The Comedy Cellar: Live from the Table - I'm Terrified of Cancer. So I Called My Childhood Friend Kenan Onel, Cancer Geneticist.

Episode Date: July 23, 2026

0:00 The friend he hasn't seen since sixth grade 5:16 Angelina Jolie, BRCA, and the 20% nobody tells women about 18:23 What a cancer cell actually is - and why tumors evolve 26:31 How cancer actually kills you, and what a seizure is 32:14 The last cigarette: why he can't take the test every week 46:27 The best medicine in the world, and who can't get to it 1:03:23 Telling a family there's nothing left Noam hadn't seen Kenan Onel since high school in Ardsley, where Onel graduated first in the class and Noam, by his own account, drifted somewhere well below. Fifty years later Onel runs genetics and genomics at Roswell Park - the only comprehensive cancer center in all of western New York - and Noam has one thing he wants to ask him about. He's afraid of cancer. His grandfather died of it. His father died of it. He's taken the Grail blood test, it came back clean, and he wants to know why he can't just take it every week. What follows is part reunion and part interrogation. Onel explains what a cancer cell actually is, why tumors evolve like finches in the Galapagos, and what is physically happening to someone during a seizure. He explains how cancer kills - the mechanism, organ by organ. And he tells Noam that the test he's counting on just failed its biggest trial in the UK, which sets off the real argument of the hour: whether a guideline written for a population means anything at all to the one person sitting in the chair. Then, near the end, Noam asks how you tell a family there's nothing left to offer. The answer is the best thing in the episode. Also: the 20% of women who are high-risk and have never been told, the doctor who warned Noam that Pellegrino was bad for his son's bones, a scan booked by 4pm the next afternoon, and one entire podcast without mentioning Israel. Dr. Kenan Onel is Chief of the Division of Genetics and Genomics and Director of the Center for Precision Oncology and Cancer Prevention at Roswell Park Comprehensive Cancer Center. Live from the Table is the official podcast of the world-famous Comedy Cellar.

Well, here's something it fascinates me. It's not to do with medicine. How do you tell somebody that it's over, you know, that they've got three months, four months? This is live from the table, the official podcast of the World Famous Comedy Cellar. We're here via Zoom. Everybody is out of studio today. This is Dan Natterman.

I'm here with Noam Gorman. He's coming to us from his summer home in Maine. And we have with us also by us. also via Zoom, Dr. Ken O'nell. He is a specialist in oncology, genetics, and genomics. We're certified in pediatric chemotherapy oncology and a clinical cancer geneticists. So welcome. All right.

So this is, okay, forget about that for a second. So how, so this is it. This is Kenan O'nell. This is a childhood friend of mine. Yes. You can know each other forever. I haven't seen a very long time. And I've sort of been following your career.

And now that I've gotten old enough to not want to get cancer. No, I've wanted to make contact with you. So let me just say, when I was, I grew up in Manhattan until the sixth grade. And then, you know, they had kind of standardized tests, I guess. And then when I moved to Ardsley, which is where Kenano and I went to school, I guess because of the margin of error, like, you know, anything can happen. I placed in to the very highest group in the sixth grade. And I don't remember, Kenan, they used to, they told us, they divided A, B, C, D.

That's right. O.P. We were in O.P. There were four of us. And we knew we were the smartest kids in the class, right? And he graduated first in the class, by the way. I drifted way lower after that. Do you remember the names of the kids in our, in our O.P?

It was Andy Zismore and Brayne. That's right. Right, me, you, and he just weren't Doug Wayne. I don't know. I'm still friends with Larry Adio. He's still friends with Joe. Oh, I was he. He's very good.

He's very good. He has, he's went into his family's bakery business. He looks fantastic. And like I think most of us, he hasn't changed. Yes, you look completely the same. I don't mean it looks, but I mean, personality-wise. And we sound the same. And we sound the same.

And then, and then, Kinnon, you know, and like I said, I margin of error, I wasn't actually being humble. And I, I was pretty smart, but he was the smartest kid, obviously, in our class. That's true. Even Mr. Clancy commented on it. And I do know one other things. So when we were early on, we had what's now called a play date. You and I, I don't know if remember this.

And I went to your house. and I'd grown up in Manhattan, like in like left wing, progressive, open corridor system. We barely had homework, you know, and ours all of a sudden was like old school at homework. And we get to your house and we're going to like play or something, right? And your mother, I remember this. This is where you were going. Oh, no, you're not.

You're going to sit down right now and do your homework. And she made us sit down. the first thing when we got home and do our homework. And let me tell you, this has had a lifelong impact on me. Your mother, that one day, it stayed with me the rest of my life. I said, ah, this is how you're supposed to raise kids. I was not raised that way. And to this day, to this day, I suffer from bad work habits because I was allowed to just skate by. And by the time that I got old enough that I couldn't just skate by. I didn't have the habits. You think it's because you think it's because you were raised? You know, you're a big fan of

genetics. No, maybe you're just, you just have bad work habits because that's who you are. It's possible. Well, what do you think? I'll call it your care. Right. It's always nature or nurture, right? Or some combination there are. It's funny, actually, because my inherent nature is to procrastinate. You know, if I can. and put something off, I will. It doesn't matter what it is, but I'll put it off. So I suppose the take a message for all of us is that we all need a mother to make us do stuff, right? Yes, yeah.

And one last thing, because it just came to my mind. I don't know why I remember this. I'm pretty sure this actually is true. Do you remember seeing the movie Serpico with Al Pacino? Sure. At the day, when it came out. Yes. Yeah, I remember that because it wasn't typical of kids' R-A.

She'd be able to go see those R-rated movies. Right. And it's a scene with her naked breast in the... Yeah, in the bathtub. Yeah, I remember you and me talking about it. Oh, my God, it's amazing what you... I can't remember anything from last week, and I remember things like... Anyway, okay.

