Biographical Memoirs Volume 45 (1974) / Chapter Skim
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George Richards Minot
George Richards Minot
Pages 353-401
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From page 354... ...
James Jackson, the second Hersey Professor and a cofounder with John Collins Warren of the Massachusetts General Hospital, which opened its doors in 1821. Thus his forebears, like those of other Boston medical families, were influential participants in the activities of the Harvard Medical School and its affiliated teaching hospital.
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From page 355... ...
This educational technique, employed earlier in the Harvard Law School, had been proposed by Cannon 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.
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From page 356... ...
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 wheelchair 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.
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From page 357... ...
This was the man who had discovered that blood platelets 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 microscopic examination of peripheral blood films stained by the use of the aniline dyes introduced by Ehrlich.
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From page 358... ...
From these observations they concluded, understandably but erroneously, that the platelets 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.
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From page 359... ...
In clinical instances of low levels of platelets associated with normal production of red cells and leukocytes, he suggested that excessive destruction 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.
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From page 360... ...
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)
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From page 361... ...
Huntington Memorial Hospital, where he had been appointed Assistant Consulting Physician in 1917 and Consulting Physician in 1919. Meanwhile, another essay in industrial medicine disclosed interesting changes in the blood of workers in an artificial silk factory.
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From page 362... ...
At the Huntington, Minot's clinical and research contributions were highly valued by his colleagues and by the Cancer 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.
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From page 363... ...
It was shortly before this time that Dr. Minot began to urge his private patients with pernicious anemia to improve their diets.
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From page 364... ...
Thus the findings in the peripheral blood, which were suggestive of diminished production of red cells, presented a puzzling contrast to the jaundice, increased iron deposits in liver and bone marrow, and large fecal excretion of bile pigments that were regarded as characteristic of increased red cell destruction. Indeed, in 1916 Minot and Sellards had demonstrated that, in pernicious anemia, an endogenous hemolytic process presumably interfered with the similar catabolism of experimentally injected hemoglobin.
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From page 365... ...
Frieda Robscheit-Robbins, had evolved a reliable protocol for experiments with dogs whose hemoglobin concentration in the circulating blood was kept at about half the normal value by bleeding at regular and frequent intervals. By 1923 they had demonstrated that this chronic anemia provided a strong stimulus to hemoglobin regeneration by the animal's bone marrow to which, however, the marrow was unable to respond significantly unless supplements such as liver, pork muscle, or spinach were added to the basal diet.
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From page 366... ...
It was not until 1932 that workers in Minot's laboratory showed in patients with iron deficiency anemia, often due to chronic blood loss as in Whipple's dogs, that when soluble iron was given parenterally it was quantitatively utilized in the production of new hemoglobin. Whipple confirmed this finding with intravenous injections in his experimental dogs, and thereafter he and his associates wrote yet another new chapter in experimental hematology by introducing the use of radioactive iron to the study of anemia.
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From page 367... ...
The clinical improvement in these patients became regular and impressive, especially in one of them who really enjoyed eating liver and did so with enthusiasm. Eventually, on May 4, 1926, Minot and Murphy reported their observations on forty-five patients to the Association of American Physicians, noting that the condition of all "became much better rather rapidly, soon after commencing the diet." Although admitting that these consistent improvements in health in their own series of cases "may not last longer than those of others," they felt it wise to urge pernicious anemia BIOGRAPHICAL MEMOIRS
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From page 368... ...
That the significance of an orderly augmentation of these young forms as an index of enhanced red cell production by the bone marrow was well known to Minot as early as 1916 has already been mentioned. Moreover, in 1923 Minot and Sampson had refuted the claim that germanium dioxide was a useful remedy for anemia by showing that it lacked ability to cause reticulocyte responses in experimental animals or in man.
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From page 369... ...
Cohn, who was Professor of Physical Chemistry at the Harvard Medical School. It was agreed that Cohn would undertake chemical analysis of liver with respect to its therapeutic activity in pernicious anemia, guided by clinical responses to successive experimental fractions to be supplied by him for tests of efficacy by Minot in patients with untreated pernicious anemia.
