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Armchair Expert with Dax Shepard

David Fajgenbaum (on repurposing medicine)

26 Nov 2025

Transcription

Chapter 1: What is discussed at the start of this section?

0.25 - 20.426 David Fajgenbaum

Wondery Plus subscribers can listen to Armchair Expert early and ad-free right now. Join Wondery Plus in the Wondery app or on Apple Podcasts. Or you can listen for free wherever you get your podcasts. Welcome, welcome, welcome to Armchair Experts on Experts. I'm Dan Shepard, joined by Lily Padman.

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20.446 - 20.806 Unknown

Hi.

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21.187 - 38.273 David Fajgenbaum

Today we have David Fagenbaum, who is a physician, scientist, and best-selling author. His books are Chasing My Cure and We Get It. This is an incredible story of a guy who cured his own disease that he was dying of, actively dying of.

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38.371 - 43.436 Unknown

And working hard on curing others. This is wild and so cool.

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43.597 - 48.101 David Fajgenbaum

Very cool. And he was a football stud. Talk about mixed messages.

48.482 - 51.985 Unknown

And he went to college with a perfect 10. Charlie, as you'll hear.

52.166 - 73.251 David Fajgenbaum

Yes. Also, if you're moved by this episode, which I think you will be, and you want to donate to EveryCure, please go to www.everycure.org. Please enjoy David Fagenbaum. Armchair Expert is proud to have Alexa Plus as our presenting sponsor. The all-new Alexa Plus is your smart, proactive AI assistant.

Chapter 2: What was David Fagenbaum's experience with football and education?

73.672 - 86.951 David Fajgenbaum

Just chat naturally about anything and watch your to-do list disappear. It learns your style and anticipates what's next across Echo, Fire TV, and more. Learn more at Amazon.com slash new Alexa.

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88.653 - 90.636 Unknown

He's an Armchair Expert.

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102.074 - 111.391 Dax Shepard

I was just sharing with Monica that Charlie.

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111.491 - 115.459 David Fajgenbaum

Yes, it's so exciting. I know, I just learned this mere minutes ago myself.

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115.599 - 137.467 Unknown

We just FaceTimed him. Oh, you did? Yeah, we FaceTimed him, said hi. Were you recording, I hope? Well, we were over in the corner. Oh, that's not going to work. So, not really. But yeah, since we weren't recording, David is good friends with Perfect Ten. We call him Perfect Ten Charlie on this show. You can't be surprised. I'm not surprised at all. Georgetown. Georgetown, very good school.

137.527 - 139.69 Unknown

Very prestigious. I mean, David's gone to all the good schools.

139.91 - 144.796 David Fajgenbaum

He really has. He's gone to too many good schools. It's almost like a sickness. At some point.

144.816 - 145.657 Unknown

Ding, ding, ding.

145.677 - 146.097 David Fajgenbaum

Tell me.

Chapter 3: How did David's mother's illness impact his career path?

1079.077 - 1088.671 Dax Shepard

I was doing anything I could to stay awake. So I took a medical school exam and then I'm sure I got like the worst grade ever. I never got my score back. And I went down the hall to the emergency department and they did blood work.

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1088.691 - 1092.857 David Fajgenbaum

Really quick, from feeling the inflamed lymph nodes. Two weeks. Two weeks. Okay, two weeks.

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1092.877 - 1107.801 Dax Shepard

Okay, so walking down the hall. I even remember when I was taking this med school exam, I was like, is the answer A or B? And then I remember in my brain, I thought to myself, I'm like, it doesn't matter because I'm about to die. And I'm like, why did I think that? I'm about to die, what? And so like I finished the exam, I walked down the hall to the ER. Can we take one second right there?

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1107.981 - 1123.79 David Fajgenbaum

That is a gift to have those moments a few times in your life to experience a right sizing of what's important. Just a few times in your life and hopefully it doesn't kill you. But I've had a couple of those, right? Where it's like, oh, right. I don't give a flying fuck about all the stuff I thought I cared about. It's a unique feeling.

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1123.991 - 1126.896 David Fajgenbaum

Like for you to say you don't give a shit how you did on the test is really profound. Yeah.

1126.876 - 1137.473 Dax Shepard

And I think it's an important feeling for us to share with other people because the important thing is to start putting your mind in that place before you have to experience it yourself. Like don't wait until you're 80 years old and then you're like, oh crap, I wish I had thought this.

1137.533 - 1138.775 Unknown

But I don't know that you can get.

1138.816 - 1140.278 Dax Shepard

But yeah, I used to have to be there.

