The Emperor of All Maladies

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The Emperor of All Maladies Page 72

by Siddhartha Mukherjee


  mustard gas, see nitrogen mustard

  mutagens, mutagenesis, 278, 303, 347, 348, 362, 364, 406, 456

  mutation, genetic, 377

  in bacteria, 277–78

  Cancer Genome Atlas and, 450–54

  causes of, see mutagens, mutagenesis

  driver (active), 453

  frequency of, 451–52

  in fruit flies, 347

  functional vs. structural view of, 455

  as governing all aspects of cancer, 387–88, 462

  as mechanism of carcinogenesis, 6, 39, 176, 278, 357, 362, 370, 380–83, 384–88, 390–92, 403, 406, 449–50, 462, 464–65

  passenger (passive), 452–53

  see also oncogenes

  myc (c-myc) gene, 382–83, 384, 391, 410, 412, 453–54, 458

  mycobacteria, 84, 131

  myelodysplasia, 306, 309, 312

  myeloid cells, 16–17

  Myriad Genetics, 381

  Nathan, David, 140

  National Alliance of Breast Cancer Organizations (NABCO), 327

  National Breast Cancer Coalition (NBCC), 426, 429

  National Cancer Act (1971), 188, 189

  National Cancer Institute (NCI), 15, 114, 130, 158, 159, 166, 177, 188, 228, 231, 318, 325, 330, 339, 374, 393, 443

  chemotherapy protocols of, 132–42, 143–50, 164–66, 206–8, 219–20, 232, 310, 317

  Clinical Center of, 128–29, 139, 145, 162, 165, 260

  creation of, 25–26

  Institutional Board of, 137

  mammography project (BCDDP) of, 296–98, 302

  Pap smear trial of, 289–90

  preventative strategies neglected by, 233–34

  Special Virus Cancer Program of, 175–76, 280–81, 356, 357

  National Cancer Institute Act (1937), 25

  National Health Service, British, 294

  National Institutes of Health (NIH), 25n, 121, 187, 188, 202–3, 260, 319

  National Library of Medicine, 261

  National Program for the Conquest of Cancer, 184

  National Science Foundation (NSF), 121

  National Surgical Adjuvant Breast and Bowel Project (NSABP), 200–201

  National Tuberculosis Association, 259

  natural selection, 248

  Nature, 354, 379

  Nature Medicine, 435

  nausea, from chemotherapy, 165, 205–6, 209, 226, 305

  Nazis, 290

  Neely, Matthew, 25, 173

  negative statistical claims, 197–98

  Nelson, Marti, 424–25, 429

  “funeral procession” for, 425–26

  neoplasia, 16, 42, 385

  neu, 410–11, 412, 413, 420

  neuroblastomas, 410, 413

  New England Journal of Medicine, 35–36, 161, 229, 330, 385

  Newton, Isaac, 370

  New York, HIP in, 294–96, 297

  New York, N.Y., AIDS in, 316, 318

  New York Amsterdam News, 286

  New York Times, 24, 26–27, 105, 117, 119–20, 180–81, 183, 319, 327, 455

  Neyman, Jerzy, 197–98

  nicotine:

  addictive properties of, 270–71

  see also cigarettes; smoking; tobacco; tobacco industry

  Nisbet, Robert, 193

  nitrogen mustard, 207, 220, 257

  bone marrow affected by, 88, 90

  DNA damaged by, 163, 406

  hyperplasia as halted by, 163, 406

  as mustard gas, 87–88, 89–90, 162–63

  nitrosoguanidine derivatives, 278

  Nixon, Richard M., 180–81, 183, 184, 187–88

  Nobel Prize, 28, 87, 91, 176, 348, 363

  Norris Center, 323

  Norton, Larry, 327, 426

  Novartis, 436, 439

  Nowell, Peter, 365

  NSABP-04 trial, 200–201, 203, 220

  Nuland, Sherwin, 38

  Ochsner, Alton, 256–57

  Oedipus the King (Sophocles), 321

  Office of Scientific Research and Development (OSRD), 90, 119

  Oliver Twist (Dickens), 239

  oncogenes, 363, 366, 370–71, 380, 384, 402, 409–11, 412, 415, 431, 439, 443, 450, 453, 454, 462, 466

