Author and Oncologist Dr. Siddhartha Mukherjee on the History of Cancer

“Medicine is storytelling,” writes acclaimed cancer specialist and now bestselling medical historian Dr. Siddhartha Mukherjee, author of The Emperor of Maladies: A Biography of Cancer, named one of the top ten books of 2010 by The New York Times, among others.

I began my interview with the very busy Dr. Mukherjee by telling my cancer story. I was diagnosed with stage III colon cancer in 1996 after I finally agreed to a dreaded colonoscopy. My mom was diagnosed with colon cancer a few months earlier and she and my wife Betsy, a nurse by training, urged me repeatedly to get a colonoscopy. I didn’t want the test, and argued that my physicals and blood tests were normal, I was under fifty, and I never had digestive problems. But the storm of solicitude was too much, and I finally relented.

The colonoscopy itself was not painful or dreadful, but it revealed a tennis-ball size tumor of the colon in the same location as my mom’s tumor. My doctor was stunned. He said the tumor could have caused a blockage—probably curtains for me—at any time. I soon had surgery followed by a year of chemotherapy.

Fortunately, I’ve had no cancer problems since then. After treatment, I went on to testify before the state legislature and talk with groups on the importance of early screening.

Dr. Mukherjee graciously congratulated me on my recovery. He related my storytelling to his The Emperor of Maladies, a collection of stories from the four-thousand-year recorded history of cancer interspersed with accounts of his work in medicine and the experiences of his patients:

You started our conversation with a story that contains in it a very personal dimension and captures a history of ideas and something cultural, and something political as you were testifying in Washington state about your screening and your colonoscopy. In the process of four or five minutes, you narrated a story that captures not just your history but also a political and cultural history. It’s a reminder that medicine is constantly trying to capture stories and tell stories back. These are very intense stories because they have to do with culture, life, death, legacy, survival. Medicine is never far away, and if it strays far away, it needs to be brought back.

Dr. Mukherjee’s book of history and interlinked stories has been praised for its compulsive readability and surprising hopefulness. The book earned rare starred reviews from Booklist and Publisher’s Weekly. The PW reviewer enthused: “Mukherjee's debut book is a sweeping epic of obsession, brilliant researchers, dramatic new treatments, euphoric success and tragic failure, and the relentless battle by scientists and patients alike against an equally relentless, wily, and elusive enemy.” And Steven Shapin wrote in The New Yorker: "It’s hard to think of many books for a general audience that have rendered any area of modern science and technology with such intelligence, accessibility, and compassion. The Emperor of All Maladies is an extraordinary achievement.”

Dr. Mukherjee is an assistant professor of medicine at Columbia University and a staff cancer physician at Columbia University Medical Center. He was a Rhodes scholar, and he holds degrees from Stanford University, University of Oxford, and Harvard Medical School. He lives in New York with his wife and daughters.
Dr. Mukherjee spoke with me by phone after struggling free of a New York City traffic jam.

Lindley: What inspired you to write a history of cancer?

Dr. Mukherjee: The inspiration came from patients. When I was training in cancer medicine in Boston, this is a question I got asked over and over again: What is the history of cancer? Cancer patients were interested in defining their history. In particular, one woman I was treating for stomach cancer said I’m willing to go on with my treatment but I need to know what it is that I’m fighting.

It was amazing to me that, although this disease is enveloping more of our lives and we’ve poured literally our best scientific and public resources at it, there was no attempt to write this story. It seemed to me that we needed to find a way to describe to my patients where we were in cancer and what happens next. Just acknowledging that cancer is not one disease but many diseases, and yet common biological and cultural principles connect all these diseases, so it was surprising there was no comprehensive attempt to write a story of where we are now, what happens next. So this history was to answer a patient’s questions.

Lindley:  You call your book a biography of cancer, which distinguishes it from a strict history of medicine.

Dr. Mukherjee:  Exactly. When I started the book, I literally titled it “A History of Cancer,” but as I was writing it, I felt as if the word history was just too inert to describe not only my experiences, but also the experiences of patients. I was looking for an alternative description that would capture what I was trying to achieve. Also, I was drawing a portrait over time of a family of diseases, a very heterogeneous disease, looked at from so many different viewpoints: someone considering it in 2500 BC and someone else looking at the same entity a hundred years or four hundred years later and picking up different elements of that portrait. Drawing a portrait over time is of course a biography. Therefore, I switched to the word “biography” of cancer.

