Document DdXaZzBrnK3R74V10YmKKa43O

IN REPLY REFER TO: H UNIVERSITY OF CALIFORNIA LOS ALAMOS SCIENTIFIC LABORATORY (C o n t r a c t W -7405-e n g -36) P. O. Box 1663 LOS ALAMOS, NEW MEXICO June 29, 1955 Dr- Robert A. Kehoe The Kettering LaboratoryUniversity of Cincinnati Cincinnati 1 9 , Ohio Dear Bob: Thanks for your letter of the 2 kth. Harry Foreman told me only yesterday afternoon that he has nearly completed his final draft of the paper on the renal damage associated with prolonged administration of EDTA and he has agreed to send you a copy of this as soon as it is together in one piece. This will be primarily for your own information but we also hope that you will not hesitate to send back any comments which you may have. It appears to us that the injury to the kidney caused by EDTA is a form of toxicity rather unlike that with which we are usually concerned. Most toxic effects result from an actual chemical re action between the toxin and some tissue component. In this situation, it would appear that the EDTA does not take part in any such chemical reaction but its presence apparently produces a local physical-chemical change producing an actual hydrops in certain cells. As I said, we have now observed this clinically in two human cases and I think that Harry has demonstrated the mechanism quite conclusively in rats. As far as the use of EDTA in lead poisoning is concerned, I have had no first hand experience and have depended on what I have learned from others. We have, however, had some interesting experiences with individuals who have absorbed significant amounts of either plutonium or americium. In these cases, we have known with reasonable accuracy the actual body burden as well as the expected rate of excretion in the absence of therapy. EDTA without any question increases this excretion so markedly that it is possible to eliminate a very significant percentage of this body burden which would not be eliminated otherwise. In these situations, of course, we are dealing with quantities of a microgram or less. We simply don't know how effective treatment would be in the case of a massive, perhaps fatal, overexposure. It is difficult to extrapolate these re sults to the lead problem. I have never yet been able to find out what actual body burden of lead is required to produce symptoms of plumbism. We know some thing about exposure levels and excretion rates but it seems to me that we still know comparatively little about retention. It's a great pity that there is not a suitable radioactive isotope of lead which would permit the study of this problem. Very sincerely yours, cc: M. Bowditch H. Foreman File THOMAS L. SHUMAN, M. D., Health Division Leader .m-: June 24, 1955 hjCt&L @?ti!*s&&4t v- 2&<*~--~ & ***?% * /y tf/fT ifc C t /'*** * **-*-*' $vt V L u S Z ^c^ a.itA-jiufcir ffr 'U r r ^ 'T 1 D r . T h om as L,. Sh ipm an H ealth D ivision r e a d e r L.os A la m o s S c ie n tific la b o r a to r y P . O. B ox 1663 B os A lam os, New M exico D ear Tom: I appreciate your cou rtesy in w riting to m e about the H iker advertisem en t and the is su e s relatin g to it, and 1 am glad to have your e x p r essio n of your attitude on t ie con troversy, if that is the proper nam e for it. in sofar a s I am concerned, it is not s tr ic tly speaking, a co n tro v ersy . I have had occasion to sp eak fo r m y s e lf,, and, in so m e s e n s e , fo r tw o o f th e C ou n cils of the A . M. A . , and having spoken on a m a tter w hich co n cern s m e d eep ly and r e la te s its e lf to th e w ise and eth ical p ra ctice of occupational m ed icin e, I am fin ish ed with it, a t le a s t fo r th e p r e s e n t . Vie a r e lo o k in g into s o m e of the te c h n ic a l poin ts involved in.com e experim ents that m ay or m ay not be productive of real and pertinent inform ation, and from that a sp e ct the m atter is un finish ed , a s it m ay w ell continue to be for a long tim e, but I, lik e y o u rself, refu se to engage p olem ic?, which are both unproductive and unduly w earing. In o r d e r to re m o v e m y se lf from what appeared to be developing into a pitched battle m whrch I n e v e r intended to en gage, I w rote to G eorge M aison (of H iker) w hom I h av e know n fo r so m e tim e , explain