So here we are. I'm 63. I'm going to be 64 tomorrow. Oh, my God. Congratulations. Thank you. And, you know, my grandfather died of lung cancer, smoker. My father died of lung cancer. He had been a smoker until, you know, like, let's see, until he was around 50 years old, something like that, 48.49. Then he stopped.

I am very, very scared of getting cancer. You are an expert in cancer. I've taken the Grail test. I've taken the test that, I want to hear about that. I took the test, which is supposed to test you for any gene sequence that is associated with cancers, whatever that's called. I don't know if I'm describing it correctly.

So how do you want to start this? What does the latest technology tell us about what we can do or how we can do or how we want to modify our behavior based on our genetics to avoid getting cancer. How's that? Well, it's not a foregone conclusion that you have cancer genetics. Could just be the smoking? Yeah, so, I mean, but Dan, you're exactly right. So, you know, when we think about cancer risk, when we think about any complex trait, right, which is, you know, all diseases, right, you know, just behaviors, right? They live at the interface of genes and environment. and they result from the actions and interactions of genetic factors and non-genetic factors.

Cancer is one of them, right? One of these complex traits. So for most of us, the real drivers are non-genetic factors, predominantly exposures and, you know, environmental influences, and a healthy dose of chance, right? For some people, though, the sort of rheostat is shifted away from environment and towards genetics. And these are people who are predisposed to cancer. When we think about cancer predispositions, we think about, for example, Angelina Jolie, right? Who wrote an article in an op-ed piece in the New York Times in 2013. That was really the first time for most people when they sort of heard about or understood the concept of increased risk, genetic risk for cancer. What she wrote about was her mom who had a diagnosis of breast cancer and died before she was able to hug Angelina's children.

And Angelina knew that her mom had breast cancer and that many other women in her mom's bloodline had also had breast cancer and other related cancers like ovarian cancer. And so because she was herself determined to avoid her mother's fate and be sure to hug her grandchildren, she took a genetic test, and she found that she had an inherited predisposition to cancer what we would call a pathogenic variant in a gene called BRCA-1. And so what she was able to do in that case was take action. use that knowledge to mitigate her risk. And so she chose to have a bilateral prophylactic mastectomy, and she also had her ovaries and tubes removed to minimize the likelihood that she might develop at some point in the future of herring cancer. Now, we're going to spend, I hope, a lot of time

talking about genetic risk and highly predisposed families. But when we think about what you've just describes me, meaning your father and your grandfather, both of whom had a history of smoking. And of course, your father spent his life indoors in a smoky cafe, right? Right, right. So exposures were clearly important, right, in increasing their risk of having lung cancer, which is actually a largely exposure-driven cancer, right? So we don't know of really any important genetic predispositions that are associated with an increased risk for lung cancer. So, you know, if you were to say to me, just these two individuals in your family were diagnosed with cancer, you know, in the same bloodline, were diagnosed with cancer.

I would say, you know, especially given what we've just discussed, that, you know, you are what we would call an average risk individual, meaning that you are probably not at increased risk for lung cancer and you don't have to do anything beyond what the normal suggestions are in terms of screening for cancer, right? But I do think that what you were just asking of that is super important because when we think about the guidelines for cancer screening, they're really focused upon what are called average risk individuals, right? People who don't have any red flags for cancer, for cancer running in the family, right? You know, and the reason that that's important is because let's just take the example of breast cancer, risk in women, right? What we know is that an average risk woman should have

a mammary once a year starting at age 40, right? Everybody knows that, right? So, What if you're a high-risk woman, right? So in that case, you get standard of care covered by insurance, genetic testing, and starting at age 40, or perhaps earlier, depending upon the results of the genetic testing. You know, even if you test negative, you would get an annual breast MRI once a year, alternating one or the other every six months with your mammogram, right? And that's for high risk women. So the two important questions are, one, what defines a high risk woman?

And two, how prevalent are high risk women, right? So the answer to the second question is astonishing. It turns out that 20% of all women on planet Earth are high risk for breast cancer. But they don't know it, right? Because their doctors don't ask. So to get to the first part of the question, what defines high risk. It's a combination of personal factors and family factors. So the personal factors are your age, your age at your first period, your age at your first live birth, right, your height,

your weight, then the density of your breasts, then there are family factors. You know, did your, did people in your, in the different bloodlines, your maternal or paternal bloodline, have certain types of cancers, breast cancer, ovarian cancer, prostate cancer, pancreatic cancer. You know, these are just the care, and is the R.U. of Ashkenazi ancestry, which also increases. High risk, yes. Yeah. So, you know, you can basically answer these questions.

It's very simple. online form actually that people can just do themselves and they can determine their individual risk for breast cancer. And the deal is that if they're high risk, meaning have a personal lifetime risk of breast cancer of above 20% as compared to 12.5% in the general population, then you're high risk. And you get all these things, again, covered by insurance, standard of care, but nobody knows about it, right? So the fundamental dichotomy that we have to think about really is high risk versus average risk, because the rules are different.

Right. You say the average risk is 12%? 20%. So average is 12.5%. So that's one in eight women. Well, that's a lot. So what is the average risk of dying of breast cancer? 12.5 to get breast cancer.

Right. Right. So breast cancer is unfortunately still one of the most fatal cancers for women. Now, lung cancer is surpassing it in women, but a lot of women still die of breast cancer. Now, the good news is that we've gotten very good at treating breast cancer. So the vast majority of women who are diagnosed with it are diagnosed with it at an early stage when it is highly treatable. But because it's so common, there's still lots of deaths there to that. So let me just because I think I understood a bit. So 12.5% is the average risk and 20% of women are high risk. Is that right? Correct. Okay.

