WEBVTT - Ep 69 Huntington’s disease: Let’s talk frankly 0:00:01.280 --> 0:00:05.920 My name is Jay, and I am thirty four years old, 0:00:05.960 --> 0:00:11.440 and I was recently diagnosed with Huntington's disease. My grandfather 0:00:12.560 --> 0:00:17.040 was diagnosed with Huntington's in his eighties, but I don't 0:00:17.160 --> 0:00:21.200 think he and my grandmother really understood this, you know, 0:00:21.280 --> 0:00:25.840 severity of the illness and its implications for their children 0:00:26.000 --> 0:00:31.120 and grandchildren. So they never really told us until my 0:00:31.280 --> 0:00:38.520 father started seeing some symptoms in his fifties. So that's 0:00:38.640 --> 0:00:42.200 when I found out. I guess I was twenty eight, 0:00:42.760 --> 0:00:48.479 I'd just been married, you know, there's so much optimism, 0:00:48.640 --> 0:00:52.800 and then I find out for my parents that there's 0:00:52.920 --> 0:00:56.720 this terrible shadow, you know, that's going to be potentially 0:00:56.920 --> 0:01:02.040 hanging over my life. And it was. 0:01:01.960 --> 0:01:05.800 Definitely really, really hard. I'm not gonna lie. 0:01:06.480 --> 0:01:12.280 Your priorities sort of shift, just trying to maximize the 0:01:12.440 --> 0:01:15.720 years that you might have with a good quality of life, 0:01:15.880 --> 0:01:22.000 you know. So I didn't get tested right away. I 0:01:22.160 --> 0:01:27.679 really wasn't ready. But over the years I started to, 0:01:28.200 --> 0:01:32.880 I guess, come to a point of acceptance, and I 0:01:32.920 --> 0:01:39.200 also started to see symptoms starting to appear, things like 0:01:40.040 --> 0:01:49.320 coordination issues, balance issues, also difficulty swallowing and drinking. So 0:01:49.480 --> 0:01:53.000 that's how it's starting to affect me, and it got 0:01:53.000 --> 0:01:55.680 to a point where I was ready to be tested, 0:01:56.120 --> 0:01:58.080 and so I did that, I guess a few months 0:01:58.120 --> 0:02:04.840 ago actually, and now I have the official results that 0:02:05.000 --> 0:02:09.240 I'm positive for a huntidian disease. At that point, I 0:02:09.240 --> 0:02:11.920 guess it wasn't as bad as I thought. Actually, to 0:02:12.000 --> 0:02:17.679 get those words for me, it was, I guess, a 0:02:17.720 --> 0:02:24.680 little bit freeing to finally have some solid answers and 0:02:25.520 --> 0:02:29.919 to know what my reality would be. You know, I'm 0:02:29.960 --> 0:02:33.239 really lucky to have a really supportive husband with me. 0:02:34.800 --> 0:02:37.480 He's been a rock for every step of the way, 0:02:39.000 --> 0:02:43.720 being understanding for all my decisions. One in particular is 0:02:43.760 --> 0:02:48.560 that I feel really strongly that I don't want to 0:02:48.600 --> 0:02:53.120 pass this on to my children. I know that's maybe 0:02:53.120 --> 0:03:01.160 a controversial opinion, but I just can't imagine potentially burgeoning 0:03:01.200 --> 0:03:07.480 them with this same difficulties that I'm experiencing. So we'll 0:03:07.520 --> 0:03:13.240 be using IVF. They have this cool technology where they 0:03:13.240 --> 0:03:17.480 can test the embryos, and that's the route we'll be taking. 0:03:18.960 --> 0:03:24.800 But obviously it's also time consuming and expensive and not 0:03:25.040 --> 0:03:26.119 a guarantee. 0:03:26.400 --> 0:03:27.880 So it's. 0:03:29.000 --> 0:03:32.600 One of the most disappointing things about this diagnosis is 0:03:33.080 --> 0:03:35.280 one of the few things I really knew I wanted 0:03:36.080 --> 0:03:38.080 was a baby, and. 0:03:39.800 --> 0:03:41.600 Now we can't just conceive. 0:03:41.280 --> 0:03:44.680 The natural way. We've got to go through all these hurls. 0:03:46.720 --> 0:03:49.880 Another aspect about it that's really difficult is because it's 0:03:49.880 --> 0:03:55.280 a family disease. You see, I saw my grandfather suffer 0:03:55.280 --> 0:03:58.160 from it, and now my father is suffering from it, 0:03:58.240 --> 0:04:01.560 and now I'm going to have the same symptoms, and 0:04:01.680 --> 0:04:09.240 my aunt also possibly my brothers. So it's really difficult 0:04:10.160 --> 0:04:12.360 to not feel like you're being a burden if you 0:04:12.440 --> 0:04:19.480 want to, you know, share your feelings with your family 0:04:19.520 --> 0:04:25.599 members and reach out to them without being potentially a 0:04:25.640 --> 0:04:30.480 burden to them when they are also dealing with this 0:04:30.560 --> 0:04:33.359 kind of stress, and also being a burden to my husband. 0:04:33.400 --> 0:04:38.599 Of course, eventually you know he'll be caring for me 0:04:38.839 --> 0:04:39.520 more and more. 0:04:41.480 --> 0:04:45.719 So Yeah, it's really really hard. 0:04:49.160 --> 0:04:53.760 Hi, this is Jay's husband. Some of the difficult things 0:04:53.800 --> 0:04:58.719 are trying to explain to say, my side of the family, 0:04:59.400 --> 0:05:04.800 what's going on on. My sisters have their families going along, 0:05:05.200 --> 0:05:08.920 and things like that. And at this point we've had 0:05:08.960 --> 0:05:12.640 your diagnosis, I guess for more than more than a month, 0:05:13.839 --> 0:05:19.679 but we still haven't found the right time or place 0:05:20.160 --> 0:05:26.320 or way to even tell our extended families or my 0:05:26.440 --> 0:05:31.240 family even. I think basically for you, it's just it's 0:05:31.400 --> 0:05:37.120 just your immediate family on one side that we've really 0:05:37.160 --> 0:05:41.800 talked to about it. But we don't even know how 0:05:41.880 --> 0:05:51.440 to tell our friends about this because we just don't 0:05:51.480 --> 0:05:53.600 have we don't have the words, and we don't know 0:05:53.600 --> 0:05:57.800 how to. I guess like we're not looking for sympathy, 0:05:58.120 --> 0:06:00.200 but we also don't. It's we don't want to keep 0:06:00.200 --> 0:06:06.840 it a secret, and given that it's not something that 0:06:07.880 --> 0:06:12.880 can be cured like cancer or COVID, this is something 0:06:13.279 --> 0:06:16.440 that is not going away, and I think that has 0:06:16.800 --> 0:06:21.560 been one of the really stressful parts. We haven't really 0:06:21.640 --> 0:06:25.640 figured out a good way to to share with it 0:06:26.040 --> 0:06:30.040 with those that are even closest to us. I think 0:06:30.160 --> 0:06:35.960 that has definitely weighed on me. At least two have 0:06:36.040 --> 0:06:41.680 this information and not be able to really talk to 0:06:41.720 --> 0:06:46.000 people about it yet because just we don't know how. 0:06:47.960 --> 0:06:52.200 Another thing that we've kind of been thinking a lot 0:06:52.240 --> 0:06:55.520 about is just, you know, like, what do we do 0:06:56.960 --> 0:07:03.119 right Unlike some diseases again that do have cures, when 0:07:03.320 --> 0:07:08.880 do we need to tell insurance? Because we definitely will 0:07:08.920 --> 0:07:12.120 want some of you know all as much of the 0:07:12.200 --> 0:07:15.920 care to be covered by insurance, but that's not something 0:07:16.080 --> 0:07:19.680 that a lot of people have been able to give 0:07:19.760 --> 0:07:23.800 us advice on, or there's not a good rule book 0:07:23.880 --> 0:07:28.000 or a guidebook out there. And because everybody's path with 0:07:28.120 --> 0:07:32.080 hunting teens is different than the solutions and how they 0:07:32.160 --> 0:07:35.600 resolve it are all different. I think one of the 0:07:35.920 --> 0:07:41.400 really difficult parts is that Jay's grandfather showed symptoms in 0:07:41.440 --> 0:07:45.400 his eighties, and his path and how he dealt with 0:07:45.440 --> 0:07:48.480 it was very different than her father, who was in 0:07:48.480 --> 0:07:52.320 his fifties when he was diagnosed, and that's very different 0:07:52.640 --> 0:07:58.760 from Jay, who started displaying symptoms in her thirties. And 0:07:59.240 --> 0:08:06.320 so there's even when we look for comparisons to how 0:08:06.360 --> 0:08:09.880 to manage and how to deal with it, we don't 0:08:09.920 --> 0:08:14.120 have a particularly good role model or something to compare to, 0:08:14.960 --> 0:08:19.120 and we're kind of going at our own pace, in 0:08:19.160 --> 0:08:21.840 our own direction and hoping that we get it right, 0:08:22.040 --> 0:08:25.840 but also being really aware that we don't have a 0:08:25.840 --> 0:08:27.880 lot of flexibility that we have to get it right 0:08:27.920 --> 0:08:30.840 the first time, because all these days are precious. 0:08:32.400 --> 0:08:36.160 Yeah, I guess that's definitely a downside of it being 0:08:36.160 --> 0:08:43.079 a relatively very disease unlike something like breast cancer. There's 0:08:43.280 --> 0:08:48.079 just not as much resources. There's not like, you know, 0:08:48.240 --> 0:08:51.160 the kind of community that you get when you're diagnosed 0:08:51.160 --> 0:08:56.440 with cancer. Let's say, there's not as much research, not 0:08:56.520 --> 0:09:04.200 as much funding. So yeah, I guess overall, I've been 0:09:04.360 --> 0:09:07.640 trying to just you know, do it day by day, 0:09:08.000 --> 0:09:11.959 a little by little. Some days are good, some days 0:09:12.040 --> 0:09:17.760 are bad. But it's my reality now. And you don't 0:09:17.800 --> 0:09:20.520 really have a choice anymore, right, You just have to. 0:09:21.760 --> 0:09:25.000 You're on the train, so you kind of have to 0:09:25.040 --> 0:09:29.520 deal with it. And I guess that's been how I'm 0:09:29.559 --> 0:09:32.880 trying to look at it, and hopefully I can just 0:09:33.000 --> 0:09:40.320 keep some optimism as things progress, you know, despite what 0:09:40.440 --> 0:09:40.880 might come. 0:10:26.520 --> 0:10:29.760 Thank you so so much for sharing your story with us. 0:10:30.120 --> 0:10:31.679 We really appreciate it. 0:10:32.280 --> 0:10:33.040 Yeah, thank you. 0:10:34.200 --> 0:10:34.400 Hi. 0:10:34.640 --> 0:10:37.800 I'm Aaron Welsh and I'm Aaron Allman Updike. 0:10:37.679 --> 0:10:40.000 And this is this podcast Will Kill You. 0:10:40.720 --> 0:10:45.840 And today we're talking about Huntington's disease. Yes we are. 0:10:46.480 --> 0:10:48.640 This is just one of a handful of the genetic 0:10:48.679 --> 0:10:51.280 diseases that we have covered, Aaron, right. 0:10:51.160 --> 0:10:54.600 Yes it is, and it's very different than the other 0:10:55.320 --> 0:10:57.319 genetic disorders that we've covered so far. 0:10:57.600 --> 0:11:00.600 So yeah, I mean, this is a big top to cover. 0:11:00.760 --> 0:11:04.680 So yeah, yeah, so let's like maybe get right down 0:11:04.679 --> 0:11:05.320 to business. 0:11:05.559 --> 0:11:07.120 I think that business we should cover. 0:11:07.520 --> 0:11:07.840 Yeah. 0:11:07.880 --> 0:11:11.160 The first business, as always is quarantiny time. 0:11:11.559 --> 0:11:16.120 It's quarantiny time, and this week we are drinking the Marjorie. 0:11:16.440 --> 0:11:21.920 The Marjorie named for Marjorie Guthrie, who was the founder 0:11:22.040 --> 0:11:25.199 of one of the of one of the biggest Huntington's 0:11:25.200 --> 0:11:29.600 Disease advocacy groups in the US, now called the Huntington's 0:11:29.640 --> 0:11:31.640 Disease Society of America. 0:11:31.200 --> 0:11:35.160 I believe excellent. And what is in the Marjorie. 0:11:34.840 --> 0:11:41.200 The Marjorie is vodka, orange juice, unsweetened crimeberry juice, and 0:11:41.320 --> 0:11:42.720 a little bit of amaretto. 0:11:43.480 --> 0:11:44.080 Excellent. 0:11:44.720 --> 0:11:47.880 We'll post the full recipe for that quarantini as well 0:11:47.920 --> 0:11:51.120 as our non alcoholic Plussy berita on our website. This 0:11:51.200 --> 0:11:53.000 podcast will kill You dot Com and all of our 0:11:53.040 --> 0:11:58.600 social media channels as always, and the usual business. I 0:11:58.600 --> 0:11:59.360 guess you know. 0:11:59.679 --> 0:12:02.280 We have transcripts, which is thrilling. 0:12:02.760 --> 0:12:03.160 Thrilling. 0:12:03.320 --> 0:12:05.160 You can find those on the Transcripts to Have of 0:12:05.160 --> 0:12:07.679 our website, and on our website you can also find 0:12:07.800 --> 0:12:10.840 all kinds of other fun things like a good Reads list, 0:12:11.000 --> 0:12:13.160 or a link to a good Reads list, a link 0:12:13.200 --> 0:12:16.800 to our bookshop affiliate page, any of the sources that 0:12:16.840 --> 0:12:21.520 we use in all of our episodes. Linked to Bloodmobiles 0:12:21.640 --> 0:12:23.800 music page on band camp. I mean, it's all there. 