Manhattan transfer: Lethal radiation, bone marrow transplantation, and the birth of stem cell biology, ca. 1942-1961

Historical Studies in the Natural Sciences

Volumn 39, Issue 2, 2009, Pages 171-218

  Kraft, Alison ^a  

^a UNIVERSITY OF NOTTINGHAM   (United Kingdom)

Author keywords

Bone marrow transplantation; E. Donnall Thomas; Egon Lorenz; Harwell; John F. Loutit; Leon Jacobson; Leukemia; Manhattan Project; Nuclear reactor; Radiobiology; Stem cell; Whole body irradiation

Indexed keywords

ARTICLE; BONE MARROW TRANSPLANTATION; ECONOMICS; EDUCATION; ETHNOLOGY; HISTORY; LABORATORY PERSONNEL; LEGAL ASPECT; LEUKEMIA; MEDICAL RESEARCH; NUCLEAR MEDICINE; NUCLEAR REACTOR; PERSONNEL; PHYSIOLOGY; PSYCHOLOGICAL ASPECT; PUBLIC HEALTH; PUBLIC HEALTH SERVICE; RADIOBIOLOGY; STEM CELL; WHOLE BODY RADIATION;

BIOMEDICAL RESEARCH; BONE MARROW TRANSPLANTATION; HISTORY, 20TH CENTURY; LABORATORY PERSONNEL; LEUKEMIA; NUCLEAR MEDICINE; NUCLEAR REACTORS; PUBLIC HEALTH; PUBLIC HEALTH PRACTICE; RADIOBIOLOGY; RESEARCH PERSONNEL; STEM CELLS; WHOLE-BODY IRRADIATION;

EID: 77950353082     PISSN: 19391811     EISSN: 1939182X     Source Type: Journal    
DOI: 10.1525/hsns.2009.39.2.171     Document Type: Review

References (202)

