Wednesdav, November 20 1 1968. Room 529 Main Science Building, New York University Medical Center, let Avenue & 32nd Street, New York City. What I'd like you to do today is to frenklv speculate. I want to know how you understand the traditions--human, spiritual. intellectual, physical-- the traditions to which you fell heir by virtue of being born Michael Heidelberger, traditions for which yoy are in no wise responsible. but a beginning, a point of departure. l know this is hazy. It's not en eve witness thing. It's the kind of feel that one hes as to one's origins-- the traces within which one grows and responds. They are elusive things. I wouldn't want to be any more clear than that. l'm not sure that I can be clearer, but in vour understanding. what is it that you fell heir to? Well, I think my parents were both very much interested in having their children get a good education. My father had had relatively little of it himself beyond just public school. My mother had gone to a good private school in Virginia where she was born and then even had a year afterwards in Germany, visiting relatives and getting ideas about German education. She taught my brother and me through the primary grades of public school. Neither of us went to school before the first grammar school grade. They probably don't divide school up that way any more, but that was the division then. In public schools I had some very good teach- ere end some rather poor ones • The ones that I liked were always invited .Jp.1 r-t~erd '-":--v--­ up to the houee for dinner. My parents talked with them and tried to see that that helped me along as much as poaaible. I made up my mind when 1 wae eight that I wanted to be a chemist, 2 but I didn't know why, of course. It was just a pigheaded idea, I suppose. I liked to mix medicines and things--just to see what would happen. Any- thing around the house I would put together and see what happened. a Mr.<!-u"'tis '"- ,,J Ona of the teachers in public schoo~--I guess around the time I was nine or ten--said that I ought to study physics first, that I ought to be exposed to physics and then if that didn't frighten me off, maybe I did want to be a chemist. My parents bought a little book called Cooley's Phy•ica which I looked at rather superficially. I more or less went my own way as before, but I think it was the very good science courses that first Henry A. Kelly gave at the old Workingman's School, later called the Ethical Culture School which I went to from my last year in grammar school through high school: the science course was four years of first botany, zoology, and then physics and chemistry under William E. Stark. These were really marvelous courses, and by that time I was fully determined to be a chemist. I don't know that there was any philosophy about it, except that going to the Ethical Culture Sunday School and to their eighth grade and high school I was exposed to all the formal religions. They started with Greek Mythology and went on up through. It was really a very thorough course in comparative religions and ethical values, and I guess I was receptive to that. In any event, I decided on an academic career in chemistry. There won't be any rhvme or reaeap to the Wf¥ in which we go at things. There are some things you indicated that I would like ta go back to. One of them ia Virginia--vour mother's source. Well, her parents came from Germany. Her father came from Odenwald, 3 I think it waa, wherever that may be, but I think it is up in the Harz District somewhere. Her mother came from Furth in Bavaria. They got rest­ less around, I guess, 1848--that time--and my grandfather came to America I first on a sailing ship. He started peddling goods in the South. He settled down in Norfolk, Virginia, and started a small shirt manufacturing business, and that was where his roots stuck. She had oppo;tynity in education. Yea--she had a good schooling in some young ladies academy down there. My father alwaya regretted that he didn't have a good schooling. Both of them were terribly fond of music. My mother played piano a bit. She tried to teach me ta play, but I was never interested in piano. She took me to opera when I was eight and to concerts tao. I remember very .......... well concerts at Manhattan Beach under Anton Seid-l who was supposed to ---- be one of the great German conductors of the time. Mueic--did you respond to music? Yes. When I got to high school and they started a high school orches­ tra, I started the clarinet, and I've been playing ever since. As soon as my father saw that I was serious, he let me get an A clarinet too. First I had only a B flat clarinet and then I had bath the B flat and A clari­ nets--and those are the instruments I'm still using. That's 9£88t--was your Dad bgrn and £pised in New Vork City? No, ha was• Philadelphia Republican. Wall! That needs some explanation! 4 He was born in Philadelphia. He had a brother who was out in Silver City, Idaho. All I know of my paternal grandfather is that I have a huge ring that belonged to him--I was named after him; he was Michael Heidel­ berger. I have an enormous golo ring that he wore--just on which finger I don't know. It's big enough for a thumb, I guess, but I never actually knew my paternal grandfather. He died either before I was ,born, or when I was very young. My father's mother I don't know anything about at all. My father had a very elemental sort of love of music. His favorite composition was the intermezzo from Cavalleria Rusticana, but the funny e thing is that when I began to study the Max Rjlger Clarinat Sonatas which are realiy quite difficult music, he liked the first sonata very much. I started with the number one sonata, and although a lot of it was pretty difficult music, my father often asked me to play that for him. That's ~ funny. It wasn't melodious--I mean it was not at all like~ favorite composition, but he liked it. He didn't remain in Philadelphia? No. I was born in New York. They were living in New York. He had a business making carriage robes with a distant relative whose last name was Frank--Jacob Frank. Jdcob Frank married a Miss Heidelberger who was no relative whatsoever. They were in business for a while, but carriages /Ylj £~t\i8f. went out very quickly, and Re- became a traveling salesman then fer, I guess, lap dusters, carriage robes, and finally curtaina--window curtains. He was usually away for almost six months of the year traveling. Of course, my mother took charge then, and she got rather authoritative as a result which was sort of natural, I think. 5 How did your mother and fethnr get together--ahe being in Virginia? I really don•t know. They never talked very much about that, but they wera very devoted to each other. I had a younger brother who was twenty-one months younger than I was. I wa ■ the second child actually. The first one died before I was born. My younger brother and I fought pretty much, I guese, as two boys of al­ most the eeme age would. He was really quite brilliant in many ways, could have gone on to college if he had wanted to, but he didn't went to. He wanted to make money in Well Street. He wee one of thees rare people who could whistle double notes. He taught himself to do that. That is rare. He could have been a pretty good pianist too, I think, if he had wanted to work at it. Where was the neighborhood where VDU ~ere brpught up in the City? On East 90th Streat until I began to go to college when we moved over ta West 93rd, end I've been living in that pert of the city ever since. Ware there books in the house? Yes, there were books, but not a very extensive library. We had ~ Dickens, Thacke~--mostly the classics. I read Dickens from eight on with- out understanding very much of it, I guess, at that period. That's a pretty good chore to chew on Dickens--it'e good stuff. 6 I liked Dicken• better than et-ttenry and Horatio Alger Jr. which was what most of the other boys were reading. The Horatio Alger stories were all the same. You read one of them, and you knew them all. I know--the grand repetition. Did vou get much opportunitv out to plav gn East 90th Street in those days? Yes, we used to play cherry pits in the cherry pit season, tops in the tops season, prisoner's base and all that sort of thing with the rest of the crowd on the street. Very often the lower 90th Street gangs would come up and rob us of everything we had. We'd try to fight them, but they usually overpowered us. We've onlv changed thet with respect to its intensitv 1 I auepect. Yes. I guess they fight with weapons now. We fought with our fists. It's kind of hard to assess the impact that one has on one's own neigh- borhood. It reallv is. Did vou have friends? Yes. There were a lot of boys who lived on the same block, and we used to play after school. I had a few friends in school. I went to Public School #6 first at 65th and Madison. How did vau t ■ ke to school? I got along reasonably well. There was one teacher who made me very self-conscious. She thought I asked questions in an impertinent way, and so I began modulating my voice to try to sound less impertinent, and I gueaa I got more and more ao all the time. She was the only teacher I 7 could never get along with. It may be something whol.v in her hearing. I don't know what it was. It's often said that whet one person says the other hears, and there may be no connection between the two. Yes. Were there any other teechere? This waa grammar school. Were these the days af homework? They didn't give ue very much homework then--no. It was only after I went ta the Ethical Culture School that they began to load you with homework, We had a lot there. There were wonderful courses there at the Ethical Culture School. They had men like Percival Chubb teaching English, and he had the moat beautiful resonant voice and knew all English litera­ ture--ha was really marvelous. - Then there was David SaQille Muzzey teaching history. the beet courses. Then thera was chemistry and physics, biology • These were . "A V'--':l ~end) 6-•..-t U-:'.(''{' dri'1t..L ie.-,21<.!.,k.t:y, w,,1; lhatd<id ..A 1.<..er bat-!£, 1<,Jltc• f'd"C bca,~i:"-\ul 00,.uiti ,i,t l'l<;;i1kev-.._,;d.~.c. I guaaa acme of the beat teachers turn out to be Pied Pipers. in a way. It'a not understood at the time 1 but they leave something somehow, They add to your luggage. Yes, I think certainly I was very much influenced in writing by Mr. Chubb. I didn't do very well in English at college becauae by that time I was specializing in chemistry and trying to express myself in aa brief 8 a way as possible. I'd write very ahcrt essays when they asked to have eaaays. They didn't like that. They wanted more--quantitatively mere. The teaching wasn't as good et the section level at Columbia. You know. the Ethical Cultut• Mqv,mant iteelf--were your parents part of this? Yea, they were members from the very beginning. Thia was an intellectual. spiritual thing with them. Yes. !h1t creates its own atmosphere. Yea, it really does. pid you hear relix Adler? Yes, I even had him aa an ethics teacher, and I'm afraid that I was a great disappointment to him because after--oh, this was in the l920's, I guess, at the Rockefeller Institute. I was working there, and Felix Adler wanted ma to organize a group of young scientists who would con ■ ider ethical problems and see whether the~ were reconcilable with their scien­ tific background--juet to think over ethical problems from the scientific point of view, but it would have meant reading a lot of books an ethical subjects end discussing for hours st s time probably. Nat one of us had the time ta do it. We had to begin to think about making our own careers. It would have involved an entirely disproportionate amount of time so that the whole project fell through, and I think it was s great disappointment 9 to him. Did you convey tbe difficulties that the ygung peoqle were confronting? Yee, I tried to, but Adler wasn't the type of person who brooked dif­ ficulties very readily. He did have• set of blinders, didn't he? Well, he was a very remarkable man, and he was always very wonderful to me. My first wife was a distant relative of hie wife, and so our fami­ lies were somewhat related, but the leader whom I was closest to was John Lovejoy Elliott. He was a marvelous person. So much of the grganizations, clubs, groups of which WE are a part take their tone from the pegple who heed them up end •••• Yea, of course. And Adler certainly wgs a pervasive influence in the Ethical Culture Move­ ment es was Elliott. Well, Adler, I think, appealed much more to older, mature persons than to the young. He was always a little bit aloof. He seemed a bit cold to young people, whereas Elliott was right there in the midst all the time. It ffl@>( be the momentum th9t !:Omes with one who ;j.s in a position ta give answers and one whc is still fumbling with theif pcseibilities and there­ fore deals mo;e di;ectlv with youngsters as Elliott might have dona. Well, he lived at one of the Settlement Houaes and was right in the 10 thick of all social difficulties, the troubles of the time. They were unaettled--weren•t they. Yes--there were troubles then too, but somehow they didn't seem as threatening ae they do now. I don't think they were either. Life was a little bit simpler. I think our rate of intake perhaps in thgee dava--vcu know, with respect to detail that goes on in the world wap leas than it ia today. Nothing can happen anywhere now but we don't know about it the next minute. Yes, that's true. It's ever prepent with ell the tensions which it creates, but--vou know, I've heerd--I don't know this--about Third Avenue coffee houses where you could argue all day and all night and hear various opinions from various points of view all the way from anarchists on down. Trotsky was an hebitu~ of one. An illuminating kind of education that we don't have time for appafentlv anv more. I was too busy studying then to take pert in discussions in the coffee shop. Besides, my mother thought coffee was bad for growing children. Gosh--did she reallv? Was tbie e matriarchy? You've indicated that it was in a way. Yea--well, she was the head of the family because my father was away 11 nearly half the time. Did she exact standards from you? Oh yes. I even got whipped when I was naughty. There was a cat-o 1 - nine-tails in the family that was used on occasion. I guess this was a period when enforcement was more family centered. Yes, but on the whole I don't think I gave very much trouble. I must have been a pretty horrible, little prig, I think, when I was a kid. I think, in retrospect. we're probably all somewhat like that--en uncut diamond, a diamond in the rough. reedy to be shaped bv time and effort and love and affection. I guess that's all part of the process. There was just the two of vou--two beys? Yes. It's unbelieveble--things that can happen. I laugh because I used to come home from school--a normal kid who had been through a few backyards and over some fences--and mother would greet me at the door and aav, "Don't walk on the floor!" Well. it apparently never occurred to her how we were going to qet in the house. This was her almost daily thinq--well, the floor was epotl&ss. You could eat off of it. She didn't want you to track mud into the house. Yes--we got to the point where we would suggest that maybe we should fly? It was her eenee of duty--her's was a Vermont background. Your mother had charge of the household--six months of the year anvwav, and it's not easy. 12 No. How about food? Did you eat most everything? Yes. There were fads in the household from time to time. My mother subscribed to Health Culture at one time. I think Elmer Lee was the edi­ tor, and he was even our family physician for a while. He thought it was sinful to put salt on eggs because "there's enough salt in an egg for a chicken. Why should a human being have to put salt on an egg?" There were a few, little things like that that were somewhat disturb­ ing to growing children. Su;e. The generalization, thet one confronts as one growe UJLOne likes ta shoot fyll pf holes aomet:1:me, and this might be one of them. Th1re is great variability in both the need and the demend for salt. Also there's habit. Yes. Where one draws the line isn't quite eo eimele. Did you have fun too-­ at home? Yee. Wps vour mother one who would play with you. or was she sort of removed and remote? She was a little remote. I think we did most of our playing with each other. I know my uncle, ! guess it was, gave us a telegraph set, and that kept us busy for ft long time telegraphing between rooms in the Morse code. 13 Was there a change in the atmosphere when your father came home? Was he approachable? Yes. He used to take us to the zoo and to the--well, we went to the museums without him. My brother and I really used to range all over New York City. We walked a lot. We almost lived in Central Park. We knew the local policeman. We knew the drivers on a lot of the delivery wagons, and they would take us to different parts of the city. They weren't as stuffy then as they are now. We'd find our way home then from wherever we wanted to be dropped. Even when we were living on East 90th Street we used to go up as far as Grant's Tomb very often and down to the Museum of Natural History on the west side, the Museum of Art--we were around there quite a bit too and without getting very much out of it, I think. That•e good--the sense of roamiryg. New York City was your oyster. Yee, and you could go all over the city really without being in any appreciable danger, ae far as we knew. I think that's true. and you did 99 to the museums. Yee. Was art part of it? A small part, I think. It wasn't something alien. No--we grew up with the Rembrandt pictures in the Altman Collection. We didn't know much about the Impressionists. That came later. 14 You had plenty to feed on though. Yes, and then too my mother insisted on our learning both German and French. She had come back--What is it, Pat. Thanks. Put it in the ice box. Leave the lab~l there. Well, my mother had been in Germany for a year and as we were growing up--I don't know when she started this, but there came a time when we had to speak German at the table. That was the rule. Of course we hated it, but we had to do it. We learned Garman aa a result. Then my mother got e governess, whom we didn't like very much, to take us out in the park a couple of times a week and talk French. We hated that too. We wanted to roam around on our own in the park and not have somebody talking French to us. We hated that, but we learned French, end it wasn't until much later that we really realized how wonderful a privi­ lege that wea. Right. Did she ever give vou any rationale as to whv she wanted you to learn German and French--iust a guidditv of hers, an interest of hers-­ that she thought YOU ought to learn. She admired what was going on in Germany at the time she had been there. That was before--long before Hitlerism of course, and before Prus­ sian expansionism too, I guess. Besides in South Germany the atmosphere was a little different anyhow, and it was just part of our parents• gener­ al realization that the more you knew the batter off you were. What time wee this enforced etudv of Gel'ITlan and French? When you were at the Ethical Culture School? 15 No, this was before that--I guess from about the time we were eight, or ten and it went on for three or four years probably. It was while we were still at home moat of the time, or else going to public school. Well, you owe here great debt, don't yoy? Yes, I certainly do. There's no question about it. She might even be pleaped to kngw that today we 1111id something about get- ting your first article published in Italian. Yes--well another thing that my father did. This was after I got my doctor's degree. It was quite apparent that if you wanted to get a good post here in the United States, you had to top a doctor's degree in chem­ istry off with a year in Europe because instruction in chemistry wee not particularly far advanced here at the time, and although we couldn't very well afford it my father said, "You go ahead. Whatever it costs we've got to meet the bill." I tried to keep my expenses down as much es possible--didn't cut any more of a splurge than I had to. He said, "You keep strict accounts of what it costs." I didn't know particularly why he wanted me to do that • When I got back, it had cost .---.... tm!!E about eight hundred and fifty dollars for the year--everything included--the trip across which was only fifty dollars going over. I had a whole cabin to myself one French Line cabin class boat during the off aeaeon--eleven and a half days until Le Havre-- marvelous! I lived in a boarding house in Zurich that was run by an Italian 16 whose wife was an Austrian. She did all the cooking herself, so I got very good food, and it didn't cost much. I learned Italian there because there were a lot of Italian engineering students there, and they gave me Italian lessons, and I gave them English lessons. Well, the reason my father wanted ma to keep a strict accounting was that although he was never in affluent circumstances, as soon as I had d<·, -t~s.:ir>1(, a,i;au:•',,!._, added it all up he wrote out a checkAand gave it to my brother who didn't go to Europe. My father wasn't going to give me any advantages that my brother didn't have. Not even the faintest fume of favoritism. No. That's marvelou,. Was there--put it this way; when your mother and father were together was there' different attitude in the house,' different feeling in the house, or no? No, I don't think so. My father was rather quiet, and his wants were simple. He liked a few special dishes which my mother cooked very skill­ fully and which were always very good. She waa very complacent about that. I think she tried to make him happy tao. That must have been--well, I don't know much about what being a traveling salesman wee in those years, but it couldn't have been a very happy one for him. Oh--it was a pretty strenuous life. He--I don't know just how old 17 ha was. I guess he must have been about sixty-seven, sixty-eight when he found that the life of a traveling sale9man was getting too much for him. I had been earning part of my way through college by selling Virginia Hams and Watergrcund Corn Meal around the city, to Hotels, to wholesale grocers, and sometimes even to small retail grocery shops. I usually took Friday afternoons off for that work while I was at ccllege. When my father re­ tired from traveling, he took that over and ran it as a kind of retirement business. After my father died, my mother even tried to keep it going for a little while, but she wasn't a business woman. It didn't go on for very long. One of the things I wondered about was whether you had any commercial ex­ periences at all. Oh, yes--a little. Necessity is the mother of invention. Well, my mother came from Virginia, and we had Waterground Corn Meal around the house all the time. I thought that selling Virginia Hams and Waterground Cnrn Meal was something that I could do. I used to make from ten to fifty dollars a week that way--just on one afternoon. That's pretty good. It was fairly profitable. My father always kept very strict books, and he wee used to double entry bookkeeping. If his accounts didn't balance by one cent, he'd spend hours and hours trying to find out whera the one cent had disap­ peared. I aaid one time, "Why don't you chip it in and call it square?" 18 That would not have been right apparently. Not only that. That's a standard--I know about double entry bookkeeping and the need for balancing. 9nd sooner Of later you run into his problem. Yes--to make a mistake of one cent apparently is a very serious matter. My brother died et the age of twenty-one, I guess, of endocarditis. He had a long, very distressing illness. My mother was really the practi­ cal nurse all the way through it. She bore the principal brunt of this illness. Then when my father was seventy-six, he got the same thing, though he had never had any heart trouble before, and he died of the same thing. My father is one of the oldest people on record ever to have bac­ terial endocarditis. As a general rule the family had been a healthy one, had it not? Yes--most of my mother•s--well, they all were not so terribly healthy. My mother lived until she was ninety-nine, end one of her sisters lived to be ninety-six. The others ell dropped off before that--some with men­ tal symptoms and some without. My father's brother, who was his closest relativo that I knew very well, I guess lived to be about seventy--I don't know what he died of. He was in Philadelphia. You beys had the normal •••• We had ell the children's sicknessee--chicken pox, measles, or German measles. I don't think we ever had real measles, but we had bronchitis 19 and plenty of sore throat. My brother hed rheumatic fever, end it was the sequelae of that, I guess, that ultimately gave him endocarditis. Were there doctors in the family? You mentioned one--Dr. Lee. No. All the doctors were outside the family. They were not members of the family. How about druggists, pharmeciets--did you know any? We never had any in the family. Ones with whom vou dealt as a family. You said that at eight you wanted to be a chemist. That was just a childish notion, I guess. I don't know what gave me the idea firet, but as I said, the only tangible thing that I could do was to mix talcum powder and cough medicine and various things of that sort end just see what happened. Nothing very interesting happened. It wasn't like the case of my own son who had a "Chemcraft" set at a very early age, and as he got more and more interested in them, they got more and more complex. You could do reel chemical experiments with them and really learn something. He gave magic shows with his Chemcraft end all that sort of thing, I never had any of that kind of advantage. I think it was mostly that I was very obstinate. Once I had an idea I stuck with it, and luckily it was an idea that I had some aptitude for. If I had decided to be a musician, it might not have turned out so well, or especially an artist. I suspect that it's the wise person who gives himself a sense of direction 20 without being more detailed than that and then lets life unfold. though he hps a prgdisposition to be excited by scientific things. Yes, but I never knew why I wanted to be a chemist until I began to study chemistry in my fourth year in high school actually. I Just stuck to it all the way through. That was what I was working toward. It took a long time for chemistry itself ta come along. As soon as I began work­ ing with it and on it, I knew that was where I belonged. There weren't any other alternativee that vou thought about? Yes--I was told, playing in one or two orcheatr■ a, that I could be a professional clarinetist, if I wanted to be. They thought I was good enough. But I didn't want to be a professional clarinetist. Playing the clarinet was only incidental and fun--the chief relaxation, really, that I had. Music is imgortant then, isn't it? Yes, it certainly is. It -was a complete change. Did yoy have a teacher? Yea. When I decided that--well, actually I would have liked to have played a string instrument. By the time I wanted to play something I'd heard enough concerts to know that the string instruments were terribly difficult and that if you didn't play like--who was it at the time; well, I've forgotten--people didn't want to listen to you. You just had to be very good, and I knew that if I stuck to science, I would never be able to practice enough to ever be able to do very much on a string instrument. 21 I always liked the clarinet the best next ta the strings. Another advantage that I realized even at the time waa that people were much less familiar with the clarinet, and sa they would put up with less than great virtuosity, ao I opted for the clarinet. l didn't know how much a clarinet would coat. There was ■ shop over on Park Avenue around the corner from where we lived. A French oboe make~ L..--.. c.:""'" ,1 opened this shop, and he had a coupJ.e of clarinets 11'\d bassoons and oboes in the window. 1 went around there one day and asked if I could work toward paying for a secondhand clarinet by working in the store a couple of afternoons a week. He said that he didn't have any job for anybody like that, but that there was a clarinet teacher right there in the stare at the time, "Talk to him." ,--, He was the first clarinetist of Del•y•s Theater orchestra. They '- used to have theater orchestras in those days. I talked to this clari­ netist, and he said, "Well, your father ought to be able to pay sixty dul­ lars for a new clarinet. Ask him. 11 I went and asked my father. and he was willing, and this man Heckert-­ Fred Heckert his name was--went down to Fischer's, the chief import agency-- ~\G L~j <: t they had the iguffe-y Agency. He weited until there was a new importation. Hackert knew Max Fischer very well, the old bearded Max Fischer, who was head of the wind instrument pert of the house. Heckert showed ma exactly how he picked out the best clarinet in the whole importation of about twenty. I got a beautiful instrument. Heckert said that he would give me lessons. He didn't charge very much--two dollars, 1 think, for an hour, or something like that. 1 took lessons from him far about three years, and then I began, really, to be 22 specializing in chemistry and working very hard up at Columbia, and I couldn't practice very much. Hackert was a very strict German. He fin­ ally said, "I'm wasting my time on you, and I won't give you any more lessons. You don't practice." I said, "I practice a little, but playing the clarinet is not what I'm going to make my living on. I'm most interested in chemistry, and that's what I have to spend my time on." "I can't help it. You're wasting my time." He threw me over. That was the end of my lessons for about fifteen years. It is a whole new world--music is. Yes. I found it a kind of different level, different sense of concentration, different values. Yes-you lose yourself completely. I think it gives your other brain centers a chance to rest a bit. I~'s an eddv tog in a senae--away from whatever tensionp one cgnfrgnts. No matter how tired I would be~-if I would practice for a half hour, or play for a half hour, it would set me up wonderfully. I can understand that. When it came to get an A clarinet--my father was willing. The price had gone up to ninety dollars by that time. I went down, end I knew how 23 to pick out the best one in the shipment, and I got an even better A clar­ inet than the B flat one. 1t 1 s a marvelous instrument. Whan I had them both looked over a few yeare ago, the man who is down at fischer 1 s now said, "You never see wood like that any more~" They have marvelous parts fer the clarinets in orchestral works. Well, until I got married I played a lot in orchestree--the Columbia Orchestra for one. There were three of us up there--three clarinets. I ~-:PfOJ,y was the second clarinet. Another fellow./f\was the third clarinet. We looked around for thing~ to play, and there wasn't very much. We began writing our own clarinet trios, and we played them at a couple of Music ._Q~et C. T"'-tli:t:_, Department student concerts. The first clarinetist really went on in mu- .II\ sic. He's very good, and he wrote good stuff. He'e still playing. He was the director of the Memphis, Tennessee, Academy of Music for very many yeers--played in the Memphis Symphony, still plays base clarinet now in the Memphis Symphony. I see him every once in a while at Alumni meetings. After I got married, playing in orchestras took me away from home too much so I began playing chamber music which in the end is much more satisfying. Isn't it? Do you play? Somebody threw a baritone horn at me one day--I was what; seventh grade, sixth grade I guess it was. They said 1 "You give us a lot of trouble with your voice because you're alwavs noisy. You have a set of lungs--here." +a.IE:. Thereby hangs a . Well. the parts for baritone horn are just marvel- 24 ous--just marvelous parts! It kept me out of mischief. introduced me to a whole lot of things thet I would not have known perheps so much ;bout at all. Do you still play? Not so much. though I heve a daughter who is a baritone horn player. Another plays trombone as a matter of fact. It must be pretty awful to have two braes--three brass instruments in one house. It's very quiet reall¥, though tbev have a lot of jov oyt of it at school. Well. let me turn this ta;e over. Somewherg in 911 these notes--xou men­ tioned Percival Chubb. Yes. Thinking about the Ethic9l C4lture School tberg was no question @boyt vour going, although--well 1 there was a tuition for tha school. It was a private school. Yee--well, I had a partial scholarship. My parents paid part of the tuition all the way through, from the eighth grade all the way through high school. Just what fraction they paid I don't know. There's a record [Ethical Cultur! School Record (N.Y.C, 1 Max 14. 1916)1 published in 1916--a record of graduates which indicated that voy had been a scholarship student, uut I didn't know for how lon9. It was ell the wa¥ throu9h then. 25 Aa far as I knew--! don't think my parents ever paid the full tui- ticn. Where was it--669 Madieon Avenue. No--48 East 58th Street. Yes--well, I started et the old Workingman's School on West 54th Street, I guess it was. It was in an old building, and that's where I tock my eighth grade work. They were still there. Then they started building the new building over on Central Park West, and while that was going up they moved the high school over to East 58th Street. Yea. There's e fellow in the class ehead of vou--1 think the class ahead gf ¥PH w9s the first official cless to gxaduate. · ,K.)aber- Yes. It had people like De epins Taylor, Florence Wolff Clai~s. !\ Alexander Holtzoff. Yes, we used to call him "Alex Hand the Hot Stuff." He developed vary strangely afterwards. A Judge of the Circuit Court of Apppaj.s for manv years. Yes, a very conservative one too. Yea--well. experience ia a etrange thing. I'm not sure, but there was listed in the class ahead of vou a Gertrude R. Stein. Yes. Was that the Gertrude Stein? 26 I didn't think so, but I did wonder. Your own class had Lee Simonson. Yee, Lee Simonson was in my class. Lee and I didn't get along too well together. He was alweye rather a conceited sort of pereon--it seemed to me. I guess he was lees inhibited than I was. Creative. Yes--he certainly was a very talented artist. He port gf had peaks--ups and downs--that excitement in Jhe human psyche is alwavs exciting. He was rather vocal and talkative. I guess I was rather quiet and didn't say very much. You had a Hanf¥ Kelly for science, He's worth a word. Yes--Henry A. Kelly. He even took me as assistant director of a sum­ mer camp he ran. We took eight o~ ten boys on first, and then we had girls far another three weeks afterwards. That worked out very well. I learned a lot of woodcraft from him, a love af tramping in the mountains. I even took some Waterground Corn Meal along with me and tried to make some corn bread, but I put the baking powder in first and then scalded the whole thing instead of scalding the meal first and then putting the baking pow­ der in. I wandered why the darn stuff didn't rise. Kelly I guess gave the school whatever it hed in terms of science. 27 Yes--well, he was the biology teacher. I don't think he ever attempted to teach chemistry, or physics. There is an Augustus Klock. He came later. William E. Stark was the Principal of the high school, and he taught physics and chemistry. I didn't have any physics, or chem­ istry until he came along in my third year of high school. I had him in both chemistry and physics. There ip a fellow named Guy F. Welle in physics. Wells? Wells. I never had him. Did you have Davids. Muzzey for History, or for Greek? For History. I didn't take Greek. Latin? Yes, I took Latin all four years. Muzzey taught it part of the time, ,,.-., and my class teacher--Susan Bralley Franklin taught it part of the time '--" too. How did you like Latin? Oh, I liked it. It was interesting. It helped me with--well reed­ ing Spanish. I can read Spanish and Portuguese without too much trouble, 28 eepecially if it's acientific. Latin helped me in french--going on with French later, and certainly with Italian too. It ie the root for a lot qf things. Yea--I never regretted my four years of Latin. Did vou take German there too? Yea, I took Germen. With Miss Freda van Unwerth? Vea, Frede van Unwerth--I wonder whether she was the one. We used to have lots of fun at her expense. I don't think it was van Unwerth. Amelia Wohlfarth. Yea, I think it was Hiss Wohlfarth who had very picturesque expres­ sion ■• One sunny day--thia was on 58th Streat--■ bird flew by, and &he illtv--ew saw the shadow. She looked around the class end said, "Who ~up? Who -+hr,.:.,,.:, ···-y---, :a;. up?" It was either van Unwerth, or Wohlfarth who asked if I wished to be ~ called "Michel•• Ni9wel or Moik." 1 ,F a;t-~ Then we had a Mr.