Biographical Memoirs Volume 67 (1995) / Chapter Skim
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William B. Castle
William B. Castle
Pages 14-41
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From page 15... ...
in ensuing years Castle and associates characterizes} the red cell defects responsible for paroxysmal nocturnal hemogiobinuria and hereditary spherocytosis and established the role of heightened hemoglobin viscosity in the pathogenesis of sickle cell anemia. Castle once attributed his record of achievements to "being in the right place at the right time especially with the 15
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From page 16... ...
Examination of the abundant scientific and philosophical writings by and about William Ernest Castle provides uncanny prophecy of the forthcoming character of William Bosworth Castle. The unconventional views of the father, as recorded by L
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From page 17... ...
The overt purpose and simplicity of mechanics held a moral authority that conformer! with puritanical convictions instilled in his childhooct; these rejected the evils of adornment, fashion, and other forms of evasion or conceit.
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8 BIOGRAPHICAL MEMOIRS caller! in his 1986 autobiographical sketch, Castle first heard of and saw the periodic table of the elements in Professor KohIer's course on inorganic chemistry: Far from its present completeness it gave exciting evidence of a fundamental order of the Universe.
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From page 19... ...
Minot from dying in diabetic coma. With this dramatic example of the raw potential in medical research, Castle could not envision a life of rushing up brownstone stairs to attend to indisposed Boston merchants.
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Peabody granted the flunkee an opportunity to redeem himself via an interview, and CastIe's performance was sufficiently memorable to gain him an historic appointment. At this time Peabody was deeply interested in the cancer-like marrow morphology of pernicious anemia, and Castle assisted him in the collection of tibial marrow biopsy specimens obtained by surgeons employing mastoid trephines and cuvettes.
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From page 21... ...
S Ladd, that all pernicious anemia patients lack gastric juice, the trouble must be that deprived of effective digestion in their stomachs—they were unable to
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From page 22... ...
Hale Ham summed up experiments performed in sixty-one consecutive cases, and silenced critics of the Castle hypothesis, in a succinct synopsis of their long labors: If beef muscle and gastric juice are administered without opportunity for contact, they are not effective. It is obvious, therefore, that the activity of mixtures of beef muscle and gastric juice cannot be due to the simple addition of two subthreshold substances but requires an interaction between them.
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From page 23... ...
When he submitted his initial studies of intrinsic factor to the Warren Triennial Prize Committee at the MGH in 192S, Castle was bounc! by rules requiring anonymity.
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From page 24... ...
by his influence in the field of tropical diseases, Castle in 1931 enlisted the interest of the Rockefeller Foundation in underwriting an expedition to Puerto Rico to assess the efficacy of his liver extract in patients with tropical sprue. Under Rockefeller auspices, an entourage consisting of Castle, Cornelius P
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From page 25... ...
deep blue shoaled to bright green towards the yellow sand gently fingered by the moving shadows of palm fronds...."5 But there were also darker shallows and the hovering stench of sickness caused by tropical sprue, a dispiriting disease endemic to this island. Tropical sprue patients had megaloblastic anemia and severe giossitis similar to that of untreated pernicious anemia, but these patients failed to respond to oral liver extract or to combinations of beef muscle and normal gastric juice.
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From page 26... ...
When receiving the Kober Medal, Castle reminisced that he had been privileged to experience several great moments of insight and promise for the future. Foremost among these were the appearance of the first reticulocyte response in pernicious anemia to autodigested beef muscle, the dramatic improvement in tropical sprue inducecl by parenteral liver extract, and the startling increase in viscosity of deoxy
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From page 27... ...
and packing ("erythroconcentration") of red cells were primary mechanisms in many kinds of hemolytic anemias, including hereditary spherocytosis (HS)
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From page 28... ...
This led to Castle's famed postulation that the painful crisis, organ infarcts, and hemolytic anemia of sickle cell disease were the consequence of a vicious cycle initiated by increased viscosity, the endpoint being vascular occlusion by ensnarIed rigidified red cells. This 1940 interpretation of events at the cellular level took wing in 1945 during a legendary conversation between Castle and Linus Pauling, as they traveled together by overnight train from Denver to Chicago.
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From page 29... ...
Itano, and others began studies using moving boundary electrophoresis that showed sickle cell hemoglobin to be intrinsically abnormal in its electrophoretic migration. The reports of this finding ushered the age of molecular biology into clinical medicine.
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From page 30... ...
Progressively hampered by complications of diabetes, Minot had gradually transferred the reins of office to Castle during the 1940s, a process made official by Castle's appointment as director in 1948. Thorndike tradition had strongly nurtured a clo-it-yourself philosophy, often placing outrageous (remands on the vector, ana Castle ana nis chancellor of the exche~ 1 if_ ~ 1 1 ~ quer, Maxwell Finland, kept a keen watch on the number and quality of incoming fellows and the resources grudgingly allotted them.
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From page 31... ...
land} and co-workers already hacl launched a broad attack on the mechanisms of hemolytic anemias, bearing out many of the predictions made earlier by Ham and Castle, and then conducted increasingly independent stu(lies that among other things defined the role of Fc receptors in immune hemolysis and demonstrated the existence of transferrin receptors. With characteristic magnanimity, Castle transferred responsibility for the hematology division to {and]
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From page 32... ...
affiliate. As he had done at the Boston City Hospital, Castle soon imbued the staff of the West Roxbury V.A.
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From page 33... ...
, his astute comments and biological or philosophical excursions invariably added sparkle as well as insight. HIS LANGUAGE AND PHILOSOPHY CastIe's facility with words adcled immeasurably to the impact of his written and spoken thoughts, which nearly always contained one or more graceful phrases lastingly treasured in the memories of rapt listeners.
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From page 34... ...
After dropping handbills in my letterbox advertising $7 pants and $3 shirts, and then extolling the thrift of powdered milk as a solution available to the impecunious, Castle's final stratagem on one occasion was to send me a copy of a communication from Francis Peabody written in 1925. In this letter Castle was offered a stipend of $T,000 per year; on the margin he penned the words, "As are you, Tim, so once was I." Frugality and abhorrence of waste were ironed into his soul, but with the resources possessed by him his scientific instincts, his language skills, use of his aged cars, the summer house he and Louise made available to friends and fellows with these he was always generous.
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From page 35... ...
"I thought perhaps you were pondering the future directorship of the Thorndike! " After sweaty tasks of this kind, we generally cooled off in the river and then resumed discussions of how skunk cabbages melt their way through hard ice or other mysteries of nature that invited exploration.
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~ AM INDEBTED TO Elin and Richard Wolfe of the Countway Library, the late Lillian Blacker of the Harvard Medical Area News Office, and.~ohn W Harris of Case Western Reserve University for help in collecting source material.
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From page 37... ...
VIII. Molecular orientation in sickle cell hemoglobin solutions.
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From page 38... ...
I The effect of the administration to patients with pernicious anemia of beef muscle after incubation with normal human gastric juice.
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IX. Quantitative methods for determining the osmotic and mechanical fragility of red cells in the peripheral blood and splenic pulp; the mechanisms of increased hemolysis in hereditary spherocytosis (congenital hemolytic jaundice)
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From page 40... ...
I Observations on the sequestration and lysis of red cells altered by immune mechanisms.
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