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51. Eugene Goldwasser, Jake, Leon O. Jacobson, M.D.: The Life and Work of a Distinguished Medical Scientist (Sagamore Beach, MA: Science History Publications, 2006), 23
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55. Stone, "Plutonium Project" (ref. 23), 269 and 364
56. The tolerance dose was reduced by 50 percent to 0.1 r/day when it was also replaced by the maximum permissible dose. Henry S. Kaplan, "Obituary for Egon Lorenz," JNCI 15, no. 4 (1955): iii-v
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58. For further analysis of the ways in which the postwar upsurge in state funds for research shaped the life sciences in the U.S., see Toby A. Appel, Shaping Biology: The National Science Foundation and American Biological Research 1945-1975 (Baltimore, MD: Johns Hopkins University Press, 2000)
59. Harvey M. Sapolsky, Science and the Navy: The History of the Office of Naval Research (Princeton: Princeton University Press, 1990), 4
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61. On the postwar development of the U.S. National Laboratory system see Peter Westwick, The National Labs: Science in an American System, 1947-1974 (Cambridge, MA: Harvard University Press, 2003)
62. Robert W. Seidel, "A Home for Big Science: The Atomic Energy Commission's Laboratory System," HSPS 16, no. 1 (1986): 135-75
63. Donald C. Swain, "The Rise of a Research Empire: NIH 1930 to 1950," Science 138, no. 3456 (1962): 1233-37
64. Stephen P. Strickland, "Integration of Medical Research and Health Policies," Science 173, no. 4002 (1971), 1093-103
65. Buhm Soon Park, "The Development of the Intramural Research Program at the National Institutes of Health after World War II," Perspectives in Biology and Medicine 46, no. 3 (2003): 383-402. For an overview of the radiobiological research activities of the USPHS and NIH in the late 1940s, see RCUT, Alexander Hollaender Collection/ MS 1261, Box 4, Folder USPHS. In the U.S., cancer research also continued to be strongly supported by charities such as the American Cancer Society
66. Creager, "Nuclear Energy" (ref. 9)
67. On the postwar development of the AEC, see Richard G. Hewlett and Francis Duncan, Atomic Shield 1947/1952: A History of the United States Atomic Energy Commission, Volume II (University Park: Pennsylvania State University Press, 1969)
68. Richard G. Hewlett and Francis Duncan, Nuclear Navy 1946-1962 (Chicago: University of Chicago Press, 1974)
69. John E. Pfeiffer, "The Office of Naval Research," Scientific American 180, no. 2 (1949): 11-15
70. Sapolsky, Science and the Navy (ref. 47). The ONR filled a gap between the disbanding of the OSRD in 1945 and the establishment of the National Science Foundation in 1950
71. de Chadarevian, "Mice and the Reactor" (ref. 7)
72. Mary F. Lyon and P. L. Mollison, obituary for John Freeman Loutit, Biographical Memoirs of Fellows of the Royal Society 40 (1994): 238-52
73. "The Radiobiological Research Unit, Harwell," Nature 193, no. 4814 (1962): 428-29
74. Comments of William L. Lawrence of the U.S. War Department in 1946, quoted in Robert S. Stone, "Health Protection Activities of the Plutonium Project," Proceedings of the American Philosophical Society 90, no. 1 (1946): 11-19
75. Clifford Ladd Prosser, "The Clinical Sequence of Physiological Effects of Ionizing Radiation in Animals," Radiology 49 (1947): 299-313, on 299
76. Newspaper clipping, LOJC, Box 18, Folder Clippings 1935-1951
77. Eugene P. Cronkite, "Ionizing Radiation Injury," JAMA 139, no. 6 (1949): 366-69
78. "The Diagnosis, Prognosis, and Treatment of Radiation Injuries Produced by Atomic Bombs," Radiology 56 (1951): 661-69
79. John F. Loutit and W. D'A Maycock, "The Treatment of Radiation Casualties," The Practitioner 165, no. 990 (1950): 607-14
80. Kutcher, "Cancer Therapy" (ref. 10), 111
81. On the growing awareness of the dangers of radioactive fallout, see David Bradley, No Place to Hide (Boston: Little, Brown, 1948)
82. Paul Boyer, Fallout: A Historian Reflects on America's Half-Century Encounter with Nuclear Weapons (Columbus: Ohio State University Press, 1998)
83. Barton C. Hacker, Elements of Controversy: The Atomic Energy Commission and Radiation Safety in Nuclear Weapons Testing, 1947-1974 (Berkeley: University of California Press, 1994)
84. Allan M. Winkler, Life under a Cloud: American Anxiety about the Atom (Oxford: Oxford University Press, 1993)