0:12:24.000 --> 0:12:25.560 Just check it out. You'll have a fun time. 0:12:25.760 --> 0:12:33.440 It's a very fun time website. All right, Well, this is, 0:12:33.520 --> 0:12:37.360 as you said, Erin, it's a very big topic. So 0:12:38.080 --> 0:12:40.800 shall we take a quick break and then dive right in. 0:12:41.120 --> 0:13:18.199 Let's do it. 0:13:11.400 --> 0:13:18.319 So right up front, Huntington's is a neurodegenerative genetic disorder 0:13:19.400 --> 0:13:23.920 that is inherited in an autosomal dominant fashion. So what 0:13:23.960 --> 0:13:26.680 does that mean. It means that this is a disorder 0:13:26.679 --> 0:13:31.960 that's affecting the brain and the nervous system, and you 0:13:32.080 --> 0:13:35.160 only need one copy of the mutated gene in order 0:13:35.200 --> 0:13:38.320 to have disease. So that's already different from the other 0:13:38.360 --> 0:13:41.280 two genetic disorders that we've covered in the past, namely 0:13:41.320 --> 0:13:45.920 sickle cell and cystic fibrosis, which are both autosomal recessive, 0:13:46.000 --> 0:13:48.199 so you have to have two copies of a mutated 0:13:48.240 --> 0:13:53.120 gene in order to have disease. But before we can 0:13:53.160 --> 0:13:57.840 actually talk about Huntington's disease, I think we need to 0:13:57.880 --> 0:14:02.160 step back and talk about our genes in more detail 0:14:02.240 --> 0:14:05.760 than I think we have on this podcast, at least recently. 0:14:06.440 --> 0:14:10.400 So here's where road begin. Our DNA is made up 0:14:10.480 --> 0:14:15.200 of little building blocks like legos, called nucleotides, which we 0:14:15.280 --> 0:14:19.640 give letters A, T, C, and G. So three of 0:14:19.680 --> 0:14:24.640 these nucleotides grouped together form what's called a codeon because 0:14:24.720 --> 0:14:29.400 that is what codes for an amino acid. Well, it 0:14:29.440 --> 0:14:31.800 codes for RNA, which codes for amino acids, but will 0:14:31.800 --> 0:14:35.000 ignore them. Right, Okay, when you string a bunch of 0:14:35.040 --> 0:14:39.840 amino acids together, you get essentially a protein scattered throughout 0:14:40.000 --> 0:14:43.840 our genome. Throughout not just human genomes, but like every 0:14:43.960 --> 0:14:50.080 genome animals, plants, bacteria. We have these short repeat sequences 0:14:50.280 --> 0:14:55.200 of nucleotides that are called microsatellites. They are like one 0:14:55.240 --> 0:14:59.880 to six nucleotide sequences that are repeated like tata ta, 0:15:00.200 --> 0:15:06.600 all in a row. So that's some basic definitions. Now 0:15:06.720 --> 0:15:09.080 on this podcast we talk a lot, usually in the 0:15:09.080 --> 0:15:13.000 context of viruses or bacteria, but this is true for 0:15:13.120 --> 0:15:17.440 human cells too. How every time our cells or any 0:15:17.480 --> 0:15:22.200 cell replicates, it sometimes makes mistakes, and we call these 0:15:22.240 --> 0:15:28.200 mistakes mutations. Most of the time, these mutations result in 0:15:28.280 --> 0:15:32.400 like a single or small base pair change like one 0:15:32.560 --> 0:15:36.120 addition or a deletion, or a substitution like a T 0:15:36.400 --> 0:15:41.680 for an A or something like that. But within these 0:15:41.920 --> 0:15:47.400 repeat regions, these microsatellite regions, a single mistake can lead 0:15:47.600 --> 0:15:51.960 to very big changes because what it often leads to 0:15:52.280 --> 0:15:56.880 is the gain or the loss of an entire repeat sequence. 0:15:58.520 --> 0:16:02.960 So how does that happen. We don't fully know, but 0:16:03.960 --> 0:16:07.600 we think that what happens is that as our DNA 0:16:07.640 --> 0:16:11.080 polymerase that's helping to replicate our DNA is chugging along 0:16:11.160 --> 0:16:15.400 copying tatata all in a row, it kind of slips 0:16:15.480 --> 0:16:18.240 out of position and then it loses its place, and 0:16:18.280 --> 0:16:21.080 when it picks it back up, it does so earlier 0:16:21.200 --> 0:16:24.520 along that DNA chain. So if you have a region 0:16:24.560 --> 0:16:27.320 that's like TATA four times in a row and it 0:16:27.360 --> 0:16:31.200 gets a little bit wonky during replication, the next cell 0:16:31.920 --> 0:16:35.520 as after it replicates, would end up with TATA like 0:16:35.680 --> 0:16:38.000 six times in a row or eight times in a row. 0:16:39.240 --> 0:16:44.880 So that's microsatellites. They exist throughout our genome, and the 0:16:45.000 --> 0:16:48.240 mutation rate tends to be higher in these repeat regions 0:16:48.640 --> 0:16:51.960 than in other parts of our genome. And the longer 0:16:52.040 --> 0:16:55.480 a microsatellite region is, the more likely it is that 0:16:55.560 --> 0:16:59.800 this type of slippage and mutation can happen, and the 0:17:00.000 --> 0:17:04.000 more likely that the mutation results in large changes, especially 0:17:04.400 --> 0:17:08.760 expansion or growing of those regions and getting longer. So 0:17:08.880 --> 0:17:13.800 let's talk about how that relates to Huntington's disease. Yeah, 0:17:14.200 --> 0:17:18.600 Huntington's disease is a disorder that's known as a trinucleotide 0:17:18.800 --> 0:17:23.119 repeat disorder, So that means it's caused by an abnormal 0:17:23.200 --> 0:17:27.760 number of trinucleotide three nucleotides in a row C, A, 0:17:28.080 --> 0:17:31.480 and G that repeat a whole bunch of times. Aka, 0:17:31.680 --> 0:17:34.000 this is a microsatellite. 0:17:33.160 --> 0:17:40.400 And there are other diseases that are this trinucleotide repeat diseases. 0:17:40.040 --> 0:17:43.399 Right, absolutely, yes. So fragile X is another example of 0:17:43.400 --> 0:17:47.399 a trinucleotide repeat disorder where you have a repeat at 0:17:47.400 --> 0:17:52.160 the end of the X chromosome. You also have Friedrich's ataxia, 0:17:52.840 --> 0:17:57.760 there's muscular dystrophe. There's a whole host of trinucleotide repeat disorders. 0:17:58.480 --> 0:18:03.600 This is one and this happens in a gene that 0:18:03.640 --> 0:18:07.399 we all have on chromosome four that's called the Huntington gene, 0:18:08.440 --> 0:18:12.440 where on chromosome four. There's a series. In everyone where 0:18:12.480 --> 0:18:16.119 we have this microsatellite, we have these CAG repeats, But 0:18:16.240 --> 0:18:19.920 in the vast majority of the population we have anywhere 0:18:19.960 --> 0:18:25.800 from five to like twenty eight copies of CAG all 0:18:25.840 --> 0:18:31.840 in a row. And another thing that's important about this 0:18:32.000 --> 0:18:35.840 repeat on chromosome four is that it's located in what's 0:18:35.880 --> 0:18:38.919 called an exon or a coding region, which means that 0:18:39.040 --> 0:18:43.480 our body, every human body and other animals too, we 0:18:43.600 --> 0:18:48.120 make a protein from this region that's called Huntington that's 0:18:48.359 --> 0:18:51.680 really clever name. But now we know that these microsatellite 0:18:51.720 --> 0:18:56.040 regions can sometimes be unstable and expand, And it turns 0:18:56.080 --> 0:19:00.800 out that once you get to above twenty eight re repeats, 0:19:01.760 --> 0:19:05.920 that is when this region becomes unstable, and that means 0:19:05.920 --> 0:19:10.240 that when those cells replicate, that particular region is likely 0:19:10.320 --> 0:19:15.600 to expand. It could contract, but it's more likely to expand, 0:19:16.320 --> 0:19:20.920 and once it expands above forty repeats, that is when 0:19:20.920 --> 0:19:23.160 a person will develop Huntington's disease. 0:19:24.119 --> 0:19:27.040 Why forty what happens at that point? 0:19:27.320 --> 0:19:31.600 Okay, great question. So the why forty is an interesting 0:19:31.680 --> 0:19:35.760 question because it could be a little bit earlier than forty. 0:19:37.080 --> 0:19:40.639 It really doesn't ever happen any earlier than thirty six, 0:19:40.880 --> 0:19:44.040 but especially that high thirty region, you can have what's 0:19:44.080 --> 0:19:48.199 called incomplete penetrants, where some people with that number of 0:19:48.200 --> 0:19:51.120 repeats might have disease and others might not. So that's 0:19:51.160 --> 0:19:55.720 kind of like a gray zone. But essentially, the reason 0:19:55.880 --> 0:19:59.399 why once you have a certain number of repeats you 0:19:59.560 --> 0:20:04.280 end up with disease is because that trinucleotide repeat is 0:20:04.400 --> 0:20:08.280 located in an exxon in a coding region, So that 0:20:08.480 --> 0:20:13.000 abnormally long set of repeats causes the production of an 0:20:13.119 --> 0:20:19.600 abnormal Huntington protein, and the more this repeat expands, the 0:20:19.760 --> 0:20:25.760 more abnormal this protein is, and probably the more abnormal 0:20:25.800 --> 0:20:27.639 protein you are producing as well. 0:20:28.320 --> 0:20:30.639 Okay, so what does this protein do? 0:20:31.119 --> 0:20:36.399 Okay, very good question. I'm not going to answer this 0:20:36.480 --> 0:20:42.600 satisfactorily because the answer is normally we don't know. So 0:20:43.040 --> 0:20:47.520 we know that this Huntington protein is essential to development 0:20:47.960 --> 0:20:51.320 because if you knock it out completely in mice, they 0:20:51.359 --> 0:20:56.040 don't live, like, they don't develop in utero and they die. 0:20:56.240 --> 0:20:59.800 So we know that this protein does something that's very important. 0:21:00.080 --> 0:21:04.000 We think that it's involved with like trafficking of stuff 0:21:04.119 --> 0:21:07.359 inside of the cell, like moving things from one place 0:21:07.400 --> 0:21:10.240 to another within the cell, within a cell, within a cell. 0:21:10.960 --> 0:21:13.280 But we don't know that for sure. We don't know 0:21:13.960 --> 0:21:19.159 the real function of normal, typical what they call wild 0:21:19.280 --> 0:21:23.520 type Huntington protein. But that still doesn't answer the question 0:21:23.560 --> 0:21:26.359 of like, how does this actually cause disease? Like, Okay, 0:21:26.400 --> 0:21:33.600 we have an abnormal protein, so what Yeah, the short answer, 0:21:33.640 --> 0:21:36.160 I'm going to try and give the shorter answer, even 0:21:36.200 --> 0:21:40.320 though I think it's going to be less satisfying. Don't 0:21:41.280 --> 0:21:44.840 we don't really know. 0:21:44.960 --> 0:21:47.240 That's not satisfying, give me the longer answer. 0:21:47.320 --> 0:21:51.320 I warned you, we don't fully know. There's a lot 0:21:51.320 --> 0:21:55.400 of hypotheses about the like specific cellular mechanisms that are 0:21:55.440 --> 0:21:59.560 involved with this abnormal protein. We have a lot of 0:21:59.640 --> 0:22:03.000 evidence that it's what's called a gain of function. So 0:22:04.160 --> 0:22:07.440 in for example, our cystic fibrosis episode, we talked about 0:22:07.480 --> 0:22:10.640 how when you have a mutation in the cystic fibrosis protein, 0:22:11.000 --> 0:22:13.480 you lose the function of that protein and that's what 0:22:13.600 --> 0:22:19.120 causes disease. Here we have the opposite where the production 0:22:19.440 --> 0:22:22.919 of this abnormal protein is what's involved. It's not that 0:22:23.520 --> 0:22:28.040 the Huntington protein is no longer doing whatever Huntington protein 0:22:28.080 --> 0:22:30.680 is supposed to do. It's that it's doing something new 0:22:31.000 --> 0:22:31.880 and different and. 0:22:31.800 --> 0:22:33.520 Bad, right, Okay. 0:22:33.720 --> 0:22:37.880 So we know that the accumulation of this abnormal protein 0:22:38.160 --> 0:22:42.360 it forms aggregates, it forms these beta pleated sheets, they 0:22:42.400 --> 0:22:47.520 aggregate into cells, and then also possibly the mRNA itself 0:22:47.560 --> 0:22:51.280 that codes for this protein is somehow toxic to our 0:22:51.359 --> 0:22:56.480 cells and it causes cell death. So that's the end result. 0:22:56.640 --> 0:23:00.480 Is what happens is cells die because of this abnormal protein. 0:23:02.440 --> 0:23:06.399 And while Huntington protein is found kind of throughout our body, 0:23:06.520 --> 0:23:08.639 like this gene is expressed in a lot of different 0:23:08.640 --> 0:23:15.160 tissues for whatever reason, this abnormal protein causes damage primarily 0:23:15.240 --> 0:23:19.400 to the central nervous system. So that's why we see 0:23:19.400 --> 0:23:23.520 this as a neurodegenerative disease, because it's causing cell death 0:23:24.000 --> 0:23:24.840 in neurons. 0:23:25.240 --> 0:23:27.880 Is it expressed more highly there or what's happening? 0:23:28.760 --> 0:23:33.040 Good question? Don't fully know? Okay, at least I don't 0:23:33.040 --> 0:23:37.760 fully know. We can get even more specific, and getting 0:23:37.760 --> 0:23:40.840 more specific will help us to understand the symptoms of 0:23:40.920 --> 0:23:46.120 Huntington's disease itself, because we know the cells in our 0:23:46.160 --> 0:23:49.320 brain that are the most affected. One of the main 0:23:49.359 --> 0:23:52.360 areas that we see the loss of neurons, and damage 0:23:52.359 --> 0:23:56.320 to neurons is in the striatum of the basal ganglia. 