My doctor explained to me that we were out of options. He said, David, we've tried everything. We tried these chemotherapies. We tried this one experimental drug. There's nothing more that we can do. There was a few-minute period where my dad and my sisters and my girlfriend around me, and we were just bawling our eyes out.

This is the world's expert. And I kept probing him, like, is there any cell type or signaling pathway? Is there something we can target? Like, and he said, David, there's nothing. Is there anything in the early stage develop? David, there is nothing. I heard what he was saying, but then I thought to myself, you just gave me seven chemotherapies that were made for lymphoma and my multimyeloma.

And they've saved my life now three times. They're not, it's not long-term. Like, I know I keep relapsing, but, like, if these seven chemotherapies are working, how do we know there's not an eighth chemotherapy or a ninth drug for something else? Like, you can't tell, we haven't tried all 4,000 drugs.

We've just tried the drugs that maybe we've thought to try. And so I just locked in right then, and I turned to my family, and just sort of wiped away my tears and said, I'm going to dedicate the rest of my life, however long that's going to be. It might be a couple days.

Maybe it'll be a couple months. But however long I've got to trying to find out, is there a drug out there that could help me and other patients with my disease that's made for another condition? I just believe that the 4,000 drugs we have today should help all the patients who can benefit from them, period.

Like, no one should suffer if there's a drug at your CVS that could help you. Welcome to the Huberman Lab Podcast, where we discuss science and science-based tools for everyday life. I'm Andrew Huberman, and I'm a professor of neurobiology and ophthalmology at Stanford School of Medicine. My guest today is Dr.

David Fagenbaum. Dr. David Fagenbaum is a professor of translational medicine and human genetics at the University of Pennsylvania. His work focuses on finding novel cures to both rare and common human diseases by using drugs and other treatments that already exist and that are approved for use in humans for other purposes.

As it turns out, most approved drugs impact at least 40 different pathways and mechanisms across the human brain and body, but these drugs are generally approved for use in just one or two of those pathways. David shares with us the many commonly unknown yet powerful benefits of drugs that are already approved for things like heart health, combating cancer, neurodegeneration, and more.

From his own near-death experience with Castleman's disease, David discovered that the medical profession already has in hand excellent treatments and perhaps even cures for many of the childhood and adult diseases that the medical profession deems uncurable or untreatable. In addition to running his laboratory where they search for novel treatments and cures using already approved drugs, David has started a not-for-profit called Every Cure, which helps people find treatments and cures to diseases that the medical field has essentially deemed untreatable.

And that work has already saved countless lives. Our discussion today is about how to navigate your health journey and how to approach the treatment of any illness that you or a relative may face. It's also about the fact that while the fields of medicine and science are truly incredible and well-intentioned, they do have a giant blind spot built into them, which is that many effective treatments and in some cases cures exist to diseases that we are told are hopeless to treat.

And that even the best trained and well-meaning MDs are often unaware of those treatments, not because they are lazy or that they have some other agenda, but simply because of how medications are studied, patented, and categorized. As you'll soon learn, Dr. Fagenbaum is on a mission to educate doctors, scientists, and most importantly, you, the general public about these facts.

He has lived them directly. He's an MD who got very sick with what he was told was a terminal disease. And when the existing system left him at a cliff, he went about curing that disease using old medications in new ways. And he is now helping others who need to do the same.

Before we begin, I'd like to emphasize that this podcast is separate from my teaching and research roles at Stanford. It is however, part of my desire and effort to bring zero cost to consumer information about science and science related tools to the general public. In keeping with that theme, today's episode does include sponsors.

And now, for my discussion with Dr. David Fagenbaum. Dr. David Fagenbaum, welcome. Dr. David Fagenbaum: Thanks so much for having me. These days, people are very concerned about their health, even if they're healthy. And I think the reason for that is ever since 2020, I think people have started to realize that they need to do more self-advocacy in terms of their health, whether or not it's behaviors to take care of their health, learning how to explore medical and health information online more effectively.

No one knows who to trust. And yet people are realizing that they are a critical element in their health. And should they encounter challenges to their health, they realize they can no longer be passive participants and just go to their doctor, that doctors are human too. So you have a very unique health story and we'll get into that.

But maybe we just start off by educating people a little bit about some of the common misperceptions in order to give them more sense of agency about what they can do. One of the things that you've been very vocal about is that you believe through experience and observation that many of the treatments or even potential cures for the things that challenge people may already exist in the form of medicines that are prescribed or available, maybe even over the counter.

But that people, including doctors, are not aware of that. Could you just elaborate on that? What we're basically saying is the answers may already be here. Sure. Well, first of all, I love that you're talking about agency in health and in medicine. Because I think oftentimes we talk about agency, you know, I can get a good night's sleep or I can exercise and eat well in the sense of wellness.

But oftentimes when people get really sick with a horrible disease, whether it's cancer or Castleman's, feel like, well, we're just going to do whatever our local doctor tells us to do. But you're right. I think that there's so much more that we can do and there's so much agency that we can take.

And part of it, to your point, is that there are drugs that we have. There's 4,000 FDA approved drugs that are approved for about 4,000 diseases. But we know from laboratory work and also from clinical trials that many of those drugs can be used in more diseases. But unfortunately, the system really isn't set up to find new uses for old medicines.

And so that's the work that I do. But I also think it gives all of us really a sense of responsibility that if we're diagnosed with a bad disease, that we find out what's the disease organization advocacy group. Maybe they're aware of a drug being used in one part of the world, but others aren't.

Who's the leading expert? Can you go drive to see the leading expert? And can you make sure that once the expert tells you what to take, you ask questions like, is there potentially something else? Yeah. I think of aspirin, for instance. Yeah. Most people think of aspirin as a pain reliever.

Yeah. Aspirin is now used as a way to offset heart attacks for its blood thinning effects, among other effects. Just off the top of your head, I'm not trying to test you here. You're the MD, I'm the PhD, as we were talking about before, I'm not going to test you on medicine.

I'm not equipped to. But are there other uses for aspirin that we perhaps haven't heard of, or similar drugs that might surprise people? Yeah. Aspirin also has been shown to reduce risk of recurrence of colon cancer. Particularly individuals with colon cancer have a mutation actually in the mTOR pathway.

But because it's aspirin, because it's sort of widely available and it doesn't have maybe the same sort of system behind its use, it's really not actually utilized by all the patients that have colon cancer to reduce the risk of recurrence of colon cancer. That's sort of mind-blowing in itself.

There are other great examples. Many folks have probably heard about how Viagra was repurposed from heart disease. It's well-known use. People are aware of erectile dysfunction, but most people don't realize that it's also been repurposed for a rare pediatric lung disease. Kids were dying because they weren't getting enough blood flow to their lungs.

And if they take Viagra, they can actually get blood flow to their lungs and live full lives on Viagra. And that fortunately was discovered early on in the patent life of Viagra. So there was really a way to push it forward. A lot of times these happen after drugs are generic.

Isn't it that the cousin of Viagra, Cialis, was initially Tadalafil used to encourage prostate health, circulation to the prostate. And then only later was it discovered to have these other effects related to sexual function. That's right, yeah. And, you know, we talked about the side effect of a drug.

It can be bad or can be good. We were chatting earlier, you know, the average small molecule is a drug that's approved for a condition, combined between 20 and 30 different proteins in the body. So we call a drug, you know, we say it does one thing, but actually it's doing a lot of other things in the body.

And unless that drug company began working on it early on for that condition, oftentimes those insights and those other roles for the medicine just fall through the cracks. So the idea that a drug is useful for other things aside from what it's best known for is seldom discussed, whereas side effects are being discussed more and more nowadays.

Tell us about lidocaine. Sure. This is fascinating. Sure. So, yeah, I couldn't believe it when we came across this. So I run a nonprofit called Every Cure. We scan the world's knowledge of every drug and every disease to find new uses for the medicines we have. And when we came across lidocaine, we were just sort of blown away.

So lidocaine, of course, the numbing medicine you get if you go to the dentist and, you know, it's used all over the body for numbing all kinds of things. There's interesting data, actually, a large trial that was done in India of 1,600 patients where women who had localized breast cancer, if they had lidocaine injected around the tumor before surgery, eight to 10 minutes before surgery, there was a 29% reduction in mortality of five years versus those who did not have lidocaine injected.

Now, lidocaine is already going to be used during the surgery. It's used at the site of the incision. It's widely used, you know, in so many cases. And what's so interesting, it was published in a great journal, the Journal of Clinical Oncology, yet there's still been barely any uptake all around the world.

And so this is just sort of another example for us for why you've got to have an entity that's looking for these great opportunities and then actually doing the work to make sure that they get into patients. Because there's close to no downside of something like lidocaine. And if the upside is as high as a 30% reduction in mortality, I don't know how it's not being used all over the place.

Is lidocaine an expensive drug? It's a very inexpensive drug. It's, you know, pennies in injection. And that doesn't mean anyone's hiding lidocaine. I'm of the belief that drug companies do such important work to develop brand new drugs. And they're so good at it. They do a great job getting those drugs to be used for the uses that they're intended for.

And it's no one's fault. But once that drug becomes generic, like lidocaine has been generic for decades, that means that there's a number of other companies that make the exact same drug. And the profit for each of those doses becomes close to, you know, pennies in injection. And so, again, it's not that anyone's hiding it, but it's just that no entity is incentivized to actually go call on doctors and say, "Hey, did you do the lidocaine before your surgery?" Or to like to really push to get them into guidelines.

And I will say this was a really major study, this study that was published or that was done in India. It was published in a great journal. There's interesting laboratory data. But we at EveryCure actually feel responsible to better understand the potential mechanism for how it might work and also to review the evidence wholly before we actually go out and start, you know, encouraging everyone to do it.

So there's still steps that have to be taken. But our belief is that when you come across something, you know, that looks promising like this, we need to have some group that's actually pushing and pushing to make sure that it actually gets to patients once you feel comfortable with the data.

I'd like to take a quick break and acknowledge our sponsor, Eight Sleep. Eight Sleep makes smart mattress covers with cooling, heating and sleep tracking capacity. One of the best ways to ensure a great night's sleep is to make sure that the temperature of your sleeping environment is correct. And that's because in order to fall and stay deeply asleep, your body temperature actually has to drop by about one to three degrees.

And in order to wake up feeling refreshed and energized, your body temperature actually has to increase by about one to three degrees. Eight Sleep automatically regulates the temperature of your bed throughout the night, according to your unique needs. Eight Sleep has just launched their latest model, the Pod 5, and the Pod 5 has several new important features.

One of these new features is called Autopilot. Autopilot is an AI engine that learns your sleep patterns to adjust the temperature of your sleeping environment across different sleep stages. It also elevates your head if you're snoring and it makes other shifts to optimize your sleep. The base on the Pod 5 also has an integrated speaker that syncs to the Eight Sleep app and can play audio to support relaxation and recovery.

I've been sleeping on an Eight Sleep mattress cover for over four years now, and it has completely transformed and improved the quality of my sleep. If you'd like to try Eight Sleep, go to eightsleep.com/huberman to get up to $350 off the new Pod 5. Eight Sleep ships to many countries worldwide, including Mexico and the UAE.

Again, that's eightsleep.com/huberman to save up to $350. Today's episode is also brought to us by Rora. Rora makes what I believe are the best water filters on the market. It's an unfortunate reality, but tap water often contains contaminants that negatively impact our health. In fact, a 2020 study by the Environmental Working Group estimated that more than 200 million Americans are exposed to PFAS chemicals, also known as forever chemicals, through drinking of tap water.

