329 "There you are, the future patient": Ibid., 9.
330 In May 1997, exactly eleven years after: John C. Bailar and Heather L. Gornik, "Cancer Undefeated," New England Journal of Medicine 336, no. 22 (1997): 1569-74.
332 Pressed on public television, he begrudgingly conceded: "Treatment vs. Prevention," NewsHour with Jim Lehrer, May 29, 1997, PBS, transcript available at http://www.pbs .org/newshour/bb/health/may97/cancer_5-29.html (accessed January 2, 2010).
332 "'Cancer' is, in truth, a variety of diseases": Barnett S. Kramer and Richard D. Klausner, "Grappling with Cancer--Defeatism versus the Reality of Progress," New England Journal of Medicine 337, no. 13 (1997): 931-35.
PART FIVE:
"A DISTORTED VERSION OF OUR NORMAL SELVES"
335 It is vain to speak of cures: Robert Burton, The Anatomy of Melancholy (: C. Armstrong and Son, 1893), 235.
335 You can't do experiments to see: Samuel S. Epstein, Cancer-Gate: How to Win the Losing Cancer War (Amityville, NY: Baywood Publishing Company, 2005), 57.
335 What can be the "why" of these happenings?: Peyton Rous, "The Challenge to Man of the Neoplastic Cell," Nobel Lectures, Physiology or Medicine, 1963-1970 (Amsterdam: Elsevier Publishing Company, 1972).
"A unitary cause"
340 As early as 1858: Rudolf Virchow, Lecture XX, Cellular Pathology as Based upon Physiological and Pathological Histology, trans. Frank Chance (London: Churchill, 1860). The passage on irritation appears on page 488 of the translated version: "A pathological tumor in man forms . . . where any pathological irritation occurs . . . all of them depend upon a proliferation of cells."
340 Walther Flemming, a biologist working in Prague: Neidhard Paweletz, "Walther Flemming: Pioneer of Mitosis Research," Nature Reviews Molecular Cell Biology 2 (2001): 72-75.
340 It was Virchow's former assistant David Paul von Hansemann: Leon P. Bignold, Brian L. D. Coghlan, and Hubertus P. A. Jersmann, eds., Contributions to Oncology: Context, Comments and Translations (Basel: Birkhauser Verlag, 2007), 83-90.
341 Boveri devised a highly unnatural experiment: Theodor Boveri, Concerning the Origin of Malignant Tumours by Theodor Boveri, translated and annotated by Henry Harris (New York: Cold Spring Harbor Press, 2006). This is a reprint and new translation of the original text.
342 "unitary cause of carcinoma": Ibid., 56.
342 not "an unnatural group of different maladies": Ibid., 56.
342 In 1910, four years before Boveri had published his theory: Peyton Rous, "A Transmissible Avian Neoplasm (Sarcoma of the Common Fowl)," Journal of Experimental Medicine 12, no. 5 (1910): 696-705; Peyton Rous, "A Sarcoma of the Fowl Transmissible by an Agent Separable from the Tumor Cells," Journal of Experimental Medicine 13, no. 4 (1911): 397-411.
342 In 1909, a year before: Karl Landsteiner et al., "La transmission de la paralysie infantile aux singes," Compt. Rend. Soc. Biologie 67 (1909).
343 In the early 1860s, working alone: Gregor Mendel, "Versuche uber Plfanzenhybriden," Verhandlungen des Naturforschenden Vereines in Brunn. IV fur das Jahr 1865, Abhandlungen (1866): 3-47. English translation available at http://www.esp.org/foundations/genetics/classical/gm-65.pdf (accessed January 2, 2010). Also see Robin Marantz Henig, The Monk in the Garden: The Lost and Found Genius of Gregor Mendel, the Father of Genetics (Boston: Mariner Books, 2001), 142.
343 decades later, in 1909, botanists: Wilhelm Ludwig Johannsen, Elemente der Exakten Erblichkeitlehre (1913), http://caliban.mpiz-koeln.mpg.de/johannsen/elemente/index.html (accessed January 2, 2010).
