Program and Budget Estimate for 1948-49 Health and Biology Project NDP 48C

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REPOSITORY: OFFICE OF HUMAN RADIATION COLLECTION : PLUTONIUM INJECTION INVESTIGATION FOLDER: IRRELEVANT MATERIAL

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HEALTH AID BIOLOGY W vers it y of California Medical School San Francisco, California The project at the University of California Medical School i n Sen Francisco, known as NDP-48C, has been i n existence since the fall over long periods o f time, the changes ofthe blood picture of patients being treated with x-rays tothe whole body. by the staff of the Division of Radiology ofthe University of California Hospital, for therapeutic purposes. fact that they are being so treated to observe the effects of such normal blood so that some knowledge might be obtained regarding what might happen t o noma1 individuals when exposed to radiations. the patients ordinarily treated with total body radiations are suffer - ing from leukemia o r an allied disease and their 'response i s not the It was originally started with the object of observing The treatments a r e given Advantage i s taken of the A n attempt has been made to select patients with relatively In 1946 we were authorized t o extend the program t o include the effects of general body radiations fron radioactive materials within the8me year we were authorized to carry on studies with radioThis work has been done mostly w i t h radiophosphorus. In these results with animal experimentation. General authorization was also given t o check any o f

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The pro j eat ,t present has two sections. %,,ion 1 under Doctor B.V.A. Low-Beer is concerned with the hematological effects of total body irradiation,A) from external sources and B)from internal sources. Section 2 under Doctor Earl R. Miller i s studying the metabolism and A bumnary report was submitted on Novenber 24, 1947 along with A copy of this was the general program ofthe Radiation Laboratory. sent t o Doctor Shields Fur en on December 5, 1947. for the period up to Dec eder 31, 1947 was submitted for circulation within the Atomic Energy Projects in January 1948 (UCRL 41, Feb. 4, be attempted here. treated with x-rays and 19 patients were treated with radiophosphorus and their hematological picture followed for varying periods of time These two reports cover the' field in greater detail than will In summary, we might say that 32 patients were More than94 people have been studied with radioSECTION 1A: The general cm clu s ions to date from the studies made on patients receiving total body irradiation from external sources may be restated as follows: (a) A decrease inthe polynorphonuclear leukocyte count and in the number of lobes of the nuclei per hundred cellr3, follows soon after irradiation with x-rays of qualities used and in the doses given, but these changes do not persist. (b) The lymphocyte count decreases very soon after starting the irradiation, but returns to normal ina few months.

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(0) The monocytes show thc greatest variation in numbers in the peripheral blood, a relatively great increase occurring during the treatment period i n many patients. few months after the irradiation with x-rays, but it disappears later. SECTION 1B: The general cm clu sio as from the studies of patients receiving radioactive phosphorus w e as follows: (a) The total red blood cell co uht ~ ,t o tal white blood cell counts and the hemoglobin concentrations show some transitory flu c tu - ations beyond t h e physiological limits. (b) The platelet counts frequently dropped below the nornal limits, but in every instance returned ta nornal. and much more narkcd than in the patients treated with x-rays. This finding was striking ( 0 ) The prothrombin concentration decreased considerably i n several cases. Such changes wore not observed after irradiation with (d) All the other tests showed no change beyond the physiological SECTION 2: The general conclusions from administration of radio- (a) A method of determining thyroid uptake and urinary excretion of orally administored 1131 has been worked out. (b) The percentage uptake of iodine in t h c gland is indopondant of thc size of the dose. (c) When the metabolism of a patient is high duo t o hyperthyroidism,

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almost all of the administered iodine can b e accounted for by measuring thyroid uptake and urinary excretion. PPhon the metabolism is normal, a variable amount of the administered iadine can not be accounted for by carrying out these ho measurenents. (d) Rough, direct correlations betvecn clinical evidence of activity of the thyroid and of the per cent uptake of the administered iodine have been observed. Attempts at detailed correlation between per cent uptake ofthe iodino with 1) clinical, chemical, and histo - logical evidence of normalcy or disease and 2 ) gland size, have lead t o no useful result to date. and t o t a l doses givcn over many days o f as much as 1 2 mc. tenderness of tho gland, elevation of the sedimentation rate, and increase in the protein bound iodine inthe blood is observed. (g) Preliminary animal experiments with high doses of radioiodine (up to4 mc 1131 per pound of rabbit) have shovrn his to logical evidence of tracheal, kidney and liver damage. (h) Inhomogeneity of the distribution of the iodine in the thyroid and the inability to accurately determine thyroid size in vivo continue tobe stumbling blocks i n determining exactly how much radiation tho thyroid rec eiv gs even though the amount o f radioiodine in tho gland is accurately known. (i) h o cprcinomata of the thyroid in our series have taken up sufficient iodino so that treatmont of the disease is contcmplatod

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'by administration of largo doses o f radio-iodine. of tho thyroid do not tak o up sufficient iodine t o make this approach (3) Moderate Gravest disease i a satisfactorily controllable by the administration of a proper dose of I131. Re diction of there - qui red dose i s not yet pos sib lo from our data. (k) Thyroids showing evidence of thy rod it is have uniformly taken up practically no 1131. , In oarrying out this program and in connection with other routine and research problem in tho Hedical School, numerous house officeks have been brought into contact with the use of radiations and radioactive materials and they aro continuously being trained in the handling of radiations and radioactive material. 2. Program for Fiscal 1948-49 The Effects of Total Body X-rays on the Blobd.SECTION 1A: , In this section we plan to continuc t o follow as many of tho so patients who have been treated in thc past six years as we can persuade t o come baok for further blood studies, The charta and graphs on thcso patients axe being kept continuously up t o date. In addition to treat - ing more patients and following tnc min the same manner astho previous oms, so as to build up our statistics,we plan t o expand our laboratory efforts t o include such studios as that on the grmules ofthe lymphoSECTION 1B: The Effect8 o f Radiations from Internally Deposited

