Chapter  Th e Clinical Laboratories (Chemistry and Hematology) Donna MacMillan and Kent B. Lewandrowski

he clinical laboratories (Clinical millions of tests per year with a menu of over TChemistry and Hematology) at the Mas- 1,500 diff erent tests (including those sent to out- sachusetts General Hospital (MGH) originated side reference laboratories), and with oversight with individual physicians interested in specifi c of all point-of-care testing as well. Th is chap- diseases for which biological and therapeutic ter traces the transition from the earliest docu- clues began to emerge from laboratory tests. mented times to the present day. Over time, custom tests developed for specifi c patients were repeated for patients with similar The Early Years symptoms; in this way laboratory tests progres- Clinical laboratories had a minimal role in sively moved from research to patient care. the early years of the hospital: “For the fi rst sev- Th e chemistry laboratory at MGH has a long enty-fi ve years of its life there was nothing really history. It began as a central facility but was worthy [of] the name of a laboratory. Impor- quickly accompanied by a group of independent tant work was carried out in a hole-and-corner specialty laboratories such as the Th yroid, Endo- way” (1). Even by 1872 the laboratory measured crine and Metabolism, Blood Gases, and Lipid only approximately 6 by 10 feet. Located on the Laboratories, which led to a decentralized and ground fl oor of the Bulfi nch Building, it was complex set of separate facilities. On the other described as a “small dark room used as a labo- hand, there is little mention of hematology as a ratory where specimens of urine were taken for laboratory science until the middle of the twenti- analysis” (2) (fi gure 20.1). Testing was performed eth century. For much of their history, therefore, by the house pupils (medical students) as part of the clinical laboratories were not recognized as their training. a unique specialty or operation: even as late as In 1851 Dr. John Bacon Jr. was appointed the the middle of the second half of the twentieth fi rst Chemist-Microscopist for the hospital. He century, the clinical laboratories were not iden- had graduated from Harvard Medical School tifi ed as a separate and distinct service. Th e last (HMS) in the class of 1840, and he was known two decades have witnessed progressive consoli- from his early years as a gentleman with a bent dations, resulting in centralization of laboratory for mechanics. While in Europe after graduation, services, although the recent emergence of point- he developed an interest in chemistry. Upon his of-care testing has moved some testing back to return, he quickly built a career around analytic the bedside. As a result, the present confi guration techniques. He was known for maintaining an is primarily that of a single large Core Labora- organized private laboratory with the highest tory in the department of Pathology, performing quality reagents, and his primary expertise was

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preparing specimens for crystal identifi cation. Dr. Consultants in Chemistry (chapter 1), Dr. James Bacon’s appointment to the MGH staff allowed C. White (1863–1872) and Dr. Edward S. Wood him to expand his activities and his reputation as (1872–1905), also had responsibilities at HMS. an authority on analytic chemistry (1). In making In 1893 the laboratories were described as “a this appointment, the Trustees were recognizing little den fi tted up under the front steps, and the early contributions of chemistry and micros- unfi t for human occupation; partly in the nurses’ copy to clinical practice and research: “Micros- rooms connected with the wards; partly at the copy and organic chemistry are now considered Medical School, a mile away; partly at the patho- legitimate specialties and a few among our most logical room in the department of out-patients” promising and intelligent medical men devote (1). In 1896 the new Clinico-Pathological Labo- themselves entirely to these interesting studies” ratory (chapter 3) was established in the Allen (1). Even after Dr. Bacon established a formal Street Building and included a chemistry labora- laboratory at the MGH, however, many physi- tory on the third fl oor. A separate house offi cer’s cians continued to do their own laboratory work laboratory for patient testing was located on the for their patients. second fl oor. Th e fi rst annual report from the In the mid-1860s the roles of Chemist and laboratory describes the facility as a model labo- Microscopist were divided, and Dr. Bacon’s title ratory for providing training opportunities. Dr. changed to Chemist. He served in this role until Franz Pfaff (chapter 3) was appointed Chemist in 1863, when he resigned because of illness and his 1897 and put in charge of the Chemistry Labora- growing workload at HMS as Professor of Chem- tory in 1898, but much of the laboratory work istry. He died in Boston in 1881, at the age of 64. was still performed by house offi cers. From 1863 to 1897 the role of Chemist changed In the early 1890s Drs. William Gannett and to that of Consultant in Chemistry. Th e next two Richard C. Cabot (house offi cer from 1893 to

Figure 20.1 Bulfi nch Building fl oor plan, 1872, with the laboratory (C) highlighted

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1894) started their work in the fi eld of hematol- patient and of using laboratory data to monitor a ogy (considered a medical specialty that included patient’s progress. In 1907 he wrote: examination of blood for malarial parasites) by When I see statements of blood counts which counting white cells in their patients’ blood spec- tell us, for example, that the patient had 5,633 imens. William Gannett (chapter 1) was born in leucocytes to the cubic millimeter, I cannot Boston in 1853, a descendent of John Winslow, help making two comments. First, that the one of the leaders of Plymouth Colony. He degree of accuracy to which the statement entered HMS in 1874 and was the fi rst student pretends is wholly useless; and second, that it to extend his studies to a fourth year for post- is only the pretense of accuracy after all. It is graduate work. During this year Gannett worked pseudo-science and not science. Now, if there as an assistant to physicians at the MGH. He is one thing which we who try to do scientifi c joined the MGH as a house pupil and received work should avoid more than another, it is, I his medical degree in 1879, offi cially joining the think this pseudo-scientifi c pretension—the MGH Medical Service after his graduation. He appearance of accuracy expressed in fi gures and fi rst spent a year in Vienna studying pathology, diagrams, when there is no such accuracy in and then returned to MGH in 1882 to start his fact. All blood counts should end with at least career as an Assistant in Pathology and Visiting two zeros, usually three. Physician. At HMS, Dr. Gannett was responsi- Th ere should be no diagnoses made merely ble for the laboratory work in pathological his- in the laboratory, and none merely at the bed- tology. Between 1882 and 1891 he also served as side, unless what are called “laboratory meth- Pathologist at Boston City Hospital and Carney ods” are carried out, as they may be carried out, Hospital. Dr. Gannett was an accomplished and at the bedside. (3) highly regarded diagnostician, and he continued seeing and consulting on patients in addition to In the early twentieth century, therefore, the his laboratory work. role of the laboratory in the clinical diagnosis was Richard C. Cabot (chapter 24) worked on still in question. Most physicians, like Dr. Cabot, blood pathology in collaboration with Dr. James emphasized the power of observation and overall Homer Wright. Dr. Wright’s research included medical knowledge; information from the labora- hematology (chapter 4), and the Wright stain is tory only provided confi rmation of the diagnosis. still used today. In 1894, Dr. Cabot was the fi rst recipient of the Dalton Scholarship and con- Typical Laboratory Workflow: tinued his work on the “minute examination of Early Twentieth Century blood.” During this time, he discovered red cell Laboratory specimens were usually collected by inclusions associated with certain anemias and interns in the fi rst six months of their training. disorders of erythropoiesis that are now termed Urinalysis and blood counts were performed in Cabot rings. His fi rst book, A Guide to the Clini- the ward laboratory under the supervision of the cal Examination of the Blood for Diagnostic Pur- laboratory leadership (“point-of-care testing,” in poses, was published in 1886. today’s lexicon). Orders for blood counts were Dr. Cabot’s career highlights the uncertainty of sent to the central laboratory. An intern was the role of laboratory testing in clinical diagnosis. assigned to collect the samples and perform the He rejected an off er to serve as the fi rst bacteri- counts. In the central laboratory, urgent (stat) ologist of the hospital in favor of a position in the tests were performed by interns on a rotating Outpatient Clinic. Nonetheless, he was an early basis. By today’s standards, the process for report- proponent of providing a specifi c diagnosis to the ing and archiving test results was cumbersome

