Biology and Medicine Program - Contract W-31-109-Eng-38

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Biology and Medicine ProgfXUS3lW . BUDGET ACTIVITY NO. programs in this area and is closely correlated with relevant work of other governmental agencies ~ universities, and research institutions. ESTIMATED FOR FISCAL YEARS 1. MANPOWER AND COST DATA TEMPORARY PAID BY ANL TEMPORARY PAID BY OTHERS TEMPORARY PAID BY OTHERS TOTAL OTHER TECHNICAL TOTAL MAN YEARS 189.1 208.3 10.9 19.4 284.3 MATERIALS AND SERVICES 06-01 Interaction of Radiation and Control of Radiation Exposure to Man and His Environment 3,616 4,074 460 19 5,411 SeeFY 1973 Incremental Requirements explanation on page 8.

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REPOSITORY: OFFICE OF HUMAN RADIATION COLLECTION: PLUTONIUM INJECTION INVESTIGATION FOLDER: EXTRA COPIES FROM ROCHESTER FILES

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06-02 Assessment, Evaluation and Control of Radiation Expo sure to Man and His See individual 189 ' sfor detail. 06-01 Interaction of Radiation with -02 Assessment, Evaluation and Control of Radiation Expo sure to Man and His See individual 189's f o r detail. The following equipment items are for general use within the Biological and Medical Research Division and are,therefore, not allocated directly to Ste am Ster il izer Gamma Beam 650 Ir radiator Total General Equipment $6 2 Explanation of Equipment Items Ste am Sterilizer The Janus program requires animals free of pathogens: We are currently able t o provide these animals from our 1970 colony with but few exceptions. One o f these exceptions i s the general ENTEROBACTER contamination that currently exists in all animals in the facilities. trance into our colonies in the bedding. Attempts to eliminate it by autoclaving all incoming bedding have been unsuccessful. it by starting new colonies and to change to a different type of bedding. For This organism gained enW e now plan t.o el imina -added assurance, we will autoclave the new bedding.

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BUDGET ACTIVITY NO. It has long been apparent to us that we cannot prevent contamination of our stocks unless we effectively autoclave all incoming bedding and food. We have attempted to do this with our present facilities but we are unable to achieve sterility uniformly because the machine is not capable of pulling a high vacuum. W e cannot sterilize the food with our present autoclave because the machine is already running at capacity and because a high vacuum is manda - tory for such a procedure. vent total destruction of the vitamins.) (One must get the steam in and out quickly to pre - The revised program of the Division of Biological and Medical Research is focused in seven major areas. Mammalian Genetics, and the Metabolism and Toxicity of Fission Products in Dogs. The separately budgeted activity on Combating Detrimental Effects of Radiation is under the administrative management of the Biochemistry group These are Neutron and Gamma Ray Toxicity In I'Effects of.Radiation o n Living Organisms, " the effort in radiation toxicology studies with the exception of the program in dogs, in theoretical biology, in the Janus program, in cell kinetics, and in mechanisms of carcinogenesis is grouped into one o f the following three programs : effects of neutrons and gamma rays (neoplasia, degenerative diseases, and impair men to i physiological function) in the mouse and other rodents. plans are being made to enter dogs into the neutron irradiation protocol. Janus program, by comparing gamma rays and fission neutrons, is aimed at establishing results of value in predicting the effects of low level irradiation in small mammals, and eventually in man. An expanded toxicity program which hasas its primary aim the study of late

