My Niece and Her Neuroscientist - Dr. Roy Sillitoe

Summary

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Tosh Show – “My Niece and Her Neuroscientist – Dr. Roy Sillitoe”

Date: March 24, 2026
Host: Daniel Tosh
Guests: Dr. Roy Sillitoe (neuroscientist), Hadley (Daniel’s niece), Eddie Gosling (co-host)

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Episode Overview

This episode of the Tosh Show takes a deeply personal turn as Daniel Tosh introduces his nine-year-old niece, Hadley, who is living with an ultra-rare neurological disorder. The heart of the episode is Tosh’s conversation with Dr. Roy Sillitoe, a world-renowned neuroscientist whose research directly impacts patients like Hadley. The conversation balances Tosh’s signature irreverence with moving humanity, exploring gene mutations, dystonia, brain research, and the challenges of rare disease funding—with an undercurrent of humor and optimism. The episode spotlights the realities of families dealing with rare disorders, scientific innovation, and the critical need for collaborative research.

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Key Discussion Points & Insights

1. Family Context and Personal Stakes

• Daniel introduces Hadley, describing her as “positive and happy and wonderful to be around,” despite her rare neurological disorder.
• Hadley, age 9, enjoys pets, Ed Sheeran, and school, and she’s candid and charming with her uncle.
• Tosh explains his personal investment, noting that new research could improve Hadley’s “quality of life and longevity.” (08:17)

2. Meet Dr. Roy Sillitoe: The Scientist with a Mission

• Dr. Sillitoe’s background includes global moves (Africa → Canada → Texas), a family history tied to MI5, and a focus on rare neurological disorders.
• Quote: “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.” (24:30)

3. Explaining the Science: Gene Mutations, Cerebellum, and Disease

• Gene Mutations:
  • Single gene mutations can have multiple, dramatically different outcomes (ataxia, epilepsy, migraines). (25:15)
  • Most mutations are harmful, rather than conferring special abilities.
• Cerebellum:
  • Dr. Sillitoe is passionate about the cerebellum, calling it “the coolest part of the brain” and revealing that many of his research inspirations come from dreams. (27:20, 27:36)
• Dystonia:
  • Defined as the third most common movement disorder, involving severe, uncontrollable muscle contractions that can be excruciating, especially for children.
  • “In dystonia, both muscles contract at the same time, and it contracts and it’s uncontrollable… It’s excruciating, especially for children.” (27:56)

4. From Mice to Humans: Innovations & Hurdles

• Dr. Sillitoe’s lab created mouse models of dystonia to test treatments, spending about $75,000/year on mice alone. (30:17)
• The big innovation: using deep brain stimulation (DBS), miniaturized from human Parkinson’s treatment protocols, to restore function in mice with dystonia.
  • “We had a mouse with a very severe dystonia… We started stimulating regions of the cerebellum to resolve it and reverse the movement problems that we induce.” (31:43)
• Ultimate challenge: DBS works while active, but symptoms return when stimulation stops. The lab’s next step is “closed loop” DBS, using the brain’s signals to start/stop stimulation as needed—moving toward the brain teaching itself. (33:23)

5. On Hadley’s Rare Mutation (POU4F1)

• Only about 30 cases of Hadley’s mutation are identified worldwide. (35:34)
• “Once somebody’s identified and the population grows, there are many kids and potentially adults around the world who have similar mutations. We just didn’t know this is what they had.” (35:34)
• POU4F1 gene: its mutation primarily affects the cerebellum, causing motor and speech issues, but not necessarily intellectual impairment.
• “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.” (37:25)
• Dr. Sillitoe’s vision: combining deep brain stimulation with gene therapy, teamwork across specialties, and tailored interventions.

6. The Realities of Rare Disease Research

• Funding is vital but hard to secure, especially for “orphan” diseases. “Without the funding, I don’t have a job. There is no science, there’s absolutely nothing.” (41:51)
• Public can help via dedicated donation links (Giv Now CSC)—plugged by Daniel Tosh, who humorously contrasts it with show merch. (43:31)
• For impactful progress, Dr. Sillitoe’s lab needs $500,000–$1 million per year; to accelerate toward cures, “three, four, five times that.” (46:40)

7. Looking to the Future: Technology, AI, and Hopes for a Cure

• AI offers promise but is limited by gaps in our anatomical knowledge; “There’s a lot of promise, but who knows?” (41:46)
• Dream scenario: non-invasive therapies that reprogram neural circuits and correct the molecular/genetic cause—“You walk into a clinic, you have some kind of stimulation… that actually fixes your brain communication, activates certain genes, dampens the bad genes, and you walk out.” (53:53)
• 20-year timescale for non-invasive, effective interventions is plausible—“maybe” for the whole dream package. (53:56)

8. Down-to-Earth, Human Moments

• Discussion of Hadley’s day-to-day, her questions for Daniel, and Tosh’s livestock and farm antics brings warmth and levity.
• Running joke about gifts—Tosh bestows random household items on guests (“Here’s a putter. I’ve never golfed. I will now.” – Dr. Sillitoe, 51:05)
• Dr. Sillitoe’s personal side: early gym routine, healthy lifestyle adaptation post-cholesterol wakeup call, joys of family (48:49, 49:26)
• Daniel’s off-beat curiosity: “Do you fuck with medulla oblongata?” (39:30)
• Humorous riff: could we create “Rat Jesus” from the Shroud of Turin’s DNA? Dr. Sillitoe: “That is actually a trivial experiment to do...” (54:37)

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Notable Quotes & Memorable Moments

• Hadley explains “magic medicine”:

  • “Magic medicine is what old Dr. Roy’s working on.” – Daniel Tosh (55:36)

• On the cost of research:

  • “I probably spend about $75,000 a year on mice, which is a lot.” – Dr. Roy Sillitoe (30:17)

• On gene mutation effects:

  • “A different mutation in the same gene can cause epilepsy... a third mutation... can cause migraines. So seemingly very different problems. One gene.” – Dr. Roy Sillitoe (25:18)

• On the promise of new therapies:

  • “We can train the cerebellum to almost fix itself…and these mice with dystonia show almost no signs... after three months without stimulation.” – Dr. Roy Sillitoe (53:41)

• Tosh, ever the comic:

  • “Do you look around Texas and wonder if every other person you talk to has a genetic mutation?” (01:00, also revisited at 33:42)
  • “I would have just turned the knob a little more. Turn it up, give them a little more juice.” (33:28)

• On the emotional toll for families:

  • "When you have a child that needs extreme care...you’re basically handcuffed for the rest of your life...I have to be by this specific hospital or I have no shot.” – Daniel Tosh (38:41)

