The Emperor of All Maladies

Title: The Emperor of All Maladies – A Biography of Cancer

Author: Siddhartha Mukherjee

Publisher:  Fourth Estate, 2011 (First)

ISBN: 978-0-00-742805-2

Pages: 470

Cancer – No other word terrorizes humanity harder than that. Often late to correctly diagnose, it snuffs life out of healthy individuals in the blink of an eye and drives the survivors into a lifetime of sorrow and misery. Though the disease was around and recognized for millennia, it was only after the Second World War that effective treatment regimen started to appear in the form of chemotherapy at first. Dr. Siddhartha Mukherjee, the author, is the right person to describe the biography of the dreaded disease, as he is a cancer physician and researcher. He is a Rhodes Scholar, and is now assistant professor of medicine at Columbia University and practices at the CU/NYU Presbyterian Hospital. He has published articles in Nature, The New England Journal of Medicine and The New Republic. The germ of the book was sown in him during his tenure as a post-doctoral fellow of oncology at the Massachusetts General Hospital – the legendary hospital where anesthesia was invented in 1846 and the centre of activity of many fictional medical thrillers.  During the course of his work, Dr. Mukherjee came across several patients who inexorably marched towards their deaths while the medical establishment stood silently by the wayside – in the full realization that nothing could be done to save those lives, except providing palliative care. This book is a noted one of its genre and has bagged several distinctions, including the Pulitzer Prize for non-fiction in 2011, and I’m sure the honours list won’t end with it.

Those people who blame modern lifestyle changes to the increased incidence of cancer may do well to remember that the dreaded disease is in fact very ancient. Imhotep, an ancient Egyptian physician who lived around 2650 BCE, records breast cancer with a comment that there was no available cure. Herodotus, the ancient Greek historian, narrates the case of Atossa, Persian queen and wife of the mighty emperor, Darius. She too developed breast cancer which was surgically removed by a Greek slave, Democedes. A grateful Atossa prompted her husband to turn his next aggressive campaign to the west instead of the east – to Greece – so that the homesick slave could return to his homeland. The resultant Graeco-Persian was a pivotal moment in world history – in fact, we may safely contend that the moment moulded the course of future history from then on, resulting in the fall of Persia and the campaigns of Alexander the Great. Thus, cancer, even as a clandestine illness, left its fingerprints on the ancient world. The incidence of cancer seems to have increased over the ages, because most of them affect us as we grow old. For a 30-year old woman to develop breast cancer, the odds are 1 in 400, whereas for a 70-year old, it is 1 in 9. So, along with growth in life expectancy, incidence of cancer increased, coinciding also with receding of other killers such as tuberculosis, small-pox, and plague. Advanced early detection techniques also contribute to the statistics of increased incidence.

It was in the time of Hippocrates, around 400 BCE, that a word for cancer first appeared in literature: karkinos, from the Greek word for ‘crab’. The tumour, with swollen blood vessels around it might have reminded Hippocrates of a crab dug in the sand with its legs spread in a circle. Another Greek word, onkos, which meant ‘a mass’, ‘load’, or ‘burden’, made an appearance. Onkos, or cancer was imagined to be a burden carried by the body, from which the discipline of oncology would take its modern name. The medieval dark ages remained dark for medicine too, and only with the Renaissance do we witness further improvements. Breakthroughs like anesthesia (1846) and antisepsis (1867) caused a proliferation of surgical procedures.

Cancer comes in diverse forms – breast, stomach, skin, leukemias and lymphomas. Of all these, blood cancer (leukemia) has captured the nervous attention of a whole generation of playwrights and writers of every sort to make an impression on the public mind that it is uncurable. Leukemia, which is the uncontrolled growth of white blood cells, was identified in 1850s by the German researcher Rudolph Virchow, who coined the term leukemia from the Greek leukos, meaning ‘white’. World War II was a watershed moment in the history of technology, as well as medicine. Just prior to the war, the cure for cancer consisted of one of two things, excising the tumour surgically or incinerating it with radiation – a choice between the hot ray and the cold knife! By 1940, it was sadly, yet widely acknowledged that therapeutics against cancer was at a dead end. Something revolutionary needed to come up.

And the revolutionary thing indeed turn up, in a quite unexpected quarter. Though professing otherwise, both the warring sides in the World War employed chemical warfare on their enemies. Of all the chemicals used, nothing was more fearsome or devastating as mustard gas. It killed immediately and the survivors were forced to lead miserable lives owing to complications like chronic anemia. Researchers detected that the poison gas destroyed white blood cells (WBC) in survivors and surmised that it could form a part of an effective treatment against leukemia (which increased white cell count) in controlled doses. In the meantime, Sydney Farber, an American physician was wondering in 1947 whether he could control the pathological growth of WBC, using a chemical. Folic acid, was found to cause growth of WBC in anemic people, so Farber argued that if he could lay hands on an anti-folate (a chemical which works in a diametrically opposite way than folic acid), it could be used as medicine for leukemic patients. He eventually came across such a chemical structurally similar to folic acid, called aminopterin, which he first tried on a child suffering from acute lymphoblastic leukemia, with good results. The age of chemotherapy was born! However, in most cases, the remission was only temporary with the patient relapsing irrevocably to recurred illness, which was resistant to further chemotherapy. The cancer also travelled to other parts of the body, like the lungs, liver, brain and bone marrow, which is called metastasis. Researchers struggled hard to find a wayout and they were finally rewarded – using multiple drugs in combination, a fixed percentage of cancerous cells would be obliterated. Repeating the course several times, the percentage of abnormal cells would be reduced to near zero.