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budget submission, has three principal experimental facets: involving the aging of erythrocyte membranes, and immunological phenomena in mice and in dogs; studies on the comparative biology of rodents, particularly two species with similar physiological and anatomical characteristics but widely diffe rent lifespans ; and the testing of mathematical theories of mortality and the perturbations induced by radiation and other stresses. A new program in aging which is developing as described in the previous Each of the three major programs described above relates intimately to the others and in some cases personnel have responsibilities in all three areas ; e.g., reduction in lifespan (aging) and induction of tumors (radiation carcinogenesis) are the principal late toxic effects of chronic irradiation. aging are at comparatively early stages of development as compared to the Janu! program but new experimental approaches are being exploited; some p'romising leads are developing; and some important experimental work has already been accomplished. Activities formerly described as Laboratory Animal Medicine now for man integral part of several programs, especially those noted above. approaches: the biochemical basis for the modifying effect of phenobarbital on chemically induced hepatocarcinogenesis; the role of differentiation and other factors such as iso zy mes in cancer induction; and test systems involving skin carcinogenesis in hairless mice, the role of genetic factors in genetic defect A completely modified program in carcinogenesis which has three main It should be noted here that the study on the metabolism of fission products in dogs has developed into a primarily external radiation exposure program in whick the dog provides a n all important link between the mouse and man. Some studies must be made in a species longer lived than the mouse. Good liaison between the mouse and dog programs has been established, and interactions beneficial to both programs are developing. strains, and the potential of in vitro transformation in quantitating carcinogenesi: at the cellular level. Studies on a transmissible leukemia induced in an ir radi - a ted mouse for man additional new program in this area. A short discussion is also provided ona potential program in cell culture studies vis - a - vis radiation induced life shortening, carcinogen es is, and aging. The time is ripe to exploit recently developed culture procedures to enhance our understanding of fundamental mechanisms in these three processes. We have ideal c ir cums tak ces in which to prosecute such a program but limited flexibility in present funding to bring this about. A program involving several man years of effort could readily b e developed. Molecular and Cellular Level Studies include biochemistry and biophysics. The biochemistry program includes studies involved in the search for mechanisms of metabolic control: the kinetics, distribution and regulation of enzymes in m a m - malian cells ; physiological and biochemical studies on irradiated yeast ; and studies in plant physiology involving hormonal and metabolic aspects of radiation

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BIOLOGY AND MEDICINE PROGRAM BUDGET CONTRACT W-31.100-ENG-38 Biology and Medicine Program BUDGET ACTIVITY NO. ANL 60300 through 67400 Summary (BIM, CHM, ERP, The biophysics program has five well developed research themes which range from investigation of events a t the cellular level to those at the molecular level. The former includes one program on the radiosensitivity of cells (especially synchronous cells as a function of cell generation cycle position) and another on circadian rhythms in eukaryotic cells, Molecular level studies include de term i - nations of macro mo1ecu Iar structure using nuclear magnetic resonance spec tros - copy, X-ray crystallography, and chemical methods. methods to m e a s u r e stable isotopes of hydrogen, carbon, and nitrogen by gas chromatography and mass spectrometry provides a technique for the use of stable isotopes in clinical diagnostic procedures. A plan f o r clinical collaboration is now being developed f o r the exploitation of this w o r k in the diagnostic field. Development of analytical There are four projects in microbial genetics which utilize bacterial or viral s ys - tems to understand genetic mechanisms. lation of cellular DNA in E. c&, another the organization and function of the bacterial chromosome (of E. subtilis),a third the lethal effects of radiation, especially recoil nuclei, in the genetic material of E. c&, and finally a project on the genetic and physiological effects of ultraviolet and visible light. A smaller effort in mammalian genetics i s about to extend studies on radiation-induced sexlinked mutation rates in the mouse from single - marked systems to mutation induction studies with a double - marked X chromosome. One concerns the replication and reguThe project on the metabolism of fission products in dogs continues t o be revised, and is being coordinated with other external radiation toxicity programs in this Division. It is expected that these changes will r e s u l t in a productive effort which will contribute important information toward better predictions of radiation effect: in man. The program has been reduced in numbers of both personnel and dogs, while a t the sametime some experimental aspects have been enlarged. We are now concentrating on the external gamma ray exposure of dogs at levels presently down to 5 R/day and soon to r e a c h 2 R/day. essential baseline for the toxicity of the fission products cerium - 144 and This program will serve first as an The program on combating detrimental effects is now limited exclusively to the study of plutonium in animals, with emphasis on the distribution, metabolism, and toxicity of plutonium and its removal from the animal by chelating agents in conjunction with the polysaccharide glucan. Recent experiments with dogs have r e - vealed some striking differences in tis sue distribution between this species and

