ASH Oral History: Louis Diamond
ASH provides the following oral history for historical purposes. The opinions expressed by the interviewees are not necessarily those of ASH, nor does ASH endorse or make claim as to the accuracy of any of the information included here. This oral history also is not intended as medical advice; you should always seek advice from a qualified health provider for your individual medical needs.
The following oral history memoir is the result of two tape-recorded interviews with Dr. Louis K. Diamond, conducted by Eric Hoffman on November 17 and November 18, 1986, in San Francisco, California. Dr. Diamond has reviewed the transcript and made corrections and emendations. In 2008, Dr. Diamond's daughter, Susan J. Diamond, reviewed the transcript and made additional minor corrections. The reader is asked to bear in mind that the following oral history is a verbatim transcript of spoken, rather than written, prose.
Q: Dr. Diamond, I have you as being born in New York City in 1902. I was wondering if you could supply some early biographical data--about your childhood, early education, and etcetera.
Diamond: No, I was born in Russia in 1902 and immigrated with my parents at age two to live on the lower east side of New York City. My father was a storekeeper. We remained there through the first five or six years of my life. I attended the New York public schools, starting there. Then as we moved around New York City, leaving the lower east side for the upper Manhattan, the area which is now Harlem, I continued in New York public schools. Various different areas. Because of the desire to live in a better neighborhood, we moved up to what was then, and now, known as Washington Heights, where I continued school from about my ninth year of age through graduation at about thirteen.
Q: Where did your family come from originally?
Diamond: Originally from what is now Russia -- the Ukraine area? Crimea, I guess. The Black Sea area. They, of course, ran away at the time of the pogroms there, and came across Europe and eventually sailed out of Hamburg, or one of the German ports, to New York City where they had relatives, and therefore settled there. Both my father's and my mother's families were fairly large, were settled in the New York area. They remain there. I attended this public school at Washington Heights, which I still remember because it was a very good school. We were very well taught there. In fact when I finished there sometime around my twelve-and-a-half or thirteenth year, I could easily enter Townsend Harris Hall, which is a branch really of City College of New York. Most of the graduates of Townsend Harris Hall go to City College. Townsend Harris Hall was a three year high school, but a very classical one. You had to take Latin, math, learn English well. The education was concentrated. They cover in three years what the ordinary high school takes four years to do.
Q: Was there any special training in the sciences at that time?
Diamond: Not that I can recall. It was a general program. I don't remember that any one subject interested me more than any other. I went on from there to City College for a year because most of the colleges to which I wanted to go demanded a four year high school course. So I had one year at a combination of Townsend Harris Hall and City College of New York.
Q: Did you during that one year at City College specialize in any area or take a particular interest in any area?
Diamond: No. Again, it was a general sort of course. My aim was to accumulate enough credits so that I could enter some other college, preferably out of town. Go away from home. I did in fact get to Harvard College. Entered in the class of 1923 at Harvard College.
Q: What were your impressions of Harvard coming in as class of 1923?
Diamond: Well this was 1919, 1920. I was thrilled at being able to go there, and immediately took as many courses as I could. I think I had five full courses instead of the usual four. But I didn't have any particular bent. At that time we didn't need to pick a field of concentration until our sophomore year at least. Sometimes you could delay even longer. I tended to aim toward science, even in my freshman year at Harvard. Became more and more interested in chemistry. We had a marvelous teacher in inorganic chemistry, under whose influence I rapidly became interested in this as my field of concentration. He happened to be James Bryant Conant, who eventually of course was the President of Harvard. Conant was the sort of lecturer who never used notes. He'd just stand up there and say, "Now in the last talk, here I ended at this." He could go on smoothly and make it very exciting. So I had one-and-a-half courses with Conant. Came to know him personally, too. I've forgotten what discussion led to his remembering me by name, because I used that later to my advantage. Being interested in chemistry I took as many courses as I could. I had to of course diversify a bit. One of the exciting courses -- and this would interest you--was with a man named James Lawrence Henderson. He had a reddish peak beard, and he talked in a high-pitched voice. But like Conant he could talk endlessly without notes. He was actually called the "Pink Jesus," because with his beard he looked somewhat clerical. He had just come back from a sabbatical in France. One of his pet subjects was food, how beautifully the French could prepare food which we butchered over here. But whatever he talked on, he made it interesting. The course in the history of science, which is what he taught, was fascinating. He also, as you probably know, was a great biochemist. He actually set up the bio-chemistry study of human fluids.
Q: Were you aware of the attempts to establish a biochemistry department at Harvard during that period?
Diamond: No. Not until afterward did I really get in to that. But with his exciting portrayal of the history of science, and particularly the biochemistry of human fluids. He was the first to show that human salts and human circulation were really a carry-over from our life in the ocean. So Lawrence Henderson is really a model scientist for everyone.
Q: Did you participate in any of his seminars on the history of science?
Diamond: No. I never got that far. At that time his first year back from sabbatical he took very few students and gave very few courses. Just the history of science, biochemistry, and so on. But under really his stimulation I became more and more interested in medicine, and medical aspects of chemistry. But not to the point where I was certain that I wanted to go to medical school. I was going to take a graduate course in chemistry. That's where I became more closely interested in Conant's courses, because I was going to take a course with him to get a master's degree in inorganic chemistry. But I never did get to that, because by my senior year in college I was pretty sure that I wanted to go into medicine. Also that if I went in to medicine I'd want to deal with children. The reason for that was that I supported myself to a great extent, in college and medical school. In college I earned money during the summer as a camp counselor dealing with children, and was very happy in that sort of work. In addition to that I did get a partial scholarship so that I could get through there. Also I had a part-time job at the Varsity Club. I was not an athlete, but I was a friend of a fair number of athletes including the student director of the training table at the Varsity Club. He was a great athlete -- he was a miler, and a half-miler. He won both in the Yale-Harvard meets, for example. We became quite friendly. We were in a course in chemistry laboratory together, and I helped him quite a bit. In return he helped me get a job at the Varsity Club which gave me privilege at eating my meals with the athletes at the varsity training table as long as I joined some squad. Of all things with my 145-pound weight I didn't qualify for anything like football, but I went out for the scrubs football team. Just being a member of the scrubs entitled me to eat at the training table.
So that helped pay my way through college also. In the summer I was a camp counselor, for three summers. That paid pretty well. But I was certain with that past experience that first, I wanted to go in to medicine; and second, that I liked dealing with children. That's what eventually turned out.
Q: Were there any particular problems--medical or scientific--that interested you in terms of pediatrics at that time? Were these questions that were discussed?
Diamond: No. Just the fact that I liked dealing with children; I seemed to be able to handle them fairly well as a camp counselor. In fact I -- well, we'll get to that. I became a camp doctor summers after I entered medical school. Even after my first year in medical school I was signed up as a "doctor" at a camp. All I could do was pick out these sick children and get a real doctor to see them. Otherwise I took care of cuts and bruises. But I applied to Harvard Medical School when I graduated from Harvard College in 1923, and was very fortunate, I felt, in being accepted there. Because although I had fairly good grades, had scholarship grades at the college in my senior year particularly, there were only 150 places at the medical school. I think they had over six, seven hundred applicants. Many of them were veterans who had just returned from the War, which ended of course in 1919.
Q: What sort of criteria were used at that time to choose medical applicants? Were you made aware of the needs to fulfill certain course requirements, or service requirements?
Diamond: Yes. Very definite course requirements in the sciences, and some spread to other areas. But I had a good letter -- oh! I forgot to tell you in my senior year in college, when I was thinking of getting a further degree in chemistry. After I was due to graduate college in 1923 I received an offer to act as a tutor and then an instructor in chemistry at some small college down south -- I've even forgotten the name of it. But that was due to Conant's giving me a strong recommendation, of course. He also gave me a strong letter of recommendation when I eventually told him I wanted to go to medical school. Now I think it was that, and also I got a letter of recommendation from Henderson, that got me in to medical school despite the large number of applicants.
Q: What was the attitude of first Conant and then Henderson toward undergraduates who seemed to be interested in chemistry then deciding on a career in medicine? Would they encourage that?
Diamond: Very much so. They both felt that medicine, medical students and doctors, needed more chemistry, more biochemistry particularly than they had been exposed to in colleges. So that they applauded, or backed, my wanting to go to medical school, and gave me strong letters of recommendation -- I guess, because I did get in without too much trouble.
Q: Do you think they almost saw you playing a vanguard role, and spreading the gospel of chemistry amongst medical profession?
Diamond: I can't say. They were very kind to other pre-medical students too. Lawrence Henderson was just fine in that respect. He did want the gospel of biochemistry to be part of the medical background of the students, and kept up his interest in biochemistry for medical students.
Q: Did you come in to contact during that time with some of the other chemist, for example [Otto] Folin?
Diamond: When I got to medical school.
Q: If you could remember at a later time that could be interesting. Because there's research going on now on the role that the relationship between biochemistry and the medical schools played in the development of the discipline of bio-chemistry itself. So it's interesting to know who the various characters are.
Diamond: I think another person that influenced me during medical school was the great Hans Zinsser, he was professor of bacteriology and head of the department at the medical school. I came over twice to listen with medical student friends of mine to listen to Zinsser teach. I know his son, as a matter of fact. When I was in Children's Hospital in pediatrics I was once called to see his son, who was known as W. Bradford Cannon to distinguish him from his father. He's still alive, still at Harvard. When I saw Brad as a consultant for some acute infection, I became friendly with Walter R.Cannon.
Q: Upon entering Harvard Medical School, did you notice any differences in terms of the type of education you were asked to under-go?
Diamond: No. It was a standard medical school curriculum. It's completely changed, or very much changed, now. There was practically no contact with clinical medicine in the first year, excepting for a few clinics given by outstanding teachers to stimulate the students. Like two lectures at the Peter Bent Brigham Hospital by Harvey Cushing, the great brain surgeon. I helped take care of some children that he operated on. We didn't have a children's neuro-surgeon at that time, so we when we had children with neuro-surgical problems we'd send them over to the Brigham for Harvey Cushing or one of his assistants to work on. I had one very interesting, difficult case -- neuritis -- that he operated on three times. I was in charge of medical care, so I came to know him quite well.
Q: Were the courses mainly of a theoretical bent during the first part of your undergraduate training?
Diamond: A regular course in anatomy, and bacteriology, and then biochemistry and physiology, through the first year and in the second year, when pathology and bacteriology were the basic courses. You didn't get in to any clinical contacts, except for the occasional clinic, until the latter part of the second year, when you took what they called "physical diagnosis"-- learning how to do a physical examination, listen to the heart and lungs, and palpate the abdomen and so on. That was usually given in the outpatient department at the Brigham Hospital or at the Children's or City Hospitals. We were assigned to different hospitals.
Q: Were you aware at that time of the various attempts to reform the medical school curriculum of people such as David Edsall?
Diamond: Yes. He was a great Dean, of course. Helped build up the school, and change the courses. I don't know whether there was resistance from the pre-clinical faculty to try keep the students in their own specialty rather than let them go toward clinical medicine. But we were not encouraged to do anything like that until the third year. Then, of course, we had to take clinical courses. In fact at that time we had to learn to handle obstetric problems and deliver twelve babies ourselves "on the district," so called, meaning outside the hospital in the homes. Usually the students would deliver six in their third year, and the second six either in the summer between the third and fourth year or in the fourth year, when you'd have a two-week stint of obstetrics and go to the homes of patients that were enrolled in the clinic to be delivered in the homes by medical students with the support of the resident in obstetrics when you needed help.
Q: Would you recall roughly what the proportion of home deliveries to hospital deliveries was at that period?
Diamond: Well, we'd have four students on at a time. No, I don't recall. But there were a small number of hospital deliveries. Most of them were home deliveries, enrolled through the lying-in Hospital outpatient department. Delivered by students or residents, and usually only brought in to the hospital if there was any problem.
Q: Is there anything more that you'd like to say about David Edsall? Apparently his view of the need for what he called "bedside research" did meet with some resistance from some of the older guard.
Diamond: I guess so. He, of course, was a disciple of Osler's. He wanted very much to have the students learn clinical medicine at the bedside of patients. By the time I got there he was full-time Dean and didn't give any ward rounds himself. But, he arranged special courses, elective courses, of which there were three or four -- and I took a few -- with great teachers like Francis Peabody and George Minot. Henry Christian met with them at Brigham Hospital. Howard Means at the Massachusetts General Hospital. I think Edsall very much favored contact with clinical medicine. I got to know -- both his sons went to medical school. John Edsall, and Jeffrey. Jeffrey is dead now. He was the younger son, and John was a classmate of mine at medical school. He never practiced medicine.
Q: He developed fairly early on an interest in protein chemistry.
Diamond: Oh yes. He went to England for a year, studied chemistry there and then came back to Harvard College as professor of biochemistry. He had an MD degree, but he's never used it.
Q: Could you say something more about Francis Peabody?
Diamond: He was a great bedside clinician. I did not get to see much of him. He developed cancer of the stomach and died in my senior year, or shortly after that. But I attended a few ward rounds with him. He emphasized the importance of patient care. He wrote a little book on the care of the patient. It's a classic. No more than about fifty pages. He wrote several papers on the bone marrow in pernicious anemia. He was one of George Minot's teachers and associates. He influenced George Minot to study pernicious anemia. But his own articles, his own research, were on the bone marrow changes in pernicious anemia. He recognized it as being a bone marrow disease, and not an infectious disease, which some people at that time believed. He was a tremendous teacher.
He set up what was called the Fourth Medical Service at the Boston City Hospital. The first belonged to Boston University; the second and fourth to Harvard. Francis Peabody was the physician-in-chief on the Fourth Medical Service, which was the outstanding one.
Q: Could you say something further about Henry Christian?
Diamond: He was the Chief at the Peter Rent Brigham Hospital. I did not have any contact with him. He was not only a great teacher, but the author of a fine textbook of medicine.
Q: This would be General Textbook in Internal Medicine?
Q: Howard Means was the other name that you mentioned.
Diamond: He was the Chief of Medicine at the Massachusetts General Hospital. I didn't have any contact with him. His interest was thyroid disease.
Q: You mentioned George Minot a number of times.
Diamond: I'll get to him in a moment, because I had a fellowship with him.
Q: Right. Were there any other personalities that you would like to mention, from your medical school period?
Diamond: Yes, in my third year, outside of the medical school in Cambridge, New York. It was close to the border of Vermont. Kenneth Blackfan was the son and grandson of the doctors who took care of patients in Cambridge -- he was the town doctor. Kenneth Blackfan, therefore, naturally entered medicine and went to Albany Medical School. When he finished there, and after a year's internship at Albany Hospital, he returned to practice medicine in the town of in medical school I had a pediatric course, standard pediatrics. The Chief of Pediatrics was a young man who had an interesting background. His name was Kenneth D. Blackfan. He came from a small town in upper New York, not far from Glens Falls, -- Cambridge, taking over his father's practice But, he was interested in doing more than just general practice, and came under the influence of a pathologist named Pearson, who was professor of pathology and bacteriology in Philadelphia -- the University of Pennsylvania. He summered in a little town in Vermont--I think it's called Dorset, Vermont--on the New York-Vermont border. He told Blackfan that he ought to go in to some specialty because Blackfan wasn't too happy with just taking care of all sorts of problems such as his father had taken care of. Because Blackfan enjoyed taking care of children, Pearson persuaded Blackfan to go in to pediatrics. He became the physician to a Foundling Home in Philadelphia, an orphanage where he, Blackfan, had charge of a hundred children. In his year there he made contact with pediatricians who used to come to the Home to take care of the children. They thought he did a remarkable job. When he was due to finish there, he was offered a residency in Philadelphia. The chief there was a prominent pediatrician named Howland. This must have been about 1912, 1913. Howland developed a very fine service with special interest in biochemistry as applied to medicine. Washington University of St. Louis under Edsall's stimulus -- Edsall, incidentally, had come from Pennsylvania. Been professor and dean at Pennsylvania --
Q: This is David Edsall.