Lindley: What is cancer?

Dr. Mukherjee: Cancer is not one disease, but a family of diseases. They share a common feature: a cell that has lost control of cell division and is dividing abnormally. Cancer is not just that; there are many more features. Cancer invades the immune system and metastasizes. At its essence, cancer is an abnormal growth of cells typically originating in a single cell.

Lindley: How does cancer kill us?

Dr. Mukherjee: Different cancers kill for different reasons. Typically, cancers kill by virtue of metastasis by invading organs, growing in spaces where they’re not supposed to grow, and taking over and destroying the function of organs. That’s not the only way. Cancers can kill us in a variety of different ways. For example, leukemias become lethal often when they wipe out normal growth of bone marrow and take over the bone marrow much like an invader may take over the growth of any state. By contrast, brain tumors don’t kill by virtue of metastasis, but kill patients because they grow in that space and destroy brain tissue around it. Every tumor has a different pathology of killing, but the fundamental feature is the same: the abnormal growth of cells.

Lindley: The book goes back more than four thousand years, yet cancer is thought of as a disease of modern civilization.

Dr. Mukherjee: Cancer is thought of as a disease of modernity partly because the rates of cancer are increasing over time, [because] our population is aging overall and cancer is an age-related disease. There are other reasons that the cancer rate is rising. For instance, an increase in tobacco smoking in the past caused an increase in lung and possibly esophageal cancer. But one of the main reasons is that the population is aging over all. Put some numbers on it: the average life expectancy in the United States in 1900 was forty or fifty-odd years. That has increased to seventy-odd years in the matter of a century. That is exactly when cancer [usually] strikes, in the decades from fifty to seventy. Much of the increase in cancer is related to the aging of the population, and that is part of the reason that cancer is associated with modern times.

Lindley: Are cancer rates in the developed world higher than in other regions?

Dr. Mukherjee: It’s a complicated question partly because people live longer and aren’t dying of other diseases. One can’t do a comparison across the board like that. Some cancers are more common in the developed world, particularly age-related cancers. Other cancers are less common in the developed. For example, liver cancer is endemic in parts of Asia partly because we’re now vaccinating for hepatitis A and B. Similarly, cervical cancer can be vaccinated against, so there is a predominance of this in the non-developed world, so there’s a disparity there.

Lindley: What was the understanding of cancer before the nineteenth century, before more recent treatments such as Dr. William Stewart Halsted’s radical mastectomies of the late 1800s?

Dr. Mukherjee: There have been several different understandings. [Roman physician] Galen posited a theory that the body was made up four fluids: yellow bile, black bile, phlegm and blood. Cancer was an excess of black bile. Therefore, Galen argued that cancer was a systemic disease, a disease that the entire body was involved with. This theory persisted for a long time.

It was only in the early nineteenth century, when surgery became more prominent and advanced, that surgeons began to take out local forms of cancer and thereby cure patients. Halsted inherited the idea that if some surgery is good, more must be better, then took it to its logical conclusion. He performed increasingly aggressive variations of surgery in order to cure cancer patients completely, and he called it radical mastectomy.

Lindley: The main treatments that developed from that time were “cutting” or surgery, then “burning” or radiation, and then “poisoning” or chemotherapy. Is that a way of making sense of the progression of treatment?

Dr. Mukherjee: Yes, although that is changing dramatically. First, these variations of cutting, burning and poisoning have often worked together. For example, with breast cancer today, a woman with stage two or three breast cancer is treated with surgery followed by chemotherapy followed by radiation. So all three are used together.

But we’re looking at an era in which surgery is the mainstay of much of cancer therapy, and also an era where we’re finding new medicines that are not so poisonous, which selectively poison only the cancer cells and spare [healthy cells] with these so-called targeted therapies. These therapies have been around for a while. Indeed, the very first targeted therapies were used in thyroid cancer and soon after in breast cancer since the 1940s and 1950s. So these therapies are actually a fourth part of the armamentarium in which, instead of cutting or burning or poisoning generally, they specifically attack cancer cells and spare normal cells. That’s the direction cancer treatment is turning.

Lindley: You point out that the pioneering physicians used new treatments very aggressively on patients, but you have compassion for these physicians.

