The Emperor of All Maladies, a review

S. Mukherjee, The Emperor of All Maladies, 2010. A review.

This is a large book. There are nearly 600 pages, including a 26-page index, 59 pages of notes, and a select bibliography. Nonetheless, it is a lively book with prose at times more purple than common in nonfiction writing. The subtitle calls it "A Biography of Cancer." It is well-informed in the history of many branches of medicine as well as bravely philosophical in its inquiries.

It tells of the many forms of cancer from the point of view of an oncologist (S. Mukherjee, B.S. 1993, Stanford, D.Phil. 1997, Magdalen College, M.D. 2000, Harvard). As he treats his patients, he asks: where are we in the war against cancer? how did we get here? is there an end? can this war be won? 

Often, the first person voice of a doctor tells of an individual patient, such as Carla, a 30-year-old kindergarten teacher, and mother of three. On May 19, 2004, she asked her doctor to perform tests that might explain a month of worsening headaches, bruises, and lethargy. A lab assistant noted her blood looked watery, pale, and diluted. She was diagnosed in a few days as suffering from “acute lymphoblastic leukemia … a special incarnation of cancer [with] its pace, its acuity, its breathtaking, inexorable arc of growth …” But in 30% of cases, it was curable.

Mukherjee next skips back 57 years to 1947, and starts the story of Sidney Farber, a pediatric pathologist who then conceived of using chemicals in “therapeutic intervention” – chemotherapy. The author next goes back a whole century to 1845 and the autopsy of a slate-layer by John Bennett a Scottish doctor that revealed the patient's blood, full of pus but no sign of infection. Bennett speculated whether or not there had been a “spontaneous suppuration.” 

The author then describes the work R. Virchow, a German doctor familiar with Bennet’s work. Virchow renamed the illness weiss blut – leukemia. Like the Greeks who believed that philosophy began when things were given their proper names, Mukherjee zeroes in on the importance of Virchow’s achievement. The correct naming of this and other forms of cancer was important in bringing focus to the analysis of the disease, which by the end of the nineteenth century led to a study of the cells in a patient’s body. 

This insight was important to frame Farber’s astounding work. Concentrating on human cells, Farber explored the chemistry of cell growth: what quickened cell growth or retarded it? Would some chemical analogy work on diseased cells? If science was founded on measurement, then Farber and his team surely proceeded on scientific ground, measuring every detail - blood count, transfusion, fever, etc. The researchers narrowed in on the complex vitamin B12 and variations of folic acid critical for the growth and development of normal cells. How would they affect the growth and development of cancer cells? They tracked the treatment of twins and pursued therapies even if one twin did not respond as well as the other.

They observed that several patients experienced partial remissions before succumbing to a variation of their illness. Cancer cells not only multiplied to overwhelm the bodies of their victims, but when checked by one or another of the drugs Farber and his team used, appeared to regroup and multiply again. The cells mutated spontaneously and evolved by the same mechanism that enabled life on earth to develop—natural selection. 

Observing late in the nineteenth century that the removal of breast cancer tumors often resulted in the reappearance of the disease elsewhere had led William Halsted to invent and refine the radical mastectomy. (The brutality implicit in the elaboration of this therapeutic pathway had a pale reflection in that pursued for prostate cancer.) 

Radiation therapy would not be widely accepted until after the work of Pierre and Marie Curie in the early 20th century - after their exposure to radioactive material showed that radiation could not only cure cancer but also cause it.

The chemotherapy that Farber pioneered inspired Min Chiu Li and Roy Hertz when they faced patients suffering from cancer of the placenta. Li, in particular, became obsessed with treating his patients even when their cancer appeared to have been eliminated. Li wanted to pursue the chemotherapy until the blood show absolutely no trace of the hormone that diseased cells secrete. He ignored the toxicity of the therapy to the patient and thus was fired. Not until five years later was it found that in the patients he had treated to the point of zero, there were no relapses. He had unwittingly achieved the first chemotherapeutic cure of cancer in adults.

