How David Fajgenbaum saved his own life—and thousands of others (transcript)

Please note the following transcript may not exactly match the final audio, as minor edits or adjustments could be made during production.

David Fajgenbaum: I've got this vision for the future. I've got the people I love by my side, and then I'm gonna take it one breath at a time. 

Adam Grant: Hey everyone, it's Adam Grant. Welcome back to ReThinking, my podcast on the science of what makes us tick with the TED Audio Collective. I'm an organizational psychologist, and I'm taking you inside the minds of fascinating people to explore new thoughts and new ways of thinking.

My guest today is David Fajgenbaum. I'd never met a more inspiring person. David's a physician scientist at Penn who saved his own life by repurposing a drug and testing it on himself. Now his nonprofit, Every Cure, has used that method to save thousands of others. 

David Fajgenbaum: I think that most physicians and researchers, they hear about a drug and they will say, that is a diabetes drug.

Well, no, it's not a diabetes drug. It is a drug that modulates this pathway and it has an effect in diabetes and it also could have an effect in all these other things. 

Adam Grant: AI is central to David's work, and it's hard to think of a more exciting use case for this technology. Just knowing he exists gives me hope, and I think he'll have the same effect on you.

David, welcome to ReThinking. 

David Fajgenbaum: Thanks so much for having me. 

Adam Grant: Tell me about the first patient you saved. 

David Fajgenbaum: Well, the first patient I saved actually was myself. Um, I was a third year med student and I became critically ill with this horrible disease called Castleman's. And I even had my last rights read to me 'cause I was getting so sick from this horrible inflammatory disease.

Spent months in the ICU, got a bunch of chemo that kept saving my life, but then I had to go on a mission to try to find a drug that I could use on myself. And I eventually discovered one and it saved my life. So I guess I'm the first patient I saved. 

Adam Grant: You say this like this is all completely within the realm of ordinary.

Okay, because you've, you've understated what happened to you, like you were on your deathbed. 

David Fajgenbaum: That's right. I have this disease, Castleman's, where your immune system just attacks your vital organs. I was on dialysis 'cause my kidneys were shutting down. I was literally fighting to survive. My doctors were sure I wouldn't make it.

And then I got chemo and I survived and then I kept relapsing. Five times I got to the brink of death and five times I just barely made it. As you know, I was a business school student at Wharton, um, at the time. So during the day I was in my, my business school classes and my nights and weekends, I was working in the lab, testing different drugs on my own blood samples, and I eventually came across this drug and I started testing it on myself.

Adam Grant: You, you hear these stories throughout the history of science about these mad scientists who no one would believe them, and so they, they inject themselves with the thing they wanna prove. And I, I think there's a major survivorship bias in these stories because the stories that, that stick are the, the people who succeeded.

David Fajgenbaum: Exactly. I mean that's, that's this whole idea, like the one in a million, it's like, yeah, the other 999,000 chances I just wouldn't have made it and we wouldn't be sitting here, you know, chatting about it. 

Adam Grant: It's, it is pretty remarkable. What was the, what was the moment when you decided you were actually gonna start testing unproven drugs on yourself? 

David Fajgenbaum: You know, I can remember the exact moment. It was May of 2012 and I was sitting in a hospital room in Little Rock, Arkansas. My dad and my sisters were around me and my doctor had just come in the room and he explained to me that I was relapsing. My liver, my kidneys, my bone marrow, my heart and my lungs were all shutting down.

And this is by, by the way, the fourth time this was happening. And what was so different about this one is he also said, and David, the only drug that's in development isn't working any longer. So there are no more drugs, there are no more promising leads. And I said, you know, Dr. Vanry, like is there something out there? Like some idea? He said, David, this is it. That was the only drug that's ever been studied and it didn't work. And I remember just like literally feeling my hospital gown was just drenched 'cause I was like bawling my eyes out. And I remember just looking at my, my dad and my sisters and my girlfriend Caitlin, and just telling them I didn't know where it came from, but I said, I'm gonna dedicate the rest of my life, however long that's gonna be. I mean, I thought it might be one week or two weeks, who knows? But the rest of my life to trying to see if I can find a drug for this disease. And, and at the same time, I also was sort of daunted by that idea, but I realized that the only way I could find a drug for my disease is if I found an existing drug and could maybe repurpose one to save me.

Adam Grant: Every time I think about your story or every time I've run into you, I have this, this sense that you're just on a different plane of existence from most people. That like I, but I think most people would love to have the clarity of purpose that you have every day, just just one day. How did you get to that?

David Fajgenbaum: I'll tell you the, the clarity I have right now is at a level that's hard to describe, and then that's that I had my last rights read to me for the first time when I was 25 years old. I mean, I was a third year med student, so I had this like clarity I wanted to become a doctor and I was on my way, but it was having my last rights read to me.

