Transcript of #240 Dr. David Fajgenbaum - Can AI Find Cures to Rare Diseases Using Existing Medicine?

Dr. David Fagenbaum.

John, thanks for having me.

Welcome to the show.

Thanks for having me.

Hey, my pleasure. Wow, you've had quite the journey with health, and you made some amazing discoveries. I don't know a whole lot about it, but we're going to dive into all that. But thank you for coming. I'm really excited about this. One of my biggest fears, probably my biggest fear, is terminal illness. We started diving into health stuff last year, primarily about all the stuff you were hearing on the news about red dyes and all the shit that's in foods and the water and just everything. It really got my attention. I've been looking for somebody on the subject of cancer You're right there. This is something, a subject I've been wanting to dive into for a long time. I just really appreciate your time and coming here.

I'm so happy to be here and looking forward to this conversation. Cool.

Well, everybody starts off with an introduction here.

Nice.

David Fagenbaum, Trailblazing physician, scientist, and tenured professor at University of Pennsylvania's Perelman School of Medicine. Channeled your expertise in immunology and drug repurposing tackle some of the world's most elusive diseases. Founder of the Castleman disease Collaborative Network to accelerate breakthroughs for rare hyperinflammatory disorder that nearly claimed your life five times. Co founder of EveryCure an innovative nonprofit harnessing AI to repurpose existing drugs and unearth hidden treatments for untreatable conditions. Best-selling author of Chasing My Cure that chronicles your journey and is now being turned into a film. A Ted speaker who's 2025 talk, How Nearly Dying Helped Me Discover My Own Cure, and many more, has ignited a movement to change medicine. A husband, a father, and now living over a decade in remission from Castlements. You have a great quote that I just wanted to share. The greatest cures often hide in drugs we already have. It's up to us to find them.

That's right.

Love that quote. Love that quote. I want to do a bit of a personal story on you, a life story on how this all happened. I know you were a hell of a collegiate athlete when you got diagnosed, correct? We'll start there and then go through all your research, how you cured yourself and all that good stuff. But first, we got a couple of things to knock out. That's good. Kind of funny because I was just talking about red dyes. But here's a bag of Vigilance League gummy bears made here in the USA, no funny business, no THC, no CPD. It's just candy with all the horrible shit that comes along with candy, but they taste amazing.

My kids are going to love this.

Right on. Then one other thing, I got a Patreon account. They've been with us since the beginning. It's a subscription account, and we've turned it into one hell of a community over the years. They've been with me forever. One of the things that we do is we offer them the opportunity to ask each and every guest a question. This is from Stephen Casey. What roadblocks exist in the current medical establishment to the types of breakthroughs like yours? And what can the average person do to advance ideas like repurposed treatments, off-label use, experimental use to change the industry that seems locked in tradition.

Yeah. I mean, the biggest roadblock is that the drugs that we already have, 80% of them are generic, which means it's not profitable to find a new use for them. And so no one's going to advance those nonprofitable opportunities. So if someone's got to do it, as you said earlier, we're going to do that. But what can you do as he asked? You can ask your doctor, Is there anything else that maybe is a proof for one other disease that can maybe help my condition connect with disease organizations for whatever the condition is that you or your loved one has? They oftentimes know about these other medicines could be used, and then just be relentless. If your first doctor tells you that they're not going to help out or be able to get you that medicine that might help you go see someone else.

While we're on the subject of doctors, in my opinion, the healthcare industry is just a complete disaster. I don't know exactly how it works, so I might butcher this a little bit, but you get an insurance policy, and then they have all these doctors in network. You go to those doctors, and it's like they just rush to get you out of there. One thing that me and my family have done is we found... I don't even know what you call it, but it's like...

The concierge doctor?

Yeah, it's like... I think that's what it is. They don't take insurance. You have to pay out of pocket to do it. But a lot of people, they don't have the means to do that. I switched because I'm getting older, I'm over 40 now. I know shit It's going to start happening to me. The big thing I noticed is if I bring my blood test into an in-network typical MD, they look You get it for about 20 seconds. They're like, Oh, everything looks good. Then you take it to another professional, an MD, who doesn't take insurance, and they go through it line by line by line, tell you everything that's going on, order more tests, get more blood tests, go get the... They're very proactive. And so not just for people that don't have the means, but how do people find a real doctor when they have terminal illness has come up? I would imagine you're in a hurry to find somebody.

It's the right question. I think that you're right. I think that some of these concierge doctors, they definitely put more time and effort in them. That's part of the value you get from seeing one of those doctors. But I'd also say even outside of that, just within the traditional insurance system, there are some amazing doctors out there, but you got to find them. The chance of that, the most amazing doctor for your disease is down the street from you is probably pretty low. If you've got a bad cancer or a bad rare disease, you might need to get in your car and drive to find that person. I think that when we get sick, we all want our doctor, our local doctor, whoever to have all the answers for us, to be able to take care of us. But for a lot of these really bad diseases that are really hard to figure out, sometimes you got to find the expert and you got to take that extra step that you don't want to take. You want to trust your local doctor. But I think that sometimes you got to do that extra step to find the right person for you.

Could you elaborate on that just a little bit? Sure. I mean, for those of us that have very limited knowledge in health care at all, let alone specific diseases, is that a Google search? Is Is that an AI search? How does an uneducated person in the health care industry know what they're looking at? Where do they even start to find a good doctor?

I think the first thing is a Google search. Whatever your disease is throw that into Google, maybe throw in disease organization because there might be an organization for that disease. You can call someone, and all they think about is that disease. They've got a kid with the disease or they have it themselves. Start on Google, talk to that group, and They will almost always have a few great doctors they know of that know so much about it. I think that that's the key thing for some of these really tough diseases. They're really tough to treat. You really want to find someone who's got that experience. In some cases, In my case, even the world's expert didn't have an answer for me because the world didn't have an answer for how to treat my disease. That's obviously a situation you don't want to be in.

All right. Thank you for that. Absolutely. Let's move into your story. Sure. Where did you grow up? What were you doing?

Grew up in Raleigh, North Carolina. Youngest of three. I got two amazing older sisters. From the time I was about eight or nine years old, I set my mind on I wanted to be a college quarterback, a division one quarterback. That became my thing. I grew up in Raleigh, where NC State, UNC, and UNC, and Duke, and those schools around there. That became just my total obsession. I had just like how you got this amazing stuff on your walls, I had poster boards on my walls with how fast my 40-yard time was, how far I could throw a football. That just became all I could think about. From the time I was about eight until I was 18, I wanted to play college football, wanted to be a quarterback somewhere. That was all I worked on. I just worked day and night. Then had the opportunity. Got recruited by a bunch of Ivy League schools and Patri League schools. Ended up choosing to go to Georgetown for college.

Nice.

Which you probably didn't know we had a football team at Georgetown. We do have a football team at Georgetown. Right on. We do.

What was going on when you got diagnosed?

Well, so for me, the big change-Misdiagnosed.

Yes. Misdiagnosed.

Yes, misdiagnosed. Actually, even before that, there was this major change. I got to Georgetown. It's like, I achieved this dream, going to play college football. A couple of weeks after I got there, I got this phone call that just changed my life. It was my dad, and he said, David, I need you to come home tomorrow. Your mom has brain cancer. I was just like, What? What mom? Because she just was the most amazing person in the world. She had supported me through everything. I had just gone off to college and came home and learned that she had this horrible form of brain cancer where basically no one lives for more than a year or two. I was optimistic and hopeful that she was going to be the one that was going to live, battle this disease. She fought so hard, Sean. But over the course 15 months, the cancer recurred and it progressed. She ended up passing away October 2004. But during her battle, I saw her do so many things that, to your question, that ended up becoming so critical for me when I got into my battle. I mean, Sean, she had this horrible brain surgery where they actually opened up her skull during the surgery while they were taking out parts of the tumor and woke her up.

While While the skull was open, woke her up while they were cutting out pieces of it. It's this really intense, crazy surgery. They closed it up. She came out in the waiting area, and then they took her back. I remember my dad, my sisters and I going back to see her, and we were so nervous. Is my mom going to still be there? They just took out a bunch of her brain with this brain cancer. Is this going to be the same person that we've loved and just the most amazing person in the world? We get back and we see her, and she's got this wrap around her head and a bulb coming out of her skull. She looks at us and she pointed to her head and she said, Chiquita Banana lady. We just burst into laughter. She thought she looked like the Chiquita Banana lady, and we were like, Oh, my gosh. We've still got our mom here. She's still here. This is who we loved before. But it showed me that even in the midst of literally the worst surgery you could ever go through, she was thinking about us. She wanted to make a joke for us, which to me was just this incredible selfless act.

But she passed away, as I mentioned, 15 months after that surgery. Just before she passed away, I promised her I would dedicate my life to trying to find treatments for patients like her. I said, Mom, I'm going to be a doctor. I'm going to try to find drugs to help people just like you. She loved the idea. She had very limited speech towards the end of her life. The two words she could still say were unconditional love. She said unconditional love. I was like, All right, I got to do this. I decided to go into medicine. I was pretty mad. I went to Oxford for grad school, Penn for med school. I was on this on my way to fulfilling the promise to my mom.

You were 19 when that happened.

I was 19 when she passed away. That's right.

