SCRIBNER A Division of Simon & Schuster, Inc 1230 Avenue of the Americas New York, NY 10020 www.SimonandSchuster.com Copyright © 2010 by Siddhartha Mukherjee, M.D All rights reserved, including the right to reproduce this book or portions thereof in any form whatsoever For information address Scribner Subsidiary Rights Department, 1230 Avenue of the Americas, New York, NY 10020 First Scribner hardcover edition November 2010 SCRIBNER and design are registered trademarks of The Gale Group, Inc., used under license by Simon & Schuster, Inc., the publisher of this work For information about special discounts for bulk purchases, please contact Simon & Schuster Special Sales at 1-866-506-1949 or business@simonandschuster.com The Simon & Schuster Speakers Bureau can bring authors to your live event For more information or to book an event contact the Simon & Schuster Speakers Bureau at 1-866-248-3049 or visit our website at www.simonspeakers.com Manufactured in the United States of America 10 Library of Congress Control Number: 2010024114 ISBN 978-1-4391-0795-9 ISBN 978-1-4391-8171-3 (ebook) Photograph credits appear on page 543 To ROBERT SANDLER (1945–1948), and to those who came before and after him Illness is the night-side of life, a more onerous citizenship Everyone who is born holds dual citizenship, in the kingdom of the well and in the kingdom of the sick Although we all prefer to use only the good passport, sooner or later each of us is obliged, at least for a spell, to identify ourselves as citizens of that other place —Susan Sontag Contents Author’s Note Prologue Part One: “Of blacke cholor, without boyling” Part Two: An Impatient War Part Three: “Will you turn me out if I can’t get better?” Part Four: Prevention Is the Cure Part Five: “A Distorted Version of Our Normal Selves” Part Six: The Fruits of Long Endeavors Atossa’s War Acknowledgments Notes Glossary Selected Bibliography Photograph Credits Index In 2010, about six hundred thousand Americans, and more than million humans around the world, will die of cancer In the United States, one in three women and one in two men will develop cancer during their lifetime A quarter of all American deaths, and about 15 percent of all deaths worldwide, will be attributed to cancer In some nations, cancer will surpass heart disease to become the most common cause of death Author’s Note This book is a history of cancer It is a chronicle of an ancient disease—once a clandestine, “whispered-about” illness—that has metamorphosed into a lethal shape-shifting entity imbued with such penetrating metaphorical, medical, scientific, and political potency that cancer is often described as the defining plague of our generation This book is a “biography” in the truest sense of the word— an attempt to enter the mind of this immortal illness, to understand its personality, to demystify its behavior But my ultimate aim is to raise a question beyond biography: Is cancer’s end conceivable in the future? Is it possible to eradicate this disease from our bodies and societies forever? The project, evidently vast, began as a more modest enterprise In the summer of 2003, having completed a residency in medicine and graduate work in cancer immunology, I began advanced training in cancer medicine (medical oncology) at the Dana-Farber Cancer Institute and Massachusetts General Hospital in Boston I had initially envisioned writing a journal of that year—a view-from-the-trenches of cancer treatment But that quest soon grew into a larger exploratory journey that carried me into the depths not only of science and medicine, but of culture, history, literature, and politics, into cancer’s past and into its future Two characters stand at the epicenter of this story—both contemporaries, both idealists, both children of the boom in postwar science and technology in America, and both caught in the swirl of a hypnotic, obsessive quest to launch a national “War on