EP. 73: THE PHYSICIAN WHO CURED HIMSELF
WITH DAVID FAJGENBAUM, MD, MBA
An immunologist describes his multiple near-death experiences as a patient with Castleman disease, shares how he found his own cure through self-experimentation, and discusses his current efforts in discovering treatments for rare diseases.
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Episode Summary
As a medical student, former college quarterback David Fajgenbaum, MD was at the peak of his health and physique when he suddenly came down with a mysterious disease that, within weeks, led to multiple organ system failure. Dr. Fajgenbaum found himself on the brink of death over and over again in the intensive care unit, at one point receiving his last rites, with all of his doctors baffled about the cause of his illness. When the culprit was eventually found to be Castleman Disease, a rare disease entity that to this day defies categorization, he took matters into his own hands, researching and testing treatments on himself before finally discovering his own cure. Today, Dr. Fajgenbaum is not only the co-founder of the Castleman Disease Collaborative Network, but is leading efforts to discover therapies for other rare diseases. He is the author of the 2019 memoir Chasing My Cure. In this riveting conversation, Dr. Fajgenbaum shares his incredible, inspiring story to turn hope into action.
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David Fajgenbaum, MD, MSc is an Assistant Professor of Medicine in translational medicine and human genetics at the Perelman School of Medicine, Founding Director of the Center for Cytokine Storm Treatment & Laboratory (CSTL), Associate Director of Patient Impact at the Penn Orphan Disease Center, and President and Co-founder of the Castleman Disease Collaborative Network (CDCN). He is the author of Chasing My Cure: A Doctor’s Race to Turn Hope Into Action and he is a patient battling idiopathic multicentric Castleman disease (iMCD). An authority on cytokine storms and their treatment, Fajgenbaum launched the CORONA project in March 2020 to identify and track treatments for COVID-19.
He has published scientific papers in the New England Journal of Medicine, Blood, and Journal of Clinical Investigation. Dr. Fajgenbaum co-founded the CDCN in 2012 to accelerate research and treatments for Castleman disease through a ‘Collaborative Network Approach,’ a business-inspired approach to biomedical research, which has become a blueprint for advancing rare disease research. He is Co-director of the advisory committee for a FDA/NIH/C-Path public-private partnership called the CURE Drug Repurposing Collaboratory, and lead investigator for a collaboration with the Chan Zuckerberg Initiative to advance rare disease drug repurposing.
Dr. Fajgenbaum earned his MD from the Perelman School of Medicine at the University of Pennsylvania, where he was a 21st Century Gamble Scholar. He received his MBA from The Wharton School, where he was awarded the Joseph Wharton Award, Core Value Leadership Award, Kissick Scholarship, Wharton Business Plan Competition Social Impact Prize, Eilers Health Care Management Award, Mandel Fellowship, and Commencement Speaker.
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In this episode, you will hear about:
• How the loss of his mother to cancer led Dr. Fajgenbaum to pursue a career in medicine - 2:13
• The rapid deterioration from peak physical health to multiple organ system failure that struck Dr. Fajgenbaum - 6:04
• Dr. Fajgenbaum reflects on the terror of his unknown affliction and how he maintained resilience - 12:59
• How a brief remission gave Dr. Fajgenbaum an opportunity to turn passive hope into action - 21:47
• How a relapse led to a series of experimental treatments and a realization that his cure might already exist - 24:47
• How deep research and self-experimentation led to a breakthrough - 36:42
• Dr. Fajgenbaum’s nonprofit Every Cure and its mission to discover new uses of existing drugs - 42:02
• How Dr. Fajgenbaum feels when he cares for patients in similar plights to his own prior - 47:03
• What clinicians can do to comfort patients even when treatment options are limited - 51:37
• Advice to clinicians and students who are interested in medical research - 53:25
• Lessons on presence and compassion that Dr. Fajgenbaum has learned from having been both physician and patient - 56:32
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Henry Bair: [00:00:01] Hi, I'm Henry Bair.
Tyler Johnson: [00:00:02] And I'm Tyler Johnson.
Henry Bair: [00:00:04] And you're listening to the Doctor's Art, a podcast that explores meaning in medicine. Throughout our medical training and career, we have pondered what makes medicine meaningful. Can a stronger understanding of this meaning create better doctors? How can we build healthcare institutions that nurture the doctor patient connection? What can we learn about the human condition from accompanying our patients in times of suffering?
Tyler Johnson: [00:00:27] In seeking answers to these questions, we meet with deep thinkers working across healthcare, from doctors and nurses to patients and health care executives, those who have collected a career's worth of hard earned wisdom probing the moral heart that beats at the core of medicine. We will hear stories that are by turns heartbreaking, amusing, inspiring, challenging and enlightening. We welcome anyone curious about why doctors do what they do. Join us as we think out loud about what illness and healing can teach us about some of life's biggest questions.
Henry Bair: [00:01:03] As a medical student, former college quarterback David Fajgenbaum was at the peak of his health and physique when he suddenly came down with a mysterious disease that within weeks led to multiple organ system failure. Dr. Fajgenbaum found himself on the brink of death over and over in the intensive care unit, at one point receiving his last rites, with all of his doctors baffled about the cause of his illness. When the culprit was eventually found to be Castleman Disease, a rare disease entity that to this day defies categorization, he took matters into his own hands, researching and testing treatments on himself before finally succeeding in discovering his own cure. Today, Dr. Fajgenbaum is not only the co-founder of the Castleman Disease Collaborative Network, but is leading efforts to discover therapies for other rare diseases. He is the author of the 2019 memoir Chasing My Cure. In this riveting conversation, Dr. Fajgenbaum shares his incredible, inspiring story to turn hope into action. David, thanks for joining us and welcome to the show.
David Fajgenbaum: [00:02:11] Oh, thanks for having me.
Henry Bair: [00:02:13] I'm really excited to explore your journey and your battle against Castleman Disease. But before we get into all of that, can you share with us what drew you to a medical career in the first place?
David Fajgenbaum: [00:02:24] Sure. So I had always been really interested in health, exercise, diet. I actually I dreamed of one day playing college football. That was sort of what I thought about as a kid, but I never really knew that I wanted to go into medicine until I went off to college. And shortly after I got to college, my mom was diagnosed with brain cancer and that experience of her diagnosis with brain cancer and then watching her battle over the next 15 months really was what drove me to say I want to dedicate my life to searching for treatments for people like my mom to take care of people like my mom. And so it was it was that experience as a 18 year old freshman in college that made me say, this is all I want to do and I'm going to dedicate the rest of my life to trying to find treatments for patients like my mom.
Henry Bair: [00:03:08] So did you want to become an oncologist? Going to medical school?
David Fajgenbaum: [00:03:13] That's right. I wanted to be an oncologist. And I was, I guess you could say, well, on my way, when all of a sudden, as you know, I became the patient myself.
Tyler Johnson: [00:03:22] So, David, before we go to talking about you becoming an oncologist, specifically, if we can just back up for a second. You know, we've talked to a lot of people, of course, who are health care practitioners, a lot of doctors in particular, and other health care practitioners on the show. And many of them have origin stories that involve some close scrape with illness when they were young, whether it's in themselves or in a family member. But we've also talked to some people who are not directly in medicine, and some of them also have an origin story that involves a close grip with illness when they were younger. But it's just so interesting to notice that many of the people who end up not going into health care say, oh my gosh, you know, I was really sick or my family member was really sick or what have you. And after this intense experience with the medical system, the last thing I wanted to do was go work in the medical system for the rest of my life. And then there are these other people who have that same kind of close scrape. And yet what it does for them is it actually catalyzes the desire to go into medicine like that's the very thing that they bring out of that kind of experience, which is just to say that having that kind of experience when you're young can cut both ways. And so I guess I'm just wondering, before we talk about the details of your medical career and what you ended up specializing in, can you just talk to us about what was it about that experience which came at a really transitional time for you, right? Like you're sort of just leaving the nest and just establishing yourself on your own, and then you have this devastating experience with someone who you love so dearly. What was it about that experience that ended up catalyzing you, then wanting to go into medicine?
