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A Stanford Cancer Scientist on What Actually Prevents Cancer (And What Wellness Headlines Get Wrong) · The LIVING Room Podcast | Inside The WNDR Lab

0:00
SPEAKER_01: Cancer research is not a national good.
0:01
SPEAKER_01: Cancer research belongs to everybody and matters to everybody.
0:05
SPEAKER_01: I think if you sit there and ask in a room of people, has your life been affected by cancer?
0:11
SPEAKER_01: Every hand in the room is gonna go up.
0:12
SPEAKER_01: It matters a lot.
0:14
SPEAKER_01: Am I optimistic?
0:15
SPEAKER_01: I am so optimistic about the science.
0:17
SPEAKER_01: Cancer pulled a trick.
0:19
SPEAKER_01: It hijacked an ancient system to allow rapid genome change.
0:23
SPEAKER_01: And that's why cancers become resistant to our treatments so quickly.
0:27
SPEAKER_01: People with a diagnosis of quote terminal cancer are living with cancer.
0:31
SPEAKER_01: Now that is an extraordinary statement, and it speaks to the value and the importance of cancer research.
0:38
SPEAKER_01: People live with it.
0:39
SPEAKER_01: The most disturbing myth is one that's never specifically stated, but which has an undercurrent, which is if you get cancer, it's your fault.
0:47
SPEAKER_01: It really bothers me.
0:50
SPEAKER_00: I think on the flip side of that as well, that you could do everything right.
0:53
SPEAKER_00: That's right.
0:54
SPEAKER_00: And you have no guarantee.
0:56
SPEAKER_00: If you had any amount of funding, unlimited resources, support, the tools and technologies, what would you like to study?
1:02
SPEAKER_00: What would you like to solve that hasn't yet been solved?
1:05
SPEAKER_01: How do you develop more effective treatments for people whose cancers have extra chromosomal DNA?
1:11
SPEAKER_01: That's priority number one.
1:13
SPEAKER_01: Because that probably affects close to 4 million people a year.
1:17
SPEAKER_01: And people whose cancers have extra chromosomal DNA do worse than all other cancer patients.
1:23
SPEAKER_01: Exercise reduces cancer risk of many different cancer types.
1:28
SPEAKER_01: One of the best tools you can have to reduce your risk of cancer is literally sitting with you.
1:33
SPEAKER_01: You have agency in these matters.
1:36
SPEAKER_01: Do it.
1:57
SPEAKER_00: Now, despite decades of research, trillions of dollars invested, and some really extraordinary scientific progress, it still remains one of the most complex and feared diseases we face.
2:07
SPEAKER_00: But what if part of the challenge is that we've been looking at cancer through the wrong lens?
2:11
SPEAKER_00: What if cancer isn't a single disease at all, but an evolving system, one that adapts, changes, and outmaneuvers us in real time?
2:19
SPEAKER_00: Now, today's guest is one of those scientists that's helping to fundamentally reshape how we understand that system.
2:25
SPEAKER_00: Dr.
2:25
SPEAKER_00: Paul Michel is a physician scientist, a professor of pathology at Stanford University, and is considered one of the world's leading cancer researchers.
2:33
SPEAKER_00: His work has led to one of the most important discoveries in modern oncology, that in many aggressive cancers, the genes driving the tumor growth can actually escape chromosomes entirely, existing as these free-floating circular DNA that allow tumors to evolve at an extraordinary speed.
2:49
SPEAKER_00: Now, this is a discovery that helps to explain why some cancers are so aggressive, why they become so resistant to treatment, and why, despite everything we know, they can still outpace us.
2:59
SPEAKER_00: Now, whilst we unpack the science here and tell you what to do about it, we also talk about the deeply human side of cancer, what drives someone to dedicate their life to it, what it means to live with the diagnosis and how we begin to shift from a mindset of eradication to one of understanding, management, and ultimately prevention.
3:16
SPEAKER_00: This is a conversation about where the future of cancer prevention is heading and how we begin to take power back from a disease that has taken so much from so many.
3:26
SPEAKER_00: Welcome to the living room.
3:27
SPEAKER_00: Well, welcome.
3:28
SPEAKER_00: Thank you for coming.
3:30
SPEAKER_00: Let's start by talking a bit about how you got here because you sit at this interesting intersection of you know medicine, science, and a bit of philosophy.
3:40
SPEAKER_00: Why that path?
3:42
SPEAKER_00: And a secondary question: why did you end up then deciding on you know dedicating your career to cancer prevention and treatment?
3:51
unknown: Great.
3:52
SPEAKER_01: So, first of all, Chris, thank you for inviting me.
3:54
SPEAKER_01: It's really a pleasure to have this conversation with you and to be here.
3:58
SPEAKER_01: Um it's an important question, right?
4:02
SPEAKER_01: We should always ask ourselves, why are we here, right?
4:04
SPEAKER_01: What are we doing?
4:05
SPEAKER_01: And for me, it's it really actually is something that started off quite personally.
4:11
SPEAKER_01: So, to tell you my story, um, I'm a physician scientist and I do cancer research.
4:17
SPEAKER_01: Um, winding it back, it really started because I lost my father to cancer when I was 14 years old.
4:23
SPEAKER_01: He was 51.
4:24
SPEAKER_01: Um, and it was terrible.
4:26
SPEAKER_01: Um, it was just terrible.
4:28
SPEAKER_01: And I remember watching helplessly, basically, as he um painfully died, and I wanted to do something about it.
4:38
SPEAKER_01: And in fact, I'd always loved science.
4:40
SPEAKER_01: My dad was a scholar, he was a philosophy professor.
4:43
SPEAKER_01: Um didn't know that.
4:45
SPEAKER_01: Yeah, he was a philosophy professor, hence why philosophy.
4:48
SPEAKER_01: Um so, you know, he was living the American dream.
4:51
SPEAKER_01: My dad was a Holocaust refugee from Vienna.
4:55
SPEAKER_01: He was actually one of the interpreters for the Dachau trials.
4:58
SPEAKER_01: He came to America, G I Bill, um, becomes a scholar, um, and he's living the American dream.
5:05
SPEAKER_01: And boom, age of 51, and he's gone.
5:10
SPEAKER_01: Uh, and it was it was devastating.
5:13
SPEAKER_01: I think it was especially devastating for him, but it was devastating for me too, as well as for my brother.
5:19
SPEAKER_01: And, you know, I um and I wanted to do something.
5:22
SPEAKER_01: It's funny because my wife, Deborah, um, found my college essay.
5:27
SPEAKER_01: And in it, I said, I want to become a doctor and a cancer researcher to do something about it.
5:33
SPEAKER_01: And there were some wonders along the path, but that's been my North Star.
5:38
SPEAKER_01: Um, and so my professional life has really been dedicated towards that.
5:43
SPEAKER_01: And my path was not a simple, straightforward one.
5:46
SPEAKER_01: First, I went to medical school, literally met Deborah on the first day of it.
5:50
SPEAKER_01: Is that right?
5:51
SPEAKER_00: Yeah, literally.
5:52
SPEAKER_00: So, for context for the listeners, Deborah is also on our scientific council.
5:56
SPEAKER_00: So Deborah's the co co-director of the Stanford Longevity Center.
5:59
SPEAKER_00: Yeah.
5:59
SPEAKER_00: Interesting dinner conversations, no doubt.
6:02
SPEAKER_01: Very much so.
6:02
SPEAKER_00: Yeah.
6:03
SPEAKER_00: Um we'll get into that later.
6:05
SPEAKER_01: Of course.
6:05
SPEAKER_01: And so I um went to medical school and then I trained as a pathologist, really, because I wanted to look the enemy in the eyes.
6:15
SPEAKER_01: And I finished all of my training and realized I'd spend the rest of my life just looking at the enemy and realized I needed to do something about it.
6:23
SPEAKER_01: So then I trained as a scientist.
6:25
SPEAKER_01: And then I um came back, and this was early.
6:29
SPEAKER_01: So I started my first professional um role as an independent uh assistant professor at UCLA in 1998.
6:38
SPEAKER_01: And just to give this context, this was just around the time of the sequencing of the human genome and the idea of precision medicine that you could tailor a therapy for a person based upon their genetics.
6:51
SPEAKER_01: Now, I had gone to a lab of someone who was a very extraordinary scientist who'd been the first person to climb both Everest and K2.
6:58
SPEAKER_01: It's really a his name is Lewis Rikert, remarkable scientist, remarkable teacher.
7:04
SPEAKER_01: And I was doing basic science.
7:06
SPEAKER_01: And here I arrive at the university, and I am um I am putting RNA into frog eggs to study signaling pathways.
7:16
SPEAKER_01: And I came getting called to the OR to diagnose tumors, and I thought, what am I doing?
7:21
SPEAKER_01: Right?
7:22
SPEAKER_01: Shouldn't I be figuring out how to quantify and measure what's going on in these human cancers?
7:28
SPEAKER_01: So I started developing tools to do that.
7:31
SPEAKER_01: And that work took off.
7:33
SPEAKER_01: Uh, and my career grew and I was moving up the food chain.
7:38
SPEAKER_01: And um but there was a problem.
7:42
SPEAKER_01: People weren't getting better for the most part.
7:45
SPEAKER_01: And I kept thinking something was missing.
7:47
SPEAKER_01: And I hope I'm not telling you too meandering a story, but I I want to tell you how it how it got to the discovery that's really changed, I think, an understanding of cancer, um, or at least many cancers.
8:00
SPEAKER_01: And um, so the work was proceeding, but I kept feeling like I was missing something.
8:06
SPEAKER_01: And um at the age of 50, right literally before the age that my father was when he passed away, I told Deborah and our and our daughters, Anna and Sarah, let's go to Paris to do a mini sabbatical over the summer.
8:20
SPEAKER_01: In no small part because I wanted to spend time with my uncle Walter Michel, who was my father's brother.
8:27
SPEAKER_01: And Walter and I connected after my father died.
8:30
SPEAKER_01: And he became a father figure and a mentor and a friend.
8:35
SPEAKER_01: And I wanted to spend time with him.
8:36
SPEAKER_01: And we spent time in cafes in Paris just talking, and I vividly remember him talking with me about the importance of courage and about finding your own voice.
8:47
SPEAKER_01: And I kept thinking, we're missing something.
8:50
SPEAKER_01: And I made two decisions.
8:53
SPEAKER_01: I left the university where I was at, UCLA, and I went to a basic science institute.
8:58
SPEAKER_01: I was the only physician scientist in it, because I wanted time, and I decided to look where the light wasn't shining.
9:05
SPEAKER_01: And that started a path that with a move to Stanford five years ago and a sequence of events that's taken about 12 years, has I think changed our understanding of the fundamental mechanisms of some of the most aggressive forms of cancer.
9:20
SPEAKER_01: And I can tell you about it if you like.
9:23
SPEAKER_00: Absolutely.
9:24
SPEAKER_00: Before we do that, actually, can you given that given that this diagnosis, or we're all gonna hear, or at least around 50% of us perhaps, I don't know, correct me if I'm wrong, are going to either get that diagnosis at some point in our lives, but we're all gonna hear about that, and then we've all probably at some point either have been affected by that with our family or will be.
9:48
SPEAKER_00: Can you at a very high level explain what cancer even is?
9:54
SPEAKER_01: Yes.
9:54
SPEAKER_01: Um, and you're right.
9:57
SPEAKER_01: I think if you sit there and ask in a room of people, has your life been affected by cancer?
10:03
SPEAKER_01: Either you're someone you love or yourself, every hand in the room is gonna go on.
10:08
SPEAKER_00: I agree.
10:08
SPEAKER_01: Right?
10:09
SPEAKER_01: Uh it matters a lot.
10:11
SPEAKER_01: Um and so then what is cancer?
10:14
SPEAKER_01: It used to be one thing when we didn't know much about it, but it turns out it's lots of things.
10:21
SPEAKER_01: And then the world has changed in terms of how we understand it.
10:25
SPEAKER_01: It used to be that the sort of way we would think about cancer was where did it arise?
10:32
SPEAKER_01: Is it a breast cancer?
10:34
SPEAKER_01: Is it a colon cancer?
10:35
SPEAKER_01: Is it a brain cancer?
