Document 6b6GEkR81KjLddmvjay705jd4

f PROCEDURE OF THE MEDICAL SCHOOL AND THE UNIVERSITY IN THE MATTER OF HUMAN EXPERIMENTATION of lead in the air and repeating the observations throug as may be necessary to obtain a stable curve. (Obviousl somewhat below the slightest concentration that will ind The full protocol of these related experiments extensive for presentation here, it is anticipated that be continued for some additional years. Purpose of Study The primary purpose is to explore and reveal t the metabolism of load in the intact, healthy human orga conditions. The practical objective is to relate the ph lead to conditions of environmental exposure to lead, an the differentiation of safe from dangerous human exposur respect to occupational exposure, and also in relation t ingestion under basic conditions of respiratory exposure The present experiments are intended to provid respect to the concentration of lead in the air which wi population of the urban centers in the United States, in factors contribute to the dispersion of lead compounds i in the eyes of public officials is, of course, the exten compounds discharged from the exhausts of automobiles ma the lead content of the atmosphere of streets, freeways on the somewhat dubious assumption that other sources, c proportions.) K 003236`u response. (Previous experiments have been carried out u more intensive exposure, but always below the threshold the concentrations of lead In the tissues, body fluids, been found in association with the mildest manifestation present experiments do not approach threshold levels,) (b) Despite the lack of hazard, and in order data, the subjects are maintained under the supervision to the best and most exacting medical regimen) of a phys otherwise for the experimental regimen, and has the auth experimental exposure to lead for any medical or hygieni valid. A medical examination is carried out, weekly, an this physician, and certain observations of the laborato some at weekly intervals, for the purpose of a meticulou status of the subjects, as well as for the gathering of Previous Work Done in this Area Two publications (reprints) which are little m methodology and the principal results, are submitted her Method of Procuring Subjects All but two*of the subjects engaged for these more than a score in the past thirty years, have been o as non-academic members of the staff of the Kettering L that are regarded as adequate, reimbursing them complet expense (food, special clothing, and certain medical exp These were members of the research staff during thei Each subject has been selected after exhausti to determine his phyalologioal fitness; each subject ha prophylactic medical and dental care that has been indi during the preliminary period of normal or basic metabo afterward if necessary. Each subject has been interviewed by the prin most thorough and informative maimer, with respect to t experiments, the potential riska involved (on the backg experience of the investigator in industrial practice i one subject in this entire period of time has failed to respect, and, in this one instance, the subject became somewhat exacting regimen after a few months, and wishe some financial advantage was being exploited at this ti not the primary consideration). No written agreement or waiver has ever enter and with all due regard for the provision of a record t and position of the principal investigator and that of facts be questioned and a claim made, it Is our informe on the part of the subject is worth, in law, the paper and also that no document can substitute for or guarant that sees, first, the service to mankind that can be re in addition holds firmly in mind the plain duty not to well-being of the subject in any manner that is known o K* 0012368 of the University ia defined and limited by this arrang however, thut these legalistic considerations do not re the direct professional responsibility of the principal fulfillment of the most exacting ethical requirements f safety and well-being of the subjects. 0012369 O o* V) m CO Ol o o \u Evelyn V. Hess, M.D. Chairman, Faculty Committee on Research University of Cincinnati Cincinnati General Hospital Cincinnati, Ghlo 45229 Dear Doctor Hess: I am entirely willing to provide the information whic I hope, that which is necessary at this time. I wish to make it quite clear that what is under way, "new project," It is rather the continuation of a sy began in 1939, to examine many aspects of the behavio The general plan was interrupted some years ago {abou into the practical significance of lead in the ambien what level of the concentration of finely divided (pa to b at, or near, the maximum concentration which wo by average people in the general population. This interruption has come to an end with the complet (which, we believe, have produced an answer to the qu taking up where we left off at the end of 1958, in th dimensions of the dispersed particles of a specific c Pb2 0 3 , in the respired air, on the rate of accumulati and the rates of increase in the concentration of lea output of lead in the urine. The level of exposure of a female subject is to be ma 0.15 mg. of Pb per cubic meter of air (the actual exp under the experimental conditions to be described, ha until January of 1971 or thereabouts, dependent upon observations). The experiment then is to continue at above >which is well within the limits of complete saf t ime, so long as the conditions of the exposure are l week (actually here 37.5 hours, which regimen corresp industrial exposure, what with changing clothes just bathing and changing clothes afterward) as the latter controlled within limits which are known to be