WEBVTT - There's a Gene for That 0:00:00.160 --> 0:00:07.400 Brought to you by Toyota. Let's go places. Welcome to 0:00:07.560 --> 0:00:14.480 Forward Thinking. Hey, they're welcome to Forward Thinking, the podcast 0:00:14.520 --> 0:00:16.840 that looks in the future and says, Billy Jean is 0:00:16.880 --> 0:00:21.040 not my lover. I'm Jonathan Strickland, I'm I'm Lauren foc 0:00:21.040 --> 0:00:25.000 obamb and I'm Joe McCormick. And that sound of disapproval 0:00:25.079 --> 0:00:27.640 is to the terrible quote that they chose to start 0:00:27.680 --> 0:00:33.080 this episode. We're talking about, right, Billy Jane. Yeah, uh 0:00:33.159 --> 0:00:35.600 so Jeane therapy. Billy Geane therapy is when you have 0:00:35.640 --> 0:00:38.040 to listen to to Michael Jackson songs until you feel better. 0:00:38.080 --> 0:00:40.120 But that's a good therapy, is a good therapy. I 0:00:40.320 --> 0:00:45.479 I don't mind that at all. It's it's the dancing here. Yeah. Now, 0:00:45.520 --> 0:00:49.960 gene therapy is something that has incredible potential but definitely 0:00:50.000 --> 0:00:53.199 had a rocky start. And uh, you know, if you 0:00:53.520 --> 0:00:56.680 don't really know that much about DNA and jeans or chromosomes, 0:00:56.680 --> 0:00:59.040 if all that confuses you, go back and listen. We 0:00:59.040 --> 0:01:01.840 we record a pocast immediately before this one should have 0:01:01.840 --> 0:01:05.400 published just before this podcast did that goes into sort 0:01:05.440 --> 0:01:08.800 of gene one oh one, and so listen to that one. 0:01:08.840 --> 0:01:11.600 So you can get caught up. We're gonna be pushing 0:01:11.600 --> 0:01:15.319 on right now talking about gene therapy, which is an 0:01:15.319 --> 0:01:19.760 attempt to treat genetic diseases at the molecular level. So 0:01:19.800 --> 0:01:24.479 you're actually trying to address molecules that have some form 0:01:24.600 --> 0:01:28.559 of defective element to them and replace those with quote 0:01:28.600 --> 0:01:33.080 unquote good molecules are good genes. So a good point 0:01:33.080 --> 0:01:35.600 of distinction maybe to start with, would be, um, how 0:01:35.680 --> 0:01:38.080 is this different than all of the normal ways we 0:01:38.120 --> 0:01:41.160 fight diseases? Well, a lot of the ways we fight diseases. 0:01:41.160 --> 0:01:43.479 There's of course ways where we just try and treat 0:01:43.520 --> 0:01:47.800 symptoms where we're not actually addressing the underlying problem, possibly 0:01:47.840 --> 0:01:50.440 because there may not be a way of addressing the 0:01:50.520 --> 0:01:53.080 underlying problem, or you're just letting your body do the 0:01:53.080 --> 0:01:55.960 work exactly maybe and you're just trying to make yourself 0:01:55.960 --> 0:01:58.000 feel better while that happened. For example, if you have 0:01:58.040 --> 0:02:01.360 a cold, there is no cure or for the common cold, right, 0:02:01.640 --> 0:02:04.200 but there are lots of different ways you can treat 0:02:04.240 --> 0:02:08.359 your symptoms and try to manage symptoms have different levels 0:02:08.360 --> 0:02:11.639 of efficacy depending upon whom you ask, but that's one 0:02:11.639 --> 0:02:13.320 way of doing it. Or for example, if you take 0:02:13.360 --> 0:02:16.720 an antibacterial medication to try to clear something out of 0:02:16.760 --> 0:02:19.760 your system that's attacking those bacteria that are attacking your 0:02:20.280 --> 0:02:22.360 your body in some way, shape or form. Right, So 0:02:22.400 --> 0:02:25.320 that's another way where you're actually trying to fight off 0:02:25.480 --> 0:02:30.080 some sort of quote unquote alien invasion. Alien in the 0:02:30.080 --> 0:02:33.359 sense of it doesn't belong inside of you. Uh. Your 0:02:33.400 --> 0:02:37.920 body uses antibodies, which are proteins that attack foreign cells 0:02:38.480 --> 0:02:41.320 or sometimes its own cells, depending on how your immune 0:02:41.320 --> 0:02:44.480 system is functioning. Right. Right, there are cases where you 0:02:44.520 --> 0:02:47.240 have things like allergic reactions where your body goes into 0:02:47.320 --> 0:02:50.480 overdrive trying to kill something that doesn't actually need to 0:02:50.480 --> 0:02:55.560 be killed. I speak from terrible, terrible experience. Uh. So 0:02:56.200 --> 0:02:58.880 these are all normal or quote unquote normal ways that 0:02:58.919 --> 0:03:04.799 we use to fight off illnesses. But some illnesses, genetic illnesses, 0:03:05.200 --> 0:03:08.520 have to do with actual information that's in our DNA, 0:03:09.040 --> 0:03:14.000 that is defective genes that are encoded the wrong way 0:03:14.320 --> 0:03:17.640 and therefore are not producing the proper proteins the right 0:03:17.680 --> 0:03:20.880 way for certain processes. And there's lots of different types 0:03:20.880 --> 0:03:25.200 of genetic diseases that cover a wide range. So we're 0:03:25.240 --> 0:03:26.880 not gonna go and talk about all of them, because 0:03:26.919 --> 0:03:30.040 that's that alone would be a series of podcasts. But 0:03:30.560 --> 0:03:35.600 one common element here is that these diseases have these 0:03:35.640 --> 0:03:38.320 these faulty genes at the very core of the problem. 0:03:38.400 --> 0:03:42.240 And if we were somehow able to remove the faulty 0:03:42.320 --> 0:03:47.120 genes from ourselves and insert good, healthy genes in their place, 0:03:47.760 --> 0:03:52.720 we could end up possibly curing the disease. Or if 0:03:52.760 --> 0:03:55.400 we could figure out how to um turn on or 0:03:55.440 --> 0:03:58.800 off a gene that is doing the opposite thing right, 0:03:58.960 --> 0:04:01.360 right and keeping my jeans. You know, we didn't talk 0:04:01.400 --> 0:04:04.480 about this in the last podcast, but it does bear saying. 0:04:04.480 --> 0:04:07.600 And I think jeans are complicated, right, So you know 0:04:07.960 --> 0:04:10.440 you didn't say that, well, well in the s in 0:04:10.480 --> 0:04:12.400 the sense of like, if you think, think of Jeanes 0:04:12.480 --> 0:04:15.360 like a switchboard. Alright, So think about a switchboard where 0:04:15.360 --> 0:04:18.680 every single switch is connected to a an LED light. 0:04:18.760 --> 0:04:21.719 So you've got a bank of LED lights, and you've 0:04:21.720 --> 0:04:23.600 got a bank of switches, and when you turn on 0:04:24.000 --> 0:04:26.560 a switch an L a ED light comes on, and 0:04:26.600 --> 0:04:28.600 then when you turn it off, the LED light goes off. 0:04:28.920 --> 0:04:31.680 If that's all jeanes were, we'd be set. That would 0:04:31.680 --> 0:04:34.440 be so easy to fix. But what actually happens is 0:04:34.480 --> 0:04:38.359 you have to flip like seven random switches all across 0:04:38.400 --> 0:04:40.320 the board to make the light come on, right, and 0:04:40.360 --> 0:04:42.680 if you also turns a few other lights on, and 0:04:42.680 --> 0:04:46.080 it also makes a weird quacking noise. Right, we're back 0:04:46.080 --> 0:04:48.280 to the potypus. If you and if you turn, if 0:04:48.320 --> 0:04:50.920 you turn one switch off, maybe the quacking noise goes 0:04:50.960 --> 0:04:53.000 off and three of the lights go off, but then 0:04:53.120 --> 0:04:56.120 five more lights come on. It's so complex and it's 0:04:56.200 --> 0:04:59.800 only and it's within this this uh network of g 0:05:00.000 --> 0:05:02.720 means and how they all express themselves. Keeping in mind 0:05:02.720 --> 0:05:06.640 that some genes can express themselves in multiple ways. That's 0:05:06.680 --> 0:05:09.600 why it's it's not so easy as just say, you know, 0:05:09.960 --> 0:05:13.719 turn that one switched the button. Yeah, the word for 0:05:13.839 --> 0:05:17.120 what all of the genes produced together is the phenotype. 0:05:17.560 --> 0:05:20.000 That's sort of the external expression of when you've got 0:05:20.040 --> 0:05:23.599 all the switches switched on. And so the goal of 0:05:23.680 --> 0:05:27.680 gene therapy is to address these faulty genes and to 0:05:27.800 --> 0:05:29.800 fix them in a way that is not harmful to 0:05:29.800 --> 0:05:33.599 the patient, which can also be very difficult because again 0:05:33.640 --> 0:05:37.080 it's really complex. Sometimes when you're when you think you're 0:05:37.120 --> 0:05:39.520 fixing one thing, you might be actually creating a much 0:05:39.600 --> 0:05:42.480 larger problem or maybe just a different problem. And I've 0:05:42.480 --> 