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and labor-intensive. Results were handwritten on At the center of the debate was whether chem- a requisition form and forwarded to a clerk, who istry should be considered a pure science or an stamped them with a unique specimen number. applied branch of physiological chemistry. Also Each patient had an index card, and the clerk disputed was who should teach the subject: phy- typed the specimen number on the card so that sicians with knowledge of chemistry or chem- all the laboratory activity for the patient was ists with medical knowledge. As the entrance available in one location. Th en the clerk typed requirements for medical school were tightened the report in triplicate: one copy was sent to the and included undergraduate studies, students physician responsible for the patient, one copy came with a broader scientifi c background and was fi led by test name, and one copy was fi led an increasing variety of specialties they wished by diagnosis. Th is fi ling system made correlation to study. Th e discussion extended into the medi- studies of laboratory results to specifi c diagnoses cal school and the hospital, where the value of easier to complete. laboratory data was balanced against the value During this period funding for the laboratory of the bedside diagnostic skills of the physician. came from private donations. Usually, private Th e overall consensus was that laboratory infor- patients were charged an extra fee of up to $10 mation was an added benefi t for the physician. to cover the laboratory costs. Although initially As a result, laboratories in the wards continued used as a model for training, over time the lab- to operate, but interns were scheduled to work oratory became an important part of the diag- directly under a physician rather than perform- nostic process: its purpose was to provide rou- ing tests as time allowed. In 1910 the Board of tine laboratory assessments on urine and blood Trustees approved the addition of two laboratory for the patients in the wards. Th e test menu was assistants to the staff of the hospital. Th us, a new limited to urinalysis, hemoglobin, and white profession of medical technology was introduced blood cell counts. Urinalysis was considered an to the MGH: “We expect in the future to pay important test for “practical medical work.” Dr. laboratory workers enough to attract men of the Wright observed in the fi rst annual report (1898) fi rst ability, as modern medicine has become so that each admission had at least one urinalysis dependent for its success upon laboratory work” and often more than one. During this time, Dr. (4). Th e perception of the role of the laboratory Wright hired an assistant to perform basic duties had begun to change, and by 1918 Dr. Max Kahn, in the laboratory and to prepare special diets for Director of Laboratories at Beth Israel Hospital the patients. in New York City, wrote: “Treatment, in so far as it can do good, is nowadays directly propor- The Flexner Report, Otto Folin, tional to the amount of laboratory work. Given and the Emergence of Modern the diagnosis, it is a simple matter to treat—if Clinical Chemistry treatment is possible—any case. Th e rub is in Th e Flexner Report, released in 1910, was ascertaining the diagnosis” (5). intended to reform medical education. An addi- In 1917 the hospital created formal space for tional eff ect of the report was the development the Medical Laboratory on the fi rst fl oor of the of clinical chemistry as an integral yet indepen- Bulfi nch Building: six rooms with space for 12 dent medical discipline; hematology, however, workers. Th e laboratory was not viewed as an remained a part of Medicine, both as a clinical independent department, but rather was used discipline and as a science. One of the debates in by individuals who were interested in pursuing the reorganization of HMS and Harvard Univer- clinical investigation in their professional devel- sity was the placement and scope of chemistry. opment. In this model, tests were developed in

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conjunction with the services or clinics. Th e tests performed there were technically complex; rou- tine tests were performed on the second fl oor. After World War I work was done on blood gases (Dr. A. V. Bock, supervised by Professor L. J. Henderson), blood disorders (Dr. George Minot), thyroid disease (a collaboration with the Medicine and Surgical Services and the X-Ray Department), and analysis of blood and urine chemistries in diabetes and kidney disease (Dr. Reginald Fitz, son of Dr. Reginald Heber Fitz, chapter 2). Th e Medical Laboratory was also used for microbiology investigations. Along with the growth of the hospital’s inpa- tient service, its outpatient activities continued to increase: by 1917 there were over 200,000 visits in the Outpatient Department (6). Disease-specifi c clinics opened and included services for diabetes, blood disease, and thyroid and cardiac disorders. Hospital staff to support the outpatient service included laboratory technicians, and laboratory Figure 20.2 Otto Folin testing was included within each clinic. In this regard, laboratory testing was growing quickly analytic skills he had so carefully developed. He but was dispersed among many diff erent clinics fi lled the gap teaching at West Virginia Univer- and disciplines. sity and working in rudimentary basement labo- A product of this laboratory evolution was Dr. ratories. In 1900 his work was rewarded with an Otto Folin, who moved the science of chemis- appointment as a research chemist at the McLean try into the clinical chemistry laboratory (fi g- Hospital for the Insane, the psychiatric division ures 20.2 and 20.3, and see fi gure 3.5). He had of the MGH. Edward Cowles, the Superinten- come to the United States from Sweden in dent of McLean, had a long-term goal to build 1882 and received his doctorate in biochemistry a psychiatric research laboratory, and the labora- from the University of Chicago in 1898, which tory created for Dr. Folin was one of the fi rst in he described as “the wild and wooly west of sci- the United States. In the usual medical model of ence” (7). When he graduated there was little the day, patients were selected for inclusion in demand for college-educated biochemists, and so Folin’s studies on the basis of markers of men- he spent time studying in Germany, where the tal illness in urine. His early work was directed science of biochemistry had already been incor- to refi ning the analytical techniques that would porated into the study of physiology. While in quickly develop into the basic tools of a clinical Germany, Dr. Folin continued his interest in the chemistry laboratory. His research in colorimetry metabolism of nitrogen and had the opportunity during that time produced methods to quantify to be exposed to hospital patients while at the the amount of creatinine and creatine in urine Pathological Institute of the Charité Hospital in using alkaline picrates. Th e fi rst studies quickly Berlin. Returning to the United States, however, disproved the then-current belief that there was a he struggled to fi nd a career that leveraged the diff erence between the urine chemistry of normal

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individuals and of psychiatric patients. Dr. Folin department chair, Folin was also known as a expanded his research and concentrated on the gifted teacher and taught fi rst-year medical stu- chemistry of urine and its relationship to diet. dents. He continued his work training students In 1902 he began early studies on ammonia in in the laboratory. It was said that Dr. Folin was blood. Because there was little in the way of a quick to add humor to any setting, including commercial market for laboratory equipment or tricking his students into believing he performed chemicals at the time, he had to develop his own the long-obsolete urine taste test to detect sugar analytical devices and reagents before beginning in the diagnosis of diabetes mellitus! He was well his experiments. Dr. Folin subsequently devel- known for correcting students with the comment oped procedures to purify creatinine from urine “With all the mistakes you’ve already made, this and invented a preservative solution for collect- one is inconsequential” (7). Within a few years, ing 24-hour urines. he was promoted to full Professor. In 1907 Dr. Folin was recruited to Harvard Dr. Folin created a nationally recognized de- with an appointment as Assistant Professor and partment that began producing the next gen- head of the Department of Biochemistry at HMS. eration of biochemists. Among them was Hsien In this role he was the fi rst nonphysician on the Wu, who collaborated with Dr. Folin to develop faculty. Th is move was somewhat controversial, a relatively simple analysis for blood glucose that as the medical school and university struggled to would become the standard method for glucose respond to the failures in training described in testing well into the twentieth century. Wu was the Flexner Report. While serving as an eff ective born in 1893 in Foochow, China. He was sent to

