e^'«^'^ ^^1^^. "^tM; '^^■ Ci* HI '«< ^ '^^ CORNELL UNIVERSITY LIBRARY Cornell University Library QH 581.B96 Cell: 3 1924 024 756 672 The original of this bool< is in the Cornell University Library. There are no known copyright restrictions in the United States on the use of the text. http://www.archive.org/details/cu31924024756672 PRIZE^E^S S A Y. THE CELL: PHYSIOLOGY, PATHOLOGY, MJ) PHILOSOPHY; AS DEDUCED FKOM ORIGINAL INVESTIGATIONS. TO WHICH IS ADDED ITS HISTORY AND CllITICISM, BY WALDOS. BURNETT, M.D., or BOSTON. ITatura in minimis maxima est. INTRODUCTORY NOTE. This Essay was written in the latter part of 1851, and the many advances the science of structure has since made, has thrown so much light on some obscure poiifts, that the parts relating to these ought almost to be rewritten, to be up with the times. I have sought to, at least in part, make good this deficiency, by inserting as much new matter as well could be, while the sheets were going through the press. Boston, Sept. 1853. PREFACE. Physiological Science has such extended relations, and occupies so wide a field, that any one of its departments alone, furnishes us ■with material sufficient for the study of our whole lives. Each one of its specialities now covers more ground than did the entire fabric as understood by the earlier writers. This is so true that any comprehensive treatise on Physiology written at the present time would be encyclopsedial in size ; and, if the labour of a single indi- vidual, would necessarily be quite imperfect. These views being correct, the plan of the present work, as indi- cated by its title, may seem altogether too comprehensive, if not presuming. But a consideration of the whole matter has led me to think that no other plan could be pursued that would enable me so well to advance those ideas and doctrines which experimental inquiry has shown me to be true. Our most rational Pathology must now be considered as based upon our clearest and most correct ideas of physiological action. In fact, Pathology cannot, like Physiology, be regarded as a distinct science ; for it is but the erring condition of the latter — its actions modified and governed by the same laws, but acting upon different premises. These two branches, then, are efficient mutual aids. There can be no correct understanding of pathological phenomena without a pre- vious knowledge of physiology; and, on the other hand, no one can carefully study the former without having his ideas of the latter made more clear and comprehensive. It was for these reasons that I did not take for my subject, sim- ply the physiology of cells, which would alone have been sufficiently extensive. It may not be amiss for me to state that all the statements, facts, illustrations, &c. contained in the essay are my own, when not other- 648 PKEFACB, •wise indicated ; moreover, most of them were prepared and made spe- cially for this work. It has been a source of regret that so few of the more recent German works have been accessible to me in the preparation of this subject. During the past few years especially, the number of mi- croscopical observers in Germany has been very great, and there are a corresponding number of works being published, of the highest and most trustworthy character. It would indeed be well if Ameri- can students would divert somewhat their attention from Paris in this direction. Most noted among these is the masterly work of Kblliker [Mihro- scop. Anatomie, ^c), of which I unfortunately was able to possess only a small part until after the completion of this essay. INTRODUCTORY CHAPTER. HISTORY AND CRITICISM OF CELL-DOCTRINES. A SURVEY of the rise and progress of any of the inductive sciences fully shows that signal discoveries are never due to the labours of a single individual. For there existed previously, minds that had rudely caught at the same idea, or imperfectly pursued the same line of inquiry ; but in which, either from want of requisite data, or more generally from the absence of a peculiar mental capacity, the subject did not reach its full maturity. Subsequently, however, that indi- vidual becomes the discoverer, who is so gifted that he can apprehend that peculiar colligation of facts, which always must and always does precede the discovery of an important scientific law. This view of the relation of the Discoverer to the discovery, detracts no merit from the former, for the work, however nearly finished it might have been, would not have been completed, had not the discoverer set the seal of his capacity upon it. The history of the inductive sciences is full of examples bearing directly upon this point. In physics, such was true of the law of gravitation, as brought out in a perfect form by Newton. Every one had witnessed the falling of bodies towards each other or the earth ; but it needed the mind of Newton to perceive in it the expression of a law as wide as nature herself. Without alluding to other instances, I may say that this view is fully sustained by the historical relations of the subject under con- sideration. As we shall soon see, the existence of Cells, as compo- nent parts of the organisms, had long been known to anatomists and physiologists, but this fact found, for 'the first time, in the mind of Thos. Schwann, the requisite capacity to perceive in it the funda- mental expression of organization, and that, therefore, it must have an application as wide as the range of organized beings. This principle of discovery, as it may be called, the gift of a for- tunate few, appears to sustain relations to physical facts, either singly or collectively, other than those with which we are now con- VOL. VI. — 42 650 THE cell: versant. So that I can entertain no doubt but that the truth of the whole law was impressed upon the mind of Schwann just as forcibly at the hour of its suggestion, as it now is, after its widely extended verification. The task of tracing out historically those steps of progress in physiology, which necessarily preceded the advent of the modern cell-doctrines, cannot be otherwise than both pleasant and profitable. There is a difficulty, however, in reducing it to the limits of a single chapter, without making that chapter include several others which treat of particular cells ; and, therefore, to avoid repetition, if the following account is incomplete, the remaining portion must be looked for in the following pages, devoted to particular points. The recognition of the fact that vesicles constitute a component part of the animal economy, did not, of course, occur until after the application of magnifying powers to anatomical structures. When this was made, is a point too obscure to be settled. But it appears to me that the application of such powers, in an intelligent way, cannot be traced farther back than the time of Malpighi and Leeuwenhoek, who seem to have observed wonderful things through their rudest of glasses. Malpighi* recognized the blood-corpuscles as little globules, and Leeuwenhoekf has given quite a good description of them, even to some peculiarities of their form. The labours of both these anato- mists, in other departments, were something to the same effect ; they made out tolerably well some structures and caught glimpses of others, but did not advance to the point of conceiving that there was any unity in organization, or that the vesicle was anything but one of its almost ever-varied forms. The observations of Hewson,{ made nearly one hundred years * Malpighi, Opera Posthuma, London, 1686, p. 92. f Leeuwenhoek, Opera omnia seu, Arcana Naturse detecta, Lerden, 1687, torn. ii. p. 421. X Hewson, Experimental Inquiries, London, 1774-77. Vide also Sydenham Society edition of his works. Remarks. — Owing to the much greater ease of study, the structure of the vegetable tissue, as cellular, appears to have been made out at an early date. It seems to hare been first pointed out by Rob. Hooke (Miorographia, London, 1667). But it received a considerable advance from Malpighi, who sent his great work (Anatome Plantarum) to the Royal Society of London, in the year 1670. His observations ap- pear to have been very accurate, and not only did he maintain the cellular structure of plants, but also declared that it was composed of separate cells, which he desig- nated "Utriculi." From this time until the year 1831, the cell (I should say rather vesicular) structure of plants was pretty clearly understood by botanists. See Mirbel, Traite d'Anat. et de Physiol. Veg., Paris, 1802. Also, the earlier works of Hugo Von Mohl. ITS PHYSIOLOGY AND PATHOLOGY. 651 after, although remarkable for their time, and containing many tolerably ■well-elucidated points, involved no histological relations, and in this respect did not perhaps contribute much to the advance of definite ideas of fundamental structure. In fact, during the 17th and 18th centuries, the microscope, rude as it was, existed in the hands of but few, and was, for the most part, used to gratify a youth- ful curiosity, instead of being applied to the elucidation of any intri- cate subject. The labours of Haller should not, in this connection, pass unno- ticed; for, although he may not have elucidated many points by the microscope, yet the doctrines which he advanced, based upon a most profound erudition and an extensive experience, all tended to assign an individuality to organization ; and with such a unity of purpose, there would necessarily supervene a seeking for a unity of structure. It does not appear that any advance was made as to the points under consideration until the time of Treviranus,* who, in 1816, published his account of the tissues, dividing them into three kinds, viz. amorphous, fibrous, and globular. This announcement is somewhat remarkable for its correctness; but I think it must be regarded as premature, the experience of the time not justifying so broad a generalization. The work of Heusinger,t which appeared soon after, may justly be considered as marking an episode in the history of animal tissues. For in it we find views expressed, which, although not founded upon careful and extended investigations, fully show the marked tend- ency of studies of this kind. This tendency here was in the organ- ized, as it had already been in the unorganized world; viz., to seek for the idea of the whole in a unity of elements. Heusinger even attempted to explain how fibres and tubes are formed from elementary spherical globules, by the linear arrange- ments of the latter. J But, remarkable as this may appear, his ideas of these relations if I may thus express myself, seem to have been anatomical, and not physiological; for he does not appear to have conceived of the true physiological signification of these globules. Passing over a brief period, we find that, in 1833, Kobert Brown§ * Tre-riraniis; Vermischte Sokriften, Gottingen, 1816. f Heusinger; System der Histologie, Eisenach, 1822-24. J Heusinger; loc. citat. i. p. 112. g Brown; Transact. Linnean Soc, London, 1833. Although this was puhlished in 1833, there are good reasons for supposing that the discovery should lie dated 1831. 652 THE cell: discovered the nucleus of the vegetable cell, pointed out its constancy, but does not appear to have recognized its physiological relations with the cell itself. Nevertheless, I regard it as a necessary and im- portant step in the gradual development of those doctrines which ultimately were to assume a more perfect form. At about this time a new ardour for the study of minute anatomy seems to have arisen with many German and French physiologists. This was due, in part, to the very admirable class of scientific men just then appearing, and in part, also, to the better class of instru- ments becoming available.* The names of Schultz, Purkinje, Valentin, Wagner, Miiller, and others, cannot be too honourably mentioned for their histological labours at this period. The investigations of Purkinje, in connection with Deutsch,f upon cartilage corpuscles and the process of ossification, served to point out the relations which simple cells might sustain to the more compound tissues. In 1835, there appeared the remarkable work of Valentin,{ upon the histology and development of tissues. I think there can be but little doubt that here we find the first traces of cell-doctrines, or the recognition of cells (I will not say nucleated cells), as the bases of all organized forms ; and which, subsequently, were so brought out by Schwann, that he may be truly said to have made them justly his own. Valentin witnessed the formation of pigment-cells around pre- existing nuclei ; he also instituted the comparison between cartilage cells and those forming vegetable cellular tissue, and pointed out other important relations. § In fact, I think it may be said of Va- lentin, that he perceived the true physiological relations of cells as far as he well could without apprehending the grand fact that the nucleated cell is the fundamental expression of organic forms. It was by the appreciation of this grand fact that Schwann has set his seal upon all previous labours — for this was the vis vitse of the whole matter, and, however strongly Valentin may urge his claimB,|| I can- not regard them in any other light. In the following year Schultz^f published a work on the circulation * I refer here to the instruments of Frauenhofer, Shiek, and Chevalier, f Dentsoh ; De penitiori ossium struotura ohservationes, Breslau, 1834. J Valentin ; Handbuch der Entwickelungsgesohichte des Meuohen, Berlin, 1836. § Valentin; loc. citai., pp. 194, 209, 287. II See Wagner's Lehrbuch der Physiologie, Leipzig, 1839. Tf Schultz ; Das System der Circulation in seiner Eutmokelung duroh die Thierreihe, Stuttgard, 1836. ITS PHTSIOLOST AND PATHOLOGY. 653 of blood, includiEg the histological condition of its elements. He ap- pears to have comprehended the cell relations of the blood particles, and describes their formation around a pre-existing nucleus. He no- ticed also many other important points ; but his results were not appreciated at the time, and no general signification of these phe- nomena was entertained. Immediately suicceeding this, there appeared many new works on microscopic subjects. The microscope had ceased, with scientific men, to be an instrument of curiosity, and was now used as an aux- iliary for the elucidation of the higher phenomena of life. Numerous works were published — among the more prominent of which may be mentioned, those of Henle,* Voge],t Valentin,^ Donnd,§ Boehm,|| and many others, whose articles are scattered through the various journals of the day. This brings us up to the period when Schwann commenced his in- vestigations, upon animal tissues, and with which those of Schleiden upon vegetable structures were opportunely contemporary. The above-mentioned work of Henle fully demonstrated that ani- mal tissues may be nourished without vessels — in fact, having a mode of life like that of vegetables. This, as Schwann himself observes, was a very important advance, as it brought the physiological rela- tions of the two kingdoms to the same point. He showed that the Bete Malpighi consisted of nucleated cells, which grew from smaller ones ; thus establishing the fact of the individual power of cells for their own life and increase. It was about this time that Valentin, f when describing the nucleus of the epidermal cells, remarks, that they remind him of the nucleus that occurs in the cells of vegetable tissues. Still, all these comparisons must be regarded only in the light of analogy instead of homology ; perhaps in the same way that the wings of a butterfly would be compared with those of a bird ; — no fundamental unity was perceived. * Henle ; Symbols ad anatomium villorum intestinalium imprimis eorum epithelii et yasoram laoteorum, Berlin, 1837. I Vogel ; Physiologisch-pathologiBohe untersuchungen ueber Eiter, Eriangen, 1838. J Valentin ; Eepertorium, Bds. i. and ii. ^ Donn4 ; Keoherclies miorosoopiques sur la nature des mueus et de la matifere dea ecoulements, Paris, 1837. II Boehm ; Die kranke Darmchleimhaut in der asiatischer Cholera mikroskopisoh untersuchte, Berlin, 1838. ^ Valentin ; Nov. Act., N. C. xviii. pt. i. p. 96. 654 THE cell: In 1838, the excellent researches of Schleiden* upon phytogenesis ■were published. In it, Schleiden pointed out in a clear and definite way the formation of cells in vegetable structures, according to a single and uniform method; and by him, the law of unity of develop- ment of vegetable cells was believed and advocated. At this time, while Schwann was at work upon the animal tissues, Schleiden communicated to him the results of his investigations, and Schwann, aware of what had been done as to animal-cell formation by Valentin and Schultz, seized upon the grand idea of unity of plan in the appearance of the elementary forms of organized struc- tures. He gave an individuality, a vitality, to the anatomical details then collected. He caught the first glimpses of a truth, which, although it then needed a verification, was soon to be recognized as the grandest in physiological science. The correct apprehension, then, of this law of fundamental devel- opment, as applicable to all organic structures, belongs to Schwann.* The steps of progress preceding it we have just reviewed. It is evi- dent that the same course of inquiry had been imperfectly pursued before, or even that, previously, the same idea had been rudely grasped. In fact, according to the very constitution of science, it could not have been otherwise ; for its history has taught us that in- duction is its broad highway, and it would be equivalent to conferring divinity upon a man to state that he made a grand discovery in science which had no relations whatever with the labours of others who had preceded him. Such appears to me to be, in brief, the correct view of the origin and complete development of the cell-doctrine. I have based it upon all the historical evidence within my reach. It now remains to take a survey of the subject since that time ; or, rather, since it attained its individuality of expression. If it is true that all in physiology appertaining to animal cells, up to the time of Schwann, was truly made his own, by the inter- pretation he passed upon them ; the same is nearly equally true of the labours in this department, made during the three or four years succeeding the publication of his work. For, those who took up this * Schleiden; Beitriige zur Phytogenesis. Miiller's Arcliiv, 1838, pt. ii. It appears, however, that these inTestigations were made some time before this date, for Schwann mentions that Schleiden communicated them to him in October 1837. Vide Mikroskop. Untersuch., (preface.) t Schwann ; Mikroskopische Untersuchungen ueber die Uebereinstimmung in der Struotur und dem Waohsthum der Thiere and Pflanzen, Berlin, 1839. ITS PHYSIOLOGY AND PATHOLOGY. 655 line of investigation, and wlio, in one sense, deserved the name of original observers (when they recorded their own observations, pre- ferred to quote the original language of Schwann). This is a fact in the history of science well worthy of remembrance, and especially by those who seek the honours due to the correct study of natural phenomena. In the verification of this grand idea, the wide range over which Schwann extended his labours, has truly made subsequent observers feel that that field had been almost entirely preoccupied. It has also impressed upon them the belief that so much labour could only thus be so successfully accomplished, except under that scientific conviction of fundamental unities in nature; a teleological instead of a physical view of the relations of natural phenomena ; which has always been the guiding spirit to great success in the comprehension of nature.