0:23:56.840 --> 0:24:01.800 So while we do see eventures the entire brain becoming 0:24:01.840 --> 0:24:06.959 involved and like widespread atrophy, this striatum of the basil 0:24:06.960 --> 0:24:11.080 ganglia is the first and hardest hit area. So what 0:24:11.160 --> 0:24:14.800 is the basil ganglia? We actually talked about this way 0:24:14.880 --> 0:24:19.080 back in our encephalitis lethargic at episode a million years ago. 0:24:19.359 --> 0:24:20.000 Do you remember that? 0:24:20.320 --> 0:24:25.080 Uh uh yeah, yeah don't I don't remember. 0:24:25.760 --> 0:24:29.680 Okay, well, let me tell you then. The basil ganglia. 0:24:29.840 --> 0:24:32.280 It's a set of brain structures that are deep in 0:24:32.359 --> 0:24:39.760 our forebrain that essentially helped to control movement. So the 0:24:39.760 --> 0:24:44.160 basil ganglia helps to coordinate inputs from the motor cortex 0:24:44.160 --> 0:24:47.840 of our brain. They process them and then they put 0:24:47.880 --> 0:24:50.840 outputs out to the thalamus and other places that go 0:24:51.000 --> 0:24:56.840 to our muscles and actually initiate smooth muscle movement, well 0:24:57.080 --> 0:24:59.840 skeletal muscle, but I mean like smooth, coordinated. 0:25:00.400 --> 0:25:01.120 Okay. 0:25:03.359 --> 0:25:05.920 It's also the basil ganglia is involved in a lot 0:25:05.960 --> 0:25:09.119 of other things like cognition and emotion. Like this is 0:25:09.160 --> 0:25:11.960 our brain, it's all very integrated, but one of the 0:25:12.000 --> 0:25:16.040 major functions is in this coordination of movement, and a 0:25:16.080 --> 0:25:19.480 lot of what the basil ganglia does specifically is actually 0:25:19.520 --> 0:25:25.560 to inhibit movements, so that when this basil ganglia is damaged, 0:25:25.680 --> 0:25:30.320 we lose that ability to inhibit movement, so movement becomes 0:25:30.480 --> 0:25:32.320 uncontrolled or uncoordinated. 0:25:32.720 --> 0:25:36.640 Okay, And is this a common structure that is damaged 0:25:36.640 --> 0:25:41.320 in other movement disorders like Parkinson's or something precisely? 0:25:41.560 --> 0:25:45.040 So, in Parkinson's, it's a different set of neurons and 0:25:45.080 --> 0:25:48.679 it they're more specific. And so that's why we actually 0:25:48.720 --> 0:25:53.760 have better treatments. We still don't have treatments to treat Parkinson's, 0:25:54.000 --> 0:25:56.680 but to treat the symptoms. We're better at Parkinson's that 0:25:56.720 --> 0:26:00.800 we are at Huntington's because of what is being damaged, 0:26:00.880 --> 0:26:04.160 but this region has more varied functions and so it's 0:26:04.200 --> 0:26:09.560 harder to target. Okay, gotcha. Yeah, So that finally brings 0:26:09.640 --> 0:26:14.400 us to the symptoms of Huntington's disease. The characteristic symptoms 0:26:14.680 --> 0:26:17.920 which gave Huntington's disease an earlier name that I'm sure 0:26:17.960 --> 0:26:23.679 you'll talk about, Aaron. The characteristic symptoms are Korea or 0:26:23.800 --> 0:26:30.000 Korea form movements. These are involuntary motor movements especially in 0:26:30.040 --> 0:26:33.280 the extremities, so like arms and legs, fingers, and toes, 0:26:34.640 --> 0:26:38.760 the involuntary movements, they're kind of like muscle twitches essentially 0:26:39.480 --> 0:26:42.520 that usually start out early in the course of disease 0:26:43.080 --> 0:26:48.640 in smaller muscles, so like fingers, face twitches that, especially 0:26:48.720 --> 0:26:52.480 early in disease might not be noticeable to anyone other 0:26:52.520 --> 0:26:55.280 than the person who's experiencing them, like you wouldn't even 0:26:55.320 --> 0:26:58.520 notice them, and they might not interfere very much at 0:26:58.560 --> 0:27:03.040 all with daily life. But eventually they spread to affect 0:27:03.359 --> 0:27:08.680 essentially any or every voluntary muscle, which includes the muscles 0:27:08.720 --> 0:27:13.440 of the face and the throat that are involved in talking, chewing, swallowing, 0:27:15.400 --> 0:27:20.359 and so then dysarthria, which is difficulty speaking, can become 0:27:20.400 --> 0:27:24.520 a problem, as well as dysphasia or difficulty swallowing and eating, 0:27:24.600 --> 0:27:26.199 which is very problematic. 0:27:26.680 --> 0:27:26.960 Yeah. 0:27:27.640 --> 0:27:32.560 And then eventually, as this disease progresses, this increase that 0:27:32.600 --> 0:27:36.720 we see in muscle movement actually transitions to what's called 0:27:36.920 --> 0:27:43.080 hypokinesia and Brady caynesia, which means slowing of muscle movement 0:27:43.680 --> 0:27:48.840 and less muscle movement, and this causes like a difficulty 0:27:49.040 --> 0:27:55.040 in initiating voluntary movement, so muscles become very rigid, and 0:27:55.080 --> 0:27:57.959 this is actually not unlike what we see in Parkinson's 0:27:58.000 --> 0:28:00.720 disease as well. You have a lot of rerigidity in 0:28:00.840 --> 0:28:06.320 Parkinson's disease, right, Yeah, So of course, all of these 0:28:06.440 --> 0:28:11.600 symptoms can have huge effects on a person's activities of 0:28:11.680 --> 0:28:16.000 daily living. Things like walking become very difficult and can 0:28:16.080 --> 0:28:20.119 result in frequent falls, which can be very dangerous. But 0:28:20.160 --> 0:28:24.400 even activities like getting out of bed, showering, getting dressed, 0:28:24.520 --> 0:28:27.320 all of these can become difficult because you don't have 0:28:27.560 --> 0:28:32.360 control over the movements of your muscles. And then dysphasia, 0:28:32.600 --> 0:28:36.639 so difficulty swallowing is particularly problematic because that can result 0:28:36.760 --> 0:28:40.640 in aspiration of food into the lungs, which can result 0:28:40.680 --> 0:28:46.360 in pneumonia. But Huntington's disease is not just a motor disorder, 0:28:46.760 --> 0:28:50.560 which is why the old name is no longer the name. 0:28:52.040 --> 0:28:58.240 Huntington's causes a range of neurocognitive, and psychiatric changes as well. 0:28:59.320 --> 0:29:03.120 So first, not first in terms of the course of disease, 0:29:03.200 --> 0:29:05.360 but just first of what I'm going to talk about 0:29:06.440 --> 0:29:09.920 is depression, which is far more common in people with 0:29:10.040 --> 0:29:13.840 Huntington's disease than in the general population, and I think 0:29:13.880 --> 0:29:16.680 what's important is that it might be easy if you 0:29:16.840 --> 0:29:20.400 just aren't thinking, to dismiss this as the result of 0:29:20.440 --> 0:29:24.800 being diagnosed with an incurable fatal disease. But it's not 0:29:25.600 --> 0:29:30.200 just that. Even though we don't fully understand depression in 0:29:30.280 --> 0:29:33.560 general and the effects of depression on the brain, or 0:29:34.080 --> 0:29:37.680 every single change that happens in Huntington's disease in the brain, 0:29:38.440 --> 0:29:41.040 we do have a lot of evidence that the effects 0:29:41.080 --> 0:29:44.040 of Huntington's on the structure of the brain itself is 0:29:44.080 --> 0:29:47.440 what makes people more at risk for depression and other 0:29:47.480 --> 0:29:52.680 psychiatric illnesses like anxiety, psychosis, menia, et cetera. 0:29:52.880 --> 0:29:55.720 It's like actual physical changes exactly right. 0:29:57.080 --> 0:30:01.120 And then the other hallmark of Huntington's disease is dementia, 0:30:01.360 --> 0:30:07.960 which is cognitive decline, so unlike Alzheimer's, so I think Parkinson's, 0:30:08.400 --> 0:30:12.080 Huntington's and Alzheimer's often get talked about in relation to 0:30:12.120 --> 0:30:17.360 each other for different reasons. But unlike Alzheimer's dementia, which 0:30:17.480 --> 0:30:23.360 tends to affect memory first, especially short term memory, the 0:30:23.600 --> 0:30:28.000 dementia and cognitive decline with Huntington's disease tends to affect 0:30:28.040 --> 0:30:32.000 what we call executive functions first, So that's things like 0:30:32.080 --> 0:30:37.240 decision making, planning, kind of like mental flexibility to new 0:30:37.320 --> 0:30:43.160 scenarios and reaction. And so this can result in behavioral changes, 0:30:43.880 --> 0:30:48.360 and this is something that friends and family can sometimes notice, 0:30:48.520 --> 0:30:52.960 even sometimes before a person experiencing these changes might notice anything, 0:30:54.040 --> 0:30:57.520 but they can be very subtle and often can happen 0:30:58.000 --> 0:31:02.120 before any of these motor side and can stay very 0:31:02.280 --> 0:31:06.200 mild for a long long time throughout the course of disease. Okay, 0:31:07.360 --> 0:31:11.120 And this is likely because the vasal ganglia is involved 0:31:11.560 --> 0:31:14.720 with a lot more than just motor coordination. So these 0:31:14.800 --> 0:31:18.760 kind of small changes and small amounts of neuronal death 0:31:18.960 --> 0:31:25.280 scattered throughout can result in these changes. And because Huntington's 0:31:25.320 --> 0:31:30.280 does eventually affect the entire brain, eventually memory becomes impaired 0:31:30.320 --> 0:31:30.760 as well. 0:31:31.440 --> 0:31:34.600 And so in terms of the progression, and like, first 0:31:34.640 --> 0:31:38.160 of all, how predictable is it? Are there you know 0:31:38.280 --> 0:31:40.800 stages that you know you could say, well, this is 0:31:41.040 --> 0:31:44.440 the typical stage, one stage, et cetera. And if it 0:31:44.480 --> 0:31:47.600 is predictable, why do we see, like why does that happen? 0:31:47.600 --> 0:31:49.360 Why does it progress in that order? 0:31:49.800 --> 0:31:55.120 Yeah, great question. There are stages in that there is 0:31:55.920 --> 0:32:00.600 pre symptomatic and then what we call clinical disease, which 0:32:00.640 --> 0:32:03.560 is after a person becomes symptomatic. And most of the 0:32:03.640 --> 0:32:09.560 time we consider symptomatic to be symptomatic with motor symptoms. Okay, 0:32:09.760 --> 0:32:12.280 But then a lot of times, you know, if you 0:32:13.120 --> 0:32:15.520 are talking with someone and you and they think about it, 0:32:15.520 --> 0:32:17.800 they're like, yeah, well, maybe I have noticed like a 0:32:17.840 --> 0:32:20.240 little bit of a personality change, or I was having 0:32:20.240 --> 0:32:23.400 difficulties at work before that, but they wouldn't have attributed 0:32:23.440 --> 0:32:26.640 it because they didn't know that they had Huntington's right 0:32:26.760 --> 0:32:31.840 until the motor symptoms happened. But to answer your question, no, 0:32:32.160 --> 0:32:36.520 there isn't a sequence to this, okay, and it can 0:32:36.560 --> 0:32:40.720 be very very variable from person to person, and the 0:32:40.800 --> 0:32:45.560 sequence does not depend on the number of repeats. So 0:32:46.360 --> 0:32:50.040 the vast majority of people with Huntington's disease will have 0:32:50.120 --> 0:32:56.160 onset sometime between their thirties and fifties, and everyone that 0:32:56.240 --> 0:32:59.120 has more than forty of these CAG repeats will have 0:32:59.200 --> 0:33:05.800 symptoms by age sixty five, pretty much. But while the 0:33:06.000 --> 0:33:10.120 length of repeats doesn't correlate to like what symptom is 0:33:10.120 --> 0:33:13.040 going to be first, or even how quickly the symptoms 0:33:13.040 --> 0:33:16.400 are going to progress, or anything like that. What it 0:33:16.480 --> 0:33:21.479 does correlate to is the early onset of symptoms. Right, 0:33:21.720 --> 0:33:26.800 So the longer this CAG repeat, the earlier you're likely 0:33:26.880 --> 0:33:29.400 to see symptoms onset. 0:33:29.720 --> 0:33:34.000 And then that happens in successive generations, right exactly. 0:33:34.280 --> 0:33:41.320 Yeah, so something called anticipation happens where because this microsatellite 0:33:41.400 --> 0:33:47.080 region is so unstable, which with each generation that length 0:33:47.200 --> 0:33:52.200 is likely to become longer. It doesn't necessarily, but essentially 0:33:52.240 --> 0:33:55.880 seventy five percent of the time when that cell replicates, 0:33:55.880 --> 0:33:59.600 when any cell replicates that has that unstable repeat, it 0:33:59.640 --> 0:34:03.960 will expand, and so that means that a child with 0:34:04.160 --> 0:34:08.399 a longer repeat could have earlier onset of disease. Once 0:34:08.400 --> 0:34:11.560 you get to above like sixty repeats, you can have 0:34:11.600 --> 0:34:15.640 what's actually called juvenile onset Huntington's, which happens if someone 0:34:15.680 --> 0:34:19.440 has symptoms before age twenty, and that does tend to 0:34:19.440 --> 0:34:22.360 look a little bit different than Huntington's that has a 0:34:22.440 --> 0:34:25.439 normal onset of thirty to fifty, where you have more 0:34:25.480 --> 0:34:28.880 of that slow rigid movement early on in the disease 0:34:29.160 --> 0:34:34.080 rather than the Korea form involuntary movement. But what is 0:34:35.400 --> 0:34:41.400 kind of universal is that once symptoms begin then this 0:34:41.520 --> 0:34:45.560 disease does progress, and it continues to progress. It is 0:34:45.880 --> 0:34:50.600 essentially universally fatal within about ten to thirty years of 0:34:50.680 --> 0:34:55.040 initial onset of symptoms. Most of the time, death is 0:34:55.080 --> 0:34:59.680 not from the disease itself, but from complications associated with 0:34:59.760 --> 0:35:04.320 fun or more commonly with pneumonia due to aspiration because 0:35:04.360 --> 0:35:06.440 of that, dysphasia and difficulty swallowing. 