And then right around that time I got chemo and I survived. That just made life become so clear, and that was this realization that we're all in this state of overtime. And that in overtime every second counts and overtime can be really scary 'cause if you make a mistake, you know the game's over. But it can be incredibly clarifying 'cause the clock is ticking down and all you care about is like the, the the next step, the next move.

And it can be just so empowering. And so I think part of it is of course, like having your last rights read to you will sort of make you do the things that you want to do and that are important and not do the things you don't wanna do, give you a lot of clarity and purpose. But I do think that I've always, from the time I was young, have been really laser focused and sort of one thing at a time.

And so as a kid I wanted to be a college football player. And so that's all I thought about for like a decade from the time I was eight years old till I was 18. And then my mom passed away, uh, from cancer while I was in college. And that led me to want to go into medicine, but it also led me to start a group for grieving college students.

And so it's been about a decade where all I could think about was how do you support college students grieve with an illness or death of a loved one? And then now it's been a little bit over a decade on Castleman's. And of course now we're onto, um, this new initiative, Every Cure to find more repurposed drugs.

Adam Grant: You were in just a physical state where most people can't find the energy to act, but also an emotional state where, I mean, you, you must have been panicked, terrified at, at various moments. How did you overcome those challenges? 

David Fajgenbaum: I think there are three things that helped me get through it. First off, I had this vision for a future I wanted to have. I had this amazing girlfriend at the time, Caitlyn, like literally sitting by my side, my sisters on my other side, my dad there, and I could envision a world with Caitlyn, like maybe having a family one day. Like I could envision time with my sister and, and my nieces and my nephew and my dad, and I could see what I wanted and what I wanted was like, these memories with my family and, and I was 25. I didn't have a family, so I had this real clear vision and that was so important. The second is that I had them around me. I had like the people I loved, literally like locked arms with me, supporting me, like actually like holding my hand, encouraging me to breathe.

I mean, there was one point, Adam, when I was at my lowest when my doctors told, told my family I wasn't gonna make it, and, and a priest read me my last rites. At that time was when everyone was around me and I was just gonna like slow my breathing and just sort of let go. And I remember my sister, Gina. She sort of wasn't okay with that and she was like, just breathe Dave.

Just keep breathing. And I was like, I was really letting go. But I remember hearing her say that and I remember like, I can do one more breath. It's, at the time I had a lot of fluid in my lungs and so it was really painful to breathe. And if you told me, David, you're gonna be in the hospital for the next six months, there's no way I could have kept breathing. 'Cause like six months of pain, I couldn't have fathomed it, but I could do one breath at a time. And it turned out that that one breath at a time ended up adding up to a lot of months. 

Adam Grant: It reminds me of, of all the research I've read on resilience and, and I guess all the, the data I've gathered myself. I think the, the clearest lesson for me is that when other people are counting on us, we often find strength we didn't know we had. 

David Fajgenbaum: Yes. Absolutely. I didn't want to go because I didn't want to have these memories, but I also didn't want to go 'cause I didn't want put them through, yeah, the pain of me not being here. 

Adam Grant: You basically discovered a cure for your own disease. Or is it too strong to call it a cure? 

David Fajgenbaum: I, I was, I, I really, I never liked to use that. I would call it like the C word early on because, um, you sort of never know how long a drug is gonna work for. And um, you may remember this 'cause I was in business school at the time, like I started testing the drug on myself and like one month went, went by and like then like we would celebrate two months and, and they started just like sort of adding up.

And by the fifth month actually Caitlyn and I got married. We made it to our wedding day, May 24th, 2014. And so that was a huge milestone, but I was still so afraid to ever say it was a cure. Like it was working, but when's it gonna stop? And um, then there was a point around like 36 months where we started calling it like three years, and then the years have kept adding up.

Adam Grant: And you're adding, this is 11 years now. Congratulations. 

David Fajgenbaum: 11 years. Thank you. Yeah. And, and it just, I'm still a little afraid to use the, the, the word cure, but of course my book is called Chasing My Cure. And, and my friends, they know, I like never say the word cure. They're like, can't believe you titled your book cure. And then of course now I have a nonprofit. 

Adam Grant: Every Cure.

David Fajgenbaum: With Every Cure, and it's like, wait a minute. What? I thought you wouldn't use that word. 

Adam Grant: Well, I think, I think it's the goal that you're always chasing. 

It is. 

David Fajgenbaum: Exactly. It's the goal. That's exactly right. 

Adam Grant: Or maybe, maybe be even better to describe it, it's the mission. 

David Fajgenbaum: It's the mission. 

Adam Grant: Minimum, you found a more effective treatment than had ever existed before. How many people have Castleman's? 

David Fajgenbaum: There are about 5,000 patients diagnosed each year in the US, so it's a, it's a rare disease, certainly, but not the rarest of the rare, and right now there's an FDA approved drug that works for about a third of patients.

And then the drug that I discovered works for another about 20% of patients. 

Adam Grant: Wow. So how many, how many lives have you extended through that discovery along with your own? 

David Fajgenbaum: It's hard to, you know, quantify exactly, but certainly in the thousands.