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Important Timestamps

| Timestamp | Segment | |-----------|------------------------------------------------------| | 08:17 | Introduction to Hadley, the rarity of her disorder | | 19:41 | Dr. Sillitoe’s introduction and background | | 24:30 | Simple explanation of Dr. Sillitoe’s job | | 25:18 | How one gene mutation can cause many problems | | 27:20 | What is the cerebellum? | | 27:56 | Explaining dystonia | | 30:17 | Mice in research, the cost and process | | 31:43 | Stimulating the cerebellum in dystonia mice | | 33:23 | Closed-loop brain stimulation | | 35:34 | The rarity of Hadley's mutation | | 37:25 | Hadley’s intellectual abilities vs. motor limitations| | 41:51 | The reality and difficulty of funding | | 43:31 | How listeners can help fund research | | 46:40 | Funding needs for the lab (“half a million to a million per year”)| | 53:41 | Dream scenario for the future of brain stimulation |

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Tone and Highlights

True to form, Daniel Tosh keeps the conversation lively with irreverent, sharp humor, but maintains genuine warmth and curiosity. Hadley brings openness and charm, while Dr. Sillitoe grounds the show in scientific clarity, optimism, and humility. The episode’s emotional core is the reality of living with and fighting rare diseases—a reality softened and made hopeful by laughs, love, and the promise of science.

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Summary

This is an episode for anyone interested in human stories behind medical science, the painstaking fight for rare disease treatments, and the intersection of family, hope, and unfiltered comedy. Listeners come away with a deeper understanding of how gene mutations can affect lives, the intricacies and hurdles of neurological research, and an appreciation for the tireless work required to turn science into cures—sprinkled with enough Tosh-isms to keep things light.

Transcript

[Daniel Tosh]

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[Howie Mandel]

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[Daniel Tosh]

Do you look around Texas and wonder if every other person you talk to has a genetic mutation?

[Dr. Roy Sillitoe]

I do, actually. I'm always curious about. I think we all have mutations. We all have tons of mutations.

[Daniel Tosh]

Tosh show. Tosh show for show. ENG10. It's Dan Tosh with Eddie Gosling.

[Eddie Gosling]

What's up, Dan Tosh? What you got for us today, big guy? Sit back.

[Daniel Tosh]

You know what I'm doing right now.

[Eddie Gosling]

What are you doing?

[Dr. Roy Sillitoe]

Pause.

[Eddie Gosling]

What you doing?

[Daniel Tosh]

I'm waiting for AI to take over. Hey, man, Go ahead, AI.

[Eddie Gosling]

What you're doing, you're okay playing with fire?

[Daniel Tosh]

Go ahead, AI. See what you can do.

[Eddie Gosling]

Yeah. I don't see anything. Nothing.

[Daniel Tosh]

AI thinks it's got me. No, it doesn't got me.

[Eddie Gosling]

You got it.

[Daniel Tosh]

You think you don't need me. You need me, Ed. You don't need me.

[Eddie Gosling]

I need you, buddy.

[Daniel Tosh]

Oh, that's the nicest thing. Hey, I got a new chicken.

[Eddie Gosling]

Okay.

[Daniel Tosh]

Okay. This breeder, I don't know if they're called a breeder or whatever. These people that we get chickens from somebody, they just reached out and said, hey, I got a. I got this Polish hen. They're not sexed yet, meaning they don't know if it's a. Okay, 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, what's her name? Who's the big golden girl? Yeah, like a Bea Arthur of the group.

[Eddie Gosling]

I see that.

[Daniel Tosh]

Yeah, like a little Bea 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? 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.

[Eddie Gosling]

Okay?

[Daniel Tosh]

Now it's covered. That's got poop on it. That's poop.

[Eddie Gosling]

Nice.

[Daniel Tosh]

That's poop. Okay. That is dried. You scratch that poop off if you want. There you go. But this. 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 are. They're all covered in crap. You're getting the gist.

[Eddie Gosling]

I am.

[Daniel Tosh]

Okay. I'm gonna keep those on my desk. All of a sudden, I get this egg

[Eddie Gosling]

what that looks like a piece of, like a candy egg?

[Daniel Tosh]

Raw? No. So I look it up when a new hen. Like, sometimes it can happen when they get frightened.

[Eddie Gosling]

Okay.

[Daniel Tosh]

Or just like when they just are starting to lay. It's called a fart egg.

[Eddie Gosling]

A fart egg.

[Daniel Tosh]

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?

[Eddie Gosling]

Pete.

[Daniel Tosh]

Pete.

[Eddie Gosling]

Pete does.

[Daniel Tosh]

Pete loves eggs. So guess what? I brought Pete in a whole slew of eggs today.

[Eddie Gosling]

This is from Tosh Farms.

[Daniel Tosh]

This is from my farm. Look at how much poop is on this egg.

[Eddie Gosling]

There's so much turds on these.

[Daniel Tosh]

Look at that one. That one is just covered in shit.

[Eddie Gosling]

That was a tough get out.

[Daniel Tosh]

Okay. That was a stubborn egg. But look at this one. Look right here. This one's beautiful. That's a big egg.

[Eddie Gosling]

Yeah.

[Daniel Tosh]

Next to a little fart egg.

[Eddie Gosling]

Little fart egg.

[Daniel Tosh]

So I'm dying to know Pete, you wanna put this in a little tiny cup and pretend you're Rocky?

[Hadley]

Yeah.

[Daniel Tosh]

You just drink this little fart egg. What? Can I put this fart egg in here? We 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 eggs. You know you crack eggs on the rim.

[Eddie Gosling]

I do.

[Daniel Tosh]

I don't.

[Dr. Roy Sillitoe]

Yeah, you can't do that.

[Daniel Tosh]

That's bad, Ed. I'll tell you why.

[Dr. Roy Sillitoe]

Flat surface.

[Daniel Tosh]

Because then it's. You end up getting egg yolk on the backside 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's. Guess what?

[Eddie Gosling]

Hardest rock.

[Daniel Tosh]

I didn't make any progress.

[Dr. Roy Sillitoe]

Oh, there she is.

[Daniel Tosh]

Dry as a cucumber. Look at that. Now there's, like, a black. Oh, no, that's not. That's not the shell. What is this? So inside. Maybe it dried up, because this happened quite a few days ago.

[Dr. Roy Sillitoe]

Treasure map.

[Daniel Tosh]

No, but, like, it's like. You see how it's a baby. Can you see it almost looks like glass. Huh. Well, that's my first fart egg. But, Pete, come get your. Your loot.

[Eddie Gosling]

You just chew on this one, buddy.

