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This oral history is one in a series of interviews conducted by the Columbia University Oral History Research Office in the late 1980s to early 1990s documenting the history of ASH and the development of the profession of hematology in the United States. Columbia University holds the copyright to this oral history, and anyone interested in quoting this transcript must first contact the University for permission.
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 one tape-recorded interview with Dr. William Bosworth Castle, conducted by Dr. David Nathan on May 27, 1987, in Cambridge, Massachusetts. Dr. Castle has reviewed the transcript and made corrections and emendations. In 2007, Dr. Castle's son, William Rogers Castle, 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.
May 27, 1987
Q: Dr. Castle, could you tell me a little bit about your family background?
Castle: Well, my father, William Ernest Castle, who lived from 1867 to 1962, was Professor of Zoology at Harvard and a pioneer in experimental mammalian genetics at the turn of the century. [See L. C. Dunn Biographical Memoirs, National Academy of Sciences, 38; 33-80, 1965.] My mother, Clara Sears Bosworth, 1870-1940, was the daughter of a farmer living near Wellsville, Kansas, whose wife insisted strongly on college education for their children. Clara graduated from the University of Kansas at Lawrence and married my father in 1886. In later years, her considerable talents led to the production of amateur plays and interesting accounts of early life in Kansas. In 1897, I became the first born of three sons: William; Henry, who died while in his second year of Harvard College; and Edward, subsequently Professor of Physiology at Harvard College.
I was born at 10 Ash Street Place in Cambridge, Massachusetts, in one of a few single-family houses with backyards situated on one side of that quiet non-thoroughfare. Its other side bordered the lawns and gardens of the Greenleaf Estate. A good place for a child to learn to respect the prior rights of tolerant gardener Murphy and his floral borders.
In 1907, the family, now of five, moved to a newly built house at 186 Payson Road, Belmont, Massachusetts. Our dwelling had no near neighbors and overlooked a quarter mile away the extensive market gardens, orchards, and greenhouses of the Hittinger Farm. With the friendly young Hittinger boy as our playmate, this offered the untutored learning experiences of a running brook, a shallow former ice pond, a barn, a blacksmith shop and, once only, a paper wasp's nest. My father now exhibited the knacks and talents of the farm boy that he had been by grafting hit trees and cultivating a kitchen garden bordered by phlox and iris. Unlike his youngest son, Edward, in adolescence, I was little interested in my father's attention-demanding animal breeding experiments, as I grew up, or in his agricultural enjoyments.
When in 1909 his animal work was transferred from Cambridge to Harvard's Bussey Institute, in another Boston suburb, Forest Hills, a tedious daily commuting trip became a necessity of his academic life. Salvation came with the purchase of a 1915 Model T Ford as suggested by Walter B. Cannon. This was not without its perils, as he was a slow learner at the wheel.
I was at once interested in the machine and its planetary transmission and being young required no more than a few hundred yards of open road to learn how to drive and shortly to make elementary repairs. After two or three secondhand Model Ts of my own in college and medical school, I purchased a Ford Model A Roadster, the only factory-new car that I have ever owned. It achieved fame with medical students and hospital house staffs and was loaned to at least two research fellows for their honeymoon travels.
In 1933, I married Louise Griffin Muller, a lovely public school music teacher from a suburb of Philadelphia, whose good nature and common sense have often put me in mind of "the lady from Philadelphia" of The Peterkin Papers. She had graduated from West Chester State College in 1929 and after our marriage in 1933 we lived in Brookline, Massachusetts. There she became, through membership in the League of Women Voters, interested in local public affairs and in 1960 was elected to the town's Board of Selectmen. The first woman to achieve such membership in Brookline, she served for nine years.
Q: Dr. Castle, what about your early education? Can you tell me something about how you first made any contact with science teaching in secondary school and in undergraduate levels?
Castle: In 1909, my father entered me in Browne and Nichols preparatory school in Cambridge. Our teachers were now all men who presided in their own rooms to which we went when the bell rang. I learned ungladly the required Latin and English and elective French. Also, regrettably, a year of Greek rather than German. Plane geometry seemed a labored effort to prove the obvious but algebra allowed the solution of practical problems when once clearly set forth. I yearned for a final fourth year when I could learn elementary physics by simple classroom experiments. With classmate Tom Cabot, I engaged in and survived after-school experiments with fuming acids, electric arcs and gunpowder in his home. And with Russell Cogswell, tried to understand the working principles of wireless telegraphy and the practical construction of a simple crystal receiving set. I could never learn to read Morse code.
