Armchair Expert with Dax Shepard

Guest: Dr. David Fajgenbaum
Episode: On Repurposing Medicine
Date: November 26, 2025

Episode Overview

This episode features physician, scientist, and bestselling author Dr. David Fajgenbaum, whose remarkable journey includes surviving his own rare disease (idiopathic multicentric Castleman disease) by discovering and repurposing an existing FDA-approved drug. Dr. Fajgenbaum shares his moving personal story, discusses the wide-reaching potential of drug repurposing for rare and common diseases, and introduces Every Cure, a nonprofit using AI to unlock treatments hiding in plain sight. The conversation is peppered with humor, honesty, reflections on grief, and moments of awe at scientific possibilities.

Key Discussion Points

1. Early Life & Football at Georgetown (02:22–08:32)

• Background: Born in Raleigh, his father was an orthopedic surgeon for North Carolina State’s football team, fostering David’s love for football.
• College Experience: Played tight end at Georgetown, where he was a driven student-athlete with intense work ethic (“I was totally, totally obsessed and just worked like crazy.” – Fajgenbaum, 07:10).
• Shift in Motivation: His mother’s diagnosis with glioblastoma during his freshman year redirected his focus from sports medicine to seeking cures for deadly diseases.

"The moment my mom got sick with brain cancer, all those posters I had about football and all the thoughts… they were out of my mind.” (Fajgenbaum, 11:31)

2. Grief and Creating AMF for Bereaved Students (08:32–14:46)

• Processing Loss: Struggled with grief after his mother’s passing, channeling emotion into action by creating AMF, a support group for grieving college students.
• Instrumental Grieving: Recognized, with Dax’s help, that he initially coped by “doing” (founding nonprofits, focusing on studies) instead of sitting with discomfort.

“I think that the way that I decided to start dealing with my grief was...you create something and you pour it into that thing. And this is actually something that a lot of men do when they deal with grief.” (Fajgenbaum, 14:53)

3. Medical Training & The Onset of Castleman Disease (16:27–20:53)

• Oxford & Penn: Studied medicine and public health, returning to the US for medical school at Penn.
• Symptoms & Hospitalization: Suddenly developed severe fatigue, swollen lymph nodes, and organ dysfunction during his third year. Went from bench-pressing 325 lbs to being critically ill.

“I started feeling more tired than I ever felt before...Noticing lumps and bumps in my neck, which turned out to be enlarged lymph nodes.” (Fajgenbaum, 17:41)

4. Life-threatening Illness and Near Death (20:53–28:17)

• Critical Condition: Organs failed; gained 100 pounds of fluid; received last rites; spent seven weeks in the ICU. Initial high-dose steroids and chemotherapy provided only temporary relief.
• Castleman Diagnosis: Eventually diagnosed with a rare, deadly immune disorder, idiopathic multicentric Castleman disease—no known cure and an uncertain prognosis.

5. Scientific Investigation & Self-Experimentation (34:07–43:16)

• Relapses & Desperation: Multiple relapses; outlived all standard therapies. Noted that all chemotherapies used were for other diseases, sparking the idea to search for more existing drugs.
• Taking Charge: Read thousands of scientific papers, built an international collaborative network, and began experimenting on his own blood.
• Breakthrough: Discovered overactivity in a pathway called mTOR. Convinced doctors to try sirolimus (an mTOR inhibitor made for organ transplant rejection), which led to full remission.

“My idea was that if I could figure out what was wrong, I could then see, is there a drug that can reverse the thing that's wrong?” (Fajgenbaum, 38:06)

• Notable Quote:

"It's been over 11 and a half years that I've been doing great on this medicine. No relapses, full health." (Fajgenbaum, 43:18)

6. Broadening the Mission: Drug Repurposing for All (44:20–54:44)

• Lab at Penn & Every Cure Nonprofit: Dedicated career to finding new uses for existing drugs, especially for rare diseases.
• Barriers: Found that administrative and organizational challenges (not science alone) were the biggest obstacles—limited profit incentive for pharma to pursue generics for rare/other indications.
• Unsexy vs. Life-Saving: Drug repurposing is "recycling old drugs" (51:04), not seen as innovative, but can produce real breakthroughs.
• AI as a Force Multiplier: With thousands of drugs and diseases, artificial intelligence is critical for uncovering possible matches at scale.

“AI actually would allow us to say…we can look at all 4,000 drugs and all 18,000 diseases and let AI actually give us a score...something one lab never could, one person never could.” (Fajgenbaum, 54:13)

7. Every Cure’s AI Knowledge Graph & Success Stories (54:44–69:21)

• How the AI Works: Constructs a “knowledge graph” linking drugs, diseases, genes, and clinical data; learns patterns from documented treatments and scientific literature, then predicts new matches.

