The Emperor of All Maladies A Biography of Cancer

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 SCRIBNER
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Copyright © 2010 by Siddhartha Mukherjee, M.D.

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First Scribner hardcover edition November 2010

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Photograph credits appear on page 543.

 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
 Contents

Author’s Note

Prologue
Part One: “Of blacke cholor, without boyling”
Part Two: An Impatient War
Part Three: “Will you turn me out if I can’t get better?”
Part Four: Prevention Is the Cure
Part Five: “A Distorted Version of Our Normal Selves”
Part Six: The Fruits of Long Endeavors
Atossa’s War

Acknowledgments
Notes
Glossary
Selected Bibliography
Photograph Credits
Index
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?
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 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 cancer-affected breast in
cloth to hide it and then, in a fit of nihilistic and prescient fury, had a slave