10:37
SPEAKER_01: And interestingly, that kind of morphologic visual body part description remains a standard.
10:45
SPEAKER_01: When you ask people what kind of cancer is, that's usually the answer that they're going to give you.
10:51
SPEAKER_01: But the ability to interrogate the genes of human beings and their tumors has begun to change the game and provide a completely different level of insight into what cancer actually is.
11:03
SPEAKER_01: Because there are certain commonalities in how cancers come about that might make a cancer of one particular origin more like a cancer of a different type based upon its genes than those that actually look the same under the microscope and might need to be treated differently.
11:21
SPEAKER_01: So we're beginning to start seeing cancers in a different way being driven by alterations in their genes.
11:29
SPEAKER_01: Um, but then that's raised yet another complexity, which is it isn't just a deterministic sense of something going wrong with our genes.
11:39
SPEAKER_01: You can't disentangle our genes from our environments, and there's an interplay with the environment.
11:45
SPEAKER_01: So it's turning out that cancer is a very complex set of diseases that has at least one commonality.
11:53
SPEAKER_01: And that commonality is the fact that the cells in the body are supposed to listen to the central command.
11:59
SPEAKER_01: And in cancer, they have stopped listening to the central command and have gone rogue.
12:04
SPEAKER_01: That's the commonality.
12:06
SPEAKER_01: The reasons that they do it differ sometimes within an individual.
12:10
SPEAKER_01: So that creates a more complex landscape in terms of thinking about how do you diagnose this and how you do you treat it.
12:17
SPEAKER_01: However, the amount of knowledge has moved so quickly, in no small part because of technological advances, that there's a much deeper understanding.
12:27
SPEAKER_01: And there are cancers that arise in certain ways and cancers that arise in others.
12:33
SPEAKER_01: Um, some of the simplest ones are, for example, and I don't mean to say that they're simple, but for example, virally developed cancers like human papillomavirus or cancers that arise from hepatitis.
12:45
SPEAKER_01: We understand those.
12:46
SPEAKER_01: Certain cancers we know come from germline, or meaning inherited defects like breast cancer and ovarian cancer that come from BRCA lesions or lynch syndrome with mutations that happen in colon cancer.
13:01
SPEAKER_01: But most cancers seem to arise out of the blue, and we've got a much deeper understanding of the genetic basis of those and increasingly how the environments might interact with the genetics to cause those cancers.
13:14
SPEAKER_00: I can ask you what might be a really naive question.
13:17
SPEAKER_00: There's going to be a few of these.
13:18
SPEAKER_00: Um Why are there some cancers that are incredibly aggressive and some that are not?
13:25
SPEAKER_00: And you know, and you know, there are malignant tumors, benign tumors, there are um certain cancers with high mortality rates, one with very low mortality rates.
13:37
SPEAKER_00: Isn't that a really stupid question?
13:39
SPEAKER_01: It's not a stupid question, and it's one that still perplexes and challenges many of us in the field.
13:45
SPEAKER_01: But let's try to break it down.
13:47
SPEAKER_01: So, why are some cancers so much more aggressive than other cancers?
13:51
SPEAKER_01: Well, one reason is that cancers that are harder to detect earlier are more difficult to treat.
13:58
SPEAKER_01: So if you look at, for example, glioblastoma, the most common brain cancer, or pancreatic cancer, you really can't detect those things earlier.
14:08
SPEAKER_01: So the mortality rates are very poor because they've progressed so much more aggressively by the time that you find them, which really leads into a discussion about early detection, right?
14:17
SPEAKER_01: But if you look at certain cancers where we screen, for example, um, you know, things like colonoscopies and things like that.
14:25
SPEAKER_01: Prostate, right?
14:26
SPEAKER_01: Prostate uh people in general do better.
14:29
SPEAKER_01: But that's not the whole story.
14:32
SPEAKER_01: There's intrinsic biology.
14:33
SPEAKER_01: So what we discovered is uniformly associated with poor outcome in patients because the biology is so different in those cancers.
14:41
SPEAKER_01: So there are both, I would say, external reasons in terms of when we catch those cancers, and there are internal reasons in terms of the biology itself that makes them more aggressive.
14:54
SPEAKER_00: Let's talk about that because you know, I was a little familiar with your work.
14:58
SPEAKER_00: Obviously, we've worked together for a couple of years now, but this concept that um, you know, there's more at play with your DNA than we believe when it comes to the the sort of growth and and aggressiveness of the cancer itself and EC DM DNA, I believe I'm saying that.
15:18
SPEAKER_00: You're saying it right.
15:18
SPEAKER_00: Um I was kind of fascinated about the idea that not only does that sort of add fuel to the fire, but it kind of tears down the smoke alarm as well.
15:29
SPEAKER_00: Can you can you maybe unpack that and help the audience understand what that's I I can.
15:33
SPEAKER_01: Um what you're referring to, this EC DNA, is called extra chromosomal DNA.
15:39
SPEAKER_01: And let me give a a backstory to what it means, how we found it, and what we've learned about it.
15:46
SPEAKER_01: So the backstory is, you know, when we think about genes, we think about chromosomes.
15:51
SPEAKER_01: I mean, it's it's imprinted in our heads, right?
15:53
SPEAKER_01: You look at a box of 23andMe, you know, we're always thinking of chromosomes, right?
15:58
SPEAKER_01: That's how genes are inherited.
15:59
SPEAKER_01: That's how genetic information goes from parents to their children, or when a cell divides, it goes on chromosomes.
16:07
SPEAKER_01: Um and so that's really the basis of pretty much everything we know about human genetics.
16:13
SPEAKER_01: So anything that is not within that line of thinking is kind of banished.
16:17
SPEAKER_01: We just we we wouldn't even think about it.
16:20
SPEAKER_01: And what we discovered in the about close to 20% of all people with cancer, and probably more in those uh in which it's later stage and metastatic, is that the cancer-causing genes have jumped off chromosomes onto circular pieces of DNA.
16:38
SPEAKER_01: So, why does that matter?
16:40
SPEAKER_01: It's because they've untethered themselves from the normal constraints of how genetic information is passed.
16:47
SPEAKER_01: So, let me give an example about why it actually matters and then maybe why we missed it until now.
16:54
SPEAKER_01: And interestingly, it had been seen, but not understood.
16:58
SPEAKER_01: So let's go back and say what does this actually mean?
17:00
SPEAKER_01: So let's just say you had three copies of a gene on chromosomes.
17:05
SPEAKER_01: Um, when the cell was getting ready to divide, normally what happens is you duplicate it.
17:10
SPEAKER_01: So you got six, and each daughter cell would get three.
17:14
SPEAKER_01: But these circular pieces of DNA don't have the same machinery that chromosomes have.
17:19
SPEAKER_01: So those three become six, but instead of going three and three, it could be six and zero, or five and one, or four and two, or three and three.
17:29
SPEAKER_01: So think about this on one thing.
17:30
SPEAKER_01: You're you're supposed to get two copies, but now a cell got four, right?
17:35
SPEAKER_01: And now if that's advantageous, that four is going to become eight.
17:39
SPEAKER_01: Sure.
17:39
SPEAKER_01: And now you keep getting the spread.
17:41
SPEAKER_01: So what two things are happening at the same time.
17:44
SPEAKER_01: You're making extra copies of a gene that's promoting cancer, and you're creating variation, which Darwin taught us is the fuel for evolution.
17:53
SPEAKER_01: You have a landscape to select the likelihood that a cell that is more fit is sitting right there.
17:59
SPEAKER_01: So it's almost as if we can learn something from nature because, in fact, that's exactly what bacteria do.
18:07
SPEAKER_01: Bacteria have circular genomes and they have plasmids.
18:11
SPEAKER_01: And daughter cells, each daughter is a unique organism, and daughter cells don't have to have the same DNA as mother cells.
18:18
SPEAKER_01: And consequently, the species evolves very quickly.
18:22
SPEAKER_01: That's why we struggle with bacterial antibiotic resistance.
18:25
SPEAKER_01: But this would have been unthinkable in human cancer.
18:29
SPEAKER_01: Wait, they're supposed to have chromosomes.
18:31
SPEAKER_01: It is as if cancer pulled a trick, it hijacked an ancient system to allow rapid genome change.
18:39
SPEAKER_01: And that's why cancers become that have this become resistant to our treatments so quickly.
18:45
SPEAKER_00: So is that is it effectively, you know, as they the cells divide, they're just rolling the dice.
18:50
SPEAKER_01: Exactly.
18:51
SPEAKER_01: Every cell division is a dice roll.
18:55
SPEAKER_00: Does that make it harder to track, treat, yes, makes it much more aggressive, I assume, than evasive?
19:02
SPEAKER_01: That the yes it does.
19:04
SPEAKER_01: And so the last 12 years have been about tracking that down.
19:08
SPEAKER_01: So if you don't mind, I'd like to tell you the story of how it came about and what we learned.
19:12
SPEAKER_01: So basically, I was trying to understand something.
19:14
SPEAKER_01: This goes back to that conversation I was telling you about with my uncle Walter in Paris and looking where the light wasn't.
19:22
SPEAKER_01: I was trying to understand something, which was there was a particular cancer that we were studying, glioblastoma, this horrible brain cancer, that frequently has many copies of an oncogene, amplified copies called epidermal growth factor receptor.
19:36
SPEAKER_01: It's a very strong growth-promoting gene.
19:38
SPEAKER_01: So in cancer, it's not just mutations in the sequence, but if you have extra copies, they can drive that cancer.
19:46
SPEAKER_01: And we were trying to understand why don't they respond to drugs that target it?
19:50
SPEAKER_01: Everything we learned about precision medicine says it should work, but it didn't.
19:54
SPEAKER_01: And there were a couple of things about it that were strange.
19:57
SPEAKER_01: Every cell in the tumor wasn't the same.
19:59
SPEAKER_01: Some cells had a little, some cells had a lot.
20:02
SPEAKER_01: And what we had learned about classical genetics says that if you treated the tumor, you might get rid of the cells with a, with, you know, a lot, for example, and save the ones that had a little, but it's a slow process, right?
20:15
SPEAKER_01: But what we discovered is that they changed in a way as we expected, but it was way too fast.
20:22
SPEAKER_01: And it got even stranger.
20:23
SPEAKER_01: If you took a cell that had a little or a cell that had a lot, and you put it into a dish or you put it into a mouse, they all gave rise to the original tumor with its full spectrum.
20:34
SPEAKER_01: And that made no sense by classical genetics.
20:36
SPEAKER_01: And then I realized something.
20:38
SPEAKER_01: How do we actually know where genes are?
20:40
SPEAKER_01: So, you know, billions of dollars had actually been spent because the human genome had been sequenced, right?
20:46
SPEAKER_01: So we know where all of the genes are on human chromosomes.
20:50
SPEAKER_01: They'd been mapped, right?
20:51
SPEAKER_01: And then sequencing technologies had changed the game.
20:55
SPEAKER_01: You could take the DNA from a tumor and you could sequence that DNA.
20:59
SPEAKER_01: And now you get these reads, you know, 250 base pairs, and you map them back to the map.
21:05
SPEAKER_01: But what I began to realize was uh the map comes from normal cells.
21:11
SPEAKER_01: It assumes that things are in a cancer cell where they are in a cell.
21:17
SPEAKER_01: But people hadn't really looked.
21:18
SPEAKER_00: So the map was wrong.
21:19
SPEAKER_01: The map was wrong for these cancers, and then began to to look at this carefully.
21:24
SPEAKER_01: And it turns out when we began to look under a microscope, where you can tell where genes are when a cell is dividing, we began to see that they weren't on chromosomes.
21:34
SPEAKER_01: Now, this had been seen 60 something years before, but not completely understood.
21:40
SPEAKER_01: In fact, not understood well at all.
21:42
SPEAKER_01: And people had begun brilliant people, you know, talk about standing on the shoulders of giants.
21:47
SPEAKER_01: Brilliant people had begun working on this.
21:49
SPEAKER_01: But as the technologies changed, that knowledge disappeared completely.
21:55
SPEAKER_01: And when we published the first paper on this in science in 2014, it was to a colossal.
22:00
SPEAKER_01: Scratching of heads.
