The Emperor of All Maladies

by Siddhartha Mukherjee

  264 Entitled the Federal Cigarette Labeling and Advertising Act: Cigarette Labeling and Advertising Act, Title 15, chap. 36, 1965; “Quiet Victory of the Cigarette Lobby.”

  265 In the early summer of 1967, Banzhaf: John F. Banzhaf III v. Federal Communications Commission et al., 405 F.2d 1082 (D.C. Cir. 1968).

  266 “The advertisements in question”: Ibid.

  266 “a squadron of the best-paid lawyers in the country”: John Banzhaf, interview with author, June 2008.

  266 “Doubt is our product”: “Smoking and Health Proposal,” 1969, Brown & Williamson Collection, Legacy Tobacco Documents Library, University of California, San Francisco.

  266 In 1968, a worn and skeletal-looking William Talman: A video of the ad is available at http://www.classictvads.com/smoke_1.shtml (accessed December 26, 2009).

  267 The last cigarette commercial: See Brandt, Cigarette Century, 271.

  267 He had already died: “William Hopper, Actor, Dies; Detective in ‘Perry Mason,’ 54,” New York Times, March 7, 1970.

  267 cigarette consumption in America plateaued: U.S. Department of Agriculture, Tobacco Situation and Outlook Report, publication no. TBS-226 (Washington, DC: U.S. Department of Agriculture, Economic Research Service, Commodity Economics Division, April 1994) table 2; G. A. Glovino, “Surveillance for Selected Tobacco-Use Behaviors—United States, 1900–1994,” Morbidity and Mortality Weekly Report CDC Surveillance Summaries 43, no. 3 (1994): 1–43.

  267 “Statistics,” the journalist Paul Brodeur once wrote: Paul Brodeur, Outrageous Misconduct: The Asbestos Industry on Trial (New York: Pantheon Books, 1985).

  267 She represented the midpoint: See “Women and Smoking,” Report of the U.S. Surgeon General 2001, and prior report from 1980.

  268 “[It’s] a game only for steady nerves”: See, for example, Popular Mechanics, November 1942, back cover.

  268 “never twittery, nervous or jittery”: Redd Evans and John Jacob Loeb, “Rosie the Riveter” (New York: Paramount Music Corp., 1942).

  269 Marc Edell, a New Jersey attorney: For details of Cipollone’s case see Cipollone v. Liggett Group, Inc., 505 U.S. 504 (1992).

  269 “deaf, dumb and blind”: Ibid.

  269 In the three decades between 1954 and 1984: Burson Marsteller (PR firm), Position Paper, History of Tobacco Litigation Third Draft, May 10, 1988.

  270 “Plaintiff attorneys can read the writing”: Burson Marsteller (PR firm), internal document, Cipollone postverdict communication plan, January 1, 1988.

  270 In one letter, Fred Panzer: David Michaels, Doubt Is Their Product: How Industry’s Assault on Science Threatens Your Health (Oxford: Oxford University Press, 2008), 11. Also see Brown and Williamson (B & W), “Smoking and Health Proposal,” B & W document no. 680561778-1786, 1969, available at http://legacy.library.ucsf.edu/tid/nvs40f00.

  270 “In a sense, the tobacco industry may be thought”: “Research Planning Memorandum on the Nature of the Tobacco Business and the Crucial Role of Nicotine Therein,” April 14, 1972, Anne Landman’s Collection, Tobacco Documents Online, http://tobaccodocuments.org/landman/501877121–7129.html (accessed December 26, 2009).

  271 “Think of the cigarette pack as a storage container”: “Motives and Incentives in Cigarette Smoking,” 1972, Anne Landman’s Collection, Tobacco Documents Online, http://tobaccodocuments.org/landman/2024273959–3975.html (accessed December 26, 2009).

  271 Edell quizzed Liggett’s president: Cipollone v. Liggett Group, Inc., et al., transcript of proceedings [excerpt], Tobacco Products Litigation Reporter 3, no. 3 (1988): 3.2261–3.268.

  271 the Cipollone cancer trial appeared before the court in 1987: See Cipollone v. Liggett Group, Inc., et al., 893 F.2d 541 (1990); Cipollone v. Liggett Group, Inc., et al., 505 U.S. 504 (1992).

