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Biographical Memoirs: V.59 (1990)

Chapter: Maxwell Mayer Wintrobe

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Suggested Citation:"Maxwell Mayer Wintrobe." National Academy of Sciences. 1990. Biographical Memoirs: V.59. Washington, DC: The National Academies Press. doi: 10.17226/1652.
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MAXWELL MYER WINTROBE October27, 1901-December9, ·986 BY WILLIAM N. VALENTINE WHEN MAXWEEE MYER WINTROBE died in Salt Lake City on December 9, 1986, his distinguished career in med- icine and in his subspecialty of hematology had spanned some sixty years from the conquest of pernicious anemia to the present. His scientific achievements are recorded in more than 400 publications. His Clinical Hematology, first pub- lished in 1942 and currently in its eighth edition, remains a prototype of excellence and for many years stood alone as the premier text in his chosen field. In 1943 Max Wintrobe became the founding chairman of the Department of Medicine at the University of Utah—a post he filled with great energy and ability until 1967. From that time until his death he continued an active and produc- tive career at Utah as Distinguished Professor. By all accounts, Max was a world leader in hematology, a role attested to by a legion of honors, visiting professorships, memberships and activities in national and international scientific societies, consultantships, editorial responsibilities, and perhaps most importantly—by the large cadre of stu- dents who had flocked to be under his tutelage and who themselves went on to be leaders in their medical communi- ties and in academia. 447

448 BIOGRAPHICAL MEMOIRS EDUCATION AND EARLY LIFE Max Wintrobe was born October 27, 1901, in Halifax, Nova Scotia. His parents (both of whom hac! emigrated from Austria) adjusted rapidly to the new community, adding the English language to their repertoire of German, Polish, and Yiddish. Their educational background! was limited and their lifestyle frugal, as dictated by modest means. His mother's family, the Zwerlings, was large ant! had been in Canada for many years. Max, an only child, responded to his mother's deep interest in education and her urgings to stucly, work hard, ant! achieve. In 1912, the family moved to Winnipeg, Manitoba, where, however, there were few French and no family. A better-than-average student, Max entered the Univer- sity of Manitoba at age fifteen. Having already determines! on a medical career, he also made the decision to spend four undergraduate years before entering medical school, though only one year was required at the time. At the University he showed his facility for language, favoring English, Latin, and French ant! winning goIc! menials in the latter and in political economy. He also discovered his love of history and the well- turnec! phrase so important to his later career. Entering medical school at twenty, Max developed a spe- cial interest in the Johns Hopkins Medical Center through the writings of William Osler, but limited circumstances pre- vented any thought of transferring. Throughout his under- gracluate and medical school years he worked at a variety of ocict jobs to further his education ant! to help the family fi- nances. Of his teachers at Manitoba he remembered William Boyct, professor of pathology a flowery and exciting lec- turer with a rich Scottish brogue as the most stimulating. But as graduation neared, Max, who had achieved an out- standing record, became increasingly aware of his lack of

MAXWELL MYER WINTROBE 449 desire to go into private practice, though other opportunities were few and resources limited. After his internship and re- ceipt of the M.D. degree in 1926, the dilemma was resolved by the offer of the first Gordon Bell Fellowship, named in honor of the dean of the University who had just retired. Wintrobe was first assigned the task of determining the relative prevalence of achiorhyciria in certain western Cana- clian communities where the incidence of pernicious ane- mia a subject of especially great interest in 1926 was be- lieved to vary widely. A second assignment, pursued energetically but fruitlessly, was to produce achylia gastrica in clogs. Thus was launched a clistinguishecI, lifelong aca- demic career in the field of hematology. THE TULANE YEARS (1927—19304: ANEMIA OF THE SOUTH, NORMAL BLOOD VALUES, THE WINTROBE HEMATOCRIT, AND CORPUSCULAR CONSTANTS In September 1927, Max arrived in New OrIeans, having accepted the offer of an appointment as assistant in medicine at Tulane University from Dean C. Bass. Assures! of an an- nual stipend of $1,800 and a small laboratory next to Roy Turner—a Hopkins graduate ant! the consummate erudite clinician it was possible to get married. Max returned to Winnipeg and shortly thereafter, on January I, 192S, brought his bricle, nee Becky Zamphir, from the-50°F of Winnipeg to bright, sunny New OrIeans. Max's New OrIeans years were both pleasant and procluc- tive. Charity Hospital offerect a wealth of clinical material, inclucting nutritional ant! other anemias of all types, tropical disease, tuberculosis, and every variety of neoplasia. John H. Musser, the distinguished chief of medicine, suggested that Wintrobe find out if the widely believed "anemia of the South" myth actually existed. Though Max could not identify any such entity, the study allowed him to collect tiara and

