Physician, researcher, and award-winning science writer, Siddhartha Mukherjee examines cancer with a cellular biologist’s precision, a historian’s perspective, and a biographer’s passion. The result is an astonishingly lucid and eloquent chronicle of a disease humans have lived with—and perished from—for more than five thousand years.
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 that, just three decades ago, was thought to be easily vanquished in an all-out “war against cancer.” The book reads like a literary thriller with cancer as the protagonist.
From the Persian Queen Atossa, whose Greek slave may have cut off her diseased breast, to the nineteenth-century recipients of primitive radiation and chemotherapy to Mukherjee’s own leukemia patient, Carla, The Emperor of All Maladies is about the people who have soldiered through fiercely demanding regimens in order to survive—and to increase our understanding of this iconic disease.
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 provides hope and clarity to those seeking to demystify cancer.
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The Emperor of all Maladies 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.
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.
Roiling underneath these medical, cultural, and metaphorical interceptions of cancer over the centuries was the biological understanding of the illness—an understanding that had morphed, often radically, from decade to decade. Cancer, we now know, is a disease caused by the uncontrolled growth of a single cell. This growth is unleashed by mutations—changes in DNA that specifically affect genes that incite unlimited cell growth. In a normal cell, powerful genetic circuits regulate cell division and cell death. In a cancer cell, these circuits have been broken, unleashing a cell that cannot stop growing.
That this seemingly simple mechanism—cell growth without barriers—can lie at the heart of this grotesque and multifaceted illness is a testament to the unfathomable power of cell growth. Cell division allows us as organisms to grow, to adapt, to recover, to repair—to live. And distorted and unleashed, it allows cancer cells to grow, to flourish, to adapt, to recover, and to repair—to live at the cost of our living. Cancer cells can grow faster, adapt better. They are more perfect versions of ourselves.
The secret to battling cancer, then, is to find means to prevent these mutations from occurring in susceptible cells, or to find means to eliminate the mutated cells without compromising normal growth. The conciseness of that statement belies the enormity of the task. Malignant growth and normal growth are so genetically intertwined that unbraiding the two might be one of the most significant scientific challenges faced by our species. Cancer is built into our genomes: the genes that unmoor normal cell division are not foreign to our bodies, but rather mutated, distorted versions of the very genes that perform vital cellular functions. And cancer is imprinted in our society: as we extend our life span as a species, we inevitably unleash malignant growth (mutations in cancer genes accumulate with aging; cancer is thus intrinsically related to age). If we seek immortality, then so, too, in a rather perverse sense, does the cancer cell.
How, precisely, a future generation might learn to separate the entwined strands of normal growth from malignant growth remains a mystery. (“The universe,” the twentieth-century biologist J. B. S. Haldane liked to say, “is not only queerer than we suppose, but queerer than we can suppose”—and so is the trajectory of science.) But this much is certain: the story, however it plays out, will contain indelible kernels of the past. It will be a story of inventiveness, resilience, and perseverance against what one writer called the most “relentless and insidious enemy” among human diseases. But it will also be a story of hubris, arrogance, paternalism, misperception, false hope, and hype, all leveraged against an illness that was just three decades ago widely touted as being “curable” within a few years.
In the bare hospital room ventilated by sterilized air, Carla was fighting her own war on cancer. When I arrived, she was sitting with peculiar calm on her bed, a schoolteacher jotting notes. (“But what notes?” she would later recall. “I just wrote and rewrote the same thoughts.”) Her mother, red-eyed and tearful, just off an overnight flight, burst into the room and then sat silently in a chair by the window, rocking forcefully. The din of activity around Carla had become almost a blur: nurses shuttling fluids in and out, interns donning masks and gowns, antibiotics being hung on IV poles to be dripped into her veins.
I explained the situation as best I could. Her day ahead would be full of tests, a hurtle from one lab to another. I would draw a bone marrow sample. More tests would be run by pathologists. But the preliminary tests suggested that Carla had acute lymphoblastic leukemia. It is one of the most common forms of cancer in children, but rare in adults. And it is—I paused here for emphasis, lifting my eyes up—often curable.
Curable. Carla nodded at that word, her eyes sharpening. Inevitable questions hung in the room: How curable? What were the chances that she would survive? How long would the treatment take? I laid out the odds. Once the diagnosis had been confirmed, chemotherapy would begin immediately and last more than one year. Her chances of being cured were about 30 percent, a little less than one in three.
