00:00:00 Your first president of the, is it the endocrine society or endocrinology, endocrine society?

00:00:13 First woman who was president.

00:00:14 All right, I'm going to cue you.

00:00:15 Okay.

00:00:16 I'm just going to go like that.

00:00:17 All right.

00:00:18 Okay, quiet on set.

00:00:40 Hello, I'm Helen Free from Miles Laboratories in Elkhart, Indiana.

00:01:04 We're here today to do an eminent chemist interview with Dr. Rosalyn Yalow, the Nobel

00:01:10 Laureate in Medicine from 1977.

00:01:13 Dr. Yalow is here in the Bronx of New York, and we're going to ask her some questions

00:01:18 about her early life.

00:01:20 Dr. Yalow, I understand that you were born in New York City and have lived here all your

00:01:25 life.

00:01:26 Would you tell us a little bit about growing up in New York and about your parents and

00:01:30 family?

00:01:31 Well, I'll be even more specific than in New York.

00:01:36 Except for three and a half years in graduate school, I have almost always lived in the

00:01:41 Bronx.

00:01:43 My father was born in the Lower East Side.

00:01:47 He and his younger brother were born in the States.

00:01:52 The older children were born in almost every country as they came from Europe.

00:01:57 My mother came from Germany when she was four years old, lived in New York and Philadelphia

00:02:05 for a very short time, and then went to a small town in Ohio, Wellsville, Ohio, population

00:02:11 2,000.

00:02:13 When she became of marriageable age, she returned to New York.

00:02:18 Neither my mother or father had much education.

00:02:20 My father went through eighth grade, my mother through sixth grade, and went to work.

00:02:26 On the other hand, they certainly expected my older brother and me to go to college.

00:02:33 Some of my early memories date back to my being a sort of an aggressive child in spite

00:02:40 of having an older brother.

00:02:42 On the other hand, my brother and I in many ways were quite close.

00:02:46 It was his responsibility to take me to the library.

00:02:51 I joined the library on my fifth birthday.

00:02:56 You had to be able to read a sentence and sign your name, and I was all geared up for

00:03:01 it.

00:03:02 They wouldn't let you join the library before the fifth birthday in those days.

00:03:07 My house never really had any books in it.

00:03:09 We were not that comfortably fixed.

00:03:13 On the other hand, it was my brother's responsibility every week to take me to the library to turn

00:03:18 in already read books for new ones to be read.

00:03:25 Both Allie and I were very avid readers very early.

00:03:28 Did he choose the books or did you?

00:03:30 Oh, I chose the books.

00:03:31 Nobody would choose anything for me.

00:03:34 You were a stubborn child, I gather.

00:03:36 I have a reputation of having been a very stubborn child.

00:03:40 One of the things that my mother and I both recall, so it probably happened, is that she

00:03:48 was taking us home from a motion picture theater where they also had Bodeville.

00:03:56 She wanted to walk one way and I wanted to walk another way.

00:04:00 I must have been all of about three.

00:04:03 I sat down and wasn't going to move.

00:04:07 The crowd gathered around and my mother decided we had to walk my way or she was going to

00:04:11 be too embarrassed to deal with it.

00:04:13 An early tantrum.

00:04:17 Are you still stubborn?

00:04:20 In certain ways.

00:04:22 In other words, I'm not stubborn.

00:04:23 I'm very flexible in many things.

00:04:26 But when I decided something has to be done, I carry it through.

00:04:32 What kind of games did you play when you were a child?

00:04:34 Were you a leader even back in those days?

00:04:38 I really don't remember very much about friends from early childhood.

00:04:43 We moved from my old neighborhood, which was in the East Bronx, when I was eight.

00:04:53 And we moved then to the West Bronx.

00:04:55 I really remember little about friends in these early years.

00:05:00 I think part of it was that in the New York City school system, if you were bright you

00:05:06 skipped grades.

00:05:09 I had already skipped two grades by the time we had moved.

00:05:15 So I didn't have this building of friendships of people that I went to school with.

00:05:21 What made you first decide to be a scientist?

00:05:24 What or who influenced you that way?

00:05:27 Part of it is that I'm not good at a lot of things.

00:05:31 I can't sing.

00:05:32 I was always a listener.

00:05:34 I'm not very athletic.

00:05:36 When I was taken to dancing school, I was sort of cloddish.

00:05:41 Interesting enough, I had no talent in languages.

00:05:44 My grandmother spoke German to me until she died when I was 10.

00:05:48 And I understood German very well, but could never speak German.

00:05:53 So that left sort of two fields of potential interest.

00:05:57 One was history, which was the field my brother chose.

00:06:01 And I ruled against history when I read an English book about the American Revolution.

00:06:08 And I compared it with American books about the American Revolution.

00:06:11 And then I decided there's no truth in history, it's just a matter of who writes it.

00:06:15 Depends on your perspective, right.

00:06:17 So that left me with the other thing I was very good in early, was arithmetic.

00:06:24 And then when I got into high school, I took geometry.

00:06:30 And the man who taught it was head of the math department.

00:06:33 And he realized that I was very good in it and sort of made me monitor, gave me special

00:06:39 things to do.

