602 



NA TURE 



[October 22, 1896 



]X)ssessing nii power in itself of synthetic construction. It is 

 true that the possible synthesis of organic compounds special to 

 the animal body had long before, in 1828, been shown by 

 Wohler's artificial formation of urea. It is true also that Huber, 

 in the case of bees, and Liebig, in the case of cows, had already 

 shown that wax and fat must be in part manufactured out of 

 something that was not fat. The conclusions, however, of these 

 observers were at best somewhat distant inferences from statist- 

 ical data ; and, in any case, had not as yet made much way in the 

 direction of general acceptance. But Bernard's experiment was 

 in the form of an ocular demonstration. The glycogen which 

 had been formed in the liver could be extracted, could be seen, 

 handled, and, if need be, tasted, a result adequate to convince 

 even a physiological Thomas. We may claim for Bernard's gly- 

 cogen discovery that as the first realistic proof of the synthetic 

 powers of the animal organism it did much to establish a truth, 

 which succeeding observations have only served to confirm and 

 extend, namely, that the animal, no less than the vegetable 

 organism, possesses synthetic powers, and that the want of 

 prominence of these in the ordinary work of the animal body is 

 to be attributed to economic reasons, and not to absence, or even 

 scantiness of power. 



But there is another aspect from which the discovery must be 

 viewed. 



At the time of which we are speaking, physiologists were still, 

 as they had been of old, largely under the influence of a some- 

 what mechanical conception of the body as a collection of organs, 

 each of which had its special use or function, the unity of the 

 Ixidy being maintained by the mutual adaptation of the con- 

 .stituent organs. This was further developed into the view that 

 when a use of an organ had been satisfactorily made out, when 

 a function had been made clear, all that remained to be done, 

 in the way of research, was simply to inquire how far and in 

 what ways the performance of that function was influenced by 

 changes in the rest of the body, or by external circumstances. 

 It was acknowledged, for instance, on all hands that the 

 function of the liver was to secrete bile, and jihysiologists in 

 general were content to look forward for future discoveries 

 which should throw light on the exact nature of the mechanism 

 of the secretion, and on why the liver secreted now more, now 

 less bile, and to these alone without expecting anything else. 



Bernard's discovery that the liver not only secreted bile, but 

 manufactured glycogen, fell on physiologists like a bolt from 

 the blue. The knowledge that the same hepatic cell was 

 engaged both in secreting bile and manufacturing glycogen, and 

 that the sugar or other products of digestion were carried from 

 the intestine, not straight to the tissues which they were destined, 

 in any case, ultimately to nourish, but to the liver, there to 

 undergo transformation and await some future fate, marked the 

 beginning of a new way of looking at the problems of nutrition. 

 It was recognised that these became less simple, more complex 

 than they had formerly seemed ; but the very complexity gave 

 hope of possible solutions. It was seen that as the blood swept 

 in the blood stream through the several tissues, it might undergo 

 profound changes without any visible outward token, such as 

 that of the appearance of secretion in the duct of a gland, or of 

 the contraction of a muscle, might undergo changes which 

 could only be demonstrated by differences in the composition or 

 properties of the blood as it came to or left this or that tissue. 

 The technical difficulties of the analysis of blood prevented any 

 immediate marked steps in the way of advance, and attem]5ts to 

 establish, in respect to any particular tissue, the changes which 

 the blood underwent in it, by inference from the results of 

 experimental interference, met with difficulties of another but 

 no less serious kind. Mence the world had to wait some 

 little time before the new idea which Bernard's discovery 

 had started bore important or striking fruit. Yet it was 

 not very long before it was seen that the hepatic cell had 

 heavy <iuties touching the metabolic changes of ]3roteid, as 

 well as a carbohydrate material ; that it, and not the kidney 

 alone, had to do with urea as well as sugar, and the diffi- 

 culties, which physiologists in the early halt of this century 

 must have keenly felt, how to reconcile the bald task 

 of secreting bile, which alone technical physiology allotted 

 to the liver, with the overweening importance which not only 

 popular experience, but more exact clinical study, could not but 

 attach to that organ, began to steal away. A little later on, 

 exact experimental inquiry converted into certainty the sus- 

 picions which clinical study had raised, that the blood in 

 streaming through the thyroid gland underwent changes of 



NO. 1408, VOL. 54] 



