The Emperor of All Maladies: A Biography of Cancer

Praise for

THE EMPEROR OF ALL MALADIES

Powerful and ambitious . . . One of the most extraordinary stories in medicine.

—THE NEW YORK TIMES BOOK REVIEW

One of the great books of this past year . . . A wonderful, smart book.

—Dr. Nancy Snyderman, chief medical editor, NBC’s TODAY Show

With this fat, enthralling, juicy, scholarly, wonderfully written history of cancer, Siddhartha Mukherjee vaults into that exalted company, inviting comparisons to the late physician and historian Lewis Thomas and the late paleontologist and historian of science Stephen Jay Gould. . . . What a story—full of quixotic characters, therapeutic triumphs and setbacks, and recent historical events—with all the hubris and pathos of Greek tragedy.

—THE WASHINGTON POST

"Magisterial . . . Reading The Emperor of All Maladies is a sharpening, clarifying, and moving experience. . . . One of the best reading experiences of my life."

—THE CLEVELAND PLAIN DEALER

Mukherjee’s book has the vividness of an insider’s account. It evokes what it feels like to be at the forefront of modern biomedicine and to bring new knowledge and technologies into the clinic. . . . 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 NEW YORKER

[Mukherjee] makes science not merely intelligible but thrilling. . . . A compulsively readable, surprisingly uplifting, and vivid tale.

—O, THE OPRAH MAGAZINE

A New York Times Bestseller

WINNER OF THE PULITZER PRIZE

WINNER OF THE INAUGURAL PEN/E. O. WILSON LITERARY SCIENCE WRITING AWARD

FINALIST FOR THE NATIONAL BOOK CRITICS CIRCLE AWARD

FINALIST FOR THE LOS ANGELES TIMES BOOK PRIZE

WINNER OF THE BOOKS FOR A BETTER LIFE AWARD

FINALIST FOR THE J. ANTHONY LUKAS BOOK PRIZE

An extraordinary achievement. —THE NEW YORKER

It’s time to welcome a new star in the constellation of great writer-doctors. —THE WASHINGTON POST

Magisterial . . . A small miracle of insight, scope, pace, structure, and lucidity.

—THE CLEVELAND PLAIN DEALER

This volume should earn Mukherjee a rightful place in the pantheon of our epoch’s great explicators. —THE BOSTON GLOBE

The Emperor of All Maladies is a magnificent, profoundly humane biography of cancer—from its first documented appearances thousands of years ago through the epic battles in the twentieth century to cure, control, and conquer it to a radical new understanding of its essence.

The story of cancer is a story of human ingenuity, resilience, and perseverance, but also of hubris, paternalism, and misperception. Mukherjee recounts centuries of discoveries, setbacks, victories, and deaths, told through the eyes of his predecessors and peers, training their wits against an infinitely resourceful adversary.

Riveting, urgent, and surprising, The Emperor of All Maladies provides a fascinating glimpse into the future of cancer treatments. It is an illuminating book that offers hope and clarity to those seeking to demystify cancer.

THIS EDITION INCLUDES A NEW INTERVIEW WITH THE AUTHOR

A New York Times Bestseller

NAMED A TOP TEN BOOK OF 2010 BY

The New York Times

O, The Oprah Magazine

Time

Entertainment Weekly

San Francisco Chronicle

ALSO NAMED A BEST BOOK OF 2010 BY

The New Yorker

NPR

The Economist

Bloomberg

The Vancouver Sun

The Washington Post

The Cleveland Plain Dealer

Pittsburgh Post-Gazette

The Raleigh News & Observer

Publishers Weekly

Kirkus Reviews

Further Acclaim for The Emperor of All Maladies

Mukherjee brings an impressive balance of empathy and dispassion to this instantly essential piece of medical journalism.

—Time

A meticulously researched, panoramic history… What makes Mukherjee’s narrative so remarkable is that he imbues decades of painstaking laboratory investigation with the suspense of a mystery novel and urgency of a thriller.… He possesses a striking gift for carving some of science’s most abstruse concepts into forms as easily understood and reconfigured as a child’s wooden blocks.

—The Boston Globe

Riveting and powerful… Mukherjee’s extraordinary book might stimulate a wider discussion of how to wisely allocate our precious health care resources.

—San Francisco Chronicle

Remarkable… The reader devours this fascinating book… Mukherjee is a clear and determined writer.… An unusually humble, insightful book.

—Los Angeles Times

Extraordinary… So often physician writers attempt the delicacy of using their patients as a mirror to their own humanity. Mukherjee does the opposite. His book is not built to show us the good doctor struggling with tough decisions, but ourselves.

