123 "In about three weeks lungs previously riddled with": Giulio D'Angio, "Pediatric Oncology Refracted through the Prism of Wilms' Tumor: A Discourse," Journal of Urology 164 (2000): 2073-77.
124 Sonja Goldstein's recollections: Jeremiah Goldstein, "Preface to My Mother's Diary," Journal of Pediatric Hematology/Oncology 30, no. 7 (2008): 481-504.
"The butcher shop"
128 Randomised screening trials are bothersome: H. J. de Koning, "Mammographic Screening: Evidence from Randomised Controlled Trials," Annals of Oncology 14 (2003): 1185-89.
128 The best [doctors] seem to have a sixth sense: Michael LaCombe, "What Is Internal Medicine?" Annals of Internal Medicine 118, no. 5 (1993): 384-88.
128 Emil Freireich and Emil Frei: John Laszlo, The Cure of Childhood Leukemia: Into the Age of Miracles (New Brunswick, NJ: Rutgers University Press, 1995), 118-20.
129 "I have never seen Freireich in a moderate mood": Emil Frei III, "Confrontation, Passion, and Personalization," Clinical Cancer Research 3 (1999): 2558.
129 Gordon Zubrod, the new director: Emil Frei III, "Gordon Zubrod, MD," Journal of Clinical Oncology 17 (1999): 1331. Also see Taylor, Pioneers in Pediatric Oncology, 117.
130 Freireich came just a few weeks later: Grant Taylor, Pioneers in Pediatric Oncology (Houston: University of Texas M. D. Anderson Cancer Center, 1990), 117.
130 "Frei's job," one researcher recalled: Edward Shorter, The Health Century (New York: Doubleday, 1987), 192.
130 To avert conflicts: Andrew M. Kelahan, Robert Catalano, and Donna Marinucci, "The History, Structure, and Achievements of the Cancer Cooperative Groups," (May/June 2000): 28-33.
131 "For the first time": Robert Mayer, interview with author, July 2008. Also see Frei, "Gordon Zubrod," 1331; and Taylor, Pioneers in Pediatric Oncology, 117.
131 Hill and randomized trials: Austin Bradford Hill, Principles of Medical Statistics (Oxford: Oxford University Press, 1966); A. Bradford Hill, "The Clinical Trial," British Medical Bulletin 7, no. 4 (1951): 278-82.
132 "The analogy of drug resistance": Emil Freireich, interview with author, September 2009.
132 The first protocol was launched: Emil Frei III et al., "A Comparative Study of Two Regimens of Combination Chemotherapy in Acute Leukemia," Blood 13, no. 12 (1958): 1126-48; Richard Schilsky et al., "A Concise History of the Cancer and Leukemia Group B," Clinical Cancer Research 12, no. 11, pt. 2 (2006): 3553s-55s.
133 "This work is one of the first comparative studies": Frei et al., "Comparative Study of Two Regimens."
134 "The resistance would be fierce": Emil Freireich, personal interview.
134 a "butcher shop": Vincent T DeVita, Jr. and Edward Chu, "A History of Cancer Chemotherapy," Cancer Research 68, no. 21 (2008): 8643.
An Early Victory
135 But I do subscribe to the view: Brian Vastag, "Samuel Broder, MD, Reflects on the 30th Anniversary of the National Cancer Act," Journal of the American Medical Association 286 (2001): 2929-31.
135 Min Chiu Li: Emil J. Freireich, "Min Chiu Li: A Perspective in Cancer Therapy," Clinical Cancer Research 8 (2002): 2764-65.
136 Li and Ethel Longoria: Mickey Goulian, interview with author, September 2007.
136 "She was bleeding so rapidly": Ibid.
137 Li and Hertz rushed to publish: M. C. Li, R. Hertz, and D. M. Bergenstal, "Therapy of Choriocarcinoma and Related Trophoblastic Tumors with Folic Acid and Purine Antagonists," New England Journal of Medicine 259, no. 2 (1958): 66-74.
137 Li's use of hcg level in chemotherapy: John Laszlo, The Cure of Childhood Leukemia: Into the Age of Miracles (New Brunswick, NJ: Rutgers University Press, 1995), 145-47.
