Document 06E4RzZnr44x0XJNw2Z2g9Ged

ANDREW F L E T C H E R , PRESIDENT K. C . BROWNE LL. VICE PRESIDENT J . A . M A R T I N O . V I C I PRESIDENT M.M. ZO L L R. V I Ct PRSIDENT ROBE RT Ll NDLEy Z I EOF C L D, SECRETARY-TREASUBCR liliiiltiMiwmmmAmmmmmM&m 4 2 0 LEXINGTON AVENUE NEWYORK17,Sr.Y. MANF R E D BOWDI TCH DIRECTOR OF HEALTH AND SAFETY August 3, 1956 Robert A. Kehoe, M. D* Director, Kettering Laboratory University of Cincinnati Eden Avenue Cincinnati 19, Ohio Dear Bob: , I greatly appreciate your sending me a copy of your letter to Dr* George* It strikes me as so admirable and so important that I have sent a copy to Drew Fletcher, both for his own interest and with the thought that he will probably forward it to Mr. L. B. Robinson, Vice-Chairman of the Zinc Corporation in London, the case about which Dr* George wrote you having been an employee of theirs in Australia. Drew and Robinson have been in correspon dence about this matter; as you may or may not know, Drew*s daughter Ann is married to Robinson Junior, I regret to say that, in a letter which George wrote me in June, after his return, he indicated that the Zinc Corporation would probably set tle the case, "rather than draw attention to the new problem* by contesting it, and this is confirmed in a letter which came from him only today* He feels sure, however, that something will ultimately be done about it, and promises to keep me informed. I shall respond to your no less excellent Giesselian communication by separate letter. And the same with regard to your acknowledgment of my "left-handed re marks" anent the case of "Arsenic and Old Luce," as some wit has labeled it, which I am glad to know disturbed you no more than I thought it would. AIR MAIL July 30, 1956 Dr. W. E, George M.Z.L. Building 1:2 Bridge Street Sydney, Bov; South Wales Australia ; Dear Doctor George: ^ At the time I received your letter and also since, I have been pressed for time to such an extent that everything that could he allowed to wait has done so, my correspondence being mainly in that category* I trust that my failure to reply promptly to your letter has not inconvenienced you or led you to think me indifferent or somewhat less than courteous* The problem which y o u present is one that was b o u n d to develop out of the misunderstandings that exist in the minds of many laymen and even among physicians, concerning certain aspects of the behavior of lead. Since the last word on the latter is not in, w ith particular regard to the precise mechanism or mechanisms of the intra- or inter-cellular effects exerted by lead, it is difficult to deal with the p roblem without appearing to bo opinionated beyond the evidence# ^Even so, I cannot feel that we should accept opinions based upon naivete, in preference to those that have developed out of experience and a critical examination of available facts* Therefore, I express my own opinions freely. The evidence, as I see it, indicates clearly that the absorption of lead, within the limits of a certain-range, is entirely without threat of harm to m a n and living things generally, so f a r as we k now the facts in their broad application. This follows from the fact that lead is in the food which springs from the soil of this earth, being, and apparently having always been, in everything that we eat and drink and in the air we breathe. This range is somewhat variable f r o m individual to individual, and from area to area, dependent upon a multitude of natural and artificial environmental factors, but so far as observations have gone - and they have been oxtended far in the last quarter of a century - the entire situation can be expressed in the physiological terms of the ranges of load con centration in the tissues of the bodies, the body fluids and the excreta, of essentially normal persons - i*e*, those not suffering from the more or less obvious diseases that impair, significantly, health and the capacity for the performance of the ordinary tasks and duties of life. These ranges have been described in the literature and nee d not he detailed here. It has also been shown, in m y opinion beyond any reasonable doubt, that S. George - (2) - July 30, 19.96 considerably more than the "normal" range of lead concentration in the body induces h o har m in any anatomical or functional tray that v;e can now detect* At certain critical levels of concentration, as measured directly or indirectly - by the analysis of the tissues directly, or b y reasonable extrapolations based on analysis of body fluids and excretions - the like lihood of harja is demonstrated b y an increasing incidence and severity of s:nnptoms and signs of illness, . *i' ' On this background, which has been portrayed elaborately by intensive and extensive! clinical and physiological investigations, we now turn to the effects off certain agents, of w h i c h only S A L and EDTA, so far as we n ow 'm o w , are of any real significance. Those, w h e n administered in appropriate amounts, change markedly the pattern of lead distribution in the body by inducing a rabid loss of lead from the soft tissues. After this has occurred, tbej normal bodily m e t a bolism gradually restores the equilibrium throughout the body between the skeleton and the soft tissues* Tho total effect, speaking in metabolic terms, is that some load, in excess of that which would