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?’arshclleseet.cO, for testinony to the Joint Co~*ittee on I.totic Energy, the Mtd St~tes, for 3 Jme 195’7at the open hmrtigs on ‘T%e Utwe of Radioactive
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I have been askd to surmarize the early effects of exposure of animals and Vn to exter~l radi~tfon with particular reference to the effects of fallout rndiation on the ?krshallese, the Los Alamos accident and radium. In addition I have been asked to comment on the beta burns in the Marshallese and other examples of beta burns. Since my personal e~erience ig limited to the Marshallese and animal experimentation I shall limit myself to these and supply reference material for the others. It is quite impossible to cover all of this material in a of time so I shall concentrate upon the effects of exposure to on animals afi man with a clinical description of the syndrome ness as a function of dose of radiation and hlghllght the discussion with illutrative material collected in the studyof the Flkrshellese (l). My prepared state~ent.includes numerous references anilfurther material that time will not permit discussion of at length here. Radiation sydromes vary as a function of the type of exp~~e, the dose ad the time after exposure to rad~ation. In general rediation injuries can be divfclti The syn3romes of whole body radiation injury produced bypenetrsting ionizing rad:ation which are dose afi tine deperrlent. Superficial radiation burns protiucd by soft radiations (beta and low Radiation injury produced by the deposition of rziiionuclidesuitkin In the latter case the clinical picture varies uith tbe site and amount Ikh-of the above 1s associatd with an early phase in wkich acute ard SiU~E IWy be observed, and a late phase in kkich chronic changes or
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8 of injuqy and the clinical manifestations are vroportiomte M the dose. This is particularly true of the s~romes of w!~olebody radiation. T%e latter is and I repeat, highly dependent on do~e and time af%er exposure. There Ls no s3mple description. The problem is subtle and complex anilone must always bear dose ad THE SY1J3ROMIlSFTW TOTAL RIDY PEWTRATING RADIATIONS The dose dependent syndromes resulting from total body exposure in the ‘nxcmnalhave ‘oeendescribexlin detail and I shall only smmarize them here. For further details one is referred to the following references ( 1 - 12 ). After large doses (approfinetely 6000 r or nore) the central nenous system syrdrome v;,lchcan be abbreviated CNS is produced. Death may occur under the beam while being irradiat~ or nfter some !:cw-s* *he clinical picture is characterized by h~~erexcitability, disorders of eq~ibriu, Incoordiution, respiratory distress afi intermittent stupor. Convulsions may preceed death. Doses capabl”eof producing this syrdrome are al~ays uniformly fatal. If an occasional anfroal,ard presumably man, survives this C1?S nine days for mammals. he has yet to e~erience the gastrointestinal sydrome (GIS), doses in excess of 1500 r is always fatal within three to Presumatilyman also will respond in a comparable manner as laboratory animals. ‘he GIS is so nsmd because-of the markd nausea, voniting, d%arrhea, arxldenudation of the lining of the .wll bowel. The GIS is a unifcmily ffitalsjdrome in most laboratory animls. If the s?lortduration GIS of a few hours resulting from lcuer doses, does zot produce the tbzee to nine day death, the survivors of this syrxlromehave yet to experience the sequelae of bne marrow depression which has been termd the he.mopoieticsyndrome (IS). The HS is not necessarily fatal. It is the clinical picture that is seen in the lethal range for all namnals and in henopoietic depression - namely.granulocytopenia, depregsed defenses ageinst infee t~on,-thrombopenia, ard an=ia with the pcssible resulting infections,
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t PW3, cd hypcxia due to enemla, eny one of which may be fatal. Mkny detsiled - descriptions of the p9thO&eneSi8 of’these phenomena have been published (1-4,12-16). The above picture of radistion syrclromesis based on aninal expertientation; . however, human experience particularly as obsend at IHroshti~ and Nagasaki and in the l’mrshallesenatives has indicntad that man probably corresponds quite closely to the Ceneral mamnalian response outlined above vith the exception of sone differe~ccs in time cf occurrence. The CKS apparently was not observed by the Japanese at Hiroshima ad Nagesaki. Me uculd not expect it to ksve been observed Since doses to produce this syndrome vere veil vithin the area of almost total deduction. The GIS with deaths in the first week are well documented clinically and patholo~ically as are deaths from the HS. %wever in the case of man, third week) and from hemorrha=ficphenomena in the third to the incidence in the fourth veek). XIIthe Japanese, after the and Kzgasaki, deaths from radiation injuries were occurring as Iete ES the seventk week. This is in contrast to other animals where deaths from the acute pkse ,sretuaco.mnonafter the 30th day. Wedictions of the effects of various doses of gamma radietion are essential to military and civil defense planning. If the absolute sensitivity of man to rediatlon were kmovn, and if it were practical to determine the dose to groups urder catastrophe c~nditions, a realistic Houever, these predictions cannot be nade invclved with estirmtion of’dose receival statistical prognosis could be made. accurately at the present time. Problem by the individual, present real practical difficulties. It is probable that dose estktes will be available from dosimetry devices or-froa dose contour lines ad the position of individuals during e~sure. The difficulties or relying heavily on the dose estiaates for a single individual