137 In mid-July, the board summoned: Ibid.
137 "Li was accused of experimenting on people": Emil Freireich, interview with author, September 2009.
138 When Freireich heard about Li's dismissal: Laszlo, Cure of Childhood Leukemia, 145.
Mice and Men
139 A model is a lie that helps: Margie Patlak, "Targeting Leukemia: From Bench to Bedside," FASEB Journal 16 (2002): 273E.
139 "Clinical research is a matter of urgency": John Laszlo, The Cure of Childhood Leukemia: Into the Age of Miracles (New Brunswick, NJ: Rutgers University Press, 1995.
139 To test three drugs, the group insisted: Ibid., 142.
139 "The wards were filling up with these terribly sick children": Emil Freireich, interview, September 2009.
139 Vincristine had been discovered in 1958: Norman R. Farnsworth, "Screening Plants for New Medicines," in Biodiversity, ed. E. O. Wilson (Washington, DC: National Academy Press, 1988), 94; Normal R. Farnsworth, "Rational Approaches Applicable to the Search for and Discovery of New Drugs From Plants," in Memorias del 1er Symposium Latinoamericano y del Caribe de Farmacos Naturales, La Habana, Cuba, 21 al 28 de Junio, 1980, 27-59 (Montevideo, Uruguay: UNESCO Regional Office Academia de Ciencias de Cuba y Comision Nacional de Cuba ante la UNESCO).
140 "Frei and Freireich were simply taking drugs": David Nathan, The Cancer Treatment Revolution (Hoboken, NJ: Wiley, 2007), 59.
140 A scientist from Alabama, Howard Skipper: Laszlo, Cure of Childhood Leukemia, 199-209.
141 Skipper emerged with two pivotal findings: See, for example, Howard E. Skipper, "Cellular Kinetics Associated with 'Curability' of Experimental Leukemias," in William Dameshek and Ray M. Dutcher, eds., Perspectives in Leukemia (New York: Grune & Stratton, 1968), 187-94.
141 "Maximal, intermittent, intensive, up-front": Emil Frei, "Curative Cancer Chemotherapy," Cancer Research 45 (1985): 6523-37.
VAMP
143 If we didn't kill the tumor: William C. Moloney and Sharon Johnson, Pioneering Hematology: The Research and Treatment of Malignant Blood Disorders--Reflections on a Life's Work (Boston: Francis A. Countway Library of Medicine, 1997).
143 "I wanted to treat them with full doses of vincristine": John Laszlo, The Cure of Childhood Leukemia: Into the Age of Miracles (New Brunswick, NJ: Rutgers University Press, 1995), 141.
143 "poison of the month": Edward Shorter, The Health Century (New York: Doubleday, 1987), 189.
144 Farber, for one, favored giving one drug at a time: See David Nathan, The Cancer Treatment Revolution (Hoboken, NJ: Wiley, 2007), 63.
144 "Oh, boy," Freireich recalled: Emil Freireich, interview with author, September 2009.
145 "You can imagine the tension": Laszlo, Cure of Childhood Leukemia, 143.
145 First VAMP trial: E. J. Freireich, M. Karon, and E. Frei III, "Quadruple Combination Therapy (VAMP) for Acute Lymphocytic Leukemia of Childhood," Proceedings of the American Association for Cancer Research 5 (1963): 20; E. Frei III, "Potential for Eliminating Leukemic Cells in Childhood Acute Leukemia," Proceedings of the American Association for Cancer Research 5 (1963): 20.
145 "I did little things": Laszlo, Cure of Childhood Leukemia, 143-44.
145 "like a drop from a cliff with a thread tied": Mickey Goulian, interview with author, September 2007.
145 The patient "is amazingly recovered": Letter from a Boston physician to patient K.L. (name withheld). K.L., interview with author, September 2009.
146 "The mood among pediatric oncologists changed": Jonathan B. Tucker, Ellie: A Child's Fight against Leukemia (New York: Holt, Rinehart, and Winston, 1982).
146 In September 1963, not long after Frei and Freireich: Freireich, interview with author.
146 "Some of us didn't make much of it at first": Goulian, interview with author.
