Henry Dale

Chemical structure and sympathomimetic action of amines

Introductory. The elucidation of the structure of the active principle of the stupra-renal medulla by the work of Abell, v. Fifirth2, Takamine3, Aldrich4, Pauly5, and Jowett6, and its synthesis by Stolz 7 and by Dakin8, almost simultaneously, led to the physiological investigation of substances nearly related to it in chemical structure. Loewi and Meyer9, working with Stolzs preparations, investigated a number of ketones of the general formula (OH)2C5H3 . CO . CH2NR1R2 and the corresponding secondary alcohols (OH)2C.H3.CHOH. CHNR,R2, obtaine(d by reduction of the ketones, among these reduction products

Wartime Arrangements for International Biological Standards

The International Standards for l emedies of which the strength has to be measured by biological methods came into being between the two world wars, through action by the Health Organization of the League of Nations. The work was by no means limited, however, to the nations that had joined the League. Important shares in the enterprise, which began in 1921 on Dr. Madsens initiative, were taken at the outset by experts from the countries that had not yet been admitted, and during the whole period by those from the United States of America. Even when Germany and her associates later withdrew from the League the international standards remained in use among their men of science, though without official recognition, and German industry continued to make important contributions to the materials required for the preparation of new standards.

Otto Loewi. 1873-1961

Otto Loewi, born on 3 June 1873, in Frankfurt am Main, was the son of Jakob Loewi, a wine-merchant of that city, by his wife, Anna Willstaedter. Throughout his life Otto retained very happy memories of his childhood and schooldays. For the nine years from 1881 to 1890 he attended in Frankfurt a Gymnasium of the old style, in which the studies were centred on the classical languages—Latin being studied for the whole nine and Greek for the six later years. He accepted for himself the not unfamiliar view that such an emphasis in education, during the formative years of boyhood, would have had a specially favourable influence on his personality, and on his general attitude to life and learning. In an ‘autobiographic sketch’, published in the year before he died, he recorded that, during these nine years at the Gymnasium, he obtained ‘fairly good marks’ in these literary subjects, but ‘poor marks’ in physics and mathematics. Without attempting to assess the respective shares in the result, of inborn aptitudes and of a particular educational routine, it may at least be accepted as a fact, that Loewi exhibited in later life an unusually wide range of knowledge and interests, for one whose main career and activities were concerned with one faculty of the natural sciences.

Advances in medicinal therapeutics.

I think that our successors, viewing the times in which we live from the longer perspective of history, are likely to recognize the first half of the twentieth century as the period in which civilization first began to feel, for good or ill, the full impact of progress in the natural sciences. The application of scientific knowledge and methods to mans common activities and needs can be traced, of course, to much earlier beginnings; but the richness of the nineteenth centurys closing decade in major discoveries, of the kind from which science advances with a fresh impetus and in new directions, seems to have caused a sudden acceleration of this process to begin about the turn of the century. In no department of knowledge and practice has this change, since 1900, been more conspicuous or more rapidly progressive than in the general field of medicine. The end of the nineteenth century found medicine still a body of largely empirical knowledge, growing mainly by slow accumulation from the direct study of disease at the bedside and of its results in the post-mortem room-a method which in that century had yielded rich harvests indeed; but these had been rare and had ripened but slowly. In 1900, when I entered upon my own undergraduate clinical studies, experimental research had begun to exercise an influence on clinical practice in certain directions, and especially on some aspects of diagnosis-several decades earlier, indeed, it had had Listers revolution of surgical methods to its credit-but the relation, in general, between the laboratories and the wards remained one of critical aloofness on both sides. It was possible, and not unreasonable, for the student then entering the wards to receive,

Edward Mellanby. 1884-1955

Death came suddenly, and without recognized warning, to Sir Edward Mellanby on 30 January 1955, before he had completed his 71st year. Nearly six years earlier he had retired, on reaching the official age-limit, from the Secretaryship of the Medical Research Council, which he had held for 16 years. During this period the range and the influence of the Council’s activities for the promotion and support of medical research had undergone a most notable expansion, primarily in the United Kingdom, but widely beyond it also in the British Commonwealth; and Mellanby’s enlightened and resourceful enterprise in proposal and planning, and his vigorous drive in administrative action, had undoubtedly been dominant factors in this remarkable development. Like his only predecessor in the appointment, the late Walter Morley Fletcher, Mellanby had been the Council’s chief executive officer in much more than a merely official sense. Yet, during all the years in which he had carried that heavy load of official responsibility, he had succeeded in maintaining a direct and personal activity in the researches which had so long provided for him, and also for his devoted wife and scientific partner, the central aim and interest of their joint working lives.

