1 This i s D r . Olch of t h e N a t i o n a l L i b r a r y of Medicine, v i s i t i n g i n t h e o f f i c e of D r . Donald Dexter Van Slyke a t Brookhaven N a t i o n a l Labora- tories. The d a t e i s May 2 7 , 1969. We a r e g o i n g t o b e g i n most inform- a l l y , discussing Dr. Van Slyke s childhood and e a r l y e d u c a t i o n . I do know, and t h a t ' s a b o u t t h e l i m t of i t , s i r , t h a t you were b o r n i n Pike, N e w York. D r . V.: That's right. A t t h e time o f my b i r t h , my f a t h e r w a s a n i n s t r u c t o r i n c h e m i s t r y a t t h e U n i v e r s i t y of Michigan. It happened t h a t my mother w a s s t a y i n g w i t h h i s p a r e n t s i n t h e town o f P i k e when I a r r i v e d on t h e s c e n e . I d o n ' t know why i t w a s p a r t i c u l a r l y c o n v e n i e n t f o r h e r t o b e t h e r e , b u t t h a t was t h e way i t happened. So my b i r t h - p l a c e was P i k e , N e w York. The o l d name w a s Pike H o l l o w because i t w a s i n t h e v a l l e y between two r a t h e r h i g h h i l l s . It was a v i l l a g e of a few hundred p e o p l e on one o f t h e main wagon r o a d s between B u f f a l o and New York, and was r a t h e r a c t i v e i n e a r l y days. It had s a l o o n s where d r i v e r s would g e t c o m f o r t a b l y drunk. It had a small r i v e r which was used f o r water power t o r u n a woolen m i l l and a g r i s t m i l l , and provided a m i l l - pond which was good f o r swimming. Dr. 0.: You were b o r n t h e r e , b u t d i d you a c t u a l l y l i v e t h e r e a w h i l e ? You sound as though you s p e n t a f a i r amount of time t h e r e i n y o u r childhood. D r . V.: L a t e r I went back when I w a s a b o u t f i v e y e a r s o l d . I w e n t , of course, w i t h my p a r e n t s t o Ann Arbor and was t h e r e u n t i l I was two y e a r s 3 g e t t h e cows, and come back. I missed t h e a n i m a l s when w e went t o Ann Arbor, b u t a f t e r a l i t t l e w h i l e I n o t i c e d t h a t t h e r e was a d u p l i c a t e of t h i s c a t a t t h e house n e x t door and I made f r i e n d s w i t h him and was v e r y happy. W e l l , t h e r e w a s a g i r l m e d i c a l s t u d e n t l i v i n g i n t h e same house where we l i v e d . I became f r i e n d l y w i t h h e r and i n t r o d u c e d h e r t o t h i s c a t , whose name was "Harry." I n t h e M e d i c a l School a t t h a t t i m e , t h e r e was a j a n i t o r who was a n o l d p i r a t e , and a l l t h e c h i l d r e n i n Ann Arbor knew t h a t i f h e c o u l d c a t c h you t h e y ' d t a k e you i n and d i s s e c t you! So i t was a g r e a t game t o s t a r t r u n n i n g when you came by t h e Medical School and r u n u n t i l you g o t p a s t ! W e l l , t h i s g i r l medical s t u d e n t suggested t h a t I i n t r o d u c e h e r t o "Harry," so one day I brought him o v e r and gave him a p r o p e r i n t r o d u c t i o n and s h e gave me a n i c k e l t o go o u t and buy a bag of p e a n u t s . When I came back I s a w t h e most h o r r i b l e s i g h t t h a t e v e r came i n t o my l i f e and I h a v e n ' t f o r g o t t e n i t y e t . T h i s o l d p i r a t e was t h e r e w i t h a b i g s a c k and "Harry" was b e i n g poured i n t o i t , head f i r s t , t o be t a k e n o v e r and d i s s e c t e d ! And I begged t h a t "Harry" be r e l e a s e d but t h i s m e d i c a l s t u d e n t was adamant. A l l s h e had t o s a y w a s s h e was s o r r y I g o t back s o soon! I f I saw h e r today I would h a t e her! But a f t e r w a r d s , I met o t h e r g i r l m e d i c a l s t u d e n t s t h a t t a u g h t me t h a t s h e was n o t a f a i r sample! Well we were one y e a r i n Ann Arbor and t h e n my f a t h e r went t o the Johns Hopk ns t o do some p o s t g r a d u a t e work w i t h I r a Remsen, and d u r i n g t h a t y e a r I went back t o l i v e w i t h my u n c l e and a u n t on a farm which was t h r e e m i l e s from P i k e , so I g o t i n c o n t a c t w i t h Pike a g a i n . Then f a t h e r became c h e m i s t a t t h e New York S t a t e Experiment S t a t i o n a t Geneva. 4 D r . 0.: T h a t ' s what I was t h i n k i n g of p r e v i o u s l y , D r . V.: So I j o i n e d him a g a i n and grew up i n Geneva, which was a d e l i g h t f u l town. It had a v e r y good h i g h s c h o o l w i t h e x c e l l e n t t e a c h e r s . There were no j u n i o r d i s t u r b a n c e s i n t h o s e days! Dr. 0.: Were t h e r e any p a r t i c u l a r t e a c h e r s i n h i g h s c h o o l you t h i n k t h a t had any major r o l e i n your e d u c a t i o n ? D r . V.: Yes t h e r e were. There were two. They were b o t h women and they were b o t h e l d e r l y women. One of them w a s M i s s Hancock who was i n charge of the boys. There were 100 boys i n h i g h s c h o o l and when t h e y were n o t r e c i t i n g i n t h e s i d e rooms t h e y were a l l t h e r e t o g e t h e r under h e r s u p e r v i s i o n and s h e k e p t p e r f e c t o r d e r i n t h a t room. She was a powerful and benign p e r s o n a l i t y . She knew a l l o f t h o s e boys. If there was a n y t h i n g t h a t happened t h a t w a s o u t of o r d e r s h e would know what w a s going on immediately and i t would be c o r r e c t e d . Once i n a w h i l e whe would c a l l a boy up and have a n i c e l i t t l e t a l k w i t h him a b o u t something t h a t she thought would be p r o f i t a b l e t o him. O c c a s i o n a l l y s h e would t a l k about t h i n g s t h a t were n o t mathematics--she t a u g h t mathematics. I remem- ber p a r t i c u l a r l y once s h e spoke a b o u t t h e nude i n a r t , and s h e s a i d t h e e n t i r e body e x p r e s s e s moods and f e e l i n g s . And she spoke a b o u t a nude t h a t e x p r e s s e d d e p r e s s i o n and how, as a matter of f a c t , t h e bend i n t h e f o o t seemed t o e x p r e s s i t more t h a n any o t h e r p a r t . She spoke a b o u t t h i s famous s t a t u e of Laacoan and h i s two s o n s , and s h e s a i d t h e agony was expressed t h e r e i n t h e i n t e n s i t y o f t h e abdominal muscles. 5 D r . 0.: S o r t o f a remarkable i n s i g h t b e i n g e x p r e s s e d t o a group of high s c h o o l s t u d e n t s , i s n ' t i t ? Dr. V.: Yes. She h a d a n i c e s e n s e of humor. There was one boy t h a t had a good head b u t h e was l a z y and i n a l g e b r a when we had a h a r d l e s s o n he was l i k e l y t o be home s i c k . One day we came t o a r a t h e r h a r d p a r t and he d i d n ' t show up. The n e x t day he d i d show up and s h e s a i d , "Well, Vrooma n he came from a n o l d Dutch f a m i l y , Vrooman), how d i d you g e t on w i t h t h e l e s s o n yesterda.y?" "Yes," h e s a i d , " I ' v e done a l l t h o s e problems 'I and h e had them a l l worked o u t . And s h e s a i d , "Vrooman, i f we meet twenty y e a r s from now, w e ' l l have something t o t a l k about!" (Laughter) The o t h e r t e a c h e r was a M i s s F l o r e n c e Parker. She had a s i m i l a r , you might c a l l i t a d m i n i s t r a t i v e , p o s i t i o n i n c h a r g e o f t h e g i r l s s i d e of t h e h i g h s c h o o l - - b u t s h e t a u g h t E n g l i s h and s h e w a s e t t e r t h a n any E n g l i s h t e a c h e r I had i n c o l l e g e . She t a u g h t t h e r u e s o f grammar and how t h e E n g l i s h s e n t e n c e was formed and how you shou d e x p r e s s y o u r s e l f i n a way t h a t would b e c l e a r t o t h e p a r t i c u l a r p e o p l e who would r e a d what you were w r i t i n g . I t h i n k t h e f a c t t h a t I have been c o n s i d e r e d a f a i r l y l u c i d w r i t e r i n s c i e n t i f i c work h a s been t o a v e r y l a r g e e x t e n t due t o what Miss P a r k e r t a u g h t me. She e v e n t u a l l y r e t i r e d a n d I went back t o s e e h e r e v e r y y e a r when I ' d be back i n Geneva--I'd go b a c k t o v i s i t my stepmother. When M i s s P a r k e r was n i n e t y t h e r e was a g r e a t c e l e b r a t i o n i n Geneva and s h e had g r e e t i n g s from a g r e a t many i m p o r t a n t people, I t h i n k including t h e President. She l i v e d t o b e 103! I saw 7 a n a l y t i c a l c h e m i s t r y which w a s a g r e a t advantage. D r . 0.: I ' m s u r e t h i s was. D r . V.: I e x p e c t e d t o go i n t o a g r i c u l t u r a l c h e m i s t r y which was my father's line. H e w a s s o r t o f t h e Dean of A g r i c u l t u r a l Chemists i n h i s day. He w a s t h i r t y - n i n e y e a r s i n t h e Geneva A g r i c u l t u r a l E x p e r i - ment S t a t i o n . D r . 0.: He a l s o had r e c e i v e d h i s t r a i n i n g i n c h e m i s t r y a t Ann Arbor, is t h i s r i g h t ? D r . V.: Yes. So b e s i d e s c h e m i s t r y I t o o k b a c t e r i o l o g y and p l a n t phys- i o l o g y a s minors f o r my d o c t o r ' s d e g r e e . I s t a y e d on i n Ann Arbor a f t e r I t o o k my b a c h e l o r ' s d e g r e e and t o o k my d o c t o r ' s d e g r e e a l s o t h e r e . Then I t o o k a c o m p e t i t i v e e x a m i n a t i o n f o r a p o s i t i o n i n Washington i n t h e Bureau o f Chemistry and won i t and was e n r o l l e d among t h e government employees and e x p e c t e d t o go t h e r e r i g h t a f t e r commencement i n 1907. It happened a t t h e s p r i n g meeting of t h e American Chemical S o c i e t y t h a t y e a r , my f a t h e r s a t n e x t t o P. A. Levene who was chemist a t t h e newly started Rockefeller I n s t i t u t e . They g o t t o t a l k i n g a b o u t how t h e r e was so much more demand f o r w e l l - t r a i n e d c h e m i s t s t h a n t h e r e were a v a i l a b l e f o r r e s e a r c h work and my f a t h e r mentioned t h e f a c t t h a t I w a s t a k i n g my degree a t Michigan t h a t time and t h e r e were v a r i o u s p o s i t i o n s I cou d have had and Levene asked i f I ' d be i n t e r e s t e d i n coming t o t h e Rocke- feller. A s a r e s u l t , I g o t a l e t t e r from D r . F l e x n e r , who w a s t h e head o f t h e I n s t i t u t e , i n v i t i n g me t o come t o New York f o r a n i n t e r v i e w . Well, t h e R o c k e f e l l e r I n s t i t u t e had j u s t g o t t e n s t a r t e d , i t d i d n ' t 8 amount t o a n y t h i n g and t h e government was a b i g t h i n g . I d i d n ' t have the s l i g h t e s t i d e a of t a k i n g a j o b w i t h t h e R o c k e f e l l e r and g i v i n g up t h e government o n e , b u t h e r e was a chance f o r a t r i p t o New York w i t h expenses paid! (Laughter) D r . 0.: L i t t l e d i d you know! D r . V.: And so I went down and i t happened Levene was away a t t h e t i m e , but I had a long t a l k w i t h F l e x n e r and h e t o l d me what w a s t h e p r o b a b l e f u t u r e of t h e I n s t i t u t e . On t h e way back t o Ann Arbor I s t o p p e d a t Geneva and t a l k e d i t o v e r w i t h my f a t h e r and t h e r e s u l t o f i t w a s t h a t I r e s i g n e d t h e j o b w i t h t h e government b e f o r e I e v e r went t h e r e and t o o k t h e p o s i t i o n w i t h Levene. So t h a t s h i f t e d my g e n e r a l f i e l d i n s o f a r as i t was a p p l i e d c h e m i s t r y from a g r i c u l t u r a l c h e m i s t r y t o medical c h e m i s t r y . I worked w i t h Levene f o r s e v e n years--worked i n h i s d e p a r t m e n t , worked on p r o t e i n s and amino a c i d s , and i t was a marvelous t i m e working w i t h Levene. He a r r a n g e d f o r me t o go o v e r , i n 1911, t o B e r l i n t o work f o r a y e a r w i t h E m i l F i s c h e r who was t h e g r e a t "sun and god'' of o r g a n i c c h e m i s t r y a s long a s he l i v e d . There was no doubt t h a t E m i l F i s c h e r w a s t h e number one man of t h a t world. I had a chance t o s e e how h e worked. He g o t i n t e r e s t e d a t one t i m e i n t h e problem h e gave m e and had m e go i n t o h i s p r i v a t e l a b o r a t o r y and work r i g h t b e s i d e him f o r t h r e e o r f o u r days. D r . 0.: For h e a v e n ' s s a k e s . T h i s w a s q u i t e a n honor i n t h o s e d a y s , I ' m s u r e , because a p r o f e s s o r ' s p r i v a t e l a b o r a t o r y was g e n e r a l l y o f f - bounds f o r t h e f e l l o w s . 9 D r . V.: Oh, v e r y much. E v e r y t h i n g he d i d was i n a q u a n t i t a t i v e way. That is, i f h e were going t o do t h e s o l u b i l i t y on a new compound, i n s t e a d of j u s t p u t t i n g some of i t i n t o a t e s t t u b e w i t h e t h e r o r c h l o - roform o r whatever i t was t o s e e w h e t h e r i t d i s s o l v e d o r n o t , h e ' d t a k e so many m i l l i g r a m s of i t and m i x i t w i t h so many ccs., h e ' d have a n approximately q u a n t i t a t i v e i d e a of how s o l u b l e i t was. I had a n uncom- f o r t a b l e f i v e minutes once when I was w i t h F i s c h e r . I w a s making a compound t h a t r e q u i r e d t h e u s e of bomb t u b e s - - t h e y ' r e g l a s s t u b e s , heavy g l a s s t u b e s t h a t you s e a l w i t h t h e s u b s t a n c e t h a t you want t o h e a t up under p r e s s u r e . Then you p u t i t i n t o a bomb f u r n a c e - - i t ' s a n i r o n furnace w i t h i r o n t u b e s t h a t w i l l t a k e t h i s bomb tube and i t ' s s o s t r o n g t h a t i f y o u r bomb t u b e blows up it w i l l be c o n t a i n e d . You h e a t t h i n g s up way above t h e b o i l i n g p o i n t s of w h a t e v e r l i q u i d s you use. Well, I was u s i n g t h e s e bomb t u b e s t o make a compound t h a t we were u s i n g f o r t h e work t h a t I w a s s t a r t i n g . D r . 0.: These a r e s p e l l e d bomb, b-o-m-b? D r . V.: B-o-m-b, yes. The F i r s t Chemical I n s t i t u t e ( i t was d e s i g n e d by F i s c h e r ) had a room f o r bomb t u b e s and o t h e r t h i n g s t h a t were l i k e l y t o blow up. T h e r e w a s one p a r t i c u l a r bomb f u r n a c e t h a t was unique. It had c r u d e m i n e r a l o i l i n i t t h a t w a s a m i x t u r e of k e r o s e n e , g a s o l i n e and heavy o i l , j u s t as you g e t i t , t h a t b o i l e d up around t h e chamber t h a t held these tubes. There was a r e f l e x condenser up above and i t was arranged s o t h a t you s t a r t e d b u r n e r s under t h i s t h i n g and a r r a n g e d your r e f l e x condenser so t h a t t h e g a s o l i n e and k e r o s e n e and so f o r t h t h a t b o i l e d up i n t o i t would be d i s c a r d e d u n t i l you g o t t o t h e b o i l i n g p o i n t 10 you wanted and t h e n you f i x e d i t so t h a t t h e c o n d e n s a t e would be r e t u r n e d and t h e m i x t u r e c o n t i n u e b o i l i n g a t t h a t p o i n t , s o yr1-i c o u l d s e t t h e f u r n a c e f o r any t e m p e r a t u r e up t o maybe 200 c e n t i g r a d e . I was using t h a t . There were t h r e e b u r n e r s and one o f them would keep it going a t t h e r i g h t t e m p e r a t u r e and not t o o r a p i d l y t o p r e v e n t a l l of i t g e t t i n g condensed. The condenser w a s o n l y a b o u t a f o o t long. One morn- i n g I went down and p u t t h e t u b e s i n and s t a r t e d a l l t h r e e b u r n e r s i n o r d e r t o g e t i t warmed q u i c k l y , i n t e n d i n g t o go down a f t e r f i v e minutes and t u r n two of them o f f because t h e t h r e e of themwould s t a r t p o u r i n g g a s o l i n e vapor i n t o t h e a i r . I r e t u r n e d t o t h e main l a b o r a t o r y , i n t e n d - ing t o s t a y t h e r e o n l y f o r a moment b e f o r e going back t o t h e bomb room t o t u r n o f f two b u r n e r s . When I g o t up t o my d e s k , F i s c h e r came i n and came s t r a i g h t t o m e and s t a r t e d t a l k i n g . O r d i n a r i l y he never came i n i n t h e morning. He always t o o k a nap a f t e r lunch and came i n a b o u t two o ' c l o c k i n the a f t e r n o o n , b u t t h i s morning he came r i g h t i n . And I s t o o d t h e r e and w a s as s h o r t as I c o u l d be i n my a n s w e r s , b u t you d i d n ' t t e l l "Excellenz" F i s c h e r , "I've g o t t o h u r r y ; you come back some o t h e r time!" (Laughter) I s t o o d t h e r e wondering w h e t h e r t h e b u i l d i n g w a s going t o blow up o r what t h e d e v i l I would do, and f i n a l l y he s a i d , "Ja!" and he walked o f f . I went down and opened t h e door of t h e bomb room. That room was so f u l l of b l a c k s o o t t h a t I c o u l d n ' t s e e t h e windows on t h e other side: The g a s o l i n e had b o i l e d o u t and had c a u g h t f i r e , b u t i t h a d n ' t exploded. It had j u s t q u i e t l y c a u g h t f i r e and i t was b u r n i n g and t h e r e was a flame a yard h gh. I went o v e r and t u r n e d i t o u t . It w a s f o r t u n a t e t h a t I w a s n ' t i n t h e r e when t h e v a p o r s i g n i t e d because t h a t w o u l d n ' t have b e e n so good I d o n ' t t h i n k that people i n t h e F i r s t 11 Chemical I n s t i t u t e ever d i d know how t h a t room happened t o b e so b l a c k t h a t day! D r . 0.: They must have t h o u g h t somebody was smoking kymograph drums o r something i n t h e i r f a c i l i t i e s ! How c o u l d one r e a l l y compare perhaps Gomberg, Levene and F i s c h e r a s c h e m i s t s ? Did t h e y have any s i m i l a r i t i e s ? D r . V.: Well, t h e i r p e r s o n a l i t i e s were v e r y d i f f e r e n t . F i s c h e r was a man of t e r r i f i c power. I f he had gone i n t o p o l i t i c s h e would have b e e n a n o t h e r Bismarck! He w a s a b i g man--he w a s a b o u t 60 when I worked w i t h him--his handshake was l i k e a n e l e c t r i c shock then: He looked l i k e a t y p i c a l German p r o f e s s o r ; he had a beard. But he was a man of t e r r i f i c force. I w a s t o l d t h a t i n h i s e a r l i e r days h e ' d had a t e r r i f i c temper when t h i n g s went wrong. I n e v e r saw i t b u t once. He s t a r t e d me on a problem and I had t o make some c r y s t a l l i n e material t o s t a r t i t o u t w i t h and we had some d i f f i c u l t y u n t i l f i n a l l y I s a w a method i n t h e l i t e r a - t u r e f o r making i t . I got a p l a t e f u l of b e a u t i f u l c r y s t a l s . When he came i n I s t a r t e d t o show them t o him, b u t he s a i d , "Schon gemacht;" a l r e a d y made! He s a i d t h a t t h e two Englishmen t h a t b u t t e d i n o n t h i s problem had done j u s t what we were i n t e n d i n g t o do. He "panthered" up and down f o r a b o u t f i v e minutes and t h e n went o u t : D r . 0.: Was he t h e e g o t s t t h a t Warburg a p p a r e n t l y w a s ? D r . V. : W e l l , I wouldn' s a y he was a n e g o t i s t . He was a g r e a t man; he knew i t b u t h e was i n f o r m a l . With r e g a r d t o t h i s i n c i d e n t , t h e r e w a s a S a t u r d a y morning c o l l o q u i u m a t 1 1 : O O where everybody t h a t had a doc- t o r ' s degree w e n t . A t t h e n e x t one F i s c h e r reviewed t h i s p a p e r t h a t 12 t h e s e two Englishmen had done and reviewed i t v e r y f a i r l y , and h e s a i d t h a t he and I had s t a r t e d on it b u t t h a t t h e y had had t h e same i d e a and he was s u r e t h a t t h e i r s o l u t i o n of i t was c o r r e c t . H i s f i r s t reaction was t o b o i l over! But h e was a g r e a t human being. He more o r less r i d i c u l e d t h e s u p e r f o r m a l t y p e of German o f f i c i a l ; h e w a s a r e a l man. F i s c h e r was a w a r m i n d i v i d u a l . He had a nephew named Gerlach t h a t was a l s o working w i t h him--and he p u t G e r l a c h a t t h e same d e s k w i t h me. (The desks were a b o u t e i g h t f e e t l o n g and t h e r e would be two men working a t each.) G e r l a c h and I became v e r y good f r i e n d s . G e r l a c h had t a k e n h i s d o c t o r ' s degree a t Erlangen University. Most o f t h e men t h a t worked w i t h F i s c h e r a l r e a d y had t h e i r d o c t o r ' s d e g r e e . Some of them were f o r e i g n e r s , b u t t h i s boy came from B a v a r i a and he f e l t a s much a f o r e i g n e r i n P r u s s i a a s I was. He was homesick f o r Bavaria! I had j u s t come t o B e r l i n w i t h my w i f e , who had been a s t u d e n t i n t h e U n i v e r s i t y of Michi- gan, and we became v e r y good f r i e n d s w i t h G e r l a c h and went around together evenings a g r e a t d e a l . Fischer was t e r r i f i c a l l y strict with Gerlach. It was v e r y d i f f i c u l t f o r G e r l a c h t o do a n y t h i n g t h a t was r i g h t ! Weekends F i s c h e r would t a k e Gerlach t o h i s v i l l a o u t a t Wannsee, a l a k e o u t s i d e of B e r l i n , and t r e a t him l i k e a s o n , b u t rather t h a n show him any f a v o r i t i s m i n t h e l a b o r a t o r y h e l e a n e d o v e r backwards and w a s h a r d on t h e poor boy: W h i t s u n t i d e s p r i n g t i m e came and everybody had a few days v a c a t i o n . They make much more of i t t h e r e t h a n w e do h e r e . The v a c a t i o n s t a r t e d o n a S a t u r d a y morning, b u t G e r l a c h was so homesick t o g e t back t o Bavaria t h a t he wanted t o g e t a t r a i n F r i d a y a f t e r n o o n . He was working w i t h a b i g p o r c e l a i n d i s h i n which he w a s b o i l i n g some 13 stuff with lead oxide i n order t o p r e c i p i t a t e chloride. It w a s sup- posed t o make l e a d o x i c h l o r i d e which e v e n t u a l l y would p r e c i p i t a t e a l l the c h l o r i n e . It t a k e s b o i l i n g a l o n g time because l e a d c h l o r i d e i s f a i r l y s o l u b l e ; i t ' s t h e s l o w l y formed o x i c h l o r i d e t h a t i s p r e c i p i t a t e d . And F i s c h e r t o l d him t o p r e c i p i t a t e t h e c h l o r i d e w i t h l e a d o x i d e i n s t e a d of s i l v e r , I d o n ' t know why b u t he d i d . G e r l a c h would b o i l i t and b o i l it and t a k e a d r o p o u t i n a p i p e t t e and t e s t i t w i t h s i l v e r n i t r a t e f o r c h l o r i d e and t h e r e ' d be a p r e c i p i t a t e and h e ' d b o i l i t , p u t i n some water and b o i l i t a g a i n . W e l l , h e ' d b o i l e d i t a l l the morning and t k r e was s t i l l c h l o r i d e i n it and h e wanted t o g e t h i s t r a i n i n t h e a f t e r n o o n and he knew F i s c h e r would be coming i n as u s u a l a b o u t 2 o ' c l o c k so he s a i d , "I do want t o make t h i s t r a i n , w o n ' t you b o i l t h i s d i s h f o r me and i f t h e "geheimrat" comes i n h e ' l l s e e i t b o i l i n g and h e ' l l t h i n k t h a t I ' m somewhere i n one o f t h e o t h e r rooms and t h a t I h a v e n ' t r u n away!" So a f t e r l u n c h I s t a r t e d i t b o i l i n g and when it b o i l e d down a l i t t l e b i t I p u t a l i t t l e w a t e r i n and a l l t h e o t h e r men--a dozen o f them working i n t h i s room--one a f t e r t h e o t h e r , t h e y g o t o n t o what was g o i n g on. An I t a l i a n was behind me and he would come and pour a l i t t l e w a t e r i n and then s m i l e and t h e German t h a t was next t o him would come o v e r and pour a l i t t l e w a t e r i n and s m i l e and walk away! And t h e n o t h e r s took t h e i r turn. W e l l , s u r e enough 2 o ' c l o c k i n t h e a f t e r n o o n i n comes "geheimrat" and you could have h e a r d a p i n drop! He came s t r a i g h t t o my d e s k - - r i g h t next t o G e r l a c h ' s - - a n d he went t o t h e d i s h and p i c k e d up a p i p e t t e and took o u t a drop and t e s t e d it and t h e r e was s t i l l c h l o r i d e i n i t , and he l a i d i t down and walked o f f w i t h o u t a word. And t h e n everybody began i n t h i s s p e c i a l room. One o f his t e a c h i n g a s s i s - we worked t o g e t h e r . a s t y e a r b e f o r e I t o o k my d o c t o r ' s d e g r e e , t o a g i r l s o t a k i n g c h e m i s t r y ; a very charming g i r l . She was 15 a f t e r w a r d s , Gomberg s a i d , ' v e l 1 1 f l i p a c o i n and i f i t ' s h e a d s s h e goes out w i t h the crowd!" W e l l , i t t u r n e d o u t h e a d s and Gomberg s a i d , "We f l i p again.'' (Laughter) So s h e worked i n t h e same room w i t h me t h a t y e a r and t h a t w a s v e r y p l e a s a n t . One time I needed a t w o - l i t e r b o t t l e . The o n l y one I cou d f i n d w a s one t h a t had been used f o r making anhydrous e t h e r by p u t t ng m e t a l l i c sodium i n i t . T h a t ' s t h e way you make p e r f e c t l y anhydrous e t h e r ; t h e sodium h a s t e r r i f i c a f f i n i t y f o r water and i t w i l l t a k e a n y water o u t of t h e e t h e r . Well, i f you p u t m e t a l l i c sodium i n t o w a t e r it e x p l o d e s like a firecracker: This b o t t l e had been used f o r e t h e r , and I knew i t , b u t i t had been s t a n d i n g w i t h t h e s e p i e c e s o f sodium i n t h e bottom f o r apparently years. The sodium had t a k e n up w a t e r and c a r b o n a t e i n t h e a i r and t h e s e p i e c e s were a l l c r u s t e d . So I t h o u g h t t h a t p r o b a b l y t h e r e was no sodium l e f t , b u t I knew t h e r e might be some, so I t u r n e d t h e w a t e r o n i n t h e s i n k , dumped t h e p i e c e s i n t o i t , and s t e p p e d back t o s e e whether a n y t h i n g happened. F l a s h e s went o f f l i k e cannon f i r e - c r a c k e r s and when i t s t o p p e d , Gomberg looked i n through h i s door and he s a i d , "Now Van S l y k e , you know what m e t a l l i c sodium and water makes." (Laughter) I worked r i g h t n e x t t o him. Anytime I had a n y t h i n g t o t a l k about h e w a s r i g h t t h e r e . Those were days when y o u r p r o f e s s o r w a s n o t a t a distance. D r . 0.: Yes, t h a t ' s s o t r u e . I imagine t h e r e a r e some i n s t a n c e s where i t ' s s t i l l t h i s way, b u t c e r t a i n l y n o t a t some l e v e l s . D r . V.: T h e r e are so many g r a d u a t e s t u d e n t s now t h a t t h e y c a n ' t have t h a t intimacy. I n F i s c h e r ' s p l a c e he had a c e r t a i n number of p l a c e s . 16 He would o n l y t a k e s o many p e o p l e ; a b o u t a dozen. The o n l y r e a s o n I got t o work w i t h him w a s Levene who had worked w i t h him b e f o r e and knew F i s c h e r personally--Levene a r r a n g e d it. I worked w i t h F i s c h e r f o r a semester. B e r l i n w a s a l o v e l y town i n t h o s e days. D r . 0.: T h i s would be 1911? D r . V.: Yes. T h a t w a s b e f o r e World War I. Germany was t h e s c i e n t i f i c c e n t e r of t h e w o r l d . It w a s a t r a g e d y t h a t t h e m i l i t a r y p e o p l e of Germany g o t h e r i n t o t h a t w a r . They were t h e o n l y ones t h a t wanted i t . D r . 0. T h a t would b e t h e p e r i o d t h a t w a s t h e t a i l end of t h e g r e a t m i g r a t on of p h y s i c i a n s t o Germany and A u s t r i a - - - - D r . V.: Physicians, chemists, physicists. I t h i n k p r o b a b l y Germany had more g r e a t s c i e n t i s t s i n p r a c t i c a l l y a l l l i n e s t h a n all t h e r e s t of t h e world. P r a c t i c a l l y e v e r y o u t s t a n d i n g s c i e n t i s t i n t h i s c o u n t r y had had p a r t of h i s t r a i n i n g i n Germany. Levene s p e n t two y e a r s i n Germany. He g r a d u a t e d a t P e t e r s b u r g M i l i t a r y Medical School. H e t h e n came o v e r w i t h h i s f a m i l y from R u s s i a and went i n t o p r i v a t e p r a c t i c e . He g o t t u b e r c u l o s i s , went up t o Saranac and w a s cured. H e d e c i d e d t h a t he could n o t resume t h e l i f e of a p r a c t i c i n g p h y s i c i a n , and d e c i d e d t o go into biochemistry. H e went abroad and worked f o r two y e a r s . P a r t of i t was w i t h F i s c h e r . He came back and w a s e v e n t u a l l y p i c k e d up by Flexner t o s t a r t t h e R o c k e f e l l e r I n s t i t u t e . When t h e I n s t i t u t e s t a r t e d , t h e s e n i o r men w e r e , w i t h t h e e x c e p t i o n of Opie, were men who f o r one r e a s o n o r a n o t h e r would n o t be l i k e l y t o be c a l l e d t o p r o f e s s o r s h i p s i n American u n i v e r s i t i e s . D r . 0.: Why is t h a t ? D r . V.: Because t h e y were f o r e i g n e r s ! There w a s Levene who w a s a Russian. H e d i d n ' t know anybody i n American m e d i c a l s c h o o l s ; he had no p o l i t i c a l r o u t e , so t o speak. And t h e n t h e r e w a s C a r r e l , a French- man, and a s u r g e o n - - e x p e r i m e n t a l surgery--who g o t t h e Nobel P r i z e f o r a t e c h n i q u e he worked o u t f o r s u t u r i n g blood v e s s e l s . Then t h e r e w a s D r . M e l t z e r who was a German from Riga, which had been p a r t of R u s s i a . But t h e c u l t u r a l p a r t of Riga w a s German. It was one of t h e B a l t i c towns. He came o v e r t o t h i s c o u n t r y and went i n t o p r i v a t e p r a c t i c e and a l s o c o n t i n u e d t o do some p h y s i o l o g y i n h i s own home. D r . 0.: He was p r i m a r i l y a r e s p i r a t o r y p h y s i o l o g i s t , w a s he n o t ? Dr. V.: No, i t was g e n e r a l physiology. The t h i n g he was known f o r was h i s d i s c o v e r y of (I t h i n k he d i s c o v e r e d i t ) , t h e f a c t . t h a t when a muscle c o n t r a c t s , i t s a n t a g o n i s t r e l a x e s , and he worked i t o u t i n s t u d y i n g t h e process of swallowing. And i n Germany h i s common name w a s "Schluck" Meltzer. "Schlucken" means t o swallow. "Schluck" M e l t z e r , because o f that. And t h e n t h e r e was Noguchi, t h e Japanese, who n a i l e d t h e s y p h i l i s s p i r o c h e t e a s t h e c a u s e of s o f t e n i n g of t h e b r a i n . W e l l , F l e x n e r was keen enough t o s e e t h e p o s s i b i l i t i e s of t h e s e men, and t h e y were t h e men that the I n s t i t u t e started with. Opie, who had come from Hopkins, w a s t h e one man t h a t had background i n American u n i v e r s i t i e s and would be l i k e l y t o g e t a p r o f e s s o r s h i p and he o n l y s t a y e d a t the R o c k e f e l l e r two o r t h r e e y e a r s , t h e n t o o k a p r o f e s s o r s h i p i n S t . Louis. 