[Dr. Roy Sillitoe]

I think Pete should down all those eggs right now.

[Daniel Tosh]

You excited about all these eggs? How many eggs did I give you there? That's more than a dozen. Oh, you know what else? I got a new Mandarin tree. Well, 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?

[Dr. Roy Sillitoe]

Yes.

[Daniel Tosh]

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 Mandarins. 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. Those apples that were horrible. I thought maybe I could give him a bunch of mandarins for his children to play with. At least if they dig their fingernails in there, their fingernails will smell nice.

[Dr. Roy Sillitoe]

Okay, thank you.

[Daniel Tosh]

Here you go, John. This is for you. Bull sucks. So that's what's going on over there at Tosh Farms.

[Eddie Gosling]

It's a lot.

[Daniel Tosh]

It is a lot. You know how long it took me to do one tree of produce like that?

[Eddie Gosling]

How much?

[Daniel Tosh]

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's crown. They're just straight knives. They bite back, stick out.

[Eddie Gosling]

Yeah.

[Daniel Tosh]

Is that what they put on top of Jesus head on the crucifix?

[Dr. Roy Sillitoe]

Yeah. Lemon thorns.

[Daniel Tosh]

Just a branch of lemons. Good gosh. Lemon trees are pokey.

[Dr. Roy Sillitoe]

Someone's like, that's the forbidden fruit.

[Eddie Gosling]

Hey, has your hen laid any eggs since the fart egg?

[Dr. Roy Sillitoe]

Yeah.

[Eddie Gosling]

Yeah, fine. They all seem normal.

[Daniel Tosh]

Great.

[Eddie Gosling]

Okay.

[Daniel Tosh]

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 a ultra rare neurological disorder. And Lord knows she's had to go through a hundred times what any human should ever have to go through in life. But 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 paw show. My guest today is by far my favorite niece on my wife's side of the family. She's 1 in 276,666,666.66. Repeating, of course, literally. Please welcome Hadley. Thank you for being here. How are you doing today?

[Hadley]

Go.

[Daniel Tosh]

Okay, Ready for your first question?

[Hadley]

Yeah.

[Daniel Tosh]

Okay. Do you believe in ghost?

[Hadley]

Oh, no.

[Daniel Tosh]

You don't believe in ghosts?

[Hadley]

No.

[Daniel Tosh]

Good for you. So smart. Okay, next question I ask. All my guests are boys. Gross. No, no. Is there someone interesting in your life?

[Hadley]

Yeah.

[Daniel Tosh]

Yeah. Hadley, how old are you?

[Hadley]

9.

[Daniel Tosh]

19.

[Dr. Roy Sillitoe]

No.

[Hadley]

9.

[Daniel Tosh]

What?

[Dr. Roy Sillitoe]

9.

[Daniel Tosh]

9. When is your birthday?

[Hadley]

November.

[Daniel Tosh]

November 4th. And what do you want for your birthday?

[Hadley]

A puppy toy.

[Daniel Tosh]

You just love puppies. Do you like your dog?

[Hadley]

Yeah. Puppy is a good puppy.

[Daniel Tosh]

Doggie Betty. How old is Betty now? Do you like my pig, Potato?

[Hadley]

Yes.

[Daniel Tosh]

Are you scared of Potato? No. Would you take Potato home if I said you could have them?

[Dr. Roy Sillitoe]

Yeah.

[Daniel Tosh]

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 no one ever heard of. Next thing you know, you have this exotic cat. What is your cat's name?

[Hadley]

Sugar Cookie.

[Daniel Tosh]

Sugar Cookie. Do you go to school?

[Hadley]

Yeah.

[Daniel Tosh]

Is school hard?

[Hadley]

No.

[Daniel Tosh]

Any cute boys in your class? Yeah, there are.

[Hadley]

Yeah.

[Daniel Tosh]

Interesting.

[Hadley]

Yeah.

[Daniel Tosh]

Who do you like in your class?

[Hadley]

Um. Bode.

[Daniel Tosh]

Oh, Bode. Do you have a boyfriend?

[Hadley]

Yeah.

[Daniel Tosh]

You do? Yeah. Oh, man. Is it serious? No, not yet. All right. You are a big fan of Ed Sheeran.

[Hadley]

Yeah.

[Daniel Tosh]

What's your favorite Ed Sheeran song?

[Hadley]

All of them.

[Daniel Tosh]

All of them?

[Hadley]

Yeah. Oh.

[Daniel Tosh]

I mean, he's got a couple stinkers. They all sound the same. Is that what you meant to say?

[Hadley]

No.

[Daniel Tosh]

Okay. Hey, you got really good at swimming.

[Hadley]

Yeah.

[Daniel Tosh]

Although yesterday you had a bit of a belly flop.

[Hadley]

I don't go. But I'm not good in your pool.

[Daniel Tosh]

You're pretty good in my pool. Now, do we want to go surfing again? The surf is pretty big right now.

[Dr. Roy Sillitoe]

Go fast. Go.

[Daniel Tosh]

Can you be honest with me? Who is your favorite uncle? Go ahead.

[Hadley]

Uncle Daniel.

[Daniel Tosh]

That's right. That's right. Did you hear that, Chase? Uncle Daniel. Okay, Hadley, do you have any questions for me? Go ahead.

[Hadley]

What is your favorite kind of dog?

[Daniel Tosh]

What's my favorite kind of dog?

[Hadley]

Yeah.

[Daniel Tosh]

It's for me to own versus my favorite kind. I think my favorite dog might be a whippet. And they're like skinny little greyhounds or smaller. They're the fastest. They're so fast. I think that's beautiful. But I also love an Australian Shepherd. They're beautiful with the different colored eyes. I like that you have pretty eyes. But I mean, I kind of just like Carl.

[Hadley]

All right.

[Daniel Tosh]

You know, he's just. He's just a little. He's kind of a cuddly little muppet.

[Hadley]

Yeah.

[Daniel Tosh]

Although he does eat my daughter's poop. And that's disgusting.

[Mira Potassan]

Ew.

[Daniel Tosh]

I know. Everybody that's on my show gets a gift. Okay. Okay. So I have to give you some gifts. You ready?

[Hadley]

Yeah. Yeah. Hope this will pop.

[Daniel Tosh]

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 gonna give it to Hadley. So here, you get that. Okay. Put that on the floor. You're not gonna. Then you can just drop it. Hadley. Hallie. Then you like to look at this photo all the time, don't you?

[Hadley]

Yeah.

[Daniel Tosh]

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 to your mom. Oh, yeah, she's going to love them. She's going to love these. Oh, you're going to love them. And you can use them to make your hair smell. How often do you wash your hair?