0:05:45.200 got some really interesting examples that are terrifying about that. 0:05:45.240 --> 0:05:48.120 You can't wait to get to that. So let's talk 0:05:48.160 --> 0:05:51.920 a little bit about mutations. You know, how how do 0:05:52.040 --> 0:05:54.760 genes mutate in the first place? Uh? And there's actually 0:05:54.839 --> 0:05:56.840 quite a few ways. First of all, when you're talking 0:05:56.880 --> 0:06:00.440 about genes, you're talking about this this data essentially that's 0:06:00.600 --> 0:06:04.920 encoded in DNA, and that data gets copied over and 0:06:04.960 --> 0:06:07.760 over and over again during cellular division. You get copies 0:06:07.760 --> 0:06:12.159 of your d N a uh, and sometimes changes happen 0:06:12.240 --> 0:06:16.679 when these copies. Sometimes sometimes mistakes are made, so to speak. 0:06:16.680 --> 0:06:18.160 So it's kind of like, you know, if you were 0:06:18.200 --> 0:06:20.280 to ever make a copy of a copy of a 0:06:20.320 --> 0:06:22.320 copy of a copy on a photocopy, or you know 0:06:22.360 --> 0:06:25.640 that final copy doesn't look as good as that original one. 0:06:26.320 --> 0:06:28.880 In a very basic way, that's kind of similar to 0:06:28.960 --> 0:06:32.680 what I'm talking about here. Also, environmental factors can cause 0:06:32.880 --> 0:06:38.600 changes to your genes, so right, or even you know 0:06:38.880 --> 0:06:40.919 what what chemicals are in the food you eat, the 0:06:40.920 --> 0:06:43.119 water you drink, or the other stuff that you drink, 0:06:43.600 --> 0:06:45.919 you know, all sorts of stuff. I think things like 0:06:46.000 --> 0:06:50.520 stress can affect your genes to some extent. So you know, 0:06:50.880 --> 0:06:53.080 there are a lot of different factors here. It's very, 0:06:53.240 --> 0:06:55.680 very complex, and most of those changes that are going 0:06:55.720 --> 0:06:58.080 to happen are going to happen in um somatic cells, 0:06:58.240 --> 0:07:01.480 in your bodily cells, not in your um sex chromosome 0:07:01.560 --> 0:07:04.400 cells that are are passed on too, or your chromosomes 0:07:04.400 --> 0:07:07.080 period that are passed on to your children. UM, that's 0:07:07.120 --> 0:07:10.320 that's a epo genetics, and that's a whole different, whole 0:07:10.360 --> 0:07:13.240 different issue. But but some of the changes can lead 0:07:13.280 --> 0:07:15.520 to like we talked about in our stress, some of 0:07:15.520 --> 0:07:18.240 them can can potentially be inherited. Whether or not that 0:07:18.320 --> 0:07:21.960 ends up expressing itself in offspring is another question. So 0:07:22.040 --> 0:07:25.200 one interesting thing I think about inherited genetic diseases is 0:07:25.240 --> 0:07:29.360 that for the most part, they're recessive. So in order 0:07:29.440 --> 0:07:33.320 for you to have a full expression of a genetic disease, 0:07:33.720 --> 0:07:37.000 you have to have inherited two copies of the mutated 0:07:37.040 --> 0:07:39.920 gene to really inherit the disorder. When you think about this, 0:07:39.960 --> 0:07:43.480 isn't that surprising, right? You wouldn't You wouldn't expect for 0:07:43.640 --> 0:07:47.480 most genetic diseases to be in dominant genes because uh 0:07:47.520 --> 0:07:51.360 in in any species, because if it were a dominant expression, 0:07:51.600 --> 0:07:56.360 then those those life forms, whatever creature you're talking about, 0:07:56.920 --> 0:07:58.920 most of them probably wouldn't get to an age where 0:07:58.920 --> 0:08:02.360 they could reproduce, and that gene would eventually phase its 0:08:02.360 --> 0:08:05.480 way out of the overall population. But if it's a 0:08:05.520 --> 0:08:12.040 recessive gene, then not that many comparatively speaking, will display 0:08:12.080 --> 0:08:15.400 this or will express this gene, this trait of this, uh, 0:08:15.480 --> 0:08:19.480 this whatever the genetic diseases um. So it can actually 0:08:19.560 --> 0:08:22.280 continue to exist within a population longer than it would 0:08:22.280 --> 0:08:25.440 if it were a dominant gene. So that I thought 0:08:25.480 --> 0:08:28.480 was really interesting. But let's let's talk about kind of 0:08:28.480 --> 0:08:32.960 the history of gene therapy