00:06:41 And then I was going to be a mathematician.

00:06:42 And that only lasted for a year, because I then had a high school chemistry teacher

00:06:47 by the name of Morris Munzack.

00:06:49 And he made chemistry very exciting for me.

00:06:52 And so I was then going to be a chemist.

00:06:55 My senior year, I took physics and had a pretty awful physics teacher, so I won't say his

00:07:00 name, though I remember it very well.

00:07:04 And I learned so little physics that when I took the physics regents, I only got an

00:07:08 85.

00:07:10 And in order to get a regent scholarship, I had to do better than that.

00:07:15 And so I graduated high school in January of 37 and studied physics on my own and retook

00:07:25 the physics regents and got a 98.

00:07:29 So that I did get a regent scholarship, which was of course a big help in going to college.

00:07:39 This was the time of the Great Depression and everybody was very poor.

00:07:43 And so I had the opportunity to go to Hunter College, which was a city college and had

00:07:50 no tuition.

00:07:52 So that the $100 a year of the state regent scholarship plus tutoring helped pay my way

00:07:57 through school.

00:08:00 When I entered college, I thought I would be a chemistry teacher because of my high

00:08:06 school experiences with chemistry and physics.

00:08:09 The chemistry department at Hunter was quite large and I never had a feeling that the teachers

00:08:15 cared very much about you individually.

00:08:18 The physics department was quite small.

00:08:20 When I entered Hunter, there was no physics major.

00:08:25 There were physics minors for people who were either math majors or chemistry majors.

00:08:29 So I started out as a chemistry major and a physics minor.

00:08:33 The physics department took a good deal of interest in me.

00:08:38 There were three men teachers who probably would not have been at Hunter except it was

00:08:47 the Depression years.

00:08:50 Duane Roller was probably the best known of them all.

00:08:55 He had worked with Millikan.

00:08:57 In fact, they had written a textbook together, Millikan, Roller, and Watson, which was one

00:09:03 of the books from which we studied.

00:09:08 Then there was Herb Otis, who really had the most influence on me.

00:09:14 He gave me most of my physics courses and again, he made me sort of a teaching assistant

00:09:19 for him.

00:09:20 I worked up laboratory problems for them before they were given to the rest of the students.

00:09:28 He spent a lot of time with me.

00:09:30 And then there was Gerald Zacharias, who was one of Robbie's boys.

00:09:35 Robbie did not get the Nobel Prize until several years after that, but it was already known

00:09:41 that his work on magnetic resonance would lead to a Nobel Prize.

00:09:45 Zacharias, of course, was involved with war work and then spent the rest of his career

00:09:50 at MIT.

00:09:51 So I was just there at a very good time.

00:09:54 Serendipity, perhaps.

00:09:56 Well, I like to say I've always been in the right place at the right time.

00:10:04 My physics teachers, of course, encouraged me to go on to graduate work in physics.

00:10:10 On the other hand, at that time, there were relatively few women in physics.

00:10:14 In 1921, when I was born, two percent of the PhDs in physics were women.

00:10:19 In 1941, when I graduated college, it was still two percent PhDs in physics were women.

00:10:28 And although they encouraged me to go on to graduate school, they couldn't guarantee that

00:10:32 I would go on to graduate school.

00:10:35 And so as an upper senior in September of 1940, Gerald Zacharias, whose wife was working

00:10:44 at the College of Physicians of Surgeons, arranged for me to have a job as secretary

00:10:53 to Rudolf Schoenheimer, one of the early greats in the use of deuterium in biomedical investigation.

00:11:01 And so as an upper senior, I switched to a physics major.

00:11:06 I took nine credits of physics at Hunter and one at night at City University in order

00:11:14 to complete the major.

00:11:16 I was the first physics major to graduate from Hunter and at the same time worked part-time

00:11:22 as a secretary for Rudolf Schoenheimer.

00:11:25 I had many talents that made me a good secretary.

00:11:28 I had taken typing when I entered college.

00:11:31 I could do laboratory work, so I knew how to make slides.

00:11:37 And in addition, I could read German and read his Germanic script.

00:11:41 So all these things put together, I was a reasonably good secretary.

00:11:47 I had to agree that when I graduated, I would take stenography.

00:11:52 And so when I graduated in January of 1941, a junior Phi Beta Magna Cum Laude, I went

00:11:59 to secretarial school to take stenography.

00:12:02 Fortunately, that lasted all of three weeks because on February 15th, I learned that the

00:12:09 University of Illinois was offering me a graduate assistantship in physics.

00:12:14 And that was absolutely fantastic.

00:12:16 I tore up my stenography books.

00:12:18 Dr. Schoenheimer and I had a non-aggression pact.

00:12:22 I wasn't going to do stenography, but he kept me on as secretary because I had all these

00:12:26 other good talents.

00:12:27 Right, right.

00:12:28 Were there any such things as career paths back then as we know them today, or did you

00:12:34 envision your life, what did you envision your life's work as being when you were in

00:12:37 graduate school?

00:12:39 Well, you have to go back to my entering graduate school.

00:12:43 I entered graduate school in September of 1941.