These forever chemicals are linked to serious health issues such as hormone disruption, gut microbiome disruption, fertility issues, and many other health problems. The Environmental Working Group has also shown that over 122 million Americans drink tap water with high levels of chemicals known to cause cancer. It's for all these reasons that I'm thrilled to have Rora as a sponsor of this podcast.

I've been using the Rora countertop system for almost a year now. Rora's filtration technology removes harmful substances, including endocrine disruptors and disinfection byproducts, while preserving beneficial minerals like magnesium and calcium. It requires no installation or plumbing. It's built from medical grade stainless steel and its sleek design fits beautifully on your countertop.

In fact, I consider it a welcome addition to my kitchen. It looks great and the water is delicious. If you'd like to try Rora, you can go to Rora.com/Huberman and get an exclusive discount. Again, that's Rora, R-O-R-R-A.com/Huberman. There are a couple avenues that we could explore given what you've said so far, but the one I'd like to drill into a bit is this thing related to drug companies and patents.

I don't want to set up the idea that everything is conspiratorial. And yet years ago, when my laboratory was working on eye diseases, glaucoma in particular, I spent a lot of time around people working at companies that develop drug treatments for eye diseases. They've developed great drugs for the treatment of over vascularization of the eye, for instance, that can cause blindness or it's related to some blinding diseases.

And I learned that many of these drugs go to market. They are quote unquote blockbuster drugs. People, symptoms improve. These drug companies make a lot of money. And then the patent is headed toward expiration. And at that point, the cost of the drug drops markedly. So the drug companies are heavily incentivized, I learned, to find new uses for that drug, to renew the patent under this new application, to basically keep the generics away.

And on the one hand, it makes sense because the research and development for a drug is exceedingly expensive. And so if they can repurpose a drug and maintain the patent for two diseases, essentially, one drug, two diseases, this is kind of the bread and butter of how drug companies get and remain very wealthy.

It has two, what I consider kind of darker sides to it. One is that the generic cheaper drugs don't arrive on market for a much longer period of time. The other side of the coin, however, is that, you know, people suffering from a different disease now can take this drug.

But that second darker piece is that drug companies are not very incentivized to go look for new molecules to treat new conditions. They are heavily incentivized to use old molecules to treat new conditions and maintain control. There's a lot in this statement, but my understanding is this is how it works.

And so how do you reconcile that? I mean, how is it that we should be exploring existing drugs for new conditions, but do it in a way that's really driven toward curing and disease as opposed to just kind of finding a new purpose so we can keep the generics out for a while?

Yeah, it's such a good question. So you're absolutely right that as drugs begin to reach their patent cliff, oftentimes the dose might be changed slightly, the formulation might be changed slightly to create new intellectual property. So that way, this sort of new version can be used in that same initial disease.

which to your point, there's, you know, I wouldn't say pros and cons. There's, you know, side effects of that sort of a system. But what is pretty clear is that companies will typically not, as it's getting close to patent exclusivity, find a new disease to go after with that drug.

It's usually the same disease, it's just a new formulation. So that way they can keep working that disease. And what that means is that though that drug might be able to be used for a different disease, that's rarely explored. And so especially to your point, once it's generic, I mean, all of research and development discontinues.

And even I mentioned earlier that there's 4,000 FDA approved drugs, they work for 4,000 diseases, that's incredible. But there's still 14,000 diseases that don't have a single treatment right now. And of the 4,000 drugs we have, 80% of them are already generic, which means that there is no incentive to find a new use for those medicines.

So like, every time I walk past the CVS, all I think about is how many drugs are in there that are used for one condition, but could actually help so many more kids or adults with other conditions. And we're hearing a lot these days about lithium as a potential protectant for Alzheimer's or other forms of dementia.

I don't know that the data are so solid that I'm ready to run out and take lithium. So I'm not suggesting that to anybody. But I know a few psychiatrists that tell me for years, they've been taking low dose lithium for a couple months out of the year, based on their understanding of the data.

So you've got doctors doing things, people don't often talk about this, but doctors often will do things that based on their read of the literature that they're not talking to their patients about, because they're not in a position to do it ethically. There's too much liability there. Where and how should the typical person, without any training in medicine or science, or even a little background in science, go to find information about existing drugs, generic or otherwise, that could help them treat their ailments, be it a skin condition or something as serious as cancer.

What I'd recommend is the first is to make sure that you're connecting with whatever the disease group is for your condition. They oftentimes are so well connected physicians all over the world, they hear about what things are being tried. So connect with whatever your condition, whatever that disease organization is.

Dr. Justin Marchegiani: Could you explain disease organization? Dr. Justin Marchegiani: Sure. So like the Castleman Disease Collaborative Network is the group that's come together to support Castleman's patients. And to physicians and researchers, there's an ALS Association, for example. There's Michael J. Fox for Parkinson's disease. So find that group that has coalesced around your condition, because they'll oftentimes have, to your point, understanding about, "Hey, I heard this one patient's using this one thing." So Dr.

Justin Marchegiani: I'd go there first. The second is I would figure out where is the world's expert? Who is that person that really is the guru? They'll oftentimes have insights on these things. And then the third is to really keep asking questions. So like even when they say this is the first thing that's recommended, well, is there something else that's like used somewhere else?

And I'll share one example of this. It's a bit heartbreaking, but also really powerful and informative. And that's that there's a rare condition called data2. Basically, kids are born with a mutation in a gene that results in them having dozens and dozens of strokes from the time they're born until they usually pass away in their teenage years because of the accumulated effect of literally dozens of strokes.

It's horrible. Well, about 20 years ago, a doctor apparently was treating a patient with data2 and also treating a patient with a form of vasculitis and treated that patient with vasculitis with what's called a TNF inhibitor. It inhibits this one cytokine called TNF. And he apparently had left TNF inhibitor in his vial.

And he was like, "You know what? We've got this kid over here having all these strokes. Why don't I just try what I've got in this vial in this kid?" Well, the kid stopped having strokes. And that was amazing. And so this doctor, the next few patients he had with data2, he treated them for their strokes.

But about 10 years went by. Meanwhile, hundreds and thousands of kids around the world are dying from data2 where the word wasn't being spread until this amazing doctor named Chip Chambers sadly had two children born with data2. And he started looking around to figure out and learned about, oh my gosh, TNF inhibitors.

I was honored to be able to help Chip and his team to basically bring data together on the effectiveness of TNF inhibitors, also even come up with treatment guidelines for how do you treat data2. And it turns out that if you start kids on a TNF inhibitor, they stop having strokes all over the world.

Literally, it's a life changer. And so the reason I share this as an example is that the world knew, someone in the world knew that you could save kids lives with a TNF inhibitor, but the world didn't know. And we hadn't gotten the word out about it. And to me, that's so heartbreaking.

It's almost like a travesty. It's one thing if you have a horrible disease and everyone dies from it and there's nothing out there. But I think it's so much more heartbreaking when you think that, oh my gosh, there was something there. We just, we as a system, hadn't done the work to make sure people get the medicine.

Yeah, I think it's a harsh reality that one's knowledge network really has a big impact on outcomes to disease. I mean, I sit surrounded by MDs and PhDs and people working on disease and treating disease. And I'll tell you, there's no question in my mind that, because I've experienced it when a friend's spouse or kid is dealing with something.

I'm just one example of somebody who knows who to call, because I don't know the answer, but I know who might know the answer. And within two or three calls, that person is in touch with somebody who is in communication with the five or six people who are best at this around the world.

But most people don't have access to that. I mean, it's one of the reasons I started this podcast, frankly, to get people like you on here, people like Eddie Chang, who's a lifetime friend and chair of neurosurgery at UCSF. Like I would say, may you never need his help.

Yes. Right. You know, but these are the people that I call when friends have questions about things unrelated to neurosurgery, for instance. So it seems to me there's a pretty straightforward solution that in addition to these groups that are centered around certain diseases, there should be databases. There should be ways that people can not just go online and ask a question, but go to a database and say, you know, I was just diagnosed with, or I'm having symptoms that are the following.

And what are the existing prescription and non-prescription meds known to treat this? What are the side effects? But also what are the potential pathways that overlap with other approved drugs that are prescription or over the counter? And then it should feed into a pipeline of how to get a hold of the people that could help treat that.

It should be that straightforward. I mean, this is 2025. I mean, there's no reason why people should have to know somebody in the medical or scientific field at a major institution in order to be able to navigate this. I totally agree. And I think that the more I've got into this, the more surprised I've been that there hasn't been something like that.

This nonprofit I mentioned every cure. So we use this, they're called biomedical knowledge graphs, basically mapping out what the world knows about human biology. We use an AI platform and machine learning models to quantify how likely every drug is to treat every disease. And then we start at the top to go, you know, what match looks promising.

We've got nine active programs. And from those, we're moving them forward to reach patients. And the idea is that, you know, let's hope all nine of them end up being effective in helping patients. That's sort of the start of this hopefully master list of additional uses for medicines that we already have.

But to your point, it's not just that they are speculative, but really that the work's been done to really prove that they actually work. I can't help but ask of some other examples of drugs that have been shown to treat things other than what most people associate that drug with.

Sure. A few come to mind. So the first one's thalidomide. You probably have heard about the horrible birth defects that thalidomide caused 50 plus years ago. Originally designed as an anti-miscarriage drug. Well, it was originally designed as anti-nausea for pregnant women. So the thought was that it could help them with their nausea, but it ended up causing horrible birth defects.

I see. Children were born without limbs and so it was taken off the market. But then about 20 years later, researchers figured out that it could be effective for leprosy. So it's FDA approved for leprosy. And then what's crazy is that shortly thereafter, it got FDA approval for multiple myeloma, a rare or somewhat rare hematologic blood cancer.

And the reason that it can work for leprosy and multiple myeloma and also the reason that it causes birth defects is it has a major anti-angiogenic effect. So it reduces blood vessel growth. So in the same way that you need blood vessel growth to grow limbs, you also need blood vessels or you need over production or increased blood flow for multiple myeloma cells to survive and also in leprosy.

And so the same compound that causes birth defects, helps treat leprosy, also treats multiple myeloma. It saved thousands and thousands of lives in multiple myeloma patients. Again, the reason that that in particular has been utilized in multiple ways was that it had a full patent life when the work was first begun for leprosy and then myeloma was discovered shortly thereafter.

But if a drug like thalidomide was discovered for leprosy and then 20 years later someone figured out it could be useful for multiple myeloma, patent is gone. And so there wouldn't have been an incentive to then figure out that oh thalidomide could also be useful for multiple myeloma. The list sort of sadly goes on and on.

I mean 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 and for lung cancer and actually the work that we did in my lab I guess this is 2016 and it was actually simple work.

A patient came to us in 2016 with metastatic angiosarcoma which is a horrible form of cancer and his doctors told him that he was out of options and we did something really simple. We went on PubMed and looked for like angiosarcoma treatment. I mean it was that simple and we came across a paper from 2013 where a researcher had looked at five tumors from five different patients angiosarcoma and four out of the five tumors had increased expression of PD-L1 which is a marker that you might respond to a PD-1 inhibitor.

And so even though the paper was published in 2013 and this gentleman came to us in 2016 and of course hundreds of people had died in the previous three years, no one had ever actually tested whether a PD-1 inhibitor could be useful for angiosarcoma even though again it was just it was a laboratory study published three years earlier but no one had ever translated that insight into using it in a patient.

So we treated Michael as the first patient ever that we're aware of with a PD-1 inhibitor and he responded so incredibly well a couple things happened. One is that his doctors started prescribing it to all patients with angiosarcoma. It turns out it works in about 18 percent of patients so it was a uniformly fatal cancer within one year.

Now about 20 percent of people will live beyond a year and it can be really transformative. So it changed clinical practice for angiosarcoma. The other thing it did specifically for Michael is that it has put him into now a nine-year remission. Just last month he walked his daughter down the aisle on her wedding day in Nashville, Tennessee nine years after he was told that this is it.

