David Fajgenbaum (on repurposing medicine)

David Fajgenbaum (Chasing My Cure, Every Cure) is an immunology researcher, professor, and author. David joins the Armchair Expert to discuss being recruited to play football at an assortment of Ivy League schools before ending up at Georgetown, the promise he made to his mother to pursue medicine before she passed away, and starting a foundation in his mom’s honor to help college students with grief. David and Dax talk about the sudden onset of symptoms that meant his liver and kidneys were shutting down, gaining 100 pounds of fluid almost overnight, and nearly dying multiple times amid a diagnosis of Castleman disease. David explains the decision to approach his illness with off-label drugs, putting himself into full remission with a drug used to prevent transplant rejections, and the current mission with non-profit Every Cure to treat other inflammatory diseases with existing medicine. Follow Armchair Expert on the Wondery App or wherever you get your podcasts. Watch new content on YouTube or listen to Armchair Expert early and ad-free by joining Wondery+ in the Wondery App, Apple Podcasts, or Spotify. Start your free trial by visiting wondery.com/links/armchair-expert-with-dax-shepard/ http://www.wondery.com/links/armchair-expert-with-dax-shepard/ now. See Privacy Policy at https://art19.com/privacy and California Privacy Notice at https://art19.com/privacy#do-not-sell-my-info.

Speaker names marked ? are inferred from speaking time and the show’s known hosts — they are not voice-verified.

• 0:00Dax Shepard?

  Welcome, welcome, welcome to Armchair Experts on Experts. I'm Dax Shepard, joined by Lily Padman.

• 0:06Speaker 01

  Hi.

• 0:07Dax Shepard?

  Today, we have David Faganbaum, who is a physician, scientist, and bestselling 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.

• 0:24Speaker 01

  And working hard on curing others. It's, this is wild and so cool.

• 0:29Dax Shepard?

  Very cool. And he was a football stud. Nah, we're talking about mixed messages.

• 0:34Speaker 01

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

• 0:38Dax Shepard?

  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 Faganbaum. Armchair Expert is proud to have Alexa Plus as our presenting sponsor. The all-new Alexa Plus is your smart, proactive AI assistant. 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/newalexa. We get support from Quince.

• 1:16Speaker 01

  I have to say, I am so ready for fall. I want sweaters. I've been craving a true crisp morning where I actually need a jacket. I can't wait.

• 1:25Dax Shepard?

  I'm fully there. The second it dips below 70, I'm like, this is my season. Give me the layers, give me the boots, give me a reason to wear something other than a t-shirt. And honestly, that's why I love Quince, because fall is when your wardrobe actually has to show up. And everything at Quince is 50 to 80% less than similar brands. We're talking 100% Mongolian cashmere sweaters, starting at $60.

• 1:48Speaker 01

  $60. $60 for cashmere that you'd expect from a luxury brand without the luxury price tag. It's amazing. Gets me every time. It really shouldn't be real, but it is, because they go straight to the factories, they skip the middlemen, and they just hand you the savings. The stuff isn't trendy, it's the kind of pieces you grab over and over because they work every time.

• 2:06Dax Shepard?

  The 100% Mongolian cashmere sweaters for me are it. When I look at Steve This man owned a couple of sweaters he wore all the time and he looks iconic.

• 2:15Speaker 01

  It's a uniform.

• 2:16Dax Shepard?

  Mm hmm.

• 2:16Speaker 01

  And Quince isn't just about the clothes. They have hotel quality bedding, cookware, bath essentials, thoughtfully designed furniture. You can really go there and outfit your entire apartment or house. So if you're in need of any kind of fall refresh at home, too, same quality, same attention to detail for every corner of your life.

• 2:34Dax Shepard?

  Find your next fall favorites at Quince. Download the Quince app for app exclusive offers or go to quince.com. Get free shipping on your order and 365 day returns. Now available in Canada and the UK too. And when Quince asks where you heard about them, let them know it was Armchair Expert. It's the best way to support the show.

• 3:11Dax Shepard?

  How are you?

• 3:13Speaker 02

  Good to meet you.

• 3:15Dax Shepard?

  I was just sharing with Monica that Charlie.

• 3:17Speaker 01

  Yes, it's so exciting.

• 3:19Dax Shepard?

  I know, I just learned this mere minutes ago myself.

• 3:21Speaker 01

  We just FaceTimed him.

• 3:22Dax Shepard?

  Oh, you did?

• 3:23Speaker 01

  Yeah, we FaceTimed him, said hi. Well, we were over in the corner.

• 3:28Dax Shepard?

  That's not gonna work.

• 3:30Speaker 01

  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.

• 3:37Dax Shepard?

  You can't be surprised. I'm not surprised at all. Georgetown.

• 3:41Speaker 01

  Georgetown, very good school.

• 3:42Dax Shepard?

  Very prestigious.

• 3:43Speaker 01

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

• 3:45Dax Shepard?

  He really has.

• 3:46Speaker 02

  He's gone to too many good schools.

• 3:48Dax Shepard?

  It's almost like a sickness at some point.

• 3:50Speaker 01

  Ding ding ding.

• 3:51Dax Shepard?

  Tell me.

• 3:51Speaker 01

  Because David had a sickness.

• 3:53Dax Shepard?

  Oh.

• 3:55Speaker 01

  Hello.

• 3:55Dax Shepard?

  I didn't realize we're at the making light of a party. Yeah, but that's great. We should start there. Welcome, how are you?

• 4:01Speaker 02

  Doing well, thank you. How are you doing?

• 4:02Dax Shepard?

  Wonderful. So yeah, as Monty was just saying, I was working out appropriately to receive a text from Charlie and I was like, ah, Formula One race, yes, expected, expected.

• 4:11Speaker 01

  Oh, sure.

• 4:11Dax Shepard?

  I think you're interviewing my friend Dave. And I was thinking, how could he possibly know this doctor?

• 4:16Speaker 01

  Right.

• 4:17Dax Shepard?

  And then, of course, you were his quarterback.

• 4:19Speaker 02

  That's right, we play football. Georgetown and you guys are a couple of the people who actually know Georgetown as a football team. A lot of people don't know about our team.

• 4:25Dax Shepard?

  I don't know if without Charlie I would have known and then also even if I knew I wouldn't have guessed it was division one.

• 4:30Speaker 01

  I didn't know. I went to Georgia, so.

• 4:34Speaker 02

  Yeah. And you know, we have like a bulldog mascot, but we had to change from being the Georgetown Bulldogs because there's the Georgia Bulldogs.

• 4:40Speaker 01

  Too close.

• 4:41Speaker 02

  So were the Georgetown Hoyas. I don't know if you've heard this.

• 4:43Dax Shepard?

  Oh, yeah. Go Hoyas.

• 4:44Speaker 02

  Yeah, go Hoyas.

• 4:45Speaker 01

  What's a Hoya?

• 4:45Speaker 02

  It means what in Greek and so apparently it came about.

• 4:50Speaker 01

  Exactly.

• 4:50Speaker 02

  Yeah, there were some priests that were screaming Hoya Sax, which means what rocks. Then people would say Georgetown and

• 4:55Speaker 01

  Oh, wow.

• 4:56Speaker 02

  All of a sudden we're the Hoyas, which means we're the whats.

• 4:58Dax Shepard?

  And so were you guys pals pals or?

• 5:00Speaker 02

  We were, yeah.

• 5:01Dax Shepard?

  You were?

• 5:01Speaker 01

  Yeah, they're good friends.

• 5:03Dax Shepard?

  They're best friends.

• 5:04Speaker 01

  So sim.

• 5:05Dax Shepard?

  But Charlie will be the first to admit he ran with a real meathead clique within the football program. Were you immersed in that?

• 5:13Speaker 02

  If you open up the book, I showed Monica a picture. Open it up and go to this middle picture.

• 5:17Dax Shepard?

  I've already looked at your body. If that's where we're going with this.

• 5:20Speaker 02

  I know your body very well. I don't look anything like I look like now. I mean, I've fully embraced dad bod these days.

• 5:25Dax Shepard?

  Oh, we in the middle?

• 5:26Speaker 02

  Oh, yeah, the very middle. Um, there's a picture there.

• 5:28Dax Shepard?

  I mean, I know this picture by heart. I love a great body.

• 5:31Speaker 02

  But the point being, that's what I looked like. So yes, you could have called me a meathead back then, but I was pre-med and I had intentions to be a doctor.

• 5:37Speaker 01

  Yeah.

• 5:37Dax Shepard?

  Yeah, and.

• 5:39Speaker 01

  What a catch. Can you believe? I mean, if I'm in college and there's a pre-med.

• 5:45Dax Shepard?

  Oh, forget it.

• 5:46Speaker 01

  Man who looks like this.

• 5:48Speaker 02

  My poor wife, she started dating me when I looked like that and then she stuck with us. It's rough.

• 5:52Dax Shepard?

  He was a lineman. Yeah, he was a defensive.

• 5:53Speaker 02

  He was a tight end. He was a tight end, yeah. I used to throw footballs to Charlie.

• 5:57Dax Shepard?

  Oh, and you could count on him?

• 5:59Speaker 02

  I always, always.

• 6:01Dax Shepard?

  I would imagine that is a special relationship between the quarterback and the tight end.

• 6:04Speaker 02

  Tight end, especially because they're the one position in the field that you both were throwing passes to and they're also blocking for you, right? Like you have a special relationship with your offensive line because your life is sort of in their hands.

• 6:12Dax Shepard?

  Gronk was a tight end?

• 6:13Speaker 02

  Gronk was a tight end. That's right.

• 6:15Dax Shepard?

  So of course TB 12 and Gronk are besties. That makes sense. How are Travis Kelsey and?

• 6:20Speaker 02

  Oh, and Mahomes?

• 6:21Dax Shepard?

  Mahomes, are they?

• 6:22Speaker 01

  They're good friends. They're very good friends.

• 6:24Dax Shepard?

  Okay, okay. Well, let's start in Raleigh, North Carolina, because your dad was also a physician.

• 6:29Speaker 02

  That's right. That's right.

• 6:30Dax Shepard?

  What kind of physician was he?

• 6:32Speaker 02

  Orthopedic surgeon.

• 6:33Dax Shepard?

  Ironic.

• 6:34Speaker 02

  Yeah.

• 6:35Dax Shepard?

  Because I was gonna ask you, how did your physician father feel about you playing football in the first place? But I would imagine even compounded by this being an orthopedic surgeon.

• 6:44Speaker 01

  Like that he wouldn't want it?

• 6:45Dax Shepard?

  Well, he's probably observed a lot of injuries.

• 6:46Speaker 02

  Well, that's true, but also he was an orthopedic surgeon for the NC State football team. So he was like taking care of people that were playing football. And that sort of led to why I fell in love with football so much.

• 6:56Dax Shepard?

  Right, because you were hanging.

• 6:58Speaker 02

  Exactly.

• 6:58Dax Shepard?

  Exactly. Okay, and were you a standout in high school? What were the challenges? Did you have a hard time putting on weight?

• 7:05Speaker 02

  I'm like an okay athlete, but I work really, really hard.

• 7:10Dax Shepard?

  But David, I have to tell you something, every athlete says that. I finally want one to say like, I'm a fucking physical phenom, I hit the genetic lottery.

• 7:16Speaker 02

  Charlie Curtis.

• 7:17Dax Shepard?

  Oh no, he'll tell you he worked so hard.

• 7:20Speaker 01

  No, he says he's the best.

• 7:22Speaker 02

  Too hard work.

• 7:24Speaker 01

  He says he's the best athlete. One time, we were all at a vacation and the men were playing horseshoes. And my friend Jess, who is very athletic, but has not done athletics in a long time. And Jess was kind of dominating at horseshoes and everyone was getting very upset.

• 7:44Dax Shepard?

  It was confronting their stereotypes, to say the least.

• 7:47Speaker 01

  And I said, Jess is the best athlete here. And Charlie did not like that.

• 7:53Speaker 02

  Charlie's competitive, for sure. So to give a sense for how crazy I was about working, I had posters all over my wall as a 10-year-old. They were like tracking how fast I could run, how far I could throw. I was totally, totally obsessed and just worked like crazy.

• 8:08Dax Shepard?

  Your dad must have loved this. If I had a little guy and he was taking something this serious and working so hard, it would have just made my heart explode.

• 8:14Speaker 02

  I think both my parents, they did love it, but I think they also were like a little concerned. He's really, really focused on this thing, like, is this too much?

• 8:21Dax Shepard?

  Well, my concern would be, boy, he's given in his whole life. If it doesn't work out in some capacity, he's gonna be heartbroken.

• 8:26Speaker 02

  Exactly.

• 8:26Dax Shepard?

  Yeah, but it worked out. You did get recruited to play at Georgetown.

• 8:30Speaker 02

  That's exactly right.

• 8:31Dax Shepard?

  Did you have other offers, other schools?

• 8:33Speaker 02

  I did, I was recruited by Ivy League schools, so Yale and Cornell and Georgetown. And then a couple other smaller schools in the North Carolina, South Carolina region too.

• 8:40Dax Shepard?

  Did you pick Georgetown for some kind of family tradition?

• 8:42Speaker 02

  There were a few things. Georgetown had this pre-health program, which wasn't just a typical pre-med where you're taking basic science, but it actually had, where you actually could learn about the human body and learn about health and disease. And that was interesting to me at the time. And then I loved the quarterback coach at Georgetown. Joe Moorhead is amazing. He went on to be the head coach at Mississippi State and coordinator at Penn State. And it was his first job as a Georgetown. I was like, oh, my God, this guy's amazing. He's going to be incredible, and he is incredible.

• 9:05Dax Shepard?

  And when you went there, you were already going to do medicine, yeah?

• 9:09Speaker 02

  When I went there, I was really interested in sports medicine. I was really interested in like exercise and diet and nutrition, all that sort of stuff.

• 9:15Dax Shepard?

  So does mom's glioplastoma change courses here?

• 9:19Speaker 02

  Changed everything. It was just a couple of weeks after I got to Georgetown was when my dad called and told me that my mom had brain cancer. And I immediately went home to be with her. And just a couple of days later, she had brain surgery. It was heartbreaking.

• 9:32Dax Shepard?

  So it was operable? Rarely can you operate on them, yeah?

• 9:35Speaker 02

  So this was operable. It was in the front left part of her brain. And so it was in a particular location where they open up your skull and they actually wake you up once they've opened it up. And the reason they do that is because they want to start cutting out tumor, but they don't want to cut out too much because then you're like, you won't be able to speak. And so they did this surgery. It took four and a half hours. And my sisters, my dad and I were just terrified. And I remember they said she made it through surgery and we're so happy. We're going to go back to see her. And I remember we're like crying because we're so happy. Just there's so many emotions. And I told my sisters and I was like, we've got to stop crying. Like, let's be strong for mom. And we go back to see her. And I'll never forget this. She had a wrap around her head and she had this bulb coming out of it. It was basically like draining the fluid. She was sort of sitting up. We just didn't know what to say.

• 10:18Speaker 02

  And we walked in and my mom pointed to her head and she looked at us and she said, Chiquita Banana Lady. And we just like burst into laughter. She was making this joke for us that like the wrap and the bulb, like that she looked like the Chiquita Banana Lady. And I loved it so much because she just had a four and a half hour brain surgery. She's brain cancer. But what's the first thing she's thinking about? What can she say to make us laugh? We're crying and we're snot crying. And we're like, our mom's still here. First off, she was speaking. We didn't know if she'd be able to.

• 10:47Dax Shepard?

  Yeah, yeah, yeah.

• 10:48Speaker 02

  And then she was trying to make that joke. It was just everything.

• 10:49Dax Shepard?

  Do I have Bader Minehoff? It feels like I've heard an inordinate amount of women in the last 10 years get this glioplastoma. Is it asymmetric to women?

• 11:00Speaker 02

  I haven't heard about it being more common in women, but it does feel like it's just getting more common.

• 11:04Dax Shepard?

  We know like three different people in our circle.

• 11:07Speaker 01

  Related to one person.

• 11:10Dax Shepard?

  Well, one person knows three people and we know that person.

• 11:12Speaker 01

  Yeah. And one of the people is a man who was affected by her. But yeah.

• 11:18Dax Shepard?

  So there's no weird gender thing happening with that?

• 11:21Speaker 02

  But it's heartbreaking. It's just one of the worst out there.

• 11:24Dax Shepard?

  So the surgery, what did that buy her?

• 11:26Speaker 02

  It bought her about a year of clean scans.

• 11:29Dax Shepard?

  Was it followed by radiation?

• 11:30Speaker 02

  Radiation and chemotherapy. And this is back in 2003, 2004. She either came up to Georgetown every weekend, or I went home every weekend to North Carolina to see them. So got a really special time with them. And I remember about nine months in, when they did the first big scan after it's been a while and it was clean. That was one of the first times where I just had the most intense tears of joy of my life. It was just sort of like, oh, my gosh, a clean scan. This is amazing. But then it was just a few months later is when it started to grow back. And she passed away 15 months after she got sick.