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% will not be known precisely. The dosimetry device, records the dose or dose rcte, which ~ not reflect acc~etely, because of shielding and energy depe.tienceof the detice, the deposition of radiant energy at tho site of interest, namely the bone marrow ad the lining of the intestinal tract. ‘Theproblms associated with predicting medical effects from physical esth ation of dose can be further illustrated as follows: it is apparent that dose estirietessvailable will be 8ir doses. The dose received by the air is of academic ~nterest only, since the de~ee of effect in Iiting things is due to the deposition of energy and Its distribution in the cr5tical tissues. Accordingly one must knou the depth doEe pattern or more precisely the pattern of absorlxxldose in sensitive critfcal tissues. This problen has been explored e~erimentally at great length and 3s descrikd in deteil in references (17). More need not be said kere other than the feet ttat the unj.fon field of radiation cov~ng at an individual from all directions fs r:cre effective per r in ~ir than dose of radiation of directional quality. In urban areas there may be shielding from the fallout field by buildings or inhomogeneities in the field due to drift in dry windy areas. With the prompt radtation shielding may be ,+@ficant and the proY3mity of large buildings may siously influence scatter and perturb the uniformity of the radi8tion. Lastly a fallout field my be made unidirectional by keavy shielding from buildinge on one side. Thus estimritesof dose calculat~ from dose rates or derived from an inte- @ating t~e of dosimeter that adds up to the total dose receivcxl,or form position of an individual during exposure, cannot be accepted as the best index of the probable fate of this individual, or as the final guide to treatment. The phYSicim IS interested in the individual from the stand-pointof sorting casualties with some chance of swlval and those for whom nothing CEUI & done, and of’ eq~l ~ortance the troop~onnatier Is interested in the over all prognosis of large grcups of individuals in order to r~akeplans for disposition end replacement. These two diff~e~t desires cannot be completely net by physical estlnates of dose. Howev~, nature }.8sbeen helpful.. The manifestations of r&distion jnjury vary with
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t tl,emc)-mt of radiation reccivd. In other wcrds, the s>nptons of the imlivldual or =QuPs Of ~~i~d~ls becones in a sense a persom itiicator of Onest oun fate? Exrcnc’%r accidente (3$6,9) ari the fallout accident (1,18) to be described later strongly suggest that the best Incex of the seriousness of exposure of the indiv5.dual iE the sy~tom.atology, in addition to the physical est~?ate of dose. Rndiation injury is complex and subtle, and the manifestations of the injury vary considerably. h a ~~rJ~rd ~e~se, individuals exposed in the lethal raage, (kere some, but not all, uill die in the first several weeks following expcwre) prognosis. ‘hue they may be divided into three groups h which sAval 1s, res= pectively, improbable~ possible, and pro’bakle. It will be apparent tlxitthere is no Shg~ line of d~~rcation axong the gro-ups. The distinguishing features are severity ad persistence of vojmithg arxldiarrhea. If Voniting occurs promptly or within a fev :;oursand continues ad is folloved in rapid succession b~ prostration, diarrhea, anorexia end fever the prognosis is .Tave: death w533 elnost Definitely Qccur in I@ of the individuals in 6 ceta.stropheattention should be dwotd princip~lly to others for whom t-here ‘ioaitingnay OCC-U early but will be of relatively ~}-ortduration followed period of well being. In this period of well being r~rkai clanges are ta’king piece in the ktempoietic tissues. Ljmpkoq.%es are profcurxllydepressei within k.oursarkire~airlso for months. ~ie n~u’~opliil count is depressed to low the de~ee and t~%e of maximur depression depending upon the dose. Signs
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ternal evidence of bleeding may occur within two to four veeks. This group represents the lethal dose range in the classical pharmacolobticsense. h thiB gTO~ the symptom free period (the letent period) lasts from one to three weeks with little clinical etidence of’injuries other then slight fatigue. At the tetinat~on of the latent period, the patient zay develop purpura,* epilcttionoral au! cutaneous lesiOnS, infections of wounds or burns,”dinrr!:eaor melena**o me mortality uill be sufficient time is provided for bone narrov regeneration the survival rate will be In group 1 (Suwival impossible) and grcup 2 (Sti.val possible) the blood picture is not as well documented as in group 3 (Survival probable). 