List of Attachments For Briefing Book Volume 2 Tab L Attachment 1: Applications For Research Contracts Attachment 2: Research Proposal For Sub-Task In Nuclear Weapons Effects Research, 5/8/61 Attachment 3: Metabolic Changes In Humans Following Total Body Irradiation Attachment 4: Letter to Faculty Committee on Research, From Ben Friedman, Eugene L. Saenger, The Therapeutic Effect Of Total Body Irradiation Followed By Infusion of Stored Autologous Marrow In Humans Attachment 5: Whole Body Radiation Study At the University of Cincinnati, By the Ad Hoc Committee of the University of Cincinnati, January 1972. Attachment 6: Radiation-Induced Urinary Excretion of Deoxycytidine by Rats and Humans by Wen Chen, James G. Kereiakes, Ben Friedman, Eugene Saenger. Attachment 7: Whole Body and Partial Body Radiotherapy Of Advanced Cancer, by Eugene Saenger, Edward B. Silberstein, Bernard Aron, Harry Horwitz, James G. Keriakes. RESEARCH AND DEVELOPMENT DIVISION WASHINGTON 25. D. C. APPLICATION FOR RESEARCH CONTRACT - PART 1 DO NOT WRITE IN THIS SPACE NEW RENEWAL CONTRACT NUMBER 1. TITLE OF PROJECT Metabolic changes in Humans following Total Body Radiation 2. DATE RESEARCH CONTRACT TO BEGIN 1 February 1959 3. NAME AND OFFICIAL POSITION OF RESPONSIBLE INVESTIGATOR Eugene L. Saenger, M.D. Associate Clinical Professor of Radiology 4. DATE OF APPLICATION 25 September 1958 5. PRINCIPAL PROFESSIONAL ASSISTANT (s) George M. Guest, M.D., Professor of Research Pediatrics Helen K. Dorry, M.A., Research Associate, Children's Hospital Research Foundation Harold Perry, M.D., Assistant Professor of Radiology 6. OTHER PROJECTS IN WHICH YOU ARE PARTICIPATING AND SOURCE OF SUPPORT (Other government contracts or funds from civilian foundations, etc.) a) Incidence of Neoplasia in Irradiated Children; supported by National Institute of Health, P.H.S., C-2973 b) Preparation of Handbook on Medical Aspects of Radiation Accidents, supported by U.S. Atomic Energy Commission, contract no. AT(001-1)-2166 7. NAME AND LOCATION OF INSTITUTION WHERE WORK WILL BE PERFORMED Department of Radiology, University of Cincinnati, College of Medicine, Cincinnati, Ohio SIGNATURE OF RESPONSIBLE INVESTIGATOR____________________________ 8. APPLICATION APPROVED BY OFFICIAL AUTHORIZED TO SIGN FOR INSTITUTION NAME PRINTED OR TYPED Stanley D, Dorst, M.D. SIGNATURE OFFICIAL TITLE Dean, College of Medicine INSTITUTION University of Cincinnati 9. APPLICATION APPROVED BY HEAD OF DEPARTMENT WHERE WORK IS TO BE PERFORMED NAME PRINTED OR TYPED Benjamin Pelson, M.D. SIGNATURE OFFICIAL TITLE Professor of Radiology and Head of Department of Radiology OTSG FORM 108 1 Nov 57 PREVIOUS EDITIONS OF THIS FORM MAY BE USED Form Approved Budget Bureau No. 49-R344 DEPARTMENT OF THE ARMY OFFICE OF THE SURGEON GENERAL RESEARCH AND DEVELOPMENT DIVISION WASHINGTON 25 D.C. APPLICATION FOR RESEARCH CONTRACT - PART III TITLE OF PROJECT Metabolic Changes in Humans Following Total Body Radiation RESEARCH PLAN (Include background, specific aims, methods of procedure in detail, significance of this research. Use additional pages if necessary.) 3. Scientific background. Several reports have described changes in nitrogen metabolism following irradiation (1, 2, 3). All have shown increase in nitrogen excretion following total body irradiation to various laboratory animals. Mefford and Martens (4) have studied amino-aciduria by paper chromatography in rats. Katz and Hasterlik (5), and Hempelmann, Lisco and Hoffman (6) have studied amino-aciduria following radiation in humans by means of paper chromatography. Hempelmann, et al, found amino-aciduria in 3 of their 9 cases. Katz and Hasterlik reported increases of as high as ten times normal values of total daily amino acid excretion in 4 patients. Quantities of individual amino acids excreted varied from 2- 20 times normal values. Abnormal values were found as early as 12 hours following exposure, and increases levels persisted for as long as 5 months. No direct quantitative relation to radiation dose could be established. These findings suggest that amino-aciduria may serve as an indicator of the biological response of humans to irradiation. The reports of amino-aciduria in humans have described the findings in individual exposed in reactor accidents (3,6) and no control measurements were possible. The proposed investigation will include studies of amino-acid excretion before and after irradiation both to the whole body and to portions of the body. The urinary excretion of amino acids will be measured both by paper chromatography and total amino acid nitrogen in order to find a relatively simple technique for biological effects of radiation. Significant increases in total amino acids and individual amino acids will be sought. The amino acid levels will be compared to levels of creatine (10) and urea (11). These studies will be valuable in the understanding of the mechanisms of amino-aciduria. Preliminary studies by our group have demonstrated that transient amino-aciduria will also occur with extensive surgical procedures and with infection. Studies of 5 patients exposed at the Y-12 accident at Oak Ridge in June 1958 showed elevated excretion of beta aminoisobutyric acid with levels related to the total dose received by the individual. 4. Scientific Scope of the Proposed Research Amino-aciduria following irradiation has been reported in humans and animals. The purposes of this investigation is to study this (3) OTSG FORM 108b 1 Nov 57 Previous editions of this form may be used. Form Approved Budget Bureau No. 49-R344 DEPARTMENT OF THE ARMY OFFICE OF THE SURGEON GENERAL RESEARCH AND DEVELOPMENT DIVISION WASHINGTON 25. D. C. APPLICATION FOR RESEARCH CONTRACT - PART III TITLE OF PROJECT Metabolic Changes in Humans Following Total Body Irradiation RESEARCH PLAN (Include background, specific aims, methods of procedure in detail, significance of this research. Use additional pages if necessary.) phenomenon to elucidate some of the mechanisms responsible for amino-aciduria and to determine whether it is a practical biological test of radiation exposure. The Design of the Proposed Research is as follows: 1. Comparison of techniques for determination of urinary amino acids by the Van Slyke and chromatographic techniques. 2. Determination of excretion of urinary amino acids atvarious dosages of total body irradiation. 3. A study of the effects of partial versus total body irradiation on urinary amino acid excretion. 