Adam Grant: It's incredible. 

David Fajgenbaum: It's amazing. I get to meet kids who like literally are, you know, going off to college that just should, shouldn't be here if not for this drug.

It's incredible. 

Adam Grant: I think that there are a lot of people who would make that discovery and say like, this is the meaning of my work, if not my life, and I'm just going to pour myself only into that. When did you realize that there was an even bigger opportunity for impact? 

David Fajgenbaum: It was sort of, I'd say almost like one moment, one patient at a time.

The drug worked for me and then it worked for the next two patients we treated and we're like three for three. Like, oh my gosh, this is gonna work for everyone. And then there were a few patients in a row where it didn't work. And you know, Adam, we've talked about this before. I'm so motivated and get so excited about all these patients we help and then equally, or maybe even to a greater extent, the patients were not able to help are just like the ultimate motivator, like we have to figure this thing out. And so here I am, like alive thanks to this repurposed drug, and I'm like, gosh, we gotta find more of these for other people. And so shortly after we started testing this drug, sirolimus, on other patients, we started looking for other drugs that could work for Castleman's patients.

And we discovered a drug, uh, that we treated a young, a young patient with, a girl named Kyla. Um, the drug's called Ruxolitinib and that drug saved her life. And that moment of like, wait a minute, okay. Like, we did this once before and maybe it was like, like I said, like the one in a million, like, but now we did it again.

And then I gotta hear about Kyla who had spent a year in the ICU, like going back to school and like I learned about her favorite games that she loves to play. And like that, that for me was this like, oh my gosh, we have to keep doing this. Like there's more out there. And right around that time, my uncle actually was diagnosed with a horrible, rare form of cancer called Angiosarcoma.

And I went down to visit him and my family and actually went with him to a doctor's appointment. And I learned that there was a study that was done three years earlier. It was a laboratory study that suggested a drug might work for his form of cancer. Uh, and I brought it up to his doctor and his doctor said, well, it's never been used before.

Like, you know, these drugs that, that are tried and true, they didn't work. He needs to get ready for hospice care and transition into hospice. And we found another doctor and we, um, tested his tumor. It came back positive and, and we thought it might work. And so we got my uncle on this drug called Pembrolizumab and it saved his life and it'll be, uh, nine years in April.

So just in a couple months. And like these wins were like, so exciting. And they also were so depressing 'cause it was like, wait a minute. Like how is this information out there? Like I just found it on PubMed, like I searched for it and I found it. Like, how are we as a system like letting things like this fall through the cracks?

Adam Grant: That's exactly what I was just wondering. Why has this not been done before? 

David Fajgenbaum: So I would say it's like hard to understand, but we've spent so much time looking into it. A lot of it really comes down to dollars and cents. 

Adam Grant: That's what I was afraid of, it's incentives. I'm assuming a lot of these diseases are rare and there's not a lot of money to be made and in treating them.

David Fajgenbaum: That's exactly right. There's two factors in what's gonna make a drug profitable. There's how expensive is the drug and how big is the population? And so if it's a really expensive drug, drug companies will actually pursue that even for a very tiny population. And if it's a really big population, drug companies will pursue even inexpensive drugs.

But if both of those change, if you've got an inexpensive drug and a rare population, or just a very inexpensive drug, it doesn't matter how big the population is, the incentives just aren't there for anyone to, to profit from selling more of this drug. And so it's not that people are sitting on this information and that it, they don't wanna get it out there, it's just that there's no incentive to act on the information.

Adam Grant: I also wonder about the, the psychological hurdles that people have to jump over. I'm thinking about what's, what's called functional fixedness. Have you come across this? 

David Fajgenbaum: I haven't, no. 

Adam Grant: It's a, it's a classic idea in psychology that when, when we come across an object or a resource and it has a particular use, we, we tend to sort of limit ourselves to only assuming it, it serves that purpose. 

David Fajgenbaum: There's a, a very famous drug that, that all the listeners will have heard of: Viagra. We, we all know what its current use is, and some people may even know that it was initially studied for heart disease, but actually it's been repurposed for a rare pediatric lung disease. So kids were literally dying before they reached their teenage years 'cause they weren't getting enough blood flow of their lungs.

Now with Viagra, they can live full lives. There are even more examples of things like thalidomide, where they've been repurposed. But the problem is, is that we always think about the first use and we oftentimes prevent ourselves from thinking creatively of these other uses. And so you're right, it, it's both this functional fixedness and it's also this financial hurdle that we're up against.

Adam Grant: So let's talk about how to overcome each of those. When it comes to functional fixedness. My first thought is, people are are really good at an analog reasoning. So when you start to give the Viagra example, I think the average scientist or physician ought to hear that and say, oh, I wonder what other drugs this would work for.

Is that what happens for you? 

David Fajgenbaum: It is exactly what happens for us. We associate these things together, the drug and the condition, but at Every Cure, the whole idea is that the, the world of possibilities are out there. Every drug we evaluate against every possible disease. 