• 11:58Speaker 01

  Oh, man. So sad.

• 12:00Dax Shepard?

  Yeah, that's fucking rough. So you were in your sophomore year?

• 12:03Speaker 02

  I'm over a sophomore year.

• 12:04Speaker 01

  You're in college.

• 12:06Dax Shepard?

  Yeah. Do you see a dip in performance in all categories for a minute? Or do you get psycho type A and work even harder to ignore it all?

• 12:13Speaker 02

  More than a lot. So part of it was the moment my mom got sick with brain cancer. All those posters I had about football and all the thoughts, that was out of my mind. And it was like, I want to dedicate my life to finding treatments for people like her. I'm not interested in sports medicine. I'm not even really interested in football right now. I just want to be a doctor because I want to dedicate my life to helping patients like her. If I'm going to be at school while my mom's going through this, like I'm going to lock in and I'm going to become a doctor and help people like her. And a couple of weeks before she passed away, I promised her that. That was the last thing I ever told her.

• 12:42Dax Shepard?

  Yeah.

• 12:43Speaker 02

  I said, Mom, I'm going to be okay and I'm going to dedicate my life to trying to find treatments for patients like you.

• 12:48Dax Shepard?

  Yeah. What did she say? So I have kids, you have kids. If one of my little girls says to me, I go, oh, honey, do not hurt in yourself with me at all. You go have whatever life you want. You don't know.

• 12:59Speaker 02

  Because of the brain tumor and the part that was in, she didn't have too many words left. But it still hits me today. One of the things that she could say and the thing that she said was unconditional love. Again, she didn't have too many words. And so like that was something she could say. She started crying. I cried.

• 13:12Dax Shepard?

  Yeah.

• 13:13Speaker 01

  Wow, how special.

• 13:14Dax Shepard?

  Well, dude, you gave her the ultimate gift, which is I only hope for one thing in my life. And if I get me looking at my little girls when I die. I'm gonna be like stoked.

• 13:20Speaker 02

  Yeah.

• 13:21Dax Shepard?

  That's as good as it gets.

• 13:22Speaker 02

  It is.

• 13:23Dax Shepard?

  Okay, so you get hardcore about medicine. You graduate from Georgetown.

• 13:28Speaker 02

  That's right.

• 13:29Dax Shepard?

  You go to Oxford. What's this detour? You get your masters in Oxford?

• 13:33Speaker 02

  Yeah, during my time at Georgetown, I became obsessed with medicine and cancer and cancer treatment, cancer prevention, and I learned that there was a program at Oxford focused on health promotion and disease prevention, and they were particularly focused on heart disease prevention. But there was data coming out around that time that diet, physical inactivity, and smoking can actually all contribute to cancer risk. And so this idea that like, well, maybe I could go study with these people who are focused on heart disease prevention, we could apply it to cancer prevention.

• 14:01Dax Shepard?

  And did you like it?

• 14:02Speaker 02

  I did. I loved the academic part of it. I have to admit, I didn't mesh as well with Oxford students as maybe I did with my buddies from Georgetown or from Penn.

• 14:11Dax Shepard?

  Whatever cultural gap.

• 14:12Speaker 02

  It's funny, I played football at Oxford. They have an American football team.

• 14:15Dax Shepard?

  Were you ridiculously good compared to everyone?

• 14:17Speaker 02

  It was really fun. It was really fun.

• 14:18Dax Shepard?

  You were a sandbag.

• 14:19Speaker 02

  But what was cool is that it was a joint program between Oxford University and Oxford Brooks. Oxford Brooks is the local state school that's right next to Oxford, and I just got along so much better with the guys from the Brooks side of things.

• 14:29Speaker 01

  Oh, interesting. Can you be objective enough to answer if you were exceptional at Georgetown? Or if everyone at Georgetown is like you?

• 14:38Speaker 02

  In terms of?

• 14:39Speaker 01

  Achievement?

• 14:40Speaker 02

  The biggest thing that I would say is that Georgetown has this really special focus on helping other people. Like, the motto is men and women for others. And I think that that was the perfect place for me to be at that moment in my life, to be in an environment where literally the walls say like, men and women for others. Take what's gone on to you and help other people. That was the perfect environment because I shared one part of the promise to my mom with you all, and that was that I would become a doctor. The other promise is I told her I was gonna create an organization in her memory. Her name was Anne Marie Faganbaum. Her initials were AMF. And I was like, I'm gonna call it AMF. I don't know what it's gonna stand for.

• 15:10Speaker 01

  Wow.

• 15:11Speaker 02

  But it's gonna be for grieving college students. Because I was really struggling with this anticipatory grief. And so we started at AMF and then ended up spreading that to other college campuses. I think if I was at any other college campus, I don't know if that immediate, I'm going through a lot of pain, I'm gonna now create something to help other people. I don't know if I would have done that anywhere else. So I think Georgetown was the right environment for that.

• 15:29Dax Shepard?

  Now David, I'm a teeny bit suspicious though that I don't know if you were, were you dealing with it? Do you think you were dealing with it?

• 15:34Speaker 02

  Dealing with my grief?

• 15:35Dax Shepard?

  With your grief?

• 15:36Speaker 02

  No, I think that the way that I decided to start dealing with my grief was it's called instrumental grieving, where like you create something and you pour it into that thing. And this is actually something that a lot of men do when they deal with grief. They channel it to something. I created AMF and now I'm like sitting in support group meetings, other people dealing with grief, and they're talking about AMF and that for me was how I tried to deal with it.

• 15:55Dax Shepard?

  Yeah, yeah, yeah, yeah. It sounds a bit like you tried to treat it with action.

• 16:00Speaker 02

  Yes, exactly.

• 16:01Dax Shepard?

  As opposed to maybe perhaps sitting in discomfort.

• 16:05Speaker 02

  Absolutely. I was like, if you start feeling some discomfort, I'm like, I'm gonna go work on this non-pro.

• 16:08Dax Shepard?

  Yeah, yes. Okay, good. That was kind of my hunch. And then of course, that just waits there. At some point, it does start just kind of seeping out. How delayed was it for you? I lost my dad when he was 62 and I just had all these waves. First was just getting him through the whole thing. There's a lot of action there. Then there's action in the aftermath. And this is honestly years and continues to be waves of like, oh, right. Wow, I have a sadness now that I didn't allow myself to have then. And that's 13 years ago.

• 16:36Speaker 02

  Sorry that you lost your dad. I've had those waves and I think that you're right. If I sat with it more when I was 19, then I probably would have had maybe fewer waves.

• 16:44Dax Shepard?

  Also, who knows?

• 16:45Speaker 02

  Yeah, there's no way to know.

• 16:46Dax Shepard?

  I got in a drinking problem and you're fucking gone nowhere.

• 16:49Speaker 02

  Yeah, I will say that the one thing is that because my thing that I was channeling my time into was like, schoolwork and this grief support group, in that grief support group, I'm talking, I think I got maybe some of that out. But when I went on to get sick, that brought back a lot because all of a sudden I'm now laying in the hospital bed and my dad, my sister's around me and I was with them before. I was on that side.

• 17:10Dax Shepard?

  Yes, and you can't get into action because you are strapped to this thing. So let's get to there. So we leave Oxford, we go to Penn.

• 17:17Speaker 02

  That's right, for med school.

• 17:18Dax Shepard?

  And you're in your third year of med school? And what's the first symptom? You're like, everything's great, you're humming along, you're in your third college over many years.

• 17:27Speaker 02

  That's right. I was very healthy still. I actually won a bench pressing contest a couple of months before that.

• 17:33Dax Shepard?

  How much did you put up?

• 17:34Speaker 02

  I think it was like 325.

• 17:34Dax Shepard?

  Jesus Christ, wonderful.

• 17:36Speaker 02

  So very healthy. I am honored. OB GYN rotation, I'm now in the OB part of it. So I delivered my first couple of babies into the world, which in med school, that's this major highlight. As incredibly as I actually, I'll share a quick story about the second patient I delivered. The parents were both older than me, as you can imagine, because I'm 25. And they're sort of really concerned like, why is this like 25 year old in here?

• 17:56Dax Shepard?

  Not what I want. Not what I want.

• 17:59Speaker 02

  The husband comes to me, he's like, uh, this isn't your first time, right? I was like, whoa, no, because it was my second time. And I was like, uh, no, it's not my first time. I'm a med student, I'm just learning. And I remember like delivering the baby and baby's healthy and everything was all good. But then I remember turning around like, it was my second time. But like, your baby's really healthy and everything's all good.

• 18:19Dax Shepard?

  We got lucky. We all got lucky today.

• 18:21Speaker 02

  We're two for two.

• 18:22Dax Shepard?

  Oh my god.

• 18:23Speaker 02

  So yes, maybe I got sick as payback for that. But within the next couple of weeks, I started feeling more tired than I ever felt before. I'd been in school forever and I just never felt fatigue like that. And I started noticing lumps and bumps in my neck, which turned out to be in large lymph nodes and had abdominal pain. And then what was so weird, but I noticed like fluid pooling around my ankles. And I was like, but I'm like this like healthy 25 year old, what's going on?

• 18:44Dax Shepard?

  Also, can we add, and I love the irony of this. You're also a dude, you're in medical school and you probably ignored three or four red flags, right?

• 18:51Speaker 02

  Oh, for sure.

• 18:51Dax Shepard?

  Yes, isn't this insane? Like, you would think you'd be inoculated from this because you know about it, you're not.

• 18:56Speaker 02

  No, exactly. I'm literally feeling lumps in my neck. I'm like, oh, and I'm like, oh, these feel like lymph nodes, like that patient I felt on lymphoma two months ago. I'm like, that's weird, head on to something else. Like, I'm just, I'm just reading. Why am I not paying attention to any of this? Probably a lot of reasons for it. But so the fatigue got so bad, I would see a patient and then I would go find an empty room and I would take an eight minute nap. I'd set my alarm for nine minutes. I'd wake up eight minutes later, I'd go see another patient. I'd just keep doing that over and over again. Taking caffeine pills, 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.

• 19:34Dax Shepard?

  Really quick, from feeling the inflamed lymph nodes.

• 19:36Speaker 02

  Two weeks.

• 19:37Dax Shepard?

  Two weeks.

• 19:37Speaker 02

  Okay.

• 19:38Dax Shepard?

  Two weeks. So walking down the hall.

• 19:39Speaker 02

  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 sitting there, I'm like, why did I?

• 19:48Dax Shepard?

  Think that I'm about to die. What?

• 19:50Speaker 02

  And so like I finished the exam, I walked down the hall to the ER.

• 19:52Dax Shepard?

  Can we take one second right there? 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 this stuff I thought I cared about. It's a unique feeling, like for you to say you don't give a shit how you did on the test is really profound.

• 20:12Speaker 02

  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.

• 20:23Speaker 01

  But I don't know that you can get.

• 20:24Speaker 02

  But yeah, I used to have to be there.

• 20:25Speaker 01

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

• 20:29Dax Shepard?

  Maybe do a medically supervised overdose.

• 20:31Speaker 01

  Yeah, hopefully not. Hopefully don't have to experience it.

• 20:35Dax Shepard?

  I'm not going to a clinic that's like medically supervised.

• 20:38Speaker 01

  It is normally death related, though. It's moments where either someone around you is sick or has died, or you yourself are dealing with some health issue. So yeah, it does suck that you have to experience it like that.

• 20:50Dax Shepard?

  The main thing has to be in.

• 20:51Speaker 01

  So bad. Yeah.

• 20:53Dax Shepard?

  Yeah. Okay. So sorry. We go down the hallway.

• 20:55Speaker 02

  Yeah, I go down the hall. They do some blood work. I'm a med student, so I'm used to like being on the other side. It usually takes a while to come back and see the patient unless there's something really serious and then they come back really quickly.

• 21:04Dax Shepard?

  Yeah.

• 21:05Speaker 02

  The doctor comes back like 10 minutes later or maybe it was 15 minutes, but it was quick. He said, David, your liver, your kidneys and your bone marrow are shutting down. We have to hospitalized you right away. And I'm like, wait, what? I was just like, I delivered baby a couple of weeks ago. What do you mean? My organs are shutting down. They hospitalized me and then over the next couple of weeks, I go from my organs shutting down to being unconscious, gaining 100 pounds of fluid all over my body.

• 21:31Speaker 01

  Did you see the picture?

• 21:32Speaker 02

  100 pounds of fluid all over my body because my liver and my kidneys weren't working.

• 21:36Dax Shepard?

  So everything's just backing up.

• 21:37Speaker 02

  You're not urinating at all, so the fluid's just going everywhere. I had a retinal hemorrhage, which made me temporarily blind in my left eye, so I couldn't see anything out of my left eye.

• 21:44Dax Shepard?

  Couldn't have thrown any passes. Depth perception's gone.

• 21:48Speaker 02

  That's all I can think about, actually. I was like, darn it. This is gonna really hurt my

• 21:52Dax Shepard?

  You wouldn't go throw it 10 feet or 25 feet away?

• 21:54Speaker 02

  Exactly. And so I was getting so sick because of all the organs shutting down. I was on dialysis because kidneys weren't working. I was getting daily transfusions of red blood cells and platelets. They were just trying to keep me alive and no one knew what the diagnosis was.

• 22:07Dax Shepard?

  In that state, is your white blood cell count just like off the charts?

• 22:11Speaker 02

  So white blood cell count was pretty normal at that time. I don't have a good explanation for why. White blood cells were normal, but the platelets and the red blood cells were just collapsed. And you need platelets in order to prevent basically from you bleeding out at all times. Like, because you have these little microbleeds that happen all over your body, including your brain. And your platelets just sort of sop it up always. It's like fix a lot all over your body, all day, every day. And so when you get as low as mine, where you're in this critical state where you can have a little bleed in your brain and then you die from it.

• 22:35Dax Shepard?

  Let's take a second for your poor fucking father who loves his wife. And now he's visiting his

• 22:40Speaker 02

  Yeah. He spent every night in the hospital room by my side. So like, you know how they just like pull out couch things? This is horrifying. He spent every night with me. My sisters were amazing.

• 22:50Dax Shepard?

  Stay tuned for more Armchair Expert if you dare. We are supported by Alexa Plus. All right, let me tell you about something I'm genuinely excited to talk about. The all new Alexa Plus. Look, we're all juggling a million things these days and this thing is designed to actually make your life easier. It's like having a conversation with someone who really gets what you need. Picture this, you're planning a night out and instead of opening 12 different apps, you just have one conversation with Alexa and it handles everything. Dinner reservations, entertainment, the works. It learns your style and puts thousands of services at your fingertips. What I love about this concept is how natural it feels. You're not barking commands, you're just talking.

• 23:33Dax Shepard?

  And it works across your compatible devices, Echo, Fire TV and more. It's your all new, smart, proactive AI assistant. And honestly, the idea of having AI that actually anticipates what you need? That sounds pretty amazing to me. Check it out at amazon.com/newalexa.

• 23:51Dax Shepard?

  We get support from AG1. Fall is that time when your body and mind are getting ready for the winter. You're settling in, bracing for the cold. Your body's already running a deficit from the shorter days and broken sleep patterns. You don't want a nutrient deficit stacked on top of that, too.

• 24:07Speaker 01

  That's where your AG1 routine earns its spot. It's not fixing your sleep or your alarm time. It's giving your body what it needs so the dark mornings don't tank you before you even start. One scoop cold water every morning before anything else.

• 24:20Dax Shepard?

  AG1 Next Gen has 75 plus ingredients, vitamins, minerals, pre and probiotics, superfoods, backed by four separate gold standard clinical trials. Key nutrient levels improved with three months of consistent use.

• 24:34Speaker 01

  That's the part people miss. It's not a one day fix. It's what happens when you stay consistent.

• 24:38Dax Shepard?

  It's an easy, everyday thing. I've added it to my morning routine and I'm going to tell you, I actually love the taste of it. It's like Pavlovian. I drink it and I know, mm, I'm going to get that little vitamin buzz.

• 24:48Speaker 01

  Well, that's also the thing. When you do it first thing in the morning, you already feel kind of self-esteem because you're like, I already did something good for myself.

• 24:56Dax Shepard?

  Yes. Go to drinkag1.com/dax and for a limited time, get a free immunity bundle, including a bottle of omega three fish oil and a bottle of vitamin D3 K2 with your first subscription order of AG1 Next Gen or AG1 Pro. That's drinkag1.com/dax. And after checkout, be sure to let them know that armchair experts sent you. We get support from Scottsdale, Arizona. Monica, with summer ending or heading into fall, I've been researching a nice, quick getaway location and I keep coming back to Scottsdale, Arizona.

• 25:30Speaker 01

  Ooh, Scottsdale's good. What's drawing you to it?

