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THE EMPEROR OF ALL MALADIES: A BIOGRAPHY OF CANCER By SIDDHARTHA MUKHERJEE REVIEWED By GOKUL RAJAN "In the folklore of Science, there is often- told story of the moment of discovery: the quickening of the pulse, the spectral luminosity of ordinary facts, the over heated, standstill second when observations crystallize and fall together into patterns, like pieces of a kaleidoscope..... But there is another moment of discovery- its antithesis- that is rarely recorded: the discovery of failure. It is a moment that a scientist often encounters alone." --- Siddhartha Mukherjee, in The Emperor of All Maladies

Siddhartha Mukherjee- the biographer of Cancer, an outstanding scholar, finished his high school from St. Columbus, New Delhi, to join Stanford University where he graduated with a degree in Science, working in a Nobel Laureate, Paul Berg’s lab. He went to Oxford as a Rhodes Scholar (from India, in 1993) to do DPhil (in Immunology) which he finished in just two years, his work was on EBV (Epstein–Barr virus). He attended the Harvard Medical School to study medicine. Mukherjee is now a physician-scientist, assistant professor of medicine at Columbia University and a staff cancer physician at Columbia University Medical Center. As a physician-scientist, he is driven by compassion and curiosity. He shares an unbiased interest in science, medicine, art, literature and music. His interest in literature is reflected in his writings. A book- a project- to understand the past, present and future of an illness. Mukherjee, an excellent storyteller takes you on a journey to uncover the immense history of an illness with which we have lived for thousands of years - in about 500 pages - which itself seems like a difficult task, but is beautifully accomplished. The project took 5 long years, utilizing only the ‘interstitial’ time between his practice and research. The product - is a priceless book. The book isn’t only a story of cancer treatment, as some reviewers have put it. Mukherjee calls it a biography - “an attempt to enter the mind of this illness, to understand its personality, to demystify its behaviour.” The book grew from an attempt to record the past, present and future of our “war on cancer”. It is a book, to which one can point and tell, that this book will take you to the history, politics, literature, science and medicine of the most dreaded illness - Cancer and, probably, the earliest illness to strike humans because Life and Cancer, both come in the same package, a by-product of evolution. It is, in fact, an intellectually stimulating book, the stories are thought-provoking. Numerous stories run in parallel. Many researchers - experts and amateurs, physicians, statisticians, physicists, chemists, politicians, socialites, and most importantly - gallant patients have contributed to the “War on Cancer”. Two prominent warriors of this war, as described in the book are Farber and Lasker- the duo who pushed the war on cancer, to make it a public and political issue of utmost importance. The book doesn’t stop with the history of ‘War on Cancer’, it is something greater. Like any history, this too teaches you a lot about Science and Medicineits course and action. What palliative and preventive medicine can do to the treatment-oriented medicine, no disease in the history, take TB or smallpox, could have been eradicated with only treatment-oriented medicine. A disparity is broached between goal-driven science (like the