And so these drugs are out there and sometimes there's even breadcrumbs. Like it didn't require any brilliance from my lab. We literally just had to find a study that was published three years earlier and that again is really what drives us with with this with this work now to say can we find all these breadcrumbs?

Can we put them together and can we make sure people actually benefit from all the great science that's being done all over the world that's actually translated into patients? Yeah it seems to me that PubMed and other sources of of science knowledge are great for stacking papers and and they're pretty decent in terms of how they're organized you know by keyword search.

I mean they're not perfect but you can find stuff. Yeah. And you get suggestions about related articles and somebody with a little bit of time and energy will get some degree of information there. But it seems to me that no one has really organized that the enormous database of information about science as it relates to disease.

It occurred to me a moment ago there should be a database where one can enter whatever knowledge they have about how old their grandparents were when they died and of what how old their parents are or were maybe they're alive maybe they're deceased any knowledge any any kind of family history this is the first thing a doctor would ask you if i come in and you're the md and if i say hey listen you know i've got like this swollen lymph node on the left hand side i don't i don't think you're going to say hey like go get it scanned you'll say any history of blank and blank in your family first thing right one should be able to do this from home and then enter any symptom profiles they might be having and with the appropriate cautionary notes get some ideas back about what might be going on and that might sound like oh this is people playing their own doctor but i'll tell you right now if i put in uh left armpit lymph node pain yeah or swelling into any online search engine it's going to tell me some of the worst possible outcomes so it's not like we need to shield people from potential outcomes but it seems to me that this should be pushed through an ai read of pubmed which already exists right most of the large language models are trained on the entire internet including pubmed and that it should point somebody in some actionable directions including which of these groups i meant to ask this earlier excuse me which of the various groups for a given disease is the best one yeah exactly like if somebody is kid you know god forbid has a has a blood cancer yeah which group do you go to is there a best one are these rated by anybody i mean i i'm not trying to throw our arms around all of medicine here and all of the problems in the world but it seems to me that all of this is tractable someone just needs to get organized about the databases i completely agree i think that there's such randomness to to health care into our biomedical research system i think that's probably maybe the the most heartbreaking part of this all is that because it's so random you know michael gets a drug and he walks his daughter down the aisle nine years later and a bunch of other people don't get a drug and they they aren't alive and so i i love the idea of that centralized database i think that there's a company called open evidence which is trying to to basically create a gpt but for health care um i don't know if it's i don't think it's it's to where you described it where you can really put in your personal family information and get answers but i'm hopeful that others will um you know the role that i see our work and and my work fitting into that is basically finding as many of these connections and proving them out in the lab and in clinical trials as possible so that way when you type in your disease and your situation that that drug that we worked on you know rises at the top because it wasn't just a connection in pubmed but it was a connection in pubmed that we've added in the lab and we did the trial to prove that it works yeah it's kind of wild that on a completely different end of the spectrum um you know recently everyone's talking about creatine creatine creatine creatine okay i'm taking creatine since my teens because i heard back then that it would help make me stronger it'll make you stronger now people are talking about creatine for women for men for older people under conditions of sleep deprivation for cognitive support let's face it the effects while documented are fairly mild for cognitive support but they're there and this is not being touted as a treatment for like dementia although it might help offset some minor dementia or something like that i don't know but the point is that people are talking about it it's in the news it's covered all the time but we really should be talking about or also talking about drugs like aspirin that can be very useful for potentially for colon cancer and heart attack not just for pain and all the other examples that are out there yeah but i think there's this fear that if you talk about a drug that people are just going to start taking it yes uh as an uh an attempt at a prophylactic yeah right and i think that um there's a lot of um caution around that for understandable reasons but i want to know i just turned 50 i want to know all the things that i could be taking to potentially offset heart attack because i'm already exercising and trying to get my sleep and doing all that stuff and then i can make a decision so where is the database of information about as a 50 year old male who does the following things to support his health no history of heart disease in my family that i'm aware of well what drugs are on the counter um or molecules that exist in behind a script from a doctor that could potentially extend my life i want to know that information yeah and what we're talking about creatine yeah so for once i'm i'm kind of like uh i'm not being disparaging of supplements but like it doesn't make any sense the conversation is skewed in in the wrong direction yeah i mean i think that what we're trying to do with with every cure and with our work is trying to start this conversation and keep the conversation going so that way you can go to your doctor with you know with x drug um you know i mentioned that we have nine active programs so on the one end of the spectrum really common is is our program with lidocaine and breast cancer where we're doing laboratory work we're also evaluating clinical data and i hope at some point in the future that the data is strong enough and if it is then we'll we'll work to to encourage every woman who's about to go in for breast cancer surgery to talk to their surgeon beforehand and say hey i want to make sure you do this instead of really empowering them in that way but all the way through even to the rarest of conditions there's a condition called bachman bupp syndrome where kids are born with a mutation that caused them to have elevated levels of an enzyme called oce1 and basically they're on feeding tubes they are wheelchair or bed bound unless you give them a drug that was made for african sleeping sickness which is a perfect covalent binder to oce1 so that enzyme that's too high in these kids african sleeping sickness medicine actually binds to oce1 and if you started early enough in life these kids get their feeding tube taken out they might be able to sit up they can even play with their siblings and so the reason i mentioned this is that there aren't that many people with bachman bupp in fact it's only been described in 20 kids which means there's probably hundreds of kids um because the medical uh literature is typically behind reality but let's say there's hundreds of kids at some point we're going to get the word out so that way you know we can find every kid possible you know with bachman bupp so they can get this this medication dfmo and so um that these are microcosms of what you're talking about which is that like no one should suffer from bachman bupp without being on dfmo no one should have breast cancer without having had lidocaine no one should be a healthy 50 year old man who might be able to have their risk of heart attack reduced it might be that colchicine is helpful for um for reducing your risk of heart disease but to your point how can we get this more proactively so we're not just sort of like hoping and waiting that all these random things line up we used to use colchicine in the lab so coaching is an interesting one so um colchicine uh is typically utilized for gout um it's this it's been around forever actually i learned that it's like 3 000 years ago was when it started being used um because uh gout often occurs in individuals who consume too much alcohol and so like apparently in like egypt 3 000 years ago some of the um wealthy people were drinking too much alcohol and somehow they figured out that this molecule uh colchicine of course i think it was a root at the time could be helpful for reducing gout um and we should fact check that that statement because i need i don't know the exact details but it's been around a long time if there were a database you just go to the database that's right you can tell where my mind's going yeah exactly so so colchicine's around forever it's been used for gout for many for decades um people have gouty arthritis they get these painful joints to give them colchicine it helps them out well a researcher a couple decades ago um had a hypothesis that because of its anti-inflammatory properties um and a few other properties of colchicine that it might be able to reduce the risk of heart attacks in people who've already had a heart attack or maybe in general but in particular people have already had a heart attack and um because it's been around forever they couldn't um they really couldn't raise the funding needed to do all the trials to prove it because um heart disease prevention trials are big expensive trials you got to follow people for years to prove they didn't get a heart attack versus people who did who got a placebo so they ended up changing the dose of that medicine of colchicine so it's a slightly different dose from the one that you use for gouty arthritis but it has a very substantial reduction in heart disease risk if you had a prior heart attack and in particular if you had a prior heart attack and you have diabetes a really really meaningful reduction so got fda approval for for that particular subpopulation but i mention it because if they hadn't changed the dose it would have been a paper that some academic would have published that i think colchicine could help and no one would have ever done the big trial and again that's sort of the tragedy here is that people are literally not having heart attacks right now because they're on colchicine but if not for someone figuring out a way to make the system work you know they would have had their heart attack we've known for a long time that there are things that we can do to improve our sleep and that includes things that we can take things like magnesium threonate theanine chamomile extract and glycine along with lesser known things like saffron and valerian root these are all clinically supported ingredients that can help you fall asleep stay asleep and wake up feeling more refreshed i'm excited to share that our long time sponsor ag1 just created a new product called agz a nightly drink designed to help you get better sleep and have you wake up feeling super refreshed over the past few years i've worked with the team at ag1 to help create this new agz formula it has the best sleep supporting compounds in exactly the right ratios in one easy to drink mix this removes all the complexity of trying to forge the vast landscape of supplements focused on sleep and figuring out the right dosages and which ones to take for you agz is to my knowledge the most comprehensive sleep supplement on the market i take it 30 to 60 minutes before sleep it's delicious by the way and it dramatically increases both the quality and the depth of my sleep i know that both from my subjective experience of my sleep and because i track my sleep i'm excited for everyone to try this new agz formulation and to enjoy the benefits of better sleep agz is available in chocolate chocolate mint and mixed berry flavors and as i mentioned before they're all extremely delicious my favorite of the three has to be i think chocolate mint but i really like them all if you'd like to try agz go to drinkagz.com slash huberman to get a special offer again that's drinkagz.com slash huberman today's episode is also brought to us by david david makes a protein bar unlike any other it has 28 grams of protein only 150 calories and zero grams of sugar that's right 28 grams of protein and 75 of its calories come from protein that's 50 percent higher than the next closest protein bar these bars from david also taste amazing right now my favorite flavor is the new cinnamon roll flavor but i also like the chocolate chip cookie dough flavor and i also like the salted peanut butter flavor basically i like all the flavors they're all delicious also big news david bars are now back in stock they were sold out for several months because they are that popular but they are now back in stock by eating a david bar i'm able to get 28 grams of protein in the calories of a snack which makes it very easy for me to meet my protein goals of one gram of protein per pound of body weight per day and to do so without eating excess calories i generally eat a david bar most afternoons and i always keep them with me when i'm away from home or traveling because they're incredibly convenient to get enough protein as i mentioned they're incredibly delicious and given that 28 grams of protein they're pretty filling for just 150 calories so they're great between meals as well if you'd like to try david you can go to davidprotein.com slash huberman again that's davidprotein.com slash huberman well i feel like we could spend hours going through the catalog of drugs for which uh these examples exist um and we may return to a few more but i'm putting in a strong vote for this database i know you're working hard on this i'd like to talk about your journey into this because you are not a typical doctor um i think that's apparent to people already uh you care very much about human health and treating human disease uh but you have a very unusual and interesting trajectory into medicine and i do believe it's helped lead you to this uh very unique orientation within the field of medicine and science so tell us that story and uh teach us about castleman's disease sure um well my story um i think really starts back when i was 18 years old and um i was a freshman at georgetown um we were talking earlier about i played football at georgetown that for me growing up that was my dream to be division one college quarterback that's all i could think about i was not quite as jacked as you but somewhere i saw a photo you were larger than i was yeah we'll put up a link to a photo i david was 230 you're taller than i am i'm six one so you're probably six two three six yeah i think you might be six three either that or i'm shrinking um and uh super large fit low body fat i mean you you look um you clearly you're a quarterback but you're large even for a quarterback i was yeah okay so you know that was my dream was you know i want to play college football and i got there and i was had been on campus at georgetown for a couple weeks and um i got a call that changed my life my dad called and and told me that my mom had brain cancer and uh andrew i went from like all i could think about was football and like you know i'm finally at this you know goal that i'd always set to oh my gosh this is just just changed everything my mom uh my mom and i were so close and i was heartbroken for uh glioblastoma brain tumors are uh uniformly fatal they're horrible um uh you know i was only 18 so i don't think i knew just how bad it was but i knew it was really bad and um watching her battle with cancer over the next 15 months um just changed everything in me um it it completely locked me in and i told her just before she passed away that i would dedicate my life to trying to find treatments for patients like her and um she she couldn't say many words um at the at the end but she said unconditional love those were the two words that she said when i told her i would do that and i was like all right i got to do this you know she she um you know she wants me to do it and for me