This episode features Western Washington University professor Dr. Jeff Carroll. In this show we talk about Huntington’s Disease (HD) and is the third in our neuroscience series (one each season).
We tackle a very serious illness with a combination of reverence and humor. Dr. Carroll takes us through the history of disease, his personal journey with the illness and his research on HD at WWU.
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Male: Here we go!
[♪ Blackalicious rapping Chemical Calisthenics ♪]
♪ Neutron, proton, mass defect, lyrical oxidation, yo irrelevant
♪ Mass spectrograph, pure electron volt, atomic energy erupting
♪ As I get all open on betatron, gamma rays thermo cracking
♪ Cyclotron and any and every mic
♪ You’re on trans iridium, if you’re always uranium
♪ Molecules, spontaneous combustion, pow
♪ Law of de-fi-nite pro-por-tion, gain-ing weight
♪ I’m every element around
Dr. Regina DeGraaff: Welcome to Spark Science where we explore stories of human curiosity. And we are here with Dr. Jeff Carroll. Welcome.
Jordan Baker: Hey! Glad you’re here. [laughter]
Regina DeGraaff: And our listeners can hear my wonderful co-host, the entertainer, the improv actor, the home inspector: Jordan Baker.
Jordan Baker: Yeah I switched careers since we last talked.
Regina DeGraaff: Yeah, so for our listeners that have been keeping up with us, for our like, you know, 5 loyal listeners that have been listening —
Jordan Baker: Thanks guys.
Regina DeGraaff: Yeah. Jordan used to be a butcher [pronouncing like “boocher”].
Jordan Baker: Boocher.
Regina DeGraaff: Yeah. That’s what I say! But he has moved away from that. So I mean, we’re talking about biology. You used to be a butcher. I mean, it’s all related.
Jeff Carroll: Same same.
Jordan Baker: Yeah
Regina DeGraaff: Yeah.
Jordan Baker: Exactly. That’s what I like to think!
Regina DeGraaff: So, we wanted to talk about lots and lots of stuff. But before we even do any of that, I like to ask our guests like how did they get into science? Like what was the thing — which I actually read your Wikipedia page, Dr. Jeff Carroll.
Jeff Carroll: Did your homework.
Regina DeGraaff: Yeah. And just to let our listeners know, Jeff is also a professor at Western Washington University. We also know each other through our children. Not that we have children together! [laughter]
Jordan Baker: I was like, “What?” [laughter]
Regina DeGraaff: But my child and his children do kickboxing together, so —
Jordan Baker: Oh.
Jeff Carroll: It’s a small town.
Regina DeGraaff: It’s a small town.
Jordan Baker: So he knows —
Regina DeGraaff: He knows Brooke!
Jordan Baker: Woah!
Regina DeGraaff: Who is also from Lynden and was in our past episode, “Kinesiology.”
Jeff Carroll: Whom my children only refer to as ma’am.
Regina DeGraaff: Yes, yes.
Jordan Baker: As they should.
Jeff Carroll: Yes.
Regina DeGraaff: Yes, as they should.
Jordan Baker: I’d be scared!
Regina DeGraaff: Yeah. So those loyal listeners, you just heard Brooke in “Kinesiology,” and now you have our connection.
Jordan Baker: Yeah.
Regina DeGraaff: So, how did you get into science?
Jeff Carroll: I wasn’t really scientific as a kid, honestly. I grew up — It wasn’t really pushed on me. I just went to public school and kinda nobody nudged me in that direction. You know, my parents never really pushed it and they were pretty distracted with their own stuff. And I sort of based on that, like around junior high, kind of stopped taking school very seriously.
Actually we just found my 9th grade Sequoia Junior High School transcripts. And they’re full —
Regina DeGraaff: This was in the Northwest, you grew up in the Northwest?
Jeff Carroll: Yeah, I grew up in Kent, which I’ll say.
Regina DeGraaff: [laughing] And you’re just like, “And I’m gonna stop at that.”
Jeff Carroll: Yeah, so based on like not being that into school and my parents having issues, I kind of drifted away from school generally. So we just found my transcripts and they’re really funny because like they’re a weird mix. Like I got an A+ in AP computer science cause I loved computers as a kid, and then like an F in honors English. And I’m thinking, “Who signs up for honor’s English and then gets an F?” [laughter]
Regina DeGraaff: Even like a C?
Jeff Carroll: No, F in 8th grade! I mean you have to try pretty hard in 8th grade honor’s English to literally get an F. And the note from the teacher was, “Shows no interest.”
I started a program called Running Start, which is like a way that you can leave high school and go to university early.
Regina DeGraaff: I also did Running Start. I left Jordan behind.
Jordan Baker: Yeah, well.
Regina DeGraaff: And I was like, “Screw you. You have to be in Lynden by yourself.”
Jordan Baker: Lots of people left me behind.
Regina DeGraaff: That’s true! [laughing]
Jordan Baker: But that’s a different topic.
Regina DeGraaff: Yeah. [laughing]
Jeff Carroll: So yeah, I start Running Start and I got very distracted. I loved being in college, but I wasn’t ready and disciplined or whatever. And so I kind of got into some trouble and I had some issues going on in my life where I was like . . . Had to really think about what I wanted to do.
And my friend and I decided the most punk rock thing we could do to like get out of Kent, Washington was to join the army, which was like obviously, none of our friends with like giant mohawks and nose rings or whatever were doing at the time. It just seemed really rebellious.
And we joined the army together, my friend Owen, and I. So you know, we walked into the recruiting station and Owen had this like 12-inch high liberty spikes that were dyed red, and I had like this 10-gauge circular barbell through my nose. And this sergeant Randy Quade, whom I still remember from Texas, stood up and like you could see him salivating.
And he was just like, “Come on in, boys.” And yeah, so he convinced us that we were going the right way. We joined the army, and I left. And so obviously, that was the end of any kind of school. So I left when I was 18 to join the army, and was sent to training in South Carolina and Georgia. And then I got my first duty station which was in Fort Lewis, Washington [laughing] which is 20 —
Jordan Baker: [laughing]
Regina DeGraaff: Because you wanted to come back!
Jeff Carroll: Right. So I always say only the army could look that deeply in your soul and just screw you, like —
Jordan Baker: [laughing] Right.
Jeff Carroll: Cause they could’ve sent me — I had people in my unit went to Australia, Korea, Germany — I was the only person of 200 that went to Fort Lewis, Washington, 20 minutes from home.
Regina DeGraaff: And you’re like, “I really wanted go literally anywhere else.”
Jeff Carroll: Anywhere else! I was 20 minutes from home. And so I was also like, I was 20 — no I was 19 and then 20. And so I couldn’t even drink. Like I couldn’t even go out to the bar with my army buddies cause I wasn’t legal drinking age. So I started —
Regina DeGraaff: You could’ve gone to Canada.
Jeff Carroll: Well, so I started spending my weekends in Vancouver, which I didn’t even know existed when I was a kid. I just like didn’t find out about it until I was a grownup. I was like “Woah, there’s like not just space between Washington and Alaska.”
Regina DeGraaff: Yeah, we lived on the border so we could see —
Jeff Carroll: You could see Canada.
Regina DeGraaff: Yeah.
Jeff Carroll: So I started going up there on the weekends and met a girl. And then I got orders for Germany, which is what I had always wanted, but it was just random, and went to Germany, lived in Europe for three years. My girlfriend, my Canadian girlfriend at the time, Meegan, decided to visit me in Germany, and when she visited we decided, “Hey this would be awesome if we could live here.”
