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These articles, books, and other publications provide summaries of research, historical perspectives, and other references. Many of these works are review articles, papers that synthesize the most pertinent original research in a given field. Additional reference materials were used as sources for this book, but the following represent the most key reports.
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ACKNOWLEDGMENTS
Thanks to all of the scientists and clinicians who agreed to interviews, including Brian Druker, Naomi Rosenberg, Owen Witte, David Baltimore, Nick Lydon, Alex Matter, Daniel Vasella, Charles Sawyers, Steve Goff, Sir Philip Cohen, Ray Erickson, Herb Abelson, Michael Mauro, Peter Nowell, Janet Rowley, Jürg Zimmermann, Elisabeth Buchdunger, Helen Lawce, Renaud Capdeville, John Goldman, Peter Traxler, Moshe Talpaz, Brian Hemmings, Peter Parker, Emil Freireich, George Daley, J. Michael Bishop, Nora Heisterkamp, Kara Johnson, and Joel Crouch. Additional thanks go to Steve Goff and Helen Lawce for reading and commenting on early drafts. I thank Gary Eichner, Judy Orem, Frank Orem, Alice Hungerford, Hans Loland, Beverly Alex Owens, Kelly Mitchell, Suzan McNamara, Alexandra Hardy, and Jennifer Gangloff for sharing their stories and allowing me a glimpse into their personal lives. Thanks also to LaDonna Lopossa, Dori Mortenson, Jay Weinstein, and Virginia Garner. I also want to recognize all those who contributed to the STI Gazette and the “Appreciation Album,” both of which were source material for this book.
To all of these individuals, I hope I have shown respect in walking the hallowed ground of other people’s lives.
This book emerged through the encouragement and support of many people. At my publisher, The Experiment, those people are Matthew Lore and Nicholas Cizek. Thanks also to Russell Galen, literary agent. I’m grateful to Sarah Bowden and Elisa Williams at OHSU and Sarah Kestenbaum at Ruder Finn for their assistance, and to Norma McLemore for copyediting and Jason Rothauser for proofreading. Steve Kurlander, Paul McDaniel, Tanya McKinnon, Siena Siegel, and Joy Pincus were also all part of this book coming to life.
I thank my family for giving me space, inspiration, and comic relief.
I have done my best to tell this story accurately, referring to the published literature to check the science and the data and, as much as possible, cross-checking each person’s memory of the events described in this book. Any errors, omissions, or oversimplifications are my own and should not be misconstrued as a reflection on anyone mentioned above.
INDEX
A
Abelson, Herb
career, 57, 63, 67, 88
research, 58, 67, 76, 78, 87, 99
Abelson virus
cloning, 77
discovery, 58
gag/abl fusion gene, 83
genome, 78
Goff’s work on, 76
transformation system, 67, 68, 69, 71
Witte’s work on, 70
abl gene, 78, 82, 84
Abl kinase, 73, 74, 87, 113
abl oncogene, 78
abl probe, 82
Abl protein, 72, 73, 80, 88, 118, 126
academia-industry collaborations, 117, 130, 262
accelerated approval, 214, 215, 230
acquired resistance, 250, 251
acute lymphoblastic leukemia, 22
acute myeloid leukemia (AML), 22, 39
acute promyelocytic leukemia, 39
adenosine, 47
adenosine triphosphate. See ATP
American Society of Hematology (ASH)
phase I study results presentation (1999), 208, 210, 213
preclinical results presentation, 150
Amgen, 157
AML. See acute myeloid leukemia
anti-kinase drugs, 107, 128
antibodies, 69, 102
against phosphotyrosine, 102, 116
antifolates, 59
antigens, 61
ara-C, 193, 205
aromatase inhibitors, 107
ATP (adenosine triphosphate), 47, 54, 73
B
B-cell cancer, 61
B-cell leukemia, 76, 81
B cells, 61
b-raf gene, 268
baculovirus, 115
Bagby, Grover, 136, 137, 150
Baltimore, David
about, 67, 73, 77, 152
career, 30, 64, 65
lab, 65, 68, 69, 70, 71, 72, 75, 76, 77, 82, 83, 86, 88, 102, 127
research, 30, 64, 65, 68
banding techniques, 37, 58, 88
Barbacid, Mariano, 98
Basel (Switzerland), 110
Bayh-Dole Act, 263
bcr/abl gene, 85, 127
Bcr/Abl kinase, 89
inhibitor drug testing, 138
Bcr/Abl protein, 86, 89, 102, 118, 127
Bcr/Abl tyrosine kinase, 86, 106, 118
bcr gene, 84, 85
“bench to bedside,” 100
Beth Israel Hospital (Boston), 134
Bishop, J. Michael
about, 50
career, 43
research, 41, 46, 68, 72, 75, 77, 78, 88, 98, 99
Blanke, Charles, 247
Blasdel, Carolyn, 10, 186, 218, 270
“blast crisis,” xiii, 5, 37, 86, 176, 178, 196, 198, 204, 216, 218, 226, 249
Blueprint Medicine, 269
bone marrow transplants, 90, 161
Boveri, Theodor, 34
Boyer, Herb, 50
brain cancer, 106, 247
brand name, 231
breakpoint cluster region, 84
breast cancer, 114, 187, 235, 266
Bristol-Myers Squibb, 257, 258
Buchdunger, Elisabeth
about, 110, 141, 146, 150
career, 116, 157
research, 125, 126, 128, 148, 163
Bullitt, John, 96
C
CAMK family, 266
Canaani, Eli, 84, 118
cancer
about, 13
appearance of new mutations, 267
Druker’s interest in, 52
genetic abnormalities and, 22, 29, 34, 45, 267
kinases and, 89, 92, 106, 118
mutations and, 15, 17, 83, 252, 260, 261, 267
as tolerable chronic condition, 267
t
ranslocations and, 39
transmission, 27
triggering, 30
tyrosine and, 55, 58
and viruses, 27, 30, 58, 88
cancer research, 96, 261
cancer treatment, xi, 59, 93
antifolates, 59
bone marrow transplants, 90, 161
chemotherapy, 90
cisplatin, 109
corticosteroids, 59
cost to patient, 243, 259, 265
crizotinib, 268
dasatinib, 257, 258
delivery systems, 148
drug resistance, 248, 257, 261
erlotinib, 265
inadequacy of, 101
interferon, 105, 181, 189, 191, 205, 219, 243
isoquinolinesulfonamides, 110, 123
lapatinib, 266
Matter on, 104
Medicare coverage for, 243
nilotinib, 258
ponatinib, 260
poverty and, 264
sunitinib, 266
tamoxifen, 132, 235
targeted therapy, 109, 266, 267
See also drug development; Gleevec
Capdeville, Renaud, 213
Castagna, Monique, 106
cell theory, 16
CGP-53716 (Ciba-Geigy), 138
CGP-57148B (Ciba-Geigy)
animal testing, 152
development of, 128, 138
drug candidate testing, 138
human testing, 154
intravenous formulation, 149, 157
investigational new drug (IND) application, 154
limited market for, 142, 145, 169
marketing projections for, 169
marrow-cleaning approach, 145
method of delivery, 149, 155
oral formulation, 149
phase I clinical trial, 146, 154
presentation of preclinical results at conference, 150
publication of preclinical studies, 149
See also STI-571 (Novartis)
chat rooms, phase I patients, 199
chemotherapy, 90, 108
ara-C, 193, 205
cisplatin, 109
goal of, 180
interferon, 105, 181, 189, 191, 205, 219, 243
tamoxifen, 132, 235
See also cancer treatment
The Philadelphia Chromosome Page 31
