Making Sense with Sam Harris - #98 — Into the Dark Land

Episode Date: September 21, 2017

Sam Harris speaks with Siddhartha Mukherjee about his Pulitzer Prize-winning book, The Emperor of All Maladies: A Biography of Cancer.  If the Making Sense podcast logo in your player is BLACK, you can SUBSCRIBE to gain access to all full-length episodes at samharris.org/subscribe.

Thank you. of the Making Sense podcast, you'll need to subscribe at samharris.org. There you'll find our private RSS feed to add to your favorite podcatcher, along with other subscriber-only content. We don't run ads on the podcast, and therefore it's made possible entirely through the support of our subscribers. So if you enjoy what we're doing here, please consider becoming Today's podcast, I think, is a really important conversation. It is a conversation about cancer. And before you decide that you don't feel like listening to a conversation about cancer, please reflect on the fact that you or someone close to you will almost certainly get it. This is just a virtual guarantee. My father died of cancer. I've had friends die of cancer. Someone in my own family has cancer now. This is just all around you, whoever you are. And today's guest is one of

the great authorities on the topic. You've heard him before on the podcast, but today I'll be speaking with Siddhartha Mukherjee about the topic with which he is most closely associated. Siddhartha is a cancer physician and researcher. He is an assistant professor of medicine at Columbia University and a staff cancer physician at Columbia NYU Presbyterian Hospital. He's a former Rhodes Scholar. He graduated from Stanford and Oxford, where he received a PhD studying cancer-causing viruses, and from Harvard Medical School. And his laboratory focuses on discovering new cancer drugs using various biological methods. He's published everywhere you would expect, but he's also a regular writer for The New Yorker. And he has won the Pulitzer

Prize for his book, The Emperor of All Maladies, A Biography of Cancer. And our conversation ranges widely from his experience as an oncologist, asking many questions from both a patient and doctor-centered point of view, how to think about a cancer diagnosis, the biology of cancer, how the mapping of the human genome has changed our understanding of cancer and the possibilities of treatment, how cancer spreads. We talk about whether we're always getting cancer and the possibilities of treatment, how cancer spreads. We talk about whether we're always getting cancer and simply fighting it. We talk about the difference between remission and cure. We talk about how much of cancer is due to environmental causes. There's a lot here, and it was great to steal another hour of Siddhartha's time.

So, without further delay, I bring you Siddhartha Mukherjee. I am here with Siddhartha Mukherjee. Siddhartha, thanks for coming back on the podcast. My pleasure. Thank you. So, the last time around, we spoke about your more recent book, The Gene, which was fascinating and also led us a little further afield than at least you realized we would go. I had just come fresh off my controversial podcast with Charles Murray, and then led us into a discussion about the genetics of intelligence or suspicions of such and exhausted both of our interest if not our patience on that topic. I won't do that again this time

around because we're talking today about your book for which you are certainly best known and for which you won the Pulitzer Prize, The Emperor of All Maladies, a biography of cancer. And you are an oncologist and spend a considerable amount of your time working with patients and also doing research into the biology of cancer. So I'm really looking forward to having this conversation because we only had about 10 minutes last time around to touch on this all tootoo-important topic. First, before we get into the biology of cancer and treatment, what's your story here in terms of how you got into becoming an oncologist? People tend not to think about how the different medical specialties

dictate a very different experience from the side of a doctor. I can imagine that being an ER doc is not at all the same as being a dermatologist. I mean, you don't get calls in the middle of the night when you're a dermatologist. You're not constantly seeing people die. I would imagine you're dealing as much with human vanity as with actual health concerns. First, what is the experience of being an oncologist? Because it seems like it would be emotionally very challenging. And how did you decide to take this on yourself? So I came into cancer medicine a little bit in reverse. In the 90s, I was at Oxford. I was training as an immunologist, my graduate work is in

immunology. I was interested in vaccines, you know, this is a time when the immunology revolution was taking off. And it was researchers, the biology community just figured out some of the most important things about how the immune system works, how it might allow for enable vaccination and so forth. So I went to Oxford and I studied viruses. I was an immunologist and a virologist by training. The one particular virus that I got interested in is actually a major human pathogen called Epstein-Barr virus, EBV. And part of the reason that we still deal with it is that it's one of those strange viruses that lives in the human body,

but doesn't seem to cause overt disease. I'll come back to the word overt in a second. But virtually all of us have Epstein-Barr virus. This is a virus that's evolved with us, with the human species for tens of thousands, hundreds of thousands of years. And maybe 70 to 80% of people are infected in some parts with EBV. And it seems our immune system doesn't seem to reject it. We never clear it during our lifetime. So the question I was interested in is, why is it that we don't clear Epstein-Barr virus?

