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Memorandum On th e Development o f th e K e tte r in g L a b o ra to ry o f A pplied P hysiology in the C ollege of M edicine of the U niversity of C incinnati. N ear th e end o f th e sc h o o l y e a r in th e s p r in g o f 192^ P r o f e s s o r M artin H. F is c h e r and A s s is ta n t P r o f e s s o r R o b ert A. Kehoe o f th e P h y sio lo g y D epartm ent o f th e C o lleg e of M edicine o f the U niversity of C incinnati had a co n su ltatio n w ith o f fic ia ls of th e G e n e ra l M otors Chem ical Company o f D ayton, Ohio c o n c e rn in g a ty p e o f p o is o n in g t h a t h ad d ev elo p ed among workmen engaged in th e p re p a ra tio n of a product co n ta in in g te tr a e th y l le a d , a newly discovered and to x ic o lo g ic a lly unexplored a n ti-d e to n a tin g agent fo r use in th e f u e l o f in te r n a l com bustion e n g in e s. I t was ag reed t h a t D r. K ehoe, who had b een s tu d y in g heavy m e ta l p o is o n in g , sh o u ld spend th e summer c a r in g f o r th e s ic lt men^and i n v e s t i g a t i n g th e h y g ie n ic problem in th e p la n t o f th e G eneral M otors Chem ical Company. D uring th a t summer, and throughout th e n ex t academic y e a r, (on a p a rt-tim e b a sis arran g ed w ith th e consent o f th e P ro fe sso r o f Physiology so as not to c o n f lic t w ith r e g u la r te a c h in g d u t i e s ) , Dr. Kehoe worked in a sm all la b o ra to ry of G eneral Motors R esearch C o rp o ratio n , stu d y in g the n atu re of the in to x ic a tio n Induced by te tra e th y l lead and inves N 6512 2- - tig a tin g means fo r th e c o n tro l o f dangers a r is in g in I t s m anufacture and u s e . By th e tim e in fo rm a tio n had been o b ta in e d to make p o s s i b le th e sa fe m anufacture o f th e p ro d u c t, i t became apparent th a t c e r ta in p o te n tia l dangers to th e d is tr ib u to r s and h an d lers of g aso lin e and to th e p u b lic were o f c o n sid e ra b ly more s ig n if ic a n c e / in r e la tio n to the co n tin u e d o p e ra tio n o f th e in d u s tr y , th a n were th e h a z a rd s o f manu f a c tu r e , A ccordingly i t was c o n s id e r ^ i^ ^ ^ e ^ s a r y to b eg in c e r ta in .J A r f r ^ v iA i P W'/<? Z3^._---- ------ i lnW strgatrl^g~lSTlrtrTEe p u b lic h e a x tn l^ p e c ts o f th e m a tter.j' W hile th e s e were g e t t i n g u n d er way, a new a lig n m e n t o f th e i n d u s t r y was accom plished in th a t th e E th y l G aso lin e C o rp o ratio n was o rg an iz ed o u t o f Gen e r a l M otors C hem ical Company th ro u g h a p a r t n e r s h i p a r r a n g e ment betw een G en eral M otors and th e S ta n d a rd O il Company o f New J e r s e y , S h o r tly a f t e r t h i s (May 1925) & s e r i e s o f a c u te and f a t a l p o is o n in gs o c c u rre d in an e x p e rim e n ta l p la n t in which" th e te c h n ic a l s t a f f o f S ta n d a rd O il Company o f New J e r s e y , w orking in d e p e n d e n tly and w ith o u t b e n e fit o f the a v a ila b le in fo rm atio n on th e to x ic ity and p h y sio lo g ic KF 0003184 e f f e c t s o f t e t r a e t h y l l e a d , had d e v e lo p e d a new p ro c e s s f o r i t s m an u factu re. The e f f e c t o f th e se tr a g ic and somewhat lu r i d l y p u b lic is e d ev en ts was to aro u se th e outspoken f e a r s o f a number of - 3the dangers of th e use o f g aso lin e c o n tain in g te tr a e th y l le a d were s im ila r in type and magnitude to those a sso c ia te d w ith th e m anufacture of te tra e th y l lead . In response to these fears a general conference of in te r e s te d p erso n s was c a lle d by th e Surgeon G eneral of th e U nited S ta te s P u b lic ^ e a l t h S e rv ic e on May 20,1925* to c o n s id e r e x p e rim e n ta l i f r e q u ir e d , (See P u b lic H e a lth B u l le t in No,15& ), Af t e r c o n s id e r in g th e a v a ila b le in fo rm a tio n i t was ag reed as b e in g th e sen se o f th e conference th a