* But, in thus expressing myself, I would not claim too much for Schwann. Signal advances in any science require the successive and accumulated labours of many worthy men. In the present case, if, on the one hand, subsequent and more extended researches showed that the generalizations, naturally adopted by Schwann, were too broad, yet, on the other hand, this field has since been extended in a hitherto unknown direction. The doctrine of Schwann is, that all animal tissues originate from cells, and that these cells are always formed around a pre-existing nucleus. As to each of these prominent points, differences of opinion have arisen with subsequent observers. That all tissues have not the necessary pre-existence of cells, was advanced first by IIenle,t as to some of the so-called fibrous tissues, and has since been verified as to structures known as JibriUated. In other words, a tissue may be formed by the aggregation of granules in a certain way, and without the intervention of true nucleated cells. As to this point there can now be entertained no doubt, for, since the time of Henle, it has and may be constantly observed. But in regard to the other point, the formation of cells otherwise than around a pre-existing nucleus, the opinions have been many and * I should mention, hoTfever, that, judging from a portion of Schwann's writings, he took the physical instead of the teleological view of organization. See loc. cii. Syd. Soc. Ed. p. 187. t Henle ; Traite d'Anatomie g^n&ale. Trad. d'AUemand, par A. J. Jourdain, 2 vol. Paris, 1843, tom. i. p. 374. 656 THE cell: various. Among the first who expressed their dissent, was Reichert,* who, in his embryological studies, sought in vain for the constant pre- sence of the nucleus in the vitelline cells. The discovery of Ascherson,f as to the phenomena sequent upon the conference of oil and albumen, was of some importance in rela- tion to this point. For, according to it, cell-membranes might be formed around a drop or minute particle of oil, and without any nu- cleus. But this doctrine did not have much weight at the time, and we shall see, hereafter, that a different interpretation should be put upon these phenomena than had been supposed. The phenomena of the multiplication of cells by segmentation, presented new and irreconcilable difficulties. The subject did not seem at all clear upon any explanation ; moreover, at this time, HenleJ had observed appearances connected with cells, which, al- though he was inclined to adopt generally the view of Schwann, led him to express his dissent of its universality of application. At this time, the writings of Hugo Von Mohl§ and Nageli,|| as to the formation of vegetable cells, supported the doctrines of Schleiden and Schwann ; and, considering their authority, tended, no doubt, to confirm the old view. The immediately subsequent writings, however, of physiologists of both the vegetable and the animal kingdom, were of a different character. In 1843, Karsten^f published his disserta- tion on the cell, in which he dissented entirely from the " standard view," believing that cells originate without a pre-existing nucleus, -and by the expansion of amorphous granules of organic matter. In 1844, Kolliker,** a most trustworthy observer,after a considera- tion of the whole matter, expresses his belief in the want of unity of mode of cell formation ; and declares that, if there is a single method which is invariable, it yet remains to be discovered. This was also the opinion of most of the excellent observers of the time. In fact, the method of Schwann seemed to be admitted as that of the excep- tion rather than of the rule. Although such discrepancies in science are unpleasant at the time, yet, by them, science makes its most signal advances. In the present case, it was now evident that there * Eeiohert; Das EntwickelimgBlebeu im Wirbelthierreioh, Berlin, 1840, pp. 6, 93. f Aecherson ; Miiller's Archiv, 1840, p. 49. X Henle; Lelire von den Gewebe, Leipzig, 1841, p. 154. I MoU ; Vermischte Schriften, p. 84. II Nageli; Ueber Entwiolielung des PoUens, Zurich, 1842. 1[ Karsten; De Cella vitale Dissertatio, Berlin, 1843. ** Kolliker ; EntwiokelungsgeBohichte der Cephalopoden, Zurich, 1844. ITS PHYSIOLOGY AND PATHOLOGY. 657 was much to learn about a point which had been long regarded as quite definitely settled. I shall not here dwell upon the details of these different views, for they are not easily understood without the aid of figures. But it appears pretty evident, and has since been so verified, that they were based upon correct observations. These differences seemed to in- crease in exact ratio with those of the observers. In 1846, Mr. Paget,* in his excellent Report on the Progress of Anatomy and Physiology, expressed his doubts of the sufiiciency of the then existing theories to explain many phenomena observed in the study of morbid growths. He had seen large growing tumours, in which there was not a nucleated cell, being only a collection of fibres ; on the other hand, he had met with those, being only a mere collection of cells, and never apparently passing beyond that stage. This led him to the opinion that, in morbid growths at least, the cell is sometimes to be regarded as the terminal and not the transitional form. How far these views may be regarded as correct will be discussed on a future page. Corresponding views, that soon followed from a great number of observers and writers, need not detain our analysis here.f More- over, their writings are scattered through a mass of literature ; and, even were any criticism desirable, it could be made with difficulty. Since 1846, up to the present day (1851), the clearest and proba- bly the most correct views of the origin and nature of cells, whatever may have been the mode, have been derived from the careful study of the genesis and structure of morbid growths ; which, because they are morbid, are infra-formations, yet are connected with healthy tissue, and therefore may be justly considered as most fit for these inquiries, * Paget. Report on the Progress of Anatomy and Physiology. July No. British and Foreign Medical Keview, 1846. •j- Among the writings that have appeared -within the past few years, the following may be mentioned as worthy of reference : — Reichert ; Miiller's Arohiy, 1844-53. — The relations of cells, and the progress of the science, are here thoroughly discussed. KoUiker; Schleiden's and Nageli's Zeitschrift, fur Wiss. Botanik, 1845, heft ii. — This is a lucid exposition of the origin and nature of the nucleated ceU. Reichert; Miiller's Aiohiv, heft ii. and iii. 1846. — Meckel; Miiller's Archiy, heft i. 1846. — Courtz; Gaz. Med. de Paris, 18 Avril, 1846. — Harting; Botanische Zei- tung, 1846, p. 46.— Hugo Von Mohl; Botanische Zeitung, 1846, p. 387.— Nageli; Schleiden's and Nageli's Zeitschrift, fur Wiss. Botanik, heft iii. and It. 1846 ; see also the translation by the Royal Society. Gairdner ; Rep. Brit. Assoc. Ad. So. 1850. — For other references, see the Tarious English, French, and German Physiological text-books of the last four or five years. 658 THE cell: PART I. PHYSIOLOGY OF CELLS. CHAPTER I. GENERAL RELATIONS OF CELLS TO ORGANIZATION. When a fact in nature has once been fully recognized, we are apt to seek for it too broad an application and generalization. This may- be due to a fundamental law of human reason — an instinctive tend- ency to unity in our knowledge of all natural phenomena ; it is a kind of intuitive prevision, which is really founded on induction in part, but of the use of which in science we cannot be too careful. Schwann was led to make this application in regard to the histology of all animal tissues ; and, although subsequent experience has shown that it is not true as to the exact manner in which it was enforced — that is, the nucleated cell as the necessary basis of all tissues — yet it holds true when considered as to the real philosophy of cell life. As we have mentioned in the history and criticism, there is a class of structures the formation of which does not involve nucleated cells. Such are fihrillated and granular tissues, both as healthy and diseased products. They are formed by the aggregation and conference in a- regular way, of the primordial granules of organizable liquids. All the other tissues, whatever their function or aspect, are formed through the agency of nucleated cells. In fact, these cells appear to be a physical state, through which, in order to acquire functional organization, these tissues must pass. In many of the compound tissues of the higher animals, the phases of these transformations are not easily traced, for they are transient, and generally not well de- fined. But, in some of the lower forms of animal life, and especially those which are aquatic, this is not the case, for here the adult forms are in one sense the persistent representatives of the embryonic forms ITS PHYSIOLOGY AND PATHOLOGY. 659 of tte higher types. On these accounts, our clearest views of the nature and function of tissues, have, in almost every case, been due to studies upon inferior animals. In the following pages, the advan- tages thence accruing will be easily perceived. Upon a compre- hensive and correct appreciation of the relations of these various phases of cell-transformation, is based all our real fundamental know- ledge of physiology. There is one point concerning all these cell-conditions and trans- formations, which is now pretty well determined. It is that, in those cases in which the individuality of the cell is swallowed up in the substance of a tissue, the tissues thus formed are subservient to the functions of organic life. On the other hand, in those cases in which the individuality of the cell is preserved, so that a single cell is a true histological representative of the whole tissue, the tissues thus composed perform the higher functions of the economy, such as secretion and the elimination of certain forces. The idea here in- tended to be conveyed will be perceived, if I mention the schlerous and muscular tissues as examples of the former, and the nervous and epithelial tissues as examples of the latter case. This statement is, I believe, quite true with all except the lowest forms of animal life. The relations of cell-studies to organization as modifying our ideas of the nature, de ipso, of function when applicable to animal tissues, require here a brief mention. Our ideas of the peculiarity of the function of any tissue are based upon our experience with it as such. Thus, we have been so accustomed to associate animal motion with the muscular tissue, that the former is not easily conceived possible without the presence of the latter. And, again, we have been so wont to link sensation with the nervous system, that the presence of the former has been deemed impossible without that of the latter. But cell-studies, in the lowest forms of animal life, show that these views are incorrect ; for with them we do have motion without muscle, and sensation without nervous tissue ; and in each of these cases, as we shall more fully show hereafter, the results are due to the agency of simple cells. In these facts, which have been carefully made out, is embodied a great deal of physiological truth ; for we are thereby taught that function cannot be regarded as the result of this or that material form, but that this form exists as such in virtue of the function being performed perfectly. In other words,- it is the acceptance of the teleological instead of the physical view of the relations of physi- ology to anatomy ; a result, which I cannot conceive could have been 660 THE cell: obtained, except by a study of these ulterior forms of organized matter. And, while it is the legitimate offspring of such studies, it is at the same time the almost prophetic guide to many of our safest conclu- sions. > The general relations of cells to organization, as illustrated in the reproductive processes, cannot here be considered without a more extended view of these last than would be compatible with this part of my work. The elimination of a new and distinct being, is, pro- perly, the only true individualizing process of the economy ; for, if I may thus express myself, it is the potentiality of life made mani- fest in a chosen material form. This form is a nueleated cell, which, as it is the form in which and by which life dawned upon the inor- ganic world, so also does it seem the most appropriate form by which all the mutual physiological relations with that world can be best sustained. CHAPTER II. CELL-aENESIS IN GENERAL. A KNOWLEDGE of the anatomical relations of an organized form, has always preceded the correct appreciation of its physiological conditions. This is so, perhaps, because the former are more easily made out, and when well understood scarcely admit of an hypothesis. In cell-studies, as we have already seen, this has been quite true. Many botanists and anatomists, before the time of Schleiden and Schwann, understood very well the anatomical relations of cells. The same is true, also, of cell-genesis ; for, as has been stated, both Valentin and Schultz had accurately observed how it occurred. The first description of cell-formation, as clearly understood from special study, appeared, as is well known, in the paper of Schleiden, pub- lished in 1838. The view here expressed was founded upon studies made upon vegetable structure ; it coincides exactly, however, with the view of Schwann, based upon investigations of animal tissues. The brief but comprehensive description of cell-formation given in their works has been stereotyped in the minds of all subsequent physiologists. The well-formed cell consists of a close membrane or sac, more or less transparent, and filled with liquid giving it a glo- ITS PHYSIOLOGY AND PATHOLOGY. 661 bular aspect. In this contained liquid is situated a small solid (?) body, either floating free or attached to the walls of the cell : this is the nucleus. This nucleus may be also hollow like the original cell- membrane ; and, like it, contains a liquid in which is a smaller solid (?) body called the nucleolus. The cell consists, then, of three parts, and is called nueleolated. But we will take the simple nucleated cell, consisting of only the first two; here the nucleus is the germ of the whole, and therefore must exist before the cell-membrane itself. Moreover, the nucleus is supposed to differ also as to its chemical composition from the remaining parts of the cell. According to Schleiden and Schwann, therefore, the nucleated cell is regarded as consisting of three distinct parts, viz. : cell-membrane, cell-liquid, and nucleus. The nucleus is the starting-point. These nuclei, or cytoblasts, as they have been called, already existing in a formative plasma, the following is the mode by which the complete cell is formed. I take it from Schleiden, as originally published in 1838 : — " So soon as the cytoblasts have attained their full size, a delicate transparent vesicle rises upon their surface. This is the young cell, which, at first, represents a very flat segment of a sphere, the plane side of which is formed by the cytoblast, and the convex side by the young cell, which is placed upon it somewhat like a watch-glass upon a watch The vesicle gradually expands and becomes more consistent, and, with the exception of the cytoblast, which always forms a portion of it, the wall now consists of gelatine. The Fig. 1. The mode of cell-formation, according to Schleiden and Schwann * u. Cytoblasts or nuclei, b. Same, more highly magnified, showing nucleolus, a'. Formation of nuclei, a". More highly magnified, c. For- mation of cell-memhrane from nucleus (6). d. Cell entirely formed; nucleolatedj and nucleus in centre, free. * Vide Sydenh. Soc. edit, of their Researches. 662 THE cell: entire cell then increases beyond the margin of the cytoblast, and quickly becomes so large that the latter, at last, merely appears as a small body inclosed in one of its' side-walls." I have thus quoted this description at length, that the peculiarity of this mode of formation might be clearly seen. It is at once evident, that," if we admit the view here advanced to be correct, the existence of cells always presupposes the existence of nuclei ; the former never being formed without the latter existing previously. In the history of this subject, I have alluded to some of the views dissimilar to the preceding one, which have been urged by observers since the time of Schwann. It appears, however, that they have been less inclined to put for- ward particular views of their own than to assert that they have been unable to witness the phenomena described by Schwann. And some observers,* whose experience in these matters is not incon- siderable, have declared that they have never witnessed the forma- tion of cells in the way above mentioned. My own experience, although not quite so exclusive, has not been much diiferent. I have, in watching the formation of blood-cells, and that of some pathological corpuscles, seen all the phenomena pointed out by Schwann. But I have failed to recognize their uni- versality, or even commonness. On the other hand, the whole tend- ency of my experience generally, and the results I have obtained from quite an extended series of investigations made especially with this object in view, have pretty clearly shown me, that, in animal tissues at least, the usual mode of cell-formation is based upon quite a dif- ferent plan — involving views of the relations of the different parts of the cell to each other which I think pretty well borne out by the results of recent investigations, made by myself and others. I propose to describe this mode somewhat in detail, not only be- cause I think it new, and humbly claim for it an originality, but because of its commonness. f We will take the example of the production of new cells in the * Paget; Report on the Progress of Anatomy and Physiology. — Brit, and For. Med. Ee-view, July, 1846. Also, Gairdner ; Report of the British Association for the Advancement of Science, 1850. f This new mode of cell-formation I presented in a paper to the American Asso- ciation for the Advancement of Science, Camhridge meeting, 1849. See the Proceed- ings, p. 261. ITS PHYSIOLOGY AND PATHOLOGY. 663 adult tissue. An organizable hyaline plasma having been effused by the nutrient vessels ; in this plasma, minute dark points or utricles begin to appear. These constitute the first material manifestations of organization, and, strictly speaking, are the germs of future cells. They are minute sacs and not solid particles ; a point I have very satis- factorily determined by the aid of the highest and best microscopic power. They appear to be fornied by the conference of a minute particle of oil with albumen, uniting under the influence of vitality, according to the so-called Ascherson mode of cell-membrane formation. These minute utricles give the blastematous liquid a dotted aspect ; moreover, being hollow sacs with albuminous walls, they are capable of endosmotic and exosmotic action. By endosmosis they increase, and become clearly visible closed sacs, which increase and grow appa- rently by simple expansion. Having obtained a certain size, the process of the formation of a nucleus begins to take place. This is accomplished in the following manner : The closed sac above de- scribed is filled with liquid; this is clear at first, but soon a cloudiness throughout appears. This nebulous appearance commences to recede from the periphery, where there appears a light space, the central portion of the liquid, however, being all the more dark and opaque. This condensation towards the centre going on, it terminates by the appearance in the centre of a minute vesicle or body, which is the nucleus. It is then a nucleated cell, capable of all the functions of such particles. After such processes have occurred, it may happen that this vesicular nucleus expands, as did the original cell-wall, and then, the same changes taking place, a body is formed within it; and in this way 'there is formed a nucleated cell in a closed cell mem- brane, constituting the true nucleolated cell. But in normally formed tissues, these last-mentioned changes are far from being common ; the original cell-membrane rupturing and passing away before the nucleolus is formed. In brief, the mode of cell-genesis here described consists in the following points : 1st. The appearance of a primordial utricle in a formative blastema. 