Document r2yd6R5qE4eYEMGrdwLVpE0

October 28, 1962 Br. Richard A. Prindle, Medical Director Deputy Chief, Division of Air Pollution Public Health Service Washington 25, D.C. Dear Doctor Prindle: Please accept my thanks for your letter of October 10th in which you point out the unsatisfactory spots in the subject investigation as reported. I cannot say that 1 am actually "disturbed" by the defects in the investigation or the report, but I agree that some further observations should be made so as to be able to answer any question which exists. Inasmuch as I am able to keep myself informed as to any difficulties that might conceivably arise, I am disposed to postpone the further observations until an appreciably longer experience has been fulfilled. In ray view, certain periodic observations will be required from time to time, and I expect (so long as I am on the job and have any influence) to see that the industry keeps itself informed. I am sending two (2) copies of the final version of the report, with the request that you replace the earlier copies and have them either returned to me or destroyed. The latter is simpler, of course, and I merely wish to get them out of circulation. The final version differs from the earlier copies in that a few sentences have been deleted (as a matter of professional courtesy), a few clarifying additions have been made, and a number of typographical and printinge r r o r s have been corrected. If you wish to have additional copies, just let me know. We had some earlier correspondence about the Harben Lectures, and I am not sure that you have received such copies as might be useful. I shall be pleased to send cloth-bound copies to such persons as you may designate, on the basis of need or special interest. Sincerely yours, Enel: 2 copies of report RAX:ss Robert A. Kehoe, M.D. N9583 DEP ARTM ENT OF H EALTH , EDUCATIO N, AND W ELFARE PUBLIC H EALTH SERVICE WASHINGTON*j, D. C. BU R EA U O F ST A T E SERV ICES Referto I A P :O C O ctob er 10, 1962 D r. Rob ert A. Keh oe Ketterin g LaboratoryCollege of M edicin e - Ed en Aven ue C in cin n ati 19, Ohio D ear Dr. Keh oe: T h an k y ou fo r y o u r l e t t e r o f 18 Se p t e m b e r r e la t iv e t o o u r t e le p h o n e c o n v e r sa t io n of 17 Se p t e m b e r . A s I e x p r e sse d in ou r co n v e r sat io n , I fin d m y se lf con cer n ed w ith th e two item s in the r e p o r t on the in v e st igat io n s of th e u se of tetr am eth y l le ad on th e W est C o ast . T h e se it e m s r e la t e to th e in co m p le t e n e ss of th e c lin ic a l in v e st igat io n s an d to th e ch an ges in th e blood h em oglob in an d ery th r ocy te coun t o b se r v e d on th e su b je c t s. A s you in d icated in you r le t t e r , one can n ot h elp but be d istu r b ed by th is in co m p leten ess an d alth ough it , in it se lf, m ay p rove n oth in g ''p r o " o r "c o n ", it ten d s to le av e one w ith le ss so lid grou n d upon w h ich to stan d . Th e ch an ge in th e ery th r ocy te coun t an d h em oglobin m ay or m ay not be r elated to effects of tetram eth yl lead on the eryth ropoetic sy st e m . H ow ever, in an in v estigation of th is ty p e, it is d e sir ab le to h ave a reason ab le explan ation . In view of th ese p r o b le m s, it w ould ap p ear m o st d e sir ab le fo r fu rth er stu d y to be u n d er tak en a s a con tin u ation of t h is p r o je c t , p e r h ap s w ith K &T0O& N9583.01 2 au gm en tation of both stu dy p r o ce d u r e s an d su b je c t s. I w ould h ope, t h e r e fo r e , th at you r organ ization m igh t con tin ue su ch w ork an d p rovid e the ad dition al in form ation . Again , let m e e x p r e ss m y ap p reciation fo r the opportun ity of review in g th is m at e r ial an d d isc u ssin g it w ith you. Sin cerely y ou rs, R ich ard A. P rin d le, M edical D irector Actin g Ch ief D ivision of A ir P ollu tion 0u0'( Ju6 September 18, 1082 Air Mail Dr. hichard A. Prictdie, Medical Director Deputy Chief, Division of Air Pollution Public Health Service Washington 25, D.C. Dear Doctor Priadle: Following our telephone conversation of September 17th, I came to the conclusion that it would not be inappropriate for me to make a few comments on certain features of the report which I supplied to you ana your colleagues on the investigation of certain aspects of the use- of tetramethylleud on the West Coast. There were two points in this report which could be expected to receive special attention, and it was to these, unerringly, that you directed your remarks to me. I refer ol course, to the omission of the detailed data of the final clinical