William Osler's Legacy and his Contribution to Haematology

William Osler (1849–1919) is generally regarded as one of the greatest and most admired physicians in the history of medicine. An outstanding clinician, he possessed extraordinary charm which inspired many pupils. Osler stressed bedside teaching, hard work, medical history and lifelong learning. As Professor of Medicine at four institutions in three countries, he exerted a profound influence on medical education. A prolific writer, his textbook became the most popular and widely read treatise on medicine in the world. His humanistic philosophy was reflected in all aspects of his life. Osler blended the art and science of medicine perhaps better than anyone else and remains a valuable role model for students and physicians. Osler's early experience with the microscope as a schoolboy led to important contributions to haematology. He was among the first to recognize platelets as the third formed element of the blood; he documented their importance in thrombosis. His early studies on pernicious anaemia have been largely neglected, but his thorough descriptions of polycythaemia vera and hereditary haemorrhagic telangiectasia popularized both entities. Most significant of all, Osler brought the microscope to the clinic and emphasized the value of examination of the blood in clinical diagnosis. Osler occupies a unique position in the history of medicine. He is generally acknowledged as one of the most outstanding clinicians and teachers of all time (Dana, 1919; Cushing, 1925; Abbott, 1926; Reid, 1931; Bailey, 1993; Stone, 1995). Many of Osler's writings (Osler, 1904a, 1907a, 1908a, 1913, 1921; Camac, 1906; Verney, 1960; McGovern & Roland, 1969, 1985; Roland, 1982; Nation, 1987; Hinohara & Niki, 2001; Silverman et al, 2003) have inspired and been cherished by medical students and physicians throughout the world. His close personal relationship with students and colleagues has been amply documented (Pratt, 1949; Nation & McGovern, 1980; Howard, 1983; Golden, 1992a). Commemorative issues of several journals have appeared in his honour (Osler Memorial Issue, 1949; William Osler Anniversary Issue, 1949; Roland, 1969), a number of bibliographies of his writings have been published (Blogg, 1921; Abbott, 1939; Nation et al, 1976; Golden & Roland, 1988), and his likeness has been preserved on many portraits, busts and medals (Sakula, 1991). A new biography appeared in the sesquicentennial year of his birth (Bliss, 1999), the first full-length account of Osler's life since Cushing's Pulitzer prize-winning treatise published in 1925. The Osler Society of McGill University was founded in 1921, the Osler Club of London in 1928, the American Osler Society in 1970 (Barondess et al, 1985; Barondess & Roland, 1994, 2002) and the Japanese Osler Society in 1983. In May 2003, a joint meeting of the American, London and Japanese Osler organizations was held in Edinburgh, UK. Thus, Osler remains one of the most revered physicians of modern times (Golden, 1999a). William Osler was born in Bond Head near Toronto in 1849, the eighth of nine children (Table I) (Talbott, 1969; Roland, 1984; Bliss, 1999). His mother lived past the age of 100 years; his father was an Anglican clergyman. As a bright, high-spirited youngster, Willie got into his fair share of trouble – he was expelled from grammar school for abusive language and once filled a schoolroom with geese after moving the desks to an attic. At private school, he met Reverend W. A. Johnson, who introduced him to biology and the microscope. This interest in microscopy was to become one of the dominant themes of his career. He enrolled in Trinity College at Toronto and originally planned to follow his father into the clergy. After being influenced by a physician, Dr James Bovell, Osler switched to medicine (Silverman, 1993). He entered Toronto Medical School and transferred to McGill for his final 2 years. There, he came into contact with the well-known clinician and teacher, R. Palmer Howard. Johnson, Bovell and Howard were the three teachers to whom Osler later dedicated his textbook. He received his MD degree in 1872 from McGill and then travelled to England and continental Europe. Osler's experience abroad made him a proponent of postgraduate travel. His trip was the first of what later became known as ‘brain-dusting excursions’. He spent 17 months in London at University College Hospital in the physiology laboratory of John Burdon Sanderson (whom he would succeed as Regius Professor of Medicine at Oxford 33 years later), during which time he became one of the first to recognize the platelet as the third formed element in the blood and documented the importance of platelets in thrombus formation (Osler, 1886a). He also visited Germany and came into brief contact with the great Rudolph Virchow. On returning to Canada, he began working as a general practitioner. A few months later, he was invited to join the medical faculty at McGill. ‘ No bubble is so iridescent or floats longer than that blown by the successful teacher ’ (Osler, 1911) During his 10 years on the McGill faculty (1874–1884), Osler rose to the rank of professor. He was quickly recognized as an outstanding clinician and stimulating teacher, always emphasizing the role of bedside teaching and observation. He also served as a pathologist to a smallpox hospital, maintained a small private practice and published many papers dealing with various clinical, pathological and veterinary subjects. During this decade, Osler organized medical clubs and achieved unusual popularity engendered by his exemplary conduct and generosity. ‘ Medicine is learned by the bedside and not