So, okay. So let me just ask a question about the lung cancer again, because before it leaves my mind. We, all of us, are of the generation who, when we were younger, we were constantly around cigarette smoke. I was around it more because I was a musician during the time we spoke. He was still allowed in clubs. But all of us, we were in cars. I mean, smoking was everywhere.

Our parents smoked, right? Our parents smoked. My mother smoked, but she smoked Carlton's, which, as you know, Carlton is lowest. I don't remember that that was their slogan. So my question is, does that have a lifetime impact on our cancer risk, or does it time out? Yeah, so most likely it times out. If you think about lung cancer screening recommendations, right? The idea is that if you have a personal history of smoking that surpasses a certain number of pack years over the course of your lifetime, then you qualify for annual CT screenings. But if it turns out that you haven't smoked for either 10 or 20 years, then it times out, and you don't need to have this sort of high-risk screening.

Now, that's a relief. Now, getting back to what you said about women, since people are smoking much less than they used to and there's no more, as much less secondhand smoke, why are more and more women getting breast cancer, I mean lung cancer? nobody well so it's not clear that's sort of the simple answer but if you look at demographics what you'll see is that younger people younger women are are smoking at higher rates than they used to probably that has something to do with the risk of lung cancer you know but a lot of what matters is still completely unknown, right? That's the whole field of epidemiology,

which tries to understand the role of these environmental risk factors on risk for diseases or contribution to different outcomes to different diseases. But we don't know. And, you know, we don't know what is exposure-related, what is chance. We don't know if there are windows of susceptibility. So, you know, you talked about us being around smoking as kids, right? Are there developmentally determined windows of susceptibility, right? It's worse to be exposed to smoke in utero, right? Or when we're growing, right, developing, right? Then it is when we're now, you know, well, I'm 21, so I'm fully cooked, right?

You know, but is it worse to be exposed in utero than it is when you're fully cooked, probably? but we don't know the answer and we don't know if it is, in fact, worse, how much worse it is, right? So there are all of these completely unknown, and then there's interactive effects. What about smoking while drinking, right? Or smoking while drinking while standing outside, you know, tanning ourselves, right? You know, we just don't have any clue about any of these factors and how to quantify that in a way that's meaningful. Is there any research on tetraethyl lead used in gasoline when all of us were kids is no longer used? Leaded gas emissions?

Right. So the answer is yes, but I can't really speak to it. It's not my area. Now, we should be on the verge of some like quantum leaps. I mean, AI has the ability to do, it's kind of like group force. you know, just an amazing number of computations so quickly to find correlations. And now more and more people have their genomes, a public record. And I feel like we should be getting some real breakthroughs in terms of finding

correlations between genes and all sorts of things. And we are. So what are getting? So we're getting tons of things. You know, and you can actually think of it as multiple levels. right? So we're getting incredible insights onto the, so let's just step back for a second and talk about the genome, right? Let's talk about genes, DNA, and just how things are organized, right? So our bodies are, of course, made up of cells. So the instructions for our cells are

our genes. There's a total of 22,000 genes. They're exactly the same in every cell of our body and they're unchanging from the moment that we're conceived until we pass away. So our genes are our genes. She themselves are made up of DNA, A, C, T, G. And it stands to reason that if our genes are the same in every cell of our body, so is our DNA sequence. Guess what? It's true.

But if we compare the DNA sequence of any two people, right? You know, Noam, you and me, or Dan, you and no. what you'll find is that have their differences. If at a specific site in my DNA, I'm an A. If we look at that same site in your DNA gnome, you might be a T, right? Those differences are called variants, and each of us has about 10 million of them, strewns or DNA sequence. So 22,000 genes, 10 million variants.

So it's complicated, right? Now, when we think about inherited risk for cancer, it turns out that of the 22,000 genes only a small subset of them, somewhere between roughly 40 and 100 function to defend against cancer. So when we perform a genetic test looking for an inherited predisposition to cancer, we only look at some subset of those 4200 genes. And what we do is we sequence, you know, we take a sample of blood, you know, or spit or a cheek swap, which is just a source of DNA. And remember, it's the same in every cell of a person's body. So looking at your cheek swab DNA looks at your DNA unless you just ate a hot dog, in which case it tells us that you're, right?

And, you know, we sequence those genes. And we run the sequence of those 40 to 100 genes through a con. computer, and what the computer is asked to do is not so much identify variants because there are 10 million of them. We're going to find them. But rather, what it's asked to do is identify a specific type of variant, one that might act as an off switch for one of those genes. And so the idea behind these tests is that if you have a variant that acts as an off switch for a gene that functions to defend against cancer, that will be associated with an increased risk for cancer. right? So that's the test probably known that you were describing that you had before that was clean.

You had some sort of test that looked at a panel of genes that, you know, that was associated, that were associated with an increased risk for cancer. And what you learned is that after the computer inspected each of those genes, none of them had an off switch. Okay. And so what that means is that all the genes were functioning the way that they're supposed to. Okay. So that's genetic testing for cancer, and that's the sort of core technology that we use, sequencing technology. Now, our capacity to sequence, let's a sequence both normal cells and tumor cells, right? And by sequencing a person's normal cells and sequencing that person's tumor cells, what we can do is compare the sequence between the two, right? So what is a cancer cell? A cancer cell is just a normal cell that's

acquired changes that allow it to escape from normal regulatory control and divide unchecked. It's very unromantic, but that's all a cancer cell is, right? And so by comparing a person's normal DNA to that person's tumor DNA, we can identify changes that are found in the tumor. And then the idea is that some subset of those changes are responsible either for initiating the cancer or allowing it to progress, right? Now, Dan, to what you were talking about earlier, cancers and just cells, right, don't lose the capacity. to acquire changes just because they've become cancer cells. And so what that means is that when you have that first cancer cell that divides and grows into a tumor,

