00:00:18 The William C. Rose Lectureship in Biochemistry and Nutrition was established on April 14,

00:00:26 1977 to coincide with the 90th birthday of Professor Rose.

00:00:32 This lectureship honoring Professor Rose is presented with love, admiration, and gratitude.

00:00:40 The lectureship is administered by the Nutrition Foundation and supported with funds donated

00:00:45 by the William C. Rose family of former students, colleagues, associates, and concerned institutions.

00:00:54 The lectureship is a tribute to William C. Rose's career of excellence in research and

00:01:00 teaching.

00:01:03 Joining him in this welcoming presentation are Dr. Edwin L. Goldwasser, Vice Chancellor

00:01:09 for Academic Affairs of the University of Illinois, and Dr. M. Daniel Lane, Professor

00:01:16 and Chairman, Department of Physiological Chemistry of the Johns Hopkins University

00:01:21 School of Medicine.

00:01:23 Our moderator is Dr. Carl S. Bestling of the Department of Biochemistry at the University

00:01:30 of Iowa.

00:01:31 It's a pleasure for me to join in this happy occasion.

00:01:38 Particularly as a physicist, I feel a little bit as an interloper in this biochemistry

00:01:42 happening.

00:01:43 But at this university, I consider myself an old-timer.

00:01:47 I came here back in 1951 or so.

00:01:50 And I suppose by that time, Professor Rose was already looking just a few years ahead

00:01:55 to retirement.

00:01:56 But he does represent the highest of the tradition here at this university.

00:02:03 We're a university that has prided itself and still does pride itself as a teaching

00:02:09 and research center, a strong school in research and graduate education.

00:02:13 And Professor Rose's reputation, which I have been exposed to ever since I arrived

00:02:18 here, has certainly been one of strong in teaching and strong in research.

00:02:22 I'd like to know, Professor Rose, how many graduate students are there strung around

00:02:27 the country who received their training and did their research under you?

00:02:30 Do you keep count?

00:02:31 There are 56 PhDs.

00:02:32 And then I had 34 students who received master's degree and did not go on for the doctorate.

00:02:42 And I eliminated all those that didn't have a thesis.

00:02:46 All those master's degree students were all thesis students.

00:02:52 So they're pretty much scattered.

00:02:54 I run into some former students almost everywhere I go.

00:02:59 And it's always fun to be there and see where they are and what they're doing.

00:03:03 I found one boy once, I was sitting in a lobby of a hotel in New York, and this fellow came

00:03:10 up to me and said, do you remember me?

00:03:13 That's always embarrassing.

00:03:15 I said, well, your face is familiar, but I don't remember your name.

00:03:19 He told me his name, and he said he changed over to medicine.

00:03:22 And I said, what branch of medicine are you working in?

00:03:25 He said, pediatrics.

00:03:26 I said, where do you live?

00:03:27 He said, Hollywood.

00:03:28 I said, I didn't know they had babies in Hollywood.

00:03:31 He said, you'd be surprised.

00:03:36 Well, I think if every chemist or every physicist had 56 PhD graduate students, that'd be a

00:03:41 tremendous population explosion.

00:03:45 I'm sure the world is richer for the ones that have studied under you.

00:03:49 I've been very proud of the record the young men and women have made.

00:03:54 They've all done very well.

00:03:57 I was counting the other day, out of that 56 PhDs, 11 are deceased, which seems rather

00:04:04 a high percentage to me, when here I am still going.

00:04:08 Still going strong, I should say.

00:04:11 You didn't teach them well.

00:04:14 It's a pleasure to have you with us today, and I look forward to your lecture a little

00:04:18 bit later.

00:04:19 You were not one of Professor Rose's direct students, I gather.

00:04:22 No, actually I was not fortunate enough to have Professor Rose as my direct supervisor.

00:04:30 However, I had been at Iowa State University before coming to Illinois, and of course I

00:04:38 knew of the reputation of not only Professor Rose, but the outstanding individuals that

00:04:44 he had attracted to the department, and this was one of the major reasons for my coming

00:04:51 to Illinois to study.

00:04:53 In fact, I think I took every course that was offered in the biochemistry department

00:04:57 at that particular time.

00:04:59 Med A at all?

00:05:00 Well, I don't know about that, but one of my best teachers sitting over here on my left,

00:05:07 Dr. Carl Bensley, and also Lavelle Henderson, who really introduced me to some of the things

00:05:14 that I've been involved with over the last 20 years or so.

00:05:20 So, happy to thank you.

00:05:23 I didn't know we could even partially thank you, but we can partially thank you, since

00:05:29 you had our person.

00:05:31 Dan Lane is going to lecture and tell us how you get from acetyl-CoA carboxylase to

00:05:37 insulin receptor metabolism.

00:05:39 I don't expect him to give us a long answer or a short answer.

00:05:42 I hope he'll do it so that I can understand it.

00:05:44 I'll try to keep it short, but there is a connection.