When I lived in Florida, I came home from a deployment when I was contracting for CIA, and I had a neighbor. Her name was Wendy. And beautiful woman, beautiful person, two twin boys that were graduating, getting ready to graduate high school. And she came and told me that she had brain cancer, and I was like, I didn't know what to think. I was like, Oh, you'll get through it. I went on a deployment, again, came home two or three months later. Man, she was a totally different person. That was the first time I realized how bad a brink... This is where my fear that I was just telling you about derives I remember watching her. She gained a tremendous amount of weight, lost all her hair, and it got so bad that you could go talk to her, and you knew that she could understand. It didn't look like she could understand what I was saying, but she couldn't formulate the words and get them out to me. You could just see tears building up in her eyes because it makes me sad right now because I just had a tremendous amount of respect for her.

Like I said, she was a beautiful person, and she fucking held on. I think her kids were juniors in high school, actually, at the time. It was like a week after they graduated high school, and they got their... They knew where they were going to go to school. She held on for that long, and I was just like, Holy shit, man, that stuff is nasty. It It is. I just wanted to share that. I think you were sharing that.

Wendy's kids went through to lose their mom at that age. It's heartbreaking. It's totally heartbreaking.

It's heartbreaking. It's also the amount of suffering that Wendy, your mom, people with brain cancer endure. To hold on, to have the courage and the drive and the will to hold on to know that her kids are going to be okay with her gone. It makes me choke up right now. But I mean, it's... Man, I just don't wish that on anybody.

It's the It was the worst. And that same feeling of not wishing on anyone. I mean, for me, there was just this something just clicked in me and just snapped, which was like, I'm going to dedicate my life to getting revenge against these things. Because brain cancer is one of the worst ones out there, but there are some other just horrible, horrible diseases. And it was like, this disease just took my mom, and I'm going to spend the rest of my life, however long I've got, getting as much revenge as I can on as many of these horrible diseases as I can.

You made that You promised to her?

I promised her.

What did you say?

She said that she was concerned about how it would be after she was gone. She was worried about me, and this is a couple of weeks before she passed. I said, Mom, I'm going to be okay. I'm going to dedicate the rest of my life to trying to find treatments for people like you, for patients like you, and I'm going to just do this until I help as many people as possible. I knew that meant I would want to go to medical school, but I still didn't really know exactly what that meant. I also told her that I would start a grief support group for kids in college that were dealing with grief and loss. I also didn't know what that was going to really entail, but now I just promised my mom these two things on her deathbed. Now, like I said, she responded by saying unconditional love. For me, it was like, All right, I got two things I got to do in this life. I got to support other college students that are coping with the death of a loved one. We named the group AMF. My mom's initials were... Her name was Ann-Maurice Fagan.

Her initials were AMF. We started this group that stood for alien mothers and fathers. It's been over 20 years. It actually still exists. It's now called actively moving forward. So I knew I had to do that. And then now I knew I also had to make sure that as long as I'm breathing, that I'm fighting to try to find treatments for people.

I recommend you for doing that. Let's move on with the journey here.

Yeah. So we get to, now I'm a third-year med student making progress towards this dream. Even had just finished an OB/GYN rotation. I helped to deliver babies into the world, which is like a A pinnacle experience in medical school. Then I started feeling more tired than I'd ever felt before. I mean, think about the hours you work, you know fatigue. This was a fatigue that I'd never felt before, even as a med student. I noticed these lumps and bumps in my neck. I noticed fluid in my ankles. I was really healthy. I was like, What's going on here? I don't know what's going on. Horrible abdominal pain. I took an exam in the hospital, and I was feeling so unwell that I basically stumbled down the hallway from where I took the exam to the emergency department, told them about my symptoms. They ran some blood work, and the doctor came back really rapidly. He looked at me and he said, David, your liver, your kidneys, and your bone marrow are shutting down. We have to hospitalize you right away. I'm like, Wait, what? Me? How fast did this come on? This was about two weeks of symptoms.

Two weeks? Within two weeks, I went from like, I was as healthy as you could be. A few months before that, I'd won a bench pressing contest in the state of Virginia. I was as healthy as you could possibly be. Then all of a sudden, just now in the ICU, or first hospitalized, within a couple of days, I was in the ICU. I had a retinal hemorrhage that made me temporarily blind in my left eye. It's visions back. I needed daily transfusions to keep me alive. I was on something called dialysis because my kidneys weren't working. And literally, I was actively dying. I mean, everything was shutting down. I was actively dying. And we didn't know what it was. The doctors are like, We don't know what this Maybe it's an autoimmune disease, maybe it's lymphoma, a form of cancer. But whatever it is, we got to figure this thing out really quickly because it was killing me. I got more and more sick, so sick that my doctors told my family that I wasn't going to survive. My family came into town. My best friends came to town. Like, literally, one by one, marched in.

We snock cried, we hugged. I said everything that I ever wanted to say to them. They said goodbye to me.

Holy shit.

This is when I was I was 25 years old and kept getting more and more sick. At a certain point, my family had a priest come in the room and read me my last rights because they were sure that I wasn't going to make it. Fortunately, Right around that time, they did something called a lymph node biopsy where they cut out my lymph nodes because they thought I had cancer of the lymph nodes called lymphoma. When the doctors looked at it, they said, We don't think this is lymphoma. We think it's something called idiopathic multi-centric Castleman disease, which I was a med student, and I'd still never even heard of it before. But basically, it's a disease where your immune system attacks your organs until you die. It just destroys you and kills you. But the only thing they knew to try was chemotherapy. They were like, Well, if your immune system is trying to kill you, maybe we'll try to kill the immune system with some chemo. And so they gave me chemo in this last-ditch effort right around the time I had my last rights read to me. It just kicked in just in time, and I survived that.

But then I would go on to have a bunch of relapses.

What's going through your head as a 25-year-old man knowing that you're being told that you have a terminal illness? I mean, you're saying goodbye to your family. You got a priest reading your last rights. I mean, how do you handle that? I think about this all the time, if it were to happen to me, because these things just say that they seem to be more and more... It's like every day I hear somebody else, my mom got diagnosed with cancer. My friend, my friend's It's like every day you hear somebody else is diagnosed with cancer.

That's right. Yeah, it was heartbreaking. I was devastated. I had this amazing girlfriend, Kaitlyn, that I wanted to have a life with. I'd made this promise to my mom, I was going to treat all these patients, and I was going to discover all these treatments I wasn't going to be able to follow through on. I just felt like there was just so much that I was never going to experience that I wanted to so badly. I didn't have any regrets about what I did in life, but I just had this feeling of regret about things I never would get to do or that I never got to do. I was just heartbroken. But I think that I ended up spending about six months in the hospital in critical condition. I think about some of the things that you've gone through as a soldier and just fighting one day at a time. I think that there's three things that helped me to get through those six months of survival. I'd love to hear if you've thought about these in the same way. But for me, it was like for the entire six months, I I kept thinking about what I wanted for my future, which I kept visualizing a family with Kaitlyn.

I kept visualizing me in the lab trying to find drugs for patients. I had to have this vision for what I was fighting for. That was the first thing. The second is that I had this amazing support group around me, my dad, my sisters, Kaitlyn. They were literally holding my hand, giving me strength. I could feel their strength from the way they were holding my hands, from their voices. That gave me strength. Then the third thing is that It really was this, it's this cliché of one step at a time or one breath at a time. But for me, it really was one breath at a time. If you told me at the beginning of the six months, David, you're going to suffer the most horrible pain for the next six months. Every breath you take is going to be horrible. I gained 100 pounds of fluid. You're just going to be in constant agony while your organs are being destroyed by your immune system. There's no way I could have been like, I can do this for six months. But I knew I could do it for an hour. Then like, all right, I can do it for an hour.

Maybe I can do it for two hours. Then those hours just started stacking up. All right, I did it for a day. I can keep doing this. As long as I've got my family around, I couldn't have done it if it was on my own, but as long as I've got them supporting me, I can do this. All of a sudden, they stacked up and then I made it through.

Did you ever come to acceptance?

Well, I don't know if I would say acceptance, but there was one point where I was ready to give up, where I started slowing down my breathing, and my family was around me. My sister Gina was holding my hand, and everyone was saying goodbye. I just had my last rights read to me, and it hurt so bad to take every breath. It was just like I was fighting. Then I started to slow down, and I was going to let go. I heard my sister Gina, and I can picture it, I can hear it. She said, Just breathe, Dave. Just breathe. I heard that. I was like, All right, I can do this. I can do another breath. I was like, I'm not going to give it. I'm not going to slow down. But in my mind, when I was slowing down my breathing and letting go. I was expecting that I was going to be letting go maybe a couple of days of life early. Maybe it's a day of suffering, basically, that I was going to be letting go. Like you said, Wendy, she was fighting. You can fight for survival. When you're at the end, you can keep fighting or you can let go.

I was going to let go. I was ready to let go. But when she said, Just breathe, Dave, just breathe, I was like, All right, I can do that. I'm going to keep doing a couple more breaths. Sean, if I'd let go then, I would have known that I would be here 15 years later sitting here with you. But I took that extra breath. I kept fighting. And then, thankfully, the chemotherapy kicked in, and I'm sitting here with you 15 years later.

Man. I mean...

Yeah, if she hadn't said, Just breathe, I just breathe, Dave, just breathe, I'm not here.