  amplification of, 416

  pathological hyperplasia induced by, 357–59, 372, 431

  proto-, see proto-oncogenes

  see also specific genes

  oncology, oncologists, 304, 433

  AIDS and, 316–17

  death and, 4, 306–8, 337–38

  fellowships in, 2–5, 168

  origin of term, 47

  overconfidence of, 223, 226, 231–32, 234, 308, 310

  palliative care and, 224–26, 307

  patients’ relationships with, 199, 202, 209, 306–8, 449

  radiation, see radiation therapy

  OncoMouse, 382–83, 384

  onkos, 47

  etymology of, 466–67

  “On Some Morbid Appearances of the Absorbent Glands and Spleen” (Hodgkin), 157

  opiates, 226

  Oregon Health and Science University (OHSU), 434

  Orman, Ben, 151–53, 155, 399–400

  Osler, William, 45

  osteosarcomas (bone tumors), 43

  ovarian cancer, 59, 162, 346, 381, 450, 451, 457

  ovaries, removal of, 214, 215

  Pacific yew tree, 206

  Pack, George, 70–71

  Padhy, Lakshmi Charon, 410–11

  Page, Irvine, 187

  paleopathology, 42

  palliative care, 223–26, 231, 307

  drug trials for, 226

  pancreas, 154, 414

  pancreatic cancer, 154, 158, 450, 451, 465

  Panel of Consultants, 184, 188

  Panzer, Fred, 270

  Papanicolaou, George, 286–90, 291, 384–85, 386, 401

  Papanicolaou, Maria, 287

  papillomavirus, 174, 349n, 381n

  Pap smears, 228, 286, 287–90, 296, 303, 331, 381, 385, 401

  Paré, Ambroise, 49

  Paris, University of, 51

  Park, Roswell, 24, 45

  Parliament cigarettes, 269

  Pasteur, Louis, 57

  pathology, pathologists, 11–12, 14

  Hodgkin’s approach to, 156–57

  Patterson, James, 183

  PCP (Pneumocystis carinii), 165, 315–16

  Pearson, Egon, 197–98

  pectoralis major, 64–65

  pectoralis minor, 64

  pellagra, 110

  penicillin, 21–22, 122, 129, 465–66

  Penicillium, 122

  Pepper, Claude, 26n

  peptic ulcers, 281–84

  Perkin, William, 81–82, 83

  pernicious anemia, 27–28, 31

  Peru, 42–43

  pesticides, 456–57

  Peters, Vera, 159–60

  Peters, William, 311–15, 319–20, 321, 325, 326, 329

  Peto, Richard, 241, 249, 273–74, 462

  pharmaceutical industry, 426

  see also specific companies

  Philadelphia chromosome, 365, 430–31

  Philip Morris, 251, 269–71, 273

  phlegm, 48

  phosphorylation, 358–59, 361, 380, 418, 431–32

  Piccolo, Brian, 181

  Pim, Isabella, 58

  Pinkel, Donald, 123, 167–68, 170, 178

  pitchblende, 74

  pituitary cells, 414

  placebos, in randomized trials, 131–32, 319

  placenta, 135, 219

  platelets, 18

  Plato, 370

  Pneumocystis carinii (PCP), 165, 315–16

  pneumonectomy, 242

  pneumonia, 45

  PCP, 165, 315–16

  Poet Physicians, 60

  polio, 22, 229, 342, 466

  national campaign against, 93–94, 175

  Popper, Karl, 370

  population, U.S., aging of, 230

  Postmortem Examination, The (Farber), 19

  Pott, Percival
l, 173, 237–39, 241, 276, 447

  precancer, 286, 306, 455

  Auerbach’s research on, 258–59, 284, 289

  prednisone, 127, 140, 143, 149

  see also VAMP regimen

  Premarin, 213

  preventive medicine, 281

  epidemiology and, 290

  see also cancer prevention

  procarbazine, 162, 164

  product-liability lawsuits, 269–73, 401

  progesterone, 456

  “Progress Against Cancer?” (Bailar and Smith), 229, 231–32, 329–30

  Prohibition, 262

  promyelocytes, 407–8, 409

  prostate, 211–13, 215

  prostate cancer, 211, 443

  in dogs, 212–13

  hormonal therapy for, 213–14, 222

  remissions in, 214

  surgical removal of, 59, 71, 216

  prostatectomy, radical, 71

  prostatic fluid, 211–12

  protein drugs, 414

  proteins, 345–46, 442

  as molecular switches, 387

  phosphorylation of, 358–59, 361, 380, 418, 431–32

  signaling pathways of, 387, 388, 389, 402, 406, 432, 443, 453–54, 457, 458, 464–65

  structural view of, 432

  protocols (clinical trials):