  272 By 1994, the per capita consumption of cigarettes in America: “Trends in Tobacco Use,” American Lung Association Research and Program Services Epidemiology and Statistics Unit, July 2008, http://www.lungusa.org/finding-cures/for-professionals/epidemiology-and-statistics-rpts.html (accessed December 27, 2009).

  272 Among men, the age-adjusted incidence: “Trends in Lung Cancer Morbidity and Mortality,” American Lung Association Epidemiology and Statistics Unit, Research and Program Services Division, September 2008, http://www.lungusa.org/finding-cures/for-professionals/epidemiology-and-statistics-rpts.html (accessed December 27, 2009).

  272 In 1994, in yet another landmark case: “Mississippi Seeks Damages from Tobacco Companies,” New York Times, May 24, 1994.

  272 “You caused the health crisis”: Ibid.

  273 Several other states then followed: “Tobacco Settlement Nets Florida $11.3B,” USA Today, August 25, 1997; “Texas Tobacco Deal Is Approved,” New York Times, January 17, 1998.

  273 In June 1997, facing a barrage: The Master Settlement Agreement is available online from the Office of the Attorney General of California, http://www.ag.ca.gov/tobacco/msa.php (accessed December 27, 2009).

  273 Tobacco smoking is now a major preventable cause: Gu et al., “Mortality Attributable to Smoking in China,” New England Journal of Medicine 360, no. 2 (2009): 150–59; P. Jha et al., “A Nationally Representative Case-Control Study of Smoking and Death in India,” New England Journal of Medicine 358, no. 11 (2008): 1137–47.

  273 Richard Peto, an epidemiologist at Oxford: Ibid.

  274 In China, lung cancer is already: Gu et al., “Mortality Attributable to Smoking in China.”

  274 In 2004, tobacco companies signed: Samet et al., “Mexico and the Tobacco Industry,” BMJ 3 (2006): 353–55.

  274 In the early 1990s, a study noted, British American Tobacco: Gilmore et al., “American Tobacco’s Erosion of Health Legislation in Uzbekistan,” BMJ 332 (2006): 355–58.

  274 Cigarette smoking grew by about 8 percent: Ibid.

  274 In a recent editorial in the British Medical Journal: Ernesto Sebrié and Stanton A. Glantz, “The Tobacco Industry in Developing Countries,” British Medical Journal 332, no. 7537 (2006): 313–14.

  “Curiouser and curiouser”

  276 You’re under a lot of stress: Transcript of interview with Barry Marshall and an anonymous interviewer, National Health and Medical Research Council archives, Australia.

  276 In the early 1970s, for instance, a series of studies: J. S. Harrington, “Asbestos and Mesothelioma in Man,” Nature 232, no. 5305 (1971): 54–55; P. Enterline, P. DeCoufle, and V. Henderson, “Mortality in Relation to Occupational Exposure in the Asbestos Industry,” Journal of Occupational Medicine 14, no. 12 (1972): 897–903; “Asbestos, the Saver of Lives, Has a Deadly Side,” New York Times, January 21, 1973; “New Rules Urged For Asbestos Risk,” New York Times, October 5, 1975.

  277 In 1971, yet another such study identified: Arthur L. Herbst, Howard Ulfelder, and David C. Poskanzer, New England Journal of Medicine 284, no. 15 (1971): 878–81.

  277 In the late 1960s, a bacteriologist named Bruce Ames: Bruce N. Ames et al., “Carcinogens Are Mutagens: A Simple Test System Combining Liver Homogenates for Activation and Bacteria for Detection,” Proceedings of the National Academy of Sciences of the United States of America 70, no. 8 (1973): 2281–85; Bruce N. Ames, “An Improved Bacterial Test System for the Detection and Classification of Mutagens and Carcinogens,” Proceedings of the National Academy of Sciences of the United States of America 70, no. 3 (1973): 82–786.

  278 So did X-rays, benzene compounds, and nitrosoguanidine: “Carcinogens as Frameshift Mutagens: Metabolites and Derivatives of 2-Acetylaminofluorene and Other Aromatic Amine Carcinogens,” Proceedings of the National Academy of Sciences of the United States of America 69, no. 11 (1972): 3128–32.