—John Freeman, NPR

Now and then a writer comes along who helps us fathom both the intricacies of a scientific specialty and its human meaning. Lewis Thomas, Sherwin Nuland, and Oliver Sacks come to mind. Add to their company Siddhartha Mukherjee.

—Elle magazine

Rich and engrossing… With the perceptiveness and patience of a true scientist, [Mukherjee] begins to weave these individual threads into a coherent and engrossing narrative.

—The Economist

A brilliant, riveting history of the disease… Threaded throughout, and propelling the narrative forward, are the affecting tales of Mukherjee’s own patients.

—Entertainment Weekly

Ambitious… Mukherjee has a storyteller’s flair and a gift for translating complex medical concepts into simple language.

—The Wall Street Journal

Cancer has never been as fully explored as in Dr. Siddhartha Mukherjee’s fascinating and moving history.

—The Daily Beast

"With epic scope and passionate pen, The Emperor of All Maladies boldly addresses, then breaks down the monolith of disease."

—The Onion A.V. Club

Informative, elegant, comprehensive, and lucid.

—Pittsburgh Post-Gazette

Mukherjee’s elegant prose animates the science.

—Bloomberg News

Brilliant and riveting.

—Associated Press

[A] brilliant book.

—Larry King

A magnificent book.

—Sanjay Gupta, M.D., CNN

An ambitious scientific, political, and cultural history.

—Slate.com

Intensely readable.

—New York Post

Impressive.

—The Philadelphia Inquirer

Mukherjee… writes with supreme authority.

—The Seattle Times

Mukherjee makes us understand that along with our terrible losses, great gains have been made.

—Newsday

Eminently readable… A surprisingly accessible and encouraging narrative.

—Booklist (starred review)

A beautifully written account of the ingenuity, hubris, courage, and utter confusion humankind has brought to its attempts to grapple with cancer.

—Maclean’s

"Future biographers and historians of the disease will labor from deep with the long shadow cast by Siddhartha Mukherjee’s remarkable The Emperor of All Maladies.… A vivid and profoundly engaging read."

—BookPage

Sweeping… Mukherjee’s formidable intelligence and compassion produce a stunning account.

—Publishers Weekly (starred review)

"Siddhartha Mukherjee’s The Emperor of All Maladies left me shaken, fascinated, and not depressed, because he gives a face to our old enemy, cancer."

—Emma Donoghue, author of Room

"Sid Mukherjee’s book is a pleasure to read, if that is the right word.… His book is the clearest account I have read on this subject. With The Emperor of All Maladies, he joins that small fraternity of practicing doctors who can not just talk about their profession but write about it."

—Tony Judt, author of The Memory Chalet

Rarely have the science and poetry of illness been so elegantly braided together as they are in this erudite, engrossing, kind book.

—Andrew Solomon, National Book Award–winning author of The Noonday Demon

"At once learned and skeptical, unsentimental and humane, The Emperor of All Maladies is that rarest of things—a noble book."

—David Rieff, author of Swimming in a Sea of Death

A magisterial, wise, and deeply human piece of writing.

—Adam Hochschild, author of King Leopold’s Ghost and Bury the Chains

"The Emperor of All Maladies beautifully describes the nature of cancer from a patient’s perspective and how basic research has opened the door to understanding this disease."

—Bert Vogelstein, director, Ludwig Center at Johns Hopkins University

A labor of love… as comprehensive as possible.

—George Canellos, M.D., William Rosenberg Professor of Medicine, Harvard Medical School

"An elegant… tour de force. The Emperor of All Maladies reads like a novel… but it deals with real people and real successes, as well as with the many false notions and false leads. Not only will the book bring cancer research and cancer biology to the lay public, it will help attract young researchers to a field that is at once exciting and heart wrenching… and important."

—Donald Berry, Ph.D., MD Anderson Cancer Center, University of Texas

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To

ROBERT SANDLER (1945–1948),

and to those who came before

and after him.

Illness is the night-side of life, a more onerous citizenship. Everyone who is born holds dual citizenship, in the kingdom of the well and in the kingdom of the sick. Although we all prefer to use only the good passport, sooner or later each of us is obliged, at least for a spell, to identify ourselves as citizens of that other place.

—Susan Sontag

In 2010, about six hundred thousand Americans, and more than 7 million humans around the world, will die of cancer. In the United States, one in three women and one in two men will develop cancer during their lifetime. A quarter of all American deaths, and about 15 percent of all deaths worldwide, will be attributed to cancer. In some nations, cancer will surpass heart disease to become the most common cause of death.