Figure 20.3 Otto Folin in his laboratory at McLean Hospital

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college in the United States in 1911 and enrolled Joseph Aub observed: “By 1915 blood chemis- at the Massachusetts Institute of Technology to try was being done extensively in the very good study naval architecture, but he soon changed his chemical laboratory that Willey Denis ran, and I major to chemistry with a minor in biology. Wu’s remember her feeling of dissatisfaction with the graduate work was in organic chemistry, and in medical House Offi cers who, she said, did not 1917 he entered the doctoral program under Dr. have enough scientifi c interest to allow her to Folin. Th e two men quickly became friends and accumulate specimens. She said the dermatolo- collaborators. Th eir fi rst paper together, “A Sys- gists were the ones who really cooperated with tem of Blood Analysis,” was published in 1917 in her” (1). “Th roughout Denis’ sojourn at Harvard the Journal of Biological Chemistry (8). Dr. Wu and at the Massachusetts General Hospital, she left Harvard in 1920 to return to China, becom- was not forced into a woman’s role, except in ing the head of the Department of Biochemistry title; her collaboration with Folin was a matter of at Peking Union Medical College, the youngest choice and mutual esteem” (10). By 1917 she was department chair at the time. He expanded his managing her own research projects. With access work on methods for analyzing blood, including to patients, Folin and Denis could continue their deproteinization and labeled antigens. He also work studying patients with nephritis. A signifi - continued the teaching legacy of his mentor Otto cant by-product of their studies was establishing Folin and incorporated Western teaching and sci- normal values for blood creatinine and creatine. entifi c methods in China. In 1952 a heart attack Th ey also added turbidimetric methods for study- restricted Dr. Wu’s academic and research activi- ing protein to their established colorimetric tech- ties. He returned to Brookline, Massachusetts, niques. Th eir collaborative work resulted in 73 to start a second career by studying mathematics and using these skills to analyze data from radio- isotope patterns, authoring three more publica- tions before his death in 1959 (9). Another of Dr. Folin’s notable trainees was Dr. Willey Denis, a pioneer in her own right as one of the fi rst women to have a career in biochemistry and the fi rst woman to be appointed to the MGH staff (fi gure 20.4; chapter 3). She came to the fi eld following the same path as Dr. Folin, via the University of Chicago, where she completed her doctoral work in chemistry. In a six-month stay at Harvard in 1910, she completed early investiga- tions on the application of Folin’s urine analytic methods to blood analyses that resulted in three publications. In 1911 Dr. Denis returned to Har- vard as a research assistant, and in 1913 she moved to the MGH, though still within Dr. Folin’s pro- gram. She and Folin were given laboratory space in the Power House; he was appointed Chemist and she was made Assistant Chemist. By moving to the MGH, they had direct access to patients to further their biochemical investigations. Dr. Figure 20.4 Willey Denis

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publications between 1910 and 1920 (18). In 1920, administering Salvarsan (“606”) intravenously. after she left the MGH to take a faculty position Using both hospital and private patients, he at Tulane University in New Orleans (chapter developed an assay for urinary arsenic levels to 3), Dr. Denis further modifi ed the method for predict the amount of 606 circulating in the the analysis of protein in cerebrospinal fl uid. She blood. He demonstrated that four doses provided died in New Orleans in 1929. the greatest benefi t for the treatment of syphilis. Using the same technique, Dr. Boos developed Developments in Clinical methods to study alcohol levels in postmortem Chemistry and Hematology, cases of acute alcoholism. In 1910 James Homer – Wright reported a case of an elderly man with Under Dr. Folin’s leadership and as the discipline chronic heart disease who was admitted to the of clinical chemistry emerged, test menus began hospital; his urine laboratory results showed no to expand at the MGH. Additional tests by 1907 sugar and a specifi c gravity of 1.070. Th e medical included urinalysis (to distinguish at least seven staff approached Dr. Boos for additional labora- diff erent types of nephritis), analysis of urinary tory information. He identifi ed the problem as calculi, and “examinations of organs for the pres- magnesium poisoning. Having seen three other ence of exudates, transudate, etc.” Pharmaco- cases with similar characteristics, he began to logical investigations also interfaced with clinical study the absorption of magnesium. By 1910 chemistry. For example, the Chemistry Labora- he also perfected the biuret reaction for albu- tory test menu in the early 1900s included assays min and associated the presence of tryptic “fer- for both lead and arsenic: these tests were not ments” in the stool as a measure of pancreatic dis- performed to investigate heavy metal poisoning ease. One signifi cant test still performed by the but, rather, to monitor the therapeutic use of the “pups” (students) on the Medical Service was the metals and the patient’s progress. opsonic index. Th is test was used as a measure of Pharmacological laboratory tests were one of the activity of opsonins—chemicals thought to the interests of the chemist Dr. William Boos, be important in phagocytosis. Th e test was per- who worked collaboratively with his colleagues formed by comparing the number of organisms in the Medicine Service on cases with pharma- phagocytized in normal and infected patients. cology questions to produce new assays (chapter It was used for diagnosis, determining acuity, 3). Dr. Boos graduated from Harvard in 1894, and measuring the effi cacy of vaccines. It aided spent a year in graduate study in Germany, and the treatment of a variety of diseases, including returned to Boston and became an Instructor tuberculosis, erysipelas, puerperal fever, and scar- in Chemistry at Harvard beginning in 1896. He let fever. graduated from HMS in 1901 and was appointed By 1915 the laboratory service had expanded to the staff at MGH as a house physician. Like suffi ciently to begin reporting test volumes to many talented physicians, he was encouraged to the hospital. Dr. Willey Denis reported that the study abroad, and he spent four years as a research number of tests performed was 531, a signifi cant student at the University of Strasbourg Pharma- increase from the 102 reported in 1914. One of the cological Institute studying biological chemistry highest-volume tests was the colloidal gold test on and internal medicine. In 1906 he returned to spinal fl uid. Dr. Th omas Cunningham (a house Boston to launch his career, rejoining the MGH pupil on the Medical Service in 1918) recalled, staff as the Director of the Biochemical Lab and “We sent so many bloods for blood chemistries consulting in internal medicine. to the chemistry laboratory that they protested In 1910, Dr. Boos designed a tool for vigorously about it” (1). Th e chemistry test menu

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included nonprotein nitrogen, uric acid, glucose, Joseph Aub and Fuller Albright. Th e Diabetic urea (blood urea nitrogen), and creatinin (cre- Clinic opened in 1916 with the “hearty coopera- atinine). Calcium and phosphorus had just been tion” of the Chemistry Laboratory (1). In 1917 the introduced as routine tests. Hemoglobin assays Medical Laboratory was established; its primary were completed using the Tallqvist scale. With function was to support clinical investigations, the growth in the number and types of labora- including the practical use of blood gas assays. tory tests, “the early laboratory space was perhaps Th e laboratory was used by the clinic for moni- bizarre, and certainly disseminated” (1). In a 1916 toring and treatment of patients with unique or report, when the test volume had reached 1,060, interesting diseases. By the mid-1920s the resi- Dr. Denis described additions to the test menu: dent on each service was appointed a full-time measuring the daily output of urine sugar and lab worker. Th e clinics for epilepsy and rickets ammonia in diabetics and the reticulocyte count contributed to new blood chemistry tests, includ- for the diagnosis of pernicious anemia and bone ing blood pH and vitamin assays. Th e laboratory marrow status. Th e “pups” continued to perform operations increased to the point that the costs the complete blood counts. were recognized in a change in the hospital rates. In association with the rapid development In 1928 “there was another increase in admission of new techniques, new clinics and laboratories charges so that adults over 16 years were charged emerged in the hospital. For instance, in 1912 Dr. 75 cents for the fi rst visit and 50 cents for a sub- Boos had developed a method to measure urine sequent visit. . . . Th is increase was made to help pH in the evaluation of renal function; he made pay the expense of the laboratory work, which more than 2,500 observations in this study; he had grown a great deal” (1). then extended his studies to blood as physicians Laboratory-based hematology also emerged became interested in controlling pH in patients during this period as a distinct discipline at the with metabolic disease. With such techniques in hospital. Th e process of collecting blood speci- hand, Dr. James H. Means opened the Metabolic mens by venipuncture for laboratory testing was Laboratory in 1913. Dr. David Edsall, Chief of complicated and viewed by many as a surgical Medicine, quickly identifi ed Dr. Means as one of procedure. To facilitate the collection of speci- several talented interns with the potential to help mens, house pupils used a technique to collect launch a research program for MGH. Th e fi rst blood from the ear lobe into a small curved tube step was to gain expertise from leading authori- (1). Th is development enhanced the study of ties in the United States and Europe. When Dr. blood cells and facilitated the growth of hema- Means returned from his travels to MGH in 1913, tology as a discipline. For example, Dr. Wright Dr. Edsall created the laboratory for Dr. Means began early studies in the value of quality con- to pursue his interest in metabolism. Means’s trol in the development of his stain to study cell early work was pure research, but he quickly morphology. Drs. Roger Lee and Paul Dudley moved to more clinically oriented studies on White developed the coagulation time test in Dr. the thyroid and metabolism, including develop- Wright’s laboratory. ment of the basal metabolism test for diagnosing At this time, Dr. George Minot began his and monitoring patients with thyroid disease. In work on coagulation, hemophilia, and anemias 1925 before his move to become Dean at HMS, (fi gure 20.5). His laboratory was in the base- Dr. Edsall created Ward 4, the research ward that ment of the Bulfi nch Building, and all patients included laboratories to support the unit’s activi- with blood disorders were referred to him for ties. Dr. Means was appointed Chief of Medical his detailed review of their blood smears. He Services, and his research team included Drs. had been born in Boston in 1885 and had a long