But the army won’t let your girlfriend live with you, you have to be married. And so we’re like, “Hey let’s just shack up and get married and then we can travel,” you know, we can stay together, we can travel to Europe, we can — Not that I didn’t want to marry my wife, but the idea was that— [laughter]
Meegan if you’re listening, I’m sorry!
Jordan Baker: Sounds so magical! [laughter]
Regina DeGraaff: Yeah, he’s like, “You know what? You know what we should do? Let’s get married.”
Jordan Baker: “Let’s just do this.”
Jeff Carroll: Apparently literally I proposed by saying, “I think it’s best we get married,” actually.
Regina DeGraaff: Wow, that’s fancy!
Jeff Carroll: She’ll tell you that story. So I was in Germany, I got stationed, and then that was kind of around the time when the Kosovo War was happening and we knew that my unit was on call to be the peacekeeping. My unit was on call generally, so we were either gonna be the ones that invaded or the ones that went in for peacekeeping. They didn’t know what was gonna happen at the time. So there was bombing and there was air war, and then I was on leave while that was happening.
And we went home. And my dad, which is weird because my dad and my mom were divorced, but my dad sat my new wife and I down at the kitchen table and said, “Not only is your mom at risk for this brain disease, Huntington’s disease, but she’s actually starting to get sick.”
Meegan had literally never heard of it. You know, it’d be like if someone said, “You’re sick with blah blah blah disease.” Like Meegan had no frame of reference. And it suddenly crashed back down on me at that time that my grandma, who had been not in my life when I was a kid — She was in a nursing home and it was always kind of those vague family stories of why is she not around. You know, there’s kind of — Probably we should’ve put things together, but kids don’t, you know? They just believe their parents.
And we got told — My parents were really religious, and they said, “Oh you don’t have to worry about it. We got a blessing from the church and everything’s fine.” And I was like, you know, you’re a kid. You don’t question.
Regina DeGraaff: Yeah.
Jeff Carroll: And so then I realized, “Oh my grandma has it. That means it’s genetic. That means . . .” And I think I probably even knew somehow that it was 50/50, which is the genetics of the disease which is that the children of offspring — The offspring of people, rather, who have Huntington’s disease have a 50% chance of themselves having it. And if you have it, it’s not like you’re a carrier or whatever. Like, everyone who gets it dies. So it’s a fatal neurodegenerative disease.
And so I at that point was like, “Oh my god, I gotta learn all I can about this.” Went back to Germany, we soon got sent to Kosovo later that year. Meegan came home to Canada because there was no point sitting around waiting for me. And when I was in Kosovo, we were peacekeeping, luckily not fighting, and there was nothing to do, like literally nothing to do — Like walk around and check the wire again, and then try and find something to read. They were actually giving free correspondence courses to the troops who were deployed. Like, “Thanks America!”
Regina DeGraaff: Yeah!
Jeff Carroll: But I took biology 101 as a correspondence course there in Kosovo sort of like, “Okay I’m gonna try and figure this stuff out.” And you know, I finally realized this is not enough information for me. And so then I got out of Kosovo, had learned a little bit, but decided that when I got out, I’d go back to college.
My wife lived in Vancouver. We loved Vancouver. She had a condo there, so we went to Vancouver, and I applied for UBC. They admitted me as a philosophy major, like barely. And then I talked my way in to a first year science program. So you take calculus, and chemistry, and physics, and math, you know, everything, and biology 101. By the time they figured out I didn’t have any of the prerequisites, I was pretty far into it [laughing].
Regina DeGraaff: Oh wow. Awesome.
Jeff Carroll: And so it was really not a cool year, but I just kind of clawed my way through it and it was better than Kosovo and it was fine [laughing].
Regina DeGraaff: Yeah, yeah.
Jeff Carroll: And so then I was like, well I’ll just, you know, I’ll keep taking classes till I kind of know what’s going on with my mom and then I’ll like, you know, go to law school or something and get a real job. I just kept liking it.
Literally one of the world’s foremost experts on Huntington’s disease, both on like a biological level, like “How does the brain go wrong in this disease,” and on the clinical level, like taking care of people with Huntington’s disease, is this guy named Michael Hayden whose been at the University of British Columbia since the early 1980s.
Regina DeGraaff: So you’re just luckily that this dude is like right down the hall.
Jeff Carroll: Totally. So I started working for like the world’s foremost Huntington’s disease expert when I was in like junior in university. It just turned out really lucky in way.
Regina DeGraaff: That is quite the story.
Jordan Baker: Yeah.
Regina DeGraaff: Yeah!
Jeff Carroll: So that’s how I got into science.
Regina DeGraaff: Yeah. It took a war. It took like family history.
Jeff Carroll: It was like a pretty minor war, it wasn’t really — [laughter]
Regina DeGraaff: Oh, people from Kosovo, don’t listen to this! [laughter]
And that’s what I like about your story because I myself am a hypochondriac. Like, I will get very very stressed out and I will think the totally not true things are happening to me like my finger is hurting so therefore, I have finger cancer. You know stuff like that, which is ridiculous! So like even hearing your story, there’s even some anxiety in myself. But for some reason your story, because, you’re really tackling it. You’re learning about it so you can fight it and there’s some sort of, I don’t know, inspiring thing. And I mean that’s kind of a cheesy word, but I mean like, I don’t know. It’s a very “warrior scientist” tactic.
Jeff Carroll: Yeah, I’d like to think that, but I don’t usually. [laughter]
You know, I started in that mode, like “I’m gonna do this and I’m gonna go in there and I’m gonna be the one guy that changes the field,” and then you get in there and realize there’s lots of smart people working really hard on this. And like, the people around me were — Not that they were no less motivated than me for like personal reasons, but scientists generally are pretty motivated people, and especially people who work on diseases cause they tend to meet the people that they’re researching, right?
Regina DeGraaff: Right.
Jeff Carroll: And so even if they’re connected to these families, nobody works on Huntington’s disease and doesn’t get connected to families. And so, with any amount of time, Huntington’s researchers are very committed to this stuff. And so once I realized my connection to this disease is not some unique thing that I can drive this forward, I kind of had a grad school crisis, which I think everyone does.
Regina DeGraaff: Yeah.
Jeff Carroll: Like halfway through grad school when you’re like, “I don’t even know what my thesis is, and I hate everything, and this is a lame way to not make any money.” [laughing]
Regina DeGraaff: Yeah, exactly.
Jeff Carroll: So I went in and I told Michael, my supervisor, I said, “I’m gonna quit and I’m gonna move out to Pender Island in the southern gulf islands in B.C. and I’m gonna raise sheep.” And he was like, “I understand that you’re frustrated. Go to Pender and buy a sheep, but just commute into the city a couple days a week and we can work it out.” And I did it for like weeks, and I was like, “Farming sucks! It’s a really hard job.” I literally didn’t farm. I probably didn’t even have a garden out there, I don’t think. Maybe like a potted plant.
I just realized that wasn’t what I was gonna do. And then I kind of had this crisis. I had just had kids and I sort of realized like, you know, this sucks that I have Huntington’s in my life, but I have to do something with my life. I’ve gotta have a job. And so I really spent a significant amount of time sort of just thinking and being like, “Well I like science and I seem to be okay at it, and why not just keep doing this until it’s not the right thing to be doing anymore?” So it started as like, yeah I wanted be this inspirational figure. And now it just became like this is an awesome job, and I love doing science, and educating people, and that’s a pretty good thing to do every day.