Whereas if you have influenza, if you have the flu, you get the flu, your body clears the flu, and you don't have flu virus left in your body. What's the difference between these two things? Why is it the flu gets cleared while EBV remains persistent? And I tried to solve it. I partly, you know, I helped partly solve that mystery. But then it became obvious to me, if you read the epidemiology of EBV, it turns out that in fact, this word, it doesn't cause overt disease.

But in fact, there's a long history of it being linked to various cancers, including lymphomas and other cancers. In fact, the links between EBV and cancer are quite deep. And so I became more interested in cancer, began to think more and more about cancer, cancer genetics. Why is it that what genes in EBV allow it to do the things that it does? Why is it able to stay persistent in the human host? And so I became interested in cancer. And as I became more and more interested in cancer, became more and more interested in going to, you know, thinking about cancer medically, and then became an oncologist. So I sort of did my, I came into cancer through the world of science and immunology.

And it's only interesting because immunology, as you might know, has suddenly come alive in the world of cancer again. The question you asked is, you know, what is it like to being, what is it like being an oncologist? Well, it's very unlike the examples you gave. very unlike the examples you gave, very unlike being in the emergency room. Because you need to, things change extremely quickly. The things that I knew were absolute certainties in 10 years ago, five years ago. So I think one of the things about being an oncologist is that you, the amount of information and the rapidity with which it changes is striking. Things that I knew as absolute certainties 10 years ago are up in question now. You know, 10 years ago,

if someone told me that we would be manipulating the human immune system to reject cancers, I would say, ah, chances of that being true are pretty minor. 10 years later, you know, that's the new direction of cancer. So that's one of the surprising things. like a surgeon might, or as often as a surgeon might, but you stay up in the middle of the night because you're finding out new things that wouldn't be the case 10 years ago. Do you work with children as well, or only adults? I do all my work with adults, although, you know, within the world of cancer, leukemia is one area that I particularly am interested in. It's a funny, it's a funny story, Sam. The leukemia for the, for the longest time, blood cancers led the charge

in the science and treatment of cancer. And what we can, we can explore why there's sort of deep reasons why. And then now the world of cancer is moving beyond leukemias and looking for, you know, how to take those lessons and learn them in solid cancers like breast cancer and lung cancer. So I see both. I see all. I see, but mainly I'm still interested in blood cancers. The history here, again, I'm now focusing not so much on the disease, but on the doctor-patient experience. There really was this amazing stigma associated with cancer. I recall a story about my own grandmother, who I never met, who died before I was born, where she had metastatic melanoma and was in the hospital really to die. But I believe it's true

to say that she was never told her prognosis at all. In fact, she was lied to about what it was. I think she was told she had arthritis and would recover. I mean, it's just something so unthinkable at this moment. It used to be, I don't know how widespread this practice was, but I've heard from many other sources that it was routine for doctors to lie to patients about their prospects, especially women patients, and this was sometimes in collaboration with their husbands. And there was one point in your book where you painted a picture, a very flattering picture of one of the people you studied under, I believe it was Thomas Lynch, a lung cancer specialist, and you described him

as a kind of virtuoso of telling people bad news. But there was a kind of, correct me if I'm wrong, but there seemed to be a kind of necessity of shading the truth even there. How do you think about this? What was the practice then and what is the practice now in terms of delivering bad news in a context of real uncertainty? Because it seems to me that oncologists must, in many cases, take refuge in uncertainty. Because even in the most dire circumstances, there are still these stories of the outliers, the less than 5% cases where someone makes a recovery even from some fairly dire stage four diagnosis. It's a complicated issue, as you point out, and it's an important question. And I think the capacity to take refuge in uncertainty is an important philosophical question, actually.

I mean, you know, to what extent are human beings allowed to take refuge under uncertainty? And to what extent does that become a kind of opium? So I think oncologists have very individual styles around this. But the one thing I think you learn in cancer is that hope is negotiable. And that you navigate your way through an individual's journey, your patient's journey through their cancer. I think the most important thing that I try to convey to patients, and I think the field has tried somewhat now, is to convey that uncertainty without sort of washing it up and cleansing it and sterilizing it. And that's a tough question. That's a tough thing to convey because on one hand, there is the hard statistics. But on the other hand, there are the individual truths, whether you lie within the distribution of patients who

are likely to die in five months or whether you will be the one, your patient will happen to be the one who will survive that time. I think that the most honest way of dealing with it is to imagine this as a process. That on day one, when I meet someone, I can give them the bare statistics. And then I try to also describe what the outliers look like. Who is an outlier? Why I think they were outliers.

