The Cancer Chronicles

by George Johnson

  46. in a leper skeleton from a medieval cemetery: Donald J. Ortner, Keith Manchester, and Frances Lee, “Metastatic Carcinoma in a Leper Skeleton from a Medieval Cemetery in Chichester, England,” International Journal of Osteoarchaeology 1, no. 2 (June 1, 1991): 91–98. [http://onlinelibrary.wiley.com/doi/10.1002/oa.1390010204/abstract]

  47. near the Tower of London: M. Melikian, “A Case of Metastatic Carcinoma from 18th Century London,” International Journal of Osteoarchaeology 16, no. 2 (March 1, 2006): 138–44. [http://onlinelibrary.wiley.com/doi/10.1002/oa.1390010204/abstract]

  48. excavated a 2,700-year-old burial mound: Details of the discovery are described on the website of the German Archaeological Institute: “Complete Excavation of the Kurgan Arzhan 2 including an Undisturbed Royal Grave (late 7th century B.C.).” [http://www.dainst.org/en/project/russian-federation-tuva-arzhan] More information is on the website of the State Hermitage Museum in St. Petersburg: “Restoration and Reconstruction of the Arzhan-2 Complex of Artifacts.” [http://www.hermitagemuseum.org/html_En/13/hm13_3_020.html] I described this and some other cases more briefly in “Trying to Estimate Cancer Rates in Ancient Times,” New York Times, December 27, 2010. [http://www.nytimes.com/2010/12/28/health/28cancer.html]

  49. his skeleton was infested with tumors: Michael Schultz et al., “Oldest Known Case of Metastasizing Prostate Carcinoma Diagnosed in the Skeleton of a 2,700-year-old Scythian King from Arzhan (Siberia, Russia),” International Journal of Cancer 121, no. 12 (December 15, 2007): 2591–95. [http://www.ncbi.nlm.nih.gov/pubmed/17918181]

  50. the partially cremated pelvis of a first-century Roman: G. Grévin, R. Lagier, and C. A. Baud, “Metastatic Carcinoma of Presumed Prostatic Origin in Cremated Bones from the First Century A.D.,” Virchows Archiv: An International Journal of Pathology 431, no. 3 (September 1997): 211–14. [http://www.ncbi.nlm.nih.gov/pubmed/9334843]

  51. a skeleton from a fourteenth-century graveyard: T. Anderson, J. Wakely, and A. Carter, “Medieval Example of Metastatic Carcinoma: A Dry Bone, Radiological, and SEM Study,” American Journal of Physical Anthropology 89, no. 3 (November 1992): 309–23. [http://onlinelibrary.wiley.com/doi/10.1002/ajpa.1330890305/abstract]

  52. osteoblastic … osteolytic: Waldron, “What Was the Prevalence?”

  53. show the strongest appetite: Tony Waldron, Palaeopathology (Cambridge: Cambridge University Press, 2009), 185.

  54. A middle-aged woman with osteolytic lesions: M. J. Allison et al., “Metastatic Tumor of Bone in a Tiahuanaco Female,” Bulletin of the New York Academy of Medicine 56, no. 6 (1980): 581–87. [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1808324]

  55. a Late Holocene hunter-gather: L. H. Luna et al., “A Case of Multiple Metastasis in Late Holocene Hunter-gatherers from the Argentine Pampean Region,” International Journal of Osteoarchaeology 18, no. 5 (November 14, 2007): 492–506. [http://onlinelibrary.wiley.com/doi/10.1002/oa.950/abstract]

  56. Like 90 percent of human cancers: “Cancer Overview,” Stanford School of Medicine Cancer Institute website. [http://cancer.stanford.edu/information/cancerOverview.html]

  57. For children … only a fraction of cancers are carcinomas: “Disease Information,” St. Jude Children’s Research Hospital website. [http://www.stjude.org/stjude/v/index.jsp?vgnextoid=393d061585f70110VgnVCM1000001e0215acRCRD]

  58. often spread first to the lung or liver: “Metastatic Cancer,” National Cancer Institute website, reviewed May 23, 2011. [http://www.cancer.gov/cancertopics/factsheet/Sites-Types/metastatic] Prostate cancer is drawn to bone, but it would probably have been less frequent when life spans were shorter.

