21. the five-year survival rate was as high as 80 percent: “Medulloblastoma,” 17.
22. “I met one kid, a teenager”: Curran, “Oncology as a Team Sport.”
23. research from other labs: For an overview see Ken Garber, “Hedgehog Drugs Begin to Show Results,” Journal of the National Cancer Institute 100, no. 10 (May 21, 2008): 692–97. [http://jnci.oxfordjournals.org/content/100/10/692.extract]
24. the story of the cyclopean lambs: This is told in chapter 6 of this book.
25. a meeting on brain genetics and development: Genetic Basis of Brain Development and Dysfunction, March 18–23, 2000, Sagebrush Inn and Conference Center, Taos, New Mexico. [http://www.keystonesymposia.org/index.cfm?e=Web.Meeting.Program&MeetingID=514] The authority on hedgehog signaling was Andrew McMahon at Harvard University.
26. Curran went on to show: Justyna T. Romer, T. Curran, et al., “Suppression of the Shh Pathway Using a Small Molecule Inhibitor,” Cancer Cell 6, no. 3 (September 2004): 229–40. [http://www.sciencedirect.com/science/article/pii/S1535610804002417]
27. inhibited bone development: Garber, “Hedgehog Drugs Begin to Show Results.”
28. there were signs that the drug … was safe: “Experimental Targeted Therapy Shows Early Promise Against Medulloblastomas,” St. Jude Children’s Research Hospital website, June 5, 2010. [http://multivu.prnewswire.com/mnr/stjude/44444]
29. approved for basal cell carcinoma: “FDA Approval for Vismodegib,” National Cancer Institute website. [http://www.cancer.gov/cancertopics/druginfo/fda-vismodegib]
30. “forward looking”: Emmy Wang, senior manager, corporate relations, Genentech, e-mail to author on behalf of Fred de Sauvage, March 2, 2012.
31. a body called the United States Adopted Names Council: For a deciphering of generic drug names see “USAN Stem List,” American Medical Association website. [http://www.ama-assn.org/resources/doc/usan/stem-list-cumulative.pdf]
32. described the latest findings: José Baselga, keynote (untitled), Translational Cancer Research Workshop, Boston, October 17, 2010.
33. “super Herceptin” or trastuzumab emtansine: Ion Niculescu-Duvaz, “Trastuzumab Emtansine, an Antibody-drug Conjugate for the Treatment of HER2+ Metastatic Breast Cancer,” Current Opinion in Molecular Therapeutics 12, no. 3 (June 2010): 350–60. [http://www.ncbi.nlm.nih.gov/pubmed/20521224]
34. drug called pertuzumab: Cormac Sheridan, “Pertuzumab to Bolster Roche/Genentech’s Breast Cancer Franchise?” Nature Biotechnology 29, no. 10 (October 13, 2011): 856–58. [http://www.nature.com/nbt/journal/v29/n10/full/nbt1011-856b.html]
35. pertuzumab became Perjeta: “FDA Approval for Pertuzumab,” National Cancer Institute website, June 11, 2012. [http://www.cancer.gov/cancertopics/druginfo/fda-pertuzumab]
36. patients were outraged: Robert Weisman, “Limits on Test Drugs Add to Patients’ Ordeals,” Boston Globe, January 5, 2011. [http://www.boston.com/business/healthcare/articles/2011/01/05/testing_rules_force_patients_to_wait_for_new_drugs]
37. the agency insisted on waiting: Martin de Sa’Pinto and Katie Reid, “FDA Puts Brakes on Roche, ImmunoGen Cancer Drug,” Reuters, August 27, 2010. [http://www.reuters.com/article/2010/08/27/roche-idUSLDE67Q03620100827]
38. a rally outside Boston City Hall: The date was December 6, 2011.
39. “reduced the risk of cancer worsening”: Media release, June 3, 2012, Roche website. [http://www.roche.com/media/media_releases/med-cor-2012-06-03b.htm] Also see Lisa Hutchinson, “From ASCO—Breast Cancer: EMILIA Trial Offers Hope,” Nature Reviews Clinical Oncology 9, no. 8 (August 1, 2012): 430. It was approved February 22, 2013, by the FDA and is sold as Kadcyla.
