Skip to content
The Joe Rogan ExperienceThe Joe Rogan Experience

Joe Rogan Experience #2372 - Garry Nolan

Garry Nolan, PhD, is an immunologist and professor at Stanford University School of Medicine. He is also a business executive and Executive Director of the Board of the Sol Foundation, a research and advocacy center focused on UAP studies. https://www.thesolfoundation.org Hunt with confidence using onX Hunt. Start your free trial today at: https://huntsmarter.smart.link/srwbpznr2 This video is sponsored by BetterHelp. Visit https://BetterHelp.com/JRE

Garry NolanguestJoe Roganhost
Aug 28, 20252h 37mWatch on YouTube ↗

EVERY SPOKEN WORD

  1. 0:001:17

    Nolan’s Stanford work: cancer immunology, instrumentation, and data-driven biology

    1. GN

      (drumbeats) Joe Rogan podcast. Check it out. The Joe Rogan Experience. Train by day, Joe Rogan podcast by night. All day. (instrumental music)

    2. JR

      Gary, very nice to meet you, sir.

    3. GN

      Nice to meet you as well.

    4. JR

      Thank you for doing this. I really appreciate it. Um, tell everybody what you do. Tell everybody what your official position is. You- you're a professor at the School of Medicine at Stanford. What- what do you do?

    5. GN

      So, my day job is in cancer research and cancer biology, mostly immunology and cancer. Much of what my laboratory does is not so much the biology of cancer, but developing instruments that create the data that allow us to analyze the complexities of how the immune system interfaces with tumors, and how tumors basically re-enable, uh, the immune system to help the cancer itself. So the problem's been we don't have the ability to collect enough data, or not until recently, to collect and understand what all of that means, so we've been kind of poking in the dark for decades. And so probably for the last 20 years, I've developed a number of instruments and turned them into companies that allow everybody to access a level of information they couldn't get before.

  2. 1:176:35

    How tumors evade and manipulate the immune system (MHC, immune checkpoints, progression)

    1. JR

      So, uh, ex- ex- explain that. The- the immune system allows the tumors? Ex- wh- wh- wh- wh-

    2. GN

      So what happens is that there's sort of a, there's a dance between the mutations that initiate a tumor and then, uh, sort of an evolution of how the tumor eventually learns how to trick the immune system to not recognize it. So we have all kinds-

    3. JR

      Hmm.

    4. GN

      ... of inter- I mean, literally every day, uh, every person, you'll develop five cancer-like objects inside of your body, but the immune system, uh, and your body has a way of shutting it down very quickly. But with enough time and with enough variation, tumors will eventually evolve in a way that trick the immune system, not only to- to not recognize them, but in fact, to help them and feed them in a way, to create an inflammatory environment that actually then the tumor uses to propagate its own cell division and then metastasize.

    5. JR

      So it's a normal function of natural human biology to create tumors?

    6. GN

      It's not so much a normal function. It's a byproduct of what evolution is, that when the genes mutate when a cell divides, or if you go out and, you know, stand in the- in the sun, uh, too much for instance, you get skin cancers because you're getting ionizing radiation that's changing the DNA, making a mutation, and some of those random mutations will initiate a cancer. So for instance, I have, um, a mutation called MIDF E318K. It's, uh, a mutation that I was born with. It didn't- it wasn't in my family, and it causes both melanoma and kidney cancer, which I've had both. I've had a dozen, uh, melanomas alone. Um, you know, we didn't find that out until a couple of years ago, but I've been following it over the years and we basically figured out, okay, it's gonna have to be this. So we had my sequ- my genome sequenced. But there's... That's just one of hundreds of different kinds of mutations that can occur that are on a path towards creating a cancer. But the cancer can't survive if the immune system recognizes it. So eventually what happens is there's this detente that is reached between the immune system and the cancer, where the immune system basically ignores the cancer. So Jim Allison here in Houston, uh, won the Nobel Prize back in 2018, uh, for understanding one of these turn-off signals about the immune system u- that the cancers use to turn off the immune system, and that by showing he could block it, his wife, Pam Sharma, ran a bunch of clinical trials at MD Anderson that showed in fact that this could actually turn a 5% survival disease in melanoma to a 50% survival. And that then created the whole immunotherapy field that the world is, uh, taking advantage of today.

    7. JR

      Wow. So- so what is- what is cancer actually doing? Like how- how did it- uh, how do tumors develop this ability to trick the immune system? Is this so- something that other animals have?

    8. GN

      Oh, yeah. Oh, yeah.

    9. JR

      So it's a constant-

    10. GN

      It's a constant battle.

    11. JR

      ... battle.

    12. GN

      So- so- so for instance, there i- there are proteins on your cell surface. I won't get too immunologically deep about it. Uh, they're called, uh, major histocompatibility complex proteins. So for instance, if I were to try to just randomly do a- a tissue transplant from me to you, it's very likely that it would be rejected, and it's because of those MHC proteins that it's rejected. What's happening is that your cells are presenting your internal cell biology to the immune system, and it's saying, "Okay, you're- you're a friend, not a foe." So when cancer usually initiates, there are disruptions that happen and proteins are made incorrectly, et cetera. And so what these MHC proteins are doing in some cases is they're presenting the internal damage to the body and the body's saying, "Oh, there's something wrong with this cell. We better wipe it out. We kill it." These same proteins are what the immune system uses, for instance, to go after viruses. So when you get a virus infection inside of the cell, the body has a way of chopping those proteins up inside of the cell, presenting it via MHC, and then the immune system attacks it. So what, one of the first things that actually tumors do is they learn to turn off the MHC proteins inside of themselves.

    13. JR

      Hmm.

    14. GN

      So the ability to show that I'm damaged is shut down. And so the immune system doesn't go on full alert for that. But then there are other mutations like divide when you're not supposed to. Uh, you know, avoid this kind of induced cell death called apoptosis, uh, and not others. And so it... Cancer doesn't just, like, start and then the next day you've got it. It's a progression of events. You have these precancerous lesions. You have, like, a benign tumor, which eventually becomes a metastatic tumor.Um, and, uh, and so the... But the immune system is key at every stage of the development because if you can reactivate the immune system in just the right way, then you can prevent the cancer from basically, uh, spreading or from metastasizing, or from killing you, essentially.