344 In 1910, Thomas Hunt Morgan: See T. H. Morgan, "Chromosomes and Heredity," American Naturalist 44 (1910): 449-96. Also see Muriel Lederman, "Research Note: Genes on Chromosomes: the Conversion of Thomas Hunt Morgan," Journal of the History of Biology 22, no. 1 (1989): 163-76.
344 The third vision of the "gene": Oswald T. Avery et al., "Studies on the Chemical Nature of the Substance Inducing Transformation of Pneumococcal Types: Induction of Transformation by a Deoxyribonucleic Acid Fraction Isolated from Pneumococcus Type III," Journal of Experimental Medicine 79 (1944): 137-58.
345 George Beadle, Thomas Morgan's student: See George Beadle, "Genes and Chemical Reactions in Neurospora," Nobel Lectures, Physiology or Medicine, 1942-1962 (Amsterdam: Elsevier Publishing Company, 1964), 587-99.
346 In the mid-1950s, biologists termed: See for instance Francis Crick, "Ideas on Protein Synthesis," October 1956, Francis Crick Papers, National Library of Medicine. Crick's statement of the central dogma proposed that RNA could be back converted as a special case, but that proteins could never be back converted into DNA or RNA. Reverse transcription was thus left as a possibility.
347 In 1872, Hilario de Gouvea: A. N. Monteiro and R. Waizbort, "The Accidental Cancer Geneticist: Hilario de Gouvea and Hereditary Retinoblastoma," Cancer Biology and Therapy 6, no. 5 (2007): 811-13.
348 In 1928, Hermann Joseph Muller: See Hermann Muller, "The Production of Mutations," Nobel Lectures, Physiology or Medicine, 1942-1962 (Amsterdam: Elsevier Publishing Company, 1964).
348 "the doctor may then want to call in his geneticist friends for consultation!": Thomas Morgan, "The Relation of Genetics to Physiology and Medicine," Nobel Lectures, Physiology or Medicine 1922-1941 (Amsterdam: Elsevier Publishing Company, 1965).
Under the Lamps of Viruses
349 Unidentified flying objects, abominable snowmen: Medical World News, January 11, 1974.
349 The biochemist Arthur Kornberg once joked: Arthur Kornberg, "Ten Commandments: Lessons from the Enzymology of DNA Replication," Journal of Bacteriology 182, no. 13 (2000): 3613-18.
351 Temin was cooking up an unusual experiment: See Howard Temin and Harry Rubin, "Characteristics of an Assay for Rous Sarcoma Virus," Virology 6 (1958): 669-83.
351 "The virus, in some structural as well as functional sense": Howard Temin, quoted in Howard M. Temin et al., The DNA Provirus: Howard Temin's Scientific Legacy (Washington, DC: ASM Press, 1995), xviii.
352 "Temin had an inkling": J. Michael Bishop, interview with author, August 2009.
352 "The hypothesis": J. Michael Bishop in Temin et al., DNA Provirus, 81.
353 Mizutani was a catastrophe: See Robert Weinberg, Racing to the Beginning of the Road (New York: Bantam, 1997), 61.
353 At MIT, in Boston: Ibid., 61-65.
353 "It was all very dry biochemistry": Ibid., 64.
354 In their respective papers: David Baltimore, "RNA-Dependent DNA Polymerase in Virions of RNA Tumor Viruses," Nature 226, no. 5252 (1970): 1209-11; and H. M Temin and S. Mizutani, "RNA-Dependent DNA Polymerase in Virions of Rous Sarcoma Virus," Nature 226, no. 5252 (1970): 1211-13.
355 Spiegelman raced off to prove: Weinberg, Racing to the Beginning, 70.
355 "It became his single-minded preoccupation": Robert Weinberg, interview with author, January 2009.
356 "The hoped-for human virus": Weinberg, Racing to the Beginning, 83.
"The hunting of the sarc"
357 For the Snark was a Boojum, you see: Lewis Carroll, The Hunting of the Snark: An Agony in Eight Fits (New York: Macmillan, 1914), 53.
358 By analyzing the genes altered in these mutant viruses: For a review of Duesberg's and Vogt's contributions, see G. Steven Martin, "The Hunting of the Src," Nature Reviews Molecular Cell Biology 2, no. 6 (2001): 467-75.