itself, so we kind of 0:08:33.000 --> 0:08:35.720 find why it could be potentially really helpful in the 0:08:35.760 --> 0:08:39.760 fields of medicine. It was back in nineteen seventy two 0:08:40.520 --> 0:08:42.560 when there was a paper that was authored by a 0:08:42.640 --> 0:08:46.080 parent Friedman and Roblin who the pair wrote a paper 0:08:46.120 --> 0:08:51.760 called gene Therapy for Human Genetic Disease question mark because 0:08:51.760 --> 0:08:54.800 they were actually asking the question could gene therapy potentially 0:08:54.960 --> 0:08:59.520 address this? And they proposed replacing defective DNA with good 0:09:00.040 --> 0:09:03.319 un quote DNA uh. They also cited the first attempts 0:09:03.360 --> 0:09:06.160 at gene therapy experiments going back all the way to 0:09:06.240 --> 0:09:09.679 nineteen seventy. Now, this paper was written in seventy two, UH, 0:09:09.720 --> 0:09:12.400 and in fact, other sources I saw said that the 0:09:12.440 --> 0:09:14.920 experiments that happened in the seventies and eighties were in 0:09:15.040 --> 0:09:20.920 large part unauthorized trials, which that leads to some pretty 0:09:21.000 --> 0:09:24.520 serious setbacks in gene therapy. As when I get up 0:09:24.520 --> 0:09:27.320 into the nineties, I'll talk more about that, UM, but 0:09:27.600 --> 0:09:30.920 gene therapy isn't as far along as it potentially could be. 0:09:31.520 --> 0:09:36.320 I think in part because of some overenthusiastic but perhaps 0:09:36.440 --> 0:09:42.199 misguided trials, and so in labs that were in the 0:09:42.280 --> 0:09:45.319 National Heart, Lung, and Blood Institute and in the National 0:09:45.400 --> 0:09:50.040 Cancer Institute conducted experiments which showed cells from a patient 0:09:50.120 --> 0:09:53.240 with a d A deficiency UH that's out of no 0:09:53.440 --> 0:09:57.080 scene d M in as deficiency, which affects the immune 0:09:57.080 --> 0:10:01.000 systems ability to fight off infection. Those could be corrected 0:10:01.080 --> 0:10:05.559 in a tissue culture using a retrovirus to insert corrected 0:10:05.600 --> 0:10:08.880 genes into the cells. And this is actually still how 0:10:08.880 --> 0:10:12.960 they're mostly proposing to do gene therapy. Right. Virus it's 0:10:13.040 --> 0:10:16.960 one of the ways. UH. Viruses have some issues, but 0:10:17.040 --> 0:10:19.880 viruses are really good at penetrating cells. I mean, that's 0:10:19.920 --> 0:10:22.400 what they do in order to replicate, right, And we've 0:10:22.400 --> 0:10:25.840 said before that sometimes it makes more sense not to 0:10:25.960 --> 0:10:29.480 try and copy or outdo mother nature, but to just 0:10:30.120 --> 0:10:33.079 use it, Yeah, coopt what mother nature is already doing. Right. 0:10:33.400 --> 0:10:35.439 If you take a virus and you strip out all 0:10:35.440 --> 0:10:37.880 the stuff that makes it dangerous, essentially it's ability to 0:10:37.920 --> 0:10:41.920 self replicate and any other uh, information that would otherwise 0:10:41.960 --> 0:10:44.760 alter your cells, and then put in the stuff you 0:10:44.800 --> 0:10:48.760 want to have injected into a cell, and then introduce 0:10:48.840 --> 0:10:53.320 that into the tissue or patient. Then it does the 0:10:53.320 --> 0:10:56.000 work for you. I mean, it's a perfect machine of viruses. 0:10:56.320 --> 0:10:59.680 Is a machine designed to inject DNA into foreign cells. 0:10:59.760 --> 0:11:02.240 Right now, there are some problems, uh. First of all, 0:11:02.280 --> 0:11:05.240 I mean there's everyone's always worried about the idea of 0:11:05.360 --> 0:11:07.760 using viruses in the first place, especially they don't understand 0:11:07.800 --> 0:11:10.319 a lot about how viruses work. But it's also not 0:11:10.960 --> 0:11:13.640 ideal for every situation. For example, if you want to 0:11:13.679 --> 0:11:17.360 treat something that is found in brain tissue, virus is 0:11:17.360 --> 0:11:20.280 a bad idea because viruses are too large to penetrate 0:11:20.320 --> 0:11:23.000 the blood brain barrier. So you've got to find something 0:11:23.040 --> 0:11:25.480 that's even smaller than a virus, your typical virus to 0:11:25.480 --> 0:11:28.720 be able to penetrate that barrier