  59. “swellings” and “eatings”: See, for example, Margaret M. Olszewski, “Concepts of Cancer from Antiquity to the Nineteenth Century,” University of Toronto Medical Journal 87, no. 3 (May 2010) [http://utmj.org/ojs/index.php/UTMJ/article/view/1252]; and Retsas, Palaeo-Oncology, 36.

  60. A rectal carcinoma in a 1,600-year-old mummy: A. Rosalie David and Michael R. Zimmerman, “Cancer: An Old Disease, a New Disease or Something in Between?” Nature Reviews Cancer 10, no. 10 (October 2010): 728–33. [http://www.nature.com/nrc/journal/v10/n10/full/nrc2914.html]

  61. diagnosed with bladder cancer: Michael R. Zimmerman and Arthur C. Aufderheide, “Seven Mummies of the Dakhleh Oasis, Egypt: Seventeen Diagnoses,” Paleopathology Newsletter 150 (June 2010): 16–23.

  62. on the face of a Chilean child: David and Zimmerman, “Cancer: An Old Disease, a New Disease?”

  63. nine pre-Columbian Incan mummies: Oscar B. Urteaga and George T. Pack, “On the Antiquity of Melanoma,” Cancer 19, no. 5 (May 1, 1966): 607–10. [http://www.ncbi.nlm.nih.gov/pubmed/5326247]

  64. To prepare a pharaoh: Leonard Weiss, “Observations on the Antiquity of Cancer and Metastasis,” Cancer and Metastasis Reviews 19, nos. 3–4 (December 2000): 193–204. [http://www.springerlink.com/content/h2205q07rm735720/abstract]

  65. embalmed tumors can survive: M. R. Zimmerman, “An Experimental Study of Mummification Pertinent to the Antiquity of Cancer,” Cancer 40 (1977): 1358–62. [http://www.ncbi.nlm.nih.gov/pubmed/902245] In an experiment, a liver taken from a patient with metastatic carcinoma was dried in an oven and then rehydrated. Zimmerman observed that “the features of cancer (large, dark staining and highly variable nuclei and invasion of surrounding tissue) are well preserved by mummification and that mummified tumors are actually better preserved than normal tissue.” E-mail to author, November 11, 2010.

  66. Ferrante I of Aragon: The king was also obese and his bones were infused with lead and zinc. See Gino Fornaciari et al., “K-ras Mutation in the Tumour of King Ferrante I of Aragon (1431–94) and Environmental Mutagens at the Aragonese Court of Naples,” International Journal of Osteoarchaeology 9, no. 5 (October 6, 1999): 302–6; [http://onlinelibrary.wiley.com/doi/10.1002/(SICI)1099-1212(199909/10)9:5<302::AID-OA487>3.0.CO;2-V/abstract]; Antonio Marchetti, Gino Fornaciari, et al., “K-RAS Mutation in the Tumour of Ferrante I of Aragon, King of Naples,” Lancet 347, no. 9010 (May 1996): 1272 [http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(96)90798-9/fulltext]; and Laura Ottini, Gino Fornaciari, et al., “Gene-Environment Interactions in the Pre-Industrial Era: The Cancer of King Ferrante I of Aragon (1431–1494),” Human Pathology 42, no. 3 (March 2011): 332–39. [http://www.ncbi.nlm.nih.gov/pubmed/21111451]

  67. counted about two hundred suspected cancer sightings: I started with 176 examples Strouhal had tabulated in what he called the Old World (reference in A. Sefcáková, E. Strouhal, et al., “Case of Metastatic Carcinoma from End of the 8th–early 9th Century Slovakia,” American Journal of Physical Anthropology 116, no. 3 [November 2001]: 216–29) [http://www.ncbi.nlm.nih.gov/pubmed/11596001] and then added in New World cases and cases found since the paper was published.

  68. stumbled on by chance: Strouhal comments on this in “Tumors in the Remains of Ancient Egyptians.”

  69. taphonomic changes: Waldron, Palaeopathology, 21–23; Weiss, “Observations on the Antiquity of Cancer and Metastasis”; and E. Strouhal, “Malignant Tumors in the Old World,” Paleopathology Newsletter no. 85, suppl. (1994): 1–6.

  70. pseudopathology: Aufderheide and Rodriguez-Martin, Cambridge Encyclopedia of Human Paleopathology, 11–18.

