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GEORGE RICHARDS MINOT December 2, 1885-February 25, 1950 BY W. B. CASTLE GEORGE MINOT was born in Boston, Massachusetts, on Decem- ber 2, 1885, the eldest of three sons of Dr. James Jackson and Elizabeth Frances (Whitney) Minot. His ancestors had been successful in business and professional careers in Boston. His father was a private practitioner and for many years a clinical teacher of medicine as a member of the staff of the Massachusetts General Hospital. In the second half of the nineteenth century his great uncle, Francis Minot, became the third Hersey Pro- fessor of the Theory and Practice of Physic at Harvard; and his cousin, Charles Sedgwick Minot, a distinguished anatomist, was Professor of Histology there in the early years of the twentieth century. George Minot's grandmother was the daughter of Dr. James Jackson, the second Hersey Professor and a cofounder with John Collins Warren of the Massachusetts General Hos- pital, which opened its doors in 1821. Thus his forebears, like those of other Boston medical families, were influential par- ticipants in the activities of the Harvard Medical School and its affiliated teaching hospital. George was regarded by his physician-father as a delicate child who required physical protection and nourishing food. Brief vacation visits to Florida provided escape, thought de- sirable for him, from the rigors of Boston winters. Most of a winter spent with his parents in southern California gave 337

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338 BIOGRAPHICAL MEMOIRS further opportunity for outdoor life and amateur studies of butterflies. This led to the publication in 1902 of his first scientific paper, an early expression of his lifelong interest in natural history. George Minot's early education was at private schools in Boston in the "Back Bay" near the home in which he grew up. As a matter of course he went on to Harvard College, from which he was graduated in the spring of 1908. After a summer in Europe, despite anxiety about his physical capacity for the busy life of a doctor, he enrolled in the Harvard Medical School armed merely with the documentation that his college courses had included physics and chemistry. During the summers of his second and third years in medical school Minot worked in an outpatient clinic operated by the faculty at the medical school for the benefit of employees and neighborhood residents. During his third year he achieved modest renown by demonstrating to the satisfaction of the medical staff of the Massachusetts General Hospital that a patient considered to have pernicious anemia was in reality suffering from a congenital hemolytic anemia. Among his teachers at the medical school were Walter B. Cannon in physi- ology, Otto Folin and Lawrence J. Henderson in biochemistry, Theobald Smith in comparative pathology, Richard C. Cabot and Henry A. Christian in medicine, and Maurice B. Richard- son in surgery. Christian's systematic lecture presentations of medical topics were admirably balanced by Cabot's novel "case teaching" exercises, in which students in their clinical years participated actively. This educational technique, employed earlier in the Harvard Law School, had been proposed by Can- non when he was a senior medical student at Harvard. It was during Minot's final year that he first showed a serious interest in hematology by enrolling in an elective course in clinical pathology given at the medical school by Dr. J. Homer Wright, inventor of the well-known polychrome stain for blood films. A few months after graduation young Dr. Minot began a

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GEORGE RICHARDS MINOT 339 coveted appointment as medical "House Pupil," as the interns at the Massachusetts General Hospital were then called. There, while working on the East Medical Service under Dr. David Edsall, the recently appointed Jackson Professor of Clinical Medicine at Harvard, he displayed increasing interest in diseases of the blood. For some reason, perhaps the familial insistence on the importance to health of good food, he began taking meticulous histories of the dietary habits of his anemic patients. He also exhibited an active interest in the laboratory findings, especially in the microscopic examination of stained films of their blood. Sixteen months later, at the end of November 1913, Minot completed his tour of duty as "Senior" and was borne in traditional fashion to the front door of the hospital in a wheel- chair propelled by his "Junior." Among recent graduates of the medical services he was in good intellectual company with such future distinguished physicians as James Howard Means and Paul Dudley White. Like them he was advised by Dr. Edsall to go elsewhere for further training before returning to the Massachusetts General Hospital with the prospect of becoming a junior member of its staff. It was soon arranged that Minot should go to Johns Hopkins and serve as Resident Physician under Dr. William S. Thayer, to whom Minot's special interest in patients with hematological problems soon became apparent. Consequently, after a few months Minot transferred his activities to the laboratory of William H. Howell, Professor of Physiology, whose principal research interest was in the coagulation of the blood. With an- other young physician from Boston, George Denny, Minot pub- lished in 1915 an article demonstrating that circulatory stasis during perfusion of the liver of the dog produced an increase in the antithrombin content of the blood in the hepatic vein. This insight, together with studies by others of his pupils, led three years later to Howell's successful preparation from liver of the valuable anticoagulant drug, heparin. Minot's other

