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The Philadelphia Chromosome: A Genetic Mystery, a Lethal Cancer, and the Improbable Invention of a Lifesaving Treatment, by Jessica Wapner
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Philadelphia, 1959: A scientist scrutinizing a single human cell under a microscope detects a missing piece of DNA. That scientist, David Hungerford, had no way of knowing that he had stumbled upon the starting point of modern cancer research— the Philadelphia chromosome. It would take doctors and researchers around the world more than three decades to unravel the implications of this landmark discovery. In 1990, the Philadelphia chromosome was recognized as the sole cause of a deadly blood cancer, chronic myeloid leukemia, or CML. Cancer research would never be the same.
Science journalist Jessica Wapner reconstructs more than forty years of crucial breakthroughs, clearly explains the science behind them, and pays tribute—with extensive original reporting, including more than thirty-five interviews—to the dozens of researchers, doctors, and patients with a direct role in this inspirational story. Their curiosity and determination would ultimately lead to a lifesaving treatment unlike anything before it.
The Philadelphia Chromosome chronicles the remarkable change of fortune for the more than 70,000 people worldwide who are diagnosed with CML each year. It is a celebration of a rare triumph in the battle against cancer and a blueprint for future research, as doctors and scientists race to uncover and treat the genetic roots of a wide range of cancers.
- Sales Rank: #299993 in eBooks
- Published on: 2014-04-29
- Released on: 2014-04-29
- Format: Kindle eBook
From Booklist
Chronic myelogenous leukemia (CML) is an uncommon but fatal cancer. More than 95 percent of patients afflicted with this malignancy have a chromosomal abnormality known as the Philadelphia chromosome. This genetic mutation is characterized by a swap of genetic matter between two different chromosomes so that a single chromosome (number 22) has a piece missing. The mutated chromosome codes for an enzyme—tyrosine kinase—that is hyperactive and ramps up production of white blood cells that leads to leukemia. A chemical compound was identified that selectively targets the kinase protein. Gleevec was FDA approved in 2001, and the results have been quite impressive. It outperformed the existing first-line treatment for CML. It is safer than a bone marrow transplant. Gleevec is unique among cancer drugs because it is taken orally (instead of administered intravenously) at home (instead of the hospital or clinic) with very manageable side effects. Science writer Wapner has pieced together a detailed account of a spectacular scientific success story and a turning point in the treatment of cancer. --Tony Miksanek
Review
One of The Wall Street Journal's 10 Best Nonfiction Books of 2013:
“There were numerous strong books about cancer in 2013, but this account of the decades of work to find a drug to fight chronic myelogenous leukemia was the strongest. Jessica Wapner translates the complexities of medical science for the general reader and demonstrates the necessity of collaboration between two traditional enemies, academia and Big Pharma.”
“Among a small cluster of very good recent books on cancer.”
—The New York Times
“This reporting takes in a huge swath of science and research, a landscape that changes dramatically over the course of her story. Wapner’s achievement is to help the reader understand why each development is huge in its time and place—starting with Hungerford peering through his camera at the chromosomes and following scientists through the laboratory stories, through drug development and animal testing, to the triumphant patient treatment when the drug becomes almost routine—a scientific miracle absorbed into the daily lives of a group of patients no longer united by a fatal diagnosis.”
—The Washington Post
“In [The Philadelphia Chromosome], Jessica Wapner chronicles the ensuing decades of laborious scientific inquiry and industrial ingenuity that led to the discovery of Gleevec, the first drug designed to attack cancer at the genetic level. Its success in beating CML into remission and making the errant chromosome disappear has helped to revolutionize cancer research, unleashing a hunt for the genetic basis of other cancers and opening the door to comparable targeted treatments.”
—The Wall Street Journal
“[A] riveting suspense story . . . Ten years ago, CML was a death sentence. Today, with Gleevec, most of its sufferers lead full and normal lives. Wapner tells the complex story of how this came to be with clarity, eloquence, and balanced insight.”
—American Scholar
“An excellent book for those who want to learn more about how medical discoveries are made and those interested in recent medical history, as well as those whose lives are affected by CML.”