2d. Its expansion into a clearly seen vesicle. 3d. The partial condensation of its liquid contents towards the cen- tre, giving rise to a new utricle, constituting the nucleus — the whole forming the complete nucleated cell. It will immediately be perceived that, according to this mode, the cell proper necessarily exists before the nucleus, which is a kind of daughter-vesicle formed within it, and is a secondary product — but not at all dissimilar, either genetically or histologically, from the 664 THE cell: cell itself. According to this mode, also, there may be cell-sacs without nuclei, the formation of the latter having never, from some imperfection, taken place ; then again there may be many nuclei in a single cell-sac. Fig. 2. a, o o O h O O o O <,o U ('?,. Cell-formation, as I have observed it. — a. The so-called granules, which are really utricles, being formed by the union of oil and albumen. &. The same, increased in siae by simple expansion, c. Still larger, and liquid contents cloudy, d. Condensation of cloudiness towards centre, leaving periphery clear, t. The same, farther progressed. /. Condensation finished, ending in a clear vesicle — the nucleus — the whole being the rawcZeaied ceZZ. g. Cell with liquid contents cloudy, as in c. h. The same, still farther pro- gressed, as in cZ. i. Condensation finished, ending in a clear vesicle — ^the nucleolus — the whole being the nucleolated cell. This mode of cell-genesis, which may be regarded as a peculiar one, has been based upon the results of a series of investigations made upon the origin and development of epithelial tissues ; and I may also add that all or nearly all of my studies of the intimate character of tissues, both normal and pathological, have tended not only to support, but confirm this view. My investigations upon the vegetable tissues have not been extended, and if from what little I have seen I should be entitled to an opinion, I should say that this mode holds equally valid here, and the phases of development of some of the Cryptogamia appear to have a very good solution with this method of genesis. The difference between the view of Schwann and Schleiden, and this one just enunciated, is this : The former regarded the nucleus as a primary formation, and as histologically and chemically different from the cell itself which is formed around it ; while, according to my own view, on the other hand, the nucleus is a secondary product, formed in the cell-vesicle, and with which it is in every way homo- logous. ITS PHYSIOLOGY AND PAT-HOLOaY. 665 I have found this mode of cell-formation to be quite general, and serving to explain phenomena hitherto obscure. In pathological pro- ducts of either a heteromorphous or homeomorphous nature, it may be clearly observed. In fact, in many of these instances, I have been unable to perceive how any other view could be applicable at all. In the normal textures, and especially those of the lower animals, in which the tissues remain persistent on their cell-stages, the same line of procedure is followed. The phases of genesis which are due to a difference of the cells themselves, cannot be well understood unless we take up their formation, each specially, as it occurs in the animal kingdom. CHAPTER III. CELL-GBNESIS IN PAETICULAE. I. The Ovum. As is now well known, the ovum is, histolpgically speaking, only an epithelial cell, although we should not forget that, physiologi- cally, it is something more. Now, as the mode of cell-genesis just put forth was based upon studies of epithelial cells, the inference should be valid, that ova are formed in exactly the same way. The results obtained by Prof. Agassiz, as to the formation of ova in the Ascidian MoUusca, are in complete accordance with this view.* To these I may add my own results, incidentally obtained over quite an extended range of the animal kingdom, from the genus Tubullaria of the Radiata, to some of the higher forms of the Vertebrata. A detail of all these observations would be quite lengthy, and in this place unnecessary, however interesting they might be when written out as a special subject. I will here state the results I have obtained with the class of Birds, and they may be taken as a very good exponent of the others, made in the other classes of the animal kingdom. At the approach of the period of procreation, there appear in the * Proceed. Amer. Assoc, for the Advancement of So. second meeting. Cambridge, 1849, p. 157. VOL. VI. — 43 666 THE CELL: ovarian stroma, numbers of minute yesicles, or utricles, of a globu- lar shape, and too small to admit of a very definite description. These increase apparently by simple expansion, and when just visible to the unaided eye, are filled with fine granules or utricles. At the next stage of development, a partial replacement of these utricles by a vesicle is perceived ; and although I have been unable to watch the phases of change, yet I cannot but believe that it occurs by the same processes as those belonging to the formation of the nucleus, as we have just pointed out. This vesicle or nucleus, at first very small, increases quite rapidly, and in it is formed another vesicle or nucleus, constituting the third of the series. You have then the ovum, which is a great compound cell, the liquid of which is filled with granules constituting the vitellus* — the nucleus constituting the germinal vesicle — and in this last the nucleolus, or germinative dot. Formation of OTum as observable in birds, a. First appearance of OTum ; as a sac filled witli granules. h. The same, with a condensation towards centre taking place, c. Condensation finished, a clear vesicle appearing, d, e,f. The same changes repeated, ending in ovum (/), consisting oivUellus, germinative vesidCf and genninaiiv& dot. This whole series, however, is not formed until the ovum, as a whole, has reached considerable size, or nearly that of the adult, at least with birds. This germinative dot may, as a vesicle, expand, and have within it several nuclei, as is not unfrequently seen. Such are the phenomena as occurring in the class of birds. But with some of the other classes of animals, there occur peculiarities which will serve to illustrate the real nature of the genesis. On * By a kind of condensation of peripheral layer of these vitelline granules, a mem- brane may be formed, constituting the so-called vitelline sac, which is pretty constant in the higher animals, but which is equa% absent in many of the lower ones. This subject of a vitelline membrane, however, is one on which all are far fi-om being agreed. I will only add that, among the Mammalia, it is admitted by Valentin, Wag- ner, Wharton Jones, and some others, while the opposite is the opinion of Baer and BisohofT. ITS PHYSIOLOGY AND PATHOLOGY. 667 this account, I will here allude to some of them. In many of the articulata, and especially in the classes inseeta and arachnida, the v ova not unfrequently contain several nuclei or germinative vesicles. This was first pointed out by Herold.* But I have frequently noticed- it in a series of investigations upon the embryology of spiders, made a year or two since, and in which I have carefully figured this pecu- liarity under its many forms. These facts go to show that the rela- tions of the germinative vesicle to the ovum, are the same as those existing between the nucleus and the cell — that is, it is a secondary formation ; and, as occurs often in cells, there may be a plural pro- duction. Moreover, it would appear from this fact that, however important the germinative vesicle may be in the evolution of the new being, it does not hold a single or unital relation to the ovum as a whole, as would necessarily be true were the Schwann mode of formation here admitted.f The vitelline substance is, as is well Fig. i. Ova of common Spider (Agelena ncBvia), showing plurality of germinative Tesicles (nuclei). (Magni- fied 60 diameters.) known, composed of cells ; and these appear to be formed, according to both the direct observations of Prof. Agassiz and myself, in ex- actly the same way — by the expansion of primordial utricles, in which cell-contents are developed. In stating these views of the genesis of the ovum, I am well aware that I am taking grounds quite dissimilar to those advocated by many of the physiologists of the day. The researches of Wagner, Valentin, and others, all advocate exactly the inverse method of production, that is, that the germina- tive dot exists as the primary part, upon which the germinative vesi- cle and vitellus are built up. Such also is the view which Schwann * Herold, De Aranearum generatione, Marburg, 1824. f Recent embryological studies, and especially some upon insects, have led me to think that altogether too much Bignifiicance has been placed upon the agency of the germinative vesicle in the primitive changes of the ovum. In the Aphides, I have ob- served the egg-buds develop exactly as though they had been true eggs, and yet they have no trace whatever of a germinative vesicle — being nothing but an oval mass of nucleated cells. 668 THE cell: very naturally has taken ; for, as is true of myself in relation to the cell theory I have advanced, he sought the same class of phenomena in the genesis of the ovum, which is really only a cell, as in the cell -itself. Farther researches in this direction must remove these differences ; and although dissimilar opinions must always be expected, yet there may be equally looked for a greater uniformity of results, from the modern improved means of observation.* * Owing to the importance of the subject, to look at it in an historical point of Tiew (and which also might serve to make clear some of the obscure points), will not be a useless task. The anatomical relations of the ovum were known long before cell- studies, as such, were commenced. But the recognition of its particular parts as essential for certain functions does not date back many years. The germinal vesicle was recognized by Purkinje, in 1825, and called after that by his name. In 1827, Baer discovered the ovum of the Mammalia, which, however, he identified with the germinal vesicle of birds as pointed out by Purkinje. This point, however, was pretty clearly settled a few years after, by Coste, Valentin, and Wharton Jones. In 1835, Wagner pointed out the germinative dot and its relations. , And it may justly be ques- tioned if embryology could have been understandingly studied, that is, as to all the functions of the ovum, until these points were made out. , Tor investigations as to the formation of the ovum, considered as consisting of the three above-named parts, we must refer to those of Krause, Valentin, Wagner, Mar- tin Barry, Wharton Jones, and Bischoff and Baer. They seem by no means to have arrived at uniform results. According to Wagner, Krause, Martin Barry, and Baer, the germinative dot exists first, and the remaining portion of the ovum is formed ac- cording to the Schwann mode of cell-formation. This, however, is not the opinion of Valentin and Bischoff. The latter believes that the germinal vesicle exists primarily, in which is formed the germinative dot, and around which, by an aggregation of gra- nules on its periphery (and not according to Schwann's method) is afterwards formed the vitellus. In other words, the formation of the ovum is mi generis, and having no analogue in the production of any other tissues. Of late, and since the publication of these writings of those who may be justly called the fathers of the science, the whole subj eot has been studied iu a very thorough manner. I cannot pretend here to even allude to the various opinions put forth, and a history of the whole matter would be a volume of itself. It is evident that at least three distinct opinions beside my own exist as to the mode of ovum genesis: 1st. That of Wagner and others, which is according to the Schwann mode of cell-formation. 2d. That of Bischoff, which is, that the germinal vesicle exists first, the other parts being formed within and around it,-as before mentioned. 3d. That of Bergmann, who thinks that the ovum as a sac is first formed, and subsequently the germinal membrane and its contents are formed in it. This is at least enough to fully show tlie unsettled state of the subject. As the views of Bergmann resemble my own, as above stated, more closely than any other, I will, for a moment, refer to them. His observations wei'e upon the ova of the frog and the salamander. According to him, the vitellus at the commencement of its development consists of granules. These first arrange them- selves into large groups, then divide into smaUer ones, around which vesicles are formed by means of «■ viscid substance; you have these numerous cells filled with granules ; and the whole contents arc formed in a like manner. ITS PHYSIOLOGY AND PATHOLOGY. 669 I cannot, with some, and especially Bischoff, regard the ovum as having a special formation, because it is an ovum. On the other hand, I naturally look to its genesis as a true exponent of those ele- mentary processes of organization occurring in the tissues, of all of which it is the real parent. The genesis of the sperm cell is exactly like that of the ovum ; this is a point concerning which I have devoted considerable time, much more than to that of the ovum. Moreover, the ease of study of its phases of development is much greater. I have seen no evi- dence of its formation according to the Schwann mode of cell-forma- tion, but it follows exactly in the line of that of common epithelia. As is now very satisfactorily determined, the ovum and sperm-cell are the true analogues of each other ; their similarity of genesis would justly have been inferred from this fact alone, and hereafter, when treating of spermatic particles as special formations in cells, the other relations of the subject will be discussed. But, without forestalling those remarks, I will only add that, the evidence of this analogy being conclusive, the histological signification of the ovum as a cell is placed beyond all doubt. And as a cell we are entitled to seek for it, a priori, the same kind of genesis that belongs to cells in general, a point which I have just sought to establish. II. Chyle and Blood-cells. After those of the ovum and sperm-cell, the genetic relations of these cells next demand our consideration, for they are the first free and independent cells formed in the embryo, and are those by whose nutritive agency the others, which are united into con- tinuous tissues, subsequently acquire their development. I am well aware that, in entering this field, I am taking hold of one of the most intricate and interesting of physiological subjects, and on which account, therefore, there are not only various but widely dis- similar opinions. My own observations, made for the purpose, entitle me, perhaps, to an opinion which is difierent from any I have seen, but it cannot be satisfactorily illustrated without that brief historical retrospect of the whole matter which will enable us to learn its phases of progress ; a labour which, as to many other points also, cannot fail to be instructive. The existence of these peculiar bodies (blood-cells) in the blood, was first noticed by Leeuwenhoek,* in 1674. It was sufficient for * Leeuwenhoek ; Opera omnia, &c. Leyden, 1687, ii. p. 421. 670 THE cell: him to recognize them as corpuscles, and as having a constant pre- sence in that liquid. For nearly the succeeding hundred years, although their presence was well known to many anatomists, but little advance was made in a knowledge of their nature. In 1776, Delia Torre* described them as little rings, having a dark centre, and he has figured their piling or clustering together which occurs during coagulation. But the first researches which are entitled to the name of complete were made by H!ewson,t whose works were published at about the same time. As he appears to have had better means of investigation than the others who preceded him, his ideas of many of the peculiarities of these bodies are quite clear. We cannot wonder that he should have described the human blood-corpuscles as having a dark body or nucleus in their interior, when many ob- servers of the present day persist in the same view. Owing to the publication of the results of Hewson, many new and curious inves- tigations were made upon this subject, and that, too, over quite a range of the animal kingdom. I pass over here a review of those many writers who immediately followed this physiologist, and who have carefully noted the anatomical peculiarities of these cells as they occur in different animals (for these are secondary points to the subject of their genesis), to the writers to whom we will now direct the attention. Any investigations of this kind cannot be said to have been made until about the time of the appearance of the cell-doctrines of Schleiden and Schwann. As we have already seen in the history of cell-doctrines, SchultzJ was the first who prosecuted these studies with success. He speaks of the blood-corpuscles of the chick as being formed around the yelk-globules, the latter existing as nuclei, from which arise vesicles, according to the Schwann method of cell-forma- tion, although at that time Schultz probably had no idea of the sig- nification of these processes. * Delia Torre; Nuove Osservazione Microsoopisohe, Naples, 1776, p. 82. f Hewson; Experimental Inquiries, &o. London, 1774-77, part iii. Or the repub- lication of his works by the Sydenham Society. Edited by Gulliver, p. 220, et seq. Hewson was the first, I think, who pointed out the fact that the blood-cells of embryos and adults are different. Thus, he says, that those of the embryos of the viper and the chick are not flat and elliptical, but globular, and larger than those of the adult. This was an important fact to be learned. } Schultz; Das System der Circulation, &c. Stuttgard, 18.36. In a chronological point of view, the observations of Baumgaertner (Beobaohtungen ueber die Nerven und das Blut, &c., Freyburg, 1839) should be mentioned first. He describes the formation of the blood-oeUs in the tadpole, by the aggregation of numerous granules around a central nucleus ; these liquefy and form a membrane, and thus the corpuscle is formed (p. 40). We shall refer to this point on a subsequent page. ITS PHTSIOI.OGY AND PATHOLOGY. 