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The Blurry Line Between Supplements and Prescription Drugs: The Mucuna Pruriens Example
Andrew Huberman discusses Mucuna Pruriens, a natural source of L-dopa, available over-the-counter, highlighting the often-blurred distinction between supplements and prescription drugs and the critical issue of unregulated over-the-counter products.
Every Cure's Non-Profit Model: Government and Public Funding for Drug Repurposing
Dr. David Fajgenbaum details Every Cure's unique funding structure, with half coming from the US government (ARPAH) and the other half from individual donors, underscoring their commitment as a non-profit to repurpose existing drugs without financial gain.
Colchicine: A 3000-Year-Old Remedy for Gout
Dr. Fajgenbaum shares the fascinating ancient history of colchicine, a drug used for gout for millennia, tracing its origins back to wealthy Egyptians who discovered its benefits for alcohol-induced gout 3000 years ago.
Every Cure's Rigorous Approach to Safe Drug Repurposing
Dr. David Fajgenbaum explains Every Cure's strategy for mitigating risks in drug repurposing, emphasizing avoiding speculation, conducting rigorous lab and clinical studies, and empowering physicians and patients through education for shared decision-making.
The Rise of Health Self-Advocacy: Why You Can't Be a Passive Patient Anymore
Andrew Huberman and Dr. Fajgenbaum discuss the growing importance of self-advocacy in health, especially since 2020. They emphasize that individuals are critical elements in their own health journeys and should not be passive participants, highlighting common misperceptions about existing treatments and the need for greater personal agency.
The Hidden Powers of Drugs: Why One Drug Does Many Things
Dr. Fajgenbaum explains that the average small molecule drug binds to 20-30 different proteins in the body, meaning it's doing 'a lot of other things' beyond its primary intended use. This fundamental pharmacological principle highlights why many beneficial drug repurposing opportunities are missed, as these 'other roles' often fall through the cracks if not explored early in a drug's development.
Every Cure: AI-Powered Search for New Uses for Old Medicines
Dr. Fajgenbaum introduces his nonprofit, Every Cure, which addresses the lack of an integrated medical database. He explains how they utilize biomedical knowledge graphs, AI, and machine learning models to systematically quantify the likelihood of every drug treating every disease, with nine active programs aimed at translating promising matches into patient treatments.
The Urgent Need for AI-Driven Healthcare Databases
Andrew Huberman discusses the potential of AI to revolutionize healthcare by analyzing PubMed data to provide actionable medical advice and identify the best treatment groups for specific diseases, highlighting the current lack of organized, accessible information.
Open Evidence: A GPT for Healthcare & Validating Drug Connections
Dr. Fajgenbaum discusses the concept of a centralized healthcare database, mentioning a company called Open Evidence attempting to create a GPT for healthcare. He explains his own work focuses on validating drug connections in the lab and clinical trials to ensure effective treatments are easily discoverable.
How to Join the Every Cure Mission: Support Drug Repurposing
Dr. David Fajgenbaum outlines various ways individuals can get involved with Every Cure, from sharing personal drug experiences and signing up as experts to raising awareness on social media and donating to support their non-profit work in drug repurposing.
The Deadly Link Between Sleep Deprivation and Cytokine Storms
Dr. Fajgenbaum discusses a study where multi-day sleep-deprived mice died from a cytokine storm, highlighting that sleep deprivation can disrupt immune balance, leading to excessive cytokine production and death. This research suggests a direct link between lack of sleep and severe immune system overactivation, relevant to conditions like Castleman's disease.
The Correlation Between Hard-Driving Lifestyles and Autoimmune Diseases
Andrew Huberman and Dr. Fajgenbaum discuss the anecdotal observation that highly ambitious, hard-driving individuals often face severe health issues like cancers and autoimmune diseases. They explore the connection between chronic stress, lack of sleep, and immune system dysregulation, noting strong data linking stress to autoimmune disease flares, while questioning if it's a causative factor.
The Flaws in Biomedical Research: From Santa Claus to Independent Investigators
Dr. Fajgenbaum introduces his 'Santa Claus theory' of civilization, an idealistic view of collaborative medical research that he later realized was far from the truth. Andrew Huberman expands on this, criticizing the 'independent investigator model' and advocating for a shift towards collaborative research focused on solving diseases, rather than individual recognition.