00:05:48 Acetyl-CoA carboxylase is the enzyme that commits the synthesis of fatty acids in complex

00:05:56 lipids.

00:05:59 It is a highly regulated enzyme, and so when that enzyme is activated, the fatty acid

00:06:06 biosynthetic pathway opens up, turns on.

00:06:10 Now, insulin indirectly controls the activity of that enzyme.

00:06:16 More recently, we have gotten into the area of looking at the receptor to which insulin

00:06:24 and through which it elicits the effects on very many enzyme systems, including that involved

00:06:33 fatty acid synthesis.

00:06:35 So, there is a connection.

00:06:37 Well, let me just say this, that as these conversations proceed, having had an official

00:06:43 welcome from the Vice Chancellor for Academic Affairs, who's a level or two above the

00:06:47 rest of us, you understand that physics at Illinois has been one of the great

00:06:53 strengths of this institution, so I would say that, although Ned would not be able to.

00:06:57 And also, chemistry has been a great strength for us, and many of us were glad to see biochemistry

00:07:03 develop here and have a chance to play a part in it.

00:07:08 William C. Rose is one of the pioneers in American biochemistry, both as a researcher

00:07:26 and as an inspiring teacher.

00:07:28 Skilled as a lecturer and blessed with the ability to impart enthusiasm and eagerness

00:07:35 to his listeners, his influence on students, both undergraduates and graduates,

00:07:40 constituted a key contribution to biochemical thought for over 50 years,

00:07:46 40 of them at the University of Illinois.

00:07:50 Many individuals have enjoyed being part of audiences which were captivated by Professor

00:07:56 Rose as a lecturer and public speaker.

00:08:00 Professor Rose began his professional career with graduate studies under the stimulating

00:08:05 guidance of Lafayette B. Mendel at Yale.

00:08:09 After two years at Pennsylvania and six months in the laboratory of Franz Canope

00:08:15 in Freiburg, he joined the medical faculty at the University of Texas in Galveston.

00:08:21 In 1922, he came to Illinois as Professor of Physiological Chemistry,

00:08:28 a title subsequently changed to Professor of Biochemistry in 1936.

00:08:34 At Illinois, he developed fundamental studies of protein and amino acid metabolism,

00:08:41 which led to the discovery of the amino acid threonine and to the concept of

00:08:46 indispensable amino acids in animal and human diets.

00:08:50 He also established quantitative amino acid requirements for nitrogen balance

00:08:56 in human adults.

00:09:00 William C. Rose is one of Illinois' most honored scholars and investigators.

00:09:05 His many awards include several honorary degrees,

00:09:09 a Doctor of Science from the University of Illinois in 1962,

00:09:13 and such major honors as the Osborne Mendel Award of the American Institute of Nutrition in 1949,

00:09:21 the Willard Gibbs Medal of the Chicago Section of the American Chemical Society in 1952,

00:09:28 the 20th Anniversary Scientific Award of the Nutrition Foundation in 1961,

00:09:34 and the National Medal of Science of the United States of America in 1967.

00:09:41 With Mrs. Zula Hedrick Rose at his side for many happy years,

00:09:46 the two Roses exerted a wonderful positive influence on all who knew them.

00:09:52 Absolutely uncompromising in matters involving integrity and sincerity,

00:09:58 William C. Rose has personified many of those qualities of loyalty,

00:10:04 unselfishness, and friendliness which mark the unusual individual.

00:10:11 Colleagues who will participate in conversations with William C. Rose are

00:10:16 Dr. Herbert E. Carter, Research Fellow, Office of Arid Land Study, University of Arizona.

00:10:24 Dr. Carter became the second member of the faculty of the Biochemistry Division

00:10:29 when he joined Professor Rose in 1932 at Illinois.

00:10:34 Dr. Carl S. Vestling of the Department of Biochemistry, University of Iowa.

00:10:40 Dr. Vestling was the third member of the Biochemistry Division at Illinois.

00:10:46 Dr. Lavelle M. Henderson, Professor of Biochemistry, University of Minnesota.

00:10:53 Dr. Henderson was the fourth member of the Biochemistry Division at Illinois.

00:10:59 Dr. Minor J. Kuhn, Professor and Chairman, Department of Biological Chemistry, University of Michigan.

00:11:08 Dr. Kuhn was the first William C. Rose lecturer in Biochemistry and Nutrition in 1978.

00:11:16 And Dr. William J. Darby, President of the Nutrition Foundation,

00:11:22 Professor and former Head of Biochemistry, Vanderbilt University.

00:11:28 Now we'll turn and ask Dr. Rose to talk a bit, but first, Bill, I'll turn the discussion over to you.

00:11:34 Dr. Rose, we just heard that you received the Osborne-Mendel Award,

00:11:40 which indeed was the first time the Osborne-Mendel Award was given.

00:11:44 That was in 1949. It was given to the American Institute of Nutrition,

00:11:50 and it therefore was very fitting that you should be the first recipient.

