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The Mind of a Disease

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THE EMPEROR OF ALL MALADIES

A Biography of Cancer

By

Siddhartha Mukherjee

Illustrated. 571 pp. Scribner. $30

 

All patients begin as storytellers, the oncologist Siddhartha Mukherjee observes near the start of this powerful and ambitious first book. Long before they see a doctor, they become narrators of suffering, as Mukherjee puts it — travelers who have visited the “kingdom of the ill.”

Many doctors become storytellers too, and Mukherjee has undertaken one of the most extraordinary stories in medicine: a history of cancer, which will kill about 600,000 Americans by the end of this year, and more than seven million people around the planet. He frames it as a biography, “an attempt to enter the mind of this immortal illness, to understand its personality, to demystify its behavior.” It is an epic story that he seems compelled to tell, the way a passionate young priest might attempt a biography of Satan.

Mukherjee started on the road to this book when he began advanced training in cancer medicine at the Dana-Farber Cancer Institute in Boston in the summer of 2003. During his first week, a colleague who’d just completed the program took him aside. “It’s called an immersive training program. But by immersive, they really mean drowning,” he said, lowering his voice the way many of us do when we speak of cancer itself. “Have a life outside the hospital,” the doctor warned him. “You’ll need it, or you’ll get swallowed.”

“But it was impossible not to be swallowed,” Mukherjee writes. At the end of every evening he found himself stunned and speechless in the neon floodlights of the hospital parking lot, compulsively trying to reconstruct the day’s decisions and prescriptions, almost as consumed as his patients by the dreadful rounds of chemotherapy and the tongue-twisting names of the drugs, “Cyclophosphamide, cytarabine, prednisone, asparaginase. . . .”

Eventually he started this book so as not to drown.

The oldest surviving description of cancer is written on a papyrus from about 1600 B.C. The hieroglyphics record a probable case of breast cancer: “a bulging tumor . . . like touching a ball of wrappings.” Under “treatment,” the scribe concludes: “none.”

For more than 2,000 years afterward, there is virtually nothing about cancer in the medical literature (“or in any other literature,” Mukherjee adds.) The modern understanding of the disease originated with the recognition, in the first half of the 19th century, that all plants and animals are made of cells, and that all cells arise from other cells. The German researcher Rudolph Virchow put that in Latin: omnis cellula e cellula.

Cancer is a disease that begins when a single cell, among all the trillions in a human body, begins to grow out of control. Lymphomas, leukemias, malignant melanomas, sarcomas all begin with that microscopic accident, a mutation in one cell: omnis cellula e cellula e cellula. Cell growth is the secret of living, the source of our ability to build, adapt, repair ourselves; and cancer cells are rebels among our own cells that outrace the rest. “If we seek immortality,” Mukherjee writes, “then so, too, in a rather perverse sense, does the cancer cell.”

Mukherjee opens his book with the story of one of the founders of the hospital where he trained — Sidney Farber, a specialist in children’s diseases who began as a pathologist. In 1947, Farber worked in a tiny, dank laboratory in Boston, dissecting specimens and performing autopsies. He was fascinated by a sharklike species of cancer called acute lymphoblastic leukemia, which can move so fast that it kills an apparently healthy child within only a few days. A patient would be “brought to the hospital in a flurry of excitement, discussed on medical rounds with professorial grandiosity” and then sent home to die.

In the summer of 1947, a 2-year-old boy, the child of a Boston shipyard worker, fell sick. Examining a drop of the baby’s blood through the microscope, Farber saw the telltale signs of acute lymphoblastic leukemia, billions of malignant white cells “dividing in frenzy, their chromosomes condensing and uncondensing, like tiny clenched and unclenched fists.” By December, the boy was near death. In the last days of the year, Farber injected his patient with an experimental drug, aminopterin, and within two weeks he was walking, talking and eating again. It wasn’t a cure, only a remission; but for Farber it was the beginning of a dream of cures, of what one researcher called “a penicillin for cancer.”

The next year, Farber helped start a research fund drive around a boy who suffered from a lymphoma in his intestines, a disease that killed 90 percent of its victims. The boy was cherubic and blond, an enormous fan of the Boston Braves, and his name was Einar Gustafson. For the sake of publicity, Farber rechristened him Jimmy. That May, the host of the radio show “Truth or Consequences” interrupted his usual broadcast to bring his listeners into Jimmy’s hospital room to listen in as players on the Braves marched into Jimmy’s room and sang “Take Me Out to the Ball Game.”

