Tentative Outline of the Clinton Laboratories Program - Biology Division

Page 1

The zhtachea outline is a tent rti ve one. outline for t%e Louse Genetics grcup (na Bio-orgaic Cheriistry group. group &re now inthe process of being crgzdzec;. stu ting frou the Chas try Sivision. There tre &out six Grkdtic chsrdsts nay wor-ll-ing in tne X research pro grain cytogenetics i s intended to further knowledge of the structure mi function of those entities witbin tiis cell which are the physic tl basis of inherit ace - the chromosoriies mu the genes wkich the] cont an. Since d l mta tic nisa centrL.1 prokien cf genetics. Clifitcn Laborbtories offer iin lrnique upF0rtuni.t; for invest it sting ,mt&ticn problems. rsc i at ions intj; thus be expected aidso of scne oi the i'sctors irivcived in the inter - actions of radiation U-A living utter. The aost z if ect ive &Lents so fard is - There are sever d prokiem uhich a ili be Coiri;iet+i; aurLng ;he next t;;eive 1) The a ' iect of gma - , & dati on ad slow c eu tr ccs ad.t h z rLte of xitos is. 2) The e f f e c t s of different tj.Fes I;f rLciLtict? or, isut,ticn Frcduction in 3)A pre liz i acr j stu q on the genetic function of &dl-bed rzdioisotopes. Three gener.1 ci asses of prot la xiv ill Le unaert;iczn bg this group: 1) A stuay of cte zstkbolism of nucleic sci cs in nor& unu ir ra a i a tea tissues, and in vitro eiq-erimnts OT, the el'fect,, of rz,Ltion on ,so k ted nucleic xius. These exGerbents d?e tesignea tc in a icc t eps sib le

Page 2

iie: Program - Biology Givision 2) Because of the striking sensitivity of bone =row and tast is to ra jih tic n injury, the dte red metabolic states ir,cucea b y such injury of ;rotein iietatolisx, =nd h vol ve a coenzyke, pyridoxine, .uhicn exhibits a marked sensitivity to some form of rodi;tion. For these reasons, ticulcr1;- those h vol ved in assizfdatory functions, : vi11 be investigtited. Tnese tissues will also be bc iud ed in the su cle ic acid studies. 3 ) We intend t c continue a - r lier studies on enzyrre sqste;rs h vol ved h intra ellul ar protein rmtaoolism, i.e. dehydropeptices ,nd peptides with an aide linkage adjacent tothe Fepticie 'ccnu, These sjstem exhibit In all tills -.vork, advsnt:ge will bets ken c;f radio is dope sad st;;ble The propose:: prokxm of the 2saio-3iocheaistr~- grcup i s tc. striag the preparation of radio-active sources re qi ring new techniques, to in vs sti gate the chemistry of new problem stemming from t ne bic logic d + pi ica tic n of radio isotopes, and t o develop precise ad accuraGe lzetkcas of analysis. contaminstion G f various surl'aces ma equipment and the pre part tion 01 pure ceta sources for the irradiation of individual orgzns and animals will be studied. The chemistry 02 ker;lliucl wili be investigated xi th particular reference toits possible toxicity. and their coq on ents will be ueveloped, This iVill involve the use of native, containing a d externally irrzdi;ted nucleic scids. Suethoas for the qu at it at ives epa ation and estimation of nucleic a~~~~ F32

Page 3

Re: Frogram - Biology Civisicn This section, which is oriented towzrd xork of clinical interest,is especially concerned vnth ex per is enid radiation sickness. demonstrated here that the life of an irradiated rit can be saved by parabiosis, and sa intensive investigation of this phenoaenon i s about t o begin. re lrt ing to the ccrllcer problem (radii tion as acase and ics a cure; tte el'fect of cell division on racist ion sensitivity)wiii begin later. The section also &ns t o hold its services ready Tor coUsbor&,ive s f ~ crts. be planed with the rnaudian genetics group, ana * ith r&icchemistry (invention of techniques fc r the aFplication of iocalized sGurces oi ra a ih tion to t ne intern alor k as). In pi irt icd ar, hark will The section can zlso serve fc r clinic d liaison. The work here concerns the preFzrLticn a d naintaining of aninals for tne entire Bio ioa Givision. t h e Louse Genetics group. 1) Tne use of riciio-active c;rbcn in the ; tuq of synthetic Lc t iv it y t o get aore ce ii nite inr'ormticn on ;ne syn t ket i cacti vit j - of inech;nisms with xhich rc dia tic n inter fer s s. This xi li lead to zn invest ig k tion cr' pss i ble 3 ) The efi^ects of radiation on photosynthesis, re spira tic n, etc. 4) The development of a cew assay nethod for the detection of stGble

