The Philadelphia Chromosome: A Mutant Gene and the Quest to Cure Cancer at the Genetic Level

Almost daily, headlines announce newly discovered links between cancers and their genetic causes. Science journalist Jessica Wapner vividly relates the backstory behind those headlines, reconstructing the crucial breakthroughs, explaining the science behind them, and giving due to the dozens of researchers, doctors, and patients whose curiosity and determination restored the promise of a future to the more than 50,000 people diagnosed each year with chronic myeloid leukemia (CML). It is an astonishing tale that will provide victims of other cancers and their loved ones realistic hope that cures may yet be found in their lifetimes.The Philadelphia Chromosome charts the milestones that led to present-day cancer treatment and tells the inspiring story of the dedicated men and women who, working individually and in concert, have sought to plum the mysteries of the human genome in order to conquer those deadly and most feared diseases called cancer.

The Philadelphia Chromosome: A Mutant Gene and the Quest to Cure Cancer at the Genetic Level

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Overview

Product Details

ISBN-13:	9781622311774
Publisher:	HighBridge Company
Publication date:	05/14/2013
Edition description:	Unabridged; 9.75 hours
Pages:	585
Product dimensions:	5.10(w) x 5.90(h) x 0.90(d)

About the Author

Coming soon...

Author's Note ix

Foreword Robert A. Weinberg xi

Prelude: Down to the Bone, February 2012 1

Part 1 The Chromosome and the Disease, 1959-1990 13

1 The First Clue 15

2 Three Hundred Words 19

3 Investigating a Chicken Virus 25

4 Right Number, Wrong Place 33

5 The Surprising Source of the Chicken Cancer Gene 40

6 Consummate Instigators 49

7 Where the Kinase Hangs the Keys 53

8 A Chemical Amputation 57

9 Stripping Away the Fur and the Fat 64

10 A Funny New Protein 69

11 The First Sign of a Human Cancer Gene 75

12 Spelling Out the Translocation 81

13 "That Word Is Oncogenes" 87

Part 2 Rational Design, 1983-1998 93

14 Becoming a Doctor, and Then a Scientist 95

15 Turning a Protein into a Drug Target 104

16 A Machine with a Virus for a Motor 112

17 Plucking the Low-Hanging Fruit 116

18 A Drug in Search of a Disease 120

19 Two Endings 129

20 Getting Out of Boston 133

21 Killing Cells 138

22 Gain and Loss 147

23 "Not Over My Dead Body Will This Compound Go into Man" 156

Part 3 Human Trials, 1998-2001 173

24 The Quickest Answer 175

25 Getting to 200 Milligrams 181

26 The One Thing They Didn't Have 190

27 Buzz in the Chat Rooms 199

28 Saving Their Own Lives 202

29 A Response Rate of One Hundred Percent 210

30 Good Stressful 213

31 Putting It in Writing 221

32 A Truck load of Data 226

33 The Fathers of Victory 234

Part 4 Aftermath 241

34 A Price to Pay 243

35 Showing a Weakness 247

36 The First Five Years 253

37 The Second Generation 257

38 A Gleevec for Every Cancer 261

Epilogue: Survival Time 270

Glossary 273

References 283

Acknowledgments 291

Index 293

Photo Credits 302

About the Author 303

What People are Saying About This

From the Publisher

“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

Siddhartha Mukherfee

“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

From the B&N Reads Blog

Page 1 of

Editorial Reviews

From the first sighting of a strangely shaped chromosome to modern-day drug design, which often relies on computer modeling, cancer research has depended on translating lab results into practical treatments for patients. In her first book, science journalist Wapner expands on her reportage with a meticulous account of the half-century effort to battle chronic myeloid leukemia, a deadly cancer that only in recent years has met its match—the targeted drug called Gleevec. Narrator Heather Henderson conveys Wapner's fluid prose with a calm yet dynamic delivery. VERDICT Recommended for all listeners. This is a layperson-friendly piece of medical writing. For those who are worried about drowning in detail, no life jacket is required. ["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," read the review of the Experiment hc, LJ 5/15/13.—Ed.]—Kelly Sinclair, Temple P.L., TX