David Fajgenbaum: [00:04:57] Yeah, and it's such an important question because I have friends who, as you said, gone through similar sorts of experiences and, and maybe taken a different path. For me, I think that as a freshman in college, you know, knowing my mom was sick with cancer and visiting her most weekends when I was in college, when I was at school, being able to take pre-med classes made me feel like I was like doing something directly for someone like her in the future. It was this sort of feeling that like, if I'm going to be away from home and I'm not going to be with her, like, let me make sure that the time I'm away from her is towards the service of someone like her in the future or maybe her, you know, of course I hoped that she would she would live longer than a year. And so I think for me, that's what it was. It was that if I'm going to not drop out of school to spend time with her and the rest of my family while I'm here, I want to be doing something that's sort of in her honor. And so it was very much this this connection to her. And and then I just found that I love science and medicine, too. And so I think that those things kind of combine to I could channel my energy towards something that I felt was, you know, in the service of someone like her. And I also just really, really loved the topic.
Henry Bair: [00:06:04] Thank you for sharing all of that. Can you give us a brief snapshot, if you will, of what your life looked like? What was your lifestyle like as a medical student before you came down with Castleman Disease?
David Fajgenbaum: [00:06:18] Sure. Well, I played college football at Georgetown. You know, we're not known for our football at Georgetown. But but I was a quarterback there and I was always really into fitness and exercise. And I was sort of in the best shape of my life, as healthy as one could possibly be as a third year med student at Penn. And yeah, I had never had any medical challenges myself. I had actually just won a bench pressing contest in the state of Virginia like a couple months before I became critically ill.
Tyler Johnson: [00:06:50] Just like all of your medical school classmates. I mean, all of them were clearly going around and winning bench pressing competitions as medical students are wont to do, you know?
David Fajgenbaum: [00:06:58] That's right. Well, actually, all of my friends traveled with me to this particular contest. But but yes, it was I was truly as healthy as one as one can be, frankly. And and I also was on my ob gyn rotation, which, as both of you all will remember very well, that really also feels like a pinnacle to of medical school, right, to where you're actually helping to bring life into the world. You know, you're delivering delivering babies. I mean, it's like that. That was the moment I was at when when really everything came crashing down.
Tyler Johnson: [00:07:29] I'm going to try to hold off on making comments about how I would have predicted that you were going into orthopedic surgery at the time that you won the best wrestling contest.
David Fajgenbaum: [00:07:38] You know, amazingly, despite that, I still wanted to do oncology, despite the fact that I was, you know, physically, you know, more more of a fit for orthopedics. I was going.
Tyler Johnson: [00:07:48] To ask you if you ever wore a scrub tops to anatomy lab that were 1 or 2 sizes too small. But we'll just hold.
David Fajgenbaum: [00:07:54] Never, never, never.
Henry Bair: [00:07:57] Yeah. In your book you detail your fitness regimen, and it's clear that you took this very seriously. I mean, I would probably die or at least go into rhabdomyolysis if I tried to emulate your routine. Right. Which is all to set up just how much things changed in an instant. So can you tell us what happened around the time you came down with this mysterious disease?
David Fajgenbaum: [00:08:19] Sure. So as I mentioned, I was a third year med student. I was on this ob gyn rotation and I started noticing I was feeling more tired than I'd ever felt before. But of course, we're all tired in med school, right? I noticed some lumps and bumps in my neck, which felt like enlarged lymph nodes but wasn't terribly concerned about them. Started noticing these cherry hemangiomas. These little blood moles popping up on my chest and shoulders, which I thought was unusual. But as you know, hemangiomas are normal and benign on their own. But all of these things happening simultaneously felt really concerning. But I wasn't all that sick yet. I was just sort of like seeing these things happening. And I actually turned to my med school classmates who were my roommates, and I told them, I said, I think I'm dying. And they looked at me. They're like, You've got some blood moles on your shoulders. And you, like, feel tired. You're fine, right? You know, you're fine. This is just what happens when you're a medical student.
Tyler Johnson: [00:09:15] And I was like, I feel obligated to say to all the medical students who might be listening that no, that lump you felt three weeks ago during the lymphoma block was probably not lymphoma or Castleman's disease. We just want-
David Fajgenbaum: [00:09:25] Exactly, No, exactly. And that's what my friends were all saying. They're like, No, this is what happens to every med student. Like, you know, we all get worried about stuff here on the clinic. So I actually just diagnosed a young patient my age with lymphoma. And so, like, you know, I mean, all these things. And I was like, But I anyway, so over the course of a couple of weeks, that fatigue just got worse and worse. I started getting this really bad abdominal pain, started noticing fluid around my ankles, which was just so unusual again, given how how healthy I was. And and then my appetite just went completely away. I started feeling nauseous and I just stopped eating. So those were the three days before my ob gyn shelf exam. And and so for those three days before it, I was just exhausted, night sweats. Every night I could barely stay awake. And I share this particular anecdote in the book, and that's that I would go from room to room. I would see a patient in a room, and then I would go find an empty room and I would take a nap on the on the bed in the room for seven minutes. I would set my alarm for eight minutes from the time that it was I would sleep for the seven minutes because that's how exhausted I was. My alarm would go off at eight. I would get up, I'd walk to a room, I'd go sleep somewhere else for seven minutes, get up. And so I'd take like, you know, ten, seven minute naps a day in between seeing patients. And anyway, I took my my medical school exam. And I have to admit, during it, I was just I felt so sick and I didn't know what was happening. I was confused.
David Fajgenbaum: [00:10:52] And thankfully, Penn actually never gave me my grade back for that exam. I'm sure it was like a zero or a negative score. But yeah, so the exam didn't go very well and I walked straight from the exam to the emergency department, told about my symptoms. They ran some tests and the doctor came in and said, David, your liver, your kidneys, your bone marrow, your heart and your lungs are all shutting down. We need to hospitalize you right now. And I started on dialysis. I started getting daily transfusions of platelets and red cells. I started getting albumin infusions every six hours. I mean, I literally was like I was, you know, multi-organ system failure. And that was really just the beginning of it. And I gained about 70 pounds of fluid because my liver and my kidneys weren't working. And I had a retinal hemorrhage that made me temporarily blind in my left eye and all with no diagnosis. It was just weeks and weeks of critical condition out of it for nearly the whole day. And I would wake up for, you know, maybe an hour or so, and no one knew what it was. And the concern, you know, is it a lymphoma, was it some sort of infectious disease, is some unusual autoimmune disease. But every group that would come in to see me, every consult service would be like, it's kind of like autoimmunity, but it's not us. Talk to oncology, oncology. It's kind of like oncology. It's not us talked ID and so they sort of all said it's kind of but not us and, and that kind of circle or wagon or whatever you want to call it sort of went around and around for weeks while I was, you know, literally teetering on the brink of death.