Cancer.” The first is Sidney Farber, the father of modern chemotherapy, who accidentally discovers a powerful anti-cancer chemical in a vitamin analogue and begins to dream of a universal cure for cancer The second is Mary Lasker, the Manhattan socialite of legendary social and political energy, who joins Farber in his decades-long journey But Lasker and Farber only exemplify the grit, imagination, inventiveness, and optimism of generations of men and women who have waged a battle against cancer for four thousand years In a sense, this is a military history—one in which the adversary is formless, timeless, and pervasive Here, too, there are victories and losses, campaigns upon campaigns, heroes and hubris, survival and resilience—and inevitably, the wounded, the condemned, the forgotten, the dead In the end, cancer truly emerges, as a nineteenth-century surgeon once wrote in a book’s frontispiece, as “the emperor of all maladies, the king of terrors.” A disclaimer: in science and medicine, where the primacy of a discovery carries supreme weight, the mantle of inventor or discoverer is assigned by a community of scientists and researchers Although there are many stories of discovery and invention in this book, none of these establishes any legal claims of primacy This work rests heavily on the shoulders of other books, studies, journal articles, memoirs, and interviews It rests also on the vast contributions of individuals, libraries, collections, archives, and papers acknowledged at the end of the book One acknowledgment, though, cannot be left to the end This book is not just a journey into the past of cancer, but also a personal journey of my coming-of-age as an oncologist That second journey would be impossible without patients, who, above and beyond all contributors, continued to teach and inspire me as I wrote It is in their debt that I stand forever This debt comes with dues The stories in this book present an important challenge in maintaining the privacy and dignity of these patients In cases where the knowledge of the illness was already public (as with prior interviews or articles) I have used real names In cases where there was no prior public knowledge, or when interviewees requested privacy, I have used a false name, and deliberately confounded identities to make it difficult to track them However, these are real patients and real encounters I urge all my readers to respect their identities and boundaries 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, Percivall, 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 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 statistics: negative claims in, 197–98 normalization in, 230–31; see also age-adjusting staurosporine, 432 Stehelin, Dominique, 361 Stein, Gertrude, 227 stem cells, 398, 458 sterility, as side effect of chemotherapy, 165 Sternberg, Carl, 157 steroids, 103 stomach cancer, 44–45, 381, 456 neurotic stress blamed for, 281 Strax, Philip, 294–95, 296, 297, 299 streptomycin, 22, 131–32 stroke, 444 Study in Scarlet, A (Doyle), SU11248, 468 Subbarao, Yellapragada “Yella,” 30–31, 33, 34, 35, 87, 91 sulfa drugs, 110 Sun Tzu, 210 Supreme Court, U.S., 266 surgeon general, U.S., 259–60 smoking-health report of, 260–62, 264, 267, 401 surgeons: as hostile to chemotherapy, 219–21 self-confidence of, 66, 308 surgery, 355, 405 abdominal, 58 for breast cancer, 58, 62, 195–96, 197, 201, 402; see also mastectomies evolution of, 55, 61–62, 66 infection as risk of, 56–57 local, combined with radiation therapy, 195–96, 197, 464 for lung cancer, 59, 72, 256 as performance, 66 radical, see mastectomies, radical; radical surgery removal of tumors through, 41, 49–50, 55, 58–59 survival rates, bias in, 229–30 SV 40, 349n Sweden: ABMT trial in, 326 mammography trials in, 298, 300–301 Swinburne, Algernon Charles, 461 Sylvester, Robert, 34 Symington, Stuart, 186 syphilis, 86, 157, 238 Tabin, Cliff, 383 Taft, William