DOCUMENT H Unique Document # January 29, 1947 Major B. M. Brundage Medical Division P. O. Box E Oak Ridge, Tenn. Dear Major Brundage: Transmitted herewith copy No. 19 of the report of the 23-24 January 1947 Meeting of the Interim Medical Committee of the United States Atomic Energy Commission for your information and files. STAFFORD L. WARREN Chairman Interim Medical Committee U. S. Atomic Energy Commission Report of the 23-24 January 1947 Meeting of the INTERIM MEDICAL COMMITTEE U. S. ATOMIC ENERGY COMMISSION by Stafford L. Warren, M.D. Chairman, Interim Medical Advisory Board Members Attending: Dr. R. S. Stone Dr. J. G. Hamilton Dr. G. Failla Dr. A. Hollendaer Dr. John Wirth Dr. S. T. Cantril Dr. H. L. Friedell Dr. J. Svirbely Dr. R. B. Sirkle Dr. L. Donaldson Dr. J. Sterner Dr. James Nolan Dr. A. H. Dowdy Dr. R. L. Vosburgh Dr. A. M. Brues Dr. R. S. Wolf Dr. Louis Hempelmann Dr. K. Z. Morgan Report of the 23-24 January 1947 Meeting of the Interim Medical Committee of the United States Atomic Energy Commission 1. Review and Scope of the Medical Research Program A. Since the inception of the Atomic Bomb Project, an expanding research program aimed at the diagnosis and control of hazards [illegible] to the development of atomic energy has been in effect. These hazards include those injurious effects produced through [illegible] external body exposure to radiations omitted by various radioactive materials during the experimental or processing operations, as well as the chemical toxicity or localized radiation from such materials deposited within the body. Considerable preliminary or pilot experimental and clinical information has been obtained by this research program during the last three years. Of necessity, many fields were completely neglected. The injurious effects following single exposures to large amounts of radiation have been determined experimentally; some of the changes following prolonged chronic radiation exposure have been surveyed; the biological effects which follow the introduction of various toxic and radioactive materials into the body have been partially demonstrated. Such pilot studies have been useful in the estimation of maximum allowable exposure levels of radiation or toxic materials to which personnel can be safely exposed for a period of time, and the control of such hazards by the prevention of such exposures. Such standards were designed for war time expediency and are not necessarily applicable to peace time. While the above information has been extremely useful in this work, it immediately becomes obvious that many critical problems of far reaching scope remain to be solved. Information concerning the method of production of these injurious effects in body tissues is almost completely lacking. No methods are available which might stop or delay the development of radiation injuries. No therapeutic measures are at hand to use following accidental injury due to radiation or radioactive materials. Such problems relate to the fundamental nature of living matter and demand the careful and continued attention of competently trained scientists. B. The following list indicates briefly the survey of the general studies on radiation effects. The known radiations encountered in nuclear fission, as well as those encountered from naturally radioactive substances divide themselves into the following types: alpha rays, beta rays, gamma rays and neutrons. The literature on the biological effects of x-rays and gamma rays is voluminous and a good deal of background information was obtained form this source. On the other hand, very little had been written about the biological effects of alpha rays, beta rays and neutrons. It became necessary therefore, to initiate studies to cope with the unique and pressing problems as rapidly as possible The report of the Medical Advisory Committee to the Director of the Medical Division of Manhattan Engineer District of September 9, 1946 contained the following summary of the problems and the methods of approach being used up to the present. 1. The Physical Measurement of Radiation of Various Types. Here it was and still is necessary to develop better methods of accurately measuring and standardizing the dosage of radiation in two vitally important areas (1) the measurement of the extent of any radiation which might be found in an industrial area and (2) in the biological experimentation. 2. The Biologic Effects of Radiation. Because of the known deleterious effect of radiation on the animal organism, it becomes necessary to determine the effect of controlled dosages of the various types of radiation on various animal and plant species, including marine life. Such observations can be used in the control of possible human exposure and have practical use in medico-legal problems arising from contamination by effluents. Some of the types of biological effects it is possible to study are given below. Only pilot studies have been done on must of these effects. a. The survival time or percentage reduction in normal life span of different animal and plant species following a given dose. b. The genetic effects of radiation as manifested in the development of abnormal individuals from changes in the heredity mechanism. c. Histopathological changes a d demonstrated by abnormal changes in the makeup of the various body tissues. d. Physiological changes produced by the alteration of the normal functioning of living tissues following irradiation. e. Biochemical and enzymatic disturbances which are the potential sources of those physiological abnormalities. 3. Methods for the Detection of Minimal Radiation Damage are being developed directly from experiments of the above types and are applied to the study of the human individual. These include studies on: a. Biochemical and enzymatic changes which may be detected and which, if measurable, can be corrected before irreversible damage has taken place. Examples of such changes would be effects on the metabolism of corpoperphyrins, excretion of abnormal substances in the urine, and the like. b. It has been known that radiation depresses the function of the hematopoietic system (bone marrow, lymph nodes, etc.) and detailed study is indicated to detect early changes under controlled dose radiation with all blood elements under continuous observation. -2- c. The production of anatomical changes such as [illegible] in the integrity of the skin and the like, must likewise be studied under centrified dosage. 4. Methods for the Prevention of Radiation Injuries. These include: a. Methods of physical detection of external radiation by the development of sensitive direct reading instruments capable of the detection of amounts of radiation well below those necessary for demonstrable injury to the animal or human subjects. b. Methods for the determination of harmful amounts of radioactive dusts and gases in air, in water and in body tissues. Many radioactive materials are deposited in the body, like radium, and in such locations product injury to tissue, particularly the bone marrow. Methods based on the determination of dangerous amounts of these substances by examination of the excretion and direct measurements of the body itself are first developed in animals and then applied to human beings. 5. Protective Measures. Studies on(1) the efficiency of shielding against radioactive materials (2) the efficiency of exhaust and ventilating systems against dangerous amounts of dusts (3) the development of protective clothing and [illegible]and (4) the development of remote control processing methods have been extremely important in the Manhattan District protection program to date and will continue to be fundamental to the development of a safe atomic power program. 6. The possible treatment of radiation injury deserves extensive study with high priority. Experimental replacement of the damaged hematopoietic elements destroyed by severe radiation exposure offers one possibility. Detection and neutralization of hypothetical but unknown toxic substances produced by radiation is another possibility. This difficult and fundamental problem deserves consistent and detailed study. All the above studies are of necessity done with alpha, beta and gamma rays and neutrons of varying intensity, singly and in various combinations. Also, the effects of acute and chronic exposure must be determined separately because of their dissimilarity. C. The following list indicates briefly the study of the hazards due to special materials. For brevity, it is preferable to discuss the potential toxicity of special materials by first indicating the types of studies to be carried out, and then listing those materials on which studies have been made or on which studies are necessary. 