Internal Medicine

Internal Medicine

Medical School

The University of Michigan: An Encyclopedic Survey Copyright © 2015 by the Regents of the University of Michigan

The University of Michigan: An Encyclopedic Survey was first published beginning in 1942. For its 2017 Bicentennial, the University undertook the most significant updating of the Encyclopedia since the original, focusing on academic units. Entries from all versions are compiled in the Bicentennial digital and print-on-demand edition. Contents

1. Internal Medicine (1942) 1 Cyrus C. Sturgis, Frank N. Wilson, and Arthur C. Curtis

2. Internal Medicine (1975) 22 Fred J. Hodges

3. Internal Medicine (2016) 24 Joel D. Howell

[1]

Internal Medicine (1942)

Cyrus C. Sturgis, Frank N. Wilson, and Arthur C. Curtis

The Period Ending in 1908

THE first step in organizing the Department of Medicine was the appointment in 1848 of Abram Sager (Rensselaer Polytechnic Institute ’31, M.D. Castleton Medical College [Vt.] ’35, A.M. hon. Michigan ’52) as Professor of the Theory and Practice of Medicine. He had been Professor of Botany and Zoology since 1842, but apparently never conducted classes in medicine, as in January, 1850, Samuel Denton (M.D. Castleton Medical College [Vt.] ’25) was appointed to the professorship in medicine as well as to that in pathology, and Sager was assigned to the professorship of obstetrics and diseases of women. In 1874 Sager was made Emeritus Professor, but he continued to act as Dean until June, 1875, when he resigned as a protest against the proposed establishment of a department of homeopathy in the Medical School. The first active head of the Department of Medicine was Samuel Denton, who had been appointed Professor of the 2 Internal Medicine

Theory and Practice of Medicine and Pathology in 1850. In 1837 he had been appointed one of the first Regents and he had served for three years; later, his interest in state politics led to service in the state Senate from 1845 to 1848. According to Dr. William Fleming Breakey, Denton was very dignified in manner and always wore a high hat. He had a large general practice and was much sought in consultation, for he had an excellent reputation for sound judgment and skill in diagnosis and treatment. A great advocate of the use of alcohol in many types of illness, he especially recommended it in “consumption” and in the later stages of protracted fevers. The discrepancy between his views and those of Dr. Alonzo B. Palmer, who bitterly opposed the use of alcohol in all forms, was quickly noticed by the students, who sometimes submitted written questions in class calling attention to the opposing opinions. According to Dr. Victor C. Vaughan, Denton “possibly had something to do with the inauguration of the Medical School, but so far as I can learn he contributed but little to its reputation” (Vaughan, A Doctor’s Memories, p. 195). He died in Ann Arbor, August 17, 1860. To succeed him Samuel Glasgow Armor (M.D. Missouri Medical College ’44, LL.D. Franklin ’72) was, in 1861, appointed Professor of the Principles of Medicine and Materia Medica, although the title was changed at once, by his request, to Professor of the Institutes of Medicine and Materia Medica. He had held teaching positions in several middle western medical colleges and was in private practice in Dayton, Ohio, when he accepted the appointment, which he retained until the close of the session of 1867-68. Dr. Armor, a man of great personal charm, was characterized as an able teacher and lecturer, although he will not be remembered as one who contributed importantly to the advancement of medicine. He made his home in Detroit and was in practice there, for a part of the time, in professional partnership with Dr. Moses Gunn, who was then Professor of Surgery in the University. Alonzo Benjamin Palmer (M.D. College of Physicians and Surgeons [West. Dist., N. Y.] ’39, LL.D. Michigan ’81) became associated with the University in 1854, when he was appointed Professor of Materia Medica, Therapeutics, and Diseases of Internal Medicine (1942) 3

Women and Children. Appointed Professor of Anatomy two years before, he was listed as “not on duty,” presumably because of his desire to accumulate more funds before beginning an academic life. For a time Palmer attempted to maintain a residence in Chicago, but soon gave this up and came to Ann Arbor to live. On the death of Denton in 1860 he assumed the professorship of the theory and practice of medicine and of pathology and materia medica, becoming, a year later, Professor of the Theory and Practice of Medicine and of Pathology, in 1864 Professor of Pathology, the Practice of Medicine, and Hygiene, and in 1869 Professor of Pathology and the Practice of Medicine. His title from 1880 until his death was Professor of Pathology and of the Practice of Medicine and Clinical Medicine. Thirty-three years of his life were devoted to teaching medicine in the University; the last twelve of these he served as Dean. During the years of his residence in Ann Arbor Dr. Palmer was an active member and vestryman of Saint Andrew’s Church, where as a lay reader he often conducted services and taught a students’ Bible class. With Mrs. Palmer he gave a substantial sum toward the erection of the church tower. After his return from Europe in 1879 he became a warm friend of Bishop Harris of the Detroit diocese and took the deepest interest in the founding of the Hobart Guild. In 1859, when he was forty-four, he made his first European trip. His diary shows that in London he attended clinics and lectures at Guy’s Hospital, Saint Bartholomew’s Hospital, the London Fever Hospital, King’s College Hospital, Saint Thomas Hospital, Middlesex Hospital, and the Children’s Hospital. He met many prominent medical men, among them Charles Murchinson, famed for his studies on fevers and for emphasizing the importance of milk in the spread of typhoid fever. He spoke of having met Sir Benjamin C. Brodie, then seventy-six years of age, the president of the Royal College of Surgeons, and Sir Alfred B. Garrod, well known for his studies on gout. After three months in London he spent five weeks in Paris. There he visited Charles Eduard Brown-Séquard, who succeeded Claude Bernard as the professor of experimental medicine in the Collège de France in 1878 and who is chiefly 4 Internal Medicine

remembered for his experimental investigations of the nervous system. He also saw Auguste Nelaton, one of the surgeons to Napoleon III, and Alfred Armand Louis Marie Velpeau, surgeon at the Charité, well known for his work on surgical anatomy and his New Elements of Operative Surgery. Palmer was especially interested in the clinic of Pierre-Adolph Piorry, inventor of the pleximeter and a pioneer in mediate percussion. In his diary he recorded: “Piorry [is] famous for his percussion; pretends to tell more by percussion than anyone else, and probably can do it.” This is of interest because Palmer was a master of physical diagnosis himself and drilled his students thoroughly in its methods. He also visited the clinic of Armand Trousseau, one of the leading clinicians and medical teachers of France. In Dublin he spent a morning with William Stokes, regius professor of medicine, who, as early as 1825, had published an Introduction to the Use of the Stethoscope. He had also written on cholera, having observed the Dublin epidemic of 1832, and was well known for his description of the Stokes-Adams syndrome and for his contributions to the literature dealing with diseases of the chest, heart, and aorta. As a delegate of the American Medical Association, Palmer attended the meeting of the British Association for the Advancement of Science at Aberdeen, where he met and heard the most illustrious scientific men of Great Britain. Later, at Edinburgh, he called upon Sir James Young Simpson, one of the most remarkable personalities of his time, who was the first to employ chloroform as an anesthetic. He also made many contributions to obstetrics and gynecology and was greatly interested in improving the status of hospitals. The European trip was doubtless a great inspiration to Palmer, for he came in contact with the finest type of physicians and medical teachers of Great Britain and France and visited most of the important hospitals and medical schools. Why he did not visit Germany is not known. The French, however, had contributed most of the advancements in medicine until about 1850. On his return Palmer entered into his work with enthusiasm. Apparently he was an inspiring teacher; he sincerely enjoyed lecturing and was always ready to substitute for other lecturers Internal Medicine (1942) 5 in emergencies, or to add new lectures of his own if he thought there was a need for them. The memorial to him stated:

His lectures were at first fully written out but latterly he took briefer notes into the lecture room, carefully and systematically arranged. He never appeared before his class without looking over his notes and getting his subject well in hand; he was constantly rewriting and rearranging his lectures, to keep them abreast of scientific advancement. (Memorial of … Palmer, p. 167.)

That he was thorough and meticulous in the examination of patients may be surmised by his comments on Dr. Walshe, whose clinic he visited in London:

I have been particularly interested in Dr. Walshe’s clinical exercises in the hospital. I have never witnessed more searching, exact, and intelligent examination of patients, particularly in all cases of diseases of the chest. Nothing could exceed the minute care exercised in physical explorations, and, so far as I could judge from witnessing his procedures, and hearing his remarks, with occasional examinations of particular sounds, he is unusually discriminative and precise in his observations, and very just in his conclusions. (Memorial of … Palmer, p. 27.)

Breakey says that Palmer was “energetic, ambitious, industrious, and loved teaching.” To the alumni attending the Commencement of 1888, the year following Palmer’s death, Dr. Elijah H. Pilcher characterized him as follows:

[He was] earnest and methodical, learned and painstaking, pure and stainless in his life, kindly and benevolent, tenacious of what he thought to be right, devoted to the interests of the University; for more than a generation of years he was one of the most conspicuous figures of the medical faculty. (Memorial of … Palmer, p. 170.)

Vaughan commented, in A Doctor’s Memories (p. 199):

He drilled his students ad nauseam in the employment of instruments of precision; auscultation and percussion were not only his favorite hobbies, but in their use he showed great skill. I remember how proudly he exhibited to me the first laryngoscope I ever saw. 6 Internal Medicine

Although he was an ardent Whig and abolitionist, his Civil War service was relatively brief. He resigned a commission as surgeon of the 2d Regiment of Michigan Volunteers on September 23, 1861, after a service of five months, to resume his University teaching. In 1863 he accepted the chair of the theory and practice of medicine at the Berkshire Medical College in Pittsfield, Massachusetts, and during his first summer of service there also gave the lectures on materia medica. The plan of holding two professorships simultaneously at different medical institutions was not unusual and apparently was sanctioned by the University. At least two other medical teachers of the University had a similar arrangement: Corydon L. Ford, Professor of Anatomy, lectured in his subject at the same institution, and Armor, Professor of the Institutes of Medicine and Materia Medica, lectured at the Long Island Hospital Medical College. This arrangement was possible because the University’s term of medical instruction lasted only six months. In 1877 the annual term of the Medical Department at Ann Arbor was extended to nine months, causing a conflict with Palmer’s chair of the practice of medicine in the Medical School of Maine, which he had held since 1869. During the school year 1877-78, by lecturing twice daily, he managed to give the full number of lectures at both places. At the suggestion of many of his former pupils Palmer wrote a textbook, A Treatise on the Science and Practice of Medicine, which appeared in 1883 in two volumes of about nine hundred pages each. Although its immediate reception was flattering this work could not be regarded as a great success. According to Vaughan, “Had it been presented fifteen years earlier it would have had a wide circulation, but it came just when the new medicine was supplanting the old and is now unknown and unused” (A Doctor’s Memories, p. 199). Dr. Palmer was not a prolific writer, as there are only twelve publications recorded in his memorial book. They deal with homeopathy, the effects of alcohol and temperance teachings, the cause of typhoid fever, sulphate of quinine, epidemic cholera, the treatment of inflammation of internal organs, and medical teaching. His president’s address before the Michigan Internal Medicine (1942) 7

State Medical Society in 1873 had the title, “Law and Intelligence in Nature, and the Improvement of the Race in Accordance with Law.” During the last decade of Palmer’s life many changes occurred in the Medical School which had his support and the benefit of his influence. Two pavilions were added in 1876 to the residence which served as a hospital on the north side of the campus, and this greatly increased the bed capacity; in 1877 the sessions were extended from six to nine months; in 1880 attendance for three years was required for graduation; a more extended course in physiological chemistry was begun in 1878; and in 1879 practical work in physiology was instituted (the course in physiological chemistry had previously been limited to urinalysis). The following items from the Calendar of 1884-85 illustrate the subjects considered as belonging to the department and the time devoted to them: Urinalysis, twelve weeks of afternoon work; Physical Diagnosis, thirty-two hours in lecture room and hospital; the Practice of Medicine, 180 hours in the general lecture room; and Clinical Medicine, 148 hours in the Hospital amphitheater. After the death of Dr. Palmer in 1887, Dr. Henry Francis LeHunte Lyster (’58, ’60m, A.M. ’61) was made Professor of the Theory and Practice of Medicine and Clinical Medicine, and he served in this capacity in 1888-89 and in 1889-90. Apparently he continued his practice in Detroit while he was head of the Department of Medicine in the University. It was during Dr. Lyster’s regime that the separate Department of Pathology was created. No professor of internal medicine was appointed for the year 1890-91, but the acting head was Dr. Walter Shield Christopher (M.D. Medical College of Ohio [Cinn.] ’83), who was listed as Lecturer on the Theory and Practice of Medicine and Clinical Medicine. Dr. George Dock’s explanation was as follows:

