Chapter  Th e Castleman Era (1952–1974) David N. Louis and Robert H. Young

r. Benjamin Castleman was a dynamic She remembered, with particular fondness, Dr. Dand focused individual, and the Castleman Oliver Cope, who had been from a Pennsylvania years were of a similar nature for the department: Quaker background and with whom her hus- dynamic in that much of Dr. Castleman’s cha- band had had a long and close friendship as well risma was conveyed to the department, invoking as working relationship. Dr. Mallory himself had a sense of a “golden era”; and focused in the sense taken a relatively large number of Jewish physi- that the department clinical services included cians as residents, including Dr. Castleman, and only anatomic pathology (autopsy, cytopathol- was known as a very tolerant individual; his clos- ogy, and surgical pathology). est assistant, Edith Parris, was African American. Th e transition to Dr. Castleman as chief was Regardless, the appointment was a signifi cant also diff erent from the prior two leadership tran- one: Dr. Castleman became the fi rst Jewish Chief sitions. Both Drs. Wright and Mallory had come of Service at MGH. from “the outside,” whereas Dr. Castleman had As mentioned, the department had a scope been in the department since his rotation as a under Dr. Castleman that diff ered from the Yale medical student, and he had been in the breadth under Drs. Wright and Mallory. Th e department as its fi rst true pathology resident clinical laboratories had already migrated away and then as a faculty member. Moreover, he had from functional Pathology involvement. More- served as Acting Director for two years during over, in 1952, at the start of Dr. Castleman’s ten- World War II, and for a year after Dr. Mallory’s ure, Bacteriology was split away from Pathology death—becoming the offi cial chief of the depart- and incorporated into the Infectious Diseases ment in 1953. Th us, the transition to Dr. Castle- Division of the Medical Services, which had man was less of an upheaval than that from Dr. grown markedly as a specialty in the early anti- Wright to Dr. Mallory. biotics days that followed the close of World War Dr. Castleman’s appointment was notable II. Th e Blood Bank remained, as it had since its in another way, because he was Jewish. He had inception, in Surgery (see below). Th us, Pathol- grown up in a religious household and had, at ogy during the Castleman era was “Anatomic one time, studied with the famous Rabbi Joseph Pathology”—a focus actively encouraged by Dr. Soloveitchik of Boston. Anti-Semitism certainly Castleman himself, who saw anatomic pathol- existed in the hospital, but Anna Castleman (in ogy as the true calling of the pathologist. Indeed, 2009) recalled that physicians from the estab- although he facilitated training of pathology lished Boston families were not anti-Semitic. residents in clinical pathology to conform to the

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growing requirements of the American Board of and Cytogenetics, and each of those experienced Pathology, he required residents rotating in clini- major growth. cal pathology to participate in the two major ana- Th e Castleman years also witnessed the begin- tomic pathology conferences each day and would nings of computerization and information tech- discourage pathology residents from undertaking nology, and their major eff ect on the laboratories. faculty careers relating to clinical pathology. For example, in 1965 Dr. Castleman wrote: “Th e Dr. Castleman was closely involved in all the volume of work in the cytology laboratory under clinical activities of the department as well as the direction of Dr. Priscilla D. Taft increased in the teaching of residents. As he recounted in about 10 percent during the past year. With the 1983 (1): help of Dr. G. Octo Barnett, data on each patient are now being entered in a computer. Th e pur- I personally believe that contact with one’s pose of this project is to make the diagnoses, Chief of Service is very important and I give especially those diagnosed ‘doubtful’ and ‘posi- almost two hours a day to actual participa- tive,’ more readily available for correlation with tion with my staff . . . . Th e entire staff meets at other studies in the follow-up of patients with 8:15 and for up to one hour I personally check cancer.” all the gross material of the autopsies of the Indeed, Dr. Barnett, who started the Laboratory day before. Th is is a very popular exercise and for Computer Sciences at MGH, was a pioneer in almost every morning various members of the what would become laboratory information sys- clinical staff , both house and members of visit- tems and played a major role in the development ing staff , appear to take part when their case of multiple computer systems in the laboratories is coming up. Every afternoon from 2 to 3, I over the next few decades. For instance, in 1966 personally check the interesting and problem he implemented MUMPS (MGH Utility Multi- microscopic slides of the surgical pathology Programming System) in the Chemistry Labora- specimens that have come through that day. tory, enabling it to be the fi rst hospital laboratory Th ese two hours each day give me an opportu- in the nation to be computerized. nity to actually know what is going on in the Nostalgia for the Castleman era continues to department and also give an opportunity to this day, as alumni wax eloquent about “BC” the various members of the department, who and the vigor he brought to the department. Th e are working on research problems or who are interested reader is encouraged to view the hour- assigned to bacteriology, hematology, or chem- long Alpha Omega Alpha Leaders in Medicine istry to return to the laboratory each day in the video of Dr. Castleman being interviewed shortly morning before they start their regular work before his death in 1982 (www.alphaomegaalpha. and right after lunch before they start their org/leaders.html). Th e interview by Dr. Ronald afternoon’s work. Weinstein gives one an idea of Dr. Castleman’s It was also a period of signifi cant growth. In personality, convictions, and interests. He burst 1951 there were 7 faculty, 7 clinical trainees, and with pride at what his trainees had done, both 20 nonprofessional employees; by 1972 there in going on to prestigious positions in academic were 15 faculty, 21 trainees, and 65 nonprofes- pathology and in endowing an annual United sional employees. In that time surgical specimens States and Canadian Academy of Pathology increased from 9,752 to 20,546 a year and autop- (USCAP) award in his name. One gets the sense sies from 687 to 952 a year. New clinical labora- that he was a demanding but highly eff ective tories began in the department, notably Cytology Chief of Service.

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Laboratories Space remained a critical problem in the early Castleman years. In 1952 some research space was opened up on the fourth fl oor of the Domestic Building, suffi cient for the Histochemistry Labo- ratory and the research laboratory of Dr. Agnes S. Burt (Russfi eld). Th e Histochemistry Labo- ratory, under Dr. Edgar Taft, used this space to work with the new Linderstrom-Lang cryostat to develop better techniques for rapid tissue prepa- ration, and Dr. Robert Fennell used the labora- tory to continue his studies of cervical cancer pathogenesis and cytology-histology correlation. Clearly, Pathology needed new clinical space, but funding had not been suffi cient to com- mence planning until 1953, when the hospital’s Building Fund had grown large enough for the Trustees to authorize the design and construction of the new building. It was expected that ground would be broken in 1954. Edgar Taft, at that time one of the Assistant Pathologists, devoted about half of his time to planning for the new building. Dr. Castleman complimented him for his “excel- lent ideas and resourcefulness. He has been an excellent liaison between the staff and the admin- Figure 7.1 Artist’s sketch of the Warren Building istration, the architect and various manufacturers at the time of its opening, in a brochure of equipment.” Indeed, given that many of the for the opening ceremonies administrative and anatomic pathology compo- nents of the department still reside in the Warren which occurred under the tenures of Drs. Robert Building in 2011, Dr. Taft’s input in this regard Colvin and David Louis in the 1990s and early has been felt for decades. 2000s. It is worth noting, however, that such plan- Th e groundbreaking for the Warren Building ning pertained only to anatomic pathology and (although it was at the time called the Medi- related research, since the clinical laboratories, cal Science Building) took place on November Blood Bank, and Bacteriology resided outside the 8, 1954 (fi gure 7.1). In this year the family and department. Th is physical split of the anatomic friends of Edwin S. Webster, a former hospi- from the clinical laboratories was in eff ect carved tal Trustee, raised funds to set up the Edwin S. in bricks and mortar at this time, and the divide Webster Laboratory in the new building, which would remain through the rest of the twentieth would be in the basement and devoted to the century, only to begin to be remedied with the new technology of electron microscopy. A grant integration of the anatomic and clinical labora- was obtained from the NIH to purchase the fi rst tories that was planned to follow the integration electron microscope, a second grant was obtained of the anatomic and clinical pathology faculty, in 1959 to acquire a second one, and a third was

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Figure 7.2 Plot plan of the MGH, 1956, indicating the Figure 7.3 A Boston Globe article about the Warren location of the Warren Building (upper left) Building published on December 3, 1956

purchased in 1965. Th e laboratory would con- ceremony for the opening of the Warren Build- tinue as an integral part of the department for ing was held on December 3, 1956 (fi gure 7.3), decades, expanding when it moved into the Cox attended by numerous dignitaries, including Dr. Building in 1976; it was closed unoffi cially with Wilder Penfi eld, the noted neurosurgeon from the move of Pathology out of the Cox Building Montreal. Th e Right Reverend Robert P. Barry, in 2000. in his comments at the dedication, spoke elo- With construction having started in 1954, Dr. quently about the hopes that rested on the activi- Castleman could write with nostalgia about the ties in the new structure: “Th e building not only Allen Street Building (see fi gure 5.1), comment- houses the marvels of modern scientifi c equip- ing that his annual report for 1955 would be “the ment, brilliant doctors and scientists, but also last written in the present Allen Street Building.” your hopes and ours, that from the studies and After a review of the tenure of the department investigations that take place within its walls, in that building, he remarked, “We in the Labo- will emerge sources of knowledge to bring lasting ratory realize the high standard of the past, and benefi t to mankind.” hope that the new bricks and mortar will help us A separate gala dedication ceremony for the uphold this tradition.” Pathology department itself was held on Decem- Th e department moved into its new quarters ber 15 of that year (fi gure 7.4), when the new on September 21, 1956 (fi gure 7.2), which Dr. laboratories were christened as the James Homer Castleman referred to as “D Day,” and he noted, Wright Pathology Laboratories and the library “We could hardly wait for the paint to be dry.” A on the second fl oor as the Tracy Burr Mallory

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Library (fi gure 7.5)—both names used to the laboratories on his retirement from the Medical present day. Th e event was attended by such dig- Service in 1956. nitaries as Dr. Fred Stewart of Memorial Hospital Even in the fi rst month, the department for Cancer and Allied Diseases in New York; Dr. seemed to fi nd the new surroundings inspiring William Boyd, Professor Emeritus of Pathology even as it began to develop nostalgic feelings for at the University of Toronto; Dr. Arthur Hertig, the old building. Dr. Castleman wrote: the Shattuck Professor of Pathological Anatomy During the past month, it seems that all I have at HMS; and Captain William M. Silliphant, the heard has been: It’s about time; it was a long Director of the Armed Forces Institute of Pathol- time in coming; you certainly deserve it; what ogy in Washington, D.C. A portrait of Dr. Tracy a contrast; and many other similar remarks. Mallory, which still resides in the library—now Although we lived in the Allen Street build- alongside portraits of Drs. Castleman, McClus- ing for sixty years, we were really not unhappy key, and Colvin—was unveiled by Dr. J. Howard there. To be sure, there were no modern Means of the Medical Service (see fi gure 6.5). Th e appointments, but there was a homeliness and dedication, held on a Saturday, was preceded by intimacy that only age can bring. Th e benches a scientifi c session in which departmental faculty were always full of microscopic slides. Th ere presented their work, and many departmental was a mustiness and fl avor that seemed to alumni returned for the event. insure the correct diagnosis! Studies that have Pathology initially occupied the basement, become medical classics were carried out in fi rst, and second fl oors of the Warren Building. those rooms under James Homer Wright and An estimated 65 percent of this space was for Tracy Mallory. I trust we can carry on in their routine diagnostics: surgical pathology, autopsy, tradition. (2) neuropathology, and cytology. Th e remaining 35 percent was for research, space that the depart- And, over the fi rst year, the new building proved ment had “woefully lacked” for a long time; the a huge success: “Our fi rst year in the Warren Build- research was divided into experimental (animal) ing has fulfi lled all our expectations. . . . Routine pathology, histochemistry, microchemistry, and procedures are now carried out more effi ciently, electron microscopy. Th e research space was leading to better patient care. Th e department utilized primarily by members of the depart- is beginning to catch up with the backlog of ment, but Dr. Joseph Aub, the well-known phy- autopsy protocols and other material which had sician-scientist, joined the Pathology research accumulated partly as a result of lack of space and personnel.” Within a year of the new building’s opening, the department had about 100 members, a large department considering that it focused entirely on anatomic pathology. In 1959, when the Amer- ican Associations of Pathologists and Bacteriolo- gists and the International Academy of Pathol- ogy had a meeting in Boston, the department proudly showed off its new laboratories to the visitors—much as Dr. Wright had shown off the new laboratories when the American Association Figure 7.4 Agenda card from the Warren Building of Pathologists and Bacteriologists met in Boston dedicatory exercises, December 15, 1956 in April 1901.