  278 Not every known carcinogen scored on the test: For DES, see Ishikawa et al., “Lack of Mutagenicity of Diethylstilbestrol Metabolite and Analog, (±)-Indenestrols A and B, in Bacterial Assays,” Mutation Research/Genetic Toxicology 368, nos. 3–4 (1996): 261–65; for asbestos, see K. Szyba and A. Lange, “Presentation of Benzo(a)pyrene to Microsomal Enzymes by Asb
estos Fibers in the Salmonella/Mammalian Microsome Mutagenicity Test,” Environmental Health Perspectives 51 (1983): 337–41.

  278 A biochemistry student at Oxford: Marc A. Shampo and Robert A. Kyle, “Baruch Blumberg—Work on Hepatitis B Virus,” Mayo Clinic Proceedings 78, no. 9 (2003): 1186.

  279 The work of Baruch Blumberg: Baruch S. Blumberg, “Australia Antigen and the Biology of Hepatitis B,” Science 197, no. 4298 (1977): 17–25; Rolf Zetterstöm, “Nobel Prize to Baruch Blumberg for the Discovery of the Aetiology of Hepatitis B,” Acta Paediatrica 97, no. 3 (2008): 384–87; Shampo and Kyle, “Baruch Blumberg,” 1186.

  279 Blumberg began to scour far-flung places: A. C. Allison et al., “Haptoglobin Types in British, Spanish, Basque and Nigerian African Populations,” Nature 181 (1958): 824–25.

  279 In 1964, after a brief tenure at the NIH: Zetterstöm, “Nobel Prize to Baruch Blumberg.”

  279 One blood antigen that intrigued him: Baruch S. Blumberg, Harvey J. Alter, and Sam Visnich, “A ‘New’ Antigen in Leukemia Sera,” Journal of the American Medical Association 191, no. 7 (1965): 541–46.

  279 In 1966, Blumberg’s lab set out to characterize: Baruch S. Blumberg et al., “A Serum Antigen (Australia Antigen) in Down’s Syndrome, Leukemia, and Hepatitis,” Annals of Internal Medicine 66, no. 5 (1967): 924–31.

  279 Au and hepatitis: Blumberg, “Australia Antigen and the Biology of Hepatitis B.”

  280 “roughly circular . . . about forty-two nanometers”: Baruch Blumberg, Hepatitis B: The Hunt for a Killer Virus (Princeton: Princeton University Press, 2002), 115.

  280 By 1969, Japanese researchers: Baruch S. Blumberg, “Australia Antigen and the Biology of Hepatitis B.”; K. Okochi and S. Murakami, “Observations on Australia Antigen in Japanese,” Vox Sanguinis 15, no. 5 (1968): 374–85.

  280 But another illness soon stood out: Blumberg, Hepatitis B, 155.

  281 “discipline-determined rigidity of the constituent institutes”: Ibid., 72.

  281 By 1979, his group had devised one: Ibid., 134–46.

  282 “Since the early days of medical bacteriology”: J. Robin Warren, “Helicobacter: The Ease and Difficulty of a New Discovery (Nobel Lecture),” ChemMedChem 1, no. 7 (2006): 672–85.

  282 Barry Marshall and Robin Warren’s discovery of ulcer-causing bacteria: J. R. Warren, “Unidentified Curved Bacteria on Gastric Epithelium in Active Chronic Gastritis,” Lancet 321, no. 8336 (1983): 1273–75; Barry J. Marshall and J. Robin Warren, “Unidentified Curved Bacilli in the Stomach of Patients with Gastritis and Peptic Ulceration,” Lancet 323, no. 8390 (1984): 1311–15; Barry Marshall, Helicobacter Pioneers: Firsthand Accounts from the Scientists Who Discovered Helicobacters, 1892–1982 (Hoboken, NJ: Wiley-Blackwell, 2002); Warren, “Helicobacter: The Ease and Difficulty”; Barry J. Marshall, “Heliobacter Connections,” ChemMedChem 1, no. 8 (2006): 783–802.

