Attachment AEC 604/35 August 4, 1958 COPY NO. 61 ATOMIC ENERGY COMMISSION PLAN FOR EXPANSION OF RESEARCH IN BIOLOGY AND MEDICINE Note by the Secretary The General Manager has requested that the attached report by the Director of Biology and Medicine be circulated for consideration by the Commission during the week of August 11. W. B. McCool Secretary DISTRIBUTION COPY NO. Secretary 1 Commissioners 2 - 6,67,68 General Manager 7 Asst. Gen. Mgr. 8 Asst. Gen. Mgr. REID 9 Asst. Gen. Mgr. Adm. 10 General Counsel 11-14 Biology & Medicine 15-34 Congr. Relations 35 Construction & Supply 36-38 Finance 39-41 Industrial Development 42-44 Information 45-46 Inspection 47 Licensing & Regulation 48-50 Military Application 51 Operations Analysis 52 Org. & Personnel 53-54 Production 55-56 Reactcr Development 57-59 Research 60 secretariat 61-66 - 1 - The Hearings dealt with the technical subject matter that fallout is concerned with and dealt also with the adequacy of the biology and medicine research program in this field. 4. The Atomic Energy Commission's research program administered by the Division of Biology and Medicine has bean designed to meet its responsibilities as outlined above. The growth of this program, as reflected in the level or financial support, is shown in paragraph 2 of Appendix "A"ù As of June, 1957. it was estimated that about two-thirds of the program related to questions of the biological effects of radiation and of biological hazards. In retrospect, it is the judgment of the Division of biology and Medicine that this program has been developed at a reasonable rate. except in the construction of facilities, the effort put into the program generally has not been severely limited by the availability of funds. More fundamentally limited have been such things as the availability of scientific talent and facilities, the continuous dependence of program planning on the state of knowledge and technique at the time or planning, and the fact that many biological studies characteristically involve long-term biological processes that cannot be greatly accelerated. 5. Expanded development of the AEC program in the field of biological hazards of radiation must be considered in the light of existing budgetary policies. Without special consideration and support by the Commission, leading to some assurance of the financial level of the program to be anticipated during the next several years, the Division of Biology and Medicine finds it inadvisable to initiate desirable long-range studies that would be of little or no value if terminated too early. - 2 - 5-Year FY1958 FY1959 FY1960 FY 1961 FY 1962 Total (in thousands of dollars) e $36,300 $36,300 $36,300 $36,300 $36,300 $ 181,500 Expansion over Base 1,600 6,700 17,200 22,400 25,100 73,000 __________________________________________________________________ Total Research $37,900 $43,000 $53,500 $58,700 $61,400 $254,500 Construction -0- 2,000 5,000 2,500 1,000 10,500 __________________________________________________________________ Totals $37,900 $45,000 $58,500 $61,200 $62,400 $265,000 _________________________________________________________________ STAFF JUDGMENTS 9. The Division of Finance and the Office or the General Counsel concur in the recommendation contained herewith. CONCLUSIONS 10. It is concluded that a. The responsibilities of the Atomic Energy Commission in the field of radiation biology, from the standpoint of the biological effects and hazards of radiation, require the development of related information at an expanded rate that is not primarily limited by a need for funds; and b. Approval for planning purposes of the program proposed for biological and medical research over the next five years is necessary to the long-range planning required to enable the AEC to discharge its responsibilities in this field. RECOMMENDATION 11. The General Manager recommends that the Atomic Energy Commission: a. Approve for planning purpose of an expansion of the biology and medicine research program according to the schedule given in the Table in paragraph 8 above and as shown in Appendix "B" and detailed in Appendix "F"; b. Note that the proposed 5-year program will be used as a basis for preparing budget estimates of the Division of Biology and Medicine; however such future budgets will be subject to the normal budgetary reviews within and outside the AEC; c. Note that a letter such as Appendix "D" will be sent notifying the JCAE of the approved expansion program; d. Note that the proposed expansion program is based on more detailed planning summarized for information in Table II, Appendix "B"; - 4 - APPENDIX "A" BACKGROUND AND DISCUSSION 1. Since its inception in 1947, the AEC has sought to meet its responsibilities in the fields of radiation biology and medicine by developing a well balanced program or research with the following specific objectives: a. To exploit the use of nuclear radiations and of radioactive materials in Studies of basic biological processes, with emphasis upon those recognized as being especially urgent in the interest of human welfare. b. To increase our knowledge of the biological effects of radiation, both from the point of view of empirical relationships between radiation dose and radiation effect and from the point of view of understanding the mechanisms by which radiation injury is produced. c. To obtain information useful in the control of biological hazards or radiation, either through minimization of exposure or reduction of the biological effects. d. To improve and develop techniques for the use of radiations in medical therapy. e. To develop and encourage the use of radiations and of radioactive materials in agricultural research. 