All professors were elected as lecturers and only given the title of Professor if, toward the end of the year, they were recommended for full title with indefinite tenure. Christopher was a very bright fellow but more interested in pediatrics. He went to Chicago in 1891 and became a very popular consultant, but died young. 8 Internal Medicine

George Dock (M.D. Pennsylvania ’84, A.M. hon. Harvard ’95, Sc.D. hon. Pennsylvania ’04) was the next appointee to the chair of the theory and practice of medicine and clinical medicine. This was an important appointment, as he probably contributed more to the development of the department than any other professor before or since. In addition to his remarkable natural ability as a physician, teacher, and investigator, he had received the advantages of the best medical education obtainable at that time. After his graduation from Pennsylvania, he served as an intern at Saint Mary’s Hospital in Philadelphia and then spent two years in study at Berlin, Leipzig, Frankfort, and Vienna. Medicine at this time was developing at a rapid rate, and German medicine was conceded to be the most progressive in the world. Dock returned to Philadelphia in 1887 as an assistant in clinical pathology, under the influence of William Osler and John M. Musser, two of the most inspiring medical teachers of all time. These experiences must have had a large share in developing his scientific knowledge and his teaching ability, which endeared him to many classes of students at the University. The status of the Department of Medicine apparently was none too satisfactory in the few years prior to Dock’s arrival. At the time of his appointment, the Michigan Daily reported that the chair of the theory and practice of medicine had had a “checkered career, as more than the ordinary changes [had] caused a feeling of uncertainty in the minds of the medical students. This feeling [had] been dissipated by the appointment of Dr. Dock.” He took up his work in September, 1891. In the following year Aldred Scott Warthin (Indiana ’88, Michigan ’91m, Ph.D. ibid. ’93, LL.D. Indiana ’28) was appointed Demonstrator of Clinical Medicine. According to Dock:

There were no available doctors in the city to act as volunteers and on account of my late appointment there were no senior men available to assist with the teaching. Warthin and I were literally on full time, working in the hospital or on outpatients from eight to six, and often seeing patients at night.

The condition of affairs on his arrival may be summarized by his own words: Internal Medicine (1942) 9

Before my time medical patients were rarely admitted to the hospital. The space was filled with operative cases. When I arrived on the ground there were no medical patients in sight, and I gave my first clinic on a private patient of Dr. Breakey who had pleurisy with effusion. Very soon we sent out, with the consent of the faculty, letters to physicians and preachers saying that there was an outpatient service in the hospital for medical cases and that the attendants (Warthin and I) would see indigent patients or any referred by physicians at their homes. We quickly gathered up a lot of good stuff. (From a letter written on March 1, 1937, to Richard C. Boelkins, a fourth-year medical student at the University.)

During Dock’s early days at the Hospital the clinical facilities of the Medical School were greatly improved by the completion of the Catherine Street Hospital in December, 1891, providing at first sixty-four beds. This was later known as the West Hospital. Dr. Dock will be remembered for his many fine qualities and for the important innovations he introduced into medical teaching at the University. He was chiefly instrumental in organizing laboratory methods of teaching and in reorganizing the course in auscultation and percussion. He likewise insisted that the work in medicine should not consist of the repetition of lectures in two successive years, as had previously been the custom. His bibliography for the eighteen years he was on the staff of the Medical School contains eighty-three medical articles. They deal with many different topics and indicate his thorough knowledge and broad interest in clinical medicine. Among the subjects to which he made original contributions were chloroma, leukemia, Banti’s disease, Hodgkin’s disease, malaria, amoebic dysentery, osteomalacia, endocarditis, coronary thrombosis, tuberculosis, diabetes, and lobar pneumonia. In addition, he wrote the section dealing with endocrinology in Osler’s Modern Medicine, published in 1909 and recognized as the leading system of medicine in the English language at that time. Dock edited and contributed additions to the volume Diseases of the Heart (1908), in Nothnagel’s Encyclopedia of Practical Medicine, which was the translation of one of the outstanding systems of medicine published in Germany. Dr. Dock’s interest in tuberculosis is shown by his publications on this subject, including one in 1902 on “Some Reasons Why There Should Be 10 Internal Medicine

a Hospital for Consumptives in Connection with the University Hospital.” His wide interest in the constant advances of medicine led him, in association with Vaughan and Warthin, to devote much time and thought to the development of the Medical Library. As a result, early in the history of the Medical School a remarkably complete library was organized. His interest in this work led in 1907 to an article on “The Medical Library of the University of Michigan.” Many young medical students, stimulated by Dock’s teaching, later came to occupy positions of prominence in this country. Dr. Aldred Scott Warthin, one of his first associates, became Professsor of Pathology in the University. Dr. David Murray Cowie became Instructor in Pediatrics in 1905, and in later years served as Professor of Pediatrics and Infectious Diseases and head of that department. Dr. James Rae Arneill (Lawrence ’90, Michigan ’94m, LL.D. Lawrence ’23), of Denver, Colorado, was Instructor in Internal Medicine from 1898 to 1903, and later became professor of medicine at the University of Colorado. Dr. Roger Sylvester Morris (’00, ’02m) was later associated with the Medical Department of Johns Hopkins University and finally became professor of medicine at the University of Cincinnati. Dr. James Gerrit Van Zwaluwenburg (’98, ’08m) became Professor of Roentgenology in the University. In addition to the group named, many others who were his students and who in some instances were associated with him on the staff of the Department of the Theory and Practice of Medicine went to different parts of the country and became the leading consultants and practitioners in their communities. In 1896 Dr. Dock was offered a position as professor of medicine at Jefferson Medical College in Philadelphia, but he declined it. He left in 1908 to become professor of medicine at Tulane University, and later accepted a chair in Washington University, St. Louis, which he resigned in 1922 to take up private practice in Pasadena. Cyrus C. Sturgis Internal Medicine (1942) 11

The Years 1908-27

After the resignation of Dr. Dock, the dean and faculty of the Medical School (then called the Department of Medicine and Surgery) attempted at first to obtain Dr. Rufus Cole of Johns Hopkins University as his successor. In declining their offer Cole mentioned Albion Walter Hewlett (California ’95, M.D. Johns Hopkins ’00) as a possibility and recommended him in the highest terms to the Regents, who in 1908 appointed him Professor of Internal Medicine and Director of the Clinical Laboratory. This position he held until 1916, when he resigned to become professor of medicine at Leland Stanford Junior University. While at Ann Arbor Hewlett made a rather extensive study of the blood flow in the arm in various clinical conditions and wrote a book on the Functional Pathology of Internal Diseases, accepted as an authoritative work on this subject. Hewlett was one of the first men appointed to the chair of medicine in an important medical school whose chief interest lay in the functional rather than in the structural aspects of disease — in pathologic physiology rather than in pathologic anatomy. He had a strong instinct for research, and his reputation rested more upon his attainments in the field of productive scholarship than upon his renown as a clinician. During his stay at Ann Arbor he was continuously engaged in research himself and did his utmost to stimulate his assistants to do likewise. Although the salary he received from the University was small, judged by present standards, he refused to open an office for the practice of medicine and would not grant this privilege to his assistants. Dr. Hewlett was not a spectacular teacher or clinician, unlike Dr. Dock, whose striking personality immediately made a strong and lasting impression upon those who came in contact with him. One of Hewlett’s most striking traits was his intellectual honesty. When he made a mistake in diagnosis he acknowledged it freely and without embarrassment and never offered an excuse. His mind was of the very first caliber, but he never paraded his knowledge or sought to dramatize his lectures and clinics. In his character there was no taint of selfishness. He took pride in the accomplishments of his 12 Internal Medicine

assistants, and when he worked with them on a problem or directed their research he saw to it that they received more than their full share of credit for the work done. When the time came for them to leave the department he did all in his power to help them pursue their chosen careers and followed their progress with great personal interest. Of the men who were associated with Dr. Hewlett, Dr. James Howard Agnew (’07, A.M. ’08, ’10m) became, for a time, professor of medicine at the University of Alabama; Dr. Luther Fiske Warren (’07, ’09m), professor of medicine at Long Island Medical College; and Dr. Van Zwaluwenburg, Professor of Roentgenology in the University. Soon after his arrival at the University Hewlett called attention to a recent epidemic of scarlet fever in the medical wards and pointed out the great need for a contagious hospital. It is not surprising, in view of what has been said of his chief interests, that in a discussion as to whether the primary function of the University Hospital was to supply the Medical School with the clinical material necessary for the instruction of its students and for the investigation of disease, or whether one of its major functions was to furnish medical service to the citizens of the state of Michigan, he championed the former view. When he first came to Michigan the instruction in the Department of Medicine was confined to the junior and senior years. A junior course in clinical microscopy, given four times a year and once during the summer session, had as its purpose instruction in the technique employed in the examination of the blood, sputum, stomach contents, and excreta, and dealt also with the diagnostic significance of the data furnished by these methods. It was under the charge of the junior instructor in the department and was given in turn by Dr. Warren, Dr. Harry Burke Schmidt (’11m), Dr. Frank N. Wilson (’11, ’13m), and Dr. Quinter Olen Gilbert (’09, A.M. ’10, ’14m). In a second junior course, at first called Auscultation and Percussion and later Physical Diagnosis, instruction was given in the technique of the physical examination of the patient and in the interpretation of the data obtained. This course was conducted at first by Van Zwaluwenburg and later by the senior instructor in the department. Internal Medicine (1942) 13

A third course consisted in the presentation of typical cases illustrating the more common internal diseases occurring in the Hospital. At each meeting the class was quizzed on the subject presented at the preceding meeting. These clinics, given by Dr. Hewlett, covered etiology, symptomatology, and physical signs. Differential diagnosis and treatment were left for consideration in the senior year. A second part in this course, given by an assistant, consisted in assigned reading, quizzes, and frequent written tests, and dealt with diseases less common and not ordinarily encountered in the Hospital. This didactic work was later given up in favor of additional clinics. In the senior year Dr. Hewlett gave two clinics weekly, at which cases were presented and the diagnosis, differential diagnosis, and appropriate treatment were fully discussed. On each clinic day he selected the cases and spent some time in preparing his material. The major course of the senior year was “case taking,” in which the students, by sections, were assigned the patients admitted to the medical wards. Ordinarily the students worked in pairs, were responsible for the history and routine laboratory tests, and were expected to complete these with as great dispatch as possible. The data collected by them were incorporated in the Hospital records, and their work was supervised but was not repeated by the house officer in charge of the ward. The students were also expected to make a complete physical examination and to keep progress notes, but this material was collected solely for their own use and did not become a part of the permanent record. During daily ward rounds by Hewlett or the senior instructor the students presented their cases for discussion. For a number of years a “medical staff” was appointed, consisting of a small group of students, selected because of their scholastic standing or interest in internal medicine. These students were assigned medical cases throughout the year instead of merely during the period when the section to which they belonged was on the medical wards. Hewlett made special rounds each Sunday morning for their benefit, and the cases assigned to them were then presented. In 1911 an introductory course in physical diagnosis for sophomore students was given for the first time by Dr. Warren. 14 Internal Medicine