0:35:08.960 --> 0:35:13.560 So we talk about this as a genetic inheritable disease, 0:35:14.840 --> 0:35:18.320 But can it occur randomly? 0:35:19.080 --> 0:35:24.040 Yes, so it can certainly occur where there is no 0:35:24.160 --> 0:35:28.960 family history. And that's because if you have a CAG 0:35:29.239 --> 0:35:32.960 repeat length of anywhere from like twenty six to thirty 0:35:33.000 --> 0:35:36.920 five or twenty eight to thirty five, that is an 0:35:37.040 --> 0:35:41.200 unstable length. But you, yourself and anyone in your family 0:35:41.360 --> 0:35:47.720 wouldn't have disease from that. But that microsatellite could mutate 0:35:48.120 --> 0:35:51.120 in your eggs or your sperm, and then your children 0:35:51.200 --> 0:35:54.920 could have Huntington's disease. Gotcha, So we do see it 0:35:55.000 --> 0:35:59.160 happen absolutely. I think I think I read I should 0:35:59.200 --> 0:36:01.000 double check this number, but I think I read about 0:36:01.000 --> 0:36:06.520 eight percent of the time. Okay, yeah, so not super common, 0:36:06.680 --> 0:36:12.160 but absolutely possible. So that's the biology of Huntington's disease. 0:36:13.080 --> 0:36:16.640 I guess one question I didn't ask was why is 0:36:16.640 --> 0:36:18.160 it a later in life onset? 0:36:18.760 --> 0:36:21.719 Yeah, that's it's a good question. It's likely related to 0:36:22.120 --> 0:36:25.760 that it takes that much time for this abnormal protein 0:36:25.800 --> 0:36:29.719 to accumulate. So remember that, because this is an autosomal 0:36:29.800 --> 0:36:33.400 dominant disorder, you only need to have one copy of 0:36:33.440 --> 0:36:38.200 this gene. So how often is your cell copying making 0:36:38.280 --> 0:36:42.320 a protein based on that half based on that mutated 0:36:42.360 --> 0:36:45.680 gene versus based on your normal copy? So like, what's 0:36:45.719 --> 0:36:48.800 the ratio of normal Huntington in your cells to abnormal 0:36:48.880 --> 0:36:51.359 Huntington in your cells? And how long does it then 0:36:51.440 --> 0:36:54.560 take to accumulate this toxic protein. 0:36:55.880 --> 0:36:59.720 It's also interesting that there's not like a check system 0:37:00.120 --> 0:37:03.280 for abnormal proteins. 0:37:03.400 --> 0:37:07.279 So it's very interesting and it's something that people are 0:37:07.320 --> 0:37:10.200 working on in terms of treatment, Like can we change 0:37:10.280 --> 0:37:14.799 how cells process protein and deal with it so that 0:37:14.840 --> 0:37:18.880 we don't have this accumulation of these abnormal protein sheets? 0:37:18.960 --> 0:37:19.200 Right? 0:37:20.200 --> 0:37:20.600 Yeah. 0:37:20.640 --> 0:37:23.960 What I think is very interesting about the biology of 0:37:24.080 --> 0:37:27.759 Huntington's erin is that we know so much, Like I 0:37:27.800 --> 0:37:30.640 just gave you so much detail, right, like a lot 0:37:30.719 --> 0:37:35.799 of detail, and yet we also know so little at 0:37:35.800 --> 0:37:40.960 the same time. Yeah, yeah, And I think a lot 0:37:41.040 --> 0:37:43.319 of that too has to do with just that we 0:37:43.440 --> 0:37:46.240 know so little about our brain. You know, our brain 0:37:46.360 --> 0:37:52.520 is still Neurocognitive disorders in general are not well understood, 0:37:52.760 --> 0:37:57.680 the mechanisms, the specific nitty gritties of it, right, We 0:37:57.880 --> 0:37:59.120 just don't have the answers yet. 0:38:00.120 --> 0:38:04.640 That of course prohibits any like good treatments from being. 0:38:04.719 --> 0:38:10.120 Exactly developed quickly. So what I'm curious about, Aaron, is 0:38:11.120 --> 0:38:16.680 how we got to this point, Like, what is Huntington's 0:38:16.719 --> 0:38:22.040 like in history, because it's been around forever. This protein 0:38:22.120 --> 0:38:25.560 is in us, so yeah, so how did we get 0:38:25.600 --> 0:38:27.720 to this point? Yeah? 0:38:27.800 --> 0:38:32.040 I will try to answer this questions right after this break. 0:39:05.920 --> 0:39:09.719 In the June thirtieth, eighteen o six edition of the 0:39:09.760 --> 0:39:14.560 Suffolk Gazette, there's a brief news communication from East Hampton 0:39:15.040 --> 0:39:18.200 describing the tragic death of a woman named Phoebe Hedges, 0:39:18.920 --> 0:39:21.640 who was believed to have walked into the sea and 0:39:21.719 --> 0:39:22.520 not looked back. 0:39:23.960 --> 0:39:24.400 Quote. 0:39:24.520 --> 0:39:27.920 This extraordinary step is attributed to her extreme dread of 0:39:27.960 --> 0:39:31.280 the disorder called Saint Vidas's Dance, with which she began 0:39:31.360 --> 0:39:34.080 to be affected and which her mother now has to 0:39:34.160 --> 0:39:38.080 a great degree. This is one of the earliest reports 0:39:38.120 --> 0:39:42.719 of what would later be described as Huntington's disease. And 0:39:43.160 --> 0:39:45.719 I apologize for starting off in such a dark way, 0:39:46.200 --> 0:39:48.279 but I think that there's a lot that we can 0:39:48.360 --> 0:39:54.000 tell from this really short description in this newspaper. First, 0:39:54.080 --> 0:39:57.200 it shows us that Saint Vidas's dance still seemed to 0:39:57.239 --> 0:40:01.680 be widely known if you remember for our Dancing plague episode. 0:40:02.239 --> 0:40:06.000 I'm going to go over that like briefly again later. Anyway, 0:40:06.040 --> 0:40:09.480 The point is it was still widely known. Also that 0:40:09.560 --> 0:40:13.799 the disease can be extremely emotionally traumatic, especially due to 0:40:14.080 --> 0:40:18.600 its familial nature, like you talked about, Aaron, And also 0:40:18.719 --> 0:40:24.040 that the exclusion or stigmatization of families where Huntington's was 0:40:24.280 --> 0:40:28.520 known to occur wasn't the rule. That in some communities, 0:40:28.719 --> 0:40:33.799 like apparently in East Hampton, these families or individuals that 0:40:34.320 --> 0:40:38.480 had Huntington's were highly respected and very much integrated into 0:40:38.520 --> 0:40:40.239 and accommodated by the community. 0:40:41.320 --> 0:40:43.240 And I mentioned this last point. 0:40:42.880 --> 0:40:47.640 Because it serves as a sharp contrast for a good 0:40:47.800 --> 0:40:52.640 chunk of the social history of Huntington's and especially some 0:40:52.680 --> 0:40:57.000 of the prejudices that were created shortly after the disease 0:40:57.120 --> 0:41:02.560 was first described, and that persisted long after that. So 0:41:02.880 --> 0:41:08.160 let's begin. Most histories of Huntington's disease start off with 0:41:08.480 --> 0:41:11.480 the man for whom the disease is named, George Huntington. 0:41:12.120 --> 0:41:14.600 But I wanted to go back a little. 0:41:14.320 --> 0:41:16.759 Further than that. Of course you did, Eric. 0:41:16.840 --> 0:41:21.520 Of course, context context, context, in case you haven't listened 0:41:21.560 --> 0:41:23.960 to our Dancing plague episode, which I think it's a 0:41:23.960 --> 0:41:27.000 pretty fun episode, so I recommend it, right. 0:41:26.960 --> 0:41:27.680 Yeah, definitely. 0:41:28.280 --> 0:41:32.239 Essentially, what happened was that in fifteen eighteen there were 0:41:32.239 --> 0:41:35.120 also other small outbreaks, but the big one happened in 0:41:35.160 --> 0:41:40.120 fifteen eighteen in Strasburg. There was this outbreak of contagious 0:41:40.239 --> 0:41:45.759 and unstoppable dancing and side notes, fifteen eighteen happened to 0:41:45.800 --> 0:41:48.680 be the year after a big sweating sickness outbreak in 0:41:48.719 --> 0:41:49.240 the area. 0:41:49.480 --> 0:41:52.440 Ooh, it's all coming together, all. 0:41:52.280 --> 0:41:56.120 Coming together, okay. And so this dancing outbreak came to 0:41:56.160 --> 0:42:00.760 be called Saint Vitas's dance or Saint Vitas's Korea Korea 0:42:00.840 --> 0:42:05.719 from the Greek for dance like choreography, et cetera. Because 0:42:06.040 --> 0:42:08.520 people would go to the shrine of Saint Vidas to 0:42:08.520 --> 0:42:12.000 be cured and although the fifteen eighteen outbreak was the largest, 0:42:12.440 --> 0:42:14.400 it was not the only one, and there were smaller 0:42:14.440 --> 0:42:18.320 outbreaks in the following years. And by the eighteen hundreds 0:42:18.320 --> 0:42:22.880 these epidemics had stopped happening pretty much entirely, but the 0:42:23.040 --> 0:42:26.240 name of the condition or the condition itself didn't fade 0:42:26.320 --> 0:42:31.040 from public memory, because other people still experienced these similar 0:42:31.120 --> 0:42:35.400 movement disorders, like, for instance, Phoebe Hedges. So I just 0:42:35.480 --> 0:42:40.080 mentioned earlier, but what Phoebe was experiencing in eighteen o 0:42:40.280 --> 0:42:43.760 six was not an outbreak of dancing plague. Of course, 0:42:44.239 --> 0:42:46.360 there was just no other name for it at the time, 0:42:47.360 --> 0:42:52.160 and Saint Vitas's dance or just korea was a sort 0:42:52.160 --> 0:42:55.040 of catch all term for any kind of movement disorder 0:42:55.280 --> 0:42:58.920 at that time. Really only starting in the eighteen hundreds 0:42:58.960 --> 0:43:02.560 is when clinicians start paying closer attention to these Koreas, 0:43:03.160 --> 0:43:08.040 especially those that happened in children, possibly because of the 0:43:08.160 --> 0:43:13.879 rise in rheumatic fever due to like population growth, cities growth. 0:43:13.560 --> 0:43:14.040 Et cetera. 0:43:14.280 --> 0:43:16.600 Yeah, and so when. 0:43:16.480 --> 0:43:20.480 Physicians started describing these cases, they may have also noticed 0:43:20.520 --> 0:43:23.759 another kind of Korea, one that was different from this 0:43:23.880 --> 0:43:28.879 childhood or Sydenham's Korea. By the time that George Huntington's 0:43:28.920 --> 0:43:32.000 description of the disease was published in eighteen seventy two, 0:43:33.040 --> 0:43:36.040 there were at least five other previous descriptions of the 0:43:36.040 --> 0:43:41.600 disease going back to the eighteen forties. But we call 0:43:41.640 --> 0:43:45.600 it Huntington's, not Water's disease or LUN's disease. 0:43:45.960 --> 0:43:46.200 Why. 0:43:47.080 --> 0:43:51.240 Yeah, Well, it might just be a matter of timing, invisibility, 0:43:51.280 --> 0:43:55.919 and chance. But another thing that made Huntington stand out 0:43:56.440 --> 0:44:01.440 was his description, which the famous doctor William Ostler said, quote, 0:44:01.880 --> 0:44:04.719 there are few instances in the history of medicine in 0:44:04.760 --> 0:44:08.400 which a disease has been more accurately, more graphically, or 0:44:08.480 --> 0:44:09.719 more briefly described. 0:44:10.040 --> 0:44:14.000 Huh So it was just like a very very good description. 0:44:14.600 --> 0:44:14.960 Yeah. 0:44:15.040 --> 0:44:16.839 So he won the best Description award. 0:44:16.920 --> 0:44:20.040 He won the Best Description award. Okay, And at the 0:44:20.080 --> 0:44:23.960 tail end of Huntington's publication, which largely focused on other 0:44:24.080 --> 0:44:28.600 forms of Korea, Huntington added a few paragraphs on what 0:44:28.680 --> 0:44:34.319 he called hereditary Korea, noting its inherited nature, particularly that 0:44:34.360 --> 0:44:38.560 it didn't skip a generation mental decline as a common occurrence, 0:44:39.280 --> 0:44:43.880 and it's typically adult onset. It was descriptive yet to 0:44:43.960 --> 0:44:47.000 the point and in the decade after it was published, 0:44:47.040 --> 0:44:50.200 the disease that would later be called Huntington's Korea for 0:44:50.239 --> 0:44:54.000 this amazing description would get a whole lot more researchers 0:44:54.080 --> 0:45:00.080 interested in it, and not always for good reason. But 0:45:00.120 --> 0:45:02.360 before we get to that, I want to talk a 0:45:02.400 --> 0:45:05.520 bit about why the disease might have only been described 0:45:05.520 --> 0:45:08.759 in the late eighteen hundreds, which seems kind of late 0:45:08.800 --> 0:45:13.480 to me. Yeah, Like, you know, Saint Vidas's Dance had 0:45:13.520 --> 0:45:15.360 been around for a long time. 0:45:15.239 --> 0:45:16.640 Three hundred years between. 