450 BIOGRAPHICAL MEMOIRS develop techniques that became an integral part of the clin- ical evaluation of all patients, not only those with blooc! and marrow disorders. He first worked to document statistically normal values for hematologic parameters in normal adults and children. Acceptec! round numbers of normality at that time were cle- rivec} from only a few counts and from observations some seventy-five years old. A "normal" hemoglobin value in men was expressed as ~ 00%. Wintrobe's careful observations macle on Tulane medical students and women from Sophie Newcomb College together with observations by Russell Haclen in ClevelancI, Edwin Osgood in Portland, and a few made in Europe served as basic ciata for establishing nor- mality in terms of quantitatively accurate observations. Max's second important contribution was the invention of the Wintrobe hematocrit, which universally replacer! the leaky, awkwardly calibrated ant! poorly conceiver! devices of the 1920s. Wintrobe's calibrated, straight-sided tube helct about a milliliter of blood. Most importantly, any venous blood sample being measured in the tube was anticoagulated with a combination of potassium and ammonium oxalate that clid not cause cells to shrink or swell. Although many millions of the Wintrobe hematocrits have been soIci, neither Win- trobe nor Tulane profited. Since the instrument was intended for the public good, Wintrobe refused all royalties ant! ap- plied for no patent. Another important innovation came to Wintrobe in the mi(lclle of the night while puzzling over the inadequacies of the various indices then in vogue. These includec} color, vol- ume, and saturation indices derived indirectly from ratios based on "percent of normal" for reel cell numbers, hemo- gIobin content, etc. Wintrobe's methoc! permitted direct cal- culation of the average cell size, MCV (mean corpuscular vol- ume in cubic microns), MCH (mean hemoglobin content in

MAXWELL MYER WINTROBE 451 picograms), and MCHC (mean corpuscular hemoglobin con- centration in percent) quantifications that are stanclarct procedure in research and clinical laboratories today. I. H. Musser's invitation to assist him in rewriting the sec- tion on diseases of the blooc! for the ten-volume looseleaf set of the Tice Practice of Medicine (1931,3) marked a new step in Wintrobe's career. The new section was documented with great care and had a lengthy bibliography, not a common practice at the time. This desire for full bibliographical cloc- umentation later resulted in one of the most valuable features of Wintrobe's textbook Clinical Hematology ~ ~ 942,5~. During his three years in New OrIeans, Wintrobe worked toward his Ph.D. degree. His thesis, The Erythrocyte in Man (1930,3), represented a review of worIct literature and of his own studies in that fielcI. In his efforts to apply appropriate statistical methods to his own data, Wintrobe had contacted Raymond Pear] at Johns Hopkins, author of the helpful Introduction to Medical Biometry and Statistics. With the assistance of Dean Bass, Win- trobe was able to journey to Hopkins, see Pearl, and meet Alan Chesney, clean of the Medical School. When searching for a suitable publication for his thesis sometime later, Win- trobe hit upon the review journal Medicine; serendipitously, Chesney was its editor. Chance again favored Max, his thesis was publishecI, and his long-cherished wish to study an(1 work at Hopkins became a reality. He was offered an appointment as instructor in the Division of Clinical Microscopy. JOHNS HOPKINS ~ ~ 930—~ 943) The Wintrobes fount! some aspects of life in Baltimore less than pleasing, but meclically an(1 scientifically Hopkins was all they had hope(1 for. Max directed the second- and thircI-year courses in clinical microscopy, stimulating his stu- clents by integrating laboratory findings with clinical prob-

452 BIOGRAPHICAL MEMOIRS lems and diagnoses. In adclition he worker! in the Outpatient Department and gave consultations as requester! a practice that burgeoned as his reputation spread. The student caliber was good, the faculty talented and in the forefront of medicine. The times were busy but the Great Depression had brought austerity to all. Max had no secre- tarial assistance and there were no funcis to train technicians. He trained his own assistants (including Becky) but could pay them nothing. Instead, he bartered training for their ser- vices. To assist in studies in comparative hematology, Becky first mastered the art of venipuncture on fish, and she sub- sequently became chief technician at the diagnostic clinic. Max carried out studies of comparative hematology on animals in the Washington, D.C., Zoo, and during one en- joyable summer at Mountain Desert Island in Maine, where Homer Smith, Jim Shannon, and other distinguished scien- tists were also working. The Wintrobes spent other summers pleasantly working at Woods Hole in Massachusetts. Baltimore was the site of much intellectual exchange in medicine, and Wintrobe enjoyed and benefited! from discus- sions with his many colleagues, including George Minot, Bill Castle, and others of the Boston group. Max's career-Ion" interest in pernicious anemia, for instance, was furthered by his admiration of CastIe's classic experiments, and Castle ap- propriately authored the foreword to his last book, Hematol- ogy, the Blossoming of a Science ~ ~ 985, I ). It was also fitting that Irving Sherman, a Hopkins student working with Wintrobe, incidentally noted birefringence of sickles! red cells in the course of his studies on the role of deoxygenation in producing sickling. Bill Castle later brought this fincling to the attention of Linus Pauling in a chance conversation, giving birth to studies that wouIc] define the molecular lesion of hemoglobin responsible for sickle cell anemia and usher in the era of molecular biology.

MAXWELL MYER WINTROBE 453 In 1933 Becky and Max, backed by a six-month leave and a half-year's pay, embarked! on the first of their many trips to Europe. During these months they visited a large number of institutions and met many of the current and future leaders of hematology in Englancl and on the continent. Among many others were Otto Naegli of Zurich, acknowledged as the outstanding hematologist in Europe, Isidore Snapper, whose clinic was in HolIancI, Paul Morawitz of Leipzig, and Janet Vaughn of England. Although Max's first paper was published in 1928 in the New Orieans Medical and Surgical journal, by 1933 he had already achieved a considerable rep- utation in the field of hematology. At Hopkins he sought to expand his data on normal blood values and on the uses of the hematocrit. He clemonstrated that the hematocrit effectively measured erythrocyte secli- mentation rate and that, when proper centrifugation was em- ployed, the volume of packed red cells could be ascertained accurately and the mass of leukocytes and platelets roughly approximated. The supernatant plasma was also a conve- nient medium for determining icterus. With the hematocrit, Wintrobe was also able to demonstrate a cryogIobulin in blood and to diagnose a previously unsuspected case of mul- tiple myeloma. As he and Buell reporter} in the Bulletin of the fohns Hopkins Hospital (1933,2), the temperature dependent, reversible turbidity evident in supernatant plasma in a he- matocrit temporarily placed in a refrigerator, had led the researchers to this diagnosis. After returning from Europe, Max resumed a busy sched- ule of writing anc} research. In 1940 he published a study of forty members of three Italian families, some of whom suf- fered from splenomegaly, milct icterus, and blood changes recognized as a mild form of thalassemia. In a footnote he pointed out that the same condition had been observed in the parents of a patient with Cooley's anemia, also cited in a