i i sort of haven't been able to stop thinking about helping people like her from the moment that i started seeing this um horrible cancer um uh you know take her life in front of me and um and of course the promise that i made to her i also learned so much from her in watching her her battle against brain cancer i mean i'll just tell one one quick story um so i got that call from my dad i immediately came home to north carolina and within a few days she was having brain surgery to get the tumor resected and they did a surgery where um they put you to sleep to open up your skull and then they actually wake you up while your skull's open and um the reason for that which you're very familiar with is that as they're cutting out particularly in the left side of the brain cutting out parts of the brain tumor you want to be able to see where how far you want to go um you ask people to speak and sort of when they start slurring their speech you stop cutting and so they went through this whole surgery it was like a four and a half hour surgery cut out most of the tumor but not everything and um they you know woke her back up after after the surgery and um she was in the waiting area and we went back to see her and i remember my dad i've got two amazing older sisters my dad and i we um went back to see her and we were you know so nervous like is it going to be our mom who's going to come out it took out a lot of her brain um as part of the surgery and um so nervous and we walked back andrew and pulled the curtain back i'll never forget i saw my mom sitting there just about as far away as you are and she had a wrap around her head um bandages and she had this bulb coming out um that was collecting fluid and she looked at her at her she looked at us and she pointed up to her head and she said chiquita banana lady and we just burst into laughter she was saying she looked like the chiquita banana lady and like that for me was this incredible moment of just like taking agency back from this like horrible cancer like you just went through surgery but like you're going to find something to laugh about and something to get your family to laugh at and to show that like you're still there um and so that was sort of the the first of many lessons that i learned from my mom obviously in her health but also in her illness and so that set me on this journey which is okay i'm going to dedicate my life to trying to find treatments for patients like my mom i'm going to try to live um in in the way that she did and um i was sort of well on my way i um finished medical or sorry finished undergrad at georgetown i did a graduate degree at oxford and then i was a couple years into med school at penn when you mentioned castleman disease when i went from being totally healthy i shared earlier i won a bench pressing contest right around that time i was so healthy to being in icu with all my organs shutting down the story about your mom is a remarkable one uh my first thought when uh you mentioned the chiquita banana lady reference is that uh even though she was the patient it seemed like she was uh successfully taking care of all of you she was she was trying to take care of us yeah i know very little about her only what you shared but she sounds like a very impressive woman she was amazing i so appreciate you saying that yeah um that comes through so castleman's i've never heard of it who's castleman and uh these physicians like to name diseases after themselves um but my guess is that they're not the ones with the diseases they're the ones that discover the diseases correct that's right yep so benjamin castleman was a doctor in um boston at harvard he'd been getting these cases of patients that were thought to have lymphoma and they they appeared like they had lymphoma getting very very sick very quickly but when he looked under the microscope but then they didn't look like a typical lymphoma patient and so um maybe as i as i share you know sort of what my progression looked like i mean i was third year med student i just um finished uh an ob g on rotation i just delivered babies into the world which is sort of a peak moment in medical school and then within a couple weeks i noticed that i had enlarged lymph nodes in my neck i felt more tired than i'd ever felt um and you're tired in med school and grad school you know well but i was more tired than ever had horrible abdominal pain and i noticed fluid pooling around my ankles and this is so weird what's going on um but the fatigue got worse and worse and worse um and over the course of it really was just a couple weeks um i got so bad that i went i took a med school exam then i went down the hall to the emergency department i basically stumbled down to the er and just told them my symptoms and they ran blood work and um i remember my my doctor coming back and um and looking at me and saying david your liver your kidneys and your bone marrow are all shutting down we have to hospitalize you right away and i'm like what do you mean like i was just like i delivered a baby a couple weeks ago like how all my organs are shutting down and so they hospitalized me and i deteriorated really rapidly i had a retinal hemorrhage that made me temporarily blind in my left eye i gained a total of about 100 pounds of fluid because my liver and my kidneys stopped working you saw that picture where i just flew it everywhere um because of the multi-organ failure and um i needed daily translusions of red blood cells and platelets just to keep me alive i was on dialysis at the time as well so basically everything was shutting down and we had no diagnosis so we didn't know what it was my doctor some doctors thought it was lymphoma others thought maybe it was autoimmune disease others had no idea what it was um but over the course of about 11 weeks i got worse and worse and worse and at one point i was so sick that um i said goodbye to my my dad and my sisters and my girlfriend at the time caitlin and um a priest came in my room and read me my last rites when i was 25 years old fortunately right around the time um of having my last rites read to me which was really the end i mean i didn't didn't have more than a couple days left that's when the diagnosis came in of castleman disease um so basically a pathologist looked at my lymph node and they thought i had lymphoma they figured it was a really aggressive lymphoma which is a form of cancer but they looked at it and just like benjamin castleman did looked at it and said this doesn't look like lymphoma this actually looks different it looks like this thing called castleman disease which is basically um what we call it atypical lymphoproliferous disorder so it's kind of like lymphoma but it's got features that are more like an autoimmune disease and so basically your immune system becomes highly activated and starts attacking all your vital organs so the reason that all my organs were shutting down is because my immune system was producing cytokines and other factors that were were basically um shutting it down do you think that the um long hours of medical school plus being athletic they're very driven contributed to the autoimmune flare-up and we don't often discuss this but anyone that's dealt with an autoimmune issue even if it's like psoriasis or something um which can be very severe but in most cases it's kind of minor to you know they're over-the-counter things you can use i think but um it's associated with people who are pushing very very hard and and uh tend to pull long hours and and as a consequence the immune system understandably ramps up its activity and then goes past a tipping point where it starts attacking one's native tissue yeah it's funny no one ever asked that but it's the right question to ask and i think people are always sort of afraid to you know get into like the whys of these things happening to you i'm glad you asked because actually there was a paper that was published a couple years ago um i think it was in cell where mice that were sleep deprived like significantly multi-day sleep deprived what actually killed them was a cytokine storm due to their immune system producing all these cytokines like they actually so like because we know the sleep deprivation is deadly right you don't sleep enough you know this very well but again in these mouse studies this the actual thing that killed them was their immune system producing cytokines including interleukin 6 which is an important cytokine in castleman's um and by just trying a couple of medicines that basically block the production of some cytokines you could keep the mice alive longer really pointed this idea that it's sleep causing some disruption in immune balance causing excess production of cytokines causing death and and so um i don't know if you had you had you seen i i can share the paper with you it's it's pretty familiar with that one i just but it connects to your point right yeah i mean i mean again this is all anecdotal for coming from my side uh anyway is that you know but growing up in in silicon valley and i've known a lot of people who cancers and who seem to be dealing with autoimmune things and i know a lot of very ambitious hard driving people it's baked into the culture i grew up yeah and you know and um and sometimes i've just wondered about these naturalistic observations again these are not controlled studies where some of the most um hard-working long-hour athletic academic hybrid founder people are the ones that oftentimes are dealing with severe health issues and you know like how could that be well maybe there's a relationship and the more i learn about the kind of general backdrop of supporting health sleep being fundamental and all the rest and you know natural light exposure but not too much uv and you know this kind of thing you gotta kind of wonder you you i'm not saying people shouldn't work hard i i otherwise i'm headed for a quick death because i've always worked very long hours mostly from a place of enthusiasm sometimes fear um but i guess you know you the immune system is a is a highly uh conditional system yeah i'm not saying mellow laid-back people don't get cancers but has that ever been looked at whether or not temperament and and propensity for autoimmune induced diseases uh correlate i haven't seen it there may be i mean what i have seen and to your point i think there's really strong data that among people who have autoimmune diseases stress results in flares of their autoimmune diseases and so so so if you have it stress lack of sleep all this stuff can can result in flares i haven't seen data on whether it's sort of like at the ideological level of actually causing it but i think that you know this mouse study of these these mice was sort of you know eye-opening for me and i was you know working crazy hours and as you heard i was on a mission i'm still on a mission which is to find drugs for patients like my mom and that you know that meant that i worked crazy crazy hours i teach medical students and um they work crazy hours it's it's really impressive and and striking and at times a little concerning but um so you get this diagnosis thank goodness they figured out it wasn't lymphoma and it was castleman's because that at least gave you a kind of a thin end of the wedge to start exploring various treatments at the time was there any treatment for castleman's disease known treatment at the time there were no approved treatments um but sort of as we were talking about earlier about like sort of information asymmetry um there was a drug that was um uh originally developed in japan uh for castleman's um but my doctors didn't know to try it they gave a form of chemotherapy to me um which fortunately chemo sort of saved my life just in time but there was this drug in japan that like it's pretty strong data that works for castleman's but that just like information hadn't and the drug is available in the u.s for another condition that information exchange just hadn't happened and actually i'll share a quick story about that drug it's called tocilizumab and um it was made by a doctor named kazoo yoshizaki or discovered by a doctor named kazoo yoshizaki and um uh i had heard from a colleague that kazoo had given it to himself before it was given to any other humans to prove that it was safe and um old school medicine right this is the 90s and and monoclonal antibodies were a new technology and so apparently he was afraid to give it to patients because he didn't know what it's going to do so he's like i'll give it to myself so i heard that and i said kazoo i heard you gave your yourself teslizumab he said no no i didn't give it to myself the nurse the nurse gave it to me i was like all right all right kazoo i love the specificity exactly um and so he gave it himself and he didn't die when he got it um but it was safe enough for him so he studied it in castleman's patients it got approval for castleman's in japan and then it got repurposed for rheumatoid arthritis here in the u.s and a number of other autoimmune diseases so it's approved in the u.s for autoimmune diseases but like i said it was made for castleman's in japan approved and available but my doctors didn't even think to try it um chemo saved my life um but then i relapsed a few weeks later we tried that drug from from kazoo from japan it didn't work for me it only works in about a third of patients and so um i ended up needing a combination of seven different chemotherapies adramycin cytotoxin atoposide velcide exalitamide rituxan like the worst chemos out there um was what i ended up needing to get my disease into into remission and just to give you a sense for how sick i was this is now the third time that i almost died in a six-month period i was so sick that once they started giving me that combo of seven chemos i started feeling better with every dose and these are like the worst chemos in the world but because they were killing my immune system which was producing cytokines which was killing me i actually felt better on chemotherapy and and eventually um i got well enough to where i could be discharged from the hospital and there's that picture i showed you from the book which is me a couple weeks after i got out of the hospital um and i was just so thankful to be alive yeah we'll post a link to that photo as well into your book of course um yeah that photo if you show that photo to the typical person they're they're not going to say that's a healthy looking person but you said you were so grateful to be alive because relative to where you were before i mean 100 pounds of fluid it's crazy accumulating in your legs and body prior to that you were in a very unique position because you have this um inquisitive mind it's very clear you were motivated not just from your illness but motivated generally based on the story about your mom um and people would listen to you is my guess they would at least listen to your questions as i'm reading into this a bit but i think many patients don't know what questions to ask they don't know whether the person they're asking has access to the best answers or even the answers um i like to think most doctors are benevolent so let's just assume that but they're also busy and um they get as confused as anybody i'm not trying to knock on medicine here but this is just the reality so simple question when a physician finishes their uh their training all the way through residency and they start practicing let's say an oncologist or a general practitioner in the united states but perhaps elsewhere is the typical physician accessing the literature often i know they're required to do some continuing medical education but it could be the case that their education around a disease is just locked in at the time they finish their residency plus any major updates that come through how does this work because i want to know when my physician finished training and i want to know how often they read papers and i want to know who else is on their uh committee of of of people that they share ideas with i want the most connected physician in the world to be treating me yeah and and i do too and i think that the problem is is that given all the constraints and requirements of a typical physician they just don't really have that much time to do all the things that we want them to be doing so um you're right physicians are reading the literature but typically it's because they have a patient with something that maybe led them to it or maybe um someone sent that paper to them it's it's very random and sort of