So it is. I often think about that. Like I said, when I was just talking about Wendy, maybe your mom. You know what I mean? I think that you can prolong.

You can, at the very end. Death.

How does that... From somebody that faced it five times, is it just letting go, and then you think it just happens?

That's right. You're fighting. You've got adrenaline. You're at cortisol. You're literally giving everything you've got to every breath. You're doing everything you can to stay conscious, to stay there, to keep going. Obviously, I only was prepared to go once, and I let go once, but quickly said, No, I'm going to keep fighting because of my sister. But yeah, so that was the first one. And then two near-death experiences happened the next few months in that six-month period. Where my doctors, again, were like, he's not going to make it. And then all the blood work, everything said I wasn't going to make it. But I got more chemo. By the end, they were giving me seven different chemotherapy drugs, the worst chemos they have at the highest possible dose, thinking, maybe we can stop this somehow. And thankfully, they would just get me by. But then when I relapsed again a year later and then relapsed again a year after that, again, both of those times, it wasn't like, this is maybe going to be it. It was like, this is it. You fought really hard, you made it. But for me, each time my doctors told me that I wasn't going to make it after that first one, I was like, Yeah, but you told me I was going to make it last.

I'm going to keep fighting. I got this amazing girlfriend, Kaitlyn. I want to get married to her. I don't care if I go shortly. Well, I didn't want to go shortly after I got married to her, but I wanted to get married to her. I wanted to have this family. I wanted to do these things. I think that there is a real ability to keep fighting. But of course, for me, the chemotherapy was necessary. It's not like I could have willed myself into doing this. It was that chemotherapy could get my diseases under control and I could keep fighting.

Did you think about what would happen after death?

I did. I said a lot of prayers, and I I spent so much of that time when I was on my deathbed, sad about the things that I was going to leave behind here, that I spent a lot less time forward-looking into what was going to happen afterwards. There was a lot more just sadness about what was behind me.

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You've been in battle and you've...

It was different for me. I fear it a lot more than I did back then. Back Then I figured I had thought that I had reached the pinnacle in my life. I was a Navy SEAL. I was CIA contractor. Where do I even go from here? Yeah, I could have gone maybe and tried out for development group, but I mean, it was pretty damn close to the pinnacle. And so I just always... If it got hairy, I always considered myself dead already. I just never really expected to come back from any of those deployments. But in relation to now, that was an easy thought. I had brothers and sisters and parents, but I didn't have kids, my wife, Nobody on my radar. All I was doing was that. I can't really relate, you know what I mean, to what you were going through. I didn't have a fiancé. My future was exactly what I was doing at that point in time, which was what I loved. If I'm going to go, this is a great way to go. But luckily, I made it through.

Glad you did.

But you, too. Let's move on.

I make it through that six-month period somehow, some way, and I got put on an experimental drug, a drug that was gone into clinical trials for my disease, my rare disease, this disease called Castlemans, with a thousand patients diagnosed a year in the US, super rare. We thought it was going to keep me in remission. I went back to med school. Kaitlyn moved down to Philly. We're living together, and I'm back on track. I'm still leading this grief support network called AMF, but I'm back on track. I'm going to find treatments for patients. I'm going to finish med school. I'm going to take care of patients. Then I started to relapse on that experimental drug. Sean, that was so hard mentally and emotionally to go through. This is the drug that's supposed to work. It's working for other patients with my disease, and it just wasn't. I relapsed right through. It ended up back in the ICU with all my organs shutting down. And mentally, to go through that, that was really, really tough. And my doctor explained to me, this is now for the fourth time, David, you're actively dying. It's unlikely you're going to survive this.

And the drug you were just on is the only drug that anyone is working on for your disease. There are no more leads. It's like, this is it. The drug you're on that you just relapsed on, this is it. There's nothing else. And I remember my dad and my sisters and Kaitlyn were around me, and I remember there was a minute or two of us just crying our eyes out. This is the world's expert. This doctor is in Little Rock, Arkansas. He's the world's expert for Castlemans. I'd gone to see him, just like we're talking about earlier, you go to the expert, and he's telling me, there's nothing else. This is it. We tried everything. He said, I'm going to give you the chemotherapy that you got in the past, all seven of those chemotherapy drugs. I'm going to give them the highest possible human dose we can give. Let's hope they work. But you're approaching the lifetime maximum of chemotherapy. This one drug called Atromycin, we're not going to be able to I'm going to keep giving you more, and this stuff is going to stop working. You just need me to be prepared for that.

We were balling our eyes out. Then when the doctor left the room, something clicked the same way that it clicked with my mom. That's when I told them that I'm going to dedicate the rest of my life, however long that is, trying to find a treatment for Castleman disease. I didn't know what that would be. Frankly, I didn't have a billion dollars in 10 years to create a new drug, which is about much time and money it cost if you want to make a brand new drug. I didn't have the money, I didn't have the time, but I had a really simple and important realization. That was those seven chemotherapies that I kept getting that kept barely saving my life. None None of them were made for Castleman's disease. They were all made for cancer of the lymph nodes for lymphoma, but they were saving my life from Castleman's. I was like, Well, wait a minute. You're telling me there's no more drugs for Castleman's disease, but you just use seven drugs for lymphoma, and those just saved my life. What if there's an eighth drug for lymphoma? What if there's a ninth drug for something else that could work for Castleman's?

My doctors were like, Well, but there's nothing else that we know of. I'm like, Yeah, but have we tried all 4,000 drugs for Castleman's disease? That became my just total locked-in focus. It was like, I can't develop a new drug from scratch. I want to get married to Kaitlyn and have a family. I want to develop drugs and treat patients. I got to find a drug that already exists for something else, and then I got to try it on me. That just my total focus.

Where did you start?

To start, I spent a lot of time just researching online, are there any case reports of doctors trying different things? It happened in Japan, there was a doctor that was trying these different drugs. Then when I relapsed and had my fifth deadly flare, I actually started trying those drugs that had been used in other parts of the world. I asked my doctors, Would you prescribe this drug? It had been used in Japan, and we tried it and it didn't work at all. I said, Well, can you try this other drug? It was used for a disease like Castleman's. That drug worked, but I just relapsed right through it. I ended up back in the ICU. I felt so disappointed because I had spent that year thinking about what could be tried, and we tried these two drugs. But the third thing I had done was that I started storing my blood samples every couple of weeks in the freezer at a lab at UPenn, because my belief was if I relapsed, and I thought I probably would, that I needed to get those blood samples so I could figure out what was going wrong so that I could target it.

I needed to get basically some evidence to figure out what to go after. Thankfully, I survived that fifth episode again, again with the seven chemotherapies. When I got out of the hospital, and actually even while I was still in the hospital, I turned to my sisters and to Kaitlyn, and it was like, Let's get all the samples we can, all those samples that are in freezers, the lymph nodes that are here and there, get them all to Philly. I'm basically going to go to the lab, and I'm not going to leave until I figure something out. Got back to Philly, and then I just worked basically day and night running experiments. I thaw those blood samples, measuring proteins in the blood, measuring what those immune cells were doing. I eventually identified that a communication line in the immune system, you've got all these immune cells all over your body, and they got to communicate with one another. I discovered that one of those communication lines was turned into overdrive. To me, I thought of it as like, it seems like maybe the fire alarm is going off in my immune system, even when it shouldn't.

It's like a false alarm. Therefore, it's attacking everything. What was really important about that discovery, Sean, is that there's a drug that's been around for decades that can turn that communication line off. It was made for organ transplantation. If you were to get a kidney, your immune system would attack that new kidney, that transplanted kidney. Unless you took this medicine, which would prevent your immune system from attacking that transplanted kidney. That drug turns this one communication line off. I went to my doctor, a doctor in DC, and I was like, Hey, would you consider prescribing this? He's like, Well, it's never been done before for Castlemans. It could cause problems. It could turn things He's in the wrong direction with your immune system. Maybe this could kill you. I said, Well, but I've already died. You're already dying. I've almost died five times, and I'm out of options. And so he prescribed it. And so I started taking it. And it's, Sean, it's now been over eleven and a half years. I've been doing great on this drug. No relapses, just full remission.

Wow. Do you still have to take the drug?

I take it every day. I took my three pills this morning. And the moment that these drugs, or these three pills, started working for me, Sean, I immediately I have gone into this just total focus and obsession like, holy shit, how many other drugs are made for other diseases that could treat more diseases? This drug wasn't made for me, and it's saving my life. Are there other drugs that are out there that could treat more diseases? And are there people suffering today that could actually benefit from a drug that's already sitting in their CVS? Because I shouldn't be here. I'm alive thanks to this medicine that I discovered. But if I had died at any point in those previous three and a half years, we wouldn't know that serialimes could treat calcimines. There's thousands of people around the world that are benefiting from this drug, and it's like, no one would have figured it out. How many more of these hidden cures are just sitting there?

Did you talk to the doctor in Arkansas about this? What was that conversation like?

Yeah, I talked to him about it. He's incredible, and I still work closely with him. Yeah, he basically said, Look, David, it's never been tried before. It's probably not going to work. But there's probably not too much downside or to your point, even if there is a downside, I'm already going to die from this disease, so we should at least give it a shot. But there was no data. It hadn't been used in a human before with Castleman. So I can understand the hesitancy because it could have turned things even worse. But it also was my last-ditch effort to try to stay around.