We spoke for an hour, perhaps longer. It was now nine thirty in the morning. The city below us had stirred fully awake. The door shut behind me as I left, and a whoosh of air blew me outward and sealed Carla in.
Table of Contents
Author's Note xiii
Part 1 "Of blacke cholor, without boyling" 9
Part 2 An Impatient War 105
Part 3 "Will you turn me out if I can't get better?" 191
Part 4 Prevention is the Cure 235
Part 5 "A Distorted Version of Our Normal Selves" 335
Part 6 The Fruits of Long Endeavors 393
Atossa's War 461
Selected Bibliography 537
Photograph Credits 543
What People are Saying About This
"An inspiring account of a very personal battle against 'the plague of our generation.'" -Kirkus
Reading Group Guide
This reading group guide for The Emperor of All Maladies includes an introduction, discussion questions, and ideas for enhancing your book club. The suggested questions are intended to help your reading group find new and interesting angles and topics for your discussion. We hope that these ideas will enrich your conversation and increase your enjoyment of the book.
In The Emperor of All Maladies, Siddhartha Mukherjee offers a sweeping and erudite history of cancer—from its earliest incarnations in ancient texts up to recent and long-awaited breakthroughs in treatment. Populated by captivating characters, from the Persian Queen Atossa, who instructed her servant to cut out a malignant tumor in her breast, to Sidney Farber, whose tireless research into children’s leukemia ushered in the modern era of cancer research, and written in Mukherjee’s artful prose, The Emperor of All Maladies reads like a thrilling novel, with scientific triumphs and setbacks, personal rivalries and alliances. But set against the backdrop of changing politics and social values, it is also a history of human civilization seen through the prism of cancer, the world’s most pervasive, tenacious disease.
Questions and Topics for Discussion
1. Cancer is often described as a “modern” disease—yet its first description dates from 2500 B.C. In what sense, then, is cancer a disease of modern times? How does knowing its ancient history affect your notion of cancer?
2. Mukherjee frames the book around the story of his patient, Carla Reed, a teacher who is diagnosed with leukemia. What did you find interesting or important about Carla’s experience? How do you think she shaped the author’s life and thoughts?
3. Mukherjee writes how in the early 1950s The New York Times refused to print the word “cancer” (or “breast”). Compare this to how we view cancer today. Is there any difference in the way you discuss cancer as a political or news topic and how you discuss a cancer diagnosis among family and friends?
4. Looked at one way, Sidney Farber’s early clinical trials with antifolates in 1947 and 1948 were a failure, with all of his young leukemia patients eventually dying of the disease. But with the results of these trials, Mukherjee writes, Farber “saw a door open—briefly, seductively” (p. 36). How so? Why do Farber’s trials mark a turning point in the history of cancer research?
5. “The stories of my patients consumed me, and the decisions that I made haunted me,” Mukherjee says about working in a cancer clinic (p. 5). But in the 1970s, during the height of aggressive combination chemotherapy trials, Mukherjee paints a different picture of doctor-patient interaction: “The language of suffering had parted, with the ‘smiling oncologist’ on one side and his patients on the other.” How have the relationships between doctors and patients evolved along with cancer treatments? What could be done to restore some of the lapses in this relationship?
6. “‘Li was accused of experimenting on people,’ Freireich said. ‘But of course all of us were experimenting… To not experiment would mean to follow the old rules—to do absolutely nothing.’” Review the case of Min Chiu Li (pp. 135-138), and explain Emil Freireich’s quote. Do you think Li’s actions were ethical? How can doctors and scientists draw the line between reckless, unproven treatment and necessary experimentation for drug development?
7. How did Mary Lasker borrow from the worlds of business, advertising and even the military to build a nationwide effort to combat cancer? How might Lasker’s vision be invoked today to generate funding and national attention for breast or ovarian cancer?
8. So many of the scientific breakthroughs that impacted cancer research, such as Wilhelm Röntgen’s discovery of the X-Ray in 1895, occurred by accident. What other “chance” discoveries appear in the text?
9. Numerous advances in cancer research would have been impossible without patients willing to submit themselves to grueling experimental trials—experiences from which they did not benefit, but future cancer patients might. How would you counsel a friend or relative about submitting themselves to such experiments?