Regina DeGraaff: So awesome. So, we’re going to take a quick break. And when we come back, we’ll kind of get into like, “What is Huntington’s disease,” and like “What’s happening to the brain,” and like “What do we know about it?”
[♪ Wondaland by Janelle Monae ♪]
♪ Early late at night
♪ I wander off into a land
♪ You can go, but you mustn’t tell a soul
♪ There’s a world inside
♪ Where dreamers meet each other
Jordan Baker: Welcome back to Spark Science. We’re talking to Dr. Jeff Carroll about neuroscience and Huntington’s disease. It says here in your Wikipedia, we’re cutting out calling it “HD.”
Jeff Carroll: Yes.
Jordan Baker: Don’t you think that it might get lost in some translations?
Jeff Carroll: It’s true.
Jordan Baker: Nowadays with the high definition televisions?
Jeff Carroll: It’s true. It’s like totally obvious to me that’s what we’re talking about and I get really confused when I’m having conversations with people and they’re like talking about resolution or whatever.
Jordan Baker: Right. “What? 1080p, I’m not sure.”
Regina DeGraaff: Right. If you could give us a good and about what is the disease, like what causes it and what happens?
Jeff Carroll: I mean people have known since 1872 that there are certain families that have this tendency to get, the Greek word for it is “chorea.” Not like the country, like C-H-O-R-E-A. And it means “dance” in Greek and it’s like a writhing, dance-like movement. So neuroscientists call it “hyperkinetic,” cause it just means you’re moving too much.
And so, you’ll see people and they look like they’re kind of twitchy or like they’re adjusting too much, but they’re doing it like way, way more than normal. And by the end stages, they’re often flinging their arms without control, like they have this incredible movement that they have no control over. You know, less appreciated then, but more now.
There’s also, in parallel with that movement problems, there’s cognitive decline. So people’s thinking ability goes down in lots of ways, like their memory. What neuroscientists call, “executive function,” which is like your top-down control over your own actions like stopping yourself from yelling at your kid, or whatever. That kind of stuff.
There’s mood disturbances. So people get depression, they get apathetic, anxious. And all of those things happen a lot more in people who have the mutation and, ultimately, the disease.
So it’s pretty rare — it’s a relatively rare disease. So there’s probably about 45,000 patients in the United States. And so it was known since then, since the late 19th century that there was this subset of families that had this genetic propensity to have these kind of symptoms, but nobody really knew why. It’s called Huntington’s disease after George Huntington, the guy who wrote that paper in 1872 describing it.
So obviously as sort of genetics got figured out more and more, people started realizing, “Well okay we can look at the pattern in the family and we say, okay is it like a recessive trait so that you have to get two mutant copies, or does it happen more often in boys or girls so we can say it’s linked to a sex chromosome?” And none of those things are true.
So Huntington’s is what’s called an autosomal dominant disease. An autosome just means it’s not on one of the sex chromosomes, X or Y in people. So boys and girls are just as likely to get it. And dominant means that you only have to have one bad copy of the gene to get it. So unlike sickle cell anemia where you have to inherit two mutant copies, one from mom, one from dad, Huntington’s patients usually — almost always, in fact — just inherit one mutant copy from either mom or dad who’s sick.
And so if you inherit that mutant copy, those bad symptoms happen to you. They progress, they get worse and worse, and then within about ten or 15 years from the beginning of those movement symptoms, people die.
As far as we know, there’s nobody in the world that’s had this mutation that didn’t die from the disease. It’s what geneticists call “100% penetrant,” meaning that everybody who has the mutation will have the disease. You know, other diseases, sometimes like you could be at risk for it rather than actually getting it, but for HD the gene is totally predictive.
And it wasn’t until in 1984, a group of researchers in Boston — Actually it was the first human disease gene that was what we call “positionally cloned,” meaning that instead of saying like, “Oh it’s in your gene somewhere,” we could say, “It’s on the short arm of chromosome 4,” right? It was linked very early to a specific region of a specific chromosome. In that day, you could say, “Okay well we can test with some amount of error whether you’re likely to have inherited the mutant copy from mom or dad before you get sick.” And it wasn’t perfectly predictive, but it was kind of revolutionary.
And it took ten more years of walking down that little neighborhood of the chromosome, using the kind of primitive genetic techniques they had at the time — which they developed so they weren’t really primitive, they were cutting edge then — but it took them ten more years to find the specific gene. And so now we sort of self-referentially call that gene the Huntington gene.
And they found a spelling mistake, actually an expansion of a natural sequence that’s there, sort of a genetic stutter. And if it’s expanded beyond a certain threshold, you’ll absolutely get Huntington’s. And in that first paper in 1993 when they identified the gene, they were able to say, “Look we’ve looked at, I don’t know, 600 Huntington’s patients or something and every single one of them have this mutation, and not one of the people we looked at that didn’t have Huntington’s had the mutation. Perfectly predictive.”
So that revolutionized everything because from then on, in theory from conception, you could test anyone from an HD family. Legally nowadays, we’re only allowed to do it to people who are 18 or over, but in theory there’s literally no more mystery. It used to be like, “Oh, you know, you look like Uncle Nick so I think you’ve got the disease.”
Regina DeGraaff: Right.
Jordan Baker: Wow.
Jeff Carroll: And it left all this shame and controversy within families, and all that just kind of went away. Unfortunately, people don’t use the test very much. My whole family has, but most people don’t. So yeah, that’s the kind of symptoms. The characteristic thing is that motor disturbance and then all the other stuff that goes along with it, and it progresses towards death, unfortunately.
Regina DeGraaff: I watched the short video on the Wikipedia page for Huntington’s disease and at first I was like, “Okay I get this. I get what’s happening.” And then it just went off into so much terminology that I didn’t understand and I was like, “Okay, well there’s cartoons so I’m just gonna keep on watching.” [laughter]
Jordan Baker: “And hopefully I get it!”
Regina DeGraaff: “Hopefully I get like one every 20 words.”
Jeff Carroll: Yeah.
Jordan Baker: It sounds — I don’t know much about diseases or anything cause, home inspector, but Parkinson’s — isn’t that where you lose control of your body? How similar is that to —
Jeff Carroll: Yeah, no it’s a really good question. So actually Parkinson’s and Huntington’s disease both result form degeneration of the same part of the brain. It’s sort of different little subparts of that same structure, but the same loops.
The movements are a little different. So in Parkinson’s disease, people have like a tremor, right? Like just really fluttery hands. And that tremor doesn’t look like real movement. It just looks like static, you know, like white noise.
The movements people do in Huntington’s disease, it almost looks like little fragments of what we call “intentional movement.” Like, “Oh I meant to reach for this cup,” or whatever, but it’s just random. And instead of being tied to like wanting to achieve this goal, it just happens. But then they find themselves with their hand extended towards nothing and then they like fling it back to their body and that leads to this kind of writhing, dancy movement. But the part of the brain in particular, a set of structures called the basal ganglia, are the same ones that die in both of those diseases.
Jordan Baker: Basal ganglia.
Jeff Carroll: Yeah. You learn something every day!
Jordan Baker: [laughing]
Jeff Carroll: One thing about the difference between the two — One important difference between the two is 100% of Huntington’s disease is genetic, so everyone who has, what I’ll call maybe “HD” from now on?