4. Studies of the immune mechanisms of humans receivingtotal body irradiation. Selection of Patients Patients for total body irradiation will be limited to adult males who have proven metastatic malignancy but are in good nutritional state. The studies will be limited to males because of the variations in amino-aciduria found with the menstrual cycle in women. These patients will be used for parts 1 and 2. In part 3 male patients who are receiving radiation therapy for neoplasias will also be included. Except in special cases as noted below, patients with lymphomaswill not be used in these studies. All patients will be hospitalized at the Cincinnati General Hospital. They will have histories, physical examinations, routine hematological and urine studies and other laboratory studies as needed. Factors for irradiation as follows: Westinghouse Quadracondex constant potential therapy unit 250 KV, 15 Ma, filtration 2.0 mm Cu + 1 mm Al., H.V.L. 2.0 mm Cu.IOD 200 cm. Also total body irradiation will be carried out with Cobalt 60 teletherapy. Measurements will be checked by the Victoreen condenser r-meter and calibrated Dendix dosimeters using masonite and water phantoms. The technique of irradiation will be similar to that of Sinclair & Cole (12). Urine Studies Part 1. Comparison of paper Chromatography and Total Amino acid Nitrogen Two groups of 6 adult males will receive 50 r of total body irradiation in a single dose. Group A will consist of patients with relatively radio-resistant lesions Form Approved Budget Bureau No. 49-R344 DEPARTMENT OF THE ARMY OFFICE OF THE SURGEON GENERAL RESEARCH AND DEVELOPMENT DIVISION WASHINGTON 25. D. C. APPLICATION FOR RESEARCH CONTRACT - PART III TITLE OF PROJECT Metabolic Changes in Humans Following Total Body Irradiation RESEARCH PLAN (Include background, specific aims, methods of procedure in detail, significance of this research. Use additional pages if necessary.) stomach, bowel, brain) and Group B of patients with highly radio- sensitive tumors (lymphomas). Prior to irradiation urines will be collected for several days to serve as controls. All urines will be collected for 24 hour periods. An ------- from the early morning fastings sample will be refrigerated and the remainder pooled with the 24 hour urine below. The voidings will then be collected, refrigerated, pooled and frozen for the 24-hour periods. All samples will be analyzed in triplicate by both techniques for fasting and pooled values. If the initial fasting specimen provides enough data, the test can be simplified. Total urinary amino acids will be determined by the method of Van Slyke, MacPayden and Hamilton (7). Two dimensional paper partition chromatography will be carried out according to the methods of Block, ---------------. The 24 hour urines will be analyzed for uric acid, urea creatine, creatine and total nitrogen. An attempt will be made to maintain the patients in approximately the same nitrogen equilibrium. The values obtained by the two methods will be compared by analysis of variance and by determination of regression coefficients of the values of the Van Slyke method versus those of chromatography. In addition comparison of amino acid excretion in patients with known destruction of large tissues of tumor (Group B) can be compared to those in whom such a phenomenon is unlikely (Group A). Part 2. Determination of Excretion of Urinary Amino Acids at Various Dosages of Total Body Irradiation Patients to be studied will include those individuals with metastatic neoplasms and also patients who are receiving therapy in an attempt to cure or palliate various neoplasms. Patients in this study will not have had previous irradiation so as to avoid carry-over effects. In the initial selection of patients the group of patients with metastatic neoplasms cannot be selected at random from a normal population for inclusion in the study since normal individuals cannot be given total body irradiation. Selection criteria are as follows: 1. Patient to have proven diagnosis of neoplasm. 2. Patient to have proven -------------- 3. Patient to be in satisfactory nutritional state. Form Approved Budget Bureau No. 49-R344 DEPARTMENT OF THE ARMY OFFICE OF THE SURGEON GENERAL RESEARCH AND DEVELOPMENT DIVISION WASHINGTON 25. D. C. APPLICATION FOR RESEARCH CONTRACT - PART III TITLE OF PROJECT Metabolic Changes in Humans Following Total Body Irradiation RESEARCH PLAN (Include background, specific aims, methods of procedure in detail, significance of this research. Use additional pages if necessary.) The patients will be selected for three subgroups of total body irradiation by randomization. Subgroup A will serve as controls and will have all procedures carried out except that they will receive sham irradiation only. Subgroup B will receive 25 r and Subgroup C will receive 50 r. Each group will consist of 4 patients. The mean values of total amino acids in the urine of the three groups will be tested for significant differences by analysis of variance. Subgroup A will be tested against Subgroup C. Further groups will be studied at 100 r and 200 r. If there is no significant difference between B and C, then additional subgroups will be studied at exposures of 0, 5, 10, and 20 r of total body irradiation. One of the possible reasons that a relation between radiation exposures and amino acid excretion may reach a plateau value below 25 r of total body irradiation. It is for this reason that these additional groups may require study. Patients will be placed in these several groups by the same technique of randomization as described above. Another group of sham irradiated controls will be provided in order not to lose independence of comparisons. At the conclusion of these studies further analysis of the data will be carried out with calculations based on the integral dose received by each patient. The dosage response relationship will then be determined. Part 3. Study of the Effects of Partial versus Total Body Irradiation on Urinary Amino Acid Excretion After suitable base line values are established as described in Part 2, further studies will be carried out in order to compare total body irradiation with doses of localized irradiation to give equal integral dosage. For example, if a patient receives total body irradiation with an integral dose of 50,000 gram roentgens, his amino-aciduria will be compared with that of an individual who has received an equal integral dose with all irradiation given to a localized region of the body. One group of patients will receive the dose to the upper abdomen, another group to the chest, another group to the head and neck. These patients will have determinations of urinary amino acids before receiving radiation and will be followed afterwards for a period of one to three years. The first group to be studied will be those patients who received localized irradiation to the kidneys and liver. Since irradiation to either of those organs (6) Form Approved Budget Bureau No. 49-R344 DEPARTMENT OF THE ARMY OFFICE OF THE SURGEON GENERAL RESEARCH AND DEVELOPMENT DIVISION WASHINGTON 25. D. C. APPLICATION FOR RESEARCH CONTRACT - PART III TITLE OF PROJECT Metabolic Changes in Humans Following Total Body Irradiation RESEARCH PLAN (Include