40. “smoothes and tightens the skin”: Barbara Ehrenreich, “Welcome to Cancerland,” Harper’s Magazine, November 2001. [http://www.barbaraehrenreich.com/cancerland.htm] Also see Gayle A. Sulik, Pink Ribbon Blues: How Breast Cancer Culture Undermines Women’s Health, (New York: Oxford University Press, 2011).
41. how many lives that saves: For more on the controversy over breast cancer treatment see Robert A. Aronowitz, Unnatural History: Breast Cancer and American Society (Cambridge: Cambridge University Press, 2007); and David Plotkin, “Good News and Bad News About Breast Cancer,” The Atlantic, June 1998. [http://www.theatlantic.com/magazine/archive/1998/06/good-news-and-bad-news-about-breast-cancer/5504]
42. A recent epidemiological study of 600,000 women: P. C. Gøtzsche and M. Nielsen, “Screening for Breast Cancer with Mammography,” The Cochrane Library 4 (2009). A summary was published on the Cochrane website April 13, 2011. [http://summaries.cochrane.org/CD001877/screening-for-breast-cancer-with-mammography]
43. a disturbing number: Timothy J. Wilt et al., “Radical Prostatectomy Versus Observation for Localized Prostate Cancer,” New England Journal of Medicine 367, no. 3 (2012): 203–13. [http://www.nejm.org/action/showCitFormats?doi=10.1056%2FNEJMoa1113162] Also see G. Sandblom et al., “Randomised Prostate Cancer Screening Trial: 20 Year Follow-up,” BMJ: British Medical Journal 342 (March 31, 2011): d1539. [http://www.bmj.com/content/342/bmj.d1539]
44. About 70 percent of men in their seventies: For a review of the autopsy studies see Richard M. Martin, “Commentary: Prostate Cancer Is Omnipresent, but Should We Screen for It?” International Journal of Epidemiology 36, no. 2 (April 1, 2007): 278–81. [http://ije.oxfordjournals.org/content/36/2/278.extract]
45. Urologists offer free tickets: The examples are from Gary Schwitzer, “Cheerleading, Shibboleths and Uncertainty,” a presentation on April 23, 2012, Science Writing in the Age of Denial, University of Wisconsin, Madison, WI. The urinal example was provided to Schwitzer by Ivan Oransky, the executive editor of Reuters Health.
46. one of “the best and brightest”: Tom Junod, “Franziska Michor Is the Isaac Newton of Biology,” Esquire, November 20, 2007. [http://www.esquire.com/features/michor1207]
47. uncovered some of the early clues: See, for example, J. C. Fisher, “Multiple-Mutation Theory of Carcinogenesis,” Nature 181 (March 1, 1958): 651–52 [http://www.nature.com/nature/journal/v181/n4609/abs/181651b0.html]; P. Armitage and R. Doll, “The Age Distribution of Cancer and a Multi-stage Theory of Carcinogenesis,” British Journal of Cancer 8 (1954): 1–12 [http://www.nature.com/bjc/journal/v91/n12/full/6602297a.html]; and C. O. Nordling, “A New Theory on the Cancer-inducing Mechanism,” British Journal of Cancer 7, no. 1 (March 1953): 68–72. [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2007872]
48. “hitchhiker” or “passenger” mutations: Ondrej Podlaha, Franziska Michor, et al., “Evolution of the Cancer Genome,” Trends in Genetics 28, no. 4 (April 1, 2012): 155–63. [http://www.cell.com/trends/genetics/abstract/S0168-9525(12)00012-1]
49. the order in which the mutations occur: Camille Stephan-Otto Attolini, Franziska Michor, et al., “A Mathematical Framework to Determine the Temporal Sequence of Somatic Genetic Events in Cancer,” Proceedings of the National Academy of Sciences 107, no. 41 (October 12, 2010): 17604–9. [http://www.ncbi.nlm.nih.gov/pubmed/20864632] [full text: http://www.pnas.org/content/107/41/17604.full.pdf]
50. so quickly overcome the obstacles: Podlaha, Michor, et al., “Evolution of the Cancer Genome.”