• Successes:

  • Angiosarcoma: A fatal cancer—AI found a drug that now gives 18% of patients years instead of weeks to live; saved Fajgenbaum’s uncle.
  • Nonverbal Autism: Folinic acid (a derivative of folate) helped some nonverbal autistic kids gain speech (“Within two weeks, [Ryan] told his dad for the first time ever...‘Daddy, I love you.’” – Fajgenbaum, 57:45).
  • Breast Cancer: Lidocaine injections around tumors prior to surgery show 29% mortality reduction in a large Indian clinical trial—yet almost no one uses it.
  • Botox for Depression: Fascinating studies showing mood improvements after forehead injections.
  • Bachmann Bup: DFMO repurposed to reverse deadly genetic disease in children.

• Notable Quote:

"Every one of these is why we started Every Cure. This is it, right? It's like this super rare disease, this super cheap drug that's been around for decades—no one's going to do the work to get it to every patient possible. But we can." (Fajgenbaum, 69:21)

8. Health Care Incentives & Systemic Obstacles (61:36–62:28)

• Profit Problem: 80% of existing drugs are generic; pharmaceutical companies lack profit incentive to fund trials or promote new uses.
• Nonprofit Solution: Every Cure operates as a nonprofit, aiming to address what for-profit entities cannot.

9. Call to Action: Awareness and Support (69:21–70:48)

• Ways to Help: Donate to www.everycure.org, spread awareness, and watch/share Fajgenbaum’s TED talk.
• Books: Read “Chasing My Cure” for deeper insight into Dr. Fajgenbaum’s journey.

Memorable Moments & Notable Quotes

• On Hope and Closure:
  “As someone who loves someone going through that stuff, you're always really having a hard time debating whether or not you're going to snuff out their hope or help them get to the part where we have closure.”
  — Dax Shepard (34:58)

• On Medical Incentives:
  “The people who are doing the work are not incentivized as the patients… but the people actually doing the work are not going to benefit from it the same way that they would a new drug.”
  — Fajgenbaum (51:16)

• On AI’s Potential:
  “You can gather information all you want, but to actually find patterns within information is so time consuming and nearly impossible for a human to do.”
  — Dax Shepard (50:15)

Essential Timeline & Timestamps

• [03:00] Georgetown football and pre-med ambitions.
• [08:32] Mother’s brain tumor diagnosis, forging a new sense of vocation.
• [11:16] Loss and grief—promises to mother become life’s mission.
• [16:27] AMF nonprofit founded for grieving students.
• [17:41] First symptoms of Castleman disease; denial and quick decline.
• [20:22] Hospital crisis; diagnosis and last rites.
• [32:13] Multiple relapses, desperate search for off-label treatments.
• [36:23] Founds Castleman Disease Collaborative Network.
• [38:06] Self-experimentation discovers mTOR abnormality.
• [43:18] Sirolimus leads to long-term remission; Fajgenbaum’s breakthrough.
• [44:40] Lab at Penn and launching Every Cure.
• [54:44] The critical role of AI.
• [57:45] Folinic acid and autistic children's speech gains.
• [69:21] Every Cure’s mission, impact, and ways to help.

Further Resources

• Every Cure: everycure.org – Donate, learn, share.
• Book: "Chasing My Cure" by Dr. David Fajgenbaum.
• TED Talk: Search “David Fajgenbaum TED Talk” or check Every Cure’s site.
• Contact: For direct stories or requests, reach Every Cure via their website.

Tone & Final Thoughts

In classic Armchair Expert fashion, the conversation is candid, funny, empathetic, and intellectually curious. Dax, Monica, and David openly discuss the emotional weight of illness, the frustration of medical bureaucracy, and the real hope represented by AI and drug repurposing. Fajgenbaum’s energy, optimism, and relentless invention—fueled by personal survival—make for one of the show's most inspiring medical stories.

“It's rare that I can say this to somebody, but I'm so happy you didn't make it in the NFL.” (Dax, 70:14)

If you’re curious about how thousands of lives could be saved by using the medicines already on our shelves, or want to contribute to the solution, this episode is essential listening.

Highlighted Quote Board

• “If you open up the book real quick. I showed Monica a picture. Open it up and go to this middle picture.” – Fajgenbaum [04:30]
• “My thing that I was channeling my time into was... schoolwork and this grief support group.” – Fajgenbaum [16:07]
• “You would think you'd be inoculated from this because you know about it. You're not.” – Dax [18:08]
• “There’s 4,000 drugs… How can you tell me we’ve tried everything?” – Fajgenbaum [34:43]

Take Action

• To support more life-saving breakthroughs, visit Every Cure
• Spread awareness about drug repurposing and the power of AI in medicine
• Read “Chasing My Cure” for more on Dr. Fajgenbaum’s journey

Episode draws to a close on a tone of gratitude, wisdom, and encouragement to look beyond traditional medical silos—a message as relevant for patients as it is for those in health care.