2. The following table gives the year-by-year dollar operating budget since 1948 for the biology and medicine program. It can be taken as a measure of the growth of the program itself. FY 1948 $13.2 million 1949 14.6 1950 17.7 1951 20.6 1952 23.9 1953 24.9 1954 24.9 1955 26.8 1956 28.9 1957 31.5 1958 37.9 The development of nuclear weapons and the rapidly expanding development of nuclear reactors have been accompanied by increasing public concern about the possible immediate and - 6 - 6. Certain general areas for needed research were suggested on page 18 of the "Summary-Analysis:" "1. The behavior of particulate matter in the atmosphere, particularly the stratosphere; "2. The absorptive capacity of the biosphere for fallout products such as strontium 90; "3. The selectivity of biological systems for particular isotopes; "4. The response of biological systems to low doses of radiation; "5. The application of biological knowledge obtained from an experiment on an individual to large populations and vice versa. 7. For additional background information, Appendix "C" is a letter from the Advisory Committee on Biology and Medicine concerning the Division of Theology and Medicines research program. 8. Appendix "B" sets forth the Division's plan for an appropriate 5-year expansion of the Commission's Biology and Medicine program and which is detailed in Appendix "F". - 8 - 3. The study of the movement of radioactive materials through a cycle in nature will be pursued with assurance of reducing uncertainties to acceptable limits. Measurement techniques of trace quantities of radioactive elements in the environment either are already refined or give promise of becoming so. An exception to this is the measurement of the stratospheric air concentration of Sr90 and other isotopes; much remains to be done before reliable measurements can be expected routinely. 4. Measuring low-level effects of radiation is difficult to do in a refined way because these effects only show up on a population; i.e. in a statistical sense. The key question is the relationship of incidence of effect to level of dose at doses far below those producing observable effects in a single arbitrarily specified individual. A key question in radiobiology is how to make extrapolations from the laboratory animal (fly, mouse, rat, monkey, dog) to man. It is expected that proposed expanded studies with large animals will add to our knowledge of how to do this. 5. Uncertainties in effects of radiation on human genetics range from comparatively straight-forward studies (at "high" doses) of the occurrence of observable mutations in early generations to the very difficult problem of estimating the over-all impact of increased rates of mutations on future generations. Some of the genetic problems can be solved by careful experimental studies on lower forms, in that the principles of genetics apply to all life forms. However, the answers to certain critical quantitative questions can be secured only by studies of the genetic behavior of man himself and AREAS OF EXPANDED RESEARCH - SUMMARY BIOMEDICAL PROGRAM TABLE II FOR REFERENCE SEE (3bb03) "The ACBM believes that the various programs should be expanded as planned, and rinds the dollar amounts realistic and considers adequate manpower to be available.... "....Time has not been available for detailed consideration or individual projects.. . "We recommend that the Division continue its scrutiny particularly of the older and continuing types of research projects to assure adequate return and appropriate pertinence to the AEC's mission. Cooperative progress with other agencies and Divisions as with the NSF on education, the USPHS on environmental hygiene, the Department of Agriculture on the up take of radioactive material by plants, and the Division of Reactor Development on waste disposal, are of mutual benefit to the scientists involved and provide significant savings for the taxpayer. "There are no obvious omissions in the program, but there are some categories which have been undertaken because of the urgent need and because no other group was prepared to support them. Among these are certain phases of oceanography, of geophysics, and of blast studies. It is hoped that the Commission may be able to transfer these important but somewhat extraneous activities to more appropriate agencies in order that the DBM may concentrate on the areas or to primary responsibilities." Sincerely yours, /s/ Shields Warren, M. D. Vice-Chairman, Advisory Committee for Biology and Medicine Mr. L. L. Strauss, Chairman U.S. Atomic Energy Commission 1901 Constitution Ave., N. W. Washington 25, D. C. AREAS OF EXPANDED RESEARCH - SUMMARY BIOMEDICAL PROGRAM TABLE I TABLE II FOR REFERENCE SEE (3bb04) APPENDIX "F" DETAILED EXPLANATION OF PLAN AND COST ESTIMATES (In thousands) 5-Year 1.a Radiation FY 1958 FY 1959 FY 1961 FY 1962 