Document e5QryZ3KyxqZ8eQaGjEdQxD0G

CONFIDENTIAL Au gu s t 2 5 , 19i+8 Bo b , I am g r a t e fu l f o r yo u r f a i r and c a r e fu l fo r m u la t i o n o f th e pu rp o sje s o f th e La b o ra to ry * I t shows me simong o th e r thin gs th at I have been rem iss in not keeping you b e tte r in fo rm e d o f my a c t i v i t i e s h e r e . I am l o o k i n g fo rw a rd to the p r iv ile g e o f ta lk in g the se m atte rs over w ith you as you s u g g e s t e d , ij am t a k i n g the l i b e r t y o f o u t l i n i n g b r i e f l y ray i n t e r p r e t a t i o n o f my b e h a v io r and m o t i v a t i o n , w ith o u t w aitin g fo r the time o f the d is c u s s io n , fo r the problem i s so com ple x t h a t II fe a r I m igh t m is s s o m e th in g I f I t r i e d to p re s e n t a l l th e a s p e c t s o f th e s i t u a t i o n v e r b a l l y , and I am a n xio u s t h a t we u n d e rs ta n d e a ch o th e r b e fo r e we d i s c u s s the d e t a i l e d p la n s fo r the f u t u r e . Fo r i t se e ms t o me t h a t I can be o f g re a t valu e to you and to i n d u s t r i a l h e a lt h , and th a t I would fi n d Ithe r e s p o n s i b i l i t i e s a c c r u i n g fro m s u ch a p o s itio n most s a tis fy in g . ' In t h e co m ple x f i e l d o f In d u s t r i a l h e a l t h my p r i n c i p a l In t;e r e s t s and t r a i n i n g have d e v e lo p e d i n th e b ro a d a s p e c t s o f re s p ir a to ry p h y s i o lo g y and e x p e rim e n ta l m e th o d o lo gy , I include in re spirato ry physiology not only dise ase s o f the lun gs and c irc u la to ry syste m , b u t such co n d itio n s as hemoglobin In a c tiv a tio n , tis s u e u t i li z a t i o n o f^o xyge n , and enzyme i n h i b i t i o n , so the p e r t in e n t c o n d itio n s e xte n d from s i l i c o s i s to l e a d p o i s o n i n g . Unde r m e th o d o lo gy 1 i n c l u d e the d e s ign and e v a lu a tio n o f e xp e rim e n ts , and t h is e xte n d s from e s t im a t in g the param e te rs o f the d o s a g e -m o r t a li t y cu rve fo r animals to the c li n i c a l e valu atio n o f the the rapy o f le a d p o is p n in g i n man. I r e c o g n iz e t h a t I am t r a i n e d as a c l i n i c i a n and c l i n i c a l i n v e s t i g a t o r , and do n o t po s e as a p h y s io lo g is t, a b io m e tricia n , an In d u s tria l p h y s icia n or a co n s u lta n t i n t e r n i s t , n o t because such a c t i v i t i e s would no t be ad m irab le , but be cause I can 't be e xp e rt in a l l f i e l d s . I f r e e l y ackn o w le dge my d e b t t o th e s e d i s c i p l i n e s , and e ve n fe e l th a t I can co n trib u te to the advancement o f knowledge in these fie ld s . To a v o id l o s s b y to o wide d i f f u s i o n o f s u ch tim e and a b i l i t i e s th a t are a v a ila b le to me, I have s tu d ie d in te n s iv e ly in the ye ars I have been he re ce rta in s p e c ific pro ble m s w it h w h ich I have come i n c o n t a c t . What I want t o do now i s to In c r e a s e my e ffe c t i v e n e s s by g u i d i n g th e e f f o r t s o f o t h e r s i n th e s e same f i e l d s , fo r t h e r e i s to o much fo r me to do a l o n e . I Would l i k e t o o u t l i n e b r i e f l y th re e e xam ple s o f th e s e e f f o r t s to d a t e . The f i r s t , and w hat se e ms to me o f the most immediate im portance (altho ugh the le a s t f r u i t f u l as y e t) has been a s tu d y o f the d a ta o b ta in e d fro m N24703 -2- men e xpo s e d to l e a d , o ve r th e l a s t f i v e y e a r s . I t soon ap pe are d to me t h a t i f I was to make any c o n t r i b u t i o n to yo ur work i n t h i s f i e l d t h a t I ne e de d to know more than I d id a t t h a t tim e about the measurement o f v a r ia tio n and co nco m itant v a r i a t i o n . 