Farber’s work on antifolates won him fame in the 1940s and 50s. He also grasped that much of the war on cancer needed to be waged outside hospitals and labs. To arouse a reluctant nation to support research into cancer required a political crusade. He teamed up with Albert and Mary Lasker, philanthropists. "To Farber's evangelistic tambourine, [Mary] Lasker added her own drumbeats of enthusiasm."

The doctor championed cancer research and one of his patients, Einar Gustafson was renamed Jimmy for what became the Jimmy Fund. The Farber–Lasker combination brought together political lobbyists and a strategist well-informed in the science. The team visited Congress regularly to lobby for funds for cancer research.

A major achievement of Mukherjee’s book is that to the fluent description of the doctors, patients, cancers, and cures he brought also an alert perception of the sociopolitical environment. As the March of Dimes gave a great boost to medical and cancer research, so the tobacco industry sought to thwart public health efforts against smoking. It rested its case ultimately on the contention science did not show that smoking caused cancer. [This was not the last time a basic requirement of hard science was used to thwart public health policy.] 

The search for a cause, a virus, or germ that could be exhibited as the origin of cancer might have foundered on semantics. Could there be an exogamous cause for a disease that sprang from endogamous mutation? Broad history was anecdotal: during the nineteenth century, cancer of the alimentary tract was widespread, ‘no doubt’ due to poor (misunderstood) hygiene; in the twentieth century, lung cancer was undeniably rampant, was this the result of cigarettes being given to soldiers in the world wars to boost morale?

The author shows how relevant statistics can be collected. The introduction of the national health system in the UK in 1948 required a registration of 40,000 doctors. Their death statistics shed perhaps helpful light. Between 1951 and 1954, for instance, 36 doctors died of lung cancer. Every one of them had smoked.

The debate over the cause of lung cancer continued in the US. In 1965, Bradford Hill, enunciated principles to guide epidemiologist to show a connection between possible cause and effect: was the relationship strong, was it consistent, specific, plausible, coherent, did it increase with time or 'biological gradient'? That same year, Congress passed the act requiring the label, “Caution: cigarette smoking may be hazardous to your health.”

Halfway through the book, the author quotes William Carlos Williams, “If a man dies, it is because death has first possessed his imagination” to introduce the work of an oncologist in “repossessing” his patients’ imagination from death. It demanded an act of “exquisite measuring,” for too much and “imagination might bloat into delusion” while too little “might asphyxiate hope altogether.”

Such was the case with Susan Sonntag whose first doctor was “totally pessimistic.” (Her story was captured by her son’s memoir.) She battled for months to find a doctor “whose attitude was vastly more measured and who was willing to negotiate with her psyche.” Of the clinicians that the author trained with, Thomas Lynch, who treated lung cancer patients was such a master of “medical nuance.” He recognized that a patient who had survived the removal of a large lung mass was “catatonic with fear.” The doctor spent an hour talking about the surgery, her family, and a grandchild nearby, before broaching the subject of recurrence or metastasis, perhaps even a fifty or sixty percent chance. There are ways, Lynch said, “that we will tend to it when that happens.” When not if, care not cure.

How does an author of a biography end a book in which the subject seems far from being terminated? When Mukherjee began the book, he thought it might have ended with Carla’s relapse and death, but no. She had undergone five years of chemotherapy without a relapse, which meant she was as close to cured as she could be. So he closes with Atossa, a Persian queen who was diagnosed with what was most likely breast cancer. With her case in mind, he recapitulates the treatments/cures that have been developed since 500 BC. Mastectomy, radiation, chemotherapy, genetic sequencing, and targeted drugs – not so much curing the disease as prolonging life. The scientist is hopeful, the doctor is philosophical.

The Emperor of All Maladies won the Pulitzer Prize in 2011 and was made into a PBS miniseries in 2015.