22:01
SPEAKER_01: And I remember talking to people and they'd say, Well, that's an odd one.
22:05
SPEAKER_01: You know, the cancer-causing gene I study, it's on chromosome eight.
22:08
SPEAKER_01: And I'd say, How do you know?
22:10
SPEAKER_02: Yeah.
22:11
SPEAKER_01: And then they would pull out a cancer genome atlas map, and all I could think of was Ptolemy's map of the solar system.
22:17
SPEAKER_01: You know, the measurements were right, but the map was wrong.
22:20
SPEAKER_02: Yeah.
22:20
SPEAKER_01: You know, and maybe that was what was happening.
22:22
SPEAKER_01: So the last 12 years have been about proving it, demonstrating it, trying to understand it, and figuring out how to drug it.
22:32
SPEAKER_01: And that's been done with many amazing and generous colleagues and collaborators.
22:36
SPEAKER_00: And is it working?
22:38
SPEAKER_01: You know, is it this is what we know, right?
22:41
SPEAKER_01: Um, now people have begun to recognize that this is incredibly important science.
22:47
SPEAKER_03: Yeah.
22:48
SPEAKER_01: Um, and people all over the world are working on it.
22:51
SPEAKER_01: It's been highlighted in Nature, Science, New England Journal of Medicine, uh, Cancer Discovery, people recognized it.
22:59
SPEAKER_01: And the important thing is the field is expanding.
23:02
SPEAKER_01: Brilliant people from all over the world are working on it.
23:05
SPEAKER_01: Two companies have been formed.
23:07
SPEAKER_01: There will almost certainly be more.
23:10
SPEAKER_01: Have people figured out how to drug this yet?
23:12
SPEAKER_01: No.
23:12
SPEAKER_01: Are people trying?
23:14
SPEAKER_01: Very much so.
23:15
SPEAKER_01: I have um great sense of purpose and optimism that this extraordinarily intelligent community will figure out how to do it.
23:24
SPEAKER_01: Can we detect it?
23:26
SPEAKER_01: Can we detect it early?
23:27
SPEAKER_01: Because we've learned it doesn't only happen late in the development of a cancer, it can happen early in a pre-cancer.
23:33
SPEAKER_01: So, for example, they we looked to try to understand if you take people who are predisposed to getting a cancer, like people with Barrett's esophagus, where there's a low rate, but not an impossibility, in fact, a real possibility over a lifetime that they might end up getting an esophageal cancer.
23:53
SPEAKER_01: So we looked, and working with collaborators at the Fred Hutch and at Cambridge University, um, we could look.
24:01
SPEAKER_01: Do you see the development of this ECDNA before it comes a cancer in something called dysplasia, where the cells are not looking right and they might become a cancer?
24:10
SPEAKER_01: And lo and behold, we could see it.
24:12
SPEAKER_01: And if it was there, those people would go on to get cancer.
24:16
SPEAKER_01: And so that's telling us that this is a transformative event.
24:19
SPEAKER_01: And our colleague here in New York at Memorial's Long Kettering, Andrea Ventura, has figured out how to genetically model it in mice.
24:25
SPEAKER_01: And indeed, it causes cancer.
24:27
SPEAKER_01: And so that says, hey, we need to be on the lookout.
24:30
SPEAKER_01: So people are thinking very hard.
24:32
SPEAKER_01: Could we find ways to detect this much earlier, perhaps even in the blood?
24:37
SPEAKER_01: And I think that's going to become important as is figuring out how to develop treatments that are targeting it.
24:43
SPEAKER_00: You've spoken in the past about um making a comparison to the ongoing treatment of things like heart disease and diabetes, and making that comparison to certain cancers, and that maybe it's not about curing these things, but being able to treat them such that we can live with them.
25:02
SPEAKER_00: Can you speak to that for a moment?
25:04
SPEAKER_01: I think it's actually an incredibly important point.
25:06
SPEAKER_01: You know, cancer is so terrifying to us that we we must get rid of it.
25:12
SPEAKER_01: You can't live with it.
25:13
SPEAKER_01: You must eradicate it, get it out, right?
25:16
SPEAKER_01: Cure it, get it out.
25:17
SPEAKER_01: But we just don't talk about most other diseases in that way.
25:21
SPEAKER_01: We talk about managing them, right?
25:23
SPEAKER_01: You know, living with them.
25:25
SPEAKER_01: And that might mean living symptom-free too.
25:28
SPEAKER_01: But we don't sit there and talk about eradicating their existence.
25:31
SPEAKER_01: We set an extraordinarily high bar on cancer on that.
25:36
SPEAKER_01: Now, what's fascinating to me is if you sort of look back at what's happened in the past and look at where we are now, you can already start seeing green shoots coming up in that respect.
25:48
SPEAKER_01: I'll give an example, right?
25:50
SPEAKER_01: Um there was, and I'll come, I'll go back to my father on this one.
25:54
SPEAKER_01: I remember at the age of 14, you know, there he was in the hospital on his way out, right?
26:00
SPEAKER_01: And he asked for, you know, ice.
26:02
SPEAKER_01: So I went to the nurses station and there was his chart.
26:05
SPEAKER_01: And on it, in big red letters, it said terminal, right?
26:08
SPEAKER_01: And I knew what that meant.
26:10
SPEAKER_01: Now, there was an article in the Wall Street Journal a few months ago that people with a diagnosis of quote terminal cancer are living with cancer.
26:19
SPEAKER_01: Now, that is an extraordinary statement, and it speaks to the value and the importance of cancer research, right?
26:26
SPEAKER_02: Yeah.
26:26
SPEAKER_01: That's changing the game.
26:28
SPEAKER_01: I mean, diseases that meant that a person wouldn't live at all.
26:33
SPEAKER_01: Now people live with it.
26:35
SPEAKER_01: My hope, of course, we'd like to cure many cancers, but I think many people would take, I can live with it, right?
26:43
SPEAKER_01: I want to go on and live my life and be with my family and be with my, you know, do the work and you know, enjoy the life that I want to have.
26:53
SPEAKER_01: People would take it, right?
26:54
SPEAKER_00: And it's no longer a death sentence, a diagnosis, whereas we used to think there was, right?
26:59
SPEAKER_00: And in many cases, it was.
27:00
SPEAKER_01: That's right.
27:00
SPEAKER_01: And people would feel like pariahs, you know, yeah, like it was something that was transmissible, you know.
27:05
SPEAKER_01: And I think it's really important to rethink that and to have to give people a sense of living with it.
27:11
SPEAKER_01: Of course, you'd rather not get it.
27:14
SPEAKER_01: But if people get it, can we find ways to manage it so that people can live with it?
27:19
SPEAKER_00: Can I ask you two questions on that?
27:20
SPEAKER_00: One, if if we are successful in what we're aiming to achieve, you know, if we could get 100 healthy years for everyone, if we lived long enough, would we always develop cancer?
27:32
SPEAKER_00: I've I I don't know if I've completely misinformed here, but I I heard that if you, you know, all men after a certain amount of time would eventually develop prostate cancer.
27:41
SPEAKER_00: Or is that right?
27:42
SPEAKER_01: Or am I just.
27:45
SPEAKER_01: But there there's there's two interesting parts to that.
27:47
SPEAKER_01: Let's deal with the prostate part second.
27:50
SPEAKER_01: Okay.
27:50
SPEAKER_01: And let's deal with the other part first.
27:52
SPEAKER_01: So what's really interesting is you used to think that cancer was just boom, it happens.
27:56
SPEAKER_01: And I think in some instances, it's not exactly a boom, maybe it's an event followed by a boom.
28:02
SPEAKER_01: But for many cancers, what it really is is a stepwise series of events where you get mutations that sort of advantage a set of cells.
28:14
SPEAKER_01: Now, those cells are waiting to get the next mutations and they're proliferating or reproducing their DNA more rapidly, they're at risk of the next event.
28:27
SPEAKER_01: And of course, the environment might be contributing to some of those people.
28:31
SPEAKER_01: Work from Charlie Swanton, for example, about the interplay between um particulates that come from smoking and pollution and the development of lung cancer through genetics is very compelling, right?
28:42
SPEAKER_01: Um, and and people like Alan Balmain and and such that, you know, uh, and even the deep sequencing from Inigo Martin Corinna and Peter Campbell and Mike Stratton, when you start looking, we're loaded with mutations, right?
28:56
SPEAKER_01: We all are loaded with mutations.
28:58
SPEAKER_01: Does that mean we're going to get cancer?
29:00
SPEAKER_01: Not necessarily.
29:02
SPEAKER_01: Does the chance increase if you make it to 100?
29:06
SPEAKER_01: Maybe, but statistically you'd say yes.
29:09
SPEAKER_01: But there may be people who seem to have more protective mechanisms genetically, andor maybe, and this was what gives me hope, maybe there's things that we actually can do in our lives that reduce our risk for those matters.
29:23
SPEAKER_01: Let's go to the prostate cancer side, right?
29:25
SPEAKER_01: So there's certain cancers that are just like if you look at men over 80 and stuff, and you were just biopsy, they're prostates, which you wouldn't, right?
29:33
SPEAKER_01: But lots of people would have these low-grade cancers that, I mean, they wouldn't even behave like cancers, you know, they'd be diagnosed or classified.
29:41
SPEAKER_01: Are they meaningful cancer?
29:42
SPEAKER_01: Not really, right?
29:43
SPEAKER_01: Um, and so now this is a whole other aspect that if you start diagnosing things in people because you see abnormalities and you stick a needle in and you start seeing things that look suspicious, but you have no idea whether they would just sit there forever.
29:59
SPEAKER_01: It's a Pandora's.
30:01
SPEAKER_01: It's a Pandora's box on these.
30:03
SPEAKER_01: So I think the answer is it's very unclear.
30:05
SPEAKER_00: Well, I think we can unpack that piece when it comes to the the diagnosing of these things.
30:09
SPEAKER_00: One one other question before we move on to how to uh how to create strategies to prevent this happening is we're seeing this worrying rise in cancers in younger people, right?
30:22
SPEAKER_00: Is that is that a product of lifestyle?
30:26
SPEAKER_00: Is it a product of environment?
30:29
SPEAKER_00: Is it something we don't know yet?
30:30
SPEAKER_00: It seems kind of concerning.
30:32
SPEAKER_01: It is concerning.
30:33
SPEAKER_01: And it's an area of intense focus.
30:36
SPEAKER_01: Um, people are thinking hard about it.
30:38
SPEAKER_01: I'm um co-chairing this year's um American Association for Cancer Research meeting.
30:44
SPEAKER_01: I'm co-chairing it with Dr.
30:45
SPEAKER_01: Alice Shaw from Dana Farbor.
30:48
SPEAKER_01: Um, and that's going to be an area of focus during the meeting because people don't actually know uh why is it that we're seeing it?
30:57
SPEAKER_01: You can come up with many plausible explanations.
31:00
SPEAKER_01: For example, um, stress can be related to inflammation in the colon.
31:05
SPEAKER_01: There's no, there's no doubt that stress and colon inflammation can co-occur.
31:13
SPEAKER_01: Is that related to cancer?
31:14
SPEAKER_01: Who knows?
31:15
SPEAKER_01: Yeah, right.
31:16
SPEAKER_01: There's a lot of unanswered questions here.
31:18
SPEAKER_01: Diet, right?
31:19
SPEAKER_01: Does what we eat very likely will play a role?
31:24
SPEAKER_01: How?
31:24
SPEAKER_01: We don't know.
31:25
SPEAKER_01: So the bottom line is it's an open area of immensely important research activity.
31:31
SPEAKER_00: Yeah.
31:32
SPEAKER_00: We've spoken about this many times, but I think that is the the the overarching need for us to get more funding, capture more data, do more human phenotyping so that we begin to understand how those verticals impact not only disease and illness, but the prevention of disease, disease and illness in general.
31:52
SPEAKER_00: Last question before we move on.
31:54
SPEAKER_00: Is the global mortality rate for cancer still on the decline?
32:00
SPEAKER_00: And does that correlate with incidence or is it we're just doing better testing?
32:05
SPEAKER_00: What how is that looking?
32:06
SPEAKER_00: Or do we not actually?
