42. Beauty Beyond Belief: Packaged and sold by BBB Seed, Boulder, Colorado. [http://www.bbbseed.com]
CHAPTER 5 Information Sickness
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.n
cbi.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.”
33. signals are sent to healthy cells: These discoveries grew from early research on the role of the tumor microenvironment. See, for example, D. S. Dolberg and M. J. Bissell, “Inability of Rous Sarcoma Virus to Cause Sarcomas in the Avian Embryo,” Nature 309, no. 5968 (June 7, 1984): 552–56 [http://www.ncbi.nlm.nih.gov/pubmed/6203040]; and D. S. Dolberg, M. J. Bissell, et al., “Wounding and Its Role in RSV-mediated Tumor Formation,” Science 230, no. 4726 (November 8, 1985): 676–78. [http://www.ncbi.nlm.nih.gov/pubmed/2996144]
34. Macrophages and other inflammatory cells: Lisa M. Coussens and Zena Werb, “Inflammation and Cancer,” Nature 420, no. 6917 (December 19, 2002): 860–67. [http://dx.doi.org/10.1038/nature01322]
35. compared to bodily organs: Mina J. Bissell and Derek Radisky, “Putting Tumours in Context,” Nature Reviews Cancer 1, no. 1 (October 2001): 46–54. [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2975572]
CHAPTER 6 “How Heart Cells Embrace Their Fate”
1. an embryo is so much like a tumor: The complex process of implantation is described in Haibin Wang and Sudhansu K. Dey, “Roadmap to Embryo Implantation: Clues from Mouse Models,” Nature Reviews Genetics 7, no. 3 (March 1, 2006): 185–99. [http://www.nature.com/nrg/journal/v7/n3/abs/nrg1808.html] For some of the parallels with tumorigenesis see Michael J. Murray and Bruce A. Lessey, “Embryo Implantation and Tumor Metastasis: Common Pathways of Invasion and Angiogenesis,” Seminars in Reproductive Medicine 17, no. 3 (March 15, 2008): 275–90. [http://www.ncbi.nlm.nih.gov/pubmed/10797946]
2. enzymes erode the surface: L. A. Salamonsen, “Role of Proteases in Implantation,” Reviews of Reproduction 4, no. 1 (January 1999): 11–22. [http://www.ncbi.nlm.nih.gov/pubmed/10051098]
3. molecules help ensure a tight grip: Maaike S. M. van Mourik et al., “Embryonic Implantation: Cytokines, Adhesion Molecules, and Immune Cells in Establishing an Implantation Environment,” Journal of Leukocyte Biology 85, no. 1 (January 2009): 4–19.[http://www.ncbi.nlm.nih.gov/pubmed/18784344]
4. messages are sent to the immune system: Van Mourik et al., “Embryonic Implantation.”
5. begins stimulating angiogenesis: D. M. Sherer and O. Abulafia, “Angiogenesis During Implantation, and Placental and Early Embryonic Development,” Placenta 22, no. 1 (January 2001): 1–13. [http://www.ncbi.nlm.nih.gov/pubmed/11162347]
6. the more parallels they find: Melissa Marino, “In the Beginning: What Developmental Biology Can Teach About Cancer,” Lens online magazine, Vanderbilt Medical Center website, February 2007. [http://www.mc.vanderbilt.edu/lens/article/?id=170]
7. epithelial-mesenchymal transition: The seminal article is Jean Paul Thiery, “Epithelial-Mesenchymal Transitions in Tumour Progression,” Nature Reviews Cancer 2, no. 6 (June 2002): 442–54. [http://dx.doi.org/10.1038/nrc822] Good reviews include Yibin Kang and Joan Massagué, “Epithelial-Mesenchymal Transitions: Twist in Development and Metastasis,” Cell 118, no. 3 (August 6, 2004): 277–79; [http://www.ncbi.nlm.nih.gov/pubmed/15294153] Jonathan M. Lee et al., “The Epithelial-Mesenchymal Transition: New Insights in Signaling, Development, and Disease,” Journal of Cell Biology 172, no. 7 (March 27, 2006): 973–81; [http://www.ncbi.nlm.nih.gov/pubmed/16567498] Jing Yang and Robert A. Weinberg, “Epithelial-Mesenchymal Transition: At the Crossroads of Development and Tumor Metastasis,” Developmental Cell 14, no. 6 (June 2008): 818–29; [http://www.ncbi.nlm.nih.gov/pubmed/18539112] and Raghu Kalluri and Robert A. Weinberg, “The Basics of Epithelial-Mesenchymal Transition,” Journal of Clinical Investigation 119, no. 6 (June 1, 2009): 1420–28. [http://www.jci.org/articles/view/39104] For an account by some naysayers see David Tarin, Erik W. Thompson, and Donald F. Newgreen, “The Fallacy of Epithelial Mesenchymal Transition in Neoplasia,” Cancer Research 65, no. 14 (July 15, 2005): 5996–6001. [http://www.ncbi.nlm.nih.gov/pubmed/16024596] Both sides of the controversy are described in Heidi Ledford, “Cancer Theory Faces Doubts,” Nature 472, no. 7343 (April 21, 2011): 273. [http://www.ncbi.nlm.nih.gov/pubmed/21512545]
8. holding its annual meeting: Society for Developmental Biology Sixty-Ninth Annual Meeting, August 5–9, 2010, Albuquerque, NM. I also attended the Seventieth Annual Meeting, July 21–22, 2011, in Chicago. For a nice overview of developmental biology, see Sean B. Carroll, Endles
s Forms Most Beautiful: The New Science of Evo Devo (New York: Norton, 2006). The website of the Society for Developmental Biology [http://www.sdbonline.org] provides a portal to numerous resources like WormAtlas, with detailed and annotated maps of C. elegans, and FlyBrain, which covers the Drosophila nervous system.
9. “Organogenesis”: The proceedings of the Albuquerque conference are in Developmental Biology 344, no. 1 (2010): 391–542. [http://www.sciencedirect.com/science/journal/00121606/344/1]
10. wingless, frizzled, smoothened, patched, and disheveled: Though I have tried to be consistent in my own usage, I have not religiously followed the rules for when to render the names and symbols of genes in upper case or lower case or italics or roman. Apologies to the specialists who may find that distracting.
11. possible treatments for baldness: Andrzej Dlugosz, “The Hedgehog and the Hair Follicle: A Growing Relationship,” Journal of Clinical Investigation 104, no. 7 (October 1, 1999): 851–53. [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC408568]
12. “The quirky sense of humour”: Ken Maclean, “Humour of Gene Names Lost in Translation to Patients,” Nature 439, no. 7074 (January 19, 2006): 266. [http://dx.doi.org/10.1038/439266d]
13. It now goes by the less evocative name Zbtb7: Tom Simonite, “Pokemon Blocks Gene Name,” Nature 438, no. 7070 (December 14, 2005): 897. [http://www.nature.com/nature/journal/v438/n7070/full/438897a.html]
14. Since it was discovered in 1993: R. D. Riddle, C. Tabin, et al., “Sonic Hedgehog Mediates the Polarizing Activity of the ZPA,” Cell 75, no. 7 (December 31, 1993): 1401–16. [http://www.ncbi.nlm.nih.gov/pubmed/8269518]
The Cancer Chronicles Page 26