1 00:00:04,280 --> 00:00:07,240 Speaker 1: Get in test with technology with tex Stuff from how 2 00:00:07,320 --> 00:00:14,760 Speaker 1: stuff works dot com. Hey there, we one, and welcome 3 00:00:14,800 --> 00:00:17,800 Speaker 1: to tech Stuff. I'm Jonathan Strickland and I'm luring voc 4 00:00:17,840 --> 00:00:21,800 Speaker 1: Obama and today we've got our topic courtesy of a 5 00:00:21,920 --> 00:00:26,120 Speaker 1: listener request. Yes, this is listener Mike via Twitter. I 6 00:00:26,160 --> 00:00:29,000 Speaker 1: didn't write down his screen name, so one of the 7 00:00:29,040 --> 00:00:31,840 Speaker 1: Mike's on Twitter, thank you sir yea and said, have 8 00:00:31,880 --> 00:00:34,240 Speaker 1: you done a podcast on gene therapy? Is that something 9 00:00:34,280 --> 00:00:37,519 Speaker 1: that at Blow the Mind would do instead? That's a 10 00:00:37,880 --> 00:00:41,280 Speaker 1: stuff to blow your mind. That's the Julie Robert Julie 11 00:00:41,320 --> 00:00:45,360 Speaker 1: doing their their science podcast, and we really we've talked 12 00:00:45,400 --> 00:00:48,800 Speaker 1: about gene therapy a little bit on Tech Stuff in 13 00:00:48,840 --> 00:00:51,000 Speaker 1: the past, we've never done a full episode on it. 14 00:00:51,000 --> 00:00:53,720 Speaker 1: We've also talked about it on a sister podcast, the 15 00:00:53,760 --> 00:00:56,640 Speaker 1: Forward Thinking Podcast all right, along with Joe McCormick. We 16 00:00:56,640 --> 00:01:00,160 Speaker 1: we did a really great introduction of what jeans are 17 00:01:00,200 --> 00:01:02,600 Speaker 1: and some of the really interesting cutting edge stuff going 18 00:01:02,600 --> 00:01:04,920 Speaker 1: on in gene therapy. So if you would like to 19 00:01:04,920 --> 00:01:07,119 Speaker 1: listen to that, we we highly recommend it. We think 20 00:01:07,120 --> 00:01:09,040 Speaker 1: that we did a pretty excellent job. Yeah. Yeah, the 21 00:01:09,080 --> 00:01:11,399 Speaker 1: fact we had Joe there too. You know, put facts 22 00:01:11,400 --> 00:01:13,400 Speaker 1: in between the jokes that I made and the shaking 23 00:01:13,440 --> 00:01:16,160 Speaker 1: of Lauren's head. It really was different from a tech 24 00:01:16,200 --> 00:01:19,200 Speaker 1: stuff episode. No, of course, I'm proud of all the 25 00:01:19,240 --> 00:01:21,320 Speaker 1: work we do, and then one was a great show. 26 00:01:21,600 --> 00:01:24,080 Speaker 1: But we're going to give an overview of what genes 27 00:01:24,080 --> 00:01:29,600 Speaker 1: are and some of the actual technical ways that scientists 28 00:01:29,640 --> 00:01:32,680 Speaker 1: and doctors are working with gene therapy right now, because 29 00:01:32,680 --> 00:01:35,680 Speaker 1: in the forward Thinking episode, it was more about the applications, 30 00:01:35,760 --> 00:01:37,520 Speaker 1: right it was more about why you would use it 31 00:01:37,760 --> 00:01:40,600 Speaker 1: and not how like how has it actually done? And 32 00:01:40,640 --> 00:01:44,160 Speaker 1: it's kind of fascinating. Yeah. Absolutely, and and this is, 33 00:01:44,200 --> 00:01:45,800 Speaker 1: by the way, one of those things that we kind 34 00:01:45,800 --> 00:01:47,480 Speaker 1: of struggle with all the time of of you know, 35 00:01:47,520 --> 00:01:49,280 Speaker 1: we'll we'll come up with a concept for a show 36 00:01:49,320 --> 00:01:51,720 Speaker 1: and then go, how should we check with car stuff? 37 00:01:51,760 --> 00:01:53,760 Speaker 1: Should we check with mind? Should we you know? Who 38 00:01:53,760 --> 00:01:55,520 Speaker 1: should we ask? And make sure that we're not treading 39 00:01:55,520 --> 00:01:58,240 Speaker 1: on their toes and re copying ourselves because we already 40 00:01:58,240 --> 00:02:01,880 Speaker 1: did a forward thinking episode and really the answer is always, um, 41 00:02:01,920 --> 00:02:05,080 Speaker 1: if it's interesting and there's more avenues within a topic 42 00:02:05,120 --> 00:02:07,360 Speaker 1: to talk about, then then we'll go ahead and cover it. 43 00:02:07,480 --> 00:02:11,600 Speaker 1: So let's start with the very basics. And but to 44 00:02:11,680 --> 00:02:13,639 Speaker 1: start with the very basics, we've got to look at 45 00:02:13,720 --> 00:02:18,680 Speaker 1: cellular biology. So anyone who was currently in middle school 46 00:02:19,040 --> 00:02:20,920 Speaker 1: is going to be able to go on about this 47 00:02:20,960 --> 00:02:23,799 Speaker 1: at length. I actually had to go back and look 48 00:02:23,880 --> 00:02:26,560 Speaker 1: up all this information because middle school was a long 49 00:02:26,600 --> 00:02:29,680 Speaker 1: time ago for me. And while I was originally interested 50 00:02:29,720 --> 00:02:34,120 Speaker 1: in going into biology, yeah I was, Biology was number one, 51 00:02:34,240 --> 00:02:37,240 Speaker 1: and then it's always terrible most mostly that was not 52 00:02:37,280 --> 00:02:40,120 Speaker 1: my branch of science anyway, Biology and physics I love them. 53 00:02:40,120 --> 00:02:41,880 Speaker 1: And then I got into college and I switched to 54 00:02:41,919 --> 00:02:44,760 Speaker 1: English literature with a focus on Shakespeare, and now I 55 00:02:44,760 --> 00:02:49,040 Speaker 1: talk about technology. So I mean it's a clear pathway. Yeah, 56 00:02:49,200 --> 00:02:54,840 Speaker 1: logical progression so sells, you know, sells the basic little 57 00:02:54,960 --> 00:02:58,480 Speaker 1: unit of life for for us, we human beings, and 58 00:02:58,560 --> 00:03:00,760 Speaker 1: most of the stuff we tend to interact with that 59 00:03:00,919 --> 00:03:05,160 Speaker 1: isn't super teeny tiny um cells have what is called 60 00:03:05,200 --> 00:03:08,400 Speaker 1: a nucleus. It's kind of the brain center of a cell, 61 00:03:08,480 --> 00:03:11,120 Speaker 1: the control center if you prefer, and they have a 62 00:03:11,160 --> 00:03:14,320 Speaker 1: cell membrane, and both of these things are incredibly important 63 00:03:14,360 --> 00:03:18,360 Speaker 1: with gene therapy. So within the nucleus you've got chromosomes, 64 00:03:18,360 --> 00:03:22,399 Speaker 1: and chromosomes are made up of two things, DNA and protein. 65 00:03:22,880 --> 00:03:25,919 Speaker 1: And the DNA is the that's sort of the very 66 00:03:25,960 --> 00:03:31,000 Speaker 1: basics of what makes you you. And along those chromosomes 67 00:03:31,000 --> 00:03:34,520 Speaker 1: are little sections of DNA that we call genes now. 68 00:03:34,560 --> 00:03:38,920 Speaker 1: The genes their job is to code for the production 69 00:03:39,120 --> 00:03:42,760 Speaker 1: of particular proteins, and that's what we call a gene 70 00:03:43,200 --> 00:03:47,000 Speaker 1: expressing itself. When a gene is expressed, it's coding for 71 00:03:47,120 --> 00:03:51,480 Speaker 1: a protein. And that's also important because with gene therapy, 72 00:03:51,640 --> 00:03:55,200 Speaker 1: one of the goals is to introduce new genes into 73 00:03:56,120 --> 00:04:00,040 Speaker 1: a cell so that a particular thing is express a 74 00:04:00,280 --> 00:04:04,520 Speaker 1: particular protein is created, and it doesn't always work right. 75 00:04:04,640 --> 00:04:08,280 Speaker 1: So and the reason for that is because gene therapy 76 00:04:08,320 --> 00:04:12,160 Speaker 1: this is still a very young science and uh and 77 00:04:12,520 --> 00:04:17,120 Speaker 1: sometimes the techniques we use have high success rates, sometimes 78 00:04:17,120 --> 00:04:19,800 Speaker 1: they have low success rates, and so it may be 79 00:04:19,920 --> 00:04:23,600 Speaker 1: that you're doing everything right but or as right as 80 00:04:23,640 --> 00:04:26,480 Speaker 1: we know how to do right now, but it's still 81 00:04:26,520 --> 00:04:30,800 Speaker 1: not you know, success rate right since it's so experimental. 