Industrial Medicine on the Plutonium Project (Survey and Collected Papers) First Edition, Mcgraw-Hill Book Company 1951 (Plutonium Injection Experiments)

Page 1

Survey and Collected Papers Professor of Radiology and Chairman of the Division of Radiology, University of California School of Medicine; formerly Associate Project Director for Health, Metallurgical Project, University of Chicago; Consultant, Argonne National Laboratory ATOMIC ENEXGY COV MISS I CN New York Toronto. London McGRAW-HILL BOOK COMPANY, INC.

Page 2

L. 0. Jacobson, M.D., Argonne National Laboratory and University of Chicago, Chicago pital, The Medical Center, San Francisco Edna K. Marks, Argonne National Laboratory, Chicago Norman Pearlman, M.S., Purdue University, Lafayette, Ind. Jack Schubert, Ph. D., Argonne National Laboratory, Chicago Samuel Schwartz, M.D., University of Minnesota, Minneapolis School of Medicine, San Francisco VOLUME EDITORIAL COMMITTEE

Page 3

Health Physics was developed under the supervision of Herbert M. Parker (Chicago, Clinton, Hanford), Ernest 0. Wollan (Chicago), Karl biology was directed by Kenneth S. Cole (Chicago), Joseph G. Hamilton, tional Cancer Institute). The investigations in uranium toxicolog! were carried out at Michael Reese Hospital, Chicago, under the direction of Albert Tannenbaum, M.D., as part of the program of thc Practically all the work described in the Health Volumes was don between Sept. 1, 1942, and June 30, 1945. It was subject to the usua disadvantages of wartime research and development-chiefly hast and security regulations. On the other hand, it proceeded under ver advantageous financial support. Moreover, the security regulatioi oftenhad the advantageous effect of preventing publication of researc until experiments had been verified by collateral work. Most of the writing was necessarily done rather hastily because, the early postwar period, many of the authors were returning to the regular positions in universities and elsewhere. Editing has ber done in more leisurely fashion but with a severe shortage of compc tent manpower. With unlimited editorial personnel, much of the m: terial could have been substantially shortened. Since this seem impracticable, most of the editorial effort has gone into the correcti of major e r r o r s and inconsistencies. We hope that not too many these have eluded us. Editor, Health Volume:

Page 4

Introductory Note on the Plutonium Project Record.. ......... preface to the Health Volumes in Division IV.. ............... plutonium Project Record Foreword ........................ General Introduction to Reports on Medicine, Health Physics, Medical Services of t h e Plutonium Project.. ................. Biological Bases for Maximum Permissible Exposures.. ...... Protective Measures for Personnel .........................

Page 5

Clinical Laboratory Examination of Plutonium Project By L. 0. Jacobson and Edna K. Marks Hematological Effects of Ionizing Radiations. ................ 140 By L. 0. Jacobson, Edna K. Marks, and Egon Lorenz Biochemical Studies Relating to the Effects of Radiation By Samuel Schwartz Uranium Excretion Studies.. ............................... 24 Distribution and Excretion of Plutonium.. ................... 2 Management and Treatment of Exposed Personnel.. .......... 2 Requirements of an Adequate Health Service in Relation to Atomic Research and Industrial Development ..............

Page 6

PART B. COLLECTED PAPERS Industrial Medical Program-Hanford Engineer Works.. ..... 289 Blood Changes in Human Beings Following Total-body Hematological Studies on Patients Treated by Total-body Changes in Mean Blood Levels of Metallurgical Laboratory Employees during the First Year of Employment as By Norman Pearlman and G. A. Sacher Related to Working Conditions., .......................... 419 Biometric Investigations of Blood Constituents and Characteristics in a Population of Project Workers.. ................ 425 Effect of Exercise on Leucopenia: A Statistical Analysis.. .... 456

Page 7

Determination of Radium in Excreta.. ...................... 467 Treatment of Plutonium Poisoning by Metal Displacement .... 47’ By Jack Schubert Status of Health and Protection at the Hanford Engineer Tolerance to Whole-body Jrradiation of Patients with

