31 December 2010

The Emperor of All Maladies

Because I'm a research assistant in hospital epidemiology, people usually assume my Master's degree is in something like health policy/administration or infectious diseases epidemiology.  It is neither (although my scores in ID epidemiology and hospital epidemiology got me my job).  My Master's is in epidemiology and I wrote my thesis in cancer epidemiology; specifically, descriptive and analytic epidemiology of intraocular melanoma among Iowa residents using the SEER Cancer data from 1973- 2000.  I didn't really choose that topic - it fell into my lap, more or less, as a thesis-ready project - but the history and epidemiology of cancer in general is fascinating so when I spied an advance copy of Siddhartha Mukherjee's new book, The Emperor of All Maladies, on the breakroom table at the store I absolutely had to read it.

Mukherjee is an oncologist and researcher at Columbia University and teaches at the medical school.  He stands on the front line, straddling the line between clinician (treating the patient) and researcher (finding new treatments) but he started writing The Emperor of All Maladies while in his fellowship at the Dana-Farber Cancer Institute in Boston.  Several of his patients make appearances in the book, most notably Carla, a new leukemic whose story begins and ends Mukherjee's history of cancer treatment.

Leukemia is the cancer that provided the puzzle that spurred pediatric pathologist Sidney Farber to start his cancer research in the 1940s.  Leukemia was first described - as we would recognize it today - by physician John Bennett in the mid-nineteenth century.  Prior to the advent of germ theory, cell theory, and an understanding of hematopoesis (the process by which blood cells are made and matured), Bennett concluded that a young male patient had died of a "suppuration of blood" - the patient's blood had spontaneously turned to pus without any known cause (p 13).  Today, we recognize that as the final stage of leukemia where the deranged overgrowth of immature white blood cells has completely squeezed out all the red blood cells from the patient's blood and bone marrow.  Soon other cases were described.  As advances in microscopy and pathology came along, physicians began to classify solid tumors (i.e. breast, colon, lung, etc.) and hematologic tumors (i.e. leukemia).  Mukherjee notes, by 1902 a new theory of cancer had emerged which focused on the hallmark of a cancer cell: uncontrolled cell growth (pathologic hyperplasia).  Cancers could now be classified according to the type of cell grown out of control, including cancers of the blood.

But it brought physicians no closer to creating a medical treatment for cancer.  Solid tumors near the surface of the body, like those of the breast or skin, could be removed by a surgeon, possibly effecting a "cure."  Radical surgery and even more-radical surgery pioneered by William Stewart Halsted in turn-of-the-century Baltimore theorized that the more tissue or "tumor" removed during an operation, the more likely the patient is to have long-term survival.  At one point, a very radical mastectomy included not only removal of the affected breast (breasts) but the pectoralis major and minor muscles of the chest, the lymph nodes under the armpit, above the collarbone, and under the sternum, and possibly a rib or two.  Women were left disfigured and potentially disabled (without the chest muscles it is difficult to use the arms normally and the lack of lymph nodes causes severe swelling).  The discovery of radiation led to the use of radiation therapy in conjuction with radical surgery (in some cases).  But there was still little to no hope for patients with non-solid cancers or metastatic tumors (new tumors that have invaded the body at a site distant from the original tumor) that could not be cut out of the body by the scalpel.

Which brings the reader back to Farber.  Childhood leukemia was a death sentence; children came to his hospital to die of leukemia, not be treated for it.  Pediatricians felt no need to push for treatment so Faber gathered up all the available research and information about the function of normal blood cells and started applying that knowledge to childhood leukemias.  His first treatment trial using folate was a disaster because no one knew, at that time, how cells actually grow and divide.  Farber's second trial using aminopterin, an anti-folate, had good initial responses but, sadly, the children relapsed within months and died.  More trials and new and different chemicals would come; Farber had started picking at the Gordian knot that was cancer and within a few decades the discoveries would come faster and faster.

This is the real meat of the book: the development of cancer research and cancer treatment, i.e. chemotherapy.  The current model for drug development - the multi-phase, randomly-assigned, placebo-controlled clinical trial - was never used initially to develop cancer treatment.  One therapy after another was tried on terminally ill patients to see if a remission could be elicited.  Only after some success were randomized trials initiated to measure response and relapse rates and it is only in the last thirty or forty years that the greatest strides in achieving and maintaining remission have been made.  Mukherjee follows the medical breakthroughs right into the twenty-first century with the advent of inhibitors like Gleevec and ruminates on the future of cancer treatment.

The Emperor of All Maladies is an extremely well-written and engaging book.  Mukherjee doesn't dumb-down the science to the point of boringness but neither does he make it so full of medical jargon and regurgitated research results that it becomes unreadable.  This is very much a book for the everyman, for the general reading public because every person on this planet will, in his or her lifetime, either be personally diagnosed with cancer or have a family member or close friend diagnosed with cancer.  It provides so much needed information about the history of this disease.  Even medical professionals will enjoy The Emperor of All Maladies and it is a book that medical professionals need to read; Mukherjee treats his patients and subject with respect and compassion.  Even with my background, well-versed in cancer epidemiology and well-read in medical and scientific history, I found new bits and pieces of cancer history, and reminders of how quickly researchers can get out-of-hand (although I did find the third or fourth definition of "metastasis" too much repetition).

The Emperor of All Maladies is a Barnes and Noble Discover Great New Writers Holiday 2010 selection.  I really do urge everyone to visit their favorite bookstore and read this book.

Dear FTC: I read the advance copy received in my store from the publisher.

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