background, specific aims, methods of procedure in detail, significance of this research. Use additional pages if necessary.) may provide a mechanism for amino-aciduria (see Part 1) it will be valuable to determine the levels of amino-aciduria following this type of irradiation. It must be recognized that in applying radiation to the human it is not possible to irradiate the liver without irradiating the kidneys and conversely one cannot irradiate the kidneys without irradiating the liver. If the amino-aciduria is of the same order of magnitude as that found with total body irradiation, it will suggest that irradiation of either of both of the organs is responsible for those findings. The second group to be studied are those individuals receiving localized radiation to the chest. If the amino-aciduria approaches levels equal to those found with total body irradiation in comparable integral doses, increased tissue breakdown should be suspected. From a practical viewpoint those two groups will be studied simultaneously depending upon clinical material available on the Tumor Service of the Cincinnati General Hospital. Part 4. In cooperation with Dr. A.J. Luzzio of the Radiobiology Department, U.S. Army Medical Research Laboratory, Ft. Knox, KY, we shall supply blood semen samples from all patients irradiated as described previously. Samples will be obtained just prior to irradiation, just after irradiation and ten days after irradiation. They will be sent to Dr. Luzzio for his studies. REFERENCES (7) Form Approved Budget Bureau No. 49-R344 DEPARTMENT OF THE ARMY OFFICE OF THE SURGEON GENERAL RESEARCH AND DEVELOPMENT DIVISION WASHINGTON 25. D. C. APPLICATION FOR RESEARCH CONTRACT - PART IV BIOGRAPHY (Biographical sketches required on responsible investigator and principal professional assistants only. If this is a request for renewal utilizing essentially the same personnel as previously, biographical sketches will not be necessary.) 1. NAME Eugene L. Saenger, M.D. 2. ADDRESS Radioisotope Laboratory, Cincinnati General Hospital, Cincinnati 29, Ohio 3. AGE 41 4. EDUCATIONAL BACKGROUND (College and/or University) Harvard College A.D., cum laude Biochemical Sciences 1938 University Cincinnati, College of Medicine, M.D. 1942 5. RESEARCH TRAINING (List of institutions, research director, subject and dates) Interne General Hospital, Cincinnati 1942-1943 Resident in Radiology, General Hospital 1943-46 Chief Radioisotope Unit, Brooke Army Hospital, ---- 1954-55 Consultant Surgical Research Unit 1954-55 Director, Radioisotope Laboratory, Univ. of Cinti., Coll. of Medicine 1958 Assistant Professor of Radiology ---- Assoc. Clinical Professor of Radiology 1957- Consultant Brooke Army Unit Hospital 1956- 6. OTHER INFORMATION BEARING ON QUALIFICATIONS (Hospital appointments, professional societies, specialty board, etc.) Attending Radiologist, Cincinnati General Hospital; Radiation Therapist Children's Hospital, Cincinnati, Ohio; Diplomate, American Board of Radiology, Member American ------- Society, Radiological Society of North America, Health Physics Society; Alpha Omega Alpha 7. BIBLIOGRAPHY (Do not list more than ten publications) 1.Saenger, E.L., et al, Emergency pleasures and precautions in Radium accidents. Jour. Med. Assn. 149:313-315 June 23, 1952. 2. Results of Therapy with Radioactive Iodine-131 in Hyperthyroidism. Ohio State Med. Jour. 50:26-27, Jan 1954. E.L. Saenger, et al.3. Saenger, E.L., et al, Letterer ---- Disease. Problems in Diagnosis and Treatment, Amer. Jour. Roent, Med. Therapy & Nucl Med, L I, No. 3, Journal Med. Bureau of Standards Handbook 4. UNREADABLE TEXT 5. 6. 7. 8. 9. 10. Anderson, D.R. Effects of Radiation on Creatine Metabolism. Radiation Research ----- (1957) 11. Kay, R.N., Early, J.C. and Entenman, C. Radiation Research6: 98-189 (1957) 12. Sinclair, W.M. and Cole, A. Technique and dosimetry for whole body x-radiation of patients. USAF Report No. 57-70 Mar. 1957. Form Approved Budget Bureau No. 49-R344 DEPARTMENT OF THE ARMY OFFICE OF THE SURGEON GENERAL RESEARCH AND DEVELOPMENT DIVISION WASHINGTON 25. D. C. APPLICATION FOR RESEARCH CONTRACT - PART IV BIOGRAPHY (Biographical sketches required on responsible investigator and principal professional assistants only. If this is a request for renewal utilizing essentially the same personnel as previously, biographical sketches will not be necessary.) 1. NAME Guest, George Martin, M.D. 2. ADDRESS Children's Hospital Research Foundation, Cincinnati 29, Ohio 3. AGE 60 4. EDUCATIONAL BACKGROUND (College and/or University) Ohio Wesleyan University, Delaware, Ohio 1916-18 University of Cincinnati, B.S. 1920 University of Cincinnati, College of Medicine M.D. 1922 University of Cincinnati, College of Medicine M.S. 1923 5. RESEARCH TRAINING (List of institutions, research director, subject and dates) Cincinnati General Hospital, Resident in Pathology and Instructor Pathology 1922-1923 Institut Pasteur, Brussels, Belgium, Fellow of the Commission for Relief in Belgian Educational Foundation 1923-1925 Boston Children's Hospital, Intern in Pediatrics, Resident Bacteriologist and Ass't in Bacteriology, Harvard Medical School 1926-1927 University of Cincinnati, College of Medicine, Dept. of Pediatrics: Ass't Prof. University of Cincinnati, College of Medicine, Prof. of Research Pediatrics. 6. OTHER INFORMATION BEARING ON QUALIFICATIONS (Hospital appointments, professional societies, specialty board, etc.) 7. BIBLIOGRAPHY (Do not list more than ten publications) 1. Gaest, G.M., et al, Centrinage method for the determination of the volume of cells in blood, J. Lab & Clin. Med. 19:757-767, April 1934.2. Guest, G.M., et al, Hematologic Methods in detecting nutritional anemia, in Nuturition: The newer diagnostic methods, 17th ann. conf., Milbank Memorial Fund pp. 133-165, 1938 3. Guest, G.M. et al, Organic acid-soluble phosphorus compounds of the blood. Physial. Rev. 21:410-437, July 1941. 4. Guest, G.M., et al, Diabetic coma: Metabolic derangements and principles for corrective therapy, Am. J. Med. 7: 633-646, 1949. 5. Guest, G. M. et al, Urinary excretion of amino-acids during alloga-induced diabetes in rats, Proc. Soc. Impor. Biol. & Med. 71:410-412, 1949. 6. UNREADABLE TEXT 7. 8. SG FORM 108C 1 APR 54 Form Approved Budget Bureau No. 49-R344 DEPARTMENT OF THE ARMY OFFICE OF THE SURGEON GENERAL RESEARCH AND DEVELOPMENT DIVISION WASHINGTON 25. D. C. APPLICATION FOR RESEARCH CONTRACT - PART IV BIOGRAPHY (Biographical sketches required on responsible investigator and principal professional assistants only. If this is a request for renewal utilizing essentially the same personnel as previously, biographical sketches will not be necessary.) 