Library Journal - Audio

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). But the story of Gleevec’s progress also illuminates how a “minute chromosome”—discovered in Philadelphia in 1959—led scientists on a journey to the genetic roots of cancer and “the modern era of personalized medicine.” Gleevec’s triumph—a 2012 study conducted of patients who had taken the drug 10 years ago showed a 68% survival rate—ultimately overcame the daunting unwillingness of Big Pharma and oncologists to accept a lab-synthesized “molecularly targeted medicine.” “In eighteen years,” Wapner writes, “a vision had been wrestled into reality.” Her gracefully written history skillfully combines both the science and humanity of this fascinating search for a cure for CML, including the heartbreaks of Gleevec-pioneering M.D. Brian Druker, thwarted efforts to get the drug into trials, jealousies between scientists, the love story of a reporter and Druker, and the compelling accounts of the patients themselves, who bravely tested the drug and ultimately reclaimed their lives. 8-page photo insert. Agent: Russell Galen, Scovil Galen Ghosh Literary Agency. (May 13)

Publishers Weekly

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

From the Publisher

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

The Wall Street Journal

Among a small cluster of very good recent books on cancer.”
—The New York Times

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

The Washington Post

[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

American Scholar

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

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

The Scientist

A thriller with a dash of history.”—Science

Science

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

The Barns & 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

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

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

Nature Medicine

[The Philadelphia Chromosome] opens our eyes to a future in which remedies will kill tumors at their root.”
—Philadelphia Inquirer

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

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

Helen Lawce

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

Siddhartha Mukherjee

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

David B. Agus

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

David Quammen

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

Seth Mnookin

Freelance science writer Wapner has created a well-rounded work about the discovery of the Philadelphia chromosome, the causes of chronic myeloid leukemia (CML), and the development of the drug Gleevec to treat CML. Wapner does an excellent job of describing the many stages of basic, nonhuman, nonclinical research needed (some of which at first seemed to have no connection with the disease) that led to the knowledge necessary to treat CML. The book also illuminates the process of drug development and the tug of war between caution about side effects and the desire to cure cancer. The story also calls into question regulations that inhibit some industry/academic collaborations. VERDICT A refreshingly balanced view of the topic compared to the one-sided optimism found in Daniel Vasella and Robert Slater's Magic Cancer Bullet (2003). 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.—Margaret Henderson, Midlothian, VA

Library Journal

Science writer Wapner uses the development of a successful cure for a once-fatal form of leukemia to illustrate the application of genetic engineering to the frontiers of current medical practice. The discovery of the structure of DNA unleashed the potential to use genetically engineered pharmaceuticals in the treatment of cancer. It took longer than the succeeding 10 years for phrases like "genetic mutation" and "chromosomal abnormality" to become part of the scientific vernacular. By 1959, when the available investigative tools were still primitive by today's standards, a researcher at the University of Pennsylvania discovered an abnormality in the relative sizes of two chromosomes. Ultimately, this led to an understanding of the role of oncogenes, but first a marriage had to take place. The prevailing theory, based on the study of chicken tumors, was that since cancers were contagious, they were caused by viral infection. After virologists determined the genetic makeup of viruses, they opened a second trajectory for the research. They made the remarkable discovery that a normal, proto-oncogenetic chicken gene was temporarily assimilated into an "infecting" virus where it mutated. Normally, the proto-oncogenes were also found in healthy humans, as well as chickens and other animals. Now that the gene was identified, a similar process was discovered in the Philadelphia Chromosome. In this case, a mutated oncogene was located at the point where two specific chromosomes split and interchanged positions before their parts were rejoined. The next problem was to establish the gene's role in normal cell regulation and how to block its functioning after it had mutated. 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

The Philadelphia Chromosome: A Mutant Gene and the Quest to Cure Cancer at the Genetic Level

The Philadelphia Chromosome: A Mutant Gene and the Quest to Cure Cancer at the Genetic Level

Audio CD(Unabridged; 9.75 hours)

Audio CD(Unabridged; 9.75 hours)

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Overview

Product Details

About the Author

Table of Contents

What People are Saying About This

Customer Reviews

Related collections and offers

Overview

Product Details

About the Author

Table of Contents

What People are Saying About This

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Customer Reviews