  3. 6:358:21

    Transplants, systemic immunosuppression, and the dream of local immune control

    1. JR

      Is there a potential for... Uh, w- given the understanding of this, is there a potential for using this for organ transplant patients-

    2. GN

      Oh, yeah.

    3. JR

      ... where it locally would stop recognizing this as a foreign-

    4. GN

      Uh, that's exactly what-

    5. JR

      ... organ?

    6. GN

      That's exactly what is done. In fact, you, um, when you get a tissue transplant or an organ transplant, you're suppressing the immune system. The problem with that suppression is that you then put yourself at risk-

    7. JR

      Right.

    8. GN

      ... of cancer. Because what you're doing is you're turning off the immune system's ability to r- to combat and go after a cancer the moment it forms. So most people who are under immune suppression are at risk both of, let's say, virus infections, bacterial infections, but also for their cancers.

    9. JR

      So would the, the potential be to turn that off locally? So you could turn that off to this- on the specific organ?

    10. GN

      Th- th- th- that would be a great thing to do if we could. Right now, the only things that we have are systemic.

    11. JR

      Right.

    12. GN

      So, yeah, I mean, uh, for instance, if you could deliver to the organ that you're transplanting anti immuno sup- you know, basically immunosuppressives locally, that would be great. We don't have that yet. But that would be via a form of gene therapy.

    13. JR

      But the problem with that be that if you... Like, let's say, you had a r- a lung transplant.

    14. GN

      Right.

    15. JR

      If you had a lung infection-

    16. GN

      Yes.

    17. JR

      ... it would be catastrophic.

    18. GN

      Do you wanna come work in my lab?

    19. JR

      (laughs)

    20. GN

      You're, uh, y- yeah, you're, you're accepted as a graduate student in the Stanford Department of, uh, Pathology.

    21. JR

      Well, that was easy.

    22. GN

      Yeah.

    23. JR

      (laughs) We got... I have a few friends that have had-

    24. GN

      Mm-hmm.

    25. JR

      ... organ transplants.

    26. GN

      Yeah.

    27. JR

      Which is w- and it's, you know, it's very disturbing knowing that they're so vulnerable to any kind of infection because of these medications that they have to take in order for their body to accept the transplant.

  4. 8:2115:07

    High-dimensional immune profiling and personalized medicine (50–60 markers, pseudotime)

    1. GN

      One of the problems is that there are literally hundreds of different types of immune cells and, you know, really until recently and frankly until, um, a technology my lab developed about over a dozen years ago, we couldn't look at all of the immune cell types all at once in a single picture. Um, so I came from a laboratory, Len and Lee Herzenberg, uh, when I was a grad student at Stanford, and they had developed an instrument called the fluorescence-activated cell sorter. And that allowed you to look at three proteins at a time and if you could know ahead of time what the cell types were that expressed the proteins that you're interested in, you could look at just those three cell types. Then I came up with a way to look at, you know, 50 or 60 proteins at a time, sort of stepping up what they had already taught me how to do, uh, and then suddenly that gave us the ability to look at nearly every cell type, uh, in the, in the body, uh, and immune cell types, and then that gave us the, let's say, the raw data to build math- mathematical models that we could do better predictions of what outcomes would be.

    2. JR

      And how is that... Uh, like, uh, how are you... What are you applying, what... In, in terms of, like, real world scenarios, how are you applying this?

    3. GN

      Well, so for instance, um, there's a kind of leukemia called AML, acute myelogenous leukemia. It starts in the bone marrow, uh, and it is a distorted, uh, version of a myeloid cell type. It starts as a s- as a stem cell and that stem cell goes down a number of different paths, and depending upon the person, the disease is sufficiently different that it might follow a slightly different path towards what becomes the disease itself. And so being able to trace the path and to know which steps along the way that it takes to become what becomes then the metastatic, uh, lyph- uh, leukemia, um, uh, could only be accomplished by having enough markers that allowed us to trace everybody along the path. It's kinda like if I wanted to follow you from w- who you are as an egg through development through to who you are today and I had snapshots every month, I need different markers to measure what you are as an egg versus what you are as a baby versus what you are as an adult. And so each of those different markers in my world would be different proteins that tell me something about an adult leukemia versus a baby leukemia. And then we use something called pseudotime, which is a mathematical concept that allows us to stitch together those photographs. I could take a random box of photos of you from an egg to who you are today and I could just, by hand, put together the most likely path and sequence of what you were from the earliest to the latest.

    4. JR

      Mm-hmm.

    5. GN

      But we needed the data and we needed the means and the instruments to collect that information so that then the math could come to play.

    6. JR

      That's such a fascinating thing about human beings, is the biological variability, is that everybody is so... uh, we're so the same-

    7. GN

      Mm-hmm.

    8. JR

      ... two lungs, a heart, uh, but so different in how our body reacts to things and what, what happens to us and environmental factors, diet-

    9. GN

      Right.

    10. JR

      ... stress, all, all sorts of different factors, and you're kinda piecing together this puzzle-

    11. GN

      Right.

    12. JR

      ... of all these things.

    13. GN

      And, but what you're doing is you're, you still have to pay homage to the fact that those differences exist. And so while, you know, the... my cancer might be the same class of, let's say, melanoma as another person's, uh, the complexity of what allowed that cancer to become are so different that the drugs that would work for me might not work for another person.

    14. JR

      Mm.

    15. GN

      And so that's what re- basically requires us to personalize the medications in a way that, uh-... gives the right des-, uh, drug to the right person. So, I, I've started probably half a dozen companies and sold them, uh, at places like Roche, et cetera. Actually, my most recent company we sold to 10x Genomics, which enabled us, enables them now, uh, because of a patent I created back in 2011, to scale up the amount of information that we can collect at a time. That then, when layered on t- top of what, for instance, 10x Genomics already did, which is doing what's called single-cell genomic, uh, analysis, we could scale that up a hundredfold to get a hundredfold amount the information. But the problem with that is that I can collect all that data and make, uh, an analysis of a cancer for you, but it might be a little bit different than another person. So, what we have to do then is develop techniques that allow us to narrow in on what the differences might be, so that when I develop a drug for person X, it works for person X and not for person Y. Right?