51. it sometimes pays for adversaries to cooperate: The classic paper is R. Axelrod and W. D. Hamilton, “The Evolution of Cooperation,” Science 211, no. 4489 (March 27, 1981): 1390–96. [http://www.ncbi.nlm.nih.gov/pubmed/7466396]
52. has suggested how that might apply: Robert Axelrod, David E. Axelrod, and Kenneth J Pienta, “Evolution of Cooperation Among Tumor Cells,” Proceedings of the National Academy of Sciences 103, no. 36 (September 5, 2006): 13474–79. [http://www.pnas.org/content/103/36/13474]
53. “Cancer isn’t getting smarter”: The Stand Up to Cancer presentation was at the 2011 Annual Meeting of the American Association for Cancer Research, Orlando, FL, April 2–6. The scientist quoted is Angelique Whitehurst.
54. “an ugly mass, rounded and bulging”: David Quammen, “Contagious Cancer: The Evolution of a Killer,” Harper’s Magazine, April 2008.
[http://harpers.org/archive/2008/04/0081988]
55. scientists have since traced the origin: Elizabeth P. Murchison et al., “Genome Sequencing and Analysis of the Tasmanian Devil and Its Transmissible Cancer,” Cell 148, no. 4 (February 17, 2012): 780–91. [http://www.cell.com/retrieve/pii/S0092867412000815]
56. “the immortal devil”: Ewen Callaway, “Field Narrows in Hunt for Devil Tumour Genes,” Nature, News and Comment, published online February 16, 2012. [http://www.nature.com/doifinder/10.1038/nature.2012.10046]
57. spread between hamsters by mosquitoes: W. G. Banfield et al., “Mosquito Transmission of a Reticulum Cell Sarcoma of Hamsters,” Science 148, no. 3674 (May 28, 1965): 1239–40. [http://www.sciencemag.org/content/148/3674/1239.abstract?sid=16f27225-5ed2-4221-a2cc-fe070ff430c0]
CHAPTER 13 Beware the Echthroi
1. “See if aspirin cures the headache”: My trip to Sandia Crest and the situation in Santa Fe are described in “On Top of Microwave Mountain,” Slate, April 21, 2010. [http://www.slate.com/articles/health_and_science/science/2010/04/on_top_of_microwave_mountain.html]
2. a book about mass hysteria: Elaine Showalter, Hystories: Hysterical Epidemics and Modern Media (New York: Columbia University Press, 1997).
3. the threshold set by the Federal Communications Commission: Federal Communications Commission, “Evaluating Compliance with FCC Guidelines for Human Exposure to Radiofrequency Electromagnetic Fields,” OET Bulletin 65 (August 1997): 67. [http://transition.fcc.gov/Bureaus/Engineering_Technology/Documents/bulletins/oet65/oet65.pdf] See part B of table 1, “Limits for Maximum Permissible Exposure (MPE),” for 1,500–100,000 Mhz. (The occupational limit is 5mW/cm2 for six minutes.) For more information see the FCC’s “Questions and Answers About Biological Effects and Potential Hazards of Radiofrequency Electromagnetic Fields,” OET Bulletin 56, 4th ed. (August 1999). [http://transition.fcc.gov/Bureaus/Engineering_Technology/Documents/bulletins/oet56/oet56e4.pdf] Cell phone exposure is also measured in watts per kilogram—the rate of radio frequency energy absorption by the body.
4. about 100 milliwatts per square centimeter: “Calculating the Energy from Sunlight over a 12–Hour Period,” Math & Science Resources, National Aeronautics and Space Administration website. [http://www.grc.nasa.gov/WWW/k-12/Numbers/Math/Mathematical_Thinking/sun12.htm]
5. contradictory and inconclusive: For a summary and general information about wireless technologies and health, see Rfcom, a website maintained by the McLaughlin Centre for Population Health Risk Assessment at the University of Ottawa. [http://www.rfcom.ca]
6. A review by the World Health Organization: “Electromagnetic Fields, Summary of Health Effects,” WHO website. [http://www.who.int/peh-emf/about/WhatisEMF/en/index1.html] Another good source is “Cell Phones and Cancer Risk” on the National Cancer Institute website. [http://www.cancer.gov/cancertopics/factsheet/Risk/cellphones]
7. has remained extremely low: See table 1.4 of the SEER statistics, N. Howlader et al., eds., “SEER Cancer Statistics Review,” 1975–2009 (Vintage 2009 Populations), National Cancer Institute, Bethesda, MD, based on November 2011 SEER data submission, posted to the SEER website, 2012. [http://seer.cancer.gov/csr/1975_2009_pops09]
8. slightly but steadily decreasing: N. Howlader et al., eds., “SEER Cancer Statistics Review,” table 1.7.
