Mukherjee on Practicing Oncology, the Pulitzer, and His Next Book

; Siddhartha Mukherjee, MD, PhD


April 23, 2014

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Editor's Note:
In this segment of Medscape One-on-One, Eric J. Topol, MD, talks with Pulitzer Prize-winning author Siddhartha Mukherjee, MD, PhD, about his career as a writer, researcher, and practicing oncologist. Dr. Mukherjee is the author of The Emperor of All Maladies: A Biography of Cancer and is Assistant Professor of Medicine in the Department of Pathology and Cell Biology at Columbia University in New York.

Physician, Scientist, and Author: Siddhartha Mukherjee

Eric J. Topol, MD: Hello. I'm Eric Topol, and we are here for a Medscape One-on-One interview with one of the most interesting people in the world of medicine, and my friend, Dr. Sid Mukherjee from Columbia University. Sid, welcome.

Siddhartha Mukherjee, MD, PhD: Thank you. It's a pleasure being here.

Dr. Topol: You have been the consummate physician, scientist, and author, so it's great to have a chance to get to know you better. Before we get started, I thought we could review some background.

You were born in India and then went to Stanford for biology and worked with [biochemist and Nobel Prize winner] Paul Berg.

Dr. Mukherjee: I was born in New Delhi, India. I went to Stanford and studied biology. It was the late 1980s --1989 was the first year that I was at Stanford -- and I began to hear the term "recombinant DNA." I was an undergraduate student and I had taken my second biology class. I was fascinated by the idea of recombinant DNA. The wonderful thing about being an undergraduate is that you don't know what you don't know. I literally knocked on Paul Berg's office and said, "Would you consider having an undergraduate student in your laboratory?" He said yes.

Dr. Topol: Had he ever done that before?

Dr. Mukherjee: There had never been an undergraduate in Paul's lab. I think that was the first time. Both of us were totally shocked.

Dr. Topol: He's such a nice fellow.

Dr. Mukherjee: He is amazing and a great scholar, a great intellectual. He is deeply committed to scholarship, so he is a wonderful human being.

Dr. Topol: You quickly ascended to become a Rhodes Scholar at Oxford and got a PhD in immunology?

Dr. Mukherjee: Yes. I had the chance there to work with one of the great immunologists, Alan Townsend, who solved a deeply important question in immunology, which is, how is it that the immune system can recognize things that go wrong inside the cell? I used to call it the "outside-inside problem": How does something that lives outside the cell, such as the immune system, recognize something that lives inside the cell? There is a cell membrane barrier there. Alan solved that problem.

Dr. Topol: So you were dealing with the compartmentalization issue.

Dr. Mukherjee: We defined the idea of antigen processing and the idea that peptides are generated and picked up by molecules and presented on molecular trays to immune system cells -- just ask them to survey the interior contents of the cell. It's like a little sampling. Every cell is sending up a sampling of its innards. What is interesting is how relevant that has become for cancer.

Dr. Topol: You then migrated back to Harvard on the other coast, went to medical school, and did a Massachusetts General Hospital residency in hematology-oncology as well.

Dr. Mukherjee: Yes.

An Intellectual History of Cancer

Dr. Topol: So now you have finished your training. When along the way did you decide that you would like to write a book?

Dr. Mukherjee: The short version of the story is that I was a fellow and I was treating a patient. I had been interested in the broad world of ideas. I was reading a lot. (I had always read a lot.) I was asked by a cancer patient a very simple question. She said, "I'm willing to go on but I need to know what it is that I'm fighting." I was amazed by the idea that there had not been an intellectual history of one of the greatest families of illness in our history -- cancer. So I looked for myself and tried to find one, and when I couldn't find one, I decided that I would write one.

Dr. Topol: Had you had a history of writing?

Dr. Mukherjee: I had written a little bit, and I was keeping journals and things like that, but I'm a profoundly undisciplined writer.

Dr. Topol: I would never know that. When we first met, you told me, if I remember correctly, that it took 7 years to write the book.

Dr. Mukherjee: It took 6 years cover-to-cover, give or take. I thought it would take a year and it ended up taking 6 years.

Dr. Topol: Along the way, did you think you were going to stay with this thing? That's a pretty long commitment.

Dr. Mukherjee: There is something about learning medicine and science that really helped me. Medicine, science, and writing are stamina sports: You aren't judged by how fast you move, you are judged by the capacity to have stamina. It was very important for me to realize that. It's very important to teach undergraduate and graduate students that it is the length of scholarship that matters. Obviously, great discoveries stand by themselves, but those usually lie at the ends of long processes of scholarship.

Dr. Topol: You have all of this knowledge of molecular medicine but you are writing for laypeople. Is that a difficult transition?