actually many of those tumor cells are closely related, but not identical to each other, right? Because they're continuing to acquire these changes, right? And so most of the time, those changes are completely inconsequential. But sometimes they confer properties on those, you know, they result in activation or inactivation of pathways that somehow ultimately confer an advantage on the cell that has that specific genetic change. And if you think about chemotherapy, right, if you, you blast a person with chemotherapy, it's going to kill off the vast majority of cells. But if,

just by chance, there's some cell that remains that has acquired a mutation, right? Some function that allows it to be resistant to chemotherapy, then it's going to survive, right? And that's going to result in a relapse, right? And so what happens with the point, point is that tumors are not static entities. They evolve and they react to selective pressures, right, like chemotherapy. And those selective pressures select for these resistant cells. And, you know, and if you think about a tumor, right, for a tumor to be visible, it really has to be larger than a centimeter. Okay. And if you think about the number of cells that comprise, that comprise a one centimeter size tumor, it's tens of millions.

Wow. And if you think of just evolution, if you think of the Galapagos, right? If you think about just speciation, right? What that means is that even a very small tumor has probably lots and lots of different subclones, right? very closely related, but individually and unique clones that comprise it. And, you know, when you think of it as a problem in evolution, right, with lots of different individuals, it's no surprise that cancers, you know, can survive the therapy that we give them, right?

Because they are not identical, right? the cells are not identical. And sometimes there's an advantage to some of these other ones. I want to ask you. Go ahead, Dan. How does cancer kill you exactly? Yeah, so that is a great question. And cancer kills you by causing something to happen.

And I realized. I told you. Right. I know that's exactly specific, right? I'm sure that gives you the answer you were looking for. But there are different ways that cancers can kill you. So if we think about leukemia, which is a blood cancer, right, your blood is comprised of three different types of cells. It's got red cells that carry oxygen, carry energy to all parts of your body.

It's got white cells which fight infection, right, and allow us to survive, and they also mitigate healing, right? And then we have platelets, which are the cell fragments, actually, that allow us to climb, right? So if you think of a leukemia, which is a white cell that actually doesn't function normally, or is a very early progenitor cell, right, that just explodes and takes over your blood. What kills people with leukemia is generally some sort of overwhelming infection that they can't fight, right? Or this terrible pre-discipline, they bleed, right? Because they don't have these platelets that allow them to clot, right? Generally, it's an infection that kills people with leukemia. If you think about lung cancer, what kills people with lung cancer

is you have this mass in your lung, right, that's growing, and ultimately it's going to grow into a blood vessel, for example, right? And that's going to cause massive bleeding. And that's what's going to kill you the person, right? If you think of a brain tumor, you know, it's going to grow, and it's ultimate, going to compress on the part of your brain that controls your autonomic nervous system, which are things like breathing, heart rate, blood pressure, right? So cancer kills, not because the cancer kills, but it's because it intercepts and deranges something. This is how my father died of brain cancer. I have one more dreary question. Then I have a somewhat more lighthearted question, just on the subject of this. What are, because my father before he died, he had brain

cancer, he had seizures. And I saw one of them was one of the most upsetting things. It was terrifying. Yeah. And he was having them for a while and kept them to himself. But anyway, what is a seizure? What instigates it and what makes it stop? So that's, again, a great question. So You can think of your brain as an electrical station, right? You know, your brain has neurons that sends along those neurons, essentially electrical signals, right? And they become compiled and organized in different regions of your brain, right? So there are different parts of your brain that have different functions, right? That compile and organize these signals in different ways, into thoughts or into thoughts or

into memories or into, you know, again, regulating blood pressure, right? And so a seizure is a disorganized wave of electricity, right? And so what can instigate it is a tumor can instigate it by essentially disrupting those normal pathways, right? It's basically like if you have wires, right, and you strip off the, you know, the, the, the, the, insulation. Insulation, thank you. You know, you just basically freak out that part of brain, and that's a seizure, right?

What stops it, you know, often it's just time, right? Time, just the things, you know, just can't propagate forever, right? But the danger is that, you know, first of all, people, if they're having sort of these large tonic chronic seizures can really hurt themselves, right? If they're driving and they have a seizure, you know, that's obviously a nightmare. But, you know, often when people are seizing, they can't breathe well. And so the brain has periods of low oxygen. And if you think about people who have seizures over and over, those what are called hypoxic episodes just have a cumulative effect on their brains that obviously isn't good.

Dostoevsky had seizures. He writes about it. I don't know if that means he had epilepsy if it's the same thing or not. But he had it and a lot of his characters in his book have seizures. Anyway, this is my question. I'm fascinated with. How do I put it? Like, you know, somebody smokes, smokes, and then they get lung cancer.

And I say to myself, well, at some point, maybe there was one cigarette. The last cigarette that if they had stopped one cigarette short of that number, maybe they would have never gotten cancer. Or somebody has a cancer and said they didn't catch it in time. Say, okay, well, there's actually a minute. There's a precise minute where if they had caught it. it, then they would have been able to save him, and then it crosses, and it's too late to save him. The tipping point. Yeah, a tipping point. And so I'm always desperately trying to avoid being on the

wrong side of this somewhat, you know, unknowable point in time. And when I had this grail test, which is a test for, you know, a gallery test. Yeah, galleries for any kind of early cancer. I fear my family's walking in the back when it had this grale test for any kind of early cancer and I had, it was all clear. So I asked my doctor, I said, well, okay, this is great. I said, should I come next week for another one? He says, what do you mean?

I said, well, it's just a blood test. Why wouldn't I want it every week? He says, well, it's very expensive. I said, yeah, it's not that expensive compared to, you know, dying. I'll spend the money. And he says, no, you can't have it every week. And he gave me an answer because of false positive.