454 BIOGRAPHICAL MEMOIRS later table in his first edition of Clinical Hematology. This ob- servation coincicled with independent observations by Da- meshek ant! Strauss in America and Silvestroni and Bianco, somewhat later, in Italy, to establish the recessive transmission of thalassemia. In 193S, another study by Wintrobe and Rob- ert H. Williams (later to head the Department of Medicine at the University of Washington in Seattle) clemonstratec! that nonautolyzed yeast in sufficient amounts could induce a he- mopoietic response in patients with pernicious anemia. As a house officer, Williams was able to sequester suitable subjects from the eye of Professor Longcope, who was unenthusiastic about the study. The hemopoietic response presumably arose from large amounts of folic acid in the yeast supplement. Other studies conducted with H. B. Schumacker, who later became chief of surgery at Indiana University, centerec! on the significance of macrocytosis and its association with liver disease. Struck by the fact that macrocytosis occurred in both human ant! animal fetal development, Max, his stu- dents, and coworkers began studying fetal Hood in experi- mental animals. The opossum prover! unaccommodating and was abandonecI, but the domestic pig proved more tract- able. Wintrobe's early work with this animal model provided a basis for his later studies in nutritional anemia, vitamin deficiency, ant! trace metal metabolism carrier! out at Utah. Though attempts to produce pernicious anemia in animals prover! fruitless, other studies brought about diverse scien- tific contributions in many areas: the role of splenectomy in thrombocytopenic purpura, the etiology and management of the anemias, and the diverse manifestations of the leukemias. Quantitatively cleterminec! corpuscular constants became universally accepted as a basis for classifying red cell ctis- orders. All of these investigations, both clinical and in the labo- ratory, follower! Max's moclus operands. Experiments were

MAXWELL MYER WINTROBE 455 clone meticulously, records were fully clocumented and main- tained, all available literature was explored thoroughly, and compendious bibliographies were compiled. Max consistently involved both students and house officers in his research ac- tivities, and his association with fine investigators (such as pathologist Arnold Rich) stimulated the flow of ideas while building valuable contacts. Many of these students and house officers later achieved fame, including George Eastman Cart- wright, who worker! with Max as a second-year student, fol- lowed him to Salt Lake City, and in 1967 succeeded him as Utah's chairman of medicine. On Pear] Harbor Day, December 7, 1941, Max was work- . sing to complete the index of the first edition of Clinical Hema- tology (1942,54. Since the authorities insisted he remain in Baltimore he began studying chemical warfare agents with Professor Longcope and Val Jaeger, then a house officer. At Utah, he and Jaeger later continued the work begun at Baltimore's U.S. Army Edgewoocl Arsenal (in Baltimore). In 1943, Max was called to be the chairman of Medicine at the newly established University of Utah Medical School—the first four-year medical school between Denver and the Pacific Coast from Canada to Mexico. T H E UTA H Y EA RS ~ ~ 94 3—~ 9 ~ 6 Max was now an established leader in hematology in charge of the Clinic for Nutritional, Gastrointestinal ant! Hemopoietic Disorders and an associate physician at Hop- kins. ClinicalHematoZogy, published in 1942, hac! filled a major voic! in the field and was well on its way to becoming the leacling hematological reference work. But when the Wintrobes and their young daughter, Susan Hope (born in Baltimore in 1937), considered moving to Utah in 1943, they did so with considerable trepidation. As Canadians, they knew little about Utah, but two Hopkins

456 BIOGRAPHICAL MEMOIRS men Phillip Price and A. Louis Dippel—were going there as, respectively, chief of Surgery and chief of Obstetrics- Gynecology at the new school. In adclition, Alan Gregg, vice-presiclent of the Rockefeller Foundation, and Isaiah Bowman, president of Johns Hopkins, both urgect Max to accept, stressing the importance of this opportunity to open ~ . a new frontier. But if Utah offered "opportunity," it offerecl, in Max's own fiord, "absolutely nothing more." The hospital's clinical facil- ities ant] plant were run clown and poorly administered. The medical school was hou sect in a dormitory co ns tructecl for World War ~ cavalry officers. The promised new medical cen- ter materialized only after twenty-two years, to be cledicatecl two years before Max's retirement as chief of medicine. In 1943, as far as he was concerned, faculty in all departments had to be recruited, medical care improved, student scholas- tic standards raised, goals reoriented, research projects and facilities established, and supporting funds obtained. Despite these hare} facts, all the departments continued to grow steaclily, and their chairmen functioned well together. By 1950, the Department of Medicine faculty numbered ten and included high-caliber, enthusiastic recruits dedicated to the goal of establishing a first-rate medical school. The Hematology Division enjoyed worIdwicle fame, attracting young physicians from North America and elsewhere in large numbers. Max instituted a program (later widely emulated) whereby students, house officers, and fellows initially exam- inec! all patients, whether private or nonpaying, as subjects for undergraduate and graduate teaching. Between 1947 and 1984, 170 graduate students were trained in hematology and participates! in research activities at Utah. Well over half remained in academic medicine, a number as leaders, ant!

