Oak Ridge Institute of Nuclear Studies Twelfth Annual Report Operating Under Contract with the U.s. AEC

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Oak Ridge Institute o f Nuclear Studies OPERATING UNDER CONTRACT Unite d.. State s.. Atomic Energy Commission

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EVER a lethargic organization, the ORlNS Medical Division has completed a particularly active Nyear-in theory and in practice, at home and ' abroad, in the laboratory and the hospital. Programs inthe germinal stage last year came to full flower, lo replace or take precedence over others being brought to successful conclusion. And, of course, there to the intricate but routine tasks of keeping a complex organization functioning smoothly in a l l phases of its Much of the work of the division h a s been directed toward the clinical effects of significant doses of radiation on living organisms. As early as June 1955, staff members had stressed the necessity for extensive modifications of existing procedures to take care of potential radiation-accident victims. Many of the division's varied programs tie in to this particular The bone-marrow-replacement program, started rha h e r 1955, i s an excellent example of the type of study that is significant not only in the treament of disease but as an immediate and direct application to the treatment of radiation-accident cases. Dosimetry studies, too, have an important bearing. Much of this program is related to the level of radiation that i s most probable in a serious accident, and the level at which treatment is most necessary because it i s most useful. In essence, the situation i s this: Where patients have been subjected to extremely high levels of radiation, there is at present no successful method of treatment known, except for palliation of incidental complications. In the rang6 of less than 100 roentgens, there is nothing that has to be done-patients will almost invariably recover from any physical effects incidental to the exposure. But in the very important, just sublethal range, there are procedures possible for the patient by which the lethality of the dose of radiation may b e considerably reduced. In June, the Medical Division was suddenly given the task of caring for eight persons exposed to large 'doses of radiation. Three were dismissed within a few days when it became evident that they had received less than 100 rads. Five of these patients were in the 300 to 400 rad (radiation absorbed dose) range-the range which may or may not be lethal, in which medical care i s most necessary, and about which knowledge i s scarcest. Further details of the case are given later in this report; a complete interim report on the medical care of these patients is i n the process of pubA great deal of the division's effort during the year has gone into the training program. The use of radioisotopes i s now so widespread that specific radioisotope methods are being modified and adapted to innumerable types of routine hospital uses. The necess i t y for training physicians in the use of radioisotopes i s beginning to reach urgent proportions. Because of the increasing demands on overtime for the instruction of foreign and domestic visitors at the Medical Division, its training program i s undergoing changes to make it more efficient in the future. An unusual number of publications have been produced by members of the division during the year. Some of these are necessary reports, not strictly classed as publications and not in the open literature; some are teaching materials that are distributed only to students of the division; and some are holdovers from the previous year's work. Improvement of scanning techniques, both in performance and interpretation, i s a continuous program of the division. Proper interpretation of scans has been characterized as an art, not a science, so every means of making scanning more accurate i s of extreme importance to 'every physician using radioactivity i n his Routine area scans have been continuously used, particularly in patients with thyroid disease and liver metastases. Particular interest in the group of patients .with thyroid remnants or areas of functioning tumor has been advanced by repeated scanning studies. Ryosaku Tanida, resident in experimental medicine, has been carrying out a special study with a liver phantom in an effort to determine the size of