[Hadley]

Lifetime?

[Dr. Roy Sillitoe]

Five.

[Daniel Tosh]

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 got? Orbeez? Oh, yeah. It's expensive stuff. Oh. Do you ever wear a face mask?

[Hadley]

No.

[Daniel Tosh]

Oh, well, your skin looks lovely. You could try these. They have face masks, too. This is great. What do you think of all this? We're just gonna push this all over there. You know the drill. Throw it to the floor. Hadley, just do it. Hadley, just do it. Throw it. Throw it. All of it. There we go. Oh, it's perfect. Hadley, thank you for respecting the desk. Hey, I have one more gift for you. Now, you know Panda?

[Hadley]

Yeah.

[Daniel Tosh]

You know her brother John? John?

[Hadley]

No.

[Daniel Tosh]

He was in Mexico. He got a hand job from a masseuse. I don't even want to go into that.

[Dr. Roy Sillitoe]

Yeah, Yeah, I did.

[Hadley]

Okay.

[Daniel Tosh]

Okay. Okay. He always buys me gifts. I always end up giving them away. Anyway, he bought me a pair of shoes and guess what? I loved them. I loved them. I thought 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. You think your dad will like those shoes?

[Dr. Roy Sillitoe]

Yeah.

[Daniel Tosh]

Again, I don't understand. I mean, those aren't twelves. Oh, man. What size your dad. We're at seven, seven and a half. It's not. It doesn't matter. Anyway, you give these to your father, you tell him, good luck beating me in pickleball. 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 on the floor.

[Hadley]

You're welcome.

[Daniel Tosh]

You're welcome. We'll be right back. This episode is brought to you by Pocket Hose, the world's number one expandable hose. Old fashioned hoses get kinks increases at the spigot, but the Copperheads pocket pivot swivels 360 degrees for full water flow and freedom to water with ease all around your home. Plus super light ultra durable pocket hose Copper Head is backed with a 10 year warranty. The brand new Pocket Hose Copperhead with Pocket Pivot is a total game changer. I hate coiling up an old rubber hose as much as the next guy. Actually, probably less. I don't mind it. I got nothing to do. But Eddie on the other hand, oh, he hates coiling up a hose. You watering in the yard of your house?

[Dr. Roy Sillitoe]

Nope.

[Daniel Tosh]

Come on Ed. I love watering a yard. For a limited time, my listeners can can get a free Pocket Pivot and their 10 pattern sprayer with the purchase of any size Copperhead hose. Just text DAN to 64,000. That's DAN to 64,000 for your two free gifts with purchase DAN 64,000. Message and data rates may apply. See terms for details. Let's be honest. Clothes shopping, not my thing. I just want to walk out the door feeling great in what I'm wearing. Maybe get a compliment or two. Ever order three sizes of the same shirt? Just hoping one fits? Scroll shop, add to your cart and still end up returning everything. Same here. That's why you need to switch to Stitch Fix. You just take a quick style quiz, share your size, your vibe and your budget and boom. You're matched with a real human stylist. Who who handles the rest. You get to be fancy like me and have your own personal stylist. They send you a fixed box with clothes that actually fit and make sense for your life, your job, whatever. It saves you time. You look great and feel confident in what you're wearing. It's no risk. All style. Try it all in the comfort of your home. Keep what works, send back the rest. Shipping returns are always free and no subscription required. Plus get a free try on for your first order. Just be prepared for compliments. Get started today@stitch fix.com tosh. You get $20 off your first order. That's stitchfix.com tosh. 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 available equipment. The workouts adapt to your growth, so each workout is challenging enough to push you to make progress, but not too challenging that you end up putting a hole in your wall. Fitbod even tracks your muscle recovery so you can avoid burnout and keep up your momentum. How do they do it? It's fine tuned by experienced, certified personal trainers to bring best practices and exercise science to you. How's it going over there, Pete? You still using it?

[Dr. Roy Sillitoe]

We're still using Fitbod. We're in month two with the app.

[Daniel Tosh]

You're in month two? 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. Me tosh. That's F I T B O D Metosh. 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 Sillitoe.

[Dr. Roy Sillitoe]

Thank you very much, Daniel. Pleasure to be here.

[Daniel Tosh]

That's a mouthful.

[Dr. Roy Sillitoe]

It is. It's been a mouthful getting to all these places.

[Daniel Tosh]

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?

[Dr. Roy Sillitoe]

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.

[Daniel Tosh]

I mean, beautiful.

[Dr. Roy Sillitoe]

I know, that's a tough one.

[Daniel Tosh]

Are you kidding me? Did you ever go up to Whistler?

[Dr. Roy Sillitoe]

Oh, we did. Yeah, absolutely.

[Daniel Tosh]

It's just delightful.

[Dr. Roy Sillitoe]

Yes, it's amazing. I went skiing once. I'm kind of an embarrassment for anybody that grew up in Canada that actually don't know how to ski.

[Daniel Tosh]

Can you ice skate?

[Dr. Roy Sillitoe]

I'm not bad. I'm okay.

[Daniel Tosh]

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.

[Dr. Roy Sillitoe]

We had to. So part of growing up in Canada is that, you know pe, you get to play hockey. And so that was my introduction to ice hockey was in PE so sort of could skate and I, I did my best, but it was not pretty. But I tried.

[Daniel Tosh]

You're. 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.

[Dr. Roy Sillitoe]

Right.

[Daniel Tosh]

That could have been your role.

[Dr. Roy Sillitoe]

It could have been, but in high school, I. I was kind of a mommy' so might need my mom to back me up.

[Daniel Tosh]

All right, here I go. First question. Do you believe in ghosts?

[Dr. Roy Sillitoe]

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.

[Daniel Tosh]

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?

[Dr. Roy Sillitoe]

I was 12 years old when I moved to Canada from Africa.

[Daniel Tosh]

How was that transition?

[Dr. Roy Sillitoe]

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.

[Daniel Tosh]

And you were 12?

[Dr. Roy Sillitoe]

I was 12. My dad and mom's, you know, vision was to get us out of Africa, to get us an 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, get a better education. So I followed up my brothers, who were in Vancouver.

[Daniel Tosh]

So you lived with your brothers as they became the head of the household?

[Dr. Roy Sillitoe]

Yes.

[Daniel Tosh]

How did that work out?

[Dr. Roy Sillitoe]

I gotta 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.

[Daniel Tosh]

Actually, 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.

[Dr. Roy Sillitoe]

So my brother was actually. Could be my legal guardian, huh? Yep.