    16. JR

      Mm-hmm.

    17. GN

      The right way. So, there's a lot of personalization in medicine that is required. Um, the, the diversity that makes humanity great and that makes humanity able to survive in the face of so many challenges is that there are individual differences that one person might survive and another won't. Um, it's the same thing with cancers and it's the same thing with drugs. I mean, the, you know, for instance, with certain drugs, it, it ... One of the first things I learned in pharmacology when I was, you know, way back in the day, is that there's always a benefit, uh, to damage ratio that you're having to deal with, that a drug has a positive outcome, but there are side effects. And so as scientists or as clinicians, we make a choice based on the statistics, who will benefit the most and will it benefit the most, but by the way, there's all these side effects that might affect you. Uh, and, um, you know, overall, globally, 60% of people will survive. But since I don't know anything more about your specific disease, I am, by law, required to give you the 60% drug-

    18. JR

      Mm-hmm.

    19. GN

      ... until I know or can distinguish that your disease is a different subclass than the 60%. And that's, in fact, a lot of what, um, pharmaceutical companies are doing, is they're trying to marry a diagnostic to the disease itself, the disease subtype itself, so that if you can show that 90% of the people, uh, of this kind of subclass will survive, you have to, by law, choose that diagnostic to make sure that the person doesn't have the subclass before you give them the 60% drug.

    20. JR

      Mm-hmm.

    21. GN

      Does that make sense?

  5. 15:0722:43

    Genes, sun exposure, and future gene editing: Nolan’s melanoma/kidney cancer story

    1. JR

      Yes. Yeah, it does. Um, the narrative has always been, uh, over the, you know, last few decades, stay out of the sun.

    2. GN

      Mm-hmm.

    3. JR

      But recently, people have started saying, "No, it's actually you need to become accustomed to the sun." And the real issue is people using sunscreen all the time and then going out and getting burned. Obviously, your situation is very different-

    4. GN

      Yeah.

    5. JR

      ... 'cause you, you have a, a specific gene.

    6. GN

      And I'm Irish. (laughs)

    7. JR

      Yeah. (laughs)

    8. GN

      So ... (laughs)

    9. JR

      Well, that's, that's the problem, right?

    10. GN

      Yeah.

    11. JR

      The genes of the people that lived in cloudy-ass places-

    12. GN

      Right. Exactly.

    13. JR

      ... for hundreds of thousands of years.

    14. GN

      And my mother, when we were kids ... I mean, I'm 64 years old, so when I was a kid, you know, we'd go to the beach in Connecticut and they'd smother me in, in, you know, uh, um, coconut oil.

    15. JR

      Oh, yeah.

    16. GN

      Right?

    17. JR

      Yeah, baby oil-

    18. GN

      Yeah.

    19. JR

      When I was a kid-

    20. GN

      Yeah. Yeah.

    21. JR

      ... everybody had baby oil and everybody got barbecued.

    22. GN

      Yeah. Plus I worked in the, you know, in the fields as a kid for, you know, farm, farm labor.

    23. JR

      And that's not good.

    24. GN

      That wasn't good for people.

    25. JR

      The burning, the, that's the real, the damage to the skin-

    26. GN

      Right.

    27. JR

      ... and then it manifests itself as cancer far later in life.

    28. GN

      Right, right.

    29. JR

      Yeah.

    30. GN

      There's all these subtle, let's call them, uh, smoldering mutations that are waiting for a second or a third hit-

  6. 22:4326:40

    Early detection, imaging tradeoffs, and CT scan radiation risk

    1. GN

      He was great. Yeah, he was great. But, um, you know, I- there are ... Um, so for instance, if you can catch most of these cancers early, then that's what's important. So I think probably one of the most important, let's say, changes to our medical system that could be initiated would be, frankly, the use of things like MRI, not CT scans, 'cause CT scans are known to cause cancer. (laughs)

    2. JR

      Which is so crazy.

    3. GN

      Yeah.

    4. JR

      Like, when did we figure that out?

    5. GN

      Uh, I mean, they- there was, like, a big study just published recently-

    6. JR

      Yes.

    7. GN

      ... that said, "Here's what happens to people once CT scans were implemented," and you see this sudden spike in the-

    8. JR

      Ugh.

    9. GN

      I mean, it- it- again, it's this cost-benefit ratio. If you didn't have it, certain people wouldn't have- you know, wouldn't know that they have a giant tumor in there.

    10. JR

      Right.

    11. GN

      I mean, so for instance, I had, um ... When I had kidney cancer, I was actually at a restaurant with friends doing a business deal actually. And I went to the bathroom, and it was blood. And I said, "Okay, we gotta go to the- you know, we gotta go to the, you know, to the emergency room, like, now." And then they did a CT scan, and they see this- the brachial tree around my kidney was just a big diffuse mess, and they came in and said, "You've got- you've got cancer." And-

    12. JR

      Did you have to have your kidney removed?

    13. GN

      Yeah. Yeah. Yeah.

    14. JR

      (laughs)

    15. GN

      It was, um-

    16. JR

      Oof.

    17. GN

      But, you know, it- it's okay. I'm alive.

    18. JR

      It's nice to have two of 'em.

    19. GN

      Yes, exactly. Um, I'm alive. But, uh, y- you know, it is- it's this early detection is important. And I was lucky that it hadn't metastasized yet. Um, it's called r- it was, uh, called, uh, clear cell renal cell carcinoma. Um, but, you know, so ...... surveying the body, and these companies that are out there right now which do it, I think they're really important, because even if you are young and you have no suspicion you're gonna have cancer, having that baseline against which you can compare later changes is important. Because I could do, for instance, a CT scan or an MRI of you, and I'd find lots of little anomalies. And they're generally in the field called phantomas. They are these objects that, mm, may be worrisome but we won't know that they're worrisome, and certainly not if you do a biopsy of them and, you know, poke a needle into your chest to pe- pe- pick at a piece of it. Um, but if I come back six months and it's changed, then maybe it's something we need to go after, you know, more seriously. So getting those kinds of regular scans, I think, is probably one of the more, um, important things that can be done, but not by a CT scan.

    20. JR

      Which is crazy 'cause we've b- we're doing them for so long.

    21. GN

      Yeah.