18 Dr. 0.: Yes, Washington U n i v e r s i t y . D r . V.: Yes. But t h a t ' s t h e way t h e I n s t i t u t e s t a r t e d ; i t w a s s o r t of a menagerie. D r . 0.: I g a t h e r D r . F l e x n e r was r e a l l y q u i t e a good j u d g e of men, a l t h o u g h h e may have had some h e l p from p e o p l e l i k e Welch a n d o t h e r s . D r . V.: It was F l e x n e r ' s keenness of judgment. The I n s t i t u t e was what he made i t . He g o t h i s men and t h e n h e backed them up and h e p e r s o n - a l l y handled t h e I n s t i t u t e . F o r example, I w a s w i t h Levene s e v e n y e a r s , then t h e I n s t i t u t e b u i l t a h o s p i t a l and Levene and F l e x n e r a p p a r e n t l y t a l k e d i t o v e r and d e c i d e d t h a t I s h o u l d be moved o v e r i n t o t h e H o s p i t a l and develop a department of c h e m i s t r y i n t h e H o s p i t a l . D r . 0.: With t h e e x p r e s s i d e a being t h a though you would s t i l l b e a b l e to c o n t i n u e , t o u s e a hackneyed p h r a s e , n " b a s i c c h e m i s t r y " you would develop a department r e l a t e d t o c l i n i c a l c h e m i s t r y . D r . V.: Yes. It w a s hoped I would t a k e a n i n t e r e s t i n t h a t . I was s o d i s t r u s t f u l of my a b i l i t y t o do t h a t and so r e l u c t a n t a t l e a v i n g Levene, t h a t I made F l e x n e r w r i t e me a l e t t e r s a y i n g t h a t i f I d i d n ' t l i k e i t i n t h e H o s p i t a l I c o u l d go back t o Levene! But I found t h a t t h e young d o c t o r s i n t h e H o s p i t a l were a l l j u s t a b o u t my age and t h e y t o o k me i n . I began t o p i c k up medicine p r e t t y f a s t ; found i t f a s c i n a t i n g . So I s t a y e d i n t h e H o s p i t a l t h e r e s t of t h e t i m e I was a t t h e R o c k e f e l l e r . 19 D r . 0.: One c a n r e a l l y t h e n p u t t h i s d e c i s i o n , i n a s e n s e , i n t h e l a p of Simon F l e x n e r . He's t h e one b a s i c a l l y who d e c i d e d t h a t you were t h e man f o r t h i s p a r t i c u l a r s p o t . D r . V.: Yes. I n t h e H o s p i t a l , i t w a s h a r d work, r i d i n g two h o r s e s , because I d i d n ' t g i v e up my b a s i c work. A t t h e same t i m e , I t o o k up t h e s t u d y of k i d n e y p h y s i o l o g y and k i d n e y d i s e a s e s , b u t t h e young d o c t o r s t h a t were t h e r e d i d n ' t know t h e f i e l d . I had t o l e a r n t h e s t o r y of ne- p h r i t i s and t h e p h y s i o l o g y of t h e k i d n e y and what goes w i t h t h a t from t h e ground up. And, a l t h o u g h I w a s a c h e m i s t , I found myself i n c h a r g e of a ward of p a t i e n t s w i t h B r i g h t ' s d i s e a s e . W e l l , a l t h o u g h I was v e r y husky, a p p a r e n t l y i t t o o k q u i t e a good d e a l o u t of me and a c l i n i c i a n t h a t came t o work w i t h u s f o r a s a b b a t i c a l y e a r , t h a t was Thomas Add S of San F r a n c i s c o , he went o v e r t o F l e x n e r and s a i d , "Van Slyke i s go ng t o g i v e o u t p r e t t y soon u n l e s s you g i v e him a y e a r o f f . " D r . 0.: Add s of t h e Addis Count? Dr. V.: Yes Well, I d i d n ' t f e e l t h a t way, b u t F l e x n e r c a l l e d me o v e r . T h i s i l l u s t r a t e s t h e way F l e x n e r h a n d l e d t h i n g s . He c a l l e d me o v e r t o h i s o f f i c e and he s a t a c r o s s t h e desk--he had p i e r c i n g b l u e eyes--and h e looked a t me f u l l , a s though he was l o o k i n g r i g h t t h r o u g h me, and h e s a i d , "Van S l y k e , g e t y o u r t h i n g s i n o r d e r and g e t o u t o f h e r e and go t o Europe w i t h your f a m i l y f o r a year!" D r . 0.: Gosh, j u s t l i k e t h a t ! D r . V.: Yes. H e s a i d , " I ' m n o t i n v i t i n g you t o do t h i s , t h i s i s a n order:" I f you had a t h i n g t h a t r e q u i r e d a d e c i s i o n , you'd g e t i t from 20 Flexner i n a b o u t t h a t time and i t would be a s good a d e c i s i o n a s c o u l d have been made i f he had s p e n t months on i t . Dr . 0.: What y e a r would t h i s have been t h a t you t o o k t h i s t r i p ? D r . V.: T h a t w a s '29. So t h e f a m i l y and I went t o Europe and we s p e n t the w i n t e r i n Grenoble, i n F r a n c e . My c h i l d r e n , who w e r e i n t h e i r t e e n s , went t o Grenoble U n i v e r s i t y , o r t h e h i g h s c h o o l , and p i c k e d up French and I , i n a l e i s u r e l y way, w r o t e one of the main c h a p t e r s of P e t e r s ' and Van S l y k e ' s Q u a n t i t a t i v e C l i n i c a l Chemistry, w r o t e t h e c h a p t e r on t h e acid-base balance. D r . 0.: So you d i d s t a y o u t o f t h e l a b o r a t o r y f o r t h a t y e a r . D r . V.: Yes. There was no l a b o r a t o r y t o work i n and no a s s i s t a n t s t o be r e s p o n s i b l e f o r . D r . 0.: I ' m t r y i n g t o t h i n k , I s h o u l d know t h i s , b u t I j u s t c a n ' t remember when P e t e r s and Van S l y k e , Q u a n t i t a t i v e C l i n i c a l Chemistry was pub 1i s h e d D r . V.: It came o u t a b o u t 1930. I t h i n k t h e I n t e r p r e t a t i o n s came o u t i n ' 3 0 and t h e Methods i n ' 3 1 . A t l e a s t we s p e n t t e n y e a r s on t h a t . D r . V.: The pub i s h e r s came t o P e t e r s - - P e t e r s worked w i t h m e f o r a y e a r j u s t b e f o r e t h e w a r and t h e n h e went i n t o t h e Army and when h e came o u t he went t o Yale, b u t we k e p t i n c o n t a c t . The p u b l i s h e r s came t o P e t e r s and asked him t o w r i t e a b r i e f manual on c l i n i c a l c h e m i s t r y , and he asked me t o l o o k o v e r h i s c h a p t e r s when he g o t them done. He s e n t 21 me t h e f i r s t c h a p t e r and I went o v e r i t and made changes i n i t and t h e n he s a i d , "I c a n s e e t h a t w e have t o do t h i s t o g e t h e r ; i t t a k e s a c h e m i s t a s w e l l as a n i n t e r n i s t ! " We t h o u g h t we'd do i t i n one v a c a t i o n , b u t i t j u s t grew and we d i d n ' t r e a l i z e how much material t h e r e w a s and i t w a s j u s t a b o u t t e n y e a r s b e f o r e we g o t i t f i n i s h e d . Some c h a p t e r s t o o k a whole year! D r . 0.: I t ' s s t i l l t h e c l a s s i c and e x t r e m e l y d i f f i c u l t t o come by. D r . V.: Oh, I t h i n k i t w a s u s e f u l . D r . 0.: Oh, I t h i n k t h e r e ' s no q u e s t i o n t h a t i t , i n a s e n s e , r e v o l u - t i o n i z e d t h e whole f i e l d a s f a r a s t h e a p p l i c a t i o n of a n a l y t i c a l c h e m i s t r y t o , a g a i n i n q u o t e s " c l i n i c a l medicine." T h i s was one of t h e t h i n g s I ' d l i k e v e r y much t o d w e l l upon f o r a b i t , i f w e might. Perhaps I might j u s t t u r n t h i s over. We're not a t t h e e n d , b u t w e ' r e g e t t i n g c l o s e t o i t and we w o n ' t be i n t e r r u p t e d . [End o f S i d e I , Reel 11 [ S i d e 11, R e e l 11 Recorded May 2 7 , 1969. D r , 0.: I ' m r e a l l y n o t s u r e how t o p h r a s e t h e q u e s t i o n , b u t when you entered the f i e l d of c l i n i c a l biochemistry, I c a l l i t , perhaps unwisely, I ' m not s u r e how you r e a l l y r e f e r t o t h i s b r a n c h , i f you w i l l , of b i o - chemistry. Dr. V.: Well, t h a t ' s a s good a name as any, I g u e s s . 22 D r . 0.: Right. It r e a l l y w a s - - i f i n i t s infancy a t a l l - - j u s t barely i n i t s infancy. The work of y o u r s e l f and y o u r group a t the R o c k e f e l l e r I n s t i t u t e i t seems t o me changed t h e e n t i r e method, i n many ways, o f p r a c t i c i n g medicine. It was o r i g i n a l l y a q u a l i t a t i v e s c i e n c e and t h r o u g h the e f f o r t s of y o u r group i n t h i s tremendously v a s t a r e a a n u n d e r s t a n d i n g of pH and i t s c l i n i c a l i m p l i c a t i o n s and a c i d - b a s e b a l a n c e , e l e c t r o l y t e s , and so on was developed. One ends up i n g o i n g from t h e q u a l i t a t i v e t o r e a l l y a q u a n t i t a t i v e t y p e of medicine. I would imagine, a t t h e o n s e t of your c a r e e r a t t h e R o c k e f e l l e r I n s t i t u t e , what one found as r o u t i n e l a b o r a t o r y s t u d i e s performed on p a t i e n t s were a t o t a l l y d i f f e r e n t " k e t t l e of f i s h " t h a n what t h e y were some 15, 20 y e a r s l a t e r . And r e a l l y , your group i s v e r y much r e s p o n s i b l e f o r a g r e a t d e a l of t h i s . D r . V.: We were r e s p o n s i b l e f o r p a r t o f i t . T h e r e were o t h e r s , of c o u r s e , p a r t i c u l a r l y F o l i n a t Harvard and B e n e d i c t a t C o r n e l 1 Medical School. I t h i n k o u r group a t t h e R o c k e f e l l e r were c l o s e r t o t h e c l i n i c a l a p p l i c a t i o n ; we were working i n a h o s p i t a l . B e n e d i c t was working i n a medical s c h o o l b u t n o t i n a h o s p i t a l . And i t was t h e same w i t h most of the o t h e r biochemists a t t h a t t i m e . Most of t h e b i o c h e m i s t s t h e n were t r a i n e d i n a time when t h e r e was n o t a g r e a t d e a l o f q u a n t i t a t i v e work done. You worked w i t h p r o t e i n s and p e p t o n e s , and so f o r t h . Particularly blood c h e m i s t r y had j u s t s t a r t e d t o develop. We g o t i n t o i t because a t t h e time I moved i n t o t h e H o s p i t a l w i t h my a s s i s t a n t , Glenn C u l l e n , t h e Hospital was s t a r t i n g t o study diabetes. T h a t w a s b e f o r e t h e days o f i n s u l i n , and t h e man who brought d i a b e t e s , s o t o s p e a k , t o t h e Rocke- f e l l e r H o s p i t a l was F. M. A l l e n who had been working on it w i t h dogs. 23 He made dogs d i a b e t i c by c u t t i n g o u t t h r e e - q u a r t e r s of t h e p a n c r e a s . up t o t h a t time t h e t h e o r y of h a n d l i n g d i a b e t i c s was t o g e t them t o e a t a s much f a t a s you c o u l d . They c o u l d n ' t b u r n s u g a r so you f e d them cream and t r i e d t o keep t h e i r s t r e n g t h up by g i v i n g them t h e c a l o r i e s i n fat. A l l e n f e d some of h i s d i a b e t i c dogs a good abundant c a l o r i e d i e t m o s t l y made up o f f a t s , and o t h e r s he p u t on s e m i - s t a r v a t i o n . They were n o t c o m p l e t e l y s t a r v e d b u t t h e y were t h i n , and k e p t t h a t way. Well, the dogs t h a t were w e l l - f e d on c a l o r i e s were f i n e f o r a few months, b u t then t h e i r d i a b e t e s g o t worse and t h e y d i e d w h i l e the t h i n ones l i v e d - - t h e i r diabetes d i d n ' t progress. And A l l e n came t o t h e I n s t i t u t e t o t r y out what came t o be c a l l e d "the s t a r v a t i o n t r e a t m e n t " f o r d i a b e t e s . His p r i n c i p l e w a s t o p u t t h e p a t i e n t on a p r a c t i c a l l y s t a r v a t i o n d i e t . He fed them t h r i c e - c o o k e d v e g e t a b l e s ; t h e y were b o i l e d t h r e e times s o t h e r e was n o t h i n g l e f t b u t b u l k , t o s a t i s f y t h e d e s i r e f o r something i n t h e stomach. And i n a few days t h e y would s t o p e x c r e t i n g s u g a r and t h e blood sugar would come down and t h e n h e ' d s t a r t b u i l d i n g up t h e d i e t t o s e e how much t h e y c o u l d t o l e r a t e . T h a t w a s the o n l y way t h a t a s e v e r e d i a - b e t i c could be k e p t a l i v e u n t i l i n s u l i n came a l o n g . W e l l , t h e danger was t h a t on t h i s a l m o s t no c a l o r i e d i e t , a c i d o s i s c o u l d d e v e l o p v e r y quickly. A l l e n d i d n ' t t h i n k i t c o u l d ; t h e dogs d o n ' t have i t . And h e f i g u r e d t h a t i f you d i d n ' t g i v e them t h e f a t which makes t h e k e t o n e b o d i e s , t h e y c o u l d n ' t make o x y b u t y r i c a c i d and t h e y c o u l d n ' t g e t a c i d o - sis. Well, one of t h e f i r s t p a t i e n t s we had who was p u t on t h i s t r e a t - ment w a s a middle-aged n i c e l a d y t h a t came i n , a t y p i c a l middle-age diabetic, not t e r r i b l y severe. She went i n t o coma and d i e d i n a week! D r . 0.: On t h i s s t a r v a t i o n d i e t ? 24 D r . V.: yes. Something had t o be done t o s e e a c i d o s i s coming b e f o r e it g o t t o o bad because once you go i n t o coma y o u ' r e f i n i s h e d . And so Cullen and I r e a d up a l l t h e l i t e r a t u r e t h e r e was o n a c i d o s i s and d e - cided t h a t t h e b e s t c l i n i c a l metnod would be t o measure t h e plasma b i c a r b o n a t e and t h e most p r a c t i c a l way t o do t h a t a t t h e b e d s i d e w a s g a s o m e t r i c a l l y , and f o r t h a t r e a s o n we developed t h e o l d handshaken C02 machine. Then l a t e r we g o t t o d o i n g more r e f i n e d work on t h e p h y s i c a l chemistry of t h e e l e c t r o l y t e s i n t h e blood and we needed a more a c c u r a t e procedure so w e developed t h e manometric machine. With t h e o l d hand- shaken machine you measured t h e volume of g a s a t b a r o m e t r i c p r e s s u r e . You c a n measure t h e b a r o m e t r i c p r e s s u r e t o a t e n t h of a m i l l i m e t e r which i s about one p a r t i n some e i g h t t h o u s a n d , b u t i n y o u r volume you might have one o r two p e r c e n t e r r o r , p a r t i c u l a r l y i f you had a small volume. To make t h e a c c u r a c y g r e a t e r , t h e s t u n t w a s t o d e c r e a s e the p r e s s u r e and i n c r e a s e t h e volume u n t i l t h e volume e r r o r was brought down t o somewhere near t h e p r e s s u r e e r r o r was. T h a t w a s t h e b a s i s of the manometric appa- ratus. A f t e r w e worked o u t t h e CO2 method we d i d n ' t have any more d e a t h s i n coma because one c o u l d d e t e c t i t by t h e a n a l y s e s w e l l b e f o r e t h e r e were any c l i n i c a l s i g n s . The b i c a r b o n a t e c a n go down t o h a l f normal and t h e p a t i e n t i s n ' t uncomfortable. He may be a l i t t l e dopey, a l i t t l e sleepy. H e ' s b r e a t h i n g more d e e p l y t h a n n o r m a l l y , b u t you wouldn't s e e i t u n l e s s you were used t o l o o k i n g f o r i t because he d o e s n ' t breathe f a s t e r , he j u s t b r e a t h e s a l i t t l e deeper. And t h e n when h e g e t s much below t h a t , t h e n , i n t h o s e days, t h e coma would develop e x p l o s i v e l y . D r . 0.: You a l s o were d e e p l y involved i n s t u d i e s i n r e n a l physiology. 25 D r . V.: W e l l , t h e way we switched t o t h a t was t h a t a f t e r some y e a r s A l l e n l e f t and s t a r t e d a d i a b e t i c r e s e a r c h i n s t i t u t e of h i s own. He had brought t h e d i a b e t i c problem t o t h e H o s p i t a l and t h e D i r e c t o r of the H o s p i t a l t h o u g h t t h a t i t w a s f a i r t o l e t him t a k e it w i t h h i m and not t o compete w i t h him. By t h a t t i m e I had become i n t e r e s t e d i n c l i n - i c a l medicine and d e c i d e d t o t a k e on a n o t h e r problem. I decided t o take o n t h e r e n a l problem because there w a s a chance f o r q u a n t i t a t i v e c h e m i s t r y there--measurement of f u n c t i o n and the m e t a b o l i c t h i n g s t h a t the kidney d i d . So we d e l i b e r a t e l y t o o k on t h e k i d n e y problem. Dr. 0.: Through t h o s e y e a r s c e r t a i n l y a c o n s i d e r a b l e number of c l i n i - c i a n s s p e n t time working i n y o u r l a b o r a t o r y , many of whom went on i n t o be v e r y much b i o c h e m i c a l l y - o r i e n t e d i n t e r n i s t s , i f you w i l l , pro- f e s s o r s i n v a r i o u s departments. D r . V.: Yes, H a s t i n g s counted them up once and he s a i d t h e r e were 7 0 : One of them became P r o f e s s o r of Medicine i n Oslo i n Norway; two o f them became P r o f e s s o r s of Medicine i n Copenhagen. D r . 0.: Did K a i Linderstrdm-Lang work i n y o u r l a b ? D r . V.: No, no, I n e v e r worked w i t h Linderstrdm-Lang and he never worked w i t h me. The Danes t h a t d i d work w i t h me, t h e f i r s t one was Lundsgaard. H e w a s t h e f i r s t man t h a t d i d a blood pH w i t h a hydrogen e l e c t r o d e , and h e showed up one morning w i t h o u t any warning--a b i g , j o l l y fellow. H e had a l r e a d y done so much t h a t h e had a n i n t e r n a t i o n a l r e p u - t a t i o n , I knew h i s name. I came i n one morning and everybody i n t h e l a b o r a t o r y - - 1 was a l i t t l e late--was down i n my o f f i c e h a v i n g a v e r y 26 good t i m e and n o t d o i n g a n y work. I went down and h e r e was t h i s b i g chap l e a n i n g back a g a i n s t t h e bench e n t e r t a i n i n g t h e crowd, and he looked a t me and he s a i d , "Uh, you Van Slyke?" I s a i d , "Yes." He s a i d , " w e l l , I'm Lundsgaard, I ' v e come t o work w i t h you f o r a year!" H e had decided h e would do t h a t and went down t o t h e Danish s h i p p i n g company and s a i d t h a t h e wanted them t o g i v e him a j o b a s s h i p ' s s u r g e o n t o g e t over t o New York. He was t h e k i n d of f e l l o w t h a t g o t a n y t h i n g h e asked for! Well, we worked t o g e t h e r s e v e n y e a r s , and t h e n h e went back and became P r o f e s s o r of Medicine i n t h e U n i v e r s i t y o f Copenhagen. He w a s so i n t e r e s t e d i n t h e t e c h n i q u e s t h a t we had worked o u t t h a t he a r r a n g e d t o have C u l l e n , who w a s my a s s i s t a n t , go o v e r there and work t h e r e i n h i s c l i n i c f o r a y e a r t o i n t r o d u c e methods. Then l a t e r S a l v e s e n , who was w t h me s e v e r a l y e a r s became P r o f e s s o r of Medicine i n Oslo. He's t h e k ng's physician a t present! And t h e n t h e r e w a s Eggert M d l l e r who d i d a l o t of t h e k i d n e y work. He's j u s t r e t i r e d from t h e P r o f e s s o r s h i p o f Medicine a t Copenhagen. D r . 0.: W e l l , I know i t ' s q u i t e a n army--a l e g i o n o f p e o p l e . How was your l a b o r a t o r y b a s i c a l l y o r g a n i z e d when you'd have p e o p l e l i k e D r . Hastings there o r Dr. Cullen? Was t h e r e s o r t of a common problem t h a t t h e e n t i r e l a b o r a t o r y s t a f f was working on o r d i d e a c h man have h i s own p a r t o f a common problem? Were you t h e r e as t h e "geheimrat"? Was it l i k e F i s c h e r ' s l a b o r a t o r y where t h e s e p e o p l e were working on a project p r i m a r i l y o f i n t e r e s t t o F i s c h e r ? D r . V.: Yes, e a c h man t h e r e worked o n a problem. They a l l r a d i a t e d from F i s c h e r , s o t o speak. I f a man came t o work w i t h me, he u s u a l l y wanted 27 t o work i n t h e f i e l d t h a t we were working w i t h - - i n n e p h r i t i s , f o r example, a f t e r we g o t i n t o t h a t . And I would s t a r t him on a problem i n connection with that. I f h e g o t a n i d e a by h i m s e l f , why, t h a t was ok, h e c o u l d work on i t by h i m s e l f . O r i f two o f them would g e t a n idea t o g e t h e r and wanted t o team up, why t h a t was ok. O r sometimes they would team up w i t h p e o p l e o v e r i n what was c a l l e d t h e " l a b o r a t o r y p a r t " of t h e I n s t i t u t e t h a t was s e p a r a t e from t h e H o s p i t a l . There w a s n ' t any r u l e , and you might s a y t h e r e w a s no o r g a n i z a t i o n ! We j u s t d i d work t h e b e s t way t h a t seemed d e s i r a b l e under t h e c o n d i t i o n s . D r . 0.: I know D r . H a s t i n g s and I s p e n t a f a i r amount of t i m e t a l k i n g about t h e work i n hemoglobin s t u d i e s and so on; D r . H a s t i n g s was t h e r e and D r . H e i d e l b e r g e r w a s involved i n making hemoglobin f o r your s t u d i e s . D r . V.: Yes, t h e blood g a s work a l l developed o u t of t h e d i a b e t e s . That i s , t h a t g o t u s s t a r t e d . That was t h e cause of developing t h e o l d v o l u m e t r i c GO2 p i p e t t e . Then Lundsgaard came o v e r and h e was a n i n t e r n i s t i n t e r e s ed i n c i r c u l a t o r y d i s e a s e s , and h e wanted t o s t u d y blood oxygen i n c a r d a c decompensation--you're a n M.D. a r e n ' t you? Dr. 0.: Yes s i r . Ex-surgeon, e x - p a t h o l o g i s t ! Dr. V.: He wanted t o s e e whether i n decompensation t h e oxygen c o n t e n t of t h e blood d e c r e a s e s . T h a t c o u l d happen e i t h e r from pulmonary c o n d i - t i o n s where you d o n ' t g e t good o x y g e n a t i o n o r i t c o u l d happen from retarded circulation. Lundsgaard s t a r t e d doing blood oxygens--or h e called i t "unsaturations." He'd t a k e venous blood and d i v i d e it i n t o two and p a r t of i t h e ' d s a t u r a t e w i t h a i r and t h e o t h e r p a r t he a n a l y z e d 28 a s it came. He a t f i r s t used t h e Haldane a p p a r a t u s f o r d e t e r m i n i n g t h e blood oxygen. You have blood i n a b o t t l e t h a t ' s connected w i t h a l i t t l e manometer and p u t f e r r i c y a n i d e i n . A s t h e oxygen comes o u t of s o l u t i o n t h e manometer goes up. From t h a t you j u d g e how much oxygen t h e r e i s i n t h e blood. It t a k e s f i f t e e n m i n u t e s o r s o b e f o r e i t comes t o t h e top. Well, Lundsgaard k e p t on s h a k i n g t h e b o t t l e a f t e r t h a t , and he found t h a t t h e p r e s s u r e would s t a r t t o d e c r e a s e . It was obvious t h a t some o f t h e oxygen w a s b e i n g used up, and s o he was v e r y d i s t r u s t - f u l of t h e method. It t u r n s o u t , l a t e r when S t a d i e t r i e d i t o u t - - t e s t e d i t o u t - - i n comparison w i t h t h e manometric method t h a t , t h e H a l - dane method w a s a b o u t t e n p e r c e n t low b e c a u s e t h e r e were some r e d u c i n g s u b s t a n c e s , p r o b a b l y l i p i d s , t h a t used h i s oxygen up i n t h e a l k a l i n e s o l u t i o n t h a t w a s used. And t h a t is why a f t e r i t r e a c h e d a peak i t would s t a r t coming down, b u t i f you t o o k i t up t o t h e peak, and stopped then you had a b o u t 90 p e r c e n t of t h e t r u e v a l u e . But Lundsgaard d i d n ' t l i k e i t , and I s a i d , "Well, I'm s u r e you c a n do i t w i t h t h i s C02 p i p e t t e and g e t t h e answer q u i c k b e f o r e t h e r e i s t i m e f o r t h i s consumption of oxygen t o amount t o a n y t h i n g . " I was v e r y busy a t t h e t i m e , b u t I s a i d , "1'11 f i n d time t o work i t o u t p r e t t y soon." Every morning a f t e r t h a t h e ' d come t o my door and s a y , "Van, have you g o t t h a t oxygen method y e t ? " (Laughter) So I r e a l l y had t o q u i t e v e r y t h i n g e l s e I was d o i n g and work o u t t h e oxygen method. Then he w a s v e r y happy. It worked. But t h a t ' s t h e way we g o t s t a r t e d o n oxygen. The v a r i o u s f i e l d s t h a t went ahead i n my l a b o r a t o r y s t a r t e d some o n t h e o r i g i n a l impetus from one man, some from a n o t h e r . 29 D r . 0.: A l l based g e n e r a l l y on a c l i n i c a l problem t h a t h e b r i n g s t o the lab. Dr. v.: Yes, o r t h e y might go i n t o what you might c a l l b a s i c problems from t h e c l i n i c a l problem. Lundsgaard w a s a g r e a t chap. After he'd been t h e r e a l i t t l e w h i l e , h e went o u t f o r a n e v e n i n g w i t h some of t h e o t h e r young d o c t o r s and h e saw a handsome woman on t h e f l o o r of t h e h o t e l where t h e y were having c o c k t a i l s , d a n c i n g , and h e t h o u g h t h e ' d l i k e t o dance w i t h h e r and he j u s t went o u t and t i p p e d h e r p a r t n e r on the s h o u l d e r and danced o f f w i t h h e r ! (Laughter) I g o t t o d i s c u s s i n g w i t h him some problem--I've f o r g o t t e n what i t was-- b u t we had somewhat d i f f e r e n t views o n i t , and i t happened t h a t a t t h r e e o ' c l o c k i n t h e a f t e r n o o n I had a n appointment t o s e e F l e x n e r a b o u t something. I s a i d , '%Jell Chren, w e ' l l have t o f i n i s h t h i s up l a t e r , I ' v e g o t t o go o v e r and s e e F l e x n e r . " H e s a i d , "No, w e ' r e going t o f i n - i s h i t up now. You t a k e t h e t e l e p h o n e and you t e l l F l e x n e r y o u ' l l s e e him later!'' And so I d i d t h a t : D r . 0.: I g a t h e r from s p e a k i n g w i t h D r , H a s t i n g s t h a t w i t h i n t h e Rocke- f e l l e r H o s p i t a l t h e r e was r e a l l y a v e r y much open-door p o l i c y w i t h exchange of i d e a s and so on amongst t h e v a r i o u s l a b s , b u t t h a t t h i s w a s n ' t always t h e c a s e i n t h e R o c k e f e l l e r I n s t i t u t e p r o p e r . D r . V.: Well, t h e I n s t i t u t e w a s o r g a n i z e d , f o r t h e most p a r t , around s e n i o r men. They were c a l l e d members i n s t e a d of p r o f e s s o r s , and i t was a b i t on t h e o r g a n i z a t i o n of European u n i v e r s i t i e s where e a c h p r o f e s s o r 30 is p r e t t y much d i c t a t o r i n h i s own department. The H o s p i t a l was l e s s t h a t way. When i t s t a r t e d , t h e D i r e c t o r , D r . Cole--1 t h i n k h e w a s 35-- and everybody e l s e w a s around 30. T h e r e were no s e n i o r o l d e r men l i k e Dr. M e l t z e r was. D r . M e l t z e r w a s a German and n a t u r a l l y t h i n g s would go i n h i s department a s a German p r o f e s s o r would o r g a n i z e t h i n g s . Things were more, you might s a y , " f r e e and e a s y " i n the Hospital. You could work on p r a c t i c a l l y a n y t h i n g you wanted t o . I f you wanted t o s t a r t a new d i s e a s e n a t u r a l l y you would s e t t l e t h a t w i t h D r . Cole. But what you would do w i t h i t , what problems you t a k e up w i t h i t , Cole would never attempt t o d i c t a t e . When i t came t o a p p o i n t m e n t s , i f a man wanted t o come t o work w i t h me I ' d s e e D r . Cole a b o u t i t and i f p o s s i b l e have him i n t e r v i e w D r . Cole, t h e n D r . F l e x n e r would approve i t and i t would be approved by t h e Board of S c i e n t i f i c D i r e c t o r s . I never recommended a man t h a t w a s n ' t a p p o i n t e d . It w a s as i n f o r m a l a s t h a t . D r . 0.: Could you g i v e m e your i m p r e s s i o n s of D r . Cole? He c e r t a i n l y is a n i m p o r t a n t f i g u r e i n contemporary medicine. D r . V.: Yes. He w a s a v e r y f i n e man, b o t h p e r s o n a l l y and s c i e n t i f i c a l l y . I ' v e h e a r d i t s a i d t h a t h e w a s c o n s i d e r e d t h e b r i g h t e s t man t h a t e v e r g r a d u a t e d from Hopkins a t t h e t i m e t h a t he g r a d u a t e d . But he came t o t h e I n s t i t u t e w i t h t h e i d e a t h a t the l a b o r a t o r y and the c l i n i c would work a s one organism. As t h e H o s p i t a l s t a r t e d o u t , most of t h e young men t h e r e t h a t were working on p a t i e n t s d i d t h e i r own l a b o r a t o r y work. E v e n t u a l l y , l a b o r a t o r y p r o c e d u r e s g o t so numerous and c o m p l i c a t e d t h a t t h a t was no l o n g e r p r a c t i c a l , b u t t h a t was t h e idea--Dr. Cole's idea-- 31 t h a t l a b o r a t o r y and c l i n i c should n o t be s e p a r a t e d . And t h e y p r e t t y much c o n t i n u e d t h a t way, t h a t i s , I always had a c o u p l e o f c h e m i s t s working w i t h m e t h a t were Ph.D. c h e m i s t s , b u t I a l s o had u s u a l l y f o u r o r f i v e M.D.s working w i t h me, b u t t h e y a l s o worked i n t h e l a b o r a t o r y . A l l of them. D r . 0.: YOU mean a l s o i n t h e c l i n i c , w h i l e t h e y w e r e working----- D r . V.: Yes, t h e y had p a t i e n t s , t h e y were i n c h a r g e o f p a t i e n t s , b u t t h e i d e a was t o have so few p a t i e n t s p e r d o c t o r and t h a t t h e d o c t o r c o u l d a l s o do l a b o r a t o r y work. And t h e i d e a w a s , f u r t h e r m o r e , t o have a few p a t i e n t s t h a t s h o u l d be s t u d i e d as c o m p l e t e l y as p o s s i b l e r a t h e r t h a n have a g r e a t many p a t i e n t s from whom you c o l l e c t e d j u s t what you might c a l l routine data. And i n c i d e n t a l l y , t h a t ' s t h e p l a n on which the Brook- haven Medical Department s t a r t e d and c o n t i n u e s . D r . 0.: How many beds do you have h e r e ? D r . V.: We have 48 b e d s , and a l l t h e p a t i e n t s - - t h e same a s t h e y were i n t h e R o c k e f e l l e r - - a r e p a t i e n t s who pay n o t h i n g and c a n , f o r t h a t rea- son, s t a y a s l o n g as i t i s e s s e n t i a l t o s t u d y them. They a r e u s u a l l y happy t o s t a y . W e d e l i b e r a t e l y s t a r t e d t h e Brookhaven Medical Department on D r . C o l e ' s p r i n c i p l e s . It would be f a i r t o c a l l i t "The Cole Medical Department. " D r . 0.: I n t h e e a r l y days o f t h e R o c k e f e l l e r I n s t i t u t e , what w a s t h e r e a c t i o n amongst t h e academic c o m u n i t y , i n New York, i n l o c a l m e d i c a l c e n t e r s , m e d i c a l i n s t i t u t i o n s , p l a c e s l i k e Columbia. I gather that there 32 were people who worked i n your department who were g e t t i n g advanced degrees a t Columbia w h i l e t h e y worked a t t h e I n s t i t u t e . Dr. V.: Yes, I had t h r e e c h e m i s t s who had b a c h e l o r ' s d e g r e e s when t h e y came t o work w i t h me and i t was a r r a n g e d t h a t t h e y g o t a Ph.D. from Columbia w h i l e t h e y c o n t i n u e d t h e i r work i n my department. D r . 