671 In the embryology of Valentin,* published about the same time, a different opinion is maintained, from observations made since upon the same animal. Valentin regarded them as particular formations from the contents of the vitelline globules, -which last, he affirms, are twice the size of the blood-cells. This formation takes place in the first liquor of the blood, which, he says, is completely transparent. At this time, the constant presence of white or uncoloured cor- puscles in the blood of vertebrates did not escape attention, and after Vogelf had pointed out their peculiarities, there naturally fol- lowed many speculations as to their nature and use. That they were the younger forms of the red cells, was first put forth by Wagner and Valentin,! a doctrine which, as we shall soon perceive, is advocated at the prelsent time. This view appeared to derive weight from a second series of investigations made by Schu]tz,§ who affirmed that the coloured capsule was principally formed during the process of respiration. In the next year Schwann's|| observations appeared, and although he expressed no opinion based upon his own researches, yet, from the evident cell-character of the particle, he naturally looked for its genesis according to the usual cell mode, and in support of which he falls back upon the results of Schultz. E,eichert,Tf in the year following, entertains the view that the blood-cells are special formations in the embryo, but out of the ma- terial furnished by the vitelline cells, and therefore resemble the primary cells of the organs generally. This opinion is also that of Bischofi",** at least with the oviparous vertebrates; but with the Mam- malia, Bischoff regards the blood-cells as metamorphosed vitelline globules. As to the formation of the blood-cells in the adult animal — the point now under discussion, Reichertf f entertains the singular opi- * Valentin ; Handbuoh der Entwickelungsgesehiohte des Menschen, Berlin, 1835, p. 296. At this time, Valentin's views do not appear to have been clear and explicit, although subsequently he may have made them so. f Vogel; Physiologische pathol. Untersuoh, &c. Erlangen, 1838. J Valentin; Repertorium, 1887, p. 71. § Schultz; TJeber die gehemmte AuSosung und Ausohirdung der Verbrauohten Blutblaschen. Hufeland's Journal, Apr. 1838. II Schwann; Mikroskop. Untersuch. &c. Berlin, 1839, p. 75. T[ Reichert; Das Entwickelungsleben, &c. Berlin, 1840, p. 243. ** Bischoff; Traite du d^veloppement de I'homme, &o. Trad. d'AUemand, par Jourdain, Paris, 1843, p. 282. Il Reichert. This is what Simon says is Reiohert's opinion, as he learned by a pri- vate letter. Vide Simon's Chemistry of Man, Syd. ed. vol. i. p. 122. 672 THE cell: nion that they are the immediate production of the liver, and that this is the function of this organ. Henle,* who has paid some attention to the subject, entertains the view that the coloured cells are formed from the lymph-cor- puscles ; and he regards the lymphatic glands as the chief, though not exclusive seat of the changes thus to ensue.f The views of RemakJ deserve here an especial mention, not only from their plau- sibility, but because their real nature is fully illustrated by pheno- mena recently observed. His opinion is that they were formed in large parent vesicles, which entirely disappeared after the formation had taken place. These large vesicles he found in the lowest stratum of blood drawn from some of the higher animals, which had been allowed to stand for a time. His experiments were quite numerous, but they wanted completeness; moreover, his observations have not been verified, and there are good reasons for believing that the phe- nomena here observed were of an abnormal and not a healthy cha- racter. § * Henle ; Anat. G^n^rale, &c. Trad, de TAllemand, par Jourdain, Paris, 1843, t. i. p. 491. Also, as given by Simon from private letter ; Chemistry of Man, vol. i. p. 121. f Henle; as given by Simon: Chemistry of Man. Syd. ed. vol. i. p. 121. Vide also Trait6 d'Anat. G^n^rale, &c. Paris, 1843, t. ii. p. 103. J Remak; Medicinisohe Zeitung, July 7, 1841. § The phenomena here noticed by Remak, have been met with only as connected with pathological products, or under abnormal conditions. They may be seen often in extravasated blood, and appear to consist only of a group of blood-cells, around which has been thrown a plasmatic membrane, inclosing the whole as in a sac. This may be well observed in the blood of the elephant. Thus formed, contents of a very heterogeneous character may be brought together. See KoUiker; Zeitschrift fiir Rat. Med. bd. iv. p. 89. Also, an article in Edinburgh Monthly Journal of Medical Science, Sept. 1851. This point has considerable interest from other connections. It is well known that in the spleen of the higher and lower vertebrates, and especially the latter, there are often found peculiar bodies which sometimes appear as sacs filled with blood-corpuscles in different stages of dissolution. With these and the like data, KoUiker has advanced an unique view of the function of the spleen, viz., that it is the organ for the dissolu- tion and destruction of the affected blood-corpuscles. The support of this view he has undertaken at considerable length ; see art. Spleen, in the Cyclop. Anat. and Phys. and his Mikrosk. Anat. &c. Bd. ii. Milz. This view seems to have met with anything but the approval of other observers. Some have even denied that these saccular bodies in the spleen existed at all, while others regard them, when present, as quite accidental. For myself, after having given several weeks' examination to the subject, and espe- cially in conjunction with that of the function of the spleen, I must also dissent from KBUiker's views. My observations extended over great numbers of each class of the vertebrata, and, although I have very frequently found the bodies in question, yet ITS PHYSIOLOGY AND PATHOLOGY. 673 A short time after this, the subject was taken up and treated in the most thorough manner by Mr. Wharton Jones,* and, considering the wide range over which his observations were carried, and the apparent care with which they were performed, they are certainly the most complete of any we as yet possess ; moreover, they are now regarded as of authority on this subject. I shall therefore take them up rather in the manner of a discussion. Jones has undoubtedly laboured to establish a unity of mode of formation of these bodies, not only among the Vertebrata, but even among the Invertebrata. I trust, in making a brief rSsuniS of his results, I shall not obscure this already sufficiently obscure subject. Mr. Jones regards the chyle-corpuscle as the basis of the true blood throughout the Vertebrata. It is the starting-point from which all coloured cells must take their origin. In all the vertebrates below Mammalia (birds, reptiles, and fishes, in which the coloured corpuscle is distinctly nucleated), this formation takes place in the following man- ner : The chyle-corpuscle is at first a coarsely granular, nucleated cell ; it begins to increase, and its surface becomes finely granular. From this stage, it passes on to having a smooth, clear membrane, and a well- defined nucleus, but is still colourless and globular. The next stage is that in which it assumes its colour and shape, and is then the per- fectly formed coloured nucleated cell of these three classes. In Mammalia, however, a farther development takes place, for this cell- membrane bursts, and the nucleus of this cell escapes, constituting the true blood-cell ; therefore, the red blood-cell of the Mammalia is not the analogue of the red blood-cell of the three other classes of the vertebrates, but of the nucleus of the blood-cell of these last. In other words, the blood-cell of Mammalia corresponds to the products of the blood-cells of birds, reptiles, and fishes ; and, on this account, is regarded a higher formation. In support of the view of the nature of the nucleated blood-cell, met with in the classes below Mammalia, he describes the phases of formation as he saw them in the blood of frogs. For these details, I must refer the reader to his own account. As to his view of the from what I have seen of them, from the elephant to the eel, I can regard them only as accidental formations, or at least as bodies which have no special function. For some farther reference to the subject, see Handfield Jones, Lond. Med. Gaz. Jan. 1847, pp. 140, 142 ; Ecker, Zeitsch. f. ration. Med. tI. p. 264 ; Virchow, Arch. f. path. Anat. u. khnische Med. i. pp. 452, 483 ; Funke, Ueber das Milzvenenblut, in Henle und Pfeufer's Zeitsch. i. 1851; Remak, Miiller'sArch. 1852, Feb. ; and Wharton Jones, Brit, and For. Med.-Chir. Eev. January, 1853. * Wharton Jones ; Philos. Transact. 1846, p. 63, et seq. 674 THE cell: nature of the blood-cell of the Mammalia corresponding to the escaped nucleus of the developed lymph-corpuscle, he remarks for its con- firmation that, throughout Mammalia, there is an almost exact corre- spondence as to size between the nucleus of the coloured nucleated cell and the true blood-cell. This coloured nucleated cell (correspond- ing to the true blood-cell of birds, reptiles, and fishes) he has never seen in man, but thinks he has observed it in the horse and elephant. In the embryo of Mammalia, he finds appearances agreeing exactly with the above view of the whole matter. Thus, in an embryo-ox of one and a quarter inches long, he found three kinds of cells in the blood, viz. : coloured and uncoloured nucleated cells, and the true blood-cells ; thus having in the same liquid the elements of mamma- lian blood and that of vertebrates below it. These last-mentioned phenomena, as observed in the embryo, coin- cide pretty closely with those observed by Kblliker,* who thinks that the embryonic blood-corpuscles are metamorphosed vitelline cells; but, in regard to the formation of the blood of adult vertebrates, he ad- vocates the view that the coloured cells are the chyle-corpuscles directly transformed. On this point, therefore, he difiiers widely from Mr. Jones. I have mentioned this fact to show that the ob- serving of the appearances in the embryo, which Mr. Jones "has described, does not oblige one to adopt his view of the genesis of blood-cells in the adult animal. These opinions of Jones I have not been able to reconcile with the appearances I have met, in studying this subject. And, in de- scribing my own observations, I shall point out the grounds of dis- belief in the view that, in the three lower classes of the Vertebrata, the coloured cell is the chyle-corpuscle developed and enlarged. But, in the Mammalia, a still wider discrepancy exists, and there are two points for which I have not been able to find the least ground for their reconciliation. The first of these is, the absence of the so-called colourless nucleated cell in the blood of adults, which should be found in great numbers ; because, according to Mr. Jones, they are the parents of the true blood-celLf The second of these is, the uniformity as to size of the chyle-corpuscle throughout the Mammalia ; while, as is well known, there exists a very wide varia- tion of size with the true blood-cell. In some, the chyle-corpuscle * KoUiker, Henle und Pfeufer's Zeitsohrift, iv. 1845-46. t Mr. Jones speaks of finding the colourless nucleated cell only in the elephant and horse, among the Mammalia. I have often, and quite oai-efuUy, examined the blood of the elephant, but hare failed to observe the nucleated cell here aUuded to by Mr. Jones. ITS PHYSIOLOaY AND PATHOLOGY. 675 and the blood-cell being about equal, as in man and the quadrumana; while in others, the former is three or four times the size of the latter, as in the musk-deer and goat. It is true that, in nearly all, the blood- cell is smaller than the chyle-corpuscle. But, according to the state- ments of Mr. Gulliver,* this is not true with some of the larger pachyderms, for instance, the elephant, in which the blood-cell is much the larger. Moreover^ the size and general aspect of the true blood- cell hold certain invariable relations with the relative position of the animal as determined by a classification based upon other data. This fact, taken in connection with the great uniformity of size of the chyle- corpuscles, would lead us justly to infer, that, while these last possess only the common relations of cells, floating in a plasma, the true blood-cells have connection with the whole animal as a distinct and specific being. If this inference is correct, it at once shows how we are to regard the mutual relations of these two kinds of cells as existing in mammalian blood. There is one other point to which allusion should be made. It is the diflSculty of reconciling the oval shape of the blood-cells in the camel tribe, with the view that they are the nuclei of larger and colour- less cells which are globular ; for in the blood of all the oviparous vertebrates the nucleus has the shape of the blood-cell itself, which is oval; moreover, in all our cell-studies, it is the law that the nucleus and cell agree, at least in this particular. Mr. Jones refers to this point, and thinks the matter made clear, when he affirms that, in the Paca, the blood-cells become globular after the addition of water. He perhaps forgot that this same phenomenon occurs when water is added to the blood of any bird, reptile, or fish, and therefore this explanation is insufficient.f Since the memoir of Mr. Jones, and up to the present time, there have appeared numerous detached papers on the subject, but most of them have wanted completeness.J * Gulliver, Proceed. Zoolog. Soc. London, No. olii. I should mention, however, that my own observation does not agree with that of Gulliver ; for in elephant's blood, which I have examined, I have found the red cor- puscle to be 1-4500 of an inch in diameter, and the white only 1-2000. f I have recently had an opportunity to examine the blood of the common lama {^Auchenia paca, lUiger). The corpuscles were quite oval, being 1-3000 of an inch in length and 1-6000 in diameter. It is true that, like those of a frog, they became of a more spherical form by the addition of water, but they did not, by any means, lose their oval shape. J I have not thought it proper to burden the general text with even an allusion to these many and varied writings. But, in an historical point of view, some of them 676 THE cell: I do not think that the views of Jones have been acceded to by most physiologists. Among these, may be notably mentioned Dr. Car- penter, who has advocated the distinct nature of the chyle-corpuscles, both as to function and distinction, believing that the blood-cells are special formations.* Mr. Hassallf entertains a similar opinion. But after all, the subject is in quite an unsettled state ; and this is so be- cause the opinions, justly deserving that name, of most observers have been formed more from, negative than from positive data. Whatever view we may take of the origin of the blood-cells and their relations to the chyle-corpuscles, this much is certain, that the materials of their formation in the adult are derived from the chyle. Therefore, in considering the histological relations of the latter, we shall be most likely to get at correct views of the genesis of the former. This I propose to do first : and whatever views we may thus obtain of what is properly the reproduction of these cells in the are worthy of a brief notice in a note like this. I will go back to a few years pre- ceding Mr. Jones's paper. In 1842, Mr. MoLeod published his observations upon the development of the blood-cell in the chick, and which appear to be different from those either of Schultz or Valentin, before mentioned. According to him, in blood taken from the heart of a chick of three days, are found " a number of small granules floating in the field ; these enlarge and become clearer in the centre, and when they have gained twice their original size, the central clear part becomes dull, and in a short time it is seen to be distinctly granular. The enlargement of these bodies, with the granular appearance of their centre, seems not to depend on the aggregation of granules round a central one, but on a property which they have in themselves of en- larging and presenting that figure. During all this time they are quite spherical. In the second stage, the central portion gradually becomes less opaque, and ceases to appear granular. It then has the appearance of a slightly flattened round cell, with a nucleus in the centre. The cell is disk-like, rather concave, but the nucleus convex. In the third stage, this concavity disappears, and the whole becomes slightly convex." ( Vide London and Edinb. Month. Journal, Sept. 1842.) It will be perceived that the mode of genesis, here described, corresponds quite closely with that which I think belongs to cells generally. Donn6 advanced the view that the spleen is the great elaborator of the coloured blood-cells. (De Vorigine des globules du sang. Stance de I'Acad. 7 Mars, 1842. ) Kra- mer has watched the development of the embryonic blood-cells in the frog. He says they are first embryonic cells, and then pass through a series of changes, ending in the perfectly formed corpuscles. In the adult, he is of the opinion that the chyle-corpuscle is transformed into the blood-cell by a clearing up and colouring process. ( Vide Miil- ler's Arohiv, 1848, p. 63.) Mr. Paget found the blood of a foetus of one month to consist of nucleated cells, some of which had two nuclei, and were ovoidal. ( Vide London Med. Gaz. Feb. 2, 1849.) • Carpenter, Principles of Human Physiology, &c. Amer. ed. 1853, p. 169, et seq. f Hassall, the Microscopic Anatomy of the Human Body, published in Fascio. Lon- don, 1847-51. ITS PHYSIOLOGY AND PATHOLOGY. 