Siddhartha Mukherjee - The Emperor of All Maladies: A Biography of Cancer

by Siddhartha Mukherjee

  206 Adriamycin, discovered in 1969: F. Arcamone et al., "Adriamycin, 14-hydroxydaimomycin, a New Antitumor Antibiotic from S. Peucetius var. caesius," Biotechnology and Bioengineering 11, no. 6 (1969): 1101-10.

  206 could irreversibly damage the heart: C. A. J. Brouwer et al., "Long-Term Cardiac Follow-Up in Survivors of a Malignant Bone Tumor," Annals of Oncology 17, no. 10 (2006): 1586-91.

  206 Etoposide came from the fruit: A. M. Arnold and J. M. A. Whitehouse, "Etoposide: A New Anti-cancer Agent," Lancet 318, no. 8252 (1981): 912-15.

  206 Bleomycin, which could scar lungs without warning: H. Umezawa et al., "New Antibiotics, Bleomycin A and B," Journal of Antibiotics (Tokyo) 19, no. 5 (1966): 200-209; Nuno R. Grande et al., "Lung Fibrosis Induced by Bleomycin: Structural Changes and Overview of Recent Advances," Scanning Microscopy 12, no. 3 (1996): 487-94; R. S Thrall et al., "The Development of Bleomycin-Induced Pulmonary Fibrosis in Neutrophil-Depleted and Complement-Depleted Rats," American Journal of Pathology 105 (1981): 76-81.

  207 "Did we believe we were going to cure cancer": George Canellos, interview with author.

  207 In the mid-1970s: J. Ziegler, I. T. McGrath, and C. L. Olweny, "Cure of Burkitt's Lymphoma--Ten-Year Follow-Up of 157 Ugandan Patients," Lancet 3, no. 2 (8149) (1979): 936-38. Also see Ziegler et al., "Combined Modality Treatment of Burkitt's Lymphoma," Cancer Treatment Report 62, no. 12 (1978): 2031-34.

  207 "Our applications skyrocketed": Ibid.

  207 "There is no cancer that is not potentially curable": "Cancer: The Chill Is Still There," Los Angeles Times, March 20, 1979.

  208 the eight-in-one study: J. Russel Geyer et al., "Eight Drugs in One Day Chemotherapy in Children with Brain Tumors: A Critical Toxicity Appraisal," Journal of Clinical Oncology 6, no. 6 (1988): 996-1000.

  209 "When doctors say that the side effects are tolerable": "Some Chemotherapy Fails against Cancer," New York Times, August 6, 1985.

  209 "The smiling oncologist": Rose Kushner, "Is Aggressive Adjuvant Chemotherapy the Halsted Radical of the '80s?" 1984, draft 9, Rose Kushner papers. The phrase was deleted in the final text that appeared in 1984.

  209 "Hexamethophosphacil with Vinplatin to potentiate": Edson, Wit, 31.

  Knowing the Enemy

  210 It is said that if you know your enemies: Sun Tzu, The Art of War (Boston: Shambhala, 1988), 82.

  210 a urological surgeon, Charles Huggins: Luis H. Toledo-Pereyra, "Discovery in Surgical Investigation: The Essence of Charles Brenton Huggins," Journal of Investigative Surgery 14 (2001): 251-52; Robert E. Forster II, "Charles Brenton Huggins (22 September 1901-12 January 1997)," Proceedings of the American Philosophical Society 143, no. 2 (1999): 327-31.

  211 Huggins's studies of prostatic fluid: C. Huggins et al., "Quantitative Studies of Prostatic Secretion: I. Characteristics of the Normal Secretion; the Influence of Thyroid, Suprarenal, and Testis Extirpation and Androgen Substitution on the Prostatic Output," Journal of Experimental Medicine 70, no. 6 (1939): 543-56; Charles Huggins, "Endocrine-Induced Regression of Cancers." Science 156, no. 3778 (1967): 1050-54; Tonse N. K. Raju, "The Nobel Chronicles. 1966: Francis Peyton Rous (1879-1970) and Charles Brenton Huggins (1901-1997), Lancet 354, no. 9177 (1999): 520.

  212 "It was vexatious to encounter a dog": Huggins, "Endocrine-Induced Regression."