Page 8

GENERAL INTRODUCTION TO REPORTS ON MEDICINE, HEALTH PHYSICS, AND BIOLOGY* Formerly AssociateeProject Director for Health From its inception, the Atomic Energy Project consisted of several individual projects; each had its own objectives, its own organization, and its own laboratories for research and development. A healthy rivalry existed among them; each hoped to be the first to reach its objectives. Their efforts were coordinated in the beginning by the Office of Scientific Research and Development and in the later stages by the Manhattan District of the U. S. Army Corps of Engineers. The group assigned to the pmblems of proving that a nuclear chain reaction could be achieved, of making a structure using this reaction to produce plutonium, and of developing a chemical process for isolating pure plutonium was established at the University of Chicago. For this purpose that university formed the Metallurgical Laboratory under the able leadership of Prof. Arthur H. Compton. Early in 1942 the scientists of the Metallurgical Laboratory became convinced thata nuclear chain-reactingpile could be built. They realized the enormity of the health hazards that such a unit would create. Some of them had friends or acquaintances who had been injured in experimental work with x-rays or with radium, and many were aware of the harmful effects suffered by some of the workers in the radium-dial industry. The exact nature and extent of the hazards to be encountered were not known. In general it was realized that the pile in which the chain reaction would take place would be a f a r greater source of fast and Slow neutrons and gamma rays than could have been dreamed possible earlier periods. It w a s estimated that the pieces of uranium that would have to be removed from the pile after fission had occurred 'Based on Univ. of Callf. Report NDP-48c.

Page 9

h e purpose of this investigation was to determine the clinical and atological effects upon human beings of daily repeated exposure e entire body to filtered high-voltage x-rays in the Heublein unit e Heublein unit delivers x-rays generated a t 180 to 185 kv, f i l - “e i n the other room. In either room the thicker filter provides 7 per hour while the thinner filter provides 1.65 r per hour. The vas requested that first some patients be treated with a dose of ier day for 30 days, then some at 15 r per day for 20 days, then, sible,some at 20 r per day for 15 days. This total dose of 300 r irbitrarily selected on the basis of previous experience, from to 1933 and from 1935 to 1942, with the Heublein unit. On the of that experience it was believed that 300 r could be tolerated course of treatment over a period of 10 to 30 days by individ1 good general condition and that it should be a sufficient dose Id some detectable effects on the blood count and to serve as a lo the clinical tolerance for whole-body irradiation.

Page 10

This was the most difficult part of the project, calling for lection of patients having metastatic cancer of such extent tribution a s to render their cases totally unsuitable for any ac method of surgical or radiological treatment, yet demanding th patients be in good enough general condition so that they might pected not only to tolerate the exposure to 300 r of total-body ir ation in a period of 10 to 30 days, but also to survive the co effects of their disease and the irradiation for at least six order that some conclusions might be drawn a s to the later It was recognized that none of the patients with 1 leukemias would be suitable for this project because of of the hematopoietic system in such cases both to i r r a various disorders incidental to the disease. Thus it was neces confine the selection to subjects with metastatic carcinomas astatic sarcomas other than of the lymphoid system. It was recognized, moreover, that in such advanced case ther progress of the malignant neoplastic process, if indeed i cause the death of the patient sooner than six months after body irradiation, would in any case be very likely to co interpretation of the clinical and hematological effects by reason either of changes in the patient's nutrition or tions attributable to the disease. However, it could be it were possible to show that no definite or marked harm patients a s sick as those to be chosen, it could certainly b that healthy persons should be able to tolerate the proje the Heublein unit there might nevertheless on further trial some beneficial clinical effect, offered justification, in a primary purpose, for undertaking the project. The hope that, despite the negative results obtained Carefully selected patients were admitted to where they received the prescribed daily dose of w tion day after day plete blood count, including a differential and platelet co every 2 to 4 days. Upon completion of the treatment as a rule able to go home at once and were then seen

Page 11

IRRADIATION MLERANCE OF ADVANCED CANCER PATIENTS 487 3m one to four weeks for clinical examination and blood counts f a r long a s possible following the treatment. Histories of patients treated between Dec. 18, 1942, and Aug. 29, 14, a r e summarized in Tables 10.1 to 10.9. I t was possible to see and obtain blood counts for a period longer in six months after treatment in only three Qf the eight cases. T w o ients (cases 2 and 3) were in such poor condition that it was nec- ;ary to discontinue the treatment when about half the projected dose been administered, and they died 71 and 49 days, respectively, 'r treatment was stopped, apparently because of progress of the ease and not as an effect of the irradiation. In case 1 the patient d at home one month after receiving the total exposure of 300 r, likewise apparently from progress of the disease. In the case of ;e three patients known to have died, permission for necropsy was, xtunately, not obtained. In cases 4 and 7 the duration of survival mknown, the patients having been observed for the last time a little -e than four months after having been exposed to 300 r (at 10 r day i n case 4,. and at 15 r per day in case 7); but in each of these cases the disease was rapidly becoming more advanced, and there no evidence that the downward course wasdue to any other factor 1 advance of cancer. 1 case 8, one of the three cases (cases 5, 6, and 8) that were fol- ?d for more than six months, the patient was failing rapidly, with nsive liver metastases when last observed, seven and a quarter iths after treatment. In case 5 the widespread male-breast carcia had beep growing slowly but steadily for a year following total- ' irradiatbn with 300 r at 10 r per day, and it was then decided .he sake of possible palliation to try orchiectomy, which seemed & h e r observation for an additional six months to have had some it palliative effect. In case 6 the patient was followed nineteen 'hs. From about eight to seventeen months after treatment he bedridden from progress of the disease and was considered terilly ill, escaping follow-up for a period of eleven months; but in the next two months he became ambulant again, went about 5 , and gained 25 lb. This improvement occurred despite roentgen nce of considerable increase in the bulk of numerous large mary metastases of mucoepidermoid carcinoma of the parotid. -med doubtful that the irradiation- of the entire body, with 300 r