  283 “On the morning of the experiment”: Marshall, “Heliobacter Connections.”

  284 The effect of antibiotic therapy on cancer: Johannes G. Kusters, Arnoud H. M. van Vliet, and Ernst J. Kuipers, “Pathogenesis of Helicobacter pylori Infection,” Clinical Microbiology Reviews 19, no. 3 (2006): 449–90.

  “A spider’s web”

  286 It is to earlier diagnosis that we must look: J. P. Lockhart-Mummery, “Two Hundred Cases of Cancer of the Rectum Treated by Perineal Excision,” British Journal of Surgery 14 (1926–27): 110–24.

  286 The greatest need we have today: Sidney Farber, letter to Etta Rosensohn, November 1962.

  286 Lady, have you been “Paptized”?: “Lady, Have You Been ‘Paptized’?” New York Amsterdam News, April 13, 1957.

  286 George Papanicolaou: For an overview, see George A. Vilos, “After Office Hours: The History of the Papanicolaou Smear and the Odyssey of George and Andromache Papanicolaou,” Obstetrics and Gynecology 91, no. 3 (1998): 479–83; S. Zachariadou-Veneti, “A Tribute to George Papanicolaou (1883–1962),” Cytopathology 11, no. 3 (2000): 152–57.

  287 By the late 1920s: Zachariadou-Veneti, “Tribute to George Papanicolaou.”

  287 As one gynecologist archly remarked: Edgar Allen, “Abstract of Discussion on Ovarian Follicle Hormone,” Journal of the American Medical Association 85 (1925): 405.

  287 Papanicolaou thus began to venture: George N. Papanicolaou, “The Cancer-Diagnostic Potential of Uterine Exfoliative Cytology,” CA: A Cancer Journal for Clinicians 7 (1957): 124–35.

  288 “aberrant and bizarre forms”: Ibid.

  288 Papanicolaou published his method: G. N. Papanicolaou, “New Cancer Diagnosis,” Proceedings of the Third Race Betterment Conference (1928): 528.

  288 “I think this work will be carried”: Ibid.

  288 Between 1928 and 1950: George A. Vilos, “After Office Hours,” Obstetrics and Gynecology 91 (March 1998): 3.

  288 A Japanese fish and bird painter: George N. Papanicolaou, “The Cell Smear Method of Diagnosing Cancer,” American Journal of Public Health and the Nation’s Health 38, no. 2 (1948): 202–5.

  289 At a Christmas party in the winter of 1950: Irena Koprowska, A Woman Wanders through Life and Science (Albany: State University of New York Press, 1997), 167–68.

  289 “It was a revelation”: Ibid.

  289 In 1952, Papanicolaou convinced the National Cancer Institute: Cyrus C. Erickson, “Exfoliative Cytology in Mass Screening for Uterine Cancer: Memphis and Shelby County, Tennessee,” CA: A Cancer Journal for Clinicians 5 (1955): 63–64.

  289 In the initial cohort of about 150,000: Harold Speert, “Memorable Medical Mentors: VI. Thomas S. Cullen (1868–1953),” Obstetrical and Gynecological Survey 59, no. 8 (2004): 557–63.

  289 557 women were found to have preinvasive cancers: Ibid.

  290 In 1913, a Berlin surgeon named Albert Salomon: D. J. Dronkers et al., eds., The Practice of Mammography: Pathology, Technique, Interpretation, Adjunct Modalities (New York: Thieme, 2001), 256.

  291 “trabeculae as thin as a spider’s web”: H. J. Burhenne, J. E. Youker, and R. H. Gold, eds., Mammography (symposium given on August 24, 1968, at the University of California School of Medicine, San Francisco) (New York: S. Karger, 1969), 109.

  294 In the winter of 1963, three men set out: Sam Shapiro, Philip Strax, and Louis Venet, “Evaluation of Periodic Breast Cancer Screening with Mammography: Methodology and Early Observations,” Journal of the American Medical Association 195, no. 9 (1966): 731–38.

  294 By the mid-1950s, a triad of forces: Thomas A. Hirschl and Tim B. Heaton, eds., New York State in the 21st Century (Santa Barbara, CA: Greenwood Publishing Group, 1999), 144.

