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

by Siddhartha Mukherjee

  Acknowledgments

  I have many people to thank. My wife, Sarah Sze, whose unfailing faith, love, and patience sustained this book. My daughters Leela and Aria, for whom this book was often a rival sibling; who fell asleep on many nights to the mechanical lullaby of my furious typing and then woke the next morning to find me typing again. My agent Sarah Chalfant, who read and annotated draft upon draft of my proposals; my editor Nan Graham, with whom I began to communicate with "mental telepathy" and whose thoughts are stitched into every page. My early readers: Nell Breyer, Amy Waldman, Neel Mukherjee, Ashok Rai, Kim Gutschow, David Seo, Robert Brustein, Prasant Atluri, Erez Kalir, Yariv Houvras, Mitzi Angel, Diana Beinart, Daniel Menaker, and many mentors and interviewees, particularly Robert Mayer, who were crucial in the development of this book. My parents, Sibeswar and Chandana Mukherjee and my sister, Ranu Bhattacharyya and her family, who found vacations and family gatherings swallowed up by an interminable manuscript and Chia-Ming and Judy Sze who provided sustenance and help during my frequent visits to Boston.

  As with any such book, this work also rests on the prior work of others: Susan Sontag's masterful and moving Illness as Metaphor, Richard Rhodes's The Making of the Atomic Bomb, Richard Rettig's Cancer Crusade, Barron Lerner's The Breast Cancer Wars, Natalie Angier's Natural Obsessions, Lewis Thomas's The Lives of a Cell, George Crile's The Way It Was, Adam Wishart's One in Three, Aleksandr Solzhenitsyn's Cancer Ward, David Rieff's devastating memoir Swimming in a Sea of Death, Robert Bazell's Her-2, Robert Weinberg's Racing to the Beginning of the Road, Harold Varmus's The Art and Politics of Science, Michael Bishop's How to Win the Nobel Prize, David Nathan's The Cancer Treatment Revolution, James Patterson's The Dread Disease, and Tony Judt's Postwar. Many archives and libraries were accessed as primary sources for the book: Mary Lasker's papers, Benno Schmidt's papers, George Papanicolaou's papers, Arthur Aufderheide's papers and specimen collection, William Halsted's papers, Rose Kushner's papers, the tobacco documents at UCSF, Evarts Graham's papers, Richard Doll's papers, Joshua Lederberg's papers, Harold Varmus's papers, the Boston Public Library, the Countway Library of Medicine, Columbia University libraries, and Sidney Farber's personal photographs and correspondence, shared by several sources, including Thomas Farber, his son. The manuscript was also read by Robert Mayer, George Canellos, Donald Berry, Emil Freireich, Al Knudson, Harold Varmus, Dennis Slamon, Brian Druker, Thomas Lynch, Charles Sawyers, Bert Vogelstein, Robert Weinberg, and Ed Gelmann, who provided corrections and alterations to the text.

  Harold Varmus, in particular, provided astonishingly detailed and insightful commentary and annotations--emblematic of the extraordinary generosity that I received from scientists, writers, and doctors.

  David Scadden and Gary Gilliland provided a fostering laboratory environment at Harvard. Ed Gelmann, Riccardo Dalla-Favera, and Cory and Michael Shen gave me a new academic "home" at Columbia University, where this book was finished. Tony Judt's Remarque Institute Forum (where I was a fellow) provided an inimitable environment for historical discussions; indeed, this book was conceived in its current form on a crystalline lake in Sweden during one such forum. Jason Rothauser, Paul Whitlatch, and Jaime Wolf read, edited, and checked the facts and figures in the manuscript. Alexandra Truitt and Jerry Marshall researched and cleared copyrights for the pictures.

  Notes

  vii Susan Sontag, Illness as Metaphor and AIDS and Its Metaphors (New York: Picador, 1990), 3.