0.: I was j u s t wondering w h e t h e r o r n o t t h e r e w a s any s o r t of ''sour g r a p e s " f e e l i n g t o w a r d t h e I n s t i t u t e from t h e s u r r o u n d i n g academic community. Dr. V.: I t h i n k t h e r e w a s v e r y l i t t l e o f t h a t and p e r h a p s f o r t h e r e a - son t h a t we r e a l l y d i d n ' t compete. We had so few p a t i e n t s . We've r e a l l y h a r d l y competed w i t h t h e o t h e r s c h o o l s . P e r s o n a l l y , I always had c o r d i a l r e l a t i o n s w i t h my c o l l e a g u e s i n t h e o t h e r m e d i c a l s c h o o l s , i n t h e medical s c h o o l s i n New York and e l s e w h e r e f o r t h a t m a t t e r . Dr. 0.: I ' v e s e e n it somewhere, I c a n ' t remember where, b u t somewhere the s t a t e m e n t t h a t t h e " u n i v e r s i t y concept" of t h e R o c k e f e l l e r I n s t i t u t e s t a r t e d when D e t l e v Bronk w a s t h e D i r e c t o r . This r e a l l y seems t o be a n i n j u s t i c e because o b v i o u s l y , t a k i n g your department a s a n example, you were doing one d e v i l of a l o t of t e a c h i n g l o n g b e f o r e . D r . V.: The R o c k e f e l l e r I n s t i t u t e , b e f o r e i t became a u n i v e r s i t y , w a s really a postdoctoral university. Most of t h e p e o p l e t h a t worked there up t o t h a t time a l r e a d y had t h e i r d o c t o r ' s d e g r e e s . Not always. As I s a y , t h e r e were t h r e e men t h a t s t a r t e d a s t e c h n i c i a n s w i t h b a c h e l o r ' s degrees a n d used t h e i r work a t t h e R o c k e f e l l e r as t h e s e s . But f o r t h e 33 most p a r t , t h e young men t h a t came t o work t h e r e were t h e same a s I was, they a l r e a d y had t h e i r M.D.s o r t h e i r Ph.D.s, and t h e y would work t h e r e u s u a l l y not l e s s t h a n two y e a r s - - t w o t o f i v e , seven--and t h e n go o u t t o f a c u l t y p o s i t i o n s i n u n i v e r s i t i e s o r t o r e s e a r c h o r h e a d s of r e s e a r c h laboratories. It was, I t h i n k , d e f i n i t e l y a n e d u c a t i o n a l i n s t i t u t i o n . Bronk changed i t t o a g r a d u a t e s c h o o l t h a t s p e c i a l i z e d on p r e d o c t o r a l students. D r . 0.: Now r e a l l y t h e change i n name, I d o n ' t t h i n k , h a s changed t h e concept o f what t h e y ' v e been d o i n g f o r some w h i l e . I t ' s j u s t t h a t they e l e c t e d t o t a k e t h e name U n i v e r s i t y a s opposed t o I n s t i t u t e . D r . V.: W e l l , t h e c h a r a c t e r of t h e I n s t i t u t e h a s changed i n t h a t t h e medical s i d e of i t i s much l e s s emphasized t h a n i t was. I think t h a t was Bronk's i d e a . I r e g r e t t e d it. I think the school's a f i n e thing as i t i s now, b u t I was s o r r y t o s e e t h e m e d i c a l s i d e of it g r a d u a l l y d e - emphasized. S e n i o r m e d i c a l men have l e f t and I d o n ' t t h i n k t h e y ' v e appointed o t h e r s i n medicine. And t h e H o s p i t a l w a s a d e f i n i t e s u b - u n i t o f t h e I n s t i t u t e w i t h a v e r y h i g h morale under D r . Cole and under Rivers a f t e r Cole r e t i r e d , w i t h a d i r e c t o r as Cole and R i v e r s were. Now t h e r e is no h o s p i t a l d i r e c t o r , t h e r e ' s a Chief P h y s i c i a n . But t h e s p e c i a l c h a r a c t e r of t h e H o s p i t a l i s n o t changed. D r . 0.: Yes, i t c e r t a i n l y sounds l i k e a f a i r amount of deemphasis of medicine. D r . V.: Yes, and t h e I n s t i t u t e h a s a P r o f e s s o r of P h i l o s o p h y , P r o f e s s o r of Mathematics . 34 Dr. 0.: Have you s e e n t h i s o r a l h i s t o r y memoir o f D r . R i v e r s t h a t w a s done by S a u l Benison? D r . V.: No, I h a v e n ' t . D r . 0.: I t ' s q u i t e i n t e r e s t i n g reading. D r . V.: I haven't. I must g e t i t . Do you know who p u b l i s h e d i t ? D r . 0.: Yes, M.I.T. Press. It came o u t i n l a t e ' 6 7 I b e l i e v e . D r . V.: The a u t h o r w a s S a u l Benison? D r . 0.: Yes, B-e-n-i-s-o-n. I know S a u l q u i t e w e l l , H e ' s been v e r y interested i n the Rockefeller I n s t i t u t e . D r . V.: T h a t ' s t h e l i f e of R i v e r s ? D r . 0.: Yes. I t ' s c a l l e d Tom R i v e r s : R e f l e c t i o n s on L i f e i n S c i e n c e and Medicine, an Oral H i s t o r y Memoir. It's very interesting t o hear the r e a c t i o n of t h o s e who knew D r . R i v e r s who have r e a d i t . D r . V.: The M.I.T. Press. Yes, I ' v e h e a r d a b o u t t h a t and I must g e t i t . D r . 0.: I t h i n k some f e e l t h a t t h e r e ' s c e r t a i n l y much o f Tom R i v e r s t h e r e because i t , a g a i n , i s a n o r a l h i s t o r y memoir which h a s been e d i t e d r a t h e r e x t e n s i v e l y , b u t f o r t h o s e l i k e myself who o n l y knew t h e man by r e p u t a t i o n and by secondhand i n f o r m a t i o n , i t seems t o c a p t u r e a l o t of the f l a v o r of what he must have been l i k e . But many who a p p a r e n t l y knew him f e l t t h a t p e r h a p s he s h o u l d have been i n t e r v i e w e d a few y e a r s s o o n e r 35 than h e was. That i t w a s n ' t t h e Tom R i v e r s t h e y remembered. He w a s a l i t t l e e m b i t t e r e d h e r e and t h e r e . But i t ' s q u i t e a document r e a l l y . I t ' s a n e x c e l l e n t panorama of t h i s p e r i o d a t t h e R o c k e f e l l e r Dr. V.: I n e v e r t a l k e d w i t h him a b o u t it b u t I c a n imagine t h a t he r e g r e t t e d t h e f a c t t h a t he had no s u c c e s s o r a s D i r e c t o r o f t h e H o s p i t a l . The H o s p i t a l i s s t i l l running. We s t i l l have p a t i e n t s . But i t w a s n ' t long a f t e r Bronk came b e f o r e he changed t h e t i t l e of t h e R o c k e f e l l e r I n s t i t u t e f o r M e d i c a l Research, h e dropped o f f t h e "Medical Research." Dr. 0.: Oh, I had f o r g o t t e n t h a t . Very i n t e r e s t i n g . D r . V.: And t h e n a f t e r t h a t it became t h e R o c k e f e l l e r U n i v e r s i t y . A t t h e t i m e , I f e l t t h a t we had enough u n i v e r s i t i e s , b u t t h e r e w a s o n l y one R o c k e f e l l e r I n s t i t u t e a c t i n g a s a p o s t d o c t o r a l u n i v e r s i t y . I would have p r e f e r r e d t o keep i t t h a t way. A s a m a t t e r of f a c t , t h e N a t i o n a l I n s t i t u t e s of H e a l t h was modeled on t h e R o c k e f e l l e r . So t h e world no l o n g e r , you might s a y , needed t h i s a s a n e x a m p l e - - t h a t i s , t h e o l d Rockefeller. A s a matter of f a c t , when t h e y were p l a n n i n g t h e N a t i o n a l I n s t i t u t e s of H e a l t h , t h e y came up and examined t h e I n s t i t u t e i n o r d e r t o u s e t h e p h y s i c a l p l a n o n which t h e I n s t i t u t e w a s working. D r . 0.: Plus, I ' m sure, the close relationship with the Hospital t o the I n s t i t u t e and t h e H o s p i t a l , i n a s e n s e , t o t h e p e r s o n n e l h a v i n g p a t i e n t r e s p o n s i b i l i t i e s as w e l l a s l a b o r a t o r y . D r . V.: The N a t i o n a l I n s t i t u t e s of H e a l t h i s a d a r n good i n s t i t u t i o n though. 36 Dr. 0.: Yes. I s p e n t f o u r y e a r s t h e r e , no I beg y o u r p a r d o n , s i x y e a r s - - two y e a r s i n t h e S u r g i c a l Branch of t h e Cancer I n s t i t u t e , and t h e n a f t e r two y e a r s away, I came b a c k and went t h r o u g h the Pathology program t h e r e . Two y e a r s a t P a t h Anatomy and two y e a r s a t C l i n i c a l Pathology. D r . V.: There a r e a l o t o f v e r y f i n e men t h e r e . A n f i n s e n went back t o Harvard and o n l y s t a y e d t h e r e a y e a r and r e t u r n e d t o t h e N a t i o n a l Institutes Dr. 0.: I didn't realize that. I d i d n ' t r e a l i z e h e ' s been o f f f o r a year. D r . V.: yes. He took a C h a i r a t Harvard, b u t he o n l y s t a y e d t h e r e a year. I never asked him why h e went back. He's a g r e a t chap. [Break f o r l u n c h ] D r . 0.: I f you c o u l d , f o r t h e s a k e of t h e r e c o r d , t e l l me a b o u t your e x p e r i e n c e s a t t h e Peking Union Medical C o l l e g e . D r . V.: Yes. I w a s a p p o i n t e d V i s i t i n g P r o f e s s o r t o go o u t t h e r e i n t h e f a l l of 1922. That was t h e time when H a s t i n g s and I had g o t t e n s t a r t e d on o u r s t u d i e s of g a s and e l e c t r o l y t e e q u i l i b r i a i n t h e blood. We had determined a t t h a t time t h a t t h e hemoglobin of t h e c e l l s bound more base--or balanced more c a t i o n , whichever way you want t o p u t i t - - t h a n t h e r e had been any i d e a o f b e f o r e . I n blood w i t h a r a t h e r h i g h pH, f o r example 7.6, a b o u t 50 p e r c e n t of t h e c a t i o n i n t h e c e l l s was b a l a n c e d by hemoglobin a c t i n g as a n i o n . W e l l , i t had been known f o r a l o n g time t h a t t h e c o n c e n t r a t i o n s of c h l o r i d e and b i c a r b o n a t e i n t h e c e l l s a r e 37 much l e s s t h a n t h e y a r e i n t h e serum, and we had a hunch t h a t t h e hemoglobin, a c t i n g as a n e l e c t r o l y t e a n i o n , w a s r e s p o n s i b l e f o r i t . On t h e way t o China, I had a c o u p l e of weeks on t h e b o a t t o f i g u r e on i t and g o t t h e i d e a t h a t we had a Donnan e q u i l i b r i u m which you g e t when you have two s o l u t i o n s s e p a r a t e d by a membrane and p a r t of t h e e l e c t r o l y t e i n one o f t h e s o l u t i o n s i s n o n d i f f u s i b l e . So I planned a s e t of e x p e r i m e n t s t o do w i t h d e t e r m i n a t i o n s o f c h l o r i d e and C 0 2 , t o t a l b a s e , and pH i n c e l l s and serum t o t e s t t h i s o u t . W e l l , a t Peking, a t t h a t t i m e , t h e P r o f e s s o r of Medicine w a s McLean who had been w i t h u s and w i t h L. J. Henderson when we g o t s t a r t e d on t h e s e problems. The P r o f e s s o r of Chemistry t h e r e was H s i e n Wu, of t h e Folin-Wu methods. A s soon as I g o t t o Peking, I l a i d t h i s p l a n o u t b e f o r e Wu and McLean. McLean had a r i d i n g pony t h a t was v e r y handy t o g e t p l e n t y of b l o o d from. So we s t a r t e d t h e n e x t day t o p u t h i s blood under d i f f e r e n t C 0 2 t e n s i o n s and s e e how t h e t h e o r y worked o u t . There were a l o t o f a n a l - y s e s t o do w i t h e a c h experiment. We r a n h i g h and low and m e d i u m C 0 2 t e n s i o n s and o b s e r v e d t h e e f f e c t s on t h e s h i f t of c h l o r i d e back and f o r t h and a l s o the s h i f t s of w a t e r i n and o u t of t h e c e l l s . One o f t h e t h i n g s we found o u t immediately was t h a t i n o r d e r t o g e t meaningful c o n c e n t r a t i o n r e s u l t s , t h e y had t o b e e x p r e s s e d i n terms of amount of c h l o r i d e o r b i c a r b o n a t e o r whatever i t w a s p e r k i l o of w a t e r and not p e r u n i t volume--not per liter. Because i n t h e c e l l s , t h e hemoglobin t a k e s up s u c h a l a r g e volume, t h a t i s , t h e c e l l s have o n l y something l i k e 80 p e r c e n t of w a t e r . I n w e i g h t , t h e c e l l s have g o t a b o u t 34 p e r - c e n t of hemoglobin and something o v e r 60 p e r c e n t of w a t e r , and t h e hemoglobin, of c o u r s e , t a k e s up a good d e a l of volume. But a s soon as 38 we p u t o u r r e s u l t s on a b a s i s of amount of c h l o r i d e , b i c a r b o n a t e and so f o r t h p e r k i l o of w a t e r , t h e n t h e c r y s t a l l i z i n g meant something. I t h i n k t h a t when t h a t s y s t e m of e x p r e s s i n g c o n c e n t r a t i o n s was i n t r o - duced was when we w r o t e t h a t paper. Well, I w a s t h e r e f o u r months and we r a n t h r e e b i g e x p e r i m e n t s . Wu r e a l l y handled it. He had t h r e e Chinese t e c h n i c i a n s , and t h e y g o t t h e glassware and e v e r y t h i n g r e a d y f o r e v e r y e x p e r i m e n t . Wu r e a l l y o r g a n - ized t h e work. He d i d i t so b e a u t i f u l l y t h a t we d i d n ' t l o s e a s i n g l e experiment. U s u a l l y you work f o r a b o u t h a l f a y e a r b e f o r e you f i n d c o n d i t i o n s t h a t g o , b u t we d i d n ' t l o s e a n y t h i n g . And t h a t work r e s u l t e d i n No. 5 i n t h e e q u i l i b r i a s e r i e s . [Going t o t h e b o o k s h e l f ] I have a copy of i t bound. T h e r e ' s one of t h e d i a g r a m s - - t h a t ' s the apparatus t h a t we developed j u s t f o r t h e d e t e r m i n a t i o n . D r . 0.: T h i s c e r t a i n l y is one of t h e c l a s s i c a l p a p e r s i n t h e f i e l d of e l e c t r o l y t e and w a t e r balance. D r . V.: I t h i n k so. A d d i t i o n a l f a c t o r s have been added t o t h e p i c t u r e , but t h i s work developed i t s main f a c t o r s . The c l e a r a r e a s h e r e r e p r e - s e n t o s m o t i c a l l y a c t i v e c o n c e n t r a t i o n s , and t h e shaded a r e a r e p r e s e n t s hemoglobin a c t i n g as a n a n i o n , which i s not o s m o t i c a l l y a c t i v e . Well, the c l e a r areas osmolar c o n c e n t r a t i o n s i n c e l l s e q u a l t h e c l e a r a r e a s f o r serum. So, inasmuch a s hemoglobin a n i o n i s p r a c t i c a l l y i n a c t i v e , o s m o t i c a l l y , t h e r e h a s t o be a good d e a l more c a t i o n ( p o t a s s i u m , m o s t l y ) , c o n s e q u e n t l y l e s s c h l o r i d e and l e s s b i c a r b o n a t e i n c e l l s t h a n i n plasma. Which e x p l a i n s why t h e r e ' s o n l y a b o u t 60 p e r c e n t t h e c o n c e n t r a t i o n of 39 b i c a r b o n a t e and c h l o r i d e i n t h e r e d c e l l s t h a t t h e r e i s i n plasma. This imaginary e x p e r i m e n t s t a r t s w i t h a low C 0 2 and pH o f 8. Then we run i n C 0 2 u n t i l t h e pH goes down t o a b o u t 6.7 where hemoglobin i s a t i t s i s o e l e c t r i c p o i n t and d o e s n ' t b i n d a n y t h i n g , t h a t i s , i t a c t s a s a nonelectrolyte. So, t h i s area h e r e - - i f t h i s is a l l o s m o t i c a l l y a c - t i v e , you have a g r e a t d e a l h i g h e r o s m o t i c c o n c e n t r a t i o n t h a n you h a v e here. And a l s o , the r a t i o o f t h e c h l o r i d e t o b i c a r b o n a t e i n c e l l s i s much lower t h a n i n plasma----the hemoglobin a n i o n i n t h e c e l l s h a s been r e p l a c e d by b i c a r b o n a t e . The r a t i o of b i c a r b o n a t e i n c e l l s t o b i c a r - bonate i n serum is much g r e a t e r t h a n t h e c h l o r i d e . Now, a c c o r d i n g t o t h e Donnan e q u i l i b r i u m t h o s e a n i o n s must have the same r a t i o . So, c h l o r i d e s h i f t s t o t h e c e l l s and b i c a r b o n a t e s h i f t s from t h e c e l l s o u t t o t h e plasma u n t i l you g e t t h e r a t i o s e q u a l i z e d . The p r o c e s s e x p l a i n s why, i f you r u n C 0 2 i n t o t h e b l o o d , t h e b i c a r b o n a t e i n t h e plasma increases. A f t e r t h e s e e v e n t s you have a g r e a t e r osmolar c o n c e n t r a t i o n i n t h e c e l l s t h a n i n plasma t h a n you have h e r e so t h a t i n t h e l a s t d i a - gram you have water p a s s i n g from t h e plasma i n t o t h e c e l l s , and t h e c e l l s s w e l l u n t i l you g e t e q u a l o s m o t i c c o n c e n t r a t i o n s . T h a t e x p a i n s why t h e c e l l s s w e l l up when you r u n C 0 2 i n t h e blood. W e l l , t h a t ' s a "nut- s h e l l " o f what we worked o u t i n Peking. D r . 0.: I know D r . H a s t i n g s h a s r e f e r r e d t o t h i s p a r t i c u l a r b i t o f work because he w a s s o s t r u c k by t h e f a c t t h a t you had s e n t t h i s l e t t e r which e s s e n t i a l l y had t h e q u e s t i o n answered; i t w a s j u s t a matter of f i l l i n g i n t h e v a l u e s , as i t were, when you s t a r t e d working i n t h e laboratory. He s t i l l h a s t h a t l e t t e r , by the way, which you p r o b a b l y realize! 40 D r . V.: Yes, I know. He r e a d i t a t a seminar we had i n Ann Arbor a few y e a r s ago. No, i t w a s a c e l e b r a t i o n t h e y had h e r e on my 8 0 t h b i r t h d a y and H a s t i n g s spoke of i t . He r e a d a p a r t of t h a t l e t t e r . I d i d n ' t know he s t i l l had i t ! D r . 0.: Oh y e s . I n f a c t t h e r e i s q u i t e a f i l e of Van Slyke c o r r e s p o n d - ence t h e r e D r . V.: W e l l , we worked t h a t o u t and I had a v e r y good time i n Peking, too. I t o o k a Chinese l e s s o n e v e r y day a f t e r l u n c h and t h e n my w i f e arranged a l i t t l e t o u r around some of t h e p a r t s o f Peking. A s i d e from t h a t , t h e r e was n o t h i n g t o do e x c e p t t h e s e e x p e r i m e n t s , none of t h e t h i n g s t h a t w a s t e your time when y o u ' r e a t home. So we f i n i s h e d t h a t work i n t h r e e o r f o u r months. There were a l o t of d e t a i l s t o work o u t ; t h i n g s t o do more a c c u r a t e l y - - - - - - D r . 0.: Yes, when you r e t u r n e d t o t h e R o c k e f e l l e r . D r . V.: - - - - -when we g o t back. D r . 0.: You were o n l y a t PUMC o n one o c c a s i o n ? D r . V.: I w a s o n l y t h e r e o n c e , yes. I made f r i e n d s t h a t I s t i l l h a v e , and involvements w i t h Chinese f r i e n d s which I s t i l l have and which g o t me i n t o a l o t of work d u r i n g t h e war because when t h e Japanese a t t a c k e d China i n 1937, t h r e e Chinese--two of whom were p h y s i c i a n s i n New York-- organized t h e American Bureau f o r Medical A i d t o China t o h e l p t h e Chinese o u t and t h e y g o t me t o j o i n them. I c o u l d n ' t r e f u s e because I was so s y m p a t h e t i c w i t h t h e Chinese when t h e y were a t t a c k e d by Japan. 42 [Side I , Reel 21 May 2 7 , 1969. Dr. 0.: C e r t a i n l y one of t h e names t h a t t o anyone who h a s been exposed t o b i o c h e m i s t r y and c l i n i c a l b i o c h e m i s t r y i n p a r t i c u l a r , med- i c a l s t u d e n t s and o t h e r w i s e , i s Lawrence J. Henderson who i s a v e r y , I g a t h e r , c l o s e f r i e n d of y o u r s . I wonder i f you wou d n ' t mind s a y i n g a few words a b o u t him. I might s a y , o b v i o u s l y , a s we 1 a s f o l l o w i n g along y o u r c a r e e r , i t ' s always n i c e t o g e t some f l e s h o n t o some of t h e s e names which t o so many of u s , who a r e n o t d e e p l y i n t h i s f i e l d , t h e y a r e names we s e e from t h e minute you s t a r t and y e t you d o n ' t r e a l l y have a p i c t u r e of t h e s e people. I t h i n k i t ' s v e r y i n t e r e s t i n g and i m p o r t a n t t h a t we have some s o r t of a r e c o r d of what t h e y ' r e l i k e . D r . V.: Yes. Henderson w a s a unique c h a r a c t e r . He was n o t much of a l a b o r a t o r y worker h i m s e l f , b u t he was a g r e a t t h i n k e r , a g e n e r a l i z e r . There i s o c c a s i o n a l l y a s c i e n t i s t who comes a l o n g who i s tremendously v a l u a b l e i n p u l l i n g t h i n g s t o g e t h e r t h a t have been uncovered by o t h e r men and i s s t i m u l a t i n g . U s u a l l y , I t h i n k t h e g e n e r a l i z e r who d o e s n ' t work h i m s e l f i s not l i k e l y t o be one whose g e n e r a l i z a t i o n s a r e w o r t h a g r e a t d e a l because h e d o e s n ' t have t h e s e n s e o f ----- D r . 0.: Perspective, possibly? Dr. v.: ----- p e r s p e c t i v e o f r e l a t i v e v a l u e s , of p r o b a b l e e x p l a n a t i o n s a g a i n s t t h e improbable ones. But Henderson d i d have t h a t s e n s e . He d i d do some work h i m s e l f i n h i s e a r l y days. I f i r s t came i n c o n t a c t w i t h h i s work when C u l l e n and I r a n up a g a i n s t the problem of a c i d o s i s i n diabetes. We r e a d up l i t e r a t u r e t h a t might be h e l p f u l , and t h e p a p e r 43 t h a t r e a l l y g o t u s s t e e r e d o n o u r work was a p a p e r by Henderson on t h e a c i d - b a s e b a l a n c e of t h e b l o o d , t h a t w a s p u b l i s h e d i n German, i n which he brought o u t t h e Henderson e q u a t i o n and p o i n t e d t h e importance o f b i c a r b o n a t e a s t h e a l k a l i r e s e r v e o f t h e blood. Then I g o t p e r s o n a l l y a c q u a i n t e d w i t h Henderson; I had m e t him b e f o r e t h a t b u t I g o t b e t t e r a c q u a i n t e d w i t h him. McLean had worked w i t h Henderson f o r awhile. McLean, when Henderson w a s working on t h i s problem of what i t i s t h a t makes t h e d i f f e r e n c e between c e l l and serum e l e c t r o l y t e s ; Henderson c o l l e c t e d t h e d a t a b u t he d i d n ' t have t h e e x p l a n a t i o n t h a t w e g o t when we found t h a t hemoglobin bound so much a l k a l i . He d i d n ' t know what i t was t h a t caused t h e d i f f e r e n c e , b u t h e c o l l e c t e d t h e d a t a and he pub- l i s h e d a c o m p l i c a t e d nomogram t h a t showed how much c h l o r i d e s h i f t s i f you have a s h i f t i n b i c a r b o n a t e o r v i c e v e r s a , and haw much a n oxygen s h i f t c a u s e s a s h i f t i n t h e o t h e r t h i n g s , and s o f o r t h . It was t h e d i s c o v e r y o f t h e amounts of a l k a l i t h a t a r e bound by reduced hemoglobin and o x i d i z e d hemoglobin t h a t H a s t i n g s and I worked o u t t h a t gave t h e key t o why t h e s e d i f f e r e n c e s a r e . But Henderson l a i d o u t t h e problem i n showing t h a t t h e d i f f e r e n c e s were t h e r e and a p p r o x i m a t e l y what t h e y were. There was n o t a c c u r a t e d a t a a v a i l a b l e u n t i l we t o o k the problem up and developed methods p a r t i c u l a r l y t o g e t t h e d a t a . But Henderson saw t h a t t h e problem w a s t h e r e and o u t l i n e d i t c l e a r l y . He was r e a l l y a g r e a t man. I n s t e a d o f b e i n g m i f f e d because we g o t t h e f i n a l s o l u t i o n , he was d e l i g h t e d ! T h e r e were q u i t e a number o f men t h a t worked w i t h him, a l l of whom developed i n t o l e a d e r s . There w a s W. W. Palmer, who became P r o f e s s o r o f Medicine a t Columbia. Palmer came and worked w i t h me f o r a y e a r o r two a f t e r he l e f t Henderson, t h e n he became P r o f e s s o r 44 Medicine a t Columbia; and R e d f i e l d who s t a y e d i n p h y s i o l o g y a t Harvard; Binger, who came and worked a t t h e R o c k e f e l l e r , e v e n t u a l l y went i n t o psycho logy. D r . 0.: Oh y e s , I remember D r . H a s t i n g s mentioned h e was t h e w e l l - dressed chap. D r . V.: Yes, h e w a s always i n good shape. Anytime you were w i t h Hen- derson you f e l t rewarded. H e had a camp up i n n o r t h Vermont n e a r t h e Canadian b o r d e r and one t i m e t h e r e were f i v e o f u s went up t h e r e and s p e n t s e v e r a l d a y s w i t h h i m j u s t t a l k i n g a s i d e - - P a l m e r and B i n g e r , and A r l i e Bock, who d i d q u i t e a good d e a l o f t h e work. Some of t h e work t h a t we d i d on h o r s e blood w a s r e p e a t e d i n Henderson's l a b o r a t o r y on human b l o o d , and A r l i e Bock and D. B. D i l l d i d a good d e a l of t h e work. D i l l was t h e man who l e d t h e e x p e d i t i o n t o t h e Andes t h a t H a s t i n g s was due t o go on, when H a s t i n g s w a s d i v e r t e d t o become a P r o f e s s o r a t Harvard D r . 0.: Yes, t h a t ' s where t h e name is f a m i l i a r . D r . V.: Henderson had bought t h i s small farm up i n n o r t h Vermont and b u i l t a v e r y d e l i g h t f u l c a b i n on i t , o r v i l l a , whichever you would c a l l it. It was b e a u t i f u l l y a r r a n g e d . He loaned i t t o me f o r two summers when he was i n Europe, s o I went t h e r e w i t h my f a m i l y . There w a s a b a r n on i t and he g o t t h e i d e a o f f i t t i n g t h e b a r n up f o r a l a b o r a t o r y , so t h a t h i s men c o u l d come up t h e r e and work i n t h e sumnertime. He f i g u r e d i t would c o s t f i v e thousand d o l l a r s . I went t o John D. R o c k e f e l l e r , Jr. and asked him i f t h e R o c k e f e l l e r Foundation c o u l d p r o v i d e t h e f i v e 45 thousand d o l l a r s , and h e s a i d , "No, P r o f e s s o r Henderson h a s g o t o t h e r f r i e n d s t h a t c a n do that!" He s a i d i f h e was s t u c k f o r f i v e m i l l i o n , he s a i d , "We'd b e g i n t o t h i n k a b o u t it:" D r . 0.: Oh my! I g u e s s i t w a s s u c h a small r e q u e s t . D r . V.: I can understand t h e Rockefeller Foundation doubtless got hundreds of small r e q u e s t s coming i n and i t would j u s t have been admin- i s t r a t i v e l y i m p o s s i b l e t o look them a l l up and d e c i d e w h e t h e r t h e y were worthwhile o r n o t . So I t h i n k what t h e y d i d m o s t l y was t o d e c i d e them- s e l v e s what t h e y would s u p p o r t r a t h e r t h a n w a i t f o r o t h e r p e o p l e t o request it. D r . 0.: C e r t a i n l y a n o t h e r name which goes a l o n g w i t h t h e t e x t b o o k , P e t e r s and Van S l y k e , I u n d e r s t a n d D r . P e t e r s - - J a c k P e t e r s , a s he was known--was a r a t h e r i n t e r e s t i n g i n d i v i d u a l . Dr. v.: He was. D r . 0.: One who s t o o d h i s ground when he t h o u g h t h e w a s i n t h e r i g h t . D r . V.: He was a g r e a t f e l ow. H i s t e c h n i q u e i n t h e l a b o r a t o r y was beautiful. He had e x t r a o r d n a r i l y good hands. He w a s v e r y good a t drawing. When he w a s i n m e d i c a l s c h o o l , McCallum was w r i t i n g h i s t e x t - book i n p a t h o l o g y and P e t e r s drew some of t h e f i g u r e s i n t h a t . D r . 0.: Oh, f o r h e a v e n ' s s a k e , I h a d n ' t r e a l i z e d t h a t . D r . V.: P e t e r s t o l d me t h a t . I n t h e P e t e r s and Van Slyke q u i t e a num- b e r of t h e drawings i n t h e Methods volume, P e t e r s made them. He w a s 46 p r e c i s e and e x a c t and i t was t h e same way i n t h e l a b o r a t o r y . He was red- headed and loved a n argument! When we s t a r t e d w r i t i n g t h e book t o g e t h e r a f t e r he asked me t o j o i n him on i t , t h e f i r s t c h a p t e r h e s e n t me I made q u i t e a l o t of a d d i t i o n s and changes i n i t and w r o t e him a l e t t e r , as I remember, e x p l a i n i n g why I t h o u g h t t h e r e should be some changes and g o t back a l e t t e r a r g u i n g why t h e y s h o u l d n ' t be made. E v e n t u a l l y , we g o t i t s t r a i g h t e n e d o u t , b u t a f t e r t h a t I merely r e v i s e d e v e r y c h a p t e r he w r o t e - - sometimes he w r o t e t h e f i r s t d r a f t and sometimes I would. I merely made my r e v i s i o n s and s e n t i t back w i t h o u t comment and t h e n i t w a s a l l r i g h t ! (Laughter) But i f I s t a r t e d t o j u s t i f y them t h a t b r o u g h t a n argument. One time t h e r e was a meeting of a F e d e r a t e d Biology S o c i e t y i n Montreal. I d i d n ' t go t o i t , b u t P e t e r s and C u l l e n d i d and t h e y s t o p p e d a t my house i n B r o n x v i l e , where I w a s l i v i n g t h e n , on t h e i r way home. They s p e n t the n i g h t w t h me. Well, i n t h e e v e n i n g as we were s i t t i n g by t h e f i r e - s i d e , P e t e r s e x p r e s s e d some view a b o u t a p h y s i o l o g i c a l p o i n t - - I ' v e for- g o t t e n what i t was--and C u l l e n s a i d , "Yes, I t h i n k y o u ' r e r i g h t , " and added some r e a s o n s f o r i t , and P e t e r s s a i d , "NO, you d o n ' t a g r e e w i t h me and t h e s e t h i n g s a r e d i f f e r e n t . You d o n ' t a g r e e w i t h what I s a i d a t all." W e l l , t h e n a n argument s t a r t e d . P e t e r s t r y i n g t o persuade Cullen t h a t C u l l e n d i d n ' t a g r e e w i t h him a n d C u l l e n t r y i n g t o p e r s u a d e P e t e r s t h a t he did a g r e e and i t came 11 o ' c l o c k and my w i f e excused h e r s e l f and went t o bed. And it came 1 2 o ' c l o c k and I s a i d , ' W e l l , w e ' l l f i n i s h t h i s i n t h e morning," and I p u t t h e f i r e out! (Laughter) D r . 0.: H e ' s q u i t e famous f o r t h a t . 47 Dr. V.: Yes, he loved a n argument. But h e was a b e a u t i f u l worker tireless: D r . 0.: He w a s n ' t Department Chief a t Yale, I d o n ' t b e l i e v e , I t h i n k D r . B l a k e - - F r a n c i s Blake--was P r o f e s s o r of Medicine when D r . P e t e r s w a s there. D r . V.: They were b o t h P r o f e s s o r s . I d o n ' t know what t h e o r g a n i z a t i o n was w i t h r e g a r d t o t h e chairmanship. P e t e r s was i n c h a r g e of m e t a b o l i c d i s e a s e s and Blake of i n f e c t i o u s d i s e a s e s . D r . 0.: Well a c t u a l l y , F r a n c i s Blake had s p e n t some t i m e a t t h e Rocke- f e l l e r , had h e n o t ? Dr. V.: Yes. D r . 0.: D i d you know him p e r c h a n c e ? D r . V. : Oh yes. D r . 0.: H i s s o n i s my Chief. Dr. V.: Is t h a t s o ? D r . 0.: Yes John B l a k e , J o h n B. Blake i s t h e Chief of t h e H i s t o r y of Medicine Div s i o n a t t h e N a t i o n a l L i b r a r y o f Medicine. D r . V.: Oh, i s t h a t s o , i s t h a t s o , how i n t e r e s t i n g . Yes, Blake w a s t h e r e i n t h e e a r l y d a y s , worked on pneumonia. The f i r s t c l i n i c a l prob- lem a t t a c k e d by t h e R o c k e f e l l e r H o s p i t a l w a s pneumonia and i t w a s v e r y much involved i n t h e epidemic of i n f l u e n z a and t h e pneumonia t h a t went 48 w i t h i t i n t h e 1918 f l u . In c o n n e c t i o n w i t h t h a t , I t h i n k one might s a y t h a t t h e R o c k e f e l l e r H o s p i t a l s t a r t e d modern oxygen t h e r a p y . D r . 