~, I think, who taught French, and I was guilty of throwing buckshot under the folding doors into his claaa one day and got called up on the carpet for that. The school wasn't a very large echool--was it? No. 29 Your clasg, I think. had seven membera--a small school. When I was in my first year there they plunked a young fellow down -~Jew~~n next to me with a terrific English accent, "This is a.e-ellen Lloyd. Take good care of him." We got to be very good friends, and our friendship lasted a long time until he died in the 1930'e, I guess. This is where circumstances conditioned life. He waa--his chief interests ware literary. Ha wrote very good verse. I looked through. copy of the "Inklings". This wea a publication for the school. Yau didn't write for "Inklings", did you? I must have written one or two small things for it--nothing very much. I didn't find them. I'm not saying that they're not there. I don't remember whether I actually had anything published in it, or not. It seems to me that I must have written one or two things. It was published gyarterlv--three times a year, I think. and the New York Public Library hae a broken edition, so that it's iuat possible that your pieces were in the copies not available to me at the librar~. It came out rather irregularly I think. Frank A. Manny was Superintendent. Frank A. Manny--well, we never had very much to do with the superin- 30 tendent unless he happened to teach us a course, or something like that. I never had any couraea with Manny. When you say you were called up on the carpet for throwing buckshot •••• That was before his time I think, er at East 58th Street when I was still in the first year of the high school. He might have been appointed then. I don't remember who it was that gave me this lecture as a result of that prank. Dg you remember mathematical Did Stark handle mathematics? No, Matilda Auerbach handled mathematics. She was my mathematics teacher and really a remarkably good one. w,, •be? Sha was marvelous. She was pretty well hated throughout the school because she didn't have much use for the people who weren't good in mathe­ matics. She hag• kind of contempt tor the beck benchera. She was quite strict and really an extremely good teacher. It wasn't until I took calculus up at Columbia with--I haven't thought about his name for a long time, but his course was the first time that I got as good teaching in mathematics after I left high school. Here's e liat af thp professor• in the Mathematics Dap■ rtlll■nt at Columbit• Casaiua J. Keyser. He was a marvelous teacher. I had J. Howard Van Amringe in advanced algebra. He was the Dean of Columbia College, quite 31 old and not a bad teacher, but not distinguished. His stock phrase al­ ways used to be if someone came along who hadn't done their homework and would say that thay didn't have time to do it, "What do you mean you didn't have time? There are twenty-four hours in a day. You had them all, didn't you?" What was the distinguishing thing about Miss Auerbach? A stickler for work done too? She loaded ua down with lots of problems every evening, problems which had to be done by the next day, or the next lesson, and they were often very tough. That's the challenge. She wee a martinet, but she alway• explained thing• very well and very clearly. I got along with her very well in her courses. We even had trigonometry at high achool--I think it was the only high school that had ever given a course in trigonometry, a beautiful course. When the time came to go to cgllege 1 was any other college thought about? Whv Columbia? It was the cheapest, I guess. It would have caused more difficulties to go away from home. The simplest thing was to live at home which was a mistake, I think. I ahould have gone away, but I didn't. There wasn't any question about your qualifying at Columbia in terms of the entrance reguiremente. 32 No, and I think they took everybody at that time who passed hia en­ trance examination. I had no difficulty about that. I lived at home all through college and all through my graduate work at Columbia too which was an awful mistake. Wby--did you feel the sense of no freedom, or what? No--I just didn't know any better. I think I would have been better prepared for an independent life, if I hadn't stayed at home so long. I was too much under the domination, I think, of my family. Thia is nq rationllle 1 but there eomee a point where there just isn't any way to communicate what it is one feels and eensee without--vou know, the possibility of hurting someone. Well, that didn't coma until after I was married. It must have enabled you to concentrate pretty well on the college work, chemistry. Oh, yea. I mean, I never had any difficulties at home. I present to you a list of who was there at Columbia in the Chemistry De­ partment. and perhaps you can give some insight into the department, what was in the air. the quality of these people and particularly two of them, Dr. r1oyd J. Metzger and Professor Marston T. Bggeft with whom you wrote soma early aapers, but what of the chemistry faculty as a whole? I think on the whole they were es good a chemistry faculty as was available st the time which wasn't saying too much. You really could not get a very good chemical education here in the United States at that time 33 and--well, Charles F. Chandle= was the Head of the Department. I to8k his course in Industrial Chemistry and his course in Elementary Chemistry, and both of them were mostly a collection of anecdotes of his own personal ex­ perience. They were both marvelous courses because they taught you that chemistry wee not just a science off by itself. It had a relation to al­ most everything that was going on in the world and I think that was the greatest value of his courses. Chandler would tell you stories of how the best thing he ever did was to do a job for nothing for New York City. That waa back in the days when they were having kerosene explosions all over the city, and because he was a chemist--he was an instructor, something like that, a young fellow--he was asked if he would try to find out what the trouble was. He did such a good job finding out what the trouble wes and caused so much trouble for the oil company that they appointed him a consultant at a very high salary immediately afterwards, and ao he said, "The best thing I ever did was to do a job for nothing for the city." Chandler was full of stories like that in every conceivable direction. Did he also take charge of the laboratory work that you did? No--there was no lab work. This man--I don't think it was Edmund H. Miller who had gone abroad when I was a freshman. Hal Truman Beans was the man who influenced me most that first year at Columbia. He isn't on this list et all. He may be on this one--1907-1908. Where is page 54--yee, here he is, He's listed es a tutor in analy­ tical chemistry, in qualitative. Well, the professor--I guess it must 34 have been Miller who went abroad for a year. No, it wea James S. C. Wells who was actually doing the teaching in analytical chemistry. Welle went abroad for a year and left strict instructions that Beane was to teach qualitative analysis according to the old Cook Book methods. The ionic theory had just been promulgated at that time, and Beans had reed it and was terribly excited about it. He made up his mind that he was going to teach analytical qualitative analysis the way he wanted to and not the way that old fuddy-duddy did it. We had a marvelous course in qualitative analysis that wee based on the ionic theory. It really was an extremely exciting thing. Thet•e where I really began to love chemistry, feel my way into it. Beans and I got to be very good friends. He made me an assistant for the summer session and got ma a job with Irving Langmuir down at Stevens Institute. That was very stimulating. I used to come home on the ferry with Langmuir at night, and he'd tell me soma of the things he was interested in. That was qualitative analysis. That's how I got through Columbia College in three years. I got eleven points for that one course. I waa in the laboratory every afternoon. Then I started analytical chemistry when -----i----- with Metzger. Miller I never knew, and Wells, ~ he came back, I didn't have anything to do with him. He put Beans up on charges for discbeying his instructions, and the matter was taken to the President of the Univer­ sity who was Nicholas Murray Butler at the time. Butler sided with Beans. He said, "We're going to have the most modern instruction possible at Columbia whether the heeds of the departments approve of it, or not.• Beens made the subject exciting. 35 Yes, he certainly did. Metzger then--Metzger offered me a fellow­ ship, if I would stay in analytical chemistry. By that time I knew that I wanted to be an organic chemist and not an analytical chemist, eo I turned down the fellowship end went on in organic chemistry. How did you come by this decision on organic chemistry? Well, organic chemistry was just something that you could work your own personality on. It was so flexible that you could plan things, and maybe they'd come out and maybe they wouldn't. Organic chemistry just at­ tracted me more than any other branch of chemistry did. Bogert was the Professor of Organic Chemistry and John M. Nelson wee hie chief instructor--he 1 s not down on this list. He must have come in the next years. Well, Nalson--1 had some ideas by that time, by the ti.Ille I got through. Bogert was really a remarkable teacher of organic chemis­ try. I learned a lat of organic chemiatry from him. He would write two completely different things on the board, and then you'd have to synthe­ size the second one from the first, and often it was e frightful job. He just took any two that he happened to think of. That was really a wonder­ ful exercise. Although Bogert was a very goad teacher, he was terrible when it came to research work. The head of tha Chemistry Department, Chandler, retired. There was en Englishman--Kendell, I think, and he was appointed head of the department. He waa half crazy and didn't laat very long. They made Bogart acting heed of tha Department of Chemietry while I was doing re­ search with him, and he used to come in in the morning and lock himself in hie office. He would go out to lunch and come beck and lock himself in again in the afternoon. Most of us never saw him for a week or ten 36 days at a time. We just had to struggle on without any help until Nelson came along--"Pop" Nelson everybody called him. He was wonderful with everybody. He always had plenty cf time. He was a very quiet, soft spoken person who always had plenty cf time to listen and plenty of time to help you. He was marvelous! We really did our graduate work more with Nelson than we did with Bogert, though Bogert essj.gned the problem. In a way Bogert was very wise, l think. I wanted to work on organic /) phospho3teus compounds. They struck my fancy for some unknown reason, and they were horrible things to work with because a lot of them ignited spontaneously in the air. Bogert had a few of them in the chemical muse­ um which he gave me, and we planned a few sort of half-baked experiments with them. Nothing turned out, and he knew very well that nothing would turn out. He was wise enough to let me have my fling with what I wanted to do, and then after a few months of completely frustrating results he said, "Well, I think you'd better take a quinazolone problem." That was his stock, his field in which you could work out everything on paper, and everything always worked. Everything gave you beautiful ~- cryataline compounds, and if you had forty compounds, you got a Ph.D., pro- " vided you satisfied the other professors in the Department. Well, he set me to work on something that he thought was going to be a L.!seful dye. One of his former Ph.D. 1 s had made a phthalone dye with phthalic acid and one of these quinazolonee. The quinoline analog had been a moderately good, yellow dye, so Bogert thought that this ought to be pretty good in this series too. It was ell analogy work. You just figured out the reac­ tions, and they always worked in this aeries because they had always worked in the quinoline series. I worked on quinazolone phthalone and found that as I purified it, 37 it got paler and paler until it had practically no color at all, Well, Bogert lost interest in it then. I had found that if you treated quina­ zolone phthalone with bromine it suddenly decolorized completely, I looked up what had happened with quinoline phthalone, and nobody had ever treated that one with bromine, so that there was no clue as to what hap­ pened. I thought, "Thie is real interesting, I'll treck that down and aee what really happens." I spent a year doing that, and Bogert, of course, had shut himself into his office and only came around once every two weeks, or so and saw that I was still working and that wae almost enough, He didn't say much about it. When it came to write up my dissertation, I only had twenty new compounds instead of forty, and although I had solved the problem of what happened when you split quinazolone phthalone with bromine, that didn't inter•st him particularly. I had only twenty new compounds-­ half as many as you were supposed to have, Eventually--! suppose Nelson urged him to let me by anyhow--he accepted my thesis, and I got my doc­ tor's degree. Yoy know leter on--much later on. there is a group established to do honor to Bgge;t end he's de1cribad as a brilliant man. 8 wittv man. He was--he was a very charming person and a very good teacher of organic chemistry, but he got sidetracked. He manufactured Ph.D. 1 s that way by getting off on a sidetrack where everything you did worked. Well, that's one way of doing it, and I suppose it's no worse than any other, especially if you consider the state of organic chemistry at that time in this country. I don'l think that there were many people who were do­ ing better work than that here--very few. 36 ~ When I was a boy we hed a physician, an old man, Samuel J. Meltzer. He was a Russian who had come to the United State&. He'd studied medi­ cine, I guess, in Europe, and I remember him first because he had a very large, soft head. He used to poke his ear into my chest and listen when I was six, or seven, or eight. He pulled me through typhoid fever. He was a wonderful family physician, but he was also very much of a physiolo­ gist. He kept doing a little research all the time which was something that my family and I didn't know anything about. When the Rockefeller Institute was started, Meltzer was made head of their Department of Physi­ ology--our practicing physician, so when I was about to get my Ph.D., my parents said, "Why don't you go down and talk to Dr. Meltzer and see what you ought to do next." I wasn't particularly keen about doing that. I thought I ought to try to get a job somewhere, but I finally allowed myself to be persuaded. I went down to see Dr. Meltzer who remembered me from many years before and who remembered my parents. He said, "I don't think you ought to go into scier.ce. Science is no profession for a poor man's son." I think he was right. I think if he could have frightened me off, I really would have had no real vocation for science. I think that was his idea; that if you can scare anybody away from science, he has no busi­ ness in science, but if you can't scare him away from it, then he's for it. I said, "I want to be a chemist." I did thank him for his advice, but I told him that I was going to go into chemistry anyhow. He said, "I don't know any chemistry. I'm a physiologist. I'll turn you over to the chemists here." Well, Phoebus A. T. Levene and Walter Jacobs were the chemists there J>.D. ~ andftVan Slyke. 1 happened to ba there fairly late in the afternoon, and 39 Meltzer called tham up, and they were just having tea, so I went around and had taa with them. I thought that I would like to go to work with Emil Fischer in Ber- lin. Levene had worked with Fischer. Jacobs had worked with Fischer, jj-',~':li'l) and Van Slyke had worked with Fischer. There was a German-America13~wh0· was a sort of a laboratory teaching assistant up at Columbia, and he was the one, I think, who firat told me, "You have to go to Europe, if you want to get finished off in chemiatry. You can't get a very good posi­ tion here without study in Europe. You can't really learn about diffi­ cult things in chemistry here in America." Well, I made up my mind that I wanted to go to Europe and study for a year. My father said that he would put up the money for the year of study abroad, so I went down to get advice from the Rockefeller people. Jacobs and Lavene said that Fischer wee getting old, that most of the contacts were with Fischer's assistants and not actually with Fischer any more, and that they wouldn't advise me to go study for a year with Fischer. I should go to some younger chemist like Richard Willstatter who was doing terribly difficult and interesting things, working on chlorophyll and on enzymes. I should go to Willstatter instead, so I wrote to Willstetter, and he agreed to take me at the Eidgenossische Technische Hochschule in Zurich. I went over there fer a year, and that's when I really began to learn how to deal with difficult things in chem­ istry. I was wondering about the laboratory work at Columbia, What sort gf fa- cilitv did VDU have? They had a good organic chemistry laboratory. We did lots of 40 experiments. We made quinoline out of nitrobenzene, and eoma of them had axploaiana as e result. We did all the standard preparations, made lots of things--eome easy and some difficult. It was a good course in stan­ dard, routine organic chemistry. Was it anything beyond the Cook Book approach? Not really--well, Bogert, yea. You had to think in Bogert'e course and Nelson's too. Nelson gave a very good advanced organic course. They would give you very difficult problems. Like I said, Bogert would write two things that were completely unrelated on the board, and you'd have to think how to go from one to the other. I think the instruction was vary good. Morgsn--J. Livingston Rutgers Morgan gave a fairly good course in the phyaical chemistry of the time which was not really very profound, but it was a good course and adequate for what was known at the time, I think. There was nothing very startling about it. Beans was the m■n who had the real ideas in physical chemistry but that was relatively simple too--the ionic theory. I think it wee W. C. Bottger's book on ione that had fired Beans. [Prirycielga of Qualitative Analysis from the standpoint cf the theory of elactrolytic dissociation and law of mess action (Blakie­ ton, 1906)]. These are all old chemists long since dead. Sut this i1 your 1t9rt. Well, anyhow, Levene, Jacobs, and Ven Slyke said that I should go to Willstetter, and so I went over and worked with Willstatter. I said, "I'd like to work on chlorophyll." 41 Willstatter said, "Well, then you've got to stay two years. It'll take you a year to learn methods, and then you can do some research for a year." I said that I didn't think my father could afford to keep me over there for two years, that it had better be some other problem then. Will­ statter had a man who had just succeeded in making cyclo-octatetraene,, the next higher analog to benzene--8 carbons and four double bonds. It had proved to be a very difficult problem with a very elusive substance. It threw bonds across the ring in five minutes if you didn't look out and did all sorts of unpleasant thinga. Willstatter wanted to know more about it. They were sure that they had it, but they hadn't studied it enough, so would I do that? I thought that was as good a way to learn how to handle difficult things as any, so I said that I would do it. Willstat­ ter said, "It's going to be a very expensive investigation because the starting material costs five hundred dollars." This was five hundred dollars worth of en alkaloid that you had to break down and make this ring. I told him that I couldn't handle anything very expensive because my father wanted me to keep my expenses down, and he said, "Well, I'll buy one thing, and you buy the next." He was wonderful that way. He paid for the five hundred dollars worth of starting material. I had to use vast quantities of silver ni­ trate to get rid of the nitrogens in this alkaloid and demethylate them. Whenever it wee my turn--I had to buy something like acetic acid, or sul­ furic acid, and whenever it was his turn it was the silver nitrate, or the expensive things. That coyldn't be b•ttpr, could itl 42 Yes, it was really wonderful. He's I distinguished looking man. That's note very good picture of him. He was a much kindlier look­ ing person than that. The first day I was working in the laboratory he gave me some model material to work with juet to get my hand in so that I wouldn't ruin any very expensive stuff. I was doing a steam diatille­ tion and watching it, and all of a sudden crystals formed in the stuff. The whole thing set nearly solid while I was running steam through. I thought, "Whet the dickens is this?!" I didn't hear Willstatter coming into the laboratory, and all of a sudden an arm shot past my head and a finger pointed at the material and he hissed in my ear, "Was ist des? Was ist das?" I was so scared that I couldn't answer. He asked me if I wanted him to speak English, or German. His En­ glish was just terrible at that time, so I knew I wouldn't learn nearly aa much as I would if he epoke German, so I said, "German, please." Then I really hed to begin to learn hew to think in German because he'd ask rapid-fire questions in German, and you'd have to answer them. He had about twenty people working with him, but in spite of that he was always there in the laboratory with you twice a day anyhow. Accessible. Yes--I mean he came around to where you were working twice a day to see what you were doing which was very different from Bogert. Yes. The first five items on this bibliography of yours are a consequence 43 of your Columbia experience and the Zurich experience. Yes. How did tho•e problems evolve with Metzger? I worked for honors--! got honor• in analytical chemistry. I got honors in qualitative analysis too, but that didn't result in a publica­ tion. I just had to do a rare earth unknown to get honors in qualitative "'JS analysis, but Metzger--this ~ ,'\ a very interesting problem. Metzger said ,,...,..--·. ._ that he didn't believe the formula that was given for .:tt.. sodium -.uranate. It was in all the chemical books. The method of analyzing for uranium resulted in this sodium1 ·uranate being farmed. You weighed it. It had a crazy compoeition. Metzger said that he didn't believe the formula, "Let's find out if it's right, or not." We had ta analyze it for sodium and uranium, and it was the Pateaa•s method that resulted in this thing. t '-'-" Yau ¢rested uranium compounds with sodium hydroxide and got a yellow precipitate. Well, PeteQ.a published his method back in 1815, or 1817. molecular weight of eight at that time. ,,,-\ That--- They considered oxygen as having a f;asa: threw everything else off. The formula that Paterta '-·· wrote had come right down through even though they had changed all the other formulas to make oxygen 16. That was the only thing that was wrong with this formula. Once you had mod­ ernized the formula, it came out ell right in accordance with the actual chemical composition, so we'streightened out the analytical chemical books that way. ["On the nature of certain sodium-uranium compounds" 31 Journal of the American Chemical Society 1040. (1909)]. Metzger had published same work with other people on cerium, He 44 used cerium oxide as an oxidizing agent. We did a small piece of work on that and ser.t it to the Journal of the American Chemical Society. Old men Noyes, William A. Noyes, was pereor.ally the editor of the journal at that time, and he sent our article back. He said that he didn't think that we knew how to standardize the potassium permanganate that we used. Well, Metzger had been sitting on my neck the whole time, and he knew that the potassium permanganate had been standardized properly. Metzger went straight up in the air. He sat down end wrote Noyes saying, "Dear Professor Noyes. We do know how to standardize potassium permanganate. Either you will take this paper as it is written, or else I shall send it to the Zeitschrift fur Analvtische Chemie with a note explaining why I am sending it to them." Well, Noyes took the article. ["The volumetric determination of cerium in cerite and monazite" 32 Journal of the Amefican Chemical 59- cietv 642 (1910)]. Metzger in comparison to Bogert was pretty much of a vounaster too. Yes, he was young. He then went into industry and became President, I think, of the Air Reduction Company. He was working as a consultant for the Coca Cola Company at the time. We had big jugs of Coca Cola syrup in the laboratory all the time. The Coca Cola people were being sued by the government for putting dope in Coca Cola. Apparently there was so little dope that nobody could ever feel the effects of it. I think they took it out afterwards. It was only in the name. They never had more than one coca leaf per thou­ sand tons, or something like that. Anyhow the amount was so little that you didn't get any of the effects that the South American aborigines got 45 from chewing coca. Waa--were vou encou.aged toward research, or putting vour wares in indus- Well, I think at Columbia most of the graduates went into industry. I wasn't particularly interested in that. When I was in Zurich, I wrote letters to every American university asking to be appointed instructor in organic chemistry. I got letters from almost all of them turning me down. The thing that hurt most was that the various American universities put two cent stamps on their replies. The Swiss assessed a double penalty by the time these replies reached me over there, so that every time I got turned down, I had to pay six cents for the privilege. Of knowing. Yea. Eventually there were two positive nibbles. One was from the University of Illinois. They definitely appointed me en instructor in organic chemistry. I accepted, and I was on my way back. I had been in­ tending to travel through Germany back to France and sail home on another cabin liner of the French line. I suddenly got a cable from my father to this effect; that the Rockefeller Institute will appoint you chemist in some new work that Jacobs is going to do, if you come home right away and are satisfactory to Dr. Simon Flexnar, tha Director. You couldn't be appointed in those days without a personal interview with Dr. rlexnar. -¥- I cut short my trip and came home on the "Prov_-nce" I\ , cabin class one .f1t,ec:-dasr -::nbiR boat, and got back in time. The funny thing was thmt getting into the train at Paris on the way to Le Havre I just got into a compartment at random, and it wae full of 46 people from the University of Illinois and their wives. I got the low down on the University of Illinois from them, and that made me more anx­ ious to take the Rockefeller job to do straight research than I would have been otherwise, probably. I thought that I'd like to teach organic chemis­ try and do some research problems on my own. I hed some rather vague ideas as to what I wanted to work on though. Well, I passed muster with Dr. Flexner and was appointed to the Rockefeller Institute. That started everything. Beck in Columbia when vou had pn essistantahip during the summer session, did that also involve some teaching, working with students? Oh yes. You'd had this then. Oh yea, I liked it. Wes this work in thp laboratory? Entirely in the laboretory. I don't think I even went to the lec­ tures. I supervised the students in the laboratory. There is this other summer experience that you'd had at Stevens Insti­ tura. How did that come about? That was also a course in qualitative analysis. You took thig as 9 student? No, somebody asked Beans to recommend a student assistant for the six weeks course there in qualitative analysis, and he recommended me, 47 so that I had two jobs that one summer. They didn't overlap at ell. The timing wee totally different, and I got fifty dollars for each six weeks course. No, the course at Stevens wasn't six weeks. It was only three, or four weeks long. A supplementary term. A supplementary term of three or four weeks. They paid the same as Columbia did, I think. Waa Langmuir there? He wae teaching the course in qualitative analysis. I don't think he was connected with Stevens otherwise. He was just a summer school teacher there, and he had big ideas then too, a very stimulating person. Yes--I only know him through hie--well. I guess it's hie •en down at the Communicable Diseeae Center. I don't think that•e his son. Some relation. I don't know. Maybe it is his son, but I don't think so though. How much insight into chemistry do you pick up from three weeks or four weeks with Langmuir? Did you get some a9nse of the size and scape af this man? Yee-well, I didn't get to know him very wall, but he waa an ex­ tremely strict teacher and vary unpopular with the students because ha insisted en such high standards that they didn't like it. Then too, he 48 was pretty much e slave driver. It was a very hot summer, and he was against letting them off on the hottest days, but the administration there finally insisted on it. There were half a dozen days when it would have been almost impossible to teach, I guess. There was no air conditioning, of course. It was a pretty grim time. How was he with his aaQistant? Well, we got along all right. Then, as I say, he used to talk about his dreams and the things that he'd like to do as we were walking down to the ferry from the laboratory. That was very interesting. You could see that he had his mind on other things--research projects and that this teaching was just a kind of bread and butter matter in which he wasn't really interested. He did it well for the people who were good, but for the ones who had trouble he didn't have any patience, really, with them. How did you view this comparatively--Beans aside--with the Columbia con­ tingent? Well, Beans was a much more approachable, genial sort of person. He was a very slow speaker. I think that even the engineering students who took qualitative analysis could understand Beans, although I had to do a lot of tutoring of the engineering students. They found the ionic theory very difficult to take. They weren't used to theory. They ap­ proved more af "Cook Bookery", I think. from what you've indicated. P;ofesscf b@ngmui; contributed both. He could be the strict teacher and also wap imaginative in projecting his interests. 49 Yes, but that was eomsthing that he favored me with when he was not teaching. When he was teaching, he was strictly tending to business, to the matter in hand, end inaiating on perfection and high standards that he eat for himself. Did you have fellow atydante in the Chemistry Department at Columbia from whom ¥OU learned not. littlp? Well, I had every good friend who was doing research there at the same time that I wee--Louis E. Wise. We got to ba very goad friends, and Louie was a much more unselfish sort of person than I was. Because I went abroad his parents wanted him also to go. I had persuaded them at least that one had to study abroad, if one wanted to get ahead here in the United States in chemistry. Louis refused to allow his parents to make the sacrifice, and his career really suffered very much as a re­ sult of that. He was a much more dutiful son than I was. I was willing to accept anything from my parents even if accepting made it difficult for them. Louis is doing very well too, in a way. His first job was es an instructor in organic chemistry at tha University of Missouri. That was a pretty arduous and unpleasant thing, and he ultimately-he went to Illinois and then ultimately to the Institute of Paper Chemistry in Ap­ pleton, Wisconsin, where ha became an authority on paper and the poly­ saccharides of wood. He's built up a reputation for himself, but it was a long, herd road. If he'd had a year abroad, I'm sure that he would have gotten ahead very much faster too, got more congenial positions anyhow. Getting ahead didn't neceaaarily mean that you were making more 50 money. I started at twelve hundred dollars at the Rockefeller Institute, but I was extremely happy there doing the kind of thing I wanted most to do. When I got married in 1916, they raised me from two thousand to twen­ ty four hundred dollars. Let me get another tape. I want to go back to Columbia for a brief vis- it. I made a comment that es a 1tudent I wonde;ed what, if anything, you picked up from your fellow classmates. You indicated the one fellow with whom you were quite close, but did you eat together as a group? No. Did you learn from one another? No. That's interepting. Even in graduate school? I had very little contact with the other people actually. That was,, tk,r1.t( ) because I !Male I didn't live there with them. I lived at home. Now I understand the misgivings. What about the library? Did you do much work in the library? Wat there much historical research in this sense, reading the papers of the past? Very little of that until--well, I started doing abstracting for Chemical Abstracts when I was a graduate student. One of the people who wee taking a special course--T. T. Gray I think his name was--waa in the petroleum industry, and he was doing abstracting, and he said, "That•a interesting. You have to read a lot of papers. Would you like to do some? I can get you some abstracting." 51 I started abstracting for Chemical Abstracts end carried that through until a year or two after I was married. Then that began to get rather burdensome. I had one abstract that nearly broke up my marriage because it took so long. It was the longest abstract that had ever been published up to that time. It was an abstract of a hundred page paper. Well--vou know, we talked about chemistry at Columbia. As a graduate student were there oral examinations? They had an oral. final exam. They didn't have qualifying examina­ tions. You just couldn't be accepted as a student if you hadn't passed your courses, and any of the professors had the right to be at the orel examination. You were not only examined on your thesis, but you were examined on the various subjects that y~u had studied. Morgan, who was the Professor of Physical Chemistry, saw Louie and me boning up for our final examination in the library one day, and he said, "Why are you tak­ ing this so hard? I'm net going to ask you any questions." We didn't believe him. We kept on studying physical chemistry too. The only person who really tried to sting us in the oral examina­ tion was the Professor of Electrochemistry whose courses we hadn't taken, and he just wanted to show us that we should have taken his courses, but we knew that even if we failed to answer what he asked us, they wouldn't flunk us, so it didn't matter too much--just a little disagreeable for the few minutes. Sherman was another one of the very good people up there--Henry C. Shermen--he was really Professor of Biochemistry, but he was interested mostly in problems of nutrition. He end his people did some of the early work on enzymes. E. C. Kendall, who ultimately got the Nobel Prize for 52 his work on steroids, was one of his students. I think by and large it was as good a faculty as yoy could find. Yes, I think so. I think that if I hadn't thought that I was get­ ting a good basic knowledge, I don't think I would have stayed there even then because I'd had some pretty poor teaching in the college. I didn't get along very well with the English instructor who wanted ma to write huge volumes of stuff that I just wasn't interested in, and the professor at the head of the English Department was not extremely inter­ esting. Next to Chubb, I thought the English Department was a pretty bad letdown. Mathematics was not partic~larly good until I got Keyser. In Philosophy Frederick J E. Woodbridge was the professor, and his lec­ tures were interesting, but the sectional work with the instructors was just so boring that you could hardly stand it--discussion of problems of logic. I suppose I should have been interested in it, but it was pre­ sented in such a dull way that I just hated it. I've never been a philo­ sopher. History was very badly taught too. Byrgese--did vou have him? I don't think I had him at all. Well. after Muzzey •••• The general lectures were fairly good, but not very exciting. The section work was so dull and uninteresting. You'd also had!