t the P ublic H ealth Service should undertake an in v estig a tio n of the hazards to the h e a lth of the p u U i^auu. re p o rt w ith recom m endations a t a. l a t e r c o n fe re n c e to b e c a l l e d on completion o f th e work. At th e o r ig in a l co n feren c e th e work o f Dr, Kehoe and h i s a s s o c ia te s , on th e p u b lic h e a lth a s p e c ts o f th e problem were p re s e n te d ' in d e t a i l and one phase;;- o f i t , nam ely, th e c l i n i c a l and la b o ra to ry s tu d i e s on men engaged in th e h a n d lin g and use o f le a d e d g a s o lin e was th e c h ie f c o n tro v e rs ia l p o in t in th e d is c u s s io n . S im ila r s tu d ie s It were u n d ertak en ^ o n a 'l a r g e r sc a le ^ b y th e P u b lic H e a lth S e r v ic e 3981 these stu d ies co n stitu tin g the e s s e n t i a l b a s i s o f t otaJt. f i n a l r e p o r t , (See P u b lic H e a lth B u l le t in N o ,l65) KB 0003185 That the re s u lts and conclusions of the P ublic H ealth Service p r e s e n te d in J a n u a r y o f 1926 w ere in agreem ent w ith th o s e re a c h e d by Dr. Kehoe and h i s a s s o c ia te s i s m entioned h e re only because t h i s com plete agreement dem onstrated the d is in te re s te d ch a ra c te r of the work done by Dr. Kehoeand e s ta b lis h e d a b a s is f o r th e p r o fe s s io n a l r e s p e c t and c o o p e ra tio n betw een him and th e P u b lic Heai t h S e rv ic e w hich now e x i s t s . W hile th e in v e s tig a tio n of th e P u b lic H ealth S e rv ice was in p r o g r e s s , o th e r ex p e rim e n ta l work begun by Dr. Kehoe was con tin u e d in th e b e l ie f th a t th e in v e s tig a tio n would v in d ic a te h is p o s it io n , b ased upon h is work and t h a ^ f th e U.S. Bureau of Mines and a c c e p te d by th e I n d u s tr y , th a t th e re was no evidence p o in tin g to th e e x iste n c e o f danger to th e p u b lic h e a lth from th e use and d i s t r i b u t i o n o f le a d e d g a s o l i n e . I t had now become a p p a re n t t h a t th e work on t h i s problem was o f a p u b lic n a tu re and in th e p u b lic in te re s t^ a n d i t was recommended by Dr. Kehoe, and sa n ctio n e d by the adm lnistrati#i a u th o ritie s of the U niversity of C incinnati, th at i t should be brought under the sponsorship of th e U niversity o f C incinnati A c c o rd in g ly in th e autumn o f 19 26 th e e x p e rim e n ta l work in th e 0003186 - -5 and c e r t a i n Item s o f equipm ent and c e r t a i n o f th e a s s i s t a n t s who bjdbjeS: t >vCv**- -*** ZtBSS&S&Q&BQSBS&fweve t r a n s f e r r e d to th e p h y s io lo g ic a l la b o r a to r ie s in th e C ollege of M edicine of th e U n iv ersity o f C in c in n a ti. There was now a co m p lete p h y s ic a l and a d m in is tr a tiv e s e p a r a tio n of th e te c h n ic a l developm ental work o f the E thyl G asoline C orporation from th e ex p erim en tal work along to x ic o lo g ic and h y g ie n ic l i n e s , sin c e meanwhile th e C orporation had developed ex ten siv e in d u s tr ia l re se a rc h l a b o r a t o r i e s in Y o n k ers, Met Y ork. T h is s e p a r a t i o n , how ever, d id n o t o c c u r a s a m a tte r o f ch a n c e . On th e c o n t r a r y , D r. Kehoe had re je c te d a proposal th a t a la b o ra to ry and experim ental f a c i l i t i e s be p ro v id e d fo r him in co n ju n ctio n w ith th e te c h n ic a l re s e a rc h l a b o r a t o r i e s o f th e . in d u s t r y , and^ t h a t he assume a f u l l - t i m e p o s i t i o n as d ir e c to r of m edical work and to x ico lo g ic- re se a rc h fo r E th y l G asoline C o rp o ra tio n . T his was r e je c te d becau se i t in v o lv e d th e te rm in a tio n of long sta n d in g ^ n iv ersity a sso c ia tio n s and o b lig a tio n s and because m oreover i t would have meant the removal o f th e experim ental-w ork from a medi-cai. c e n te r o f ^ te a c h in g and r e s e a r c h in xirhich alo n e, in Dr. Kehoe*s b e l ie f ,it could be expected to