The Emperor of All Maladies

  190 “Surely,” she wrote, “the world will never be the same”: Lasker, “A Personal Tribute.”

  PART THREE:

  “WILL YOU TURN ME OUT IF I CAN’T GET BETTER?”

  191 Oft expectation fails: William Shakespeare, All’s Well That Ends Well (New York: Macmillan, 1912), act 2, scene 1, lines 145–47, p. 34.

  191 I have seen the moment of my greatness flicker: T. S. Eliot, “The Love Song of J. Alfred Prufrock,” lines 84–86, The Norton Anthology of Poetry, 4th ed. (New York: Norton, 1996), 1232.

  191 You are absolutely correct: Frank Rauscher, letter to Mary Lasker, March 18, 1974, Mary Lasker Papers, Box 118.

  “In God we trust. All others [must] have data”

  193 In science, ideology tends to corrupt: “Knowledge Dethroned,” New York Times, September 28, 1975.

  193 Orthodoxy in surgery is like orthodoxy in other departments: G. Keynes, “Carcinoma of the Breast, the Unorthodox View,” Proceedings of the Cardiff Medical Society, April 1954, 40–49.

  193 You mean I had a mastectomy for nothing?: Untitled document, 1981, Rose Kushner Papers, 1953–90, Box 43, Harvard University.

  194 “In my own surgical attack on carcinoma”: Cushman Davis Haagensen, Diseases of the Breast (New York: Saunders, 1971), 674.

  194 Halsted’s “centrifugal theory”: W. S. Halsted, “The Results of Operations for the Cure of the Cancer of Breast Performed at the Johns Hopkins Hospital from June 1889 to January 1894,” Johns Hopkins Hospital Bulletin 4 (1894): 497–555.

  194 “To some extent,” he wrote: Haagensen, Diseases of the Breast, 674.

  194 “operated on cancer of the breast solely”: D. Hayes Agnew, The Principles and Practice of Surgery, Being a Treatise on Surgical Diseases and Injuries, 2nd ed. (Philadelphia: J. B. Lippincott Company, 1889), 3: 711.

  194 “I do not despair of carcinoma being cured”: Ibid.

  195 at St. Bartholomew’s Hospital in London: G. Keynes, “The Treatment of Primary Carcinoma of the Breast with Radium,” Acta Radiologica 10 (1929): 393–401; G. Keynes, “The Place of Radium in the Treatment of Cancer of the Breast,” Annals of Surgery 106 (1937): 619–30. For biographical details, see W. LeFanu, “Sir Geoffrey Keynes (1887–1982),” Bulletin of the History of Medicine 56, no. 4 (1982): 571–73.

  195 In August 1924, Keynes examined a patient: “The Radiation Treatment of Carcinoma of the Breast,” St. Bartholomew’s Hospital Reports, vol. 60, ed. W. McAdam Eccles et al. (London: John Murray, 1927), 91–93.

  195 “The ulcer rapidly heal[ed]”: Ibid.

  195 “extension of [the] operation beyond a local removal”: Ibid., 94.

  196 the lumpectomy: Roger S. Foster Jr., “Breast Cancer Detection and Treatment: A Personal and Historical Perspective,” Archives of Surgery 138, no. 4 (2003): 397–408.

  196 George Barney Crile: Ibid.; G. Crile Jr., “The Evolution of the Treatment of Breast Cancer,” Breast Cancer: Controversies in Management, ed. L. Wise and H. Johnson Jr. (Armonk, NY: Futura Publishing Co., 1994).

  196 Crile’s father. George Crile Sr.: Narendra Nathoo, Frederick K. Lautzenheiser, and Gene H. Barnett, “The First Direct Human Blood Transfusion: the Forgotten Legacy of George W. Crile,” Neurosurgery 64 (2009): 20–26; G. W. Crile, Hemorrhage and Transfusion: An Experimental and Clinical Research (New York: D. Appleton, 1909).