32:07
SPEAKER_01: I think it's not an easy thing to answer because it depends on who you look at.
32:13
SPEAKER_01: Yeah, right.
32:14
SPEAKER_01: You know, so those who are essentially included in those studies are the ones who you see who likely are in a position who are getting better health care.
32:24
SPEAKER_01: So I think it's not a simple way to answer that question.
32:28
SPEAKER_01: I mean, one thing's for sure.
32:30
SPEAKER_01: You decrease smoking, you decrease cancer risk.
32:33
SPEAKER_01: That's for sure contributing.
32:35
SPEAKER_01: But I think the burden of cancer misery across the world, oh boy.
32:40
SPEAKER_00: Yeah.
32:41
SPEAKER_00: Do you think we have a cure cancer?
32:44
SPEAKER_00: I mean, I and the reason I know that's a loaded question, but you know, we've seen some promise with these vaccines for not only prevention, but for treatment and management.
32:54
SPEAKER_00: Yeah.
32:55
SPEAKER_01: Do I think it'll be possible to cure?
32:58
SPEAKER_01: Uh yeah.
32:59
SPEAKER_01: At least from the standpoint of being completely disease-free.
33:03
SPEAKER_01: Because we already see examples of it.
33:05
SPEAKER_01: Sure.
33:05
SPEAKER_01: Right.
33:05
SPEAKER_01: I think the answer is yes, I do.
33:08
SPEAKER_01: And, you know, the other thing is, of course, the earlier you can go, the more likely you are to cure.
33:13
SPEAKER_00: Yeah.
33:14
SPEAKER_00: And, you know, we we sp we've spoken about this on many episodes about you know being very optimistic and bullish about what is coming because we're just seeing the research develop, the technology develop, the the uh diagnosing and um data collection develop, but we all still have this bridge to cross, right?
33:32
SPEAKER_00: And so I think so much about what we want to give the audience and listeners to this podcast is actual tools that we know we can use today.
33:41
SPEAKER_00: That's right.
33:41
SPEAKER_00: Right.
33:41
SPEAKER_00: And and so let's move on to that as a as a as the next section.
33:46
SPEAKER_00: Um, we had uh Dr.
33:47
SPEAKER_00: Gary Miller on recently from Columbia, who's an exposome researcher, and we were talking about all of these specifically about the environment and toxins and pollutants.
33:59
SPEAKER_00: Am I correct in saying there's some pretty compelling evidence that those are contributing to the early stage development of these cancers?
34:07
SPEAKER_01: Yes.
34:08
SPEAKER_01: I think there are compelling data to suggest that.
34:11
SPEAKER_01: Absolutely.
34:12
SPEAKER_01: I mean, the most obvious one is smoke, right?
34:15
SPEAKER_01: Smoking.
34:16
SPEAKER_01: There's no doubt about that.
34:17
SPEAKER_01: And there are others.
34:18
SPEAKER_01: I think the answer is yes.
34:20
SPEAKER_00: Something I find just really hard to come to terms with is that that to me would indicate then that there are a lot of things that are controllable but outside of our control as individuals.
34:33
SPEAKER_00: And this socioeconomic divide, like depending on the zip code that you were born, like that to me is tough to reconcile with.
34:42
SPEAKER_01: I think it's very tough to reconcile with the human cost, the ethical aspects of it.
34:49
SPEAKER_01: It's very uh difficult to reconcile.
34:53
SPEAKER_01: And, you know, research, there's incredible research that's going on that looks at the expososome, right?
35:00
SPEAKER_01: And exposures that people have based upon where they live.
35:03
SPEAKER_01: Um, and the data are disturbing.
35:06
SPEAKER_01: Um, big differences.
35:08
SPEAKER_01: And, you know, part of the mortality differences are not only in causation, but what happens when a person is diagnosed.
35:15
SPEAKER_01: Sure.
35:15
SPEAKER_01: You know, huge differences in what's available to people when they're when they're diagnosed to cancer.
35:21
SPEAKER_01: So there's there are real questions about what's right and what's fair, you know, that have to be addressed because you have, you know, health care is a right.
35:31
SPEAKER_01: Yeah.
35:32
SPEAKER_01: You know, and the idea that you should, everybody deserves the basic human dignity of being taken care of, and that if you have cancer, you need to be taken care of, and that you need to have, you know, the best shot that you can actually have.
35:46
SPEAKER_01: I I'm in complete agreement with you.
35:48
SPEAKER_01: Um, I mean, what's fascinating is that again, the tools drive the knowledge.
35:53
SPEAKER_02: Yeah.
35:53
SPEAKER_01: And the ability to study not just lab animals, but people is changing the game.
36:01
SPEAKER_01: Because now you can start seeing signatures of environmental exposures in people's tumors that are telling you, boy, if that's not a smoking gun, I don't know what is, right?
36:11
SPEAKER_01: And it's telling you this stuff is real.
36:13
SPEAKER_01: So, you know, you come back to this issue of agency.
36:16
SPEAKER_01: What can you do?
36:17
SPEAKER_01: Right?
36:17
SPEAKER_01: What can you as a human being do to reduce your risks of cancer?
36:22
SPEAKER_01: And I think there are things that you can do.
36:24
SPEAKER_00: Tell us, Paul.
36:25
SPEAKER_01: Okay.
36:26
SPEAKER_01: I talked to the members of my lab about this.
36:28
SPEAKER_01: I sort of said, so, you know, if if you're the doctor and a patient comes in to you and says, you know, doc, um, I don't want to get cancer.
36:35
SPEAKER_01: What should I do?
36:36
SPEAKER_01: Okay.
36:36
SPEAKER_01: So you might say, um, don't smoke, right?
36:41
SPEAKER_01: Be a good weight, uh, um, eat a good diet, um get your vaccines um and pick your parents wisely.
36:52
SPEAKER_01: Yeah.
36:53
SPEAKER_01: You know, I mean now is there more to it than that?
36:56
SPEAKER_01: I sure think so.
36:57
SPEAKER_01: So what are the things that we do know?
37:00
SPEAKER_01: So there is really a massive amount of correlational data.
37:06
SPEAKER_01: So causative, not yet exactly, but correlational associative data, that exercise reduces cancer risk of many different cancer types.
37:17
SPEAKER_01: Why it does isn't yet known.
37:19
SPEAKER_01: You can come up with some very good hypotheses.
37:21
SPEAKER_01: If you exercise, you're at a better weight.
37:24
SPEAKER_01: If you're exercise, you're largely taking care of your other health habits.
37:28
SPEAKER_01: If you exercise, you're probably eating better.
37:30
SPEAKER_01: If you exercise, you might be doing it with other people and having social connectivity.
37:34
SPEAKER_01: It almost doesn't matter because it basically says one of the best tools you can have to reduce your risk of cancer is literally sitting with you.
37:46
SPEAKER_01: You have agency in these matters.
37:49
SPEAKER_01: Do it.
37:50
SPEAKER_01: A second thing is what we eat matters a lot.
37:54
SPEAKER_01: These processed foods are really not good for people.
37:58
SPEAKER_01: A third is smoking.
37:59
SPEAKER_01: I'm there's just no doubt about that.
38:02
SPEAKER_01: Overconsumption of alcohol, you know, I mean, heavy drinking is a serious problem.
38:09
SPEAKER_01: Um, and interestingly, I don't think everyone's really looked that carefully at it, but one can't help but think that psychological stress and social isolation, they're clearly bad for your health.
38:22
SPEAKER_01: How they're connected to cancer, nobody really has a clue, but many people have a thought.
38:27
SPEAKER_01: I wonder if, I wonder if.
38:30
SPEAKER_01: So then so what's rational, right?
38:32
SPEAKER_01: What's rational is um preventive screening, right?
38:37
SPEAKER_01: Uh for sure, because you can do something about it to exercise for sure, uh, healthy diet, uh, whole foods, not processed foods, um, engagement with other people, particularly doing things for other people.
38:54
SPEAKER_01: You know, I think I mentioned vaccines and staying away from things that you know are really detrimental.
38:59
SPEAKER_01: You know, that's a lot of agency, yeah, actually, you know, and and then for people who have cancer, the data are even stronger that exercising while you're going through treatment will make it more likely that you do better with the disease.
39:15
SPEAKER_01: I mean, that's a remarkable set of findings.
39:18
SPEAKER_00: You know what I love about that list?
39:20
SPEAKER_00: And these are all things that um not coincidentally uh improve every other aspect of your physiology and biology and cognition.
39:28
SPEAKER_00: The thing I love about that is specifically for cancer, you know, even if you were to include all of these other sort of silver bullet solutions that people might be coming up with, we still have the most robust evidence for the things that we do have agencies for, the things that we can control.
39:44
SPEAKER_00: That's right.
39:44
SPEAKER_00: And the thing that I'm most excited and optimistic about in the field in general is one, we are getting better at capturing metrics from our own biology in real time.
39:55
SPEAKER_00: And it's becoming much more affordable, much more scalable.
39:59
SPEAKER_00: And we now have the tools and technology to be able to approach those things with a scalpel rather than a sledgehammer.
40:06
SPEAKER_00: And we've done some of those today, right?
40:07
SPEAKER_00: And like that's right, we know how to, how do we squeeze more juice out of the lemon that is exercise or nutrition or or um or or human relationships?
40:16
SPEAKER_00: And so that, and that I think is going to be something that is accessible to everyone very quickly, if not already.
40:21
SPEAKER_01: That's right.
40:22
SPEAKER_00: Yeah.
40:22
SPEAKER_01: Um, I also think identification of high-risk individuals will turn out to be increasingly important because, you know, it doesn't mean your destiny if you come from a cancer-prone family.
40:36
SPEAKER_01: There's things that you can do about it, right?
40:38
SPEAKER_01: And so certain people may simply need more diligence and more care.
40:43
SPEAKER_00: So the this was actually something that Gary mentioned last week was you know, genetic loads the gun, the environment pulls the trigger.
40:50
SPEAKER_00: And I think that's a really powerful analogy.
40:53
SPEAKER_00: You know, we we get dealt at hand and we have to do what we can to optimize for it.
40:59
SPEAKER_01: But you know, we we we have no trouble talking about that with heart disease.
41:02
SPEAKER_00: Sure.
41:02
SPEAKER_01: Yeah.
41:03
SPEAKER_01: You know, okay, this is your family's genetics, you know, okay.
41:06
SPEAKER_01: How are you going to live your life to reduce your risk?
41:09
SPEAKER_00: I j it's weird that the just the the concept of heart disease, the term just doesn't feel as frightening as the word cancer, but yet more people end up dying from it.
41:18
SPEAKER_01: I I was I was I'm thinking the same as you.
41:21
SPEAKER_01: But I think it's because people have historically died painfully from cancer while they're being tortured with it.
41:31
SPEAKER_02: Yeah.
41:31
SPEAKER_01: Right?
41:32
SPEAKER_01: With the with the treatments.
41:33
SPEAKER_01: And so I think it is a in the face of immense technological innovation, there's room to really change this landscape.
41:44
SPEAKER_01: You can already see ways that it's changing the landscape.
41:47
SPEAKER_01: I mean, you know, for example, some of the treatments that are bringing the immune system or, you know, radioligand therapies, for example, in prostate cancer, they really have a major effect on people's lives.
42:01
SPEAKER_01: And I think we're just at the beginning.
42:03
SPEAKER_01: And, you know, sometimes my head spins in a really good way when I look at the power of technologies that are being developed.
42:11
SPEAKER_01: You can't stop science.
42:13
SPEAKER_01: I mean, it's a it's an amazing thing.
42:14
SPEAKER_00: And I'm thinking that would have been a great name for the podcast.
42:17
SPEAKER_01: You can't stop science.
42:18
SPEAKER_01: You can't stop science, right?
42:19
SPEAKER_01: And nor should anybody want to.
42:22
SPEAKER_01: And we're in an era.
42:23
SPEAKER_01: I just have to bring this in, Chris.
42:25
SPEAKER_01: We're in an era where the importance of collaboration, global collaboration, unselfishness is not being recognized.
42:39
SPEAKER_01: You know, we're gonna make progress against these this disease by working together, by sharing credit, by working with partners across the globe, by sufficiently funding the study because it affects everybody, you know, and that's under threat right now.