00:11:59 Fitting for two reasons.

00:12:01 Dr. Glenn King, who then was President of the Nutrition Foundation, which supports that award,

00:12:09 commented, in fact he wrote in the history of the Nutrition Foundation,

00:12:14 the following statement concerning you.

00:12:16 No other scientist has a record comparable to that of Dr. Rose

00:12:21 in identifying and establishing the quantitative requirements for so many essential nutrients.

00:12:27 His work on amino acids stand as a classic in the field of nutrition and for the benefit of man.

00:12:34 I think that's one reason, one good reason.

00:12:38 The other is that you were a student of Professor Mendel at Yale,

00:12:47 and I wonder if you could recall for us some of your experiences

00:12:51 or some of the qualities of Professor Mendel and some of your associations there at Yale.

00:12:57 Yes, I arrived at New Haven in the fall of 1907,

00:13:05 and after the usual interview with the Dean of the Graduate School,

00:13:09 I was instructed to go to Professor Chittenden's office,

00:13:14 who was Director of the Sheffield Scientific School at the time,

00:13:17 and he or someone designated by him would make out my study schedule.

00:13:24 So I went over, the gentleman received me very cordially,

00:13:28 and asked me by business why I was coming to see him.

00:13:33 Well, when I explained that I was the head of the Graduate College,

00:13:37 his first question was, how old are you?

00:13:40 And I admitted that I was 20 years old.

00:13:43 He said, well, I'm a freshman, I'm 19 years old.

00:13:46 I think you ought to enter the senior class.

00:13:51 I said, well, Professor, I can't do that.

00:13:54 The first place I've been accepted by the Graduate College,

00:13:57 I've been given a scholarship that covers my tuition and laboratory fees,

00:14:01 and I simply cannot afford to pay the tuition required of undergraduate students.

00:14:07 He said, well, do you know what tryptophan is?

00:14:10 That was the question.

00:14:12 Now, if you look in the history of the amino acids,

00:14:15 you'll find that tryptophan was discovered in 1905, as I remember, 1905.

00:14:23 Its formula then wasn't quite correct.

00:14:26 Its true formula wasn't established until a year later.

00:14:30 It had not gotten into the textbooks in 1907.

00:14:33 So I said, no, Professor, I don't know what tryptophan is,

00:14:36 but if you give me a few days to review my organic chemistry, I think I can pass it.

00:14:41 He says, that won't be necessary.

00:14:43 I'll turn you over to my right-hand man.

00:14:45 He'll soon find out what you know.

00:14:48 That was the reception I had from him.

00:14:51 With that, he got up and escorted me across about 100 yards of lawn

00:14:56 to the old Sheffield home where the Department of Biochemistry was housed at that time

00:15:03 and introduced me to Dr. Manning.

00:15:06 I must say that on that little trip, which seemed to be about an hour long,

00:15:12 I wasn't very happy.

00:15:14 I wondered if I was making a mistake.

00:15:16 But when I got to Dr. Manning, I was left in his care.

00:15:21 The atmosphere changed immediately.

00:15:24 He was a very gentle, kindly man.

00:15:27 He went over my previous training with great detail, made notes as he went along.

00:15:33 And finally, when he concluded, he had already made up in his mind what courses I should take.

00:15:40 I hadn't had any biology.

00:15:42 I didn't think biology was necessary for a chemist.

00:15:45 And I'd majored in the chemical sciences and physics and math and things of that sort.

00:15:51 He said, well, you must take biology to be a biochemist.

00:15:54 But I said, you haven't really decided what you want to do yet?

00:15:57 I said, no.

00:15:58 I've enjoyed every course in chemistry I've had, so I don't know which one I like best.

00:16:03 And he said, well, suppose we make out a general schedule

00:16:08 and give you a year in which to make up your mind.

00:16:12 In the meantime, you can get off all required courses

00:16:16 and you can decide whether or not you want to be a biochemist or some other area of chemistry.

00:16:22 Well, that conversation that I had with him changed my whole attitude towards graduate work.

00:16:30 And my devotion to him, which began then, increased as the years went on.

00:16:36 He was a marvelous teacher, a marvelous personality, and, of course, a great research man as well.

00:16:44 So then I don't know how I could have chosen a more acceptable place.

00:16:48 After one semester in his course, I had no longer any doubt as to what I wanted to do.

00:16:54 I decided I wanted to be a biochemist, largely because of his influence.

00:16:59 I could go on for hours with thoughts about chemistry, but I won't.

00:17:04 Well, he obviously was a very great teacher and a great influence on the lives of his students.

00:17:09 My own graduate mentor, Dr. Howard B. Loyce, was also a student of his and an associate of yours at Yale,

00:17:18 and I believe at Pennsylvania, are here.

00:17:21 He succeeded me at Pennsylvania, and then I succeeded him at Illinois.

00:17:26 And now Maynard Kuhn is in his position at the University of Michigan.

00:17:32 That's right.

