After relating how Horace Walpole came to coin the word "serendipity" in 1754, he cites some of the better-known examples of this phenomenon: Columbus's ...
1318
EDITORIALS AND ANNOTATIONS
THE CANADIAN MEDICAL ASSOCIATION
JOURNAL LE JOURNAL DE L'ASSOCIATION MEDICALE CANADIENNE
published weekly by THE CANADIAN MEDICAL ASSOCIATIONL'ASSOCIATION MEDICALE CANADIENNE
Editor, C.M.A. Publications: DONALD C. GRAHAM, M.D., F.R.G.P.[G]
Associate Editors: GORDON T. DIcKINSON, MA., M.D.
JOHN 0. GODDEN, M.D., G.M., M.Sc.(Med.) Managing Editor: A. D. KELLY, M.B., D.Sc., LL.D.
Assistant Editor: ROBERT L. RANDALL Advertising Manager: THOMAS L. WELLS Editorial Offices: 150 ST. GEORGE ST., TORONTO
DISCOVERIES IN PATHOLOGY D URING the eighteenth and first part of the nineteenth centuries, discoveries in pathology were based upon morphological description and came from the association of structural defects found during postmortem examinations with diseases or lesions recognized during life. During this period Morgagni, Bright, Virchow and others laid the foundations of morbid anatomy and established a form of investigation which continues to provide valuable information. However, morbid anatomical studies alone offered relatively little understanding of the causes of disease and it was only with the development of knowledge about microbes, antigens and antibodies, nutritional factors, and so on, that a fuller appreciation of disease etiology became possible. During the present century, striking advances have been made in every branch of pathology, and the causes of many disorders have been established. Although knowledge about the pathogenesis of many derangements is still inadequate, the mechanism by which certain diseases are produced is now known with an astonishing degree of precision. For example, sickle cell anemia, first described by Herrick in 1910, is now of all human disorders one of the best understood. Not only is its mode of inheritance and geographical distribution clearly appreciated but the specffic chemical defect in the hemoglobin molecule has been identified. On the other hand, there are other diseases about which much more information is needed and this group includes two of the most common causes of death, namely, atherosclerosis and cancer. Moreover, there are many other disorders, such as multiple sclerosis, 'about which we remain distressingly ignorant and still others about which we have only partial information. For instance, although much has been learned about tuberculosis since Koch's discovery of the causative organism in 1882, we
Canad. Med. Ass. J. June 19, 1965, vol. 92
still do not understand the immune mechanism which plays an important role in this disease. The immense growth of scientffic knowledge during the last two centuries has led to the creation of numerous separate disciplines within the broad field of science. This understandable development has had and continues to have highly regrettable repercussions in the areas of research and teaching. Fortunately most experienced scientists now recognize the grave hazards of "departmentalism" and appreciate the essential interdependence of all scientific disciplines. If the differences in technique used are discounted, one finds that discoveries in the various branches of science are made in the same general fashion. Not infrequently a discovery arises from a chance observation made during "routine" work or during the course of experimental studies which at the outset had a very different object in view. On the other hand, discovery may 'be the rational product of carefully designed, methodical research work. The observation, however made, may concern fundamental issues of great signfficance to science generally, or may be a small matter seemingly relevant to only a minor part of an applied field. Much has been written about the respective merit of the various forms of investigative work. Without question the type of research work which carries the highest prestige at the present time is fundamental work in which the investigator develops his research in an appropriately logical fashion and employs elegant techniqu.s which give clear answers to the questions posed. However, this pattern of work can only be performed from a firmly established corpus of knowledge and this basis of factual information is often gained in an empirical fashion. The most able investigators are always ready to observe the unexpected, to seize the chance observation and to develop it as far as possible. In his delightful volume, "The Way of an Investigator", Cannon1 considers the vital role of "hunches" and serendipity in advancing knowledge. After relating how Horace Walpole came to coin the word "serendipity" in 1754, he cites some of the better-known examples of this phenomenon: Columbus's discovery of the New World, the chance observation by Galvani that initiated the science of electrophysiology, Claude Bernard's discovery that the passage of blood into different regions of the body is partly controlled by the nervous system, and Fleming's observation that a mould may have a powerful antibacterial effect. A complete catalogue of important chance discoveries would be of formidable length and would certainly disturb the cosy world of the man who despises serendipity. Of course, an investigator will only be able to take advantage of the chance occurrence or fortunate accident if he is receptive, alert and intelligent. As Pasteur remarked, "Dans les champs de l'observation, le hasard ne favorise que les esprits pr6par6s."