Page 12

at 10 r per day given nineteen months previously, could responsible in any way for this improvement; and, per con a matter for speculation a s to whether the patient’s bedridden occurring for eight months following the irradiation and cau Table 10.1 -Patients Treated between Dec. 18,1942, and Aug. 29, no. Sex Age Diagnosis r/&Y r 1 M 31 Melanoma 10 300 Died at home 2 M 25 Teratoma testis, 10 150 Died in hospital, f+s3progress of disease,metastasis to lungs 3 M 44 Melanoma 10 161 Died a tho 4 F 52 Carcinomaof breast 10 300 Last seen 5 M 64 Carcinoma of male 10 300 Living18 mon carcinoma of parotid

Page 13

IRRADIATION TOLERANCE OF ADVANCED CANCER PATIENTS 489 IO may have benefited somewhat from an orchiectomy done one fter total-body irradiation. He suffered no such bedridden peilthough a man sixty-four years of age; the man who became r.arily bedridden was only thirty-three years old. On this slim . t might be surmised that the eleven-month period of disability ! 6 was not caused by the effects of radiation. Unfortunately no ounts were obtained in case 6 while the patient was confined to Table 10.2-Case 1, Age 31, Melanoma Died at home Case 1, Male, Age Thirty-one Years. Diagnosis: Melanoma of neck, with widespread cutaneous and subcutaneous metasOnly previous irradiation was eleven x-ray treatments to neck ionths before Heublein therapy. een Dec. 15, 1942, and Jan. 4, 1943, patient received 300 r at 10 r per day of Heublein treatment. ?g treatment no consistent changes were found in his blood although rather wide inconsistent variations were recorded. :ng treatment there was recorded after 8 days a drop in total :ells to 5,000 from a previous range of from 6,000 to 14,800, lrop in platelets to 138,000 from a previous range of from two subsequent counts, made 12 and 19 days following comof treatment, the white cells dropped further to 3,900 and

Page 14

day, the hemoglobin to 68 per cent, and the platelets to 77,000. In view of the fact that the patient died of his disease only 26 later it seems probable that these changes represented a ter depression due to the disease, rather than a result of irradiauo this case blood-chemistry determinations were made on serum rubin, serum total calcium, serum chlorides, serum cholestero Table 10.3-Case 2, A g e 25, Teratoma Teatls, Metastasis to Lungs 3/16/43 Dled In hospital; no post-mortem were found that seemed significant in relation to the radia testis, with metastasis to lungs. Only previous the chest, at another hospital. Between Dec. 21, 1942, and Jan. 14, 1943, patient r e was progressing rapidly and he was becoming anemic. T count had fallen from a pretreatment level of 4.14 mill about the accuracy of the last platelet count, however, s so much out of line with one of 223,000 taken four days one of 177,000 taken two days later. Moreover, the during the following 23 days ranged from 156,000 to 2

Page 15

IRRADIATION TOLERANCE OF ADVANCED CANCER PATIENTS 491 .reatment period of 23 days after further anemia developed (red , down to 2.6 million, hemoglobin to 52 per cent), and along with a mcy to a lower white cell count (to 6,200 from a previous range lout 8,100 to 9,200)there developed a lymphopenia (lymphocytes 9 to 1 per cent, contrasted with a previous range of from 10 to .rther blood-count observations are believed valueless in this ., since the patient was turned back tothe urology service because is unsuitability for continuation of Heublein treatment. He was Died at home Mise (1,OOO)Plat Retic Ret >n androgens for 20 days and soon afterward local x-ray therapy he chest. He died 71 days after Heublein treatment was discontin- . Necropsy was not permitted. n this case, as in case 1, chemical determinations showed no signted melanoma (origin undetermined; bulky left axillary metasta- , subcutaneous …