00:17:33 He was also at Pennsylvania at one time.

00:17:38 Well, this gets us off to a good start.

00:17:40 This doesn't surprise us.

00:17:41 In one word, why did you happen to come?

00:17:43 How did we persuade you to come to Illinois from Galveston?

00:17:47 Well, it didn't require any thought to answer that question, Carl.

00:17:51 It was the reputation of the chemistry department.

00:17:54 I came to Illinois at the same rank and the same meager salary I'd been getting at the University of Texas for two or three years,

00:18:05 and the thing that attracted me was the reputation of the chemistry department.

00:18:10 I felt then, and I've never had any reason to change my mind, that this department of chemistry was one of the best in the world,

00:18:18 and as far as I was concerned, it was the best in the world,

00:18:22 and I thought it would be a wonderful opportunity to be associated with such a group of men.

00:18:27 I've never regretted that change.

00:18:32 Well, you know, I came to Illinois in 1930 also because of the reputation of the chemistry department,

00:18:40 and I came as a graduate student in organic chemistry,

00:18:44 but my mentor, Carl Speed Marvels, said,

00:18:48 well, you know, you really should take a course in biochemistry,

00:18:52 and after two of your lectures, I no longer had any doubt what I wanted to do eventually,

00:18:58 but, you know, I had quite a long contact with Roger Adams, who was head of the department in a variety of different ways,

00:19:04 and it's occurred to me on more than one occasion to wonder how long it took you.

00:19:09 You converted me to being a biochemist in two lectures,

00:19:12 but it must have taken more than that to convert Roger Adams to think that biochemistry had a real place in the chemistry department.

00:19:19 Yeah, really, I don't think that you could pick out any spot or any time when that happened.

00:19:24 It was a gradual process.

00:19:26 But I do remember one event that bore on this problem,

00:19:31 and that was the visit of Dr. Ruzicka of the University of Zurich,

00:19:38 who came, I don't remember the year, but it was during the administration of President Willard.

00:19:45 That goes back a good while.

00:19:47 And he had just been to Harvard to receive an honorary degree,

00:19:52 and Roger asked him one day, he said, well, they were talking about the formality and connection with it,

00:19:58 and Ruzicka said, they asked me what area of chemistry I wanted to be designated on my award certificate.

00:20:07 And Roger said, well, you said organic chemistry, didn't you?

00:20:10 Oh, no, he said, I'm a biochemist.

00:20:12 Well, Roger never got over that.

00:20:15 He brought it up over and over.

00:20:17 I knew Ruzicka called himself a biochemist.

00:20:20 And some of Roger's colleagues brought it up over and over, too.

00:20:24 I remember hearing them needle Roger.

00:20:26 So apparently Ruzicka, who of course, as you remember, did synthesize some of the male sex hormones, testosterone, among others, maybe others,

00:20:38 had gotten to the point where he was more interested in the application of this organic chemistry to biochemical properties

00:20:45 than he was in the synthetic organic region.

00:20:52 Well, Dr. Rosen, when I came to Illinois in 1948, fresh out of graduate school,

00:20:58 I thought the best thing I could do before I taught the lab to your course was to listen to your lectures.

00:21:04 So I started listening to them, thinking I'd be in there two or three weeks to get oriented,

00:21:10 and I ended up attending every lecture for the entire semester.

00:21:15 Did you enjoy teaching as much as you seemed to?

00:21:19 Yes, I did.

00:21:20 You may recall that I never was willing to entirely give up the elementary course.

00:21:25 I taught the elementary course in one semester as long as I was there.

00:21:30 And the thing I enjoyed most of all of the formal teaching was chemistry 4.50, I believe was the number,

00:21:39 the advanced course on intermediary metabolism.

00:21:42 There was no textbook on that subject at that time.

00:21:46 And I used to spend hours bringing that up to date.

00:21:50 What I did was to make an outline, a very brief outline of what I was going to discuss on a 4x6 card.

00:21:57 And I'd keep that until next year, and then I'd see what I should add to bring it up to date,

00:22:03 and remodel and make out a new card.

00:22:05 That's the way it went.

00:22:06 So it took me about three to four hours of work at home every lecture I gave.

00:22:12 I don't think students ever realized how hard I worked on that course.

00:22:17 But it was the only way I had to dig this thing out of the literature.

00:22:21 But it was a fascinating topic, and I thoroughly enjoyed it.

00:22:26 And, of course, best of all, it was a great instruction.

00:22:30 I just loved being with these boys who, like Monotone there, still a boy.

00:22:37 All relatives.

00:22:40 And watch them do their work in the laboratory, and then watch their progress after they left.

00:22:47 It's been a great satisfaction.

00:22:49 All of that preparation you did showed when you went to the lecture room.

00:22:53 It was flawless.

00:22:55 Let me stick my nose in there for just a minute.

00:22:57 Here's a question that Dr. Kuhn would not ask.

00:23:00 I'll ask it.

