412 



NATURE 



[August 24, 1882 



pends upon the activity of its individual units, the gland cells ; 

 and these units may discharge their function so long as they con- 

 tinue to live and are supplied with the nutriment — mineral, 

 organic, and gaseous, which they require. 



Leaving aside, at least for the present, any reference to the 

 arguments which may he derived, hy analogy, from a study of 

 cell life in general, I would call your attention to the physio- 

 1 )gical facts which prove the truth of the proposition ju-t enun- 

 ciated. The first of these facts was discovered by Claude 

 Bernard ; to wit, that when all the nerves supplying the salivary 

 glands are divided, there is at first a temporary cessation of 

 secretion, soon followed, however, by an abundant flow of very 

 wa'ery, so-called paralytic saliva. 



This result is fully confirmed by similar observations made in 

 the case of other secreting organs, and which establish very fully 

 the greater or less independence of the secreting elements from 

 the control of the nervous system; though unquestionably, in 

 a normal state of the organism of higher animal*, the nervous 

 system is continually intervening, both directly by its influence 

 on gland cells, and indirectly by the changes which it produces 

 in the circulation, so as to control the operations of gland cells, 

 and especially to bring them into relation with, and subordinate 

 them to, the work of complex processes of the organism. 



What the exact relations of nerve fibres to gland cells may be 

 is yet a matter involved in great doubt. The discovery made by 

 Pfliiger of the terminations of nerve fibres in the secreting cells 

 of the salivary glands has not been confirmed by any observers 

 in any vertebrate. Kupffer has, however, unquestionably done 

 so in the case of Blalta cricntalis, and although as yet objective 

 proof is wanting, we cannot entertain any reasonable doubts 

 that a connection between the ultimate fibrilla? of nerves and 

 secreting cells actually exists. We feel confident that physical, 

 as it were accidental, difficulties have alone hindered the precise 

 determination of the fact. 



The Immediate Source of the Nutriment consumed 

 by the Gland Cell. 

 In the original scheme of a secreting gland, developed first of 

 all by Bowman, then adopted byGoodsir, Carpenter, 1 and many 

 other writers, the essential structural elements taken into account 

 were the following: — I. Epithelial cells lining the secreting 

 cavity of the gland ; 2. Sub-epithelial tissue, usually presenting 

 superficially the form of a basement membrane, upon which the 

 cells were placed ; and 3. A capillary network in closer relation 

 to the basement membrane, or more superficial part of the sub- 

 epithelial tissue. In harmony with this scheme, the glandular 

 elements were always spoken of as drawing their supply from 

 the blood in the capillaries. The one element which was wanting 

 in that scheme, and which we are able to fit into it, thanks again 

 to the labours of the great physiologist of Leipzig, is the relation 

 of so-called lymph spaces to the other elements. As was first 

 shown by Ihe researches of Ludwig and his school, amongst the 

 modes of origin of the peripheral lymphatics, the most numerous 

 are to be found in connective tissue, and nowhere more abun- 

 dantly than in the connective tissue of glands, which is 

 everywhere interpenetrated by irregular spaces containing 

 lymph, from whence spring the minutest lymphatics. If we 

 c msider, then, the immediate environment of the secreting cell, 

 we find that in close proximity to it is the lymph, which is a 

 transudation from the blood, and upon which the gland cells are 

 directly dependent for all the matters which they require For 

 a certain time, then, the gland cell will be independent of the 

 supply of blood, that is, so long as the lymph surrounding it con- 

 tains a sufficient quantity of essential matters, of which oxygen is 

 one of the chief, to support its life, or until it becomes so charged 

 with waste products derived from cell life, e.g. CO a , as to inter- 

 fere with the functions of the latter. It certainly appears that, 

 at least in the majority of cases, it is the secreting cell which 

 modifies, in the first instance, the composition of the lymph 

 which bathes the tissues in proximity to it, rather than the com- 

 position of the lymph wdiich modifies the activity of the gland 

 cell. There are some cases nevertheles; in which it would 

 appear that the presence of certain constituents in the lymph is 

 the direct cause of the activity or increased activity of the cells. 

 Secretino Cells present different Appearances, cor- 

 responding to different States of Functional 

 Activity. The Researches of Heidenhain. 