in the classroom ’ (Thayer, 1931) Osler performed nearly 1000 autopsies; this experience, combined with his knowledge of microscopy, made him well grounded in morbid anatomy and contributed much to his understanding of the natural history of disease and the importance of clinicopathological correlation (Robb-Smith, 1981; Rodin, 1981). ‘ Now the way of life that I preach is a habit to be acquired gradually by long and steady repetition. It is the practice of living for the day only, and for the day's work. Life in day-tight compartments' (Osler, 1913) Osler left Montreal in 1884 to become Professor of Clinical Medicine at the University of Pennsylvania. His reputation and productivity continued to grow in Philadelphia. He gave his famous address, Aequanimitas, to the University of Pennsylvania graduating class in 1889. That year, he became Chief of Medicine at the new Johns Hopkins Hospital and Medical School, where he remained until 1905 (Fig 1). William Osler in 1905. From a photograph by William Notman, Montreal. Reproduced (with permission from the Secretary-Treasurer of the US and Canadian Academy of Pathology) from Abbott (1926). ‘In the physician or surgeon no quality takes rank with imperturbability ’ (Osler, 1904b) Osler was instrumental in establishing Johns Hopkins as the outstanding institution of medical education in the United States (Starr, 1982; Ludmerer, 1985, 1999; Harvey et al, 1989, 1990). He helped to found the new school and was one of the ‘Big Four’ of Hopkins along with Welch, Halsted and Kelly (Southgate, 1989). He introduced the clinical clerkship and created the template of graded responsibility among students and house officers that survives to the present day (Ludmerer, 1985, 1999; Beeson & Maulitz, 1988). He continued to emphasize the importance of direct interaction with patients and careful clinical observation. He stressed the value of medical history and wrote many inspirational essays. For him, the master word in medicine was indeed ‘work’ (Osler, 1904c). During his tenure at Hopkins, Osler acquired an international reputation and became one of the most respected clinicians in the world (Fig 2). Osler at the bedside. From Cushing (1925) (reproduced with the permission of Oxford University Press). ‘ Variability is the law of life, and as no two faces are the same, so no two bodies are alike, and no two individuals react alike and behave alike under the abnormal conditions which we know as disease ’ (Osler, 1904d) ‘ Start out with the conviction that absolute truth is hard to reach in matters relating to our fellow creatures, healthy or diseased, that slips in observation are inevitable even with the best-trained faculties, that errors in judgement must occur in the practice of an art which consists largely in balancing probabilities ’ (Osler, 1904e) In 1892, Osler's textbook, The Principles and Practice of Medicine, appeared and became the leading treatise on general medicine in the world for the next 40 years (Osler, 1892a; Harvey & McKusick, 1967; Beeson, 1986; Fye, 1987; Golden, 1992b). He personally revised the book through seven editions. Two quotations appear in the front of the book: ‘ Experience is fallacious and judgement difficult ’ – Hippocrates: Aphorisms I ‘ And I said of medicine, that this is an art which considers the constitution of the patient, and has principles of action and reasons in each case ’ – Plato: Georgias The misspelling of Gorgias identifies the first printing of the textbook; the error was corrected in the second printing and subsequent editions. The enormous influence and popularity of the textbook were evident from its sales and its translation into French, German, Russian, Spanish, Portuguese and Chinese editions. It was also indirectly responsible for the formation of the Rockefeller Institute for Medical Research (Beeson, 1986; Golden, 1992b; Edelson, 1994). The textbook emphasized aetiology, pathogenesis and diagnosis, and reflected Osler's great knowledge of clinical medicine and pathology. Lucidly written with many historical references, it was said that Osler ‘succeeded in making a scientific treatise literature’. However, he became known as a therapeutic nihilist (Thomas, 1983; Beeson, 1986; Beeson & Maulitz, 1988). On balance, one should recall that not many effective medical treatments existed in the latter part of the nineteenth century. ‘ Do not rashly use every new product of which the peripatetic siren sings. Consider what surprising reactions may occur in the laboratory from the mixing of unknown substances. Be as considerate of your patient and yourself as you are of the test-tube ’ (Thayer, 1931) Grace Revere Osler was the great granddaughter of Paul Revere and the widow of Osler's friend, Doctor Samuel W. Gross, the Philadelphia surgeon who helped recruit Osler to the University of Pennsylvania (Muirhead, 1931; Harrell, 1982, 1985; Wagner, 1985). Grace and William were married in May 1892, shortly after publication of the textbook. They had two children, Paul Revere who survived only briefly, and Edward Revere, born in 1895. Osler left Baltimore in 1905 to assume his new position as Regius Professor of Medicine at Oxford (replacing his mentor, Burdon Sanderson) where he lived for the remainder of his life (Malloch, 1921; Cushing, 1925; Fye, 1989; Bliss, 1999). He thought that Oxford would offer a more relaxing atmosphere so that he could retire gradually, but he was soon as busy as he had been in Baltimore (Roland, 1984). The Osler home at 13 Norham Gardens became known as the ‘Open Arms’ to students, colleagues and friends. Osler continued to found medical organizations and journals including the Quarterly Journal of