William Henry Howell and Jay McLean: The Experimental Context for the Discovery of Heparin

WILLIAM HENRY HOWELL ANDJAY McLEAN: THE EXPERIMENTAL CONTEXT FOR THE DISCOVERY OF HEPARIN JAMES A. MARCUM* Heparin is a highly sulfated complex carbohydrate which renders blood, in either an in vitro or in vivo state, incoagulable. The polysaccharide is utilized as a pharmacological agent in hospitals around the world to treat patients with bleeding disorders [I]. In his account on the discovery of heparin published posthumously in a symposium honoring investigators for their pioneering work with anticoagulants [2], Jay McLean wrote, "The discovery of heparin came as a result of my determination to accomplish something by my own ability" [3, p. 75]. Although McLean has been credited with the first description ofthe potent anticoagulant [4], Louis B. Jaques, a Canadian biochemist who was part of the original group responsible for the development of heparin as a pharmacological agent, has taken issue with the claim that McLean discovered the polysaccharide [5]. By careful examination of the published literature and by critical analysis ofthe reported data, he argued that the anticoagulant reported by McLean in 1916 was a phospholipid and not the complex carbohydrate later isolated and described by William Henry Howell. Jaques based his assertion on the different solubilities of these compounds: phospholipids in organic solvents and polysaccharides in aqueous solutions. He also cited the work of Silver, Turner, and Tocantins [6], who demonstrated that phospholipids possess anticoagulant activity . Jaques concluded, referencing Selye's work on scientific discovery, that often a discovery in science is credited not to the researcher who solves a problem but to the person who initiates it, and so, "McLean discovered heparin (no more and no less)" [5, p. 352]. Although the ?Department of Philosophy, Boston College, 140 Commonwealth Avenue, Chestnut Hill, Massachusetts 02167-3806, and Department of Pathology, Beth Israel Hospital, Harvard Medical School, 330 Brookline Avenue, Boston, Massachusetts 02215.© 1990 by The University of Chicago. AU rights reserved. 0031-5982/90/3302-0663$01 .00 214 I James A. Marcum ¦ Discovery ofHeparin contributions of McLean, and of his mentor Howell, to the discovery of heparin have been assessed in general terms [7, 8], the original articles published on the anticoagulant have not been reviewed in detail or set within the context of scientific theories of coagulation prevalent in the late nineteenth and early twentieth centuries. To this end, the 1916 paper of McLean will be situated in the milieu of experimental research conducted by Howell and his associates at The Johns Hopkins Medical School, in order to address the issues surrounding the discovery of heparin. I In 1870, Michael Foster was appointed praelector at Trinity College in order to reestablish the importance of experimental physiology in England [9]. At Cambridge, Foster's classes in physiology were popular, and he attracted hardworking associates who were responsible for much of the program's success. Within a rather brief period, he was able to stimulate student interest for physiology as an empirical science by stressing an experimental approach and by requiring students to immerse themselves in the activities of the laboratory. Foster also founded theJournal ofPhysiology, which was vital for communicating results from the young physiology department, as well as from other institutions. Foster's research interest was cardiovascular physiology, and, in 1864, he published a critical review of blood coagulation mechanisms [10]. From his survey of the literature, he identified two components responsible for the deposition of fibrin: globulin and fibrinogen. Foster noted, however, that clotting involved more than just the combination of the two fibrin elements: the conditions under which globulin and fibrinogen joined to form fibrin were also important. From a discussion of the factors and conditions responsible for coagulation, Foster queried: "How is it that blood containing a large amount offibrinogen and a great excess of globulin, that lymph, chyle, and other plasmata, retain their fluidity in their natural living abodes, and yet clot as soon as they are shed?" [10, p. 171]. He next examined the answers, proposed by Richardson, Lister, and Bruecke, to the above question. Foster quickly dismissed the "ammonia" theory of Richardson, who claimed that fibrin was deposited by the release of ammonia from a soluble ammonia-fibrin complex. He cited the work of Thirty, who demonstrated that ammonia was...