  196 Political revolutions, the writer Amitav Ghosh writes: Amitav Ghosh, Dancing in Cambodia, at Large in Burma (New Delhi: Ravi Dayal, 1998), 25.

  196 Crile Jr. was beginning to have his own doubts: Foster, “Breast Cancer Detection and Treatment”; George Crile, The Way It Was: Sex, Surgery, Treasure and Travel (Kent, OH: Kent University Press, 1992), 391–400.

  197 Crile soon gave up on the radical mastectomy: George Crile Jr., “Treatment of Breast Cancer by Local Excision,” American Journal of Surgery 109 (1965): 400–403; George Crile Jr., “The Smaller the Cancer the Bigger the Operation? Rational of Small Operations for Small Tumors and Large Operations for Large Tumors,” Journal of the American Medical Association 199 (1967): 736–38; George Crile Jr., A Biologic Consideration of Treatment of Breast Cancer (Springfield, IL: Charles C. Thomas, 1967); G. Crile Jr. and S. O. Hoerr, “Results of Treatment of Carcinoma of the Breast by Local Excision,” Surgery, Gynecology, and Obstetrics 132 (1971): 780–82.

  197 two statisticians, Jerzy Neyman and Egon Pearson: J. Neyman and E. S. Pearson, “On the Use and Interpretation of Certain Test Criteria for Purposes of Statistical Inference. Part I,” Biometrika 20A, nos. 1–2 (1928): 175–240; J. Neyman and E. S. Pearson, “On the Use and Interpretation of Certain Test Criteria for Purposes of Statistical Inference. Part II,” Biometrika 20A, nos. 3–4 (1928): 263–94.

  198 “Go thou and do likewise”: Haagensen, Diseases of the Breast, 674.

  198 It took a Philadelphia surgeon: Kate Travis, “Bernard Fisher Reflects on a Half-Century’s Worth of Breast Cancer Research,” Journal of the National Cancer Institute 97, no. 22 (2005): 1636–37.

  199 “It has become apparent”: Bernard Fisher, Karnosfky Memorial Lecture transcript, Rose Kushner papers, Box 4, File 62, Harvard University.

  199 Thalidomide, prescribed widely to control: Phillip Knightley, Suffer the Children: The Story of Thalidomide (New York: Viking Press, 1979).

  199 In Texas, Jane Roe: Roe v. Wade, 410 U.S. 113 (1973).

  199 “Refuse to submit to a radical mastectomy”: “Breast Cancer: Beware of These Danger Signals,” Chicago Tribune, October 3, 1973.

  199 Rachel Carson, the author of Silent Spring: Ellen Leopold, A Darker Ribbon: Breast Cancer, Women, and Their Doctors in the Twentieth Century (Boston: Beacon Press, 1999), 199.

  200 Betty Rollin and Rose Kushner: Betty Rollin, First, You Cry (New York: Harper, 2000); Rose Kushner, Why Me? (Philadelphia: Saunders Press, 1982).

  200 “Happily for women,” Kushner wrote: Rose Kushner papers, Box 2, File 22; Kushner, Why Me?

  200 In 1967, bolstered by the activism: See Fisher’s NSABP biography at http://www .nsabp.pitt.edu/BCPT_Speakers_Biographies.asp (accessed January 11, 2010).

  200 “The clinician, no matter how venerable”: Bernard Fisher, “A Commentary on the Role of the Surgeon in Primary Breast Cancer,” Breast Cancer Research and Treatment 1 (1981): 17–26.

  200 “In God we trust”: “Treating Breast Cancer: Findings Question Need for Removal,” Washington Post, October 29, 1979.

  200 “To get a woman to participate in a clinical trial”: “Bernard Fisher in Conversation,” Pitt Med Magazine (University of Pittsburgh School of Medicine magazine), July 2002.