1. First, an actual determination of the toxicity of a substance must be made, measuring how poisonous it is, both in acute and in chronic exposures. The amounts administered are decreased until asymptomatic levels are found. In this way, toxic levels may be avoided in laboratory and plant environments. Some pilot work in this direction has been completed for a few compounds of uranium plutonium and certain special oils. -3- a. [illegible] and excretion from the body must be studied in chorine experiments at various levels of exposure. b. a careful analysis must be made as to the character of the biological changing specifically, production of physiological, histopathological and biochemical and genetic evidences of damage. Some progress has been made here. c. The nature of those injuries and the mechanism by which they occur must likewise be studied. This affords information as to the necessary protective measures, and indicated therapy after exposure. Very little has been attempted here except in one or tow instances. 2. Preventative measures require study. a. The comparative effectiveness of physical methods for the removal of hazardous dusts; namely, the reduction in skin contact and prevention of ingestion, must be measured. Methods for accurate estimation of such hazards must be developed and used. The efficiency of certain protective chemicals, ointments, etc., must be studied. Only pilot studies have been done here. b. Protective devices such as portable respirators and clothing must be tested for those hazardous substances against which they will be used. No practical mask, military or otherwise, which will protect against some of the worst hazards has been found yet. c. Finally, appropriate investigation must be made of those therapeutic measures to be used in the treatment of both acute and chronic toxicity states. 3. Completion of the various phases of the program outlined above would provide complete information as to those medical aspects which must be taken into account in the protection of the worker, as well as treatment of injury should it occur. The following is a nearly complete list of the substances on which studies of this type are necessary: a. Uranium and its compounds. (1) Uranium metal and its chemical compounds: oxides, nitrate, chlorides, bromide, tetra and hexaflouride, sodium and ammonium diurantes. Some pilot studies have been completed. (2) Uranium chain of heavy metals: Uranium X1 Uranium X2 Radium Polonium Relatively little has been accomplished here. -4- (3) [illegible] (4) [illegible] [illegible] D. Production Hazards. The results of the laboratory studies made on the materials described above are applied to the prevention and control of industrial hazards which arise in the large manufacturing areas where these materials are used in large amounts. These are illustrated by the following: 1. In the Electromagnetic and Diffusion Methods for the isolation of uranium 235, the major hazards are from the uranium compounds, the concentration of uranium X1 and X2, and the special accessory materials and by-products formed in the process of manufacture. 2. In the graphite pile where plutonium (239) is produced on a large scale, the hazards are from the alpha, beta and gamma rays, neutrons, the plutonium metal and its compounds, the various radioactive fission products resulting from the pile operation. 3. The chemical isolation of polonium following its formation in the pile incorporates hazards from alpha radiation following absorption into the body. 4. Chemical purification process in making uranium metal results in hazards from alpha, beta and gamma radiation and the chemical toxicity of the uranium of other products used. 5. Study of the medical aspects of plant programs aside from the determination of the effect of radiation and chemical toxicity, include additional information obtained from plant investigations as from: a. Clinical survey of all exposed personnel. b. Monitoring of hazards by special instruments and methods. -5- [entire top of page illegible] a. B. 1. a. b. c. 2. Delayed Methods. a. Radioactive Devices. Study of methods of protection against the radioactivity deposited at the time of blast. b. Decontamination. Methods of decontamination of soil and the like must be worked out for cleaning up active areas. Some experience is available on this from New mexico and the ships from Bikini which is applicable. c. Investigative equipment. Special equipment must be developed and tested for use in investigating bombed areas. d. Study of casualty effects. Field study of fission clouds, possible injury to water supply, soil and the like, human damage by population surveys. e. Study of treatment of all immediate effects mush as radiation, host and blast. F. Preparation of pertinent information in proper form for use by catastrophe units in production areas. II. Current Medical Research Program. A. To permit continuity, it is recommended the current program be continued during 1947-1948. The current program is reviewed by topics under the following list of the participating organizations: Argonne National Laboratory University of Rochester University of California at Berkeley -6- Columbia University University of Washington [illegible] Chemical Co. [illegible] [illegible] Western Reserve University University of California at Los Angeles University of Tennessee University of Virginia Brookhaven and other future laboratories are not included: B. Future expansion of the medical and biological research program on a long term contract basis (5 years or more) is necessary in order to secure information of a more fundamental character which is necessary in order to cope with the special hazards of atomic energy development. Also it is imperative to open new fields of application for the products of atomic energy in biology and medicine. The Committee feels that such expansion can best be planned and put into effect after the establishment of a Medical- Biological Division. (See Appendix A). After the Regional Laboratories are well organized, the obvious usefulness of isotopes in a wide application to biological research will offer so many tremendous opportunities that developments in this field are assured. C. Specific Projects: (in brief, topical outline) 1. Argonne National Laboratory - Dr. Austin M. Brues, Director. a. The physiological picture of animals exposed to acute and chronic irradiation. b. The effects of irradiation on the structure and functions of the blood and on the hemological defenses against infection. c. The acute toxic effects of external radiation and absorbed radioactive substances: their mechanism of injury; prevention of possible damage and treatment of already injured individuals. d. The abnormal responses of blood cells, cultured tissue cells and single celled organisms to various types of radiation. e. The chronic effects of radiation and radioactive materials in animals. f. The mode of action of radiation in the production of cancer. g. The response to different types of radiation of the various organs and tissues, including tumors. h. Studies on the chemical effects or radiation which are fundamental to its biological response. -7- i. The absorption [illegible] and elimination of radioactive [illegible] from the body. j. The design and standardization of instruments to carry out the foregoing. 2. University of Rochester - Dr. Andrew E. Dowdy, Director. a. Radiation and Radiology Section: (1) Instrument design, measurement standardization, industrial monitoring. (2) Biological effect of tracer amounts of polonium, radium and uranium in human and animal subjects. Application of tracer experiments to serve other parts of the project. (3) Physiological effects of exposure to acute and chronic radiation including the radio-isotopes; search for therapeutic methods of value. (4) Development of possible chemical techniques or methods of detection of radiation damage, and the mechanism by which such effects are produced. (5) By means of spectroscopic methods, to study the distribution of uranium and other heavy metals of importance in animal tissue; a search for possible clues as to the method of bony deposition of radioactive materials. (6) Study of the time intensity factor in radiation, and development of methods of producing instantaneous exposure to radiation (A bomb effect). (7) Study of the metabolism of plutonium polonium, radium, etc., in human subjects. b. Pharmacology: (1) Study of the inhalation toxicity of various uranium, beryllium and thorium compounds. Studies in the mechanism of production of inhalation toxicity. (2) By chemical techniques, studies of the mechanism of uranium fixation in bones, uranium complex formation, methods of excretion of uranium. (3) Acute toxicity effects of uranium, beryllium and thorium compounds by ingestion. (4) Pathological effects of uranium, beryllium and thorium poisoning, and mechanism by which produced. -8- (5) [illegible] and thorium poisoning. (6) Special toxicity studies. (7) Certification of respiratory protective devices. c. Experimental Surgery. (1) Clinical, hematological and pathological effects of acute lethal radiation. (2) Methods of bone marrow transplantation. (3) Studies in bone marrow reserve and radiation effect. (4) Tissue culture studies related to bone marrow production. (5) Effect of folic acid and rutin on marrow regeneration. (6) Studies of metabolism of iodine by thyroid. d. Experimental Hematology. (1) Comparative study of blood histamine after radiation and hematological effects in cells. (2) Studies of life cycle of blood platelets. (3) Studies on life cycle of leukocytes. (4) Studies on marrow reserves after radiation. (5) Evaluation of coagulation defects following irradiation. (6) Techniques for early detection of hematological changes resulting from ionizing radiation. e. Genetics. (1) Continuation of studies of effect of chronic radiation on mice. (2) Continuation of studies on effect of acute and chronic radiation (x-ray) on Drosophila. (3) Histogenetic. -9- f. Training personnel in all above sections. 