42:56
SPEAKER_01: And so more than ever, right?
42:59
SPEAKER_01: At and at exactly the time when the capability to change the landscape is right within our grasp.
43:06
SPEAKER_01: I feel passionately about this because I mean, look at, you know, in my own example, right?
43:11
SPEAKER_01: We went from an observation that my lab made to now a global team funded by the Cancer Grand Challenges program, where every single paper has multiple first authors, every single paper has multiple senior authors, everybody collaborates, and the secret sauce are the trainees who bridge all of the labs.
43:31
SPEAKER_01: And guess what?
43:32
SPEAKER_01: The field moves at light speed because of it.
43:34
SPEAKER_01: It's a model of cooperation and collaboration, and it does not fall into any of the traditional funding models.
43:41
SPEAKER_01: God bless Cancer Grand Challenges, you know, that allows us to do this, you know, jointly funded by Cancer Research UK and the National Cancer Institute.
43:48
SPEAKER_01: Because the old models of how we do business don't work anymore.
43:53
SPEAKER_01: And we have to be really forward thinking about funding it.
43:56
SPEAKER_01: If we want to give our fellow human beings And ourselves, what we actually deserve.
44:02
SPEAKER_00: Yeah.
44:02
SPEAKER_00: And I think that applies across all of the domains of biology, in fact.
44:06
SPEAKER_00: Yeah, I'd agree.
44:06
SPEAKER_00: You know, we we and it's the reason this business exists.
44:09
SPEAKER_00: I agree.
44:10
SPEAKER_00: You know, to create that collaboration, because we don't know everything about science.
44:14
SPEAKER_00: And there's a lot of questions that we know we want the answers to, but we haven't got the you know funding or or collaboration to answer them yet.
44:22
SPEAKER_00: And I think that's something that's very, really important for listeners of this.
44:27
SPEAKER_00: But like anyone who spends their time on any kind of social media is that there's still more questions unanswered than there are answered, I would wager.
44:34
SPEAKER_01: That's right.
44:34
SPEAKER_00: Yeah.
44:35
SPEAKER_01: That's right.
44:35
SPEAKER_01: It's not an engineering problem.
44:37
SPEAKER_00: Yeah.
44:38
SPEAKER_01: Oh, if we just now we just get a bunch of people together and turn the crank and we'll cure cancer.
44:45
SPEAKER_01: Oh, how I wish that were true.
44:47
SPEAKER_01: Right.
44:48
SPEAKER_01: It is a very complicated set of diseases and immense traction already has happened, but there's a lot of work to do to understand something that's so baffling because of its ability to evolve so quickly.
45:02
SPEAKER_00: So, so we, you know, we've both we've touched on there, these domains that we know can give us agency.
45:10
SPEAKER_00: We know if if I'm to, through whichever medium we choose, optimize for my nutrition and my sleep and my stress management and human connection and um metabolic health, all the things we always talk about that feel relatively unsexy, but when we approach them with consistency and adherence, they give us a super high ROI.
45:29
SPEAKER_00: Can we talk for a minute about things that um can help us diagnose before we have to experience that?
45:37
SPEAKER_00: And then um the precision of those tools, and then if they apply to everyone every time.
45:43
SPEAKER_00: And the example that that springs to mind is preventative MRIs, which have been become incredibly popular as of late.
45:50
unknown: Yeah.
45:51
SPEAKER_00: Um and I know they are, they have their pros and cons.
45:54
SPEAKER_00: Maybe that's worth unpacking.
45:56
SPEAKER_01: I th I think it is.
45:58
SPEAKER_01: Uh let's talk blood and MRI because they're both, but actually, first, let's start with the traditional screening tools.
46:07
SPEAKER_00: Yeah.
46:07
SPEAKER_00: Right?
46:08
SPEAKER_00: Getting ahead of myself, Paul.
46:09
SPEAKER_01: No, no, but you're right, right.
46:11
SPEAKER_01: Most people will have access, or many people will have access to some of the traditional screening tools.
46:17
SPEAKER_01: I mean, they're reasonably tried and true.
46:20
SPEAKER_01: Perfect.
46:21
SPEAKER_01: Of course not.
46:22
SPEAKER_01: I mean, PSA is a quagmire, but okay, many of these like colonoscopies and things like that.
46:29
SPEAKER_01: Yeah, you you should do them, right?
46:32
SPEAKER_01: You should do them because they catch cancers earlier.
46:35
SPEAKER_01: Um, yeah, uh, you know, these things matter.
46:39
SPEAKER_01: Um, pap smears, things like that.
46:41
SPEAKER_01: These things matter.
46:42
SPEAKER_01: Uh but then the real question would be could you find ways to catch cancer earlier when the person wasn't sick?
46:52
SPEAKER_01: Just upstream of upstream, because the idea would be hey, you know, everybody might get cancer in their life.
47:01
SPEAKER_01: Um, you'd like to catch it before they got sick.
47:04
SPEAKER_01: So you could say, okay, you could take high-risk people and you could screen like, for example, people who have Barit's esophagus, they'll get routine endoscopies.
47:13
SPEAKER_01: You know, many of us undergo routine screening that wouldn't be normal because we think we're at a risk.
47:19
SPEAKER_01: Like, for example, I get frequent endoscopies every, you know, one or two years because my dad died of stomach cancer and I don't want to have the same fate, right?
47:26
SPEAKER_01: Um, there are tools like that.
47:28
SPEAKER_01: But technology has advanced so quickly that the idea would be, you know, the blood is a reservoir, right?
47:38
SPEAKER_01: And there's data that genetic information, DNA and RNA, but especially DNA, can leach out of cancer cells and go into the blood.
47:47
SPEAKER_01: And because the blood is a repository, maybe from almost anywhere in the body, if there was an early cancer, you would be able to detect it.
47:56
SPEAKER_01: Um, and then there's increasing tools that are either sequencing-based or look at patterns of methylation of the DNA just for the lay audience.
48:07
SPEAKER_01: The DNA itself can also be modified by things called addition of methyl groups.
48:14
SPEAKER_01: And those things change how genes are expressed.
48:17
SPEAKER_01: But they can create patterns that nobody really understands, except that some of those patterns can look diagnostic for cancers.
48:27
SPEAKER_01: Um, and so you could use AI-based tools or computational tools to say, here you have this DNA that you can pull out from the blood, you don't know where it comes from, you don't even know what it is, but it has a methylation signature that makes you think that it is from a from a cancer.
48:46
SPEAKER_01: And the hope then is could you get tests like that as one example?
48:49
SPEAKER_01: Or you look for specific mutations that you think a person was at risk for and use that to screen early for cancers.
48:57
SPEAKER_01: And where I would put that at the moment is there are interesting signs, but the current level is not quite there.
49:05
SPEAKER_02: Yeah.
49:05
SPEAKER_01: Right.
49:06
SPEAKER_01: So they need to keep working on them.
49:08
SPEAKER_01: And the real risk, right, is if you get one of those tests, it doesn't a person would normally get those tests maybe for two reasons.
49:17
SPEAKER_01: One would be um because they they just want to know because they can, you know, and they'd like to catch it early.
49:25
SPEAKER_01: The other is, and the more deep reason is they're gonna go, I don't have to worry about it.
49:29
SPEAKER_01: The problem is at the current state of the test, you can't say, it doesn't give you a it doesn't give you a I don't have to, you know.
49:38
SPEAKER_01: So at the moment, it's like, uh no, you still need to do your regular stuff, right?
49:44
SPEAKER_01: Will those tests ever get to the point where it's we might be able to say, yeah, this this can be your screening tool?
49:52
SPEAKER_01: I sure hope so.
49:53
SPEAKER_01: Yeah.
49:53
SPEAKER_01: Let's we'll find out.
49:54
SPEAKER_01: You know, technology is impressive.
49:56
SPEAKER_01: Give it time, we'll see.
49:58
SPEAKER_01: Is it there now?
49:59
SPEAKER_01: No, right?
50:00
SPEAKER_01: Give it time, we'll see.
50:02
SPEAKER_01: Um the second kind of test is these MRIs.
50:07
SPEAKER_01: Um, and here's the idea like, boy, if you could just look at everything in your body and you'd catch anything that looks funky, you can you can stop anything.
50:18
SPEAKER_01: And lots of people have had this idea before.
50:21
SPEAKER_01: And MRI, hey, you're not gonna hurt anybody in doing it.
50:24
SPEAKER_01: Oh, it'll be great.
50:26
SPEAKER_01: But it's such a mixed bag.
50:28
SPEAKER_01: There are some people, in my view, okay, this is just my personal opinion, some people are such big fans of it because, hey, hey, look, they'll give you stories of people who found an early cancer and it saved their lives.
50:42
SPEAKER_01: The real problem is that nobody really knows.
50:46
SPEAKER_01: And here are the risks.
50:47
SPEAKER_01: You always have to balance the the risks.
50:50
SPEAKER_01: So when you look inside anybody's body with these tools, it's not infrequent to find something that's different or odd or problematic, right?
51:03
SPEAKER_01: And the state of the art for many of these things is that we don't actually know.
51:09
SPEAKER_01: I'll give another example, right?
51:10
SPEAKER_01: One of the things that most people are really afraid of is pancreatic cancer.
51:15
SPEAKER_01: Right.
51:16
SPEAKER_01: And so people can actually look and they used to find these um these uh kind of cystic lesions in the pancreas.
51:23
SPEAKER_01: And in those days, in the older days, they would actually do a whipple procedure where it would take out the pancreas.
51:28
SPEAKER_01: And I mean, and a lot of people died in the operating table to do this, right?
51:33
SPEAKER_01: But then you could say, Well, those who lived, you're not gonna get cancer.
51:37
SPEAKER_01: We took everything out.
51:38
SPEAKER_01: But the problem is increasing knowledge seems to say, well, most of those people would, it was just like a nodule that came and went.
51:45
SPEAKER_01: Yeah, right.
51:46
SPEAKER_01: Yeah.
51:46
SPEAKER_01: Came and went.
51:47
SPEAKER_01: So the problem is the ability to discriminate right now between a nodule that comes and goes or real cancer.
51:55
SPEAKER_01: And then you start down a path, right?
51:57
SPEAKER_00: Because you see, that would be a a false positive.
52:01
SPEAKER_01: Right.
52:01
SPEAKER_00: Is that the right?
52:02
SPEAKER_01: But it's well, it's almost it's hard to exactly call it because maybe it's maybe it's a real lesion, but it's not a lesion that would have ever cost you problems.
52:11
SPEAKER_00: But so so the the challenges you wouldn't know.
52:13
SPEAKER_00: You wouldn't know.
52:14
SPEAKER_00: You wouldn't I guess if you did them frequently over time, you might that's right.
52:18
SPEAKER_01: Right.
52:18
SPEAKER_01: So you might say, Oh, I want to watch that, but that's not what people do.
52:21
SPEAKER_00: Yeah, right.
52:22
SPEAKER_00: Yeah, yeah.
52:23
SPEAKER_01: And then and then, you know, because it'd be really hard to sit with, you know.
52:27
SPEAKER_00: And then of course, right?
52:30
SPEAKER_00: Right.
52:30
SPEAKER_01: And then and then, you know, on top of it, uh, there's no free lunches.
52:36
SPEAKER_01: You want to go in and examine something, you can make somebody very sick, right?
52:41
SPEAKER_01: I mean, my daughter, who is an internal medicine resident in Stanford, was describing, you know, telling me that she's seen cases of, you know, they go in and they put a needle, and now the person is in the ICU because they've had a bleed.
52:53
SPEAKER_01: You know, these things happen.
52:55
SPEAKER_01: So my feeling is as it sits right now, I wouldn't advocate it.
53:01
SPEAKER_01: Yeah, right.
53:01
SPEAKER_01: I mean, so where do we have a this about agency?
53:04
SPEAKER_01: Isn't it?
53:05
SPEAKER_01: It comes back to agency.
53:06
SPEAKER_01: So one thing you'd say is, well, I just want to investigate everything and go, whoo, that's not me.
53:12
SPEAKER_01: I think your much better agency is to get to the gym, to eat well, to sleep, to have social contacts.
53:17
SPEAKER_01: That's where you have real agency at the moment.