• 25:33Dax Shepard?

  Well, first of all, I have this wonderful memory of going there as a kid when I would go see my stepdad when he was working out there. The weather is perfect in fall. Warm, sunny, no humidity. And you can really do whatever you want with your time there. I want to do a sunrise hike through the Sonoran Desert, be surrounded by Saguaro, and then at the same afternoon, just completely melt into a spa treatment at one of their luxury resorts.

• 25:58Speaker 01

  Oh, that sounds amazing. I want to. Do that. Also, I was there visiting my brother once and I loved Old Town Scottsdale. It's so walkable. They have galleries and cute little restaurants and shops. The food scene alone is worth the trip.

• 26:12Dax Shepard?

  What I keep reading is that it's luxurious, but not stuffy. There's no pressure to do it a certain way. You can explore public art, check out the architecture, go off roading in the desert, or just sit and watch a sunset.

• 26:24Speaker 01

  It really is the perfect fall reset.

• 26:26Dax Shepard?

  Learn more about all Scottsdale has to offer at unwindinscottsdale.com. We get support from ZipRecruiter. Oh, get recruiting. So I went down this rabbit hole the other day on real holiday jobs that exist and I couldn't stop. Somebody out there is hiring a ham glazer, a professional ham glazer. Another place is hiring a lead elf, implying a whole hierarchy of elves I had never even considered. Here's the thing, these jobs need real skills. People like that are hard to find. Whether you're hiring for one of these roles or any other role, the best way to find qualified people who are genuinely excited about your role is on ZipRecruiter. And right now you can try it for free at ziprecruiter.com/dax.

• 27:11Dax Shepard?

  Plus ZipRecruiter has a new feature that shows you the most interested qualified candidates first, so you meet the right people faster. No wonder ZipRecruiter is the number one rated hiring site based on G2. Let ZipRecruiter find the right people for your roles, seasonal or otherwise. Try it for free today at ziprecruiter.com/dax. That's ziprecruiter.com/dax. Meet your match on ZipRecruiter.

• 27:45Speaker 01

  Also, you told your mom you were gonna be okay. And then that was another promise. And then like,

• 27:50Speaker 02

  No, I thought about a lot, the promise I made to her because I was like, I promised her I was gonna help people. I was like, and I've just been like working, working, working to help people.

• 27:56Dax Shepard?

  Sucking up the system.

• 27:58Speaker 02

  I was thinking about that. Now you say it, I'm like, darn it. No, I was thinking, I'm not gonna help. I did all this training and now I'm not gonna help anyone. I told her I would. So with Francisco, he came in to see me. He like leaned in to give me a hug and he's a med student also. So he has a stethoscope around his neck. And I remember it was like slow motion because he comes and gives me a hug. And I see this stethoscope coming because any sort of trauma to my body could create one of these bleeds. And I see this stethoscope coming and it just like hits me like right between the eyes and we're just like looking at one another and for a split second we're like, oh my gosh, did he just kill me? They're like, my husband ran just like, he just like hit me in the head with this stethoscope. And then we like were sort of still for a second and then I didn't blackout because of an internal hemorrhage. And then we were okay and then we laughed about it, but it's crazy. That was what things were like back then when I was in the hospital.

• 28:38Dax Shepard?

  Yeah.

• 28:39Speaker 01

  Oh.

• 28:40Dax Shepard?

  Okay, so they end up giving you a crazy cocktail of chemotherapy.

• 28:44Speaker 02

  That's right.

• 28:44Dax Shepard?

  It was a last ditch effort.

• 28:47Speaker 01

  At this point, how long were you in the hospital?

• 28:49Speaker 02

  So I was in the hospital for seven weeks before they gave me this. First, they actually gave me high dose steroids because we didn't have a diagnosis. So first they give you a high dose steroids, things start to improve. And then four weeks later, it's roaring again. And this time is when I had my last rights read to me. This was now 11 weeks into my illness, right when we finally had the diagnosis. So diagnosed with Castleman disease, this rare disease where your immune system attacks your vital organs. Right around the time of the diagnosis, they give me first one chemotherapy. And thankfully that's enough to sort of hold things at bay. But then four weeks later, I'm back in ICU again. And that's when they give me seven chemotherapies.

• 29:24Dax Shepard?

  So yeah, your own immune system is killing you. And so they need to carpet bomb your immune system. So that's non-functional and that works.

• 29:33Speaker 02

  It does. The time they gave to me now, it's the third time that I'm on death's doorstep. And they tell me before, you know, we're out of options. So we're going to carpet bomb you with every chemotherapy we can think of at the highest dose possible. You know, I remember closing my eyes and being like, well, this is it. It's not going to happen. Hugged my family goodbye.

• 29:46Dax Shepard?

  Was there any peace at any point during this?

• 29:48Speaker 02

  You know, I have to admit during that six month period, there was never a moment. Oh, actually, no, there was one moment of peace, but for the most part it was this fight. Like, I can't believe this, like such sadness.

• 29:57Dax Shepard?

  With the diagnosis of Castleman, that doesn't get you shit, right? Because there's no real treatment for Castleman. Do they even know? I got quite curious whether we think this is a genetic condition or environmental. Do we have any sense of how Castleman comes about?

• 30:13Speaker 02

  Yeah, so my step type is called idiopathic, multicenter Castleman. Idiopathic means we don't know the cause. You don't ever want to have a disease that's called idiopathic. But we do know that even within idiopathic, that about 5% of patients will have a family member with Castleman's as well. And so. Those people, we feel pretty confident there's some sort of genetic heritability. But in the rest of us, we don't know what triggers this. I run a lab and our lab does spend time trying to figure this out. And we have found some what are called somatic mutations. So they're basically not mutations you're born with, but mutations you acquire over the course of your life. It's in the same way that cancer occurs because you acquire mutations in your life in those cells. We're observing somatic mutations in Castleman's patients.

• 30:50Dax Shepard?

  And where is that centered?

• 30:51Speaker 02

  Generally in the lymph node. And part of the reason that that makes sense is that the lymph node is sort of the home base for your immune system. So like if you're fighting an infection, you'll notice your lymph nodes get enlarged. And that's because your immune cells are fighting something and they go back to the lymph node and they talk to one or they communicate and they go back and they fight. They come back and they go out and fight. And so the lymph node is like the home base for your immune system. And so we think these are occurring in the lymph node. Therefore, all these immune cells are going out and wreaking havoc.

• 31:15Dax Shepard?

  So they're leaving mutated and so they're not good at reading its own DNA.

• 31:21Speaker 02

  The big thing is that in both of your immune systems, you want your immune system to be in surveillance mode, which means it's turned off, looking for bad things. And when it sees a bad thing, you want it to kill that bad thing. Then you want to turn itself back off and go back into surveillance mode. What we find in Castleman's is that our immune system turns on and then it doesn't turn off. And when your immune system's on and it's releasing all these bad things, it starts attacking healthy, good things like your heart, your lungs, your kidneys.

• 31:44Speaker 01

  That's autoimmune disorders in general, right?

• 31:46Speaker 02

  And autoimmune disorders typically are focused on one particular organ or one tissue type. So it might be the joints or it might be the heart.

• 31:53Dax Shepard?

  I have psoriatic arthritis.

• 31:55Speaker 02

  Yes, and so that's your skin and it's also your joints.

• 31:57Dax Shepard?

  Yes, yes, yes.

• 31:59Speaker 02

  Castleman's is like that, but it seems to be more nonspecific. It's not directed at the skin or the joints like in psoriatic arthritis, but it's more general.

• 32:06Dax Shepard?

  Okay, so this intense carpet bombing works, but it works for how long?

• 32:12Speaker 02

  For about a year. So now I'm out of the hospital for a year. I'm back in med school. And by the way, my girlfriend Caitlin and I were dating and somehow she like wants to stay with me during all this.

• 32:20Dax Shepard?

  You look rough. You did a 180.

• 32:22Speaker 02

  I did, I did.

• 32:23Dax Shepard?

  Yeah, yeah.

• 32:24Speaker 01

  Well, yeah, you had 100 pounds of fluid.

• 32:26Dax Shepard?

  And that kind of distended stomach you get when you have, I forget what condition that's called. But yeah, there's a lot happening.

• 32:31Speaker 02

  A lot's happening, yes.

• 32:33Dax Shepard?

  When do we put the MBA in the mix?

• 32:35Speaker 02

  So the MBA comes two years after I get sick with Castleman's because I spend the next two years, certainly battling my disease, but also when I have this relapse after I get the carpet bomb chemo, I decide I'm going to dedicate my life to trying to find a cure for Castleman's. But it took getting the carpet bombing and then I was actually put on an experimental drug that I would hope would keep me in remission. And it was. After it didn't work, that then I was like, I gotta dedicate my life to this. And then it was in the course of trying to figure out a cure for Castleman's that I realized that the barriers in the way of a cure for Castleman's were not science and technology. They were like, can you get people to work together? And can you collect enough blood samples for research? And can you come up with the right strategy? And can you raise money? And like, these are organizational business problems. And I was like, oh, the science is clear. The administrator stuff is going to prevent me from solving this disease.

• 33:20Speaker 02

  And actually, I mentioned that experimental drug is called soluximab. And it's hard for me to put into words what it meant when I got started on this drug, because Castleman's a rare disease. So there's 18,000 human diseases, and more than half of them are very rare. And it's like, you've probably never heard of literally 10,000 plus diseases ever. Castleman's is one of those, super rare. And it's very rare for them to have a clinical trial of a drug that might work. Like 95% don't have any treatments. Mine actually had a trial. And I was like, oh, my gosh, I know there's no solutions, but maybe this drug's gonna work. I was so hopeful. And I got put on it after the carpet bombing chemo. And I really believed and hoped that it would keep me in remission. And then a little bit over a year later is when I had that relapse. And it all came back. I'm back in ICU with all my organs shutting down.

• 34:00Speaker 02

  And that was so difficult emotionally to go from like, I think we got it. Like, this is the thing. Like, and I think it's gonna keep me in remission. And I actually met other patients who were in remission. I like saw them. They told me how they were in ICU for months. One person had part of his bowel resected. He had all these strokes. And he was walking around on this drug. And I was like, oh, my gosh, I can be like him. And then when it came back, it just wrecked me.

• 34:23Dax Shepard?

  True vulnerability hits when you relapse like that. And you had three relapses in five years?

• 34:28Speaker 02

  The total of four relapses of five episodes of this disease. And each one was so difficult for the emotional parts. I mean, obviously, there was the physical part. I'm in ICU. Because for each of them, I had gotten really hopeful. And I was like, we did it. And then it just all came back.

• 34:40Dax Shepard?

  Okay, so when do you get the kind of breakthrough thought that maybe I should approach this in an off-label way? And let's just talk about off-labeling in medicine and how that works.

• 34:51Speaker 02

  It was during that big relapse. And now this is flare number four, so the third relapse. And my doctors explained to me, okay, you've now failed to respond to the only drug in development. Like, soluximab is it. There's nothing else. It didn't work for you. He said, all of your organs are shutting down. I'm gonna try the same seven Chemotherapies again, there's just a few problems. One is that who knows if they're going to work again. You know, you've gotten them multiple times. They tend to lose their effectiveness as time goes on. Two, you're approaching the lifetime maximum of a drug called Adriamycin. There's only so much of these chemos that you can actually get before they cause cancer and organ dysfunction on their own. So you're approaching your lifetime max. So I don't know how many more times we can do this. And the third thing he said was, we've tried everything. There's nothing more we can do. And my sisters and my dad and my girlfriend Caitlin were sitting in the hospital room. And I remember we were just heartbroken because he's telling us.

• 35:35Dax Shepard?

  End of the road.

• 35:36Speaker 01

  Yeah.

• 35:36Speaker 02

  This is it, like this is it. And we're crying and it's horrible. And around maybe a minute or two of just like us all crying and bawling. I just remember thinking to myself, I'm like, wait a minute. You just gave me seven chemotherapies and none of them were made for Castleman's. They were all made for lymphoma and my Loma, and they worked. I know I keep relapsing, but how do we know there's not like an eighth drug out there? Did we try all the other drugs? There's 4,000 drugs.

• 35:58Dax Shepard?

  4,000 FDA approved prescriptions one could be given.

• 36:01Speaker 02

  Exactly. And so I've gotten 10 of them now between the different drugs. They've been like, there's nothing. Still like a lot left. And not to say every drug is possible, but how can you tell me that we've tried everything?

• 36:10Dax Shepard?

  We're at the end of the road.

• 36:11Speaker 02

  If I hadn't benefited from those seven, I wouldn't have thought that. They'd be like, oh, well, nothing else is going to work. I'm like, okay, they're probably right. Nothing else worked, but they gave me drugs that were working. So that became really clear. So I told my family, I was like, I'm gonna dedicate my life to trying to find a drug for this disease. They sort of were like, all right, Dave. Weren't particularly optimistic at that moment.

• 36:27Dax Shepard?

  As someone who loves someone going through that stuff, you're always really having a hard time debating whether or not you're gonna snuff out their hope or help them get to the part where we have closure. That's what you're trying to navigate. Like, no, my love, it's time for us to take stock of all the good stuff and have as much gratitude as we can have on the way out. It's hard.

• 36:45Speaker 02

  It's really hard because I also think back with my mom, probably two of the most important months of my life were the two months after the cancer was coming back, where we just were like present with one another. We were like looking at old home videos together.

• 36:57Dax Shepard?

  Not fighting.

• 36:58Speaker 02

  Exactly. And then I like, look at how I've handled this. I'm like, wait a minute, I didn't do that at all. We watched no home videos. I was like in the lab trying to figure out, is there a drug that could save me? And I'm like fighting, fighting, fighting, right? It really was, it was like, let's go. So yeah, it's hard to put those two things together.

• 37:12Dax Shepard?

  So once you have this idea, where do you start? 4,000 drugs, you start doing classes of drugs? How do you start weeding out?

• 37:19Speaker 02

  Great question. So the first thing I did was to try to start to understand what does the world know about this disease? And so there were 2,000 papers. I read those 2,000 papers to try to understand what do we know about Castleman disease? Second, I connected with all those doctors for all the papers that were written to try to start connecting them through an organization called the Castleman Disease Collaborative Network. So I created this nonprofit to basically let's centralize all the doctors, the patients, the loved ones. Let's get an understanding for what do we know? Cause I even heard there was a doctor in Japan that was trying this one drug. I'm like, well, I want to try that drug.

• 37:46Speaker 01

  How are you doing all this? Weren't you so tired? I mean, your organs are in flux. How are you doing this?

• 37:52Speaker 02

  I did none of this for the month that I was in ICU. So like I made the promise to my family and then I'm out for the next four weeks fighting for my life. But it's then, once I started to make it through that, that then it's like, all right, let's get to work. And so started reading papers, started reaching out to doctors. So coming up with sort of this network. And then the second thing was, let me look at all the related diseases. These that are kind of like Castleman's that are weird immune disorders, like psoriatic arthritis. What's out there? What are all these drugs that exist for other conditions?

• 38:16Dax Shepard?

  Cause we would agree, these labels are arbitrary.

• 38:18Speaker 02

  They are very arbitrary.

• 38:20Dax Shepard?

  There's a doctor dealing with six patients over here that calls it this thing. It could be the same thing, right?

• 38:23Speaker 02

  Exactly. And the drug companies, when they pick a disease to pursue, they've got a lot to pick from. Like they picked the IL-17 drug for psoriatic arthritis, but they could have picked a lung disease with the same drug. And they picked for a lot of reasons that had nothing to do with biology and nothing to do with whether it's going to work. It's like they have to figure out the most profitable opportunity.

• 38:39Dax Shepard?

  Yeah, kind of market.

• 38:40Speaker 02

  Just because it's not approved for it doesn't mean it's not going to work. So my mindset was, okay, let's figure out what we know about Castleman's. Let's start looking at related diseases that are like Castleman's. And then the last bucket, which was probably the scariest, or at least the most challenging was, I'm going to start collecting blood samples on myself and start trying to do research on my own samples. And the reason that was scary is because I didn't really know all that much about laboratory research. I found this amazing colleague at Penn who gave me some space in her lab, but I could do the first two. Like I could build a network and I built that organization, AMF. I could understand what other diseases there were, but like starting to do experiments, that was certainly the most challenging. And so, yeah, over the next year, built out the network and started identifying, you know, potential related drugs. Was storing my blood samples every couple of weeks in the lab.

• 39:21Dax Shepard?

  And so as opposed to you taking one of the medicines and Monitoring your symptoms, you were actually able to apply the medicine to your blood in some kind of a petri dish and observe it?

• 39:31Speaker 02

  So what I was doing was actually trying to understand in my blood samples, which of my immune cells were turned on, what were the proteins that were elevated in my blood versus healthy people and see if that could give me a fingerprint for what was wrong in my disease. My idea was that if I could figure out what was wrong, I could then see is there a drug that can reverse the thing that's wrong. Like if something's too high here, find a drug that can maybe make it go down.

