08-05-2025
The C-Word: Dr. Siddhartha Mukherjee wrote the book on cancer
The book shows that if there's one constant in cancer research, it's that it's always changing. On this episode of 'The C-Word: Stories of Cancer,' host Shirley Leung talks to Mukherjee about how his time living and working in Boston changed him as a doctor. They discuss the hopeful progress we've made in curing cancer — and the challenges that persist.
The following is a lightly edited transcript of the May 8 episode of the 'Say More' podcast.
Shirley Leung:
Welcome to 'Say More' from Boston Globe Opinion. I'm Shirley Leung. This is episode 2 of our series, 'The C-Word: Stories of Cancer.'
Today we're talking to the man who wrote
the
book on cancer.
Siddhartha Mukherjee is the author of 'The Emperor of All Maladies.' It covers the long history of this disease, why it haunts us, why it's so hard to beat, and why there's hope.
Siddhartha, who goes by Sid, learned everything he knows about cancer while working in Boston as a young doctor. I traveled to New York to meet him at his lab at Columbia University Medical Center. I asked him about the title of his book and why, when it comes to disease, cancer is the emperor.
Siddhartha Mukherjee:
At the end of the book, I realized that this was a disease that had occupied our brains and minds and bodies for centuries in a way that really no disease had. This was the thing that we had battled for so many years and have continued to battle.
In the 1950s, people would say, 'What do you wanna be when you grow up?' And people would say, 'I wanna be a rocket scientist.' In the 1960s and 1970s, if you asked the same question to a young man or woman, they would say, 'I want to be a cancer doctor.'
There's a spirit in which this has reigned so large over our imagination that it seemed like of all illnesses, this was the emperor, the most important and perhaps the one that we need to defeat.
Leung:
It's been 15 years since your book has been out, and many of the meaty chapters in the book were about research breakthroughs and lifesaving treatments in the late 1990s and early 2000s. Are those chapters out of date now?
Mukherjee:
We'll be glad to know that in September we're publishing an evergreen update with five new chapters. I'm writing them as we speak, and directly after this interview, I'm going to my publisher to start putting them down on real paper, editing them and so forth.
So the book will become evergreen again in September. There's a new release called 'The Emperor of Maladies: Part 2,' which is, of course, a release of the new chapters with all the updates from that.
Leung:
When we start to read those five chapters, will it show how fast moving the research is or what will it show?
Mukherjee:
It'll show a mix of things. It'll show the disappointments. 'The Emperor of All Maladies' was not written as a kind of a triumphalist history.
It was written as a kind of process of science. And the process of science involves defeats, it involves disappointments, it involves griefs. It'll show all of that.
Leung:
When you finished your book 15 years ago, did you foresee laying out these five new chapters? Was that a surprise to you or did you see that coming?
Mukherjee:
Some of it is a surprise, some of it was in process.
Immunological therapy for melanoma and other cancers was in its early infancy. Some of the new chapters on breast cancer are amazing. Some of the new chapters on other cancers are just really different. So it's a mix. Some of these were early in development, some of these were late in development, but all of these are great successes, great surprises, and I think there's no way to describe them aside from the fact that we are fortunate to have them.
We are fortunate to have these researchers dedicate their lives, and we're fortunate to have patients enroll in trials to get these treatments into real life.
Leung:
There's been a lot written about younger people getting cancer. Usually you think of this as a disease of very old people, right? But now people are getting cancer in their 20s, 30s, and 40s. I know people in my own life who had cancer in their 40s that have passed away.
At the same time, there are all these new treatments that you've just laid out. I'd never heard this term before, but I love it. This idea of the Red Queen hypothesis. It's this idea about an evolutionary arms race where science has to constantly keep up just to stay in the same place.
Talk more about that.
Mukherjee:
The idea of the Red Queen is that we never conquer a disease. We are always in equilibrium with the disease. It's a kind of game of chess. The disease plays its game, we play a game, and we figure out how to resolve these two games.
A lot of the young cancers that we're diagnosing are because of better diagnostic technologies. But that's not all, habits have changed, people have changed, carcinogens may have changed.
Overall, if you look at the data, the rate of cancer deaths in the United States has been decreasing pretty consistently overall. The decrease is important and striking.