53:20
SPEAKER_00: Okay.
53:21
SPEAKER_00: Okay.
53:21
SPEAKER_00: Let's let's just double click on this for a minute because I know you.
53:25
SPEAKER_00: Um, I know you outside of this setting.
53:28
SPEAKER_00: And, you know, I don't think there are many people better positioned in the world to say that.
53:34
SPEAKER_00: Yeah.
53:34
SPEAKER_00: Right.
53:34
SPEAKER_00: That, you know, you've got agency.
53:36
SPEAKER_00: We know about the screening, we know how catastrophic this disease is for half of the people on the planet, if not more.
53:44
SPEAKER_00: But yet you still have to balance that with living the good life, right?
53:48
SPEAKER_00: And for some people, living the good life does not mean structured exercise every day or being very careful about what they eat.
53:54
SPEAKER_00: And and so I think this very human tension between, you know, how do we really just suck every bit of joy out of life whilst putting ourselves in the strongest position to be able to keep doing that for many decades.
54:10
SPEAKER_00: And for some people, that I mean, I think for everyone it looks different, right?
54:14
SPEAKER_00: I know, but but but you know, I know, for example, that your your favorite foods aren't necessarily the ones that have the most nutrient density.
54:23
SPEAKER_00: And the same applies to me, right?
54:25
SPEAKER_00: And so I know these things, you know these things.
54:28
SPEAKER_00: How do people strike that balance?
54:30
SPEAKER_01: Uh so it's I think I want to mention my uncle Walter Michel.
54:35
SPEAKER_01: So Walter Michel was my uncle, my father's brother, and he and I were very, very close.
54:41
SPEAKER_01: After my father passed, Walter and I got very, very close and stayed close until we lost him in uh 2018.
54:50
SPEAKER_01: But he was really a father figure and a mentor and ultimately a deep, deep friend.
54:56
SPEAKER_01: And um, he wrote the book, The Marshmallow Test.
54:59
SPEAKER_01: He'd spent years studying delay of gratification.
55:02
SPEAKER_01: He did the experiment with kids where the investigator would come in with the marshmallows and the bell and he would see how long the children could wait.
55:10
SPEAKER_01: They could either, you know, if they couldn't wait, they could get a marshmallow, ring the bell and get a marshmallow, or they could wait till the investigator came back and they could get the two.
55:17
SPEAKER_00: And um there's a ton of like really adorable videos online of equivalent tests.
55:22
SPEAKER_00: Yes.
55:23
SPEAKER_00: But they use like Skittles or marshmallows or gummy bears.
55:26
SPEAKER_00: Is it is adorable.
55:27
SPEAKER_00: You should people should watch that.
55:28
SPEAKER_01: And what I just loved so much about my uncle is he really believed you are neither the prisoner of your biology or your biography.
55:38
SPEAKER_01: And he, after these findings, people wanted to use it as a diagnostic test, usually of their own children, you know.
55:45
SPEAKER_01: And what Walter wanted to say was no, this is not a diagnostic test.
55:50
SPEAKER_01: This shows you where you need to build skills.
55:54
SPEAKER_01: And he spent the rest of his professional life teaching how do you learn how to wait, right?
56:01
SPEAKER_01: When you and one of his messages, you don't always want to wait.
56:04
SPEAKER_01: Yeah.
56:05
SPEAKER_01: Sometimes maybe you do want to have a second marshmallow, but for many things, how do you wait?
56:10
SPEAKER_01: So he was a smoker, right?
56:12
SPEAKER_01: You know, in the 60s, and he wanted to give up.
56:15
SPEAKER_01: So what he did was he was he walked in the hospital once and he saw a guy with a tracheostomy.
56:20
SPEAKER_01: And every time he got the desire for a cigarette, he'd visualize the guy with the with the tracheostomy.
56:27
SPEAKER_01: What he did was his concept was switching the hot with the cool, the, you know, the hot, the appetitive things that you feel the need for right away versus the cool cerebral way of thinking about it.
56:40
SPEAKER_01: Cool down certain things, right?
56:43
SPEAKER_01: And uh that extra drink, that piece of chocolate cake.
56:46
SPEAKER_01: He he got celiac disease.
56:48
SPEAKER_01: So all of a sudden in his mind, he starts seeing chocolate cake as a, you know, as something disgusting and villainous.
56:54
SPEAKER_01: So part of the question is how can a person live their life so that they cultivate the habits that be the things that are actually good for you?
57:02
SPEAKER_01: I mean, if you think about the inherent feelings of eating well, socializing, exercising, they feel really good.
57:13
SPEAKER_01: And I think it's more about people getting back in touch with those people don't have to run a marathon.
57:21
SPEAKER_01: Going for a walk, you know.
57:23
SPEAKER_01: I mean, literally the concepts behind it they're getting back in touch with things that are incredibly natural for human beings.
57:34
SPEAKER_01: We're evolved to be that way.
57:36
SPEAKER_01: It's coming back to our most natural basic habits.
57:39
SPEAKER_00: To socialize, to be part of a group, to eat well.
57:42
SPEAKER_01: If food looks delicious to you, very often the you know, fake food is made to look delicious to you and to circumvent your thinking.
57:53
SPEAKER_01: Sure.
57:53
SPEAKER_01: Real food, when you really look at it, is very delicious and appetitive and wonderful.
57:59
SPEAKER_00: Yeah, that we had uh Dariush Mozafarian on last week as well, and he says exactly the same thing that we've been misled to believe that that is the thing that is tasty and a treat when really it's not not the case.
58:10
SPEAKER_00: I wonder if we've, you know, um, it's not, you know, it's not a zero-sum game.
58:15
SPEAKER_00: Like to do something that's good for you doesn't mean delaying gratification, really.
58:19
SPEAKER_00: You know, I think when we think about the process um certainly of how we improve our brain chemistry when we do work out, not just when we're working out, but that when you finish that that complex cocktail of hormones in our brain, we can improve that intentionally.
58:36
SPEAKER_00: I mean, yeah.
58:37
SPEAKER_01: I I love what you said because it's really about actually coming to feel that the things that are good for you are actually a reward.
58:46
SPEAKER_00: Yeah.
58:47
SPEAKER_01: Like I love those things.
58:48
SPEAKER_01: They feel good to me, you know.
58:51
SPEAKER_00: We should feel lucky to work out in the morning.
58:54
SPEAKER_01: Oh.
58:54
SPEAKER_00: Do you work out in the morning?
58:56
SPEAKER_01: I work out on the weekends in the morning, on the weekdays in the afternoons.
59:00
SPEAKER_01: So I I've been uh I'm a big exerciser between I use the tonal to build muscle, I do uh infraresistance training, I do high-intensity interval training, I do yoga, I do spin class, and I walk a lot with my dogs.
59:14
SPEAKER_01: And for me, it's very social.
59:16
SPEAKER_01: I do it with my wife and my daughters and their partners, and yeah, it's very social.
59:21
SPEAKER_00: Have you always been into exercise?
59:22
SPEAKER_00: Have you always had these um, you know, uh positive health habits?
59:27
SPEAKER_01: Yeah.
59:28
SPEAKER_00: Or has that changed as you have learned more about what you do?
59:31
SPEAKER_01: Oh, it's it's it's changed.
59:32
SPEAKER_01: So I mean, I hope you don't mind a sort of ridiculous story.
59:36
SPEAKER_01: But my father was a European intellectual, and he thought exercising was something that you did if you weren't smart.
59:45
SPEAKER_01: He really, you know, you're like, you don't you use your brain, you don't use your body.
59:51
SPEAKER_01: And so consequently, you know, my brother and I grew up in upstate New York were these two smaller boys who got beaten up.
59:59
SPEAKER_01: And we, through my maternal uncle, Charles, taught my brother and I how to box.
1:00:06
SPEAKER_01: And so we stopped getting picked on, but I began to realize that the social currency was sports.
1:00:11
SPEAKER_01: So my brother and I started playing sports, and then I started realizing how much I liked that.
1:00:17
SPEAKER_01: And my brother and I would always, we were little guys, so we were always trying to get stronger.
1:00:22
SPEAKER_01: But I think what's happened over the last few years, I've just been upping it and upping it and upping it.
1:00:27
SPEAKER_01: And, you know, particularly now, I'm 63, I am so focused on building muscle because I'd like to have that suit of armor going forward.
1:00:37
SPEAKER_00: Yeah.
1:00:37
SPEAKER_00: Yeah, that really is the currency of longevity.
1:00:40
SPEAKER_00: The more we the more we research, the more we find out about um, you know, optimizing for body composition.
1:00:46
SPEAKER_00: Yeah.
1:00:46
SPEAKER_00: And then we often talk about this, you know, thinking about everyone in your life who's made it to their 90s and beyond, you know, very rarely are they running around a football pitch with their grandchildren on their shoulders.
1:00:57
SPEAKER_00: That that immobility, fragility, and codependence is pretty almost across that entirety of the group.
1:01:03
SPEAKER_00: And given that we know how to build those things, that's the thing I think we should be approaching with urgency.
1:01:09
SPEAKER_00: Do you think that that same thing applies?
1:01:11
SPEAKER_00: You know, this we often use the analogy of a good financial investment.
1:01:15
SPEAKER_00: You know, if you start saving for a pension in your 20s, then it's a lot less friction and it's a lot less painful to then have this abundance of wealth in your, you know, 60s and beyond.
1:01:26
SPEAKER_00: Yeah.
1:01:27
SPEAKER_00: Do you think the same thing applies um on a biological level for the prevention of onset of these cancers, given that age is probably the biggest risk factor for most of them?
1:01:36
unknown: Right.
1:01:37
SPEAKER_01: Maybe both yes and no.
1:01:39
SPEAKER_01: Oh, so you know, on the yes idea, that probably the earlier you start, the easier it is to build muscle, the more you get in the habit of exercise, the more you tune your metabolism, the healthier you are.
1:01:53
SPEAKER_01: But I think the interesting part of the message is that it's actually never too late to start.
1:01:59
SPEAKER_01: I mean, it's really interesting.
1:02:00
SPEAKER_01: My wife Deborah has told me these studies about doing high-intensity interval training and people who are practically wheelchair bound and how all of a sudden they're building muscle, you know.
1:02:10
SPEAKER_01: So what's remarkable is that the benefits probably link to those, I don't think it's been as rigorously studied, but the health benefits in terms of cancer risk prevention probably go to those individuals as well.
1:02:22
SPEAKER_01: So the message is start early if you can.
1:02:26
SPEAKER_01: But if you haven't started early, it's fine.
1:02:29
SPEAKER_01: Just start.
1:02:30
SPEAKER_00: Yeah.
1:02:30
SPEAKER_00: Well, I think with this idea that, and I really I'm gonna unpack this with Deb tomorrow, but the idea that, you know, we should be associating a certain chronological age with frailty and weakness and just being old in general is a bit of a misnomer because we we know how to not necessarily prevent that, but certainly slow that decline down and improve the met those metrics across the board.
1:02:53
SPEAKER_00: You know, certainly with lean tissue mass, metabolic health, cognition, cognition markers, mobility, endurance, heart and lung function.
1:03:01
SPEAKER_00: Like we see that every day.
1:03:02
SPEAKER_00: And so I think that is the big takeaway, I think, for everyone who is in their, you know, latter years is like, don't let that be the defining factor because that you have a ton of agency still.
1:03:14
SPEAKER_01: That's right.
1:03:14
SPEAKER_01: I mean, I even think too, since we started interacting, I'm much stronger, right?
1:03:20
SPEAKER_01: Now that's not supposed to happen to people in their 60s.
1:03:23
SPEAKER_01: It's happening to me, right?
1:03:25
SPEAKER_01: And it's because you can do things, right?
1:03:27
SPEAKER_01: That's agency.
1:03:28
SPEAKER_00: Yeah.
1:03:29
SPEAKER_00: And I think that that I love that analogy of building a suit of armor because we can put on that suit of armor whenever.
1:03:36
SPEAKER_01: Yeah.
1:03:37
SPEAKER_00: We just have to dedicate the sort of time and energy to it.
1:03:40
SPEAKER_00: But I think this is is kind of um a message that gets a bit lost in the misinformation and grandiose claims in general across health.