• 39:53Dax Shepard?

  Yes.

• 39:53Speaker 02

  That was that third bucket in my mind that I wanted to do.

• 39:56Dax Shepard?

  How hard was just the figuring out which of these T cells or immune cells were the ones that were problematic? That feels hard enough right there.

• 40:04Speaker 02

  It is hard. Didn't even get to the third bucket before I then had my fifth relapse. I was just storing these samples. So by that stage, I started business school because I'd finished med school and I had this relapse and I had this long spreadsheet and I remember now I had a couple of drugs at the top that I thought maybe we should try because they were used in related diseases. I hadn't yet done the experiments in my own blood to figure out what could be maybe useful for me. And I remember I talked to my doctors about trying this one drug called psycosporin. We tried it. We were so hopeful and then it didn't work at all. My disease was just roaring through it. Organs were shutting down. All of the markers were bad. I was getting like worse and worse every day. And then I asked my doctors to try the number two drug on my list, this drug called IVIG. It requires an infusion. I remember I'm going to get that infusion and my doctor who I asked to do this, she asked me, she was like, do you want some fries for that order, David?

• 40:48Speaker 02

  Because I'm like asking for this IVIG.

• 40:50Dax Shepard?

  Yeah, well, that's, that was gonna be one of my questions, like, were you able to prescribe yourself this stuff? Cause you had your medical degree or were you reliant? And how hard is it to get other doctors to sign on to this approach?

• 41:01Speaker 02

  I was reliant on the other doctors and it's appropriately hard to get these medicines, right? Like it should be hard, you know, it shouldn't just be the drugs get thrown all over the place. But while it was appropriately hard and I needed to show them evidence and reasoning, I was dying. They'd already told me they tried everything. They already told me they didn't have anything else for me. So I'm telling them things that maybe we could try.

• 41:19Speaker 01

  You're like, I'm here to be a lab rat now.

• 41:21Speaker 02

  Exactly. And I was willing to take on all the risks. It's like, I know that the drug could kill me, but I'm not going to live much longer. And so the IVIG, they gave me the infusion, everything stopped. All the things that were getting worse halted.

• 41:33Dax Shepard?

  In like what timeframe?

• 41:34Speaker 02

  Within a couple of days. So like it's halting and I'm with Caitlin and we're engaged and we're like.

• 41:38Dax Shepard?

  Are you scared to trust it as well, though?

• 41:40Speaker 01

  Yeah.

• 41:41Speaker 02

  I sort of wish I was.

• 41:44Speaker 01

  You're just so humble, so nice.

• 41:47Speaker 02

  I was like, IVIG. I remember literally saying the words, we did it, Caitlin. We did it. And so a couple more days go by and then all of a sudden, things start getting worse.

• 41:55Speaker 01

  No.

• 41:58Speaker 02

  I'm like, this can't be. We go for blood work. It's getting horrible. Within a couple of weeks, now I'm back in ICU with everything shutting down. And I just tried the two things that were like the top of our list. I gave it my best. I wasn't ready to like fully accept it, but at least we tried it. And I had the feeling like we tried and we failed. And then my doctors gave me the same seven chemotherapies. This time they gave me the highest dose they'd ever given a human of this one drug called atobasid. And I remember saying goodbye to my family again and saying goodbye to Caitlin. I was just heartbroken about it. And Caitlin and I were supposed to get married five months later and I felt like I failed her.

• 42:31Dax Shepard?

  She wasted all this time.

• 42:33Speaker 02

  Yeah, she'd been with me for all this time and she is just amazing. I remember sort of starting to close my eyes and let go. I remember falling asleep and realizing that this was it. And a couple of days passed and that crazy intense chemo worked just enough. Like I squeaked by. I remember starting to wake up and just being shocked. It was a lot of feelings. Like one was shock, another was, oh my gosh, this is so exciting. Like I'm.

• 42:59Speaker 01

  The amount of times you've said it worked.

• 43:02Speaker 02

  But this time I didn't say it worked. It was like, because of what happened just a couple of weeks before. But then it was immediately the sense of urgency was like, okay, I've got a window. I don't know how long it's gonna be. I turned, my sister Gina was on my left side and Caitlin was on my right side. And I remember turning to Gina and I was like, hey, G. And they're both like, oh my God, damn. Hey, G, can you go downstairs and see if you can get that lymph node they just cut out and send it to Philadelphia? And I was like, and Caitlin, will you call UNC and send those blood samples to Philly? Can you get the records to go down too? And they're both like, what? And I was like, because I'm getting out of here. I was like, and we gotta find a drug for this thing. And so it was about three weeks of me recovering, just like, I gotta get to Philly, I gotta get to Philly, I gotta get to Philly. So I got to Philly and I thought of the blood samples and started doing experiments. This is when I was now in that third bucket, which is what are those immune cells doing? What proteins are too high?

• 43:47Speaker 02

  I spent about three weeks doing experiments. And by the end of it, I was pretty convinced that this one part of my immune system called mTOR. So your immune cells, they're all over your body, literally billions of cells. They have to communicate with one another and be able to let cells in different parts know what's going on. One of the key communication lines in your immune system is called mTOR. The research I had done on my own samples suggested it was turned into overdrive. There's like too much mTOR on. You can imagine like if your fire alarm is mTOR and it's saying like, there's a fire here and it's stuck in overdrive. Your immune system is going to go berserk. In my opinion, and the data suggested it's a false alarm. Like the alarm is going off, it's going berserk, but there's nothing to fight. So when I saw this result, I got so excited because there are drugs that are called mTOR inhibitors. They've been around for decades. They actually were made for organ transplant rejection.

• 44:29Speaker 02

  Because if you get a kidney, your immune system will attack that organ and it'll turn mTOR on. But if you turn mTOR off, the alarm goes off and you don't attack that kidney. So I was like, oh my gosh, we can try an mTOR inhibitor. And so I took the data to my doctors and they prescribed me this mTOR inhibitor called serilimus.

• 44:45Dax Shepard?

  It was like a 10 year old drug at the time?

• 44:47Speaker 02

  Been on the market 15 years, sort of known for a few decades. And yeah, now it's been over 11 and a half years that I've been doing great on this medicine.

• 44:53Speaker 01

  Wow.

• 44:55Speaker 02

  No relapses, full health. Yes, let's start knocking it all away.

• 44:59Dax Shepard?

  The question I don't want to ask, but I got to ask is how many of these drugs your body kind of adapts?

• 45:04Speaker 02

  How long is it going to work for? Yeah, it's the right question. I mean, I think that what's so crazy is how long it's been.

• 45:09Dax Shepard?

  Well, to me, you know, Evan's like, you've definitely passed that window where stuff stops.

• 45:13Speaker 02

  But you can imagine that every day that went by afterwards, I used to measure, someone would be like, how long have you been in remission for? And I'd be like 37.29 months. And they're like, what?

• 45:23Dax Shepard?

  You're like someone in sobriety.

• 45:24Speaker 02

  Yeah, I'm like, I can't round up. You don't know what's going to happen tomorrow when you're going through these sorts of things. But I know it's been like 28.29. And so the months added up, I made it to Caitlin's wedding day, May 24, 2014. My hair grew back just in time for the wedding.

• 45:36Dax Shepard?

  Nice.

• 45:37Speaker 02

  It looked like a buzz cut.

• 45:38Dax Shepard?

  That was a great do, but.

• 45:39Speaker 02

  Back in time. And yeah, the months have just sort of stacked and stacked.

• 45:42Dax Shepard?

  Okay, so you come out of this and I don't know in order, but you get a job as a professor at Penn in the medical school.

• 45:49Speaker 02

  That's right.

• 45:49Dax Shepard?

  And you have a lab.

• 45:50Speaker 02

  Yep.

• 45:51Dax Shepard?

  And you decide to really dedicate yourself to exploring. These other 18,000 diseases with these 4,000 medicines that exist to see what off-label stuff could exist. Are you immediately employing AI? When does AI enter the picture? Because it's gotta be almost impossible without AI.

• 46:09Speaker 02

  Yes, that's right. So the moment that Syrilime started helping me, I just remember having these flashbacks to walking past the CVS and being like, wait a minute, it was in there. All those three years that I was dying from this thing and all those five times I said goodbye to my family, like, it was in that CVS. And I just never knew it. Like, no one knew it.

• 46:29Dax Shepard?

  Stay tuned for more Armchair Expert, if you dare.

• 46:36Dax Shepard?

  We get support from Superhuman. Look, I love what I do. The conversations, the ideas, the creative stuff. But there's this whole other layer of work that eats my day alive. The inbox that never ends. Docs I need to get through, threads I'm behind on. And by the time I've dealt with all that, the stuff I actually want to focus on gets whatever's left. What I needed was something that just works where I'm already working. Not another tab to open, not another thing to set up. Superhuman Go, from the makers of Grammarly, is different. It's already right there. Inside your email, your docs, your browser. You don't go to it. It's already working alongside you. You're deep in a long thread, highlight it, and it pulls the key points. About to send something important?

• 47:18Dax Shepard?

  It flags what doesn't add up before it leaves your hands. It knows your style, your workflows, and it just backs you up without getting in the way. A thought partner that's already up to speed. At your service, not after your job. So, do yourself a favor and try Superhuman Go, from the makers of Grammarly. Find out more at superhuman.com. We get support from Instagram teen accounts. So, we talk a lot on this show about how the world is different now than when we were growing up. And one of the biggest differences is obviously social media. And I think a lot of people wonder, okay, what's actually being done to make it safer for teenagers?

• 47:56Speaker 01

  Which is a fair ques-

• 47:57Dax Shepard?

  Yeah, so Instagram has got something called teen accounts and they come with automatic protections built in by default. So anyone between 13 and 17 is automatically placed into this experience. They get age appropriate content settings, contact limits, so that by default, only people they're already connected to can message them. And time management tools, daily time limit reminders, and also sleep mode that mutes notifications from 10pm to 7am.

• 48:23Speaker 01

  Sleep mode is genius.

• 48:25Dax Shepard?

  Right? And here's the thing, for anyone under 16, a parent has to give permission to change any of those settings to be less strict. The guardrails are on and Instagram keeps building new safety features to create age appropriate experiences for teens.

• 48:40Speaker 01

  I am really glad Instagram is helping to give parents peace of mind with teen accounts.

• 48:44Dax Shepard?

  Learn more about teen accounts and Instagram's ongoing work to protect teens online at instagram.com/teenaccounts. We get support by Peloton. You know that feeling when you're spiraling over a problem and you just can't figure it out? When that happens to me, I need a change of pace and I've found that running is the best way. It takes my brain out of the driver's seat and I come back with a fresh perspective. Running can be freeing and cathartic and Peloton helps you feel all of that. And now that feeling fits wherever you need it with the new Peloton Tread Flex. It's movable and foldable, designed to fit your life. So next time you feel stuck, you can go for a run literally anywhere, whether that's in your

• 49:27Dax Shepard?

  office, living room, or even the attic. Plus, they have classes with expert instructors and programs to meet you at any level and keep you moving. Let yourself run. Explore the new Peloton Tread Flex at onepeloton.com.

• 49:42Speaker 03

  If you like YouTube, you'll love YouTube Premium. It's destroying athlete, creator, and YouTube Maxer. YouTube Premium enhances how I use YouTube with awesome features like offline downloads, so I can download my favorite training videos before I hit the gym. So no wifi doesn't turn leg day into loading day. Plus, I get ad-free videos, background play, and so much more. YouTube Premium is like YouTube got some extra gains. Try YouTube Premium for two months free at youtube.com/premium.

• 50:12Speaker 04

  Hey, what's up, guys? It's Haley Bailey. Okay, I need to tell you about something. I just got YouTube Premium. It's got tons of awesome features like offline downloads, so I can download my favorite videos before I travel and watch them whenever I don't have Wi-Fi. Because we all know airplane Wi-Fi is the worst. I get ad-free, I get background play, and there's like a ton more in there. You should try it. If you like YouTube, you'll love YouTube Premium. So try YouTube Premium for two months free at youtube.com/premium. Trial eligibility varies. Terms apply. Cancel anytime. That's a mouthful.

• 50:48Speaker 01

  Are you kind of like, why didn't all these doctors figure? I'd be mad.

• 50:52Dax Shepard?

  You would.

• 50:52Speaker 01

  Well, I'm just in here doing my own blood and testing. Why aren't these other doctors doing that?

• 50:58Dax Shepard?

  I think you have to acknowledge how myopic the field of medicine is. You are an oncologist. His father's a surgeon. You're not in the synthesizing generalist business. You're in the specializing business. And generalizing and synthesizing is so hard. This is why people were freaked out, you know, that Homeland Security was tapping everyone's phones. And so it's like, this is a fucking joke. Nothing can synthesize all this information. You can gather information all you want, but to actually find patterns within information is so time-consuming and nearly impossible for a human to do.

• 51:30Speaker 02

  I completely agree. And then also, the incentives are the other problem for why this doesn't happen.

• 51:34Dax Shepard?

  Yeah, you're not going to launch a new drug. Hopefully, you're going to pick up another few patients, but it's going to be a few. So the pharma company is not incentivized to figure this out.

• 51:42Speaker 02

  That's exactly right. So once I started, oh, my gosh, how many drugs are out there? It's like, okay, this worked for me. Are there other drugs out there for other people? And I'm just thinking about like the patients that I took care of in med school, where we said, this is it, we're out of options. Like, well, maybe we weren't. Maybe there was something else. I think about my mom. Maybe there was something that could have helped her.

• 51:57Dax Shepard?

  I'm going to add too, it's not a sexy idea.

• 51:59Speaker 02

  No, not at all. It's like recycling old drugs.

• 52:01Dax Shepard?

  We like inventions and breakthroughs. And we don't like hearing the fucking answer was sitting next to us the whole time.

• 52:06Speaker 01

  Well, unless you have the ailment, then it's really sexy. Like, it's already here.

• 52:11Dax Shepard?

  Yeah, yeah, of course. It's just our nature is to want the breakthrough and the next thing and the next clinical trial and not, hey, we already had it.

• 52:18Speaker 02

  That's exactly right. The people who are doing the work are not. Not incentivized is the patients like we are incentivized to do. We can benefit from it, but the people actually doing the work are not going to benefit from it. The same way that they would a new drug. So decide that, okay, this is what I want to do with my life. I want to find new uses for the medicines we have. I want to save people with treatments that already exist, just in the same way that I was able to be saved. And so joined the faculty at Penn. And of course, we started focusing on Castleman's and other related rare inflammatory diseases. Rare cancers, rare autoimmune conditions.

• 52:45Dax Shepard?

  Cause there's some weird overlap.

• 52:47Speaker 02

  That's exactly right. So Castleman's is very similar to multiple myeloma, it's similar to Poem Syndrome. There are these weird inflammatory conditions and cancers that overlap. And so start studying them and we start finding more repurposed drugs. I'm like, wait a minute, there's more for Castleman's and there's more for Poem Syndrome.

• 53:02Dax Shepard?

  Sadly, you had recommended to another guy suffering from Castleman's to take what just worked for you. And you were so excited to share it with them. And then it worked for a minute, but it didn't work.

• 53:10Speaker 02

  It worked in some Castleman's patients, not in others. I remember the first Castleman's patient that I got to see, because we treated patients in various parts of the world, but that I actually got to see in person, a young boy named Joey, who responded incredibly well to it. So of course, Monica, you're going to laugh with me that here I am again, like we figured it out. Like Castleman's is taken care of. Look at Joey, like it's working for everyone. We're done with Castleman's.

• 53:29Dax Shepard?

  I was directing the sitcom version of this, like he would always pop champagne. And just like by the 20th time we saw him pop champagne, we were laughing so hard.

• 53:35Speaker 02

  I know.

• 53:36Dax Shepard?

  But you need that spirit, actually.

• 53:38Speaker 01

  It takes that.

• 53:39Dax Shepard?

  It's essential.

• 53:40Speaker 01

  Type of mentality.

• 53:40Dax Shepard?

  That's right.

• 53:41Speaker 01

  Thank God.

• 53:41Speaker 02

  So we start helping these other people and then it's other diseases. And so angiosarcoma, this horrible cancer, we find that there was research that was done three years earlier about a potential drug that could be useful for it, but it was done in the lab and it was never given to a patient. And we treat a patient with it and it works for him. And like he has this uniformly fatal cancer. And actually this person is actually my uncle. And so that's even why I was thinking about it. My uncle, Michael, he got this horrible diagnosis. Everyone dies within a year.

• 54:07Dax Shepard?

  I hate to be, this is too much stuff in your family. You guys all on a well. Like some point I get suspicious of your environment. This is like a definitely disproportionate amount.

• 54:18Speaker 02

  We've had a lot of suffering.

• 54:19Dax Shepard?