Q: Then how did medicine become a career choice?
Castle: I entered Harvard College early in the month after the distant "Guns of August" were heard in 1914 and for the first time lived away from home in Gore Hall, one of President [A. Lawrence] Lowell's new freshman dormitories on the Charles. Meeting and making new friends from other schools and other states was heady stuff. Night-time bull sessions that I think explored the subject freely rather than merely scored debater's points were intellectually rewarding, at least to me. I took courses in chemistry, biology, and physics, including an elective on the nature of matter at a subatomic level by Theodore Lyman. Lectures by Professor [Elmer] Kohler on inorganic chemistry were often related to industrial use, but I first heard of and saw the periodic table of the elements in his course. Far from its present completeness, it gave exciting evidence of a fundamental order in the universe. The experiments of Jacques Loeb with plants and animals seemed to obey the same laws. The human politics of the World War was a shocking contrast. During parts of summer vacations, I took demanding month-long courses: surveying at the Harvard Engineering Camp on Squam Lake and quantitative inorganic chemistry in Professor Theodore W. Richards' laboratory. The problem assigned was to determine the atomic weight of sodium, a meticulous exercise for me in how not to spill salt in the process. I also worked in a shipyard in Bath, Maine, helping to build Liberty Ships and spent July 1917 in Officers' Training Camp in Plattsburg, NY.
I decided upon a medical career as a result of educational experiences in Harvard College that showed me that I was not bright enough to be a physicist or biologist and that success in most professions leads to a desk job with domination of or by others. It seemed to me that this was not necessarily so for a career in medicine, where, for example, in contrast to law nature, not man, is the adversary. Indeed, I saw that if a doctor wished, he could remain always and usefully in direct contact with the object of his endeavors, the sick man, woman, or child. Moreover, three of my closest college friends were planning to go to medical school: Tracy Mallory, Grantley Taylor, and Howard Sprague.
It was easy to get into Harvard Medical School in 1917 after three years in Harvard College. More doctors were expected to be needed for the war in Europe. Many faculty members were already in military service in hospital units or as special consultants, though most were released by the end of my second year. The curriculum was the Flexnerian type [named for Abraham Flexner, who published an influential report on medical education in 1910]: two years of lectures on preclinical sciences with related student laboratory exercises and physical examinations mainly of normal heart and lungs. Then a third year of lectures on clinical subjects relieved by occasional CPC's by Richard Cabot himself. He had elsewhere expressed the opinion, unpopular with the general medical profession, that there were only twelve drugs with therapeutically demonstrable efficacy. In the final fourth year came the clinical clerkships in medicine and surgery at the major teaching hospitals and the opportunity to complete the required dozen obstetrical deliveries on the district (slums) of Boston. This was described by Fritz [Frederick C.] Irving, Professor of Obstetrics at the time, in the "The Ballad of Chambers Street."
In retrospect an extracurricular event was for me of special interest. This was the Cutter Lectures given at the medical school in the fall of 1917 by the young Dr. E.V. McCollum of Johns Hopkins. He described the growth requirement for small amounts of a "water-soluble B" and a "fat-soluble A" substance by young rats kept on simplified diets. Restoration of normal growth was promptly achieved when minuscule amounts of A or B were provided. Thinking of the striking cure of oriental beriberi by restoring the husks to a diet of polished rice held out prospects for discovery and relief of other human disorders by a "newer knowledge of nutrition." At the moment, finding a medical internship if possible in Boston seemed of more importance.
Q: Dr. Castle, can you tell me a little about what the internship was like at the Mass. General Hospital when you went there?