1:03:51
SPEAKER_00: And and so, you know, I think if we are to take your specific domain, I've heard so many conflicting perspectives on cancer diagnosis and treatment and management and therapy in general.
1:04:04
SPEAKER_00: Would you say there are, you know, one or two myths, pieces of misinformation that you would like to uh remove entirely?
1:04:14
SPEAKER_01: Well, if I'm gonna be honest, to me, the most disturbing risk, the most disturbing myth is one that's never specifically stated, but which has an undercurrent, which is if you get cancer, it's your fault.
1:04:27
SPEAKER_01: It really bothers me because okay, what if somebody didn't have the best habits?
1:04:33
SPEAKER_01: What if they didn't eat well?
1:04:35
SPEAKER_01: What if they didn't exercise?
1:04:37
SPEAKER_01: Is it really their fault?
1:04:38
SPEAKER_01: Right?
1:04:39
SPEAKER_01: They didn't do it deliberately, they're suffering the consequences.
1:04:42
SPEAKER_01: It's a it's a completely uncompassionate, unfair way to view it.
1:04:48
SPEAKER_01: And I think it's actually very prevalent um amongst people, particularly on social media.
1:04:54
SPEAKER_01: Yeah.
1:04:54
SPEAKER_01: It feels really wrong to me.
1:04:56
SPEAKER_01: That's a myth that just gets under the skin.
1:04:59
SPEAKER_00: Um I think on the flip side of that as well, that that you could do everything right.
1:05:03
SPEAKER_01: That's right.
1:05:04
SPEAKER_00: And you have no guarantee.
1:05:06
SPEAKER_01: That's right.
1:05:07
SPEAKER_01: That's right.
1:05:08
SPEAKER_00: That's right.
1:05:08
SPEAKER_00: The more I've spent working in this space as well, the more this this sort of socioeconomic divide is is troublesome, is bothering because you know, it's easy to say to people eat a ton of fruit and vegetables every day and work out and do all this kind of strength training, go to these gyms and like get these different therapies and treatments, and then you're uh, you know, a single dad with two kids trying to make ends meet and working two jobs, and it is not cheap to do everything right.
1:05:40
SPEAKER_00: And so I think that's even with the best intentions, you could be trying to do the things that are helping prevent this illness.
1:05:46
SPEAKER_01: Right.
1:05:47
SPEAKER_01: I mean, I'll give an example, right?
1:05:48
SPEAKER_01: We had wood floors need to be redone because there was a water accident, right?
1:05:52
SPEAKER_01: And so they had to sand the floors and then they had and actually uh put in new planks and sand the floors and then stain them.
1:06:00
SPEAKER_01: And the exposure to me smelled so toxic.
1:06:04
SPEAKER_01: I didn't even want to be in the house, certainly not sleep there.
1:06:07
SPEAKER_01: And I'm thinking, these poor guys are exposed to this every day.
1:06:12
SPEAKER_01: I mean, there are people who do these jobs that have that incur tremendous exposures that we forget about, you know, and we shouldn't forget about them.
1:06:21
SPEAKER_00: Yeah.
1:06:24
SPEAKER_00: So, Paul, can I ask you a couple of personal questions?
1:06:29
SPEAKER_01: Yeah, of course.
1:06:30
SPEAKER_00: Um, and you can take as long or as little time as you want to answer these, and we can cut any of them out.
1:06:36
SPEAKER_00: Um, so what is one thing that you wish you had known 20 years ago today?
1:06:43
SPEAKER_01: Well, I'll be very personal.
1:06:46
SPEAKER_01: I think 20 years ago, I you know, after my dad died and he left us uh uninsured, I felt small and insignificant.
1:06:59
SPEAKER_01: And I wanted to have people say, you matter, right?
1:07:05
SPEAKER_01: And I think I cared so much about that that I wanted people to look at the signs that I did and say, hey, it matters.
1:07:16
SPEAKER_01: And I think my science changed when I said, I've just got my own voice.
1:07:22
SPEAKER_01: And I think I wish I had given that to myself earlier, but maybe it just doesn't matter because maybe I wasn't ready for it.
1:07:30
SPEAKER_01: But that's what I think.
1:07:32
SPEAKER_00: I wonder if everyone thinks that.
1:07:33
SPEAKER_00: I mean, I certainly did.
1:07:34
SPEAKER_01: You did?
1:07:35
SPEAKER_00: Well, I wonder if that is a thing that just becomes with you know, this with age, like youth is wasted on the young, right?
1:07:40
SPEAKER_00: And I think as we yeah as we get older and understand our self-worth and self-value, maybe that's just the price we pay for for being younger.
1:07:50
SPEAKER_01: But it but it's interesting that we're having this conversation because what it calls to mind for me is how hard it is to be vulnerable and how powerful it is to be vulnerable, you know.
1:08:03
SPEAKER_01: And God, I wish I'd known that 20 years ago.
1:08:05
SPEAKER_00: Yeah.
1:08:06
SPEAKER_00: And just that that is part of the human condition.
1:08:08
SPEAKER_01: That's part of the human condition.
1:08:10
SPEAKER_00: And we all experience that.
1:08:11
SPEAKER_00: Yeah.
1:08:11
SPEAKER_00: And it doesn't matter who you are, like everyone is going through some of these same challenges and troubles.
1:08:17
SPEAKER_00: And it'd be better if we all spoke about it more, I'm sure.
1:08:20
SPEAKER_01: And how remarkably kind other people are when they see it.
1:08:24
SPEAKER_01: There are, of course, a few who will try to exploit you, but that's not most of humanity.
1:08:28
SPEAKER_01: Most people will connect to it.
1:08:30
SPEAKER_00: Yeah.
1:08:31
SPEAKER_00: If you had any amount of funding, you've got an unlimited part of funding, unlimited resources, support, the tools and technologies.
1:08:40
SPEAKER_00: What one question within your field would you like to answer?
1:08:46
SPEAKER_00: So, what would you like to study?
1:08:47
SPEAKER_00: What would you like to solve that hasn't yet been solved?
1:08:51
SPEAKER_01: How do you develop more effective treatments for people whose cancers have extra chromosomal DNA?
1:08:59
SPEAKER_01: Um I know the people, I know the team, we know how to work together.
1:09:05
SPEAKER_01: To me, that's priority number one, because that probably affects close to four million people a year.
1:09:12
SPEAKER_01: And people whose cancers have extra chromosomal DNA do worse than all other cancer patients.
1:09:19
SPEAKER_01: Four million people a year, that's an estimate.
1:09:21
SPEAKER_01: Yep.
1:09:21
SPEAKER_00: But how much do you think that would how much funding do you think that would need?
1:09:28
SPEAKER_01: It depends on how fast we want it to go.
1:09:31
SPEAKER_01: Um and there's multiple phases of it, right?
1:09:34
SPEAKER_01: I mean, one phase of it is the testing of early phase ideas.
1:09:41
SPEAKER_01: The second is to get it to new drug development into the clinic and testing.
1:09:48
SPEAKER_01: The latter parts are phenomenally expensive and time consuming.
1:09:53
SPEAKER_00: And time consuming.
1:09:54
SPEAKER_00: Do you do you think that this evolution of AI will help?
1:09:58
SPEAKER_00: Um I'm certain it was already helping, but will it help to speed up that process of taking these things from bench to bedside?
1:10:06
SPEAKER_01: I've been thinking about this a lot.
1:10:08
SPEAKER_01: Um you know, my brother said something interesting to me.
1:10:12
SPEAKER_01: He's been diving into this.
1:10:13
SPEAKER_01: And he said, you know, if you're using AI, you're doing the wrong thing.
1:10:16
SPEAKER_01: You should be collaborating with AI, which I think is a wise way of thinking about this.
1:10:21
SPEAKER_01: Um where I think it's poised to make it.
1:10:26
SPEAKER_02: What does that mean?
1:10:27
SPEAKER_01: So if you use AI as your oracle, you're just like getting the lowest grade that you could, right?
1:10:35
SPEAKER_01: If you're actually using AI to poke holes in your thinking, yeah, yeah, right, and then interacting with it on that front, it gets much more interesting.
1:10:43
SPEAKER_02: Yeah.
1:10:43
SPEAKER_01: But that's just one aspect of it.
1:10:45
SPEAKER_01: I think it's going to make a big difference in diagnostics, you know, and it's going to be needed because there won't be enough pathologists or radiologists to read out all the scans or biopsies or clinical tests, you know, for the aging population.
1:10:59
SPEAKER_01: But I think the other place where it's poised to make a big difference, where I I think about it this a lot because we have work that goes from academia to to biotech, is in drug development.
1:11:10
SPEAKER_01: Now, and when when drug development is interesting because we think about proteins and we normally think about the sequence of the proteins that comes from the sequence of the RNA, that comes from the sequence of DNA, but nature speaks in shapes, right?
1:11:23
SPEAKER_01: And it doesn't speak in letters, it's shapes, right?
1:11:26
SPEAKER_01: And so drugs typically have to find or bind pockets inside proteins.
1:11:32
SPEAKER_01: And there's brilliant chemists like the one I work with closely with Ben Cravat at the Scripps Institute, who really is developing incredible tools for this.
1:11:39
SPEAKER_01: But AI is a way where you could actually use these tools to help refine.
1:11:44
SPEAKER_01: You see compounds that have this structure do this to this protein.
1:11:48
SPEAKER_01: But if you have enough of them, it can start seeing patterns that can enlighten you.
1:11:53
SPEAKER_01: And there's a, you know, a number of really, I think, very forward-thinking companies that are already using these approaches.
1:11:58
SPEAKER_01: I suspect that that is going to have a money and time-saving impact of the valve.
1:12:06
SPEAKER_00: Some of that is a math problem, right?
1:12:07
SPEAKER_00: There's so many different secrets.
1:12:09
SPEAKER_00: That's right.
1:12:09
SPEAKER_00: That's right.
1:12:10
SPEAKER_01: That's right.
1:12:10
SPEAKER_01: And, you know, and it goes even beyond math because it'll be patterns that you wouldn't even expect.
1:12:17
SPEAKER_01: Because once you actually get to the math problem to tell you what to look at, it enlightens you on potentially on what you saw about the structure that might be useful.
1:12:28
SPEAKER_01: That I think is going to prove to be very useful.
1:12:31
SPEAKER_00: Are you optimistic in general about the next 10 years?
1:12:34
SPEAKER_01: Sounds like yes, but are we talking about cancer research or life?
1:12:38
SPEAKER_01: Or I just want to make sure that I'm I'm optimistic about the research.
1:12:42
SPEAKER_00: I'd like cancer research first and then life second.
1:12:44
SPEAKER_01: Uh yeah.
1:12:45
SPEAKER_01: Cancer research, yeah.
1:12:47
SPEAKER_01: I don't think you can stop science.
1:12:49
SPEAKER_01: I'm very disturbed by what's happening in the United States, deeply disturbed.
1:12:54
SPEAKER_01: Um, but I think you can't stop science.
1:12:57
SPEAKER_01: Uh, and I think that's very important.
1:12:59
SPEAKER_01: And this has to be global and it has to be partnership.
1:13:03
SPEAKER_01: Um, and so at least I'm finding ways to do that.
1:13:07
SPEAKER_01: Um, I hope many others will too, because that's actually how we're going to make progress going forward.
1:13:13
SPEAKER_01: Cancer research is not a national good.
1:13:15
SPEAKER_01: You know, cancer research belongs to everybody, you know, and matters to everybody.
1:13:20
SPEAKER_01: So am I optimistic?
1:13:21
SPEAKER_01: I am so optimistic about the science.
1:13:23
SPEAKER_01: I wish we weren't dealing with these headwinds, but I am very optimistic about science and what science can actually do for humanity.
1:13:33
SPEAKER_01: The evidence is just it's it couldn't be clearer, right?
1:13:37
SPEAKER_01: And people, there are so many brilliant people.
1:13:40
SPEAKER_01: We'll find our way here, particularly if we work together.
1:13:43
SPEAKER_01: Am I optimistic about life?
1:13:44
SPEAKER_01: Yeah.
1:13:45
SPEAKER_01: Again, I'm saddened by things that I see around me.