00:12:48 When I arrived at the University of Illinois, I appreciated, first of all, I was the only

00:12:53 woman in the 400 of the Faculty of Engineering.

00:12:58 I was 400 of the Faculty of Engineering.

00:13:02 Graduate assistants were considered faculty, but junior faculty.

00:13:05 I was the first woman they had taken into the physics department since 1917.

00:13:10 Now everybody knows what 17 and 41 had in common, the draft.

00:13:17 When I entered the physics department, I was sent to teach pre-med physics because

00:13:25 everybody knew that women couldn't teach engineering physics.

00:13:28 Oh, of course not.

00:13:31 During the three and a half years I spent at the University of Illinois, they appreciated

00:13:36 I did have talents as a teacher.

00:13:39 And as a result, the last six months, in September 1944, I was the only graduate assistant

00:13:49 who was given an instructorship so that while I was finishing my PhD thesis, I was teaching

00:13:55 15 hours a week.

00:13:57 15 hours?

00:13:58 15 hours a week.

00:13:59 These were the war years.

00:14:00 The department was very much reduced.

00:14:03 We had the ASTP, the people from the Army who returned to the universities for engineering

00:14:09 studies.

00:14:10 We had the Navy group that was returned, and they had very few people who could teach physics.

00:14:17 And so they suddenly learned that women could teach 15 hours of engineering physics and

00:14:23 be considered about the best in the class.

00:14:25 Well this woman could anyway.

00:14:28 It sounds as though you've had a great deal of influence from your teachers as those who

00:14:33 got you interested in teaching, as well as interested in a career that was not typical

00:14:38 of women in those days, or in fact is not typical today.

00:14:42 Well actually at the University of Illinois, there were many people who were prejudiced

00:14:45 against women, including the acting head of department.

00:14:49 It turned out that Dr. Payton, for whom I was teaching pre-med physics, recognized my

00:14:55 talents as a teacher, and I had the good fortune to have as my research director Dr. Maurice

00:15:02 Goldhaber, whose wife, Trudy Goldhaber, was a distinguished physicist in her own right,

00:15:09 but who could not have a job because of nepotism rules.

00:15:14 But what did she do?

00:15:16 She worked in the laboratory, free.

00:15:19 It wasn't until after the war that they offered her a modest position at the University of

00:15:25 Illinois, but she and Maurice went on to Brookhaven, where he eventually headed Brookhaven National

00:15:31 Laboratories.

00:15:34 But the fact that it was a husband-wife team that really were my research directors made

00:15:40 it very much easier.

00:15:43 They were very accepting of having a woman.

00:15:45 But going to take a degree in physics during the war years was not easy.

00:15:51 Most of our teachers had left after the first year.

00:15:55 Fortunately, most of my theoretical courses were taken during the first year, so it was

00:15:59 laboratory work from then on out.

00:16:02 But I remember distinctly hiding the last hundred microamp meter because Los Alamos

00:16:10 raided our lab and took out almost anything that was movable.

00:16:16 The laboratories were kind of skippy those days because of the war.

00:16:19 They certainly were.

00:16:20 The University of Illinois people were very much involved in the Manhattan Project.

00:16:27 Oppenheimer headed it, and our theoretical physics department were all Oppie's boys,

00:16:33 and so they were taken away very early in the game.

00:16:37 When did you first meet Aaron Yalow?

00:16:38 Was it around this part of your life?

00:16:41 Aaron and I entered graduate school at the same time, and I met him the first day.

00:16:45 Was it love at first sight?

00:16:46 I can say it was really love at first sight.

00:16:54 We did have a laboratory course together, and one night I transferred, when he wasn't

00:16:59 around, 2,000 pounds of lead bricks.

00:17:01 2,000 pounds?

00:17:02 One ton?

00:17:03 That's right.

00:17:04 That probably made me most unique in his eyes.

00:17:09 I thought the way a man's heart was through his stomach.

00:17:15 That's what we were taught.

00:17:16 Well, actually, again, there were nepotism rules.

00:17:22 Although we had decided to get married, we couldn't until one of us was no longer a graduate

00:17:28 assistant, and Aaron took a fellowship, and I stayed on as a graduate assistant, and therefore

00:17:34 that permitted us to be married.

00:17:40 When we set up a very interesting household, we had a private house that must have been

00:17:45 converted from a garage.

00:17:48 In those days, living was very safe, and this was in Champaign-Urbana, and in Champaign-Urbana,

00:17:55 you couldn't get good things like pumpernickel or things that are now sold all over the country,

00:18:01 and my husband was a rabbi's son, and therefore we kept a kosher house, and kosher food, again,

00:18:07 had to come in from Chicago.

00:18:09 And so we had a lovely little house where we kept a window open, and where our friends

00:18:14 would go to Chicago, would come in and deposit food in our house or eat food in our house.

00:18:20 It was a very casual way of life in those days.

00:18:24 It sounds as though it was fun as well as hard work.

00:18:29 It was hard work.

00:18:31 I had a very heavy teaching program.

00:18:34 I was married in June of 43, and I still had almost two more years to go, and so I had

00:18:43 a heavy teaching program.

00:18:45 I was managing a house, and in addition, a thesis work in physics is not easy.

00:18:51 I can imagine that.