It was continued by the junior instructors who followed him. In 1915 Hewlett offered a one-hour course in pathologic physiology. Up to this time very little provision for the care of outpatients had been made in the Department of Medicine. In a small room adjoining the office of the Department of Neurology an occasional outpatient was seen by the assistant in medicine, but the number of outpatients gradually increased, and it became necessary to make some provision for them. After declining an offer from the University of Minnesota in 1915-16 Dr. Hewlett requested and received a special appropriation for the construction of an outpatient service in the basement of the medical wing of the old University Hospital. Shortly after this he accepted the chair of medicine at Leland Stanford. Dr. Hewlett was succeeded by Nellis Barnes Foster (Amherst ’98, M.D. Johns Hopkins ’02), who had pursued postgraduate studies in various European institutions before becoming associated with Cornell Medical College in New York City. Foster arrived in Ann Arbor in the fall of 1916 and found the department established in the old Medical Ward, which burned in 1927. This building had twenty-three beds, and there was no formal outpatient service. A small room, measuring about five by ten feet, provided the only available space for experimental work. From this the work in experimental medicine developed. In order that the department could have more space Vaughan permitted Dr. Louis Harry Newburgh (Harvard ’05, M.D. ibid. ’08) to work in the Hygienic Laboratory in the basement of the West Medical Building. Shortly after Dr. Foster arrived he was assigned space in an old building which had formerly housed the Hospital laundry, and the Regents appropriated about $2,000 for the purchase of laboratory equipment for it. The one large room of this building was over the Hospital furnace and was very hot in summer, especially as the structure also had a sheetiron roof. The room was so dark that it was necessary to have the electric lights turned on in the middle of the day. An L-shaped room was partitioned off, and arrangements were made to divide it into four small laboratories. Small experimental animals, such Internal Medicine (1942) 15 as guinea pigs and rabbits, were kept at one end. The remainder of the room was used for teaching purposes. Dr. Foster had a very high regard for Vaughan, Novy, Warthin, Huber, and others of the faculty, and it was, perhaps, on account of their reputations that he was attracted to Ann Arbor. He was full of enthusiasm and did much teaching. He acted in consultation with Dr. Newburgh and Dr. Mark Marshall (Earlham ’02, Michigan ’05, ’08m), each of whom had charge of a ward. Dr. Foster had served in his position for only five or six months when the United States entered World War I. Shortly afterward he suddenly left the University, as a result of a misunderstanding with Dr. Vaughan, who was then Dean, and joined the Medical Corps of the United States Army. The differences with Dr. Vaughan probably were not initiated by Dr. Foster, and apologies were offered to him later. He was a most pleasing type of physician, exceedingly well grounded in clinical medicine, and beloved by all members of the department. When Dr. Foster left Ann Arbor, Newburgh was advised by Vaughan that he was to be the acting head of the department, but was cautioned that he could not have a free hand in conducting the department, as he could not have control of its budget, and that he would not have the privilege of recommending new appointments. Newburgh was then made chairman of a committee to select a successor, but after considering several physicians of prominence in the Middle West and East, the committee was discharged, as it could not obtain a suitable man for the position. Newburgh had come to the University of Michigan in 1916 as Assistant Professor of Medicine, upon the recommendation of Foster. He had served for four years as alumni assistant at the Harvard Medical School, working with Dr. James Howard Means, later professor of medicine at that institution, and Dr. William Townsend Porter, then professor of physiology. His investigations during this interval were concerned chiefly with studies on the respiration, the circulatory rate, and the effect of strychnine on the blood pressure in patients with pneumonia. Upon arrival in Ann Arbor he immediately began to develop an experimental laboratory which, as a result of his efforts, has now 16 Internal Medicine

grown into the splendidly equipped nutrition laboratory that functions as a unit of the Department of Internal Medicine. Dr. Newburgh served as active head of the department in 1917-18, and was appointed Professor of Clinical Investigation in Internal Medicine in 1922. Hugh Cabot (Harvard ’94, M.D. ibid. ’98), then Dean of the School, in his report to the President for 1921-22 stated: “It is believed to be essential for the satisfactory conduct of this Department that we should obtain the services of a well-trained physician with broad clinical experience and a wide knowledge of the practice of medicine.” He recommended Louis Marshall Warfield ( Johns Hopkins ’97, M.D. ibid. ’01), stating that “his experience in the practice of medicine and as a consultant assures us a broad type of approach in the problems of medicine.” Dr. Warfield’s appointment began in 1922, and he continued to serve as Professor of Internal Medicine and head of the Department of Internal Medicine until 1925. He was not happy in his position at the University, however, because of certain changes occurring in the School and because of various controversies which had arisen, both before and after his arrival in Ann Arbor. He resigned in 1925 and returned to his practice in Milwaukee. Warfield was followed by Preston Manasseh Hickey (’88, M.D. Detroit College of Medicine ’92), Professor of Roentgenology, who kindly consented to be temporary administrative head of the department until a suitable successor to Warfield could be appointed. James Deacon Bruce (M.D. Detroit College of Medicine and Surgery ’96) was Director of the Department of Internal Medicine for the years 1926-28. He resigned to become the Director of Postgraduate Medicine and Vice-President of the University in charge of University relations. During his directorship of the department, the Tuberculosis Unit was started, an allergy service was developed, and the Simpson Memorial Institute was built. Frank N. Wilson Internal Medicine (1942) 17

The Period Since 1927

The present Director of the Department of Internal Medicine and Director of the Thomas Henry Simpson Memorial Institute for Medical Research is Cyrus Cressey Sturgis (Washington ’13, M.D. Johns Hopkins ’17). Before coming to Michigan in 1927 as Professor of Medicine and Director of the Simpson Memorial Institute he was a member of the faculty of the Harvard Medical School and physician of the Peter Bent Brigham Hospital in Boston. The last year that Dr. Bruce was Director of the Department of Internal Medicine, there were twenty-eight members of the staff — a director, two professors, three assistant professors, eight instructors, one instructor in dietetics, four research assistants, one assistant, and eight interns. During the following year, 1928-29, the medical staff was increased to three professors, four assistant professors, fifteen instructors, eight senior interns, and eight junior interns, a total of thirty-eight. All members of professorial rank of the original staff were retained, with the exception of John Barlow Youmans (Wisconsin ’15, M.S. ibid. ’16, M.D. Johns Hopkins ’17), who resigned to accept an assistant professorship in internal medicine at Vanderbilt University. Among the additions to the professorial staff of the department in 1928 was Charles Leonard Brown (Oklahoma ’19, M.D. ibid. ’21), who had been an instructor in the Harvard Medical School. He came to the University as Assistant Professor of Medicine. The Department of Internal Medicine had previously been divided into several services, consisting of a service in metabolism headed by Dr. Newburgh, a cardiology service under the directorship of Dr. Wilson, a private medical service which had been directed by Dr. Bruce, and a tuberculosis service under the directorship of George Alexander Sherman (McGill ’19, M.D. ibid. ’24). During the year 1928-29 Sturgis combined the cardiology, metabolism, and private medical services with those of general medicine. This allowed Newburgh, Wilson, and their staffs ample opportunity to continue with the excellent experimental work that they had 18 Internal Medicine

done in the past and which they had found difficult to continue because of the heavy clinical load they were required to carry. John Blair Barnwell (Trinity College ’17, M.D. Pennsylvania ’23) was brought to the department as Director of the Tuberculosis Unit in November, 1928. He had been research instructor in pediatrics at the University of Pennsylvania, and a fellow and acting first assistant of the rudeauT Foundation. With the addition of the special branches of medicine to general medicine it became necessary to reorganize teaching on the various medical wards. In order to facilitate handling the large number of students at that time, the medical service was divided into four general medical services, a medical outpatient service, a private medical service, a tuberculosis service, and a diabetic outpatient service. The work of the students was divided equally among the four services. They devoted half of their time to the medical section on the wards, and each group alternated between two instructors. The other half of the time in the medical section was spent in the private medical service, the tuberculosis service, the diabetic outpatient service, and the medical outpatient service. The new arrangement allowed more individual attention for each student and more cases for the student to examine than had heretofore been possible. The general medical services were also reorganized so that each attending man who taught the senior students was a member of the permanent staff and of professorial rank. His assistant was a third- or fourth-year staff member of the rank of instructor who also taught the junior section in the afternoon. Each ward was under the direction of an assistant resident and an intern. Better care of ward patients was possible, and teaching for both the student groups and the younger staff men was more comprehensive and individual. The department by 1940 had a staff of fifty-one members — three professors, six associate professors, five assistant professors, seventeen instructors, three research fellows, one instructor in dietetics, nine senior interns, and seven junior interns. The large staff made it possible to provide postgraduate instruction for the younger members. Interns were selected, who, if they were satisfactory, could be given a total of four years’ training in internal medicine. Such an opportunity for Internal Medicine (1942) 19 postgraduate training greatly increased the number and quality of men who applied for internship in the department. In the early period of Dr. Sturgis’ directorship of the department it was difficult to obtain men of the first rank for appointment to the intern staff. The situation changed greatly, until in 1937 sixty- five applications were received for seven internships; many of the applicants were in the first 10 per cent of their respective classes, and most of the best medical schools in the country were thus represented. During the first thirteen years Dr. Sturgis was Director a number of the younger men were appointed to professorial positions elsewhere. Dr. Wilson, Dr. Newburgh, Dr. Paul Shirmer Barker (Westminster ’15, M.D. Washington University ’20), Dr. Henry Field, Jr. (Syracuse University ’16, M.D. Harvard ’20), Dr. Herman H. Riecker (Marietta College ’17, M.D. Johns Hopkins ’23), and Dr. Arthur Covell Curtis (’23, ’25m), all members of the earlier medical staff, were still active in the department as of 1940. In addition to providing the routine teaching of medical subjects the department has doubled the length of the courses in clinical microscopy and physical diagnosis, and numerous elective courses are offered to students interested in the various special phases of general medicine. The Department of Internal Medicine teaches more hours a year than does any other department in the Medical School. That such teaching has not been burdensome to students can be seen in a statement in “A Criticism of the Teaching at the University of Michigan Medical School by the Class of 1935”: “In general, we feel from the standpoint of teaching, that the Department of Internal Medicine is outstanding in the Medical School…” Several services of the department benefited during the thirties, either by new accommodations, marked growth, or special grants. Two additional floors costing $250,000 were erected on top of the Hospital to serve as a new unit for the care of patients with pulmonary tuberculosis. The floors were first occupied by patients in July, 1931. Accommodations were provided for ninety-eight patients in six single-bed rooms, ten two-bed rooms, and seventy-two four-bed rooms. Ample 20 Internal Medicine

teaching rooms and workrooms for examinations, treatments, laboratory work, and fluoroscopy are also available. The allergy service has slowly grown from a part-time interest of one man in 1927 until it occupies three rooms on the second floor of the Hospital and has a permanent staff of three men and, in addition, one man part time. The diabetic service has likewise slowly grown until now it has entire care of all diabetic patients assigned to the department and also supervises the care of all diabetic patients on services other than the medical service. It was found possible in 1936 to rotate the senior instructors who were members of the medical service, in periods of a month each, through the electrocardiographic service, the allergy service, and the Simpson Memorial Institute. This allowed these men to spend all of their time for the period in pursuing the special work given in the three divisions and greatly added to the training that they received. In 1937 one million dollars was appropriated from the Horace H. Rackham Fund, the interest on which was to be used for a period of not less than five years and not more than ten years, for the study of arthritis. This work was organized in the University Hospital under the directorship of Dr. Richard Harold Freyberg (’26, ’30m). Arthur C. Curtis

SELECTED BIBLIOGRAPHY

Adams, Charles K.Historical Sketch of the University of Michigan. Ann Arbor: Univ. Mich., 1876. Announcement, Department of Medicine and Surgery [Medical School, 1915 — ] (title varies), Univ. Mich., 1850-1940. Boelkins, Richard C.”A Brief History of the Department of Internal Medicine in the Medical School of the University of Michigan.”Proc. Victor Vaughan Soc., Univ. Mich., Vol. 8 (1937). Breakey, William F.”The Department of Medicine and Surgery in the Fifties.”Mich. Alum., 7 (1901): 265-77. Bruce, James D.”The Department of Internal Medicine.”Mich. Alum., 32 (1926): 518-20. Calendar, Univ. Mich., 1871-1914. Catalogue …, Univ. Mich., 1848-71, 1914-23. Internal Medicine (1942) 21

MS, “A Criticism of the Teaching at the University of Michigan Medical School by the Class of 1935,” Univ. Mich. Dock, George. Letters in MS correspondence. Univ. Mich. Dock, George. “The Medical Library of the University of Michigan.”Mich. Alum., 13 (1907): 240-48. Farrand, Elizabeth M.History of the University of Michigan. Ann Arbor: Register Publ. House, 1885. Ford, Corydon L.”Memorial Address on Alonzo Benjamin Palmer.”Physician and Surgeon, 10 (1888): 245-53, 297-302, 355-60. Hinsdale, Burke A.History of the University of Michigan. Ed. by Isaac N. Demmon. Ann Arbor: Univ. Mich., 1906. “An Historical Sketch of the Department of Medicine and Surgery of the University of Michigan.”Med. News, 78 (1901): 605-12. Memorial Meeting for Victor Clarence Vaughan … (Univ. Mich. Offic. Publ., Vol. 31, No. 35 [1930]). Memorial of Alonzo Benjamin Palmer. Cambridge: Riverside Press, 1890. [News notes.]Mich. Daily, Oct. 21, 1891; Oct. 1, 1908. MS, “Minutes of the Medical Faculty” (title varies), Univ. Mich., 1850-1940. Novy, Frederick G.”The University of Michigan Medical School, Ann Arbor,”Annals Int. Med., 9 (1936): 1035-42. President’s Report, Univ. Mich., 1853-1909, 1920-40. Proceedings of the Board of Regents …, 1864-1940. Shaw, Wilfred B.The University of Michigan. New York: Harcourt, Brace and Howe, 1920. University of Michigan Regents’ Proceedings …, 1837-1864. Ed. by Isaac N. Demmon. Ann Arbor: Univ. Mich., 1915. Vaughan, Victor C.A Doctor’s Memories. Indianapolis: Bobbs- Merrill Co., 1926. [2]