6T7 adult, they can well be subsequently considered in connection with what we shall learn of what is properly their primitive genesis in the embryo. If we take the chyle, as it is just forming, from the smaller chyle-vessels, we find it composed of a blastema, having a univer- sally dotted or minutely granular aspect ; or, in other words, com- posed of a hyaline liquid, in which float innumerable minute par- ticles. These last constitute its only solid particles, and give the chyle its milky aspect. If we examine that taken from larger vessels, and those nearer the thoracic duct, we find, among these granules, small cells or vesicles. These are quite small, and appear to be simply vesicles, having only a hyaline liquid for their contents. There appears to be little doubt that they have not arisen except by the expansion of these primordial granules or utricles — ac- cording to the first processes of the method of cell-genesis I have already pointed out. Their simple, vesicular, hyaline aspect shows that they could not be formed around a primary nucleus, according to the method of Schwann. Once thus started, they go on increasing by dilatation ; their liquid contents become granular, and some of the gra- nules adhering to the inner surface of the sac, give the whole that well- known finely granular or nebulous aspect. Afterwards, the free gra- nules in the interior partially centralize themselves, giving rise to the granulated nucleus. Such is the nebulous, granular-nucleated cell of the chyle, as met with in the thoracic duct. These characteristics become more and more pronounced, as the chyle approaches its iii- flux into the general circulation. Thus far the subject is pretty clear and well understood. The chyle-corpuscles pass into the gene- ral current of the circulation, and, in so doing, it is evident that they become subservient, either directly or indirectly, to the forma- tion of the coloured cells. This opinion, aside from any observations, could be justly inferred from their decreased number — being appa- rently replaced by the true blood-cell. Were this not so, we might justly ask, " What becomes of all the chyle-corpuscles ?" This subserviency, according to my own observations, is direct in the oviparous vertebrates, but indirect in the Mammalia. In birds, reptiles, and fishes, the chyle-corpuscle is the nucleus around which is formed the true blood-cell. I will here describe the phases of this development as seen in reptiles, the Anourous Batra- chians. In the blood of these animals, after they have been well fed, two kinds of corpuscles are seen, and in nearly equal number. The first are small spherical or slightly oval corpuscles, having a dis- 678 THE cell: tinctly marked, granular, punctiform aspect. These are the chyle- corpuscles. The second are the well-known oval, nucleated, lenticular Fig. 5. t- n " O* '■ of ^^* ® ^'' m § Formation of chyle-corpuscles, taken from lymphatics of a goat. a. The first solid particles occurring In the lymph-liquid, and giving it a pellucid aspect — these are utricles. &. The same, increased in size by expansion, c. Still larger, with a few granules in the contained liquid, d. Contained liquid crowded with granules, the whole forming the chyle-corpuscle. (Magnified 250 diameters.) bodies, the coloured cells being about three times the size of the first. The blood, thus composed, is to be examined without water, and even then the appearances of a formative process will not be seen at first. Many of the granular corpuscles appear only as such, but with a good light and a clear defining power, a delicate and almost transparent membrane will be perceived encompassing some of these corpuscles; at first, it is seen lying quite close upon it, but by the addition of a little water it is made quite distinct. With a few, this newly-formed membrane may be seen standing ofi', quite distant on all sides, from the granular nucleus. But it is so delicate that, after expansion to a considerable extent, it is nearly always ruptured by the pressure between two plates of glass. Until it has reached to about half the size of the adult cell, it is spherical and colourless. But after this, several notable changes begin to take place. The nucleus, hitherto coarsely granular, assumes a finely punctiform aspect, and finally the granules almost entirely disappear ; it then has quite an even and smooth appearance. After this, both it and the cell-membrane, by which it is surrounded, begin to assume that oval and lenticular shape seen in the adult form. The contained liquid has a faint reddish hue, and so it may be said that they are partly coloured. These changes, thus begun, continue, and end in the perfectly de- veloped form. In some instances, however, the routine is a little different ; the " clearing up " of the granular chyle-corpuscle takes ITS PHYSIOLOGY AND PATHOLOGY. 679 place simultaneously -with the formation of the new membrane around it, so that you have one clear cell contained within another. Then again, these chyle-corpuscles may assume a slightly oval shape before the enveloping membrane is formed ; thus seeming to show that the idea of their future development is persistent in them, before any steps for its ulterior manifestation have been taken. Aside from the evidence of this view of the matter, by direct observ- ation of these changes, it is also supported by the fact that there is a close agreement as to size between tl^e chyle-corpuscles and the nuclei of true blood-cells. Not only does this hold true of the blood of reptiles, but also of that of birds and fishes. Moreover, as far as my Fig. 6. Oy ^.o ^ J)^ Formation of blood in oviparous vertebrates. {Salamandra glvMnom.) a. The Cbyle-corpuecles. 6. The same surrounded by a delicate membrane. e. The chyle-corpuscle become clear by a dissolution of the granules, the whole appearing as one vesicle within another, d. The membrane observed at 6. increased, and having an oval shape, e. The well- formed corpuscle, having an oval nucleus partially clear — the whole coloured. These figures illustrate what I have observed with birds, and very many other reptiles. (Magnified 250 diameters.) own observation goes, the chyle-corpuscles are smaller than the true blood-cells, throughout these three classes* — thus making it explica- ble that the latter should, in every instance, be formed around the former. In the cartilaginous fishes, in which the blood-cells are • I have found this true of the smallest birds I hare examined — and in these, above all other oviparous vertebrates, a deviation from the common rule would be most looked for. I do not know how it may be in the humming-bird ; but Dr. Davy says, that here their long diameter is 1-2666, and their shortest 1-4000 of an inch, but he does not mention the size of the chyle-corpuscles. ( Vide Proceed. Zool. Soc. in Ann. Nat. Hist. July, 1846.) 680 THE cell: quite large, much more so than in the osseous ones; and in all the reptiles, these relations are easily seen and satisfactorily made out. In birds, however, they are less clear ; but in no instance have I met with appearances not reconcilable with — in fact, which did not demand — the above view. The nucleated blood-cell belongs to the oviparous vertebrates alone ; and I know of no instance in which it has been, met with in the blood of adult Mammalia, at least, as a distinct and uniform body. In the blood of Mammalia, a different condition of phenomena is met with. The perfectly formed blood-cells have no nucleus, but consist, each, of a lenticular, generally round vesicle, in which may occasionally be seen a few minute granules. Generally, the white or chyle-corpuscles are the larger; and, as in the lower classes, they possess no regulai-ly formed nucleus as a single body, but have in their centre, to correspond to it, two, three, four, or even more granules, which are of a quite uniform size and appearance. The want of all correlation of size between these chyle-corpuscles and the true blood-cells or vesicles, appears to me to forbid the opi- nion that the former, as such, are directly concerned in the genesis of the latter ; either being produced in them, according to the view of Mr. Jones, or around them, as is the opinion of Schultz. My own opinion is, that the blood-vesicles of Mammalia are formed around the granules which constitute the compound nucleus of the chyle-cell, and this takes place in the same way as that of the blood-cell in oviparous vertebrates around the chyle-corpuscle itself; the nucleus afterwards becoming dissolved, and, in nearly every in- stance, entirely passing away. In procuring the blood from living mammals for examination, we generally take it from some of the terminal capillaries, and such, therefore, as has traversed the whole line of the circulation. On this account, the phases of the genesis are not well marked, and sel- dom ever seen ; the whole field appears, at first, occupied with only two kinds of bodies, the vesicles and the white corpuscles ; and, in many instances, these changes have been so completed, that nothing else can be detected after the most careful search ; but, generally, a little attention will show that a third form exists. This is a small spherical cell, slightly coloured, and in which may be often seen a few minute granules. These cells are few in number, and vary in size from that of one- ITS PHTSIOLOST AND PATHOLOGY. 681 third to that of two-thirds or more of the size of the adult vesicle. These I have regarded as the newly forming blood-vesicles, the nucleus of which appears to disappear at a very early period ; and, unless attention was directed to the point, they would not, on that account, be distinguished from the adult form, even although only two-thirds its size. Fig. 7. , (oy ® ^# & ® 9 4% © ®^® m ® Formation of mammalian vertebrate blood. (Man.) a. CIiyle-corpuscleB. &. The same treated with acid, showing nuclei, u. The escaped nuclei free. d. The nuclei with a delicate colourless membrane, e. Well-formed blood-corpuscles — having a dark or light centre according to focus. /. Blood^sorpuscles with granules — the remains of old nuclei. I take here the instance of man, because his blood is always accessible ; but the same phenomena can be wit- nessed with other higher animals. (Magnified 350 diameters.) The fact that these phases of formation do not appear boldly dis- tinct in our observations, is due, I think, firstly, to the rapidity of the genesis, and, secondly, to the fact just mentioned, that the speci- mens observed are generally from the terminal capillaries,' by the time they have reached which, owing to the rapidity of formation, these changes are entirely or nearly completed. In a liquid like the blood — the nutritive one of all the economy, and which is full of a formative plasma constantly in motion, and which has its vitality repeatedly renewed by respiration, the escaped nuclei of the chyle-corpuscles rapidly gather about them, each a plasmatic membrane, which, from the constant motion, is as rapidly expanded and developed. Aside from the support which I think this view has from observed phenomena, it is the only one, in my opinion, that does not meet with overruling objections. I will here allude for a moment to some of these last, which are constantly occurring. The view of Wharton Jones is, that the blood-cells are the escaped nuclei, perfectly de- VOL. VI. — 44 682 THE cell: veloped, of the chyle-corpuscle ; while that of Schultz is, that they are formed around the latter. Now, we will take the blood of man and of a goat ; for, in them, the chyle-corpuscles are of about the same size, and larger than the blood-cell. It is, therefore, at once evident that the view of Schultz cannot be here maintained. On the other hand, the view of Jones meets with equally valid ob- jections. For the chyle-corpuscles being of the same size in these two animals, their nuclei (if it is admitted that they each have a single one, distinct) are also equal, and, being metamorphosed, should pro- duce the same sized vesicle ; or, at least, these vesicles should not he smaller than the nuclei. But this is not true — for, in the goat, the blood-vesicles are three and a half times smaller than the chyle-cor- puscle ; but, in man, they are only a third smaller. But these difficulties do not present themselves, if we take the ground that the genesis takes- place around the granules, which the chyle-cells contain ; for, in every instance, they are smaller than the blood-vesicles, and may therefore well serve as a punctum saliens of the development of the latter. The whole subject, however, will receive additional confirmation, when, in a succeeding chapter, we take up the functions of these two kinds of cells. In the genesis of organic particles, which, throughout a wide range of animal life, have exactly the same function, we very naturally seek a unity of mode of expression. In the present case, this feeling is gratified by the manner in which we have just viewed the whole sub- ject. It is this : the blood-vesicle in the Vertebrata is the product of the chyle-corpuscle, either as a whole or in part, ^s a whole, with the oviparous classes, in which it gives the formation a persistent nucleated character ; as a part, in Mammalia, and in which, since it was simply a point of departure, and not an individual form as in the former case, it soon passes away, leaving the part as a simple vesicle. It therefore may be stated that whereas, in the lower classes, the chyle-corpuscle is directly appropriated — in the higher, a step in advance has been taken, and the elaborated products of this cor- puscle are used in the same way. The formation of the blood-cells in the embryo necessarily involves changes considerably difierent from those of what is properly termed their reproduction in the adult. In the embryo, their first forma- tion undoubtedly occurs out of the vitelline cells, and as such they obey the general laws of cell-genesis, and are nucleated ; but it may ITS PHYSIOLOGY AND PATHOLOGY. 683 be properly asted if these are true blood-cells ? In the mammalian embryo, their reproduction takes place through the medium of the blood of the mother ; but in the oviparous classes, it is out of the material laid up in the vitellus. Now, their reproduction in the adult is out of a material elaborated from the food, which does not exist in the embryo. ' These formations, thus necessarily different, cannot, I think, mutu- ally elucidate each other's nature. Moreover, we do not yet fully understand many of the relations of embryonic life ; for there are organs which then, and then only, have a functional activity. Such are, for instance, the vascular sanguineous glands ; and recent investi- gations into their character tend to show that it is their part to elabo- rate a cell-product rich in albumen and protein, which is turned into the general circulation.* These cells are nucleated epithelial cells, which, by their association in the blood with coloured particles, might become partly coloured. Therefore, it appears to me that the fact of finding corpuscles of different appearances in the blood-liquid of mammalian embryos, is of no importance to the subject of blood- reproduction in the adult animal, in any point of view. In fact, I think it would be somewhat surprising that, in parts so newly formed, and that too out of nucleated cells, there should not then be found, ' in the vessels, cells of different aspects. I have given some attention to these phenomena as occurring in very young embryos, and it may be well that I record here what was observed, and especially as it is confirmatory of the general tenor of the views advocated on the preceding pages. My investigations have been with both the oviparous and the mammalian vertebrates. We will look to them in their order. 1. Oviparous Vertebrates. — In the chick, the blood or nutritive corpuscles first appear in that portion of the germinal membrane soon to become the area vasculosa; this is at about the twenty-seventh hour of incubation. It is not, however, until nearly a day after this that the blood-cells can be well and satisfactorily distinguished. They then appear as cells or vesicles, having a variety of sizes and shapes, both nucleated and non-nucleated, and coloured in proportion to their size. They originate in the vitalized material (oil and albumen) of the vitel- lus, appearing first as small vesicles, without a nucleus, perfectly » See a very elaborate Memoir by Professor Eoker, of Halle. Annal. des So. Nat. torn. viii. p. 103. 684 THE cell: globular, and faintly coloured. These vesicles increase by simple ex- pansion, and their red colour becomes more and more pronounced as their size becomes larger. After having attained about half their full size, a nucleus appears in their centre, apparently from a kind of condensation of the contents, exactly as I have described the nuclear formation of cells in general, on a preceding page ; that is, the central portion becomes opaque, which opacity disappears in proportion to the evolution of a distinct nuclear body. Most of the adult cells, therefore, have a nucleus, but generally it is small, and rarely central ; in fact, seeming of no service. When these changes have occurred, you have nucleated cells; but they have not their primitive spherical form, and are quite irregular. I have thought that a part of this irregularity was due to their com- pression in the newly formed vessels, while their imperfect lenticular character may be due to the fact of their being blood-cells ; and this last shape has been gradually assumed as they have been developing. Thus, it would appear that, when first formed, they originate in the nutritive blastema of the vitalized vitellus; commencing as vesicles, at first colourless, but which afterward become coloured as soon as a circulation is established, and then nucleated. Now if, after the circulation is well established, say at the end of the eighth or ninth day, the> blood be examined, it will be found composed of the same corpuscles, but which have a more regular shape and definite appearance ; still, the absence of a typical uniformity, as is in the adult, will strike the observer. The whole condition seems to be conventional or provisional. The cells are generally distinctly nu- cleated ; but the nucleus is small and round, and apparently sustains an indifi"erent relation to the whole as a simple cell. Their aspect is quite epithelial, and I am sure that, were it not for their colour, they would easily be mistaken for epithelial cells. ' Fig. 8. o a ® & /^® © ^ First formation of blood in oyiparous vertebrates, from arm vasculosa of chick of thirty hours' incuba- tion, a. Vesicles appearing in Titellus; ahnost colourless. 6. The same with a nucleus, and coloured. c. The corpuscles fully formed and coloured, haying irregular shapes. Average size l-3000th inch. (Magnif. 860 dla-n.) ITS PHYSIOLOGY AND PATHOLOGY. 685 This, in fact, -would show that they are, as we otherwise well know, simple vitelline products; for, as the ovum, vitellus and all, is, as we have seen, but a great compound epithelial cell, we should ex- pect that the cells elaborated from its contents would take on an epithelial instead of any other type. Fig. 9. ,...-. b ® ^-' ®^ ® ® ^ @ Si U (i) Blood of embryo chick of seven days' incubation, a. BloodHJorpuscles coloured, nucleated, and oval- lenticular in shape. &. The same, forming, almost colourless ahd perfectly spherical, c. The same as a, seen laterally. In regard to their constant reproduction in the embryo chick, or in fact in any of the oviparous vertebrates, I think it is merely by a repetition of the same processes as those of their formation. Kbl- liker,* Rees,t and others, are of the opinion that their reproduction is by division or segmentation, each corpuscle producing two by dividing in the middle. I have seen the class of phenomena to which these observers allude, and especially the hour-glass appearance of the globules. But, after considerable observation, I have been unable to satisfy myself that they are reproduced or multiplied in this way. In the young chick, I have frequently seen these peculiar corpuscles in the field, in the different stages of this change. In some, the shape was simply pyriform ; in others, still more constricted, so that a small globule appeared connected with a large one; and then, again, the real hour-glass form. But what inclined me to the opinion that this change is not a normal or common one, is the fact, that, in those of a pyriform shape, the nucleus remained unchanged; and also that, in those of the hour-glass form, the nucleus was in one of the parts alone; whereas, in true fissuration, the nucleus is divided as well as the cell. I am therefore disposed to regard these phenomena as I do the crenulation of blood-corpuscles in general, that is, due to en- dosmose and exosmose. ' Kolliker; Henle und Pfeufer's Zeitsch. iv. 1845-6. \ Rees, quoted in Banking's Abstract, vol. i. p. 2ol. Amer. eJit. 686 THE cell: Fig. 10. i '0 &kf The honr-glaaSj fissnrating appearance of blood-globnlea in embryo-chick of seven days. a. The glo- bnles apparently partially divided. 5. The same uneqnally sOj the naclens on one side. c. The globules before these phenomena occur. 