Diamond: David -- before he went to Harvard as first, professor at Harvard and then, dean. The Brigham Hospital was just opening then -- newly built, and Harvard Medical School was newly built, around 1913. At any rate Howland was invited, they reorganized the Washington University Medical School in St. Louis. Got a lot of money I think, I don't know -- Rockefeller and other places. They invited Howland to set up the pediatric department at Washington in St. Louis.
Q: With an emphasis on biochemistry? He had a particular interest in biochemistry?
Diamond: Yes. In the feeding of children, and the digestion of children. He was a good pediatrician. In fact he and Emmett Holt wrote the first textbook. Holt wrote the first textbook of pediatrics, and Howland helped him write the second edition. Holt and Howland's textbook became the standard textbook. At any rate, Howland went to St. Louis as Chief of Pediatrics up at Children's Hospital, and at the Medical School. Washington University still ranks as one of the outstanding schools. Howland invited Blackfan to come to Saint Louis as resident at the Children's Hospital. Howland was there only two years, and then Johns Hopkins opened a new pediatric division called the Harriet Lane Home. When Howland transferred to Johns Hopkins as the professor of pediatrics and the head of the Harriet Lane Home, he persuaded Blackfan to come as his resident. At that time, or shortly after Blackfan got there in 1914, the war broke out. Everybody went off to the war. Blackfan wanted to go but he had a facial palsy, and therefore was excused, couldn't go. But Howland went, set up a hospital overseas, and left Blackfan in charge of Harriet Lane Home. So Blackfan as senior resident of pediatrics remained as resident for seven years, but actually ran the Harriet Lane Home and taught pediatrics to many medical students. When Howland came back, Blackfan of course was immediately upped to Associate Professor. Then shortly after that, interestingly, the school of medicine in Cincinnati -- Cincinnati University Medical School -- There was a pediatrician named Griffitts, I think -- as Chief of Pediatrics.
Q: Could you continue with your discussion on Blackfan, please?
Diamond: Dr. Griffitts, the pediatrician, at Cincinnati -- Professor of Pediatrics at the Cincinnati Medical School--had under his care the children of a businessman named Proctor, in Cincinnati. He was the Proctor of Proctor and Gamble. To show his gratitude to Griffitts, Proctor said he'd give him money to set up some research at the children's hospital. He not only gave his own money, he gave stock in his company, Proctor and Gamble. It was interesting that the Children's Hospital directors, businessmen, said "This is valuable stock. Sell it! We need the money." Griffitts said, "Don't sell Proctor and Gamble stock. It'll be worth more later on." He persuaded them to hold on to Proctor and Gamble stock. In fact, Proctor gave Griffitt more stocks -- or the family gave them to him. Eventually, they had quite a bit of stock. Anyway, the Children's Hospital Research Foundation, in Cincinnati, turned out to be one of the wealthiest and the best research units in pediatrics.
Q: What sort of research was carried out?
Diamond: Everything: They had research in biochemistry, pathology. I know some of the men that went there were good biochemists, hematologists, nutritionists. The Cincinnati Children's Hospital Research Foundation is still one of the larger well-endowed and active research foundations in pediatrics.
Q: About when was the research foundation actually established?
Diamond: I can't tell you the exact year, but it must have been some time around 1919, 1920, the early 1920's.
Q: Would this have been one of the first places where there was a real push to have experimental science linked to--
Diamond: I think it was one of the first. That and Hopkins. And Pennsylvania had had some. Saint Louis, of course, when they got the new medical school. Cincinnati was looking for a Chief of Pediatrics. But when Cincinnati wanted a full-time Chief of Pediatrics, which they hadn't had, they asked Howland who to get, and he pushed Blackfan. Blackfan went there, 1921, as Chief of Pediatrics at Cincinnati Children's Hospital. Then when Edsall was Dean at Harvard, they had had only a part-time Chief of Pediatrics, at Harvard in the Children's Hospital, an old-timer named John Leavitt Morse. M-O-R-S-E. Famous pediatrician in Boston. Edsall wanted a full-time chief, and they invited Schloss -- Oscar Schloss from New York, who was professor of pediatrics at Cornell -- to come to Harvard as the first full-time professor at pediatrics at Harvard. Schloss was a very fine experimentalist with an interest in allergy. He'd really established allergy as a specialty.
Q: Did he work with Coca?
Diamond: I don't know. They had a relationship in New York anyway. Schloss was a wonderful teacher. Schloss came to Boston and made the mistake of bringing his staff with him. Not a whole staff--he brought four or five men with him. And put them in as heads of various subdivisions at the Children's Hospital. Demanded, I guess, and got the resignation of 3 of the men who had been at the Children's, who were practitioners. They had no full-time staff. You can imagine what that did to the pediatricians in Boston, which was a center of pediatric practice under Morse. Incidentally, it was two separate hospitals. The Infant's Hospital and the Children's Hospital. Different directorships, although some joint staff. Of course John Leavitt Morse, who had retired or was out as head, never forgave Schloss for bringing his own men. Schloss had had a big, wealthy practice in New York. He had been hoping, and had been told, that he'd get a large consultation practice in Boston. But John Leavitt Morse and his men who were put out made sure that they didn't get any consultation practice to speak of. So this promise of a consultation practice, which Schloss needed because full-time professors got very little salary then, just didn't materialize when he got to Boston.
Q: Could you recall the names of some of the families that--
Diamond: Not me. They would. I'm sure they would remember him. He just had a big consultation, and family practice. That's where most of his income came from. I think a full-time professor at Cornell, as at Harvard, probably got in the neighborhood of eight or ten thousand dollars at the most. So Schloss, bringing his own men, and doing a good job at the Children's, reorganized everything, made it much more of a scientific place, could not stand more than two years at this. Then he was offered a better position to return to Cornell, went back to Cornell.
Q: When you say that it was made much more of a scientific place, can you be more specific about--
Diamond: Well, he set up research in biochemistry, in nutrition. He set up research in bacteriology, taking care of infectious diseases. He organized a very good outpatient department, which hadn't been quite as well thought out before him. He brought his own men to run the outpatient department. They forced the resignation of the practitioners of pediatrics in Boston. They couldn't even admit patients at Children's Hospital without going through a resident. You can imagine how they took that. At any rate, Schloss left Boston. Dean Edsall invited Blackfan to come as Chief of Pediatrics at Harvard, and head of Pediatrics at the Children's Hospital. Blackfan was a small man, only about five foot three. Very quiet, a diplomat, an excellent physician, and a good diagnostician. Took good care of the children. When he came to Boston, he only brought two or three men with him, and re-appointed, I understand--I can't vouch for this--some of the old practitioners in Boston to bring their patients in. In the next couple of years, he rebuilt the Children's Hospital reputation. Fit it in well with the practitioners. He, himself, was asked out as a consultant. That was permissible at the Harvard system -- even the full-time men are allowed to have consultation practices. Blackfan rebuilt the Children's outpatient department clinical service. Had good, young men coming as interns. Made it a graduate appointment only. You couldn't get an appointment as a resident at the Children's and Infant's Hospital--they were combined -- until you'd had at least one year general medicine or its equivalent. Got outstanding men. As I say, he brought with him two or three good men. One of them was a doctor named McKhann. Dr. McKhann's still alive. He came as Dr. Blackfan's assistant from Cincinnati, where he had been a resident. He also brought with him George Guest. G-U-E-S-T. Now dead. But put him in charge of bacteriology and infectious disease.
Q: What was McKhann's role in this? What did McKhann do?
Diamond: McKhann was Blackfan's assistant. He was associate, assistant professor and associate. I bring him in because he was a strong influence on me. I'll bring that up. So Blackfan established this very good service. Was a very good teacher, a slow, careful speaker, and an excellent clinician. He taught clinical medicine the way Osler did. Just talking to the patient, quizzing the patient, making the patient feel that he was being cared for. Dr. Blackfan gave a few lectures at the end of the second year of medical school, to medical students, on how to examine the infant and child, and some other feeding problems and clinical problems in pediatrics. I think he gave a series of six clinics, maybe more. They were fascinating. That, too, made me feel sure pediatrics was my specialty. During the summer after my second year, I had to deliver babies, of course. I delivered them at the New York Lying-In Hospital down on the east side--Second Avenue and Fifteenth Street. Boy, was that a breeding ground.
Q: Could you describe it some?
Diamond: PJ, it dealt with poor patients. It was an old hospital. They took patients from all over the east side. They also did some research on anesthesia as I remember. They had an outpatient service where they delivered many patients in their homes. That's where in the summer after my third year, I went and went out on district and delivered patients -- delivered my six. We had to have 12 deliveries. Anyway, during that summer, also, I made contact with a very well-known pediatric specialist in New York, who was professor of clinical pediatrics at the Baby's Hospital of Columbia University P&S. His name was Fred Bartlett. He was one of the leading pediatricians, a wonderful clinician. Loved by everybody. A gentle person. Fred Bartlett was just -- there was a new hospital on upper Fifth Avenue called the Fifth Avenue Hospital. Right beyond Mount Sinai. I think it was therefore about 105th Street and Fifth Avenue. It's still there--it's New York Medical College.
Q: Right. That's where the New York Medical Library is.
Diamond: That's right. Anyway, that hospital had just been built, and he was asked to take over the pediatric service at that hospital. Toward the end of the summer when I was through delivering really, the middle of August--
Q: Which summer was this?
Diamond: This was the summer after my second year, so that was the summer of 1925. Fred Bartlett said, "Look. You're interested in pediatrics. Why don't you come down and help me at this new clinic I just opened up?" I said "Fine," and I went down there. I spent the next four or five weeks working at the clinic with him every day. Every morning and some of the afternoon. Apparently I satisfied him. He praised my work. When I went hack to Harvard in the third year we had a regular course in pediatrics, given by Dr. Blackfan, working in the outpatient department. Fred Bartlett was a friend of Blackfan's. He wrote a letter telling Blackfan that I had worked with him, and he thought I'd done a very good job. He hoped to persuade me to go in to pediatrics. So, when I took the course the third year at Harvard, I went up and told Dr. Blackfan, "Bartlett sends his regards." He said, "Yes," he had a letter from Bartlett telling him what a good job I had done. He therefore knew me better than some of the other third year students. Toward the end of my third year at Harvard I volunteered as a student research man in pediatrics, to work in a laboratory and work with Dr. McKhann, who was then studying the biochemistry of nutrition and had a laboratory in the Children's Hospital, a little research building there.
Q: If I could ask a question at this point. The number of times you've referred to the close connection between biochemistry and nutritional studies. That type of connection is not always that apparent today.
Diamond: The reason for the close connection was that when Blackfan came to Harvard from Cincinnati he had had with him in Baltimore a Professor James L. Gamble. Gamble was a biochemist. He had graduated Harvard, took an internship at the Mass. General. Was one of those quiet, hard working fellows who had always been interested in biochemistry. He had been at Hopkins, in the Harriet Lane Home, doing biochemistry and nutrition. Particularly body fluids -- sodium, potassium, fluoride, so on. He really stabilized that whole area in pediatrics, countrywide. Blackfan invited Gamble to come up and do his research at the Children's and Harvard Medical School. Gamble came and had laboratories set up in the laboratory research building. His laboratory was right next to where Dr. McKhann was set up--that's how I got to know Gamble very well. He was one of the Proctor and Gambles.
Q: So Proctor and Gamble enter into this story a number of different times.
Diamond: Right. Dr. James L. Gamble was at Harvard, then, as Professor of pediatrics and biochemistry at the Children's. I worked with Dr. McKhann two afternoons a week, and weekends. I did Kjeldahl, the basic routine for analyzing urine and so on -- the protein constituents.
Q: How do you spell that?
Diamond: Oh! I was afraid you'd ask! [laughs] Leave it out. Just say biochemistry of urines. It's Swedish.
At any rate, I spent a fair amount of time with Dr. McKhann. Dr. McKhann had been trained by Dr. Blackfan in Cincinnati, and then at Harvard. He was without doubt the keenest clinician I have ever known, next to Dr. Blackfan in some respects he was even greater than Dr. Blackfan as a diagnostician and caretaker. That's how I got to know Dr. McKhann. So, Dr. McKhann influenced me a great deal as a great clinician. He taught clinical medicine in pediatrics. He made some real contributions. He was the first one to develop gamma globulin as useful in measles and hepatitis -- prevent or modify measles and hepatitis.
Q: When was this worked on?
Diamond: Oh, his measles work was back in the 1930s, 1940s. The hepatitis was in the 1940s, when it began to he recognized. I think it's hepatitis B, the kind that you get from food. But McKhann developed gamma globulin which had been synthesized and purified by E. J. [Edwin] Cohn, a great biochemist.
Q: Did you make contact with Edwin Cohn during this period?
Diamond: Very much, I'll tell you more about that. I worked under him.
Q: Before we go on, do you think that we could generalize about the relationship between biochemistry and nutrition, or is this a specific interlapping area of interest for people such as Gamble? There are other people who are starting to push for a discipline of biochemistry who also came out of a nutritional background.
Diamond: Oh sure. That became, of course, the hot subject for research in infant feeding. I can't recall all the names that were so important, there. But there were a whole series of investigators who influenced the choice of formula, helped make up formula that are now part of routine artificial feeding for children both in Canada -- Toronto, Canada -- and Montreal. Toronto mostly, because that was where Connaught laboratories had a lot of research going on. Part of the University of Toronto. That's where they developed insulin, of course. But I can't recall all the pioneers in infant feeding that were in Boston, New York, Hopkins, and Marriott in Saint Louis. He followed Dr. Howland.
Q: How do you spell Marriott?
Diamond: M-A-R-R-I-O-T-T. He was a great influence in infant feeding.
Q: Would you have any notions about why at certain times there is greater interest in questions such as the biochemistry of infant feeding, and other times the interest recedes?
Diamond: Infant feeding became so important when it was recognized that a high percentage of the mortality of infants occurred in the first eighteen months, or the first year of life from bad feeding, contaminated food. In fact the Children's Hospital, even before Blackfan's day, recognized that lack of sterility, lack of precautions against contamination, was the chief cause of high mortality. Particularly in the summertime, the hot weather, in Boston. Boston, through a group of ladies, had organized what they call a "floating hospital." They bought, or hired, a boat, and in hot weather they fitted it with beds and wards and doctors, pediatricians, and they would take infants out every day who were suffering from diarrheal disease, or who were from poor families, and take them out in to Boston Harbor -- that's why they called it a floating hospital. Where it was much cooler, and also where they could use better sterile precautions, and thereby saved a lot of lives. This went on, probably, for half a dozen summers. Hospital -- floating hospital. It was actually part of Tufts University.
Q: Do you know who was behind the program?
Diamond: One man at the time I was there was a Dr. Barron. B-A-R-R-O-N. But several pediatricians were involved in this. A floating hospital actually became--the ship burnt down a couple of times during the winter, and they had to get a new ship. They had a fair amount of money they collected and it became a branch of Tufts University and the Infants' Hospital at Tufts University. It was called the Floating Hospital, On-Shore Division. But infection, and summer diarrhea-cholera infantum--was the chief cause of mortality in big cities during the hot summertime. The pediatricians became interested, of course, in stabilizing formuli. There was a period when they had acidified milk.