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cesium-137; and second as a vital link between the extensive external radiation itoxicity studies in the mouse to their eventual exploitation in understanding low I level radiation effects in man. needed t o conduct the low level radiation program and expansion of the prof es - s ional capability is needed in order to broaden the range of desirable investigations i n the dogs. Expansion of present irradiation facilities i s iT he major revisions of the overall Division program as outlined above, which ! were undertaken ayear ago, have already resulted in amore coordinated app roach for the Division’s research effort. Many formerly fragmented projects have been consolidated into a limited number of aims which have provided foci been preserved by their individual contributions to these aims. have many common elements, and effective collaboration among groups has Nevertheless, the independence of individual investigators has The aims also Loss of personnel due to reduced funding in recent years has limited the range of competences available to our programs, and a serious lack has been the loss of vitality resulting from the absence of new personnel and new temporary and post - doctoral visitors.Efforts to remedy this situation have already been successful in F Y 1972 with 16 postdoctoral appointees added. Our program can easily sup - port twice that number. Many of the newer studies still lack temporary appointees, and we continue to seek appropriate means to fund a larger complement. ::-. addition, graduate student programs have been developed further ; the 1971 sum - mer graduate program in radiobiology brought a substantial number of graduate students t o the Division for a limited time and subsequent research interaction with the universities resulted. We expect this t o continue and develop further with the 1972 program. Teaching and research affiliations with various universities in the area have bc,, expanded. The Division staff now hasa total of twenty-seven joint appointments with four universities, involving limited teaching assignments and substantial student and faculty interaction in research programs.These appointments continue t o develop in both the medical and the basic sciences, and contribute subst anti ally to a broadening of our research program. Relations with the academic community have been further strengthened with the developmept of student programs and visiting lecture series primarily in the AU universities via the AUA-ANL Biology Committee. This budget submission does not include any proposed work in support of the broadened role of the AEC with respect to all sources of energy, including nonnuclear sources.Nevertheless we have the basic competence, especially in late effects studies, the facilities and the willingness t o undertake appropriate toxi - cological o r fundamental studies in areas involving nonnuclear energy sources ‘! well. Additional funding would be essential since all our present personnel art fully committed to the work described above. The Radiological Physics Division has research programs in four areas : (1)in - tern al emitters,(2) land and freshwater environmental sciences,(3) atmosphe 1.

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Since funds fora new addition for the Center for Human Radiobiology, which were authorized and appropriated,were never released,some space within the BIOLOGY AND MEDICINE Biology and Medicine Program BUDGET ACTIVITY NO. ANL 60300 through 67400 Summary (BIM, CHM, ERP. The Land and Fresh Water Environmental Sciences program encompasses studie! of the distribution, cycling, and metabolic pathways of radioactive and stable ele - ments in terrestrial and aquatic ecosystems.Determination of the physical and biological effects of thermal discharges in the aquatic environment are included. The Atmospheric Physics Section investigates man ’ s immediate natural environment, the atmospheric boundary layer. changes in the lowest atmosphere brought about, either deliberately (as in the disposal of waste heat) o r inadvertently (as in increased urbanization) by larger scale human activities. Coordinated programs study those The Radiation Physics Section has initiated a new program on experimental studies of electron scattering, in addition to the ongoing studies, which include photoionization of gaseous molecules,luminescence of organic liquids, and theoretical studies. The electron - scattering studies not only pertain directly to the energy deposition from ionizing radiation via secondary electrons, but also com - plement photoionization studies and theoretical studies in the comprehensive understanding of dynamic properties of atoms and molecules.The unique s tren gt ‘ of this group stems from its intimate mix of theoreticians and experiment a lists and also from close collaboration with other molecular - physics groups within the The most urgent requirement of the Radiological Physics Division a t this time is additional suitable space.The Center for Human Radiobiology has recently addec a number of essential personnel and anticipates several more vital additions. At the present staff level, the division has been inhibited from requesting additional funds because of lack of space to accommodate the concomitant personnel and

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Laboratory is being converted for our use. ever, the present staff will b e inadequately accommodated and the desirable expansion of staff levels will be severely limited for want of suitable square footage, If the funds fora new addition are not forthcoming, the appropriation of additional Laboratory space maybe necessary to fulfill our programmatic responsibilities. Even with this additional space, howRequest for additional funds in F Y 1973 can be considered in two parts which are described in columns "A" and IrB" in paragraph6 of each budget activity number containing incremental requirements. Column "A" indicates amounts needed t o continue the BIM program in F Y 1973 at the payroll strength as of June 30, 1972, plus accepted commitments of personnel who will join inFY 1973 after that date. Also in this column are the require - ment s for a very minimum number of additional personnel who are considered essential to fill key research roles in the current research program as presently developed. These people fill needs in parts of the program which do not have enough assistance to keep up with the current workload. …