Howard, 24–25 Talman, William, 266–67 Talpaz, Moshe, 436, 437, 438, 441, 442 tamoxifen, 216–17, 218, 221–22, 407, 456, 457, 464, 466 Tarceva, 455 targeted therapies, 405–11, 412, 443, 455 for APL, 407–10 for breast cancer, 413–22, 454, 464, 465 for, CML, 430–40, 441–43 Tatum, Edward, 345 Taxol, 206, 403–4, 427–28 technology, 466 medicine as, 462 television, see broadcast media Temecula, Calif., 321–22, 324 Temin, Howard, 350–55, 357–58, 359, 361–62, 371, 372 Tenth International Cancer Congress, 353–54 teratoma, 152 Terry, Luther, 259–60, 262–63 testicular cancer, 181, 204–5, 208, 228, 331, 401 testosterone, 212–13, 214, 215 tetracycline, 22 thalidomide, 199, 443 thioguanine, 127 Thomas, E Donnall, 309, 434 Thomas, Lewis, 430 Thomas Aquinas, Saint, 393 Thoreau, Henry David, 38 Through the Looking-Glass (Carroll), 441, 443 thymoma, 152 thyroid cancer, 152, 212 thyroid hormone, 212 Time, 22, 24, 25, 103, 178 tobacco: bacterial mutations caused by, 278 British addiction to, 240 oral cancers linked to, 239–40 U.S production of, 240 see also cigarettes; nicotine; smoking; tobacco industry tobacco-cancer link, 276, 290, 364, 388 antitobacco campaigns and, 401, 446 author’s encounters with, 274–75 causality dispute in, 253–56 Doll/Hill studies and, 245–49, 250–51, 253–54, 260, 262, 263, 276, 294, 350, 401, 455 J Hill’s pamphlet on, 239–40, 276 lag time in, 272 as obscured by prevalence of smoking, 241–42 public policy and, 257, 259–62 secondhand smoke and, 260 surgeon general’s report on, 260–62, 264, 267, 401 tobacco industry and, 250–53, 258, 259, 260, 264 Wynder/Graham study and, 244–45, 246–47, 252, 253–55, 256, 260, 263, 401 tobacco industry: advertising by, 250–51, 263–64, 265–67, 268, 273 developing countries targeted by, 273–74 government regulation of, 262–65, 273 Master Settlement Agreement and, 273 political power of, 259, 260, 264, 273 product-liability lawsuits against, 269–73, 401 public relations campaigns by, 250–53, 258, 266 women targeted by, 268 Tobacco Industry Research Committee (TIRC), 253, 264 Tobacco Research Institute, 270 tobacco tokens, 246 Tocqueville, Alexis de, 107–8 Todaro, George, 358n tongue cancer, 274 total therapy (chemotherapy plus radiation), 123–24, 154, 168–70 toxicity, of chemotherapy, 43–44, 168, 208, 305, 309, 320 traits, heritability of, 343–44, 364, 366 transfusions, 196, 280 transgenic mice, 382–83, 384 trans-retinoic acid, 408–10 Trastuzumab, see Herceptin Traut, Herbert, 288 Treponema pallidum, 86 Tripathy, Debu, 424 True cigarettes, 269 Truman, Harry, 117, 120 Truth or Consequences, 97–99 Trypanosoma gondii, 85 Trypan Red, 85 tuberculosis, 24, 41, 72, 84, 87, 157, 175, 256 in ancient world, 44 as iconic 19th century disease, 37–38, 45 mortality rates from, 229 naming of, 47 public hygiene and, 22 streptomycin and, 131–32 tumors, 16, 19 angiogenesis of, 387, 388, 389, 391, 407, 443, 458 Baillie’s descriptions of, 53–54 bone, 43 brain, 71–72 chemotherapy for, 122–23, 154, 207, 308–9 in Galenic theory, 48–49 malignant vs benign, 47, 56 metastasis of, 55, 67, 135, 136, 154, 195–96, 302–3, 389 premetastatic, 302–3 radiation therapy for, 76, 77, 154, 158–59 stages of, 55, 67, 160–61, 218 surgical removal of, 41, 49–50, 55, 58–59 see also specific cancers tumor suppressor genes, 368–69, 376, 380, 381, 384, 385, 402, 412, 450, 453 inactivation of, 386–87, 389, 391, 406, 407 Turner, Charlotte, 325 two-hit hypothesis, 367–69, 376, 377, 380 typhoid fever, 22, 24 typhus, 41, 46 Uganda, 204n Ullrich, Axel, 414–18, 420, 427, 433 umbilical blood, 398–99 Undark, 77 United Kingdom, see Great Britain uranium, 74 Urban, Jerome, 193, 198 urea, 83, 84 urological cancers, 71 U.S Radium, 77–78 uterine cancer, 59, 277, 306, 331 Uzbekistan, cigarette consumption in, 274 vaginal cancer, 277 VAMP regimen, 142, 143–50, 165, 310 consortium opposition to, 144 relapses and, 166 remissions and, 145–46 survivors of, 148–50 Zubrod’s opposition to, 143 Variety Club