85. Spencer Weart, Nuclear Fear: A History of Images (Cambridge, MA: Harvard University Press, 1988)
86. Charles C. Congdon and Alexander Hollaender, "Experimental Applications of Bone Marrow Transplantation," Archives of Pathology 69 (1960): 605-12, on 605-06
87. Lindee, Suffering (ref. 4), 258; LOJC, Box 9, Folder 258
88. "Prophylactic Radiation Protection," New Scientist 1, no. 19 (1957): 8
89. "A Possible Cure for Radiation Sickness," New Scientist 3, no. 61 (1958): 8
90. John Hersey, "Hiroshima," The New Yorker, 31 Aug 1946
91. Nevil Shute, On the Beach (London: Heinemann, 1957)
92. Walter Miller, Jr., A Canticle for Leibowitz (Philadelphia: Lippincott, Williams, and Wilkins, 1960)
93. Exemplified in civil defense initiatives and in plans for the mobilization of medical help. John Z. Bowers, "Acute Radiation Syndrome: A Problem for Practitioners," JAMA 145, no. 2 (1951): 63-65
94. James P. Cooney, "The Physician's Problem in Atomic Warfare," JAMA 145, no. 9 1951): 634-37
95. Shields Warren, "Atomic Energy in War and Peace: Medical Aspects," JAMA 145, no. 2 (1951): 61-62
96. Paul Boyer, "Physicians Confront the Apocalypse," JAMA 254, no. 5 (1985): 633-43
97. For insights into some aspects of this issue in the U.K., see Jeffrey A. Hughes, "The Strath Report: Britain Confronts the H-Bomb, 1954-1955," History and Technology 19, no. 3 (2003): 257-75
98. Patt, "Protective Mechanisms" (ref. 19), 35-76
99. David Doherty and W. T. Burnett, "The Protective Effect of S, B-aminoethylisothiouronium Br-H Brand Related Compounds against X-Radiation Death in Mice," Proceedings of the Society of Experimental Biology and Medicine 89 (1955): 312-14
100. This rested on the concept of differential sensitivity of normal and malignant tissue to radiation: if this differential could be chemically modified, by the addition of "radioprotective" compounds, it was reasoned that perhaps this offered the means to better target therapy to diseased tissue while also reducing damage to healthy tissue. In practice this proved of little use clinically. See John F. Loutit, "Protection against Radiation with Chemical Agents," typed manuscript, ca. 1954, MRC, Harwell
101. Alexander Hollaender, Radiation Protection and Recovery (New York: Pergamon Press, 1960)
102. Robert M. Straube and Harvey M. Patt, "Chemical Protection against Ionizing Radiation," Annual Review of Pharmacology 3 (1963): 293-306
103. Leon O. Jacobson, Edna K. Marks, Edith O. Gaston, M. Robson, and Raymond Zirkle, "The Role of the Spleen in Radiation Injury," Proceedings of the Society for Experimental Biology and Medicine 70, no. 2 (1949): 740-42
104. This work was disseminated first via Symposia at Annual Meetings of the U.S. Radiological Society in 1946 and subsequently published in Radiology in 1947 (ref. 42). After the war Jacobson became a leading figure in the Medical School at the University of Chicago, having been appointed as Director of the Argonne Cancer Hospital in 1951
105. Feffer, "Atoms" (ref. 46), 255-62
106. Leon O. Jacobson, "Serendipity Works," Experimental Hematology 22, no. 1 (1972): 3-5
107. Eugene Cronkite, "Introduction" (to the Nucleonics Panel on Harmful Effects of Irradiation on Hemopoiesis and its Accelerated Restoration), in Proceedings of the Sixth International Congress of the International Society of Hematology, 27 Aug-1 Sep 1956 (New York: Grune and Stratton, 1958), 370
108. Leon O. Jacobson, "Modification of Radiation Injury in Experimental Animals," American Journal of Roentgenology: Radium Therapy and Nuclear Medicine 72, no. 4 (1954): 543-55
109. Goldwasser, Jake (ref. 33), 35
110. Chicago Sun Times, 24 Dec 1952
111. Leon Jacobson, Robert S. Stone, and J. Garrott Allen, "The Physician's Role in War," JAMA 139 (1949): 138-40
112. "The Problem of Radiation Injury," LOJC, Box 6, Folder 1951
113. Leon O. Jacobson, "Further Studies on Recovery from Radiation Injury," Journal of Laboratory and Clinical Medicine 37, no. 5 (1951): 683-97
114. Leon O. Jacobson, "Evidence for a Humoral Factor (or Factors) Concerned in Recovery from Radiation Injury: A Review," Cancer Research 12, no. 5 (1952): 315-25
115. For insights into the turmoil within hematology in this period, see Keith Wailoo, Drawing Blood: Technology and Disease Identity in Twentieth Century America (Baltimore, MD: Johns Hopkins University Press, 1999), esp. chap. 6
116. William Dameshek, Editorial, Blood 2, no. 1 (1947): 101
117. William Dameshek, Foreword, Blood 6, no. 1 (1951): 1-2
