ASH Oral History: Louis K. Diamond (7/7)
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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.
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