Regina DeGraaff: Yeah, HD!
Jordan Baker: It’s fine. [laughing]
Regina DeGraaff: It’s fine. We got it!
Jeff Carroll: Everyone who has HD has a genetic mutation in a specific gene. In Parkinson’s disease, about 85% of the people who have it do not have a genetic mutation that explains it. They just got unlucky or they had some environmental insult, or something we that don’t understand — kind of like lots of cancers where there’s rare genetic forms, but most people just get it. You just unlucky. And that’s how Parkinson’s is.
[♪ Wondaland by Janelle Monae ♪]
♪ Dance in the trees
♪ Paint mysteries
♪ The magnificent droid plays there
♪ Your magic mind
♪ Makes love to mine
♪ I think I’m in love, angel
♪ Take me back to Wondaland
♪ I gotta get back to Wondaland
♪ Take me back to Wondaland
♪ She thinks she left her underpants
♪ Take me back to Wondaland
Jordan Baker: If you’re just joining us, this is Spark Science. I’m Jordan Baker. Today we’re interviewing Dr. Jeff Carroll, neuroscientist. Has there ever been two Huntington carriers, I guess we’ll call it, mated —
Jeff Carroll: Yeah.
Jordan Baker: And had a child?
Jeff Carroll: Yeah. So in genetics that’s called — So when I say that almost every Huntington’s patient has one mutant gene, in genetics, we call that being heterozygous. And it means you’ve got one good copy from one of your parents and one bad copy. What you’re talking about is if two Huntington’s patients had a baby and that kid, unluckily, inherited a mutant copy of the gene from both parents.
Regina DeGraaff: Yeah.
Jeff Carroll: That’s called a homozygous patient. So somebody who has both mutant copies. That does happen. It’s super rare. It happens more in places where there’s like really tiny villages where people live. So there’s a couple isolated communities, one around the shores of Lake Maracaibo in northern Venezuela. There’s a massive, really high incidence of Huntington’s disease. So northern California, way up north in Quebec, there’s some villages where there’s what we call “founder effect” and there’s sort of like a lot of people up there who have it.
And so from those communities, we have some — like maybe tens of patients that are what we call homozygous. The really weird thing about them is we have no idea why, but they’re no worse than you would expect if they had the same mutation but only one copy.
Jordan Baker: Huh.
Regina DeGraaff: Huh.
Jeff Carroll: That’s one of the only human diseases I know of that has that truth, and that’s a very weird thing.
Jordan Baker: Wow.
Regina DeGraaff: So the little video that I was talking about before with the cartoons talked about the more generations there are that have the Huntington’s disease, the earlier the onset of these symptoms will happen. So I was thinking, when were saying that about having the two parents, having the two genes — Does that mean they get it, the onset of the symptoms earlier? But you’re saying no.
Jeff Carroll: No. I mean we don’t have that good of math here, cause we only have — you know, we have many thousands of people who have one mutant, and only tens of people that have two. But as far as we can tell, they have onset exactly when you would predict from the severity of their one mutation.
So yeah, the phenomenon you’re talking about is something called anticipation which is — it happens in other genetic diseases, and is the tendency over time for people to get the disease earlier than their parents did, which leads to like an obvious conundrum because like on a population level, then eventually people will get sick so early they won’t have kids. And you know, that population will die out.
And in fact, that would happen. And in fact, there are people who have really severe Huntington’s disease mutations that actually get sick as a kid. So I was just speaking with a neurologist in Seattle about a case of a kid who died around the age of 6, like died at 6, and had a really severe mutation — that stutter that I talked about was like stupendously large, and that’s just unlucky. So that happens generation to generation. But obviously there has to be an input to that too, right? If people are getting sick and kind of aging out of the population.
And previously — So when I learned undergraduate genetics in 2003, I got taught about Huntington’s. They used it as an example. And they taught us, by definition, that to have Huntington’s, your parent had to have it. Cause it’s that dominant thing, right? So you have to get it from someone who has it. And there was no, what they call, “new mutations,” meaning someone who just showed up and had a mutation and no one knew why.
And we’ve learned subsequently that it’s actually not true. If it was true, that anticipation thing you’re mentioning would like, no one would ever — they’d just be gone.
Regina DeGraaff: Right.
Jeff Carroll: And what we’ve found out now is actually — I don’t want to freak everyone out, but — [laughter]
Regina DeGraaff: That’s what this show’s for!
Jordan Baker: [laughing] Please do!
Regina DeGraaff: Please do. And spoiler alert, go ahead.
Jeff Carroll: There’s like a little sort of intermediate range of that stutter that will never cause the person who has it to get Huntington’s. But it can, in rare but not totally rare situations, expand when their egg or sperm cells get made, a process we call meiosis. And that can lead to their kids getting Huntington’s, leading to what we would perceive as a new mutation, right? Like somebody’s parent’s not sick, but they just showed up in a clinic. And that was supposed to not happen. And when the people who have the biggest databases of patients looked at this, they realized as many as like ten percent of the people in their databases are like verified to have new mutations.
Regina DeGraaff: Wow.
Jeff Carroll: And they were like, “Well how the hell did that happen?” So then we started to going to other genetic databases that we have now of like thousands of, you know, people who showed up for like a cardiovascular genetic study or whatever. And we took all these other DNA people, you know just from the general population, and sequenced their Huntington’s gene and found that what we call these intermediate alleles, right? These like not disease-causing, but potentially expandable mutations, happen in as many as like four or five percent of the population.
So even if all the Huntington’s patients were to like die, it’d still happen, right? It’d still come in and —
Regina DeGraaff: Wow.
Jeff Carroll: This is depressing. [laughter]
Regina DeGraaff: No! It’s like fascinating.
Jordan Baker: Yeah.
Regina DeGraaff: I don’t know. I just like — This is awesome. It’s not awesome, it’s bad. It’s sad, very sad. But it’s just — As a scientist, it’s just super interesting.
I wanted to possibly ask you about the area. So you were talking about, there’s like Venezuela. There was a hotspot. And then there was another hotspot in northern California. Where are these regions that you talk about?
Jeff Carroll: So George Huntington, this guy who wrote this paper talking about the disease, he was a family physician. He was a really young guy, like early twenties when he wrote it. So it was basically like his med school graduation project, kinda.
But his father and his grandfather had been physicians. So he had like three generations of experience. And they lived near the Hamptons, which I don’t think was the Hamptons then. I think it was just some villages on Long Island.
And they had seen these families and they would’ve had to have seen them over generations to realize some of the patterns that he picked up which is that — sort of word story but — that writhing, like really high intensity random movements, the chorea, it’s called, used to happen a lot.
There’s like a — if people get rheumatic fever which is one of the diseases we mostly got rid of here, there’s like an autoimmune thing that can happen after you get it and it attacks that same brain region. And so you get kids, like six months after they had rheumatic fever, would show up with like this twitchy weird movement that would sometimes go away and sometimes not.
So he was used to that as a symptom, but it took a lot of acuity to realize there was a different set of that same symptom, right? Like people who got it in the family, people who got it later. And that was his kinda great contribution.
The interesting thing about the families that Huntington studied though was they were in this place that turned out to be kind of interesting in different ways. So it’s very close to a huge molecular biology lab called Cold Spring Harbor Laboratories which is really a prominent — still prominent molecular biology research lab out on the shores of Long Island. They do a lot of marine biology, but also just fundamental molecular biology. It’s currently headed by Jim Watson, the guy — like Watson and Crick, Watson.