  213 "Cancer is not necessarily autonomous": Ibid.

  213 "Its growth can be sustained and propagated": Ibid.

  213 In 1929, Edward Doisy, a biochemist: Edward A. Doisy, "An Autobiography," Annual Review of Biochemistry 45 (1976): 1-12.

  213 diethylstilbestrol (or DES): E. C. Dodds et al., "Synthetic Oestrogenic Compounds Related to Stilbene and Diphenylethane. Part I," Proceedings of the Royal Society of London, Series B, Biological Sciences 127, no. 847 (1939): 140-67; E. C. Dodds et al., "Estrogenic Activity of Certain Synthetic Compounds," Nature 141, no. 3562 (1938): 247-48; Edward Charles Dodds, Biochemical Contributions to Endocrinology: Experiments in Hormonal Research (Palo Alto, CA: Stanford University Press, 1957); Robert Meyers, D.E.S., the Bitter Pill (New York: Seaview/Putnam, 1983).

  213 Premarin, natural estrogen purified: Barbara Seaman, The Greatest Experiment Ever Performed on Women: Exploding the Estrogen Myth (New York: Hyperion, 2004), 20-21.

  213 he could inject them to "feminize" the male body: Huggins, "Endocrine-Induced Regression"; Charles Huggins et al., "Studies on Prostatic Cancer: II. The Effects of Castration on Advanced Carcinoma of the Prostate Gland," Archives of Surgery 43 (1941): 209-23.

  214 George Beatson and breast cancer: George Thomas Beatson, "On the Treatment of Inoperable Cases of Carcinoma of the Mamma: Suggestions for a New Method of Treatment, with Illustrative Cases," Lancet 2 (1896): 104-7; Serena Stockwell, "George Thomas Beatson, M.D. (1848-1933)," CA: A Cancer Journal for Clinicians 33 (1983): 105-7.

  214 only about two-thirds of all women: Alexis Thomson, "Analysis of Cases in Which Oophorectomy was Performed for Inoperable Carcinoma of the Breast," British Medical Journal 2, no. 2184 (1902): 1538-41.

  214 "It is impossible to tell beforehand": Ibid.

  215 a young chemist in Chicago: E. R. DeSombre, "Estrogens, Receptors and Cancer: The Scientific Contributions of Elwood Jensen," Progress in Clinical and Biological Research 322 (1990): 17-29; E. V. Jensen and V. C. Jordan, "The Estrogen Receptor: A Model for Molecular Medicine," Clinical Cancer Research 9, no. 6 (2003): 1980-89.

  215 Ovarian removal produced many other severe side effects: R. Sainsbury, "Ovarian Ablation as a Treatment for Breast Cancer," Surgical Oncology 12, no. 4 (2003): 241-50.

  216 "there was little enthusiasm": Jensen and Jordan, "The Estrogen Receptor."

  216 Tamoxifen: Walter Sneader, Drug Discovery: A History (New York: John Wiley and Sons, 2005), 198-99; G. R. Bedford and D. N. Richardson, "Preparation and Identification of cis and trans Isomers of a Substituted Triarylethylene," Nature 212 (1966): 733-34.

  216 Originally invented as a birth control pill: M. J. Harper and A. L. Walpole, "Mode of Action of I.C.I. 46,474 in Preventing Implantation in Rats," Journal of Endocrinology 37, no. 1 (1967): 83-92.

  216 tamoxifen had turned out to have exactly the opposite effect: A. Klopper and M. Hall, "New Synthetic Agent for Induction of Ovulation: Preliminary Trials in Women," British Medical Journal 1, no. 5741 (1971): 152-54.

  216 Arthur Walpole and breast cancer: V. C. Jordan, "The Development of Tamoxifen for Breast Cancer Therapy: A Tribute to the Late Arthur L. Walpole," Breast Cancer Research and Treatment 11, no. 3 (1988): 197-209.

  216 Mary Cole's tamoxifen trial: M. P. Cole et al., "A New Anti-oestrogenic Agent in Late Breast Cancer: An Early Clinical Appraisal of ICI46474," British Journal of Cancer 25, no. 2 (1971): 270-75; Sneader, Drug Discovery, 199.