  Yes.

• 54:20Speaker 02

  So figure out the basically this work had been done three years earlier, but no one ever tried it in a patient. So we get Michael on this drug. It works incredibly well. Last month, he walked his daughter down the aisle on her wedding nine years later. This is crazy, incredible. So start giving it to other patients. It turns out it works in about 18% of patients. So it's not everyone, but 18% of it works in, it's everything. You're living years instead of weeks. And so that for me was this major eye opener. The other drugs we discovered, the repurposed drugs, we did a lot of hard lab work to figure it out, doing experiments in my blood and other people's samples. But we didn't have to do anything for Michael. We said to find a paper that someone else had published and everyone had just disregarded because like you can't read millions of papers a year and stay on top of everything. And so here I was like, wait a minute, maybe there's actually breadcrumbs that are already out there.

• 55:03Speaker 02

  So we don't even have to do all the crazy hard lab work. And so that was a really important moment for me. And fast forward over these 11 years, we've now advanced 14 repurposed drugs for a number of rare diseases. We save thousands of lives, including angiosarcoma patients. But about three years ago was when artificial intelligence was really coming on the scene. And to your point, we could do 14 drugs for rare diseases, saving a few thousand lives. But AI actually would allow us to say like, instead of looking at these few diseases, we actually can look at all 4,000 drugs and all 18,000 diseases and let AI actually score globally. Every drug, every disease in a way that one lab never could, one person never could. And so that was the big unlock.

• 55:43Dax Shepard?

  The whole school, if you dedicated the school, no, couldn't do that.

• 55:46Speaker 02

  Years, it would be impossible for humans to do. So three years ago, my best friend from medical school, Grant and I and Tracy Secor, we co-founded Every Cure, this nonprofit, with the idea being that we want a nonprofit that's on a mission to save lives with the drugs we already have. It's here to unlock the potential of the treatments we have to treat the diseases that ail us. And we use AI to actually quantify every drug to treat every disease. So there's 4,000 drugs, 18,000 diseases, that's 75 million possibilities. If you tried every drug and every disease, you do it 75 million times, we get a score from zero to one for every one of them, for how likely it is to work.

• 56:16Dax Shepard?

  Yeah. So what's the max out of that zero to one range? I read that and I was just curious, what do you see normally or what's outrageous? Like a point seven is like, whoa, we got something.

• 56:26Speaker 02

  It's a good question. It's a fairly linear scoring system. So there's actually a lot of point nine, nine, nine, nine. The idea being that we want to look at the point nine nines. The whole point of the score is to always say like, what are the things at the top? Cause if you start with Castleman's only, it's like, well, you might find the best drug for Castleman's. But is that the best drug for humanity to use? Is that the best match between a drug and a disease? Probably not. But if you do this all versus all, to your point, like you can look at the things that are the point nine nines. And you come across things where like, really? But then you dig into it deeper and you figure out.

• 56:53Dax Shepard?

  Vitamin that you've discovered had an impact on nonverbal autistic kids. This seems impossible.

• 57:00Speaker 02

  Yeah, 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. 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.

• 57:35Dax Shepard?

  Can leapfrog this whole.

• 57:36Speaker 02

  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.

• 57:48Dax Shepard?

  Let me ask you really quick, 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?

• 58:03Speaker 02

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

• 58:20Speaker 01

  Is it just a pill?

• 58:21Speaker 02

  It's just a pill.

• 58:22Dax Shepard?

  Yeah, give the example. One kid was nonverbal for five years.

• 58:25Speaker 02

  That's Ryan. Ryan was basically nonverbal for five years. He could do something called echolocia, 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 the 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. Within two weeks, starting lukavoran, he told his dad for the first time ever a statement. And he said, Daddy, I love you.

• 58:47Speaker 01

  Oh, you can't even write.

• 58:49Dax Shepard?

  That would have killed dad on the spot.

• 58:51Speaker 02

  Like I cried for the next 15 minutes.

• 58:52Speaker 01

  Oh.

• 58:53Speaker 02

  I couldn't do anything.

• 58:54Speaker 01

  Can you imagine?

• 58:54Speaker 02

  He couldn't even leave the house.

• 58:55Dax Shepard?

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

• 58:58Speaker 01

  Oh, because he's been stuck wanting to say this.

• 59:02Dax Shepard?

  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.

• 59:10Speaker 02

  Could you imagine?

• 59:11Dax Shepard?

  But there's been multiple success stories.

• 59:14Speaker 02

  There have. Multiple success stories. Next, 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 do is ask me for more. And I was like, that's exactly what my kids are, more, more, more, more, more.

• 59:28Speaker 01

  That's very human.

• 59:29Speaker 02

  Me too.

• 59:31Speaker 01

  Oh, my gosh, that's so incredible.

• 59:33Speaker 02

  Yeah, and so like, this is why we wanted to start every cure, because there's things that are out there. And I love that every cure in 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.

• 59:47Dax Shepard?

  Yeah, I want to hear those two things. I want some more examples. And I also want to know, I keep reading, you guys trained this model to do this.

• 59:55Speaker 02

  Yeah.

• 59:55Dax Shepard?

  But how the fuck do you take this tool we have and actually get it to go through every single medical journal ever written? How do you construct that? That's its own breakthrough.

• 1:00:05Speaker 02

  It is. So we utilize something called biomedical knowledge graph. So a knowledge graph is a way to basically construct and bring together lots and lots of information from disparate places. So imagine a knowledge graph would be if we had on the wall, every drug, every disease, every gene, everything we know about medicine, all as one node each. And then you've got lines connecting all of them based on the relationship between them. So we use every paper that's ever been written, all data we can find online, anything that we can find, we'll fill out this graph. So every concept plus all the relationships between them. So it's like, so tuxomab treats Castleman disease, IL-6 elevated in Castleman's. But imagine that for everything on this graph.

• 1:00:38Dax Shepard?

  Yeah.

• 1:00:39Speaker 02

  So now this search is the perfect ingredients to then train machine learning algorithms. Because we can say, you know, this whole graph here, this drug works for this disease. This drug works for that disease. And we train it on the known treatments. And what it'll learn is that there was a paper that was published three years earlier, like an angiosarcoma, showing that this drug might work in that disease, and it did. And so understand these patterns. And then we ask the exact same algorithm now that we've shown that this drug works for this disease. Now give us a score from zero to one for how likely every other drug is to treat every other disease based on these pattern of connections.

• 1:01:07Dax Shepard?

  And do we owe the Scandinavians the biggest debt of gratitude? I don't think the ones that have kept the best medical data and made it. It's not public, but it's public. It's obscured, but it's all there.

• 1:01:17Speaker 02

  Yes, Northern Europeans have done a great job with electronic medical record data.

• 1:01:21Dax Shepard?

  These like epidemiological studies in five seconds.

• 1:01:23Speaker 02

  Absolutely, yes. Everyone's in the same database, which a lot of other countries, we don't have that.

• 1:01:27Dax Shepard?

  I know we all have privacy concerns, but there's got to be a way. Everything I've gone through with this whole psoriatic arthritis thing, like I could save someone years if you could access my thing and just not know my name.

• 1:01:37Speaker 02

  I feel like we need to move towards that. Yeah, why is this not happening on its own? Like, what's broken about our system? And I think there's a couple of things that have just completely shocked me. So first of all, those 4,000 drugs we have, 80% of them are generic, which means that once a drug becomes generic, anyone can make a copy of that drug, the exact same drug, it's the same name. And when you have 10 people making the exact same drug, the price plummets, which is good for our healthcare system. It's not a cheap drug, but now it's like a penny a pill of profit per sale. And there's 10 different companies all selling what one company used to sell. So you might find that that drug could work for a million people with another disease, and no one will make any money off of that. The depressing thing is that that shouldn't matter, but it does matter. It's not that people are hiding, it's just that if you can't make any money off this

• 1:02:19Speaker 02

  thing, you can't spend millions of dollars doing clinical trials and then actually raising awareness about it. Somehow 80% of the drugs we have, there's no incentive to find a new use for them at all, even though they're there and they're safe and we know how they work and we know everything about them. And they're the things that are perfect for a knowledge graph because we've got a lot of knowledge about them. Of course, everyone's using AI to find new uses for medicines, but no one's using AI to find new uses for old medicines. Right. And so that financial problem is huge.

• 1:02:44Dax Shepard?

  So real before you move on to the next one, what's the solution for that one?

• 1:02:48Speaker 02

  We feel that the solution is to create a nonprofit that doesn't have to be driven by profit. So we've got this financial problem, which is that it's not profitable to find a new use for an old medicine. And then on top of that, we have an issue that somehow no entity is taking responsibility to be like, I know that there's this market problem over here, but we're the NIH or the FDA or we're some entity, we're just going to do this. Like, we're just going to find new uses for medicines. And so there's just been this huge gap. And then to your point earlier, there's also never really been the technological capability to really do this at scale. So maybe we can't blame the system too much because it's only recent that the system could even address this.

• 1:03:22Dax Shepard?

  Yes.

• 1:03:22Speaker 02

  But when you bring those three things together, we have this horrible situation where there's all these drugs that could help people, all these people that are suffering, and no one doing the work to bring them together.

• 1:03:30Dax Shepard?

  But you're here now.

• 1:03:31Speaker 01

  Thank God.

• 1:03:31Speaker 02

  Yeah, it's all every year.

• 1:03:32Dax Shepard?

  Okay, so give us a couple more. I read an article maybe in The New Yorker about Joseph Coats.

• 1:03:37Speaker 02

  Joseph was diagnosed with a rare cancer called Poem Syndrome. He actually was initially thought to have Castleman's disease. And so that's how we initially got connected. He came to a conference and I got a chance to meet him. His diagnosis was changed correctly to Poems. And a few months went by and I hadn't heard anything about how Joseph is doing or what was going on. And then his girlfriend Tara reached out. She said, David, since I saw you guys last, Joseph got really, really bad. He's in ICU right now and he's on life support. This was a Friday and by Monday, the doctors are going to take him off of life support and put him in end of life hospice care. And I remember just being so shocked, like, oh, my gosh, I saw him just a few months ago. He has so much life and energy and love and just heartbroken for it. And Poem Syndrome is a condition that I mentioned is in the sort of same

• 1:04:21Speaker 02

  family as Castleman's and myeloma. So I knew enough about it to where I felt comfortable really digging into see like, are there drugs we could recommend for Joseph? I know that his doctors are ready to give up, but can we just try something? And so I was able to get in touch with his doctor on that Saturday. And his doctor graciously called me back on a Saturday. I recommended three drugs that are typically used for multiple myeloma, which again is a similar cancer to Poem Syndrome. That doctor hadn't considered. In hindsight, it's like, let's be creative here. Yes, there's nothing for poems, but like, let's look to the side of poems.

• 1:04:49Dax Shepard?

  Yeah.

• 1:04:49Speaker 02

  Thankfully, he listened to me and he's like, well, I'll talk to the family and I'll talk to my colleagues. Maybe we'll try them. But he was actually very worried about the fact that the chemotherapy that we were recommending was going to kill Joseph. And I talked to him and said, but you're going to take him off life support on Monday. He's going to die from his disease. Let's give him a shot. Let's try this.

• 1:05:07Dax Shepard?

  Yeah.

• 1:05:07Speaker 02

  He made the decision to try these three drugs. And we just sort of waited for the next few days, like, what are we going to find out? And then within a few days, heard that things started to improve. And I can't tell you.

• 1:05:17Dax Shepard?

  You got that bottle of champagne out.

• 1:05:19Speaker 01

  Oh, no.

• 1:05:20Speaker 02

  Exactly.

• 1:05:22Dax Shepard?

  Cuts a cigar tip.

• 1:05:24Speaker 02

  He responded, he got out of the hospital. And then what's so amazing is that Poem Syndrome is a condition where if you can get into remission, like we got him into, we did a stem cell transplant for him. And so he's potentially even cured right now. So like, I saw him just a few weeks ago and he's got the most incredible energy and he's so positive. And he's got his life back. So I should also mention, this is an example. And at every cure, the way that we work is so we scan every drug against every disease or AI platform. Our med team finds the best matches and then we move them forward. We do lab studies, we do clinical trials. With this whole systematic approach to fix this system problem. And then also in parallel, we get contacted by patients like Joseph and Tara. I struggle so much because I want to help them. I want to throw the Hail Mary in the same way that we did a Hail Mary for me.

• 1:06:07Dax Shepard?

  Yeah.

• 1:06:07Speaker 02

  And at the same time, we have this systematic process where we've got a 50 member team where we're using AI. We have to focus on that. Like we've got this responsibility from a systems level because there's people at the other end of these drugs that we're working on that are waiting for solutions. But then there's also people who are reaching out to us like Tara and Joseph. And that's probably the biggest struggle that I have is how do I balance the two? Because we've got an amazing team, but our team can't actually pursue every disease that we're contacting.

• 1:06:31Dax Shepard?

  I hate to be crude, but you could be penny wise and pound foolish.

• 1:06:34Speaker 02

  I think that's the right analogy here. And so what we have to do is we have to say, okay, if you match every drug to every disease, what are the best opportunities? We have nine programs already. We launched this nonprofit three years ago. We built our platform over the first couple of years. We've only been using the pipeline for 12 months. We already have nine drug disease matches that we're advancing forward from breast cancer.

• 1:06:53Dax Shepard?

  And there's this lidocaine thing, which is bizarre. Tell Monica about this.

• 1:06:57Speaker 02

  Yeah. So amazingly, there's really interesting both laboratory and clinical data on the potential role that lidocaine injection could play in individuals with breast cancer. So lidocaine is the numbing medicine you get when you go to the dentist, right? So injecting it around a breast cancer tumor before surgery, there was a large trial that was done in India of 1,600 patients. And those patients who had it injected around their tumor before surgery had a 29% reduction in mortality at five years versus people who didn't. But lidocaine, like this simple substance, and it was published in a major journal called the Journal of Clinical Oncology, one of the best cancer journals in the world. We're looking at it in our platform. It comes through our pipeline and we're like, people must be using this, right? It's like super cheap and it's widely available. But then we learned that no one is using this. The paper's out there, the study's done, and the general consensus from a lot of folks is like, well, you guys should do another study,

• 1:07:42Speaker 02

  another seven year study and see how people are doing. The question is, do we need to do another seven year study? This one's already proven. A randomized controlled trial. It's already going to be used in. Surgery and so we are doing more lab work now because the other thing that doctors like is to understand why something might work because like oh we injected lidocaine and people died less like well why so we are doing lab work to try to figure out the mechanism we've got some hypotheses one is there's a lot of evidence to suggest that during the actual act of surgery to cut out a tumor whether it's breast cancer or you name the tumor that that's apparently a moment when a number of cancer cells become very migratory they basically try to escape from the region it's partly because there's decreased blood flow because there's trauma that's occurring in the area so the thought is that there's actually metastases that occur while you're operating it's actually migration and of course this is a hypothesis but it's something we're

• 1:08:25Speaker 02

  studying so the idea for how lidocaine may work is that lidocaine is very good at making cells non-migratory it stops it from moving the thought is that maybe we prevent what would have been a future metastasis to your liver or you name it from being able to get out of the space before the surgery happens

• 1:08:42Dax Shepard?

  You're like kind of paralyzing

• 1:08:43Speaker 02

  Paralyze it and you actually do the injection eight to 10 minutes before surgery so you're like paralyzing it then you cut it out and at least in these patients in India it was a game changer

• 1:08:51Dax Shepard?

  We trust India

• 1:08:52Speaker 01

  Yeah, we like that

• 1:08:53Speaker 02

  So these are the kinds of things that we would have never thought to look for

• 1:08:56Dax Shepard?

  One that blew my mind is botox in the frowning because that is a cycle as we know the people that were famously documenting all the face shapes were giving themselves emotions and this is a two-way street and just numbing the ability to frown can have an impact on depression maybe crazy

• 1:09:13Speaker 02

  Yes, so this idea with botox is there's actually have been clinical studies that for about three or four months after a botox injection right here between your eyebrows there's improvement in moods

• 1:09:22Speaker 01

  So it's crazy

• 1:09:25Speaker 02

  Right and so we got to figure this stuff out and I mean we actually just talked through two of our nine programs but one of my favorite ones is this rare condition called Bachmann buff so kids are born on feeding tubes they're unable to move it's a horrible condition it's because they have too high levels of an enzyme called OCE1 and so what's so interesting is that African sleeping sickness is a condition that involves elevated levels of OCE1 so there's a drug called DFMO that blocks OCE1 for African sleeping sickness well it turns out that OCE1 is also too high in these poor kids that are bed bound on feeding tubes if you give that drug DFMO to these kids and there's now been about 10 kids treated the early The more likely they might have their feeding tube taken out. They might sit up. They can even walk. I keep saying this is why we started EveryCure. Every one of these is why we started EveryCure. But this is it, right?

