Tosh Show - My Niece and Her Neuroscientist - Dr. Roy Sillitoe

Episode Date: March 24, 2026

Daniel welcomes his niece, who is affected by a rare neurological disorder, and Dr. Roy Sillitoe, a researcher who studies her condition. Support Dr. Roy's research http://giv.now/csc Support individuals and families affected by Hadley's condition https://www.pou4f1foundation.org/donate Join our Patreon for exclusive content: http://patreon.com/toshshow

Do you look around Texas and wonder if every other person you talk to has a genetic mutation? I do, actually. I'm always curious about, I think we all have mutations. We all have tons of mutations. Hang 10. It's Dan Tosh with Eddie Gosling. What's up, Dan Tosh? What you got for us today, big guy?

Sit back and enjoy it. You know what I'm doing right now? What are you doing? What you doing? I'm waiting for AI to take over. Hey, man. Go ahead, AI. What you're doing?

You're okay. Playing with fire. Go ahead, AI. See what you can do. Yeah, I don't see anything else. Nothing. AI thinks it's got me. No, it doesn't got me.

You got it. You think you don't need me. You need me. Ed? You don't need me. I need you, buddy. Oh, that's the nicest thing. Hey, I got a new chicken.

Okay. Okay. This breeder, I don't know if they're called a breeder, whatever. These people that we get chickens from somebody, they just reached out and said, hey, I got this Polish hen. They're not sexed yet, meaning they don't know if it's a rooster or a hen. But they're like, if you'd like it, they're yours. Well, I had to do a quick Google search, and I'm like, oh, my goodness.

That's beautiful. much like a what's your name who's the big golden girl yeah like a b arthur of the group i see that yeah like a little b arthur you got the little chickens and then you got this and i'm like yes so anyway they brought this polish hen over and she's big she's big now i know it's a she because she started laying but the other day i got an egg from her and i just couldn't wrap my head around it i'm like what is this. Hmm. I brought it in.

It's an egg. Now, you have to understand that these chickens lay small eggs to begin with. They're like this. This is like a normal egg that they lay. Okay. You know, it's covered. That's got poop on it. That's poop.

Nice. That's poop. Okay? That it's dried. You can scratch that poop off if you want. Is you flicking my way? There you go. Catch it.

But this egg, you know, you put two of those together and you're fine. You're good to go. It's a good egg. You know, some of them are bigger. than others. You know, their shapes, they're all covered in crap. You're getting the gist. I am. Okay? I'm going to keep those on my desk. All of a sudden, I get this egg. What? That looks like a piece of, like a candy egg. Oh, no. So I look it up when a new hand, like, sometimes it can happen when they get frightened. Okay. Or just like,

when they just are starting to lay, it's called a fart egg. A fart egg. A fart egg. Yeah, and usually fart eggs don't have a yolk. Now, I don't know. I haven't opened it yet. I'm dying to do it right now. Now, you know who loves eggs. Pete. Pete does.

Pete loves eggs. So guess what? I brought Pete in a whole slew of eggs today. This is from Tosh Farms? This is from my farm. Look at how much poop is on this egg, Pete. There's so much turds on these. Look at that one.

That one is just covered in shit. That was a tough get-out. Okay? That was a stubborn egg But look at this one Look at right here This one's beautiful That's a big egg

Yeah Next is a little fart egg A little fart egg So I'm dying to know Pete You want to put this in a little tiny Cup and pretend you're Rocky Yeah

You just drink this little fart egg How what can I put this fart egg in Here we've got a mug right here Yeah Okay Now normally you'd need two fart eggs To knock that's how you break eggs You like to break egg

Against the other egg That's how I like to crack egg You crack eggs on the rim? I do. I don't. Yeah, you can't do that. That's bad, Ed. I'll tell you why it's bad.

Flat surface. Because then you end up getting egg yolk on the back side of your pots and it just stains. It just doesn't look good. You should crack them together or a flat surface straight down. But I'm scared because I don't know if I can actually get my fingers into this and I don't want to lose whatever's in it. Right. So maybe I will try to crack it inside a little bit. What if, oh, what if something is...

Guess what? Hard as a rock. I didn't make any progress. Oh, there she is. Dry as a cucumber. Look at that. Now there's like a black. Oh, no, that's not the shell.

What is this? So inside, maybe it dried up because it's happened quite a few days ago. There's your map? No, but like, it's like, you see how it's... A baby? Can you see? It almost looks like glass. Oh.

Huh. Well, that's my first fart egg. But Pete, come get your loot. You just chew on this one, buddy. I think Pete should down all those eggs right now. You excited about all these eggs? How many eggs I give you there? That's more than a dozen.

Oh, you know what else? I got a new Mandarin tree. This is like the first harvest year. And I'm told on your first year, you're better off clipping all the fruit and letting it go. You're agreeing with me, right, John? Yes. So I clipped all my fruit. It wasn't mature. They're too sour. They're too small. But then it'll help it grow for next year. For sure. So here, I got about a couple thousand baby mandarin.

Are any of them edible? I don't know. Let's try it. Fart Mandarin. I'm not doing that. You guys are the tasters. But I thought that John would like this because he gave me those apples that were horrible. I thought maybe I could give him a bunch of mandarin's for his children to play with. At least if they dig their fingernails in there, their fingernails will smell nice. Okay. Here you go, John. This is for you.