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340 BIOGRAPHICAL MEMOIRS work, on the prothrombin and antithrombin factors involved in the abnormal clotting of the blood of various patients, would be interpreted somewhat differently today. However, oxalated blood samples from jaundiced patients with bleeding tendencies were observed to show abnormal delay in coagulation after re- calcification. This Minot and Denny correctly attributed to a diminished level of prothrombin as then defined. When Minot returned to Boston, in January 1915, he received appointments in the Harvard Medical School and in the Massa- chusetts General Hospital as Assistant in Medicine with a small stipend as a Dalton Scholar. In June he married Marian Linzee Weld in the Unitarian church in Milton, Massachusetts. At the hospital, Edsall's influence had brought to Boston the new era of scientific investigation of disease already begun in Baltimore and New York. In addition to participation in the care of patients Minot, as well as James H. Means and Paul D. White, who had returned from their studies abroad, and shortly Walter W. Palmer and James L. Gamble were attempting to apply scientific methodology to bedside medicine with the help of various types of simple equipment in improvised laboratories. This atmosphere of young inquiry was highly appropriate for Minot, who had an inherent faith in causality that made him optimistic that scientific understanding would lead to a bright future for clinical medicine. He found a bench with north lighting suitable for microscopic work in a small room next to the inner sanctum of the hospital's irascible pathologist, Dr. Wright. This was the man who had discovered that blood plate- lets were formed by large specialized cells in the bone marrow. At that time the study of the blood of patients with anemia, leukemia, low platelet levels, and other abnormalities depended largely on the enumeration of the corpuscles and the micro- scopic examination of peripheral blood films stained by the use of the aniline dyes introduced by Ehrlich. This permitted recognition under the oil immersion lens of morphological

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GEORGE RICHARDS MINOT 341 abnormalities of the blood's three formed elements: red cells, white cells, and platelets. In hematology the only useful drug, was iron, but a recent therapeutic advance was the transfusion of fresh blood. This, owing to the work of Landsteiner, Moss, and others in enabling the identification of suitable donors, had become a relatively safe, though technically demanding procedure. In the fall of 1915 Minot began work with Dr. Roger I. Lee, Clinical Professor of Medicine at Harvard and Chief of the West Medical Service at the Massachusetts General, in an at- tempt to learn more about the function of blood platelets insignificant particles, but already thought to be intimately involved in hemostasis and blood coagulation. After meticulous washing in physiological saline, a suspension of normal platelets derived from blood samples rendered incoagulable by addition of oxalate was found by Lee and Minot to be seventy-five times as efficacious as a similarly prepared suspension of hemophilic platelets in shortenings, the prolonged clotting time of fresh hemophilic blood plasma. This last was derived by centrifuga- tion of fresh blood in chilled, paraffin-coated tubes. Thus - encouraged, the two physicians gave a transfusion of normal blood to a hemophilia patient and found that it caused a prompt reduction of the patient's prolonged blood clotting time. The effect lasted for three days, an interval then considered to cor- respond to the life-span of the platelet. From these observations they concluded, understandably but erroneously, that the plate- lets in hemophilia were defective. This interpretation, because of the impossibility of completely freeing platelets from a subtle plasma factor, was only corrected thirty years later when work in ~Minot's laboratory at the Boston City Hospital showed that platelet-free, citrated, normal blood plasma could shorten the coagulation time of hemophilic blood owing to the presence of a specific globulin. From the Massachusetts General Hospital Minot published

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342 BIOGRAPHICAL MEMOIRS papers describing and classifying patients with anemia and markedly reduced numbers of blood platelets. He pointed out that a faltering bone marrow, in addition to producing too few new red cells, was often unable to sustain a normal number of circulating granular leukocytes and platelets. In clinical in- stances of low levels of platelets associated with normal produc- tion of red cells and leukocytes, he suggested that excessive de- struction of platelets was responsible. He speculated that the great increase in platelets sometimes following splenectomy was due to enhanced production by an uninhibited bone marrow. Although today the role of the spleen as combined pool and filter in causing low platelet levels is better understood, the mechanism of the sometimes prolonged increase in numbers of platelets after surgical removal of the spleen is not. In an ex- tensive study in 1916 of a young girl with idiopathic purpura hemorrhagica, who eventually bled to death because of her low level of blood platelets, Minot sought without success for evidence of platelet-agglutinating or -lysing properties in her serum. Even today these are detected only with great difficulty and only in some of such patients. In other work, with Dr. Wright, Minot studied the plasma factors involved in the so- called viscous metamorphosis of platelets, a step preliminary to their participation in normal blood-clot formation. While in Baltimore in 1914 Minot had studied the effect of splenectomy in a patient with pernicious anemia, then almost invariably a fatal disease although for some months subject to apparently spontaneous remissions and discouraging unex- plained relapses. The result of removal of the spleen in the patient had been temporarily favorable. Three years later in Boston Minot joined Lee and Beth Vincent, a surgical colleague, in studies of fifteen such patients skillfully subjected to sple- nectomy as a last resort. In some of these patients the results were beneficial for a few weeks or months, but they failed to be of a permanent value in any. However, Minot's careful ob-