•••• 53 Yes, I had had a lot of history, and most of what it was was a re­ hash in lees interesting ways of what I'd had before. I took Advanced German, and that was of some interest. Those were good courses. I had Calvin Thomas and he was a very absent minded per­ son--he shut himself out of the classroom one morning. He took hold of the deer, closed it, and didn't realize that he was on the outside in­ stead of the inside. He was an interesting person, and in the Advanced German course they made you write a thesis at the end of the year. There was a whole long list of twenty topics. One of them was "Goethe as a Scientist". I chose that topic, and I hed a terrible time with the pro­ fessor because he said that there wasn't enough material to write a the­ sis en. I said, "I'd like to try it anyhow." I had a great, big, long thesis--there was plenty of material there. Most of Goethe's ideas were wrong, but they were interesting. It was lots of fun doing that paper. Ygu must have spent not a little time in thp library. Yes, I had to do a lot of reading for that. There's one course of study that you may not have sampled, but I gather thet you did--phvsics. I took advanced physics--I don't even remember who the professor was. Well, it was Tufts--Frank L. Tufts, and his lectures were good, but the amount of work that had to be done to keep up was so great in this Advanced Physics course that I just couldn't take it. I would have had to neglect my work in chemistry, and I decided that I would abandon this physics course. I gave it up after a couple of months. It was really 54 very tough medicine. I was nev~r as much interested in physics, or in physical chemistry as I was the more plastic, organic chemistry. I don't know, byt as of this time illuminating insight of a deeper kind fro• the point of view of phyeicp and the ee••ibl• relationahipa betwe,n various eciencee--parh ■ pa relationahipe weren't explored eo much--l'm not sure. Well, a lot of people have gone into biology from physical chemis­ try, and that's a vary useful approach certainly, but I don't think that I have been a rigorous enough thinker to take that approach. Then too, mathematics, though I did well in it, always came rather hard. It was the organic side of chemistry that I liked best. I guess my son probably inherited that from me because he just naturally gravitated into organic chemistry too. It probably is the line of least resistance because it's not quite as rigorous as physics. You can't remember the fellow's name who indicated that a Bachelor of Science degree and a Ph.D. in chemistry at Columbia University was in­ sufficient for a good poet in America that would encourage you to go I think it was this man Alfred Hoffman. You provided vgurself with this extra study. and I wee wondering when YOU were in Switzerland •••• I'm aura I would not have bean asked to work in the Rockefeller In­ stitute, if I hadn't gone abroad. That was why they got interested in me. 55 You had had the conversation with them. Yes, I went down there. They knew that l had gotten a Ph.D. in or­ ganic chemistry, and that I was going to finish up with a year with Will­ statter. Better training than that you couldn't have, so at least I had the background for going ahead. They didn't know whether I was going to develop into anything decent, or not. But these were people who understood what vau could obtain from a year abroad. They all knew. I waa wondering when you were in Switzefland and had written away to all these collages and began receiving thia parade of denials--not interested-- what you thought then? I was very discouraged. I'll bet. I thought that maybe if I could get an assistantship there in Zur­ ich, I might stay another year. Bamberger actually offered me an assis­ tantship, but I didn't want to do that, if I could get a job at home. I was afraid that if 1 stayed too long abroad, they would forget about me completely in the United States. You did hurry home. ha! -r--· Yes--well, I did accept. !~actually accepted the job in Illinois. Then when this possibility at the Rockefeller Institute came up, I thought 56 that that might be even more interesting. It was to start some work in chemotherapy. It meant doing some synthetic, organic chemistry which waa a very specific job that offered very attractive possibilities. I don't went to get vou to the Rockefeller Institute--today, except the first conversation that you had with P.A. Levene, And Walter Jacobs and Van Slyke. They all figure later on. Byt this is the firet time you meet these peo­ ple. How 09en and direct were they? They were terribly nice. That was one of the many characteristics '5a,d of the people at the Rockefeller Institute. No, as I ~ ,, they were hav- ing tea in the afternoon and sitting around, and they were willing to listen to my problem and give me real sound advice. How did your Dad come by hi~ intelligence so that he could send you this news--from Meltzer, do you syppose? It was Jacobs who said that he would like to have me as his assis­ tant at the Rockefeller Institute. He knew where I lived. I suppose he wrote a letter, and it was opened. Then my father wrote me, "Come home, if you ~ant this job." Well, I liked Jacobs, Levene and Van Slyke, and I thought that they would be wonderful people to work with. The chancy things that happen--the old family doctor who becomes head of Physiology at the Institute. Oh yes, you have terrific luck sometimes. 57 Incredible. And then you go to get into a railroad compartment at random, and there are a lot cf people there from the university you think you're going to. They weren't so enthusiastic about the university, so that helped me decide to go to the Rockefeller Institute. It couldn't have been better in those terms, could it--the sprawling way in which human experience takes place. I think we'd better stop today. We've gone e little over two hours, and we'll pick up tomorrow with "Would .you like to pla:,, first violin under Toscanini? 11 which was essentiall:,, the offer to :,,au. 58 Thursday, November 21 1 1968 We left off yesterday after your veer at Zurich. I wondered looking back at that experience, that year abroad, what it was vou had picked up in the way of luggage? I understand that good jobs were not in the offing unless one did work abroad or had some work abroad. but working abroad, the elusive things that happen in a laboratory in design, or approach-­ what did you pick up? Well, I think it waan't only that you couldn't get a good job, if you didn't have European experience. It was the general realization in the United States that the quality of chemical training was not as ad­ vanced as it was in Europa and that if one wanted to prepare oneself pro­ perly and thoroughly, one had ta finish off at least over there. It waen't really until I had worked with Willstatter that I knew how to han­ dle difficult problems. The thinge that I had worked with for my doctor's dissertation were not really terribly difficult, but over there I had to work with a substance that was unstable, or presumably unatabla. One had to atart at eight in the morning and work right straight through ta three the next morning when you got the material and do all the things that needed to be done with it before it changed--it was supposed to be so unstable. It was shown later not to be really as unstable as we thought, but it was a fairly arduous year. I learned a lot of things that I would not have learned anywhere else. Who set up the controls and the techniques or the experiments that were to be done? Did Willstatter do this? 59 He planned the work--yes, very definitely, and the results were novel in some ways and expected in others. You said that he visited the labgratorv--came in tq see yoy every dav. Yes, he was there usually twice a day. Which was different from vour experience at Columbia. Well, competence, or the sense of being competent in a field. I suppose, is an elusive gualitv from beginning to end, but ea a result of this vear how did vou feel about the field of chemistrv? I felt that I was a fairly good organic chemist by that time. No problems. It wasn't that there weren't any problems. Everything is a problem, but I felt that I was better equipped to handle organic chemistry and handle the things that came up. Yesterday we had in the offing this offer from the Rockefeller Institute. We got you back home. Yea, I got a cable from my father that there was a possibility of an appointment, if Dr. Flexner wee satisfied to have me, and that if I wanted it, I should come right back and have an interview with him. I had met the people at the Rockefeller Institute and liked them, and so I thought that would be a very good place to get started. Did you see Dr. flexner? Oh, yes, he made an appointment right away, and I had a rather 60 short talk with him. Evidently I passed muster because he was willing to have me on the staff. He's wgrth a word--I said yesterday that the man who heads up an organi­ zation tends to give that organization its tone, and something of the substance of Simon flexner is worth a word. Well, he wes a very remarkable person, really, and had built up the Rockefeller Institute for Medical Research from scratch, really. He'd been Professor of Pathology at the University of Pennsylvania and had been on a number of important scientific missions. Simon Flexner was selected by the people, I guess Dr. Welch--William H. Welch at Johns Hop­ kins, who was very influential on the Board of Scientific Directors there at the Rockefeller Institute. The Board of Scientific Directors picked Dr. flexner to organize the Institute, and it was an entirely new kind of venture here in the United States to have an Institute devoted wholly to medical research. flexner surrounded himself with some of the most able and distinguished people in the medical research field here in the United States--Jacques Loeb, P.A. T. Levene, Peyton Rous, Samuel J. Meltzer--to heed the different departments. It started off that way, and later the hospital was added. Dr. flexner was still director then. Rufus Cole, who was also a Johns Hopkins man, was appointed director of the hospital. How did you feel about the medical research orientation? Or didn't that matter? Well, Dr. flexner was pretty much undisputed heed of the organiza­ tion end those were problems that didn't bother me very much. He was al­ ways very pleasant to me. 61 Direct? Yea, I didn't have so very much to do with him personally, but he and Mrs. Flexner had Institute parties occasionally at their home, and I would see them thet way. It was a relatively sma.1.l organization at the time I joined in 1912, and so everybody could know everybody else. Well, I started working--well, actually I was a little more definite­ ly associated with Dr. Flaxner than many of the other people because the chemotherapy study that was instituted at his suggestion was originally directed at finding a possible cure for polio, and that was Dr. flexner•s chief problem on which he was working at the time. Dr. Flexner always felt with Paul Ehrlich that chemotherapy was one of the great hopes of mankind for medical progress. He was very anxious to get that chemother­ apy study started. Jacobs had bean working with Levene on the nucleic acid problem for a number of years, and Dr. flexner thought that this chemotherapy study would be a good opportunity to have Jacobs start off on his own. Jacobs was put in charge of the work in chemotherapy. He had one man working with him for a year before I came, end for some reason that didn't work out very well. When this man left, I was given the position of Jacobs' assistant, and the first couple of years we worked on "the quaternary salts of hexamethylenetetramine." There was a lead there that hexame­ thylenetetramine, the compound form of ammonia and formaldehyde slightly prolonged the life of monkeys that were ill with polio, and Jacobs thought that--well, actually that was the only lead in chemotherapy. If we could modify hexamethylenetetramine so as to increase its therapeutic power, we might be able to find something that would cure polio. We made a vast 62 number of quaternary salts of hexamethylenetetramine. We coupled acetyl amines, aromatic amines and derivatives of that type, and many other types to hexamethylenetetramine and got some very highly bactericidal compounds which also seemed, in some cases, to slow down the pace of the polio viral infection. That was more a delusion than anything else because the real reason why the infections were slowing down was that the virulence of the strain of virus they were working with was falling off. That accounted for our apparently successful results. In the end we were very much disappointed and abandoned the polio work. Dr. Flexner agreed that it was not profit­ able to continue with that particular chemotherapy study, and he suggested taking up African Sleeping Sickness. Whether that wae his suggestion, or Jacobs•, or someone else•s--I don't know. We started working on the arsenic compounds. Ehrlich, or course, and his co-workers had done e great deal there, and although they hadn't produced a good cure for African Sleeping Sickness, they hed ended up with one for syphilis. The problem that we started on was the problem of African Sleeping Sickness, and the progress there was entirely Jacobs' idea. He felt that the reason that the pentavalent compounds Ehrlich had used, or that Thomas had used before Ehrlich were ineffective was that they contained mostly chemical groupings which were too reactive in the animal body, end that if you could mask these chemical groupings, you might get a very good effect with the pentavalent areenicals. The sim­ plest one which Ehrlich had used and had shown was of increased activity when you reduced it to a trivalent state was phenylglycine arsenic acid, and that was extremely toxic when you made a trivalent compound out of it. 63 Well, Jacob• had the idea that what you should do was to mask the cerboxyl group which was extremely polar and reactive, convert it into an amide group, and then it would be much mere compatible with the body fluids. Perhaps it would slip peat enzymes that would convert it, remain longer in the body, and exert a poesible therapeutic effect even though the arsenic waa still in the pentavalent state. Well, that was the sim- ~.;?.., pleat compound we mede--phenylglycin•/\ ars,nic I\ acid. It was actually the best, and every attempt to modify it resulted in something more toxic ~ a and leas antitrypanoaomal than the original phenylglycinJ A arsTnic A acid, so we wanted to call that--what was the name we wanted to use? Tryposan­ ylamide, or tryposenimide, something like that, and Dr. Flexner said, "That's a little too long. Call it trypareamide." That•a what it eventually was called. After the riret World War was over and conditions settled down in Africa, Louise Pearce who had baen Dr. Wade Hampton Brown's associate an the biological aide of the work--all the testing had bean done by Brown and Pearce, testing in animals, so Louise Pearce took the drug over to Africa. We made large 9uantitias and got a Philadelphia pharmaceutical ( 'P0....,Lr~ we•~"-il'kc,. -a,d ~cJo fc>Ykn) firmAto make fairly large quantities of the drug, and she took it over to Africa and did the field work. That work resulted ultimately in a decoration far her and for us and a Belgian prize. I objected very strongly to the distribution of the prize because, although I had no quarrel with Dr. Pearce getting the lion's ehare of the monetary award and the highest decoration becauea she did actually risk her life when she went out into the field to test the drug, it did seem wrong to me that Dr. Brown was given twice as much money as Walter Jacobs end that I got as much as Walter Jacobs did--the 64 same Belgian decoration end the same monetary awerd--whereas the entire idea for the drug was Jacobs'. It seemed to me that it was very unfair to put him below Dr. Brown who had contributed, of course, essential skills in testing the materials we fumished him in animals, but had ac­ tually contributed no ideas to the work. However, the awards had been made. The King of Belgium had signed them, and be.th the Belgian Consul General here end the Belgian Ambassador to the United States said that because the King had signed the awards, there was nothing further they could do, and nothing more was done about it. Thie particular problem was sort of a joint, e team affair--pethologist Brown and chemotherapy which suggeated the need for clinical trials too. Yes--well, that was the field trial that was carried out under Louise Pearce's direction. She trained the natives in the Congo to look for trypanosomes, and she would give them a small bar of soap for every trypanosome they found, so that they got very keen eyed about locating them. Was the Institute set up originally with the hospital in mind? The hoG­ pital is developed somewhat leter--not too much later. No, I think it was set up originally with the idea that purely laboratory work on certain, selected diseases would be done, but as things developed, it was found necessary to have patients, to study patients to get closer to the disease itself, end especially when Alfred E. Cohn was made head of the Heart Department, they found it necessary to observe human patients es well. Of course, when they started the pneumonia study, then it was absolutely essential for them to have their own 65 patients there under observation for typing, study, and treatment. Let's spend a little time with Walter Jacobs. Yea--well, ha was a very shy, quiet person and had lots of ideas. When I started work with him, I, of course, was very young and inexper­ ienced, and I learned a great deal from him. He taught me really how to carry a number of lines of work forward at the same time. If I had to reflux something over a water beth for five, or six hours, I wasn't sup­ posed just to stand there looking at it. There was always another new compound to be synthesized and started. One could always employ one's time fully. Jacobs was very able et running a number of things simultan­ eously and not getting them mixed up. He was also an extremely skillful manipulator in the laboratory, and although he broke a great deal of ap­ paratus and glassware, I never saw him break anything that had anything important in it. It was always an empty beaker, or something that didn't matter at all. Another characteristic of Walter's was that he was very hospitable. His wife Laura was too. I waa often in their home. I waan•t married yet and waa often at their home. Welter was a tremendous admirer of Beethoven. He had• pianola and all of Beethoven'• aymphonies in piano arrangement, all of the piano sonatas, of course, and everything else that Beethoven had written--anything that he could get on the pianola s ;-i,.J record. Walter Jacobs would play those piano rolls very temperamentally. A That was really a very important part of my musical edur.ation as well as my chemical education--the nine and a half years that I spent with Walter Jacobs. Was he open t9 suggestion in the laborator¥? 66 Yes, and very generous too. He said right at the beginning that I was an important part of the laboratory, end that because my being there would free him for other things, even if I didn't work on an actual phase of the overall study, my name would be on any paper connected with the overall study, that all papers would be published jointly. Walter Jacobs stuck to that throughout the whole nine years that I was there. I think I learned a lot about the treatment of subordinates from him too. I had never had anyone working under my direction before. I learned how it felt to be working under someone else's direction and un­ der an enlightened, generous direction. Walter Jacobs was extremely shy, and he didn't like to get around end talk to people. After I had been there for a month or two, I realized that I wasn't meeting anybody else at the Institute. Walter always went to lunch at the same table with the same chemists. I realized that if I didn't break away from that routine, I wouldn't be meeting anybody else there. With considerable trepidation I asked him if he would mind if I went to lunch by myself, and from that time on I began to meet the other people there and to profit enormously by contacts with people like Rous, Carrel, and especially Jacques Loeb, people who were always willing to sit and talk with us younger people even though we were unknowns. Rous especially was a brilliant convereetionaliet, and he liked to start a conversation going at a table and keep it going. Those were really re­ markable sessions sometimes. They were a great inspiration. What kind of a day was it in length with Walter JecoLs7 Oh, we started about nine and quit around five. There were no fixed hours. He got up early and came in from Mount Vernon at that time. He 67 was usually pretty hungry around twelve o'clock and went to lunch early. So did most of the other chemists. Walter always set at the same table with the same people. Ase result he wee very little known around the Institute, actually, and people would ask me about him. Most of them only knew him from hearing him talk at the occasional staff meetings he spoke at. Wea there a separate budget for his work? Yes--it was part of Dr. Flexner•s budget. What I meant was was he responsible for defending what was done in his laboratorv? Well, I don't know that he ever had to defend it; in feet, I think it was the other way around because after--well, after we had gotten trypersamide, and after Jacobs' ideas had led to an extremely active antisyphilitic which was actually tried on several hundred human cases end abandoned because--well, it wee estrange thing. We made enough for about a hundred patients, and the first hundred cases went extremely well. This drug seemed very much more active in smeller doses than selvarsan. It was really an extension cf the same idea that had led to trypars­ emide, and then we made another batch of this drug, and the patients who had been treated with the second batch, although it seemed exactly the same thing as the first batch began getting very dangerous dermatitis symptoms. The use of it just had to be abandoned because it was too dan­ gerous. We thought that if there were factors there which we were abso­ lutely unable to control, it was much better to abandon the drug. We had a long session with Dr. Flexner about it, and Dr. Flexner 68 eaid that chemotherapy of the bacterial infections had never been per­ fected--why didn't we go ahead on that, and we did. Lloyd D. Felton joined us at th ■ t time as a bacteriologist--there were several others, Harold L. Amoss and Carroll G. Bull, who came in later. ror four, or five more years we worked on making extremely highly bactericidal sub­ stances which were very effective in the test tube against pneumococci and streptococci and which in infected a~imals, usually killed the ani­ mals before the infection alone did, in spite of the highly bactericidel action of these substances. We used these substances at a relatively non­ toxic dose, but the combination of the drug and infection was usually worse than the infection alone. c:1- '----··r--· At that time we thought that ~substance had to be highly bacteri- cidal in order to be effective. We actually had sulfanilamide in our ,--------, hands, improved the method of menufacture--this :ta around 1916, 1917, 1918--improved the method of preparation, converted it from the simple, useful drug, which we didn't bother to test because we thought that noth­ ing that simple could be of any use, into highly b&ctericidal derivatives which were absolutely us2less in the treatmant of disease. If we had just done this empirically the way G. K. Domagk finally did with his dyes that were on the shelf, we would have been able to save hundreds of thou­ sands of lives in the twenty year period between our first experiments with sulfanilamide which was too simple to be any good and the time when N, it was actually shown by Trefouel, Bovet, end /:~itti to be the buaineaa I\ end of dyes that Domagk had used. Well, I used to talk about that in my lecture on chemotherapy up at P & s. I gave the last two lectures in the biochemistry course--one on chemotherapy and one on immunochemistry--and l always used to tell the 69 students that they should never allow themselves to be the slaves of an idea because our idea was that we had to make something that was highly bacteri.cidal. We.didn't conceive of any indirect mechanisms such aa were later found--enzyme blocking, or process blocking chemicals--which ac­ tually did the work very much better and were really discovered on an empirical basis and not because anybody thought of how they were going to work first. We got tired after a while of getting negative results, and we asked Dr. flexner to let· us stop. ror a long time he wouldn't let us stop. He said, "It's too hopeful, and it's too necessary." We finally got so unhappy just synthesizing new compounds of no earthly use that we both decided that we would like to have something else to do. Jacobs wanted to go ahead on the pharmacology of some heart active drugs--the digitalis group; strophanthidin, ouabain. I was asso­ ciated in working on that with him a bit. I had some ideas--some things that I would like to go ahead on. I thought that the chemistry of some of the Chinese drugs that had been used for centuries in the treatment of various conditions over there and were known to have active principles, wasn't understood et that time. I thought that Dr. Flexner might let me have a laboratory at the Institute to study some of these Chinese drugs. Well, Jacobs and I were agreed that we didn't want to go on getting negative results in chemotherapy indefinitely, end by that time he was perfectly content to have ma strike off myself too. We parted very good friends. He thought it was better for me to stand on my own feet too. I made this proposal about Chinese drugs to Dr. flexner, end he didn't like it a bit. He said, "It's going to be rather difficult to 70 find you a position somewhere else as an organic chemist,- Why don't we send you over to the hoepital"--which was functioning fully at that time-­ "end you learn some biochemistry over there, and then we can find you a job somewhere else more easily." That was in--late in 1921. I want over to the hospital. Donald D. Van Slyke was the biochemist there. He had branched off from Dr. Levene's Department when the hospi­ tal was founded end had been made the chemist of the hospital. Van said that he would give me space in his laboratory and that he was willing to teach me some biochemistry. Well, the problem that was going on there-­ the principal problem et the time was the study of hemoglobin--combining properties with oxygen and the conditions under which oxygen was liber­ ated and taken up in the body. They had had a great deal of trouble get­ ting large quantities of crystalline pure oxyhemoglobin with its oxygen carrying power intact. Van Slyke asked me if I could be of help there. Well, I looked over the situation. It was really, primarily, an organic chemical problem, and although I hadn't worked on proteins before, it was possible without much difficulty to work out a process that resulted in pure oxyhemoglobin, nice crystalline, horse oxyhemoglobin with the oxy­ gen carrying power intact. For two years I did nothing but make crystal­ line, pure oxyhemoglobin es part of Van Slyke's team. During this period Oswald T. Avery would come upstairs from his lab­ oratory, show me a little vial of dirty looking, dark grey stuff and, "See, my boy, the whole secret of bacterial specificity is in this little vial. When are you going to work on it?" I said, "I can't do it now because I'm working full time on hemo­ globin." 71 He seid, "This ie something that has to be done. We've got to get on it soon." Eventually I had time to do that. While I was on the hemoglobin work• K.,rl Landsteiner was made a mem­ ber of the Institute. Landsteiner had worked on the immunology of hemo­ globin and had also improved some of the methods of isolating the more insoluble hemoglobins. Since I had e good method far isolating horse hemoglobin, he proposed an investigation, a joint investigation, on horse hemoglobin and donkey hemoglobin. This was where I learned my first im­ munology--from Landsteiner. That was a wonderful experience--both getting acquainted with Landsteiner and watching him work and learning some of the immunological techniques from a master like Landsteiner. That was the end of the Van Slyke period. Eventually when Van Slyke didn't need any more oxyhemoglobin, then I thought I'd like to see what this stuff that Avery had was. Let me turn this over. Back in Jacobs' laboratory, how fruitful was f'elton? Well, he--actually he didn't stay very long at the Institute because he was offered a position in Washington where he had much more indepen­ dence and freedom to work on problems of hie own choosing, ao he left the Institute after a relatively short time. Hie sole connection with the chemotherapy work was testing against streptococci and pneumococci in mice because ha came with a reputation of having done some work on pnau­ mococci at Johns Hopkins. f'elton waa a good friend all hie life, although we often fought too about details. Felton had great hard luck in e way too because he wanted to do this 72 massive experiment on immunization of human beings against pneumonia with the isolated type-specific polysaccharides. At the time of the depression, when they had these Civilian Conservation Corpe Campa ha actually injected a hundred thousand young men with pneumonococcal polysaccharides. Then they had three or four other camps which were to ■ srve as controls. All these young chaps were living under such healthful conditions that there \ ~'E.~~,n.u"la\ "J! wasn't any pneumonia in theAcontral camps, not enough to amount to any- thing, eo that there never wee any proper demonstration as to whether you could protect human beings against pneumonia with these purified, capsu­ lar, antigenic determinants. It all had to be done over again later. That's hard luck. Yes, it waa really a matter of hard luck more than anything else. l:;e!.:~es, j Felton's laboratory date were all done by mouse protection end gave unin- terpretable reeulte because of the variability of animal behavior so that it all had to be done over again later. In the chem0tb1rapv work was thp problem of experimental animals a diffi­ cult one t907 No--well, it was very difficult. That was the principal difficulty, of course, in the polio work. They had to use monkeys and give intra­ cerebral inoculations of the virus, and if the virus fell off at all, then one thought one had a good chemotherapeutic result. Actually the number of animals that could be uaed was too small for any reel judgment as to whether the drug had a good effect, or not. Unless one had had a atart­ lingly good drug, one would not have known whether one had anything or 73 not. It was an almost impossible problem. The etate of the art w9a prettv tquch and go. Yes. Van Slvka himself had--I don't want a comparative study with Jacobs ba- cause Ven Slvke is sort of a unique fellow himself. Yes, he certainly is, and he was extremely kind to me. I had the run of his laboratory and really learned a lot of biochemistry_ there too. Beaidaa the research I was part of there was• great deal of clinical chemistry going on there all the time too. Van Slyke was studying the functions of kidneys and many other physiological processes, and then every once in a while important people like Dr. Frederick L. Gates, Rockafaller•s minister, who had been instrumental, really, in getting these large philanthropies of Rockefeller started--well, Dr. Gates and his wife, when they got old, came into the hospital for checkups, and I learned part of my biochemistry on their excreta and their blood. s Van Slvke--was he fruitful with idei? }I .~c-llJ,.._f(n : - -_ a~"ttcl!i _..,, Yes he wes--he got out a theory while I was there, and this was all I\ full of calculus. I had forgotten all my calculus. Van Slyke handed around copies of his theory to Baird Hastings, me, and everybody else in the laboratory. He said, "I want your criticism of this." It took me six months to recapture enough calculus to give any kind of criticism of it. Of course, my criticism wasn't worth anything any­ how. It was a beautiful theory, but before I could even understand it intelligently, it took me six months of work to recapture my calculus. 74 It was a very good exercise too. The other youngsters you mentioned--Albert Baird Heatings. Well, Ven Slyke was really a very powerful person in those days. The Hospital of the Rockefeller Institute was a remarkable place because practically everybody who went through there became either a professor cf medicine, or a professor of biochemiatry somewhere. It was almost a guarantee of a full professorship at a leading university to have had several years of experience at the Rockefeller Institute Hospital. That was partly due to the care that they used in selecting people, pertly due to Dr. Cole's handling of problems that they were investigating, and partly due to the self-generated prestige of the Rockefeller Institute. It was a place that was undoubtedly, beyond question, in tha forefront of medical research end anybody who had been associated with it automati­ cally got part of its aura. That was one of the privileges of being there. There were a lot of people who were envious end jealous of the In­ stitute because they didn't have the same opportunities fer research, and one could understand their feeling. One thing that the Institute was criticized for--and it wasn't true at all--was that there was supposed to be a tremendous pressure to publish all the time. Not once in the fif­ teen years that I was there did anybody ever try to hurry me into a publi­ cation. I'm sure that that was the case in all of the departments. They were interested in progress, interested in having things done well and thoroughly, and not interested in rushing out into print. At the staff meetings one often got pretty severe criticism, an ii t As I say, if you worked with Van Slyke--most of the people who 75 worked with him were placed. Everybody asked him, "Do you know somebody who would make a good professor of biochemistry?" That was the period when biochemistry was expanding. Ven Slyke had done a great deal to make it expand, and nearly everybody who went through the laboratory got a good professorship somewhere. I don't remember that Landsteiner was in the hospital. Landsteiner was not in the hospital. He had his own group over in the Institute itself. Another remarkable person who was there too was Florence Silbin who real.ly put the study of the tubercle bacillus on the modern basis. She and I got to be very good friends too. She was quite a person. Marvelous. ~ can't help but absorb something from thie enriched atmosphere. It was a marvelous place to be. Well, as I said, Dr. Flexner sent me over to the hospital to learn biochemistry and to go somewhere else when a good job could be found, but what with Van's work going on--I had to make hemoglobin for two years. In the course of that hemoglobin work I had the first refrigerated centrifuge made for my work. That was because my laboratory helper had a nervous breakdown. He got so many colds running in and out of the cold room uhere the centrifuge was and where we had to keep the hemoglobin all the time to keep it with its oxygen power intact that I called up the International people and said, "You have to make me a centrifuge with a cold box around it so that we don't have to expose our helpers to this 76 kind of treatment all the time." They made the first one just withe sawdust covered brine coil around an ordinary number 2 centrifuge. Everybody that came to the laboratory had to have one. The International Centrifuge Company began to get or­ ders for these things. At the Rockefeller Institute at that time we had a two months summer vacation. Relatively little work was done during the summer, and it turned out that a lot of people who had gotten these centrifuges worked through the summer. The motor was exposed underneath to the atmosphere and water began dripping down into the motors and short circuiting them. It was something that never bothered us because we didn't work in hot, moist weather. The company found that they had to take the motor out and put it on the side. Then they kept making other improvements, and now bio it's this beautiful, portable PR 2 that everybody uses:::Chemistry can't be done without it. All I ever made out of it was fifty dollars--writing a brochure for the International Centrifuge Company. But it was to halt the problem of vour helper--your assistant and the cold room. It was strange that nobody had ever thought of that before. Temperamentellv Landsteiner was a different man than Jacobs and •••• Oh yes--very different, al.though Landsteiner was an extremely shy, sensitive person too. I don't know that hie temperament was so differ­ ent. It was different in respect to his upbringing, really. Landsteiner was more or less a general in command in his laboratory--very authorita­ tive, and whenever there was an important experiment to do, he wouldn't 77 trust it to anybody else. He always did it himself, and that was, I think, the principal reason why some of his efforts at getting other peo­ ple on the staff to cooperate with him broke down eventually and sometimes very quickly because he wanted too much control of what was going on. That didn't bother me any because I was a young, unknown student really, and had never been exposed to immunology. I was fascinated when I saw him doing the crucial parts of the work, I learned from that. We got along very well together. You mentioned yeaterdav--and this wes off the tape--something about Alexis Carrel. Yea--well, Carrel was very temperamental, very French, and very ima­ ginative. At one time toward the end of my stay at the Rockefeller, I was appointed chemical adviser to hie Department and so I had rather close relations with him and with a number of the people who came from France here. He had mostly French people working with him, except for one technical assistant who really became a staff worker eventually-­ whet was his name? I'll think of it later. [Albert H. Ebeling] He hed been an assistant of the Admiral in the Navy who had been a microbiolo­ gist, and he had learned a number of scientific techniques from the Ad­ miral. He came and worked with Carr~l on the heart--the chicken heart that was kept alive for twelve years in tissue culture. They used to celebrate the birthday every year with a champagne party. There were lots of very picturesque French people who went through Carrel's Department. During the First World War there were some very fine, French surgeons. C.:rrel was very much of an apologist for French rightist movements. 