piecemeal you you know no doctor can can look at millions of papers for example and they can't even look at the hundreds that they maybe would be relevant for the diseases that they treat and so they get sort of some watered down summaries they go to a conference and they hear sort of what's being told but it's very piecemeal and i think the big takeaway from from this whole conversation is that so much of this is piecemeal and it's not systematic and it is random and it's did your doctor happen to come across this one paper um as opposed to the world that we should be in which is where um where it shouldn't matter what doctor you go to see because the data is the data i mean this whole idea of like you know we talk about getting second opinions from doctors it's like for some reason we call it a second opinion yet we believe that what's being told is like exactly what should be done and it's like well it's an opinion right and oftentimes second opinions you know um aren't consistent with the first opinion because their opinions i mean they're educated they're driven in science and driven and um are oftentimes grounded in evidence um but it's still you you just don't know if if your doctor is going to have the information that's needed for you which is sort of scary right like we we sort of we we want to go to our doctor and believe that like we like you know full trust like you know you've got all the answers and actually i'd sort of have this concept that i i talked about in my book which um maybe will resonate with you and what we're talking about now i called it the santa claus theory of civilization which is before i got sick with castleman's and when i was a medical student i had this sort of idea that there were like rooms of scientists and doctors collaborating working together to come up with solutions kind of like santa's you know workshop and the elves are working together and as soon as they as soon as humanly possible that a drug could be discovered it's at your doorstep like as soon as they can figure out but then i've sort of realized that actually like there isn't a you know there aren't workshops there aren't groups of scientists and doctors you know sitting together to figure out solutions and if they are it's just not necessarily at the pace that you would hope that it would be at and so i think that that's just you know one of the the many things that's been a bit depressing yeah i mean i'm going to resist the temptation to editorialize too much on that point uh because i want to get more information from you but i can't resist saying that one of the things i've really wished for for a long time is that the the model of how biomedical research is done in the united states would shift from what we call the independent investigator model where we each have a lab you know huberman lab is not just a podcast it you know was and to some extent still is a laboratory space although i've certainly pared down the size of my lab in recent years for the podcast reasons and other reasons but the point is that in this country you get a phd if you decide to do a postdoc and start a laboratory you have a laboratory that's named after you you get funding to do things that are really associated with your name it's like a small startup that can grow into a medium-sized startup or a large startup but you you stay independent the whole notion of the independent investigator is that it's a very romantic model of science but i think we've reached the point nowadays where the sharing of information and collaboration around a particular goal is far more powerful and i don't have a magic wand and the level of influence i will have over the nih is questionable but what i'm really pushing for is laboratories named after a puzzle or a disease or a challenge yep and people coming together to try and solve those issues because it's not just a matter of naming and branding it has everything to do with how willing people are to share ideas as opposed to feeling like they have to fight for their piece of the pie that's exactly right so this is perhaps a conversation for another time but um you've done a marvelous job of not just trying to educate people about castleman's but your story and we'll continue down that path in a moment of trying to solve a problem that was life or death for you and then taking that knowledge and instead of just saying hey i'm going to help other people with castleman's which you have to really say hey let's let's do this for all of disease all of the medicine and it's so admirable i have to ask are there other physicians doing what you are doing or are you the lone wolf out there i think i'm i'm probably the lone wolf in the in this uh scope of what we're doing it's all fda approved drugs all 4 000 and all 18 000 human diseases so i'm not aware of anyone else who's taking this sort of all versus all systematic like let's find the lowest hanging fruit but there are amazing colleagues of mine who work within hematology who the doctor named luke chen who calls me up when he's got patients on death's doorstep to figure out what can we do what can we try we're brainstorming let's try this or try that and and oftentimes they work and this patient's alive because we tried a combination of five different chemotherapies that weren't made for that that cancer and so there are certainly you know really incredible and there's so many incredible doctors all over all over the country and there are some who are really you know pushing the boundaries of what's possible but i'm not aware of any other effort that's being made that's really at the system level of like i don't care in particular the name of the disease or the name of the drug i just believe that the 4 000 drugs we have today should help all the patients who can benefit from them period like no one should suffer if there's a drug at your cvs that could help you and so the the problem is that's not the world we're in the problem is that we got to we got to create that world um and so that's what we're doing yeah and most scientists are incentivized to find new things and most physicians are not scientists that's right i'm not saying scientists are better but they the two need each other that's right so anyway i i will now pull back on my desire to editorialize about how the system could be better um my hope is that some of this will be implemented going forward but if you would you're sitting here now very very much alive how did this story progress sure so um you know i mentioned i got that chemotherapy got out of the hospital um went back to med school at penn um as a third year med student um how much time did you spent six months in the hospital and then about six months in medical leave just sort of building myself back up um uh amazingly i had this um girlfriend caitlin by my side through it all um caitlin never left my side um was just amazing and um got back to med school so it was now a total of a year because six months of hospital six months um recovering and i was so excited to be back and to really get back on that path that i had before which is that i'm going to go into oncology i'm gonna help patients like my mom and i was on an experimental drug uh it's actually a drug that's very similar to the drug that um that my friend kazoo made and um unfortunately about a year after i got out of the hospital i was back in the hospital again with a relapse and um that relapse is really tough um for a few reasons one i almost died again for the fourth time um and i was in the icu for a month um with all of my organs shutting down but maybe it was even harder than that was that i was on that experimental drug that we had hoped would keep me in remission and it was helping other patients and um my doctor explained to me that we were out of options he said david we've tried everything you know we tried these chemotherapies we tried this one experimental drug um there's nothing more that we can do and um there was a few minute period where my dad my sisters and my girlfriend around me and we were just um just bawling our eyes out you know we're this is the world's expert you know to use the santa claus theory like this is santa claus telling you like there's nothing more and i kept probing him like is there any cell type or signaling pathway or is there something we can target like anything said david there's nothing is there anything an early stage about david there is nothing and um so we just you know we just bawled um and then i had a really sort of moment of a moment of clarity where it was basically i heard what he was saying but then i thought to myself you just gave me seven chemotherapies that were made for lymphoma and my multi-myeloma and they've saved my life now three times they're not it's not long term like i know i keep relapsing but like if these seven chemotherapies are working how do we know there's not an eighth chemotherapy or a ninth drug for something else like you can't tell we haven't tried all 4 000 drugs we've just tried the drugs that maybe we thought to try and so i just locked in right then and i turned to my family and just sort of wiped away my tears and said i'm going to dedicate the rest of my life however long that's going to be it might be a couple days maybe it'll be a couple months but however long i've got to trying to find out is there a drug out there that could help me and other patients with my disease that's made for another condition and um i became just totally locked in on this and part of it too for why it had to be a repurposed drug is that i didn't have a billion dollars in 15 years to make a new drug from scratch i mean i wouldn't even know where to start right but i had examples where my life was saved by drugs that weren't made for me and so i just said well we should do everything we can to find something else and so i started storing blood samples on myself every couple weeks um shortly thereafter started doing some work in the lab i was literally an md who had a master's in public health who knew nothing about the lab um but started working we call that uh dangerous yeah exactly very dangerous and and with a clock ticking right so you've got a lack of skills which the clock's ticking down um very dangerous and so um started doing uh laboratory experiments um did a lot of flow cytometry to characterize immune immune cells that were activated did something called serum proteomics where i measured a thousand proteins in my blood who's letting you do all i mean whose lab space are you using so you're breaking no i wasn't breaking that a colleague was very generous people have done it a very very kind colleague gave me some space in her lab and so um i was doing this work in the lab and also trying to look at other drugs that were being used for um related conditions um to see you know what could work for me and um we were making progress i started a foundation called the castle disease collaborative network we really were pushing things forward and i was optimistic that we would find something and then i relapsed fifth time back in the icu organs shutting down doctor explaining to my family that this is it in fact it was so bad at one point that um i had for some reason over these years i think it was maybe a bit of denial i'd never put together a will but um this time the fifth time my doctor told family you need this you need to put down and so um i like had a printer piece of printer paper that the nurse gave me and i sort of wrote down who i wanted my things to go to and i didn't have much but but um cried hugged my girlfriend we were my she was my fiancee at that time caitlin like just so disappointed that like i hadn't figured something out because what i didn't mention is that from that lab work i thought two drugs might be able to work and we tried both of them we tried cyclosporine we tried ivig and it didn't work and i got worse and i ended up you know back in the hospital and so the two drugs we tried i thought i that was like i got my shot and i missed um and uh i felt so disappointed um and i remember saying goodbye to everyone and um and and starting to sort of have life fade away and i thought that was it and they gave me all the chemo they gave me the highest dose of topos at this horrible chemo that you could imagine and um two days later i started to wake up and uh andrew there's this sense i i call it overtime and it's basically like it's like extra time in a game where like it every second counts and i can't tell you the joy that comes from like getting like when you start to wake up after you've said goodbye to the people you love and you're looking at them and like my sister gene is here and caitlin's here and my dad's there i'm like oh my gosh like when you start getting life back that you thought you've lost and this is now the fifth time i can't put into words what it was like but i remember like as soon as i started waking up i saw them and i was like gina i need you to get the lymph node that's in north carolina to philadelphia caitlin i need you to get my serum samples that are downstairs in little rock arkansas to philly like i got another shot at this like and i remember like starting to wake up i'm being like oh my gosh i'm gonna get another shot and so um about three weeks later i was out of the hospital i was back in philadelphia and um that started about a month-long period where i thought all those samples i did more flow cytometry i did more serum proteomics i did immunohistochemistry on my lymph node and when you put all the data together um what i discovered was that a communication line in your immune system or in all of our immune systems called mTOR um was turned into overdrive and i had a lymph node that i had resected during my last relapse where i actually looked at it and i stained it for mTOR activation and it came back blazingly positive and um so i took the data to my doctor and um you know said what do you think about trying an mTOR inhibitor on me sirolimus had never been used before rapamycin is the other name for this drug had never been used before for castleman's but it's approved for organ transplant rejection and um i sort of had nothing else to try and so my doctor prescribed it to me and um you know rapa at the dose of a transplant dose so i take rapamycin at the same dose that a kidney transplantation patient would take it's a lot higher than the typical longevity dosing that people do my dose of rapa for longevity is zero zero yeah i'm not a fan okay we could talk about that a little later yeah we definitely a lot of people that were taking rapa for off of it for longevity purposes i don't want to because i'll get it wrong like i don't know what peter t is doing right now he's a friend we could call him but my understanding is that a number of people who were very bullish on rapa for longevity are no longer bullish on rapa for longevity yeah i've definitely seen that that shift and i'm not sure if it's based on human data because i don't think anyone's ever done the data the study in humans but but the reason that people were bullish on it is that every organism that you give rapamycin to the earlier you give it to them the longer they live now these are organisms that are in cage settings that are not getting exposed to viruses and pathogens so that's probably part of it i mean i think that whatever maybe longevity benefit you get from the metabolic aspect of rapamycin i think that's counteracted by the fact that we don't live in cages and we actually get exposed to pathogens and so there's probably a negative effect in terms of survival um because rapamycin is a very potent immunosuppressant the doses that i take i take such a high dose that if i were to get your kidney transplanted into me my immune system wouldn't notice your kidney in my body i mean that's that's the the level of dose i take and so um so uh serolimus is approved for organ transplant rejection as you mentioned it's used sometimes in the setting of longevity um and it had never been used before for castleman's in the three and a half years before i started taking it i almost died five times for my disease i said goodbye to my family on five different occasions and my doctors were sure i wasn't going to survive since starting rapamycin it's now been 11 and three quarter years that i've been in remission on this drug and it's just sort of like it feels like such a dream awesome i mean just no other word for it uh your description of overtime yeah is uh i think a very apt one um and i find it uh