Medicine. He served as curator of the Bodleian Library. In the pattern of Virchow, Osler vigorously supported public health and sanitary measures. He continued clinical teaching, collected books, published papers and practised medicine. A baronetcy was conferred on him in 1911. The tragedy of his life occurred in 1917 when his son, Revere, was killed in Flanders in World War I. In 1919, Osler developed pneumonia and died on 29 December (Hinohara, 1993). His last formal presentation was the inaugural address as president of the British Classical Association 6 months before his death (Osler, 1920). A prolific writer, Osler had over 1600 items in his bibliography (Golden & Roland, 1988; Golden, 1999a). His first publication described the appearance of pond water under the microscope (Osler, 1869). His important original observations on blood platelets were made in 1873 when he was 24 years old. Approximately 8% of his publications dealt with haematology, oncology or the microscope. Nearly one-third of his scientific papers were devoted to topics on cardiovascular disease (Pruitt, 1982; Fye, 1985). Osler's clinical investigative and research background provided him with an insightful perspective. ‘ The greater the ignorance the greater the dogmatism ’ (Osler, 1904f) ‘ The philosophies of one age have become the absurdities of the next, and the foolishness of yesterday has become the wisdom of tomorrow ’ (Osler, 1904f) ‘ Thousands of men with keen eyes had watched the heart beat, had seen arteries spurt red blood, had seen the black blood flow from the veins, and they had thought and thought and thought of how the heart beat and how the blood flowed, but all in vain until, in a few simple experiments, the problem of its circulation was demonstrated ’ (Osler, 1911) Osler continually emphasized the importance of bedside teaching and clinical laboratory microscopy, the ongoing necessity to read throughout one's career and the recognition of contributions by previous physicians. He was always in direct contact with students (his chosen epitaph was ‘I taught medical students on the wards’), and often hosted informal meetings with them on Saturday evenings at his home. In Baltimore and Oxford, many were given keys to his front door so that they could take advantage of his outstanding library; these students became known as the ‘Latch Keyers’. ‘ Just as the embryo passes through life of lower grade, before resulting in the thinking man – the ontogeny reproducing the phylogeny – so the career of the medical student follows the evolution of the marvelous knowledge that has made our profession the most helpful of all to humanity ’ (Osler, 1911) ‘ To study the phenomena of disease without books is to sail an uncharted sea, while to study books without patients is not to go to sea at all ’ (Osler, 1904g) Osler cultivated a lifelong interest in the history of medicine and the humanities (Osler, 1921; Fulton, 1949; Bensley & Bates, 1976; Wallis, 1986). His humanistic philosophy and conduct were reflected in all aspects of his life. He emphasized the importance of the classics and of regular reading at bedtime (Osler, 1904a; Rakel, 1988; Bryan, 2002). His personal library contained over 7000 books, which he bequeathed to McGill University (Osler, 1929; The Osler Library, 1979). Always a prankster, he humorously wrote under a pseudonym, Egerton Yorrick Davis, sometimes criticizing his own (i.e. Osler's) writings (Bean, 1966; Nation, 1969; Golden & Roland, 1988; Golden, 1999b). Osler constantly reminded students of the high ideals of the medical profession and the human side of patient care: ‘ Care more particularly for the individual patient than for the special features of the disease ’ (Bean & Bean, 1961a) ‘ To have striven, to have made an effort, to have been true to certain ideals – this alone is worth the struggle ’ (Osler, 1908b) However, Osler was not just a kindly old clinician who liked to teach and write. He recognized the need to be critical of colleagues (Roland, 1974). He applied the latest advances in medicine to the care of his patients – whether it was the use of newly described stains in the interpretation of blood smears or urging the Board of The Johns Hopkins Hospital to acquire an X-ray machine within a few months of Röntgen's first publication announcing its discovery (Conn, 1985). Osler realized that advances in scientific medicine greatly enhanced the clinician's effectiveness in patient care, and he welcomed them (Osler, 1915). It seems likely that Osler would be squarely in the forefront of advances in medical science if he were alive today. ‘ It is astonishing with how little reading a doctor can practice medicine, but it is not astonishing how badly he may do it ’ (Osler, 1904g) ‘ To wrest from nature the secrets which have perplexed philosophers in all ages, to track to their sources the causes of disease, to correlate the vast stores of knowledge, that they may be quickly available for the prevention and cure of disease – these are our ambitions ’ (Osler, 1904f) In this era of ongoing debate on health care reform and delivery, it is essential to keep in mind how patients are cared for, how medical students are taught and how medical science advances through In this Osler's wisdom is and are Osler's on the importance of hard work, close ongoing education and a to the day's the for effective of scientific knowledge in and His and for patients and colleagues are we to His and the that what it to be a Osler old art be but must be the new (Osler, He the art and science of medicine as well as anyone Osler remains a role model for Osler was introduced to the as a by his Reverend Johnson, and his interest