Freakonomics Radio Episode 664

Are Thousands of Medical Cures Hiding in Plain Sight?

Date: February 20, 2026
Host: Steve Levitt (Guest Host), with Stephen Dubner, Freakonomics Radio Team
Guests: David Fajgenbaum (EveryCure, University of Pennsylvania), Heather Stone (FDA), Chris Snyder (Dartmouth), Saran Chathek (Duke/Market Shaping Accelerator)
Summary by: Your Podcast Summarizer

Episode Overview

This episode explores the vast, overlooked world of "drug repurposing"—finding new, life-saving uses for existing medicines. Guest host Steve Levitt interviews researchers, economists, and policymakers to uncover why medical cures may be going ignored due to broken incentives, slow adoption, and insufficient data-sharing—even though the drugs are already available and affordable. The central question: Can we uncover hidden cures and bring them to patients faster?

Major Discussion Points & Insights

1. Hidden Cures and Unexplored Treatments

• Rare diseases like Balamuthia (00:01–03:21) have no FDA-approved treatments, yet off-label drugs (like Nitroxyline for a brain-eating amoeba) can occasionally save lives.
  • Quote: "For a disease that had a 90% fatality rate, to have two patients survive like that was pretty remarkable." – Heather Stone (02:45)
• Most human diseases (about 75%) lack any FDA-approved treatment. Many drug alternatives may be hiding in plain sight.

2. David Fajgenbaum’s Personal Story & Inspiration

• Fajgenbaum’s journey: star quarterback whose life changed after his mother's brain cancer diagnosis led him to medicine (04:13–06:40).
• While in med school, he was struck by Castleman Disease, a deadly rare disorder with no known cure.
  • Quote: "My doctors explained to me that we were out of options...I realized that if I wanted any chance to survive, I would have to really turn my hope into action and start trying to find a drug that could save me." (09:26)
• He coordinated international research, stockpiled his own blood samples ("blood in the freezer"), and ultimately identified the MTOR pathway as a key disease driver (12:52–14:20).

3. Discovery and Repurposing: Sirolimus/Rapamycin

• Fajgenbaum linked Castleman disease’s biology to the drug Sirolimus (rapamycin), an immunosuppressant discovered on Easter Island.
  • Quote: "MTOR actually stands for mammalian target of rapamycin. Like, this thing in our body is inhibited so well by this drug rapamycin, that we named the thing after the drug." (15:12)
• Sirolimus saved his life and several other patients (though not all).
  • "We’re four for four, basically...I thought to myself, we did it. We took down Castleman’s... Unfortunately, the fifth patient we tried it on, it didn’t work in." (16:53, 17:25)

4. Scaling Repurposing Efforts: EveryCure and AI

• Fajgenbaum co-founded EveryCure, scaling his approach with AI to match thousands of drugs to diseases (18,000 diseases x 4,000 drugs).
• Uses "biomedical knowledge graphs" and prioritizes high-probability matches for human expert review.
• Example: Lidocaine, a common anesthetic, drastically reduced mortality in breast cancer surgery (by 29%) when injected around tumors—yet is ignored due to lack of financial incentives (21:00–23:04).
  • Quote: "There is no entity that's financially incentivized to do more studies with lidocaine or to make sure that every patient who has breast cancer asks their doctor to have lidocaine injected..." (22:37)

5. The Incentive Problem

• Drug repurposing costs about 1% of developing a new drug, but offers “zero financial upside” due to patent and regulatory structures (23:21–24:48).
• Quote: "It's much, much, much less expensive to do it, there is zero financial upside. Even though it's going to help a lot of patients, no one's going to make any money off of it." – David Fajgenbaum (24:21)
• Levitt highlights the economic misalignment: "What's so frustrating...the science is so much easier, but the economic incentives are almost totally absent." (23:04)
• Key Question: How can society realign incentives so repurposing research actually happens?

6. Market-Based Solutions: Advanced Market Commitments

• Levitt interviews Dartmouth economist Chris Snyder about market-shaping mechanisms like Advanced Market Commitments (AMCs) (26:46–34:08).
  • Explains AMC's huge success incentivizing new vaccines (e.g., pneumococcal, COVID-19), showing how pull funding (paying for results) can unlock innovation.
  • Quote: "You dangle market incentives...pull funding is, in a sense, payment for success." – Snyder (29:19)
• Discusses why such approaches haven’t been more widely applied to drug repurposing.