This is for you. The bull sucks. So that's what's going on over there at Tosh Farms. It's a lot. It is a lot. You know how long it took me to do one tree of produce like that? How much? Like 15 minutes.

Then I went over to a lemon tree. I was going to do something similar. I was just going to harvest. And I always forget that lemon trees are made from the thorn of Jesus' crown. They're just straight knives that stick out. Yeah. Is that what they put on top of Jesus' head on the crucifix? Yeah, lemon thorns.

It's just a branch of lemons? Good. Gosh, lemon trees are pokey. It's almost like that's the forbidden fruit. Hey, is your hen laid any eggs since the fart egg? Yeah. Yeah, fine. They're all seem normal.

Great. Okay. The Polish hen is great. Speaking of eggs, we got some good eggs on today's show. You guys are going to get to meet one of the true joys of my family. My niece will be joining us who was born with an ultra-rare neurological disorder. And Lord knows she's had a go-thes. through a hundred times what any human should ever have to go through in life.

But she's, she's positive and she's happy and she's wonderful to be around. And thanks to brilliant minds like today's guest, new research promises to improve her quality of life and longevity. That's win-win. Enjoy. My guest today is by far. my favorite niece on my wife's side of the family. She's one in 276,66,66,66.6.6.6.6.6.

Repeating, of course. Literally. Please welcome Hadley. Thank you for being here. How are you doing today? Go. Okay. Ready for your first question? Yeah. Okay. Do you believe in ghost? Oh, no. You don't believe in ghost? No.

Good for you. So smart. Okay. Next question I ask all my guests. Are boys gross? No. No. Hmm. Is there someone interesting in your life? Yeah.

Yeah? Hadley, how old are you? Nine. Nineteen. No, not. What? Nine. Nine.

When is your birthday? November 4th. November 4th. And what do you want for your birthday? I'm a puppy to be. You just love puppies. Do you like your dog? Yeah, but it's like always Papa Doggy.

Betty, how old is Betty now? Vow. Do you like my pig potato? Yes. Are you scared of potato? No. Would you take potato home if I said you could have them? Yeah.

Okay, this is good to know. Because you know your parents, they'll get you anything you want. Like you start saying, hey, mom, I want a weird cat that's no one ever heard of. Next thing you know, you have this exotic cat. What is your cat's name? Sugar cookie Sugar cookie Do you go to school?

Yeah Is school hard? No Any cute boys in your class? Yeah There are? Yeah Interesting

Yeah Who do you like in your class? Um, Bodey Oh, Bodey Do you have a boyfriend? Yeah You do? Yeah

Oh man, is it serious? No Not yet, all right You were a big fan of Ed Sheeran Yeah What's your favorite Ed Shear and song? All of them. All of them?

Yeah. Oh, I mean, he's got a couple stinkers. They all sound the same. Is that what you meant to say? No. Okay. Hey, you got really good at swimming. Yeah?

Although yesterday you had a bit of a belly flop. There you go. But I'm less good in your pool. You're pretty good in my pool. Now, do we want to go surfing again? Yeah. The surf is pretty big right now. Can you be honest with me?

Who is your favorite uncle? Go ahead. Uncle Daniel. That's right. That's right. Do you hear that, Chase? Uncle Daniel. Okay, Hadley.

Do you have any questions for me? Go ahead. What is your kind of dog? What's my favorite kind of dog? Yeah. It's for me to own versus my favorite kind. I think my favorite dog might be a whipet. And they're like skinny little greyhounds.

They're the fastest. They're so fast. I think that's beautiful. But I also love an Australian shepherd. They're beautiful with a different colored eyes. I like that. You have pretty eyes. But, I mean, I kind of just like Carl.

Oh, eyes. You know, he's just a little, he's kind of a cuddly little Muppet. Yeah. Although he does eat my daughter's poop, and that's disgusting. Ew! I know. Everybody that's on my show gets a gift. Okay?

Okay. So I have to give you some gifts. You ready? Yeah. Yeah. Hold the little puppies. The first gift is this chicken. Now, this chicken was made by somebody from panda's life.

I think her aunt made her this chicken. But anyway, she put it in my airstream. I'm like, I don't want that chicken in there. I'm going to give it to Hadley. So here, you get that. Okay, put that on the floor. You're not going to. Then you can just drop it, Hadley.

Hadley, then you like to look at this photo all the time, don't you? Yeah. Yep, well, now it's your photo. And it's got my pig, my dogs, my chickens all in it, wearing birthday hats. Okay, you get that now. You can throw it on the floor. Don't worry about it. Now, this gift, it's probably more for your mom, but you can use it with her.

Because the people, when I do my shows at the Cosmopolitan in Las Vegas, there's the free plug. I steal all the bathroom products. And your mom happens to like the bathroom products that are there. So I'm just going to give them to you. and then you can pass them on your mom. Oh, yeah, she's going to love them. She's going to love them. Oh, you're going to love them.

And you can use them, too. Make your hair smelled a lot. How often do you wash your hair? Life times. Five, that's a lot. Probably too much, to be honest with you. You might be drying it out. Anyway, this product, so these are, this is really good.

What does this go? Orby? Oh, yeah, it's expensive stuff. Oh, do you ever, do you ever wear a face mask? No. Oh, your skin looks lovely. You could try these. They have face masks, too.