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GEORGE RICHARDS MINOT 343 servations of the peripheral blood were of great significance to his future work on the successful dietary treatment of pernicious anemia. Wright had shown NIinot a method of supravital stain- ing that the latter applied to the demonstration of reticulocytes in films of the peripheral blood of these anemic patients. That reticulocytes were newly formed red cells released by the bone marrow, rather than degenerating forms as originally supposed by Ehrlich, had first been demonstrated by Theobald Smith in 1891 in bleeding experiments with Texas cattle. Vogel and McCurdy in 1913 had proposed that anemias could be classified as being due either to increased blood destruction or blood loss with an active marrow response (increased reticulocytes) or being due to bone marrow inadequacies of various sorts (de- creased reticulocytes). Now, Minot stated that in pernicious anemia "curves plotted from frequent observations tof the number of reticulated red cells] are reliable indicators of bone marrow activity and fincreases] are the forerunners of increased red cell counts and clinical improvement." When during World War I Base Hospital No. 6, organized by the Massachusetts General Hospital, sailed from New York for overseas duty, the work of the hospital staff of doctors and nurses left behind was greatly increased. Minot was directly involved with this extra burden of patient care as well as with his laboratory research and private practice. In addition, he was employed for a short time as Contract Surgeon by the army in examining recruits. He soon found much more interesting contributions to make to the war effort. At the suggestion of Dr. Alice Hamilton, then the only woman on the Harvard Medical Faculty and already an authority in industrial medicine, the army asked Minot to investigate the anemia of New Jersey ammunition workers engaged in filling shells with trinitro- toluene. He discovered the coexistence of methemoglobin and signs of a red cell-destroying process. A similar investigation concerned with manufacture of smokeless powder disclosed

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344 BIOGRAPHICAL MEMOIRS little but the anesthetic effects of various degrees of exposure to the ethyl ether used as a solvent. In the fall of 1918 Minot was involved in a desperate effort to prevent the spread of influenza among the students of Harvard College, many of whom were candidates for the Student Army Training Corps. Then in another month the epidemic waned, and the Armistice was signed. After the war Minot continued to study patients with blood diseases at the Massachusetts General Hospital, but with in- creasing involvement in work at the Collis P. Huntington Memorial Hospital, where he had been appointed Assistant Consulting Physician in 1917 and Consulting Physician in 1919. Meanwhile, another essay in industrial medicine dis- closed interesting changes in the blood of workers in an artificial silk factory. This led to a report in 1921 that an increase in the large mononuclear cells of the blood was a clear signal of liver damage to come, if exposure to tetrachlorethanethe volatile solvent inhaledwas not discontinued. The results of an at- tempt with Dr. Chester M. Jones to establish as a clinical entity the sporadic cases of infectious jaundice that appeared subse- quent to the epidemics of World War I was published in 1923. Here, too, immature and abnormal lymphocytes and mononu- clear cells appeared in the blood and resembled those seen in cases of so-called glandular fever or infectious mononucleosis. Indeed, at the time no serological test was available to dis- criminate glandular fever from infectious jaundice with cer- tainty. From the time of his first appointment at the Huntington Hospital Minot found himself becoming evermore interested in the special purposes of this "cancer hospital." Supervised by the Cancer Commission of Harvard University, composed of six distinguished physicians with Ernest E. Tyzzer as Director, the hospital had opened in 1912 for the purpose of providing what would be called today a "clinical research facility" where,

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GEORGE RICHARDS MINOT 345 in addition to the latest diagnostic and therapeutic modalities for the care of patients, basic research in the nature and cause of cancer and neoplastic blood disease could be conducted. Located close by the Harvard Medical School and the new Peter Bent Brigham Hospital, the Huntington Hospital was in no sense an institution merely for custodial care. Minot saw in this hospital setting a rare opportunity to extend his interest into new areas of blood disease with possible valuable repercus- sions on what he already knew. Moreover, in accepting the original appointment he was attracted by the delightful per- sonality, broad clinical and research experience, and scholarly wisdom of the hospital's Consulting Physician, Dr. Francis W. Peabody. At the Huntington, Minot's clinical and research con- tributions were highly valued by his colleagues and by the Can- cer Commission. When Peabody became Director of the new Thorndike Memorial Laboratory at the Boston City Hospital, in 1923, Minot was appointed to succeed him as Chief of the Medical Service at the Huntington. At the cancer hospital Minot became impressed with a relationship between polycythemia Vera, a disease producing too many red blood corpuscles, and myelogenous leukemia, a form of cancer of the blood in which too many abnormal white cells are formed. With his associates, Drs. Thomas E. Buckman and Raphael Isaacs, he published careful descriptions of the blood findings, clinical course, and results of x-ray treatment in myelogenous and other varieties of chronic leukemia. He con- cludedas is still true today, with modern x-ray and chemo- therapythat the benefits of treatment were chiefly to extend the period of reasonably good health, rather than to prolong the life of the patient. In another classical paper, in 1924, Minot and Dr. lloy G. Spurling described the different durations of the effects of x-ray treatment on the formed elements of the blood of patients with localized cancer, including the value of the number of circulating white corpuscles as an indication of the