Dr. Mukherjee: I do, but I certainly have more compassion for the patients who bore the brunt of these therapies. It’s important to realize that the doctor’s have—and certainly patients have it—this load of urgency. You can’t tell a patient come back in five years once I’ve figured out how to treat breast cancer. I’ll treat you then. Patients need treatment right there and then. So doctors have to balance the current state of knowledge against the current lack of knowledge and act in the moment.

Scientific researchers have the luxury of being in the laboratory where they can say I haven’t solved the problem; I’ll get back to you. This is not a luxury we have in medicine, so I have to be sympathetic to the urges of doctors to cure this disease. They were fighting a disease that was mysterious and deadly. In the face of that, the idea that they would so quickly reach for the most aggressive tools that they had is not surprising. On the other hand, it speaks to the arrogance of medicine, and the fact that medicine is constantly trying to overreach its boundaries.

Lindley: You display a great empathy for your patients and bring them to center stage in your book. What have you learned from your patients?

Dr. Mukherjee: There are so many things. One common thread that stitches the whole story together is the idea that patients are incredibly inventive. They have surprising resilience, and they carry forward resourcefulness that will amaze and surprise you. The book is a reminder of that.

Lindley: And you were actively treating patients as you wrote the book. Can you talk about your writing and research for the book, and how in particular you conducted historical research?

Dr. Mukherjee: I was doing a lot of archival research. For instance, all of [cancer research fundraiser and advocate] Mary Lasker’s letter and files are at Columbia [University].

The way I found the [pediatric leukemia] patient Robert Sandler—who the book is dedicated to—is an interesting example. I only knew his initials “R.S.,” and I didn’t know anything more about him from [cancer researcher] Sidney Farber’s papers. I was looking for this child who was treated for leukemia in 1948, and I knew he had a twin, but I didn’t know anything else about him. I began to send out requests on this child through list serves. I knew of the twin, and I said if your twin was diagnosed with leukemia in 1948, please contact me. But I got no replies.

I went to India and, it turned out, I met a biographer and historian who visited Boston in the 1950s and was interested in leukemia, and he lived two doors from my house in India. He had kept a roster of all the patients Sidney Farber had treated for leukemia, and there in the box was a picture of Robert Sandler. So six thousand miles away from Boston, where I expected to find this child, I found him in India.

Then, I came back to Boston with his name, and I could trace back using the Boston phone directory and death records. I found his parents’ names, his house, and additional records on him, and finally could establish who the child was.

That’s very important because it’s a reminder of how complex researching a book is. You find history in the most unlikely of places including archives and also primary interviews, phonebooks, address books.

In the Boston Public Library, I found the boy’s picture in the Boston Herald. And a week after the book was published, Robert Sandler’s twin found the book and called me. He was crying on the phone [saying] his brother had died three months after therapy sixty years ago, and my brother vanished from my life. Yet this book brought back that child and, in fact, is dedicated to him. And the mother is still alive and I was able to speak to her and the brother.

That’s what’s amazing—the kind of ripples that a book like this can cause. They involve all kinds of research—there’s no single kind. And you’ll notice in the book, there’s no single voice of research. Sometimes it’s historical or it’s personal, or sometimes it’s more cultural or literary. It was very important to me to use a variety of voices to understand the historical scope of cancer.

Lindley: Your writing is compelling and exceptional for clarity on very complex issues. What are your influences as a writer and historian of medicine?

Dr. Mukherjee: There are people I leaned to formally in figuring out how this book was written. Richard Rhodes, The Making of the Atomic Bomb, was very influential. Susan Sontag’s book, Illness as Metaphor was also very influential and so were Alexander Solzhenitsyn’s Cancer Ward, and Tony Judt’s Postwar. And also Primo Levi’s Survival in Auschwitz where he takes a small story and tells a much larger, deeper story about humanity and about a moment. It was very, very influential to me, and I read that book several times while I was writing this book. So there are a diversity of influences, some of which are not obvious. The relationship between this book and Primo Levi’s book is not obvious, but if you look at its craft and effect on my mental surfaces, you find those influences very actively.

Lindley: Did you dream of being a doctor when you were a child?