equally apt that when you're emerging from near death you're calling plays like like a quarterback you're telling your sister what she's gonna do with the lymph node she's gonna run the lymph node downfield right you're calling plays and like to me like you know you're the quarterback playing quarterback again and i can't help but ask you know the past that you had as an athlete uh do you you think it served you i mean the the level of drive and determination to say like oh these eight drugs helping for a while they're no longer helping there's got to be a ninth try the ninth doesn't work okay let's try something else almost dead come out of near death all right you run the lymph node this way i mean it's almost impossible to not wonder whether or not you learned some of that resilience playing sport a lot from playing sports i mean i think that uh your listeners may not know georgia even has a football team but we do have a football team um is that any good uh it depends on who you ask i'm sure it's very good good enough to be in in that's right some league yeah it's division we play ivy league schools so it's like patriot league ivy schools um but the reason i mentioned that is that um we lost a lot of football games um so uh you know certainly there's a bunch of things i learned from football i mean first off i decided when i was eight years old that i want to be division one college quarterback i decided as an eight year old and andrew i literally had poster boards all over my walls with how far i could throw a football how accurate i was how fast my 40-yard dash time was how fast my mile dash for the next 10 years and that's literally that's all i could think about i was just locked in and that sort of like 10 years of like working towards a mission is sort of the same sort of approach you need to take to solve a massive problem in healthcare you know to discover a drug it's that same sort of you know just constant drive so i think one part was that it was the first of what's now been a few of these like sprints that i've gone on so i think that was part of it another is um mentioned sort of loss and resilience you know we lost a lot of football games you get back up and you just sort of keep fighting um but also um physical pain and um and challenges you know broken both my collarbones broken both my hands um at different times i mean i remember there were times when uh for punishment for the team we did something called rolling where like literally like you just start rolling on your side on the football field until everyone like gets sick and then like and then you stop rolling and like but that's like you're rolling for like many like for a long time until everyone gets sick um that's the kind of like physical like i don't know i wouldn't say use the word abuse but it's the sort of physical like demands that get put on your body that enable you to then gain 100 pounds of fluid in the hospital and be in the worst pain you could ever imagine i mean it was way worse pain than breaking my collarbones but like i'd felt bad pain before and so like i can feel some bad pain now and i think that a lot of that came from football i also think that when i was in the icu for that first six month period i learned a lot about myself and i learned a lot about how do you overcome challenging situations and um i think there were three things that really helped me so the first was that the whole time i was in the icu for that six month period i had this clear vision for the future which was a family with caitlin who i was dating at the time and a career discovering drugs for patients in memory of my mom so that like clear vision for the future helped to deal with what was just horrible excruciating pain because of the fluid that you gain around your organs it felt like i was getting basically simultaneously stabbed for for you know months at a time so one is vision for the future two was that i got so much strength from my family around me like my dad my sisters caitlin like they were holding my hands and i could feel their strength in my hands and like i i could they were like literally helping me to keep going and i remember there was a moment um during the when i very first gotten sick so the first time i almost died from my disease and doctors came in said i wasn't going to make it we had no diagnosis at this time said goodbye to my family you know just heartbroken and i remember with every breath i took just just the horrible pain and so when when you have that much pain with every breath you start slowing your breathing and um i was starting to let go i was i was just i was you know letting go and i thought that i was maybe going to miss out in a couple days of life but you know i'm in a lot of pain i'm just going to slow down and let go and i remember hearing my sister gina was on on my left side she was holding my hand i remember her looking at me and everyone else was crying and sort of like i think it was maybe um had had an idea for what was going to happen but gina was holding my hand and she said just breathe dave just breathe and i remember when i heard that i was like all right i'm gonna do one more breath and it's gonna be really painful but i got this and i did one more and i did another one and fortunately the medicines that i'd received helped me to to make it a little bit longer and so the key takeaway for me was that like you can do anything for like one minute or one hour or one day but you can't do like i if you told me at the beginning david you're going to be in the worst pain of your life for six months it's going to be horrible you're going to suffer your organs will be failing no way i would have the strength to survive that but i could survive for one minute and one hour and one day and i think that i think a lot of that you learn i think i learned some of that from playing football and i think that um just this sort of like putting your body um uh through a lot of challenges i think helped me a lot older sister or younger sister two older sisters yeah lees and jean are seven and five years older than me awesome man as the younger brother of a older sister they're the best they're the best they're the best the best yeah big big shout out for the for the sisters older and younger yes the best i'd like to take a quick break and acknowledge one of our sponsors function last year i became a function member after searching for the most comprehensive approach to lab testing function provides over 100 advanced lab tests that give you a key snapshot of your entire bodily health this snapshot offers you with insights on your heart health hormone health immune functioning nutrient levels and much more they've also recently added tests for toxins such as bpa exposure from harmful plastics and tests for pfaces or forever chemicals function not only provides testing of over 100 biomarkers key to your physical and mental health but it also analyzes these results and provides insights from top doctors who are expert in the relevant areas for example in one of my first tests with function i learned that i had elevated levels of mercury in my blood function not only helped me detect that but offered insights into how best to reduce my mercury levels which included limiting my tuna consumption i've been eating a lot of tuna while also making an effort to eat more leafy greens and supplementing with knack and acetyl cysteine both of which can support glutathione production and detoxification and i should say by taking a second function test that approach worked comprehensive blood testing is vitally important there's so many things related to your mental and physical health that can only be detected in a blood test the problem is blood testing has always been very expensive and complicated in contrast i've been super impressed by function's simplicity and at the level of cost it is very affordable as a consequence i decided to join their scientific advisory board and i'm thrilled that they're sponsoring the podcast if you'd like to try function you can go to functionhealth.com slash huberman function currently has a wait list of over 250 000 people but they're offering early access to huberman podcast listeners again that's functionhealth.com to get early access to function you had an amazing team so another parallel to to football and um and another signal that for people um combating disease or just general health issues that that social support piece is so key i mean i mean there's so much data on this and i mean we've done podcasts about this and we could probably do a hundred more and the message is always the same which is to the best that you can surround yourself with at least one person you can rely on and be the best way to do that is to be that person to people yeah you know um should you stay healthy you have that person should you not be healthy you have that person so um yeah and over and over it's really um an incredible story because you emerge from it with 11 years of overtime do you still think about that as overtime fifth overtime yeah do you although i will admit i think to your question i don't have the same sort of because there's this in overtime there's a there's both fear and clarity and and the the fear i think drives some clarity i think you'd be able to talk to the science of a lot more than i would um i will say as 11 years and three three quarters of a year go by um there isn't maybe the same heightened sense of like i'm in overtime but you know every once in a while i have a port where i get my infusion every few months on my chest i've got scars on my neck from where lymph nodes got taken out and every once in a while i just sort of put my hand here and here and it reminds me okay like i'm in overtime like i got to be really thankful um because you know we we don't know how much time we have the brand's wild in this way we had a guest on this podcast michael easter he wrote the book the comfort crisis it's an incredible book really about how to navigate life generally and and doing really hard things um voluntarily and uh and he go do really hard expeditions and then come back from them with a renewed sense of gratitude for like the smallest things the smallest things and i asked him you know how long does that gratitude last and i think he said about two months oh you know and then it resets and of course those weren't life or death circumstances of the sort that you're describing so he just goes on more of these things right great um and it's a wonderful book and an important dare i say an important book for people healthy uh and certainly healthy or sick i think this this notion that you're on borrowed time or overtime it's hard to hold on to because you also have to just live your life but clearly you're making the most of that and and as i mentioned earlier you know in service to others so your background as a as an athlete helped you navigate this health challenge then the health challenge dovetails with your work as a physician and you're really a physician scientist because you you hold both titles and uh formally and um and as a practitioner so nowadays do you get contacted by people all the time whose kid or themselves are dealing with it with a challenging disease with the question is there a drug that's approved that can help me or combination of drugs we do we get contacted a lot and um to share sort of what the these last 11 and a half years have looked like so um i after medical school i actually um enrolled in business school in part because i um realized that the greatest barriers to progress did not appear to be scientific or medical they had to do with things like getting people to collaborate with one another efficient use of resources coming up with a strategy to solve a disease so it was actually in business school that i discovered serolimus to save my life and after business school i joined the faculty at penn and set up a lab and um we got started out first focus on castleman's and you know first it was better understanding how does mTOR play a role in castleman's he started treating other patients with the drug that i'm on serolimus and so i'll never forget um we treated a patient in brazil and then treated patient in new zealand and then but i just heard about them i wasn't physically with them but then the fourth patient we treated was a patient named joey who was a child um he was a 13 year old boy at children's hospital philadelphia and um it completely turned his disease around he was he was literally dying in the children's hospital we used serolimus and i would come in every day to see him and i'll never forget um you know seeing the blood work seeing him the couple days after we started serolimus and it was just andrew it was so incredible to like see this boy who was on death's doorstep start to turn around because of the drug that saved me and now we're saving other people and again we'd use it in brazil use in new zealand but i hadn't seen them i hadn't like felt like what his family was feeling i actually just saw joey a couple days ago and his parents a couple days ago as well um he's a he's a college student at temple university now but so that for me was this huge moment it's like oh my gosh like the drug i'm on is helping other people it's not just this sort of one-off thing and then we found a drug that's used for bone uh for a bone marrow condition called myelofibrosis um that we thought could also treat castleman's patients so there's a young girl named kyla in a hospital in chicago wasn't responding to anything and she didn't respond to my drug either serolimus and we recommended her doctor um try uh ruxolitum first time ever for castleman disease and she responded incredibly well she's in college now marquette university she's going to be a nurse and um that was amazing i was like okay not only did we find this drug for me and give other people but now we find another drug for castleman's like wow maybe there's even more we can do so our lab kept working and working and that's when michael the patient with angiosarcoma came to us back in 2016 and we found out that this drug for melanoma could actually treat his angiosarcoma cancer and then it's oh my gosh we can find for another disease and this over the course of uh of the last 11 years has totaled 14 drugs for diseases they weren't intended for and with every one of them we get so excited and then we also think to ourselves how many more drugs are there out there that are made for one disease that could actually treat more diseases and so that meant that three years ago um as artificial intelligence was really continuing to move forward at an incredible pace my co-founders grant mitchell and traces of core grant was utilizing artificial intelligence to support drug companies with finding new uses for their medicines to find subpopulations that might benefit from their medicines but we thought what if instead of using ai one drug company at a time to find you know one new use for medicine what if we could utilize artificial intelligence to scan across all drugs and all diseases to find the best opportunities so we started every cure three years ago and since starting every cure um you're absolutely right we get contacted by lots of patients and families and we try to help them any way that we can and i'll share a couple really exciting examples and at the same time that we're having all these incomings about people that are on death's door what we keep focusing on is can we find these matches like lidocaine for breast cancer or dfmo for bachman buff that syndrome i mentioned can we find these matches and do the work so that way people don't get to death's doorstep do the work to do the clinical studies get the word out so doctors are prescribing them so they're not coming to us for a hail mary but we're actually getting the work done ahead of time so that way the drug is just being used can we match every drug to every disease that they can treat and do the work to get it to people um because that's really the i think the way that we really solve problems at scale as opposed to this sort of that one-off hail mary approach but i'll share a couple um one-off approaches that i'm really really proud of one of them is a patient um named al in vancouver who wasn't responding to any medicines he also has castleman's and the subtype that i have the really deadly one and um the number one ranking uh number one ranked drug in our machine learning algorithm for castleman disease when we ran it for the first time two years