Happy Accidents: Serendipity in Major Medical Breakthroughs in the Twentieth Century (49 page)

3. R. L. Noble, “The discovery of the vinca alkaloids—chemotherapeutic agents against cancer,”
Biochem Cell Biol
68 (1990): 1344–51.

4. G. H. Svoboda, “A note on several alkaloids from
Vinca rosea
Linn. I. Leurosine, Virsine and Perivine,”
J Pharm Sci
47 (1958): 834.

5. The
Vinca
alkaloids do this by inhibiting the action of micro-tubules, structures that are required for separation of chromosomes at mitosis.

6. Mann,
Murder, Magic, and Medicine,
214.

C
HAPTER
12: A Heavy Metal Rocks: The Value of Platinum

1. B. Rosenberg, L. Van Camp, and T. Krigas, “Inhibition of cell division in
Escherichia coli
by electrolysis products from a platinum electrode,”
Nature
2906 (1965): 698–99.

2. Stephen J. Lippard, ed.,
Platinum, Gold, and Other Metal Chemo-therapeutic Agents: Chemistry and Biochemistry
(Washington, D.C.: American Chemical Society, 1983).

3. B. Rosenberg, “Platinum coordination complexes in cancer chemotherapy,”
Naturwissenchaften
60 (1973): 399–406.

C
HAPTER
13: Sex Hormones

1. C. Huggins and P. J. Clark, “Quantitative studies on prostatic secretion. II. The effect of castration and of estrogen injection on the normal and on the hyperplastic prostate gland of dogs,”
J Exp Med
72 (1940): 747–62.

2. A. Klopper and M. Hall, “New synthetic agent for the induction of ovulation: Preliminary trials in women,”
British Medical Journal
1 (1971): 152–54.

3. Early Breast Cancer Trialists’ Collaborative Group, “Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: An overview of the randomised trials,”
Lancet
365 (2005): 1687–717.

C
HAPTER
14: Angiogenesis: The Birth of Blood Vessels

1. G. H. Algire and H. W. Chalkley, “Vascular reactions of normal and malignant tissues in vivo; vascular reactions of mice to wounds and to normal and neoplastic transplants,”
J Natl Cancer Inst
6 (1945): 73–85.

2. Judah Folkman, “How is blood vessel growth regulated in normal and neoplastic tissue?” GHA Clowes Memorial Award lecture,
Cancer Research
46 (1986): 467–73.

3. Robert Cooke,
Dr. Folkman's War: Angiogenesis and the Struggle to Defeat Cancer
(New York: Random House, 2001).

4. Cooke,
Dr. Folkman's War,
83.

5. Cooke,
Dr. Folkman's War,
126.

6. J. Folkman and C. Haudenschild, “Angiogenesis in vitro,”
Nature
288 (1980): 551–56.

7. R. Langer, H. Brem, K. Falterman, M. Klein, and J. Folkman, “Isolation of a Cartilage Factor That Inhibits Tumor Neovascularization,”
Science
193 (1976): 70–72.

8. I. William Lane and Linda Comac,
Sharks Don't Get Cancer
(Garden City Park, N.Y.: Avery, 1992).

9. V. D. Herbert, “Laetrile: The Cult of Cyanide,”
Am J Clin Nutr
32 (1979): 1121–58.

10. C. G. Moertel, T. R. Fleming, J. Rubin, et al., “A clinical trial of amygdalin (Laetrile) in the treatment of human cancer,”
N Engl J Med
306 (1982): 201–6.

11. F. Rastinejad, P. J. Polverini, and N. P. Bouck, “Regulation of the activity of a new inhibitor of angiogenesis by a cancer suppressor gene,”
Cell
56 (1989): 345–55.

12. M. S. O'Reilly, L. Holmgren, Y. Shing, et al., “Angiostatin—a novel angiogenesis inhibitor that mediates the suppression of metastases by a Lewis lung-carcinoma,”
Cell
79 (1994): 315–28.

13. A new way of looking at many conditions on the basis of the mechanisms that underlie abnormal vessel growth stimulated research and clinical applications to a variety of diseases in many specialties besides oncology, including cardiology and vascular surgery, ophthalmology, hematology, and dermatology.

