Siddhartha Mukherjee’s The Emperor Of All Maladies

How is this for a resume? Siddhartha Mukherjee has degrees from Oxford, Stanford and Harvard; won a Rhodes scholarship; teaches and does research at Columbia University; and won a Pulitzer Prize for his 2010 “biography” of cancer, The Emperor Of All Maladies. All of this, and yet he’s still three years shy of his fiftieth birthday. In a fairer world, so much talent and accomplishment encompassed in one man would be illegal, but in this world we can be grateful for his industry. Mukherjee’s speciality within medicine is oncology and hematology – the study of cancer and the study of blood-related diseases, which makes him an ideal candidate to offer a history of cancer and our centuries-long battle against it.

The Emperor Of All Maladies reads, in part, like a detective novel, with cancer cast as the elusive villain – a role for which it is well-suited. For most of human history, Mukherjee impresses upon us, cancer was largely hidden from view, overshadowed by more fatal diseases such as Polio and tuberculosis. This is the first of cancer’s many paradoxes: our very longevity has made it prominent. In the West, for example, about one person in four hundred will be diagnosed with cancer before their 30th birthday, but that number rises to one in six by the age of 65. Another cancer paradox: the better we get at treating it, the more prevalent it becomes, since cancers that once carried a prognosis of months can now be battled to a stalemate or forced into remission. Mukherjee traces the history of cancer, from its earliest mention in an Egyptian hieroglyph, attributed to the polymath and physician Imhotep, to the advent, in the 19th century, of surgeries designed to excise the malignancy, to latter-day chemotherapies and pharmaceutical cocktails. Every development in the battle against cancer was accompanied by a shift in the medical paradigm of the times, usually by some advancement of our understanding of human anatomy, and this I found particularly fascinating, because I was accustomed to thinking that the study of medical history  – particularly prior to, say, the discovery of the circulatory system – was largely obsolete, given how much our understanding has expanded even in the last century. Mukherjee, donning his scientist’s cap, insists otherwise: “Scientists often study the past as obsessively as historians because few other professions depend so acutely on it. Every experiment is a conversation with a prior experiment, every new theory a refutation of the old.” There is value in error, after all, since every mistake properly considered is just one wrong answer eliminated from further consideration. Of course, in medicine, mistakes have deadly consequences, and part of the tightrope Mukherjee walks in this book is balancing the science of cancer with its devastating human impact.

Consider the earliest breast cancer surgeries. At a certain point, a surgeon made the observation that the more tissue he removed, the better the chance his patients had at long-term survival. It didn’t hold true in every case, but often enough that a gruesome logic took hold: when confronted with breast cancer, it is better to err on the side of caution and remove as much as possible: muscle, tendon, fatty tissue, glands – even the lymph nodes beneath the armpits. The pioneer of this “radical mastectomy” was William Stewart Halsted, and his meagre results were enough to encourage surgeons on both sides of the Atlantic to follow suit, with even more zeal: ribs were sometimes removed, shoulders amputated, collarbones disappeared. The consequences of such surgical exuberance were permanently disfiguring:

With the pectoralis major cut off, the shoulders caved inward as if in a perpetual shrug, making it impossible to move the arm forward or sideways. Removing the lymph nodes under the armpit often disrupted the flow of lymph, causing the arm to swell up with accumulated fluid like an elephant’s leg, a condition vividly called “surgical elephantiasis.” Recuperation from surgery often took patients months, even years.

To the disgrace of these surgeons, and the medical community at large, it took years before their methods were put to a simple efficacy test: did the radical mastectomy reduce cancer deaths, and did it do so in a large enough percentage of cases to justify its ghastly price? The answer was no, for reasons that would not be made clear until the nature of cancer came into focus. If a patient arrived before William Halsted with a late-stage cancer – one that had spread from its point of origin throughout the body – then no amount of surgery would suffice. If, on the other hand, the patient arrived early enough that their cancer was still localized, then a small extraction rather than a radical surgery would be sufficient.

Fast forward to the 1950s, when cancer treatment had advanced from disfiguring surgery to the all-purpose poison of chemotherapy, whose logic can be simply summed up: the doctors will inject you with controlled doses of a lethal poison, hoping that your cancer will succumb before you do. In the fall of 1956, a Chinese national working on cancer research in the United States, Min Chiu Li, focused in on a rare form of cancer, choriocarcinoma, which forms from an abnormal growth in the placenta during pregnancy and rapidly metastasizes into a lethal malignancy. Choriocarcinoma, it turns out, is unusually responsive to chemotherapy, and for the first time in medical history, Li witnessed a “metastatic, solid cancer vanish with chemotherapy.” While his patients counted their blessings and his peers cheered, Li remained skeptical.

[…]there was a glitch in all this – an observation so minor that it could easily have been brushed away Choriocarcinoma cells secrete a marker, a hormone called choriogonadotropin, a protein that can be measured with an extremely sensitive test in the blood[…]. Early in his experiments, Li had decided that he would use that hormone level to track the course of the cancer as it responded to methotrexate. The hcg level, as it was called, would be a surrogate for the cancer, its fingerprint in the blood. The trouble was, at the end of the scheduled chemotherapy, the hcg level had fallen to an almost negligible value, but to Li’s annoyance, it hadn’t gone all the way to normal. He measured and remeasured it in his laboratory weekly, but it persisted, a pip-squeak of an umber that wouldn’t go away.

His disquiet at this trace markers led him to do something unheard of in cancer treatment thus far: Li ordered his patients to continue on their chemotherapy, long after the visible signs of cancer had disappeared. To the medical establishment, this was nothing less than barbarism, the unnecessary prolongation of a poisonous treatment, tantamount to unauthorized medical experimentation; Li was promptly summoned before the National Cancer Institute and dismissed. It would take years for Li to be vindicated: the patients he continued to treat lived on, while those who prematurely ceased treatment inevitably suffered a remission. As Mukherjee puts it, “Li had stumbled on a deep and fundamental principle of oncology: cancer needed to be systematically treated long after every visible sign of it had vanished.” This was a paradigm-shifting discovery, one that arrived humiliatingly late in our study of cancer.

The Emperor Of All Maladies contains within it not only a history of cancer, but of our efforts – medical, societal, governmental, and legal – to combat it, and these elements are all equally fascinating. Take, for example, the discovery of carcinogens. London’s famous chimney sweepers – orphan boys, often just five years old, who were stripped almost naked and sent up the soot-filled chimneys of England to sweep away the accumulated soot – led horrible lives, but when they did not succumb to their dangerous working conditions, many of them developed scrotal cancer, and a London surgeon, Percivall Pott, noted the connection between their employment and this rare tumor. Could there be something in the chimneys, some malignant element, causing cancer? The 20th century would provide the answer, but only after cancer epidemics caused by asbestos and a rise in cigarette smoking made the connection undeniable. And then, of course, knowing the causal relationship between, say, smoking and cancer was not enough, by itself, to curtail the public consumption of cigarettes, or prompt government action to regulate a highly profitable industry. Mukherjee covers all of this, and more, in limpid prose, writing a novelist would envy, which he can twist and shape to suit any purpose, from describing the intricacies of molecular biology in terms a layman can understand, to evoking the sombre mood of a palliative care wing, and the men and women forced into prematurely confronting their own mortality.