[Daniel Tosh]

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 are here. Your grandfather helped start the MI5 in England. Did your grandfather know Jackson Lamb?

[Dr. Roy Sillitoe]

So first it's my great grandfather, great

[Daniel Tosh]

grandfather started the MI5.

[Dr. Roy Sillitoe]

He did.

[Daniel Tosh]

He was part of the group that started it.

[Dr. Roy Sillitoe]

Well, he was the head of the MI5.

[Daniel Tosh]

He was first desk.

[Dr. Roy Sillitoe]

Well, so the story goes that he was, he was a law enforcement officer and pretty strict guy. And he was grumpy, writing out Ministry of information room number five. And so he decided we're calling it the MI5. The office was there, of course, but

[Daniel Tosh]

he coined the MI5 was your great grandfather James Bond?

[Dr. Roy Sillitoe]

Well, he was the real life James Bond. It was written after him. So of course, you know, 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 would, he was trying to get, take every opportunity to go back. So when De Beers diamond company came calling to help solve the diamond smuggling cause 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 the story and it, you know, he kind of adapted it. It sounded, you know, sexy in his mind and it was, it was amazing story. So he is the real life James Bond.

[Daniel Tosh]

What kind of car did he drive?

[Dr. Roy Sillitoe]

I actually don't know. Probably a very cheap car given by law enforcement.

[Daniel Tosh]

You're the smartest person we've interviewed and we've spoken to tons of people from Stanford. Huh. Explain to me, as if I'm a fourth grader, what your job involves.

[Dr. Roy Sillitoe]

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.

[Daniel Tosh]

How many problems can one gene mutation cause?

[Dr. Roy Sillitoe]

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.

[Daniel Tosh]

Can there be good mutations? I mean, I don't know what good is, but, like, can some gene mutation be, like, that causes something extraordinary in the positive?

[Dr. Roy Sillitoe]

I don't think so. I don't have any evidence, at least from the cerebellum, where, you know, there's one problem that causes a dysfunction and a second one resolves it in some way. I'm not aware of, of that.

[Daniel Tosh]

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?

[Dr. Roy Sillitoe]

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 basically black out.

[Daniel Tosh]

I'd black out. I'd vomit.

[Dr. Roy Sillitoe]

Yes, me too. Absolutely terrible. When I left Africa, they stopped. Age is one thing in terms of, you know, migraines. There's so much going on. It's not only a neuroproblem, but there's issues with the blood, the vasculature. There's issues with pressure is another one, depending on where you live. So it could be where you actually moved during your life, could have actually impacted that wasn't that.

[Daniel Tosh]

Okay, it was something, but it just stopped. What is a cerebellum and who has one?

[Dr. Roy Sillitoe]

The cerebellum is just the coolest part of the brain.

[Daniel Tosh]

Oh.

[Dr. Roy Sillitoe]

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.

[Daniel Tosh]

You dream about that?

[Dr. Roy Sillitoe]

I dream about the cerebellum. I dream about experiments. I'm sorry. I dream about experiments.

[Daniel Tosh]

Such a nerd.

[Dr. Roy Sillitoe]

And, you know, half the experiments that I've worked in my lab actually came from dreams.

[Daniel Tosh]

Oh, I don't know if I like that.

[Dr. Roy Sillitoe]

No, I know. But they keep going and going.

[Daniel Tosh]

Okay, Okay.

[Dr. Roy Sillitoe]

I guess I've let the cat out of the bag for all my students when they say, Roy came up Crazy idea. I didn't come up with a crazy idea. I dreamt about it.

[Daniel Tosh]

Okay, Dystonia. What is it?

[Dr. Roy Sillitoe]

Dystonia 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 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. 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.

[Daniel Tosh]

Ed, you remember that cheerleader for Washington, right?

[Eddie Gosling]

She could walk back.

[Daniel Tosh]

Yeah.

[Hadley]

Let me.

[Daniel Tosh]

I think it was proven that she was a faking dystonia, wasn't it? Or no.

[Eddie Gosling]

Could be. I don't.

[Daniel Tosh]

There was this one where she. Do you know who I'm talking about?

[Dr. Roy Sillitoe]

I know who you're talking about.

[Daniel Tosh]

Her movements were herky jerky and all over the place, but she could walk backwards fine. So. Not that this is important, but she was a smoke show, so. 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.

[Dr. Roy Sillitoe]

It is real.

[Daniel Tosh]

No, I didn't know that her case was right. I thought she was called out, so

[Dr. Roy Sillitoe]

she was called out, and I did watch the video.

[Daniel Tosh]

And you said yes or no?

[Dr. Roy Sillitoe]

Well, it looks real. It looks real. But. But I. You know, I've. I've never spoken to her to actually see whether it was real.

[Eddie Gosling]

Did you learn about the video from our show Tosh0 oh, man.

[Dr. Roy Sillitoe]

I don't know where I heard about it.

[Daniel Tosh]

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 seem to be the go to animal when testing eventual cures for humans. Is that why we like cheese so much?

[Dr. Roy Sillitoe]

It very well could be. We all have a little bit of mouse in us, I'm sure.

[Daniel Tosh]

What's your mice budget?

[Dr. Roy Sillitoe]

It's actually shockingly high.

[Daniel Tosh]

No, I believe you.

[Dr. Roy Sillitoe]

It's. I probably spend about $75,000 a year on mice, which is a lot.

[Daniel Tosh]

No, I mean, I know. All right, so. But you did. You gave mice dystonia.

[Dr. Roy Sillitoe]

Well, so what we did, we had been studying several different genes that we knew caused dystonia in 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, it's 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 from. But block the brain from communicating properly. And this was. We directed the mutation to the cerebellum, and we created a very severe dystonia in mice. And 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. The movement problems that we induce.

[Daniel Tosh]

And by stimulating. Is it just electrocuting? What are you doing?

[Dr. Roy Sillitoe]

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.

[Daniel Tosh]

And how long will that last?

[Dr. Roy Sillitoe]

So you can so 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. My. The hurdle we've been facing in the lab is that we've been able to apply the deep brain stimulation in mice for ataxia, for dystonia, 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 it goes back to being abnormal, the deep brain stimulation kicks in again. So we're essentially using the brain to teach itself.

[Daniel Tosh]

It's like a generator for when the electricity goes out.

[Dr. Roy Sillitoe]

Yeah, so it absolutely is. Yes.

[Daniel Tosh]

That's better than what I would have come up with. I would have just turned the knob a little more.

[Dr. Roy Sillitoe]

Turn it up, give them a little

[Daniel Tosh]

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?

[Dr. Roy Sillitoe]

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. Oh, 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, a genetic disorder.