supreme importance to the nutrition of the tissues of the body 

 at large. .Still, a little later, the Bernardian idea, if I may so 

 venture to call it, doubling, so to speak, on itself, led to the 

 discovery that the mysteries of the fate of sugar in the body 

 were not lodged in the liver alone, but might be traced to the 

 pancreas. It was seen that as the blood streaming through the 

 liver worked on sugar, besides secreting bile, so the |>ancreas, 

 besides secreting its marvellous omnipotent juice, also influenced, 

 though in a different way, the career of sugar in the body, that 

 the disease we call diabetes was or might be in some way con- 

 nected with the pancreas no less than with the liver. I need 

 not go on to speak of recent researches on the supra-renal 

 capsules or of other organs. It is enough to note that one of 

 the most promising lines of inquiry at the present day is that 

 relating to the changes of which I am speaking, .sometimes known 

 under the name of " internal secretion." Every year, nay, 

 almost every month, lirings up some new light as to the details 

 of the great chemical fight which the blood is carrying on in all 

 the tissues of the body — it may be perhaps to-morrow that we 

 shall learn of some work of a kind wholly unexpected which is 

 carried out by that great Malpighian layer of the skin which 

 wraps round our whole frame. In any case, the line of inquiry 

 is one of the most fruitful of those of the present day. I may 

 add too, I think, that it is one which has been of the greatest 

 direct use to mankind, and promises still more. It is true that 

 Bernard's discovery of glycogen, and perhaps especially the 

 diabetic puncture, raised hopes which have not been fulfilled. 

 Not to-day, any more than forty years ago, it is in our power 

 wholly to remove the disease which we call diabetes. But short 

 of complete mastery, how great is our pow er now compared with 

 then. And when we remember that the pancreatic relations of 

 sugar are far from being worked out, and that such knowledge 

 as physiologists already possess has not yet made much way in 

 clinical study, we may look forward to marked progress i>ossibly 

 in no very distant time. 



Further, if there be any truth in what I have insisted upon — 

 that the value of a discovery is to be measured not only by its 

 immediate application, theoretical and practical, but also by the 

 worth of the idea which it embodies and to which it gives life ; 

 and if it be true, as I have suggested, that by the genesis of 

 ideas the discovery of glycogen is mother of all our knowledge 

 of internal secretion, in its widest sense, of the work of the 

 thyroid and other like bodies, then the good to suffering man- 

 kind which may be laid to the door of Bernard's initial ex]ieriment 

 is great indeed. 



The next result to which I will call your attention is again an 

 experiment, and once more an experiment on a living animal. 

 In 1850, Augustus Waller described, in the Philosophical Trans- 

 actions, the histological changes which division of the hypo- 

 glossal and glosso-pharyngeal nerves in the frog produced in the 

 fibres of the distal portions of the nerves, and shortly afterwards 

 developed this initial result into the more general view of the 

 dependence of the nutrition of a nerve-fibre on its continuity 

 with a cell in the central nervous system, or in the case of 

 afferent fibres, in the ganglion of the posterior root. 



This discovery was at the time, and has since continued to 

 be of value as a contribution to physiological ideas: it had its 

 share in promoting the progress which, though shght, is still a 

 progress, of our understanding the obscure influences which the 

 part of a cell enclosing the mysterious nucleus exercises over all 

 the rest of the cell. And perhaps even to-day the theoretical 

 value of that degeneration of nerve-fibres, the knowledge of 

 which we owe to Waller, is not adequately appreciated, and 

 the lead which it gives not followed out as it might be. In 

 spite of all we know, we are too much apt to fall back on the 

 conception that, when no nervous impulse is travelling along a 

 nerve-fibre, the nerve-fibre is in a state of motionless quiescence, 

 and that a nervous impulse, when it does come, sweeps over the 

 fibre as a wave sweeps over a placid lake. But the Wallerian 

 degeneration gives such a view the lie direct. When we reflect 

 that the finely-bakinced molecular condition, which itself i.s 

 nothing more than the falsely seeming quiescence of an equili- 

 brium of opposing motions, in the ultimate fibrils of the nerve- 

 twigs, in the ultimate phalanx of the finger, by which we touch 

 and get to know the world without us, is dependent on what is 

 going on around the nucleus of a cell, or the nuclei of some 

 cells in the ganglion or ganglia of certain upper spinal nerves, 

 so that if the continuity of the .axis cylinder process be any- 

 where broken, the figure of the molecular dance changes at 

 once, and riot takes the place of order. When we reflect on 