2. Mammalian Vertebrates. — In order to see the formation of the blood in these, it is necessary, of course, to take the embryo at a period so early that no vascular connection has taken place with the mother ; and as good a time as any is when the bloodvessels are ramifying over the amnion, and just before they have formed any connection with the placental tufts. The blood then found belongs to the embryo alone, and has been elaborated by its own forces. Such was the case with the foetal goats I examined. In a foetus three-fourths of an inch in length, and fourteen days old, that is, after conception, the following phenomena were observed. The blood had only one kind of cells. These were nucleated, spherical, having a size ofjyjj^to^^ of an inch in diameter. A most careful examination showed the presence of no other forms. Now, what were these cells ? To me they appeared only as coloured epithelial ones, and certainly, with the exception of colour, they could not otherwise be described. Their average size was about four times that of those of the adult goat. I am, therefore, of the opinion that the blood-cells of the mam- malian embryo are only epithelial cells, exactly as are most of their other individual free cells, and* that they have taken the function of oxygenation provisionally, discharging it until the direct connection of the embryo with its mother, exactly as is the case with the em- bryos of oviparous vertebrates up to the time they escape from the egg' Fig. 11. i/^)) M% i^^ ^^m km %< 7 JO o ® First formation of blood in mammalian vertebrates, from f,>:tal goat of 14th day, having no vascnlar connection with the mother, bnt bloodvessels ramifying on allantois. „. Coloured nucleated blood-cells, nmformmsize and appearance. Si.e 1-1500 inch. 6. Blood-corpuscles of adult goat to show the relative size. Size 1-7000 inch. (Magnified 360 diameters.) "»»«» ITS PHYSIOLOGY AND PATHOLOGY. 687 This view of the whole matter makes this entire class of phenomena pretty clear. The Hood of embryos, as such, is of an epithelial na- ture, and simply provisional ; and therefore cannot he compared with the blood of adults, which 4s elaborated from the food, and which, holding certain typical relations with the animal as a specific indi- vidual, the corpuscles have a uniform type-character of their own. Both KoUiker* and Wharton Jones,t as above cited, speak of having examined the blood of mammalian embryos. But it appears to me that they have overlooked the fact of the necessity of such examinations being made before any direct connection with the mother had taken place. Thus, Kolliker examined the human embryo of three months, and Jones, an embryo ox of an inch and a quarter long. This can well account for their finding several kinds of corpuscles ; as, 1st, the corpuscles of the adult ; 2d, coloured nu- cleated cells ; and 3d, uncoloured nucleated (epithelial) cells ; — in fact, a mixture of adult with embryonic blood. Moreover, the " gra- nule cells," those both coarsely and finely so, which Jones alleges he found, appea^;,to me to have been only modified epithelial cells in an uncoloured state ; or perhaps the cell-products of some of the vascu- lar sanguineous glands, already spoken of. Thus far, our attention has been directed to the blood of one divi- sion of the animal kingdom — the Vertebrata. In the other division, however, quite another class of phenomena is met with. As has before been stated, the coloured blood-cell belongs to the vertebrates only. It is with them a special formation, and has a broad physiolo- gical signification when viewed in connection with their respiratory apparatus. But in the Invertebrata, the anatomical peculiarities do not demand it, as we shall hereafter learn when discussing this point. The blood or rather nutritive liquid of invertebrates has but one kind of cells. These are granular, and closely resemble the chyle- corpuscles of the vertebrates, and of which they can properly be re- garded as the analogues. This is so with the classes Articulata and Mollusca ; but in the Radiata, this liquid has even a less organized character, for with them it is only the food of the animal in a tritu- rated and partially digested condition, and contains no special cor- puscles. Wagnerf first suggested the idea that with the Articulates and • Kolliker; loc. citat. t Jones ; Phil. Transact. 1846, pp. 63-101. % Wagner ; Physiology, translated by R. Willis, p. 278. THE cell: Mollusks, the blood was chyle in ciroulation, and nothing more. Recently, Prof. Agassiz has taken up this subject, and extended it throughout the animal kingdom. "Without discussing the point here, I will only say, that he divides the circulating nutrient liquid into three kinds, viz : chyme, chyle, and true blood. The first belongs to the Badiata; the second to the Mollusca and Articulata; and the third to the Vertehrata. This view has much the semblance of truth, and is borne out by many well-ascertained facts. I shall here adopt it provisionally, omitting the consideration of some intri- cate questions which it involves. If we examine the blood of any of the Articulates or Mollusks which have a distinct circulatory sys- tem, we find in it many irregular, granulated, colourless corpuscles, which have some variation of size. These are the only corpuscles it contains, and have been called the "white blood-cells." Anatomi- cally speaking, they consist of a pale plasmatic membrane, or, more properly, involucrum, surrounding a number of granules, in the centre of which last you can, in some, perceive a nucleus. Their shape is generally spherical, but many other roundish shapes are seen. Great numbers of the same kind of granules in a free condi- tion are floating in the liquid. I think it questionable if many of these bodies have a true membrane, or, in fact any covering except one of a simple plasmatic character, such as any group of granules floating in a formative plasma would gather about them. There are others, however, quite small, which have a true membrane. As to their genesis, it appears to me, from the repeated observations I have made, that it takes place exactly like that of the chyle- corpuscle among vertebrates — by the expansion of a primordial utricle into a vesicle, inside of which are collected granules. That this is so, would ap- pear from the fact that in the field may be seen numerous pale vesicles, having a few small granules, and which are apparently these corpuscles in a developing state. After these vesicles have in- creased by expansion, the granules become more numerous; they may remain in a scattered condition in the cell ; or they may collect in the centre, and, by a kind of condensation, form a nucleus, as is sometimes seen. The corpuscles thus formed are colourless, through- out these two classes ; in the Annelids, which have red blood, this colour is not due to the corpuscles, but to the liquid in which they float. In a genetic point of view, the blood of this division, thus simply constituted, has no other peculiarities worthy of mention. The ITS PHYSIOLOGY AND PATHOLOGY. 689 anatomical questions as to the relations of their digestive with their circulatory systems, cannot be properly discussed here. With this description, I close that which relates to the genesis of normal cells, which exist in the economy, either in an entirely free and independent condition, or are never blended into tissues. ^ mi Fig. 12. # .-;/?» a # ® # o\) ® # m o O o The blood of Invertebrates, taken from Mdolvnfha subs]pi'nosa, consisting of only one kind of corpuscle, colourless, and this resembling the chyle-eorpuscle of Vertebrates, a. Corpuscles filled with granules, some of them nucleated indistinctly. 6. Their formation from vesicles, as in the case of the chyle-corpus- cles. Although the above is a representation of the blood of insects, yet the same is seen in the other classes, the ArachnidOj MoUusca, and Crustacea. We now come upon the consideration of the genesis of another class of cells, viz : those which exist in connection with, or united into, continuous tissues — of which they form the elements. This of course includes all of the other special tissues of the animal economy. Such are the Muscular, the Nervous, the Fibrous, the Oartilaginous, the Osseous, and the Adipose tissues.* III. Neevb-Cells and Nerve-Tissue. , The nervous tissue is the noblest of all in the economy, and, more than any other, has a uniformity of structure throughout the en- tire animal kingdom. It is composed of two parts, an active one, consisting of free cells, and a passive one, the agent of the former, composed of tubes, and which may be regarded as the metamor- phosed products of the cells. A consideration of the phases of genesis of this tissue, in both its simple and compound states, necessarily involves many points of discussion, which, otherwise situated, would scarcely belong to this work. As in former cases, we shall, by learning some of the historical re- lations of the subject, be enabled all the better to comprehend its de- * The epithelial cell has already been ooDsidered: therefore, thosetissues Tvhich are formed by its metamorphosis, in connection with fibrous and other tissues, cannot again come up for consideration. Such are Mucous and Serous Membranes, the Skin and its appendages, and the Teeth. 690 THE cell: tails ; I propose, therefore, a brief review of the labours and opinions of those who have heretofore studied this subject. I know of no tissue which has received so much attention as that of the nervous system. This may have been due to the fact that anatomists, recognizing its general relations to the higher conditions of life, have sought a thorough understanding of these last, by the most careful study of its elements. Then, again, I think it is true that most good working physiologists have a preference in the study of tissues ; and, if I may thus express myself, it has been the good fortune of the nervous tissue, that so many excellent investigators should have had for it such a predilection. As will soon be seen, it engaged the attention of many of the most laborious and trustworthy observers, and this too, at that period when new improvements in means of observation were getting into use, and when, also, quite as much care was exercised in observing, as at the present day. As is true of nearly all the other tissues, we must, in this case, refer to Leeuwenhoek,* as the one who first described the elements of which it is composed. This ancient microscopist has described not only the fibrous, but also the cellular structure of this tissue. Our astonishment is that, in his day, one should be able to recognize so exactly these parts, and make their proper distinctions. But the instruments of his day did not allow him to perceive any of the details of these elements. This statement obtains also for the succeeding hun- dred years; and although Ledermullerf studied it, he did not make much progress beyond what was then already known. It is true that Prochaska,! Fontana,§ and others, have left many descriptions of what they observed in studies of this kind ; but, although they may have prepared the way for subsequent discoveries, they certainly laboured under some optical illusions, besides mistaking abnormal for normal appearances. It was the opinion of Fontana, that the nerve-fibres were tubes, in which there existed an actual circulation. But it was not until after the commencement of the present cen- tury that observations were made possessing much importance. In 1816, Treviranusll made some advances ; and, although he was in- • Leeuwenhoek ; Opera, torn ii. p. 309. ■j" Ledermuller ; Miorosoopisohe Gemuths-und Augeuergoetzungen, Nuremberg, 1763, p. 63. X Prosohaska; Struotura Nervorum, Vienna, 1779, p. 68. g Fontana; Traite sur le Venin de la Vipfere, Florence, 1782, torn. ii. p. 202. II Treviranus ; Vcrmisolite-Schriften, Giittingen, 1816, p. 128. ITS PHYSIOLOGY AND PATHOLOGY. 691 clined to adopt the views of Fontana, as to the anatomical relations, he rejected the idea of a circulation. Moreover, I think he was the first to declare that the cellular and fibrous parts have the same ele- mentary constitution. As yet, the difiicult points remained to be settled, and I cannot conceive that, with the instruments then in use, this could be done satisfactorily. About the year 1830, a new impulse was given for researches of this character, by the improvements in microscopes ; and, as Henle* justly remarks, it led to nearly as many errors as truths on all these subjects ; but they were instructive errors, and, as we shall soon per- ceive, were the precursors to finally correct opinions. In 1833, Ehrenbergt took up the study of the cortical substance of the brain, and recognized, beside the nerve-cells and tubes, what ap- peared to be a third element, apparently consisting of rows of trans- parent globules, united by a delicate film. These are the now well- recognized varicose tubes, their beaded aspect being undoubtedly due to pressure, the very slightest of which is sufficient to produce it upon their filmy walls. This gave rise to a lengthy discussion, as to the nature and character of these beaded tubes — and there can be no wonder that the whole should still have remained so unsettled, when we consider that the appearance being artificial, each observer was likely to meet with dissimilar phenomena.^ Treviranus§ was the first to declare positively that these appear- ances were due to an artificial condition. In this, he was well sup- ported by Valentinll and others ; and subsequently, MUller, Remak, and others renounced their old and opposite view for this. The discovery which Valentinf soon after made, of the delicate membranous envelop of the nerve-tubes, tended to give clear ideas of the real nature of the above-mentioned phenomena. For, in the presence of this membrane, could be traced the various beaded ap- pearances. The work of Remak,** which appeared soon after, and * Henle; Traits de I'Anat. g^n^rale. Trad, par Jourdain. Paris, 1843, torn. ii. p. 340. f Ehrenberg ; Poggendorf' s Annalen, xxviii. p. 451. X Among those who participated in this discussion may be mentioned the names of Miiller, Volkmann, and Remak. § Treviranus ; Beltraege zur Auf klaerung, &c. &c. Bremen, 1835-7, ii. p. 25. II Valentin ; Ueber der Verlauf nnd Enden der Nerven, Bonn, 1836. If Valentin ; loc. citat. ** Remak ; Observationes anatomicse et microsoopicse de Systematis nervosi Struc- tura, Berlin, 1838. 692 THE cell: which is justly entitled to the name of comprehensive, opened a new field of discussion from the peculiarity of some views there entertained. Remak thought that the nerve-tubes or fibres consisted of three por- tions : 1. Of an exterior envelop of cellular tissue, which, by its local increase here and there gave the knotted aspect to the whole ; 2. A delicate membranous tube, lining the first ; and 3. A broad flat band lying within the last. This view was immediately attacked by Valentin ;* and soon after, Schwann,t in his great work, pointed out its true meaning, and fully showed wherein lay the error. But he did this by falling back upon his cell-doctrines, and seeking its true explanation in the genesis of those parts from pre-existing nu- cleated cells. In fact, I think it would have been difficult to have reached the point in any other manner. But, notwithstanding what Schwann accomplished — clearly recognizing many of the relations of the contents of the tube, yet the whole was not yet fully explained, and some phenomena were often presented apparently not recon- cilable with the above view. It was perhaps on this account that, about the same time (that is, of Remak's work), PurkinjeJ expressed a still diiferent view. He thought that the tubes had three primitive elements : 1. An exterior sheath ; 2. A soft medullary mass, and 3. A central portion, transparent, and which he termed " axis cy- linder." If I correctly understand the matter, this axis cylinder of Pur- kinje corresponds in some respects with the flat central hand of Remak. But I must confess, with Henle,§ that this point is far from being clear. But the subsequent researches of Henle|| have made this matter pretty distinct, for he has pointed out the cause of the error. The conclusion of this matter is this : The nerve-tube, when examined in a very fresh state, is found to consist of a sheath inclosing liquid contents of a pellucid aspect. In this liquid, however, changes soon occur. A kind of coagulation of it is perceived ; and that portion of it next to the sheath becomes of a white homogeneous aspect, con- stituting the " white substance of Schwann." But the central portion remains clear, and has the aspect of a nearly transparent axis. This is the axis cylinder of Purkinje. When the nerve-tube is subjected * Valentin; Eepertorium, 1838, p. 73. f Schwann; loc. ciiat. p. 174. I Purkinje ; Bericht ueber die Versammlung in Prag, 1838, p. 177. ? Henle ; Traits d'Anat. g^n(5r. &o. torn. ii. p. 344. II Henle; hc.jitat. torn. ii. chap. xii. ITS PHTSIOLOaT AND PATHOLOGY. 693 to even very light pressure, this last is forced out, and assumes a variety of globular and varicose appearances. As to the real nature of these phenomena, I shall express an opinion when giving an account of my own observations. Those discussions, therefore, which seemed to be required in order to get at the truth in these subjects, may be said, as far at least as relates to the nerve-fibres, to have ended some years since ; and this was perhaps with the labours of Henle and Valentin. It now remains, before closing this historical sketch, to notice the progressive condition of the other element of this tissue in an en- larged state — the ganglionic vesicles or cells. The existence of these bodies did not, on account of their size, escape the attention of the older anatomists who used the microscope upon the nervous tissue ; but their nature or use was not at all under- stood. And although Ehrenberg* had noticed and figured them, yet the first good description of them was given by Valentin, f He not only described them^ but noticed their caudated prolongations, and ' alluded to their similarity of form to that of the egg. J Subsequently, Schwann pointed out their cell-relations ; and since then they have not been a matter of dispute, excepting as to their anatomical rela- tions or connections with the nerve-tubes. That some direct connec- tion of such kind did exist, was first inferred from their caudated prolongations, which seemed to be very convenient to attach nerve- tubes. This was first suggested by E.emak,§ and since then, other observersll have advocated the same view. Still later, Kolliker^f has advanced the same view, stating- that in the lower animals each of these vesicles may give rise to more than one tube, but that in the higher, a single efiierent fibre is the rule. This is a point to which I have given some attention, and in closing the historical review of this tissue, it may be well to allude to my own views of the matter. Some time since, I made a series of examinations of the human brain, and that of other animals, to ascertain for myself the real nature of this point. I found no appearances justifying the opinion that a direct connection ever exists between the ganglion vesicles and * Ehrenberg; Poggendorf s Annalen, 1833, xxviii. p. 458. ' f Valentin; loc. citat. 1836, p. 77. J Valentin; Nov, Act. Aoad. Leopold, xviii. p. 196. I Eemak; Observ. Anat. Miorosc. de Syst. Nerv. Struct., Berlin, 1838. II Will, Todd and Bowman, Kolliker, &c. &c. \ Kolliker; Siebold and Kolliker's Zeitschrift, 1849. 694 THE cell: the nerve-tubes, either by the latter joining on to the nucleus or to the caudations of the former.