  217 In 1973, V. Craig Jordan: See V. C. Jordan, Tamoxifen: A Guide for Clinicians and Patients (Huntington, NY: PRR, 1996). Also see V. C. Jordan, "Effects of Tamoxifen in Relation to Breast Cancer," British Medical Journal 6075 (June 11, 1977): 1534-35.

  Halsted's Ashes

  218 I would rather be ashes: Jack London, Tales of Adventure (Fayetteville, AR: Hannover House, 1956), vii.

  218 Will you turn me out: Cicely Saunders, Selected Writings, 1958-2004, 1st ed. (Oxford: Oxford University Press, 2006), 71.

  219 at the NCI, Paul Carbone, had launched a trial: Vincent T. DeVita, "Paul Carbone: 1931-2002," Oncologist 7, no. 2 (2002): 92-93.

  219 "Except for an occasional woman": Paul Carbone, "Adjuvant Therapy of Breast Cancer 1971-1981," Breast Cancer Research and Treatment 2 (1985): 75-84.

  220 With his own trial, the NSABP-04: B. Fisher et al., "Comparison of Radical Mastectomy with Alternative Treatments for Primary Breast Cancer. A First Report of Results from a Prospective Randomized Clinical Trial," Cancer 39 (1977): 2827-39.

  220 In 1972, as the NCI was scouring the nation: G. Bonadonna et al., "Combination Chemotherapy as an Adjuvant Treatment in Operable Breast Cancer," New England Journal of Medicine 294, no. 8 (1976): 405-10; Vincent T. DeVita Jr. and Edward C
hu, "A History of Cancer Chemotherapy," Cancer Research 68, no. 21 (2008): 8643-53.

  220 "The surgeons were not just skeptical": Springer, European Oncology Leaders (Berlin, 2005), 159-65.

  221 Fisher's tamoxifen trial: B. Fisher et al., "Adjuvant Chemotherapy with and without Tamoxifen in the Treatment of Primary Breast Cancer: 5-Year Results from the National Surgical Adjuvant Breast and Bowel Project Trial," Journal of Clinical Oncology 4, no. 4 (1986): 459-71.

  223 "We were all more naive a decade ago": "Some Chemotherapy Fails against Cancer," New York Times, August 6, 1985.

  223 "We shall so poison the atmosphere of the first act": James Watson, New York Times, May 6, 1975.

  225 "If there is persistent pain": J. C. White, "Neurosurgical Treatment of Persistent Pain," Lancet 2, no. 5 (1950): 161-64.

  225 "a window in [her] home": Saunders, Selected Writings, xiv.

  225 care, she wrote, "is a soft word": ibid., 255.

  225 "The resistance to providing palliative care to patients": Nurse J. N. (name withheld), interview with author, June 2007.

  226 "The provision of . . . terminal care: Saunders, Selected Writings, 71.

  Counting Cancer

  227 We must learn to count the living: Audre Lourde, The Cancer Journals, 2nd ed. (San Francisco: Aunt Lute, 1980), 54.

  227 Counting is the religion of this generation: Gertrude Stein, Everybody's Autobiography (New York: Random House, 1937), 120.

  227 "These registries," Cairns wrote in an article: John Cairns, "Treatment of Diseases and the War against Cancer," Scientific American 253, no. 5 (1985): 51-59.

  229 John Bailar and Elaine Smith's analysis: J. C. Bailar III and E. M. Smith, "Progress against Cancer?" New England Journal of Medicine 314, no. 19 (1986): 1226-32.

  231 cancer mortality was not declining: This was not unique to the United States; the statistics were similarly grim across Europe. In 1985, a separate analysis of age-adjusted cancer mortality across twenty-eight developed countries revealed an increase in cancer mortality of about 15 percent.

  231 There is "no evidence": Bailar and Smith, "Progress against Cancer?"

  231 "a thorn in the side of the National Cancer Institute": Gina Kolata, "Cancer Progress Data Challenged," Science 232, no. 4753 (1986): 932-33.

  232 As evidence, they pointed to a survey: See E. M. Greenspan, "Commentary on September 1985 NIH Consensus Development Conference on Adjuvant Chemotherapy for Breast Cancer," Cancer Investigation 4, no. 5 (1986): 471-75. Also see Ezra M. Greenspan, letter to the editor, New England Journal of Medicine 315, no. 15 (1986): 964.

