558 



NA TURE 



[October 7. 1897 



had been shown by therapeutic observations, made in ignorance 

 of the fact that an iodine-containing organic body was present in 

 the thyroid. Similar considerations apply equally to prepara- 

 tions of arsenic and mercury. It could not but happen that the 

 philosophic point of view ascribed to all these remedies cer- 

 tain quahties which did not in reality reside in them. It is 

 admitted, however, that the idea that as a matter of fact the 

 chemical properties of a substa.nce were of significance in regard 

 to its action was known to Paracelsus. If, therefore, the 

 fanaticism for this idea far overshot the mark, still the re- 

 sults then and afterwards obtained, and, indeed, the whole 

 work of the iatrochemical school was not without therapeutic 

 value. 



The science of experimental pharmacology, which has arisen 

 in our time, might well have contented itself with undertaking 

 to put to the test the therapeutic material already to hand, and 

 to contribute to the elucidation of its mode of action in order 

 to be able to lay down more precisely the limits of its action, 

 and so to lend a helping hand to clinical observation. It could 

 easily have foregone the further empiricism of collecting new 

 materials. But from the moment in which scientific remedies 

 were brought into the domain of therapeutics, its horizon 

 widened. It became necessary to take up and to seek to realise 

 the idea of freeing the mind from empiricism, and of finding the 

 leading principles by which the material of the healing art might 

 be increased in a scientific manner. With the beginning of the 

 attempt to establish this undertaking pharmacodynamics could 

 no longer be satisfied to use merely the results of simple experi- 

 ments upon living animals, but must needs also, with scrupulous 

 attention to pathological principles, regard as its most important 

 factor the representation of the conditions in health and disease 

 as the basis of experimental inquiry. 



In so far as concerns the search after new materials for 

 remedies, one may correctly rely upon the principles of the 

 iatrochemical school. Only those ideas must be excluded 

 which, owing to deficient anatomical knowledge, rank as 

 belonging to humoral pathology in the most rabid sense of 

 the term. The investigators of those days stood also in the 

 shadow of an alchemical environment, but had always before 

 their eyes the endeavour to form an idea as to the nature of 

 matter. For us, modern chemical ideas have created a new 

 world. We know now that the smallest part of a chemical 

 component — let us say, for example, a piece of sugar — is 

 characterised by a special arrangement of the atoms of various 

 elements, and that each change in their relative positions 

 leads to the formation of a substance with new physical pro- 

 perties. The development of chemical research in this direc- 

 tion points to the discovery of innumerable new substances. 

 One single reaction can yield several millions of these, and he 

 who knows how to use the pencil aright can readily, by the con- 

 struction of their formulae on the paper, convince himself that 

 the vast number of hitherto isolated organic substances forms 

 but a minute part of those which can be assumed with safety to 

 be capable of existence. This simple observation teaches us 

 that we are no longer travelling along the route by which digi- 

 talis and the other old remedies of the healing art were made 

 known to us. 



It is very noteworthy that a long period elapsed before atten- 

 tion was paid to these powerful therapeutic adjuvants. It may 

 be acknowledged with great thankfulness that this attention has 

 been directed not only from the medical but also from the 

 chemical side. In this connection, A. W. v. Hofmann correctly 

 points out that after the discovery of so many organic sub- 

 stances some were soon brought into use for the sake of their 

 external properties, while their internal applicability was never 

 troubled about. Thus chloral hydrate was discovered in 1832, 

 but its properties were first recognised through my pharmaco- 

 dynamical researches in 1869. When new alkaloids were dis- 

 covered, the task which lay before the chemist was to test their 

 action upon the organism itself on the chance that it might fit 

 in with a similarity in chemical constitution between their new 

 substances and alkaloids. On account, however, of defective 

 application of methods which lay out of their own beaten track, 

 many chemists overlooked the true affinities of these bodies. 

 In support of this may be adduced an example which has 

 hitherto been scarcely ever quoted. Cocaine was discovered in 

 Wohler's laboratory. Its chemical similarity to atropine led to 

 a chemical investigation of its topical action on the eye, and 

 while it was noted that no dilatation of the pupil occurred, its 

 remarkable property as a local anaesthetic was overlooked. 