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Figure 7.5 Th e Tracy Burr Mallory Library on the second fl oor of the Warren Building, at the time of its opening in 1956. Note the portrait of Dr. Mallory, which still hangs in the library.

Th e rapid growth of the Cytogenetics Labo- (adjacent to the Warren Building) beginning at ratory in the early 1960s occasioned a need for that time, the wing of the Warren Building base- more space. In 1963 the laboratory moved into ment housing the morgue and the Allen Street the Kennedy Laboratories on the ninth fl oor of entrance had to be given up, which required a the Burnham Building (eventually the Vincent new entrance to be built in the Phillips House Burnham Kennedy Building, before it was taken basement. Th is also necessitated movement of down to allow erection of the new Lunder Build- the Electron Microscopy Laboratory from the ing scheduled for 2011). Here, Cytogenetics coor- basement; one electron microscope was moved to dinated well with the nearby Neurology, Pediat- White 3 and the other, with Dr. James Caulfi eld, ric, and Gynecology services. to the Shriners Burns Institute. By the early 1970s space had once again be- By 1974 Dr. Castleman would point out that come a challenge. Dr. Priscilla Taft, writing in “the space for both patient care and research 1972, said that crowding in the Cytology Labora- activities, which has not only not increased but tory complicated hiring and retaining employees has actually decreased since we moved into the as well as storage of materials. And Dr. Castle- Warren Building in 1956, is woefully inadequate.” man added that similar conditions prevailed in He hoped that his successor as chief in 1974 would the Histology and Neuropathology laborato- garner additional space for the department, and ries, “where the volume and personnel have also he had already worked with the Search Com- increased during the past 15 years. It is hoped that mittee and the hospital administration to secure relief will be forthcoming!” additional space in upper fl oors of the Warren With construction of the Cox Building Building.

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The Pathologists Arthritis Group) and Dr. Edgar Taft (working with the Huntington Group in cancer research, Th e faculty grew substantially during Dr. Castle- “who had become nostalgic for routine pathol- man’s years as chief (fi gures 7.6, 7.7, 7.8, and 7.9). ogy”). Th e year also saw some pathologists leave, By 1966 (fi gure 7.8) the faculty had doubled to 16 most notably Dr. Louis Dienes, who retired from full-time pathologists (their distribution by their the position of Bacteriologist, which he had held HMS ranks being one professor, four associate since 1930. Dr. Winfi eld S. Morgan, who had just professors, four assistant professors, one lecturer, completed a three-year residency, left for a fellow- four associates, and two instructors). ship at Oxford, and Dr. Augustin Roque, who In July 1952 both Assistant Pathologists, had been in the department for four years help- Drs. Robert Scully and Austin Vickery, were ing develop the Histochemistry Laboratory, left called to serve in the Army—“assigned to what for additional training in London. Dr. Morgan is considered one of the best posts for patholo- would return a year later to continue his research, gists, the 406th General Medical Laboratory in and to begin a long tenure in the department (see T okyo.” Dr. Robert Fennell, who was interested below). primarily in gynecological pathology and cytol- In 1954 Drs. Scully and Vickery (chapters 9 ogy, returned from the University of Tennessee and 10) returned, both having done research on for two years to fi ll one of the opened positions, war-related issues during their time in Tokyo, and and the other position was fi lled by a combina- both became involved in the areas of pathology tion of Drs. David Kahn (doing work with the that were to characterize their interests for many

Figure 7.6 MGH Pathology, 1954. Front row, left to right: Winfi eld Morgan, Richard Cohen, Robert Fennell, Agnes Burt Russfi eld, Benjamin Castleman, Edgar Taft, David Kahn. Middle row: Raymond Justi, Gustaro Mogalon, S. C. Ming, Remedios (Rose) Rosales, Fairfi eld Goodale, Alex Ritchie, Roy Byrnes. Back row: C. Viladarez, H. Robert Dudley, Gordon LaZerte, Leonard Atkins, James Peterson.

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Figure 7.7 MGH Pathology, 1956. Front row, left to right: Winfi eld Morgan, Richard Cohen, Robert Scully, Ronald Sniff en, Benjamin Castleman, Austin Vickery, Edgar Taft. Middle row: Robert Richards, Sumner Zacks, Raymond Justi, G. Richard Dickersin, Dean Moyer. Back row: William Th urlbeck, Bradley King, Anne Th omas, Agnes Burt Russfi eld, James Davis, Martin Etchart.

decades: Dr. Vickery with the Th yroid Clinic and stories are many, but two must suffi ce here as Dr. Scully with the Vincent Memorial Group in being representative: gynecology. With their return, Dr. Fennell left Scully, while showing a case to Vickery: for Pittsburgh and Dr. Kahn for McGill. Vic [Dr. Vickery’s nickname], if you were tak- Drs. Vickery and Scully would remain with ing the board exams and saw this case, what the department for their entire long and suc- would you call it? cessful careers; along with Dr. Castleman, they Vickery: Well, I’d call it a malignant tumor would largely defi ne surgical pathology at MGH and most likely of gynecological origin. for much of the twentieth century. Particular Scully: And, Vic, what would you call it attention should be drawn to the long-term rela- when you were taking the board exams for the tionship between Drs. Scully and Vickery. Th e second time? two worked together, their offi ces very near each other, for more than fi ve decades and were close Vickery, when told by a resident at the friends; the two would direct Surgical Pathology Surgical Pathology conference that she together during the fi rst part of Robert McClus- thought the endocrine tumor looked key’s tenure. Both were superb pathologists as malignant at high power: Well, whenever I well as gentlemen—dedicated to their profes- get the urge to diagnose an endocrine tumor as sions, their colleagues, and their trainees. Both malignant, I go and lie down on my sofa until also had wonderful senses of humor, warmly the urge goes away [he had an old sofa in his recalled by all who knew them (fi gure 7.10). Th e offi ce]. My advice to you, when you are at high

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power and considering a diagnosis of endocrine pathology in London. He returned to the MGH malignancy: Get to a lower power immediately! in 1957 but left a year later for Dartmouth and then went to Albany, New York; in 1965, Dr. In the 1950s a number of other pathologists Goodale was appointed Chairman of Pathology joined the department, some only briefl y, such as at the Medical College of Virginia, and he subse- Dr. Jane C. MacMillan (1950) and Dr. Anthony quently became dean of the Medical College of C. Allison (1956–1957). Some would go on to Georgia and the Bowman Gray School of Medi- notable careers, including Drs. David Kahn cine (3). Dr. Win Morgan (fi gure 7.12) was on (1952–1954), who became Chairman of Pathology the faculty from 1952 through 1962. He was an at St. Mary’s Hospital at McGill; Agnes S. Burt accomplished researcher—one of the fi rst MGH Russfi eld (fi gure 7.11), 1954–1958, who would be pathologists to be involved in “basic” research, productive in research on the pituitary gland; working on chromatographic approaches to Fairfi eld Goodale; and Winfi eld S. Morgan. understand liver proteins—and was awarded an Dr. Goodale (fi gure 7.6), after his MGH train- American Cancer Society/British Empire Can- ing, spent 1955 to 1957 studying cardiovascular cer Campaign Fellowship in 1951 for research in

Figure 7.8 MGH Pathology, 1966. Front row, left to right: Wallace Clark, E. P. Richardson Jr., Austin L. Vickery, Ronald Sniff en, Benjamin Castleman, Robert Scully, Edgar Taft, Richard Cohen, Irwin Roth. Second row: George Kwass, John Blennerhassett, Karoly Balogh, Sheldon Baddock, Hugh Wolfe, Priscilla Taft, Martin Flax, unidenti- fi ed (higher), Jose Astacio. Th ird row: Juanito Billot, Norman Helgeson, Ronald Weinstein, Kilmer McCully, Kei Okagaki, James Daly, unidentifi ed (higher). Fourth row: Roger Williams, Joel Umlas, Virgilio Sangalang (higher), Francisco Civantos, Gerald Nash (higher), Charles Huizenga, Albert Keller (higher), Richard Jaqua, James Galdabini, John Mason (behind Dr. Galdabini), James Caulfi eld.

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Figure 7.9 MGH Pathology, 1973. Front row, left to right: James Daly, Stanley Robboy, Gerald Nash, Austin Vick- ery, Walter Putschar, E. P. Richardson Jr., Benjamin Castleman, Priscilla Taft, James Caulfi eld, Kilmer McCully. Second row: Beverly Borlander, Larry Minette, Karl Proppe, John Kaiser, Th omas Chesney, Robert Trelstad, James Galdabini, Max Goodman. Th ird row: Mark Weiss, Peter Howley, Jerry Kolins, William Cornetta, Daniel Symonds, Edwin Beckman, Jeff rey Ross, Wanda Szyfelbein. Back row: Susan Pitman, Richard Bradley, Richard Smith, Richard Geller, Anne McFarland, Jay Dubois, Walter Jung.

biochemistry at Oxford University and a Special administrative duties, including running the Fellowship from the NIH in 1958 for biochemical clinical pathology residency and helping direct research at the Wenner-Grens Institute in Stock- the MGH Research Offi ce from 1966 until his holm. Dr. Morgan left in 1963 to become Pro- retirement. He and his wife, the cytopathologist fessor of Pathology at Case Western University Priscilla Taft (see below), remained in touch with School of Medicine and Director of Pathology the department until their deaths. at Metropolitan General Hospital in Cleveland. Dr. Richard B. Cohen (fi gure 7.15) was a In 1974 he became Professor of Pathology and trainee in pathology from 1951 to 1954 and was a Director of Surgical Pathology at West Virginia member of the faculty from 1955 to 1968. He per- University School of Medicine and then served formed research on the adrenal glands and testis as chairman of that department from 1989 to with Drs. Ronald Sniff en and Fred Simmons, and 1996. he ran the innovative Histochemistry Laboratory A major addition to the department in 1952 (see below, under Research). Cohen left in 1968 was Dr. Edgar B. Taft (fi gure 7.13), who served in to become Codirector of Pathology at Beth Israel the department until his retirement in 1984, for Hospital, where he would remain until the end much of that time as Dr. Castleman’s “right-hand of his career. He was remembered by the late Dr. man” (fi gure 7.14). He performed important Harvey Goldman as “the fi nal go-to person with

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Figure 7.10 Austin L. Vickery Jr. (left) and Robert E. Figure 7.11 Agnes S. Burt Russfi eld Scully, close friends with good senses of humor

the diffi cult slide and . . . always available to chat about the case and almost any other subject” (4). Dr. Leonard Atkins (fi gure 7.16; also see chap- ter 16) joined the department in 1951 (fi rst as a trainee and then on the faculty from the mid- 1950s) and would remain affi liated with MGH Pathology for over 50 years. He did surgical and autopsy pathology in the department through the 1990s and also served as a medical examiner. Dr. Atkins did seminal work in cytogenetics. He set up the fi rst bone marrow bank to look at the use of autologous marrow in patients who had received total body irradiation or high-dose che- Figure 7.12 Winfi eld S. Morgan motherapy. Th is work led in 1959 to preparation of chromosomal spreads and to a year at the Uni- versity of Uppsala Institute of Genetics in 1962. Dr. Atkins’s pioneering development of cytoge- netics at MGH is covered in the Cytogenetics section below and in the Cytogenetics section in chapter 13. Dr. David Spiro (fi gure 7.17) was a faculty member from 1954 to 1960. He developed and ran the electron microscopy group at the Edwin S. Webster Laboratory (see above, under Labora- tories) and did research on renal ultrastructure. When he moved to Columbia University in 1960, he wrote in his letter of resignation to the Dean of HMS: “I shall always be grateful to Harvard Figure 7.13 Edgar Taft