I felt like, and none of those answers really satisfied me because obviously, isn't it just a coincidence at once a year? Like really, everything breaks down. The optimal time just happens to be once a year or, you know, every, so obviously that it's like saying one, six feet of separation during COVID. They don't really know how many feet is perfect, but it's, you know, it's something like that, right? So I guess what I'm asking is, um, these tests, these tests, yeah, why? Why? Don't I get it once a month? Once a month. I know that, you know, go ahead. Why not? Yeah, so the short answer is because they're not ready for prime time. They don't work. You know, that's really the answer.

I don't need it at all. So, you know, these are what are called multi-cancer early detection tests or medicines, M-C-E-D, right? And the idea is exactly what you're saying. You know, we have scans, we have, you know, the prevention things that we were talking about earlier, colonoscopies, mammographies, right? And, you know, they all are effort. They all take time. They're all expensive. They all require us to do things. And, you know, the idea is, wouldn't it be much better if there was a simple blood test that looked for evidence of, you know, dozens of. different cancers that we could just say hello to everybody for me, by the way. You know, you're muted the audio, but they're having a party over there.

They're going to go ahead. You know, that could just look for evidence of lots and lots of different cancers at once and just give us the answer and let us move on with our lives. So the idea is that whenever a cell dies, a normal cell or a cancer cell dies, it sheds DNA. And that DNA, you know, gets cleared in our blood. And so when you take, when you have one of these multi-cancer early detection tests perform, what they're doing is taking a sample of your blood and looking specifically for pieces of shed tumor DNA.

Right. Now, the hope is that if it's there, it'll be detected. and if it's detected, it'll be detected at a time that is earlier, right, then would be detectable by other, you know, commonly's prevention, you know. Before you have obvious symptoms. Before you have obvious symptoms. Or perhaps even before you have evidence on scans, right? Because they're looking in your blood, right, for these tumor DNA fragments.

So that's the idea, early detection, right? So there was a study that was just completed in the UK, just not that long ago, just a few months ago, of the gallery test, the Grail gallery test that asked not, does it work at detecting cancer early, but does it work at detecting cancer at an earlier stage, then could be detected using. regular already existing screening strategies. And the answer was no. It didn't succeed even in detecting cancer at an earlier stage. And so... Maybe that's because they're not giving it often enough. Well, I mean, yeah. I mean, you know, the point with what, you know, there are certainly limitations to the study. It was, you know, it was done in over 150,000 people. It was done you know, once a year and, you know, and they were followed for several years. But so, you know, perhaps if it's done, you know, every year for 50 years, you know, you might see something. But

the point is that it didn't detect, it wasn't able to detect cancer early and it wasn't even to detect cancer at an earlier stage. So the take-on message for me is that it's not ready for prime time, right? You know, in people like you who, I think, are average risk, right? Now, you'll finish your point if you want. I was just going to say, I do think, though, that there may be a role for these early detection tests today in high-risk individuals, right? You know, but that's an open question. The other thing that's important to know is that not every cancer sheds, right? So different cancers break down at different rates. And, you know, some cancers like pancreatic cancer or breast cancer just are very, you know, you don't detect that well

with these early detection tests, right? Well, okay. So your answer is that it doesn't work, which is not quite the answer to, you know, why they wouldn't give it more often. But Let me ask you a question that's related to it. I think it's the more important answer, right? I mean, why would you do something that doesn't actually give you the answer that you're looking for more frequently or less frequently, right? But the question can apply to other tests and things in general. So as- Why not a colonoscopy more frequently, I could ask.

Yeah, let me-that's-so as, and I'm going to bring in something else because I'm always- Well, remember, a colonoscopy works, right? There is evidence that if you identify polyps and you, you know, clip them out, you do prevent colon cancer, right? So what I worry about or I wonder about is that as these technologies become more and more accurate and the false positives become fewer and fewer, that it will make sense to do them every day or something. and it costs a lot of money and this becomes a political issue whereas it's very unbecoming to have the wealthy people you costs it 100% right and so and also insurance you know so this is all something which i think is bubbling up slowly made this grail test turn out not to work but it could have worked right and um i know this is you know this is yeah what's your what's your

thoughts about all that. Right. I mean, I just want to be very clear. The Grail test, gallery test is a very important pioneer in this. Right. You know, there are lots of different companies that are developing lots of different tests and we will solve the problem, you know. I'm not worried about that. And I actually would say that it's likely that we will solve the problem at a point whereby we, right, even ancient folks like us, will be able to benefit from these tests, right? So, you know, not ready for prime time today isn't the same thing as not ready for prime time in five years or something like that, right? And that's super important, right? I'm very confident that we're going to get there. You know, in terms of thinking about how frequently

to take it, to have the test performed, you know, you have to think about how quickly tumors grow. You know, yes, I understand your point about, you know, the last cigarette. This is now and then, right? But the fact of the matter is that that's just not the way that our bodies work, right? To do a test like that more frequently for most solid tumors, to do something like that. more frequently than I'm totally making this up so don't take this as based on any knowledge more frequently than maybe every six months probably doesn't make sense right you know a year is as you were saying earlier is just a reasonable

starting point we don't know what the right cadences is it once a year is it every five years right you know is it going to turn out to be a every six months when these things actually work. We have no idea. We have to get to the point that they work before we can ask about how we can use. When my doctor said to me about, well, you know, the more you take it, the more likely are to have a false positive. I think my answer to him was, yeah, but every day I walk around that it might have been detected

is a false negative. You know, it's like. You're right. I mean, the thing is, right, you know, if you look at these tests, right, And you look at, you know, how often a cancer is diagnosed, even at very large populations, right? You know, tens of thousands of people, you know, you're still only going to see over the course of three years, let's say, a very small number of cancers, right? in a group of individuals, right? And so, you know, let's say there are 15 true cancers, right,

in 20,000 people. I'm making this up, obviously, right? You know, but if your test says that there are 25 positive results, you know, that actually statistically is fantastic, but what it means is that, you know, a positive result is essentially a coin flip, right? There are 15 positives and 10 false positives, right? Even though the absolute number of false positives is not high, it's still huge, right? Yeah.