harmle safety). In addition, thiB subject, in accord with o the surveillance of a physician whose sole function i that she is free of any and all illness, including an which might be believed (or imagined by the subject o experimental factors. He can require the discontinua at any time which is advisable, in his Judgment. About two years (perhaps only 18 months) will be requ after which the particle size will be reduced to abou compounds in this regard, but I am unwilling to sub concentration of a chromate or chromite in the resp implication of these compounds (perhaps only one, b to differentiate between the several compounds) in pulmonary malignancies. I should point out to you that, because of the plac the framework of the original project, and because all aspects of this matter,, from the viewpoint of r that any approval from any source was required for formal report of our procedure has been made, there your information. This statement does not mean tha ourselves to be lacking in any way in our willingne the Public Health Service, the University of Cincin representatives of its faculty. We shall comply, f I would hope, however, that this does not mean that continuation (into exposure) of an experiment which May of 1970,, It is worthwhile, I think, to bear in physiological experiments of this type, and the app their performance, were developed by ourselves many were thought of in the Public Health Service or by the specific subject involved in this case, is suc ethically, among our colleagues, in the nature of t defensively, as a matter of opposition to the prese but rather to clarify the issue of professional and the long run, human experimentation, whether for th must be considered by an appropriate authority in t of the vital requirements of the precautions to be that there be adequate knowledge on which to assess experiment to be undertaken. As a senior-member of status), I find it necessary to abide fully by the their due consideration of the issues involved in a * I have given you something of the plans which I communicated to my present associates). It is appa full of years and cannot be expected to direct this to develop,and I believe I have achieved, a degree gram of experimentation, so that it can be expected longer available to look after it. This means, I t phases of the program to be carried out and that th within the Medical Center as to how best to maintai within the faculty with the work program, and also, as to what information should be supplied by the La Medical College. It is not possible to learn many mineral metabolism in man (or for that matter, the than minerals) without investigating the behavior o 001237i the laboratory, if they are to be sufficiently preci can be expected to be engaged in many activities of Some means will have to be developed to spare the pr expenditure of undue effort and time in reporting an institution. It is also necessary, I think, to keep within this institution. Not only will there be wor Health Service has no responsibility, as In the pres no sponsoring role to play. There is no good reason University of Cincinnati, for example, experimental the U.S.A., should require governmental consent to b land should so specify. It is wrong, I believe, to established in that direction. I think, therefore, it would be well if you (and perhaps others) were to of situation and plan to meet them, rather than to f not designed to deal with matters of this type. Yours s RAK:wb Robert Profess Occupat I wanted to talk to you briefly to let you know tha with other people in the Laboratory, which will ext The one is sponsored by Ethyl Corporation, and an a been made, to be drawn on at the end of the year (o we choose, so as to leave no sums due as of Decembe entire $25,000, I am sure, this year, and the work pace in 1970, Dr. Pfitzer is initiating the work, Coroner's cases will be taken for analysis as they stream of samples from other sources. Dr. Stanley It seems likely that the cost can be assessed again of the number of samples which are analysed during with you about the means of accounting for our cost vacation in August and get back to my desk on Augus instance, is available, but is to be paid in on a bi advice and consent. I trust that this will be suff can, of course, discuss it, if you wish, with Dr. F take it up with Dr. Suskind, later, in view of the arrival. Not that I was sidestepping Dr. Foulkes, complicating matters. N13350.02 The other project has to do with the continuation o directing, in which Mr. Cholak, Mr. Schafer, Mr. Pa Dr. Lerner are co-investigators with the technical I have discussed the prospect for the future with t sponsors - Dr. Jerry Cole, of Lead Industries Assoc Corporation, E.I. du Pont de Nemours, and The Assoc The specific part of this project which has been un past eight years, is in effect a side issue of the of the work began in 1939, and was interrupted by t level of lead in the general atmosphere which is co This problem has been explored since 1960, and has very near the solution. It is planned now to return to the point in the ori departed in 1960, and to resume the investigation f annual rate of expenditure of $75,000. I have made the consideration of the group of Sponsors, and thi CO OC anticipation of approval) between now and the end o o I would suppose that the funds from this source hav in advance, but I am not sure that this is the case prepared to request, unless it is fully understood procedure, or unless you wish me to make a differen VU my assumption that you will consult Dr. Suskind on * for doing so. Sincerely CB-/ Robert A. FROM: DATE: SUBJECT: Robert A. Kehoe, M.D February 14, 1968 Investigations Involving