This is great. do you think of all this? We're just going to push this all over there. You know the drill. Throw it to the floor, Hadley. Just do it, Hadley. Just do it. Throw it. All of it. There we go. Oh, it's perfect, Hadley. Thank you for respecting the desk. I have one more gift for you. Now, you know, uh, Panda. Yeah. You know her brother. John John? He was in Mexico. He got a hand job from a masseuse. I don't even want to go into that. Yeah, yeah, yeah. Okay, okay. He always buys me gifts. I always end up giving him away. Anyway, he bought me a pair of shoes, and guess what?

Yeah. I loved him. I loved him. I go, perfect. I love pink. I think pink and like a blue. Anyway, I grab them. I see that they're 12s.

I try to put it on. It doesn't even, I go, this doesn't look right. And it doesn't fit. It doesn't fit at all. It was like a women's 12 in a different country or something. I don't know. Anyway, the only man I know that has feet small enough. to fit these is your father.

I'm so excited to give them to you. You can give them to your dad. Okay? Oh, he's going to love them. They're great. Look at these. Do you think your dad will like those shoes? Yeah.

Again, I don't understand. I mean, those aren't 12s. Oh, man. What size of your dad? We're a seven, seven and a half? It's not, it doesn't matter. Anyway, you give these to your father. You tell them, good luck beating me in pig wild.

It says right there, look, says size 12. It's not a 12. I don't know if it's women's or what, but whatever. Anyway, give those to your father. Thanks for putting it on the floor. You're welcome. You're welcome. We'll be right back.

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Dan, 64,000. Message and data rates may apply. See terms for details. My guest today is a world-renowned scientist, researcher, and professor who has dedicated his life to discovering the origins of neurological diseases. so prepare yourself for an hour of me asking questions I know little about. His work is particularly important to me because his expertise includes the rare condition that affects my nine-year-old niece.

Please welcome all the way from Texas via Manhattan, Oxford, Calgary, Zambia, Dr. Roy Sillito. Thank you very much, Daniel. Pleasure to be here. That's a mouthful. It is. It's been a mouthful getting to all these places. I mean, had you gone the other direction, I would think, oh, job well done. But to end in Houston, how upset is your wife?

Well, you know, she's been very supportive, but I can say a few places we've left that's been tough leaving Vancouver was very difficult. I mean, beautiful. I know. That's a tough one. Are you kidding? Did you ever go up to Whistler? Oh, we did. Yeah, absolutely.

It's just delightful. Yes, it's amazing. I went skiing once. Uh-huh. I'm kind of an embarrassment for anybody that grew up in Canada that actually don't know how to ski. Can you ice skate? I'm not bad. I'm okay.

Let me tell you something. You're a large man. I don't think it's a good idea that you ice skate, to be honest with you. We had to, so part of growing up in Canada is that, you know, P.E., you get to play hockey. And so that was my introduction to ice hockey was in P.E. So sort of could skate, and I did my best, but it was not pretty, but I tried. You're too smart for this, of course, but a bruiser, you know, a guy in ice hockey that just comes out to fight people. Right.

That could have been your role. It could have been. But in high school, I was kind of a mommy's. boy, so might need my mom to back me up. All right, here I go. First question, do you believe in ghosts? I believe there's something out there. Things are too creepy that there's nothing out there.

We all get that feeling, and I don't think it's all in my head. So I think there's something. I don't like knowing that there's a lot of stuff going on in your head. That scares me. When did you move to Canada? How old were you? I was 12 years old when I moved to Canada. From Africa, how was that transition?

It was rough. It was a big deal, actually. So my two older brothers were there. One was 16, the other was 18 at the time. And you were 12? I was 12. My dad and mom's vision was to get us out of Africa, to get us in education. I mean, they still lived in Africa.

They still do. My mom does. It's one of those other beautiful places that it's hard to imagine we left. But education, this was in the 80s, was the primary goal to get a better education. So I followed up my brothers who were in Vancouver. Yeah, so you lived with your brothers as they became, you know, the head of the household. Yes. How did that work out?

I got to give my dad credit for quick thinking. And, you know, in Africa, there's kind of no rules, right? So that would be perfectly fine in Africa. But after we got there, my dad discovered that nobody would actually rent an apartment to three teenage boys. Go figure. So my dad actually offered a very nice couple. He said, I'll give you cash for a year. How does that sound?

They said, I'm sure your boys are so fantastic and very responsible. So we looked after each other. That's not legal, though, right? There's no, not forget the apartment thing. You can't just have three people leave a country and live somewhere else before they're 18. So my brother was actually, could be my legal guardian. Huh? Yep.

Oh, if my sister was my legal guardian, my life would have turned out so different. All right, before we start with the reason you were here, your grandfather helped start the MI5 in England. Did your grandfather know Jackson Lamb? So first it's my great-grandfather. Great grandfather started the MI5. He did, yes. He was part of the group that started. Well, he was the head of the MI5.

He was first desk? Well, so the story goes that he was a law enforcement officer and pretty strict guy, and he was grumpy writing out Ministry of Information Room No. 5. And so he decided, we're calling it the MI5. The office was there, of course, but he coined the MI5. Was your great grandfather James Bond? Well, he was the real life James Bond. It was written after him.

So, of course, he was a British soldier at the time, and he had gone to Africa during the war and had one son in Africa. And when the war ended, he wanted to come back. He missed Africa. And he knew he had a family. Apparently, the story goes, he was trying to take every opportunity to go back. So when De Beers Diamond Company came calling to help solve the diamond smuggling, because at the time, he had now retired from the MI5.