7%ere are good clinical reasons to believe that in the lethal range the granulocyte depressions 3 during the second week. Cbservat”ons madewill be rmrked ard below 1,000 per mm in JePan confti this contention. However in the sublethal range it takes much longer for the granulocyte and platelet count of man to reach ninimal values, as the data of other mm-mals. Despite the chaotic conditions that etisted in Hiroshima KUcuchi ad hkkisak.a(11) shovs that there was a Gore rapid arxlr-arked groups 1 (Survival improbable) and group 2 (Sunival possible) than in ~oup 3 (Survival probable). Before going on to group 3 survival ~robable, I cannot ref~oin from a cosnnenton therapy. l+~chhas been learned from the experbental tkerapy of radiation injury in ellhlals. It has been conclusively s;.ovnthet protection can be aff6rde3 by the transplantation of bane marrov from one strain of arhal to another. The protection afforded by transplantation of genetically specific mterial, that is from one nember of the same strain to an irradiated member of the same strain, is very good and long lasting. If the material for transplantation hes its-source In acother strain of mouse, the protection “isless marked and not “aslong lasting. If the ‘= Black stools from digested blood
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4 If tk,eprotective r~terial comes from another species of animal the protection is very short lived and not nearly as effective. In principal the transplantation of bone marrow would significantly increase the survival rate of exposed human be!ngs in the group 2 (survival possible) and possiblyto a lesser extent in the group 1 (Survival improbable) casualties. The amounts of bone marrou needed are large and the mongrel nature of man takes it unlikely that very much could be e~ected in tk.eway of long term protective effect. In my opinion it would be the worst type of wishful thinking to expect that one could !ave an effective kone narrow bank in the cGse of an ato,iriiccatastrophe. Mud.vork is yet to be done under carefully controlled clinical conditions before one could be optimistic about the use of this procedure in man under highly controlld conditions, for an individual patient let alone under conditions of a nuclear catastrophe. However, the trea.tientof group 2 casualties is not at all ?:opeless There is ample clinical experience in conditions where the bone mm=row Is swerely depressed and in which there are inadequate numbers of circulating cells. In these relatively conmmn clinlcal conditions producd by sensitivity to drugs, or occurring naturally as disease processes, the combined use of the wide spectrum antibiotics that are now available, and the judicious use of blood transfusions significantly increases the survival the of the Individuals, thus giting nature a longer period of the to repair spontaneously the damages that has been suffered. Accordingly one could feel optimistic in respect to Increasfig significantly the survival rate of the group 2 (survival possible) casualties by vicie b~otics.* Preparation and stockpiling for such an This group co~sists of individuals of availability of enough blood for spread controlled use of antiemergency is obviously required. cay not l,avehad fleeting nausea to a linitd extent for anenfa. The probability burns and other injuries is Iov. Zence uhen blood may be needcxlfor–radiation injury supply my be-‘exbusted.
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‘% and ~omiting on the day of exposure. In this group there is no further evidence tected by serial sttiies of the blood with particular reference to lymphocytes and plctelets. The lymphocytes reach low levels early, within @ hours, and may S!.OWlittle evidence of recove~ for many months after exposure. The granulocytes may show some depression during the second and third week. However, considerable variation iq encountered. The late fall in the grarnilocytes,during the 6tb or ‘Rh week, may occur and should be watched for. Platelet counts reach lowest levels on approximately the 30th day at the ttie when ~axff.umbleeding was observed in Japanese vho were exposed at Hiroshba arrlNagasaki. ‘his the trend in the platel@t count ard the development of h&7Lorrh@? is in rnerkedcontrast to that seen in lahratory animals where platelets reach their lowest levels between the 10th ard In this group inidviduals with neutrophll counts below 1000 per cubic mm. nay be complete by asymptomatic. L~kewise, patients with platelet counts of 75,000 per cubic mm. or less may show It is veil known that all lethal doses of radiation, ad no external signs of bleding. defenses against infection are Iowerd, even by sub- ~hus, patients with severe hamatologic depresefon should be kept under close observat~on and administered appropriate therapy as ~ C?icated. There is reasormbly good animal experbentation to indicate tl,atsublethdly e~osezl colonies of animals are :~:oresusceptible to endtic and epidemic infection. me numbers of individuals in grcup 3 (Stival probable) will be greater than in group 2 (Survival Possible) and the rnmber in group 2 will be ~eater than in ~noup 1 (Survival inprobsble). Group 1 casualties will be Helplessly injural.. Group 2 casualties will be able to help in their own cere to a limited e~.ent. Group 3 ca-sualtieswill be useful and a r.oderatemount of work will riotbe kanxful. No therap:?other than observation is neded for this ~ou.p. The rest-of my co.ments will be focused on the fallout
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i on Wwch 1, 195L. Followinc detonation, une~ected changes in the wind structure deposited radioactive naterfals on inhabited …
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