52.640 --> 0:15:55.600 it properly. But even if it's fixed properly, then it's 0:15:55.640 --> 0:15:58.800 going to be cut again by another cast nine molecule 0:15:59.040 --> 0:16:01.440 and cut again and again, so in the end it's 0:16:01.520 --> 0:16:05.640 going to be probably mutated. So that would cause disruption 0:16:05.760 --> 0:16:06.440 of the gene. 0:16:07.320 --> 0:16:10.680 So Crisper will cut the DNA. Then the DNA will 0:16:10.720 --> 0:16:14.920 repair itself, so Crisper will cut it again, and this 0:16:15.000 --> 0:16:19.160 will repeat until the repair mechanism makes a mistake, and 0:16:19.200 --> 0:16:21.760 so you'll end up with a different version of the gene. 0:16:22.120 --> 0:16:25.360 And because it's different, it's not going to work. And 0:16:25.400 --> 0:16:28.200 because it doesn't work, the patient is not going to 0:16:28.240 --> 0:16:32.200 have the disease anymore. So that's level one of editing 0:16:32.240 --> 0:16:35.800 your DNA. You can basically kill a gene and this 0:16:35.880 --> 0:16:38.840 has been shown to work in people. After about nine 0:16:38.920 --> 0:16:42.760 years of research and pre clinical trials and clinical studies, 0:16:43.080 --> 0:16:47.440 the FDA in December twenty twenty three approved the use 0:16:47.480 --> 0:16:51.560 of Crisper for treating sickle cell disease. Okay, now we 0:16:51.600 --> 0:16:54.120 move on to Crisper two point zero. 0:16:55.240 --> 0:16:58.760 Yeah, so the second generation involved in engineer risper and 0:16:58.880 --> 0:17:02.160 so and these enzyme is engineered so it cannot cut 0:17:02.200 --> 0:17:05.120 both strands of DNA, but they can only cut one 0:17:05.280 --> 0:17:08.320 of the DNA strands. Okay, And instead of making a 0:17:08.359 --> 0:17:12.200 double strand DNA break, they make a single strand DNA break. 0:17:12.400 --> 0:17:15.160 And this is less toxic than the double strand break. 0:17:15.480 --> 0:17:19.520 I see, because the cell doesn't freak out as much. Yes, okay, 0:17:19.520 --> 0:17:21.640 so then how does it work? It breaks one strand? 0:17:21.920 --> 0:17:24.960 Yeah, it breaks one strand. But that's not all they do. 0:17:25.040 --> 0:17:28.320 So they are also fews with an enzyme called damnas, 0:17:28.640 --> 0:17:32.719 which could convert one DNA letter to another, So it 0:17:32.960 --> 0:17:36.359 makes the letter change on the strand that it doesn't break. 0:17:37.440 --> 0:17:40.399 Okay, this is where we get to actual gene editing. 0:17:40.880 --> 0:17:44.399 The first of the second generation of Chrisper tools, called 0:17:44.560 --> 0:17:48.720 base editing, goes in, breaks one strand of DNA and 0:17:48.760 --> 0:17:53.119 then replaces one letter in your DNA sequence. So before 0:17:53.240 --> 0:17:58.280 if your gene read something like ATTAGC, it might now 0:17:58.320 --> 0:18:06.400 read adt cgc. Wow. So now this tool has two things, 0:18:06.600 --> 0:18:10.760 the cutter and something that it replaces one letter. 0:18:11.480 --> 0:18:16.080 Yes. So these are very powerful for maybe correcting mutations 0:18:16.080 --> 0:18:18.480 that are just defecting one letter. 0:18:18.920 --> 0:18:21.760 Okay, that's base editing, and you said there was another one. 0:18:21.920 --> 0:18:25.919 Yes, that's prime editing, where this technology makes also a 0:18:25.960 --> 0:18:29.719 single strand break off the DNA and then it extends 0:18:29.840 --> 0:18:33.440 one of the DNA strands with a new sequence of interest. 0:18:33.920 --> 0:18:38.359 And depending on how these prime editors are engineered, one 0:18:38.400 --> 0:18:42.720 could make up to maybe one hundred nucleotide modifications into 0:18:42.760 --> 0:18:43.400 the genome. 