What did he say afterwards?

When it worked? It was a test of time because I started feeling better. My blood results started getting better. It was clearly working early on, but I'd gotten better multiple times before, and then it came back within a year. I wasn't willing to get too excited. I just was like, All right, it's going to be a test of time. Cautiously optimistic. I started taking it in January of 2014, and Kaitlyn and I, our wedding day was May 24th, 2014. It was like, Am I going to make it to May 24th? It was this countdown. We made it to May 24th. My hair grew back just in time for wedding day because all the chemo. It came back just in time, and Wedding day, you're like, My hair's back. I made it to May 24th, 2014. We had the most amazing... Every wedding is amazing. This wedding was extra special because everyone that was in attendance was like, I can't believe this is happening. I couldn't believe it was happening. Then, of course, when you think about saying, till death do us part, it has a whole different meaning when you know that the person you're marrying, for me, Kaitlyn, she was there with me through everything.

You We had a little conversation before the interview about how you guys were engaged, and you had a question for her. Could we revisit that? Absolutely. What an amazing woman.

She's incredible, isn't she? Just with me through everything. The question I had for her was, right when I finished those six months in the hospital, Sean, you've seen the picture of me. My head's bald from chemo. I've got this huge belly because of my liver and my kidneys weren't working. Actually, I'll tell a story about that in a minute. Caitlin came down to visit me in North Carolina. That's where I've been hospitalized. We're sitting on this couch in my sister's house, and I got my hand over my head. I remember just been like, Caitlin, I've got a terminal illness, and are you sure you want to be with me? You could find so many amazing people. You're amazing. Are you sure you want to be with me? I'm going to be sick, and I don't know how much longer I have. I remember she looked at me and she looked offended. I was like, Wait, what? She was like, Of course I do. Why would you even question that? Absolutely, I want to be with you. Then when I was saying to you, I was joking about it. I was like, Once you said that, I was like, I'm not going to ask you anymore.

I'm going to take that. You've said it. I've warned you, and you said you want to stick around with me. I never asked again. She's just been amazing. She's just by my side. But I got to tell you the story from just before that conversation, right before I was, or about two months before I was discharged from the hospital, it was New Year's Eve, 2010. I just got in chemo. I just finally well enough to walk around the hospital. My dad and I decided to do a walk on December 31st, New Year's Eve night, about 8: 00 PM. I've got this huge belly, my head's bald from chemo. I've got my infusion that I'm rolling with. We passed by the family waiting area on the on the cancer floor, and there's a guy who's visibly drunk. He's swaying in his chair on this unit. We come by the next time, and he's fallen onto the ground. My dad runs over to him and helps him back into his chair. He looks at my dad and I, and he says, Thanks so much. Good luck to you and your wife. We're like, Wife, what is he talking about?

Then I looked down on my belly and I realized he thinks that I'm my dad's pregnant wife and that we are walking laps to deliver our baby on New Year's Eve. I turned to my dad and go, Man, I go, You got an ugly wife. We just die laughing. But that's what I looked like, Sean, when Kaitlyn was offended that I was like, Are you sure you want to be with me? That tells you how committed she was to me. Wow, that's amazing.

Is she a medical professional, too?

She's not. She used to work in the fashion industry, and now she's full-time with our kids. She also helps a lot with Castleman's and every cure and raising awareness.

What was the drug that cured you?

The drug's called Cireliumacetam. The other name for it is Rappamycin. That's a drug that maybe some of your listeners will be familiar with. Rappamycin is an MTOR inhibitor, and actually, it's thought to have some anti-aging properties. Sometimes people take low doses of Cyrilimus or Rappamycin. I take a really high dose. My dose destroys my immune system.

Damn. Have other people with calcium has been treated since then?

Yeah. So once it started helping me, and once the months and the years started going by, right around the time, actually, I joined the faculty, the University of Pennsylvania, to build a center to do more of this, basically to study the immune system, to figure out are there drugs that already exist that you could repurpose? That became my life's mission. I started that at Penn, and then we started treating Castleman's patients with this medicine. It actually worked for the first three patients that we treated. I was like, Oh, my gosh, maybe we figure it out. Maybe this is going to work for everyone. It turns out that it works for about a quarter of patients, and so there's still more work to be done. But yeah, the first patient that I saw that we treated was this young boy named Joey, who was in the Children's Hospital, Philadelphia. I'll never forget seeing him just before treatment started and then seeing him a couple of days later and seeing the blood work and seeing that things were improving. Days and days. Within days. He was critically ill in the hospital. Within days, seeing things were starting to stabilize and they started getting better.

I would come by every day, and his mom would hand me the lab test, and I would look at it, and I was like, Oh, my gosh, Joey, this is working. For me, that meant so much. He's now a sophomore in I was at Temple University in Philadelphia. I just saw Joey a couple of weeks ago. I'm like, he wouldn't be here if not for this drug that I came across that saved me. And now we've got patients all over the world on it. It just means everything.

If it works 25 % of the time. I mean, a thousand people a year in the US, you said they'd have this 250 that are going to go on to do great things. Yeah, exactly. I mean, how does that feel to you?

It's incredible. The feeling, and actually, the thing that's most incredible, Sean, and I don't know if you'd immediately appreciate this, but for me, what I found is the most incredible part is when I got to hear about what these people are doing, basically in this over the time that they've got. Joey's a sophomore in college. Kyla, who we repurposed another drug to save her life, she's now trained to become a nurse. She wants to take care of people with illnesses. Like nurses took care of her. Michael, who has a rare cancer, we repurposed a drug for his cancer. He walked his son down the aisle a year ago, eight years after he was diagnosed with this terminal cancer. Then just last weekend, here in Nashville, he walked his daughter down the aisle. When I get to see those pictures, when I got to hear about those things that they wouldn't have done, for me, it's one thing to be like, Oh, months or years, but it's like, Oh, I got to walk my daughter down the aisle nine years after I was diagnosed with a terminal cancer. That's just the most incredible thing for me.

Man, that has to feel amazing.

It's incredible. It's really drive you to want to keep doing it because it's an experience when you hear about any one of these things where you're like, I just want to do this for more people. It's this combination of when you can help people like that, that means so much. Of course, in my case, every day I breathe, I can remember what it was like. But the other thing is that there's also all suffering happening right now in the world. There's people, as you mentioned, getting diagnosed with this disease and that disease. Every day, Sean, I'm hearing from a patient with a horrible condition or many of them. You juxtapose all of the incredible hope that you get from all the people you can help. Then all of the people who are suffering right now from horrible diseases. That's just true enough to say, we've got to make sure that all the drugs that we've got, there's about 4,000 drugs that are FDA approved. We got to make sure every one of them is used for every disease they can possibly treat. So that way, these people suffering over here, if there's a drug for them, we got to get it to them.

And it's not that I believe, Sean, that every patient with every disease could be treated with an existing drug. I don't believe that's the case. But I do believe that if there's a drug that could treat some of them or a fraction of them that's already in our CVS, we got to find it.

Yeah. I don't know how often this happens, but just two examples off the top of my head. I mean, Viagra was originally a blood pressure medicine, correct? Exactly. Now People are getting busy in their 80s, and hopefully, I'll be one of them. And then the other one that comes to mind is, and I've never used it, but Ivermectin with COVID. A lot of people, Joe Rogan, swears by Ivermectin to fight COVID-19. How many other of these drugs are there?

There are a lot of drugs that can be used in multiple ways. Viagra is a funny one because not only, as you mentioned, it from heart disease to erectile dysfunction, but it actually is also used for this rare pediatric lung disease called pulmonary or tiller hypertension. Kids were dying because they weren't getting enough blood flow in their lungs. A random doctor thought to themselves, If this can increase blood flow for these older men, could it maybe increase blood flow to the lungs of these little kids? Then it was tried and it worked. For me, those sorts of examples were like, you would never think of pulmonary retinal hypertension in little kids as being similar at all to a rectal dysfunction. It's because even though the conditions appear very different, they share the same underlying problem, which is limited blood flow. There's a lot of examples in medicine, and there's another drug you've probably heard of called thalidomide. It caused all these horrible birth effects back in the '50s. That drug can treat leprosy and also this blood cancer called myeloma. Leprosy and myeloma, again, they seem so different, but they share the same underlying problem.

It turns out that just like you said, There are drugs that can do one thing in the body that can actually have an effect across multiple diseases. Typically, this is discovered through random chance. This doctor I mentioned in Houston who was like, I wonder if Viagra could be useful for these kids. It happened randomly, and there isn't a system that exists. There's never been an entity, whether it's in the government or within the industry, that's just been focused on saying, Okay, among the 4,000 drugs that are approved, that are available, what are all the other diseases they can treat? Because it hasn't done systematically, I could discover a drug like Cireliums could save my life. Drugs can be found, like tocilizumab could be used in all these different ways. There's all these drugs out there, and there's just never been an entity to say, We're going to match in everything we can.

How many drugs have you personally found the treat?

We've advanced 14 drugs, 14 for diseases they weren't intended for.

Fourteen drugs?