3. University of California at Berkeley. (1) Metabolism of fission products, medium, [illegible]. (2) Metabolism of possibly hazardous artificially induced radioactive elements from plant construction materials such as chromium, nickel, etc. (3) Metabolism of beryllium. (4) Development of methods of treatment of poisoning from [illegible] elements, notably plutonium and uranium 233 and from the long lived fission products. (5) Behavior of fission products and fissionable elements in soils and plants. (6) Study of alpha particle irradiation and the thyroid gland in animals and man by Asticine (Element 85). (7) Development of methods for decontamination of radioactive ships from Operation Crossroads. (8) The execution of certain radio chemical analyses for Operation Crossroads and training of Army and Navy personnel. (9) A study of the metabolism of elements chemically similar to the fissionable elements and the fission products. b. Dr. John H. Lawrence's program. (1) Biological effects of fission products. (2) A search for uranium compounds that will localize in organs other than the liver and spleen. (3) Biological effects of the disintegration products of boron and lithium following neutron irradiation. (4) Genetics of the carcinogenic effect of beta rays. (5) Physiological chemistry of the biological action of radiations. (6) Changes in water balance following radiation injury. -10- (7) [illegible] (8) [illegible] c. Dr. Robert S. Stone's program. (1) Studies in whole [illegible] radiation of human subjects by external and internal radiation. (2) Studies on the materialism of radioactive iodine in animals and man. (3) Joint studies with Dr. Joseph G. Hamilton to evaluate the therapeutic applications of the fission products and the fissionable elements. (4) Exploration and therapeutic applications of other radioactive elements and compounds. 4. Columbia University - Dr. G. Failla, Director. a. Measurement of fast neutrons for biological purposes. b. Measurement of time dose relationship resulting from radioactive isotopes distributed in the tissues. c. Measurement of specific gamma ray emission. d. Study of the quantitative relationships in chemical effects produced by gamma rays and fast neutrons. e. Further study of eye and gonad injury produced by fast neutrons. f. Study of the biological action of ionizing radiations. g. An attempt to reduce radiation injury. h. Study of the distribution of radioactive isotopes in tissues and cells. i. Protection data for the safe handling of radioactive isotopes in small amounts. j. Training of personnel. k. Measurement of very high energy radiations for biological dosage. 5. University of Washington School of Fisheries - Dr. Lauren R. Donaldson, Director. a. The work of this project is to explore the general problem of the effect of radiation on aquatic organisms, and in particular, to study the problems arising from the discharge effluent from the Hanford plants into -11- [illegible] (1) Acute and chronic effects of [illegible] radiation on fishes. (2) Breathing studies on [illegible] following irradiation. (3) Studies of the effects of the Hanford effluent on salmon and trout. (4) Effects of internally deposited radioactive materials on aquatic organisms. (5) Field studies on the effect of possible Hanford pollution on aquatic life in the Columbia River. (6) Studies on the transfer of radioactive materials in "food chains", starting with the simpler biological forms (i.e. plankton) and following the distribution and fate of such materials as these contaminated animalcules are successively eaten and metabolized by higher forms (fishes, etc.) (7) Feeding experiments using radioactive materials in the foods. 6. Hanford Engineer Works (Research Project) - Dr.Simeon T. Cantril, Director. a. Health physics research and development in radiation monitoring, instrumentation. b. Training of technicians and other personnel in problems of radiation protection. c. Applied biologic research relative to phases of radiation hazard peculiar to Hanford Engineer Works operations and waste disposal: (1) Soil, water and air contamination by radioactive materials. (2) Studies under controlled conditions of the effects of radioactive materials on domestic animals. (3) Studies under controlled conditions of the effects of radioactive materials on vegetation. (4) Fish Studies: (In collaboration with University of Washington, project listed previously.) (a) Effects of waste effluent on salmon and trout. (b) Effects of internally deposited radioactive materials. -12- (c) [illegible] (d) [illegible] 7. [illegible] a. Studies of the biological effects of [illegible] fast neutrons, beta and gamma radiation are in progress as a follow-up of previously reported. b. Effects of plutonium on bone healing is being studied. c. The [illegible] used to study the indirect effects of radiation. d. A concentrated attack is being made on radiation effects or the rate of [illegible] and the general genetical makeup of the cell, including cytoplasmic factors. e. Tracer experiments of a number of metabolic systems have been initiated using various micro-organisms. f. Effects of radiation on cell [illegible] nucleic [illegible] are being studied by modern physical- chemical tools, (including isotopes.) g. Radiation effects are being investigated on blood constituents and blood forming organs as well as on the nervous system. h. Cooperative research arrangements are being made with the Universities of tennessee, Vanderbilt University, Washington University, University of Pennsylvania, John Hopkins University and Carnegie Institution. i. Close cooperation with the National Institute of Health and the National Cancer Institute has been set up. j. Instrumentation of radiation monitoring developed by health physics will be continued. k. Health physics research is to be extended. l. A training program. 8. [illegible] Chemical Co. (Dayton) - Dr. James Svirbely, Director. -13- [illegible] [a. through h. illegible] 9. Western Reserve University - Dr. [illegible] L. Friedell, Director. a. Studies on toxicity of [illegible] (1) Biological effects. (a) Study of biological effects of [illegible] lethal effects, weight changes, histopathologic, hematologic and biochemical changes. (b) Study of biological effects of insoluble thorium compounds as in a(1) above, but also includes radiation effects. (2) Distribution studies. (a) Study of thorium distribution in tissues by chemical assay. (b) Study of distribution by tracer technique. -14- [entire top of page illegible] b. Study of radiation effects of internally distributed radioactive elements. (1) "Summation" studies of several radioactive elements of widely varying specific immunization. c. Synthesis of compounds into which radioactive elements may be introduced. (1) Comparison of radiation effects of various beta emitters alternately introduced into the same compound. (2) Comparison of radiation effects of beta and alpha emitters (wide divergence of specific ionization) alternately and concomitantly introduced into the body. d. Study of the distribution of the above noted radioactive compounds. (1) By assay of radioactivity in tissues. (2) By radiosutographs of tissues and similar suitable means. 10. Los Alamos - Dr. Louis Hempelmann, Director. a. Plant hazard research. (1) Development of method for the determination of minute amounts of plutonium in the [illegible] and body tissues of humans and animals. (2) Determination of the fraction of injected plutonium excreted per day by humans and animals. (In collaboration with the University of Rochester). -15- (3) [illegible] (4) [illegible] (5) [illegible] (6) Development of safe techniques for plant operation. (7) Clinical studies on [illegible] b. Proposed fundamental and applied research program. (1) The fundamental studies on the [illegible] effects of radiation. (2) Treatment of acute radiation disease. (3) Methods of detecting early radiation injury. (4) Continued studies of the metabolism of plutonium, U-235 and other radioactive materials. (5) Detection of accumulated plutonium in the lungs. (6) Biochemical studies of nucleoprotein and the effect of radioaction of the fundamental physiology of the cell. (In collaboration with Washington University, St. Louis, Mo.). (7) Detailed study of absorption of plutonium from contaminated surfaces and wounds. (8) Any special problems arising from new operating hazards on this project. 