  PROLOGUE

  1 Diseases desperate grown: William Shakespeare, Hamlet, Act IV, Scene III.

  1 Cancer begins and ends with people: June Goodfield, The Siege of Cancer (New York: Random House, 1975), 219.

  4 In Aleksandr Solzhenitsyn's novel: Aleksandr Solzhenitsyn, Cancer Ward (New York: Farrar, Straus and Giroux, 1968).

  5 Atossa, the Persian queen: Herodotus, The Histories (Oxford: Oxford University Press, 1998), 223.

  6 "The universe," the twentieth-century biologist: John Burdon Sanderson Haldane, Possible Worlds and Other Papers (New York: Harper & Brothers, 1928), 286.

  PART ONE:

  "OF BLACKE CHOLOR, WITHOUT BOYLING"

  9 In solving a problem of this sort: Arthur Conan Doyle, A Study in Scarlet (Whitefish, MT: Kessinger Publishing, 2004), 107.

  "A suppuration of blood"

  11 Physicians of the Utmost Fame: Hilaire Belloc, Cautionary Tales for Children (New York: Alfred A. Knopf, 1922), 18-19.

  11 Its palliation is a daily task: William B. Castle, "Advances in Knowledge concerning Diseases of the Blood, 1949-1950," in The 1950 Year Book of Medicine: May 1949-May 1950 (Chicago: Year Book Publishers, 1950), 313-26.

  11 In a damp: Details concerning aminopterin and its arrival in Farber's clinic are from several sources. Sidney Farber et al., "The Action of Pteroylglutamic Conjugates on Man," Science, 106, no. 2764 (1947): 619-21; S. P. Gupta, interview with author, January 2006; and S. P. Gupta, "An Indian Scientist in America: The Story of Dr. Yellapragada Subbarao," Bulletin of the Institute of Medicine (Hyderabad) 6, no. 2 (1976): 128-43; S. P. Gupta, In Quest of Panacea (New Delhi: Evelyn Publishers, 1987).

  11 Farber's specialty was pediatric pathology: John Craig, "Sidney Farber (1903-1973)," Journal of Pediatrics 128, no. 1 (1996): 160-62. Also see "Looking Back: Sidney Farber and the First Remission of Acute Pediatric Leukemia," Children's Hospital, Boston, http://www.childrenshospital.org/gallery/index.cfm?G=49&page=2 (accessed January 4, 2010); H. R. Wiedemann, "Sidney Farber (1903-1973)," European Journal of Pediatrics, 153 (1994): 223.

  12 "It gave physicians plenty to wrangle over": John Laszlo, The Cure of Childhood Leukemia: Into the Age of Miracles (New Brunswick, NJ: Rutgers University Press, 1995), 19.

  12 "diagnosed, transfused--and sent home to die": Medical World News, November 11, 1966.

  13 "He is of dark complexion": John Hughes Bennett, "Case of Hypertrophy of the Spleen and Liver in Which Death Took Place from Suppuration of the Blood," Edinburgh Medical and Surgical Journal 64 (October 1, 1845): 413-23. Also see John Hughes Bennett, Clinical Lectures on the Principles and Practice of Medicine, 3rd ed. (New York: William Wood & Company, 1866), 620.

  13 "A suppuration of blood": Bennett, "Case of Hypertrophy of the Spleen." Also see Bennett, Clinical Lectures, 896.

  13 Rudolf Virchow, independently published: Rudolf Ludwig Karl Virchow, Cellular Pathology: As Based upon Physiological and Pathological Histology, trans. Frank Chance (London: John Churchill, 1860), 169-71, 220. Also see Bennett, Clinical Lectures, 896.

  14 seeking a name for this condition: Charles J. Grant, "Weisses Blut," Radiologic Technology 73, no. 4 (2003): 373-76.

  14 in the early 1980s, another change in name: Randy Shilts, And the Band Played On (New York: St. Martin's), 171.

  14 Virchow's approach to medicine: "Virchow," British Medical Journal, 2, no. 3171 (1921): 573-74. Also see Virchow, Cellular Pathology.

  16 Bennett's earlier fantasy: William Seaman Bainbridge, The Cancer Problem (New York: Macmillan Company, 1914), 117.

  17 Michael Anton Biermer, described: Laszlo, Cure of Childhood Leukemia, 7-9, 15.

  17 From its first symptom to diagnosis to death: Biermer, "Ein Fall von Leukamie," Virchow's Archives, 1861, S. 552, cited in Suchannek, "Case of Leukaemia," 255-69.