Author’s Note

This book is a history of cancer. It is a chronicle of an ancient disease—once a clandestine, whispered-about illness—that has metamorphosed into a lethal shape-shifting entity imbued with such penetrating metaphorical, medical, scientific, and political potency that cancer is often described as the defining plague of our generation. This book is a biography in the truest sense of the word—an attempt to enter the mind of this immortal illness, to understand its personality, to demystify its behavior. But my ultimate aim is to raise a question beyond biography: Is cancer’s end conceivable in the future? Is it possible to eradicate this disease from our bodies and societies forever?

Cancer is not one disease but many diseases. We call them all cancer because they share a fundamental feature: the abnormal growth of cells. And beyond the biological commonality, there are deep cultural and political themes that run through the various incarnations of cancer to justify a unifying narrative. It is not possible to consider the stories of every variant of cancer, but I have attempted to highlight the large themes that run through this 4,000-year history.

The project, evidently vast, began as a more modest enterprise. In the summer of 2003, having completed a residency in medicine and graduate work in cancer immunology, I began advanced training in cancer medicine (medical oncology) at the Dana-Farber Cancer Institute and Massachusetts General Hospital in Boston. I had initially envisioned writing a journal of that year—a view-from-the-trenches of cancer treatment. But that quest soon grew into a larger exploratory journey that carried me into the depths not only of science and medicine, but of culture, history, literature, and politics, into cancer’s past and into its future.

Two characters stand at the epicenter of this story—both contemporaries, both idealists, both children of the boom in postwar science and technology in America, and both caught in the swirl of a hypnotic, obsessive quest to launch a national War on Cancer. The first is Sidney Farber, the father of modern chemotherapy, who accidentally discovers a powerful anti-cancer chemical in a vitamin analogue and begins to dream of a universal cure for cancer. The second is Mary Lasker, the Manhattan socialite of legendary social and political energy, who joins Farber in his decades-long journey. But Lasker and Farber only exemplify the grit, imagination, inventiveness, and optimism of generations of men and women who have waged a battle against cancer for four thousand years. In a sense, this is a military history—one in which the adversary is formless, timeless, and pervasive. Here, too, there are victories and losses, campaigns upon campaigns, heroes and hubris, survival and resilience—and inevitably, the wounded, the condemned, the forgotten, the dead. In the end, cancer truly emerges, as a nineteenth-century surgeon once wrote in a book’s frontispiece, as the emperor of all maladies, the king of terrors.

A disclaimer: in science and medicine, where the primacy of a discovery carries supreme weight, the mantle of inventor or discoverer is assigned by a community of scientists and researchers. Although there are many stories of discovery and invention in this book, none of these establishes any legal claims of primacy.

This work rests heavily on the shoulders of other books, studies, journal articles, memoirs, and interviews. It rests also on the vast contributions of individuals, libraries, collections, archives, and papers acknowledged at the end of the book.

One acknowledgment, though, cannot be left to the end. This book is not just a journey into the past of cancer, but also a personal journey of my coming-of-age as an oncologist. That second journey would be impossible without patients, who, above and beyond all contributors, continued to teach and inspire me as I wrote. It is in their debt that I stand forever.

This debt comes with dues. The stories in this book present an important challenge in maintaining the privacy and dignity of these patients. In cases where the knowledge of the illness was already public (as with prior interviews or articles) I have used real names. In cases where there was no prior public knowledge, or when interviewees requested privacy, I have used a false name, and deliberately confounded dates and identities to make it difficult to track them. However, these are real patients and real encounters. I urge all my readers to respect their identities and boundaries.

Prologue

Diseases desperate grown

By desperate appliance are relieved,

Or not at all.

—William Shakespeare, Hamlet

Cancer begins and ends with people. In the midst of scientific abstraction, it is sometimes possible to forget this one basic fact.… Doctors treat diseases, but they also treat people, and this precondition of their professional existence sometimes pulls them in two directions at once.

—June Goodfield

On the morning of May 19, 2004, Carla Reed, a thirty-year-old kindergarten teacher from Ipswich, Massachusetts, a mother of three young children, woke up in bed with a headache. Not just any headache, she would recall later, but a sort of numbness in my head. The kind of numbness that instantly tells you that something is terribly wrong.

