Long-Range Program Volume II Appendices - February 1959

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Int r oduc tit Jn This second Volume of the Labor < ttory ' s Long Range Program contains appendicc.: which give detailed information 0 1 1 the p r o g r a m of the Laboratory fro ' , the standpoint of 11 c component organizations: pared by the divisi(,i .ind departments c 01 erned ; they 1ave been reviewed and modified sonif N ticit from the over -a1 Laboratory tandpoint and edited to givtx ac 111 t consistcncy c~~ >,< t.med essenti,il to the o v e r - a l l that these apperidic I be as spontaneous d n vxpressic).i of opinion as possible, compltltc onsistency of f(9rni t:,d compatabi ityof content being of sec ondar) ! I > jortanct The scitJtitif. ,rrid technical d i \ is i Iris we rc reyut sted to prepare i ties and needs and of the Labordtoi , five to ten years, ' * ( cjgnizing that m,injct the detail so programs and even prograrns their ,(*Iveswill h a \ e char qed or vanish( d when the next review is made.I)( - ~ , i ~ et his unavoidabl) tentative qua ity, 11 is believed that a present at ~ o r ~ They must be read ~ i t hfull understandink oi their pro \ sional character. 111 almost every c.1 - 8 these appendices v ('re distilled from much more detailed suggest i ori -tipplied by r - nc ni be3 of the staf of the division seen today ha\Te bc c ~ ~ in it te do r are press nted i n high11 abbr v via ted form It 1s believed, howe ei, that what icp rest nted here doe, give a reason - ably representatixrc I C ' W of the types of pi ogram s whicl the Laboratory will be engaged in ftr the next five to ttL near s and of t le sut)port which place in its Ii rog r till. They w c ' ( ' encouraged t o I ould be in desc rib lng their pro qr ams for the next Ii fl is vcin is the oril) possible way to present an over -

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1. SCIET4TIFIC AND TECHNICAL OBJECTIVES Biological work in the Laboratory was established originally because it was clear that t$e ~ ti liza tio nof radiations and radioactivity would soon run far ahead of oiir Z nowledge of their hazards. was then. There is < i the toxicity and hazards of radiations the Laboratory and i t > unique facilities pro'. ide a climate which is part ic - ul a rly well suited fol toxicity. It is necess'iry not only t o consider the effects ofa wide variety of radioactive agents large populations ot experiment a animals, but also to relate such injorriiation to man, whir h in itself raises formidable question of interspec i t . : relationships Although the print ipal objectives of the Division a r e o r c iited to practic,Ll rriatters of radiation toxicity, the scope of the progl-ani i - necessarily broad, since radiation has its effects This is ,is true today as it oritinuing need to learn as much as possible about The \ )road base of the program of t3valuation of the many vexing prolilems of radiation ( !c'ncies iri our know edge of basic phenomena. Earlier siudic~, 111 the Division corlt ributed in am,iJ or degree toward area,many of thc prt.sc.ntly applied indiistl lai permissible amounts of of direct experinieril,iI Mark in the Dix~isioii likely that the niort. ; ( ent findings in reg,ird to retention i n t h e body of alkaline earths (SUC: 1a i strontium,bari uni. and calcium I and the relative toxicities of alpha , i r i c I beta ray5 will result in significanl modification of levels a r e probahlv onservatirre At the present tirne, it appears fortunately in a di r13(t ion indicatinl that present For the futurv it is certain that it will be nec ess iry to determine on very large pop uli tian s the effect,or lal k of percepti1,le effect, of small amounts of raciioactivity con5iderc.c as safe for tf e industrial popumounting levels of aide spread hum;rrL rad oactivity fron weapon tests and from the rather large - scale geographical distribution 01measurable radioactivity from the Win(lsca1e mishap in En :land. The imrrletl < % c ) 'of the need f o r till., is obvious f i om the gradually