[Daniel Tosh]

How did you come to know my niece?

[Dr. Roy Sillitoe]

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 ret, and by chance, this gene was expressed in the cerebellar system, and he wasn't super interested in cerebellum. Oh, you should use this. I think it could tell you something. And I looked at his data.

[Daniel Tosh]

That's what I think they'd be talking about. Okay.

[Dr. Roy Sillitoe]

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 scientists, 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.

[Daniel Tosh]

How rare is her mutation?

[Dr. Roy Sillitoe]

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's 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.

[Daniel Tosh]

Explain what pou4f1 is and if it is also your license plate.

[Eddie Gosling]

Is it.

[Dr. Roy Sillitoe]

No, it's. It's not my license.

[Daniel Tosh]

Sounds like a confirmation code. Does this have a fun name, or is it just Pou4F1?

[Dr. Roy Sillitoe]

It's got a fun name. So the genes are named for where they're expressed, and in this case, it's what the. The. The region that it's in actually does as a protein.

[Daniel Tosh]

Got it.

[Dr. Roy Sillitoe]

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.

[Daniel Tosh]

That's just the specific one.

[Dr. Roy Sillitoe]

Yes.

[Daniel Tosh]

That she has to deal.

[Dr. Roy Sillitoe]

Yes.

[Daniel Tosh]

All right. I mean, I don't know if it's a high priority, but could we rename it Anybody? Yes. Tosh. Tosh.

[Dr. Roy Sillitoe]

Titus, this nomenclature committee is out there, all right? And they love naming genes.

[Daniel Tosh]

What is causing Hadley's symptoms?

[Dr. Roy Sillitoe]

From what I understand, a lot of them would be caused by cerebellar problems, particularly here. Motor issues, speech issues, for sure. Are driven heavily by cerebellum.

[Daniel Tosh]

Is she trapped in her like, is she comprehending way more than she's able to express?

[Dr. Roy Sillitoe]

That's a great question. 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.

[Daniel Tosh]

I mean, is that torture?

[Dr. Roy Sillitoe]

It's frustrating for kids and adults with that. It's absolutely frustrating.

[Daniel Tosh]

Well, how are you trying to treat her mutation?

[Dr. Roy Sillitoe]

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.

[Daniel Tosh]

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'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.

[Dr. Roy Sillitoe]

Yeah.

[Daniel Tosh]

Does Stephanie, my sister in law, have your cell phone number?

[Dr. Roy Sillitoe]

Yes.

[Daniel Tosh]

Oh, man. Does she send you long texts?

[Dr. Roy Sillitoe]

Yes.

[Daniel Tosh]

Where like, you need a medical degree to fucking understand them.

[Dr. Roy Sillitoe]

You know, I appreciate them because I'm

[Daniel Tosh]

sure you can understand them. Like, I'm just trying to get highlights and maybe some cool pics.

[Dr. Roy Sillitoe]

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.

[Daniel Tosh]

Yeah, no, that's not me. I'm writing like a child still. I refuse to capitalize. Do you fuck with medulla oblongata?

[Dr. Roy Sillitoe]

I do a lot, actually. It's. Well, pou4f1 does have expression in the medulla oblongata and it's that connection to the cerebellum that is problematic.

[Daniel Tosh]

You mentioned millions of people have cerebellum issues and that it's linked to everything from autism to sleep disorders to alcoholism.

[Dr. Roy Sillitoe]

Yep.

[Daniel Tosh]

Dylan back there, his cerebellum I don't know if you need to look at the guy drinks just constantly. Almost doesn't affect him. Is that something we should worry about?

[Dr. Roy Sillitoe]

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.

[Daniel Tosh]

Do you drink alcohol at all?

[Dr. Roy Sillitoe]

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.

[Daniel Tosh]

Is there a part of the brain you could touch with electrodes that would make Eddie and I better at spelling?

[Dr. Roy Sillitoe]

Probably. I, I would guess there is.

[Daniel Tosh]

Oh, wow.

[Dr. Roy Sillitoe]

You know, I, I think it would still take a bit of practice.

[Daniel Tosh]

You ever see that John Travolta movie where he got struck by lightning Phenomenon?

[Dr. Roy Sillitoe]

That's my favorite movie. Absolutely love that movie.

[Daniel Tosh]

He's just smart for like a month

[Dr. Roy Sillitoe]

or something like that and then he dies.

[Daniel Tosh]

Listen, that's a lot of electricity hitting his brain. You're not going to live for a long time with that much juice.

[Dr. Roy Sillitoe]

Absolutely love that movie.

[Daniel Tosh]

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.

[Dr. Roy Sillitoe]

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, you know, 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?

[Daniel Tosh]

I'm not doing it. It's not for me. How crucial is funding to your work?

[Dr. Roy Sillitoe]

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, postdoctoral fellows, 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, there is no Science, there's absolutely nothing.

[Daniel Tosh]

But the schools can't cut the big checks.

[Dr. Roy Sillitoe]

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.

[Daniel Tosh]

When you specialize in such rare conditions, is it harder to get funding?

[Dr. Roy Sillitoe]

Yeah, it is, much harder.

[Daniel Tosh]

I mean, because if you would focus on hair loss. Right. The money just pours in.

[Dr. Roy Sillitoe]

I'd be my first client. Well, but no, I'll give you a few. 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, it's understandable in one way that a lot of the resources go to what is affecting millions and millions of people.

[Daniel Tosh]

How can people help with funding for your research? Do you have an OnlyFans page?

[Dr. Roy Sillitoe]

I do not. But we do have a site that we've created where people can support us.

[Daniel Tosh]

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 Giv now. Csc. We'll be right back. A thoughtfully built wardrobe comes down to pieces that mix well and last. That's where Quince shines. Premium fabrics, everyday essentials that feel effortless to wear and dependable even as the seasons change. Quince works directly with top factories and cuts out the middleman. You're not paying for brand markup or fancy retail stores, just quality clothing. Their cashmere's 100% Mongolian. The same stuff luxury brands use. The Pima cotton is long staple, which means it stays soft and doesn't pill. The European jersey linen is breathable and lightweight and everything is built to hold up to regular wear and still look good. How's your Quince clothing coming along, fellas?

[Eddie Gosling]

Wearing my T shirt today.

[Dr. Roy Sillitoe]

I'm wearing a Quints T shirt too, man.