    22. JR

      Did they ... They still do CT scans, though-

    23. GN

      That's-

    24. JR

      ... because it's necessary.

    25. GN

      It's necessary-

    26. JR

      It's the only way-

    27. GN

      ... for certain things.

    28. JR

      Right. Which is letting people know this might cause cancer is just like, yikes.

    29. GN

      Yeah. But maybe, for instance, there'd be a way, um, to treat someone with a drug ahead of time that would minimize the effect of the CT scan.

    30. JR

      Ah.

  7. 26:4030:57

    Cancer as ‘broken contracts’: evolutionary cooperation, devolution, and why no universal cure exists

    1. GN

      Well, it's interesting because what's, what's happening with X-rays or CT scans is a fast-forward of the kind of random damage that causes cancer in the first place.

    2. JR

      Mm-hmm.

    3. GN

      And so because it's random ... Um, let, let me kind of go back a little bit as to w- w- why does cancer happen in the first place. So let's go way back in evolution to the first time that, that there were single cells versus the first time that two cells met each other and said it was better to, uh, to join forces and cooperate rather than to divide at each other's expense. So in the process of that happening, those two cells came together, or three or four cells. They basically said, "Together we're better than alone." But there were actually social compacts and contracts that, at the genetic level, were being formed between all of these cells. And so as things got more and more complex, uh, more and more complex contracts were formed, to the point at which what could happen is that any one of the breaking of a complex contract could actually then initiate a cascade that becomes cancer.

    4. JR

      Mm-hmm.

    5. GN

      So rather than we thinking of, um, cancer as being a forward progression in evolution, it's actually ... Another way to think about it is that it's a devolution back to the core fire of the desire to divide.

    6. JR

      Mm.

    7. GN

      And so by breaking the contract, by bak- by breaking the controls on the system, y- cancer is allowed to blossom. So the problem is that every tissue type, whether your lung or brain or whatever, has a whole different ecosystem of contracts that have been formed, and so there's no one-size-fits-all drug that will kill off all cancers, because the contracts are different.

    8. JR

      Mm.

    9. GN

      It's not like you can bring in a lawyer and fix, you know, agricultural contracts versus-

    10. JR

      Entertainment.

    11. GN

      ... maritime or whatever.

    12. JR

      Yeah.

    13. GN

      So that's the ... You know, you have to a- have a flexible enough mindset, 'cause if you get stuck in this "It's a forward evolution" as opposed to that, "It's a breaking of contracts," you might miss out on an opportunity for, uh, how to develop a dre- a, a, um, a therapy or a drug that would help people.

    14. JR

      One of the things, um, that I, I wanted to ask you on, I don't even know if you know anything about this, but is there a connection between IVF and the amount of ... 'Cause y- you have to-

    15. GN

      Mm-hmm.

    16. JR

      ... take some pretty extreme hormones.

    17. GN

      Mm-hmm.

    18. JR

      There's a lot of stuff that women have to take. Is there a connection between that and hormonal-related, uh, tumors?

    19. GN

      I honestly don't know, so I don't want to opine-

    20. JR

      Okay.

    21. GN

      ... and then have, have my colleagues send me emails tomorrow scolding me.

    22. JR

      Okay, good. Uh, well, I'm glad you answered that way. I, uh, y- ... I was told by someone who I really trust that there is, and then we tried to Google it and it said there's not, but that's not surprising.

    23. GN

      Probably there hasn't been the right kind of study yet, and if there is not, there should be. I mean, certainly any hormonal imbalance is not a good thing. I mean, you imbalance-

    24. JR

      Right.

    25. GN

      ... the metabolism of the system and you can ... I mean, so for instance, back to my specific disease, uh, the MIDF, I f- uh, there's all kinds of things like inoc- n- n- n-acetyl- n-acetylcysteine-

    26. JR

      Mm.

    27. GN

      ... betaine, all these other drugs that are out there for longevity.

    28. JR

      Mm-hmm.

    29. GN

      Well, if I look into the metabolism of what my cancer is, every single one of those is a, is a disaster for me.

    30. JR

      It accelerates.

  8. 30:5736:23

    Diet, metabolism, and the philosophy of science (being ‘righter tomorrow’)

    1. JR

      Hopefully, yeah. Um, because of your specific type of cancer and your situation, like, do you have to, like, very closely monitor your diet?

    2. GN

      Um, I probably shouldn't eat as much meat as I do.

    3. JR

      Meat?

    4. GN

      Uh, yeah, um-

    5. JR

      Why meat?

    6. GN

      Well, because, you know, fats, and a lot of them... The fats, uh, dissolve, uh, a fair number of toxins. Um, you know, it's, it's not necessarily a good thing. I mean, that's been relatively well-shown that too much meat, as opposed to... I'm not advocating vegetarianism. I think there's a-

    7. JR

      Mm-hmm.

    8. GN

      ... there's a happy medium. I mean, we grew up in an environment where we had both. I mean, we're omnivores.

    9. JR

      Mm-hmm.

    10. GN

      Uh, and we succeeded, I think, because we're omnivores, uh, as a society, as a, you know, as a civilization. So, um, but, you know, charred meat, for instance-

    11. JR

      That's the issue, though, isn't it?

    12. GN

      Yeah.

    13. JR

      Isn't it? Burnt-

    14. GN

      Yeah.

    15. JR

      Yeah.

    16. GN

      I mean, it's carcinogens. I mean-

    17. JR

      Yeah.

    18. GN

      ... you know, you're making all kinds of... It's a, uh, uh, it's a witch's brew of nastiness, uh, that tastes good. But, you know, the reason why it tastes good is because th- the humans who survived learned to use fire to kill off the bacteria in rotten meat.

    19. JR

      Mm-hmm.

    20. GN

      And so the flavor of that probably was engineered into our evolution. Uh, but again, it's a cost-benefit.

    21. JR

      But didn't th- the cooking of it also allow us to absorb more protein?

    22. GN

      Um, I'm not sure about that.

    23. JR

      I believe so.

    24. GN

      Okay, that could be.

    25. JR

      I believe that's the case, that, that cooking meat actually allows it to be more easily absorbed by the body.

    26. GN

      Could be broken down more readily.

    27. JR

      Yeah.