TOTAL Effects... $ 760 $2,185 $8,500 $9,000 $26,445 (1) Studies on Internal Emitters, Including Sr-90 in Animals: Present knowledge of the cancer-producing and life-shortening effects of Sr-90 is not adequate. Previous studies have been for the most part confined to small laboratory animals. Long term studies in longer lived animals using small doses of radium, Sr-90 and other fission products are needed if we are to arrive at a more precise estimate of the hazard to the human population. These studies on internal emitters in animals would be centered on experiments on dogs and monkeys. This would assume expansion or the existing projects, such as the University of Utah and University of California, to the full extent of the present facilities. Since the life spans or the larger animals range between 15 and 20 years, it is imperative that the experiments be set up as early as possible in order not to delay further the obtaining of some of the most critical information, namely the concentrations of radioisotopes, at which only negligible effects would be produced (such as minor aberrations in bone structure unaccompanied by malignant change) or at which the chances for grossly detectible effects would be so insignificant statistically as to be acceptable by all. Plans for such studies are well developed, but putting them into effect is dependent on construction of animal facilities; because the animals will have received substantial doses of long-lived radioisotopes, it is necessary to provide facilities which are able to control effectively the dissemination of radioactive contamination. Present preliminary problems, both basic and clinical. By receiving an appropriate -geographic distribution or these instruments over the nation, it will be possible to assist biomedical personnel in evaluating claims of internal contamination as well as being of critical utility in the event of a reactor accident or other type of dissemination of radioactive materials. The usefulness of this type of instrument in facilitating study of the metabolic turnover of gamma emitters in man will add tremendously-to our knowledge of the internal emitter problem and to medicine in general. (3) Epidemiological Studies of Life Span and Leukemia in Humans There seems to be no way of attacking the problem of life span and Leukemia in man in relation to radiation dose except by conducting well-planned epidemiological studies. It will be. necessary to secure the services, on loan or other, of a top-notch professional epidemiologist and give him an adequate staff and the necessary mechanical aids. Projects will be developed along these lines in conjunction with the U.S.P.H.S. (4) Fundamental Effects of Radiation at the Biochemical Level: The research program carried on during the past few years has produced results which indicate that both primary and secondary biochemical changes, following the absorption of high energy radiation in biological material, occur in substances of very high molecular weight. At the present time the chemical and physical approaches to the study of such high molecules weight compounds are entirely inadequate to provide an understanding of the precise mode of interaction between radicals formed by radiation and the compounds themselves. A rational treatment to reverse the effects of radiation, or to prevent them depends upon a full understanding of these processes. Some additional objective procedures giving information on behavior performance of the central nervous system during and after radiation in addition to study of the Gestalt patterns. (6) Biological Effects of Heavy Particles: There is good evidence that energetic-charged particles of mass considerably greater than protons or helium nuclei are found to exist in the upper levels of the earth's atmosphere. There is some evidence that shows that these heavy primary particles may result in a different kind of damage to biological systems than those that have been studied up to the present. The assessment of the radiobiological hazards associated with space travel may be extremely important in determining the future development of all of mankind, as well as our own nation. Although accelerators do not exist at present which are capable of producing particles of equivalent mans and energy as these particles from outer space, several new devi (HILAC) have been completed recently that are capable of a accelerating ions up through mass 44. Support should be given to interested scientists to utilize the radiations produced by these instruments for biologic testing and experimentation. In addition, a program should be initiated to provide for some biological work with all new supervoltage devices. As most of these devices are all located ar planned for at sites with more or less extensive radiobiology programs, increased requirements for space and personnel would be at a minimum. In the normal course or life, the operational efficiency of complex organisms is lost progressively with time -- a process called senescence or aging. Recent findings demonstrate that acute or protracted exposures cause such degenerative changes to occur earlier than would be the case normally, also that the amount of premature aging and the earlier time of occurrence of death which