Over the last 15 to 20 years, it's decreased almost from, I'll just give you a kind of rough number, 150 per a 100,000 to 110 per a 100,000. That's a big number. That's a big, big, big, big, big number
Some cancers are changing, some are on the rise, some are on the fall. But overall, the effect has been positive, it's been enormous, and it's been underestimated and under-reported.
Leung:
So would you say we're winning this medical chess game then?
Mukherjee:
Winning is a complicated word. Your definition of winning might not be my definition of winning.
But are we moving in the right direction? Yes, we are moving in the positive direction for many of the common cancers. Some we're still struggling with. Pancreatic cancer, we're struggling with. Some are increasing, and we don't know why. But overall, the direction is not negative, but positive.
Leung:
So one of the things you're really good at is explaining to non-doctors why cancer is so hard to treat, compared to other diseases. So what makes it so tricky?
Mukherjee:
One of the things that's very tricky about cancer is that cancer arises from your own cells. It's not an external invader. It's not like a bacterial infection. It's not like a viral infection.
All the viruses can cause cancer, but really, ultimately, it's your own cell that's gone wrong. And the differences between a cancer cell and a normal growing cell are pretty subtle. One of the things that we struggled with is, 'How do we kill a cancer cell without killing a normal cell?' Because the differences are so subtle.
So what are the distinctions? How do we find the particular vulnerabilities of a cancer cell that are not the same as the other cell?
When you think about standard chemotherapy, not modern chemotherapy, it makes you think about killing all growing cells. You lose your hair, you lose your skin, you lose your immune system, things that grow.
That's because we are targeting growth in general, but growth is important for every cell. Growth is important for our bodies to maintain ourselves.
The real trick in cancer is to be exactly discriminating between the normal and the cancer cell. That's a very hard trick because they're very closely related to each other. One arises from the other because of mutations, but also one arises because of subtle mutations. It's not like the whole cell turns into a monster.
It's very particular that cancer cells grow while normal cells don't grow.
Leung:
I'm so glad you brought that up, because I think that's one of the reasons why it makes cancer so scary is because it comes within ourselves. We are the enemy.
So you made a distinction between modern chemotherapy and standard chemotherapy. What does that mean?
Mukherjee:
More and more standard chemotherapy was directed at saying, 'Let's kill all growing cells.' If there's collateral damage to normal growth, it's just collateral damage. That's why chemotherapy was so toxic.
Modern chemotherapy is about trying to find out what is precisely different about cancerous growth versus malignant growth versus normal growth. We found that there are different cancer cells that use different metabolic pathways. They use different ways of growing.
That's why with modern chemotherapy, we want to think it's less toxic, it's more directed, it's more targeted, it's more personalized, and has been, generally speaking, less poisonous than the chemotherapy devised in the 1950s and 1960s.
Leung:
It used to be you think of someone on chemotherapy, they lost their hair, they lost weight. But now people go through chemotherapy and they have their hair.
Mukherjee:
Hair is just the beginning of it.
People with myeloma are living tens of years, twenties of years and surviving. They're going to work, they're being members of society, and they're enjoying their children and grandchildren in a way that they weren't before.
And that's, again, because we found these Achilles' heels, and these Achilles' heels are very important because they're exactly that.
They are ways in which cancer cells resist the normal controls of growth. They are able to grow despite those normal controls.
Leung:
It seems like it's huge for quality of life, for patients.
Mukherjee:
Quality of life, but ultimately survival.
Leung:
I want to bring our conversation to Boston. You went to Harvard Medical School, you did your residency at Massachusetts General Hospital. I think you did a fellowship at Dana-Farber Cancer Institute, as well. You really spent your formative years in Boston before heading to Columbia.
So what do you think about your time back in Boston? And what did you learn about cancer being there?
Mukherjee:
I learned everything about cancer being there.
It was my formative years. Those were the years in which I learned to understand cancer. I learned to understand the mutations. I learned to understand the effects that cancer has on cells. But I think most importantly, I learned to understand the effect that cancers have on people's lives, through the patients I saw.
I saw hundreds of patients. I saw patients from every ilk of life. They shared this same drive to live, the same drive to want to live, but they shared a kind of dignity that was very important.