MAXWELL MYER WINTROBE 457 several later shared authorship with Max in the seventh and eighth editions of Clinical Hematology. The National Institutes of Health first research grant went to the Utah study of muscular dystrophy and other he- reditary and metabolic disorclers. Encouraged to seek federal support by Senator Elbert Thomas of Utah, chairman of the Senate Committee on Health, Max had applied. Senator Thomas and U.S. Surgeon General Parran wantec! to con- tinue peacetime support of medical research, and the Utah senator was also an enthusiastic supporter of his state's new four-year school. The initial bill provicled $100,000 a year, which was subsequently renewed for twenty-three years, pro- victing the new school monies for faculty recruitment in many fields other than medicine. The grant supported work that wouIcl bring recognition and renown to the school ant! its stab. Muscular dystrophy of a hereditary type affected a considerable number of Utah families, ant! the Mormon reservoir of genealogical data was a substantial aid to research. Max served as director of the Laboratory of Hereditary ant! Metabolic Disorders from 1945 to 1973 and was succeeded by Frank Tyler, who had, from its inception, been head of its Clinical Division. Among Utah's more distinguished recruits was Emil Smith, who be- gan his important studies in biochemistry in shacks, all the research facilities then available. During the years when Max served as Utah's founding chairman of medicine he also became an international leacler in his chosen field, well beyond the University confines. He served as a visiting professor throughout the worIcl and re- ceive(1 honors and filled high positions too abundant to men- tion. His twenty-five years of participation in the work of the Research Grants Division of NIH began in 1949 and in- cludecl four years on the Council of the institute of Arthritis

458 BIOGRAPHICAL MEMOIRS and Metabolic Diseases, four years on the Allergy ant! Infec- tious Disease Council, and service on the Study Sections of Biochemistry and Hematology (including chairmanship of the latter) ant! on a variety of NTH committees with special charges. His many other responsibilities included consultantships to the Army, the Atomic Energy Commission, and the World Health Organization; chairmanship of the Advisory Com- mittee of the Leukemia Society; and nine years in various capacities with the American Medical Association's Council on Drugs. From 1964 to 1974, Max served as member and chairman of the Scientific Advisory Committee, Scripps Clinic and Re- search Foundation, La Volta. He was president of a large number of prestigious learned societies including the West- ern Association of Physicians, the Association of Professors of Medicine, the Association of American Physicians, and the American ant! International Societies of Hematology. He be- came a master of the American College of Physicians in 1973 and the same year received the Robert H. Williams Award of the Association of Professors of Medicine. In ~ 974, Cecil Wat- son presenter! him with the coveted Kober Mecial of the As- sociation of American Physicians. Elected to the National Academy of Sciences in 1973, he became the first chairman of the Section on Human Genetics, Hematology, and Oncol- ogy and, for three years, secretary of the Class on Medical Sciences. The Utah Group and the Wintrobe Legacy Despite this plethora of commitments, Max's hematology research program at Utah flourished and expanclecl. As his own involvement in national and international activities in- creasecI, G. E. Cartwright, then head of Hematology, as- sumed direction of the Research and Training Programs.

MAXWELL MYER WINTROBE 459 Yet if Max was less active in the laboratory, he continuer! to be involved with the University, particularly in the area of training. He also wrote more than two dozen papers on the pathogenesis of the anemia of infections—including studies of erythrocyte life span, marrow response, and the impaired return of iron from the macrophage to plasma. Extending Wintrobe's original Baltimore experiments with pigs (recorded in some seventeen papers), the Utah group established the pig as a mocle} experimental animal. They defined deficiencies of the vitamin B complex and neu- rologic lesions but were unable to produce pernicious anemia in the pig. They documented megaloblastic anemias respon- sive to folic acic} ant! Be when folic acid antagonists and a nonabsorbable sulfonamide were added to a base diet lacking folate and Be. Cartwright et al. reported in Petal! the striking changes involving blood, marrow, the central nervous system, and the liver that responder! fully anct specifically to the ad- dition of pyridoxine to a vitamin B6-deficient diet. Pigs also server! as subjects for important studies of iron, copper, ant! porphyrin metabolism studies later extended to man. Cartwright's investigations of hepatolenticular de- generation (Wilson's disease) ant! hereditary hemochroma- tosis were particularly noteworthy, while G. Richarc! Lee made important observations on the involvement of copper in iron metabolism, the role of the copper transport protein ceruloplasmin, and sicleroblastic anemia. The Utah group (particularly Jack Athens, G. E. Cartwright, A. M. Mauer, and Dane Boggs) also made highly significant investigations of leukocyte physiology and kinetics. Athens succeeded Cartwright as head of hematology in 1967. Boggs later transferred his studies of host defense mecha- nisms, leukocyte kinetics, and the hematopoietic stem cell to the University of Pittsburgh. There were many others in the Utah group students, residents, fellows, and faculty who