survey, and to certain hematological findings. i would expect any experienced investigator of population groups to be disappointed and, in some degree, frustrated, as I was, by our failure to complete the work represented in the orderly design of this experimental program. It is a shock to one's logical and even aesthetic sensibilities to encounter such a void, and especially to be a party to it. On the other hand, from either the practical or the strictly factual consideration of the weight of evidence, this is not a serious delect in the investigation in this instance, and for a very excellent reason. It is, in fact, comparatively unimportant that the effects of 'the exposure to, ami the absorption of, lead on the part of these men, were not examined in minute detail, since the incontrovertible evidence is uvailable to demonstrate that they absorbed no loud in the course of 18 months of their employment (or so small an amount, if any, as to be masked completely by some other environmental factor which actually reduced their over-all exposure to, and absorption of, lead.). One can argue in and around thi3 point, and through a variety of strategic questions and answers, but he cannot get away from this com pelling fact. IVhat matter, therefore, that the clinical observations are incomplete? The matter is that neither you nor I, nor any of us, like the appearance of an abandoned scheme of study. It suggests to us things that we do not put into words. However, as a cautious industrial physician, I am constrained to acknowledge, despite ray irritation over this matter, that, aside from the niceties of an experimental program fulfilled to the letter, my medical colleagues in Standard Oil Company of California ~ who aye good responsible internists, but not epidemiological investigators - had fairly good Justification for their conclusion, that the repetition of the detailed examination would be an utter waste of time. N9583.02 Dr. Richard A. Prindle, 2 September 18, 1962 Till3 brings me to consider again the apparent modest increase in the average numbers of erythrocytes and in the concentration of hemoglobin which occurred during the 16 months of these observations, is this related to the absorption of lead? The answer is an unequivocal negative, and this is the point of the issue. Why is it unequivocal? Because of the evidence obtained by the analysis of the blood and urine, it is clear that the negative findings in the blood do not prove that no tetramethyllead was absorbed (they do prove that no significant quantity of inorganic, airborne lead, in excess of that being absorbed prior to the introduction of tetramethyllead into the gasoline, was being absorbed); the negative findings in the urine, however, do prove that no significant quantity of tetramethyllead was being absorbed during the period of the observations. However, there is another factor here to be considered. Even if tetramethyllead had been found, by other means, to have been absorbed, it would not have produced the hematological results observed. It has been established that the absorption of the organolead compounds, tetraethyllead and tetramethyllead, does not exert an erythrogenic function and that it does not alter the metabolism of hemoglobin so far as such effects can be discerned by ordinary clinical observations on the peripheral blood and by analysis of the urine for various prophyrins. Here again, we are disturbed (our statisticians are unhappy) by this unexplained pair of findings, and we speculate on what may lie behind it. This suggests the desirability of further observations, and I shall feel better about the matter m e n such observations have been made and recorded. But without being swayed toward an improper regidity of opinion, I think it unlikely that further observations will explain these related phenomena, unless one makes a sharp issue and a major project out of a further investigation. I am not discrediting, in any manner, the procedures of careful clinical investigation. As you are aware, I am sure, I have long been an exponent of the careful and ever more careful and complete collection of clinical data as the subject matter of the epidemiological work in this field. I cannot ignore the fact, however, that the physiological data in this situation are of much greater significance than are even the most exacting clinical observations. It is because of the sound back ground of information which Implements the interpretation of these data that I have a strong sense of security in the position that I have taken in this matter. Sincerely yours, RAX:ss cc: Dr. W. Clark Cooper Robert A. Kehoe, JI. D.