358 A chance discovery in Ray Erikson's laboratory: J. S. Brugge and R. L. Erikson, "Identification of a Transformation-Specific Antigen Induced by an Avian Sarcoma Virus," Nature 269, no. 5626 (1977): 346-48.
360 other scientists nicknamed the project: See, for instance, Martin, "The Hunting of the Src."
361 "Src," Varmus wrote in a letter: Harold Varmus to Dominique Stehelin, February 3, 1976, Harold Varmus papers, National Library of Medicine archives. Also see Stehelin et al., "DNA Related to the Transforming Genes of Avian Sarcoma Viruses Is Present in Normal DNA," Nature 260, no. 5547 (March 1976): 170-73.
362 "Nature," Rous wrote in 1966: Peyton Rous, "The Challenge to Man of the Neoplastic Ce
ll," Nobel Lectures, Physiology or Medicine, 1963-1970 (Amsterdam: Elsevier Publishing Company, 1972).
363 "We have not slain our enemy": Harold Varmus, "Retroviruses and Oncogenes I," Nobel Lectures, Physiology or Medicine, 1981-1990, ed. Jan Lindsten (Singapore: World Scientific Publishing Co., 1993).
The Wind in the Trees
364 The fine, fine wind: D. H. Lawrence, "The Song of a Man Who Has Come Through," Penguin Book of First World War Poetry, ed. John Silkin (New York: Penguin Classics, 1996), 213.
365 Rowley's specialty was studying: Janet Rowley, "Chromosomes in Leukemia and Lymphoma," Seminars in Hematology 15, no. 3 (1978): 301-19.
365 In the late 1950s, Peter Nowell: P. C. Nowell and D. Hungerford, Science 142 (1960): 1497.
366 In 1969, Knudson moved: Al Knudson, interview with author, July 2009.
367 "The number two," he recalled: Ibid.
368 Knudson's two-hit theory: A. Knudson, "Mutation and Cancer: Statistical Study of Retinoblastoma," Proceedings of the National Academy of Sciences of the United States of America 68, no. 4 (1971): 820-23.
368 "Two classes of genes are apparently critical": A. Knudson, "The Genetics of Childhood Cancer," Bulletin du Cancer 75, no. 1 (1988): 135-38.
369 "jammed accelerators" and "missing brakes": J. Michael Bishop, in Howard M. Temin et al., The DNA Provirus: Howard Temin's Scientific Legacy (Washington, DC: ASM Press, 1995), 89.
A Risky Prediction
370 They see only their: Plato, The Republic of Plato, Benjamin Jowett, trans. (Oxford: Clarendon Press, 1908), 220.
370 "Isolating such a gene": Robert Weinberg, interview with author, January 2009.
371 "The chair of the department": Ibid.
371 Clarity came to him one morning: Ibid.
373 In the summer of 1979, Chiaho Shih: Ibid.
374 "If we were going to trap a real oncogene": Ibid. Also, Cliff Tabin, interview with author, December 2009.
374 In 1982, Weinberg: C. Shih and R. A. Weinberg (1982), "Isolation of a Transforming Sequence from a Human Bladder Carcinoma Cell Line," Cell 29: 161-169. Also see M. Goldfarb, K. Shimizu, M. Perucho, and M. Wigler, "Isolation and Preliminary Characterization of a Human Transforming Gene from T24 Bladder Carcinoma Cells," Nature 296 (1982): 404-9. Also see S. Pulciani et al., "Oncogenes in Human Tumor Cell Lines: Molecular Cloning of a Transforming Gene from Human Bladder Carcinoma Cells," Proceedings of the National Academy of Sciences. USA 79: 2845-49.
375 "Once we had cloned": Robert Weinberg, Racing to the Beginning of the Road (New York: Bantam, 1997), 165.
375 Ray Erikson traveled to Washington: Ray Erikson, interview with author, October 2009.
375 "I don't remember any enthusiasm": Ibid.
376 "How can one capture genes": Robert Weinberg, One Renegade Cell (New York: Basic Books, 1999), 74.
376 "We knew where Rb lived": Weinberg, interview with author.
377 Dryja began his hunt for Rb: Thaddeus Dryja, interview with author, November 2008.
378 "I stored the tumors obsessively": Ibid.