  for ABMT, 325–26

  for breast cancer, 200–201, 294–302, 420–22, 423, 424, 426–29

  for choriocarcinoma, 135–38, 139

  conflicts of interest in, 198

  for, CML, 436–38

  for Hodgkin’s lymphoma, 163–66, 208

  for leukemia, 132–34, 135, 139, 140–42, 143–50

  of mammography, 294–302

  multi-institutional, 207–8

  for palliative care, 226

  randomization in, 131–32, 160, 243, 293, 298–300, 302, 314, 319, 321, 426

  proto-oncogenes, 361–63, 364, 369, 370, 380, 384, 412

  activation of, 386–87, 388, 406, 407

  pteroylaspartic acid (PAA), 33

  public health and hygiene, 22

  Public Health Service, U.S., 257, 259, 260

  purines, 92

  pus, 13, 14

  radiation, 74–75

  as carcinogen, 75, 77–78, 347, 364, 389

  radiation therapy, 23, 154, 158–59, 405

  for breast cancer, 75–76, 77, 158, 161, 195, 464

  chemotherapy in combination with, 123–24, 154, 168–70, 400

  extended field, 159–61

  for Hodgkin’s lymphoma, 159–61, 163

  involved field, 160

  local surgery combined with, 195–96, 197, 464

  for lung cancer, 158, 403

  for lymphomas, 77, 158

  radium in, 76, 195

  staging and, 160–61

  X-rays in, 75–76, 158–59

  radical surgery, 6, 59, 60, 304, 308, 406

  see also mastectomies, radical

  radio, see broadcast media

  radium:

  discovery of, 74–75, 76

  radiation poisoning from, 74–75, 77–78, 173, 347

  in radiation therapy, 76, 195

  Radium girls, 78, 278

  Ramazzini, Bernardino, 238

  Ramses V, King of Egypt, 41

  randomization of trials and studies, 131–32, 160, 243, 247, 293, 294, 302, 314, 319, 321, 426

  ras gene, 374–75, 376, 379–80, 383, 384, 385, 387, 388, 391, 410, 412, 431n, 453–54, 458

  Ras-Mek-Erk pathway, 387, 453–54

  Rauscher, Frank, 191, 223, 234

  Rb gene, 364, 367–69, 376, 377–80, 381, 391, 412, 453–54, 458

  Reader’s Digest, 112

  recall bias, 446

  receptors, 31

  in estrogen, 215, 216, 217, 464

  recombinant DNA, 413, 414

  red blood cells, 3, 18, 88

  Red Queen syndrome, cancer and, 443, 444, 446, 470

  Reed, Carla, 1–3, 7, 17–18, 126–27, 168–69, 190, 337, 338–39, 398, 400, 448–49, 459

  Reimann, Stanley, 121–22

  relapses, 59, 138, 443

  of breast cancer, 64, 66–69, 197, 208, 221, 329, 419

  of leukemia, 35, 91, 132, 133, 147, 165, 166, 170, 442

  remissions:

