Hematology

Hematology is the medical specialty that deals with conditions of the blood and blood-forming organs. Plentiful in supply and relatively easy to access, the blood is a tissue well suited to manipulation and investigation. Nineteenth century innovations in microscopy, such as the introduction of new staining techniques and phase-contrast methods, brought great advances in analysis of the blood. Such advances, in combination with the massproduction of the relatively easy to use hemocytometer and hemoglobinometer (used for measuring the size and number of blood cells and hemoglobin concentration, respectively), meant that the morphological and quantitative analysis of the blood became a fashionable part of practice for many early twentieth century physicians, especially those wishing to demonstrate familiarity with the latest methods in ‘‘‘scientific medicine,’’ reflecting and stimulating changes in medical practice and research more widely. It was during this time in North America and Europe that new institutional and intellectual ties between clinical medicine and basic science were forged, dramatically affecting the nature of clinical research. The study of the form and functions of the blood in health and disease was a popular subject of research, attracting the attention of chemists and pathologists, research-oriented clinicians, and chemical physiologists.
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Similarly, as knowledge of the blood and its constituents increased, so routine diagnostic analysis of the blood became a central part of the work of the many new hospital laboratories springing up in this period across Europe and North America. Between the mid-nineteenth and mid-twentieth centuries, research effort in hematology was particularly focused on the causes and treatment of the anemias. These were conditions commonly seen on the wards, which often provided great potential for analysis using the latest technologies. Sickle cell anemia among African–Americans, for instance, was formally identified by Chicago physician James Herrick in 1910, but as a rare disease found solely in members of an underprivileged minority population, it did not initially trigger much clinical or biological interest in the U.S., and still less in Europe, with its tiny black population. Nonetheless, by the 1930s, sickle cell anemia, along with thalassemia, another inherited hemoglobinopathy (first identified as a specific disease in 1925 by the Detroit pediatric physicians Thomas Cooley and Pearl Lee), was recognized as a genetically linked condition, and as such was fitted well in the growth of interest in genetic and molecular views of disease in the twentieth century. In 1945, chemist Linus Pauling and his new medicallytrained graduate student Harvey Itano took up the problem of sickling in red blood cells as a tool through which to explore the chemical nature of hemoglobin, making sickle cell anemia the first disease to be fully described on a molecular level. The link between iron deficiency and anemia, the root of one of the commonest of all nutritional deficiencies, was first made by Gustav von Bunge, Professor of Physiological Chemistry at the University of Basle in 1902. It was not until the 1930s, however, that British physicians Leslie Witts, D.T. Davies, and Helen MacKay each confirmed the role of nutritional iron in the replacement of iron contained in hemoglobin, and discussed the dietary lack or gastric malabsorption of this iron as leading to a specific disease process. In other anemia research, dietary treatment was also producing a great deal of research activity. In 1925 the Rochester physiologists George Whipple and Frieda Robscheit-Robbins published results showing that administration of beef liver to dogs with severe experimental anemia markedly increased the rate of blood regeneration, and they discussed the possible applications of this work to patients with pernicious anemia. Their work was complemented on the clinical side by George Minot and William Murphy, two Harvard medical school physicians, who announced in 1926 a dietary treatment for pernicious anemia through the administration of raw liver. As had been the case for insulin treatment for diabetes (discovered a few years earlier), these findings were celebrated as a wonderful example of the power of combined laboratory and bedside research, and in 1934, Whipple, Minot and Murphy were awarded the Nobel Prize in Medicine for their work. The antianemic factor in liver was isolated and identified as vitamin B12 in 1948 by two teams working independently, one British, led by E. Lester Smith, head of Glaxo’s biochemistry department, and one American, led by Merck’s director of biochemistry, Karl Folkers. The vitamin’s chemical structure was worked out during the mid-1950s by Dorothy Hodgkin, the Oxford x-ray crystallographer, for which work she received the Nobel Prize in Chemistry in 1964.

The absence of some ‘‘intrinsic factor,’’ (i.e., a substance required to absorb the anti-anemic factor), was first proposed by William Castle to be the underlying cause of pernicious anemia arising from his work at the Boston City Hospital during the 1930s (Castle also contributed significantly to studies of hypochromic anemia and iron deficiency ongoing there at this time also).

Castle’s idea stimulated enormous amounts of further hematological research aimed at the isolation and identification of this mysterious entity, and then, it was hoped, the development of a cure for pernicious anemia. Today, the disease remains incurable but treatable, and is now understood as an autoimmune disease. The 1930s also saw the introduction of a pioneering method of quantitative analysis of the blood, devised by the U.S. physician Maxwell Wintrobe, making use of his new invention, the ‘‘Wintrobe tube,’’ designed to measure the volume of packed red cells and erythrocyte sedimentation rate. From this analysis, Wintrobe produced a classification of the anemias that endures to the present day.

If anemia defined the study and practice of hematology in the first half of the twentieth century, then advances in the understanding of blood malignancy (the leukemias and lymphomas) and the introduction of effective chemotherapies firmly established hematology as a formal specialty in the post-World War II years. The first Professional hematological society, the International Society of Hematology, was founded in 1946, followed by the American Society of Hematology in 1954, and then several national societies across Europe and Asia. New journals such as Blood (1946), The British Journal of Haematology (1955) and Progress in Hematology (1956) became crucial professional vehicles for the nascent specialty. The new oncology and pediatric oncology bodies and journals emerging during the 1960s and 1970s further extended the professional interactions of hematologists.
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By the end of the twentieth century, a career in hematology required first training as either a physician or a pathologist, and involved some or all of the following: the management of blood products and derivatives; the administration of immunosuppressives, chemotherapies, anticoagulants and antithrombotic agents; and supportive care for a range of systemic diseases. On the research side, hematologists are actively engaged in research on several fronts including anemia, cancer and chemotherapy, blood typing and blood products, pain management studies, and stem cell therapy.