Book Review/Science in the Media Cancer: The Whole Story

Steven A. Frank* Department of Ecology and Evolutionary Biology, University of California Irvine, Irvine, California, United States of America

For every patient and doctor, and for horrible than the disease itself. The every scientist peering at a flask of supposed miracle cures created false hope, deranged cells, this book connects the and then failed terribly. Farber was moment to the multiple voices that have determined. He was more than deter- played off each other since the first person mined. He had to find a way to treat and squeezed a painful lump and wondered cure cancer. As with so many of the great what to do. characters in cancer’s story, no was not an Reading ’s The answer. It was an obstacle to be overcome, Emperor of all Maladies: The Biography of just like the disease itself. Cancer, the full accomplishment of this Farber developed the chemicals, getting book slowly dawned on me. The story others to help. He came out of the lab, got begins with a real patient with fulminant some beds in the deepest, coldest, most and inevitable terror, and a isolated part of the hospital. At least, young doctor not sure of the course. The thought the other oncologists, don’t let protocols of recent times are applied. But anyone see what he is doing. Farber where did those treatments come from? recruited nurses and doctors, found pa- The author, working in the Dana-Farber tients whose families realized there was no Cancer Institute and tracing back the other hope, guessed at some dosages, history, comes to a hero of the past, started injecting, and ran the ward. It Sidney Farber. was far from a clinical trial in the modern In the 1940s, what did leukemia seem sense, but it was a real trial. Suffering and like to Farber and to his patients? In fact, death were the norm, but that was already Farber, originally a pathologist, did not see the baseline from which they started. patients. For the childhood that The author evokes the people, the Mukherjee S (2010) The Emperor of All fascinated Farber, the children came to the failure, the eventual halting progress. Maladies: A Biography of Cancer. : hospital, were diagnosed, and over months Once Farber’s voice has been introduced, Scribner. 592 p. ISBN 978-1439107959 died horrible deaths that devastated their (hardcover). US$30.00. the story moves off to develop other voices. doi:10.1371/journal.pbio.1001044.g001 families. There was no treatment. But But Farber continues to echo in the Farber thought the right chemical combi- background. We may find ourselves in nations could be found to control and the modern Dana-Farber hospital walking ultimately beat the disease. It was a heroic by his old office, or hear Farber’s spirit people. This is already a rich story, goal, but heroes often start as pariahs. And resonate with the personalities and the beautifully told. The author has that very perhaps, in this case, the oncologists who approaches of the great cancer surgeons rare master’s touch, evoking fully yet with shunned Farber had a point. who also tried to cure by first trying to the fewest of strokes. As readers, the The theory of was sim- destroy. How far toward death should the experienced doctor, the bench scientist, ple. Poison the patient with chemicals that treatment go? How much horror in the and the patient will all move from sketch kill cells, and hope that cancer cells die often temporary cure justifies the journey to realized story in different ways. There is faster than other cells. Hope was indeed a through hell to get there? If it takes a great detail and depth, but little to hinder. big part of the early studies. The chemical personal ego to smash through the obsta- With the patient-doctor-treatment agents were potent poisons that worked cles of professional resistance to develop counterpoint well established, the author very well, but their specificity for cancer radical chemotherapy or radical surgery, adds new voices. Treatments through the cells as opposed to normal cells was not can those giant egos learn and change as 1960s progressed, clinical trial procedures always so great. To knock the cancer back they are inevitably found to be partly right were established, broad cooperative re- took a lot of poison, which was awful for and partly wrong? search programs emerged. But the success the patient. Often, the only chance of Patients, doctors, treatments. Heroes, of treatments was confined to a few types knocking out the cancer required poison- dubious behavior, sometimes by the same of rare cancers. Overall, the total cancer ing the patient right to, and too often past, the threshold of death. If the cancer was Citation: Frank SA (2011) Cancer: The Whole Story. PLoS Biol 9(4): e1001044. doi:10.1371/journal.pbio.1001044 knocked out, the child had a brief reprieve. Soon enough the disease came roaring Published April 12, 2011 back, more aggressive and untreatable Copyright: ß 2011 Steven A. Frank. This is an open-access article distributed under the terms of the Creative than before. Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Oncologists wanted nothing to do with Farber, and did not want him ‘‘experi- Funding: The author received no specific funding for this work. menting’’ on children in their hospital. Competing Interests: The author has declared that no competing interests exist. The treatments were horrible, often more * E-mail: [email protected]