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From page 370... ...
Happily for the treatment of patients, Cohn and his associates as early as 1928 had reduced the daily requirement from 300 grams of liver to about 12.5 grams of a yellow powder, the so-called "fraction G." that possessed consistent activity in the treatment of pernicious anemia. In order that this experimental liver extract could be produced in quantity by a commercial process and submitted to clinical trial, a Committee on Pernicious Anemia of the Harvard Medical School was established.
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From page 371... ...
This amount was stated on the label of each manufacturer's product. In this way the benefit of Minot and Murphy's discovery became reliably available to the medical profession long before the isolation of the active principle of liver, vitamin Bit, in 1948.
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From page 372... ...
The feeding of half a pound of beef liver a day was successful in treating pernicious anemia because the concentration of the vitamin in that animal organ was great enough to allow passive assimilation by patients lacking the special mechanism normally involved in the absorption of the low concentration of vitamin BE in the usual diet. In 1928, following the tragic early death of his friend and colleague, Francis Peabody, Minot, already internationally famous, was appointed Professor of Medicine at Harvard and succeeded Peabody as the second Director of the Thorndike Memorial Laboratory of the Boston City Hospital and Chief of the Fourth (Harvard)
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From page 373... ...
With the production of experimental liver fractions well under way in Cohn's laboratory and their clinical evaluation in patients proceeding in the Harvard-affiliated Boston hospitals, Minot and his young pupils turned their attention to the study of the patients with so-called hypochromic anemia. In these patients, in contrast to those with pernicious anemia, the red corpuscles in the blood are pale and deficient in hemoglobin.
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From page 374... ...
Two years later, in the Thorndike Ward, Strauss confirmed this supposition under controlled nutritional conditions by showing that a well-balanced diet, supplemented with components of the vitamin B complex, resulted in improvement of the neuritis of patients "allowed to continue their customary daily intake of spirituous liquor." This was certainly clinical investigation with the informed and happy consent of the patients. As already mentioned, Minot as a young man had studied blood coagulation under Professor Howell in the Physiological Laboratory of the Johns Hopkins University School of Medicine.
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From page 375... ...
L Taylor, the biochemist of the Thorndike, played a prominent part, Minot and his associates prepared a so-called "globulin substance" from citrated cell-free normal plasma and showed it to have the effect of the parent platelet-free plasma in shortening the coagulation time of hemophilic blood both in vitro and when given intravenously.
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From page 376... ...
Blood films on glass slides often accompanied such inquiries. The characteristic care with which he composed his replies added to the burden of these "paper consultations." Alone, or with his associates, Minot contributed chapters on blood diseases to leading textbooks of medicine through several revisions.
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From page 377... ...
He saw that correction of these defects could be beneficial and, in teaching and published articles, advocated proper attention by physicians to what he called "social medicine." BIOGRAPHICAL MEMOIRS Despite the best of medical care, Minot developed in his middle fifties some of the vascular and neurological complications of diabetes. Informal conferences with close associates in his hospital office often took place while he was changing his socks and warming his feet dangerously close to an electric sun bowl near his desk.
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From page 378... ...
Richard Stetson, a young colleague and friend, who with his wife accompanied the Minots and their two adolescent daughters. Among foreign honors that came to Minot were honorary fellowships of the Royal College of Physicians, Edinburgh; the Royal College of Physicians, London; the Royal Society of Medicine, London; and a corresponding membership in the Royal Academy of Medicine, Belgium.
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From page 379... ...
His scientific work was implemented by his genius for taking infinite pains, and its relevance to clinical medicine changed the study of diseases of the blood from a largely descriptive to a dynamic subject that ever since has attracted productive basic and clinical investigation. In the area of nutritional anemias alone, the work of Minot and his pupils provided insight into matters not previously suspected to exist.