00:18:53 How did you become interested in medical physics?

00:18:56 Well, we're going to have to find out what happened to me before then.

00:19:01 Okay, all right.

00:19:02 I graduated in January of 45.

00:19:06 The war was still on, and as a result, I took a job for IT&T Research Laboratories.

00:19:14 It was then called Federal Telecommunications.

00:19:16 It's actually a very interesting laboratory.

00:19:20 The main laboratory for IT&T had been in Paris, and as the Germans came in, they evacuated

00:19:29 all of their Jewish engineers to the States.

00:19:33 It was their Jewish engineers who set up this research laboratory.

00:19:38 So it was a very new laboratory when I came in, and I went into what was a very exciting

00:19:45 division of that laboratory.

00:19:47 We were going to be sort of the theoretical, the designers for the laboratory.

00:19:52 Our laboratory was headed by J.B.H. Cooper, who went to Brookhaven at the end of the war,

00:19:59 and it was a nice laboratory.

00:20:02 There were only PhDs in physics in it, and I learned to design instrumentation things

00:20:07 that in extension of what I had done in graduate school, because certainly in those days, you

00:20:12 built your own instruments.

00:20:13 You did your own glassblowing.

00:20:17 When the war ended, this very nice laboratory I was in started to break up.

00:20:22 J.B.H.

00:20:23 Cooper went to Brookhaven, and the laboratory sort of, that group disintegrated, and so

00:20:30 I had been teaching nights at Hunter College while I was working for IT&T, and then I decided

00:20:39 I'd give up working in the commercial laboratory and go back to my alma mater, Hunter, to teach.

00:20:45 In September of 46, Hunter initiated a two-year engineering program for returning veterans

00:20:54 who would then be fed into City College at the end of those first two years.

00:20:58 So my first experience was teaching in this pre-engineering program, and that was a very

00:21:10 interesting group.

00:21:11 Four or five of the boys have gone on to become vice presidents for research in various major

00:21:16 companies.

00:21:17 Every now and then when I show up in a strange town, I get a phone call.

00:21:22 If there's been publicity, could they take me out to dinner?

00:21:25 So I've stayed on occasional contact with some of them.

00:21:31 And my husband, who had been teaching, decided that he would take a job in medical physics

00:21:39 up at Montefiore Hospital in the Bronx.

00:21:43 And my first exposure to medical physics was very interesting.

00:21:47 This was before radioisotopes were available from Oak Ridge.

00:21:51 And Sam Seidlin, the endocrinologist, thyroidologist, received his radioactive iodine for the treatment

00:21:59 of thyroid cancer from the MIT cyclotron.

00:22:03 It cost $1,800, and it was mostly the 12-hour iodine-130.

00:22:10 Now iodine's removed from the body with a halftime of about nine hours, and only a very

00:22:16 small fraction of it was taken up in the tumor.

00:22:19 So in order not to waste that $1,800 dose of radioactive iodine, every time the patient

00:22:26 voided, I received the urine to extract the iodine and give it to him.

00:22:32 So this was my first introduction to medical physics.

00:22:38 Actually my husband left medical physics after that and went to teach at Cooper Union, where

00:22:42 he has retired recently as professor of physics.

00:22:48 But it excited my interest, and through my husband I met Edith Quimby, who was one of

00:22:56 the leading medical physicists in the country.

00:23:00 In fact, one of my introductions was reading her book on the physical foundations of radiology,

00:23:09 together with the other greats in medical physics at the time, Glasser, Quimby, Taylor,

00:23:13 and Weatherwax.

00:23:15 And so I went to visit Dr. Quimby at her laboratory and volunteered to work in her lab over the

00:23:26 summer so that I could learn the methodology of application of radioisotopes in clinical

00:23:32 medicine.

00:23:33 And she spoke to me for about 10, 15 minutes and said, have to take you in to see the chief.

00:23:40 And the chief was Failla, who was the country's leading medical physicist.

00:23:47 And Failla spoke to me for about 15 minutes, talking about what I knew in nuclear physics,

00:23:53 instrumentation, things like that.

00:23:55 And he said, have to make a phone call.

00:23:57 Well, Failla was very important and I was just sort of a junior.

00:24:01 And okay.

00:24:03 So I hear him make a phone call in which he says, Bernie, I have somebody with me.

00:24:11 If you want to get radioisotopes, you have to hire her.

00:24:13 I later learned the story is Failla was chief consultant in radiology, radiotherapy at the

00:24:19 Bronx Veterans Administration Hospital.

00:24:23 Bernie Roswit was head of radiotherapy.

00:24:26 He had been planning on setting up a radioisotope program with an x-ray technician as the technician.

00:24:33 Failla realized that this was never going to work and had prevented their getting radioisotopes

00:24:38 until Bernie had to hire me.

00:24:42 Hey, that's great.

00:24:43 It didn't take them long to recognize your talents.

00:24:46 At any rate, this was during the summer.

00:24:48 It wasn't until December of 47 that they actually finished all the paperwork.

00:24:55 And so December of 47, I went to work at the Veterans Administration Hospital as a consultant

00:25:00 to set up a radioisotope program, at the same time keeping my job at Hunter.

