Biological Research at Brookhaven National Laboratory

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Although mos't of the investigations being carried aut at Brookhaven National Laboratory are in the realm of fundamental research, it is a postulate-of science that any new knowledge is valuable. Such new information can be used by the same investigator or by others in attacking specific problems of practical interest. In general, biological research at Brookhaven can be divided into two fields: (1) the study of basic biological problems by the use of radioactive tracers, (2) the study of the mechanisms by which radiation produces its effect on living systems. A6 E corollary to these main fields, work is also being done on the general improvement of methods and techniques for handling and using radioactive materials. The U s e of Tracers in Biological Experiments In general, mag's attack on disease and other problems of nature has followed a rather well defined pattern, First the observation of a given phenomena; next,an understanding of the cause, mechanics and results of the observed phenmena and, f W y , the development of methods bY which the phenomena <:an be controlled. The use of radioactive isotopes as "tracers" has greatly extended the ability of an investigator to observe various biological atoms as they engage in fundamental processes such as photosynthesis (the process by which plants utilize sunlight to By using these tracers, the scientist now is able to observe

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The tracer work now being done at Brookhaven utilizes radioisotopes produced at Oisk Ridge, The time required to get the material from O a k Ridge to Brookhaven has made it necessarg for us to limit our investigations to problems using the longer lived isotopes, When the Brookhaven reactor is completed, it is probable that greater emphasis w i l l be placed on problems requiring the use of short lived isotopes which can be efficientJy carried out only in laboratories near the site Tracer Studies on AnimalsStudies 8x8 being made of the uptake, distribution within the body, and use of va,rious trace metals, small amounts i n the food, and either known or suspected to be necessary for the proper functioning of the body. ants, asd fresh water clams have in common the fact that they are accumulators of one trace element, snanganese. their bodies maqv hundred or thousand times as concentrated stores of manganese as are present in their food, makes them suitable for the study of the chemical processes involved in such accumulations. both fKrm direct study of their treatanent of manganese and f r o m indirect study, by exwn-lng the differences in their treatment of other more or less similar elements, such as barium. These are elements, present in The animals being studied, hornets, This fact, that they incorporate within Data are obtained This latter investigation, using radioactive barium, has led to the discovery that hornets accumulate significant, though chemically subanalytical, amounts of this element. into the hornet by incorporating it into the insect's food. After a period 'Ilhe radioactive barium is introduced

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of time, the insect is sectioned and the location of the barium is determined by radioautograj?hictechniques. (Enclosed are photographs of a hornet being fed and several typical radioautographs.) Barfum is of interest both as being generally assumed strictly non-functioml in & d s , and as being one of the prominent radioisotopes in the uranium fission process. that hornet-accumulation of basium may provide a method of monitoring axeas for fission-product escape, at levels below the sensitivity of usual There seems to be a very real possibility A similar problem which w i l l be attacked in the coming season is that of rase-earth accumulation by hickory trees. This again is of interest both as an example of a most unusual phenomenon in trace element physiology, and in connection with fission-product monitoring. basis of some work done before the w a r , that rare-earth isotopes escaping along a drainage system, will be picked up @te efficiently by any hickory trees whose roots touch the drainage. It appears, on the The quantitative efficiency of this process, and its selectidty among the group of rare-earths, m e of great interest in connection with isotope disposal problems. Another program consists of the application of radioactive phosphorus as a tracer in the study of the part played by the various phosphorus compounds that are present in the tissues in the metabolism of sugars by the animali body. f i e l d and has led t o the formulation of what is known as the phosphorylation cycle, which describes the various intermediate steps in which phosphorUscontaioing conpound,sare formed and utilized in the conversion of the chdcal energy of the sugars into the energy for naintaining various body functions. A great deal of work has been done in this

