c' OPERATION CASTLE - FINAL R@ ORT PXOJECT La

Study of Response of Human Beln~sAccidentallg Exposed to SigpLflcant Fallout Radiatfon '

Naval Medical Researoh Institute Bethe&, yarglaad ana U. S. Baorrl Radiological Defense IeboretOrg San Ranoisco, California

I-

October 19%

1 J Follmiag the detonation of a thennonuclear device on Bikini Atoll on Xmch 1, 1954, 28 Ameriaans and 239 Marsballeae were exposed to fd,I- out. One hundred flfty-smn of the Marshallese were on UtlrU: Atoll,

6.5 6.5 ‘681~on Rongelap Atoll, end 18 were on the nelghborlng atoll of Mlbgnes. The 28 Bmericana wem on Rongerik Atoll. The premnoe 02 sigallicant fallout on these atolls was first determinsd by a recorw dosimter located on Rongerik, when thls device went off scale at 100 NFi per hour shortly after the detonation. Emergoncy surveys of redie- I tion were detected upon the lahabited atolls, and evacuation of inha51- tants to the Naval Station at Kwajaleln was promptly carried out. Thc dose of radiation to which the individuals were exposed am celoulated fro31 the inLensities founc! on the islands and the decay exponent of fallout metoriel. The 5n~ividu~1I.6on Rongelap received approxbately 175 r, those en -nee reoeived approximately 69 r, and the Americ&s on Rorgerik receimd an average cs3culafed does of 78 r. Tbe Marehallesp, on Utlrik reoeived approximstely U re Tbe fallout on Rongelap, w~

nqrrnd to E lesser eatent on Rongerik was &tinct;ty vlslble. No fallout was obsemd on U-ik. A slgnifietmt nmbe of indivfduaLs on

Rougelap suffered from mild nauaea and one or tmo Mivldu8ls dted on the day of the 5xposurc. With the exception of 1iaua8a &I om Ai--, nae individuals hero were no other definite gestrointsstlnel symptom in the other mrshalleae or ths Americans. The Karshal.lese on Rongelap and Ailiagaes, and the Bmerlcans experienced to a varyhg degree burn-,

ku; of the eyes and itchhg of the ski0 for I to 3 -6. LBfer sign0

iI I 2 i, 0 of rsafaticn LJury 5acluded definite epilation in the Rongelap and AUingnae group6,and the dwelopwnt of spotty, maperfieid, hypr- pigmented akin lesions that bequamatad from the tantar of lesions outwards. some caws fhs skin damage was sufficient to result In raw, weeping leeions. There was no full fhlcknesa necrosis of the skin. The dmericans developed only minor skia lesions without ulceration. There were no &in lesions in tbe utirik natims. dll lesions baled rapidly with no lurthsr breakdom of the akin noted during the period of observation. Mioroecopic araminstion or bfopsiea of the le6iom showed chsllgsa usuLUy aawciated with radiation injury. Fully clothed Individual8 and those remabhg inside of baildings or huts were protected to vmdegrees fhmdevelopient of lesiom. Aematalogla changes were dafinite In the Rongelap, Wiagnas, and the Bmerican groups. Igmphopenla appeared promptly and was peroiatent for a plonged period of tima. Neutropenia occurred in all of the individuals with initial minimrrm oaluea occurring around tbe llth day folloued by IUI Incream in tke counts and a secondary nlnlmrn around the 40th to 45th dny. The most consistent hfnnatologlc chtup (1s8 the dqtression in the platelet counts. Platelets were below normal when first counted on the loth day post expoem and progressiwly decreased attaining a minimrmn between the 25th aud 30th dq. Although recowry commenced follmw this minima, the platelet counts had not returned to normal by the campleaor. of the Initial study on the 76th poet sxposure day. The lncideece of vario-a respiratory and cuQneous Weations waa Identical In all exposure groups and bore no relafionship to the hemafologic chatpa. This report la one of the mpurts pressntfng the resulta of the 34 projecte partlaipating in tbs WUtery Eifets Prog~amof Opsratfcn Castle, which included ek teat dsfo~tlona. For readers Interested in other pertinent bat iaformstion, reference le made to fiR-934. SRILVlRP OF WFMONS EFFECTS TESTS, MWtarJr Effects Progrm. This aummacy report includee tb following infornStion of possible germel interest.

(a) An ov8r-sll description of each detonation, including yield, height of burst, ground zero loaatloa, time of detonation, ambient atmospheric conditions at detonation time, etc., for the 3 shots. (b) Discuealon of all project resulfs. (e) A swmary of each project, Including objectioes and resulte. (d) A omplete listing of ell &ports covering ths Military Effects Teat Program.

4 Operation Caetb did aot ineltda e blamedlcal pxqpsm. Tim patticlpanta in project 4.1 were drsnn from various laboratories and were totid& ~pwparedfor a field progrerm when the Commder,

JOhF Teek ForOe 7, tpgBL.tJy mlSSted thaf a jObt DOD-ABC Ikdlcal Research Team be orgded. Dr. John C. Bugher, DImetor;Dlvieion of Bhl.0~aad Medicine, m, and Lt. Col. Browahg, W,, EA, Surgeon of the Anned Force6 Speclel meapons Project, selected the Projeot officer end requssted that the selection of t6-a aad professional paomel be oommenced hmsdlately. Tbe cwperation of ths Surgeons General of tb -8 -0 and Ah POTOOWEB &LlCltad. Ft~mAdmiral Cla~eme Brown, DepUts Swpon PenerelD Medical Depertwnt, U.S. Navy, gam haedfate and complete support of all ndmedical research tletlvIt,i.es and assigned responsibility ta Capt. Van Tipton, E, En, and Commander Rarrg Etter, MC, El?,of the Atomic Defense Divlslon, Burerru of Uedicfne end Sllrgary’, Navy Department, for the implemente- tion of the project, Since little detailed information %as wailable about dose and initial spptamatology, the research tea waa organized to Inc1ud.e the fol3arring talents for the constitution of the aaergencg medical teems infernal mdlcjne, hematology, radiation tschmhgy end radio- biology. & ttse selecfion of prsonnel the emphasis WM placed on pest ezperience in biomedical zwmarch in the fhld with atonic weapons. In eddition, ~OP~E~OMwere defor e second echelon of

5 ...... ,. ..

additional epsolalized par8onnel in cam they were needed. Accord- Ingly, a preventips medicine unit of the Camander-in-CNef, Peclfic Fht, wa8 alerted for possible Luxteriologla studies; blwd bank personnel, aud edditlonal ollnioiene and 11m-6 were notified in

0868 oonditiona justlfbd their semices in the Kaajjalsb Rear

AdnirSl BeWWHogan, WBC,161Jp PaCUiC Fleet MdiCa OffbX', imrmsdiately made needed medical feelllties of the Prlfic Flset

tlV€iilEble.

Personael were obtained within Continental Mtaof the U. S. for the research tern as follonsr

Napel Medlcal Ressarch Instftub 4 medical offioetr, (E. P. Cronldta, R. A. Conard, N. R. shulman, and R. S. Fm) 2 medical servioe coqm off%cere(W. B. Chaprum and Re Sharp) 6 enlisted mea (C. R. Sip, P. X, Schork, C. P. A. Sfrome 1. C. clutter, R. E. well, J. s. mf U. S. Navd Radiologioal Wenee Laboratorg 1 citrllian M.D. (V. P. Bond) 1 msdical B0rvIceJ 0orpE officer (L. d. smith] 4 enlisbd men (m. H. Gibba, J. C. Hendrie, 8. S. Aqpma, J. (n) Flarregen)

Division of Biology E& Medicine, AEC

2 civfllan M.D.88 (C, L. Dunham and G. V. leRog) Amd Forces Special. Weapons Project 1 Amy Medical Offioer (L. E. BrmArUg) Preliminary studies had been made by Commander V. S. Hall, ICa IRR, Station mdedioal Mficer and his staff, and decontaminat%on of 6 ~ ..,...... ,

the. individuals was well rmderwey when Project 4.1 personnel arrived ia tho field. Preliminary henatolcgic studies indicated that the lndiriduals probably had not received acutely fatal doses of radiation. The prhery reaponsibiritlea wifhin the project group were delegated as follans:

Clinical obse~tio~and C- - Lto Ne R. Shulmaop E, BN Orgenization and operation of' laboratoq - Lt. R. S. Farr, W, l!SU Conpilation aad daUy analysis of all data - Dr. V. P. Bond Decontenination end radiation meaeurement - Lt.(jg) R. Sharps MSC, llsll Senior Petty Officer in charge of l.8Lm-atorg - P. K. Schork, mc, EN As *.e clinical picture developed, e further breakdown in responsibility

=a6 necessary. Commander R. A. Conard, GC, USrT, vas made r96pot181ble for a alp m3of skin lesions, and Dr. S. H. Cobn om mado respozr slble for studying the problem concerned with the excretion of redia-

isotopes and the estimates of body burdens in the Earposed individu&b The project officer conmcends all of the professional and technical members of the group for tbah wellent motivation, inltiatioe, and voluntary long hours of extra work that mere essential for the secmplisbent of the clinical and research o5joctiws, and for the r4;iid completion of the prelininary reprt in the field. It is amphasized that the work ~~118a cooperative endeavor in rhich all viere mutually dependent upon each o*r. The MUlng offort6 of ell con- cerned constituted a renarkable exemple of tefun-mork and sacrifice of

7 personal mbltlons and desires for tb good of the project at large.

The authors nish to expmss their gratitude and indebtedness C, Dr. John C. Bugher, Cspt. Pan Tipton, and Coamarrdsr Hamy Etter; Capt.

Ra E. K~ll~n,LE, EN, rusd Cwte T. L. RiUmOn, C- end Exeoutlve Officere, respectiwly, tsaoal l7edioal Research Institute; Cqt. R. A. Hinaers, UNS, Directar, 0. S. Naval Radiological Defense Lab~ratory, end CBpt. A. R. Bahnk%, KC, Usli, Assodate Diwofar,

USfiiMRDL; all of whom gem udumited Bupport and reduced administratim p-ocedures to a bare mlnlmm, thus makiry It possible SOP the mzlt to be assembled and undernay in a matter of hma. opoa arrival et Kwajalein Rear Bdmiral R. S. Clarke, UIUS, Comaad- lng Officer, U. S, Naval Station, KwaJslein, supparted Project 4.1 nlth

all the feelllties at his dlsporral. As E result, a laboratorg and clinic mas established and operating within 24 hours after &vel of the project persannel. Project personnel also wish to acknonledge the outstanding con-

tributions of Col. C. S. llanpln, IC, USA, Field Cmumd, AFSFlp, Cape, 8. A, H-ht, tlc, Eii, Division of ITlitary Application, AEC; Col. iC, Houghton, LE, USAF, Special 17eapona Center; Copt. Donald Demnt, IC9 W!?, CEGPAC Fleet.; Dre, T. L. Shipman, T. mhlte, and P. Harris of LESLx Dr. GorBan Dunning, Divlslon of Biology and Kedicim, AI%, and Dr. Go V, SmFby, University of Chiaago. During all phases of the

early cam? of the axposed indlvldds the foregolng particlFat%d 88 much as thelr other primary duties would psnnit. In addition ve nisb

8 to tha& tbem for the extensive and complete data whlch they collected in the atolb or their hame laboratories and kindly fipmished to the project personnel. The continuow help and aoopration of hvst Terrifary wprc eentatives, and their aid in obtaMng neaessary contra1 data on native Marshallese at U4m0, is hereby seknonledged. Fle wish in parflcular to aaknmledge our krdebta8ness to blr. John Tobin. Hls help as an interpreter, and ME extensive knowledge of the Marshalleee langusge and habfts were inpsluable. Lt. J. S. Thompson, NCs ENs furnished his records on the exposed individuals WonfaPinatsd by the radiation group of the VP-29 squadron stationed at Kwahalaino The authors wish especially fo express their addratdon ?or the excallent job done by ths medical pertwnnel of the U. S. Naval Dispsn- aary, Knajaleln, in completing the axtenslm laboratory exmiinations fhEt mere required to obtsin a prompt initial evaluation of the severity of the radiation injury. The authors are heply grateful to Dr. David A. Wood of the

Uniwrslty of California Hoqitel, Sea Francisco and Dr- Edward 1, dlpen and Ellss Pat Roau of the Naval Rediological Defense LaboratcnY, Sari Francisco for pvizluable aid in carrging out the histapafholc@mLl evehation of skin lesions. The extensive contributions of r&* C. A. Sondhsus of the USW.DL in dosage caloulatlons we grate- e&ntn?= ledgedo

9 1.1 Objectives...... 17 1.2 General Deaarlption of the Erpoed Croup ...... 17 1.3 Epaolation ard Early hof the Exposed Oroaps . . 18 I.& Estimation of Maole Body Erternal Does ...... 18 1.5 b-te of hkixlud skln Dose ftom the around ..... Y

CBapTw 2 CLINICAL OBSERVATIONS AND TKERAPX . . e 39

2.1 Introduatlon...... 39 2.2 Gyrpptoma and Sdgm Related to Radiation InJw .... 4~ J 2.3 Cynical Observation ad lbelapy a8 Related b 41 H~t010a;iealMndingS. e m +a . . . . 2.4 Be Effect of an Epidemic of Upper Respiratory Infeation on an Irradiated Population ...... 45 2.5 Cm@son dth the Utirik Omup of Diseases Seen in the R@ngehpand Ailingnae Groups Mng the Period of Observation ...... 47 2.6 Changes in Tielght 88 atl Isx3ioation of M~turbanoefn t?m Operellfdetabollem...... 48 2.7 Ihe Effects of Pmgnarq ...... L8 2.8 Discussion on the Use of Bntibioucs In this Gmup and in Radiation Injuqv...... 49 10 3.1 Introduotlon * Ear4 ~t€4mtolcgyRofmabl.0 to tim Sldn ...... 65 3.2 SMn Lesions ...... 61 3.3 Epilation ...... '72 3.4 NsirPigme.nt.tion ...... 73 3e5 Faofor8 Influem & Senmi* of skin Isah.... -21 306 C~l8tiondtb EexEatolCgioal ...... 76 307 M..~ion ...... 7? 3.8 cOWhl&OM ...... 8.5 c- c- 4 xmAToIax ...... 93

11 . 501 IntrodWtione...... 1.6? 5.2 P&slcal Environment Studiea ...... ].aj 5.3 BnimelStudLea ...... 16:. 50b Imlmnstudies ...... 16;: 5,5 MsGussion ...... ].& 5.6 Conclusion ...... 162;

RECOl.&EIH)ATDS!IS ...... JLL~!EtATIOraS Paago Fig. 1.1 Ihe Uyhg Area on Rangelap Islaad,Mioattqg the wt, open-~~rc~nstruo~...... ?:: Fig, 1.2 Ustagrsm of Pmportion of Total Dose Contributed by Various Enera Regions fTom the Fallout Radiation . x, Flg. 1.3 ,Clmmilative Dose m a ktionof Tipro diter the z' Dotanation...... Fig, 1-4 Comperauve Dapth Dosea for Bilateral Expoaura hpm a small Soume Multiple Soume 4 I? mVlVTithcObslf@ . e osa. 34 Fige 1.5 Comparative Depth Dosea in a Phantom lEan of Initidl Atomio Bomb RBdiation sad Radiation Rpm a Field of Fission Products...... 3e Fig, 2.1 'Lhe Blood Count Chengeg in a h.0 Year Old Child dth a Febrile Illmas...... 9 Mg, 2.2 '&e Blood Count Chaagwr in a Wty Pear Old pbpa dth a Febrile Illneso ...... 9 Fig. 3.1 Coqnrieon of the Incl&mae aad of AppeaTame of EpUeUon Spd Neek Lesion8 in the Rougelap and Ailinp3eOPOUP(I...... **..oo.... 5'1 Platas 3.1 to 3.24 Color P&*. bgeds to be S~ppUd Fig. 4.1 Serisl Changes in Neutro@~ile Counts of Roslgap 0- For nose Loss 5 Ieara anl Greater than 5 YseFe of Age...... 139 m. b02 serial Chflngw in xgJl@oc* count of Aongehp Group For lhose Imsa than 5 l[earo ana Graafar than 5 xsaFoof&e~...... 141 Fig. 4.3 Ccu5~tlveserial changer3 in the motell Lsukoogfs, Neufrophile, srd Q@mcyte Counts in fhoee Gwatar fhur 3 Yeam Old, Rwgehp Group * e e . . . e . a . 143 rigc.4-4 serial Platelet Cbenges in !hose Less than 15 Teers and Greater than 15 Yesrs of age of fbe Rongelap Gro~pe e o a e o e o 0 t o e 115

Fig. 4.5 Serial Totel Leukocyte, Neutrophile, arr3 Count in Expose3 pmerioana ...... ~7 13 Figa..4.7 Serial Esoinophile Counts on Those Less than end Greeter than 5 Years of Age of the Rongehp Groxp...... 2.52

Figg.433 Serial Hematocrits for All msedGroups . . e . :<53 Fige &? Cumulative Neutrophile Counts for the Rongelap, AiUngnae and tTlajum Groups at the Tine of Pa& Depression...... z.55 ?!.go 4JO Cmulatiw Lymphocyte Counts for the Rowelap, Wllngnae and ?iajrw Groups at the Time of re& Dopseseion ...... :.5n Fig, Cmdative Platelet Counts for the Rongalap, Ailfagnes, Utirik and Mejllro Groups 8% tke T~XEof peak ~ep~eeeion. . . e . . e . e . 159 F*o 501 Well, Rowel+ ...... :?& F5-g. 5.2 Cistern, Rongelnp ...... 35 F:.ga 5-5 Autornciiograph of Rosgalap chtclen tlksa, 1%; X, 21 hrse expocnrre. Bahd secrfliced 45 dsy8 post eqmslrre (Argonne 1lational Laboratm). e e e . 0 1% Fig? 5.4 Autor&o,-raph of Xongelap p4g tibia, 42 hrsD exposure, Aninal saerlficed 58 dsya pcst eq.mm% (UXRDL)...... 1,I. 2-2

2 2.

205 3.L 302 16 17 ... .