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Figure 7.14 Benjamin Castleman and Edgar Taft Figure 7.15 Richard Cohen in the Mallory Library, late 1950s

for the privilege of having served on its faculty and working with Drs. Hertig, Castleman and many other distinguished physicians and scien- tists too numerous to mention. I therefore leave Harvard Medicine and the Massachusetts Gen- eral Hospital with great regret. However, I am looking forward to helping Dr. [Donald] McKay establish many of the Harvard ideals as regards the science and practice of pathology at Colum- bia University in New York.” Dr. Spiro trained a number of young MGH pathologists in electron microscopy, including Drs. Richard Collins and Richard B. Stenger; Dr. Stenger left in 1960 to develop an electron microscopy unit at the Uni- Figure 7.16 Leonard Atkins versity of Cincinnati. To replace Dr. Spiro, Dr. Castleman recruited become Chairman of Pathology at the University Dr. James B. Caulfi eld (fi gure 7.18) from the of South Carolina. Rockefeller Institute and the University of Kan- In 1959, Dr. Castleman recruited Dr. Walter sas in 1959. Dr. Caulfi eld did research in electron G. J. Putschar (chapter 12) from West Virginia. microscopy, studying vascular changes in diabetic He was a devoted teacher and an expert on many renal disease and in diabetic skin, and did work aspects of pathology, most specifi cally bone at the Shriners Burns Institute on preventing tis- pathology and paleopathology; he remained a sue damage after skin removal, relative to wound member of the department through 1986. In his healing and oxygen toxicity, thus addressing the early years there, Dr. Putschar infl uenced Dr. issue of pulmonary damage in burn patients. Hugh Robert (“Bob”) Dudley (fi gure 7.6), who Dr. Caulfi eld also worked with the Myocardial had joined the department in 1957. Dr. Dudley Infarction Research Unit and became pathologist specialized in bone pathology and interacted for the Atherosclerosis Center at MIT in 1971. extensively with the orthopedic surgeons. Unfor- He stayed at MGH through 1975, when he left to tunately, he died suddenly in the fall of 1961 from

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a subarachnoid hemorrhage at the age of 37, just parathyroid disease and on bone phenotypes after moving to become Chair of Pathology at in mouse experimental models with the MGH Emory University. “His sudden death shocked Endocrine Unit. the entire M.G.H. community and his many Dr. William (“Whitey”) T. Th urlbeck (fi gures friends and classmates at the Harvard Medical 7.7 and 7.19), originally from South Africa, fi n- School. Pathology has lost one of its most prom- ished his training at MGH in 1958 and focused ising teachers,” Dr. Castleman wrote. A collec- on lung pathology, spending a year in England tion of books relating to musculoskeletal disease working in pulmonary pathology research. He in the Mallory Library was dedicated in his mem- rejoined the department from 1960 to 1961 but ory; the plaque commemorating that dedication then left for McGill, where he became a full pro- remains in the library to this day, and texts from fessor in 1966. Dr. Th urlbeck went on to a distin- the collection remain in the department. guished career in pulmonary pathology, mostly at In 1962 Dr. S. Irwin Roth (fi gure 7.8), who the universities of Manitoba and British Colum- had trained at the MGH from 1956 to 1960, bia (chapter 16). returned to the department after two years at the Dr. Martin H. Flax (fi gure 7.8, and see fi gure Armed Forces Institute of Pathology; Dr. Roth’s 23.2), who had trained with David Spiro, became position at the AFIP was fi lled by another MGH a faculty member in 1960. Dr. Flax worked in pathologist, Dr. Wallace A. Jones. Dr. Roth’s experimental allergic diseases, combining light research interests remained broad throughout and electron microscopy with immunological his career, most notably focusing on squamate approaches (chapter 23). He joined the Trans- epidermis (his boa constrictor skin experiments plantation Unit in 1964 and began studies of graft were famous in the department in the 1960s!), rejection (renal, pulmonary, corneal). Dr. Flax left the parathyroid glands (initially with Dr. Castle- in 1969 to become the Chairman of Pathology at man), the cornea, and atherosclerosis. He was Tufts University. Also in the department in the a faculty member until 1975, when he became 1960s was Dr. Hubert Wolfe (fi gure 7.20), who the Chairman of Pathology at the University of was a resident from 1960 to 1964 and a junior fac- Arkansas. After spending the 1980s and 1990s ulty member from 1964 to 1968. He worked with at Northwestern School of Medicine, Dr. Roth Dr. Richard Cohen in the Histochemistry Labo- returned to MGH in 2001 on a part-time basis, ratory, initially investigating amphibian limb seg- continuing to teach residents and to work on mentation. He then studied splenic immunology

Figure 7.17 David Spiro Figure 7.18 James Caulfi eld

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Figure 7.19 William Th urlbeck Figure 7.20 Hugh Wolfe

and spent 1968 in Sir Peter Medawar’s depart- outgoing, obliging nature became well known ment in London. When Dr. Flax left for Tufts in not only in the laboratory but at the many clini- 1969, Dr. Wolfe moved with him. Both spent the cal unit meetings. We all wish him well.” In his remainders of their highly productive academic letter of resignation to the Dean of HMS that careers at Tufts. Another pathologist who moved year, Dr. Blennerhassett wrote that “it is with with Dr. Flax to Tufts was Dr. Ronald Delellis, very mixed feelings that I end my close associa- who had just completed his residency at MGH, tion with the Hospital and Medical School. Th is and who went on to an illustrious career in endo- has been an immensely valuable time. . . . It is to crine pathology and as Vice Chair of Pathology at Dr. Castleman particularly, and to the members Cornell and at Brown. of his staff and residents that I owe the greatest Dr. John B. Blennerhassett (fi gure 7.8), from debt of gratitude.” New Zealand, was a resident and fellow from Dr. James J. Galdabini (fi gures 7.8 and 7.9) 1962 through 1966; he had interests in lung, was a resident in the department from 1965 to prostatic, and gastrointestinal cancers. It was Dr. 1969 and a member of the staff from 1971 to 1981. Blennerhassett’s review of MGH autopsy records Dr. Galdabini was a superb diagnostic patholo- while still a resident that provided supportive gist who had a special interest in gastrointestinal data to the Surgeon General’s work illustrat- pathology. He served as Associate Editor of the ing the dangers of cigarette smoking (see below, Case Records from 1975 to 1981. under Autopsy). He moved to McGill University Dr. Kilmer S. McCully (fi gures 7.8 and 7.9), in 1966 but returned to MGH in 1969, when he who had been a resident in 1959–1960 and a clini- did general surgical pathology but also focused cal and research fellow from 1965 to 1968, began on renal transplantation and pulmonary disease. work in the department culturing tumor cells. Dr. Blennerhassett became Chairman of Pathol- In 1968 he joined the faculty, and, as a result ogy at the University of Otago in New Zealand of two autopsies on children with homocystin- in 1971. He was a popular faculty member, and uria, he developed a novel hypothesis linking Dr. Castleman noted in 1971: “Th e house staff homocysteine with atherosclerosis. Dr. McCully and colleagues in the department and in the hos- continued his original work in the department pital at large will miss his astute reasoning, his through 1979, when he became a faculty member infectious enthusiasm and his esprit. He had an at Brown University and chief at the Providence unusual willingness and ability to teach, and his Veterans Aff airs Hospital. Later in his career he

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moved back into the HMS system as Chief at the Other pathologists who spent relatively short Boston Veterans Aff airs Hospital. amounts of time as faculty members in the A number of trainees and faculty spent time in department in the 1960s and early 1970s, follow- MGH Pathology in the 1960s before going on to ing their training, included Drs. Victor J. Rosen careers in Boston-area hospitals. Th ese included (who went on to a career in forensic pathology, Drs. Wallace Jones (Hunt Memorial Hospital, including serving as a consultant to the Quincy, Danvers), George Kwass (Hale Hospital), Shel- M.E. TV series of the 1970s and 1980s), F. Daniel don Cooperman (Union Hospital, Lynn), Rob- Foley, Albert Keller, and Robert Hershberg. ert Harper (Memorial Hospital, Worcester), A group of trainees from the late 1950s and Lewis James (Memorial Hospital, Worcester), 1960s formed an MGH–South Dakota connec- James M. Gibson (Tufts and Memorial Hospital, tion. Dr. Karl H. Wegner trained as a resident Worcester), Joel Umlas (Mount Auburn Hospi- from 1959 to 1962. A descendant of a former tal, Cambridge), and James J. Daly (Waltham South Dakota governor and U.S. senator, he Hospital). Dr. Daly (fi gures 7.8 and 7.9) stayed returned to his home state after his training at in the department for nearly 15 years, training as MGH, where he set up a pathology laboratory a resident until 1966 and then working with the and subsequently employed two MGH trainees, Urology Service in the area of urological pathol- Drs. John Barlow and Richard Jaqua. Th e labora- ogy before leaving in 1978 to head Pathology at tory group Dr. Wegner led came to cover much Waltham Hospital. Th e department also had of the state, fl ying regularly around South Dakota pathologists join from Boston-area hospitals; and adjacent states to do frozen sections and give for example, Dr. Irwin Kline, who had directed conferences. Dr. Wegner became the Chairman Pathology at Cambridge Hospital from 1966, of Pathology and then the Dean at the University joined the department in 1968 to work on cardiac of South Dakota School of Medicine. disease; he left MGH in 1969 to direct Pathol- Many trainees and junior faculty who were ogy at Lankenau Hospital outside Philadelphia. in the department in the 1960s and early 1970s

Figure 7.21 Philip Clement Figure 7.22 Ronald Weinstein

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went on to important academic careers, includ- subsequently became Chairman of Pathology at ing Drs. Philip B. Clement, Robert B. Colvin, Baystate Medical Center in Springfi eld, Massa- Harold F. Dvorak, Gerald Nash, Jeff rey Ross, chusetts, a Tufts University–affi liated hospital. Robert Trelstad, and Ronald Weinstein. Dr. Dr. Ross (fi gure 7.9), after working at the Uni- Clement (fi gure 7.21) trained at MGH from 1970 versity of Massachusetts, became the Chairman to 1975, the last year serving as a fellow in gyne- of Pathology at Albany Medical College in 1989. cological pathology with Dr. Scully. Dr. Clement Dr. Trelstad (fi gure 7.9) was a member of the (chapter 16) went on to become a professor at the department from 1966, when he came as a resi- University of British Columbia and described a dent, until 1981, when he left to become Chair- number of new entities in gynecological pathol- man of Pathology at Rutgers University/Robert ogy. Dr. Colvin (chapters 23 and 25) focused Wood Johnson Medical School. Dr. Trelstad did on renal pathology and became Director of the research on collagen and developmental biology Immunopathology Unit following Dr. Dvorak’s and directed the pathology research laboratories departure in 1979. He became the fi fth Chief of at the Shriners Burns Institute between 1975 and Pathology at MGH, serving from 1991 to 2006. 1981. Dr. Weinstein (fi gure 7.22), who worked on Dr. Dvorak (chapter 23), an immunopathologist, red blood cell ultrastructure as well as with the rejoined the department in 1969 after two years Neurosurgical Service on research issues, became at the NIH and succeeded Dr. Flax as head of the the Chairman of Pathology at Rush University in Immunopathology Unit. After ten productive Chicago and later at the University of Arizona. years heading the unit, he left in 1979 to become Dermatopathology (chapter 18) was also Chairman of Pathology at Beth Israel Hospital, quickly becoming a departmental strength and, succeeding another MGH pathologist, Dr. David notably, was housed in Pathology rather than in Freiman. Dr. Nash (fi gure 7.9), who specialized Dermatology. In 1962, Dr. Castleman recruited in pulmonary pathology, left MGH in 1974 to Dr. Wallace H. Clark Jr., who built a strong join the University of Southern California, and dermatopathology group with an emphasis on