82 00:04:30,920 --> 00:04:33,560 Speaker 1: Right now, we're currently on using gene therapy to um 83 00:04:33,640 --> 00:04:38,760 Speaker 1: to treat otherwise incurable diseases and particularly childhood diseases right 84 00:04:38,920 --> 00:04:42,479 Speaker 1: and only in clinical trials for that matter, right. You 85 00:04:42,480 --> 00:04:44,520 Speaker 1: you have to be part of a clinical trial, and 86 00:04:44,720 --> 00:04:46,839 Speaker 1: the only gene therapy that is going on is being 87 00:04:46,839 --> 00:04:49,920 Speaker 1: conducted on somatic cells. Those are those are body cells 88 00:04:49,960 --> 00:04:53,760 Speaker 1: as opposed to reproductive cells, right, which means that any 89 00:04:53,880 --> 00:04:56,800 Speaker 1: changes that are going on, and and the kinds of 90 00:04:56,880 --> 00:04:59,800 Speaker 1: changes that we're making are either inserting normal genes for 91 00:05:00,040 --> 00:05:03,840 Speaker 1: herring abnormal ones or altering the kind of on off 92 00:05:03,920 --> 00:05:07,200 Speaker 1: switches of those genes. Um they're only going to affect 93 00:05:07,200 --> 00:05:10,520 Speaker 1: the patient, and any hypothetical offspring of that patient would 94 00:05:10,520 --> 00:05:14,200 Speaker 1: not would not would not inherit those those genetic changes, 95 00:05:14,240 --> 00:05:18,240 Speaker 1: because again they're somatic, not the reproductive cells. So in 96 00:05:18,320 --> 00:05:21,320 Speaker 1: another issue would gene therapy. Similar to that is that 97 00:05:21,720 --> 00:05:26,040 Speaker 1: often the benefits that you experience with gene therapy are 98 00:05:26,080 --> 00:05:29,160 Speaker 1: temporary in nature, and that you have to undergo multiple 99 00:05:29,279 --> 00:05:34,200 Speaker 1: gene therapy sessions to have any lasting effect because they 100 00:05:34,279 --> 00:05:39,839 Speaker 1: don't necessarily uh change the genome. It doesn't necessarily change 101 00:05:39,880 --> 00:05:43,800 Speaker 1: everything like the actual uh way the cells are forming 102 00:05:43,839 --> 00:05:46,760 Speaker 1: from that point forward in your body. Right, It might 103 00:05:46,800 --> 00:05:51,080 Speaker 1: just affect the current expression of that current cell, that 104 00:05:51,120 --> 00:05:53,599 Speaker 1: current gene within that current cell, and if that cell dies, 105 00:05:53,960 --> 00:05:56,880 Speaker 1: then you know that's the the benefit you got from 106 00:05:56,880 --> 00:06:00,160 Speaker 1: that one cell is over. Yeah. I'll also, genes are 107 00:06:00,160 --> 00:06:04,080 Speaker 1: really complicated. They most of them make more than one protein. 108 00:06:04,120 --> 00:06:06,960 Speaker 1: That average is three, which is something that we've learned 109 00:06:06,960 --> 00:06:09,599 Speaker 1: from the Human Genome Project, which I'll be talking about 110 00:06:09,600 --> 00:06:12,880 Speaker 1: a little bit later on. It just means that, you know, 111 00:06:13,160 --> 00:06:16,880 Speaker 1: genes don't have they're not self contained bits of DNA, 112 00:06:17,040 --> 00:06:20,359 Speaker 1: and they don't have strictly defined roles. Yeah, so you 113 00:06:20,440 --> 00:06:23,400 Speaker 1: can't just say just get rid of that one, right, yeah, 114 00:06:23,400 --> 00:06:27,240 Speaker 1: because it could be that a disease is actually the problem. 115 00:06:27,320 --> 00:06:29,559 Speaker 1: You know, it might be the product of a few 116 00:06:30,000 --> 00:06:31,920 Speaker 1: different genes, and then you have to figure out, well, 117 00:06:31,920 --> 00:06:35,080 Speaker 1: which one of these genes is not behaving the right way, 118 00:06:35,440 --> 00:06:37,200 Speaker 1: you know, which one is the mutated gene, which one 119 00:06:37,200 --> 00:06:39,839 Speaker 1: do we need to replace? And then by replacing that 120 00:06:39,920 --> 00:06:42,520 Speaker 1: gene are we causing any other issues? Is there some 121 00:06:42,600 --> 00:06:45,719 Speaker 1: other problem that could happen as a result of going 122 00:06:45,760 --> 00:06:49,240 Speaker 1: in and altering a person's genes. And this is, like 123 00:06:49,279 --> 00:06:51,719 Speaker 1: I said, a very young science. So we're still learning, 124 00:06:51,760 --> 00:06:54,000 Speaker 1: and that's one of the reasons why clinical trials are 125 00:06:54,000 --> 00:06:56,560 Speaker 1: the only place, at least in the United States where 126 00:06:56,600 --> 00:07:00,120 Speaker 1: you can get gene therapy and you know, because honestly 127 00:07:00,240 --> 00:07:03,600 Speaker 1: it's not ready for a full rollout yet, certainly not now. 128 00:07:04,080 --> 00:07:07,719 Speaker 1: So here we've got a cell, we've got that cell membrane. 129 00:07:07,960 --> 00:07:11,520 Speaker 1: By the way, DNA does not pass through cell membranes. 130 00:07:11,560 --> 00:07:15,120 Speaker 1: Cell membranes are semipermeable, right, which means that they allow 131 00:07:15,360 --> 00:07:18,720 Speaker 1: some stuff through and they allow they keep other stuff 132 00:07:18,760 --> 00:07:23,400 Speaker 1: either inside or outside. Now, DNA generally speaking, is something 133 00:07:23,400 --> 00:07:26,440 Speaker 1: that cells want to keep inside. They don't like letting 134 00:07:26,480 --> 00:07:29,320 Speaker 1: the DNA go flying out all over the place. It's 135 00:07:29,320 --> 00:07:32,000 Speaker 1: a better idea, yes, So that means that if we 136 00:07:32,040 --> 00:07:34,720 Speaker 1: want to introduce DNA into a cell, we have to 137 00:07:34,800 --> 00:07:37,960 Speaker 1: kind of find a way of getting the DNA through 138 00:07:38,000 --> 00:07:42,040 Speaker 1: the membrane without damaging the cell because clearly or the DNA, 139 00:07:42,280 --> 00:07:44,600 Speaker 1: So if you kill the cell in the process, that 140 00:07:44,760 --> 00:07:46,720 Speaker 1: that's not what we call youthful. We call that. We 141 00:07:46,800 --> 00:07:50,560 Speaker 1: call that a fail that's that's generally speaking, that's a failure. 142 00:07:50,800 --> 00:07:53,280 Speaker 1: You don't you don't want the cell to die. So 143 00:07:53,760 --> 00:07:57,480 Speaker 1: finding a way to get DNA material into a cell, 144 00:07:57,920 --> 00:08:01,560 Speaker 1: So getting a good gene through that cell wall without 145 00:08:01,640 --> 00:08:04,880 Speaker 1: killing the cell has been really the main focus of 146 00:08:05,560 --> 00:08:09,880 Speaker 1: genetic therapy over the last couple of decades. So there 147 00:08:09,880 --> 00:08:11,600 Speaker 1: are a lot of different ways of doing it, and 148 00:08:11,640 --> 00:08:14,680 Speaker 1: we could either go about this chronologically or we could 149 00:08:15,280 --> 00:08:20,120 Speaker 1: try thematically or maybe alphabetically. But we kind of decided 150 00:08:20,200 --> 00:08:21,920 Speaker 1: like the first one we wanted to look at is 151 00:08:21,960 --> 00:08:26,320 Speaker 1: in a way, sort of the simplest, at least in concept, 152 00:08:26,440 --> 00:08:29,760 Speaker 1: if not in practice. And I guess the we're we're 153 00:08:29,760 --> 00:08:34,559 Speaker 1: going to cover two basic categories UM in this podcast 154 00:08:34,559 --> 00:08:37,120 Speaker 1: today and a couple of sort of outliers and and right, 155 00:08:37,160 --> 00:08:38,960 Speaker 1: there's a bunch more. We'll talk about that a little 156 00:08:38,960 --> 00:08:40,360 Speaker 1: bit at the tail end of the episode, and I 157 00:08:40,400 --> 00:08:44,520 Speaker 1: guess that we're sort of going chronologically a little bit. Yeah, 158 00:08:44,559 --> 00:08:47,080 Speaker 1: it's a it's a little bit of a jump around. 