Is it because of the location of the cancer they had? The genetics of the cancer? The genes that the cancer, the mutations? Is it because they happen to have a particularly successful surgical resection? Is it that they were the best responders to that particular chemotherapy? So I try to describe that. And I tell people, honestly, that I don't know where they will sit, but the curve, the the mean the medians look like this and then in time the next time i meet them i know a little bit more um and so i'll modify uh my understanding if you wanted to have a formal name for it this is bayesian statistics it's a wise

way of thinking about the world when you take your priors and you modify your priors to make conclusions about how these people, how individuals will behave, given the circumstances. I think, and I've written about it, I think Bayes' insight into the world, Thomas Bayes' insight into the world was very profound. And medicine is still trying to deal with it. We're coming to terms with that idea. Again, in terms of your emotional experience as a physician, I remember at one point in the book, I think you were describing what it was like to be a resident at that point. I don't know how it's since changed, but you were talking about a kind of professionalization of your emotional range in the presence of these distraught families or patients for whom you have to deliver very scary news. And you were talking about that as a kind of necessity, but also as perhaps a psychological or ethical error. I mean,

you obviously weren't comfortable with this change that was coming over you, how this was becoming, you had a routine way of distancing yourself from the pain, you know, or just kind of dampening down your empathy so as not to be bowled over every time you had to talk to a very sick patient. How has that evolved for you? And is there an optimal way of being in that role? I don't know if there's an optimal way of being in that role, but I think that the conflict that you're talking about is very important because the professionalization of empathy is a rather dire thing, as you can imagine. It creates all sorts of internal conflicts. I mean, you know, there are now classes which hope to professionalize medical empathy.

There are good things about that. There is a kind of importance to sensitivity training, if you want to call it, you know, it's an Orwellian word, sensitivity training in medicine. But that said, I think there's also a regret that people have that the spontaneity that you had when you were a resident, when I was a resident, when I was an intern, to be able to tell people sort of, you know, honest news about themselves is somehow being filtered. You feel as if there's a filter that's come into your life. I think I personally try to resist the filter. I try to maintain the honesty. I told you my method. the filter. I try to maintain the honesty. I told you my method. My method is to think in,

if you want to call it formally, a kind of Bayesian way about medicine. I think that helps. It allows you to maintain a kind of personal honesty in the face of... So when someone says to me, am I going to die in five months? You don't resort to the kind of, you know, nonsense speak of, you know, of a professionalized empathy training in which you, you know, hold their hand and pretend to be aggrieved. You try to assess yourself, what your own feelings about their impending death is. You try to understand, you try to help. I think it's a real struggle. And I know like many disciplines, the exaggeration can ultimately, the exaggeration of false empathy is detected by patients very quickly, and they shut themselves off. The last thing they want to hear is false empathy.

So I think you're pointing to an important struggle that's very much inside the discipline. And they also probably don't want a physician who bursts into tears and begins sobbing on their shoulder when he delivers the news. So there's not... So you can't be clear-eyed when your own eyes are clouded with tears. So I've written a little bit about this. I wrote an essay for The New Yorker on numbness, which is about this idea and about trying to connect life as a doctor and how it benumbs you. The fastest response to living as a doctor is to shut it down, to become numb to all the enormity of the suffering. And I was, there is something in, one of the connections I sought in that piece was to Chekhov, who was a doctor and a writer, and about his capacity to remain

clear-eyed about the world without shutting off, without becoming numb to it. It's a pretty tough act, but I think we try. Yeah, well, it's just amazing to witness. I also watched the documentary based on your book that Ken Burns produced. And again, given this is so far outside the range of my professional experience, I just was amazed at what oncologists have to go through as their patients go through the scariest moments in their lives. And especially when you're talking to the parents of children who have received a diagnosis of leukemia or some other cancer. It was just so lacerating for me as a viewer. It was very difficult for me to watch until I just kind of surrendered to it. But basically, for me, of course, the point that you're making is incredibly important, which is that you cannot, no one wants a sobbing doctor. And you want someone, you know, there is a fundamental, and I suspect that I will

raise some hackles as I say this. There's a fundamentally, the fundamental relationship between a patient and a doctor, even today, the power lies in one direction. The doctor knows that the patients are there to try to seek help. That is not to say that that's a good thing. It is just to remind ourselves

that there is a, that the, that empathy can be helpful. And of course, there's a prerequisite for medicine, but false empathy and, and trying to, trying to, trying to, trying to emulate the actual experience of the patient as a doctor is going to be necessarily flawed. You, you are not the person with cancer. It is the person sitting in front of you that has the real problem. Actually, there's a good distinction. I don't know if you know the psychologist Paul Bloom at Yale. He's done a lot of work on empathy, and he wrote a very

controversial book entitled Against Empathy, where he differentiated what he calls cognitive empathy, just understanding what another person's experience is, and the more emotional contagion style of empathy, where you just find yourself crying when you see someone is sad. I think in this case, he would say that what we want are physicians who have a lot of cognitive empathy. They know what you are very likely to be going through and they care to alleviate your suffering, but they're not being held hostage by their own emotional reaction to suffering vicariously through you or thinking about, you know, how would I feel if it were my kids I was talking about and all of that. about how would I feel if it were my kids I was talking about and all of that. Absolutely. And it comes down to, again, very, very important basic things.