Something had been terribly wrong for nearly a month. Late in April, Carla had discovered a few bruises on her back. They had suddenly appeared one morning, like strange stigmata, then grown and vanished over the next month, leaving large map-shaped marks on her back. Almost indiscernibly, her gums had begun to turn white. By early May, Carla, a vivacious, energetic woman accustomed to spending hours in the classroom chasing down five- and six-year-olds, could barely walk up a flight of stairs. Some mornings, exhausted and unable to stand up, she crawled down the hallways of her house on all fours to get from one room to another. She slept fitfully for twelve or fourteen hours a day, then woke up feeling so overwhelmingly tired that she needed to haul herself back to the couch again to sleep.

Carla and her husband saw a general physician and a nurse twice during those four weeks, but she returned each time with no tests and without a diagnosis. Ghostly pains appeared and disappeared in her bones. The doctor fumbled about for some explanation. Perhaps it was a migraine, she suggested, and asked Carla to try some aspirin. The aspirin simply worsened the bleeding in Carla’s white gums.

Outgoing, gregarious, and ebullient, Carla was more puzzled than worried about her waxing and waning illness. She had never been seriously ill in her life. The hospital was an abstract place for her; she had never met or consulted a medical specialist, let alone an oncologist. She imagined and concocted various causes to explain her symptoms—overwork, depression, dyspepsia, neuroses, insomnia. But in the end, something visceral arose inside her—a seventh sense—that told Carla something acute and catastrophic was brewing within her body.

On the afternoon of May 19, Carla dropped her three children with a neighbor and drove herself back to the clinic, demanding to have some blood tests. Her doctor ordered a routine test to check her blood counts. As the technician drew a tube of blood from her vein, he looked closely at the blood’s color, obviously intrigued. Watery, pale, and dilute, the liquid that welled out of Carla’s veins hardly resembled blood.

Carla waited the rest of the day without any news. At a fish market the next morning, she received a call.

We need to draw some blood again, the nurse from the clinic said.

When should I come? Carla asked, planning her hectic day. She remembers looking up at the clock on the wall. A half-pound steak of salmon was warming in her shopping basket, threatening to spoil if she left it out too long.

In the end, commonplace particulars make up Carla’s memories of illness: the clock, the car pool, the children, a tube of pale blood, a missed shower, the fish in the sun, the tightening tone of a voice on the phone. Carla cannot recall much of what the nurse said, only a general sense of urgency. Come now, she thinks the nurse said. Come now.

I heard about Carla’s case at seven o’clock on the morning of May 21, on a train speeding between Kendall Square and Charles Street in Boston. The sentence that flickered on my beeper had the staccato and deadpan force of a true medical emergency: Carla Reed/New patient with leukemia/14th Floor/Please see as soon as you arrive. As the train shot out of a long, dark tunnel, the glass towers of the Massachusetts General Hospital suddenly loomed into view, and I could see the windows of the fourteenth floor rooms.

Carla, I guessed, was sitting in one of those rooms by herself, terrifyingly alone. Outside the room, a buzz of frantic activity had probably begun. Tubes of blood were shuttling between the ward and the laboratories on the second floor. Nurses were moving about with specimens, interns collecting data for morning reports, alarms beeping, pages being sent out. Somewhere in the depths of the hospital, a microscope was flickering on, with the cells in Carla’s blood coming into focus under its lens.

I can feel relatively certain about all of this because the arrival of a patient with acute leukemia still sends a shiver down the hospital’s spine—all the way from the cancer wards on its upper floors to the clinical laboratories buried deep in the basement. Leukemia is cancer of the white blood cells—cancer in one of its most explosive, violent incarnations. As one nurse on the wards often liked to remind her patients, with this disease even a paper cut is an emergency.

For an oncologist in training, too, leukemia represents a special incarnation of cancer. Its pace, its acuity, its breathtaking, inexorable arc of growth forces rapid, often drastic decisions; it is terrifying to experience, terrifying to observe, and terrifying to treat. The body invaded by leukemia is pushed to its brittle physiological limit—every system, heart, lung, blood, working at the knife-edge of its performance. The nurses filled me in on the gaps in the story. Blood tests performed by Carla’s doctor had revealed that her red cell count was critically low, less than a third of normal. Instead of normal white cells, her blood was packed with millions of large, malignant white cells—blasts, in the vocabulary of cancer. Her doctor, having finally stumbled upon the real diagnosis, had sent her to the Massachusetts General Hospital.