You know, and that's a problem. By the way, the colonoscopy is on a 10-year time schedule. If I'm completely free of polyps and such today, does that mean that 10 years? time, there's no chance of some, I could be stage four by then? Yeah, I mean, you know, remember there's a huge difference between individuals and populations, right? The point of guidelines are to make population level recommendations, right? And so it's taking into account actuarial tables, risks, benefits, you know, blah, blah, blah,

over the average person, right? Over, you know, the average person amortized over millions of individual data points, right? So the 10 years comes from the fact that if you look at the, you know, occurrence of colon cancer over the entire population, and you ask, what is that if we do colonoscopies every five years versus every 10 years, there really isn't a difference, right? And so because you don't get something for nothing, right? Colonoscopies involve anesthesia. They involve the possibilities of perforations, right?

There are negative things that can happen from even what we think of as relatively benign procedures. Over the population, right? The optimal time is every 10 years. But that has nothing to do with a single individual. where everything is either 100% or 0%. You either have cancer, you don't, right? That's you as an individual, but that's not the purpose of guidelines,

which are really meant to, you know, tell you what to do for the population. And I think that's also a really important distinction, right? Any one person can be the exception to the rule, right? But guidelines are, probabilities, right? You know, and probabilities are for individuals very unsatisfying, but also very hard to understand. You know, and frankly, they don't apply to individuals. We're all dichotomous in terms of our outcomes. Yes, no, dead alive, cancer-free with cancer.

So, and then we're almost done. You know, I, the American medical system is much maligned. I have mixed feelings and mixed experiences with it. So the bad part is, and I'm surprised to be saying this, but it's absolutely true, I've been involved in and witness to a high number of misdiagnoses and mistakes by doctors. There's just no getting around it. And when we were kids, we didn't think of doctors as ordinary humans, but they are

and they made they used to go in the back they had these books that no one else had and they would tell you something and you assume they knew they were talking about and it was even hard

to even pin a mistake on them but now with AI and not just AI but before that just with the ability to like I had a doctor one time tell me don't give your son Pellegrino

because it's bad for his bones you know sparkling water and I'm like watch and I looked it up and there you go and I looked it up And that's a bunch of, it's a bunch of bunk. And I'm like, this is a real doctor told me, you know. But now if I had been, it's been 1979, I would have said, don't drink Pellegrino.

Like how, I would have zero way. You have to go to special medical bookstore even to get those books. So, so, and now with AI, you know, you feed your, your lab results in or whatever. And, and if there's a difference now between doctors and computer, there won't be for long. So, I mean, so that's part of it. But I will say this. I had a cough, a little cough, and I would wake up at night. And for a couple of weeks, every third day, I'm waking up a little,

and this lung cancer thing in it, and I was worried about it. And I emailed my doctor at NYU. I have no special connections, nothing. By 4 o'clock the next afternoon, I had had a scan and a clean, Bill of Health. By 4 o'clock the next afternoon with no special poll or anything like that as an American citizen. And I know, and I hear stories, that people in these other countries that we're told we should be jealous of, they can wait weeks or months for these same tests. Right. So this is all by way of something just like, you know, a stream of consciousness,

but it must formulate thoughts in your mind that you'd like to share with us. So go ahead. Well, you know, I mean, you're, it's, there's so much to unpack in what you just said, right? Yeah. You know, yes, it's true. American medicine is unbeatable, right, in many different areas. American research, our capacity to ask questions and get answers that are clinically meaningful or that drive research. You know, we were talking about sequencing earlier and we didn't even talk about. the fact that, you know, when we have a cancer that's comprised of all of these different subclones,

part of the research that we're doing in my lab right now is actually individually sequencing these clones, right? And it's trying to understand the heterogeneity of tumors, right? So the stuff that we can do is just unparalleled, right? But the problem, the shame, right, of American medicine is what you were alluding to earlier, that it's not available to everyone, right? You know, you say you have no special pull, but in fact, you do, right? You have a doctor.

Your doctor's at NYU, right? You have good insurance, right? These are your special pulls, right? Yeah, no special pull within my cohort, but my cohort is privileged, yes. Right, right. But that's important to keep in mind, because we think about, you know, all of the people who we're fine with not having. health insurance, right? We're, you know, or who, you know, through the exchange, you know,

gamble with their health, right? They take on these policies because they're all that they can afford, but that have deductibles that bankrupt families, you know, you know, that's, that to me is, is the shame of American medicine, right? That we have these things that are, that are, you know, are not equitably available, right? You live in New York City, just by virtue of living in New York City, you have things that are available to you that just don't exist in large parts of the country, right? I mean, many people throughout the country

have to drive hours just to get to an MRI machine, right? In the country, there are less than 100 NCI designated comprehensive cancer centers. The goal of the comprehensive cancer center program, started by Nixon in 1973, was to make available throughout the country, top flight cancer care and cancer research to the country. Everyone should be within two hours of an NCI designated cancer center. Well, you know, you look at the Upper East side and we've got NYU. you, then you, you know, jog up a few blocks and we've got Sloan Kettering.

Then you jog up a few blocks more, and we've got Mount Sinai. And then you jog up a few blocks more, and we've got Columbia. And that's just the east side, right? Right. You know, there's Einstein, right? And so if you think of the fact that they're less than 100 in the country, and, you know, without breaking a sweat, we just named five in Manhattan alone. That's a problem, right?

You know, so there are any ideas to fix it? You know, I mean, you were first in our class. You must know the answer. I can write a five-page essay on it, right? Is the answer money? I mean, well, the answer is money. The answer is redistribution of money from, you know, some priorities to other priorities to me. So, you know, I trained as a pediatrician, right?