118. Jacobson, "Further Studies" (ref. 88). Significantly, Jacobson's paper also reported that the spleen-based "recovery effects" were also observed following exposure to nitrogen mustard, an important finding from the point of view of new chemotherapeutic approaches to and treatments for cancer emerging in this period. From his days in the Toxicology Laboratory during the Manhattan Project, Jacobson was actively involved in research into the use of the nitrogen mustards as a treatment for leukemia
119. Jacobson et al., "Nitrogen Mustard Therapy: Studies on the Effect of Methyl-Bis (Beta Chloroethyl) on Neoplastic and Allied Disorders of the Hematopoietic System," JAMA 132 (1946): 263-71
120. William Dameshek, "ACTH and its Hematologic Impact," Editorial, Blood 5, no. 8 (1950): 779-80
121. J. Fabricius-Møller, Experimental Studies of the Hemorrhagic Diathesis from X-ray Sickness (Copenhagen: Levin and Munksgaard Forlag, 1922)
122. Edwin E. Osgood, M. C. Riddle, and T. J. Mathews, "Aplastic Anemia Treated with Daily Infusions and Intravenous Marrow," Annals of Internal Medicine 13 (1939): 357-67
123. Peter E. Rekers, M. P. Coulter, and S. L. Warren, "Effect of Transplantation of Bone Marrow into Irradiated Animals," Archives of Surgery 60 (1950): 635-67
124. Kaplan, "Lorenz Obituary" (ref. 44)
125. Egon Lorenz, Delta Uphoff, T. R. Reid, and Emma Shelton, "Modification of Irradiation Injury in Mice and Guinea Pigs by Bone Marrow Injection," JNCI 12 (1951): 197-201
126. Charles C. Congdon, "Recovery from Radiation Injury with Special Consideration of the Use of Bone Marrow Transplantation," Progress in Hematology 2 (1959): 21-46. Lorenz's thinking was informed by the extramedullary role of the spleen in hematopoiesis in the mouse, his idea being to explore whether this role was connected to its apparent protective effect when the bone marrow had sustained radiation damage
127. Charles C. Congdon, interview by author, 3 Oct 2008, Knoxville, TN
128. Charles C. Congdon, Delta Uphoff, and Egon Lorenz, "Modification of Acute Irradiation Injury in Mice and Guinea Pigs by Injection of Bone Marrow: A Histopathologic Study," JNCI 13 (1952): 73-107
129. Egon Lorenz and Charles C. Congdon, "Modification of Lethal Irradiation Injury in Mice by Injection of Homologous and Heterologous Bone Marrow," JNCI 14 (1954): 955-65
130. Lorenz et al., "Modification of Irradiation Injury" (ref. 97), 200
131. Terry Shinn and Bernward Joerges, "The Transverse Science and Technology Culture: Dynamics and Roles of Research-Technology," Social Science Information 41 (2002): 207-51
132. Alison Kraft, "BMT as an Experimental System," manuscript
133. Jacobson, "Modification" (ref. 81)
134. John F. Loutit, "Lectures on the Scientific Basis of Medicine" (1955-56), Loutit Collection, MRC Library, Harwell
135. David W. H. Barnes and John F. Loutit, "Spleen Protection: The Cellular Hypothesis" in Radiobiology Symposium, ed. Zénon M. Bacq and Peter Alexander (London: Butterworths, 1954), 134-35
136. David W. H. Barnes and John F. Loutit, "The Radiation Recovery Factor: Preservation by the Polge Smith-Parkes Technique," JNCI 15 (1955): 901-05. Here Barnes and Loutit reported results using this method of tissue preservation, which in their views was consistent with the "recovery factor" being a cellular rather than hormonal entity. That the factor was more effective in bringing about recovery when applied intravenously than when given intraperitoneally was also interpreted by the Harwell group as indicative of a cellular rather than a hormonal agent
137. David W. H. Barnes and John F. Loutit, "What Is the Recovery Factor in Spleen?," Nucleonics 12 (1954): 68-71. This letter responded to an article in Nucleonics the preceding December, which reported that extracts of spleen were effective in aiding recovery from damage by radiation
138. Alma Howard and Michael Ebert, "Current Research in Radiobiology," Nucleonics 11 (1953): 18-23
139. John F. Loutit, "Protection against Ionizing Radiation: The 'Recovery Factor' in Spleen and Bone Marrow," Journal of Nuclear Energy 1 (1954): 87-91, on 90
140. Jan A. Witkowski, "Dr. Carrel's Immortal Cells," Medical History 24 (1980): 129-42
141. Duncan Wilson, "The Early History of Tissue Culture in Britain: The Interwar Years," Social History of Medicine 18, no. 2 (2005): 225-43
142. Charles C. Congdon and Egon Lorenz, "Humoral Factor in Irradiation Protection: Modification of Lethal Irradiation Injury in Mice by Injection of Rat Bone Marrow," American Journal of Physiology 176, no. 2 (1954): 297-300