to deliver the good 0:11:28.880 --> 0:11:34.160 DNA to brain tissue. They are developing um I think 0:11:34.200 --> 0:11:37.640 that they are currently developing some methods specifically with Parkinson's 0:11:37.679 --> 0:11:42.680 disease that that may use viruses. But there there's the 0:11:42.720 --> 0:11:48.160 main approach I've seen is using liposomes and creating essentially 0:11:48.600 --> 0:11:52.240 a plastic coding for liposomes that would allow it to 0:11:52.360 --> 0:11:56.160 move through the blood brain barrier effortlessly compared to most 0:11:56.200 --> 0:11:58.360 viruses which would not be able to penetrate it. They 0:11:58.400 --> 0:12:00.679 are also playing with different kinds of virus is these days. 0:12:00.720 --> 0:12:03.680 I think originally retroviruses were what we're being used in 0:12:03.800 --> 0:12:07.760 these days, um lent of viruses are being used things 0:12:07.800 --> 0:12:11.480 like um HIV actually that have a really long incubation 0:12:11.559 --> 0:12:16.440 period and can infect non dividing cells. So it interesting 0:12:16.520 --> 0:12:19.079 winds up doing. But continue, continue with your time, back 0:12:19.120 --> 0:12:22.160 to the history. So we've we've got this this retrovirus 0:12:22.200 --> 0:12:25.160 that was used in this early experiment, they showed that 0:12:25.400 --> 0:12:29.800 it could be done. In six they began to experiment 0:12:29.840 --> 0:12:33.840 to introduce correct genes into bone marrow cells and animals 0:12:34.080 --> 0:12:36.000 to see how safe it would be as a treatment. 0:12:36.040 --> 0:12:38.160 So they're using the animal's actual bone marrow cells to 0:12:38.200 --> 0:12:42.160 deliver good quote unquote DNA and the conclusion was that 0:12:42.200 --> 0:12:45.800 it was safe, but they didn't get the correct gene 0:12:45.880 --> 0:12:49.080 to enough cells for it to be considered effective. So, 0:12:49.120 --> 0:12:51.800 in other words, bone marrow just wasn't the right vector 0:12:52.040 --> 0:12:56.360 for delivering this kind of treatment. It worked, but non 0:12:56.400 --> 0:12:58.920 a level that would have created enough change for it 0:12:58.960 --> 0:13:03.080 to be a good treat it. So in they try 0:13:03.520 --> 0:13:06.960 white blood cells instead of bone marrow cells, and that 0:13:07.080 --> 0:13:10.360 increased the number of cells that were affected. So they thought, 0:13:10.360 --> 0:13:14.000 ha ha, here we're onto something. Uh. And in there 0:13:14.040 --> 0:13:17.560 was an experiment with tumor infiltrating lympho sites t i 0:13:17.800 --> 0:13:21.240 L cells UH that showed that using a virus to 0:13:21.320 --> 0:13:24.240 insert DNA material would be a safe form of treatment. Now, 0:13:24.320 --> 0:13:28.160 this experiment was more about inserting a DNA marker into 0:13:28.200 --> 0:13:31.520 t I L cells. It wasn't about putting in good DNA. 0:13:31.679 --> 0:13:34.680 It was about identifying this cell as a t I 0:13:34.920 --> 0:13:38.080 L cell. But the one of the other pieces of 0:13:38.120 --> 0:13:40.160 information they got was, oh, well, this could work for 0:13:40.200 --> 0:13:43.040 other applications beyond just marking a cell. We might be 0:13:43.080 --> 0:13:47.880 able to actually do gene therapy using this approach. Sotumber four, 0:13:49.480 --> 0:13:52.320 the National Institutes of Health treated a four year old 0:13:52.320 --> 0:13:55.959 girl with a d A deficiency. They also treated nine 0:13:56.000 --> 0:13:58.520 year old girl with a d A deficiency, and this 0:13:58.559 --> 0:14:02.800 was one of the first approved of trials for g therapy. 