* I will add, that such is also the conclusion at which Professor Wyman,! of Cambridge, has arrived, from his researches into the nervous system of the Batrachians, and in which the above point received a special consideration.! Such are some of the historical relations of the nervous tissue, by the keeping in mind of which we shall the better understand its pre- sent condition, both as regards structure and function. At present, we recognize this tissue as consisting of two elements — nerve-cells (including, of course, ganglionic vesicles), and nerve- tubes. The former is the true histological element, and out of which the latter is only a metamorphosed form. The genesis of each, ac- cording to my own observations, now engages our attention. The formation of the nerve-cells occurs quite early in foetal life. At first, the whole tissue, whatever is to be its subsequent condition, consists of cells. These are nucleated, and have an exceedingly delicate membrane, inside of which there are generally fine granules. In Mammalia, they are of about 1-2000 of an inch in diameter. Whe- ther they are the vitelline cells metamorphosed, or whether they are new formations from the beginning, out of these last, my own observ- ations do not allow me a decided opinion, for I have never been able to examine sufficiently young embryos in a satisfactory manner. I am inclined, however, with Valentin, § to the latter opinion.|| * It is true, that I have not repeated the observations of Wagner upon cartilaginous fishes ; and from the full statements of so excellent an observer as KoDiker in the affirmative, the question is indeed an open one; see his Mikroscop. Anat. Bd. ii. p. 390, et aeq. ■\ Anatomy of the Nervous System of Rana pipiens.— Smithsonian Contributions to Knowledge, Washington, 1853. % For additional -writings on the relation of the ganglionic globules to the nerve- tubes, see especially Hannover (Recherch. microsc. sur le Syst. Nerv. 1844, p. 69, pi. viii. where he has described and figured them from Helix and Limax) ; Helmholtz (De fabric. Syst. nerv. evertebrat. p. 10), and Will (Muller's Arch. 1844, p. 76). Han- nover is quite in favour of the view of their direct material connection. See also Muller's Physiology, Jourdan's French Translat. LittriS's Edit. Paris, 1851, vol. i. p. 560, where the direct connection of the ganglionic globules and the fibres is urged with considerable weight. See also a review by me, of Prof. Wymau's work above quoted, in SiUiman's Journal, Sept. 1858, where this subject is touched upon, and its historical relations given. § Valentin; loc. ciiai. Entwickelungsgeschiohte, &c. p. 183. II As to the genesis of the ganglionic vesicles or cells, it is the same as that of the common ceUs. As I have before remarked, they are these last in a hypertrophied condition. This opinion is founded upon the fact that I have traced them, in point of ITS PHYSIOLOGY AND PATHOLOGY. 695 These primitive nerve-cells have a remarkably uniform aspect, and are generally situated in a light gray, punctiform blastema. In the Fig. 13. Nerre-cells ; their transition into tubes, and the appearance of the nerve-tuhea of the cerebrospinal system. The first three figures from, brain and spinal cord of foetal goat of 14 days; the remaining ones from nervous system of tadpole. «. Nerve-cells from brain of fcctal goat, their formation occurring accord- ing to " my own mode." 6. The same, from spinal cord,,beginning to arrange themselves in a linear man- ner; b's caudate cells, c. Still farther arranged, and tubes appearing, d. Tubes formed ; the nuclei of the old cells remainii^ in the walls, k. A nerve-tube from a spinal nerve, without double contour. /. Nerve-tubes from same, with double contour. B. Axis-cylinder. J". White substance of Schwann, g. Globular and cell-like forms assumed by expressed portions of axis cylinder. embryo of a goat, half an inch in length and fifteen days old, these cells had already formed in that part which was to be the size, all the way from the former to the largest of the latter. But as to the point ■whether am/ cell may attain this development, or whether it is the peculiar destiny of &few, I cannot say. 696 THE cell: cerebrum. In the spinal cord, they had just passed on to the con- dition of fibres ; still, they had left their marks behind, and it was easy to perceive the phases of the change. It would appear that the first step of this fibre-change is a partial arrangement of these primi- tive cells in a line or series. Then their delicate walls coalesce, and a continuous tube is formed, the nuclei of the component cells still persisting. At first, this tube has a most delicate appearance, but afterwards it may assume a more opaque aspect by the appearance of granules on the wall. I have said that this tube is formed by the coalescing of the walls, but, as far as my own observation goes, this is a point which has not been demonstrated. On many accounts, it is a matter of just infer- ence ; but I have often thought that it might well be formed by a plasmatic membrane, enveloping a row of cells lying contiguous, or nearly so, to each other. At any rate, the persistence of the nuclei in their walls, for a brief period after their formation, shows their cell-origin. It would appear that, subsequently, these nuclei disap- pear for the most part, and there is then left a delicate tube with transparent contents. The double contour of this tube is due with- out doubt to the portion of the contained liquid lying next to the sheath, becoming more opaque than the rest, producing the " white substance of Schwann." When the liquid contents of these tubes escape, they very naturally assume a globular form, and their ex- terior portion in contact with the surrounding liquid in which they float becomes coagulated, and the whole retains its original form. Afterwards, a coagulation of that portion of the liquid of these globules lying next to the periphery may occur, and so these globules may have a double contour as well as the nerve-tubes themselves. The diameter of these primitive tubes, thus formed, is probably about that of the primitive cells ; but after manipulation, however careful one may be, there appears to be a deviation from their origi- nal aspect. The fluid contents of the tubes escape either partially or wholly— in the former case, giving it a very irregular appearance, and in the latter, allowing the membranous sides to lie against each other, giving it more the aspect of a delicate thread. But I cannot think that these last delicate thread-like fibres are ever formed as such from the beginning, or, as Remak has supposed, that they are the " earlier forms" of the larger fibres. The notions entertained by some of the earlier microscopists, that these tubes formed a cir- culating system, arose from the globular forms which the contents of these tubes often assumed, exactly as would occur if they had ITS PHYSIOLOGY AND PATHOLOGY. 697 made their escape. I scarcely need say, therefore, that all such appearances are artificial. As I have already remarked, it was the opinion of Valentin, for- merly, that these delicate tuhes are the sheaths proper of other tubes of a more opaque character. This opinion has since been clearly shown to be erroneous, and I may add, that what I have recently seen, in my own observations, is to the same effect. Thus, in the gradual development of the nervous system in the tadpole, you have first the primitive cells, and then, in the midst of these, and by changes just described, appear these delicate tubes, without the in- tervention of any other. Such are the phases of genesis of the primitive nerve-cells, and their transformation into the white nervous fibres, as I have traced them in foetal life. As for another set of fibres, found and described by Remak — the gray or so-called organic ones — they need not here detain us long. In showing what they are I cannot do better than to quote the words of Remak,* who was among the first to study them. He says : " They are not tubular, that is, surrounded with a sheath, but naked, being transparent, almost gelatinous, and much more minute than most of tlje primitive tubes. They almost always exhibit longitudinal lines upon their surface, and readily separate into very minute fibres. In their course, they are frequently furnished with oval nodules, and covered with certain small oval or round, more rarely irregular, cor- puscles, which exhibit one or more nuclei, and in size almost equal the nuclei of the ganglion globules." The opinion of Miiller,t who followed Remak, is to the same effect. With such a description, they would certainly seem to be entitled to the name of a distinct set of fibres. Moreover, they are found in the nervous system of organic life in the ganglia. But within a few years doubts have been raised as to the nature of these fibres as thus described ; and there are good reasons for now believing that they are rather a form of simple fibrous tissue than true fibres of nerve. I do not propose to discuss the matter here, for I have not investi- gated to that extent, some of its points, that I should wish to do. But, as yet, my opinion coincides with that of Henle, who regards the common gray nerves as only solid cords of nervous fibres like those * Remak ; loc. citat. 1838, p. 5. f MiiUer ; Physiologie du Systbme Nerveux, &c. trad, par Jourdain, Paris, 1846, torn. i. p. 126. VOL. VI. — 45 698 THE cell: belonging to animal life, and therefore that the fibres noticed by Kemak and others belong to a different tissue. Such, at least, is what I should deduce from my own limited observations ; and as such, the genesis of these bundles of primitive fibres would be the same as that of the same fibres in an isolated condition. But besides the true nerve-fibres (if I may thus designate them) and those reputed ones of Remak and Miiller, there exists another set, found in the ganglia of the sympathetic system ; but they are not pe- culiar to it alone, for they also occur, but more rarely, in the cerebro- spinal tissue. They are distinguished from the first by their smaller size (being about one-third), and their even, smooth appearance, hav- ing all the aspect of a small tube filled with homogeneous minutely granular matter ; moreover, they want the double contour of the former. These may be called the organic nerves, and this in con- tradistinction to those fibres of Remak, or those bundles of ordinary nerve-&avGS, which apparently constitute the gray nerves, and which are only a conventional aggregation of the common nerve-tubes.* The genesis of these organic nerves takes place, according to my own observations, in very much the same way as that of the others we have just described. There is this difiierence, however, that in the common nerve-fibres there appears to be a kind of liquefaction or clearing up of the contents of the cells after they have united to form the tube ; and this produces that glass-like transparency for which they are noted. But in the organic fibres, the cell-contents remain, * A few years since, the questionwliether or not there really existed a set of fibres peculiar to the sympathetic system, was discussed by some of the continental ob- servers. The conclusion at which they arrived is as I have stated above, viz., that the gelatinous fibres of Eemak and Miiller are not nerve-fibres, but that the nerve- fibres peculiar to the sympathetic system, or nearly so, are such as those of which I have just given the description. See Kolliker, Die Selbstandigkeit und Abhandigkeit des Sympathischen Nerven- systems, an abstract of which is in Mr. Paget's Eeport on Anat. and Physiology, Brit, and For. Med. Rev. July, 1846. After all, there is some obscurity about the matter, if we take Remak's statement; for he says that the fibres described by him are much smaller than the primitive nerve-tubes. In this respect they would correspond to the true orgamo fibres I have just described. But in aU other particulars they do not agree. Is it not probable that Remak is mistaken in his idea of their size ? For some special details on this subject, see Kolliker, Mikroskop. Anat. ii. p. 528, and Miiller's Physiology, transl. by Jourdain, 2d ed. by Littre, Paris, 1851, vol. i. p. 563. This is a point which studies on the lower animals will tend much to elucidate ; and see the vrritings of Leydig in Siebold and Kolliker's Zeitsch. f. Wissensoh. ZooL passim. ITS PHYSIOLOGY AND PATHOLOGY. 699 the nuclei are partially persistent, and therefore the tube presents a grayish-white homogeneous aspect. The figures which Schwann has given correspond quite closely with what I have observed. Such are the more general genetic relations of the nervous tissue in both its elementary and compound conditions. As I have before remarked, the greatest uniformity throughout the animal kingdom exists. It is true that among some of the invertebrates the nerve- tubes may not have the same aspect, but homologically they are the same, arising from cells which everywhere have not only an identity of function, but of aspect also.* Fig. 14. Gray or gelatinous nerve-tubes, from sympathetic system of a snake (HeUrodon Platyrrhinos). The presence of nuclei in the tubes shows clearly their cell-origin. Compare the figures I have given with those of Schwann-f (Magnified 350 diameters.) rv. Muscle-cells and Muscular Tissue. This tissue has a universality second only to the one we have just been considering, and like it, also, has an homologous structure wherever occurring. But, besides these similarities, there is another, an histological one, and which did not escape the penetrating mind of Schwann. So that it may be said that the muscular and nervous tissues resemble each other in nearly every point of view more closely than any others in the economy. They are properly, there- fore, considered in succession. But we will first refer to its history and criticism, which will enable us the better to appreciate some of its important bearings. * With some of the Acalephse, the nervous tissue consists of cells only, and instead of nerre-tubes there are beaded rows of cells — an illustrative histological point. See Agassiz, Mem. Amer. Acad. iv. 1850, p. 232. + Loc. cit. Syd. Soc. ed. pi. iv. fig. 8. 700 THE cell: And in so doing, I cannot pretend to take up a retrospective view of it in all its common histological relations, for these would be of but little interest. But its history and criticism, as a eell-tissuB, is what concerns us. This, of course, does not date back farther than the time of those numerous and valuable histological researches which just preceded the ever-memorable labours of Schwann. Krause* recognized that the primitive fibres were composed of a series of globules. The nature of these, however, he did not fully understand, and the same is true of other investigators of that time ; but as clear ideas of its essential structure could only be founded upon a knowledge of its developments, Valentinf appears to have been the first who studied this tissue in an intelligent manner. He recognized the primitive fibre-cells in the ovum, and their successive metamorphoses until the formation of the fibre itself; also the arrangement of the granules, until, he says, they appeared like a string of pearls. In fact, Valentin appears to have proceeded as far in these studies as he well could, considering that he did not then recognize the grand laws of cells which were soon to be brought out by Schwann. Schwann combined the labours of those who preceded him with his own, and thereby the force of the problem of the genesis of a tissue which remains so short a time in its cell condition, was solved. He pointed out its necessary cell-origin, and the phases which, from this last fact, it would pursue. These facts could not be better established, and I am not aware that any advance has since been made.| The researches soon to follow could be little else than confirmatory of these first, or such as would relate to its function and mode of opera- tion. This last (the modus operandi) required studies as to its granular * Krause; Handbuch der Menechlichen Anatomie, Hanover, 1833, p. 57. Another edition of this appeared in 1841. •f- Valentin ; loc. citat. Entwickelungsgeschichte, p. 268. J It may be well to allude to the opinions of Valentin on the genesis of this tissue, and which have been published subsequent to the work quoted above. He thinks that in the interior of the tube produced by the fusion of the cells, there is a central cavity, which remains throughout life. This cavity at first contains the nuclei of the cells in- closed, but after the absorption of these, it is filled with a gelatinous liquid. Between this central cavity and the waU of the tube, are developed the fibrillse around the nu- clei of the cells (what cells ?), their increase in number going on at the expense of the cavity. These fibrillss at first are pellucid, but afterwards become granular, and sud- denly assume a striated aspect. Vide Berlin Encyolop. vol. xxiv. 1840, p. 212; and MuUer's Archiv, 1840, p. 204. I scarcely need say that Bowman's results have shown tlie erroneousness of tiis view. ITS PHYSIOLOGY AND PATHOLOGY. 701 constituency, or the arrangement of the granules in the interior of these primitive cells thus coalesced, giving rise to the striated aspect. In 1840, Mr. Bowman* published his comprehensive memoir, in which the whole subject was most ably treated, and the paper has since been one of reference in this and other languages. Bowman showed that the elementary structure of the muscle is such, that it is not only capable of being divided lengthwise, thereby forming threads, but also cross- wise, forming disks — thus showing that it is composed of particles of equal size, united and arranged in two directions, each one standing equidistant from the surrounding neighbouring ones. This view, suffi- ciently substantiated by the care of the author's (Mr. Bowman's) own researches, has been since confirmed by many good Microscopists. But a corresponding view which it involved, has not been so satisfac- torily made out. This was the view that each of these particles was a cell, and therefore that the whole muscle was only a bundle of small cells, arranged after a regular manner. This view was advanced by Drs. Carpenterf and Sharpey,{ and is based upon appearances they have witnessed upon prepared specimens. As I have just stated, this point has not been equally clear to others ; and, in my opinion, as I shall soon show, it is rather a forced interpretation of appear- ances. When a subject had been so thoroughly wrought out, as this had, in its earlier years, it cannot be strange that recent times have not much advanced its condition. And so, since the memoir of Bowman, I do not think that much has been done to change the face of the matter. To be sure, much has been written upon debatable points, and to show that optical illusions have' often been mistaken for real appearances. The Qomp, Hendus, of 1847, contains several memoirs upon this subject, and especially that of Prevost, in which the genesis of this tissue, with many peculiarities, is traced over a wide range of ma- terial. But, by far the most comprehensive work in this direction, of late years, and in which the finer and more delicate points are wrought out with the improved means we now possess, is the memoir of Le- * Bowman; Philosoph. Transact. 1840. f Carpenter; A Manual, or Elements of Physiology, &c. London, 1846. Also, his other more recent physiological works. J Sharpey ; Human Anatomy. By B. Quain. Edited by Wm. Sharpey. Second edition, London, 1846. 702 THE cell: bert.