Figure 7.23 Karoly Balogh Figure 7.24 Max Goodman

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melanoma research. Dr. Clark left for Temple in head and neck pathology in association with University in 1969 but returned to Harvard later Massachusetts Eye and Ear Infi rmary (MEEI). in his career when he joined Beth Israel Hospital. After the “long and faithful service” of Dr. Wer- When Dr. Clark left, Dr. Joel Umlas returned to ner Mueller, in 1962, Dr. Castleman “infl uenced” the department to work in dermatopathology, but Dr. Karoly Balogh to accept the position as Direc- he left in 1970 for a long career at Mount Auburn tor of the Otolaryngology Pathology Laboratory Hospital in Cambridge and extensive local and at the Eye and Ear Infi rmary. Dr. Balogh (fi gure national work in blood banking. Dr. Martin C. 7.23) had been a fellow at MGH from 1958 to 1962 Mihm Jr., who had been in charge of research and and did research in histochemistry, particularly as teaching in dermatology at the U.S. Public Health applied to ototoxicity. He served as the primary Service Hospital in Staten Island, joined the staff ear, nose, and throat (ENT) pathologist at MEEI in 1971. Dr. Mihm wrote seminal melanoma clas- until 1968, when he moved to chair Pathology sifi cation papers with Dr. Clark. He went on to at University Hospital, affi liated with Boston publish many important papers in the fi eld and University; he subsequently moved back into to train innumerable dermatopathologists in his the HMS system at Deaconess and Beth Israel long career at the MGH (chapter 18). Hospitals. Dr. Max Goodman (fi gure 7.24), who Th e Neuropathology group (chapter 17) was had trained at the Mallory Institute of Pathology, remarkably active during the Castleman years, took over Dr. Balogh’s position at MEEI in 1968; although Dr. Castleman apparently viewed the he remained at MGH and MEEI until his death Neuropathology group as being somewhat out- in 1996. Dr. Goodman had in 1961 joined Dr. side the department and more in the purview of Bob Dudley at Emory and acted as head of the Neurology. (When one of the present authors, Emory department for a year after Dr. Dudley’s David Louis, a neuropathologist, talked with sudden death; he then moved to University Hos- Anna Castleman in 2009, she joked that her hus- pital in Boston before coming to MGH. band would be very much surprised that a neuro- Th e cytopathologists at MGH during the Cas- pathologist had been chosen to head Pathology!) tleman years were Ruth M. Graham, who served Neuropathology was directed during this time by in the Vincent Gynecology Laboratories as a Dr. E. P. Richardson Jr. (chapter 11), who joined clinical cytological pathologist from 1953 to 1956 the department in 1949 and remained active until (chapter 19), Dr. Robert Fennell and Dr. Priscilla his death, in 1998. Dr. Richardson was joined by D. Taft, who was the fi rst dedicated cytopatholo- two remarkable neurologists who were superb gist in the Pathology department, heading Cyto- neuropathologists: Drs. Raymond D. Adams pathology from 1957 to 1984. Th e Cytopathology from 1951 and Dr. C. Miller Fisher from 1955. fellowship was named after her in 1992. Th is triumvirate of neurology-neuropathology, over the next few decades, taught legions of aca- Clinical Service demic neurologists and neuropathologists. Th e Surgical Pathology list is too long to give here in full but includes Between 1951 and 1972 the number of surgical such notables as Drs. Betty Q. Banker, Elliott specimens per year increased by 110 percent, from Mancall, Henry deF. Webster, Arthur K. Asbury, 9,752 to 20,546. And, as a result of the increas- Byron A. Kakulas, Karl Erik Astrom, Richard ing volume and the increasing specialization of Baringer, and Herbert H. Schaumburg—some of the medical and surgical services, subspecialty whom joined the neuropathology staff for peri- pathology expertise grew in the department. ods of time in the 1960s and 1970s. Subspecialization had already character- Several pathologists continued to specialize ized certain services, notably Neuropathology,

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Dermatopathology, and ENT Pathology. Neuro- has need for specialists. We are fortunate that pathology, both autopsy and surgical, had been each member of our staff , in addition to being housed separately since Dr. Kubik had joined a generalist, does have a special fi eld of interest, the department in 1926. Th e 1950s and 1960s and thus most of the clinical services and their witnessed a fl owering of neuropathology under units are fairly well covered by pathologists expe- Drs. Richardson, Adams, and Fisher, the strong rienced in those specialties.” Early examples, emphasis being on medical (rather than surgical) mostly from the 1960s and early 1970s, were Dr. neuropathology, as a result of neurologists spend- Robert Scully, gynecologic; Dr. Austin L. Vickery ing one of their three clinical training years in the Jr., endocrine; Dr. Gerald Nash, pulmonary; Dr. Neuropathology Laboratory. Dermatopathology Robert Colvin, renal; Dr. James Daly, urologic; had developed under Dr. Walter Lever in the Dr. James Galdabini, gastrointestinal; and Drs. 1940s, but primarily within Dermatology rather H. Robert Dudley, Walter Putschar, and Alan than Pathology. In 1962 Dr. Wallace Clark joined Schiller, bone. Particular expertise grew around the department from Tulane University in New nearly all aspects of endocrine pathology, partly Orleans. A pathologist, Dr. Clark had already as a result of the extraordinary breadth and depth gained expertise in dermatopathology. In collab- of clinical work and research in endocrinology oration with Dermatology, he set up his research on the Medical and Surgical services at MGH. laboratory in that department, collaborating with When the highly successful endocrine pathol- Dr. Th omas B. Fitzpatrick, but he did his clinical ogy postgraduate course began in the mid-1960s work in Pathology. He held two weekly confer- (see below), the department could boast of hav- ences in dermatopathology that involved the two ing individual expert faculty to cover the thyroid departments. In 1965, Dr. Clark established the (Dr. Austin Vickery), ovary (Dr. Robert Scully), Pigmented Lesion Clinic at the MGH Tumor testis (Dr. Ronald Sniff en), adrenal (Dr. Richard Clinic, which was an important clinical develop- Cohen), parathyroid (Dr. Castleman and Dr. ment that brought together physicians from dif- S. Irwin Roth), pituitary (Dr. Agnes Burt Russ- ferent disciplines to treat and study pigmented fi eld), and thymus (Dr. Castleman). Nonethe- skin lesions. Dr. Clark was a pioneer in the fi eld less, the Surgical Pathology Service itself and the of dermatopathology (chapter 18) and began an resident rotations in surgical pathology kept all era of extraordinary clinical and research produc- these specimens unifi ed under the rubric of Sur- tivity in the fi eld. He left in 1969 to go to Temple gical Pathology until 1996—with the exception University. Th e separate hospital status of MEEI of neuropathology, cytology, and dermatopathol- set up the situation in which a specifi c patholo- ogy cases; from the mid-1970s, gynecological gist had focused on ENT pathology. Th e rela- cases; and from the mid-1980s, hematopathology. tionship between MEEI and MGH Pathology As Dr. Albert Keller, who was a resident in became closer in 1962, when Dr. Karoly Balogh the department in the early 1960s, remembered, took over from Dr. Werner Mueller; at this time the department had certain go-to guys for sub- arrangements were made for the processing and specialty diagnosis. Dr. Scully was renowned as diagnosis of tissues to be carried out at MGH, an overall superb diagnostic surgical pathologist: which continues to this day. “Bob Scully was the go-to-guy for most things, It was clear to Dr. Castleman that other areas and it was great to have someone who knew the of medicine also needed subspecialty patholo- answers! . . . Of course we went to Austin Vickery gists, both for clinical and research purposes. for thyroid, and then there was our international He wrote in the early 1970s: “Like other fi elds of star Wally Clark for skin. For bone we had Walter medicine in a large teaching hospital, pathology Putschar (to us ‘the Pooch’). He was so good, that

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I still call out from the microscope, when I use adjoining room. Th e staff consisted of six tech- one of his teachings . . .‘Th e Pooch is speaking nologists and a secretary, and 10,141 specimens to me!’ ” were processed that year. By 1966, the volume Th e subspecialized expertise drew faculty of work had increased to 17,225 specimens, members into major roles nationally and inter- and the fl oor space had been increased by nationally in defi ning and refi ning classifi ca- approximately 70 square feet. In 1971, 23,069 tion schemes—another tradition that continues specimens were processed, and 13 people now to this day. Faculty began to be involved with work in 415 square feet of space. Crowding authoring fascicles for the Armed Forces Institute exacerbates minor problems so that at times it of Pathology (AFIP) series, running committees has been diffi cult to obtain and keep person- for the World Health Organization (WHO) nel. Storage is becoming a problem because of classifi cations, and chairing and participating increased volume and lack of space. in other international classifi cation eff orts. For Th e need for separate laboratory processing example, in 1955, Dr. Castleman completed the and for dedicated faculty ensured that cytology Atlas of Tumor Pathology fascicle on tumors of would be distinct from general surgical pathol- the thymus gland, which was one of a number of ogy. And the complexity of the operation would AFIP fascicles written by members of the depart- generate the need for a laboratory information ment over the ensuing decades (see Appendix). system in 1965, as discussed above. Dr. Scully served in 1967 as chairman of the group designing an international WHO classifi - Cytogenetics cation of ovarian cancers. Th e work represented As part of his work supported by the Atomic the beginning of departmental involvement in Energy Commission to establish a bank for bone the WHO classifi cations, which also continues marrow specimens in the late 1950s, Dr. Leonard to this day (see Appendix). Atkins began to use “chromosome squash prepa- Cytology rations in search of the chromosomal abnormali- ties in various disease states.” Th e signifi cance of Once the utility of the Pap smear had been dem- the technique was quickly appreciated, and by onstrated, cytology emerged quickly as a disci- 1960 clinical cytogenetics had begun: pline of anatomic pathology sui generis (chap- ter 19). In 1960 publicity surrounding the value Because of the current increasing interest in of routine yearly cervical cytology resulted in genetics, Dr. Atkins is being bombarded with increases in the number of cervical smears exam- requests to study the chromosome patterns of ined. Nonetheless, Dr. Priscilla Taft remained the patients with congenital abnormalities, leuke- single full-time cytopathologist from January of mia and other diseases. Our association with 1957 through 1974 (when Dr. Wanda Szyfelbein the state mental institutions at Wrentham and joined the staff ). Taunton has provided him with a wealth of In 1971, toward the end of the Castleman years, material. He has just completed the study of Dr. Taft summarized the growth of Cytology, but an infant with multiple congenital anoma- also its practical challenges: lies associated with trisomy of an acrocentric chromosome; there is only one other such case In January 1957 I became director of the cytol- reported. It is hoped that further examination ogy laboratory, and the laboratory was moved of such chromosomal abnormalities may lead to from Vincent I to Warren I into 475 square feet a better understanding of the eff ect of specifi c of space, 130 in my offi ce and 345 in the large chromosomes upon the human phenotype.