460 BIOGRAPHICAL MEMOIRS contributed to clinical and bench investigations of the leu- kemias, aplastic and sideroblastic anemias, the spleen, the hemogIobinopathies, coagulation disorders, and other as- pects of the spectrum of hematologic disease. At Utah, Jaeger ant! Wintrobe continued studies on chemical warfare agents they had begun in Baltimore during World War Il. The effects of nitrogen mustard on hemato- poiesis they observed lee! them to investigate its therapeutic usefulness in human neoplasia reported by Goodman et al. in 1946. Independently initiated therapeutic trials were re- porteci about the same time by Jacobsen et al. in Chicago. During the Utah years, the Wintrobes exploited Becky's talent as a hostess to initiate an annual garden party for new- comers, faculty, fellows, house staff, and town friends. The list of those attending this summer function eventually grew to more than 400 guests. They also enjoyed departmental picnics and bonfires at dusk in the canyons. Within an hour's cirive lay the beautiful Wasatch Mountains, the snows of Alta, and some of the worIct's finest skiing. It became a tradition that, on Wecines- day afternoons, the Department of Medicine at Utah was to be found skiing in the mountains. Max, along with George Cartwright, grew to love this recreation, and Cecil Watson described the Wednesciay afternoon jaunts as his "Maxiavel- lian" plan to promote morale and friendship within the De- partment and among the disciplines. Watson speculated that Max and George's love for, ant} skill at, skiing were aided by their physical constitutions and centers of gravity. Max had studied the violin in high school and carried over a love for chamber music. Though absorption in his profes- sion caused him to abandon music for many years, at Utah he again took up his violin, studying with the concertmaster of the Utah Symphony. He enjoyed playing chamber music with friends. On receiving the prestigious Ferrata Prize in

MAXWELL MYER WINTROBE 46 Rome, he used some of the associated monies to purchase an Enrico Politi violin. From 1963 to 1965 he served as a mem- ber of the Utah Symphony Board, becoming a member of its National Advisory Board after 1976. But there was also tragedy and adversity in Utah. In 1952, while in a car driven by friends, a collision on a slippery roar! resulted in the cleaths of the Wintrobe's son Paul, born in 1944, and of their friends' child. Max, Becky, and their claughter were also injured in the accident. CLINICAL HEMATOLOGY; PRINCIPLES OF INTERNAL MEDICINE; BLOOD, PURE AND ELOQUENT It would be difficult to overestimate the impact of Clinical Hematology on students, house officers, and hematologists since its initial publication in 1942. Authoritatively written, compendious, heavily and meticulously referenced and in- dexecI, there is no doubt that it was the premier textbook in hematology of its time. Nor can we appreciate how narrow was the scope and restricted the outlook of the field even as recently as the 1920s. The tenth edition of Osler's Principles and Practice of Medicine, published about the middle of that decade, devotes appreciably less space (thirty pages) to all the clisorders of blood combined than to the discussion of ty- phoid fever (forty-two pages). The eighth and most recent edition of Clinical Hematology (1981) ran to more than 2,000 pages. Max had written and edited the first six editions by himself, though always de- pencting on the unreserved, critical peer review and proof- reading of his talented colleagues at Utah, with Becky, as he saint, his severest ant] most helpful critic. The seventh and eighth editions were coauthored with several former fellows and associates. The eighth edition appeared in 1981, and Max was at work on the ninth at the time of his death in 1986. While recent years have seen other equally authorita-

462 BIOGRAPHICAL MEMOIRS tive and compendious hematology texts, Clinical Hematology was the prototype and remains a mode] of excellence in the fielcI. A second publishing endeavor highly valued by Max was the Principles of Internal Medicine (1950,1; 1954,3; 1974,1), with TinsIey R. Harrison as editor-in-chief. In 1950 when Principles was first published, Cecil and Loeb's excellent text enjoyed a near monopoly in its field. Harrison's Principles, with its emphasis on the pathophysiology and biochemistry of disease, opened the way for a new approach. Principles recommended diagnosis and treatment based not only on the signs and symptoms that brought the patient to the physician, but also on this pathophysiology. The original authors included Harrison, Resnick, Dock, Keefer, and Wintrobe, who were later joined by Paul Beeson, George Thorn, and others. Max was coeditor of this highly successful text through five editions, and the book was trans- lated into Portuguese, Italian, Polish, and Greek. For the sixth and seventh editions, he served as eclitor-in-chief. Max's final literary efforts sprang from a long-standing interest in medical history. Bloodt, Pure and Eloquent (1980,I), edited and partly authored by Max, was (like Clinical Hema- tology) dedicated "To Becky." It includes his own chapters on classic early discoveries in hematology, followed by chapters written by contemporary hematologists who themselves had made significant contributions to the subject areas of which they wrote. Most recently, his Hematology, the Blossoming of a Science: A Story of Inspiration and Effort ~~ 985,~ tells the human history of many contributors to the field through more than 500 biographical sketches. Writing this book as part memoir, part history, Wintrobe yet realizer! that he could never cover the lives of all who hacl contributed to "the Golden Age of hema- tology."

