‘A Many-Headed Beast’: Telling The Story Of Cancer

FLORA LICHTMAN: Hey, I’m Flora Lichtman, and you’re listening to Science Friday.

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Today in the podcast, how do you write the story of cancer?

SIDDHARTHA MUKHERJEE: If you want to understand your disease in a metaphorical way, if you want to think of it as an enemy, think of it as an enemy. If that’s harmful to you, if you feel as if that’s going to hurt you, don’t do it. There’s no one way of thinking about cancer.

FLORA LICHTMAN: 20 years ago, a young oncologist, overwhelmed by the intensity of treating cancer patients, started journaling to process his feelings. That cathartic act eventually turned into a Pulitzer Prize-winning book that fundamentally changed the way that millions of people understand cancer, The Emperor of All Maladies.

The book turns 15 this winter, and its author, Siddhartha Mukherjee, is now one of the most celebrated modern science writers. We’re talking with Sid about how our understanding of cancer prevention and treatment has evolved and how his understanding of cancer has changed too. Sid, welcome back to Science Friday.

SIDDHARTHA MUKHERJEE: Thank you for having me.

FLORA LICHTMAN: You study cancer, you treat cancer, you write about cancer. And I want to start with a writerly question. How do you think about cancer narratively? Is it a character to you? Is it a David and Goliath story? And how is that story changed since you wrote the book?

SIDDHARTHA MUKHERJEE: Well, the story’s remained, in some ways, the same. The closest I can describe it, as close as I can describe cancer, is a many-headed hydra. It’s obviously something that’s penetrated our lives in very complex ways.

We say something is a cancer in our social lives. We use it as a metaphor for everything that’s wrong. “Malignant” is a word that we use as a metaphor for everything that cannot be easily destroyed and is destroying us. And so there is no one cancer. So I think about it as a many-headed beast. Some people occasionally say, thinking about cancer metaphorically or even anthropologically is problematic.

FLORA LICHTMAN: Why?

SIDDHARTHA MUKHERJEE: Well, I think they think that it sort of takes a disease and makes it into a metaphor or makes it into something that it is not. And my usual answer, to patients especially, is use what you want to use. If you want to understand your disease in a metaphorical way, if you want to think of it as an enemy, think of it as an enemy.

If you want to think about your journey through cancer as a battle, do so. If that’s harmful to you, if you feel as if that’s going to hurt you, don’t do it. There’s no one way of thinking about cancer, just like there is no one way of thinking about any disease.

FLORA LICHTMAN: Well, that’s– I wanted to ask you about that because we often hear it’s not one disease. And at the same time, there is a center, right? And very recently on the show, we talked about animals that don’t get cancer or don’t appear to get cancer. And it makes you think that, even though it’s not one disease, there must be ways to prevent all cancers.

SIDDHARTHA MUKHERJEE: Well, this is the strange– I wouldn’t say it’s a paradox, but it’s a strange reality, which is that cancer is, as you very well and often has been described as really hundreds of diseases. But there is a commonality between them. And the center of what I’m trying to prevent, treat, or cure is an aberration, a genetic aberration in cells. And it’s important to stress that commonality because it’s these commonalities that are often what we’re trying to target in terms of preventing and treating cancer.

FLORA LICHTMAN: I want to talk about this disturbing trend of young people getting diagnosed with certain cancers, colon cancer, rectal cancer, at higher rates than before. Do we know why?

SIDDHARTHA MUKHERJEE: We don’t know why. And one very important thing that I point out in the book is that, in cancer, especially in cancer diagnosis, it’s very important to distinguish between reality and statistical mirages. So I’m almost certain that the increase in diagnosis of colorectal cancer in young men and women is not a statistical mirage.

But occasionally, you’ll see things like because there’s a new diagnostic test that comes up, all of a sudden, the incidence of a certain cancer goes up. And that’s only because you’ve introduced a new test, and it’s diagnosing people earlier.

So in the case of colorectal cancer in young men and women, I don’t think that it’s a statistical mirage. I think it’s real. We still have to find out whether these cancers– how they behave because not enough time has passed. So we have to find out whether they behave badly in the sense that they invade. Do they cause death, do they cause disability, and so forth?

The question of why is an incredibly important question. One of the things that I point out in the new version of the book is that we’re slowly discovering a whole class of new carcinogens, cancer-causing agents which cause cancer not by causing genetic mutations in cells, but rather by changing the environment, the soil in which the seed of cancer grows. So these are carcinogens that often act through inflammation. And then they enable previously dormant cancer cells to start growing because they create an environment which is a soil which is pro-malignant, a pro-malignant kind of soil.

FLORA LICHTMAN: Give me some examples.