11. University of California at Los Angeles - Dr. Stafford L. Warren, Director. a. The mechanism of blood vessel injury by radiation. b. Bone marrow injury by radiation, its repair and treatment. c. Mechanism of "metal" deposition in bone and mechanism of removal from bone. d. Protein degradation following radiation and chemical injury. 12. Contracts approved by the Interim Medical Committee and awaiting U. S. Atomic Energy Commission approval: -16- a. University of Washington - Dr. Chanutin, Director (1) Study of the effects of various types of radiation (alpha, beta, gamma and neutrons) on the circulating blood proteins by electrophoresis and protein fractionization technique. To determine whether means of early detection of radiation design can be accomplished in this way. b. University of Tennessee - Dr. Henry Wills, Director. (1) Study of the mechanism of toxic affects of uranium and other heavy metal compounds on the kidney. This is a continuation of Dr.Wills' work with the Rochester Manhattan Project during the war and contributes to that general study. D. Estimated total Health-Safety research budget for fiscal year 1946-1957 and 1947-1948. 1. Fiscal Year Fiscal Year Probable Contractor 1946-1847 1947-1948 Local Budget Los Alamos $ 100,000. $ 200,000. $ 500,000. Univ of Rochester 1,200,000. 1,300,000. 1,800,000. UofC at Berkeley Program II 3a 100,000. 125,000.) II 3b 115,000. 200,000.):- 400,000. II 3c 20,000. 35,000. Clinton Lab 180,000. 500,000. 500,000. Monsanto (Dayton) 40,000. 225,000. 200,000. Hanford 200,000. 500,000. 500,000. Western Reserve 100,000. 155,000. 200,000. U of Washington 28,000. 100,000. 150,000. Columbia University 100,000. 100,000. 100,000. Argonne 1,200,000. 1,400,000. 1,500,000. Brookhaven 400,000. 500,000. U of Virginia 25,000. 50,000. 50,000. U of Tennessee 16,000. 16,000. 16,000. U of C at Los Angeles 100,000. 200,000. 200,000. Western Regional 400,000. 500,000. ------------------------------------------------------------ Total Medical- Biological $3,524,000. $5,906,000. $7,116,000. ------------------------------------------------------------ Health-Physics 500,000. 1,000,000. 1,300,000. Training (?) 50,000. 5,000,000. 1,750,000. Field Survey & Service Research (?)300,000. 2,000,000. 3,000,000. ------------------------------------------------------------ Estimated Grand Total $7,074,000. $13,906,000. $13,166,000. ------------------------------------------------------------ Note: See D2 for estimated totals of Regional Laboratories including budgets for research in the participating universities. Only those currently active are shown. -17- 2. [illegible] Regional Biological Health Field Survey & Laboratory Training Medical Physics Service Research Argonne $ 500,000. $ 4,000,000. $ 250,000. $ 100,000. Brookhaven 500,000 4,000,000. 250,000. 1,425,000. Clinton Lab 250,000. 1,000,000. 250,000. 200,000. Hanford 100,000. 1,000,000. 100,000. 50,000. Los Alamos 200,000. 750,000. 250,000. 25,000. Western 200,000. 1,000,000. 200,000. 100,000. --------------------------------------------------------------- Total $1,750,000. $11,750,000. $1,300,000. 2,000.000. --------------------------------------------------------------- Grand Total $16,800,000. --------------------------------------------------------------- This total should be equivalent to approximately 20-25% of the total research effort of the U. S. Atomic Energy Commission. 3. Example of estimated Medical Research Budget for a Regional Laboratory. 1949-50. Medical- Health- Field Survey Brookhaven Training Biological Physics and Services Local $ 100,000. $1,000.000. $ 50,000. $ 50,000. Rochester 175,000. 900,000. 25,000. 700,000. Columbia 25,000. 200,000. 25,000. 50,000. Cornell 25,000. 200,000. Harvard 50,000. 200,000. 25,000. Yale 25,000. 200,000. M.I.T. 50,000. 200,000. 50,000. 50,000. Princeton 25,000. 50,000. Brown 50,000. * Others 25,000. 1,000,000. 25,000. 500,000. ----------------------------------------------------------------- Total $ 500,000. $4,000,000. $ 200,000. $1,425,000.** ----------------------------------------------------------------- *May be directed into new or above affiliated group as need arises for investigation of certain problems. **This total is large because this area carries the major industrial and production activities. III. Health-Physics. A. Health-Physics is the name applied to a newly developed and highly specialized branch of Radiology. The principal function of Health-Physics has been to make a study of radiation problems and to devise means of preventing radiation damage. The records obtained by this group are of medico-legal importance. The manpower shortage in this field is acute. -18- [illegible] B. [illegible] [illegible] 3. Building surveys. A daily measurement and recording of working areas. 4. [illegible] An approved monitoring of the radiation level of the air [illegible]. The cost of the service section of health-physics should be [illegible]. 5. The problem of the research and development sections of the health physics [illegible] have been quite varied and perhaps can be indicated by the following list which presents a few typical examples: 1. Instrument development a. Personnel monitoring instruments such as pocket meters and film badges have been developed by still need improvement. b. Many problems were encountered in the development and production of fairly suitable portable and fixed meters to measure the alpha, beta, gama, thermal neutron and fast neutron exposures received by personnel under varying situations. c. Survey meters of all types, especially electrostatic and electronic instruments were developed and produced. These need considerable improvement, particularly for alpha and neutron measurements. 2. Special measurement of energies to which personnel is exposed. a. Relative to instruments. -19- (1) [illegible] (2) (3) (4) (5) (6) b. Applied physics measurements. (1) Develop remote control operations for working with radioisotopes. (2) Make a study of various types of shielding, radiation shipping containers, etc. (3) Develop methods of determining the amount of plutonium, polonium, uranium, etc., that are fixed in the body. (4) Develop methods of estimating excessive radiation exposures from the amount of radioactive sodium and potassium in the blood. (5) Measure the efficiency of masks, respirators, gloves, and clothing in preventing body radiation exposure. (6) Develop and operate methods of decontamination. (7) Study new methods of radioactive waste disposal. (8) Help in the design of new buildings to minimize radiation exposure. c. Physics research. (1) Carry out "sky-shine" experiments. (2) Study effects of high energy radiation on tissue. (3) Study radiation scattering in shields and in tissue. (4) Determine value of n/r, etc. -20- d. Theoretical. (1) Make numerous tolerance calculations to determine radiation hazards presented by external and internal exposure. (2) Calculate radiation from extended sources. (3) Set up radiation protection tables, rules, regulations, etc. e. Educational program. (1) Train health physicists for other atomic energy sites, for those universities and laboratories that have radiation problems, as well as for the Army and Navy. (2) Consult with numerous individuals and committee on radiation problems. (3) Help outside organizations to check their laboratories and operations for radiation hazards. (4) Train chemists, physicists, etc, who are not health physicists but who need a proper respect for radiation problems. (5) Operate health-physics training programs. This is urgently needed. None are available now. D. The table in Section II D1 and 2 gives an indication of the present and future total manpower an total expenditures of health-physics. Past annual costs have been quite large but are not available. IV. Training program. A. One of the most serious difficulties impeding the immediate progress of the general program designed to safeguard civilian and industrial personnel against the deleterious effects of the products of nuclear energy and the promotion of the beneficial utilization of such products is the lack of a sufficient number of well-trained personnel. Such a situation has arisen from the combination of a hiatus in basic science training during the war and the uniqueness of the problems confronting the Atomic Energy Commission. It is recommended that an extensive training program be sponsored by the Atomic Energy Commission to facilitate the training of suitable personnel in the various branches of atomic energy. As a result of the crowding of the universities, some building program will probably be necessary. Such a program should embody the following objectives: 1. To increase the usefulness of present project personnel, academic seminars should be instituted and in certain instances, attendance of sources in the basic sciences of physiology, histology, biology, physics, bio- physics, chemistry, etc. should be required as a part of their regular scheduled duties. -21- 2. To [illegible] to present and future programs of the Atomic Energy Commission. Average time one month. 