0.: That's very interesting. D r . V.: It s t a r t e d t h i s way. Lundsgaard, t h e Dane t h a t came t o work w i t h me w a s i n t e r e s t e d i n blood oxygen and h e was a n i n s p i r i n g t y p e of i n d i v i d u a l ; he g o t everybody i n t e r e s t e d i n blood oxygen. One of t h e t h i n g s he was i n t e r e s t e d i n was c y a n o s i s and he worked o u t t h e c o n c l u - s i o n t h a t you g e t c y a n o s i s when t h e r e ' s f i v e grams of reduced hemoglo- b i n p e r hundred m l . of blood i n t h e c a p i l l a r y b l o o d , t a k i n g t h e c a p i l l a r y oxygen c o n t e n t as a mean between t h e venous and t h e a r t e r i a l . You c a n ' t g e t c y a n o s i s i f you have s e v e r e anemia b e c a u s e you d o n ' t have enough hemoglobin t h e r e t o make t h a t f i v e grams of reduced hemoglobin. Lunds- gaard and I w r o t e a monograph on c y a n o s i s and t h a t c o n c l u s i o n was p a r t of i t . The i n f l u e n z a epidemic came and t h e s e v e r e p a t i e n t s t h a t g o t t h e pneumonia t h a t complicated t h e f l u , t h e more s e v e r e o n e s were c y a n o t i c , and it was a v e r y g r a v e time. And S t a d i e , who was working w i t h me and a l s o working on t h e pneumonia s e r v i c e and knew of t h i s work t h a t Lunds- gaard w a s d o i n g , w a s i n t e r e s t e d t o see whether t h e s e c y a n o t i c p e o p l e were c y a n o t i c because t h e y c o u l d n ' t g e t oxygen i n t o t h e blood and t h e l u n g s o r because t h e y had a r e t a r d e d c i r c u l a t i o n . So he s t a r t e d d o i n g a r t e r i a l punctures. T h a t w a s t h e f i r s t time a r t e r i a l p u n c t u r e s were done i n what you might c a l l a c l i n i c a l s e n s e . A German had worked o u t t h e t e c h n i q u e on a n i m a l s . When Lundsgaard and I proposed t o D r . Cole t h a t we t r y i t on o u r s e l v e s , Cole s a i d , "No, t h a t ' s t o o r i s k y t o do it on human beings." 49 Well, S t a d i e g o t t h e i d e a , w h i l e D r . Cole w a s away on a n i n s p e c t i o n of army camp h o s p i t a l s , and h e d i d n ' t know t h a t i t w a s f o r b i d d e n , and I was home w i t h t h e f l u . When I g o t back, S t a d i e had a l r e a d y worked o u t t h e t e c h n i q u e on dogs and done it on h i m s e l f and o n one o r two p a t i e n t s , and I ha.d him do i t on m e and i t went a l l r i g h t . So, by t h e time Cole g o t back from t h e army camps, a r t e r i a l p u n c t u r e was a f a i t accompli: T h a t ' s t h e way i t g o t i n t o modern medicine. Well, S t a d i e v e r y q u i c k l y found t h a t when t h e s e p a t i e n t s g o t c y a n o t i c t h e r e w a s a l a c k of oxygen i n t h e i r a r t e r i a l b l o o d ; t h e y w e r e n ' t g e t t i n g oxygenation of t h e blood i n t h e l u n g s . And h e thought t h a t i t might be overcome by i n c r e a s i n g t h e oxygen c o n t e n t of the a i r t h e y b r e a t h e d . So t h e way i t happened, S t a d i e had had a n e d u c a t i o n a s mechanical e n g i n e e r b e f o r e he went i n t o medicine. So h e b u i l t a n oxygen chamber t h a t would h o l d two p a t i e n t s - - h o l d two beds. It was a i r - c o n d i t i o n e d - - t h a t was b e f o r e a i r c o n d i t i o n i n g was known, b u t i t was a i r - c o n d i t i o n e d so t h a t i t d i d n ' t g e t h o t , and h e had a r e g u l a r Goldberg arrangement t o a n a l y z e t h e oxygen a t i n t e r v a l s and a u t o m a t i c a l l y r e g u l a t e t h e inflow s o t h a t t h e oxygen would be k e p t where you wanted i t . W e l l , he found t h a t - - w e l l t o t a k e a t y p i c a l c a s e , a p a t i e n t w i t h 70 p e r c e n t oxygen s a t u r a t i o n of h i s a r t e r i a l blood i n s t e a d of a normal 98 p e r c e n t s a t u r a t i o n , would have m e n t a l d i s t u r b a n c e and t a c h y c a r d i a . When he w a s p u t i n t o t h e chamber w i t h 60 p e r c e n t oxygen i n t h e a i r h i s a r t e r i a l s a t - u r a t i o n went up t o o v e r 90 p e r c e n t h i s mind c l e a r e d and h i s h e a r t slowed down. D r . 0.: T h i s was w i t h o u t any a t t e m p t t o u s e a mask o r n a s a l t u b e s , 50 j u s t t h e environment, t h e i n n e r chambers. D r . V.: No, t h e i d e a w a s t h a t i n o r d e r t o f e e d , b a t h e , e t c e t e r a w i t h the l e a s t t i r i n g o f t h e p a t i e n t , t h e b e s t way was t o have a chamber. It was a l l g l a s s . You c o u l d s e e i n from anywhere. It was p u t i n a l a r g e ward chamber. I n t h e a i r w i t h 40 p e r c e n t oxygen, t h e a n o x i a would be immediately r e l i e v e d . I f t h e p a t i e n t w a s d e l i r i o u s h e would come o u t of t h e d e l i r i u m , h i s p u l s e ra e would come down. The oxygen d i d n ' t a f f e c t t h e c o u r s e of t h e i n f e c t o n , b u t it gave t h e p a t i e n t a chance t o f i g h t i t . He d i d n ' t have t o f i g h t s e v e r e a n o x i a t o g e t h e r w i t h the b a c t e r i a l toxin. The p a t i e n t ' s blood was a n a l y z e d f o r oxygen so t h a t i t was known what w a s happening. That work, I t h i n k , r e a l l y s t a r t e d a n a l y t i c a l l y c o n t r o l l e d prolonged oxygen t h e r a p y i n t h i s c o u n t r y , as a m a t t e r of f a c t , i n t h e world because i t h a d n ' t been used b e f o r e i n a s y s t e m a t i c way. It had been used i n a haphazard way by p u t t i n g a mask o v e r a p a t i e n t ' s nose and mouth and b u b b l i n g oxygen o u t of a t a n k , b u t w i t h o u t any a c c u r a t e knowledge o f what c o n c e n t r a t i o n of oxygen w a s b e i n g g i v e n and w i t h o u t a n a l y z i n g the blood f o r oxygen t o f i n d w h e t h e r anox- emia e x i s t e d , w h e t h e r i t w a s remedied by b r e a t h i n g oxygen-enriched a i r , and when t h e p a t i e n t ' s pulmonary c o n d i t i o n improved s o much t h a t he c o u l d be t a k e n o u t o f t h e chamber. On Long I s l a n d t h e r e ' s a C a t h o l i c h o s p i t a l , f o r c i r c u l a t o r y d i s e a s e s , between h e r e and New York, where t h e y have c h i l d r e n w i t h c o n g e n i t a l c a r d i a c t r o u b l e t h a t have a n o x i a from l e f t t o r i g h t c a r d i a c s h u n t s , and t h e y have a room t h e r e t h a t ' s modeled o n S t a d i e ' s t h a t w i l l h o l d f i v e k i d s a t once and t h e y keep them i n t h e r e f o r weeks. Well, you might s a y 51 t h a t was t h e r e s u l t of t h i s Dane, Lundsgaard, coming o v e r and g e t t i n g u s i n t e r e s t e d i n oxygen! D r . 0.: I t ' s amazing r e a l l y how many t h i n g s c a n come o u t of a p u r e l y happenstance o c c u r r e n c e . I mean, a n i n d i v i d u a l l i t e r a l l y knocking on your door s a y i n g h e r e I am! D r . V.: Yes. Lundsgaard w a s a g r e a t chap. Lundsgaard persuaded me t o work o u t f o r him t h e method f o r d e t e r m i n i n g oxygen i n t h e blood t h a t was used soon a f t e r w a r d s by S t a d i e . We l a i d o u t t h e o u t l i n e t o t h e book on c y a n o s i s by going down t o L a k e h u r s t , New J e r s e y f o r a week--Lundsgaard and I. We worked on t h e book e v e r y morning and p l a y e d g o l f e v e r y afternoon. By t h e end of t h e week we had t h e book o u t l i n e d ! D r . 0.: Yes, t h a t ' s l i s t e d h e r e , 1923. Dr. V.: It was r a t h e r a monograph t h a n a book a l t h o u g h i t w a s p u b l i s h e d i n book form. D r . 0.: While w e ' r e s p e a k i n g of t h e book, I u n d e r s t a n d Volume 2 o f Q u a n t i t a t i v e C l i n i c a l Chemistry h a s been r e p u b l i s h e d , d i d n ' t P e t e r s p u t o u t a second volume? I t ' s a m o d i f i c a t i o n o r s h o r t e n i n g o r something, b u t w a s t h e r e e v e r a n y t a l k o f a complete r e v i s i o n ? D r . V.: Yes. W e promised t h e p u b l i s h e r s we would keep up t h e r e v i s i o n of t h e whole t h i n g . I g o t so involved i n l a b o r a t o r y work, a l s o t h i s China medical work, t h a t I j u s t d i d n ' t do i t , much t o P e t e r s ' d i s g u s t . Even- t u a l l y I t o l d him t o go ahead w i t h t h e I n t e r p r e t a t i o n s . He a g r e e d t o t h a t and he s t a r t e d . Then h e s a i d I ' d have t o do t h e l a s t h a l f of i t 52 with t h e a c i d - b a s e b a l a n c e and t h e hemoglobin and oxygen which w a s prac i c a l l y based o n work which w a s m o s t l y done i n t h e R o c k e f e l l e r I n s t t u t e l a b o r a t o r y and I s a i d I would, and h e a g r e e d t o r e v i s e t h e firs half. W e l l , he c a r r i e d o u t h i s p a r t and r e v i s e d i t and I n e v e r d i d c a r r y o u t my p a r t . But t h e r e w a s s o much demand f o r t h e u n r e v i s e d second p a r t , which was t o a c o n s i d e r a b l e e x t e n t , a f i n i s h e d j o b , that the p u b l i s h e r s have r e c e n t l y r e p u b l i s h e d t h a t , t h e l a s t h a l f , w i t h o u t r e v i s i o n e x c e p t f o r c o r r e c t i o n o f a few e r r o r s . I f e e l v e r y much ashamed t h a t I n e v e r d i d do my j o b on t h a t b u t t h e war came a l o n g and the American Bureau f o r Medical Aid t o China and t h e n t h i s j o b a t Brookhaven o r g a n i z i n g t h e m e d i c a l department. D r . 0.: You were busy, t o s a y t h e l e a s t ! D r . V.: So I j u s t f a i l e d . And now t h e a p p l i c a t i o n s of c l i n i c a l chem- i s t r y a r e s o numerous t h a t nobody c o u l d w r i t e one book t o c o v e r t h e f i e l d . I a m engaged a t p r e s e n t on a book--a p u r e l y t e c h n i c a l book--to b r i n g t o g e t h e r i n one volume t h e v a r i o u s a p p l i c a t i o n s t h a t have b e e n made w i t h t h e o l d manometric g a s a n a l y s i s machine. A l o t o f t h i n g s have b e e n done w i t h i t i n v a r i o u s l a b o r a t o r i e s t h a t I never a n t i c i p a t e d i t would be used for. I t ' s used f o r e x t r a c t i n g and measuring g a s s e s f o r chromatography, f o r example. I ' v e g o t a man from a n o t h e r l a b o r a t o r y who's developed those methods t o w r i t e a b i g c h a p t e r on i t . D r . 0.: I ' m s u r e i t ' s d i f f i c u l t and p e r h a p s a l m o s t u n f a i r t o a s k you a q u e s t i o n l i k e t h i s , b u t , and I d o n ' t mean t o sound maudlin a t a l l , b u t what of t h i s v a s t amount of work t h a t you and your group have done do you 53 c o n s i d e r t h e most i m p o r t a n t , o r do you t h i n k any one group of e x p e r i - ments, as you l o o k back w i t h t h e p e r s p e c t i v e of t h e s u c c e e d i n g y e a r s , was p e r h a p s t h e c o n t r i b u t i o n t h a t ' s had t h e g r e a t e s t i m p a c t ? D r . V.: I presume t h e work t h a t had t h e most impact, because i t w a s taken up and a p p l i e d , w a s t h e work on t h e a c i d - b a s e b a l a n c e . The s e r i e s of p a p e r s t h a t we p u b l i s h e d on t h e blood g a s s e s and e l e c t r o l y t e s , i n - c l u d i n g t h a t one from Peking on t h e p h y s i c a l c h e m i s t r y o f t h e b l o o d , was more r e f i n e d and went f u r t h e r , b u t i t h a s n o t been u n d e r s t o o d t o t h e same e x t e n t ; t h a t i s , r e l a t i v e l y few p e o p l e would be a b l e t o t e l l you what t h a t Peking p a p e r was a b o u t . It goes i n t o t h e thermodynamics of t h e Donnan e q u i l i b r i u m and t h e b i o c h e m i s t s , a t t h e t i m e t h a t t h a t was p u b l i s h e d i n t h e e a r l y 192Os, most of them w e r e n ' t equipped t o a p - p r e c i a t e t h a t s o r t of t h i n g and p r o b a b l y never r e a d i t . But t h e a c i d - base work w a s needed. There was a n a p p l i c a t i o n - - y o u might s a y t h e r e was a vacuum t h a t i t f i l l e d . So t h a t i t p r o b a b l y had t h e most impact on i n t e r n a l medicine o f a n y t h i n g . Of c o u r s e , t h e work we d i d on r e n a l physiology and B r i g h t ' s d i s e a s e have been t a k e n up r a t h e r w i d e l y , t o o , and c l i n i c i a n s do u r e a c l e a r a n c e s and o t h e r c l e a r a n c e s a l l o v e r t h e world. D r . 0.: T h a t ' s a r o u t i n e h o s p i t a l l a b o r a t o r y procedure now. D r . V.: A t t h e t i m e , w h i l e I w a s s t i l l i n L e v e n e ' s l a b o r a t o r y , I worked o u t t h e n i t r o u s a c i d method f o r d e t e r m i n i n g amino a c i d s , a n d , w i t h t h e h e l p of Gustav Meyer, showed f o r t h e f i r s t time t h a t f r e e amino a c i d s a r e absorbed d u r i n g d i g e s t i o n and t h a t t h e r e a r e enough absorbed t o 54 account f o r n i t r o g e n metabolism. T h a t had a marked impact o n p h y s i o l o g y a t the time. I d o n ' t t h i n k i t e v e r a f f e c t e d c l i n i c a l medicine. There had been so much work done, and s i n c e chromatographic methods f o r micro- d e t e r m i n a t i o n s of amino a c i d s have come o u t - - s o much of t h a t - - t h a t I t h i n k i t ' s o n l y a n o c c a s i o n a l h i s t o r i c a l r e v i e w t h a t would r e c a l l t h a t work t h a t Meyer and I d i d . T h a t came o u t a b o u t 1912. It i s n ' t v e r y o f t e n t h a t a p i e c e o f work i s remembered f o r more t h a n a decade. D r . 0.: I t ' s r a t h e r amazing. This is so true. You l o o k a t b i b l i o g - r a p h i e s of p a p e r s w r i t t e n today and one a l m o s t g e t s t h e i m p r e s s i o n t h a t they d o n ' t want t o have a r e f e r e n c e which goes t o , s a y e a r l i e r sometimes t h a n 1964 o r 63, so you know e v e r y t h i n g h a s t o b e b u i l t from t h e l a t e s t building blocks. Dr. V.: I ' v e been shocked t o e n c o u n t e r two o r t h r e e W.D. chemists t h a t d i d n ' t know who E m i l F i s c h e r w a s ' Modern ones. He w a s t h e w o r l d ' s g r e a t e s t c h e m i s t i n h i s day and h e d i d enough t o make f i v e d i f f e r e n t men immortal. H i s work on t h e a n i l i n e d y e s ; he worked o u t t h e s t r u c t u r e o f the purines, t h e pyrimidines. He worked o u t t h e s t r u c t u r e s of t h e s u g a r s o n which a l l s u g a r work i s based. He demonstrated t h e amino a c i d c o n s t i - t u t i o n of t h e p r o t e i n s and i n h i s l a t e r y e a r s , he worked on t h e c h e m i s t r y of t h e t a n n i c a c i d s e r i e s o f compounds. D r . 0.: I t ' s a r a t h e r sad commentary. I t ' s t r u e i n medicine, t o o , t h a t everybody's i n s u c h a h u r r y t o l e a r n new t h i n g s and develop new t h i n g s seemingly. 55 D r . V.: T h e r e ' s j u s t so much t o l e a r n . You could keep up w i t h s c i e n c e f i f t y y e a r s ago when I s t a r t e d . F o r a number of y e a r s I a b s t r a c t e d t h e Biochemische Z e i t s c h r i f t and Z e i t s c h r i f t f u r P h y s i o l o g i a e t Chemie. Those two j o u r n a l s had a l m o s t a l l t h e b i o c h e m i s t r y t h e r e w a s i n them, and one man c o u l d a b s t r a c t them f o r t h e American Chemical S o c i e t y . Now I c o u l d n ' t a b s t r a c t t h e J o u r n a l of B i o l o g i c a l Chemistry. Some of t h e papers i n v o l v e e l a b o r a t e t e c h n i q u e s t h a t I have n e v e r used and c o u l d n ' t understand. T h a t i s , I ' m n o t c a p a b l e o f c o v e r i n g e v e r y t h i n g t h a t comes o u t i n b i o c h e m i s t r y , which I w a s a b l e t o do i n t h e e a r l y y e a r s . D r . 0.: D i d you ever f e e l a t any time t h a t n o t having a n M.D. was a h i n d r a n c e as you were working more and more i n t h e f i e l d of c l i n i c a l b i o - chemistry? D r . V.: W e l l , I d o n ' t t h i n k i t w a s a r e a l h i n d r a n c e because I always had good M.D. men t o c o l l a b o r a t e w i t h . I would have been g l a d t o have a n M.D. t r a i n i n g , but i t would have t a k e n s i x y e a r s a d d i t i o n a l and d u r - i n g t h o s e s i x y e a r s I made a n a w f u l l o t of p r o g r e s s i n b i o c h e m i s t r y . I had enough b i o l o g y s o t h a t working w i t h men t h a t were t r a i n e d i n m e d i c i n e , I could u n d e r s t a n d what t h e y were doing, And, as a m a t t e r of f a c t , I became a p r e t t y good c l i n i c i a n o n B r i g h t ' s d i s e a s e ! I made t h e rounds regularly. A f t e r w a r d s , i n two o r t h r e e p a p e r s t h a t have come o u t under my name t h a t were l e c t u r e s , t h e M.D. was added w i t h o u t my knowing i t : One of them was b e f o r e t h e American C o l l e g e of I n t e r n a l Medicine, i n Chicago. I gave a l e c t u r e o n shock k i d n e y and w a s g r a n t e d what you might c a l l a n h o n o r a r y M.D. when i t came o u t w i t h my name on i t . I d i d g e t h o n o r a r y M.D.s from 56 two f o r e i g n u n i v e r s i t i e s , O s l o and Amsterdam, which p l e a s e d me v e r y much. D r . 0.: Well, I c e r t a i n l y d i d n ' t mean t o i n t i m a t e i n any way t h a t you should have. I w a s j u s t c u r i o u s t o see how you f e l t o r would r e a c t t o t h a t q u e s t i o n b e c a u s e God knows, i t would have been " g i l d i n g t h e l i l y " - - - I mean, i t w a s n ' t something o b v i o u s l y n e c e s s a r y t o have. D r . V.: I would have been g l a d t o have i t , b u t it would have c u t o u t s e v e r a l y e a r s of v e r y v a l u a b l e e x p e r i e n c e i n b i o c h e m i s t r y . D r . 0.: Alma H i l l e r w a s t h e a s s o c i a t e i n your l a b o r a t o r y f o r some y e a r s , was s h e n o t ? D r . V.: Yes. She was w i t h m e 30 y e a r s . She came--1 t h i n k it w a s a b o u t 1916 o r 1918--and s h e s t a y e d w i t h m e u n t i l I r e a c h e d t h e r e t i r i n g a g e i n '48. She had a B a c h e l o r ' s d e g r e e i n c h e m i s t r y and s h e t o o k a Ph.D. at Columbia w h i l e s h e c o n t i n u e d working w i t h me. She r e a l l y r a n t h e c l i n i c a l l a b o r a t o r y - - - - a f t e r we developed what you c o u l d c a l l a " C l i n i c a l l a b " she r e a l l y r a n i t . D r . 0.: I n o t h e r words, t h e s e r v i c e l a b o r a t o r y , a s i t w e r e , f o r the R o c k e f e l l e r H o s p i t a l , f o r t h e r o u t i n e c l i n i c a l l a b work. D r . V.: Yes, and s h e a l s o d i d r e s e a r c h work. She was a good chemist. D r . 0.: L. E. F a r r . Is t h i s t h e same D r . F a r r who came h e r e t o Brook- haven? D r . V.: Yes. 57 D r . 0.: He was w i t h you i n t h e t h i r t i e s , w a s n ' t h e ? Dr. V.: Yes. He l e f t t o become head of t h e A l f r e d I. Du Pont I n s t i t u t e i n Wilmington, and when I t o o k o v e r t h e j o b of o r g a n i z i n g a m e d i c a l department h e r e , I g o t him t o l e a v e Wilmington and come o u t h e r e as head o f t h e Medical Department. Dr. 0.: I w a s j u s t l o o k i n g through y o u r b i b l i o g r a p h y and I s e e t h i s paper by P h i l l i p s , Van S l y k e , e t a1 which i s a n o t h e r s t a n d a r d i n t h e blood bank. Dr. V.: The c o p p e r s u l f a t e method? D r . 0.: Yes. To t e s t someone's hemoglobinwhen t h e y came t o g i v e blood. D r . V. Yes. T h i s i s how i t happened. The war broke o u t and I was c a l l e d t o Washington on a committee t o t a l k o v e r t h i n g s t h a t were needed i n t h e army medical h o s p i t a l s f o r f i e l d s e r v i c e . It o c c u r r e d t o me t h a t a spec f i c g r a v i t y method f o r blood c o n c e n t r a t i o n would be u s e f u l . Drop- ping methods had long been known u s i n g m i x t u r e s of o r g a n i c l i q u i d s s u c h as benzene and chloroform. Chloroform b e i n g heavy and benzene l i g h t , one can make a s e r i e s of m i x t u r e s of v a r y i n g s p e c i f i c g r a v i t y . The m i x t u r e i n which a d r o p of blood n e i t h e r r i s e s o r f a l l s h a s t h e same s p e c i f i c g r a v i t y as t h e blood. However, such o r g a n i c m i x t u r e s were n o t p r a c t i c a l f o r f i e l d s e r v i c e because t h e y have t e m p e r a t u r e c o e f f i c i e n t s a b o u t f i v e times a s g r e a t a s t h a t of water o r blood. They g i v e a c c u r a t e r e s u l t s o n l y i f used w i t h a c o n s t a n t t e m p e r a t u r e b a t h . We needed t o have g r a v i t y s t a n d a r d s i n t h e form of w a t e r s o l u t i o n s . But a d r o p of b l o o d f a l l i n g 58 i n t o a s o l u t i o n of sodium c h l o r i d e , f o r example, d i s i n t e g r a t e s . My f i r s t i d e a w a s t o u s e sodium c h l o r i d e s o l u t i o n s c o n t a i n i n g p i c r i c a c i d , which would form a s a c k of p r o t e i n p r e c i p i t a t e around t h e blood s o t h a t i t would n o t d i s i n t e g r a t e . It worked a l l r i g h t . But t h e n e x t morning P h i l l i p s w i t h a c o p p e r s u l f a t e s o l u t i o n , which was j u s t one s u b s t a n c e d i d t h e same t h i n g . It a l s o had t h e a d v a n t a g e of h a v i n g a c h a r a c t e r i s t i c c o l o r , so t h a t one would know what w a s i n t h e b o t t l e , and copper s u l f a t e s o l u t i o n s t u r n e d o u t t o have t h e same t e m p e r a t u r e c o e f f i c i e n t s e x a c t l y a s t h e blood o r plasma i n which t h e y b a l a n c e d So we developed t h e copper s u l f a t e method f o r blood s p e c i f i c g r a v t y . From t h e g r a v i t y of plasma one c o u l d e s t i m a t e t h e c o n c e n t r a t i o n p asma p r o t e i n s , and from t h e g r a v i t y of whole blood one c o u l d e s t i m a t e t h e c o n c e n t r a t i o n of hemo- globin. So we developed t h e copper s u l f a t e method. It w a s adopted by t h e armed s e r v i c e s o f b o t h o u r c o u n t r y and B r i t a i n , and w a s used e s p e - c i a l l y t o a s s a y t h e e f f e c t s of shock and hemorrhage i n wounded men. The way i n which i t came t o be a p p l i e d by the Red Cross t o t e s t blood donors is i n t e r e s t i n g . I w a s on t h e Blood Bank Comnittee, which d e c i d e d t h a t 12 grams o f hemoglobin p e r 100 m l . below which blood would n o t be drawn from a donor. R e p o r t s came i n from a l l o v e r t h e United S t a t e s c o n c e r n i n g t h e p e r c e n t a g e o f v o l u n t e e r donors t h a t had t h e r e q u i r e d c o n c e n t r a t i o n o f hemoglobin. Some c i t i e s r e p o r t e d r e f u s a l of v e r y f e w donors and o t h e r s r e p o r t e d s o many r e j e c t i o n s t h a t i t looked as though t h e y had a n epidemic o f anemia. It was a p p a r e n t t h a t t h e v a r i a t i o n s were p r o b a b l y due t o e r r o r s i n t h e v a r i o u s methods f o r hemoglobin d e t e r m i n a t i o n . We adopted one copper s u l f a t e s t a n d a r d t h a t would b a l a n c e blood t h a t had 1 2 grams of hemoglobin p e r 100 m l . I f a drop of blood f e l l t o t h e bottom 59 of t h e s o l u t i o n t h e hemoglobin was above 12 grams and t h e donor was acceptable. The s t a n d a r d s o l u t i o n s w e r e s e n t from a c e n t r a l l a b o r a t o r y a l l over t h e country. A l l t h e g e o g r a p h i c a l d i f f e r e n c e s i n hemoglobin disappeared. The t e s t was j u s t a m a t t e r of drawing a drop o f blood from a f i n g e r o r e a r and l e t t i n g i t f a l l i n t o t h e c o p p e r s u l f a t e s o l u t i o n . I f t h e d r o p sunk you w e r e a donor. P h i l l i p s was a g r e a t f e l l o w . He h a s been working f o r s e v e r a l y e a r s on c h o l e r a i n t h e O r i e n t . D r . 0.: Yes I n t h e Naval Medical Research U n i t i n T a i p e i . Dr. v.: Yes I went o u t t h e r e i n ' 6 1 and worked w i t h him f o r a few months. He s b o t h a b e a u t i f u l l a b o r a t o r y worker h i m s e l f and a g r e a t o r g a n i z e r of teamwork. The s u c c e s s o f t h e method t h a t he developed f o r t r e a t i n g c h o l e r a was e x t r a o r d i n a r y . I n t h e o l d d a y s , c h o l e r a was p r a c - t i c a l l y s u r e d e a t h i f one was n o t t r e a t e d , and 60 p e r c e n t chance of d e a t h i f one g o t t h e b e s t h o s p i t a l t r e a t m e n t . I remember r e a d i n g a n o l d h e a l t h r e p o r t from t h e P h i l i p p i n e I s l a n d s where t h e m o r t a l i t y from c h o l e r a was g i v e n a s 99 p e r c e n t . I n h o s p i t a l s where P h i l l i p s ' t r e a t m e n t w a s applied there was almost zero mortality. Even p a t i e n t s t h a t were brought i n p r a c t i c a l l y moribund, r e c o v e r e d . They were i n f u s e d w i t h t h e s p e c i a l p h y s i o l o g i c a l s o l u t i o n of s a l t s , t h a t P h i l l i p s had worked o u t t o r e p l a c e losses. The i n f u s i o n was c o n t i n u e d u n t i l t h e s p e c i f i c g r a v i t y of t h e blood, t a k e n w i t h t h e copper s u l f a t e method, w a s lowered t o normal, i n d i c a t i n g t h a t t h e d e s i c c a t i o n had been c o r r e c t e d . D r . 0.: T h i s was by c a r e f u l m o n i t o r i n g of t h e i r e l e c t r o l y t e s , w a t e r - b a l a n c e and s o on. 60 Dr. V.: Yes. He had worked o u t t h e r e l a t i v e l o s s e s of p o t a s s i u m , sodium, magnesium, c a l c i u m , c h l o r i d e and b i c a r b o n a t e t h a t t h e y l o s t i n their stools. D r . 0.: I s h o u l d have s a i d t h a t good r e p l a c e m e n t then. D r . V.: Yes, h e ' d worked o u t a r o u t i n e of good r e p l a c e m e n t , a s o l u t i o n , you might s a y . And h e ' d g i v e enough t o b r i n g t h e s p e c i f i c g r a v i t y of t h e blood down where i t ought t o b e ; t h e s p e c i f i c g r a v i t y would be v e r y h i g h because of d e s i c c a t i o n . He p u t t h e p a t i e n t o n a n army c o t , which was n o t h i n g b u t a s t r e t c h o f c a n v a s , w i t h a h o l e i n i t b e n e a t h t h e anus and a p a i l b e n e a t h t h a t , and t h e n r u n t h e s o l u t i o n i n as f a s t as t h e patient ran it out i n the pail. And t h e y p r a c t i c a l l y a l l recovered! H i s p r i z e p a t i e n t t o o k 80 l i t e r s i n f o u r days! But you cou d d i e i n a few h o u r s from d e s i c c a t i o n . You go i n t o shock and you j u s t d i e . Plain desiccation. The e x t r a o r d i n a r y t h i n g was t h a t none of P h i l i p s ' crew caught t h e c h o l e r a . H e ' d have a b o u t a dozen men t h a t would go t o M a n i l a , f o r example, and s e t u p a u n i t t o h a n d l e t h e s e p a t i e n t s . You c o u l d n ' t handle them under t h e c o n d i t i o n s w i t h o u t a chance of g e t t i n g f e c e s o n your hands. You c o u l d n ' t h a n d l e them. B u t none of t h e crew g o t i t and v e r y few Europeans g o t i t and P h i l l i p s ' e x p l a n a t i o n was t h a t i f you were i n a good s t a t e of n u t r i t i o n you had r e s i s t a n c e t o t h a t t y p e of c h o l e r a t h a t was going around. T h a t d o e s n ' t a p p l y t o e v e r y k i n d of c h o l e r a . I n 1911, when I came back from F i s c h e r ' s l a b o r a t o r y - - I made a t r i p through Europe and came back from N a p l e s , stopped a t Rome o n t h e way. The second day we were i n Rome we were t o l d t h a t c h o l e r a had b r o k e n o u t t h e f i r s t day we were t h e r e , i n a c e r t a i n s e c t i o n of Rome, and t h a t t h e n e x t day 61 80 p e r c e n t m o r t a l i t y ! I t h o u g h t I had i t myself! A f t e r we g o t on t h e b o a t , everybody had t o t e l l where h e w a s f o r t e n days and s o f o r t h and i t was r a t h e r e x p e c t e d . W e l l , t h e second day o u t I woke up w i t h d i a r r h e a and t h a t r i c e w a t e r s t o o l and wondered w h e t h e r I ' d be a l i v e i n t h e morn- ing when t h e s h i p ' s s u r g e o n came around. He w a s t h i s f e l l o w I t o l d you about. He j u s t f e l t me and he s a i d , "No, you h a v e n ' t g o t c h o l e r a ; you'd be c o l d . You're warm!" It t u r n e d o u t t h e r e were bad o y s t e r s t h a t had been brought from New York and were b e i n g used on t h e way back. There were q u i t e a l o t of p e o p l e who came down w i t h i t . But t h a t w a s t r u e . T h i s d e s i c c a t i o n b r i n g s on a s t a t e of shock and you s h u t down your---- D r . 0.: P e r i p h e r a l v a s c u l a r system. D r . V.: - - - - -p e r i p h e r a l v a s c u l a r s y s t e m and you g e t c o l d . D r . 0.: I u n d e r s t a n d John P l a z i n was your t e c h n o l o g i s t f o r many, many y e a r s a t t h e I n s t i t u t e and t h e n came h e r e w i t h you t o Brookhaven. Dr. V.: Yes. He was a l r e a d y i n t h e H o s p i t a l when I moved i n . Canby Robinson, I t h i n k , had brought him i n . I d o n ' t know how Canby came t o p i c k him up because h e had o n l y a h i g h s c h o o l e d u c a t i o n and he knew a l i t t l e c h e m i s t r y , b u t he w a s a n a t u r a l born t e c h n i c i a n . He c o u l d do f i n e mechanics. I t a u g h t him g l a s s b l o w i n g . I was a p r e t t y good g l a s s - blower by t h e time I t o o k my d e g r e e a t Ann Arbor. I t a u g h t him g l a s s - blowing and w i t h i n a y e a r he was s o much b e t t e r t h a n I t h a t I n e v e r d i d any more! Immensely d i g n i f i e d man. Read t h e b e s t l i t e r a t u r e and en- joyed t h e b e s t music. E s s e n t i a l l y a gentleman and a s c h o l a r d e s p i t e t h e f a c t t h a t h e n e v e r had a c o l l e g e e d u c a t i o n : H e w a s w i t h m e a.11 t h e time 62 I was a t t h e R o c k e f e l l e r and t h e n he came w i t h me o u t h e r e and h e w a s h e r e u n t i l j u s t a s I g o t back from Taiwan a t C h r i s t m a s , '61. He f i n i s h e d a w e e k ' s work and h e d i d n ' t show up Monday morning and I went o v e r t o h i s house and h e was dead on h i s couch w i t h t h e p a p e r b e s i d e him: H i s wife had d i e d some y e a r s b e f o r e so he was l i v i n g by h i m s e l f . D r . 