MAXWELL MYER WINTROBE RETIREMENT FROM THE CHAIR OF MEDICINE 463 In 1967 Max was succeeded at Utah as head of the De- partment of Medicine and physician-in-chief at the Univer- sity Hospital by George Cartwright; it can hardly be saic! he retired. As Distinguished Professor of Internal Medicine he continues} to see patients and, of course, write. He continued oIc! activities, initiated new ones, and receiver! a cascade of honors and awards after becoming emeritus. His curriculum vitae shows more than twenty visiting professorships at major universities in the United States and abroad after 1967. In 1977 the Wintrobes purchased a condominium in Palm Desert ant! thereafter spent the winter months in the more gentle climate of southern California. This meant an ens! to skiing but the opportunity to golf, write, edit, ant! relax. Many agencies private and governmental continued their clemanc] for Max's participation. As a senior statesman and ambassador his style underwent little change. He spoke in deep, carefully measured tones, ant! when he was in charge, he ran a tight ship. He never dispensed the fruits of experience ant! wisdom with the benignity of a Bernard Bar- uch, from a park bench. Fair and decisive, he hell! strong opinions, and he clic! not hesitate to express them and would scrap for a cause he believed in. Reminiscing in 1984, he stated that he was unequivocally happy to have accepted the challenge and come to Utah in 1943. As he looked back over the forty years since leaving Hopkins, a time that had been full of opportunities and crownec! with achievement, he and Becky couIct only con- clu(le they were glad they had ventured. When Max received his M.D. in 1926, the death sentence of a diagnosis of pernicious anemia hac! just been commuted ant! the discipline of hematology (essentially based on mor- phology) wouIcl never be the same. That same year Cooley

464 BIOGRAPHICAL MEMOIRS was to identify the anemia that bears his name, but the tha- lassemia syndromes their genetics, expression in heterozy- gotes, and molecular basis remained unknown. The first hospital-operated blooc! bank would not appear for more than another decade. The Rh-antigen system was undiscoverecI. The Coombs' test and autoimmune disease were unknown and the erythroenzymopathies unsuspected. The genetic code, the hemogIobinopathies and their molec- ular basis were not the subject of any text. Nobody knew of erythropoietin or discussed "B" and "T" lymphocytes, "col- ony stimulating factor," lymphokines, or granulocyte metab- olism and kinetics. There were no chemotherapeutic agents for malignant blooc! dyscrasias except the arsenical Fowler's solution employee! in treating chronic granulocytic leukemia. No one had thought of marrow transplants, genetic engi- neering, or the role of oncogenes. These fragments of the explosion of information uncov- ered between 1926 and Max's death in 1986 give some small idea of what he liked to call the Golden Age of Hematology. It was indeed a golden era and Max Wintrobe was one of its chief architects and ambassadors to the world. Max is survived by his wife, Becky; his (laughter, Susan; and his four grandsons, Andrew, Stephen, Timothy, and Davis! Brown.

MAXWELL MYER WINTROBE SELECTED BIBLIOGRAPHY 1929 465 With M. W. Miller. Normal blood determinations in the South. Arch. Intern. Med., 43:96. Hemoglobin standards in normal men. Proc. Soc. Exp. Biol. Med., 26:868. The volume and hemoglobin content of the red blood corpuscles. Am. I. Med. Sci., 177:513. A simple and accurate hematocrit. }. Lab. Clin. Med., 15:287. 1930 Blood of normal young women residing in a subtropical climate. Arch. Intern. Med., 45:287. Classification of the anemias on the basis of differences in the size and hemoglobin content of the red corpuscles. Proc. Soc. Exp. Biol. Med., 27:1071. The erythrocyte in man. Medicine, 9: 195. 1931 Hemoglobin content, volume and thickness of the red blood cor- puscle in pernicious anemia and sprue and the changes asso- ciated with liver therapy. Am. J. Med. Sci., 181:217. The direct calculation of the volume and hemoglobin content of the erythrocyte. Am. J. Clin. Path., 1:147. With I. H. Musser. Diseases of the blood. In: Tice Practice of Medi- cine. Hagerstown: W. F. Prior. Vol. 6, p. 739. 1932 The size and hemoglobin content of the erythrocyte. I. Lab. Clin. Med., 17:899. With L. I. Soffer. The metabolism of leukocytes from normal and leukemic blood. I. Clin. Invest., 11:661. 1933 Macroscopic examination of the blood. Am. }. Med. Sci., 185:58. With M. V. Buell. Hyperproteinemia associated with multiple mye- loma. Bull. Johns Hopkins Hosp., 52:156. With R. T. Beebe. Idiopathic hypochromic anemia. Medicine, 12:187.

466 BIOGRAPHICAL MEMOIRS With H. S. Shumacker, Jr. The occurrence of macrocytic anemia in association with disorder of the liver. Bull. Johns Hopkins Hosp. 52:387. Variations in the size and hemoglobin content of erythrocytes in the blood of various vertebrates. Fol. Haematol., 51:32. With I. W. Landsberg. Blood of normal men and women. Bull. Johns Hopkins Hosp., 53:118. 1935 With l. W. Landsberg. A standardized technique for the blood se- dimentation test. Am. I. Med. Sci., 189:102. With H. B. Shumacker, fir. Comparison of hematopoiesis in the fetus and during recovery from pernicious anemia. I. Clin. In- vest., 14:837. 1936 With H. B. Shumacker, [r. Erythrocyte studies in the mammalian fetus and newborn. Am. I. Anat., 58:313. 1937 The application and interpretation of the blood sedimentation test in clinical medicine. Med. Clin. North Am., 21:1537. 1939 The antianemic effect of yeast in pernicious anemia. Am.~. Med. Sci., 197:286. Diagnostic significance of changes in leukocytes. Bull. N.Y. Acad. Med., 15:223. With M. Samter and H. Lisco. Morphologic changes in the blood of pigs associated with deficiency of water-soluble vitamins and other substances contained in yeast. Bull. Johns Hopkins, 64:399. Nutritive requirements of young pigs. Am. J. Physiol., 126:375. 1940 With E. Matthews, R. Pollack, and B. M. Dobyns. A familial hem- opoietic disorder in Italian adolescents and adults. l. Am. Med. Assoc., 114: 1530. With I. L. Miller and H. Lisco. The relation of diet to the occur-