159 00:08:47,120 --> 00:08:49,600 Speaker 1: But but the first one we wanted to talk about 160 00:08:49,840 --> 00:08:54,000 Speaker 1: is micro injection, which is more or less what it 161 00:08:54,040 --> 00:08:57,640 Speaker 1: sounds like. Yeah, you're talking about a very very tiny 162 00:08:58,720 --> 00:09:02,760 Speaker 1: needle going into a cell and injecting DNA material directly 163 00:09:02,800 --> 00:09:06,840 Speaker 1: into either the cytoplasm, which is the the stuff inside 164 00:09:06,880 --> 00:09:10,520 Speaker 1: a cell membrane just in general. That's that's the uh, 165 00:09:10,640 --> 00:09:13,200 Speaker 1: both the fluid and all the little organelles and everything 166 00:09:13,200 --> 00:09:15,840 Speaker 1: that are in a cell, or you're injecting it directly 167 00:09:15,880 --> 00:09:18,160 Speaker 1: into the nucleus, which is where the d n A 168 00:09:18,280 --> 00:09:21,080 Speaker 1: material is kept. So in other words, you are using 169 00:09:21,280 --> 00:09:24,760 Speaker 1: a needle and you're just inserting the DNA directly there. Now, 170 00:09:25,080 --> 00:09:28,360 Speaker 1: when you're talking about cell cells are I don't know 171 00:09:28,360 --> 00:09:31,400 Speaker 1: if you know this, they're tiny. They're they're really little. Yeah, 172 00:09:31,480 --> 00:09:34,840 Speaker 1: you might think that, uh, the needle that you're getting 173 00:09:34,920 --> 00:09:38,200 Speaker 1: for techna shot is huge. Well it is pretty big, 174 00:09:38,240 --> 00:09:42,440 Speaker 1: but to a cell, that's gargantuan and I'm nearly positive 175 00:09:42,480 --> 00:09:45,840 Speaker 1: that many cells could fit inside. Yeah, so you need 176 00:09:45,880 --> 00:09:49,000 Speaker 1: to find a very very fine needle and you have 177 00:09:49,080 --> 00:09:51,280 Speaker 1: to be able to make. Really, you're not You're not 178 00:09:51,320 --> 00:09:54,560 Speaker 1: gonna You're not gonna just stumble over one of those. Okay, well, 179 00:09:54,600 --> 00:09:57,040 Speaker 1: I mean, you know, if you happen to stumble in 180 00:09:57,080 --> 00:10:01,600 Speaker 1: a lab, you might, but I accept that you make 181 00:10:02,000 --> 00:10:05,000 Speaker 1: an incredibly fine needle, and you actually you kind of 182 00:10:05,040 --> 00:10:07,160 Speaker 1: need to. One of them is just less fine than 183 00:10:07,200 --> 00:10:08,800 Speaker 1: the other one. The element is more of a pipette, 184 00:10:09,200 --> 00:10:11,400 Speaker 1: and the reason for that is you have to immobilize 185 00:10:11,480 --> 00:10:14,439 Speaker 1: the cell that you want to inject. You need to 186 00:10:14,480 --> 00:10:16,680 Speaker 1: kind of hold it down because otherwise cells are sort 187 00:10:16,679 --> 00:10:19,480 Speaker 1: of squid squiggly and yeah, they are. They do tend 188 00:10:19,480 --> 00:10:23,880 Speaker 1: to squiggle. Okay, So so this this technique was really pioneered. 189 00:10:24,240 --> 00:10:28,360 Speaker 1: The needle micro injection in general was pioneered by one 190 00:10:28,480 --> 00:10:31,839 Speaker 1: doctor Marshall Barber in the early nineteen hundreds. UM. He 191 00:10:31,920 --> 00:10:35,319 Speaker 1: was developing it to study bacteria and confirm the germ 192 00:10:35,440 --> 00:10:37,800 Speaker 1: theory that was being developed around that time by a 193 00:10:38,679 --> 00:10:45,599 Speaker 1: Cotchin pastor UM who would who would basically, um outline 194 00:10:45,640 --> 00:10:48,760 Speaker 1: the entire germs make a sick kind of contract, which 195 00:10:48,760 --> 00:10:51,520 Speaker 1: was revolutionary at the time. Right, it's still I'm still 196 00:10:51,559 --> 00:10:54,040 Speaker 1: pretty glad that we have it, and I think I 197 00:10:54,080 --> 00:10:57,800 Speaker 1: think it's great. So early on, like through the nineteen sixties, 198 00:10:57,880 --> 00:11:00,679 Speaker 1: early on, I mean, this was a very slowly developing 199 00:11:01,000 --> 00:11:04,839 Speaker 1: field of study. Uh. Microinjection was used to implant whole 200 00:11:04,960 --> 00:11:08,679 Speaker 1: organisms and embryos into larger bodies. Then in the nineteen 201 00:11:08,800 --> 00:11:13,520 Speaker 1: seventies we started implanting cellular organelles and molecules UM and 202 00:11:13,760 --> 00:11:17,160 Speaker 1: other relatively large bits of stuff into cells. And then 203 00:11:17,160 --> 00:11:19,840 Speaker 1: as we got into genetic study in the mid eighties, 204 00:11:19,880 --> 00:11:23,080 Speaker 1: we began injecting stuff like proteins and DNA and RNA 205 00:11:23,480 --> 00:11:27,240 Speaker 1: into cell nuclei. Right, So it obviously took quite a while. 206 00:11:27,400 --> 00:11:32,280 Speaker 1: And the general process, again at least conceptually, is simple. 207 00:11:32,400 --> 00:11:34,800 Speaker 1: You hold the cell still and then you inject the 208 00:11:34,800 --> 00:11:37,680 Speaker 1: stuff into it. Yep um, it's it's all. It's all 209 00:11:37,720 --> 00:11:41,160 Speaker 1: the same process, just just as a miniaturization of these 210 00:11:41,200 --> 00:11:46,480 Speaker 1: technologies began to get gooder. Yeah, right, because because otherwise 211 00:11:46,480 --> 00:11:49,320 Speaker 1: holding a cell still that's actually pretty tricky. They use 212 00:11:49,400 --> 00:11:51,840 Speaker 1: these pipettes that use a little bit of suction that 213 00:11:52,000 --> 00:11:55,600 Speaker 1: immobilize the cell, and then you have to have a 214 00:11:55,679 --> 00:11:58,960 Speaker 1: micro manipulator that's something that allows you to make very 215 00:11:59,120 --> 00:12:02,200 Speaker 1: very precise movements because you obviously you could not use 216 00:12:03,440 --> 00:12:06,960 Speaker 1: a handheld hypodermic needle. You wouldn't have the precision to 217 00:12:07,000 --> 00:12:10,920 Speaker 1: be able to to target specifically the nucleus with any 218 00:12:11,080 --> 00:12:13,240 Speaker 1: level of confidence. I was, I was pretty good at 219 00:12:13,280 --> 00:12:15,280 Speaker 1: duck Hunt, and I've got to say that I would 220 00:12:15,280 --> 00:12:18,000 Speaker 1: not that I don't have that kind of precision. The 221 00:12:18,040 --> 00:12:22,240 Speaker 1: hand eye coordination is pretty pretty uh remarkable. So yeah, 222 00:12:22,240 --> 00:12:24,440 Speaker 1: they usually you have some sort of device that is 223 00:12:24,520 --> 00:12:27,680 Speaker 1: designed to to study the needle and direct it properly. 224 00:12:28,480 --> 00:12:33,959 Speaker 1: So has limitations. There are some big ones actually. Also 225 00:12:34,000 --> 00:12:37,320 Speaker 1: in order to really use this technology, we we would 226 00:12:37,320 --> 00:12:39,559 Speaker 1: have to start getting into them what we learned through 227 00:12:39,559 --> 00:12:43,280 Speaker 1: the Human Genome Project, which um, which didn't really get 228 00:12:43,320 --> 00:12:47,160 Speaker 1: started until the nineteen nineties. I mean, it came about 229 00:12:47,200 --> 00:12:50,880 Speaker 1: after the Atomic Bomb Project in World War Two, actually 230 00:12:50,920 --> 00:12:55,280 Speaker 1: because Congress charged the Department of Energies predecessor agencies with 231 00:12:55,400 --> 00:12:59,960 Speaker 1: UM studying and analyzing genome structure, the replication, damage and repair, 232 00:13:00,000 --> 00:13:04,920 Speaker 1: air and and consequences of genetic mutations. UM. So you know, 233 00:13:05,080 --> 00:13:08,760 Speaker 1: especially those that were caused by radiation and the chemical 234 00:13:08,880 --> 00:13:14,800 Speaker 1: byproducts of warfare energy production. Right. So, UM, the Genome 235 00:13:14,800 --> 00:13:17,920 Speaker 1: Project completed its initial research a couple years ahead of 236 00:13:17,920 --> 00:13:23,240 Speaker 1: schedule in two thousand three. And UM, that's basically where 237 00:13:23,280 --> 00:13:26,120 Speaker 1: where we got most of our information. You know. That 238 00:13:26,120 --> 00:13:29,520 Speaker 1: that that that is the spawn, that the dawn of 239 00:13:30,480 --> 00:13:33,520 Speaker 1: gene knowledge, right, you know. Without that, obviously, we couldn't 240 00:13:33,559 --> 00:13:38,600 Speaker 1: make any um, any knowledgeable decision about how to go 241 00:13:38,679 --> 00:13:40,800 Speaker 1: about this at all. Right, we wouldn't know what was wrong, 242 00:13:40,920 --> 00:13:43,280 Speaker 1: much less how to correct it, all right. And so 243 00:13:43,320 --> 00:13:45,760 Speaker 1: that's that's why really everything that we're that we're talking 244 00:13:45,800 --> 00:13:48,080 Speaker 1: about has happened in the past like two decades. Yeah, 245 00:13:48,080 --> 00:13:51,800 Speaker 1: it's pretty exciting stuff. So this one does have micro injection, 246 00:13:51,840 --> 00:13:54,679 Speaker 1: does have some drawbacks. A big one is that you 247 00:13:54,720 --> 00:13:57,880 Speaker 1: can't really conduct this UH in vivo, meaning within the 248 00:13:57,920 --> 00:14:01,400 Speaker 1: body of a patient, because you can't you can't immobilize 249 00:14:01,440 --> 00:14:04,800 Speaker 1: the cells. You can't really use the micro manipulator to 250 00:14:04,880 --> 00:14:07,520 Speaker 1: inject something directly. All this kind of stuff tends to 251 00:14:07,520 --> 00:14:10,280 Speaker 1: be done in a laboratory, in a special lab dish 252 00:14:10,440 --> 00:14:14,560 Speaker 1: in the glass, right, Yep. You usually have a solution 253 00:14:14,679 --> 00:14:17,280 Speaker 1: and you end up using a little pipette to immobilize 254 00:14:17,320 --> 00:14:20,640 Speaker 1: the particular cell you want to UH to to manipulate. 