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From early studies, it was established that the phosphorus compounds play a part in the resting metabolism of muscle, which appears to follow a different chemical pathway fron? the metabolism of muscular activity. The saae general type of experimental procedure using radioactive phosphorus as a tracer, has now been applied to the study of the position of these phosphorus colrpounds in the metabolism of the liver. obtained so far indicate that in this organ, in contrast to muscle, the phosphorus compoUniis 8.re of great importance in the utilization of sugars, These tracer studies e r e the basis for a good correlation between the enzyme studies and the probable metabolic pathway in the intact animal., It is planned to extend these studies on the liver to cover a wide range of conditions within the limits of normal physiology, and a l s o to certain pathologicisl conditions. to investigate are the effects on these phosphorylating mechanisms which result fromthe administration of the various hormones which are known to influence the metabolism of s q a r s , and to study the results of deficiencies in these hormones. the possibility that this type of experiment c a n yield a clearer understanding of the nature of the defect in the ability of the body to utilize sugars which constitutes the basis of the disease, diabetes mellitus. Among the factors which it is planned One important aspect of the latter is Another possible line of study to which this technique can be applied is in the study of the metabolism of the cancer cell. A further projected line of investigation to which this technique is adapted, is a stulily of some of the effects of radiation on the utilization of s u g w s by the body. There is some evidence from earlier work in

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the field that radiation reduces the capacity of the body cells to combine organic campounds, such as sugar derivatives, with the phosphate radical. L In other research radioactive carbon is being u s e d to study photosynthesis, the biological phenomena by which plants in the presence of sunlight manufacturle sugas from carbon dioxide and water. dependent upon this one reaction so a complete understanding of it is most Our research i n this field is two-fold. First, the plant c a n be used to synthesize sugars containing radioactive carbon ii' it is kept i n the dark until it has used up most of its sugar and is then allowed to photosynthesize in the presence of radioactive carbon dioxide in place of normal casbon dioxide. 1 of these sugms, glucose, fructose, starch and sucrose, is not feasible f by other means. These radioactive sugaxs can then be used as tracers in ' investigation of the :pathxagsby which sugar is changed to fat and protein. Second, we a r e investigating the mechanics of changing carbon dioxide to sugar w i t h the hope of some day being able to ca;rry out t h i s process without the plant. Another investigator is determining the distribution of radioLactive carbon in mice several months after they have been fed on a diet of it is hoped to find (1) which, if any, tissue of the mouse retains U s - proportionate amounts of the carbon (2) which, if any, chemical compounds of the mouse retain disproportionate amounts of the casbon, and (3) what a r e the effects, due to radiation, of the retention for EL number of months of considerable amounts of radioactive carbon in the tissues of the mouse. There has not been time to obtain any results but

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Inasmuch as the mice will exhale considerable amounts of radioactive carbon dioxide, it has been necessary to design the experiment in such a way that none of the radioactive carbon is released to the air. graph shows one section of the a l l glass system being used). - Work is also being done on the metabolism of iron by various pigments in blood. Irtthe past, much work has been done on the utilization of iron by hemoglobin, the oxggen carrying component of the blood, but little is known about its metabolism by other body constituents, Present ‘1 results indicate that one such pigment, cytochrome, uses iron in quantities comparable to that of hemoglobin. Another constituent in muscle, as yet ‘ unidentified, metabolized even greater quantities. It is suspected this is another pitgent cdLled myoglobin or muscle hemoglobin. r‘ Other studies using radioactive iron are being made to determine at what stage in its development it is possible for the erythrocyte, the red blood cell, to absorb iron. mature red blood cells of humans but the work being done here has shown that It is known that iron cannot enter the it can enter the mature erythrocytes of ducks, The duck cell is comparable t o the normoblast stage of the immature human red cell. therefore, that the iron must be incorporated into the cell either in or prior to the normoblatst stage. whether this is acconlplished by simple dif’fusion through the cell w a l l or It seems probable, Further studies axe being made to determine whether a more complkated biological process is involved. Biological Effects of Radiation There is a two-fold purpose in studying the effects of various ionizing radiations on living organisms. The way in which rgldlation produces Its effects on biological mechanisms is not w e l l understood and,