ago um was uh a tnf inhibitor actually mentioned tnf earlier and based on some other work in our lab we thought that maybe we could try it for him um he received the drug he responded really well castleman for castleman tumor necrosis factor yeah tnf inhibitor yeah so sorry not tnf directly the inhibitor of tnf exactly so we give him adalimumab and he responded incredibly well he's been doing great now for two years published in the new england journal of medicine earlier this year can i ask you forgive me for interrupting sure okay so so an inhibitor of tumor necrosis factor alpha tnf alpha is involved in inflammatory response earlier you said that this inhibitor can help treat this condition of multiple strokes yes in childhood okay strokes are basically bleeding out in in brain areas essentially right okay i'm sure there's a mechanistic pathway that can be you know uh connected connected to that right um involving any number of things uh and i'm sure there's a mechanistic pathway that can be linked to this other observation does it matter to you like does it matter that uh like i i think i actually have seen papers where you know tnf alpha is involved in the kind of like endothelial neural interface and then you have inflammation and then you have some shearing and then you're bleeding and okay so like i can it's a just so story in my mind um that works right um does it matter or is the goal to screen drugs in patients um as these hail mary passes and figure out things that work and then worry about mechanism later i mean this is typically not the way science and medicine is done especially in this country people don't like the notion of eating a plant or eating a seed and then seeing benefits and not knowing what the molecules are i mean we like reductionist science in this country this is changing somewhat but that's been the pattern to you for a patient that's suffering is all that matters that they get better i could understand why that might be the case yes 100 all ever since i saw my mom die from brain cancer all i've wanted to do is think about how can we help people with these horrible conditions and then when i went through my own experience i realized that oh my gosh helping people with these horrible conditions may not be spending my whole career to develop one drug it might actually be spending my whole career finding out all the uses for all these other drugs and to use a football analogy it's like we've got all these drugs that are on like you know the one yard line um that could be useful for a new condition but there's no incentive to do that so can we just push them in so yes it's all about can we help patients and i think it goes bi-directionally so when a drug helps a patient like like that tnf inhibitor helped help help al we believe it's because uh t cells in castles patients cd4 positive t cells are producing too much tnf when they become activated and we've shown that in the lab so you can actually start working backwards so like when a tnf inhibitor helps a patient so let's look at their blood and let's figure out why and then maybe i can learn something for the we can learn something for the next patient so i think it should be bi-directional clinical observations and in the lab and let's go in both both directions and then i also want to share about another patient named joseph who um has a rare cancer called poem syndrome and so his uh girlfriend tara reached out to us in one of these sort of hail mary attempts um because his doctors were getting ready to take him off life support because he was dying from his poem syndrome and um we recommended three drugs that are typically used for multiple myeloma we mentioned myeloma earlier myeloma and poems are really really similar so again it wasn't rocket science to recommend three drugs that are used for a really similar form of cancer for um for his condition um but he was dying his doctors were afraid to try chemotherapy they were worried that that it would kill him the drugs himself but they were gonna take him off life support so they tried it and he responded incredibly well he's been doing great it's been over a year and a half of remission and i mentioned all these examples because like each one of them sort of teaches us something else about this and that's that like they're similar conditions yet they weren't being you know but we weren't thinking creatively yes there were no treatments for poem syndrome but there were treatments for myeloma and so you know and there's shared mechanisms between the two so i think that um some doctors are doing this but we have to create a system where we uncover these and then we can get it out to the masses so they use them the fear is that you try one of these novel drug applications drugs aren't sorry existing drug used in a novel way yeah be very specific with the language here and a patient gets sick or dies yep you know it wasn't but gosh maybe a decade and a half ago that this kid was given gene therapy and died yes and that delayed setback however you want to view it uh the whole field of gene therapy by a very long time all it takes is one patient death yep i mean even and then in the supplement realm i don't know if you remember this but like um because we're about 10 years apart you're younger than i am um is uh tryptophan the amino acid to induce sleep because you know it's in the serotonin synthesis pathway and um but the binders used in a particular batch of tryptophan that i think was sold out of japan although um ended up being contaminated and somebody got very ill and died you couldn't buy tryptophan for a long time now tryptophan not as critical as life-saving drugs in my opinion except the naturally occurring yeah of course but all it takes is one bad situation and the whole thing gets vaulted for a very long time so how do you mitigate that risk is it by only focusing on patients that are really it you know kind of at the end of their rope in terms of possibilities and it seems to me that the medical community has been pretty um open to what you're doing uh but i have a little bit of a like a kind of like traditionalist fear voice in the back of my head like like what if you start giving aspirin to kids with this other condition and kids start getting really really sick and you can't pull those symptoms back because it's one thing to halt a drug symptoms stop it's another to to halt a drug and and those side effects symptoms whatever you want to call them persist and god forbid a kid dies yeah you know so what you're doing is is extremely exciting but um it's also risky yeah you're asking all the right questions i mean i think that there's a couple ways that we think about this and one is that we really do try to avoid the hail marys as you mentioned and as you as you thought lots of people are reaching out to us and unless we have solid evidence about a drug for that disease we are we don't want to just speculate because to your point speculation can actually lead to harm so and if there's a you know fine line between you know speculation that could save a life and harm and of course we are only doing what we're doing to help people um it's a non-profit organization we literally just exist just to help people there's nothing else here to it so um we definitely don't want to cause harm um so one part is that we focus on you know we look across everything versus everything every drug versus every disease to find the best opportunities and then we move them forward in a really rigorous way we do laboratory studies we do clinical trials we evaluate the results of those trials we look in observational data so we can be really rigorous about the things that we do at the end of the day say we are advocating for this use that's one way to do it the other thing to consider is that there's always a physician that's prescribing the medicine to the patient and so the best thing we can do is to educate those physicians and those patients on what it is that maybe we found in a clinical trial or in the lab works but it's still got to be decision between the patient and and their physician and what about outside the domain of disease in the domain of health very brief anecdote uh colleagues of mine some don't like when i tell this story but i'm gonna tell it anyway love it because um many years ago i went to visit columbia university school of medicine right so like columbia meds fantastic place and there's a nobel prize winning neuroscientist there met with him to discuss his work he happens to be an md he's a researcher and um i noticed he chewed six pieces of nicorette inside of the 45 minutes we met so i asked him like what are you doing guy was in his late 60s then now he's in his late 70s very very sharp nobel prize wasn't an accident he looked at me like this and he said nicotine is protective against alzheimer's and parkinson's he said smoking and there wasn't really vaping then but smoking will kill you but nicotine isn't carcinogenic nicotine despite raising blood pressure um protects dopaminergic neurons and cholinergic neurons so that's why i do it and he said that he used to smoke and he was much sharper now he uses nicorette and i thought should i use nicorette so i said should i be doing this he said you're young you probably want to wait until you're in your 60s or 70s he said but it's protective against parkinson's and alzheimer's and he also said don't get your head hit don't play football you know this kind of thing okay so i took that and um i decided all right someday i'll chew nicorette now nicotine is all the rage i actually don't suggest that most people take nicotine because of the blood pressure effects yeah he's a constrictor there could be other things it's very very popular but very very habit forming slash addictive so i want to be very clear about that but i realized there are really smart people inside of my profession who have medical degrees who are doing things to promote their health like take lithium not continuously but for one or two months per year i know a colleague doing that colleague like taking nicotine is now in his late 70s and still very very sharp now you can't run the the other you can't be the control experiment for yourself but what i want to know is do you think that there are things that are of value that people can and should explore to maintain or promote their health to avoid disease in the same kind of framework that you're approaching the treatment of disease absolutely and i think we need to be as rigorous in this realm as in you know in the in the world of treating disease i think that the challenge is that there's such limited data right like you said you know you your one friend is doing really well but it's hard to know was it because of the nick red or is it you know that he was going to be fine um either way i just think we got to figure out ways and i think you've done such a great job of spotlighting these opportunities so that way people will think about it more and actually will do further investigation um you know i was thinking in terms of this um prevention side of things of course about glp1s and so of course there's interesting evidence emerging and you'll know better than i will um but around uh improvement in parkinson's symptoms in patients that are on glp1s and have parkinson's disease improvements or reduction in risk of alzheimer's and also breast cancer people who are on glp1s and so there's likely a very complex interplay between weight loss and maybe it's the glp1s are reducing risk of these things because of metabolic effects maybe there's direct effects maybe it's anti-inflammatory so these are you know preventative concepts um with pharmaceutical products that um that i think we we need to be thinking about and to your point you know there really isn't an actual line between natural and pharmaceutical i mean think about the drug i'm on sirolimus it's called rapamycin because it was found on the island of rapinui in the soil of i don't know if you know that story it was found in so rapamycin or serolimus the other name for it was found in the soil of the island of rapinui and there was a researcher at wyeth pharmaceuticals who was going all around the pacific ocean to a bunch of different islands and picking up soil samples and he thought that you know maybe i could find some drugs in the soil and he eventually found this molecule now called rapamycin where they synthesized a bunch of of it it's completely naturally occurring from from and the other name for rapinui is easter island it's from the island you know from easter island so synthesized it and they initially thought that it might be a good drug for um as an antifungal but it's a lousy antifungal and so they're trying to figure out like what else could it do and they found out that it's a really potent immunosuppressant and um and in fact the research into the immunosuppressor role ended up you know really accelerating understanding of how the mTOR pathway works in the first place and it actually is an amazing story um that was it was done on on radiolab about how um it eventually um or at one point it was shelved wyeth and pfizer decided not to study it and then it sort of got taken off the shelf and it got approved for organ transplant rejection but i just think about something like that i mean if that scientist hadn't picked up the soil sample in rapinui i'm not sitting here with you talking to you right um and of course there's thousands of people all over the world who aren't sitting here talking to anyone because you know that drug wouldn't have been discovered and and it was in the soil and it's not some you know pharmaceutical synthetic thing you know this is a totally naturally occurring compound so i think our our the line that we put between creatine and you know sirolimus and glp1s there's a lot of overlap here and yes some of these molecules are very much synthesized and you think about the chemos that i've gotten are like horrible compounds that like you probably don't want to put in your body but it's a lot grayer than i think we like to think it is i think the term is bioprospecting uh when people from pharmaceutical companies go out and look for things in nature and then develop drugs from them we had a guy on here very impressive guy chris mccurdy who's down in florida he studies kratom and kratom leaf products kratom is a is a it's being sold as a kind of natural opioid replacement i just should anytime it comes up i have to be very careful because you all cut clips and you take them out of context i'm going to just i've learned how to guard that against that forgive me but kratom products and the kratom leaf have been used by some former prescription opioid addicts to get off those prescription drugs however it's very clear that a lot of these products which are sold over the counter in convenience stores um corner stores 7-eleven etc cvs can also be highly addictive alone and they're sold to kids it's a serious serious issue but the kratom leaf kratom i think is the way it's the traditional um uh pronunciation uh contains a bunch of different plant alkaloids and the synthesized purified kratom is the one that has this pain pain relief aspect that's also can be very addictive um and we discussed the coca plant and cocaine but also other elements within the coca plant that his he runs a laboratory that are being isolated and being tested for different pain relief and psychoactive properties that can be very beneficial to people so bioprospecting is something that drug companies don't really discuss a lot but the way they're doing this is going into nature looking at the crap the kratom leaf the uh coca plant um micuna purines is this velvety bean that um is 99 l-dopa oh really wow yeah which you can buy this over the counter so we think so the line between supplementation and prescription drug is very very fine it's just that there's no control over the the over-the-counter stuff and so this is where it runs into problems and gets a bad reputation and understandably so we don't want people harming themselves with this i'm beginning to think that what's really needed and people in the current administration do listen um to the podcast i don't know if they what they do with the information but um i think we need more thoughtful safe bioprospecting to develop drugs that they can be tested in pre-clinical models animals pre-clinical means animals folks um and then eventually clinical trials but i don't know that we have the time for clinical trials on all