Yeah, 14. Is that incredible? That's in the last just 11 years since serolimus, of course, being one of them. That's primarily from my lab at Penn, where we're focused on just a few rare cancers and inflammatory diseases. About three years ago, I'm sitting here thinking, Okay, In our small lab at UPenn, we're advancing. At that stage, it had been over 10 drugs for diseases they weren't intended for. It's like, how many more are there out there? What was so important that this came up about three or four years ago is that one of my really close friends from medical school, Grant Mitchell, was really pioneering the use of artificial intelligence to use medical record data to try to figure out subtypes of patients that could benefit from one drug or another drug. We came together and we said, what if we could utilize artificial intelligence to scan across every drug and every disease? My lab works on a few diseases and a few drugs. What if we could actually scale what we're doing for these few, but to all? What if we could use AI to look across all the world's knowledge to come up with how likely every drug, all 4,000 of them, or to treat every disease, all 18,000 diseases.

If AI can help us to figure out what looks most promising, then we can do the hard work afterwards. We can work in the lab, we can do the clinical trials, we can do what's needed to prove it. But let's actually start by using AI to make these matches. Grant and I co-founded a nonprofit called EveryCure, along with Tracey Sokora, our other co-founder, which is on this mission, which is to save and improve lives with the drugs we already have. We start out by using AI to scan everything, the world's knowledge of everything versus everything, to find out the very best opportunities to take forward.

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There's 4,000.

4,000 drugs. I mean, There's a lot of conspiracies around pharmaceutical industry, and that they don't want to cure cancer, and they don't want to cure these drugs. They just want to prolong. Basically, what I'm getting at is they just want to make money. They don't really give a shit about people's lives. I don't know if that's true or not. A lot of conspiracies running wild in the world today. But one question I have is, when you find a drug like this, especially the one that you were just talking about that was a sleeper back that they were using it in the '50s. It was crazy.

It's a little bit of my idea.

It was crazy. Birth defects. I don't know what company developed that, but when you're taking a drug that's a Pfizer drug or whatever, are these companies helping you do the research? Are they funding it? Because they stand to make a lot of money if you repurpose the drug and you do the research, correct?

It's a great question. It ends up that it's so much more complicated than it should be. And the reason it's complicated, and it should be, and the reason it's complicated, it's is that once a drug gets approved for one disease, it has about an 8-12 year lifetime before it goes off pad and it becomes generic. Basically, drug companies, when they develop a drug for one disease or a couple of diseases, they've got an 8-12 year clock before it becomes generic. Once it becomes generic, then anyone can make a copy of that exact same drug. There might be 10 people making the same drug, and the price plummets because it's all the identical drug. So drug companies stop making money once their drug becomes generic. They have to I think in those 8-12 years, what are the diseases that are most profitable? They tend to go after the most severe diseases because the most severe are the most common diseases because that's typically where they're going to be able to charge the most amount of money. So how common is it and how severe is it? That's usually where they go. But they can't typically go after a lot of different diseases because they want to really focus on maximizing profit for the few they can.

It's not that they're avoiding diseases. Again, this is partly my opinion, but I'm saying it as someone who lost my mom to cancer and who personally has battled these horrible diseases. If I was seeing things like people hiding cures, I'd be the first person to talk about it. I don't see that. What I see is that drug companies focus their drugs on whatever diseases they can make the most money on in those 8-12 years because they're businesses. The moment that drug goes off pad, then all research stops. What that means is that we've got 4,000 drugs. Well, 80% of them are already generic. There's no drug company that has any interest at all in selling more doses of that drug because there's 10 manufacturers, and they all sell them for a penny a pill. The problem is that, in my opinion, the problem is not that drug companies are not pursuing these additional uses. The problem is that if I discover that ruxalidineb can be useful for a new condition after ruxalidnib goes off patent, I got to figure out a way to drive forward the science for it. I got to figure out a way to get, whether it's the government philanthropists or individuals to donate to do the research because the drug company is like, Hey, I made it a few years ago, but 10 other people are making it right now, and I don't make any money off of that drug.

I'm on to another drug now. And so I think that that's a problem in our system is that 80% of our drugs are not profitable to find new uses for them. So that means someone's got to stand up and do the work, right? It's like whether it's the government or some entity. And so that's where we at Everycure said, We figured someone else was doing it. When I got in this, I'm like, There's got to someone who's doing it. It's like, oh, wow, there's no one who's picking these things up once they're generic and finding more uses for them because no one's incentivized to do it. So we've taken that up.

How do you fix this at scale? I have a feeling you're going I don't say AI, but I mean, and maybe that is the answer. Is there a better answer? I'm just curious. Let's say the US government gets involved, and they start to incentivize the drug companies to They continue their research, maybe they grant the patent for another 10 years, or maybe they subsidize it. What is your answer?

I think what you just described, I think that's the only way you can do it, is that if you want to do this fully at scale, I think what you have to do is you have to incentivize these companies to say, Yeah, you get more patent life, or maybe your drug that's off patent, you can get a patent back on it. The thing is, is that if you do that, you're going to end up saving a lot of lives because that's going to drive a lot of cures. You're also going to increase the cost of health care because those cheap drugs that are generic, it's good for the health care system for them to be cheap. That means that they go from being thousands of dollars or tens of thousands of dollars a dose to tens of dollars or hundreds of dollars a dose. That's good for cost of our health care system. It's going to increase costs, it's going to increase cures. That's where the challenge is, is that if you incentivize that, you're going to increase pharmaceutical costs. Now, I would make a pretty strong argument that even though you're to pay more for drugs, you're going to end up saving the healthcare system in the long run because people are going to spend less time in the hospital.

They're going to have less other issues, less comorbidities because you're going to be treating the actual diseases and they're not with the drugs we already have. It ends up becoming probably, I think, close to a wash or a cost saver. What I think is needed is for the federal government to also just rather... One is you can incentivize the drug company to do it, or you can just spend on proving these things work and use the cheap version of it, use the drug that's already out there. That's basically what we're doing right now. At Everycure, we actually have a federal contract with a US agency called ARPAH, where they are actually funding a lot of the work that we're doing. We're finding new uses for medicines that will end up saving money to the healthcare system without actually creating these incentives that maybe aren't aligned.

How big is your team?

We're about 50 people. 50 people?

Yeah. Is that enough?

I think that when you think about the world we're in, which is we got 4,000 FDA-approved drugs, and they're approved for about 4,000 diseases, but there's 14,000 more diseases that don't have any approved drugs. That's a crazy stat, right, Sean? A lot of those 14,000 are very rare diseases, but collectively, we're talking tens of millions of people have these 14,000 diseases with no treatments. And so there's a huge opportunity to match these 4,000 drugs to these 14,000 diseases that, yeah, a 15-member team is not going to be able to do. So I think that at At some point, we're going to need an effort, whether it's ours or in others, that's as big as the Pfizer's and the Merck's of the world that are doing the nonprofit drug development. We joke that every cure, it's a nonprofit drug company, basically. We're just looking for the nonprofit stuff to help people. We don't care what the drug was made for. We don't care how common the disease is. We just want to relieve suffering with the drugs we already have. But we joke that we're both the biggest drug company of all time because we'll use any drug out there that can help people.

But we're also the smallest drug company because we don't own any drugs. We're just using the things that are already out there. But I think that proving out the impact of what we're doing and using AI to focus us in on the right opportunities, I think is important. Then as we help more and more people, I hope that that will lead to more support, whether it's from individuals who care about someone with a horrible disease or whether it's philanthropists or the federal government. I hope it's going to lead to more opportunities here because like I said earlier, I'm alive because of a drug that wasn't made for my disease. There's a lot of people suffering today that could benefit from a drug we already have.

It's government funding in conjunction with donations. That's right. Philanthropy as well. Where do people donate?

You can go to everycredit org/donate, and you can donate along. We're a nonprofit organization, and we put every one of these dollars towards making sure that the drugs we have help the people who can benefit.

Man, that's amazing. Thank you. I'm donating. I love it. Thank you. Donate. I love what you're doing. Thank you. Let's talk about some of the other successes that you've Sure.

I shared a little bit about... Maybe I'll share a couple of these patients. One of them is Michael. He was diagnosed with a horrible form of cancer called metastatic angiosarcoma. That's where basically this cancer is in multiple places in your body, and no one lives past a year with metastatic angiosarcoma. This is 2016, and we found a study from 2013. It was just a laboratory study. It wasn't It was done in patients in clinical trials by any means. It was a lab study. But in that lab study from 2013, it indicated that this one marker was up called PDL1 in a few people's tumors from angiosarcoma patients. What was important about that is that there's a drug that's really good at inhibiting PD-1 that already existed for other cancers. It was approved for melanoma at the time and also approved for lung cancer. We saw that result in this paper and thought, Well, maybe his tumor also has increased PD-L1, and maybe that drug could work for it. It had never been used before for his form of cancer. But he was told by his doctor that they were out of options, that there was nothing else that could be done.

The chemo that they had tried wasn't working. We actually ended up getting that test done, and it came back that it was very positive for the thing that we thought it would be from that paper. We were able to get Michael on this drug called Pemberlizumab as the first patient ever with angiosarcoma. As I mentioned, a year ago, he walked his son down the aisle on his wedding day eight years later. Just last weekend, here in Nashville, last weekend, he walked his daughter down the aisle on her wedding day. This drug was always there. No one had ever tried it before. What's important is that this drug is also now used for other patients, the Angio-sarcoma. Unfortunately, it only works in the numbers, about 18% of patients. When it worked for Michael, we're like, Oh, my gosh, we saw Angesarcoma, got so excited. It doesn't turn out that it works for everyone. But for those 18% of patients, it's everything, right? If it works for you, it is a life-changer.