    28. GN

      But, but certainly it kills bacteria. So, you know, d- day-old or three-day-old deer-

    29. JR

      Right.

    30. GN

      ... you know, that you just killed-

  9. 36:2344:06

    AI transforms biomedicine: agentic ‘immunologist-in-a-box’ and tumor–immune insights

    1. JR

      I think it's really important to illuminate to the general public the sheer scope of the task of trying to figure out what is going on in all these different...... things that can go wrong and right in the human body.

    2. GN

      Yeah.

    3. JR

      And that it requires this fucking insane amount of work-

    4. GN

      Yep, yep.

    5. JR

      ... by many, many, many people.

    6. GN

      And, uh, you know, and then the amount of data that had to be collected now. And so here's the difference, is that, you know, there's data, there's evidence, there's conclusions, and proof, and that's, uh, an uphill climb. But proof, the next one up is meaning. W- my lab has been largely responsible, at least partly responsible, for the data deluge that's out there in the world, both in how to do tissue biopsy analysis, how to do single cell analysis, et cetera. And, you know, data felt good for a while. It was like this, you know, this feedback loop of, "Oh, wow, I can get all this data." And then suddenly, you look at it and you go, "Well, what the fuck does it mean?"

    7. JR

      Mm-hmm.

    8. GN

      And so humanity has this habit of backing itself into a corner, and then f- suddenly f- finding this eureka moment that gets it out. And so our eureka moment about two years ago was artificial intelligence, where suddenly I had the ability ... So normally, I would cut through all this data and go, "Okay, well, it seems myeloid suppressor cells are important here and T regulatory cells are present here." Okay, I get on the phone or send an email to whoever the local expert is, either on Stanford campus or around the world, and try to get some information from them. But then now you're dealing with hundreds of cell types, each individually of which, of which have thousands of variations themselves, and each subtle variation means something. Uh, and there's no expert for any of that, but AI can be at least in part that expert. So suddenly, I have 22 million papers published, you know, in the wh- in all the fields of science, uh, you know, uh, several tens of millions just in, you know, or s- several millions just in immunology alone. An AI can be the sleuth for me, can be both the an- angel and the devil on my shoulder, that can make sense of things in ways that I never would have been able to before, especially with agentic AI, which ... So we, for instance, in my lab, have developed, uh, an agentic AI that is basically an immune, uh, an immunologist scientist in a box. We can give it the raw data, and we can pose a question in natural language. Uh, and then we say, "Hey, make sense of this and turn it into a network." Normally, that would have taken a graduate student, along with a couple of post-docs, months and months and months to put it all together. Now, in three hours, we can get pictures and hypotheses of how all that data fits together in ways that I never could have done before. You know, at the beginning it hyp- ... In the beginning, it did a lot of hallucinations, which you probably heard about in AI.

    9. JR

      Mm-hmm.

    10. GN

      But my answer to my colleagues is, "Some of my best students hallucinate." (laughs)

    11. JR

      (laughs)

    12. GN

      Right?

    13. JR

      Right.

    14. GN

      And, and so ... But, you know, the human's still in the loop. And so with all of this together, now we can make meaning out of the data, and we can skip a lot of the intermediary steps and speed it up, and it's just getting better. I mean, we, for instance, have put in a couple of papers now where ... So for instance, in, uh, where my special- one of my recent specialties is what's called the tumor-immune interface. So you have the tumor, you have the immune system, which is coalescing on, you know, near ... And then in some cases, the tumor creates a boundary, uh, a barrier between itself and the immune system, uh, where there might be certain kinds of cells that the immune system, uh, the tumor has told the immune system, "Ignore us, we're not here." Um, and then ... But what we now can do is, there's ... Well, on the, on the other side of when you look at, let's say, complex patient populations, you find these things called tertiary lymphoid structures. So your body has 220 or so lymph nodes, okay? And the lymph nodes are where the immune system makes decisions, let's say. Uh, it turns out that in the middle of tumors, the body has evolved a mechanism to create what essentially looks like a lymphoid structure in the middle of the tumor. It's sort of a forward camp of immune cells, that the more of those you see in a tumor, the better will be your outcome as a patient.

    15. JR

      Mm-hmm.

    16. GN

      And so we used, uh, a cohort of, uh, colorectal cell, uh, basically colon cancer patients, where we looked at hundreds of biopsies, and we did that pseudotime analysis, where we looked for mature tertiary lymphoid structures, and then we looked for immature, slightly less mature, even more less mature, et cetera. And we were able to backtrack to the cell types which need to come together that would then form the more mature. What use is that? It's a nice paper, but it also now tells us h- what we might do to create more of these in a tumor.

    17. JR

      Mm-hmm.

    18. GN

      Because the more... We already know from multiple kinds of tumor types now, that the more of these tertiary lymphoid structures you have, the better off will be your outcome with chemotherapy. So it might be, for instance, that once we know that you have a disease like this, we could give you some kind of therapy, a virus or what have you, that goes and homes to the tumor, seeds the beginnings of these initiators with ... There's these cytokines that are produced that are necessary for initiating the formation of these objects. Uh, and so th- there's a huge benefit to that, but we never would have found those, in my lab at least, uh, without the AI, 'cause it-

    19. JR

      Wow.

    20. GN

      ... it basically did the work for us.

    21. JR

      That's fascinating.

    22. GN

      Yeah.

    23. JR

      Now, are you using like a standard l- large language model or are you ... Do you have like a, a, a specific structure that's built that interfaces with large language?

    24. GN

      C- correct. So we use, um ... Well, we can use pretty much any of the LLMs, but right now we find that OpenAI is the best.... for us at least. And then we create an agentic overlay, uh, basically a what's called, you probably know, chain of thought.

    25. JR

      Mm-hmm.

    26. GN

      Which is a series of questions. So how we taught it was we basically came up w- here's a, here's a hundred kinds of questions a scientist would ask about the immune system. And then we tell ChatGPT, "Now create a thousand questions like this." So, you know, it's artificial, uh, data, or artificial questions. We curate those to make sure that they're good. Then we do a hundred hypotheses, and we create thousands of types of hypotheses, et cetera. And the same for tests, uh, that you might run. So now, from A to Z, we have, uh, an agentic AI that you give it raw data, it knows what to do with the data, it then generates hypotheses for you, and then it literally tells you the kinds of experiments you should do next to prove or disprove the hypothesis from the raw data.