Manhattan project) and curiosity-driven science (like quantum physics or the quest to understand human brain and mind), and their interdependence is conveyed. Like the history of inventions and discoveries always told us, here too, anyone who tried anything unconventional to treat cancer was ridiculed by scientific community. In fact, the first two cancer “cures” - by Min Chiu Li at NCI and Frei and Freireich at NCI were not even recognized by the scientific community, and Li was fired from NCI for his path breaking work. These and many such hidden themes run throughout the book, I like to call them as the hidden-takeaways. And history, as always, repeats itself. In the 16th century, Andreas Vesalius, disappointed with the scope of Galenic anatomy, was mapping the ‘normal’ human anatomy himself, and in the 18th century, Matthew Baillie was tracing the anatomy of ‘diseased’ bodies. These events were pivotal in our understanding of human diseases. Similarly, was started the Human Genome Project in 1989, to understand the ‘normal’ human genome, and now we have scores of programs which are looking into the ‘diseased’ genomes (say, the Cancer Genome Atlas, and other such programs running around the world for different sets of population), creating a map of abnormal genomes, which is essentially what we did 3-4 centuries before, but this time only for a greater understanding of human diseases- at a different level- the molecular level. I was busy with my hectic lab work, and could find time to read this book only when shuttling between my lab and home, often in the dim lights of the connecting buses - I was reading a book of hope - a book which rejuvenated me everyday. Tracing the history of this illness, with Mukherjee, became a part of my day, everyday, for a month. But, before the book was published, none thought that this book would be a success, and declined to publish it, as no one would like read about the dreaded disease - Cancer. Now, it is a Pulitzer winner, a masterpiece of its own kind. The book was also described by the TIME magazine as one of the 100 most influential books of the last 100 years. But Mukherjee says that the true achievement of the book will be, if it eradicates the stigma associated with the disease. As he puts it in the book when referring to 1960s when the role of cancer causing viruses was hyped in the public, “If the cancer germ had infected one space most acutely, it was the imagination of the public - and, equally, the imagination of researchers.” The germ remains flourishing, indisputably. The stigma associated with the disease still persists in many societies, and embarrassingly enough, also in my own country. Someone rightly said “Siddhartha Mukherjee.... examines cancer with a cellular biologist’s precision, a historian's perspective, and a biographer’s passion.” The book's success also relies on the immense research that supports the book. The puzzle of Cancer unfolds, piece by piece, from the 500 BC Persian queen Atossa who underwent mastectomy for her breast tumor to the twentieth century drug specific chemotherapy using Herceptin. A story of how our understanding of the disease evolved from Galen’s black bile to Weinberg’s oncogenes, via Ehrlich's idea of molecular specificity. Prof. Weinberg, I recall, a pioneer in oncology, and a down-to-earth man, who was always willing to answer my endless queries. I also believe that the book had an impact on us, on many of us who read the book - some quit smoking because they were never told about its harms so lucidly, others now know how crucial it is to practice preventive medicine, many parents will now think twice before they discard their child’s umbilical cord into the hospitals sink, students of biology who often don’t appreciate epidemiological studies must have been hooked on to it by now, as I started reading more and more about the Doll and Hill study and the Framingham study, even before I finished the book. Cancer is a distorted version of ourselves, but distorted only to make itself a more perfect sibling of ourselves. “The Distorted Version of Ourselves”, fifth part of the book, is a gift to every biologist - a splendidly written story on our investigation of an illness- a story where we

frequently encounter serendipitous events. But, a greater challenge remains, greater than the illness itself, it is the social stigma associated with the disease- for no sensible reason if any. To me, as a student of Science, human nature and behaviour has always fascinated me, and when I study cell biology and cancer, though strange, it is again the nature and behaviour what fascinates me- the behaviour of both, normal and malignant cells. How a cell in the colon, precisely expresses genes to swim through the blood, reaching liver and then making itself comfortable in liver by expressing more liver-friendly genes, and more selfishly, more genes to derive more blood vessels for the tumors growth- and this disaster is nothing external- it is stitched within our genome- these genes are the very normal genes that are otherwise expressed at a different point of time, in a different class of cells. Then, it is a normal cell, gone ‘psychotic’. The last part is boldly titled as “The Fruits of Long Endeavours”, and is a glimpse into the success that we have achieved. Though, we have not won yet, we’re fighting with all-new weapons and a fantastically different strategy. When, the decrease in cancer figures is what indicates our success, it is not the only criteria. As Cancers are different diseases, we’ve to conquer it differently. Today, most patients with Chronic Myelogenous Leukemia (CML) live a near normal life- with a single pill - Gleevec. Many other cancers are also well managed using surgical, chemotherapeutic and radiation techniques - Hodgkin’s lymphoma, childhood leukemia, breast cancer, only to name a few. In the book, Mukherjee returns to some of his patients, especially Carla Reed, an acute lymphoblastic leukemia patient who later attained a complete remission - which he clarifies are not selected because they were all cured- but because they were cured by following conventional regimen. A dynamic Science has now merged with Medicine - Molecular Medicine is born, to change the way we look at these diseases. The book reminds us of our unique position in the history of medicine, and how we’re reinventing medicine. It's a must read- a masterpiece- you must have on your shelf. One of the best books I’ve ever read. We wish Siddhartha Mukherjee, a very good luck for his next, second project, and we are waiting for it!

The emperor of all maladies