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Th e service grew rapidly, quickly becoming there was input from faculty such as Drs. Castle- the largest in New England and one of the larg- man and Putschar. est in the country. During Dr. Atkins’s year and Th e autopsy fi les of the hospital—which had a half in Sweden in the early 1960s, Dr. Priscilla been so carefully kept since Dr. Wright’s ini- Taft covered the clinical duties. In 1964 there was tial eff orts to do so—proved of importance for a marked increase in service volumes, primarily research as well, most notably studies of the asso- from the Children’s Service at the hospital. By ciation between lung cancer and smoking in the 1966 the number of cases had risen to 381—251 early 1960s. In 1963 Dr. John Blennerhassett, the from MGH and 130 from other institutions; by Chief Resident, pored over the records of 5,300 1967 the number had climbed to 506. In 1969 MGH autopsies performed between 1896 and the number was 633, more than half of these 1930 and another 5,000 performed between 1956 being from outside MGH, including much of and 1961 to generate data for the U.S. Surgeon New England; the volume of material handled General. Only 17 cases of lung cancer were found was the largest in the Boston area and probably in the earlier, 35-year period, compared to 172 one of the largest in the country. Dr. Atkins cases over the later, fi ve-year period. Th e fi gures then began working with Dr. John Littlefi eld showed a tenfold increase for death secondary of the Pediatric Genetics Unit on genetic coun- to lung cancer in contrast to an only 1.7-times seling. As a result, the volume in Cytogenet- increase in deaths from all other types of cancer. ics rose further: by 1970 it was 723, 60 percent Th ese data contributed to the Surgeon General’s coming from outside. Th e following year there campaign to inform the public of the danger of were 790 specimens, cytogenetic studies on cigarette smoking, providing a powerful con- amniotic fl uid samples amounting to over 100 fi rmation of Dr. Wright’s original belief in the cases. Th us, MGH Pathology was home to one importance of these records. of the most cutting-edge approaches to genetic diagnosis, enabling a new diagnostic discipline Bacteriology to develop by applying novel technologies to a In 1952, with the retirement of Louis Dienes, the pressing clinical need. Bacteriology Unit of the Pathology Laboratory, which had been physically separate from the rest Autopsy of the department for a few years, was separated Between 1951 and 1972 the number of autopsies administratively and placed under the Infec- per year increased by more than 35 percent, from tious Disease Group in Medicine. Dr. Th omas 687 to 952. Autopsies were a huge component Paine was put in charge for a year, followed by of the department’s activities during Dr. Castle- Dr. Lawrence Kunz, who served in this role for man’s tenure, although during the later years the more than 30 years, until 1983, during a period of numbers already refl ected the downward trend extraordinary expansion of laboratory testing in that was to aff ect autopsy performance for the infectious diseases. Th e remarkable story of this next few decades. In fact, during the plateau of growth is covered in a separate chapter focusing autopsies during the Castleman era, autopsy vol- on Microbiology (chapter 21). Unfortunately, umes were on the order of 1,000 per year, peaking from the perspective of Pathology, it represented at 1,251 cases in 1963. Autopsy tissues constituted a winnowing of what had been a key part of the a large percentage of the clinical and teaching department in the Wright and Mallory years and materials, and the daily “organ recital” at eight what would eventually become a cardinal com- o’clock in the morning featured most of the ponent of Clinical Pathology. Microbiology, sub- senior pathologists along with the trainees, and sequently expanded to include all facets of the

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specialty, did not rejoin the department offi cially will become Director of Laboratories at the St. until late in Dr. McCluskey’s tenure, although Vincent’s Hospital in Worcester. Th ese liaisons residents training in Clinical Pathology rotated are helpful to the community hospital because through these laboratories during the entire time when in need of help these young pathologists that it was outside the administrative oversight of are able to bring their problems to our large Pathology. staff of experts in the pathology laboratory. Also, the MGH gains from the association Outreach because the problem cases are often referred to Dr. Castleman felt strongly that the department the MGH, and many members of our clini- should play a role in supporting pathology ser- cal staff are called in as consultants. Each of vices regionally, work that he had begun under these young men are given MGH and Harvard Dr. Mallory. As chief, he was active in developing appointments and they usually spend one day outreach activities further. As he wrote in 1962, a week in our laboratory performing a specifi c summarizing his earlier successes in the area: job and assist in teaching at the Harvard Medi- cal School. All of these activities are certainly Th e Pathology Department was one of the fi rst attractive incentives for these positions, which departments in the hospital to establish an would otherwise be diffi cult to fi ll. We are pre- association with a community hospital. In 1941 pared to continue this policy of providing any Dr. Castleman become the pathologist to the community hospital within reasonable distance Emerson Hospital in Concord, Massachusetts, of Boston with a similar service. a post that he still holds. In 1946 we undertook the pathological examinations for the Brockton Beginning in 1967, the department would Hospital and continued this service until 1959, extend the services to the Soldiers’ Home in when because of the increase in size of the hos- Chelsea. At this time the MGH-trained patholo- pital we arranged for Dr. Richard Dickersin, gists who populated regional hospitals shared who had just fi nished his residency training at diffi cult cases with the pathologists at MGH, MGH, to become their full-time pathologist. In which in turn served to provide interesting 1949, a close affi liation with the Memorial Hos- cases for residency training. Some, like Ronald pital in Worcester began when Ronald Sniff en, Sniff en, spent a considerable amount of time in one of our graduates was appointed patholo- the MGH department, teaching medical stu- gist at that hospital, where for many years we dents and residents. In 1970 Joel Umlas left to had rotated a member of our resident staff . Dr. begin a long career at Mount Auburn Hospital, Robert Harper, one of our recent graduates has while maintaining close ties with MGH, includ- just joined Dr. Sniff en as his associate. During ing continued sign-out in Dermatopathology. the war we helped a few small community hos- In 1970 the department took on the anatomic pitals, including the Lawrence Memorial Hos- pathology service of Somerville Hospital, and pital in Medford. A few years ago an association it was providing services to two additional state was established with the Beverly Hospital by institutions, the Fernald School in Waltham and appointing Dr. Robert Fienberg to our Associ- the Paul A. Dever Hospital in Taunton. By 1972 ate Staff . Th is year we have added another tie Castleman would point out that the three full- with a community hospital by arranging for time pathologists at Worcester’s Memorial Hos- Dr. Sheldon Cooperman, who has just fi n- pital were MGH alumni. ished his residency, to become pathologist to Some of these physicians maintained lifelong the Winchester Hospital. For the coming year affi liations with the MGH department. For Dr. George Kwass, an Assistant in Pathology, example, Dr. Robert Fienberg (chapter 16), upon

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retiring from the Beverly Hospital, spent many Dr. Castleman also involved the residents— years teaching residents at MGH, where he was sometimes in a not entirely voluntary way—in fondly remembered in the late 1980s for his press- the outreach activities, often asking them to do ing interest in Wegener’s “pathergic” granuloma- autopsies at outlying hospitals. Th ough they tosis. Richard Dickersin returned to the depart- were reimbursed, the reimbursement was mod- ment full-time and ran the electron microscopy est. Naturally, there were mixed responses from laboratory for many years, stepping down from the residents; some were very positive and oth- the active clinical staff in the late 1990s. ers not. As Dr. Albert Keller recalled: “We were Moreover, the outreach activities reached a poor residents raising families on $2,400 per year, signifi cant percentage of departmental cases. As so when Ben off ered the plum of $50 for doing can be seen from the following numbers, many an autopsy at Emerson Hospital, we vied for the outside cases came to MGH for processing and honor!” Others, however, felt that the process of interpretation. For example, in 1955 the break- driving to an outside hospital with autopsy tools down of MGH versus outside cases was: to perform an autopsy and then to return with fresh organs in buckets (in the back of one’s car) MGH Outside Total was something short of an honor. Autopsies 668 238 906 Surgical specimens 8,734 2,875 11,609 Teaching Cytologic smears 5,361 4,340 9,701 Dr. Castleman recognized the importance of training expert pathologists, both for the hospital By 1965 the division of MGH versus outside cases and for the discipline of pathology in general. In was: 1952 he wrote: MGH Outside Total Autopsies 970 192 1,162 It is well known that there is a great dearth Surgical specimens 13,893 2,508 16,401 of pathologists throughout the country. Th is Cytologic smears 8,134 7,678 15,812 scarcity is not because fewer men are choos- ing pathology as a specialty, but because the By 1971 the last year for which Dr. Castleman demand has increased. Most hospitals of 100 provided the breakdown in his annual report, the beds or more are seeking full-time pathologists division of MGH versus outside cases was: to be in charge not only of pathologic anatomy, MGH Outside Total but of all branches of clinical pathology includ- Autopsies 823 196 1,019 ing bacteriology, chemistry, hematology, blood Surgical specimens 17,931 2,431 20,362 bank, and cytology. Th e pathologist often is Cytologic smears 11,823 11,246 23,069 the only full-time physician in the hospital. In order to help meet this demand and to prepare Neuropathology also began long-standing men for the American Board of Pathology in associations with some of the state hospitals in both pathologic anatomy and clinical pathol- the area, such as the Myles Standish State School, ogy, the Trustees have approved a four-year resi- the Wrentham State School, and the Fernald dency program, which includes in addition to State School, and brains from these institutions pathological anatomy rotation through the vari- provided material for important studies of devel- ous clinical pathological laboratories. Th e pro- opmental abnormalities of the nervous system, gram is suffi ciently elastic, however, to enable as well as valuable materials for teaching of resi- those residents who prefer to limit themselves dents and fellows. to pathologic anatomy and research, to do so.

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Figure 7.25 Departmental conference with faculty and residents, 1956; Benjamin Castleman is enjoying the conversation.

Th us, with the length of training increased and McFarland (resident 1957–1959) recalled doing an formalized, the number of residents grew. At the autopsy on his wedding day! close of Tracy Mallory’s tenure, there had been Dr. Castleman was always extremely proud seven residents and six fellows. By 1966 there when his trainees (“the boys,” as he called them) were 10 residents, six research trainees on train- went on to achieve full professorships and became ing grants, and 10 clinical or research fellows. By department chairs. He wrote that “the laboratory 1972 there were 21 house staff , including the clin- is proud to have had a role in the training and ical residents and fellows. One of the reasons for developing of these pathologists and is obviously this growth was that Dr. Castleman himself was pleased that they have accepted these prestigious closely involved in the teaching, participating for positions” and that “we are, of course, very proud two hours each day in resident teaching confer- of the fact that 26 of our alumni of the last 25 years ences (see above). As a result, as he put it in 1961, were appointed to full professorial chairs, and “Th is personal teaching of the house staff has paid that 15 of them are or were chairman of depart- off in that applications for appointments come ments at their university.” It is unfortunately not in droves.” In addition, the residents were clearly possible to include here a comprehensive list of all dedicated to their duties, including those on the of the trainees during the Castleman era. Omit- autopsy service. Fifty years later, Dr. Robert B. ting those already mentioned as having had a role