  71. significantly underreported: In Diseases in Antiquity, Brothwell speculates that “the scarcity of tumours has been overemphasized in the past—a fact which in itself may have depressed some detailed searching.” See his chapter “The Evidence for Neoplasms,” 320–45. Also see Waldron, “What Was the Prevalence?”

  72. more likely to appear in certain bones: Waldron, Palaeopathology, 185.

  73. Hoping to cut through the uncertainty: Waldron, “What Was the Prevalence?”

  74. between 0 and 2 percent for males and 4 and 7 percent for females: See figure 1 of Waldron, “What Was the Prevalence?” The numbers were higher for women because of uterine and breast cancer. In the next century cancer in men would come to dominate because of cigarettes and lung cancer.

  75. The next
step: Andreas G. Nerlich et al., “Malignant Tumors in Two Ancient Populations: An Approach to Historical Tumor Epidemiology,” Oncology Reports 16, no. 1 (July 2006): 197–202. [http://www.ncbi.nlm.nih.gov/pubmed/16786146]

  76. an article that had just appeared: David and Zimmerman, “Cancer: An Old Disease, a New Disease?”

  77. In a news release from her university: “Scientists Suggest that Cancer Is Man-made,” University of Manchester website, October 14, 2010. [http://www.manchester.ac.uk/aboutus/news/display/?id=6243]

  78. some take the number at face value: See, for example, Luigi L. Capasso, “Antiquity of Cancer,” International Journal of Cancer 113, no. 1 (January 1, 2005): 2–13 [http://www.ncbi.nlm.nih.gov/pubmed/1538951]; and M. S. Micozzi, “Diseases in Antiquity: The Case of Cancer,” Archives of Pathology and Laboratory Medicine 115 (1991): 838–44. [http://www.ncbi.nlm.nih.gov/pubmed/1863198]

  79. the total number of ancient and prehistoric skeletons: The anthropologists I asked were Anne L. Grauer, president of the Paleopathology Association and an anthropologist at Loyola University in Chicago, Heather J. H. Edgar, curator of human osteology at the Maxwell Museum of Anthropology at the University of New Mexico, and Tim D. White, Professor of Integrative Biology at the University of California, Berkeley.

  80. A demographer … made a rough calculation: Carl Haub, “How Many People Have Ever Lived on Earth?” October 2011, Population Reference Bureau website. [http://www.prb.org/Articles/2002/HowManyPeopleHaveEverLivedonEarth.aspx]

  CHAPTER 4 Invasion of the Body Snatchers

  1. “rheumatism and debility”: T. R. Ashworth, “A Case of Cancer in Which Cells Similar to Those in the Tumours Were Seen in the Blood After Death,” Australian Medical Journal 14 (1869): 146–47.

  2. secreting “morbid juices”: L. Weiss, “Concepts of Metastasis,” Cancer and Metastasis Reviews 19 (2000): 219–34, which is part 3 of a longer piece, “Metastasis of Cancer: A Conceptual History from Antiquity to the 1990s,” 193–400. [http://www.ncbi.nlm.nih.gov/pubmed/11394186] I also relied on two other articles by Weiss in the same issue: “Observations on the Antiquity of Cancer and Metastasis” (193–204) and “Early Concepts of Cancer” (205–17). Other sources on the history of the cellular idea of cancer include James Stuart Olson, The History of Cancer: An Annotated Bibliography (New York: Greenwood Press, 1989); Erwin H. Ackerknecht, “Historical Notes on Cancer,” Medical History 2, no. 2 (April 1958): 114–19 [http://www.ncbi.nlm.nih.gov/pubmed/11394186]; Margaret M. Olszewski, “Concepts of Cancer from Antiquity to the Nineteenth Century,” University of Toronto Medical Journal 87, no. 3 (May 2010); and W. I. B. Onuigbo, “The Paradox of Virchow’s Views on Cancer Metastasis,” Bulletin of the History of Medicine 34 (1962): 444–49. [http://www.ncbi.nlm.nih.gov/pubmed/13940181] Another valuable resource was Jacob Wolff, The Science of Cancerous Disease from Earliest Times to the Present, first published in 1907. It was translated from German by Barbara Ayoub and reissued in 1989 by Science History Publications and the National Library of Medicine.

  3. “metastatic affections”: Weiss, “Early Concepts of Cancer.”