develop along proper channels. Through th e b alan ce o f 1926, and up to 1930* experim ental work on th e g e n e ra l n a tu re of le a d p o iso n in g , and on th e type and sources KE 0003187 6- - o f le a d exposure in th e American community, was c a r r ie d o u t by a sm a ll s t a f f o f w o rk ers u n d e r th e d i r e c t i o n o f Dr. Keh o e , in th e E ichberg L aboratory of Physiology (M artin H .F isch er, P ro fesso r - and Head o f D e p a rtm e n t). By th e end o f 1929 th e work ha&grown in scope and had a ttra c te d su ffic ie n t a tte n tio n th a t o th er in d u strie s ,f / * had h y g ien ic problem s to i t f o r s o lu tio n . I t became ap p aren t t h a t th e tim e had come f o r ex p an si on o f ....th e -w o rk . A c o n fe re n c e betw een Dr. F is c h e r, Dr. Kehoe and th e r e p r e s e n ta tiv e s o f E th y l G asoline C o rp o ratio n , G eneral Motors C o rp o ratio n and E. I . duPont de -c - Nemours and Company r e s u l t e d in a program f o r th e e s ta b lis h m e n t o f a new and a d e q u a te ly eq u ip p ed l a b o r a t o r y . T h is program when M developed brought in to being the K etterin g Laboratory of Applied Physiology. A co n tract between the U n iversity and the donors of th e la b o ra to ry s ta te d th a t th e g i f t o f funds fo r b u ild in g and equip p in g th e la b o ra to ry was w ith o u t c o n d itio n , except th a t th e U n iv e rsity a g ree d to com plete th e b u ild in g w ith in th e funds a l l o t t e d . The U n iv e rs ity fo r i t s p a r t re se rv e d the r ig h t, which had never been q u estio n ed , o f p lanning and conducting th e experim ental work and o f p u b lish in g the r e s u lts through th e custom ary s c ie n tif ic channels fo r the p u b lic good. HE 0003188 - 7- A ll funds fo r th e su p p o rt o f th e ex p erim en tal work w hether p ro v id ed "by th e i n d u s t r i e s i n i t i a l l y r e p r e s e n te d o r by o t h e r s , w ere to be given to th e U niversity and adm inistered by th e U n iv ersity a u th o ritie s in acco rd an ce w ith t h e i r g e n e ra l policies^iwa^ab^A'^'CgacM. to com pensation o f p e r s o n n e l and th e expense o f o p e r a tio n . Any f i n a n c i a l su p p o rt fo r an experim ental program was on a d e f in it e tim e b a s is and in v o lv e d no committments beyond th a t tim e, ~t. I t should be sta te d in the in te ra c t of accuracy th a t a proper form al re la tio n sh ip of ad m in istrativ e o ffic ia ls of the U n iv ersity to the experim ental program financed by E thyl G asoline C o lo ra tio n began w ith the form ulation of th e agreement mentioned above. P r io r to th a t tim e , c e r ta in members o f th e s t a f f w orking in th e E ic h b e rg L a b o ra to ry o f P h y s io lo g y , som^>f whom had been members o f th e group w orking w ith Dr, Kehoe in th e G eneral M otors R esearch la b o ra to ry , had been d ir e c tly compensated by E thyl G asoline C o rp o ratio n , KB 0003189 p a r t l y becau se o f th e f in a n c ia l advantages o f th e arrangem ent to them a n d p a rtly f o r reaso n s of convenience. There was no q u e stio n of p ro fe ssio n a l im propriety, but only of a d m in istra tiv e form, sin ce the in v e s tig a tiv e work was c a r r ie d out and re p o r te d in f u l l accordance - g- a s s o c ia te s w ith the knowledge and consent o f th e P ro fe sso r o f P h y sio lo g y . N e v e rth e le s s when th e f a c t s w ith r e s p e c t to th e f i n a n c i a l arran g em en t came to th e d i r e c t a t t e n t i o n o f th e P r e s id e n t and th e B usiness Manager of th e U n iv e rsity , they req u ired th a t a l l workers in th e la b o ra to ry become r e g u la rly ap p o in ted and com pensated members o f the U n iv ersity s ta f f , and th a t a l l funds be adm inistered wholly by th e B u sin ess Manager o f th e U n iv e rs ity on th e in s t r u c tio n s of i t s B oard o f D i r e c t o r s . T his p o lic y was p u t i n t o e f f e c t in 1930 a t some