They figured he would be the man for the job. and he jumped at it, partially because of the challenge, but the other part was to get back to Africa. And the story is that Ian Fleming caught wind of kind of this story, and he kind of adapted it. It sounded, you know, sexy in his mind. And it was, it was an amazing story. So he is the real life James Bond.

What kind of car did he drive? I actually don't know, probably a very cheap car given by law enforcement. You're the smartest person we've interviewed, And we've spoken to tons of people from Stanford. Explain to me as if I'm a fourth grader, what your job involves. So my primary job is research and I study the brain. I'm trying to figure out how the brain forms, how all its different connections make the brain that you have,

that gives you the ability to move, to think, to feel. And particularly, I'm interested in not only how it forms, but once it forms, how does it start to work? how are we able to do all the wonderful things that we do as human beings? And that is really the basis of what we're trying to figure out. Over the last 15 years, my thoughts have really changed from not only thinking about how does the brain form and function, but what happens when it doesn't? What are the problems that arise?

And so I've really focused my career and will focus the rest of my career in understanding brain diseases. How many problems can one gene mutation cause? One gene mutation can cause several. There's many cases where, you know, you have monogenic problems in one gene and one mutation. Those tend to be, dare I say, the simpler problems because we can track them a little easier. But there's many cases where a single gene can have multiple problems. One is a good case, a good example of a gene which causes cerebellar problems.

And this gene, if there's a mutation, it will cause a severe problem called ataxia, which is when you cannot coordinate your movements. but a different mutation in the same gene can cause epilepsy and, you know, it's dramatically different. And very interesting and really intriguing, a third mutation in that gene can cause migraines. So seemingly very different problems, one gene. Can there be good mutations?

I mean, I don't know what good is, but like can some gene mutations be that causes something extraordinary in the positive? I don't think so. I don't have any evidence, at least from the cerebellum, where, you know, there's one problem that is causes a dysfunction and a second one resolves it in some way. I'm not aware of that.

I used to get migraines. And then not often, once a year. And then one year, 17 years ago, I never had another one. And I never did anything. Why'd that happen? You know, I actually have a similar story. I grew up with a ton of headache problems as a kid. And I never got them diagnosed as migraines, but they were bad.

I mean, I'd black out. I'd black out, I'd vomit. Yes, me too. Absolutely terrible. When I left Africa, they stopped. Age is one thing. In terms of migraines, there's so much going on. It's not only a neuro problem, but there's issues with the blood, the vascular, there's issues

with pressure is another one, depending on where you live. So it could be where you actually moved during your life. It would have actually impacted that. Wasn't that, okay? It was something, but it just stopped. What is a cerebellum? And who has one? The cerebellum is just the coolest part of the brain.

Oh. This is what I work on. I think it's an obsession now because it's what I love to talk about. It's what I dream about. You dream about that? I dream about the cerebellum. I dream about experiments. I'm sorry.

I dream about experiments. Such a nerd. And, you know, half the experiments that I've worked in my lab actually came from dreams. Oh, I don't know if I like to hear that. No, I know, but it's you, they keep going and going. I guess I've let the cat out of the bag for all my students when they say, Roy came up with a crazy idea. I didn't come up with the crazy idea. I dreamt about it. Okay. Dystonia, what is it? Distonia is now considered the third most common movement disease. It's a severe condition.

It doesn't typically cause any intellectual problems, but its movement is one of the key problems. It's very common because it can be, it can exist with a lot of other common disorders that people talk about like Parkinson's disease, seizures, and any of the other cerebellar-based diseases, what happens in dystonia is that if you and I try to, for example, flex your arm, the bicep has to contract and your tricep has to relax. And that gives you the ability to move your arm. In dystonia, both muscles contract at the same time. And it contracts and it's uncontrollable. The problem is that that can happen to any muscle in the body. They can imagine any muscles in your neck, in your face, in your back, it's excruciating, especially for children. That prevents you

from eating, from speaking, from doing anything that you'd normally do on a daily basis. It's a huge problem, dystonia. Ed, you remember that a cheerleader for Washington? Right, she can walk back. Yeah, let me, I think it was proven that she was a faking dystonia, wasn't it, or no? Could be. I don't, there was this one where she, do you know who I'm talking about? I know who you're talking about. Her movements were herky, jerky, and all over the things. but she could walk backwards fine. Not that this is important, but she was a smoke show. So she's this hot girl that is normal when she walked backwards,

but when she walked forward, the dystonia would go all over the place. Right. But I didn't know that it was real. It is real. No, I didn't know that her case was real. I thought she was called out. So she was called out, and I did watch the video. Uh-huh.

And you said yes or no. Well, it looks real. It looks real. But, you know, I've never spoken to her to actually see whether. Okay. Was real. Did you learn about the video from our show, Tosh Point O? Oh, man.

I don't know where I heard about it. I feel like we launched that. All right, you discovered a gene for dystonia and created it in a mouse and were eventually able to normalize the mouse's condition by electric stimulation to the right region of the cerebellum. Mice seemed to be the go-to animal when testing eventual cures for humans. Is that why we like cheese so much? It very well could be.

We all have a little bit of mouse in us, I'm sure. What's your mice budget? It's actually shockingly high. No, I believe you. I probably spend about $75,000 a year on mice, which is a lot. No, I mean, I know. But you did. You gave a mice dystonia.

