The Emperor of All Maladies
Siddhartha Mukherjee’s The Emperor of all Maladies brings the rich details of the biography of cancer into sharp relief. His intense, sometimes overwhelming history of cancer describes the commonplace particulars that make up a patient’s memories of illness, never forgetting the pain of each new diagnosis.
He begins his story by describing one patient, thirty-year-old kindergarten teacher Carla Reed. She wakes with a numbing headache, suffers from white gums, bruises on her back, and exhaustion. When the nurse calls her for another blood draw, Carla remembers “the clock, the car pool, the children, a tube of pale blood, a missed shower, the fish in the sun (in her shopping basket threatening to spoil), the tightening tone of a voice on the phone… “‘Come now’ she thinks the nurse said, ‘Come now’.” She finally learns her diagnosis after weeks of guesswork and the proper blood tests: acute lymphoblastic leukemia.
Mukherjee continues his journey through the 4,000-year history of cancer, drawing us into the drama of each patient, each step forward in research, reminding us of the impact of this disease on patients, families, friends, researchers, and medical staff, as well as the prayerful hope of a cure, any cure of cancer. The difficulty of this quest is that “cancer is not one disease, but many diseases. We call them all ‘cancer’ because they share a fundamental feature: the abnormal growth of cells.”
He beckons us back to when cancer was likely first recorded. Imhotep, an Egyptian physician who lived around 2525 BC, described a case of a “bulging mass in the breast” which is cool, hard and dense as an “unripe hemat fruit.” We learn of Arthur Aufderheide, a professor at the University of Minnesota in Duluth and paleopathologist who discovered cancers in mummified specimens.
Mukherjee points out that “the most striking finding is not that cancer existed in the distant past, but that it was fleetingly rare.” He explains that cancer is an age-related disease. Nineteenth-century doctors often linked cancer to civilization. In their imagination, modern life somehow incited pathological growth in the body. However, “civilization did not cause cancer, but by extending human life spans — civilization merely unveiled it.”
The history of cancer treatments coincides with the history of medical advancements: accurate anatomical descriptions that laid the foundation for the surgical extractions of tumors, anesthesia that allowed surgeons to perform prolonged operations, the creation of antiseptics, and the development of radical surgeries performed in the hope of curing breast cancer. Mukherjee describes the struggle of radiation medicine against its inherent limits, including its ineffectiveness against metastasized cancer and that radiation itself could produce cancers.
Mukherjee connects chemotherapy to sixteenth century physician Paracelsus’ opinion that every drug is a poison in disguise. If so, then cancer chemotherapy had its roots in the obverse logic that every poison might be a drug in disguise. Chemotherapy research grew from the discovery that mustard gas, used during World War I, targeted bone marrow and wiped out only certain populations of cells, thus leading to an experiment to target malignant white cells.
He tells us the story of Sidney Farber, a pediatric pathologist in 1947, who hoped to halt the growth of leukemia in children with the yellow crystalline chemical aminopterin. To obtain more research funds, Farber dreamed of creating a fundraiser for leukemia similar to March of Dimes for polio research. To this aim, his patient Einar Gustafson, a “lanky, cherubic, blue-eyed, blond child” was rechristened Jimmy and marketed to America on the radio show Truth or Consequences on May 22, 1948.
After interviewing Jimmy on the air, host Ralph Edwards encouraged the listening public to think of Jimmy as a representative for the thousands of boys and girls suffering from cancer. Research funds were needed to help find a cure. $231,000 was raised for the Jimmy Fund, in turn giving much-needed publicity for cancer research.
Mukherjee details decades of chemotherapy’s trial-and-error approach. He describes Brian Druker’s work in the later 1980s with kinase-specific inhibitors. Druker was drawn to oncology after reading Farber’s original paper on aminopterin. He realized that Farber failed because the mechanistic understanding of cancer was poor at that time. “Farber had the right idea, but at the wrong time.” Druker came up with the right idea at the right time with Nick Lydon in the development of Gleevec for the treatment of chronic myelogenous leukemia or CML.
The development of Gleevec paralleled the creation of patient chat rooms on the Internet, spreading news of the drug quickly, reports Mukherjee. By 1999 patients were exchanging clinical trial information online. In many cases, patients informed their doctors about Druker’s drug. When their doctors seemed unaware of this advancement, patients enrolled themselves in the Gleevec trial.
“Before the year 2000, CML was fatal, but now patients will usually live their functional life span if they take the oral medication Gleevec for the rest of their lives,” said Hagop Kantarjian, leukemia physician at MD Anderson Cancer Center in Texas. However, some patients found that cancer cells became drug-resistant, necessitating the creation of second-generation drugs as detailed by Mukherjee.
Mukherjee’s history leads us through antihormone therapy, adjuvant therapy, palliative care, and cancer prevention. Because cancer is actually a variety of diseases, he explains, no single approach will work. Oncology turned away from universal solutions and radical cures and back to understanding fundamental mechanisms of the cancer cell and focusing on cancer-causing genes.
In 1998, the mascot of Farber’s fundraiser efforts, Jimmy — Einar Gustafson was still alive. Fifty years later he returned to tour the Jimmy Fund building. Mukherjee speculates that it is impossible to know whether he survived because of surgery, chemotherapy, or that his cancer was inherently benign, but he returned as “the icon of a man beyond cancer.”
Mukherjee’s patient Carla Reed also survives her cancer. “My friends often asked me whether I felt as if my life was somehow made abnormal by my disease. I would tell them the same thing: for someone who is sick, this is their new normal.”
His biography of cancer concludes with the description of efforts to sequence the cancer genome. Once mutations have been identified, mutant genes will need to be assigned functions in cellular physiology. “We will need to move through a renewed cycle…from anatomy to physiology to therapeutics,” said Mukherjee.
The second new direction is cancer prevention, reports Mukherjee, including the link between nutrition and the risk of particular forms of cancer. He concludes with the sobering thought that cancer may become our “new normal” as cancer statistics change from one in four to one in three to one in two. He speculates, “the question then will not be if we will encounter this immortal illness in our lives, but when.”
While this biography is disturbing in its speculation that incidents of cancer will increase, I was heartened by Mukherjee’s many examples of the indomitable human spirit as we continue to face this illness through research, through inspiration of overcoming this disease, and the courage of patients and their medical staff.
Rochester Methodist Hospital
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