The 'Lone Wolf' Approach to Repurposing All FDA-Approved Drugs for All Diseases
Dr. Fajgenbaum describes his unique and systematic approach to drug repurposing, where he is actively trying to match all 4,000 FDA-approved drugs with all 18,000 human diseases. He explains that he is likely the 'lone wolf' in this comprehensive, 'all versus all' strategy, highlighting the current scientific incentives that often prioritize discovering new drugs over finding new uses for existing ones.
From Personal Cure to Every Cure: How AI is Revolutionizing Drug Repurposing
Dr. Fajgenbaum recounts the evolution of his work, from discovering Sirolimus for his own Castleman's disease to treating other patients, and then finding additional repurposed drugs for different conditions. This success culminated in the realization that a systematic approach was needed. He explains how his organization, Every Cure, now utilizes artificial intelligence to scan all 4,000 FDA-approved drugs against all 18,000 human diseases to find new treatment opportunities at scale, moving beyond 'Hail Mary' approaches to proactively match drugs to diseases.
AI-Powered Discovery: TNF Inhibitor Saves Castleman's Patient
Dr. Fajgenbaum shares a recent success story from Every Cure: a patient named Al with a deadly subtype of Castleman's disease who wasn't responding to any treatments. Their machine learning algorithm identified a TNF inhibitor (adalimumab) as the number one ranked drug for Castleman's. When administered, the patient responded incredibly well, highlighting the power of AI in discovering unexpected and life-saving repurposed drug applications, with the results even published in the New England Journal of Medicine.
The Dangers of Novel Drug Applications: Lessons from Gene Therapy and Supplements
Andrew Huberman discusses the inherent risks and public fear associated with using existing drugs in novel ways, citing historical examples like the gene therapy death and the contaminated tryptophan incident that set back entire fields due to a single adverse event.
AI's Role in Connecting Biomedical Knowledge for Drug Discovery
Dr. David Fajgenbaum explains that AI's most powerful application in drug discovery isn't simulation, but rather finding novel connections between existing, disparate pieces of biomedical research to uncover new therapeutic uses.
The Heartbreaking Randomness of Healthcare Outcomes
Dr. Fajgenbaum laments the inherent randomness within the healthcare and biomedical research system, illustrating how access to a specific drug can be a matter of luck, leading to vastly different life outcomes for patients.
Why We Talk About Creatine More Than Aspirin's Cancer Benefits
Andrew Huberman points out the disparity in public discourse, where supplements like creatine receive extensive attention for mild cognitive benefits, while established drugs like aspirin, with significant potential for colon cancer and heart attack prevention, are less discussed due to fear of self-medication.
The Medical System's 'Giant Blind Spot': Uncovering Cures in Existing Drugs
Andrew Huberman introduces Dr. David Fajgenbaum and his groundbreaking work. He explains that the medical profession often overlooks existing treatments for diseases deemed incurable, not due to malice, but because of systemic issues in how drugs are studied, patented, and categorized. This moment highlights the vast untapped potential of approved drugs and the need for greater awareness and a different approach.
Andrew Huberman's Vision for a Personalized Health Database
Andrew Huberman expresses his desire for a comprehensive, personalized database that would inform individuals, like a 50-year-old male, about all available over-the-counter or prescription drugs and molecules that could potentially extend life and reduce specific health risks, beyond common discussions around supplements.
African Sleeping Sickness Drug Cures Rare Bachmann-Bupp Syndrome
Dr. Fajgenbaum shares an incredible story of Bachmann-Bupp syndrome, a rare genetic condition where children are wheelchair-bound. A drug originally developed for African sleeping sickness, DFMO, acts as a covalent binder to the overactive enzyme (OCE1) in these children, allowing them to lead significantly more normal lives if treated early.
Proactive Healthcare: No One Should Suffer Unnecessarily
Dr. Fajgenbaum emphasizes the critical need for proactive healthcare and widespread information dissemination. He argues that no one should suffer from preventable or treatable conditions like Bachmann-Bupp syndrome, breast cancer, or heart disease if effective, repurposed drugs are known, pushing for a system where crucial information isn't left to chance.