Adam Grant: So how are you solving the incentive problem then?

David Fajgenbaum: So the incentive problem is, is really tough to persuade others to go after inexpensive drugs for rare diseases. We've basically decided that we're gonna go after these opportunities that others aren't going after. We're a nonprofit, we don't need to, to profit, so we are actually going to pursue the non-profitable opportunities. And just today, you and I were chatting about, um, one of those opportunities that we're pursuing, that's a, a cheap old drug called Leucovorin, which is actually just a vitamin derivative, for a rare subtype population of people with autism, and so this is an example where you've got a cheap drug that clearly works.

There's been three trials that have shown that it works, but the incentives just aren't in place to get it to more people.

Adam Grant: How does Every Cure work? It sounds like you have a couple of major functions. One is to do the matching. I'm picturing a diagram with a long list of diseases in one column and then a list of drugs in another column. 

David Fajgenbaum: That's right. Yeah. And we, we call it The Matrix. And so it's basically, there's 4,000 approved drugs and there's 18,000 diseases.

So if you tried every drug on every disease, you would try 75 million combinations. 

Adam Grant: Wow. 

David Fajgenbaum: And so we utilize an AI platform that literally looks across all of the world's medical knowledge and gives us a score from zero to one for all 75 million possibilities. And we started the organization a couple years ago, we ran the algorithms for the first time about two years ago, and it took us a hundred days to get the results. A hundred days for this algorithm to literally look across all the world's knowledge and come up with scores. And now we're down to about 17 hours to run the algorithm. 

Adam Grant: You get a score that says, okay, 88% probability that this drug is gonna help with this disease.

How accurate is that? 

David Fajgenbaum: Good question. So the percentage, I don't think is accurate in the sense that we don't, you know, when we get a 0.88, we don't say it's 88%. We say that it's higher likelihood than the 0.62. 

Adam Grant: So the rate order is what matters. 

David Fajgenbaum: Exactly. It's a relative score. The AI platform gives us a score for every drug versus every disease.

So Leucovorin for autism, you know, Cetuximab for Castleman's, you name it. And then our medical team reviews through the things at the top, and we ask strategic questions like, how much unmet need is there? How much suffering is there? Does this affect kids? Does this affect adults? How expensive is the drug? And then we apply these filters to the things at the top, and out comes these incredible repurposing opportunities that could help a lot of people.

And then for us, we have to decide, um, what needs to be done next. So in some cases, you gotta work in the lab to really prove that this thing's really likely to work. Sometimes you gotta do big clinical trials, and sometimes you just have to put a spotlight on it. 

Adam Grant: I guess you could go okay, let me take a, a couple of scientists who are the world expert on this disease and introduce them to a bunch of drugs they don't know exist.

Are humans adding anything at this point? If we're in the loop? 

David Fajgenbaum: The thing about what we're doing that humans can't do is that you can have experts for a disease, you can have experts for a drug, and they can do a good job of matching. What humans can't do is to compare leucovorin for autism versus arginine for folic acid deficiency, right? Like there we're not able to do that sort of combinatorial comparison. And so I think that's what's really transformative here is to use AI to look across everything. What we're doing with Every Cure is actually looking across the entire forest to say what's the lowest hanging fruit across the whole forest, not just for, you know, one disease or one drug.

Adam Grant: Okay. So sort of first phase of Every Cure is you're doing this drug discovery and matching process. 

David Fajgenbaum: Yeah. 

Adam Grant: Then second phase, you run trials when you have promising options? 

David Fajgenbaum: Yeah. So in some cases we find that, that more lab work is needed before we go to a clinical trial. Where like there's something promising, there's this really interesting evidence and, but we wanna study it more in the lab.

And so whereas in other cases it's ready for a clinical trial. And those are of course the most expensive aspect of this whole process. And then in some cases, like leucovorin for autism, it's ready for awareness raising. There've already been three clinical trials. It clearly works. We just gotta let people know that it's out there.

Adam Grant: Okay. And then awareness raising then is, is sort of the third branch? 

David Fajgenbaum: Exactly. Awareness raising. And this is somewhat similar to what drug companies do with, you know, with pharma sales, but it's also sort of advocacy related 'cause we're a nonprofit and, and we don't make any money when drugs get, you know, used or sold.

So, um, we're sort of trying to build the plane while we're flying it. 

Adam Grant: I'm reminded of a great observation from Carl Wyke who said that creativity is just putting old things in new combinations and new things in old combinations. Does it sound familiar? 

David Fajgenbaum: It sounds perfectly familiar and honestly, I have to say, when I, when I saw your book coming out, Hidden Potential, I was like, oh, Adam's written a book about drug repurposing.

This is great. And, and Think Again, another drug repurposing book. I'm like, this is amazing. 

Adam Grant: You know what? I, I never thought of that, but you, you live in the center of that Venn diagram. 

David Fajgenbaum: Exactly. I was like, oh, great. A drug repurposing book. 