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346 . ~ BIOGRAPHICAL MEMOIRS amount of such radiation that could safely be applied. It was shortly before this time that Dr. Minot began to urge his private patients with pernicious anemia to improve their diets. Meanwhile, a serious change in Minot's health and personal life had taken place. In October 1921, after noting for some days feelings of fatigue, weakness, and thirst, he tested his urine and found sugar. The next day Dr. Elliott P. Joslin confirmed the fact that at the age of thirty-six Minot had developed severe diabetes, for which the treatment was currently a form of semi- starvation. In those dark days Minot's cousin and medical school classmate, Dr. Francis M. Rackemann, and his wife gave cheer- ful support and wise counsel to the Minot family. The discovery of insulin by Banting and Best, announced in 1922, came in the nick of time to save Minot's life. After a year of dietary restric- tion and weight loss, during which Minot managed to struggle each day to the hospital, Dr. Joslin was able to secure for his patient small amounts of insulin. For the rest of his life Minot ate no food at home that was not weighed or measured and recorded. When dining out, advance knowledge of the menu aided him in estimating calories and carbohydrates. His wife, a charming and intelligent woman, was indispensible in sustain- ing the strict balance of dietary intake and insulin injections prescribed by Dr. Joslin. Under these circumstances, it was a distinct advantage to Minot to be able to continue his private practice as a member of the small group of physicians that he had joined at the invita- tion of Dr. Edwin A. Locke in September 1921, shortly before the onset of his diabetes. This arrangement provided office space at 31 1 Beacon Street, with shared secretarial services and a laboratory with a technician trained to perform the usual simple studies of patients' blood and urine. Included in the group was a succession of younger physicians who in this way were entering the practice of medicine in Boston. Among them was Dr. Wil- liam P. Murphy, who later was asked by Minot to be his col-

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374 BIOGRAPHICAL MEMOIRS meet.) Chapter XVI. In: The Oxford Medicine, ed. by Henry A. Christian, Vol. 2, pp. 646-72. New York, Oxford University Press. With William P. Murphy, Edwin l. Cohn, Richard P. Stetson and Herman A. Lawson. The feeding of whole liver or an effective fraction in pernicious anemia: the response of the reticulocytes. Trans. Assoc. Am. Physicians, 42:81-86. With William P. Murphy. Treatment of pernicious (Addisonian) anaemia with a diet rich in liver. Brit. Med. i., 2:674-76. The treatment of pernicious anemia with liver on an effective frac- tion of liver. (The Mary Scott Newbold Lecture XVIII) Trans- actions of the College of Physicians of Philadelphia, 49: 144-53. 1928 A familial hemorrhagic condition associated with prolongation of the bleeding time. Am. i. Med. Sci., 175:301-6. With Edwin l. Cohn, Gordon A. Alles and William T. Salter. The nature of the material in liver effective in pernicious anemia. II. l. Biol. Chem., 77:325-58. With William P. Murphy and Richard P. Stetson. The response of the reticulocytes to liver therapy; particularly in pernicious anemia. Am. l. Med. Sci., 175:581-99. With Edwin i. Cohn, William P. Murphy and Herman A. Lawson. Treatment of pernicious anemia with liver extract: effects upon the production of immature and mature red blood cells. Am. I. Med. Sci., 175:599-622. The treatment of pernicious anemia. In: The Harvey Lectures, 23: 151-53. Baltimore, Williams & Wilkins Company. (Synopsis) With William P. Murphy and Edwin J. Cohn. Le traitement de l'anemie pernicieuse par un regime riche en foie ou par un extrait de foie. Annales de Medecine, 23:319-27. 1929 A non-fatal case simulating acute leukemia with anemia and thrombopenic purpura. Med. Clin. N. Am., 13:1-9. Recent progress: treatment of pernicious anemia. In: Nelson Loose Leaf Living Medicine, Vol. 4, pp. 59A-H. New York, Thomas Nelson Sc Sons. Some fundamental clinical aspects of deficiencies. Ann. Internal Med., 3:216-29.