A Prospect in Therapeutics

One of the clear impressions left by my student days in hospital, at the beginning of the present century, is that of surprise and disappointment at the lack of conviction, and even of interest, which our teachers showed in medicinal treatment, in contrast to the care and enthusiasm which they devoted to diagnosis. I suppose that before I entered the wards I had assumed, with the world at large, that a correct diagnosis would regularly enable an appropriate and effective remedy to be applied. It was disappointing to discover that this was so rarely the result, and that treatment would so often be prescribed with no better hope than to make the patient easier by alleviation of his symptoms, leaving Nature to deal, if possible, with the cause of the trouble. It is clearer to me in retrospect than it was at the time that there were very few remedies then which were even expected to deal with the causes of disease; for knowledge of those causes was itself a new thing, though it was beginning to come in a flood from the fresh outburst of experimental medicine in the last quarter of the nineteenth century. I think, indeed, that the period which 1 thus recall probably represented about the low-water mark of interest and confidence in the remedial value of drugs. Some of the established remedies for symptoms were clearly invaluable for their own purposes-digitalis, for example, morphine, cocaine, the bromides, and the general anaesthetics. The same was true of the use of salicylates in acute rheumatism, though it was not clear whether this dealt with the symptoms only or with the cause of the disease; nor can it be so even now until the cause of acute rheumatism is established beyond doubt. There were, indeed, a few drugs even then in use of which we can say, in the light of present knowledge, that their remedial value was due to action on the infective causes of the diseases in which they were used-cinchona and quinine for malaria, ipecacuanha (though not yet emetine) for dysentery, mercury and theiodides for syphilis. But at that time the knowledge of the malaria parasites was almost a novelty, the dysenteries were imperfectly differentiated, and the discovery of the spirochaete of syphilis was still in the future. The use of these remedies, like that of so many others, was then still based on the tradition of past centuries. Emergence of Remedies of New Types Out of the experimental researches which were bringing to light the causes of disease, and thus weakening the credit of drugs which could do no more than modify or alleviate symptoms, there were emerging, on the other hand, remedies of new types-not drugs unnatural to the body, but natural principles which would directly repair its deficiencies, or would supplement and reinforce its protective responses to infections.

Thomas Addison: Pioneer of Endocrinology.

Thomas Addison was second in that matchless succession of physicians and morbid anatomists-Richard Bright, Thomas Addison, William Gull, and Samuel Wilkswhose work at Guys Hospital in the earlier and middle years of the nineteenth century raised to such heights the reputation of this school as a great centre of medical teaching and investigation, and c o n t r i buted so much to the foundation of the ........

Physiological Basis of Neuromuscular Disorders

fo-days discussion is to deal with the bearing of recent physiological observations, and of the interpretations which have been applied to them, on clinical studies of neuromuscular disorders. The choice of myself as opener, and of subjects by those who are to follow me as invited contributors, would appear to direct our discussion chiefly to the clinical applications of the large and growing body of evidence for the transmission of effects from the endings of nerve fibres to contiguous responsive cells by the liberation of chemical transmitters.

Thomas Renton Elliott, 1877-1961

T. R. Elliott, born in 1877, was elected to the Fellowship of The Royal Society in 1913, before he was 36 years old; and his election, thus rather early in his career, was certainly made in recognition of the quite unusual distinction and brilliant promise of the experimental researches in physiology, which he had carried out at Cambridge by 1906, and of which he had published the results, with his conclusions, in several remarkable papers, between 1904 and 1907. College and University post-graduate studentships had enabled him thus to stay in Cambridge for the five years following his graduation in 1901, and there to concentrate his activities and interests on these experimental studies. And then, in 1906, at the age of 29, he left Cambridge to enter as a student at University College Hospital, London, with the immediate purpose of completing his clinical curriculum and his qualifying graduation in medicine. Among those who had followed and admired the progress of what he had already then achieved, there were probably many to whom it would have seemed natural to expect that the years of clinical study and qualification would prove for him, as they had done for others, to be an interlude, the experience gained in which would strengthen his equipment and his claim for advancement in an academic career, most obviously perhaps in physiology, but, in any case, in one or another of the experimental disciplines which had by then already become recognized as contributory to the scientific background of medicine.

Percival Hartley. 1881-1957

Pergival Hartley was born on 28 May 1881 at Calverley, near Leeds, as second son and third of the four children of William Thompson Hartley and his wife, whose maiden name had been Grimshaw. The father, W. J. Hartley, was in business as a manufacturer of woollen cloth. From notes which his son Percival has left, it may be gathered that he was a failure in this business of his own, but, by way of contrast, very successful in his activities on behalf of his fellow townsmen, as a social worker, a magistrate and a member of the local Council, of which he became the Chairman. Percival Hartley’s mother also came of people connected with the local industry, an ancestor of hers having built and owned one of the first mills to make woollen cloth; and Hartley evidently thought of her as having had a stronger and more enterprising influence than that of his father, on the prospects of their family. ‘She managed our schooling’, he writes, ‘and made the decisions which mattered, about schools, colleges etc. She encouraged us, and me particularly, to “Strike out”, try new ventures, etc. She encouraged change and trying things, while my father always “played for safety” .’ Later he appears to have recognized more clearly that his father also had plans and ambitions for the family, but that these were largely determined by the admiration and respect which he had formed for J. R. Raper, also a manufacturer of woollen cloth, but a more successful one.