MAXWELL MYER WINTROBE 467 rence of ataxia and degeneration in the nervous system of pigs. Bull. Johns Hopkins Hosp., 67:377. 1941 Attempts to produce pernicious anemia experimentally. Bull. N. Engl. Med. Cent., 3:13. 1942 With C. Mushatt, I. L. Miller, fir., L. C. Kolb, H. l. Stein, and H. Lisco. The prevention of sensory neuron degeneration in the pig with special reference to the role of various liver fractions. I. Clin. Invest., 21:71. With H. J. Stein, M. H. Miller, R. H. Follis, Jr., V. Naiiar, and S. Humphreys. A study of thiamine deficiency in swine. Bull. Johns Hopkins Hosp., 71:141. With M. H. Miller, R. H. Follis, fir., H. J. Stein, C. Mushatt, and S. R. Humphreys. Sensory neuron degeneration in pigs. IV. Pro- tection afforded by calcium pantothenate and pyridoxine. I. Nutr., 24:345. With M. H. Miller, R. H. Follis, Jr., and H. I. Stein. What is the antineuritic vitamin? Trans. Assoc. Am. Physicians, 57:55. Clinical Hematology. Philadelphia: Lea & Febiger. 1943 With R. H. Follis, Jr., M. H. Miller, H. J. Stein, R. Alcayaga, S. Humphreys, A. Suksta, and G. E. Cartwright. Pyridoxine defi- ciency in swine, with particular reference to anemia, epilepti- form convulsions and fatty liver. Bull. Johns Hopkins Hosp., 72:1. 1944 With G. E. Cartwright and S. Humphreys. Studies on anemia in swine due to pyridoxine deficiency, together with data on phen- ylhydrazine anemia. J. Biol. Chem., 153: 171. With G. E. Cartwright, P. ~ones, M. Lauritsen, and S. Humphreys. Tryptophane derivatives in the urine of pyridoxine-deficient swine. Bull. Johns Hopkins Hosp., 75:35. With W. Buschke, R. H. Follis, Jr., and S. Humphreys. Riboflavin deficiency in swine, with special reference to the occurrence of cataracts. Bull. Johns Hopkins Hosp., 75:102.

468 BIOGRAPHICAL MEMOIRS With R. H. Follis, fir., S. Humphreys, H. Stein, and M. Lauritsen. Absence of nerve degeneration in chronic thiamine deficiency in pigs. l. Nutr., 28:283. 1945 Relation of nutritional deficiency to cardiac dysfunction. Arch. In- tern. Med., 76:341. With H. J. Stein, R. H. Follis, Jr., and S. Humphreys. Nicotinic acid and the level of protein intake in the nutrition of the pig. J. Nutr., 30:395. 1946 With G. E. Cartwright, M. A. Lauritsen, S. Humphreys, P. J. Jones, and I. M. Merrill. The anemia associated with chronic infection. Science, 103:72. With G. E. Cartwright, M. A. Lauritsen, P. I. tones, and P. I. Merrill. The anemia of infection. I. Hypoferremia, hypercupremia, and the alterations in porphyrin metabolism in patients. J. Clin. In- vest., 25:65. With G. E. Cartwright, M. A. Lauritsen, S. Humphreys, P. J. Jones, and I. M. Merrill. The anemia of infection. II. The experimen- tal production of hypoferremia and anemia in dogs. I. Clin. Invest., 25:81. With L. S. Goodman, W. Dameshek, M. l. Goodman, A. Oilman, and M. T. McLennan. Nitrogen mustard therapy. Use of methyl-big (beta-chloroethyl) amine hydrochloride and tris (beta-chloroethyl) amine hydrochloride for Hodgkin's disease, lymphosarcoma, leukemia and certain allied and miscellaneous disorders. J. Am. Med. Assoc., 132: 126. With G. R. Greenberg and G. E. Cartwright. The pathogenesis of the anemia of infection. Trans. Assoc. Am. Physicians, 59:110. 1947 With G. R. Greenberg, S. R. Humphreys, H. Ashenbrucker, W. Worth, and R. Kramer. The anemia of infection. III. The uptake of radioactive iron in iron-deficient and in pyridoxine- deficient pigs before and after acute inflammation. I. Clin. In- vest., 26:103. The mammalian red corpuscle. Blood, 2:299. With M. Grinstein, }. I. Dubash, S. R. Humphreys, H. Ashen-