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lineage in Boston medicine; his grandmother was the daughter of James Jackson, cofounder of the MGH. He studied at Harvard and received his medical degree in 1912. While in medical school, Minot worked in an outpatient clinic staff ed by HMS faculty and began his diagnostic career by distinguishing pernicious anemia from con- genital hemolytic anemia. His HMS instructors included Drs. Otto Folin and Walter B. Cannon. When Minot enrolled in a hematology elective taught by Dr. James Homer Wright, his interest and career in hematology was sealed. Dr. Minot joined the staff at MGH as a house pupil for the Medicine Service in 1912. He continued to explore the link between nutrition and anemia and became interested in the study of blood fi lms in these patients. When he completed his year as house pupil, Minot joined the ranks of junior faculty and then went to Johns Hopkins to con- tinue his work and develop his skills. During his Figure 20.5 George Minot tenure at Hopkins, his basic research contributed to the preparation of heparin from livers. Prize in Physiology or Medicine). In 1923, Dr. In 1915 Minot returned to Boston as an Assis- Minot left MGH and was appointed the Chief tant in Medicine at MGH and Assistant in of the Medical Service at the Huntington Hospi- Chemistry at HMS. Dr. Minot, along with other tal. Despite an active clinical and research career, notable junior faculty such as Drs. James Means he managed to mentor students, often by writing and Paul Dudley White, operated in the medical notes on recent publications that related to their model of using science to understand and treat work. By the time he reached his mid-fi fties, the disease. Minot found space to set up a microscope complications from his diabetes started to restrict in the “inner sanctum of the hospital’s irascible his activities, and in 1947 he suff ered a debilitat- pathologist, Dr. Wright” (11). During World War ing stroke, which kept him in a wheelchair for I he consulted on cases of anemia in ammunition the rest of his life. After the stroke, he resigned factory workers, and after the war he received a from his formal positions but followed his staff joint appointment at the Huntington Hospital, and their research on an informal basis until where he had an opportunity to continue his his death in 1950. His seminal work played an study of blood disorders. In 1921 Minot was diag- important part in establishing the disciplines of nosed with diabetes. At the time the only treat- clinical and laboratory hematology. ment consisted of severe diet restrictions. When insulin was discovered in 1922, Dr. Elliott Joslin, Fuller Albright and the Emergence Minot’s physician, was able to obtain it in suf- of Laboratory Endocrinology fi cient quantity to allow Minot to continue his work, which culminated in the 1926 publication Fuller Albright was born in 1899 and graduated of the eff ect of the use of liver to treat pernicious from Harvard College in 1919 and HMS in 1924 anemia (work that resulted in the 1934 Nobel (fi gure 20.6). After graduation, Dr. Albright,

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includes early-onset puberty in girls, bone cysts, and changes in skin pigmentation. Dr. Albright’s work in the research lab produced analyses that developed into some of the basic endocrine test menu of today: gonadotropins in urine, sex hor- mones, and parathyroid hormones. In the mid- 1930s Fuller Albright began to develop the early signs of Parkinson’s disease. Despite progression of the disease and with the devoted assistance of his wife, Albright continued his work on Cush- ing syndrome, the use of estrogen to control ovu- lation, and the harmful eff ects of steroids. He is remembered for his many trips to the Pathol- ogy department to review histology and for his unlimited enthusiasm for his work and for life in general. Dr. Alexander Leaf, Chief of Medicine 1966–1981, recalled: “One day he was joined by a young aggressive foreign visitor in attendance at one of his clinics. In the course of the discussion regarding one of the patients seen on that occa- sion, the visitor reprimanded Dr. Albright for not having read the visitor’s writings on the subject. Figure 20.6 Fuller Albright Whereupon Dr. Albright humbly apologized for his negligence but added, ‘I hardly have time to intrigued by recent scientifi c discoveries in bio- read my own’ ” (12). After unsuccessful experi- chemistry and physiology, focused his career on mental surgery in 1956, Fuller Albright remained combining direct patient care with investigation in a coma until his death in 1969. of the endocrine system. His fi rst interest was the metabolism of calcium. He spent time at Johns The s, s, and s Hopkins with his lifelong friend and collaborator, In the 1930s the laboratory operations were dis- John E. Howard; their collaboration was so close tributed between the second fl oor of the Phillips and spontaneous that they frequently could not House (private patients), with one unsupervised attribute ideas to one or the other. After return- technician, and the second fl oor of the Baker ing to MGH, he used the information from his Building, which opened in 1930 with three tech- clinical work to determine his research into dis- nicians and a supervising physician. Th e labo- eases that had not been previously defi ned. Much ratory technicians covered the two operations of his patient work was performed in the Metab- as the level of activity warranted. Th e Phillips olism Unit (Ward 4), where he worked closely laboratory consolidated with the Baker Labora- with Dr. Means (12, 13). His investigations led to tory in 1933 to conserve space and resources. Th e one of the fi rst descriptions of hyperparathyroid- test menu for these laboratories was limited to ism, and the work in his Stone Clinic provided hematology. Th is was due in part to the instabil- some of the earliest descriptions and treatments ity of the hematology specimens. Without eff ec- for kidney stones. Perhaps his most notable work tive anticoagulant additives, the cell counts and bears his name: Albright’s syndrome—which smears had to be performed on fresh specimens.

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Th e laboratory supported the Consultation Pathology, reported a signifi cant growth in the (Diagnostic) Clinic and helped produce blood Chemistry Laboratory: its annual volume had grouping sera for the Blood Bank. In 1933 the reached 18,886 tests. He stated, “In spite of this laboratory was opened on weekends for the fi rst marked growth, there has, unfortunately been no time, on Saturday afternoons and Sunday morn- increase in the amount of space for the Chemis- ings. By the end of the decade there were small try Laboratory until last year when I succeeded laboratories in the Emergency Department, the in getting a very small additional corner of space” Outpatient Department, the White Building (1). Th e Chemistry Laboratory had expanded (for surgical patients), and the Vincent Burnham that year to accommodate new equipment (calo- Building for the obstetrical patients. Despite the rimeter, microscope, and a balance) necessary for addition of laboratory technicians, the house the 30 percent growth expected with the opening pupils were still expected to perform laboratory of the Baker and White buildings. tests. Th e growth in laboratory testing responsi- In the 1940s there was continued innovation in bilities led to the decision to increase the number technology and tests in the laboratories. Despite of house pupils to 67, which resulted in a ratio to the growth, the Baker Laboratory had a reduc- patients of 1 to 10 (down from 1 to 15 in 1900). tion in personnel. It continued to operate with In the same year the laboratory in the Operat- a menu of total protein, hematocrit, and hemo- ing Room/Anesthesia Department raised $1,500 globin in cooperation with the Medical staff . Th e in private donations to help defray expenses. In annual report of 1944 off ers a proposal for new their individual specialty labs, signifi cant work laboratory space for all the routine laboratories, was done on the development of new labora- citing the advantage of collaboration and consul- tory assays for parathyroid hormone (Dr. Joseph tation. In the late 1940s Dr. Hunter perfected the Aub), sex hormones (Dr. Fuller Albright), thyroid use of spectrophotometric methods for quanti- hormones (Dr. James Means), and anemias (Dr. tative assays and eliminated interference caused George Minot) (fi gures 20.5, 20.6, and 20.7). by turbidity. Despite the interest in consolida- By the mid-1930s there were three types of tion, two new laboratories opened: the Enzyme laboratory in the hospital: the clinical laboratories Laboratory of Dr. Fritz Lipmann (who won the for patient care, research laboratories, and disease- Nobel Prize in 1953 for his work on coenzyme A) or organ-oriented laboratories that integrated on Bulfi nch 3 and the Anesthesia Laboratory on research and clinical care. In 1937 the General White 4. Executive Council approved a report recommend- With the continued development of new tech- ing a reorganization of the “routine laboratories,” nologies in the 1950s, the scope of the clinical which resulted in the consolidation of the clini- laboratories grew. Th e model did not change, cal laboratories into Pathology administration. however: tests were performed in specialized lab- Dr. Francis Hunter, responsible for the Baker and oratories defi ned by specifi c clinical disciplines. Phillips laboratories, was appointed the Clinical Resident training included chemistry and hema- Pathologist. Hunter graduated from Harvard in tology (through the Medicine Service) and was 1919 and HMS in 1924. From there, he joined provided not only for Medicine residents, but the MGH staff as well as the Massachusetts Eye also for physicians interested in a career in clini- and Ear Infi rmary as a consultant physician and cal pathology. pathologist. He was viewed as an expert in X-ray Dr. Hunter died in 1954 at the age of 57, hav- safety, and during World War II he helped main- ing directed the large clinical laboratories at tain the war records of MGH personnel. MGH for 17 years. At this time the Hematol- For 1938 Dr. Tracy Mallory, the Chief of ogy Laboratories were temporarily assigned to