NO. 1458, VOL. 56] 



Even the chemists found soon enough the exceptional loss of 

 sensibility which cocaine causes when applied to the tongue ; 

 but it was Roller's medical observations and the clinical observ- 

 ations following which first indicated the correct position of 

 cocaine as a drug. 



The first ideas in testing the materials provided by chemistry 

 in such enormous quantities must naturally be directed 

 towards establishing a connection between their chemical 

 constitution and their action. And from this line of thought 

 many considerations naturally result. Before everything, it 

 compels the speedy observation that the chemical division 

 into groups such as alcohols, aldehydes, ketones, &c. , has no 

 bearing upon therapeutical action. Nevertheless, that a con- 

 nection exists between the actions of certain chemical groups is 

 not to be denied. It has been proved that the great group of 

 bodies allied to antipyrin ("pyrazolones") exhibit similar 

 therapeutic properties in a given direction. But we must 

 always keep in mind that when we wish to speak of the connec- 

 tion between constitution and action, we must recognise that the 

 effect of medicinal action upon the animal and human frame 

 forms a complex whole, and cannot be mapped out with mathe- 

 matical clearness. Bodies which lower the temperature produce 

 an effect which is compounded of various diff"erent factors. The 

 same is true of the lowering of blood pressure : thus one can- 

 not scientifically represent that the chemical constitution of a 

 given substance will be in relation to its influence on a com- 

 plicated diseased condition such as migraine, or perhaps on 

 the killing of the itch parasite, the destruction of which can 

 be accomplished by the most varied toxic agencies. This 

 imperfection of the new method must be admitted, but from 

 its incompleteness no one can deduce that it is useless. On the 

 contrary, its perfection promises to bring forward new and 

 unexpected results. 



But it must also be admitted that if the knowledge of the 

 chemical material be made the basis of research and merely 

 taken by way of comparison in relation to the remedies 

 already guaranteed by experience, this alone already affords 

 sufficient ground for rendering a portion of the chemicals 

 available in treatment. In this connection I may recall, for 

 example, the fact that working from the chemical constitu- 

 tion of cocaine bodies, such as eucaine were obtained which 

 are not, it is true, identical in action with cocaine, but are 

 able to replace it in many cases without exhibiting its toxic 

 action. Thus in the search for new remedies it is no longer 

 indicated that we should wait for chance results, as was 

 formerly the case ; we are, on the other hand, directed by 

 scientific principles. Results crowned with success may be 

 obtained through the most varied combinations which only 

 those ignorant of the scientific method could describe as a 

 "happy chance." 



The Pursuit of Natural Knowledge?- 



After referring to the history of University education in 

 England, and congratulating Sheffield on the union of Firth 

 College and the Medical School to form the new University 

 College, and on its approaching admission as a constituent of 

 the Victoria University, Dr. Pye-Smith said enough probably 

 had been done for the present in constructing the framework 

 for higher education in England. Accumulated endowments 

 were still needful and the working out of the federal type of 

 university. If he might offer advice drawn from the chequered 

 and still uncertain fortunes in London he would say — trust to 

 local wealth and public spirit and avoid Government grants as 

 much as possible. Beware of the utilitarian spirit ; let adequate 

 provision, personal and material, be madp first for literary and 

 scientific research, secondly for educa'ion, and thirdly for 

 technical instruction. The reversed order was the easier, but 

 in the long run he ventured to think the less fruitful. While the 

 moderating influence of statesmen and men of business and the 

 interest and support of past students and graduates would find 

 a valuable place in the constitution, let the chief responsibility 

 rest upon those actually engaged in teaching and research. 



Dr. Pye-Smith then went on to speak of the two senses of the 

 word knowledge, both of them the objects of attainment by 

 students of a university. The desire for knowledge how to do 

 something is historically the earlier and is shared to some 

 extent by the lower animals. Its end was : subjectively, the 

 partly physical, partly intellectual pleasure of exercising the 



1 Abstract of part of an address delivered at the University College 

 Sheffield, by Dr. Pie-Smith, F.R.S. 