00:25:06 This was Hunter in the Bronx, what is now known as Lehman College.

00:25:10 So they were only about a mile apart.

00:25:13 And it was therefore relatively easy for me to go back and forth between the two places.

00:25:20 By this time, I was already teaching women because this pre-engineering program only

00:25:26 lasted for two years, two, three years.

00:25:29 So I was already teaching women and I had discovered a very bright student in my class

00:25:39 who I thought should be a physicist.

00:25:42 When I decided in January of 1950 to go to the VA full-time, because research meant a

00:25:50 good deal to me by that time, I stayed on one extra semester to teach one course, nuclear

00:25:58 physics, to one of the women I had discovered.

00:26:03 And my reward came many years later when I read in this book published by the New York

00:26:11 Academy of Sciences about a conference they had had on successful women in the sciences

00:26:18 and analysis of determinants.

00:26:21 And I read just a little phrase that I love to read and even now reread.

00:26:27 My professional career can be said to have started with freshman physics.

00:26:33 My performance in that class impressed my teacher enough so that she, on her own, started

00:26:38 to offer me professional counseling.

00:26:40 She suggested a career in science would be more suitable than elementary school teaching.

00:26:46 This professor maintained an interest in me throughout my undergraduate days at Hunter

00:26:49 College and broadened my horizons by many orders of magnitude.

00:26:54 That was my student, Mildred Dresselhaus, and I take great pride in the fact that she

00:26:59 was elected to the National Academy of Engineering before I was elected to the National Academy

00:27:04 of Sciences and last year was elected to the National Academy of Sciences.

00:27:10 She's Abby Rockefeller Professor of Electrical Engineering at MIT and has had a very distinguished

00:27:16 career in science as well as having four children.

00:27:19 Good for her and good for you for getting her interested in this field.

00:27:22 So that, you know, I've enjoyed teaching and I was always sorry to have to give up teaching.

00:27:31 But I really could not maintain both a total commitment to what the work at the VA required

00:27:38 and the ability to be as good a teacher as I would have wanted to be.

00:27:44 Now when I came in to set up a radioisotope program, this was in the radiotherapy department,

00:27:52 and I think in these early days most people were thinking of reactor-produced or cyclotron-produced

00:27:59 radioisotopes for the treatment of cancer.

00:28:02 This is logically why we went into radiotherapy department.

00:28:08 However, in 1948 I read a book that changed my life.

00:28:12 The book is called Radioactive Indicators and it was written by George de Hevesy who

00:28:22 received the Nobel Prize in Chemistry in 1943 for the application of isotopic methodology

00:28:30 in chemistry.

00:28:31 In this book he described the application of radioisotopes in biochemistry, animal physiology,

00:28:39 and pathology.

00:28:41 Described also the sort of restricted uses that it had in medicine up to that period

00:28:46 of time.

00:28:47 And he predicted in this book that it would be the last book of its kind.

00:28:51 He said from now on radioisotopes will be so commonly used that they will be just described

00:28:58 as part of other texts.

00:29:01 And he's right, there's never been another book like this.

00:29:04 But when I read this book I realized that radiotherapy was a very limited use of radioisotopes

00:29:11 in medicine and that what we really needed was somebody trained in internal medicine

00:29:17 to share the program with me.

00:29:19 You have to remember that I was trained in college in chemistry, in graduate school in

00:29:25 physics, never had a course in biology in my life.

00:29:28 Never, never had a course in biology in my life.

00:29:32 And therefore I appreciated I needed on-the-job training in biology and medicine and it seemed

00:29:40 obvious to me that an internist would be the way to go.

00:29:44 The first two years from essentially 48, 49 into early 50, I served as general physicist

00:29:55 in the radiotherapy, radiology department.

00:29:58 I was involved in treatment planning.

00:30:01 I was involved in health and protection.

00:30:05 One of my first papers was a nomogram that would permit physicians to determine the dose

00:30:11 in air at the skin of patients receiving radiologic examinations.

00:30:17 At that time, too, we had World War II veterans who had had very severe facial injuries that

00:30:25 required facial reconstruction.

00:30:28 We developed a technique then that would enable us to tell the surgeon when the two

00:30:34 pedicle grafts had their circulation well enough restored that they could be safely

00:30:40 lifted from the chest.

00:30:42 So we did a variety of interesting things with different people in the hospital, but

00:30:49 I still appreciated that I needed more than that and I went to the chief of medicine and

00:30:57 said that we would hire anyone who he felt would work out well, that would establish

00:31:04 good relationships between us and medicine.

00:31:08 And he told me, I have a resident, brightest resident I've ever had.

00:31:12 He has a job at another VA hospital, but if you can convince him to join you, I think

00:31:18 it would be good for you and be good for him.

00:31:21 And so in April of 1950, Saul Berson came down.

00:31:24 I thought to be interviewed.

00:31:26 He came down with a group of math puzzles, all of which I solved.

00:31:32 And so I passed the interview, you passed the interview, and he joined our service in

00:31:39 July of 1950.

00:31:44 We worked together very well and after he'd been in about a year or two, he said, he asked

00:31:50 if I would give up working with the other physicians and in characteristic fashion said,

00:31:56 stick with me, I'll have your name up in lights.