255 00:14:20,720 --> 00:14:23,200 Speaker 1: And now a lot of times they would use bacteria 256 00:14:23,320 --> 00:14:25,280 Speaker 1: for this sort of thing, the idea being that the 257 00:14:25,280 --> 00:14:28,880 Speaker 1: bacteria would then transmit the DNA to other cells. But 258 00:14:28,920 --> 00:14:31,600 Speaker 1: we'll talk more about that and probably a future podcast. 259 00:14:31,680 --> 00:14:34,640 Speaker 1: It's it's really kind of immaterial to this UH. There 260 00:14:34,720 --> 00:14:36,520 Speaker 1: was another downside. It's that you have to do it 261 00:14:36,560 --> 00:14:40,440 Speaker 1: to one cell at a time, which is not terribly efficient. Nope. 262 00:14:40,720 --> 00:14:45,560 Speaker 1: And another UH drawback to this approach is that you 263 00:14:45,600 --> 00:14:48,160 Speaker 1: have to be really careful exactly where you inject that DNA. 264 00:14:48,520 --> 00:14:50,840 Speaker 1: They found out that if they injected the DNA into 265 00:14:50,840 --> 00:14:55,400 Speaker 1: the cytoplasm, it was far less effective than if they 266 00:14:55,480 --> 00:14:58,720 Speaker 1: injected it directly into the nucleus are possibly because the 267 00:14:59,040 --> 00:15:03,480 Speaker 1: electro light salute in the cytoplasm was degrading the DNA 268 00:15:03,560 --> 00:15:06,040 Speaker 1: before it could do anything useful. Right, So, you know, 269 00:15:06,200 --> 00:15:08,320 Speaker 1: just like we said earlier that just because you put 270 00:15:08,320 --> 00:15:11,320 Speaker 1: a new gene into a cell doesn't necessarily mean you're 271 00:15:11,320 --> 00:15:14,000 Speaker 1: going to see that gene express itself or be effective. 272 00:15:14,400 --> 00:15:16,440 Speaker 1: But they found that there was much more effective if 273 00:15:16,480 --> 00:15:19,560 Speaker 1: they did inject it directly into the nucleus. Uh So, 274 00:15:19,600 --> 00:15:22,760 Speaker 1: I mean it's it's certainly useful within the lab, but 275 00:15:23,040 --> 00:15:26,320 Speaker 1: within real world quote unquote settings where you're trying to 276 00:15:26,360 --> 00:15:29,800 Speaker 1: work on a patient directly, it's not. Now, if you 277 00:15:29,840 --> 00:15:34,240 Speaker 1: can develop an approach a cure like within the lab 278 00:15:34,360 --> 00:15:36,680 Speaker 1: within there and then implant those cells into the patient, 279 00:15:36,760 --> 00:15:39,720 Speaker 1: that might be a way to go. But in general, 280 00:15:39,840 --> 00:15:43,200 Speaker 1: this tends to be something we think about in terms 281 00:15:43,200 --> 00:15:45,960 Speaker 1: of learning more about what's working and what's not working, 282 00:15:46,000 --> 00:15:51,800 Speaker 1: as opposed to an approach um actual therapeutic treatment exactly. 283 00:15:52,160 --> 00:15:55,120 Speaker 1: So that kind of leads me to another one hydro 284 00:15:55,320 --> 00:15:58,680 Speaker 1: dynamic pressure, which again sounds you know, it's pretty much 285 00:15:58,720 --> 00:16:00,800 Speaker 1: what sounds like, I didn't read that much about this one. 286 00:16:01,000 --> 00:16:02,880 Speaker 1: Tell me, tell me what it is, all right. So 287 00:16:03,120 --> 00:16:06,840 Speaker 1: they found out that if you take a relatively large 288 00:16:06,880 --> 00:16:10,600 Speaker 1: amount of DNA material, and so for a human we're 289 00:16:10,600 --> 00:16:13,960 Speaker 1: talking about actually just a few millilets, but that's relatively 290 00:16:14,520 --> 00:16:18,800 Speaker 1: huge amounts of DNA, and then you take a needle 291 00:16:19,160 --> 00:16:21,840 Speaker 1: and you insert the needle into a blood vessel inside 292 00:16:21,840 --> 00:16:25,960 Speaker 1: that person, and then you inject that relatively large amount 293 00:16:25,960 --> 00:16:31,000 Speaker 1: of DNA very quickly into that blood vessel. Then this 294 00:16:31,480 --> 00:16:37,080 Speaker 1: the hydrodynamic pressure will cause cells along the blood vessels walls, 295 00:16:37,160 --> 00:16:41,760 Speaker 1: the indothelium, that's the layer that the lining. Uh, it'll 296 00:16:41,800 --> 00:16:45,480 Speaker 1: cause them to become more permeable, as well as the 297 00:16:45,680 --> 00:16:49,880 Speaker 1: perenchyma cells or paranchema cells. Now these are like tissue cells. 298 00:16:50,160 --> 00:16:51,960 Speaker 1: So this is like the cells of stuff that actually 299 00:16:52,000 --> 00:16:56,160 Speaker 1: does work depending upon whatever you know, Oregan, you are targeting. 300 00:16:56,520 --> 00:16:59,480 Speaker 1: So let's say it's the liver, all right. Well, they 301 00:16:59,520 --> 00:17:02,480 Speaker 1: found that also increases their permeability. So if you have 302 00:17:02,560 --> 00:17:05,280 Speaker 1: that DNA material and you inject it very quickly into 303 00:17:05,359 --> 00:17:08,719 Speaker 1: the blood vessel, then you can end up having a 304 00:17:08,760 --> 00:17:12,040 Speaker 1: lot more of that. Yeah, it ends up a lot 305 00:17:12,080 --> 00:17:15,520 Speaker 1: more cells are going to accept that DNA and potentially 306 00:17:15,840 --> 00:17:20,240 Speaker 1: you will start getting that gene expression, you're looking for. UM. 307 00:17:20,440 --> 00:17:23,239 Speaker 1: Couple of other downsides to this. Now they've they've been 308 00:17:23,359 --> 00:17:26,600 Speaker 1: using this with lab animals, not with people. All right, 309 00:17:26,680 --> 00:17:28,760 Speaker 1: so this is not something that's been tested on people, 310 00:17:28,840 --> 00:17:31,360 Speaker 1: but they've tested on mice and rats and it never 311 00:17:31,400 --> 00:17:34,400 Speaker 1: got to the human stage because well, because they found 312 00:17:34,440 --> 00:17:38,440 Speaker 1: out that sometimes this causes some cardial problems in the 313 00:17:38,520 --> 00:17:43,160 Speaker 1: car cardial and respiratory. Yeah. Yeah, So when they would 314 00:17:43,200 --> 00:17:48,280 Speaker 1: inject the vein along the tail of these critters, the 315 00:17:48,359 --> 00:17:50,439 Speaker 1: mice and the rats. They did it with a mouse, 316 00:17:51,119 --> 00:17:54,080 Speaker 1: the mouse would start to seem to have trouble breathing 317 00:17:54,200 --> 00:17:56,600 Speaker 1: for a couple of minutes and then recover and everything 318 00:17:56,600 --> 00:18:00,760 Speaker 1: seems to be okay. Rats could sometimes stop breathe entirely. 319 00:18:00,840 --> 00:18:04,239 Speaker 1: And they found that by massaging the abdomen's they could, uh, 320 00:18:05,119 --> 00:18:07,720 Speaker 1: they could they could end up getting the rats to 321 00:18:08,160 --> 00:18:11,040 Speaker 1: you know, kind of start breathing again. But they discovered 322 00:18:11,080 --> 00:18:14,280 Speaker 1: that using this approach put a lot of pressure on 323 00:18:14,359 --> 00:18:19,520 Speaker 1: the animals uh cardiovascular system, and that it would cause 324 00:18:20,040 --> 00:18:24,440 Speaker 1: everything from labored breathing to uh, irregular heartbeat. Uh. They 325 00:18:24,440 --> 00:18:28,439 Speaker 1: also discovered that the animals livers were expanding, sometimes up 326 00:18:28,440 --> 00:18:33,359 Speaker 1: to two of their original size. I guess that weirdly 327 00:18:33,840 --> 00:18:39,600 Speaker 1: makes sense. I mean, in terms of of liquid essentially, 328 00:18:39,640 --> 00:18:43,000 Speaker 1: you're essentially overloading the system, right, you know. And uh, 329 00:18:43,080 --> 00:18:47,920 Speaker 1: and so none of these um issues were permanent unless, 330 00:18:47,920 --> 00:18:50,680 Speaker 1: of course, the animal did not survive that initial reaction. 