00:23:01 Can you imagine a better set of graduate students than, for example,

00:23:06 Julius Johnson, Bill Haines, Jim Cade, or Myron Kuhn to mention several?

00:23:11 May I go ahead with my question?

00:23:12 No, no.

00:23:13 You've got to answer that question.

00:23:15 No, I can't imagine if I had a group of students.

00:23:18 And I had others that were fine, too.

00:23:21 Even way back when I first came, among my first students was W.E. Bunny,

00:23:26 who later became Vice President of Squibb.

00:23:29 And Gerald Cox, who's still, as far as I know, alive and is in Pittsburgh.

00:23:36 And then a little later was McCoy, Dick McCoy, and Curt Meyer, both very brilliant students.

00:23:47 All these boys made straight A's and did a fine job in research.

00:23:52 So all the way through, I've had marvelous students.

00:23:57 If one couldn't get good research done with those boys, he's hopeless.

00:24:01 You probably recall when I joined your laboratory,

00:24:05 you were already studying the amino acid requirements of man.

00:24:09 And I, among others, became human guinea pigs,

00:24:12 ate these diets of rather expensive crystalline amino acids,

00:24:16 what we might call sawdust for roughage.

00:24:19 We had butter fat, which was almost like axle grease.

00:24:23 It was the flavorless part of the butter.

00:24:25 We had a vitamin pill about so long that it contained any vitamins in the liver,

00:24:34 perhaps not yet isolated.

00:24:36 And it had the unusual combination of liver flavored with powdered sugar and peppermint.

00:24:43 And I recall being on these diets, and the only variety really was the amount of sawdust and still water.

00:24:50 Everything else was fixed.

00:24:52 And I must say, at times I wondered, how in the world did you ever get into this kind of research?

00:24:57 Would you tell us what really intrigued you so much about animal amino acid requirements

00:25:04 and then those of man?

00:25:06 Well, that's a long story.

00:25:09 It began with the first time I saw an animal deprived of histidine, losing weight very rapidly.

00:25:19 And I put just the tiniest bit of histidine in that diet.

00:25:23 And immediately, the next morning, he was going up.

00:25:26 It was the most spectacular change in attitude I'd ever seen.

00:25:30 I'd never seen anything like it.

00:25:32 I'd never seen animals deprived of essential components.

00:25:36 And then what happened when you returned them before?

00:25:39 And immediately I said, well, for goodness sake, I'd like to know if other amino acids behave like this,

00:25:45 if they induce such marvelous change.

00:25:48 And as I thought over it a little longer, I thought, well, it's been 10 years since the last...

00:25:54 The work of Arvin Mendel, where they discovered that lysine and tryptophan were essential components,

00:26:02 has been 10 years, and there's only been one amino acid, histidine, that's found to be essential since that time.

00:26:10 And that was somewhat contaminated with the idea that it was interchangeable with arginine.

00:26:17 Why don't I start in and test the rest of the amino acids?

00:26:21 And in my youth and enthusiasm, it never occurred to me I might not be able to do it.

00:26:27 I just went ahead and we tried first with hydrolyzed produce from which we remove various components

00:26:35 as well as available methods would permit.

00:26:38 And the animals would grow with such a diet, like taking out the prolines, both of them,

00:26:43 or taking out glucanic acid, they'd grow partly without any influence on the growth at all,

00:26:49 and then I wondered, is that because these things are not essential components of the diet?

00:26:55 Or are they growing because they're traces of these things I hoped I'd remove still there?

00:27:00 And I knew there were traces left in them.

00:27:03 And so it came to the point where it seemed to me if we're going to make any progress at all,

00:27:08 we'd have to use mixtures of highly purified amino acids.

00:27:12 The only way we could answer the question.

00:27:15 And that's what we set out to do.

00:27:18 Did you have to extend it to your graduate students, those human game pigs?

00:27:23 Oh, oh.

00:27:25 Well, that was sort of the ultimate result of the animal experiment.

00:27:31 If you find out what the animal requires, you naturally want to know how does this apply to man.

00:27:37 But the real turning point was in a meeting of Glen King's scientific advisory committees.

00:27:45 He called this group of men who looked over the application for grants in those days.

00:27:53 I think you had the same sort of a group, but you called it a little different, by a little different name?

00:27:57 Scientific Advisory Council now, just changed one word.

00:28:00 I see.

00:28:01 Well, we were sitting there and we discussed various applications,

00:28:05 and Glen said, you know, I wish somebody would do human work like Rose is doing with animals.

00:28:14 And nobody said anything.

00:28:16 I said, if you give me $15,000, I'll do it.

00:28:19 That was the rashest thing I ever said.

00:28:22 And he said, get out of this room so we can talk about it.

00:28:27 So I walked out of the room, and I'd hardly gotten out before they sent somebody to bring me back in.

00:28:33 They said, we'll give you the $15,000.

00:28:35 Well, he didn't know what he was getting into, and I certainly didn't know what I was getting into.