The Discovery That Saved His Life: Sirolimus for Castleman Disease
After his fifth near-death experience, Dr. Fajgenbaum intensely analyzed his own biological samples. He discovered that a communication line in his immune system called mTor was in 'overdrive.' Taking this data to his doctor, he suggested trying an mTor inhibitor, Sirolimus (Rapamycin), a drug approved for organ transplant rejection but never used for Castleman's. Despite the high, immunosuppressive dose, Sirolimus put him into remission, a state he has maintained for nearly 12 years, saving his life after doctors had given up hope.
The 'Darker Sides' of Drug Patents: Why Repurposed Generics Are Overlooked
Andrew Huberman and Dr. Fajgenbaum explore the complex incentives within the pharmaceutical industry. They explain how drug companies are heavily incentivized to find new uses for existing drugs to renew patents and keep generics off the market, often through slight formulation changes rather than exploring truly new diseases. This system, while sometimes beneficial, creates a 'darker side' where new, life-saving uses for generic drugs are rarely explored due to a lack of financial incentive, leaving 14,000 diseases without treatment.
Bridging the Healthcare Gap: The Need for an Integrated Medical Database
Andrew Huberman discusses how personal 'knowledge networks' significantly impact healthcare outcomes, noting that most people lack access to leading experts. He proposes a straightforward solution: an integrated, publicly accessible database where individuals can input symptoms and family history to discover existing prescription and non-prescription treatments, understand drug overlaps, and connect with specialists, arguing that such a resource is essential in modern times.
How Football Taught Dr. Fajgenbaum to Fight for His Life
Andrew Huberman asks Dr. Fajgenbaum if his athletic background, specifically playing football, contributed to his incredible drive and resilience in fighting his disease. Dr. Fajgenbaum confirms that his 10-year mission to become a Division I college quarterback instilled a constant drive and taught him about loss, resilience, and enduring physical pain. He connects these experiences to his ability to withstand the 'worst pain imaginable' during his illness.
The Tragic & Triumphant Tale of Thalidomide: From Birth Defects to Cancer Cure
Dr. Fajgenbaum recounts the infamous history of thalidomide, initially causing severe birth defects when used for morning sickness. He then details its incredible repurposing decades later, first for leprosy and then for multiple myeloma, saving thousands of lives. He explains that its anti-angiogenic effect, which hindered limb development, is also key to its therapeutic action against these diseases, highlighting the complex nature of drug effects and the role of patent life in its varied applications.
The Future of Healthcare: A Personalized, Integrated Disease Database
Andrew Huberman emphasizes the current disorganization of scientific knowledge related to disease. He proposes an innovative, user-friendly database where individuals can input family history and symptom profiles to receive personalized insights on potential prescription and non-prescription treatments, including overlapping pathways with other approved drugs. This vision aims to democratize access to medical knowledge, moving beyond reliance on personal connections within the medical field.
The Power of Social Support and Living in 'Overtime' with Gratitude
Andrew Huberman emphasizes the critical role of social support in combating disease and general health issues, highlighting Dr. Fajgenbaum's 'amazing team' (family and loved ones). Dr. Fajgenbaum reflects on his 'overtime' experience—living for 11 years beyond expectations—and how it instilled a profound sense of gratitude. While the initial 'fear and clarity' of overtime may fade, he explains how physical scars serve as powerful reminders to remain thankful for every moment.
The Brain's Seat of Tenacity: The Anterior Mid-Singulate Cortex
Andrew Huberman reveals the neuroscience behind the 'hope, action, impact' circuit, explaining Dr. Joe Parvizi's discovery of the anterior mid-singulate cortex as the brain region associated with tenacity and the will to lean into challenges, linking it to success in overcoming obstacles.
How Colchicine Was Repurposed to Prevent Heart Attacks
Dr. Fajgenbaum explains how a researcher hypothesized colchicine's anti-inflammatory properties could reduce heart attack risk, but faced funding challenges for trials due to the drug's age. By slightly altering the dose, they secured FDA approval, demonstrating a significant reduction in heart disease risk for specific patient groups.
The Hidden Tragedy of Unfunded Drug Repurposing
Dr. Fajgenbaum highlights the systemic flaw where effective drug repurposing often goes unfunded for large-scale trials, leading to a "tragedy" where potentially life-saving treatments remain obscure, and patients unnecessarily suffer heart attacks because the system didn't facilitate proving an existing drug's new benefit.