  294 By the early 1960s, the plan had enrolled: See, for instance, Philip Strax, “Screening for breast cancer,” Clinical Obstetrics and Gynecology 20, no. 4 (1977): 781–802.

  295 Strax and Venet eventually outfitted a mobile van: Philip Strax, “Female Cancer Detection Mobile Unit,” Preventive Medicine 1, no. 3 (1972): 422–25.

  295 “Interview . . . 5 stations X 12 women”: Abraham Schiff quoted in Philip Strax, Control of Breast Cancer through Mass Screening (Philadelphia: Mosby, 1979), 148.

  296 In 1971, eight years after the study: S. Shapiro et al., “Proceedings: Changes in 5-Year Breast Cancer Mortality in a Breast Cancer Screening Program,” Proceedings of the National Cancer Conference 7 (1972): 663–78.

  296 “The radiologist,” he wrote: Philip Strax, “Radiologist’s Role in Screening Mammography,” unpublished document quoted in Barron H. Lerner, “‘To See Today with the Eyes of Tomorrow’: A History of Screening Mammography,” Canadian Bulletin of Medical History 20, no. 2 (2003): 299–321.

  296 “Within 5 years, mammography has moved”: G. Melvin Stevens and John F. Weigen, “Mammography Survey for Breast Cancer Detection. A 2-Year Study of 1,223 Clinically Negative Asymptomatic Women over 40,” Cancer 19, no. 1 (2006): 51–59.

  296 “The time has come”: Arthur I. Holleb, “Toward Better Control of Breast Cancer,” American Cancer Society press release, October 4, 1971 (New York: ACS Media Division), Folde
r: Breast Cancer Facts, quoted in Lerner, “‘To See Today with the Eyes of Tomorrow.’”

  296 the Breast Cancer Detection and Demonstration Project: Myles P. Cunningham, “The Breast Cancer Detection Demonstration Project 25 Years Later,” CA: A Cancer Journal for Clinicians 47, no. 3 (1997): 131–33.

  298 Between 1976 and 1992, enormous parallel trials: See below for particular studies. Also see Madelon Finkel, ed., Understanding the Mammography Controversy (Westport, CT: Praeger, 2005), 101–5.

  298 In Canada, meanwhile, researchers lurched: A. B. Miller, G. R. Howe, and C. Wall, “The National Study of Breast Cancer Screening Protocol for a Canadian Randomized Controlled Trial of Screening for Breast Cancer in Women,” Clinical Investigative Medicine 4, nos. 3–4 (1981): 227–58.

  298 Edinburgh was a disaster: A. Huggins et al., “Edinburgh Trial of Screening for Breast Cancer: Mortality at Seven Years,” Lancet 335, no. 8684 (1990): 241–46; Denise Donovan et al., “Edinburgh Trial of Screening for Breast Cancer,” Lancet 335, no. 8695 (1990): 968–69.

  298 The Canadian trial, meanwhile: Miller, Howe, and Wall, “National Study of Breast Cancer Screening Protocol.”

  298 For a critical evaluation of the CNBSS, HIP, and Swedish studies, see David Freedman et al., “On the Efficacy of Screening for Breast Cancer,” International Journal of Epidemiology 33, no. 1 (2004): 43–5.

  298 Randomization problems in the Canadian National Breast Screening Study: Curtis J. Mettlin and Charles R. Smart, “The Canadian National Breast Screening Study: An Appraisal and Implications for Early Detection Policy,” Cancer 72, no. S4 (1993): 1461–65; John C. Bailar III and Brian MacMahon, “Randomization in the Canadian National Breast Screening Study: A Review for Evidence of Subversion,” Canadian Medical Association Journal 156, no. 2 (1997): 193–99.

  299 “Suspicion, like beauty”: Cornelia Baines, Canadian Medical Association Journal 157 (August 1, 1997): 249.

  299 “One lesson is clear”: Norman F. Boyd, “The Review of Randomization in the Canadian National Breast Screening Study: Is the Debate Over?” Canadian Medical Association Journal 156, no. 2 (1997): 207–9.