Diamond: Acidophilous -- milk. Marriott out in Saint Louis was one of the backers of that, I believe, and some others in New York too. Isaac Abt from Chicago, was a famous pediatrician. He was interested in feeding children in Chicago. Real formuli were then developed. But Boston under Dr. John Morse had developed what they called percentage feeding. They take two percent butterfat -- cream -- and 40 percent water, and six percent sugar. They measured everything exactly. In fact, they'd make up formuli exactly for each child -- pediatricians who were in practice would make up percentage formuli. There was Walker Gordon Laboratories, a commercial organization -- milk company, that the pediatrician would call up and tell them to make up a formula of so much maltose, so much butterfat, so much water, so much salt particularly for the child.
Well Blackfan and Gamble very quickly showed that this was not necessary. That if you just took diluted milk and added some extra maltose, or even just ordinary sugar, you could make up a formuli that the children would do just as well and the mother could learn to do. Then of course they went in for canned, sterile, pasteurized, formuli -- sterilized formuli -- that they could just open the can and dilute it once and feed the child. Simplify feeding a great deal.
Q: Did Walker Gordon labs put up any resistance to the arguments of--
Diamond: No -- they were still busy enough. I don't know when they finally folded. They became part of the Hood Milk Company.
Q: The claim was that this was more scientific?
Diamond: Anyway, infant feeding was greatly influenced by Blackfan and Gamble, and other New York and Baltimore nutritionists. Down in Baltimore, a famous pediatrician Dr. Edwards Park. P-A-R-K. He had been trained by Howland. Blackfan, Powers, Park, and several other pediatricians were residents under Howland. They became chiefs of services.
Anyway, Gamble was of course the center light of biochemistry and of fluid therapy -- parental(?) therapy to treat children with diarrheal disease.
Q: Was there a very high mortality rate from the diarrheal disease?
Q: Until when did that continue, about, as a major problem?
Diamond: Until they learned to sterilize Torruli make them up fairly simply, and of course learn to protect children from the extreme heat of the Boston summers. For sick children we even had early on at the Children's and Infants Hospital some air-conditioned rooms. We were right next to the Harvard School of Public Health. There were some engineers there originally developed air conditioning.
Q: The air conditioning units were originally developed at the Harvard School?
Diamond: That was one place, yes, by men at the Harvard School of Public Health, and actually used at the Children's and Infants' Hospital. The first air-conditioned nurseries for premature babies were established at the Infants Hospital when I was there, under Dr. Blackfan around 1926,1927, 1928.
Q: The rationale for developing these units?
Diamond: Premature children have to be kept at a stable temperature. They couldn't go up and down the way full-term infants did. You couldn't keep them warm just by wrapping them in blankets. So we had two air-conditioned rooms. One of them at one temperature for infants, premies under three pounds, another one between three and four and a half pounds, and then they could go out on the ward. By that time they could stabilize their own temperature. But this was an important part of the reduction of morality of premature infants. Dr. Blackfan showed that you could reduce the mortality almost to the same as for ordinary full term infants by this air-conditioning and sterile precautions, and so on.
Q: There was an interest at that time in birth weight?
Diamond: Oh yes. We developed an air conditioned nursery at the Boston Lying-in. Children's Hospital pediatric department was in charge of the newborns at the Boston Lying-in across the street. That is true of other cities, too. They took over the care of premies. Dr. Blackfan wrote one of the first books on the care of premature babies. In terms of the actual research into the question of birth weight, that birth weight has something to do with survival rates. That was a question that was looked in to at that time and it'd be pasteurized and then used for infant feeding. That was quite an advance for the feeding of premature babies.
Q: Was there any biochemical interest, or interest by scientists in the biochemistry of breast milk during this period?
Diamond: Oh yes. I can't remember names of that, but again Dr. Gamble and his group, Dr. Marriott and his group I guess, Park and Powers -- all of these people. Powers, who was professor at Yale, was very much interested in infant feeding.
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Q: Dr. Diamond, would you care to elaborate on further experiences at Harvard, the Medical School, and perhaps talk about some of the other personalities that you came in to contact with?
Diamond: Yes. In my fourth year, as I began to plan to go into pediatrics, I wanted to intern at the Children's Hospital in Boston. Knowing that it was necessary to have a one year general medical appointment, I applied for medical internships for appointments after I graduated. Amongst them I had an application to the New York Hospital, which was the Cornell Medical teaching service. I was fortunate enough to be given an appointment there. But, in those days appointments to internships were usually staggered, like every three months, so that a new man came on and would be broken in by the man ahead of him. Therefore a one year appointment had one man starting July, next man October, third one February or January, and the fourth one in April. I received the appointment for April 1928. In other words, I'd have to wait awhile before I could start. I had approached Dr. Blackfan to put my name on the waiting list for an internship at the Children's after I finished the New York appointment, which would have been 1929. Dr. Blackfan said he would put me on the list, but of course he had dozens of applicants, and there was no certainty that I would make it. But in my fourth year as a medical student, I was on the Children's Hospital ward when we happened to have a few interesting hematologic cases -- blood diseases in children. Our consultant in hematology was Dr. George Minot. He came over to see the children with blood diseases. One of them was the second child in a family with big spleens and severe anemia. The cause of the anemia was obviously destruction of blood because the child was jaundiced. But it wasn't typical of what we call familial jaundice with anemia, or spherocytosis. Dr. Minot called this child an atypical hemolytic anemia, cause unknown. As a medical student I became interested enough to follow this case as well as others I'd had on the ward. In the fourth year we spent a month on the ward taking care of children, admitting them, working them up and so on with the interns in residence. Dr. Minot asked me to report to him about this child later on. That was my contact with Dr. Minot, who at that time had already begun working -- this is in 1926, 1927 -- with liver as a treatment for pernicious anemia. Recognized pernicious anemia as being a nutritional deficiency, and lacking in some important nutritional factor. So, reporting to him on this other child a few times, I went over to see him at the Huntington Memorial Hospital, a small hospital right next to Harvard Medical School on Huntington Avenue, endowed by the Huntington family. That's where Dr. Minot kept his pernicious anemia experimental patients. I did go over there, and got to see some of his patients, and made ward rounds with him. So, that was my contact with Dr. Minot. Also, as a fourth year medical student on the C.H. wards there was a three-year-old child admitted one night (when I was on service) with enlarged lymph glands, enlarged spleen, fever, and peculiar looking white blood. I worked him up. He'd been diagnosed as having Hodgkin disease on the basis of having a biopsy of the lymph gland done in his local hospital in Connecticut and had been sent to us as a case of infantile Hodgkin with a piece of the lymph gland. The professor of Pathology at H.M.S., and the head of pathology at the Children's, was Dr. Wolbach. He studied the lymph gland and said "it didn't look like Hodgkin disease. Maybe the child had something else." Dr. Blackfan came on ward rounds, and I was lucky. I'd taken the history, and I presented the case to him. I said "it had a peculiar blood, a peculiar lymph gland which was not typical of Hodgkin, that Dr. Wolbach thought it wasn't. We wondered whether it really was malignant Hodgkin disease in this little two-year-old," who looked pretty sick. Dr. Blackfan said, "I vaguely remember that there was an epidemic of fever and swollen lymph glands which they called "glandular fever," in a boy's school down near Johns Hopkins. It was described by the pathologist and the clinician, Drs. Sprunt and Evans. They also said there were peculiar cells in the blood. Maybe this child has glandular fever. Why don't you go look up what glandular fever is, get Sprunt and Evans' write-up."
Q: When did Sprunt and Evans do this work?
Diamond: It was done in 1926.
Q: It was quite current.
Diamond: Yes. It was very new -- maybe 1925, 1926. In fact, glandular fever was not known to most people. Excepting that there had been this epidemic. The gist of it was that I looked this up. Sure enough, the white cells were typical of what Sprunt and Evans had described. The fever and glands were typical. This is the first case of infectious mononucleosis recognized at the Children's Hospital. Dr. Blackfan was very pleased that he had made the diagnosis. This was February or March of 1927, before I graduated. Dr. Blackfan had me present this case to different groups, and special clinics. I became adept at presenting this case. Therefore, when I approached Dr. Blackfan after I got the appointment to New York hospital and told him I'd like to come to Children's, he said "Okay, we'll put you on the list." Well, toward May or June I was wondering what I'd do with the nine months I had to wait for my appointment. I asked Dr. Blackfan if I could work in the laboratory on blood conditions. He said, "I'm interested in blood conditions. I'd be glad to have you work on blood diseases in children, see what you can find." I worked up some good cases, including one case of the atypical hemolytic anemia which occurred in a little Greek boy. Dr. Blackfan, who always remembered. things, said "You know, Dr. Cooley in Detroit has collected four cases of hemolytic anemia and enlarged spleen in some Greek and Italian children. They're now calling it Cooley's anemia." He's called it von Jachsch, which is wrong. Von Jachsch was a German, and no German had Cooley's anemia. Cooley's anemia became established as a peculiar hereditary anemia in Greek and Italian children from around the Mediterranean region in particular. The great Dr. George Whipple named it thalassemia, meaning the sea --the Mediterranean Sea. Anyway, Dr. Cooley asked Dr. Blackfan if he could include our case of Cooley's anemia with his four and publish the first article of five cases of Cooley's anemia. Dr. Blackfan was very pleased with this. Although we contributed a case our name wasn't on it. But by that name we had four or five cases in the Children's Hospital -- Italian and Greek children. Dr. BlackFan said, "We ought to study these. Maybe you can study them while you're waiting for your appointment." Blackfan said, "I'll help you start a laboratory for the study of hematologic diseases in our Children's Hospital laboratory building, right next to Dr. McKhann and Dr. Gamble." Well, we had so many cases in short order that I couldn't tend to them all and continue medical school. We had so many peculiar blood conditions, too, and children with nutritional needs. Dr. Blackfan said, "If I get some money to establish a hematology laboratory, how would you like to take it on and give up your [blank] Instead spend a year here at New York Hospital studying in this blood laboratory. We'll count that your year internship and then you can have the appointment in pediatrics, guaranteed." Who could ask for anything more? So that's how I became a hematologist. There was no money. Dr. Blackfan got money just to buy a scope and to hire a technician. Then, he steered me to Dr. Wolbach and Dr. Minot. I became a research fellow under Dr. Minot, to make rounds with him and to take care of hemologic problems at the Children's Hospital. My appointment was actually in the Department of Pathology, and Dr. Wolbach gave me a fellowship there. That's how I became a pathologist too, for that one year while I set up the hematology laboratory.
Q: What were the sources of Dr. Wolbach's money? Would you know?
Diamond: He had fellowship funds. So that's how I established the hematology lab at the Children's. The following year I became assistant resident from October 1928, then senior assistant resident from 1929 to 1930. Then Blackfan offered me the chief residency, which was a three-year appointment. Dr. Blackfan had been chief resident of Hopkins for 12 years that was the Hopkins system.
Q: If we could return to this question of establishing a hematology laboratory. This would have been one of the first specifically designed laboratories for hematology?
Diamond: In children.
Q: For children.
Diamond: That's right. There wasn't, to my knowledge, such a laboratory in this country. There were abroad.
Q: So you had to decide on what sorts of equipment and what sorts of problems were to be worked on?
Diamond: No. We worked on all of the blood cases that came in -- outpatient, inpatient. Once we were established, Dr. Blackfan was able to get money. In fact, we got a grant from H.P. Hood Milk Company to run a hematology laboratory that took care of the expenses of a technician. They'd promised it for five years and equipment--microscopes, and so on.
Q: Why would the Hood Milk Company be interested in--
Diamond: They had a foundation that gave money for the benefit of children. They still have. They've been doing that now for well over, well, forty years. Because it was established in 1934 or something like that maybe 50 years.
Q: Would they maintain an archives that would be open for research?
Diamond: Oh they must.
Q: That would be interesting to look at.
Diamond: H.P. Hood Foundation. But that was the hematology lab. Also I began taking on a research fellow to assist me, and to train him in hematology, from about 1938, 1939.
Q: But hematology today is a very broad field. But back in the 1920s wasn't even self-defined as a field that might be some specialty.
Diamond: Yes it was. Wintrobe down at Baltimore, who then went out to Salt Lake City, Utah. Has written books.
Q: But his books didn't come for another -- his text wasn't until the 1940s.
Diamond: About then, yes.
Q: I mean in the 1920s, though, its not--
Diamond: Hematology was a recognized specialty with W.B. Castle -- certainly he was a recognized hematologist. Josephs down at Johns Hopkins was a pediatric hematologist. Carl Smith in New York at Cornell, who wrote a good textbook of pediatric hematology.
Q: When did that first come out? Do you recall?
Diamond: No I don't. It's in its fourth or fifth edition. That just so it was have come out -- oh, it was quite a bit after the war in the 1950s.
Q: How did you decide in terms of the equipment that was needed for a lab?
Diamond: Well in those days all we needed were microscopes, blood pipettes, and hemocytometers and glass slides.
Q: This raises an interesting question. It's one of the debates that I talked about earlier going on in the history of biology. Already at this time, Dr. Minot had approached the protein biochemist Edwin Cohn to use the latest research techniques in physical chemistry to try to figure out what this missing factor was in pernicious anemia.
Diamond: That's right. Dr. Cohn was a great protein chemist over at Harvard College. Cohn had suggested that he might purify the fraction of liver that contained the active principal. He was able to do that very quickly, then, of course it was taken over by the pharmaceutical industry. Then Cohn was invited to come to Harvard Medical School, and given laboratories there to continue pursuing his interest in the chemistry of proteins. This was during the War. The Navy asked him to do something about the difficulty of transporting bulk plasma for treatment of shock at the battlefront. He said, "Well, the active ingredient of plasma in treatments of shock was the albumin. I think I can purify and extract the albumin and thereby cut down the bulk from 500 cl to less than 100. In fact, to 25 ml." He proceeded to do that. As a by-product he synthesized purified gamma globulin, the antibody components of plasma.
Q: Dr. Diamond, I was wondering if you could comment on this possible transformation that's taking place among practitioners of hematology, the change from a basically morphological research style with microscope as your centerpiece of attention, to one that's to use up types of equipment of much greater analytic strength -- your centrifuges, etc. I was wondering if you could talk about whether you used the more sophisticated equipment in your lab, or you developed relationships with other labs that had this equipment?
Diamond: I had the advantage, as I indicated, of being in a small laboratory building of the Children's Hospital. It was a two-story building in the middle of the Children's Hospital complex -- the old Children's Hospital. This was devoted to research only -- research in bacteriology, in biochemistry, and in nutrition. Dr. Gamble did his studies on fluid balance in rats and rabbits, and carried over what was learned to the research on children. He had equipment of all sorts, and very soon we found that morphology of hematology did not help in analyzing all the hematological conditions that we encountered. In fact many of them, which were dependent on the size and shape of the red cell, its hemoglobin content, its fragility -- its membrane stability -- and measurements that one could not make by merely observing the cells under a microscope, although of course there was some hint of membrane defects when one saw odd-shaped red cells, odd-shaped white cells sometimes, and also variations in the size of the cells. Measurements of cell size was dependent on being able to measure the total volume of the red cell sediment, red cell centrifuge, and relate it to the hemoglobin, hemoglobin content, and so on.
With the equipment available in a well-established experimental laboratory, we had the advantage of being able to make such measurements. Early on, we started trying to study the red cell membrane. This became an important project in which we could get the help of the physicists as well as the biochemists that were in our own organization and around the medical school. Being right next door to the medical school gave us the advantage of being able to call on the experts there in various basic sciences.
Dr. Cohn, as I've all ready mentioned, transferred his protein laboratories from Harvard College in Cambridge to Harvard Medical School, and occupied one whole floor of a Medical School building, it was called the Laboratory in Physiologic Application of Hematology to Clinical Medicines -- some elaborate name of that sort. He very quickly built it up with skilled biochemists, protein chemists, and actually taught people that became leaders in the field in other parts of the country. Now his method of using combination of temperature and the control of the ionic environments -- the salt content -- and also alcohol as the precipitant of proteins, purifying proteins led to very rapid increase in the knowledge of the blood, of both the fluid portion -- plasma -- and the cellular portion.