MAXWELL MYER WINTROBE 469 brucker, and W. Worth. The anemia of infection. VI. The influ- ence of cobalt on the anemia associated with inflammation. Blood, 2:323. With C. M. Huguley, Jr., M. T. McLennan, and L. P. C. Lima. Ni- trogen mustard as a therapeutic agent for Hodgkin's disease, lymphosarcoma and leukemia. Ann. Intern. Med., 27:529. With M. T. McLennan and C. M. Huguley, Tr. Clinical experiences with nitrogen mustard therapy. In: Approaches to Tumor Chemo- therapy, p. 347. 1948 With G. E. Cartwright. Studies on free erythrocyte protopor- phyrin, plasma copper, and plasma iron in normal and in pyr- idoxine-deficient swine. I. Biol. Chem., 172 :557. Nitrogen mustard therapy. Am. J. Med., 4:313. With M. Grinstein and J. A. Silva. The anemia of infection. VII. The significance of free erythrocyte protoporphyrin, together with some observations on the meaning of the "easily split-off" iron. }. Clin. Invest., 27:245. With G. E. Cartwright, J. Fay, and B. Tatting. Pteroylglutamic acid deficiency in swine: effects of treatment with pteroylglutamic acid, liver extract and protein. I. Lab. Clin. Med., 33:397. With C. M. Huguley, fir. Nitrogen-mustard therapy for Hodgkin's disease, lymphosarcoma, the leukemias, and other disorders. Cancer, 1:357. With G. E. Cartwright. Studies on free erythrocyte protopor- phyrin, plasma copper, and plasma iron in protein-deficient and iron-deficient swine. I. Biol. Chem., 176:571. 1949 With G. E. Cartwright, B. Tatting, and H. Ashenbrucker. Experi- mental production of a nutritional macrocytic anemia in swine. Blood,4:301. With G. E. Cartwright. Further studies on nutritional macrocytic anemia in swine. Trans. Assoc. Am. Physicians, 62:294. 1950 Eds., M. M. Wintrobe, T. R. Harrison, P. B. Beeson, W. H. Resnik, G. W. Thorn. Principles of Internal Medicine. Philadelphia: The Blakiston Company.

470 BIOGRAPHICAL MEMOIRS 1951 With G. E. Cartwright, M. E. Lahey, and C. J. Gubler. The role of copper in hemopoiesis. Trans. Assoc. Am. Physicians, 64:310. Clinical Hematology, ad ed. Philadelphia: Lea & Febiger. 1952 Factors and mechanisms in the production of red corpuscles. In: Harvey Lectures, 45. Springfield: C. C. Thomas. With R. K. Smiley and G. E. Cartwright. The anemia of infection. XVII. A review. Ad. Intern. Med., 5: 165. 1953 With G. E. Cartwright and C. I. Gubler. Studies on the function and metabolism of copper. J. Nutr., 50:395. Shotgun antianemic therapy. Am. I. Med., 15: 141. 1954 With G. E. Cartwright, P. Fessas, A. Haut, and S. J. Altman. Chemo- therapy of leukemia, Hodgkin's disease and related disorders. Ann. Intern. Med., 41:447. With G. E. Cartwright, R. E. Hodges, C. J. Gubler, J. P. Mahoney, K. Daum, and W. B. Bean. Studies on copper metabolism. XIII. Hepatolenticular degeneration. I Clin. Invest., 33: 1487. Eds. M. M. Wintrobe, T. R. Harrison, R. D. Adams, P. B. Beeson, W. H. Resnik, and G. W. Thorn. Principles of Internal Medicine. New York: McGraw-Hill. 1955 With P. Fessas and G. E. Cartwright. Angiokeratoma corporis dif- fusum universale (Fabry). Arch. Intern. Med., 68:42 and 95:469. 1956 Clinical Hematology. 4th ed. Philadelphia: Lea & Febiger. With G. E. Cartwright. Blood disorders caused by drug sensitivity. Arch. Intern. Med., 96:559.

MAXWELL MYER WINTROBE 1957 471 The search for an experimental counterpart of pernicious anemia (The George Minot Lecture). Arch. Intern. Med., 100:862. 1961 Clinical Hematology, 5th ed. Philadelphia: Lea & Febiger. 1964 The therapeutic millennium and its price. Adverse reactions to drugs. In: Drugs in Our Society. Baltimore: Johns Hopkins Press. With G. E. Cartwright. Copper metabolism in normal subjects. Am. J. Clin. Nutr., 14:224. With G. E. Cartwright and I. W. Athens. The kinetics of granulo- poiesis in normal man. Blood, 24:780. 1965 The problems of drug toxicity in man—a view from the hemato- poietic system. Ann. N.Y. Acad. Sci., 123:316. The virtue of doubt and the spirit of inquiry (Presidential Address, Assoc. Am. Phys., Atlantic City, May 1965~. Trans. Assoc. Am. Physicians, 78:1. 1966 The problem of adverse drug reactions. Am. Med. Assoc., 196:404. 1967 A hematological odyssey, 1926-66. Johns Hopkins Med. J., 120:287. 1969 The therapeutic millennium and its price: A view from the he- matopoietic system. J. R. Coll. Phys. (London), 3:99. Anemia, serendipity, and science. J. Am. Med. Assoc., 210:318. 1974 Ed. M. M. Wintrobe. Harrison's Principles of Internal Medicine, 7th ed. New York: McGraw-Hill. With others. Clinical Hematology, Philadelphia: Lea & Febiger, 7th ed.

472 BIOGRAPHICAL MEMOIRS 1980 With others. Blood, Pure and Eloquent. A Story of Discovery of People, and of Ideas. New York: McGraw-Hill. 1981 With others. Clinical Hematology. Philadelphia: Lea & Febiger, 8th ed. 1982 Medical education in Utah (Medical schools of the west). West. I. Med., 136:357. 1985 Hematology, the Blossoming of a Science: A Story of Inspiration and Effort. Philadelphia: Lea & Febiger.

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Biographic Memoirs Volume 59 contains short biographies of deceased members of the National Academy of Sciences.

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