So what we did, we had been studying several different genes that we knew caused dystonia and human. The problem is that, and this is true for many conditions. once we put these mutations in mice, they don't always show the exact same problem that we see in people. In many cases, they do, but for dystonia has been problematic. So what we decided, we said, okay, take a break from just mutating the genes,

putting them in mouse, looking for dystonia. Let's actually ask, what are we actually trying to solve? And it was the neural problems. It was the functional problem that is caused by those mutations. So we said, let's create a different set of mutations but block the brain from communicating properly. And we directed the mutation to the cerebellum.

And we created a very severe dystonia in mice. This gave us the opportunity now. We had a mouse with a very severe dystonia. We knew what the problem was. We knew the cells that were dysfunctional. So this to me was almost the perfect tool to start to ask, how do we solve this problem? So we started stimulating regions of the cerebellum

to resolve it and reverse. the movement problems that we induce. And by stimuli, is it just electrocuting? What are you doing? Yes, great question. So we actually miniaturized what is used in human Parkinson's disease, human dystonia, human epilepsy. It's a surgical therapy called deep brain stimulation.

In this case, it is an electrode you put in the brain, and you use a tiny current. So it is absolutely electrical stimulation. And how long will that last? So you can... Reprogram the brain? Yeah, so that's one of the ideas we'd love to do. Typically, in your typical deep brain stimulation, you don't reprogram anything.

You turn it on. You can turn it off. In some cases, it's chronic. It stays on in Parkinson's disease. The person has kind of a controller that's implanted in the chest and you can turn it off. Once you turn it off, you go back to having the symptoms. So you bring up a great point. The hurdle we've been facing in the lab is that we've been able to apply the debrain stimulation

in mice for a test. for dysonia, for tremor, and it works fantastically well. And some of our procedures, we've worked with neurosurgeons, some colleagues have adapted our protocol, and it works in people as well. The big hurdle is that once you stop stimulating, you go back to having all the symptoms. And we've been asking ourselves, well, how do we make it last? How do we make this procedure fix the brain for good, if you will? And so we have some new data showing that if we, what we call it, we call it closed loop. we use the brain's own signals to start the deep brain stimulation

and once things go back to normal it stops when he goes back to being abnormal the deep brain stimulation kicks in again so we're essentially using the brain to teach itself it's like a generator for when the electricity goes out yeah so it absolutely is yes that's better than what I would have come up but I would have just turned the knob a little more

turn it up give them a little more juice see what happens this time mice Do you look around Texas and wonder if every other person you talk to has a genetic mutation? I do, actually. I'm always curious about, I think we all have mutations. We all have tons of mutations. Okay. It may just be, it is just many of us don't realize it because it doesn't impact our lives.

But our genomes are full of mutations. And for the unlucky people, it manifests as something that we see as, you know, in my case, a back problem or even worse. cases is a genetic disorder. How did you come to know my niece? That's an interesting story. I was friends. This is a colleague. I had met him. We were both postdoctoral fellows. And he was studying a gene that was expressed in the cerebellum. And we had talked for many, many years about working together. He used to work on the retina. And by chance, this gene was expressed in the cerebellar system. And he wasn't super interested in cerebellum. Say, oh, you should use this. I think you could tell you something. And I looked at his data. That's what I think they'd be talking about. Okay.

And so we kind of kept this up for 20 years. During the pandemic, he reached out to me, and he had moved back to Europe to continue his work in his lab there. And he said, you know, I've been working on this, and it turns out there's a mutation in this gene. And there's kids who have these mutations. And he had been in touch with several people, several clinicians, and he came across your family as well. And so we started chatting. And starting to think, well, you know, this wasn't just, again, as a scientist, sometimes we find something that looks interesting. And then it turns out that it's super important for people's lives, if there's a mutation.

And that's where we started to discuss, well, how many people have this mutation? What does the mutation look like? Do they have cerebellar problems? And it turns out that, yes, this is a cerebellar problem, that these kids have ataxia. They have speech issues. So this is how I've come to now learn more about this mutation. How rare is her mutation? It's very rare.

So far, I think there's only about 30 kids that have been identified with this mutation. So this is very rare. But the problem with rare diseases is that once somebody is identified and the population grows, there are many kids and potentially adults around the world will have similar mutations. We just didn't know this is what they had. And as you mentioned before, the different mutations in a gene, you may have one variant of this. mutation is mild, another variant is more severe. And the person with a mild mutation may never actually be discovered. Explain what POU 4F1 is and if it is also your license plate.

No, it's not my license plate. It sounds like a confirmation code. Is this have a fun name or is it just POU4F1? It's got a fun name. So the genes are named for where they're expressed and in this case it's what the region that it's in actually does as a protein. Got it. Right? Sometimes they're not fun names. They have a bunch of numbers in them because it's the position. But in this case, this gene, there's other family members as well of the gene, which is why there's several numbers.

That's just the specific one? Yes. That she has to deal? Yes. All right. I mean, I don't know if it's a high priority, but could we rename it? Anybody? Yes.

Tosh Titus? There's nomenclature committees out there. They love naming genes. What is causing Hadley's symptoms? From what I understand, a lot of them would be caused by cerebellar problems, particularly here any motor issues, speech issues, for sure, are driven heavily by cerebellum. Is she trapped in her? Like, is she comprehending way more than she's able to express?