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Dr. Charles DuToit, the Director of Chemistry. the Technicon AutoAnalyzer, was implemented. Hospital leadership decided that hematology was Each of these early platforms performed one developing into a unique specialty and appointed electrolyte assay using automated sampling and Dr. William Beck as Director of the Baker Labo- continuous fl ow. Th e hospital also opened a one- ratory and the new Hematology Unit. Dr. Beck year laboratory training program for 10 students was recruited from New York University to the from Simmons College that included rotations MGH in 1957; his interest was hematology, with in Pathology, Medicine, Bacteriology, and the a focus in biochemical research. At MGH he Blood Bank. continued his work on vitamin B12, DNA syn- thesis, and pernicious anemia. When the Har- The s and s, and the vard–MIT Health Sciences and Technology pro- Beginning of Computerization gram started, Dr. Beck was named the Director and Automation of the Hematology course. At the same time, Dr. Th e 1960s saw rapid growth in the laboratories. Beck directed the Hematology Program at HMS. Th e test volume grew from 259,553 tests per year He continued his work and teaching even after in 1960 to 745,358 in 1970 (the fi rst year that being diagnosed with pancreatic cancer, until his cumulative statistics were produced by the com- death in 2007 (14). puter). Th is was attributed to increased utiliza- Under Dr. Beck’s direction the Hematology tion in the Outpatient Department, since few Laboratories became the service laboratory and beds were added to the hospital during this time. were known as the Clinical Laboratories. Most In the early 1960s MGH clinical services con- of the laboratory work in Hematology was still vinced the hospital leadership to eliminate labo- performed by the medical students and interns ratory work from the house staff ’s responsibili- as part of their patient care responsibilities. Th e ties and transfer it to dedicated laboratory staff . experience of doing cell counts and urinalysis was Th e Surgical Service started the transition, and viewed as a valuable part of their training as phy- the Medicine Service followed. Th is signifi cant sicians. Dr. Beck recalled, “Th e weary house offi - change did not aff ect the specialty laboratories cer would return to a dismal, crowded laboratory still active in the services. Dr. Myron Laver joined after his other work was fi nished” (15). the Surgical Service during this time and opened Dr. DuToit continued as the Director of the the Blood Gas Laboratory to support the grow- Chemistry Laboratory on the fourth fl oor of the ing interest in laboratory assessment of respira- Domestic Building, and G. Margaret Rourke was tory status during and after surgery. Dr. Laver the lead technologist of a staff of 12 technologists. designed and built many of the early blood gas Methods included protein electrophoresis (one analyzers. As the anesthesiologists noted in a his- of the earliest uses of electrophoresis in the coun- tory of their department, the “perfected accuracy try) and fl ame photometry. Th ough the model of and speed in providing serial blood gas analyses disease-based research combined with a clinical . . . enabled physicians to follow rapidly changing laboratory for esoteric tests continued (for exam- clinical situations” (15). In its fi rst year the Blood ple, in the 1950s the Immunology and Allergy Gas Laboratory performed 3,000 tests. Th e initial Unit opened, along with the requisite laboratory plan was to have the Chemistry Laboratory staff dedicated to developing and performing tests the Blood Gas Laboratory, but the leadership of for patients with immunological disorders), the the Chemistry Laboratory was not interested in Chemistry Laboratory provided support to all developing that part of the specialty (J. Flood, clinical services, performing the basic routine personal communication, 2010). Th e Th yroid tests. In 1955 the fi rst automated technology, Laboratory opened in the Bulfi nch basement and

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performed thyroid-stimulating hormone (TSH) it operated around the clock throughout the year. and thyroxine binding pre-albumin testing at no Routine samples were accepted Monday through charge to the patient. Dr. Lot Page in the Hyper- Saturday from 9:00 a.m. to 5:30 p.m. In 1965 the tension Clinic developed the renin assay. Th e Chemistry Laboratory had a menu of 130 tests, Cardiac Unit (and laboratory) opened in 1965 most of which were off ered 24 hours a day; there under the direction of Dr. Paul Dudley White. were fi ve AutoAnalyzers and an enzyme analyzer In that laboratory Dr. Edgar Haber developed an in the laboratory, most running at 50 percent assay for digoxin. capacity. In 1961 Dr. Sidney Rieder was appointed the In 1965 the MGH chemistry laboratories per- Director of Chemistry. His appointment was in formed over 1,000,000 procedures, an increase Medicine rather than Pathology. Dr. Rieder came of 70 percent in fi ve years. Physicians were to the MGH from the Department of Biochemis- responsible for completing the laboratory req- try at Yale University School of Medicine. While uisitions; specimens were collected according to there, he had worked with Dr. Irwin A. Rose, the requirements of the laboratory performing who went on to receive the 2004 Nobel Prize in the procedure and hand-delivered to the labora- Chemistry (16). In his autobiographical note for tory by a messenger service. Th e samples were the Nobel Prize, Dr. Rose recognized Dr. Rieder recorded in a logbook, and the tests scheduled by as one of many who had helped him solve prob- the laboratory technician. Up to 32 color-coded lems in his early years of biochemical research test worksheets and up to 90 total pages were (17). Th ere were two head technologists to man- transcribed by the laboratory technicians every age the growing volume: Olive Holmes and Mary day. Test results were manually transcribed from Zervas. With the volume expanding by 20 per- each worksheet onto the original multipart req- cent each year, the Chemistry Laboratory imple- uisition. Th e original requisition was sorted and mented a four-channel AutoAnalyzer and added returned to the patient unit, a second copy was a third head technologist. Th ere were about 40 fi led for billing, and a third copy was saved in the technologists in the Chemistry Laboratory, and laboratory for fi ve months. Requisitions were sent back to units via dispatch at 3:30 p.m. and 6:30 p.m. Th e laboratory scheduled its testing activity on the basis of the number of specimens deliv- ered to the laboratory on any given day. Although tests were performed continuously throughout the day, the results were not sent back to the unit until after 5:00 p.m. Although the laboratory was open 24 hours a day, only emergency specimens were accepted after 5:30 p.m. Th is schedule was frequently abused; Dr. Rieder reported, “On Sat- urday 20 of the slips coming to the Chemistry Laboratory bore the red sticker indicating that they were emergencies.” He cited an example of one of the house offi cers who got up at 5:30 and aroused his patients, secured blood, marked them all with red slips, and got them down to the labo- Figure 20.7 Paul Dudley White (left) and ratory. When the house offi cer was asked about James Howard Means the necessity of this, it became clear that many of