c o n s id e ra b le f in a n c ia l s a c r i f i c e on th e p a r t o f c e r ta in s t a f f members, b u t w ith complete and a c tu a lly e n th u sia s tic acceptance of i t s ju s tic e and p r o p rie ty . Since th a t tim e a l l funds accep ted from in d u stry in support of experim ental p ro je c ts have been approved by the Board of D ire c to rs a f t e r exam ination o f th e f a c ts and a f t e r agreem ents ex p re ssly p ro te c tin g the rig h ts and re s p o n s ib ilitie s of th e U n iv ersity . Moreover a l l fu rth e r a d d itio n s to the s ta f f of th e Laboratory have been made w ith o u t any concern o r knowledge on th e p a r t o f th e p erso n s involved as to the source of fin a n c ia l support of the Laboratory. A ll th e members of th e s t a f f have sh a re d in th e d isad v an tag es a s s o c ia te d w ith th e g e n e ra lly low s a la r y s c a le and th e somewhat u n c e rta in econbmlc s ta tu s o f the U n iv ersity , and in c e rta in advantages such as p ro fessio n al 618000 3X  - 9- ' -- asso c ia tio n s and reasonable se c u rity in tentfre of occupation th a t a c c ru e to members o f a ^U n iv ersity f a c u l t y , as w e ll as the advantage o f freedom from f e d e r a l income ta x e s as em ployees o f a m u n ic ip a l /U n iv e r s ity . The l a t t e r , o f c o u rs e , wa.s one o f th e f i n a n c i a l inducem ents o f f e r e d to p r o s p e c tiv e members- o f th e t e c h n i c a l s t a f f , I{v ' o f h ig h er i n i t i a l compensation and la rg e r o p p o rtu n itie s fo r f in a n c ia l advancement* I t must a lso be reco g n ized th a t the "reaso n ab le i secu rity " re fe rre d to above somewhat more tenuous in the ce.se of the s ta f f of th is labors.tory by v irtu e of the year to year c h a ra c te r o f i t s fin a n c ia l arrangem ents* A ctu ally th e re somewhat g reater se c u rity than is im plied in th is statem ent since the p r e s t i g e o f th e la b o r a to r y has grown w ith th e y e a rs and oppor t u n i t i e s f o r I t s expansion in bo th scope o f work and in f in a n c ia l su p p o rt have been o f fe re d on a l a r g e r s c a le than i t has seemed vzise to a c c e p t. Thus the laboratory has in te re ste d 0003191 I t s e l f c h ie fly and alm ost ex clu siv ely in fundam ental problems of gen eral m edical and h y g ien ic i n t e r e s t , the in v e s tig a tio n of which - might be expected to extend over co n sid erab le p erio d s o f tim e and to in v o lv e a m a in ta in e d o r p e rh a p s an I n c r e a s in g i n t e r e s t on th e ,) - part of In th is connection i t should be l - 10 - p o in ted out th a t as the c h ie f m edical and hygienic co n su ltan t o f Ethyl G asoline C orporation (in a p riv a te p ro fessio n al capacity) Dr, Kehoe tf&fi in p o s i t i o n to know t h a t th e p u b lic h e a l t h problem involved in the d is trib u tio n and use of gasoline containing te tr a e th y l le a d could be solved^in a f in a l sen se, only through the most in te n siv e and ex ten siv e study of th e general m agnitude and the so u rces o f human le a d a b s o rp tio n , as w e ll as th e p h y s io lo g ic a l mechanisms involved in le ad a b so rp tio n and in the p ro d u ctio n of le a d in to x ic a tio n . This phase of th e work of th e la b o ra to ry t h u s.,\a s s u re d o f f i n a n c i a l s u p p o rt fo # a c o n s id e r a b le p e r io d of tim e; and i t might be assumed, i f the p ro d u c tiv ity and q u a lity of th e experim ental work bore any p ro p er r e la tio n to the im portance and m agnitude o f th e problem , th a t i t would never la ck sp o n so rsh ip from o th e r i n d u s t r i a l o r g a n iz a tio n s . The v a l i d i t y of t h i s assum ption can b e st be dem onstrated by re fe rrin g b r ie f ly to the published work o f th e la b o r a to r y s in c e 1930 , and by c a l l i n g a t t e n t i o n to '. ;/ / w , , ^ a y'1L.. t -O- p ) A *. ``C A U -0-^ J L . -'0 0003192 (t s r^ V ,, :f - j - - ---n u X Zl ,