The Emperor of All Maladies: A Biography of Cancer (105 page)

415
In the summer of 1986:
Bazell,
Her-2
, and Dennis Slamon, interview with author, April 2010.

415
Dennis Slamon, a UCLA oncologist:
Ibid.

415
a “velvet jackhammer”:
Eli Dansky, “Dennis Slamon: From New Castle to New Science,”
SU2C Mag
, http://www.standup2cancer.org/node/194 (accessed January 24, 2010).

415
“a murderous resolve”
: Ibid.

415
In Chicago, Slamon had performed a series:
See, for example, I. S. Chen et al., “The x Gene Is Essential for HTLV Replication,”
Science
229, no. 4708 (1985): 54–58; W. Wachsman et al., “HTLV x Gene Mutants Exhibit Novel Transcription Regulatory Phenotypes,”
Science
235, no. 4789 (1987): 647–77; C. T. Fang et al., “Detection of Antibodies to Human T-Lymphotropic Virus Type 1 (HTLV-1),”
Transfusion
28, no. 2 (1988): 179–83.

415
If Ullrich sent him the DNA probes:
Details of the Ullrich and Slamon collaboration
are outlined in Bazell,
Her-2
, and from Slamon, interview with author.

416
In a few months:
D. Slamon et al., “Human Breast Cancer: Correlation of Relapse and Survival with Amplification of the Her-2/Neu Oncogene,”
Science
235 (1987): 177–82.

417
In the mid-1970s, two immunologists at Cambridge University:
See
Nobel Lectures, Physiology or Medicine, 1981
–
1990
, ed. Jan Lindsten (Singapore: World Scientific Publishing, 1993).

418
“allergic to cancer”:
Merrill Goozner,
The $800 Million Pill: The Truth Behind the Cost of New Drugs
(Berkeley: University of California Press, 2004), 195.

418
Drained and dejected:
Ibid.

418
“Nobody gave a shit”:
Bazell,
Her-2
, 49.

419
“When I was finished with all that”:
Ibid. Also Barbara Bradfield, interview with author, July 2008.

419
But there was more river to ford:
Ibid.

420
“His tone changed,” she recalled:
Ibid.

420
“I was at the end of my road”:
Ibid

420
“Survivors look back and see omens”:
Joan Didion,
The Year of Magical Thinking
(New York: Vintage, 2006), 152.

420
On a warm August morning in 1992:
Bradfield, interview with author. Details of the trial and the treatment are from Bradfield’s interview, from Bazell’s
Her-2
, and from Slamon, interview with author, April 2010.

Drugs, Bodies, and Proof

423
Dying people don’t have time or energy:
“Dying for Compassion,”
Breast Cancer Action Newsletter
31 (August 1995).

423
It seemed as if we had:
Musa Mayer,
Breast Cancer Action Newsletter
80 (February/March 2004).

423
“True success happens”:
Breast Cancer Action Newsletter
32 (October 1995).

424
The number of women enrolled in these trials:
Robert Bazell,
Her-2: The Making of Herceptin, a Revolutionary Treatment for Breast Cancer
(New York: Random House, 1998), 160–80.

424
“We do not provide . . . compassionate use”:
Ibid., 117.

424
“If you start making exceptions”:
Ibid., 127.

424
“Why do women dying of breast cancer”:
“Dying for Compassion,”
Breast Cancer Action Newsletter.

424
“Scientific uncertainty is no excuse”:
Charlotte Brody et al., “Rachel’s Daughters, Searching for the Causes of Breast Cancer: A Light-Saraf-Evans Production Community Action & Resource Guide,” http://www.wmm.com/filmCatalog/study/rachelsdaughters.pdf (accessed January 31, 2010).

424
Marti Nelson, for one, certainly could not:
Marti Nelson’s case and its aftermath are described in Bazell,
Her-2.

427
On Sunday, May 17:
Bruce A. Chabner, “ASCO 1998: A Commentary,”
Oncologist
3, no. 4 (1998): 263–66; D. J. Slamon et al., “Addition of Herceptin to First-Line Chemotherapy for HER-2 Overexpressing Metastatic Breast Cancer Markedly Increases Anti-Cancer Activity: A Randomized, Multinational Controlled Phase III Trial (abstract 377),”
Proceedings of the American Society of Clinical Oncology 16
(1998): 377.

427
In the pivotal 648 study:
Slamon et al., “Addition of Herceptin to First-Line Chemotherapy,” 377.

428
In 2003, two enormous multinational studies:
Romond et al. and Piccart-Gebhart et al.,
New England Journal of Medicine
353 (2005): 1659–84.