Adam Grant: I, I should just ask you what my next book should be about. 

David Fajgenbaum: You know what?

I think no matter what the book is titled, I will think it's about drug repurposing. 

Adam Grant: I think what's so inspiring about it, aside from you. I think about biopharmaceutical and medical innovation as a very slow process and what, what you're drawing our attention to is the fact that actually a lot of the solutions we need already exist.

We just haven't looked in the right places yet. 

David Fajgenbaum: That's exactly right. And, and where are we putting our time, our attention, and where are we investing artificial intelligence? We're investing in new drugs for new conditions and no one's using AI to do what we're doing 'cause there's no upside to it. It's sort of like depressing that we're in this position and that, that it really does come down to dollars and cents.

But it's also really exciting 'cause that means that there's a lot of stuff out there to help a lot of people. 

Adam Grant: I wonder about the broader idea of repurposing and where it applies outside of drugs and diseases. Have, have you had any time to think about that? 

David Fajgenbaum: Yeah, there's a few that come to mind. So the very first telephones were invented to be hearing aids.

And so like the hearing aid became the telephone, of course, we're all familiar with the fact that computers were initially intended to actually track results from the US census. And of course we use them in very different ways today. And actually the very first radios for like, actually disseminating music was, was just a tool for ships to communicate with one another in the open ocean.

I mean, think about MacGyver there, there's a, there's a lot of ways to use things in new ways. 

Adam Grant: Yeah. I'm, I'm thinking about Stewart Butterfield who founded Slack, which originally he, he launched a video game company.

David Fajgenbaum: Really? 

Adam Grant: And he didn't like any of the existing tools for communication, and so they built Slack and then the video game company didn't survive, but the tool they built of course took off.

David Fajgenbaum: I love that. 

Adam Grant: One of the reactions I've seen people have to you is no one is that good. What are your vices? 

David Fajgenbaum: I really do struggle to switch from the things that I'm focused on out of that. Like when I'm focused in on something, like I just wanna do it for like 16, 18 hours a day and do nothing else. And that's actually a problem for like family and friends and loved ones, 'cause like you have to be able to switch in and out. 

Adam Grant: Part of what I hear you describing is the difference between harmonious and obsessive passion, or is what, what Nancy Rothbard has called being a compulsive workaholic as opposed to an engaged workaholic. 

David Fajgenbaum: Yes. And, and that's something I've just always struggled with. And I will say that I am, um, I'm a proud uncle of, um, two nieces and a nephew and, um I have been called Uncle Unfun before because I've been so focused on like, are they wearing their helmets? Like, do, do they have knee pads on? So I'm, I feel like I'm, I'm channeling that right now. 

Adam Grant: Uncle Unfun, that's one of the, the least unpleasant insults when you think about the actual meaning of it.

David Fajgenbaum: That's right. 

Adam Grant: Uh, but also a little bit disappointing at some level. 'Cause the, the whole role of an uncle is to be fun. 

David Fajgenbaum: Must be fun. I know. Yeah. It's like the fun uncle. They're like, actually was like called Uncle Unfun. 

Adam Grant: Angela Duckworth and I have talked a lot about what's the dark side of grit. One of the common traps that grit leads us into is escalation of commitment to a losing course of action.

Where we start throwing good money after bad and investing our time in failing projects and pursuing things that, that just don't make sense. And I think what Angela and I have aligned on after years of debate is that that's more likely if your grit is narrowly invested in a path as opposed to broadly applied to a goal.

And I, I, I wanted, I wanted to get your, your take on this 'cause you've experienced it directly. I, I think in your world it would be really counterproductive to, to become sort of hell bent on proving that a particular drug is going to work for a particular disease. But if you're attached to the broader mission of finding a cure or a treatment for a given disease, that keeps you open-minded and flexible. Talk to me about that.

David Fajgenbaum: That's exactly right. I mean, the other thing I would say for me and for our team is just having a really, really incredible and also diverse team of people that are looking at problems from different angles. I might, given my tendencies, you know, get really, really focused on this one thing, but having an amazing team that's empowered to be able to say, well, actually, that's not what the data's telling us. Let's actually look over here at this other opportunity. I found that to just be essential. 

Adam Grant: You clearly love to help people, and I think that you must be in a difficult position now of there are so many different diseases that you could tackle. There are so many different drugs that you could test, and also everyone who's ever met you now knows that you're the person who might be able to save the person they know who is in a situation where they can't get a treatment.

Do you feel the weight of the world on your shoulders? And do you, do you feel like it's impossible to ever set a boundary or say no? 

David Fajgenbaum: Yes. Um, I, I, I do, it feels like the weight of the world. The way that we are handling it is that we utilize our AI platform to look at all drugs versus all diseases, to make it as unbiased and as disease and drug agnostic as possible.