7. A New Proposal: Pull Funding for Repurposed Generics

• Market Shaping Accelerator and Duke Margolis Center propose a federal program that would pay out based on health impact if a new use for a generic succeeds (37:53–40:29).
  • Quote: "We think this would cost roughly $1 billion per successful opportunity..." – Saran Chathek (38:08)

Notable Quotes & Memorable Moments

• “I sure as hell better spend the rest of my life looking for more of these things for more people.”
  – David Fajgenbaum, reflecting on his motivation (53:13)
• “On average, it takes 17 years for a new medical advancement to be adopted.”
  – Heather Stone (42:56)
• "Generally, the phrase that's thrown around is: it's not considered sexy enough. Right. And so I think that's a fundamental problem."
  – Heather Stone, on why repurposing research is ignored (50:19)

Key Segments & Timestamps

| Timestamp | Segment | Key Topics & Highlights | |-----------|--------------------------------------------|-------------------------------------------------------------| | 00:01 | Opening Story: Balamuthia | Untreatable diseases, off-label drug saves lives | | 04:13 | Fajgenbaum’s Background | Personal journey, family, pivot to medicine | | 06:40 | Castleman Disease Diagnosis | Rare, deadly, no known cure | | 10:18 | Self-Driven Medical Research | Building networks, collecting data, blood in freezer | | 12:52 | Discovery: MTOR Pathway | Linking pathway to sirolimus/rapamycin, personal recovery | | 18:13 | Launching EveryCure | Drug repurposing at scale, AI applications | | 21:00 | The Lidocaine Example | 29% mortality reduction, no incentive for adoption | | 23:21 | Economics of Drug Repurposing | Cost vs. incentive, system failures | | 26:46 | Market Shaping Accelerator & AMCs | Economic theory, successful vaccine incentives | | 34:27 | Pull Funding for Generic Repurposing | Policy proposal, cost-saving, practical hurdles | | 42:56 | FDA’s Heather Stone: Adoption Barriers | Slow uptake, Cure ID, data registry for off-label use | | 44:03 | Personal Experience with Repurposed Drug | Stone’s fibromyalgia, Lyrica success story | | 44:57 | Cure ID Platform | Data sharing, pragmatic adoption hurdles | | 49:00 | Pull Funding - Radical New Model | Medicare/Medicaid link, near- and long-term feasibility | | 50:19 | Repurposing: Not Sexy Enough | Funding gaps, priorities in medical research | | 51:47 | EveryCure’s Funding and Ambition | $100M raised, target to help 15-25 conditions in 5 years | | 53:13 | Fajgenbaum’s Drive: Patient Impact | Central mission: save more lives, sense of urgent purpose |

In the Words of the Speakers

• David Fajgenbaum (18:13):
  "From the moment that that drug, Sirolimus, started saving my life, I just haven't been able to stop thinking about how many more drugs are out there that could treat more patients in need... So the question became, well, how many more things are there out there that we could potentially uncover to save lives today? Because these drugs are already at the pharmacy."

• Chris Snyder, on market incentives (29:19):
  "You dangle market incentives and the right parties who are going to actually have the best ideas will, in a sense, self organize just as markets often do, and bring themselves through the pipeline to try to get that reward at the end...pull funding is, in a sense, payment for success."

• Heather Stone (44:03):
  "I have benefited enormously from repurposed drugs with my own health issues...Eventually, a drug called Lyrica, which had been approved for diabetic neuropathy, started reporting...they noticed large improvements in their fibromyalgia symptoms...That has been a treatment...for almost two decades and is really the reason that I'm able to do the job that I do today."

Conclusion: Hidden Cures, Human Stories, Economic Puzzles

This episode paints a powerful, multidimensional picture:

• The science of repurposing is surmountable, but incentives, funding, regulation, and data-sharing all conspire to keep cures hidden.
• Personal stories (Fajgenbaum, Stone) illuminate impact and urgency.
• Innovative economic mechanisms—like pull funding—show a path forward, but translating them to policy remains an open challenge.
• Ultimately, thousands of lives could be transformed if even a fraction of existing drugs were systematically tested and adopted for new uses.

“There’s a drug that could help them, and there’s someone suffering right now and we haven’t found it yet... I sure as hell better spend the rest of my life looking for more of these things for more people.”
– David Fajgenbaum (53:13)

For more: Explore Cure ID, EveryCure, and the Market Shaping Accelerator.

This summary skips all ad breaks, show credits, and focuses solely on the episode’s core narrative, discussion, and actionable insights.