Maybe if it's just one life. Exactly. It's a success in my opinion.

Because the drug was already there. It's not like you had to create a new drug. It's already there. You just had to give it to someone. That, to me, means the world. That was the first time that we went into a disease outside of Castleman's or related to Castleman's. It was the first time. It was like, Oh, my gosh, we can do this outside of the diseases that we're focused on, which was so important for us to want to keep pushing this mission forward. Another one is a young girl named Kyla who has Castleman. She has the same subtype of Castleman as me, the really deadly one. She spent about a year in the hospital. Nothing was working at Chicago, Loury Children's Hospital, and nothing was working. One day, her doctor called me late. I remember during the pandemic, it was 8: 00 PM one night, and said, We've been trying things for a year. Nothing's working. The drug that I'm on, Cirelimus, didn't work. Chemotherapy wasn't even working for her. Is there anything you can try? Just a couple of weeks before, a couple of members of my lab had discovered that this one part of the immune system was in overdrive, not MTOR, but something called JAK.

I recommendable. It's early days, but you could try a JAK inhibitor in Kyla. We've shown this stuff in the lab. Maybe it'll work. Kyla became the first patient ever with Castleman's to be treated with a JAK inhibitor. She responded so Well, Sean, and she is doing so well today. I mentioned she's training to become a nurse now. It's just incredible that this drug was always there. We actually have just opened up a clinical trial of that drug. We're going to study it in more Castleman's patients because when you do these They're called N of ones, where you try a drug off label in one patient and it works. That's great. But you really want to get more data to prove that it works. That way you can get more patients on and you can really figure out who's it going to work for. So we have a trial, but we just opened up for that.

How How many test subjects do you need for a successful trial?

It's a great question. So it really depends on a couple of things. The more effective the drug is, the fewer test subjects you need in the trial. Because if it's clearly effective, you could have a trial of just 20 people, but if the 10 people that got the drug all do better and survive, and the 10 people don't get the drug, none of them survive, that's night and day. So one part is how effective is it? What's the effect size? And the other one is how common is the disease? Because really rare disease, sometimes you're forced to have very small numbers. But if it's a common disease, the bigger, the better in terms of how confident you are in the result.

When you repurpose these drugs, how does the word get disseminated across the world, across the country and the world, on how to cure these disease? You know what I mean? I mean, for the everyday, I guess I shouldn't say everyday professional because I'm sure they're very specific, trained doctors for that specific disease. But I mean, how does the word... How do you get that out?

How does it happen? This is so important. I mean, honestly, right now, it happens very randomly and sporadically. You publish a paper in a journal and you hope a doctor reads that journal, or you give a talk at a conference and hope the doctors are there. It's very sporadic, but we're trying to fix that with every cure. I'll share an example that is actually also got a Nashville connection. An amazing doctor named Chip Chambers had two kids born with a rare condition called DATA-2 syndrome. Data-2 causes kids to start having strokes at very young ages, and they usually pass away in their teenage years because they've had hundreds of strokes. It's horrible. About 15, almost 20 years ago, a doctor randomly tried a drug in one of his patients with DATA, too, because he thought the patient's profile looked similar to another disease. He was like, Oh, I'll try this drug that I use in this disease for this one because nothing's working for these kids. It worked really well for that first kid. That kid stopped having strokes. The doctor gave it to a few more of his kids with this condition, and he helped.

He was great with the patients he took care of, but the word never spread. Then Chip Chambers comes around. He has two kids with DATA 2. He learns about this doctor who's doing that. He's like, Oh, my God, this is amazing. I'm going to get my kids on it. Chip starts a foundation called the DATA 2 Foundation. He starts reaching out to every doctor around the world. He's sending emails, he's tweeting. Now everyone... Well, another important step, we He published a paper with guidelines. Okay, this is how you treat data, too. It's out there for the world. Then he started telling everyone he could. Now every kid in the world that's diagnosed with data, too, they get this drug, they stop having strokes, and they live full lives. But there were a lot of years between that first doctor doing it. And he did his job. He was helping his patients. He was brilliant to think of that. But to your point, you got to disseminate it. You can't just treat your patients. But the thing is, it's not a doctor's job to be a PR marketing for how to treat patients. Their job, take care of their patients.

He did a brilliant job. But that's where I think every cure has to come in. And honestly, that's why being on a podcast with you like this, I think is so important. Because when we find these drugs, we got to get the word out to people. And being able to work with people like you and others to get it out is literally a tweet. Social media post can be the difference between life and death for someone.

Man, I mean, isn't there some type of... I mean, like I said, I have no insight into the healthcare industry other than through the podcast. Isn't there some a database that all physicians use and they can type in a specific disease or treatment for anything. And it's these drugs right here. These are what we do.

The closest to that is a website called UpToDate. And the idea is that the world's expert for every disease enters that in and keeps up to date. That's why it's called UpToDate. So that's the theoretical place. However, sometimes when you use a drug, they were using data, too, for that rare condition or using that TNF for data, too. If it's just happening in one part of the country or one part of the world, it may not get into that database for up to date. It may be that there's debate, okay, well, it's only been using a couple of people. Like, are we sure there hasn't been a trial done yet? And so it's not perfect. Up to date is a really good place. It's not perfect. And then the other issue is that it's updated by individual experts, and so they might miss things that are here or there. And it's also not widely available. Not everyone has access to up to date. And so we at every cure feel that we got to make sure that up to date pages are up to date, and we also got to make sure that we get the word out to people that don't have access to it.

Damn, I wish there was a better way than that.

I know, right?

I wish there was a better way. I mean, that would jet launch it.

We would. And that's what we're hoping to do with every care. I'd love any ideas you have for how to get it out. I mean, that's all we care about. It's like the drugs we got should treat all the patients who could benefit from the drugs. And it's like, we got to just figure out how to make that match.

More podcasts. It's a small podcast. It'd be great if the media, the mainstream, would jump on this, and it would be great if they had the database. It sounds like they do, but it just seems like there should be something that the world can tap into, and it lists out every possible drug and scenario that they can read. I totally agree. How does that not exist?

It's the thing that we all think someone must have done, or there must be something like that. And then you You sit around, and then all of a sudden you realize, if no one else is going to do it, I guess we have to do it. I guess somehow these things just... Everyone's got their lane, right? And it's like, oftentimes we lose track, and there isn't someone who's taking that big picture look.

Man, Man, let's move into the AI stuff. Sure. You're utilizing AI to basically do the initial research. That's right. How do you do that?

Sure. We use something called a biomechanical knowledge graph, which is basically like if you took every drug, disease, gene, protein, everything you can imagine that's related to medicine and bioscience, and just put it on the wall, like mapped it up, and then you put connections between every one of those things. We know that interleukin 6 is elevated in Castleman disease, and you'd put that onto your map. You'd map every single concept, and then the relationship between everyone. You'd create a map that basically represents what we know about all of medicine, like every drug, every disease, every gene, every relationship between all of them. Now you've got It's a map of what we know about all of medicine. Then we train machine learning algorithms on treatments that we know work. We say, sultuximab treats Castleman disease. Cyrulimus is effective for organ transplant rejection. We train the algorithm over and over again on all the known treatments. It gets really good at picking up the pattern of connections. Okay, if that drug treats that disease and that drug treats that disease. Then we say, okay, now that you know what a good treatment looks like in this map of knowledge, now give me a score from zero to one for how likely every other drug is to treat every other disease.

There's 4,000 drugs, there's 18,000 diseases. We're basically asking it to calculate 75 million times the 4,000 drugs against 18,000 diseases, 75 million times how likely every drug is to treat every disease. It's between zero and one. Then our medical team, we look at the things at the very top. Say, what are the 0. 99s? What's machine learning, artificial intelligence saying is the highest, most likely drug to treat a disease? That's where we start.

Wow. So it sifts through everything.

It sifts through everything. It goes through the world's knowledge. Actually, when we were here for the first time, Sean, we built the nonprofit three years ago, spent a lot of our first year fundraising, but we finally hired our first data scientist. We finally ran the algorithm for the first time about two and a half years ago, and it took 100 days to run the algorithm, to literally scan everything the world knows about everything, 100 days. We didn't know it would take 100 days, but just every day, it's slow. We don't have the results back. Finally, the result is 100 days. Sean, now it takes 17 hours to scan the world's knowledge of everything to get a score, 75 million scores in 17 hours, which the reason that's really important is because then you can actually improve the algorithm and say, That's actually not the way to do it. We want to do it more like this. You run experiments and see what's the best way to get the best results. And if it's a 17-hour turnaround time, you can just keep doing it.

Wow. I mean, would it be a possibility that that AI database could be the answer to what we were just talking about?