That's a great question. And so if it's affecting predominantly motor problems, then yes. The intellectual ability is heavily intact. It's exactly as you say, it's expressing that is a big problem. Is that torture? It's frustrating for kids and adults with that. It's absolutely frustrating. Well, how are you trying to treat her mutation?

For the developmental mutations, this is particularly tricky. Because what happens here is that she's had the mutation growing up. So her brain has developed without the gene functioning normally. So connections and everything she does is how she's formed. There is a possibility that one could think about procedures like deep brain stimulation. What are the issues that bother her most? And are there brain regions, for example, the cerebellum and its connections, that if we stimulate, can restore functions to a point that it helps her quality of life?

We need to collaborate better to solve these problems. To solve a genetic mutation like your niece, we need to have pediatric people, we need to have neurosurgeons, we should have neurologists, we should have the basic scientists who are interested in developmental biology, neuroscience, genetics. You need an entire team to tackle these problems.

I mean, the nightmare of, I'm sure the list is endless, but when you have a child that needs extreme care and hospitals talking to other hospitals, that nightmare of, you know, you're basically handcuffed for the rest of your life of like, I'm never going to live in the bush in Africa. I have to be by this specific hospital or I have no shot. Yeah. Does Stephanie, my sister-in-law, have your cell phone number?

Yes. Oh, man. Does she send you long texts? Uh, yes. Where, like, you need a medical degree to fucking understand them? You know, I appreciate them because I'm still, no, because... You can understand them. Like, I'm just trying to get highlights and maybe some cool picks.

I'm from the generation that uses proper punctuation and grammar in text. So when I get a nice long text, it's like an email, which I love. Yeah, no, that's not me. I'm writing like a child still. I refuse to capitalize. Do you fuck with a medulla oblongata? I do, a lot, actually. Well, POU for F1 does have expression in the medulla oblongata,

and it's that connection to the cerebellum that is problematic. You mentioned millions of people have cerebellum issues and that it's linked to everything from autism to sleep disorders to alcoholism. Yep. Dylan back there, his cerebellum, I don't know if you need to look at it. The guy drinks just constantly, almost doesn't affect them. Is that something we should worry about? It's not a good thing. Okay.

So it's not good. So of all the brain regions, the cerebellum is probably the most sensitive to alcohol. Do you drink alcohol at all? I do. I do. And I suffer the consequences, too, of after a couple of drinks, your balance goes, your precision goes. That's cerebellum. Is there a part of the brain you could touch with electrodes that would make Eddie and I better at spelling?

Probably. I would guess there is. Oh, wow. You know, I think it would still take a bit of practice? You ever see that John Travolta movie where he got struck by lightning and for like Phenomenon? Phenomenin, that's my favorite movie. Oh, you like that. I absolutely love that movie.

He was just smart for like a month or something like that. And then he died. Listen, that's a lot of electricity hitting his brain. You're not going to live for a long time with that much juice. Absolutely love that movie. Yeah, it's so funny. Is AI going to be able to map out the brain soon so that, you know, you can be like, okay, this is where we need to target?

Yeah, it's a hot topic. I mean, everybody is using AI. I think there's a lot of promise in it. The big problem right now is that there's still a lot of information. to put into the AI. Let's talk about the human brain. I say, you know, we study mice predominantly, but we also study human pathology.

A few years ago when I started to really dig in to the human cerebellum and human pathology, even after 30 years of studying the structure, I realized how much I didn't know. And so my kind of question now for AI is how good can AI get if we don't actually know what the major components are in the nervous system?

And maybe AI figures it out. There's a lot of promise, but who knows? I'm not doing it. It's not for me. How crucial is funding to your work? Without the funding, I don't have a job. My day is filled with trying to get funding. My own salary is self-generated as a researcher.

Anybody I get in the lab, my graduate students, post-doctoral's, technicians. Mice. Of course, mice. Those part of the tools. And then anything else we do, part of the experiments, publications of the papers, going to conferences. and we also have to help support the schools that we're in. Without the funding, there is no science.

The schools can't cut the big checks? They do. I mean, the schools work hard to raise a lot of funds. They do help. But it takes us all. The way the institutes run, it has to be as a team. When you specialize in such rare conditions, is it harder to get funding? Yeah, it is much harder.

I mean, because if you would focus on hair loss, right, the money just pours in. I'd be my first client. Well, but no, you raise an important point because it's, you know, I don't want to downplay the importance of any of the big diseases that we tackle with tons of money, like cancer, is one of them. Rightfully so. The money that has been put into cancer should be. There should be more money in cancer.

I wish for the rare diseases, we could also do that. But partially, it's a numbers game. If only few people are affected and there's only so many resources to go around, And it's understandable in one way that a lot of the resources go to what is affecting millions and millions of people. How can people help with funding for your research? Do you have an only fans page? I do not. But we do have a site that we've created where people can support us.

I mean, that's what we should be plugging. Instead of trying to sell T-shirts that have Carl's face on it over here. Do some good. For more information or ways to donate to the research, visit G.I. We'll be right back. You don't need a personal trainer to get the results you want. All you need for a personalized workout is FitBod. FitBod creates a personalized workout routine based on your goals, fitness levels, and

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How's it going over there, Pete? You still using it? We're still using FitBod. We're in Month 2 with the app. You're in month 2? Oh, yeah. Wow. Level up your workout.