Dr. Mukherjee: It is difficult if you make it difficult, and you can make it not difficult. The most important thing is to learn to respect the autonomy of your reader just as you learn to respect the autonomy of your patients -- in other words, if you imagine your readers as brilliant, thoughtful, and compassionate humans instead of abstracting them away. Think of what it is like to read. It is the same as your mentor physicians telling you to think about what it's like to be a patient.

I don't want to make an analogy between reader and patient; what I'm trying to say is that there is a profound level of communication that you learn from medicine that involves not oversimplifying topics but allowing the space of conversation, and then very complex ideas can be discussed. It is possible to do that. You just have to be confident that people will be able to rise to that place, and they will.

Publishing Emperor and Winning a Pulitzer

Dr. Topol: I am thinking about you having put this whole book together and sending it off to your editor, and then eventually going through the galleys and getting it published. Did you know this was going to have such an impact?

Dr. Mukherjee: The quick answer is no. When the book was first sent out into the world, it was 3 times its length -- it sat at 1800 pages. We had to pare that down to its current size. It was like wrestling a monster to the ground.

Dr. Topol: Can we ever read the outtakes?

Dr. Mukherjee: The Smithsonian has collected some of the outtakes. I have the extra passages. You can imagine that every page is littered with notes because I had a wonderful editor. I chose an editor who wasn't from the world of medicine. It was someone who was a wonderful writer and editor but could provide a different perspective. She would say, "This is unintelligible." To be edited by her, my condition was that she should be brutal and ruthless about her commentary. As they say in science, it's better to be criticized by your friends than to be criticized by your enemies.

Dr. Topol: It's very different because you are relying on an editor, unlike when you send in a peer-reviewed article and you have multiple reviewers.

Dr. Mukherjee: We invented a kind of peer-review system for this book. I said we should publish a galley copy, and we sent about 70 copies out and received comments back. It's amazing, the generosity with which people wrote comments back. These galleys were sent out to public health advocates and cancer researchers. [National Cancer Institute director] Harold Varmus was unbelievably generous. I can't tell you the level of commitment [people made], and it's because everyone thought that they were helping each other and me to do a public service, which is to dispel some important myths. Let's get a ground-level view. Let's get a sober view of where we are, what happens next, and where we're going.

Dr. Topol: This is amazing. I wasn't aware of that. Now, let's fast-forward. The book is out. How were you notified that you had won the Pulitzer Prize?

Dr. Mukherjee: It's one of those wonderful experiences. I had the luxury of meeting Paul Greengard, who won the Nobel Prize, and we did a taping in which we talked together. It's an exchange of moments in which you are told this unbelievable announcement. It's an interesting story. I had gone downtown to meet Tina Brown, who [at the time was] the editor of Newsweek. If you know Manhattan, my laboratory is on 168th Street, uptown. Tina's office at that time was way downtown. That's like traveling from Earth to Mars. For some reason, I had forgotten my appointment. I was uptown in my office and was in a foul mood. I said, "Oh my God, I have to travel." So I went downtown on the train. I had lunch with Tina and it was lovely. My mood was somewhat repaired by lunch. I left and then my cell phone went dead, so I was stranded downtown. I finally got to a place where I was able to charge my phone and I had 12 messages.

I thought, "This is very unusual. Something bizarre has happened." Someone had left a message saying "congratulations" because "the prizes had just been announced." I called up my wife and said, "This could be a prank, so can you please check for me?" She logged on to the Web, and of course when the Pulitzers are announced the Website goes down immediately. It's like the Nobel Prize Website, which inevitably crashes when the prizes are announced. So for 2 minutes I was on the phone and my wife was saying that the Website had crashed.

Dr. Topol: So they don't contact you directly?

Dr. Mukherjee: They contact you later. Eventually they call you. There is a waiting period during which you don't know.

Dr. Topol: This was a life-changer for you, I would imagine.

Dr. Mukherjee: Absolutely. How could it not be?

What Comes After a Pulitzer?

Dr. Topol: Now we are going to get into the physician-scientist part of your career. You have written your first book. You won the Pulitzer Prize in nonfiction. Where do you go from there? Are you going to continue writing?

Dr. Mukherjee: I'm writing a book on the history of and the future of the gene. In some ways, obviously, it has some similar elements to this book -- the social histories and the intellectual histories; they span time and space.

Dr. Topol: Do you weave patient stories in as well?

Dr. Mukherjee: Absolutely. I will leave a little bit of suspense, but there is a very personal story in the book. My book is subtitled "An Intimate History," which is part of my project. I'm interested in the structure of knowledge. How do we acquire it? Where does it break down? What are its consequences? What are the cultures that allow us to possess it and to grasp it, and where is it lost? How do we delude ourselves with it?

Dr. Topol: When is it due to be published?