So then we can pick the best opportunities, which leads us to have really heartbreaking conversations with groups that'll come to us and say. We want you to find a drug for our disease. And I would love to find a drug for their disease, especially as you hear the stories of, of the suffering that they're going through. And we have to explain to them that the way that Every Cure works is we look across everything versus everything. And I really hope we're gonna find a drug for your disease when we look across everything. But we can't begin by just focusing on one disease or another. And I mean that, it's just heartbreaking to say that.

It's also just motivating for us to say, well, that means we need to get through a bunch of things. 'Cause like if your disease isn't number one and it's number 55, we better get to number 55 as quickly as possible. 

Adam Grant: Yeah. That becomes a, a reason to grow, for sure. 

David Fajgenbaum: Exactly. 

Adam Grant: And the reason to accelerate your process.

You always seem so joyful though, when I see you. I, you don't seem, it doesn't, it doesn't seem like you're feeling a tremendous amount of pressure or stress. 

David Fajgenbaum: No, and I, I think this partly comes down to that sense of overtime when you've looked at your family and friends and now my wife and said goodbye to them, and you just have this incredible appreciation that sort of allows you to look at the positive and, and just you know, feel the joy in life and to, and, and to, I, I think to have that sort of mindset. I've mentioned my mom briefly. Um, she passed away 20 years ago from cancer. Her spirit was such a positive spirit, and I, and I learned from her. I spent almost 20 years of my life. I. With her. And I think that there were just a lot of lessons I learned from her about how to, um, be positive in the midst of challenging times.

She, she taught me this one lesson, I think about all the time, Adam, and that's, she would say, David, during difficult times, we're often encouraged to look for silver linings, but we shouldn't just look for silver linings. We should look to create silver linings. Creating silver linings is saying, okay. I've been sick. This has been really horrible. I'm gonna create an organization to be able to fix this problem so that way other people don't have to go through it and, and like, she told me this back then and I didn't know that then years later I would then be like, oh my gosh, this is the silver lining you have to create.

Adam Grant: I wanna go back to your, your criteria for how you decide what to prioritize. It sounds like the number of people affected is a, is a big consideration. 

David Fajgenbaum: So we've actually gone back and forth a lot on that. It's the amount of suffering for a given condition. And so a condition that affects a lot of people but has very limited suffering will actually, in aggregate, score not as well as something that causes horrible suffering in a small group of people.

Adam Grant: Good, as it should be. 

David Fajgenbaum: As it should be. 

Adam Grant: That, that seems roughly aligned with the principles of the effect of altruism movement. 

David Fajgenbaum: That's right. And I actually hadn't thought about it that way, but yes, I mean, it's, it's really about using dollars efficiently to relieve suffering. And, and I, and we have intentionally said the size of the disease should not weigh in to the same level that the amount of suffering does.

And it's in part because we know that's where the biggest gap in the system is. We know that like we should be going where other people aren't. 

Adam Grant: Quantifying suffering is so hard, though. I think this has been one of the real challenges for effective altruism. You do have some, you know, some very clear binary outcomes.

I think, you know, mortality versus survival is, is probably an easy one for you. But when it comes to then asking, well, you know, how many years of life could we add versus how much pain could we take away or minimize? How, how do you think about those, those gray area calculations? 

David Fajgenbaum: It's really tough. We have something we call an impact score that tries to do this and, and we use a, a variety of machine learning models to scrape across lots of data around the world.

And it's the best we can do in this very quantifiable way. But then at the end of the day, we're still left with, do we want to pursue lidocaine for this horrible form of cancer, or do we wanna look at this agent for sickle cell disease? And comparing across them is just really hard to do. So we struggle with it.

But one thing we do that is helpful is we do talk to patients with those conditions, and that helps us to get just a better understanding for which of these we're able to go after.

Adam Grant: All right. Let's go to a lightning round. First question, what is something you've rethought lately? 

David Fajgenbaum: When we first started Every Cure, I thought we were gonna find a lot of early promising drugs that had a lot of work left to be done. What I didn't think we would find, and I've been really surprised about, is how many drugs have been actually advanced very far. And there's very little left to do, left to be done. And what's exciting about rethinking in that way is that you can actually make major impact with really small dollar amounts because someone's already done all the hard work. 

Adam Grant: What's the worst career advice you've ever gotten? 

David Fajgenbaum: The worst career advice I ever got was to stick the course and continue to do residency training after medical school, go into practice like you were always gonna do. And I got this advice from people that I really respect, but it was, I, because I had nearly died from this disease so many times, I almost felt like, um, I don't know the, the permission or just the ability to just not listen to that advice and say, I'm gonna do the thing that I wanna do. 

Adam Grant: Do you have a, a favorite piece of advice you've received?

David Fajgenbaum: The number one thing that just goes through my head all the time is that hope is really important and we should be hopeful and we should reflect on, on what our hopes are, but hope is not enough and that hope should then turn into action. 

Adam Grant: If you look out 10, 20, 30, 50 years, what's your boldest prediction for the future of medicine?