Join FitBod today to get your personalized workout plan. Get 25% off your subscription or try the app free for seven days at FitBod. slash tosh. That's F-I-T-B-O-D dot M-E-slash-T-T-Sh. What do you need a year to make things like, oh, now we're cooking? For me, right now my lab probably needs about half a million to a million per year. Seems totally obtainable. And that's...

Ed. Yeah. It is obtainable. And I think that's where we have to spend a ton of our time doing the work. But your question is, is... If things were rolling, let's say we need to solve the big problems. I say we need three, four, five times that. Because at the pace we're going, we're finding a lot of interesting stuff about the brain,

about biology, about us as human beings. We are identifying disorders, finding genetic mutations. The question we have with the problem, the hurdle, we need to find cures. Well, how soon are you to actually trying to stimulate like a human brain? Have you done it? So we have many colleagues that are doing it. For cerebellum, that's just starting now, but it's very slow to get to that point. You also, I mean, besides the things you mentioned, he also said, like, posture is one.

Yeah. Because here's what I'm telling you. I'll pay you right now at least two years' worth of research if you go into my wife's brain and fix her posture. Because the writing's on the wall. I've seen her family. She's going to turn into this hunchback. And it disturbs. Listen, I love her.

Don't get me wrong, but at 80, I'm not going to like it. It's going to, and I'll sign any waiver that says, I don't care what you do. Just go ahead and start poking. There's many spots I can think of that might help the posture. I'm not sure about the hunchback, but. Well, I mean, it's just going to be there eventually. If you could just go in, zap her a couple times, listen, if she changes personality, that's a twofer. I'll take it.

What do you do to unwind? You have any pastime? Not really. Honestly, I go to the gym, hang out with the kids. So for the last 18 years, it's been cerebellum kids, cerebellum kids. My son's going to go off to college next year, so we'll have a little more time. Maybe then I'll discover actually of some interests in the world. You work out like a crazy person? It's early. It's crazy early. But what time? What time do you get up? I get up at 4 a.m. How off? What time do you go to bed? 10.30? Guess what? I'm going to give you some advice. Okay.

You need a little more sleep. I know. A little more sleep. That's not ideal. 10.30 to 4.30? No. You need a little bit more. It's not horrible.

Unwinding is hanging out with my wife and kids. Do your kids work out? My son started about a year ago. He's always been in sports, but he's never actually worked out until this last year. Do you do everything with health? Because physical is a big part of this as well. Yeah. So what do you mean by everything?

No, I don't know. You watch everything that goes into your body. food-wise? Do you take, you know, supplements? So about three years ago, you know, like a lot of other guys, you think, oh, I'm doing great. I'm good. You know, I wasn't keeping up with doctor's appointments as I should until I went to the doctor. I mean, he says, your cholesterol is bad. He says, either do something or you're going to die. And I thought, geez, I kind of feel good. But cholesterol problems are one of those issues that, you know, you need a test to look at it. So I had to actually change my eating. So I had to for the first time actually watch what I'm eating and try to be good.

It's really tough in Texas because the food is so good and it's so bad for you. Yeah. But I try. I try to eat better. I brought my cholesterol down. That's when I went back to the gym despite having the back problems. So I just try to be really careful. That's why, as you said, do I work out like a crazy person? Not really. I mean, I try to lift an exercise in an age-appropriate way. You do cardio? Yeah, I run every morning as well. So when I wake up, turn on the coffee, go running. It helps with the cholesterol. I don't like running.

I'm too big to run. No. You ever tinker around with your own kids' brains? I used to kind of feel behind the heads, you know, pretending that I could feel and massage the cerebellum. It may have helped, but I definitely did. I wonder what's in there. Where are you on parents being able to choose their child's features, like eye, hair color, height, weight, sex? I think that's crazy.

That's crazy. I don't know if we can get there. I think that's a tough one. Everybody that's on the show gets a gift. It's just stuff around my house. You live in Texas and you have a PhD, so here's a putter. Do you golf? I've never golfed, but I will now.

No, but this putter right there is a former PGA player, Mickey DeMorat. He is my nephew. He was on the Pia. He used that for a bit. Wow. Thank you. Thank you. I don't know why I have this, but it's for your wife or your daughter.

They put jewelry in it or something like that. It's just, I just don't want it in my house. I'll put it in mine. Thank you. That's how the game works. Look at it. Put it on the floor right away. Thank you.

Talk about your family's hatred for the late, great Kobe Bryant. Oh, no, we love Kobe Bryant. Oh, you do? We just don't like black mambas. You don't like black mambas. My bad. That's bad intel. Are you, so you...

Kobe Bryant's amazing. You're fine with Kobe. You hate black mambas. Yeah, we don't like black mambas in my family. My dad's youngest brother was killed by a black mamba. What's... Can you do anything? How long do you have?

You don't have much time. You have minutes. And you don't feel their bites as much because their teeth are so thin. That's right. And then they strike several times. On every strike, you'll have multiple penetrations. What are you supposed to do? Are you supposed to just not play as a child?

I mean, that's living in the bush in Africa. You know, there's snows. snakes, lions, elephants. That's how it is living up there. Well, I mean, I'll tell you what, that's a pretty big strike. Yeah. I mean, the story is if you see a black member, where you're not going to tell the story about it.