  19 Farber completed his advanced training: Denis R. Miller, "A Tribute to Sidney Farber--the Father of Modern Chemotherapy," British Journal of Haematology 134 (2006): 4, 20-26.

  20 What is true for E. coli: This remark, attributed to Monod (perhaps apocryphally), appears several times in the history of molecular biology, although its precise origins remain unknown. See, for instance, Theresa M. Wizemann and Mary-Lou Pardue, eds., Exploring the Biological Contributions to Human Health: Does Sex Matter? (Washington, DC: National Academy Press, 2001), 32; Herbert Claus Friedmann, "From Butyribacterium to E. coli: An Essay on Unity in Biochemistry," Perspectives in Biology and Medicine 47, no. 1 (2004): 47-66.

  "A monster more insatiable than the guillotine"


  21 The medical importance of leukemia: Jonathan B. Tucker, Ellie: A Child's Fight Against Leukemia (New York: Holt, Rinehart, and Winston, 1982), 46.

  21 There were few successes in the treatment: John Laszlo, The Cure of Childhood Leukemia: Into the Age of Miracles (New Brunswick, NJ: Rutgers University Press, 1995), 162.

  21 a cornucopia of pharmaceutical discoveries: Michael B. Shimkin, "As Memory Serves--an Informal History of the National Cancer Institute, 1937-57," Journal of the National Cancer Institute 59 (suppl. 2) (1977): 559-600.

  21 the drug was reextracted: Eric Lax, The Mold in Dr. Florey's Coat: The Story of the Penicillin Miracle (New York: Henry Holt and Co., 2004), 67.

  21 In 1942, when Merck had shipped: "Milestone Moments in Merck History," http://www.merck.com/about/feature_story/01062003_penicillin.html (site is no longer available but can be accessed through http://www.archive.org/web/web.php).

  21 A decade later, penicillin: E. K. Marshall, "Historical Perspectives in Chemotherapy," Advances in Chemotherapy 13 (1974): 1-8. Also see Science News Letter 41 (1942).

  22 chloramphenicol in 1947: John Ehrlich et al., "Chloromycetin, a New Antibiotic from a Soil Actinomycete," Science 106, no. 2757 (1947): 417.

  22 tetracycline in 1948: B. M. Duggar, "Aureomycin: A Product of the Continuing Search for New Antibiotics," Annals of the New York Academy of Science 51 (1948): 177-81.

  22 "The remedies are in our own backyard": Time, November 7, 1949.

  22 In a brick building on the far corner: John F. Enders, Thomas H. Weller, and Frederick C. Robbins, "Cultivation of the Lansing Strain of Poliomyelitis Virus in Cultures of Various Human Embryonic Tissues," Science 49 (1949): 85-87; Fred S. Rosen, "Isolation of Poliovirus--John Enders and the Nobel Prize," New England Journal of Medicine 351 (2004): 1481-83.

  22 by 1950, more than half the medicines: A. N. Richards, "The Production of Penicillin in the United States: Extracts and Editorial Comment," Annals of Internal Medicine, suppl. 8 (1969): 71-73. Also see Austin Smith and Arthur Herrick, Drug Research and Development (New York: Revere Publishing Co., 1948).

  22 Typhoid fever: Anand Karnad, Intrinsic Factors: William Bosworth Castle and the Development of Hematology and Clinical Investigation at Boston City Hospital (Boston: Harvard Medical School, 1997).

  22 Even tuberculosis: Edgar Sydenstricker, "Health in the New Deal," Annals of the American Academy of Political and Social Science 176, Social Welfare in the National Recovery Program (1934): 131-37.

  22 The life expectancy of Americans: Lester Breslow, A Life in Public Health: An Insider's Retrospective (New York: Springer, 2004), 69. Also see Nicholas D. Kristof, "Access, Access, Access," New York Times, March 17, 2010.

  22 Hospitals proliferated: Rosemary Stevens, In Sickness and in Wealth (New York: Basic Books, 1989), 204, 229.

  22 As one student observed: Temple Burling, Edith Lentz, and Robert N. Wilson, The Give and Take in Hospitals (New York: Putnum, 1956), 9.