378 "It was at that moment": Ibid.
380 "We have isolated [a human gene]": Stephen H. Friend et al., "A Human DNA Segment with Properties of the Gene that Predisposes to Retinoblastoma and Osteosarcoma," Nature 323, no. 6089 (1986): 643-46.
380 When scientists tested the gene isolated by Dryja: D. W. Yandell et al., "Oncogenic Point Mutations in the Human Retinoblastoma Gene: Their Application to Genetic Counseling," New England Journal of Medicine 321, no. 25 (1989): 1689-95.
380 Its chief function is to bind to several other proteins: See for instance James A. DeCaprio, "How the Rb Tumor Suppressor Structure and Function was Revealed by the Study of Adenovirus and SV40," Virology 384, no. 2 (2009): 274-84.
380 a horde of other oncogenes and anti-oncogenes: George Klein, "The Approaching Era of the Tumor Suppressor Genes," Science 238, no. 4833 (1987): 1539-45.
382 Philip Leder's team at Harvard engineered: Timothy A. Stewart, Paul K. Pattengale, and Philip Leder, "Spontaneous Mammary Adenocarcinomas in Transgenic Mice That Carry and Express MTV/myc Fusion Genes," Cell 38 (1984): 627-37.
382 In 1988, he successfully applied for a patent: Daniel J. Kevles, "Of Mice & Money: The Story of the World's First Animal Patent," Daedalus 131, no. 2 (2002): 78.
382 "The active myc gene does not appear to be sufficient": Stewart, Pattengale, and Leder, "Spontaneous Mammary Adenocarcinomas," 627-37.
383 Leder created a second OncoMouse: E. Sinn et al., "Coexpression of MMTV/v-Ha-ras and MMTV/c-myc Genes in Transgenic Mice: Synergistic Action of Oncogenes in Vivo," Cell 49, no. 4 (1987): 465-75.
383 "Cancer genetics," as the geneticist Cliff Tabin: Tabin, interview with author, November 2009.
The Hallmarks of Cancer
384 I do not wish to achieve immortality: Eric Lax, Woody Allen and His Comedy (London: Elm Tree Books, 1976).
385 "The four molecular alterations accumulated": B. Vogelstein et al., "Genetic Alterations During Colorectal-Tumor Development," New England Journal of Medicine 319, no. 9 (1988): 525-32.
387 A tumor could thus "acquire" its own blood supply: Judah Folkman, "Angiogenesis," Annual Review of Medicine 57 (2006): 1-18.
387 Folkman's Harvard colleague Stan Korsmeyer: W. B. Graninger et al., "Expression of Bcl-2 and Bcl-2-Ig Fusion Transcripts in Normal and Neoplastic Cells," Journal of Clinical Investigation 80, no. 5 (1987): 1512-15. Also see Stanley J. Korsemeyer, "Regulators of Cell Death," 11, no. 3 (1995): 101-5.
390 In the fall of 1999, Robert Weinberg attended: Robert Weinberg, interview with author, January 2009.
390 In January 2000, a few months after their walk: Douglas Hanahan and Robert A. Weinberg, "The Hallmarks of Cancer," Cell 100, no. 1 (2000): 57-70.
390 "We discuss . . . rules that govern": Ibid.
392 "With holistic clarity of mechanism": Ibid. Also see Bruce Chabner, "Biological Basis for Cancer Treatment," Annals of Internal Medicine 118, no. 8 (1993): 633-37.
PART SIX:
THE FRUITS OF LONG ENDEAVORS
393 We are really reaping the fruits: Mike Gorman, letter to Mary Lasker, September 6, 1985, Mary Lasker Papers.
393 The National Cancer Institute, which has overseen: "To Fight Cancer, Know the Enemy," New York Times, August 5, 2009.
393 The more perfect a power is: See for instance St. Aquinas, Commentary on the Book of Causes, trans. Vincent Guagliardo et al. (CUA Press, 1996), 9.
"No one had labored in vain"
395 Have you met Jimmy?: Jimmy Fund solicitation pamphlet, 1963.
395 In the summer of 1997: "Einar Gustafson, 65, 'Jimmy' of Child Cancer Fund, Dies," New York Times, January 24, 2001; "Jimmy Found," People, June 8, 1998.