78 Carrel had met Charles A. Lindbergh at a dinner, and Lindbergh wes full of ideas. He knew the subject of eerodynemics very well, and Carrel in­ .vited him to devise some apparatus for him. Lindbergh did a very remark­ able job on the apparatus, and he apparently came very much under Car­ rel's influence, under the influence of his ideas. I've always felt that it was Carrel that converted Lindbergh into the rightist that he appeared to be later on. He started out with a lot of imagination, and it'e dif­ ficult for me to see how anybody with imagination can spontaneously be a rightist, so that I think it was Carrel's influence that steered him in that direction. Certainly Carrel's book, Man the Unknown, ia really very little more than a biological apology for Fascism. It's possible that the seeds of the American first feeling was an indig­ enous thing anvwaN. It just found a leader somehow in Lindbergh. It wasn't a verv happy time. No. You--I think also, didn't vou do the chemical work for the Department of Experimental Surgery? Well, I was kind of chemical adviser to that Department for several years--the last few years I was at the Institute. I used to go over there after lunch two or three times a week end talk to Miss Lillian E. Baker who was the chemist of the Department, and I tried to plan some of the things that she was doing. I don't think that I was very effective over there. I think it was more a device to increase my salary than any­ thing else. 79 Did you come under the influence of Dr. P.A. Levene? Well, I got to be quite good friends with him. My wife and I often visited the Levenes especially after he married Anne M. Erickson. He used to entertain rather frequently. We got to be good friends. He was a very imaginative, hard worker, and he certainly laid the foundations for modern nucleic acid chemistry. I guess ho, Jacobs, and Van Slyke went about as far with nucleic acid chemistry as one could with the meth­ ods of that day which were rather primitive. He was an imaginative fellow. Yes, and he had a tremendous love of art also--a deep knowledge of it. You mentioned another man whose correspondence I have reed, some of whose correspondence I have read--Alfred E. Cohn. Yes, he was head of cardiology at the hospital, very much of a schol­ ar and had people like Harold J. Stewart, very good people working with him. I don't know how much real progress in cardiology was made es a re­ sult of his being there, but there was always sound research being carried on in his group. Ypu didn't have anv direct contact with him? No. This Harold Stewart--waa this Harold "Red" Stew■rt 1 a pathologist? No. I don't think so. He was Professor of Medicine at Cornell for BO a while. I don't know whether he's still at Cornell or not. He kept on in cardiology. Hideyo Noguchi wes another picturesque character there at the Insti­ tute. He used to come in very late at lunch, usually in his lab coat and f ,j "1 ,11 ½--_______, with a tube of spirochetes in his coat pocket. It didn't seem to matter, I\ to have lunch with the laboratory vestiges all over; k.,.r c ,,at• Was he outgoing? Yes, he was relatively talkative. I used to meet him occasionally on the bus, or en the street ear. There was a street car, the 86th Street vt_f'S6 car at that time going through the transf.R;e. When they made him a mem- " ber of the Rockefeller Institute, he said that he felt that they made him a member too soon. I don't know whether he really meant that, or not. "Fess" Averv--Professor Oswald T. Avery is quite a person. Yes. As I said, I was supposed to leave the hospital end get a job somewhere else, but these things kept coming up all the time. I was needed by Van Slyke, and then there was this problem of Avery's. As soon as we started working on that problem, it began to look as though Avery really had been rightJ that one of the chief problems of bacterial specificity was involved. It was several more years before I could leave, but Dr. Flexner insisted that I should leave. I worked with Avery, I guess it wee for about four years, and was extremely happy doing it. I learned enormously from him. He was a man of wonderful intuition. He was ex­ tremely kindly and eensitive, and I was perfectly satisfied with the con­ ditions under which I was working because whenever there was a chemical 81 paper, he said, "Your name has to go first on it." It seemed to me that that was all the recognition I needed. Dr. Flexner said, "As long as you're here and as long as you work with some­ body else, it's going to be known as someone else's work, and if you want to be known yourself, you'll have to go somewhere else and stand on your own feet." I didn't like that idea because I was perfectly happy. Dr. Flexner insisted on it. I found later that he was probably right, that one has to have a position of independence if one does want to get known, but I don't know that it really would have made so very much difference. This was exciting work with Avervl It was--it was tremendous. I was actually in the hospital for sev­ en years, although I was supposed to be there for only a year or two while I was learning biochemistry. Dr. Flexner didn't want to interrupt the polysaccharide work during its development. A. Raymond Dochez and Avery had found the soluble specific substance and realized that that was the capsular material of the virulent pneumococcus and that each type was immunologically specific. They wanted to know what the chemical basis of this substance was. Everybody thought at that time that it had to be some kind of pro­ tein. There were three possibilities to start work on. At that time the pneum0c0cci were classified into the three "fixed types" as Avery called them--Type I, II, and III. Everything that wasn't one or the other was thrown into group IV. Avery said that the best type to start with would be Type III because "it has the biggest capsule, but some people say that it isn't• pneumococcus. They call it Streptococcus 82 fY\.l.tC<..,s; .. S mwo2ea:i:s and so we can't start with that. If you want to be logical, you can start with Type I because that's I." That was F. Neufeld's original pneumococcus. Actually that was the one that Hans Zinaser and J. H. Mueller started work on, and that led them astray, Avery said, "Let's take Type II becmuse that gives you an intermediate amount of material, and it's easier to work with if you get w1flt '-r.:--' more stuff than~Type I." -t ke.. We started with Type II, and the more I purified it, ~ lees nitro- " gen it had in it. Avery came up one day and said, "Well, if it hasn't got any nitrogen in it, what can it be--a polyaeccharide?" That's what it was. Then we worked on Type III, and the minute I got the first partially purified preparation, I knew it was different from the Type II because the whole feel of the thing was totally different. Then when I want back to work on Type I, I threw most of it down the sink because I thought it was a polypeptide impurity. We didn't heve quantitetive immunochemical methods then. Those were developed later. Just making dilution tests ,£'\ with material with the properties cf a nucle-. protein didn't seem very I\..._,., important. It went down the sink, but then moat of the type specific material disappeared with the material that went down the sink. It turned out that the Type I was really the mast difficult one ta work with, and we still don't have too clear an idea of its composition and fine structure. That wae where Avery's intuition led us to a useful result. Zinsser and Mueller who just started on the most logical one, because it was Type I, went wrong and thought that it was a polypeptide. It was very easy to think that it was a polypeptide, although we know now that most of it is galacturonic acid, but it had all of the properties of a 83 j_~ polypeptide, as an amphoteric polyelectrolO:Mo-. /\ This particular study is relevant to a much bigger stream--the Pneumonia Commission in the First World War, isn't it? Yes. We've overlooked how that war affected you and the Institute. Well, we were all working on war problems. During the First World Wer I was put into the S nitary Corps, but we were working on the anti­ syphilitic at that time. It wasn't until after the war was over that I went over to the hospital. But both Avery and Dochez had been on the Pneumonia Commission with Fran- cis Blake, Tom Rivers, and others. Yes. Well, Francis G. Blake was still at the hospital when I first went over there and Charles Philip Miller. They were all people whom I had met at lunch, but didn't know very well in any other way until I actually went to work at the hospital and took part in the hospital staff rounds that they had every week. There one saw really what a remarkable person Dr. Rufus Cele was. He would sit ther6 and listen to whatever was going on, and then he'd ask a question. Sometimes the question seemed almost naive for a person who was supposed to know as much as he did, but the result of this question always wao to bring out things that hadn't been brought out before and to get much deeper down into the pro­ blem than one had before. Dr. Cole was really quite remarkable that way. It was really a pr.ivilege to be on the pneumonia team, and all through that time I kept working end using a vast amount of space in Van 84 Slyke's laboratory, and he never once objected to that. He was really very generous, very helpful. Thev had visited aeverel cppp in the United State• and hed collected material. Thex had lotp of material to work with. Someone told me-­ let•e •••• Tom Rivers stopped off in Johna Hopkins and worked in Dr. Bayne-Jones' laboratory for' briet period. and he h@d all kinda of mg­ teriel to work with of. viral nature from tbia·commiaaion. Yes, Rivers was the first real virologist that they had had, or the first person who was enough intereated--I don't know whether his train­ ing even fitted him to be a virologist, but he certainly became one of the country's leading virologists. He was forced, I guess, by circum­ stances to take an interest in viruses and became one of the most able virologists we had. Part of the problem ia dg YDU have material--they had material. plenty. Yes. We had problems of getting material, of getting enough poly­ seccharide at that time too. I used to work up three hundred liter batches of broth and concentrate them on the water beth, precipitate with alcohol, separate the junk from the non-junk--it was e tough job. It wasn't until later that greatly improved media came in, and then one could grow pneumococci very much better than one could at that time. You would get a alight haze in your flask and that was that. You had to work with what you had there. Then the pneumococci autolyzed so read­ ily that in the ordinary v~al infusion, or meat infusion broth that was used, you had to use the whole broth and you had all of the meat infu­ sion as part of your impurities too, so that it was quite a problem to 85 separate the material. We never really had it absolutely pure, I think, except the Type III--meybe. You mentioned enother fellow vegterdav and this also was off the tape-- Dochez. Dochez and Averv worked pretty well together--complemented one another. Oh, yes, they were a wonderful pair. for many years they shared an apartment together along with one or two other people usually at the Rockefeller Institute, and each influenced the other enormously. Dochez was much more the contemplative, imaginative type. Avery believed in experimentation--careful, meticulous experimentation, repeated and re­ peated until you were absolutely sure of the result. Each complemented the other, and they were a marvelous team. You mentioned yesterd9v that it takes not a little luck--the right dash of intuition and lots of experience. I certainly had the luck. But to discover the sugar links in the capsule. Well, we never got very far in working out the fine structures be­ cause the methods of sugar chemistry were not very well developed at that time either, but we found out some of the sugars that were there. We missed one of them in Type II. We got the structure, I think, of Type III pretty nearly correct, except for the actual position of the 11 .....,,_, linkage between the two sugars. That was when Walter F'. Goebel joined A the work. He had been a student of Willstatter's, I interviewed him in Paris. They said I could have an associate chemist, and I interviewed B6 Goebel in Perie, and took him on. He came the following fall and worked with me. It was the first time that I had ever had anyone working under my direction. You picked a good man. Yes, he was very good. What--let's see, you'd been with the Rockefeller Institutu since 1912. Did it act as a beacon to the laboratories in the rest of the country? Yes, I think so. I get this from the correspondence, that people begin to check work done at the Institute, try to get the same result to a problem. and the cor­ respondence develops where one differs, where the methods aren't quite clear, or have not been quite clear, and the effort seems bent in making them clearer. Did you have this sense that tho Rockefeller Inatitute wee really leading? Yes, we always felt that it was out in front. There were lots of other people who denied that it was, but I think it was mostly a matter of envy and jealousy because where else in the country could you have all of the facilities that you needed and full time to do research? When I went tc Columbia later I learned that it was very good to have some teaching responsibilities. Perhaps the Institute, now as the Rocke­ feller University, is even better off having teaching going on there, but et that time at least it seemed e perfect life to be devoting one­ self to research end actually finding out new things. 87 I guepa from 1921 on, the handwriting was on the wall that vou were go­ ing to h1ve to look fore poat elsewhere. although these othe; matters •••• Yes, Dr. flexner never changed his mind about it. There were people who gossipped about it, and said that it was other people who were sort of jealous end pushed me out, but I never believed that. Yau never had that feeling? No. And moreover from the etert he was direct with you--Dr. flexner. Yes, he told me that--when was it--in 1921, I guess, that I should get out and stand on my own feet, end he never changed his mind. You got backed into things that were going on. Ye1. But I wonderpd in the period from 1921 on whether YOU had an idea es to where you might conceivably 6ight 1 if poatible. No, I wasn't interested in looking around even. I was so much in­ terested in what was going on I had no reason to look around. There were two very nice things that the Inatitute did--one on the material side, and the other wee aort of spiritual, I guess. On the ma­ terial side, after I had been there for ten years, they started a pen­ sion plan--Teachers Insurance and Annuity Association. That had been started at various universities, and the Institute decided that they would come in on it. Well, the members of the Institute were given a 88 choice. They could either come in under the Teachers Annuity Plan, or else the Institute would take care of them in a private pension plan of their own, but those of us who were below the grade of member had to say whether we wanted to join the Teachers Annuity scheme, or else be left out of everything. Well, there wasn't any alternative really. We could afford to have a modest deduction of 5~ taken from our salaries which were rather low too et that time. The only alternative really was to accept that because otherwise we had nothing. I said that I would come in under the plan, and the thing that developed was that they gave me a fully paid up poli­ cy covering the first ten years that I had been there to which they con­ tributed the 5% that l would have had to contribute over those ten years. That, of course, gave me a wonderful boost toward a pension. I thought that waa an extremely generous thing to do. It gave us younger people who ware on small salaries a very good feeling to know that they at least took that much interest in our future welfare. Then--let's see, oh, the other thing was that they didn't have any sabbatical system. After this work with Avery had prospered and had gotten to a point where it could be at least interrupted, Dr. Flexner sent me off to Europe on a sabbatical. He said that he thought that it would be good for my development if I would look around the leading lab­ oratories in Europe. That was the first time that anybody had ever been sent off on a sabbatical from the Institute, and I fixed it so that two of the five months that I was away were the summer months, and the pneu­ mococcal work was interrupted for as little time as possible, but it was really a very wonderful trip that I had. 89 Was that 1927. or earlier? This was in 1924--April of 1924 I went over, I remember. I went to see O. Warburg, and I went to see Willstatter again. I saw M. ~ ~~--..-·-~· and A lots of the leading organic chemists and biochemists--C. Neuberg. Warburg himself •••• Well, Warburg I didn't like. I went to see him, and he showed me around a little while. If they knew that you were from the Rockefeller Institute, they felt that they had to give you a little time anyhow, even if they didn't know you personally, and he said to me, "What are you doing?" I said, "I'm very much interested in immunology from the chemical standpoint." He said, "From the chemical standpoint? What right do you have to have a standpoint? You have to look at everything from every standpoint!" Well, I suppose he was right, but he just jumped right down my throat on that. I said, "I can't help it. I'm a chemist. I'm trying to learn biology." That was a terrible way •••• .~ Well, he was always a very positive, abrupt sort of• person. Another most remarkable thing about the Institute was that every­ body in the whole world, who was doing significant medical research, sooner or later came to the Institute, and you always met them and had a chance to talk with them, end that was a rare privilege. It was funny. They had a business representative et one time, a 90 ~ man named Gfpper who took charge of the business administration. All of the nonscientific visitors who were attracted to the place because of its fame were steered into his hands. Dr. Flexner took care of the sci­ entific ones and brought them a~ound himself, especially the more imper- tant ones, but the relatively nonscientific, or less important ones, were ,R,J always brought ~round by Gepper, and he would throw open the door of the A laboratory and say, "Just another chemical laboratory!" Then he'd slam the door shut and take the visitor along. That was wonderful. You said that you saw your old teacher in Zurich again. No, he was in Berlin by that time. That's right. The corresgondence shows Germany. When was it that I saw him in Munich? I guess it must have been-­ was he in Berlin? Or was he in Munich? I think Munich. It was Neuberg that I saw in Berlin. I'm not very clear about that. It seems to me that I saw Willstatter in Berlin too in 1924. It wee on a later visit that I saw Willst~tter in Munich. I think Willstatter was a bit surprised that things had turned out es well for me as they did. Certainly when I went to him, I had had relatively little experience in handling problems of the sort that he was interested in. Pleasantly eyrprised. I hope. 91 Yes, I'm sure that when Avery got the gold Ehrlich Medal and I was given the silver medal, it was Willstatter who was responsible for that. Willstatter visited America during the year I was at Mount Sinai Hos­ pital, and of course I saw him then. In going around these laboratories, did you find new equipment that you didn't have? Yes, there was a whole Institute of Organic Chemistry in Leyden that I was very much interested in. I think it was probably the first separ­ ate institute building of organic chemistry in the world. That was a ,;; very impressive place. Then I saw P. Karrh in Zurich where Willstatter l\ E, .-,.., had been before, though Karr;r was at the University and not at the Polytechnic. Did this give you a comparative view of work being done. or people doing it? The nature of laboratories? Well, I went mostly to people who had been names that I had known before and were known for their research work. Very often they were work­ ing under conditions which seemed relatively primitive, and there wasn't so much new equipment that one could see. It was mostly the privilege uf talking with people whose names I had known all my scientific life that gave me the most on a trip like that, You certainly get e sense of the international neture of science anvwav. Oh, yes. It transcends state linas--Et least I believe §O, 92 Well, I've always been very strongly attracted to that aspect of things. My first wife was very much interested in the League of Women Voters and the American Association for the United Nations. She was on the Speaker's Bureau of both of those organizations. Sha had a study group on foreign policy in our district at hom6 and conducted that for many years. After she died, her friends asked me to try to carry on her work as much as I could, and although I knew nothing of it except what I had absorbed from her, I was et least going to Europe to scientific con­ gresses and things like that. The American Association for the United Nations didn't have money to send experts over so they would get a dele­ gation--Clark M. Eichelberger, the executive secretary, and a few inter­ ested people together, people who could afford to pay their own way. I was going anyhow so I was put on the delegation. My wife died in 1946, and in 1947, there was a meeting of the World rederation of the United N~tions Associations. I was going over to meet­ ings anyhow. This World Federation meeting was held in Prague. I went with the American delegation and found that because I knew French and German, I could really be of some use, even though I didn't know very much about what was going on otherwise. Actually I was able to resolve differences between the English and French versions of two resolutions which the World Federation were interested in and which actually came up that following winter in the General Assembly. It was a tremendous thrill to me to have had something to do with those resolutions. I felt that the individual actually could take part and do something to foster inter­ national good will and feeling. I went to five of those meetings including the first one in Asia, in Bangkok. I gave lectures in Japan for a month tn pay for that trip, 93 and that was a wonderful experience too. As a result I made lots of friends in that field too, especially among the Norwegian and French delegations, and some of them were lasting friendships. We'fe just about at the end here. Let me put on another tape. I want to start by going beck and pick up people with whom vou worked and about whom you might comment, and one is Amoee. Harold Amoss? Well, I never got to know him particularly well. He was very compe­ tent, very able, and I think he was only there at the Institute for three or four years et most. Did the Institute have e policy whereby it brought people in end thrqugh as e method of training? Yes, they couldn't establish a new department for everybody. The general idea was that you were to be there for a few years, and then you were to move on. I only note that in Jacobs' Department Amoss was one. How about Bull? Well, Carroll G. Bull was only there for a few years too. He went on to get a professorship, I think, down South somewhere. He was a southerner. Harold Amoss was too. There waa a woman there too--Ida Relf. Yes, Ida Rolf was e chemist, an organic chemist, end ehe worked 94 there with us a couple of years--got mar:ied, I think, but I'm not sure. I just note that she wap there in Jacgbs' laboratory. The ng,nep of these three people figure in some papers that were written, Now in Jacobs' laboratory. haw were papera written? Did YOU have a hand also in the writing of papers? Yes. The things that I actually did myself, I usually wrote up. Then we combined them end arranged them in whatever order we thought ad­ visable. We had a lot of trouble getting our cinchona alkaloids work published. Yes, because the American Chemical Society said that there wasn't any interest in alkaloids in tho United States. They would have been happy if we had sent the papers to a European journal. We didn't want to do that. They published them finally. Waa the same thing true in Ven Slvke'g labgratorv? for example, I men­ tioned the neme this s>rning of Baird Ha•tinge who wa■ there brieflv. He was there mere than briefly. He played a very important part in the hemoglobin work, and then he went as professor--where did he go to? Michigan I think first, though I'm not sure. I'm net either. Eventually he was at Harvard. He had a long and distinguished career. But as of this time do ¥DU remember anvthing in particular abqut him? He was just a young Ph.D., very competent, very able. We worked 95 together in the same laboratory several years. James M. Neill was another one--Jimmy Neill. They were all very active, hard workers. Par fpr the course at the Institute, I suspect. One expected that, I guess. There is a man who isn't listed--Cherles R. Hartington. '-· Oh yes, Heijington. Hewes an Englishman. He came over for a year also on a Rockefeller Fellowship, I guess, but I'm not sure, and he was in the same laboratory that I was. I got to know him fairly well. We always visited the Ha#ingtons everytime we went to England. He became director of the National Institute for Medical Research. He was really a protege of Hanry B. Dakin, I think--probebly a student and co-worker of Dakin on insulin. A biochemist? Yea, he is e biochemist. Then there was a fellow named Henry A. Murray. Yes, we were good friends too. He was a very bright chap. He got more interested in psychiatry, I think, afterwards, but he did some bio­ chemical work. Edgar Stillman was in Van's group. He was a clinician and interested in the kidney work. Ha died this last year. He was a very agreeable person. These were some of the people with whom vou had ready contact. Yes, then Palmer--W. W. Palmer. He had known Vun Slyke, I think, a 96 long time, and in between a professorship at Johns Hopkin• and I think hia new position at Columbia, he came for a year to work with Van Slyke. That•a how I got to know him. That's how I was offered the job of chem­ ist to the Department of Medicine at P & s. I didn't know that. Oh yes, it was because Bill Palmer had been in Van Slyke'a labora­ tory that we came together. That'• great. Th1re are e few others that vou may not have been asagci- ated with. Well, Dochez, Hugh J. Morgan--all those people--I knew them all when they were there. One is Homer r. Swift. ~~ Yea, Homer Swift, Rebecca lancefield--they were all there and Edliia A Todd who worked with Lancefield for a while. Alvin r. Coburn was even there very briefly before he went up to Columbia. Theobald Smith. Yea, I knew him too. This wee en exciting place. Yes, it was. Well, Theobald Smith one used to eee around before the Institute was established down at Princeton, and then he became dir­ ector et Princeton and only came in to New York City for important occa­ sions after that. 97 Did you get in this period--much chance or much need for library work? I reed the journals, of course--had to read a lot of journals. I did some abstracting at that time for Chemical Abstract• too, but I only read the papars--abstracted the papers that I was most interested in, sent the cards for the abstracts out west to Louis Wise and let him do all of them that I wasn't interested in. It was. hard job even then, I suspect. keeping up with the articles. It was a lot of work, but I hadn't branched out so much in those days. That was before I became an immunochemist. It wasn't really until I started working with Landsteiner and with Avery that I abandoned more or less straight organic and simple biochemistry--if it's simple. Thie morning we ended on the fact that you had a sabbatical in Europe. Yes. An opportunity to meet with and talk with other ehamiata, organic chemiata, see their laboratories, examine the st■ te of the art in Europe. Was the thought then that this sabbetical would bathe apringbaard for you to go elsewhere. or no? Nothing was ever said about that, and it was three years before I left the Institute actually, so that I don't know whether Dr. flexner had that in mind or not. In anv eyent, he thought that this sabbatical would be a good thing for ~- 98 Yes, eo he sent me off. Just how many other people were given the same privilege I don't know. Qne of the things the Rockefeller Foundation was doing was bringing peo- e,• from abE9ad over here. Yes. It seemed that this w91 a reverse proceaa. [The phone rings] It mav have been. Well, I don't know how conscious that waa. The Rockefeller Founda­ tion had its viral study laboratories up around the Rockefeller Insti­ tute at that time too. Evidently that phone call was not for me. Evan tha;f interest in tropical medicine. Well, the malaria work was originally carried on down at Princeton. There wasn't too much contact with the Princeton people. John H. Northrop Wa0~M~S had worked with Jacques Loeb and with an Auatral.ian named ~ a who had worked with Loeb. Well, de Kruif was there at the time too--rather briefly, and he worked with Northrop and Northrop was very unhappy with city life, and he persuaded the Institute authorities to let him go dawn to Princeton. He•• e first rate fellow too. Yes. There was s certain furor about the plant--de Kruif'a publications, his popularization of their science. I don't know whether you were in it, 99 or disturbed about it, or otherwise affected by it. I knew de Kruif fairly well. He was passionately devoted to music so that whenever we had a musical party, we'd invite de Kruif. He had rather a good deal of difficulty deciding whether he should be a writer, or an experimental scientist, and it was decided for him by Dr. Flexner. Yea. He was pretty indiscrete, I think, and deserved what he got. In a sense, an effort to convey to a wider audience some of the excite- .!!!!!!.1• ••• That wasn't why he left the Institute, or was asked to leave the Institute. That was for other reasons, but I think everybody there ap­ plauded his popularizations of science. They didn't always agree with the way he had interpreted people's personalities. I think his books served a real service. When you returned. vou still worked with Avery. Yes, I went back to work with Avery, and ea I say, I fixed it so the interruption wee as brief as possible. We were really getting re­ sults, and I didn't want to interrupt it too long. Thea ■ p ■pera with Averv--euthorahip. How do ,vou handle a team approach, or te,m thinking in a publicetign? Well, on the things that were primarily biological his name appeared first, and the papers that were primarily chemical had my name first on 100 them. That was e perfectly satisfactory arrangement. Coulgn•t be better. He had regard fgr your chemical insight. and vou had regard for his bio­ logical intuition and insight. Yea, of course. You did indicate that there was a great deal to his intuitive guesses­ his feel. 1 guess. Yes. Well, he was sure that this capsular material was the key to the nature of biological specificity. At this point it would be good, I think, to say something about Rebecca c. Lancefield because ahe wee working with Homer Swift at the time. In general, people there at the Institute didn•t consider her very much more than a kind of exalted technician, though I think she had her Ph.D. then too. When we came out with the polyaaccharide nature of the type specific substances of pneumococcua, we thought, of course, that atreptococci, a closely related group, ware going to be very much the same. The then current scientific fashion was to consider that they were going to turn out more or less the same. Well, the actual work was being done by Rebecca C. Lancefield on the streptococci, end she found that there wee a group specific carbohydrate just as with pneumococci, but when it came to the type specific substances, she couldn't find any carbohydrates. They were proteins, end in spite of all the trend of feeling of the times she stuck to her guns. The scientific evidence was 101 there, and she maintained that the type specific substances were proteins and not like the pneumococci, and she was right. Well, it took a good deal of strength of character, I think, and originality not to get lost at that time in the feeling around the hos­ pital, the enthusiasm there was for this new idea--polysaccharides--"that•s the whole secret of bacterial specificity." Well, ehe put her finger right on it and said, "It isn't." It was important, but it wasn't the secret of the whole thing. I've always respected her very much for that. She wasn't going to be intimi­ dated. Intimidation--there wasn't any effoft in this respect. No actual intimidation. It was just the fashion of the time--a lot of people went along, but when her work indicated that ehe shouldn't go along, she didn't. Good for her. As--let's see, in the l920's--in 1927 what appeared on the horizon--you know, ultimately a jump where you could begin to get out from under the shadow of othe51, as Dr. flexner advised? Well, the thing that happened first waa that the chemist at Mt. Sinai Hospital retired, or announced that he was going to retire, and they looked around for somebody to take charge of the chemistry at the hospital. I had known Dr. s. S. Goldwater. I don't know whether it was he who suggested my name, or perhaps it was Levene who suggested my name to him--I have no idea. Anyhow, I was asked to come up there and talk 102 to the people. Louis Gross was the Director of the Research Laboratory at the time. Gregory Shwartzman had just gone there--rather he had been there a year or two working. There were a number of people whom I knew on the medical staff, but I didn't know very many people who were doing scientific work there. I thought the matter of my leaving over. As long as Dr. Flexner insisted on my leaving and after we had shown that the polysaccharides of the three "fixed types", so-celled, of pneumococcus I, II, and III were different, I thought that if I had to go, that would be a good place to break it off because the fundamental part of the job had been done. The three different types were shown to have different chemical constitution and so somebody else could go on with the details. Mt. Sinai Hospital made me a reasonable offer, promised to give me opportunities for research, give me a co-worker, a full time, research co-worker, and so I took the job. Well, I found that the clinical meth­ ods that were being used in the laboratory were about the ones that pre­ vious chemists had brought with them forty years before and that very little actual progress had been made. Everything was being done in a terribly old-fashioned way. There were a number of rather unpleasant thingo that happened at first. There were some people around that I didn't like. I looked over the staff there, the technical help, and I was advised to get rid of two people--an old German who was the laboratory diener, or helper, and a Chinese who was around in e sort of nondescript position, e partially trained chemist who had just been in the laboratory. After looking into it very carefully and accepting the job I threw everybody else out and kept the two people that I had been asked to throw out. I didn't trust the judgment of the people who told me to throw those two out, and I 103 found that I was right. I had the Chinese as my own personal technician for thirty-five years after that. He went to Columbia and to Rutgers with me. He was a marve­ lous person. The old Germen diener was a very faithful, hard worker who kept the laboratory in good shape. Also he told me of some of the prac­ tices that were going on after the doors were locked in the evening. Some of the younger people on the hospital staff came in and did their own pri­ vate laboratory work with the hospital's carefully calibrated reagents, apparatus, end equipment. Practically the first thing I did was to have all the locks changed, and after that things began to move rather smoothly. I had a very good man--I think he was from Chicago, a man named David J. Cohn who was appointed assistant chemist of the hospital, and he took some of the burden of the routine off my hands. Practically every method in use for clinical testing had to be changed, and that was quite a severe job. I found that research was going ahead very, very slowly, In the meantime Dochez and Palmer had gone up to Columbia from Johns Hopkins, end they were down at the old Presbyterian. They were building the new medical center up at Washington Heights and were going to move into it in 1928. Bill Palmer appeared one day and said that he would like to have a chemist in his department, a full time, research chemist, to do whatever he wanted--just to be there for consultation and advice whenever chemical advice was needed in his department. Ha went out and got a half a million dollars from Edward Harkness. That was the Harknaaa Research fund of the Presbyterian Hospital and my salary, and salary of a co-worker, and the expenses of research that I did absorbed all the income of that fund from the very beginning and for the whole twenty- 104 seven years that I was there. When it finally came to the point of my beirtg retired, I felt that they were quite justified in changing the emphasis of the chemical re­ search in the department. It had been along one line for twenty-seven end a half years. There was a new professor of medicine. He had his own ideas and was certainly entitled to a change. I could be very philosophical about this because for several years before that Dr. Selman A. W,,ksman had been asking me to come down and ~ ~ , " ' ' Lo,,,,~r,~ start an immunochemical unit at his Institute of Microbiology. I had A been going down end giving seminars before I went down on full time. The year before I was to be retired from Columbia I went down there on full time--Columbia wa~ extremely generous, gave me a year's te:cminal leave with full pay, actually, and gave me all the personal equipment-­ all except the heavy things that other people could uee; the centri­ fuges and things which Rutgers supplied anyhow. Since there was to be a change of emphasis in the department's chemical research I took my whole staff along with me, Otto Plescia and my technicians. We took a whole truck load of our own special equipment along which Columbia generously let us have, and within two weeks of the time we got down there we were functioning just as though we had been there for years. Moving meant no interruption whatsoever, and this move was a year before my official time of retirement. Then I became emeritus professor at Columbia. I had al­ ready been appointed visiting professor at Rutgers, so I went on down to Rutgers for another nine years. I'm very much interested in this Mt. Sinai Hospital. It's true that Dr. -, Samuel Brookman had announced his retirement and a man who had headed '- 105 pathology died that year, Dr. Fred S. Mandelbaum, so that a,void was ere- ated which allowed some alteration and change. Yes. I never knew him. I had met him, but I never knew him very well. I think Dr. Isidore Friesner was head of the Medical Board at the time, and he backed me up. Goldwater backed me up too. For instance, there were a lot of small questions that came up. The purchasing agent, or the vice director who had something to do with the purchasing agent, was always very sticky about alternatives, if you could get something cheaper. Sometimes I didn't want the alternative, and whenever there was any major question of that sort, Goldwater always backed me up. The only other real conflict I had up there was with the Medical Board. The one summer th~t I spent there was extremely hot, and condi­ tions were not too favorable for doing laboratory work. The hospital had a habit of asking for nonprotein nitrogens and also blood ureas on every case, and I refused to do both during the summer, especially the nonprotein nitrogens. J They requirera micro Kjeldahl, and it was too hot ~ to do them. "If you can show me that it's a research case, that you need those data, and that you can't get them from the blood urea, then I'll do it, but for en ordinary routine case I refuse to do it. I won't put my personnel through the summer trauma of having to do Kjeldahls in the heat." Several members of the clinical staff were so angry et that that they had me up on charges before the Medical Board. That was the only disagreeable incident. The Medical Board didn't take any action. Goldwater took my part too. He was the superintendent. He said that I was perfectly right. 