9. The most ambitious of these efforts: “The Interphone Study,” International Agency for Research on Cancer, World Health Organization, IARC website. [http://interphone.iarc.fr]
10. No relationship was found: “IARC Report to the Union for International Cancer Control (UICC) on the Interphone Study,” October 3, 2011, IARC website. [http://interphone.iarc.fr/UICC_Report_Final_03102011.pdf]
11. odds of being diagnosed with the cancer: This was a hard number to come up with. The statistics available online from SEER don’t break down brain tumors by type, but the agency made the calculation at my request. (E-mail to author from Rick Borchelt, NCI Media Relations, July 12, 2012.) For a somewhat lower estimate, see table 1 of Judith A. Schwartzbaum et al., “Epidemiology and Molecular Pathology of Glioma,” Nature Clinical Practice Neurology 2, no. 9 (2006): 494–503. [http://www.nature.com/nrneurol/journal/v2/n9/full/ncpneuro0289.html] Adding the incidence rates of the different kinds of glioma comes to 0.0049. The article also estimates that 77 percent of primary malignant brain tumors are gliomas. Multiplying SEER’s incidence rate for all gliomas, 0.0061, by 0.77 yields a slightly different value, 0.0047.
12. a later study by the National Cancer Institute: M. P. Little et al., “Mobile Phone Use and Glioma Risk: Comparison of Epidemiological Study Results with Incidence Trends in the United States,” BMJ: British Medical Journal 344 (March 8, 2012): e1147. [http://www.bmj.com/content/344/bmj.e1147]
13. to add microwaves: “IARC Classifies Radiofrequency Electromagnetic Fields as Possibly Carcinogenic to Humans,” May 31, 2011, IARC website. [http://www.iarc.fr/en/media-centre/pr/2011/pdfs/pr208_E.pdf] The IARC classifications are described on the agency’s website, last updated March 27, 2012. [http://monographs.iarc.fr/ENG/Classification/index.php
14. COSMOS: Joachim Schüz et al., “An International Prospective Cohort Study of Mobile Phone Users and Health (Cosmos): Design Considerations and Enrollment,” Cancer Epidemiology 35, no. 1 (February 2011): 37–43. [http://www.ncbi.nlm.nih.gov/pubmed/20810339]
15. suggested to widespread disbelief: The original study on power lines and cancer is Nancy Wertheimer and Ed Leeper, “Electrical Wiring Configurations and Childhood Cancer,” American Journal of Epidemiology 109, no. 3 (March 1, 1979): 273–84. [http://aje.oxfordjournals.org/content/109/3/273.abstract]
16. Robert Weinberg once estimated: Over a lifetime a human body makes on the order of 1016 cells. Divide that by the number of seconds in an 80-year life span, or 2.5 × 109, to get 4 × 106. Robert Weinberg, e-mail to author, November 8, 2010. In Biology of Cancer, page 43, he gives an order of magnitude estimate of 10 million.
17. we all would eventually get cancer: Interview with Robert Weinberg, August 18, 2010, Whitehead Institute, Boston, MA.