By the summer of 1952, Farber had built an imposing new hospital, Jimmy’s Clinic. Soon, he was working on an even grander scale, with the help of an extraordinary socialite and medical philanthropist, Mary Lasker. (“I am opposed to heart attacks and cancer,” she once told a reporter, “the way one is opposed to sin.”) Mary and her husband, Albert, an advertising executive, joined forces with Farber. They wanted, as Mukherjee writes, “a Manhattan Project for cancer.” Together, through masterly advertising, fund-raising and passion for their common cause (“The iron is hot and this is the time to pound without cessation,” Farber wrote to Mary Lasker), they maneuvered the United States into what would become known as the war on cancer. Richard Nixon signed it into law with the National Cancer Act in 1971, authorizing the spending of $1.5 billion of research funds over the next three years.

In political terms, the war was well timed, coming at a time when America’s collective nightmares were no longer “It Came From Outer Space” or “The Man From Planet X,” but “The Exorcist” and “They Came from Within.” Mary Lasker called the war on cancer the country’s next moon shot, the conquest of inner space.

In scientific terms, however, the war was disastrously premature. The moon race had been based on rocket science. But in the early 1970s, there really wasn’t a science of cancer. Researchers still did not understand what makes cells turn malignant. Now that they were so much in the spotlight, and in the money, they fell into bickering, demoralized, warring factions. The “iconic battleground” of the time was the chemotherapy ward, Mukherjee writes, “a sanitized vision of hell.” Typically it was a kind of limbo, almost a jail, in which absolutely no one spoke the word “cancer,” the inmates’ faces had an orange tinge from the drugs they were given, and windows were covered with heavy wire mesh to keep them from committing suicide. “The artifice of manufactured cheer (a requirement for soldiers in battle) made the wards even more poignantly desolate,” Mukherjee writes.

“The Emperor of All Maladies” is a history of eureka moments and decades of despair. Mukherjee describes vividly the horrors of the radical mastectomy, which got more and more radical, until it arrived at “an extraordinarily morbid, disfiguring procedure in which surgeons removed the breast, the pectoral muscles, the axillary nodes, the chest wall and occasionally the ribs, parts of the sternum, the clavicle and the lymph nodes inside the chest.” Cancer surgeons thought, mistakenly, that each radicalization of the procedure was progress. “Pumped up with self-confidence, bristling with conceit and hypnotized by the potency of medicine, oncologists pushed their patients — and their discipline — to the brink of disaster,” Mukherjee writes. In this army, “lumpectomy” was originally a term of abuse.

Meanwhile, more Americans were dying of cancer than ever, mainly because of smoking. Back in 1953, the average adult American smoked 3,500 cigarettes a year, or about 10 a day. Almost half of all Americans smoked. By the early 1940s, as one epidemiologist wrote, “asking about a connection between tobacco and cancer was like asking about an association between sitting and cancer.” In the decade and a half after Nixon declared his war on cancer, lung cancer deaths among older women increased by 400 percent. That epidemic is still playing itself out.

Mukherjee is good on the propaganda campaign waged by the tobacco companies, “the proverbial combination of smoke and mirrors.” As one internal industry report noted in 1969, “Doubt is our product, since it is the best means of competing with the ‘body of fact.’ ” This episode makes particularly interesting reading to anyone following the current propaganda campaigns against the science of climate change.

Meanwhile, those who studied the causes of cancer in the laboratories and those who treated it in the clinics were not always talking to each other. As Mukherjee puts it, “The two conversations seemed to be occurring in sealed and separate universes.” The disease was hard to understand either intellectually, in the lab, or emotionally, in the clinic. In the lab, because it is so heterogeneous in its genetics and its migrations in the body. In the hospital, because its course is horrible and so often slow, drawn out. When it comes to cancer, Mukherjee writes, “dying, even more than death, defines the illness.”

Mukherjee stitches stories of his own patients into this history, not always smoothly. But they are very strong, well-written and unsparing of himself: “Walking across the hospital in the morning to draw yet another bone-marrow biopsy, with the wintry light crosshatching the rooms, I felt a certain dread descend on me, a heaviness that bordered on sympathy but never quite achieved it.”