And to me, you know, the thing that that matters the most are vaccines and education, right? That's that's foundational, right? So to me, a redistribution of dollars to vaccines and education and, you know, a truly protective national insurance, health insurance, system, you know, are, to me, the priorities, right? Now, you know, we can argue about other priorities, and to be sure, there are lots of ways to spend money, right? I'm sorry, no, you were going to say something. You know, you don't have to worry about me. I'm still the sensible young boy, you remember. I'm not, I'm not anti-vax. As a matter of fact, I'm quite pro-vax, and I'm I think the whole dumping on the American response to COVID is quite overblown.

But my, because that's obviously in the context to all these conversations. But it must, as a doctor, and then seeing like RFK pointed to a position and seeing the nationwide rejection of vaccines, you must, I mean, how do you even process that? think the country's gone crazy. There is a real cognitive dissonance, you know. I mean, I'm sure that both of you are the same way, but I remember standing on lied to get my first COVID shot. It was December of 20.

I was at Mount Sinai at the time. And, you know, I just remember crying, right? And, and, you know, you think about Operation Warp Speed. You think about how we went from absolutely nothing to robust prevention, right, in no time, right? The time, the times is predicting 10 years or something. It's a miracle, right? It's a miracle, right? And the fact that we went from that miracle, right, to the sort of question, right?

And, you know, it's just, it's crazy. I just can't understand it, right? I mean, you know, what more proof do we need than the fact that we're actually sitting, having conversations and not dead, right? I mean, you think about the black death, right, wiping out two-thirds of the world, right, in the 1300s and then the 1600s, right? That didn't happen, right? And that's because of science and medicine and public health and public service, right?

I mean, you know, and to then have where we are now, right, you know, debunked science driving the entire conversation is it's crazy. You know, and I really can't understand it. It's very dangerous, right? Because COVID was kind of a borderline disease and like just by habit sense. first of all, it didn't kill children. You know, that was unusual, as to my understanding of most illnesses. And then, you know, healthy people didn't die so much. But it left us with this reflex now, you know, 40% of the country that the next time,

God forbid, we need the country to embrace something and it might be much quite more serious. We worry about them rejecting it. And, you know, when they reject it, it doesn't just put themselves at risk. I know you know this. It puts us at risk, right? It puts everybody at risk. Yeah. No, I mean, and, you know, that's the hurt effect, right?

You know, you need a minimum proportion of a population to be protected in order to damp down the likelihood that an infection will spread and thereby protect all of us. You know, and you see the consequence of, you know, measles, right? Yeah. You know, it's, it's just weird. You know, the government, you know, I've always been a believer in big government, right? The government, in my opinion, has always existed to protect us from our worst selves, right? I believe in the government. You know, that whole construct is, you know, in my opinion, being subverted, right?

and um i mean i i know i own a small business so the government to me is the enemy but um but you know what i'm neat right of course of course it you can i call you dr ken you know that's like a tv doctor name but right you we're talking about it up dan so go ahead i'll give you the government health the universal health care system like in canada um this is obviously well it's not such an easy sell to to to working class people but it should be but is there any way to sell it to a guy like Noam? Noam can afford great insurance. Universal health coverage will mean more taxes for him

and maybe a somewhat degraded quality of care. Right. I mean, this is the tension, right? How do you learn the lessons from Canada, from the UK, right? And conceive a better model, right? You know, what is there a hybrid that? might work, a way of, you know, ensuring safety care for everyone, a bare minimum, you know, standard of care for everyone, right, while allowing individuals to also have private insurance,

right, that, you know, has X, Y, or Z that's attached to it, right? You know, go ahead, finish it, because I have another comment upon that. Go ahead. Go ahead. No, I don't really have more to say. So I want to add to that because I find this fascinating. So as an analogy, we all know the tremendous potential of like compound interest. And it always boggles the mind that, you know, if you have money or something, a growth of 3% as opposed to 4% over a relatively short time, the difference is tremendous. Yeah.

Yeah. So like in programs that slow economic growth, so let's say, well, we can do this, but it'll slow economic growth from 3% to 2.5%. We say, that's not much, but actually 20 years from now, that has a tremendous effect and a tremendous impact on the people who live 20 years now. All of my wish is to say that any of these programs that we think are good for health care, more equitable, to the extent that they slowed down the research and develop, in any way by half a percentage point, 10, 20 years from now, you're having a drastic effect on the health outcomes of people who are not yet sick and people are not yet born. So it's a very weighty matter, you know,

and it's very tough to unwinding. Those people don't even live yet. I can't worry about them, but you know, all of a sudden, you have kids and they're saying, and they're saying, say, boy, if we had done that back then, Because technology, I guess, was the subject, what I'm saying, technology grows, in my opinion, kind of like compound interest.

It builds on itself. And it, yeah, so, yeah, I mean, if somebody could have figured this out, some country would have figured it out. As you said, it's just a tension. The tension will always be there, and we'll swing back and forth a little bit. But, I mean, America is the driver of medical technology

on planet Earth, right? And so in some way we wouldn't be if we had a different system. That's right. You know, and you think about the knowledge that has come from our system, and you think about, we were talking about the gallery trial from the UK, right? There's different types of studies that they can do that we can't do. They can do the population-based studies because the national health system gives them also a national health record so they can track people in a way that we can't track.

You know, so in terms of pushing forth knowledge, the two are synergistic. I am quite interested in this topic. I'm almost obsessed with it. It was a wonderful excuse to reconnect with you. And I couldn't be more pleased to see what a pleasant vibe you have and how open and friendly you are, like I remember you, but you know. And you're not in New York anymore, right? I am, actually. I'm kind of, right? So I work now at the Roswell Park Comprehensive Cancer Center, which is based in Buffalo. You know, we were talking about the five cancer centers in New York City. We're the only cancer center in all of Western New York. Wow. Yeah. And so it's a big area. And so I'm the head of genetics and genomics here.