00:32:00 And that was the beginning of the team of Berson and Gallo.

00:32:03 That was really the beginning of the team.

00:32:04 I did give up the other physicians in the hospital I was working with and we became

00:32:11 the team.

00:32:14 There's another interesting story attached to that.

00:32:18 In 1954, another VA hospital opened, the 23rd Street VA.

00:32:25 Another one in New York.

00:32:26 Another one in New York.

00:32:28 And Saul Berson was going to be offered the chief of the radioisotope service down there.

00:32:35 And the senior people at our hospital were quite willing to let him go.

00:32:41 And I complained and eventually they told me that if he went there, I'd find somebody

00:32:52 else and keep their program going.

00:32:55 I said, nothing doing.

00:32:56 I'd go down to the 23rd Street VA, I wasn't going to do this all over again.

00:33:01 And I gave birth to my daughter in September of 1954 and actually had to speak in Washington

00:33:12 eight days after she was born.

00:33:15 And I went into VA's central office and discussed this with him while you were in Washington.

00:33:21 While I was in Washington.

00:33:23 And it was agreed that Saul Berson would become head of the radioisotope unit at the Bronx

00:33:28 VA and he and I would stay there rather than transferring to the 23rd Street VA.

00:33:34 And as it turned out, a year or two later when they did set up the radioisotope program

00:33:39 at the 23rd Street VA, one of our professional children became its chief.

00:33:44 Very good.

00:33:45 Very good.

00:33:46 How did you and Saul work as a scientific team?

00:33:49 Did you meet every week or every day or how was it structured?

00:33:55 It wasn't every week or every day.

00:33:57 Our desks sat opposite each other.

00:34:01 In fact, in the old building when we moved upstairs, we had an office that was so small

00:34:07 that we had two tiny single pedestal desks facing each other.

00:34:12 And if you ask how our mind, first of all, I learned medicine from him.

00:34:15 I mean, I can't say he learned math and physics from me because he just left that up to you.

00:34:21 No, that's not true.

00:34:23 Saul loved to study physics and math.

00:34:26 I think he wanted to be a physicist mathematician and I wanted to be a physician.

00:34:30 So it exchanged very well.

00:34:36 And I like to tell the story that not long before he died in 72, we were playing a six

00:34:43 letter word game where you had a sort of guess what the other was thinking.

00:34:51 And of all the words in the English language, we both had the same word.

00:34:55 Really?

00:34:56 What was that word?

00:34:57 I forgot.

00:35:00 But it was just that way.

00:35:04 You never could tell who was thinking what because we were talking to each other constantly.

00:35:10 On the same wavelength all the time.

00:35:11 On the same wavelength.

00:35:15 Well tell us a little bit about how you discovered radio immunoassay, which is what you were

00:35:20 awarded the Nobel Prize for.

00:35:22 Well I think I ought to tell you what Saul and I were working on and how it developed.

00:35:28 Like everybody else when he came in, we first started work on thyroid disease because radio

00:35:34 iodine use in thyroid disease was a very important thing.

00:35:39 The buzz procedure of the...

00:35:40 Yeah, while everybody else was doing 24 hour uptakes, we developed a technique called thyroid

00:35:45 iodine clearance where we measured the rate of removal of radio iodine by the thyroid

00:35:51 and by the kidneys.

00:35:52 And so we developed a 30 minute test instead of the 24 hour uptake test that was generally

00:35:58 used.

00:35:59 Then we made use...

00:36:00 How did that work?

00:36:01 How did that test work?

00:36:02 Oh, essentially what you did is you gave an intravenous dose of radioactive iodine and

00:36:08 you measured the rate of uptake during the first 30 minutes.

00:36:11 We then, by sampling blood from 10 or 20 patients, we determined the average base of distribution

00:36:19 of radio iodine during that period of time.

00:36:22 So from the average base of distribution and the amount taken up by the thyroid and the

00:36:26 amount cleared in the urine in that half hour period, we could determine the rate of removal

00:36:31 by the thyroid, the rate of removal by the kidneys, and this was knowing the plasma concentrations,

00:36:38 we then could determine the clearance.

00:36:41 Now in 1940, Hevesy had already described the use of P32 labeled red cells for blood

00:36:49 volume determinations.

00:36:52 And we introduced the use of potassium 42 labeled red cells for blood volume determinations.

00:36:59 And we, like a number of other people, started to work with labeled serum albumin for blood

00:37:04 volume determinations.

00:37:07 And we discovered, as one might have anticipated but nobody else had published, that the space

00:37:13 of distribution of red cells was different from the space of distribution of labeled

00:37:17 albumin, essentially because there are small capillaries, too small for the red cells to

00:37:23 go through, through which you could get plasma.

00:37:27 So that we define the average body hematocrit things of this type.

00:37:33 Studying with the labeled albumin, we realized that it left the bloodstream and that you

00:37:39 would find the degradation product radioiodin in the urine after you had blocked the thyroid.

00:37:45 And so we thought we could introduce methodology then for studying the distribution and turnover

00:37:50 of labeled albumin.

00:37:53 Actually Ken Sterling had been doing similar studies at the same time.