146 By October, there were more children back at the clinic: Freireich, interview with author.
147 "I know the patients, I know their brothers and sisters": "Kids with Cancer," Newsweek, August 15, 1977.
147 morale at the institute to the breaking point: Freireich, interview with author.
148 A few, a small handful: Emil Frei, "Curative Cancer Chemotherapy," Cancer Research 45 (1985): 6523-37.
150 he triumphantly brought photographs of a few: Harold P. Rusch, "The Beginnings of Cancer Research Centers in the United St
ates," 74 (1985): 391-403.
150 further proof was "anticlimactic and unnecessary": Ibid.
150 "We are attempting": Sidney Farber, letter to Etta Rosensohn, Mary Lasker Papers, Columbia University.
An Anatomist's Tumor
151 It took plain old courage to be a chemotherapist: Vincent T. DeVita Jr. and Edward Chu, "A History of Cancer Chemotherapy," Cancer Research 68, no. 21 (2008): 8643-53.
156 Hodgkin was born in 1798 to a Quaker family: Louis Rosenfeld, Thomas Hodgkin: Morbid Anatomist & Social Activist (Lanham, MD: Madison Books, 1993), 1. Also see Amalie M. Kass and Edward H. Kass, Perfecting the World: The Life and Times of Dr. Thomas Hodgkin, 1798-1866 (Boston: Harcourt Brace Jovanovich, 1988).
157 a series of cadavers, mostly of young men: T. Hodgkin, "On Some Morbid Appearances of the Absorbent Glands and Spleen," Medico-Chirurgical Transactions 17 (1832): 68-114. The paper was read to the society by Robert Lee because Hodgkin was not a member of the society himself.
157 "A pathological paper may perhaps be thought": Hodgkin, "On Some Morbid Appearances," 96.
157 In 1837, after a rather vicious political spat: Marvin J. Stone, "Thomas Hodgkin: Medical Immortal and Uncompromising Idealist," Baylor University Medical Center Proceedings 18 (2005): 368-75.
157 In 1898, some thirty years after Hodgkin's death: Carl Sternberg, "Uber eine eigenartige unter dem Bilde der Pseudoleu Kamie Verlaufende Tuberkuloses des Lymphatischen Apparates," Ztschr Heitt 19 (1898): 21-91.
158 more "capricious," as one oncologist put it: A. Aisenberg, "Prophylactic Radiotherapy in Hodgkin's Disease," New England Journal of Medicine 278, no. 13 (1968): 740; A. Aisenberg, "Management of Hodgkin's Disease," New England Journal of Medicine 278, no. 13 (1968): 739; A. C. Aisenberg, "Primary Management of Hodgkin's Disease," New England Journal of Medicine 278, no. 2 (1968): 92-95.
158 the plan to build a linear accelerator: Z. Fuks and M. Feldman, "Henry S. Kaplan, 1918-1984: A Physician, a Scientist, a Friend," Cancer Surveys 4, no. 2 (1985): 294-311.
159 In 1953, he persuaded a team: Malcolm A. Bagshaw, Henry E. Jones, Robert F. Kallman, and Joseph P. Kriss, "Memorial Resolution: Henry S. Kaplan (1918-1984)," Stanford University Faculty Memorials, Stanford Historical Society, http://histsoc.stanford.edu/pdfmem/KaplanH.pdf (accessed November 22, 2009).
159 The accelerator was installed: Ibid.
159 "Henry Kaplan was Hodgkin's disease": George Canellos, interview with author, March 2008.
159 Rene Gilbert had shown: R. Gilbert, "Radiology in Hodgkin's Disease [malignant granulomatosis]. Anatomic and Clinical Foundations," American Journal of Roentgenology and Radium Therapy 41 (1939): 198-241; D. H. Cowan, "Vera Peters and the Curability of Hodgkin's Disease," Current Oncology 15, no. 5 (2008): 206-10.
160 Peters observed that broad-field radiation could: M. V. Peters and K. C. Middlemiss, "A Study of Hodgkin's Disease Treated by Irradiation," American Journal of Roentgenology and Radium Therapy 79 (1958): 114-21.