• 1:10:10Speaker 02

  It's like this super rare disease. This super cheap drug's been around for decades. No one's ever gonna do the work to get it to every patient possible. But we at EveryCure, we can do that. We can get involved in trying to diagnose more kids, to make sure that more kids get DFMO. This is for us why we did this.

• 1:10:23Dax Shepard?

  Well, okay, so if people want to support EveryCure, what should they do?

• 1:10:26Speaker 02

  Go to everycure.org/donate to donate to us. Also, a big part of this is awareness raising. So thinking about some of the drugs we've talked about and even others that we're working on. Part of it is doing really good science, great lab work, great clinical trials. But another part is actually just getting the word out. If you know someone who might be able to have this blood test, it might be helpful for someone in their family. So go into our website, learn about our organization, help to spread the word. I did a TED Talk that came out about a month ago. Spread the word about that. These are the kinds of things that actually, patients will benefit because we tweeted something. The work's already been done. The drugs are there, so just get in the word.

• 1:10:57Dax Shepard?

  Yeah, Mary, how often does your wife come? It's like, we gotta eat kale now. And you're like, how'd you find that out? My whole diet is based on whatever someone's told my wife. That is good for us now.

• 1:11:06Speaker 02

  Exactly.

• 1:11:07Dax Shepard?

  And then, of course, people should read your book, Chasing My Cure. It's wonderful. It's rare that I can say this to somebody, but I'm so happy you didn't make it in the NFL.

• 1:11:16Speaker 01

  Oh, my God.

• 1:11:16Dax Shepard?

  Congratulations on not going to the NFL. We needed you way more.

• 1:11:20Speaker 01

  And not getting CTE.

• 1:11:22Dax Shepard?

  I knew we wouldn't make it through.

• 1:11:26Speaker 01

  We're just lucky that you didn't get it because you wouldn't be able to do all this.

• 1:11:29Speaker 02

  Very true. Maybe there's a drug to repurpose.

• 1:11:32Speaker 01

  Exactly.

• 1:11:34Dax Shepard?

  David, this has been a delight, and I hope everyone does check out your book and checks out the website. And totally grateful this is the work you're doing. And every time we're getting really negative and pessimistic about AI, it's also doing this. It's like doing this shit humans could never do. Can't come through all that stuff. Thank you so much. Good luck with everything.

• 1:11:50Speaker 02

  Well, thanks for having me. This has been so special. Thanks, guys.

• 1:12:03Dax Shepard?

  Okay, so I have, I have huge Aaron updates.

• 1:12:06Speaker 01

  Okay.

• 1:12:06Dax Shepard?

  Okay, so Aaron was there for, I think, five days.

• 1:12:11Speaker 01

  He already went?

• 1:12:12Dax Shepard?

  He flew home this morning.

• 1:12:14Speaker 01

  Oh, wow. So he didn't fall down?

• 1:12:17Dax Shepard?

  Well, listen, um, in order, you know, each evening, I would FaceTime him.

• 1:12:25Speaker 01

  Okay.

• 1:12:25Dax Shepard?

  Uh, even before he started. And, um, I said, look, what, what's the game plan for this? Like the second story, um, Eve on the roof, you know? Uh, I said, you need to rent like a bucket? Do you, if you want to rent a bucket, you know, let me know, I'll figure that out. And he said, uh, no, I think I'm going, uh, I'm going harness and ropes.

• 1:12:45Speaker 01

  Okay, I like that. But what's that mean? You, you put yourself in kind of a diaper?

• 1:12:51Dax Shepard?

  Yeah, you put yourself in a leather diaper or a nylon diaper.

• 1:12:54Speaker 01

  You use a carabiner?

• 1:12:56Dax Shepard?

  Yeah, and then you hook off onto the roof.

• 1:12:59Speaker 01

  What, what, to what?

• 1:13:01Dax Shepard?

  Exactly. So the issue with the house in Nashville is it has a metal roof. So you can't do what he would have done when he was a roofer, which is like anchor it to the top, just screw into the wood.

• 1:13:10Speaker 01

  Oh.

• 1:13:11Dax Shepard?

  So he had to lasso the chimneys.

• 1:13:13Speaker 01

  What?

• 1:13:14Dax Shepard?

  Yes, but this, this plan wasn't, he, I think wisely, like I would have done. He just kept putting off the height.

• 1:13:23Speaker 01

  Sure.

• 1:13:24Dax Shepard?

  The really tall work.

• 1:13:25Speaker 01

  The hard part.

• 1:13:26Dax Shepard?

  He just kept like working in the yard and work, doing trees and doing like fences and stuff. And just, I think, eyeing all week. And, and so each night, but he's up and down a ladder. You know, he's doing a lot of ladder stuff.

• 1:13:37Speaker 01

  Oh, my God.

• 1:13:38Dax Shepard?

  And then I would look at the cameras at the house just to see if he was lying anywhere on the ground, you know?

• 1:13:43Speaker 01

  Mm-hmm.

• 1:13:44Dax Shepard?

  And then I would FaceTime him every night, which was so fun. A, just to have an excuse to have to FaceTime every single night.

• 1:13:50Speaker 01

  Yeah.

• 1:13:51Dax Shepard?

  It's a good, I want to make up a reason why I have to do that.

• 1:13:53Speaker 01

  I think you can just, friendship can be the reason.

• 1:13:55Dax Shepard?

  I know, but there's something more organic about it. It was like, okay, good, you're alive. And then I'd hear about everything he did that day. And, um, all right, so did you look at the pictures?

• 1:14:05Speaker 01

  Okay. I see him on top. Wow.

• 1:14:11Speaker 01

  This is so dangerous.

• 1:14:14Dax Shepard?

  Yes, Aaron looks, he looks like an ant on top of the roof.

• 1:14:18Speaker 01

  Who's taking these pics?

• 1:14:19Dax Shepard?

  Chris, the contractor happened to stop by for something else and he sees Aaron way on the top. Look at the one of Aaron crawling up.

• 1:14:26Speaker 01

  I know, that's so scary, Dax.

• 1:14:28Dax Shepard?

  I want him to almost be a decoration, like, wouldn't it be funny if there was a person, we had a person, like a dummy up there putting it on?

• 1:14:36Speaker 01

  Yeah.

• 1:14:36Dax Shepard?

  Um, okay, now if you go to the last picture in that group, do you see Aaron lying on the?

• 1:14:43Speaker 01

  Yeah, on the roof.

• 1:14:44Dax Shepard?

  Okay, so he did fall.

• 1:14:47Speaker 01

  No, no, no, no, no. Aaron, and by the way, he's not wearing the helmet, so he does not get $500 from me.

• 1:14:58Dax Shepard?

  Okay, but look how happy he is, zoom in on his face. This is textbook Aaron. So Aaron, he had this long rope, but the problem was is this, the chimney is not centered to where he needs to be on the high point. So he's using this rope kind of diagonally. And he's, in his mind, he's like, oh yeah, I mapped this out perfectly, like, if I fall, it's gonna catch me on the second story. Well, no, the rope was longer than he anticipated and he fell down to the first story. Um, but he did land right before he would have gone off the edge.

• 1:15:27Speaker 01

  On the ground, yeah.

• 1:15:28Dax Shepard?

  He is taught. I said, are you hurt? I was talking to him on my ride to my meeting last night. I said, you get hurt? And he goes, oh my God, no, I feel great. No problem. Then he sent me this picture about an hour later from the shower. I'm gonna send it to you. And this is, uh, this is from his harness.

• 1:15:46Speaker 01

  No, it's not, that's from his fall.

• 1:15:48Dax Shepard?

  Well, yeah, the harness, um, tightening when he fell.

• 1:15:52Speaker 01

  That looks horrible, he's hurt.

• 1:15:54Dax Shepard?

  I know, but he just doesn't care. But I also know what it's like to be him, which is like this, uh, this stuff just doesn't even register. It's like, I wanted to get those lights up there, I got them up there, I didn't really care about the thing. Okay, now watch the video coming into the house.

• 1:16:08Dax Shepard?

  And I'm gonna watch it with you. That's in fast forward. He's not really driving 100 in my neighborhood. He just wanted you to see what the neighbors have going before you saw what we have going.

• 1:16:17Speaker 01

  They do. Wait, that's yours?

• 1:16:20Dax Shepard?

  Yes.

• 1:16:21Speaker 01

  The yellow and the blue?

• 1:16:23Dax Shepard?

  Look at this place. It's like the Scanso Gardens.

• 1:16:27Speaker 01

  Oh my god.

• 1:16:30Dax Shepard?

  It's truly Clark Griswold.

• 1:16:33Speaker 01

  Wow, Aaron.

• 1:16:35Dax Shepard?

  Can you believe?

• 1:16:37Speaker 01

  He did such an amazing job.

• 1:16:39Dax Shepard?

  It's like an amusement park. Chris is like, you should charge $20 for people to walk through your yard this Christmas. Can you believe? I'm like, Aaron, no one has ever over-delivered this much. My expectations versus what he did.

• 1:16:51Speaker 01

  That looks so good. It looks stylized. Like, he like, he didn't just throw a bunch of shit everywhere.

• 1:16:59Dax Shepard?

  Right, and he put some real thought into it.

• 1:17:01Speaker 01

  Yeah, wow, good job, Aaron.

• 1:17:04Dax Shepard?

  Um, so for people who don't remember our custom for Thanksgiving with our friendship group.

• 1:17:09Speaker 01

  Yeah.

• 1:17:09Dax Shepard?

  We do something called Secret Turkey.

• 1:17:11Speaker 01

  Yes.

• 1:17:12Dax Shepard?

  I presume you've been assigned somebody?

• 1:17:13Speaker 01

  Yes.

• 1:17:14Dax Shepard?

  And have you been working on it yet?

• 1:17:15Speaker 01

  Yes.

• 1:17:16Dax Shepard?

  You have?

• 1:17:17Speaker 01

  I have. I finalized my idea yesterday and I, I put it a little bit into action. But there's a lot more steps and I'm nervous about running out of time.

• 1:17:26Dax Shepard?

  Cause is it, it's next week?

• 1:17:29Speaker 01

  Yeah, it's a week from Thursday.

• 1:17:31Dax Shepard?

  Okay, I gotta get cooking on mine too. I have, I have the base of mine.

• 1:17:35Speaker 01

  You do?

• 1:17:36Dax Shepard?

  And then I need to get artistic on top of it.

• 1:17:38Speaker 01

  I, you know, the rule is you have to make it.

• 1:17:41Dax Shepard?

  Okay.

• 1:17:42Speaker 01

  Right? Like, that's our rule?

• 1:17:43Dax Shepard?

  Yeah, yeah, yeah, yeah, yeah.

• 1:17:44Speaker 01

  And I feel like-

• 1:17:45Dax Shepard?

  Or customize something you love.

• 1:17:47Speaker 01

  So I feel like I'm blurring the line a little bit this year on that.

• 1:17:52Dax Shepard?

  Me too.

• 1:17:52Speaker 01

  A little. Okay, you too, too. Okay.

• 1:17:55Dax Shepard?

  Yeah.

• 1:17:55Speaker 01

  I wanna know who you have, but I don't wanna know.

• 1:17:58Dax Shepard?

  Yeah, I don't wanna know either. You like spoilers or not? Lincoln loves spoilers.

• 1:18:03Speaker 01

  Yeah, she loves that.

• 1:18:05Dax Shepard?

  I don't like it.

• 1:18:06Speaker 01

  I don't either.

• 1:18:07Dax Shepard?

  And she'll ask me, like, we're watching a movie I've already seen. And she's like, oh, what happens about it? And I'm like, I don't want to tell you.

• 1:18:12Speaker 01

  I know.

• 1:18:12Dax Shepard?

  You really want to know?

• 1:18:13Speaker 01

  Yeah.

• 1:18:13Dax Shepard?

  And she really wants to know.

• 1:18:15Speaker 01

  Yeah, must be anxiety in a movie or something, maybe?

• 1:18:19Dax Shepard?

  Yeah, or just impatience. I think more impatience.

• 1:18:22Speaker 01

  That's interesting.

• 1:18:23Dax Shepard?

  Yeah, I mean, that's a quality of mine, impatience, that I definitely think I passed on.

• 1:18:28Speaker 01

  But you do, you don't want to know.

• 1:18:31Dax Shepard?

  I don't, and that might be a product of getting older, which is there's so few surprises anymore.

• 1:18:35Speaker 01

  It's true.

• 1:18:36Dax Shepard?

  In life, you got to really kind of protect them. So like, I never want to know. I mean, I virtually don't even want to ever open presents on Christmas.

• 1:18:44Speaker 01

  Yeah.

• 1:18:45Dax Shepard?

  What I love is the anticipation of presents.

• 1:18:48Speaker 01

  I know, it is exciting.

• 1:18:49Dax Shepard?

  Yeah, post presents is...

• 1:18:51Speaker 01

  Sad.

• 1:18:52Dax Shepard?

  It's sad, yeah.

• 1:18:54Speaker 01

  Yeah.

• 1:18:54Dax Shepard?

  It's time to make up an excuse for why...

• 1:18:57Speaker 01

  You're going to Staples? Why you got to go to Staples? Um, yeah, because yesterday I walked in the house and Lincoln was there and she was working on something. And she was like, oh, I want to show you. And she showed me and it was her secret turkey.

• 1:19:10Dax Shepard?

  Yeah.

• 1:19:11Speaker 01

  And she was like, I have. And she said, and she said, who do you have? Like, with no, like, I know we're not supposed to say.

• 1:19:17Dax Shepard?

  No.

• 1:19:17Speaker 01

  Like, she just feels like we're gonna say it.

• 1:19:19Dax Shepard?

  That's right.

• 1:19:20Speaker 01

  I did tell her.

• 1:19:21Dax Shepard?

  You did?

• 1:19:21Speaker 01

  Yeah, because I felt kind of weird being like, no, I'm not, I'm not telling you.

• 1:19:25Dax Shepard?

  Yeah, she cornered you.

• 1:19:28Speaker 01

  Oh, I told her, and I told her my whole idea.

• 1:19:30Dax Shepard?

  Oh, you did?

• 1:19:31Speaker 01

  Yeah.

• 1:19:31Dax Shepard?

  Okay. Well, I'll make sure to not ask her. I'll make sure to not find out from her.

• 1:19:36Speaker 01

  Yeah, don't let her tell you about mine.

• 1:19:39Dax Shepard?

  Was it, no, it couldn't have been done, because when I got home last night from my meeting, she was just kind of finishing, and it was mind blowing.

• 1:19:44Speaker 01

  Ah.

• 1:19:45Dax Shepard?

  Like, I don't know what career exists in making dioramas, but boy, that is her, her crazy superpower.

• 1:19:52Speaker 01

  Skill.

• 1:19:52Dax Shepard?

  She makes so many dioramas.

• 1:19:54Speaker 01

  She's very artsy.

• 1:19:55Dax Shepard?

  And it has, the tree has lighting in it and stuff?

• 1:19:57Speaker 01

  I know, it's beautiful.

• 1:19:58Dax Shepard?

  Yeah.

• 1:19:59Speaker 01

  Yeah.

• 1:20:00Dax Shepard?

  I mean, her and Aaron, they could get together and really start a business.

• 1:20:03Speaker 01

  They could.

• 1:20:03Dax Shepard?

  She could make a model of your house.

• 1:20:05Speaker 01

  Yeah.

• 1:20:05Dax Shepard?

  What it'll look like when it's done. And then Aaron could execute it and then you get the model afterwards.

• 1:20:10Speaker 01

  I was just thinking that, then you have a small version of it inside.

• 1:20:12Dax Shepard?

  And it's like fifty-five thousand instead of.

• 1:20:15Speaker 01

  Instead of five?

• 1:20:16Dax Shepard?

  Because of the model.

• 1:20:17Speaker 01

  Oh, the, do you guys take down everything the day after Christmas?

• 1:20:22Dax Shepard?

  Oh, god, no.

• 1:20:23Speaker 01

  Okay, yeah, some people are like, it's over and we're done.

• 1:20:27Dax Shepard?

  Those, good for those people. No, you gotta go after New Year's, man.

• 1:20:30Speaker 01

  That's how I feel.

• 1:20:31Dax Shepard?

  You're gonna be entertaining and having people over. Okay, so, I have a correction to make.

• 1:20:36Speaker 01

  Okay.

• 1:20:36Dax Shepard?

  And this is, um, I'll take responsibility, even though I think we are on the same page with what the lyrics were.

• 1:20:44Dax Shepard?

  Dax, I was screaming in my car. The Nair lyrics are.

• 1:20:47Speaker 01

  Oh.

• 1:20:49Dax Shepard?

  Who wears short shorts? We wear short shorts. If you dare wear short shorts, Nair for short shorts.

• 1:20:59Speaker 01

  Nair for.

• 1:21:01Dax Shepard?