C
HAPTER
15: Aspirin Kills More than Pain

1. How cancers of the colon arise from its lining had been a matter of controversy for a long time. Many felt that it developed directly from one mutant cell dividing without restraint, to perhaps invade the structures of its wall. But the answer came in the 1960s and 1970s from a dedicated pathologist, Basil Morson, working alone at St. Mark's Hospital in London. This small hospital uniquely specialized in diseases of the colon and rectum and retained records of its patients dating back for generations. Morson, with keen diligence, established a fundamental truth: carcinomas arise within adenomatous polyps (benign tumors).

2. W. R. Waddell and R. W. Loughry, “Sulindac for polyposis of the colon,”
J Surg Oncol
24 (1983): 83–87.

3. F. M. Giardiello, S. R. Hamilton, A. J. Krush, S. Piantadosi, L. M. Hylind, P. Celano, S. V. Booker, C. R. Robinson, and G. J. A. Offerhaus, “Treatment of colonic and rectal adenomas with sulindac in familial adenomatous polyposis,”
N Engl J Med
328 (1993): 1313–16.

4. C. S. Williams, M. Tsujii, J. Reese, et al., “Host cyclooxygenase-2 modulates carcinoma growth,”
J Clin Invest
105 (2000): 1589–94.

C
HAPTER
16: Thalidomide: From Tragedy to Hope

1. Much of the thalidomide saga is told by Trent Stephens and Rock Brynner in
Dark Remedy: The Impact of Thalidomide and Its Revival as a Vital Medicine
(Cambridge, Mass.: Perseus, 2001).

2. W. G. McBride, “Thalidomide and Congenital Abnormalities,”
Lancet
2 (1961): 1358.

3. G. Rogerson, “Thalidomide and Congenital Abnormalities,”
Lancet
1 (1962): 691.

4. In the early 1960s a physician treating patients with Hansen's disease (leprosy) in Jerusalem, Dr. Jacob Sheskin, was caring for a patient with a severe inflammatory and agonizing complication known as ENL (erythema nodosum leprosum), characterized by large weeping boils all over the body and excruciating and unremitting pain. The patient had been sleepless for months, despite taking every existing sedative. As a last resort, Sheskin gave him thalidomide because he knew that certain mental patients, whom no other sleep aid had helped, had been effectively treated with it. Remarkably, not only did it allow the patient to sleep, but his pain vanished and his sores began to heal. Thalidomide is now the drug of choice for his condition. In 1998 the FDA approved it for treatment of ENL, which affects up to a couple hundred people in the United States. It is now known that it reduces inflammatory reactions by inhibiting the production of one of the body's self-destructive factors that provokes inflammation—tumor necrosis factor-alpha (TNF-?).

5. S. Singhal et al., “Antitumor activity of thalidomide in refractory multiple myeloma,”
N Engl J Med
341 (1999): 1565–71.

6. Another new drug found useful in multiple myeloma is Velcade. It was initially developed as a treatment for muscle-wasting conditions because it could prevent the destruction of proteins needed for healthy cell growth.

C
HAPTER
17: A Sick Chicken Leads to the Discovery of Cancer-Accelerating Genes

1.
Virus
means “poison” in Latin.

2. Peyton Rous, “A sarcoma of the fowl transmissible by an agent separable from the tumor cells,”
J Exp Med
13 (1911): 397–411.

3. In his 1925 novel about science,
Arrowsmith,
Sinclair Lewis based his character Rippleton Holabird upon Peyton Rous.

4. Some rejuvenation of interest was sparked when Burkitt's lymphoma, an unusual tumor of the lymph glands described in 1960, was found in 1982 to be caused by a retrovirus dubbed the Epstein-Barr virus.

5. J. Michael Bishop,
How to Win the Nobel Prize: An Unexpected Life in Science
(Cambridge, Mass.: Harvard University Press, 2003), 162.

6. D. Stehelin, H. E. Varmus, J. M. Bishop, and P. K. Vogt, “DNA Related to the Transforming Gene (s) of Rous Sarcoma Virus Is Present in Normal Avian DNA,”
Nature
260 (1976): 170–73.