0:14:02.880 --> 0:14:08.720 So this approach was not incredibly effective at first, although 0:14:09.280 --> 0:14:12.480 the last information I could find both patients are leading 0:14:13.120 --> 0:14:16.160 normal lives now they do not have this a d 0:14:16.280 --> 0:14:22.440 A deficiency apparently anymore. But the the delivery methods have 0:14:22.560 --> 0:14:27.800 improved significantly since nine. There was actually very few successes 0:14:28.320 --> 0:14:32.120 in early gene therapy experiments all the way through the 0:14:32.160 --> 0:14:35.120 eighties into the nineties, and that was one of the 0:14:35.200 --> 0:14:40.640 reasons why gene therapy took had a real rough go 0:14:40.840 --> 0:14:43.400 in the early days. Right, not a big surprise. We're 0:14:43.400 --> 0:14:47.520 talking about something incredibly sophisticated that we have admittedly only 0:14:47.720 --> 0:14:51.200 a you know, a sliver of understanding, Like there's so 0:14:51.320 --> 0:14:54.760 much we don't know about genes, right, and we hadn't 0:14:54.760 --> 0:14:58.240 mapped the human genome until right, So it's it's not 0:14:58.320 --> 0:15:01.640 a big surprise that it took a while because we 0:15:01.640 --> 0:15:03.800 were still learning about what we were doing while we 0:15:03.800 --> 0:15:09.640 were doing it. Um Dr Claudio Born and none of 0:15:09.680 --> 0:15:14.320 the Vita Salute. San Rafael University in Milan experimented with 0:15:14.400 --> 0:15:19.120 gene therapy delivery systems using a hematopoetic stem cells to 0:15:19.240 --> 0:15:22.920 deliver genes. So now we're trying other methods of stem 0:15:22.960 --> 0:15:28.480 cells was another vector in researchers used gene therapy to 0:15:28.520 --> 0:15:32.240 treat babies who had a d A deficiency and moving 0:15:32.280 --> 0:15:36.000 up to nine. This was this was a terrible year 0:15:36.360 --> 0:15:39.280 for gene therapy. It was a terrible tragedy as well. 0:15:39.840 --> 0:15:42.120 So there have been very there's been a lot of trials, 0:15:42.680 --> 0:15:47.800 very few successes, but the entire discipline of gene therapy 0:15:47.880 --> 0:15:51.480 suffered a serious setback because Uh, there was a patient 0:15:51.520 --> 0:15:54.240 who was undergoing gene therapy to treat a liver disease 0:15:54.560 --> 0:15:58.240 at the University of Pennsylvania. That patient's name is Jesse Gelsinger. 0:15:58.920 --> 0:16:03.680 Jesse Gelsinger uh died during the trial and it was 0:16:03.720 --> 0:16:07.400 the first death attributable to gene therapy. That led to 0:16:07.520 --> 0:16:11.760 increased scrutiny of gene therapy programs across the entire world, 0:16:12.280 --> 0:16:14.960 and a lot of conclusions were drawn that many, not 0:16:14.960 --> 0:16:18.720 not all, but many of these trials did not follow 0:16:18.920 --> 0:16:22.120 terribly rigorous standards, or perhaps were not designed in the 0:16:22.120 --> 0:16:25.880 most ethical manner. The the desire to try and be 0:16:25.960 --> 0:16:30.120 the first to UH to have a working gene therapy 0:16:30.480 --> 0:16:35.400 might have been guiding people to act recklessly, particularly with 0:16:35.440 --> 0:16:38.800 the lives or well being of patients. And it raised 0:16:38.840 --> 0:16:42.520 a lot of criticism about gene therapy in general. So 0:16:42.760 --> 0:16:47.080 even the people who were following very stringent, strict scientific 0:16:47.160 --> 0:16:52.120 processes and being as ethical as possible were brought under 0:16:52.480 --> 0:16:54.680 the microscope, and there were a lot of questions about 0:16:54.680 --> 0:16:58.760 when is it actually acceptable to move from the experimental 0:16:58.800 --> 0:17:02.280 stage where your work ing on some isolated tissue or 0:17:02.320 --> 0:17:05.760 you're working with an animal not a human being, UH, 0:17:05.800 --> 0:17:08.159 and then move that to human trials, When is that 0:17:08.280 --> 0:17:13.080 actually an acceptable moment in gene therapy? And the whole 0:17:13.119 --> 0:17:16.119 thing kind of brought the discipline to a crawl for 0:17:16.160 --> 0:17:18.240 a couple of years, and there's still a lot of 0:17:18.240 --> 0:17:22.920 scrutiny there obviously, because this is this is potentially very 0:17:23.000 --> 0:17:26.840 useful but also very dangerous type stuff. In two thousand two, 0:17:26.880 --> 0:17:31.680 researchers at Case Western Reserve University and Copernicus Therapeutics created 0:17:31.680 --> 0:17:35.960 the liposomes UH that there were twenty five nanometers across, 0:17:36.240 --> 0:17:40.200 so a nanometer is one billionth of a meter. That's 0:17:40.240 --> 0:17:44.000 incredibly tiny, and that they wanted to use to carry 0:17:44.040 --> 0:17:47.439 therapeutic DNA through pores in the nuclear membrane. And that 0:17:47.560 --> 0:17:50.840 