Most of his efforts, of course, were in the fluid portion. He had isolated not only albumin and gamma globulin, but five fractions. Albumin was Fraction V. There was Fraction I, which was a clotting fraction; Fraction II also contained some clotting elements. He was able to purify these by his methods with very little adulteration. Some of them could then be tried clinically. For example, early on we used Fraction I, the fibrinogen faction, and a portion of it which contained anti-hemophilic clotting factor. The gamma globulin fraction contained some other globulins which had some endocrinologic value. So that this expanded the usefulness of blood a great number of times. In fact it used to him a standard joke that eventually they'd be able to use every portion of the blood plasma except the squeak that the patient usually let out when you put the needle in his arm. Dr. Cohn's vision was to be able to take a unit of blood from the individual, have this flow through a series of instruments, and have all the different fractions separated as it went through, and have them serve some great special purpose. During the war, albumin replaced plasma in some areas as the shock therapy of choice, particularly for the Navy where bulk was difficult to manage, and then the globulin fractions for use in various diseases where immunity was an important factor.
Q: Dr. Diamond, I was wondering if you could say some words about Dr. Nathan Rosenthal and some of the contacts which you had with him?
Diamond: Yes. Nathan Rosenthal was the leading hematologist of Mount Sinai Hospital, and had a large hematology consulting practice, most of whom had hematologic conditions that required blood transfusions. He was a very skillful transfusionist, and would pick up bottles -- bags of blood -- or arrange for the donor and the patient to be brought to a local hospital where he could take the blood and then infuse it very promptly by the indirect citrate method into recipients. He was a very skillful microscopist, too. So that if there were any questions about leukemia, for example, he could make diagnoses based on bone Warrow or blood examination at other people had missed.
The leading research laboratory for studying white blood cells in New York was up at Rockefeller Institute, where Dr. Florence Sabin, who had been at Johns Hopkins Hospital and Medical School for a long time as a research associate, had moved. She was the first woman, I believe, to be given the position of Associate -- which was like a full professorship -- at the Rockefeller Institute. She studied chiefly rabbits and pigeons, and studied the white blood cells about the time I first came to know her.
Having been at Hopkins, Dr. Blackfan, while he had been at Hopkins, had come to know her quite well. When she moved to the Rockefeller Institute he wrote her and asked if he could send one of his students down there to see how she studied living white blood cells with a technique she called the "super technique." This used a warm chamber -- a box, with a controlled temperature and a microscope inside the box. A slide with a drop of blood and stained with neutro red and janus green -- two vital stains which didn't kill the cells, but stained them, then one would follow the movements of the stained cells. Dr. Sabin showed a lot of interesting attributes of the living white blood cells, particularity the macrophages, the giant cells derived from monocytes that were so important in taking up and digesting foreign material like bacteria. The supravital technique became quite an achievement to study the growth of cells in pigeons, rabbits, and then to some extent in humans. Dr. Sabin usually had three or four Research Fellows who worked with her. They often became the leaders in hematology, like Dr. Charles Doan, who became professor of medicine at Ohio State and then Dean there. Dr. Claude Faulkner of New York, a medical school hematologist, and others. Dr. Blackfan arranged for me to work in Dr. Sabin's laboratory from June to September of 1927. There I learned her supravital technique, which I brought back to Boston Children's Hospital with me for our laboratory to study white cells in children.
One of Dr. Sabin's great contributions was the study of the activity of white cells in tuberculosis. She produced tuberculosis infection in rabbits and in guinea pigs, and then showed that the so-called giant epithelioid cells in the tuberculosis system that produced large collections of cells typical of tuberculosis in the lungs and elsewhere were macrocytes which had picked up the tubercule bacilli, and they in turn stimulated other cells, and eventually formed this large collection which is typical of tuberculosis. Her study of active tuberculosis in pigeons and then ours in humans, as well, was an advance in our knowledge of tuberculosis.
Dr. Blackfan and I published a paper in 1929, the first paper I published, on the diagnosis and the follow-up of the activity of the macrophage in active tuberculosis in childhood. This was the first project in our research laboratory in Boston.
Q: Could you expand on two points that you've raised now. One, could you talk a bit about the citrate method of indirect transfusion, and then if you could say some words on the status of leukemia research at the time that you made contact with Dr. Rosenthal.
Diamond: About leukemia research first, there was no such research going on then. When the diagnosis of leukemia was made on a patient it was a death warrant. There was no way of doing anything about it. Not until many years later, in fact in 1950, under the stimulus of some work done in Boston by Dr. Farber, the famous pathologist at Children's Hospital, and me, and the use of a new drug which a chemist, Dr. Suberow from the Lederle Company, developed. Now it is called methotrexate. That was the first drug -chemical --to be used in treatment of leukemia. Starting with its use in children with acute leukemia, we achieved first a 50 percent remission rate. Now it is one of the chief drugs not only for leukemia but for many other malignancies. Until that came along there was really no treatment for leukemia that was at all encouraging. All we could do was transfuse the patients and hope that some of them would go into partial remission.
Q: So the main types of studies, once again, were morphological studies.
Diamond: Exactly. Now, this brings up Rosenthal's method of indirect blood transfusion, in which he was the expert. Not infrequently leukemia patients would go into remission after receiving blood transfusions. Dr. Rosenthal did all the transfusions originally by the direct method, that is; connecting the vein of the donor to the vein of the recipient and by use of syringes just pumping from one in to the other. There was always the problem of clotting which could not be overcome in any simple way. The introduction of sodium citrate as a means of preventing clotting of blood, the so-called indirect transfusion method became popular. It was simple enough so that even a house officer could do it. Whereas formerly there were skilled transfusionists, like Dr. Rosenthal, who did direct transfusions, and who commanded good fees for doing that because it was a difficult technique to do without trouble.
Q: Did the use of sodium citrate lead to the replacement of these expert surgeons?
Diamond: Right. The direct transfusion method therefore fell into disuse. There was little advantage to it, and there was always the hazard that blood would clot in the syringe and would be lost, or that the catheter in the vein, or the needle in the vein, would clot and so on. So when citrate came in, transfusion became easy.
Q: There was a gap of time, wasn't there, between the period when Lewison first began to popularize the use of citrate and--
Diamond: Right. People didn't buy it too easily; they were afraid citrate was toxic, and if they didn't use the right amount of citrate they'd get reactions, and they could get reactions from poorly made up citrate and pyrogens in the fluid. As a matter of fact Rosenthal proved that most of the transfusion reactions that they ran in to, something like 10 percent reactions, were due to bacterial or other protein contaminants of the transfusion equipment or in the citrate solution, particularity if they used the same bottle and the same tubes over again and hadn't cleaned them thoroughly. Some protein material left would cause febrile reactions, and very serious ones, so that the indirect transfusion method, the citrate method, became popular and was generally used.
Q: How were the actual reactions overcome, if that was the problem with adapting the citrate method, and then was shown that there could be bacterial contamination?
Diamond: It was a matter of being sure of sterility of the equipment, thorough washing if you used equipment -- rubber tubes and bottles -- over and over again, which they usually did. Of course, they couldn't afford to throw away the bottles, and various people had their own type of bottle. In Boston we had what was called a Fenwal system devised by a Dr. Carl Walter (who's still alive), a surgeon who did very good transfusions. At any rate, the matter of cleaning the tubes and cleaning the bottles, avoiding contamination was what led to a very low percentage -- less than one percent -- transfusion reactions, in the hands of skilled people.
Q: Hospitals today have a central supply--
Diamond: Central supply labs and departments.
Q: They didn't exist at this time, or is this when they start to come in?
Diamond: No. Everybody supplied his own tubes and needles and bottles and equipment. We didn't trust a central supply room to do this. We felt it had to be done by somebody who would handle only transfusion equipment that was the usual way it was done.
Q: At then at a certain point central supply rooms became acceptable.
Diamond: Oh sure. Yes.
Q: When was this? Is there any particular --
Diamond: Oh, as far as transfusion equipment the central supply must have been popular in the late 1920s and early 1930s. But they took over blood transfusions when we began to have blood banks, and blood banks did not start much before the late 1930s. First there were plasma banks, where they discarded the red cells and just kept the plasma. They could freeze the plasma and reconstitute it afterwards. So plasma banks became popular at the beginning of the War.
Q: Where would the supply for sodium citrate and the other materials come from at that time?
Diamond: Chemical companies.
Q: So the big chemical companies expressed an interest in the new indirect transfusion method.
Diamond: Oh yes. Some of them made up solutions and bottled them. They could test for pyrogens, you see, and do a better job than each hospital.
Q: Do you remember some of the names of the original chemical companies that entered in to this field?
Diamond: I'm trying to remember the big one in New York. I'll think of it eventually. It's still in existence -- it's the big chemical supply house in New York. They supplied most of the citrate for transfusions.
During the early part of the War when plasma was the only thing that could be shipped distances, the American Red Cross began to collect plasma from volunteer donors in Red Cross stations, in New York, Baltimore, Boston and elsewhere, for use in England. They collected about thirteen million units of plasma, which they shipped overseas in dried form. Not until late in the War did we begin shipping whole blood. Of course they built their own blood banks in England and France and elsewhere.
Now, people were interested in something other than sodium citrate, to try to preserve blood longer than one week. We did have blood banks mostly in hospitals that -- I set up a blood bank at the Children's Hospital, and also the Boston Lying-in Hospital, in 1936, 1937.
Q: Those would be among the earliest blood banks?
Diamond: Some of the earliest.
Q: Also I've seen accounts that during the Spanish Civil War there were attempts to construct mobile blood banks.
Diamond: Yes. They did, but there they used really small amounts of blood. They only used the equivalent of about a half a pint, something like 250, 300 ml. But they did set it up, and it did work very well.
Now, at about that time a Dr. P. Mollison in England, working with a physiologist named Lautit, developed a new solution. It was based on the work of Rous at the Rockefeller Institute. He proved that red cells could be preserved in a dilute solution of citrate and glucose--dextrose--for experimental use (not for transfusion--they were using it in animals), for anywhere from two to four weeks.
Q: So this was a case of researchers at Rockefeller interested in completely different problem--
Diamond: Coming up with this.
Q: An idea that could be used for transfusions.
Diamond: Right. Whether Dr. Mollison and his associate, Dr. Lautit, picked this up or developed it themselves, they decided that they could preserve blood in citrate with dextrose, in proper dilution, so as not to hemolyze the cells, and they proved that blood could be preserved for three weeks at least. They started blood banks in England for this purpose.
Q: This was after the war had already begun?
Diamond: Yes. Toward the end of the war.
Q: So in a very real way it was the war itself that gave the impetus to the blood transfusion--
Diamond: Blood transfusion was some of the big advances that the War made in therapeutics. Until then transfusion wasn't as commonly used, except in anemia. Here it was used for all sorts of injuries, and
saved thousands of lives.
Q: Before we go further into the topic of blood banks and transfusions, I wonder if we could back step a little bit, and if you could perhaps draw some parallels or contrasts between the type of work that was done under Florence Sabin at Rockefeller, the type of labs that were set up for hematological work in Boston, and the work that Nathan Rosenthal's had envisioned at Mount Sinai. In other words if we could discuss, perhaps, different styles and approaches to establishing labs.
Diamond: Yes. Well, Nathan Rosenthal's ideas for blood labs never materialized, unfortunately. But Dr. Sabin had set up this very good research laboratory working with animals. Her pupils, like Charles Doan at Ohio State University Medical School set up a hematology research laboratory there -- he was a research man as well as a clinician. Dr. Claude Faulkner set up the same in New York City at Cornell Various people felt that hematology was a neglected area of research, and ought to be investigated more completely.
Q: Would Dr. Sabin's work fit into the new push to introduce new types of technology and techniques in hematology, or the older morphologic approaches?
Diamond: She was mostly a morphologist. Her background was of interest in that she had been a technician at Johns Hopkins. She decided to get a PhD in research, because she was a good research person, and did go ahead with that. Then from there she did such good work that she received an appointment at the Rockefeller Institute in New York City. Her laboratory was just as separate from clinical application as you could have. There were very few cross contacts.
Q: Was Charles Doan also a PhD?
Diamond: No, I don't think he ever took a PhD. But he spent a year or two with Florence Sabin. Then he became the leading hematologist in the mid-west, and set up his organization at Ohio State University
Q: Did Florence Sabin have any contacts with Karl Landsteiner?
Diamond: None at all. She kept clear -- she wanted nothing to do with clinical application in her work.
Q: The blood-typing was seen as clinical.
Diamond: Landsteiner 's work on human blood groups wasn't used by clinicians for years! Here he discovered this and published it in 1901. Of course, it was a short paper in German. The clinicians even in Germany ignored him. Over here they ignored him completely! So that didn't become common knowledge until the 1920s. Attempts to transfusion patients were purely random, often without any cognizance of the difference of blood groups and the relatively high reaction rates that resulted.
Now, blood banks began to be established particularly during and after the War. We in Boston established a blood bank at the Children's, at Peter Bent Brigham. There, Dr. Carl Walter, a surgeon, was the leading blood transfusionist, and he developed his own system--the "Fenwal System".
Q: Could you describe this Fenwal system?
Diamond: It was a matter of having bottles of a certain size, just enough for a unit of blood, and careful washing, careful tubing and glassware that was fitted to this. You had the whole set -- donor's set -- to take blood into. Then citrates -- the proper amount of citrate in there. Then in storage, and then use it with properly washed equipment, properly washed rubber tubing and so on. So, the Fenwal system eventually was taken over by the Fenwal Company in Chicago. It's one of the big companies that makes all sorts of equipment.
Anyway, we established this blood bank system in several hospitals in Boston. The Beth Israel, the Boston Lying-in, and the Children's Hospital. I also helped establish a blood bank system at the Massachusetts Memorial, which is part of Boston University Medical School. So, that's what I was busy with at that time.
Then Dr. E.J. Cohn, the brilliant protein chemist, foresaw that we would need a blood bank system in this country after the War. He persuaded the Red Cross to use the established plasma banks they had set up in 15 or 20 different cities to collect plasma, for the British and for ourselves, for the War, to consider making blood banks out of them after the War. They were loath to do that, because it meant spending a lot of money. However, Basil O'Connor became head of the American National Red Cross, and through his influence with Franklin Roosevelt, whose law partner he had been, Basil O'Connor said, "Yes. We will help you establish blood banks through the Red Cross." They needed somebody to set up the technical side of it. At that time, Roosevelt's personal physician had been Admiral Ross McIntyre, the Surgeon General of the Navy. He was appointed vice-president of the American Red Cross. He didn't personally have any skill with blood banks, but he had set up a plasma program for the navy when he was Surgeon General. So, he turned to Cohn, who was advisor to the plasma program.
Q: Did he personally know Cohn before this?
Diamond: Of course, since Dr. Cohn was the head of the albumin, plasma, and gamma globulin programs that the Red Cross had undertaken.
Q: Tullis had mentioned -- perhaps it took place at a later date -- that Cohn was good friends with General George Marshall, who later became head of the National Red Cross.
Diamond: Ross McIntyre was appointed a vice-president of the Red Cross and put in charge of blood plasma, albumin, and whole blood programs. He needed somebody to help him set up Red Cross blood banks. In February of 1951, Cohn called me and he said, "You're going down to advise Dr. McIntyre how to set up blood banks in all these Red Cross units. We're going to have a Red Cross blood transfusion --
Q: This was 1931, or 1951? Was this before the American entry in to the War?
Diamond: Oh no! This was long after.