0:18:43.720 --> 0:18:46.080 And when you say one hundred nickelodies, you mean like 0:18:46.119 --> 0:18:47.680 one hundred letters in your DNA. 0:18:47.760 --> 0:18:50.280 One hundred letters of DNA. You could add up to 0:18:50.359 --> 0:18:54.320 a hundred letters and also delete something in the ten 0:18:54.800 --> 0:18:56.000 two hundred range. 0:18:56.960 --> 0:19:00.280 All right, now we're getting even more advanced. What can 0:19:00.480 --> 0:19:05.160 the second generation Crisper tools called prime editing, can go in, 0:19:05.520 --> 0:19:09.560 cut your DNA and replace up to one hundred letters 0:19:09.600 --> 0:19:12.560 in your DNA sequence, and then we get to Crisper 0:19:12.800 --> 0:19:14.000 three point zero. 0:19:16.160 --> 0:19:19.520 You know, with first generation and second generation, these are 0:19:19.640 --> 0:19:22.919 very powerful, but the range of the mutations that they 0:19:22.960 --> 0:19:26.879 can make are still relatively small. So if we imagine 0:19:27.040 --> 0:19:31.320 different patients and they all have mutations in a certain gene, 0:19:31.440 --> 0:19:34.760 maybe some patients would have a mutations more towards the 0:19:34.840 --> 0:19:38.159 beginning of the gene, some patients more towards the end 0:19:38.280 --> 0:19:40.960 of the gene, some patients more in the middle of 0:19:41.000 --> 0:19:44.920 the gene. And with these first and second generation tools, 0:19:44.960 --> 0:19:48.320 in general, we would need a different correction strategy for 0:19:48.520 --> 0:19:51.640 different parts of a gene. But that's where the third 0:19:51.680 --> 0:19:55.399 generation tools come into place, where you could have large 0:19:55.480 --> 0:19:59.439 insertions into the genome and you could insert gene size 0:19:59.520 --> 0:20:03.200 fragments where in theory you could replace the whole mutant 0:20:03.280 --> 0:20:04.840 gene with the correct version. 0:20:06.440 --> 0:20:10.399 So Crisper three point oh can replace whole genes at 0:20:10.400 --> 0:20:13.680 a time, that's like being able to edit several pages 0:20:13.760 --> 0:20:17.040 in a book and not just one letter or a paragraph. 0:20:17.359 --> 0:20:20.639 And scientists are even working on Crisper four point zh. 0:20:20.960 --> 0:20:24.240 Well not technically Crisper four point oh, because these new 0:20:24.280 --> 0:20:27.080 tools use a different system than Crisper, but they work 0:20:27.200 --> 0:20:28.000 the same way. 0:20:29.040 --> 0:20:33.840 Then we have an emerging class of engineer gcombinaces. This 0:20:34.000 --> 0:20:36.800 is a bit complicated, but these enzymes allow us to 0:20:36.880 --> 0:20:41.080 make large deletions in the genome, large inversions, and large 0:20:41.119 --> 0:20:44.440 insertions in the same time. I think at this point 0:20:44.640 --> 0:20:47.959 we could make megabased mutations. 0:20:47.640 --> 0:20:50.000 Like a million letters. So we're at the point where 0:20:50.000 --> 0:20:53.040 we can change millions of letters at a time. Yes, 0:20:53.200 --> 0:20:56.320 So then what's the next step to change whole chromosomes 0:20:56.320 --> 0:20:57.040 and things like that? 0:20:57.280 --> 0:20:59.200 Yeah, I don't know, Like we are waiting. I think 0:20:59.200 --> 0:21:01.040 that would be quite interesting for sure. 0:21:01.320 --> 0:21:04.200 Okay, well, we're at the stage where we're waiting for 0:21:04.320 --> 0:21:08.879 Tim Cook to announce when the next generation of iPhones 0:21:08.920 --> 0:21:11.719 are Yes, do you have to stand in line at 0:21:11.720 --> 0:21:13.920 the Apple store for a really long time, I'll say, 0:21:14.080 --> 0:21:14.359 or no. 0:21:15.280 --> 0:21:15.639 Yes. 0:21:16.520 --> 0:21:19.440 So