From Delivering Babies to Organ Failure: David Fajgenbaum's Sudden Illness
Dr. Fajgenbaum recounts his harrowing personal health crisis during medical school, where he rapidly went from a high point of delivering babies to experiencing enlarged lymph nodes, extreme fatigue, abdominal pain, and eventually, multiple organ failure, including temporary blindness and gaining 100 pounds of fluid, without a diagnosis.
Receiving Last Rites and the Castleman Disease Diagnosis
Dr. Fajgenbaum describes the terrifying 11 weeks without a diagnosis, during which his condition worsened to the point of receiving last rites at age 25. He details how a pathologist finally identified Castleman disease, an atypical lymphoproliferative disorder where his immune system became hyperactive, producing cytokines that attacked and shut down his vital organs.
The Will to Live: How Super-Agers Maintain Brain Volume and Positive Anticipation
Andrew Huberman connects the anterior mid-singulate cortex to 'superagers' who exhibit remarkable longevity and a strong will to live. These individuals maintain brain volume in this area and report high levels of positive anticipation, contrasting sharply with symptoms of depression.
Applying the Hope-Action-Impact Circuit: A Navy SEAL's Approach to Challenges
Andrew Huberman provides actionable advice on how to apply the 'hope, action, impact' circuit to daily life, drawing parallels to a Navy SEAL's strategy for tackling challenges: shorten the horizon, maintain a forward center of mass, and focus on duration, path, and outcome.
The Japanese Drug for Castleman's His Doctors Didn't Know About
Dr. Fajgenbaum reveals that a drug called Tossalismab, effective for Castleman disease, was developed and approved in Japan but unknown to his US doctors due to information asymmetry. He shares the remarkable story of its discoverer, Dr. Kazu, who self-administered the new monoclonal antibody to prove its safety before giving it to patients, highlighting the challenges of drug repurposing and knowledge gaps in global medicine.
The Irony of Feeling Better on "The Worst Chemo"
Dr. Fajgenbaum describes his relapse after initial chemotherapy and the desperate need for a combination of seven "worst chemos" to achieve remission. He shares the profound irony that, despite the harshness of the treatment, he felt better with every dose because the chemotherapy was suppressing his overactive immune system, which was actively killing him, leading to his eventual discharge and immense gratitude for being alive.
The Reality of Physician Knowledge: Random, Peacemeal, and Often Incomplete
Dr. Fajgenbaum and Andrew Huberman discuss the limitations of how physicians access and stay updated on medical literature. They highlight that doctors often rely on random, piecemeal information, unable to review the vast amount of relevant research, leading to inconsistent "opinions" even among specialists, rather than systematic, data-driven decisions.
Nobel Laureate's Secret to Neuroprotection: Nicotine
Andrew Huberman shares a fascinating anecdote about a Nobel Prize-winning neuroscientist who chews Nicorette daily, believing nicotine (separate from smoking) offers protection against Alzheimer's and Parkinson's by safeguarding dopaminergic and cholinergic neurons.
The 'Hope, Action, Impact' Circuit for Overcoming Challenges
Dr. David Fajgenbaum shares his personal 'hope, action, impact' circuit, where hope for a better future drives action, leading to positive impact, which in turn fuels more hope, creating a powerful feedback loop for resilience and progress.
When Doctors Said 'There's Nothing More': David Fajgenbaum's Resolve to Find His Own Cure
After multiple relapses and being told by the world's experts that there were 'no more options' for his life-threatening Castleman's disease, Dr. Fajgenbaum describes a moment of clarity. He realized that while seven chemotherapies had saved his life temporarily, there could be an eighth drug, or a ninth, not yet tried. This profound realization ignited his determination to dedicate his life to finding repurposed drugs that could help him and other patients.
The 'Overtime' Awakening: Calling Plays From Near Death
After trying two potential drugs that failed, Dr. Fajgenbaum experienced his fifth near-fatal relapse. He recounts the harrowing experience of saying goodbye to his family and feeling life fade away. Miraculously, he began to wake up two days later, experiencing what he calls 'overtime' – a profound joy and sense of urgency. Immediately, he started 'calling plays' like a quarterback, instructing his family to gather critical samples to continue his research, embodying an incredible drive to find a solution.