0.: T h e r e ' s one q u e s t i o n I would l i k e t o a s k which more o r l e s s comes t o mind any time t h a t one s e e s somebody who h a s s p e n t a s much time a s you have a t a s i n g l e i n s t i t u t i o n . You o b v i o u s l y , o v e r t h e c o u r s e of y e a r s , had many o p p o r t u n i t i e s and a p p r o a c h e s , I ' m s u r e , t o go t o v a r i o u s universities. I g u e s s t h e r e a s o n f o r n o t doing so w a s b e i n g q u i t e s a t i s f i e d w i t h t h e l a b o r a t o r y s i t u a t i o n you had a t t h e R o c k e f e l l e r . D r . V.: Yes, I had e v e r y t h i n g I wanted t o work w i t h and complete freedom t o do what I wanted. The most d i f f i c u l t t h i n g t o r e f u s e was a n i n v i t a - t i o n t o go back t o my alma m a t e r , Ann A r b o r , a s Dean of t h e M e d i c a l School and P r o f e s s o r of Biochemistry. A s I s a i d , my f a t h e r was o n t h e f a c u l t y t h e r e when I w a s born and I p l a y e d i n t h e s t r e e t s of Ann Arbor when I w a s a c h i l d . I g r a d u a t e d t h e r e and my f i r s t w i f e g r a d u a t e d t h e r e , and s e n t i m e n t a l a t t a c h m e n t s were v e r y s t r o n g . I knew most of t h e men on t h e m e d i c a l f a c u l t y a t t h e time and t h e y were v e r y c o r d i a l i n t h e i r i n - vitation. I agonized o v e r i t f o r a c o u p l e of months and f i n a l l y d e c i d e d t h a t I ' d keep on w i t h t h e work I had going. I w a s a l i t t l e a f r a i d of a d m i n i s t r a t i v e work because a good a d m i n i s t r a t o r h a s t o know how t o s a y lln0ll and I h a t e t o do t h a t . D r . 0.: D i d n ' t you, as t h e head of your l a b o r a t o r y , though, have t o o c c a s i o n a l l y s a y no, i n a s e n s e ? 63 D r . V.: Oh, p r a c t i c a l l y not. There were j u s t a bunch of u s working together. I f one of my men g o t a n i d e a t h a t I t h o u g h t w a s n ' t a n y good, I l e t him f i n d i t o u t f o r h i m s e l f and sometimes he was r i g h t ! D r . 0.: You s t a y e d on a t t h e Rockefel e r I n s t i t u t e u n t i l t h e compulsory age f o r r e t i r e m e n t ? D r . V.: They had a compulsory a g e f o r r e t i r e m e n t a t 65, b u t 1 c o u l d have s t a y e d on as a n e m e r i t u s w i t h my aboratory but without patients, and I e x p e c t e d t o do t h a t b u t the c h a l l e n g e t o come o u t here and g e t a new R o c k e f e l l e r I n s t t u t e s t a r t e d a t Brookhaven was a t t r a c t i v e and s o I r o s e and took t h e ba t. [End of S i d e I , Reel 21 [ S i d e 11, Reel 21 Dr. 0.: Would you d e s c r i b e D r . Dochez? D r . V.: A d e l i g h t f u l fellow. He w a s v e r y a t t r a c t i v e . He was a b a c h e l o r a l l h i s l i f e and w a s most p o p u l a r a s a g u e s t f o r weekends o r any o t h e r occasion. He never seemed t o r e a d v e r y much b u t he always knew t h e l i t - erature. He seemed t o be a b l e t o l i e down o n a couch w i t h a book on h i s c h e s t and wake up and know e v e r y t h i n g t h a t was i n it! D r . 0.: That's a talent! Dr. V.: He had one of t h e s e a b s o l u t e l y c l e a r minds. There was no con- f u s i o n i n any of h i s t h o u g h t s . He l i v e d w i t h Avery a s l o n g as Avery s t a y e d i n New York. They had a n a p a r t m e n t f o r t h r e e men and v a r i o u s 64 c o l l e a g u e s were w i t h them f o r s h o r t e r o r l o n g e r t i m e s and t h e n t h e y would g e t m a r r i e d , one a f t e r t h e o t h e r , b u t n e i t h e r Avery nor Dochez ever m a r r i e d . I remember s t a y i n g w i t h them one n i g h t . Dochez seemed t o f e e l r a t h e r g u i l t y t h a t he w a s somewhat a c t i v e s o c i a l l y a s w e l l as scientifically. And t h i s was a F r i d a y n i g h t and Dochez had a c c e p t e d a n i n v i t a t i o n f o r t h e weekend and i t b o t h e r e d h i s c o n s c i e n c e a g r e a t d e a l t h a t he s h o u l d be w a s t i n g h i s time on t h i n g s l i k e t h a t and b e s i d e s t h a t he w a s s u r e t h a t h e ' d be b o r e d and h e t h o u g h t h e ' d c a l l up and t e l l them he w o u l d n ' t come anyway. T h i s would be a w a s t e d weekend. No way f o r a man t o spend h i s t i m e on t h i n g s l i k e t h a t . A t t h e same t i m e , Dochez was packing h i s s u i t c a s e ! A f t e r a w h i l e Avery went t o t h e t e l e p h o n e and c a l l e d a t a x i t o t a k e "DO"' (Laughter) D r . 0.: I g a t h e r Avery w a s known as " t h e Fess". D r . V.: Avery w a s known as "Fess". He a l s o had a n e x t r a o r d i n a r i l y c l e a r mind. He w a s a n a t u r a l b o r n comedian, F e s s w a s . D r . 0.: One l o o k i n g a t h i s photograph, you w o u l d n ' t t h i n k t h a t . He looks v e r y s t u d i o u s . Very s c h o l a r l y . D r . V.: I remember one time he i m i t a t e d a chimpanzee t h a t w a s b e i n g t r i e d o u t by a p s y c h o l o g i s t t o s e e how t h e chimpanzee would f i g u r e on how t o g e t a banana i n a cage where he had t o r e a c h w i t h a s t i c k under t h e cage door t o g e t it. And it was a c o n v u l s i o n t o s e e Avery t a k e t h a t chimpanzee o f f . He c o u l d make a comic s t r i p o u t of most a n y t h i n g t h a t had something amusing t o i t . P e r f e c t l y deadpan! 65 M . 0.: Could you g i v e y o u r i m p r e s s i o n s of D r . Jacques Loeb? D r . V.: Yes. Well i n Loeb's t i m e , you might s a y t h e r e were two s c h o o l s of b i o l o g i c a l thought. One s c h o o l t h o u g h t t h a t l i v i n g organisms were o r g a n i z a t i o n s based on t h e laws o f p h y s i c s and c h e m i s t r y and t h a t i f you knew a l l a b o u t them you would u n d e r s t a n d how t h e y work. Loeb belonged t o t h a t school. It w a s a l m o s t a r e l i g i o n w i t h him. The o t h e r s c h o o l of thought w a s t h a t of John S c o t t Haldane, t h e g r e a t E n g l i s h p h y s i o l o g i s t who d i d a l l t h e work on t h e blood g a s s e s and a l t i t u d e and d i v i n g and s o forth. Magni i c e n t man! Haldane thought t h a t t h e r e was some kind o f v i t a l p r i n c i p e t h a t l i v i n g c e l l s had t h a t we d i d n ' t know a b o u t - - t h a t was n o t e x p l a n a b l e . It was something l i k e t h e d i f f e r e n c e between N i e l s Bohr and E i n s t e i n . N i e l s Bohr f e l t t h a t i n t h e o r g a n i z a t i o n of atoms t h e r e were t h i n g s t h a t you c o u l d f i n d o u t and e x p r e s s m e c h a n i c a l l y , b u t you c o u l d n e v e r make a m e n t a l p i c t u r e of how t h e y work. You c o u l d know what w a s going on and w r i t e f o r m u l a s t h a t would e x p r e s s i t , b u t e x a c t l y what made i t a l l go on, Bohr t h o u g h t we p r o b a b l y would n e v e r know t h a t , w h i l e E i n s t e i n was more o p t i m i s t i c . E i n s t e i n thought t h a t t h e r e was a n u l t i m a t e t r u t h and t h a t i f you knew i t a l l , you could make a p i c t u r e of it. I u n d e r s t a n d t h a t a t P r i n c e t o n t h e y had v e r y f r i e n d l y arguments about i t . W e l l , Haldane f e l t t h a t t h e r e was a n e s s e n c e of l i f e , o r whatever you c a l l i t , t h a t i s e s s e n t i a l f o r l i v i n g c e l l s , and t h i s c a n ' t be d e f i n e d o n t h e laws o f p h y s i c s and c h e m i s t r y , w h i l e Loeb f e l t t h a t i f you knew enough a b o u t i t t h a t you c o u l d so d e f i n e i t . And Loeb's o b j e c t i n l i f e - - a t l e a s t one of h i s o b j e c t s i n l i f e - - w a s t o work o u t t h e phys- i c a l and chemical e x p l a n a t i o n s of what goes on i n c e l l s as f a r as you L 66 c o u l d , and c o n t r a c t t h e a r e a of t h e unknown. The i d e a w a s t h a t even- t u a l l y you might e l i m i n a t e it. But a t any r a t e , i f you c a n g e t p h y s i c a l and chemical e x p l a n a t i o n s of v a r i o u s mechanisms i n t h e c e l l , you have added w e i g h t t o t h e h y p o t h e s i s t h a t e v e n t u a l l y s u c h t h i n g s a r e e x p l a i n - a b l e i f you c o u l d f i n d o u t enough, and p e r h a p s make p r o g r e s s towards f i n d i n g such a n e x p l a n a t i o n . D r . 0.: It's interesting. Along t h e s e l i n e s , a n o t h e r f i g u r e of t h i s p e r i o d , A l e x i s C a r r e l , a t l e a s t i n h i s l a t e r y e a r s became v e r y i n t e r e s t e d i n a l m o s t a m y s t i c a l philosophy. D r . V.: Yes, C a r r e l had a m y s t i c s t r e a k i n h i m . Sometimes, s i t t i n g w i t h C a r r e l a t l u n c h , h e would t a l k a b o u t some of t h e s e p e c u l i a r t h i n g s and seemed t o have a t w i n k l e i n h i s eye. I n e v e r r e a l i z e d t h a t h e took i t s o s e r i o u s l y u n t i l h i s book Man t h e Unknown came o u t , t h e n I r e a l i z e d t h a t h e d i d t a k e i t s e r i o u s l y ; t h a t t h i s m y s t i c t h i n g w a s r e a l t o him. D r . 0.: I c a n ' t remember t h e d a t e of p u b l i c a t i o n of t h a t book. Was i t a f t e r he l e f t t h e R o c k e f e l l e r and r e t u r n e d t o F r a n c e ? D r . V.: I t h i n k h e was s t i l l a t t h e R o c k e f e l l e r , b u t I ' m n o t s u r e . He d i d n ' t go back t o F r a n c e t o s t a y u n t i l t h e war came on and t h e n h e went back t o t a k e p a r t i n t h a t . Oh, I may be wrong a b o u t t h a t , b u t i t w a s about t h a t t i m e . Dr. 0.: Was h e somewhat of a r e c l u s e , o r w a s h e f a i r l y o u t g o i n g ? D r . V.: Well, i t would be d i f f i c u l t t o d e s c r i b e him e i t h e r way. He belonged t o t h e Century Club--had f r i e n d s t h e r e . He had f r i e n d s i n t h e 67 medical p r o f e s s i o n . H e had a good many v i s i t o r s from abroad. He remained completely F r e n c h , a l t h o u g h he s p e n t t h e l a s t 40 y e a r s of h i s l i f e i n t h i s c o u n t r y , and he owned a n i s l a n d o f f t h e c o a s t of B r i t t a n y . He used t o go back t h e r e e v e r y summer. He d i d h i s work mornings. He'd come a t 8 o ' c l o c k i n the morning and work u n t i l a b o u t 1 o ' c l o c k and he w a s n o t a v a i l a b l e t o telephone o r anything e l s e then. I n t h e a f t e r n o o n h e ' d do h i s r e a d i n g and w h a t e v e r t h i n g s came on. But h e ' d come down t o l u n c h u s u a l l y about 1 o'clock--a l i t t l e a f t e r everybody e l s e - - a n d go t o a c e r - t a i n t a b l e w i t h some of h i s a s s i s t a n t s and s i t t h e r e . He d i d n ' t make much e f f o r t t o mix w i t h o t h e r p e o p l e , b u t on some o c c a s i o n s when I d i d make i t a p o i n t t o s i t down w i t h him, I always had a v e r y p l e a s a n t lunch- eon c o n v e r s a t i o n and h e w a s always v e r y f r i e n d l y . One of Levene's e a r l y a s s i s t a n t s , a p h y s i c a l c h e m i s t , Heimrod, l o s t t h e s i g h t of b o t h eyes--he w a s h e a t i n g a s o l u t i o n , a l k a l i n e s o l u t i o n , and i t s p u r t e d and g o t d r o p s o f a l k a l i n e i n e a c h eye. Levene was i n t h e n e x t room and r a n i n and washed h i s e y e s o u t as q u i c k a s p o s s i b l e , took him o v e r t o a h o s p i t a l , b u t t h e a l k a l i p e n e t r a t e d one eye and he l o s t t h e s i g h t i n t h a t r a t h e r soon. A l k a l i p e n e t r a t e s t h e tissues--you could g e t a c i d on your s k i n and i n your e y e s and i t c o a g u l a t e s t h e t i s s u e s , b u t a l k a l i j u s t keeps e a t i n g i n . And he l o s t t h e o t h e r eye a month l a t e r . Well, h e was g i v e n a p e n s i o n and h e went o v e r t o Germany--he had t a k e n h i s Ph.D. i n Germany and most of h i s s c i e n t i f i c f r i e n d s were German, h i s f a t h e r w a s German-born--so he went o v e r t h e r e and l i v e d t h e r e s t of his life. When I was o v e r t h e r e i n 1911, h i s f a t h e r was Consul i n B a s e l . And I h e a r d t h a t Heimrod was t h e r e v i s i t i n g h i s f a t h e r . So when I g o t through w i t h my work i n B e r l i n , on o u r way down t o I t a l y we stopped o f f 68 a t B a s e l t o s e e Heimrod and we met C a r r e l t h e r e ! C a r r e l had l e f t h i s i s l a n d o u t i n B r i t t a n y and gone t o have a v i s i t w i t h Heimrod. I h e a r d t h a t C a r r e l o r i g i n a l l y l e f t F r a n c e because he s a i d a p p a r e n t l y p u b l i c l y t h a t h e d i d n o t know any e x p l a n a t i o n f o r some of t h e m i r a c l e s a t t h e S h r i n e a t Lourdes where p e o p l e went and g o t cured o f t h e i r i l l s and threw away t h e i r c r u t c h e s , That makes him p e r s o n a non g r a t a w i t h t h e e n t i r e French m e d i c a l p r o f e s s i o n . I d o n ' t know whether i t was t r u e o r not--that's n o t o f f i c i a l - - b u t I h e a r d t h a t t h a t was t h e r e a s o n why he g o t o u t of F r a n c e . D r . 0.: T h i s would have been p r i o r t o coming t o t h e United S t a t e s ? Dr. V.: Yes. He was o u t of Chicago, I t h i n k , b e f o r e h e came t o t h e Roc ke f e 1l e r D r . 0.: Yes. I seem t o remember t h i s , t o o ; f o r a v e r y b r i e f p e r i o d . How a b o u t Peyton Rous? Dr. V.: Well, P e y t o n - - h i s l i n e of work was q u i t e d i f f e r e n t from mine, of c o u r s e . He w a s a v e r y charming luncheon companion. I f you s a t next t o Peyton you'd be s u r e t h a t some r e a l l y i n t e r e s t i n g t o p i c would a r i s e and t h a t Peyton would make i t i n t e r e s t i n g . And a n a w f u l l y n i c e f e l l o w . Very s i n c e r e . H a r d working. The men t h a t worked w i t h him swore by h i m . He came t o t h e I n s t i t u t e j u s t a b o u t t h e same time I d i d , maybe a y e a r later. D r . 0.: The R o c k e f e l l e r I n s t i t u t e c e r t a i n l y h a s made i t s mark i n many ways. I t ' s r a t h e r remarkable whey you look back a t t h i s p e r i o d a t t h e 69 people t h a t d i d work t h e r e a t one time i n d i f f e r e n t f i e ds. Quite a c o l l e c t i o n of s c i e n t i f i c t a l e n t . D r . V.: Yes, most of t h e s e n i o r men t h e r e were l e a d e r s i n t h e i r f i e l d s . And a v e r y l a r g e p r o p o r t i o n of the j u n i o r men t h e r e went o u t and became leaders. It w a s F l e x n e r ' s i d e a , when t h e I n s t i t u t e s t a r t e d , and which he t o l d me when I went down from Ann Arbor t o i n t e r v i e w him, t h a t young men would come t h e r e and work and g i v e t h e i r e n t h u s i a s m and energy and l e a r n from t h e o l d e r men and from the e x p e r i e n c e and go o u t a f t e r a longer o r s h o r t e r t i m e . And t h a t was c a r r i e d on. A f t e r I ' d been i n t h e I n s t i t u t e a b o u t three y e a r s , C a r l A l s b e r g , who w a s a t that time head of t h e Bureau of Chemistry i n Washington, o f f e r e d me t h e j o b of Assis- t a n t Chief which w a s r a t h e r a n u n u s u a l t h i n g f o r as young a chap a s I was. I was v e r y fond o f Carl Alsberg--knew him v e r y w e l l . I went t o F l e x n e r and t o l d him what t h e s i t u a t i o n w a s and I s a i d , "You t o l d m e when I came h e r e t h a t j u n i o r p o s i t i o n s were temporary and t h a t when good o p p o r t u n i t i e s came on i t w a s e x p e c t e d t h e young men would go o u t and s t a r t o t h e r t h i n g s and i t seems t o m e t h a t t h i s i s t h e t i m e f o r m e t o move on." He s a i d , "No, some o f o u r young men we want t o keep. I'd l i k e t o have you s t a y on.'' So, o t h e r w i s e I would have gone t o t h e Department of A g r i c u l t u r e , b u t t h a t ' s a t y p i c a l F l e x n e r d e c i s i o n . D r . 0.: Right. R i g h t , and brought o n by your a p p r o a c h i n g him r a t h e r than h i s i n i t i a t i n g it. D r . V.: Well, i t o n l y took him a minute t o make up h i s mind! If I ' d gone t o Washington, I p r o b a b l y , t o j u d g e from o t h e r p e o p l e , would have s t a y e d t h e r e a few y e a r s and t h e n t a k e n a t e c h n i c a l j o b i n some food 70 producing company, and been p r e t t y r i c h ! But F l e x n e r - - i t w a s a c r i t i c a l moment and i t d i d n ' t t a k e him a minute t o make up h i s mind what t o do. And t h a t w a s q u i t e a commitment t o make because i t was a commitment. D r . 0.: Yes. And from t h a t p o i n t on does one j u s t p r o g r e s s e s s e n t i a l l y i n stages? Dr. V.: It w a s y e a r s b e f o r e I became a f u l l member of t h e I n s t i t u t e . D r . 0.: There were a l i m i t e d number of f u l l members? D r . V.: There was never a d e f i n i t e number, b u t t h e number w a s l i m i t e d because each one meant p r a c t i c a l l y a department and t h e I n s t i t u t e o n l y had a c e r t a i n amount of room. No, I was i n no h u r r y t o move up, b u t i f I had t o move o u t e v e n t u a l l y , t h a t looked l i k e a good time and a chance t o go w i t h a man of whom I was v e r y fond. No, I w a s i n no h u r r y t o l e a v e Levene. I l o v e d working w i t h Levene. D r . 0.: Are t h e r e any o t h e r members of t h e R o c k e f e l l e r I n s t i t u t e o r H o s p i t a l we h a v e n ' t touched upon t o d a y t h a t you would c a r e t o make a s t a t e m e n t a b o u t o r comment a b o u t i n any way? Dr. V.: W e l l , t h e r e was A l f r e d Cohn, who w a s a c o l l e a g u e i n t h e H o s p i t a l a l l t h e time I was t h e r e . A profound s c h o l a r . Very s i n c e r e s c i e n t i s t . Good f r i e n d . Dr. 0.: And a b r o t h e r of E. J . ? V.: A b r o t h e r of Edwin, yes. 71 D r . 0.: Now, Edwin a l s o had s p e n t some t i m e , d i d he n o t , a t t h e Rockefeller? D r . V.: No, Edwin w a s never t h e r e . Dr. 0.: That's right. He and D r . H a s t i n g s were f i r s t t o g e t h e r a t Columbia. I g u e s s t h a t was i t . Dr. V.: Edwin grew up p r e t t y much under Henderson a t Harvard, and s t a y e d t h e r e and d i e d t h e r e . But A l f r e d knew e v e r y t h i n g t h a t t h e r e w a s known a b o u t t h e h e a r t and c i r c u l a t i o n . He w a s a g r e a t s c h o l a r , and some of t h e men t h a t worked w i t h him went o u t and became l e a d e r s i n c l i n i c a l work on t h e h e a r t . One o f them was Robert Levy who w a s on t h e f a c u l t y a t Columbia and w a s p r o b a b l y t h e l e a d i n g h e a r t s p e c i a l i s t i n New York. Another was Sam Levine. D r . 0.: I ' d f o r g o t t e n t h a t Sam Levine had s p e n t time t h e r e . Dr. V.: He j u s t d i e d t h i s p a s t y e a r i n Boston. He had a v e r y eminent p o s i t i o n i n Boston. D r . 0.: Oh yes. H i s s o n was a m e d i c a l s c h o o l c l a s s m a t e o f mine. D r . V.: Yes? D r . 0.: Yes. Herb L e v i n e , who i s now a c a r d i o l o g i s t h i m s e l f i n Boston. Dr. V.: I owed q u i t e a good d e a l t o a man t h a t had worked w i t h m e f o r a number of y e a r s . T h a t was Ed S t i l l m a n . He was a Hopkins g r a d u a t e who had come up a f t e r he f i n i s h e d h i s i n t e r n s h i p a t Hopkins, came up and 72 j o i n e d t h e s t a f f of t h e R o c k f e l l e r H o s p i t a l t h e same time t h a t I moved i n t o it. He was working w i t h A l l e n on t h e d i a b e t i c p a t i e n t s and t r y i n g t o do d e t e r m i n a t i o n s of o x y b u t y r i c a c i d i n u r i n e by t h e methods t h a t were a v a i l a b l e t h e n and t h e y w e r e n ' t good and he had a d e v i l o f a time. A l l e n was a c l i n i c i a n and c o u l d n ' t h e l p him any i n c h e m i s t r y , s o S t i l l - man and I more o r less teamed up t o overcome h i s problems and e v e n t u a l l y g o t working t o g e t h e r v e r y much. He took c h a r g e of p a t i e n t s whom we s t u d i e d w i t h r e g a r d t o t h e i r a c i d - b a s e b a l a n c e and metabolism. He w a s a natural-born physician. He w a s c o m p l e t e l y i n t e r e s t e d i n a p a t i e n t , and i n t h e whole p a t i e n t , and I r e a l l y l e a r n e d a l o t of i n t e r n a l medi- c i n e from S t i l l m a n . D r . 0.: Edward S t i l l m a n ? Dr. V.: Edward S t i l l m a n , yes. He j u s t d i e d a b o u t a y e a r ago. He e v e n t u a l l y went w i t h Palmer up t o P r e s b y t e r i a n H o s p i t a l and w a s on t h e f a c u l t y t h e r e on a p a r t t i m e b a s i s , and p a r t t i m e he p r a c t i c e d medicine-- s p e c i a l i z i n g p a r t i c u l a r l y i n m e t a b o l i c diseases. He w a s a man, t h e k i n d of d o c t o r t h a t would make a p a t i e n t t h i n k h e f e l t b e t t e r : One of o u r d i a b e t i c p a t i e n t s was a p h y s i c i a n from Boston, N a t h a n i e l Bowditch P o t t e r ; one o f t h e o l d Boston families. Bowditch, you know, is a n o l d Boston name. He w a s one of t h e l e a d i n g p h y s i c i a n s of Boston. Had e v e r y t h i n g behind him. I m p r e s s i v e , handsome f e l l o w . S i x f e e t t a l l , had a beard l i k e Mephistopheles: A t h o r o u g h l y good i n t e r n i s t . He'd been a p a t i e n t of J o s l i n and had been on t h e cream d i e t and been g e t t i n g worse and worse and f i n a l l y h e a r d a b o u t t h e I n s t i t u t e and he came and p u t h i m s e l f i n o u r hands and Ed t o o k c h a r g e o f him. He had a t o l e r a n c e of a b o u t 1600 73 calories. When h e g o t down t o t h a t he d i d n ' t p r o g r e s s and he d i d n ' t g e t i n t o t r o u b l e b u t he c o u l d n ' t t a k e more t h a n t h a t . He g o t i n good enough condition t o return t o l i f e . He w a s so much p l e a s e d w i t h t h e way t h e R o c k e f e l l e r H o s p i t a l went a t t h i n g s t h a t he g o t some money donated and s t a r t e d t h e Santa Barbara Cottage Hospital o u t i n Santa Barbara, Ca l i f o r n i a . Dr. 0.: Oh y e s , I'm f a m i l i a r w i t h t h a t i n s t i t u t i o n . I had no i d e a t h a t t h i s name was connected w i t h i t though. D r . V.: H e hoped t o do t h e same s o r t o f work and t r e a t m e n t t h a t we were doing a t t h e R o c k e f e l l e r . W e l l , once i n a w h i l e h e g o t low i n h i s mind. He had had TB and h e knew t h a t the l o w - c a l o r i e d i a b e t i c d i e t involved a t h r e a t from t h e TB, b u t i f h e d i d n ' t s t i c k t o the d i e t h i s d i a b e t e s would p r o g r e s s ( i t w a s b e f o r e i n s u l i n w a s a v a i l a b l e ) . When he r e a l l y g o t d i s c o u r a g e d h e ' d c a l l up Ed S t i l l m a n , o s t e n s i b l y t o a s k him a b o u t some p e r f e c t l y t r i v i a l t h i n g i n h i s m e d i c a t i o n o r t r e a t m e n t t h a t he knew j u s t as w e l l a s Ed d i d , b u t r e a l l y j u s t t o h e a r E d ' s v o i c e o v e r t h e telephone D r . 0.: T h a t ' s remarkable. D r . V.: Ed makes m e t h i n k of a n o l d d o c t o r t h a t I met on a b o a t a c r o s s t h e P a c i f i c once. He s a i d , " R e a l l y , t h e c h i e f e s s e n t i a l o f a d o c t o r i s t h a t t h e p a t i e n t w i l l do t h i n g s t o p l e a s e h i s d o c t o r t h a t h e w o n ' t do t o s a v e h i s own l i f e : " D r . 0.: I t ' s v e r y i n t e r e s t i n g , t h i s , I ' m s u r e , comes i n n o t i n f r e q u e n t l y i n t h e care of p a t i e n t s ; somebody who c a n e s t a b l i s h t h e kind of r a p p o r t t h a t t h e p a t i e n t f e e l s t h i s way. 74 Dr. V.: Well, S t i l l m a n was a real doctor. S t a d i e was a n o t h e r charac- t e r t h a t was a g r e a t f e l l o w . I t o l d you what a j o b he d i d on t h e oxygen chamber. D r . 0.: Yes. D r . V.: He f i n i s h e d i t and it was a complete j o b . Then h e went on t o o t h e r t h i n g s , and o t h e r p e o p l e t o o k i t up where he l e f t o f f . I was sur- p r i s e d t o f i n d , and somewhat shocked, twenty y e a r s l a t e r , t h e young d o c t o r s t h a t were u s i n g t h a t oxygen chamber r i g h t t h e r e i n t h e R o c k e f e l l e r H o s p i t a l d i d n ' t know t h a t S t a d i e had s t a r t e d it! He e v e n t u a l l y went t o t h e U n i v e r s i t y o f P e n n s y l v a n i a a s a Research P r o f e s s o r and d i d a g r e a t d e a l o f work on c a r b o h y d r a t e metabolism, a n d , d u r i n g t h e w a r , on t h e e f f e c t s of h i g h oxygen t e n s i o n which became i m p o r t a n t w i t h r e g a r d t o divers. There was a g r e a t p u z z l e t o f i n d o u t why i t i s t h a t h i g h oxygen t e n s i o n c a u s e s c o n v u l s i o n s and is t o x i c i n o t h e r ways. Stadie did a b e a u t i f u l j o b i n t e s t i n g a l l t h e enzymes i n t h e nervous s y s t e m t h a t you could t h i n k of and t h e e f f e c t of oxygen on them, b u t nobody y e t h a s g o t t h e answer. J. B. S. Haldane worked on i t , t o o . He w a s t h e s o n of t h e John S c o t t Haldane I spoke o f . They were a g r e a t f a m i l y . L o r d Haldane w a s John Scott's brother. Both Jack and h i s f a t h e r d i d n ' t h e s i t a t e t o u s e them- s e l v e s as e x p e r i m e n t a l a n i m a l s . J a c k , who was a b i g powerful f e l l o w , p u t h i m s e l f under h i g h oxygen t e n s i o n and had a c o n v u l s i o n which c r u s h e d a vertebra. He r e c o v e r e d from i t so t h a t a l l i t l e f t him w i t h , so f a r a s I know, was a s t i f f back. There's a story--1 think i t ' s printed 76 p o s s i b l y some of the Danes (though my immediate i m p r e s s i o n i s t h a t t h e y came a l o n g a b i t l a t e r ) who were working i n t h i s g e n e r a l a r e a ? Dr. V.: Well, t h e Danes had worked i n i t , t h e r e w a s H a s s e l b a l c h , and Lundsgaard had worked w i t h H a s s e l b a l c h , a n d , a f t e r H a s s e l b a l c h , E r i k Warburg. Haldane--J. S . Haldane--did a b e a u t i f u l p i e c e of work i n showing t h a t i f you have reduced blood w i t h a c e r t a i n C02 t e n s i o n and you r u n oxygen i n t o i t w i t h o u t changing t h e C02 t e n s i o n , you push some of t h e C 0 2 o u t of t h e blood. T h a t i s , as H a s t i n g s and I showed, t h e oxygenated hemoglobin i s more a c i d t h a n reduced hemoglobin so t h a t oxy- g e n a t i n g blood i s l i k e a c i d i f y i n g i t . T h a t ' s known as t h e Haldane e f f e c t , and i t ' s v e r y i m p o r t a n t . With r e g a r d t o t h e a c i d - b a s e q u e s t i o n , new t e c h n i q u e s have been worked o u t f o r m i c r o d e t e r m i n a t i o n s of C02 t e n s i o n and pH i n the b l o o d , b u t t h e c o n c e p t i o n s of r e s p i r a t o r y a l k a l o s i s and a c i d o s i s and t h e m e t a b o l i c a c i d o s i s and a l k a l o s i s - - s u c h a s you have i n d i a b e t e s - - t h e y a r e p r a c t i - c a l l y t h e same as t h e y were when we worked on them a t t h e R o c k e f e l l e r . A s t r u p , i n Copenhagen, worked o u t a b e a u t i f u l l i t t l e a p p a r a t u s where w i t h a few d r o p s of blood you g e t C 0 2 t e n s i o n and pH. I n t e r e s t i n g how h e came t o do t h a t . He t o l d m e a b o u t i t . They had a n epidemic of p o l i o - myelitis. There were a l o t of c h i l d r e n t h a t g o t r e s p i r a t o r y p a r a l y s i s so t h e y had t o be k e p t a l i v e by a r t i f i c i a l r e s p i r a t i o n . And i t was i m - p o r t a n t t o g i v e them j u s t enough r e s p i r a t i o n t o keep t h e C 0 2 t e n s i o n and t h e blood pH w i t h i n normal range. You c o u l d overdo it and g i v e them respiratory alkalosis. Using my f u l l - s i z e d 50 m l . manometric machine which w a s what t h e y had t h e n , i t t o o k t o o much blood t o do r e p e a t e d 77 d e t e r m i n a t i o n s ; t h e y needed something you c o u l d do w i t h a few d r o p s of blood. For t h a t r e a s o n A s t r u p worked o u t h i s m i c r o machine which i s v e r y much used a l l around t h e w o r l d now. D r . 0.: Yes. We had one i n c l i n i c a l p a t h o l o g y a t N I H I know. Well t h e Danes, i f you c a n make g e n e r a l i z a t i o n s l i k e t h i s , c e r t a i n l y seem t o be q u i t e t a l e n t e d a l o n g t h e l i n e s o f d e v e l o p i n g t e c h n i q u e s s u c h a s t h i s , micromethods. Dr. V.: Yes, t h e Danes have provided more t h a n t h e i r s h a r e of good scientists. Linderstrdm-Lang developed a whole t e c h n i q u e of u l t r a m i c r o - chemistry. And I t h i n k p r e t t y n e a r 100 Americans have gone t h r o u g h Linderstrdm-Lang's hands and come back and t a k e n u s u a l l y i m p o r t a n t p o s i - tions. H a s t i n g s worked w i t h him f o r awhile. D r . 0.: Yes. Lowry----- Dr. V.: Lowry and Anfinsen. Linderstrdm-Lang was a d e l i g h t f u l person. I landed i n Copenhagen one time twenty y e a r s ago and c a l l e d him up and he s a i d , "1'11 be r i g h t o v e r " and h e came o v e r t o t h e h o t e l where we were s t a y i n g and he had t h e o l d e s t l o o k i n g Ford j a l o p y t h a t you e v e r saw i n your l i f e : Nobody would buy it f o r a secondhand c a r h e r e , b u t we had a w o n d e r f u l time. He n o t o n l y was a n e l e g a n t c h e m i s t b u t h e a l s o w a s a m u s i c i a n and he p a i n t e d v e r y w e l l , and he was l i k e l y t o b e t h e l i f e of any p a r t y t h a t he w a s i n . H i s a i m w a s t o be a b l e t o f o l l o w what went on i n a s i n g l e c e l l and he worked o u t t h e s e u l t r a m i c r o m e t h o d s toward t h a t . He d i d e x c e l l e n t work 78 on chemical r e a c t i o n s , b u t he developed a whole m i c r o t e c h n i q u e t h a t i s used t h e world around. H e and N i e l s Bohr were t h e two g r e a t l i g h t s i n Copenhagen f o r many y e a r s . Now t h e y ' r e b o t h gone. Copenhagen i s n o t t h e same town anymore. There a r e o t h e r outstanding s c i e n t i s t s t h e r e , b u t i t would be h a r d t o r e p l a c e t h o s e two. D r . 