: I

I I ” I 20 I 22

, deposits of fallout materid on the boas dace itself. Ths latter ia 5qmesible to estimate, but tbe fona nqy ba rolrghly ettmptdd as sollowe. The beta dose rate in air at ab- of three feet abow ths smface of an infinite plane cantsminated with mixed 24 horn old fission pl’bducts 58 estimated fo be abouf three tM8 ths gamma dose. The nidlhe gamm dose is 8ppodmaW.y 60 per mn-2 of tbs portion of the air gemns dose due to 80 KV radiation ar abm. Tkie portion in turn is estimated to be 90 p~zaent of the gamna dom measured in air by tbs lmtrment. Thus the dose nt the nurStlFe of a phantom -sed to mlxed fisslon pr-t radiation from an e@. lane ~curcewht be qtedto be 3/(0.6)(0.9) or about 6 tines the rnldllne dose, if both occur at three feet off the p2pund Such a depth dose measurement ha6 in fact bean made experimentally at a preoioucr field test,* using a phtm man tapoeed to bath the 3dtiG. end residual r&tfon. The depth doses for each situation are ah- in Ffg 1.5, with all data 8s per cent of the 3 centineter dose. With the &verging initial rdation tkm tbe point of explosion, the exit dose was seen to be 63 per cent of the 3 cm dose, but with ths dlffnm rssitfual field of fission produat radiation, a &ace dose 8om~8 tirms greater thm the 3 cm and deeper dose from the harder gmnm components waa obsarvmd, This is seen to be or the 8- order of magnitude as that estinafed above, At heights abm and hlm the

3 foot lml this surface dose would becone 1Opm and higher respec+

* F. R. Chgnbers et til UnpUbJlahed data from Operatior Upshot,/ KKlOthOb 25 .

ively, but probably would not exoeed 50 thee tho 3 foot air gamma dose or 80 times the midlins dose, wen in contect with the ground. An eetimete of skin dose due to gropad eontmnhtion for tho Rongelap case would result, for example, In a of abut 2OOO rep to the dorsum of the foot, 600 rep at the hfp law1, and 300 rep at fb head if continuow exposum with IY, ohieldlng ocaurred. Some reduction dose rmdO&hd~I’SSUltOd flu~IOhhldding and me- ment, and it seems probable that the external bta dose hrn local akin eontnmlnation fer outwigbd thet from tb gmuad in importance. This le emphesieed by ths fact that alothine probably reduced the beta dose from the grow by 10 to 20 per cent, while it teaded to collect d loCaliso tla direct skis oonhnlmtlono

26 I Fig. 1.1 The lie area on Roqelap Bland, indicating the Ught, opr~lptspeof conatruetion Fig. 1.2 Nstagram nf proportion of total dose oonMbutea by various energy mglona from the fallout radiaa e 1

3SOO lWlO1 30 IN33 U3d

?G e TOTAL DOSE IN AIR (r) 8 C

8 33

t:

31 P I I I 1 I DEPTH DOSE IN PHANTOM MAN I I INITIAL RADIATION 1 RESIDUAL FIELD I I --- I I I I I I I I I

. ,.. . -_I*. 2.1

It -88 kmnn whbu that the exposed p-8 had lWCdVOd a aignificaut muut of pemtrating radiation to the entlre body, extensive contamination of the skin and possible Internal deposition of radioactive materhls. It ws therefore decided that cllnlcal obsematione would be as extensive and fTeqwnt as facilities arrt / pereonnel pemltted in ordex to rwognim and care for radiation effects as ear4 possible. rO~orclInglpcomplete initial hl8torf.e~

Ufld mSfd UXEIUhStbE6 With -uB fO-W-Up MbStfOM W6P9 carrbd out. Sumeye of the skln were codlucted at freqmnt h- ternale ad the detailed skin fkdings rn raported in Chapter III. Extenltive bematelQgh18tfudleswere oondueted, the detailed realata of which are presented in Chapter IV. Results of examhatione for mlmry exoretion of radioisotopes am reported in Chapter V. In addltlon to perm exxminntions, routine sick ad1 me held tnlce dally. Medical cere was available at all times rudl bspital faoillties were availablm at the Kwajaloin &mal Dispensary.

& vi.. of tha wldoeprrad Conpuating 0pipiOnS in regard to the value of varlow Frropbylsatlo and tbre~iameesures in treatmat of radlatlozr affects, it warn dw9dd in a&we that therapy rouzd not be given arbitan~llpbut muld be Instituted RE Mlaated clln- i~allyfor SpOC~lCooaaitio~ 011 80 Mlvldual besia. Eomer, if severe granulocytopmnh dewlapad (belor loo0 celh/am) the propip lactic we oi antlbbtior, nuld be aoneidusd on an Mlvldual basis, pshele bldtrnnafmion~ would llkerrlae ba resorted to only in thom

39 eases depelaphg frank atmnlao

2.2 &4D m Several that developed durhg tbe flrst dap or two after expsura probabu were attributable to rsdiatlon. 1tchI.q a& buxnbg of the skin aad eyes during thJs period oacun-ed in over one quarter of the Rongelap population, to laem extent in the Ailiqpe to a *wg ellghf extent knericans. and * in tht The skin symtolmrtoZogg might ham been due in part to the marked a&Un- lty of the fallout naterlal (calcium We). About tw thMs of the Ro~lepgroup repOrtA mume during this ear@ period ani om tenth of the groap rsported vomiting am3 diarrhea. Only one Alllugme lndivlduel reported LyImea. Ths people of Utirik d the Pmericans developed 110 s&ne or egmptmw that mlght be related to radiation,

With the cnception of the development of E- leeions and epila- tion, physical t3XaIDhtiOM at xm time revealed findjags in any group thet cauld be attrlbuted wlth oertakrt;p to radiation. The various clinical oondltiona euumuntered in the amst severely expos- ed groups - not remarkably dLflersnt fron those seen in tlm least mxposed Utirik group, The skin lesions and epllatlon made their appearance begimriog about the 12th to Uth post sxposnre days. ;a 2.3 GLW;a t 01 I

Xitho@ detailed hematological fMings are presented In C-haptor I?, certain considerations of the relation of clinical to hmfologkd fMW6 discussad here. 203.1 CoM ta Between the 33ni end 42rd post-exposure days, 10 par cent of the ibngehp iodivlduals reschsd an abwlute &ranulocyte lopel of lOc0 per cubic mUimeter or below. Ths lowest aomt observed during this perm wae 700 granulacytes. Durfng this Internal the adpirsbillty of givbg prophylactic antibiotic therapy to auch in- dividuals was carefully reaoneldemd. Roneper, ps-opk@actlc anti- bictkcs wre not instituted beaausa of the fo&wimg COns~WdtiozIae (1) Ail b3ividuSh mere under continuous msdical obs~atfou so that infection would be discovered h kts esrliest etageso (2) Sfnee some ~ivkluals require antibiotics for long periods of time if infection ocmd, the psmatii adminiFtrati0n of sweh druys nollkl not only possibly obacm medical indication of treatment, but qkti po'canl;ial?Jr lead to tkm dfmdopmant of drug re- s!.utrnt orgmiam in an lnc?ivklual wLth an alm@ lowered re55stance to infection. (3) Thex is no accurate kmw1eQp of tho rmnbei. of granulocytes rq-&md by mnto prevent the types of iaZection see11 in aganulo- CytasiEs, (4) The observed situation was mt strickly wnpareble'to agra~- ulocytosis with an aphbctic -w due to potentially lettal dosse

41 of radiathn. In the latter umtance, -eo fall rap- and there are practically mm in the ciroulation when infection occurs. In the ypeeent group of ~viduphexposed to radiation, although met counts rere apFoprlmete4 -4'0- d mstba

fall to that he1 gradual and then, .M 8OlrID eVideuw Of gnKr-

ulocpte regeneration. Whlte counts ware mpeated at 3 or 4 day btmb on all of the expo& iadiPidusb and more fhquently on those with tho lorr- est Dounta, Those with symptom or elwated teaperatmas were treated on4 &tar an attempt to establish a dhgmeis .ae made, wen if a period of observation waa mces8ax-y. During the obsema-

t!.m park:?" t:ib ga+.iant; ~.i.:-exci3ai kt fmqperrt Memala and the tmperatrm, uhecM fer hours. Tventy-seven Mividuals had total leukocyte counts of 4000 or

belor or absolute mutmphil oaunts of 2500 or less at ~rmstim durbg the peribd of obeervation. Of thew 27, 13 had sgmptoms of dieease that rsqulred evaluation for posefile antibiotic therapy. Elmm of the 13 bad severe apper resplra- hfectlons, one in- div5Lual had abdoninal paha aOi: fever, and one ha.3 urticaria aith fevsr. The incidence and type of ggmptoms in the group with &u leukcqte counts did not differ materlfilly from those in the nmeM- er of tha popnlation aad it appearad that the occukz.81108 of disease and tha preaence of leu€qmnia ma cofaeidental. The 13 insfaneas

in wmIt was mmesary to consider the UM) of antibiotic themam in neutmpenic lniivlduab are srmmarised below:

42 Eleven of the 13 Mividuals had 6e~ez-ewr nepirato2.p in- fectiona. Eight of these had malaise, sore thrPat and nasal dis-

charge, and tamperaturw that varied betaeon 99 an]. 101.4 and then fell to norm1 within a 12 bur period. Since th rssponss of this

wup fo upper mrplratar~infection appearad Sentleal with that of Mividualr without neutropenia, no therapy was given. ho of the ll had marked malahe, badache, abdominal pah, musea, diarrhea, ard high fww. Both m~ children, om age 7, the other

age 2. In both iostanoes, the mymptama were out of proportion to I i. tha pkpfcsl CM-, which were negative -apt for oorpra enl mild pharyngeal Znfection. The eeven-year old child had a tampera- tmof 102-6 when firat wen and four hours later, 1% Tbs twc- year old child had an initial t-tnre of 101-8 degree6 which

" I rose to 103-5 degree8 in I hours. Both were given intramuticular procaine pehlllin when the sharp rise in temperatum occurred, and both mere m~.Omaticand afebrile the foUowbg day. P mecord injectkin of ponklllin wan given at this time, and therapy wne din- continued. In spite of the fact that the neutrophile remained de- premed In both cases long after the febrile episode hed p~ssod,

both individuals remered aad hsd 00 frnther illness. In Figure 2.1 th6 blood counts and platelets of the two-year old patient

acd the time of the occurrence of the febrile llln~~~EZW illuatratB- ed. A arm-year old bey had symptoms of upper rosphtory infection for several days before being brought to the clink. Whsn he was

43 6883, his temperature was 100.8 degrees. In addition to the cava

there was pharyngeal injection and nuolsrouB coarse rfionchi throryh- out the chest. A diagnosis of upper respiretory iPfscthn with

associated bronchltis'wes made and the child was given a single Ln- tramuscular injection of procab penicillin. On the following day no rales or rhonchi were heard, the temperature ms 99 degrees, and he remiwd asymptomatic without further treatment. One of the 13 Mividuals was a SO-par old man who reported to the clinic with neaknees, nemousness, mild ebdominal pein ard shooting pain in the upper anterior chest, bilaterally. He appear- ed moderately Ill, temperature was 99.6 degrees and the only psftlvo physical finding was mod6rats tenderness in the right upper quadrant of the abdomen. Since his granulocyte count remained low on repeat-

ed examinstion he was Been at frequent Intervals, Elthin a ten- hour perlod the temperatme rose to 101.6 degreos, following whlch it fell gradudly to abdomlnel continued ! normal. The teIxlerness for 2.4 bours and then gradually d1esppa;rbd during the subecqwnt

two days. A dhpaf8 Of cholecystitis was made. No speclflc ,. i therqy wus given. In Plgure 2.2 hie white blood count and plate- let counta in relation to the appearance of sgmptorns are shown. A female aged 36 developd generalized urticaria, fever, end

headachs. Urticaria adfever subsided within f3 burs without aq therapy 2.3.2 ZLe telet Corn t& All Mivlduals with a platelet count of 100,000 or less were examined daily for evidence of haraorrhags into the skin, mucous membranes, and retiaae. Urlna was exanined for red cells arid al- bumin, end women were questioned concerning excessive !nenStWtiOno There was no evidence of hemorrhage into tissues even though ll individmb reached pletelet levels between 35,000 and 65,000. Two women menstrueted when their platelet counts were 150,ooO and l3O,OOO Faepctively. Bot*. menstruated several extra days and thoyht " 'I that the bleeding was mora than usual but not sufficient to OBU88 thea undue concern. 2.3.3 &matocrit Chepserr Nineteen MlvLfuala in the Rengelap group had hematocrits of I 35 per cent or below; honsvsr, none of these were below 31 per osnt, Nine of the 19 were children, aged 1 to 5 years who would be expect-

1' I ed to have a hmr hemtocrit than mrmsl adliltsj four were over 70 years of age, in which age group e decreased hematocrit is frequsnt- ly praeent rlthout obvious etiology, Iko of the 19 had had menorrhy;Sa prior to the determination, two mar@ 3 to L months pregnant and had not mceived supplementary iron, and two were young women. The lon hem3tocrits that were obserps3coul.d be explained on the basis of nom1 pSyaiologicalvatiations rather than to the effects of irradia- tion on hematopoleslo. 2.L The Effect of an &i:eaic of UDD er Remiretom Infection on an mlstedPog\Jstl on Between the 27th and 421ul post-expsure days an epidemic of upper reepiratory diseases (URI) occurred. FifQ-elght per eent of

the hcgelep group ad 56 per cent of the Ailingnae group were in- 45 volvad. wenty per cent of the affected hdividuala dweloped symptoms hetween the 2?th aad 32ni postaxporure daye. blng the perid in rhich lndividula mera developing egmptoma of the respiratory infection, the mean leukmcpte count of the entire pop+lcrtion did not follow the tzslld of deateeae. On the contrclrp, fifty-tm per cent of the leukocyte count0 were observed to inorease to higher lepsls, the Increase belug dm primarQ to granulacptrs (See Chapter I). shoe ths iacmase in the mes &ramiloogte couat of the entire popation occ~about the time'the epidemic of URI developed, It seemed perthefit to determine whether ln individual imtances the increase mas spontaneous or mas ln noma nay related to the presence of respiratory infection. The relationship between the observed leukocgts increase and tb preeenae or absence of upper respiratory eymptoms in the Individuals exposed to radiation suggest- ed that the two effects were unrelated. Of the 6L individuals Prom RangaLap, 2'7 had no respiratory infection and of these 13 (4s per cent) without UFU showed a rise in leukocytes; 37 had the in- fectbn, and of these 24 (53 per cent) showed a rise; 7 of these 24 shoned a rise three or more days before symptoms appearet. Of the 17 from Bilingnae, 8 had m reapkatory lnfection and 3 (3'7 per cent) of these shored a rises 10 had the infection, of these, 3 (33 per cent) showed a rise in count. It is also of Interest that not only the irradiated iri6ivAuals developed the respiratory infection but in addition the medical personnel irmolved in their care and study also developed equally

46 aevere respiratory Wectlons. The respiratory lnfectlona consist- ed of moderate malalee, wra throat with promfmnt lsmphDkl follicles, pharyngitis, moderate fever on the first dey, and a pdent naeal ad tracb:.d. discharge for 10 dapsp

2.5 Epepapison with the Utlr- of Diaeaaes Seen In the ! the Period of Obne- The diseases that were men in the Rongslap a wegroups during the perlod of obaematlon are llsted in Table 2.L Hone of these appeared to be related to the effects of hadfation, either dlrectly or as a result of the hemtitologic disturbances. For com- parison, the diseases that were seen in the Utirik pup durfmg the period of observation are li8tsd in Tablo 2.2. The high lncldence of gastroenteritis ln both gmqm 1s probably due to the Marshallese keeping periahable foods unrefl’igerated fer brig periods, and was not seen after this practice was stopped. It would appear that 8 higher percentage of the Roagehp-Allhgnae pup devebpad upper lWSpbatO~bf0CtiOMcompared to the Utlrik group. &never, all of the ROngelap-Allhgnae group wre questioned concerning men mild eymptoms of DRI, whereas only those of the Utlrik group with severe symptoms of URI came to the clinic for treatment. Similarly, the per cent of the RongelapAilingnaS group that developd purulent infections appears higher than the Utirik pup. Boneoar, the dlssases are tabulated for tha period of observation of each group, and the Utirik pup was observed for owhalf as long sines they were move8 to another island anit was evident that further study was unaecessarp, 47 1

The bodyplght of indiriduals In the Bongehp-Aillngnae group was followed routinely. Since they had an unrestricted diet and all ate well, their ch~npin rslght might be taken as an indication of any diaturhsnce in their over-all metabolism. The might chenges ere sunnarbe6 in Table 2,j. It would be expecteP thst sftLfin a period of 6 neeke, individuals below 16 pars a& particularly those below e yeare mukl gain some wefght. The fact that most of them lost weight mny indicate that timy received e dose of raiia- thn sufficient to interfere with normal metabolism. In spite of their ralativaly inactive life and hsarty appetites, most of the adul-cn also lost weight which may indicate soms bterfersnce with thelr normel metabolism. There is little dFfference in c:-mewed weights betrean the Rongeltip and Billngnae groupse It a7pears that the difference in doses received by the two groups did not dfi- femntial4 affect the* body weight. Rlether the failure to gain wc&ht rns comwted with radiation or ohanges in enviromnt ia opon to question. Unfortunately, the weight of the Utigik group we6 not 3ystenafically followed and no satisfactoq control a,cisto to aid h interpreting the loss in might of the RongeLSp-Allingnas grolr,, 0 2.7 a Wfcctr, on- Fv Four nomen in the Rongalap group W~N pregnant when brought to