The heroes of the last few decades of this epic history are Robert Weinberg, Harold Varmus, Bert Vogelstein and the other extraordinary laboratory scientists who have finally worked out the genetics of cancer, and traced the molecular sequence of jammed accelerators and missing brakes that release those first rebel cells. As James Watson wrote not long ago, “Beating cancer now is a realistic ambition because, at long last, we largely know its true genetic and chemical characteristics.” We may finally be ready for war.

As a clinician, Mukherjee is only guardedly optimistic. One of the constants in oncology, as he says, is “the queasy pivoting between defeatism and hope.” Cancer is and may always be part of the burden we carry with us — the Greek word onkos means “mass” or “burden.” As Mukherjee writes, “Cancer is indeed the load built into our genome, the leaden counterweight to our aspirations for immortality.” But onkos comes from the ancient Indo-European nek, meaning to carry the burden: the spirit “so inextricably human, to outwit, to outlive and survive.” Mukherjee has now seen many patients voyage into the night. “But surely,” he writes, “it was the most sublime moment of my clinical life to have watched that voyage in reverse, to encounter men and women returning from that strange country— to see them so very close, ­clambering back.”

Reviewed by

Jonathan Weiner is the Maxwell M. Geffen professor of medical and scientific journalism at Columbia University. His latest book is “Long for This World: The Strange Science of Immortality.”

Courtesy: http://www.nytimes.com

Filed under: Book of the week, ,

Siddhartha Mukherjee

Chang W. Lee/The New York Times

Dr. Siddhartha Mukherjee in his lab at the Herbert Irving Comprehensive Cancer Center.

Siddhartha Mukherjee is a cancer physician and researcher. He is an assistant professor of medicine at Columbia University and a staff cancer physician at Columbia University Medical Center. A Rhodes scholar, he graduated from Stanford University, University of Oxford, Harvard Medical School. He has published articles in Nature, The New England Journal of Medicine, The New York Times, and The New Republic. He lives in New York with his wife and daughters.

His book, “The Emperor of All Maladies: A Biography of Cancer,” won the 2011 Pulitzer prize for general nonfiction.

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In Dr. Siddhartha Mukherjee’s lab, a Stanley Kubrick-like space at the Herbert Irving Comprehensive Cancer Center at Columbia University, enormous white freezers with digital temperature readouts keep tissue at 80 below zero. Sterile work stations with transparent hoods and bacteria-scattering blowers emit an unearthly blue light. And there is a bountiful supply of mice that, thanks to the addition of a jellyfish gene, literally glow either red or green in the dark.

Under the microscope, their blood-forming stem cells, a particular interest of Dr. Mukherjee’s right now, shine like tiny Christmas lights. Just recently, he said, he and his team had discovered what may be a new mutation associated with the precancerous condition myelodysplasia.

“Cell culture is a little like gardening,” he added. “You sit and you look at cells, and then you see something and say, ‘You know, that doesn’t look right.’ “

Dr. Mukherjee, an oncologist and assistant professor of medicine at Columbia, known as Sid by his friends, is married to the MacArthur award-winning artist Sarah Sze and looks less like a scientist than like the leading man in a Bollywood musical. He belongs to that breed of physicians, rapidly multiplying these days, who also have literary DNA in their genome, and his first book, “The Emperor of All Maladies: A Biography of Cancer,” comes out from Scribner on Nov. 16.

The book tells the stories of several cancer patients, and also of heroic researchers like Sidney Farber, who pioneered the treatment of childhood leukemia. But its main character, as the subtitle suggests, is the disease itself as it has been diagnosed, treated and thought about over the last 4,000 years.

In the early 1950s, Dr. Mukherjee points out in the book, cancer was still considered so unmentionable that a woman seeking to place an advertisement in The New York Times for a support group was told that the paper could not print either the word “breast” or the word “cancer.” How about “diseases of the chest wall,” an editor helpfully suggested. Then, a few decades later, cancer was in the public limelight, thought to be virtually curable if we just waged sufficient “war” against it.

What we understand now, thanks to advances in cell biology, Dr. Mukherjee writes, is that cancer is normalcy of a sort. Cancer cells are “hyperactive, survival-endowed, scrappy, fecund, inventive copies of ourselves,” he says, and adds: “We can rid ourselves of cancer, then, only as much as we can rid ourselves of the processes in our physiology that depend on growth — aging, regeneration, healing, reproduction.”