In the laboratory, when we study cancer genetics or study cancer cell behavior, you're abstracting away so much from the experience of the illness. But it's important to remember the experience of the illness lived through the lives of your patients as well. It's what motivates a laboratory life, at least for me. So I think it's very important. I think in the distinction, I've certainly read this distinction between the cognition of empathy, the cogitation of empathy, and the enactment of it. And I would agree that I think that's an important distinction. And I think it's a struggle. It's not simple. I don't think, you know, I would be lying if I said to you that one doesn't bleed into the other

quite quickly. And this, I think, goes back to the idea across the board that in a behavioral sense, you can teach being a doctor. But of course, that's just merely in a behavioral sense. What does it mean to behave? What words do you say? But patients very quickly pick up the idea that you're saying them without believing them. So believing it, believing inside what it means to have, if you want to call it cognitive empathy, is a psychological realm, which is actually quite deep and understudied. Actually, we don't fully understand it. Is there anything that you know from the side of being an oncologist that you think cancer patients or their family members should know but often don't in terms of the experience of receiving a diagnosis and going through treatment and

talking to their doctors? Is there any question you would ask your doctor or anything you would do differently given how much you know about what it's like to be an oncologist and what the full course of treatment often is? And I mean, just what does your experience give you as a prospective cancer patient that most people don't have? Well, one of the things I'm thinking of an important essay, which I often encourage patients to read by Stephen Gould. Well, the median is not the message in which the backstory is that Stephen J. Gould was diagnosed with a very unusual cancer of abdominal mesothelioma. And if you read the statistics, Gould's prognosis was extremely grim. It was very, very sobering. And the question that Gould asked himself in this essay, and I encourage people to read it,

is if you take the curve of survivorship, so if you just plot as you can plot the number of patients who are alive five months, seven months, 12 months, 20 months after the diagnosis. It'll look like, it might look like a Gaussian curve, but it might look like any kind of curve. The question you want to ask yourself is, where are you located in that curve? Are you on the side of the kind of person who is going to the side of the kind of person who is going to rapidly succumb to this cancer? Are you likely to survive the batterings of surgery, radiation, and chemotherapy? If you do, what are the chances that you will survive this with a meaningful life, et cetera, et cetera? So he tried to place himself. And once he had placed himself in that curve, he was able to make decisions about treatment more accurately.

So if I were to become a patient, and I will, I mean, statistically speaking, you and I will both likely have cancer. You know, one in two men, one in three men, one in three women, pardon me. And again, statistically speaking, there's a good chance that we will die of cancer. So if I were a patient, I would try to ask when I was sort of sitting on the other side, um, of the desk, as it were, I would try to locate myself as Stephen Jay Gold did and say, what's the likelihood that I will be one of the few people who will succeed with some kind of novel therapy versus the chances that I won't. And once I know that I might be able to make decisions thoughtfully, the questions that I like to ask myself is, what are the strong endpoints that I should stop treatment? I'd ask

my doctor that. What are you looking for when you would say to me, you know, I think we're getting to the point of time that we would better consider, seriously consider a hospice, seriously consider the withdrawal. What are those endpoints? And in the opposite sense, what are the things that you're looking for that would tell you,

this is a kind of patient that I would rather treat more aggressively, treat more proactively than with chemotherapy. This is not to say that hospice and palliative care are not proactive treatments. Please don't make that, let's not make that mistake. But this is just to remind us that that's the direction. Those are the kinds of guidance that I'd like to know. I mean, and it could be hard science. It could be genetics.

It could be, you know, the microenvironment. It could be the nature of the tumor. I'm looking for a hitchhiker's guide to Bayesian cancer. Right, right. The fact that so many people are dying of cancer and will continue to die from cancer is, in some perverse way, good news, because it shows that many of the diseases that killed us before we even had a chance to get cancer have been cured or at least beaten back into submission. Let's talk about the disease itself, and I'm sure there'll be other questions that could come up here relevant

to the patient experience, because as you say, virtually everyone will either get cancer or have someone close to them get it. So, the simplest possible question, for which no doubt there is no perfectly simple answer, but what is cancer? Cancer is a family of diseases that shares the common cause of its own. If you'd like to continue listening to this conversation, you'll need to subscribe at SamHarris.org. Once you do, you'll get access to all full-length episodes of the Making Sense podcast, along with other subscriber-only content,

including bonus episodes and AMAs and the conversations I've been having on the Waking Up app. The Making Sense podcast is ad-free and relies entirely on listener support, and you can subscribe now at SamHarris.org. Thank you.