I don't like that. Describe your dream scenario of what this electric stimulation technology will be able to do in 10, 20 years. Right now, we're at a point that we've got a platform where we can train the cerebellum to almost fix itself. And we've done several studies now, and we've applied for a patent, which is very exciting, that after we stop stimulating,

the mice actually continue to do very well, and these are mice with dystonia. They show almost no signs of dystonia after three months without stimulation. So this is a case where we've created the dystonia by blocking communication. The next point is how do we take, the stimulation and pair it with a gene therapy. That for me is going to be the dream. How do we fix the brain communication, but actually how do we also fix the genetics and the molecular pathways? I think they all have to go together to actually reverse all of the symptoms that we want to

reverse. That for me is going to be the dream scenario. And on top of that, have it completely non-invasive. So you walk into a clinic, you have some kind of stimulation, some kind of kind of therapy that actually fixes your brain communication, activate certain genes, dampens the bad genes, and you walk out. And that's obtainable in 10 years, 20 years? 20 years, maybe, at least. For the brain stimulation part, for sure. There's a lot of non-invasive techniques coming on.

For the genetics and molecular, that's partially me dreaming. Okay. This one's for Eddie. I'll give Eddie one. Could Jesus's DNA be extruded from the shroud of Turin? and then could that DNA be used in a lab to bring about the second coming of Christ? Eddie has had a theory on this for many years. I'm pitching rat Jesus.

If we could create a Jesus duplicate in a rat, that would be... You know, it's wild, but that is actually a trivial experiment to do. That is very possible. It's scary enough. You get some funny in Texas. You start creating rat Jesus. There we go. We're in.

Thank you for being here. Dr. Roy Sillito. Sillito. Thank you. That's your last name? That is my last name. I didn't even have a question about that. Your parents are, how do I put it?

Florida well-to-do. How much money does your dad actually make? You know how much money he gets paid? No. You don't? No. Do you like Kiowa? Kiowa, yeah.

You guys love to go there. Heading up to South Carolina. You guys got to come. It's like other places. How are you feeling right now? How's your health? When's the last time you were sick? Three years.

Three years. Three years since you were in the hospital? Yeah. I mean, this is like record stress. What is magic medicine? That helps me. It helps you? Yeah.

Uh-huh. Magic medicine is what old Dr. Roy is working on? Yeah. Yeah. Okay, Hadley. Thank you for being on my show. You're welcome. All right, have a good day.

Let's go surfing. Oh, this was some fancy bracelets you got. A puppy duck. Oh, is a doggy? Yeah. I had a duck once. Wow. My mom bought me a duck.

And then I was like, we had it in a thing in the backyard. And then, like, it just immediately flew away or was eaten. I don't know. Just left. I was like, I'm not going to stay here in this tiny little thing. Didn't have a roof or it. It was a bad gift. Want to thank Hadley and Dr. Roy for being on the show.

And my brother-in-law, so excited that he got a pair of shoes. That's right. Because his size has never lined up with my hand-me-downs. So what a treat for him today. You're sad because Hadley's leaving. Nobody gives you more love than she does. Yeah. Well, we'll have to go to Florida, which I know.

puts all of us into a slight depression. But that's what we got to do. Gotta go see the family. Let's do some plugs. Patreon.com slash toss show for some extra content. The stuff that is too hot for the internet. My first farewell tour. Tickets are on sale now.

We're heading out this week, Ed. We're going. Oh, we got so many pizza spots to hit up in Indiana. Who knew Indiana was so full of pizza spots? Are your buddy going to be at the show? I think he told me he's already got tickets to two shows in the Midwest. Two? Two.

You only need to get tickets to one show and then just remember the material. Yeah. Oh, boy. Well, the pressure is on. I cannot. There's no pressure on me. Measures on you and your buddy Hutch. Hutch.

Maybe he'll join us for one of these pizzas. I'll buy Hutch a slice I'm not going to get him a whole pizza Get him a whole pizza and we just leave He sits there with a whole pizza No I'm not giving him a hole He can have a slice Slice I'm excited

I've been hearing about that stromboli pizza It just seems like a pizza folded up right No, it's got to be something special It's got to be But I don't think it is All right Who knows, we'll try it Toshoshostore.com

Get some merch And now hit the music For they love me They love me not This is where Eddie reads some comments, one positive, one negative. We have to figure out which is which. All right, what's the first one you got, Eddie? Here we go.

This is from Elizabeth Gleeton 1598. Oh, Elizabeth. Yeah, thanks also to Daniel Tosh for highlighting non-celebrities who do important work and jobs. Well, you're welcome. I appreciate your comment. There you go. Okay? That obviously is they love me.

Even though that one just seemed more kind of like they appreciate me, which is a different segment. Okay? I wanted like they love me. I want to see like, oh. Yeah. Something a little thicker. Oh, yeah. Bring it.

Bring it, commenters. All right, here's the other one. Next one? You should know better V2. First time I gave up on a Tosh show interview. I just can't do it. Oh, they didn't like the interview. And they, well, what show was that from that?

That's an important piece of the information here. Yeah, I don't have that. I should have, you're going to find that. I mean, because that could have been from our travel agent. A lot of people felt the same way. Right. But if that was for my wife, you know, what am I to do? Mm-hmm.

I live with the person. I love the person. Yep. And now I got to be like, I got to get rid of her? We don't even know what you want to go back and look at to take the notes and see what we could do better. Well, the good thing is next week, it'll be somebody new sitting across from me. See you next week.