I think so. A part of it could be. So when we score every drug against every disease, in that database, you now would have a bunch of drugs for diseases that score poorly or that are middle-level. And so There's parts of it that maybe would be not that helpful, but the things at the top, absolutely. The things at the top very much can be... At the very top, let's say for a horrible disease, let's say, ALS, there's two drugs that are FDA-approved for ALS. They don't work very well, but there are There are drugs that are FDA-approved. That's got to be at the very top of the list. Then right below those two FDA-approved drugs, there are some drugs that are sometimes tried where there's early data. That should be next in the list. Then you should get into these AI predictions of, well, what's AI telling us? But what I wouldn't want is for people to skip the things at the top where there's good data and just go to what AI is predicting. Because for us, at every cure, when we make these predictions, we look at the things at the very top, but we don't automatically say whatever score is number one, we're going to give to patients.

It's like, whatever score is number one, we're going to look really deeply into it. We're going to study in the lab, we're going to do clinical trials, and we're going to figure out, is it the right thing for patients? But not necessarily. We don't trust fully in AI. It's basically what I'm saying. It's like AI for us is a great starting point, but there's still more work to be done.

Got you. Let's take a quick break. Sure. When we come back, I want to talk about some of the diseases that you're targeting nowadays.

Sounds great.

All right, Dave, we're back from the break. We're talking about all these horrific rare diseases, some of them not so rare. I mean, are you looking at any preventatives specifically for cancer?

Yeah. There's one of our programs. We've got six active programs at every cure, so different drugs that we're repurposing for diseases. One of them is around the numbing medicine, lidocaine. When you go to the dentist, you get an injection of lidocaine. The role that it can play in preventing recurrence of breast cancer. Actually, if you inject lidocaine around a breast cancer tumor, there's a really compelling evidence from a big clinical trial that was done in India that you're going to reduce recurrence of breast cancer and also reduce mortality from breast cancer. Now, this is an example where it's not total prevention because it's not like it's preventing the breast cancer in the first place, but it's preventing the breast cancer from coming back, which, of course, is so important because that's oftentimes what's so deadly about breast cancer. It's an example where lidocaine is this really cheap old substance where unless a nonprofit like ours or another nonprofit comes in, the work is just not going to be done to push it forward. We're really optimistic about that. We're actually also studying the role that lidocaine might play in other cancers as well.

Are you studying or do you have any Any insight on what causes cancer?

Yeah. The breakthroughs over the last 10 or 15 years really indicate that cancer occurs when mutations occur in the genomes of those specific cells. They're called somatic mutations. Basically, it means we're all born with our own genetic makeup, but within the cells, let's say in your pancreas, a mutation occurs. That could be because of exposure to UV light, or it could be from exposure to carcinogens in the environment, what you eat. Those genetic changes, if they happen in a part of the genome that isn't that important, that cell just dies and you never even knew the mutation happened. But if that mutation happens to happen in a part of the genome that's important for, say, cells to replicate or maybe to grow blood vessels, then that cell now has an advantage, and then it accumulates more mutations, and all of a sudden you have cancer. It's this It's this random set of things that have to happen for you then to develop cancer. Of course, you can do things in your life to reduce your risk of cancer by eating well and exercise and doing all the right stuff because that's going to reduce the amount of those somatic mutations that occur to your cells.

But it is this very much random thing, which is tough because that's why sometimes young kids get horrible cancers. It's also why you see cancers emerging in older years because basically more of these mutations have occurred over the course of life.

I mean, is there anything, too? I've heard a lot that inflammation can cause cancer, sugar can cause cancer. I mean, is there anything to that?

Yeah, so the inflammation, for sure, the more you proliferate, the more your cells are proliferating, which often occurs in the setting of inflammation, the more chances there are for genetic mistakes and basically mutations to occur because of the increased proliferation. So absolutely. Sugar, I think there's a lot of data that sugar plays a really important role in cancer development and progression. Like once it starts. I haven't seen as much on it, causing it to start in the first place. But it's also really hard to keep track of all the research because there's just so much work being done.

And then I've also heard that a lot of these diseases, and I might rattle a couple off that this is not true about, but cancer, Alzheimer's, a lot of these. I've read things and interviewed people that said, none of these are actually organic diseases. They are potentially a product of our filthy environment. Is there truth to that?

I think that our filthy environment contributes and probably increases risk and increase the numbers. I think all the conditions you mentioned have happened as long as we've been around. They're in textbooks from the 1700s, but they maybe weren't as common. One reason why they might not be as common, I think, is exactly what you said, there's things in our environment that are making them more common. The other is that we're, thankfully, living a lot longer. We're not dying from infections from bacteria that's in our water, for example. So we're living longer, which means there's more opportunity for these other diseases to emerge. I think that my experience with a lot of these things is that I think that there is definitely a lot of truth and data backing up the idea that our environment is playing a really important role in increasing the number of these cancers and conditions. But oftentimes, it's a lot more complicated than just like, it's just the environment, because these things have been in textbooks for a lot longer than a lot of these chemicals have even been around.

In another thing, I mean, there's a lot of ever since COVID, It's really caught fire after COVID. I mean, there's a lot of hesitation with vaccines. There's a lot of hesitation to pharmaceuticals. And there's this massive movement on, I don't know, holistic sick type medicine. What are your thoughts on that? I think it could be... I don't know. I don't really know much in this sector. My fear is that we demonize all of the progress that we've made with medicine due to conspiratorial claims. And so I'm just curious. I think there's got to be a healthy balance here.

There has to be. Yeah. My My feeling is that I and we just want to help patients with the medicines that are available. If it's from a holistic doctor or if it's from traditional Western medicine or if it's from pharmaceutical companies, the drug that I'm on, Cyrilimus, it actually was discovered in the soil on the island of Rapa Nui in the Pacific. It literally was discovered in the soil, and then a drug company figured out ways to manufacture it. My drug is about as natural of a drug you could ever take. But it's a pharmaceutical drug, and it's used for transplant rejection, and it destroys your immune system. We like to oftentimes think of things as very black and white. There's the natural stuff, then there's the pharmaceutical stuff. Well, my pharmaceutical stuff was natural. We just figured out how to make the exact same thing over and over again. It's a lot grayer than I think that it's easy to wrap our heads around. I think that we've just got to follow the data. What are the drugs that can help people? Is there data to suggest that it can help people? If so, we should put people on them.

I think try to get less caught up on, is it from a drug company or what's the source of it? But I think just really just actually track, is there good data here? To your point earlier, when I was dying from my Castleman disease, There was no data for serial limus to save my life. I had lab data that made me think it might. But sometimes you do follow the things that don't have much data because the alternative is that you're going to die, and you just do that. But if you do have data on drugs, what breaks my heart is when I hear about people with terminal cancer that say, I'm not going to take this medicine because it's a pharmaceutical product. I'm going to take something else. Then you hear about them passing away and you just think to yourself, I wish they had given themselves a shot with the traditional pharma stuff. Who knows if the pharma stuff would have worked. But we have a lot of data to show that it does work in some people. We talked about earlier, 18% of people and 20% and 25. These things don't work in everyone.

But if they work in you and they could work in you, I really want to make sure that we try it in you because the work has been done to prove that it can help some people.

What are some of the diseases that you are targeting nowadays? What are you going after? We had a brief discussion about Alzheimer's on the break here. That's another massive fear of mine. It seems to just be happening more and more. That's right.

As we shared earlier, the way that That our AI platform works is we look across every drug and every disease and basically see what matches score the highest. And so we start from there. So we don't pick a disease a priori. It's ever going to work on it. Let the algorithm point us towards a match, and then our team looks into it and we spend lots of time reviewing through them. Our team has now reviewed over 6000 of the top matches. It's out of 75 million. We got a ways to go, but 6000 brilliant MDs, PhDs reviewing through them, looking for treatments that are hiding in plain sight. Out of the ones we've looked through, we currently have six active programs. We're actually just going to add three more. We'll have nine active programs in the next month or so that look across conditions that I mentioned earlier. The example of breast cancer is one of them. That's one of the more common cancers. We've got another program in a condition called Bachman-Bup syndrome, where it's only been described in about 20 kids ever, where kids are born with this horrible rare condition where they basically...

They're hypotonic, which means their muscles don't work, so they're on feeding tubes, and they're basically bed bound, and they would be bed bound their whole lives. But there's a drug called DFMO that's been around for a long time that wasn't made for this condition, and it actually is really effective. So the kids that have been started on DFMO early in life are standing up, sitting up. Some of them are even walking. The kids that are started later on in life, maybe they are feeding tubes out, but they're not quite at the same level they would have been if they were a typical child. This is why we started this organization. It's like maybe only a couple of dozen kids are going to benefit in the short term, but maybe a couple of hundred are going to benefit in the longer term, and they're going to benefit walking to school and running with their siblings, doing things that they wouldn't have been able to do with a drug that wasn't made for their condition. Those are the kinds of things that that's just not going to... In our industry, a couple of dozen kids, no one's going to take a cheap old drug and work on a couple of dozen.

It's not that they're not going to work on it. I take that back because I should really emphasize that there's been amazing work done because the condition is called Bachman-Bopp, and that's after two doctors, Dr. Bachman and Dr. Bopp, who have done just the most outstanding work in the world to advance treatments for this condition. But the point being that Typically, that's where it would stop with this doctor and that doctor. They're doing the best they can for these kids. But us at Everycure, we're trying to find as many of these as we can. So that way, to your point, we get the word out. So if you're a child in some other part of the world and you've got this condition, let's get you diagnosed and let's get you on the medicine.