KWajsleh. Tprc were in the first trimsster, one in the second trhester, and om in the third trimester. Nono of these DomclLL had sbnornlal symptoms referable to pregnaney,,ad as far can be de- ?.ermine3 pregnency contlnued b n nom1 faahion. In the ailinpe groups one woman was in the secod trimeoter. No abnonnallty was dotectel. Fetsl iaovemonts were unaffected in the indivi3aal in tha third trimester. The hematologic chwes of the pregnant WXSL are listed in Table 2,+. Tsro Individuals ln the ffrst trimester hnd mcrkel depression of phtelhs but at no "ue was these ay vagine1 bleading. Howovurs all of the pre,pant women were blood- type3 as n precaEtlonsry measure. The radiation dose received, to the fise of this report, did not have B deleterious effect on pregmncy, She the dep6rture of the medica?- group from Snejeleic, one apparsntlg normal bab has been born, 2-8 Q&ymsbc or the Use of Au%lb&otict.in %IdsCmm a& Jg -RfIdIatiOon hirrx Ikare were few ini.icai;ions for tho USG of antibioticfi w3an 43; principlerJ of treatnent prwibusly mantionad Bere used. Indlviduls in the lbilgahp and Allingnae gd.oups that received antfblctfcs am llstad k Table 2.2, Of the lndividuale t?eatsd with the anti- biotics,? ?.he first three receive5 It prop~laoticallyend it woulc. hcve beol: Mlceteci ha6 thq not been lrrelliated. Tha bdlcstior for its me in the next three na6 questioncble, Th~mVQZ a def- kite liidicatlon for ita use only in ths wxt thre? Lodivuduels an3 s&n It nouXd have been given for sLicoxitltlom In unirra6lnf- ed indfriduals. nle lest two lndlvi8uals nith furuncles would pmbw hl,v have mspondsd eqully ne11 to surgical troatrcent alone, since

49 In general, it can be concluded that human belnga with the degree of deprQ6Sbnof hematopoiesis noted do not need antibiotics pmphylaatically. With seem degrees of radbtlon injury msult- hg ln a greater depreeelon of hematopoiesis, prowlactic anti- biotic therapy may be indicated in seleoted cases. ff the nunbr of individual8 is muell emugh BO thet changes in the blood countp tenperature, and clkrioal evidence of iniactlon can be followed ohsely, it would appear that antibbiotics should not be started until there 1s a clear-aut clinical indication fox the uBe of them ageate, 2 1 1 1 1 1 1 1 1 1 1 5 2 10

51 Diseases that Appswed Dming Observation of tb utlrik Group

Dlmasa

~~ ~ ~ ~~~ ~ osteoarthritis 4 Epitheliana of ankle, with necrotic dqawration 1 Chronic bronchitis 1 Furuncle of calf 1 chronic bronchitis ana bronchlectaeis 1 Abscess of sole of foot 1 Carbuncle on right thigh 1 Tooth axtraction 3 Fwip infectfon of gum and palata 1 Contusion, trsrrmatio 2 Gas”uroenteritls 30 Uppn respiratory infection6 15 Arteriosclerotic henrt disease, dsconpencrsfed 1 ~lonephrittis 1 LMsct bite, with mked palpaoral inflermmation 1 Choriwatinitls, wiolowa etiology 1 T.h3mbopNebitis, an”*cubital ve%n 1 Itsctieo 3 3pnenorrhea 1 Esfo~atiiwdermatOp~@OSiS 1 Ect?apion, right eye 1 ~~th 1 Benign mnaionwith headaohe 1 ri~pa~~~tropiawith hoadacke 1 I3yopie with headeehe 1 Fun-pue infection, auditory aanal P micilownas with cyskitls 1 T5ma 1 S:mle headache 3 1 1 1 1

52 Table 2.3 Weight Changes, bngelep and Ailiagrae Groups

Eelan 7 mars Above 16 BEL, ROWXLAP GROUP hbber obd 17 36 IhmibQi' that gained 4 nelgh-k u

Averqe gab, lbs, 3.5 spreac: of goin; Be, 1 - ll.35 ?J* that hS' 21 nelginf-

Averwe loss, lbs, 2

Sprenr. of 1O3Sy Ibs. 0.5 505 Per cant of group 77 thzt lost wei&ht

.,knEEME GROUP Rusber observed 7 9 I Nucbar that g-a 0 3 weight.

! Avenqe gain, TbLbo, - 2*7 Spreac? of gain, lbso - 2-4 1hber thnt lost 6 6 weight

Averwe loss, lbsc 2 2 ! Spread of loss, lbs, 0.5 - 3 Oe5 * 4eD Pgr cent of group 88 67 that lost welght ‘Irlnasbr of Lowest Platelet Zonest Isaweat Pregnancy count ViBC Nwtrophile Count I I

54 Pat:.ent condition pb, 1 Deep dneite sbqh of epidemia of foot 2 Tooth extrsotlon 1 3 Tooth extraotion 1 I liflmmd tonsils alth hfgh 2 temperature and Wf 5 URRI end bronchitis with htgh 1 temperature 6 tRIo severes rrlth phaqngitis end 2 hlgh temperature 7 Fq3.d faogressing mdembLng 2 lnpeflgo 8 keuuetic gangrene of foot 7 9 2ytitIs 5 10 Fwunole on buttook 2 u houncle on forehead 1

CELLS a IO3 e

dnrk skin. An a@hna uas not seen in the vhite skinaad bricaw expeed on Rongerlk, 3.2 skin lesions 5-201 General deal’fFthn Skin lesions first appenred in the Rongelap graup after 12 to 15 doye and in the Billngnas and ROrgerUr pupa after 20 dtlys,

Thsre M no &In lsaions in the lptirik grorx~~There was considei- able differeme in the lergth of tine rtaaeaaarg for fhe dweI.0pmen.l. of Che various lesions8. !?owever, It maa f-. that there was a COP sietont pattern In the tquentkl dawlopnent of lesions on parim. p&s of tho bo@, The principal lesiom nhicb developed oc various expeed portions of tb occucFed mu&hly in the folloning sequential order: acelp (wlth epilation); aecl;, axillmy region, entacubital fossae, feet, mms, legs, end trunk. Lesions on the flexor surfaees %en&& to precede those on the extensor &eess (:e3 Table 3.1 for the tiDe of qpearance of oarlouo lesfonu), A clear cut primary e&bria va8 not seen9 mr was a late ery- theme. In a few casesp them vas oonsidsr&le scratching of the 6k.b due to -itis prior to developent of gross lesions, In these CEAWJ, en ayt,heron of questionable etiolqy mas obserwd, This eqitbma my well have been due to the acsate~,Wythana ma not observtd precediw dowlopoent of nild lesions in the white and negro Amer5cax of the Rorgerik gorrp. l’ha fbst IndicatiLon of a dewlopbg leslan naa an fnffease ir pigmentaAtion, Theso pigmented QFBLIS appeared in the form of muls8) papules, raised plaques, or larger amas of nacdos and papdes (1 to 2 m in &.ameter)

ClUStarS and e0U~tl1.ne6coalesced bt0 larger 1eSiOM. The latter were charocteri8klonlly fcnmd on the aoelp, neck, and the antecubital fossae, The raised plesues vaxied in sFse fmn a few udllbetere to several eentinetem in diameter, were thicl., m\yh, dry, and had a leathew feel. This type of lesion oacurred predominantly cn the feet and in the entermbitel fossae and to a mch lesser extant on the ne&, hmas of increased pigmentation elso oa-d on the 11DiImp tnmk, end on the faceo The majority of the lesions were superficial.. Tn thee lesions: vesicles mere not obserwd. A feu d.sp after appearance, dry, scaly desqusmation occmrad In the central porkion of the hyperpigmented areaso The deequametion left a pink to mhita spithelimn not remrk- ably dlffemnt in texture h.m the . skin. As ths aesqus- nEtion proceeded outward, the areas developed a charocDsristic appear- ance of a central deplgmented area hinged wiLh a lgprplgrmnted zone. At a later stap, pigmentation began in the central arem and spread outwards. After a fer, weeks the cycle was cor@eted, le- in most instances a mlativefy normal appearing skin, Approldmtely 20 per cent of the Fangelnp pup developd les50ns which were more aevareo Thene lesion8 dght be oonaideivd

69 compmable to sacond degree thermal burns. The deeper lesions occurrad prlncim on the feet and fo a lesser extent on the sed? aad neck and in one cese on the ear. Vesicle fomation uae not

62 oommon. However, on the feet, 6ome large bullae Lfter a fer days, the hyperpigmented lesions shoved mt desquamation with meepinp and crusting, leaving depigmsnted raw surfaces of varying area. Same of them leslona became eecondorily iafected. Epithelium rap- aoversd the ulcerated areas within a meek to 10 days. Plwntatinn followed during the next few weeks. Ae healing occurred, som of the deeper lesion6 and som of the less sew28 lesions developed a thiclcening of the skin with an *orange peel" appearance ard a dusky, grayiah-bmm color (See Plate 3.4). In Table 3.1 is tabulated the inc¶denoe of tb verfoue types of lesions in the Ronplap with a breakdm as to age and the mediar time of appearance for tJm dFungnae and Rongerik groups am shorn,

3.2.2 &g&g ti0 n and Ill*eonof SD~CL~S$QQQ.

10 and forehead leafOM began the& appearance I2 to l4 days foollooring exposure along wlth epllatfon in the RangaZap group. The skin lesions were maculopapular with a spotty distribu- tion. They are concentmtd in the areas of epilation. These lesions are illustrated in plates 3.12 to 3.16. Scalp lesions continued their appearauae over a period of about n month, Thus, groups of lesions in various stages were pweent in the came in- dividual. "hb ms partloularly notable among the chfMren. Ths incidence of scalp leeione ma greatasf in the 0 to 15 wegroup (See Table 3-11.

63 were the most aommon and began their ap- pearance a few days after the scalp lesions. These lesions ap- peared as ~rplgmentedmacules and ?pies which spread and coalesced into raised plaques. The lesions u~uaw appeared first or, the side and front of the nock and upmad backwazds. They were mre common and mom severe in women. Plates 3.1 through 3.L and 3.9 illustrate neck lerions in tbparlous stages of de- velopment. Some of the deeper neck lesions tearled to occur in women where thek tuck hair touched the* necks. were maculopapular, less abundant, and de- veloped simultaneouely with the neck hslone. These lesions are illustrated in plates 3.10 and 3.I.l. The axillm~lesions were more cornLonin the young chlMmn. -leatons appeared about a week later than did the neck and axillary lesions. These are illustrated In Plates 3e9 and 3-10, Thc foot lesions developed later than the ledom of the antecubltsl fos~ae. These laslons were located mhly on the doiwnn of the foot between or on the toes, Tbeg *re initially chcractorieed by large pigmented plaques with subsequent bullous formation and in eight cases raw crusting l~siorrsof v~rylngde- gree followed the bullaeb The foot lesions we- not as common in chLldren under 5 years of a@ a8 in the older age groups. Sequsn- tiol lesions in a U-year old girl ara shown on Plates 3.5 to 3.7. One of the more severe foot lesions is shonn in Plate 3&

64 were the most common aad began their ap- pearance a few days after the scalp leslone. These haions ap- peared ae mrpigslented macule6 and ;.qxles whiah spread and coalesced into raised plequss. The m8%0n6 wuaw appeared first o~jthe side and front of the neck and lpread brckwds. They mere more comon end more mere in women. Pla’ies 3+1tbrough 3.4 and 3.9 illustrate neck lesiona in the parIourt etsges of de- velopment. Some of the deeper neck lesions tamled to occm in =men where thelr tuck heir touched their necko. -a -a were maculopapular, less abundant, adde- veloped simultaneoualp. with the mck lesions. These lesfo~are illustrated in platas 3.10 and 3.11. The axillclry lesions were more comrbon in the young children. &&cubltalfeF_eae- appearad about a week later than did the neck and axlUarg lesions. These are Illustrated in Plates 3,9 and 3.10, Tho foot lesions developed later then the lesiona of the antecubital foslrae. These lesions ware located nahly on the dozsum of the foot between or on the toes, They -re initially chcractorimd by large pipPented plaques with subsequent bdllaua formation and in eight eases raw crusting lesions of varg-lug de- gree followed the bullae. The foot lesions ware not as common in children under 5 years of ap as in the older age groups. Scqtmn- tin1 lesions in II U-y-r old gLrl are ehom on ;.latea 3.5 fo 3,7. Om of the mre severe foot heions is sbwn in Plate 3.8.

64 Jasiona of the had. m. 1em. and a were leas com- man, lesa severe encl developed kiter, Areas of lncmased pigmen- tation were scattered over the abdomor~, cheat, arme, legs and face. Increaaed pigmentation of the sldes of the Pace is illustrated In Plate 3.4. A atrikhg aarly lesion was an ergthematous, weeping,

excoriating lesion sworurling tho (UII~LIuhluh wcurred in revera1 of the babies and a few of the older people. Them lesions mre severe initially but healed rapidlyo

bst of the blarehelleae had multiple leSiOM. The combhation of epfition and the contrasting hyperpigmented and deplgmented areas adjaoent fo normal sMn presented a strildag appearance. . The multiple leoione are illustrated ln Plates 3.8 to 3d.L 302.3 agsSmr e v

-0 It ie mt feasible to quantify accurately the sW9ritr ad extensiveness of the skin lesioaa in the various pupso Bow- ever, It war the uniform opinion of a11 observers that the moat aevere and eXeenslvo lerlons wcurmd in the Rongslep group. The lseions that developed in the AllhgDRa group were much brs smm and extensiw,and the Rongsrik group (Americans) had only mild lesions. Skin lesions were completely absent in 60 per cent of the Rongerik group, as eppoeed to appmx?satdy 10 per cent ln both the RDngelap and MUmgnae groups. Tnul8epidermd necrosis occurred in 20 psr cent of the Rongehp and in 5 per cent of the Ailingnae people- No lesions of this severity were seen ln the Rongerik group, 65 The hsiona appeared ear&r in the blIgUhp pap SWkTJ&lx

a higher dose. The cMmparl6on of the Incideme of *pilation d neck lesions and time of appeannoe is illustrated in Flgrtre 3.1 for the Rongelap d AUagrae gmqo 3-24 Seven biopsies were tahof neck bsiona ad om of an dsryhalon during the thM to fourth week dtar sxposure on the Rongelap pople. 5m lesions biopsied at that time were in the hyperpigmsnted stage with llttle or rm desquamation having wcinredu Most of these biopsiss were taken from Mivlduale rho shorsd bsions of greater than average severity. A swod grow of biopsies from I the Rongelap group (repeated In three bdivianala) taken) four at tb seventh week post-caposme and five at the eighth- week period. These were taken from the mkand antecubital fossae. All of these lesions had bequamated and the depigmented skin bad repigmented to a dusky, gray cob aith some thickening ('?rPnge-psalR appearanae) of the skin. Bfopsies were not tabn from open lesions or R.om the feet for fear of infection. All blopey .lolmds healed rapldly with no secoxlary complloetlona. The microscopic finlings ere emmariced as follower to &th week. Transepldermal damage was noted with a few intervening

arcades showing less -e (Plates 3.18 and 3.19). Ths epidermis in the most extensively krpolvud areas showed considerable a- trophy aith fhttaetng of the rete pegs. b places the epidermis

66 was redwed to a thickness of 2 to 3 oells (Plates 3.20 and 321)0

Tbs cella of the vblphlgian laper showed pleomorphic nuclei, pyknosis ami cytoplamic halos, giant oeUa d inn few instancee multlnuoleatsd oells. Pyknosis of eella of the banal laper was commonly seen. Focal disorgadsatbn of the Malphlgian and baaal layers was usually present in the more exlanaively damaged arcades, Cells laden with pigment wore bequently present throughout the epidermis and lnteroellular pigment was noted in some f#atiOne. The stratum granulosum was neuslly atrophic or wen absent. Im- perfect keratinization aith parakerathais was risible ln all sectloris. &perkeratoela prasent ma also seen. The stratum oorneum was loosely fibrillated.

The arcades of minimal damage were usually found in me8 where sreat ducts approached the epidermis (Plate 3.19). There was an apparent increase in the number of cells and mitotic figures in the neck of the dwta and the adjoinisg areas where regeneration was underway. In these areas the stratum granulosum

RKS near normal width and pigmentation of the basal cells noted

In the more severely damaged mas was lacking. Changes in the dermis were laresly confined to the pars papillaris (Plates 3.18 through 3.21). Eild edema in some cases was noted. Capillary loops were often Mistinct and when discern- ible they fmquently were associated with increased number of pericytes. Ths endothelial oella showed swelling and were polygonal M .

in shape. Telangiectatic changes WON noted in areas where the overlying epidermis showed greatest damage with mhocyttle infil- tration surrounding the telagiectatic spaces. Chromatophores, filled with melanin pigment, were prominent in the superficial dermis. The fbelastic fibrils runnlng into the pars paps- lnris were often altered or absent. Little If any damsge was seen blow the auperficlsl pars retieularis. The hait follicles were narrow (Phts 3.22) in most instances devoid of shafts in this region. There was soma telangiectasis of the capillerg spaces bounded by lympho- cptes and monuclear pbegocytes in the soperficial pars retic- ularle.. Some of the large alastic fibre in this mgion show- ed slight swelling in some instances. No damage to fibrocyfea or collagen fibers was noted. Second series. 7th and 8th weeks ms t-exnosure. EDiderm&. In general, reparative processes of the epidermis appear-

ed to have been fairly good, except for a few persistent amas

of atrophy with narrowing of the epidermis and finger-like

,,. . i downgmwths of the stratum raalpighii (Plate 3.24). These occur- red in areas of greatest epidewal narrowing an3 the cells ahor

ed' rather prominent pigment content. There we= many outward epidermal excrescence8 covered by thickened stratum corneum which was still loosely lam,hted -- such phenomenon producing e rugose appearems which probably accounted for the "orange-peel*

68 like appearance of the skin noted grossly in the areas biopsied (Plate 3.22). In almost all instances the basal layer was in- tact with little or no disorganizstion noted. There were a

few scattered areas in which occasional epithellal cells with

pyknotic nuclei and perinuclear cytoplasmle halos occurred in the stratum granulosum and Malphiglen layers (Plate 3.23). .,,. ! There were occasional arcedes In which the epidermis, particular- ly the stratum granulosum, appeared to be actually widened. These occurred almost predominantly in relationship to the coa- tiguous sweat gland ducts at sites where the latter penetrated

the epidermis. A narnx zone of perakeratinosis ard amorphous

detrls wcs still present between the stratum granulosw an2 the lcosely laminated stratum corneum. Penlfs

The capillary loops in the dermal papillae, although present, were not uniformly distlmt. Pericyte6 remained In iccrease2. nmber but fewer lymphocytes were present. Generally, there appeared to be slight telagiectasis of the capillaries in

the pnrs papillaris and the superficial parr reticuloris (Plate

3.Z)- There was some edema of the pers papillaris (Plate 3.22). Scattered pigment leden chromatophores were irroe;larly dis- tributed in the papillary wer (Plate 3.23). In some cases hair shafts in the superficial pars reticularis were quite nar- row, atrophic, and occasionally absent; in others the hair shafts appoared nornal. Small hair folllcles (Plate 3.22) and .

secretom sweat ducts In some cams showed mild atrophy. Biopsies of three pignented mild lesionc, were taken fio~ two of the white Rongerik Americans. Only one of the three gave evidence of damap, which wa8 nominal and confined to the epidermis.