00:37:59 His turnover for labeled albumin was of the order of 10 days, whereas biosynthetically

00:38:05 labeled albumin, the turnovers were thought to be very much longer than that.

00:38:12 And so we developed a methodology for demonstrating that the high specific activity albumin that

00:38:19 was being supplied commercially at that time resulted in the I-131 beta particles damaging

00:38:26 the labeled albumin and being responsible for shorter turnover time.

00:38:33 And so we did considerable work in demonstrating that you would have to make a lower specific

00:38:40 activity albumin if you wanted to have the longer turnover time.

00:38:44 And we did the studies with I-131 damage and also with x-ray damage.

00:38:52 So that we had had considerable experience with the problems of using iodine labeled

00:38:58 material and its use in studying the distribution and turnover of serum proteins.

00:39:04 We did studies in which we used, in which we studied the turnover of I-131 labeled globin.

00:39:12 Globin was a 35,000 molecular weight peptide that had been suggested for use as a plasma

00:39:16 expander.

00:39:18 And so we thought we would determine how the body handles it and whether or not it's effective

00:39:22 as a plasma expander and it turns out it wasn't.

00:39:25 So this was our background when in 1952 Arthur Murski, a distinguished diabetologist, suggested

00:39:32 that diabetes in the adult might be due to abnormal degradation of insulin.

00:39:40 Now why did he make this suggestion?

00:39:42 He made this suggestion for several very good reasons.

00:39:45 One is it was already known from the work of Renshaw in 1952 that the pancreas of most

00:39:52 adult diabetics, unlike what was then called the juvenile diabetics, contained adequate

00:39:58 amounts of insulin.

00:39:59 Some had half as much insulin, but some pancreas even had more insulin in the diabetic than

00:40:06 the non-diabetic.

00:40:09 In addition to this, Arthur Murski had described that the liver, the kidney, and other tissues

00:40:15 were capable of degrading insulin.

00:40:17 He investigated the kinetics of an insulin-degrading enzyme that he called insulinase.

00:40:23 And then 30 years ago everybody thought all diabetes was associated with an absolute deficiency

00:40:28 of insulin because all diabetics were treated with insulin before the days of the oral hypoglycemic

00:40:34 agents, the pills that lower blood sugar.

00:40:36 So if you consider the pancreas has enough, everybody thinks there's insufficient insulin

00:40:42 in the circulation.

00:40:43 And you describe an enzyme that can destroy it, obviously diabetes was due to the body

00:40:50 destroying insulin too rapidly.

00:40:52 Well, Saul and I had had these techniques going for studying the distribution and turnover

00:40:56 of serum protein, no reason not to extend it to study the distribution and turnover

00:41:01 of labeled insulin.

00:41:02 If the Murski hypothesis were right, then insulin would disappear more quickly from

00:41:07 the plasma of the diabetic following intravenous administration.

00:41:12 To our surprise, the labeled insulin disappeared much more slowly.

00:41:18 Now there are other things.

00:41:20 In our hospital at that time, they were still using insulin shock therapy.

00:41:25 And we gave labeled insulin to one of these patients and discovered that it disappeared

00:41:29 more slowly from their plasma.

00:41:31 From a non-diabetic?

00:41:32 From a non-diabetic who had a previous history of insulin therapy.

00:41:37 In addition to which, we had a patient known as M.N., who when he first came to our laboratory

00:41:43 shortly after his diabetes was discovered was a rapid disappearer.

00:41:47 And after four months of insulin therapy, he was converted to a slow disappearer.

00:41:52 So we recognized that the difference between the slow disappearers and the rapid disappearers

00:41:57 was not diabetes per se, but a previous history of insulin therapy.

00:42:03 Interestingly enough, one of the leading diabetologists in the country made the same

00:42:07 observation at the same time.

00:42:09 And he concluded that the reason for the slow disappearance is that the diabetic could not

00:42:16 handle insulin appropriately.

00:42:18 He didn't have that non-diabetic that we had.

00:42:22 Later when I saw one of his young associates, I said, you see, we have the same data, but

00:42:27 we looked at it differently.

00:42:29 That's why I ended up with a Nobel Prize.

00:42:32 Now when we attributed the delayed rate of disappearance to the binding of 6,000 molecular

00:42:39 weight insulin to a big molecule like gamma globulin, which would then retard its disappearance

00:42:44 from the capillaries, this was not well accepted.

00:42:48 Because in the 1950s, everybody knew that peptides smaller than 10,000 molecular weight

00:42:53 could not be antigenic.

00:42:55 Insulin was only 6,000 molecular weight, therefore, ipso facto, it was not antigenic.

00:43:00 Everybody knew that.

00:43:01 So the paper was turned down by Nature and was submitted to the Journal of Clinical Investigation.

00:43:10 It was rejected.

00:43:11 We revised it.

00:43:12 It was rejected again.

00:43:14 I saved that famous letter of rejection and published it as part of my Nobel speech.

00:43:20 Essentially the letter of rejection indicated that yes, we had demonstrated that labeled

00:43:25 insulin was bound to a protein that had the characteristics of a gamma globulin.