106 I was glad to get out of Mt. Sinai Hospital really, partly because there was a vast amount of routine and quite properly--you can't run a hospital without doing a lot of chemical routine. Somebody had to super­ vise this routine, and although my associate Cohn was capable, there were a lot of things that I had to keep my eye on. Then too by that time I was convinced that it was necessary for progress in immunology to have some better methods than just titration& and dilution end points which didn't tell you anything, and that the main problems of immunology would never be solved unless you could apply analytical microchemistry and get some real data in absolute units. Cohn and I started that work at Mt. Sinai, but we never had much time to devote to it and really get it go­ ing to get any real results. No progress was made until I got up to Columbia. You went to Mt. Sinei 1 end you had this idea then on going. Yes. Is this a consequence of work with Landsteiner? Well, Landsteiner and Avery--well, a consequence in part of reading Bordet's Traite de l'lmmunite (Masson et Cie, Paris, 1920) which was a magnificent book, even though a lot of it was completely wrong. It just read like e novel, and it fascinated ma with the subject of immunology. There were so many things that you could do and so many things that still needed to be dona, and there were so many unsettled questions between Bordat and Ehrlich that it seamed to me that I could do something with those questions. I had talks with some of the people at the Rockefeller Institute about it. I talked it over with Avery. He was all far it. 107 Landstainar--I don't know whether I ever told him any of my plans. Jacques Loeb influenced me a great deal by his work, but he wanted me to stick to hemoglobin. He thought that there wasn't anything in immunology, that 1 would do better to stick to hemoglobin. I was very much interested in hamoglobin. It was a little discour­ aging after a whila. I had the idea that because the iron atom w■ a in there, it should be possible to get x-ray pictures of the molecule. Thia I was back in 1920, and the only people who were doing x-rafrystallography in this country--if I had gone to W. J. Bragg's laboratory, something might have come out of it, but the only people who were doing it in this country were up in the General Electric L;;boratory. There was a Wheeler P. Davey in charge. The General Electric people were interested mostly in the properties of metals. They were equipped for metal crystallo­ graphy, but wave lengths were too short, I guess, for protein chemistry. I went up to Schenectady with a thermos bottle filled with beautiful hemoglobin crystals and came back with nothing but a reflection of the slit from the spectroacope that we used. 1 That was very discouraging. I think I probably made the first x-ray photographs of hemoglobin. That's the hope of chemiata today--to take metallic derivatives of the ~it proteins and to orient the amino acids around them. •~-ray A photograph ■ of hemoglobin didn't work out. That rather helped, I guess, to confirm my interest in immunology and to strengthen the feeling that maybe with my organic chemical and analytical background I could do something to make things better in immunology. Mt. Sinai Hospital was not nece1sarily a research oriented place. 108 Yee--they had a department, or a research laboratory in pathology. They had just built a new laboratory building, and each head of the de­ partment--microbiology, bacteriology as it was called then with Shwartz­ man; chemistry; and pathology--there were three main divisions, and each division was supposed to do research; in fact, we had vast laboratory space. There was no question about space. They gave me all the money I needed for research. I just didn't have time to do very much. One had to do the routine when there were patients there who were waiting, and I made it known that if any of the staff had research projects, I'd be very glad to help with them. Any number of them came and outlined very inter­ esting clinical biochemical problems that they had thought about and thought very effectively about. They said, "Well, will you do this?" I said, "I can't do it, but if you'll take one of your younger men and send him down to the laboratory and give him time, I'll give him supervision and see that he works along sound biochemical principles." Well, practically nobody was willing to do that. They all wanted me to do the ~esearch, to work on their ideas. I told them that I had a full time job running the chemical laboratory and trying to start some research of my own and that although I thought their ideas were excellent, they would have to send somebody to work on them. That didn't work out. When I was offered the position of chemist at the Presbyterian-- my title was Chemist to the Presbyterian Hospital and Chemist to the De­ partment of Medicine--and I was given an Associste Professorship of Medi­ cine right away, that was vary attractive. I thought that I wouldn't mind doing a bit of teaching if there was teaching to do. That's how I went to Columbia. I was only at Mt. Sinai for a little over a year. Another of Willstatter's people who had come over to this country, Harry 109 Sobotka, was my successor over there, and ha held the job until his death. There was one man who worked in the laboretorv--Nathan Rosenthal. Yes, 1 knew him--a hematologist. He was a very fine, quiet person. I never did find the man •••• And Reuben Ottenberg was another one who--tha first one really to introduce Landsteiner's blood group work hare in this country, the first one to do really blood matching. I think it wae when Ottenberg retired that Nathan Rosenthal took over. Then there was• Joseqh Friedman in the Chemietrv Deqartment. Joseph Friedman? Joaaqh 5. Friedman•• •••iatant chemist. Friedman? I'll have to get my glasses. The men I had was named Cohn-- p. J. Cohn. This PIP!£ l¼ste Nathan Ro1anthal. Cohn end Josephs. rried­ man--this is the study on the "Behavior of the substance active in earni­ cioua anemia •••• " Did I actually publish the little bit that I had done on that? I guess you did. [78 Jo4rn9l of Biglogical Chemietrv lxvi (1928)] I have no recollection whatsoever of Friedman. He must have been one of Roaenthal'a people, though it does say assistant chemist. Why 110 isn't Cohn down on this list? That I don't understand. Well, he was research chemist, I guess, appointed to do research. Perhaps that was why. Cohn wee one men I was ngt able to track down. He went to Chicago afterwards, and he died comparatively young. There were a lot of people there I knew--B. S. Oppenheimer had been our own family physician for a while. David J. Kaliski I knew, Theo. Kuttner, Margaret E. rries, Jerome L. Kohn--there were a lot of very good, interesting people there. But this W@S a gpneral hospital into which you had run of the mill--not like the Institute Hospital. No. Where you controlled the nature of patients. No, Mt. Sinai took everything. We had lead poisoning cases while I was there. I had to find the lead in the urine and feces--all sorts of things like that, all kinds of problems that I never even heard of up to that time. It was very interesting. It would have meant an almost com­ plete halt in my research. Of your own work? Yes. I gether--this was the first time that you had a kind of full responsi- 111 bility. administrative responsibility. which can very easily pull you away fTom research. Well, the administrative side of it wasn't burdensome. It wee not. No. David Cohn took care of most of the reports--! mean he would go over the work of the technicians. It wae e job keeping enough techni­ cians on the job. They weren't always easy to find. We had some good ones though. Cohn would go over the reports first, and I would look at them finally after he said that they were all right and had signed them. That was about the only administration. It was not particularly burden­ some, but it was time consuming. There wasn't a calibrated pipette, or any accurate apparatus in the place when I got there. I had to begin from the beginning to calibrate all the equipment to see that accurate work was done and to update the clinical chemical methods that were being used, and that took a great deal of time especially at the beginning. It wasn't until the last five or six months I was there that it began to be possible to start to make a little research progress. It was like bringing the laboratorv then into modern times. Yes--I had to update everything that was going on there. In a verv strong sense then, while chance brought Walter Palmer to the Institute where you had f chance to get some sense of his substance end he of ¥OU whil! et the Institute •••• It certainly wee. 112 Late; on it was on his invitation to you that made the change. Yee, if it hadn't bean for our meeting at the Institute, he would have asked somebody else to become chemist. Wes it his gugqestion that no excessive burdens be placed gn YOU 80 jhat you could do vour own work. work in which vou were interested? Yes. My title of chemist to the hospital was purely a title. It didn~t involve any responsibility for any of the zoutine chemistry. That was in other hands, but a good deal of :routine chemistry was done in the Depertment of Medicine, and I kept an eye on some of that. Very often when there were questions of hemoglobin, anemia, things of that sort, ab­ normal hemoglobins, they would come to me and ask advice. Well, people said that my office was like 42nd Street and Broadway. The door was al­ ways open, and happily for me there were people in all the departments who came in and asked opinions and advice and brought their intractable • problems along. I really learned enormously up there. It was a wonderful place to be. Then going into the faculty dining room every day, sitting with different people, hearing what was going on in all of the depart­ ments, the difficulties and the triumphs that they were having--it was really a very active place. As chemist of the Preebvterian Hospital. did it then include v~nde;bilt Clinic. B bies Hospital? Yea--it was the whole complex, but as I say, that was a title and didn't involve any actual responsibility. It was just that I was avail­ able for opinions and advice whenever anybody wanted to consult me. I 113 came in contact with clinical work very quickly and very properly. Dochez wes there. Yes. Ha wasn't the only one. I bave •••• Well, Palmer was interested in the thyroid, and Dochez in strepto­ coccal diseases at the time, and joining a new department like that I felt that I should interest myself in what the other people were inter­ ested in too, so I carried forward work not only on the analysis of the precipitin reaction which was the first thing that r. E. Kendall and I did up there, but also on the chemistry of streptococci and the iaola- J•tJ Lr:-,"' tion ~ properties of thyroglobulin. That was one of the things that I went over to Upsala about--work on molecular weight. Everybody was enormously surprised that the iodine containing protein of the thyroid had a molecular weight of seven hundred and fifty thousand. What did that mean physiologically? That was a very unexpected finding. I gueae so. In terms of your own consuming interest apart from these other people who were there with interesting problems--they came in thrquqh your doar--what of vour own work; this desire to measure with greate3 pfBCision 1 or to think through and out the nature of the immune fe ■ction. There'e a certain momentum ta the field too. How does one cut across thia field in thinking about it? The first thing that seemed to be necessary wee ta get a weight of an antibody in abaolute terms, in milligrams. How much ia there in these 114 things? Nobody had the slightest idea. I mean, you had an antityphoid serum with a titer of one to a million, an agglutination titer, and an antipneumococcal serum with a titer of one to a thousand. What did these things mean? There were dreadful mistakes in the textbooks. The standald English textbook said that typhoid was a better antigen than pneumococcus because you get titers in the millions with typhoid bacilli and only a thousand with pneumccocci. Well, of courso, that's utterly absurd. I mean, you can't compare the two systems-the combining proportions are totally different in the two systems. Well, nobody had any conception of any of that sort of thing just by doing end titers. You couldn't even begin to think in chemical terms ab(,d wi IJ1o:i11 immunology. You didn't have any right to say antibodies are pro- 11 teins until you could actually weigh them. That was the thing really that bothered me the most. Everybody said, "Well, here they are coming down with the globulins." Well, you know, "What are they? Are they globulins?" We couldn't answer that question. You couldn't weigh an antibody, so how could you tell what it was. We had to begin that way. It was primarily an analytical chemical problem. Then later it became an or­ ganic chemical problem. There are still millions of them. You had Forest Kendell, He was an organic chemist. He got his doctor's degree with old William A. Noyes and was teaching at Lafayette. Noyes recommended him very highly. I wrote to a number of people and asked if they knew an organic chemist who would be interested in coming, and Noyes recommended Kendall very highly. I wrote to Kendall end said, 11 I would like to pay 115 your ax?enses coming into New York so that we can talk this thing over." He came in, and I found that he had only one hand. It developed that he had lost .one hand in a threshing machine on the farm when he was eeven, or eight years old. In spite of that, he had put all of his younger brothers and sisters through college besides getting a Ph.D. himself. I figured that if that was the case, it didn't matter to me whether he had one hand, or two. I'd take him on. He never missed it. The funny thing is that I seemed to have been fated to have one­ handed people because P.A. Rebers who was with me for six years down at Rutgers also had only one hand and he had lost his in an explosion, a gunpowder explo,ion in his basement. He had his own laboratory in his home. When he was eighteen, he made gunpowder and blew one of his hands off. Even that didn't discourage him from chemistry, and he went on to invent his own substitute mechanical hand. When he turned up with one hand, I figured that that was all right too. In broadening one's thinking about immunochemistry 1 waa Kendall imagina­ tive here too in the dialogue that ¥9Y and he had in the laboratory? Kendall--by that time I was a much less pure organic chemist than he was. He had never had any contact with biology, except perhaps a small course or two. What he did was to help me work out the details of the analytical chemical methods. Then when it came to trying to work up a theory, he was better grounded in physical chemistry than I was and also a better mathematician, although hie arithmetic was dreadful. I had to keep correcting his arithmetic all the time, but he was a very good mathematician. He took these complex date that we got and worked out certainly the simplest quantitative theory of the reaction mechanism 116 which now is a special case in one theory which is more general and is a special case of a special case in another still more general theory. Kendall's is the only theory today that the average microbiologist can use. It's still useful and simple. That in itself is •••• I mean the other theories are more rigorous--undoubtedly, but at least this guided us and described what most of our immune systems actu­ ally did, and it enabled us to make e lot of very useful end highly sig­ nificant predictions. You can't ask much more than that of any theory. I mean all of this recent work that I have done since 1955, I guess, (, on cross reaction~~their significance rests on our quantitative theory of A )kt precipitin reaction. Practically every cross reaction could either be predicted, or else if you didn't know what was chemically in your sub­ stance, it gave you a clue as to the chemistry of the substance based on the theory. 50 far we haven't made any very serious mistakes. [knocks on wood] I'm afraid someday we might. You never know. In the medical schogl itself--thinking about immunoghemistr¥--it required a different approach in thinking. didn't it 1 from what had existed there- tofore7 You meant what had existed at the Rockefeller? Even at P & 5. Put it this way--how helpful d!d the non-immunochemists at P & S regard this? Thinking about your problem. were they receptive 117 to this? Oh yes--they backed me up and gave me moral support end also when-­ well, in the beginning one didn't have the sulfa drugs to treat pneu­ monia, and naturally I was most interested in the infectious disease work that was going on except because Bill Palmer was interested in thyroid problems, I ran that as another problem along side of the other things. That was where Jacobs' techniques had helped me enormously. But anyhow, one of the first things I did up et the Presbyterian after we got our analytical method, and that took a couple of years to work out satisfac­ torily, but es soon as we had that, as soon as we could analyze sere, then we began studying antibodies. The first thing that happened was that we found that the antibody in our horse sere wee slower than ordinary globulin. We used the Nor­ throp diffusion cell and diffused a solution of antibody with a known content of antibody nitrogen against salt solution. The ordinary low molecular weight globulins came out first. The antibody came out much slower. That showed us that in the antipneumococcal horse sera that we were working with the antibodies were big molecules, and that was why I went to Upsala. Also our theoretical work predicted a method for the purification of antibodies by salt dissociation, and we got the method. It took two years to work that method out, and we got a hundred percent analytically pure antibody. It was a typical globulin, so that we had the leat link in the chain of evidence that antibodies really were globulins. From that time on then, people could begin to think about where they were formed. Since they knew what they were they didn't juat have to specu- 118 late, and could turn to what the biological processes were by which glob­ ulins were formed--nor.mal globulins--and what the difference was b~tween normal globulins and antibody globulins. Let me turn this over. We had lots of cases of lobar pneumonia and pneumococcal pneumonia. They were being typed and at that time--1934-1936--after a lot of work had been done both down et the Rockefeller Inatitute and by E. A. Kabat who tock some of my preparations over to Upsala afterwards in--when was that? in 1938, I guess that was--1937, or 1938. Well it developed from the work that went on independently and simultaneously at the Rockefeller Institute, Ken­ neth Goodner'e and Frank Horsfall's work, and ours that the horse antibodies A were mjcroglobulins and that rabbit antibodies were normal size globulins. A Goodner and Horsfall were the first, I think, to use rabbit antipneumococcel serum, and they found that they got excellent therapeutic results with this serum because the antibodies were smaller and got around. The results with horse serum had always been extremely doubtful. They had some good results with Type I, perhaps because that made the least carbohydrate, but with the other types they have never had much success with horse sere. As soon as Goodner and Horsfall started using rabbit sera, they began curing patients at a much higher percentage. That was very impressive. I immediately put a whole lot of rabbits on immunization with Types I, II, and III pneumocccci, and for several years I made ell of the purified antipneu­ mococcal antibody for Types I, II, and III that was given at the Presbyter­ ian Hospital, In general, until Squibb began purifying antibody success- Whole rabbit eera wee given, I didn't want to do that, and we knew 119 thet with ammonium sulfate you could purify globulins very easily, but we decided--Kendall and I decided that we would use sodium sulfate instead. If we centrifuged the globulin precipit~te very sharply, we wouldn't have ta dial,ze and expose the globulin to infection, or to tap water, ·or to chlorine and all sorts of extraneous influences. If we centrifuged sharp­ ly, we could squeeze out most of the sodium sulfate. If we left a little sodium sulfate in, it wouldn't hurt the people--well, on that basis I worked out a method of getting antibody solutions vary simply with sterilized so­ dium sulfate and water from the media room where the patien~a'infuaion things were prepared. Always using absolutely sterile material and heat­ ing the final globulin solution to sixty degrees because Goodner and Hors­ fall recommended it and not for any other reason, I made all of the anti­ body solutions that were used for Types I, II, and III for several years. I think that we were probably the only people who treated pneumonia adequately at that time. A patient would come in, and they would type the pneumococcus as rapidly as possible. If it was a type other than I, II, or III, they would get the purified Squibb antibody. That was very expen- \1 Id,) aive. It cost fifty dollars per hu11hwtt'a1ts, I think, or something like A that--ona hundred thousand units, or whatever they called them. I always knew exactly how many milligrans of antibody were in my solutions. We would give our pneumonia patients fifty to a hundred milligrams of anti- 1-n, == , -• /f --··-.. .---- body nitrogen as soon as the pneumococcus was typed. If .B. was Type I, II I\ or III, we would give somewhere, usually, between seventy and a hundred milligrams of antibody nitrogen. A half hour later the nurse would bring fitc .:i. CfUi Y,'- '--· .. - - . - - - , _ _ me a sample of the patient's blood, and I would set~ up with the corres- ponding polysaccharide to see if there wae still antibody there. If there was no precipitate, the patient got another bottle of antibody. That pro- 120 cess was kept up until there was an excass of antibody circulating in the patient. I don't think we lost a patient after that. People would come in moribund one afternoon, and the next morning they would be sitting up in bed asking for breakfast. We always established an excess of antibody, and that wss apparently all that was needed to cure the pneumonia. You aot this ready playback from the clinicians, didn't xoy? Yes. This was all done in cooperation with the clinicians--Yale Kneeland, Jr., and Joseph C. Turner. I was right in the midst of the clinical work and then--well, with the patients, I guess, who had other types, it depended. They never asked me to see whether there was an ex­ cess of antibody or not. They usually had to wait until the next day to see what the clinical condition was. Sometimes, I guess, it was too late. We had one man who had had a mastoid operation. They were still doing mastoids then, and we isolated a Type III pneumococcus from his ear. He came down with a terrible pneumonia, and they assumed that it was a Type III pneumonia, and they said, "Well, have you got any antibody?" ,,..,----""'-. We gave ~ a bottle of antibody, and it disappeared immediately from the serum. In a half an hour there wasn•t a trace of antibody left. It took five bottles of antibody to establish an excess of antibody in his case. By the time we had gotten to the third bottle, I thought that the patient must have some mechanism for destroying rabbit protein. I had a horse serum against rabbit globulin, and he was still full cf rab­ bit globulin, so that it was only the antibody that would disappear. The pneumococcal polysaccharide in his lungs and in hie whole system, I guess, was just getting rid of the antibody, and it took five bottles of antibody before he got well. 121 You could see the relevance right away. The what? The relevance of the work that you were doing right away. Oh yes, of course. Then another clinical development like that was when Dr. Hattie E. Alexander at the B ,:bies Hospital was working on influenzifmeningi tie in u:er-e children where there was ninety percent mortality. There,._~- some horse II sere available which had very little antibody in them. One of my former students worked with her on isolation of the polysaccharide of the influ­ enza B bacillus which was causing all the trouble. We analyzed the sera that were available, and they only had about a tenth of a milligram of antibody nitrogen in them per cc., and so I said "I think if we use the same principles we used in immunizing rabbits with pneumococci, we ought to be able to do much better than ninety percent mortality." Well, we jocked up the antibody content with proper courses of im­ munization to a milligram and mora per cc. in most of the rabbits, and then we purified the antibody the same way we'd been doing for the pneumococcal antibody. She began giving that, and the mortality went down right away from ninety percent to five percent. Junt at that time when we knew how to take care of our pneumonias _j and were getting excellent results with ths influenza~meningitis ,1 the sulfa drugs came in and penicillin. Then y8u didn't have to type pneumococci, I or use serum for the influenza~meningitis. A At least the sulfa drugs did as well in the spinal column of babies as serum did, and the mortality was no higher with the drug alone. The sulfa drugs and penicillin didn't 122 know the difference between the pneumococcal types so that we didn't have to type pneumococci anymore. We we.re just handling the problem in a really scientific way when it no longer became necessary to do so. Quite apart from that you learned not a little about the immunization process too. Yes. Well, then came the problem of whether or not human beings could be immunized with capsular polysaccharide. I had a whole--well, that was done for the Surgeon General of the Army. They had a camp out in Sioux f lls where there had been epidemics of pneumonia for several years. They had a team of people out there studying these epidemics of pneu·monia, and they knew exactly which types were the most frequent and (li_CS{ cj were causing·- af:f:the trouble. They wanted to know whether they could '\ stop these epidemics by injecting pneumococcal polysaccharides. felton's work unfortunately hadn't given the answer because, as I explained earlier, he had had hard luck with his controls. Also his analytical data were based on mouse protections, and they varied between zero and a million units. You couldn't interpret anything like that be­ cause by that time we knew that a thousand mouse protection units corras­ ponded to about a milligram of antibody nitrogen. You couldn't have a thousand times that much in any serum and have it circulating. It would stand still, so they didn't know what to do. The war was on, and they asked me if I could do something about it. Well, I said, "I'd try if I could get medical student volunteers." This was when they had that terribln accelerated medical program, the three year program. It was driving the students half mad anyhow-- they w2re workinQ so hard. In spite of that, I had more than a hundred 123 C,LJ k ,c· ' G -z ( (_ of them volunteer. I went up into the anatomy laboratory, gCJI held cf e s J::~~ first year student'; 'told them what I wanted to do, and more than a hundred /\ of them volunteered--practically everybody in the class. We started in with too little polysaccharide first and then increased the dose, and we found that the response was highly variable. There were a few severe reac­ tions, but I didn't give too much at a time so that nobody really suffered very much. We got quantitative data showing that, in general, you could get an antibody response. Most people responded to one or another of the mixed polysaccharides that we injected. Well, that didn't tell whether they were protected, or not, against pneumonia, and you couldn't ask these people who were studying medicine to be sprayed with virulent pneumococci so I wondered what the dickens to do about that. Just at the right time a paper appeared by Barry Wood dmm in Johns Hopkins that he had sprayed rabbits ~Jith Type I pneumococci .~-~·- and then--not rabbits, rats--JS==i&twelve hours later he had injected a certain antipneumococcal rabbit serum which, he said, had five hundred thousand units per milligram. Two hundredths of a cc. cured them and two thousandths of a cc. failed to cure them. I went and searched the litera- ture for the blood volume of rats and found some figures. I found that the average response that I had gotten was about a third of the amount-­ in the first place, I had to get the serum that Barry Wood had and find out how much antibody was in it. Luckily he had some and sent it to me, so I did an analysis on it and found out how much antibody was there. I figured that an already established infection in rats could be cured with three times as much ea my average antibody response was in the students, so that if you could cure an already established infection, about a third as much ought to be enough to prevent a droplet infection--or whatever the 124 method of infection is because it haa to start very small. I recommended on the strength of that that this immunization really be tried. The next fall then we got polysaccharidea partly from Dr. Augustus B. Wadsworth up in Albany, partly material that I had, and partly some that Squibb had made especially for this project. Tha field people who had been out there et SiouK Falls and in the aviation camp recommended that we try immunizing against the four types that were responsible, or had been responsible for the three previous years for about sixty percent of the cases of pneumonia. We made up a mixture of these four polyeec­ charides, and in September when twenty thousand cadets went into the Avi­ ation Training Center, ten thousand were lined up on one side and given a cc.of salt solution, and tan thousand were lined up on the other aide ift.., rn.-d,'c·S: and given a cc. of the mixture. Thel'l1ti.;)' .. /'; eat back to see what would happen. During the first two weeke in the immunized group there were two cases each week of pneumonia due to the types that we had immunized against and after that for the whole study period, more than eiKtaan weeks, there were no more c&ses. We knew that it would take at least two weeks for the antibodies to come up properly. That was all right. Than we had, as a further control, the fact that we had only immunized against the types that were responsible for sixty percent of the cases. Well, the types that we didn't immunize egainst--the number of ceaea was absolutely the same in both groups. That meant that the infections were purely random. We alao had a further control because of the types that we did im­ munize against in ti a aat::m:un,asd ;1111:ip. there were only half as many ~~ H; y,._1~-~i~ t :/ ~; C'-' ~ cases_l\as had been expected. That was a puzzler, but the people in the 125 field found that the immunized group of half the canp population were no longer ~•rrying the four types that were responsible fer sixty percent of the infection and that ramcving half of the carriers pmtected the people who weren't immunized, in pert, too. We had this double control, and I think that made it one of the best controlled epidemiological experiments in medical history. It's the sort of thing you can only do once because now that we know that it's effective, you have no right to withhold it from the forty percent that have other type infections. We know now that ,;11 '.!