[Daniel Tosh]

Three out of the four of us are wearing Quint's shirts right now. Go to quince.comtosh for free shipping and a 365 day return. That's a full year to build your wardrobe and love it and you will now available in Canada too. Don't keep settling for clothes that don't last. Go to Queen nce.comtosh for free shipping and 365 day returns. Quince.comtosh this episode of Tosh show is brought to you by Progressive Insurance. Fiscally responsible financial geniuses, monetary magicians. These are things people say about drivers who switch their car insurance to progressive and Save hundreds. Visit progressive.com to see see if you could save Progressive Casualty Insurance company and affiliates. Potential savings will vary. Not available in all states or situations.

[Mira Potassan]

Hi, my name is Mira Potassan. I'm an author and I'm an activist and GoFundMe is my go to platform for fundraising. The first GoFundMe I did was to raise money for a chat book or a collection of poetry and essays and short stories. So we started a GoFundMe and our goal was 7,000. What I've learned is so special about GoFundMe is that it's a whole collection of people offering anything from like $4 to $400. And each time you get a ping that someone donated, even if it is just $4, it's so exciting. So if you have a goal and you get there, you can keep making it bigger and bigger and bigger. We did go past our goal. It was amazing.

[Dr. Roy Sillitoe]

GoFundMe is the world's number one fundraising

[Daniel Tosh]

platform, trusted by over 200 million people. Start your GoFundMe today at gofundme.com that's gofundme.com gofundme.com. PAW show what do you need a year to make things like, oh, now

[Dr. Roy Sillitoe]

we're cooking for me right now my lab probably needs about half a million to a million per year.

[Daniel Tosh]

Seems totally obtainable, Ed.

[Dr. Roy Sillitoe]

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 if things were rolling, let's say we need to solve the big problems. I say we need three, four, five times that.

[Daniel Tosh]

Okay.

[Dr. Roy Sillitoe]

Because at the pace we're going to, 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.

[Daniel Tosh]

Well, how soon are you to actually trying to stimulate like a human brain? Have you done it?

[Dr. Roy Sillitoe]

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.

[Daniel Tosh]

You also could. I mean, besides the things you mentioned, you also said you could. Like posture is one.

[Dr. Roy Sillitoe]

Yeah.

[Daniel Tosh]

Cause 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 gonna like it. It's gonna. And I'll sign any waiver that says I don't care what you do. Just go ahead and start poking.

[Dr. Roy Sillitoe]

There's many spots I can think of that might help the posture. I'm not sure about the hunchback, but.

[Daniel Tosh]

Well, it's just gonna 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 pastimes?

[Dr. Roy Sillitoe]

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, cerebellum kids. My son's gonna 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.

[Daniel Tosh]

You work out like a crazy person.

[Dr. Roy Sillitoe]

It's early. It's crazy early. But what time.

[Daniel Tosh]

What time do you get up?

[Dr. Roy Sillitoe]

I get up at 4am how often?

[Daniel Tosh]

What time do you go to bed?

[Dr. Roy Sillitoe]

10:30.

[Daniel Tosh]

Guess what? I'm gonna give you some advice, okay? You need a little more sleep.

[Dr. Roy Sillitoe]

I know.

[Daniel Tosh]

A little more sleep.

[Dr. Roy Sillitoe]

Yes.

[Daniel Tosh]

That's not. That's not ideal. 10:30 to 4:30. Nah, you need a little bit more. It's not horrible.

[Dr. Roy Sillitoe]

Unwinding is hanging out with my wife and kids.

[Daniel Tosh]

Do your kids work out?

[Dr. Roy Sillitoe]

My son started about a year ago. He's always been in sports, but he's never actually worked out until this last year.

[Daniel Tosh]

Do you do everything with health? Because physical is a big part of this as well.

[Dr. Roy Sillitoe]

Yeah. So what do you mean by everything?

[Daniel Tosh]

I don't know. Like you watch everything that goes into your body, food wise. Do you take, you know, supplements?

[Dr. Roy Sillitoe]

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 and he says Your cholesterol is bad. He says, either do something or you're gonna 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. Cause the food is so good and it's so bad for you. 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 and exercise in an age appropriate way.

[Daniel Tosh]

You do cardio?

[Dr. Roy Sillitoe]

I 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.

[Daniel Tosh]

No. You ever tinker around with your own kids brains?

[Dr. Roy Sillitoe]

I used to kind of feel behind their heads, you know, pretending that I could feel and massage the cerebellum. It may have helped, but. But I definitely did. I wonder what's in there.

[Daniel Tosh]

Where are you? On parents being able to choose their child's features, like eye, hair color, height, weight, sex.

[Dr. Roy Sillitoe]

I think that's crazy. That's crazy. I. I don't know if we can get there. Oh, I think that's. That's a tough one.

[Daniel Tosh]

Everybody's on the show gets a gift. It's just stuff around my house. You live in Texas and I know you have PhD, so here's a putter. Oh, my golf.

[Dr. Roy Sillitoe]

I've never golfed. I will now.

[Daniel Tosh]

No, but this. This putter right there is a former PGA player, Mickey demorat. He is my nephew. He's on. Was on the p. He used that for a bit.

[Dr. Roy Sillitoe]

Wow.

[Daniel Tosh]

Yeah.

[Dr. Roy Sillitoe]

Thank you.

[Eddie Gosling]

Thank you.

[Daniel Tosh]

I don't know what. Why I have this, but it's. It's for your. 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. Get rid of that.

[Dr. Roy Sillitoe]

I'll put it in mine. Thank you.

[Daniel Tosh]

That's how the game works. Look at that. You put it on the floor right away. Thank you. Talk about your family's hatred for the late, great Kobe Bryant.

[Dr. Roy Sillitoe]

Oh, no, we love Kobe Bryant.

[Daniel Tosh]

Oh, you do?

[Dr. Roy Sillitoe]

We just don't like black Mambas.

[Daniel Tosh]

You don't like black mambas? My bad. That's bad intel.

[Dr. Roy Sillitoe]

Kobe Bryant's amazing.

[Daniel Tosh]

You're fine with Kobe. You hate black mambas.

[Dr. Roy Sillitoe]

Yeah, we don't like black mambas in my family. My dad's youngest brother was killed by a black mamba.

[Daniel Tosh]

Can he do anything? How long do you have?

[Dr. Roy Sillitoe]

You don't have much time. You have minutes.

[Daniel Tosh]

And you don't feel their bites as much because their teeth are so thin.

[Dr. Roy Sillitoe]

That's right. And they strike several times. On every strike, you'll have multiple penetrations.

[Daniel Tosh]

What are you supposed to do to just not play as a child?

[Dr. Roy Sillitoe]

I mean, that's, that's living in the bush in Africa. You know, there's snakes, lions, elephants. That, that's, that's, that's how it is living out there.