00:28:40 But it required a lot more than $15,000 to do the work that year.

00:28:44 And in the course of the entire project, I'm sure that the Nutrition Foundation provided in excess of $100,000 for this work,

00:28:56 in addition to what I was getting from the university.

00:29:00 But that was the way I got into that.

00:29:03 And it was quite an investigation to formulate a diet.

00:29:08 We worked for months on that, and with the aid of my good wife who did some kitchen baking experiments

00:29:16 to see how we could mix things into a wafer that would be edible.

00:29:23 One day, I remember walking in the house one afternoon after being in the laboratory all day.

00:29:29 She said, oh, I made a discovery.

00:29:31 I said, oh, have you? What is that?

00:29:33 She said, I've discovered how a new method of making synthetic rubber.

00:29:40 No comment.

00:29:42 You comment.

00:29:45 Eventually, we worked out a method that I don't think was too bad.

00:29:50 You had your amino acids flavored with lemon juice.

00:29:54 So it was just like bringing a lemonade.

00:29:57 Of course, bringing it every day wasn't quite what you would choose ordinarily.

00:30:02 And the wafers were quite edible.

00:30:05 You did get a little tired in the course of time.

00:30:07 We took the vitamins in pill form.

00:30:10 I don't remember using any liver.

00:30:12 We did use some yeast extract.

00:30:15 Maybe that's what you had in mind.

00:30:16 I don't know.

00:30:17 Maybe we did use liver.

00:30:18 I don't remember.

00:30:19 But the total unknown nitrogen was very low in those vitamins.

00:30:23 And we first found that the boys could eat it.

00:30:27 And second, that they came into nitrogen equilibrium with quite a key to some of that.

00:30:32 And once we decided that, the rest of it was clear sailing.

00:30:36 Dr. Rose, I very often wondered how you were able to get sufficient of the crystalline amino acids

00:30:48 even for the rat experiments in the early days,

00:30:51 knowing what a laborious task it was to isolate and purify individual amino acids

00:30:58 back in the period of the 30s, the early 30s and the 20s.

00:31:04 Well, along in the early 30s, which of course were depression years,

00:31:11 I went to New York at my own expense.

00:31:14 The university didn't pay my way.

00:31:16 I spent three days there begging, going from one foundation to another.

00:31:20 I think that was before the Nutrition Foundation had been established.

00:31:24 And I got the same story.

00:31:27 I began with the Rockefeller Foundation because I happened to know Dr. Pierce,

00:31:32 who was the man in charge of the grants,

00:31:35 and he'd been on the faculty in Pennsylvania when I was a young student as a instructor at the end.

00:31:42 And so I knew him quite well.

00:31:44 And my dean at Texas had recently left the University of Texas

00:31:50 and had come to work for the Rockefeller Foundation

00:31:55 and was put in charge of the medical education in the Far East.

00:32:00 He spent most of his time in China and Singapore and Japan, other oil countries.

00:32:07 But he was in town, and he's the man who gave me a list of the foundations I was to visit on that occasion.

00:32:13 I got the same story in each foundation, namely,

00:32:16 that the yield on their investments had dropped so during the depression

00:32:20 that they were worried about how they could meet their obligations, their commitments already,

00:32:25 and that they couldn't consider making any further commitments.

00:32:31 So I went home without a cent and very much disappointed.

00:32:35 Then I rolled around.

00:32:36 I asked the University Graduate School to give me a grant.

00:32:40 I bet you can't guess how much they gave me.

00:32:42 They appropriated fifty dollars from me.

00:32:44 Fifty dollars?

00:32:45 Fifty dollars.

00:32:46 Five-oh.

00:32:47 And I wrote to the AMA, and they gave me, I think it was a hundred.

00:32:53 I wrote to the headquarters of the American Pharmaceutical Society.

00:32:59 I've forgotten the exact name of it because it had headquarters in Boston at the time.

00:33:05 I wrote to everybody I could think of, and I collected three hundred dollars.

00:33:10 And I hired students at forty cents an hour to work in the laboratory

00:33:15 and make the amino acids that you could prepare better by isolation than by synthesis.

00:33:21 Then the organic people, Dr. Adams and Dr. Marlowe, would synthesize the others,

00:33:29 things like glycine, alanine, serine, cysteine that you can make synthetically better

00:33:37 or more readily than you can by isolation.

00:33:40 So that's the way I accumulated the amino acids for the first experiment.

00:33:44 The sad part is that I used all of those amino acids that we had made

00:33:51 and a video of the synthetic amino acids on the first feeding experiment

00:33:56 to demonstrate that when you put all known amino acids in an otherwise adequate diet,

00:34:01 the animals would go downhill.

00:34:03 I knew something was wrong.

00:34:06 There were three or four experiments, maybe more, in the literature

00:34:10 describing attempts to feed diets containing amino acids in place of proteins,

00:34:16 but no one had ever used a diet containing all of the known amino acids before.