Tyler Johnson: [00:12:27] I just want to make clear. I am not in any way making light of your experience. And yet at the same time, I feel like we really have to send out a preemptive apology to all of the emergency room doctors who are going to be feeling all of the poor medical students who come in convinced that they're in multisystem organ failure because they found some like red spot on their chest or whatever. Over the next couple of weeks, I just want to say right now, we're sorry.
David Fajgenbaum: [00:12:50] You know, I think finding humor in the midst of these things is really, really important. And I and I also think that warning is is, well, well deserved.
Tyler Johnson: [00:12:59] So let me try to transition. You know, we've kind of been having fun a little bit making light of this a little bit. But let me try to transition from treating this lightly to then a really serious point and a serious question. You know, I remember back when I took my cardiology block at Penn with Dr. Hirschfeld as the course director. I still remember the day that we had our lecture on cardiomyopathy, which of course, was a word I hadn't even heard the word before, let alone know what it was or what it meant. But I remember having the lecture that day and, you know, we sat in lecture for four hours and listened to what a cardiomyopathy is and what causes it and what it does to the body. And et cetera. Et cetera. And then I go that afternoon and I study it all afternoon. And I still remember going home that night and lying down on the bed. And I'm lying there on my back. And suddenly, for the first time, at least that I can remember was aware of in my life, I could feel my pulse in my neck. Like every time my heart beat, I could feel the pulse. And I just remember this sort of eerie recognition washing over me like, oh my gosh, I have this beating thing in my chest. That was the first part. And then the second part was. Oh, my gosh. Is this what cardiomyopathy feels like? Like maybe this is what it means? Like, I knew that it was going to happen sometime, and it happened the very night of the cardiomyopathy lecture. What, you know, terrible luck. And of course, you know, you guys are both laughing at this because it's sort of funny to think back on it. But in real time, it felt, you know, pardon the pun, but it felt deadly serious.
Tyler Johnson: [00:14:38] Right. Like I really thought that something was wrong. So then and this is, I think, an experience that every medical student has, right? Like you sprain your ankle and it gets swollen and you're convinced you're in liver failure because your leg is swollen or whatever. Right? Like sometimes it's just completely absurd. But the thing is that for all of the absurdity and for all of the times that that has happened to medical students here, you have some, you know, whatever, a little bit of a fever and a red spot on your chest and some stuff which, you know, 999 times out of a thousand would be absolutely nothing. It's some, you know, influenza or upper respiratory virus or whatever. And you go into the emergency room and you are in multi-organ failure. Your liver is failing and your heart and your kidneys and whatever. And within hours or days or whatever it is, you're in the ICU and now you have, you know, these people who have or many days ago were your medical school professors, and they're coming in and they're consulting on you. And not only are you in multisystem organ failure, but these, you know, erudite professors at one of the best medical schools in the country, don't even know what the heck is going wrong. So all of that is to say, hey, on the one hand, this is, you know, every medical student's worst nightmare. But on the other hand, what was it like to be you to be like inside your heart and mind in that moment when now all the tests are coming back and whatever and all of that stuff that most of us absurdly fear might be going wrong actually was.
David Fajgenbaum: [00:16:03] It was terrifying. I mean, I think that part of why it was so scary was that in medical school, every professor and everyone you engage with seems like they have an answer to everything, right? Because, like, frankly, you know, the questions that you ask on medical school exams are questions that you have an answer to, right? There's never like what, you know, treats this disease. Oh, no one knows like that. Like, you know, that's not part of medical school. Like there's there's an answer for everything. And every attending you ever engage with has an answer for it. You're like, Oh, like this is great. Like, if I get sick, like they're going to have an answer for me. And all of a sudden, like all of those people who had every answer for me, like when I was a medical student as their student, they had no answers for me as a patient. And I was like, Oh my gosh, this is this is crazy. So it was it was terrifying because both I was literally like actively dying. I had seen I had seen the labs that I had in the ICU, and those people didn't survive like so, so, so that was frightening. And then the other thing that was frightening was that all the doctors that I had ever seen come up with answers because they were all coming to visit me, right? Like, you know, all of my my favorite attendings, they were, you know, trying to come in and, you know, come up with an idea. None of them had any any ideas. None of them had certainly didn't have the right ones. And so it was both frightening objectively, but also it was just frightening from like the sort of the, oh, my gosh, how could this be right? You know, the system that's here to help all patients. But but I think especially a medical student, you know, really was was struggling to come up with answers for me.
Tyler Johnson: [00:17:35] So I know this next question is going to get a little bit personal. And, you know, obviously you can share however far you feel comfortable in answering the question. But I'm just so struck that on the one hand, you know, here you are just before you come into medical school and then and then as you're beginning medical school, you are like the quintessential athlete, right? You're playing college quarterback and then you're literally winning weightlifting competitions and you're doing the weightlifting competitions while you're making your way through medical school. And I just have to imagine that you, of all people, it must have seemed that you were invincible in a way that you probably never even thought about. That's the thing about having a default of invincibility, right, is that you don't ever have to consider it. It just is the state of affairs. It's like you wouldn't even it wouldn't even occur to you to think about the possibility that something could really happen to you because you were at your peak. Fitness, right? You're out there throwing touchdowns and lifting dumbbells and going back and forth from medical school to weightlifting and sports and whatever. And you must have felt, even if you never thought about it, invincible, And then all of a sudden, within a course of days, weeks, months, depending on how you want to draw your start and finish time, you are in the ICU in multisystem organ failure as far as you could tell or any of the doctors could tell, basically staring death in the face and thinking, Oh my gosh, I might never leave the ICU. So I guess I just am wondering, what do you like, what does a 20 something weightlifting college quarterback do? Like mentally, emotionally, metaphysically, when you are suddenly confronted with your own mortality in such a stark and abrupt way?
David Fajgenbaum: [00:19:29] Yeah. So it was difficult. And I mean, difficult is the ultimate understatement that it was difficult. No, it was incredibly difficult. And I mean, I think that a couple of things that come to mind. One is that in my case, because I had watched my mom's battle with cancer just a few years before and I had seen the way it broke down, someone that in my mind was invincible. And to see the way cancer broke her down and the way she stayed resilient and gritty and amazing and powerful, despite the fact that she died from cancer, I think that that helped me in a lot of ways. I didn't have to fight with this sort of as much. I mean, I certainly fought in my brain around like, why me? But I didn't fight with that as much because I had both seen what can happen to to someone that doesn't deserve something. And of course, in medicine, you see that happen all the time. No one deserves illness, of course. So I think that some of that my brain had started to wrap around a little bit that like, you know, life's really unfair, which which maybe helped in some ways. I think part of it also, having seen the way my mom sort of graciously handled this, I think helped me in some ways.
David Fajgenbaum: [00:20:40] It is the understatement to say that it was difficult. All those things just helped me a little bit and it still was really, really, really tough. And I spent a lot of time in the ICU crying and I spent a lot of time, you know, grieving the life that I wanted to have. I wanted to make a difference against cancer. I wanted to have a family with my girlfriend at the time, Caitlin. I wanted to do so many things that I knew I would never be able to do. And frankly, just watching, you know, nurses and doctors walk into the room, it was like, oh my gosh, like, imagine if I could walk. Like, wouldn't that be amazing? Because because I didn't walk for weeks and weeks, I was completely hospital bound and I wasn't able to walk sitting up, you know, setting my heart rate through the roof. And and I felt unwell just sitting up in bed. And so, like, little things like that, I just I remember seeing them walk. I'm like, wow. Like, I would love to walk. And so, yes, it was it was really, really difficult. Right? And of course, if you can contrast that to a few months before when I was like, you know, the physical state of health we're walking was like, you know, an afterthought.