these bioprospective molecules or even the molecules that you're talking about which are already fda approved it sounds like a lot of it just has to be run in real time in people like the experiment in some sense has to be done in humans i just don't see otherwise it's going to be you know another 50 years before we have a cure for alzheimer's or or we solve some of the most serious like psychiatric illnesses i i agree it the answer comes from actually testing these things in humans there are so many things that cure mice and they don't ever translate to humans and and vice versa so um i think that i'm really bullish on the idea of leveraging the world's biomedical knowledge and using artificial intelligence to help to prioritize among all these different things and so at the end of the day you know we talk about the 4 000 drugs the 18 000 diseases the reason we do the scoring on everything versus everything is so that we can just know where to start because you know i mean we rank everything versus everything and and maybe the fifth highest scoring thing is is the thing to go after maybe the 10 000th highest scoring thing is the point being is that ai can at least help us to to focus in on where do you start because to your point there's so many opportunities of the existing drugs we have of the molecules that are already available in nature but you need you need somewhere to start and i think ai is really well positioned to direct us humans to where to start amen to that um because in theory with ai you could um develop i guess they call it in silico you could say uh let's run a 10 000 cell cultures in parallel the graduate student cost is nothing they don't need to sleep it's ai after all and um with all the properties of of you know this immune cell type different concentrations of drug and while it's not a real world experiment you can get an indication of what the outcome might be and what might be worth taking a better look at is that is that what you're imagining that's right and also um that that's a true simulation where the work hasn't been done what also is the case is that as you know there are labs all over the world running experiments all the time on various uh cell lines and animal models and in humans all of that's happening and so what i really am bullish on using ai for is not to simulate something that hasn't been done yet but it's actually to find connections between what has been done so um we know you know the example earlier that one lab found increased pdl1 expression in this one form of cancer and this drug inhibits pd1 so therefore let's make a connection that no one had made yet so there are two truths that hadn't been connected you know a you know and b are connected b and c are connected let's connect a to c and i think that ai is particularly well suited um to to find these patterns of things that we know so so it's not a total it's not a simulation it's actually just connecting um really like breadcrumbs into into one story you're a parent i am uh how do you navigate health care for a kid knowing what you know about medicine and knowing what you know about what medicine doesn't know i'm a very rigorous parent of two kids when it comes to health care yeah i've got a seven-year-old and a three-year-old which um it feels like a dream to be here talking to you 15 years after i went through um all that i've gone through definitely feels like a dream that i'm able to tell you i've got a seven-year-old and a three-year-old i'm just i'm so lucky but like you said um i'm really rigorous you know uh you know one of my doctors suggests you know try this for for my daughter um i you know ask a lot of questions i mean i try to really stay on top of things and it um sort of gets me thinking about something i was hoping to ask you about and uh it's that over the course of my challenges and sort of ups and downs that i've had in my health um and and the work that i've done to find treatments i've found that i think there's this circuit that again i'd love to get your thoughts on so i find that it starts with hope so i'm hoping for some future so maybe it's that my child's health condition will be improved or my health condition but you know you start with some sort of hope that you hope something will happen and then that drives some amount of action so like maybe in my case you know i run experiments on my own blood samples and then that results in some impact that um you know maybe i get learn something maybe that drug is going to work for me and that impact gives me more hope and then it creates this this circuit so it's hope action impact which gives you more hope action impact and i haven't figured out exactly like if there's some some some neuroscience behind this but i found that for me and just thinking about you know your question around whether that's you know helping your child with the medical issue that they're facing or again my own that that circuit has just been a game changer for me i don't know if there's if there's some neuroscience behind that that you can help me to understand this this hope action impact uh there absolutely is and uh the person who deserves credit for um revealing this circuit is my colleague joe parvizzi at stanford who's a neurosurgeon wow who was in the brain of awake patients uh stimulating different brain areas uh in anticipation of a neurosurgery like you described earlier and had electrodes in a structure called the uh mid-cingulate cortex um it's part of a larger network of course as is every brain structure uh and he noticed when he stimulated a sub-region called the anterior mid-cingulate cortex that patients would report in real time that they felt like there was some challenge kind of bearing down on them like going into a storm each one described it differently but that the stimulation also made them feel as if they wanted to lean into that challenge now here's where it gets really interesting if he marches the electrode back a millimeter or less completely different set of effects laterally completely different set of effects so the anterior mid-cingulate cortex seems to be the seat of some sort of sense of tenacity to lean into challenge wow it gets really interesting when you start looking at the data of kind of volumetric imaging of this structure in people that for instance successfully overcome obesity through exercise and diet or people who decide to undertake some other challenge like a cognitive challenge or learning how to dance something that's challenging yeah and then you look at the literature on longevity and you look at this group of so-called super agers which is a misnomer because they actually age very slowly right yeah uh and what you find is that psychologically they report a very strong will to live and their anterior mid-cingulate cortex is the one of just several areas that seems to maintain volume as they age relative to these age match cohorts now none of these are perfect experiments on their own but when you start to put these together as a collection of things you realize that all the things that are the reverse of depression so what's major depression a lack of positive anticipation of the future um uh lack of understanding or belief rather lack of belief that uh changing one's behavior could change circumstances like get a job or new relationship or overcome something and you see the exact inverse of that in people with a kind of naturally large or perhaps um self-fertilized uh anterior mid-cingulate cortex these people report a lot of positive anticipation about some hopeful future event wow and it's not always a big monumental thing sometimes these are you know closer milestones sometimes it's a bigger thing and they live longer and they have this incredible will to live so it seems that you know taking this to its kind of extreme conclusion that the will to live sits somewhere in the network of this structure it's not just this structure and it's intimately related to dopamine uh networks so reward reinforcement and learning networks and all the rest yeah um but you know it's hard to pinpoint one structure but if i had to you know put a pin in one structure would be joe parvizzi's discovery of the anterior mid-cingulate cortex and it has all the elements of you described hope yeah plan yep and action exactly repeat yes and so for people who are not ill or who are ill having that um sequence a good friend who is in uh tier one special operations uh in the seal teams he described this as um when there's a challenge you have to shorten the horizon get a forward center of mass but think duration path and outcome what path how long outcome iterate and it's the same way you work down a football field is the way you work you you know kind of lay through these challenges so um again i'm i'm creating a tapestry from a bunch of disparate things here but but none of is it is outside the realm of a peer-reviewed science it all sits there um so we haven't scanned your brain i don't think we need to to know that your anterior mid-cingulate cortex is clearly um very robust and i would wager the hypothesis that it was probably um built and reinforced through your postering up of athletic goals on the wall of your childhood bedroom i think you're right i think you're right yeah the the more you work you know the better your times get the better those numbers get and then you know as you said it it becomes a true circuit you know the thing you're hoping for when you get closer to that thing you're hoping for it drives you to take more action and then and then you can you can keep going in that circuit well clearly you are living in that circuit and it lives in you could you tell us about ways that people can get involved with every cure i have to imagine more information is better than less sure what can people do sure so um anyone can go to everycare.org ideas and tell us about maybe there's a drug that you were prescribed off label by your doctor or maybe you're a researcher and you think that a drug could be used in a new way so you can go to everycare.org ideas tell us about that medicine and we'll look into it we'll compare it next to our ai predictions and we'll determine whether maybe it can be moved forward um if you're an expert say in neuroscience or you name the the area you can go to everycare.org experts and you can sign up so that if we find a drug that might be useful for a condition that you're an expert in you might be able to give us advice and guidance on you know maybe what the right development path is and anyone who's watching can help us to raise awareness about the work that we're doing so you can follow us on social media at everycare.org and beyond i did a ted talk recently you can help spread the word and check that out and finally of course people can support our work financially we're a non-profit organization clinical trials are expensive you can go online everycare.org/donate and donate to our work and we're just so excited for this opportunity we have to help people with the drugs that we have but we realize that it we can't do it alone we actually really need the whole community to get behind us where is funding currently derived from is it just public support so right now um about half of our funding actually comes from the u.s government from an agency called arpa h they're one of our earliest supporters and the other half comes from individuals who decided that this is important um it may be that they have a loved one that has a condition that they would love for us to work on or maybe it's that they just want to see um you know us be able to help patients with with the drugs that we already have and um we are just so excited of that opportunity to match the drugs we have to the patients who need them fantastic and i should ask um if a drug application is discovered is there a feedback mechanism for you guys to derive income from it or this is a completely non-profit it's completely non-profit so i think by the end of you know let's say the next few years i will guess that nearly all of the opportunities that we advance forward are the same dose the same formula no one makes any money off of them whatsoever i think there'll be rare cases where let's say the drug looks like it'll be effective but it needs to get into the brain where a tweak will have to be made where a different dose or formulation will be needed i think they'll probably be rare cases where probably a company will be need it to be spun out to do it but for the vast majority we're non-profit we just want to take the drugs we already have to use them for the disease that could benefit from them terrific we'll put a link to it in the show that'd be awesome david thank you so much for coming here today to share your story with us and just a ton of actionable knowledge for people that are healthy continue to explore options safely yeah think about what's possible understand there are things that are known there are a lot of unknowns and again explore safely for people that are ill find a disease-related group that really has um an eye on what's new what's existing who the best people are search for a few of those is kind of what i took away from that and um thank you for doing the work you do it's amazing we need more people like you uh you're truly one of a kind so we're immensely grateful uh that you've taken hardship and transmuted it into so much good and love to have you back sometime to talk about all the millions of other things we didn't have time to talk about but this has been incredibly enriching for me and i'm certain it has for everyone else well thanks so much for having me thanks for all that you do to advance the public health and also to get the word out about the work we're doing through every cure thank you for joining me for today's discussion with dr david fagenbaum to learn more about his laboratory's work and his non-profit every cure please see the show note captions if you're learning from and or enjoying this podcast please subscribe to our youtube channel that's a terrific zero cost way to support us in addition please follow the podcast by clicking the follow button on both spotify and apple and on both spotify and apple you can leave us up to a five-star review and you can now leave us comments at both spotify and apple please also check out the sponsors mentioned at the beginning and throughout today's episode that's the best way to support this podcast if you have questions for me or comments about the podcast or guests or topics that you'd like me to consider for the huberman lab podcast please put those in the comments section on youtube i do read all the comments for those of you that haven't heard i have a new book coming out it's my very first book 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 and that's based on more than 30 years of research and experience and it covers protocols for everything from sleep to exercise to stress control protocols related to focus and motivation and of course i provide the scientific substantiation for the protocols that are included the book is now available by presale at protocolsbook.com there you can find links to various vendors you can pick the one that you like best again the book is called protocols an operating manual for the human body and if you're not already following me on social media i am huberman lab on all social media platforms so that's instagram x threads facebook and linkedin and on all those platforms i discuss science and science related tools some of which overlaps with the content of the huberman lab podcast but much of which is distinct from the information on the huberman lab podcast again it's huberman lab on all social media platforms and if you haven't already subscribed to our neural network newsletter the neural network newsletter is a zero cost monthly newsletter that includes podcast summaries as well as what we call protocols in the form of one to three page pdfs that cover everything from how to optimize your sleep how to optimize dopamine deliberate cold exposure we have a foundational fitness protocol that covers cardiovascular training and resistance training all of that is available completely zero cost you simply go to hubermanlab.com go to the menu tab in the top right corner scroll down to newsletter and enter your email and i should emphasize that we do not share your email with anybody thank you once again for joining me for today's discussion with dr david fagenbaum and last but certainly not least thank you for your interest in science