3.2.5 e. On the dw of exposure, itchiag and burnfng of the skin I' I ues prevalent. This subsided and for a period of ten to four-

toen days or longer there was neither subjective nor objective

evidence of skin injuqv. Itching and burnink; reappeared either prior to or in the early pigmentation stage. Kith the deeper lesions there was also pain. Pain was rather nrked with the foot lesions. klng the palnt'ul period nome of the foot lesions were also hot and presented a braq edema. A common 0. I complaint was a tenderness in the great toes medial to the i neils. However, vis?.ble lesions €n this area were Infrequentc,, I: This sympton wuallj preceded the appearance of paslesions

else hero on the feat. *any of the individuals who developed I, , peinful foot lesions were observed waiki-ig on tneir heels for several days. The plnfulness of t-he foot lesicns may have re- sclted from their greeter severity, and mey have been accentuat-

ed by the dependsnt nature of the foot. home of the lesions of tb3 neck and axilla were pairful upon turning tlm head or rais-

ing the arms. The acute reaction and pefn subslded after a fen days. There were no COlIStitU'&iOMl symptornn . r

The treatment of skin lesions WISE Larg~lynon-qxdfic.

Most of the superlfcial lesions were treated with calamine lotion with 1 per cent phenol, whioh in most cases relieved the itch- lne, burning or paln, A few of the painful hpperplgmented lesicns not relieved by calamine with phenol were treated with pontocaine ointment, with apparent success. R'ben the epltheliuu disquanated the itching was relieved by dally washing with acap end water and the application of a water soluble vanishiq type olntrnerit which kept the injured skin soft and pliable. Raw areas, which became secondarily infected, nsre treated by wash. hexith soap end by the application of amomycin olntmnto BUI~OUBlesions of the feet were left intact as lhg as no symptoms were present. If painful, the bullae were aspirated with sterile techn3+e to remove the clear strr7-colored fluid. A sirgle asplrat,ion was adequete since the bdlse did not refill One foot lesion developed an extensive, raw weeping ulcer. Pro~l!y- lactic peniclllln was given for two days, du-w which time tho lesion developed health.. granulation tissue. Some of tha leslor.! of ths skin of the foot remained thickened less pliable and ps:k,- ful artor fiesquamation. This was relieved by the use of VSEB- line or cocoe but%er to soften the tiasues. One persistent ear lesion did not heal after desquamation. Th56 we8 treated with wem boric acid compresses and washing vith surgical soup to remove the escher. Crtnulation tissue formed,and e?ithslirrm was slowly growing in from the edge9 of the I

ulcer when the initial obssnation period was tsmbtd 74 days after exposure. Upon resurvey six months after exposure healing was complete, with a depigmented sees remining as cvidence of the previouil ulcer. 3.3 Eoilation The incidence of and the of appearance of epiletion in the Rongelap and Alllngnae groups is illustrated in Table 3.1, 3.2 and Fig. 3.1. Epilation was fht obsarve3 on the Uth post-exposure day in the Rongelap group, and was confined to the head. The epilation was divided arbitrarily into thrse degrees ef sacrerity. *I+" epilation indicates 1OSS of hair without cbpious thinning; %?+ indicates a loss of hhfi sufficient to cause obvious thin qpots; and "3Q" Micstes an extensive epila- tion with bdd spts. Table 3.1 illustrates tht there ms a peater degree of epilation in the children (0 to 15 yeart!). Cver 90 per cent developed epilation of some degree in tho 0 to 15 years pup, compared to only 28 per cent in the older sge group, The preponderance of scalp lesione in the are60 of c?ilatioo indicates that radiation from the fallout material

G~I the skln la primarily responsible for the epilation. Tn the b.illngma group only 3 cases of mild apilation developed in childrszi

Slight regrowth of hair was observed in all lndividwl6

0 weeks after exposura. Hair regrowth wes complete and normal six months after expoaure.

72 3.4 FsL1 Pime$S&a ba unexpected obsemstion was the discovery of a hlulsh- brown pigmentation of the f5qernails which was first well documented on the 23rd post-euposure day. The discoloration began in the scm.iluner eras of the flngenulils (to a leeser extent in the tocx~rils),and tended to 8pread outward sometimes in streaks. Aa the discolored area grew outwards the eamilrmsr

6~-n*i’lually became clear. b a few ca.cw, detachment of the end of the nail from the ~llbed waa observed when the pig-

mentation reached the end of the Mil. Plate 3.17 shows pig- mented bands in the nails at 77 days. The discoloration of the nails was seen in 89 per cent of the Rongebp and 78 per

cent of the Ailme group. It anpeared to be a rarXetion re- sponse peeullar to the dark skin races since it was 8een In all of the American negroes in the Rangerik group and in mm of the white men. This lesion was not obaemed in the Utirik group, nor in the control Mnrsbellese. Since the nail pigmenta- tion occurred in individuals without skin lesions, it appear- ed to be the result of whole rather than local exposun. 3.5 Fac tors Influencinz tha Beveritv of Skin Le sione, 305.1 3e - t te The fall-out material was composed mainly of calcium oxide from coral, with adherent flsslon products. The skin lesions observed were doubtedly the result primarily of beta radiation from fall-out material deposited on the skin, wlth miaims1 or no contribution from chemical Irritation. The pmmm dose to the skin was small compared to the Seta dose, and thus was relatively luriplportant in producing the IOS~OM. -E 3.5.2 Erss-E From mailable data on the fallout material It has been calculated that 50 to 80 pe.r cent of the beta reys during the exposure period were soft with an average energy of about 0.1 Uev. Slnce Bo microne of tissue prduues 50 per cent attenua- tion or auch rad%stio&L), the greater pcrticr: 3f energy waa dissipated in the epithelim which is roughly /O to 70 microns in thlckmss. The remaining 20 to 50 per cent of the beta rays

were of higher energy, dth an werage of approximately 0.6 MeV. ! The latter would penetrate well Into the de- siaoe it takes 800 microns of tissue to produce 50 per cent attenuation eal., In addition, a use spectrum of gamma energies irradiated the el&. Appmxlmately ten per cent of the total gamma apectnn

WRS below 80 KEV which would be absorbed largely lathe super- fichl layers of the skin. The remainder of the gama apectrmn la distrllmted between 100 and 1600 KEV with a large proportian between 600 and 800 KEX. 3.5.3 Sbeelcel Dos e to the Skb There m practiaal ww to eatimafe the physical dose to the areas of skin where lesions were found. The entire surface of the body of the Rongelnp group received appmxhbly

71 175 r from gmnm irradiation derived from fission products distributed on the ground, trees and buildings. To thie 175 r would have ta be added the beta aomponent. In vlem of the high to betaAgamma ratio i.1 fission products, om might expect the total beta surface dose to the sMn to be lme. The maximal akin doses from the plane field of radiation are estimated In Chaptsr 1. To these doses must be added the contribution of the mstarial deposited on the skin. Tb letter ann not be calculated, or estimated biolog1aaU.y with aqy degree of accuracy. A rough approximation of dose recelved at the hair folllcles can be made ae follows:

The hak follicles must hve received a dose cormparable to fhs Lmm miaimel epllstlng dose of about 400 r for 200 KVP X-rays. Since regrowth of hak occurred, the upper limit of dose at the depth of the hair follicle mu& not have exceed- ed the permanent epilatlng dose of around 700 r of 2.x) KVP X-ray (?.?I* 3.5.4 protectlve Facto=. The lndividuels who remained indoore or der the treee showed some protection a8 compared ta those who ora in the open durlng the perlod of the fall-out. Those who went swim- ming or bathed were abo protected to vaxylng degrees. Small children mho rent wad- developed fewer foot leelone. Clothing, even a slngle layer of aotton material, offered almost complete protection, as was demonstrated by the fact that lesions develop I

ed almost entire4 on the exposed parts of,the bo&?. Since the IBSIOMpredominate in area8 where perspirs- tion is abundant such as folds of the neck, axillae, and ante- cubital fossae, it neems likely that the abdant perspiration produced by a hot, humld climate terded to cause the material to concentrats and adhere to these arees. In addition, the coco- nut oil hair dresaiag used by tb Marahalleae aoted 88 en ef- feotive collecting agent for the radioactive material. This was proved she the hair was the most highly contaminated part of the body. Ths concentration of radioactive material on the halr ms~haw been responalble for the large number of se;p leslom, epilation and the large lrumber and severity of neck lesions in women. The- was a delay of two and om-half days before satis- factory decontamination was possible, The presence of radlo- active material on the skh during this period may have kcreas- ed the dose to the akin. bwwer, the dose rate fell off rapid- ly and decontamination rould have to have been very prompt in order to be effective. 3.6 Corrsletlon with Bema t-cal Findf!%?a Attempts at aomlation of the severity and extecrivsnestr of skin lesions with maxhurn depression of platelet, lymphocyte, and neutrophil counts were made for indlvlduels In the Rongelsp group. No positive correlation VRS found. "hue the contsmh- 76 tion of the skin apparently did not significant% Contribute

to the total-body dose of irradiation., 3-7 pbcusai0p There he6 been little p~~~ioueexperiewe aith radiation dermatitis resulting from exposure to fallout moterial from nuclear detonations, and the general consemus until now hns been tbt the hadfrom fallout materlalnaa negllgibla. With the Hiroshima and Nagas& detomthM, fallout materid was not a problem since the bombs were q-rdeIP hQh in the air. The flcsh burns of the Japanese were purely theml.

Prom the preaent experience It is quite evident thst fOllOT-

lng detonetion of a thornomcle*-: weapon close to the ground, scrious exposure of personnel my occur from fallout nusterhl,

- ~2%at considerable distances from the site of detonstion, 'b

incident described 5x1 this paper is the firat example of hrge numbers of radiation buros produced by exposure to such fallout meterial,

bnlton, & & (3.4) described burna of tie hands of four

Individuals who were handling finsion product moterid followiilg

az experimentaltstonatlon. Aleo, follorring the blama,: dodetomn-

tion, there were a number of cattle thak davelop3d lesions dm to deposit of fallout material on their backs (3.,5> In addftlon,

there WQ~a number of sheep thctt developed hslona closely resemblirg radiation burns following a Nevada dotomticno Rowever, Luahbaugh (3.6) repcz3ed that the '17 characteristics of these lesions did not conform in all respects to radiation denoatitis. It is of considerable interest to oom- pare the present experience with that aoaepted in the pest a8 the typical course of radiation burm of the skin. The gross lesions of the hands described by Knoalton, & occurred from an exposure of about ow hour, resu)ting in doses be- tween 3000 and 16,000 rep of beta radiation ~umenergp crbout 1 m)with a emell gama component considered to be insignif%- cant. The lesions were described as developing in four phases: (1) An initial phase which began almost Inmediately after exposum and consisted of an erythema with tingling and burning of the hands, reaching a peak in 48 hour and subsidlng rapidl3. so that by 3 to 5 days them waa a relative absence of signs; (2) A second phase which occurred from about the 3rd to the 6th or 8th day and was characterized by a more severe erythema; (3) The third phase et 8 to 12 days, which was characterized by rekle and bullae for- mation. The emhema spread to new areas during the following two weeks, and the octive prooess subsided by 24 to 32 daysc The bullae dried up, and desquanetion and epithslhtlon took place in less sevemly damaged areas; (4) The fourth phase or chronic stage was characterized by further breakdown of skin ui:h necrosis in areas which were dameged sufficiently to compro- mise the blood supply. Atropky of the epidermis and loss of epithelial structures took place, which necessitated skin graft- ing in some caseso Robbins, & & (3.7) reported six cases accidentslQ exposed to scattered cathode rays (beta) from a 1200 Kv primary beam with exposum time of about two minutes and a mu@ 8SthtfOn of dose to the skln of between 1000 an8 2000 rep. Tho lesions described were similar to those reported by howlton, (3.4) with a primary ergthema developing within 36 hours3 secondery erytbeme. with vesiculation and bullae formation appearing about U to U days leter; and, in the mom snerely affected, a tertiarg phase characterized by further breakdoem of the skin. In conprison mith severe roentgen ray reactions these Investigator8 stress tha unique periodicity of cathode ray burns, relstive absence of deep damage to the sWn, lass pain, raplaity of heal-, and absence of pipotation. These points rjould apply to the Mershallese except for the multiphasic reactions end pfgnmntetlon. Crawford (3.8) reports a cafe of cathode ray bums of the hands which mors similar. to those dsecribed by Robbins & (3.'7)* Erperimental beta radiation burns in human beings have ben reportod by bw-beer (3.9) and N'Uh and Raper (3.10). Both in- vestigators used P32 discs applied to the flexor edaces of the ms, forem, or thighs for varying lengths oi' time. Iow-beor reported 'monaphaaic" skin reactions. Re found that a calculat- ed dose of U3 rep to the first millimeter of skin, Qmrhg self- absorption, produced a threshold ergthema. D=yp scab, desquama- tion WES produced by 7203 rep in the flrst millimeter and bullous,

79 y;et desquanation was produced 17,000 rsp to the fFrsf milli- meter. Erythema developed In 3 to 5 days, followed later by pigmentetion and desquamation with higher doses. Recopery mas obserrred cith doses of 17,000 rep. The lesions later shove3 de- pigmented centers with hyperpigmented edges (also seen In the present lesions).

Firth and Raper (3.10) pmducttd primary erythema within sk hours after exposure to e dose of 635 to ll80 rep of P32 radlaffon.

Kinute vesicles with dry, spotty desquamation wa5 noted with 1160 rep at about the 5th tc 6th weeks ~stt-exposure. Following the detonetion on 1 brch 19XI 23 Japanese fisher- men were contaminated rith fallout mnterial. Apparcsntly they

~.'9reexposed to roughly the same total-body dose of radiation e8 ere the Iiongelap group. The skin lesions which dweloped are de- scribed by brton, & & (3011, 3.12). Lesions developed which vsre similar In most respects to those seen in the Marshiallese people, m-d were characterized e pigmentation, desquamation r;lth depigmentation, spotty epilation of the head and ulcsratloilo 2aveloping particularly on the scalp, ears, neck, and hand~(tho latter pmbably from handling containbated fishing liaes)*

Erythemt r:ld vesicle formation, a= ne= as infiamntion of tile -6

W~PF am pominent then in the bahallese. Pigmentation apparent- 4 w6s not as prpminent ia the Japaneae. The 195iOna appeared a-rlier tl--3. i.u tLo Ma-ci~a.Zaoe k~bcut7 to 6 dap poat-e&a:u.8). 80 n AE in tho fLarahallese the lesions occurred maw on exposed partr of the bow not protectEd clathiag. In addition to the Marshallese and Japanese, smaral Navy men on ships ln the test area developed a fer small pigmented lasio~sof "belt-line" distribution, apparently die to fallout wterial. The lesions reported In this paper when compared to radia- Cion lesions described In the past presented certain dque features which merit further discussion. The early symptoms of Itching ad bwof the nkIn and ape mere probably due mainly to skin hadlation from the fallout metcjriai. Bowever, the chemicelnahms of this material mey have coztributed to the Irritation. It has been mted (3.13) thet krltntlng chmlcals applied during or shortly efter irradiation enhance tie effects of radiationo Thcr lack of promhence of an erythema was mteble, partiaul6r-L ly in view of tho severity of EOQ~of the lesions thet developedo r;ilLielmy (3.34) states tmt erythem onlp occvrs when the dosc L-eechhg the papillaq k7or exceeds a certaik level. Perheps the ciose to th dermis zas Insufficient to evoke the response. On %he other hand, the darkness of the skin end th. developnt of ~erpi~.sntetionmay have maslod an erythema. Ucmscopically,

2 sriperffcial hypremio was not 8 notable finding, AMh and kper (3.10) pcbt out that they were improased

81 in their studies on P32 radiation of the human skin with the difficulty of distlnguiahing between true erythema and tanning, particularly in the skin of brunetbsindivfduals. Color filters were not available to aid in distingullrhhg ep erythema as suggest- ed by Harris & & (3.15) In general the latent period before develoment of obvious aigns a& symptoms for all radiation injury is inversely propor- tional to the dose of radiation (3.16, 3.17). In tha present series of cases the relstively long latent period is suggestive of a low dose of radiation. However, the wide spectrum of beta enewies and particulste destribution of radioactive material drastically altered the depth dose, as compared with that in previous experience; hence strict aompa-isone cannot be made. The later dwelopmeat of leaiona in the Alllugme and Fkmgerik groups as contrasted with the Rongelap people is in keeping rith the relative severity of lesions noted. A Unique feature of the present cases was the appreckble differences in latent period observed for lesions on various pb-ts of the body. These differences cannot be explained entire- ly on the basia of severity, since the severe foot lebions de. veloped after most other lesions. However, the severity might have been a manifesfatlon of the dependent posi%loa of the foot rather than greator radiation injury. hsions on flexor wr- faces in general preceded lesions on extensor surfaces. The 82 present data suggest that the latent period and radiation sen- sitivity of various sMn areas may differ. Fmvioua work has shown that flexor surfaces nith thlnmr epidermis ere In general more sensitive than extensor surfaces with thicker epithelium (3.13)e The destructive d atrophlc changes of the epidermis, die- turbances in keratinization, ani atrophy of hair follicles are characteristic of histopathologic radletfon injury of the ~kin(3.9~3.13~ 3-I!.E, 3J9$ 3.20,3..?1 vo 3*31). Swere injury to the dermis and blood vessels was not observed. The minimal dermal 4- with severe epidermal injury is in keeping u5th the low energg beta component present and the merked decrease in depth dose over a distance of a few mlcrans from the emface.

g3,,-lpipantation of injured areas was a consistent find- ing in the Akrshallese, the Japanese, and the American Negroese Pigmented lesions were also observed to e lesser extent in the white Bmericans. Pigmentation of this nature has not bwn de- scribed as s constant cbaracterlstic of radiation damage to the skin. With respect to the ragid heeling, the vesicle formation, ani absence of late brealtdorm of the irradiated areas, the leeione resembled a aevere sunburn.