Internal Medicine (1975)

Fred J. Hodges

The Department of Internal Medicine, first officially so-called in 1908, was preceded in the history of the Medical School by professorship appointments variously designated as “The Theory and Practice of Medicine,” sometimes including pediatrics, pathology, and other disciplines. Dr. Cyrus Sturgis served brilliantly and effectively as chairman for thirty-two years until his retirement in 1959. His last years were marked by failing health, necessitating the designation of one of his outstanding professorial colleagues, Dr. Paul Barker, as Acting Chairman until the chairmanship was filled by the appointment of Dr. William Robinson in 1958. The Sturgis era in Internal Medicine was marked by splendid patient care, brilliant teaching at all levels, and research performance of high quality. The Simpson Memorial Institute for hematologic research, of which Dr. Sturgis was director, was well recognized nationally for its research in blood diseases, particularly pernicious anemia. Established individually in suitably equipped quarters Drs. Harry Newburgh and Frank Wilson endowed the Department of Internal Medicine with a Internal Medicine (1975) 23 research output unmatched by any other clinical department of the Medical School. Dr. Newburgh’s field was nutrition, Dr. Wilson’s was electrocardiography. Dr. Wilson’s introduction of chest leads which made possible the discovery and localization of myocardial infarcts is in standard widespread use throughout the world today. His intensive mathematical study of the electrocardiogram led to complete reversal of the earlier-held understanding of the dextrogram and the levogram in man. Newburgh found experimental proof for nutritional concepts by placing hired volunteer human subjects within fully controlled environmental rooms for weeks at a time. In the latter part of this thirty-year period the staff in Internal Medicine has been very materially increased in numbers, and the number and variety of research activities has undergone corresponding increase. Through representation on the Executive Committee, Internal Medicine has exerted strong influence in the development of Medical School policy and practice. [3]

Internal Medicine (2016)

Joel D. Howell

One of the oldest departments at the University of Michigan, now the largest department in the University, the Department of Internal Medicine is generally regarded as one of the leading internal medicine departments in the United States. Faculty teach at all levels of the Medical School and University, conduct an impressive amount of cutting-edge research, and offer a wide range of clinical services. The Department is consistently top- ranked by U.S. News & World Report (in 2016, the Department was ranked sixth in the nation). Numerous Department faculty members are regularly inducted into prestigious academic honorary societies. Leadership of the Department over the period covered by this history has been provided by the following chairs: Internal Medicine (2016) 25

William D. Robinson 1958-1975

William N. Kelley 1975-1989

Tadataka Yamada 1990-1996

H. David Humes 1996-2000

Laurence F. McMahon (interim) 2000-2001

Marc Lippman 2001-2007

Robert Todd III (interim) 2007-2008

John Del Valle (interim) 2008-2009

John Carethers 2009-present

It’s important to note at the outset of this overview that any attempt to write a history of a department this large and diverse cannot hope to be comprehensive. Many outstanding achievements, important programs, and key groups (such as the associate chairs, for one) go unmentioned. Financial structure and management, while critically important for departmental functioning, is not addressed. What follows is a discussion of overall changes in the Department from 1970 to the present, followed by the history of each of the divisions. Like most major U.S. internal medicine departments, the Department grew rapidly following the conclusion of World War II in 1945. Much of that growth was made possible by an exponential increase in federal funds available for extramural research, largely from the National Institutes of Health (NIH), although for the first few decades the Department was not particularly aggressive in pursuing such funds. In at least one instance the chair refused an offer of additional NIH support on the basis that they had enough funds already. Nonetheless, here and elsewhere increasing numbers of faculty were spending increasing amount of time doing scientific, often laboratory- based research. The Department entered the 1970s with William Robinson, a rheumatologist, as its chair. Departmental members could look back on a long track record of significant accomplishments. But they did so from a Department that while still having significant strengths (most notably in endocrinology, nuclear medicine, and rheumatology) was perceived by many as having become 26 Internal Medicine

excessively inbred and declining in terms of productivity and national stature. Especially worrisome was that this decline was occurring precisely when the national prestige of internal medicine was on the rise, when around the country the specialty was drawing the best and brightest medical school graduates. While most of Michigan’s units were regarded as among the best in the country, the Department was barely in the top half of U.S. departments. This perception changed rapidly after the 1975 arrival of William N. Kelley to succeed Robinson as chair. Kelley was, like Robinson, a rheumatologist. His selection came despite significant questions about his ability to lead the Michigan Department. Some saw his young age – 35 – as a source of concern. Others pointed out his relatively limited administrative experience; he had been the chief of a relatively small division at Duke, with only a handful of tenure-track faculty members. However, Kelley’s arrival ushered in an era of fundamental change and brisk growth. He led the Department with a forceful style as he set out to make Michigan the “Harvard of the Midwest.” Because he entered a department in which most scientific faculty had trained at Michigan, Kelley sought to recruit faculty from outside of the institution. (Clinically-based faculty were more often hired from within.) In the 1980s alone, the number of Department faculty expanded from 148 to 233. The influx of mostly-junior new hires had the net effect of making the average faculty age younger; annual progress reports from the 1970s and 1980s included the average faculty age, which declined from 45 in the late 1970s to 40 by 1988. (The decision to include the average faculty age in the annual report is itself a telling signifier of the importance placed on recruiting a younger group of faculty.) New faculty needed incremental laboratory staff and space. As a result, the overall size of the enterprise, both in numbers of people (which included not only faculty but also research support staff at all levels) and overall budget increased at an even greater pace than the number of faculty alone. Between 1975 and 1989, the Department budget grew from $2 million ($8.93 million in 2016 dollars) to $39 million ($75.56 million in 2016 dollars). The Department Internal Medicine (2016) 27 became much more aggressive at seeking research funding. This grew from $2.2 million ($9 million in 2016 dollars) in 1976 to $10.7 million ($27 million in 2016 dollars) by 1980. And growth continued. Research almost doubled between 1985 and 1990 alone (from $21.7 million in 1985/86 ($48.45 million in 2016 dollars) to $42.6 million in 1989/90 ($82.53 million in 2016 dollars)). Prestigious new programs arrived, most notably in 1983 the Howard Hughes Institute for molecular genetics. It not only included support for eight new faculty positions, most of which went to faculty in Internal Medicine, but the very fact that Michigan was capable of competing for it served as an indicator of the rising status of the Department. Recruitment of each successful faculty member made it easier to recruit the next one. Many of the faculty recruited to Michigan in the 1970s and 1980s became prominent national leaders. By the time Kelley left to lead the health system at the University of Pennsylvania in 1989, he had recruited 93 percent of Michigan’s Internal Medicine faculty, and the Department ranked fourth in the country in NIH funding. Subsequent chairs have successfully steered the Department through a shifting landscape and kept it in the small group of elite internal medicine departments of the country, which, given the changing world, has been no small feat. Tadataka (“Tachi”) Yamada moved from being chief of Gastroenterology to become chair of the Department in 1990. He nurtured growing strengths of the Department, in part by helping a promising geriatrics division obtain support from a Japanese pharmaceutical company. He was also able to help negotiate support for the nascent cancer center, especially from the hospital. That the Department had become seen as a national leader in basic scientific research was marked by the 1995 decision to house the editorial offices of the distinguished Journal of Clinical Investigation at Michigan for a five-year term, with Stephen Weiss as editor. By the end of his tenure in 1996, the Department received $56.9 million in NIH funding ($87.12 million in 2016 dollars). Marc Lippman, an oncologist whose scholarly work focused on basic and translational studies of breast cancer, came to Michigan in 2001 from heading the Cancer Center at 28 Internal Medicine

Georgetown University. Under his guidance, Department faculty grew from 325 to 500 and the number of endowed chairs from 15 to 28. The Life Sciences Institute was founded, with strong departmental membership. A new departmental financial model enabled more equitable distribution of funds. But even as the Department expanded, Lippman worked hard to reinforce a sense of connectivity and shared identity among Department members, in part by the creation of a society of Professors of Medicine, in part by encouraging intellectual collaborations across seemingly disparate fields. John Carethers came to the chairmanship in 2009 from being gastroenterology chief at the University of California, San Diego. Having trained at Michigan as a gastrointestinal fellow, the job felt a bit to him like “coming home.” His laboratory work focused on genetic instability in colorectal cancer. As chair he set out to improve primary care, which came under great stress following the untimely and sudden death of a beloved and extremely busy practitioner, Steven Gradwohl. Carethers not only worked to improve availability and reimbursement, but also the quality of the providers’ experiences, in part through establishment of the Steven Gradwohl Art of Primary Care Award and Workshop (named for a beloved faculty member). Endowed professorships almost tripled, from 28 to 80. We now turn to consider the Department’s role in education. In the late 1980s, Internal Medicine accounted for 19 percent of medical student contact hours in their first year of medical school (M1 year), 38 percent of student contact hours in M2, and 33 percent of contact hours for M1-M4 overall. In the early 1990s, the U-M Medical School initiated an organ- and disease- based curriculum for M2s, as well as increased clinical exposure in the M1 and M2 years, a change in which Department faculty played a central role. Training in ambulatory care has been an increasingly important element of clinical rotations for M3 students. By 1996, in lieu of a month on the wards 66 percent of all M3 students experienced a one-month internal medicine ambulatory block at University Hospital, the VA, Oakwood, and other offsite locations. The Department implemented several experimental educational programs in this time period, including instruction Internal Medicine (2016) 29 in professional counseling techniques and the ILIAD pilot program in 1990 for instruction in digitized medical information systems. A medical ethics pilot program in 1991-92 consisted of grand rounds presentations on ethical issues (such as human experimentation and patient autonomy) and monthly student conferences. In 2013, the U-M Medical School was one of 11 recipients of an American Medical Association (AMA) “Accelerating Change in Medical Education” grant, and has received $1.1 million to develop a more flexible, clinically- focused curriculum. The school’s curriculum is now undergoing a rapid and profound transformation that touches on the entirety of the four years, one in which Department members play a key role. Training in internal medicine does not conclude upon graduation from medical school. Pari passu with the post-World War II increase in size and research focus of internal medicine departments came an increasing emphasis on formal, post- medical school training in specialties, including internal medicine. (That period of training is variously referred to as internship, residency, and being a house officer.) Departmental internship and residency programs have greatly improved their status since the 1970s. At the start of that era prospective candidates were hesitant to come to U-M. They saw the program as unduly demanding and too full of routine medical chores (“scut work”). When Kelley arrived he started to make changes almost immediately. In 1976 the program initiated a daily morning report. Residents started seeing patients in ambulatory clinic for half a day per week. The program was imbued with increasing structure and sense of responsibility, as with this admonition to house staff on 3 November 1976: “If concerned or borderline patients want to be admitted – admit them. Do not question the admission or complain to the attending physician. It is far better to admit than to send the patient home and find later a wrong decision has been made.” Because the program was not seen as especially desirable, the Department would grant an interview for the house staff program to any applicant who requested one. In 1979 about 1,200 applications were received for 46 residency positions. The program improved, as evidenced in part by performance 30 Internal Medicine