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amount of radiation, and the nature ctt the aging process itself which some way f)r(ailisl’oses to cancer 3 ;rciiated tissue whit hfend toward c < Incer ,the conditioiis of less likely tl result from a given Work oil these aspects of the problem has I<roceededmainly within the rather broad scope of the basic research prog iam s in the Division. Changes in the fine structure of cells are under constant investigation using the elect 1’011 microscope and other modern ttrols of cytology. esses of giowtli rn relation to cancer formation an‘l the spatial distributlon of radiatioii i r relation to cancer art being studied i n both basic and that produc etnn ~c r have been studit d,in one cast by pathologists i n the’ Division, anti i n dnother case by dir(bct collaboration with a university group inter-es tbci in carcinogenic c o - factors suck experiments as these contribute to i n understanding of ba-.ic problems in biology and, in addition, they toiir of srriall ainor,ilt c of radiation The effects of combining radiation with chemical agents major part of the rlational effort to determine the toxicity Thes gnificance of the aging process, and its relation to the forma - tion o f canceI I S one in which the D-vision pioneei ed and h a s continually trying to intt>r pret data which were originally devl.loped over the last and showed, u:iexpectedly, that the iiiean life span of animal sir rad lat ed at low levels ac tiially exceeds that of iinirradiated a iimals While t h i s ha5 been verified here and elsewhere ,I number of tin es,it requires further study In par ? ICu lar, it must be rel < ite dto basic I’hysioiogic and pathologic process e5 111 ~ ~ m em anner not knoxcn at present1,ut which may becorne evident i n si1 j5equent studies Until a half dozen years ago this type of study was beirip pursued almost ent Are l ywithin thts Division. ever, many it. ,.castigators both in this country and abroad are concerned with this iubI + ’ C t and are cooperatirlg in the study of this problem. ‘The acquisition t ~ f two gamma-ray animal exposure r )oms by this Laborntory has greatly i r I-r-cAasedthe scope o t this work Otir approach started <is the ma them at.ca1 one of verifying and The fii st definitive c xperirnental studies were tnuther laboratory witti the substant a1 support of this Ihvision The intcArest stimulated i n ttus area by OL r earlier work has r e - sulted in mdiv fruitful collaborativ(>s tu dies on the Wr st iv,ocisti s at present collaborating wit1 us in the study ol thta histocheniic .Ind physiological r e ilts of ir radi Fting their stock 0: A niiir b6.r of investigations of large human populations has been undcrtakthn 1 ricli’r the direct programs of this Di- ision, in close co1,abor-

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amounts of radiation might ii cancer,a program was iriitiated to investigate ihe incidence I f bone tJ mors in relation to natur‘ti !cxvels of radium in Iiuman beings. tult of the original backgroi.nd radiation survey that was carried out a t the time the new Labor at orb site was chosen,itW ~ Sfound that ihe deepwell water supply i n thi>, \ i ( inity had a n unusually high radium i ontent. Subsequently, it was discovi,rtxd that local water supplies in s e \ era1 mid - western states also have zl very high radium content. lluman population served 111~iliese water supplies was initiated nan effort IO determine the true incideric e of bone tumors, Lsing as controls persons ,ittributable to the higher r < id,u mcontent of the water has been detected. 4 study of this sort encount ( > r 5c ert a in basic proLlems as fore xample he accuracy of diagnosis 11 different geographlc j1areas, the pdssible Tistory of medical injectio 1 - of radium and occul)ational exposi re, arid the number of cases which rnight be attributed to elevated leve s of ilu - importance and can be it tah t * t l only through an expansion of t h ’ .present >rr)duces mall but abs ilutely importaintinc r eases A survey of the T tiu> far, no difference in bone tumor incidence These problerrLE are obviousl: of critical Studies of large po ~ i : ~ ition sof irradiated animals have not been carried out up to the presviit time although i t nou appears that they will be necessary if we are to ,it( rnpt to answer certain questions the possible effects on l a t - g t h human populations tsxposed to 1 0 s level:; of mentation and so forot)v ~ c ~ Is social reasoiis this question w111 have to be studied on the basis of risk 5 Llready being incur redat various p1acc.s. Although such work 1s bel i L ; tsxpanded, the use 0’ experimental animals would permit closer cont rt a prohibitively large niinib( I of small animals v..luld be requii e d to detect the cancer response to ar riGi u ; i t sof radiation coniparablc to thi natural background, it is still l,osh,t110 to design ex;icrirrierits which will at some - what higher levels, deterir 11,c whether the response is or isn )t truly Proportional to dose W(, ria suggesting, tent at \rely, that wit1 a colony of ~ ~ ~ ,oo om ice it might b f JJoSSlble to de term i rie the general rules r e - lating dose to probabilit) of Ian cer, and perha]’: to infer iron this what some general ground iule v.-hich would g11e ci tjetter picture Than ii: available from presenl sktlciLIations and froni the few past exlleriments that are available f o r stIiti\ ,ind evaluatiorl. The anthropolop c.il milieu is not subject to control ed ex peri - over the variables to be encounte I ed While Such a program, vhich would

