The Philadelphia Chromosome: A Genetic Mystery, a Lethal Cancer, and the Improbable Invention of a Lifesaving Treatment

by Jessica Wapner, Robert A. Weinberg (Foreword by)

Overview

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.

Product Details

ISBN-13:	9781615191970
Publisher:	The Experiment, LLC
Publication date:	04/08/2014
Edition description:	Reprint
Pages:	344
Sales rank:	717,880
Product dimensions:	5.40(w) x 8.10(h) x 1.10(d)

About the Author

Author of One Renegade Cell: How Cancer Begins, and The Biology of Cancer, Robert Allan Weinberg is a Daniel K. Ludwig Professor for Cancer Research at MIT and American Cancer Society Research Professor; his research is in the area of oncogenes and the genetic basis of human cancer. Weinberg is also affiliated with the Broad Institute and is a founding member of the Whitehead Institute for Biomedical Research.

Jessica Wapner is a journalist and former science editor at Newsweek whose work has appeared in The New Yorker, The New York Times, Wired, Medium, Discover, Popular Science, Self, Scientific American, New York magazine, The Atlantic, and elsewhere. Her first book, The Philadelphia Chromosome, was named a top ten nonfiction book by The Wall Street Journal. She lives in Brooklyn.

Read an Excerpt

CHAPTER 1

THE FIRST CLUE

David Hungerford could not believe what he was seeing.

He hovered over a microscope, turning the wheels this way and that to ensure the best view. A small glass slide was illuminated from below. It held a single cell that had been expanded and then stopped in the middle of reproducing, its forty-six chromosomes on full display. He checked and rechecked, and was absolutely certain: One of the chromosomes was too short.

It was 1959, the year that the genetic root of Down syndrome — an extra copy of one chromosome — had been found. The field of genetic research was almost nonexistent. The 1956 confirmation of the standard number of chromosomes housed in the human cell — forty-six, in twenty-three pairs, one set inherited from each parent — hinted at something impossible to grasp, a continent on a horizon too distant to see with the tools of the day. Even though James Watson and Francis Crick had made their famous discovery of the helical structure of DNA in 1953, the search for connections between DNA and disease had only just begun. Around the world, laboratories were just starting to toy with the kind of technology needed to explore genetic matter. Genes were units of heredity, a way for traits to be passed on from one generation to the next, including deficiencies. But how disease could possibly be linked to DNA was entirely unknown. Phrases like "genetic mutation" or "chromosomal abnormality" were not part of the vernacular yet because there was no need for such language.

And so it was that David Hungerford, a young scientist hovering over a microscope, was stunned by what he was seeing through the lenses. This was a man who knew how chromosomes should look. Camera-equipped microscopes were hot laboratory commodities in the 1950s, and Hungerford, an avid photographer, had gotten a job working with one in a Philadelphia cancer research center. He spent countless hours looking at the starfish-shaped chromosomes of the drosophila fly, training his eyes to see the fine banding patterns within. He was one of a handful of people alive at the time who could have spotted an anomaly among a blurry, inky array of chromosomes.

So it may have been inevitable that he'd ended up working with Peter Nowell, a doctor also in his early thirties doing cancer research across town at the University of Pennsylvania. In 1956, Nowell had accidentally stumbled upon a new method for seeing chromosomes inside cells. He had been studying blood cells from leukemia patients, his work following the usual approach of the day: rinsing the cells and staining them with a bluish-purple dye.

Science had come a long way in its ability to peer inside cells, the basic structural units inside every living thing, since they were first spotted by microscope in 1665. That discovery led to others, which led to the creation of cell theory, the notion that all living things are made of cells, and that new cells are made when old cells divide. But the cutting-edge techniques for seeing the inner clockwork were still rudimentary, calling for the scientist to squash a drop of cells on a covered glass slide with the thumb in order to put pressure on the cells. The squash was supposed to burst the cell, spilling out its gene-filled middle. But the approach failed as often as it succeeded, leaving behind broken cell fragments that were useless to researchers. People were frustrated with the technique, which wasted precious time and resources.

One day Nowell took a shortcut around the usual scientific procedure. "Pete was in a hurry, as young men tend to be," Alice Hungerford, David's wife, would recount years later. Instead of following a more rigorous cleaning method, Nowell washed a sample of white blood cells under some tap water. He dropped the rinsed cells onto the slide and was amazed by what he saw through the microscope. The tap water, it turned out, was hypotonic — a low-pressure solution that caused the cells to swell, like a deflated raft being blown up with too much air.