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these were not emergencies. “Th is example only systems for processing patient information. Th is points out one fact of what is a very large prob- was a joint project with an outside consulting lem,” Dr. Rieder observed (18). fi rm and was funded through the National Insti- In 1966 the Gray Building opened, and new tutes of Health. Dr. Barnett was a trained cardi- space on the second fl oor housed the Hematol- ologist with a particular interest in the applica- ogy, Special Hematology, and Coagulation Labo- tions of computers to medicine. Using data that ratories. In the same year Medicine completed the included patient medical and personal informa- transition of laboratory tests being performed by tion to develop computer systems was controver- technicians rather than house staff . Th is move was sial. He started by identifying areas of the clini- accelerated with the introduction of the Coulter S cal operation in which clear information fl ow automated cell counters, which required training was a priority to the physicians providing care, to operate. Th e service levels of the Hematology and the laboratories were identifi ed as a prime Laboratories varied greatly, and diff erences in the opportunity. One of his earliest eff orts resulted menus on the automated cell counters introduced in COSTAR (Computer Stored Ambulatory confusion. Th is was further complicated by the Record), developed in the MGH Laboratory for decision to eliminate the order “CBC” (complete Computer Science; it was one of the fi rst labo- blood count), because each laboratory performed ratory systems in the country. Th ere were many a diff erent panel. (Th e Baker Laboratory CBC benefi ts; for example, following the introduction included a white blood count, hemoglobin, and of computer systems, it was reported that “in cell diff erential, whereas the CBC of some of the some areas of the hospital, the turnaround time other laboratories included a hematocrit instead from drawing of blood samples to the report is of hemoglobin.) Consequently, it was diffi cult less than an hour” (15). Th e information system for physicians to follow the course of a patient’s included several automated quality assurance care. Th e ease of ordering a CBC test was also thresholds, including delta-checks and abnormal identifi ed as the cause for the volume increase in fl ags that prompted the technician to verify the daily CBC orders on long-term patients. Order- result before release. Chemistry and Microbiol- ing the individual analytes as opposed to a panel ogy were the early adapters, followed by Hema- was presumed to add clarity—one of the earliest tology, Blood Bank, Pathology, the acute care eff orts at managing laboratory test utilization in laboratories, and various specialty laboratories. the hospital. Th e Special Hematology Laboratory By 1970 the MGH laboratory information sys- performed vitamin B12, folic acid, and leukocyte tem was one of the largest in the country and was alkaline phosphatase. adapted by other institutions. Th e system had In 1967 the growth in the volume of avail- several functions, including worksheets, patient able laboratory data and the emergence of new inquiries, results reporting, billing, and statistics. laboratory regulations required improved ways to Th e fi rst computer application was used for inter- make this information available to providers. Dr. nal laboratory operations only, and the second Octo Barnett was recruited in 1962 by Dr. Rob- phase expanded to include manual result entry ert Ebert, the Chief of Medicine, who believed (eliminating many handwritten test results) and “the enormous information transmittal problems cumulative reports. Th e last phase included accu- involved in the practice of medicine in a large mulation and manipulation of data and interfac- hospital might be simplifi ed, and the availabil- ing of laboratory instruments to the laboratory ity of data upon which medical practice is based information system. Th e scale of the task soon might be improved by the computers” (15). Dr. exceeded the technical capabilities of the avail- Barnett was recruited to develop computerized able computer programming languages. Dr.

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Barnett and his team then developed MUMPS now included the thromboplastin generation test, (MGH Utility Multi-Programming System) to thrombin time, fi brinolysis, fi brin solubility in accommodate multiple users. Dr. Barnett wrote: urea, euglobinlysis time, and factor assays. In 1968 the Chemistry Laboratory moved to Th e major fi nding of this evaluation is that the fourth fl oor of the Gray Building with a staff the principle impact of automation in the of 60 employees. Th ere was also a separate Blood chemistry laboratory has been to increase its Gas Laboratory on White 4 that off ered rapid capacity and make it unnecessary either to hire turnaround time and callback of test results to more manpower or to reorganize the system in the patient location. Th e Blood Gas Laboratory order to handle a rapidly increasing load. Two also introduced an interesting billing structure: indices of success of this system are important, the patient was charged $10 per sample, with a although both are subjective. Th e fi rst is the maximum of $25 per day. dependency of the hospital operation on the By 1969 automation was expanding in both function of the system (the chemistry labora- Chemistry and Hematology. Chemistry began tory director is convinced that his laboratory releasing the fi rst automated laboratory reports: would have been in absolute crisis by now were consolidated reports printed from the computer it not for the computer system) and the will- to replace handwritten results on a requisition. ingness of the hospital administration to both Th ere were frequent communications to the units purchase a computer system and support the emphasizing the need for legible requisitions continuing operational costs out of patient care and full information. In an attempt to improve charges. (19) quality of care, laboratory leadership considered Even with the introduction of computers, the rejecting specimens received without a medical majority of the laboratory work was performed on record number. Atomic absorption and auto- paper. Th e paper requisitions were color-coded to mated enzyme assays were added to the Chem- facilitate deliveries to the correct specialty labo- istry menu. Th e Hematology Laboratory was ratory. Th e Clinical Laboratories (Hematology) processing 500 specimens a day, and a Coulter B had fi ve unique locations: Baker, Bulfi nch, Burn- instrument was acquired to automate the platelet ham, Outpatient Department, and White 6. Th e assay. All the laboratories performing hematology proliferation of test requisitions can be illustrated tests moved to space on Gray 2 and merged with by a consideration of the Clinical Laboratories the Coagulation Laboratory. Virtually all the sat- to develop a special requisition for prothrombin ellite hematology laboratories were closed, with time because the secretaries were spending too the exception of a laboratory in the Emergency much time on the 200 samples received each day. Department. Dr. Rieder was a strong proponent of computer Th e tradition of setting up autonomous special- solutions and felt that this would all be solved by ized laboratory services continued in the 1970s. computerization. A new admitting area opened in 1971, supported Th e Coagulation Laboratory was also grow- by a dedicated laboratory. In Endocrinology, Dr. ing, having taken over the prothrombin time test Farahe Maloof introduced the most sensitive from the Chemistry Laboratory and the hista- TSH assay available at the time. Th e Endocrine mine test from a research laboratory. Th e labora- Unit also began performing parathyroid hormone tory encouraged use of the partial thromboplastin tests using the relatively recent immunoassay time (PTT) as a screening test over clotting time. techniques. A new Intensive Care Unit opened on Coagulation testing moved from the Baker Labo- Gray 3A, supported by a new Blood Gas Labora- ratory to new space created on Gray 2. Th e menu tory. By the middle of the decade the Blood Gas

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Laboratories performed over 100,000 tests per Pathology. Over the next two decades this pro- year. During the 1970s laboratory medicine at the cess transformed the clinical laboratories from a national level was progressively moving toward group of autonomous specialized testing facilities more formal systems for quality control and qual- into a coordinated division of Pathology respon- ity assurance. Th e MGH Chemistry Laboratory sible for providing comprehensive laboratory ser- implemented a semi-automated quality control vices. Th e initiating event was the decision by the statistical package in the mid-1970s. hospital in 1988 to recruit a Director of Clinical In 1975 Dr. Leonard Ellman was appointed Laboratories. Following a national search, Dr. director of the Hematology Laboratories (also Michael Laposata was recruited from the Univer- known as the Clinical Laboratories at that time). sity of Pennsylvania to become the fi rst Direc- Dr. Ellman had been Chief of the Hematology tor of Clinical Laboratories at the MGH (fi gure Unit in Medicine since 1971. He continued the 20.8). teaching activities of the unit and expanded the Dr. Laposata received his M.D. and Ph.D. clinical Hematology Service. Dr. Ellman contin- from Johns Hopkins University School of Medi- ued as Director of the Hematology Laboratories cine and completed a postdoctoral research fel- following the 1977 merger to form the Hematol- lowship and residency in Laboratory Medicine ogy-Oncology Unit in Medicine. (Clinical Pathology) at Washington University Th e laboratory associated with the Immunol- School of Medicine in St. Louis. He took his fi rst ogy and Allergy Unit, dedicated to developing faculty position at the University of Pennsylva- and performing tests for patients with immuno- nia School in 1985, where he was an Assistant logical disorders, also grew. Under the leadership of Dr. Francis Cabot Lowell in the 1960s and early 1970s and Dr. Kurt Bloch following 1976, many new assays of the immune system were developed. Dr. Bloch was recruited to be the Chief of the new Immunology and Allergy Unit, and he com- bined his work in rheumatology on the Medical Service with the developing fi eld of immunology. As Dr. Alexander Leaf, the Chief of Medicine, observed: “With the strengths of the Pathology Department in immunology, close relationships have developed with that department, although occasional jurisdictional disputes have surfaced regarding teaching roles and territory with respect to certain clinical immunologic tests” (15). The Modern Clinical Laboratories In the 1980s economic issues prompted a consid- eration of effi ciency and consolidation of labora- tory services. One of the earliest changes resulted in the closure of the Gray 3A laboratory. But in the late 1980s there began a more progressive trend of laboratory consolidation and centralization of laboratory management under the department of Figure 20.8 Michael Laposata