428
“The results,” one oncologist wrote:
Gabriel Hortobagyi, “Trastuzumab in the treatment of breast cancer,” editorial,
New England Journal of Medicine
, 353, no. 16 (2005): 1734.

428
“The company,” Robert Bazell, the journalist:
Bazell,
Her-2
, 180–82.

A Four-Minute Mile

430
The nontoxic curative compound:
James F. Holland, “Hopes for Tomorrow versus Realities of Today: Therapy and Prognosis in Acute Lymphocytic Leukemia of Childhood,”
Pediatrics
45:191–93.

430
Why, it is asked, does the supply of new miracle drugs:
Lewis Thomas,
The Lives of a Cell
(New York: Penguin, 1978), 115.

430
This abnormality, the so-called Philadelphia chromosome:
John M. Goldman and Junia V. Melo, “Targeting the BCR-ABL Tyrosine Kinase in Chronic Myeloid Leukemia,”
New England Journal of Medicine
344, no. 14 (2001): 1084–86.

431
The identity of the gene:
Annelies de Klein et al., “A Cellular Oncogene Is Translocated to the Philadelphia Chromosome in Chronic Myelocitic Leukemia,”
Nature
300, no. 5894 (1982): 765–67.

431
The mouse developed the fatal spleen-choking:
E. Fainstein et al., “A New Fused Transcript in Philadelphia Chromosome Positive Acute Lymphocytic Leukaemia,”
Nature
330, no. 6146 (1987): 386–88; Nora Heisterkamp et al., “Structural Organization of the Bcr Gene and Its Role in the Ph’ Translocation,”
Nature
315, no. 6022 (1985): 758–61; de Klein et al., “Cellular Oncogene Is Translocated”; Nora Heisterkamp et al., “Chromosomal Localization of Human Cellular Homologues of Two Viral Oncogenes,”
Nature
299, no. 5885 (1982): 747–49.

431
In the mid-1980s:
Daniel Vasella and Robert Slater,
Magic Cancer Bullet: How a Tiny Orange Pill Is Rewriting Medical History
(New York: HarperCollins, 2003), 40–48; Elisabeth Buchdunger and Jürg Zimmermann, “The Story of Gleevec,” innovation.org, http://www.innovation.org/index.cfm/StoriesofInnovation/InnovatorStories/The_Story_of_Gleevec (accessed January 31, 2010).

433
Jürg Zimmermann, a talented chemist:
Howard Brody,
Hooked: Ethics, the Medical Profession, and the Pharmaceutical Industry
(Lanham, MD: Rowman & Littlefield, 2007), 14–15; Buchdunger and Zimmermann, “Story of Gleevec.”

433
“[It was] what a locksmith does”:
Buchdunger and Zimmermann, “Story of Gleevec.”

433
“I was drawn to oncology as a medical student”:
Brian Druker, interview with author, November 2009.

434
In 1993, he left Boston
: Ibid.

434
“Everyone just humored me”:
Ibid.

434
In October 1992, just a few months
: Ibid.

435
“Although freedom from leukemia”:
S. Tura et al., “Evaluating Survival After Allogeneic Bone Marrow Transplant for Chronic Myeloid Leukaemia in Chronic Phase: A Comparison of Transplant Versus No-Transplant in a Cohort of 258 Patients First Seen
in Italy Between 1984 and 1986,”
British Journal of Haematology
85 (1993): 292–99.

435
“Cancer is complicated”:
Druker, interview with author.

435
In the summer of 1993, when Lydon’s drug:
Ibid.

435
Druker described the findings in the journal:
Brian J. Druker, “Effects of a Selective Inhibitor of the Abl Tyrosine Kinase on the Growth of Bcr-Abl Positive Cells,”
Nature Medicine
2, no. 5 (1996): 561–66.

436
“The drug . . . would never work”:
The story of Gleevec’s development is from Druker, interview with author.

436
In early 1998, Novartis finally relented:
Lauren Sompayrac,
How Cancer Works
(Sudbury, MA: Jones and Bartlett, 2004), 21.

438
Druker edged into higher and higher:
Brian J. Druker et al., “Efficacy and Safety of a Specific Inhibitor of the BCR-ABL Tyrosine Kinase in Chronic Myeloid Leukemia,”
New England Journal of Medicine
344, no. 14 (2001): 1031–37.

438
Of the fifty-four patients:
Ibid.

438
“Before the year 2000”:
Hagop Kantarjian, Georgetown Oncology Board Review Lectures, 2008.

439
“When I was a youngster in Illinois”:
Bruce A. Chabner, “The Oncologic Four-Minute Mile,”
Oncologist
6, no. 3 (2001): 230–32.

439
“It proves a principle”:
Ibid.