143. Charles E. Ford, John L. Hamerton, David W. H. Barnes, and John F. Loutit, "Cytological Identification of Radiation Chimeras," Nature 177 (1956): 452-54, on 454
144. Rupert E. Billingham, Leslie Brent, and Peter B. Medawar, "'Actively Acquired Tolerance' of Foreign Cells," Nature 172 (1953): 603-06, in which they reported the phenomenon in cows of acquired tolerance in utero
145. Frank Macfarlane Burnet, Cellular Immunology: Self and Not-Self (Melbourne: Melbourne University Press, 1969)
146. Joan M. Main and Richmond T. Prehn, "Successful Skin Homografts after the Administration of High Dosage X-Radiation and Homologous Bone Marrow," JNCI 15 (1955): 1023-29, on 1027
147. Charles E. Ford, "Use of Distinctive Chromosomes to Identify Cells Transplanted by Injection," Transplantation Bulletin 3 (1956): 82
148. Dirk van Bekkum and Jan de Vries, Radiation Chimeras (London: Logos Press,1967), ix
149. Ford et al., "Cytological" (ref. 111), 452
150. The term chimera denotes "an animal the constituent cells of which are of more than one genotype or antigenic lineage." Classically the chimera was part goat, lion, and serpent. For an authoritative review of radiation chimeras and their experimental value, see van Bekkum and de Vries, Chimeras (ref. 115)
151. Daniel L. Lindsley, T. T. Odell, and F. G. Tausche, "Implantation of Functional Erythropoietic Elements Following Total Body Irradiation," Proceedings of the Society for Experimental Biology and Medicine 90, no. 2 (1955): 512-15. In their 1956 paper, Ford et al. acknowledged this paper as an addendum, having been published between submission and publication of their own paper
152. Peter C. Nowell, Leonard J. Cole, John G. Habermeyer, and Patricia L. Roan, "Growth and Continued Function of Rat Marrow Cells in X-Radiated Mice," Cancer Research 16 (1956): 258-61
153. O. Vos, J. A. G. Davids, W. W. H. Weyzen, and Dirk W. van Bekkum, "Evidence for the Cellular Hypothesis in Radiation Protection by Bone Marrow Cells," Acta physiologica et pharmacologica Neerlandica 4, no. 4 (1956): 482-86
154. Nicolas A. Mitchison, "The Colonization of Irradiated Tissue by Transplanted Spleen Cells," British Journal of Experimental Pathology 37 (1956): 239-47
155. Charles C. Congdon, "Experimental Treatment of Total-Body Irradiation Injury: A Brief Review," Blood 12, no. 8 (1957): 746-54, on 751
156. John F. Loutit, "Transplantation of Haematopoietic Tissues," British Medical Bulletin 21, no. 2 (1965): 118-22, on 119
157. John F. Loutit, "British Medical Bulletin Ibid., 119
158. Congdon, "Experimental Treatment" (ref. 122)
159. Leon O. Jacobson, "Some Problems in Hematology," LOJC, typed manuscript ca. 1971, Box 6, Folder Image/Roche Medical
160. Merrill Goozner, The $800 Million Pill: The Truth behind the Cost of New Drugs (Berkeley: University of California Press, 2004). This hormone came subsequently to provide the basis for the blockbuster drug EPO, used in the treatment of anemia, the leukemias, and renal diseases
161. Jacobson, "Serendipity" (ref. 79)
162. Charles C. Congdon, personal communication, Jun 2008
163. Westwick, National Labs (ref. 48). Philanthropy too was an important source of funding in the early clinical development of BMT, which was supported by the John A. Hartford Foundation
164. David W. H. Barnes, Michael J. Corp, John F. Loutit, and Frank E. Neal, "Treatment of Murine Leukaemia with X-rays and Homologous Bone Marrow," British Medical Journal 2, no. 4993 (1956): 626-27
165. Barnes et al., "Treatment of Murine Leukaemia" (ref. 134), 627
166. Congdon and Hollaender, "Experimental Applications" (ref. 66), 608
167. Patterson, Dread Disease (ref. 2)
168. On evolving approaches within cancer therapy, see John V. Pickstone, "Contested Cumulations: Configurations of Cancer Treatments through the Twentieth Century," Bulletin of the History of Medicine 81, no. 1 (2007): 164-96
169. Ronald Bodley Scott, "The Treatment of Leukaemia," lecture given May 1958, 8, WTAL, Ronald Bodley Scott Collection/PP/RBS/C41, Folder Unpublished Papers, 1958-1960
170. The Treatment of Leukaemia," Ibid., 19-20
171. Scott, "Treatment" (ref. 142), 2
172. Lionel Whitby, "Whither Clinical Pathology? Trends and Opportunities," Journal of Clinical Pathology 4, no. 2 (1951): 129-36
173. Wailoo, Drawing Blood (ref. 89)
174. Pickstone, "Contested Cumulations" (ref. 141)