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Professor and Director of the hospital’s Coagu- Table 1. Individual Clinical Laboratories and Their lation Laboratory. In 1989 he became Director Departmental Affi liations in 1988 of Clinical Laboratories at the MGH and was Laboratory Department Affi liation appointed to the faculty at HMS, where, as a of Director dynamic teacher, he eventually became a full Pro- Clinical Chemistry Hospital Administration fessor of Pathology. Laposata’s clinical focus was Acute Care Laboratory Cardiac Anesthesia in blood coagulation, and his research focused on Pediatric Microchemistry Pediatrics fatty acids and their metabolites. Reproductive Endocrine Endocrinology (Medicine) At the time of Dr. Laposata’s recruitment, Laboratory the clinical laboratories were scattered across Thyroid Endocrine Endocrinology (Medicine) the MGH campus, and many laboratories were Laboratory directed by physicians from medical specialties Gastrointestinal Laboratory Gastroenterology outside Pathology (see table 1); little attention was (Medicine) given to coordinating clinical laboratory services Diabetes Laboratory Endocrinology (Medicine) within the hospital. Several laboratories were Clinical Immunology Allergy/Immunology (Medicine) not computerized and still relied on handwrit- Neurochemistry Laboratory Pediatrics ten paper records. In laboratories that did have Hematology Hospital Administration/ computer systems, there was a mixture of home- Hematology-Oncology grown and customized commercial systems that Microbiology Hospital Administration/ could not be networked into a single labora- Infectious Diseases tory information system. Soon after his arrival, Blood Transfusion Services Surgery Dr. Laposata began working with colleagues to Phlebotomy/Transport Hospital Administration craft a strategic vision for the clinical laborato- ries, emphasizing the emerging role of laboratory medicine as a distinct specialty within Pathology. has an MBA in Health Management from Boston Highlights of this vision included: University. Her areas of interest include regulatory compliance, process improvement, and quality 1. Consolidation of the management of the clin- and safety. Beginning in 2004, her role expanded ical laboratories under Pathology to cover Anatomic Pathology as well, as Director 2. Development of a formalized Clinical Pathol- of Operations for the Pathology department. ogy resident training program Over the ensuing decade, nearly all clini- cal laboratories were sequentially consolidated, 3. Development of formalized laboratory-based which ultimately resulted in the confi guration consultative services to support MGH phy- that exists today (table 2). Th e fi rst consolida- sicians in the selection and interpretation of tion occurred in 1990 and involved the Pediatric laboratory tests Microchemistry Laboratory and the Acute Care 4. Implementation of modern instrumentation Laboratory; this consolidation was a logical move and laboratory information systems. because both laboratories provided whole blood testing for blood gases and electrolytes and other Dr. Laposata created an overall coordinat- tests relevant to acute care settings (adult inten- ing administrative position within the Clinical sive care units, cardiac surgery, and the pediatric Pathology Division and hired Donna MacMillan intensive care unit). In 1997 the largest consoli- in 1994 to fi ll the role. MacMillan’s undergradu- dation occurred, combining Clinical Chemis- ate work was as a medical technologist, and she try, Th yroid Endocrine, the new Acute Care

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Laboratory, Reproductive Endocrine, and the Table 2: Confi guration of the MGH Pathology Lipid Laboratory, which led to the formation of a Clinical Laboratories (ca. 2011) full service chemistry-immunochemistry labora- Laboratory Comment tory on Gray 5. In subsequent years other labora- Core Laboratory The Core Laboratory on Gray 5 tories consolidated into this operation, including represents the fi nal organization the Gastrointestinal Laboratory, the Neurochem- of a number of individual labora- istry Laboratory, and the Clinical Immunol- tories including clinical chemistry, ogy Laboratory. Another major transformative hematology, thyroid endocrine, reproductive endocrine, lipid event occurred in 1999 when a single commer- laboratory, gastrointestinal labo- cial laboratory information system (Sunquest) ratory, pediatric microchemistry, was implemented by Dr. James Flood. Dr. Flood acute care, clinical immunology, had received his B.A. and his Ph.D. in Analytical and neurochemistry Chemistry from Lehigh University. After clinical Microbiology Includes bacteriology, virology, chemistry training with Drs. George Bowers and molecular microbiology, parasi- Robert McComb at Hartford Hospital, he joined tology, serology, mycobacteriol- ogy, and mycology MGH as Assistant Director of the Chemistry Diabetes Laboratory Performs specialized testing Laboratory in 1980. In 1984 he became Direc- related to diabetes mellitus tor of the Chemistry Laboratory. His research Blood Transfusion Includes the blood donor service interests include analytical toxicology, automa- Services and blood transfusion services tion, and computer applications in the clinical Laboratory Support Includes phlebotomy, some trans- laboratory. Services port services, and a centralized Th e new information system replaced fi ve phone service (4-LABS) obsolete legacy systems that could not be net- Point-of-Care Testing Provides oversight of bedside worked: for the fi rst time all of the major clinical testing performed by physicians laboratories were united on a single laboratory and nurses across MGH campus information system. Finally, in perhaps the larg- est consolidation to date, the Clinical Chemistry Laboratory was combined with the Hematology the MGH, and joined the faculty in 1991, serv- Laboratory, which moved from Gray 2 to Gray 5 ing in various leadership capacities in the clinical in 2006. Th is event marked the physical creation laboratories and being appointed Associate Chief of the current Core Laboratory on Gray 5; for of Pathology and Director of Clinical Services the fi rst time, all the major testing laboratories, (combining anatomic and clinical pathology) including Chemistry, Hematology, and Micro- in 2006. His research interests include studies biology, were located in one contiguous space on critical care/point-of-care testing and pan- on Gray-Jackson 5. It also brought to a close the creatic pathology. Along with Dr. James Flood, decadelong process of creating a single consoli- the Director of Clinical Chemistry, he oversaw dated laboratory supported by a modern labora- most of the many consolidations that ultimately tory information system. resulted in the formation of the Core Laboratory. Dr. Kent B. Lewandrowski was the fi rst Core When Dr. Lewandrowski assumed oversight of Laboratory Director and also served as the Asso- all departmental clinical operations in 2007, Dr. ciate Chief of Pathology. Dr. Lewandrowski Anand Dighe became the Director of the Core received his M.D. from the University of Mas- Laboratory. Dr. Dighe had received his under- sachusetts Medical School, completed his resi- graduate degree from the Massachusetts Institute dency in Anatomic and Clinical Pathology at of Technology and his M.D. and Ph.D. degrees

