Wednesday 8 June 2011

The Emperor of All Maladies

From the occasional book review series - Siddartha Mukherjee's The Emperor of All Maladies.


Siddhartha Mukherjee is a writer/physician in the traditional of Oliver Sacks and Atul Gawande; in 'The Emperor of All Maladies', he binds together stories of the patients he treats as an oncologist in Boston with the history of the understanding and treatment of cancer.

The book opens with Carla, a 34-year-old kindergarten teacher who for the past month had been noticing increasingly concerning and painful symptoms - mysterious bruises, pale gums, exhaustion, a sudden and numbing headache on waking. She goes to her doctor for bloodtests; when her blood is drawn, is isn't red, but a thin, pale serum.

Mukherjee first hears about Carla when a sentence flickers up on his pager: Carla Reed / New patient with leukemia / 14th floor / Please see as soon as you arrive. Carla is whirled immediately into an isolated, sterilised room, and her five-year 'battle' with cancer begins. [I'm just going to be up front here - although I understand the history of the metaphor of cancer as a war, and survivors as ... well, survivors, it's still a metaphor I find distasteful.] We are returned to Carla throughout the book, and its conclusion coincides with her remission.

Between the beginning and end of Carla's story, Mukerjee takes us through 500 pages and 4,500 years of sickness, scientific discovery, political lobbying, fundraising, outsized personalities and bucketloads of factual trivia. Leukemia - the cancer Carla was diagnosed with - is regularly returned to throughout the book; the modern treatment of cancer began in the 1940s with Sidney Farber, a specialist in pediatric pathology (children's diseases), who decided to focus his attention on childhood leukemia: virulent, mysterious, almost inevitably fatal, but - almost magically, from a research point of view - a cancer that could be measured, and the efficacy of treatment revealed with data.

At Boston's Children's Hospital, Farber trialled treating children with leukemia with folic acid (which had recently been shown to restore the normal creation of blood cells in bone marrow in nutrient-deprived treatment). His first experiments went horribly wrong; folic acid accelerated the progression of leukemia in the children. But Farber was fascinated - if folate exacerbated leukemia, might an anti-folate treat it?

And there you have it - in one paragraph. Up until about the 1980s, treating cancer was a practice of ideas (not even what I would term theories) and experiments. From the 1950s, through the partnership of Farber (whose later experiments worked out much better than the first folate trial) and philanthropist Mary Lasker, America's Congress and private patrons funded the war on cancer on a basis Farber and Laskey deliberately compared to the Manhattan Project. But for decades, funding went primarily to trials, and only a snippet to research into prevention and the cellular basis of cancer - the basic research required for coherent, systematic development of targeted drugs.

The first half of Mukherjee's book is fantastic, fascinating and appalling. We move from the Egyptian physician Imhotep in 2,500BC, who categorised tumours, to Galen, to the hubristic surgeon heroes in the first decades of the 1900s. I was particularly struck and distressed by the story of surgeon William Halsted, who invented the radical mastectomy. Halstead worked from the thesis that cancer spread of radially from a central node, and that by excising all flesh that could possibly be infected, a relapse could be prevented. Surgeons cut deeper and deeper, further and further into women - removing breasts, chest and back muscles, lymph nodes, collarbones. Of course Halstead and his followers did not recognise that cancer metastasizes unpredictably; it may not reappear next to its first appearance in the breast, but in the liver, pancreas, brain. This may seem exploitative, but as Mukherjee writes:

When for patients, that manic diligence had become a form of therapy. Women wrote to their surgeons in admiration and awe, begging them not to spare their surgical extirpations, as if surgery were an analogical ritual that would simultaneously rid them of cancer and uplift them into health. Haagensen transformed from surgeon to shaman: "To some extent," he wrote about his patients, "no doubt, they transfer the burden [of their disease] to me." Another surgeon wrote - chillingly - that he sometimes "operated on cancer of the breast solely for its effect on morale."

When a surgeon named Keynes successfully trialled a treatment for breast cancer in the 1920s where the tumour was removed in a lumpectomy and then the patient treated with radiation at relatively low doses, he was laughed off, even though his remission rates were at least equal to extreme surgery. It's these kinds of stories - like that of the history of lobotomies - that chill me to the bone.

The second half of 'The Emperor of All Maladies' drags a bit in comparison. His chapters on the tobacco industry and the link between smoking and cancer are terrific, and filled with grim details. Smoking became so prevalent it was impossible to see it as being related to cancer. In 1870, cigarette consumption in America was under one cigarette per capita per year. In 1900, Americans consumed 3.5 billion cigarettes and 6 billion cigars a year. By 1953, the average adult American smoked ten cigarettes a day, the Englishman 12, a Scotsman nearly 20. In the 1920s, a renowned St Louis surgeon was asked whether tobacco smoking had caused the increased incidence of lung cancer, he replied 'So has the use of nylon stockings.' In an awful irony, at the same time researchers and surgeons were getting to grips with cancer treatment in the 1970s and 1980s, and quadrillions of dollars had been spent on the war on cancer, the incidence and mortality of cancer was increasing, as first the peaks of male and then female smoking came of cancer age. But in general, as the treatment and research into cancer become more detailed, so does Mukherjee's book, and I occasionally got lost or skimmed the odd page.

Mukherjee's writing is clear, even lyrical in admittedly odd places:

To choose a medical specialty is also to choose its cardinal bodily liquid. Hematologists have blood. Hepatologists have bile. Huggins had prostatic fluid: a runny, straw-coloured mixture of sugar and salt meant to lubricate and nourish sperm.

One small criticism relates to what I started calling the adjective trifecta: sentences like this appeared more than seemed necessary:

Impatient, aggressive, and goal-driven, the president, Richard Milhous Nixon, was inherently partial to impatient, aggressive, and goal-driven projects.

While my initial enthusiasm for the book didn't last all the way to the end, my admiration for Mukherjee remains. You can't help but look up to someone who can both practice medicine, and research and write a book like this.

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