With the cells ballooned like that, Nowell could see something else equally surprising. It turned out that a bean extract he'd applied to help clot the red blood cells (making them easier to remove from a sample) had also stimulated division in the white cells. Captured in the midst of dividing, the cells were at their most expanded. Because the tap water had further expanded the size of the cell, the chromosomes had more room to spread out and were suddenly easier to see and count. No one was looking at chromosomes this way. Nowell hadn't known it was possible. Then again, he knew nothing about genes and had little interest in genetics. But he kept the slide, figuring someone out there might be interested in taking a look.

The genetics community was small then, and the number of people in the Philadelphia area interested in genetic research could be counted on one hand. Hungerford heard about Nowell's slide. The two began working together. For years, Nowell prepared slides that Hungerford would study under the scope. They perfected the hypotonic solution, still used in molecular genetics today, and figured out how to air-dry slides to help the cells spread out even more. But they saw nothing noteworthy.

Then, in 1959, three years after they'd met, there it was: an abnormally small arm of a worm-shaped chromosome inside a cell of a person with CML. With the chromosomes splayed in the squashed cell, Hungerford could clearly see that one was too small. A piece of it was missing. They looked at blood samples from six other CML patients and found the same abnormality.

Stunned, Hungerford snapped the camera shutter. He would not live to see the significance of the picture he'd just taken. In 1959, the effect that a single photograph showing a single mutant chromosome would have on the lives of countless patients and on the future of cancer treatment was entirely unsuspected.

"Until we stumbled over this Philadelphia chromosome, there was really no evidence that cancer might be due to genetic change," Nowell, now 79, said decades later. This photograph would become the lasting portrayal of a moment when everything changed for cancer and medicine as a whole. It was the as-yet unrecognized starting point for the modern era of targeting cancer at its root cause.

CHAPTER 2

THREE HUNDRED WORDS

At the time of their discovery, David Hungerford was spending about ten hours a day looking at fly chromosomes, and Peter Nowell had just returned to the University of Pennsylvania. Nowell had originally started working in the pathology lab there as a summer job in 1950. A cocky and charismatic med student, Nowell had felt certain that, given the chance, he could "solve this cancer problem" in a matter of months. But that summer he got married, and the Phillies were on their way to winning the pennant, distractions that, he said, delayed his plans to cure cancer.

But those few summer months were enough for Nowell to understand just how vast a territory he'd entered into as a cancer researcher. "I really knew very little about the specifics of things," he would say later. "In those days, it was true of pretty much everybody." He decided to take an internship for a year with a hematologist at a nearby hospital. It was there that he had his first serious education about cancers of the blood — how devastating and how complicated these diseases really were.

There were the leukemias that took over the white blood cells, with chronic versions that progressed slowly and acute versions that led to rapid destruction of the immune system. White blood cells, which fight infections, normally numbered 4,000 to 10,000 per microliter of blood. Leukemia patients typically had counts in the hundreds of thousands per microliter. The lymphomas, Nowell learned, poisoned the lymph, another infection-fighting part of the immune system concentrated primarily in bean-shaped nodes throughout the body. Lymphoma could pass from one node to another, like a fungus spreading through a forest. Multiple myeloma was a cancer of the plasma — the yellow-colored liquid that holds red blood cells, white blood cells, and platelets in suspension as they course throughout the body — filling the marrow with malignant cells, which compromise the immune system and erode bones.

These were the so-called liquid cancers, or hematologic malignancies. For cancer researchers, they were often easier to study because of their accessibility. It was much simpler to draw fluid out from a vein than to cut a patient open to excavate a solid tumor buried deep inside the body. But being able to get at the cancer hadn't led to more significant advances in treatment. When Nowell was in medical school, most types of liquid cancers were still incurable.

On rounds, he saw the victims of these harsh diseases. They brought to life the horrors of cancer more than any squashed cell ever had. A young person getting his first palpable glimpse at death, Nowell saw how shallow he'd been when he first arrived at Penn. Humbled, he realized that cancer was a beast the world had been wrestling for centuries, and against which few meaningful strides had been made.