3. To train a backlog of technical professional personnel in the medical, biological, industrial hygiene and health-physics aspects of atomic energy. The objective would be to accept well qualified doctors of philosophy, physicians and techniques for a training period of not less than one year in the special branches of bio-physics, biology, isotope techniques, toxicology, health-physics, related industrial hygiene and the various technical procedures pertaining to the enumerated subjects. In order to provide an additional backlog of trained personnel for the future and to promote cordial public relations, facilities and fellowships should be established to encourage suitable post graduate candidates to elect major subjects for their degrees in those fields pertaining to atomic energy. This aspect of the program envisions a training period of one to four years, depending upon the prior qualifications of the candidate. B. It is recommended that a committee be appointed by the Atomic Energy Commission for the development of an integrated training program for the education of scientific workers in the correlation of atomic energy with the national sciences, biology and medicine. V. Recommendations on Organization. A. Administrative creation of a new division of Health-Safety. 1. The responsibility for the health and safety of personnel employed by the Atomic Energy Commission in the conduct of their program extends throughout the entire program. Many of the hazards are not well understood. Frequently new research findings or new production procedures bring to light entirely new problems with unknown hazards and unpredictable safeguards. 2. Careful health and safety planning is necessary in anticipation of predicted hazards. Such planning must be in step with the plans of the four statutory divisions of the Atomic Energy Commission. Biological experimental work is slow, difficult and time consuming. Anticipatory planning and conduct of large scale biological work is mandatory so that results may be available as soon as possible before any exposure of personnel occurs. Thus a large effort, equivalent to perhaps 20-25% of the total research appropriation should be put into a health-safety program. B. Health-Safety Advisory Board. 1. It is recommended that a Health-Safety Advisory Committee be formed by administrative action consisting of nine members, three to be -22- appointed for two years, three to be appointed for four years and three to be appointed for six years. This Committee should ------the statutory General Advisory Committee to the Atomic Energy Committee and should be appointed by the Atomic Energy Committee to advise it in matters relating to medical, biological, industrial hygiene, health-physics and related research problems. It is further recommended that the Health Safety Advisory Committee recommend the appointment of appropriate advisory sub-committees. 2. The following list of fourteen names is recommend for consideration in making the appointment on the Health-Safety Advisory Board to the Atomic Energy Committee" a. Medical: Dr. Joseph Aub, M.D. - Harvard (Consultant to Manhattan) Dr. Hymer L. Friedell, M.D. - Western Reserve University (Manhattan) Dr. Robert S. Stone, M.D. - University of California at Berkeley (Manhattan) Dr. Stafford L.Warren, M.D. - University of California at Los Angeles (Manhattan) b. Biological: Dr. Austin M. Brues - Argonne Nat'l. Laboratory Dr. Joseph G. Hamilton, M.D. - University of California at Berkeley Dr. M. E. Jacobs, Ph.D. - University of Penn. (non-Manhattan) Dr. Hans Muller, Ph.D. - Indiana University (non-Manhattan) c. Industrial: Dr. Simeon T. Cantril, M.D. - Hanford (Manhattan) Dr. Andrew H. Dowdy, M.D. - University of Rochester (Manhattan) Dr. James Sterner, M.D. - Eastman Kodak Co. (Manhattan) d. Health Physics: Dr. G. Failla, Ph.D. - Columbia University Dr. K. Z. Morgan, Ph.D. - Clinton Laboratory Dr. H. M. Parker, Ph.D. - Hanford Note: In this Committee, there is no representative from Los Alamos (Dr. louis Hempelmann); Brookhaven (unappointed); U.S.P.H.S. (Dr. E. Williams); Army (Colonel James P. Cooney) Navy (Captain George Lyon) nor the small university contractors (no recommendation). C. It is recommended that a Division of Health Safety be created by administrative action and that its responsibilities and authority be on par with the four statutory Divisions of Production, Research, Engineering and Military Applications. -23- The intended [illegible] on the current health safety program is a result of personnel [illegible] and the critical nature of its function and responsibilities has suddenly increased with the reactivation of the Atomic Energy Commission Research Programs. D. It is recommended that the [illegible] of the Division of Health-Safety be appointed as soon as possible and that he hold the degree of Doctor of Medicine and that if possible, he be familiar with some large portion of the Manhattan District medical program in order to stabilize the future of the current program. The following list of suitable candidates have been selected and proposed in the order named by this Committee for consideration as the Director of Health-Safety. These men have had extensive executive experience with the Manhattan Project and are Doctors or Medicine except for Dr. Zirkle who was included in the secret balloting of the Committee, and because of his records, warrants consideration for this post. Name Age Title Background Dowdy, Andrew H. 42 Prof of Research in medicine, Radiology, radiology and U of R chemotherapy; cancer and radioisotopes. Clinical training and teaching in Radiology. Director Rochester Manhattan Project. Cantril, Simeon T. 40 Consultant in Clinical and research Radiology experience in radiology Hanford and cancer. Former Project Former medical director, Hanford Engineer Works. Stone, Robert S. 51 Professor of Clinical and teaching Radiology, experience in radiology U of California research with isotopes and cancer. Director of Health-Safety program, Metallurgical Project, Manhattan Dist. Wirth, John (?)40 Principal Cancer research, Investigator clinical service, National Clinton Laboratories. Institute of Health Baltimore, Md. Hamilton, Joseph 39 Ass't Professor Clinical and teaching of Medicine experience, biological Univ of and medical applications California of nuclear physics; radio-chemist. - 24 - Hemplemann, Louis 57 Medical Research Experience in research Director, Los in biophysics and Alamos Project chemistry and large scale radiological safety at Alamogordo and Bikini Brues, Austin M. 40 Ass't Professor Research in cancer and Medicine Univ. shock and isotopes. of Chicago Clinical and teaching training in Internal Med. Starter, James 42 Director, In- Experimental and Clinical dustrial problems in industrial Eastman Kodak hygiene and toxicology. Co. Instructor in medicine, Medical Director for electromagnetic process at Oak Ridge. Zirkle, Raymond R. 42 Director of Research in experimental experimental biology Biophysics biology, radiology and Institute teaching. Univ of Chicago Wolf, Bernard S. 35 Probable Medical Clinical experience in Director, Brook- radiology and surgery. haven Board of Radiology member. Previously a member of Medical Section, Manhattan. Brundage, Richard M 36 Chief, Medical Clinical training and Division, Man- Industrial Medicine. hattan Dist. Other Doctors of Medicine of high caliber with executive experience who either work or are still associated with the Project, are listed in alphabetical order by the Chairman for consideration. They all have considerable knowledge of the overall program: Dr. John Perry - Whiting, Indiana Dr. Hymer Friedell - Western Reserve Univ., Cleveland Dr. Joe Howland (Maj, AUS) University of Rochester Dr. Leon Jacobson - University of Chicago Dr. Adolph Farmer - Schenley Distributors, N.Y.C. Dr. J. J. Nickson - Argonne National Laboratory Dr. James Wolen - Geo. Washington Univ., St. Louis, Mo. Dr. C. J. Watson - Minneapolis, Minnesota. -25- The following are [illegible] for consideration because of their knowledge of the field of radiation research and cancer, but no knowledge of the project:. Dr. G. P. [illegible], Memorial Hospital, New York City. Dr. Shields Warren, Harvard University Dr. Robert Howell, Stanford University Dr. John L. Lawrence, University of California There are undoubtedly others. E. The [illegible] Committee was unable to finish its consideration of other committees within the two days of conferences. In view of the importance of making decisions