-111.;d> in any closed population ~~■ Nl-there•s an epidemic of pneumococcal pneu- monia, once you•ve determined the types you can atop the epidemic within two weeks with the polyaaccharides. Well, the question came up then too whether one should immunize the general population. They thought in the beginning that they would do that, and a lot of my friends started injecting the Squibb solution i:o::=e d*l lfnr of six, or eight polysaccharides for adults with the types that were most frequently in adults and another solution for children. Our recommendation was that they give only three tenths of a cc.of this one cc. mixture first to eee whether people were sensitive to it• or no\ be­ cause we found quite a few that were sensitive. Most people were not willing to come back to the dcctor~l\0ii;,,or injections and throughout the country they had some very severe reactions and decided that it was too dangerous, and besides, the possibility of any one person getting any one type of pneumonia was a rather small one, so there is really very little need to immunize the general population. Now there's a movement on foot to start the whole thing up again. Dr. Austrian ia convinced that a lot of old people die because of the strain put on their hearts by the pneumococcel infection and that the 126 sulfa drugs don't always work. There are resistant strains. Some people are sensitive too, of course, to penicillin and he thinks there is a real need now for immunization especially among the elderly. Somebody over at the Lasker Award dinner said that there wae some­ thing in today's paper about pneumonia vaccination. I haven't seen it. Th@ last page of the firat section. Was it about Austrian end his work? The car I rode in on on the train--the lights didn't wc,rk. I'll see it tonight, if we don't play too long. Well, that was just some of the direct, practical work that I got involved in. On what basis did you make the mixture? Of what? Of the polysaccharides. You mean out there at Sioux falls? The people in the field had found that Types I, II, V and VII had been responsible for sixty percent of the ceses, and we knew that you could safely inject four to six without getting reduced antibody responses, and so we decided on the four types that were responsible for sixty per­ cent of the cases, thought that we would hit it somewhere around fifty percent end that would give us a better measure of whether it was any 127 good or not. There are 80 manv loose factors th9t come into the pictuJ•• What about the variability in human reaponpe to this? Well, we thought about that a great deal. Occasionally we would find somebody who would give a whoppingly good response, sometimes en amazingly good response, showing that these were very powerful antigens in human beings. We always went back in their histories to see whether they had had a previous case of that kind, that particular type of pneu- 8. It a,~ ll~·1i,~. ~ mania and that this was some kind of .•nsa ♦ ,e reaponse,,'\the immunologist ,JILd("l'lcS-/ ;<! ...__..---~···~-~~ says. There is no .am ■■ •ic response with polysaccharides. You get a maximum, and it lasts tremendously long--for a period of years, whereas with diphtheria toxaid and protein antigens, it goes up high and comas down very fast. I think the reason the response laets long probably is that these polysaccharides don't get broken dawn in the body. They hook on to a cell somewhere and the antibodies are made to them. If the cell dies, the polysaccharides get out in the circulation and hook on to an­ other cell somewhere. They are probably as permanent as life itself. Yes, their durability. Well, the response goes down very slowly. The longest measurement I ever made was eight years after immunization. I haven't had anyone who has gone longer than that. Then the antibody was still about half rl\cltl •5 '-----y----' of what it was in the beginning, so ~turning out, turning over anti- body all the time, making it, destroying it, and making it again all the time for eight years. It's still going on probably--still at a measur­ able level. 128 A powerful force. Yes. Well, we had some interesting work with R. Schoenheimer too. Schoenheimer was the first to use heavy nitrogen in biological studies. As a result of his work on the metabolism of proteins, he thought that amino acid bonds in a protein kept opening and closing all the time. If he fed an amino acid, it would shoot into a protein very fast, and the only way he could explain it was that the bonds of the protein would open up end the amino acid would go in and replace an amino acid that came out. Well, we thought we'd like to check that immunologically. Thia was a very good idea that H.P. Treffers had. We had a rabbit that we had immunized with Type III pneumococci, and we waited until the antibodies were at the peak and were beginning to come down. We didn't give any more injections end then we injected a very strong serum containing Type I antibodies from another rabbit and then we started feeding heavy nitrogen. Only the Type III antibodies took up nitrogen and not the ones that we had marked as Type I from enoth~r rabbit. It was only the new protein that was being made that took up the heavy nitrogen. When Schoen- lveh. ~ heimer saw those results, he said, "Dy~•" He had to abandon the idea, but this was the first time that an in­ dependent check had been made with another kind of marked molecule so that his error was understandable, but we showed immunologically that he ~,as wrong. That was one of the early things that we were able to do with quantitative immunochemical methods. You kept up the relationship with Avery, didn't you? Well, we didn't publish anything mere together after I left. We _j. 129 remained extremely good friends. He continyed hi; work in pneumonia. Yes, with W. F. Goebel he continued working on the chemical aspects \/<.ll'Jt'd\t~ .............. -- "J_,_ _ _ of it. They went off mostly on the synthetic "•xi ■ MG&f and they showed that the sugars ware an extremely sensitive tool for immunological re­ search because even turning one carbon around in the sugar was enough to change the specificity. They showed that very clearly. That was a beau­ tiful series of papers that they published. Then Avery would come and talk about hie work on the transforming substance too, and he was fully aware of the tremendous biological signi­ ficance of that work. There was something that told him that this trans­ forming substance wee something that really was fundamental to biology, to research in cancer, and to the understanding of life itself--that this DNA hed something to do with it. He realized the importance of it, but it was strange that it took so long to catch on. Avery should have had the Nobel prize for that. J~, ,l'e (J(l{'J cr:::.:;..-,-- What was this introduction, this fg 1 ~ to this nucleic acid symposium, ilYewcrd '·"·······~ this conference et Rutqers--the f:SPUG9 where you said that :,:ou had had DNA in your hand. Yes--well, we didn't know whether it was DNA, or RNA. It was pro­ bably DNA--oh, yes, it was DNA. It was not sensitive to ribonuclease. Yes, it was DNA. That was part of the streptococcus work. I still think that we had a very good way of fractionating streptococcus, but it wasn't ae good as Lancefield's. We never had a fraction that was purely type specific. It wee always a mixture of group specific and type specific. 130 T That {;j protein was the funny one--and the~ protein. You've alreadv mentioned in passing Upsala and vaur trip over there. This was in 1934 and again in 1936, on the--well 1 Henry Allen Moe's foundation. The Guggenheim foundation--yes. Yes, but the equipment that had been developed. You found this equipment very useful at Upsala, and it was the only one of its kind at that time. Yes. I think that's worth a word and particularly the people who were very ie­ eourceful and very helpfyl to you. Yes, well actually what happened over there was--this was in 1934 with thyroglobulin. That was the first time I went over, but the thyro­ globulin problem was infinitely more simple than these immunological ones ,per because it was just taking a\~fused gland and isolating one of the not .I too many components from it. We got relatively pure thyroglobulin. 'W took it to Upsala and made some more over there and in six weeks we had the answer. ~ The .ll:ll¼!t: reason that we got the answer~was that T. Svedberg a ■ signed his young associate K. O. Pedersen to me as he had done with all the foreigners who had preceded me. Pedersen for six weeks did 1U1a~9 - practically nothing but work with me on this problem. I felt that I had to include him as a co-author on the paper that we published afterwards. Well. nobody had ever done that before for some strange reason. They had always said, "Our thanks go to Dr. Pedersen without whose assistance this work would have been impossible", but here was a man who was giving up his own work to be decent to a visitor and make it possible for the 131 visitor to do something in the time thet he had available, so I felt that it was simple decency to put his name on the paper. Well, after that, of course, everybody else had to do it too, but I don't know why it wasn't done before. It seemed to me a lack of some kind of moral feeling. The actual equipment itself--well, there were certain modifications to it by A. Tiselius. Oh, the Tiselius apparatus came somewhat later than the ultracentri­ fuge. The ultracentrifuge was just this terrific speed of whirling around that twirled the heavy molecules faster than the lighter molecules. If a you used ultraviolet light andrprotein solution--Svedberg designed his A cell so that you could shoot light through it as it spun and get a picture. You could see the boundary going down, and the rate at which the boundary went down and the temperature end half a dozen other correction factors which required Pedersen's help unless you wanted to study for a year or more--all of these things made it possible to get valid measurements of molecular weight. It was really a terrifying piece of equipment because the whole in­ stitute had to be built around it. The centrifuges were down in a base­ ment, and they had a huge sheath of protective concrete around them in case anything blew up, which happened occasionally. They had to be run in e vacuum, end you had an enormous panel on the wall with huge gauges-­ just like the engine room of a ship. It was exactly like the engine room of a ship, and there were a half a dozen gauges that had to be watched continually. Then you had to go and take a photograph every few minutes. The first time I was left alone with this equipment which was the second, or third time that we made a run, I was just terrified. I didn't know 132 what was going to happen. .:Cda --~·,-.-, Pedersen--my wife and ~ Pedersen got to be very good friends, and Kai and I got to be very good friends. We have been friends all our lives. Whenever they come to America they stay with us, end we always visit them in Upsala whenever we go to Sweden. It was a nice episode. Tiselius was there one of the two times that we were there. What were his modifications •••• Ole. ~ It was Lamm-~ Lemm who devised the optical system to the ultra- centrifuge and who was responsible for a good many of the physical chemi­ cal calculations. Tiseliue was the one who worked out electrophoresis and made electrophoresis a practical tool in biology. That was a tremen­ dous step forward. How do you account for •••• Well, we've been good friends too ever since. Was there something peculiar about Upsala and these people who made these advances? I guess it was Svedberg who wae a genius, in that respect, and who gathered original, competent people about him, and they just made these two tremendous steps forward within a few years of each other. Well, Svedberg had the ultracentrifuge quite a few years before Tiselius had developed his electrophoresis apparatus. Then, of course, Jesse W. Beams and the spinning top--that wae another enormous improvement that made it possible for almost everybody who could get a grant for fifteen, or twenty thousand dollars to have an ultracentrifuge, whereas up to the __J 133 spinning top era, you had to have a whole inatituta if you wanted to have an ultracentrifuge. That wae a major thing. When I came back from Upsala, one of the foundations offered me an ultracentrifuge, and I declined the gift with thanks. I said that I didn't want to be a slave to the instrument. I still had immunochemical problems that I wanted to eolve--to use the ultracentrifuge whenever necessary, but not to preside over ona end spend all my time being the slave of an instrument. Yes--watching those dials. That was before the spinning tops came along. I saw Beams in Phila­ delphia at the American Philosophical Society. He got the national medal last year too. I've seen more of him these last two years than ever before. Well, was Tieeliua working on an immunochemical problem far ¥Ou? No• this was a purely physical chemical one. He was always inter­ ested in biological applications of physical chemistry, end his great ad­ vance was in doing the electrophareaia at four degrees where the density of water is maximal so that if you have e slight fluctuation above, or a slight fluctuation below, the differences are in the same direction. That was the one point in the temperature range of water at which you have the greatest stability. Nobody had ever thought of that before. Well, that made all the difference in the world between something that was unpredictable and something which could be controlled end 134 handl•d and efficiently kept at that one temperature. You could see dif­ ferences between the speed at which different proteins move. Then P. Graber and C. A. Williams when they combined that with immuncdiffusion-­ that wee another stroke of genius. Immunoelectrophoresie, another big step forward. I was very proud to have given Grabar his start in immuno­ chemistry. He was from--whet is it?--the Pasteur Institute. Yea, he is now retiring--hae retired as Director of the Institute for Cancer Research. He held two jobs, part time at the Pasteur Institute the last years. He came and worked with you at Columbia. at Presbyterian. Yes, in 1937. It's strang~ how the existence of a tool like the ult.acentrifuge can be used and in the hands of someone who can make it sing for its pyrpose •••• Yes. It cen shed light on your own problems and give you data wheJe none had existed before. Yee, and electrophoresis hes done the seme thing, so that we're ell very much indebted to the Upsala people. I'll say. Then the knowledge that you gain has such great utility too. There's a certain continuity in periods of stress--war time. the fact that you uproot people. move them around where you need production, or 135 whe.e you take young men in from all walks of life and suddenly have them in barracks and the question of air in barracks--how to sleep, I never dreamed when I wae in the Army the kind gf questions that were being apked by the Army Epidemiological Board--vou know, where they really didn't have information. No, they didn't. Dr, Dingle'@ eet up in Fort Bragg for upper respiratory diee1ses and the grpat possibility of variety in this. Yes. Staggering when you stop to think of it and especially when you're study­ ing it, and you seek that general!zation which will edd to your control knowing that there are variations in the picture also. It's tremendous. There were other war problems that I was mixed up with too. Upealp--didn't you send one of your students there? Yes--Kabat. He got a Rockefeller Fellowship after he got his doc­ tor's degree to go over there. He took samples of our purified antibody solutions with him and made others over in Upsala, and he worked on those. They showed that there were these two classes of antibodies with low molec­ ular weight and high molecular weight, that some animals produced one kind and some produced the other and some produced both actually. That didn't come out of that work though. It now looks as if most animals produce the high molecular weight ones first and then the low molecular ones after­ wards. 136 It'e a slower procegg? Yes, and the reeponsa a ■ems to be feater at the higher ones, but sometimes it just keeps on as the high molecular weight ones. The funny thing now is the most recent paper on antibody molecular weight by Joel W. Goodman--one of Kabat•• Ph.D.'s is doing very nice work out in Calif­ ornia--in which he claims that moat of the antibody in horse aere now, antipneumococcal antibody, is not of high molecular weight, so either the horses have changed, or the antibody has changed since then. He got very definite results that can't be laughed off, but I think it's possible that in some of the old aera that we•re uaing the antibodies have gotten partially degraded by enzymes that are present. That•s one possibility. Goodman claims that the results of one of his moat recent sera in horses are mostly low molecular weight. Well, whether that's an exceptional horse or not, I don't knew. It gives you pause though. Yea. Well, anyhow, the horse antibodies were the first recognized ~-a mlcroglcbulins. l mean they were found independently to be large mole- cules in two laboratories. Goodner, Horsfall and Johannes H. Bauer did it in the Jesse W. Beams ultracentrifuge. We did it first in the North­ rop diffusion cell and then confirmed it over at Upsala, so that there couldn't be any question about that. Lots of antibodies are continually a still being found to be big molecules, mTcroglobulins, but the thing that I find strange is that Goodman's work shows that et the present moment the horse antipneumococcal antibodies that he examined were not big ones. It•a hard to explain. 137 Then I think another confirmation that we had was that as soon as they sterted using the smaller rabbit antibodies they got e much better therapeutic result too. It wasn't only a question of shifting from one animal to another--the horse is es close to the human as the rabbit, I guess--perheps closer. Well, there was much less serum sickness too--they used to use whole e horse serum and that was terrible. You "iould have terrible serum sick- ness after getting diphtheria antitoxin too. Yes. You said that the laboratory was like Fortv Second Street, and mev- be the association of a name will suggest something. 1isc -....-,--:- 1 knew Alwin M. Pappenheimer end his eon, Maurice N. Richter, Homer /1 D. Kesten and his wife, Arthur P. Stout and Virginia K. Frantz, and it was at Virginia Frantz's suggestion that I did a piece of work on oxi­ dized cotton • .Qid you? Yes. They were using oxidized cotton ea a hemostatic for one thing and as a packing that could be left in wounds. It wasn't like regular cotton. If you forgot to take regular cotton out and sewed up a wound, then it always caused trouble, You had to open the wound up and take the regular cotton out again afterwards, but with oxidized cotton you could leave it in the wound. It was acid for one thing, and it acted as a hemo­ static, The body fluids neutralized the acidity very quickly, and then it slowly began to dissolve. Well, the minute I read a paper in the Hournal of the American Chemical Society on oxidized cotton, I knew they had changed insoluble cotton into a soluble polyeaccheride with the 1 138 specificity of Type III and Type VIII pneumococcus. It was our theory that enabled me to predict that. I sent to Eastman Kodak for some oxidized cotton and got some of that material. It gave immediate precipitates in Type III and Type VIII anti­ pneumococcal serum as predicted. Well, then I found talking to Virginia Frantz, I guess at lunch one day, that the surgeons were beginning to use this stuff because they could forget it. It wae the only material that they had found up to that time which didn't cause trouble in wounds. Any­ thing that was left before would always cause e granuloma, or irritation, and it would have to be taken out eventually, but this stuff, this oxi­ dized cotton, could be left right there. It stopped the blood flow, could be left right in the wound, and it would eventually disappear. They tried it on many animals, and it was very good. I said to Virginia, "Would you like to know how long it lasts in a human being?" I told her about this cross reaction, and so they began sending me i;,,.,o f ,d t'Led, blood samples and urine samples of patients who had had pieces o~;cotton left in them. I got beautiful precipitin reactions both in the urine and in the serum of these patients. I could tell them almost within the hour of the time that the last bit had been dissolved. That was another im­ mediately practical application. Of cqyrse. It's marvelous in a wav--better then a who done it. isn't it? Yea. It really is. Well, Gladys L. Hobby was in microbiology then, and we tried to see 139 if you could protect animals against Type III and Type VIII pneumococcal infections by immunizing them with oxidized cotton. We couldn't do it. I think the reason was that the cotton had bemn so depolymerized in the course of the oxidation that it was no longer big enough to be antigenic. The molecule had been degraded so. It was big enough to have multiples, 5 so you could get precipitat~n vit;o if you had the antibodies already, 'I but not big enough to be antigenic in its own right. I've always wanted to see if one could oxidize cotton much more gently than they did industrially. The stuff had no more viscosity. These pneumococcal polysaccharides which are long, thread-like molecules give you a terribly viscous solution and oxidized cotton ought to too, but it gets chopped up too fast. I'm sure, if one could get a big enough oxidized cotton molecule--perhaps if you could take the commercial pro­ duct and .fractionate it, you'd find that part of it was viscous and large, maybe one percent, or so, and I'm sure that would protect. Anyhow, that was another amusing little by-product. But you couldn't get it to work in animals. Not as an immunizing agent, but I'm sure that it was depolymerized too much. This was eoraething that she brought in with her. ~ ~-.'.~'.i'.~~~ Well, IHB!! was working on the animals and--sae. was in surgical path- th.e ology, and it wasTpathological sequelae of things that were left in wounds which started this whole problem. Whether the surgeons still use oxidized cotton or not I don't know. Well, I think I'll go home and take a nap. 140 fridav 1 November 22 1 1968. In ell the catalogues I've been able to find. vgu're listed in two places-­ one is the Department of Medicine and the other in the Biochemistry Depart­ ment on leave, I think it is 1 or rather "assigned to" the Department of Medicine. Yea. What's the story here? Well, it just seemed to me with all the biochemists around P & S that for me to have the title of Associate Professor of Medicine without even an M.D. degree was sort of misplaced. I just voluntarily asked them to change my title to Associate Professor of Biochemistry assigned to medi­ cine. I felt that that was more descriptive, but it resulted in my being really under Professor H. T. Clarke's jurisdiction. The funny thing was the difference in the way in which these two men ran their departments-­ Bill Palmer, who was Profeeaor of Medicine for the first half of my stay up there at P & s, used to have a meeting of the whole Department of Medi­ cine in his office once a week. After lunch everybody would drop in and talk over current problems, or if you had anything whatsoever to say, you were welcome to aay it there. The whole twenty-seven years that I was up at P & S, Hans Clarke called only one departmental meeting. This voluntary change was probably the reason I was an Associate Professor for fourteen years. There was political bargaining back and forth among the biochemists of other departments, and I waa more or less a victim of that political bargaining until some of the other people got 141 . ±;::_,t what they wanted. Dr. Palmer put me up long before I actually got my I\ full professorship. Foi records you were under the Biochemistry Departmegt. Yes. For actual work you were under •••• I was always physically in the Department of Medicine there up on the medical floor. What teaching did vou do? Waa this right away? I gave the last two lectures usually in the biochemistry course-­ one on chemotherapy end one on immunochemistry. Also usually I gave one or two lectures in the course on microbiology. At one time when Dr. Treffers was up there with me, he started e course, a more or less grad­ uate course in immunochemistry, end I gave half a dozen lectures in that. Of course I had one or two graduate students at a time and did teaching that way. That was all the teaching really. Most of my time was spent on research. Yes. this was the original design that Palmer had. Yea, and it was generally understood throughout the whole medical school that anybody, who had any problems that they thought I could help them with, was welcome to came and talk about it. A great many of them did. That's why people said that they thought my office was like 42nd Street and Broadway, but I learned an awful lot from that. It was really a rare privilege to have people want to come in and talk about their 142 problems. I heard all eorts of things, and when I finally went to Rut­ gers--that and the faculty dining room were the two thing• that I missed most, the medical school atmosphere with all its problems and hurly-burly and the talk in the faculty dining room. We didn't have anything like that down at this small Institute of Microbiology. You mentioned graduate students who worked in the laboratory with YOU for graduate work. Yes. Were they local beY!• or •••• Yes--well, at that time there weren't any fellowships available for them. What we usually did was just hire them as laboratory helpers. They could take all the courses they wanted. They had to do the routine work of the laboratory, take ell the courses they wanted, and when they were ready to start a research problem, we let them do it. Tha first one that I had--well, we had several laboratory helpers, Kendall and I, before Elvin Kabat came along• and it was very interesting the way we got him. I don't know whether you're interested or not. I want to know about your student,. It's just a detail--well, my wife had a dressmaker. Somebody had told her that there was ■ Mrs. Kabat up in the Bronx who made dreaaea very well and sold them very reasonably, and it turned out later--well, I learned that her husband had chronic leukemia, and she was keeping the ~K family going by dressmaking. Once when my wife was up there Mrs. iabat said that she had a very brilliant son who waa just crazy about chemistry, 143 that he was going to get his B.S. that year at City College, that they couldn't afford to send him to the University to do graduate work, that somebody had told her that I was a chemiat, and did my wife think that there might be aame chance for him to work in my laboratory. Well, it just so happened that we were about ta lase a laboratory boy, or we had last a laboratory boy, so I said, "Send him along." We liked him and gave him the job. He hadn't been in the laboratory more than a couple of weeks when he had read every one of our papers which weren't so very many at that time, but he knew and understood, of course, with hie background. City Collage is very good. Ha knew exactly what was going on, and he said, "Why don't you apply your new quantita­ tive method to bacterial agglutination?" I said to him, "We've always had that in mind, but we're still try­ ing to clear up the details and make the precipitin method more precise. If you're interested in bacterial agglutination, you go ahead on that." That was the way he started, and actually bacterial agglutination wasn't what he did his dissertation on. He got through with that long before he was ready to get his Ph.D. degree. I put him on another prob­ lem for his actual dissertation, but before he left the laboratory to go abroad with our antibody preparations he'd already had six or seven publi­ cations with us. The main difficulty with him was to slow him down. He was really a terrific dynamo, and he had to be slowed down so that he would do everything thoroughly enough before he went on to the next thing. Well, he's had a very remarkable career, and I'm awfully proud of him. My next Ph.D. was Manfred Mayer whom I also got from City College, and he worked cut awfully well. 144 A creative fellow too. As for Kendall who was my first co-worker up at P & 5--whan he had been with me about four years I applied Dr. flexner•s reasoning and said that as long as he stayed with me his work would be known as Heidelberger end Kendall end not Kendall's work and that he ought to look around and start standing on his own feet end get an independent post somewhere. Just at that time the greet depression was on, and the war also--well, no, it was before the war. It was the depression that kept Kendall from getting a good job. He stayed with me for eight years. I told him that I'd love to have him stay as long as he wanted to, but that for his own good he ought to look around. We were together for eight years before he found a suitable opening, and he's done very well at Columbia. He went to Goldwater Memorial Hospital with the Columbia group there and un­ fortunately left immunochemistry to work on arteriosclerosis which was the chief problem down there. Do you remember your other students? Yee. I had another one from City College--Harold Markowitz. He is now at the Mayo foundation. He went out to Colorado--no, to Salt Lake City, to Utah, the University of Utah Medical School and did very well there. I don't knew why he finally decided that he ought to get an M.D. He was one of the few people who had his Ph.D. first and then got an M.D. He wea in the Department of Medicine there at the Utah Medical School, r~ in w,introbe•a '-'---' Department. Then another student I hed was one cf the bright boys from the High School of Science. We uaed to take them when they graduated and keep 145 them until the draft got them during the war and this one, Myron A. Leon graduated from the High School of Science et sixteen. We took him on as a laboratory helper. He was really too young to be a graduate student and he bagan--he really was very bright and understood everything that was going on. He began exceeding his authority, and I final.ly had to throw him out. A couple of weeks later he came back very much ch•stened and asked it he could start all over again, and we let him do that. When he was eighteen, he waa drafted into the Navy. I called the Admiral in charge down there at the Bureau of Medicine and Surgery and said, "We have a very bright young scientist who has just been drafted, but you ought to use him in some scientific aspect of the Navy's work, if you could." The Admiral made a note of it, said that Myron Leon would have to go through the regular boot training in upstate New York somewhere, and thet then they would assign him to a job. They made him a pharmacist mate, and ha was assigned to St. Albans Hospital where we did our malaria work afterward. Than after the war, he came back as a full time graduate student and got his Ph.D. with me. The graduate work--was this in the school of medicine? Yes, in the School of Medicine. You could get chemists who didn't require the M.D. degree and the school could give a Ph.D. in chemistrv7 Y ■■ -w■ll, the Ph.D. waa given by Columbia University. We always had to go down to the main campus for our Ph.D. examinations, and every- 146 one--all the professors in tha whole university had the right to attend any Ph.D. examination. That was fatal for one of my students. I had a man named Herbert E. Stokinger "'10 had come from out west somewhere. He did a very good piece of work with me on thyroglobulin, and when it came time for him to take his oral examination and defend hia diaaertation, he started out beautifully. Everything went along very well until Pro­ fessor Victor K. La Mer, the Profeesor of Physical Chemistry wandered into the room. Well, he hadn't bean specifically invited, but he was attracted by the title of the diaaartatian, thought that he would come in and listen and see what it was all about. Well, the minute Stokinger saw somebody that he didn't know, he ~ pani~ed. He thought that "maybe this man is here to flunk me", and he couldn't answer anybody's questions at all after that. We went into a huddle about what to do for him, or with him, and we decided that he was to have another chance. L■ Mer was to ask him a question, or two, and one or two of the microbiologists who hadn't gotten around to asking him anything were to sit in on it and eee whether they thought Stokinger was a suitable candidate for the degree. The aecond time around Stokinger knew what wee coming, and he went through all right, but it was funny what an effect that had on him. Changed a variable. Yes. When I first went to Columbia the head of the Microbiology Department, Bacteriology, wee Frederick P. Gay. He was a rather pictur­ esque character who had worked with Ehrlich. He was very sympathetic to the chemical approach to immunology and quite anti-Bordet. 