takes place as a result, increases with dose. As yet it has not been determined whether natural and radiological aging are additive nor whether there is a relationship between natural radiation and the average length of life in different species. Studies involving the whole lives of larger animals are costly both in terms of funds and manpower. It is anticipated that at least some significant investigations can be carried out with smaller animals and with microorganisms and tissue cultures, but it is necessary to verify and supplement such findings by investigations with larger animals, especially those having characteristics in common with human beings. Certain data accumulated for other purposes, it is believed, can be analyzed and interpreted to elucidate features of a radiobiologic aging. Moreover, certain of the long-term radiation toxicology investigations may be expected to yield useful results, but various specifically designed experiments with different types of animals are needed. 1.d Farm Animal Study 5- Year FY 1958 FY 1959 FY 1960 FY 1961 FY 1962 TOTAL Research Projects.... $60 $ 240 $ 1,700 $ 2,000 $2,600 $6,600 Statistically significant studies concerning the effects or whole body irradiation of animals as large or larger than man have not yet been accomplished. Data so far have indicated that large species differences exist. Since the effect of total body irradiation of man, and most particularly the mechanisms of damage and recovery, depend upon extrapolation of experimental data, there is an urgency in these investigations. Fertility, a reproduction and resistance to disease or response to stress are indications of vitality of the individual, breed (race), or species. There are, therefore, parameter. of investigation other than death by which total body effects should be evaluated. How much fission product contamination is to be tolerated either in peace or in war in animal organisms depends on the biological effect of the fission products in low concentrations present over a long period of time. Although some work is underway to evaluate objectively the extrapolations used at present from relatively acute high levels, the number of experiments of this sort on long-lived animals of large body weight and a growth pattern comparable to man are limited to one study of significant numbers, and several investigations with small numbers of animals. These studies are not extensive enough. Physical and physiological factors such as the chemical form of the contamination and characteristic of normal lactation (when demineralization of milk comes occurs as opposed to when mineralization of milk comes primarily from food etc.) may provide extremely important factors to be considered in establishing limits of contamination and biological damage. Factors found to be present in milk which increase discriminate derived from livestock experiments designed to test effects in relation to human health, as our chief sources at information. We will continue to take advantage of these investigations as our chief source of information. However, because of the importance of animal health to our national economy and well-being, we should initiate studies to test tolerable levels as they pertain to different species of livestock. Such studies will produce objective results from which the limitations or readjustments of animal production might be made in a radio-contaminated environment. Variations due to metabolic rates, life span, fetal development, and feeding habits (omnivora or herbivora of grazing or browsing habits, etc.). The results of such studies, in this case primarily designed for the effects of animals (some of which maybe prone to such limiting factors as leukemia or sarcoma, to which others may be insensitive) will add to the understanding of radiation effects in humans as well. Species 2nd varieties of crops which would absorb only-relatively small quantities of radioactive contaminants from the soil would reduce the hazard of food contamination. Plants, either natural or cultivated, which would selectively absorb one or more important contamubants, e.g., strontium 90, to a high degree, might serve as a means of decontaminating land by repeated cropping and discarding. It is known that plants differ as to their requirements and content of nutrient and non-nutrient elements, some of them absorbing certain microelements to the extent that they are called indicator plants. Systematic search and experimentation should be conducted to locate natural, and cultivated plants which might be utilized to reduce food contamination or to decontaminate soil. Following deposition on land, fallout and its constituents are subject to surface transport in soil and water, depending on the topography, soil characteristics, and environmental fact. Some of the radiostrontium in fallout deposited on upland may sooner or later reach the lowlands' and increase the concentration of strontium in the soil there. After a uniform heavy deposition of fallout within a topographic unit, such as a subsequent movement might result in a significantly lower concentration of strontium in the upland soil and therefore a relatively less contamination of food crops. Determination of the presently low, but measurable strontium 90 content