And I have a center, the Center for Precision Oncology and Cancer Prevention. And I'm here in Buffalo Sunday through Friday, basically, or Sunday night through Friday night. I live on the Opry side. Oh. Have you been to Ella's Cafe on Second Avenue? Ella's Cafe? I recommend it on Second Avenue and 74th Street.

I don't know if you're in that area. Very close, actually. But, you know, I did have a, I know I must have to wrap it up, but I had a question. Go ahead, Dan, go ahead. Well, here's something that fascinates me. It's not to do with medicine. It's more to do with psychology. How do you tell somebody that it's over, you know, that they got three months, four months,

or do you not do that? You send somebody else in there? Yeah, well, I think so right now, you know, clinically, What I do is cancer risk. So, you know, we're talking about BRCA, Angelina Jolie. That's what I do right now. But I'm trained as a pediatric oncologist.

So I've spent my whole, you know, previous career, taking care of kids and families with cancer. And so there definitely comes a point where, you know, you have to say that, you know, unfortunately, we don't have anything left to offer, and so we need to think about things a little bit differently. And, you know, to your point about sending someone else in there, never, you know. If you are the doctor, if you're the doctor that has been taken care of that child or that family, it's your responsibility, morally, ethically, everything, to be the one who has that conversation.

And you have to do it in a way, you have to do it. There's no way to do it. But I think that, you know, in sitting down, open-ended, time unlimited, you know, you just sort of lay it out there. and, you know, it's important to give whoever you're talking to the opportunity to digest and to react and to ask their questions. And, you know, it's our job to be there, right? And you say you have a golf game at noon and you're dropping the news at 1130. Oh, come on, yeah, come on, come on. He can't answer that.

We're comedy club, but he has. you know, he has to maintain a thing. I can't even imagine how you deal with things that weighty. I suppose maybe you get used to it. This is one of the best and worst things about human beings that they get used to things, even terrible things. But I think that I think you ever get used to these things, right? I mean, you know, one of the things that when I was doing pediatric oncology, one of the things that I loved was that, you know, I had, my clinic was one day a week and it was cancer risk. And I was the attending, so the chief doctor for the kids in the hospital four weeks a year. And, you know, I loved the fact that I could be all in.

and then, you know, then I would sort of go back to my regular job, which was mostly research, right? You know, but I think that for me, that emotional availability that having, that only having four weeks a year, you know, permitted me was incredibly important because it really did let me be present completely. I don't know. I think it's, I think it must be very difficult for people who are primarily clinicians in oncology, you know, to, to go on. Not take it home with them and be able to live their life. Right, right. I mean, but to me, one of the really important parts of one of important things was being

able to let it all in, right, and to really be a person for my families, right? I love doing that. One of the things I love about cancer risk is the same thing. You know, that the relationship that you get to build with your families, you know, the stakes are incredibly high for them. And I get to be part of the family. And I get to be part of what helps them go through the entire arc of whatever, right? and just that is just such a privilege.

You were obviously born to be a doctor, and what you're talking about as I tell my father's death and I dealt with other serious medical, not my own, thank God, but been around it. It's so consequential when you have a doctor who you feel is available, cares, patient, compassionate, you know, and what we used to say, bedside manner. And when you do find one who's stiff and harsh and, you know, and you can just tell, it's just, you say, why did you even

become a doctor? Like, this is the wrong profession. You might be smart. You might have all the intellectual tools, but it's more than that to be a doctor, or at least to be seeing patients, right? And it's, I think, obvious anybody watching this. that you are, you're cut from the right cloth to be a doctor. I can, since you are in New York, let's, let's get, you know, a drink or I don't know, dinner sometime. I would love that. I think that this is phenomenal.

I'm just so excited to have reconnected with you. You sent me an email maybe 10 years ago and I answered, but we never sort of picked up the thread. So this is phenomenal. Well, I wonder why that is, Noam, because you're usually pretty good about keeping old relationships going. What is it about the doctor now that you just sort of put you off all these years? I don't remember. I'll look it up. I'm sure I still have it. It could be possible. I missed the email, which I do with some regularity. But whatever. We're still young. and that would be really nice to get together.

And I will also send you the video of the boyfriend, our class musical. That would be a little scary, but I'm looking forward to it. Oh, no, you're going to get a kick out of it. You're going to get a kick out of it. All right. Dr. Canaan O'nell. We managed to go a whole... Huh?

Well, I said we managed to go an entire podcast without mentioning Israel, which is... Yes, yes. I just mentioned. Honestly high school alumni, an old friend of mine. This has been a wonderful interview. Thank you very much, sir. We'll see each other hopefully soon. I'm looking forward to it.

When are you back from Maine? That's not clear, but for sure, by the end of August, I'll be back in Maine. Well, don't you want to be back, but no, I would imagine you'd want to be back in New York for the opening of the grand opening. I don't think it's opening in the summer like we're supposed to. We're building a new club, and this is where the, you may love your big government, but I don't love it. I'm not getting open. All right. So I'm going to go eat my lobster, though.

And lobster's okay for you, I think. It's not carcinogenic in any level? Lobsters are great. All right. Mostly great because they're delicious. That's true what matters. And of course, I see. this as a Jew who's mother

from Israel. And maybe you want to come on next week and talk about the Palestinian-Israeli conflict. I'm sure that'll be great for your career. We could do that privately. All right. Good night, everybody. Dr. Ken, as Dan has coined it, Dr. Ken, good-night, good-night.

Good night. Thank you very much. This is amazing. I'm going to show Stuart what he called him next week. I can't wait. Say hello for me. I will. I will. Good night, sir. Bye.