EDITORIALS AND ANNOTATIONS
Canad. Med. Ass. .* June 19, 1965, vol. 92
If one accepts pathology as being the science of disease, one realizes that vitally important contributions to pathology are continually being made by workers in "non-medical" disciplines, as well as by those in the more closely allied medical sciences. Although few geneticists or chemists would admit to being pathologists, their observations are often of great significance in the understanding of disease. Similarly, of course, pathologists have made and continue to make important discoveries in other branches of science. This issue of the journal contains two interesting contributions, by pathologists, about the carotid body and similar structures found in other parts of the human frame. Although there has been much dispute about the origin and function of these structures, in recent years most embryologists have come to regard the carotid bodies as being derived principally from mesoderm, and physiologists usually hold that they are chemoreceptors which by reflex stimulation of respiratory activity help to control the chemical composition of the blood. Karnauchow in presenting a pathologist's view of these fascinating structures (p. 1298) approached his task by making an extensive and critical survey of the available literature and then considering wb.t general information can be derived about their nature from a study of carotid body tumours and of histologically similar tumours arising elsewhere. In his opinion carotid bodies are of ectodermal origin and are probably endocrine in function, and by using paper chromatography he has been able to demonstrate both adrenaline and noradrenaline in extracts of several normal carotid bodies. In the introduction to his paper (p. 1303), Elliott argues that because primary tumours microscopically similar to carotid body tumours occasionally develop in the human abdomen, particularly in the mesentery of the small intestine, it is likely that glomera normally occur there. He therefore examined the retroperitoneal adipose tissue near the origin of the superior mesenteric artery and in two-thirds of his specimens discovered minute bodies whose microscopical structure closely resembles that of normal carotid bodies. It is of considerable interest that Elliott also considers the possibility that these structures may have an endocrine function. These two articles are further examples of the refreshing contribution that pathologists may make to normal anatomy and physiology. Both raise interesting problems, question certain conventionally held views, and will undoubtedly stimulate further investigation of these insufficiently studied structures. REFERENCE
1. CANNON, W. B.: The way of an investigator: a scientist's experiences in medical research, W. W. Norton & Co. Inc., New York. 1945.
1319
A BARE COMPLICATION OF COUMARINCONGENER ANTICOAGULANT THERAPY A ..E complication of coumarin-congener coagulant therapy has been brought to notice by Nalbandian et al. in a report published
recently in the Journal of the American Medical Association.' Although well documented in the foreign literature, it has been almost unknown in the American literature. This complication is characterized by a series of skin lesions-petechiae, ecchymoses, and hemorrhagic infarcts-at random sites, occurring between the third and the tenth day of anticoagulant therapy. These lesions have been associated only with the use of coumarin congeners, which include bishydroxycoumarin, phenprocoumon, phenindione, acenocoumarol, ethyl biscoumacetate, 3,3-ethyl-bis- ( 4-oxycoumarin) and sodium warfarin. Sodium heparin has not been implicated. In a typical history a patient, most often a woman and frequently obese, presents with thrombophlebitis or pulmonary embolism, or both, as the indication for anticoagulant therapy. Within a short interval after initiation of anticoagulant therapy (in 90% within the third to the sixth day) there is a sudden onset of painful hemorrhagic changes in unpredictable skin sites, most often over the lower half of the body. Ecchymotic discoloration and edema of the skin may be manifested initially or following the appearance of petechiae. A morphologic spectrum is apparent, which progresses in some cases to gangrenous necrosis, eschar, slough and tissue defect. A small proportion of such patients have only pain, fleeting erythema, and petechial hemorrhages. Depending on the degree of severity, the lesion may subside without residual defect, heal by granulation tissue or by cicatrization, or require debridement and skin grafting, or even, depending on the site, amputalion. Prior to the reporting of three additional cases by Nalbandian et al., 87 cases of this nature had been described in the world literature. Of these, 83 were in foreign-language publications (Dutch, German, French and Scandinavian). The details of 62 of the 87 cases were available to Nalbandian et al. for analysis, along with the three of their own. Review of these data revealed that women were affected in 60 of the 65 cases. The age range of these subjects was from 16 to 93 years. Hemorrhagic manifestations at sites or in systems other than skin were exceptional. Except in one patient all dosages of anticoagulants were within accepted standard dosage schedules. The outcome was fatal in six.. Further, none of the authors cited by Nalbandian et al. believed that there was any etiological relation between depressed prothrombin levels and the skin lesions. Biopsy and postmortem studies, where performed in the 65 cases under review, revealed that in the skin the arteries were spared while the capillaries