of soils at different elevations and locations within a number of valleys, basins, and other topographic units should be made in order to be, able to predict the areal non-uniformity of soil strontium in time after a heavy deposition of fallout. Considerable research has been conducted in recent years on the extent of absorption, translocation, and accumulation of fission products and fissionable materials in plants. Much of 5-Year FY 1958 FY 1959 FY1960 FY 1961 FY 1962 TOTAL 2.b Environmental Research.... $ 80 $ 535 $2,000 $2,000. $3,300. $6,915 Contamination of environments by fallout and waste disposal generate long-time biological problems -- long-time because of the nature of the approach to landscape biology and because of the low-level radiation which may require generations to produce visible effects. It is important that biological criteria be determined for establishing the extent and nature of contamination in the field --- i.e., are there biological phenomena that reflect biological contamination of the landscape? This question is at a present unanswered. The specific programs in ecological research that need to be established or expanded include the following: (l) A long-time program devoted to landscape biology at on site locations - Argonne, Oak Ridge, Savannah River, Hanford and Idaho. This program will include a listing of the plants and animals that make up the natural populations at the study sites and an assessment of the environmental conditions. Observations on the effects of radiation on natural populations will provide a better basis for an understanding of radiation experiments with laboratory animals. For animals in the study sites, trends, periodicities, and fluctuations in radiated and less-radiated areas need to be determined in terms of numbers, litter size, life span, reproduction, migration, and the like. Similar data are needed for plants. These data cannot be obtained by laboratory experiments. (2) A long-time program devoted to landscape biology at off-site locations that include the major soil types and the major vegetation, climatic, and crop regions of the United States. (6) A program devoted to oceanic surveys to determine fate of radioisotopes in the ocean. The oceans contain radioisotopes created by weapons tests and by the disposal of radioactive wastes. As some or these radioisotopes may find their way back to man by way of the food chain or effect man's use of resources of the sea the physical and biological fate of radioisotopes in the ocean is of concern. Presently contamination in the ocean is principally from weapons test and is not great but within the near future disposal of wastes from nuclear fission power plants may greatly increase the levels of contamination. Sufficient knowledge is not now available to predict the effects of high level contamination in the ocean but an adequate, long-range program of research on the biology of marine organisms and complemented by research on the physics, chemistry and geology of the sea can provide the necessary information. (7) A program devoted to oceanographical radio- biological surveys associated with the Pacific testing program. A program that provides a vessel that is adequate to make plankton tows and mid-water trawl hauls and to take water samples and bottom core samples is needed to replace the crash programs of the put for which either no or inadequate facilities were provided. Such a program carried on previous to and following each testing program will provide information on the residual and fresh contamination in the ocean in the vicinity of the test site. An important facet of this program is the evaluation of the contamination of the fish in the Central and Western Pacific, an area which is heavily fished for tuna by the Japanese. A fishing program, or preferably a sampling program of the Japanese fishery are the proposed methods of obtaining data to evaluate the problem. 2.c. Fallout Sampling and Analysis 5-Year FY1958 FY 1950 FY1960 FY1961 FY1962 Total 0 $ 1,100. $2,700. $4,000. $5,300. $13,000. The over-all objective of this portion of the program is to evaluate the physical factors which relate the radiation exposure at humans to the testing end use of nuclear weapons. The magnitude of the problem, encompassing variable features of the earth and the atmosphere on a world-wide basis, limits the degree to which it is practical to establish detailed relationships. Although marked progress in this field of study has been made during the past four years, there remain substantial inadequacies at information on the following elements of the problem. (l) what fraction of observed fallout is derived from high-yield tests via an extended period of storage in the stratosphere? (2) To what extent is the observed large geographical variation of fallout as represented by analyses of soil, gummed films or rain water over the world due to: (a) errors of sampling or analysis (b) locations of nuclear weapon testing sites (c) random small-scale variations at terrain and weather in the vicinity of the sampling sites. (d) large-scale variations in rainfall (e) variations in the transfer of stratospheric air into the troposphere (f) variations of the concentration of radioactive debris in the stratosphere. (3) For