However, the chemicals used as drugs in chemotherapy were cytotoxic (damaging to the cells), which destroyed healthy cells as well as the cancerous. The body reeled under the heavy doses of drugs, with severe side effects, one of them being leukemia itself, at a later stage. There was no way to distinguish the tumorous cells. The birth of linear accelerators in physics labs during the 1960s helped to incorporate that also in the war against cancer, in the form of extended-field radiation. Clinical trials helped modify or discard established procedures too. Radical mastectomy, the surgical removal of large parts of the chest was the common procedure for breast cancer at that time, till it was challenged by feminist groups and innovative surgeons. A trial which lasted 10 years conclusively proved that the radical one was not fundamentally different in efficacy from simpler, less invasive procedures.

Relapse of the disease, after a brief remission, was a nagging problem for chemotherapy. Patients returned with metastasized cancer, often ending up in brain. The malignant cells somehow crossed the blood-brain barrier, which stopped the chemicals. Attempts to transport the drugs directly to brain via cerebro-spinal fluid through spine taps were also not promising. It was around 1970s that the importance of prevention dawned upon the researchers. Lung cancer is highly preventable, if the afflicted stayed away from tobacco smoking. Concerted legal and public awareness campaigns helped to bring the tobacco industry to heel. They acknowledged the risks tobacco posed to public health and were forced to print warning labels on cigarette packs. Development of pap smear test for cervical cancer and mammography for breast cancers opened a window of screening, but none of them reached the level satisfactory to pronounce as such.

Knowledge of cancer biology improved drastically after 1980s. Cancer is the uncontrolled growth of normal body cells caused by mutations picked up genetically or environmentally by the normal genes. The genetic mechanism consist of two ways – to enable growth and to control growth after maturity of the cell is reached. Oncogenes, which are mutated growth genes contribute to unbridled growth, just like a jammed accelerator in a car. On the other hand, inactivity in the control genes also fail to stop growth, just like a non-functional brake in an automobile. Developments in recombinant DNA technology and genetic engineering helped device new drugs which could hook on to aberrant proteins at the molecular level and keep them under harness. Herceptin was the first such drug, but the wonder drug turned out to be Gleevec, which became a panacea for chronic myeloid leukemia (CML), a rare form of cancer. This medicine removed all traces of pathogens and enabled patients to continue their lives for decades. But, molecular medicine carries its own risks too. The cancer gets immune to the drug by accumulating mutations again. The race against it cannot be static – there is not a dull moment in researchers’ attempts to fight cancer.

The book is a comprehensive history of cancer, reaching out to the dawn of history to the latest developments in genetic drugs. It is also a history of the medical profession, beautifully unveiling the troubled pathways it traveled to possess the glowing feathers it carries now in its diadem. Using an eclectic mix of science and history, Mukherjee produces a long-awaited delicacy in the feast of medical books. The description is clear and lucid, attractive even to lay readers. The handling of the subject is so professional that this book should adorn the shelves of every medical practitioner, as well as serious admirers of the popular science genre. Insightful comments and dispassionate narrative brings out objective truths in the cold light of reason. It is interesting to note that chemotherapy is like beating the dog with a stick to get rid of his fleas! The book ends with hope, but not with much enthusiasm for a cure in the near future.

The book would have done well with a neat glossary, especially since it juggles a lot of medical terms. Perhaps future editions would surely attend to this shortfall. The volume is a bit bulky too, with 470 pages. The readers don’t glide as smoothly with the author after the first 100 pages. The remaining parts are more interesting to medical practitioners than other readers. Also, some of the trial results presented as proof of argument don’t seem to be statistically significant. The study which analysed the death rate due to lung cancer in smokers is an example. Out of 789 deaths a trial group, 36 deaths were due to lung cancer and all of them were smokers. Mukherjee then asserts, “The trial designed to bring the most rigorous statistical analysis to the cause of lung cancer barely required elementary mathematics to prove its point” (p.249). There is no disputing the fact that smoking causes lung cancer, but doctor, the mathematics involved here may not be as elementary as you think. The conclusion must depend on the ratio of smokers to the total population. If it is so high as Dr. Mukherjee himself claims in a previous page, “in some parts of the world, nearly 9 out of 10 men were smoking cigarettes” (p.241), the result proves nothing. If smokers constitute 90% of the population, it is quite probable that out of the 36 dead, all of them were smokers. We could have also argued that all of them were right-handers as if right-handedness was a cause for premature death.

A really good work. The book is highly recommended.

Rating: 3 Star