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Radioactive Matorials on t h e Blood, Wo wieh to cmt in ue studying L e blood of as many of the patients treated with s2i n the lest two years as we c m kecp undor observation. Tho series should b o enlarged i n such a way as t o improve our statistical results; It is planned t h a t as othcr radio-isotopcs are found uscful for tr cat m cnt purposes, we may be able t o follow tho effects on the blood of We plan t o oxpand this program considcrably since a new group of poople arcto bo clinically in vc stig at cd insofar as thc ir thyroid functlona (Psychiatry)are anxious t o have the thyroid cli nio of the Univorsity Hospital investigate pati cnt s with anorcxia nervosa and schizophrenia and others who aro apparcntly Mc tion ally normal. uptake, ex crc tion and general distribution of iodine will be studi cd Observation8 on Pooplc Rcceiving Iodinc 131. The Director and Staff of thc Langlcy Porter Clinic using thc radioactive isotope. done on normal individuals, on patients with various statcs o f hypcrand hypothyroidism and on pati cnt s with cancer of the thyroid. chemist is going t o bo rcquircd to help with tho chemical problcms of the sop a ratio q of iodino in thc blood and body fluids. also probably b o roquired i n connoction with thc mcasurcmcnt of the radio - activity of all of thc60 pcoplo. Thrco othcr lino s of ' activity wcro onvisioncd i n 1946 and aabThus we can expand on t h e work previously atra personnel will

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mitted in our projected program for the ncxt four years, 1) the uee of more an hale to cor robe rate thc findings in human beings, study of skin reactions tovar iw s types of radiations and ve stig ation of thc broad field of the cause and cur0 of radiation sickncss. KO havo acquired some new spaca in the aaimal building whorc work can procccd toa moderato dcgrcc and we therefore hopo t o bo able to expand our animal expr im cnt ation. items arc under consideration,but not undcr vcry active prosocution bocauso of lack of spacc and personncl. We havc not cmphasizcd a training prog rm in connection with the and Hospital will not allow us to undcrtakc any large program. mer, it should b c pointod out that WQ arc continuously training from 6to9 young doctors i n radiology and their training involves a knowledge of radioactive mtc rials as wcll as thc use of other radiations. Othor Staff mcmbcrs and Resident Physicians arc using radioactive radiation therapeutic dcpartmcnt to de non strat c to trainees in othcr parts of tbc Univursity what happcns to patients being irradiated. Wo fro qu cnt ly havc poop lor c ferr cd to us with radiation burns o f long standing and thcse can also be used for dcmonstration purposcs. cannot howevcr, undertako any largo 'scalo training program until such tho as wc havc a ncw building with adcquato space for a training staff and for student laboratories. W e arc willing to use our facilities which include the

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Tho budget for M)P-48-C as submitted i n prcvious years has not uonnel and fac il it ios havc bocn uscd without proper or oven in dome cascs, any rcmuncration eixhcr to thc individual sort otho Univcrsity. Tho budget submittcd below attompts to corr cc t the so inequities. should bo pointed out that while wo do not have a large amount o f space in any one place for this program, it is being carri cd. out in many amas by coopcrativc effort. Thc clinical fac ili tics of tho hospital and Outpatient Department aro utilized for obtaining and observing patio nts. Thc Thyroid Clinic group uses thc ir spaco for studying the arthritics, on many o f whom the blood pic tur c is followed. The pathological work i s dono in thc routine patholoGica1 laboratory. Some laboratory. Iodinc tcsts arc donc inthe iodinc laboratory and it i s Lenglcy Porter Clinic wc can have spaco fora biochemist t o work on problcms associated with our projcct. Doctor Milier s quarter saro usod for measurcacnt of radioactive iodino In t h c Radiology Division on both hospitalized and ambulatory pati cnt a, Ye havo our own laborntory for hematological work. Ve uso our physicists quarters for various purposcs and tho on t irc Radiation Therapy Dcpartmcnt i s used for adminiatcring x-ray and radio act iv c matorials and for observing the pationts. A new laboratory for clinical in vc stig ation with radio act iv cma to rials

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is boing installed by thc Univcrsity i n conncction with the wards of tho Laboratory f o r Expcrincntal Oncology. available for radiation physics in thc Division o f Radiology. More spacc i s soon t o 'bo Spacc in which project cmployoes will work fill time - 496 Spaco where pati cnt s will be seen, sc lect cd and Tho incrcase inthc "payroll" portion of thc bud@ i s duc t o tho following factors : More adcquatc rcimburscmcnt of the University pathologist etc. ; incrcascd salary for a full timc physician assistant ; more physicists for major problcms, instrument opcration and health assistants for clcaning glassware etc. ; afull timc secretary ; and a Gonoral Assistance Fund for part tim c services of an animal car cta kcr Expcnsc and Zquipmcnt : For the incrcascd hclp wc wili nccd incrcascd fac ili tics. Tho laboratory apparatus, prot cc t ivo mcasurcs ctc. , ncod improvcncnt. Tho soc rct ary has uscd Hospital cquipmcnt. Morc animals will bc

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Frobab le Distribution: In Charge : R. S. Stone 25% of timc about Aasiatant Physician up to 1 Physicist part or full timo up to 2 Sonior Lab. Tochnicians (Hornet.) 1 Scnior Pathology Tcchnician 1 Biochemist ' up to Consulting Phy sicians Ekpcnsc and Equipmcnt Laboratery cquipmcnt, supplics and alterations Animals and animal car0 Offico cquipmont, supplics and cxpcnsc. Purchaso of various tcsts otc. Un all oc at od