Q: This was after the War! Okay.
Diamond: The Red Cross had closed all its plasma collection units following the war. This was in about 1948. So he said, "Would you go down to Washington and help Ross McIntyre set up blood banks and get the first one started? Rochester, New York has signified that they're willing to reopen their plasma unit and collect blood."
Q: Why would there be this interest in the part of Cohn, after the War, to continue the blood bank?
Diamond: Because he had rescued so many people with his albumin, and all these fractionation methods. He foresaw that they would be using all these fractions of blood for multiple purposes. For example, Fraction I, Fibrinigen V -- the clotting fraction, for bleeding difficulties, and so on.
Anyway, Dr. Cohn sent me down. I arrived in Washington and went in to Red Cross headquarters on 17th Street. I was greeted like someone red carpets rolled out, and people waiting, special "Yes Dr. Diamond,"--"No Dr. Diamond." Dr. McIntyre said, "You're going to open this first blood bank. It's already to open up in Rochester, New York. The Red Cross has agreed, and they have a fellow in charge there. We want to standardize it so we can have the second one ready to open in Washington D.C. and elsewhere." He said, "We've persuaded the Red Cross to open 36 transfusion units in the next three years." I said, "That's impossible. They'd have to build blood banks, proper equipment, proper rooms; volunteers and paid help to do the bleeding, get doctors." And, it was absolutely important not to step on doctors' toes, to get the local medical society to support it. That had been one in Rochester ahead of time. There were a lot of local medical societies, as we later learned, who wanted nothing to do with it because they thought it would take away from of the work of the doctors who were transfusionists. They wanted blood banks, maybe, but not under the Red Cross! Each hospital wanted to do its own collecting. Local groups formed blood transfusion services. New York had a big blood transfusion service outside of the Red Cross!
Q: Did they set themselves up in conflict with, or in competition with the Red Cross?
Diamond: They wouldn't let the Red Cross come in. We had to get permission, as I found out, local medical society first -- the Red Cross, that didn't want to try to try to get volunteers for this and all the local doctors.
Q: What was the rationale for going with the Red Cross over these local organizations?
Diamond: The Red Cross already had set-up plasma, that they had learned to use. Sure, they had closed up most of them. But for example, in Rochester New York they reopened their plasma unit, and they built a blood bank in downtown where it was easy. They supplied blood to several local hospitals, to save the hospital from opening up its own blood.
Q: So in terms of efficiency, in terms of quality control-
Diamond: In terms of getting donors the Red Cross knew how to get donors. They'd gotten it for plasma. They had the names of thousands of plasma donors.
Q: What would be the argument of the doctors who opposed the Red Cross, if it was shown that it would save hospitals money and would be more efficient in getting donors?
Diamond: They wanted control of their own blood banks. They feared the Red Cross would decide how much blood to collect, where to collect, and so on. There were a lot of possible conflicts, so we had to get an agreement of the local medical societies in each place, and the state medical societies. Anyway I started working with Dr. McIntyre -- I was to be there a week just to get the Red Cross Rochester bank going and then Washington D.C. But on the third day I came in and there was my name on the door, saying, Chief of Blood Transfusion Service or something like that. I said, "Look! I have a job back in Boston. I can't do this!" They said, "Just a minute -- Dr. Cohn wants you on the phone." Dr. Cohn said, "I've talked to the Dean. You are relieved of all pediatric responsibility. You're staying in Washington D.C. and organizing the Red Cross Transfusion Services."
Q: Cohn could do things just like that? How did you feel about it?
Diamond: I said, "Look, I've got a wife and two children, and a home. I've got a pediatric service and blood bank. I can't leave there." He said, "Well, the Dean said you're leaving." So there was no question. He said, "If you wish I'll talk to the President of the University," I said, "No, no!" But I didn't move to Washington. I commuted every week. I went down on a Sunday night, arrived there Monday morning, went to my office at the Red Cross, and stayed in a hotel all week long, and then went home for weekends. Occasionally I'd have to go on a trip to open up a new blood bank and so on.
We projected 36 blood banks in three or four years. Dr. McIntyre, and even General Marshall, said, "That may be too many. You can't organize that fast. That's too much trouble for the Red Cross." However, we opened 35 by the end of three years, so, but I did a fair amount of traveling. Wherever we opened one I'd have to go make sure everything was going all right. Ross McIntyre couldn't have been a sweeter person to work with -- just as nice as they make them.
Q: In terms of the actual developments in blood work, especially coming from Cohn's fractionation methods, perhaps you could comment a bit on what that did in terms of ties that were developed between universities and pharmaceutical companies and supply companies.
Diamond: Right. Cohn refused to patent the fractionation method for albumin, gamma globulin, and all the other fractions in his own name. He did patent it in terms of Harvard University, with the understanding of the manufacturers. He told the manufacturers how to do this. That they would not pay a royalty but would send the material that they extracted from the blood to a control testing laboratory that he had as part of his set-up in Boston. So all the products were checked over in his laboratory, and he guaranteed that they were pure and that they came up to standard. The manufacturer paid Harvard for the testing. That's how he got a dividend without having to patent. The patent policy by medical schools was not new. For example, Wisconsin had a patent on VitaminD. Lederle had some patents on some medical, other vitamins, I think Vitamin E. At any rate, he didn't want to collect a royalty, he didn't want to hold a patent.
Q: There was a Bureau of Biologic Standards at that time. They did not have the facilities to do the quality control?
Q: Was this arrangement made between Cohn and this Bureau of Biologic Standards that he would have the right? It's almost like giving the power--
Diamond: Quite possibly. I don't know the background of that, but they certainly always sent men up to see how things should be done, and they called him a consultant, took his advice.
Q: Do you recall any of the pharmaceutical houses that entered in to these arrangements with Cohn at this time?
Diamond: There were several of them. That was another reason why he didn't want the patent to be given to one place; he wanted all the companies to be able to manufacture the products that he had devised, by the methods he had devised, as long as quality control was followed according to his directions.
Q: Tullis had mentioned that Cohn was a personal friend of George Marshall's, and had spent a fair amount of time junketing between Boston and Washington.
Diamond: Oh yes. He was an advisor to the Defense Department. He advised on things other than just plasma. As far as I know it was all high powered secret stuff, so we never knew what he was about. But he traveled to Washington quite frequently.
Q: What was the status of the Red Cross at that time? It wasn't a government body.
Diamond: Oh, it never has been. But, they had headquarters in Washington, the National Red Cross building on 17th Street, where all their offices were. They had a local Red Cross chapter, too. They depended on volunteers.
Q: The blood collected for the blood banks in the first place was in terms of war mobilization.
Diamond: The Red Cross had to collect money -- they collected large amounts of money. But it meant more volunteers. They had to get volunteers at all levels -- they built up very good donor services. But they had to pay for it -- they in turn charged the hospitals to whom they gave the blood very little over their basic costs. They had a donor list that the Red Cross had collected for plasma. In due time the Red Cross collected about three-quarters of a million units of blood per year. A rival organization, at the American Association of Blood Banks, which at first was completely antagonistic to the Red Cross, collected an equal amount. So that we were collecting, eventually, a million and a half units of blood per year.
Q: Could you say something about this antagonism between the American Red Cross and the American Association of Blood Banks?
Diamond: The Association of Blood Banks helped organize local community blood banks outside of hospitals, or as part of a hospital service. They had blood bank experts who wanted to continue being directors of blood banks, and not working under the Red Cross. I had a very difficult time persuading them. I eventually persuaded most of the Red Cross blood banks and local AABB to work together. But it took quite a few years.
Q: What sort of arguments did you have to use to try to get them to work together?
Diamond: I appealed to the doctors. I was accepted by doctors, mostly, as another practitioner -- I was not a Red Cross person. Primarily, I was a pediatrician. By that time, I had gotten interested in this erythroblastosis and transfusion business, so I was recognized as contributing to therapy of infants and children --infants particularly-- and therefore was not stigmatized as a blood banker only.
Anyway, we did get them to work together. In some places they're still antagonistic. But usually one or the other is taken over. Here, for instance, in San Francisco, the Irwin Memorial, which is under the local medical society. That's what I was able to arrange in many places -- get the local medical society to take over the direction of the local blood bank other than the Red Cross.
Q: How do you spell Irwin?
Diamond: I-R-W-I-N. That's one of the finest blood banks. I was here many times trying to persuade them to work with the Red Cross. They never let the Red Cross in, and it still isn't in.
Q: This was a question, actually, of control over the blood supply?
Diamond: That's right. They did a tremendous job. Their medical director, Dr. Herbert Perkins, is a genius at running a good blood bank. They supply all the hospitals in this area, and outside too. He does a lot of good research. Anyway, that's the story of the Red Cross.
Q: Dr. Diamond, could you comment on the problems of funding for your hematological research during this time period?
Diamond: My Hematology Research Laboratory was funded first by small grants obtained by Dr. Blackfan. During the War, of course I had the support of research going on with Dr. Cohn. Although I didn't get money directly from him, he could give some money for a technician or something of that sort. After the War, the Hood Foundation gave us money. Although the first grant was for five years, they gave me some more money, and I continued supporting the laboratory that way. They were very generous to me.
After the War, of course, came the National Institutes of Health, which supplied funds. During the War, we had the OSRD, the Office of Scientific Research and Development. They supplied money to research laboratories having something to do with the War effort. When OSRD closed down after the War, the NIH took over. The NIH set aside money -- several million dollars -- to support hematology research laboratories all over the country. I was one of the first to receive a five-year grant, renewable every year, to do research on blood groups and on hematologic conditions in children. This money gradually was increased to the point where it not only took care of my laboratory needs, but began to support research fellows. Then they set up a research program, research fellowships -- particularly in hematology. They supported laboratories, which appointed research fellows for, usually, two or three years. There, too, I was one of the first.
So I started training fellows. I had trained them even to a small extent before the War. But after the War, beginning about 1947, 1948, I had money enough to train two or three fellows for periods of one or two years, and sometimes even for a third year. To make a long story short, from the time I started in the early 1950s, until 1968, when I retired from Harvard -- I trained 75 fellows.
Q: Dr. Diamond, I was wondering if you could talk about your blood research that led to your work with the Rh business.
Diamond: This development that arose at the Children's Hospital, and the Boston Lying-in Hospital, where I was a consultant for hematologic problems in infants. Over a period of five or six years, we had had about 20 cases of newborn infants who developed anemia, jaundice, and a lot of nucleated red blood cells in their peripheral blood. This had been first called "congenital anemia of the newborn." Children who did not show much anemia right after birth, but in the first week became very much anemic and required transfusions to survive. These have been reported as single cases, or as cases -- two or three -- that any doctor might have had. But it was a fairly rare condition in the newborn nursery.
Back in the late 1800s there had reports of cases of generalized swelling, or edema of the fetus and of the newborn. This was called hydrous fetalis. This too tended to run in families. It was blamed on various congenital anomalies. Some of them were born very anemic, with big livers and spleens. The pathologist often pointed out that their circulation was full of nucleated red blood cells. A pathologist in Germany said these were erythroblasts, meaning young red blood cells, and called it erythroblastosis fetalis, meaning
erythroblast in the fetus. Such children usually did not survive.
Also in the late 1800s, several obstetricians and general practitioners described children - infants -- that developed severe jaundice within the first few days of life, and often died of that and of anemia. Had about a 50 percent mortality. Some of them recovered entirely spontaneously. Those that developed anemia were given transfusions and recovered. This was called icterus gravis, meaning severe jaundice. This was recognized as being different from the transient jaundice of the newborn baby that a lot of infants have about the third to fifth day, and clears up by the fifth or sixth day. Icterus gravis was recognized to produce severe nerve damage in children, if children survived the jaundice.
Now in Boston, such children, whether they were born with jaundice or with anemia often were referred to me. We recognized that in some families, some children were born with hydrops and in the same family some were born with severe jaundice. I was able to collect, in 1932, 20 of our own cases, and in the literature over 200 references. We published a paper. Dr. Blackfan, and Dr. Baty and I. After 1932, reports in the literature called this "EF" and realize that it was one disease.
In 1939, Dr. Phil Levine made a discovery which we had missed. The cause of EF was a new blood factor, present in the infant but absent in the mother. She developed antibodies against her infants' red cells, which led to EF. This new blood group became known as the Rhesus Factor, or Rh for short.
End of Session.
November 18, 1986
Q: Interview with Dr. Diamond continued, November 18. Dr. Diamond, I was wondering if you could elaborate upon the significance of the work that was done in hematology, especially from the research angle, at Children's Hospital in Boston.
Diamond: As part of the program of training hematoloaists at the Children's Hospital in Boston, as each new trainee came on and learned something about various hematologic problems, and broadened his knowledge and understanding of the hematology that we were encountering, after a period of indoctrination -- sometimes a few months, sometimes half a year, sometimes even a full year -- the individual would settle into a research program with a special interest of his own so that he could -- he or she, we had women as well as men as fellows.
Q: Two questions. Where did the fellows come from?
Diamond: They all had had previous training in pediatrics or internal medicine. They applied for this Fellowship, which had become well established and pretty well known around the country since it really was the first of its kind after the War supported by the NIH. We had a number of applicants every year, and could only appoint two or three per year. But each, as she or he became proficient in general hematology and in pediatrics, would take on a research project of some sort. For example, two of them became interested in clotting problems and hemophilia, of which we had quite a number of patients. They worked in this area. They helped stabilize Fraction I, the first fraction of Dr. Cohn's isolation of plasma fractions. We began to use Fraction I as an anti-hemophilic fraction. It contained other materials than anti-hemophilic factor, which even to this date has hardly been purified completely.
Q: Dr. Diamond, could you expand upon some of the projects that were undertaken such as the work in hemophilia and in iron-deficiency anemia?
Diamond: There were several of my fellows who were studying the large number of patients with iron deficiency and other nutritional deficiencies as a cause of anemia. Iron deficiency was the most common and made up the largest number of patients that we had in one single category. There was also folic acid deficiency which we learned about later. In addition we had hemolytic anemias, blood destroying anemias, to work on. In the Boston population, where there is a large population of Italians, Greeks, and Mediterranean peoples, we had what was called thalassemia, or Mediterranean anemia. We probably had more such patients than any other city on the east coast short of New York. Then we also had sickle cell anemia because we had a fair number of children from the black population. So that there were any number of projects for researching.
Q: Could you say something more specific about the work being done on thalassemia, as well as on sickle cell anemia? How it is identified, why it's seen as an important problem, and what techniques were developed to deal with it?
Diamond: One of the individuals that came to work with me in Boston is very important in the study of thalassemia and of sickle cell anemia. That is Dr. Y.W. Kan, a doctor who came from Hong Kong. After Boston, he moved to California. He is one of the world's leaders in detecting the gene and the chemical basis for thalassemia. He has discovered how to isolate that particular gene and recognize it even in utero, and now it is possible to make this diagnosis at two or three months of gestation and advise on interruption of pregnancy if desired.
Q: Then did Dr. Kan first start working on this problem with thalassemia?
Diamond: Probably sometime in the late 1960s, early 1970s. He has continued on this, and has set up a large laboratory here. He is one of the people supported by the Howard Hughes Foundation, which guarantees his laboratory support. Dr. Kan is an example of a man who became interested in one particular project after he had rounded out his hematologic training, and has pursued this in depth to the point of uncover in a really, the genetic basis for thalassemia.
Q: This raises another question, which is the use of genetics itself within hematology. There are other instances earlier perhaps we'll talk about in a short while.