Dr. Mukherjee grew up in New Delhi; his father was a manager for Mitsubishi, and his mother had been a schoolteacher. He went to a Roman Catholic school there, where he was required to learn by heart a staggering amount of poetry, but attended college at Stanford, which he chose mostly because some cousins lived in California. After studying immunology at Oxford on a Rhodes scholarship, he went to Harvard Medical School.

By the time he got there, Dr. Mukherjee had pretty much decided to specialize in oncology, but the experience of actually encountering patients was transforming. “All of a sudden it’s as if the world had turned,” he said. “Everything suddenly becomes real, and your emotional responses become hyper-acute.”

And it was because of a patient, he added, that he began to write “The Emperor of All Maladies.” “I was having a conversation with a patient who had stomach cancer,” he recalled, “and she said, ‘I’m willing to go on fighting, but I need to know what it is that I’m battling.’ It was an embarrassing moment. I couldn’t answer her, and I couldn’t point her to a book that would. Answering her question — that was the urgency that drove me, really. The book was written because it wasn’t there.”

He wrote most of it in bed, propped up on pillows, and by mastering what he called the “art of full indiscipline.”

“Instead of saying, ‘I’ll get up every day at 5:30’ or, ‘I’ll write from 9 to 12,’ I did the complete opposite,” he said. “I said: ‘I will write during the day for 5 minutes, 10 minutes, whatever. I’ll write in stretches until the book is done.”

“The Emperor of All Maladies” (which Dr. Mukherjee adapted into an article for The New York Times Magazine last month) employs a complicated structure, looping around in time, juggling several themes at once and toggling between scientific discussions and stories of people, and yet Dr. Mukherjee says he wrote it in pretty much linear fashion from start to finish, without moving things around. He was influenced by both Richard Rhodes’s study “The Making of the Atomic Bomb” and Randy Shilts’s “And the Band Played On,” each a big book about a historical moment, but his real breakthrough came, he said, when he conceived of his book as a biography.

“I began wondering, can one really write a biography of an illness?” he said. “But I found myself thinking of cancer as this character that has lived for 4,000 years, and I wanted to know what was its birth, what is its mind, its personality, its psyche?” At times in the book he even personifies the illness, talking about its “saturnine” quality, its “moody, volcanic unpredictability.”

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Last week Dr. Mukherjee gave an upbeat lunchtime talk to a group of cancer fellows at Columbia, young physicians who are preparing to become oncologists. He spoke quickly, clicking through a series of PowerPoint slides, but occasionally slowed down to remind the fellows about the kinds of questions that were bound to come up in their board exam. Talking about drug treatments, he reminded them: “If something is good, more is not necessarily better. Not always.”

“Are cancer patients living longer?” he asked, and then answered his own question: it depends on which cancer and on when you start measuring. And yet in the treatment of myeloma, his main theme that day, changes had come so fast, he said, that everything he had learned at their age was already out of date, and a new generation of drugs — über-thalidomides, he called them — were changing the picture even as he spoke. Myeloma, a cancer of blood plasma cells, is still not curable but often now is very treatable.

Dr. David Scadden, a Harvard hematologist and oncologist who supervised Dr. Mukherjee when he was a cancer fellow, recalled that his enthusiasm was such that he sometimes seemed to levitate off the laboratory floor. “People who take care of cancer patients and also have the research dimension are people who are unsatisfied with how things are but optimistic about how they might be,” he said. “Sid has an internal hope machine.”

At one point in “The Emperor of All Maladies” Dr. Mukherjee calls oncology a “dismal discipline,” but, sitting in his office, he said his work did not make him feel dispirited. “What does it mean to be an oncologist?” he explained. “It means that you get to sit in at a moment of another person’s life that is so hyper-acute, and not just because they’re medically ill. It’s also a moment of hope and expectation and concern. It’s a moment when you get to erase everything that’s irrelevant and ask the most elemental questions — about survival, family, children, legacy.”

“Most days,” he added, “I go home and I feel rejuvenated. I feel ebullient.”

Courtesy: The New York Times

http://www.nytimes.com/2010/11/09/books/09mukherjee.html?pagewanted=2

 

Author Website

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http://sidmukherjee.com/

 

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