The guest
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).
What this episode covers
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.
Recommended on this episode
BookRecommendedISBN verified
The Comfort Crisis
Michael Easter
“an incredible book, really... an important book”
“We had a guest on this podcast, Michael Easter. He wrote the book "The Comfort Crisis." It was an incredible book... an important book”— Andrew Huberman
Also referenced (named, not recommended)
BookReferencedISBN verified
Protocols: An Operating Manual for the Human Body
Andrew Huberman
“It's entitled "Protocols: An Operating Manual for the Human Body." This is a book that I've been working on for more than five years”— Andrew Huberman
ProductReferenced
Sirolimus (Rapamycin)
Wyeth Pharmaceuticals
“Sirolimus had never been used before. Rapamycin's the other name for this drug... it's approved for organ transplant rejection”— David Fajgenbaum
ProductReferenced
Tocilizumab
Kazu Yoshizaki
“It's called tocilizumab, and it was made by a doctor named Kazu Yoshizaki... it was made for Castleman's in Japan”— David Fajgenbaum
ProductReferenced
Lidocaine
generic
“women who had localized breast cancer, if they had lidocaine injected around the tumor before surgery... there was a 29% reduction in mortality”— David Fajgenbaum
ProductReferenced
Thalidomide
generic
“the first one's thalidomide. You probably have heard about the horrible birth defects that thalidomide caused... it's FDA-approved for leprosy”— David Fajgenbaum
ProductReferenced
Pembrolizumab
generic
“one of my favorite examples is a drug called pembrolizumab, that is now used for dozens of cancers, but initially it was first developed for melanoma”— David Fajgenbaum
ProductReferenced
Colchicine
generic
“colchicine is typically utilized for gout... it has a very substantial reduction in heart disease risk if you had a prior heart attack”— David Fajgenbaum
ProductReferenced
DFMO (eflornithine)
generic
“no one should suffer from Bachmann-Bupp without being on DFMO... a drug that was made for African sleeping sickness”— David Fajgenbaum
ProductReferenced
Ruxolitinib
generic
“we recommended her doctor try ruxolitinib, first time ever for Castleman disease, and she responded incredibly well”— David Fajgenbaum
ProductReferenced
Adalimumab (TNF inhibitor)
generic
“we gave him adalimumab, and he responded incredibly well. He's been doing great now for two years. Published in "The New England Journal of Medicine"”— David Fajgenbaum
ProductReferenced
Viagra (sildenafil)
Pfizer
“Many folks have probably heard about how Viagra was repurposed from heart disease to its well-known use... also been repurposed for a rare pediatric lung disease.”— David Fajgenbaum
ProductReferenced
Cialis (tadalafil)
Eli Lilly
“isn't it that the cousin of Viagra, Cialis, was initially tadalafil, used to encourage prostate health, circulation to the prostate”— Andrew Huberman
ProductReferenced
Aspirin
generic
“aspirin also has been shown to reduce risk of recurrence of colon cancer. Particularly, individuals with colon cancer who have a mutation”— David Fajgenbaum
ProductReferenced
Nicorette (nicotine gum)
Nicorette
“I noticed he chewed six pieces of Nicorette inside of the 45 minutes we met... "Nicotine is protective against Alzheimer's and Parkinson's."”— Andrew Huberman
ProductReferenced
Creatine
generic
“I've been taking creatine since my teens because I heard back then that it would help make me stronger and it'll make you stronger.”— Andrew Huberman
ProductReferenced
Mucuna pruriens
generic
“Mucuna pruriens is this velvety bean that is 99% L-DOPA... You can buy this over the counter.”— Andrew Huberman
Big reveals from this episode
- 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.
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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