Diamond: Sickle cell anemia, of course, early on was recognized as a genetic defect -- heritable -- and was worked out by several people. Particularly of course by Linus Pauling finding the defect, for which he got the Nobel Prize, in the type of hemoglobin that caused sickling. Anyway, as these Fellows became skilled in general hematology, they did develop an interest in particular projects. I've mentioned at least four areas -- nutritional anemias, clotting defects, the hemolytic anemias, and the anemias of the newborn, which included erythroblastosis -- in which these men became proficient. Usually, after two, three, four, sometimes as long as five years, would leave for advanced positions in other schools. Of the 75 Fellows that trained in Boston with me, fully two-thirds of them eventually became professors of pediatrics or heads of hematology labs. In fact, five of them became professors and chairmen of departments of pediatrics. But the advance in knowledge in hematology came from the training that these Fellows received, and spread all over the country.
Q: Did you work out a specific method for training since this was a new medical experience, setting up the pediatric hematology services?
Diamond: No. The individuals -- all that came -- were trained or all previously trained in pediatrics. They couldn't come unless they had had one, two, or three years in pediatrics before they became interested in hematology. Then, at first they just helped us with patients with hematologic problems and learned hematology that way, and then they could start to work on problems of their own and publish papers of their own. There was no set program. It depended on case material. But there was always so much case material that in the course of a year or two they certainly would have covered all the important types of hematologic problems. Then, of course, when they became interested in a particular subject it was necessary to go back in the literature. In working up papers, they'd spend a lot of time in the library, and working with others, too.
Now, the question of the cause of erythroblastosis fetalis, or hemolytic anemia of the newborn, I've already touched on. I'd like to develop that further, because it's a good example of how knowledge accumulates.
Now, the antibody in the animal or human plasma is of two kinds at least, which we now know as IDG and IGM. The IGM is an antibody that acts in the saline suspension perfectly well, and causes clumping of red cells by the antibody in the dilute saline solution. IDG does not, but we didn't know that. When we set up the mother's serum in a case of hemolytic anemia of the newborn against the red cells of the husband, or of any individual, or of the baby, the IDG full of antibody which is present there did not clump in saline suspension. That's why we missed it all those years. The diluted the red cells in saline and the only antibody that might show up was an IGM, and that is not the type of antibody originally developed by individuals that develop antibodies against a blood factor.
However, I mentioned that in 1932 we cared for this baby with hemolytic anemia of the newborn (erythroblastosis fetalis), which was transfused with its father's blood. When we happened to try some of the mother's serum against the baby's red cells in a dilute saline suspension but not quite as dilute as two percent--ten percent I'd say--there seemed to be some clumping. However, on showing it to an expert serologist it was declared an artifact, not true clumping.
Now, Levine in 1939 had this patient whose baby had died of erythroblastosis at birth. She needed a transfusion. She received her husband's blood, and almost had a fatal reaction from it. Levine set up her serum against the husband's cells, in saline, and he saw no gross clumping. But in one area he thought there was some small clumps and when he studied it further, he found that she did have some sort of antibody against the red cells even in saline suspension. She was an unusual person, in that most of her antibodies against the factor on her husband's red cells were of a type that do not act in saline, but do act within plasma suspension. Most women who become sensitized through their babies have only this type of antibody. Once he had found it, we began looking for this kind of antibody. Everyone then realized that there was a new blood group factor to which the women had become sensitized through their babies, during gestation, and that this was the cause of the hemolytic anemia.
In the meantime, Landsteiner and Wiener had been injecting rabbits and guinea pigs with Rhesus monkey blood, which was Landsteiner's way of detecting blood group antibodies. They thus had found the M, N and P Factors on human red cells, but these were clinically unimportant. Because Wiener had used Rhesus monkey blood to inject the guinea pigs and rabbits, he called it a "Rhesus factor," and found that it did react in a very peculiar way against human red cells too. Then Levine proved that this was the antibody similar to, though not exactly the same, as Landsteiner's and Wiener's Rhesus antibody. Therefore Landsteiner and Wiener, and Levine too, called it the "Rhesus factor" in human blood. As Levine proved years later, it's not the same, though quite comparable.
Q: There was almost a twenty year period between the time that Levine first isolated this Rh factor and the time that he proved the non-identity between the Rhesus factor and the human.
Diamond: But by that time there'd been hundreds, if not thousands, of published articles calling this the Rhesus factor. Therefore it was difficult to change the name; it should have been called the "Levine factor" or Lord knows what.
Q: But this twenty years was also a period of very rancorous debate between Levine and Wiener. I was wondering if you perhaps could comment on that.
Diamond: It was more a one-way debate, because Wiener insisted on calling it the Rhesus factor, and insisted on several other ideas of his that were not quite acceptable to everyone. He wanted to name it the way he had devised Rh 0 for the most common factor, whereas the English -- through the skilled work of Race, and with the help of the great geneticist Dr. R.A. Fisher--found that several subfractions of what we call the Rh existed and eventually developed a very logical nomenclature for the Rh blood groups system.
Q: Could you, perhaps, comment upon what affect this work of Wiener had on the development of the research around erythroblastosis?
Diamond: It would be more the work of Levine. He set up a laboratory for blood grouping, at first in his own small quarters at the Newark Beth Israel Hospital, and then when he accepted a position with the Ortho Laboratories -- a pharmaceutical company in Raritan, New Jersey -- he solicited and received unknown serums from all over the country and all over the world. He developed one of the largest repositories of unusual blood group serums in the world. The rivalry between Levine and Wiener unfortunately was the result of Wiener insisting that his nomenclature -- Rh 0, Rh prime, and Rh double-prime, capital Rh, small Rh, and other such confusions -- should be the established international nomenclature. Most people preferred the C, P, E nomenclature of Race and Fisher and Levine.
Q: Why did Wiener push so hard for his nomenclature?
Diamond: Because he had named it first, he thought. Levine had accepted his naming it at first, until Race and his group in England showed that it was easier to deal with c,d,e -- that is little "c," little "d," and little "e" -- rather than "Rh prime," "Rh double-prime," "Rh 0," "Rh sub" Lord knows what.
Q: Do you think that this rivalry instigated by Wiener had any effect on the research programs of various labs?
Diamond: Just confusing.
Q: There was confusion.
Diamond: That's right.
Q: How long did this confusion last? Was it the work of the geneticist, R.A. Fisher and his group?
Diamond: Actually, people found that they preferred to use the C,D,E system.
Q: Dr. Diamond, could you please comment on the influence that Wiener ostensibly had with the NIH, in terms of his fight over nomenclature, the Rh factors?
Diamond: Dr. Wiener was a recognized world authority on blood transfusion and blood group factors, and had written the best book on this subject. This book was accepted all over the world as the bible for blood transfusions. Wiener wrote several good papers on transfusion reactions and a few on erythroblastosis. All his papers of course used the Rh 0 name. He insisted not only that his own papers bear this nomenclature, but he was a very aggressive writer. If anyone, particularly the English, dared use the C, D, E nomenclature, he was sure to write a few letters -- personal letters -- censuring them for doing that. He tried to persuade Dr. Levine not to accept the C,D,E system, to insist that it be the Rh 0 and prime, and insisted that the NIH back him in this. For a while the NIH did use that nomenclature only, but eventually they used both nomenclatures in preference to one or the other.
Q: What role did Karl Landsteiner play in all of this? He was mentor to both Levine and Wiener.
Diamond: He accepted the Rh 0 system. In fact he died before the C,D,E controversy had gone very far. So that he had no reason to enter the fight in any way.
Q: Could you peRhaps comment on the role that the work on Rh Factor played in development of the blood banks?
Diamond: The Rh Factor was the stimulus to re-awaken interest in blood group factors in humans. Thereafter using these newer methods of detecting antibodies present in plasma of sensitized individuals, numerous factors were discovered in humans. As a cause of transfusion reactions, and as a cause of hemolytic anemia of the newborn due to maternal antibodies against the fetus, and against the newborn baby. More than three hundred different blood group antibodies have been discovered in human beings. The English, particularly Race and Sanger -- in London -- working in their Serology Laboratory--became internationally famous for detecting some of these rare blood groups. Then the next development from that, the realization that blood group antibodies were mostly of the IgG type that did not react in saline, led to a further extension for the blossoming of the research on antibodies and the extension of immunology as a tremendous field for research and for practical clinical developments in the field of immunology and genetics. Departments of genetics, departments of immunology just opened up all over the world as a result. Although it wasn't the sole reason for development of immunology and genetics by any means, it was one of the factors that helped boost the interest in antibody research.
Q: Could you comment on the particular role that the identification of Rh factor and blood-typing played in the development of blood bank systems?
Diamond: Blood banks after the war became established as a necessity for the treatment of numerous conditions -- not only replacement of blood, but hemolytic anemias where blood destruction went on, and other areas in which immunology was vital factor in the understanding of disease processes. Blood bank directors, blood bank technicians, blood bank scientists were established in routine laboratories in all large hospitals. True, the American Association of Blood Banks and the Red Cross in many cases supplied the blood through their established organizations, but even in these hospital blood banks, research work in immunology was pursued. For example, here in San Francisco, Dr. Perkins, who was the scientific director of the Irwin Memorial Blood Bank that supplies so much of the blood in San Francisco and in the whole area, has several good research workers and in fact is also on the faculty at the U.C.S.F. medical school and helps guide some of the research in immunology, and in blood banking. We have our own blood bank here in the hospital, but we get all our blood from the Irwin Memorial and we just distribute it here and make sure it goes to the right people and so on. So that this was a tremendous boost to the field of immunology and to the field of genetics, which certainly would have taken years to develop if not for the stimulus of new blood groups and blood banks, where such material had to be very carefully analyzed in order to avoid serious transfusion reactions.
Q: An interesting point is raised here. We've seen in a number of instances where important conceptual foundations for a new discipline of hematology was laid by work done by practitioners in other fields. You had physical chemistry and techniques, introduced by someone like Edwin Cohn. You have the work done in genetics, Mendelian genetics, around Rh factor, around thalassemia, around sickle cell anemia. You have the work of Landsteiner and his group in immunology. Are there other such cases where this is borrowing, or transfer, of important techniques and theories from other fields?
Diamond: Oh, there must be several different instances of this kind. I'm not familiar enough to be able to translate it immediately. But now the genetics, the method of probing for genes -- the location of genes, the inheritance of genes, how genetic engineering can be stimulated -- are all examples of the same development. The ability to manufacture anti-hemophilic globulin for example, the ability to manufacture the human growth hormones, and outstandingly the ability to manufacture insulin are good examples of how this has carried over. This is really the future of medicine. We will have methods of treating any number of diseases.
Q: If I might follow up on this question. It's clear that there's this transfer of concepts, and transfer of techniques or technologies, if you will. The other aspect that would be interesting to delve in to a bit is the institutional context. I don't think that transfer would be possible unless there were institutions set up that could allow for this interdisciplinary approach. This might, perhaps, have laid the foundation for hematology as a self-conscious discipline. I was wondering if you could speak about your own experience at Children's Hospital in Boston, going back to the 1930s and 1940s, where you were in a position to come into contact with the latest in the scientific developments, and how you saw your role during that period?
Diamond: Various foundations have been set up over the past dozen or more years, increasingly now, to support research by giving money for research laboratories -- even for putting up buildings in which research laboratories can be established. In Boston, for example, we have what is now called the Enders Building, named after John Enders -- who recently died. He was the man who developed polio vaccine, to prevent infantile paralysis, which used to be a great scourge in medicine and crippled thousands of people, children particularly. He also developed a vaccine for measles, and German measles. That was the sort of thing that developed. Various agencies, and various organizations were set up to sponsor such laboratories.
Then, to mention just one other -- one of many, this is the largest one -- the Howard Hughes Foundation has billions of dollars. They also established Hughes Fellowships, given for five years to gifted research men. Now not just the Hughes Foundation, but several other similar foundations are giving money not just for research work, but for bricks and mortar that are necessary, and continued support for research. So this, really, was an outgrowth, if you want to think of it so, of the blood bank, RF, blood grouping, and IgM, IgG, and other immunology research that came along with this. You might say it wasn't just that, but the blood bankers and the hematology research people like to think that this was the stimulus that got things started in that pattern.
Q: This corporate interest in development of medical sciences, through philanthropic foundations, through the allocation of funds, etcetera. Has that gone through different cycles? Certain times more money comes from corporate sector as opposed to other times? Has that affected the types of research in any way?
Diamond: Only to a very limited extent. That possibly -- I don't know that this is so--maybe Eli Lilly is more likely to support research in the field of insulin, or something of that sort. The Ortho Laboratories did sponsor some research in blood groups, but very little comparatively. These pharmaceutical companies are working more closely with research organizations, because eventually it'll be to their interest. Now a good example of that might be the fact that the Lederle Company was the original sponsor of research with anti-cancer drugs, particularly methotrexate. That came about in an interesting way, too. Dr. Farber, the pathologist at the Children's Hospital in Boston had always been interested in cancer in children. Our interest in leukemia was close to his heart, too. A research finding that he made was that if you gave large amounts of folic acid to an individual with a certain type of cancer of the lung, the cancer cells grew more rapidly. In so doing, they outgrew their blood supply and the cancer started degenerating.
Q: With the folic acid.
Diamond: With the large doses of folic acid. He wanted to pursue that. Folic acid was being manufactured in part by the Lederle Company. They had a research man named Dr. Subbarow--S-U-B-B-A-R-O-W--at Lederle Laboratories. They offered Dr. Farber the opportunity to get Dr. Subbarow off to Boston to work on folic acid. Dr. Subbarow and Dr. Farber, said, "Why don't we try something that will prevent folic acid from stimulating this -- an anti-folate." Dr. Subbarow came up with an anti-folate, which indeed in animals prevented the cancer from growing because cancer cells needed folic acid to grow. So this anti-folate, a very toxic material unfortunately, could then be tried on some human cases and, although its toxicity was such that it couldn't be used routinely in a large enough dose to help everybody, it did slow down the growth of tumors--particularly leukemic cells. Dr. Subbarow proceeded to develop a half-a-dozen different anti-folates, and eventually came up with one that was much less toxic. This eventually was the material now known as methotrexate.
Q: Was this work done-
Diamond: In Boston.
Q: In Boston. Not in the Lederle Labs.
Diamond: That's right.
Q: But Subbarow is still associated with the Lederle Labs.
Diamond: Right, and they sponsored Dr. Subbarow's work. He was their employee, in a sense, even though he worked in Boston at the Children's Hospital pathology lab under Dr. Farber. At that time, I was setting up the National Red Cross blood banks. This would have been the early 1950s. Although I was involved -- I came back and forth to Boston, and I still had charge of the leukemia cases. One of my men, one of my trainees, took over the responsibility for this treatment that Dr. Farber's anti-folate, methotrexate, was used on. That's how that developed. Lederle Laboratories still, of course, manufactures methotrexate, which was one of the first drugs.
Q: So what we're actually seeing here is a process that might have begun as early as the 1930s with Hood Milk Company, and perhaps earlier. But especially during the 1940s and 1950s, we see a definite interaction between university-based research and different interest relationships.
Diamond: That's right. Slowly developing and expanding, so that now there are dozens and dozens of such joint ventures.
Q: So it's not as contemporary a phenomenon as is often suggested. It's not something just of the 1980s or the 1970s.
Diamond: Oh no. It really goes back, if you want to start it, way back in the early 1900s when serology and immunology and bacteriology really began to blossom.
Q: So this hybrid field of hematology actually played a central role in this development.