  4. an idea that was carried by Galen: Ackerknecht, “Historical Notes.”

  5. Descartes saw a connection: Ackerknecht, “Historical Notes.”

  6. A Parisian surgeon: Weiss, “Concepts of Metastasis.”

  7. traveling along the lymph vessel walls: Weiss, “Concepts of Metastasis.”

  8. Even the nervous system: Weiss, “Concepts of Metastasis.”

  9. leprosy and elephantiasis: Ackerknecht, “Historical Notes.”

  10. “cancer juice”: Ackerknecht, “Historical Notes.”

  11. not sharp enough to show: Wolff, Science of Cancerous Disease, 101–3.

  12. a book published in 1838: There is an English version translated by Charles West as On the Nature and Structural Characteristics of Cancer, and Those Morbid Growths Which May Be Confounded with It (London: Sherwood, Gilbert, and Piper, 1840). For an excerpt see Johannes Müller, “On the Nature and Structural Characteristics of Cancer: General Observations on the Minute Structure of Morbid Growths,” CA: A Cancer Journal for Clinicians 23, no. 5 (December 30, 2008): 307–12. [http://onlinelibrary.wiley.com/doi/10.3322/canjclin.23.5.307/abstract]

  13. from a primitive fluid called blastema: Müller’s ideas are summarized in Wolff, Science of Cancerous Disease, 108; and Olszewski, “Concepts of Cancer.”

  14. Virchow, took the next step: Ackerknecht, “Historical Notes.”

  15. “a dissemination of cells”: Onuigbo, “The Paradox of Virchow’s Views.”

  16. all cancer arose from connective tissue: Ackerknecht, “Historical Notes.”

  17. Thiersch helped discredit that idea: Ackerknecht, “Historical Notes.”

  18. “Cancer is incurable”: Quoted in Weiss, “Early Concepts of Cancer.”

  19. still not entirely clear today: Robert A. Weinberg, The Biology of Cancer (New York: Garland Science, 2007), 593–94.

  20. encompass 3,914 pages: Wolff, Science of Cancerous Disease, ix.

  21. “may or may not wish to compare”: The introduction is by the medical historian Saul Jarcho, MD.

  22. “When a plant goes to seed”: S. Paget, “The Distribution of Secondary Growths in Cancer of the Breast,” Lancet 133, no. 3421 (1889): 571–73. It was republished as “Stephen Paget’s Paper Reproduced from The Lancet, 1889,” Cancer and Metastasis Reviews 8, no. 2 (1989): 98–101. [http://www.springerlink.com/content/xmm1773487341l71]

  23. it would soon be swamped: Weinberg, Biology of Cancer, 636.

  24. head straight for the brain: “Metastatic Brain Tumor,” published online by the National Library of Medicine, Medline Plus website. [http://www.nlm.nih.gov/medlineplus/ency/article/000769.htm]

  25. Ian Hart and Isaiah Fidler: Their paper is “Role of Organ Selectivity in the Determination of Metastatic Patterns of the B16 Melanoma,” Cancer Research 40 (1980): 2281–87. [http://cancerres.aacrjournals.org/content/40/7/228] Also see Isaiah J. Fidler, “The Pathogenesis of Cancer Metastasis: The ‘Seed and Soil’ Hypothesis Revisited,” Nature Reviews Cancer 3, no. 6 (June 2003): 453–58. [http://www.nature.com/nrc/journal/v3/n6/abs/nrc1098.html]

  26. A video I came across: “Overview of Metastasis,” published online by CancerQuest, Winship Cancer Institute website, Emory University. [http://www.cancerquest.org/metastasis-overview.html]

  27. The process is called anoikis: Lance A. Liotta and Elise Kohn. “Anoikis: Cancer and the Homeless Cell,” Nature 430, no. 7003 (August 26, 2004): 973–74. [http://www.nature.com/nature/journal/v430/n7003/full/430973a.html]

  28. most will perish immediately: For a fascinating account of the intricacies of metastasis, see Weinberg, Biology of Cancer, chapter 14. I also referred to Ann F. Chambers, Alan C. Groom, and Ian C. MacDonald, “Metastasis: Dissemination and Growth of Cancer Cells in Metastatic Sites,” Nature Reviews Cancer 2, no. 8 (August 1, 2002): 563–72 [http://www.nature.com/nrc/journal/v2/n8/abs/nrc865.html]; and Christine L. Chaffer and Robert A. Weinberg, “A Perspective on Cancer Cell Metastasis,” Science 331, no. 6024 (March 25, 2011): 1559–64. [http://www.sciencemag.org/content/331/6024/1559]

  29. jettison enough of their cytoplasm: Weinberg, Biology of Cancer, 593–94. He suggests a more likely explanation is that cancer cells can avoid the capillary trap by passing instead through arterial-venous shunts.