Page 4

Re: r rog ra - Eiology Livision It i s planned toset up il s u ~ 1 1genetics group x cr king on dr oso ahi h. This organisffi is verq well suited fc r certain tj pas of r baie tion study, eapecid.2.y since it will supply chrorncsomes of a size which cia be reed i ly observed under ti;e t o chrcmsomes unaer the sffecta of z - di ation. It i s here t h & it xi11 be pcs sib ll to & same air ect ly -&at happens I n connection ivith OUT s tudes on the effects cf rada tion, it is neccssdr; t o set up 3sad ; group of physicists whose nain interest lies in devising sFecial It i s absolutely essential to $he ;rcFer fw x tion ing or' the Biology Division LO set up a fei rly corrplete ii tr ary. Ye j re just in the process of uoing Since t h e 3iology Oivision will be located lbout eight miles fromX-10 area, certain administrative fun ct iom will h we to be ilQplicbted at the 3267 buiiaing. it i s planned t o set up an extaneive long-tern; ( t e n years) mouse genetics experiment. The purpose of this eq eri ment is t o determine the inherent cnbnges

Page 5

which ionizing rai iL tion will produce on munalian tissues. tion is being conducted by the &odic Casualty Cod tte e under the a spices of the &omic Energy Commission to deter he the lofig-term genetical effects of the atomic bomb explosions on ma. It aiay take two hundred Zenrs t o get definite in form tion in form tion on maoundian tissues in a Live-to-ten-year period. 3uch an experiment has been recodaended by the ;-.tomic Casualty Cod tte e. of settirg it up. An extensive h vest iga - It m y be possible hy i;roFerly pia me a a x per bents on mice t o bet this i?e are now inths process It i s planned t o take over the organic cherristry grcup from the Chemistry Division ana bcild it up i n our i;bcrztory inthe i2G7 Suilaing. tk is or p nic c'neaistry section xill be tG stwy the xecnu,isrii of orghnic reactions the synthesis of label iec org;nic comFour..ds, t o ;r;ke therii LV: ikbl ? not only for the Biology Division, but &is0 fc ra is tri but ion CI? the ..tcmic Znergy Coinmission of these labelled coq o und s. The function of It i s planned LO dso set up a smli pilct ~ l a tfor the production

Page 11

The atcached cut line is a tentative one. outline for the Louse Genetics group and Bio-organic Chemistry group. groups u e now inthe process of being organized. The Louse Genetics group i s The Bip-orgmic Cheaistrj- group w i l l be t&sn over from There are about six organic cke lists nCi( working inthe The plan is to tru is fer all these men tothe Eiology Ijivision B research prog ruin cj to genetics is incended to further Hcnoiviedge of' the structure a a fun c tim of those s nti ties within the cell which dre the p nys ical Sais of inheritance - the chromosmes ma the genes which they contain. Since d1 genetic vai ation, arid consequently all or,diic &ems m a chroiricscffies, the study of mutation is Bc entr a problem of genetics. covereil for inducing mutations we r;aiZtions. Thus thera air tion fac ili tLs st he to the remarkatle uniformitj cf genetic processes in 611 tjiFes of CrgadS4s, in for nation obtaiced with lormi as ;viael) divergent as .;lolos and dcais almost equ,lsignificclnt i n evalu;iting the genetic effects of radiations in an. from coffiFarative rsdiLticn-genetic studies ,plith aiff e rent organisms a d aif fe rent rdi at ions ma; thus be expect& and also of sori cf the fact crs involved in the mteractions of radiation UP living .matter. Ze sul ts obtained There are several problem which ail1 %e coEFleted uuring the next tx el ve 1) The effect of gamua radicltion and slow neutrons and the rv te of olitosis. 2) The effects of different types of rdia tic n on mt ation production in 3)B preliminirj. stud3 on the genetic function of kbborbad radioisotopes. Three general classes of problem will be unaertaken by tiiis group: 1) stud; of the metabolism of nucleic xias in norul &.a ir ra a i a ted r;echanisics Oi r;lci&icn injury t~ .metic a ate rial in terms of Lte red ;hysicd-chaiiciL proF+rties cf nu chop rote i mad nucleic acius,