7. Harold E. Varmus, “Retroviruses and Oncogenes I (Nobel Lecture),”
Angewandte Chemie
29 (1990): 710.

8. Controversy erupted when Dominique Stehelin, Bishop's postdoctoral fellow, demanded a share of the prize for the important experiments he had done with the two laureates, but the committee believed that the fundamental intellectual creativity belonged to Bishop and Varmus. Manifold contributions by others in the fields of medical genetics, tumor virology, and cell biology helped to pave the way for their research pursuits. Varmus's Nobel Prize acceptance speech was a model of attributions, as he cited more than forty other researchers whose work had led him and Bishop to their basis discoveries.

9. Quoted in profile of Harold Varmus by Natalie Angier,
New York Times,
November 21, 1993.

10. Quoted in Mariana Cook,
Faces of Science
(New York: W. W. Norton, 2005), 156.

11. Bishop, who felt that “one lifetime as a scientist is enough—great fun, but enough” (quoted in Paula McGuire, ed.,
Nobel Prize Winners: Supplement 1987–1991
[New York: H. W. Wilson, 1992]), became chancellor of the University of California at San Francisco.

C
HAPTER
18: A Contaminated Vaccine Leads to Cancer-Braking Genes

1. Richard Carter,
Breakthrough: The Saga of Jonas Salk
(New York: Trident, 1966), 1.

2. A. J. Levine, “The Road to the Discovery of the p53 protein,”
Int J Cancer
56 (1994): 775–76; A. J. Levine, “P53, the cellular gatekeeper for growth and division,”
Cell
88 (1997): 323–31; B. H. Sweet and M. R. Hilleman, “The vacuolating virus, SV40,”
Proc Soc Exp Biol
(New York) 105 (1960): 420–21.

3. S. J. Baker, R. White, E. Fearon, and B. Vogelstein, “Chromosome 17 Deletions and p53 Gene Mutations in Colorectal Carcinomas,”
Science
244 (1989): 217–21.

4. C. A. Finlay, P. W. Hinds, and A. J. Levine, “The p53 protooncogene can act as a suppressor of transformation,”
Cell
57 (1989): 1083–93.

5. Author interview with Arnold Levine, August 10, 1994.

6. Andrew Pollack, “Drugs May Turn Cancer Into Manageable Disease,”
New York Times,
June 6, 2004.

7. Robert A. Weinberg,
One Renegade Cell: How Cancer Begins
(New York: Basic Books, 1998), 161–64.

C
HAPTER
19: From Where It All Stems

1. E. A. McCulloch,
The Ontario Cancer Institute: Successes and Reverses at Sherbourne Street
(Montreal: McGill–Queen's University Press, 2003).

2. Author interview with Ernest McCulloch, January 25, 2006, and with James Till, February 21, 2006.

3. A. J. Becker, E. A. McCulloch, and J. E. Till, “Cytological demonstration of the clonal nature of spleen colonies derived from transplanted mouse marrow cells,”
Nature
197 (1963): 452–54.

4. Author interview with Ernest McCulloch, January 25, 2006.

5. Quoted in B. M. Kuehn and T. Hampton, “2005 Lasker Awards Honor Groundbreaking Biomedical Research Public Service,”
JAMA
294 (2005): 1327–30.

6. D. Rubio et al., “Spontaneous human adult cell transformation,”
Cancer Research
65 (2005): 3035.

7. E. A. McCulloch and J. E. Till, “Perspectives on the properties of stem cells,”
Nature Medicine
11 (2005): 1026–28.

8. In 1988 Lewis Thomas made a similar assessment of the scientific method: “I have never been quite clear in my mind about what this means. ‘Method’ has the sound of an orderly, preordained, step-by-step process…. I do not believe it really works that way most of the time…. More often than not, the step-by-step process begins to come apart, because of what almost always seemed a piece of luck, good or bad, for the scientist; something unpredicted and surprising turned up, forcing the work to veer off in a different direction. Surprise is what scientists live for….The very best ones revel in surprise, dance in the presence of astonishment.” Lewis Thomas, foreword to
Natural Obsessions: The Search for the Oncogene,
by Natalie Angier (Boston: Houghton Mifflin, 1988), xiii–xiv.