  232 "The problem with reliance on a single measure": Lester Breslow and William G. Cumberland, "Progress and Objectives in Cancer Control," Journal of the American Medical Association 259, no. 11 (1988): 1690-94.

  233 "Our purpose in making these calculations": Ibid. The order of the quotation has been inverted for the purpose of this narrative.

  234 prevention research received: John Bailar interviewed by Elizabeth Farnsworth, "Treatment versus Prevention" (transcript), NewsHour with Jim Leher, PBS, May 29, 1997; Richard M. Scheffler and Lynn Paringer, "A Review of the Economic Evidence on Prevention," Medical Care 18, no. 5 (1980): 473-84.

  234 By 1992, this number had increased: Samuel S. Epstein, Cancer-Gate: How to Win the Losing Cancer War (Amityville, NY: Baywood Publishing Company, 2005), 59.

  234 In 1974, describing to Mary Lasker: Letter from Frank Rauscher to Mary Lasker, March 18, 1974, Mary Lasker Papers, Box 118, Columbia University.

  234 At Memorial Sloan-Kettering in New York: Ralph W. Moss, The Cancer Syndrome (New York: Grove Press, 1980), 221.

  234 "not one" was able to suggest an "idea": Edmund Cowdry, Etiology and Prevention of Cancer in Man (New York: Appleton-Century, 1968), xvii.

  234 Prevention, he noted drily: Moss, The Cancer Syndrome, 221.

  234 "A shift in research emphasis": Bailar and Smith, "Progress against Cancer?"

  PART FOUR:

  PREVENTION IS THE CURE

  235 It should first be noted: David Cantor, "Introduction: Cancer Control and Prevention in the Twentieth Century," Bulletin of the History of Medicine 81 (2007): 1-38.

  235 The idea of preventive medicine: "False Front in War on Cancer," Chicago Tribune, February 13, 1975.

  235 The same correlation could be drawn: Ernest L. Wynder letter to Evarts A. Graham, June 20, 1950, Evarts Graham papers.

  "Coffins of black"

  237 When my mother died I was very young: "The Chimney Sweeper," William Blake, The Complete Poetry and Prose of William Blake, ed. David V. Erdman (New York: Random House, 1982), 10.

  237 It is a disease, he wrote: Percivall Pott and James Earles, The Chirurgical Works of Percivall Pott, F.R.S. Surgeon to St. Bartholomew's Hospital, a New Edition, with His Last Corrections, to Which Are Added, a Short Account of the Life of the Author, a Method of Curing the Hydrocele by Injection, and Occasional Notes and Observations, by Sir James Earle, F.R.S. Surgeon Extraordinary to the King (London: Wood and Innes, 1808), 3: 177.

  238 "Syphilis," as the saying ran: Michael J. O'Dowd and Elliot E. Philipp, The History of Obstetrics & Gynaecology (New York: Parthenon Publishing Group, 2000), 228.

  238 In 1713, Ramazzini had published: Bernardino Ramazzini, De Morbis Artificum Diatriba (Apud Josephum Corona, 1743).

  238 "All this makes it (at first) a very different case": Pott and Earles, Chirurgical Works, 3: 177.

  239 Eighteenth-century England: See Peter Kirby, Child Labor in Britain, 1750-1870 (Hampshire, UK: Palgrave Macmillan, 2003). For details on chimney sweeps, see ibid., 9; and Parliamentary Papers 1852-52, 88, pt. 1, tables 25, 26.

  239 "I wants a 'prentis": Charles Dickens, Oliver Twist, or The Parish Boy's Progress (London: J. M. Dent & Sons, 1920), 16.

  239 In 1788, the Chimney Sweepers Act: Joel H. Wiener, Great Britain: The Lion at Home: A Documentary History of Domestic Policy, 1689-1973 (New York: Chelsea House Publishers, 1974), 800.

  239 In 1761, more than a decade before: John Hill, Cautions against the Immoderate Use of Snuff (London: R. Baldwin and J. Jackson, 1761).

  240 a self-professed "Bottanist, apothecary, poet": G. S. Rousseau, ed. The Letters and Papers of Sir John Hill, 1714-1775 (New York: AMS Press, 1982), 4.