 Amongst the physiologists of Europe who have most enriched 

 ' Carpenter in his admirable article on "Secretion" in "Todd's 

 Cyclopaedia of Anatomy and Physiology." 



science by their researches during the last thirty years is unques- 

 tionably Professor Heidenhain of Breslau, who has exhibited his 

 mastery of the physical side of physiology by his classical re- 

 search on the relations between the heat evolved in and the work 

 done by muscle, and as a biologist able to use in the best manner 

 all the resources of modern histology in the elucidation of bodily 

 function, by the researches to which I wish to direct your 

 attention for a few moments. 



The glands imbedded in, or the ducts of which open upon the 

 surface of the mucous membrane of, the alimentary canal, for 

 the most part, are characterised by periods of more or less com- 

 plete cessation of activity, as judged by the diminution, or 

 absolute cessation, of the secretion which they prepare. This 

 is true of the salivary glands and of the liver, but particularly 

 true of the gastric glands and the pancreas. 



Certain of these glands, i.e. the salivary glands in some 

 animals, and the stomach and pancreas in all in which they 

 exist, have the task of preparing juices which contain certain so- 

 called unformed or unorganised ferments or enzymes, upon 

 which the properties of the secretions in great measure depend. 

 Heidenhain in a long series of investigations, which have been 

 taken part in by certain other scientific men, as by Ebstein and 

 Griitzner, by Kiihne and Lea, and particularly by Mr. Langley 

 of Trinity College, Cambridge, has shown that the secreting 

 cells of a particular gland, as for instance of the submaxillary 

 gland, of the gastric glands, and of the pancreas, exhibit 

 diff -rences in size, differences in the form and appearance of the 

 nucleus, and differences in the cell contents, corresponding to 

 varied states of functional activity. 



Time will not permit my mentioning in detail the results of 

 the-e observations from which, however, certain general con- 

 clusions appear derivable. Thus, a gland cell at rest is usually 

 larger than a similar cell which has been engaged in the process 

 of secretion ; from its behaviour to reagents, it usually appears 

 to contain within itself an abundant store of the body or bodies 

 which are chiefly characteristic of the secretion, or closely related 

 antecedents of these, and the amount of undifferentiated pr ito- 

 plasm surrounding the nucleus appears to be at a minimum. On 

 the other hand, the gland cells, which have been secreting for a 

 greater or less period, often, though not invariably, present a 

 diminution in their size, a diminution in the amount of the 

 characteristic bodies previously referred to, and an increase in 

 the protoplasmic constituents of the cell. All facts, histological 

 as well as physiological, seem to point to the following con- 

 clusion : that during rest, the cell forms, at the expense of, or as 

 the product of the differentiation of, the cell protoplasm, the 

 bodies characteristic of the secretion ; that whilst secretion is 

 going on these leave the gland cell ; and that, at the same time, 

 the protoplasmic constituents of the latter increase at the expense 

 of the lymph, to be converted secondarily, either at a later period 

 in that particular act of secretion, or in the succeeding period of 

 inactivity, into specific constituents. The researches of Heiden- 

 hain have been conducted upon the glands after these had under- 

 gone processes of hardening and straining, the appearances 

 observed indicating changes which, though not identical with, 

 at least corresponded to various conditions of the gland. Kiihne 

 and Lea and Langley have, however, studied glands in a living 

 condition, and though the appearances were not identical with 

 those observed by Heidenhain, they entirely confirm these. 



I have not time to do more than refer to the fact that in some 

 at least, though probably in all of the cells of glands which pro- 

 duce secretions containing ferments, there are formed at first 

 bodies to which the generic term of "zymogens " may be applied, 

 i.e. ferment generators, from which a ferment is afterwards set 

 free. 



In connection with this part of my subject I may refer to the 

 view, which was at one time held by some, that in secreting 

 glands the gland cell having produced the matter of the sec-etion 

 was thrown off, discharging its contents into the secretion. This 

 process, when it does occur, must be looked upon as exceptional, 

 and as it were accidental. 



Amongst the most striking examples ol the success with which 

 physiological experiment and subsequent histological research 

 have been pursued in combination so as to throw light upon the 

 functions of particular cells, I may refer first to the observations 

 of Heidenhain, secondly to those of Nussbaum on the excretion 

 of colouring matters, artificially introduced into the blood, by 

 the secreting epithelium cells of the renal tubules. I have 

 previously referred to the theory of Bowman, according to which 

 the watery and saline constituents of the renal secretion were 