1. NAME Helen K. Berry 2. ADDRESS Children's Hospital Research Foundation, Cincinnati 29, Ohio 3. AGE 33 4. EDUCATIONAL BACKGROUND (College and/or University) University of Texas, M.A. 1949 5. RESEARCH TRAINING (List of institutions, research director, subject and dates) Research Scientist, Biochemical Institute, University of Texas 1947-53 6. OTHER INFORMATION BEARING ON QUALIFICATIONS (Hospital appointments, professional societies, specialty board, etc.) Research Associate - Children's Hospital Research Foundation American Association for the Advancement of Science Sigma Xi 7. BIBLIOGRAPHY Individual Metabolic Patterns and Human Disease with Dr. R.J. Williams, also other articles on technique of paper chromatography. OTSG FORM 108C 1 Nov 57 Previous editions of this form may be used. Form Approved Budget Bureau No. 49-R344 DEPARTMENT OF THE ARMY OFFICE OF THE SURGEON GENERAL RESEARCH AND DEVELOPMENT DIVISION WASHINGTON 25. D. C. APPLICATION FOR RESEARCH CONTRACT - PART I 1. TITLE OF PROJECT Metabolic Changes in Humans following Total Body Radiation 3. NAME AND OFFICIAL POSITION OF RESPONSIBLE INVESTIGATOR Eugene L. Saenger, M.D., Associate Clinical Professor of Radiology 5. PRINCIPAL PROFESSIONAL ASSISTANT (s) George M. Guest, M.D., Professor of Research Pediatrics Helen K. Berry, M.A., Research Associate, Children's Hospital Research Foundation Harold Perry, M.D., Assistant Professor of Radiology 6. OTHER PROJECTS IN WHICH YOU ARE PARTICIPATING AND SOURCE OF SUPPORT (Other government contracts or funds from civilian organizations) a) Incidence of Neoplasia in Irradiated Children; supported by National -----of Health, P.H.S., C-2973 b) Preparation of Handbook on Medical Aspects of Radiation Accident Appt. by U.S. Atomic Energy Commission, contract no. AT(30-1)----- 7. NAME AND LOCATION OF INSTITUTION WHERE WORK WILL BE PERFORMED Departments of Radiology, University of Cincinnati, College of Medicine, Cincinnati, Ohio SIGNATURE OF RESPONSIBLE INVESTIGATOR_________________________ 8. APPLICATION APPROVED BY OFFICIAL AUTHORIZED TO SIGN FOR INSTITUTION NAME PRINTED OR TYPED Stanley E. Dorst, M.D. SIGNATURE OFFICIAL TITLE Dean, College of Medicine INSTITUTION University of Cincinnati 9. APPLICATION APPROVED BY HEAD OF DEPARTMENT WHERE WORK IS TO BE PERFORMED NAME PRINTED OR TYPED Benjamin Felson, M.D. SIGNATURE OFFICIAL TITLE Professor of Radiology and Head of Department of Radiology OTSG FORM 108 1 Nov 57 PREVIOUS EDITIONS OF THIS FORM MAY BE USED. DEPARTMENT OF THE ARMY OFFICE OF THE SURGEON GENERAL RESEARCH AND DEVELOPMENT DIVISION WASHINGTON 25, D.C. APPLICATION FOR RESEARCH CONTRACT - PART II Metabolic changes in Humans following Total Body Radiation REQUIREMENTS Budget Requested (from office of the Other Surgeon Gen.) Sources 1. Personnel (list positions, salaries, and names of professional personnel, if known) Technician (full time) $4400.00 Technician (full time) 4000.00 Physicist (part time) 1000.00 Univ. Cin. Clinician (part time) 2000.00 " " Statistician (part time) 1000.00 " " Secretary (part time) 1500.00 " " total $13,900.00 2. Equipment (Itemize) Remodeling of laboratory room $900.00 Densitometer and filters $460.00 Ultraviolet lamp $100.00 Centrifugal Chromatograph $250.00 Freeze drying apparatus & Vacuum pump $200.00 Refrigerator $250.00 Spray equipment $150.00 VanSlyke apparatus $350.00 Chromatographic columns $200.00 Colorimeter $450.00 total $3,310.00 3. Consumable supplies (itemize) Miscellaneous glassware & micropipettes $ 570.00 Chemicals, chromatography paper & supplies$1740.00 Phantoms, etc. $ 200.00 $2510.00 4. Travel (State Purpose) Conferences and scientific meetings $500.00 5. Sub-total $20,220.00 6. Overhead (established by official auditors with concurrence of institution or research agency and contracting officer, and may be based upon percentage of total salaries and wages, or percentage of total cost of the project. Indicate below. Provisional 35% of salaries $4,865.00 X percent of salaries and wages Percent total cost 7. Total budget $25,085.00 Estimate of Future Requirements (To be filled out only if type of project indicates that it will continue for more than a year) First additional year $21,775.00 Second additional year $21,775.00 Other sources from the school, other contracts, other government agencies, foundations, etc. OTSG Form 1 Nov 67 Previous editions of this form may be used Department of the Army Office of the Surgeon General Research and Development Division Washington 25, D.C. Application for Research Contract Part III Title of Project Metabolic Changes in Humans Following Total Body Radiation Research Plan (include background, specific aims, methods of procedure in detail, significance fo this research. Use additional page, if necessary.) elucidate some of the mechanisms responsible for amino-aciduria and to determine whether it is a practical biological test of radiation exposure The Design of thc proposed Research is as follows: 1. Comparison of techniques for determination of urinary amino acids by the Van Slyke and chromatographic techniques. 2. Determination of excretion of urinary amino acids at various dosages of total body irradiation. 3. A study of the effects of partial versus total body irradiation on urinary amino acid excretion. 4. Studies of the immune mechanisms of humans receiving total body irradiation Selection of Patients Patients for total body irradiation will be limited to adult males who have proven metastatic malignancy but are in good nutritional state. The studies will be limited to males because of the variations in amino-aciduria found with the menstrual cycle in women. These patients will be used for parts 1 and 2. In Part 3 male patients who are receiving radiation therapy for neoplasms will also be included. Except in special cases as noted below, patients with lymphomas will not be used in these studies. All patients will be hospitalized at the Cincinnati General hospital. They will have histories, physical examinations, routine hematological and urine studies and other laboratory studies as needed. Factors for irradiation are as follows: Westinghouse Quadrocondex constant potential therapy unit 250 KV, 15 Ma, filtra 2.0 mm Cu +1 mm Al., H.V.L. 2.0 mm Cu. TSD 200 cm. Also total body irradiation will be carried out with Cobalt 60 teletherapy. Measurements will be checked by the Victoreen condenser r-meter and calibrated Bendix dosimeters using masonite and water phantoms. The technique of irradiation will be similar to that of Sinclair & Cole (12). Urine Studies Part l. Comparison of paper Chromatography and Total Amino Acid Nitrogen Techniques. Two groups of 6 adult males will receive 50 r of total body radiation in a __dose. Group A will consist of patients with relatively radio-resistant lesions (4) Department of the Army Office of the Surgeon General Research and Development Division Washington 25, D.C. Application for Research Contract Part III Title of Project Metabolic Changes in Humans Following Total Body Radiation Research