00:34:21 Indeed, some of them were carried out before methionine was discovered.

00:34:26 And I think, invariably, the authors concluded that the reason the animal wouldn't grow

00:34:34 was because the amino acids taste so bad that they wouldn't eat them.

00:34:38 In other words, it's purely a taste.

00:34:41 That didn't impress me because I'd already hydrolyzed some protein.

00:34:46 That breaks the whole mess down and supplements it with tryptophan,

00:34:49 which of course would destroy vasodendrosis, and animals would eat that.

00:34:53 It all plays a role.

00:34:55 So I wasn't impressed with the taste idea.

00:34:58 It seemed to me much more likely that there was something in proteins that were not known,

00:35:05 and so we set out to try to find it.

00:35:08 That's the way we got into that.

00:35:10 And isn't that what's in the threonine, which eventually came out of this water?

00:35:14 That was the result.

00:35:16 It's the bottle that you're showing to Herb Carter.

00:35:19 I think I've shown Herb some of the first threonine that was isolated.

00:35:22 I think that's the book I teach you about.

00:35:24 You remember?

00:35:25 It should be pointed out that Herb Carter did the synthesis, the chemical-organic synthesis of threonine.

00:35:30 Yeah, he did the synthesis.

00:35:32 Probably some of the physical characterizations.

00:35:34 Whenever you smell a tube of alcohol, doesn't it take you back to that fourth floor of the noise lab

00:35:39 where those darn 40-gallon crocks were standing there being stirred summer day after summer day, extracting them?

00:35:45 Extracting them as we do now.

00:35:48 It should be pointed out that these pictures that you may be able to see

00:35:51 are of our honoree at various stages in his career.

00:35:55 He's sitting in a motorboat here.

00:35:57 He didn't spend his whole life in a motorboat, but he and I had a ride together in that same boat.

00:36:02 I can't tell if it's behind me here.

00:36:04 What are you eating there, Will?

00:36:07 I don't know what that is.

00:36:09 I don't remember.

00:36:10 It looks like it's good.

00:36:11 It's not synthetic at all.

00:36:13 It looks like chardonnay, bone and amino acids.

00:36:16 I want to ask Dr. Kuhn one question.

00:36:19 Which amino acids were you deprived of?

00:36:22 Several.

00:36:23 I think I had the record of being the longest number of days on these diets.

00:36:27 Although I do joke about what we went through,

00:36:31 and I must add that those of us who ate together in this room had pinups.

00:36:35 We would cut out photographs of food and put it on the wall to indicate where our interests were.

00:36:41 We were very impressed by the importance of this to man,

00:36:45 and, indeed, several important things did come out of the work,

00:36:48 including the finding that histidine is not required by adult man,

00:36:53 but is required by most other higher species.

00:36:58 So it surely was important both from a basic point of view and a nutritional point of view to the human species.

00:37:05 You know what I remember?

00:37:06 I was the confidant of some of the students,

00:37:10 and they were not told when a given amino acid was removed.

00:37:14 So these were blind experiments.

00:37:16 And I remember several of them telling me,

00:37:18 I can't eat it anymore, within a day or so, when the amino acid had been removed.

00:37:25 Failure of appetite is just as prompt and effective as the loss of weight in an animal.

00:37:32 It just comes on very quickly.

00:37:34 And I remember it was either Bill Haines or Julius Johnson,

00:37:40 they were carrying out experiments at the same time,

00:37:43 came in one day and said,

00:37:45 and he said, he was one.

00:37:47 He came in and he told me, he said, I can't do this anymore.

00:37:50 I said, now listen, fella, if you just carry on one more day,

00:37:54 you're going to feel better.

00:37:56 I didn't want to tell him what was going to happen.

00:37:58 He might have judged what was going to happen.

00:38:00 But one more day, and we put the compound that he was proud of,

00:38:04 the next day I think it was serine,

00:38:06 put it back in the diet,

00:38:08 and he was in an entirely different mood after that.

00:38:12 There is a psychological effect of the deficiency in the diet.

00:38:17 I recall one of your students, I won't name him for obvious reasons,

00:38:21 who went out and had a steak dinner with his friends one evening

00:38:26 celebrating his getting on the diet,

00:38:28 because he thought he'd be on it for weeks.

00:38:30 And it was so bad that he went out the next evening

00:38:33 and celebrated getting off the diet by having another steak dinner.

00:38:37 He couldn't take it.

00:38:40 He didn't have any character.

00:38:42 We had two or three men who thought they couldn't take it.

00:38:47 I wanted to carry out a few experiments on women too.

00:38:51 And we had two girls who put on the diet.

00:38:55 I won't mention their name either, but they gave up after one day.

00:39:00 And yet, most of them didn't complain to me much.

00:39:05 Maybe they complained to Carl.

00:39:07 Not very much. Just a little.

00:39:09 There was one boy, an organic, who was having a minor in biochemistry,

00:39:15 so he was fully aware of what he had to do and how important it was

00:39:19 not to lose any of the excreta underneath the quantities of what was set before him.