Castle: The 21-month medical internship was a progressive experience divided into seven three-month periods. First was outpatient medicine--neurology or dermatology--under supervision of part-time practitioners. Then a period of simple laboratory procedures on blood, sputum, or urine of individual ward patients. Next a period of collecting blood and other samples for examination by other hospital department laboratories such as bacteriology, biochemistry, or pathology. At long last with one's arrival at the level of junior house physician, one began to share in the work-up and care of ward patients and often to attend morning ward rounds with the residing physician of the month. Progressively from there on one assumed more responsibility in the management of patients with the limited therapeutic means available--few drugs, bed rest, and excellent nursing care. Skill was acquired in the succinct presentation of individual patients to idiosyncratic members of the visiting staff who made rounds for an hour or so in the mornings of weekdays. They were also available for after-hour consultation by the senior house staff when necessary as were members of the visiting staffs of surgical or other services. We interns were also aware of the informal research activities of one or two recent graduates of the internship who had small laboratories in the basement of the Bulfinch building. Arlie [V.] Bock was there too, carrying out experiments for L. J. Henderson on the fitness of the physical chemistry of the blood.
Q: Did you get an interest in hematology during your internship and residency or did that occur after you went to the School of Public Health? By the way, you were there for two years--can you tell me a little bit about that School of Public Health experience?
Castle: There was no residency available to me at the MGH and the normal course of life for a medical intern graduate was to go into an apprenticeship with an older physician, or if academically inclined, to find an appointment in a preclinical department of a medical school. My interest in hematology had been aroused by contacts with Dr. George Minot while I was in medical school, but in the fall of 1921 he developed diabetes and struggled bravely to continue limited medical work with dietary management little short of starvation. In January of 1923 Dr. Eliot Joslin was able to obtain small amounts of insulin for him, and Minot's life was extended to1950.
My appointment in the Harvard School of Public Health was simply because the academic appointment and laboratories of Dr. Cecil Drinker were there. In Dr. Walter Cannon's absence in Europe, he was acting head of Physiology in the medical school. I had in my first year of medical school undertaken some student research under Drinker's guidance and now in 1923 was fortunate to receive an appointment as Assistant in his department. What I did there was to work with Dr. Harold Himwich, who had come from Yale School of Medicine well-grounded in metabolic medical science. Harold was interested in the finding of certain European physiologists that the unitary respiratory quotient of excised muscle, both amphibian and mammalian, indicated that only carbohydrate was oxidized. With my help in preparing an isolated self-perfused gastrocnemius muscle in living decerebrate dogs, we were able to show that the average respiratory quotient of the resting muscle was not 1.0 but rather 0.71 or close to that of the expired air of the dogs. Like the whole animal, it was using both carbohydrate and fat as a source of energy.
This experience taught me that experimental work requires strong motivation, long hours, and hard work. It also convinced me that I preferred to study patients, if possible, in a scientific mode in a hospital setting. And so when near the end of a second year I was invited to consider an appointment under Francis Peabody at the recently-opened Thorndike Memorial Laboratory at the Boston City Hospital, I gratefully accepted. At that juncture I told Dr. Walter Cannon, who had returned from abroad to head the physiology department in the Harvard Medical School, as was proper, that I was to go to the City Hospital that fall. He remarked, "Ah, another brand for the burning." That is a metaphor of which I have been unable since to find the meaning, but have concluded that it was not congratulatory.
Q: So you went off to be "burned" at the Thorndike. Can you tell me a little about those early days under Peabody? What the Thorndike was like as an experience? How did it function?
Castle: The importance of the Thorndike opened in 1923 was that it contained a comfortable ward for the study under controlled conditions of patients selected from the medical services. Thus it was surrounded by the rest of a large municipal hospital with a wide variety of patients. Those chosen for study in the Thorndike were being cared for by young men who were much interested in their work and did not forget that the patient was the valued object of their scientific and humanitarian concern. Thus there was opportunity for concentrated research effort provided by the Thorndike ward and its closely affiliated biochemical, hematological, and physiological laboratories all, in the same building. There was also a small animal house on the roof.
Soma Weiss, strongly recommended by his medical chief, Dr. Eugene Dubois of Cornell's New York Hospital, came to the Thorndike at the same time that I did in September 1925. Already appointed in 1923 were three Assistants to Dr. Peabody: Henry Jackson, Jr., Robert N. Nye and Joseph T. Wearn and a research assistant, a lady physician graduate of Columbia P and S, Dr. G.L. Muller. In 1924 Drs. Herrman Blumgart, Charles A. Doan and Perrin H. Long joined the Thorndike staff and Dr. Peabody became Chief of the Harvard (Fourth) Medical Service. There he and a mature Back Bay practitioner, Dr. Edwin A. Locke, together presented to the house staff a fine example of the integration of medical science with the care of the patient. Francis Peabody believed strongly that ward teaching experience was vital in the training of the Thorndike staff.