same year, sickle cell disease was treated in mice using 0:17:50.880 --> 0:17:53.480 gene therapy for the first time and showing that that 0:17:53.520 --> 0:17:56.639 could be an effective treatment. Two thousand three, the University 0:17:56.680 --> 0:18:01.280 of California used liposomes coated in paul ethylene glycol. That's 0:18:01.320 --> 0:18:04.840 what I was talking about earlier, the PEG material, which 0:18:05.320 --> 0:18:07.639 that was determined to be a good vector for delivering 0:18:07.680 --> 0:18:11.840 gene therapy to the brain because again most viruses, not all, 0:18:11.920 --> 0:18:15.119 but most viruses are too large to penetrate the blood 0:18:15.119 --> 0:18:18.640 brain barrier. And then in two thousand six, National Institutes 0:18:18.640 --> 0:18:22.160 of Health used gene therapy to treat melanoma and showed 0:18:22.200 --> 0:18:23.919 for the first time that gene therapy could be a 0:18:24.000 --> 0:18:28.760 viable treatment for cancer. Now that's the history. Lesson, let's 0:18:28.760 --> 0:18:32.439 talk about what's going on kind of around that time too. 0:18:32.480 --> 0:18:36.160 More recent. I want to stress that when I look 0:18:36.200 --> 0:18:39.960 at information about gene therapy, I still very often see 0:18:40.560 --> 0:18:44.680 phrases like last resort, right I think that usually these 0:18:44.680 --> 0:18:47.400 experiments and and this research that's going on is on 0:18:47.840 --> 0:18:51.600 children with terrible fatal diseases, and and so frequently it 0:18:51.680 --> 0:18:53.960 is it is a last resort, right, and its and 0:18:54.000 --> 0:18:57.280 it's just well, I just wanted to stress this. Despite 0:18:57.320 --> 0:19:00.000 the fact that we have moved past some of these 0:19:00.040 --> 0:19:02.480 early days, like, there's still a whole lot of caution 0:19:02.520 --> 0:19:05.119 about it, and there should be. I mean, because again, 0:19:05.440 --> 0:19:08.960 we there's still so much we don't understand that that 0:19:09.040 --> 0:19:11.560 it needs. We need to have caution, not only just 0:19:11.720 --> 0:19:15.080 to be ethical and safe and give the patient as 0:19:15.119 --> 0:19:19.159 good a chance at recovery or treatment as possible, but 0:19:19.240 --> 0:19:21.760 also just so we keep our own expectations in check 0:19:21.840 --> 0:19:24.439 and we don't sit there and think, oh, if I 0:19:24.560 --> 0:19:27.480 just change out this one little strand of information within 0:19:27.520 --> 0:19:31.080 this person's cells, everything's going to be fine. Uh. It's 0:19:31.200 --> 0:19:33.399 it's important to realize that there's so much we don't 0:19:33.440 --> 0:19:38.080 know that we have to proceed with caution, because until 0:19:38.200 --> 0:19:41.800 we know all that information, we could potentially do more 0:19:41.800 --> 0:19:45.080 harm than good in our treatment. Yeah. One of the 0:19:45.280 --> 0:19:51.000 uh interesting studies I found was related to vaccines. So 0:19:52.359 --> 0:19:56.200 right now a vaccine is pretty much always preferable as 0:19:56.240 --> 0:19:59.359 the way to prevent somebody from contracting a disease. Sure, 0:20:00.040 --> 0:20:02.960 but what about in the case of a disease where 0:20:03.119 --> 0:20:08.640 we just can't get a reliable vaccine like HIV UM Now, 0:20:08.760 --> 0:20:13.040 the human immunodeficiency virus, it's difficult to create a vaccine 0:20:13.119 --> 0:20:17.000 because of the structure of the virus. Antibodies have to 0:20:17.720 --> 0:20:22.040 recognize elements on the external structure of a virus UM 0:20:22.080 --> 0:20:24.760 to in order to want to attack it, to to 0:20:24.840 --> 0:20:28.239 recognize it and prevent it UM. But HIV is kind 0:20:28.280 --> 0:20:31.159 of stealth. It doesn't have those external structures, which is 0:20:31.200 --> 0:20:34.320 difficult to recognize UM. And so there's been all this 0:20:34.400 --> 0:20:39.600 difficulty creating a vaccine. But some recent research, especially some 0:20:39.600 --> 0:20:43.080 stuff published in Nature in two thousand eleven, found that, well, 0:20:43.480 --> 0:20:48.000 at least in a trial on mice, the immuno deficiency 0:20:48.119 --> 0:20:53.600 virus is susceptible