on national exams. Whereas in the early 1970s only about 70 percent of the house staff passed their specialty board exams, 94 percent did so in 1979. Morale improved. During the 1980s the Department started to be seen as a more desirable location to do an internship and residency, the number and quality of applications went up, admission became more competitive — and the Department started offering applicants interviews by invitation only. By 2015, the Department received more than 3,100 applications for 44 residency positions. Cognizant of the increasing importance of ambulatory care, the Department implemented a new primary-care track in 2014. Seeing the provision of clinical care as an essential element for an academic medical school to carry out the core missions of research and teaching, in 1869 Michigan opened the first U.S. hospital to be owned and operated by a university. Ever since then the Department has played a central role in the delivery of clinical care. Of course there have been many changes in clinical activities since 1869. Some changes reflected new therapeutic techniques. Some changes were structural and organizational. Locally, attempts to improve inpatient clinical care in the 1970s were hampered by aging facilities. The existing University Hospital, innovative and forward-looking when it opened in 1925, was now well past its prime. Patients were cared for on 18-bed wards that offered little in the way of privacy. There was no air conditioning. This was a particular concern for patients suffering from respiratory diseases, some of whom worsened in the heat such that they had to leave the hospital or go into the intensive care unit. Within the intensive care unit, occasional power surges would overwhelm the electrical system. The sudden and unexpected loss of electrical power made for some anxious moments, especially for patients who could not breath on their own and were dependent on respirators. All of this made the environment a challenge for patient care, and also made it more difficult toecruit r faculty and house staff. But the physical plant was soon to change. Completion of the replacement University Hospital in 1986 marked a major milestone for the Medical School in general as well as for the Department of Internal Medicine. Improved facilities led to better and more patient care. Inpatient Internal Medicine Internal Medicine (2016) 31 admissions grew from 4,914 in 1977-78 to 7,883 in 1989-90. As the number of patients admitted rose, the number of days each patient remained in the hospital fell. At U-M, as elsewhere in the country, the goal of a hospital admission was no longer a “complete” workup. Patients didn’t remain in the hospital until every last test result had come back. Nor were patients admitted with the goal that they needed to stay until they were fully recovered. Instead, patients were discharged whenever it was possible to continue their workup or therapy somewhere else, whether at home or in a less intensive health care facility. Length of stay also decreased because new treatments for some diseases, such as myocardial infarction, allowed patients to complete their therapy sooner. The average length of stay on medicine services fell from 10.7 to 8.7 days, and has continued to decrease since then. These changes placed pressures on the educational mission of the Department, which needed to adapt ward rounds and other forms of clinical teaching to a very different tempo. Outpatient activity levels more than doubled over a decade, increasing from 51,386 visits in 1979-80 to 112,606 visits in 1989-90. People who previously had been admitted to the hospital for a procedure now had it done and went home the same day, a process expedited when the new Medical Procedures Unit was opened in 1991. In 2015 the Department counted 413,000 outpatient visits and 20,190 admissions. At the same time that patient care became more intense and pressured, national concerns over the long work hours experienced by house staff led to mandates that they work no more than 80 hours per week. These work-hour restrictions meant that incremental faculty (for whom work hour restrictions did not apply) were hired. They were hired onto a new, clinical track, one in which research and teaching were only a very small part of their lives. A key part of the Department of Internal Medicine has long been its association with the Veterans Health Administration. The Ann Arbor VA Hospital was first dedicated in 1953, and in the late 20th century it became the tertiary referral site in its VA medical center network. The associate chair for veterans affairs oversees a considerable amount of clinical and research activity. 32 Internal Medicine

In the mid-1990s, the Department benefitted from several new construction projects at the VA: a new Research Center in 1995, and a Clinical Addition Project in 1999 for general and subspecialty medicine and outpatient clinics, including a new ICU, cardiac observation unit, and other procedural suites. In 2002 a major renovation led to greatly improved space for patient care and research for the entire hospital. The VA supports physician-scientists who study a wide range of clinical and basic science areas, with strong foci of work in patient safety and health care policy. Department members at the VA Hospital are studying how best to design a hospital inpatient service with the Hospital Outcomes Program of Excellence (HOPE) initiative. Founded by Sanjay Saint in 2000, the Ann Arbor VA Medical Center/University of Michigan Patient Safety Enhancement Program was created to improve the quality of patient care through research that focuses on methods of preventing adverse patient outcomes or injuries that stem from processes of healthcare. Unsurprisingly, given the size of the Department, it played a key role in the physical growth and expansion of the U-M Health System. Many new facilities were built during this time period: the aforementioned University Hospital and Taubman Health Center (1986), the Comprehensive Cancer Center (1996), The East Ann Arbor Ambulatory Surgery and Medical Procedures Center, the Rachel Upjohn Building (including the U-M Depression Center), the Biomedical Science Research Building (2006), and the U-M Cardiovascular Center (2007). In 2009, U-M purchased the former Pfizer campus in northeast Ann Arbor, renamed it the North Campus Research Complex, and created a hub for researchers from the University of Michigan Health System (UMHS) and other areas of the University. In 2013, the Department benefitted from the first major renovation of the Taubman Center’s clinical space and the creation of an Acute Care for Elders unit at St. Joseph Mercy Hospital, and opened a new clinical site at the Northville Health Center in 2014. Education of medical students and house staff has increasingly been available at overseas locations, aided by the 2011 creation of Global REACH, in which department members Internal Medicine (2016) 33

Joseph Kolars and Michelle Heisler play key roles. Teaching and research activity is supported in China, Ethiopia, Brazil, and other countries. The Department of Internal Medicine has long been organized into divisions. One of the Department chairs’ most important responsibilities is to name the people who run each division. Every faculty member is appointed in one or more divisions, and patient care is provided in a division-based setting. The divisional structure has been fluid, with changes reflecting both internal and external pressures. In 1970 the Department was made up of 11 divisions, but General Medicine was created in 1976, Medical Genetics in 1977, in 1978 Hematology and Medical Oncology were combined into a single division, Geriatrics was formed in 1984, in 2000 the Division of Nuclear Medicine was moved into the Radiology Department, and in 2003 the Divisions of Cardiology and Hypertension combined to form Cardiovascular Disease, to arrive at the current count of 12 divisions. The size of the Department makes any attempt at a complete history implausible. What follows is, perforce, a highly selective account of activities in each division over the past five decades or so. Numbers of patients and grant dollars have gone up in all divisions, so they are generally not mentioned. Similarly, the geographic expansion of clinical sites is a common feature to all divisions, and it has also not been discussed in much detail. Readers wanting divisional data in detail should consult the “Note on Sources” below. We now turn to a division-by-division overview.

The Division of Allergy & Clinical Immunology

During the early 1970s new therapies were rapidly changing the character of medical care. Especially important for the treatment of allergic diseases was the rapid introduction of new types of steroid drugs. In 1976 division chief Kenneth P. Matthews, whose earlier work had helped to define the role of the immune system in “hives,” predicted (accurately) that patient care would change dramatically due to a long-term decrease in immunotherapy shots coupled with the rise of 34 Internal Medicine

potent corticosteroid drugs and aerosol Beclomethasone to treat asthma. In 1983 Matthews was succeeded by William Solomon, who had trained as a fellow in U-M’s Allergy Division, and who had done work on the allergenicity of small airborne particles. In 1993, Solomon recruited James R. Baker, Jr., who became chief in 1994. Baker did groundbreaking work in nanotechnology and had strong interests in non-allergic immunology, allowing the focus and name of the division to shift to the Division of Allergy & Clinical Immunology. He stepped down as in 2012 and was replaced by the current chief, James Baldwin. In the early 1990s, the Division participated in the Harvard Six Cities project, investigating relationships between indoor fungus exposure and childhood respiratory illness. With the initiation of its Core Immunology and Tissue Typing Laboratories the Division became a highly competitive choice for fellowship training. In 1999, the Division entered partnerships with the Ford Motor Company to provide care for its employees who suffered from severe asthma, and created a new Sinusitis Center (in connection with the Department of Otolaryngology) at the Center for Specialty Care in Livonia. To address the growing problem of food allergies, which have increased from affecting one in 100 children to affecting 12 in 100, in 2004 the Division created a Food Allergy Service with Marc McMorris as director. In 2007, the Division opened a new Allergy Specialty & Food Allergy Clinic at Domino’s Farms that included space devoted specifically to the Food Allergy Service. The Division has begun to develop a U-M Food Allergy Center to provide comprehensive food allergy related patient care and expand food allergy research, education and community services to help accelerate the discovery of food allergy treatments.

The Division of Cardiovascular Medicine (including the Division of Hypertension)

Prior to 2003 there were two separate Cardiovascular Medicine Divisions: Hypertension and Cardiology. Internal Medicine (2016) 35

Cardiology: 1970-2003

From 1969 to 1977 Park W. Willis was chief of cardiology. Willis was involved in early, critical studies that showed the efficacy of clot-dissolving agents in the treatment of pulmonary embolism and myocardial infarction. As division chief Willis increased the number of fellows (from four to six) and extended the length of the fellowship to two years. He also started to divide the rapidly expanding division into explicit subspecialties, a trend that would accelerate in years to come. During the early 1970s the division helped to create a new concept in clinical care delivery — geographical concentration of patients with heart disease into what is now known as a “coronary care unit” (CCU). Although these units may now seem obvious, they had to be invented. People needed to make decisions about just what would make up a CCU. One group of people made up the Michigan Comprehensive Coronary Care Project (MCCCP), which included cardiologists from the Medical School collaborating with faculty from the School of Architecture, thus taking advantage of the physical proximity of campuses at U-M. The research group explored various ways of organizing the structure in a simulated coronary care unit and published their findings in a 1973 University of Michigan Press book, Planning for Cardiac Care: A Guide to the Planning and Design of Cardiac Care Facilities. Willis was succeeded by Bertram Pitt, who had been accepted to Harvard Law School, but declined that opportunity in order to switch careers and instead attend medical school at the University of Basel in Switzerland. Pitt was recruited from Johns Hopkins to assume the Division chief position in 1977. At Michigan he continued his research on exercise testing, despite the initial difficulty presented by the exercise treadmill and the nuclear imaging device being located on different floors! The new 1986 University Hospital solved this problem. Michigan became a center for treatment of acute myocardial infarction (MI; heart attack). William O’Neil demonstrated the value of angioplasty in acute MI (it had previously been applied for patients with stable cardiac disease) and Eric Topol did path- breaking work with the “clot busting” drug tPA. Meanwhile, Fred 36 Internal Medicine

Morady did significant work on electrophysiological techniques for treating cardiac arrhythmias. Pitt stepped down as chief in 1991. William Armstrong was interim chief until Seigo Izumo arrived in 1994. He was followed in 1997 as chief by Betsy Nabel, whose work focused on gene therapy and who was the first person to successfully perform endothelial gene transfer. Kim Eagle served as interim chief from 2000 until the arrival of David Pinsky in 2002.

Hypertension 1970-2003

Sibley Hoobler headed one of the first academic divisions to focus on hypertension, and served as Division chief from 1947 to 1974. From 1974 until 1999 Stevo Julius was chief. In 1976 an Ann Arbor meeting on the nervous system in hypertension consolidated the emerging evidence that the nervous system plays a major role in the evolution and management of hypertension. Thomas Francis, of U-M’s School of Public Health, had established the Tecumseh Community Health Study in a town not far from Ann Arbor to study a wide range of health factors. Julius saw this study as a potentially valuable site to test his hypothesis about hypertension. His work there from 1987 until 1997 demonstrated that the autonomic nervous system is involved in the pathophysiology of prehypertension and the metabolic syndrome. From 1999-2003 Alan Weder served as chief of the Division of Hypertension.

Cardiology: 2003-2014

After the merger with Hypertension the Cardiovascular Division initiated many projects to study specific aspects of care, such as the Pulmonary Hypertension Service, the Women’s Heart Care Program, the Executive Health Program (in conjunction with the Preventive Cardiology Program at Domino’s Farms) and an Interventional Cardiology Program in conjunction with Foote Hospital in Jackson, MI. The Division also maintains a Hypertrophic Cardiomyopathy Program, a Peripheral Artery Disease Program, a Heart Failure Bridge Clinic Program, and a Heart Failure Service. Additionally, the Internal Medicine (2016) 37

UMHS Anticoagulation Program engaged with Blue Cross /Blue Shield of Michigan to be the coordinating center for a multi- center quality improvement initiative (MAQI Michigan Anticoagulation Quality Initiative) regarding anticoagulation therapy in the state of Michigan, thus extending the influence of the UMHS program safety practices to other institutions. The Transcatheter Aortic Valve Repair /Replacement (TAVR) Program, initially started with the designation of UMHS as one of 40 sites selected nationally to participate in the Medtronic CoreValve pivotal trial, has cultivated a close partnership with Cardiac Surgery. In 2007 Jose Jalife and Mario Delmar arrived from Syracuse, along with 33 others, to set up a center to study cardiac arrhythmias. Plans for the University’s Comprehensive Cardiovascular Center were first conceived in 1999. It became a virtual center in the early 2000s to include the disciplines of cardiology, cardiac surgery, vascular surgery, radiology (nuclear cardiology, interventional radiology, cardiac imaging), cardiovascular anesthesiology, and stroke neurology. Basic sciences (especially molecular and integrative physiology and pharmacology) were also included in the model. In 2003, U-M’s board of regents approved plans for a physical cardiovascular center, which opened in 2007. The Division relocated much of its clinical and academic operation from scattered spaces in Taubman Center and the Women’s Hospital to the new Cardiovascular Center. As the largest of its kind in the U.S., the Cardiovascular Center received favorable attention of a national audience. In 2013, the Center was renamed the Frankel Cardiovascular Center to honor donors Samuel and Jean Frankel.