Regina DeGraaff: Oh wow.
Jeff Carroll: So it’s like a big deal.
Jordan Baker: Oh yeah.
Jeff Carroll: [laughing]
Regina DeGraaff: Watson and Crick. You wanna, you wanna —
Jordan Baker: Nope!
Regina DeGraaff: Yeah, no? Okay.
Jordan Baker: Let’s just move along. [laughter]
Regina DeGraaff: Let’s just move — okay!
Jeff Carroll: Sorry that was —
Jordan Baker: They can google it as they listen.
Regina DeGraaff: It’s a big controversy. It’s a good story actually.
Jeff Carroll: I will hold my tongue about Jim Watson. But he and Crick —
Regina DeGraaff: [whispering] He’s not a great guy!
Jordan Baker: Okay.
Jeff Carroll: A little racist.
Regina DeGraaff: Yes.
Jeff Carroll: A lot racist. He and Crick co-discovered the structure of DNA. So the double-helical structure of DNA was described in the 50s by them and the woman that they —
Regina DeGraaff: That they totally exed out of their research. They’re like, “We did it. Not her!”
Jeff Carroll: Interestingly, Crick —
Regina DeGraaff: Racist and sexist!
Jordan Baker: Right. [laughter]
Jeff Carroll: Crick, the other guy, went on to become a neuroscientist. He like figured out DNA and then he was like, “Okay that’s done so now what’s –” [laughter]
And he didn’t just become a neuroscientist. He became interested in consciousness, which we aren’t that good at as neuroscientists yet. He spent the rest of his life — cause he’s like Crick so he was like, “I can do whatever I want now.”
Regina DeGraaff: Yeah.
Jeff Carroll: So well after Huntington was there, like in the early 1920s and 30s and so on, there was this big movement in America called the eugenics movement, which was this idea of like —
Regina DeGraaff: Ugh.
Jeff Carroll: Right. Like —
Jordan Baker: I read that!
Jeff Carroll: They thought they understood genetics, right? And so they’re like, “Well let’s use this to purify the race or make a master race,” or whatever. And they —
Regina DeGraaff: Right. Which is, you know, the next step. [sarcasm]
Jeff Carroll: It’s obvious! [sarcasm]
Jordan Baker: Clearly. [sarcasm]
Regina DeGraaff: Yeah.
Jeff Carroll: So —
Jordan Baker: Which is why we’re here today!
Regina DeGraaff: Right, right. [laughter]
Jeff Carroll: Cause they failed.
Regina DeGraaff: Yeah.
Jeff Carroll: It’s interesting, I always say that like they knew as much genetics as like the alchemists knew chemistry, right?
Regina DeGraaff: Right.
Jeff Carroll: They had just like some kind of phenomenological, “Oh I can track pedigrees,” but they had no understanding of even what a gene was.
So the eugenics thing was linked to that lab because this sort of intellectual leader of the eugenics movement in the United States was a guy named Charles Davenport, who was professor at a little place called Harvard. And then he took over the Cold Spring Harbor Lab, and went there, and founded what’s called the Eugenics Record Office. And it was basically the American database of people with genetic disease.
And he went out — he actually had his secretary, of course, go out [laughter] — a woman, it’s not on any of his papers [laughter]
Jordan Baker: Undocumented worker.
Jeff Carroll: Yeah. And like catalogue — and they used Huntington’s as a paradigm example. And they went out and they mapped all these Huntington’s families. They weren’t like killing them, granted, but they were mapping them. And he wrote up their results in the PNAS, which is still like one of the top journals in the world.
His paper was basically like, “Well here’s this obviously dominant trait. It’s very easy. Just don’t have babies with those people.” And his last paragraph is like, “I’m really surprised those people just don’t stop marrying,” and you know, in a time when like you had to get married to have sex, like —
Regina DeGraaff: Right. [laughter]
Jeff Carroll: Good luck with that plan, buddy!
Regina DeGraaff: Right.
Jeff Carroll: So yeah. So that was right there. So we’re talking like tens of miles I don’t know wherever, but [inaudible] big, but on the same area as where George Huntington saw those families.
So yeah. I don’t know that it’s a hotspot, but it’s a place with a lot of history.
Regina DeGraaff: I love that story. So we’re gonna take a quick break and then when we come back, we’re probably gonna talk more about the future of what we can do for this work, but also, how is your field portrayed in pop culture?
Jeff Carroll: Mm.
Regina DeGraaff: Perfectly, I’m sure.
[♪ Wondaland by Janelle Monae ♪]
♪ Take me back to Wondaland
♪ I think me left me underpants
♪ The grass grows inside
♪ The music floats you gently on your toes
♪ Touch the nose, he’ll change your clothes to tuxedos
♪ Don’t freak and hide
♪ I’ll be your secret santa, do you mind?
♪ Don’t resist
♪ The fairygods will have a fit
♪ We should dance
♪ Dance in the trees
♪ Paint mysteries
♪ The magnificent droid plays there
Regina DeGraaff: Welcome back to Spark Science. We’re talking to Dr. Jeff Carroll about Huntington’s disease. We’re talking about neuroscience. And what I wanted to ask is like, what is exciting about your research and about your field right now? And what are you doing? What kind of research are you doing at Western?
Jeff Carroll: So you know, the fact that Huntington’s disease is a purely genetic disease gives you some hope, right? So if you look at other more common brain diseases like Alzheimer’s disease, they have a really hard time coming up with therapies, because by the time you recognize someone’s sick with dementia, they’re like pretty far progressed already.
Regina DeGraaff: Right.
Jeff Carroll: In Huntington’s, we don’t have that problem. We can identify people, as I said, from like when they’re a zygote or whatever. Like we can pop off a cell and test it. So we have this benefit that we can treat people. In theory, we can treat people before they get sick which is obviously the goal.
And the other thing is that because it’s what we call a “monogenetic disease,” so a disease caused by one gene, we have various technologies now and have since, well the early 90s actually, of selectively reducing the activation of individual genes.
So, you know, you’re born with 25,000 or so genes, but not every single one of them is on in every single cell of your body. Like your brain cells make brain genes and your toe cells make toe genes, and they turn on whatever set they need.
Jordan Baker: Toe genes. [laughter]
Regina DeGraaff: Yeah. I enjoy that too. I don’t know anything about —
Jordan Baker: The little cozy toe gene! [laughter]
Regina DeGraaff: I don’t know anything about biology and I’m like, “You know, the arm bone,” and they’re like “Ugh.”
Jeff Carroll: I may be slightly paraphrasing it, but —
Regina DeGraaff: Yeah. [laughing]
Jeff Carroll: But basically, so you can turn on and off genes. And we know a little bit about how to sort of hack that system and cause one particular gene to not be turned anymore. And that’s what’s called a gene silencing approach to therapy. Like, “Okay let’s give people a drug that, we don’t know what else this whole gene does once it’s on, but let’s just turn it off.” That’s advanced a lot.
There are some of these that are just — they’re finally being in the clinic. So there’s a company, Ionis Pharmaceuticals that’s in Carlsbad, California. I’ve been working with them for a long time since grad school and they have a drug. It’s a little unfortunate in that it has to be delivered into the spinal fluid cause it doesn’t cross the blood brain barrier.
Regina DeGraaff: Ew!