Dr. Mukherjee: I did, but I didn’t know what kind of doctor. I was intrigued by the sciences as a child and sensed that I wanted to study something in that arena but how exactly I would intersect with the sciences was a question. I imagined I would study medicine, but only much later. I first studied cell biology and only later became interested in medicine, unlike many people who begin in medicine and eventually gravitate toward cellular biology. My journey happened in reverse. I first finished my Ph.D., and only then did my M.D. That probably has something to do with the way the book is written but also the way I approached this whole field.

Lindley: What drew you to study and treat cancer? Did you have personal experiences?

Dr. Mukherjee: I did. One of my early experiences was my high school English teacher died of breast cancer. I had a particular love of English, and I had a very strong memory of that moment. Since then, many family members have had cancer, and it’s not a surprising phenomenon any more. Cancer is literally taking over our lives as we age, so my family also has experienced cancer in its various forms. Those are certainly active influences on my life and cancer. And also, as I told you, I first trained as a scientist and only then came to cancer medicine so I looked at cancer through a microscope before I treated cancer patients.

Lindley: And you grew up in India?

Dr. Mukherjee: I grew up in Delhi at a time when India was steeped in respect for science and medicine. That was very important to me, though my interests were wide-ranging in the humanities and in the sciences.

I continue to be struck by the level of respect that the sciences command in India. That sense of respect is incredible, and it pays itself off in very good science education. We know the United States is lagging in the best science education, which is really unfortunate [and] will have ramifications in arenas like our fight against cancer. We really need to put the best of our resources into this and if we can’t, that’s a real tragedy.

Lindley: What reforms would you like to see?

Dr. Mukherjee: I would like to see powerful, strong scientific education emerging in this country.

Also, as I point out in my book, the pediatric trials were so successful because nearly every child in the 1940s and 1950s who was treated, was enrolled in a clinical trial [and] with every trial we learned something. It seems to me that we should be encouraging people to participate in clinical trials.

Lindley: Do you have thoughts on improving access to health care?

Dr. Mukherjee: I have many thoughts. With cancer in particular, there is an incredible disparity between access to responsive cancer medicine. You can invent new therapies for cancer, but if you can’t deliver those properly, then the invention comes to naught. The invention is only as useful as getting that invention to real patients in real time. So we need to improve our network of health care delivery, and make important, therapeutically successful strategies available to all patients.

Lindley: Can you discuss what you’ve learned about prevention of cancer?

Dr. Mukherjee: One of the most exciting things in cancer medicine these days is an integrated approach to prevention in which we’re taking the molecular understanding of cancer and converting that understanding into mechanisms to prevent cancer better. So rather than just taking an epidemiological approach with controlled studies to prevention—which is very powerful, the integration of molecular approaches and cancer biology interventions will be very crucial.

Lindley: What do you advise patients in terms of prevention with diet, exercise, and other approaches? And don’t we all have cancer?

Dr. Mukherjee: It depends on the type of cancer we’re talking about. Certainly, although cancer is absolutely linked to our genetics, various toxins unleash cancer, and smoking is one of them. There’s cancer in the genes, but there are many ways to prevent cancer. Avoiding smoking [and] exposure to blistering sunlight. There’s a link between diet and colon cancer, for example—so avoiding a low-fiber, red meat diet. Obesity has been linked to breast cancer. So there are a variety of things one can to do, and the National Cancer Institute has been very good about informing us on the various strategies that have been successful and linked to prevention.

Lindley: And isn’t screening important?

Dr. Mukherjee: Exactly. We now know that several screening strategies which are successful. Tomography is one and colonoscopy is another one that has been very successful.

Lindley: What do you hope readers come away with from your book, and what can they do to advance understanding of cancer?

Dr. Mukherjee: One thing readers can get from the book is how heterogeneous and complex this is disease is, and not to be nihilistic about our capacity to turn around cancer mortality and suffering over time. And what readers can do at every level from education to funding to public advocacy is to encourage scientific research. Reading and talking about science and medicine is important in our society—probably one of the most important things we face as a species. The book should remind us is to be connected to science and medicine, particularly in America where that connection is being lost every day.

Lindley: Many potential readers may see your book as a grim tome, yet you write of coming away from your work ebullient and joyful.

Dr. Mukherjee: It’s not grim. It’s a book of stories. I do think the history of cancer is something we need to come to terms with because it can show us what happens next and how we go on from here. It’s a disease that’s going to affect all our lives, so we really need to know about it. That’s why I think it’s important to read this history, and not just this book, but to read about the history of science in general.