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showed that anin2i.s treated with Sra9 (:odd endure a Irluch larger dose c f radiation than thcLe given an equivalent dose of bone in arrow irradiation forming function:, of the bone marrow had been taken aver by the spleen which, being re riot e from bone, had received only nominal amounts of irradiation 'This resulted in a n investigation of the possibility that the spleen might ( oritain protective principles.Furt lier work carried out under a colla borat i \ e project, showed that bone mario w itself, as might have been SUS ~ E (t ed, was protective.This disco v cry, made under a programmatic s:iidy designed for othisr purposes, has resulted in the most favorable <ipproach to treat men ' of acutc radiation sickness ncw known This is now being studied actively in man J laboratories and Carefii study of these anirria!s revealed th it some of the bloodAsa resi,lt of our basic biochemical studies of thc effect of racliation on enzyines Lt u(i5 suggested that cert ci in normally clccurring reducing subs t a n c e s might bc important in determlrling the inten \ity of the radiation response It wzti indeed found that thf injection of c t.rtain natural reducing substances JUSt b)t,fore exposure great i y mitigated tlie effect of the radiation. The imp lica ti or - of this were firmly the Dir ~ sio na m stablished in i series of studies in stimulated intc,nsi\ (1 investigation tls e where Certain <Lrcdslikely to be corn < ,m ore active deserve special mention plant sciences c.nierging from the biosynthesis prok ram reactor, now u il ci chr construction, will within the nebLttwo years begin to provide inforrr,Ation about the effects of high and low dose rates of fission neutrons,which so far represent a scbrious gap in(Jur practical knowledge. Epidemiologici! studies w i l l be expanded, includin,; radiLumeffects on bone tumors and leiikrmia a s well as further exploratioils i n human genetics Acquisition of r,ew dog quarters will make it possi1)le t o study the effects of about tell f i - ii on products, hitherto studied only in mice and rats, which are potentially 01 importance in the t'vent of reactor accidents. i s under pre lint in ary design. For thr immediate Ji ture it is proposed that a substantial i,crease in small animal quarters w 11 enable u s to explore the unknown qi'eztions, soluble only gith the use e large numbers of individuals, rtblatiiiC; to the probable efftactiveness of : mall radiation d o s e s :n producing per ei,tible human damage. A separ'irc appendix to this re.)ort will deal .vith potentialities in the 11 is nr t proposed that all c)f the basic biol ,gical programs be expanded to the .;ime extent. On the other hand, i t uould seem that in sorne of these area - w e have not been d:, ictive as curl ent problems would rf'- ItLS proposed to place mort emphasis on cancer and human ger,etics which should be brought

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programmatic studies of certJ 111 practical problem,. in toxicity of radiation with the maintenance of a t>ro,ad;y based group of biological speci, lists in all fields of life science, who,-(, .I om mon interest in radiation is rexinforced by the close collaboration of .-,fiysical scientists and of the va riou.service groups within the Laboratory specific problem may seek a l\.i(-e from persons with a clear undfhrstanding of the implications of the Gar-iotLs areas of basic biology in relatic n to his particular problem, while the :ri;m studying a partic u lar basic problem is kegt aware of its pos s ~ b l ep r ~ it I ( a1 implications in the general ai e a of The Division possessi ' i rather large collection of speci,il equipmc:nt and facilities for biologic a1 research which are more or less peculiar to the radiation field problems in biology, major pti ys ical equipment is 5 0 far of less In port ance here than i n the physical ,ind On the other hand, the portance to university scienti ,tL in the area and,fcir that matter coast to coast. bcth in this country and abro<f\i<indh ave been utili;,ed by many ingest i gators fr3m university and go\rer nir I 111 laboratories for tlf(, solution of i rob l cms which could not otherwixt h I a t,t.en investigated A s wil! be discussed in the context of …