  30. researchers found that after twenty-four hours: For a review see Fidler, “Pathogenesis of Cancer Metastasis.”

  31. cancer in one breast: Weinberg, Biology of Cancer, 636, sidebar 14.8.

  32. a molecular “zip code” identifying the organ: Weinberg, Biology of Can- cer, 637.

  33. priming them for survival: Andy J. Minn, Joan Massagué, et al., “Genes That Mediate Breast Cancer Metastasis to Lung,” Nature 436, no. 7050 (July 28, 2005): 518–24 [http://www.ncbi.nlm.nih.gov/pubmed/16049480]; and Paula D. Bos, J. Massagué, et al., “Genes That Mediate Breast Cancer Metastasis to the Brain,” Nature 459, no. 7249 (June 18, 2009):
1005–9. [http://www.ncbi.nlm.nih.gov/pubmed/19421193]

  34. a premetastatic niche: Rosandra N. Kaplan, Shahin Rafii, and David Lyden, “Preparing the ‘Soil’: The Premetastatic Niche,” Cancer Research 66, no. 23 (December 1, 2006): 11089–93. [http://cancerres.aacrjournals.org/content/66/23/11089]

  35. the travelers can bring their own soil: Dan G. Duda et al., “Malignant Cells Facilitate Lung Metastasis by Bringing Their Own Soil,” Proceedings of the National Academy of Sciences 107, no. 50 (December 14, 2010): 21677–82. [http://www.pnas.org/content/107/50/21677.abstract]

  36. exchange signals with the natives: The process is described in the general references on metastasis listed above.

  37. rejoin the battle at home: Larry Norton and Joan Massagué, “Is Cancer a Disease of Self-seeding?” Nature Medicine 12, no. 8 (August 2006): 875–78 [http://www.ncbi.nlm.nih.gov/pubmed/16892025]; Mi-Young Kim, Joan Massagué, et al., “Tumor Self-seeding by Circulating Cancer Cells,” Cell 139, no. 7 (December 24, 2009): 1315–26 [http://www.ncbi.nlm.nih.gov/pubmed/20064377]; and Elizabeth Comen, Larry Norton, and Joan Massagué, “Clinical Implications of Cancer Self-seeding,” Nature Reviews Clinical Oncology 8, no. 6 (June 2011): 369–77. [http://www.ncbi.nlm.nih.gov/pubmed/21522121]

  38. the ability to initiate angiogenesis: J. Folkman et al., “Isolation of a Tumor Factor Responsible for Angiogenesis,” The Journal of Experimental Medicine 133, no. 2 (February 1, 1971): 275–88. [http://www.ncbi.nlm.nih.gov/pubmed/4332371]

  39. creating connections to the lymphatic system: Viviane Mumprecht and Michael Detmar, “Lymphangiogenesis and Cancer Metastasis,” Journal of Cellular and Molecular Medicine 13, no. 8A (August 2009): 1405–16. [http://www.ncbi.nlm.nih.gov/pubmed/19583813]

  40. signals to a nearby lymph node: Satoshi Hirakawa et al., “VEGF-C-induced Lymphangiogenesis in Sentinel Lymph Nodes Promotes Tumor Metastasis to Distant Sites,” Blood 109, no. 3 (February 1, 2007): 1010–17. [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1785149]

  41. survival rate can be as high as 90 percent: “Endometrial (Uterine) Cancer: Survival by Stage” [http://www.cancer.org/Cancer/EndometrialCancer/DetailedGuide/endometrial-uterine-cancer-survival-rates] and “How Is Endometrial Cancer Staged?” [http://www.cancer.org/Cancer/EndometrialCancer/DetailedGuide/endometrial-uterine-cancer-staging] Both are on the American Cancer Society website, last revised July 25, 2012.