Jordan Baker: Ugh. [inaudible]
Jeff Carroll: And in monkeys and in all the other animals we’ve tried it in, when you deliver their drug, it does what it’s supposed to do. It gets throughout the brain, you know, it rides around the spinal fluid, the cerebral spinal fluid, and it goes into all the brain cells throughout the brain, and it reduces the Huntington gene.
And in every animal model we’ve ever done that with, if we give them a mutant Huntington gene, they get sick. If we give them this drug, they get better.
Regina DeGraaff: Hmm.
Jeff Carroll: So Huntington silencing, or Huntington lowering, this approach is the most exciting thing for sure. And Ionis, after a decade and a half of work on this, almost a decade of work, has what’s called a phase one human trial happening right now.
And so phase one is like, it’s technically a safety trial. And so it’s not really to see whether the drug works or not. It’s just to like put the drug in some people and see if they’re not, you know, they don’t die unexpectedly. [laughter]
And in this case, because the trial is so like invasive, right? You gotta get a needle jabbed in your spine. The FDA, rather the regulatory agencies in Canada and Europe which is where the trial is happening, let them run it in Huntington’s patients so they at least get a tiny bit of data. It’s not enough people to see much, but it’ll be at least be some data from people as to whether we made certain markers in their brain get better.
And there’s a lot of excitement about this. And that trial should finish, I think in 2017 is — they’re done collecting data.
Regina DeGraaff: So it’s like happening right now.
Jeff Carroll: Yeah there’s 36 people in the world walking around with this drug in their spinal fluid right now.
Regina DeGraaff: Wow.
Jeff Carroll: And we don’t know if they’re better or not, but we will know soon and that’s huge. And that’s like — so while that was happening there’s — I’m sorry to go on a tangent here but there’s another —
Regina DeGraaff: No, that’s what we’re here for! That’s what you’re here for!
Jeff Carroll: We’re all about the tangents. There’s a really horrible muscular disease of children called spinal muscular atrophy. And it’s actually the most common genetic form of death in kids. And kids are born normal and then they start having motor dysfunction. Like they learn to walk and then they start not being able to walk, and then eventually they can’t breathe, and they die, and it’s horrible.
And so kids with the worst of these types, spinal muscular atrophy type one, they die like before the age of five or six or something.
And Ionis, this company, had a different drug targeting a different gene, but the same kind of chemistry, same kind of delivery, same idea. And that drug was being tested in a more advanced study, we’ll call phase three study, which is actually, “Does this drug make people better or not?”
And the FDA, last year in 2016, halted that trial early because it was working so well. And they said, “It’s working so well that it’s unethical to keep people on placebo,” right?
Regina DeGraaff: Right.
Jeff Carroll: To like see if the drug worked or not. It’s so great, it’s unethical to keep these kids not getting active drug.
Regina DeGraaff: Right.
Jordan Baker: Wow.
Jeff Carroll: So that drug got approved this year for spinal muscular atrophy type one. So there’s great hope that —
Regina DeGraaff: So how well was it helping?
Jeff Carroll: Well the kids are alive.
Regina DeGraaff: Yes, okay.
Jeff Carroll: And we — so we have pretty anecdotal data on this. They walked a little better and stuff, but we don’t have a complete picture yet and won’t for years probably. But like you can get on YouTube and there’s moms who are like, “You know, my kid should be dead by now, and here he is relearning how to walk and ride a bike.”
Regina DeGraaff: Wow.
Jeff Carroll: So in some cases anyway, at least anecdotally, it looks really great. And on whole, the data was enough to convince the FDA that it’s gotta get moved forward. I’d love to have that happen in Huntington’s, that the trials that are ongoing now are so awesome that the FDA swoops in and says, “Hurry up and give this to everybody.”
So that’s what’s most exciting. And then, so you asked about my work. And as I said, I was involved in that work with Ionis a lot during my PhD. And subsequently I’ve been working with them now that I’m at Western.
And I’ve been — I sort of switched attention cause we kind of — like that got so advanced that it went off to the clinic. And I’m not a real doctor, I’m not a neurologist, so I don’t really have anything to contribute to that trial getting run well.
Jordan Baker: You’re a real doctor to me.
Jeff Carroll: [laughing]
Regina DeGraaff: That’s how my mom introduces me to people.
Jeff Carroll: Really?
Regina DeGraaff: She’s like, “My daughter’s a doctor. But I mean, not a real doctor, but.”
Jordan Baker: [laughing] Seems like a legit thing. I don’t know. I wouldn’t go to school that long and tell you that!
Regina DeGraaff: That’s true. Very sad for me.
Jeff Carroll: Definitely some selection pressure for the morons who are too dumb to stop going to school.
Regina DeGraaff: Yeah that’s right, that’s right. [laughing]
Jeff Carroll: So like the human stuff was so exciting, but it’s not really something — it’s not my work, right? I don’t do that. And so I kind of, again, I had another sort of reflection point. I was sort of like, “Well what do I wanna do now?”
And there are other approaches to that kind of silencing that won’t only silence Huntington in the brain, it would silence it all over the body. And that’s not what Ionis is doing, but that’s a possibility for future trials.
And one of the things about Huntington that makes it a really interesting science problem, but a really crappy disease problem is that we basically don’t know what this gene does. So the gene could’ve been in some really simple gene that tells cells how to break down sugar, or something that we could easily understand.
But the Huntington gene is totally mysterious. It’s conserved. Like slime mold have it, like amoebas have a Huntington gene, fruit flies, sea urchins, fish, dogs, us. Like everybody’s got a Huntington gene. It’s found in every cell of your body, not just your brain cells, which would be an easy explanation for why they die, but it’s not it. So every cell we’ve looked at has Huntington in it.
And so, I sort of said, “Well we should probably try to figure out what happens when we get rid of Huntington in cells. If it’s so important, like maybe we would should check that out.”
So once the silencing stuff went off to human trials, I basically kind of redirected my lab a little bit and said, “Let’s start like,” the genetic term is “knockout,” but like, “Let’s start getting rid of this Huntington gene.”
If you do it globally — like it’s relatively easy to do this in mice, it’s an established thing to do — but if you make mice that have no Huntington gene at all, they’re never born. Like their fetuses don’t develop and they resorb into their mother’s uterine wall and they’re never born, and —
Regina DeGraaff: Wow!
Jeff Carroll: Yeah, right.
Regina DeGraaff: That seems —
Jeff Carroll: Seems bad. [laughing]
Regina DeGraaff: It seems like it’s important.
Jeff Carroll: Yes. And there’s some data from brain cells, especially early in development when the brain is still developing, if we shut Huntington off, those brain cells that don’t have it on will die. We don’t think that happens in adults, we don’t think. But we definitely need to check those things out.
So I’ve switched my lab to like — I mean, A, cause I’m just curious and one of the best ways to figure out what a gene does is just get rid of it. You know, embryos that are never born are not very interesting to study cause there’s nothing to study.
So we started making mice that lack Huntington in different organs. So like we’ve made mice that don’t have Huntington in their liver. And like, there’s probably not huge problems in the liver in Huntington’s disease, but there’s a Huntington gene there. And so now I have mice that have Huntington gene everywhere and they’re born, which is handy, but they don’t have any Huntington in their liver. So I can study their liver, and poke and prod it, and like try to figure out what’s different about this liver compared to a normal liver. And maybe those differences will teach us about what the Huntington gene is doing.