—Library Journal
“A crucial link between genetics and cancer emerged in a US lab in 1959, as researcher David Hungerford peered down a microscope at an abnormally small chromosome. In 1990, this ‘Philadelphia chromosome’ was found to cause the swiftly fatal chronic myeloid leukaemia. As science writer Jessica Wapner reveals in this taut, elegant study, a cascade of breakthroughs then led to success with targeted drug Gleevec, a tyrosine kinase inhibitor—and hopes for the cancer-busting potential of rational drug design in general.”
—Nature
“[T]he way Wapner repeatedly adds up preceding steps to build to the scientific breakthrough is masterful, making for compulsive, surprisingly emotional reading."
—The Scientist
“A thriller with a dash of history.”—Science
“In this meticulously detailed chronicle, science writer Wapner recaps the remarkable development of Gleevec, a cutting-edge drug capable of beating the typically fatal cancer of white blood cells known as chronic myeloid leukemia (CML). . . .Her gracefully written history skillfully combines both the science and humanity of this fascinating search for a cure for CML.”
—Publishers Weekly
“Wapner weaves together the basic and applied science with the stories of the dedicated researchers, the broader supporting superstructure of modern medicine and the process of bringing pharmaceuticals to market. . . . An absorbing, complex medical detective story.”
—Kirkus Reviews
“Expounding the well-known link between genetics and cancer, this scientific history recounts the initial discovery of a gene mutation that eventually led to enormous breakthroughs in the fight against leukemia.”
—The Barnes & Noble Review
“Jessica Wapner reveals how the discovery of a single mutated chromosome led to a trailblazing treatment for leukemia and a variety of other cancers.”
—Shelf Awareness
“Splendidly written in the tradition of the legendary medical book, Microbe Hunters, this book proves that medical science is as cool as those forensic shows like CSI.”
—Philadelphia Weekly
“I would enthusiastically recommend [this book] to the lay public, people living with cancer and cancer researchers. . . .[T]he story of the Philadelphia chromosome—the scientific creativity and the dedication it celebrates and the medical scientific triumph it represents—is one that deserves to be cherished for eternity.”
—Nature Medicine
“[The Philadelphia Chromosome] opens our eyes to a future in which remedies will kill tumors at their root.”
—Philadelphia Inquirer
“[C]hronicles the decades-long quest to develop a targeted, or ‘rational,’ treatment that would attack cancer on the genetic level.”
—New York Post
“I enjoyed the book immensely for its enthusiasm, compassion, and depth, while remaining accessible to those not versed in science. It should become a classic.”
—Helen Lawce, Journal of the Association of Genetic Technologists
“The story of the Philadelphia chromosome is truly the story of modern cancer biology—from the very earliest description of a chromosomal abnormality in cancer cells to the development of a targeted medicine against a formerly lethal type of leukemia. Jessica Wapner stitches the whole story together with tenacity, diligence (and humor). This is a wonderful, readable, and highly informative book.”
—Siddhartha Mukherjee, Pulitzer Prize–winning author of The Emperor of All Maladies
“Jessica Wapner shows us in The Philadelphia Chromosome how the past and the future combine to dramatically change the course of a disease. This beautifully written book is a blueprint for broader healthcare change. A pivotal book.”
—David B. Agus, MD, Professor of Medicine and Engineering, University of Southern California, and author of The End of Illness
“Jessica Wapner has done two kinds of hard work gracefully: the hard work of understanding cancer genetics and the hard work of rendering that subject into human narrative, lucid explanation, and metaphor. The Philadelphia Chromosome is not just an urgently useful book. It's also an elegant one, put together like a Swiss watch.”
—David Quammen, author of Spillover: Animal Infections and the Next Human Pandemic
“The Philadelphia Chromosome clearly explains how a half-century’s worth of research transformed a viciously lethal form of cancer into a chronic, treatable condition. Jessica Wapner’s meticulously researched book is both a real-life medical thriller and an engaging narrative about the history of modern cancer research.”
—Seth Mnookin, author of The Panic Virus: The True Story Behind the Vaccine-Autism Controversy
Review
“The story of the Philadelphia chromosome is truly the story of modern cancer biology. . . . Jessica Wapner stitches the whole story together with tenacity, diligence (and humor). This is a wonderful, readable, and highly informative book.”
—Siddhartha Mukherjee, Pulitzer Prize-winning author of The Emperor of all Maladies
Most helpful customer reviews
44 of 47 people found the following review helpful.