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GEORGE RICHARDS MINOT 375 Presentation of the Kober Medal to George R. Minot, M.D., for research in scientific medicine: remarks by George R. Minot, M.D. Trans. Assoc. Am. Physicians, 44:11-12. Treatment of pernicious anemia. In: The George Blumer Edition of Billings and Fo~rchheimer's Therapeusis of Internal Diseases, Suppl., pp. 423-34. New York, D. Appleton & Company. Treatment of anemia, other than pernicious anemia, with diet. In: The George Blumer Ed ition of Billings and Fo~rchheimer's Therapeusis of Internal Diseases, Suppl., pp. 435~2. New York, D. Appleton & Company. With Edwin I. Cohn and Thomas L. McMeekin. The nature of the material effective in pernicious anemia. III. Am. I. Physiol., 90: 316-17. (A) 1930 With Janet M. Vaughan and Gulli Lindh Muller. The response obtained in healthy pigeons by the administration of substances effective in pernicious anaemia. Lancet, 218: 1062; also in J. Clin. Invest., 9: 3-4. (A) With Edwin l. Cohn and Thomas L. McMeekin. The nature of the substance effective in pernicious anemia. Trans. Assoc. Am. Physicians, 45:343-49. With Edwin l. Cohn and Thomas L. McMeekin. the material effective in pernicious anemia. IV. The nature of J. Biol. Chem., 87:49-52. The treatment of pernicious anemia and the importance of an optimal diet for man. journal of the National Institute of Social Sciences, 15: 28-32. With Stacy R. Mettier and Wilmot C. Townsend. Scurvy in adults: especially the effect of food rich in vitamin C on blood formation. J. Am. Med. Assoc., 95:1089-93. With Raphael Isaacs. Pernicious anemia: synopsis of literature from North America during 1928. Folia Haematologica, 41: 179-88. 1931 With Henry Jackson, Jr. The medical care of the cancer patient. American journal of Cancer, 15: 6-11. With Stacy R. Mettier. The effect of iron on blood formation as influenced by changing the acidity of the gastroduodenal con- tents in certain cases of anemia. Am. l. Med. Sci., 181:25-36.

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376 BIOGRAPHICAL MEMOIRS The treatment of anemia. New Engl. J. Med., 204:1104-5. (A) Review of A Brief History of Medicine in Massachusetts by Henry R. Viets. Boston and New York, Houghton Mifflin Company, 1930. In: New England Quarterly 4: 362-65. With William B. Castle. The adequate treatment of anemia. Ann. Internal Med., 5:159-69. With Clark W. Heath. The response of the reticulocytes to iron and some aspects of iron therapy. Trans. Assoc. Am. Physicians, 46:290-95. The treatment of anemia: with comments on food deficiency and its relation to the nervous system. Transactions of the American Neurological Association, 57: 329-32. 1932 With Clark W. Heath. The response of the reticulocytes to iron. Am. J. Med. Sci., 133:110-21. Chronic arthritis: remarks concerning prevention and treatment. Med. Clin. N. Am., 15: 797-804. Idiopathic hypochromic anemia. In: Emanuel Libman Anni- versary Volumes, Vol. 2, pp. 831-45. New York, International ~ ress. The importance of the treatment of pernicious anemia on a quanti- tative basis. Trans. Am. Clin. Climat. Assoc., 48:31-38; also in J. Am. Med Assoc., 99: 1906-8. 1933 Three cases of chronic dietary deficiency: features are chronic fatigue, anemia and prolonged coagulation time of the blood. Med. Clin. N. Am., 16:761-71. With Soma Weiss. Nutrition in relation to arteriosclerosis. In: Arteriosclerosis: A Survey of the Problem, pp. 233-48. Publica- tion of the Josiah Macy, Jr., Foundation. New York, The Macmillan Company. James Jackson, 1812-1836. Harvard Med. Alumni Bull., 7(Jan.~: 25-29. James Jackson as a professor of medicine. New Engl. J. Med., 208: 254-58. Deficiency disease from lack of specific gastric reaction: the etiology of pernicious and related macrocytic anemias. (Editorial) New Engl. J. Med. 208: 556-57. , . . . .

