A U.S. Public Health Services poster warns against medical fraud, c. 1940s. National Library of Medicine.
“To understand a cancer cell, you have to be that cancer cell.” This Zen declaration, attributed to Nobelist Barbara McClintock, demands that the malign persona of cancer be penetrated in order to better know its devious character.
Siddhartha Mukherjee imbues his superb history of cancer, its origins, treatment, and impact on society with a similar philosophy. In The Emperor of All Maladies, Mukherjee, a young practicing clinician and researcher, provides an immensely readable account of the stumbling attempts to understand and master a disease that—directly or indirectly—touches us all. His page-turning scientific and clinical story is infused by accounts of his own sometimes bleak and sometimes ecstatic experiences with patients, and provides the essential human perspective to a story about an incredibly complicated set of diseases, their molecular pathology, and their impact on society.
For patients struggling with fear, fatalism, and frustration after a cancer diagnosis, who feel isolated in an uncertain world with their disease, this book provides a sympathetic and honest account of what cancer is and what the frontiers and limitations of knowledge are. Though his approach is scholarly, Mukherjee never loses sight of the patient or the dedicated human effort and the buzz of optimism felt by cancer researchers and clinicians. His narrative of spectacular advances is accompanied by failures and disappointing retreats from scientific cul-de-sacs. And, ultimately, it provides a text of hope: in the past 50 years progress has been spectacular, though Mukherjee recognizes that metastatic disease in the majority of cancers remains a challenge. This progress is not in treatment alone, as the author shows by chronicling our improved understanding of the causes of many cancers and thus how they may be avoided. Understanding the basis of the mutagenic and carcinogenic properties of some chemicals has changed habits both in the laboratory and society. His spellbinding account of Austin Bradford Hill and Richard Doll’s epidemiological work linking cigarette smoking to lung cancer is wonderfully written. He is rightly damning of the cynicism of the tobacco lobby and its continued worldwide pursuit of the vulnerable.
Mukherjee seems most at ease in his section “Prevention Is the Cure.” The author emphasizes the roles of many mavericks of science and medicine, making them the central, enthralling characters in this unfolding story of cancer, its prevention, and its treatment. Poor émigré pathologist George Papanicolaou stared obsessively—“with monastic ferocity” (p. 288)—at changes in the cytology of hamster cervical cells. After extending this focus to the detection of cervical lesions in women, he was ridiculed. The Pap smear was instigated decades after his initial observations and has since saved innumerable lives. Likewise, the sobering account of William Halstead’s school of total mastectomy, which needlessly butchered countless women, is both a case in point and an enthralling and blood-chilling account of an aggressive protocol that developed enough momentum to escape scrutiny. Throughout this compelling history of research and discovery the author rightly highlights how difficult it was—and sadly remains—to overthrow accepted dogma, particularly when associated with dominant personalities.
Inertia in cancer research, particularly the translation of new findings to the clinic, occurs despite medical need and the emergence of new knowledge. This inertia is a secondary theme weaving through a narrative that vividly recalls the landmarks of success. An element of this inertia (partially neglected in this otherwise excellent work) is the disconnect between various disciplines. For example, regardless of the clear limits of drugs that also kill normal proliferating cells—used by warrior clinicians in aggressive protocols—medicinal chemists were slow to stop synthesizing nonspecific poisons, despite the emerging molecular-pathology insights of the 1980s and 1990s. Instead of designing molecules that would target changes unique to cancer biochemistry, chemists’ love affairs with the often complex chemistry of potent toxins led to a philosophy that “interesting chemistry gives rise to interesting biology.” The result was a plateau in drug discovery in the last decades of the 20th century. Only later did the benefits of an integrated, multidisciplinary team become obvious: the translation of biological findings into therapeutic benefit depends on creative chemists, aided by structural biologists, synthesizing smart molecules. To illustrate this point, Mukherjee nicely recounts the triumph of the multidisciplinary Novartis team, which worked with a tenacious clinician, Brian Druker, in the discovery of Gleevec. This drug has transformed the treatment and outcome of chronic myelogenous leukemia and laid the basis for the discovery of therapies targeting biochemical changes unique to cancer cells.
For scientists, the multidisciplinary teamwork required for progress in cancer demands that team members understand the culture and history of their colleagues. The Emperor of All Maladies, with its flowing narrative and easy, sometimes poetic style, provides the perfect primer. But this book is also for anyone who has been touched by cancer.
John Hickman is former ICI Professor of Molecular Pharmacology at the University of Manchester and was the director of cancer drug discovery at Servier. He currently coordinates a large research consortium supported by the European Union's Innovative Medicines Initiative, a biotech-academic collaboration that ams to optimize drug discovery.