331 00:18:51,000 --> 00:18:55,399 Speaker 1: But the animals survived, then their various systems would return 332 00:18:55,400 --> 00:18:58,159 Speaker 1: to normal, Like they're breathing and heartbeat would return to 333 00:18:58,160 --> 00:19:00,920 Speaker 1: noble normal within a couple of minutes. Uh. Their liver 334 00:19:01,080 --> 00:19:04,000 Speaker 1: would go back to being normal sized within about half 335 00:19:04,000 --> 00:19:06,760 Speaker 1: an hour, and some of their other systems would take 336 00:19:07,040 --> 00:19:09,200 Speaker 1: up to two days or a day and a half 337 00:19:09,280 --> 00:19:12,800 Speaker 1: or so to get back to normal, but they started to. 338 00:19:12,960 --> 00:19:16,720 Speaker 1: They also would very frequently start expressing whatever the gene was, 339 00:19:16,800 --> 00:19:20,480 Speaker 1: so in front that side, it was a success. So 340 00:19:20,600 --> 00:19:23,399 Speaker 1: all of these so far have been interesting, UM, but 341 00:19:23,560 --> 00:19:27,880 Speaker 1: perhaps not the best way to actually treat human patients. UM. 342 00:19:27,920 --> 00:19:30,680 Speaker 1: We've got a couple more to talk about. But first, Yeah, 343 00:19:30,760 --> 00:19:34,959 Speaker 1: let's take a quick break to thank our sponsor. All right, 344 00:19:35,280 --> 00:19:37,639 Speaker 1: we're back. So we've talked a little bit about a 345 00:19:37,640 --> 00:19:41,280 Speaker 1: couple of different approaches that may we may never see 346 00:19:41,400 --> 00:19:44,239 Speaker 1: used as far as human applications go. I mean, there 347 00:19:44,240 --> 00:19:46,880 Speaker 1: are there's work in hydro dynamic to try and make 348 00:19:46,920 --> 00:19:49,920 Speaker 1: it a something that we could use with human patients. 349 00:19:50,000 --> 00:19:52,960 Speaker 1: But anything that would put that much stress on your 350 00:19:53,000 --> 00:19:56,240 Speaker 1: cardiovascular system for someone who's already trying to undergo medical 351 00:19:56,280 --> 00:19:59,119 Speaker 1: treatment is definitely not going to be the first choice, 352 00:19:59,240 --> 00:20:03,160 Speaker 1: right right, No, So let's talk about um, well, let's 353 00:20:03,160 --> 00:20:06,040 Speaker 1: talk about zapping cells. I was just thinking, you know, 354 00:20:06,080 --> 00:20:08,800 Speaker 1: if we can't if we can't really stab a needle 355 00:20:08,840 --> 00:20:11,800 Speaker 1: into a cell, if it's inside a person, and if 356 00:20:11,800 --> 00:20:15,240 Speaker 1: we can't really expect to jab a bunch of liquid 357 00:20:15,280 --> 00:20:17,480 Speaker 1: into a blood vessel and possibly cause a heart attack, 358 00:20:17,880 --> 00:20:21,840 Speaker 1: maybe we could just shock the heck out of them. Yeah, 359 00:20:21,840 --> 00:20:25,600 Speaker 1: that's clearly the next logical step. Um no, no, but 360 00:20:25,640 --> 00:20:28,040 Speaker 1: actually it does make a lot of sense. Yeah, because 361 00:20:28,080 --> 00:20:30,080 Speaker 1: I mean, we've got those membranes. They're not going to 362 00:20:30,240 --> 00:20:32,760 Speaker 1: let that DNA just go right on in. So how 363 00:20:32,760 --> 00:20:35,600 Speaker 1: do we convince it that we need to get this 364 00:20:35,720 --> 00:20:40,000 Speaker 1: DNA from outside the membrane inside the membrane? Right? Okay? 365 00:20:40,040 --> 00:20:43,320 Speaker 1: And one of one of the really cool and important 366 00:20:43,520 --> 00:20:45,600 Speaker 1: facts about cells that that you that you need to 367 00:20:45,600 --> 00:20:48,399 Speaker 1: realize here is it. Cell membranes are basically insulators that 368 00:20:48,440 --> 00:20:52,720 Speaker 1: are separating two charged regions, the the electrolyte or ionized 369 00:20:52,800 --> 00:20:56,359 Speaker 1: solution inside the cell and the electrolyte solution outside the cell. 370 00:20:56,760 --> 00:21:00,240 Speaker 1: So so they can they can act as capacitors. They 371 00:21:00,320 --> 00:21:03,159 Speaker 1: have they have capacitance. They do have capacitance, and if 372 00:21:03,200 --> 00:21:07,159 Speaker 1: you overload that capacitance, things go wonky. Stuff happens, right, So, 373 00:21:07,200 --> 00:21:10,600 Speaker 1: if you do it at the right amount of of charge, 374 00:21:10,960 --> 00:21:13,960 Speaker 1: then it ends up creating these pores, these these temporary 375 00:21:14,000 --> 00:21:16,520 Speaker 1: pores p o r e s. So you get these 376 00:21:16,520 --> 00:21:20,000 Speaker 1: little holes that form in the membrane, and it's temporary. 377 00:21:20,040 --> 00:21:24,080 Speaker 1: They will actually heal back up actually actually just a 378 00:21:24,080 --> 00:21:27,120 Speaker 1: few minutes. Yeah, within a few minutes after zapping them, 379 00:21:27,119 --> 00:21:29,520 Speaker 1: assuming that you're zapping them with the right amount of electricity, 380 00:21:29,520 --> 00:21:32,800 Speaker 1: because that's really important. So if you if you do 381 00:21:32,840 --> 00:21:36,280 Speaker 1: it at a low enough UH or well really it's 382 00:21:36,520 --> 00:21:43,080 Speaker 1: short high voltage zapps um very low amperage, and so 383 00:21:43,200 --> 00:21:46,600 Speaker 1: you're just doing these tiny little controlled zapps to the 384 00:21:46,600 --> 00:21:49,120 Speaker 1: the cell membrane, these holes will open up and then 385 00:21:49,119 --> 00:21:52,199 Speaker 1: within a few minutes after you've applied it, they'll close 386 00:21:52,240 --> 00:21:55,520 Speaker 1: back up again. So while they're open, then you can 387 00:21:55,560 --> 00:21:58,879 Speaker 1: coerce d NA to go in because DNA's are charged 388 00:21:58,960 --> 00:22:02,080 Speaker 1: particle and right so so especially since you've just changed 389 00:22:02,119 --> 00:22:05,480 Speaker 1: the capacitance of that membrane, it makes it easier for 390 00:22:05,560 --> 00:22:08,240 Speaker 1: stuff to slip through when it's also charged. So you 391 00:22:08,320 --> 00:22:10,679 Speaker 1: just you kind of you kind of corral it in 392 00:22:10,960 --> 00:22:13,600 Speaker 1: so you're you're you're driving the DNA and it's not 393 00:22:13,640 --> 00:22:16,520 Speaker 1: like it's just gonna you know, oh yeah, zip. You 394 00:22:16,520 --> 00:22:20,600 Speaker 1: actually have to guide it yourself, yourself being if you're 395 00:22:20,600 --> 00:22:22,719 Speaker 1: a scientist or doctor who's doing this sort of thing, 396 00:22:22,720 --> 00:22:26,200 Speaker 1: obviously probably not like no, no, no, no, probably would 397 00:22:26,200 --> 00:22:28,639 Speaker 1: not do this. I think Noel does want to stab 398 00:22:28,720 --> 00:22:33,720 Speaker 1: me with stuff, but probably not in a medicinal way. Anyway. 399 00:22:33,800 --> 00:22:38,240 Speaker 1: This is called electroporation. Obviously you're you've got the electro 400 00:22:38,359 --> 00:22:41,040 Speaker 1: and the pooration. You've got the making the poor. So 401 00:22:41,080 --> 00:22:43,040 Speaker 1: it all makes sense when you know what's going on. 402 00:22:43,720 --> 00:22:47,960 Speaker 1: This was originally investigated in the nineteen sixties, so doctors 403 00:22:48,000 --> 00:22:51,280 Speaker 1: began to experiment on cells within the lab that you know, 404 00:22:51,320 --> 00:22:54,800 Speaker 1: they're not looking at in vivo yet working in the lab, 405 00:22:54,800 --> 00:22:57,600 Speaker 1: and they were overloading the capacitance of the cellular membranes. 406 00:22:57,880 --> 00:23:01,000 Speaker 1: They were just introducing small amounts of electricity. Actually, originally, 407 00:23:01,040 --> 00:23:04,720 Speaker 1: what they were doing was They were using equipment called 408 00:23:04,800 --> 00:23:11,840 Speaker 1: electrophoresis apparatus. An electrophoresis is the manipulation of charged particles 409 00:23:11,880 --> 00:23:14,720 Speaker 1: through a solution. So if I have a solution that's 410 00:23:14,800 --> 00:23:17,919 Speaker 1: neutrally charged, and I put some charged particles in it, 411 00:23:18,040 --> 00:23:21,000 Speaker 1: like some negatively charged particles, let's say, and then I 412 00:23:21,080 --> 00:23:24,680 Speaker 1: generate a negative charge and move it close to those particles, 413 00:23:24,680 --> 00:23:27,560 Speaker 1: it's going to push them away, right, because like charges 414 00:23:27,600 --> 00:23:31,360 Speaker 1: repel one another. So you can actually move stuff through 415 00:23:31,400 --> 00:23:34,280 Speaker 1: a solution this way. And often in chemistry this is 416 00:23:34,359 --> 00:23:38,800 Speaker 1: used to separate materials out from a solution. And in 417 00:23:38,840 --> 00:23:42,760 Speaker 1: this case, it would be too convince d NA that 418 00:23:42,800 --> 00:23:45,000 Speaker 1: needs to go through that gigantic gaping hole in the 419 00:23:45,000 --> 00:23:47,960 Speaker 1: cell membrane right in front of it. And uh so 420 00:23:48,440 --> 00:23:50,520 Speaker 1: what they did was they took this equipment that was 421 00:23:50,560 --> 00:23:54,359 Speaker 1: meant to just guide charged particles, they short circuited it 422 00:23:54,480 --> 00:23:58,040 Speaker 1: on purpose and tried to use it to zappa cell wall. 423 00:23:58,359 --> 00:24:01,200 Speaker 1: So obviously, with this approach, it wasn't what you would 424 00:24:01,200 --> 00:24:05,400 Speaker 1: call precise. So but they they saw what the effect was, 425 00:24:05,560 --> 00:24:08,520 Speaker 1: but it wasn't fully controlled. Once once they got it 426 00:24:08,560 --> 00:24:11,520 Speaker 1: more under control, though, oh yeah, yeah, because they did 427 00:24:11,560 --> 00:24:13,560 Speaker 1: discover that it could affect the cell membrane. But they 428 00:24:13,600 --> 00:24:16,040 Speaker 1: also discovered that you could fry a cell. But if 429 00:24:16,040 --> 00:24:18,760 Speaker 1: you were able to get just the right amount of 430 00:24:18,800 --> 00:24:22,320 Speaker 1: electricity at the right frequency of pulses, you could cause 431 00:24:22,400 --> 00:24:26,119 Speaker 1: the cell membrane to create these pores and not harm 432 00:24:26,200 --> 00:24:30,120 Speaker 1: anything inside the cell itself, which of course is obviously important. 433 00:24:30,160 --> 00:24:32,000 Speaker 1: You don't want to kill the cell that you're trying 434 00:24:32,000 --> 00:24:34,760 Speaker 1: to introduce the new gene into. Right Again, that is 435 00:24:34,800 --> 00:24:37,679 Speaker 1: what we call a fail. Yeah, not not something you 436 00:24:37,720 --> 00:24:41,200 Speaker 1: want to have happen. So uh for a long time 437 00:24:41,520 --> 00:24:44,520 Speaker 1: they would work on this uh in vitro. So again 438 00:24:44,520 --> 00:24:47,520 Speaker 1: in the glass, they would have a glass of cells. 439 00:24:47,880 --> 00:24:52,480 Speaker 1: They would use a circuit that would encircle the solution 440 00:24:52,680 --> 00:24:56,080 Speaker 1: that the cells were inside. And this solution in this 441 00:24:56,119 --> 00:24:58,560 Speaker 1: case would be a conductive solution, meaning that it could 442 00:24:58,560 --> 00:25:02,000 Speaker 1: also conduct electricity. You turn on the electricity for the 443 00:25:02,080 --> 00:25:05,879 Speaker 1: right amount of time causes these pores to form, and 444 00:25:05,880 --> 00:25:08,240 Speaker 1: then you would corral the DNA into the pores, and 445 00:25:08,320 --> 00:25:10,760 Speaker 1: then you would check to see if the genes that 446 00:25:10,840 --> 00:25:13,639 Speaker 1: you wanted to have expressed in those cells were in 447 00:25:13,680 --> 00:25:18,200 Speaker 1: fact expressing themselves, either either making proteins or or etcetera. 448 00:25:18,359 --> 00:25:21,200 Speaker 1: If they weren't, you made them listen to Madonna over 449 00:25:21,240 --> 00:25:24,679 Speaker 1: and over until they got the message. I had to 450 00:25:24,720 --> 00:25:27,600 Speaker 1: make that joke somewhere, Lauren, it might as well be here. 451 00:25:29,600 --> 00:25:32,080 Speaker 1: You've got to make it fair enough, all right, So 452 00:25:32,160 --> 00:25:35,120 Speaker 1: we allow you the Madonna pun. Thank you. So this 453 00:25:35,200 --> 00:25:37,560 Speaker 1: was really promising, I mean, and in fact, it's promising 454 00:25:37,600 --> 00:25:43,800 Speaker 1: beyond gene therapy. That's just one application of this particular technique. Right, 455 00:25:43,880 --> 00:25:45,880 Speaker 1: These next couple of things that we're talking about UM 456 00:25:45,920 --> 00:25:52,600 Speaker 1: are also really effective for UM for introducing drugs into Yeah, 457 00:25:52,680 --> 00:25:56,080 Speaker 1: so let's say that you have a tumor and you 458 00:25:56,119 --> 00:25:59,280 Speaker 1: need to have some sort of chemotherapy delivered to it. Now, 459 00:25:59,680 --> 00:26:03,879 Speaker 1: tru sational chemotherapy is essentially affecting your entire body. You 460 00:26:03,880 --> 00:26:07,800 Speaker 1: you are poisoning yourself. You're doing in a very controlled way. 461 00:26:07,920 --> 00:26:10,480 Speaker 1: But yeah, and it's and and it and it can 462 00:26:10,520 --> 00:26:15,760 Speaker 1: be absolutely debilitating. Yeah, I've got friends who have gone 463 00:26:15,760 --> 00:26:17,960 Speaker 1: through it, and and it is it's hard to see. 464 00:26:18,320 --> 00:26:22,440 Speaker 1: So if you're able to to introduce that medicine directly 465 00:26:22,480 --> 00:26:25,120 Speaker 1: to the cells that you want to target, you can 466 00:26:25,119 --> 00:26:28,840 Speaker 1: target a very localized area. UM. And and since the nineties, 467 00:26:28,880 --> 00:26:31,360 Speaker 1: I think they have been researching how to do this 468 00:26:31,440 --> 00:26:34,520 Speaker 1: in in the body and yes, yeah, in vivo and uh. 469 00:26:34,600 --> 00:26:36,880 Speaker 1: And so that could mean that you have a very 470 00:26:37,040 --> 00:26:41,199 Speaker 1: much more effective treatment that has fewer side effects. It 471 00:26:41,320 --> 00:26:44,760 Speaker 1: doesn't eliminate the side effects, but it might make them 472 00:26:44,840 --> 00:26:49,400 Speaker 1: less traumatic for the patient. So the en vivo approach 473 00:26:49,880 --> 00:26:52,359 Speaker 1: is you might wonder, well, how could they use this 474 00:26:52,440 --> 00:26:59,960 Speaker 1: electrical uh technique within the body. And it's not entirely pleasant, folks. 475 00:27:01,440 --> 00:27:07,479 Speaker 1: They usually use either tiny electric plates or electrified hypodermic needles. 476 00:27:08,240 --> 00:27:10,280 Speaker 1: Oh man, you're saying all the words that I want 477 00:27:10,320 --> 00:27:15,119 Speaker 1: happening to my body better than cancer. Yes, So these 478 00:27:15,200 --> 00:27:18,399 Speaker 1: they would they would go to the location of wherever 479 00:27:18,440 --> 00:27:20,920 Speaker 1: it was they needed to introduce the genes. So let's 480 00:27:20,920 --> 00:27:24,320 Speaker 1: say it's your liver again, because that's it's a large oregon. 481 00:27:24,400 --> 00:27:26,480 Speaker 1: It's one that it's the one they think that they'll 482 00:27:26,520 --> 00:27:30,560 Speaker 1: have the most success on early because it's a large 483 00:27:30,960 --> 00:27:35,760 Speaker 1: oregon that's relatively easy to manipulate compared to some of 484 00:27:35,760 --> 00:27:39,960 Speaker 1: the others. So yeah, they would. They they would have 485 00:27:40,000 --> 00:27:44,800 Speaker 1: to either surgically insert these plates or they would have 486 00:27:44,920 --> 00:27:48,560 Speaker 1: to use these needles to introduce the electric current. Yeah, 487 00:27:48,720 --> 00:27:51,320 Speaker 1: and to to create the field exactly the way they 488 00:27:51,359 --> 00:27:56,359 Speaker 1: want to to introduce the DNA material into your system. Um, 489 00:27:56,359 --> 00:27:59,959 Speaker 1: it's pretty invasive, and that's one of the reasons why 490 00:28:00,359 --> 00:28:03,120 Speaker 1: there are some researchers who are trying to find some 491 00:28:03,200 --> 00:28:07,320 Speaker 1: other method to introduce gene therapy that's that wouldn't be 492 00:28:07,359 --> 00:28:09,919 Speaker 1: as invasive as this approach. All right, I think I 493 00:28:09,920 --> 00:28:12,439 Speaker 1: think didn't have a pretty bad reputation when it was 494 00:28:12,680 --> 00:28:14,960 Speaker 1: when it was still in the in vitros. Yeah, you know, 495 00:28:15,080 --> 00:28:19,960 Speaker 1: it wasn't. It wasn't great. Um, they were working with bacteria, 496 00:28:20,160 --> 00:28:25,760 Speaker 1: and they were killing bacteria cells pretty frequently, and they 497 00:28:25,760 --> 00:28:28,320 Speaker 1: really just needed one cell out of the batch to live. 498 00:28:28,400 --> 00:28:31,320 Speaker 1: So right, if you're like, if you're like, there's a 499 00:28:31,640 --> 00:28:33,760 Speaker 1: I gotta I got a couple of thousand cells in 500 00:28:33,800 --> 00:28:35,639 Speaker 1: this in this dish and only one of them has 501 00:28:35,680 --> 00:28:39,360 Speaker 1: to live, you don't necessarily go easy with the big 502 00:28:39,360 --> 00:28:42,560 Speaker 1: old switch, that says fry Um. And so it did 503 00:28:42,600 --> 00:28:45,760 Speaker 1: get a reputation for being a violent method of gene 504 00:28:45,800 --> 00:28:48,240 Speaker 1: therapy delivery. But then that's because they were working with 505 00:28:48,280 --> 00:28:52,000 Speaker 1: bacterial cells, not necessarily working with like and it wasn't 506 00:28:52,560 --> 00:28:55,120 Speaker 1: it wasn't in a patient. Yeah, if they could had 507 00:28:55,360 --> 00:28:57,360 Speaker 1: to be a little bit violent, right, but give it 508 00:28:57,400 --> 00:28:59,640 Speaker 1: a bad reputation. Yeah. So then you've got patients who 509 00:28:59,640 --> 00:29:02,719 Speaker 1: are like, I really don't want something where you're, you know, 510 00:29:03,080 --> 00:29:06,400 Speaker 1: essentially putting a cell sized electric chair into my body. 511 00:29:06,480 --> 00:29:09,600 Speaker 1: Please can we do something else? So yeah, there there's 512 00:29:09,600 --> 00:29:14,080 Speaker 1: another approach that essentially creates the same effect, but it 513 00:29:14,120 --> 00:29:17,600 Speaker 1: does it in a totally different mechanism. Right, sound operation, yes, 514 00:29:17,640 --> 00:29:20,720 Speaker 1: son operation so saw No, you start to think that 515 00:29:20,760 --> 00:29:22,400 Speaker 1: sounds like it might have something to do with sound, 516 00:29:22,440 --> 00:29:25,280 Speaker 1: and it does. It actually uses ultrasound. So you use 517 00:29:25,440 --> 00:29:29,040 Speaker 1: ultrasound at a particular frequency directed that the cells, and 518 00:29:29,480 --> 00:29:32,280 Speaker 1: the cells will end up forming these pores just as 519 00:29:32,320 --> 00:29:36,120 Speaker 1: they would with electroporation. Right, This was really pioneered in 520 00:29:36,120 --> 00:29:40,320 Speaker 1: in this first decade of the century. And uh, basically, 521 00:29:40,360 --> 00:29:42,080 Speaker 1: you put stuff that you want to get into a 522 00:29:42,120 --> 00:29:45,480 Speaker 1: cell into what's called a microbubble or a bunch of 523 00:29:45,520 --> 00:29:49,360 Speaker 1: microbubbles really, so exposing cell to to this ultrasound will 524 00:29:49,400 --> 00:29:53,240 Speaker 1: create the pores, changing the membranes conductivity and making it 525 00:29:53,280 --> 00:29:55,760 Speaker 1: easier for stuff to slip in. Right, and um, the 526 00:29:55,800 --> 00:29:59,560 Speaker 1: same ultrasound will also burst the microbubbles, which will release 527 00:29:59,680 --> 00:30:01,160 Speaker 1: the st up that you want to get into the 528 00:30:01,200 --> 00:30:03,680 Speaker 1: cell in a place that makes it easy to kind 529 00:30:03,680 --> 00:30:06,680 Speaker 1: of push in there. So interesting, So you have not 530 00:30:06,800 --> 00:30:08,920 Speaker 1: only not only is it opening up the doors, but 531 00:30:09,000 --> 00:30:12,480 Speaker 1: it unleashes the stuff that you want to deliver to 532 00:30:12,560 --> 00:30:15,120 Speaker 1: the cell itself, and you don't have to worry about 533 00:30:15,120 --> 00:30:17,840 Speaker 1: it being absorbed by the body some other way before 534 00:30:17,880 --> 00:30:20,560 Speaker 1: it can get to where it needs to go, right right. Um. 535 00:30:21,000 --> 00:30:24,400 Speaker 1: It can also burst the entire cell if you're not careful, 536 00:30:24,520 --> 00:30:27,680 Speaker 1: so that's the thing that you have to watch out for. Bummer. Yeah, 537 00:30:28,480 --> 00:30:31,560 Speaker 1: although from what I understand a lot of scientists refer 538 00:30:31,640 --> 00:30:34,640 Speaker 1: to this as being much less invasive than the electroporation 539 00:30:34,680 --> 00:30:37,480 Speaker 1: in vivo approach. Oh sure, sure, well, and any time 540 00:30:37,480 --> 00:30:39,640 Speaker 1: that you're talking about ultrasound, it's something that can be 541 00:30:39,680 --> 00:30:43,040 Speaker 1: applied um externally, Yeah, which is pretty cool. I mean 542 00:30:43,080 --> 00:30:47,240 Speaker 1: I've actually seen ultrasound also being suggested as a means 543 00:30:47,280 --> 00:30:51,520 Speaker 1: of directing nanoparticles to go straight to particular cells. So 544 00:30:51,600 --> 00:30:55,320 Speaker 1: it's like having a nano sized r C car moving 545 00:30:55,320 --> 00:30:59,800 Speaker 1: around the body. Doesn't work unless you're Martin Short and 546 00:30:59,840 --> 00:31:03,480 Speaker 1: you've got uh Quaid inside of you. Dennis Quaid is 547 00:31:03,520 --> 00:31:05,920 Speaker 1: inside of you, you know what I'm talking about. I 548 00:31:05,920 --> 00:31:09,160 Speaker 1: I know, I know inner Space, Yes, I'm familiar with it. 549 00:31:09,200 --> 00:31:13,480 Speaker 1: I'm I'm just thinking about the that that old Epcot 550 00:31:13,520 --> 00:31:16,479 Speaker 1: Red Body Wars. Yeah, that was in the old Wonders 551 00:31:16,480 --> 00:31:19,680 Speaker 1: of Life pavilion. That is sadly no more. I'm not sure. 552 00:31:19,800 --> 00:31:21,560 Speaker 1: I'm not sure if I'm sad about that. That was 553 00:31:21,640 --> 00:31:24,240 Speaker 1: not my favorite pavilion when I was a kids. Was great. 554 00:31:24,280 --> 00:31:28,160 Speaker 1: Cranium Command even better. Guys, all right, Disney fans out 555 00:31:28,160 --> 00:31:30,520 Speaker 1: there who know what I'm talking about with Cranium Command, 556 00:31:30,720 --> 00:31:33,320 Speaker 1: right in and tell me whether or not you loved 557 00:31:33,400 --> 00:31:36,200 Speaker 1: Cranium Command, because honestly, that is one of those attractions 558 00:31:36,240 --> 00:31:39,040 Speaker 1: I wish Disney would bring back. Also, if anyone here 559 00:31:39,080 --> 00:31:41,720 Speaker 1: happens to say work in the advertising department of Disney, 560 00:31:41,800 --> 00:31:44,720 Speaker 1: um call us because we we will clearly do Disney 561 00:31:44,760 --> 00:31:49,160 Speaker 1: as Yeah. So getting back into the actual gene therapy. 562 00:31:49,280 --> 00:31:51,560 Speaker 1: So there are other methods we could discuss. There are 563 00:31:51,560 --> 00:31:54,560 Speaker 1: a lot of things called viral vectors. And you might wonder, 564 00:31:54,680 --> 00:31:57,280 Speaker 1: why why would you ever use anything that has the 565 00:31:57,320 --> 00:31:59,440 Speaker 1: word viral in it. Well, well, there's there's a bunch 566 00:31:59,480 --> 00:32:02,240 Speaker 1: of different of different vectors that you can use. Um 567 00:32:02,320 --> 00:32:04,200 Speaker 1: and and and viruses are one of them. And this 568 00:32:04,280 --> 00:32:09,440 Speaker 1: is so fascinating to me because you're using really virulent 569 00:32:10,040 --> 00:32:13,280 Speaker 1: viruses and the kind of like like HIV or herpies 570 00:32:13,440 --> 00:32:16,680 Speaker 1: from in order to you kind of scrape out all 571 00:32:16,720 --> 00:32:21,560 Speaker 1: of the harmful DNA contained inside of a virus and 572 00:32:21,680 --> 00:32:24,440 Speaker 1: put in whatever you want to get into a cell, right, 573 00:32:24,480 --> 00:32:27,600 Speaker 1: and that sometimes can be RNA, can be DNA, or 574 00:32:27,640 --> 00:32:31,080 Speaker 1: it can even be a chemotherapy drug like we said before. 575 00:32:31,120 --> 00:32:33,720 Speaker 1: And the proteins on the outside of the virus, on 576 00:32:33,720 --> 00:32:36,400 Speaker 1: on the virus shell itself act as kind of like 577 00:32:36,440 --> 00:32:40,080 Speaker 1: a homing system, right. It will only end up interacting 578 00:32:40,160 --> 00:32:43,200 Speaker 1: with particular types of cells, because that's what viruses are. 579 00:32:43,720 --> 00:32:48,640 Speaker 1: They are they have this this uh, this the structure 580 00:32:48,880 --> 00:32:51,720 Speaker 1: that has them interact with very specific types of cells. 