0.: Yes. C r a a f o r d , t h e s u r g e o n , is i n Copenhagen, i s n ' t h e ? Isn't he a Dane? D r . V.: Who? Dr. 0.: C-r-a-a-f-o-r-d? Dr. V. : I d o n ' t happen t o know him. I d i d n ' t g e t t o know t h e s u r g e o n s i n Denmark. I was t h e r e once and I dropped i n , a s u s u a l , t o s e e Linderstrdm-Lang and h e t o l d me a b o u t t h e l a t e s t work t h e y were doing and I t o l d him what we were d o i n g h e r e a t Brookhaven, and h e s a i d , "We have a l i t t l e meeting a f t e r l u n c h once a week. Would you d r o p i n and t e l l the s t a f f a b o u t t h i s work tomorrow?" I said, "All right." We had worked o u t q u i t e a l o t a b o u t t h e s t r u c t u r e of t h e amino a c i d h y d r o x y l y s i n e t h a t we d i s - c o v e r e d , and how i t was formed by h y d r o x y l a t i o n of l y s i n e , and something about i t s function i n collagen. He s a i d , 'vi11 you d r o p i n tomorrow a f t e r n o o n and t e l l t h e s t a f f a b o u t i t ? " So I dropped i n t h e n e x t a f t e r - noon and i n s t e a d o f h a l f a dozen young f e l l o w s he had a hundred p e o p l e t h e r e and h a l f a dozen f u l l p r o f e s s o r s i n t h e f r o n t row: I pretty n e a r went t h r o u g h t h e f l o o r because I was n o t p r e p a r e d f o r such a n audience. 79 D r . 0.: Oh my, i t w a s n ' t e x a c t l y what you were e x p e c t i n g ! Dr. V.: I h a d n ' t p r e p a r e d a formal t a l k . It was t o o bad t h a t Linderstrdm-Lang c o u l d n o t go on l i v i n g . There re o t h e r good men i n t h e C a r l s b e r g l a b o r a t o r i e s s t i l l b u t t h e y ' r e n o t Linderstrdm-Langl [ pause1 D r . 0.: The d a t e i s May 28, 1969. We're a g a i n i n t h e o f f i c e of D r . Van S l y k e a t Brookhaven N a t i o n a l L a b o r a t o r i e s . P r i o r t o beginning a d i s c u s s i o n of D r . Van S l y k e ' s c a r e e r a t Brookhaven, h e ' s g o i n g t o com- ment a b o u t D r . W i l l i a m M a n s f i e l d C l a r k . Dr. V.: I f i r s t m e t C l a r k a t Woods Hole. We were b o t h t h e r e as a s s i s - t a n t s t o D r . C a r l A l s b e r g who w a s i n c h a r g e o f t h e L a b o r a t o r y of Bio- c h e m i s t r y a t t h e F i s h C o m i s s i o n L a b o r a t o r y i n Woods Hole. We had a v e r y good time t o g e t h e r and s p e n t t h e summer t h e r e ; t h a t w a s i n t h e summer of 1908. The summer of 1909, I went t o Woods Hole and developed t y p h o i d f e v e r s o I l o s t t h e f i r s t p a r t of t h a t summer! D r . 0.: Was t h i s a l a b o r a t o r y i n f e c t i o n ? Dr. V.: No, i t w a s a n i n f e c t i o n t h a t came from a c a r r i e r i n a d a i r y h e r d on Long I s l a n d and t h i s d a i r y provided m i l k f o r t h e p a r t of New York r i g h t around t h e R o c k e f e l l e r I n s t i t u t e , and I presume t h a t I picked i t up a t a r e s t a u r a n t t h e r e . There w e r e , I t h i n k , a b o u t 80 c a s e s from t h a t one d a i r y . But I went back t o Woods Hole f o r t h e summer i n 1910. A l s b e r g had gone t o Washington t o become Chief of t h e Bureau of Chemistry 80 a t t h a t time and so I succeeded t o h i s p l a c e i n c h a r g e of t h e l a b o r a - t o r y , and C l a r k , who was one y e a r my j u n i o r , became my a s s i s t a n t . There was no d i f f e r e n c e between u s i n a c t u a l e x p e r i e n c e o r r e s p o n s i b i l i t y f o r t h e work, and we had a marvelous summer t h e r e t o g e t h e r . D r . 0.: He c e r t a i n l y had a v e r y r i c h s e n s e o f humor. D r . V.: Yes, he had a g r e a t s e n s e o f humor. W e used t o work u n t i l 1 2 o ' c l o c k e v e r y morning. We were working on t h e metabolism of meat compared w i t h f i s h , g i v i n g a meal t o a dog e v e r y morning a t 8 o ' c l o c k and c a t h e t e r i z i n g h e r a t 4-hour i n t e r v a l s . After t h e 12 o'clock cathe- t e r i z a t i o n C l a r k and I would go f o r a swim and we'd t a k e a n i c e l o n g swim. The l a s t hundred y a r d s back we'd s w i m h a r d , and C l a r k always b e a t me by t e n y a r d s : H e w a s a good swimmer. N i n e t e e n t e n was t h e l a s t y e a r t h a t I went t o Woods Hole b e c a u s e i n 1 9 1 1 I went abroad and worked w i t h E m i l F i s c h e r and I n e v e r g o t back t o Woods Hole L a b o r a t o r y a g a i n , b u t C l a r k and I always remained i n t i m a t e f r i e n d s , a l t h o u g h we o n l y o c c a s i o n a l l y would meet a t my home o r h i s , o r a t m e e t i n g s , b u t we always f e l t a s though we belonged t o t h e same f r a - ternity: D r . 0.: H i s "Hydrogen Ions" became a c l a s s i c i n t h e f i e l d . Dr. V.: Yes Dr. 0.: We1 ,I c a n s t i l l remember, a s a m e d i c a l s t u d e n t , measuring t h e p H ' s of a v a r i e t y of t h i n g s u s i n g t h e o l d c o l o r i m e t r i c methods. 81 D r . V.: Yes. We d i d n ' t have t h e photometers t h e n . D r . 0.: Right, r i g h t . That's true. D r . V.: The two men t h a t p u t pH o n t h e map were Sorensen, 1 Denmark, and C l a r k i n t h e United S t a t e s . D r . 0.: Again, i n a s e n s e , C l a r k ' s work, a s your work i n e l e c t r o l y t e b a l a n c e and blood g a s s e s , f i l l e d a v o i d , r e a l l y . It was a n a r e a o f application n c l i n i c a l medicine which h a s opened up t o t a l l y new avenues. Dr. v.: Yes C l a r k ' s work w a s a g r e a t c o n t r i b u t i o n . [End of S i d e 11, Reel 21 [ S i d e I , R e e l 31 Recorded May 28, 1969. D r . 0.: You had mentioned y e s t e r d a y t h a t i t w a s 1949 t h a t you l e f t t h e Rockefeller, i s t h a t correct? D r . V.: W e l l , I r e a c h e d t h e r e t i r i n g age i n 1948. From J u l y 1, 1948 ' t i l J u l y 1, 1949, I d i v i d e d my time between t h e R o c k e f e l l e r and Brook- haven. I s p e n t a b o u t h a l f of t h e t i m e a t t h e R o c k e f e l l e r f i n i s h i n g up work t h a t I had going t h e r e , and h a l f t h e time o u t h e r e a t Brookhaven g e t t i n g t h e m e d i c a l and b i o l o g y d e p a r t m e n t s o r g a n i z e d . Then i n t h e f a l l o f ' 4 9 , I moved o u t t o Long I s l a n d and s p e n t f u l l time a t Brookhaven from t h e n on. Dr. 0.: Am I c o r r e c t t h a t t h e o r i g i n a l thought behind t h e e s t a b l i s h m e n t o f t h e Brookhaven N a t i o n a l L a b o r a t o r y was to. make a v a i l a b l e t o u n i v e r - s i t i e s equipment which would be i m p r a c t i c a l f o r e a c h t o o b t a i n . 82 D r . V. : T h a t was t h e i d e a behind i t , yes. D r . 0.: So t h e a s s o c i a t e d u n i v e r s i t i e s became a n i n c o r p o r a t e d group. I s i t f i v e o r n i n e - - 1 c a n ' t remember t h e f i g u r e - - u n i v e r s i t i e s i n v o l v e d i n the a s s o c i a t e d u n i v e r s i t i e s . D r . V. : T h e r e were n i n e . D r . 0.: Nine. With t h e i d e a o f h a v i n g one c e n t r a l f a c i l i t y which t h e y would t h e n share each----- Dr. v.: Yes. D r . 0.: -----and c o n t r i b u t e t o t h e s u p p o r t t h e r e o f , and so on. My i m p r e s s i o n i s , and I t h i n k p o s s i b l y on some of my c o n v e r s a t i o n s w i t h D r . H a s t i n g s , t h a t e a r l y on i n t h e p l a n n i n g of t h i s t h e r e was some con- c e r n among p e o p l e l i k e D r . H a s t i n g s t h a t t h e r e was a move on, o r a t l e a s t i n i t i a l l y t h e t r e n d seemingly was toward l i m i t i n g t h i s f a c i l i t y t o t h e p h y s i c a l s c i e n c e s and n o t i n c l u d i n g medicine. Am I c o r r e c t i n t h s assumption? Dr V.: I was n o t i n on t h e e a r l y p l a n n i n g . I t h i n k the Associated Un v e r s i t i e s , I n c o r p o r a t e d was o r g a n i z e d i n ' 4 7 and t h e - - o r maybe a l i t t l e b e f o r e t h a t - - b u t i n '48, when I was f i r s t i n c o n t a c t h e r e , t h e l a b o r a t o r y w a s a l r e a d y going. D r . 0.: I see. Dr. V.: P h i l l i p Morse, t h e p h y s i c i s t a t Harvard, w a s t h e f i r s t D i r e c t o r . 83 H e was D i r e c t o r then. H e d i d n ' t l i k e a d m i n i s t r a t i v e work and r a t h e r soon he went back t o H a r v a r d and Hayworth t o o k h i s p l a c e . D r . 0.: Hayworth? Dr. V.: Hayworth, yes. Leland Hayworth. The i d e a of h a v i n g a l a b o r a - t o r y a t Brookhaven w a s g e n e r a t e d by p h y s i c i s t s and I imagine t h a t y o u ' r e p r o b a b l y c o r r e c t i n t h a t t h e y d i d n ' t t h i n k of h a v i n g t h e l i f e s c i e n c e s as p a r t of i t a t f i r s t , I d o n ' t know how t h e i d e a of t h e l i f e s c i e n c e s came i n t o i t . H a s t i n g s was one of t h e f i r s t t r u s t e e s . There were two t r u s t e e s from each of t h e s e n i n e u n i v e r s i t i e s . The i d e a was t o have one of t h e two who w a s a s c i e n t i s t and t h e o t h e r one who would be the a d m i n i s t r a t o r and t h a t worked o u t p r e t t y w e l l . W e l l , H a s t i n g s w a s a s c i e n t i s t from Harvard and I presume h e w a s one o f t h e f i r s t t r u s t e e s because h e was a t r u s t e e when I was approached v e r y e a r l y i n 1948--the w i n t e r of 1948, a s a matter of f a c t . H a s t i n g s t a l k e d t o m e f i r s t a b o u t i t , t h e n Morse came i n t o New York and t a l k e d t o me a b o u t i t and t h e n Shoup. A t the s t a r t of Brookhaven t h e o r g a n i z a t i o n had two men t h a t s h a r e d r e s p o n s i - b i l i t i e s , Shoup and Morse. I ' v e f o r g o t t e n e x a c t l y what Shoup's d e s i g n a - t i o n was b u t h e e v e n t u a l l y dropped o u t and was n o t r e p l a c e d . I think i t ' s always a m i s t a k e t o have two h e a d s t o a n o r g a n i z a t i o n . D r . 0.: A c t u a l l y , you came on t h e n when Hayworth w a s h e r e o r w a s Morse here----- Dr. V.: Morse was s t i l l on when I came o n p a r t time i n J u l y '48. When I came on f u l l time i n ' 4 9 , Hayworth w a s D i r e c t o r . 84 D r . 0.: You came on w i t h t h e t i t l e of A s s i s t a n t D i r e c t o r w i t h t h e r e s p o n s i b i l i t y f o r t h e d e p a r t m e n t s o f medicine and b i o l o g y . Dr. V.: Yes. I w o u l d n ' t be s u r p r i s e d i f H a s t i n g s w a s r e s p o n s i b l e f o r medicine and b i o l o g y b e i n g p a r t o f t h e p l a n . The i d e a of a Brookhaven, I think, definitely did originate with the physicists. There were o t h e r a t o m i c energy l a b o r a t o r i e s a t Oak Ridge and Argonne and Hanford, b u t i n t h e n o r t h e a s t of t h e c o u n t r y where t h e r e w a s t h e g r e a t e s t c o n c e n t r a t i o n of s c i e n t i s t s , t h e r e was none. Dr. 0.: And t h e f a c i l i t y , o r i g i n a l l y , was l i t e r a l l y u s i n g t h e b u i l d i n g s l e f t o v e r from Camp Yaphank which w a s r a t h e r r u s t i c I ' m s u r e f o r a period. D r . V.: Yes. They s e r v e d p r e t t y w e l l . D r . 0.: Some of them, I g a t h e r , a r e s t i l l s t a n d ng o v e r t h e r e by t h e apartments. Some of t h e s e l o n g bungalow-type t h ngs on s t i l t s t h a t you described a r e s t i l l there. D r . V.: Yes. Some of them were t u r n e d i n t o a p a r t m e n t s and t h e y were modernized so t h e y made v e r y c o m f o r t a b l e a p a r t m e n t s . The o r i g i n a l medi- c a l department was i n what w a s t h e o l d Army H o s p i t a l . D r . 0.: I see. Then t h a t h a s s u b s e q u e n t l y been t o r n down. This build- i n g I g a t h e r came---- D r . V.: T h a t ' s a l l gone now. It was a b o u t a m i l e and a h a l f from h e r e . I t w a s o v e r i n t h e a r e a where t h e a p a r t m e n t s a r e , not very f a r from where you s p e n t t h e n i g h t . 85 Dr. 0.: Well, you s t a r t e d o f f w i t h t h e i d e a of h a v i n g a number of c l i n i c a l beds t o be u s e d by t h e i n v e s t i g a t i n g group h e r e a t Brookhaven. D r . V.: Yes. D r . 0.: Are t h e d i v i s i o n s now w i t h i n t h e m e d i c a l group e s s e n t i a l l y what t h e y were a t t h a t t i m e ? D r . V. : They grew up as we g o t men h e r e . When I came o u t h e r e i n '48 D r . Robert Love, who i s s t i l l h e r e , and a n a s s i s t a n t p h y s i c i a n , who d i d p h y s i c a l e x a m i n a t i o n s and t o o k c a r e o f m e d i c a l e m e r g e n c i e s , were t h e o n l y d o c t o r s i n t h e m e d i c a l department. Soon i n 1948 a f t e r I j o i n e d t h e l a b o r a t o r y on p a r t t i m e I g o t Lee F a r r t o do l i k e w i s e and t o g e t h e r we r e c r u i t e d o t h e r men around whom r e s e a r c h g r o u p s , which became c a l l e d " D i v i s i o n s " developed. F a r r and I came h e r e t o g e t h e r on f u l l t i m e i n 1949. The o r g a n i z a t i o n , you might s a y , grew l i k e Topsy r a t h e r t h a n being de- s i g n e d from t h e s t a r t . D r . 0.: B u i l t around t h e men. D r . V.: It w a s b u i l t around t h e men. D r . 0.: The c l i n i c a l beds you have h e r e a r e p r i m a r i l y used f o r p a t i e n t s w i t h m a l i g n a n c i e s t h a t a r e r e c e i v i n g v a r i o u s s o r t s of r a d i o t h e r a p y o r nuclear therapy? D r . V.: We have 48 beds and t h e y ' r e p r i m a r i l y f o r p a t i e n t s t h a t a r e being i n v e s t i g a t e d . I f t h e r e i s a n emergency c a s e - - a c c i d e n t , for example, on t h e s i t e - - b e d s c a n be used t e m p o r a r i l y t o c a r e f o r i t , b u t 86 t h e i r real use i s f o r p a t i e n t s t h a t a r e being i n v e s t i g a t e d f o r t h e c l i n i c a l c o n d i t i o n s t h a t t h e y have. D r . 0.: I b e l i e v e you mentioned y e s t e r d a y , you a c t u a l l y were even i n i t i a l l y d i v i d i n g y o u r time between a d m i n i s t r a t i o n and y o u r own l a b - o r a t o r y work. How l o n g d i d you s t a y i n t h i s p o s i t i o n as A s s i s t a n t D i r e c t o r f o r Medicine and B i o l o g y ? D r . V.: I stayed i n it f o r three years. By t h a t time I had g o t t e n F a r r f o r Head of Medicine and C u r t i s f o r Head o f Biology and t h e d e p a r t m e n t s were well-founded and g o i n g and I c o n s i d e r e d t h a t i t w a s n ' t n e c e s s a r y t o have a n a d m i n i s t r a t o r s t a n d i n g between t h e heads of t h e s e d e p a r t - ments and Hayworth. I t h o u g h t i t was b e t t e r t o have F a r r and C u r t i s r e p o r t d i r e c t t o Hayworth. B e s i d e s which, I l i k e d t h e l a b o r a t o r y work more t h a n a d m i n i s t r a t i o n ! But w e had a good s t a r t . We'd g o t t e n what I c o n s i d e r t o p g r a d e men t o s t a r t , and i f you s t a r t w i t h t o p g r a d e men you c a n keep i t up; you s e t your s t a n d a r d . D r . 0.: Are D r . F a r r and C u r t i s s t i l l a t Brookhaven? Dr. V.: No, F a r r i n 1961 a c c e p t e d a c a l l from A u s t i n , Texas t o o r g a n i z e a s o r t of "Brookhaven Medical Department" down t h e r e , and s o he l e f t and Bond, who w a s one of t h e men t h a t he g o t who i s b o t h a Ph.D. and a n M.D., w a s made Head of t h e Department. Bond had i t f o r a b o u t f i v e y e a r s and by t h a t time Medicine and Biology had grown a good d e a l and t h e D i r e c t o r , Goldhaber, f e l t t h a t h e wanted t o have a n A s s i s t a n t D i r e c t o r t h a t c o u l d f u n c t i o n t h e way I d i d , t o a d v i s e him. So he s t o l e Bond away from t h e Medical Department t o be A s s o c i a t e D i r e c t o r and D r . Eugene 87 C r o n k h i t e a c c e p t e d t h e Chairmanship of t h e Medical Department. In F a r r , Bond and C r o n k h i t e we've had t h r e e v e r y s u p e r i o r men f o r h e a d s o f Medi- cine. We've been v e r y f o r t u n a t e t o h a v e b e e n a b l e t o h o l d Bond and C r o n k h i t e as l o n g a s we now have. D r . 0.: When you r e t u r n e d t o t h e l a b o r a t o r y , f u l l t i m e , o r I should s a y r e a l l y , when you came t o Brookhaven i n i t i a l l y because even t h e n you had begun o r c o n t i n u e d working i n t h e l a b o r a t o r y p a r t t i m e , what a r e a s of r e s e a r c h d i d you c o n c e n t r a t e upon? Was there a change i n d i r e c t i o n from work you'd been d o i n g a t t h e R o c k e f e l l e r I n s t i t u t e ? D r . V.: Yes, q u i t e . I ' d been working on t h e k i d n e y a t t h e R o c k e f e l l e r Institute. One of t h e t h i n g s t h a t w a s needed i n i s o t o p e work, I remem- b e r H a s t i n g s s a i d when we f i r s t t a l k e d , was a n a c c u r a t e and s e n s i t i v e method f o r carbon 14. And I s p e n t a c o u p l e o f y e a r s working such a method o u t a t Brookhaven w i t h t h e h e l p o f Robert S t e e l e and John P l a z i n . Organic s u b s t a n c e s were burned i n two m i n u t e s w i t h a combustion m i x t u r e of chromic and i o d i c a c i d s . Then t h e CO2 was t r a n s f e r r e d t o a l k a l i i n t h e chamber of t h e manometric blood g a s a p p a r a t u s and C 0 2 w a s d e t e r - mined t h e same way you do a blood C 0 2 . F i n a l l y t h e chamber w a s connected up w i t h a g a s - c o u n t i n g chamber, and t h e C 0 2 w a s t r a n s f e r r e d t o t h a t and counted. T h a t method i s s t i l l a good d e a l used h e r e i n t h i s l a b o r a t o r y ; I d o n ' t know how much i n o t h e r s , b u t somewhat. T h a t was q u i t e a change from s t u d i e s of n e p h r i t i s . Then I a l s o d i d some o t h e r work on methods and s t a r t e d work on t h e b i o l o g i c a l s y n t h e s i s of c o l l a g e n . The way I g o t i n t o t h a t problem w a s t h a t w h i l e working i n t h e R o c k e f e l l e r I n s t i - t u t e , A l m a H i l l e r and I d i s c o v e r e d a h i t h e r t o unknown amino a c i d , 88 h y d r o x y l y s i n e , i n c o l l a g e n , and I w a s c u r i o u s as t o how i t w a s formed, w h e t h e r i t was c o m p l e t e l y s y n t h e s i z e d i n t h e body o r w h e t h e r i t w a s formed by a d d i n g oxygen t o l y s i n e . I had a n a s s i s t a n t , S i n e x , who came t o me from H a s t i n g s ' l a b o r a t o r y , and we worked on t h a t and we found t h a t t h e body c o u l d n o t make t h e h y d r o x y l y s i n e , o r d i d not make i t from any- thing except lysine. I f w e gave c a r b o n 14 l a b e l e d l y s i n e t o a r a t , we g o t c a r b o n 14 l a b e l e d h y d r o x y l y s i n e i n c o r p o r a t e d i n t o t h e c o l l a g e n , w i t h t h e same a c t i v i t y a s t h e l y s i n e t h a t was a l s o i n c o r p o r a t e d i n t o t h e c o l - lagen. And f u r t h e r m o r e , i f we gave t h e r a t h y d r o x y l y s i n e he c o u l d n ' t put i n t o the collagen----- D r . 0.: I n o t h e r words, h e c o u l d n o t c o n v e r t h y d r o x y l y s i n e t o c o l l a g e n . Dr. V.: He c o u l d n ' t u s e ready-made h y d r o x y l y s i n e . I f it w a s a l r e a d y made f o r him he c o u l d n ' t u s e i t ; he had t o make i t h i m s e l f o u t of l y s i n e i n o r d e r t o u s e it. It was a l s o shown i n work w i t h Edwin Popenoe t h a t t h e h y d r o x y l a t i o n of l y s i n e o c c u r r e d a t t h e moment of s y n t h e s i s of t h e collagen. It w a s n o t a t h i n g t h a t went o n f o r h o u r s o r days a f t e r t h e c o l l a g e n w a s b u i l t , b u t h y d r o x y l a t i o n of p a r t of t h e l y s i n e o c c u r r e d d u r i n g t h e p u t t i n g t o g e t h e r of t h e amino a c i d s t o make t h e c o l l a g e n . Then t h e q u e s t i o n a r o s e as t o t h e o r g a n i c c h e m i s t r y of t h e h y d r o x y l a t i o n . T h a t i s , t h e r e a r e s e v e r a l ways which you c a n p u t a n oxygen i n t o a CH2 t o make a CHOH. One p r o c e d u r e t h a t ' s used i n l i v i n g organisms a good d e a l i s t a k e away two hydrogens and form a double bond between two c a r - bons. From a w a t e r molecule you p u t hydroxyl o n one c a r b o n and hydro- gen on t h e o t h e r . T h a t ' s known t o o c c u r i n some b i o l o g i c a l r e a c t i o n s . We r a t h e r s u s p e c t e d it would be t h a t . But t h a t procedure would d i s p l a c e two hydrogens from two a d j a c e n t c a r b o n s on t h e 6-carbon l y s i n e c h a i n . T h a t d i d not happen. There w a s o n l y one hydrogen d i s p l a c e d , and t h a t was from c a r b o n 5, n e x t t o t e r m i n a l c a r b o n 6 , which c a r r i e s t h e NH2 group. It w a s e v e n t u a l l y found by s t u d y i n g t h e r e a c t i o n w i t h i s o t o p e s t h a t a n oxygen atom i s t a k e n on d i r e c t l y t o c a r b o n 5 of l y s i n e and changes t h e CH2 group t o CH(OH), t h e r e b y changing l y s i n e t o h y d r o x y l y s i n e . I n the meantime a group o f i n v e s t i g a t o r s i n Bethesda had been working on t h e h y d r o x y l a t i o n of p r o l i n e i n t h e body t o form h y d r o x y p r o l i n e . The mecha- nism seems v e r y s i m i l a r t o t h e h y d r o x y l a t i o n of l y s i n e , b u t t h e r e i s one d i f f e r e n c e t h a t h a s n o t been s o l v e d y e t . When p r o l i n e w i t h a t r i t i u m atom on c a r b o n 4 i s h y d r o x y l a t e d t h e t r i t i u m i s c o n v e r t e d i n t o t r i t i a t e d w a t e r , THO. The enzymic a c t i o n by which t h e h y d r o x y l a t i o n i s accom- p l i s h e d c a n be followed by measuring t h e t r i t i u m t h a t i s c o n v e r t e d i n t o THO. But i n t h e h y d r o x y l a t i o n of l y s i n e , a l t h o u g h t r i t i u m a t t a c h e d t o carbon-5 d i s a p p e a r s from t h e h y d r o x y l y s i n e , i t does n o t r e a p p e a r as THO. W e can't find it i n the water. T h a t i s one of t h e p o i n t s we s t i l l have t o work on. Another i s t o p u r i f y and c h a r a c t e r i z e t h e enxyme t h a t does t h e h y d r o x y l a t i o n of l y s i n e . Popenoe and Aronson a r e working on t h i s problem. D r . 0.: Have a l l of your s t u d i e s , i n g e n e r a l , been around c o l l a g e n f o r - mation i n r e c e n t y e a r s ? D r . V.: I have done, a s you might s a y , on t h e s i d e , work i n d e v i s i n g s e v e r a l methods, f o r c a l c i u m , l i p i d s , and pH i n plasma, f o r g a s o m e t r i c n i t r a t e d e t e r m i n a t i o n , a n d , w i t h Aronson a method f o r measuring C 0 2 i n my g a s machine and t h e n t r a n s f e r r i n g i t t o a s c i n t i l l a t i o n v i a l f o r 90 c o u n t i n g of carbon-14. But one might s a y t h a t t h e main e f f o r t o f t h e l a b o r a t o r y h a s been on t h e s i d e of c o l l a g e n . Another problem c o n c e r n i n g b o t h c o l l a g e n and h y d r o x y l y s i n e h a s been t h e i r reaction with periodate. The end o f t h e h y d r o x y l y s i n e molecule h a s , on c a r b o n s 5 and 6, t h e s t r u c t u r e -CH(OH).CHNH2. When 2 a d j a c e n t c a r b o n s have one of them a n amino group and t h e o t h e r a h y d r o x y l , t h e t o t a l group c a n r e a c t w i t h p e r i o d a t e , s p l i t t i n g o f f t h e end c a r b o n as formaldehyde and t h e amino group a s ammonia. I f , however, t h e amino group i s bound, as by a c e t y l a t i o n , o r t h e hydroxyl group i s bound, as by e s t e r i f i c a t i o n , p e r i o d a t e does n o t a t t a c k t h e s t r u c t u r e . The t e r m i n a l group i n h y d r o x y l y s i n e r e a c t s w i t h p e r i o d a t e c o m p l e t e l y and w i t h i n a minute. When t h e p e r i o d a t e r e a c t i o n i s a p p l i e d t o c o l l a g e n , however, t h e end groups of o n l y p a r t of t h e h y d r o x y l y s i n e r e a c t i n t h i s manner. If , after t h e r e a c t i o n of c o l l a g e n w i t h p e r i o d a t e t h e c o l l a g e n i s hydro- l y z e d , we g e t back 50 t o 90 p e r c e n t of t h e h y d r o x y l y s i n e , depending on what k i n d o f c o l l a g e n i t i s . Only 1 0 t o 50 p e r c e n t i s d e s t r o y e d by periodate. It v a r i e s - - y o u have a c i d - s o l u b l e , s a l t - s o l u b l e and i n s o l u b l e c o l l a g e n s , and c o l l a g e n s from d i f f e r e n t a n i m a l s . The n o n - r e a c t i o n of p a r t of t h e h y d r o x y l y s i n e i n t h e c o l l a g e n s w a s a p u z z l e . Was t h e p r o t e i n molecule s o wound up t h a t some of t h e end-groups of h y d r o x y l y s i n e were physically inaccessible? O r w a s e i t h e r t h e amino o r t h e h y d r o x y l group o f p a r t of t h e h y d r o x y l y s i n e bound i n some o r g a n i c c o m b i n a t i o n , such as acetylation. E v e n t u a l l y i t w a s shown i n a n o t h e r l a b o r a t o r y t h a t i n t h e h y d r o x y l y s i n e r e s i d u e s t h a t do n o t r e a c t w i t h p e r i o d a t e t h e hydroxyl groups a r e bound by g l y c o s i d e l i n k a g e t o g a l a c t o s e , and t h a t p a r t of t h e g a l a c t o s e i s a l s o l i n k e d t o glucose. 91 D r . 0.: The h y d r o x y l y s i n e w i t h t h e g l y c o s i d e l i n k a g e does not r e a c t with periodate. D r . V.: It w a s n o t a m a t t e r of t h e t e r t i a r y p r o t e i n f o r m a t i o n b e i n g one t h a t made t h i s p a r t i n a c c e s s i b l e , it w a s a c o v a l e n t combination of t h e h y d r o x y l y s i n e h y d r o x y l w i t h t h e s u g a r t h a t made t h e h y d r o x y l y s i n e i n e r t t o periodate. Dr. 0.: I would imagine t h a t some o f t h e work done h e r e on t h e Medical s i d e i s " b a s i c s c i e n c e " and I imagine t h e r e i s some s i m i l a r i t y t o the s o r t of e x p e r i m e n t a l s t u d i e s t h a t a r e done i n Biology. Is i t based p r i - m a r i l y on t h e i n t e r e s t s of t h e men who happen t o be t h e r e i n t h o s e po- s i t ions? Dr. V.: Yes, t h a t ' s a l s o t h e s i t u a t i o n i n t h e Biology Department. At t h e s t a r t of t h e Brookhaven when I f i r s t came i n t o i t , t h e r e w a s a g e n e r a l q u e s t i o n w i t h r e g a r d t o t h e p o l i c y of Brookhaven L a b o r a t o r y whether the work h e r e s h o u l d be l i m i t e d to work t h a t involved a t o m i c e n e r g y , radio- a c t i v i t y , etc.---- Dr. 0.: Yes, t h a t ' s a n i n t e r e s t i n g p o i n t . Dr. V.: T h a t i s , whether Brookhaven should do o n l y work t h a t c o u l d n o t be done anywhere e l s e , o r w h e t h e r t h e f i e l d a t Brookhaven s h o u l d be gen- e r a l , b u t p r o v i d i n g f a c i l i t i e s t h a t would make i t p o s s i b l e t o c a r r y problems i n t o p a t h s t h a t would b e d i f f i c u l t t o g e t i n t o w i t h o u t t h e p a r - t i c u l a r f a c i l i t i e s here. T h a t i s , w h e t h e r , f o r example, i n a problem s t a r t e d i n u s i n g atomic e n e r g y , i f you g o t t o a p o i n t where you d i d n ' t 92 need atomic e n e r g y anymore you'd have t o s t o p and s a y " I ' v e g o t t o quit." I w a s o n t h e s i d e t h a t s t o o d o u t f o r t h e b r o a d e r p o l i c y and I t h i n k i t became a c c e p t e d t h a t Brookhaven g i v e s you s p e c i a l f a c i l i t i e s b u t i t d o e s n ' t f o r c e you t o l i m i t y o u r problems t o t h o s e t h a t r e q u i r e such f a c i l i t i e s . I n a l l of t h i s work, as a m a t t e r of f a c t , on hydroxy- l y c i n e , a l m o s t a l l o f i t h a s been based o n u s e of r a d i o a c t i v e t r a c e r s . And i n some of i t t h i s c a r b o n 14 method t h a t I spoke o f , i t h a s proved very useful. Oh, o u r t r o u b l e i n t h e M e d i c a l Department i s t o hang o n t o o u r good men. T h a t happens t o e v e r y p r o d u c t i v e l a b o r a t o r y . D r . 0.: C e r t a i n l y t h e p h y s i c a l p l a n t h e r e i s so d i f f e r e n t from being i n t h e m i d s t of a n u r b a n c e n t e r where y o u ' r e hemmed i n by t h e r a p i d p a c e , i n a s e n s e , by c i v i l i z a t i o n . T h i s i s r e a l l y l i k e b e i n g o u t on a farm, literally. And you have e v e r y t h i n g you r e q u i r e , I ' m s u r e , f o r y o u r l a b o r a t o r y work r i g h t h e r e . I would t h i n k p e r h a p s the o n l y shortcoming would be i f a n o c c a s i o n a l w i f e would be u p s e t a t having t o be so f a r removed from some of the conveniences of c i t y l i f e ! D r . V.: Y e s , I t h i n k t h a t has happened, b u t i t ' s not s o f a r from N e w York t h a t people c a n ' t go i n f o r t h e a t e r . When t h e Medical Department h e r e was b e i n g o r g a n i z e d t h e r e w a s q u i t e s t r o n g p r e s s u r e b r o u g h t t o have t h e Brookhaven Medical Department i n New York C i t y . D r . 0.: F o r h e a v e n ' s sake! D r . V.: Yes. The i d e a was t h a t t h e Brookhaven M e d i c a l Department would be s o r t of a s e r v i c e department t o l a b o r a t o r i e s and h o s p i t a l s i n t h e c i t y and I s t o o d o u t a g a i n s t t h a t . I t h o u g h t i t ought t o be h e r e where it c o u l d u t i l i z e t h e s e u n i q u e f a c i l i t i e s , and t h e a s s o c i a t i o n w i t h c h e m i s t s , p h y s i c i s t s , and b i o l o g i s t s o f B.N.L., t o produce o r i g - i n a l research. D r . 0.: I w a s going t o s a y , i t would s o r t of d e f e a t t h e purpose o f h a v i n g t h e s e u n i q u e f a c i l i t i e s immediately a v a i l a b l e t h i s way. Dr. v.: Yes. D r . 0.: I g a t h e r t h e r e a r e many g r a d u a t e s t u d e n t s from t h e A s s o c i a t e d U n i v e r s i t i e s and I g u e s s from o t h e r s t o o , who spend v a r y i n g p e r i o d s of time h e r e working i n d i f f e r e n t l a b o r a t o r i e s ? Dr. V.: Yes, p a r t i c u l a r l y i n t h e summertime. T h e r e h a s been a d e f i n i t e program of summer s t u d e n t s coming o u t h e r e , t h a t i s , up t o t h i s y e a r . They a r e n o t o n l y a c c e p t e d , b u t t h e i r e x p e n s e s a r e p a i d . It had t o b e c u t down, a t l e a s t i n t h e Medical Department t h i s y e a r and I g u e s s e v e r y - where e l s e , t o o , i n Brookhaven because of t h e t i g h t money. D r . 