Plan (include background, specific aims, methods of procedure in detail, significance of this research. Use additional pages, if necessary.) stomach, bowel, brain) and Group B of patients with highly radio- sensitive tumors (lymphomas). Prior to irradiation urines will be collected for several days to serve as controls. All urines will be collected for 24 hour periods. An aliquot from the early morning fasting sample will be refrigerated and the remainder pooled with the 24 hour urine below. The voidings will then be collected, refrigerated, pooled arid frozen for the 24-hour periods. All samples will be analyzed in triplicate by both techniques for fasting and pooled values. If the initial fasting specimen provides enough data, the test can be simplified. Total urinary amino acids will be determined by the method of Van Slyke, MacFayden and Hamilton (7). Two dimensional paper partition chromatography will be carried out according to the methods of Block, Durrum and Zweig (9). The 24 hour urines will be analyzed for uric acid, urea creatinine, creatinine and total nitrogen. An attempt will be made to maintain the patients in approximately the same nitrogen equilibrium. The values obtained by the two methods will be compared by analysis of variance and by determination of regression coefficients of the values of the Van Slyke method versus those of chromatography. In addition comparison of amino acid excretion in patients with known destruction of large masses of tumor (Group B) can be compared to those in whom such a phenomenon is unlikely (Group Part 2. Determination of Excretion of Urinary Amino Acids at various Dosages of Total Body irradiation Patients to be studied will include those individuals with metastatic neoplasms and also patients who are receiving radiation therapy in an attempt to cure or palliate various neoplasms. Patients in this study will not have had previous irradiation so as to avoid carry-over effects. In the initial selection of patients the group of patients with metastatic neoplasms cannot be selected at random from a normal population for inclusion in the study since normal individuals cannot be given total body radiation. Selection criteria are as follows: 1. Patient to have proven diagnosis of neoplasm. 2. Patient to have proven evidence of metastasis. 3. patient to be in satisfactory nutritional state. (5) Department of the Army Office of the Surgeon General Research and Development Division Washington 25, D.C. Application for Research Contract Part III Title of Project Metabolic Changes in Humans Following Total Body Radiation (Include background, specific aims, methods of procedure in detail, significance of this research. Use additional pages, if necessary.) The patients will be selected for three subgroups of total body irradiation by randomization. Subgroup A will serve as controls and will have all procedures carried out except that they will receive sham irradiation only. Subgroup B will receive 25 r and Subgroup C will receive 50 r. Each group will consist of 4 patients. The mean values of total amino acids in the urine of the three groups will be tested for significant differences by analysis of variance. Subgroup A will be tested against Subgroups B and C. Also Subgroup B will be tested against Subgroup C. Further groups will be studied at 100 r and 200 r. If there is no significant difference between B and C, then additional subgroups will be studied at exposures of 0,5,10 and 20 r of total body irradiation. One of the possible reasons that a relation between radiation exposure and amino acid excretion may reach a plateau value below 25 r of total body irradiation. It is for this reason that these additional groups may require study. Patients will be placed in these several groups by the same technique of randomization as described above. Another group of sham irradiated controls will be provided in order not lose independence of comparisons. At the conclusion of these studies further analysis of the data will be carried out with calculations based on the integral dose received by each patient. The dosage response relationship will then be determined. Part 3. Study of the Effects of Partial versus Total Body irradiation on Urinary Amino Acid Excretion After suitable base line values are established as described Part 2, further studies will be carried out in order to compare total body irradiation with doses of localized irradiation to give equal integral dosage. For example, if a patient receives total body irradiation with an integral dose of 50,000 gram roentgens, his amino-aciduria will be compared with that of an individual who has received an equal integral dose with all irradiation given to a localized region of the body. One group of patients will receive the dose to the upper abdomen, another group to the chest, another group to the head and neck. These patients will have determinations of urinary amino acids before receiving radiation and will be followed afterwards for a period of one to three years. The first group to be studied will be those patients who receive localized irradiation to the kidneys and liver. Since irradiation to either of these organs (6) Department of the Army Office of the Surgeon General Research and Development Division Washington 25, D.C. Application for Research Contract Part III Title of Project Metabolic Changes in Humans Following Total Body Radiation (Include background, specific aims, methods of procedure in detail, significance of this research. Use additional pages, if necessary.) may provide a mechanism for amino-aciduria (see Part l) it will be valuable to determine the levels of amino-aciduria following this type of irradiation. It must be recognized that in applying radiation to the human it is not possible to irradiate the liver without irradiating the kidneys and conversely one cannot irradiate the kidneys without irradiating the liver. If the amino-aciduria is of the same order of magnitude as that found with total body irradiation, it will suggest that irradiation of either or both of the organs is responsible for these findings. The second group to be studied are those individuals receiving localized radiation to the chest. If the amino-aciduria approaches levels equal to those found with total body irradiation in comparable integral doses, increased tissue breakdown should be suspected. From a practical viewpoint these two groups will be studied simultaneously depending upon clinical material available on the Tumor Service of the Cincinnati General Hospital. Part 4. In cooperation with Dr. A.J. Luzzio of the Radiobiology Department, U.S. Army Medical Research Laboratory. Ft. Knox, Ky. we shall supply blood serum samples from all patients irradiated as described previously. Samples will be obtained just prior to rradiation, just after irradiation and ten days after irradiation. They will be sent to Dr. Luzzio for his studies. REFERENCES l. Brues, A., Nuclear Science Abstracts, 7:7, 1953. 