Then, just when he was feeling a surge of dedication to the long haul of cancer research rise up in him, Nowell was drafted into the military. He was sent to San Francisco to work at the US Radiology Defense Laboratory, where he was assigned to a team studying the potential effects of radiation. The government wanted to know the possible dangers associated with the fallout from nuclear testing in the Pacific. The risks to people included diminished numbers of red and white blood cells circulating in the body in the short term and, in the long term, leukemia and other malignancies. Again, the horrors of cancer were made ever more apparent to him — this time, even more so as he witnessed the man-made devastation.

In 1956, Nowell returned to Penn, as determined as ever to solve this cancer problem.

Hungerford, on the other hand, had no desire to cure cancer. It just wasn't his way as a scientist. He had taken the more scholarly PhD route, and the driving force behind all of his work was a love of observation — to look, to record what he saw, and to share those findings with anyone else who might be interested. Compared with Nowell's passion, Hungerford's approach could seem cold and distant to their colleagues. But Hungerford was happy to record their observations for the simple reason that observations should be recorded. "He just liked to look through the microscope and see the thing," said Alice. He felt no ownership of his ideas, and he had no need for recognition. He just wanted to do the work of science; that was his role in the world. It was what made him feel alive.

Nowell and Hungerford's discovery of "the minute chromosome" was published in 1960. The report consists of three brief paragraphs in a scientific journal, without even the typical list of references that scientific papers have, set indiscriminately among a few other reports of the month. "It's three hundred words," said Emil Freireich, a leukemia doctor responsible for many major therapeutic advances, and a towering figure in the world of cancer medicine. "And it revolutionized everything."

When Nowell and Hungerford published their third scientific paper documenting the truncated chromosome in a large number of patients, with reports from groups at universities around the world confirming the phenomenon, the minute chromosome was renamed the "Philadelphia chromosome" in recognition of the city where it had been discovered.

After scientists across the world found the abnormal chromosome in their own CML cell samples, many set to work on finding other such mutants. At first, researchers thought that this chromosome was the first drop in what would soon become a waterfall of genetic mutations linked to cancer, and, they hoped, some meaningful advancement for cancer treatment. In scientific journals, the chromosome was referred to as Ph, an abbreviation that left space for other mutation discoveries to come — Ph, Ph, and so on — with researchers in other cities then following suit. But further cancer-linked mutations proved elusive. No others were found, in Philadelphia or anywhere else. Ph, as it is still often called, was found in a small percentage of samples from patients with other types of leukemia, acute lymphoblastic leukemia and acute myeloid leukemia (AML), but the link was not nearly as strong as that seen in CML. There was a brief stir over an abnormality spotted by some New Zealand researchers — the "Christchurch chromosome," people called it — but that soon turned out to be a false alarm. Whatever mutations were found appeared much more rarely than the Philadelphia chromosome did in CML. Those tenuous links hardly seemed the stuff of cancer cures.

And so enthusiasm over the Philadelphia chromosome waned, mainly because no one knew what to do with the information. "In the early years, the medical community did not care about human chromosomes," recalled Alice Hungerford, who met David when she took a job in his lab. It was like seeing a bright spot in the night sky with no knowledge of planets and solar systems. Despite the obvious connection between CML and the Philadelphia chromosome, there was very little suspicion of a causative link between genetic abnormalities and cancer. There was no technology to look any further into the mutation. In fact, it wasn't even called a mutation; it was considered a deletion. Nowell and Hungerford resisted the notion that the piece of chromosome was completely gone from the cell. They knew that such a deletion would likely be lethal. But they had no explanation for what else could have happened. A piece of genetic material had vanished. Why had it disappeared? Did the change somehow cause leukemia, or did leukemia somehow cause the change?

These were questions for another decade. Knowing the standard number of chromosomes had enabled geneticists to create a universal number language. But the view afforded by the technology at the time was so coarse that at first Nowell and Hungerford couldn't even tell which chromosome the abnormality was located on. Eventually it became clear that the deletion was from one of the two copies of chromosome 22, but that was still an incomplete description. Chromosome 22 looked an awful lot like chromosome 21 and sometimes even the Y chromosome present in males. Later, methods for staining specific chromosomes would allow for a much more discriminating study. But in 1960, these techniques were unknown. Whatever questions scientists had about the Philadelphia chromosome, there weren't any that could be answered.