Them is DD satisfactory explanation for th3 darker dusky- gray color that appeared in some of the skin lesions as heal- progressed. The color changes may be due to alterations in local pigment production, vascular changes, or a thlnnhg of the epidemis, rendering it more translucent with resultant darker appearance of the pigment leyer. Later biopsies may -lain this phaomenon. Them are features of the haions described that appear unique, e.g., the abserrce of visiable multlpbaslc responses, the presence of early hyperpigmentation, the long latent perlode, and the eve re epidermal injury with minimal dermal injury. It is

possible that differences may in part be on BLL racial basis.

In addition, the marked dlfference in histologic response of tb epidemis and dermis in the present series is in marmd contrast to the usual radiation reeponse of the skin producsd by high energy X-or beta rays. In Table 3.3 am listed the approximate minimal surface akin doses required to prodwe recognltrrble epidermal injury in animals. It is anparant from the Table that beta ray energy la of considerable Importance in determining the degree of injury. A number of assumptions, inCludlng knowledge of the beta ray apectrum from the fallout, would have to ba made ff these data

were to be used to eStht6 biologically the bata dose received I by the IYlarshallese. The dwference in dose between that required to produce threshold skin damage ad that for pmnent damage in

I) Reported clinical experience with radiation skin lesions is based predoninently on the response of white-skin people, where- as tLe t;?h of' !.ez?mg described herein, with one clear cut ex- ception, were observed in Japanese, benhallene (negroid), aod American negroes. The exception was a dark brunette individual, pigs is 500 to 1000 rap (3,30). It fs impossible to estimate the probability of development of redlation cancer at the site of the healed leaiona. The ab- aence of scanlne, telangiectasis, end extensive chronic vascular lesions tends to improve the progncrie since "radiation cancern mparently develope in the scarred mees in which the blood SUPPLY is impaired. A favorable prognosis is also suggested by the following midencer an analysie of no0 individuals exposed to low voltage X-ray for dermatological conditions.rwealed no evldence of cencer induction 5 to 23 pears after treatment. LlaeKee (3.13) etatee thst epitheliomata rerev develop after a slngle dose of radietion to the skin. Iastly, the incidence of skin cancer in mgroes ia one sixth to om nlnm the incidence in Caucasians (3.33). Lf neoplesie can develop purely a8 the result of epidermal irraZiation, however, late cancers are obviously possible. Shee many children and pound adults were involved, the llfe ex- pcctancy of a large number of the exposed people will excwd the long Muction period for devebpnent of radiation cancer ob- served ln radiohgists. brig exposure to tropical sunlight, potentially carcimgemic in itself, may increase the probability of neoplastic change. The influence of the sublethal whole bow exposure received by these people on akh cancer induction is not known. The transverse band of pigmentation that was observed In the finger nails has been previously observed 'by Sutton (3.U) ina negress who received 150 r of soft x-rep to the bands. The nature of the pigment is not horn. Shce it occurred in ell -sed American negroes, many of the Edarshallese and mm of the American whites it is a radiation response peculiar to negrofd racea. The pigmentation VJ~S apparently produced by as little as 75 r of gama radiation since the American negroes developed the phe- wmxwn In the abesace of significant contaminstion of the hande. 3.8 Eoncluslons

Aa a result of this accident the following conclusions can be drawn -5th respect to beta drp;lage to the akin. a. Serious skin contamination of personnel from fallout may occur many miles fmm the detonation of a nuclear device. Re- sultant radiation damage to the skin L!% ;S xk m;or iadiatlon effect under conditions where early evacuation from the field 02 radiation reduces the whole bdy exposure.

c. Decontamination of the skin must be prompt to be effecti-c became of the Initial high bets dose rate.

d. A latent period of a fes days to 3 to 4 weeks mar elapse before SigM end spptomo of skh dmgu arc evident.

e. Clothing and/or any type of shelter gives almost complete pzotectfon to the skin.

86 3-L Renriques, J., J. Lab. bast., Vole 1, No. 28 153, 1952, 3.2. Glendenin, L. E., Nucbonics, Vol. 2, Uo. 18 12, 1948. 3'3. Harren, Shields, hh. of Path. 35r3C4, 1953. 3& Knoclton, N. P., Leifer, E., Aognese, T. R., Hempleman, L. KO, Bleney, L, F., Gill, D. C., Oaks, R. R., and Shafer, C. Le, J.X.K,A,, Vol. U1, No. 4: 239, 1949. 305 Payslrger, J., Plumlee, Ld. P., Sikes, D., viest, J. L., UT-AEC-1,. 3,6 Luahbaugh, C. E., Spalding, J. P., and Hale, D. Bo, Report on sheep losses adjecent to Nevada Proving Grounds, AEC report Jan. 6, 19.5ljc

3.7. Robhlns, L. L., Aub, 3. C., Cope, O., Cogan, D. G., langohr, J. LCi Cloud, R. PI., and Bierrill, 0. E., Radioloey 46:1, 1946,

3.& Crsv:for&, S., Arch. of Dennat. and Syph. 27:579, 1933. 3.5, tow-Bees, E.V.A., Radfologp 472213, 1946. 3.lQ Rlrth, J. E., and Raper, J. R., Eiologfcel effects of externel beta radiation, Zlrkle, R, E., Cbapter 12, McGmta-Hill Book Co., Xu., First Edltion, New rork, 1951. 3.1L hiorton, J. J., kiwis, J. J,, Shimomura, S., Fujii, T., Sears, Ll,, and Tsuchltori, H., Atomic Bomb Casualty Comisslon, Prellminnqr fieport, hrch 26, 19Z0 3-12 Morton, J. J., Levis, J. J., and Shimonura, S., Atomic Bomb Cssualty Commission, Supplementan Report, Apr. 19, 195&

3& &ache, G, M., CipOlhFJ, A. C,, end Montgomery, H. M., X-Pag and radiua treatment of diseaees of the skin, Fourth Editioc, Lea arid Feblger, Philadelphia, 1917.

81 0 3.11, illilhelmy, E., Strahlentherapie, 5514%~19%. 3.15 Harris, ffi-, kddy, E. T., and Sheard, C., Radiologg 19r233, 1932. 3.16, Balkin, Arch. of Dermat. and Syph., 651201, 1903,

3.17. Coldberg, London's, Das Radium, pg. 56, 1911.

3.18. Blom.. Vie, RXK~Bloom, Y. A., "adiation Biology, Hollander, Vol. I, Partfl, pg, 1119, McGraw-Hill Book Co., Inc., New York, 1954 3.19, iarren, Shields, Physio. Rev,, %:225, 19U. 3-20, Ngd!, F., Strahlentherapie, 9221576, 1953. 3.25 klbsch, S. KO, J. of Ked. Res., 16t415, 1909. 3-25 Raper, J. R., Zirkle, R, E., end Barnes, K, K., Atomic Energy Connission Report bWlC-439,

3.23. Snider, R. S., Histopethologg of' Irradiation, Bloom, Kap

First Edition, Chapter 4, IldCraw-Hill Book Co., Inc., Ne73 York,

19L8 '

3.24, Raper, J. R., Henshav, Po S., and Snider, R. S., Atonic Enereg Conmission Report MDDC-580.

3.25, Raper, J. R., and Barnes, U- Le, Bloloeical effects of external beta rsdiation, Zirkle, R. E,, Chapter 4, First Edition, Ne= York,

I 1951o

3.,26. Raper, J. K., Henslmn, Po S., 6nd Snider, R. S., Atoriic Energy Commission Report MDDC-578,

3.27. Henshaw, P. S., hider, R. S., and Riley, E. F., Radiology 52rLOl. 1949. 3.28. Lushbeugh, C. C., Stover, J. Bo, and Hale, D. B., Cancer, Pol. 6, No, 48 673, 19530 88 3.29. Trum, E. F., Personal communication of work in progress. 3.30. Moritz, A, Ro, and Henriques, F. W., J. Lab. mest., Val. 1, No, 2: 167, 1952. 3-31, Raper, J. R., Vdrth, J. E., and Barnes, IC. K., Biological effects of external beta rediation, Zkwe, R. E., Chapter 2, First Edition, Iiev Tork, 1951.

3.32. Sulzberpr, 1yI. B., Beer, R. L., and Bomta, A,, At.omic Energy Commission Report AECU-1616. 3c33. km, K. F., Illnecs from cancer In the United States, Public Eealth Report, Reprint No. 2537, Cwt. Printing Office, Jtn- 19U. 30u+.Sueeon, R. L., Jr., 2AoMeAa, Vol. 150, No, 3~ 210, 1952,

89 U 9 s0

m f 4 i '8 ! i Table 3.2 Lesions in Allbgnae and Rongarlk Croups

1 (28 M meof Lesion Per Cent of Total of Total with Lesions with lsaiolu I I Epilation 27 3.5- 42 I I

3809 26 10e7 32 ! j I El 00 27 u.3 30 ! 0.0 701 1 22.2 Y, 3e.5 23 I 11*1 28 2500 29 ! 506 s 3.5 47 16e7 33 3.5 43 i! I 5.6 w, 00 0

P I dI b2.l ! Iiscoloration 7707 LO i

m ~ Isotopcr

P32 .5 P32 05

PS e5 P32 -5 90 Sr e3

s35 0%

60 co 01

cs1n 02

Sr* 03

190 07

92 I Fig. 3.1 Conparlson of the incidewe a& tine cf appearance of epilation and neck lesions in the Rongelap and AlUngnae group

ll. I I 0 r 0 C

L %

ID\ I= :\ 3 J W \ 0 a z X 0 W K In m z 0 0 0 VI VI W t _I U 0 Y U W z

2

0m C0 C ? q 1 1 corn PLATES

Plates 3.1 to 3.17 Iagenla to be supplied by (;DFi B. A. Gonard

Plate 3.18 (XlOO. R&E) Epldermiaz Exteasitre tranaepldenml damage with less Involved zones on edther side. Loose lamhittion of strstum cornem, absence of stratum gmnilosm. Parakantirrination rith exfolfation of pigmeat ContrrFning aelle. Maorganlaation of the Ualpighlaa layer. Dermiar Mild dsma of para PapilLariS wlth iadi- stinct cepiUarS loops. Werately pronounced psrioaecuhr celldar infiltrate (lymphocytes and mononuclear phagocytes), in auperficitl

I corium slth mild tslonglectaals.

ZlEt@ 3-19 f XlM)). H&E ) Epidda: Arcades of dnirpal damage OCCUF in reltitlon to arcretory duck of areat glands. Stratum granulosvm of good rlda and ehws meant alteration. Underlying Stratm Wp5.gh::. ahas marked deerease in pigment. In the deeper portion of the over- ". 'I wmg, loosely laminatd stratum amem moderate mounts of pigment, however, are present. One mnvw arcade of more swmtrrs8epldsnd dssage shows alteration of the stratum granulosilm nith intcrroellular Bdv., pyknosis, swollen nueloi, Md pigment scattered throughout. Tho latter 1s especially dense in the contiguous parakeratoUc matoriol, Dermis: A moderate oellukv Infiltrate, chief& perl~aacuiar,ia

UOSt P~OrmCd the SUP8Z'fiChl mtiCdd8 Where them 18 a mud tslangiectaeis. Phtc 3- Case 6) Transepidermal damege rith disocgas&-

zation of the k'dpighian 4er. Stratum granulosum absent. ElalpighiU:

and basal layer only two to three cella thick W~thexfoliation of pig-

95 ment outward hmrd parakeratinlee3 none adjacent to stratun corneum. Pigment Wen chromatophores and histiocytes in pam papilkis of corium. Iatter is edemafoua and infiltrate3 by mcder- hte numbers of lymp\ocytes, mononuabar phakoums and mattered p.m.n. leukocytes. Capillar;y loope indistinct.

Plate 3.21 (X100. HLX) (Case Y62) Trsnsepidernal damsee with disc- ganimtion of the Glalpichian Wer. Slight parakeratosis. Lligratlon or exfoliation outwad of pipent. Loose lamlnatlon of stratum corneum. Pigment laden chromatophores and histiocytes in superficid pars papilbis of corium. bhrked cellular infiltration of pars pn?illaris. Slight telangiectasis of superficial pars reticularis. Plates 3.22 and 3.23 show lesions at 53 dws post exposure.

Tkte 7.22 (X103. H&E) (Case m) hose lamination of stratum cornem vdth oEtvrard papillary projections and resultant "rugose" cppema!me. Stratum gramlosum of gdwidth. Basal and Lldpighk.

le;rers distinct with piporit present. Slight edema of corium fi-pi-it\ nild telangiectasis and sUght increase in periv1%3cular lymphocytse and psricytes. Small, atrophic hair follicle adjacent to oebeceotiz g'd, - in mid pars reticubis, Plate 3.23 (XL00. Hi&) (Case ,9971) Sane as 3.22. OCcasioIlal peri- nuclecr cytoplasmic halos 5.n mid stratum grandosun. Loosdp lomln- atd strctum corneum, Pigment laden chromatophores in superficid corium &ing with occasional lymphocytes and nononuobar PhagaCytOs, Pkte 3-24 shows lesions (second biopsy) at 16 deys poet exposureo 96

Chapter IIT

1.1 atroducttppr Since it is generally agreed that a depression in the formed elements of the peripheral blood is the most useful practical clinicel Mex of the degree of exposure to ionizing radiation, a systemtic study of the leukocgtes and pletelete nas relied upon as a mjor ai5 In maluetfng the clinical status, 8Werity of the radiation injury, and prognosis of the exposed Individuals. Animal exnerimentation had previoualy shown that the rate of de- velopment and rnagnitlide of the depression were oqually important in evalusting the severity of radiation injury. Slnce there had been no previous exposure of human beings to significant arcounts of fall-out radiation, no hematological data known to be atriccly applicable* were available for use e8 e guide in the evaluation of the exposed Americans an4 brshanese. Accordingly emphasis was placed on systemtic serial studieo, utilizing c fen highly stand- ardized hemtologic detemlnations to insure tkt individual and group trenris would have meximum validity. Sincr: it we6 known that the Utirik group had received a very small dose of radiation compar- ed to the other exposure groups, less extensilve determinations wem camiei out on these people,

LD2 hm.1Uethob

Hematological exambations included toto1 le.&cyt.e, nsutmphile,

+ A large literature on the hematologic affects of radiation exiEts; however thsse date were not relied upon for direct comparison and evaluation of the exposed indiVidUah for rensons that will be indicet- ed later in the discussion, 98 lymphocyte and platelet counts, an2 hematocrit deterninetione.

Lhenevcr possible an entire exposure group was studied a

single day. Occasionally tm days were required to complete the

larger groups. Capillary blood wes used, usually obtained from the finfer but occasionally Ikon the heel or ear. Tm pipettes each for total

leukocfle and platelet counts were filled. From each pipette a

single hemocytometer chamber was filled. All pipettes were rotat- I ed for ten minutes, and the cells were allowed to settle for ten minutes in the hemocytometer chamber before counting. A three per

cent acetic acid diluting fluid was used for total leukocyte counts. Ths blood was diluted with 1 per cent anmnium oxalate for platelet counts and counted in flat bottom hemocytometer6 using a dark phase contrast microscope (4.1). Tno blood smears wera made with each

examinstion, using a 5eveled end glass alide for spreading. One

blood smear vias fixed In methyl alcohol. The other was staine5 by

Kright’s method, from which a 100 cell differential count was made.

&fiEtOCritS wez% perromed using heparinized capillerg tubes.

One end of the cepillarg tube vas heat sealed arid the tube was centrlfwed in an DEcentrifuge at 12,500 rpm for five minutes. Every effort was made to maintain unlfom procedures in every phase of the laboratory work. Tk number of personnel changes for

a given procedure was held to a minimum; persorrnel dravFng blood

from a skgle puncture were sufficient in number to allo7; all semplea samples to be taken in rapid succession, 811 timo intervals were rfgidlg controlled.

4.3 M"tho&3 of Trestiw Da ta. Control Grow Pre-exposure blood counts were not availabla on the exposed

Msrshallese or Bmericane; hence the MiVl&uals could not be used as their orm con%mls. In order to estimate the severifp of the hematslogic rss?cnse it was necessary to establish control groups as com-,arable a3 posGible in respect to Bee, mc6, sex, background, and habits.. A brshsllese control group livinp on Majuro, comparsblc with res~actto 696 and sex to the Flongelep people, was used e8 the Alarshallese control groupo For cornperison with the exposed Anericans, blood counts were mde on approximately 85 Anerican milles, on cluty at Kwajelah, All who had mt been on daty in the tropics for more than two months mere excluded since tho exposed Amaricam on Ronrerik h.d bean In the area fcr aboat two Itoaths be-. fore exposL-e. In addition several who were recrntly assochtei with radioestive moterials mere excluded. The rasultinz smnller pupof 67 was used as the Kwaj-Azzcrican control group, Preparatory to analy%ing the heastological results on tha ex- posed li:arsk-.llese, deta fmn the control 1kjmo Croup wore examined to determine if there was an age or sex deprdence in the hamatologic obsenztiors (Tabla L.1). Although the r~utroKhil9count was ln- dupelldcnt of a@, the lynphocyte counts nere sigr.ifican:ly high8r in ths youqer aga groups; however 6 relative deprecsion anpeared to OCCUT ot abut ago 15. The total leukocyte, neutrophils and lymphocyte counts were ic- dependent of sex. The hematocrit of fernalee WIX loner than that - of males, perticularly in the child beariq ape -wup. The age a?ld sex dependency of these endpoints is ccimperable to that in published data (L.2 and L.31.

To obtain valid comperisona within and amorg the various ex- poeure groups, they were stratified in accordance rnith age or sex dependency noted for the control pups. Althourh each individual in ell groups vias studied hematoloElcaUy, those Msrshallese with serious lorpstanding dlseeses were omitted from the analysis.

A total of two froln the Rangelap and two fron th+ bkjuro grouns vere or;.it-;ed on this basis. In the following descriptions and comparisons of the date., f’in3irgs ir the exposed groups am usually expressed in terms of per ceat of the approDtlste coztrol pup, It s5ou19 be note6, hovever, that fn observetioral stucliee of thia kW, unhom factors c.Juld poscib’l account for part of the differencss nz’teii betwean thc control ond exposure pcups wen though dl ?ossX3z measares viCi*E taken to select e comparable control groqC In adclition, it ms not pocsible to obtain more than a single blzod smple on each cozlrol inc‘ividuel, For theso reasonsp statietilel tesbs of slg- nificsncs vere appUec! maw to time changes nfthfr: afi e.xpos~?. group, 2x1 not to differences between control and exmsure grou?s.