395 Only Sidney Farber had known: Phyllis Clauson, interview with author, 2009.
395 "Jimmy's story," she recalled: Ibid.
396 A few weeks later, in January 1998: Karen Cummings, interview with author, 2009.
396 And so it was in May 1998: Ibid.
397 "Everything has changed": Clauson, interview with author.
398 "How to overcome him became": Max Lerner, Wrestling with the Angel: A Memoir of My Triumph over Illness (New York: Touchstone, 1990), 26.
398 The poet Jason Shinder wrote, "Cancer": "The Lure of Death," New York Times, December 24, 2008.
400 "I've made a long voyage": Maxwell E. Perkins, "The Last Letter of Thomas Wolfe and the Reply to It," Harvard Library Bulletin, Autumn 1947, 278.
401 In 2005, an avalanche of papers: See, for example, Peter Boyle and Jacques Ferlay, "Mortality and Survival in Breast and Colorectal Cancer," Nature Reviews and Clinical Oncology 2 (2005): 424-25; Itsuro Yoshimi and S. Kaneko, "Comparison of Cancer Mortality (All Malignant Neoplasms) in Five Countries: France, Italy, Japan, UK and USA from the WHO Mortality Database (1960-2000)," Japanese Journal of Clinical Oncology 35, no. 1 (2005): 48-51; Alison L. Jones, "Reduction in Mortality from Breast Cancer," British Medical Journal 330, no. 7485 (2005): 205-6.
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br /> 401 The mortality for nearly every major: Eric J. Kort et al., "The Decline in U.S. Cancer Mortality in People Born Since 1925," Cancer Research 69 (2009): 6500-6505.
401 mortality had declined by about 1 percent: Ibid. Also see Ahmedin Jemal et al., "Cancer Statistics, 2005," CA: A Cancer Journal for Clinicians 55 (2005): 10-30; "Annual Report to the Nation on the Status of Cancer, 1975-2002," Journal of the National Cancer Institute, October 5, 2005.
401 between 1990 and 2005, the cancer-specific: Ibid.
401 more than half a million American men and women: American Cancer Society, Cancer Facts & Figures 2008 (Atlanta: American Cancer Society, 2008), 6.
402 Donald Berry, a statistician in Houston: Donald A. Berry, "Effect of Screening and Adjuvant Therapy on Mortality from Breast Cancer," New England Journal of Medicine 353, no. 17 (2005): 1784-92.
402 "No one," as Berry said: Donald Berry, interview with author, November 2009.
403 Mary Lasker died of heart failure: "Mary W. Lasker, Philanthropist for Medical Research, Dies at 93," New York Times, February 23, 1994.
403 the cancer geneticist Ed Harlow captured: Ed Harlow, "An Introduction to the Puzzle," Cold Spring Harbor Symposia on Quantitative Biology 59 (1994): 709-23.
404 In the winter of 1945, Vannevar Bush: Vannevar Bush, Science the Endless Frontier: A Report to the President by Vannevar Bush, Director of the Office of Scientific Research and Development, July 1945 (Washington, D.C.: U.S. Government Printing Office, 1945).
New Drugs for Old Cancers
405 In the story of Patroclus: Louise Gluck, The Triumph of Achilles (New York: Ecco Press, 1985), 16.
405 The perfect therapy has not been developed: Bruce Chabner letter to Rose Kushner, Rose Kushner Papers, Box 50.
408 In the summer of 1985: Laurent Degos, "The History of Acute Promyelocytic Leukaemia," British Journal of Haematology 122, no. 4 (2003): 539-53; Raymond P. Warrell et al., "Acute Promyelocytic Leukemia," New England Journal of Medicine 329, no. 3 (1993): 177-89; Huang Meng-er et al., "Use of All-Trans Retinoic Acid in the Treatment of Acute Promyelocytic Leukemia," Blood 72 (1988): 567-72.
409 "The nucleus became larger": Meng-er et al., "Use of All-Trans Retinoic Acid."
Siddhartha Mukherjee - The Emperor of All Maladies: A Biography of Cancer Page 65