00:39:24 He was perfectly aware of that.

00:39:26 But he was on the diet over and over and over again,

00:39:30 and with different amino acids.

00:39:31 I remember once he came in and said,

00:39:34 I said,

00:39:43 Well, we just got a dollar a day on all we could eat, didn't we?

00:39:46 Yeah, a dollar a day.

00:39:47 Something that should have been brought in.

00:39:49 Well, first we started off with a dollar a day.

00:39:50 I had to raise that into two dollars a day.

00:39:52 I remember it was two dollars.

00:39:54 But, so they were saving quite a bit of money.

00:39:58 They didn't have any more to pay.

00:40:00 You could always identify the people that were currently on diets

00:40:04 by either they were munching on that cracker

00:40:07 or they had crumbs down the front of their shirt.

00:40:10 Yeah, I'm sorry about that.

00:40:12 They lost some of their knowledge.

00:40:16 Not very many crumbs.

00:40:17 Very fine crumbs.

00:40:18 Very fine crumbs.

00:40:22 Well, I want to ask you one other question, Will,

00:40:24 and that is, when you were working on threonine,

00:40:26 did you have any idea of the future development of biochemistry?

00:40:30 Or have many of these things come as a surprise to you as they have to me?

00:40:34 Yes, most of the things have come as a surprise.

00:40:38 I recognized, I think, that we'd be able to determine

00:40:42 the sequence of amino acids in codons.

00:40:45 Noises from Devino's work on

00:40:47 pituitary hormones?

00:40:50 Oxytocin.

00:40:51 Oxytocin.

00:40:52 Oxytocin.

00:40:53 And that seemed...

00:40:55 I had no conception of what was going to happen in the nucleic acid field.

00:41:00 Not the slightest conception.

00:41:02 I thought that the P.A. Levine formula,

00:41:05 which consisted of the union of four nucleotides,

00:41:09 was nucleic acid.

00:41:10 That was it.

00:41:11 That was as complicated as it was.

00:41:14 Complex as it was.

00:41:16 It never occurred to me that the sort of thing we know now is true

00:41:21 Well, we could continue these conversations

00:41:25 as long as you would wish us to

00:41:28 or I know the audience would want us to.

00:41:30 But I have a feeling that maybe we ought to begin to move toward a conclusion.

00:41:34 And I was talking to Bill Darby a bit ago

00:41:38 and on the occasion of your 90th birthday,

00:41:42 the starting of the lectureship,

00:41:45 there was a particularly interesting statement made,

00:41:47 I guess it was by Bill Haynes.

00:41:49 Is that right?

00:41:50 Yes.

00:41:51 Would you give us that?

00:41:53 Yes.

00:41:54 Bill Haynes, another student that Dr. Rose has mentioned here

00:41:59 and has come out several times in the conversation here,

00:42:05 summarized, I think, at the end of the dinner for Dr. Rose,

00:42:12 what he wrote as a consensus.

00:42:16 I think it is appropriate to read this.

00:42:19 Dr. Rose enhanced the quality of life for his students

00:42:23 by encouraging and supporting those things which enriched the mind and spirit.

00:42:28 Good character was the essential raw material.

00:42:31 Good taste was the product.

00:42:34 His personal dedication to the highest quality of performance

00:42:37 was projected in his wise counsel.

00:42:40 For all of this, he demanded nothing in return

00:42:44 except excellence in performance and behavior

00:42:47 of his academic children and their children,

00:42:50 the latter whom he considers to be his academic grandchildren.

00:42:55 Yes, Dr. and Mrs. Rose do indeed have a large and grateful family.

00:43:01 I feel that this gives something of the flavor

00:43:06 of one of the greatest teachers of biochemistry

00:43:10 and obviously as well one of the greatest investigators.

00:43:14 And it is our hope that this lectureship

00:43:20 and its sponsorship will indeed remind annually

00:43:27 the younger people in science of those great qualities

00:43:31 that have characterized Dr. Rose

00:43:34 and which I think we got just a bit of flavor of, Dr. Rose, this afternoon

00:43:40 that you have in a sense patterned some of these

00:43:47 maybe after those characteristics that you mentioned in Dr. Mendel.

00:43:52 I think it is very likely that I have tried to imitate him

00:43:56 because certainly he was the man I looked up to most.

00:44:01 My association with him lasted as long as he lived.

00:44:05 He died quite young, relatively speaking, after a long illness.

00:44:12 I've forgotten, I think it was 1935.

00:44:17 But he was a very inspiring teacher and friend.

00:44:23 And so I think unconsciously one would be inclined

00:44:30 to try to imitate those qualities which he demonstrated so beautifully.

00:44:34 And you have passed those on to many of your students because I've seen it.

00:44:38 It's time for us to conclude our conversations with Bill Rose,

00:44:41 distinguished scientist and a marvelous human being.