promptly so that a working force may start in the near future, the Chairman has taken the option of interpreting the partially [illegible] intent of the Committee and offers the following organization and names for consideration by the Commission, Mr. Wilson and [illegible] Director of Health-Safety as a step-gap for the period until July 1, 1947. More mature consideration, in the meantime, by the Director of Health-Safety and the Medical Advisory Committee can make the proper realignments with the assistance of experienced advice from appropriate subcommittees formed from the membership of such bodies as the National Academy of Science,The Committees on Growth of the National Research Council, the United States Public Health Service, the various foundations and other appropriate agencies. The following list of names is submitted for consideration. it was the intention of th Interim Committee to include as many institutions and as many fields of related endeavor as possible. There is no intention of rating the persons named and no attempt was made to segregate as to specialty or institution. I should also be understood that this list of 100 is by no means a complete coverage of the field but is a working nucleus. Name Location Specialty ---------------------------------------------------------------- Dr. C. R. Rheads Memorial Hosp. (Cornell) Cancer Research Dr. Robert S. Hewell Stanford University Radiology Dr. Frank B. Jewett Press Nat'l Acad. Sc. Physics Dr. Wm. J. Robbins NYC Botanical Gardens Botany Dr. Eugene P. Pendergrass Univ. of PA Radiology Dr. Perrin Long Johns Hopkins Univ. Chemotherapy Dr. Raymond E. Zirkle Univ. of Chicago Radiobiology Dr. Paul Neal Nat'l Inst. Health USPHS Indus. Hygiene Dr. Geo. P. Berry Univ of Rochester Bacteriology Dr. Paul Asbersold Oak Ridge Biophysics Dr. Waldo Cohn Clinton Lab Radiochemistry Dr. H.L. Friedell Western Reserve Radiology Dr. Louis Hempaimann Los Alamos Radiobiology Dr. Wm. F. Pele Univ. of Rochester Biophysics Dr. J.G. Hamilton Univ. of California Radiobiology Dr. Andrew H. Dowdy Univ. of Rochester Radiology Dr. G. Failla Columbia University Biophysics Dr. Paul Hahn Vanderbilt Univ. Physiology Dr. J.C. Aub Harvard Indus. Medicine -26- [majority of organizational table and is illegible] Name Location Specialty Dr. [Illegible] Washington Univ. Dr. [Illegible] Univ. of Chicago Biophysics Dr. R. S. [Illegible] Univ. of California Radiology Dr. [Illegible] Univ. of Chicago Medicine Dr. [Illegible] Columbia Univ. Chemistry Dr. [Illegible] Yale University Botany Dr. [Illegible] Carnegie University Anatomy Dr. [Illegible] Yale University Pathology Dr. [Illegible] Columbia University Biostatistics Dr. [Illegible] Wisconsin Univ. Botany Dr. [Illegible] W.S.P.H.S. Cytology Dr. Sewald Wright Chicago University Zoology Dr. Wright Langhan Los Alamos Biophysics Dr. A. P. Krueger Univ. of California Bacteriology Dr. S. Rose Univ. of Illinois Biochemistry Dr. Lauren Donaldson Univ. of Washington Zoology Dr. L. Carmichael Tufts University Psychology Dr. T. M. Rivers Rockefeller Foundation Virus Research Dr. Hart Stern Univ. of Rochester Genetics Dr. L. H. Snyder Ohio State Univ. Genetics Dr. E. W. Goodpasture Vanderbilt Univ. Pathology Dr. E.N. Harvey Princeton Univ. Physiology Dr. [Illegible] Univ. of Rochester Genetics Dr. V. S. Trinity Stanford University Zoology Dr. E.V. Cowdry Barnard Free Skin & Cancer Hospital Cytology Dr. Francis O. Schmitt MIT Zoology Dr. D.S. Phemister Univ. of Chicago Surgery Dr. F. Fremont-Smith Josiah-Macy Foundation Psychiatry Dr. Harold Hodge Univ. of Rochester Pharmacology Dr. Garhardt Dessauer General Electric Co. Biophysics Dr. Karl Voegtlin Nat'l Institute of Health Toxicology Dr. Wallace O. Penn Univ. of Rochester Pharmacology Dr. Phillip Drinker Harvard University Physiology Dr. Howard Haggard Yale University Industrial Hygiene Dr. Robert A. Kenoe Univ. of Cincinnati Industrial Hygiene Dr. James Sternan Eastman Kodak Co. Industrial Medicine Dr. Donald D. Irish Dow Chemical Co. Industrial Toxicology Dr. Geo H. Whipple Univ. of Rochester Pathology Dr. H.T. Karsaer Western Reserve Pathology Dr. Shields Warren Harvard University Pathology Dr. S. Payne Jones Yale University Bacteriology Dr. Peyton Rous Rockefeller Inst. Cancer Dr. M.C. Winternitz Yale University Pathology Dr. Willard Allen Washington Univ. OBS & Endocrinology Dr. M.B. Visscher Univ. of Minnesota Physiology Dr. E.E.K. Geiling Univ. of Chicago Physiological Chem. Dr. Andrew C. Ivy Northwestern Physiology Dr. L.T. Fairrall USPHS Indus. Toxicology -27- Name Location Specialty Dr. [Illegible] Indu. Medicine Dr. [Illegible] U.S. Bureau of Mines Toxicology Dr. [Illegible] U.S.P.H.S. Toxicology Dr. [Illegible] U.S. Food & Drug Indus. Toxicology Dr. [Illegible] Johns Hopkins Surgery Dr. J.J. Morton Univ. of Rochester Surgery Dr. Conrad Elvehjem Univ. of Wisconsin Physical Chemistry Dr. R. R. Sayers U.S. Bureau of Mines Indus. Toxicology Dr. Alton ---- Tulane University Surgery Dr. J.L. Bollman Mayo Foundation Physiology Dr. H.W. Smith New York University Physiology Dr. A.D. Welch Western Res Univ. Pharmacology Dr. W.D. McWider Univ. of No. Carolina Pathology Dr. S.C. Madden Emory University Pathology Dr. J.S. Lawrence Univ. of Rochester Medicine Dr. V. du Vigneeud Cornell University Biochemistry Dr. Geo. W. Corner Carnegie Institute Anatomy Dr. C.F. Kettering General Motors Corp Research Dr. J.W. Howlend Univ. of Rochester Medicine Dr. Wm. Gohrman Dupont Co. Indus. Medicine Dr. D.D. Van Slyke Rockefeller Inst. Biochemistry Dr. D.A. Maynard Cornell University Biochemistry Dr. Wm. A. Hoyes Univ. of Rochester Chemistry Dr. Joseph ---- Univ. of Cincinnati Indus. Toxicology Dr. H.B. Van Dyke Rutgers University Pharmacology Dr. H.S. Gasmer Rockefeller Inst. Physiology Dr. F.A. Bryan Univ. of Rochester Indus. Medicine Dr. Carl F. Cori Washington Univ. Biochemistry Dr. Charles G. King Nutrition Found Corp Nutrition Dr. H.W. Beams Univ. of Iowa Zoology Dr. Rene DuBos Rockefeller Inst. Bacteriology Dr. Anton Carlson Univ. of Chicago Physiology Dr. George Beadle Calif. Inst. Tech Biology -28- FOR REFERENCE SEE (3bb01) - 29 - APPENDIX A I. Preview and approval of past program (Medical Summary 1945-46 to be reviewed and approved if possible) II. Scope of Research Program 1946-47 (Appendix A) University of Chicago - Argonne Regional Laboratories University of Rochester University of California Hamilton Stone Columbia University University of Washington, Seattle Monsanto Chemical Corp. (Clinton Laboratories) USPHS Monsanto Chemical Corporation (Dayton) Los Alamos - Western Reserve University Contracts Awaiting Approval: University of Virginia University of Tennessee III. Recommendations for Future Research Policy A. Scope of fundamental work (that approved in September meeting) (Appendix A) B. Human Testing with special materials IV. Organization of Medical Responsibilities A. Advisory Committee 1. Advisory Committee on Medical Research and application (Tolerances, Standards and Hazard Interpretations in addition to research programs). 2. Advisory Committee on Industrial Medicine and Toxicology. 3. Advisory Committee on Health Physics. B. Recommendation for the continuation of operation of the Medical Division at the present level with the available reduced force now in that office as well as salary schedule. - 1 - APPENDIX a (Cont'd) [top of page illegible] V. [illegible] VI. Representation on Advisory Board to Atomic Energy Commission VII. Release of Information Recommendation for a made meeting of all present and former Atomic Energy Commission medical research, at which time a program (4 days) would present accurate information on all medical aspects related to atomic energy then available for security clearance. This meeting would be open to scientific personnel in all parts of the country. The following suggestions are pertinent: A. Approximately 6-8 months preparation would be required. B. A central location should be selected to insure a maximum attendance. C. Abstracts of the program should be circulated at least one month prior to the date of the meeting (similar to that procedure used by the Federated Societies of Physiology, Biochemistry, etc.) These abstracts should be approved by a previously selected editorial board before release. D. Consideration should be given toward the founding of a new scientific society whose major interest would be base on problems of radiobiology as related to medical interest. The Journal of Radiobiology now being launched could well be made the official journal of this society. - 2 - APPENDIX A (Cont'd) Types of study include I General Studies in Radiation including (1) physical measurement of radiation, (2) biological effects of radiation,(3) methods of detection of minimal radiation damages and (4) methods for the prevention of radiation injuries. II Records due to special Materials (for non-radioactive, radioactive and fission materials) (1) degree of toxicity (2) preventative measures. III Special Production Hazards and IV Records of Military Uses. Argonne National Laboratories (University of Chicago) 1. General physiological picture of acute and chronic radiation. 