Henry Bair: [00:21:47] Yeah. So as you mentioned in the ICU during that first bout of this this disease, no one knew what was going on, but they gave you high dose steroids, which happens to a lot of.
David Fajgenbaum: [00:21:59] You should always do. Anyone listening always try to steroids before you give up.
Henry Bair: [00:22:03] It's just it's interesting because literally today in the hospital, there was a patient on our service who who's who has metastatic melanoma getting immunotherapy. And she comes in with like this gastroenteritis picture. We don't know what's happening. Is it immunotherapy? Is it like cancer related inflammation? Is it infection? Just slam her with a lot of steroids and she's getting better. So just I read your book last week. I was like, oh, yeah, I remember that. So So you do get better, right? Like, mysteriously you still don't know what's happening. But for a moment there, you do get better. So it's almost like now you have a second chance, right? What was going on in your mind?
Tyler Johnson: [00:22:41] So I'm sorry to interject here just for a second, David, before you answer Henry's question, but I just have to say that on the one hand, for those who are maybe not as far in their medical training, I just want to point out that in the first place, it is so unusual for a young, healthy person with no discernible medical problem to just show up to the emergency room and then end up within a day or whatever in the ICU in multisystem organ failure for a reason that nobody can even pin down. Like that's very unusual. But then what is unheard of is that that same person who only gets some basically nonspecific medical treatment, like we're joking about, you know, everybody should get a dose of steroids, like get some nonspecific medical treatment. Nobody knows what's going on. And then, poof, you just get better. Like that never happens. I mean, I'm not a critical care doctor, but I have taken care of a lot of patients in the ICU, both during my training generally and then oncology patients as an oncologist. And I cannot remember ever seeing a case like that. So I think it's just worth highlighting how exceptionally unusual that is.
David Fajgenbaum: [00:23:45] Exactly. And one of them I mean, I remember asking this ICU doctor when I started spontaneously getting better, it was like, you know, is it going to come back? Because we didn't know what it was. It was just it. Right. And and he said, well, if it's bad, it's going to come back and and I'm worried it will. And and so for me, even though like my health was coming back, my brain was still very much on like, what was that like? Let's try to figure that out before it comes back. And so, yeah, I was I was out of the hospital for about four weeks and I spent nearly all of those four weeks. I started requesting my medical records from like when I was a kid. I was getting like my vaccination records. I mean, I was totally healthy kid, but like, I was trying to find something, anything. And I went through, you know, going through all my records at like thousands of pages from because I spent seven weeks in ICU. And so like seven weeks in ICU, you get a lot, a lot, a lot of tests to run. And so, yeah, I mean, the next four weeks were fully like going through records, going through childhood records and, and trying to figure out what it was. And then it came back.
Henry Bair: [00:24:47] So then this kind of happened several times, right? You go in and out of the ICU, you get better, you get worse. Mysteriously, people try different medications. And then at some point you say, enough, I'm going to try to sit in the driver's seat for once. And then you start poring over your own lab work, all the medical records that have accumulated throughout your hospitalizations, you start trying to figure out whether there are any experts who might know something about whatever is happening. Yeah. Can you tell us more about that process of switching from being a passive to an active participant of your own care?
Tyler Johnson: [00:25:23] As you're answering that question? One thing that I'd love for you to talk about specifically, you know, I can't help but put myself in the place of the professors that you had in medical school who are taking care of you in the hospital. Right? Like, I can only imagine if I were like if one of the students that I know and love here at Stanford were to get this sick and end up in the ICU and nobody knows what's going wrong and whatever, like I can only imagine the just almost insatiable desire that I would have to figure out what's going wrong. But but and you know how to fix it. But one of the things that, again, for people who are younger in their medical training that you may not really have an appreciation for yet, is that when you're in the process and when somebody is in the hospital and they're really sick and you're trying to figure out how to make them better, almost always the first step is to say, what category of disease is this like? What kind of expert do we need to talk to? And I can only imagine that one of the things that must have been so galling for the people who were taking care of you is that they didn't even know the answer to that question. Right? Like not only did they not know, it's not like they knew you had lymphoma, but they weren't sure like which really exotic subtype of lymphoma. They didn't even know if you had a cancer or an infection or a rheumatologic like autoimmune, like they didn't know any of those things. And I can only imagine that. That inability to even categorize what was going wrong must have been hugely, hugely frustrating.
David Fajgenbaum: [00:26:55] Exactly. And each person I try to go to, you know, you could come in and room would come in. They would say, it's not us, it's the other one. And so we're like, Well, everyone, you know, thinks it's the other one. So it's like, you know what's happening here. But I think that it's such an important question around moving from I had a major evolution over the course of my illness, and certainly it started early on, and that was this evolution from being a patient, you know, a reluctant patient. Obviously, I certainly didn't want to be there. No patient wants to be a patient, but went from being just a patient to sort of with every sign that the medical system wasn't going to solve it. For me to saying, okay, I want to do a little bit more to get like more into the driver's seat. Like, you know, I'd rather just sit in the back, like, you know, let the system take care of me. But but every time, you know, the system couldn't figure it out, it's like, well, all right. Well, that was sort of, you know, this evolution towards wanting to wanting to move forward. And of course, at the end, as you know, I got really involved in my care. But so in the early days, it was yes, it was looking through those medical records, I actually encouraged my doctors to finally do a lymph node biopsy, which is after 11 weeks, what actually led to the diagnosis.
David Fajgenbaum: [00:28:10] So it was this lymph node biopsy that they did because of concern for lymphoma, but it came back that it wasn't lymphoma, it came back that it's something called idiopathic multicentric castleman disease. And so for our, you know, folks that are earlier on in their careers, any disease that starts with idiopathic isn't good because that means we don't know the cause of it. It's our fancy, fancy word for like we don't know what the hell is happening. And so I have idiopathic multicentric castleman's. So that means it's basically it's a cytokine storm disorder where your immune system attacks and shuts down your vital organs for an unknown cause. So we don't know the etiology, but we do know that at least for a large portion of us, that one particular cytokine called interleukin six is really the driver. It like it really drives this whole cytokine storm. And so with the diagnosis, what was exciting at the time was that that should come with treatment, right? And so I got transferred to actually down to to North Carolina, which is where my family lives. And so I ended up going to Duke. And at Duke, the Duke doctors were not aware of the sort of standard of care which is IL six blockade, but they gave me rituximab which can be used in some cases, typically further down in terms of lines of therapy.
David Fajgenbaum: [00:29:22] I was so sick by the time that I got to Duke and started getting Rituximab that my doctors told my family that this was it and that I wasn't going to make it. And a priest came into my room and read me my last rites. So that was November of 2010. Said goodbye to my family. I don't obviously don't remember it. I was very sick but said goodbye to my family. A priest read me my last rites and the treatment was started and thankfully the treatment worked enough to get me out of the hospital. About a month later, I spent another month in the hospital, but now I had a disease that was somewhat responding to this treatment. I had a name for it, and so now I wanted to figure out, well, who's the expert for this? I found out that the world's experts in Little Rock, Arkansas, and now I was at Penn for medical school. I had spent time now at Duke. And all of a sudden I learned that the the epicenter for Castleman Disease in Little Rock, Arkansas. So I flew to Little Rock with my dad while I was out there seeing the world's expert, I had another relapse and all of my organs started shutting down again, hospitalized me. The lab values are just insane. What what my my immune system would do to my body.