00:43:33 But everybody knows insulin is not antigenic, and therefore, we could not call it an antibody.

00:43:39 And so we compromised.

00:43:40 Saul was already on the editorial board of the Journal of Clinical Investigation for

00:43:44 our work in diabetes, blood volume determinations.

00:43:46 He was already a member of the society.

00:43:49 And so we compromised.

00:43:52 We changed the title from insulin-transporting antibody to insulin-binding globulin.

00:43:58 And at the bottom of that article, we had a little paragraph that now seems rather stupid

00:44:04 in which we said, maybe you won't let us call it an antibody, but it has all the characteristics

00:44:10 of an antibody.

00:44:13 Now why had the discovery of insulin-binding antibodies been missed?

00:44:17 We thought it was because the concentration was so low, the classic immunologic techniques

00:44:21 would not permit its detection.

00:44:24 And so we introduced radioisotopic techniques that permitted us to determine the quantity

00:44:31 of insulin-binding antibody in the circulation.

00:44:33 It turns out that most insulin-treated diabetics, even those treated with the dirty old insulins

00:44:39 of those of 30 years ago, had an insulin-binding capacity of less than one unit of insulin

00:44:45 per liter of plasma.

00:44:48 So it could bind only a few units of insulin, which was small compared to the typical dosage.

00:44:52 And this is why it was being missed.

00:44:54 We described a large group of patients with insulin resistance, which even in those days

00:45:00 was relatively uncommon, where the insulin resistance could be attributable to the higher

00:45:04 concentration of insulin-binding antibody.

00:45:07 Now the way in which we attempted to determine the concentration of insulin-binding antibody

00:45:13 was to keep a fixed amount of insulin, a fixed dilution of antiserum, and add increasing

00:45:19 concentrations of insulin to essentially saturate the antibody-binding sites.

00:45:27 And we soon appreciated that we could do the reverse.

00:45:33 Because if in place of the standards we substituted an unknown plasma, we could then tell its

00:45:40 concentration by comparing the binding of labeled antigen to antibody in the unknown

00:45:48 with that of standard.

00:45:50 So I can't say that we said Eureka.

00:45:53 I mean, as soon as we did it, we knew it.

00:45:57 Actually we used the word immunoassay in an abstract we sent to the Society for Clinical

00:46:03 Investigation for the 1957 meeting.

00:46:06 And that was rejected, wasn't accepted for presentation.

00:46:10 And actually science was more leisurely in those days.

00:46:14 So that although we had the principle in that original paper, we didn't have the practice

00:46:20 till 1959.

00:46:23 And the reason why we didn't have the practice was that for the most part, human insulin

00:46:29 reacted relatively poorly with the insulin antiserum that we had obtained from diabetic

00:46:35 patients.

00:46:37 And the antiserum had too low sensitivity for the detection of insulin.

00:46:46 And so we felt we would have to go to an animal to produce antibodies that would be appropriate.

00:46:53 As it turns out, insulin isn't very antigenic in rabbits because human and animal insulins

00:47:00 are very much like rabbit insulin.

00:47:02 We now know.

00:47:03 We didn't know it then.

00:47:04 And so we immunized both rabbits and guinea pigs and were able to demonstrate that the

00:47:09 guinea pig developed antiserum of high enough titer and good enough sensitivity to be able

00:47:17 to detect the levels of insulin in plasma.

00:47:21 And of course we now know why, because guinea pig insulin differs in 17 out of 51 sites

00:47:26 from the animal insulins.

00:47:28 Did someone in one of the articles written about you say something that the sensitivity

00:47:32 of radio immunoassay is like determining a cube of sugar in Lake Erie or something like

00:47:39 that?

00:47:40 Yeah, the Nobel Committee said that.

00:47:42 Since this is sort of designed for scientists, I'd like to point out that we can measure

00:47:48 concentrations as low as 10 to the minus 14th molar.

00:47:51 Fantastic.

00:47:52 Absolutely fantastic.

00:47:54 This had actually revolutionized clinical chemistry laboratory assays, I think.

00:48:00 Yes.

00:48:01 It's led to enzyme immunoassay and fluorometric immunoassay and therapeutic drug monitoring

00:48:08 and all the things that you could do.

00:48:10 Actually, I can say a few things about that.

00:48:13 Nowadays detail men are essentially selling enzyme-linked assays and fluorescent-linked

00:48:18 assays so that you don't have to have radioactivity in your laboratory.

00:48:22 This is one of the things that I don't like.

00:48:25 Actually, you'll find that these other techniques are used primarily for things, as you've mentioned,

00:48:30 such as drug monitoring or other situations where the concentration is very high.

00:48:36 You have to appreciate that the radio immunoassay was initially designed for measurement of

00:48:42 the peptide hormones, and actually insulin is one of the peptide hormones in highest

00:48:46 concentration in the blood.

00:48:49 Other peptide hormones, such as, say, cholecystokinin or secretin, are present at the picogram per

00:48:59 milliliter.

00:49:01 They haven't designed enzyme assays to go to that sensitivity.

00:49:07 Absolutely right.

00:49:10 One of the things that we talked about, you mentioned just a minute ago, okay, all right.

00:49:20 Stretch a little, huh?