For the purpose of detecting aignificant chacges IE the hemntolog- ies.1 pattern, nonparametric tests ii.e statistical tssts for viiiich iC 5s not cscessnry to specify the functional cXstr.ib.!ttion of the vmiete uder s‘;udy) were used h.L to 1.9). The advantapes of ronperemctric msthods hsse been smarized (L.10)

Let, ~~~lc~ic~lFUe3. Gens? Totel lcukocyte, neutrophile, lpiphocfle, mmocyte, platelet and eosinophils counte for the several exposure proups are given by dry end hy are in Tables 4.2 to 1.5. The mean Gotel ahits count, rcztro?hile, lymphocyte an3 ?latolet counts at Lhu tbes of pmk c'epressien (t.lme over which counts viere consistont3y the lone,rL) sra shorn in TEbles 4.6 and 4-7 for each 17divlrl;uIl in the kngelap ecd Ailirgnac POUPS, respeatively. HeiatologiCal fhCiqE es a fumtion of tb.e end age ore chon olso in Figurss 4.,1to L.E,

The cumdative 2istribution cwos for %he varioas oxposure mupsI usiy the avertre of counts obtoined over the norkc of morinun depressicn (Lap 3'? to 51 fsr leukocyto.3; days 25 to 30 for p:atr.- lets) CITE shcm in Figures 4.9 to LVlL* In tho fiplres enDh::s:.s is ?laced on the individuel blood elements rathtir thrn on the tot.~l 1eubc;ste comt, since the compcnent elelrents ham dLstinct and different tine trend6 after irradistion,,

4.5 ROnmhK Group

Tie absc1u.t.e neutx;lhfle comt of both ths yowqsr cxd oXen sgs poiq.8 fell durin- the secofit week zo 3 veliw, nyroxiaatc2.j

7'0 tc 8Q.psr cer't of th2t of the coctrols (see Fig. 1..1). Fo2mc ing the Le?resslon of the ,total neuzmphlls coruit dwicy the seccn'. week, ::IF vsluc8s were ,anstable uritil thi? fifth w3~ek.. At thio tim? the boCiFn- cf 6 secona drop (P< 0.01) was noted for both a@ --* Ir- ths Utirik coup the cumuktive dktzibilt:lon clime for platel;. ec!mts ora 1s presont.3d since hemtological ddi~m~~ationsin tk& E;roup were not mode ami%: the ?9 to 51 dazr 93ri.32, used for leukxy:.,: cmjxrisons ancnc the other groups.

102 paps, and a 107 vFlue of a~pmxlmately50 per cent of controls

W'IC reachad. The count was maintained at approximately 75 per c3i3 of control values from the 7th week to the end of the study. Although both age groups followed the eame general time uattern

of response, the lower age group was belopt that of the older scup throughout most of the obseruation period.

The absolute lpphocyte count of the older age pup (Fig.

I 1-2) had fallen by the third day to a value approximately 55 per cect of the control group. This value was maintained throy.hoilt thc study, and there ma no definite evidence of an upward trend durfng the study. The values for the power age group likewise fell befo:e the third day to a value approximately 25 per cent of the aontrol, folloving which there was a significant upward trend. i';t,th the total lsmphocfls count, there le a consistent difference bntneen the two age groups. However, durine the first four w8eka

thc difference ia accentuated then expressed a8 per cent decressa

bucause of the relatively high lymphocyte levels in the lower age oootrol group. After this period the differences expressed as per cent me less marked since recovery v&s more rapid in the younger ape group. The cellular elements chiefly m6ponsible for the fluctuakions in total nhite blood cell count can be determined by cornporing the total nhite, neutrophile and lymphocyte counts (Pip. L.3). It is soen that the lymphocyte count remained eaaentially constant through-

out the period of study, while the total neutrophile count fluctuat-

ecl with a pattern essentially identical to thot of thg total white bZood court (coefficient of correlation of 0.9). 7 n.r -Y tiom in total count were due to chegee In the neutrophile count.

This BYE true of both the older and younger age groups. It can be seen froa Table 1.2 that the neutrophue count ms conslstent- ly greater than the 'lymphocyte count In the older age group. In the younger mups, differences in the neutrophile and lpnphocyte count nere less marked and on sLr oceaslona the lymphocyte count was greater than the neutrophile count. Plptelets were first counted 10 deya after exposure, at which time platelet volues of the older age group were aproxt2letely 70 per cent of the control pup fFQ. 1.1). Followlnp this, the platelet count fell reach- a low of approximately 35 per cant of control velue duriq the 4th week. T!I~platelet count rose during the 5th week and reached the value noted for the initial oounts 03 the 10th day. A second decrease ln the platelet count (P 0.01) developed durlng the 7th end 8th weeks, and values remalned at epproxhtely 70 per cent of the control group during the remainder of the ovservntion pari&. The pattern of platelet counts in the below 15-year group was remarkably similar to that noted in the older age ~ups.Dmerances between &!-.e age groups wera less apparent lf the platelet counts were expressed a8 per cent of the contmp group. L.6 wseGroyp

In this group there were only three Mividuals below age five. For this reason, rem.rke will be confined esaentially to tne oXer ace pup. The abeolute neutmphlle count fluotuated around the control value for the first 6 week8 of obaervatfon (Tahle 1.3). At this time the counts began to fall, aol a value approximate4 75 per cent of the control count was reached and mrrintaW thmughout the duration of the observation period. The lymphooytee in this group fell to a value of 55 per cent of normal during the first mek. The counts then fluutuated around this value throughout the period of observatlon, and no definite upward trend of the lymphocyte aount was noted during the period of observetion. & was noted in the Ron&ap group the lymphoqde counts re- mained at an essentially constant low level throughout the period of observation. The total leukocyte count in this group also ro- fleeted changes in the neutrophile oount. The pletelet counts in the Aill.ngnae group were low, approxi- mately 75 per cent of norroal, when first enumerated on post-exposure day 10. The oounts remained at this &vel during the aecond ad third week, however, a definite fall in count was noted durFng the fourth week when a low value 15 per cent of control was attained.

The counts returned during the flfth week to a oglue apgroxhtely 70 per cent of the control level, where they remeined for the dura- tion of the observation period. A secondery fall, as observed the bngelap group was not detected. 1.7 !&- In the greater than 5 age group the total white bhd cell and neutrophile counts were depreseed slightly below control values dur- ing the first and second weeke (Table 1.4). The lymphoogte counts were blow control levels wnsistently, end tho total white count equal to the control value obtained on day 29 was due to a neutro- philic leukocgtosis. Platelet counts on the 29th day were significantly lower than on the 19th day and were lower than aontrolvaluea. The 29th day coincides with the timd of maximum depmEEbn for the more heavily awoaed groups. 4.8 Ronrrerik WM(h e The neutrophile count in general reflected the time course of the total leukocyte count (Fig. 4.5). lleutrophllerr accounted al- most entirely for the marked rise in total count on post-exposum day one, and the values for absolute neutrophile count fluctuated near the control values thereafter in the course of the study. The lymphocJrte counts fell to belon control level6 in the first few days, and remained et a level eprroxhtely 75 per cent of the control velue throughout met of ths remainder of tb observa- tton period.

Jn the Rongelap and Alliagnae groups the fluctuations in the total leukocyte count were scoounted for ahst entirely by changes in the total neutrophile oount. The Rongerik group dfffered since the changes in total 1eUkDcyte count were reflected almost equally in the lymphocyte and neutrophil6 oount. The signLflcanae of thio dlXference in response in the two groups is not apparent. The platelet counts F&. 4.6 were not markedly depressed when the initial counte were taken durirg the tbM week. At the end of the thM week, however, the platelet count began to fall to reach a low of epproxlntataly 60 per cent of control levels at the end of the foltrth week. The value then returned to approximately the control level at the atart of the seventh week, following which a second depression wa6 noted. The platelet oounts were at a level of 80 per cent of the control value at the time of tbe last observa- tion dura the elghth post4rpostos reekk. 4.9 4g~pcfiesand Eosinp&&les. All hma From Tabla 4.2 it 1s 8een that the mean monocyte count for the Rongelap group rose abruptly from an earb value below control levels to P well defined peak on day 12, following which It f'luctust- ed at value6 bolo= the control he1for the duration of the obsema- tion period. A sLmFler the tred warn noted in the U1-e ad Utlrik groups. The eosinophile count in the older age indlvkluals, Ror@ap group, K)68 from very low levels observed on day 3 to values ap- prodmating 35 par aent of control during the eecood week, where it renriwd from the third to the fifth week (Fig. 4.7). The counts then decreased (PC 0.01), and remabed at a value approximately 15 per oent of oontrol throughbut the -Mer of the study. The t- trend of response ma rhmilar In the yourrger age krdividaalsp however changes in the younger age group were mlatlvely pester lf coneidend in terms of the control values. Similar trends in eoelnophlle count were not evldent ln other exposure groupsG It Is possible that the rise in eoslmphlles represents that reported a8 occurring " two to three weeks after short-

107 The hemetwrit values for all exposed groups are ahown in Tabla 4.8 and 3n Fig. 1.8 (a detailed breakdown of hematocrit by age and sex for control groups ia given in Table 4.1)- Khan hematocrits were first done on the 22xd day, mean value8 for the Rongelap and Ailingnae groups were blow those of the control pap- ulation. A slgnlficant trend fn values after thin time could not be detected statistically.

4.11 Of PeriDha Blood Significant morphological cellular changecr, with the SxFeption of a smell number of abmlmnonucle~r COW seen in a nmber of individuals during the period of neutropenia, ware not observed, Sbllarly altered cella have been observed prsvioualy (5.U). Dom- plete evaluation of these ahsnges in the present study would necea- sitate an exhaustive serlal study of the hematology elides. 4.12 wiaonof ma- F in fill- Adults,

It- is seen from Tables 4.2 to 4.4 and Pigums 4-1, 4.2 and 4.4 that dlfferencea la the degree of dspresaion of cellular ele- mento were present between children and adults. In Table 4.9, the mean values of the neutrophile, lymphocyte and platelet count8 at * There ma considerable difference in opMon in respect to claesefication of these oells. They nere classffied as &yplcal mon~cptes,degeneretiag lymphocytes, atypical ~~locgtes,~oaocytoid l:phr?ytss, end lgnphoc.p,es ir trpnsition to znyelocytes. At $he tins of this report there wee no unenimity of opinion iil respect to classfficafion and significance of these celle.

106 time of peak doproasion for each element are given In terms of absolute count and per cent of approprlatr control vnlur (mitan platelet aounts were aaluulatad for the lose than 5 and meter than 5 age pwpe for thfe comparison). It is seen that in terms of abeolutr counts, the children

showed B greater depression of the osutraphlle couat, and the B~IW degree of depreeslon of the platelet counts and lees depression of the lgmphocytr count. These differences can be most easily doecrib- ed at the time of peak depression. Expreaaed an per cent of control., all elements wm affected wre markedly in the younger age group, These results would iadlcete that children are more sensitive to I- raclbitlon, 0; that other biologkal or p-lcal faotors redtad In a relatively greater effect.

I 4.13 4.1301 An estimation of the swerity of radiatien dsmage burred can be attempted by comparing the pmaent results with previous hematological &ta on total body exposure. The present data re- present tha onl~large series in which systema'cia smhl counta on the same Mivlduals have been possible, and thus they comprise the most complete data available on human beings exposed in the high clublethal range, It is alea if importame, therefore, to eraaka the present results in conjuaetion with past experisnee in en effort to pin a bettor ucuieretanding of the bematologieal re- sponse of human beings expoeed to penetrating radiation in the sub- lethal range. In the fallowing discussinn it will be generaZly aaeumel. that the bemetological effects smted =re due primatug. to tb penetrating gamma radiation mcelved. The beta radiation injury of the skin mag have contributed to fluctuations in the white count during the period of active lesions durlng the third, fourth and / fifth week, but fs considered not to have contributed sigalflcent- ly to depression of any peripheral elements (see Chapter 3). Tho degree of internal oontamination with fission products (see Chapter 5) was probably too smell to contribute eignirlaantly to the ear* hematological effects obsemed. Althoagb it Is not possible to s4v with oertahtty thet these added factors did not materially af- fect the hematologioal pattern aeen, it will becom evident in the discusalon that the ch-s observed are not firaomistent nith

those to be expeated Prom e%poaure to penetratiug radiation R~ODEI~

Thus the bematelogioal ahangee mtsd BCB aonaidsmd to bc the re- sult of a single exp8ure to penetrating gamma radbtion, deliver- e3 at rapldly decreasing dose rate omr a period of approximetsly i two daye. Unless othenrlee stated all discussion will t~ limited to the older Rongelep grolrp. The principle eouraes of previous data availnble for couqariaon, 4 the cbaracterlstlcs and limitations of each are sunmarheed in Table L.10. Perusal of the table wlllmake apparont the dLfficultles involved in attempting strict comparisons; however sow) statewintie can be made despite the obvious limitations. For easy reference,

110 wrrormelwvaluee for peripheral blood counts, from the present dab and from the literature am presentmi in Table 4.11, 4.13.2 rith the 2- The limitations stated in Table 4.10 app9 to the Japanese low dose groups* E to E in particular, in which value8 given (L112,4J3) are pooled and blde individuals looatad at the time of the bomb- ing such that they may not have received signfflcent exposum.

Bence, while the pattern of chmge with rarrpect to tiar, is of value, absolute counts probably are Ugh. The tM course of hem- tological change in the Rongelap people eomsponded mast close73 with these lor caposurs Japanese groups in which defidte sign8 of amem radiation expsure pmsent in oome indi~idualsbut In which essentieq IY, mrtality occumad (inltlal hematological stdies on tha Japanass terminated at 15 mka). ehe early period up to apurox5mately 6 weeke was characterised by coneiderabla varis- tion in total white aount ln both the Romplap end Japaasae people, Thio fluctuation my be associated nlth the presence of thermal or other Injuries in the r'apanese or the ective skln lesions ln tha Plarshallese, or may comspond to the "ebortlv0 rise" noted for anhnls fo?.lomhg exposure (4.17, 1.20. Fmm tb sLxth week until the torminetion of the acute studies on the hrshallese during tbs tenth seek; the Japanese and Karshallese counts remalned at shllar levels. * The Japanese casualties were divided into groups A to H on the of degrae of exposure aa determined roughly by distance from the hypocantor and approximate degree of shielding. In groups E to H essentially m mrtrrlttp aaorlbable to radiation exposum occurred ia the fbt3 or 4 monthsD TbO KmUtrOphilo count h both tb0 hp8mBO and MarShalleW in general paralleled the total white count. The mivcyta count

both -Up8 Was depressed early ad remained depr8ssed at values or approainately moo until week ten. ma high vah of 2692 reported for the Japanese for weeks l2 to 15 mutt be suspect- ed of be- high for the reasons given in section 4.13.2. Three characteristbos of the Japanese imsnatologlcal trends

&odd be p0- Out: a) Whlh high dose O~pDElrrt,g”OUp8 With slgnlficant mortality shad ear9 deprseslon with a definite la. point at 4 weeks, tbe lower dose groups @&wed 1y) defia2te midmum ut 4 week8 but rather a aontlnued depression until the 8th or 9th reeks. b) While the mean T~UB for total white and neutrophtlo counts for even the he~~iry groaps hed reteto within the anormala &age for iodivldual counts by 8th cr 9th weak, neither of these values for either the high or low expo6ure groups had returned to the meen levels of aqy of the control populatione llsted in Table L.11 st this time, nor the end of the study at

1s weeks, e) Lynphocyte count8 Femained depressed at least through the 12th week and probably through the 15th week. present fbdings in the Marehsllsse are in accord with theae oharactaistics, nams~a) totd white ceU and neutrophile wmts showed ID definite minimrrm at 4 weeks as evidenced In

t bunt6 2 year2 hter were not significantly different Ram control Japanese Talws (SelS)e Japanese groups A to 0, but rather fluctusted during the first few weeks with mininnrm mean counts occurring in the sixth week or bter. b) Neutrophile oounts were nnstable over the first 5 web, and recovery to control levels was aat complete by the 10th' week. c) Lympb@e aormtti nmainad dopremed thmughaut the period of obamation*+* Platelot data in the Japanese are not sufflaiCmt to allm aop8 thaa rough qualitstive comparleons. This la unfortunate ainoe changes in platelet aounts in tbpmsent studies appeared to shew a more oonsistenf pattern fhan did the Leukocyte counts. Platelet counts on om fbllvfduel considered as atypical response in a non fatal Japanese (4.13) Micatad an appmt low et ap pr&mately day 30. This tlw trend agrees wlth that seen in the Karahallese and AmerZcana -sed b fallat radiationo It is wortby of note the period of peak incidenoe of purpura in the Sapanese victims occurred betman the 25Zh and 30th day, which ccrreapords to the tlm of mMimum platelet depression In the exposed Mamhallese. 4013.4 on with Data irom laborstorp k&W!?& Al%houghin the Loa 81.moa 8ad Argotme accidents b.15, 4J6) the type of radiation and the corditions of exporrure were markedly different from either th. Japanese or the Rongolap altuations, a

(w Counts oh the Rongelap people 6 months sftor erposure showed no elevation of the mean total white count, neutrophile or lympho- cyte count8 over values obtained during the 10th weeke lege component of penetrating gemme radkntion was received ad thua attempts at comparison may be of value. Some fieahga in the hematological response6 are pointed out: a) a udf.~lrearly rise in white and neutrophile eounts wer the firat fer dares sinllar to that seen early in the Rongerlk Bmarican gmup me ob- * eemed Unif0rm5J.y~ b) Of three bat non lethal Czsea, the total white eod leulmoyte counts contirmed to show so= doqee of depression into the 7th wek or bepnd. c) The lynpho- cyte counts in Mividuala axposed to as little as 50 rem showed an lnitialmarked depression. In most cases the Qmphocyte counts remained at low levels throughout the period of' obaervathn. d) Platelet counta were done by a different method, and abeolute counts are therefore mt aolaparable. However, of the three high- dose sur?lto~,times of ~~m depressicn were mt Lrwnsietant with the value of 30 dcqm obtained in the present etudi6tb The lrgonne Iaboratoq accident Gb.16) blved four individuals who wera estimated to have reoeived 136, 127, 60 and 9 rep, reapact- ively. The findings in the two highest exposed lndivlduals in general mre oonsietenf with those in the present study, dn initla1 nautrophilic leuk~cytoeisme followed by fluot9mtloxw in total count, with lor values continuiag into the awenth week. Rscoverg was not complete by the tmntieth week. The lppbeyte aouut de- prosaion was rapid and ma~ked, and recwexy was not evident w tho