  200 Fisher’s NSABP mastectomy trial: Bernard Fisher et al., “Findings from NSABP Protocol No. B-04: Comparison of Radical Mastectomy with Alternative Treatments. II. The Clinical and Biological Significance of Medial-Central Breast Cancers,” Cancer 48, no. 8 (1981): 1863–72.

  “The smiling oncologist”

  202 Few doctors in this country: Rose Kushner, “Is Aggressive Adjuvant Chemotherapy the Halsted Radical of the ’80s?” CA: A Cancer Journal for Clinicians 34, no. 6 (1984): 345–51.

  202 And it is solely by risking life: Georg Wilhelm Friedrich Hegel, The Phenomenology of Mind (New York: Humanities Press, 1971), 232.

  202 “large-scale chemotherapeutic attack”: James D. Hardy, The World of Surgery, 1945–1985: Memoirs of One Participant (Philadelphia: University of Pennsylvania Press, 1986), 216.

  202 “our trench and our bunker”: Mickey Goulian, interview with author, December 2005.

  202 “Wandering about the NIH clinical center”: Stewart Alsop, Stay of Execution: A Sort of Memoir (New York: Lippincott, 1973), 218.

  203 “Although this was a cancer ward”: Kathleen R. Gilbert, ed. The Emotional Nature of Qualitative Research (Boca Raton, FL: CRC Press, 2001).

  203 “accepted roles, a predetermined outcome, constant stimuli”: Gerda Lerner, A Death of One’s Own (New York: Simon and Schuster, 1978), 71.

  203 “yellow and orange walls in the corridors”: “Can
cer Ward Nurses: Where ‘C’ Means Cheerful,” Los Angeles Times, July 25, 1975.

  203 the nurses wore uniforms with plastic yellow buttons: Alsop, Stay of Execution, 52.

  203 “Saving the individual patient”: Ibid., 84.

  204 In 1965, at Michigan State University: Barnett Rosenberg, Loretta Van Camp, and Thomas Krigas, “Inhibition of Cell Division in Escherichia coli by Electrolysis Products from a Platinum Electrode,” Nature 205, no. 4972 (1965): 698–99.

  205 John Cleland: Larry Einhorn, interview with author, November 2009; also see Cure, Winter 2004; Craig A. Almeida and Sheila A. Barry, Cancer: Basic Science and Clinical Aspects (Hoboken, NJ: Wiley-Blackwell, 2010), 259; “Survivor Milks Life for All It’s Worth,” Purdue Agriculture Connections, Spring 2006; “John Cleland Carried the Olympic Torch in 2000 When the Relay Came through Indiana,” Friends 4 Cures, http://www.friends4cures.org/cure_mag_article.shtml (accessed January 9, 2010).

  205 “I cannot remember what I said”: John Cleland, Cure, Winter 2004.

  205 By 1975, Einhorn had treated: Einhorn, interview with author, December 2009.

  205 “Walking up to that podium”: Ibid.

  205 “It was unforgettable”: Ibid. Also see “Triumph of the Cure,” Salon, July 29, 1999, http://www.salon.com/health/feature/1999/07/29/lance/index.html (accessed November 30, 2009).

  205 Margaret Edson’s play Wit: Margaret Edson, Wit (New York: Dramatists Play Service, 1999).

  205 “You may think my vocabulary”: Ibid., 28.

  206 “We want and need and seek better guidance”: Howard E. Skipper, “Cancer Chemotherapy Is Many Things: G.H.A. Clowes Memorial Lecture,” Cancer Research 31, no. 9 (1971): 1173–80.

  206 There was Taxol: Monroe E. Wall and Mansukh C. Wani, “Camptothecin and Taxol: Discovery to Clinic—Thirteenth Bruce F. Cain Memorial Award Lecture,” Cancer Research 55 (1995): 753–60; Jordan Goodman and Vivien Walsh, The Story of Taxol: Nature and Politics in the Pursuit of an Anti-Cancer Drug (Cambridge, England: Cambridge University Press, 2001).

  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. Bed
ford 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.