10. How is the early history of chemotherapy linked to the histories of colonialism, the Industrial Revolution, and World War Two?
11. Was the War on Cancer a failure? Why or why not?
12. How did the tobacco industry react to studies in the 1950s about the link between cigarettes and lung cancer? How did the industry’s reaction differ to that of the general public? Do you think cigarette companies should be legally liable for cancer and other health problems likely caused by smoking?
13. The 1980 Canadian mammography trial (see pp. 298-300) was possibly flawed because technicians disproportionately steered women with suspected breast cancer to get mammograms, likely out of compassion. Put yourself in the technicians’ shoes. Would you have allocated your friend to the mammogram group? If so, how can trials ever be randomized? Should a trial with a promising new drug be randomized—even if it means forcing some patients to be in the non-treatment group? What if a new treatment emerges for a deadly form of cancer? Should half the enrollees in the trial be forced to take sugar-pills to document the efficacy of the treatment?
14. On page 316, Mukherjee argues that “the trajectories of AIDS and cancer were destined to crisscross and intersect at many levels.” Do you agree with Mukherjee’s comparison? What did Susan Sontag mean when she said AIDS and cancer had both become “not just a biological disease but something much larger—a social and political category replete with its own punitive metaphors?”
15. Review the case of Nelene Fox (pp. 322-324), whose HMO, Health Net, refused in 1991 to pay for an expensive bone marrow transplant to treat her diagnosis of advances breast cancer, citing the procedure as “investigational.” In your view, was it appropriate for Health Net to refuse reimbursement? Should patients pay for expensive experimental treatments out of their own pocket? What if these experimental treatments turn out not to extend survival—as with Fox’s transplant?
16. The author says that he was motivated to write this book after a patient asked him, “What is cancer?” Mukherjee could not think of a book that would answer her question. So he wrote it. Does “knowing your enemy”—knowing cancer—bring some kind of comfort?
17. On page 459, Mukherjee writes, “As the fraction of those affected by cancer creeps inexorably in some nations from one in four to one in three to one in two, cancer, will indeed, be the normal—an inevitability.” Mukherjee makes this assessment despite the approval of oncogene-targeting drugs like Herceptin, which have given new hope to cancer patients, as well as promising efforts to sequence the cancer genome. At the end of The Emperor of All Maladies, do you come away with optimism about science’s efforts to combat cancer? Why or why not?
18. In the final chapter of the book, Mukherjee creates a fictional journey for Queen Atossa through time to demonstrate how cancer treatment has changed over the centuries. How might you have summarized this book? What image, or metaphor, emerges most powerfully at the end of this book?
19. Germaine Berne’s story, which ends the book, is not superficially a story of hope, since she ultimately dies from relapsed cancer. Yet Mukherjee portrays her as a symbol of our war on cancer. In what sense does Germaine epitomize the battle against cancer? How is her story a story of hope?
20. Mukherjee calls this book a “biography.” Can a “biography” be written of an illness? How might such a biography differ from the traditional biography of an individual? Are there other diseases that demand biographies, or is this project unique to cancer?
21. In what sense does history “repeat itself” in cancer research? In science, where new discoveries keep altering the landscape, what is the worth of reliving the past?
Enhance Your Book Club
1. Learn about cancer prevention. Before your book club meeting, have each member choose a type of cancer to research and prepare a brief presentation about warning signs and prevention. Learn more on the website for the American Cancer Society: http://www.cancer.org/Cancer/index.
2. Prepare for your next doctor appointment. In today’s health care system, patients often complain about doctors spending too little time with them or providing unsatisfactory explanations of medical conditions. Make a list of facts you learned from The Emperor of All Maladies with practical implications for your own healthcare, or questions that the book provoked. Discuss what you learned as a group, and then, during your next appointment, ask you doctor to clarify any topics you found unclear or confusing.
3. Get involved. The Emperor of All Maladies mentions several cancer charity organizations, such as The Jimmy Fund and St. Jude’s Children’s Research Hospital. Research local cancer charities in your area, and find out how you can donate time or money to their cause.
4. Read science news: The Emperor of All Maladies describes powerful stories that directly affect our lives: mammography, breast cancer treatment, cervical cancer prevention. Read updates on these in The New York Times, or other newspapers, and bring stories to the book club meeting to discuss.