Dr. Mukherjee: In 2015.

Dr. Topol: So this one hasn't taken 6 years?

Dr. Mukherjee: Well, the time adds up.

Dr. Topol: You practice as an oncologist. How do you balance that with being in the lab?

Dr. Mukherjee: My practice is very limited. It is focused on preleukemic diseases called myelodysplastic syndromes (MDS). They are complex diseases, and I like the complexity. But one way that I manage is by having a very tight intellectual focus in my practice. Essentially, I see only patients with MDS. Twice a year I will go to the wards and do a very general practice. I call it my refresher course. It reminds me of where we are more globally. That's when I see the entire spectrum of patients: breast cancer, lung cancer, ovarian cancer, everything. For me it's an experience that grounds me and it's very important. I keep that. It's a very precious time for me.

Dr. Topol: In the lab you are studying hematopoietic stem cells to understand MDS.

Dr. Mukherjee: That's right. Our focus in the laboratory is to try to link steps between stem cells and cancer, focusing particularly on blood cancers because we know those stem cells better than any other cell.

Dr. Topol: There is almost too much overlap between stem cells and cancer.

Dr. Mukherjee: One thought is that cancer arises by co-opting or parasitizing, or pulling out from physiology things that have been maintained in stem cell physiology to make it more concrete. Self-renewal is an idea that is very much part of a stem cell, but if you think about it in a malignant variation, we now think that some cancers have a variant of self-renewal. They are malignant self-renewing cells.

Dr. Topol: I understand that your wife is an artist. What kind of artist is she?

Dr. Mukherjee: My wife does very conceptual, large installation work. Sometimes she does smaller works too. She makes works that are about memory, often using found objects. She inherits a tradition from Rauschenberg and others of trying to understand how we manipulate space and how we ascribe value to things.

Dr. Topol: That's fantastic. You are a young guy. You are only 44?

Dr. Mukherjee: Yes. I look younger than I am.

Ken Burns Takes on Cancer

Dr. Topol: You have decades ahead in your career. What would you like to achieve?

Dr. Mukherjee: I am really interested in the structure of knowledge and in finding that out as best as I can in various diverse ways. People often say, "How can you wear so many hats?" I don't see myself wearing many hats. I think I wear only one hat. My interest is in the lineage of knowledge and in discovery, in skepticism, and in being able to integrate all of that with what I call human knowledge. How do we understand more about each other from the way we have discovered things about ourselves in the past? That is my bigger project. Ken Burns is doing a film on The Emperor of All Maladies.

Dr. Topol: I did hear about that. When will it be out?

Dr. Mukherjee: In 2015. It's an advanced production, a 6-hour film. It is the next flagship, Ken Burns' project. He will finish Vietnam this year and then move on to what I think is called Cancer. It was announced 2 or 3 months ago. We had begun filming a while ago.

Dr. Topol: Is it basically inspired by the book but not with actual scenarios from it?

Dr. Mukherjee: Both. I'm a co-producer on the film. It follows the structure of the book, but it has a much larger format. We have been able to pour even more resources into very deep archival material. Barak Goodman is taking the frontline in putting this film together, with Chris Durrance and several others. It is an incredible production.

Dr. Topol: It sounds fantastic.

Dr. Mukherjee: Working with Ken made me understand that there is a similarity of method; he is also interested in structuring the archeology of all of these events. It's been an incredible experience.

Dr. Topol: Would you ever have thought that you would get into something like that?

Dr. Mukherjee: No. With Ken it was a cold phone call. I was sitting in my office and picked up the phone. It reminds you that there still is something very persuasive in talking one-on-one and making decisions. For me it was instinctual. I had watched Civil War and loved it. I told Ken that it was a great public service, and I hope that this will be another great public service.

Dr. Topol: There is no question about that. When you are not in the lab or with patients, and when you are not writing, what else do you do?

Dr. Mukherjee: That takes up most of my time.

Dr. Topol: Do you like to read other stuff, such as fiction or nonfiction?

Dr. Mukherjee: I mainly read fiction. To write, you have to read. The basic structure of storytelling derives from fiction. I don't think it's a coincidence that among the greatest fiction writers are physicians -- Chekhov being high on that list. I have made a strong argument that one of the reasons that Chekhov originated the short story had to do with his life in medicine.

Dr. Topol: You have had an amazing career in a short span of time. We wish you continued great success. We have this series, "the Dos Equis of most interesting people in the world of medicine." You fit that to a T. It's wonderful to get to know you better. For all the folks at Medscape, thanks so much for being with us.

Dr. Mukherjee: It was a pleasure. Thank you for this program.

Dr. Topol: Thank you for joining us for this Medscape One-on-One. We will continue our series with some of the most interesting people in the world of medicine.


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