The Division of Gastroenterology

In 1972 Keith Henley, a hepatologist interested in alcoholic liver disease, succeeded Marvin Pollard as the second chief of the Division of Gastroenterology (GI). That same year the return of Jorge Gumucio from Chile helped to rejuvenate the Division. Together with Milton Mutchnik and Gumucio, Henley developed a research group devoted to the study of basic and 38 Internal Medicine

translational hepatology. At this time, Henley turned his attention to develop a GI presence at the VA Hospital. The flexible fiberoptic endoscope had been invented in the Michigan gastroenterology division by Basil Hirschowitz in the 1950s and 1960s. Timothy Nostrant, who was acting chief 1981-1983, was the first person at Michigan to emphasize the importance of endoscopy and was instrumental in establishing the medical procedure unit (MPU), which today sees more than 25,000 procedures performed each year. The search for a permanent Division chief ended in 1983 when Tadataka (Tachi) Yamada came to U-M from UCLA. One of Yamada’s first initiatives was to obtain an NIH Digestive Diseases Center grant, which was crucial to the development of the Michigan Gastrointestinal Peptide Research Center in 1986. That Center was the first of its kind in the country and provided the infrastructure for Yamada to build one of the strongest GI research programs in the country, as well as one of the first to emphasize research in molecular biology. In 1990, Yamada assumed the role of chair of the Department and Chung Owyang was selected to be the next chief of gastroenterology, a position he still holds today. One of Owyang’s first initiatives was to establish a clinical Hepatology Unit, which is now one of the largest in the U.S. Phillip Schoenfeld and John Inadomi were recruited to pursue health services research for the study of gastrointestinal disease. They led an NIH grant dedicated to the training of physicians interested in clinical outcome research. The faculty’s strength in motility disorders allowed the Division to establish one of the most complete and versatile motility disorder groups in the U.S. From this group has come the first use of octreotide and neostigmine to treat chronic intestinal pseudo-obstruction; the establishment of the use of dopamine antagonists to manage gastric tachyarrhythmia; and key participation in the national gastroparesis registry. In 2000, the Michigan Peptide Center underwent a major reorganization and expansion that included more than 70 faculty members from across disciplines such as physiology, cell biology, microbiology, pharmacology and surgery. To support these activities, four major research cores were established: Internal Medicine (2016) 39 molecular biology; protein identification and localization; microbiome and host interaction; and clinical in vivo study. The Center has played a meaningful role in the academic development of individual investigators as well as the initiation of a number of program projects. For example, in the early 2000s, Juanita Merchant started collaborations with a number of Center investigators including Deborah Gumucio, Linda Samuelson and Andrea Todisco and successfully competed for a P01 grant entitled “Cellular Decisions of Differentiation in the GI Tract.” The Center was also instrumental in the development of a microbiome facility. The Division has become the second largest digestive and liver health group in the nation. The Division of Gastroenterology became the home of two major gastrointestinal journals, the American Journal of Gastroenterology and Gastroenterology. In 2009, the noted gastroenterologist John Carethers, the former chief of the University of California-San Diego School of Medicine’s Division of Gastroenterology, joined the Division when he was brought to U-M to serve as the chair of the Department of Internal Medicine.

The Division of General Medicine

The Division was said to exist “on paper” in 1976, though its full realization took a few more years. It was initially led by Jeoffrey K. Stross, who served as acting chief from 1976 through 1988. Laurence McMahon succeeded Stross as chief in January 1988 and remains in that position today. The division has been a supportive home for several interdisciplinary programs. One of the Robert Wood Johnson Foundation’s flagship programs, the Clinical Scholars Program was a fellowship program designed to integrate clinical expertise with training in program development and research methods to find solutions for the challenges posed by the U.S. healthcare system, community health, and health services research. Open to trainees from all clinical disciplines, the U- M program was based since 1993 in the Division of General Medicine, where it served as both a generative center for 40 Internal Medicine

research ideas and a training program for many U-M faculty in Internal Medicine and other departments. Led for its first 15 years by Joel Howell and McMahon, it is now under the direction of Rodney Hayward, Michele Heisler and Caroline Richardson. The Robert Wood Johnson Foundation is now phasing out support for the program (along with most similar programs), but it many of the essential elements will continue at U-M as the National Clinician Scholars Program. Established in 2010 as the merger of the Bioethics Program and the Center for Behavioral and Decision Sciences in Medicine, the Center for Bioethics and Social Sciences in Medicine (CBSSM) integrates bioethics with key social science disciplines. It does so by bringing together research, education, policy work, and public outreach. CBSSM was founded by Peter Ubel and later co-directed by Angela Fagerlin, Brian Zikmund- Fisher and Raymond DeVries. The VA Health Services Research and Development Field Program, founded in 1996 with Rod Hayward as Director, in 2007 became the VA Center for Clinical Management Research, under the direction of Eve Kerr. Her work on the promise and pitfalls of quality measurement has both documented significant gaps in health care quality and helped guide policy makers to improve. In the 1990s a group of investigators led by A. Mark Fendrick developed a health insurance model to align consumer cost sharing with the clinical benefit to reduce cost-related underuse. This concept, Value-Based Insurance Design (V-BID) has received broad support and enhanced coverage for preventive services for over 100 million Americans. The Cancer Surveillance & Outcomes Research Team (CanSORT), created in 2007, is led by Steven Katz and Sarah Hawley. CanSORT studies the quality of cancer care from prevention to survivorship. The team has also developed and evaluated interventions to improve cancer care, including decision tools for patients and clinicians and dissemination strategies to more quickly move research results to the provider community. The National Institute on Aging’s Longitudinal Health and Retirement Study is U-M’s largest extramurally funded research Internal Medicine (2016) 41 project. Associate Director Kenneth Langa is leading a study of the epidemiology and costs of chronic disease in older adults, emphasizing Alzheimer’s disease and other dementias. In 2013, John Ayanian, a general internist and health services researcher came to U-M from Harvard to lead the Institute for Healthcare Policy and Innovation (IHPI). Approved by the regents in 2011, IHPI plans to improve the quality, safety, affordability, and equity of health care by promoting interdisciplinary collaboration and engagement with public and private stakeholders. IHPI now includes over 400 members from 12 U-M schools and colleges. Members of the division carry on clinical activities in both outpatient and inpatient setting. One of the first places to deliver care away from the central Ann Arbor campus was the Brighton Health Center, started in 1982. Many other locations followed. The Division now accommodates approximately 165,000 outpatient visits at 10 clinic locations in the greater Washtenaw County area. There are an additional 40,000 VA- based outpatient visits. Nationally, a new model for patient care has been led by “hospitalists,” physicians who deliver care primarily within a hospital setting. The Department’s hospital medicine program was formally launched with the recruitment of a leader for the program in 2003. At the outset, four faculty members considered themselves to be hospitalists, all of whom worked on the inpatient ward teams with medical residents. The implementation of residency work hour restrictions resulted in the need to move some patient care away from resident teams and onto an inpatient service staffed only with hospitalists. The hospital medicine program now has over 90 hospitalists and over 20 advanced care practitioners.

The Division of Geriatric & Palliative Medicine

In the late 1970s a Geriatrics Outpatient Clinic was established, directed by Ivan Duff, to provide comprehensive interdisciplinary geriatric assessment and ongoing primary care for elderly patients. A new rotation on Medical Geriatrics started for house officers in 1982-83. The Division of Geriatric Medicine 42 Internal Medicine

was formally established with the appointment of Jeffrey B. Halter as chief in 1984. Halter served as chief of Geriatric Medicine until 2011 when Raymond Yung was appointed chief. At that time, the name of the Division was changed to Geriatric and Palliative Medicine to reflect its broader mission. The Geriatrics Center was created in 1987 to provide outstanding educational opportunities, advance research on the healthcare issues of older adults, and provide exemplary multidisciplinary care and services for the older population. The U-M Geriatric Medicine Fellowship Program started in 1981, and Margaret Terpenning, the first fellow in Geriatric Medicine at U-M, succeeded Duff as clinic director in 1985. The VA Special Fellowship Program in Academic Geriatrics began in 2001. The Geriatrics Center has received substantial funding from a number of foundations, including the W.K. Kellogg Foundation, the Donald Reynolds Foundation, and the Partners for Quality Education (via the Robert Wood Johnson Foundation). The Osher Foundation provided a $2 million endowment to support the Osher Lifelong Learning Institute of the Geriatrics Center. Another multi-million dollar initiative was funded by a collaboration of the Ministry of Health and Welfare of the government of Japan and Tanabe Pharmaceuticals to support interdisciplinary training in geriatrics for social workers, nurses, and physicians. The Institute of Gerontology (IoG) was founded in 1965 as the nation’s first state-funded center on aging. It merged with the Geriatrics Center in July 2004 with a primary goal of establishing and nurturing faculty-directed, aging-related research. The Geriatrics Center’s 2006 move to the new Biomedical Sciences Research Building provided 21,000 square feet for Biogerontology, and allowed the recruitment of four new tenure track researchers studying aging in mice, flies, and worms. Established in 1989, the Ann Arbor Geriatric Research Education and Clinical Center (GRECC) is one of 20 national centers of excellence within the VA Health Care System. Jeffrey Halter was the first director of the GRECC, which is now directed by Neil Alexander. Internal Medicine (2016) 43

The Claude D. Pepper Older Americans Independence Center (OAIC) at U-M was funded by the National Institute on Aging (NIA) as the nation’s first Geriatric Research and Training Center in 1989. The Pepper Center evolved to meet the objectives of the OAIC program, and challenges presented by Institute of Medicine reports in 1991 and 2008 calling for the development of new knowledge to improve the care of elderly people and increasing the number of health professionals to help accomplish this goal. The Nathan Shock Center for the Biology of Aging at U-M was initially funded by the NIA in 1995 and has since been successfully renewed. It is one of five such centers in the country. A Hospice and Palliative Medicine Fellowship Program was started by the Division in 2007, and in 2009 became one of the first American Council for Graduate Medical Education (ACGME)-accredited Palliative Medicine Fellowship Programs in the United States. The Division provided leadership and organizational oversight to a newly-structured Palliative Care Service, a collaborative initiative of the Departments of Internal Medicine, Family Medicine and the University Hospitals.

The Division of Hematology/Oncology

In 1978, the Sections of Hematology and Medical Oncology were combined into a single Division of Hematology/Oncology under the leadership of Albert LoBuglio. After the departure of LoBuglio in 1982, Beverly Mitchell was named acting chief, followed by the appointment of Max Wicha in 1983. Wicha had come to U-M in 1980 after completing his fellowship at the National Cancer Institute. His initial research laboratory in the Simpson Memorial Institute Building was located in a converted women’s lavatory. A sign on the door said “Women Only,” perhaps making it a propitious place for Wicha to start his fruitful research career in the field of women’s cancers. Wicha served as Division chief until 1992, when he was named director of the Cancer Center. Robert Todd III served as chief from 1993 until he became interim chair of the Department in 2007 and Kathleen Cooney became chief. Cooney moved to 44 Internal Medicine

the University of Utah to become chair of internal medicine in 2016. Pavan Reddy now serves as interim chief. Wicha’s first major recruit was David Ginsburg from Harvard. Ginsburg is now a professor in the Division of Molecular Medicine & Genetics (where his work is described; vide infra). Research highlights of the division include major advancements in regional chemotherapy, radioimmunotherapy, apoptosis mechanisms, and early genetics studies. Todd’s research focused on the functional characterization of membrane receptor gylcoproteins expressed by human inflammatory and neoplastic cells. The recruitment of Laurence Baker from Wayne State University in 1994 was integral to increasing the Division’s focus on clinical research. Baker established a Clinical Research Program that was able to meet the growing needs of clinical investigators, including the establishment of a Clinical Trials Office and the formation of the Protocol Review Committee. Major clinical research findings included the demonstration of significant long-term efficacy of hepatic artery fluorodeoxyuridine and conformal radiation therapy for the treatment of hepatobiliary and colorectal cancers; significant molecular and genetic advancements (e.g. BRCA2, Bcl-x, p53) related to breast and prostate cancers and hematology; and advances in chemoprevention related to colorectal cancer. Mark Kaminski and Richard Wahl reported in the New England Journal of Medicine that the treatment of chemotherapy-refractory B- cell lymphoma patients with radiolabeled anti-CD20 antibodies resulted in high response rates and durable complete remissions, and later the invention of tositumomab, a monoclonal antibody that was efficacious in the treatment of patients with follicular lymphoma. In 2005 Baker became chairman of the Southwest Oncology Group (SWOG), the largest clinical trials organization in the world, and SWOG headquarters moved to Ann Arbor. Significant research discoveries in the 2000s included further understanding of biomarkers; the advancement of therapeutic clinical trials for the treatment of genitourinary cancers, gastrointestinal cancers, head and neck cancers; the establishment of anti-cancer drug discovery program with a Internal Medicine (2016) 45 team of computational and medicinal chemists, biochemists, structural biologists, cell and tumor biologists with the goal of creating “designer drugs” to target aberrant signaling pathways in cancer cells; major advancements in the identification and characterization of stem cells with the target of molecular profiling and therapeutic interventions; a paradigm shift in the field of bone marrow transplant immunology by the characterization of the molecular pathogenesis of acute graft- versus-host disease; and advances in chemoprevention research including the development of novel therapeutic strategies to prevent colorectal, cervical, and esophageal cancer. During the mid-1980s, Divisional outpatient care was held in a combined clinic in the Med Inn Building. The Infusion Center was held in a cramped room with five infusion chairs. Because there were no electronic records, the room held high stacks of patient charts documenting the multiple cycles of chemotherapy. The University of Michigan Comprehensive Cancer Center was established in 1986. The administrative offices had been housed in two portable trailers behind the Simpson Building until the new state-of-the-art center was finally built in 1997. Once moved into the new building, clinical ‘teams’ were established to align resources around specific disease areas. A substantially larger infusion unit allowed Division members to do a much better job managing patients’ treatment needs. In 1995, the Division added a 16-bed Bone Marrow Transplant Unit and a Medicine Chemotherapy Service for the treatment of patients on scheduled chemotherapy needing additional clinical coverage. Bone marrow transplants saw a ten-fold increase 1991 to 1999. Clinical activities nearly doubled from 2000 to 2010.