[Daniel Tosh]

Well, I mean, I tell you what, that's a pretty big strike.

[Eddie Gosling]

Yeah, yeah.

[Dr. Roy Sillitoe]

I mean, the story is if, if you see a black mamba, well, you're not going to tell the story about it.

[Daniel Tosh]

I don't like that. Describe your dream scenario of what this electric stimulation technology will be able to do in 10, 20 years.

[Dr. Roy Sillitoe]

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 this is, 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 gonna 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 gonna 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 therapy that actually fixes your brain communication, activates certain genes, dampens the bad genes, and you walk out.

[Daniel Tosh]

And that's obtainable in 10 years, 20 years.

[Dr. Roy Sillitoe]

20 years maybe. 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.

[Daniel Tosh]

Okay, this one's for Eddie. I'll Give Eddie one. Could Jesus 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 how we start there.

[Dr. Roy Sillitoe]

You know, it's wild. But that is actually a trivial experiment to do that is very possible.

[Daniel Tosh]

Scary enough, you get some funding in Texas, you start creating rat Jesus.

[Eddie Gosling]

There you go. We're in.

[Daniel Tosh]

Thank you for being here, Dr. Roy Sillitoe. Sillitoe.

[Dr. Roy Sillitoe]

Thank you.

[Daniel Tosh]

That's your last name?

[Dr. Roy Sillitoe]

That is my last name.

[Daniel Tosh]

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?

[Hadley]

No.

[Daniel Tosh]

You don't? No. Do you like Kiawah Kiawah?

[Dr. Roy Sillitoe]

Yeah.

[Daniel Tosh]

You guys love to go there? Heading up to South Carolina. You guys gotta come. It's like other places. How are you feeling right now? How's your health?

[Hadley]

Good.

[Daniel Tosh]

When's the last time you were sick?

[Hadley]

Three years.

[Daniel Tosh]

Three years since you were in the hospital?

[Hadley]

Yeah.

[Daniel Tosh]

I mean this is like record stress. What is magic medicine?

[Hadley]

That helps me.

[Daniel Tosh]

It helps you?

[Dr. Roy Sillitoe]

Yes.

[Daniel Tosh]

Uh huh. Magic medicine is what. What old Dr. Roy's working on.

[Hadley]

Yeah.

[Daniel Tosh]

Yeah. Okay. Hadley, thank you for being on my show.

[Hadley]

You're welcome.

[Daniel Tosh]

All right, have a good day. Let's go surfing. Oh, those are some fancy bracelets. You got a doggy? Yeah. I had a duck once. 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 was. Flew away or was eaten, I don't know, just left. I was like, I'm not gonna stay here in this tiny little thing. Didn't have a roof over it. It was a bad gift. Paw show. 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 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, eh? 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. Got to go see the family. Let's do some plugs. Patreon.com tosshow for some extra content. The stuff that was too hot for the Internet. My first farewell tour. Tickets are on sale now. We're heading out this week, Ed.

[Eddie Gosling]

We're going.

[Daniel Tosh]

Oh, we got so many pizza spots to hit up in Indiana.

[Eddie Gosling]

Who knew Indiana was so full of pizza spots?

[Daniel Tosh]

Or is your buddy going to be at the show?

[Eddie Gosling]

I think he told me he's already got tickets to two shows in the Midwest.

[Daniel Tosh]

2. 2. You only need to get tickets to one show and then just remember the material.

[Eddie Gosling]

Yeah.

[Daniel Tosh]

Oh, boy. Well, the pressure is on. I cannot. There's no pressure on me. Measures on you and your buddy Hutch.

[Eddie Gosling]

Hutch. Maybe he'll join us for one of these pizzas.

[Daniel Tosh]

I'll buy. I'll buy Hutch a slice. I'm not gonna get him a whole pizza.

[Eddie Gosling]

Get him a pizza. A whole pizza, and we just leave. He sits there with a whole pizza.

[Daniel Tosh]

No, I'm not giving him a whole. He can have a slice.

[Eddie Gosling]

A slice.

[Daniel Tosh]

Now, I've been hearing about that Stromboli pizza.

[Eddie Gosling]

Just. It seems like a pizza folded up. Right?

[Daniel Tosh]

No, it's got to be something special. It's gotta be.

[Eddie Gosling]

But I don't think it's.

[Daniel Tosh]

All right.

[Eddie Gosling]

Who knows? We'll try it.

[Daniel Tosh]

Tossshowstore.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?

[Eddie Gosling]

Here we go. This is from Elizabeth Gleaton, 1598.

[Daniel Tosh]

Oh, Elizabeth.

[Eddie Gosling]

Yeah. Thanks also to Daniel Tosh for highlighting non celebrities who do important work and jobs.

[Daniel Tosh]

Well, you're welcome. I appreciate your comment.

[Eddie Gosling]

There you go.

[Daniel Tosh]

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.

[Eddie Gosling]

Oh, yeah, something a little thicker.

[Daniel Tosh]

Oh, yeah.

[Eddie Gosling]

Bring it. Bring it. Commenters. All right, here's the other one.

[Daniel Tosh]

Next one.

[Eddie Gosling]

You should know better. V2, first time I gave up on a toss show interview, I just can't do it.

[Daniel Tosh]

Oh, they didn't like the interview and they. What show was that from? That's an important piece of the information here.

[Eddie Gosling]

Yeah, I don't have that. I should. I gotta find that.

[Daniel Tosh]

I mean, because that could have been from our travel agent. A lot of people felt the same way.

[Eddie Gosling]

Right.

[Daniel Tosh]

But if that was for my wife, you know, what am I to do? I live with the person. I love the person. And now I gotta be like, oh, well, I gotta get rid of her.

[Eddie Gosling]

We don't even know which one to go back and look at to take the notes and see what we can do better.

[Daniel Tosh]

Well, the good thing is next week it'll be somebody new sitting across from me. See you next week. This episode of Tosh show is brought to you by Progressive Insurance. Do you ever think about switching insurance companies to see if you could save some cash? Progressive makes it easy to see if you could save when you bundle your home and auto policies. Try [e-mail] Progressive Casualty Insurance Company and affiliates. Potential savings will vary. Not available in all states. The Global Gaming League is presented by Atlas Earth, the fun cashback app.

[Howie Mandel]

Hey, it's Howie Mandel and I am inviting you to witness history as me and my How We do it gaming team take on Gilly the king and wallow. $267 million gaming in an epic Global Gaming League video game showdown plus a halftime performance by multi platinum artist Travy McCoy. Watch all the action and see who wins and advances to the championship match right [e-mail] that's globalgamingleague.com in partnership with Level Up Expo.