Shawn Ryan Show #240 - Dr. David Fajgenbaum

Can AI Find Cures to Rare Diseases Using Existing Medicine?
Release Date: September 29, 2025

Episode Overview

This rich and emotional episode of the Shawn Ryan Show features Dr. David Fajgenbaum, a physician-scientist whose relentless pursuit to cure his own rare and deadly disease led him to pioneer drug repurposing—finding life-saving treatments in already existing medicines. Dr. Fajgenbaum shares his traumatic yet inspiring personal journey through multiple brushes with death and explains how artificial intelligence (AI) is revolutionizing the hunt for hidden cures for rare and terminal diseases. The conversation covers the failures and challenges of the medical system, the bottleneck in drug discovery, pharmaceutical industry roadblocks, and the mission of his nonprofit, EveryCure. Throughout, Shawn Ryan and Dr. Fajgenbaum dig deep into the human drama and hope inherent in battling disease.

Key Topics & Discussion Points

1. Dr. Fajgenbaum's Personal Backstory

[09:31–25:44]

• Early Life & Inspiration: Grew up in Raleigh, NC; aspired to be a college quarterback; mother diagnosed with brain cancer while he was at Georgetown.
• Mother’s Illness & Legacy: Her battle with brain cancer—a mix of tragedy and humor (15:26)—shaped his worldview and career path. Before her death, he promised to dedicate his life to finding treatments for patients like her and to support grieving students.
  • Quote: “I promised her I would dedicate my life to trying to find treatments for patients like her. ... She had very limited speech towards the end... the two words she could still say were ‘unconditional love.’” (13:32)
• Medical School Struggles: While a med student at Penn, he fell critically ill with a then-unknown disease (Castleman’s), faced multiple near-death relapses, and experienced what it’s like to say goodbye to loved ones.

2. Surviving Terminal Illness: Mindset & Family

[21:23–27:47]

• Facing Death Repeatedly: Describes brutal hospitalizations, being read his last rites, and relying on his vision for the future and support from loved ones to survive.
  • Quote: “My sister Gina was holding my hand ... and she said, just breathe Dave, just breathe... If she hadn’t said that, I’m not here.” (25:36)
• Fight vs. Acceptance: Insightful discussion on the human ability to fight for survival and the critical importance of support during crisis.

3. The Path to Self-Cure

[33:25–39:40]

• After surviving on experimental drugs and multiple chemotherapies, Dr. Fajgenbaum realizes existing medications may already contain “hidden” cures for rare diseases like his.
  • Realization: “None of them were made for Castleman disease... what if there’s an eighth drug for lymphoma or a ninth drug for something else that could work for Castleman’s?” (36:54)
• Hands-on Research: Amassed and analyzed his own blood samples and data, ultimately discovering that the generic drug sirolimus/rapamycin, used in transplantation, could put his disease into long-term remission.
• More Than Survival: This “N-of-1” experiment ignites a mission to find similar hidden treatments for others.

4. Barriers in Healthcare & Drug Repurposing

[04:50–08:40; 56:36–61:35]

• Roadblocks: The main obstacle in drug repurposing is lack of financial incentive: 80% of existing drugs are generic, so no profit motivates research for new uses (04:50).
  • Quote: “It’s not profitable to find a new use for them. So someone's got to do it.” (04:50)
• Structural Issues: Insurance-based healthcare often incentivizes quick fixes, with little time or systemic support for deep diagnostics or off-label research.
• Pharma Realities: Pharmaceutical companies focus on profitable conditions while rare and generic drugs languish without sponsors.

5. The EveryCure Project & Role of AI

[52:09–77:32]

• Birth of EveryCure: A nonprofit co-founded by Dr. Fajgenbaum, leveraging AI to systematically analyze vast biomedical data and identify promising drug-disease matches across all 4,000 FDA-approved drugs and 18,000+ diseases.
  • Quote: “We joke that EveryCure is the biggest drug company of all time... but we’re also the smallest because we don’t own any drugs.” (61:41)
• Technical Approach: Uses a “biomedical knowledge graph” to map out connections between drugs, genes, proteins, and diseases. Machine learning algorithms score 75 million possible drug-disease matches, highlighting those with the highest potential.
  • Breakthroughs: Accelerated review—algorithmic time dropped from 100 days to 17 hours (75:36).
  • Careful Validation: Emphasizes that AI provides a prioritization, but human clinical and lab research must validate the match before recommending treatments.
• Scaling Up: Currently 50 team members; goal is to expand efforts akin to big pharmaceutical companies, but focusing exclusively on non-profitable matches.