  And they're using Nair as a verb there, even though it is a, it is a noun, because it's a proper noun name of a product. They are using it as a verb. Nair for short shorts, Nair yourself.

• 1:21:11Speaker 01

  Or.

• 1:21:12Dax Shepard?

  Or sure, I guess it works both ways.

• 1:21:14Speaker 01

  Could still be the product.

• 1:21:15Dax Shepard?

  So it's not Nair wears short shorts.

• 1:21:17Speaker 01

  Okay, well, I'm, I guess I'm happy, because that didn't make any sense to us.

• 1:21:21Dax Shepard?

  I'm sad, I liked it more when it was Nair wears short shorts, as if Nair wears shorts.

• 1:21:26Speaker 01

  Yeah, I mean, I do think it's cute if there's little shorts on the bottle.

• 1:21:29Dax Shepard?

  Big time.

• 1:21:30Speaker 01

  That's adorable.

• 1:21:32Dax Shepard?

  But I do, I do appreciate, um, Taryn Graydell, um, correcting us.

• 1:21:37Speaker 01

  I like that. Do we think Nair is still on the market?

• 1:21:43Dax Shepard?

  Rob?

• 1:21:44Speaker 05

  Checking.

• 1:21:47Speaker 05

  Still have a website. Uh, yeah, it looks like it.

• 1:21:49Speaker 01

  Okay.

• 1:21:50Dax Shepard?

  Oh, great.

• 1:21:51Speaker 01

  I kinda feel like, allegedly, it had some, some, you know, some stuff in it that was like not so great.

• 1:22:01Dax Shepard?

  Well, if it's interesting, it burns your hair off your body, but it doesn't hurt your skin. What a product. You gotta give your, you gotta tip your hat to the folks at Nair that they figured out how to burn hair off your body without hurting your skin.

• 1:22:11Speaker 01

  I guess the question is.

• 1:22:13Dax Shepard?

  Does it?

• 1:22:13Speaker 01

  But does it hurt your skin?

• 1:22:14Dax Shepard?

  I remember using it once and it hurt my skin. Do you know what's so interesting about my uni brow?

• 1:22:20Speaker 01

  Yeah, what?

• 1:22:21Dax Shepard?

  Um, as I think it started coming in when I was like in

• 1:22:24Speaker 01

  Is that how you say it?

• 1:22:25Dax Shepard?

  High school uni brow? What do you say?

• 1:22:27Speaker 01

  I mean, it is.

• 1:22:28Dax Shepard?

  You know eyebrow?

• 1:22:28Speaker 01

  No, you're right, but it's just, it sounds cute the way you're saying it.

• 1:22:31Dax Shepard?

  Oh, okay.

• 1:22:32Speaker 01

  I think I'm like, oh, she is, have you seen her? She has a uni brow. Uni brow, I say uni brow.

• 1:22:37Dax Shepard?

  But that doesn't make sense, right? Cause there's no A in uni.

• 1:22:40Speaker 05

  That's how I say it, too.

• 1:22:41Dax Shepard?

  You say you know brow?

• 1:22:42Speaker 05

  Yeah, uni brow.

• 1:22:43Dax Shepard?

  Okay. And I want you guys to continue to say it that way, but I do think in this rare case, I'm saying it correctly and you guys are saying it incorrectly. Okay, the point is-

• 1:22:51Speaker 01

  But I think it's funny. Okay, go.

• 1:22:52Dax Shepard?

  Okay, my uni or e brow started coming in probably ninth grade or something. I started getting insecure about it.

• 1:22:58Speaker 01

  Yeah.

• 1:22:59Dax Shepard?

  And I started shaving it.

• 1:23:00Speaker 01

  Oh.

• 1:23:01Dax Shepard?

  Which is dicey. And a lot of boys shaved it in my school. And you can see them be stubble and it looks, it's terrible. So I was like, this doesn't work.

• 1:23:09Speaker 01

  Right.

• 1:23:10Dax Shepard?

  Cause you see it grow in.

• 1:23:11Speaker 01

  Yeah, yeah.

• 1:23:12Dax Shepard?

  And then I used Nair, I think.

• 1:23:13Speaker 01

  You did?

• 1:23:14Dax Shepard?

  Yeah, I think I did. And I remember my, in between my brows being very red and irritated. And me thinking, oh Jesus, do I have a, I have a burn now between? That's not better.

• 1:23:23Speaker 01

  You got a chemical burn.

• 1:23:24Dax Shepard?

  Chemical burn, yeah.

• 1:23:25Speaker 01

  Because this skin is so sensitive.

• 1:23:27Dax Shepard?

  Very thin.

• 1:23:28Speaker 01

  Face skin is extremely sensitive. It's like silk, they say.

• 1:23:31Dax Shepard?

  Is that what they say?

• 1:23:32Speaker 01

  They say, and you don't want to be pouring chemicals on silk.

• 1:23:35Dax Shepard?

  Never, never.

• 1:23:36Speaker 01

  Almost never.

• 1:23:37Dax Shepard?

  I never put Nair on my silk, even if I have a tough stubborn stain on my silk.

• 1:23:41Speaker 01

  Yeah, you don't want to. Now, you never, I guess like the boys in ninth grade weren't even thinking about plucking.

• 1:23:49Dax Shepard?

  No, so then I switched to plucking.

• 1:23:51Speaker 01

  Yes.

• 1:23:51Dax Shepard?

  In my, probably by the time I'm a senior or

• 1:23:55Speaker 01

  Okay.

• 1:23:56Dax Shepard?

  twenties or whatever.

• 1:23:57Speaker 01

  Mm-hmm.

• 1:23:58Dax Shepard?

  All this to say, Monica, I don't do anything to it now.

• 1:24:02Speaker 01

  And it's gone.

• 1:24:02Dax Shepard?

  It's fucking gone.

• 1:24:03Speaker 01

  Yeah.

• 1:24:04Dax Shepard?

  And it's been gone for a while.

• 1:24:06Speaker 01

  Yeah.

• 1:24:06Dax Shepard?

  And I'm so confused because hair is just proliferating all over my body in the most offensive way.

• 1:24:12Speaker 01

  Right.

• 1:24:12Dax Shepard?

  I told you, it's like when I work out, half my workout is seeing different hairs because the light's coming from behind me and I'm in front of a mirror.

• 1:24:19Speaker 01

  Sure.

• 1:24:20Dax Shepard?

  I'm like, my God, I'm turning into a werewolf.

• 1:24:22Speaker 01

  Yeah.

• 1:24:23Dax Shepard?

  Um, but for whatever reason, the uniture, the middle part of the uni brow.

• 1:24:28Speaker 01

  Yeah.

• 1:24:29Dax Shepard?

  Went away in, in, in an era of great, great hair growth.

• 1:24:33Speaker 01

  So I agree though, even for me, like.

• 1:24:38Dax Shepard?

  Have you had that experience?

• 1:24:39Speaker 01

  Yeah, it, I mean, every now and then I'll like have to like pluck a little bit, especially on the sides, but the middle is.

• 1:24:45Dax Shepard?

  Is free.

• 1:24:46Speaker 01

  Done. Yeah.

• 1:24:47Dax Shepard?

  And it used to have some action?

• 1:24:48Speaker 01

  Yeah.

• 1:24:49Dax Shepard?

  Yes.

• 1:24:49Speaker 01

  I think there is, is something to when you pluck a lot.

• 1:24:54Dax Shepard?

  They give up.

• 1:24:55Speaker 01

  An area, yeah.

• 1:24:56Dax Shepard?

  They give up.

• 1:24:57Speaker 01

  They give up. That's why people were so worried, you know, girls of my gen would over pluck our eyebrows like crazy. And it was just this like teeny tiny thin line. That was what was in.

• 1:25:09Dax Shepard?

  Yeah.

• 1:25:09Speaker 01

  And then there was a lot of fear once bushier eyebrows were back in, they would never come back.

• 1:25:15Dax Shepard?

  Right. But they did.

• 1:25:17Speaker 01

  They kind of did.

• 1:25:18Dax Shepard?

  Yeah.

• 1:25:19Speaker 01

  For me, anyway. But yeah, the, the uni is.

• 1:25:22Dax Shepard?

  Retired. It'll retire.

• 1:25:24Speaker 01

  It retired.

• 1:25:24Dax Shepard?

  I wonder why it thinks you needed in your youth and not in your old age. Must have been a very attractive thing at some point.

• 1:25:31Speaker 01

  Maybe.

• 1:25:32Dax Shepard?

  It showed your virility or something.

• 1:25:34Speaker 01

  Well, testosterone.

• 1:25:36Dax Shepard?

  Sure. Tea.

• 1:25:38Speaker 01

  Very virile.

• 1:25:39Dax Shepard?

  Yeah.

• 1:25:39Speaker 01

  Interesting.

• 1:25:40Dax Shepard?

  But mine's gone.

• 1:25:41Speaker 01

  Do you think, yeah, at one point, like the female unibrow was considered hot?

• 1:25:47Dax Shepard?

  Yeah.

• 1:25:47Speaker 01

  I guess Frida.

• 1:25:48Dax Shepard?

  Frida.

• 1:25:49Speaker 01

  She was hot.

• 1:25:50Dax Shepard?

  Yeah. May almost had it and she looked great. Like she would, she would on parenthood, she had bushy eyebrows and she would comb them towards each other.

• 1:25:58Speaker 01

  Oh, yeah, yeah, yeah.

• 1:25:59Dax Shepard?

  And it looked so cute.

• 1:26:00Speaker 01

  Yeah, yeah.

• 1:26:02Dax Shepard?

  You just, I mean, you really, the power to decide you're cute and it's infectious is really one of the miracles on earth.

• 1:26:09Speaker 01

  What if they start doing like, um, implants? Yeah, merkin.

• 1:26:28Speaker 01

  Okay, we gotta talk about it.

• 1:26:29Dax Shepard?

  Okay.

• 1:26:30Speaker 01

  Skims has a merkin.

• 1:26:33Dax Shepard?

  Yeah, tell me more. Tell me all about it.

• 1:26:36Speaker 01

  Skims has a thong. The front is covered in hair.

• 1:26:42Dax Shepard?

  Okay.

• 1:26:42Speaker 01

  And then there's different colors and there's different textures. There it is.

• 1:26:46Dax Shepard?

  Interesting, so blue is an option.

• 1:26:48Speaker 01

  Well, I think that's black, isn't it?

• 1:26:51Dax Shepard?

  Okay. Photographed a little blue, but that's okay.

• 1:26:53Speaker 01

  It did.

• 1:26:54Dax Shepard?

  And the other one looks like camel hair.

• 1:26:55Speaker 01

  Yeah, one's red. I don't really understand that.

• 1:26:58Dax Shepard?

  Well, that's red on the head, fire in the hole.

• 1:27:00Speaker 01

  Oh, that's a redhead.

• 1:27:02Dax Shepard?

  The curtains.

• 1:27:03Speaker 01

  Absolutely. See how they're different textures? Like, one's curly, one's straight, one's like fuzzies.

• 1:27:09Dax Shepard?

  Yes.

• 1:27:10Speaker 01

  By the way, you can't, you can't get any of these.

• 1:27:13Dax Shepard?

  Oh, you can't?

• 1:27:14Speaker 01

  No, they're all sold out, which I find, I have to be, I love Skims. And I want them to send this to me.

• 1:27:22Dax Shepard?

  Yeah, send it to Monica. I was gonna say, I wanna see someone in, obviously not you. That would be in the realm of, what was the, what were you gonna?

• 1:27:30Speaker 01

  Oh, yeah.

• 1:27:31Dax Shepard?

  Put your thumb in my butt to save my life? As a coworker?

• 1:27:38Speaker 01

  The things we talk about.

• 1:27:40Dax Shepard?

  Yeah, yeah. So, yeah, I wanna see someone in this, maybe Rob.

• 1:27:45Speaker 01

  Okay.

• 1:27:45Dax Shepard?

  See Rob in this.

• 1:27:47Speaker 01

  I think you should see Kristen in it.

• 1:27:49Dax Shepard?

  Yeah.

• 1:27:49Speaker 01

  Cause that's the best case to know if, like, it actually.

• 1:27:52Dax Shepard?

  Is erotic.

• 1:27:53Speaker 01

  Yeah.

• 1:27:53Dax Shepard?

  Yeah.

• 1:27:54Speaker 01

  It says it's an actual pair of underwear. I mean.

• 1:27:57Dax Shepard?

  Anything's erotic.

• 1:27:58Speaker 01

  It's called faux hair micro string thong. It's totally sold out.

• 1:28:03Dax Shepard?

  Yeah.

• 1:28:03Speaker 01

  I would like Skims to send me one. Now, I do have a question. Like, I've never seen.

• 1:28:13Speaker 01

  A redheaded pubes.

• 1:28:15Dax Shepard?

  Uh huh.

• 1:28:16Speaker 01

  Would it possibly be that red?

• 1:28:19Dax Shepard?

  No.

• 1:28:19Speaker 01

  It wouldn't, right?

• 1:28:20Dax Shepard?

  Well, I've had some redheaded lovers.

• 1:28:23Speaker 01

  Yeah.

• 1:28:23Dax Shepard?

  And I've had the great pleasure and joy of seeing red pubes.

• 1:28:27Speaker 01

  Uh huh.

• 1:28:28Dax Shepard?

  They're lovely.

• 1:28:29Speaker 01

  But aren't they more orange?

• 1:28:30Dax Shepard?

  Yeah.

• 1:28:31Speaker 01

  Okay, that would be my guess. Even red hair isn't that color.

• 1:28:35Dax Shepard?

  No, unless it's been augmented.

• 1:28:37Speaker 01

  Okay, the one I would be, I think I should try.

• 1:28:41Dax Shepard?

  Yeah.

• 1:28:41Speaker 01

  Is, um.

• 1:28:42Dax Shepard?

  Well, blonde though, that's kind of mixed messages.

• 1:28:45Speaker 01

  It's like fun mixed messages.

• 1:28:47Dax Shepard?

  Yeah, yeah.

• 1:28:47Speaker 01

  They have like a white blonde one. They also have, let me look. Let me see what I want.

• 1:28:52Dax Shepard?

  Okay.

• 1:28:52Speaker 01

  I want two. I want, I want three.

• 1:28:57Dax Shepard?

  Okay, great.

• 1:28:57Speaker 01

  I want the cocoa blonde straight.

• 1:29:00Dax Shepard?

  Mm hmm.

• 1:29:01Speaker 01

  That's this.

• 1:29:03Dax Shepard?

  Oh yeah, great, exciting.

• 1:29:05Speaker 01

  Okay, then I want cocoa ginger curly.

• 1:29:11Dax Shepard?

  Oh, sure.

• 1:29:13Speaker 01

  Okay.

• 1:29:13Dax Shepard?

  Okay.

• 1:29:14Speaker 01

  Then I'm interested in cocoa brown straight.

• 1:29:19Dax Shepard?

  That's the bottom one there.

• 1:29:20Speaker 01

  Yeah.

• 1:29:21Dax Shepard?

  That one looks a little coarse, doesn't it though? Like horse hind?

• 1:29:24Speaker 01

  It does, but to me that looks the most real.

• 1:29:28Dax Shepard?

  Mm hmm.

• 1:29:28Speaker 01

  But it's not my coloring, so I think that'd be interesting.

• 1:29:31Dax Shepard?

  Yeah, that could be fun for people. Keep them guessing.

• 1:29:34Speaker 01

  And I, this one is closest to me, that, that middle one, cocoa black curly.

• 1:29:41Dax Shepard?

  Uh huh, so that's what you want? Oh wow, Rob. We have a real extra close up of the.

• 1:29:49Speaker 01

  The brown hair.

• 1:29:50Dax Shepard?

  It looks beautiful.

• 1:29:51Speaker 01

  It looks itchy, yeah.

• 1:29:53Dax Shepard?

  It looks like hay, stabby.

• 1:29:55Speaker 01

  It really looks like pointy.

• 1:29:57Dax Shepard?

  Well, you'll, send those to Monica and then we'll get a full update on.

• 1:30:00Speaker 01

  Yes, please send me these. Cocoa black curly I would like because I want to see how realistic it is.

• 1:30:06Dax Shepard?

  Well, there's got little hints of gray hair in there.

• 1:30:08Speaker 01

  I know, that's.

• 1:30:09Dax Shepard?

  That's fun.

• 1:30:10Speaker 01

  No.

• 1:30:11Dax Shepard?

  Elderly.

• 1:30:12Speaker 01

  That will depress me. Um.

• 1:30:15Dax Shepard?

  People's pubic hair does turn gray.

• 1:30:17Speaker 01

  I know, I've heard that.

• 1:30:19Dax Shepard?

  Mine hasn't, yeah, luckily. Still look youthful.

• 1:30:22Speaker 01

  Wow, will you let us know when yours starts to turn?

• 1:30:25Dax Shepard?