Q: Dr. Castle, did you immediately meet Dr. Minot when you came to the Thorndike and did you start working on the problem of pernicious anemia right away?
Castle: Dr. Peabody was the director of the Thorndike until his untimely death in 1927. Dr. Minot did not come to the Thorndike until 1928, but as a medical student I had already met him at the Massachusetts General Hospital. In my second year in medical school, I failed to pass the course in laboratory medicine partly because, I like to think, I honestly reported my inability to make the two areas of the counting chamber for red cells come out within the then required limits. Anyhow, I was asked by Dean Worth Hale to take a makeup examination which was supervised by Dr. Francis Peabody. He kept away from such technical matters and asked me questions about mechanisms of anemia, which I found not only interesting to try to answer, but educational. I also heard in medical school that it was known, especially from the work of Levine and Ladd at the Bringham Hospital and from the work of Arthur Hurst in London, that in pernicious anemia the stomach invariably lacks the normal ability to secrete hydrochloric acid. Also, that there is a neurological disorder that goes along with some cases of pernicious anemia. It seemed to me that--
Q: Excuse me Dr. Castle, the Levine you're talking about-- is that Samuel A. Levine?
Castle: Yes, Samuel A. Levine.
Q: Who became the famous cardiologist.
Castle: Later, at the City Hospital, I saw patients with scurvy and "alcoholic" polyneuritis, the latter considered by Dr. George Shattuck to possibly be related to oriental beriberi, a nutritional disorder due to lack of something present in the husks of unpolished rice. I hoped that there might be other opportunities for the discovery of reversible nutritional deficiencies in the clinic. When Minot and [William P.] Murphy demonstrated in 1926 that progress of an incurable disease, pernicious anemia, could be completely arrested by liver feeding, it suggested the possibility either of a metabolic disorder or of a nutritional deficiency. The problem was that there was nothing strikingly wrong with the diet of the patient with pernicious anemia, and that it was curious that it was necessary for pernicious anemia patients to eat liver but not for the normal individual. However, a simple connection seemed possible through the lack of digestion in the pernicious anemia stomach indicated by the consistent lack of hydrochloric acid, which from the work of [Arthur] Hurst was known sometimes long to precede the development of the anemia, and from a few surgical operations to follow total removal of the stomach. So it occurred to me that defective digestion of food of some sort in the stomach of the patient with pernicious anemia might deprive him of something that was present in liver. And that I attempted to prove.
Q: Dr. Castle, how did Minot's efforts tie into [George H.] Whipple's? What was the relationship, and was there some sort of community of scientist and clinicians communicating with one another on this kind of nutritional problem?
Castle: I think communication between scientific communities was something that didn't occur very often between practitioners of medicine and pre-clinical scientists. Whipple was head of the Department of Pathology at the new medical school in Rochester, NY. For several years he had been studying the quantitative relation of various food substances to hemoglobin regeneration in a colony of dogs subjected to repeated blood loss. Minot was a member of a group practice in Boston who had taught himself to count blood cells and to make accurate diagnoses from microscopic inspection of stained blood smears. He had a well-deserved reputation as a skilled hematologist and was the medical consultant of the Huntington Hospital, a small Harvard research institution. In 1925 Whipple and Robschsit-Robbins reported "the favorable influence of liver, heart and skeletal muscle" in their dogs. Liver was the most active. Minot and W.P. Murphy then decided to give it a try in 10 patients with pernicious anemia. By May 1926 200 grams a day had produced a prompt clinical improvement and sustained increases in red blood cells in more than 40 patients.
At the time the basis of the response of the patients as well as that of the dogs was not understood. Even the Nobel Committee, which should have known in 1934, when it awarded the prize to Whipple, Minot and Murphy, didn't realize that they were dealing with two entirely different conditions. They assumed, reasonably perhaps, that there was something in liver that was fundamental for bone marrow function and so stated. Since liver had been used by both Whipple and Minot with success, it seemed appropriate that they should both be given the award. So it was certainly the right award for the wrong reason. And unfortunately, some things happen like that in life.
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