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on the faculty, a list would include the following micro review, diagnosing from the screen! I pathologists, in approximate chronological order remember the carbon-arc projector, operated of their training and with some of their future by a resident, buzzing as you drew out the positions: Si-Chun Ming (Beth Israel Hospital, arc of electricity. He fostered such a feeling of then vice chair at Temple University); Benjamin togetherness, and that learning pathology was D. Canlas Jr. (Chair of Pathology at the Univer- a serious and honorable duty. My ideal of a sity of the Philippines); Wilbur A. Th omas (chair holiday party is still the ones given for the resi- at the University of Mississippi, the University of dents’ families by Ben Castleman—a turkey at Arkansas, and Albany Medical Center); Robert one end of the table, a ham at the other, and O’Neal (chair at Baylor, the University of Okla- resident-friends to share good cheer! homa, and the University of Mississippi); Alex- Th e holiday parties were well remembered. ander Ritchie (Chair of Pathology in Toronto); Th ey were, during the Castleman years, usually Sumner Zacks (Brown University); G. Richard held in the Mallory Library, and Dr. Castleman Dickersin (Brockton Hospital and then MGH; took pride in preparing the punch. In 2009 Anna see chapter 13); Jónas Hallgrímsson (Chair of Castleman remembered that one of the hardest Pathology at the University of Iceland); Stanley changes for her husband after he stepped down as Cohen (Chair of Pathology at Hahnemann Uni- chairman was getting used to someone else mak- versity and then University of Medicine and Den- ing the punch. tistry of New Jersey); Stanley Robboy (MGH, Th e training program itself also underwent Chair of Pathology at University of Medicine and changes over the Castleman years. With Ron- Dentistry of New Jersey, then Director of Ana- ald Sniff en, who had left the department to join tomical Pathology at Duke; see chapter 13); N. Memorial Hospital in Worcester, Dr. Castleman Scott McNutt (Dermatopathology at Cornell); set up a four-month resident rotation, both to Vivian Pinn (Howard University, National Insti- help with coverage in Worcester and to provide tutes of Health [NIH]); Alan L. Schiller (MGH general laboratory instruction for the residents. and chair at Mount Sinai in New York; see chap- And, at the MGH, given the requirements from ter 13); Peter M. Howley (NIH, then Chair of the American Board of Pathology, rotations Pathology at HMS); M. Elizabeth Hale Ham- began in 1952 in the Chemistry, Bacteriology, mond (MGH, then University of Utah), John and Hematology laboratories for those residents C. Long (MGH); John L. Farber (University of who wished training in Clinical Pathology as well California at San Francisco, NIH, and Th omas as Anatomic Pathology. Dr. Castleman encour- Jeff erson University); Philip B. Clement (Univer- aged this training, although he apparently never sity of British Columbia); Charles G. Huizenga felt that Clinical Pathology training was of the (Concord Hospital and MGH); and David Page same importance as Anatomic Pathology train- (Vanderbilt University). ing, and he discouraged the appointment of Th e attention that Dr. Castleman paid to teach- faculty-level pathologists in the clinical labora- ing was legendary (fi gure 7.25; also see fi gures 15.6 tories. Moreover, he insisted that the residents and 16.4). As Dr. Al Keller recalled in 2009: rotating through the clinical laboratories return What halcyon years! Ben Castleman was the twice daily to the department for the two key best chief ever, we were convinced: He was anatomic pathology conferences: the morning there every morning in the basement at 8 am “organ recital” at eight o’clock and the afternoon for autopsy gross review, also known as the surgical pathology conference (the “Outs” con- Organ Recital. Every afternoon at 2 he was ference). Th e Clinical Pathology training rota- in the fi rst-fl oor conference room for surgical tions underwent a number of changes over the

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a basic training in anatomic pathology and in addition join one of the research units in the department or one of the investigators in another hospital laboratory. Th e purpose of this grant is to train academic pathologists. It is of interest to compare this small group of trainees with the entire group of residents over this period; 80 percent of the 30 research train- ees are now in academic pathology, whereas 53 percent of the 70 regular house staff are in aca- demic pathology. Research fellowships were popular, and many who went on to become successful scientifi c researchers spent time in the department, learn- ing the pathological basis of disease or doing research themselves (or both), in the 1950s and 1960s. Others who did fellowships in the depart- ment had illustrious careers in academia and the government. For example, Dr. Louis Sullivan was Figure 7.26 Vivian Pinn a pathology fellow from 1960 to 1961; he went on to a career in hematology at Boston City Hospi- Castleman years and were overseen during much tal and Boston University School of Medicine, of the time by Dr. Edgar Taft. was then founding Dean at Morehouse School of Clinical fellowships blossomed during the Medicine, then Secretary of Health and Human Castleman years. For example, neuropathology, Services for President George H. W. Bush from under E. P. Richardson Jr., became a renowned 1989 to 1993, and then became President of training program, attracting high-quality aca- Morehouse School of Medicine. Vivian Pinn demic neurologists and generating seminal con- (fi gure 7.26) fi nished her pathology training at tributions to our understanding of neurological MGH in 1970, including research training in the diseases. Training for physicians and technolo- Immunopathology Unit (chapter 23). In 1982, gists in exfoliative cytopathology began in 1958 after spending some years in pathology at Tufts, under Dr. Priscilla Taft. Dr. Pinn became Chair of Pathology at How- Th at year Dr. Edgar Taft obtained the fi rst NIH ard University—only the third woman to chair Training Grant for the department, designed to an academic department of pathology and the allow trainees the opportunity to acquire research fi rst African American woman to do so. Th en, in training in association with their clinical training 1991, she moved to the NIH to direct the Offi ce in Anatomic Pathology. Near the end of his ten- of Research on Women’s Health. ure, Dr. Castleman refl ected on the importance Th e Castleman period also began the tra- of this training grant and on research training in dition, which continues strongly to the pres- general, linking time spent on the grant to the ent day, of foreign fellows rotating through the likelihood of a career in academic pathology: department for periods ranging from a month to Since 1958 we have been very fortunate in hav- a few years. Much of this would be spurred by the ing an NIH research training grant to support growing reputation of the department resulting four trainees per year. Its recipients obtain from the wide dissemination of the Case Records

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in the years following World War II, as well as Special Surgery) in New York. It was said of Dr. the increasing ease of international travel— Brooks: “Th roughout his career he was consid- which Dr. Castleman (chapter 8) and other fac- ered an excellent pathologist.” Later, the Profes- ulty took advantage of to lecture widely around sor Stanley Brooks Memorial Prize in Pathology the world. As early as 1953, Dr. Castleman wrote was established at the University of the West that six of the 96 foreign residents and fellows Indies. Another prominent guest was Dr. Vuli- at MGH were in Pathology, hailing from China, miri Ramalingaswami, the founding Chair of the the Philippines, New Zealand, Guatemala, Department of Pathology at the All India Insti- Colombia, and Brazil. In 1957 he noted visitors tute of Medical Sciences in New Delhi, who vis- from India, Brazil, and the United Kingdom. In ited a number of times. 1961–1962 he commented on nine foreign fel- Th e department also began having more senior lows, from Japan, England, Mexico, India (2), pathologists from abroad visit the department, Jamaica, Israel, Iceland, and Argentina. In 1972 such as Dr. Erwin Uehlinger from Switzerland he added up the numbers: there had been 34 fel- and Dr. Jan Mellgren from Sweden in 1958, and lows from 21 countries. One particular example Dr. Victor Harrison from the United Kindgom was Dr. Stanley (Bill) Brooks, a native of Jamaica, in 1959. By 1960 the numbers of foreign profes- who was a fellow in the MGH Department of sors visiting the department grew; they came Pathology in 1962. After training in Boston, he from the United Kingdom, India, Australia, returned to Jamaica to fi nish his training. In 1972 South Africa, Germany, Sweden, and Finland, he became Chief of Pathology at the University including Dr. Lynne Reid of the Brompton Hos- of the West Indies. He also obtained a Fulbright pital in London (who went on to become the Scholarship to study at the University of Chicago Pathologist-in-Chief at Children’s Hospital in and at the Bone and Joint Hospital (Hospital for Boston). In 1961 there were visitors from Ger- many (Dr. Erich Letterer of Letterer-Siwe disease fame), the United Kingdom, Belgium, Israel, and Iceland. Dr. Jónas Hallgrímsson of Iceland (fi gure 7.27) spent four years in the department, leaving in 1965, and eventually becoming the Chair of Pathology in Reykjavik; he maintained connections with the department over the next four decades. Th e years 1962 and 1963 saw addi- tional large groups of foreign visitors, including a second visit from Dr. Nils Ringertz of the Karo- linska Institute in Stockholm. He visited again in 1966 and published extensively in the fi eld of brain tumor pathology, including one of the early seminal grading schemes for gliomas. As mentioned above, this period also saw the increasing travel of MGH faculty to distant parts of the world to teach. Dr. Castleman felt that this was an important activity, and he encouraged the staff to travel, recording their many trips faithfully in his annual reports. He kept a detailed scrap- Figure 7.27 Jónas Hallgrímsson book of his travels that included many pictures

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of his visits to various places in the world. As he continuing in medical school, yet at a loss for described a trip of Dr. Austin Vickery’s in 1970 an alternative. to Miami, these distant teaching exercises “spread Like Peyton Rous, I was rescued by patholo- the gospel.” gists. Benjamin Castleman off ered me a year Th ese years also witnessed the establishment of independent study in his department at the of formal predoctoral, post-sophomore year fel- Massachusetts General Hospital, and Edgar Taft lowships for medical students possibly interested of that department took me into his research in careers in pathology. Th e goal was to provide laboratory. Th ere was little hope that I could medical students with the opportunity to fi nd do any investigation of substance during that out “what a pathologist actually does—some- year, and I did not. But I was riotously free to thing that a student rarely discovers.” Two stu- read and think, which led me to a new passion: dents were taken each year; they spent about molecular biology. half of their time on clinical duties and half on When Dr. Richard Cohen summarized the a research project. Th e program was initiated for activities of the Histochemistry Laboratory for HMS students, but it was extended eventually the MGH’s publication Th e News in Decem- to other medical schools; it continued into the ber 1962, he listed J. Michael Bishop among 1990s. Over the years it provided the initial train- those who had contributed to the success of the ing for many successful academic pathologists, laboratory. including some who became leaders in the fi eld. In terms of standard HMS medical student One of the fi rst two students was David Korn, teaching, Dr. Castleman estimated that approxi- who later served as an intern and resident in the mately 2,000 hours of MGH Pathology fac- department before going on to an illustrious ulty time was spent on it each year. In 1963 the career, becoming the Chair of Pathology at Stan- department began a special summer program ford, the Dean of the Stanford Medical School, for medical students, whereby seven fi rst- and Senior Vice President at the American Associa- second-year students rotated through the labora- tion of Medical Colleges, and eventually Vice tories that summer. And in 1964, with a change Provost for Research at Harvard. Another gradu- in the way third-year medical students were ate of the program who later became a chair of taught, “48 students now spend twelve weeks in pathology was Harold (Hal) Dvorak (see below). a course called ‘Introduction to the Clinic’ and Dr. J. Michael Bishop, who won the Nobel Prize each student has had the opportunity to attend for Physiology or Medicine in 1989 for the dis- 12 of our early morning conferences. Th us before covery of oncogenes, was a graduate of the pro- going on the wards each student was exposed to gram as well. As Dr. Bishop later recalled in his gross anatomical pathology, a subject that was Nobel Prize speech, he had been “rescued” by the not well covered in the past.” Moreover, once the pathologists at MGH after his fi rst two years of Health Science and Technology (HST) program medical school at Harvard: was begun in the early 1970s—a combined medi- I entered Harvard Medical School know- cal school program between HMS and MIT— ing nothing of research. But during my fi rst MGH pathologists played major roles. Alan two years there, I was awakened to research Schiller and Walter Putschar ran a course titled by new-found friends among my classmates. “Biomedical Materials” in one of the fi rst years . . . I sought summer work in a neurobiology that HST admitted students, and Dr. Schiller ran laboratory at Harvard but was rebuff ed because the HST “Bone and Soft Tissue” course through of my inexperience. My interest in practicing the 1970s. medicine declined. I became ambivalent about Major advances were made in the area of