Tyler Johnson: [00:30:30] Can you just give us an idea for those who are well versed enough in what the different lab values mean? Can you just give us a sense of what some of them are?
David Fajgenbaum: [00:30:38] BUN of 224, BUN of 224. I mean, I've never seen over 100, right? I mean, like 224. A CRP of 350. Like again, CRP normal is up to 10. Thirty times the upper limits of normal CRP. I've never seen that before. And all I do is study hyper-inflammatory diseases, by the way. So like and so so these are these are values that you just don't see ever. And they were happening and they were like, you know, they were right in front of my face and needed dialysis three times a week. Of course, needed, you know, daily transfusions. They tried IL six blockade. So the only drug that was in development for Castleman's targets interleukin six, there's a clinical trial going on of it. There's also an IL six receptor blocker that had been used somewhat off label at the time. But I got the I got the drug through this trial and we hope that it was going to work. It was sort of like, this is amazing. Like this is the drug that's supposed to work for everyone. And it didn't work for me. I kept getting worse and worse despite IL six blockade. So I ended up getting a combination of seven chemotherapies Adriamycin, Cytoxan, Etoposide, Velcade, Dex, thalidomide, Rituxan. And that combination of seven chemos just completely obliterated my immune system. And I actually felt better with every dose of that stuff. And anyone listening who knows anything about Adriamycin, Cytoxan or Etoposide knows that they're like the worst chemo's out there. But I was so sick before the chemo that actually I felt better with it because it was actually controlling this disease that was literally killing me.
David Fajgenbaum: [00:32:11] And so chemo got me out of the hospital. I spent another seven weeks hospitalized. Chemo got me out of the hospital, and I went back on this experimental drug, the IL six blocker, with the hope that maybe it could keep me in remission, but I really. Well, not no buts to that. I really hope that it would keep me in remission even though it didn't help me in the acute phase and spent about six months recovering back home and then returned to medical school at Penn, got another six months of rotations under my belt, kept getting this IL six blocker and then I relapsed on the blocker. That was devastating. I mean, that like to be on the drug that like, you're like, this is going to keep me in remission. It may not have worked when I was sick, but I was too sick. You can sort of like handwave that there was too much IL 6 and so we couldn't control it. But now it was like I was on it for a year and I had a full blown relapse. I spent another month in the ICU. Don't know how I survived, but somehow survived thanks to a combination of chemotherapy. But this for me was like the ultimate moment where I was like, okay, I have to go. I have to move from the world where I hope that my doctors figure something out for me to a world where, like, my doctors are fully out of options.
David Fajgenbaum: [00:33:20] Like my doctor told me that he's like, this was it like, we don't have anything else? We've got no more leads. We have no more targets. Like, we're just going to keep giving you chemo. And one of these days it's not going to work. And so this is so we're sort of out. And so and that's when I turned to my dad and my sisters and my girlfriend at the time, and I said, I'm going to dedicate the rest of my life, however long that may be probably going to be measured in weeks, maybe months. But I'll spend the rest of the time I have trying to find something to treat my disease. And and two really important comments about that. One is that I knew the only way that I could make any difference for me or for anyone else would be to find an existing drug that we could repurpose for castleman's. And so both of you all very well aware of this, and I'm sure many listeners are, but there are about 3000 drugs that are approved by the FDA, and many of those drugs have activity for other diseases that they're not approved for. But maybe because the drug is generic or maybe because there just hasn't been research done into it, work hasn't been done to fully unlock the potential of drugs. I didn't really know that at the time, but I did know that the seven chemotherapies that had saved my life four times were not made for my disease.
David Fajgenbaum: [00:34:29] And I'm like, Wait a minute. If those drugs weren't made for my disease and they saved my life, like maybe there's some other drug that's not made for my disease that could save my life. And so and I knew it was my only chance, right? I didn't have $1 billion. I didn't have ten years to develop a new drug from scratch. So, like, if you want to survive, you know, you sort of have to like MacGyver it, right? You got to use the things that are within reach. I don't know if MacGyver might not be a reference that that some of the newer medical students will have. But MacGyver likes to solve things with, you know, things within reach. Right? So that was one part. The second part was that we couldn't really follow the traditional approach to medical research where you raise money and then you invite researchers to apply or apply for your funding and you pick the best ideas. We really needed, in my opinion, to crowdsource from the whole community physicians, researchers and patients to figure out what should be done and then go actually recruit the best people into our community. And I felt very strongly about that because Castleman's has been described since 1954 and we had like one drug target. So we had to do something a little different in my opinion. So we so we did we started a foundation to do things differently. And I started doing work in the lab at Penn. It was a it was a pulmonology lab that had never done castleman's work before.
David Fajgenbaum: [00:35:34] I hadn't ever done basic science research before. So it was a lot of a lot of novices, you know, working with novices. But again, it was like, okay, you know, if we want a chance at this, let's do it. So started storing samples on myself in the lab in case I relapsed. And I and I did relapse about a year later. But this time I now had blood samples that I had stored every couple of weeks leading up to the relapse. So got the same seven chemotherapies. And when I got out of the hospital, went back to the lab and did a bunch of experiments, did cytokine panels, flow cytometry, serum proteomics. And over the course of about three weeks, I honed in on this really strong mTOR signature in my blood. And I had asked for a lymph node to be resected during my last relapse. And so I asked for it because if I got out, I wanted to have some tissue to work with. And again, I mentioned this sort of evolution of like action. Like I would have loved to not be my own guinea pig. I would have loved to be like medical system, like, give me what you got. Like, you know, tune me up and let me go. But like, over and over and over again, that didn't work. And so it got to this point where I was like, okay, like, if that's not going to work, then like, I guess I got to be my own guinea pig.
Tyler Johnson: [00:36:42] I just have to like, hearing you tell this story makes me think of an analogy that we often use in medicine, which maybe is not the best analogy, but after all, you are a quarterback. So it seems at least apropos here, which is that, you know, we often if we have a person who's really, really sick and we've tried a bunch of stuff and nothing is really working and we wish that they were getting better, but they just aren't. We'll often use the analogy of a Hail Mary pass, right? That it's like, well, you know, we just want to heave the ball downfield and we'll do basically anything to try to get them better. But the thing that is different in your case at this point in the story from those cases is that now you know what the disease is. You even know to some degree, at least in many cases, sort of how your how the disease is mediated. And you have a therapy that is supposed to block that very chemical. That is the mediating thing for many cases of this disease. And so if you think about it like that, the Hail Mary analogy almost doesn't feel apropos anymore because usually if you talk about a Hail Mary pass, right, you're talking about like a scrum of 15 people who are down the field and the quarterback just sort of throws it in hopes.
Tyler Johnson: [00:37:44] Is that one of their people jumps up and gets it. But this feels almost more like you have your favorite receiver wide open downfield ten yards from the end zone and you throw it and they just sort of look at it and turn around and walk away without catching it and like, which is just to say that I can only imagine that, you know, once you think you know what's going wrong and what you think, that you've found a therapy that might work to really help to be in that head and heart space and then have the to mix our metaphors, have the rug yanked out from under you Like that just had to be so devastatingly dispiriting. Like, I can only imagine what it must have felt like when it didn't work. And then it seemed like maybe it did in the outpatient setting, but it didn't in the inpatient setting. And I that that just has to have been such a roller coaster of emotions.