  of ALL, 127, 190, 338–39, 400

  of APL, 409–10

  of breast cancer, 217, 222, 314, 454, 456

  of Hodgkin’s lymphoma, 160–61, 171, 179

  of leukemia, 34, 35, 101, 127, 133, 145–46, 179, 190

  of, CML, 437–39, 441, 443, 444

  retinoblastoma, 366–68, 376, 377, 380, 391

  retinoic acid, 408–9

  retroviruses, 318, 352, 353, 354, 360, 361–62, 363, 380

  as carcinogens, 354, 355–56, 357, 415, 431n

  reverse transcriptase, 352–54, 371

  Revlimid, 443

  Rhoads, Cornelius “Dusty,” 92, 114

  Richards, A. N., 121

  Richardson, Dora, 216

  Rieff, David, 306

  risk factors, for disease, 444–45

  for cancer, 44, 276, 303, 445–46, 455–57

  in social networks, 445–46

  risky prediction, 370

  R. J. Reynolds, 273

  RNA (ribonucleic acid), 91, 345–46

  reverse transcription to DNA of, 352–54, 371

  transcription from DNA to, 352

  viral, 352–54

  Roe v. Wade, 199

  Rogers, Paul, 187–88

  Rollin, Betty, 200

  Rome, ancient, medical knowledge in, 48–49

  Romeo and Juliet (Shakespeare), 89

  Röntgen, Anna, 73

  Röntgen, Wilhelm, 73–74

  Roosevelt, Franklin D., 25, 94, 404

  Rosenberg, Barnett, 204

  Rosenberg, C. E., 46

  Rosenow, Fanny, 26–27

  Rosensohn, Etta, 286

  Roswell Park Cancer Institute, 133, 167n

  Rous, Peyton, 173, 174, 175, 176, 335, 342–43, 350, 355, 362, 382, 383

  Rous sarcoma virus (RSV), 174, 342, 349–50, 351, 358–59, 372, 466

  genome as modified by, 351–52

  as mutated src gene, 361–62

  as retrovirus, 353

  Rowley, Janet, 365–66, 376, 409–10, 430–31

  Rubin, Harry, 351

  Ruijin Hospital, 408, 409–10

  Sabin, Albert, 22, 94

  St. Bartholomew’s Hospital, 195

  St. Christopher’s hospice, 225

  St. Jude’s hospital, 167–68, 170

  Saint Louis Hospital (Paris), 408

  St. Luke’s Hospital, 64

  St. Thomas’ Hospital, 156, 157

  Salecl, Renata, 182

  Salk, Jonas, 22, 94

  Salmonella, 277, 278

  Salomon, Albert, 290

  Salvarsan (compound 606), 86

  Samuel, Book of, 305

  Sandler, Elliott, 33, 34

  Sandler, Robert, 32–34, 35

  San Francisco, Calif., AIDS in, 317–18

  San Francisco General Hospital, Ward 5B at, 317–18, 424

  sarcomas, 173, 174, 443, 467

  SARS, 182

  Saunders, Cecily, 225–26

  Sawyers, Charles, 436, 437, 438, 441–42

  Schabel, Frank, 312

  Scheele, Leonard, 235

  Schleiden, Matthias, 15

  Schmidt, Benno, 184–85, 187

  Schope, Richard, 174

  Schuman, Leonard, 261

  Schwann, Theodor, 15

  science:

  Apollo program and public perception of, 179

  goal-driven vs. basic research in, 119–22, 183

  measurement in, 19, 74, 197–98, 227

  technology vs., 462

  Science the Endless Frontier (Bush), 120

  Scientific American, 227–28, 350

  scientific revolutions, 196

  screening:

  for breast cancer, 457, 464; see also mammography<
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  colonoscopy, 331, 401

  molecular biology and, 457–58

  over- vs. underdiagnosis in, 291–92, 293, 302

  Pap smears, 288–90, 296, 303, 331, 401

  as prone to error, 302

  scrofula, 47

  scrotal cancer, 173, 237–39, 241, 276

  scurvy, 110

  sea urchins, 341, 348, 349

  secondhand smoke, 260

  Senate, U.S., 122, 185

  see also Congress, U.S.

  Shakespeare, William, 1, 89, 191

  Shapiro, Sam, 294–95, 296, 297, 299, 302

  Shelby County, Tenn., 289–90

  Shepard, Mike, 418, 420, 427

  Sheridan, Catherine Variety, 95, 96

  Shih, Chiaho, 373–74, 376

  Shimkin, Michael, 107

  Shinder, Jason, 398

  signaling pathways, 387, 388, 389, 402, 406, 432, 443, 453–54, 457, 458, 464–65

  Silent Spring (Carson), 456

  6-mp (6-mercaptopurine), 92, 127, 132–33, 140, 143, 338

  see also VAMP regimen

  Skipper, Howard, 139, 140–41, 143, 196, 206, 311–12

  Skolnick, Mark, 381

  Slamon, Dennis, 415–19, 433

  Herceptin trials of, 420–22, 423, 426–29

  sleeping sickness, 85, 245

  slime molds, 345, 346, 349

  smallpox, 24, 41, 175, 225, 343

  Smith, Anna Deavere, 305

  Smith, Edwin, 39

  Smith, Elaine, 229, 231–34

  Smith papyrus, 39–41

  smoking, 45, 250, 251, 267–68, 272, 273–74, 275, 445–46

  cancer and, see tobacco-cancer link

  decrease in, 401

  increase in, 240–42, 445

  social networks and, 445–46

  by women, 268, 445

  see also cigarettes; nicotine; tobacco; tobacco industry

  Smoking and Cancer (Graham), 257

  “Smoking and Carcinoma of the Lung” (Doll and Hill), 246

  snuff, 239–40

  social networks, as risk factors for disease, 445–46

  Solzhenitsyn, Aleksandr, 4, 181, 316, 461

  Sontag, Susan, vii, 37–38, 202, 306, 316, 388, 449

  soot, 173, 238, 239, 364

  Sophocles, 321

  Sorenson, Beatrice, 153–55

  Special Virus Cancer Program, 175–76, 280–81, 356, 357

  specificity, specific affinity, 80–81, 84–88, 90–92, 210, 222, 432, 433, 434, 439

  Spector, Deborah, 361

  Speyer, Maria, 17

  Spiegelman, Sol, 186, 355–56, 357, 360, 362

  spinal fluid:

  chemotherapy and, 167–68

  leukemia in, 146–47

  spinal taps, 127, 146

  spleen, leukemia and, 14

  src gene, 375, 418, 431, 433

  endogenous, 361–62, 364, 368, 371, 466

  viral, 358–60, 364, 368, 370, 372

  stages, staging, of cancers, 55, 67, 160–61, 163, 164–65, 218, 222, 289, 290, 385, 428, 463

  STAMP (Solid Tumor Autologous Marrow Program) protocol, 310, 311–15, 320, 325, 326, 328–29

  as adjuvant therapy, 320

  Statistical Unit, 245

 

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