0:45:16.840 --> 0:45:19.680 Yeah, yeah, and so it might just be that, like 0:45:20.280 --> 0:45:23.480 there are accounts that people can't distinguish between Saint Vidas's 0:45:23.560 --> 0:45:27.240 dance and what might have been Huntington's. I'm not sure, 0:45:27.320 --> 0:45:32.239 but one of the things that people have suggested is 0:45:32.280 --> 0:45:36.640 that low life expectancy may have contributed to the apparent 0:45:36.920 --> 0:45:40.799 invisibility of the disease. Yeah, so people were more likely 0:45:40.840 --> 0:45:45.279 to die of something else before developing any symptoms that sense, 0:45:45.280 --> 0:45:47.680 which would yeah, which would also then sort of like 0:45:47.760 --> 0:45:53.719 obscure the inheritability aspect of it. But having said that, 0:45:53.800 --> 0:45:56.360 it's not like the eighteen hundreds, Like, it's not like 0:45:56.400 --> 0:45:59.200 the year from like seventeen ninety nine to eighteen hundred 0:45:59.239 --> 0:46:00.799 came with this huge, huge boost. 0:46:00.560 --> 0:46:01.760 In life expectancy. 0:46:02.920 --> 0:46:05.919 For example, if you were born in sixteen oh one, 0:46:06.320 --> 0:46:10.880 your life expectancy was thirty eight years. Oh no, whereas 0:46:10.880 --> 0:46:14.160 if you were born in eighteen thirty one, life expectancy 0:46:14.239 --> 0:46:18.200 was forty one years. Like from birth. And there are 0:46:18.280 --> 0:46:22.800 problems with life expectancy from birth because child because infant 0:46:22.800 --> 0:46:26.799 mortality was so high, et cetera. But anyway, so other 0:46:26.960 --> 0:46:29.960 people argue that it actually wasn't the slight increase in 0:46:30.000 --> 0:46:34.879 life expectancy, but rather the reframing of heredity overall and 0:46:34.920 --> 0:46:37.280 how we thought about the inheritance of traits. 0:46:37.680 --> 0:46:37.759 What. 0:46:38.960 --> 0:46:43.799 Yeah, So there was this boom around this time in 0:46:43.920 --> 0:46:48.680 natural history research and experimentation and livestock in plant breeding 0:46:49.120 --> 0:46:52.280 that had led to people thinking critically and publishing widely 0:46:52.400 --> 0:46:54.320 about the inheritability. 0:46:53.600 --> 0:46:57.000 Of traits like Mendel. 0:46:56.000 --> 0:47:01.160 Like Mendel, like Darwin, like if you remember back to 0:47:01.160 --> 0:47:03.719 our Prions episode, like all of the people who were 0:47:03.719 --> 0:47:05.919 doing sheep breeding at that time to try to find 0:47:05.920 --> 0:47:07.160 the best merino wool. 0:47:07.640 --> 0:47:08.279 Yeah. 0:47:08.320 --> 0:47:12.040 And also in medicine, there was still no germ theory 0:47:12.320 --> 0:47:16.719 in the early eighteen hundreds, and so heredity joined miasma 0:47:17.320 --> 0:47:21.040 as this way to explain why certain diseases occurred. Right, 0:47:21.760 --> 0:47:25.640 So there's that, and finally there's the matter of George 0:47:25.680 --> 0:47:28.560 Huntington and East Hampton. So the man and the place. 0:47:29.440 --> 0:47:33.600 George's grandfather, Abel, who was also a doctor, moved to 0:47:34.160 --> 0:47:37.000 this area of Long Island, New York in the late 0:47:37.040 --> 0:47:41.000 seventeen hundreds, where he set up a medical practice, and 0:47:41.120 --> 0:47:44.080 shortly after he arrived he learned of a few families 0:47:44.080 --> 0:47:47.160 in the area who were affected by something that people 0:47:47.360 --> 0:47:48.680 generally referred to. 0:47:48.680 --> 0:47:50.680 As quote that disease. 0:47:51.200 --> 0:47:55.480 Oh, the people who had that disease and their unaffected 0:47:55.480 --> 0:47:59.920 family members were not shunned or stigmatized. They held public office, 0:48:00.160 --> 0:48:03.319 they seemed to be supported by their families and by 0:48:03.320 --> 0:48:05.319 the rest of the community. It was just sort of 0:48:05.360 --> 0:48:07.520 like the way it is. It was like, this is 0:48:07.560 --> 0:48:11.440 how we are here. And George's father also became a 0:48:11.480 --> 0:48:15.040 doctor and some of his patients were also people with 0:48:15.760 --> 0:48:19.560 what would later be called Huntington's disease, and sometimes George 0:48:19.600 --> 0:48:23.239 would go on rounds with his dad. And so when 0:48:23.280 --> 0:48:26.719 George finished medical training, he not only was equipped with 0:48:26.800 --> 0:48:31.279 the ability to observe and describe certain conditions, he had 0:48:31.360 --> 0:48:35.799 the generational knowledge of his father and grandfather, and he 0:48:35.960 --> 0:48:38.239 also happened to live in a town which had a 0:48:38.320 --> 0:48:42.839 higher prevalence than in surrounding areas, and so this set 0:48:42.880 --> 0:48:46.319 him up to write his on Korea in eighteen seventy two. 0:48:47.560 --> 0:48:52.200 It was the only article he ever published apparently wow yeah. 0:48:52.480 --> 0:48:55.800 When his paper came out, other reports of Huntington started 0:48:55.800 --> 0:49:01.920 to trickle in, and not just from the US, Germany, France, Italy, Britain, Austria, Cuba, Poland, 0:49:01.960 --> 0:49:06.920 Russia and many other places reported case descriptions of what 0:49:07.080 --> 0:49:10.680 had started in eighteen eighty seven to be called Huntington's Korea. 0:49:11.719 --> 0:49:14.200 And this research on the late eighteen hundreds filled in 0:49:14.239 --> 0:49:18.279 the details of the clinical picture that Huntington had painted. So, 0:49:18.480 --> 0:49:22.840 for instance, insanity was mentioned as a defining feature in 0:49:22.880 --> 0:49:27.680 George Huntington's description of the disease, but later physicians noted 0:49:27.920 --> 0:49:31.200 that the mental impairment due to the disorder was not 0:49:31.360 --> 0:49:34.600 always severe, or it was variable or at onset differently, 0:49:35.239 --> 0:49:40.880 And it was essentially their understanding of how cognitive function 0:49:41.320 --> 0:49:42.800 worked became more nuanced. 0:49:42.920 --> 0:49:44.160 Yeah yeah. 0:49:44.360 --> 0:49:48.560 And then the average age of onset was studied, autopsies 0:49:48.600 --> 0:49:51.759 were performed, on people who had died from Huntington's and 0:49:52.360 --> 0:49:56.839 these showed these physical changes in the brain, and there 0:49:56.920 --> 0:49:59.239 was a whole lot of compare and contrast with the 0:49:59.520 --> 0:50:02.360 other highly studied form of Korea from this time, so 0:50:02.480 --> 0:50:08.160 Sydenham's Korea. William Osler, who was super interested in all 0:50:08.160 --> 0:50:11.319 types of Korea, got in touch with Huntington to ask 0:50:11.360 --> 0:50:13.799 whether he could arrange a meeting with some people who 0:50:13.800 --> 0:50:18.279 were affected by the disease in the town, and Huntington said, no, 0:50:18.560 --> 0:50:20.239 I don't think that's a good idea. I want to 0:50:20.239 --> 0:50:23.800 respect these people of privacy and you shouldn't bother them. Wow, 0:50:24.080 --> 0:50:27.880 which like in the late eighteen hundreds, I'm shocked. 0:50:27.560 --> 0:50:31.120 By I'm totally shocked, but I know way to go. Yeah, 0:50:31.440 --> 0:50:33.840 I'm guessing Fossler didn't listen. 0:50:34.680 --> 0:50:38.160 Actually he did. Yeah, he was like okay. And then 0:50:38.280 --> 0:50:41.680 Huntington moved away to a different town and another doctor 0:50:41.719 --> 0:50:45.440 took over the practice, and Ostler asked him, and at 0:50:45.480 --> 0:50:48.840 first this new doctor Osbourne said the same thing that 0:50:48.960 --> 0:50:52.000 Huntington had said, No, it's best if you don't come here. 0:50:53.520 --> 0:50:56.640 But then he changed his mind, and it seems that 0:50:56.800 --> 0:51:00.719 he thought that maybe by having Ostler come there to 0:51:00.800 --> 0:51:03.960 do more research on the disease. It could increase awareness 0:51:04.040 --> 0:51:07.799 that could lead to more support and medical treatment and cures, 0:51:08.840 --> 0:51:12.080 But on the other hand, it could bring increased scrutiny 0:51:12.120 --> 0:51:16.600 and unwanted attention to these people without their consent. Osler 0:51:16.719 --> 0:51:20.160 never did end up visiting East Hampton. He did conduct 0:51:20.160 --> 0:51:24.320 research on Huntington's disease on other families and other places. 0:51:25.360 --> 0:51:29.040 But in the last few years of the nineteenth century 0:51:29.160 --> 0:51:33.440 and in the first several decades of the twentieth, Huntington's 0:51:33.640 --> 0:51:38.360 and Osborne's initial fears were realized as the focus on 0:51:38.440 --> 0:51:42.319 Huntington's turned to one of the defining characteristics of the 0:51:42.360 --> 0:51:48.440 disease its heritability. So, like I mentioned, general patterns of 0:51:48.480 --> 0:51:51.560 inheritance had been figured out for a while by the 0:51:51.680 --> 0:51:55.320 end of the eighteen hundreds, thanks to livestock breeders, who 0:51:55.960 --> 0:52:00.040 really could be considered like the first geneticists, even more so, 0:52:00.120 --> 0:52:03.560 I would argue than Mendel. By the time Mendel was 0:52:03.600 --> 0:52:06.160 playing with his p's in the eighteen sixties, these breeders 0:52:06.239 --> 0:52:09.600 already knew about dominant and recessive forms of inheritance. Like 0:52:09.680 --> 0:52:13.560 maybe not in that formal language, but they were incredibly knowledgeable. 0:52:14.680 --> 0:52:18.960 But interest in the field of heritability grew throughout the 0:52:19.000 --> 0:52:22.680 late eighteen hundreds and into the nineteen hundreds, especially when 0:52:22.719 --> 0:52:26.359 Mendel's work, which was published in eighteen sixty six but 0:52:26.800 --> 0:52:29.759 was sort of like lost, like no one talked about it, 0:52:29.800 --> 0:52:33.319 and it was rediscovered in like nineteen hundred. Yeah, and 0:52:33.400 --> 0:52:37.600 Mendel's work gave this like form and calculation and structure 0:52:37.640 --> 0:52:41.920 to these patterns, and the interest grew even more broadly 0:52:42.320 --> 0:52:46.520 beyond that. It wasn't just plant or livestock breeders or 0:52:46.600 --> 0:52:50.080 natural historians that had an interest in which traits were 0:52:50.120 --> 0:52:55.759 passed down, but also so called social thinkers quote unquote 0:52:56.160 --> 0:52:59.480 who began to take these biological concepts and apply them 0:52:59.520 --> 0:53:04.080 to what they saw as social problems. So begins the 0:53:04.120 --> 0:53:07.839 story of eugenics. And this is a story that I've 0:53:07.880 --> 0:53:11.520 touched on so many times in this podcast. If you 0:53:11.560 --> 0:53:14.120 remember back in any of the episodes where I talk 0:53:14.120 --> 0:53:18.600 about eugenics, especially I think the birth control episode, you 0:53:18.640 --> 0:53:21.960 may remember how the term race suicide quote unquote really 0:53:22.080 --> 0:53:25.240 gained traction in the early twentieth century in the US. 0:53:25.480 --> 0:53:29.800 It was one of Teddy Roosevelt's favorite terms. Basically white 0:53:30.000 --> 0:53:33.880 middle class Americans began to be fearful of the influx 0:53:33.920 --> 0:53:36.520 of immigrants, the growth of the lower class, their own 0:53:36.560 --> 0:53:37.560 declining birth. 0:53:37.400 --> 0:53:38.000 Rate, etc. 0:53:38.840 --> 0:53:41.400 Essentially, they were worried that they were going to become 0:53:41.480 --> 0:53:44.959 outnumbered by those they deemed to be unfit or less. 0:53:45.000 --> 0:53:49.720 Then the word degeneration itself began to take on multiple meanings. 0:53:50.000 --> 0:53:52.600 It could be used medically to describe how someone's ability 0:53:52.640 --> 0:53:56.799 to walk and talk and function normally slowly deteriorated, and 0:53:56.840 --> 0:53:59.760 to the eugenesis, it could be used to vaguely describe 0:53:59.800 --> 0:54:03.600 the gradual decline of society whatever that meant. However, they 0:54:03.640 --> 0:54:07.479 wanted it to mean eugenics, and this concept of race 0:54:07.520 --> 0:54:11.799 suicide focused particularly on who was procreating and how to 0:54:11.800 --> 0:54:15.680 control it. They wanted to encourage certain people to procreate 0:54:15.760 --> 0:54:20.040 more and prevent others from procreating at all, by force 0:54:20.120 --> 0:54:23.720 if necessary. The first few decades of the twentieth century 0:54:23.880 --> 0:54:27.400 saw the rise of eugenics from this like niche theoretical 0:54:27.480 --> 0:54:33.320 biology concept to a widespread public movement, with state laws 0:54:33.440 --> 0:54:37.799 legitimizing this way of thinking and genetic research providing a 0:54:37.840 --> 0:54:45.400 scientific basis for it. Marriage prohibition, involuntary sterilization, racist immigration laws, those. 