Renewed Appreciation
By Mary Crocco
Reading the Philadelphia Chromosome transformed me into a mini scientist majoring in CML, Chronic Myelogenous Leukemia. I was diagnosed with CML in November of 2003, which required keeping up-to-date on news relating to CML. When I heard about the Philadelphia Chromosome by Jessica Wapner, I was anxious to add it to my shelf of resources.
Reading the book with pencil in hand to highlight new facts as well as valuable previous knowledge, I found myself marking information on every page.
When I was diagnosed my oncologist informed me that if there was ever a good time to get CML, it was now. At that precise moment, I had no idea what he was talking about. He may have elaborated, but in that moment of shock, I didn't hear much. Wapner's book has renewed my appreciation of that conversation every time I swallow my oral chemotherapy pill, Gleevec.
I have an entire file cabinet filled with lab results since 2003. My oncologist reviews the findings with me twice a year, but after reading the Philadelphia Chromosome, my understanding of the labs has improved. I have registered for a couple of CML conferences and am confident I will easily grasp new information presented after reading this book.
Years ago I started writing a book about living with CML. I found it too depressing to continue, however, not abandoning the therapeutic effect; I turned it into a blog, which I update once a month. marycrocco.wordpress.com Being helpful to a few readers who have stopped by makes it worthwhile.
Wapner shared a story of a patient who cherished her Gleevec and defended it with her life. I do the same thing, always insisting to sign for it and checking the delivery time is set for the morning. I don't want my miracle pill losing its potency in the heat of a UPS truck.
Thank you, Jessica Wapner, for taking the time to write this incredible book, the Philadelphia Chromosome. I appreciate the effort required in your research to share with others who suffer with CML, or readers who have an interest in cancer treatments.
Bringing to life the names of medical doctors and institutions involved in the creation of Gleevec was important. I owe my life to Dr. Druker, and others, who dedicated a large portion of their lives creating a targeted medicine to fight chromosome abnormality in cancer cells.
17 of 19 people found the following review helpful.
A Good Lesson in How We Get Cancer and How We Can Cure It
By R. Schultz
This book is divided into roughly three parts. The first part consists of an account of how scientists tracked a certain kind of leukemia down to its genetic origins. Some of the explanation here can be a little difficult. But don't be put off. While this section doesn't necessarily make for light bedtime reading - it is accessible. Wapner presents the material in short, easily digestible chapters. She frequently reviews what's been covered so far, and she is a master of writing clear, logical sentences that include analogies from everyday life. So you will readily enough be able to understand this section if you just turn off the TV and concentrate for short stretches.
Your diligence will be rewarded. At the end of this section, you'll have a clear understanding of how this type of cancer, and of how cancers in general, can arise in the very core of our cells. You'll also understand how a drug can be tailored to specifically stymie the action of the aberrant chromosomes.
The second section deals with how Brian Druker and others ushered such a drug through the necessary test phases. Reading about this often frustrating process, you'll learn how tests must progress from animal to human subjects in order to eventually try for FDA approval. The pill that was eventually formulated proved to be so much more successful at fighting back the cancer than previous drugs or procedures, it was fast-tracked for FDA approval. Here the reading gets easier, although perhaps not quite as interesting.
Finally, Wapner recounts how the drug was named Gleevec and was marketed. She also tells how this pioneering drug has opened the door to what's become a flood of other drugs targeted at blocking the chemical chain of events that arise from a mutated gene.
There's a center section of glossy photos, showing some of the people responsible for getting this drug to the public. A few of the plates also illustrate the way in which Gleevec was able to attach to and block the wildly proliferating process initiated by the mutation. It might have been more helpful if these illustrations had been rendered as ink drawings and reproduced right on the pages where Wapner's explanations of the chemical process first appear.
However, that would have been a minor clarifying point. On the whole, this book can serve as a crash course in oncology. Its lucid explanations will enable you to be a more knowledgeable partner with your Doctors should you find yourself with any cancer diagnosis. Even if you never develop any form of that condition, this book provides fascinating insights into how our bodies work.
The book includes a glossary of biological terms.
14 of 16 people found the following review helpful.