2. Gustafson,G.E., and Koletsky, S., Am. J. Physiol. 171:319(1952). 3 White, J., Burr, B.E., and Stander. Argonne National Laboratory Quarterly Report, Feb.Mar.April 1952, 4794. 4. Mefford, R.B. and Martens,H.H., Science, 122:829, (1955). 5. Katz, E.J. and Hasterlik, R.S. , J. National Cancer Inst. 15:1085 (1955). 6. Hemplemann, L.H. and Hoffman, J.D., Ann. Int.Med. 36:Z79 (1952) 7. Van Slyke,D.D., MacFayden,D.A. and Hamilton, P.B. J. Biol.Chem. 150: 251, (1943). 8. Moore, S. and Stein. W.H., J. Biol. Chem. 211: 907 (1954). 9. Block. R.J., Durrum, E.L. and Zweig, G., A Manual of Paper Chromatography and Paper Electrophoresis, Academic Press, Inc., New York 1955. (7) Department of the Army Office of the Surgeon General Research and Development Division Washington 25, D.C. Application for Research Contract Part III Title of Project Metabolic Changes in Humans Following Total Body Radiation (Include background, specific aims, methods of procedure in detail, significance of this research. Use additional pages, if necessary.) 10.Anderson. D. R. Effects of Radiation on Creatine Metabolism. Radiation Research 7:300 (1957) 11.Kay, R.E., Early, J.C. and Entenman, C. Radiation Research 6:98-109 (1957) 11.Sinclair. W.K. and Cole. A., Technique and dosimetry for whole body x-irradiation of patients. USAF Report No. 57-70 Mar. 1957. (8) Department of the Army Office of the Surgeon General Research and Development Division Washington 25, D.C. Application for Research Contract Part IV Biography (Biographical sketches required on responsible investigator and principal professional assistants only. If this is a request for renewal utilizing essentially the same personnel as previously, biographical sketches will not be necessary) 1. Name 2. Address 3.Age Eugene L. Saenger, M.D. Radioscope Laboratory, 41 Cincinnati General Hospital, Cincinnati 29, Ohio 4. Educational Background (College and/or University) Harvard College A. B., cum laude Biochemical Sciences 1938 University Cincinnati, College of Medicine, M.D. 1942 5. Research Training (list of institutions, research director, subject and dates) Interne General Hospital, Cincinnati 1942-1943 Resident in Radiology. General Hospital 1943-46 Chief Radioisotope Unit. Brooke Army Hospital, FSHT 1954-55 Consultant Surgical Research Unit 1954-55 Director,Radioisotope Laboratory, Univ. of Cinti. Coll. of Medicine 1950- Assistant Professor of Radiology 1949-57 Assoc. Clinical Professor of Radiology 1957- Consultant Brooke Army Hospital 1956- 6. Other information bearing on qualifications (hospital appointments, professional societies, specialty board, etc) Attending Radiologist. Cincinnati General Hospital; Radiation Therapist Children's Hospital, Cincinnati, Ohio; Diplomate, American Board of Radiology, Member American Roentgen Ray Society Radiological Society of North America, Health Physics Society, Alpha Omega Alpha 7. Bibliography (Do not list more than ten publications) 1. Saenger. E.L. ,et al, Emergency Measures and precautions in Radium accident Jour.Med. Assn. 149:813-815 June 28, 1952. 2. Results of Therapy with Radioactive Iodine-131 in Hyper- thyroidism. Ohio State. Jour. 50:26-27, Jan 1954. E.L. Saenger, et al.3. Saenger, E.L. et al, Letterer-Siwe's Disease. Problems in Diagnosis and Treatment. Amer. Journ Roent, Rad. Therapy & Nucl Med. LXXI. No. 3a March 19__. 4. Protection against radiations from radium, cobalt-60. and cesium-137; National Bureau of Standards Handbook 54, section 9 accidents entailing radiation hazards. Sept. 1954. Saenger. E.L. et al.5. Saenger, E.L. et al, Carcinoma of the Prostate; Therapy with Radioactive Col gold. U.S. Armed Forces Med. Jour. VII.469 (April 1956).6. A Method for Monitoring background by means of a statistical control chart. Th Amer.Jour.Roent. Rad.Therapy & Nuc. Med. LXXV June 1956. 7. Saenger, E.L., et al, A method for labeling the lone star tick with radioactive indicator (p-32). Jour. of Economic Entomology 49-393, June 1956. 8. Radiation Hazards in the practice of surgery. The Am. surgeon. 22:676, 1956 9. Saenger, E.L. et al. Radium capsules and their assoc. hazards. Am. Jour. Roent. 77:511, March 1___. Department of the Army Office of the Surgeon General Research and Development Division Washington 25, D.C. Application for Research Contract Part IV Biography (Biographical sketches required on responsible investigator and principal professional assistants only. If this is a request for renewal utilizing essentially the same personnel as previously, biographical sketches will not be necessary) 1. Name 2. Address 3.Age Guest, George Martin. M.D. Children's Hospital Research 60 Foundation, Cincinnati 29, Ohio 4. Educational background (College and/or University) Ohio Wesleyan University, Delaware, Ohio 1916-18 University of Cincinnati. B.S. 1920 University of Cincinnati College of Medicine M.D. 1922 University of Cincinnati M. S. 1923 5. Research Training (list of institutions, research director, subject and dates) Cincinnati General Hospital, Resident in Pathology and Instructor Pathology 1922-19 Institut Pasteur, Brussels, Belgium, Fellow of the Commission for Relief in Belgium Educational Foundation 1923-1925 Boston Children's Hospital, Intern in Pediatrics, Resident Bacteriologist and Ass't in Bacteriology, Harvard Medical School 1926-1927 Univ. of Cincinnati, Coll. of Medicine, Dept. of Pediatrics Univ. of Cincinnati, Ass't Prof. 1928 Univ. of Cincinnati Assoc. Prof. 1935 Univ. of Cincinnati Prof. of Research Pediatrics 1947 6. Other information bearing on qualifications (hospital appointments, professional societies, specialty board, etc) Am. Pediatric Soc. (Member of Council; Chairman 1953) Alpha Omega Alpha Soc. for Pediatric Research (President 1942) Sigma Xi Am. Soc. of Biological Chemists Certified Licentiate of the Am. Board of Pediatrics 1936 Editorial Board Diabetes 7. Bibliography (Do not list more than ten publications) 1. Guest, G.M. et al, Centrifuge method for the determination of the volume of ce in blood, J. Lab. & Clin. Med. 19:757-767, April 1934. 2. Guest.G.M., et al, Hematologic methods in detecting nutritional anemia, in Nutrition: The newer diagnostic methods. 17th ann. conf., Milbank Memorial Fund pp. 138-165, 1938. 3. Guest, G.M. et al, Organic acid-soluble phosphorus compounds of the blood. Physiol. Rev. 21:410-437. July 1941. 4. Guest,G.M., et al, Diabetic coma: metabolic derangements and principles for corrective therapy. Am.J. Med. 7:630-646,1949. 5. Guest, G.M., et al, Urinary excretion of amino-acids during alloxan-induced diabetes in rats, Proc. Soc. Exper. Biol. & Med. 71:410-412. 1949. 6. Guest, G.M. Diabetic coma, Am.J. Med. 7:630, 1949. 