0.: I t ' s b e i n g f e l t t h r o u g h o u t t h e government. Dr. V.: I hope i t w o n ' t l a s t t o o long. We l o s t one of o u r good men, K a t s i a n o s , a c h e m i s t , t h a t went t o t h e new M t . S i n a i Medical School. We h a v e n ' t g o t enough money t o r e p l a c e him. T h a t i s , t h e r e had t o be a c o s t of l i v i n g i n c r e a s e t o o t h e r s a l a r i e s and so f o r t h s o t h a t a l t h o u g h I t h i n k Brookhaven h a s been t r e a t e d a s w e l l as any of t h e government l a b - o r a t o r i e s , i t h a s n ' t been q u i t e w e l l enough t o keep even. I t ' s not a 94 c a s e of r u n n i n g t o s t a y where you a r e , when you c a n ' t even r u n q u i t e that fast. Dr. 0.: It's regrettable. I ' m a f r a i d i t ' s going t o g e t worse b e f o r e i t g e t s b e t t e r u n l e s s something d r a s t i c happens as f a r a s t h e f i n a n c i a l commitments t h e c o u n t r y h a s . Dr. V.: I t ' s made worse by t h e i n f l a t i o n which o r i g i n a t e d i n t h e p r e v i o u s f i n a n c i a l a d m i n i s t r a t i o n of t h e c o u n t r y . D r . 0.: Well, we c e r t a i n l y have e v e r s i n c e . Dr. V.: It means t h a t you have a c o n t i n u a l u p s e t of y o u r e q u i l i b r i u m among d i f f e r e n t c l a s s e s o f people. I remember s i t t i n g n e x t t o t h e Vice- P r e s i d e n t o f one o f t h e b i g c o r p o r a t i o n s . H e w a s t h e i r economic a d v i s e r and he had f o l l o w e d t h e c o u r s e of i n f l a t i o n i n Germany a f t e r World War I--had been i n Germany p a r t of t h e t i m e , and h e s a i d what happened was t h a t the s o l i d middle c l a s s had g o t wiped o u t . The v e r y w e a l t h y p e o p l e were a b l e t o m a n i p u l a t e and dodge s o t h a t t h e y hung on t o what t h e y had and ended up by owning e v e r y t h i n g ! And t h e l a b o r i n g c l a s s - - t h e y had t o g e t enough t o e a t ; t h e y k e p t on g e t t i n g t h a t , t h e i r wages had t o go up a s t h e v a l u e of t h e mark went down, b u t i t w a s a complete d i s l o c a t i o n o f t h e economy i n t h a t the p e o p l e t h a t were r e s p o n s i b l e f o r much of the p r o s p e r i t y o f t h e c o u n t r y were e l i m i n a t e d . D r . 0.: And t h i s i s w h a t ' s happening h e r e now. Dr. V.: We're s t a r t e d i n t h a t d i r e c t i o n . 95 D r . 0.: The growing d i s c o m f o r t a n d , I t h i n k , i m p a t i e n c e o f t h s c l a s s , t h i s g r o u p , t o o , i n o u r c o u n t r y is becoming more v o c a l c e r t a i n y o Such groups forming as t h o s e r e f u s i n g t o pay t h e i r income t a x u n t i l t h e y c l o s e t h e l o o p h o l e s f o r t h e v e r y wealthy. Dr. V.: I t h i n k t h i s d e f i c i t philosophy i s a v i c i o u s thing. I have never s t u d i e d i t b u t I c a n s e e t h e e f f e c t s of i t . D r . 0.: We a r e s e e i n g t h e e f f e c t s of i t , c e r t a i n l y . D r . V.: It amounts t o r u n n i n g u p d e b t s f o r your s u c c e s s o r s t o pay. What happened i n Germany was t h i s t e r r i f i c d i s l o c a t i o n and I t h i n k t h a t N a z i i s m w a s one o f t h e r e s u l t s of i t . D r . 0.: Could w e l l be. You c u r r e n t l y a t Brookhaven a r e f r e e d of adm n i s t r a t i v e r e s p o n s i b i l i t i e s and your t i m e i s devoted f u l l y t o t h e l a b o r a o r y . D r . V.: Yes, t h e l a b o r a t o r y and w r i t i n g of t h i s book on manometric methods. Yes, I ' m q u i t e f r e e from a d m i n i s t r a t i v e work now. D r . 0.: Which i s as i t should be I would t h i n k . What g o a l s do you have f o r t h e f u t u r e o t h e r t h a n completing t h i s book? With such a f e r t i l e and p r o f i t a b l e p a s t what o t h e r t h i n g s would you l i k e t o d o , s a y on t h e c o m p l e t i o n of t h i s book on manometric methods? D r . V.: W e l l , I would l i k e t o c o n t i n u e t h i s work on c o l l a g e n . It's t h e s o r t of t h i n g t h a t , l i k e most r e s e a r c h , you do i t from s t e p t o s t e p . 96 I t ' s n o t a u s u a l t h i n g i n r e s e a r c h t h a t you c a n t e l l s e v e r a l s t e p s ahead what y o u ' r e g o i n g t o do----- D r . 0.: No, of c o u r s e not. Dr. v.: -----b e c a u s e each s t e p f o l l o w s from t h e n e x t one and I ' d l i k e t o c o n t i n u e d o i n g t h a t as l o n g as my i n t e l l e c t u a l and p h y s i c a l f a c u l - t i e s h o l d up. When I f e e l t h e y h a v e n ' t why t h e n I ' l l r e a l l y r e t i r e . I ' v e been v e r y f o r t u n a t e , p h y s i c a l l y , so f a r . D r . 0.: A s we were s a y i n g t h e o t h e r day, n o t on t a p e , you c o n t i n u e t o play tennis quite regularly. Dr. V.: I s t i l l p l a y doubles. Dr. 0.: T h a t ' s marvelous. No, I suppose I asked t h a t q u e s t i o n t h i n k i n g p o s s i b l y o t h e r t h a n t h e c o l l a g e n work t h a t y o u ' r e d o i n g , whether o r n o t you had i n t h e back of y o u r mind, a n o t h e r a r e a t h a t you would l i k e t o a t t a c k . Dr. V.: No, I h a v e n ' t any p l a n s t o go i n t o a n o t h e r f i e l d . I f we r a n o u t of problems on t h e c o l l a g e n , t h e r e a r e enough o t h e r f i e l d s t h a t I have b e e n a c t i v e i n t h a t I c o u l d t a k e up a g a i n . Dr. 0.: Yes, t h a t ' s t r u e , t h a t ' s t r u e . Dr. V.: The c o l l a g e n work i s r e a l l y a c o n t i n u a t i o n of work on amino a c i d s t h a t I began when I f i r s t went t o t h e R o c k e f e l l e r I n s t i t u t e w i t h Levene. He p u t m e t o work on p r o t e i n s . T h a t was s h o r t l y a f t e r F i s c h e r ' s 97 e s t e r method f o r i s o l a t i n g amino a c i d s from hydrolyzed p r o t e i n s had come o u t and we s t a r t e d working w i t h t h a t . Then we needed some method f o r f o l l o w i n g t h e h y d r o l y s i s o f a p r o t e i n ; a method t o d e t e r m i n e e i t h e r t h e c a r b o x y l g r o u p s o r t h e amino groups t h a t a r e s e t f r e e when t h e p e p t i d e l i n k s a r e broken. I n a n amusing way I came t o work o u t the n i t r o u s a c i d method t o d e t e r m i n e t h e amino groups. I had t h e g e n e r a l problem i n t h e back of my m i n d - - t h a t was i n 1910. I went up t o Woods Hole t o work i n t h e F i s h Commission l a b o r a t o r y d u r i n g t h e summer, and came down w i t h t y p h o i d f e v e r and was t r a n s f e r r e d t o t h e M a s s a c h u s e t t s General Hospital. They had some wards t h a t were i n l i t t l e wooden b u i d - i n gs t h e n . Dr. 0.: Oh, t h e y s t i l l had t h e o u t b u i l d i n g s f o r i s o l a t o n and c o n t a - gious cases? D r . V.: Yes, t h e y s a i d t h e y t h e n went back f i f t y y e a r s t h o s e one- s t o r y wards. They were b u i l t a t a time when t h e i n f e c t ous t h e o r y o f d i s e a s e was f i r s t a c c e p t e d . T h e r e was no known way t o s t e r i l i z e b u i l d - i n g s and t h e y were b u i l t w i t h t h e d e l i b e r a t e i d e a t h a t t h e y would b u r n them down. Then i t was found t h a t you c o u l d s t e r i l i z e them w i t h s u l p h u r d i o x i d e and s o f o r t h , so t h e y were s t i l l t h e r e and I w a s p u t i n one of t h o s e wards. I g o t d e l i r i o u s , as i s common i n t y p h o i d , and I s t i l l remember a p e c u l i a r e x p e r i e n c e . I w a s v e r y hazy when I went i n . I went up by r a i l w i t h my w i f e from Woods Hole and walked i n and w a s p u t t o bed and I w a s v e r y h a z y f o r a day o r two. Then one n i g h t j u s t a s it was g e t t i n g dusk, my mind c l e a r e d up. I c o u l d n ' t remember how I g o t where I was. I was i n a room--it w a s n ' t a v e r y s t y l i s h room a t a l l - - i t was 98 very bare. It d i d n ' t l o o k good! And I d i d n ' t f e e l good, and I was i n bed b u t I c o u l d n ' t s e e my c l o t h e s anywhere--'bhere the devil am I and how d i d I g e t h e r e ? ' ' And I f i g u r e d I must have been f o u l l y d e a l t w i t h and dragged some p l a c e , b u t why I w a s n ' t k i l l e d w h i l e t h e y were a t i t I d i d n ' t know. I l a y t h e r e and s p e c u l a t e d o n i t and a woman came in. She had a n u r s e ' s u n i f o r m o n , b u t f o r some r e a s o n o r o t h e r I doubted t h a t s h e w a s a nurse. And I s a i d , ''Where am I?" She s a i d , "Oh, be q u i e t , you have t o be s t i l l . " I s a i d , "Well, I ' d l i k e t o know where I am." She s a i d , "You have t o be s t i l l . " T h a t ' s a l l I c o u l d g e t o u t of her. Oh, and t h e n s h e s a i d , "You're i n a hospital." Well, I was v e r y s k e p t i c a l a b o u t t h a t and I s a i d , "Well, i f I ' m i n a h o s p i t a l I ' d l i k e t o s e e t h e i n t e r n who's i n c h a r g e o f me.'' "Oh, t h e i n t e r n c a n ' t be d i s t u r b e d now; h e ' s o f f duty." W e l l t h e n I w a s damned s u r e t h a t t h e r e was something phony a b o u t i t . I w a i t e d u n t i l s h e went o u t and I g o t o u t of bed; I had o n l y been s i c k a few days so I was s t i l l s t r o n g . I g o t o u t of bed and t h e r e w a s a window a b o u t s i x f e e t from t h e ground and i t had a heavy s c r e e n on i t and I h i t t h a t s c r e e n w i t h my f i s t and t o r e i t l o o s e and was a b o u t t o s l i p o u t of t h e window----- D r . 0.: For h e a v e n ' s sakes! Dr. V.: -----when a n o r d e r l y came i n . He was a l o n g , l a n k y I r i s h l a d w i t h r e d h a i r - - I g o t t o be good f r i e n d s w i t h him a f t e r w a r d s - - a n d he had e x t r a o r d i n a r y p r e s e n c e o f mind. H e j u s t s l i p p e d up behind me and p u t h i s arms around my c h e s t - - c a r e f u l n o t t o p u t them around my abdomen-- and j u s t hung o n , he j u s t hung on u n t i l I g o t t i r e d o f s t r u g g l i n g and I gave up and g o t back i n t o bed. He t o l d me a f t e r w a r d t h a t I so begged him 99 t o g e t me o u t o f t h i s dump, t h a t he a l m o s t w a s i n tears h i m s e l f ! But I ' v e t h o u g h t s i n c e t h a t i f t h e n u r s e had t a l k e d t o m e l i k e a s e n s i b l e b e i n g , t h a t t h a t w o u l d n ' t have happened. D r . 0.: Given you some e x p l a n a t i o n . D r . V.: And it would be a good i d e a i f more p e o p l e knew t h a t a b o u t handling people i n delirium. They may n o t be c o m p l e t e l y crazy! Even- t u a l l y , I was i n the c a r e of D r . R i c h a r d Cabot, and I remember he came t o my door and s a i d , "You've g o t p o s i t i v e W i d a l ; y o u ' r e g o i n g t o be h e r e f i v e weeks!" F i v e weeks from t h a t day I w a s l e t o u t . I t o l d my n u r s e t h a t and s h e s a i d , "Yes, i t w a s k i n d of a j o k e t h e p o s i t i v e prognoses t h a t Richard Cabot makes. We had a man come one day and wanted t o be a d m i t t e d and nobody c o u l d f i n d what w a s t h e matter w i t h h i m and t h e y asked him why he wanted t o b e a d m i t t e d and ' W e l l , ' he s a i d , ' j u s t a y e a r ago tomorrow D r . Cabot s a i d I had e x a c t l y one y e a r t o live!"' (Laughter) Cabot went i n t o s o c i a l s e r v i c e work l a t e r . D r . 0.: He was r a t h e r a remarkable f i g u r e . D r . V.: Yes h e w a s . A f t e r I came o u t of t h e d e l i r i u m and t h e f e v e r went down, t h e l a s t c o u p l e o f weeks t h a t I w a s t h e r e were t e r r i b l y b o r i n g because I w a s n o t s i c k , b u t I w a s n ' t p e r m i t t e d t o g e t u p - - j u s t had t o l i e t h e r e , and so I amused myself by t h i n k i n g of w h a t e v e r I c o u l d and I g o t t o t h i n k i n g a b o u t t h i s problem of f o l l o w i n g p r o t e i n h y d r o l y s i s by d e t e r m i n i n g e i t h e r t h e c a r - boxyl o r the amino groups. W e l l , i n my work w i t h Gomberg, I had done a 100 g r e a t many d i a z o t i z a t i o n s i n s y n t h e s i z i n g compounds, and i t o c c u r r e d t o me t h a t i t might be p o s s i b l e you c o u l d d i a z o t i z e a l i p h a t i c amino groups and s p l i t o f f t h e n i t r o g e n t h e same as you could w i t h a r o m a t i c s and t h a t t h a t might answer t h e problem. My w i f e used t o spend e v e r y day w i t h m e from n i n e t o f i v e and s h e ' d w r i t e a p o s t c a r d t o my f a t h e r t e l l i n g him how I w a s . T h i s i d e a came t o me and one t h i n g t h a t l a s t e d a f t e r the d e l i r i u m was gone was t h a t I had no memory! That i s , I ' d f o r g e t t h i n g s i n f i v e minutes! My w i f e s a i d i f something s t r u c k me funny, I ' d t e l l h e r t h e same s t o r y and s h e ' d have t o l a u g h a t i t t e n t i m e s d u r i n g t h e day! D r . 0.: You had memory f o r d i s t a n t p a s t b u t n o t f o r t h e immediate p a s t . 6 D r . V.: Yes. W e l l , I w a s a f r a i d I ' d f o r g e t t h i s i d e a , s o as s h e was w r i t i n g t o my f a t h e r and I s a i d , ''I've g o t a n i d e a and I want you t o t a k e i t down (she was a c h e m i s t s o s h e c o u l d do i t ) ; I want you t o t a k e i t down because I'm a f r a i d I ' l l f o r g e t it.'' She s a i d , " I ' l l w r i t e it.'' And s h e k e p t on w r i t i n g and what s h e was w r i t i n g was: ''Don i s b e t t e r b u t h e ' s s t i l l c r a z y i n the head!'' She d i d n ' t w r i t e i t down a t a l l . But i t happened t h a t I d i d remember i t . And when I g o t back t o t h e l a b o r a t o r y , I t r i e d i t o u t and a f t e r I g o t d e t a i l s worked o u t i t became t h e n i t r o u s a c i d method f o r d e t e r m i n i n g amino a c i d s . We used it among o t h e r t h i n g s t o d e m o n s t r a t e t h a t f r e e amino a c i d s c i r c u l a t e i n t h e blood and t h e amount t h a t i s t a k e n up from t h e i n t e s t i n e d u r i n g d i g e s t i o n i s s u f f i c i e n t t o a c c o u n t f o r a l l t h e n i t r o g e n metabolism. D r . 0.: I t ' s remarkable how t h i s t i e s back t o your i l l n e s s . 101 D r . V.: But t h a t w a s a funny way t o g e t it. Yes, i f I had s t a y e d w e l l and busy p r o b a b l y I might n o t have t h o u g h t o f i t . D r . 0.: A q u e s t i o n t h a t comes t o mind which w i l l b e somewhat d i f f i c u l t t o e x p r e s s and maybe something we w i l l s c r a t c h o u t o f t h e t r a n s c r i p t , b u t b e i n g a n " a n a l y t i c a l chemist", I mean as a c l i n i c a l b i o c h e m i s t , and having even a t t h a t p o i n t become involved somewhat w i t h c l i n i c a l b i o - c h e m i s t r y , when you were i n t h e s i t u a t i o n a s a p a t i e n t , d i d you have any t h o u g h t s a b o u t t h e p r a c t i c e of medicine a s you s a w i t , i n o t h e r words, a s you were s u b j e c t e d t o i t a s a p a t i e n t ? Perhaps w i t h t h o u g h t s of some of t h e s e tremendous v o i d s and t h i n g s t h a t were l a c k i n g . R e a l l y some of your l a t e r e x p e r i m e n t a l m r k d i d f i l l a tremendous v o i d which had g r e a t a p p l i c a t i o n i n t h e p r a c t i c e of medicine. I n o t h e r words, d i d you a t a n y t i m e f i n d y o u r s e l f , whether a s a p a t i e n t o r under o t h e r c i r c u m s t a n c e s , r e a c t t o t h e way medicine w a s p r a c t i c e d i n t h o s e days. D r . V.: W e l l , a t the Rockefeller Hospital I think there was very close t o a n i d e a l p o i n t of view w i t h r e g a r d t o t h e h a n d l i n g of p a t i e n t s . D r . 0.: Yes. But w a s n ' t t h i s p e r h a p s u n i q u e i n t h e s e n s e t h a t t h a t i s n ' t t h e way t h a t medicine i s r e a l l y p r a c t i c e d t h r o u g h o u t t h e c o u n t r y . D r . V.: I was c h i e f l y concerned w i t h l e a r n i n g a s much o f t h a t procedure a s I could and s e e i n g t h e p a t i e n t s t h a t were i n my c h a r g e (because a f t e r I g o t i n t o t h e k i d n e y work t h e p a t i e n t s were r e a l l y i n my c h a r g e ) were handled n o t o n l y c o r r e c t l y b u t s y m p a t h e t i c a l l y . O c c a s i o n a l l y I would know, as one d o e s , of c a s e s where t h e m e d i c a l p r o f e s s i o n e i t h e r i n hos- p i t a l s o r i n p r a c t i c e had d i s t i n c t l y l e s s e r i d e a l s . I d o n ' t remember t h a t i t o c c u r r e d t o me t h a t t h e i d e a l s of m e d i c i n e , a s t h e y were a t t h e R o c k e f e l l e r under D r . Cole, could be improved. Dr. 0.: No, I ' m s u r e t h a t ' s t h e c a s e . I was t h i n k i n g r e a l l y more of y o u r exposure t o medicine a s p r a c t i c e d i n g e n e r a l a t p l a c e s o t h e r t h a n t h e R o c k e f e l l e r and not j u s t t h e e t h i c s o r what-have-you, but a c t u a l l y t h e s t a t e of t h e i r k n o w l e d g e - - t h e i r s c i e n t i f i c knowledge--which i n s o many c a s e s , o f c o u r s e , was = w h a t i t was a t t h e R o c k e f e l l e r . Dr. V.: I was always i n t e r e s t e d i n t h a t - - b o t h t h e e t h i c s and t h e p r a c - tice. I remember I w a s o c c a s i o n a l l y s u r p r i s e d by b o t h what one might c a l l t h e h i g h d e g r e e o f competence of p r a c t i t i o n e r s - - o r d i n a r y p r a c t i - tioners--and the opposite. D r . 0.: The h i g h d e g r e e of i g n o r a n c e , too. Dr. V.: The e t h i c s - - i t ' s a good i d e a t h e p u b l i c d o e s n ' t know t h e w o r s t of it. O c c a s i o n a l l y p e o p l e would c a l l m e , somebody I knew would be i n New York, and a s k t o b e d i r e c t e d t o a d o c t o r . There was a d i s t a n t cou- s i n o f mine from San F r a n c i s c o - - s h e w a s buyer i n a b i g s t o r e t h e r e - - came t o New York----- [End of Side I , Reel 31 [ S i d e 2 , R e e l 31 Recorded May 28, 1969. Dr. V.: - - - - -s h e c a l l e d me and s a i d t h a t s h e had been p r e t t y busy and had a l o t of d i n n e r s i n New York and s h e g o t t o f e e l i n g u n c o m f o r t a b l e and went t o a d o c t o r i n t h e s e v e n t i e s on Park Avenue, which i s a s t y l i s h 103 medical p a r t of New York, and h e t o l d h e r t h a t she had t o have two o p e r a t i o n s immediately and t h a t t h e y would c o s t h e r $1500 and he wanted h e r t o b e o p e r a t e d o n t h e n e x t day: D r . 0.: Good God! Dr. V.: That s o r t of took h e r b r e a t h away so s h e c a l l e d me up. I sent h e r t o a good p r a c t i t i o n e r I knew, and a l l she needed was a dose of Epsom salts: D r . 0.: U n f o r t u n a t e l y , t h i s s o r t of t h i n g s t i l l happens. D r . V.: Another t h i n g . A man came t o work w i t h me from Chicago, h e ' d been a n A s s i s t a n t P r o f e s s o r t h e r e . H i s w i f e was a l s o a n M.D. and a n Ann Arbor g r a d u a t e - - t h a t was my own school. A f t e r they got married, i n o r d e r t o be i n t h e same town w i t h him, s h e took a j o b i n a p r i v a t e h o s p i t a l i n Chicago. It was a h o s p i t a l t h a t s o f a r a s p a p e r s were con- cerned was i n p e r f e c t l y good s t a n d i n g . She found, a f t e r s h e ' d been t h e r e long enough t o s e e what w a s going on, p a t i e n t s who d i d n ' t need o p e r a t i o n s were r e f e r r e d by p r a c t i t i o n e r s i n Chicago. A c a s e where a n appendectomy, f o r example, would be r e f e r r e d f o r appendectomy, i n t h a t h o s p i t a l t h e y ' d j u s t s l i t t h e s k i n open and sew i t up a g a i n and t h e p a t i e n t would be l e t o u t and would t h i n k h e ' d made a v e r y good recovery. When t h e r e was a r e a l l y s e r i o u s c a s e , t h e y were l i k e l y t o g e t i n t r o u b l e . I t ' s a good t h i n g t h e p u b l i c d o e s n ' t know t h o s e t h i n g s . D r . 0.: Yes. Well, i n t h i s day and a g e , t o o , t h e r e ' s some element of informing them through some of t h e s e books t h a t come o u t l i k e I n t e r n and Doctor X. 104 Dr. V.: On t h e o t h e r hand, i n c o n t r a s t , f o r s e v e r a l y e a r s when my c h i l d r e n were v e r y l i t t l e - - 1 had a boy and a g i r l - - w e s p e n t t h e summer i n a camp on S k a n e a t e l e s Lake i n t h e F i n g e r Take r e g i o n of w e s t e r n New York, and one time when we g o t up t h e r e (my l i t t l e g i r l w a s a b o u t f o u r y e a r s o l d ) I n o t i c e d t h e next day a f t e r we g o t t h e r e she went around pressing her throat. I took h e r t e m p e r a t u r e and she had a d e f i n i t e tem- perature. There was a l o c a l d o c t o r t h e r e - - i t was j u s t a l i t t l e v i l l a g e - - and I went up t o g e t him and he came down, a man a b o u t f o r t y , and he t o o k a s t i c k and looked i n my d a u g h t e r ' s t h r o a t and he s a i d , "Doctor, I ' d l i k e t o have you look a t t h i s . " There was a membrane a l l over t h e tonsils. He s a i d , "I know t h a t t h e p r o p e r t h i n g i s t o g e t a c u l t u r e and make s u r e of t h i s , b u t I have s e e n d i p h t h e r i a b e f o r e and I t h i n k t h a t i f you a g r e e t o i t t h a t we'd b e t t e r s t a r t serum a s soon as we can!" We were about 20 m i l e s from Syracuse and I s a i d , "Yes, of course." I f i g u r e d i t would b e a c a s e of going up t o Syracuse t o g e t t h e serum and he s a i d , "I'll be r i g h t back." He g o t i n t o h i s c a r and went up t o h i s o f f i c e and came back w i t h some p e r f e c t l y good brand new serum and he gave everybody i n t h e camp ( a f t e r t e s t i n g everybody f o r s e n s i t i v i t y ) a n immunizing dose and a t h e r a p e u t i c dose f o r my d a u g h t e r and i n 24 hours t h e membrane was gone: I g o t a c q u a i n t e d w i t h him. He used t o come down o c c a s i o n a l l y and v i s i t w i t h me. He had a n i n t e r e s t i n g h i s t o r y . His name was Twining. D r . 0.: Twining? Dr. V.: Twining. He was a nephew of Arthur Twining Hadley who had been P r e s i d e n t of Yale. He was graduated from t h e medical s c h o o l i n B u f f a l o , 105 and he came t o t h i s p l a c e which was c a l l e d Borodino from t h e p l a c e where Napoleon f o u g h t t h e Russians. H e came t o t h i s p l a c e t o t a k e p r a c t i c e d u r i n g t h e summer of a n o l d p h y s i c i a n who wanted t o rest. T h a t was j u s t a f t e r Twining had h i s i n t e r n s h i p , and t h e o l d p h y s i c i a n never came back! Twining l i k e d t o h u n t and f i s h and it was r i g h t on S k a n e a t e l e s Lake and t h e people t h e r e were o l d - t i m e American s t o c k . He g o t t o know t h e l o c a l people and t o l i k e them and so he s t a y e d on t o t a k e c a r e of them and ended up by marrying one of t h e l o c a l g i r l s and s t a y i n g t h e r e f o r good! He used t o go t o Syracuse Medical School f o r a r e f r e s h e r c o u r s e so he k e p t up t o d a t e . And he was a n e f f i c i e n t , d e d i c a t e d f a m i l y d o c t o r . Thank God, h i s i d e a l i s t h e r u l e and n o t t h e e x c e p t i o n . D r . 0.: We might j u s t s a y , f o r t h e r e c o r d , I know we were speaking of your son, Karl K e l l e r , who i s now a surgeon i n p r a c t i c e i n t h e Nassau H o s p i t a l i n Mineola on Long I s l a n d . And your d a u g h t e r ? D r . V.: Daughter? She's a s e c r e t a r y w i t h t h e Du P o n t ' s i n Wilmington. S h e ' s been w i t h them f o r t w e n t y - f i v e y e a r s . The Du Pont Company t r e a t s i t s employees v e r y w e l l . D r . 0.: I n o t i c e d t h a t you've had t h e unique e x p e r i e n c e , and I ' m s u r e p l e a s u r e , of p u b l i s h i n g a paper w i t h both your f a t h e r and a l s o w i t h your son, which I t h i n k i s q u i t e unique i n t h e a n n a l s of medicine and s c i e n c e . D r . V.: Yes, t h e f i r s t p i e c e of work t h a t I p u b l i s h e d , a s a m a t t e r of f a c t , was p u b l i s h e d b e f o r e my t h e s i s g o t o u t t h a t I d i d w i t h Gomberg; t h e f i r s t work was done w i t h my f a t h e r . He was an e x p e r t on t h e chem- i s t r y of m i l k and he was i n t e r e s t e d i n and d i d q u i t e a good d e a l of work 106 on c a s e i n . He was working w i t h one of h i s a s s i s t a n t s , Ed H a r t , who a f t e r w a r d s became P r o f e s s o r of A g r i c u l t u r a l Chemistry i n Wisconsin. They found when c a s e i n was p r e c i p i t a t e d w i t h a c i d t h a t some o f t h e a c i d stuck t o the casein precipitate. Also i f t h e p r e c i p i t a t e d c a s e i n was washed w i t h w a t e r u n t i l t h e w a t e r was n e u t r a l and t h e n shaken w i t h d i l u t e a c i d i t would combine w i t h some of t h e a c i d . The q u e s t i o n was: What was t h e n a t u r e of t h e combination? Was i t p h y s i c a l o r c h e m i c a l ? I had been t a k i n g p h y s i c a l c h e m i s t r y a t Michigan. I had a v e r y good t e a c h e r of p h y s i c a l c h e m i s t r y , P r o f e s s o r G. A. Hewlett. He w a s a p u p i l of Ostwald. He was a b o u t 30 t h e n and f u l l of enthusiasm, and I took a l l t h e p h y s i c a l c h e m i s t r y t h a t was given. Hewlett w a s a marvelous t e a c h e r . I f I went t o him w i t h a q u e s t i o n , h i s answer would be t o g i v e me a r e f e r e n c e i n t h e l i t e r a t u r e and i f I c o u l d n ' t u n d e r s t a n d i t h e ' d h e l p me work i t o u t . I j o i n e d f a t h e r on t h e c a s e i n problem d u r i n g t h e sunnner v a c a t i o n of 1906. We were a b l e t o show t h a t c a s e i n took up a c i d by a p r o c e s s t h a t had t h e c h a r a c t e r i s t i c s of p h y s i c a l a b s o r p t i o n . The a c i d was n o t t a k e n up i n t h e way t h a t i t would behave i f i t were a chemical combination. Greatly d i f f e r e n t amounts of d i f f e r e n t a c i d s w e r e t a k e n up, w i t h o u t r e l a t i o n t o t h e i r strength a s acids. I measured t h e amounts t h a t were t a k e n up by doing c o n d u c t i v i t i e s on t h e s u p e r n a t a n t s which gave a v e r y s e n s i t i v e measure. The procedure d e l i g h t e d my f a t h e r , who had grown up b e f o r e c o n d u c t i v i t i e s were done. D r . 0.: You were s t i l l i n c o l l e g e a t t h e time. T h i s w a s d u r i n g sunnner vacation? 107 D r . V.: I was s t i l l i n college. T h i s was t h e y e a r b e f o r e my f i n a l y e a r a t Ann Arbor. My f i a n c e e had no mother o r e s t a b l i s h e d home, so my people i n v i t e d h e r o u t t o spend t h e summer and, as I have s a i d , s h e had been t a k i n g a c h e m i s t r y c o u r s e a t Ann Arbor. She j o i n e d t h e work on t h e problem; my younger b r o t h e r , who w a s a p r e t t y good mathematician, did the calculations. Dr. 0.: For h e a v e n ' s s a k e s , i t w a s r e a l l y a f a m i l y production! Dr. V.: My f a t h e r had a house on t h e Experiment S t a t i o n s i t e - - i t was r i g h t a c r o s s t h e road from t h e l a b o r a t o r y and we'd g e t t h i n g s s t a r t e d a t 7 o ' c l o c k i n t h e morning, t h e n I ' d go back home and have b r e a k f a s t . We'd keep experiments going u n t i l suppertime. A f t e r supper we'd p l a y tennis. I n t h e c o u r s e of t h e summer, we g o t a j o b done t h a t would o r d i n a r l y have t a k e n a y e a r , and i t w a s a c c e p t e d by t h e American Chemica J o u r n a l which w a s t h e b e s t j o u r n a l we had then. That was pub- l i s h e d by I r a Remsen, of Johns Hopkins. The American Chemical S o c i e t y had begun t o p u b l i s h i t s j o u r n a l but Remsen's j o u r n a l was t h e most r e s p e c t a b l e chemical j o u r n a l w e had i n America then. D r . 0.: A s I remember, I r a Remsen, upon t h e opening of t h e Medical School a t Hopkins, t a u g h t t h e c o u r s e i n c h e m i s t r y f o r medical s t u d e n t s and t h e n t h e y f i n a l l y got----oh d e a r , t h e man t h a t C l a r k followed. His name s l i p s me a t t h e moment--the f i r s t P r o f e s s o r of Chemistry a t t h e Medical School. D r . V. : Remsen was one of t h e Americans who went t o Germany i n t h e l a t e 1800s and brought German s c i e n c e back t o t h i s country. He was a 108 great teacher. He came t o Ann Arbor and gave t h e comnencement a d d r e s s one time w h i l e I w a s t h e r e . I remember v e r y few of t h e s p e a k e r s t h a t I ' v e h e a r d i n my l i f e t i m e , a s one d o e s , b u t I remember Remsen. He be- came P r e s i d e n t of Hopkins. He ntended t o c o n t i n u e h i s s c i e n t i f i c work, b u t he found i t was impossible. Most people who have t r i e d t o combine t h a t e x t e n t of e x e c u t i v e work w t h r e s e a r c h f i n d i t a n impossible t h i n g . I f y o u ' r e a n e x e c u t i v e you belong t o t h e people t h a t work w i t h you. If anybody c a n s a y " h e ' s my c h i e f " t h a t ' s a r e a l p o s s e s s i v e , he Owns you! The p o p u l a r i d e a may be t h a t t h e c h i e f p o s s e s s e s h i s s u b o r d i n a t e s ; r e a l l y they possess t h e chief! They have a r i g h t t o a c c e s s t o him and t o h i s time and t o demand h i s h e l p and t h a t h a s p r i o r i t y over any p r i v a t e pro- j e c t s t h a t he may l i k e t o c a r r y o u t . Dr. 0.: You know t h i s i s t h e d e c i d i n g f a c t o r I ' m s u r e , f o r many p e o p l e , t h e age-old problem of t h e competent s c i e n t i s t who h a s made a name f o r himself and c o n t r i b u t e d t o t h e f i e l d , t h e n t h e n e x t s t e p p i n g s t o n e i n so many p e o p l e ' s e y e s is t o make him Chairman of a department and t h e n more a d m i n i s t r a t i v e work and s o on, i t removes him from h i s bench. Dr. V.: I f he h a s v e r y good s u b o r d i n a t e s t h a t he c a n keep w i t h him, he c a n keep going f o r a w h i l e by working by proxy, and t h a t ' s n o t l i k e l y to last. D r . 