‘Cancer: The Emperor of All Maladies,’ with Prof. Siddhartha Mukherjee, Begins March 30 on PBS

For much of the 20th century, cancer was a word to be whispered, a topic avoided in polite conversation, its diagnosis a virtual death sentence. The stigma was such that in the 1950s, when a woman called The New York Times to place an advertisement for a breast cancer survivors group, she was greeted with a long pause. “We can’t place such an ad because it uses the words ‘breast’ and ‘cancer,’” she was told. “What if we call it ‘diseases of the chest wall’?”

“In the 1950s you would be confused about cancer because there wasn’t enough information,” says Siddhartha Mukherjee, an assistant professor of medicine at Columbia University Medical Center and author of the Pulitzer Prize-winning The Emperor of All Maladies: A Biography of Cancer. “That has changed dramatically. Today you could be confused about it because there’s too much information, and it’s coming from every direction.”

Mukherjee, who recounted the anecdote in his 2010 book, marvels at how far cancer research and care has come in the five years since then. The book has now been adapted into a three-part PBS documentary that will air nightly at 9 p.m. from March 30 to April 1. Ken Burns is the executive producer and Barak Goodman (JRN’86) is the director.

Mukherjee, Burns and Goodman were at Columbia on March 24 when the University hosted a media briefing on the future of cancer research. Speakers and panelists included Katie Couric, a co-founder of Stand Up to Cancer, and Columbia researchers Kenneth Forde, Stephen Emerson and Thomas Maniatis.

"Many people outside Columbia know Sid for his remarkable book, and now many more will learn the history he's told through the PBS series," said Columbia President Lee C. Bollinger. "We know him as a respected biomedical researcher and clinician whose work whose collaboration with colleagues across the University plays a role in our precision medicine initiative, which holds such promise for cancer and so many other medical challenges."

The main impetus for his book, and the documentary, was to illustrate where cancer research is and where it is headed. ”There’s no better road map than looking at history,” Mukherjee said. “History tells us where we’ve been, what mistakes we’ve made, what we’ve learned and how that knowledge is slowly being transformed into prevention, treatments and a cure.”

Q. What compelled you to write The Emperor of All Maladies in the first place?

A patient asked me, “What is it that I’m fighting?” And I found it embarrassing that in 2006, we could not provide patients with a very simple answer to where we were in the war on cancer. So I wrote the book for patients, but I really wrote it for myself, and for the field, to try to update myself, and others, as to where we were.

Q. Did you have any idea about the reception it would get?

When you write books, you don’t have any expectations that you will win prizes or they will get made into documentaries by someone like Ken Burns. You put your effort into the content, and if the content rings true to readers, then it’s a reflection of the fact that the subject is important. When I first approached publishers, I thought people would say, “Who wants to read a 600-page book on cancer?” But the response was staggering. The same thing happened when Ken began to look for people to fund the documentary. We were able to fund the film within the first few months, which almost never happens in documentary filmmaking.

Q. And how did the documentary come about?

It was through a number of fortuitous collaborations. Before the book was in the public space, we were sending out pre-publication copies. Laura Ziskin, a founder of Stand Up to Cancer, who has since passed away from breast cancer, read a copy, made a cold call and said, “Look, I think that this would make an incredibly important documentary film, and I want to do it.” [Ziskin was a movie producer whose credits include the Spider-Man films and Pretty Woman.] Two weeks later, I received a second phone call, from Ken Burns, saying that he wanted to convert it into a film. This made things complicated, but we wanted the reach of public television, and we wanted to work with Stand Up to Cancer because of its enormous advocacy around the disease. So we brought together public television, Stand Up to Cancer and the book in a tripartite collaboration.

Siddhartha Mukherjee with executive producer Ken Burns. Photo by ©Stephanie Berger

Q. The documentary is coming out five years after the book. What has happened since then in the treatment and research of the disease?

An enormous amount. We’ve seen the birth of revolutionary new ways of thinking about and treating cancer. There’s immunotherapy, where the immune system can be activated to fight cancer cells and eliminate cancers. Patients’ own T cells are being modified and re-infused back into them so they can become cancer killers. And our understanding of what cancer is, at a cellular level, has changed. We used to think about cancer as a disease of growth, obviously, but we now know there are many things that are linked to growth. For instance, what we know about the link between metabolism and growth, how cancer cells consume sugar, oxygen and various other nutrients from the environment, has really changed. We’ve begun to understand the cancer cell at that level. Also, the relationship between viruses and cancer has been illuminated by multiple studies, and the fact that you can vaccinate and prevent cancers such as those caused by the human papillomavirus.