In the long, bare hall outside Carla’s room, in the antiseptic gleam of the floor just mopped with diluted bleach, I ran through the list of tests that would be needed on her blood and mentally rehearsed the conversation I would have with her. There was, I noted ruefully, something rehearsed and robotic even about my sympathy. This was the tenth month of my fellowship in oncology—a two-year immersive medical program to train cancer specialists—and I felt as if I had gravitated to my lowest point. In those ten indescribably poignant and difficult months, dozens of patients in my care had died. I felt I was slowly becoming inured to the deaths and the desolation—vaccinated against the constant emotional brunt.

There were seven such cancer fellows at this hospital. On paper, we seemed like a formidable force: graduates of five medical schools and four teaching hospitals, sixty-six years of medical and scientific training, and twelve postgraduate degrees among us. But none of those years or degrees could possibly have prepared us for this training program. Medical school, internship, and residency had been physically and emotionally grueling, but the first months of the fellowship flicked away those memories as if all of that had been child’s play, the kindergarten of medical training.

Cancer was an all-consuming presence in our lives. It invaded our imaginations; it occupied our memories; it infiltrated every conversation, every thought. And if we, as physicians, found ourselves immersed in cancer, then our patients found their lives virtually obliterated by the disease. In Aleksandr Solzhenitsyn’s novel Cancer Ward, Pavel Nikolayevich Rusanov, a youthful Russian in his midforties, discovers that he has a tumor in his neck and is immediately whisked away into a cancer ward in some nameless hospital in the frigid north. The diagnosis of cancer—not the disease, but the mere stigma of its presence—becomes a death sentence for Rusanov. The illness strips him of his identity. It dresses him in a patient’s smock (a tragicomically cruel costume, no less blighting than a prisoner’s jumpsuit) and assumes absolute control of his actions. To be diagnosed with cancer, Rusanov discovers, is to enter a borderless medical gulag, a state even more invasive and paralyzing than the one that he has left behind. (Solzhenitsyn may have intended his absurdly totalitarian cancer hospital to parallel the absurdly totalitarian state outside it, yet when I once asked a woman with invasive cervical cancer about the parallel, she said sardonically, "Unfortunately, I did not need any metaphors to read the book. The cancer ward was my confining state, my prison.")

As a doctor learning to tend cancer patients, I had only a partial glimpse of this confinement. But even skirting its periphery, I could still feel its power—the dense, insistent gravitational tug that pulls everything and everyone into the orbit of cancer. A colleague, freshly out of his fellowship, pulled me aside on my first week to offer some advice. It’s called an immersive training program, he said, lowering his voice. But by immersive, they really mean drowning. Don’t let it work its way into everything you do. Have a life outside the hospital. You’ll need it, or you’ll get swallowed.

But it was impossible not to be swallowed. In the parking lot of the hospital, a chilly, concrete box lit by neon floodlights, I spent the end of every evening after rounds in stunned incoherence, the car radio crackling vacantly in the background, as I compulsively tried to reconstruct the events of the day. The stories of my patients consumed me, and the decisions that I made haunted me. Was it worthwhile continuing yet another round of chemotherapy on a sixty-six-year-old pharmacist with lung cancer who had failed all other drugs? Was is better to try a tested and potent combination of drugs on a twenty-six-year-old woman with Hodgkin’s disease and risk losing her fertility, or to choose a more experimental combination that might spare it? Should a Spanish-speaking mother of three with colon cancer be enrolled in a new clinical trial when she can barely read the formal and inscrutable language of the consent forms?

Immersed in the day-to-day management of cancer, I could only see the lives and fates of my patients played out in color-saturated detail, like a television with the contrast turned too high. I could not pan back from the screen. I knew instinctively that these experiences were part of a much larger battle against cancer, but its contours lay far outside my reach. I had a novice’s hunger for history, but also a novice’s inability to envision it.

But as I emerged from the strange desolation of those two fellowship years, the questions about the larger story of cancer emerged with urgency: How old is cancer? What are the roots of our battle against this disease? Or, as patients often asked me: Where are we in the war on cancer? How did we get here? Is there an end? Can this war even be won?

This book grew out of the attempt to answer these questions. I delved into the history of cancer to give shape to the shape-shifting illness that I was confronting. I used the past to explain the present. The isolation and rage of a thirty-six-year-old woman with stage III breast cancer had ancient echoes in Atossa, the Persian queen who swaddled her diseased breast in cloth to hide it and then, in a fit of nihilistic and prescient fury, possibly had a slave cut it off with a knife. A patient’s desire to amputate her stomach, ridden with cancer—sparing nothing, as she put it to me—carried the memory of the perfection-obsessed nineteenth-century surgeon William Halsted, who had chiseled away at cancer with larger and more disfiguring surgeries, all in the hopes that cutting more would mean curing more.