Our Shapeshifting Companion
- The Emperor of All Maladies: A Biography of Cancer by Siddhartha Mukherjee
Fourth Estate, 571 pp, £9.99, September 2011, ISBN 978 0 00 725092 9
Siddhartha Mukherjee is an oncologist, physician and laboratory scientist whose book captures the excitement of biomedical research and discovery, the wonder at the complexities of cancer and the bodies it inhabits, and the thrill of major advances in knowledge and practice. Mukherjee seldom dismisses older methods of treatment or those who promoted them, but his book is mostly about what they lacked and what future therapies promise.
Without a molecular framework for understanding cancer, he argues, doctors’ ability to intervene against this group of diseases was limited. The major methods of treatment employed before the 1990s were based on questionable premises and used the bluntest of tools: surgery, carried out on the assumption that cancer began locally before affecting other parts of the body; and radiotherapy and chemotherapy, on the assumption that cancers comprise cells that divide more rapidly than the surrounding normal ones. All of this changed with a series of exhilarating breakthroughs in the last decades of the 20th century. Scientists discovered proto-oncogenes and tumour suppressor genes, which either accelerate or inhibit tumour growth, acting as ‘jammed accelerators’ or ‘missing brakes’, as Mukherjee puts it. They learned about the dependence of cancer cells on permanently activated signalling pathways which drive them to divide and grow, and about the capacity of cancer cells to resist death signals, and to metastasise throughout the body. They also came to understand how tumours grow their own blood supplies, making use of the pathways used when blood vessels are formed to heal wounds. These discoveries opened up a new world of so-called targeted therapy.
Without such targets, Mukherjee suggests, physicians’ interventions had been crude. In the late 19th century, the Johns Hopkins surgeon William Stewart Halsted pioneered radical forms of mastectomy, shunning what he called ‘mistaken kindness’ in favour of removing not only the breast but much, much more. The key to successful treatment, he believed, was to remove the tumour while it was still localised, before it spread to other parts of the body and the chances of successful treatment disappeared. Halsted was not the first to see cancer as a local lesion that later spread. The problem was that even after surgery many cancers recurred, sometimes at the fringe of the excision. Halsted took this to mean that surgeons did not remove enough: cancer cells remained in the body, the seeds of future tumours, sometimes spread by surgeons themselves. His solution was to cut deeper and farther, removing not only the breast but also the skin, neighbouring lymph nodes, muscles and, at times, parts of the ribcage or shoulder. Mukherjee argues that Halsted’s approach was too radical for those patients in whom the disease remained local, and too conservative for those in whom it had spread. Yet radical approaches dominated cancer surgery for much of the 20th century. Halsted’s former students populated leading American hospitals and trained students in this approach, while surgeons cut ever deeper and wider.
The New York surgeon George Pack – Pack the Knife – gained a reputation for aggressive surgery in the 1930s when he upset the conventional wisdom that stomach cancer was untreatable by performing a total gastrectomy (the removal of the entire stomach), and then a total extended gastrectomy, which removed the spleen and pancreas in addition to the stomach. There followed scapulothoracic amputations (the separation of the collarbone, shoulder blade and arm, gruesomely labelled the ‘fore quarter’), hemipelvectomies (in which a leg and an adjacent bone from the pelvis were removed, labelled the ‘hind quarter’), and operations for cancers of the oesophagus, pancreas, spleen, colon and liver (he removed up to 80 per cent of the liver).
Pack was not alone in his enthusiasm for such radical operations. Bolstered by wartime improvements in anaesthesia and blood transfusion, and the development of antibiotics, other physicians joined the bandwagon in the 1950s and 1960s. Despite favourable media coverage of these interventions, there was a worry that such radical surgery generated as much fear among the public as the disease itself and led people to delay seeking medical help. American cancer campaigns in the 1950s sought to reassure the public about the effectiveness of surgery and to manage fear of the disease and its treatment. But it still remained difficult to persuade people to undergo surgery, with patients feeling they were deciding between a painful and deadly disease and a painful and mutilating operation.
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