The Division of Infectious Diseases

Robert Fekety founded the Division of Infectious diseases in 1967. In the 1970s the U-M Departments of Microbiology, Pediatrics, the Divisions of Allergy & Immunology and the School of Public Health began to develop relationships in infectious disease research. New research techniques allowed the framing of critical questions about mammalian [host] 46 Internal Medicine

interactions with microbes. Fekety’s work provided important early insight in antibiotic-associated diarrhea. The incidence of pseudomembranous colitis had increased dramatically soon after antibiotics were introduced in the 1940s, but the cause remained unclear. Fekety’s group did one of the key early studies in identifying Clostridium difficile as the cause of antibiotic-associated pseudomembranous colitis. In the 1980s, the Ann Arbor VA Infectious Diseases Section Faculty (Carol Kauffman, Suzanne Bradley, Dennis Schaberg) and many of the Division’s Fellows (Nancy McGuire, Alfred Bacon, Carol Chenoweth, Joan Duggan, Preeti Malani, Shelly McNeil, Hector Bonilla, Sara Hedderwick, and Anurag Malani) conducted pioneering studies of how older adults responded to infection and how the clinical aspects of various infections differed with aging. They studied the risk factors for colonization and infection with antibiotic-resistant microorganisms and the transmission of these organisms, including methicillin-resistant Staphylococcus aureus, high-level gentamicin-resistant and vancomycin-resistant enterococci, and fungi within the nursing home setting. Fekety was followed as chief by N. Carey Engleberg in 1994. The Division became more specialized over time in response to growing needs, with some of the impetus to change coming from inside the institution, and some from outside. Powel Kazanjian was recruited from the Brigham and Women’s Hospital to head the AIDS Program in 1995. In 1996, the University Hospital program obtained federal Ryan White Funding for patient care. In 1997 a program was started to restrict antibiotic use. Kazanjian became chief in 2005. A new transplant program in 2005 helped the solid organ transplant programs (lung, liver, kidney, pancreas, heart) and bone marrow transplant programs establish treatment protocols for treatment and prophylaxis of infection. Because a largely educational approach to use antibiotics rationally failed to reduce antibiotic overuse and stem the increasing epidemic of drug-resistant organisms the division established the Antimicrobial Stewardship Program in 2010. In 2012, Michigan became an epicenter for an epidemic of Internal Medicine (2016) 47 spinal meningitis, due to complicating spinal injections of a contaminated steroid preparation. Kauffman assumed a national leadership position, providing guidelines and recommendations on the diagnosis and the optimal combined medical and surgical treatment of these infections.

The Division of Metabolism, Endocrinology & Diabetes (MEND)

Jerome Conn, discovered primary aldosteronism, the curable cause of hypertension whose syndrome bears his name. Conn was chief of the Division, then known as Endocrinology and Metabolism, from 1943-1973. In 1973 Stefan Fajans became chief. Fajans is best known for his demonstration that Maturity- Onset Diabetes of the Young (MODY) is a type of diabetes distinct from juvenile-onset diabetes ( JOD or type 1 diabetes), and similar to maturity-onset type diabetes found in middle age or older groups (MOD or type 2 diabetes). He described a family with MODY in 1964, and in 1991 was able to identify genetic markers for the condition. The identification of MODY helped to establish that within known types of diabetes there are various subsets of the disease. In 1977, U-M was awarded a grant to create the Michigan Diabetes Research and Training Center (MDRTC), one of the first five institutions in the country to receive such funding. The activities of the MDRTC initially were organized into three categories: research programs; training and demonstration programs (the Diabetes Care Unit); and continuing education programs. The three main research foci in the late 1970s were basic cell regulation, natural history and genetics of diabetes, and management and treatment of diabetes. Beginning in 1983, U-M participated in the largest, most comprehensive diabetes study ever conducted — the 10-year Diabetes Control and Complications Trial (DCCT). A clinical study funded by the National Institute of Diabetes and Digestive and Kidney Diseases, the DCCT showed that keeping blood glucose levels as close to normal as possible slowed the onset and progression of eye, kidney, and nerve disease caused by type 1 diabetes. U-M was also one of the first medical centers to 48 Internal Medicine

study insulin pumps as alternative delivery systems for insulin among type 1 diabetes patients. In 1987 John C. Marshall was named Division chief. Edward Schteingart, who established an adrenal cancer program and an obesity clinic, was interim chief from 1990-1991. Douglas Greene became chief in 1991. In 1997, researchers from the U-M Medical Center and the Veterans Administration Medical Center in Ann Arbor published two important diabetes studies — one showing that people who develop type 2 diabetes at an early age can substantially reduce their rates of blindness and kidney failure by tightly controlling their blood sugar level, and another indicating that it is extremely difficult for people with type 2 diabetes to control their blood sugar through conventional use of insulin. Green stepped down in 2000, and Roger Grekin became interim chief. Grekin held several leadership positions in the Ann Arbor VA Healthcare System and was a beloved medical educator who directed the M1 and M2 curriculum for many years. In 2003, Peter Arvan became chief and brought his seven- member team from the Albert Einstein College of Medicine in New York City to the University of Michigan. The Division’s name was changed in 2005 to the current name: Metabolism, Endocrinology, and Diabetes (MEND). Division member Arno Kumagai launched a new educational initiative, the Family Centered Experience, designed to give medical students direct experience with people living with chronic diseases, including many with diabetes. In 2005, The Michigan Comprehensive Diabetes Center (MCDC) was created to unite all diabetes-related academic activities on the University campus. Arvan was named as its director. The MCDC includes six research centers: the Michigan Diabetes Research and Training Center, Michigan Metabolomics and Obesity Center, JDRF, Animal Models of Diabetic Complications Consortium and Clinical Diabetes. Later, the Brehm Center for Diabetes Research was added with the opening of the Brehm Tower, an innovative, new $132 million, 222,000-square-foot facility that houses the Brehm Center for Diabetes Research, along with an expansion of the W.K. Kellogg Eye Center. Internal Medicine (2016) 49

The Division of Molecular Medicine & Genetics (MMG)

In 1974, Thomas Gelehrter, a physician-scientist interested in regulation of enzyme activity in mammalian cells, joined the Department of Human Genetics with a joint appointment in the Department of Internal Medicine. In the late 1970s, Gelehrter and Roy Schmiekel (Pediatric Genetics) began seeing patients in an outpatient clinic and in 1977 Gelehrter became the first Division chief for a new division of Medical Genetics. Gelehrter recruited Francis Collins and Andrew Feinberg, to join the division. Collins then became chief from 1987 to 1991. It was at U-M that Collins began his research toward the successful sequencing of the human genome. In 1989 his studies led to the identification of the genes that cause cystic fibrosis. In the early 1990s, Collins left U-M to join the National Institutes of Health and become the director of the National Human Genome Research Institute. (He would become director of the Institutes in 2009). At the time of Collins’s departure, James Wilson, an expert in gene therapy approaches, became chief from 1991-1993 and changed the name of the Division to Molecular Medicine & Genetics. Following the departure of Wilson in 1993, Ginsburg became chief from 1993-2002 and switched his primary appointment out of the Division of Hematology/ Oncology. Major research advancements during the 1990s included the use of transgenic mice and knock-out mice to conduct research in genetics and molecular therapeutics. Ginsburg did seminal work on bleeding and clotting disorders, especially the molecular mechanism underlying von Willebrand disease, thrombotic thrombocytopenic purpura (TTP), and combined factor V and factor VII deficiency. In 2002, Stephen Weiss became chief of the Division. Weiss recruited faculty emphasizing work on genetic and molecular approaches to development, differentiation, and survival in normal cells and in disease states, especially cancer. The Division was able to grow its clinical activity in the cancer genetics area, in part due to the appointments of a number of key genetic counselors as clinical track faculty members in the Department (Victoria Raymond and Jessica Everett), and in 50 Internal Medicine

part as a result of support provided and interactions established by the Division with a number of key faculty who hold appointments outside of the Division, including Elena Stoffel and John Carethers in Gastroenterology and Ralph Stern in Cardiovascular Medicine. The research activities of the Division also grew as the result of a new model where the Division jointly recruits and co-invests in the start-up packages of junior faculty who pursue research that is closely aligned with the MMG Division, but who wish to continue to practice in the Internal Medicine Division that is aligned with their specialty training and boards. Eric Fearon, who works on the molecular mechanism of cancer pathogenesis, became chief in 2010.

The Division of Nephrology

John Weller, a general nephrologist whose work focused on electrolyte metabolism and hypertension, was the first division chief for Nephrology, starting in 1964. The Michigan Kidney Registry (MKR) was started in 1969 by Ronald Easterling. MKR became the first statewide end stage renal disease (ESRD) registry in the U.S. When Easterling left U-M in 1979, John Weller became MKR’s director. One example of important early work done using this database was to account for time-to- treatment bias while comparing dialysis versus transplant survival — at that time a novel approach. When Weller retired in 1994, Fritz Port became MKRs new director. In 1988 a national ESRD registry was established via funding from the National Institute of Diabetes Digestive and Kidney Diseases (NIDDK), resulting in formation of the United States Renal Data System (USRDS). The goals of the USRDS are to characterize the ESRD population, identify trends in mortality and disease rates, investigate relationships among patient demographics, and provide data sets and samples of national data to support research. The first contract was awarded to the Urban Institute in Washington, D.C., which subsequently collaborated with researchers at the University of Michigan Kidney Epidemiology and Cost Center (UM-KECC). When Philip Held, an economist, was recruited from the Urban Institute to U-M in 1993, the USRDS coordinating center was Internal Medicine (2016) 51 moved to U-M. It organizes information about the treatments and outcomes of the 13 percent of Americans who suffer from chronic kidney disease, providing clinical, biostatistical epidemiological, data management, and analytic expertise. For a time the USRDS Coordinating Center left U-M; it returned to U-M in 2014. Friedrich Port was division chief from 1977-1978, followed by Richard Tannen from 1978-1988. Tannen brought more of an emphasis on cellular and molecular biology and recruited faculty who focused their research on the basic sciences. In 1987 Josephine Briggs established how kidneys autoregulate blood flow to the nephrons. She later went on to head the NIDDK Division of Kidney, Urologic and Hematologic Diseases. Roger Wiggins (chief from 1988-2004) continued the emphasis on basic understanding of kidney diseases, especially diseases of the glomerulus, and was one of the first to specifically study the unique function and regulation of the podocyte, the glomerular epithelial cell that is critical for blood filtering. Both basic and translational kidney science discoveries have been made by several younger investigators. Benjamin Margolis’s work led to a better understanding of epithelial polarization, a characteristic of cell surfaces that is important for regulating the movement of fluids, while Matthias Kretzler studied cellular mechanisms involved in renal failure. In 2014 James Shayman, a nephrologist trained in lipid biology, saw the end result of a four-decade collaboration with the late Norman Radin, a neurochemist, when the FDA approved Cerdelga as a treatment for Gaucher disease type 1. Gaucher’s disease is an inherited disease that affects many organs of the body and affects more than 10,000 patients worldwide. Prior to Shayman’s discovery of Cerdelga, treatment was difficult, expensive, and had limited efficacy. Cerdelga solved many of those problems. The U-M sold a portion of its worldwide royalty interest in Cerdelga for $65.6 million in 2014. Attention to improving outcomes for African Americans with hypertension, renal disease, and kidney transplants was led by Akinlolu Ojo, who was director of clinical and translational research in the Comprehensive Kidney Center. Ojo led a multinational research effort to uncover genetic factors in 52 Internal Medicine

kidney disease in sub-Saharan Africa. His research and clinical interests include chronic kidney disease and kidney transplantation and their complications, including cardiovascular disease; pharmacotherapy of hypertensive and diabetic renal disease; minority health and health disparities; global health (non-communicable diseases in low-resource settings); and global health capacity development. He has a particular clinical interest in chronic kidney disease in developing nations.