1:13:49
SPEAKER_01: You know, it it's it's painful to watch the kind of cruelty and hurt and sadness, you know, around us.
1:13:57
SPEAKER_01: Um, but I am optimistic about the human condition.
1:14:01
SPEAKER_01: I'm certainly optimistic about my own life because I'm surrounded by people who I love so much, right?
1:14:06
SPEAKER_01: Uh, and because I do work that means so much to me.
1:14:10
SPEAKER_01: Um uh and I'm amazed by the resilience of the human spirit.
1:14:16
SPEAKER_01: Um so the answer is yes, I am.
1:14:19
SPEAKER_01: I hope that that times will become easier and kinder and gentler, but yes, I am optimistic about that too.
1:14:27
SPEAKER_00: Uh you know, being talking from your clinician perspective now, have you observed a noticeable difference in the outcome for those that share that perspective?
1:14:40
SPEAKER_00: People that live with this glass half full, optimistic, positive mindset relative to others?
1:14:47
SPEAKER_00: Because I've heard some remarkable stories.
1:14:49
SPEAKER_00: Yeah.
1:14:49
SPEAKER_01: I I think the answer is yes.
1:14:51
SPEAKER_01: You know, um, so one of the cancers that I've had a long-standing interest in is this glioblastoma brain cancer.
1:14:58
SPEAKER_01: And when people are diagnosed with it, they look at the statistics and they're just horrified.
1:15:04
SPEAKER_01: And I've had a lot of people call me not as their doctor, but as somebody who has knowledge base in the field, you know, say, what do you what do you think?
1:15:14
SPEAKER_01: And what I tell them about was the story of Stephen Jay Gould, the evolutionary biologist at Harvard.
1:15:20
SPEAKER_01: So Stephen Jay Gould was diagnosed with a mesothelioma, which is like the cancer that it's probably even worse prognosis than glioblastoma.
1:15:31
SPEAKER_01: And what he did is being a scientist, he dived into it.
1:15:34
SPEAKER_01: And people normally normally report medians, right?
1:15:39
SPEAKER_01: So the median survival is six months or five months or nine months.
1:15:44
SPEAKER_01: So he began to look carefully as a scientist at this.
1:15:47
SPEAKER_01: And what he noticed is yes, you've got a median, but you've got a long tail.
1:15:51
SPEAKER_01: And so there's some people out there who are living five, 10, 15 years.
1:15:56
SPEAKER_01: So he wrote a very influential paper called The Median is not the message, you know, based upon the me, you know, uh, medium is not the message.
1:16:04
SPEAKER_01: Um, and and it's a very important point, which is if somebody's diagnosed with something, they should see that.
1:16:12
SPEAKER_01: So I'm going to be that person on the right side of the code.
1:16:16
SPEAKER_00: So just to be super clear here, you mean that, yeah, sure, there are a big percentage of the people that get this diagnosis don't survive for a long time, but there are a bunch that do.
1:16:26
SPEAKER_01: Yeah.
1:16:26
SPEAKER_00: And so why not me?
1:16:27
SPEAKER_01: Exactly.
1:16:28
SPEAKER_01: And even more, what do I need to do for that to be me?
1:16:32
SPEAKER_00: Yeah.
1:16:33
SPEAKER_01: And what's fascinating is there already are some data on that.
1:16:37
SPEAKER_00: Tell me.
1:16:38
SPEAKER_01: I mean, aside from being treated appropriately, yeah.
1:16:41
SPEAKER_01: Um, and social connectivity exercise, Dina says, that moves you to the right side of the curve.
1:16:47
SPEAKER_00: So once being once they have been diagnosed, then you know, it becoming even more important to do the things that we know the matter.
1:16:55
SPEAKER_01: That's right.
1:16:56
SPEAKER_00: Paul, I could speak to you for hours.
1:16:58
SPEAKER_00: Um, we probably have already, but let me ask you a couple of questions to finish, and then I'll let you go.
1:17:04
SPEAKER_00: Um, if you weren't a scientist, what do you think you'd be doing?
1:17:09
SPEAKER_01: You know, it's funny.
1:17:10
SPEAKER_01: I asked myself that recently.
1:17:13
SPEAKER_01: The truth is, I can't imagine myself not being a scientist.
1:17:17
SPEAKER_01: And I'll tell you why.
1:17:18
SPEAKER_01: My father had a library, he was a real scholar, he had a library of like 3,000 books.
1:17:24
SPEAKER_01: And my favorite place to be in the entire world was in my father's study with my father, with all of these books on the shelves.
1:17:32
SPEAKER_01: And the ones that I always gravitated to were the science books.
1:17:35
SPEAKER_01: I think it's just in me.
1:17:37
SPEAKER_00: Yeah.
1:17:37
SPEAKER_01: Yeah.
1:17:39
SPEAKER_00: Fate.
1:17:40
SPEAKER_01: Fate and choice.
1:17:43
SPEAKER_00: Agency.
1:17:44
SPEAKER_01: Yeah.
1:17:44
SPEAKER_00: What's your favorite book of all time?
1:17:48
SPEAKER_01: Can I give you a few?
1:17:50
SPEAKER_00: Sure.
1:17:51
SPEAKER_01: Okay.
1:17:51
SPEAKER_01: One of them is a book that I read recently that still stuns me.
1:17:55
SPEAKER_01: It's a book called Stoner by John Williams.
1:17:58
SPEAKER_01: It's a book that nobody had heard of.
1:18:01
SPEAKER_01: Stoner S-T-O-N-A-R.
1:18:02
SPEAKER_01: That's the name of the character.
1:18:04
SPEAKER_01: And it's about scholarship.
1:18:06
SPEAKER_01: And it is such an incredibly beautiful, beautiful, beautiful book.
1:18:12
SPEAKER_01: Um Fiction.
1:18:13
SPEAKER_01: Fiction.
1:18:14
SPEAKER_01: It's a stunning book, deeply meaningful.
1:18:18
SPEAKER_01: Deborah's read it.
1:18:19
SPEAKER_01: My daughters have read it.
1:18:21
SPEAKER_01: All of us are just you gotta read it.
1:18:23
SPEAKER_01: It's gonna read it.
1:18:24
SPEAKER_01: It is a brilliant and extremely moving and beautiful, beautiful, beautiful book.
1:18:30
SPEAKER_01: Um that one meant a lot to me.
1:18:34
SPEAKER_01: Um James Joyce's Ulysses was a very important book for me, and I couldn't even tell you why.
1:18:41
SPEAKER_01: Um uh and the Iliad and the Odyssey meant a lot to me.
1:18:46
SPEAKER_01: I I couldn't even tell you why.
1:18:47
SPEAKER_01: Hard to put your finger on, right?
1:18:48
SPEAKER_01: I think.
1:18:49
SPEAKER_00: But they didn't meant a lot to me.
1:18:50
SPEAKER_01: Yeah.
1:18:51
SPEAKER_00: Have you read A Man's Search for Meaning?
1:18:53
SPEAKER_01: Yes, I have.
1:18:55
SPEAKER_01: I gave it to my father for his birthday when I was 11.
1:18:59
SPEAKER_00: Did you really?
1:19:00
SPEAKER_00: I did.
1:19:01
SPEAKER_00: I thought that was a wonderful book.
1:19:03
SPEAKER_00: Okay, so I'm gonna ask you a couple of quick fire questions to finish.
1:19:09
SPEAKER_00: Um you have less than 30 seconds to answer each.
1:19:14
SPEAKER_00: Okay.
1:19:14
SPEAKER_00: Most underrated longevity hack.
1:19:20
SPEAKER_01: Spending time with your friends.
1:19:22
SPEAKER_00: I couldn't agree more.
1:19:23
SPEAKER_00: Most overrated.
1:19:28
SPEAKER_01: Cold plunges.
1:19:30
SPEAKER_01: I agree as well.
1:19:31
SPEAKER_00: Yeah.
1:19:32
SPEAKER_00: I think the cold plunge, I think the reason why you feel so good, and don't hold me to any science here, but I can't see any great science for longevity.
1:19:39
SPEAKER_00: But I think the reason you feel so good when you get out is you're no longer doing a cold plunge.
1:19:43
SPEAKER_01: Yeah, I think that's right.
1:19:44
SPEAKER_00: Yeah.
1:19:44
SPEAKER_00: Do you uh this is a personal question, um, so we can take this out if you want.
1:19:49
SPEAKER_00: Do you what what are the top three things that you and your wife disagree about with regards to science?
1:19:58
SPEAKER_00: Not just in general.
1:20:01
SPEAKER_01: Oh gosh, we actually just had a really interesting discussion about by the way.
1:20:06
SPEAKER_00: I'm gonna ask Deborah the same thing.
1:20:08
SPEAKER_01: Yeah, no, that we actually just had a really interesting discussion about this.
1:20:12
SPEAKER_01: I wouldn't call it a disagreement, but I would call it a reshaping in a discussion about the difference between random large randomized controlled clinical trials versus small boutique studies.
1:20:26
SPEAKER_01: We're still the two of us putting our heads together around that.
1:20:30
SPEAKER_00: Can we can we finish actually on just unpacking a bit about that?
1:20:35
SPEAKER_00: Not that specifically, but I think communication messaging in science in general.
1:20:42
SPEAKER_00: Because I think this is really important.
1:20:43
SPEAKER_00: And you touched on this just before we started recording.
1:20:45
SPEAKER_00: And I think as a message to the general public, this is this is worth you know speaking about.
1:20:50
SPEAKER_00: How do we as consumers get a clearer message about what works and what doesn't?
1:20:56
SPEAKER_01: Right.
1:20:57
SPEAKER_01: This is incredibly important.
1:21:00
SPEAKER_01: Um, I think I think there's responsibilities on both ends of this of this conversation.
1:21:08
SPEAKER_01: So on one hand, I think that physicians and scientists have not in general done a good job of communicating to the intelligent public um in a way that is clear, concise, not hedged, not cloaked in complicated language, but very real and provided in the sense of um what we know and what we think as opposed to mandates you must do.
1:21:45
SPEAKER_01: Because there's a level of resistance that comes in when anybody tells you you must do this.
1:21:51
SPEAKER_01: But if somebody tells you, well, this is what we know, this is what we think, but it's your choice, people react very differently.
1:21:59
SPEAKER_00: And I think less defensive.
1:22:02
SPEAKER_00: That's right.
1:22:02
SPEAKER_01: Like, oh, wait a minute.
1:22:03
SPEAKER_01: Well, you know, I want to do well, you know.
1:22:05
SPEAKER_01: Okay, you think this is the right treatment?
1:22:07
SPEAKER_01: Okay, let me think about it, you know.
1:22:09
SPEAKER_01: Um, and but even more explaining why in academia, I think there's been a value in communicating in nuanced, hedged way.
1:22:22
SPEAKER_01: And I guess what's at the heart of it for me, Chris, is that somehow we're taught in academia to remove ourselves from the equation.
1:22:33
SPEAKER_01: Now, on one level, it's good to remove ourselves from the equation because what we should really be caring about is what's right for knowledge and other people.
1:22:42
SPEAKER_01: So we should remove ourselves and our reward desires from that.
1:22:47
SPEAKER_01: But on the other hand, when we communicate to other people, we do a disservice if we don't expose who we are as human beings and why we care about what it is that we're doing.
1:23:01
SPEAKER_01: And then I think there's a responsibility of the listener to listen, right?
1:23:07
SPEAKER_01: Yeah, hear it, listen, ask questions.
1:23:10
SPEAKER_02: Huh.
1:23:12
SPEAKER_02: That's such a great point.
1:23:16
SPEAKER_00: More questions.
1:23:18
SPEAKER_00: Paul, I could spend another four hours talking to you, but um, I'm so glad that you are part of this project.
1:23:24
SPEAKER_00: I'm so glad that you exist doing what you are doing.
1:23:27
SPEAKER_00: You're a brilliant man.
1:23:28
SPEAKER_00: Thank you.
1:23:28
SPEAKER_00: And I have so much time and respect for you.
1:23:30
SPEAKER_00: It's been a privilege and a pleasure.
1:23:31
SPEAKER_01: Thank you, Chris.
1:23:32
SPEAKER_01: And the feeling is very mutual.