Q. Tom Maniatis, chair of the department of biochemistry and molecular biophysics at the Medical Center, was named director of Columbia’s precision medicine initiative last fall. He says that precision medicine will have an impact on health care in ways we’ve never seen before. How will that relate to cancer?

Today we know there are many kinds of cancers, even within a particular type. Every cancer patient has a unique set of mutations, a unique cancer. One woman’s breast cancer, in a genetic sense, is different from another woman’s breast cancer, even though they might share some common features. Do you have to invent a new cancer cocktail for every patient? One of the real challenges is to figure out what are the common rules in cancer, and are they common enough that we can imagine treatments? Or are they so different among patients that we have to imagine a precision approach to every single patient? And how can you do this in a cost-effective manner? In other words, we’re trying to reinvent the very rules that govern what we know of cancer.

Q. What is your lab working on?

Our laboratory works on two kinds of problems. One, broadly speaking, is the development of blood and how it is abnormal in patients with leukemia and myelodysplastic syndrome (MDS). We are trying to figure out how stem cells generate blood and how some components of that may go wrong in patients with MDS and what to do about it. The second problem is the biology of bone and bone marrow. How do the support structures of the body—bone, skeletal tissue, cartilage, etc.—get generated and collaborate with the genesis of blood? These two interact, and our job is to figure out how they regulate each other. We have a very active ongoing study in collaboration with other Columbia investigators that addresses this very interesting question in biology. Patients treated at Columbia have their bone marrow and all their cancer tissue put into a bank, which runs through the entire lifetime of the patient. Over 10 years, over 20 years, every biopsy that’s performed is stored in this common tissue bank. This gives you a snapshot of the evolution of cancer in a single patient. You can see what the disease was like 15 years ago and what it is going to be like as it moves forward. It’s like putting evolution into a tissue bank, and cancer is an evolutionary disease. We have tried to think about how to use these resources to deliver integrated, personalized care to cancer patients, particularly those with leukemias.

Q. What makes the fact that you’re doing this work at Columbia right now distinctive?

We have an incredible set of resources at Columbia that are unmatched around the world: a hospital where patients come from the large community around campus and a state-of-the-art academic medical center, giving us the capacity to collaborate with leaders in the field. I can walk down one floor and have a conversation with [Professor and Director of Institute for Cancer Genetics] Riccardo Dalla-Favera, one of the world’s great leaders of lymphoma, or go two floors down and talk to an expert in leukemia. You can have meaningful interaction within the cancer center, but cancer is not just a cell in isolation. To understand cancer you need to understand its physiological context, which means to collaborate with people who don’t necessarily work on cancer. And to treat cancer you need a similarly collaborative context in which you are asking for help from people in kidney diseases, bone diseases, from doctors in the neurological center. This kind of collaboration plays to the strengths of Columbia’s departments.

Q. You are married to another Columbia professor, Sarah Sze, who is on the visual arts faculty in the School of the Arts. Does your work in the arts and sciences overlap in any way?

On the day-to-day level, of course, my work has very little to do with the arts. But the intriguing issues about how to be creative—what does it mean to ask the right question—those are the same. We’ve done a few public talks—one at the Museum of Modern Art, one at the Asia Society—and I think they provide an insight into how our work intersects and how it’s different. In general, though, we try to avoid making broad generalizations about two very different spheres of work, science and the arts.

Q. In the introduction of your book you ask if it is possible to eradicate cancer from our bodies and societies forever. Are you closer to an answer now?

The question is whether you can imagine an end to cancer, and the answer is probably no, but a thoughtful no. Cancer is a genetic disease. It’s caused by a combination of environmental influences that ultimately activate or inactivate genes that eventually unleash the abnormal growth pattern in a cell. Some of these genes are mutated because of alterations in the environment – carcinogens, viruses—but some of the genetic mutations are nature’s accidents, which have to do, ultimately, with the fact that our cells have exquisitely controlled genes and genetic networks that control growth. We can certainly eliminate important carcinogens in the world, we can vaccinate against viruses that cause cancer, and we can look for defects in gene cell copying that result in mutations. In the end we will prevent some cancers, treat some cancers and cure some other cancers. And some will remain challenges, reflecting the complex biology of this disease.