Human Subjects In response to your memo of December 21, 1967, the mate the Research Committee of the Medical Faculty, is forw I have not taken the trouble to reproduce the copies of in my files, but have sent the entire sheaf of informa correspondence, in order that your Committee might be f transpired. It may be that you will wish to have certa information in your files. If so, and if you will retu provide what you require. I Include the correspondence the opportunities afforded for misunderstanding which situation. I do not believe, however, that these excha place in your permanent file. You may not agree with that you and the other members of your Committee will n decision on the matter. In any case, I shall do my bes wishes, to the extent, if you choose, and as I suggeste Committee and discussing some aspects of this matter. The issue here, I may say, is not a matter of form or investigators against unethical action, or accusations the genuine protection of human beings against any type whether through Ignorance or intention. Sincer Robert wp N13350.03 0012374 Letter from Dean Grulee, dated April 4, 1966. Dr. Kehoe's reply to Dean Grulee, dated April 6, 1966. Letter from Dean Grulee to Dr. Edward A, Gall, dated A Report to the Clinical Research Committee on the INVES OF LEAD IN THE HUMAN SUBJECT (First Version) Report to the Clinical Research Committee on the INVES OF LEAD IN THE HUMAN SUBJECT (Dated June 7, 1966). Letter to Dean Grulee and the Members of the Research k'K 00.12375 DATE: December 21, 1967 SUBJECT : Investigations Involving Human Su The Committee on Ethics of Human has reviewed the material you sent - &<> mo on The Committee would appreciate having this with a copy of the information including pr to the Faculty Committee on Research as wel to it. To facilitate the review of proje members of the Committee will be assigned t liaison between principal investigators and Dr. Carl Smith will be the representative f Please feel free to talk with him or, if yo any other member of the Committee, about an may have. Thanks very much. SL:rms Sidney L N13350.04 tfF 001237 University o Cincinnati Lear Bud: I do not understand fully just what it is that the Resea from the indications in your letter of April 4th, in rel on, "investigation of the ?v!otabolisis of Lead in the Iumu my best, however, to provide additional information, in fill the hill, icrhaps, I expect the Committee to under more cautious in these matters than most people would be all knowledge ana skill that I may have, in avoiding any It is not easy to say more than just this, in connection s/?yf_ First, with reference to the means by which the subjects that, conuitionuf upon his being found acceptable, physi oy tne| physicians who act for me (or for any other princ be involved later), the subject is offered employment, a his employment are clearly defined in the business offic conditions with respect to potential risk are explained The principal investigator has been responsible for the of salety that are now operative in the best circles of the lean traces, these having boon worked out over the p clinical anu physiological observations of the employees It has been found that no person is poisoned by load unl of Ic-ca which result in a specific degree of elevation o lean or the concentration of lead in his blood. The qua establishing these criteria have been viewed critically are now agreed upon in knowledgeable professional circle they are entirely sound. They are based on the most rig regarding as signs of load intoxication such biochemical with the porphyrin metabolism which cannot be explained say within our own household, that these standards.have Kettering Laboratory, and that they are applied there mo than they are anywhere else.) The experimental program field is explained in detail to the potential subject, a protection of the Laboratory against the slightest dange vulnerable to illness from the'absorption of lead. Inas the investigation of the intake and output of lead day b all times for the principal Investigator and the respons the Clinical division of the Laboratory) to follow the p the rate of absorption and excretion of lead, while he i and laboratory investigation of the hygienic status of t There is no more informative regimen of medical supervis o 1lowc u here. Second, with respect to the toxicity of the lead to whic the dosage from day to day is never in or near the range intoxication may occasionally be expected to occur. Zn as conducted since 1939, have refined and verified the c if they could ever have been (in the earlier periods of e as proceeding into regions of risk, they can no longer b Incidentally, it is not quite true that "no other measure physician," for the purpose of determining the status of in the original memo. Paragraph (b), page 3, points out maintained under the supervision (in a manner comparable exacting medical regimen) of a physician etc. etc." I r the Research Committee may not know just what such a reg of the Clinical Staff of the Kettering Laboratory have s hardly necessary to set down the details of such a regim adequacy, but it lias been done, and the record can bo su Finally, it is recognized that in the carrying out of hu fields, a certain amount of real risk is involved. This in dealing with most siiedica^problems that require elucida however, that in the field of occupational medicine, the have been productive of disease are often carried out by to subject workmen to unknown risks for the sake of the community. It is not necessary, therefore, as a rale, t blindly. One can easily, therefore, take the point of v risk whatever in investigating th#parameters of human p S KAK:wp il