The Cancer Chronicles (34 page)

1.
experimenting with fruit flies:
H. J. Muller, “Artificial Transmutation of the Gene,”
Science
66, no. 1699 (July 22, 1927): 84–87. [
http://www.sciencemag.org/content/66/1699/84.short
]

2.
discovered in his monastery garden:
An English translation of Gregor Mendel’s landmark paper, “Experiments in Plant Hybridization” (1865), can be found online at MendelWeb. [
http://www.mendelweb.org/Mendel.html
]

3.
That kind of clarity:
The experiments by Avery, Hershey, and Chase, and the discovery of DNA’s double-helical structure, are described in Horace Freeland
Judson’s
The Eighth Day of Creation: Makers of the Revolution in Biology,
expanded ed. (Cold Spring Harbor, NY: Cold Spring Harbor Laboratory Press, 1996). The seminal papers include Oswald T. Avery, Colin M. MacLeod, and Maclyn McCarty, “Studies on the Chemical Nature of the Substance Inducing Transformation of Pneumococcal Types,”
The Journal of Experimental Medicine
79, no. 2 (February 1, 1944): 137–58 [
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2135445
]; A. D. Hershey and M. Chase, “Independent Functions of Viral Protein and Nucleic Acid in Growth of Bacteriophage,”
The Journal of General Physiology
36, no. 1 (May 1952): 39–56 [
http://www.ncbi.nlm.nih.gov/pubmed/12981234
]; and J. D. Watson and F. H. C. Crick, “A Structure for Deoxyribose Nucleic Acid,”
Nature
171 (1953): 737–38. An annotated version of Watson and Crick’s paper can be found on the website for the Exploratorium. See “Origins, Unwinding DNA, Life at Cold Spring Harbor Laboratory.” [
http://www.exploratorium.edu/origins/coldspring/ideas.
]

4.
x-rays were first produced:
For a translation of the original paper see W. C. Röntgen, “On a New Kind of Rays” (1895), republished in Wilhelm Conrad Röntgen, Sir George Gabriel Stokes, and Sir Joseph John Thomson,
Röntgen Rays: Memoirs by Röntgen, Stokes, and J. J. Thomson
(New York: Harper & Brothers, 1899), 3–13. The collection also includes Röntgen’s second and third communications. Like the Curies, he had no reason yet to be fearful of ionizing radiation. He matter-of-factly describes what happens when he shines x-rays into his eyes (pp. 7 and 39–40). [
http://books.google.com/books?id=m0hWAAAAMAAJ
]

5.
strange-looking chromosomes:
For Boveri’s speculations about cancer cells, see “Concerning the Origin of Malignant Tumours,” a translation by Henry Harris of Boveri’s
Zur Frage der Entstehung maligner Tumoren
(1914),
Journal of Cell Science
121 (January 1, 2008): 1–84. [
http://jcs.biologists.org/content/121/Supplement_1/1.full
] It has also been published as a book: Theodor Boveri,
Concerning the Origin of Malignant Tumours,
1st ed. (Cold Spring Harbor, NY: Cold Spring Harbor Laboratory Press, 2007).

6.
to “multiply without restraint”:
Boveri, “Concerning the Origin.”

7.
“conceivable at least that mammalian cancer”:
Volker Wunderlich, “Early References to the Mutational Origin of Cancer,”
International Journal of Epidemiology
36, no. 1 (February 1, 2007): 246–47. [
http://ije.oxfordjournals.org/content/36/1/246.short
]

8.
“a new kind of cell”:
Wunderlich, “Early References.”

9.
Becquerel accidentally discovered:
“On Radioactivity, a New Property of Matter,”
Nobel Lectures, Physics 1901–1921
(Amsterdam: Elsevier Publishing Company, 1967), 52–70. This lecture, delivered on December 11, 1903, is available on the Nobel Prize website. [
http://www.nobelprize.org/nobel_prizes/physics/laureates/1903/becquerel-lecture.html
]

10.
Marie Curie noticed:
The Curies’ experiments are described in Pierre Curie’s June 6, 1905 Nobel lecture, “Radioactive Substances, Especially Radium,” in
Nobel Lectures, Physics 1901–1921
(Amsterdam: Elsevier Publishing Company, 1967). Available at the Nobel Prize website. [
http://www.nobelprize.org/nobel_prizes/physics/laureates/1903/pierre-curie-lecture.html
] Also see Eve Curie,
Madame Curie: A Biography,
trans. Vincent Sheean (Garden City, NY: Doubleday,
Doran & Co., 1937); and Barbara Goldsmith,
Obsessive Genius: The Inner World of Marie Curie
(New York: W. W. Norton, 2005).

11.
“a kind of matter in the world”:
The film with Greer Garson and Walter Pidgeon was nominated for the 1944 Academy Award for Outstanding Motion Picture. (The winner was
Casablanca.
)

12.
“One of our joys”:
Marie Curie,
Pierre Curie (With the Autobiographical Notes of Marie Curie),
trans. Charlotte Kellogg (New York: Macmillan Co., 1923), 187.