1 s u b s e q u e n t ly fo u n d , and my e x p e rie n c e w ith de com pre ssion s ick n e s s co nfirm e d t h is o b s e rv a tio n , th a t w hile my own kno w le dge was l i m i t e d , o th e rs to o had n o t known enough to co m p le te ly re s o lv e t h is problem o f the measurement o f v a r i a t i o n .! I f e e l now t h a t I do know e no ugh t o f i n i s h the work I have be e n t r y i n g to do fo r fi v e y e a r s , and agre e d to fin is h th is ye ar: p re s e n t, w ith your h e lp , the e ffi c i e n t ly an alyze d and c o rre la te d d a ta w ith a d is c u s s io n o f th e in fe r e n c e s t h a t may be draw n s a fe l y t h e r e fr o m . My ap p a re n t w ith d ra w a l in to an iv o r y tow e r has n o t bee n fro m ig n o r in g the proble m b u t fro m a t t e m p t in g t o m a s te r i t . I t has re q u ir e d me to c r i t i c i z e J. C . I . m an u s crip ts and s uch work as Mirs k y ts and Bro h -Ka h n ' s , b u t t h i s h as be e n a s p e c i f i c c r i t i c i s m a lo n g the se very lin e s . In cid e n ta lly , the le tte r s * paper pre se nts some o f th e me thod o f a n a l y s i s in a q u i t e s i m i l a r fa s h i o n to th e way i t m ight be a p p li e d i n the s tu d y o f le a d p o i s o n i n g . The s e co nd e xam ple i s th e s tu d y o f e t h y l v a n i l l a t e and e t h y l fl u o r o a c e t a t e . He re I fo u n d my p r i n c i p a l l i m i t a t i o n i n t h i s typ e o f r e s e a r c h was a g a in my l i m i t e d kno lw e dge o f b i o l o g i c a l v a r i a t i o n . I soon fo un d t h a t o th e rs to o were in v e s tiga tin g in th is fie ld w ithout a true understanding o f e ffi c i e n t methods o f re s e a rch . Ea rly I atte m pte d to fo rm u late a do s age s ch e d u le b as e d on th e known b e h a v io r o f a n i m a ls , a lo n g the ^saine l i n e s ta k e n b y De ichm ann and Le B la n c . A f t e r my d i s c u s s i o n s w ith De ichm ann he g e n e r o u s ly o ffe r e d t o in c lu d e me ajs a c o -a u t h o r o f h i s p a p e r. With a l l due r e s p e c t t o b o th o f th e a u th o rs and ackn o w le d ge m e n t o f my de bt to the m , I f e l t t h e i r pape r was lim ite d fi r s t " by th e dosage s ch e d u le the y u s e d , and se cond by the fa i l u r e to p re s e n t a wajy o f e s t i m a t i n g th e e r r o r s o f th e e s t i m a t e s . It has been th is study which le d m ainly to the de lay in the fin is h in g o f the e thyl v a n illa te paper, fo r that paper depended upon th a t ve ry method o f v e r t i c a l dose s t r a t i fi c a t i o n fo r It s v a l i d i t y . F i n a l l y we had to f i n i s h th e p ap e r an yw ay. At th e moment I am s t i l l e n gage d In t r y i n g to e s t i m a t e t h e s e e r r o r s , fo r I am n o t s a t i s f i e d w it h t h a t s t u d y In i t s p r e s e n t s t a t e . I t h i n k t h a t i f I am s u c c e s s fu l