[♪ Wondaland by Janelle Monae ♪]
♪ Take me back to Wondaland
♪ I gotta get back to Wondaland
♪ Take me back to Wondaland
♪ She thinks she left her underpants
♪ Take me back to Wondaland
♪ I gotta get back to Wondaland
♪ Take me back to Wondaland
♪ she thinks she left her underpants
♪ This is your land
♪ This is my land
♪ We belong here
♪ Stay the night
♪ I am so inspired
♪ You touched my wires
♪ My supernova shining bright
Jordan Baker: Today we’re talking about neurobiology with Western’s own, Dr. Jeff Carroll.
Regina DeGraaff: So I wanna — I mean I — every guest we have, we start talking about pop culture, but I have a great segue because you were a subject of a 2012 documentary. And do you wanna tell us a little bit about that? And how was that experience?
Jeff Carroll: You know, when I was in grad school, I did a lot of press and TV interviews and stuff about Huntington’s. I was really into raising awareness. I guess, in theory, I’m still into raising awareness. [laughing]
Regina DeGraaff: Yeah. I mean, you’re on a much lesser show like us, but — [laughter]
Jeff Carroll: It’s really been downhill since — yeah. [laughter]
Jordan Baker: We just got the toilet’s working.
Regina DeGraaff: We did.
Jeff Carroll: So I got this call. Actually I’d just moved from Boston. I was doing a post-doctoral fellowship at Mass General and Harvard Medical School, and I was living in Boston with my family. And I got a phone call from this guy — director and the producer of the movie — and they were saying, you know, “We’ve decided to do this film project on Huntington’s disease and specifically the like decision to either test or not test for the mutation. And we’re gonna pick a couple families, and we’re gonna follow them around, and we’re gonna film them.” And I was like, “No. Ugh.”
But John Zaritsky and Kevin Eastwood, the filmmakers, were amazing and they did a great job with it. I mean, I’ve only seen it twice. I saw it once when they brought it to our house to show it to us before they showed it to anyone else, and I saw the premiere, and I don’t watch it since then. It’s like listening to yourself on like a voicemail or something. It’s really awkward.
Jordan Baker: It’s the worst.
Jeff Carroll: So bad.
Regina DeGraaff: Yeah Jordan doesn’t listen to our show, but you know — [laughter]
Jeff Carroll: Someone has to!
Regina DeGraaff: I have to! Every single time, Jordan. [laughter]
Jordan Baker: You’re welcome?
Regina DeGraaff: Yeah. [laughter]
Jeff Carroll: So like — Yeah so I haven’t seen it a lot. But when I did see it, I remember it being quite good.
Regina DeGraaff: [laughing]
Jeff Carroll: And they covered the —
Regina DeGraaff: It’s called Do You Really Want to Know?
Jeff Carroll: Yes.
Regina DeGraaff: It came out in 2012, a documentary.
Jeff Carroll: Yeah and we showed it here at the Pickford one time. We’ve been talking about doing that again. Pickford’s a great theater here in town and we’d like to show it again.
Regina DeGraaff: It’s right next to the Spark Museum where we’re recording right now.
Jeff Carroll: It’s an awesome movie theater. And we had a great crowd of people really interested in these issues. You know, it’s not just Huntington’s. You know, as we learn more and more about genetics, maybe there won’t be things as kind of obvious and like dangerous as Huntington’s disease, but like everybody’s got some kinda genetic skeletons in their closet and eventually we’ll find all those, and people have to learn to live with genetic risk.
And maybe not quite so extreme as HD, but like — you know, the example of BRCA2 mutations and people, you know women who have these mutations have a much increased incidence of breast and ovarian cancer, and it’s sort of like how do you cope with that? You know?
Regina DeGraaff: Mhm.
Jeff Carroll: That’s sort of — I hate to say this even slightly, but sort of in a way even less extreme than Huntington’s in the sense that it’s 100% fatal in the case of HD.
Regina DeGraaff: I don’t think that that’s unfair. I think that’s a fact. [laughter]
Jordan Baker: That’s what I was gonna — go ahead and say that.
Regina DeGraaff: Yeah. [laughing]
Jeff Carroll: And then you have like all these other mutations which are obviously much less severe in their sort of implications and we — I mean everybody’s — once they have their genome sequenced — which mine’s online, you can go look at it if you want. Everyone else will have theirs soon and we’re gonna have to figure out how to deal with that.
Regina DeGraaff: Yeah. Yeah it’s —
Jeff Carroll: Were we talking about the movie? Sorry I got distracted.
Regina DeGraaff: Yeah, we were talking — well I was talking about like — so you have this documentary that followed your family eating dinner. Are there other instances in pop culture, in movies, in TV, in comics, I don’t know, in somewhere that kind of talks about either this disease specifically or any other kind of disease that has a good reputation of the neuroscience happening or a bad representation of the neuroscience happening?
Jeff Carroll: Yeah. So the one thing, the one person people used to know from Huntington’s disease was Woody Guthrie, like the great American folk singer from the like, “This land is your land, this land is my land.”
Regina DeGraaff: Yeah, I know that song.
Jordan Baker: Oh yeah.
Jeff Carroll: So Woody Guthrie, that wrote that, died of Huntington’s in the 70s and that was kind of the most — if anyone knew of Huntington’s, that was why. Bob Dylan wrote a song about him dying in a hospital and so that’s kind of the one connection people used to have. But subsequently, there’s been a lot more.
I always ask my students like, “Who’s heard of Huntington’s disease?” And like nowadays, they all raise their hands, and I’m like, “That’s weird.”
Jordan Baker: Thirteen.
Regina DeGraaff: They’re like —
Jeff Carroll: Yeah right, exactly. On House.
Regina DeGraaff: They read your Wikipedia page before they got into your class.
Jordan Baker: They already know.
Jeff Carroll: Yeah they probably did. So yeah that’s right. Thirteen, the character from House, had this whole big storyline of Huntington’s disease, right?
Jordan Baker: Yeah.
Regina DeGraaff: What? Wait you know a reference and I don’t?
Jordan Baker: That’s right.
Regina DeGraaff: Ugh, you win today.
Jordan Baker: Sometimes it doesn’t have to do with Star Trek. [laughter]
Regina DeGraaff: Was it on Star Trek, Jeff? [laughter]
Jeff Carroll: No. [laughter]
Regina DeGraaff: Ugh.
Jeff Carroll: It’s useless.
Regina DeGraaff: Useless. [laughing]
Jeff Carroll: But it was like a major storyline, right? Cause she went through the whole genetic testing. And it was a very bad representation cause the House part of it was a disaster, cause I think he like tested her without her knowledge or something?
Jordan Baker: Yeah.
Regina DeGraaff: What? You can’t test people without —
Jeff Carroll: Extremely not kosher but —
Regina DeGraaff: Unethical.
Jeff Carroll: People do it all the time actually, but that’s —
Regina DeGraaff: What? Wait what? What do you mean?
Jeff Carroll: The genetic test is pretty trivial technically, right? So if you wanna get it from a proper doctor, you have to go through all these counseling appointments and there’s like a protocol they’re at least supposed to follow. But a lot of people don’t want to do that, and there’s a lot of labs including — you know there’s a lot of labs in China that you can find on the internet that will like do whatever genetic test you want.
And there’s stories, like just stories I hear from the community about people who like test their kids cause they couldn’t handle not knowing or whatever. And it’s like, well you’re gonna have to handle it until they’re 18 and decide they wanna get tested. But yeah.