  Turn gray?

• 1:30:25Speaker 01

  Yeah.

• 1:30:26Dax Shepard?

  Be a sad day, I'll report it. There's that old allegory, there's a very famous story right about a king with one gray hair. Soon as you get a gray hair, you can no longer be king. Do you know this? It's a very famous story.

• 1:30:36Speaker 01

  I don't know it. I don't know it. What happens?

• 1:30:39Dax Shepard?

  He's either, well, he can't be king anymore, and he might even have to die, I don't know.

• 1:30:43Speaker 01

  Oh!

• 1:30:43Dax Shepard?

  Or he turns it over to his son immediately when there's a gray hair. So he's living in this great fear of one gray hair.

• 1:30:49Speaker 01

  Oh.

• 1:30:50Dax Shepard?

  Yeah, and it teaches you some kind of lesson, but I don't know what it is.

• 1:30:53Speaker 01

  It feels like you should be afraid if you're gonna get killed or dethroned.

• 1:30:57Dax Shepard?

  Yeah, it's a legitimate fear, yeah. But it's supposed to teach you an important lesson.

• 1:31:01Speaker 05

  Uh, messenger of death sent by the god of death. And the king immediately understands the implication is youth, middle age, and old age are coming to an end, and death is imminent.

• 1:31:12Dax Shepard?

  Ooh.

• 1:31:13Speaker 01

  I still don't understand the lesson.

• 1:31:15Speaker 05

  Uh, the core moral of the story is that even a long life is too short to waste on mere worldly pleasures and power. One must recognize the signs of aging and mortality and dedicate oneself to a life of wisdom and righteousness.

• 1:31:27Dax Shepard?

  Ah.

• 1:31:29Speaker 01

  Interesting.

• 1:31:29Dax Shepard?

  Okay, wow, this is a ding ding ding. This is really ringing a bell.

• 1:31:33Speaker 01

  Ooh, okay.

• 1:31:34Dax Shepard?

  Okay, so my weekend, now I'm gonna violate it, but I'm not really violating it. You might think I'm violating it, but I swear I'm not.

• 1:31:41Speaker 01

  Okay.

• 1:31:42Dax Shepard?

  Because I'm not telling any of the people involved, and that's the key.

• 1:31:45Speaker 01

  Okay.

• 1:31:45Dax Shepard?

  And no one involved in this will listen to this, nor will it get to them. So my weekend was 100% of service.

• 1:31:54Speaker 01

  Great.

• 1:31:54Dax Shepard?

  We had a thing on Friday night, I had to drive to sit through, I had a volleyball game, then I had a birthday party, I had to drive someone out there, then I'd sit in my car for an hour and a half while someone was at a birthday party. Then there was a show, a thing, I mean, it was the whole weekend. And I, I found myself wanting to call attention to what a sacrifice I had been making. That was my instinct, and that I, I wanted it to be known that I hadn't done anything I wanted to do this weekend.

• 1:32:20Speaker 01

  Right.

• 1:32:21Dax Shepard?

  And I remembered my great therapist Mark telling me, um, listen, as a man, you can think this, but you shan't say this. You shan't ever say, what about me?

• 1:32:34Speaker 01

  Mm-hmm.

• 1:32:35Dax Shepard?

  And that's solid advice for a man.

• 1:32:37Speaker 01

  I like that.

• 1:32:38Dax Shepard?

  Yeah, it's, it's the path we need to walk, us men, and it should be walked. And I just kept hearing the voice in my head all weekend like, you're not gonna mention at all that you haven't done anything but drive people around on your limited two days off.

• 1:32:54Speaker 01

  Yeah.

• 1:32:55Dax Shepard?

  And I achieved that goal. And then on the flip side of the coin was I had done something abnormally generous for me, for virtually a stranger.

• 1:33:04Speaker 01

  Okay.

• 1:33:05Dax Shepard?

  And then I was like, and you can't tell anyone. And I was like, I'm gonna call my mom and tell her. That's what I wanted to do.

• 1:33:13Speaker 01

  Great.

• 1:33:14Dax Shepard?

  Like, I'm not gonna tell any of my friends I did this.

• 1:33:16Speaker 01

  Great.

• 1:33:16Dax Shepard?

  I don't want my children to know. Kristen had to know because we share finances.

• 1:33:22Dax Shepard?

  And I had to talk myself out of.

• 1:33:25Speaker 01

  Telling your mom?

• 1:33:25Dax Shepard?

  Telling my mom. And I decided, it's, you're old man, it's time to stop doing anything.

• 1:33:32Speaker 01

  Looking for.

• 1:33:33Dax Shepard?

  And so that you'll be observed doing it. Applause, validation.

• 1:33:39Speaker 01

  Yeah.

• 1:33:40Dax Shepard?

  We love you, you're so good. When is it just gonna be for you? Why don't you just do things that you know give you esteem and leave it at that? That's a hard challenge for me. I'm embarrassed to admit.

• 1:33:53Speaker 01

  Yeah.

• 1:33:53Dax Shepard?

  Like, to do things secretly that only fill me up and only I know were good.

• 1:33:58Speaker 01

  Right.

• 1:33:59Dax Shepard?

  Is, is the, I think, the last chapter you should, I should hope to achieve.

• 1:34:04Speaker 01

  Yeah, that's great.

• 1:34:05Dax Shepard?

  On my evolution on this planet. But that, that reading just made me think of that entirely. Like, it's time for wisdom, it's time for other things.

• 1:34:13Speaker 01

  Oh, that came.

• 1:34:14Dax Shepard?

  And for me and my life, it's time to just do things.

• 1:34:18Speaker 01

  Yeah.

• 1:34:19Dax Shepard?

  Quietly for me.

• 1:34:20Speaker 01

  Yeah.

• 1:34:21Dax Shepard?

  And it's almost, it feels pointless, which is crazy. That's how deep the exhibitionism of my soul is.

• 1:34:30Speaker 01

  It feels pointless to help.

• 1:34:32Dax Shepard?

  If I only know.

• 1:34:34Speaker 01

  Oh, wow.

• 1:34:35Dax Shepard?

  I mean, it doesn't feel pointless to the person that I help, of course.

• 1:34:39Speaker 01

  Yeah, exactly. That should be enough.

• 1:34:41Dax Shepard?

  But opening my imagination to a world where no one ever knows if I did something good.

• 1:34:48Speaker 01

  Yeah.

• 1:34:48Dax Shepard?

  Is shockingly absent of the normal reward I'm.

• 1:34:54Dax Shepard?

  Used to giving or the, just the operation.

• 1:34:58Speaker 01

  Yeah.

• 1:34:59Dax Shepard?

  Um, I don't know, it's really tripping me out.

• 1:35:01Speaker 01

  Yeah, that's a great goal.

• 1:35:03Dax Shepard?

  Yeah, and it's harder than I want it to be.

• 1:35:06Speaker 01

  Yeah, but this kind of circles back to something we talked about a few weeks ago, the give for fun and for free.

• 1:35:12Dax Shepard?

  Uh huh.

• 1:35:12Speaker 01

  That's what it is about.

• 1:35:14Dax Shepard?

  I know, I know. I guess, like, I don't feel very judgmental of myself because like, look, again, we're, we're like this super social animal and our reputation is everything in, in a group.

• 1:35:27Speaker 01

  Yeah.

• 1:35:28Dax Shepard?

  Are you benevolent or are you selfish? Like, these are key things we need to know about each other if we're gonna trust each other. So naturally, we want people to see when we're benevolent.

• 1:35:38Speaker 01

  I know.

• 1:35:38Dax Shepard?

  And we pray they don't see when we're selfish and shitty.

• 1:35:41Speaker 01

  Yes.

• 1:35:42Dax Shepard?

  Because we have to keep our standing in our group.

• 1:35:45Speaker 01

  I know, but I guess the, the-

• 1:35:47Dax Shepard?

  It's like life or death.

• 1:35:48Speaker 01

  The catch 22 of it though, and this isn't fair, but this is true, is displaying you're benevolent or generous, like stating it-

• 1:35:59Dax Shepard?

  Uh huh.

• 1:36:00Speaker 01

  Has the opposite effect.

• 1:36:01Dax Shepard?

  Uh huh, yeah.

• 1:36:02Speaker 01

  It makes people think like, no, you're not, because you had to do that. Like, like, it takes away from the act itself. I think people, I think-

• 1:36:10Dax Shepard?

  Well, there's some artistry to it. There is a way for people, for you to let people find out stuff you've done that's good, that isn't overtly braggy. Like, if someone's overtly braggy, yeah, it's immediately distasteful. But if you find out that Eric put a kid through college.

• 1:36:28Speaker 01

  Yeah.

• 1:36:29Dax Shepard?

  You're like, super proud of Eric.

• 1:36:30Speaker 01

  That's amazing, yeah.

• 1:36:31Dax Shepard?

  Yeah, and you would want to say to him, like, that was rad, dude, I'm glad you did that.

• 1:36:34Speaker 01

  Yeah.

• 1:36:35Dax Shepard?

  And so there's a way for Eric to get that out that's not gross.

• 1:36:38Speaker 01

  But I don't think so. Like, I, I think if he has a hand in saying it, it does take away. I think though, I, I think people would do find out, whether you say it or not.

• 1:36:51Dax Shepard?

  Yeah.

• 1:36:51Speaker 01

  People will find out people, other people's level of generosity, whether they are affected or not, or told or not.

• 1:37:01Dax Shepard?

  Uh huh.

• 1:37:02Speaker 01

  It's- I don't know. I think it's clear.

• 1:37:05Dax Shepard?

  Yeah.

• 1:37:05Speaker 01

  And it way more clear when the person is keeping it to themselves.

• 1:37:11Dax Shepard?

  Yeah, it's just, it's a really powerful force.

• 1:37:14Speaker 01

  Yeah.

• 1:37:14Dax Shepard?

  To do things secretly.

• 1:37:17Speaker 01

  Yeah. It's a good goal.

• 1:37:18Dax Shepard?

  It is.

• 1:37:19Speaker 01

  I like it.

• 1:37:20Dax Shepard?

  And it's ju- but again, so me saying that there seems to be no reward on the other side of it is also me saying like, oh, this is interesting because I know there is a reward, but I can't even imagine it.

• 1:37:33Speaker 01

  Yeah.

• 1:37:33Dax Shepard?

  Which is interesting and fun because I'm so locked into this architecture of like, people approve of you.

• 1:37:42Speaker 01

  Yeah, the reward.

• 1:37:43Dax Shepard?

  Doing the right thing. It's like, people approve of you.

• 1:37:47Speaker 01

  Yeah, the reward is that you know you're good.

• 1:37:50Dax Shepard?

  Right. And that's where they think the growth is, is that why, why don't I value it all if I think I'm good?

• 1:37:56Speaker 01

  Yeah, exactly. Why do you need other people to know, to think it if you know it's true?

• 1:38:01Dax Shepard?

  Yes. Why doesn't my opinion about myself matter at all? Unless it's negative, then I think it's very important.

• 1:38:07Speaker 01

  Right, right, right.

• 1:38:09Dax Shepard?

  Self-flagellating, I think I'm the, I'm the most astute observer of me in the world.

• 1:38:12Speaker 01

  Right.

• 1:38:13Dax Shepard?

  And so, yeah, I think I am going into it with a blind faith that one day I'll wake up and go, oh, this is the reward and I love it. But it is a bit of a blind faith pivot.

• 1:38:26Speaker 01

  Yeah, I like that.

• 1:38:26Dax Shepard?

  I think I've been slowly moving in that direction before whatever this re- this weekend just was like compounded. Two things I would have normally done is like call my mom.

• 1:38:36Speaker 01

  Yeah.

• 1:38:38Dax Shepard?

  Mommy, I was a good boy.

• 1:38:41Speaker 01

  I think.

• 1:38:41Dax Shepard?

  I turned out to be good like you hoped I would be.

• 1:38:46Speaker 01

  I think of all the people to tell your mom.

• 1:38:49Dax Shepard?

  Is safest.

• 1:38:50Speaker 01

  Yeah.

• 1:38:51Dax Shepard?

  Which is why it was hard to talk myself out of.

• 1:38:53Speaker 01

  Right.

• 1:38:54Dax Shepard?

  Yeah.

• 1:38:55Speaker 01

  Yeah, I think you would, you could have done that.

• 1:38:56Dax Shepard?

  No, I'm gonna, I'm not gonna.

• 1:39:00Speaker 01

  Well, that's great. Um, all right, let's do some facts. Okay. David Fajgenbaum, um, I only have one fact. He was extremely factual.

• 1:39:13Dax Shepard?

  He sure was.

• 1:39:14Speaker 01

  The only thing I did look up was, does glioblastoma affect women more than men?

• 1:39:20Dax Shepard?

  Oh, yeah.

• 1:39:21Speaker 01

  It's more common in men than women.

• 1:39:23Dax Shepard?

  Oh, my God. Well, this is, this is why anecdotal info is misleading. It just so happens in my life, I've known a lot of women.

• 1:39:30Speaker 01

  Yeah.

• 1:39:30Dax Shepard?

  And none men.

• 1:39:32Speaker 01

  Men are about 60% more likely to develop the tumor. While the exact reasons are still being researched, this disparity is not believed to be solely due to sex hormones. Anyway, it's very, it's not fully understood.

• 1:39:47Dax Shepard?

  It's horrific. I know that part.

• 1:39:48Speaker 01

  I know, I know. It's because, so unfortunately, one of our very good friends has had multiple people affected by this, died of it. She once taught me that like, it's like the shape of the tumor. It has like, kind of spikies.

• 1:40:11Dax Shepard?

  What are those?

• 1:40:11Speaker 01

  Which make it hard to remove.

• 1:40:12Dax Shepard?

  Oh, what are those kind of, they look like caulflowers, but they're pointy at the end? Yeah, they're beautiful.

• 1:40:19Speaker 01

  Yeah, um, they're green normally.

• 1:40:22Dax Shepard?

  Yeah, uh-huh, they're beautiful.

• 1:40:23Speaker 05

  Romanesco cauliflower.

• 1:40:26Dax Shepard?

  Romanesco what?

• 1:40:27Speaker 05

  Cauliflower.

• 1:40:27Dax Shepard?

  Cauliflower. God, is that impossibly gorgeous. Nature, let's all give it up. Round of applause for nature. Isn't that impossibly beautiful?

• 1:40:35Speaker 01

  It looks like tiny Christmas trees.

• 1:40:37Dax Shepard?

  Tiny Christmas trees, also coral, sea coral.

• 1:40:40Speaker 01

  It is wild that nature made that.

• 1:40:42Dax Shepard?

  Yeah.

• 1:40:43Speaker 01

  And like, nature makes pineapples, like, that's crazy.

• 1:40:46Dax Shepard?

  And the symmetry you see, and crystals, and all these things, like the shapes it can make.

• 1:40:52Speaker 01

  Yeah. It's pretty cool.

• 1:40:54Dax Shepard?

  I'm really grateful for you, nature. I hope you're a listener.

• 1:41:00Speaker 01

  Oh, one other thing I did look up because he talked about folic acid for nonverbal autism. So when I got diagnosed with epilepsy.

• 1:41:11Dax Shepard?

  Yeah.

• 1:41:12Speaker 01

  He told me, so I got put on the Kepra. My doctor, my neurologist, great man. Dr. Steven Sykes, love him.

• 1:41:20Dax Shepard?

  Beautiful man.

• 1:41:21Speaker 01

  Beautiful man. He said if I'm thinking about getting pregnant ever, that I should take folic acid. Being on this medication and having epilepsy.

• 1:41:31Dax Shepard?

  Okay.

• 1:41:32Speaker 01

  I didn't really know why. He probably told me, but my brain was a little fucked up. So then I just looked. Should you take folic acid if you have epilepsy? Yes, people with epilepsy, especially women of childbearing age, should take folic acid. Uh, but the appropriate dose must be determined with a doctor. Prevents neural tube defects and other birth defects in children. And can also be deficient in those taking certain anti-epileptic drugs.

• 1:41:59Dax Shepard?

  I take it and I don't have epilepsy.

• 1:42:01Speaker 01

  Oh, you do?

• 1:42:01Dax Shepard?

  Yeah, it's part of my regime.

• 1:42:03Speaker 01

  You like the taste?

• 1:42:04Dax Shepard?

  No, I don't like any of it. I constantly am complaining at night. It takes me like 30 minutes extra to go to bed because of all the stuff I'm doing to try to stay alive longer. And I lament it. I'm like, God, it's a lot of work to stay.

• 1:42:18Speaker 01

  And you're actually taking time out of your life. What if we added up the amount of time you're taking?

• 1:42:23Dax Shepard?

  I would rather have the TV time.

• 1:42:24Speaker 01

  Ah.

• 1:42:25Dax Shepard?

  All right, love you.

• 1:42:25Speaker 01

  All right, love you.