The Red Queen’s Race

441
“Well, in our country,” said Alice:
Lewis Carroll,
Alice in Wonderland and Through the Looking Glass
(Boston: Lothrop, 1898), 125.

441
In August 2000:
Details of Jerry Mayfield’s case are from the CML blog newcmldrug .com. This website is run by Mayfield to provide information to patients about CML and targeted therapy.

442
CML cells, Sawyers discovered:
See for instance M. E. Gorre et al., “Clinical Resistance to STI-571 Cancer Therapy Caused by BCR-ABL Gene Mutation or Amplification,”
Science
293, no. 5531 (2001): 876–80; Neil P. Shah et al., “Multiple
BCR-ABL
Kinase Domain Mutations Confer Polyclonal Resistance to the Tyrosine Kinase Inhibitor Imatinib (STI571) in Chronic Phase and Blast Crisis Chronic Myeloid Leukemia,”
Cancer Cell
2, no. 2 (2002): 117–25.

442
“an arrow pierced through the center of the protein’s heart”:
Attributed to John Kuriyan; quoted by George Dmitri to the author at a Columbia University seminar, November 2009.

442
In 2005, working with chemists:
Jagabandhu Das et al., “2-Aminothiazole as a Novel Kinase Inhibitor Template. Structure-Activity Relationship Studies toward the Discovery of
N
-(2-Chloro-6-methylphenyl)-2-[[6-[4-(2-hydroxyethyl)-1-(piperazinyl)]-2-methyl-4-pyrimidinyl](amino)]-1,3-thiazole-5-carboxamide (Dasatinib, BMS-354825) as a Potent
pan
-Src Kinase Inhibitor,”
Journal of Medicinal Chemistry
49, no. 23 (2006): 6819–32; Neil P. Shah et al., “Overriding Imatinib Resistance with a Novel ABL Kinase Inhibitor,”
Science
305, no. 5682 (2004): 399–401; Moshe Talpaz et al., “Dasatinib in Imatinib-Resistant Philadelphia Chromosome–Positive Leukemias,”
New England Journal of Medicine
354, no. 24 (2006): 2531–41.

443
twenty-four novel drugs:
For a full list, see National Cancer Institute, targeted therapies list, http://www.cancer.gov/cancertopics/factsheet/Therapy/targeted (accessed
February 23, 2010). This website also details the role of such drugs as Avastin and bortezomib.

443
Over a decade:
“Velcade (Bortezomib) Is Approved for Initial Treatment of Patients with Multiple Myeloma,” U.S. Food and Drug Administration, http://www.fda.gov/AboutFDA/CentersOffices/CDER/ucm094633.htm (accessed January 31, 2010); “FDA Approval for Lenalidomide,” National Cancer Institute, U.S. National Institutes of Health, http://www.cancer.gov/cancertopics/druginfo/fda-lenalidomide (accessed January 31, 2010).

444
In 1948, epidemiologists identified a cohort:
Framingham Heart Study, the National Heart, Lung and Blood Institute and Boston University, http://www.framinghamheartstudy.org/ (accessed January 31, 2010).

445
In May 2008, two Harvard epidemiologists:
Nicholas A. Christakis, “The Collective Dynamics of Smoking in a Large Social Network,”
New England Journal of Medicine
358, no. 21 (2008): 2249–58.

447
“Cancer at the
fin de siècle”: Harold J. Burstein, “Cancer at the
Fin de Siècle,
”
Medscape Today
, February 1, 2000, http://www.medscape.com/viewarticle/408448 (accessed January 31, 2010).

Thirteen Mountains

448
“Every sickness is a musical problem”:
W. H. Auden, “The Art of Healing (
In Memoriam David Protetch, M.D.
),”
New Yorker
, September 27, 1969.

448
The revolution in cancer research:
Bert Vogelstein and Kenneth Kinzler, “Cancer Genes and the Pathways They Control,”
Nature Medicine
10, no. 8 (2004): 789–99.

449
“The purpose of my book”:
Susan Sontag,
Illness as Metaphor and AIDS and Its Metaphors
(New York: Picador, 1990), 102.

450
The Human Genome Project:
“Once Again, Scientists Say Human Genome Is Complete,”
New York Times
, April 15, 2003.

450
the Cancer Genome Atlas:
“New Genome Project to Focus on Genetic Links in Cancer,”
New York Times
, December 14, 2005.

450
“When applied to the 50 most common”:
“Mapping the Cancer Genome,”
Scientific American
, March 2007.

450
In 2006, the Vogelstein team revealed:
Tobias Sjöblom et al., “The Consensus Coding Sequences of Human Breast and Colorectal Cancers,”
Science
314, no. 5797 (2006): 268–74.