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nodules that can be detected b y external counting techniques. This study i s continuing. It has been found that in studying patients with thyroid carcinoma previously treated b y total or nearly total thyroidectomy, the use of large test doses of five or ten millicuries adds significant information over that obtained with usual tracer levels. Interest has also been shown in some special areas of activity in the teeth, salivary glands, and other areas not normally seen by scanning. The profile scanner, which uses a battery of scabning devices to traverse the entire length of a patient, has undergone testing during the year. It has been used only to a small extent in clinical problems, but has already given pro.mise of helping to evaluate the total distribution of radioactivity in a patient. It elirninates the great depth dependence of the area scan, and makes possible scanning of the whole body without requiring the patient to lie still for an excessive length of time. The great bulk of work with the profile scanner has been devoted i o experiments with samples to determine such characteristics as field of vision, uniformity, and cut-off points. Work i s also in progress on a device to explore its response. At the end of the year, work was in progress on the construction of a three-dimensional isoresponse model for the scanner; it will serve as a standard for future investigations and for the proper operation of the machine on patients. It i s hoped that the profile scanner may be made quantitative, because more and more interest is being given to the quantity of radioactivity in a person's body. Present levels are exceedingly low, but the The Medkal Dkision's human linear scanner. question of fallout has caused more persons to beco%; interested in determining the exact amount; if prete * possible to determine the total radioactivity in a per.! son's body by passing him beneath it. In the courie: of this study, the radiation victims of the Y-12 acciden;? work on the profile scanner is successful, it may b,y were scanned by the device. .r Research associate Akiro Tsuya has devised " ings of the field of vision of a scanning head or other5 detecting head. The method provides only an approxi. 3 mate answer, but it has the virtues of being automatic, ? provides a visible record, and can be done in a few method of getting very roughly quantitative record.a :; Another scanning problem under investigation i s , that of "background erase." The investigation includes 1 not only the question of the best method of erasing background, but also whether such erasing i s desirable. Such desirability will be investigated along with the quest for a practical erase circuit. Special studies were begun during the year on the early uptake phase of radioactive iodine-131 in normal and hyperthyroid patients. Principal objective is the improvement of methods of obtaining early uptakes. By taking advantage of previous work done on the correction for neck background, and using a continuous recording device, staff members have been studying the effects of varying doses of drugs such as stable iodide and potassium perchlorate on thyroid physiA most active program in the Medical Division is that concerned with total-body irradiation and bonemarrow transplantation, Further detailed studies have been made on biochemical changes and changes in morphology of bone marrow in patients with leukemia after a single massive dose of total-body irradiation. Bone-marrow transplantation h a s been attempted according to methods previously developed in the MediAlthough some temporary favorable results have been obtained in children with acute leukemia, it is not felt that true transplantation has been clearly demonstrated. It is possible that some blast-cell leukemias respond to a single large dose of total-body irradiation with a suppression of the leukemic proca and reactivation of normal blood formation. mom