David Fajgenbaum: [00:38:32] Exactly. And it's not that I want to find a receiver. I have to write. It's this sort of feeling that like, oh, my gosh. And so it was sort of yes, you're exactly right. And and so here I was now, I had a signature that I thought mTOR is key signaling pathway. It's basically a communication line in the immune system that immune cells use to communicate and engage with one another. I thought it was turned on, went to that lymph node that I had had resected my my doctor. When I said, I said, Do you think you can take a lymph node out of me so I can have it for research? And he said, Do you want fries with that order? Because he was like giving me a hard time because I'm like, because I'm like ordering him to, you know, cut out one of my lymph nodes. He says, Do you want fries with that order? I said, No, I just want my lymph node out. So here we are. I could get that lymph node that I did not get fries with, but I have the lymph node now and I was able to to do a really simple experiment where basically I tested the tissue to see how much was the mTOR pathway turned on or not, and it came back blazingly positive. And it was this moment of like excitement, euphoria. And the reason it was so exciting for for those listening is that there are mTOR inhibitors that exist that have been around for decades and they're really good at inhibiting mTOR. And of course there's no guarantees in medicine, right? Like you can find out something's up and you try an inhibitor and doesn't work. But, but I didn't have any other options. And so I shared the data with one of my doctors. And yeah, he, he said, you know, he said, David, it's probably not going to work, but we've got no other options. And it's a cheap generic old drug with a really well established safety profile. Like, Sure.
Henry Bair: [00:40:12] Is this a everolimus or.
David Fajgenbaum: [00:40:14] It's sirolimus, it's the drug before everolimus. So it's like the it's the old one. It's like the original, you know, the original mTOR inhibitor. And and we could have gone with Everolimus, but I felt like, let's go with the old one with the nice long track record of safety. And so we started me on it and I was still recovering from the hospital. And July 5th of this year marks nine and a half years that I've been doing great on this drug. My longest remission before that was about one year. We've now looked at mTOR signaling across hundreds of patients and it is uniformly elevated in Castleman disease, which has been both really exciting but also frustrating because it turns out though mTOR is up across all of us, blocking mTOR only works in about 20 to 25% of us. So we continue to fight for more and more treatments. But I think one big takeaway that I will share at this moment is that. Every time I walk past a CVS. Even today, when I walked past the CVS, all I can think about is how many drugs are in that CVS that could actually be life saving for another disease. But we just haven't figured it out yet that our system just hasn't yet turned the wheels, done the tests, figured out what else can sirolimus be used for what else can you-name-it drug be used for? And so that's what I am like totally fully obsessed with right now, is how do we unlock the full potential of drugs?
Henry Bair: [00:41:46] This is such a ridiculously inspiring story. I mean, I can we optioned the movie rights?
David Fajgenbaum: [00:41:51] There's there's Wendy Finerman. She did Forrest Gump. She's working on trying to make a movie out of this. So we'll we'll see if that ever happens. There's some strikes going on right now, but but Wendy's trying to make it into a movie.
Henry Bair: [00:42:02] Well, I will be first in line to buy that movie ticket. Okay. Right. So so now you have this burning desire to not just help other people with Castleman disease, but also apply the same principles you've used to discover your own cure on other rare diseases that currently have no treatments. Can you tell us more about the initiatives you have spearheaded in this regard?
David Fajgenbaum: [00:42:28] Sure. So after medical school, I did an MBA at Wharton right afterwards, and that actually while I was doing this lab work, it was while I was in business school. And the reason for that was that I realized that a big part of solving disease is bringing together communities, utilizing resources efficiently, building teams, that sort of stuff. So I wanted to do my MBA, but it also meant that I would have time to work in the lab. And frankly, if I had done a residency instead of doing an MBA at that time, I would have never had all that time to do deep immune profiling and I probably wouldn't be alive. I'm not telling any listeners to not go to residency because it's life or death, but I'm just saying in my case, it actually it actually was life or death. But so I finished business school and then I joined the faculty right from business school at Penn to set up a lab. And the reason I was able to do that is because I had demonstrated a bit of a track record from my own case. But I also received some funding to set up this lab and to set up a program. And and the school believed in me.
Tyler Johnson: [00:43:28] And just to be clear, by a bit of a track record, we mean that you made your own diagnosis that none of the professors at the School of Medicine could make then figured out the cellular pathway that was mediating it, then figured out a medicine that already existed that could be used for the cellular pathway and in effect cured yourself. So yeah, guess we can call that a little bit of a drag.
David Fajgenbaum: [00:43:47] Well, thank you. You're making me blush for anyone who's listening. I'm fully blushing, but. But yeah. So joined the faculty from the MBA and started building a center called the Center for Cytokine Storm Treatment and Laboratory, where we do deep profiling of cytokine storm or hyper inflammatory disorders. And then we ask the question, what drugs are already FDA approved that can address these disorders? Since then, we have now identified 16 drugs that can be utilized for diseases they weren't initially intended for all in the hyper inflammatory disease space, which has been like the ultimate experience of my life, right? I mean, patients come to our center. They have a disease where there isn't necessarily a drug, or maybe there is a drug for their disease, but it didn't work for them. We find another drug for them and they go and they don't. They can sit in the in the back of the car. They don't have to worry about driving the car. They can just, you know, go back to their lives, which is just amazing. So that's what I've been doing for the last nine and a half years. But then a year ago, I set up a new organization called Every Cure.
David Fajgenbaum: [00:44:45] And Every Cure was really inspired by the fact that, wait a minute, we've done this a total of 16 times within rare hyper inflammatory diseases. What about all the other diseases and all the other drugs out there? Can we do this in a high throughput way? Can we look across drugs and diseases to make matches? At the end of the day, all it is, is matching drug X to disease Y, And can we utilize artificial intelligence in the world's biomedical knowledge to help us to predict what drugs might treat, what diseases, and then can we move them forward into trials in cases where drug companies aren't interested and over 80% of drugs are generic. So for over 80% of all drugs, there is no commercial interest to pursue new uses for them. So we started a nonprofit about a year ago and it has been so exciting to be able to really dig into the most cutting edge data science around. How do you make predictions around drugs for diseases? It feels like it's all coming together and it's just been amazing.
Henry Bair: [00:45:40] Yeah, I just still find it so hard to wrap my mind around how much you have recovered from when this disease was at its worst. Now, of course, our our listeners can't really see you right now, but I would encourage them to pick up your book, if only just look at the pictures you have in them. Like you have a picture of when you were a college athlete and then when you were in the ICU with with all the assets and with all the muscle wasting. And then now back to your baseline of fantastic physical health. It's just that journey is so, so incredible.
David Fajgenbaum: [00:46:15] Well, thank you. You know, when I spent all that time in the ICU collectively, you know, first it was six months, but collectively close to a year, hospitalized in intensive care. I didn't lay there thinking, like when I get out, like it's going to be great. And my doctors weren't like, you're going to beat this. It was like, this is it. And five times like, this was it. And and the idea that I'm sitting here with the two of you and we're talking about like other patients that have benefited from these drugs and I feel great. And I didn't even tell you, but I've got two beautiful kids that are like, you know, just down the hall and and that girl that I wanted to get married to, I got married to her. It's like it just it's it's just a dream. And I'm like, certain that someone's going to wake me up. But but for now, I'm, like, loving the dream.