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GEORGE RICHARDS MINOT fames Jackson and alcoholic neuritis: a correction. Alumni Bull., 7(April):54-55. William Sidney Thayer. Harvard Med. Alumni Bull., 7 (April): 55-56. With Maurice B. Strauss and Stanley Cobb. "Alcoholic" poly- neuritis: dietary deficiency as a factor in its production. New Engl. J. Med., 208:1244-49. General aspects of the treatment of chronic arthritis. New Engl. I. Med., 208: 1285-90. President's address: The importance of art and the general principles of treatment in chronic arthritis. Trans. Am. Clin. Climat. Assoc., 49:50-58; also in I. Am. Med. Assoc., 101:1266. (A) With Thomas E. Buckman. Chapters on purpura, hemorrhagic disease of the newborn and hemophilia (revised). In: A Text Book of Medicine, ed. by Russell L. Cecil, 3d ea., pp. 1043-~. Philadelphia, W. B. Saunders Company. Chapter on erythremia (revised). In: A Text Book of Medicine, ed. by Russell L. Cecil, 3d ea., pp. 1055-59. Philadelphia, W. B. Saunders Company. 377 Harvard Med. 1934 Anemia: etiology and treatment. (First Jessie Horton Kessler Lec- ture) Proceedings of the Institute of Medicine of Chicago, 10: 2-~. Thoughts concerning the teaching of medical social conditions. journal of the Association of American Medical Colleges, 9: 147-49. Medical social aspects in practice. Arch. Internal Med., 54:1-10. With Arthur I. Patek, fir. Bile pigment and hemoglobin regenera- tion: the effect of bile pigment in cases of chronic hypochromic anemia. Am. I. Med. Sci., 188:206-15; also in I. Clin. Invest., 13:717. (A) The interpretation of reticulocyte responses in pernicious anemia. Trans. Assoc. Am. Physicians, 49:287-98. Nutrition in relation to mental disorders. In: The Problem of Mental Disorder, a study by the Committee on Psychiatric In- vestigations, National Research Council, pp. 255-65. New York, McGraw-Hill Book Company, Inc. Animal experimentation: its importance and value to scientific

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378 BIOGRAPHICAL MEMOIRS medicine. Bulletin of the American College of Surgeons, 18: 17-18. The clinical investigative laboratory. In: Lilly Research Labora- tories Dedication, pp. 42-45. Indianapolis, Indiana. Some aspects of anaemia. Medical reporter's notes of lecture to the Royal Society of Medicine, London. Lancet, 227: 1281-83. 1935 Some aspects of the diagnosis of pernicious anemia. Am., 18:935~4. Med. Clin. N. The development of liver therapy in pernicious anaemia: a Nobel lecture delivered before the Caroline Institute at Stockholm, December 12, 1934. Lancet, 1:361-64; also in Les Prix Nobel en 1934, pp. 1-10. Stockholm, P. A. Norstedt & Soner. Remarks at dinner of Nobel Foundation, December 10, 1934. In; Les Prix Nobel en 1934, pp. 58-59. Stockholm, P. A. Norstedt & Soner. With William B. Castle. The interpretation of reticulocyte re- actions: their value in determining the potency of therapeutic materials, especially in pernicious anaemia. Lancet, 2:319-30. Clinical investigation: physician and patient. (The Ninth Alpha Omega Alpha Annual Lecture) J. Am. Med. Assoc., 105:641-45. The anemias of nutritional deficiency; etiology, diagnosis, treatment and prevention. l. Am. Med. Assoc., 105:1176-79. 1936 With William B. Castle. Pathological physiology and clinical description of the anemias. Chapter XVI in: The Oxford Med- icine, ed. by Henry A. Christian, Vol. 2, pp. 589-680. Also re- printed as book, Pathological Physiology and Clinical Description of the Anemias. New York, The Oxford University Press. Pernicious anaemia: the latest word on the etiology and treatment of pernicious anaemia-by a Nobel prize-winner. In: The World Today, Vol. 3, pp. 11-13. Chicago, Encyclopaedia Britannica, Inc. Foreword. Instruction of medical students in the social aspects of medicine. Bull. Am. Assoc. Med. Social Workers, 9:34. Purpura hemorrhagica with lymphocytosis: an acute type and an intermittent menstrual type. Am. i. Med. Sci., 192:445-56. Discussion of talk by Arlie V. Bock, "The use and abuse of blood transfusions." New Engl. i. Med., 215: 425. -

