The Emperor of All Maladies: A Biography of Cancer (104 page)

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.

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.”

410
In 1982, a postdoctoral scientist:
Robert Bazell,
Her-2: The Making of Herceptin, a Revolutionary Treatment for Breast Cancer
(New York: Random House, 1998), 17.

411
“It would have been an overnight test”:
Ibid.

411
although Padhy’s discovery was published:
Lakshmi Charon Padhy et al., “Identification of a Phosphoprotein Specifically Induced by the Transforming DNA of Rat Neuroblastomas,”
Cell
28, no. 4 (1982): 865–71.

A City of Strings

412
In Ersilia, to establish the relationships:
Italo Calvino,
Invisible Cities
(Boston: Houghton Mifflin Harcourt, 1978), 76.

412
In his book
Invisible Cities: Ibid.

413
In the summer of 1984:
Robert Bazell,
Her-2: The Making of Herceptin, a Revolutionary Treatment for Breast Cancer
(New York: Random House, 1998).

414
In 1982, Genentech unveiled the first
: “A New Insulin Given Approval for Use in U.S.,”
New York Times
, October 30, 1982.

414
in 1984, it produced a clotting factor:
“Genentech Corporate Chronology,” http://www .gene.com/gene/about/corporate/history/timeline.html (accessed January 30, 2010).

414
in 1985, it created a recombinant version:
Ibid.

414
It was under the aegis:
L. Coussens et al., “3 Groups Discovered the Neu Homolog (Her-2, Also Called Erb-b2),”
Science
230 (1985): 1132–39. Also see T. Yamamoto et al.,
Nature
319 (1986): 230–34, and C. King et al.,
Science
229 (1985): 974–76.