Regina DeGraaff: Wow.
Jeff Carroll: So it’s a tricky time because it’s technically trivial to test someone for this mutation.
Regina DeGraaff: Mm.
Jordan Baker: So you can’t test your kids, right?
Jeff Carroll: Yeah we did actually. So, and this is part of what the movie’s about. Our kids were prescreened when they were embryos. So we did a procedure called preimplantation genetic diagnosis, or PGD.
And what happens is that you go through a in-vitro fertilization cycle where they retrieve the eggs, and they have them in a dish, and they fertilize them in a dish, and they let them sit there til they’re eight cells, and then they take one of those cells, and they go and do a single cell test of the mutation on the fourth day.
Like, “Okay embryos one, two, and five are good to go.” And you have to make a snap decision. And Meegan and I, my wife and I, decided — I think we had two embryos that were unaffected and they were like, “Gotta do or die.” And so we were like, “Uh sure, plant them both.”
Regina DeGraaff: Yeah.
Jeff Carroll: And now we have twins! [laughter]
Regina DeGraaff: Yep!
Jordan Baker: Wow that’s —
Regina DeGraaff: And they do kickboxing with Tori.
Jeff Carroll: Yeah. [laughter]
One of them sort of does kickboxing. [laughter]
Regina DeGraaff: Yeah.
Jeff Carroll: Yeah and I forget about the HD thing. Like when they were embryos that was like all we thought about. Like, “Oh you’re gonna have kids that aren’t affected by this horrible disease,” and then they’re, you know, and then they’re kids and then you just — you’re just dealing with all the kid stuff and that’s kind of a full time gig, so.
Jordan Baker: Yeah.
Jeff Carroll: Yeah so we can do screening. You can also do — there’s other ways that are a little less crazy like the IVF thing. You can do prenatal screening. So you can wait until you’re X weeks pregnant and do amniocentesis and get enough DNA that way to do a test. That’s tricky cause you have to terminate the pregnancy if it’s positive which is, you know, that’s tricky question for people.
Regina DeGraaff: Right, absolutely.
Jordan Baker: Right. Yeah, yeah.
Jeff Carroll: Especially, it’s not like, you know, a fatal infant onset disease. It’s like, this person would be fine for 40 years or 50 years or something.
Regina DeGraaff: Exactly, and that’s a hard decision to make.
Jordan Baker: Right.
Jeff Carroll: Yeah.
Regina DeGraaff: Oof. But you did not have to make that decision
Jeff Carroll: No.
Regina DeGraaff: Because you — a forward thinker.
Jeff Carroll: Yeah. We often tell the kids they cost us $20,000, which they did. Luckily we got two of them, but we often tell them like, “You’re $10,000 in the hole,” because that’s how much it cost. [laughter]
Regina DeGraaff: You’re like, “You want that candy bar? You know you owe me $10,000!”
Jeff Carroll: $10,000. Yeah.
Regina DeGraaff: I can see them taking that really well.
Jeff Carroll: Yeah. No they — they’re like —
Jordan Baker: They’re probably good sports about it. Kickbox. [laughter]
Jeff Carroll: They’re pretty used to us ribboning them about it. For them, it’s very much just part of their world. They kinda know about it. But for like other kids who are from families that are less open about it, I think it gets to be this like deep, dark scary secret. And then that creates its own crap just cause nobody’s talking about anything that’s real.
And so, you know, maybe we err on the side of talking too much about it, but we just decided like — I don’t want that — you know, some of the worst parts of those things, those situations, are like just the fear and the like —
Regina DeGraaff: Yeah.
Jeff Carroll: And the hiding and —
Regina DeGraaff: And the anticipation.
Jeff Carroll: Right.
Jordan Baker: Yeah.
Regina DeGraaff: And that’s what I love about talking to you and actually even reading your Wikipedia page. You’re so open about that, it kind of takes away from my own neuroses of like hypochondria stuff. If we just like get it out there, you realize, “Oh, you know, we know about this stuff now so.”
And I wanted to bring up a couple things in TV and movies like, you have like beaches —
Jeff Carroll: Mm.
Regina DeGraaff: And you have like these stories about like, “Oh the mother died and then therefore, the daughter will die.”
Jeff Carroll: Right.
Regina DeGraaff: And like they don’t actually go into what that sickness is. It’s just this like weird, vague, “It’s something that’s genetic. People die.”
Jeff Carroll: Right. And that’s how it used to be. And now, you know, I meet kids and it’s cool. Cause now, a colleague and I from London do this website to inform patients and families about research news called — the website’s called HDBuzz.net.
So we write short, readable updates on current research findings. Cause you know, before that, it was like, “This thing cures Huntington’s,” and you have read the article to realize, “in a fruit fly,” like —
Regina DeGraaff: Yeah. [laughter]
Jordan Baker: Oh right.
Jeff Carroll: And like with a drug that will never make it into humans, you know? So we started it for that reason. And you know, I interact with a lot of kids, younger people that are consuming our content.
Like I go to a camp every year in Washington, DC, where a bunch of kids who are affected by HD come together and stuff. And these kids, like — they’re just growing up much more, just cause of the internet, and our site, and other people’s websites.
They’re getting a lot better information and they’re kinda like leap-frogging their parents. They’re just like, “Okay, this is this thing in my life and it sucks but I gotta just deal with it.”
Regina DeGraaff: Right.
Jeff Carroll: And you know, there’s consequences to testing and getting a positive result, but like, you can also plan your life better, and you know? That kinda stuff.
Regina DeGraaff: Right.
Jeff Carroll: Interestingly, when I was at that camp, you were asking about how rare it would be for Huntington’s people to meet each other.
When I was at that camp, I got a lot of questions about that as well and I could not put two and two together. And then I realized I was a camp full of like 18 to 22 year olds. [laughter]
Regina DeGraaff: And they’re like, “What if we had babies?”
Jeff Carroll: Basically.
Jordan Baker: That’s hilarious.
Jeff Carroll: “The only reason you’re here is to help us with our baby-making Issue.” [laughter]
That’s pretty awesome.
Regina DeGraaff: That is awesome. I think that’s a good place to stop. I want to thank you for coming and thank you for coming to the Spark Museum late at night, and talking with us about your work and this disease, and it’s just like the fascinating work that you’re doing.
Jeff Carroll: It’s cool. Thank you for having me.
Jordan Baker: Yeah thank you very much.
Jeff Carroll: Thanks guys.
Regina DeGraaff: This is Spark Science and we’ll be back again next week. Listen to us on 102.3 FM in Bellingham or kmre.org, streaming on Sundays at 5pm, Thursdays at noon, and Saturdays at 3pm.
If there’s a science idea you’re curious about, send us an email or post a message on our Facebook page, Spark Science. This is an all-volunteer run show, so if you wanna help us out, go to sparksciencenow.com and click on “Donate.”
Our producer is Regina DeGraaff. The engineer for today’s show is Natalie Moore. Our theme music is “Chemical Calisthenics” by Blackalicious and “Wondaland” by Janelle Monae.
[♪ Chemical Calisthenics by Blackalicious ♪]
♪ Lead, gold, tin, iron, platinum, zinc, when I rap you think
♪ Iodine nitrate activate
♪ Red geranium, the only difference is I transmit sound
♪ Balance was unbalanced then you add a little talent in
♪ Careful, careful with those ingredients
♪ They could explode and blow up if you drop them
♪ And they hit the ground
[End of podcast.]