  22 Lulled by the idea of the durability: From Newsweek and Time advertisements, 1946-48. Also see Ruth P. Mack, "Trends in American Consumption," American Economic Review 46, no. 2, (1956):55-68.

  23 "illness" now ranked third: Herbert J. Gans, The Levittowners: Ways of Life and Politics in a New Suburban Community (New York: Alfred A. Knopf), 234.

  23 Fertility rose steadily: Paul S. Boyer et al., The Enduring Vision: A History of the American People (Florence, KY: Cengage Learning, 2008), 980.

  23 The "affluent society": John Kenneth Galbraith, The Affluent Society (New York: Houghton Mifflin, 1958).

  23 In May 1937: "Cancer: The Great Darkness," Fortune, May 1937.

  24 In 1899, when Roswell Park: Robert Proctor, Cancer Wars: How Politics Shapes What We Know and Don't Know About Cancer (New York: Basic Books, 1995), 20.

  24 Smallpox was on the decline: K. A. Sepkowitz, "The 1947 Smallpox Vaccination Campaign in New York City, Revisited," Emerging Infectious Diseases 10, no. 5 (2004): 960-61. Also see D. E. Hammerschmidt, "Hands: The Last Great Smallpox Outbreak in Minnesota (1924-25)," Journal of Laboratory and Clinical Medicine 142, no. 4 (2003): 278.

  24 Between 1900 and 1916: Lucius Duncan Bulkley, Cancer and Its Non-Surgical Treatment (New York: W. Wood & Co., 1921).

  24 By 1926, cancer: Proctor, Cancer Wars, 66.

  24 In May that year, Life: "U.S. Science Wars against an Unknown Enemy: Cancer," Life, March 1, 1937.

  24 When cancer appeared: "Medicine: Millions for Cancer," Time, July 5, 1937; "Medicine: After Syphilis, Cancer," Time, July 19, 1937.

  24 American Association for Cancer Research: "AACR: A Brief History," http://www.aacr.org/home/about-us/centennial/aacr-history.aspx (accessed January 4, 2010).

  25 from 70,000 men and women in 1911: "A Cancer Commission," Los Angeles Times, March 4, 1927.

  25 Neely asked Congress: 69th Cong., 2nd sess., Congressional Record, 68 (1927): p3 2922.

  25 Within a few weeks: Richard A. Rettig, Cancer Crusade: The Story of the National Cancer Act of 1971 (Lincoln, NE: Author's Choice Press, 1977), 44.

  25 In June, a joint Senate-House conference: "National Cancer Act of 1937," Office of Government and Congressional Relations, Legislative History, http://legislative.cancer.gov/history/1937 (accessed November 8, 2009).

  25 An advisory council of scientists: Shimkin, "As Memory Serves," 559-600.

  26 "The nation is marshaling its forces": Congressional Record, appendix 84:2991 (June 30, 1939); Margot J. Fromer, "How, After a Decade of Public & Private Wrangling, FDR Signed NCI into Law in 1937," Oncology Times 28 (19): 65-67.

  26 The U.S. Marine Hospital: Ora Marashino, "Administration of the National Cancer Institute Act, August 5, 1937, to June 30, 1943," Journal of the National Cancer Institute 4: 429-43.

  26 "mostly silent": Shimkin, "As Memory Serves," 599-600.

  26 "programmatic response to cancer": Ibid.

  26 "a nice quiet place out here in the country": Ibid.

  26 In the early 1950s, Fanny Rosenow: Jimmie C. Holland and Sheldon Lewis, The Human Side of Cancer (New York: Harper Collins, 2001).

  26 In 1946-47, Neely and Senator Claude Pepper: See House Foreign Affairs Committee, House Report 2565, 79th Cong., 2nd sess. Also see Report 1743 to the 79th Cong., 2nd sess., July 18, 1946; "Could a 'Manhattan Project' Conquer Cancer?" Washington Post, August 4, 1946.

  27 "Leukemia," as one physician put it: J. V. Pickstone, "Contested Cumulations: Configurations of Cancer Treatments through the Twentieth Century," Bulletin of the History of Medicine 81, no. 1 (2007): 164-96.