Page 12

Trescott Sad age 9/15/47 Re: Frogrm - Biology Division 2) Because of the striking sensitivity of bone narrow ana testis to rada tion injury,the altered metcibclic st zte s induced: by such injury will be studied. of Frotein nietabclisin ail invc.ive a coenzyme, p jr ii ox in e, ;.,hich ex ki bits t r ; Ln sd nation wii l be the first system studied, but other systems, parThese tissues wii lAs0 be incluiied inthe nucleic Lcii stuclies. 3 ) Ye intend to continue earlier studies on enzyme systems involved in intr & ce il ul & rp rote in zetabolisn, i.e. aehyuropptides =na r;e;;tiqes with volved are of funddniental Lrqortance in prc teh metabolisa. &de lix z ge zd jx ent to the ppt i a e bonu. These systems ex nib it 4)A stuay i s being mcie of the ,?~eci?cnis;r.cf the toxicity Gf be ry i liu u to In all tiiis xork, adv a th ge will be tdsen of rai oisc to Fes drid s t - tle The Sroposed progran 02 the I?aaio-Eiocheln;istr; grcug istc ; study the prep amt ion of rhuio-ective scurces requiring new techniquss, to investigate the chemistry of new problems s ted ng from the bic logic d.a ipl ic _ .tion of r & dio isctopes, x.d t o develop precise ana accurate methods of ,nilysis. contamination of vsrious surfaces a de qui penta d the ;repar..tion of pure beta sources for their r sdk tion of individual organs aci animals xi11 be studied. toits possibie tc xi city. The chemistry of beryllium will be investigated with parti cula reference Zethods for the qu at it et ive sep;r.ztion and est i ok tion of nucleic & ids contzining and extern&&* i rrs dia ted nucleic acias. This will involve the use of native, ?j2

Page 13

Re: Frogran - Biology Livision This section, which i s criented towtird work of clinic d interest, is especially concerned with ex per bsn td radiation sickness. denLonstratedhe:-% that the life of *.n ir rz dia ted rat ca be saveu by ,-arabiosis, ana ai intensive invest iga tic n cf tkiis phenomenon is &bout t o begifi. re lL ting to the cm ce rpo bien (rcai&iofi L~ a cause and as L cure; the effect cf cell division on raii ? .tion sensitivity) i-iili. te g in Liter. Tke sect i cn a is c pkn s of techniques for the zpplication of localized sources of radi a tic n to the inLther stu ics The sect i cn can also serve r'or clinical liaison. The -iiGrk here concerns the pre pert tion and maintaining of animals for the entire Biology Civision. t h e Louse Genetics grcup. This group wili work in close cooperation with The following program are under investigLtion at the present time: The use of radio-active cz bonin the study of synthetic activity t o get inore a e finite in fc rm tion on the synthetic dt iv it y Gf iiiechdsms with ,\hich rz di ation interferes. This study i s giarjled i n an attempt This will les d to an invest ig k tion of pos sib h The production cf mutaticns in bacteria md bacteriophage. The effects of rzdiation on photosynthesis, res pir z tic n,atc. The development of a new assay mthod for the cet ect ion of s th ble

Page 14

It i s planned t c set UL asdl .metics grcup working cin drosophila. since it Wili suFF1;. ckfcrxoscmes of i size nriiicn can be resdil; observeo under tke t o C~~CLLOSOIWS under the efieccs of r & a iut ion. It i s here thzt it will be pcjsslble t o okserve air ect ly what inbppens I n ccnnection .Atk wr studies on the effects of mci z tion, it is nec es su y t o set up as mcd gou & of ph gsi cist s vJhose ; kin interest lies in aevisiry. spec id devices for r;e,suring radiation =G t o help u s -,.ittit he G hy sic dh ter preta Lion of It' i s absLlutaiy essenti;l to the proper functicning ci the Sio h gy Gi iriS iO Kl to set up a fair iy complete ii bra ry. ;,e dre just i n tfie proccas of doh & cert s in administrative fur-ctions will htive t o be duplicated ;IL the 9207 Building. It is planed to set UF an extensive long-term (ten years) mouse genetics experiment. The FurI;ose of this experiment isto deternine the inherent cnanges

Page 15

which ionizing rridiztion will proauce on mmalian tissues. tion is being conduccea bq the Aomic Casualty Coitnittee under $he Esuspices oithe Atomic Energy Cods si - nto determine the long-term genetical effects of tne &tomic bomb explosicns on man. It may take trto hundrea j ears to get definite in for nc tion in form tion on umca ~ a ntissues ina five-to-ten-year pricd. Such a n experirnem has been rec wended by the .,tomic Casudtg Committee. of setting it upAn extensive invest ig s - It may be possible by propeily planned ex per bents on mice tc get thi s- . !'"e d e now in tne process It is planned t o take over the org a ic cheniistry group from-.the Ched s try Civision ana build it UPin our Lb orz t cry in the 9207 Suilciing. this organic ched s try section wii l be t o study the mechanism …