Dr. David Fajgenbaum — Professor of translational medicine and human genetics at the University of Pennsylvania and founder of the nonprofit Every Cure. A former Georgetown quarterback and MD who nearly died five times from Castleman disease before curing himself with the repurposed drug sirolimus (rapamycin).
The gist
Andrew Huberman talks with physician-scientist Dr. David Fajgenbaum about drug repurposing: the idea that many existing FDA-approved drugs could treat diseases other than the ones they're marketed for, but the system isn't built to find those uses, especially once drugs go generic. Fajgenbaum recounts his own near-death battle with Castleman disease, how he discovered sirolimus saved his life, and how his nonprofit Every Cure now uses AI and biomedical knowledge graphs to match all 4,000 approved drugs against all 18,000 human diseases. They discuss real cases (lidocaine for breast cancer, thalidomide for myeloma, pembrolizumab for angiosarcoma, colchicine for heart attack, DFMO for Bachmann-Bupp), the blurry line between supplements and pharmaceuticals, and the neuroscience of resilience via the anterior mid-cingulate cortex.
Big reveals
- Fajgenbaum's doctor told him there was nothing left to try; he refused, reasoning they hadn't tested all 4,000 approved drugs.
- An Indian trial of 1,600 women found lidocaine injected around a breast tumor before surgery cut 5-year mortality by 29%, yet uptake is near zero.
- At 25, a priest read Fajgenbaum his last rites; the Castleman diagnosis arrived only days before he would have died.
- On his fifth near-death relapse he wrote his will on a sheet of printer paper, then woke up two days later after high-dose Etoposide.
- Lab work on his own blood revealed mTOR overdrive; he prescribed himself sirolimus, never before used for Castleman's, and has now been in remission 11+ years.
- Discussion of GLP-1 drugs showing emerging benefits for Parkinson's symptoms, reduced Alzheimer's risk, and breast cancer.
- Huberman explains the anterior mid-cingulate cortex as the brain's seat of tenacity and 'will to live,' larger in super-agers.
Things worth remembering
- The average small-molecule drug binds 20 to 30 different proteins in the body, so a drug 'does' far more than its one approved use.
- There are 4,000 FDA-approved drugs for ~4,000 diseases, but 14,000+ diseases have no treatment, and 80% of approved drugs are already generic.
- Thalidomide, infamous for birth defects, is FDA-approved for leprosy and multiple myeloma due to its anti-angiogenic effect.
- Pembrolizumab put angiosarcoma patient Michael into a 9-year remission; he walked his daughter down the aisle nine years after being told he was out of options.
- Colchicine, used for gout for ~3,000 years, substantially reduces heart-attack risk in prior-heart-attack and diabetic patients once the dose was tweaked.
- A study in 'Cell' found multi-day sleep-deprived mice were killed by a cytokine storm (including IL-6), not by lack of sleep directly.
- Rapamycin (sirolimus) is a naturally occurring compound discovered in soil from Rapa Nui (Easter Island) by a Wyeth researcher.
- Mucuna pruriens, a velvety bean sold over the counter, is roughly 99% L-DOPA.
- Fajgenbaum's lab has now found 14 drugs that work for diseases they weren't intended for.
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