My time in Boston taught me that the dignity of a patient is just as important as a patient's life, and the dignity of a patient is something that's negotiated. I often teach my students that cancer therapy is not an absolute, it's a negotiation.
You have to ask a patient, 'What do you want out of this? How far do you want to push?' Because you could push very far.
'Where do you want your life to be? What do you want your life to look like? How far are you willing to participate in a clinical trial or in deeper segments of cancer therapy?'
All of that I learned in Boston. And I think that idea was really initiated for me in Boston, and for the world in Boston, because Boston's one of the centers of cancer biology and cancer therapy.
Leung:
Can you share one story about a patient, maybe Carla from Ipswich?
Mukherjee:
Yeah, Carla. That's a very important story.
Carla was an adult with acute lymphoblastic leukemia. I met her early on in my fellowship. She had young children then and she wanted them to go to college. For some reason she wanted them to go to Princeton University.
I was like, 'Carla, we'll get your kids to Princeton. I mean, the kids will get in themselves, but Carla, you'll get to see them in college.'
We think about cancer therapy in so many different ways. We think of cancer therapy as medicines, but cancer therapy is psychological. Unlike virtually any other discipline, a cardiologist becomes your psychotherapist. They become your colleague, they become your friend. He or she becomes the person you talk the most intimately about your life with.
And Carla lived. We cured her.
Leung:
You didn't think she would live, though.
Mukherjee:
I didn't think she would live.
Leung:
What happened?
Mukherjee:
No one knows what happened. It was some combination of genetics and therapy and her persistence to come to every appointment.
Leung:
In the horrible Boston traffic, right?
Mukherjee:
In the horrible Boston traffic
, i
n the middle of the winter when the snow was terrible.
But she lived and she got to see her children go to college. It was an enormous victory.
Leung:
How did those conversations with Carla or others go? Did any of it surprise you? Did any of it change your perspective as a doctor?
Mukherjee:
Every conversation is a surprise. Some people say, 'Listen, I'm done. I've had enough.'
And you might not expect it. Some people might say in the beginning that they want to be done and they all of a sudden change their mind and say, 'I want to continue.'
So in every conversation you have to negotiate it. You can say to them, 'You're so close, are you sure?'
And they might say, 'Yes, I'm sure.' And then you say, 'It's your own game. It's a chess match.' You have to be certain, but you can't be too certain because you have to tell the truth.
There's a very beautiful line from Emily Dickinson, which says, 'Tell all the truth, but tell it slant.'
And that really means that when you encounter a cancer patient, you always tell the truth. You always tell the truth, but sometimes you have to tell it slant. And by slant, Dickinson means tell it in a way that it can be absorbed, in a way that it's not final.
Americans deal with finalities. 'Here is a number. Your survival is x percent.' But that's not true. Your survival is a very complex number that depends on your genetics, your environment, your capacity to tolerate a trial. And so telling the truth's slant, it's an incredible piece of wisdom by Dickinson.
Leung:
My background is in business and finance reporting, so I was really fascinated to learn about the history of cancer philanthropy and fundraising in Boston. It sounds like we probably pioneered it, right?
Mukherjee:
Boston was certainly one of the places that pioneered it, along with Sidney Farber and Mary Lasker, who would be two famous figures.
Leung:
I think about our main cancer center, Dana-Farber, named after Dr. Sidney Farber, who's the father of modern chemotherapy. He really invented this idea of cancer philanthropy, which is so fascinating in your book. How important was he and Lasker in the way we think about cancer now?
Mukherjee:
Crucially important. Farber and Lasker's partnership lasted a lifetime.
It was truly important that they figured out that the only way to beat cancer was not just through private engagement with patients, but through a larger public engagement.
Leung:
And Mary Lasker was the marketer and fundraiser, right?
Mukherjee:
She was a marketer and fundraiser. She was amazing at it. She went to Congress, she went to patients. She was a patient advocate, she was a political advocate. She was everything rolled into one and I think that she was just a remarkable figure.
She moved it from a disease that was in the backdrop. She came out in front and said, 'We need to talk about this disease. We need to talk about it politically. We need to talk about it financially. We need to talk about it as a budget.'