SIDDHARTHA MUKHERJEE: The most recent example, which is really fascinating, is air pollution. So microscopic particles of air pollution, the smallest kind, we now have very strong evidence that shows that these air pollution, which we didn’t fully understand as a carcinogen, causes cancer, most likely by causing inflammation in the lungs. The particles lodge into the lungs and cause a very particular kind of inflammation.

It’s very important to emphasize that it’s not just– we use the word “inflammation.” It’s kind of a–

FLORA LICHTMAN: Yeah, It’s a broad term, yeah.

SIDDHARTHA MUKHERJEE: It’s a broad term. But this is a very particular kind of inflammation. And this is the kind of inflammation that allows cancer cells to grow. Now, I can’t emphasize how important this news is because all of a sudden, instead of looking for things that cause genetic mutations, which are also carcinogens, like X-rays, for instance, or formaldehyde– these are carcinogens. But instead looking for mutation-causing, genetic mutation-causing carcinogens, we can start looking for inflammagens, things that cause inflammation in this particular way, and use a whole new series of tests to find them.

So the field is, I would say, in some ways, aflame again in a way that it has not been for many years. And so this reinvigoration of carcinogenesis, or the understanding of carcinogenesis, is very exciting because as you know, prevention is the most important way that we can deal with cancer.

FLORA LICHTMAN: There was a study just recently tying colorectal cancer to processed foods. Do you think diet has been overlooked as a variable in cancer?

SIDDHARTHA MUKHERJEE: Absolutely. I think diet has been overlooked. In fact, one of the things that I do scientifically in the laboratory is to look at diet both as a potential mechanism for treatment of cancer as well as a potential mechanism for causing cancer. And I think diet has been overlooked partly because dietary surveys are notoriously difficult. And that’s because the essence of what a diet is ultimately, obviously, a series of molecules.

But those molecules come in various different forms. For instance, you can have excess processed fat in your diet because you’re eating, I don’t know, Cheetos. [LAUGHS] Or you can have excess processed fat in your diet because you’re eating some other substance.

So it’s the molecules that are ultimately driving, or potentially driving, the risk of cancer. But a dietary survey doesn’t know how to capture molecules. It can only capture what you’re actually eating. So it’s a notorious problem and, in fact, interestingly, a kind of problem that AI can solve because it can deconvolute the very complicated diets that people eat. And if we could just deconvolute them and understand the risk of cancer, this would be an interesting problem that one could solve.

FLORA LICHTMAN: Hm. Let’s talk briefly about screening. I know that you have a nuanced view of screening. And I think it might surprise people that you’re not always pro-screening.

SIDDHARTHA MUKHERJEE: Absolutely. And I think it’s very important to have a nuanced view of screening. So we hope that screening will detect cancer early. And if you detect cancer early, of course, you have a greater chance of being cured of cancer. That we know.

The problem with screening is that screening is full of deep statistical pitfalls. I’ll give you just a couple of them. First of all, when you screen someone, you get false positives and false negatives. False positives are things that, when you screen someone, it lights up, but in fact, you don’t have cancer.

A false negative is just the opposite. You screen someone. It says the test comes back all clean, all clear. But in fact, do have cancer. So screening tests have to navigate between false positives and false negatives.

But more importantly, a screening test will not tell you about the behavior of a cancer. So for instance, you might find a cancer in a screening test, but that cancer has already spread all over. And so you think that it’s localized. You perform invasive tests and invasive surgery– for instance, to remove the local cancer.

But it’s already spread. It’s too late. The horse has left the barn, as it were. And so that screening test has actually resulted in an operation, the consequences of operation, and physical harm, and potentially, risks associated with that surgery, but really done you no good because the cancer has already spread to outside the body.

So screening tests, what they’re trying to capture is what I call the mind of cancer, the behavior of cancer, what cancer will do. But screening tests don’t do that. They capture the body of cancer, not the mind of cancer. And by that I mean–

FLORA LICHTMAN: Not how it’s going to behave.

SIDDHARTHA MUKHERJEE: Exactly.

FLORA LICHTMAN: –but just where it is.

SIDDHARTHA MUKHERJEE: That’s exactly right. So there are many, many statistical pitfalls. So I encourage people to read through and be very thoughtful about screening tests. So that’s why I dedicated an entire chapter to this.

FLORA LICHTMAN: Yeah, I mean, it’s interesting. There was just a study this week out in JAMA estimating that over 60,000 lives would be saved over five years if we screened more widely for lung cancer. And I was thinking of you and your book and thinking that it must be hard to write about and wondering if you ever worry about people taking the wrong message away, that I was screening– I don’t need to get screened at all, because it really does feel like it’s case by case.