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GEORGE RICHARDS MINOT 379 Anemia and the gastro-intestinal tract: a synopsis. American ~our- nal of Digestive Diseases and Nutrition, 3:643-46. Harvard and nutrition. New Engl. l- Med., 215:1147-49. 1937 .. .. Manniskan Ar Vad Hon Ater: Framtidens Medicin (Medicine and the Future). Svenska Dagbladet (Stockholm, Sweden>, p. 5, ~anu- ary 10; reprinted in Olosta Gator; Actuella Problem. Svenska Dagbladets Naturvetenskapliga Enquete 1937, pp. 179-81. Stock- holm, Wahlstrom & Widstrand. Some aspects of the anemias of nutritional deficiency. Journal of the American Dietetic Association, 12:522-26. Investigation and teaching in the field of the social component of medicine. Bull. Am. Assoc. Med. Social Workers, 10:9-18; re- printed in Anniversary volume: Scientific Contributions in Honor of Joseph Hersey Pratt on His Sixty-ltifth Birthday, pp. 940-51. Lancaster, Pennsylvania, Lancaster Press. Discussion of paper by M. At. Wintrobe, E. M. Hanrahan and Caroline Bedell Thomas, "Purpura hemorrhagica with special reference to course and treatment." l. Am. Med. Assoc., 109: 1176. Notes concernant les troubles du sang. Bulletin et memoires de la societe de medecine de Paris, 141:800-801. Chapter on pernicious anemia (revised). In: A Text Book of Med- icine, ed. by Russell L. Cecil, 4th ea., pp. 996-1004. Philadel- phia, W. B. Saunders Company. With Thomas E. 13uckman. Chapters on purpura, hemorrhagic disease of the newborn and hemophilia (revised). In: A Text Book of Medicine, ed. by Russell L. Cecil, 4th ed. pp. 1025-37. Philadelphia, W. B. Saunders Company. Chapter on erythremia (revised). In: A Text Book of Medicine, ed. by Russell L. Cecil, 4th ea., pp. 1037~1. Philadelphia, W. B. Saunders Company. 1938 Discussion of paper by C. P. Rhoads and W. Halsey Barker, "Re- fractory anemia: analysis of 100 cases." l. Am. Med. Assoc., 1 10:795. Progress on anaemia. In: Britannica Book of the Year, 1938, p. 43. Chicago, Encyclopaedia Britannica, Inc.

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380 BIOGRAPHICAL MEMOIRS With Clark W. Heath, Frederick I. Pohle and Gunnar Alsted. The influence of mucin upon the absorption of iron in hypochromic anemia. Am. l. Med. Sci., 195:281-86. The President's address. Trans. Assoc. Am. Physicians, 53:1-6. Nutritional deficiency. Ann. Internal Med., 12:429-42. Foreword to Medicine in the Out-Patient Department, by Winthrop Wetherbee, Jr. New York, Paul B. Hoeber, Inc. Clinical Investigation. Science, 88:413-16; also in The Diplomate, 1 1 :48-52 (1 939~; J. Am. Med. Assoc., 1 1 2: 1 2 10-1 3 (1939~ . (A) The etiology, diagnosis and treatment of the anemias of nutritional deficiency. Bulletin of the New England Medical Center, 1:4-5. (Synopsis) Discussion of paper by Claude E. Forkner, "An attempt to consoli- date and to clarify present views concerning the anemias and the hemorrhagic disorders." In: Abstracts of the Proceedings of the Forty-ninth Annual Meeting of the Life Insurance Medical Di- rectors of America, Vol. 25, pp. 279-81. Printed for private cir- culation, New York City, Press of Recording and Statistical Corporation. Doctor a day: liver extract treatment in pernicious anemia. Pub- lished under auspices of the Massachusetts Medical Society and the Massachusetts Department of Health. Boston Evening Transcript, February 5, p. 13. Discussion of paper by Frank H. Krusen, "Physical therapy in arthritis." New Engl. J. Med., 220:469-70. The activities of the Children's Hospital. Harvard Med. Alumni Bull., 14:9-12. Anemias of nutritional deficiency. In: A Symposium on the Blood Forming Organs, pp. 52-56. Madison, University of Wisconsin Press. (A) 1940 Anemias of nutritional deficiency. (The Gordon Wilson Lecture) Trans. Am. Clin. Climat. Assoc., 55:175-80. Chapter on pernicious anemia (revised). In: A Text Book of Medi- cine, ed. by Russell L. Cecil, 5th ea., pp. 1076-85. Philadel- phia, W. B. Saunders Company. Chapters on purpura, hemorrhagic disease of the newborn, hemo- philia and erythremia (revised). In: A Text Book of Medicine, ed. by Russell L. Cecil, Sth ea., pp. 1111-26. Philadelphia, W. B. Saunders Company.