To really think about the idea that this was something special, that patients were suffering, they were underserved, and that they would be better served by a special institute for themselves. That was what Mary Lasker did.
She really mobilized Congress and ultimately was responsible for the drafting of the idea of the war on cancer. Congress political entities don't declare wars on diseases, they unfortunately declare wars on nations. But it would be so wonderful if we declared wars on diseases and Mary Lasker was the first person to really coalesce on the idea that the job of Congress was to declare war on diseases, war on things that haunted human beings.
Leung:
Going forward, what would it take for Boston to continue to be an important place for cancer research?
Mukherjee:
I think the important thing is to attract talent. And talent comes from different places these days. In the United States, talent has almost always come from a mixture of local talent and immigration.
Ecosystems form. Ecosystems are really important because you and I talk to each other one day in the common dining space of an institute, and I say to myself, 'Oh my God, that was a really smart idea. How can I apply that to cancer?'
These ecosystems are networks. If anything, the last 10 years have demonstrated the importance of networks in all of social sciences.
Boston was, and still to some extent is, one of the magnets of world talent. If you are a kid in Kenya and you want to cure cancer, you say to yourself, 'How can I get myself to the Dana-Farber Cancer Institute?'
You drive yourself there, and then you meet other people who have the same vision and then you find that there are funds available for you to be able to do that research. That's what magnetism is, and if you lose that magnetism, I think you lose everything.
Leung:
Your book lays out how important federal funding was to all the treatments we're seeing now with breast cancer and leukemia. Spell it out a little bit more for people who haven't read your book.
Mukherjee:
Sometimes I'm just writing a piece about Covid vaccines, and it's the Moderna vaccine.
But it's not really the Moderna vaccine, it's the National Institute of Health (NIH) vaccine. The NIH is the one that supported years and years of mRNA research by Drew Weissman and Katalin Kariko to create what would eventually become the Moderna vaccine.
Over and over again, the idea of science funding translated into human research has turned out to be enormously valuable. Hundreds of thousands, if not millions of people have been saved by just the drug Herceptin. Think of the number of people in your own life. Each of us can name a person, and think of the network effect.
A mother who would've died at age 38, who now is alive at age 52. Those years of her life were given to bringing up her child. It's just impossible for me to enumerate. People have done numbers on this and showed that every dollar spent on the NIH converts into tens, if not hundreds of dollars, saved in human capital.
I think we underestimate it. Slashing that is just the worst idea on the planet.
Leung:
Can private philanthropy make up the difference?
Mukherjee:
No, no, no, it cannot. Private philanthropy is an adjunct. The central forces have to come from federal sources.
Leung:
Why?
Mukherjee:
It's just because private philanthropy historically follows the direction of what we are thinking from the center. That's the seed. It's the spark that lights the fire. And without that fire, we're really done for.
Leung:
So one of the big takeaways of your book is the need to reimagine how we think about cancer. And how that in itself would be a victory, if we could reimagine how we think about cancer. That cancer isn't an imminent death. That it's not about finding a universal cure, but that the disease can be managed.
So talk to me more about that.
Mukherjee:
I think of cancer more and more as a journey. In some cases, the journey's abruptly terminated, which is sad, but in many, many cases, the journey continues.
While the journey continues, we've given back people real lives. They're not just obsessed with the journey. It's not like they're in the hospital all the time. They're going back to their homes, they're going back to their real lives and then coming to the hospital for their treatment.
So, I think that's a real change.
Leung:
What do you think people get wrong about cancer in our society and what is the one thing you want people to understand about the disease?
Mukherjee:
I think they need to understand it's not a death sentence. It is one word in a sentence that continues for a very, very long time.
It's one word in a paragraph and that paragraph continues for a very long time for different cancers. I don't want to give people false hope. Some cancers are deadly, but I also want to give people the idea that they continue their lives beyond cancer, and I think that that's what's missing.
Leung:
Siddhartha Mukherjee is a physician and assistant professor of medicine and researcher at Columbia University. He's also the author of the 'Emperor of All Maladies' and the 'Emperor of All Maladies: Part 2,' along with other award-winning books on medicine.
Listen to more 'Say More' episodes at
Kara Mihm of the Globe staff contributed to this report.
Shirley Leung is a Business columnist. She can be reached at