Bo Counts were taken on the Rongelap and Allingnse groups during this early periodo lJ4 tnentleth week. Mlnlmm values for the plntebt count were obtainsd between the 25th and 3lst day. 4.13.5 Tha time mnda ald ruverlty of peripharal blood oormt chaw following total body redlation in animals has boa critically ex- mlmd recently (4.17), and the fO&Rhg gedoonc~wions are presented . a) An initial rim in total uhlte couut (refhtd in the neutrophile couut) amy OOCUT. Themafter fhs .agaittdb of depres- sion of the total white and neutrophils 001111ts, and Rlthin limits their duration IUW a function of radiation doset A sacodary or abortive riso in tho total white count (Mlected in the neutrophile or Qmpho- count) may occur, followed by a amnd decrease. There is Utle speclee differems in the rate of dqmsslon of the total whtte or MUtmphlh count at oompatabl. doses; bDlnrvar the rete of recwery and time for complete recwery is quite dif- ferent in var~~uaviea. small animals (mow, rat, -tor) &OR relatively complete recovery to control levels, even at dows in the lethal range, by the end of the fifth week or earlier. Data on dogs ata badequate to indicate when recovery is complete; how- ever return to control lsvels at high dose levels has mt occurred by the fifth week. Swa!.! require &e to fifteen or more weeks for complete recovery. b) Ths mapme of lympbcytas is essentially identical In all animal species. Depression cap be detecfed within a fen hours, ard rSC0~l-yhpm the minlmumr values (acueved in 36 to 48 hours) re- us quires longer than doer neutrophile recway. -0s fall to very low levels at doses nsllbelow the lethal range, Md increas-

ing dose results in no or minim1 Rpthar doaream in count. Lymphocyte depression appsars to have no MUS^^ rslatiozahip with acute cadiatfon deaths.

c) Platelet counts have been studied nost extensivelg in dogs (4.21). Aa with neutmphlles, the rapiaity and magnitude of 'I depression is a function of dose below the lethal range. Lhxlmwn depreeeion occur8 by the 9th or 10th day with doses in the high lethal range, by the 10th to 15th day at sublethal levels. Re- oovory begine during the 3rd week, but is not complete by the 30th day vhen most studios have teen termlnsted. heufficient data are available to Micate the tinm requlred for complete ncovery. Considwable evidenoe lnclud4bg studies In the mouse wing splelfc homogesnates, induced bacterial fnectiona and rpontaacous infections have indicated thet critical neutmphlle~levels exlst below which smival is correlated with the absolute neutrophile count following whole body kradletion. From data an dogrr, it ap- peers that survival ie likely unless neutrophile counts remab be- low 1200 cella for a period of time. Platelet &ta on dogs irdlcate that aniraels with externel purpura have platelet counts of 50,000 or below. Insufficient data on large anhls are not as yet avaihble

to quantify the extent of makhm depression of either the mutm- phlle or platelet counts as a ftmation of dose in the sublethal range. The response of the platelet count ln the present study was much less 8ubjeot to fluctuation than rem the neutrophile or lymphocyte oouuts. For the podding xwmo~,myutmmtic hesti- gation of the platelet and le-e counts in large animals as a function of dose in the sulhthelrsngs are indloated. It is not possible to aey at present whether emerity of ex- posure, cr of radiation damega oorrektes better with absolute levels of peripheral blood count, or with degree of change from oontrol or pza-erpcsure lcnrelct. Some evidence on this point can be gained by comparing the de- of depression of the mutrophlle and platelet counts in the Aillngrme .Id Rongerlk groups, both of I whioh had essentially the same calculated axposure but for which

control hematological values wpo considerably different (the

'I lymphocyte count is not suitable for comparison since degree of

depression was essentially the same in these groups and tbe higher- dose Rongelap pup). At the time of peak depression for each ele- ment, both the neutrophile and platelet oowt6 were essentially ldentlcel in terms of absolute counts, but conalderably different !I.,. in terms of the respective contcolraluea. Thus 8me ev,vidence is aiforded that absolute counts, rather than counts relative to control values, may be thr more reliable index of expoaura in this dose rango.

4013.6 &PKiXimatl on of IG1n-l Letha 1 epke for Soma indication of severity of exposure can be gleaned from e caparison of minimum individual counts in Japanese pups ia which fatalitlea occurred. In general, significant number of deaths was encountered only in MivlduaL whom neutrophile count fell below 1OOO. In the Bongeltip group 12 or appro&tely 50 per cent had neutrophile counts blow 2000 at some time during

the observation period, and 10 per aent hd COUU~Ebelow 1OOO. By this criterion, then, the eSfective dose received by the Ronplap

pe0pI.e approached the lethal range.

Ia the dog and mouse (4.22), appmtlmately 50 to 100 r am required to lower the neutrophile count by loo0 cel18/min3 in the

I! high sub-lethal dose range. If these data can be applied to man, an additional 50 to 100 r would have placed the dose well in the t lethal range. On the other had, horwer, it la ole- from the . present data that nsutmphlle cormts between loo0 end 2000 in human beings are well tolerated. hanbeings with these levels of mutro- phFles show no clMcal widence of illness, are physically active, and do not need prophylectic antibiotic therapy.

The Rongelap people ere sstfmated to have received 175 ras

calculated from dose rate madings measured ln air in the plane

Y fission product field. FMm the preceding paragraph it ie seen ,I... .. , that an additional 50 to 100 r of laboratory radletion or an average of 75 r, probably would have resulted ln sone mortality. Correct- * ing this average value geometry, it follows that the minimal lethal

From geometric and depth dose considerations set forth In Chapter I, 1Wenteen measured in air in a fission product fleld is equivalent in it6 effect on man to approxiroately 1-5 Roentgens of penetrating x-or gam radiation tuirlsr geometric corditions usually used in the laboratory. Thus the blLD for man exposed to penetrating radiation derthe usual Isbratory conditions mula be approximately 335 re ll8 dose (ELD) for map exposed fn a fission product field is approx- htely 225 r measured in air. It is possible also to estlmate the added inorement of dose that would hve resulted in soma mortality among tho Raagelap people from oonslderation of the minumum platelet counts observed, the platelet lwele h dogs exposed in the high eubletbal range (4.21), and the estimeted rate of decrease of plstelet Iwel with Inereas- in& dose in thia dosage raw. Such an analysis leads to the aw conclusions as those derived from neutrophile data. 1.13.7 Perimberal Cowan Index of Severltv of Exmsm*, The relative valua of the stweral hematological determinations in estimating ths degree of exposure, as well as the approLinate dose rawee over which marhum sensitivity for each dstermiaatlon exists, can be estimated by comparing the degree of hematological

'I Tables 1.2 to l.5 and Figures 409 to 4.11. Lgmphocyte counts 1ow depresaed appreciably even in the lo*-exposure Utlrik group. In tha

higher dose groups, however, with widely dmerent physlcal estimates

of exposure the lymphocyte counts showed essentially Identfcel degrese

.:I I of depression, The lymphocyte count6 of the bngelap and dillngnec

pups were constantly depressed at e level of approxlmatsly 2000 cells, Thus while sensitive at very low doses, this endpoint msy be a poor index of the degree of exp~suraat higher doses. The tote1 neutrophile count of the RongeZap group was consistently mom depwssed than was that of the sUingnee group and the dLeferenco sa of the order of 500 to loo0 cells. However, day to day ride fluctuations in fhe MUtMphih counts occurred. Accordingly ll9 thfcs ervlpoint appeared to bn of limited usefulness as an Mex Of relative exposure severity except when counts on groups to be com- pared are performed at the sam t5m. The platelet count showed a mom sgsfematic trend than did the neutrophile count. Differences between the lowdose Dtirik pup and controls at the time of maximum depression for all groups uould be detected, and appreciable diffemnoes exist& btneen the means for the Marshalese higher exposure groups. Platelet countfng is an easy as, and mors reproducible than leukocyte counts k.1, L.23). Thus the platelet count may prove to be a useful. lndex of degree of

exposure throughout the sublethal WE^. The above considerations are in accord with previoua flndiugs on huroan beings aad animals. 4.3.8 jhncluaioqk

1. Consideration of the degree of depression of peripheml ceilular elements indicates that exposure of these Pmngelap people

WBR modoretely severe, pzpbably with& 57 and at most 100 r of the levo1 ehere some fatalities would have resulted. 2. The degrea of effect evidenced in the Rorgelap people is

not huousistent with the pkvaicalerrtimates of gamma doe% received,

Beta leoions of the skin, and the low levels of internel radioactive contamination observed are considered not to hove mwtributed s&- nigicantlg to the hemtological changes seen. 3. The extensive serial hematological data obtalned, consider86 In cor.nection with prwfous data, allow reaaonsbiy accurate charactsr-

120 leotion of the henastological Fesponae of human beings exposed to single doses of penetrating radiation in the high sublethal range. Ths time course of events Is differant fcom that observed In large animals and may be described as folhwar

a) The total white count masee during the first 2 or more days en? then decreases below nom1 levele. The total comt than fluctuates over the nest 5 or 6 weeks, with no definite minfn\ns and with aome valuea above normal (the presellce of them1 or beta lesions, or other acute proceasea during this time may account in part for these flwtuationa), Ths oount becomes atabfflsed dur- lrq the 7th or Bth weka at low lmls, and mlniuiua eowits probably ociur at this time. A definite tread upward is apparent in tho ninth or tenth weeks; howmar complete recovery may requira several mostha or momo b) The mutroptl3.e count prallels the total white blood cell comf, Complete mturn to normal values does not occw for several months cw more. The initial rise in total white count is due to e aeutrophilic leukocytcsis. c) Tim drop in lpphacytes is early and pmfound. No fmLdeaca of rocovsry may be apparent several montRs after expwre, end re- turn to normal lwels may riot occm for months or paars.

d) The platelet count, unlike the fluotue’cing total leukocyte co-mk, falla In a re-r fashion and reaches B low on the 30th dap. Some rscovury is evident early; howwer as with the other ele- ments, recovery may not be complete several months after expos~we. 4<, Aa an index of sevority of exposure, perticularly in tho sublethal range, the total white or neutrophile counts are of limit- e6 usefulness because of wide fluctuations and because several waeh-s my be required for meximm depression to become evident. 'Pas lynphacyto count is of mom value in thls regard particularly in

the 10V do66 rang0, 6bC6 68pTES6iOn OCCulB Within h0WS Of 9%- pcsure, Bowever, since a mrhd depression of lymphocyte counts occurs Kith low doses and ehe further increasr In dose producea little more c!fiI:rassxmn, this index is of 1f.ttle value at the - higher doess. 5& Platelet aountc showed a regular pattern of change in ths pms3nt stu-lles, with the same time of maximum tepreesion In all exposure groups and wit!- the degree of deprossion mug id^ pro- prrtiollal to the calculotud doses. It appears, thsrefom that thf pktelot cow% has consrdereble promise In the Fublethtl range e3 a comnienr: end relntiveu easy direat method of daterminbe ths dcgrae of exposureo 4,l Brecher, C. and Cmnkfte, E. P., Journal of AppUed Pbpiologp, 3x365, 1950, 4.2 Nintmbe, M. E., Clinical Hematology, Lea ~ndFeblger, Phil. 19510 4=3 Standard values in Blood, Air Force Technical Report No. 6C39, 1951. 4.4 Fklah, J. E. "Applications of some significance teste for tbc nteSisn which are valid under very genom1 condltdonrs," Jour. Amen, Stet. Assoc., Sept. Vol. 4.4 (1949), pp X2-355. I' 4.5 Boaenbarn, S. "Tables for a nonparametric tes: of locstion," Anmls of &th. Stat,, Illerch, V u4* 25 (1954) pp U6.-1500

406 Rosenbam, S. PTablea for E nonparnmctric tsst of dlspe?.slonpu

h753 of hkth. Stat., December, Vol. 2t (1953) pp 663-668. L.9 Dhn, K. J. "The statistical sign test," 5our. her. Stat, kssoc., December Vol. 41, (1346) pp 557-586. 4.8 Quernuille, &loE. Chapter 3, #Ordering Tent,R kcsdenilc Press In$.* Publishers, Ner: Pork, 1952, &o.9 ikite, C., "The use of ranks Ln e teat of sf&ficance :or coaparing two treetnsnteam Biometrics, 8, 33 (19421. Lo1O E.oms, Lo X., Nonparamat~'lc statistics for psychological

IWSSCLTC~, Ps@. Bull. 49tU.2, Mh19520 4.11 Zinot, 0. R. and Skurling, Re G,, The offect oil the blood of irradbtfen, esgeclally s~kcrtwave length Rcontgen Ray Thempy, km. J. Ped'; Scl. 168~215,1924-

I23 4.12 Oughtereon, A. E., Leroy, G. V., Liebo~, A, A., Hemmond, E. C., Barrett, E. L., Rosenbaum, J. D. and Sohnelder, B. A. Medical ef- fects of atomic bombs. The Report of the Joint (;ommission for fhs hestlgation of the Effeate of the Atomic Bomb in Japan. Vola, 111 and V. Atomic Energy Commlsslon Documents, Ap3038 and NP30,$0, 19% L.13 LaRoy, C. V. Hematology of Atomic Bomb Casualties. Arch. 5% Med. 861691, 1950. 4.14 Dunlap, C. E., 111. Effects of midistion on the blood and hematopoietic ti66WSs sn~l~aiagthe spisen, tb tm and ths mhnodes, in Ramen, 5: Effects of radiation on narmal tissues. Arch. Path. 318562, 19#. LOlS hpalmem, L, Ii., Lisco, E, and Hoffman, J. G. The acute radiation ayndromex P study of nine cams a& e. mien of the probhr,,.. Ann. fnt. Ued. 361279, 1952. 4.i6 Hasterlik, R. J. ClMoal report of four indivlduala accldsnt-- 4 exposed to gamma radistion a& neutrons. Ar@nno Natloanel kbr- atory, Jan. 1953. 4.17 %onkite, E. P, The Protective effeot of grwulocy-bes in radiation fnjtxye To be pu511ahedo 4.18 Smll, Fred Eo and Neal, Jam36 V. &matoloopic studies in Hiroshium and a control city two years after the atomic bombing. Arch. Int. Ned. R&:569, 1x9. 4.19 Pmasolva, P. 3emtologic studies of irradiated sumhra in Hiroshima, Japan. kch. kit, 6M. 911310, 1953. L. O., E. R. Uka and E. hen%. Kecmtologicsl effects of lonleing radiations, Radiology 52x373, 1949, 4.21 Cronkite, Eo P, and C, &ocher. Defects in hemostasis pro- duced by whole body irradiation. Josiah &cy. Jr. Foundation, Transactions of the fifth conference on blood coagulation, leu. Pork, 1952, 4-22 Certer, R. E., Cronkite, E. P. ad Bond, V. P. Urpublluhed I dats 4.23 Erechar, G., Schneiderman, B. S. and Cronkite, E. P. 1 Tb reproducibility aud constancy of the platelet count. Am. J, i Cline Path. 23:15, 19590 Table 4.1 Barnablogical Rsanlta, Control Omups

22 13.2 4.8 7.4

U 10,6 4.8 5 61

63 9.4 4.8 4.0

L4 9.6 5.0 3.7

m 9.7 4.8 1.1 9 - - 76 - ..

28 7.8 4.1 3-1 23.8 4,c9

I- * I Numbers in parentheses indicate number of individuals in the grout

!. .

110 2870 155 2770 115 2570 105 3350 US 3070 85 2670 195 &lo0 95 2600 85 1670 80 2520 u5 2620 105 2520 ll5 z20

3520 I 5020 5620 a20 5100 5120 4720 7220 5600 5120 am 42m 5750

6420 ,130 2650 255 5220 195 2520 252 5470 125 2700 2.42 4550 1C5 2770 157 3120 85 1570 135 4670 150 3270 127 4050 105 2370 152 4570 55 2770 170 CaSe h'De

18 22 25 27 9 34 n 40 4s 119 52 55 56 57 53 63 62 63 6.4 65 GS 71 73 74 73 73 a3 82

132 Table 4.7 hII;IN;NAE GROW MUN BLOOD COUNIS AT TDKE OF PEAE -IDN

Age use Than 5

6 9750 215 3470 56m 8 a350 185 3520 1350 44 4570 180 2350 m3

43 4220 53 6170 81 4700

Age Greator Than 15 1 6170 175 16 4670 195 28 6270 ll5 29 6750 w 3l 5650 u5 4l 5120 UO t3._ 6150 a5 45 5650 280 50 7050 95 51 7-750 170 59 12100 Io5 73 5070 165

135

'IE; Table 4.U Mean Perlpherel Blood Count Values for eevsrnl Coatma?. Popdatione (x 10.7)

Ameriaslls 19.47-194e 1948-1949 (4.2) .(4.18D _c1.191 9.9 9.5 7.0 5.5 5.0 403 2.9 2.8 2.1 006 006 Oeb

0,9 lo0 0.2

s 0.31 0.0 - - 29**

.

I

.a55!i wo OC .z5zn c ......

N

€01 X S31A30HdWl cOI S3lWOHd WAl ONV 5311HdOYlfl3N '53M30Mn31

. ..