Diamond: I feel so. Now, let me go on to the further development, which I think is important, of erythroblastosis fetalis. After Levine showed that the so-called Rh factor was the basis for it, we of course began using only Rh negative blood for the transfusion of the infants with erythroblastosis, or hemolytic disease from the action of maternal anti-FH on the infant's Rh positive blood cells. The way to treat such children, obviously, was to give them only Rh negative blood because some of the maternal antibody against the Rh positive cells of the infant would have carried over and be present in the infant's systen, and would remain there until it was used up--which took a matter of two, three, four weeks or so of gradually diminishing. Meantime, Rh negative blood was necessary to protect the infant's circulation against the reaction of this anti-Rh which the mother had given it, in-utero. Now, the best way -- Dr. Wiener, as well as we -- decided was to remove the infant's Rh positive blood and the serum containing the infant's plasma containing the Rh antibody acquired from the mother, and replace it with Rh negative red cells which could not be damaged, and which the infant could live on until the anti-Rhwas all gone. Then the infant's own Rh positive cells would not be destroyed. Dr. Wiener dissected and cut an artery in the newborn infant's wrist to withdraw blood, and at the same time put blood in -- Rh negative blood -- into a small vein in the other arm. This was a traumatic, difficult procedure. Me in Boston, in my laboratory particularly, decided that we wanted to do this using one of the very prominent, obvious veins in the umbilical cord -- the stump of the umbilical cord. First, we tried using rubber catheters, but these didn't work too well because the blood would clot in the rubber. About that time, plastic material became popular. Our neuro-surgeon, Dr. Frank Ingraham--I-N-G-R-A-H-A-M had developed a plastic material, manufactured by some plastic manufacturer that was non-clotting surface. In other words a smooth surface on which blood did not clot. He suggested maybe I should try this for blood. I did. He had shown that blood didn't clot too quickly -- it took fifteen, thirty minutes before clotting took place. So we tried a plastic catheter in the umbilical vein, threaded that in, and it worked beautiful. We could do a complete exchange transfusion in an hour or so, withdrawing ten ml, or twenty ml, at a time and replacing it with 10 or 20 ml of Rh negative blood. This exchange transfusion, or replacement transfusion, became the standard method of treating erythroblastosis fetalis -- by exchange transfusion. Of course you could use it more than once, even a half-a-dozen times if the baby needed half-a-dozen transfusions, using the umbilical vein.
Now that led to an interesting and important development. That is that in newborn infants, where they need blood repeatedly to measure oxygen, C02, and any number other factors, now instead of drawing blood by a needle every time, they thread an umbilical catheter into the umbilical vein, or cut down on another vein if the umbilicus isn't available. This has become the standard method of monitor in a blood changes in the newborn, and in older children too -- using plastic catheters and leaving them through small needles, or just cutting down on a vein and threading in a catheter and leaving it there for one, two, three, four days or more. These catheters can be sterilized and used without fear of contamination. This has been an important development in the management of newborns and of small infants--and particularly in premature infants, where you're dealing with tiny veins that would be difficult to catheterize ordinarily. It has made a great difference in the mortality of premature infants and of sick babies in the first few weeks of life.
Q: How long would it take for such a technique to diffuse through medical --
Diamond: Remarkably fast, because -- originally it took somebody like Wiener to do an exchange transfusion using his cut-down method. A fellow named Wallerstein developed a method of doing transfusions using the sagital suture, sagital vein in the head. But this too was dangerous. So, this diffused to the point so rapidly that house officers were doing the same transfusions. The time was reached when instead of my special Fellows, who for the first three or four or five years were called on to do these same transfusions, this was done by residents on the service Eventually, the pup, or the lowest resident, was the one who had to do the same transfusion because it was such a chore. It would take an hour, an hour and a half, to do gradually, of course. It's standard technique. I should think all this really spread within five or ten years. All around the world. Maybe within five years, really.
Q: So once again we see the introduction of new technique leading to a whole redefining of the working relations within a hospital setting. We had a similar case with the indirect transfusion, with the development of ACD system.
Diamond: Sure. Anybody could do it. Now anybody can tap a vein in a newborn, or an artery--arteries as well as veins are threaded with plastic catheters and left.
Q: Was there any resistance of the type that came up against the indirect transfusions because of the existence of pyrogens earlier. This was a much smoother--
Diamond: It was accepted as the standard, non-traumatic way to do blood transfusion.
Q: What did it do in terms of hospital supplies? This is a new product - plastic -- being used in a new area.
Diamond: Right. Then of course plastic bags instead of bottles for blood transfusion became popular. We too were the first to use these -- first in Boston -- and then all over the country. Fenwal Laboratories in Chicago began putting out plastic bags already connected with tubes, so you didn't have to clean tubes and wash them and cut down transfusions--made transfusion technique very simple and very non-traumatic.
Q: So this would also contribute to what we discussed earlier -- the development of central supplies in hospital.
Diamond: All blood -- all fluids are now given out in plastic bags that the manufacturer can produce much more cheaply in bulk, and can sterilize, and guarantee them by their testing that these are sterile, used over and over again. Surely, it's made it more expensive to give transfusions when you have to use a disposable bag and disposable tubing. But it's so much safer. If you ever have even a mild transfusion reaction, you never want to have another one. So this has changed the practice of medicine to a great extent. Can even be given in the home, rather than having to hospitalize a patient.
Q: If we were to break down the early blood banking system into a series of different techniques borrowed from contemporarily developed technologies, as we did with the development of plastic tubing, plastic bottling, which other areas would we be interested in researching? There would of course be the question of refrigeration, I would think. Preservation.
Diamond: Yes. Now, of course, preserving blood for emergency need in case of earthquake or atomic bomb attack, and so on. In thousands of units! First, of course, there is the use of new diluents and preservatives, so that blood can be stored for 35, 40 days or more. But that isn't enough protection -- in case of a disaster you want something that can be stored for a much longer period. Therefore the freezing of blood cells became an important field of investigation.
Q: When did this research develop?
Diamond: That's been going on ever since the 1950s. But certainly in the last ten years, maybe longer, freezing of blood cells -- especially preservative solutions -- is a standard practice. All blood banks now have stores of frozen cells.
Q: You mentioned diluents? Is that--
Diamond: Yes. The various diluents, or preservative solutions.
Q: Could you spell that please?
Diamond: Diluents? D-I-L-U-E-N-T-S.
Q: The research on these different aspects of the blood banking process was done mainly where? In research labs connected to universities, industry?
Diamond: Research labs connected to universities, and hospitals. Hospitals were, of course, most interested in this so they could have supplies of blood for an emergency. Like the fire in Boston that destroyed that night club, the Coconut Grove, and so on. They needed much blood then, and they had to go out and bleed people. Whereas if they'd had frozen blood they could have brought it in a hurry. They use frozen blood for emergencies, and also rare blood groups! Also, there are people with rare blood types who have antibodies against the common blood groups. For them, you have to have a storehouse of rare bloods. The AABB and the American Red Cross have established such repositories of rare blood. They keep it and ship it all over the country, all over the world if there is a demand for it. That sort of thing.
Q: Dr. Diamond, we talked already somewhat about the relationships between the hospital and medical school and corporations. I was wondering if you could talk about, in terms of your own experience, the relationships that were worked out between the hospitals and the university, and medical school.
Diamond: This was an interesting development. I don't know when it started. It must have been in the early 1900s when the new medical schools like that in St. Louis, Washington University, that at Hopkins of course, University of Pennsylvania, appointed full-time men in the clinical fields to take care of specialties in the hospitals. In order to use these men, and use the patients too, for teaching purposes of students that went through the medical school, the teachers in the hospitals had to be members of the department in the medical school. The chief of, let's say, pediatrics at Harvard's Medical School was the man who was also the chief of the clinical department at the Children's Hospital, or at the Massachusetts General Hospital of Pediatrics. He had the privilege of recommending not only the clinical staff at the hospital, but also the teaching appointment, so that he could teach the students from the medical school who would come over in the third and fourth year. So that the recommendations were joint recommendations for a position in the hospital as clinician in a special area, and as instructor, assistant professor, associate professor, full professor -- going up the ladder -- in the medical school. That would pass through the faculty, where of course the C.V.'s and the attributes of the man could be reviewed. For example, if I had a man whom I had appointed as a trainee in the hematology laboratory and he was very good and I needed assistance, as I did time and time and again for the increasing load of patients at the hospital, I would recommend him for an appointment as an instructor in the department of pediatrics at the medical school, and recommend him to my boss -- my professor and chief of the hospital clinical department--to put through for an appointment at the medical school. Generally, of course, we wouldn't put through anybody that we couldn't recommend and document very carefully. Of course very rarely--in fact I don't remember ever did we have one of our applicants turned down. Once a man had received an appointment at the lowest rank -- an instructor in pediatrics at the medical school, and an assistant physician at the hospital -- then in due time, when he produced good work and could document it, he would be recommended for promotion. At Harvard, promotion was very slow. An associate professorship was a tenure appointment. That is, once you became an associate professor at Harvard, in the department, you would only lose that by either moving elsewhere or by doing something awful, which never happened in my recollection. But associate professor was tenure appointment and then full professor, tenure appointment. Then the chief of the department had to make sure that there were funds to support that man from his budget or from special grants, permanent hospital appointment.
Q: What was the early basis for the funding?
Diamond: The medical school had its budget. I don't how many million dollars. Each department is allocated a certain amount of money. The chief of the department knew how much money he had to spare, and how much he could assign to different individuals. But he had to have the money! He couldn't put through an appointment without also showing where the money was coming from. In some cases the hospital, in order to have somebody take care of patients with certain diseases, would allocate money that it had. Either out through a grant, or through a permanent endowment for taking care of the man. Sometimes he got part of his salary from the hospital, and part of his salary from the medical school. But you always had to have the money to support a man that you recommended for a position. They wouldn't approve a physician for which there wasn't money available so that the man would suddenly be hung up. It happened occasionally! Then the man would have to move elsewhere. Or you'd appoint a man for five years, and say, "The end of that time you either will have to generate some funds one way or another--research funds -- with your clinical ability -- or you'll have to move elsewhere." That is bad for assistant professors. Assistant professors are not appointed for more than five years for that very reason.
Q: In the days before big government funding through the NIH and the National Science Foundation, what might have been the major sources of research funding that would have come in to your labs?
Diamond: The NIH had some of these permanent funds. They'd give research professorships.
Q: Beginning how early?
Diamond: Oh, I don't remember when it started. I think way back again in the 1960s they put money aside in their budget to fund the research professorship in medical schools all over the country. You had to apply for those, but once they gave it to you they guaranteed that it would come hack year after year. They were careful not to fund more than what they could put in to their budget.
Q: If we went hack to the 1930s, what might the resources have been.
Diamond: The only funds then would be hospital generated.
Q: This was from fees?
Diamond: From fees, or from donations. The Children's Hospital in Boston had a corporation of members, wealthy families that could be depended on year after year to give money to the hospital.
Q: How were these funds allocated? Was there any strings attached as to what the funds could be used for, or was it at the discretion of the institute?
Diamond: Occasionally it would be just for work in asthma, or for taking care of patients with certain diseases. But most hospitals would refuse to accept limited funds like that, because the time might come when they didn't have such patients, and didn't use up such funds, and had to have more generally allocated funds.
Q: Did this ever present a problem for the research that you were responsible for in Boston?
Diamond: It certainly did, from time to time the head of the laboratory or the head of the research project would have to get out and scrounge around for money. Generally, we tried to have a few places we could call on -- like the Hood Foundation -- for help, or individuals that we tried to persuade to give permanent money, so that it would be in our treasury and we could draw on the interest of that. It depended a good deal on the ability of the individual. Some people were much more adept at that than others.
Q: What about during the Depression years? Were there any particular problems, in terms of funding, during that period?
Diamond: And how. [laughs]
Q: Could you expand on that a bit?
Diamond: I remember, I was married in 1929, which was the heart of the Depression. If not for a working wife, and for a couple of fellowships that I was able to get one after another, we would have had to close up then. But we were able to get private funds, and we were able to call on hospital finances to help support us to some extent. I never did have to get support for the hematology laboratory from the hospital or medical school. I always was able to get some private resources.
Q: What was the main source of the private resources?
Diamond: Patients' families. Actually, eventually you know at Harvard that this was true, but when I came out here some of my old patients wanted to establish something that would be permanent. So they got together. Harvard demands an endowment of a million dollars for the establishment of a permanent chair. Here they would accept 500 hundred, or 350 thousand, to begin it. They established the "Louis K. Diamond professorship" here from patients and friends that gave money. Some of them promised to give monies several years in a row. But there is this professorship, and I'm pleased that Y.W. Kan is the Diamond Professor of Hematology.
Q: That's quite an honor.
Q: Could you talk about the relations that existed on the intellectual front. Perhaps draw upon the experience you had with Edwin Cohn, during the World War II period. His plasma fractionation project, I understand, was quite an interdisciplinary type of project, drawing upon people from different universities -- MIT, Harvard, Boston University -- as well as different intellectual inclinations. You had the basic researcher in protein chemistry, you had people interested in hydrodynamics, and you had people interested in material sciences. Was this something new?
Diamond: I think it was. I'm not familiar with any similar organizations elsewhere. Quite a few were founded afterward modeled after his. But when he came over to the medical school, and set up this protein foundation -- so-called, it had a more elaborate name -- he was very careful not to spread himself in to other areas. He stuck to protein chemistry and protein research. But, he did accept qualified people, often men who were professors in other institutions, to work with him for a year or two or three, and learn how to do things and then go back to their own organizations and set up similar laboratories; laboratories modeled more or less after his, but in a different area of scientific interest. But he was very strict in not allowing his men to spread themselves in to clinical areas in his laboratory. At the same time he had clinicians associated with him, would come to weekly meetings--his weekly meetings were, as Tullis probably told you, were tremendous. He'd have a representative of the Surgeon General's office of the Army, of the Public Health Service, of laboratories elsewhere. They were meetings, usually, of 30 or 40 people. But, his was a model for research which could then go out in to the field. He'd have the professor of pediatrics, Janeway, as a regular member of his group and come over every week. Dr. Cohn was likely to call up to find out how a project was going, any time of the day or night. We had foreign students who were always awed by having a professor call up at night to find out what had happened to a laboratory project. One foreigner, I remember, at one o'clock in the morning got a telephone call: they said "Dr. Cohn is on the line, he wants to know about something." "Hold him a minute," and he went and put on his necktie [laughs] and his coat, because he wouldn't go over to the phone without being properly dressed to talk to Dr. E.J. Cohn. But Dr. Cohn kept close tabs over what was going on in the laboratory, and didn't allow men to spread themselves and forget the project that they were working on. That's how he got good results. But laboratories like his were established all over the country, modeled on his organization.
Q: How did he overcome possible resistance from institutional bureaucracy?
Diamond: All he had to do was call Cr. Conant, or call Dr. Edsall, call the highest power. He didn't hesitate. He had close contacts. In fact he could call the head of the NIH or the Surgeon General of the Public Health Service, or in charge of the Navy or the Amy, and say "I'd like this done," and the man would do it. Otherwise he'd raise such a fuss with others that the man would find it uncomfortable.
Q: What was the basis for this prestige? It wasn't simply his research work.
Diamond: No, because he had contributed albumin, gamma globulin to the Navy. He contributed methods of working on chemical problems to the Army, for the Public Health Service and so on. He was so well recognized all over the world that he could call up Europe, too, and suggest strongly something be done in a certain way. When we were due to have an international hematology meeting --international blood transfusion meeting--in Paris, he and I and three or four other people were flown over there for this meeting in the old Constellation planes. We had to put down in the Azores, and in Labrador to refuel going and coming. Way back in the middle of the War. But he could call up and say, "I'd want so and so on the program," and there'd be no question. They'd make room for so and so on the program.
Q: There must have been something more to his abilities to work between government, industry, and researchers.
Diamond: He had contributed materially to national and international research organizations. They knew that they'd get something out of it. They never were asked to do something gratuitously.
Q: He also seems to embody certain organizational skill. That's not necessarily the forte of research scientists.