SIDDHARTHA MUKHERJEE: Well, the most important message that one can take from that chapter is that, if you screen people who are likely to have cancer, the chances that the test will actually be real is much higher. So in the case of lung cancer, the first group of people you want to screen are, for instance, 60-year-old and above long-term smokers. The chances that you find a lump in that population and that turns out to be cancer is much, much higher than if you screen a 20-year-old person who’s never smoked in their lives.

So the idea of using prior probability to guide screening trials is absolutely crucial. And we can do that now. We have genetics to guide us. We have behavioral studies to guide us. We can really screen in a much more thoughtful way than just sort of, as I said, screening a 20-year-old person with no risk factors for lung cancer and finding a lump and saying, oh, it’s cancer, let’s take it out, and having all the various toxicities associated with a false positive.

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FLORA LICHTMAN: OK, we have to take a quick break. But don’t go away, because when we come back, we’re going to ask Sid how he thinks about this problem of declining trust in science and how we get it back.

SIDDHARTHA MUKHERJEE: I think the problem is that a lot of science communication tries to simplify things and doesn’t respect people’s nuanced intelligences.

FLORA LICHTMAN: Don’t go away.

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As we’re talking about the nuances of talking and writing about science, which, of course, is near and dear to me, too, I’m curious for your thoughts on this issue we’re facing with trust in science declining.

SIDDHARTHA MUKHERJEE: Well, you’re raising an incredibly important issue, which is, even as we do better science and more nuanced science and send out, I would think, more nuanced messages about the discoveries that we’re making, trust in science is decreasing. The only way to combat that, I think, is to continue what you’re describing as nuanced writing about science and not give people false impressions, false hope, but really make them think through the process by which we communicate about science and be true to that idea.

Many of the chapters in this book have a lot of nuance to them. They describe, they walk you through why something is maybe a statistical mirage, even if you think that it’s a great invention. And that process of really respecting people’s intelligence, people’s–

FLORA LICHTMAN: Yes.

SIDDHARTHA MUKHERJEE: Really, really respecting it and taking that idea to heart and telling people what the excitement is, on one hand. But respecting their intelligence, I think, is the only thing, is the only antidote to the anti-science rhetoric that has spread all over. I think the problem is that a lot of science communication tries to simplify things and doesn’t respect people’s nuanced intelligences and then gets caught in its own trap, as it were, because you’re promising things that really don’t exist. I think really paying attention to the nuance is helpful. And eventually–

FLORA LICHTMAN: Trust your audience.

SIDDHARTHA MUKHERJEE: Trust and respect your audience because wherever that audience is, they are– I mean, and I found this across– when I do readings from the book or from my articles across the United States and across the world, there are people in all sorts of places who obviously care deeply about cancer. Cancer is not a red or blue disease. It is not a Black or white disease.

It is very much prevalent in every population. So the idea of trusting the audience and giving them all the nuances, I think, is extremely important. And that brings a level of trust back into the system.

FLORA LICHTMAN: One last one before we go– I know art is important to you. You were trained in classical singing as a kid. Does that have anything to do with your work? Is there an intersection?

SIDDHARTHA MUKHERJEE: I think it’s very important. In the book, you’ll see the juxtaposition of very deep scientific writing, I hope. And then I switch very quickly to, I would say, some of the poetics of writing about an illness that’s consumed our lives.

And one great example is that the very last page of the book is actually a poem. I’ll read it out very quickly. It’s a short poem from an Urdu poet. And I did the translation. “What I searched so earnestly for, I never found. But just in that searching, I found the whole universe unbound.”

And that poem is important because it captures the journey of a young oncologist becoming now an older oncologist–

FLORA LICHTMAN: [LAUGHS]

SIDDHARTHA MUKHERJEE: –and the humility that a lot of this has brought to my own life. That humility, combined with the excitement of all the new science, can only be described by this short poetic verse. And that’s why I think it’s very important to [LAUGHS] mishmash or crisscross the writing of deep science with an artistic quality.

FLORA LICHTMAN: Give us the poem one more time.

SIDDHARTHA MUKHERJEE: So it’s by Akhlaq Muhammad Khan, who wrote under the name Shahryar. “What I searched so earnestly for, I never found. But just in that searching, I found the whole universe unbound.”

FLORA LICHTMAN: Siddhartha Mukherjee is an oncologist and author of The Emperor of All Maladies, which turns 15 this winter. Sid, thanks for joining us.

SIDDHARTHA MUKHERJEE: Thank you very much.

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FLORA LICHTMAN: Today’s episode was produced by Kathleen Davis. I’m Flora Lichtman. Thanks for listening.

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