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postgraduate medical education as well. Most An interesting and entertaining story about notably, in 1964 the department began a four- Dr. Castleman’s support of research was related day postgraduate course on the pathology of the to David Louis by Dr. David Korn. When Dr. endocrine glands, capitalizing on the remarkable Win Morgan returned from his research fellow- strengths in endocrine pathology at the hospital. ship in Stockholm, he wanted to set up a labora- Th e course was a tremendous success and contin- tory to do chromatography, which required a cold ued for many years. Within a few years, attendance room. When Dr. Morgan asked Dr. Castleman had to be limited to 50, and each year there was a for a cold room, the latter replied that it would long waiting list. Th e Case Records continued as not be a problem, that the department already a major teaching vehicle of the department. Like had a cold room: the morgue! Dr. Morgan set so many other things during Dr. Castleman’s ten- up the chromatographic apparatus in a corner of ure, they became closely associated with him. His the morgue, separated by a curtain from the area reputation as “Castleman of the CPCs” followed in which the bodies were kept, and the apparatus him wherever he went on his travels around the worked. But attempts to fi nd a technician to do world. Of note, however, is the fact that he would the research were not successful, owing no doubt be the last of the MGH Pathology chairs to direct to the macabre work environment. and edit the CPCs personally. When the department moved into its new quarters in the Warren Building in 1956, the ded- Research ication ceremonies were accompanied by a sci- entifi c session, in which faculty presented their Benjamin Castleman’s focus was on diagnos- work. Dr. Castleman was extremely pleased with tic anatomic pathology and its eff ect on clinical that occasion and with the opportunity to have care, but he recognized the importance of basic his faculty members present their research the research as well as clinicopathological research. following year to the MGH Scientifi c Advisory He clearly excelled in the latter, but he is less Committee (SAC). In this instance the presenta- clearly recognized as a strong proponent of the tions included Dr. Scully on skeletal muscle isch- former. Nonetheless, he was a strong advocate for emia, Dr. Cohen on histochemistry, Dr. E. Taft both translational and basic research—although on liver disease in rats and humans, Dr. Vickery he suggested in his writings, and his legacy has on nucleic acids and on autoradiography in thy- been, that basic research must necessarily take roid pathology, Dr. Spiro on the ultrastructure a second place to clinical excellence in a hospi- of the glomerulus in renal disease, Dr. Atkins on tal pathology department. As he wrote in 1966: the departmental bone marrow bank, Dr. Harry “Although in recent years the emphasis in many Webster on the ultrastructure of experimental university pathology departments has been on neuritis, and Dr. Alexander Kenny on parathy- the biochemical and molecular biologic aspects roid extracts. Th e SAC was laudatory: of disease, it is important to bear in mind the fact that hospital pathology laboratories have, in Th e Scientifi c Advisory Committee, in the due addition, the responsibility of patient care and course of its scheduled annual meeting, was thus the necessity of expert knowledge of ana- given the opportunity to visit the Laboratories tomic pathology. Fortunately, our department is of Pathology, and to hear presentations of some large enough to permit a balance of the research of its research activities. Th ese were impressive, eff ort with the patient-care activities so that nei- not only for their individual excellence, but also ther discipline suff ers in the training of our resi- as examples of the dynamic potentialities of dents, a situation that is not prevalent in many this, the oldest of the medical sciences. Th rough university pathology departments.” the original and appropriate utilization of

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techniques and knowledge generated by the started in 1952 as a laboratory of Pathology in younger disciplines of biochemistry, biophysics, the Domestic Building, near Bacteriology, but and physiology, Dr. Benjamin Castleman and had moved to the fi rst fl oor of the Warren Build- his associates in the Pathological Laboratories ing in 1956. Many histochemical innovations are contributing in an exemplary manner to the came from work done in this laboratory, and it resurgence of a truly experimental pathology. proved a powerful training ground for highly successful academic pathologists. For example, Along with the growth of research funding in 1964 alone, there were four fellows, including from the NIH and other agencies, grant funding Drs. Harold Dvorak, Hubert Wolfe, and John in the department grew quickly, about 20-fold Blennerhassett. in the fi rst 10 years of Dr. Castleman’s tenure. In A number of basic scientists were members 1951 research grants had amounted to $17,000, of the department during the Castleman years, whereas the total exceeded $400,000 in 1961. including Dr. Alexander D. Kenny, who joined By 1966 the department could boast that “sup- in 1957 from the HMS Department of Pharma- port for 12 research projects, 2 training grants cology and did research on parathyroid extracts; and 7 fellowships amounted to just over half a Dr. Lorna Langer (later Gilmore), who joined million dollars.” In 1972 research funds from the in 1957 from the Huntington Laboratories and National Institutes of Health, American Cancer was a steroid biochemist working on the adrenal Society, and American Heart Association were gland; and Dr. Barbara H. Sanford, who was a about $600,000. Neuropathology research blos- research fellow at MGH from 1963 to 1965 and somed during this time, as many neurologists and on the faculty from 1965 to 1972, who extended neuropathologists worked together over the next Dr. Joseph Aub’s work on cell surface diff erences few decades on a wide variety of nervous system between normal and neoplastic cells, immunoge- disorders, most notably demyelinating diseases, netics, and tumor immunity. vascular disorders, childhood diseases (this area As mentioned above, Dr. Leonard Atkins being augmented by the relationships with the began to use “chromosome squash preparations state hospitals; see above, under Outreach), brain in search of the chromosomal abnormalities in tumors, and nutritional disorders, particularly various disease states” in the late 1950s. Dr. Atkins those relating to alcoholism. Much of the work was a pioneer in both the clinical (see Clini- was directed by Drs. Raymond D. Adams and cal Services, Cytogenetics, above) and research C. Miller Fisher, in addition to Dr. Richardson. applications of cytogenetics. Th e laboratory per- A radioisotope laboratory was opened in 1959, formed early work on correlating chromosomal under the direction of Austin Vickery, primarily abnormalities with clinical phenotypes, on nor- for the study of thyroid neoplasia. In 1962 he was mal human meiosis, and on DNA synthesis. joined by E. Dillwyn Williams, a research fellow Dr. Castleman’s tenure also witnessed the from the United Kingdom; Dr. Williams went development and growth of the Immunopa- on to a distinguished career in endocrine pathol- thology Unit. Looking back in 1973, he wrote, ogy in the United Kingdom, eventually becom- “Recognizing the importance of immunologic ing Sir Dillwyn and heading the Department of thought and technology in the understanding Pathology fi rst at Cardiff and then at Cambridge and treatment of many diseases, I established University; he returned to MGH as the Putschar in 1959 an Immunopathology Unit within our Lecturer in 1988. department, designed to serve as a focus of teach- Th e Histochemistry Laboratory run by Drs. ing, research and diagnostic expertise in this Richard Cohen and Edgar B. Taft in the 1960s fi eld.” Th is laboratory group had many illustrious was a central laboratory for research. It had

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research accomplishments over the years and pathology staff attend a wide variety of service also infl uenced clinical care in a major way and specialty-unit staff meetings, demonstrating through the applications of immunohistochem- gross and microscopical material with clinico- istry, immunofl uorescence, and fl ow cytometry. pathological correlation. Each week there are Because of the long-term scope of its activities 15 to 20 such meetings. Th ree units with which in the department, including its contribution to the laboratory has a close affi liation are the clinical care since the 1980s, this unit is covered Neurology and Dermatology Services and the in a separate chapter (chapter 23). Otolaryngological Department at the Massa- chusetts Eye and Ear Infi rmary. The Close of the Castleman Years Th e neuropathology laboratory, established In his fi nal report to the Trustees in 1974, Dr. Cas- within the Department of Pathology in 1926 tleman, with characteristic humor, commented: under Dr. Charles S. Kubik and supervised “In last year’s report, which I had expected to since his retirement in 1951 by Dr. Edward be my last, I summarized the activities of the P. Richardson, Jr., was offi cially named the department during the past 25 years. Hopefully, Charles S. Kubik Laboratory of Neuropathol- my successor will be appointed before next year’s ogy in 1961. Its major activity has been to defi ne report is due!” pathologic processes in the nervous system, to His summary of most of his own tenure, writ- relate the tissue changes to clinical phenomena ten to the Trustees in 1972, is worth quoting in and to use the insights thus gained in the teach- detail, as it presents a fi rsthand overview of the ing of residents and fellows in the neurological changes that he had overseen during his years as sciences as well as in pathology. In view of its chief: prominence as a training center this laboratory has been the recipient of a training grant under Over the past 20 years the patient care activi- the National Institute of Neurological Diseases ties and the teaching program have greatly continuously since 1961, and its trainees now increased, and with our move into the Warren occupy prominent posts as neuropathologists Building the research done in the department and neurological scientists in many parts of was expanded in many directions. the United States and abroad. Among its many 1951 1972 research activities have been better defi nition Autopsies 687 952 and understanding of several white-matter Surgical Specimens 9,752 20,546 diseases of the brain including the fi rst clear Cytology Specimens 8,319 24,759 identifi cation of progressive multifocal leukoen- Cytogenetics Specimens 287 (1960) 881 cephalopathy as a distinct entity complicating Staff 7 15 neoplastic and other chronic diseases, defi nition House Staff 7 21 of the pathological histology of myelopathy in Nonprofessional Staff 30 65 pernicious anemia, and studies of cerebral dis- orders in infancy and childhood, the last made PATIENT-CARE ACTIVITIES possible by affi liation with two of the state Probably very few members of the staff real- schools for the mentally retarded. ize that the Pathology Department is closely Although dermatopathology had been interwoven with the other departments in the emphasized in the department in the 1940’s hospital. Th is interrelation, begun during Dr. by Dr. Walter Lever, a former member of the Mallory’s regime, has continued and broadened Dermatology Service, it became a more special- in scope. At the present time members of the ized unit in 1962 with the arrival of Dr. Wallace

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H. Clark, formerly professor of pathology at with those of six other Boston hospitals to form Tulane University, and a closer liaison with the a cooperative school, the Boston School of Dermatology Service was eff ected. Th e unit has Cytotechnology, which last year became associ- recently been expanded under Dr. Martin C. ated with Northeastern University. . . . Mihm, a graduate of both the Dermatology and In 1957 Dr. Leonard Atkins, under a grant the Pathology Services. Th is unit now provides from the Atomic Energy Commission, origi- teaching, consultative service, and opportuni- nated a bone-marrow bank for use in the event ties for research to residents in both dermatol- of atomic bomb casualties, and the bank was ogy and pathology as well as to residents in later used for storage of autologous marrow, the Harvard-affi liated hospitals. Th e material obtained during remission, for treatment of accumulated in the Pigmented Lesion Clinic leukemic patients. Th is involved bone-marrow developed by Dr. Clark led to a classifi cation culture and led to chromosome preparations of malignant melanoma that has now been and ultimately in 1959 to the establishment of accepted throughout he world. the Cytogenetics Laboratory. Th is unit now has In 1962, on the retirement of the pathologist a larger volume of specimens to study than any for the Otolaryngological Service of the Mas- such laboratory in the state, providing service sachusetts Eye and Ear Infi rmary, arrangements not only for the MGH, but also for most of the were made for our laboratory to process their hospitals in metropolitan Boston. Th e defi nitive surgical specimens, and one of our staff , Dr. diagnosis of mongolism, the detection of trans- Karoly Balogh, became the pathologist for the location carriers, and the fi nding of chromo- MEEI. Th is liaison has been well coordinated some abnormalities associated with congenital and provides an opportunity for our resident abnormalities have been among the practical staff to be exposed to this type of pathological aspects of the work of the laboratory. In col- material. Dr. Balogh resigned in 1968 to become laboration with the Fernald School the Cyto- pathologist to the University Hospital and was genetics Laboratory has participated in a study succeeded by Dr. Max Goodman. of amniocentesis fl uid for prenatal detection of In 1942 Dr. Joe V. Meigs and Dr. Maurice chromosome abnormalities. Fremont-Smith set up an exfoliative cytology Included in the category of patient-care laboratory under the direction of Ruth M. activities is our service to numerous community Graham in the Gynecology Service. In 1950 hospitals. Th e Department of Pathology was the Cytology Laboratory became incorporated one of the fi rst departments in the hospital to in the Department of Pathology, although it establish an association with a community hos- remained physically in the Vincent Building pital. . . . until January, 1957. At that time Dr. Priscilla D. Taft became its director, and the Cytology TEACHING Laboratory joined the rest of the Department of Teaching of the pathology house staff and fel- Pathology in the Warren Building. Service and lows in training was augmented considerably teaching are the most important concerns of the during this 20-year period. In 1952 training laboratory. Th e number of specimens processed in clinical pathology was made available by has tripled. Numerous physicians have received rotation through the Chemistry, Bacteriology, training in exfoliative cytology for periods of and Hematology Laboratories, enabling these one month to a year or more. Technicians were resident pathologists to be eligible for certi- trained under an apprenticeship system until fi cation by the American Board of Pathology 1967, when the Cytology Laboratory joined and later for positions in hospital laboratories.

