The Emperor of All Maladies: A Biography of Cancer (103 page)

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Authors: Siddhartha Mukherjee

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BOOK: The Emperor of All Maladies: A Biography of Cancer
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322
“You marketed this coverage to her”:
Ibid., 307.

323
In August 1992, Nelene Fox:
Ibid., 309.

323
“The dose-limiting barrier”:
S. Ariad and W. R. Bezwoda, “High-Dose Chemotherapy: Therapeutic Potential in the Age of Growth Factor Support,”
Israel Journal of Medical Sciences
28, no. 6 (1992): 377–85.

323
In Johannesburg, more than 90 percent:
W. R. Bezwoda, L. Seymour, and R. D. Dansey, “High-Dose Chemotherapy with Hematopoietic Rescue as Primary Treatment for Metastatic Breast Cancer: A Randomized Trial,”
Journal of Clinical Oncology
13, no. 10 (1995): 2483–89.

324
On April 22, eleven months after:
Lief and Caldwell,
And the Walls Came Tumbling Down
, 309.

324
In 1993 alone:
Papers were assessed on www.pubmed.org.

324
“If all you have is a cold or the flu”:
Lief and Caldwell,
And the Walls Came Tumbling Down
, 234.

324
On the morning of December 28, 1993:
Ibid.

324
That evening, it returned a verdict:
“$89 Million Awarded Family,”
New York Times.

325
In Massachusetts, Charlotte Turner:
“Cancer Patient’s Kin Sues Fallon” and “Coverage Denied for Marrow Transplant,”
Worcester (MA) Telegram & Gazette
, December 7, 1995; Erin Dominique Williams and Leo Van Der Reis,
Health Care at the Abyss: Managed Care vs. the Goals of Medicine
(Buffalo, NY: William S. Hein Publishing, 1997), 3.

325
Between 1988 and 2002:
See Richard Rettig et al., eds.,
False Hope: Bone Marrow Transplantation for Breast Cancer
(New York: Oxford University Press, 2007), 85, and Table 3.2.

325
“complicated, costly and potentially dangerous”:
Bruce E. Brockstein and Stephanie F. Williams, “High-Dose Chemotherapy with Autologous Stem Cell Rescue for Breast Cancer: Yesterday, Today and Tomorrow,”
Stem Cells
14, no. 1 (1996): 79–89.

325
Between 1991 and 1999, roughly forty thousand:
JoAnne Zujewski, Anita Nelson, and Jeffrey Abrams, “Much Ado about Not . . . Enough Data,”
Journal of the National Cancer Institute
90 (1998): 200–209. Also see Rettig et al.,
False Hope
, 137.

326
“Transplants, transplants, everywhere”:
Robert Mayer, interview with author, July 2008.

326
As Bezwoda presented the data:
W. R. Bezwoda, “High Dose Chemotherapy with Haematopoietic Rescue in Breast Cancer,”
Hematology and Cell Therapy
41, no. 2 (1999): 58–65. Also see Werner Bezwoda, plenary session, American Society of Clinical Oncology meeting, 1999 (video recordings available at www.asco.org).

326
three other trials presented that afternoon:
Ibid.

326
At Duke, embarrassingly enough:
Ibid.

326
“even a modest improvement”:
Ibid.

326
A complex and tangled trial from Sweden:
Ibid.

326
“My goal here,” one discussant began:
Ibid.

327
“People who like to transplant will continue to transplant”:
“Conference Divided over High-Dose Breast Cancer Treatment,”
New York Times
, May 19, 1999.

327
Investigation of Bezwoda’s breast cancer study: Raymond B. Weiss et al., “High-Dose Chemotherapy for High-Risk Primary Breast Cancer: An On-Site Review of the Bezwoda Study,”
Lancet
355, no. 9208 (2000): 999–1003.

328
Another patient record, tracked back to its origin:
“Bezwoda,” Kate Barry (producer), archived in video format at http://beta.mnet.co.za/Carteblanche, M-Net TV Africa (March 19, 2000).

328
“I have committed a serious breach of scientific honesty”:
“Breast Cancer Study Results on High-Dose Chemotherapy Falsified,” Imaginis, February 9, 2000, http://www .imaginis.com/breasthealth/news/news2.09.00.asp (accessed January 2, 2010).

328
“By the late 1990s, the romance was already over”:
Robert Mayer, interview with author.

328
Maggie Keswick Jencks:
Maggie Keswick Jencks,
A View from the Front Line
(London, 1995).

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 über Plfanzenhybriden,”
Verhandlungen des Naturforschenden Vereines in Brünn
.
IV für 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, Hilário de Gouvêa:
A. N. Monteiro and R. Waizbort, “The Accidental Cancer Geneticist: Hilário de Gouvêa 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 Cell,”
Nobel Lectures, Physiology or Medicine, 1963–1970
(Amsterdam: Elsevier Publishing Company, 1972).

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