to gene therapy that would prevent transmission UM, 0:20:53.680 --> 0:20:57.360 and so a gene therapy could be sort of like 0:20:57.400 --> 0:21:02.720 a preventative measure to keep you from contracting HIV. Of course, 0:21:03.080 --> 0:21:05.560 the trouble is, as with all these other cases we've 0:21:05.600 --> 0:21:08.200 been talking about, it it's it's dangerous basically, right, and 0:21:08.480 --> 0:21:11.880 there there are other diseases and conditions where we have 0:21:13.080 --> 0:21:16.119 little to no treatment right now, Like it may be 0:21:16.280 --> 0:21:18.520 that all we can do is treat some symptoms, but 0:21:18.560 --> 0:21:22.800 we can't treat anything that's underlying that. So everything from 0:21:23.040 --> 0:21:26.080 Parkinson's to Alzheimer's, that these kind of a lot of 0:21:26.080 --> 0:21:29.800 blood blood related genetic disorders right a lot of these 0:21:29.840 --> 0:21:32.439 different genetic disorders, we really have no way of treating 0:21:32.480 --> 0:21:35.560 anything beyond some symptoms in some cases, like in some 0:21:35.640 --> 0:21:38.560 we don't even have ways of treating the symptoms necessarily. 0:21:38.720 --> 0:21:41.000 So that's one of those things that people are really 0:21:41.000 --> 0:21:46.040 looking at. Gene therapy is potentially being another attempt to uh, 0:21:46.080 --> 0:21:50.119 to treat something that otherwise we pretty much can only 0:21:50.200 --> 0:21:53.399 just try and and and increase the patient's comfort as 0:21:53.440 --> 0:21:55.480 much as possible because there's nothing else we can do. 0:21:56.160 --> 0:21:58.040 Um in those cases, I think are the ones that 0:21:58.040 --> 0:22:00.600 are going to have the most attention to acted at 0:22:00.640 --> 0:22:05.040 them for the near term. For gene therapy. Absolutely, I 0:22:05.560 --> 0:22:08.760 wanted to correct myself really quick, really quickly from from earlier. 0:22:08.840 --> 0:22:13.679 Lenty viruses are a genus within the retrovirus family, but 0:22:13.760 --> 0:22:17.560 they but they're they're specific properties are important. I was 0:22:17.560 --> 0:22:19.720 talking about them like they're two totally different things. That is, 0:22:19.800 --> 0:22:23.879 that is an untruth right there. I knew that, No, 0:22:24.000 --> 0:22:27.960 I didn't so in all these cases, and especially because 0:22:28.000 --> 0:22:32.080 the science is still pretty preliminary. We're talking about last resort, 0:22:32.160 --> 0:22:35.040 we're talking about it's still something we're not very sure about, 0:22:35.080 --> 0:22:38.560 and we were only using cases where there's no other option. Really, right, 0:22:39.400 --> 0:22:41.680 But what if we got a lot better at it, sure, 0:22:42.000 --> 0:22:44.160 to the point where we can actually treat these diseases, 0:22:45.000 --> 0:22:49.159 people can lead healthy lives. These genetic disorders become a 0:22:49.200 --> 0:22:51.560 thing of the past. I see the future you're painting, right, 0:22:51.600 --> 0:22:55.399 and so its future where gene therapy is just completely safe. 0:22:55.480 --> 0:22:58.439 It's run of the mill. It's it's like vaccines are today. 0:22:58.600 --> 0:23:02.080 So you know, your chance of having a problem is 0:23:02.560 --> 0:23:06.680 one in some huge number. And we're having a sporting 0:23:06.800 --> 0:23:10.840 stars cheating by having gene therapy to make their blood 0:23:10.840 --> 0:23:14.920 more oxygen absorbent. Exactly. Oh well, well, guys, you're you're 0:23:14.960 --> 0:23:16.840 like totally I was. I was right there in the 0:23:16.880 --> 0:23:20.240 happy future where everybody was healthy, and now you're you're 0:23:20.240 --> 0:23:22.600 twisting it. What's going on? You're talking about gene doping. 0:23:22.680 --> 0:23:25.639 Gene doping, tell me about gene doping, Lauren, Well, gene 0:23:25.640 --> 0:23:29.720 doping doesn't exist right now, but we're we're afraid could 0:23:29.760 --> 0:23:32.840 happen in some kind of terrible future. Is is that? Yes? 0:23:32.920 --> 0:23:35.320 That that that people would use gene therapy in order to, 0:23:36.000 --> 0:23:37.439 you know, do do the same kind of things that 0:23:37.480 --> 0:23:40.880