A brilliantly written book about the genetic basis of cancer
By Darryl R. Morris
n 1959 two Philadelphia researchers, David Hungerford, a scientist at the Fox Chase Cancer Center, and Peter Newell, a physician studying cancer at the University of Pennsylvania School of Medicine, made a momentous discovery that revolutionized the understanding of cancer. Hungerford, who specialized in studying and photographing chromosomes from a variety of species, looked at a slide of the cancerous cells from a patient with chronic myelogenous leukemia (CML), using a technique of halting chromosomes during division that was designed by Newell. To his great surprise, Hungerford noticed that one of the chromosomes was significantly shorter than it should have been. He took a photograph of the shortened chromosome and showed it to Newell, who subsequently prepared slides of cancerous cells from several other people with CML. Each of these patients had the same abnormal chromosome. The two published their findings in a three paragraph article in Science the following year. The study was largely ignored, as the study of genetics was in its infancy, and essentially no one suspected that cancer could be caused by chromosomal abnormalities.
Over a decade later Janet Rowley, a geneticist at the University of Chicago, studied these same cells from CML patients, using staining and visualization techniques that weren't available to Hungerford and Newell. She found the same shortened chromosome, which was by then determined to be chromosome 22, but she also found that chromosome 9 was also abnormal, being longer than it should have been. Through meticulous study of these chromosomes she correctly determined that a portion of chromosome 22 had migrated to chromosome 9, while a similar portion of chromosome 9 appeared on chromosome 22, in a process that is known as chromosomal translocation:
This translocation led to the creation of a fusion gene, made up of a portion of the abl gene of chromosome 9 and the bcr gene of chromosome 22. The bcr-abl gene, known as an oncogene, led to the production of a protein that allowed the affected cell to rapidly multiply without the normal controls exhibited by other cell types. Similar to the famous Trouble with Tribbles episode of Star Trek, the cancerous cells, which are derived from immature white blood cells, overtake the bone marrow, leading to decreased production of the normal bone marrow cells: red blood cells, normal white blood cells and platelets. Initially this causes anemia, leukopenia and thrombocytopenia, or decreased red blood cells, white blood cells and platelets in the circulatory system, respectively. As the cancerous cells continue to multiply they escape from the bone marrow and make their way into the bloodstream in large numbers, which causes profound leukocytosis, or an excessive number of white blood cells in the circulatory system. Leukemia is often diagnosed at this stage, when the blood is filled with abnormally large white blood cells.
Without any treatment to block the uncontrolled multiplication of these leukemic cells they migrate to other organs, which leads to organ dysfunction and ultimately death.
In "The Philadelphia Chromosome", Jessica Wapner brilliantly describes the painstaking research by scientists and clinicians to elucidate the mechanisms on a genetic and molecular level that lead to cancer, including the study of cancer causing viruses such as Rous sarcoma virus and Moloney virus, and the discovery of tyrosine kinase and other protein kinases, which are essential to normal function and growth in healthy cells but can cause unregulated division in cancerous cells. The bcr-abl in CML cells was discovered to code for an abnormal tyrosine kinase, and a collaboration between academia and the pharmaceutical industry led to the eventual development of the first tyrosine kinase inhibitor, imatinib mesylate, which is also known as Gleevec in the US and Glivec in most of the rest of the world. The use of this and subsequent tyrosine kinase inhibitors has allowed people with CML to live near normal lives by taking one pill a day, with minimal side effects; until the 1980s CML was a universally fatal disease. Other kinase inhibitors and similar compounds are under development, which have not yet been as successful in treating other malignancies but hold promise that cancer can be successfully controlled, if not cured, in our lifetimes.
"The Philadelphia Chromosome" is a carefully researched and very well written book, given the complexity of the techniques used in molecular biology and genetics, which also reads like a suspense novel as Wapner describes the hurdles that the discoverers of the first tyrosine kinase inhibitor faced in getting Novartis, its manufacturer, to approve the drug for clinical trials and make it available to the general public. It is a very important and timely book, which I would recommend to all readers, although it may prove to be a bit of a challenge for those readers without a basic science background. It is nearly as good as Siddharta Mukherjee's Pulitzer Prize winning book "The Emperor of All Maladies: The Biography of Cancer", and it would be a perfect next step for those wishing to learn more detail about cancer research after reading that book.
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