!i

IE I I f

I...... I...... I...... ( ...... b ...... &...... 7 It KI --v) W i I a 0 a I- 3 r' -wz/ 0 /' /

I d N 0 d

sol X S31A30HdlVA1 ONV S3lIHdOYln3N 'S31A30Mfl31 f m

. I

I b

n ...... e.., ksc E? no s2 vt 0

0 0 s: 0 0 N N cOI 513132Vld c 201 X S311HdONlS03 Fig be8 Serial hematocrits for all exposed groups t n 0- x

v) w -J I a 0 CL I- 3 W z

0 0 0 0 0 0 0 0 0 0 -0 0, OD r- lD In s yc) N -

c . 5 -1 -Lr~trochc tlon A study of the nature and extant of the internal radioactive con-

ttirtirratlon in the exposed huuan beings WRS initiated on the 16th * post-drhonation, clth the collection of a-hour urine samples from the Eowelap, Ailhgnae and Bmerican groups. kddltiond lnfonnatioc on the extent and nature of the racEoaeti= contaninatlon was obtained ficm donest5.c anhdls, foodstuf'fs, nater and soil collected on the con- trainate2 atolls and sent to th~U. s. TimaVal P&iolo&cdl Defense i,abor- atary# the ??malILedical Research Institute, the Ikw York Office of

i. Opratiom of the Atonic en erg.^ Comission and the Los Qm~s Scientific Loboratory for gross aetivlty zeasurenenfa and radiochcnical analyaea,

Datz or. soil, water and plants '001~necessazy to determine the feasi- blliiq of utllLz~the foodstuffs and liv- awn of the contenJnntsd atolls. Long term etudies of the domestic eninalc: obtscZned are king conducted at the zpjIPX)L, in order to obtain infomation on the poazlbla ncuts and delayed hazard Pran internal radiation. The main findings of ths internal contanination study in the human be-8 and their ern?iromnt are presented in this report. A detslled report on tbe nature and extent of the internal radiation hazard in

human beings end arcL1~al.8, 88 well 88 the contamination of the ermiFon-

mnt sill be presented M addendm report.

5.2 PhpSlCal lbvlmnwnt Studies A comparhon of the food, rmtsr and soil sample8 from R0ng0~~ Utirf% mc? Roqerik indicated a much higher level of conkmination on Rongelap than on the other islands. The actlvlw appeared to be dls-

tributad in fhe 8- manner on aU the Islands. Iu genera, the cow tamination was associated with very fine particulate matter and ra5 uniformly distributed tlrowghout samples of earth, thatch and grass.

Significant amounts of beta ectivitg (1 )u: per plant) BB well as pu239 (I x 10-4=) were present on the external smfeces plec~c et @ days, but only small emounts of beta and no alpha aotlPify were detscted in the edible partiom. Cwomt tree anp, an inportant 1% in the natioe diet, rms found to haw beta activities of the level of 1 p/liter on Rongebp at two months after detonatlon, Fish collected from the Rongehp lagoon were found to have ve2.r high levels cf

aczivity (OJ to 3 pc pr fish) (LS Ute as EO by8 postdetonatlc:;,

The activity found in soil Tias determined to be associated &Jy ria faUout particles of abc~uf 60 p in diameter. Rongslap water sqles frm. both ciaterns and a we-3 (Figs 5.1 and 5-2) had actie-tiec. of about lpc/lfter at 30 days. Sanples of thatoh roofing exhibited

th@ hZgh@st levels Of f&idty the FhySiCd enoiromot. The presencs of ~88detected on tbatch, grass and on plant food, 5.3 Aninel studies

Tne studies on the Rongelap and Utiril: eninals included measure- ment of in-ttrnel radlooctive coiitmination and radiochemical analpis of excreta and tissues. The acute hematolo~iaaland pathologlcsl effects of the expasure, as well as long term effects on those &&c, are being studied. In edditivn, fertility and hatahability studios

161 as moll 08 radiochemical analysis of eg78 laid by hens fron Rongelay were performed. These studies have provided information on tW extent and nafilre of the internal contamination in the oxposed humm beings. For w-le, radioautographs of animal bones prepared by TJSNWL and Argonne Ilaafional Laboratory (5.1) (Flgs 5.3 and 5.6) indlcate the pattern of skeletal d.tstributlon of flsslon products, particulerly the hlgh concpentrations of rsdioalemsnts in the epiphyseal region of the long bones. FWther, information on these aninals (which receive6 a much higher axternel radiation dose than nas received by the nattve group and over 10 times the faternal deposition) should be of con- siderable prognostic value for the human beingso

5.1, FIw!lm Studies 5&1 mcretion Gross beta activity measurements on the =he samples from Rongelap, Aillngnao and Roneerik indicate signLficant contdnatlon in the majority of samples. The vaxiation in bota activity -retea& hours among 5ndhidMs in any one group Is quite lnrge (Tsble 5.1).

If the meQn values of urine aativity of the adults of the three groups 6 meeke nfter expcsure me compared, It will be seen that tihe bnplq group had the highest activity, 1208 d/m/24 hours. The Aillngnao group had 553 d/n/U, hours and the American group had 309 d/m/24 horns. A group of tbe Japan0se flsbermn exposod to fallout from tis

68138 detonation h& a urhe activity comparable to that of the Roqyiiq adult graup. 162 The man activlty of the individuals under 15 pars of we appears to be considerably hrthan that of the adult group. An excanhation of

the group collections aaalyaed by the various laboratorisa bmlved shone;; fairly consistent levels of activity for the individual from day to day. Tihe variation whlch occma is not considered to be excessively largo far this type of study. The activity as function of time fell off rapidly due to the large component of Ea- - LPand other short raw i60tOpe6, For ccmple the R0ngeI.a~group had a mean activity of 32W d/& hours at 46 deys and ac'tiolty of 339 4d24 hours at 90 days. At six months post expame the Rongalap rrrine was found b contain barely detectable mount of beta activity. The resrrlts of radiochemical studic~ of urine indicab that Sre9, Eaw and the rare earth group qqxrently constitute 77 pr cent of the total betta activity at 46 daysc Sr 89 COIF 140 taibutes 40 per cent of the total beta activity, Ea - 11 pr uent the r- earth roup - 25 per oent (of which 11 per cent 3s Law, 18 equilibrium wlth BaUO at this tins), h2Bwas not found In eignificanC momts in any of the urine sanpleLss P man found. on^ in samples analyzed at early *a inhervals, due to Lts relatively short PlhySiCal half life. 5&2 Eatinate Body Burden For estimating tha human body burden of the various fission products, a &-empirical approaoh, involv5ng extrapolation from anfnel data was used, Two Rongelap pigs were kmed after their amrage 24 how urir.ary excretion of fission products mas determined. All tlseues wore mapped for total beta activity, 88 wall LIB for Sr89, Barn and . the ram earth content (Table 5.2). By applslng the ratio of &%mal body burden/urine excretion activities to the Ron@ap native urb

163 I

s~~les.an&med at about the ~~taeposGdetonatlon time, a total human body burden of 0.33 y, for post sxpasure day 82 was obtaLnedo If this total human body burden is separated into its components using

tho ratio of individual isatop ectivities in the urine or in the total body of the animals at this time, the following values for the Rongelap group, 82 dep pbst-detonatlon were obtained: sr89 - 0.19 PC BaW - 00021 p Rare&arthoroup - Qo030 J= others - 0.09 pc The excretion rate of Sr and BE can be described by a ~er function, + = Alt-n where n is 0.4 and is the activity rwainlng In the body at tim t (w).The exponent waa derived from Cwaa*a (5.2) SrW hrrman inhalation data and It corresponds wry closely to I the exponent found in the human radium data of !Jorris (5.3) and Loonoy (5p4)0 Using thls formulation the individwl skehtal bay burdens

extrapolated back to day one are (is follOnS: Sr89 - 1.6 PC Bauo - 2e7 P239 - negative Based on the SrS9 snslysis, the IMter-Ballou fissgon data (505) and ths retention data of Hemilton (5,6), the follovlag est5maka of skeletal beburden in the Rangelap group on daJr 1 were mads8 a) rare earth group - 1.2 @C b) Illa - 6-4 IIC

164 The integrated dose to iodine isotopes (1132, 24 hours was 180 rep. The Bilfnenea Oelues we= then approxinately onrhalf and the American were one-fourth of these valueso On the basis of a radiochemical analysis on pooled urine samples collected frorm a cross section of the Roagelap and American populations, 16 - 18 &!arch, UsBlsmos reported (5.7) the following estimate of fiesions associated with material inhaled and/or lagestsd by the

Rongelep natiw group; - 5.5 fiSSiOm ! 11” s49 - 1.2 123 fisslom’ Daw- 1.0 1d.3 fissions From these dsta, using certain assumptions os to the uptake and re- tention of these rdioelenents by the bow, the folloning estimate of

body burden at one day vas derivedr

89 w Sr 2.2 Bauo 0.34 0.27 Ru 103 0.013 0.015 CZ45 0.19 0.OL

$318 and short lived 1131 eqiiivnlents 5.1 mc 1.9 E)I)

Pu2” aoI.6 ugm The hitiel body burden of 113’ and short 1h6d iodine isotopes, energetically equivalent to $z is Sol mc. The estbabd total

165 I

Integrated dose to the *aid Prom thc iadine iaotopee assuming a 20 per cent uptake& hours and with corrections for hay of the verg short lived isotopes was calculated to be 150 rep for fhe Rongelep natiws and 50 rep for the Americana. It can be been that with wtdely different approaches to tha estlm.stlon of the body burden, the remilts obtained are wry sinilar with the exception of the Bauo estinate.

An attempt fo detect bone-fixed radioactive emitters by DSCUIS af s~~ltl~film badges taped below the knee over the epiphysis of the

tibia on 40 exposed !Jarshallese, pielded negative results. 5A.3 Internal Rcdioactiw Decontamination Stbylens dianine tetxaeetic acid (EVl!A) has been shown to be tho most effective chemical a@nt to date for moblllaing fission products

from the skeleton and for inareasing tblr excretion rate f5.8, 5*9#

5.lOj. Tfifs chelating agent VI=therefore used in a &econ%tauination tierap at'dnpt on a group of seven Rongelap individuela hcming re- latively large mounts of internally deposited radioelemen*&. Orat administration of calcium EDTA, 1 d25 lbs body might ddly for the days increased the wer-all man activity in the 24 hour urinm of the treated people by a factor of 2.5 times compared with the pre- treatment control axeretion. Since the rate of excretion of activit?. at this tine was about 0.1 per cent/U hours, the obsemd increase in excretion did not significantly alter the total body burden. This study and previous animal wrk qpst that EDTA, perhaps orlminisbrod I.V. and at early intervals, might have been of coneidernbly @eater value In iaCreasing the excretion of Borne of the Internally deposited fission products. 53 piscussion The fallout material probab4 entered the exposed pmple thro~h both the inhalation and ingestion roufes. The sisa of the particle to which the fissian pmducfs were adsorbed, as measured ia Ro-lgelap soil aqles, rauged hdm 60 to 200 p in dlsmeter. This relatively large particle size indicates that the probability of inhalation of

airborne conternination was small, This is based on the obaerrration that in general only particles 0.1 to 3 p in diameter roach the alveoll on inhdlrrtion and that larger particles are filtered out by

the nose and upper reqbatog passage and mallorpea (5.11)- In

addition, the lunge and air BBCS of chickens autopsied in the period. 24 to 100 daps pst detonation shoned low levels of contarninetion, while the GI tract and its contents were relatively active. The he11 leve'rs of activity found in the liver are also compatible with this hypO'&esis indicating ingestion as the route of entry. Autopsy find- ings on five pigs indicate substantially the same results. In general the mean gross beta activities In the urhe of Rongelap and Ailingnae groups -re found to be roughly proporUonn1 to the calculated external dDse end therefore to the concentrations of airborne fission products. Rornwver, a comparison of mean beta activities of the dlllngnae and American groups show the latter to have a somarhst lower amount of internal contarifnation than the farmer though the groups reoeived spproxhately the same cal&ted

167 ' external doae. The duhreacs may .ell llo ip the fact that the Bllingnae people contirmed to eat aontmlnated food and drink aon- Mated wafer up to the time of bPBE11Btion. The daerioan pere~wl. probably westad lees oonfaminated faad. Their mafar was distilled and stored in closed conteiners which precluded the pusslbillQ of rsdloaDtiw contmlnatdon. It la also poesible that indoctrination of the Anerloaa grq as to the Inhalation hmard and perhap theb

more adequate shelter wag responsible for fhe lower mount of internel contanination moeived. Radioana3ysls of urlm ~smplesof the Japrllp. ese fishem, who wre exposed to the asme fallout, indicated that

they had reosived approxiaately the stp~w)amount of faternol contamin- ation aa did the Rongelap adult group. The lower urimr activttfes found in the hlarshallese indivit2uala under l5 years mey Indicate &hat with active bone grmth occlrrring, the InternaJly deposited fleeion

pMdUCt8 ~OXWfirmly fixed and therefom le68 readilg

It does not seem likely that the. children were subjected to any lees internal radiociatiwe oontadnation that nore the sdults. 5.6 Conclus5on

The degree of internal rsdiation Ward was too low to haw OOIP trlbuted significantly to the acute raaiation fWm3rome observed, Efforts to correlate Individual bwburdens with their ollnieal or bematolot?;lceS. findings (platelet and white blood dl1-b) were

an~~~~essful.Due to the al3Uty of the skeletal system to anCBtp trate fission products, aqy injury to the bod$ fKrm these infers

168 emitters mould moat like4 be determined by the ?dation effect on the bona. Ths coaeentraMoa and type of internal redioaetire wp. tdnents, howemr, mlnblae tbe probabiUe of aqp sigaSficant long term effects from the internal radiation. The possibility of aynergistlc eMecta f'rom the wnbined exposure to extarnal and near talemnee doses of internal radiatiori Is also verg slight. The occurrence of such a syeergislp has been demonstrate6 whore anhals were subject& to relat3wly high doses of Internal emitters (2 dgm) in addition to high external dosea. Tbo ody suggestion of swh a conbined effect in this Sl~tlOnQQS from the hematological wspcnse obserwd in these exposed human beings, which did not follow precisely the tims course cherecteriet&gUr seen in lower mmmde eMar short exposure to exbrnal radiafion,

169 L. A. modruff, P. F. Gustatson apa A. M. BNSS, ReTJart on biological epecbna wllecbd on Roagelap Atoll in Umch 1954s WHIIP 731. 5d Cman, F. Po, L. E. Farabee aad R. A. Lave, Health physics and mdlcal aspscta of a etrontiun~inhalation bidsnt, AmLm.J. Roent,, Rad, There & Nut. Ked,, 67: W, 1952. 5.3 Norris, P., T. W. Spchm Po F. Gustafson, Studies on the nehbolian of a radium fn humans, Unpublishedo 5.4 ~oomy,W. B., Late effects (25 - 40 years) of tbe emrly medicd ant? Industrial use of radioactive xnatsrials, Presented ln part at tbs 35th annual masion of frmericau College of Surgeone, Chicago, sllfnois, April 9, 19% 5.5 Runter, R. F. and I?. E. EaU.cuP Simultaneous elom neutron fiedon of atom. I. Indi~id~elend total rates of decay of ttre ffssion products, AprU 1949 - USIRDL-65. 506 Hanilton, J. G., The metabolic properties of the fission products end aetinlde elements, Rev, Ked, Physies 20: 718, 1$48.

5-7 Harriss P. So, Personal aomnunication.

5-8 F-9 H. and J. G. f@l%Ibn, The U68 nf chebting agantS foF aecalerat~excretfon of radiaelsmsnts bEcD.947, 1%l0 503 Cahnp So H., J, K, Gong and !.Iq C. Fiahler, StudLee on EDTA trent~ metit of lti&~& radioactive oontaninatioa, EJucleonics 11: 56, 195% 5.10 GongI J. K., 2. L. t¶lrie and S. A. Coho Studies on the treat= meat of internal radioactive oonteminstiono Effect of aircoaim citrate and EDTA on the dlstxibutdon a& excretion of a mktrne of 170

Table 5.1 GROSS BETA ACTIVITY IN VRDE OF ROPGELgp OROW (Urine oolleafed on 46th post-expo- day arrd paluss corrected for decay bank to colleatlon day)

2 120 ?I2 3 150 4 455 634 5 155 ss4 7 810 1933 23 313 9 355 231 40 223 10 33 260 0 980 549 54 80 u 450 1563 69 285 13 340 1677 422 2a 14 780 2460 Mean 165 18 455 1670 404 22 47 77 30 %o 439 34 750 570 37 480 792 40 550 lis3 46 330 495 49 425 0 52 780 0 55 320 la33 56 700 Z2a 20 57 550 lo95 265 58 24 550 750 2179 26 60 810 650 62 580 35 255 980 1935 63 635 2252 36 150 66 39 280 855 1R5 27 650 48 300 2013 67 450 n 290 3453 72 73 230 3 llo 78 75 %5 52 440 79 76 980 465 2033 - 80 540 1353 82 670 ban 439 758 - ZK2 Meen 581 1203

172 .

Table 5.2

8890 5660 660 u 0.40 0.33 12 5.0 2.4 105 022 0.20 102 0 022 1*1 2.3 0.62 0.50 3.3 0.P 0.42 690- - _L_ - %30 5667 665 13 8.7 1.2 906

I,I.

'I Skeleton (total) 8600 5m 530 Live" 27 0.53 0.20 Colon & Contents 16 5 3.2 L% (Alveo1er) 1.1 0.26 0.23 Stomnch 2.0 0.29 0.13 Intestfne (Smell) 2.6 0.83 0.88 Kidney 3.1 0.19 RWtissues -220 - Total 8870 -534 SSmph~e,24 (5/27) 6.2 4.4 0.10 Urine ssmple, 24,hrs e.1 Average far dep 82 to 88 posbeocpom Averam Per Cent of Individual Radioelenente Sr89 e Skeleton 62 6.8 Totel Body 58 6.5 eine (ahre) 69 7.9 i

I !

,

! .I I Fig. 5.3 Autoradiograph of Rongelap chicken tibia, 16 Xp 21 hr* exposure. Animal saorifiosd 45 d.ys poet emposure (Argonne ?iatiortal Labors-).

176 Fig. 5.4 AuforadiogrCtPh of Rowlap pig tibia, 42 bra. expoeure. Anhal sacrificed 58 days pot &qIOosur0. (WiL).

177 Recommendations 1. It is recammended that establlshment of a medioal tam on a contlnulne basis, prepared to handle emergency sltuatione connects0 with radiation be considered. puelif'5ed personnel shmrld be des5gn- ated by name, afnlmal clinlcal and research procedures aonsldered essential should be established and necessary equipmbnt should be

8 tockpilea, 2. It is recommendea that stqs be taken ta obtain addition12 data in the laboratory In the follawlng oategoriesr n) The bematologlcal response af large animals, Md pn- ferab3y man, arcposed to radiation produeiq the depth-do- curve seen with fallout gmma radiatdon from a plane ileld. Data aeU beyon6 the d 3-d~period, e& preferably for at least a par attSr expomue are necessarye

b) The response of human akin to beta radiation under cos- ditions of dFfferent beta energiee, 8ourcm 85.~88, aad wurce pw mctr1EO.Y