0.: I think i t ' s very interesting. One of t h e t h i n g s t h a t was s o obvious was D r . H a s t i n g s ' tremendous d e l i g h t a t g e t t i n g back t o t h e bench when he l e f t Harvard and g e t t i n g t o S c r i p p s . He was l i k e a kid: J u s t bubbling o v e r w i t h j o y a t g e t t i n g h i s hands on t h e i n s t r u m e n t s again. L 109 D r . V.: Yes, he loved Harvard and Margaret loved t h e s o c i a l s i d e t h e r e , but t h e chance of g e t t i n g away from a d m i n i s t r a t i v e work and back t o t h e l a b o r a t o r y tempted him t o go t o La J o l l a and I d o n ' t t h i n k he e v e r r e g r e t t e d it. He l i k e d t o t e a c h , h e l i k e d t o t e a c h ; he s a i d i t was a c o n t i n u a l s t i m u l u s t o be i n c o n t a c t w i t h t h o s e v e r y f i n e young minds. Of c o u r s e , t h e Harvard medical s t u d e n t s were a h i g h l y s e l e c t e d bunch, t h e same a s t h e Hopkins ones. There was g r e a t d i f f e r e n c e between Harvard College and t h e Harvard Medical School i n t h e r e l a t i o n of t h e s t u d e n t s t o each o t h e r . D r . 0.: T h a t ' s very i n t e r e s t i n g . Dr. V.: My son went through t h e c o l l e g e and t h e medical s c h o o l b o t h a t Harvard. The s t u d e n t s i n t h e c o l l e g e had n o t been r e l a t e d t o each o t h e r l i k e comrades a t a l l ; t h e y were more l i k e people l i v i n g i n apartment houses i n a b i g c i t y . Harvard t r i e d t o overcome i t . I n o r d e r t o do t h a t , t h e system of houses f o r t h e s t u d e n t s t o l i v e i n d u r i n g t h e i r l a s t t h r e e y e a r s of c o l l e g e was d e v i s e d . Each house had a c o u p l e of hundred s t u d e n t s and a housemaster, and t h e s t u d e n t s were supposed t o g e t on a f i r s t name b a s i s w i t h each o t h e r . The freshmen were a l l p u t i n t h e Yard. A l a r g e p a r t of t h e freshman c l a s s were boys from prep s c h o o l s i n New England, where, i f you were w i s e , you s e n t your son i n c a s e you wanted him t o g e t i n t o Harvard and l a s t through t h e f i r s t y e a r . Harvard Col- l e g e took i n 1200 freshmen and dropped 400 of them. D r . 0.: Good Lord: I had never r e a l i z e d t h a t . 110 Dr. V.: Yes, t h a t w a s t h e i r p o l i c y . And i n o r d e r t o s t i c k you had t o be i n t h e upper t w o - t h i r d s . Well, t h e s e p r e p s c h o o l s t r a i n e d t h e i r boys t o meet t h e s i t u a t i o n . T h e i r t e a c h e r s knew e x a c t l y what t h e i r s t u - d e n t s would g e t e v e r y day a t Harvard i n t h e i r freshman y e a r . They t r a i n e d them t o g e t i n t o t h a t f i r s t t w o - t h i r d s . I f a boy came from even a v e r y good p u b l i c school--my boy came from t h e B r o n x v i l l e High School, which was a v e r y good h i g h s c h o o l - - t h e y were a t a d i s a d v a n t a g e i n com- p e t i n g w i t h t h e p r e p s c h o o l boys. The h i g h s c h o o l boys and t h e p r e p s c h o o l boys never d i d mix v e r y much. K e l l and two o t h e r boys t h a t went from B r o n x v i l l e had a n apartment on t h e t o p f l o o r of one of t h e houses i n t h e Yard and t h e r e was a n o t h e r apartment f o r t h r e e boys on t h e o t h e r side. They d i d n ' t speak t o each o t h e r f o r a b o u t s i x weeks and t h e n t h e y g o t t o g e t h e r because it was advantageous t o g e t a t e l e p h o n e o u t i n t h e h a l l between them, and t h e y found t h e y l i k e d each o t h e r . But i t a p p a r - e n t l y w a s n ' t t h e t h i n g t o do t o f o r c e y o u r s e l f on anybody e l s e . Then t h e second y e a r , K e l l was i n one of t h e houses and i t w a s n ' t any b e t t e r . He s a i d i f you go down and s i t n e x t t o a n o t h e r boy and you asked him t o p a s s t h e s a l t , h e ' d p a s s i t b u t i t d i d n ' t mean t h a t you became a c q u a i n t e d w i t h each o t h e r . As soon as K e l l g o t i n t o medical s c h o o l it was completely changed; t h e Medical School w a s l i k e one b i g f r a t e r n i t y . He moved i n t o V a n d e r b i l t H a l l and w h i l e he was s t i l l moving i n some of t h e upper classmen came i n and i n t r o d u c e d themselves and s a i d t h a t t h e y would be g l a d t o h e l p i n any way t h e y could. And from t h a t t i m e i t was a d i f f e r e n t s c h o o l . 111 Dr. 0.: It i s a c o n t r a s t . I know when you s t a r t e d , I t h o u g h t w e l l , I e x p e r i e n c e d something l i k e t h i s m y s e l f , I suppose, a t two t o t a l l y d i f - ferent institutions. A t l e a s t t h e camaradarie and t h e l o n g - s t a n d i n g f r i e n d s h i p s one made i n medical s c h o o l a r e f a r g r e a t e r t h a n c o l l e g e . But t h i s i s v e r y unique, I t h i n k , i n a s e n s e a t t h e same i n s t i t u t i o n t o have a c o n t r a s t l i k e t h a t . D r . V.: I d o n ' t know whether Harvard i s unique. D r . 0.: I s h o u l d n ' t s a y unique t o Harvard, b u t p o s s i b l y more c h a r a c t e r - i s t i c of some of t h e Ivy League s c h o o l s where you have a number of f e l - lows from prep s c h o o l s who have known each o t h e r through p r e p s c h o o l and s t i l l remain a c l i q u e , i n a s e n s e , when t h e y g e t t o c o l l e g e . D r . V.: That was c o m p l e t e l y d i f f e r e n t from a n y t h i n g t h a t I knew i n Ann Arbor a Dr. 0.: I'm s u r e , D r . V.: The Midwest i s d i f f e r e n t . I f I was i n a c l a s s t h e r e w i t h an- o t h e r f e l l o w and somebody asked me i f I knew him, I ' d say y e s , of c o u r s e I w a s i n a c l a s s w i t h him. It was a p e c u l i a r s i t u a t i o n i n Harvard Col- l e g e ; nobody l i k e d it. Dr. 0.: And y e t t h e y w o u l d n ' t t a k e s t e p s t o change it. D r . V.: S t e p s were t a k e n b u t t h e y d i d n ' t work. It was j u s t t h e i n e r t i a was s o g r e a t . I d o n ' t know any o t h e r word t o e x p r e s s i t . It was j u s t a v e r y p e c u l i a r p s y c h o l o g i c a l phenomenon. 112 Dr. 0.: Was D r . H a s t i n g s son i n your s o n ' s c l a s s ? Dr. V.: H a s t i n g s ' son you s a y ? No, he w a s younger; q u i t e a b i t younger. Young H a s t i n g s i s doing j u s t what he l o v e s nowo He's a P r o f e s s o r of Music a t T r i n i t y College. He had a most e x t r a o r d i n a r y mind. I remember when he was a b o u t twelve y e a r s o l d I v i s i t e d H a s t i n g s i n Chicago, and t h e young Baird had j u s t w r i t t e n a t h e s i s on t h e Supreme C o u r t - - p a r t of h i s English course. I r e a d i t and i t was t h e most i l l u m i n a t i n g d e s c r i p - t i o n of t h e r o l e t h a t t h e Supreme Court had played i n t h e development of o u r working c o n s t i t u t i o n t h a t I r e a d anywhere. Dr. 0.: A t t h e age of twelve: D r . V.: Yes, a t t h e age of twelve. He c o u l d have been a q u i z k i d be- cause he could t e l l you most any h i s t o r i c a l d a t e and t h e c i r c u m s t a n c e s around i t t h a t you might a s k f o r . When he g o t i n t e r e s t e d i n music he had t h e same t y p e of e n c y c l o p e d i c memory f o r a n y t h i n g i n music. He'd p u t a r e c o r d on and b e f o r e he'd h e a r d t h r e e b a r s h e ' d know what i t was and probably could t e l l you what o r c h e s t r a played i t . But h e d i d n ' t l i k e science. D r . 0.: No, I g a t h e r e d he s o r t of followed M r s . H a s t i n g s ' fondness f o r a r t and music and so on. Dr. V.: May I a s k how i t came to----you took t h i s work i n medical history? D r . 0.: Well, i t s t a r t e d o f f as a hobby. I found myself spending a l l of my s p a r e time r e a d i n g and w r i t i n g i n t h e h i s t o r y of medicine. This 113 began w h i l e I w a s a s u r g i c a l r e s i d e n t and by t h e time I completed f i v e y e a r s o f s u r g i c a l t r a i n i n g and gone i n t o p a t h o l o g y , I e s s e n t i a l l y s p e n t a l l of my s p a r e time i n t h i s manner. I d i d n ' t w r i t e any s c i e n t i f i c p a p e r s a t a l l w h i l e I was a p a t h o l o g i s t . Everything I w r o t e was i n medical h i s t o r y . My c h i e f a t t h a t time was q u i t e sympathetic t o t h i s ; he thought i t was f i n e . And t h e o p p o r t u n i t y came t o go t o t h e L i b r a r y . I was l i t e r a l l y f i n i s h i n g up my r e s i d e n c y i n pathology a t N I H and g o t a phone c a l l from t h e D i r e c t o r of t h e L i b r a r y who s a i d "I understand y o u ' r e i n t e r e s t e d i n medical h i s t o r y and t h e problems of biomedical com- munication?" and I s a i d , "Yes." I went o v e r and had lunch and t h a t was i n J u l y o r p r i o r t o J u l y , of 1964 which i s when I went t o t h e L i b r a r y . A f t e r one y e a r , I was f u l l time i n t h e h i s t o r y of medicine; thoroughly enjoyed i t , I r e a l l y have. D r . Vo: Yes. Well, I can u n d e r s t a n d it. I a m f a s c i n a t e d by h i s t o r y m y s e l f , b u t I never had time t o spend on i t t h a t I ' d l i k e t o . T e l l me, do you t h i n k medicine made any p r o g r e s s a t a l l d u r i n g t h e c e n t u r i e s a f t e r t h e Roman Empire broke up? D r . 0.: U n t i l t h e Renaissance you mean, i n o t h e r words through t h e medieval p e r i o d ? D r . V.: Yes. D r . 0.: Well, i t ' s g e n e r a l l y looked upon a s being a p e r i o d of some s t a g n a t i o n and t h e p e r i o d where t h e r e c o r d s of t h e p a s t were passed a l o n g p r a c t i c a l l y unchanged w i t h v e r y s l i g h t m o d i f i c a t i o n , by t h e suc- c e e d i n g many g e n e r a t i o n s and t h e c h r o n i c l e r s of medicine, a s it were, 114 i n t h e r e l i g i o u s i n s t i t u t i o n s of t h e day. D r . V.: P r a c t i c a l l y e v e r y t h i n g w a s c a r r i e d on through t h e Church, w a s n ' t i t ? The monks were t h e o n l y people t h a t knew how t o r e a d : D r . 0.: Yes. It was t h e b i g problem. They were t h e people who l i t e r - a l l y preserved, i n a sense, the western heritage. And, i n t i m e , a g a i n t h i n g s s t a r t e d o u t t o blossom o u t i n new d i r e c t i o n s , o f t e n t i m e s a t a l e v e l f a r below t h e educated man w i t h your b a r b e r surgeons and what- have-you. It took many, many y e a r s f o r them t o become r e s p e c t a b l e and medicine w a s q u i t e pompous and v e r y s t i l t e d i n i t s ways and t h e educated p h y s i c i a n r e a l l y w a s n o t v e r y w e l l - e d u c a t e d i n medicine a t a l l . Whereas your uneducated man who was t r e a t i n g p a t i e n t s i n t h e small communities was l e a r n i n g a good d e a l more medicine, b u t h e was n o t recognized by t h e academicians. It took q u i t e some w h i l e f o r t h i s t o mold i n t o one. D r . V.: Dr. Cole was v e r y much i n t e r e s t e d i n medical h i s t o r y - - I think p a r t i c u l a r l y i n t h e development of medicine when i t w a s coming o u t of t h e d a r k ages. I remember h i s q u o t i n g a n I t a l i a n F l o r e n t i n e , I t h i n k it was Redi. Dr. 0.: Francesco R e d i ? Dr. V.: Yes. Dr. 0.: Spontaneous g e n e r a t i o n . Dr. v.: Redi s a i d t h e d i f f e r e n c e between no p h y s i c i a n and a good phy- s i c i a n i s n o t g r e a t but t h e d i f f e r e n c e between no p h y s c i a n and a bad physician is very great! Redi w r o t e a famous poem i n p r a i s e of wine, I think. It took a long time f o r t h e d o c t r i n e of l a u d a b l e pus t o disappear. Dr. 0.: Oh y e s . Yes, i n my work on D r . H a l s t e d , reviewing t h e s t a t u s o f s u r g e r y i n t h e l a t e 1 9 t h c e n t u r y and e a r l y 20th c e n t u r y , i t ' s remarkable t o s e e t h e s t e p s t h a t were t a k e n and haw t h i s was approached-- t h e f a c t t h a t t h e r e were surgeons who wore g l o v e s between o p e r a t i o n s b u t not a t surgery. D r . V.: Yes? D r . 0.: Yes., There were some who s a i d you should keep your hands pro- t e c t e d t o keep them c l e a n so t h a t when you come t o o p e r a t e , you s e e , you h a v e n ' t exposed them t o a l l t h e s e t h i n g s . Then t h e r e were t h o s e who used j u s t f i n g e r c o t s t o p r o t e c t t h e m s e l v e s , you s e e , from contamination. And D r . H a l s t e d h i m s e l f who is g i v e n c r e d i t f o r i n t r o d u c i n g r u b b e r g l o v e s i n t o g e n e r a l use i n s u r g e r y by a l l members of t h e team d i d n o t i n t r o d u c e g l o v e s a s a n a s e p t i c method a t a l l . It was simply t h a t h i s s c r u b n u r s e had developed a tremendous s k i n r e a c t i o n t o t h e m e r c u r i c c h l o r i d e so he approached t h e Goodyear Rubber Company t o s e e i f t h e y ' d make a p a i r of t h i n r u b b e r g a u n t l e t s which she would wear when s h e picked t h e i n s t r u - ments up o u t of t h e b a s i n of m e r c u r i c c h l o r i d e and passed them on t o t h e next man i n l i n e . A f t e r a w h i l e h i s f i n g e r s s t a r t e d t o b o t h e r him so he j u s t s t a r t e d wearing t h e g l o v e s t o p r o t e c t h i s hands from t h i s s t u f f . Dr. V.: That's interesting. D r . 0.: And it w a s n ' t u n t i l Joseph Bloodgood, who was one o f H a l s t e d ' s r e s i d e n t s , some f o u r y e a r s l a t e r s t a r t e d t o r o u t i n e l y wear them f o r a s e p t i c purposes i n t h e o p e r a t i n g room. Dr. V.: Well, I suppose t h e y would have been i m p r a c t i c a l u n l e s s they could have been made v e r y t h i n because a surgeon depends on touch so much. D r . 0.: Well, t h i s h e l d it back f o r some w h i l e . Many surgeons r e f u s e d t o wear them f o r t h i s r e a s o n , t h a t was t h e argument, t h a t t h e y had t o have t h e i r s e n s e of touch. Some would t a k e t h e glove o f f and s t i c k t h e i r hand i n t h e wound, f e e l i t and t h e n p u t t h e glove back on. Others used v e r y f i n e c o t t o n and l i n e n g l o v e s . They f e l t t h e y could f e e l b e t t e r through t h e s e w i t h o u t t h e t e n s i o n of t h e r u b b e r g l o v e on t h e i r hand. D r . V.: I guess a l l p a t h o l o g i s t s wear g l o v e s when t h e y do a n a u t o p s y now, d o n ' t t h e y ? D r . 0.: To my knowledge, yes. Yes, I ' d s a y so. Again, t h e r e a r e p e r - haps some s e n i o r members who----- Dr. V.: ---- thought i t w a s n ' t q u i t e masculine. D r . 0.: -----y e s , would come i n and n o t b o t h e r t o p u t on a glove j u s t t o h a n d l e some t i s s u e s o r something you were showing them, b u t I t h i n k t h e y a l l do now. One of t h e two s e n i o r r e s i d e n t s i n s u r g e r y when I was a n i n t e r n a t Hop- k i n s was o p e r a t i n g on a TB c a s e and t h e y were working down i n t h e c h e s t . 117 They were doing a pulmonary r e s e c t i o n and t h e a s s i s t a n t r e s i d e n t , q u i t e by a c c i d e n t , working i n a f i e l d where t h e v i s i b i l i t y w a s n ' t too good was t a k i n g a Kocher clamp t o clamp a bronchus and he g o t t h i s chap's f i n g e r and he g o t a s o f t - t i s s u e t u b e r c u l o u s i n f e c t i o n . It k e p t him from o p e r a t i n g f o r f o u r months of h i s twelve months of r e s i d e n c y - - f o u r months o r more. He c o u l d n ' t go i n t h e o p e r a t i n g room. D r . V. : Did t h e y s a v e t h e f i n g e r ? D r . 0.: Oh yes. Saved t h e f i n g e r and i t f i n a l l y c l e a r e d up, but i t came a t a r a t h e r bad time because i t i n t e r r u p t e d t h e - - t h a t ' s t h e one y e a r , of c o u r s e , i n t h e seven-year r e s i d e n c i e s when y o u ' r e r e a l l y a b l e t o c a r r y on a l o t of s u r g e r y because i n t h a t pyramid system t h e y have a t Hopkins you s t a r t o f f doing a b s o l u t e l y n o t h i n g as a n i n t e r n t h e r e . I f you make a move even t o p i c k up t h e s u t u r e t o hand t h e r e s i d e n t , t h e a s s i s t a n t r e s i d e n t whacks your hand; you j u s t s t a n d t h e r e w i t h t h e s c i s s o r s and c u t i t . o n c e i t ' s been t i e d . You d o n ' t t a k e t h a t n e x t s t e p . So you have t o w a i t a w h i l e b e f o r e you do much s u r g e r y . D r . V.: A l o t of p a t h o l o g i s t s have picked up TB, and t h a t ' s a shame. D r . 0.: Because o f t e n t i m e s i t ' s c l i n i c a l l y n o t s u s p e c t e d and y o u ' l l g e t i n t h e a u t o p s y room and n o t be wearing a mask--you'll be i n a gown and gloves. D r . V.: One of my s o n ' s c l a s s m a t e s who went i n t o pathology g o t TB; he g o t over i t , got i t a r r e s t e d . But i t took him some time t o g e t i t arrested D r . 0.: Oh, i t ' s s t i l l a p r e v a l e n t d i s e a s e , t h e r e ' s no q u e s t i o n of that D r . V.: But people now d o n ' t r e a l i z e what a scourge t u b e r c u l o s i s used t o be. And I d o n ' t know t h a t i t ' s c e r t a i n a l t o g e t h e r why i t h a s dimin- i s h e d so much. Dr. 0.: T o some d e g r e e , I suppose, e a r l i e r d e t e c t i o n p l u s i n g e n e r a l b e t t e r health conditions. Dr. V.: General c o n d i t i o n s a r e b e t t e r ; a s f a r a s I know t h a t ' s about a l l one can say. D r . 0.: I t ' s s t i l l v e r y p r e v a l e n t , c e r t a i n l y i n t h e low income groups. [Pause - Tape o f f ] Dr. V.: The E l i L i l l y Pharmaceutical Company, I t h i n k , was v e r y generous i n t h e i r support of basic science. I served a s a d v i s e r i n t h e d i s t r i b u - t i o n of about f o u r hundred thousand d o l l a r s a y e a r f o r f i v e y e a r s . I v i s i t e d c o l l e a g u e s i n u n i v e r s i t i e s i n t h i s c o u n t r y and Europe, and made reports t o Lilly. I t h i n k t h a t 90 p e r c e n t of t h e recommendations I made were honored by t h e L i l l y people. Dr. 0.: (Examining some notebooks of D r . Van Slyke) Are t h e s e more o r l e s s notebooks of your i m p r e s s i o n s of t h e s e v a r i o u s departments and what- have-you and what was going on i n s c i e n c e i n t h e s e v a r i o u s a r e a s ? Dr. V.: Those a r e t h e l i t t l e books. Yes, t h e y ' r e n o t e s of i n t e r v i e w s 119 I had w i t h people and d a t e s t h a t I made i n my work f o r L i l l y . It w a s very interesting. I s p e n t two o r t h r e e months each y e a r t r a v e l i n g f o r L i l l y between 1951 and 1956. The L i l l y ' s were v e r y n i c e people t o work w i t h . I said I didn't care t o t r a v e l w i t h o u t my w i f e and t h e y a p p o i n t e d h e r a s my t r a v e l i n g s e c r e - t a r y , and s h e was a godsend. S h e ' s Danish and f a m i l i a r w i t h c o n t i n e n t a l people and when I ' d been t a l k i n g w i t h c o l l e a g u e s a l l day long and t h e n we'd be a t a d i n n e r , thank God she could t a k e over. D r . 0.: That i s a godsend! D r . V.: When we were on o u r way o u t t o Taiwan i n ' 6 1 , our t r a v e l agency f o r g o t t o g e t v i s a s s o we stopped on t h e way o u t a t Tokyo and I was warned t h a t I ' d have t r o u b l e g e t t i n g t r a n s p o r t a t i o n from Japan t o Taiwan i f I d i d n ' t have a v i s a . So I went around t o t h e Chinese c o n s u l a t e and t h e man t h e r e s a i d t h a t t h e y ' d have t o c o n s u l t w i t h Taiwan and i t would t a k e s e v e r a l days. Well, I was due t o l e a v e t h e n e x t day. By good l u c k , I had a l e t t e r from t h e Chinese Surgeon-General i n my pocket. He'd w r i t t e n welcoming u s t o Taiwan. I drew t h a t o u t and t u r n e d i t over t o t h e c o n s u l a t e and he went o u t i n t h e o t h e r room and came back a l l s m i l e s and welcome and s a i d e v e r y t h i n g w a s OK. Dr. 0.: That's very interesting. Was t h i s u n i q u e , you t h i n k , t o t h i s p a r t i c u l a r time o r i s i t always t h a t way a s f a r a s g e t t i n g i n t o Taiwan. D r . V.: I d o n ' t t h i n k i t was unique f o r t h a t time. I think it is p a r t of t h e defense of Taiwan a g a i n s t Communist i n f i l t r a t i o n , b u t t h e y ' r e v e r y c a r e f u l who comes i n from Japan, because t h e Comnunists from t h e mainland could come i n t h a t way and t h e Taiwan government d o e s n ' t want t o have any u n n e c e s s a r y t r o u b l e t h a t might be imported t h a t way. They h a v e n ' t had any youth r e v o l t i n Taiwan. They have v e r y h i g h s t a n d a r d s i n t h e i r schools there. P h i l l i p s ' children--at l e a s t some of h i s c h i l d r e n - - w e n t t o Chinese s c h o o l s and t h e y p r o g r e s s e d , as n e a r l y a s I could make o u t from t h e i r mathematics, somewhat f a s t e r than o u r c h i l d r e n do. They work s i x days a week. They d o n ' t have S a t u r d a y s o f f , and i f t h e y ' v e had d i f f i c u l t i e s t h e y c a n s e e t h e i r t e a c h e r s on Sunday t o g e t caught up. And o n l y t h e upper 10 p e r c e n t can go t o c o l l e g e and o n l y a v e r y s m a l l p e r c e n t a g e of t h o s e c a n go t o medical school. Dr. 0.: I t ' s q u i t e a c o n t r a s t t o some o t h e r s i t u a t i o n s , i s n ' t i t ? D r . V.: Yes, I t h i n k t h a t P h i l l i p s ' d a u g h t e r going t o a Chinese s c h o o l t h e r e w a s b e t t e r t a u g h t t h a n she would b e going t o many of t h e h i g h s c h o o l s i n t h i s country. We're n o t going t o s t a y ahead of Asia i n d e f - initely! D r . 0.: I b e l i e v e i t was D r . H a s t i n g s who had mentioned t h a t t h e y were t o l d by one of t h e academicians i n Taiwan t h a t t h e y were n o t g i v i n g any advanced d e g r e e s - - 1 d o n ' t know i f t h i s was i n b i o c h e m i s t r y o r j u s t what s u b j e c t - - u n t i l t h e y f e l t t h a t t h e q u a l i t y of t h e i r t e a c h i n g and f a c u l t y and so o n was a b l e t o match any w e s t e r n c o l l e g e s . I n o t h e r words, t h e y w e r e n ' t diploma m i l l s by any m a t t e r of meanso They were f u l l y c o g n i z a n t of t h e needs of h i g h e r e d u c a t i o n . D r . V.: No, t h e y recognized t h e d e s i r a b i l i t y of s t a n d a r d s . They're 121 d o i n g work t h a t ' s c o n s i d e r e d sound i n t h e new n u c l e a r p l a n t i n Taiwan. Some e x c e l l e n t Chinese advanced s t u d e n t s have come o v e r t o t h i s c o u n t r y t o g e t e d u c a t e d t o go back. The American Bureau f o r Medical Aid t o China f o r a good many y e a r s h a s had s e v e r a l f e l l o w s e a c h y e a r i n t h i s country--some o f them f a c u l t y members, some of them younger men t h a t were f a c u l t y t i m b e r . I t h i n k t h e r e ' s o n l y one that h a s n ' t gone back. They c o u l d s t i c k t o t h i s c o u n t r y and g e t b e t t e r j o b s and b e t t e r f a c i l - i t i e s i n which t o work. D r . 0.: I t ' s i n t e r e s t i n g so many have gone back and t h i s may a g a i n be characteristic. T h i s i s a c o n t r a s t t o some of t h e o t h e r c o u n t r i e s where i t ' s a s e r i o u s problem, p e o p l e coming o v e r h e r e i n s c i e n c e and medicine and s t a y i n g . Dr. V.: The R o c k e f e l l e r F o u n d a t i o n h a s had t h a t problem w i t h European Fellows. I ' v e t a l k e d w i t h Foundation D i r e c t o r s about it. They put a l l t h e p r e s s u r e t h e y c a n on and t h e y h a v e agreements t h a t t h e s e boys would go back t o t h e i r own c o u n t r i e s , b u t t h e y d o n ' t always h o l d . Dr. 0.: And I g u e s s when t h e c h i p s a r e down t h e r e ' s n o t a g r e a t d e a l t h e y c a n do t o f o r c e them. D r . V.: Some of them were j u s t i f i e d i n s t a y i n g because of c o n d i t i o n s a t home. T h e r e were two S p a n i a r d s t h a t came o v e r t o t h e R o c k e f e l l e r I n s t i t u t e from Barcelona b e f o r e t h e R e v o l u t i o n i n Spain. Then t h e R e v o l u t i o n broke o u t and t h e I n s t i t u t e t h e y were t o go back t o j u s t d i d n ' t g e t going. So t h e y s t a y e d on. One of them m a r r i e d my w i f e ' s daughter. J o r d i Casals, a virologist. He gave t h e Theobald Smith L e c t u r e a c o u p l e o f weeks ago on v i r o l o g y a t t h e R o c k e f e l l e r I n s t i t u t e . He's w i t h t h e R o c k e f e l l e r Foundation and a l s o h a s a p r o f e s s o r s h i p a t Yale. And t h e o t h e r one w a s J o r d i F o l c h who came t o work w i t h m e f o r a y e a r and t h e n t h e r e v o l u t i o n broke o u t so he c o u l d n ' t go back. He came on a R o c k e f e l l e r Foundation F e l l o w s h i p and he t o o k h o l d so w e l l t h a t he was a p p o i n t e d a r e g u l a r a s s i s t a n t s h i p w i t h a s a l a r y and s t a y e d w i t h me s e v e n y e a r s . Then he became head o f t h e McLean H o s p i t a l l a b o r - a t o r y which is connected w i t h H a r v a r d , and h e ' s s t i l l t h e r e . He's a Harvard p r o f e s s o r . [End of S i d e 11, R e e l 31 INDEX Addis, Thomas, 19 A l l e n , F. M., 22-23, 25, 72 A l s b e r g , C a r l , 69-79 American Bureau f o r M e d i c a l Aid t o China, 40-41, 52, 1 2 1 American Chemical J o u r n a l , 107 Amino a c i d s t u d i e s , 8 , 87-91, 99-101 A n f i n s e n , C h r i s t i a n B o , 36, 77 Aronson, Robert B., 89 A r t e r i a l p u n c t u r e , o r i g i n o f , i n c l i n i c a l medicine, 48-49 A s t r u p , P o , 76-77 Avery, Oswald T., 63-64 B e n e d i c t , S t a n l e y R., 22 Benison, S a u l , 34 B i n g e r , C a r l A. L., 44 Biochemische Z e i t s c h r i f t , 55 Blake, F r a n c i s G., 47 Blake, John B., 47 Blood s p e c i f i c g r a v i t y measurement (copper s u l f a t e method), 57-59 Bloodgood, Joseph, 116 Bock, A r l i e , 44 Bohr, N i e l s , 65, 7 8 124 Bond, V i c t o r P., 86 Bronk, D e t l e v , 32-33 Brookhaven N a t i o n a l L a b o r a t o r y , Upton, L.I., 31, 52, 63, 81-87, 91-93 Cabot, R i c h a r d , 99 Carbon 14 s t u d i e s , 87 C a r r e l , A l e x i s , 1 7 , 66-68 Casals, J o r d i , 1 2 1 C a s e i n s t u d i e s , 105-107 C h o l e r a , 59-61 C l a r k , W i l l i a m M a n s f i e l d , 79-81 Cohn, A l f r e d E . , 70-71 Cohn, Edwin J., 70-71 Cole, Rufus, 30, 33, 4 8 , 102, 114 C o l l a g e n s t u d i e s , 87-91 C o r n e l 1 U n i v e r s i t y Medical S c h o o l , 22 C r o n k h i t e , Eugene , 87 C u l l e n , Glenn E., 22, 24, 26, 4 2 , 46 C u r t i s , Howard J . , 86 Cyanosis, s t u d i e s o f , 48 D i a b e t i c a c i d o s i s s t u d i e s , 22-25, 42-43 D i l l , D. Bruce, 44 Dochez, Alphonse R., 63 E i n s t e i n , A l b e r t , 65 E l i L i l l y P h a r m a c e u t i c a l Company, 118-119 125 F a r r , Lee E., 56-57, 85 F i r s t Chemical I n s t i t u t e ( B e r l i n ) , 9-11 F i s c h e r , F m i l , 8-13, 15-16, 26, 54 F l e x n e r , Simon, 7-8, 16-20, 30, 69-70 F o l c h , J o r d i , 122 F o l i n , O t t o K. O., 22 Gas and e l e c t r o l y t e e q u i l i b r i a s t u d i e s , 27-28, 36-39 Gerlach (Emil F i s c h e r ' s nephew), 12-14 Goldhaber, Maurice, 86 Gomberg, Moses, 6 , 14-15 Hadley, A r t h u r Twining, 104 Haldane e f f e c t , 76 Haldane, J. B. S., 74-75 Haldane, John S c o t t , 65, 74, 76 H a l s t e d , W i l l i a m S., 115 Hancock, (Miss), 4-5 H a r t , Edward, 106 Harvard C o l l e g e , 109-112 Harvard Medical School, 22, 109, 122 H a s s e l b a l c h , K. A., 76 H a s t i n g s , Alan B a i r d , 112 H a s t i n g s , A l b e r t B a i r d , 25, 27, 36, 39-40, 43-44, 7 1 , 76, 82-83, 88, 108-109 Hayworth, Leland, 83-86 126 H e i d e l b e r g e r , Michael, 27 Heimrod, 67 Henderson, Lawrence J., 37, 42-45 Hewlett, G. A . , 106 H i l l e r , Alma, 56, 87 Hobart C o l l e g e , 6 Hydroxylysine, 87-91 Johns Hopkins U n i v e r s i t y , 3 J o u r n a l of B i o l o g i c a l Chemistry, 55 Levene, Phoebus, A. T., 7-8, 16-18, 53, 70, 96 Levine, Sam, 7 1 Levy, R o b e r t , 7 1 Linderstrdm-Lang, Kai, 25, 77-79 Loeb, J a c q u e s , 65-66 Love, R o b e r t , 85 Lowry, O l i v e r H., 77 Lundsgaard, C h r i s t e n , 25-29, 48, 51, 7 6 McLean, F r a n k l i n C., 3 7 , 43 M a s s a c h u s e t t s General H o s p i t a l , 97-100 M e l t z e r , Samuel J . , 1 7 , 30 Meyer, Gustav, 53-54 Michigan, U n i v e r s i t y o f , 1-3, 6 , 62, 106, 111 M d l f e r , E g g e r t , 26 Morse, P h i l l i p , 82-83 127 New York S t a t e A g r i c u l t u r a l Experiment S t a t i o n , Geneva, N.Y., 3 , 7 , 107 Noguchi, Hidayo, 17 Opie, Eugene, 16-17 Oxygen i n h a l a t i o n t h e r a p y , o r i g i n s , 48-50 Palmer, W a l t e r W . , 43 P a r k e r , F l o r e n c e , 5-6 Peking Union Medical C o l l e g e , 36 P e t e r s , J a c k P., 20, 45-47, 51-52 P h i l l i p s , R o b e r t , 57-59, 1 2 1 P i k e , New York, 1 P l a z i n , John, 61, 8 7 Popenoe, Edwin, 88 P o t t e r , N a t h a n i e l Bowditch, 72-73 Punaha S c h o o l , Honolulu, H.I., 2 Q u a n t i t a t i v e C l i n i c a l Chemistry, 20-21, 45-46, 51-52 Redfield, Alfred C., 44 R e d i , F r a n c e s c o , 114-115 Remsen, I r a , 3 , 107-108 R i v e r s , Tom, 33-35 Robinson, Canby, 61-62 R o c k e f e l l e r F o u n d a t i o n , 44-45, 1 2 1 R o c k e f e l l e r I n s t i t u t e , 7-8, 16-18, 29, 31, 33-35, 68-69, 122 R o c k e f e l l e r I n s t i t u t e H o s p i t a l , 18-19, 22-23, 29-31, 33-35, 47-48, 62-63, 81, 1 0 1 R o c k e f e l l e r , J o h n D., Jr., 44-45 Rous, Peyton, 68 S a l v e s e n , Harold A . , 26 S a n t a Barbara C o t t a g e H o s p i t a l , 73 S i n e x , F. M a r o t t , 88 S d r e n s e n , S. P. L., 81 Stadie, W i l l i a m C., 28, 48-50, 74 S t e e l e , R o b e r t , 87 S t i l l m a n , Edward, 71-74 Taiwan, 119-121 T u b e r c u l o s i s , 116-118 Twining, D r . , 104-105 Typhoid f e v e r , 97-100 United S e r v i c e s f o r China, 41 U.S. Bureau of Chemistry, 7 , 69 U.S. N a t i o n a l I n s t i t u t e s o f H e a l t h , 35-36 U.S. Naval Medical Research Unit 2 (NAMRU 2 ) , 59 U n i v e r s i t y of Copenhagen, 26 Van S l y k e , K a r l K e l l e r , 105, 109 Van S l y k e , Lucius L., 1-3, 6-8, 62, 105-107 Warburg, E r i k , 76 Washington U n i v e r s i t y , School o f Medicine, S t . L o u i s , 18 Woods Hole, Laboratory of Biochemistry, Fish Comnission Laboratory, 79-80, 97 Wu, Hsien, 37-38 Zeitschrift fur Physiologia et Chemie, 55