160 The trials that Kaplan designed: H. S. Kaplan, "The Radical Radiotherapy of Regionally Localized Hodgkin's Disease," Radiology 78 (1962): 553-61; Richard T. Hoppe, Peter T. Mauch, James O. Armitage, Volker Diehl, and Lawrence M. Weiss, Hodgkin Lymphoma (Philadelphia: Lippincott Williams & Wilkins, 2007), 178.
160 "meticulous radiotherapy": Aisenberg, "Primary Management of Hodgkin's Disease," 95.
160 But Kaplan knew that a diminished relapse rate was not a cure: H. S. Kaplan, "Radical Radiation for Hodgkin's Disease," New England Journal of Medicine 278, no. 25 (1968): 1404; H. S. Kaplan, "Clinical Evaluation and Radiotherapeutic Management of Hodgkin's Disease and the Malignant Lymphomas," New England Journal of Medicine 278, no. 16 (1968): 892-99.
161 "Fundamental to all attempts at curative treatment": Aisenberg, "Primary Management of Hodgkin's Disease," 93.
An Army on the March
162 Now we are an army on the march: "Looking Back: Sidney Farber and the First Remission of Acute Pediatric Leukemia," Children's Hospital Boston, http://www.childrenshospital.org/gallery/index.cfm?G=49&page=1 (accessed November 22, 2009).
162 The next step--the complete cure: Kenneth Endicott, quoted in the Mary Lasker Papers, "Cancer Wars," National Library of Medicine.
162 The role of aggressive multiple drug therapy: R. C. Stein et al., "Prognosis of Childhood Leukemia," Pediatrics 43, no. 6 (1969): 1056-58.
162 George Canellos, then a senior fellow at the NCI: George Canellos, interview with author, March 2008.
163 "A new breed of cancer investigators in the 1960s": V. T. DeVita Jr., British Journal of Haematology 122, no. 5 (2003): 718-27.
164 "maniacs doing cancer research": Ronald Piana, "ONI Sits Down with Dr. Vincent DeVita," Oncology News International 17, no. 2 (February 1, 2008), http://www.consultantlive.com/display/article/10165/1146581?pageNumber=2&verify=0 (accessed November 22, 2009).
164 As expected: See Vincent T. DeVita Jr. and Edward Chu, "A History of Cancer Chemotherapy," Cancer Research 21: 8643.
164 The MOPP trial: Vincent T. DeVita Jr. et al., "Combination Chemotherapy in the Treatment of Advanced Hodgkin's Disease," Annals of Internal Medicine 73, no. 6 (1970): 881-95.
166 A twelve-year-old boy: Bruce Chabner, interview with author, July 2009.
166 "Some of the patients with advanced disease": Henry Kaplan, Hodgkin's Disease (New York: Commonwealth Fund, 1972), 15, 458. Also see DeVita et al., "Combination Chemotherapy in the Treatment."
167 "no track record, uncertain finances, an unfinished building": Joseph V. Simone, "A History of St. Jude Children's Research Hospital," British Journal of Haematology 120 (2003): 549-55.
168 "an all-out combat": R. J. Aur and D. Pinkel, "Total Therapy of Acute Lymphocytic Leukemia," Progress in Clinical Cancer 5 (1973): 155-70.
168 "in maximum tolerated doses": Joseph Simone et al., "'Total Therapy' Studies of Acute Lymphocytic Leukemia in Children: Current Results and Prospects for Cure," Cancer 30, no. 6 (1972): 1488-94.
168 it was impossible to even dose it and monitor it correctly: Aur and Pinkel, "Total Therapy of Acute Lymphocytic Leukemia."
168 senior researchers, knowing its risks: "This Week's Citations Classic: R. J. A. Aur et al., "Central Nervous System Therapy and Combination Chemotherapy of Childhood Lymphocytic Leukemia," Citation Classics 28 (July 14, 1986).
169 "From the time of his diagnosis": Jocelyn Demers, Suffer the Little Children: The Battle against Childhood Cancer (Fountain Valley, CA: Eden Press, 1986), 17.
170 In July 1968, the St. Jude's team published: Donald Pinkel et al., "Nine Years' Experience with 'Total Therapy' of Childhood Acute Lymphocytic Leukemia," Pediatrics 50, no. 2 (1972): 246-51.