Taking Agency in Your Health: Beyond Just What Your Doctor Tells You
Dr. Fajgenbaum highlights the critical role of patient agency, especially when facing severe diseases. He explains that with 4,000 FDA-approved drugs, many have untapped potential for other conditions. He advises patients to actively seek out disease organizations, leading experts, and to consistently ask questions about alternative treatments or drugs used elsewhere, rather than passively accepting initial diagnoses or treatment plans.
Surprising Uses: Aspirin for Cancer & Viagra for Pediatric Lung Disease
Dr. Fajgenbaum reveals lesser-known applications of common drugs, such as aspirin's role in reducing colon cancer recurrence and Viagra's life-saving repurpose for a rare pediatric lung disease. He also mentions Cialis's initial use for prostate health, illustrating how drugs often have multiple, unexpected benefits beyond their primary approved indications.
From 'Out of Options' to a Life's Mission: David Fajgenbaum's Journey to Drug Repurposing
Dr. David Fajgenbaum recounts the devastating moment his doctors declared him out of options for his life-threatening disease. This pivotal experience ignited his determination to challenge conventional medical thinking, leading him to dedicate his life to finding new uses for existing drugs and advocating for patient agency, driven by the belief that no one should suffer if a readily available drug could help.
Three Pillars for Surviving Extreme Pain and Challenges
Dr. Fajgenbaum shares three critical lessons he learned during his six-month ICU stay, facing excruciating pain and near-death experiences. These pillars for overcoming challenging situations are: 1) a clear vision for the future, 2) drawing strength from family and loved ones, and 3) the power of focusing on 'one more minute, one more hour, one more day' when faced with seemingly insurmountable long-term suffering. He illustrates this with a poignant story of his sister urging him to 'Just breathe, Dave. Just breathe.'
The Unused Potential of Lidocaine: A 29% Reduction in Breast Cancer Mortality
Dr. Fajgenbaum reveals astonishing data from a large trial in India: injecting inexpensive lidocaine around breast tumors before surgery led to a 29% reduction in 5-year mortality, yet this practice has seen little global uptake. He explains this 'mind-blowing' oversight is due to the lack of incentive for generic drugs, as no entity profits from promoting new uses for a decades-old, pennies-per-injection medication, despite its immense potential to save lives.
From 'Out of Options' to 9-Year Remission: The Angiosarcoma & Pembrolizumab Breakthrough
Dr. Fajgenbaum shares the incredible story of Michael, a patient with metastatic angiosarcoma who was told he had no options. His lab, through a simple PubMed search, found a three-year-old study indicating a PD1 inhibitor might be effective. Treating Michael with Pembrolizumab led to a 'transformative' 9-year remission and changed clinical practice for angiosarcoma, demonstrating that life-saving insights often exist as 'breadcrumbs' in published research, awaiting translation to patients.
A Son's Promise: Dedicating Life to Finding Cures
Dr. Fajgenbaum recounts the devastating news of his mother's terminal brain cancer at age 18, which completely altered his life's trajectory. He shares the profound moment he promised his dying mother he would dedicate his life to finding treatments, and her final words, "unconditional love," solidified his mission.
"Chiquita Banana Lady": Finding Humor and Agency in Brain Surgery Recovery
Dr. Fajgenbaum shares a poignant and humorous story about his mother's recovery from awake brain surgery for glioblastoma. Despite the severe and invasive procedure, his mother, upon seeing her family, pointed to her bandaged head and quipped "Chiquita banana lady," demonstrating incredible agency, resilience, and a powerful lesson in finding joy and connection even in the face of grave illness.
How to Find Hidden Cures: Connecting with Experts & The DADA2 Story
Dr. Fajgenbaum provides actionable advice for individuals seeking information on existing drugs for their ailments: connect with disease organizations, identify world experts, and persistently ask questions about alternative treatments. He powerfully illustrates this need with the heartbreaking and inspiring story of DADA2, a rare condition causing strokes in children, where a life-saving TNF inhibitor treatment was known by some doctors for years but not widely disseminated, leading to preventable deaths.