Diamond: Oh yes. He set up new organizations if he needed to. He set up organizations to build mobile blood units - trucks -- that went around and collected blood in various places. He conceived all of that. I traveled around with him for quite a while. I would be awakened, in the middle of the night he'd have an idea he wanted to start the next day. Sure enough the next day he'd start it. If you said, "That's too soon" he'd say, "No, it can be done." It always was done. He was a power.
Q: Could you perhaps give some background in some of the key figures you came to know who had worked with Cohn. You mentioned earlier--
Diamond: There was Dr. Oncley, who went to Michigan eventually. He worked with Cohn for a dozen years. There's Dr. Edsall, of course, from our own U.N.W. I can't name all of them, but there were people from MIT, from Cal Tech out here, from Wisconsin there was a famous protein chemist whose name I can't recall, from Michigan, from Chicago. They came and spent variable periods with him, and then would go back and set up their own organizations and continue their work. That was another point. He never hesitated to take a phone call from somebody at a distance who had some problem, and he would help with it. If he couldn't help, he would suggest one of his men who could help either by telephonic advice or to go out there! He always was willing to help somebody who had a problem.
Q: Could you say something specifically about your work that you did during the World War II period?
Diamond: Well, Cohn had various people working on various things. For example Dr. Janeway, who was interested in immunology, worked on the globulins -- gamma globulins particularly. Dr. Tullis worked on blood preservations, methods of preserving the red cells. I worked on the clotting factions, and the blood group factions. We purified and concentrated anti-Rh -- anti-A and anti-B -- and made them available for commercial manufacture.
Q: Were new techniques entailed in the production of the anti-RH anti-A and anti-B.
Diamond: No. That was fairly standard; just purification. The biggest problem -- which we never solved, and it still hasn't been solved -- was how to purify and fractionate the Factors VIII and IX, that is the anti-hemophilic classical factor and the so-called Christmas factor, or factor nine. It just now is being worked out. The factor eight is a tremendous, lengthy protein. It breaks down so easily that it never could be fractionated in pure form until very recently. But now it is purified, and they can manufacture it in the laboratory. But that was my problem. Early on we did purify factor one, fibrinigen. That became a very useful product in rare cases of women who developed a paucity of fibrinigen and would have bleeding during pregnancy, particularly toward the end of pregnancy with toxemia. They develop low fibrinigen levels and might bleed to death. We purified, through Dr. Cohn's laboratory of course, Fraction I. It was the first thing that came down--that's why it was called Fraction I. whereas the globulins were Fraction II. Albumin was Fraction V.
Q: As you produced these different fractions, what was the actual process in getting them into circulation, in to use?
Diamond: That's why he had Janeway, who had patients at the Children's that were deficient in gamma globulin, immune deficiencies. He had clinicians at the Brigham and the Mass General and the Boston Lying-in, who would test these on human subjects after they had been through all the necessary laboratory test and the necessary animal tests. He had contact with people all over the country who could work on the clinical problems with the fractions that he produced. They were never hazardous--always very carefully documented. In those days we didn't have human experimental committees, but they were just as strictly guarded as they are now with human experiments. We didn't ask signed permission to try things out, but I never gave the fibrinigen or anti-hemophilic fraction to anybody that hadn't given permission. Verbal if you wish, but they were indebted to me and I could always rely on them.
Q: Were there different standards of quality control and testing that were brought in to existence during this period that hadn't existed previously?
Diamond: The best that could be set up by a combination of clinicians and laboratory people.
Q: Were these procedures discussed at these meetings?
Diamond: Very thoroughly.
Q: Was this part of the Thursday meetings?
Diamond: That's right. And special meetings. Nothing was ever done that didn't have the approval of a committee. Dr. Cohn never decided things on his own when it involved patients. Because he was not an MD -- he was a PhD. He knew more about medicine than many MDs. But he knew just about as much medicine in his special fields as anybody did, and could make suggestions that were clinically relevant.
Q: Did he work in a similar manner in the areas of basic research? Did he also form committees there and consult?
Diamond: Yes. Oh, he often made decisions on his own -- he knew best.
Q: For basic research, as opposed to clinical.
Diamond: Yes. But otherwise he always formed committees. The committees always asked him what he wanted, and made sure that he approved what they decided. He would guide them, but he would never establish a rule without support proper authorities.
Q: Dr. Diamond, I was wondering if you could comment on this overlap, or perhaps lack of overlap, of interest between newly self-conscious hematologists and the practices of pediatricians, and especially concentrate on what types of anemia were most prevalent in you own experience?
Diamond: The so-called nutritional anemias, dietary anemias -- or as it developed without much question, iron-deficiency anemia -- was the most common type of problem that pediatricians encountered. This was because when breast feeding became less popular, and women were persuaded that the baby could grow and gain just as well on bottle feeding, and be less of a nuisance to the mother, give her more freedom, the milk formuli were canned milk or powdered milk diluted with water to which sugar was added -- dextra maltose, or some other form of manufactured sugar supplement. Babies would be fed this with complete satisfaction, and it would be easy to manage. Anybody could give the baby the bottle! But, the ordinary formula -- cow's milk formul a-- contained so little iron that unless the child were given iron-containing foods, iron deficiency could develop, particularly as the child grew and needed more iron to increase the number of red cells in its expanding circulation. Iron deficiency anemia, particularly in the foreign born population that didn't use breast feeding once they could be freed of that task, and used canned or bottled milk, which was much cheaper, allowed anemia to develop very slowly - -undetectably, often--with the child developing less than half the amount of hemoglobin that it needed while it was growing, without the parents being cognizant of it.
Q: Where did the push to do away with breast feeding primarily come from during that period?
Diamond: Chiefly from the formula manufacturers and the canned milk manufacturers. The milk companies them too; they put out propaganda of that sort. You know, abroad it became a scandal, that canned milk was given away at first to persuade the women to give up breast feeding and then buy canned milk at much greater expense than ordinary bottled cow's milk. So that we encountered iron deficiency anemia very commonly. Particularly in the foreign-born population when they first settled in Boston and vicinity, or New York and vicinity. Not until the late 1950s really, when cereal manufacturers began to put iron into their cereals -- not until these fortified cereals came on the market could we be sure that iron was being given in sufficient amount. Often they'd give spinach or green vegetables, but children didn't eat too much of that. They might have gotten a little iron, but not enough. Iron deficiency was a serious problem. Of course infection, occurring in children that were already anemic, would interfere with their absorption of iron or their utilization of it. Therefore a combination of iron deficiency, poor diet, and infection --prevalent so often -- led to the high incidence of iron deficiency anemia.
Q: What was the attitude of the community physicians toward this push to do away with breast feeding?
Diamond: They often had very liittle to say about it. But often they would say, "You don't have to breast feed the baby! You can do just as well by formula. You don't have to strap yourself down this way."
Q: So outside of pediatricians, the clinicians who were particularly interested in nutritional anemias, large numbers of physicians would go along with the--
Diamond: Would say, "Don't bother with breast feeding. You can do just as well -- look how well the children grow on bottle feeding." But they'd forget the necessity for iron. Maybe as early as the third month of life, when the iron stores that the child had become so depleted that the child was actually seriously iron deficient.
Q: Could you give an approximate date for this change from breast feeding to formula feeding?
Diamond: I think probably it was the early 1900s, or the mid-1900s. Particularly, of course, with the advent of the depression in the 1930s when women had to get out and work, or do something to increase the income of the family. We must have had usually five or six iron deficient children in Infants Hospital anytime we wanted to look for them in the 1930s. It was our biggest problem.
Q: Was there research interest in linking the lack of utilization of iron and the rise of infectious disease during the 1930s, or was that a later concern?
Diamond: That came a little later. But, there were a lot of problems in introducing iron into foods--bottled, canned, and powdered foods. So that it took a good ten, fifteen years before that was overcome.
Q: The interest in general among doctors on questions nutritional was definitely not centerpiece in the training of the period.
Diamond: No. That was the trouble. Doctors were not trained in pediatrics to supplement foods to make sure that the children got a balanced diet, balanced in all the requirements so that they could grow well. Poor people, of course, their diets were often very deficient. Just milk, water, and sugar.
Q: So these examples of nutritional anemia became strikingly apparent during Depression years.
Diamond: Yes. And thereafter for quite a while! Right in to the Second World War, and after that with the explosion of population. The food manufacturers really had a heyday -- sold all sorts of formuli, some of which were not so good.
Q: Were there any problems in terms of funding? If nutritional anemia was seen as a problem of poor people, would there he an interest by the various agencies who would fund research at that time?
Diamond: Not much. It was too humdrum, too unexciting, too matter-of-fact. Didn't have the appeal.
Q: Was there a change at some point in the attitudes toward the nutritional deficiencies and anemia, and how did that come about?
Diamond: Yes. I think people began to realize that nutritional deficiency was widely prevalent, and that infants and children had to be fed a diet that contained all the necessary ingredients for growth and good health, and good levels of everything. So, parents became very cognizant of this. A lot of books came out by experts, and less excerpts, that recommended various regimes. I think we've had very little trouble in the last 20 years with that sort of problem.
Q: Dr. Diamond, your career in pediatrics and hematology has spanned a period of time in which hematology was transformed from being a sub-specialty within internal medicine to becoming a self-conscious discipline with its own professional society, the American Society for Hematology, with its own particular journal, the Journal of Blood. This came about by people from various different areas, different concerns -- whether in pediatrics, whether among nutritional concerns, biochemistry, etcetera-coming together in a professional society. I was wondering if you could perhaps recap some of your experiences in terms of the building of this professional society, talk about what role it played?
Diamond: Although, as I mentioned previously, the largest number of hematologic disorders, whether they result in infancy or childhood of nutritional deficiency, and iron deficiency particularly -- to some extent even folic acid deficiency -- with the knowledge disseminated of how to avoid and to cure such nutritional deficiencies producing anemia, it became more common for the pediatric hematologist to be consulted or referred on about patients with anemia that was not due to nutritional deficiency. Of course, in this category we have the leukemias in infancy and childhood. Leukemia can occur even in the newborn, and we would therefore have to face the problem of how we should handle malignancy that was associated with anemia in the infant's and child's age. It became important for the pediatric hematologist to learn how to recognize these and to learn how to treat these as methods of treatment were developed for producing remissions -- not cures -- of malignancy in infants and in childhood. As all ready mentioned, methotrexate was one of the early drugs. In contrast to that, in the adult practice, the hematologist often found that the patients with oncologic conditions-- malignancies--did not develop anemia and the patients were not referred to hematologists primarily, but would be picked up by internists or people who became specialists in the management of malignant diseases. The variety of drugs now which -- certainly at least a dozen which can control cell growth to some extent, and may control the spread of malignant tissue. X-Ray, of course, the therapy and the use of radioactive materials. Now, the use of immunologic materials like specific antibodies against particular malignant cells. So that oncology in the adult became a necessary specialized study independent of hematology, because such patients didn't necessarily develop any evidence of hematologic disease.
Q: This bifurcation that takes place in terms of adult cancers, between oncologist and hematologists, did this change the complexion of hematology as a discipline?
Diamond: It did, at the adult level. Because different drugs, different methods of managing, different methods of detection became so necessary that the oncologist just had to learn how to diagnose, how to determine beyond doubt, how to treat malignancies often in various organs.
Q: Did this lead to a change in who the various practitioners associated with, in terms of professional societies? What I'm trying to get at is did, at an earlier stage, this American Society of Hematology play a role in bringing various different types of practitioners together as hematologists, and at a later stage was there this bifurcation, this split in to new professional societies?
Diamond: In the pediatric age group, there are relatively few disorders that are malignant excepting the kidney, and occasionally liver malignancies, and also the bone marrow, lymph nodes, and organs of the hematological system. So that, it's rare to find a malignancy in a child that has not some reflection in the blood. True, the sarcomas of the bone, and occasionally diseases of the lung and of the pancreas or stomach will not develop much anemia. But since in childhood they usually interfere with appetite and interfere with growth and development, anemia is very common early symptom of a malignancy. Therefore pediatric hematologists have to know a fair amount of malignant disease diagnosis. And treatment too, because much of the treatment that you use for malignancy will affect the blood. Much more in childhood than in adult life, and you've got to be prepared to treat hemolytic and anemic conditions due to malnutrition, as well as treat the malignant disease itself. There hasn't been that split, therefore, amongst pediatricians and oncologists and hematologists, as there is at the adult level. In fact there's resistance to the idea of having separate boards of oncology in pediatrics, and hematology. We have hematology-oncology combination, and men and women that wanted to qualify for certificates in this specialty take an examination that includes both. In contrast to adults.
Q: Dr. Diamond, at this time I was wondering if you could comment on the various awards and honors that have been accorded you over the years. Could we please start with the 1946 awarding of the Mead Johnson award of the American Academy of Pediatrics?
Diamond: The American Academy of Pediatrics was given the privilege, or the duty, of suggesting to the Mead Johnson food company the recipient of two rewards given every year. The two are given at the time of the pediatric meetings, which were called the Mead Johnson awards. In 1946 I received a Mead Johnson award for the development of exchange transfusion, and the recognition and care of the newborn infant -- or the fetus -- with hemolytic disease of the newborn due to the RH factor. Of course it's now found to be due to other factors, but less commonly. The next one in 1959 is a gold medal from the Netherlands Red Cross, an award of merit given by them. I helped established the Red Cross blood transfusion center in Amsterdam -- which is now a tremendous transfusion and research center for research in protein, in blood components -- and in establishing blood banks all through the Netherlands and through some of the colonies as well.
Q: In 1963, you were given the Karl Landsteiner--
Diamond: In 1963 the Karl Landsteiner Award, which is given every year by the American Association of Blood Banks. This, too, was for the research work on the various blood factors -- the RH and others. Then in 1964, the Theodore Roosevelt Society, established in New York City in the old Roosevelt home down on East 22nd Street gave a golden medal for public service in science. I was given that in 1964. In 1966, the Joseph P. Kennedy award made by the Joseph P. Kennedy Foundation established by the Kennedy family in honor of the son that they lost in the war, for work in the prevention of brain damage. Our work on prevention of Kernicterus, a complication of severe jaundice in newborn, was recognized by this Foundation. In 1974, the American Society of Clinical Pathologists gave me the Philip Levine Award for work in hematology or in some pathology subspecialty for our work in blood group antibodies.
The American Medical Association gives an award through its pediatric section, which they call the Abraham Jacoby Award. Abraham Jacoby was the first recognized pediatrician who specialized in pediatrics, chiefly, back in the late 1800s --1890 or something. The Abraham Jacoby Award was given to us for our hematology research in general, and the rescue of children with iron deficiency and other anemia. In 1977, the United Cerebral Palsy Foundation gave me the award they call the Goldenson Weinstein Award, some money given by these two to establish an award for work that has a beneficial influence on cerebral palsy. In 1977-1978, I received an opportunity to go to the Center for Advanced Study in the Behavioral Sciences at Stanford to work on several articles for books. This is an award given to people who apply for the opportunity to study for a year at this center, where they are supported while they are doing nothing but work on books, articles, or something of that sort. That was a great year. I wrote up these two articles that were published in Wintrobe's book on blood. In 1980, the California Perinatal Association, interested in anything that helps the newborn baby, or even during pregnancy--the perinatal period -- gave me their annual award. As a matter of fact it was established at that time -- I received the first one of these rewards. Then finally in 1981, the Virginia Apgar Award, which is named after the obstetrician and anesthesiologist--great anesthesiologist--Virginia Apgar of New York. An award given by the Academy of Pediatrics-Perinatal Section for anything that is done to help in the care of newborns or babies before they're born.
So, that's the list.
Q: Okay. I wish to thank you Dr. Diamond, for this interview.
Diamond: You're very welcome. Thank you!
End of interview.