    27. JR

      It's a genius in the lab with you.

    28. GN

      Exactly.

    29. JR

      Is, is OpenAI learning from this agentic AI?

    30. GN

      Oh, yeah.

  10. 44:0656:42

    Commercialization vs academia: Stanford culture, retroviral tools, and translating research

    1. GN

      And we first thought to turn it into a company, 'cause that's kind of one of the things we do in my lab is if ... 'Cause I've always thought that it's important to give back to the taxpayer the money that they've invested in us. Uh, and the best way to do that is commercialization, and totally un- uh, you know, unapologetic about that, even though that got me in a lot of trouble at Stanford in the early days, uh, when, you know, making money was, you know, it's c- commercialization was evil, um, uh, even at Stanford. And so, uh, I think that that's an important process, because s- s- scientists are good at asking maybe the questions and coming up with solutions. But scientists aren't the best at commercializing it and turning it into a product that can be used or testing it, you know, in large, um, communities. So the AI that we developed, we thought, "Okay, well, maybe we can do this." We thought, "You know what? AI is moving so fast, why don't we just give this to the community? Why don't we open source this?" We can use it for maybe specific targeted purposes, but we're basically gonna publish the whole thing on GitHub, uh, to let other people use it, 'cause we've seen other people make claims about stuff that they've already made, and it's like, "Mm, ours is better." So why don't we just put it on GitHub and let people learn from it?

    2. JR

      The commercial, the resistance to the commercialization, what was the initial argument?

    3. GN

      So, uh, th- back when I was a grad student in the, in the, uh, '80s, um, basic research, as opposed to translational research, um, was considered the height of intellectual desire, right? Basic research and, and we're not here to make money. We're here to discover things. And that's important, and nearly every major discovery and every major therapy in the world came from basic research. But then, you know, there were limits to how much money you could give to basic research, and then there was a desire at a certain point to say, "Hey, well, that's ... What ... Are you gonna do anything about this?"

    4. JR

      Mm.

    5. GN

      "You know, are you gonna make any ... " So translational research became, uh, a push. So this guy, uh, at Stanford by the name of Paul Berg, uh, who won the Nobel Prize for, uh, gene the- for, um, recombinant DNA way back in the day, uh, and, uh, Paul came up with this concept bed to, you know, bench to bedside, meaning that we don't have to be either or. We can be part of an arc, uh, and Stanford wanted to be, uh, and enable within the medical school both the basic research, which we were great at, as well as bringing it directly to the patients as well, so to link clinicians and the desires of clinicians with the basic researchers. I mean, most scientists would be happy just to study anything. You know, just point me at something, and I'll be happy if I can get interested in it. So, uh, and we're no more happy than when somebody recognizes the value of what we do.

    6. JR

      Right.

    7. GN

      But basic research was sort of the height, and there was a push against anybody trying to commercialize. So when I started as an assistant professor ... So I started as a grad student. I went to MIT to work with this guy David Baltimore, um, who won the Nobel for, um, reverse transcriptase, and then I wanted to come straight back to Stanford because I already felt that it was a positive environment for commercialization. My bosses, my former bosses, mentors, Len and Lee Hersberg, had two of the biggest patents at Stanford. They had the fluorescence-activated cell sorter and then what are called humanized antibodies, which brought in hundreds and hundreds of millions of dollars to Stanford. Um, and they actually, they gave, personally, most of their own money away. They didn't ... They made, kept enough to survive, but then they gave most of the money away, and they ran their own lab o- off of a lot of that money. But, so I had learned from them about how to still do basic research but commercialize on the side, and so I wanted to bring that back. But the department that I came into, the Department of Pharmacology at the time, um, I was warned by many professors, uh, "Don't commercialize that." And I ignored them, and I went and started a company that went public on NASDAQ, and many of those same professors came back to me, you know, years later and sitting in my office asking me how to start a company.

    8. JR

      (laughs) Why did you ... Uh, was it just a courageous decision to ignore them? What did you ... Was it instinctual?

    9. GN

      It just was instinct- it was like, because I couldn't see the NIH funding what I wanted to do.

    10. JR

      Mm-hmm.

    11. GN

      So I had developed a way, this will sound scary, but I had developed a way to use retroviruses and make libraries of retroviruses to reverse the process of evolution in a way that rather than viruses hurting the cell, I set it up so that viruses would help the cell.

    12. JR

      Mm-hmm.Oh.

    13. GN

      And once they help the cell, I would figure out what they did. And so we sold hundreds of millions of dollars of targets that way using retroviral libraries, uh, to, um, basically find targets and use v- use th- use some of the benefits of viruses, but to our advantage.

    14. JR

      Just the concept of reversing evolution is fascinating, because it comes with, uh, there's so many ethical implications, but if you didn't have any of those-

    15. GN

      Yeah.

    16. JR

      ... and you could do that large scale.

    17. GN

      Well, I had developed, in David's lab, along with this guy Warren Parr, um, a means, it's called the 293T retroviral producer system. It was a way to make large numbers of these viruses very quickly. It really followed on the work of this guy, Richard Mulligan, um, who'd also been a postdoc with, with David Baltimore, who developed, uh, what was called the 3T3 based retroviral production system and he developed it in Paul Berg's lab (laughs) at Stanford. Um, so there's a lot of sort of, uh, you know, um, interbreeding here. Uh, but the problem with that was it took three months. So I had brought with me a cell line called 293T that I introduced to the lab and said, "Hey, maybe we could use this to make viruses quickly." I won't go into the details of why, but we could do it in three days rather than three months. Uh, and so that now, I mean, tens of thousands of labs use that worldwide and it probably generates the most money for me, uh, every year over any of my other inventions. Just because S- Stanford, rather than patenting it, licenses it.

    18. JR

      Mm-hmm.

    19. GN

      And licenses are forever, whereas patents have a 17-year lifespan. So Stanford made a good choice there.

    20. JR

      So do you think it was just a bias, uh, academic bias? Like we shouldn't be focusing on money, we should be focusing on the work?

    21. GN

      Yes.

    22. JR

      And they missed the forest for the trees?

    23. GN

      Right. But then people, I mean, they eventually learned, you know?