David Fajgenbaum: Wow. I think looking that far out, I think that we are really going to uncover so many treatments for so many diseases. The one challenge I think we're gonna have to, to solve for is how do we make sure that those treatments for diseases where there isn't a, a financial path forward, do they actually reach people?

Adam Grant: I'd love to hear a hot take, uh, an unpopular opinion that you're eager to defend. 

David Fajgenbaum: When we try to solve problems, we oftentimes think about is there a smart solution? You know, work smarter versus work harder. And what I've sort of recently just become aware of with myself is that I, I think the best solution is, is both, right, is the smart and the hard one.

I think taking the hard solution creates some intrinsic value for you and for your team, that like you took the hard road and you still got through it. So it's probably not what you should teach in business school as like to take the harder path as opposed to take the smarter path. But I think there's something just like from a team building perspective and from like a, a value perspective, I think going the harder path, I think you get more out of it.

Adam Grant: Fascinating. It actually tracks with, with some evidence suggesting that like when, when economists say like, effort, effort is aversive, people don't like hard work. Uh, people don't always enjoy hard work, but we do derive a lot of meaning from it.

David Fajgenbaum: I think so.

Adam Grant: What's a question you have for me? 

David Fajgenbaum: You have seen so many people, you know, repurposing concepts and solving problems with solutions that are hiding in plain sight.

When you look at what we're doing, and maybe you even take out that it's, you know, drugs for diseases, but but certainly could be in that context, what do you immediately say, David, you should be thinking about this, or, or have you thought about that? 

Adam Grant: If I were in your shoes, I would not give up so quickly on pharma saying this is not a profitable drug. Pharmaceutical companies desperately need wins right now when it comes to public opinion and trust. Thinking about the, the post covid sort of conspiracy theories. 

David Fajgenbaum: Yeah. 

Adam Grant: Skepticism, deep seated, you know, senses of betrayal. Frankly, there's a, there's a big PR opportunity for major pharma companies to show that they're willing to do something good that they didn't get, uh, you know, a financial gain from. And I don't know whether that is partnering with their foundations or whether that means, you know, starting a joint initiative that they would fund, but I, I think there's, there's an opportunity there. What do you think? 

David Fajgenbaum: I, I love that. I mean, from the very beginning I've dreamed of this world where like we work hand in hand with pharmaceutical companies. They tell us like, we thought about this drug being used in this other disease, but we weren't able to pursue it for commercial purposes, but we want you to pursue it. Or maybe we'll pursue it together. Because at the end of the day, no one understands drugs the way that the drug companies that made those drugs understand them.

And I think we need to get one or two wins under our belt where like one of these companies comes to us, they share an idea or we come to them and we, and we work together because I agree that there is some, there is some real untapped and hidden potential there. So, yeah. No, I, I love that. 

Adam Grant: Are, are you already having these conversations with pharma CEOs?

David Fajgenbaum: We've had a lot of conversations with the first concept I had, which was can you tell us the additional diseases that you thought about but never pursued for your drug? Because what we've learned is that the average drug that ends up getting an FDA approval will typically have somewhere around 20 diseases that they thought about for that drug, and they ended up getting it approved for one or two diseases.

So there's a lot of other diseases they thought of, and there was good rationale, but they never pursued. But what I've learned is that the information isn't always well organized. It's sort of in one person's brain and someone else's PowerPoint, and that there isn't an easy path for them to share.

They've just never done that before. And so I'm sort of running into barriers of like, is the information there and if it is there, is there, are there easy ways to share it? What are the legal implications for the company? And I'll, I'll just admit that I've just gotten a bit frustrated that we haven't been able to to solve it yet.

But if there's a listener here who's in the industry and would like to think about how to solve it, I would just love to because I think there's so much potential there. 

Adam Grant: I, I think so too. What's the biggest chasm between where you are and where you want to be right now? Is it just the funding to be able to do more lab testing and more trials?

David Fajgenbaum: Yes, it, it's always gonna be the gap between the funding we have and the funding that, that we could utilize to save more patients' lives. I mean, the bottom line is that there are hundreds, potentially thousands of repurposed drugs waiting to be unlocked. So, so as we mentioned earlier, for us to get from, you know, number five, down to number 55 really does require significant resources.

And also I, I'd say from an organizational perspective, I think the biggest, um, gap or opportunity for us is really to expand what I consider like the last leg of the relay, which is like we're, after all the lab work's been done, after all the trials have been done, the drug definitely works, but now we gotta get it to people.

This is just a, a, a bit of a whole new world. No nonprofit has ever been disease agnostic and drug agnostic, or no entities ever been agnostic to those and just wanted to help people regardless of what the condition is or what the drug is. And so, again, if there's any listeners on here who, um, who are great at in marketing and, and have pharma sales experience, you know. We need, we need to build that muscle. Um, because we gotta, we, we, that that is one piece of this, um, that AI is not gonna solve. Um, and that we have to really get to get to patients. Maybe I've just turned to you for, for advice, this is sort of general advice, but could also be applied to this specific example of leucovorin and autism.