13.
an optical analog of a sonic boom:
More specifically the Curies were seeing Cherenkov radiation.

14.
decorate their teeth, fingernails, and eyebrows:
For reports on the Radium Girls, see Frederick L. Hoffman, “Radium (Mesothorium) Necrosis,”
Journal of the American Medical Association
85, no. 13 (1925): 961–65 [
http://jama.ama-assn.org/content/85/13/961
]; R. E. Rowland, Radium in Humans: A Review of U.S. Studies, Argonne National Laboratory, Environmental Research Division, 1994; [
http://www.ustur.wsu.edu/Radium/files/RaInHumans.pdf
] and Ross Mullner,
Deadly Glow: The Radium Dial Worker Tragedy
(Washington, DC: American Public Health Association, 1999).

15.
“soot warts”:
“Cancer Scroti,” in
The Chirurgical Works of Percival Pott,
vol. 3 (London: Johnson, 1808), 177–80. [
http://books.google.com/books/about/The_chirurgical_works_of_Percival_Pott.html?id=cvS_o4-jIzwC
]

16.
The same cancer was later found:
H. A. Waldron, “A Brief History of Scrotal Cancer,”
British Journal of Industrial Medicine
40, no. 4 (November 1983): 390–401. [
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1009212
]

17.
applying coal tar to rabbits’ ears:
K. Yamagiwa and K. Ichikawa, “Experimental Study of the Pathogenesis of Carcinoma,”
Journal of Cancer Research
3 (1918): 1–29. Republished in
CA: A Cancer Journal for Clinicians
27, no. 3 (December 31, 2008): 174–81. [
http://onlinelibrary.wiley.com/doi/10.3322/canjclin.27.3.174/abstract
]

18.
produced tumors in laboratory animals:
See, for example, J. W. Cook, C. L. Hewett, and I. Hieger, “The Isolation of a Cancer-producing Hydrocarbon from Coal Tar,”
Journal of the Chemical Society
(January 1, 1933): 395–405. [
http://pubs.rsc.org/en/content/articlelanding/1933/jr/jr9330000395
]

19.
the Ames test:
Bruce N. Ames et al., “Carcinogens Are Mutagens: A Simple Test System Combining Liver Homogenates for Activation and Bacteria for Detection,”
Proceedings of the National Academy of Sciences
70, no. 8 (August 1973): 2281–85. [
http://www.pnas.org/content/70/8/2281.abstract
]

20.
studying chicken tumors:
Peyton Rous’s papers are “A Transmissible Avian Neoplasm,”
Journal of Experimental Medicine
12, no. 5 (September 1, 1910): 696–705 [
http://www.ncbi.nlm.nih.gov/pubmed/19867354
] and “A Sarcoma of the Fowl Transmissible by an Agent Separable from the Tumor Cells,”
Journal of Experimental Medicine
13, no. 4 (April 1, 1911): 397–411. [
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2124874
]

21.
src, ras, fes, myb, myc
:
The string of revelations, which has been described as
the Revolution of 1976, was set off by Harold Varmus and J. Michael Bishop (D. Stehelin, H. E. Varmus, J. M. Bishop, and P. K. Vogt, “DNA Related to the Transforming Gene(s) of Avian Sarcoma Viruses Is Present in Normal Avian DNA,”
Nature
260, no. 5547 [March 11, 1976]: 170–73) [
http://dx.doi.org/10.1038/260170a0
] and is described in Robert Weinberg’s
One Renegade Cell: The Quest for the Origin of Cancer
(New York: Basic Books, 1999). I also referred to Weinberg’s “How Cancer Arises,”
Scientific American
275, no. 3 (September 1996): 62–70; Douglas Hanahan and R. A. Weinberg, “The Hallmarks of Cancer,”
Cell
100, no. 1 (January 7, 2000): 57–70; and D. Hanahan and R. A. Weinberg, “Hallmarks of Cancer: The Next Generation,”
Cell
144, no. 5 (March 4, 2011): 646–74. Natalie Angier told Weinberg’s story in
Natural Obsessions: Striving to Unlock the Deepest Secrets of the Cancer Cell
(New York: Warner Books, 1989), and Weinberg gave his own account in
Racing to the Beginning of the Road: The Search for the Origin of Cancer
(New York: Harmony, 1996).