6. Stories of Drug Repurposing Success

[45:48–67:41]

• Castleman’s Disease: Sirolimus helped Dr. Fajgenbaum into remission and is now effective for 25% of Castleman’s cases globally.
  • **“The first patient ... was this young boy named Joey...Critically ill—within days, things started getting better. ... He’s now a sophomore in college.” (45:48–47:06)
• Cancer (Angiosarcoma): Used immunotherapy (pembrolizumab) initially indicated for melanoma/lung cancer to treat an otherwise terminal cancer patient, leading to unprecedented survival milestones.
  • Quote: “He walked his son down the aisle a year ago. ... Last weekend he walked his daughter down the aisle.” (65:22)
• Ultra-Rare Disease (Bachmann Bupp syndrome): Repurposed DFMO, enabling children who were previously bed-bound to stand, walk, and live fuller lives.

7. Communication & Dissemination of Repurposing Discoveries

[68:21–73:28]

• Lack of Centralized Database: Information on repurposed uses is scattered; often moves through conferences, journals, or the efforts of committed patient advocates.
  • Quote: “Honestly, right now, it happens very randomly and sporadically. ... It’s not a doctor’s job to be PR for how to treat patients.” (68:53)
• Role of Media & Collaboration: Podcasts, social media, and disease foundations are pivotal for spreading awareness.
• Hope for Open Access: Aspires to create/expand accessible databases so the world’s clinicians and patients can benefit systematically.

8. Broader Healthcare and Societal Questions

[82:01–99:38]

• Cancer Prevention: Discusses a trial showing lidocaine injected near breast tumors reducing recurrence—an example of a simple old drug with new preventive purpose.
• Inflammation, Sugar, and the Environment: Agrees that environmental factors raise cancer/disease risk, but emphasizes the complexity and multifactorial origins.
• Holistic vs. Pharma: Dr. Fajgenbaum calls for nuance and data-driven choices, warning against wholesale rejection or acceptance of either natural or pharmaceutical remedies.
• Stem Cell Treatments Abroad: Comments on why innovative treatments (e.g., stem cells in Argentina) are sometimes unavailable or slower to approve in the US—often due to risk-benefit calculations by regulatory agencies.

Notable Quotes & Memorable Moments

• On Purpose: “There was just something that clicked in me and just snapped, which was like, I’m going to dedicate my life to getting revenge against these things...” – Dr. Fajgenbaum (16:11)
• On Patient Survival: “If the 10 people that got the drug all do better and survive ... That’s sort of night and day.” (Dr. Fajgenbaum, 67:47)
• On Impact: “What I found is the most incredible part is when I get to hear about what these people are doing basically in this overtime that they’ve got.” (Dr. Fajgenbaum, 47:23)
• On Communication: “A tweet, social media post can be the difference between life and death for someone, man.” (Dr. Fajgenbaum, 71:02)
• Message from His Mother: “Bold in the truth, courageous in freedom, constant in responsibility, generous in love, invincible in hope.” (Quote from Pope John Paul II, found in her purse, 102:33)

Timestamps: Important Segments

• Personal Story, Family, and Promise: 09:31–18:13
• Critical Illness and Near Death Experiences: 19:11–27:47
• Discovering Repurposed Cure (Sirolimus): 33:25–41:46
• Barriers in Healthcare & Pharma: 04:50–08:40, 56:36–61:35
• EveryCure, AI, and Drug-Disease Matching: 52:09–77:32
• Patient Impact Stories: 45:48–65:51
• Dissemination & Awareness Issues: 68:21–73:28
• Broader Healthcare Questions (Prevention, Environment, Holistic Medicine, Stem Cells): 82:01–101:13
• Mother’s Final Message: 101:17–103:00

Summary Table: EveryCure at a Glance

| Aspect | Details | |-----------------------------------|--------------------------------------------------------------------------| | Mission | Systematically identify and validate hidden uses for existing medicines | | Method | Biomedical knowledge graph + AI to generate drug-disease match scores | | Scope | 4,000 approved drugs × 18,000 diseases (75 million possible matches) | | Successes | 14 drugs advanced for new diseases to date; 9 active programs | | Funding | U.S. Government (ARPA-H), philanthropy, public donations | | Impact So Far | Examples: Castleman’s remission, rare pediatric treatments, cancer cases | | Communication Strategies | Peer-reviewed papers, patient advocacy, mainstream and alternative media |

Call to Action

• To Support: Donate at EveryCure.org/donate
• To Spread Awareness: Share stories, leverage podcasts and social media, encourage database/database improvements
• For Patients & Families: Understand that persistence, networking with rare disease groups, and asking about off-label and repurposed drug options can save lives.

Final Thoughts

The episode highlights the overlooked power of existing medicines when equipped with new data, relentless hope, and the right mindset. Dr. Fajgenbaum’s life—and those he's helped save—stands as testament to science’s capacity to innovate, adapt, and triumph when fueled by empathy, intelligence, and urgency.

End of Summary