  240 "close, clouded, hot, narcotic rooms": George Crabbe, The Poetical Works of the Rev. George Crabbe: With his Letters and Journals, and His Life (London: John Murray, 1834), 3: 180.

  240 By the mid-1700s, the state of Virginia: See Paul G. E. Clemens, "From Tobacco to Grain," Journal of Economic History 35, no. 1: 256-59.

  240 In England the import of tobacco: Kenneth Morgan, Bristol and the Atlantic Trade in the Eighteenth Century (Cambridge University Press, 1993), 152.

  240 In 1855, legend runs, a Turkish soldier: See Richard Klein, Cigarettes Are Sublime (Durham, NC: Duke University Press, 1993), 134-35.

  240 In 1870, the per capita consumption in America: Jack Gottsegen, Tobacco: A Study of Its Consumption in the United States (New York: Pittman, 1940).

  241 A mere thirty years later, Americans: Ibid.

  241 On average, an adult American smoked ten cigarettes: Harold F. Dorn, "The Relationship of Cancer of the Lung and the Use of Tobacco," American Statistician 8, no. 5 (1954): 7-13.

  241 By the early twentieth century, four out of five: Richard Peto, interview with author, September 2008.

  241 "By the early 1940s, asking about a connection": Ibid.

  242 "So has the use of nylon stockings": John Wilds and Ira Harkey, Alton Ochsner, Surgeon of the South (Baton Rouge: Louisiana State University Press, 1990), 180.

  242 "the cigarette century": Allan M. Brandt, The Cigarette Century: The Rise, Fall, and Deadly Persistence of the Product That Defined America (New York: Basic Books, 2007).

  The Emperor's Nylon Stockings

  243 Whether epidemiology alone can: Sir Richard Doll, "Proof of Causality: Deduction from Epidemiological Observation," Perspectives in Biology and Medicine 45 (2002): 49
9-515.

  243 lung cancer morbidity had risen nearly fifteenfold: Richard Doll and A. Bradford Hill, "Smoking and Carcinoma of the Lung," British Medical Journal 2, no. 4682 (1950): 739-48.

  243 "matter that ought to be studied": Richard Peto, "Smoking and Death: The Past 40 Years and the Next 40," British Medical Journal 309 (1994): 937-39.

  243 In February 1947, in the midst of a bitterly cold: Ibid.

  243 One expert, having noted parenthetically: British Public Records Office, file FD. 1, 1989, as quoted by David Pollock, Denial and Delay (Washington, DC: Action on Smoking and Health, 1989); full text available through Action on Smoking and Health, www.ash.org.

  243 Yet the resources committed for the study: Medical Research Council 1947/366 and Ibid.

  244 In the summer of 1948: Pollock, Denial and Delay, prologue. Also see Sir Richard Doll, "The First Report on Smoking and Lung Cancer," in Ashes to Ashes: The History of Smoking and Health, Stephen Lock, Lois A. Reynolds, and E. M. Tansey, eds. (Amsterdam: Editions Rodopi B.V., 1998), 129-37.

  244 "The same correlation could be drawn to the intake of milk": Ernst L. Wynder, letter to Evarts A. Graham, June 20, 1950, Evarts Graham papers.

  245 Wynder and Graham's trial: Ernst L. Wynder and Evarts A. Graham, "Tobacco Smoking as a Possible Etiologic Factor in Bronchiogenic Carcinoma: A Study of Six Hundred and Eighty-Four Proved Cases," Journal of the American Medical Association 143 (1950): 329-38.

  245 When Wynder presented his preliminary ideas: Ernst L. Wynder, "Tobacco as a Cause of Lung Cancer: Some Reflections," American Journal of Epidemiology 146 (1997), 687-94. Also see Jon Harkness, "The U.S. Public Health Service and Smoking in the 1950s: The Tale of Two More Statements," Journal of the History of Medicine and Allied Sciences 62, no. 2 (2007): 171-212.

  245 Doll and Hill's study: Doll and Hill, "Smoking and Carcinoma of the Lung."

  246 When the price of cigarettes was increased: Richard Peto, personal interview. Also see Virginia Berridge, Marketing Health: Smoking and the Discourse of Public Health in Britain (Oxford: Oxford University Press, 2007), 45.