of New England, 95, 172 Varmus, Harold, 360–63, 364, 365, 369, 370, 371, 375, 380, 439 vectors, for infectious diseases, 245 Velcade (bortezomib), 443 Venet, Louis, 294–95, 296 Verghese, Abraham, 308 Veronesi, Umberto, 220 Vesalius, Andreas, 51–53, 54, 59, 211, 434, 455 Vietnam War, 187, 207 vinblastine, 205 vincristine (Oncovin), 127, 139–40, 143, 149, 162, 164, 406 see also VAMP regimen Virchow, Rudolf, 13–16, 18, 237, 340, 430, 431, 455 Virginia, tobacco production in, 240 Virginia Slims cigarettes, 267, 268–69 virology, virologists, 349–56, 357–62, 364, 371, 466 viruses: as carcinogens, 173, 174–76, 278–81, 303, 342–43, 349–50, 351–56, 362 RNA forms of, see retroviruses Visco, Frances, 426, 427, 429 vitalism, 83 vitamin B12, 28, 31 Vogelstein, Bert, 384–86, 448 Cancer Genome Atlas and, 450–54 Vogt, Peter, 358 Volberding, Paul, 317, 424 Volkmann, Richard von, 62, 64, 67 Voltaire, 143 von Hansemann, David Paul, 340–41, 366 Waksman, Selman, 122 Wall Street Journal, 181 Walpole, Arthur, 216, 304 Walters, Barbara, 186 Wang, Zhen Yi, 408–1 war gasses, 87–88, 89–90 Warm Springs Foundation, 94 War on Cancer, 121, 172–73, 313, 329, 330, 332, 350, 455 Apollo space program as analogous to, 178–79 defining success in, 461–63, 465 Farber and, 114, 118, 122, 150, 155, 178, 180, 184, 188, 190, 234 measuring progress in, 227, 231, 323–33 M Lasker and, 113–14, 117–18, 122, 155, 177–78, 179, 183–86, 188–89, 191, 234, 296, 402, 403 Nixon and, 180–81, 184, 187–88 Panel of Consultants in, 184, 188 Times ad in, 180–81, 183 Warren, Robin, 281–84, 456 Washington Post, 32, 73, 180–81 Watson, James, 89, 186–87, 393, 455 Weinberg, Robert, 355, 370–76, 379–80, 390–92, 410–11, 412, 413, 443 Weissman, George, 262 Welch, William, 63 Western General Hospital, 329 white blood cells (lymphocytes), 3, 13, 17, 29, 152, 407, 409 aminopterin and, 33–34 chemotherapy and, 127, 315 nitrogen mustard and, 88, 90 in response to infection, 13, 16 Whitehead Institute, 376–77, 379 Wiedrich, Bob, 187 Wigler, Michael, 374, 376 Williams, Ted, 102 Williams, William Carlos, 306 Wills, Lucy, 28, 29 Wilms’ tumor, 123–24 Wit (Edson), 205, 209 Witwatersrand, University of, 321, 323, 326, 327–28 Woglom, William, 80 Wöhler, Friedrich, 83–84 Wolfe, Thomas, 93 Wolff, James, 34 Wolfler, Anton, 62 women: cigarette advertising targeted to, 268 lung cancer mortality rate in, 331 smoking by, 268, 445 Women’s Field Army, 111, 113 Wood, Francis Carter, 46 Woodard, Frank, 108 Woodard, Sara Johnson, 108, 109–10 Worcester Foundation, 217 World War I: cigarette consumption increased by, 250 mustard gas in, 87–88 World War II, 26, 89, 109, 129 cigarette consumption increased by, 250 scientific research in, 119–20, 129–30 Wynder, Ernst, 250 tobacco-cancer study of, 244–45, 246–47, 252, 253–55, 256, 260, 263, 401 X-rays, 23, 44 as carcinogen, 77–78, 347, 349, 389 as diagnostic tool, 291; see also mammography discovery of, 73–74 DNA damaged by, 75, 77 mutation increased by, 278, 347 in radiation therapy, 75–76, 123–24, 127, 158–59 Yale–New Haven Hospital, 226 Yarborough, Ralph, 184 yellow bile, 48, 53 Young, Hugh Hampton, 71 Ypres, Belgium, 88 Ziegler, John, 207 Zimmermann, Jürg, 433, 435 Zubrod, Gordon, 129–30, 132, 134, 137–38, 139, 140, 147, 162, 163–64, 207, 260 leukemia research consortium created by, 130–31, 133 VAMP opposed by, 143 ... may have intended his absurdly totalitarian cancer hospital to parallel the absurdly totalitarian state outside it, yet when I once asked a woman with invasive cervical cancer about the parallel,... physically and emotionally grueling, but the first months of the fellowship flicked away those memories as if all of that had been child’s play, the kindergarten of medical training Cancer was an all- consuming... quest to launch a national “War on Cancer.” The first is Sidney Farber, the father of modern chemotherapy, who accidentally discovers a powerful anti-cancer chemical in a vitamin analogue and begins