0:54:45.160 --> 0:54:47.000 Were all like the order of the day. 0:54:48.120 --> 0:54:51.920 And I think I'm probably repeating myself from past episodes 0:54:51.920 --> 0:54:54.960 when I say that Hitler and the Nazi Party got 0:54:55.080 --> 0:54:59.040 many of their ideas from directly from the eugenics movement 0:54:59.120 --> 0:55:04.239 in the United States. It's hard to overstate how just 0:55:04.320 --> 0:55:08.480 how pervasive eugenics became and in some ways. 0:55:08.360 --> 0:55:09.360 Still is today. 0:55:10.360 --> 0:55:15.239 Anyway, as eugenics gained traction, it began to hone in 0:55:15.280 --> 0:55:18.880 on certain groups of people or individual traits or conditions 0:55:18.880 --> 0:55:22.799 that they felt were quote unfit. One of these was 0:55:22.960 --> 0:55:27.400 Huntington's disease. Huntington's disease was actually one of the first 0:55:27.400 --> 0:55:31.120 genetic diseases to be described as dominant by William Bateson 0:55:31.280 --> 0:55:34.880 and Reginald Punnett of Like Punnett Square fame who in 0:55:35.000 --> 0:55:38.359 nineteen oh seven. And you know, this is something that 0:55:38.480 --> 0:55:40.760 like I think I have to relearn every so often. 0:55:40.880 --> 0:55:44.000 But just as the twentieth century birth control movement in 0:55:44.040 --> 0:55:47.200 the US has its roots in eugenics, so does the 0:55:47.200 --> 0:55:48.160 study of genetics. 0:55:48.560 --> 0:55:51.120 Yeah, I always have to relearn that as well. 0:55:51.280 --> 0:55:55.640 If someone was a geneticist in the early nineteen hundreds, 0:55:55.719 --> 0:56:02.080 they were very likely also eugenicist. Since George Huntington first 0:56:02.080 --> 0:56:05.239 described the condition in eighteen seventy two, there had been 0:56:05.280 --> 0:56:09.480 no substantial developments in terms of treatment of the disease, 0:56:10.080 --> 0:56:16.280 and because of this, eugenesis then increasingly turned towards emphasizing prevention, 0:56:17.000 --> 0:56:23.360 either through sterilization, restricting immigration, or outlawing marriage. Enter Charles Davenport. 0:56:24.560 --> 0:56:27.960 Charles Davenport may not have started the eugenics movement in 0:56:28.000 --> 0:56:31.319 the US, but he was friends with Francis Galton, who 0:56:31.400 --> 0:56:35.319 was the father of eugenics, and he also founded the 0:56:35.840 --> 0:56:41.480 Eugenics Record Office in nineteen ten, where field workers and 0:56:41.560 --> 0:56:45.320 scientists were trained in how to collect and analyze data 0:56:45.440 --> 0:56:51.280 to push their eugenic propaganda. Osborne's fears about the increased 0:56:51.280 --> 0:56:56.040 attention to the residence of Easthampton and elsewhere with Huntington's 0:56:56.040 --> 0:57:01.040 disease were about to come true. After read about the 0:57:01.040 --> 0:57:05.160 genetic basis of Huntington's and its patterns of inheritance, he 0:57:05.239 --> 0:57:08.240 viewed it as a perfect subject for a large scale 0:57:08.239 --> 0:57:11.600 project in which he would identify the source of the 0:57:11.600 --> 0:57:14.439 disease in the US, as well as shed more light 0:57:14.640 --> 0:57:19.160 generally on heritable disease. The person responsible for carrying out 0:57:19.240 --> 0:57:22.200 much of this study was the eugenics field worker, which, 0:57:22.320 --> 0:57:25.960 like I can't believe is an actual phrase a job 0:57:26.040 --> 0:57:33.440 title eugenics field worker in the nineteen hundreds, Yes, yeah, 0:57:33.560 --> 0:57:38.200 named Elizabeth Munsey. Munsey would go around to towns in 0:57:38.240 --> 0:57:41.959 different states where families with Huntington's had been identified, both 0:57:42.000 --> 0:57:46.840 to interview them as well as constructive family tree Over 0:57:46.920 --> 0:57:49.920 her years as a field worker, she created pedigrees with 0:57:50.000 --> 0:57:54.080 over five thousand people and identified nearly one thousand people 0:57:54.160 --> 0:57:57.080 with Huntington's, about two hundred and fifty of which were 0:57:57.120 --> 0:58:00.720 still living at the time of her survey. And while 0:58:00.720 --> 0:58:03.520 I was reading about this, I just could not stop 0:58:03.560 --> 0:58:07.400 thinking about how horrifying it is that there was a 0:58:07.440 --> 0:58:12.040 eugenics records office collecting the names and locations of people 0:58:12.160 --> 0:58:16.720 with certain diseases. And we can get a taste as 0:58:16.880 --> 0:58:19.920 to what could have happened with this info in the 0:58:20.080 --> 0:58:24.240 US hypothetically by looking at what did happen in Germany 0:58:25.200 --> 0:58:27.480 in the years leading up to World War Two. People 0:58:27.520 --> 0:58:31.120 with Huntington's were among the hundreds of thousands of people 0:58:31.240 --> 0:58:34.760 forcibly sterilized in Germany. Of the three hundred and fifty 0:58:34.840 --> 0:58:38.560 thousand to four hundred thousand people sterilized in Germany during 0:58:38.640 --> 0:58:42.280 nineteen thirty three to nineteen thirty nine. Around three thousand 0:58:42.280 --> 0:58:45.320 to thirty five hundred of those people were people that 0:58:45.360 --> 0:58:50.560 had Huntingtons. And then when the war started, so did 0:58:50.680 --> 0:58:54.200 the exterminations. And we don't really have good numbers for 0:58:54.280 --> 0:58:58.440 that with regards to people with Huntingtons. Anyway, back to 0:58:58.520 --> 0:58:59.080 Munsey and. 0:58:59.040 --> 0:58:59.720 Her field work. 0:59:01.240 --> 0:59:07.080 Rather inconveniently for Charles Davenport, who held these prejudicial views 0:59:07.120 --> 0:59:10.080 that people with diseases of any kind were degenerate or 0:59:10.200 --> 0:59:14.920 feewal minded, Munsey actually gained a great deal of admiration 0:59:15.160 --> 0:59:17.640 and respect for many of the people that she interviewed. 0:59:18.080 --> 0:59:21.240 I mean, she was still eugenicist, let's not forget that. Yeah, 0:59:21.280 --> 0:59:23.120 But what she found was that there was no hard 0:59:23.160 --> 0:59:25.800 and fast rule as to who developed Korea and who 0:59:25.800 --> 0:59:30.000 didn't in terms of like, oh, this person is a scoundrel. 0:59:30.080 --> 0:59:34.440 Oh this person is like really well respected in the community. 0:59:34.000 --> 0:59:36.840 Like nothing to do with who you are or what 0:59:36.920 --> 0:59:39.600 you do for a job or anything like that. 0:59:40.000 --> 0:59:45.400 Yeah, And this went against the prevailing thought of the day, 0:59:45.640 --> 0:59:49.680 at least for the eugenicist that the disease was specific 0:59:49.760 --> 0:59:53.600 to lower classes, and that was a notion that persisted 0:59:53.600 --> 0:59:58.040 well into the nineteen sixties. In terms of Huntington's Charles 0:59:58.080 --> 1:00:00.960 Davenport and Elizabeth Munsey publish the data that months he 1:00:01.040 --> 1:00:05.000 collected in nineteen sixteen in the get this This is 1:00:05.040 --> 1:00:13.560 an actual journal, American Journal of Insanity. What, yes, I 1:00:13.560 --> 1:00:16.080 wonder when it stopped being a journal or what it 1:00:16.120 --> 1:00:16.640 turned into. 1:00:16.840 --> 1:00:19.360 I know it's gonna you probably just turned into something. 1:00:19.680 --> 1:00:23.600 Can we keep googling it? 1:00:23.600 --> 1:00:28.280 It lasted until nineteen twenty one, I think, Oh, American 1:00:28.360 --> 1:00:30.840 Journal of Psychiatry. I'm pretty sure. 1:00:33.080 --> 1:00:33.320 Yeah. 1:00:34.440 --> 1:00:38.960 So what they showed in this article was a much 1:00:39.000 --> 1:00:41.520 more varied picture than the one that George Huntington had 1:00:41.560 --> 1:00:46.000 painted a nearly forty years prior. In it, they discussed 1:00:46.000 --> 1:00:49.440 the variability of the disease, both in symptoms, severity, and 1:00:49.480 --> 1:00:54.360 age of onset in general. Though the paper was terrible statistically, 1:00:55.240 --> 1:00:58.360 and broad claims were made about the unfitness of these 1:00:58.400 --> 1:01:01.080 families and the bad care characters at the top of 1:01:01.120 --> 1:01:04.400 the family tree, this article was essentially used as this 1:01:04.560 --> 1:01:08.680 platform for his eugenic propaganda, and this way of thinking 1:01:08.720 --> 1:01:13.680 about Huntington's didn't die out with Davenport. Unfortunately, if anything, 1:01:14.200 --> 1:01:19.000 this article and that research quote unquote research added fuel 1:01:19.080 --> 1:01:23.160 to the fire. Based in part on Davenport and Munsey's publication, 1:01:23.560 --> 1:01:28.160 there's a Connecticut psychiatrist named Percy Vesi who created an 1:01:28.200 --> 1:01:32.120 origin story of Huntington's in the US as one in 1:01:32.160 --> 1:01:36.800 which witchcraft and scoundrels featured prominently from the very beginning. 1:01:37.240 --> 1:01:40.480 Come on, I mean this account was based on like 1:01:41.000 --> 1:01:44.760 horrible research and just an absence of facts. Everyone in 1:01:44.800 --> 1:01:48.640 his story was either described as a criminal or a 1:01:48.640 --> 1:01:51.320 low life of some kind, and he smeared the name 1:01:51.360 --> 1:01:55.200 of every person he listed. He then blamed Huntington's disease 1:01:55.280 --> 1:01:58.960 for their behavior, and in nineteen thirty two he used 1:01:58.960 --> 1:02:05.160 this article to sterilization His fiction of witchcraft and criminality 1:02:05.200 --> 1:02:12.280 associated with the disease was thoroughly, entirely, completely disproven, but 1:02:13.320 --> 1:02:14.880 only in the nineteen sixties. 1:02:15.720 --> 1:02:16.240 Wow. 1:02:16.600 --> 1:02:19.600 Yeah, so it was repeated and repeated and repeated, and 1:02:19.640 --> 1:02:22.520 still I saw it in some papers from like the eighties. 1:02:23.080 --> 1:02:27.640 Oh no, yeah, This story, which also I will note, 1:02:27.680 --> 1:02:31.400 has been reclaimed by some people with Huntington's as a 1:02:31.400 --> 1:02:34.000 way to sort of like show the enormous prejudice and 1:02:34.120 --> 1:02:38.040 exclusion and faced by people with the disease, and the 1:02:38.080 --> 1:02:42.680 difficulties in overcoming that. But this story created this set 1:02:42.720 --> 1:02:47.800 of stigmatizing associations that persisted in Huntington's literature for decades. 1:02:48.760 --> 1:02:52.000 I was shocked, but also not shocked to find out 1:02:52.040 --> 1:02:55.680 that in nineteen fifty one, there was an article published 1:02:55.800 --> 1:02:59.960 in the Journal of Science, like this extremely prestigious journal, 1:03:00.800 --> 1:03:04.200 in which the authors claimed that there was enormously higher 1:03:04.240 --> 1:03:08.240 fertility in men with Huntington's compared to their siblings that did. 1:03:08.120 --> 1:03:09.320 Not have the disease. 1:03:10.600 --> 1:03:14.520 They used a sample size of two two brothers. That's it, 1:03:15.560 --> 1:03:21.680 nineteen fifty one Science Vacine. These claims were refuted eight 1:03:21.760 --> 1:03:23.320 years later, eight. 1:03:23.240 --> 1:03:25.440 Years later, eight years. 1:03:25.280 --> 1:03:30.360 Yeah, after World War Two, the US's infatuation with eugenics 1:03:30.400 --> 1:03:34.280 was mostly over, and research on Huntington's turned towards treatment 1:03:34.320 --> 1:03:38.200 and molecular diagnosis. And I just want to say that 1:03:38.640 --> 1:03:41.520 I feel like I spent a lot of time on eugenics, 1:03:41.560 --> 1:03:43.640 and I do all the time in these episodes. 1:03:43.760 --> 1:03:46.680 Yeah, it's like every other episode I think these days 1:03:47.200 --> 1:03:48.200 think about it. 1:03:48.200 --> 1:03:52.520 It's a horrible and depressing topic, but I feel like 1:03:52.680 --> 1:03:57.240 it's not talked enough about in history or biology classes, 1:03:57.520 --> 1:03:59.240 at least in the ones that I took. Maybe that's 1:03:59.280 --> 1:04:03.360 different now, but I think it's really important to remember 1:04:03.480 --> 1:04:07.080 how people can misuse or misquote or straight up makeup 1:04:07.120 --> 1:04:11.320 information to push their own propaganda. By couching something in 1:04:11.400 --> 1:04:15.600 science or scientific language, you can really like cause a 1:04:15.640 --> 1:04:19.200 lot of harm if your claims are not supported or 1:04:19.240 --> 1:04:23.000 if you're pushing some sort of propaganda. And I think 1:04:23.040 --> 1:04:25.400 in the US we have this tendency to ignore the 1:04:25.480 --> 1:04:27.760 dark part of our history and pretend like we were 1:04:27.800 --> 1:04:30.600 the heroes, we were the saviors in like all of 1:04:30.640 --> 1:04:36.600 our stories. We have to acknowledge our past, our dark past. 1:04:36.400 --> 1:04:37.760 So that we can be better. 