So we've got data that shows that the drug works, it's an inexpensive drug, and there's all these people who can benefit from it. What would your marketing strategy be? What would your sort of strategy for how do you get this drug? Again, it could be another one, but this drug to people who could benefit.

How would you think about that process? 

Adam Grant: I'd start with your best before and after story. 

David Fajgenbaum: Hmm. I love that. 

Adam Grant: I, I think that's the easiest one, because I mean, in, in this case you're talking about, someone with autism who was, had limited verbal capacity and all of a sudden is talking. What's, what's the best example you have?

David Fajgenbaum: Yeah. This young patient named Mason, who he had nonverbal autism, was nonverbal, uh, for three years and within three days of starting Leucovorin began to speak. And this was just sort of mind blowing to hear that story. And then when you combine that with the fact that there's three clinical trials that prove it out in larger numbers, but I love that you're going to the, to the anecdote of the patient, because for me as a physician and as a scientist, I often go to the clinical trials. Let me tell you about the trial from India and from France. But I think we need to lead with the personal story. 

Adam Grant: I think so too. And then, by the way, here's all the evidence that this is not a, an isolated case.

David Fajgenbaum: We probably should take a moment to laugh about how when I came to you a few years ago with my idea for what is now called Every Cure, it was initially called the Matrix Drug Repurposing Initiative. Matrix. 

Adam Grant: You were gonna have to rename yourself Neo. 

David Fajgenbaum: That's right. And Matrix was an acronym, so it was an acronym and it was called MDRI.

So it was like a double acronym. And I remember I sent it to you and, and one of your postdocs at the time and you kindly said, I think you guys can do better than that. And I'm so glad you did. And so we, we renamed it Every Cure. With Every Cure, we wanted to be really bold and just say, we believe that every drug that's out there that's on the pharmaceutical company, or on the pharmacy shelf, should be utilized for every disease and every patient possible.

Adam Grant: I am really glad that you rethought that name quickly. Although you could have, you could hire Morpheus. 

David Fajgenbaum: That's right. 

Adam Grant: That would be cool. 

David Fajgenbaum: We could have 

Adam Grant: some red pills. 

A spokesperson. Yeah. David, rough calculation. How many lives have you saved? 

David Fajgenbaum: We're certainly in the thousands. Always hard to get specific numbers because there's a lot of people that we save who I learn about years later, and they reach out to me by email. Certainly in the thousands, maybe even in the tens of thousands.

Adam Grant: How does that make you feel? 

David Fajgenbaum: It's incredible. And, and it's incredible because each one of those patients that I get the chance to meet, I hear about these life experiences that they had. And what I think brings the most joy is not just hearing that someone has had their life extended, but it's hearing about what they did in that extension.

So this one patient who had angiosarcoma, who then was able to walk his son down the aisle eight years after his diagnosis when he shouldn't be here. And it was this girl, Kyla, who was able to begin her freshman year of nursing school after she never should have survived from her condition. It's hearing about those, the things that were enabled as opposed to the horrible thing that was prevented.

That just is incredible. 

Adam Grant: It really is. Well, the, I think the work you do is, it makes me feel moral elevation, uh, which is maybe my favorite emotion in psychology for when you see somebody whose example of excellence or kindness or pick your virtue is so uplifting that you want to be a better person. And that's the effect I think you have on, on everyone who knows you, uh, along with the, and what am I doing with my life?

David Fajgenbaum: You have been such an awesome supporter and I so appreciate you. You taking the time to like, give me concrete advice, but also you taking the time to connect me to people. Just, it really means so much. So thank you. 

Adam Grant: I can't save people's lives directly. It's not my expertise. But if I can help someone who does, then that makes my work much more worthwhile. 

David Fajgenbaum: And it, , and it's so appreciated.

Adam Grant: Well, thrilled to have you here. It's, it's been a long time coming. 

David Fajgenbaum: This has been so fun.

Adam Grant: David reminds us that good ideas are abundant, but good execution is scarce. The dots are out there just waiting to be connected. So what are we waiting for?

ReThinking is hosted by me, Adam Grant. The show is part of the TED Audio Collective, and this episode was produced and mixed by Cosmic Standard. Our producers are Hannah Kingsley Ma and Aja Simpson. Our editor is Alejandra Salazar. Our fact checker is, Paul Durbin. Original music by Hans Dale Sue and Allison Layton Brown.

Our team includes Eliza Smith, Jacob Winnick, Samaya Adams, Roxanne Hai Lash, Banban Cheng, Julia Dickerson, Tansica Sunkamaneevongse, and Whitney Pennington Rogers.

One more thing, last year I was at an event with David and Penn and Kim Holderness did a hilarious song that included a little shout out to him. Enjoy. 

Penn Holderness: Oh, hey there. Your name's David. What'd you do? Oh, you died five times and then you paid back your life five times, and you took blood samples of yourself and you cured your own fucking disease and you're super hot. You look like a Disney prince.