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are now under way to determine the true place of the bone-marrow injections in thii sequence of events. In patients with subacute granulocytic and monocytj* leukemia, in the adult age group, no favorable have been attained, although transient depression of the leukemic process has ben demonstrated. During the past year, the division has improved its facilities for delivering total-body irradiation with cobalt-60. A special simple shielded source allowing a wide-angle beam distribution has been set up, and, in teletherapy machine has been used for this type of During the year, considerable effort went into the development of methods for platelet separation and storage. Platelets are essential for treating the period of marrow aplasia following the massive irradiation. Biochemical studies have tried to characterize the results o f the tissue breakdown, which i s so striking immediately after these large doses of radiation. It i s obvious that in leukemic patients, because of the large volume of highly sensitive cells, this tissue breakdown may be much more extensive and profound than might be expected with a similar dose to a normal individual. The radiation accident, which occurred at Y-12 on June 16, occupied the clinical staff of the Medical Di i for the rest of the year, and i s continuing to require major effort. Extensive studies of blood and bone marrow and biochemical changes in the blood and urine were initiated as soon as the patients arrived at the hospital, and have been continued to the present. During the early period of care of these patients, serious consideration was given to the use of bonemarrow transplantation. The facilities and techniques set up for the leukemia-radiation program were available, and a large number of potential bone-marrow donors were calle'd into'Oak Ridge. Relatives of the Patients were selected, in the belief that they might o 5 e r genetically more suitable marrow. However, with the determination that the doses of radiation were somewhat lower than had been initially found, and after evaluation of the immediate clinical response, it was decided that marrow transplantation would not be The patients showed a typical radiation response, . and during the third and fourth week after radiation had pronounced thrombocytopenia. A i this point a group of blood donors was kept on c a l l SO that fresh blood could be given promptly i f necessary. However, the patients went into a recovery phase spontaneously, and no blood or platelet transfusions were required. Extensive assistance was received from physicians outside the Medical Division in caring for the patients who were subjected to accidental radiation. Shields mission, and Charles 1. Dunham, director of the AEC Division of Biology and Medicine, visited the division shortly after the accident. Special arrangements for provision of tissues for transplantation were made with the help of Charles C. Congdon, Biology Division, Oak Ridge National Laboratory; and Joseph Ferrebee and Don Thomas of the Mary Imogene Bassett Hospital in Cooperstown, New York. Continuing studies on biochemical aspects of the problem have been carried out with the cooperation of Louis H. Hempelmann, of the University of Rochester, and M. C. Goodall of Duke University. Special help on hematologic problems has been given by Eugene P. Cronkite of Brookhaven National Laboratory, and a research program involving the use of tritium-labeled thymidine has been carried out b y Dr. Cronkite, Victor P. Bond, and Ted Fliedner, also of Brookhaven, with the help of Andrew Myron Johnson, medical student on a summer fellowship with the Medical Division, and permanent members of the division staff. Studies on the clotting mechanism and related blood components have been done by Herbert Size, Jacques Gauthier, and John J. Bolger, a l l of Boston City Hospital. George T. Harrell, dean of the College of Medicine, University of Florida, has taken a special interest in the problem, and has arranged for some electrophoretic studies on the serum to be done by sity of Florida, to supplement the extensive studies done b y Granvil C. Kyker's group at the Medical Among the Oak Ridge people who have participated to an exten.sive degree in the management of plant physician; Robert A. Charpie, assistant director, Morgan, director of the ORNL Health Physics Division, and his staff, in a rushed effort to determine the dosage received by the men involved in the accident, carried on an experiment that required many staff members to go without sleep for about forty-eight

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hours.  heinformation they obtained became available promptly enough; to be used as a basis for deciding not to give bone-marrow transplantation to the irradiORINSSpecial Training Division have carried out some special studies on the radioactive products in the urine. ~ 1 1these efforts were in addition to the specific activities of the permanent, resident, technical, and nursing staffs of the Medical Division, almost all of whom have been involved in one way or another in caring for these patients. tained in this report does not extend beyond the period ending June 30, 1958. Because of the nature of the y-12 incident, however, an exception is being made. The five patients under observation and treatment a t the Medical Division were discharged from the hospital on July 30, and subsequently returned to - w o r k at the Y-12 plant. The men will be kept under observation for a considerable period of time, but the observation will be done on an outpatient basis.) Massive Nitrogen Mustard Effects o n Bone Marrow A group of patients i s being treated with large doses of nitrogen mustard with and without efforts at autologous marrow transplantation. An evaluation of hematologic effects of the dose is expected to provideinformation about the success or failure of the marrow The Medical Division is continuing to study the treatment of various hematologic disorders with radioisotopes and chemotherapy. The total-body irradiation program has required the division's taking on a considerable number of patients with acute and subacute leukemia. A number of these are being followed in the hospital and on an outpatient basis. This has required an increased amount of hematologic work and has increased 'the ouipatient load. In general, the totalbody irradiation has been reserved for patients who have previously had an adequate trial of drug therapy. A continued long-range evaluation has been made of intravenous colloidal gold-198 in the treatment of Patients with ovarian carcinoma have been studied with repeated surgical treatment and the use of intraperitoneal colloidal radioisotopes. A limited amount of work has been done with yttrium-90 and lutecium-177. Immediate chemical readions on serous surfaces after intraperitoneal and intrapleural use of the rare-eanc.s. elements have continued to present a problem, there is evidence of good therapeutic effect, at lea<. from the yttrium-90. Intracavitary nitrogen mustard ha: also been studied in a limited number of cases in all( effort to compare its effects with those of the Colloidal Hyperthyroidism, carcinoma of the thyroid, and ' few cases of heart and pulmonary disease have been:a;, treated with radioiodine. The most active research' effort …