1:04:38.120 --> 1:04:40.920 Yeah, it just it has to happen. I think also 1:04:40.960 --> 1:04:43.680 a lot of the response that some people have about 1:04:43.880 --> 1:04:46.440 you know, eugenics is like, oh, well it was another time. 1:04:47.080 --> 1:04:49.040 It was you have to understand it in the context 1:04:49.080 --> 1:04:52.400 of that time. And it's like you can both understand 1:04:53.200 --> 1:04:55.919 why eugenics became popular in the context of the time 1:04:56.040 --> 1:04:58.840 and also be horrified that it became popular and. 1:04:58.800 --> 1:04:59.960 That state laws existed. 1:05:00.200 --> 1:05:02.320 Yeah, like those two things are not mutually exclusive. 1:05:02.560 --> 1:05:05.000 Not in fact, they are both true. 1:05:05.240 --> 1:05:08.440 Right, It's just like this happened to people. This actually 1:05:08.520 --> 1:05:10.320 did happen to people. How do we not have this 1:05:10.360 --> 1:05:15.520 happen again? Yeah, let's just be better. Let's try anyway, 1:05:16.240 --> 1:05:20.880 speaking of better and better things. Along with the renewed 1:05:20.920 --> 1:05:25.240 scientific interest in Huntington's, there was also the birth of 1:05:25.360 --> 1:05:29.800 several advocacy and support programs. The first was the Committee 1:05:29.800 --> 1:05:34.080 to Combat Huntington's Disease, now called the Huntington's Disease Society 1:05:34.080 --> 1:05:38.640 of America, founded by Marjorie Guthrie in nineteen sixty seven, 1:05:39.480 --> 1:05:43.080 the same year that her husband. And this is what 1:05:43.160 --> 1:05:45.560 cracks me up, Aaron, because every time I said this 1:05:45.680 --> 1:05:47.480 to you, you were like, I don't know who that is. 1:05:47.760 --> 1:05:50.200 I don't know who that is. I so I feel 1:05:50.200 --> 1:05:53.600 like you were talking about him in a completely different 1:05:53.640 --> 1:05:55.480 context recently, And I was like, Yeah, I don't know 1:05:55.520 --> 1:05:57.520 who that is. And I didn't even realize that it 1:05:57.600 --> 1:06:02.160 was Huntington's Yeah, Diddy Guthrie, Yeah, Woody Guthrie. I didn't 1:06:02.160 --> 1:06:04.680 know who that was. And then when I saw his 1:06:04.800 --> 1:06:07.720 name on the Wikipedia page, I was like, oh, I 1:06:07.760 --> 1:06:11.960 know that Aaron keeps talking about I thought you were 1:06:11.960 --> 1:06:14.560 just talking about him for other random reason. He has. 1:06:14.800 --> 1:06:16.040 He's like music. 1:06:15.840 --> 1:06:19.440 Rights, he's like music. 1:06:19.640 --> 1:06:27.920 Yeah. Woody Guthrie was an incredibly influential folk singer songwriter, 1:06:28.120 --> 1:06:31.560 so he inspired like the whole you know, folk music generation. 1:06:32.080 --> 1:06:35.160 He wrote this land is Your Land, for instance. I 1:06:35.240 --> 1:06:37.560 know that song a lot of other songs that you 1:06:37.600 --> 1:06:44.000 would recognize. His guitar said, this machine kills fascists, which 1:06:44.040 --> 1:06:47.000 is also another thing. I was thinking for a quarantine name. Ooh, 1:06:47.240 --> 1:06:51.840 that would be good anyway. So Woody Guthrie started to 1:06:51.880 --> 1:06:56.560 develop symptoms of Huntington's in like the nineteen forties and 1:06:56.640 --> 1:07:01.880 finally was diagnosed in nineteen fifty two. And Marjorie when 1:07:01.880 --> 1:07:05.720 he got his diagnosis, she was asking the doctors all 1:07:05.720 --> 1:07:09.280 these questions and the doctors were just like, well, that's it, sorry, 1:07:09.360 --> 1:07:11.600 Like there's nothing we can do. There's no advice I 1:07:11.600 --> 1:07:15.440 can give you. That's it. And she was like this, no, this, 1:07:15.600 --> 1:07:19.080 I'm not going to accept that, Like this isn't it, Like, 1:07:20.080 --> 1:07:22.560 you know, I want to talk to other people who've 1:07:22.600 --> 1:07:25.480 experienced this. I want to bring us all together so 1:07:25.560 --> 1:07:27.600 that we can get support, so we can get advice, 1:07:27.680 --> 1:07:31.360 so we can raise awareness, to get more information about 1:07:31.360 --> 1:07:34.640 this disease. And so in nineteen sixty seven, which was 1:07:34.680 --> 1:07:37.640 the same year that Woody Guthrie died of the disease. 1:07:38.440 --> 1:07:42.840 She founded this organization where other people could find information 1:07:43.040 --> 1:07:48.120 and get support, and this organization, her mission, was instrumental 1:07:48.200 --> 1:07:51.240 in shedding light on this disease, getting people to talk 1:07:51.240 --> 1:07:54.880 about their experiences and how the medical establishment was frankly 1:07:55.000 --> 1:07:59.959 failing them, and later on in navigating the very comp 1:08:00.040 --> 1:08:06.360 lloicated issues of testing, insurance, financials, genetic counseling. Because of 1:08:06.720 --> 1:08:11.640 all of these years of prejudice surrounding Huntington's and stigma 1:08:12.080 --> 1:08:16.240 and shame, there was sort of this like culture of 1:08:16.640 --> 1:08:20.160 almost like silence around the disease, so like even within families, 1:08:20.200 --> 1:08:24.840 it wasn't necessarily acknowledged. And I think that in more 1:08:24.880 --> 1:08:27.960 recent years, due in part and large part to this 1:08:28.120 --> 1:08:32.280 organization and other organizations that were founded, there's been a 1:08:32.320 --> 1:08:36.160 push to like increase awareness and to stop talking about 1:08:36.200 --> 1:08:41.599 it in these like, you know, eggshell tiptoe terms like hushed, 1:08:42.280 --> 1:08:46.240 Let's talk frankly about this disease and what we can 1:08:46.280 --> 1:08:47.800 do about it and what is you know, what are 1:08:47.800 --> 1:08:52.000 the different options, what is the research telling us, what 1:08:52.160 --> 1:08:56.920 support can be provided? And on the other side, of things. 1:08:57.000 --> 1:09:00.640 There was another organization that was founded more were on 1:09:00.720 --> 1:09:03.840 the scientific angle, on the scientific research angle, called the 1:09:03.840 --> 1:09:09.759 Hereditary Disease Foundation, started by doctor Milton Wexler, whose wife 1:09:09.840 --> 1:09:16.200 Leonora died of Huntington's. Also two of their daughters, one 1:09:16.280 --> 1:09:19.759 named Alice, is a historian, I believe, and she wrote 1:09:19.960 --> 1:09:22.639 like one of the books I read, oh wow. And 1:09:22.680 --> 1:09:26.160 another of their daughters, Nancy, is a geneticist that helped 1:09:26.120 --> 1:09:28.880 to do like a ton of Huntington's disease research. So 1:09:29.640 --> 1:09:33.519 very cool, that's great. So this foundation had a different aim. 1:09:33.640 --> 1:09:36.519 They wanted to understand the mechanism of the disease. So 1:09:36.560 --> 1:09:39.599 in the early nineteen sixties, researchers came across a large 1:09:39.600 --> 1:09:42.960 cluster of people with Huntington's disease in the Zulia region 1:09:43.040 --> 1:09:47.880 of Venezuela by the shores of Lake Maracaibo. In this 1:09:47.920 --> 1:09:51.800 group of people, Huntington's was at a particularly high prevalence, 1:09:52.160 --> 1:09:55.280 so there were even some people suspected of being homozygous 1:09:55.280 --> 1:09:58.800 for the trait, meaning they had two copies of the 1:09:58.920 --> 1:10:03.800 mutated aaliele. And this group of people was studied by 1:10:03.840 --> 1:10:08.160 the Foundation and ultimately just to sort of like long 1:10:08.200 --> 1:10:11.800 story short it in nineteen eighty three, a marker for 1:10:11.840 --> 1:10:15.519 the gene was found and its location was identified as 1:10:15.760 --> 1:10:18.840 being on the fourth chromosome, and ten years later, in 1:10:18.920 --> 1:10:22.160 nineteen ninety three, the last big point in the timeline 1:10:22.160 --> 1:10:27.040 of Huntington's disease so far, the exact gene was found, 1:10:27.200 --> 1:10:31.320 and isolating the gene for Huntington's disease was huge on 1:10:31.360 --> 1:10:34.639 the scientific front. It allowed for researchers to understand how 1:10:34.680 --> 1:10:37.720 this allele produced the effects that it did, to tried 1:10:37.720 --> 1:10:41.479 to come up with potential therapies, and from the patient's 1:10:41.520 --> 1:10:47.040 point of view, it held answers because identifying this gene 1:10:47.160 --> 1:10:49.040 meant that you could be tested for the disease. 1:10:50.479 --> 1:10:51.880 But it's not as simple. 1:10:51.720 --> 1:10:55.600 As that, of course, because with this new ability to 1:10:55.800 --> 1:11:00.240 test came a bag of ethical considerations since this was 1:11:00.240 --> 1:11:04.000 a heritable disease. So, for instance, if a parent did 1:11:04.040 --> 1:11:06.280 not want to get tested, but you did and you 1:11:06.400 --> 1:11:09.400 found out that you were positive, how do. 1:11:09.240 --> 1:11:09.880 You deal with that? 1:11:10.960 --> 1:11:12.960 And Erin, I know you're going to talk a bit 1:11:12.960 --> 1:11:16.240 more about this aspect, so I'm just going to kind 1:11:16.240 --> 1:11:19.519 of wrap it up here and say that we've come 1:11:19.600 --> 1:11:23.240 a long way in our understanding of Huntington's disease and 1:11:23.280 --> 1:11:26.799 how it works, and in reducing some of the stigma 1:11:26.880 --> 1:11:29.400 and shame that used to be so prevalent. 1:11:30.640 --> 1:11:34.080 But just like you said, in many ways. 1:11:33.680 --> 1:11:36.719 We are kind of right where we were at the beginning. 1:11:37.240 --> 1:11:40.439 So erin, I'm hoping that you'll tell me the ways 1:11:40.640 --> 1:11:43.559 that we've gotten better and maybe some hope for the future. 1:11:44.880 --> 1:12:21.880 I'll try to we'll take a quick break first, so 1:12:22.479 --> 1:12:25.559 before we talk a little more about the genetic testing bit, 1:12:25.680 --> 1:12:32.120 let's just quickly go over the numbers. Overall, the prevalence 1:12:32.280 --> 1:12:37.840 of Huntington's worldwide, on average is somewhere between four and 1:12:38.120 --> 1:12:43.040 ten per one hundred thousand people. Okay, it does vary 1:12:44.040 --> 1:12:48.479 quite a bit based on region, and we don't fully 1:12:48.640 --> 1:12:52.240 know why, like why this region is more prevalent than others, 1:12:52.320 --> 1:12:55.920 But in general, in Asia the prevalence tends to be 1:12:56.120 --> 1:13:00.400 far lower. That's where it's kind of the lowest worldwideestimated 1:13:00.439 --> 1:13:03.000 there at about zero point five per one hundred thousand 1:13:03.040 --> 1:13:07.360 people in western, Central and Eastern Europe. So all over 1:13:07.400 --> 1:13:10.840 Europe as well as the UK, prevalence estimates have varied 1:13:10.880 --> 1:13:15.320 between two and seven per one hundred thousand in Africa, 1:13:15.439 --> 1:13:18.280 where we don't have as good of estimates, they varied 1:13:18.320 --> 1:13:22.600 between one and four per one hundred thousand. In Oceania 1:13:22.880 --> 1:13:26.000 it's estimated at five per one hundred thousand, and then 1:13:26.120 --> 1:13:29.479 in North America seven per one hundred thousand. But this 1:13:29.560 --> 1:13:33.360 also varies a lot within North America, Okay, South America, 1:13:33.479 --> 1:13:36.639 outside of that region in Venezuela that you mentioned, which 1:13:36.720 --> 1:13:40.599 is much higher. We really don't have good numbers on 1:13:40.680 --> 1:13:43.720 like the rest of South America, very limited data, but 1:13:43.840 --> 1:13:48.000 so worldwide overall like five to ten per one hundred 1:13:48.040 --> 1:13:52.559 thousand people. And like I said in the biology section, 1:13:52.960 --> 1:13:56.880 the mean age of onset is around forty years, so 1:13:56.960 --> 1:14:00.800 thirty to fifty years, and then life expected see tends 1:14:00.840 --> 1:14:04.120 to be about ten to twenty maybe thirty years once 1:14:04.160 --> 1:14:09.280 symptoms appear, Okay, And that part doesn't vary based on income, 1:14:09.400 --> 1:14:14.599 based on country, based on anything. And that's largely because 1:14:14.640 --> 1:14:18.519 even though individual manifestations of this disease can vary, like, 1:14:18.560 --> 1:14:23.680 the overall course doesn't really vary. And the way that 1:14:23.720 --> 1:14:26.520 we deal with it in all these different countries, regardless 1:14:26.560 --> 1:14:33.200 of country's income doesn't really vary either. So to kind 1:14:33.280 --> 1:14:36.960 of get into both what we can do for treatment. 1:14:37.120 --> 1:14:39.880 And then also what you are mentioning Aaron about this 1:14:40.640 --> 1:14:45.960 ethical dilemmas when it comes to genetic testing. The bottom 1:14:46.040 --> 1:14:49.680 line is that right now, in terms of treatment, we 1:14:49.880 --> 1:14:55.720 have nothing that can change the course of disease. We 1:14:55.760 --> 1:15:00.400 don't have any medicines or treatments that can yes the 1:15:00.479 --> 1:15:06.440 underlying issues or the progression of disease. We have symptomatic treatments, 1:15:06.680 --> 1:15:11.240 especially for the Korea form movements, those involuntary motor movements. 