When you're sifting through the AI program that you guys have, I think you said 14,000 diseases.

Have no treatments.

Have no Oh, that's only that has no treatments.

And then another 4,000 have treatments. So it's a total of 18,000 diseases that affect humans.

Eighteen thousand diseases. How many drugs? Four thousand? Four thousand, yeah. Four thousand drugs. I mean, even with AI sifting through all that, I mean, that's a lot of stuff to sift through. And so, I mean, how does the program notify you? I mean, is there a tier ranking that says, Hey, this drug, the AI has found, may work for A spider web of diseases. Do they rank them? How do you guys sift through all of that?

Yeah. So we get a score from zero to one for every drug against every disease. So DFMO for Bachman Bop gets a score, and DFMO for breast cancer gets a score. And that's It's probably a low score because it's probably not going to work in breast cancer, but you get a score for every match. Then you look at the things at the very top, so you rank all to the less, and you say, What are the 0. 99s? Which basically the algorithm is saying, there's some heat here. There's probably something here. Maybe it's this drug, and DFM of Bachman Bups is an example, where there's too much of this thing, and this drug inhibits that thing. It's like the match is being made even at that simple of a level. In my case, there was too much of MTOR, that signaling pathway, and Cyrilimus inhibits MTOR. Most of the time, it's not that simple, but it's looking for matches like that, and it's going to give a high score if there's something clear like that. Then the other thing is we also generate a separate score. We call it our unmet medical needs score, which is basically how bad is the disease.

We score also, the higher the score, the worse the disease, lower the score, less bad the disease, because we want to be going after good matches for really bad diseases. As you said before, we're a 50-member team with limited resources. When you can go after any drug in any disease, there's a lot of opportunities. But if we're going to spend our time on Earth going after the really bad diseases with the really good matches, and so we use both scores to get us started.

Do you actually sift through each drug? It's not each disease, it's each drug.

It's actually not even each drug or each disease. It's actually each drug disease match. If you look in this spreadsheet, it's like DFMO for Bachman Bup, lidocaine for breast cancer, cirelymus for Castleman's. That's what the row is. The row is actually the match. Then there's a score next to the match. Then you might not see breast cancer again until number 10,000. The second best for breast cancer might be way below the first best, but it's actually the match that gets the score.

How many matches are there?

Seventy-five million. Because there's 4,000 drugs and 18,000 diseases. If you multiply 4,000 times 18,500, you get 75 million because you try every... Basically, we're asking the algorithm is simulate how likely each one of these 4,000 drugs would be to treat each one of these 18,000 diseases.

That is a lot of information to sift through.

It's insane. Yeah. Our team of 50, we're working really hard.

I'm just curious, how many have you been able to go through so far?

The team of 50, we've now gone through the top 6,000, and that's deep review, reviewing through to understand what data exists and why it might score well. Out of those top 6,000, we've identified, I think it's about 60 or 70 right now that have gotten what we call a deep dive, where an MD or a PhD or an MD-PhD trained person will really try to understand what are all the data for or against? Why would this drug likely work or not work? Then out of those 60 or so we've done deep dives, about 15 of those have then basically taken down to where we have a good plan. We think that if we do this clinical trial, we're going to be able to unlock this drug helping a lot of kids or adults. Then out of those, I mentioned now, the nine active programs that we're moving forward. We started as a nonprofit three years ago. We spent most of our first year doing fundraising, most of our second year really building on our infrastructure. It's really only been about one year where we've had the team working hard, going through all these scores. The opportunities, I think, are so huge.

How do you find the patients to do the studies on?

Yeah. So once we find a match that we think looks really promising, the next thing we do is find out who are the disease experts and who are the doctors that see the most patients? Is there a disease group? For a lot of these diseases, there's a parent of a kid with a disease where they've rallied around and created a nonprofit for that disease. We want to get in touch with them and understand their disease more. We want to understand what's missing. Could this drug really make a difference? And when we connect with them, it's like, We want to help your kid's condition or your condition. Will you work with us? We've raised money from the US government and from philanthropists and foundations. We're going to bring some money into here. Do you want to work with us on this? And not surprisingly, there's a lot of enthusiasm because when you think about something like Bachman Bup, those kids, the couple dozen that have ever been found, their parents probably weren't expecting that there would be a full-blown effort for their condition. And again, thankful to Dr. Bachman and Dr. Bup for all the work they've done, and we're excited to work with them.

Wow. That's incredible, man. Thank you. I love, love, love what you're doing. Thank you. What do you think about, and this is a little off the main subject here, but I've got a really good friend here. His name's Rich, and he's doing very well for himself. His whole family, multi-generational, live with him. It was his grandpa. His grandpa had... His legs were purple. I don't think he had any feeling in his toes, nothing in his feet. And he was going to a local doctor here in Nashville. And this guy told him to go to Argentina. And I believe it was stem cell. And he went down to do the stem cell somewhere in Argentina. Grandpa does a stem cell. All the color comes back into his legs within 12 hours. They're on the plane ride back home, and he's telling Rich, he's like, My feet are fucking killing me. He's like, This is horrific pain. Oh, no. Rich is like, Hey, are you okay? He goes, Yeah, I feel amazing. He's like, I haven't felt any pain in my legs in 25 years. In your opinion, why do we have to go to Argentina for things like that?

Why do we have to go to Mexico for better stem cell? What is holding the US behind on this stuff?

It's a great question because in the US, and I've wondered this, too, in the US, we do what are called autologous stem cell transplants for people with cancer all the time. That cancer, I mentioned multiple myeloma. You oftentimes treat people with their own stem cells. You basically take their stem cells out, you give them chemo, and then you give them their stem cells back. We do that. We do what's called an allogeneic stem cell transplant. We get someone else's stem cells, their bone marrow stem cells, and that can sometimes be curative for leukemia and for lymphomas. We're doing it already in some settings, but I'm not sure why some of these other settings it hasn't come forward, because some I love that the stem cell work with autologous and allogeneic stem cells. It's been 20 years that we've been doing that in the US. I'm not sure why, because what that tells me is that the US FDA is willing and they're open, when these stem cells are effective in certain ways, Maybe it's for cancer. Maybe there's a different risk profile because there's a big risk when you do these stem cell transplants for cancer.

You have a 10% chance of death within that year from the treatment. You got a 90% chance that you might be, not 90% cured, but you have a high chance you might be cured, But you got a 10% chance you're going to die from the stem cell transplant. It might be that the FDA is willing to put a stamp on that a risk when you've got a deadly leukemia and maybe less willing to put that a risk if it's not as deadly. And again, that's not from any data that I have, but that's the only way I can wrap my head around it. It's like, why do we do it here, but we don't do it over there?

Thank you for answering that.

But I don't know the full answer, though.

Well, Dave, is there anything I should be asking you that I haven't asked yet?

There's one thing you were asking me about my mom earlier, and you asked about the last conversation that I had with her, and she actually left a message for me even after she was gone. A couple of weeks after she passed away, and I actually would love to read this to your audience if it's okay. A couple of weeks after she passed away, my dad and I were cleaning out her purse, and I came across this newspaper clipping that I keep in my wallet. To me, this is like... It just embodies my mom because... I don't know if you can see, but this is basically on a piece of It's a cardboard, probably from some cereal box, and it's got some tape on it. This is just who my mom was. It's got a quote that, as you can tell, I take it everywhere with me. It's now been 21 years. It says, Pope John Paul said it best in his address to the youth in Kamigoi. Dear young people, whether you are believers or not, accept the call to be virtuous. This means being strong within, having a big heart, being rich in the highest sentiments, bold in the truth, courageous in freedom, constant in responsibility, generous in love, invincible in hope.

Like I said, I found this two weeks after she died, and I remember reading it and just thinking to myself, this is her message to me about how I need to live. Bold in the truth, courageous in freedom, constant in responsibility, generous in love, invincible in hope. And these are words that I just take with me everywhere I go. I love the idea of your listeners and your audience taking this with them as well.

Man, thank you for sharing Absolutely. Thank you for sharing that. I just want you to know it was an honor to interview you. You're changing. You are changing lives, literally saving lives. I mean, It's just better in the world. So thank you for what you're doing.

It's an honor to be with you. You're a true warrior, and we're fighting hard. We're fighting a battle. We said, 4,000 drugs, 4,000 diseases have treatments, but 14,000 don't. So we've all got to take this up. It can't just be one group here or one group there. We've got to take this opportunity to make a difference. And there's a lot of drugs out there that can help people. So we're going to keep fighting. Actually, I was telling you during the break about how we've turned the Castleman into this warrior here. This is our Castleman warrior. I've been wearing this pin for the last about 12 years. I want to give this warrior pin to you, my friend. Oh, man. You're an ultimate warrior. I appreciate you. Thank you. Thank you. Absolutely.

It's going right here in the studio. Ben, thank you.

You're a warrior, and I appreciate you giving me the opportunity to share about our work because we got a lot of work to do. It's actually going to be raising awareness through things like this that are going to help a lot of people.

Well, I'm going to tell all my friends about this, and they'll be listening to it anyways. But I hope this podcast helps, and I would love to see you again, hopefully on good terms.

I love that. Yes, exactly. All good help.

Yeah, but seriously, it was an honor. Thank you. Thank you so much.

Thank you, sir. That's awesome.