147 ~Jas he? Yes, but in 1947, when I wee asked to go over to Paris to the First International Congress that was held in France after the wer, Bordet was there too, and he gave a marvelous talk. I was very much impressed with both Bordet'a book and with Bordet himself. I have undertaken now to write a chapter in French for Paul Bordet•s modernized version of the Treatise on Immunologv. This was old Jules Bordet, his father. Somewhe.e along in herg--I don't femember the ex1ct date--you put out a textbook on immynochemistry. No, I never wrote a textbook on immunochemietry. At Robert Loeb's urging I gathered together some lectures, and in 1956, published a book of Lectures in Immunochemistrv [New York, Academic Press, 1956] 150. That's the smell book of lectureg. Yes. They were given •••• In Japan. In Jepan--yes. I don't think that's the work I have in mind. Well, the only other book I have ever written was when I thought I would be looking for a jab in the l920's, and that was an advanced labora­ tory manual of organic chemistry. I remember thet book. That was published really, I guess, because K. G. Falk w,a was e 148 biologist, a microbiologist in the City Laboratoriea whom I'd gotten to know through Dr. Williem H. Parka' work, was on the Board of the Rhein­ hold Publishing Company, and ha recommended ta them that they take this little book of mine. Thip is an introduction, reallv--n9t a book. an introduction to the Annala of the New York Academy of Sci;neea• book on immynoch9ia}r¥• Oh--that wee a symposium that I organized for the111. That was just a symposium in "'1ich Kendall :really gave the chief talk on immune reac­ tions. He put forward there• statistical basis for the strange curve that toxin& and antitoxins showed in their precipitating behavior. I don't know that anyone has ever found fault with it, but nobody has ever adopted it apparently either. Then I ran a few other conferencea--one on immunochemiatry for the Office of Scientific Research and Development at one time. Was it during the war, or shortly after the war? Another one was the National Academy of Sciences Conference on Complement which was very intereating because they ware organized-a whole aeries of expert's conference• were organ­ ized by Duncan A. Macinnes whom I knew very well et the Rockefeller In­ stitute, and he wanted the Academy of Sciences--the New York Academy of Sciences to have amall conferencea of experts instead of having the whole membership invited to every conference that they had. He wanted a new kind of conference to diacusa work in progress, important subject• that were being worked on end where the evidence was aa yet not conclusive and where new ideas needed to be sought. Maclnnea tried to get the peo­ ple at the New York Academy of Sciences, of which he was actually presi­ dent at one time to work an this, and he wae very strongly opposed by the 149 Executive Secretary, Mrs. Eunice T. Minar, who claimed that the charter of this society provided that the whole membership would necessarily be invited to all conferences. I don't know whether the dispute could have been resolved by amend­ ing the charter, or in some other way, but anyhow, it ultimately led to Maclnnes's resignation from the New York Academy. He went on to push this idea at the National Academy of Sciences to which he had been elected some years before that, and he had several highly successful conferences on various physical chemical problems, just small conferences of twenty, or thirty experts in the field. They found a place out on Shelter Island, a small inn where they could get very reasonable rates during the week-­ it WRS always crowded every week-end, but during the week they made spe­ cial rates for a small conference, and eventually he asked me to organize a conference on the complement which was in very active ferment at that time. I got together people like Dr. Severo Ochoa, who had never even heard of complement, another physical chemist from the University of Wisconsin--Robert A. Alberty who is now Deen up at Massachusetts Tech end was Professor of Physical Chemistry at Wisconsin, but at that time he was just a young assistant professor, I guess, if he had even gone that far. I also got together several other people from the fields of enzyme research and other branches of research who never before had been ex­ posed to complement research. There were about twenty-five of us, and we spent the first evening out there with those of us who had actually worked in the field discussing what we thought we knew about complement. Then all the rest of the time was spent on what we didn't know and what we needed to do to find out what we didn't know, and it was really a very exciting and stimulating confrrcnce. It resulted in Alberty and BBldwin 150 writing a whole new theory of homolysis which was wrong, but which was e new idea and stimulated a lot of discussion. It really was very helpful, I think, so Macinnes went through with his idea and had a lot of very pro­ ductive conferences as a result, under the auspices of the National Aca­ demy of Sciences. Of the theories •••• Nothing was published, except a report in the Proceedings of the National Academy. I wrote a report of the conference for the Proceedings of the National Academy, and that was the only publication that any of these conferences had. Each chairman was supposed to file a short report of what went on. These conferences were really very useful. How did you get pulled into malaria work? That was a strange story too. Well, I was always interested in malaria and thought that maybe an immunochemical approach would help in the protozoan diseases. During the war, of course, malaria was a terrible problem, and they began to get cases up et Columbia. They asked me whether I thought that there was anything new that could be done for them, and I said that I would try to make a vaccine, if I could get enough parasitized blood. Whenever a pa­ tient was in sufficiently good condition, they would take about a pint of blood right after, or during a relapse. We tried to concentrate the para­ sites and make a vaccine. I applied for a grant from the OSRD, and they sent their malaria ex­ perts--three or four of them--to try to talk me out of working on human malaria. They said, "We have several monkey malarias and malarias in 151 birds. Why don't you work on something that is susceptible to experimen­ tal treatment?" I told them that there were patients in hospitals, that their number is increasing and that we can get human material. "That's all I'm inter­ ested in. I don't want to work on some other species' malaria. I'd like to try to get a better vaccine for human malaria." They couldn't argue me out of it. I said, "If you don't want to give me the money, I'll get it somewhere else." They finally came around and made a grant for the study. We used to send sterile centrifuge bottles with sterile citrate in them down to Cuba, to Puerto Rico where there were a good many cases. The people in some of the hospitals there cooperated with us, and when­ ever they got a red hot case of either falciparum, or vivax with terrific parasitemia they would send us two hundred and fifty cc. of blood. The Public Health people in Brownsville, Texas, where the planes always came through, were always alerted and were asked to put fresh ice into the thermos flasks which they usually did. We usually got these samples in very good condition and were able to concentrate the parasitized red cell stromata and make a vaccine out of it. We were rather discouraged at first. We didn't know exactly how to go about it experimentally, but I was talking the thing over once--I was invited up to Manfred Mayer•s--he had married a year or two before this, and hie wife was a very good pianist, and we used to play sonatas. I went up there end expected to have en evening of music. Manfred and I got talking about how discouraging it was to try to have a vaccine and not to know whether your patients were going to get malaria, or not. "If you had a healthy person, how would 152 you know whether he was going to get malaria, or not. He might not be exposed to it," and then all of a sudden his wife said, "Well, it's usually a month between relapses. Why don't you try to vaccinate them between re­ lapses?" Whether she was thinking of a Brahma Rhapsody, or a "relepeody", or whatever it was, she had the idea. We thought that was really something. Then we started doing just that. She--well, she gave us the idea. If possible, we would shoot the vaccine back into the same patient. Some­ times we got enough to vaccinate two or three patients with the same type of parasite. It began to look as if our relapse rate was less than nor­ mal that would be expected. Of course we didn't have any controls. We used every patient that we could get, and there weren't so very many. We got something like a twenty, or thirty percent reduction on fifteen pa­ tients. Well, maybe the Army would give ue a lot of their patients. I went down to the Surgeon General's Office in Washington and talked to the peo­ ple who were interested in malaria there, and they wouldn't touch it with a ten foot pole. They said, "You've got to show us first that it's any good before we'll give you a ward to work on." I went around the corner to the Bureau of Medicine of the Navy and talked to the people there--old Admiral Smith was there and Captain-­ well, I've forgotten his name, but it was somebody whom I had met in the ONR before. He locked ever our data and said, "Well, it looks as if you were able to do something this way. We've got ward after ward cf marines coming back from the Solomon Islands for whom we can't do anything, and maybe this would work. We'll give you a ward, a commander in charge, end you can work it out any way you want and see." 153 We started in with about a hundred patients an a ward. There was a Commander William A. Coates in charge, and we divided our patients into three groups. One group got the regular drug treatment, another group got normal human red cell envelopes, and the third group got our paraai­ tized vaccine which we made in the laboratory. They assigned• pharmacist mate to our laboratory to help in making the vaccine, and we would take-­ whenever there was a highly paraaitized patient in a relapse, Coates would get him to volunteer--he was usually very successful. He'd aay, "This mey cure you, and it may help your buddies, if there is enough there for them too." We'd get a pint sample of blood, a half pint of blood and make a vac­ cine from it. We would shoot as much of it as we could back into the same patient, and ell this was while the people who ware giving hemoglobin thought that if they had traces of cell- stromata, it would be toxic to the patients. We were shooting in a paste of stromata and not paying any attention to blood groups even. We didn't have any trouble whatao- ever. We kept very careful records on all the patients, the relapse rates and the clinical course of their disease. Just about the time that Coates was beginning to write up the results which didn't look particularly prom­ ising, he got e telegram to report on a ship. I called up the Bureau of Medicine and Surgery in Washington and got hold of Admiral Smith who had long since retired, but he was running the thing then--peraonnel problne and things like that. I told Admiral Smith what had happened and said that if we could have Coates for one more month, "he will be able to write up all the work, end we will really know whether we have anything or not." 154 The Admiral said, "Well, I don't know, but I'll see what I can do." Within two hours Coates had another telegram rescinding the first one. Some routine clerk had sent the first telegram out, and we finished up the study. It turned out that the relapse rate in all three groups was exactly the same to the nearest decimal. There was no influence with either the normal stromata, or vaccine. The reason we had used normal atromata waa that Manfred and I had found that we got a complement fixa­ tion with normal stromata in almost as many patients after a relapse as they did with the chicken malaria antigen that was routinely used as a diagnostic aid in the Army. We thought that if they were making anti­ bodies with their own stromata, maybe if you immunized them to their own stromata, it might affect the paraeitized red cells too. That was our second control, but they all had the same relapse rate. I don't know why it didn't work. It may be that we washed our para­ sites too much and washed any protective antigen away that they might have had on them, but anyhow it was the first properly controlled vaccina­ tion study in the history of malaria. It may be the only one there will ever be because it was discouraging, but at least it was properly controlled, and there were some interesting by-products. As I said, we found a complement fixation reaction to normal etro­ mata. There were three different complement fixation reactions going on and sometimes at the same time. Then also I had the idea that in malaria infections where usually the blood is only very slightly parasitized, I read somewhere that the mature parasites in malaria infection have hemin­ granules in them, and I thought that that ought to be detectable electro­ magnetically, whereas the oxidized hemoglobin and reduced hemoglobin with bivalent iron in the blood corpuscles would not be affected by a 155 OYL ',~'~ e magnet. We rigged~up--this was with D. Rittenberg's halp. He was a phys- ical chemist, and we fixed up a prow shaped magnet withe plastic cup around it, put it down in the cold room, and directed a fen against it to dissipate the heat. We took a sample of malaria infected blood where you had to search for a half hour to find the parasite, and we diluted the blood somewhat so that it wouldn't settle fest. We let it go all night in the powerful mftgnetic field of several thousand gauss, and the next morning there was a beautiful line of dark parasitized calls against the front of this prow shaped magnet. That could be aspirated .off. Just with the crudest technique we got a concentration of e hundred and fifty fold. I'm sure thet if W8 had worked it out more carefully, we could have concentrated it a thousand fold. That was one potentially useful he\$ --.- outcome also, but as far as I know, no one else hN- ever used it. They had acme success with suppressive dru9e--eome chemotherapeutic ae- preach. Yee--it was really mare success with prevention, 1 think, with sup­ pressive drugs then cure after the infection was once established. Chloro­ quine--if they took enough chloroquine they usually didn't get malaria, but it was very difficult under combat conditions to see that the men took enough chloroquine. The infection rate, in the Solomon Islands par­ ticularly, was terribly high, and there is a lot of drug resistant malar­ ia now coming from Viet Nam. Y•t• and even in eoma areas where we have been euccesaful previously es in BfaZil. Yes. Some day, I guess, there'll be a very good vaccine. There 156 were other people trying to make vaccines at the same time, and we wanted to join forces with them, but they wouldn't do it. We aleo tried to use the malaria vaccine--the vivax vaccine in schizophrenics who had been given shock treatment with malaria. Aleo eventually we tried to use the vivax vaccine in volunteers, a few prison volunteers, who allowed them­ selves to be bitten by mosquitoes carrying vivex. We had vaccinated them, but that vaccination didn't prevent the infection either. We never really found any antibodies other than the ones that were normally present to fix complement even after vaccination, so that there juet didn't seem to be a strong immunizing effect to the vaccine as we had it and made it. You say that gthera were in the field too. Theee were under the Officp of Scientific Research and Development, or the Navv 1 or whet? I think they had an OSRD contract too. It was Jules freund and a man named k. Jefferson Thomson. They were at the Public Health Research Institute et the time, and they had monkey malaria, cynomolgue, and were working on that. We thought maybe they would combine forces, and it would be leas wasteful, but they didn't like the way we made our vaccine, and maybe they were right because ours wasn't any good, but at leaat the Navy gave ua all the opportunities that were needed, end it was a very careful, thorough experiment. The patients were wonderful. It's a good deal to ask e sick man, "Give me a pint of blood?" Thay did it. Ygu worked in at least two areas then that were relevant to the war-­ that ia 1 the pneumonia pl:'Oblem and the maleria problem. Well, I had some secret jobs too during the war. They were very 157 much worried about ricin for one thing, and especially after there was a long article in the New York Timee on how the Japanese Army had asked everybody who had a garden to grow castor oil plants. Well, what they wanted the castor oil for was airplane engines, a lubricant for airplane engines, but we didn't know whether they were going to put ricin in these floating bombs that they had, send them over, and try to poison large areas, so my job was to try to immunize against ricin. The first thing was that we found that all the preparations of ricin were very impure, so before we could immunize againet it, we made it even worse than it was before, so that the whole question of offense and de­ fense--the two were really inseparable. That bothered me a good deal. The secrecy provision was foolish. There was another secret job on anthrax, and that showed the folly of trying to keep anything secret. I got Kendall, and I got Julianelle who was out at Washington University in St. Louis to help on anthrax be­ cause he was an excellent microbiologist. Penicillin had just come out, and everybody was trying penicillin on everything, so Julianelle tried penicillin on anthrax infected mice, and it cured them. This was a tre­ mendously exciting discovery. Well, he wasn't allowed to say anything about it because it was a secret project. The only thing was a top se­ cret report. Well, six weeks later the newspapers had it ell from the Mayo Clinic because they didn't have a government contract. There was no secret about it. They could publish it which they did immediately in the newspapers--sensational cure of this dreaded disease anthrax. Well, Julianelle was just knocked flat by that because it was the biggest thing he had done up to that time, and he lost it. It was reelly terrible. 15B The whole question of secrecy over ricin wee stupid too because some General in the Chemical Warfare Service who hed drunk too many cock­ tails spilled the whole beans that there was a project on ricin end other highly active toxicants going on. Then all of a sudden the classifica­ tion was removed, end we were allowed to publish. There were three lab­ oretoriee working on our study. Northrop had gone out to California. Dr. M. Kunitz was still in New York. He had worked with Northrop, and They had he was at the Rockefeller Institute. crystallized ricin. CJiLr prL·<lccc ~--·. We hadn't. I telephoned them both. ·,;,--....... --t <!rjs' '- It was purified., but not i.:r~·•!heJ l"a 1/ihc .......... ~ - ~ p,,;duet. I seid, "I'm going to write up what we've got and whet we're allowed to publish." We weren't allowed to publish on the biological side, but we were allowed to publish on the chemical side because this General had already spilled the beans. I said, "I'm going to publish end send in my paper. Will you do the same, and we'll all publish in the same number of the same journal." You had to send an article info Washington to get clearence ~ i t , even though it was nonclassified, because the article was under one of these original1.y classified contracts. They said, "Yes, they would." rt -Y-' I wrote up--Elvin Kabat had been helping me on this study. Actually /l we had a gas chamber in one of the lalx>ratories up at P & S where we were insufflating the ricin to animals end studying the antigenic, the antibody response after insufflation. That part we were not allowed to publish, but we had a lot cf chemical work which we did publish. I eent the papa:,: in and got clearance, end before Kunitz and Northrop could send in their papers, classification was clamped on again for some unknown, stupid reason. I mean it was all public property by that time. I was 159 allowed to publish in a footnote that Northrop and Kunitz had crystal­ lized ricin, whereas they were not allowed to say anything about it. I published the paper, and the first knowledge that ricin had ever been crystallized was in a footnote in our paper that they had done it. It wasn't until years later that their papers came out. I still have a lot of classified stuff here. I don't know what to do with it. The orders were originally that it wasn't even to be burned-­ the classified laboratory notes. I suppose the best thing that I could do would be to burn it. Send it ba£k to them. There's a lot of biological stuff that has never been published. Were vou associated withe team in this study? Yes. Well, there were these other people working on it--Dr. A.H. Corwin down in Baltimore at Johns Hopkins was working on it originally, but he hadn't been able to take it very far. We did most of the immuno­ logical work up at P & S. The work that Northrop and Kunitz did was purely chemical. We were the only ones working on the immunological side. Yoy mentioned biological information. Well, that was it--the immunological side has never been published. I think the only thing we published was that even if you made a toxoid by the standard formaldehyde methods and reduced the toxicity a thousand fold, it was still such a nasty substance that you got necrosis and ulcer­ ation. There was lets of trouble over it all the time. We were never 160 able to get a harmless immunizing fraction from it. You had to be awfully careful. We wore gas masks whenever we handled the dry powder. The Army supplied us with those. What sort of intereats--the Armv had financial inter~st. Well, Elvin Kabat actually·went out to the Dugway Proving Grounds several times. He was there when they fired canisters containing this stuff to see how far it would spread, and whether it wes a practical way of poisoning animals or people. It wasn't very practical. The Army lost interest in ricin anyhow because it turned out that the botulinum toxins were perhaps even a hundred times, or a thousand times worse than ricin which is one of the worst things imaginable. They decided that if they ever used ·anything of that sort, it would probably be a botulinum toxin and not ricin. The Army--well, the Air Force got a terrible scare. The whole country, the Army people who were in charge of the Chemical Warfare Service got a terrible scare when the news item was published in the Times that every Japanese family had been asked to grow castor beans. Not only that. but didn't some of their paper beloons •••• Yes, they were supposed to have contained bacteria. I don't know whether they did or not. I don't know either. Incidentally. some of the studies on the drift of air--the drop• of ex­ ploded canisters in the Dugway Proving Ground. the wav that atudy wea handled ~n the senee of drift. the area covered. ia some study. 161 Yes--there were very thorough studies made. Was the experience with OSRD a pleasant one? A what? A pleasant one? Yes--one always met interesting colleagues in Washington. It was a bit hectic sometimes to take the six-thirty train down to Washington with drawn shades so that no bomber could see that the train was illumi- nated. Thoee wefe long trains, and those were old care too. Yes. Well, the cars are still the same, I think, because if you travel by train between New York and Washington it's almost impossible to find a car, pullman or coach, that hasn't got flat wheels. They never seem to change them. They got lion service out of those care during the war years--I know that. How did you feel about the government directed research in this wartime period? Well, it was all right, except the classified research. I made up my mind as a result of my experience with classified research that I would never allow myself to be drawn into it again. It was not only the comprehensive clearance procedures which took vest amounts of time, which one could understand, but it was the stupid restrictions, If the restric­ tions had applied to the whole country, there might have been acme sense in it, Take this Julianelle episode--the people who didn't have govern- 162 ment contracts were under no restrictions whataoever, so that it wee grossly unfair to the people who were in it. They found the same thing during the nuclear energy work; that the lack of contact and the lack of freedom to discuse hampered the work very seriously. General Groves was a nasty word, a four letter word in science at that time. Hp had hip p;oblems ,. he underp;t90d the- Yes. As an administrator I don't suppose he did too badly, but cer­ tainly the scientific aspects of the nuclear development were hampered a greet deal by secrecy and a leek of contact between people. At least in Washington, at the meetings of the central board, the group.that was put­ ting up the funds, you could discuss things freely, end that helped some. They usually got most of the people on a project together, and they could talk to each other even if you couldn't eay anything to your wife. Let me turn this over. You'd had at p & s the special Harkness Fund that had sustained your scientific research. Prior to that at Mt. Sinai• scientific research had never really gotten oriented, or--the demands were greeter than the time and energy vou had, or at least that's the way it appeared. and scientific research was going tp euffer unless something was done. Befo;e that at the Rockefellp£ Inptitute they had enjoyed op­ portunity and funds apparently sufficient for their pur90ses. Hgw did vou look upon the buxgeoning p01twar ye1ra 1nd the drive to astablieh the National §cianc, fgundpt:aoen? Well, long before that the Harkness Research Fund wee insufficient to pay the expeneee of a postdoctorate co-worker, a laboratory helper, the expenses of the research, the animal care, end all that, so that I 163 applied to the Rockefeller Foundation, and they supplemented the Harkness Research rund for nine years after the war, and when I left and went down to Rutgers, it was the National Science Foundation that carried on. Since then, I've done all of my work under the National Science foundation, al­ though Rutgers supplied my salary. The grant did not pay my salary at any time. That came out of the Harkness Research fund, and Rutgers paid my salary when I was down there. Since the war there has betn this deep interest in medicfl affairs. medi­ cal needs. thp desire to broaden what is called the scientific beae-NIH in particylar. byt this is not limited to NIH. There's gfeat basic wo;k being supported by the National Science Foundation, ONR and Bo o...ri.. I had a grant for a time from the ONR also. I was also on one of their review boards. I also had a grant f~om the Office of the Surgeon General for a few years too, to supplement the Harkness Research Fund and I guess for a year or two down at Rutgers also. There's been some criti­ cism, I guess, of people on these boards giving grants to themselves, but we always withdrew while the other members of the board were consi­ dering whether we \>Jere to get our grant, or not. Most of my work since the Columbia period has been subsidized by the National Science Founda­ tion. They've been wonderful people to deal with. They require a mini­ mum of red tape and reports. Whenever it reaches the amount that it hae, somebody is going to take an extra look at it and second-guess a bit. Yes, of course. That has to be expected. I think perhaps we've gotten--well. the basis 164 for scientific research has been extended WIY bewnd what waa ever dreamed of certa¼nlv bv the Second World War. Yes. The great difficulty is that the expense is increasing all the time, Each year the expense of research rises more than the increase that has been given by Congress, or at least this has been so during the last couple of years. Now that the funds are relatively stationary, costs have spiralled even more, ao that you have less than you had before. Even if you had the same amount, you have relatively less, but I don't know what we can do about that. The main thing, I think, is to get rid of this Viet Nam war end the crazy expenses that it ia entailing. Are vou atill functioning on the chemistry of the imrnune 1eaction? Yes. We ought to take a look ahead. You might went to say something about the qver•ll etmosphete •t Rutqe~s and h•t• at New York University, and perhaps this before we take a look 9head in the field. Well, I told you, I think, how I went down to Rutgers with my staff without any delay. It was through Dr. Waksman who--well, another one of my postdoctorate people was Byron Waksman, Dr. Waksman's son, who was with me for a year. I guess Dr. Waksman heard more about the work that was being done in my laboratory from his son. When Dr. Waksman put so much of the royalties from streptomycin into the Institute of Microbiol­ ogy, he asked me to come down there and start an immunochemical group. I couldn't leave right away, but I went down and conducted seminars fairly regularly the first year, or two that the Institute was function­ ing, but finally he was very insistent about it. He had laboratory 165 space and had it all worked out. I asked Columbia to let me go a year before I would have had to retire. As I said, Columbia was extremely generous and gave me a year's terminal leave. That was the way it started down there at Rutgers, at the Institute for Microbiology. When I was looking around at the laboratories that had been assigned to me before I went down, it turned out that there was no hood in them. An organic chemist can't function without e hood, with draft and suction. Dr. Waksman was really wonderful about that. His laboratory was the only one that had e hood built in, and he said, "Well, I'll take some other laboratories, and you can have mine." I thought that was moat unusual for the director of an institute. That turned out not to be necessary because the Executive Secretary, Edward R. Isaacs was a very ingenious fellow. He figured a way of running ducts into the laboratories that had been assigned to me so that a hood could be built in there. That's what was actually done, and I had all the facilities I needed. I had my grant from the National Science founda­ tion and wonderful associates to work with--the other people there were -/ Werner Braun, Vincent Groupfes, Vernon Bryson, Henry J. Vogel finally, '-- W. J. Nickereon--they were very stimulating people. We used to bring sandwiches for lunch, meet up on the top floor, and have lunch together very often, and there were some stimulating discussions too. The younger people came, but they never had a real lunch room so that there was not too much contact with the rest of the staff. I missed a real lunch room a great deal, but one made good friends there, and I still keep contact with them. Were you free tp develop within your gwn laboratory as vou pleesed? 166 Oh, yes, anything I wanted to do. I thought originally that I'd only be going down there for two or three years, until Dr. Otto J. Plescia was fully launched, and then I would pull out, but it was euch a congenial place to work that I rented an apartment--! did that right in the begin­ ning--rented an apartment down there and fixed it so that although I was there every day, except Saturday and Sunday, I only had to make three round trips a week between New York and New Brunswick. Of course I thought it was only temporary, so I didn't give up my apartment in New York. Then when I married again, my wife agreed to come dawn ta New Brunswick whenever it was convenient for her, whenever aha didn't have rehearsals, or lessons to give. We managed with two domiciles for nine years. Eventually it was the New York Subway that made me give it up. Dr. Plescia is a very fine person, and he had complete freedom to develop along his own lines. Although he took an office on a different floor that wasn't convenient, he never showed any signs of irritation, or jealousy at my staying onJ in fact, he always urged me to stay on whenever I would talk to him about it, I never felt that I was in the way. He went off on hie own tack mostly, although we did a good deal cf work together all the time, We were both extremely happy down there. When the new Director came in, when Dr. Waksman retired, there waa a little friction with the staff because the staff wanted one of the peo­ ple who was there in the Institute ta be the new Director. Dr. Waksman had his own ideas, end he proposed someone else, or he imposed someone else. Of course, that irritated the people there. Dr. Waksman naturally thought that the Institute was his baby since he had gotten the people together and had organized the Institute. When he chose the new Director ·-~ Dr·. :s;-_""'rJh. everybody was very unhappy. Je.e. a. Lampen, the new Director, faced a 167 rather delicate situation when he took over, but he handled it with such tact and proved to be so congenial and able, a real scientist in his own right, that everybody liked him very much from the very beginning and re­ cognized that Dr. Waksman hadn't made a bad choice after all. Joe is still director there and a very popular director, gets along beautifully with the staff and has his own laboratories and carries on very signifi­ cant research. He is Dean of the Inatitute of Microbiology. It's a separate faculty. The whole Institute has worked out very happily and very well, and I regretted very much quitting, but ea I say it was the New York Subway that made me mies eo many traina in the morning. I'd never know whether I would have to run for the train, or whether I would mis ■ it, or whether I definitely miesed it. If I did miaa the train the whale morning would be lost before the next train got to New Brunswick. It just got too nerve racking. My friends here at New Yark University, Baruj Benacerraf, Chandler A. Stetson, and Zaltan Ovary, when they heard thet I was coming beck to New Yark, ...,.were in the fortunate position in the Department of Path- . W£&an l elegy of having a couple ~f~atariea. People had moved from this floor into the University Hospital, and they said, "Here are a couple af laboratories. If you want to go on working, they're yours." 1 had nine thousand dollars left over from my grant at Rutgers from the National Science Foundation, and they vary kindly said, "You can tranef ■r it to New Yark University.n Then they renewed my grant for three years and then for another period af two years. I'm now faced with the question whether to eek fer another renewal or not. I think I will take Dr. Kabat•s advice end talk 168 t h a t o v e r w i t h Mrs. E n g e l who is t h e a s s i s t a n t program d i r e c t o r . I d o n ' t want t o be i n t h e p o s i t i o n o f a c c e p t i n g a g r n n t t h a t m i g h t gn t o some y o u n g e r pereion a n d m i g h t i n t e r f e r e w i t h B career i f h e d o e s n ' t g e t it, We s h a l l see. I have enough a n t i s e r a and materials t o go o n work- i n g w i t h o u t any g r a n t . New York U n i v e r s i t y h a s p r o m i s e d me t e c h n i c a l help. I c a n manage w i t h o u t B g r a n t if t h e caituation is w c h t h a t I d o n ' t need one, or 1 won't g e t o n e w i t h o u t d s p r l v i n g someone elcer o f i t , Well. what l i e s ahead i n t h e cornPlement f i e l d ? Ax8 vou w o r k i n a i n t h a t field now? No, I h a v e withdrawn from t h a t f i e l d . It's g o t t e n e x t r e m e l y c o m p l i - c a t e d 3nd complex. Manfred PI, Mayer who worked w i t h m e o r i g i n a l l y o n com- p l e m e n t h a s gone on t o B pXOf@88DrShip 89% J o h n s Hopkins a n d t o d a y is o n e of t h e two l e a d i n g a u t h o r i t i e s , I g u e s s , i n t h e w o r l d o n complement. He and Hans J, M h l e r - E b e r h a r d a m c o m p e t e n t t o f i g h t i t o u t and work i t o u t c o m p l e t e l y e v e n t u a l l y , b u t i t ' s a whole complsx series o f e n z y m a t i c reac- tions. Wet s t a r t o d t h e modern d e v e l o p m s n t i n complement by ehowing t h a t it r e a l l y was 8 eub8tencer, or a c o l l e c t i o n o f 8 u b s t a n c 8 8 . I want t o s e y s o m e t h i n g a b o u t t h a t diagram--1 d o n ' t know w h e t h e r you saw t h e d i a g r a m e x p l a i n i n g t h e f o u r componants of camplement. Well, o f c o u r s e , now t h e y knaw t h a t t h e r e a r e a t l e a s t n i n e components. At t h a t time t h e r e was e v i d e n c e t h a t t h w e were f o u r , a n d I t h o u g h t t h a t it would b e v e r y u s e f u l i f o n e c o u l d w o r k o u t a d i a g r a m showing t h e r e l a - t i o n a h i p s between t h e f o u r components of complement-which combination8 gave h e m o l y s i s and which d i d n ' t . I t a l k e d t h e t h i n g o v e r w i t h Yale Kneeland, F r a n k l i n M. Hanger, and Aobest Laeb up a t P & 5 . Every time I made a model d i e g r a m , t h e y would p i t c h i n and c r i t i c i z e i t and m a k e 169 suggestions. The d i a g r a m which f i n a l l y e v o l v e d was a r e s u l t o f t h i s whole Department o f M e d i c i n e w o r k i n g a n it. T h a t wae v e r y s a t i s f a c t o r y a n d v e r y pleasant, But you've s o r t o f withdrawn from t h e comolement arm. Yes, I h a v e n ' t dona a n y w o r k a n i t s i n c e t h e first two ox t h r e e y e a r s a t Rutgsrs. We had a c o u p l e o f 9 ellows t h e r e who j o i n e d u s i n t h e complement work, F- rtaEaTor - EI v e r y b r i e f time a l o t o f p r e s s u r e was b r o u g h t t o b a s r t o h a v e me work on the mouse m i l k f a c t o r up e t Columbia, a s t u d y which w a s n ' t going t o o w e l l . I f i n a l l y d m i d e d t h a t I would do some work on i t , and t h a t r e s u l t e d i n v e r y p l e a s a n t c o o p e r a t i o n between Cushmen D. Haagensen who was i n c h a r g e a f t h e mouse c o l o n y t h e r e and some of t h e o t h e r p e o p l e d o v e r e t t h e Dsl'iJPield Hospitel, I did e l i t t l e work, b u t d i d n ' t m a k e too much p r o g r e s s o n t h e mouse m i l k factor. P f e s c i a h a s gone on w i t h t h a t work. I was n o t a n x i o u s t o g e t i n v o l v e d i n t h e canctPr f i e l d b e c a u s e my s o n had a l r e a d y made, a r e p u t a t i o n for h i m s e l f a8 a r e s e a r c h worker i n cancer. I felt t h a t o n e H a i d e l b e r g e x fn a field wa8 enough, so I with- drew f r o m t h e mouse m i l k f a c t o r w o r k a8 s o o n ae I c o u l d p o s s i b l y g e t o u t of i t , You're s t i l l deeD1.v i n v o l v a d i n t h e a n t i c e n a c t i b o d v r e l a t i o n s h i p . Yes, m o s t l y i n r e l e t i o n s between c h e m i c a l c o n s t i t u t i o n and immunolo- giccsl s p e c i f i c i t y , I t ' s so much e i m p l e r t o work i n t h e c a r b o h y d r e t a f i e l d because t h e c h e m i s t r y o f c a r b o h y d r a t e s is 80 much further advanced t h a n t h e c h e m i s t r y of t h e p r o t e i n s u r f a c e r l e t ' s s a y , which p e o p l e knew awfully l i t t l e a b o u t . I ' v e bean d o i n g most o f my work un p u l y a s c c h s r i d s s , Y 170 but when I started working here at New York University I made up my mind that I would try to apply some of the ideas I have on the nature of an immunologically reactive grouping on a protein surface and see whether there ie any hope for an approach along the lines that I had thought feasible. It's a kind of hit-or-miss approach. I have been working on a number of immune systems wherever possible and using the microcomple­ ment fixation technique of Lawrence Levine. I went up there, watched him work at it, and then adapted his technique into a still more micro method for the kind of thing I wanted to do. I have done some twenty-five ex­ periments on different protein antiprotein systems to try to see if I can localize the immunologically reactive grouping. It was e forgone conclusion that most of the experiments would turn out negatively, and for that reason it's the kind of a thing that I have to do myself. I just can't entrust it to any younger person because it would be too discouraging. Whenever I'm not too busy on carbohydrate reactions that yield really important information and are very exciting, I go back to the proteins and work on those. This last year there has been so much tuming up all the time in the carbohydrate field that I haven't done any work at all on the proteins, except to carry forward some work that was started a number of years ago with one of my graduate students who never finished. He was going to write up a possible dissertation, but he never wrote it up. rinally he sent me his notes, and I have been going back over some of his old prepa­ rations, and we have immunized some rabbits with them. I have tried to ,a. £.:. hi~ V'n ;t!.:&I ~ ' - - · y - - -.._,., put i n ~ number o~groupe that would be more or less on the protein surface and make them larger and larger ao that they would stick out more and more. The idea was eventually to see where it would begin to influ- 171 ence immunological specificity, but there too so far the results have been negative using hie old materials. Whether it will be worthwhile trying to make some new preparations or not--1 have some crucial experi­ ments that are underway now that will tell. Some of the early ■ nd sirople gene1pli19tiona in the field are related not only to work that YOH did )(9Uraelf. but work with others. Which generalizations do you mean? l'm thinking of the th19rv with ,,,,ranee to this whole DJ.OCess that takes place, There have been g~her and more complicated. more complex theories edvenced--Linus Pauling and others. Yes, well, Pauling--! was very much amused really when Pauling and Campbell published their attack on our precipitin theory because they ended up with exactly the same kind of equation. They eaid that our as­ sumptions were unnecessary and arbitrary, but when they eubstituted their own assumptions, which Kendall and I didn't like nearly as well as our own, they came out with the same equation anyhow, so it didn't really matter very much. I think I've always said that an equation with two constants can solve almost any problem. Mathemeticians taught me that when I was at school, and therefore that our equation works is not sur­ prising. You can me~e any kind of assumptions that you want, and if you put in two constants, you get an equation that will fit a curve fairly well. It just so heppena that the constants that we chose had definite immunological meanings. They didn't seem unreasonable to us, and they still are constants, I think, that the immunologiat finds useful. You ■ till see our equation in other papers every once in a while-- 172 people who are interested enough in thet part of immunology. It has even bee~ applied in virology. Yowr own theory P¼loweg VDU 59 pred¼ct and your prediction, •••• Yes, predict a lot of these cross reactions that I have been working on. The fact that cross reactions do occur hae often been used in the opposite sense, to tell the organic chemist what he is going to find when he gets his chemical work far enough along. That's been extremely useful in many cases. Actually up in Ottawa now in Adame Polyeaccharide Research Laboratory it's useful. I gave o lecture up there and did same work on one of their polysaccharides. I wee able to tell them something about three of the four sugars in the polyeeccharide, end as a result of this they have a small library of antieera now and they're using them as pre­ liminary test objects for getting some idea of where thay are. The work is useful completely outeide of immunolog~•, or biology too. This PIQ!i?r that I .read, or some handwrit3en n9tee that I read just the other day where immunochemistry has been picked up bv pathologists. Yes--immunopathology now. There's an immunogenetics, and there's LI even a Max Planck Institut1 fn "" Immun#biologie in Germany. \_., Well, the utility of the immur.ochemical approach ie expandi~g ell the time. What do you aee up ahead in the antigen antibad¥ teaction? Well, I think the most important thing to be done now is to try to find cut what the reactive grouping on antibody looks like and what the reactive groupings on antigenic proteins look like. We have a fair idea new of what they are on polyseccharidee. Any polyseccheride can b• anti- 173 genie if you have the right antibody. The question is how to find the right antibody. We have no idea whet makes an antigenic grouping on proteins, and that 1 think is the moat important problem directly ahead. The biochem­ ists are trying to work it out an antibody by studying the order of the amino acids, the arrangement of the amino acids and how the various chains are put together, but if every antibody is a little different from every other antibody, it's going to be very difficult to find out which amino acid in the enormoualy long chains ia responsible for just the final twist that makes en antibody grouping a particular antibody grouping. That'e something that eventually will have to be done. th.Ott;. 