basically we're almost at the point where we can 0:21:19.560 --> 0:21:23.399 change anything about our DNA. You're not happy with the 0:21:23.480 --> 0:21:26.679 genes you inherit it from your parents. You could, in theory, 0:21:27.200 --> 0:21:29.720 just cut and pay some new genes. But now the 0:21:29.800 --> 0:21:33.359 question is it safe to do this? What are the 0:21:33.480 --> 0:21:37.320 risks of this technology, and maybe more important, is it 0:21:37.520 --> 0:21:41.640 right to change your DNA? When we come back, we'll 0:21:41.680 --> 0:21:45.120 dig into the risks of using Crisper and the ethics 0:21:45.160 --> 0:21:49.840 of gene editing. Stay with us, you're listening to science stuff, 0:22:02.480 --> 0:22:06.199 and we're back. We're talking about whether it's safe to 0:22:06.359 --> 0:22:10.040 edit or change your DNA, which is a relatively new 0:22:10.119 --> 0:22:13.560 question in the history of humanity. As we learn from 0:22:13.560 --> 0:22:16.040 our experts, we are getting close to the point where 0:22:16.080 --> 0:22:19.480 we can alter our genes in almost any way we want. 0:22:20.040 --> 0:22:22.560 And all of this has only recently come up with 0:22:22.600 --> 0:22:26.359 a new technology called Crisper. Now the question is is 0:22:26.400 --> 0:22:30.399 it safe to change your DNA. Here's how doctor Juana 0:22:30.480 --> 0:22:34.439 Pella answers that question. Now, maybe step me through it. 0:22:34.600 --> 0:22:39.000 Let's say I want to have blue eyes. Okay, what 0:22:39.080 --> 0:22:40.040 would be the first step? 0:22:40.560 --> 0:22:43.800 Well, I don't think that we are there yet to 0:22:43.960 --> 0:22:48.080 make you know, genome edits for these kind of features. 0:22:48.320 --> 0:22:52.600 We can edit DNA, but this comes with certain limitations 0:22:52.640 --> 0:22:56.640 and certain problems. That are actually associated with these Yeah, 0:22:56.680 --> 0:23:01.040 we can edit DNA associated with certain diseases, but we 0:23:01.119 --> 0:23:04.320 take this risk because the benefit of editing the DNA 0:23:04.880 --> 0:23:09.480 outweighs the problems caused by this disease. And having blue eyes, 0:23:09.600 --> 0:23:12.040 I mean, I don't know. I think maybe easiest is 0:23:12.080 --> 0:23:16.159 to get contact lenses that blue eyes. 0:23:18.400 --> 0:23:20.280 That does sound easier, Yeah, it does. 0:23:20.520 --> 0:23:24.080 I don't think that at the moment, like the benefits 0:23:24.160 --> 0:23:28.040 of having blue eyes with gene editing would justify this. 0:23:29.119 --> 0:23:32.040 What Tarcapilla is saying is that there are still risks 0:23:32.080 --> 0:23:35.560 in editing your DNA, so at the moment, you probably 0:23:35.640 --> 0:23:38.480 don't want to use it for something as trivial as 0:23:38.640 --> 0:23:42.520 changing your eye color. Okay, what are these risks? Well, 0:23:42.600 --> 0:23:46.240 there are three things that can go wrong when using crisper. 0:23:46.720 --> 0:23:49.879 The first is that crisper might cut your DNA in 0:23:50.040 --> 0:23:53.840 places that you don't want it to cut. I heard 0:23:53.840 --> 0:23:57.680 that one of the risks in gene editing is that 0:23:57.840 --> 0:24:01.000 the guide sequence is made to match a certain part 0:24:01.040 --> 0:24:03.680 of your DNA, but it's possible that the same sequence 0:24:03.680 --> 0:24:05.400 exists somewhere else in your DNA. 0:24:05.760 --> 0:24:08.720 I think this is for sure one of the major 0:24:08.760 --> 0:24:13.000 problems there might be similar sequences in other parts of 0:24:13.040 --> 0:24:13.640 the genome. 0:24:15.160 --> 0:24:17.960 Remember that the way crisper works is that you attach 0:24:18.160 --> 0:24:21.919