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GEORGE RICHARDS MINOT 1941 381 Foreword to Chinese Lessons to Western Medicine: A Contribution to Geographical Medicine from the Clinic of Peiping Union Medical College, by I. Snapper. New York, Interscience Pub- lishers, Inc. 1942 Soma Weiss. In: In Memoriam, Soma Weiss, 1899-1942, pp. 14-19. Peter Bent Brigham Hospital, Boston, Mass. (Remarks at a memorial ceremony in honor of Soma Weiss, held March 19, 1942) With E. P. Jordan and others. Primer on arthritis. Prepared by a committee of the American Rheumatism Association. I. Am. Med. Assoc., 119:1089-1104. Some problems of nutritional deficiencies. nomics. 34:477-78 Rest. Journal of Home Eco- , . . . 1942 Proceedings of the Interstate Postgraduate Medical As- sembly of North America, pp. 207-8. 1943 The problem of nutritional deficiencies. Chapter III in: The Role of Nutritional Deficiency in Nervous and Mental Disease. Re- search Publications of the Association for Nervous and Mental Disease, 22:29-32. Baltimore. Williams & Wilkins ComnanY. (AN With Maurice B. Strauss. Physiology of anti-pernicious anemia material. Vitamins and Hormones, 1:269-91. Chapters on pernicious anemia, purpura, hemorrhagic disease of the newborn, hemophilia and erythremia (revised). In: A Tex t Book of Medicine, ed. by Russell L. Cecil, 6th ea., pp. 970-90. Philadelphia, W. B. Saunders Company. Introduction to chapter- on hemorrhagic diseases and conditions. In: Nelson Loose Leaf Living Med icine, Vol. 4, p. 103. New York, Thomas Nelson & Sons. With F. H. L Taylor and Charles S. Davison. Chapter L. The physiology of blood coagulation. In: Nelson Loose Leaf Living Medicine, Vol. 4, pp. 105-115D. New York, Thomas Nelson & Sons. 1944 Foreword to Atlas of the Blood in Children, by Kenneth D. Black- fan and Louis K. Diamond. New York, Commonwealth Fund.

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382 BIOGRAPHICAL MEMOIRS 1945 Review of Atlas of the Blood in Children, by Kenneth D. Blackfan and Louis K. Diamond. New York, Commonwealth Fund. In: Harvard Med. Alumni Bull., 19:101. With F. H. L. Taylor, C. S. Davidson, H. I. Tagnon, M. A. Adams and A. H. MacDonald. Studies in blood coagulation: the coagulation properties of certain globulin fractions of normal human plasma in vitro. J. Clin. Invest., 24:698-703. With C. S. Davidson, Jessica H. Lewis, H. l. Tagnon and F. H. L. Taylor. The coagulation defect in hemophilia: the effect, in hemophilia, of the parenterol administration of a fraction of the plasma globulins rich in fibrinogen. i. Clin. Invest., 24:704-7. 1946 Foreword to first issue of B lood, The Journal of Hematology. Blood, 1:1-2. With Geneva A. Daland and Clark W. Heath. Differentiation of pernicious anemia and certain other macrocytic anemias by the distribution of red blood cell diameters. Blood, 1:67-75. With Jessica H. Lewis, Henry J. Tagnon, Charles S. Davidson and F. H. L. Taylor. The relation of certain fractions of the plasma globulins to the coagulation defect in hemophilia. Blood, 1: 166-72. With Jessica H. Lewis, C. S. Davidson, i. P. Soulier, H. l. Tagnon and F. H. L. Taylor. Chemical, clinical and immunological studies on the products of human plasma fractionation. XXXII. The coagulation defect in hemophilia: an in vitro and in vivo comparison of normal and hemophilic whole blood, plasma and derived plasma protein fractions. I. Clin. Invest., 25:870-75. With C. S. Davidson, Jessica H. Lewis, l. P. Soulier, H. l. Tagnon and F. H. L. Taylor. Les proteines plasmatiques et le probleme de l'htmophilie. Le Sang, 17:293-302. David Linn Edsall, 1869-1945. 9-10. With M. B. Strauss. Fisiologia do principle antipernicioso. Re- sehna clin.-cient., 15: 101-12. Trans. Assoc. Am. Physicians, 59: 1947 With F. H. L. Taylor. Hemophilia: the clinical use of antihemo- philic globulin. Ann. Internal Med., 26:363-67.

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G E O R G E R I C H A R D S M I N O T 383 The hospital a look ahead: some aspects of clinical investigation. New Engl. J. Med., 236:563-66. The diagnosis and treatment of the macrocytic anemias. Trans- actions and Studies of the College of Physicians of Philadelphia, 15: 1-6. Chapters on pernicious anemia, purpura, hemorrhagic disease of the newborn, hemophilia and erythremia (revised). In: A Text Book of Medicine, ed. lay Russell L. Cecil, 7th ea., pp. 1091- 1111. Philadelphia, W. B. Saunders Company. Nutrition and health. Nutrition Reviews, 5:321-22. Pernicious anemia. In: American People's Encyclopedia, 1:858-62. New York, Grolier, Inc. 1948 The modern management of macrocytic anaemias. Brit. Med. l., 2: 153-54.

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