1 still think that my hit-o.r-rnisa way of going about tkW.:iurface groupings on proteins is e possibly useful ons, and if 1 have a few more years yet to work, I'm going ahead along those lines. Do voy see anv need for new tools. new eguiement? I think that equipment haa gotten ao expensive and so sophisticated that we have about everything we need--what with the gas chromatagraph and the microamino acid analyzer. I think perhaps there will be refine­ ments of x-ray technique. Just whether refinement will come through mathematical analysis, or through refinements in apparatus that change the wave length, or a different application of computers--1 have no idea, but I think one of the big hopes in understanding the relation between the chemistry of proteins end their immunological behavior will be the development of the x-ray techniques. At least now they are able to tell how the amino acids are folded and what kind of troughs there are in pro­ tein eurfaces, the irregularities of shape. That's a beginning toward 174 en understanding cf what the protein surface is like. They've made more progress en enzymes because they can stick a small molecule in there and find changes in shape and changes in reactivity, but they'll probably ex­ tend that precess to antibodies and antigens too. Do you see an increased need for a kind of quantum mechanical oriente- - tion? Do you mean new mechanical apparatus? Thinking. Well, I think new ideas are always vital. That's what makes progress. It is the new experiment that yields an unexpected result. The interpre­ tation of the unexpected result is the thing that gives you e chance to jump forward. That's why I was so terribly happy about this galactan work, the yeast galactan work that I did with Morey E. Slodki out in Peoria, Illinois. It did everything that was expected, and then the unexpected things were so beautiful and gave us such valuable information that the unexpected turned out vastly more interesting than the expected. When I wrote to him and asked him to send me some cf his material, I just thought, "Well, I know which sera this is going to react with. I'm sure of it." It did everything that it wee expected to do, and then these terrifi­ cally unexpected things turned up and told us something about the struc­ ture of Type XVIII pneumococcal polyaaccharide that we didn't know before, told Slodki what grouping in his galactan the acetyl group is on, and then with the Salmonella per9tvphi A we learned something about the importance of the galactose residues. Residues were in one or more of the three Kaufman antigens which nobody knew anything at all about except in so ~ 175 far as they are end groups. Well, the next two residues now must be galactose, and we know how they are linked. • I have some material here now from one of Dr. Edsall's co-workers, Geoffrey Edsall's co-worker who has separated antigen 12 from the other two and it's from typhoid anti­ sere and not from paratyphoid A serum, and if I get a reaction with it, it's going to be interesting. If I don't get a reaction with it, it J_, isn't going to tell anything, except that the ea-called Kdufman antigens .I\ are not exact entities. They differ in the different organisms in which they occur. We'll learn something from that too, I think. Is the effort still on to purifv some of the sugars? The pneumococcal polysaccharides are still of great chemical inter­ est because we know the fine structures of relatively few of them, and each one is so different from the othera that it's a fascinating study just to take a whole series and one group of microorganisms and find out all the many things that a single microorganism can do to change immuno­ logical specificity within the group. I think that study will probably continue at a slow pace.· J. Beddiley is working on it in Newcastle. I just had a latter from Dr. c. V. N. Rao who worked with me on the Type IX pneumococcal polyaeccheride--he would like me to send him some Type IV to work on now. We know very little about the Type IV. I have to de­ cide w~othar I want to go ahead working on that, or whether I'll send it to him. You-let's take four areas. had a chance to survey interests, tech- You niguaa, people in Japen. in India--voy had some students from India. You've had students f:t9m South America. 176 Yes, and some Germen co-workers. South America, Central America, Mexico--a very premising young man from Mexico. The immunochemical approach ;n India. and Mexico. I know, fer exam- Jsppn ple. that you agt some elephant sere. something ygu always wanted when vou went to India. but the approach that they have. 3he problema they con- front are different as is the context in which they must function and operate and work. Well, of course the problems are different in each country but I think the methods with which they approach the problems are more or less the sam.e. We have a definite set of principles governing a science, end we can't do tao much violence to them. The Japanese have been extremely apt, I think. I think they've gone ahead faster along immunological lines than the Indians have. They've had more facilities put at their disposal. When I went over to Japan it was, in part, to find out why the Japan­ ese were not paying royalties into the Waksman roundation. They were mak­ ing streptomycin and not paying royalties into the roundation. Dr. Waks­ man had a lawyer representing him. The roundatian people were not doing very much about it, and the lawyer waen•t getting very far. The only thing he succeeded in doing was to block the attempt cf Japanese pharma­ ceutical houses to have the Japanese version of the contract declared the bfficial version. That would have been fatal because no two Japanese ever agree on what any written thing in Japanese means, so that that would have spoiled the whole thing. I got in touch with four leading pharmaceutical firms and asked them to send representatives to see me and talk over the matter. They had 177 claimed that the government had forbidden them to furnish royalties, and that didn't seem to be actually the case. These people refused to come to see me until the night before I left Japan, and then they barged in during a dinner. The last evening I was there we were going to have some music. I interviewed these representative ■• They waran•t the laaet bit interested in research. Dr. Waksman didn't want the royalties for his own use. He wanted them to go into thie foundation which was to make grants to support research mainly in Japan and to exchange acientiate be­ tween Japan and the United Stataa both waya. Thay weren't the least bit interested in that. They claimed that they weren't making any money, but at Internation­ al House I had been told about some cf the Japanese financial methods, and the way they don't make any money is that the people who lend them industrial loans, the big benkera, siphon off all the profits, and there usually is nothing left for the common .stock holders ■o they don't make any money. I said to these fellows. "Do you have a car1" "Yes." I put that question to each one of them, and each one of them had his own car. I said, "Most of my professor friends who are acting es your consultants and who are on tha Waksman foundation don't have cars." They were making money at least personaliy. Their attitude was really dreadful. I wasn't able to do anything with them, but eventually it was straightened out, and some royalties want into the Wakeman founda­ tion at a greatly reduced rate. All I told them was thet if we could put them in jail, we ce~teinly would do it. Jhe Japanese trip wap come,ned with the meptinq in Bangkok. 178 Yes--well, the real reason I went over tc Japan was that I wanted to go to the first Asian meeting of the World rederation of the United Nations Associations, and in order to pay for the trip I agreed to give e series of lectures throughout Japan. The Rockefeller foundation gave me a thousand dollars toward my e~penses for giving the lectures in Japan. I arranged for the lectures on the way out and went on to Bangkok and then went back to Japan after the meeting in Bangkok. That was a very stimulating and enlightening experience because Mrs. Roosevelt was a member of our delegation, and it was a marvelous privilege to h~rk with her. I had a project for a new kind of peace con­ ference that the American Association for the United Nations was going to back, and as I conceived of it, it was a completely impractical thing. Mrs. Roosevelt immediately put her finger on the good points and on the politically impossible things that I had suggested, and with her help it was made into something which really would have been useful, I think, if it had passed. There was too much opposition to it. I missed going to Angkor with Mrs. Roosevelt and about half of the people at the meeting because the day they went to Angkor was the day that my resolution came up in the plenary session, and I had to stay there and fight for it. It was very nice also giving a lecture at the Chulalongkorn Hospital in Bangkok. One of Manfred Mayer's Ph.D. students--! don't know whether she got he= Ph.D. with him or not, but she was there fore year or two taking his courses and then went back as bacteriologist to this hospital in Bangkok. She came to my lecture and asked afterward if there was any­ thing she could do for me, and I said, "Yes. I have one more morning in Bangkok, and I'd like to do some shopping." She said, "Oh, my sister has a car, and we'd like very much to take 179 you around." They did, and so I invited them to lunch before I went out to the airport. When I thanked her, she said, "Well, I would do anything for the teacher of my teacher.• I thought that was going a little further back than most Americans would go. I had one disappointment in Bangkok. I thought I might be playing a V.J-i /::-, k_,\ C ~ sonatas with the King, but he wean' t tbere et I hw tJ.1111:9. He was there, but the man who could have arranged it who was one of the deans of the medical school, wasn't there, so nothing came of it. I had a lot of music in J .. pan. Professor Tomio Ogata was my sponsor there, and he knew a lot of musicians. What was the inte;est in the elephant in India? Well, I just figured out that with an animal like that native to India they could get large quantities of any antiserum that was needed relatively simply, and Avery always used to say when we were running low on serum, "If' we only had an elephant!" That's what gave me the idea, and when I was invited to go to India I thought, "Well, this is the chance now to see whether the elephant is a good antibody former, or not." Apparently there were no data, nothing in the literature. It was really very hard to find an elephant, but finally the Maharajah of Mysore came across with one of his special elephants that had been working in the movies, and he was willing to risk that elephant which I thought was a very fine thing on his part, We never did get a second bleeding out of that one. We immuni~ed him, but we never found out what had happened lBO but one of the work elephants gave ua very good antibody considering that 11U0 ..-·-y------ we only gave him one injection. Wanknow that elephants can make anti- bodies. The Office of Naval Research, or the Bureau of Medicine of the Navy had some relatively pure human gamma globulin that they were distributing around to various navy poate, and they gave me a whole pound, a plastic bag of human gamma globulin, and l took that over with me as an antigen because I thought that if they had an antigamma globulin serum, they could :-Jc:.-..-· _F_l (' tu$ check ~antibodies, things like that. It would probably be the moat useful thing to start with. I finally took a trip out into the jungle from Mysore. It was about eighty miles to where the Maharajah had his work elephants. These huge beasts came in from work in the jungle, and they wouldn't let us touch them until they had had their bath. There was a big river there, and they drove these elephants down into the river. The chief forest ranger who was arranging all this waited until the elephanta had roiled up a whole lat of mud end sand at the river bank, and he scooped 1.p a handful of it and started brushing his teeth with this gritty mess with his index finger. I thought that was wonderful. Well, when the elephants came out, the mahout of the biggest one got him to lie down. They had sent a pediatrician from the medical echool to do the actual injection, and we figured out that we'd like to give it behind the ear because they said that was the thinnest part of the ele­ phant's skin, We'd give a subcutaneous injection there, and then at the same time an intravenoua one into the ear vein which standa out in the ear like a tree trunk. The minute the elephant felt the prick of the 181 needle he got up and scattered everybody. Well, finally the mahout by talking to him continusouly persuaded him to take the two injections. Then the young pediatrician went back a few weeka later, and they would only allow him to take five cc. of blood. My goodness. The mahouts were afraid we were going to kill the elephants, and then they'd be out of a job. Well, this huge beeat--they bleed ten liters if he gets rambunctious just to calm him down. They wouldn't let him take more than fiva cc., but that was enough for analyeis. We got a good anti­ body rea~onse, so we knew the thing worked but nobody ever followed it up because the mahouts made such a strenuous objection. Then when I got to--l haven't thought about the Indian trip for so long--the Central Drug Research Laboratory, they aant a man out to get some elephant serum. 1 wanted to see if elephant complement was any good, end it turned out not to be any good. It's relatively inactive, but this poor fellow had to go a hundred and twenty-five miles in one day--his round trip was a hun­ dred and twenty-five miles mostly over a very dusty road. He came back absolutely covered with dust, but he had about ten cc. of elephant blood. We got the serum from th~t and tested it. This was in Lucknow which is a b. ;,__ -~"/', v.-d~v;;, most interesting place. That' a where my former co-worker 511:i. 'iine we; assistant director of the Central Drug Research Institute. We worked there with the elephant complement and found that it wasn't useful. But I was very much heartened by the number of really dedicated people that I found in India who were trying to make things better, and I suppose they are still doing the &ame thing but under terrible odds. Moat of the young people who come aver here to work and study find it very difficult 182 to get jobs when they go back which is verry strange because they need a vast number of competent people. That's one of the difficulties. Appar­ ently there is a good deal of politics and political favoritism in assign­ ing jobs. You would think that with the problems they confront they would utili;e these trained people 1 but that doesn't seem to be so. Well, they think that if they train somebody, he knows enough for India, I guess. That used to be the trouble too, in the early days at the Rockefeller Institute. They would have people come over for a few yeare from Europe, and then when they went back and competed for a pro­ fessorship, as they all had to do, they always held competitions--they were discriminated against because they were going to introduce foreign ideas, and the established order didn't like the introduction of foreign ideas. They had some pretty severe fights on that account. Vested interest of one kind or anothe5 is of the order of life. Yes. Well, that's responsible for a lot of difficulty in the uni­ versities now too. Yes. I noticed in the correspondence which I read that while some of your colleagues, co-workers and friends in the field differ, you never lost the sense of oneness that you were all involved in this great ex­ citement. It's necessary I think to have differences of opinion and interpre­ tation for any science to progress. As long as people don't put it on a personal basis, there's no reason why one can't discuss things like that 183 openly and try to get to some mutual agreement, and it isn't so terribly important, if one doesn't get to a mutual agreement either because in the end whichever view is correct usually triumphs anyhow. I mean most of the people objected to the idea that antibodies were multivalent. They came around in the end anyhcw--they had to. All the data pointed in that direction. I remember one lecture that Pauling gave in Brocklyn in which he insisted that antibodies couldn't have more than two reactive groups and yet on this diagram in order to get a compact aggregate he had to have one that had three groups. I pointed that out after the lecture. He took it very properly. I have the feeling alsg f:rqm the correspondence that it shows that gne of the problems wa5 di.:r:ect 'face to face communication, that if ;you 50uld sit down and talk with I man •••• Yes. Well, very often if a discussion got at all heated in a meet­ ing, I would break it off sometimes and juet sit down end write a letter efterwardo and try to work it out privately with a person because you can say things in a letter that you don't like to have everybody in a large room hear. I think in the beginning a lot of people resented having im­ munology put on a 1110re chemical basis and especially on a quantitative basis because there used to be lots of papers on quantitative methods, and they were all just end point titrations, and I always insisted from .-fkJr the beginning that whenever they were talking about•·l<ind of quantita- tive method Jllla;;:-they were talking about something that es yet hadn't been measured. 184 INDEX Acetic acid 41 Acetyl amines 62 Adams Polysaccharide Research Laboratory 172 ADLER, FELIX B - 9 Aerocynamica 78 African sleeping sickness 62, 63 Air Reduction Campany 44 ALBERTY, ROBERT A 149 ALEXANDER, MATTIE E 121 Alkaloid 41 America first 78 American Association for the United Nations 92 American Chemical Society 94 American Philosophical Society 133 Amino acids 173 Ammonia 61 Ammonium sulfate 119 Amnestic response 127 AMOSS, HAROLD L 68, 93 Amphoteric polyelectroloid 83 Analytical chemical methods 115 Analytical Chemistry 34 Anthrax 157 Antibody 114, 117, 118, 119, 120, 121, 123, 127, 136, 137, 158, 169 185 Antigen-antibody reaction l 72, l 73, l 74 Antisyphilitic 67, 83 Army Epidemiological Board 135 Aromatic amines 62 Arsenic compounds 62, 63 AUERBACH, MATILDA 30, 31 AVERY, OSWALD T. 70, 71, BO, 81, 82, B3, BS, 88, 91, 97, 99, 100, 106, 128, 129 Babies Hoepital 112, 121 Bacterial agglutination 142 Bacterial endocarditia 18 Bacterial specificity 70, 80, 100 BADDILEY, J. 175 BAKER, LILLIAN E. 78 BALDWIN, ROBERT L. 148, 149 BAMBERGER, M. 55 BAUER, JOHANNES H. 136 BEAMS, JESSE W. 132, 133, 136 BEANS, HAL TRUMAN 33 - 35, 40, 46, 48 BEETHOVAN, L. 65 "Behavior of the substance active in pernicious anemia" 78 ~ ­ nal of Biological Chemistrv lxvi (1928] 109 Belgian Ambassador to the United States 64 Belgian Consul General, New York City 64 BENACERRAF, BERUJ 167 166 Benzene 41 Biochemistry 51, 70, 73, 75, 95, 97, 173 Biology 54, 115 BLAKE, f'RANCIS G BS BOGERT, MARSTON T 32, 35, 36, 37, 40, 42 BORDET, JULES 106, 145, 146 BORDET, PAUL 146 BOTTGER, wC, Principlep of Quali­ tative Analveie from the stand­ point of the theory of electroly­ tic d&asoci•tion and law of ma•• actipn [Blakiatont 1906] 40 Botulinum toxins 159 Bouffey agency 21 BOVET, D 68 BRAGG, W J 107 BRAUN, WERNER 165 Bromine 37 Bronx High School of Science 143, 144 BROOKMAN, SAMUEL 104 BROWN, WADE HAMPTON 63, 64 BRYSON, VERNON 165 BULL, CARROLL G 68, 93 BURGESS, JOHN W 52 BUTLER, NICHOLAS MURRAY 34 Calculus 73 CAMPBELL, DANH 171 Carbohydrates 100, 118 187 CARRELL, ALEXIS 66, 77, 78 Castor beans 155, 159 Central Drug Research Laboratory, Lucknow, India 180 Central Park 13 Cerium 43 Cerium oxide 44 CHANDLER, CHARLES f 33, 35 Chemcraft 19 Chemical Abstracts 50 - 51, 97 Chemical Warfare Service 156 - 157 Chemistry of carbohydrates 169, 170 Chemistry Department, Columbia Uni- versity 32 - 37, 39 - 40, 45, 46, 50, 51 Chemotherapy 56, 61, 67 - 68, 69, 71, 72, 141, 154 Chlorophyll 39, 40 Chloroquine 154 CHUBB, PERCIVAL 7 Cinchona alkaloids 94 City College of New York 142, 143 Civilian Conservation Corps Camps 72 CLAIRBORNE, FLORENCE WOLFE 25 CLARkE, HANS T 140 COBURN, ALVIN T 96 COATES, WILLIAM A 152, 153 Coca Cola Company 44 - 45 COHN, ALFRED E 64, 79 COHN, DAVID J 103, 106, 109, 110, 111 188 COLE, RUFUS 60, 74, 83 College of Physicians and Surgeons 68, 140, 149, 157, 158, 162, 168 Columbia College 34 Columbia University 30 - 40, 45, 46, so, 51, 56, 96, 103, 104, 106, 144, 145, 163, 165 Communicable Disease Center 47 Complement 147 - 148, 168, 169 Complement fixation reaction 153 Components of complement 168, 169 Conference on Complement, National Academy of Sciences 147, 148, 149 Conference on lmmunochemistry, OSRD 147 Congo 64 CORWIN, AH 158 Cross-reaction 116, 172 Cyclo-octatetraanes 41 £-womolgus 155 DAKIN, HENRY B 95 Daley's Theater 21 DAVEY, WHEELER P 107 DEKRUIF, PAUL 98, 99 Delafield Hospital 169 Department of Biochemistry, P & S 140, 141 Department of Experimental Surgery, Rockefeller Institute 78 Department of Medicine, P & S 96, 108, 112, 140, 141, 169 Department of Microbiology, P & S 145 189 Department of Pathology, New York University School of Medicine 167, 168 Department of Physiology, Rocke- feller Institute 38 Dermatitis 67 Digitalis 69 Dilution teats 82, 182 DINGLE, JOHN H 135 Diphtheria antitoxin 137 Diphtheria toxoid 127 DNA 129 DOCHEZ, A RAYMOND 81, 83, 85, 103, 113 DOMAGK, GI< 68 Drug resistant malaria 154 Dugway P:rcving Grounds, Utah 159 Eaetman Kodak 138 EBELING, ALBERT H 77 EDSALL, GEOFFREY 175 EHRLICH, PAUL 61, 62, 106, 145 Ehrlich medal 91 EICHELBERGER, CLARK M 92 Electrochemistry 51 Electrophoresis 132, 133, 134 Elementary Chem:i.atry 33 E~LIOTT, JOHN LOVEJOY 9 - 10 Endocarditis 18 Enzymes 39, 51, 63, 69, 136, 148, 174 190 ERICKSON, ANNE M 79 Ethical Culture School 2 Ethical Culture Sunday School 2 Experimental animals 72 FALK, KG 146 FELTON, LLOYD D 68, 71, 72, 122 first World War 83 FISCHER, EMIL 39 FISCHER, MAX 21 fLEXNER, SIMON 45, 46, 59 - 60, 61, 63, 67, 69, 75, BO, 81, 87, 88, 90, 97, 99, 101, 102, 143 formaldehyde 61 fort Bragg 135 FRANKLIN, SUSAN BRAILEY 27 FRANTZ, VIRGINIA K 137, 13B FREUND, JULES 155 FRIEDMAN, JOSEPHS 109 FRIES, MARGARETE 110 FRIESNER, ISIDORE 105 Galactose residues 174, 175 Galacturonic acid 82 Gamma globulin 179 Gas chromatograph 173 GATES, rREDERICK L 73 GAY, FREDERICK P 145 191 General Electric Laboratory 107 GEPPER, _ __ 90 Globulin 117, 118, 119 GOEBEL, WALTER f 85 - 86, 129 "Goethe as a Scientist" 53 Goldwater Memorial Haepital 144 GOLDWATER, S S 101, 105 GOODMAN, JOEL W 136 GOODNER, KENNETH 118 GRABAR, PIERRE 134 Grant•• Tomb 13 GRAY, TT 50 GROSS, LOUIS 102 GROUPIER, VINCENT 165 GROVES, GENERAL LESLIE 162 Guggenheim foundation 130 HAAGENSEN, CUSHMAN D 169 HACKERT, fRED 21 - 22 HANGER, FRANKLIN M 168 HARKNESS, EDWARD 103 Harkness Research Fund 103, 162, 163 HARRINGTON, CHARLES R 95 Harvard University 94 HASTINGS, A BAIRD 73, 74, 94 HAYS, AUSTIN 9B HegJ;th CyJ.ty;&e 12 192 Heart active drugs 69 HEIDELBERGER, CHARLES 19, 169 HEIDELBERGER, DAVID l - 10, 38, 39, 45 HEIDELBERGER, FANNIE CAMPE l - 10, 38 Hemoglobin 7G, 71, 75, 94, 107, 152 HOBBY, GLADYS L 138 - 139 HOFFMAN, ALFRED 54 HOLTZOFF, ALEXANDER 25 HORSFALL, F'RANK 118 Immunochemistry passim Immunodiffusion 134 Immunoelectrophoresis 134 Immunogenetics 172 Immunology 77, 89, 106, 107 Immunology of hemoglobin 71 Immunopathology 172 Industrial Chemistry 33 Influenza B bacillus 121 Influenza meningitis 121 Inklings 29 Institute of Microbiology 104, 142, 164, 165, 166, 167 Institute of Organic Chemistry, Leyden 9l Institute of Paper Chemistry, Appleton, Wisconsin 49 Insulin 95 International Centrifuge Company 76 193 International interests 91 - 92 Ionic theory 34, 40 ISAACS, EDWARD R 165 JACOBS, LAURA 65 JACOBS, WALTER A 38, 39, 40, 45, 56, 61, 62, 63, 64, 65, 66, 67, 69, 71, 73, 76, 79, 93, 94 Johns Hopkins 60, 71, 103, 123, 158, 168 Journal. American Chemical Society 44, 137 JULIANELLE, LOUIS A 156 KABAT, ELVIN A 118, 135, 136, 142, 143, 157, 159, 167 KALISKI, DAVID J 110 KARRAR, P 91 KELLY, HENRY A 2, 26 - 27 KENDALL, E C 51 KENDALL, F' E 113, 114, 115, 142, 143, 147, 156, 171 KESTEN, HOMER D 137 KEYSER, CASSIUS J 30 King of Belgium 64 KLOCK, AUGUSTUS 27 KNEELAND, YALE 120, 168 KOHN, JEROME L 110 KUNITZ, M 157, 158 KUTTNER , THEO. 110 194 Lafayette University 114 LA MER, VICTOR K 145 LAMM, OLLA 132 LAMPEN, JOE 0 166, 167 LANCEFIELD, REBECCA 96 • 97, 100, 101, 129 LANDSTEINER, KARL 71, 75, 76 - 77, 97, 106, 107, 109 LANGMUIR, IRVING 34, 47 - 48, 49 League of Women Voters 92 Lectures in Immunochemiatfv [New York, Academic Preas, 1956] 150. 146 LEE, ELMER 12, 19 LEON, MYRON A 144 LEVENE, PHOEBUS AT 38, 39, 40, 56, 60, 61, 70, 79, 101 LEVINE, LAWRENCE 170 LINDBERGH, CHARLES A 76 LLOYD, LEWELLEN 29 Lobar pneumonia 118 LOEB, JACQUES 60, 66, 98, 107, 168 MACINNES, DUNCAN A 147, 148, 149 MAHARAJAH Of MYSORE 179 Malaria work 98, 149, 150, 151 - 155 MANDELBAUM, FRED 5 105 MANNY, f'RANK A 29 - 30 Man, T~p Unknown [New York, Harper, 1935 346. 78 MARKOWITZ, HAROLD 143 Massachusetts Institute of Tech- nology 148 195 Mathematics 30 - 31, 115, 171 Max Planck Institute for Immuno­ biologie 172 MAYER, MANFRED M 143, 151, 152, 154, 168, 178 Mayo Clinic 157 Mayo foundation 144 MELTZER, SAMUEL J 3B - 39, 60 Metabolism of proteins 128 Metal crystallography 107 Metropolitan Museum of Art 13 METZGER, FLOYD J 32, 34 - 35, 44 Microamino acid analyzer 173 Microbiology 141 Microcomplement fixation technique 170 Microglobulins 118, 136 MILLER, CHARLES P 83 MILLER, EDMUND H 33 - 34 MINOR, EUNICE T 149 MOE, HENRY ALLEN 130 Molecular weight 113, 117, 131, 135, 136 Monkey malaria 150, 156 MORGAN, HUGH J 96 MORGAN, J LIVINGSTON RUTGERS 40, 51 Mount Sinai Ho•pital 101, 102, 103, 104, 105, 106, 107 - 10B, 110, 162 Haunt Sinai Hospital Medical Board 105, 106, 107 Mouse milk factor 169 Mouse protection tests 72, 122 196 MUELLER, J H 82 MULLER-EBERHARD, HANS J 168 MURRAY, HENRY A 95 Museum of Natural History 13 Music 20, 21 MUZZEY, DAVID SAVILLE 7, 27, 52 National Institute for Medical Re- search 95 National Science roundation 162, 163, 165, 167 Nature of the immune reaction 113 NEILL, JAMES M 95 NELSON, JOHN M 35, 36, 37 NEUBERG, C 89, 90 NEUFELD, F' 82 New York Academy of Sciences 147, 148 New York University 164, 167, 168 NICKERSON, WJ 165 Nitrobenzene 40 Nitrogen 41, 82 NITTI, F 68 Nobel Prize 51, 129 NOGUCHI, HIDEY □ 80 Northrop Diffusion Cell 117, 136 NORTHROP, JOHN H 98, 157, 158 NOYES, WILLIAM A 44, 114 Nucleic acid chemistry 61, 79 Nuclear development 162 'II .J 197 OCHOA, SEVERO 148 Office of Naval Research 151, 163, 179 Office of Scientific Research and Development 149, 150, 155, 161 OGATA, TOMIO 179 "On the nature of certain sodium­ uranium compounds" 31 Journal of the Americgn Chemicel Society 1040 (1909) OPPENHEIMER, BS 110 Organic Chemistry 35 - 37, 39 - 40, 45, 46, 54, 56, 59, 70, 97, 107, 115, 146, 165, 172 Organic phosphorous compounds 36 OTTENBERG, REUBIN 109 Oubain 69 OVARY, ZOLTAN 167 Oxidized cotton 137, 138, 139 Oxyhemoglobin 70 PALMER, WALTER W 95 - 96, 103, 111, 112, 140 PAPPENHEIMER, ALWIN M 137 PARKS, WILLIAM H 147 PAULING, LINUS 171, 172, 182 PEDERSEN, EDITH 132 PEDERSEN, KAI 0 130 - 131, 132 Pentavalent arsenicals 62 Pentavalent compounds 62 PEARCE, LOUISE 63, 64 Penicillin 121, 156 Phthalone dye 36 198 Phenylglycine arsenic acid 62, 63 Physical chemistry 40, 51, 54, 115, 132, 133, 146, 155 Physics 53 - 54 Pl. falciparum malaria 151 Pl, vivax malaria 151 PLESCIA, OTTO J 104, 166 Pneumococcal pneumonia 118, 125 Pneumococcus 81, 82, 84, BB, 100, 101, 114, 119, 121, 122, 123 Pneumonic study 64, 68, 72, 83, 68, 117, 118, 119, 120, 122, 123, 124, 125, 126, 127 Poliomyelitis 61, 62, 72 Polypeptide 82 Polysaccharide 72, Bl, 82, 84, 100, 101, 102, 119, 120, 121, 122, 123, 124, 125, 126, 127, 137, 139, 169, 172, 174, 175 Predictions 116 Presbyterian Hospital 103, 104, 108, 117, 11B Princeton, New Jersey 96, 98 Proceedings, National Academy of Sciences 150 Protein antigens 127 Protein-antiprotein systems 169 - 170 Protein chemistry 107, 113, 169 - 171 Proteins 70, Bl, 82, 100, 101, 113, 130, 134 Protozoan diseases 150 Public Health Research Institute of New York 156 Qualitative analysis 34, 46, 47 199 Quantitative immunochemical methods 82, 113, 114, 115, 128 Quantitative theory of the immune reaction mechaniam 115 Quantitative theory of precipitin reaction 116 Quinazolone phthalone 36 Quinezolone problem 36 Quinaline 40 Rabbit antipneumococcel serum 118 RAO, CV N 175 REBERS, PAUL A 115 Refrigerated centrifuge 75 - 76 Rheinhold Publishing Company 148 Rheumatic fever 19 RICHTER, MAURICE N 137 Riein 156 - 160 RITTENBERG, DAVID 155 RIVERS, TOM 83, 84 Rockefeller fellowship 95, 135 Rockefeller roundation 98, 163 Rockefeller Institute for Medical 8, 45 - 46, so, 54, 55, 59, 60, 64, Research 70, 71, 74, 76, 80, 83, 85, 86, 87, 89, 93, 97, 99, 106, lll, 112, 118, 148, 158, 162, 182 Rockefeller Institute Hospital 64 - 65, 73, 74, 81, 83, 101 Rockefeller University 86 ROLr, IDA 93 - 94 ROOSEVELT, ELEANOR 178 ROSENTHAL, NATHAN 109 200 ROUS, PEYTON 60, 66 Rutgers University 104, 115, 142, 163, 164, 165, 167, 169 Ssbbatical eystem, Rockefeller Ins­ atitute 88 - 89, 97 Salmonella e•r•tvphi A 174 Selvarsan 67 Sanitary Corpe, AUS 83 SCHOENHEIMER, R 128 SCHWARTZMAN, GREGORY 102, 108 Secrecy under government contracts 157, 162 Serum sickness 139 SHERMAN, HENRY C 51 SHIVASTRA, D L 181 Silver nitrate 41 SIMONSON, LEE 26 Sioux Falls, N. D. 122, 124, 126 SLODKI, MOREY E 174 SMITH, ADMIRAL 152, 153, 154 SMITH, THEOBALD 96 SOBOTKA, HARRY 109 Sodium 43 Sodium hydro~ide 43 Sodium sulfate 119 Sodium-uranate 43 Spinning top 132 - 133 Squibb 118, 119, 124, 125 201 St. Albans Hospital 144 STARK, WILLIAM E 2, 27, 30 Steroids 52 STETSON, CHANDLER A 167 Stevens Institute, Hoboken, New Jersey 34, 46, 47 STEWART, HAROLD J 19 ... 80 STILLMAN, EDGAR 95 STOKINGER, HERBERT E 145 STOUT, ARTHUR P 137 St:reptococcua 100, 101, 113, 129 Streptococcus muc01ei9 81 ... 82 Streptomycin 164, 176, 177 Stromata 152, 153 Strophanthidin 69 Study of languages 27 - 28, 42 Sugar chemistry 85 Sulfanilemide 68 Sulfa drugs 117, 121, 126 Sulfuric acid 41 Surgeon General of the Army 122, 151, 163 SVEDBERG, T 130, 131, 132 SWIFT, HOMER F 96, 100 Switzerland 54, 55 Symposium on irnrnunochemistry 147 Syphilis 62, 67 ( TAYLC::, 25 202 Teachers Insurance and Annuity Association 87 - 88 THEILER, M 89 Theory of hemolysis 150 The Pneumonia Commission 83, 84 "The quaternary eelta of hexa­ methylenetetramine" 61 - 62 "The volumetric determination of cerium in cerite and monazite" 32 Journal of the American Chem­ ical Sgcietv 642 [1910) 44 THOMAS, CALVIN 53 THOMSON, K JEFFERSON 156 Thyroglobulin 113, 130, 146 Thyroid 113 TISELIUS, ARNE 131, 132, 133 T te de l' mm n te [Masson et Cia, Paris, 1920 106 Transforming substance 129 Treatise on Immunology 147 TREFFERS, HENRY P 128, 141 TAEFOUEL, J 68 Trypanoeome 64 "Tryparaamide" 63, 67 "Trypoeanimide" 63 "Tryposanylamide" 63 TUFTS. FRANKL 53 TURNER, JOSEPH C 120 Typhoid 114 Typhoid becillus 114 203 Typhoid fever 38 Ultracentrifuge 130 - 131, 132, 133, 134 United Nations General Aaaembly 92 University of Illinois 45 - 46, 55, 57 University of Missouri 49 University of Pennsylvania 60 University of Utah Medical School 144 University of Wisconsin 149 Upeele, Sweden 117, 118, 130 - 133, 135 Uranium 43 Uranium compounds 43 US Navy, Bureau of Medicine and Surgery 145, 152, 153, 180 VAN AMRINGE, J HOWARD 30 - 31 Vanderbilt Clinic 112 VANSLYKE, DONALD D 38, 39, 40, 56, 70, 71, 73, 74, 75, 79, BO, 83 - 84, 94, 95 Variability in human response 127 Viet Nam 155 Viet fJam War 164 Viral Study Leborato:r:iss, Rocke­ feller foundation 98 Virginia ham 17 Visitors 89 - 90 VOGEL, HENRY J 165 VON UNWERTH, FREDA 28 204 WADSWORTH, AUGUSTUS B 124 WAKSMAN, BYRON 164 _, WAKSMAN rOUNDATION 176, 177 WAKSMAN, SELMAN A 104, 164, 165, 166, 167, 178 WARBURG, 0 89 Washington Univeraity 156 Waterground Corn Mael 26 WEINTROBE, MAXWELL 143 WELCH, WILLIAM H 60 WELLS, GUY F 27 WELLS, JAMES SC 34 WISE, LOUISE 49, 97 WILLIAMS, CA 134 WILLSTATTER, RICHARD 39, 40, 41, 42, 55, 58, 59, BS, 89, 108 WOHLrARTH, AMELIE 26 WOOD, BARRY 123 WOODBRIDGE, FREDERICK J E 52 Workingman's School 2 World Federation of United Nations Associations 92, 178 X-ray crystallography 107 X-ray pictures 107 X-ray techniques 173 I Yeast galactan work 174 ..... 205 Zeit 8chrift fu; Analvtische Chemie 44 ZINSSER, HANS 82 Zurich 45, 55, 58, 90