7. Guest, G.M. et al, Galactosemia, or galactose diabetes, Diabetes 3:330, Jul. 8. Guest,G.M., et al, Apparatus for continuous recording of insensible weight loss (IWL); clinical applications, Federation Proceedings March 1957. vol 16, 189 Subject: Application for Research Contract File No. TO: US Army Med Research and Development Command Attn: Lt. Col A.D. Sullivan FROM:Director, Division of Nuclear Medicine and Chemistry DATE:7 Nov 58 Dr. Saenger's proposal has been reviewed and the following comments appear pertinent: 1. I have very little hope that a study of amino acid excretions will result in practical data. As is pointed out in the proposal, a number of people have looked at the problem and the levels vary widely and there appears to be no consistency. A great deal of work has been done in animals, again without consistent findings. Apparently the biological variations are so great that one cannot isolate any particular amino acid. The Y-l2 experiment, however, was pretty good. Any study of this nature must also consist of metabolic evaluations including specific food intakes, etc. The proposal does not indicate that this is planned. 2. In spite of the above, I feel that Dr. Saenger should be supported with a high priority. There are so few radiologists in the country willing to do total body radiation that those that are should be encouraged more. His past research experience has been good and I feel that he is a very reliable investigator. If he is supported I am sure he will soon decide that some other phase of the radiation program should be investigated and switch to this. His budget appears somewhat excessive in personnel particularly for the first year. I doubt that he will have enough patients to keep this many people busy. This is certainly true of the statistician. The remainder of the budget appears reasonable. James B. Hartgering, Lt Col MC Director 1 Incl n/c 12 November 1958 MEMORANDUM FOR: COLONEL HULLINGHORST SUBJECT: Application for Research Contract: "Metabolic Changesin Humans Following Total Body Radiation," submitted by Eugene L. Saenger, MD, College of Medicine at University of Cincinnati. 1. This proposal has received favorable comment from Colonel Maupin, Colonel Isherwood, Colonel Hartgering and Colonel Cox. In the opinion of the undersigned, it will augment work being done by Dr. Collins of Baylor and the Sloan-Kettering Institute who are working with humans. Since this proposal will deal with Amino-aciduria or studying urine samples of irradiated patients, it may lead to a possible biological dosimeter. 2. In that most people regard urinalysis as a commonplace thing in a physical examination, it would lend itself easily to field testing as compared to some of the more exotic tests for bio-effects of radiation. 3. Recommend AMS support this contract at a cost of $21,775.00 per annum. Arthur D. Sullivan Lt Colonel, MSC Asst Chief, Biophysics & Astronautics Research Branch 1 Incl Application as Above w/Comments US ARMY MEDICAL RESEARCH AND DEVELOPMENT COMMAND 3 NOVEMBER 1958 MEMORANDUM FOR:COLONEL SULLIVAN SUBJECT: Application for Research Contract, "Metabolic Changesin Humans Following Total Body Radiation", submitted by Eugene L. Saenger, MD, College of Medicine at University of Cincinnati. 1. I have reviewed the subject proposal in detail and think that it will provide us with much needed information on the little-known metabolic changes in humans following irradiation. 2. I know nothing about the responsible or principal investigators, but presume that they must be of high caliber. The University of Cincinnati College of Medicine and associated hospitals are well recognized and accepted in the medical community. 3. This program also fits in well with work being done at the US Army Medical Laboratory, Fort Knox, Ky. 4. I recommend that the AMS support this contract. William W. Cox, Lt Col, MD Chief, Medical Research Branch 1 Incl OFFICE MEMORANDUM UNITED STATES GOVERNMENT TO: Deputy Commander, US Army Medical Research and Development Command FROM: Special Assistant for Research Contract DATE: 24 October 1958 Col Maupin/65957 SUBJECT: Application for Research Contract 1. This investigator is bell known to the undersigned as a competent, honest researcher who will surely perform the research in commendable fashion. Accordingly this proposal should be supported if: a. U. S. Army Medical Research and Development Command supports basic research. b. monies are available. 2. If this proposal can be construed as a means of detection of exposure to radioactivity (and consequently its management),it could be supported as applied research. 1 Incl Clinton S. Maupin Colonel, M. C. OFFICE MEMORANDUM UNITED STATES GOVERNMENT TO: Chief, Radiological Service 20 October 1958 Walter Reed Army Medical Center FROM: Asst Chief, Biophysics and Astronautics Research Branch, U. S. Army Medical Research and Development Command SUBJECT: Application for Research Contract 1. The inclosed copy of research proposal entitled, "Metabolic Changes in Humans following Total Body Radiation," has been submitted for our consideration by Dr. Eugene L. Saenger of the University of Cincinnati, College of Medicine, Cincinnati, Ohio. 2. Request review of the attached proposal and please give your recommendation as to whether or not this study should be supported by the Army Medical Service. 1 Incl Arthur D. Sullivan OTSG Form 108 Lt Colonel, MSC MEDDR TO: Asst Ch, Biophysics & Astronautics Research Branch, US Army Medical Research & Development Command FROM: Chief,Radiological Svc. WRAH Col Isherwood DATE: 22 Oct 1. Recommend approval. 2. Much work has been done on the effects of total body irradiation in and There has been no real effort to date for similar studies on humans. The validity of the assumption that animal reaction is identical with that in humans is pure assumption. There is definite need for basic work in this field. Any correlation of tumor or response to total dose of irradiation by such means as proposed in this project would be of great value in the field of cancer. In addition if by so means such as those proposed accurate knowledge of the total dose of radiation received could be determined it would be of inestimable value in case of atomic disaster or nuclear warfare. The applicant, Dr. Saenger, is well qualified to conduct such research. He is not only an enthusiastic and tireless worker but has the ability to stimulate his coworkers and assistants. He has an unusual analytical mind and is an excellent organizer and administrator. I believe the facilities which he has available are well adapted to the project. It is believed that any funds spent on such a project are well worthwhile. 