22.
they were named proto-oncogenes:
C. Shih, R. A. Weinberg, et al., “Passage of Phenotypes of Chemically Transformed Cells via Transfection of DNA and Chromatin,”
Proceedings of the National Academy of Sciences
76, no. 11 (November 1979): 5714–18 [
http://www.ncbi.nlm.nih.gov/pubmed/230490
]; and C. J. Tabin, R. A. Weinberg, et al., “Mechanism of Activation of a Human Oncogene,”
Nature
300, no. 5888 (November 11, 1982): 143–49. [
http://www.ncbi.nlm.nih.gov/pubmed/6290897
]

23.
Some mutations are even more wrenching:
The best known example is the Philadelphia chromosome, which is involved in chronic myeloid leukemia. For the original report, see
Peter Nowell and David Hungerford, “A Minute Chromosome in Chronic Granulocytic Leukemia,”
Science
132, no. 3438 (November 1960): 1497.

24.
when a gene called
Rb
:
S. H. Friend, R. A. Weinberg, et al., “A Human DNA Segment with Properties of the Gene That Predisposes to Retinoblastoma and Osteosarcoma,”
Nature
323, no. 6089 (October 16, 1986): 643–46 [
http://www.ncbi.nlm.nih.gov/pubmed/2877398
]; and J. A. DeCaprio et al., “The Product of the Retinoblastoma Susceptibility Gene Has Properties of a Cell Cycle Regulatory Element,”
Cell
58, no. 6 (September 22, 1989): 1085–95. [
http://www.ncbi.nlm.nih.gov/pubmed/2673542
]

25.
both copies must be knocked out:
This is known as the two-hit hypothesis. See
Alfred G. Knudson, “Mutation and Cancer: Statistical Study of Retinoblastoma,”
Proceedings of the National Academy of Sciences
68, no. 4 (April 1971): 820–23. [
http://www.ncbi.nlm.nih.gov/pubmed/5279523
]

26.
involved in the timekeeping:
See, for example, DeCaprio et al., “The Product of the Retinoblastoma Susceptibility Gene.” [
http://www.ncbi.nlm.nih.gov/pubmed/2673542
]

27.
sits at the center of a web:
C. A. Finlay, P. W. Hinds, and A. J. Levine, “The P53 Proto-oncogene Can Act as a Suppressor of Transformation,”
Cell
57, no. 7 (June 30, 1989): 1083–93 [
http://www.ncbi.nlm.nih.gov/pubmed/2525423
]; and M. B. Kastan, B.
Vogelstein, et al., “Participation
of P53 Protein in the Cellular Response to DNA Damage,” part 1,
Cancer Research
51, no. 23 (December 1, 1991): 6304–11. [
http://www.ncbi.nlm.nih.gov/pubmed/1933891
]

28.
programmed cell death, or apoptosis:
J. F. Kerr, A. H. Wyllie, and A. R. Currie, “Apoptosis: A Basic Biological Phenomenon with Wide-ranging Implications in Tissue Kinetics,”
British Journal of Cancer
26, no. 4 (August 1972): 239–57. [
http://www.ncbi.nlm.nih.gov/pubmed/4561027
]

29.
a principle called the Hayflick limit:
L. Hayflick and P. S. Moorhead, “The Serial Cultivation of Human Diploid Cell Strains,”
Experimental Cell Research
25, no. 3 (December 1961): 585–621. [
http://www.sciencedirect.com/science/article/pii/0014482761901926
]

30.
The count is kept by telomeres:
The story of the discovery is told in Elizabeth H. Blackburn, Carol W. Greider, and Jack W. Szostak, “Telomeres and Telomerase: The Path from Maize, Tetrahymena and Yeast to Human Cancer and Aging,”
Nature Medicine
12, no. 10 (October 2006): 1133–38. [
http://www.ncbi.nlm.nih.gov/pubmed/17024208
] The key papers are J. W. Szostak and E. H. Blackburn, “Cloning Yeast Telomeres on Linear Plasmid Vectors,”
Cell
29, no. 1 (May 1982): 245–55 [
http://www.ncbi.nlm.nih.gov/pubmed/6286143
]; C. W. Greider and E. H. Blackburn, “Identification of a Specific Telomere Terminal Transferase Activity in Tetrahymena Extracts,
Cell
43(1985): 405–13 [
http://www.ncbi.nlm.nih.gov/pubmed/3907856
]; and C. W. Greider and E. H. Blackburn, “A Telomeric Sequence in the RNA of Tetrahymena Telomerase Required for Telomere Repeat Synthesis,”
Nature
337 (1989): 331–37. [
http://www.nature.com/nature/journal/v337/n6205/abs/337331a0.html
]

31.
accumulating mutations:
Accelerating the process may be a phenomenon called genomic instability. See Simona Negrini, Vassilis G. Gorgoulis, and Thanos D. Halazonetis, “Genomic Instability—An Evolving Hallmark of Cancer,”
Nature Reviews Molecular Cell Biology
11, no. 3 (March 1, 2010): 220–28. [
http://www.nature.com/nrm/journal/v11/n3/abs/nrm2858.html
]

32.
As this evolution unfolds:
For an overview of the phenomenon, see Hanahan and Weinberg’s “The Hallmarks of Cancer” and “Hallmarks of Cancer: The Next Generation.”