Tyler Johnson: [00:47:03] So, you know, I just have to comment that we're sitting here, even though the podcast is only audio. We're sitting here on a video chat, and as we've been talking, I've been looking at your background and I see all of these things, right? Like there's what looks like a framed wedding photo, and then there's a picture of what I imagine are your two kids. And then up on the wall there's like a whiteboard with project, what I imagine are projects in process. And then there's like a frame or a framed copy of the cover of your book and, you know, and then some awards and diplomas and whatever, and all of which is just to say that I have to imagine that probably the first time you certainly the first time you got sick and maybe even the last time you got sick, I don't know if any of those things like as far as I know, you weren't married, you didn't have children, you hadn't written a book yet. Like, I mean, all of these things. And here you were deathly ill multiple times. Nobody knew what was going wrong. And yet not only did you get, you know, kind of better, but you got so much better that you've then gone on to accomplish all of these things. And as I understand, I think now we're just awarded tenure at Penn. And that also then leads me to think, you know, there's this great term if you've read the Harry Potter books at the in the seventh book, when they're trying to get the Harry's first snitch that he caught to open so that it can reveal to them the resurrection stone. There's this great term that they talk about then, which is that they say snitches have "flesh memory."
Tyler Johnson: [00:48:28] And I just have to imagine that even with this, I can't think of a better word. But this miraculous recovery and all that's happened since then. I have to imagine that every time a patient comes to your center with a with a disease that nobody else can diagnose, and that is making them at least very ill and sometimes is probably threatening their life, that when they come to you, you don't just have like an intellectual sort of appreciation for the fact that they're really sick. But you must have flesh memory. I mean, I have to imagine that you have this sort of twinge of remembering what it's like to have a catheter in every orifice or what it's like to have, you know, a dialysis line in your neck or what it's like to be unconscious for days on end or to have people drawing your labs at four in the morning or whatever the thing is. And I guess I'm just wondering, because I have to imagine that that comes to you every time you experience this. See one of these patients? How how does that strike you? Like, is that part of what what spurs you on to do the important work that you're doing? Or does it hit you mostly as a burden? Like I have to imagine whatever it is, it's got to be a lot.
David Fajgenbaum: [00:49:39] Yeah, no, you're absolutely right. So there's this. There's this deep connection that obviously I feel for each one of these patients that's in the same shoes that I was in. It's like it's true empathy because it's like, I know I actually really do know what you're going through. And, you know, with every one of the patients that we've been able to help, it's been like the most exciting thing ever because I can sort of like, you know, feel what it was like for them. I can feel what it's like for their family. I can, like, see, I know what it's been like with my family. And then, of course, you can imagine the flip side is the devastation, right. When when we can't help these families and and and unfortunately, we can't help help. And we haven't been able to help all the families that have come to us. And so it's this constant like high of excitement and low of devastation that somehow creates this forward moving momentum where it's like, you know, the high gets you going to push further and the low pushes you forward as well.
David Fajgenbaum: [00:50:38] And it's sort of always moving us forward. But it's it's tough. It's definitely emotionally draining. I was giving a talk a couple days ago for a pediatrics department in Florida at a virtual talk. And at the end of the talk, I was like, man, these these last ten years, a lot's happened. It was like, this is tiring. Just just sharing about all the things that we've done these last ten years. And so it's been, it's been busy. And I think the tiring part is also there's also been a lot of highs and lows and it is hard to sustain. But it it feels like what has to be done. I mean, I just think when I think about unlocking the full potential of drugs, it's like I am not supposed to be here. And if we hadn't unlocked this drug for me, I wouldn't be here. It's like, how many other people aren't here right now because we haven't found that drug yet. And so it's just a it's a total focus. But yeah, to answer your question, it's definitely, definitely challenging.
Henry Bair: [00:51:37] So I'd like to invite you to share some advice for future clinicians. In the first question I have is, I imagine one of the most frustrating aspects of your multiple ICU stays is just how baffled everyone was. No one seemed to have the right answer, not even the best doctors in the hospital. So I'm wondering, in the midst of all of this. What stood out to you as things that certain clinicians did that nevertheless made you feel cared for and particularly comforted?
David Fajgenbaum: [00:52:11] Yeah. I mean, I think that the first thing that really made me feel better, which is separate from my clinician, but just, just what made me feel better in those tough times was my family and my friends around me. I mean, I think that in medicine, sometimes we we just see the patient and we sort of sometimes forget about the parents and the siblings and the friends and like, you know, it's almost overwhelming as a physician, if you have to sort of like mentally capture all of those people in terms of your care for your patient. But for me that having my dad and my sisters, Caitlin, by my side, undoubtedly helped me to keep breathing despite the pain and undoubtedly helped me to really keep fighting for survival. And so I guess it's not so much that that was something that a doctor did, but it was something that I realized by my doctors engaging with my family and including them in the process. Some of them did that really, really well. And that meant so much to me because I wasn't mentally able to think about anything but knowing that my family was there and that they were included and that my doctors included my family in decision making and thinking about what to do. So I think that that's one thing I would say is just, you know, some of my favorite doctors, they really engaged my family and included them in the process. And I think that was that was really special for me.
Henry Bair: [00:53:25] All right. Yeah, that's absolutely something that I'm already noticing in terms of doctors who do well, as you mentioned, in engaging, incorporating, inviting the family to participate. My second question is about research. You are kind of an outlier in how successful you have been in a short amount of time in finding a cure for this disease that people didn't really know that much about. So what advice do you have for medical trainees and current clinicians who are interested in not only practicing medicine within the scope of what is known, but actually push the boundaries of that frontier?
David Fajgenbaum: [00:54:04] Yeah, it's such a great question because when I first went into medicine, I really envisioned my career being primarily patient care and maybe being involved in research, maybe in clinical trials or sort of dabbling in research. And then I really fell in love with it. I mean, obviously I sort of had to fall in love with it at first, right? Because I needed to do it first. But I truly fell in love with it. And, you know, the pursuit of answers to questions that the world doesn't know yet like that gets me so excited, you know, into into really, as you said, you know, push, push the frontier. It's really, really fun. And so I guess in terms of anyone who's interested in research, I think what I would encourage you to do is to really look for those areas that get you really excited because I have a lot of colleagues who sort of do research to check a box and like to, you know, to get X number of publications a year because that's like part of their position. And, and then I have other friends who, like are really, really, really excited about what they're doing. And I think I fall into that category too. And I think that it's, it's so important to find it. It's just about it's just matching, you know, all of us have different interests. We have different kinds of research that would be a good fit for us with different kinds of diseases, different kinds of drugs. But so don't sort of settle for that first opportunity because like your mentor studies that disease and it's great to have mentors who study the same disease.
David Fajgenbaum: [00:55:21] You but but really keep searching for the thing that gets you really excited. And if you can't find it after a long period of time, that just might tell you that research isn't what you're interested in and that's fine. But I think that really strive for the thing that gets you excited. And and again, research is like we think about it as like one thing, but there's like a million ways to conduct research. So I think continuing to search for that thing you get really excited about. And I've also found from a grant perspective that a lot of my colleagues will submit grants for federal funding based on like where they are in their career. And it's like, you know, well, this is what I need to do. I need to submit an R one because it's been this many years into my career. And I think that that's a mistake. I think that it really should be around the maturity of the data and and the importance of the question. And really, because I do think study sections and people who give out grants, they can tell the difference between a grant that's like, well, I need to get an R one so I can get tenure versus like, this is something that could really help a lot of people. And so I think just really try to focus your science on, on on the science and on the impact. And it's hard to do, but try to try to dissect it away from career development.