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from Washington University in St. Louis. He was combined with the Division of Anatomic then spent six years in the information technol- Pathology into a single administrative Clinical ogy industry. After completing clinical pathol- Services Division led by Kent Lewandrowski. ogy residency training at the MGH, he joined Th e growth of the Core Lab and its subspe- the faculty and is currently Director of the Core cialties led to an expansion of the faculty as well, Laboratory and Associate Director of Pathology as the Core Lab faculty grew to six members in Informatics. His research interests include the addition to Drs. Dighe and Flood (in alphabeti- application of information technology to the cal order): Drs. John Higgins, Elizabeth Lee- laboratory testing process, from test ordering to Lewandrowski, Mandakolathur Murali, Patrick test interpretation. Sluss, Aliyah Sohani, and Elizabeth Van Cott Th e next major advance in the Core Labora- (fi gure 20.9). Dr. Higgins graduated from HMS tory occurred in 2010 with the implementation in 2004 and came to the MGH in 2009 as an of a fully automated chemistry-immunochemis- Assistant Professor of Systems Biology and Assis- try system. Th is system uses a track method and tant Pathologist. He serves as a Clinical Consul- robotics to move specimen tubes through the tant to the Hematology Lab, and his academic laboratory. Th e automated “line” includes instru- work is in the mathematical modeling of human mentation to perform specimen processing, disease processes and in population dynamics including centrifugation, decapping of tubes, of red and white blood cells and blood fl ow in and aliquoting of daughter specimen tubes, fol- vaso-occlusive disorders. Dr. Lee-Lewandrowski lowed by analysis on consolidated instrument received her Ph.D. in chemistry from Brown platforms. Another major innovation led by Dr. University in 1986 and served as a postdoctoral Dighe in 2009 was the development of a com- fellow in clinical chemistry at Hartford Hospital puter interface between the Sunquest laboratory and at the Center for Blood Research in Boston. information system and the hospital provider She received an M.P.H. in Health Care Manage- order entry system. Th is interface eliminated ment from the Harvard School of Public Health the need for handwritten paper requisitions and in 1993 and joined the staff of the MGH in 1999. permitted specimen tubes to be labeled with bar She is an Assistant in Chemistry, Assistant Pro- codes directly on the inpatient care units. fessor at HMS, and Codirector of the Clinical Dr. Laposata also developed laboratory con- Research Core Laboratory. Her scientifi c inter- sultative services, the fi rst such service being ests include the evaluation of rapid point-of- a coagulation consult service run by clinical care technologies and outcomes studies of new pathologists that provided laboratory interpreta- diagnostic technologies. Dr. Murali came to tions on complex coagulation abnormalities and the MGH in 2002 after serving on the faculty also assisted physicians in test selection. Other of SUNY Brooklyn in Medicine and Allergy/ laboratory-based consultative services included Immunology and SUNY Stony Brook as the clinical immunology (protein electrophoresis and Training Program Director in Allergy/Immu- antinuclear antibodies), hemoglobin electropho- nology. At the MGH he has a dual role in the resis, and toxicology. In 2008 Dr. Laposata left Allergy/Immunology division and Pathology, the MGH to become the Executive Vice Chair of where he is Director of the Immunology Labora- Pathology and Professor of Medicine at Vander- tory in the Core Lab. His clinical interests are in bilt University School of Medicine. immunodefi ciency diseases, urticaria, and mono- With the appointment of Dr. David Louis as clonal gammopathies. Dr. Sluss came to the Chief of the MGH Pathology Service in 2006 MGH in 1991 to study reproductive endocrinol- (chapter 25), the Division of Laboratory Medicine ogy, direct the Immunoassay Core Research Lab,

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Figure 20.9 MGH Core Laboratory, 2010. Seated, left to right: Elizabeth Lee-Lewandrowski, Aliyah Sohani, Donna MacMillan. Standing: Patrick Sluss, Elizabeth Van Cott, John Higgins, Mandakolathur Murali, Anand Dighe, Kent Lewandrowski, James Flood.

and manage the Medicine laboratory for infertil- the MGH Pathology staff in 1997, after complet- ity testing. He is an Associate Professor at HMS ing her residency at MGH. She is the Director of with academic interests in biomarker discovery the Coagulation Lab within the Core Labs. She and development, and he is the Codirector of provides a consult service for patients with coag- the Clinical Research Core Laboratory and the ulation disorders, including individualized test MGH Director of the Partners’ Biorepository for interpretations for complex coagulation cases. Medical Discovery. He also serves as the Assistant Another major development in the clinical Director for the immunodiagnostics test menu in laboratory services of the MGH during the 1990– the Core Laboratory. Dr. Sohani graduated from 2010 period was the emergence of bedside labora- HMS and came to MGH Pathology as a resident tory testing performed by physicians and nurses in 2001. She was appointed to the staff in 2007 throughout the hospital and outpatient clinics and serves as the Director of the Hematology Lab (point-of-care testing, or POCT). Limited forms and is interested in hematopathology, laboratory of POCT had existed for decades at the MGH, hematology, and coagulation (thus overlapping including testing for fecal occult blood and dip- the traditional domains of anatomical and clini- stick urinalysis. Indeed, as described earlier, labo- cal pathology), and the delivery of pathology ratory testing performed by physicians and house services in resource-challenged settings. Dr. Van staff was the norm in the early years of the hospi- Cott graduated from HMS and was appointed to tal. Th e growth of POCT was initially catalyzed

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by the introduction of bedside glucose testing for system and highly automated instrumentation. the routine management of patients with diabe- Th e focus of the laboratories has also changed tes mellitus. Th e use of hand-held bedside glucose from small facilities providing services to a select meters rapidly spread throughout the hospital group of specialists to an organization that pro- in the early 1990s, becoming a standard of care. vides comprehensive laboratory services across Over the ensuing two decades, POCT expanded the MGH campus. and by 2009 approximately 650,000 tests per year were being performed at the point of care; there Conclusion were 26 tests on the menu. One area where the Th e history of the clinical laboratories at the MGH became a recognized national leader was MGH is remarkable and mirrors the evolution in Emergency Department (ED) POCT. In 2001 of medicine over the past two centuries. Early a satellite laboratory was established in the ED endeavors in the laboratory resulted from the to provide rapid on-site testing to improve ED intellectual interests of a select group of physicians effi ciency, reduce ED length of stay, and increase who were beginning to apply scientifi c principles the number of patients who could be sent home to the understanding of human disease. Th is was directly from the ED, thus avoiding unnecessary followed by investigators in translational medi- admissions. Th e ED Laboratory was the fi rst in cine seeking to apply scientifi c discoveries to the the country to perform rapid whole blood car- practical diagnosis and treatment of disease. And diac marker testing for the evaluation of patients the most recent phase involved physicians specifi - with acute coronary syndromes. cally trained in laboratory medicine transforming In 2011 tests are ordered online in the Physi- the laboratories into a coordinated and effi cient cian Order Entry (POE) system. Th e orders are hospital system. placed in the laboratory information system Despite the dramatic changes that have (LIS) and given an accession number, and labels occurred over the years in laboratory operations, are printed on the patient units. Th e labels indi- some things remain unchanged to this day. For cate the specimen tube type, patient demograph- example, although the CBC and urinalysis have ics, and laboratory tests to be performed. When been automated, cell diff erentials and urine sedi- the specimens are collected by the unit staff , the ments, even after image analysis, still require the labels are placed on the containers and they are expertise of a trained medical technologist for sent to the laboratory. Laboratory staff acknowl- review. Changes in technology have also produced edge receipt of the specimens in the LIS and new specialties in the medical technology profes- place them on the automation line for processing sion, including informatics, automation, molecu- and analysis. Th e automated line captures qual- lar diagnostics, and operations. Undoubtedly the ity control data and patient test results, followed future will produce more changes, further evolu- by validation and release to the patient electronic tion, and progressive improvements in the ability medical record (EMR). of the clinical laboratory to improve patient care. In summary, the years from 1990 to 2010 wit- nessed a transformation in the MGH clinical References laboratories. Starting from a group of isolated 1. Washburn FA. Th e Massachusetts General Hospi- specialized laboratories with no administrative tal: Its Development, 1900–1935. Boston: Houghton coordination, the clinical laboratories were inte- Miffl in, 1939. grated into a single division within Pathology 2. Myers GW. History of the Massachusetts General and consolidated into a contiguous facility on Hospital, June, 1872 to December, 1900. Boston: Gray 5 with a common laboratory information Griffi th-Stillings Press, 1929.

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