pave been lost by normal means, has been eliminated from the body. It is evident that tho administration of either B A L or EDTA to any individual from tho lowest normal to the highest abnormal (in terms of ^ load concentration in tho tissues, fluids and excreta) can be expected to increase the elimination of lead f rom the soft tissues of the body (BAL gives this response more quickly, but less consistently, from the quantitative aspect, than, does EDTA), There ar^e a numb e r of factors, only a few of which are known in any definitive manner, that influence the degree of response to these agents. Certainly the quantity of lead avail able in the soft tissues is one of these factors, out it is not possible, at present, to gauge, with any real precision, the amount of lead avail able in the x,issues, by the quantitative degree of the response to the administration of a certain dose of EDTA over a certain period of time and in a particular manner* All we can do is to generalise by.saying that if the response is great, the quantities of l ead must be considerable. Detailed metabolic investigations, w h i c h have not bee n carried out (we carried out several, brief experiments with B A L and one w i t h EDTA, but I know of no others that have followed the total intake and output of lead by men), would be required to establish the relationships on any sound physiological or even statistical basis, V q have] learned from one series of observations on a single laboratory subject with a fairly well defined and essentially normal body burden (total content of body) of lead, that the response to the administration of EDTA b y m o u t h can give rise to a prompt and appreciable loss of lead from the oody (increase in urinary load output without any demonstrable decrease in tho lead output in the feces). When the opportunity presents itsexf in a professional situation that will justify such experiments, we hope to investigate a series of individuals with considerably elevated and k n o w n ,-- that is approximately known -- b o d y burdens of 'lead, so as to establish standard conditions and valid criteria for the interorotation orge - (3) - July 30, 1956 of the significance of he response to EDTA. This w o u l d be the only m a n s I can think of whereby your problem will be answered satisfactorily, heanwui o. I am convinced, despite all of the difficulties of the situation, ounded on the serious and common bias associated 'with the age- old olicf in the horrible and irreversible effects of lead oo is on ins:i that to typo of reasoning or lack of reasoning that has given I . S < to your problem ough to be combatted vigorously in medico-legal circles, t o "the end' t''hat' Its proponents m a y be compelled to adduce some va l id ev dance in support of their views or else be made to appear ridiculous. I know what you are up against in your part of the world in dissociating the degenerative diseases, particularly the renal-vascular group, from load as a causative factor. The same p r o b l e m exists, in lesser degree and in certain more or less .iraited areas, in this country. 'be work and 'writings of men like 2Tye have convinced a ver y large p ro )ortiozi of your physicians of the reasonableness - nay the certainty - of this relationship. It was virtually a classical doctrine in clinical medicine long before Eye I am quite convinced, from the epidemiological, physiological and clinical work w h i c h T- an(j rny associates have done within ce 'tain yroues over a oeriod of thirty years, that the Idea was wrong In itfcs ince_ption and that it is a magnificent example of post hog medical reasoning, I am also reasonably certain that the Idea can be shown to bo false, when the evidence of Industry can be assembled on a sufficiently wide base, Even after that, however, a long time will lapse before the non-industrial clinicians' w i l -1 absorb the facts and accept them, iOW long, Oh Lord, how long, does a deeply rooted idea persist! 'ear that what I 1 aid w ill not be of m u c h help' to you, but suen as It is I offer It to you A3 ;o ;ne oninlon or n'NV~.g oxee rts" in Ls country on the relationship of lead to the degenerative senses, he best I can do is send you, under separate cover, a document of le position, In the form of' a report, of the A m e rican Public Health Association, This is as nearly "official" as the situation can be made in rue u;,3o,Aa, Ir refer y o u specificalyl,yT to0 ppaaggee 56 0off tthhiiss RReeppoorrtt,, In which this p r o b l e m is discussed. This i`s t'h*e consi.d.e..r.e.d..o.p..i.n.ion of~ the group of experienced observers of this p r o b l e m in this country. It proves no pn m g , jut for the purposes of court action, It digs the ground out from under those who consider that the matter has been decided in general medical opinion. This fact is, on the contrary, that this whole concept has boon handed down from textbook and medical article to textbook and medical article, over such a length of years that almost no one in modern times has bothered to look at the original source of the opinion. It has become an "article of faith," as a revelation from the ancestors of the modern breed of physicians. If there is some real assistance -which I can offer you, please <jo not hesitate to let me know. Sincerely yours, RAK:vr cc - Dr, Manfred Bowdltch Robert A. Keiioe, ii.D,