Henry Bair: [00:56:32] So I know I said I had two questions, but actually a third just came to my mind that I would really love to ask. Going back to why Tyler and I started this podcast in the first place, we did so initially to try to answer the question Why is there so much burnout in medicine today? And along the way we discovered that there actually are certain practices and mindsets that individual clinicians can adopt to elevate the human connection at the heart of doctoring and in doing so come in touch with the transcendental, metaphysical or whatever else you want to call it, the sacred dimension that makes this work so meaningful. You are among only very few people with interviewed who have been on both the dispensing end and the receiving end of those sacred encounters. Not just once but over and over again with your trips to the ICU. What have you learned about that place? Those encounters that you can share with the rest of us?
David Fajgenbaum: [00:57:37] Probably the first thing I would say is. Is it's about spending time and being present with that person on the other side with you. I think that we're often in medicine, we're so busy and we're pulled between 15 different patients who are struggling in the ICU. And so we just can't spend that much time. The experiences I had as a patient and then I think also the experience I've now had on the other side where I'm giving our most precious resource, which is time. And like you said earlier, when we're young, we don't think time is a precious resource. But when you have your last rights read to you, time becomes a really precious resource, right? You know, I think time is just, you know, it's about being present with your patient. It's about when you're giving that time with them to sit with them, to listen to them, to to, you know, to be present with them and also to to think with them. You know, I think that, you know, we didn't have time to go into this in depth, but those blood moles that that no one was worried about early on and that I shouldn't have been worried about, it turns out that they're actually a really good biomarker for how you're responding to therapy in Castleman's because vascular endothelial growth factor is increased when our disease is active and mTOR is driving the VEGF.
David Fajgenbaum: [00:58:56] And so those blood moles actually were giving us a sign from day one that there was increased mTOR signaling in my body. And again, my doctors should not have been focused on that. But like that's the kind of thing that it can come from being present with your patient. And so anyway, I think time presence, listening even to the things that don't seem like they're going to be useful. And then of course, you can imagine for me, the other thing I would say is just thinking outside the box that I was told, we've run out of options. There is nothing more that we can do for you. And then I learned that there were 3000 other drugs for other diseases, and it turned out there was a drug for me. And so, you know, opening up our minds to the world we're in, which is the story is there are two drugs for this disease, which is probably right. But maybe one of the other 3000 drugs could actually also help this disease being open to it while also being evidence based. I think that's I think that's where we need to be.
Henry Bair: [00:59:56] Well, with that, we want to thank you again for so generously taking your time to share your story and the incredible insights you have learned along the way.
David Fajgenbaum: [01:00:06] Oh, well, thank you both so much for having me. And thank you so much for this podcast and what you all do, as you said, to provide this important resource and experience for young medical students and young professionals. So thank you.
Henry Bair: [01:00:18] Well, it's our honor and pleasure to be able to share stories of remarkable individuals like yourself.
Tyler Johnson: [01:00:25] I will say just sort of off the record. I mean, I your story leaves me speechless. I mean, we've talked to lots of people with really who have done amazing things and seen and experienced amazing things. But I your story pretty much is very close to leaving me speechless.
Henry Bair: [01:00:44] Oh, we're still recording, so that might end up on the record.
Tyler Johnson: [01:00:48] I mean, guess if, you know, if this goes on the record, so be it. But I just, I don't know, like in the same way that I have to imagine that you can't hear the stories of the people who come to you for help without this visceral sense of what it would be like to be in their shoes because you were in their shoes. I just on hearing your story, I can't help but think of medical students that I know and teach, Right? And and like, you know, one thing that is not as rare as I wish it were is the idea of someone very young getting very sick. Right. Like I have known multiple residents who have been diagnosed with cancer and I've even known house staff who have died. Even having said that, what is still exceptionally unusual about your case is both the fact that you kept getting so sick and then getting better and that there was really no explanation for either side of the coin, right? Either why you were getting really sick or why you were suddenly getting better. And I just I can't help but put myself in the shoes. Of one of the medical school faculty who knew you and then was taking care of you and trying to figure out what was going on. And I just I mean, the story is just almost too much. Like, I feel like on the one hand, of course, it's unimaginably inspiring, but on the other hand, I feel like just the prospect of that is going to be keeping me up at night.
David Fajgenbaum: [01:02:10] Well, and you know, you talk about the professor side of things. So two of my favorite med school professors, one of them was an is an is an ICU doctor, although he's retired. The other one is a GI surgeon. And I just saw the ICU doctor. He's as I mentioned, he's now retired. A few weeks ago I was with a friend and introduced him. I said, This is Dr.. I guess I can say Doctor Lincoln, you know, he took care of me in the ICU and and he told me, he said, I still think about that often. You know, that. And this was this was 13 years ago. And it was because, to your point, it was so painful for him to watch. And again, it's painful for us to see any patient suffer. But but I think, you know, I already had a relationship with him beforehand. And so typically, you don't have a relationship with your patient before you meet them. Right. But we already had a relationship and, you know, and then my other I said my other favorite doctor, you know, mentor was this GI surgeon. And he wanted to fix me so bad he was like, Let me get in there. I'm going to operate. I don't know what's in there. But like, I mean, he seriously he was like he was like, let me open things up because I had this horrible abdominal pain because of all the acids.
Tyler Johnson: [01:03:16] Okay, we're just going to, like, go in and do an il6 ectomy just, you know, surgery, take it out,
David Fajgenbaum: [01:03:21] Il6-Ectomy! And so, I mean, he was seriously he was like, he's like, let me just cut open your abdomen. Let's look in there. You know, I'm going to find something. I'm going to take it out. And and that's what my doctors wanted to do, right? That's because that's what you want to do, right?
Tyler Johnson: [01:03:34] Of course that's what you.
David Fajgenbaum: [01:03:35] Want to do. You just want to fix it. Everyone just wants to fix it. And. And no one could do it. No one. You know, it took 11 weeks until we finally did it.
Tyler Johnson: [01:03:43] I mean, you know, I'm sitting here joking about an il6 ectomy as if the idea of surgery is totally crazy. But let's really be honest. I mean, giving you cytoxan and adriamycin, which are like super powered chemotherapy drugs for a thing that they don't even know if it's cancer yet. I mean, that's basically the medical oncology version of doing a surgery when you have no idea what you're going to do a surgery about. I mean, that's just sort of the I mean, I that is a very big step to take when you don't even yet have a diagnosis. It's the kitchen sink.
David Fajgenbaum: [01:04:11] You're right. That's the oncology version of Open Up the Abdomen. Yes.
Henry Bair: [01:04:16] Yeah. It's incredible. And, you know, it really does bring me a lot of joy to know how well you've done since coming from that terrible place 13 years ago. And I have every reason to believe that this is going to inspire a lot of patients and clinicians alike.
Tyler Johnson: [01:04:35] All right. Well, thank you so much, David. You've been so generous with your time.
David Fajgenbaum: [01:04:39] This has been really fun. Thanks so much for having me on. And it really, really enjoyed it. You guys, you guys are awesome. And this was just it's just just a lot of fun.
Henry Bair: [01:04:49] Thank you for joining our conversation on this week's episode of The Doctor's Art. You can find program notes and transcripts of all episodes at www.thedoctorsart.com. If you enjoyed the episode, please subscribe rate and review our show available for free on Spotify, Apple Podcasts or wherever you get your podcasts.
Tyler Johnson: [01:05:07] We also encourage you to share the podcast with any friends or colleagues who you think might enjoy the program. And if you know of a doctor, patient or anyone working in health care who would love to explore meaning in medicine with us on the show, feel free to leave a suggestion in the comments.
Henry Bair: [01:05:21] I'm Henry Bair.
Tyler Johnson: [01:05:22] And I'm Tyler Johnson. We hope you can join us next time. Until then, be well.