    24. JR

      Right.

    25. GN

      I mean, and it's, it, I, I wouldn't say that it's the, it's the way that people think anymore, um, but it, there's still a little bit of a b- I mean, you shouldn't walk into the lab thinking, "I'm here to make money."

    26. JR

      That's what they're worried about.

    27. GN

      Yeah.

    28. JR

      Right?

    29. GN

      Right.

    30. JR

      That's, they're worried about the bastardization of it all.

  11. 56:421:11:35

    Big-picture AI futures: post-scarcity hopes, job displacement fears, and human–AI integration

    1. GN

      Well, look at Neuralink as a, an example and Elon Musk's stuff, you know, the woman now who can think her thoughts and make stuff happen-

    2. JR

      Mm-hmm.

    3. GN

      ... um, because she's otherwise paralyzed.

    4. JR

      Right.

    5. GN

      Right? I think it was Neuralink that, uh, just showed some of these results. So fast forward, I mean, we're already in an exponential increase in what it is that we're gonna be able to accomplish, and AI will help us accomplish f- get some of these things faster. I can see a time where, you know, I could maybe apply something, I don't necessarily want a surgical implant, but maybe some sort of net over my head that allows me to think through these problems, and I, the AI becomes a, an adjunct to my thought processes, not only what it is that I think, but maybe even provides information back to me, back into my system-

    6. JR

      Mm-hmm.

    7. GN

      ... directly without having to go through the years, so that I can much more quickly come to conclusions. Now, there's all kinds of apocalyptic scenarios you could imagine with that-

    8. JR

      Of course.

    9. GN

      ... as well, but I'm an optimist at heart, uh, perhaps again naively so.

    10. JR

      Me too. (laughs)

    11. GN

      But I prefer that kind of an outcome 'cause if y- if you're not an optimist, then there'll be no progress 'cause all you'll do is worry about disaster.

    12. JR

      Yes. That's a good point. But also realistically, we might be giving birth to a new life form.

    13. GN

      Yes.

    14. JR

      Mm-hmm.

    15. GN

      A- and I think we are.

    16. JR

      A, a superior one.

    17. GN

      And, uh, you know, I welcome the day of our AI overlords-

    18. JR

      (laughs)

    19. GN

      ... running the government rather than hopefully in an unbiased way.

    20. JR

      I've said that too, and people get horrified because they're like, "Well, people are gonna be programming AI."

    21. GN

      D- do you read-

    22. JR

      Like, uh, up to a point.

    23. GN

      A- a- are you a sci-fi fan?

    24. JR

      Yes.

    25. GN

      Do you know, um, uh, the work of Iain Banks, the Culture series?

    26. JR

      No.

    27. GN

      Or Neal Asher, uh, the Polity universe as he calls it? They're like, uh, so basically both of them postulate a future where AI more or less benignly rules humanity.

    28. JR

      When did they write this stuff?

    29. GN

      Oh, probably 10, 15 years ago.

    30. JR

      Man.

  12. 1:11:351:14:38

    Pivot to UAPs: ‘future humans’ logic and why probes/avatars might resemble locals

    1. JR

      Yeah, I think that's ultimately the evolution of human beings. And, um, uh, look, I know you've done a lot of work with UAPs and the like, and, uh, I think you've done some really fantastic work. And you're very objective in your analysis of what this whole situation is. When I look at artificial intelligence, and I look at this, this thing that's clearly taking place right now, and I see what, what human beings are like in comparison to what they used to be like-

    2. GN

      Mm-hmm.

    3. JR

      ... and especially when you look at, like, ancient hominids, the, uh, the alien archetype, this thing that everybody sees-

    4. GN

      Mm-hmm.

    5. JR

      ... supposedly, or one of the many different ones-

    6. GN

      Right.

    7. JR

      ... that kind of looks like what we seem to be going in the direction of being.

    8. GN

      Right. Yeah, I mean, I-

    9. JR

      Which is one of the reasons why I find it so odd.

    10. GN

      So, if you just, for a moment, take UAP and aliens out, or ET or, or interdimensionals, or whatever it is you wanna call them, out of the, uh, question, and fast-forward what humanity's going to do-

    11. JR

      Right.

    12. GN

      ... in 1,000 years, um, and our ability to expand into the local-... galaxy. Um, w- we're not gonna go as ourselves, we're gonna go as, a- a- AI-conjoined entities. Like-

    13. JR

      An avatar.

    14. GN

      ... uh, a- and yeah. And so, when you go somewhere, let's say we don't have warp drive, you're not gonna send yourself. You're gonna send an AI intermediary who's gonna s- establish humanity or whatever it is that we think humanity will be in a thousand or five thousand years, in that local environment. And so, I think the extent to whatever it is that UAP are here today, is somebody else's civilization's version of just this.

    15. JR

      Mm.

    16. GN

      And that y- you wouldn't ... L- the principle, us, behind whatever this is that we might be allegedly, et cetera, dealing with, isn't the thing that's gonna show up, you know. So to the extent that Neil deGrasse Tyson is right about anything, the person who gets on the ship, uh, uh, at the beginning or whatever it is that sends it off is not the same thing that gets off on the other side. But you're gonna send missionaries or intermediaries or probes or whatever, and that if you're gonna interact with the locals, you're gonna make something that looks more or less like the locals, rather than something that whatever it was that you were a million years ago.

    17. JR

      Mm.

    18. GN

      Does that make sense?

    19. JR

      Right. I get what you're saying. So you, you make something that looks like the locals so that they're more likely to accept that it's a real thing?

    20. GN

      That it's a real thing. But not ...you're not, you're not gonna make something that looks like a human because then you'd mistake it as a human.

    21. JR

      Right.

    22. GN

      But you might make something that looks more or less enough like a human, but enough like an alien that you're gonna recognize it as an alien. And again, I'm just speculating. So-

    23. JR

      Right.

    24. GN

      ... so the Daily Mail, don't say, um, you know-

    25. JR

      (laughs)

    26. GN

      ... put a article out tomorrow-

    27. JR

      Oh, they're gonna do it anyway.