Nowell and Hungerford's collaboration also reached a standstill. It was as if they had come together just to find the Philadelphia chromosome, and now, having done so, needed to move on. Nowell continued to pursue cancer research, and would ultimately spend his entire career in the same laboratory. His early success garnered him a rare lifetime government research grant. The money enabled him to pursue cancer research without the pressure to churn out publications or complete grant applications every few years, a highly limiting factor on lab research today. "I had it easy," Nowell recalled toward the end of his years at Penn, his hair as white as his lab coat. "As my wife used to say, I just assumed there was a closet with green pieces of paper in it." Nowell's grant left him free to continue research without worry about making discoveries.

Although he never again struck gold with a serendipitous discovery, Nowell contributed to important theories about how tumors evolve. He was an early adopter of the notion that tumors accrue mutations over time, a key component of modern anticancer drug development. As he put it, cancer works like a tree. A branch off the trunk is the first mutation, and every subsequent twig represents further changes to the DNA. In the end, a cell that started off just a bit different from normal accrues multiple oddities, each one enabling it to better survive in the body, and each one a potential target for a new drug. This phenomenon is at the heart of current cancer research, as scientists sift through the dozens, sometimes hundreds, of genetic abnormalities for the ones that are advancing the deadly cells.

Hungerford's life took quite a different turn. In 1971, he was diagnosed with multiple sclerosis. Not wanting to suffer the pity of his peers, Hungerford kept his disease a secret, telling only Nowell, who had become his friend and now confidant. When Hungerford's treatments and condition diminished his productivity, colleagues and grant reviewers assumed he was either lazy or untalented. His funding gradually decreased, and eventually his lab at Fox Chase Cancer Center, where he'd worked since before meeting Nowell, was shut down. Devastated, Hungerford never stepped behind the microscope again. "He did not pick up a scientific journal after that," says Alice. "It broke his heart." A longtime smoker, Hungerford died of lung cancer in 1993 at the age of 66.

(Continues…)

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Excerpted from "The Philadelphia Chromosome"
by .
Copyright © 2014 Jessica Wapner.
Excerpted by permission of The Experiment Publishing.
All rights reserved. No part of this excerpt may be reproduced or reprinted without permission in writing from the publisher.
Excerpts are provided by Dial-A-Book Inc. solely for the personal use of visitors to this web site.

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Table of Contents

Author's Note,
Foreword by Robert A. Weinberg, PhD,
Preface to the Paperback Edition,
Prelude: Down to the Bone, February 2012,
Part I: The Chromosome and the Disease, 1959–1990,
1. The First Clue,
2. Three Hundred Words,
3. Investigating a Chicken Virus,
4. Right Number, Wrong Place,
5. The Surprising Source of the Chicken Cancer Gene,
6. Consummate Instigators,
7. Where the Kinase Hangs the Keys,
8. A Chemical Amputation,
9. Stripping Away the Fur and the Fat,
10. A Funny New Protein,
11. The First Sign of a Human Cancer Gene,
12. Spelling Out the Translocation,
13. "That Word Is Oncogenes",
Part II: Rational Design, 1983–1998,
14. Becoming a Doctor, and Then a Scientist,
15. Turning a Protein into a Drug Target,
16. A Machine with a Virus for a Motor,
17. Plucking the Low-Hanging Fruit,
18. A Drug in Search of a Disease,
19. Two Endings,
20. Getting Out of Boston,
21. Killing Cells,
22. Gain and Loss,
23. "Not Over My Dead Body Will This Compound Go into Man",
Part III: Human Trials, 1998–2001,
24. The Quickest Answer,
25. Getting to 200 Milligrams,
26. The One Thing They Didn't Have,
27. Buzz in the Chat Rooms,
28. Saving Their Own Lives,
29. A Response Rate of One Hundred Percent,
30. Good Stressful,
31. Putting It in Writing,
32. A Truckload of Data,
33. The Fathers of Victory,
Part IV: Aftermath,
34. A Price to Pay,
35. Showing a Weakness,
36. The First Five Years,
37. The Second Generation,
38. A Gleevec for Every Cancer,
Epilogue: Survival Time,
PLATES,
Timeline,
Glossary,
References,
Acknowledgments,
Index,
Photo Credits,
Interview with the Author,
Reading Group Guide,
About the Author,

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

Editorial Reviews

"Among a small cluster of very good recent books on cancer."

The New York Times

"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

"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

"A thriller with a dash of history."

Science

"[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

"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

"[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

"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

"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

"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

"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."

The Wall Street Journal

"A thriller with a dash of history."

Science

"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 Lib

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

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

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

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

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

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

[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

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

Philadelphia Inquirer

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

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

The New York Times

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

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