developed under the influence of Dr Osler's first publication age was and the microscope (Osler, 1869). In the he has on and under them most of which in and so A for one would a under the microscope before I had it I the of little and as it were in a Reverend and Dr Bovell, Osler acquired a of to with the in after Willie to become a doctor than a of the clergy. After 2 years at the Toronto medical school, he to McGill. His first clinical written while a medical student described the and of a patient with (Osler, Osler's in 1872 dealt with the time he received the MD Osler was an He this to great advantage in his postgraduate study and became a of the value of microscopy in medicine. Osler taught microscopy to students at brought the first microscope to the University of Pennsylvania Hospital and the Clinical at Johns A special meeting of the Johns Hopkins Club was held in at which time a was to the by of Osler's colleagues and meeting of the Johns Hopkins (Fig Dr R. the who the said it was to Dr Osler at a clinical The is out to his microscope that was always his The created R. and to the Johns Hopkins Hospital by Osler's and (reproduced with permission from the Secretary-Treasurer of the US and Canadian Academy of The discovery of platelets several during the and 1949; The first of blood than red and had been by and However, it is that platelets could be seen before when a for that has been with the first of platelets and William an to published a of a in The year, that existed in the blood red and and little that he had recognized a element in the the father of clinical and who taught Osler much microscopy, published an in with a of human blood his interpretation of their was Osler in England to study in Burdon physiology laboratory (Fig he the of various on under the of Edward In at his own blood, Osler's became to which he thought were to the described by 1985). In Osler the blood in and of killed and out that the of from of small bodies which occurred as in the circulation (Osler & were to the of a red His that these occurred as in the blood, which came when the blood was Osler was not what they perhaps and to in the of his On returning to Osler continued his studies of In he on a in which he maintained interest for his life (Osler, He the of bodies in the on heart but also the on the so was platelets and In Osler that a thrombus on an of platelets (Osler, Osler during his postgraduate in London 1926; (reproduced with permission from the Secretary-Treasurer of the US and Canadian Academy of that platelets were that in the blood of living Osler's on but a the (Osler, In Osler was invited to the at the College of and in He the certain in the physiology of blood The three of a of both his own and on blood and (Osler, 1886a). Osler platelet that occurred in blood, which he had described in his 1873 when he the with He that the third or blood was a in blood, from to (Fig number in the blood of a healthy is but their number greatly at of life and with conditions of health and In he it is which the blood a for the so as observation are born in the but appear to it as and are from it before they are so as to be no longer In the third Osler I that the are of and that the an part in their Osler's observations emphasized the role of platelets in and the of and Osler's of I The were the last of Osler's observations on In he part in a held at Johns Hopkins (Osler, that platelets on the of contained Osler that he had seen many but one that William Osler made of the observations that platelets as a of blood and their with thrombus Osler's studies on platelets were his most significant original scientific they have not generally received much – one of in the Cushing biography In the published in they are It is difficult to know which of the patients described by James and during the years after had pernicious anaemia had been anaemia for years before he wrote in its in so and a that the patient can a to his of that which is soon to become so the of clinical and laboratory anaemia was to of the by in a by Samuel In William and Osler a case of pernicious The had been years before by who described it as a new This much interest and also of by Samuel and and Osler's case was the first in which the clinical, and pathological features were described in to little that it was as The patient was a who of and on of the and his and a in his He died of 2 months In the blood, Osler described and in and of the red At a to the and a were The and was filled with red and a This was the first of the (Robb-Smith, 1981; 1985). Osler that was a of but that it was a of the to an he not Osler's of to to the and in ‘ The of the blood in this disease are of your as I know of no disease in which that the red blood important ’ (Osler, In Osler's clinical on in he described the and while the (Osler, not he blood and even was as he that of our Montreal have The of the disease was months with unusual years. & Osler on of the with the clinical features of The patient was a man with of examination the to have the which by Osler was of along with that appeared The red blood was with of which were four times The patient died 6 months later with a red of Osler that the blood platelets were also of the and all and The had a in the and small A from the and Osler all of the A in the is the which all the of the The with the previous by and and that of the of pernicious anaemia profound in the In the of The Principles and Practice of Medicine, the last that he revised Osler that his of over the age of and the disease was more in (Osler, Osler from the anaemia of and his previous with he that with be from He

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