2. Radiation effect on blood clotting, lymphocyte distribution and spread of infection. 3. Toxic effects of external radiation and absorbed radioactivity. 4. Response of blood cells to various types of radiation. 5. Chronic effects of radiation and radioactive materials in animals. 6. Mode of action of radiation in carcinogenesis. 7. Chemical and physiological basis of radiation effects. 8. Metabolism of radioactive elements. 9. Instrument standardization, design, etc. University of Rochester Radiation and Radiology Section 1. Instrument design, measurement standardization, industrial monitoring. 2. Biological effect of tracer amounts of polonium, radium and uranium in human and animal subjects. Application of tracer experiments to serve other parts of the project. 3. Physiological effects of exposure to acute and chronic radiations including radio isotopes; search for therapeutic methods of value. 4. Development of possible chemical technique or methods of detection of radiation damage and the mechanism by which such effects are produced. 5. By means of spectroscopic methods to study distribution of uranium and other heavy metals of importance in animal tissue; search for possible clues as to the method of bony deposition of radioactive materials. 6. Study of the time intensity factor in radiation and development of methods of producing instantaneous exposure to radiation (A bomb effect). 7. Study of the metabolism of plutonium polonium, radium, etc., in human subjects. Pharmacology 1. Study of the inhalation toxicity of various uranium, beryllium and thorium compounds. Studies in the mechanism of production of inhalation toxicity. - 3 - APPENDIX A (Cont'd) 2. By chemical technique, studies of the mechanism of uranium ---- in bones, uranium complex function, methods of excretion of uranium. 3. Toxicity of uranium, beryllium and thorium compounds by ingestion. 4. Pathological effects of uranium, beryllium and thorium poisoning and mechanism by which produced. 5. Physiological effects of uranium, beryllium and thorium poisoning. Experimental Surgery 1. Clinical, hematological and pathological effects of acute lethal radiation. 2. Methods of bone marrow transplantation. 3. Studies in bone marrow reserve and radiation effect. 4. Tissue culture studies related to bone marrow production. 5. Effect of folic acid and rutin on marrow regeneration. 6. Studies in metabolism of iodine by thyroid (15%). Experimental Hematology. 1. Comparative study of blood histamine and hematological effects in cells. 2. Studies on life cycle of blood platelets. 3. Studies on life cycle of EBC leukocytes. 4. Studies on marrow reserves after radiation. 5. Evaluation of coagulation defects following irradiation. 6. Techniques for early detection of hematological changes resulting from ionizing radiation. Genetics 1. Continuation of studies of effect of chronic radiation on mice. 2. Continuation of studies on effect of acute and chronic radiation (X-ray) on Drospphilia. 3. Histogemetics. University of California 1. Studies of the metabolism of plutonium, uranium and fission products in rats and men. 2. Fission product tracer studies. 3. Metabolism of radium, actinium, americium and curium in animals and men. 4. Studies (pilot) on possibly hazardous artificially induced radioactive elements, i.e. chromium, nickel, etc. 5. Beryllium tracer studies. 6. Treatment of plutonium poisoning. - 4 - 7. Behavior of fission products in soils. 8. Biological effects of fission recoils. 9. Search for other U compounds which will localize in organs other than liver and spleen (15%). 10. Biological effect of disintegration products of baron and lithium of the neutron irradiation (15%). 11. Study of element 83 in the thyroid (15%). 12. Training of Crossroads personnel. 13. Studies in whole body radiation of human subjects. 14. Studies on metabolism of radioactive iodine in animals and men. Columbia University 1. Studies on the measurement of fast neutrons for biological dosage. 2. Development of a method of measuring neutron dose by chemical means. 3. Measurement of radioactive isotopes for biological and medical application. 4. Correlation of tissue doses and biological effects produced by external irradiation and by radioactive isotopes internally administered. 5. Exploratory biological experiments to extend use of radio-active isotopes as tracers on therapeutics agents (15%). 6. Studies of the fundamental biological action of ionizing radiation. 7. Measurement of the radiation of radioactive isotopes to provide data for the protection of personnel and films in transit. University of Washington (Seattle) 1. Acute and chronic effects of external radiation on fishes. 2. Breeding studies on salmon following radiation. 3. Studies on the effects of hanford effluent on salmon and trout. 4. Effect of internally deposited radioactive materials on fishes. 5. Field studies on the effect of possible Hanford pollution on fish life of the Columbia River. 6. Plankton experiments - effect of radiation on higher forms (new). 7. Feeding experiment on deposited radioactive materials (new). Monsanto Chemical Corp. (Clinton Laboratories) USPHS 1. Continuation of studies on the biological effect of slow fast and thermal neutrons on rats and mice. 2. Continuation on studies ont he comparative biological effect of penetrating radiation. 3. The effect of internally deposited plutonium on bone healing. 4. Cytological program on the biological effect of radiation on simple cells and tissue. 5. Instrumentation and techniques of radiation monitoring. - 5 - APPENDIX A (Cont'd) Monsanto Chemical Corp. (Dayton) New program being organized. 1. Biological effects following chronic exposure of animals to [illegible] by inhalation and parenteral administration. 2. Correlation between chronic exposure of works and polonium excretion rate. 3. Mechanism of action of polonium toxicity. 4. Development of special health physics technique for specific use in polonium purification. Los Alamos 1. Fundamental studies on the effect of acute radiation exposure. 2. Treatment of acute radiation disease. 3. Methods of detecting early radiation changes. 4. Metabolism of plutonium, U235 and other radioactive materials. 5. Detection of accumulated plutonium in the lungs. 6. Biochemical studies of nucleoprotein and the effect of radiation on the fundamental physiology of the cell. 7. Detailed study of absorption of plutonium from contaminated wounds. 8. Any special problems arising from medical hazards peculiar to this project. Western Reserve University 1. Investigation of the toxic effects of thorium and its isotopes. 2. Comparative studies ont he biological effect of external radiation and that from internally deposited radioactive materials. 3. Use of radioactive isotopes in fundamental biological research. These general titles are given inasmuch as a program has not been actively formulated. Contracts Awaiting Approval: University of Virginia - Dr. Alfred Chanutin Study of the effects of various types of radiation (alpha, beta, gamma & neutrons) on the circulating blood proteins by electrophoresis and protein fractionization techniques. To determine whether means of early detection of radiation damage can be accomplished in this way. University of Tennessee - Dr. Henry Wills Study to of the mechanism of toxic effects of uranium and other heavy metal compounds on the kidney. This is a continuation of Dr. Wills' work with the Rochester Manhattan Project during the war and contributes to that general study. - 6 - APPENDIX A (Cont'd) University of California, Los Angeles - Dr. Stafford L. Warren 1. The mechanism of blood vessel injury by radiation. 2. Bone marrow injury by radiation, its repair and treatment. 