170 The longest remission was now in its sixth year: S. L. George et al., "A Reappraisal of the Results of Stopping Therapy in Childhood Leukemia," New England Journal of Medicine 300, no. 6 (1979):269-73.
170 In 1979, Pinkel's team revisited: Donald Pinkel, "Treatment of Acute Lymphocytic Leukemia" Cancer 23 (1979): 25-33.
170 "ALL in children cannot be considered an incurable disease": Pinkel et al, "Nine Years' Experience with 'Total Therapy.'"
The Cart and the Horse
171 I am not opposed to optimism: P. T. Cole, "Cohorts and Conclusions," New England Journal of Medicine 278, no. 20 (1968): 1126-27.
171 The iron is hot and this is the time: Letter from Sidney Farber to Mary Lasker, September 4, 1965.
171 In the late fifties, as DeVita recalled: Vincent T. DeVita Jr. and Edward Chu, "A History of Cancer Chemotherapy," Cancer Research 68, no. 21 (2008): 8643-53.
171 "A revolution [has been]": Vincent T. DeVita Jr., "A Selective History of the Therapy of Hodgkin's Disease," British Journal of Hemotology 122 (2003): 718-27.
171 The next step--the complete cure: Kenneth Endicott, quoted in "Cancer Wars," Mary Lasker Papers, Profiles in Science, National Libraries of Medicine. Also see V. T. DeVita Jr., "A Perspective on the War on Cancer," Cancer Journal 8, no. 5 (2002): 352-56.
172 "The chemi
cal arsenal," one writer noted: Ellen Leopold, A Darker Ribbon: Breast Cancer, Women, and Their Doctors in the Twentieth Century (Boston: Beacon Press, 1999), 269-70.
173 "one cause, one mechanism and one cure": "Fanfare Fades in the Fight against Cancer," U.S. News and World Report, June 19, 1978.
173 Peyton Rous: Heather L. Van Epps, "Peyton Rous: Father of the Tumor Virus," Journal of Experimental Medicine 201, no. 3 (2005): 320; Peter K. Vogt, "Peyton Rous: Homage and Appraisal," Journal of the Federation of American Societies for Experimental Biology 10 (1996): 1559-62.
173 Peyton Rous's work on sarcomas in chickens: Peyton Rous, "A Transmissible Avian Neoplasm (Sarcoma of the Common Fowl)," Journal of Experimental Medicine 12, no. 5 (1910): 696-705; Peyton Rous, "A Sarcoma of the Fowl Transmissible by an Agent Separable from the Tumor Cells," Journal of Experimental Medicine 13, no. 4 (1911): 397-411.
174 "I have propagated a spindle-cell sarcoma": Rous, "A Transmissible Avian Neoplasm."
174 Richard Schope reported a papillomavirus: Richard E. Shope, "A Change in Rabbit Fibroma Virus Suggesting Mutation: II. Behavior of the Varient Virus in Cottontail Rabbits," Journal of Experimental Medicine 63, no. 2 (1936): 173-78; Richard E. Shope, "A Change in Rabbit Fibroma Virus Suggesting Mutation: III. Interpretation of Findings," Journal of Experimental Medicine 63, no. 2 (1936): 179-84.
174 Denis Burkitt, discovered an aggressive form of lymphoma: Denis Burkitt, "A Sarcoma Involving the Jaws in African Children," British Journal of Surgery 46, no. 197 (1958): 218-23.
175 "Cancer may be infectious": "New Evidence That Cancer May Be Infectious," Life, June 22, 1962. Also see "Virus Link Found," Los Angeles Times, November 30, 1964.
175 "Is there something I can do to kill the cancer germ?": Letter from Mary Kirkpatrick to Peyton Rous, June 23, 1962, Peyton Rous papers, the American Philosophical Society, quoted in James T. Patterson, The Dread Disease: Cancer and Modern American Culture (Cambridge, MA: Harvard University Press, 1987), 237.
175 the NCI inaugurated a Special Virus Cancer Program: Nicholas Wade, "Special Virus Cancer Program: Travails of a Biological Moonshot," Science 174, no. 4016(1971): 1306-11.
Siddhartha Mukherjee - The Emperor of All Maladies: A Biography of Cancer Page 60