1140.298 - 1143.984 Unknown

I don't know if you could borrow it. I think you just have to experience it, unfortunately.

Chapter 4: What role does folate play in brain development?

2859.772 - 2878.409 Dax Shepard

So a portion of kids that are nonverbal and or have other neurodevelopmental challenges, often speech delays, they actually can have a antibody against the folate receptor. So folate is important for brain development. And in order to get folate into your brain, you need this receptor to be functioning. But if you have an antibody against it, basically the vitamin doesn't cross into the brain.

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2878.749 - 2894.348 Dax Shepard

These kids can have what's called a cerebral folate deficiency. And so interestingly, there's a derivative of folate called folinic acid. It was made for people that are on methotrexate chemotherapy, and it's been around for decades. but that derivative of folate can actually bypass this blockage at the receptor and can get into the brain.

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2894.508 - 2907.612 Dax Shepard

Can leapfrog this whole... Yeah, there's something called the RFC, which is a channel right next to the folate receptor. And so if the folate receptor is blocked, but if you give the derivative of folate, it can go through this channel. So basically leapfrog, get in the brain. And that was a really important discovery that humans made.

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2907.652 - 2921.792 David Fajgenbaum

Let me ask you really quick, because So that makes total sense. There's this thing inhibiting this vitamin required for this part of the brain to function. But in the absence of that, wouldn't that portion have already been so atrophied it couldn't be brought back? Or it's just there and it needs that as fuel?

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2922.333 - 2931.005 Dax Shepard

It's a good question. We don't know the answer to it. All we know is that work's been done to show that some of these kids have too little folate. We know that the reason they have too little folate is because of the antibody receptor.

2931.025 - 2939.336 Dax Shepard

And then the really interesting thing is that there have been multiple clinical trials now, all relatively small, that have shown that giving this derivative folinic acid can improve verbal communication communication to these kids.

2939.536 - 2940.477 Unknown

Wow. Is it just a pill?

2940.557 - 2942.238 Dax Shepard

It's just a pill. Yeah. Give the example.

Chapter 5: How can folinic acid help nonverbal children?

2942.359 - 2944.981 Dax Shepard

One kid was nonverbal for five years. That's Ryan.

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Chapter 6: What are the implications of using AI in medicine?

2945.041 - 2960.414 Dax Shepard

Ryan was basically nonverbal for five years. He could do something called echolokia, where if someone said something to him, he could repeat it back to them, but he could never actually share his own. He'd never made an executive communication where he made the decision. He had receptive communication. So he had a lot of things in his mind that he wanted to say, but he couldn't say them.

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2960.695 - 2966.66 Dax Shepard

Within two weeks starting Lucavorin, he told his dad for the first time ever a statement. And he said, Daddy, I love you.

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2966.68 - 2968.103 Unknown

Oh. Fuck, I'm dead.

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2968.283 - 2972.893 Dax Shepard

That would have killed him. I was like, I cried for the next 15 minutes.

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2972.914 - 2973.535 David Fajgenbaum

I couldn't do anything.

2973.555 - 2973.876 Unknown

Can you imagine?

Chapter 7: How does Every Cure address the financial issues in drug repurposing?

2973.956 - 2975.138 Dax Shepard

He couldn't even leave the house.

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2975.239 - 2980.53 David Fajgenbaum

Yeah, my kid's first sentence would be like, I want to go to Target, I think.

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2980.891 - 2981.813 Unknown

Because he's been stuck wanting to stay there.

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2981.793 - 2993.628 David Fajgenbaum

And also, like, should Ryan have had behavioral issues over the years? Of course, if you had all your thoughts and you couldn't fucking get them out to you, I would rage. Could you imagine? But there's been multiple success stories.

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2993.708 - 3007.425 Dax Shepard

Multiple success stories. And actually, there's another patient, Mason, who within three days of starting it, he said his first word. And just thinking about what my kids would say, his first word was more. And I feel like that's all my kids would ask me for more. And I was like, that's exactly what my kids would say.

3007.445 - 3008.306 Unknown

More, more, more, more, more.

3008.326 - 3009.387 Dax Shepard

That's very human. Yes, me too.

3010.126 - 3012.91 Unknown

Oh my gosh, that's so incredible.

3012.991 - 3027.173 Dax Shepard

Yeah. And so like, this is why we wanted to start EveryCure because there's things that are out there. And I love that EveryCure and AI can help us discover new treatments. And I can share about some that we've discovered. Literally, it's like, oh, wow, this is never been used. That's amazing. But sometimes it just uncovers what us humans know about, but we just don't put into practice.

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