t h a t t h i s w i l l be an im po rtant c o n trib u tio n to pharm acology and to the s p e c ific methodology o f th is lab o rato ry. The t h i r d e xam ple i s my p r i v a t e p r a c t i c e . You a re w e ll aware t h a t I p e r s i s t e d in my e f f o r t s to p r a c t i c e c l i n i c a l m e d ic in e , e ye n th o u gh i t c o s t me and my fa m i l y ( and s t i l l do e s), a conside rable fin a n cia l s a c r ific e , la rge ly because I f e l t the s tu d y o f p a t i e n t s was an a b s o lu te e s s e n t i a l to my r e t a i n i n g and e n h a n cin g my c l i n i c a l s k i l l , and b e ca u s e I was un able to p r a c t i c e h e re o r a t the Ho lm e s , ^he re w e re o th e r re as o n s fo r p r a c t i c i n g , o f c o u rs e ; one o f them was the u n ce rta in ty th a t I would be s u c c e s s fu l as a c l i n i c a l i n v e s t i g a t o r . I am s t i l l co n v in ce d t h a t p r a c t i c e i s e s s e n t i a l te I 00026 3- - fo r my typ e o f r e s e a r c h . Of c o u r s e , I w ould l i k e to p i c k and ch o o s e my c a s e s , b u t t h a t tim e has n o t y e t come; so i n o rde r to g e t e s ta b lis h e d I have had to se e p a tie n ts s u ffe r in g from n o n -c a r i a c and n o n -r e s p i r a t o r y c o n d i t i o n s , Ho w e ve r, a p a r t o f my work c o n s i s t s o f t h e s u rv e y o f s e v e r a l gro u p s o f e x e c u tiv e s , and I b e lie v e th a t the s e s tu d ie s in t h e i r scope and o b je c t i v i t y compare fa v o r a b ly w ith th o s e th a t anyone e ls e has done o r w i l l be a b le to d o . A gre a t d e a l o f the tim e 1 spe nd i n my o f f i c e i s p u r e ly i n o rd e r to be a v a i l a b l e t o p a t i e n t s , and I do much o f my r e s e a r c h t h e r e . P o s s i b l y fo r th e s ake o f my fa m i ly I h ave be e n unw is e i n n o t t r y i n g h a rd e r to g e t known; I have p r e fe r r e d to us e my fre e time w orking n ig h ts and e a r ly in the morning h e re , s tu d y in g lu n g gas e xchange and the methods o f measurement o f lu n g d i s e s e . I h ave u s e d my p r i v a t e p a t i e n t s to t h i s e n d , A s u p e r i o r method o f d o in g BMH' s , and a s tu d y o f th e r e l a t i v e im p o rtan ce o f p CO*, pO* and lu n g volum e on the s tim u lu s to bre ath e , are the most im portant immediate problems th at are near s o lu tio n . I have a burn in g d e s ire to m aste r th e s e fi e l d s and c o n t r i b u t e tb th e advance m e nt o f s c i e n c e . As I s e e i t , I am l i m i t e d now l e s s b y l a c k o f kno w le dge th an h e lp and s u p p o r t . I t se ems e s s e n t i a l t h a t I d e l i m i t the f i e l d o f my i n t e r e s t s so as n o t to| d i s s i p a t e my e n e r g i e s , fo r th e pro ble m s I w o uld l i k e to s t u d y a re s o v a s t a s to be In s o l u b l e b y my p a r t i a l and u n a s s is te d e ffo r t s . I have s u gge s te d a se parate la b o r a t o r y n o t to d is e n g a g e m y s e lf from o th e rs h e r e , but to a llo w o f the fo rm al re c o g n itio n th a t t h i s i s a fi e l d w hich i s b e in g s t u d ie d p r o d u c t iv e ly and a u t h o r i t a t i v e l y by e x p e r t s . Of c o u r s e , lit n e e ds th e a c t i v e s u p p o rt and In t e r e s t o f th e o th e r members o f th e l a b o r a t o r y ; t h e i r kno w le dge and s k i l l i s in v a lu a b le . I would want to be re s p o n s ib le fo r the te a ch in g o f the Fe llo w s in the fi e l d s o f r e s p ir a to r y p h y s io lo g y and c l i n i c a l m e tho do lo gy; i f th e y wanted to h e lp In our r e s e a r c h I w ould be more th an p le a s e d , ^ t ju s t as Ch o la k i s r e s p o n s i b l e f o r h i s men and h i s e q u ip m e n t, s o I w ould e xp e ct to be o f m ine . It| Is n o t to my i n t e r e s t to h ave th e s e pro ble m s In d e p e n d e n t | o f yo u r re v ie w - the pro gram In c lu d e s fo rm a l ap pro val and I should hope fo r your a c tiv e in t e r e s t . I need i n a d d i t i o n ra n k s u ch t h a t I am r e c o g n iz e d a s a r e s p o n s i b l e in v e s t ig a t o r In o rde r to have the r e s p e c t , a u th o r ity and p r e s t i g e to c a r ry o u t t h i s work w ith f a c i l i t y and h e lp my a s s o c i a t e s i n t h e i r s u b s e q u e n t c a r e e r s . I have o b s e rv e d t h a t an i n v e s t i g a t o r works b e s t when the men unde r him a r e r e s p o n s i b le s o l e l y t o h im , and i f th o s e to whom he i s r e s p o n s i b l e t r u s t in laifge de gre e in h i s wisdom in h e e d in g the a d v i c e , d e s ire s and ic r it ic is m o f o th e rs in h is ch o ice o f the proble m s to be s t u d i e d In the f i e l d i n w hich he i s e x p e r t . I w ould e xp e ct to have re fe rre d a l l problems In th e s e fi e l d s th a t come t o th e a t t e n t i o n o f th e la b o r a t o r y and to be g i v e n f a c i l i t i e s to ad e q u ate ly study them. I fe e l th a t a s tudy o f s u ch p a t i e n t s would be e s s e n t i a l to ke e p me and my te 00Q27 -4- fe llo w s o rie n te d in the p r a c t ic a l problems o f in d u s tr ia l h e a l t h , ju s t a s my p r a c t i c e ke e ps me o rie n t e d i n th e pro ble m s o f the d ia g n o s is and tre atm e n t o f lu n g d is e a s e , fo r in th e f i n a l a n a l y s i s i t i s to w ard h e lp i n g th e s e men t h a t a l l our e f f o r t s w ould be d e v o te d . I 4&v d e e p ly a p p r e c ia t e d th e p r i v i l e g e o f w o rkin g unde r y o u r a g i s and the f a i t h yo u have shown i n me i n a llo w i n g me to be go ve rn e d l a r g e l y b y my own judgm e nt i n th e s e l e c t i o n o f the pro bl m a w hich have o c c u p ie d my t i m e . I hope t h a t you w ill fin d that your tru s t has been ju s t ifi e d d e s p ite the d i s c o u r a g i n g ly s m all o u tp u t I may have had so f a r . I s t r o n g l y f e e l t h a t I how know e n o ugh, a nd th e pro ble m s I have s tu d ie d show pro m is e e n o u gh , to have i t w o rth my w h ile to c o n t in u e in c lin ic a l in v e s tig a tio n . I cannot think o f a po ssible a lt e r n a t iv e io w orking he re th a t would anywhere ne ar meet i t s a d v a n ta ge s to me. Whe the r i t w ould be w o rth i t to yo u i s n o t fo r me to d e c i d e . No m a tte r how i t t u rn s o u t , th e re w i l l c e r t a i n l y be no q u e s t i o n i n my mind o f yo ur d e v o tio n t o yo ur i d e a l s w hich have come s o c lo s e t o r e a l i z a t i o n , and o f my in d e b te d n e s s to yo u fo r what 1 have le a rn e d unde r your d ir e c tio n and fo r the w ho le -he arte d support I have always re ce iv e d . / ,/ 1 00028