  27 If leukemia "belonged" anywhere: Grant Taylor, Pioneers in Pediatric Oncology (Houston: University of Texas M. D. Anderson Cancer Center, 1990).

  28 half a pound of chicken liver: George Washington Corner, George Hoyt Whipple and His Friends: The Life-Story of a Nobel Prize Pathologist (Philadelphia: Lippincott, 1963), 187.

  28 regurgitated gastric juices: Taylor, Pioneers in Pediatric Oncology, 29; George R. Minot, "Nobel Lecture: The Development of Liver Therapy in Pernicious Anemia," Nobel Lectures, Physiology or Medicine, 1922-1941 (Amsterdam: Elsevier Publishing Company, 1965).

  28 spiced up with butter, lemon, and parsley: Francis Minot Rackemann, The Inquisitive Physician: The Life and Times of George Richards Minot (Cambridge: Harvard University Press, 1956), 151.

  28 Minot and his team of researchers: George R. Minot and William P. Murphy, "Treatment of Pernicious Anemia by a Special Diet," Journal of the American Medical Association, 87 (7): 470-76.

  28 conclusively demonstrated in 1926: Minot, "Nobel Lecture."

  28 In 1934, Minot and two of his colleagues: Ibid.

  28 in the cloth mills of Bombay: Lucy Wills, "A Biographical Sketch," Journal of Nutrition 108 (1978), 1379-83.

  28 In 1928, a young English physician named Lucy Willis: H. Bastian, "Lucy Wills (1888-1964): The Life and Research of an Adventurous Independent Woman," Journal of the Royal College of Physicians of Edinburgh 38:89-91.

  28 Wills factor: Janet Watson and William B.
Castle, "Nutritional Macrocytic Anemia, Especially in Pregnancy: Response to a Substance in Liver Other Than That Effective in Pernicious Anemia," American Journal of the Medical Sciences 211, no. 5 (1946): 513-30; Lucy Wills, "Treatment of 'Pernicious Anaemia' of Pregnancy and 'Tropical Anaemia,' with Special Reference to Yeast Extract as a Curative Agent," British Medical Journal 1, no. 3676 (1931): 1059-64.

  29 He called this phenomenon acceleration: Sidney Farber et al., "The Action of Pteroylglutamic Conjugates on Man," Science 106, no. 2764 (1947): 619-21. Also see Mills et al., "Observations on Acute Leukemia in Children Treated with 4-Aminopteroylglutamic Acid," Pediatrics 5, no. 1 (1950): 52-56.

  30 In his long walks from his laboratory: Thomas Farber, interview with author, November 2007.

  30 He had arrived in Boston in 1923: S. P. Gupta, "An Indian Scientist in America: The Story of Dr. Yellapragada Subbarao," Bulletin of the Institute of Medicine (Hyderabad), 6, no. 2 (1976): 128-43.

  31 In the 1920s, another drug company: Corner, George Hoyt Whipple, 188.

  31 But in 1946, after many failed attempts: Gupta, "Indian Scientist in America."

  Farber's Gauntlet

  32 Throughout the centuries: William Seaman Bainbridge, The Cancer Problem (New York: Macmillan Company, 1914), 2.

  32 The search for a way to eradicate this scourge: "Cancer Ignored," Washington Post, August 5, 1946.

  33 Robert Sandler: Biographical details were taken from an article in the Boston Herald, April 9, 1948, referred to in S. P. Gupta, "An Indian Scientist in America: The Story of Dr. Yellapragada Subbarao," Bulletin of the Institute of Medicine (Hyderabad), 6, no. 2 (1976): 128-43; and S. P. Gupta, interview with author, January 2006. Sandler's address in Dorchester and his father's profession are from the Boston directory for 1946, obtained from the Boston Public Library. Sandler's case (R.S.) is described in detail in Sidney Farber's paper below.

  33 Farber's treatment of Robert Sandler: Sidney Farber, "Temporary Remissions in Acute Leukemia in Children Produced by Folic Acid Antagonist, 4-Aminopteroyl-Glutamic Acid (Aminopterin)," New England Journal of Medicine 238 (1948): 787-93.