1 Incl John A. Isherwood n/c Colonel, MC Chief, Radiological Service UNCLASSIFIED File No. DASAMD 920 SUBJECT: NEGOTIATION OF CONTRACT TO: DIRECTOR OF LOGISTICS ATTN: Chief, Contract Management Branch FROM: Deputy Chief of Staff Weapons, Effects and Tests LCDR Garrison/bdj/77615 DATE: 29 October 1959 1. Reference is made to Research Proposal entitled: "Metabolic Changes in Humans Following Total Body Radiation," submitted by the University of Cincinnati College of Medicine on 25 September 1958 to the Surgeon General, Department of the Army. 2. It is requested that Headquarters, Defense Atomic Support Agency, negotiate a contract with the College of Medicine, University of Cincinnati to make a study as described in the Cincinnati proposal with an additional requirement that the supervisor should visit Dr. James Nixon, New York Memorial Center, New York, early in the period covered by the contract to coordinate the work undertaken under this proposal with the work in progress there. Similar work is being carried out at the Baylor University. The diversification is required to achieve adequate results in a field of whole body radiations in humans. 3. The scope of work and procedure are described in the proposal which is attached. The duration of the contract should cover a twelve month time period beginning on or before 15 November 1959. 4. The estimated cost of the contract is $25,085.00 and is acceptable to this division. 5. Accordingly, this memorandum may be considered authority to the Comptroller to make an allotment for Research Proposal, "Metabolic Changes in Humans Following Total Body Radiation," University of Cincinnati, in the amount of $25,085.00 properly chargeable to the Medical Division. Sufficient uncommitted funds are currently available to cover the cost of this contract in program 1-10-52, Investigations of the Effects of Radiation in Humans, Subtask I, Whole Body Radiation. 6. Citation of funds in the amount of $25,085.00 should be made by the Comptroller to the Contract Management Branch, Logistics Division. 1 Incl DAVID LAMBERT Application for Contract Captain USN w/comments Deputy Chief of Staff Weapons Effects and Tests University of Cincinnati College of Medicine Mailing Address Radio-Isotope Laboratory Cincinnati General Hospital Cincinnati 29, Ohio December 4, 1958 Lt. Col. Arthur D. Sullivan Biophysics Research Branch Research and Development Division Department of the Army Office of the Surgeon General Washington 25. D.C Dear Col. Sullivan: I am writing to you concerning some further developments in relation to the research contract which we submitted several months ago. In an effort to investigate possible biological tests as completely as possible with the available clinical materials we have conducted some preliminary conferences with Dr. Herbert Stockinger and Dr. John Mountain of the Occupational Health Field Branch of the U.S. Public Health Service located in Cincinnati. As a result of our preliminary meetings we have decided to study the problem of sulfhydryl radicals in fingernail clippings, a field in which Dr. Stocking's group has done pioneer work. In addition, we are jointly investigating the possibility of studying SH groups in blood. We are also going to study the ultra violet absorption spectra sera in these individuals before and after irradiation. These studies would be carried out in conjunction with the studies proposed in our contract at no additional expense to the program. it is my opinion that these further efforts will make the program of considerably greater value. The research contract which we request will be of the utmost importance in the total work-up and evaluation of the patients under study. I hope that this additional information will be of help, to your professional staff in evaluating the proposed contract. Sincerely. ELS:rvl Eugene L. Saenger. M.D. US ARMY MEDICAL RESEARCH AND DEVELOPMENT COMMAND MEDDH-MR 3 NOVEMBER 1958 MEMORANDUM FOR:COLONEL SULLIVAN SUBJECT: Application for Research Contract, "Metabolic Changes in Humans Following Total Body Radiation", submitted by Eugene L. Saenger, MD, College of Medicine at University of Cincinnati. 1. I have reviewed the subject proposal in detail and think that it will provide us with much needed information on the little-known metabolic changes in humans following irradiation. 2. I know nothing about the responsible or principal investigators, but presume that they must be of high caliber. The University of Cincinnati College of Medicine and associated hospitals are well recognized and accepted in the medical community. 3. This program also fits in well with work being done at the US Army Medical Laboratory, Fort Knox, Ky. 4. I recommend that the AMS support this contract. William W. Cox, Lt Col, MD Chief, Medical Research Branch 1 Incl OFFICE MEMORANDUM UNITED STATES GOVERNMENT MEDDH-SP TO: Chief, Radiological Service 20 October 1958 Walter Reed Army Medical Center FROM: Asst Chief, Biophysics and Astronautics Research Branch, U. S. Army Medical Research and Development Command SUBJECT: Application for Research Contract 1. The inclosed copy of research proposal entitled, "Metabolic Changes in Humans following Total Body Radiation," has been submitted for our consideration by Dr. Eugene L. Saenger of the University of Cincinnati, College of Medicine, Cincinnati, Ohio. 2. Request review of the attached proposal and please give your recommendation as to whether or not this study should be supported by the Army Medical Service. 1 Incl Arthur D. Sullivan OTSG Form 108 Lt Colonel, MSC TO: Asst Ch, Biophysics & Astronautics Research Branch, US Army Medical Research & Development Command FROM: Chief,Radiological Svc. WRAH Col Isherwood DATE: 22 Oct 1. Recommend approval. 2. Much work has been done on the effects of total body irradiation in and there has been no real effort to date for similar studies on humans. The validity of the assumption that animal reaction is identical with that in humans is pure assumption. There is definite need for basic work in this field. Any correlation of tumor or response to total dose of irradiation by such means as proposed in this project would be of great value in the field of cancer. In addition if by so means such as those proposed accurate knowledge of the total dose of radiation received could be determined it would be of inestimable value in case of atomic disaster or nuclear warfare. The applicant, Dr. Saenger, is well qualified to conduct such research. He is not only an enthusiastic and tireless worker but has the ability to stimulate his coworkers and assistants. He has an unusual analytical mind and is an excellent organizer and administrator. I believe the facilities which he has available are well adapted to the project. It is believed that any funds spent on such a project are well worthwhile. 1 Incl John A. Isherwood n/c Colonel, MC Chief, Radiological Service UNIVERSITY OF CINCINNATI COLLEGE OF MEDICINE Mailing Address Radioisotope Laboratory Cincinnati General Hospital Cincinnati 29, Ohio May 8, 1961 Project No. GB