18. cancer is here “on purpose”: Interview with Robert Austin, October 21, 2010, Princeton University. He expanded on this idea at the first workshop organized by the National Cancer Institute’s Physical Sciences in Oncology program, “Integrating and Leveraging the Physical Sciences to Open a New Frontier in Oncology,” February 26–28, 2008, Arlington, VA. [http://physics.cancer.gov/ps1/pdf/Physical_Oncology_Meeting_Report_PS1_508.pdf]
19. Maybe … the cells in an organism do the same thing: Guillaume Lambert, Robert H. Austin, et al., “An Analogy Between the Evolution of Drug Resistance in Bacterial Communities and Malignant Tissues,” Nature Reviews Cancer 11, no. 5 (April 21, 2011): 375–82. [http://www.nature.com/nrc/journal/v11/n5/full/nrc3039.html]
20. an attempt to break the stalemate: The program is called Physical Sciences in Oncology. See Franziska Michor et al., “What Does Physics Have to Do with Cancer?” Nature Reviews Cancer 11, no. 9 (August 18, 2011): 657–70; [http://www.nature.com/nrc/journal/v11/n9/abs/nrc3092.html] and Paul Davies, “Rethinking Cancer,” Physics World (June 2010): 28–33. [http://cancer-insights.asu.edu/wp-content/uploads/2010/01/Physics-World-June-20101.pdf]
21. studying the mechanical forces: Denis Wirtz, Konstantinos Konstantopoulos, and Peter C. Searson, “The Physics of Cancer: The Role of Physical Interactions and Mechanical Forces in Metastasis,” Nature Reviews Cancer 11, no. 7 (June 24, 2011): 512–22. [http://www.nature.com/nrc/journal/v11/n7/abs/nrc3080.html]
22. a different level of abstraction: This was the subject of the Third Physical Sciences in Oncology Workshop, “The Coding, Decoding, Transfer, and Translation of Information in Cancer,” October 29–31, 2008, Arlington, VA.
23. cells can be thought of as oscillators: Donald Coffey, First Physical Sciences in Oncology Workshop, “Integrating and Leveraging the Physical Sciences.”
24. radio frequency waves to kill cancer cells: Mustafa Raoof and Steven A. Curley, “Non-Invasive Radi
ofrequency-Induced Targeted Hyperthermia for the Treatment of Hepatocellular Carcinoma,” International Journal of Hepatology 2011 (2011): 1–6. [http://www.hindawi.com/journals/ijhep/2011/676957]
25. an “ancient genetic toolkit”: Paul Davies, “Cancer: The Beat of an Ancient Drum?” The Guardian, April 25, 2011. [http://www.guardian.co.uk/commentisfree/2011/apr/25/cancer-evolution-ancient-toolkit-genes] For a fuller description of the hypothesis, see P. C. W. Davies and C. H. Lineweaver, “Cancer Tumors as Metazoa 1.0: Tapping Genes of Ancient Ancestors,” Physical Biology 8, no. 1 (February 1, 2011): 015001.
26. detailed computer simulations: The USC program, like the others, is described on the National Cancer Institute’s Physical Sciences in Oncology website. [http://physics.cancer.gov/centers/adv_usc.asp]
27. a Tinkertoy computer: A. K. Dewdney, “A Tinkertoy Computer That Plays Tic-tac-toe,” Scientific American 261, no. 4 (October 1989): 120–23.
28. a giant clock: Described on the Long Now Foundation website. [http://longnow.org]
29. told an audience of oncologists: Coffey, “Integrating and Leveraging the Physical Sciences.”
30. another of his ambitious machines: Described on the Applied Proteomics website. [http://www.appliedproteomics.com]
31. concentrating on the proteome: Interviews with Daniel Hillis, November 26, 2010, and David Agus, November 29, 2010, Los Angeles.
32. working for years on mapping the proteome: See, for example, Bonnie S. Watson et al., “Mapping the Proteome of Barrel Medic (Medicago Truncatula),” Plant Physiology 131, no. 3 (March 2003): 1104–23. [http://www.ncbi.nlm.nih.gov/pubmed/12644662]
33. continually announcing new discoveries: See, for example, “Comprehensive Molecular Portraits of Human Breast Tumours,” published online in Nature (September 23, 2012). [http://dx.doi.org/10.1038/nature11412]
34. “Ten Crazy Ideas About Cancer”: Seminar at Arizona State University, September 8, 2011. A summary and video are on ASU’s Center for the Convergence of Physical Science and Cancer Biology website. [http://cancer-insights.asu.edu/2011/08/1458]
The Cancer Chronicles Page 32