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In addition to an hour-long conference every E. Scully, whose clinicopathological investiga- morning on the post-mortem examinations tions and talents in gynecological pathology are of the previous day and another conference in being acknowledged by the many invitations the afternoon on the daily surgical specimens, he receives throughout the world. A corollary there is at least one other informal teaching of our lecture tours and visiting professorships exercise every day or evening. Foreign fel- in various foreign medical schools has been to lows and medical students taking a pathology provide the opportunity in our laboratory for elective participate in these exercises. Visiting trained pathologists from foreign universities professors, many from foreign countries, give to learn our methods of training in patient-care an added fl avor and diversity to the teaching. pathology, teaching, and research. A few of In addition to monthly electives, in 1956 the these fellows became members of the resident post-sophomore fellowship was introduced, and staff , and several now hold university chairs. until the recent change in the Harvard Medical During the past 22 years there were 34 such fel- School curriculum, two to four students spent a lows from 21 countries. . . . year between their third and fourth years in the Perhaps the greatest impact of the labora- laboratory, dividing their time between patient- tory on medical teaching throughout the world care, pathology and research. Th is program has been eff ected by the clinicopathological has been one of the best methods of recruiting conferences, published weekly in the New En- medical students to enter the fi eld of pathology. gland Journal of Medicine, as the Case Records Of the 18 students who joined this program, at the MGH. Th e case method of teaching in currently 6 are pathologists, 9 are in academic medicine was germinated by Walter B. Cannon institutions, and 2 are professors and chairmen when still a medical student in the 1900’s, was of departments of pathology. With the intro- implemented by Dr. Richard Cabot beginning duction of the block system in the teaching of in 1910 and fl owered under his direction for 20 pathology at the Medical School all members of years, and was expanded to involve the entire our staff and many of our house staff have par- MGH staff and became more clinicopathologi- ticipated in teaching at HMS. A recent survey cally oriented under Dr. Mallory in the 1930’s has shown that annually about 2,000 hours of and 1940’s. During the past 20 years under teaching students are supplied by our full-time my direction the cases presented have become staff , with our house staff contributing approxi- increasingly complex in terms of both clinical mately the same amount of time. Th e members work-up and multifaceted disease entities, and of the staff participate in the many postgraduate the number of cases presented has been reduced courses given in the hospital by various clinical to one per week to allow more complete discus- services. In 1964 we introduced a course on the sion and more audience participation. . . . Pathology of the Endocrine Glands, which is Having traveled in many countries, I have given in the Countway Library and is limited seen at fi rst hand the widespread impact of the to 60 physicians. Th is course has proved very Case Records in both undergraduate and post- popular, and each year there is a long waiting graduate teaching. . . . Many of our staff mem- list. Another aspect of our postgraduate teach- bers returning from foreign travels have rue- ing is the large number of lectures and slide fully reported that they are better known for seminars that our staff members are asked to their CPC discussion than for their research! conduct at medical schools and national meet- . . . I repeat, the evidence is overwhelming that ings both in the United States and in foreign our CPCs have become a tradition and serve as countries. Th is is especially true of Dr. Robert teaching exercises all over the world.

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RESEARCH competence of the valves by Dr. Richard Kelly and Dr. Fairfi eld Goodale. Before we moved into the Warren Building in With the move into the Warren Building, 1956 the research carried on in the old Allen space for more sophisticated research became Street Building was primarily clinicopatho- available, and outside support was obtained. logical correlation and was not supported by At the present time our research funds, derived outside funds. Nevertheless, important papers from the National Institutes of Health, the dealing with the pathology of the parathyroid American Cancer Society, and the Ameri- and thymus glands, renal biopsies in hyperten- can Heart Association, amount to roughly sion, malignant lymphoma, aortic dissection, $600,000 per year, $400,000 in research pulmonary embolism and infarction, Mikulicz’s grants, $100,000 in research career develop- disease, and many others have been published ment awards and fellowships, and $100,000 from work done in our old building. Th is type in training grants. Our histochemical unit, of clinical research based on careful observa- begun in the old building, expanded, and dur- tions and often with new technics, has contin- ing the 15-year direction of Dr. Richard B. ued, with the emergence over the years of new Cohen many fellows now holding academic clinicopathological entities, such as pulmonary positions were trained in this facility. In his alveolar proteinosis, mediastinal lymph-node laboratory histochemical technics were devised hyperplasia, several distinctive ovarian tumors, for the demonstration of oxidative enzyme sys- chemodectoma of the lung, and clear-cell car- tems and applied to the study of intermediary cinoma of the vagina arising in young women metabolism. who had been exposed to stilbestrol in utero. An important addition to the research Th e last tumor is the fi rst example of transpla- facilities was the establishment of the Edwin S. cental carcinogenesis in humans. In addition to Webster Laboratory to house the fi rst electron new disease entities important advances in the microscopy laboratory for human pathology pathology and function of the thyroid gland in New England under the direction of Dr. were made by Dr. Austin L. Vickery, Jr., and of David Spiro. His fi rst major eff ort was to delin- the ovary and testis by Dr. Scully. In 1967 Dr. eate the various alterations of the glomerulus Gerald Nash and Dr. Blennerhassett, in collab- in a number of human diseases. Th ese eff orts oration with Dr. Henning Pontoppidan of the culminated in criteria that enabled electron Department of Anesthesiology, demonstrated microscopists to make fi rm diagnoses of many that many patients who died after mechanical human renal diseases in their earliest states. His ventilation had pulmonary lesions consistent investigations of heart muscle led to a defi nition with oxygen toxicity, and partly as a conse- of the conformance of cardiac muscle to classic quence it is now standard practice throughout length-tension curves as seen in skeletal muscle. the world to monitor closely the dose of oxygen Th is property of cardiac muscle is the basis of during mechanical ventilation. Other highlights one of the leading theories of heart failure, i.e., of our accomplishments in research include decrease in contractile strength of the muscle studies of Dr. Agnes Russfi eld on the correla- when overstretched and on the “descending tion between the cytology of the pituitary gland limb” of the length-tension curve. During his and hormone assays in neoplasia, assessment fi ve-year tenure before resigning to become of testicular biopsies in patients with infertil- a professor at Columbia University many of ity by Dr. Sniff en, and functional examination our residents and fellows were trained in this of the post-mortem heart to determine the new technic. Dr. James B. Caulfi eld took over

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the direction of this unit in 1961 and demon- pathway for sulfate ester synthesis from homo- strated renal glomerular changes in prediabetic cysteine requiring ascorbic acid and controlled patients and further noted that dermal elastic by pyridoxine. Th e search for a homocysteine tissue of prediabetics and diabetics is severely derivative with growth-stimulating proper- altered. Continuing work on cardiac diseases, ties culminated in the discovery and chemical Dr. Caulfi eld has defi ned the major cause of synthesis of an oxidize homocysteine derivative cardiogenic shock and the secondary myocar- mediating the action of pituitary growth hor- dial lesions induced by this syndrome. Recently, mone that he has called trophosine. Dr. Caulfi eld moved his laboratory to the Shri- Recognizing the increasing importance of ners building, where he is investigating ground immunologic thought and technology in the substance in wound healing. Dr. Ronald S. understanding and treatment of many dis- Weinstein and Dr. N. Scott McNutt, pathology eases, I established in 1959 an Immunopathol- research trainees using the equipment in the ogy Unit within our department, designed Mixter Neurosurgical Laboratory, applied high to serve as a focus of teaching, research, and resolution electron-microscopy technics to the diagnostic expertise in this fi eld. Under the study of normal and neoplastic cell membranes. able direction of Dr. Martin H. Flax this unit Th ey discovered a striking decrease in the num- formed close liaisons with clinicians in other ber of “nexus” cell junctions in carcinomas of units, such as the Renal Transplant Unit, with the cervix and found that this defi ciency arises improved patient care as a consequence. In as the epithelium undergoes malignant transfor- addition, Dr. Flax made fundamental con- mation. Since these junctions function as medi- tributions toward an understanding of the ators of intercellular communication in normal pathogenesis of autoimmune thyroiditis. His tissues, the decrease may partially explain the investigative activities created a tradition of abnormal behavior of tumors. Dr. Sanford I. intellectual excitement that was passed on to his Roth investigated the ultrastructure of normal successor, Dr. Harold Dvorak, when Dr. Flax and diseased parathyroid glands, complement- became professor and chairman of the Depart- ing my original light-microscope studies. ment of Pathology at Tufts University Medical He has demonstrated the form of the secre- School in 1970. From its inception this unit tory product, the secretory cycle in the chief has attracted several pathology residents annu- cells, and the independence of the control of ally for periods of research or clinical training parathyroid-hormone synthesis and secretion. in immunopathology, and more recently it has Th e chance fi nding by Dr. Kilmer S. McCully also attracted residents from other specialties. at autopsy of accelerated arteriosclerosis in two Dr. Dvorak’s research has been concerned with patients with homocystinuria resulting from the morphology and pathogenesis of cellular two diff erent enzymatic disorders led to the hypersensitivity. He has described a new form experimental production of arteriosclerosis in of lymphocyte-mediated immunologic response animals given homocysteine derivatives. Cell characterized by the presence of large numbers cultures from other patients with one of these of basophilic leukocytes, which apparently have types of homocystinuria were then found to a prominent role in such diverse entities as viral elaborate an abnormal highly sulfated matrix, infection, contact allergy, and tumor and graft accounting for the prominent accumulation rejection in both animals and patients. of matrix in the walls of arteries involved by Since 1958 we have been very fortunate in early arteriosclerosis. Investigation of these cell having a National Institutes of Health research cultures led to the discovery of a metabolic training grant to support four trainees per year.

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Its recipients obtain a basic training in ana- Charles Sanders. In his annual report for 1973, tomic pathology and in addition join one of with his characteristic humor he referred to him- the research units in the department or one of self as a “lame-duck Chief of Service”; but later the investigators in another hospital laboratory. in his same report he commented on a variety Th e purpose of this grant is to train academic of nonprofessional staff who had stepped down pathologists. It is of interest to compare this after many years of service: “Longevity seems to small group of trainees with the entire group be the rule in our department.” Indeed, it would of residents over this period; 80 percent of be for him: he continued in the department and the 30 research trainees are now in academic the hospital (including advising the General pathology, whereas 53 percent of the 70 regu- Director of the hospital) until he passed away in lar house staff are in academic pathology. We 1982, a remarkable period of over 50 years since are, of course, very proud of the fact that 26 of he had come to work with Tracy Mallory in 1931. our alumni of the last 25 years were appointed In 1982 another event occurred to honor Dr. to full professorial chairs, and that 15 of them Castleman’s contributions: the creation of the are or were chairman of departments at their Benjamin Castleman Professorship of Pathol- university. ogy at HMS. Just two weeks before he died, Dr. Castleman attended the ceremony making Dr. On October 29, 1971, a reception and dinner McCluskey, his successor, the fi rst incumbent were held in honor of Benjamin Castleman at the of the Castleman Professorship. Th e professor- Harvard Club. Over 200 alumni and department ship has subsequently been held by the two next members attended; attendance was increased by Chiefs of Pathology at MGH: Dr. Robert B. Col- members of the American Society of Clinical vin and Dr. David N. Louis. Pathologists who were in town for their annual meeting. As Dr. Castleman himself recalled, “It References was a heartwarming evening marked by many happy recollections of past events. It was indeed 1. Castleman B, Crockett D, Sutton S. Th e Massa- a memorable occasion of nostalgia and homage.” chusetts General Hospital, 1955–1980. Boston: Little, Brown, 1983. It turned out, however, that a successor was 2. Castleman B. Th e News. Massachusetts General somewhat slow in coming. Although Dr. Castle- Hospital 163, 1957. man had planned to step down as chief in late 3. Goodale F. Th e Absolute Truth and Other Uncer- 1972, it would not happen until 1974. In addi- tainties: A Remembrance. iUniverse, 2005. tion, between January and August 1972, he 4. Goldman H. In Memoriam. 2006; available served as Acting General Director of the hospital, from http://home.caregroup.org/BIDMCtoday/ between the directorships of John Knowles and 2006_09fall/memoriam.asp.

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