any particular test how are the fraction stored in the stratosphere for a period of years and the fraction falling out within weeks or months related to the yield and other characteristics of the test? The three lines of attack on these problems which are now being followed, and the ways in which expansion or these are planned, are outlined below: of the biomedical program. There are four areas in which these developments are indicated: a. Research in the development of new basic principles in detecting and measuring radiation is needed for increase sensitivity and accuracy. b. Electronic amplifiers, analyzers, data processing and information presentation equipment and systems are needed for the accurate and rapid analysis of radiation data. c. Developments of equipment for identifying measuring and analyzing trace amounts of the various radioisotopes occurring in the food chain and in vivo will continue to be required. d. developments in the design and form factors Of dosimetric instruments are required for the measurement of radiation doses from external and internal emitters on the various systems and compartments of the body. Specific research projects to be initiated or expanded: (a) A new principle in solid detectors analogous to the geiger counter shows sufficient promise to merit additional research (b) A basic study in the mechanism of scintillating materials will be pursued to assist in the development of more sensitive low level scintillation counting equipment. (c) Similarly, continued development of photo-multiplier tubes for use with 10 level counters will be pressed. (d) An automatic scanning devi in association with an electronic computer and data reduction system for counting bi-nucleated lymphocytes as a measure of whole body, exposure would be studied. (e) Present work in the development of tissue equivalent plastics and ionization chamber a dosimeters will be stepped up. (f) Development of low level so beta gas counting tubes will continue at an increased rate. 4. Civil Effects Test program 5-Year 5-Year FY 1958 FY 1959 FY 1960 FY 1961 FY 1962 Total $ 200 $ 500 $1,000 $1,000 $1,000 $3,700. (a) prompt Neutron and Gamma Radiation studies. It is proposed to expand the already planned study a neutron and gamma radiation from nuclear weapons in order and ,animal will require the construction of a number or facilities not otherwise available. These would include, but not necessarily be limited, to: a (1) Dog holding facilities providing holding kennels, runs, disposal units for waste materials, radio-biology and analytical laboratories, etc.; (2) large animal areas (cows, sheep, goats, swine, etc.) providing fencing, shelter, waste a disposal units, and laboratory and office space; and (3) development and fabrication of whole body counters for use with human beings and large animals, with heavily shielded enclosures of steel or brick, and, counting equipment, including crystals and multi-channel analyzers. Relative to the need for whole body counters, at the present time the study of low-level strontium work is limited by the facilities, technicians and time necessary to chemically separate and prepare samples for chemical analysis. Depending on the precision required, the costs per sample now range from $75.00 to $500.00 each. For efficiency of scientific personnel and economical operation, whole body counters (or at least large gross counters which will enable counting or disintegratic particles or photons in whole bones, etc.) would add greatly -- in fact they might be the most significant factor to the speed-up of this work and will certainly be an over-all factor in reducing cost per experimental sample. All such counters in use at present are in operation 100 per cent of the time and none reducing cost per experimental samples All such counters in use have been specifically available for large animal work. In order to carry out experiments in fields of relatively high accumulative doses of radionuclides, unique but adequate facilities must be provided, whether on government or private property. The buildings and area are not safe for other purpose for a considerable period of time. The biological effects of chronic low level internal radiation, whether due to strontium-consuming compared with normal laboratory operations. Unfortunate dosimetry in the past field programs has often proved to be unreliable, resulting in additional uncertainties in the interpretation of the data. It is proposed that a source of prompt nuclear radiation be constructed for the specific use of research team of radiobiologist and geneticists. There appear to be designs of flash reactors that could provide a neutron flux of the desired duration and intensity. The design concept is considered to be inherently sat e. However, because of the unproved nature of the construction and operation, location of the device would be restricted to one of a few Commission-owned facilities. There are other practical applications of a flash reactor in the Division's program, such as a source or neutrons for neutron-capture therapy and the production of short-lived useful in trace element analysis or medical diagnosis. Construction costs would amount to about $2,000,000 and will be included in the budget estimate for FY 1960.