ing m y p o sitio n and pointing out to him and his a sso c ia te s the situation into w hich they w ere entering som ew hat n a iv ely . Uuite apart from the questions of u tility and safety in connection with the p ro c e d u re w hich th ey advocate - questions w hich require m ore an sw ers than a r e r.ow a v a ila b le - is the b a s i c p r in c ip le o f u s in g th e r a p y a s a s u b s titu te fo r th e prevention c: the absorpti-m of potentially o r .actually dangerous quanti ties of le a d . T h is, 1 a m s u r e ,from hong and w ide experience in the lead tra d es, is a s tu p id and im m o ra l p r o c e d u r e . Ir. the o c c a s io n a l in sta n c e , under a p p ro p ria te conditions!, u nder th e m anagem ent of a w ise and capable doctor, this can bo done, but as a g e n eral m e a su re of prophylaxis it is brutal opportunism u n w orth y c a d o c cox* o f m e d ic in e o r of a soundly s e n s it iv e o w n e r o r m a n a g e r o f a b u s in e s s . It m a k e s ro e cringe.- in b it t e r n e s s and sh a m e at c u r ig n o r a n c e and w e^bess of p rincip le, that som e of our colleagu es are not only w illing but en th u sia stic oand erers in th is m a tter. . In the m a tter of the e ffe c tiv e n e ss of the p rep aration in the treatm ent of lead p oisoning, the cru cial evid en ce, in m y opinion, w ill com e from the study of the sev ere and often fatal c a se s of lead poisoning among children. We are o o o d G o s N9760.01 D r. Thom as L. Shipm an - (2) - June 24, 1955 in our third sea so n of the u se of the agent in that m an ner, and. I b eliev e that the regim en now in u se w ill an sw er a num ber of the q u estion s at is su e in a fa ir ly c le a r cut m an ner. If th is is an a v erage y e a r , w e sh a ll have som e tw enty-odd c a se s w ithin the next four m onths, of w hich under average conditions six to eight would d ie . Thus one d oes not need to draw con clu sion s fr o m the d e g r e e o i `a b a te m e n t o f d is a g r e e a b le but n o t c r it ic a l m a n ife s ta tio n s of the d ise a se , but can judge the issu e (in tim e, if not at once) on the c riter ia o f (1) su rv iv a l anti (2) se q u e la e . The a rra n g em en t betw een our sta ff and th ose of the C hildren's and the G eneral H ospitals is such that th ese c a se s can be stu d ied f a ir ly w e ll fr o m both c lin ic a l and m e ta b o lic a s p e c t s . :We h a v e d ata on som e twenty c a ses of varying typ es, and th ese data are being assem b led for critica l exam ination. This is a fa irly elaborate task , and none of us who a re involved have the tim e req u ired to do it prom p tly, but w e sh a ll get it togeth er even tu ally. Quite frank ly, I am not too m uch im p ressed by the evidence now availab le in the litera tu re on the treatm ent of lead poisoning, so far as I ha ve had tim e and opportunity to exam ine it. One can be highly en th u siastic about the augm entation and the m anner of the elim in ation of lead from the body. This is im portant, but it is not the im portant point. This can a lso bo done ib iriy w ell by the adm inistration o f UAH. The real question is that of the influence of the agent on the co a rse of the intoxication. W ill it reliev o the illn e s s and w ill it sa v e lif e ? We s e e m to have noire d ifficu lty , ev en am ong su p p osed ly r e a lis tic c lin ic ia n s, in getting down to the b a sic question of the prim ary purpose of therapy. This is strange, e sp ecia lly in view oi the e x p e r ie n c e with b.A.L, w h ic h d o e s n ot in d ic a te th a t th is a g e n t i s b e n e fic ia l. One would think that such exp erien ce would have prom oted a healthy skepticism . ' about the b e n e fits c s o - c a lle d .deleading p er s e . I am m o st in terested in the ren al dam age to w hich you have refer re d , and I sh a ll be co n cern ed to know m o re about th is a s fu rth er in form ation d e v e lo p s. The nature and the m ech an ism of the effect in trigu es m e, and if and when yen le a rn m o re about it,; I'll be glad to h ear fro m you d ir e ctly o r through publi cation oi the r su lte, Sincerely yours, RAK ef C . G. : M r. M anfred Bowditch R o b ert A . K eh o e, 2vl. D . K 0008806