PLoS Biology | www.plosbiology.org 1 April 2011 | Volume 9 | Issue 4 | e1001044 burden changed little. Meanwhile, more of the story. We have hints about the other are minor and would have been was being learned about where the cancer factors, and just now can start to measure made by someone else had I not burden came from. A lot came from those factors such as epigenetic changes in stumbled on them first. They al- cigarettes. We get the story of the DNA markings and histones, signaling ready appear in textbooks without epidemiological research, with new heroes. changes between different cell types, and mention of my name. I am no Resistance always comes from some- so on. The author brings us all the way to Galileo, Newton, Darwin, Einstein where. This time, it’s the tobacco industry. this point, keeping Farber and other early or Watson and Crick. But I have You know the story in broad outline. The players alive through the narrative. had fun and have been rewarded details resonate with what was being This book is about giving the full sense beyond my deserts. So be it [1]. learned about the causes of cancer, with of time and pace and people. The early detection through mammograms narrative evokes detail rather than in- and the Pap smear, and with the com- structs. A reader expert in any area will see Nonetheless, a narrative following from plexities and controversies over the effica- what is left out, what is made to sound one great person to the next is often a cy of screening. Competing interests arise simple when the reality is complex. But the good way to tell the whole story: and economics plays a role. There is whole story also has a reality, and there increasing activism of the public in have been so very few authors who can tell More attention to the History of shaping research and health-related poli- us the whole story of major areas of Science is needed, as much by cies. medicine or science. scientists as by historians, and espe- Until the 1970s, so little was understood To tell the whole story, the author often cially by biologists, and this should about cancer and about how treatments focuses on individuals as heroes. The mean a deliberate attempt to under- worked, that it was all a black box. device works beautifully. Somehow, with stand the thoughts of the great Presented with a disease, one poisoned or a cast of Tolstoyian proportions, one can masters of the past, to see in what cut deeply and hoped the patient survived keep track of the individuals, and continue and the cancer died. By the 1970s, we to hear their voices even as they come and circumstances or intellectual milieu learned to measure better and run proper go. I could not imagine another way to their ideas were formed, where they trials, to cut a bit more or a bit less, to use accomplish telling such a broad story, took the wrong turning or stopped different combinations of poisons. It was because we remember well-drawn charac- short on the right track. A sense of all empirical, in that little was really known ters long after we have forgotten about the continuity and the progressive and about how different cancers differ and why some particular technical achievement in a cumulative character of an advanc- individuals respond differently to the same field far from our own. Yet, from the ing science is the best prophylactic I treatments. And why, for many cancers, perspective of understanding the history of can suggest against the manic-de- did death soon occur at nearly the same each era in a deeper and more nuanced pressive alternations of the cult of rate as before treatments existed? way, it is probably good to keep a certain vogue and boost, which threatens to Then we found some of the genes that skepticism in mind. smother the scientific efforts, gigan- mutated in cancers. We learned the In the subjects that I know well in tic as they are, of at least one great biochemical actions of different potential , I think of the false nation [2]. treatments. Could we learn to match the tendency to exaggerate the role of a few specific changes in certain tumors to individuals in ways that distort both the Modern science naturally focuses itself particular drugs designed to treat the actual contributions of individuals and the almost entirely in the present and near specific malfunctions? Briefly, the answer actual way in which scientific understand- future. But good treatment, research, and is that we did in a few cases, we are still ing was achieved. The Nobel Prize winner policy require a sense of the historical learning, and many people think great Christian de Duve, when asked how he continuity and the progressive and cumu- progress is ahead. wanted to be remembered, answered: By this point in the story, you are well lative character of advancing science—the versed in the pace of history. At any time, whole story. To learn the whole story of always slow progress up to that point, new I have no such ambition. In the cancer, read Siddhartha Mukherjee’s mas- promise imagined ahead. But, as the history of science, my contributions terful book. author develops the story of recent re- search, you also feel the accelerating pace About the Author of change on top of that slow march through time. It was only 15 years ago that Steven A. Frank is Professor of Evolutionary Biology at the University of California, we first began to get any real genetic Irvine. He develops mathematical and computational models to study problems understanding, and those first clues were in evolutionary genetics, infectious disease, and cancer. Professor Frank has scattered and unclear. It was only a couple published three books: Foundations of Social Evolution (1998), Immunology and of years ago that we began to measure the Evolution of Infectious Disease (2002), and Dynamics of Cancer: Incidence, actual genetic changes in tumors. And we Inheritance, and Evolution (2007). Further information about Professor Frank’s know that genetic changes are only a part research can be found on his Web site at http://stevefrank.org.

References 1. de Duve C (2010) The joy of discovery. Nature 2. Fisher RA (1959) Natural selection from the 467: S5. doi:10.1038/467S5a. genetical standpoint. Aust J Sci 22: 16–17.

PLoS Biology | www.plosbiology.org 2 April 2011 | Volume 9 | Issue 4 | e1001044