175. On the development of chemotherapy, see C. Gordon Zubrod, "Historic Milestones in Curative Chemotherapy," Seminars in Oncology 6, no. 4 (1979): 490-505
176. For a technical review of this early history of the transplantation field, see Michael Woodruff, The Transplantation of Tissues and Organs (Springfield, IL: Charles C. Thomas, 1960)
177. Joseph E. Murray, John P. Merrill, and J. Hartwell Harrison, "Renal Homotransplantation in Identical Twins," Surgical Forum 6 (1955): 432-36
178. The surge in this surgical specialism was marked by the establishment in 1953 of the Transplantation Bulletin and in 1957 of a new dedicated journal, Transplantation Medicine. On the former, see JNCI 14, no. 1 (1953): 227. Significantly, Congdon has emphasized how research findings from BMT studies fed back into the whole organ transplantation field
179. Charles C. Congdon, "Bone Marrow Transplantation," Science 171 (1971): 1116-24
180. For a technical review of BMT, see, for example, David Pegg, Bone Marrow Transplantation (London: Lloyd Luke, 1966)
181. Dirk van Bekkum and Robert Lowenberg, Bone Marrow Transplantation: Biological Mechanisms and Clinical Practice (New York: Marcel Dekker, 1985)
182. Congdon and Hollaender (ref. 66), 608
183. see also Maxwell Wintrobe, Hematology: The Blossoming of a Science: A Story of Inspiration and Effort (Philadelphia: Lea & Febiger, 1985)
184. Joseph W. Ferrebee and John P. Merrill, "Spare Parts: A Review with a Forward Look," Surgery 41, no. 3 (1957): 503-07, on 505
185. Joseph W. Ferrebee and John P. Merrill, "Surgery Ibid., 503
186. William Dameshek, Editorial, "Bone Marrow Transplantation-A Present Day Challenge," Blood 12, no. 4 (1957): 321-23
187. Leandro M. Tocantins, "Potential Clinical Applications of the Transplantation of Preserved Bone Marrow," Nucleonics Panel on the Harmful Effects of Ionizing Radiation, Proceedings of the Sixth International Congress of the International Society of Hematology, Boston, 27 Aug-1 Sep 1956 (New York: Grune and Stratton, 1958), 401-06
188. Georges Mathé, "Application of Hematopoietic Cell Grafts to the Treatment of Leukemias and Allied Diseases: A Critical Review," Blood 16, no. 2 (1960): 1073-87
189. Ferrebee and Merrill, "Spare Parts" (ref. 154)
190. Thomas et al., "Intravenous Infusion" (ref. 1). The study involved six patients, five of whom had various-and typically advanced-forms of cancer (multiple myeloma, chronic myeloid leukemia, ovarian cancer, and one with unspecified metastatic disease); from the available information, one (terminally ill) patient seems not to have had malignant disease, providing useful information on the engraftment characteristics of transplanted bone marrow in the context of a normal immune system. Three of the patients received radiation at doses of 30 r, 450 r, and 600 r; the two patients receiving chemotherapy, and the comatose patient with no malignant disease, were not given radiotherapy. Various sources of bone marrow were used: fetal and adult cadavers, ribs fr om surgery, and aspiration biopsy of the ileum
191. Proceedings of the Tenth Annual Blood Club Meeting, held 5 May 1957, Blood 13 (1958): 266-301, on 282
192. See also Laszlo Lajtha, "Consideration of the Theory of Bone Marrow Grafting as Treatment of Radiation Damage," British Journal of Radiology 33 (1960): 588-92
193. Proceedings (ref. 163), 267 and 299
194. Mortimer M. Bortin, "A Compendium of Reported Human Bone Marrow Transplants," Transplantation 9 (1970): 571-87
195. Immunology was especially important; see Leslie Brent, A History of Transplantation Immunology (San Diego: Academic Press, 1997)
196. For insight into the knowledge base on hematopoiesis, see Maxwell Wintrobe, Clinical Hematology (London: Kimpton, 1942)
197. Maxwell Wintrobe, Blood, Pure and Eloquent: A Story of Discovery, of People, and of Ideas (New York: McGraw Hill, 1980)
198. A. Pappenheim, "Prinzipien der neueren morphologischen Haematozytologie nach zytogenetischer Grundlage," Folia Haematologica 21 (1917): 91-101
199. Wintrobe, Blood, Pure and Eloquent (ref. 171), 83
200. The identity of the hematopoietic stem cell (HSC) remains controversial. Alison Kraft, Nik Brown, and Paul Martin, "Hunting the HSC," manuscript
201. James E. Till and Ernest A. McCulloch, "A Direct Measurement of the Radiation Sensitivity of Normal Mouse Bone Marrow Cells," Radiation Research 14, no. 2 (1961): 213-22
202. Hans-Jörg Rheinberger, Toward a History of Epistemic Things: Synthesizing Proteins in the Test Tube (Chicago: University of Chicago Press, 1997), 39