581 00:32:51,760 --> 00:32:54,400 Speaker 1: And they're very good at doing that. They're they're really 582 00:32:54,440 --> 00:32:56,920 Speaker 1: good at at invading a system, finding the kind of 583 00:32:56,920 --> 00:33:00,160 Speaker 1: cells that they that they want, and um and and 584 00:33:00,160 --> 00:33:02,800 Speaker 1: and stuff in there replicating like crazy. Yeah, So in 585 00:33:02,840 --> 00:33:05,280 Speaker 1: this case, instead of replicating, you would put in the 586 00:33:05,320 --> 00:33:09,840 Speaker 1: material that a virus need to deliver, either genes or 587 00:33:09,840 --> 00:33:12,440 Speaker 1: whatever you wanted. We'll talk more about that in the 588 00:33:12,440 --> 00:33:16,200 Speaker 1: future episode, because that's an entirely huge topic that we 589 00:33:16,200 --> 00:33:19,360 Speaker 1: could cover. Yeah. That and there's also um what's called 590 00:33:19,520 --> 00:33:24,920 Speaker 1: these biodegradable nanoparticles, which is a similar a similar vector 591 00:33:25,000 --> 00:33:30,240 Speaker 1: system in which you're directing um charged particles that are 592 00:33:30,280 --> 00:33:32,480 Speaker 1: going to go to a specific place and do a 593 00:33:32,520 --> 00:33:36,440 Speaker 1: specific thing. But um but instead of being kind of 594 00:33:36,480 --> 00:33:40,000 Speaker 1: piggybacking on a virus, you're you're doing it with with 595 00:33:40,080 --> 00:33:43,120 Speaker 1: nanoparticles that can be can be controlled through the properties 596 00:33:43,200 --> 00:33:46,040 Speaker 1: of those particles gotch. So it's so it's a synthetic 597 00:33:46,120 --> 00:33:49,720 Speaker 1: approach that kind of mimics what the virus does, but 598 00:33:49,800 --> 00:33:52,840 Speaker 1: allows us to have an external control system where we 599 00:33:52,880 --> 00:33:56,160 Speaker 1: say this particle we want to go here, and then 600 00:33:56,320 --> 00:33:58,200 Speaker 1: it can do what it needs to do. There are 601 00:33:58,200 --> 00:34:00,280 Speaker 1: other approaches that we could talk about and probably will 602 00:34:00,320 --> 00:34:05,040 Speaker 1: talk about in future episodes. For example, impale affection. Uh 603 00:34:05,200 --> 00:34:07,840 Speaker 1: does this have anything to do with staking vampires? It 604 00:34:07,960 --> 00:34:12,160 Speaker 1: does not. Uh, Buffy had nothing to do with this, No, 605 00:34:12,640 --> 00:34:14,719 Speaker 1: But it's pretty much what it sounds like. You know, 606 00:34:14,760 --> 00:34:17,920 Speaker 1: you're impaling stuff, and you've got the right material on 607 00:34:18,000 --> 00:34:21,120 Speaker 1: whatever it is you're impaling. So let's say that let's 608 00:34:21,120 --> 00:34:23,480 Speaker 1: say that you're you've got to sell that's the size 609 00:34:23,520 --> 00:34:27,200 Speaker 1: of I don't know, Spike and you've got you've got 610 00:34:27,239 --> 00:34:31,080 Speaker 1: a delivery system that's the size of Buffy and the 611 00:34:31,160 --> 00:34:36,080 Speaker 1: steak is covered in in uh in in strawberry jam, 612 00:34:36,280 --> 00:34:39,520 Speaker 1: and she steaks Spike and now he's got strawberry jam 613 00:34:39,520 --> 00:34:41,759 Speaker 1: in his system. That's essentially what this is. But we'll 614 00:34:41,760 --> 00:34:44,319 Speaker 1: go into more detail in the future episode, I promise. Um. 615 00:34:44,320 --> 00:34:48,359 Speaker 1: And there's also a laser beam gene transduction. We could 616 00:34:48,360 --> 00:34:50,600 Speaker 1: go into that, but that's another one of those that's 617 00:34:50,920 --> 00:34:53,960 Speaker 1: sort of on the developing side, and I thought that 618 00:34:53,960 --> 00:34:56,920 Speaker 1: that would really lend itself well to a second episode 619 00:34:56,920 --> 00:34:59,359 Speaker 1: if we decided to do that further down the line. Um, 620 00:34:59,480 --> 00:35:02,400 Speaker 1: we really going to concentrate on the these are these 621 00:35:02,480 --> 00:35:07,640 Speaker 1: physical exactly the ones where people are using technical tools 622 00:35:07,800 --> 00:35:12,439 Speaker 1: right now to experiment and see which delivery systems are 623 00:35:12,520 --> 00:35:15,360 Speaker 1: the most effective. Because again, just like just like I 624 00:35:15,360 --> 00:35:17,960 Speaker 1: said with the very first one and every single one 625 00:35:17,960 --> 00:35:21,840 Speaker 1: of these approaches, even being successful in introducing the DNA 626 00:35:21,920 --> 00:35:24,000 Speaker 1: to the cell, does not guarantee that you're going to 627 00:35:24,000 --> 00:35:26,920 Speaker 1: get the result you want. So it's one of those 628 00:35:26,920 --> 00:35:30,239 Speaker 1: things that we're still learning those basics. Yeah, and you know, 629 00:35:30,280 --> 00:35:33,000 Speaker 1: it's it's really it's really scary. Um, and a lot 630 00:35:33,040 --> 00:35:34,840 Speaker 1: of the things that I've that we've talked about, I 631 00:35:34,880 --> 00:35:37,960 Speaker 1: feel like we have ended on notes of of like 632 00:35:38,120 --> 00:35:41,880 Speaker 1: and that's terrifying because, um, but it's also incredibly promising, 633 00:35:41,920 --> 00:35:43,960 Speaker 1: you know, like I said at the beginning of the show, 634 00:35:44,040 --> 00:35:48,120 Speaker 1: especially for children that have incurable, terrible genetic diseases that 635 00:35:48,239 --> 00:35:52,400 Speaker 1: really have no other way of receiving therapy, this is this, 636 00:35:52,400 --> 00:35:54,839 Speaker 1: This is their best shot, and it's wonderful, right, Yes, 637 00:35:54,920 --> 00:35:58,000 Speaker 1: And while we're talking about just like you were saying, 638 00:35:58,080 --> 00:36:01,280 Speaker 1: like these high risk approaches, the risk is going down 639 00:36:01,800 --> 00:36:04,000 Speaker 1: over time because we learn more and we learn how 640 00:36:04,040 --> 00:36:07,520 Speaker 1: to how to apply it more effectively. So I personally 641 00:36:07,560 --> 00:36:11,360 Speaker 1: think this is a very promising area. And you know, 642 00:36:11,440 --> 00:36:14,320 Speaker 1: we didn't even touch on gene therapy to do stuff 643 00:36:14,360 --> 00:36:18,239 Speaker 1: like give you crazy awesome pecks or something, you know, 644 00:36:18,320 --> 00:36:20,960 Speaker 1: like yeah, none of the sci fi. Yeah, there's there's plenty. 645 00:36:21,200 --> 00:36:23,239 Speaker 1: We could do an entire episode about that too. About 646 00:36:23,280 --> 00:36:25,760 Speaker 1: all right, well, let's assume that we have perfected gene 647 00:36:25,800 --> 00:36:29,400 Speaker 1: therapy applications. Now we're able to go beyond just the 648 00:36:29,480 --> 00:36:32,840 Speaker 1: medical approach and we all either um, look like ethan 649 00:36:32,880 --> 00:36:35,880 Speaker 1: hawk or can shoot bees out of our hands. Yeah, 650 00:36:36,320 --> 00:36:40,600 Speaker 1: dogs with bark and bees come out. Um, fantastic. Well, 651 00:36:40,719 --> 00:36:44,719 Speaker 1: I look forward to our wicker Man future. Uh no, 652 00:36:45,080 --> 00:36:47,840 Speaker 1: this this really is an interesting topic. It was certainly 653 00:36:47,880 --> 00:36:51,239 Speaker 1: something that I I found fascinating as I researched more 654 00:36:51,239 --> 00:36:54,920 Speaker 1: and more about it. Because I had heard the terms. 655 00:36:54,960 --> 00:36:57,840 Speaker 1: I knew in general what was going on, but I 656 00:36:57,880 --> 00:37:00,960 Speaker 1: didn't know from a technical goal level or even a 657 00:37:01,080 --> 00:37:05,200 Speaker 1: cellular level, exactly what was happening. And it's pretty exciting stuff. 658 00:37:05,200 --> 00:37:08,200 Speaker 1: So I'm very interested to see how this field develops 659 00:37:08,239 --> 00:37:10,759 Speaker 1: over time. I'm hoping within our lifetime we start to 660 00:37:10,760 --> 00:37:15,200 Speaker 1: see some of these diseases just get eradicated through gene therapy. Alright, 661 00:37:15,239 --> 00:37:18,960 Speaker 1: so guys, if you have any suggestions for future episodes, 662 00:37:19,000 --> 00:37:21,200 Speaker 1: you've got some sort of topic you think we should cover, 663 00:37:21,600 --> 00:37:23,839 Speaker 1: and maybe your name is Mike and you know how 664 00:37:23,880 --> 00:37:25,920 Speaker 1: to use Twitter, you can get in touch with us 665 00:37:26,000 --> 00:37:28,960 Speaker 1: on Twitter, Facebook or even Tumbler. We are tech Stuff 666 00:37:29,080 --> 00:37:31,799 Speaker 1: hs W at all three of those locations. Or you 667 00:37:31,800 --> 00:37:34,400 Speaker 1: want to go old school and email us, Hey, you 668 00:37:34,440 --> 00:37:37,440 Speaker 1: can do that too. Our email address is tech stuff 669 00:37:37,560 --> 00:37:40,120 Speaker 1: at Discovery dot com and Lauren and I will talk 670 00:37:40,120 --> 00:37:46,880 Speaker 1: to you again really soon for more on this and 671 00:37:46,920 --> 00:37:49,440 Speaker 1: thousands of other topics because it has staff works dot 672 00:37:49,520 --> 00:37:55,280 Speaker 1: com