    28. GN

      ... ah, they're gonna do it anyway. Some of the stuff that I'm seeing qu- uh, supposedly-

    29. JR

      (coughs)

    30. GN

      ... having quoted as saying is ridiculous. But it's, it's-

  13. 1:14:381:30:14

    How Nolan got involved: Atacama ‘alien mummy’ investigation and Havana Syndrome link

    1. JR

      They get everybody. Mm-hmm. How did you even get involved in this? Let's bring it to that. Like, so you're ... what was your initial introduction to this? Did you have any interest in the idea of UAPs or UFOs?

    2. GN

      I mean, I had a general in- ... so once YouTube started becoming a thing and, you know, you're clicking around and I said, "Oh, UFOs, that's kind of cool." Um, I'm, you know, I read nothing but sci-fi.

    3. JR

      Right.

    4. GN

      I mean, I'm, you know, pathetically narrow-

    5. JR

      (laughs)

    6. GN

      ... in that sense. Um, and so I followed, you know, I, I followed the usual kinds of things that you would see on the early days of YouTube. And I came across this thing called the Atacama mummy. Y- you probably know that little, that little mummy that was claimed to be, uh, an alien baby.

    7. JR

      Is this the Peruvian one?

    8. GN

      Yes. It was ... no, it was ch- uh, Chilean. This was-

    9. JR

      Oh, okay. So this is the original one?

    10. GN

      The original one.

    11. JR

      Okay.

    12. GN

      Long ago. And so I reached out to the people who were claiming to represent the owner of the thing, and I said-

    13. JR

      What year was this?

    14. GN

      2010, 2011. And I said, "Hey, I can tell you what it is. Why don't you ... you know, I can tell you if it's human or not if you would get me a piece of it's ... uh, you know, first of all, send me some X-rays of the thing." So I did ... the first thing I did with those X-rays was, it turned out that at Stanford we had th- the world's expert who wrote the book on pediatric bone disorders.

    15. JR

      Mm.

    16. GN

      And I brought it to him and I said, "What do you think this is?" And he said, "Hmm, well, I haven't really seen this before, but it could be this gene, this gene, this gene," et cetera. He said, "But here's ..." oh, there it is.

    17. JR

      There it is.

    18. GN

      There it is. Um, yeah. And, um, and so yeah, it looks weird, doesn't it?

    19. JR

      Super.

    20. GN

      And so, um, e- and so the expert told me, "Okay, I need this view of an X-ray, this view, this view, this view." And so we got that and he came back and he said, "Okay, well, you know, we need to get some DNA sequencing," he said. I said, "Okay." So we got a piece of the bone from actually the rib, and the rib was important to use because that would be, I felt, an area that would be least likely to be contaminated by bacterial, you know, cont- you know, degradation. And so I got a little bit of bone marrow out and I did the sequencing. Uh, long story short, I had to bring in ... once I'd done that, there was a lot of DNA that didn't make sense, but it was, it's old DNA. It wasn't that old actually, but it was degraded. So I had to bring in experts at Stanford who knew how to fix th- the degradation. And then I had to bring in an expert in South American genetics, who also happened to be at Stanford. And then we brought in a team of students. And then I brought in Roche, uh, Diagnostics. I had sold a sequencing company to Roche, uh, about two, a few years earlier. So I brought in the team that actually knew how to help me assemble the genome. And then we published a paper which said it's human, uh, it was l- uh, a female, and here are some mutations that it might, that might explain what it looked like. They did have some mutations in, in gene. And then the UFO community hated me because I had disproven th- that as not being a baby, uh, not being an alien. But of course, that picture that you showed, I mean, it was worldwide news and literally the title of one of the things is Stanford Scientist Sequences Alien Baby.

    21. JR

      Uh. (laughs)

    22. GN

      And so, (laughs) um, you know, and so, uh, but the paper stands the test of time. Nobody's disproven what it is that I showed, despite the fact that some people want to say that I was a CIA plant and I was paid off by the CIA, et cetera.

    23. JR

      Uh, of course.

    24. GN

      But what, what that had done was, I- that I didn't realize, but I'd kind of hoped, was that it sent up a flag, um, to a scientific community that already existed that I wasn't aware of, of scientists who were deeply involved with the government in the analysis of UAP that I wasn't privy to. And so literally about a month after, uh, the, um, the j- the, uh, movie came out about that thing, uh-... I got a knock at my door, um, and it was representative of the CIA and an aerospace company, unannounced, and they said, "We wanna talk to you." (sniffs) And they wanted, um, my help with a number of, uh, military and diplomatic personnel who'd been, they claimed, harmed by things. Uh, they'd either heard stuff, et cetera and long story short, the majority of the 100 or so people that I had privy to their medical records ended up being the first of the Havana Syndrome patients.

    25. JR

      Ah.

    26. GN

      Um, they'd heard things in their head, et cetera, but what they had done was they had shown me the data literally that day in my office. They brought out the MRIs, they brought out the X-rays and the damage in the brain, et cetera. It was clear. I mean, it wasn't... it was not just data. It was evidence that something had happened. Uh, it wasn't somebody's story. It was evidence, um, that was repeatable. Um, and so that took us about three or four years to figure out what they were and it was at about the time that actually the Havana events were occurring, that we realized that all the symptoms of what it is that we were seeing in this group of patients were matching what it was that the Havana Syndrome individuals had. So in a way, that was good, because that meant that those 90 or so patients who matched, we could hand over to the national security people and, you know, it became a real thing. And now there's like a DOD website that has anomalous health incidents where people can come forward and report the stuff that they've got, and here is the ways you can use the Veterans Administration to seek medical help. Whereas previously, they'd been shooed away as, "We don't wanna hear about this."

    27. JR

      What do they think it is?

    28. GN

      It's an energy weapon of some kind, a microwave or other energy ... or gamma energy weapon. And that sounds ... okay, that sounds crazy, except no one would admit or no one would deny that we have the capability to do it. It's basically if, if you take the front off your microwave and turn it on and put your face near it, you'll get burned. So this is just a way to direct the microwaves or sound waves-

Episode duration: 2:37:48

Install uListen for AI-powered chat & search across the full episode — Get Full Transcript

Transcript of episode B7y3qcgSRY8

Get more out of YouTube videos.

High quality summaries for YouTube videos. Accurate transcripts to search & find moments. Powered by ChatGPT & Claude AI.