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in some c a s e s , little is understood about the way in which the mechanisms Any research into these questions will yield infomation in both Research now being done at Brookhaven is limited to the use of reiliation from x-ray machines and the various radioactive isotopes available from O a k Ridge. BrooMtaven are completed, it is expected that additional experiments will be started and present. experiments will be repeated or extended using other types and energies of radiation; i.e. fast m d slow neutrons from the pile, protons and electrons from the accelerators, etc. As the various machines now under construction at It is known that ionizing radiations may induce two radically different types of effects -- physiological and genetic. Physiological effects such as radiation sickness, in which there is interference with the various systems tlmt maintain the n o d existence of the organism are generally more innaediately apparent and, if they do not result in complete destruction or death of the orgaaisrn are usually temporary. Genetic effects are usually permanent because the hereditary determinants, or genes, are affected. functional patterns inherited by offspring of the parent organism, genetic changes usually do not become apparent until the second (or later) generation. Because the genes determine the structural and In v i e w sf the foregoing, it is easy to aee how the experiments described below fit jato the broad program of the Atomic Energy Committee. The research problems undertaken range from studies of t h e long time effects of various amounts of radiation to studies of the more immediate effects of doses of icadiation sufficient to produce severe physiological disturbance, injury or death.

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Effects of Radiation on Animals Investigations (using rats as experimental. aninui~s) are under way on some of the physiological responses brought about by whole body irradiation, in particular those involving the endocrine glands. To date, it has been sham tha-t when rats are exposed to x-rays, there is a great increase in their consumption and excretion of water on the day following by the amount of radiation they have received. designed to elucidate the mechanisms involved in these responses are now Their consumption of salt solution is also directly affected Experiments which are Particular (attentionis being given to the role of the adrenal is protected from radiation when the animal is exposed to x-rays. are two pictures showing the shields being put in place). tected have lived a significantly longer time after exposure to lethal doses of radiation than have unprotected rats. It is planned to similarly shield those other organs whose blood supply Kill permit this, the kidney, testis and spleen. These will consist of lining the shield with a radioactive isotope which will radiate the organ directly but w i l l not affect the surrounding tissue. Small lead shields have been placed around the adrenal so that it The converse experiment will also be done. Other investigators are studying the change in concentration of various constituents (ascorbic acid, cholesterol, ester and glycogen) of selected tissues (adrenal, liver, testes, etc.) . It is hoped that a better understanding of the phenomena mentioned above w i l l lead to an understanding of radiation sickness and thus to the development of a therapy for, or a preventive against, such sickness.

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Effects of Radiation on Plants Preliminary experiments have been made on the effect of various dosages of ionizing racliation on the growth and yield of potatoes, In addition to contributing to a better understanding of the mechanism of radiation effects, such experiments may, by mutation, also produce better - strains of potatoes. exposed to various x-ray dosages (75 roentgens to 38,400 roentgens) before doses of 130 r and greater. (The enclosed photograph shows this quite clearly). Above 4800 r very fev plants emerged and w i t h one exception they were very small r m d lacking in vigor. occurred even at the lower doses and decreased very rapidJy at dosages beneficial effect on germination and/or viability of the seed produced by the irradiated plants has been noticed. in potato breeding programs where difficulty is frequently experienced in obtaining viable seedlings. In the preliminary experiments "seed" tubers were It was found that delay in emergence definitely occurred with A small decrease in yield So far no mutations have been observed but a potentially This effect may prove valuable Several genetic lines of corn are also under study. Corn has been chosen because there is already so much b o r n about its genetics and cytology that it is ,an unusually useful tool. Several hundred hereditary characters, distributed over the 10 pairs of chromosomes, are knoxn in corn, Cytologically the 101 chromosomes are sufficiently different in their morphology that they can each be identified. on the chromosomes …