1:15:12.400 --> 1:15:15.680 We have drugs that affect like dopamine pathways and some 1:15:15.840 --> 1:15:19.800 other things that can help with those involuntary movements. We 1:15:19.920 --> 1:15:24.320 also have drugs that can treat things like depression and anxiety, 1:15:24.960 --> 1:15:30.200 antipsychotics if psychotic symptoms develop, So we have those kind 1:15:30.200 --> 1:15:34.439 of psychiatric drugs, but we don't have anything specific to 1:15:34.520 --> 1:15:37.920 Huntington's and we don't have anything to address the underlying 1:15:38.040 --> 1:15:45.400 issue itself. And so in part because of that, this 1:15:45.560 --> 1:15:49.880 is not a genetic disorder like for example, cystic fibrosis 1:15:50.000 --> 1:15:52.960 or sickle cell disease that we've talked about before, where 1:15:53.120 --> 1:15:57.880 early identification can lead to vastly improved outcomes. Because of 1:15:57.920 --> 1:16:01.800 the treatment options that we have available right this is 1:16:01.880 --> 1:16:06.719 not that, and so genetic testing can tell a person 1:16:06.840 --> 1:16:10.360 that they have this gene and can tell them that 1:16:10.400 --> 1:16:15.439 they are going to develop Huntington's or not. But it 1:16:15.479 --> 1:16:18.479 has sparked quite a lot of debate about when and 1:16:18.640 --> 1:16:22.799 whether to do genetic testing, especially when it comes to children, 1:16:23.280 --> 1:16:27.040 like at what age should someone be allowed to decide 1:16:27.080 --> 1:16:31.280 that they want to get tested? Yah, But it also 1:16:31.400 --> 1:16:36.080 brings up ethics in regards to the idea that, of course, ethically, 1:16:36.680 --> 1:16:39.800 everyone has a right to know their own health status. Right. 1:16:39.920 --> 1:16:41.840 I have a right to know what's going on in 1:16:41.880 --> 1:16:43.840 my body. If there's a test that can tell me 1:16:43.920 --> 1:16:46.760 that I have a genetic disorder and I want to 1:16:46.800 --> 1:16:48.800 know it, I have a right to know that. But 1:16:49.479 --> 1:16:53.800 every person also has a right to not know. And 1:16:53.960 --> 1:16:56.640 I have a right to keep all of my information 1:16:56.960 --> 1:16:58.800 secret to me if that's what I want. 1:16:59.320 --> 1:17:00.000 Yeah. 1:17:00.320 --> 1:17:04.559 So, like you mentioned Aaron, a person getting genetic testing 1:17:04.600 --> 1:17:07.920 done for something like Huntington's that is autos almal dominant 1:17:08.560 --> 1:17:15.000 necessarily discloses information about the parents' health status, right that 1:17:15.120 --> 1:17:18.280 they may or may not have wanted disclosed. It also 1:17:18.320 --> 1:17:23.519 could release information about for example, an identical twin. Oh yes, right, 1:17:24.160 --> 1:17:27.040 and so there is a lot of kind of ethical 1:17:27.040 --> 1:17:28.160 issues surrounding this. 1:17:28.880 --> 1:17:33.240 So regarding all of these like ethical considerations and whatnot, 1:17:33.800 --> 1:17:36.920 do you know how much that happens to very country 1:17:36.920 --> 1:17:38.040 to country. 1:17:38.840 --> 1:17:39.759 Very good question. 1:17:40.360 --> 1:17:40.960 I do not. 1:17:41.560 --> 1:17:44.599 I imagine it could vary quite a lot, especially because 1:17:44.880 --> 1:17:48.200 when it comes to disease and how much people want 1:17:48.240 --> 1:17:53.320 to know culturally, that varies hugely in different countries. So 1:17:53.479 --> 1:17:57.600 in some places, like people don't want to know necessarily, 1:17:57.840 --> 1:18:02.240 especially if the outcome is going to be a right, right, 1:18:02.760 --> 1:18:09.760 And so I imagine that it varies quite quite a lot. Okay, Yeah, 1:18:10.080 --> 1:18:12.719 So there's not like it, there's not an answer to this, right. 1:18:13.160 --> 1:18:15.120 It's a very person specific and so this is the 1:18:15.200 --> 1:18:17.960 kind of thing that really has to be a discussion 1:18:18.040 --> 1:18:23.839 between an individual and their healthcare provider, yes, and genetic 1:18:23.880 --> 1:18:28.800 counselors especially. But Aaron I like to try to end 1:18:28.920 --> 1:18:35.320 these episodes on more hopeful notes. So let's talk. 1:18:35.160 --> 1:18:38.040 About the future gene therapy. 1:18:38.439 --> 1:18:42.200 Gene therapy, and really, I think that one of the 1:18:42.240 --> 1:18:49.360 things about how much we do know about Huntington's is 1:18:49.400 --> 1:18:53.240 that even if we don't know every detail about the 1:18:53.280 --> 1:18:58.280 specific mechanisms, we know a lot and we know enough 1:18:58.360 --> 1:19:02.559 to know that gene therapy is a real possibility for 1:19:02.800 --> 1:19:08.920 treatment of this disease. Yeah, and that's I think, really 1:19:09.080 --> 1:19:14.760 really incredible. So there are a lot of different possibilities, 1:19:14.800 --> 1:19:16.800 and there are people working on kind of all of 1:19:16.840 --> 1:19:19.879 these different I have links to a number of papers 1:19:19.880 --> 1:19:22.320 that go in a lot of detail on all of 1:19:22.320 --> 1:19:24.920 the different research that's being done and the different kind 1:19:25.000 --> 1:19:28.920 of ways that you could target Huntington's disease from a 1:19:29.000 --> 1:19:32.680 variety of different angles with gene therapy. So a lot 1:19:32.720 --> 1:19:35.720 of it is maybe using something like RNAi, which are 1:19:35.760 --> 1:19:38.559 little small pieces of RNA that can go in and 1:19:38.880 --> 1:19:42.360 kind of make changes. I think that the most exciting 1:19:42.400 --> 1:19:46.280 prospect is Crisper, Oh, Yeah, which we talked about in 1:19:46.320 --> 1:19:49.840 a lot more detail in the sickle Cell episode, because there, 1:19:49.880 --> 1:19:51.640 I think we're a little bit further along than we 1:19:51.720 --> 1:19:56.840 are in Huntington's. But Crisper, just for anyone who hasn't 1:19:56.840 --> 1:20:00.160 listened to that or who has forgotten, is a way 1:20:00.160 --> 1:20:03.519 by which you can go in to a cell and 1:20:03.680 --> 1:20:10.640 make very specific, targeted changes one time that persist for 1:20:10.720 --> 1:20:13.320 the life of that cell, So you can actually change 1:20:13.360 --> 1:20:19.320 the DNA very specifically and cut out that mutant Huntington 1:20:19.400 --> 1:20:23.519 gene and replace it with a non mutated like a 1:20:23.600 --> 1:20:27.439 normal type Huntington gene, and you can do so with 1:20:27.560 --> 1:20:32.400 one treatment, whereas most gene therapies that are in development 1:20:32.479 --> 1:20:36.240 would require a lot of infusions, which is especially difficult 1:20:36.240 --> 1:20:39.200 for neurodegenerative diseases where you have to be able to 1:20:39.240 --> 1:20:42.759 get that into the brain. So that requires going directly 1:20:42.800 --> 1:20:46.599 into the brain, which is very problematic or very difficult. Yeah, 1:20:46.760 --> 1:20:52.280 sounds very risky, Yeah, but there are a number of 1:20:52.320 --> 1:20:57.360 different strategies. Some gene therapies might try to reduce the 1:20:57.520 --> 1:21:01.080 expression of this mutant protein, so you might still make 1:21:01.160 --> 1:21:04.160 some of it, but you just wouldn't accumulate those toxic 1:21:04.280 --> 1:21:07.600 levels because you're making less of it, Okay. Others like 1:21:07.680 --> 1:21:11.040 I mentioned, especially Crisper, would just cut that mutated region 1:21:11.120 --> 1:21:15.479 out and replace it with a normal region. And then 1:21:15.479 --> 1:21:18.400 there are other therapies that are being developed aside from 1:21:18.439 --> 1:21:21.840 just gene therapy to try and address the downstream effects 1:21:21.880 --> 1:21:26.040 as well, like try and improve cognitive decline by addressing 1:21:26.080 --> 1:21:29.960 things like mitochondrial function, which we think is very involved 1:21:30.040 --> 1:21:34.840 in dementia and cognitive decline in general. So there's a 1:21:35.040 --> 1:21:39.800 lot of research being done. If you look at Clinicaltrials 1:21:39.840 --> 1:21:43.280 dot gov and you search for Huntington's, you can find 1:21:43.320 --> 1:21:46.840 over fifteen hundred studies that are being done. Not all 1:21:46.880 --> 1:21:50.840 of those are drug studies or treatment studies, but that 1:21:51.000 --> 1:21:54.600 is a lot. It's like on par with cystic fibrosis 1:21:54.640 --> 1:21:56.840 and things like that when you kind of just search 1:21:56.880 --> 1:22:01.000 for those studies. Okay, if you check, I'll link to 1:22:01.040 --> 1:22:04.440 a website where you can check specifically gene therapy studies. 1:22:04.560 --> 1:22:08.240 There are six studies currently listed on the gene Therapy 1:22:08.320 --> 1:22:11.920 Clinical Trial Database. Several of them are stem cell studies, 1:22:11.960 --> 1:22:15.000 because that's another possibility, is using stem cells to just 1:22:15.080 --> 1:22:18.559 like regrow the brain tissue that is damaged a whole 1:22:18.680 --> 1:22:21.679 nother mechanism, and some of those kind of addressed dementia 1:22:21.680 --> 1:22:25.840 in general, not just only Huntington's. But there are at 1:22:25.920 --> 1:22:29.599 least two gene therapy studies specifically that are in phase 1:22:29.640 --> 1:22:33.880 one and phase two trials, so human trials for kind 1:22:33.920 --> 1:22:36.480 of safety and feasibility. 1:22:36.840 --> 1:22:37.400 That's cool. 1:22:37.680 --> 1:22:41.719 Yeah, so it is on the horizon. And I'll also 1:22:41.760 --> 1:22:46.320 link to another Nature just sort of write up article, 1:22:46.760 --> 1:22:50.200 not like a peer reviewed publication, but an article about 1:22:50.479 --> 1:22:55.280 a group that's working on Crisper specifically for Huntington's. So like, 1:22:55.880 --> 1:22:58.280 there's a lot of hope, I think, and there's a 1:22:58.280 --> 1:23:02.559 lot on the horizon that that could potentially come to fruition. 1:23:03.120 --> 1:23:06.320 How quickly how many people currently living with Huntington's will 1:23:06.320 --> 1:23:08.920 be able to see those benefits, I don't know, but 1:23:10.000 --> 1:23:17.719 I believe it's possible. Yeah, Yeah, so that's Huntington's. Wow, 1:23:17.880 --> 1:23:18.760 that was a big one. 1:23:18.960 --> 1:23:20.840 It was. Yeah. 1:23:21.400 --> 1:23:26.040 So sources, sources, I want to shout out just a 1:23:26.080 --> 1:23:29.280 couple in particular. I have a bunch, but I want 1:23:29.320 --> 1:23:32.599 to shout out by Alice Wexler, the Woman who Walked 1:23:32.640 --> 1:23:39.280 into the Sea, and also a textbook by Bates, Harper 1:23:39.320 --> 1:23:42.919 and Jones called Huntington's Disease. Those had great history sections. 1:23:42.960 --> 1:23:45.200 And then I have a bunch of other additional papers. 1:23:46.040 --> 1:23:49.720 I also have a number of papers. Especially interesting, I 1:23:49.720 --> 1:23:54.840 think are the ones looking at the future targets for 1:23:55.000 --> 1:23:59.040 future clinical trials in Huntington's disease and the slowing of 1:23:59.240 --> 1:24:04.080 neurodegeneration in Parkinson's disease and Huntington's disease future therapeutic perspectives. 1:24:04.360 --> 1:24:06.479 You can find the list of all of our sources 1:24:06.520 --> 1:24:09.200 from every single episode on our website this podcast will 1:24:09.240 --> 1:24:11.040 kill You dot com under the episodes tap. 1:24:11.320 --> 1:24:14.360 Thank you again so much to Jay for providing their 1:24:14.400 --> 1:24:18.800 first hand account for this episode. We really really appreciate. 1:24:18.320 --> 1:24:21.680 It, Yeah we do. Thank you. Thank you also to 1:24:21.920 --> 1:24:25.240 Bloodmobile for providing the music for this episode and all 1:24:25.280 --> 1:24:26.120 of our episodes. 1:24:26.479 --> 1:24:28.960 And thank you to the Exactly Right Network, of whom 1:24:28.960 --> 1:24:30.400 we are very proud member. 1:24:31.200 --> 1:24:34.880 And thank you to you listeners. We really appreciate you 1:24:34.960 --> 1:24:38.599 listening to this podcast. We really like making it, even 1:24:39.000 --> 1:24:41.720 when it's a tough topic to talk about. Yeah, we 1:24:41.840 --> 1:24:42.200 really do. 1:24:42.320 --> 1:24:47.840 And we appreciate you sticking with us all this time, 1:24:47.960 --> 1:24:51.120 all this time, letting us make this podcast essentially. 1:24:51.360 --> 1:24:52.599 Yeah. 1:24:52.840 --> 1:24:57.519 Well, until next time, wash your hands you feelthy animals? 1:25:02.160 --> 1:25:03.080 Oh bu. 1:25:05.720 --> 1:25:06.639 Bu bu. 1:25:09.400 --> 1:25:13.880 Bumba bumbo 1:25:16.960 --> 1:25:17.800 Ombu