The Division of Nuclear Medicine

William Beierwaltes, the first chief of nuclear medicine, started one of the first nuclear medicine fellowships in the country. He studied the role of radiopharmaceuticals in the diagnosis of adrenal disorders and the treatment of thyroid cancer. David Kuhl, who came to Michigan in 1985, continued his path breaking work on positron emission tomography. He became chief in 1986 and helped to build a division with notable strengths in evaluation of neuroendocrine tumors and metastatic cancer using PET, and in the treatment of thyroid cancer and B-cell lymphoma. The Division of Nuclear Medicine moved to the Department of Radiology in 2000.

The Division of Pulmonary & Critical Care Medicine

John G. Weg was recruited from Baylor University in 1971 to head the division. It was called the Medical Chest Section until 1971, the Pulmonary Division from 1971-1974, and the Division of Pulmonary and Critical Care Medicine since then. Weg spearheaded the Division’s involvement in major multicenter trials, including the PIOPED trial, which led to improved understanding of how to diagnose pulmonary embolism. Joseph P. Lynch, III, was named acting chief in July 1985, and served in this role until the recruitment of Galen B. Toews in July 1987. Toews served as chief of the division until his untimely death in October 2011. Theodore J. Standiford became chief of the division after oeT w’s passing. The 1970s and early 1980s were characterized by pulmonary physiology research centered on gas exchange and Internal Medicine (2016) 53 thromboembolic disease. Much of this work was performed in the dog lab located in the old Kresge Building. Human clinical research included seminal observations of gas exchange abnormalities and oxygen uptake in obliterative pulmonary vascular disease and in patients with ARDS. Toews recruited and nurtured a group of outstanding faculty members with expertise in cell and molecular biology, and forged strong collaborative ties with investigators in the Department of Pathology. Particular areas of expertise included lung innate and acquired immunity, acute lung injury, and pulmonary fibrosis. The early to mid-1990s were marked by the development of disease-focused translational research programs in interstitial lung disease, chronic obstructive pulmonary disease (COPD), acute lung injury and lung transplantation. The translational research programs in interstitial lung disease (ILD) and chronic obstructive pulmonary disease (COPD) were greatly enhanced by the 1991 recruitment of Fernando Martinez. Led by Robert Strieter and Steven Kunkel, ARDS research at Michigan studied the cellular and molecular processes responsible for the pathogenesis of acute lung injury. Health services research blossomed in 2008 with the addition of Theodore ( Jack) Iwashyna. Iwashyna assembled a research group that uses the tools of social-science research to investigate short- and long-term outcomes of severe sepsis, as well as to study the quality and organization of health services in the intensive care unit. The Medical Intensive Care Unit (which was supervised by the chief medical residents) and Respiratory Intensive Care Unit (which was supervised by pulmonary faculty) merged in the summer of 1982. The first “modern” pulmonary function lab was established in the early 1980s. Considered state-of-the-art at the time, the lab included a large water-filled tank that used an inverted cylinder to measure volumes quite accurately. The lab could perform up to eight pulmonary function tests per day. With the addition of many more beds — first at the new University Hospital in 1986, then at the new Ann Arbor VA Medical Center in 1998 — there was an explosion in critical care at the institution, including a major focus on sepsis, acute 54 Internal Medicine

respiratory distress syndrome (ARDS), acute respiratory failure, and acute liver failure. The division developed clinical programs to meet the needs of the local and statewide community. From its inception, the care of patients with tuberculosis (TB) was a central focus. A physician widely respected for his clinical acumen, Robert Green, was passionate about the study and treatment of TB. He served on the Washtenaw County Health Department TB Advisory Board from 1963-1972, and was the physician in charge of Washtenaw County’s TB clinic for twenty years, as well as serving on many national committees. He later became interested in geriatric medicine, and joined the Division of Geriatric Medicine in 1992. Richard Simon has provided consultation for TB in non-human patients, specifically surveillance bronchoscopies for a 42-year old African rhinoceros at the Detroit Zoo. (The rhino never developed active disease). Established in 1990, the Lung Transplant Program at Michigan grew rapidly, with 837 transplants being performed in 580 patients between 1990 and 2013. The 44 transplants done in 2013 placed U-M in the top fifteen of lung transplant centers nationally. The Pulmonary Rehabilitation Program was launched in 1998 at Domino Farms as a necessary component of the National Emphysema Treatment Trial (NETT). The first NETT patient was enrolled on April 13, 1998, and she went on to survive for an additional 15 years. When fiber optic bronchoscopy was introduced at the University in the early 1970s, the procedure was performed only in the inpatient setting, in a small utility room without nursing support. The first bronchoalveolar lavage was performed in a patient with sarcoidosis by Joseph P. Lynch III in 1980. Lynch started the Interstitial Lung Disease (ILD) Program in the early 1980s, with an emphasis on sarcoidosis and idiopathic pulmonary fibrosis (IPF). A dedicated Sarcoidosis Clinic, headed by Eric White, came to fruition in July 2011. The Adult Cystic Fibrosis (CF) Program experienced tremendous growth, becoming one of the top CF Centers. Richard Simon, director of the Center since 1994, also served on the CF Foundation Internal Medicine (2016) 55

Advisory Board and led the Foundation Drug Safety Monitoring Board overseeing clinical trials in CF.

The Division of Rheumatology

When the Rackham Arthritis Research Unit was founded in 1937, supported by a $1-million grant from the Horace H. Rackham Fund, it was one of only a handful of units in the U.S. dedicated to research in rheumatologic diseases. The Arthritis Division within the Department was founded in 1960, and the two units merged into a single division under Giles Bole in 1976. (The name was changed to the Rheumatology Division in 1984). Bole moved into the dean’s office in 1986 as senior associate dean; he subsequently served as dean from 1991-1996. Irving Fox was interim chief from 1986-1988. Thomas Pelella served as chief from 1988-1990. He was succeeded by David Fox. In the early decades of the Rackham Unit key areas of study included rheumatoid arthritis, gout, biology of synovial tissue, and basic studies of glycosaminoglycans and glycoproteins. Bole, Sarah Walker and others began to focus on systemic lupus erythematosus (sle) research in the late 1960s and early 1970s, exploring the connection between the use of oral contraceptives and clinical manifestations of lupus. They also began to explore the effect of immunosuppression in animal models of lupus. With the arrival of W. Joseph McCune in 1983, clinical research on humans with lupus began to accelerate. In 1988 McCune published a landmark New England Journal of Medicine paper describing a novel approach to the treatment of lupus. Monthly intravenous infusions of cyclophosphamide were shown to be effective for patients with severe lupus involving kidneys, brain, and other organs, even in those whose disease was worsening despite high dose corticosteroids. Since then, tens of thousands of lupus patients have been treated using this protocol. Basic research on autoimmune mechanisms related to lupus has been led by Bruce Richardson. In the late 1980s Richardson first observed DNA hypomethylation in T-lymphocytes in patients with active lupus, and over the 25 years since he has explored and amplified these findings. This landmark advance was the first delineation of the importance of epigenetic mechanisms 56 Internal Medicine

in autoimmune diseases. The Department has also conducted research in the fields of rheumatoid arthritis, scleroderma, vasculitis, inflammatory myopathies, fibromyalgia, and a wide range of autoimmune diseases. Through the 1980s, in addition to serving as chair of the Department, Kelley maintained an active research laboratory in the Division. He and his colleagues (including Thomas Pallela, James Wilson, Beverly Davidson and Blake Roessler) accomplished a series of steps leading to the first proof of concept of gene therapy in vitro and also in vivo in mice. Meanwhile, one of Kelley’s earliest trainees, Irving Fox, had been recruited to the faculty of the Division of Rheumatology in 1976. Fox directed the University of Michigan Clinical Research Center during a period of rapid growth. His laboratory was responsible for improved understanding of purine enzyme pathways. In an important New England Journal of Medicine paper in 1987, this group also described the connection between cyclosporine and gout in the transplant population. Gary Nabel was recruited to the Division of Rheumatology in 1987 as an investigator supported by the Howard Hughes Medical Institute.. He developed an important research program, unusual in its scope and depth with accomplishments in the areas of gene regulation, gene therapy for cardiovascular disease (in collaboration with his wife Elizabeth Nabel, a cardiologist) and gene therapy approaches to malignancy. In 1999 Nabel left Michigan and became the founding director of the Vaccine Research Center at the NIH. In addition to individual research project grants, research in the Division of Rheumatology has been supported over the years by a variety of center grants. The Multipurpose Arthritis Center grant was first awarded in 1977, and funding continued with a subsequent change in the name of the center to the Multipurpose Arthritis and Musculoskeletal Diseases Center, until the program was phased out by the NIAMS in 2000.

Conclusion

As the University enters its third century, the Department of Internal Medicine is larger and more diverse than ever before. Internal Medicine (2016) 57

There are 392 clinical faculty, 271 instructional track faculty, and 91 research track faculty. Total grant funding approaches $78 million. The total budget has risen to a projected $272 million in 2017. The sheer size of the Department poses problems both for those who seek to administer it and those who seek to write about it. For most of its existence the Department has had to confront a panoply of challenges, and today is no exception. The Medical School curriculum is being radically transformed. One of the major functions of the Department — the training of house staff in Internal Medicine — is being restructured almost daily, with changing restrictions placed on the amount of time that can be spent seeing patients. Partly as a result of these limitations, the faculty is increasingly made up of physicians who spend most of their time not in education or research but in direct patient care, on a track separate from the instructional academic track. (Over half of the faculty have been employed on the non- instructional track since the mid-2000s). Delivery of primary care is becoming increasingly important and increasingly difficult. Within the University, departments negotiate their position within an increasingly prominent array of organ and disease-based centers (cancer, cardiovascular, etc.). The extramural research funds on which much recent growth is based seem to have slowed, leading to inevitable financial tensions. The United States continues to spend an ever- increasing proportion of its GDP on health care, to a level that would soon appear to be unsustainable (though that observation has been made many times before). Nonetheless, the tasks confronting the Department are no less real and no less compelling that they were in 1970 or before. Faculty members train the next generation of physicians, seek to create new knowledge, and deliver patient care. Michigan’s Department has done so in a manner befitting the top departments in the country for the past several decades, and is likely to do so for some time.

Note on Sources

Choices had to be made about what to include in this history. 58 Internal Medicine

For readers wanting to know more about any part of it, here are some of the essential sources on which this document is based and places one could go to find more information: For primary sources, the essential starting point is the Bentley Historical Library in Ann Arbor, which houses a plethora of manuscript material related to the Department, the Medical School, the Hospital, and much else. The Regents’ Proceedings are located there, as well as in searchable form online. The Bentley web site offers an introduction to a large quantity of material available on the web. The Department’s annual reports contain a wealth of information, but they change considerably over time, which makes tracing trends sometimes difficult. However, the 2015 Annual Report is focused on the history of the Department, and has considerable material including reminiscences of chairs, timelines of key events, and much more. Each division provided information about its history. These documents contain a wealth of material that could not be included here, and can be found at the departmental web site. Useful published sources include:

Horace W. Davenport, Not Just Any Medical School (Ann Arbor: University of Michigan Press, 1999). Joel D. Howell, ed., Medical Lives & Scientific Medicine at Michigan, 1891-1969 (Ann Arbor: University of Michigan Press, 1993). Joel D. Howell. U-M’s Rackham Arthritis Research Unit. Michigan Medicine 88, January 1989: 36-38. Kenneth Ludmerer, Let Me Heal: The Opportunity to Preserve Excellence in American Medicine (Oxford: Oxford University Press, 2014). Richard D. Judge, Eric R. Bates, and Kim A. Eagle, One Hundred Years of Excellence: 1891-1991. A History of Cardiovascular Medicine at the University of Michigan. (Ann Arbor: Historical Center for the Health Sciences, Monograph Series Number 6, 2001).