3. Mechanism of "metal" deposition in bone and mechanism of removal from bone. 4. Protein degradation following radiation and chemical injury. - 7 - APPENDIX A (Cont'd) I. General [Illegible] of Radiation The radiation encountered in nuclear fission as well as those encountered from naturally radioactive substances divide themselves into the following types: Alpha rays, beta rays, gamma rays and neutrons. Information available from the literature on previous studies indicates a rather extensive knowledge of the biological effects of X-rays and gamma rays and very little information on alpha and beta rays and neutrons. The programs were and are organized using the following basic outline: A. The Physical Measurement of Radiation of various types - Here it is necessary to develop methods of accurately measuring and standardizing the dosage of radiation to be used in the biological experimentation and measurement of the extent of any hazardous radiation which might be found in a plant area. B. The Biologic Effects of Radiation. Because of the known deleterious effect of radiation on the animal organism, it becomes necessary to determine the effect of controlled dosages of the various types of radiation on various animal species, so that such observations can be used in the control of possible human exposure. The types of biological effect possible to study are: (1) The Survival Time or percentage that the effect of a given dose will reduce the normal life span of different animal species. (2) The Genetic Effects of radiation as manifested in the development of abnormal individual types form changes in the hereditary mechanism. (3) Histopathological Changes as demonstrated by abnormal changes in the make-up of the various body tissues. (4) Physiological Changes produced by the alteration of the normal functioning of animal tissues following radiation. (5) Biochemical and Enzymatic disturbances which are the potential source of these physiological abnormalities. - 8 - C. Methods for the Detection of [illegible] are developed directly from observation of the above [illegible]. These include studies on: (1) Biochemical and Enzymatic Changes which may be detected and which, if measurable, can be corrected before irreversible damage that taken place. Examples of such change would be effects on the metabolism of coproporphyrin, excretion of abnormal substances in the urine and the like. (2) It has been known that radiation depresses the function of the hemotopostic system and detailed study is indicated to detect early changes under controlled dose radiation with all blood elements under continuous observation. (3) The Production of Anatomical Changes such as epilation, skin erythema, and alterations in the integrity of the skin and the like must likewise be studies under controlled dosage. D. Studies are likewise indicated on methods for the prevention of radiation injuries. These include: (1) Methods of physical detection of external radiation by the development of sensitive direct reading instruments capable of the detection of amounts of radiation well below those necessary for demonstrable injury to the animal subjects. (2) Methods for the determination of harmful amounts of radioactive dusts and gases in air, in water and the like. Many radioactive materials like radium are deposited in the body and in such locations produce injury to tissue. Methods based on the determination of dangerous amounts of these substances by examination of the excreta and direct measurements of the body itself are necessary. E. Protective Measures. Studies on the efficiency of shielding against radioactive materials, the efficiency of exhaust and ventilating systems against dangerous amounts of dusts, the development of protective clothing and devices, and the development of remote control processing methods have been extremely important in the Manhattan District protection program to date and will continue into the future. F. The possible therapeusis of radiation damage by the use of replacement therapy for the damaged bodily elements, as well as the reduction in the exposure following deposition of radioactive materials in the body deserves considerable study. Replacement of the damaged hematopoietic elements destroyed by severe radiation exposure offers one possibility; detection and neutralization of unknown toxic substances produced by radiation and other such difficult problems deserve consistent and detailed study. - 9 - All the above studies are necessary on alpha, beta and gamma rays and neutrons of varying intensity. In addition, the radiation from the radioactive substances to be discussed has [illegible]. Also, the effects of acute and chronic exposure must be determined because of their dissimilarity. II. Hazards Due to Special Materials For brevity it is preferable to discuss the potential toxicity of special materials by first indicating the type of study to be carried out, following by the presentation of those materials on which studies have been necessary. A. First, an actual determination of the toxicity of a substance must be made indicating how poisonous it may be in both acute and chronic exposure. In this way the toxic levels may be avoided in laboratory and plant environments. (1) The mode of entrance into the body by ingestion, inhalation and skin absorption must be studied as different manifestations and degrees of toxicity may be produced by each route employed. (2) A careful analysis must be made as to the character of the biological changes with the production of physiological, histopathological and biochemical evidences of damage incurred. (3) The nature of these injuries and the mechanism by which they occur must likewise be studies inasmuch as this affords information as to the necessary protection and indicated therapy after exposure. B. Preventative measures require study. (1) The effectiveness of physical methods for the removal of hazardous dusts, reduction in skin contact and prevention of ingestion must be measured, and methods for accurate determination of such hazards must be developed and used. The use of certain chemicals, ointments, and the like as protective measures must be studies as to their efficiency. (2) Protective devices such as respirators and clothing must be tested on required substances against which they will be used. (3) Finally, appropriate investigation of therapeutic measures to be used in the treatment of both acute and chronic poisoning states should they occur in industrial exposure must be made. Completion of all phases of the above program on a variety of substances provides complete information as to the medical aspects necessary to be considered in protection of the worker, prevention of injury and treatment of injury should it occur. - 10 - APPENDIX A (Cont'd) C. Substances on which studies of this [illegible] are necessary are: (1) Uranium and its compounds. a. Uranium metal and its chemical compounds, oxide, nitrate, chloride, bromide, tetra and hexaflouride, sodium, and ammonium sulfates. b. Uranium chain of heavy metals Uranium X1 Uranium X2 Radium Polonium c. fission products of cleavage of U-235 and plutonium. d. Artificial isotopes of uranium - 232, 234, etc. (2) Thorium and its chain (3) Plutonium (4) Special Accessory Materials a. Fluorocarbons c. Beryllium b. Fluorine d. Others III. Production Hazards The results of studies made on the materials discussed above are applied for the prevention and control of industrial hazards arising in the large manufacturing areas where these materials are used in large amounts. A. In the Electromagnetic and Diffusion Methods for the isolation of uranium 235 the major hazards are from the uranium compounds, the concentration of uranium X1 and X2, and the special accessory materials and by-products formed in the process of manufacture. B. In the graphite pile where plutonium (239) is produced on a large scale, the hazards are from the alpha, beta and gamma rays, neutrons, the plutonium metal and its compounds, the various radioactive fission products resulting from the pile operation. C. The chemical isolation of polonium following its formation in the pile incorporates hazards from alpha radiation following absorption into the body. - 11 - APPENDIX A (Cont'd) D. Study of the medical aspects of plan programs aside from the determination of the effect of radiation and chemical toxicity, include additional information obtained from plan investigations as from: (1) Clinical survey of all exposed personnel. (2) Monitoring of hazards by special instruments and methods. (3) Surveys of new types of graphite piles and production equipment. IV Hazards of Atomic Catastrophe in Production Areas A. Immediate Effects (1) Radiation - the radiation occurring at the time of the explosion coupled with blast and heat causes biological effects which may differ from those occurring following other acute known effects from gamma and neutron radiation, and demand study. (2) Blast - the blast of atomic explosion is so intense and may have totally different types of shock waves, recoil waves with other unique biological effects which should be investigated. (3) Heat - The intense burns from actinic type of radiation have not been studied. This also includes the combination effect of all three items in this group: blast, radiation and heat. B. Delayed Effects (1) Protective Devices - study of methods of protection against the radioactivity deposited at the time of blast. (2) Decontamination - methods of decontamination of soil and the like must be worked out for cleaning up active areas. (3) Investigative Equipment - special equipment must be developed and tested for use in investigating bombed areas. (4) Study of casualty effects - field study of fission clouds, possible injury to water supply, soil and the like, human damage by population surveys. - 12 - (5) Study of treatment of all immediate affects such as radiation, heat and blast. (c) Preparation of pertinent information in proper form for use by catastrophe units in production areas. - 13 -