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From page 380... ...
In 1948, at the time of Minot's resignation, more than four hundred young doctors had served in the Harvard Medical Unit, either as resident physicians on its medical services or as research fellows in the Thorndike. In 1956 almost fifty of these held professorships in medicine, pediatrics, preventive medicine, or in a preclinical department of medical schools in the United States.
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From page 381... ...
. culturally an aristocrat, he was in behavior a democrat." His obituary in the Transactions of the Association of American Physicians for 1950 reads in part as follows: "Doctor Minot was a character in the best New England sense of that expression.
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From page 382... ...
Huntington Me morial Hospital Physician to Special Clinic, Massachusetts General Hos pital Special Consultant in Diseases of the Blood, Massachu setts General Hospital Associate in Medicine, Peter Bent Brigham Hospital Clinical Professor of Medicine, Harvard Medical School Member Board of Consultation, Massachusetts General Hospital Chief, Fourth Medical Service, Boston City Hospital Director, Thorndike Memorial Laboratory, Boston City Hospital Visiting Physician, Boston City Hospital 1928-1950 Professor of Medicine, Harvard Medical School Consulting Physician, Peter Bent Brigham Hospital
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From page 383... ...
Honorary Member, Royal Academy of Medicine (Belgium) Academy of Medicine of France 1935 1936 1938 1939 1945 Fellow 1912 1928 1935 Honorary Fellow 1931 Royal College of Physicians, Edinburgh 1932 Royal Society of Medicine, London American Medical Association American College of Physicians American Philosophical Society
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From page 384... ...
Moxon Medal, Royal College of Physicians, London John Scott Medal of City of Philadelphia Nobel Prize in Physiology or Medicine, jointly with William Parry Murphy and George Hoyt Whipple, for "discoveries respecting liver therapy in anaemias" Gold Medal of Humane Society of Massachusetts Scroll Award of Associated Grocery Manufacturers of America Gordon Wilson Lecturer and Medalist, American Clinical and Climatological Association Distinguished Service Medal, American Medical Asso.
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From page 385... ...
Journal of Clinical Investigation T
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From page 386... ...
Lee and Beth Vincent. Splenectomy in pernicious anemia: studies on bone marrow stimulation.
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From page 387... ...
Gray under supervision; the anemias; hemorrhagic diseases and conditions; transfusion of blood. In: The Nelson Loose Leaf Living Medicine, Vol.
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From page 388... ...
Erythremia (polycythemia rubra vera) : the development of anemia; the relation to leukemia; consideration of the basal metabolism, blood formation and destruction and fragility of the red cells.
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From page 389... ...
Buckman. The blood platelets in the leukemias.
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From page 390... ...
The Alumnae Journal, 7:1 7-1 9. Peter Bent Brigham Hospital, Boston, Mass.
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From page 391... ...
Lawson. Treatment of pernicious anemia with liver extract: effects upon the production of immature and mature red blood cells.
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From page 392... ...
With Raphael Isaacs. Pernicious anemia: synopsis of literature from North America during 1928.
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From page 393... ...
Am., 15: 797-804. Idiopathic hypochromic anemia.
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From page 394... ...
Bile pigment and hemoglobin regeneration: the effect of bile pigment in cases of chronic hypochromic anemia.
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From page 395... ...
Clinical investigation: physician and patient. (The Ninth Alpha Omega Alpha Annual Lecture)
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From page 396... ...
Some aspects of the anemias of nutritional deficiency. Journal of the American Dietetic Association, 12:522-26.
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From page 397... ...
Anemias of nutritional deficiency. In: A Symposium on the Blood Forming Organs, pp.
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From page 398... ...
Introduction to chapter- on hemorrhagic diseases and conditions. In: Nelson Loose Leaf Living Med icine, Vol.
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From page 399... ...
Heath. Differentiation of pernicious anemia and certain other macrocytic anemias by the distribution of red blood cell diameters.
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From page 400... ...
Transactions 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)
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