* And I am happy in saying that subsequent investigations of my own have elicited the same results ; and I place the more re- liance upon these, since drawings which I made, before the work of Lebert was accessible to me, correspond quite closely with these last. But however accurate and careful may have been the researches of Lebert, they have a conformatory, rather than an original value, and may be regarded as bringing to the test and showing the truth of the earlier opinions of Valentin and Schwann. f What these were, may be learned from a description of what I have wrought out for myself, and which will now engage our at- tention. If we confined our range of study of this tissue to the higher ani- mals, in which it can scarcely be said to exist at all, except in an ulterior condition, our knowledge of it would be imperfect. We shall do well, therefore, to commence with the lower forms in which it per- sists in its very earliest stages, that of eels, and as such performs its functions. We find it in this condition in some of the Kadiata. Such is the muscular tissue of the pedicle of the attached medusa-form of Tuhullaria, and, when examined, will be found to consist of cells ar- ranged in a linear series. When the pedicle is in a state of relaxa- tion, these cells are spherical, and are filled with granules. The contraction results from simultaneously becoming flattened, or disk- shaped' — their long diameter being at right angles with the way of contraction. Here you have motion due to the direct agency of cells ; in other words, the simplest form of active muscular tissue which is of cell- origin. But a muscular or motor tissue may be even more sim- ple than this. In the instance just cited, we have seen that the cells were filled with granules ; and I am convinced that to move- * Lebert; Annal. des Soi. Nat. 1849, et Mai, 1850. t The following are the names of some papers on the genesis and intimate character of the muscular system, -which have appeared within a few years : StanniuB ; MuUer's Archiv, 1847, p. 440. Cramer ; Guy's Hospital Reports, vol. vi. part i. Dobie ; Annals of Nat. History, Feb. 1849. Lebert; Comp. Kendus de la Soc. de Biologie. Paris, 1849, p. 76. For the Histology, Anatomy, &c. of the Muscular System in aU the classes of the animal kingdom, with many interesting details, see Comparative Anatomy by Siebold and Stannius, trans. &c. by Burnett, under the head Muscular System of each class. See, also, several anatomical and physiological text-books, especiaUy those of Car- penter, Sharpey's edition of Quain, Kirkes and Paget, and Jourdain's translation into French of Muller. ITS PHYSIOLOGY AND PATHOLOGY. 703 ments of these last is due the change of form in the cell, producing contraction. By a kind of mutual attraction which they take on, they become more closely aggregated ; a decrease of space is the result, 'and the cell-membrane containing them follows their move- ments, and at the same time brings their lever to produce the second- ary results. It is therefore evident that the movements of these granules do not depend upon their being enveloped by a membrane, although the possession of this may increase the definite character of the motion. Fig. 15. The ceZZ-muscle of the pedicle of the attached medusarform of TuhvJkiria (nov. 8p.)> showing the con" traction due to cells, a. Natural relaxed state. 6. The state of contraction by flattening of cells. This even more simple form of tissue to which I have alluded, is found in many Bryozoa, and in the integument of many Entozoa, and especially of the class Nematoidea. It consists of a collection of granules, which are not allocated by an investment of cell-membrane. In the genus Alcyonella of the Bryozoa, if the muscle which moves one of the tentacles be examined, it will be found of a fusiform shape, and consisting only of a sac of that form, containing these primitive granules ; and, as I have repeatedly watched it, the contraction takes place sequent upon a mutual attraction of these granules, by which they occupy a less space. We can conceive of no motion simpler than this, and this may be taken as the ultimate expression of muscular movement, divested of those levers and other means for the increase of power which belong to the compound forms of this tissue, giving it, in fact, its peculiar composition. But let it be remembered that in this mutual attrac- tion of these primitive granules lies all muscular contraction, whether it he in the lowest or highest forms. As we advance into higher forms, we perceive that not only has 704 THE cell: this tissue advanced to the condition of being definitely arranged and allocated by cell-membranes, but these have coalesced so as to form tubes, as is the case with the muscles of organic life; but in the muscles of animal life, in which this tissue has reached its highest stages of metamorphosis, there is a step in advance of this; fox, not only have the cells coalesced into tubes, but their contents, the granules, have become definitely arranged, giving rise to the striated aspect. , Fig. 16. The tentacular piuscle of McyamHa (dot. sp.), being composed of a fusiform sac filled with granules. a. Natural or rela.xed state. &. State of contraction. We will now look to the phases of this muscle formation. In the young embryo, nucleated cells are seen in those localities where the muscular tissue is to appear. I think, with Valentin, that these are formed from the vitelline substance, and are not metamorphosed vitelline cells ; at any rate, they are not easily distinguished from those about them which are to form other tissues, if we except their little larger size. Their first change towards a condition of organization above that of cells, consists in their tendency to be arranged in a linear series, or rows. There then appear rows of nucleated cells, having granular contents; next, these cells coalesce and form tubes, at the same time their contents becoming more tho- roughly granular. There are, then, at this stage, tubes with homo- geneous granular contents, with the nuclei of the component cells still persistent. It is on this stage of development that the fibres of the organic muscles rest, and the above, therefore, constitutes their de- scription. The development still continuing, these fibres, thus formed, increase in size by interstitial deposition of granular matter ; at the same time the nuclei, and other remains of their cell origin, for the most part disappear. Then the granules, thus accumulated, begin to be grouped ITS PHYSIOLOGY AND PATHOLOaY. 705 in a regular manner, and when this has been accomplished, the ■whole presents a very uniform, regular aspect, constituting the true striated muscular fibre ; but, when fully formed, it is only in those belonging to the lower animals that any traces of the original cell- structure can be perceived. Certainly, in Mammalia, there is no trace left that can be perceived in the normal state. Still, how- ever highly metamorphosed, this tissue does not lose its original cell- traces. For, in a condition of it produced by defective nutrition, and which may be properly termed retrograde metamorphosis, con- sisting in the unravelling of its structure, the marks of the old cells are seen ; exactly, if I may use the comparison, as when a house goes to decay, its finish is stripped off, and you see, what was before hid- den, that the rafters and beams have composed its real structure. There is another appearance which is sometimes seen, and which, as it shows beautifully how the traces of the ancient cells perish, may well be mentioned here. I refer to the plication of the fibre often observed in specimens of boiled beef. It is plicated or folded upon itself. But this plication takes place at the weakest point, which is at the union of the old cells with each other. Therefore, the length of each plication should be that of the primitive muscle-cell ; and in a Fig. 17. Muscular fibre and ita formation ; from very young tadpole. «. Muscle-cells as they exist in the em- bryo. 6. The same, linearly arranged, c. CoaleBcing and forming a cylinder, d. Cells completely fused, but nuclei still persistent, the granular matter unarranged constituting the muscular fibre of organic life. c. Still farther progressed, the granules definitely arranged forming sinffi, hut nuclei visible here and there, constituting the muscular fibre of animal life. /. A plicated muscular fibre of boiled beef, the plication taking place at the junction cf the ancient cells. The appearances of muscular fibre of the higher animals, and in whidi no nuclei are visible, I do not figure, for any one can easily see it. I have given only its histology. 706 THE cell: specimen which I recently saw, and made the measurements, I found this to be correct.* It will be seen by the above description that the muscular fihre, and not the fihrilla, is the true embryological cell-element, the pro- duction of the fihrillee being an artificial division, exactly as is the transverse cleavage. Moreover, it will be seen that the beaded cha- racter of this fihrilla is due to a regular arrangement of granules, rather than to a longitudinal series of cells. In the formation of the fibre and its development, as its increase takes place by interstitial growth or the internal deposition of gra- nules, it would follow that those of the embryo would be much smaller than those of the adult. That this was really so, was made out by Harting,f some time since, from comparisons he instituted between the fibres of embryos and their adults. Recently, however, I have had occasion to arrive at the same result. The muscular fibres of the gluteus maximus of a goat of two months (the natural term is five months) I found to be only one-fourth the size of those of the adult. From the phases of development, as I have just described them, of the two kinds of muscular fibre, viz., animal and organic, it would follow that the size of the latter should be much less than that of the former ; in fact, it ought to be exactly what the former is before the changes for striation take place, or as it is in the embryo. Such, indeed, it is in man and Mammalia, as far as my observation goes — being about three or four times smaller. Fig. 18. m 1 M Muscular fibres of a foetal goat of two months, from gluteus maximus, showing relative size with that of the adult, a. Muscular fibres from gluteus maximus of foetus. Size, 1-1800. b. Muscular fibres ftom the same of adult. Size, 1-500. (Magnified 350 diameters.) The fact of the fibres in the adult being so much larger than those in the embryo, may explain how the increase of the muscular tissue, * Henle gives a figure of tlie same appearance. Vide TraitiS d'Anat. g^u&ale, &o. pi. iv. fig. 4, F. t Harting ; quoted in M. Paget'a Report on Anatomy and Physiology. Brit, and For. Med. Rev. April, 1846. ITS PHTSIOLOGT AND PATHOLOGY. 707 as a -whole, takes place, either from the natural growth of the body, or from continued exercise. For, as there is no evidence that mus- cular tissue is developed de novo except in the embryo, the increase in size, for instance of the Sleeps and triceps of the arm, after exer- cise, is due to the interstitial growth of fibres, which from disuse have hitherto remained in their embryonic condition. As the subject of muscular tissue will not again come up in this work, its function being too evident to be separately discussed in a following chapter devoted to function, I may properly here notice another point of much interest and importance. I refer to the dependent relations existing between the nervous and muscular tissues. As is well known, it was the opinion brought forward by Haller, that the muscular tissue had an inherent contractility, aside from any influence of the nervous system. Subsequently, however, this view was disputed, it being argued that, in the cases in which detached portions of this tissue exhibited contractile movements, these were due to the presence of a small bit of nerve in them, and which was the agent of the action. Within a few years, how- ever, and since investigations of this kind have been more minute, and extended to the lower animals, phenomena have been seen jus- tifying the view of Haller, although based upon different and much more scientific data. The nerves, in their distribution in the mus- cular tissue, do not enter the fibres themselves, but form anastomoses on their surface. If, therefore, isolated fibres can be seen, in the field of the microscope, to contract and relax, it is evident that such Fig. 19. Muscular fibre-cells, ad. nat. del., from human spleen. 708 THE cell: motion cannot be due to nervous influence (for there are no nerves), but rather to the inherent power of the tissue itself. This was seen some time since by Mr. Bowman,* and more recently by Professor B. Weber ;t and still later, I have had the good for- tune to observe it several times while making some researches upon the viscera of insects; and, as I had in my memory the observations of the two above-named observers, I watched it carefully, and was quite satisfied that it thus occurred. Fig. 20. Muscular fibre-cells from the iris. Copied from Lister's paper.' Moreover, in the muscular tissue of Tuhullaria above mentioned, the contraction can be distinctly observed to take place through the agency of the cells and their contents ; there positively being no nervous filaments whatever entering the organs. As physiologists, we may with candour ask, why should .not simple cells or utricles have this power instead of its being entirely refera- ble to a production of cells in the brain or nervous system ? We can as well conceive of a muscle-cell having this power as a brain-cell. It is true, however, that in the more important adaptive motions of life, there is necessarily presupposed a unity of power under the guidance of volition or its equivalent.^ * BoTnnan ; loc. cit. Phil. Trans. 1840. j- Weber; Arobiv d'Anat. g^n^rale, JanT. 1846. t In ftie preceding account, I hare made no allusion to a peculiar celloid tissue, ITS PHYSIOLOGT AND PATHOLOGY. 709 V. Fibre-cells and Fibrous Tissue. Under this head, I include all those forms of tissue commonly known by the names of cellular and areolar ; for microscopy has wonderfully simplified our knowledge of its characters. It is true that the relations it sustains in the economy are mostly those of a mechanical nature, and on this account it might seem proper that its consideration should be omitted. But then, again, owing to its very simple character, its presence is almost universal, and of all the tissues, it is the one most easily and rapidly reproduced. On a future page, we shall learn that its pathological relations are of the most important character, and for this reason alone, if not for others, it should here be considered in its normal histological conditions. Functionally, full as much as structurally, it is allied to the mus- cular tissue last considered, and in some instances it assumes the active conditions of the latter in a very imperfect manner. I have, therefore, taken it up in this connection. We will first refer to its history and criticism, brief though it may be. Although Leeuwenhoek, Malpighi, and other of the older anato- mists were well acquainted with the common anatomical relations of this tissue, which, from its mechanical importance, they studied well, yet its histological characteristics cannot be said to have been learned -until a much later period, and when better means of investigation came into use. This was not before 1833. At about, or soon after, found in various parts of the body, and now pretty clearly shown to be of a muscular nature. The tissue here alluded to is found in parts possessing contractile properties, but which contain nothing like ordinary muscle. It is made up of long, large, nucleated, queer-looking fibres, the uncouth remains eyidently of the characteristic muscle-cells. Their histological and local peculiarities have been pretty thoroughly worked out by KolUker (Zeitsoh. f. wissenschafl. Zool. i. Abth. 1, 1848). He has shown that the muscles hitherto regarded as composed of "smooth fibres," are really made up of elongated cells with an oblong nucleus, which he calls "muscular-fibre cells." He has found them in the nipple and its areola, in the -dermis, Crampton's muscle, the digestive canal, the bladder, in a part of the prostate and vagina, the arteries, the veins and lymphatics, the ureter, the urethra, the Fallopian tube, the uterus, the dartos, the vasa deferentia, the trachea and bronchia, the spleen, and many other organs. See Comp. Rend, de la Soc. de Biologic, 1849, p. 156 ; and art. Spleen, in Todd's Cyclopsedia of Anatomy and Physiology. The composition of the iris is of the same fibres. See a paper by Lister, Quarterly Joum. of Micr. Sc. No. I. Oct. 1862. For the comparative histology of the muscular tissue, with many interesting details in every class of the animal kingdom, see Comparative Anatomy by Siebold and Stannius, trans, from the German, &o. &c. by Burnett, under head Muscular System, passim. 710 THE cell: this time, a number of microscopists published accounts of its ulti- mate structure. Among these may be mentioned the names of Krause,* Wagner,t and Valentin.J Each and all recognized that it was composed of fibrillae which were formed by the alteration of cells. The subsequent labours of Eulenberg§ and Gurlt|| made these points the more clear. I need not here point out the distinctions and differences they made out. Soon afterward, Schwann gave an indi- viduality to the whole, by referring its genesis necessarily to cells. Its formation, in all its phases, he has pretty clearly indicated ; and, although on some minor points he may not have been fully correct (at least, according to more recent researches), yet the general out- line of the genesis was fully made out. He showed the existence of the two kinds of fibres, the yellow and \the white; the former existing alone in ligaments, tendons, aponeu- roses, &c., the latter in the middle coat of arteries, ligamentum nuchas, &c. ; but both kinds are present in the areolar tissue generally* Since Schwann, the labours of Gerber,Tf Henle,** and Todd and Bowmanft among others, have increased our knowledge of its more minute details, its functional and other characteristics ; but I am not aware that they have changed materially its aspect in an histological or genetic point of view. More recently, however, than these writers, this tissue has been the subject of interesting inquiries, as to its purely mechanical rela^ tions in the economy, as occurring in some localities ; as, for instance, in the skin and dartos, where it has an irritability and power of con- traction. This is undoubtedly due to nervous influence of a reflex character. And it may well be questioned if the fibres thus capable belong to the fibrous tissue, and are not rather a low form of unstri- ated muscular fibre, being intermediate between the muscular and fibrous tissues. In my opinion, such is the true state of the case, and it may serve to explain the fact that, in some instances, true muscular fibres * Krause; loc. cit. 1833, vol. i. p. 13. f Wagner ; LekrlDuch der vergleioliende Anatomie, 1834, p. 61. t Valentin ; Ueber den Verlauf und die Enden der Nerven, Bonn, 1836. J Eulenberg ; De Tela elastioa, Berlin, 1836. II Qurlt ; Lehrbuoh der Vergleiohenden Physiologie des Haussaengetheire, Berlin, 1837, p. 19. 1[ Gerber ; Handbuch der allgemeinen Anatomie, &o. Berne, 1840, p. 134. ** Henle ; TraitiS d' Anat. g6n(5rale, &o. torn. i. p. 374. tf Todd and Bowman ; Physiological Anatomy. ITS PHYSIOLOGY AND PATHOLOGY. 711 have been thus found.* The true fibrous tissue, therefore, has no immediate connection with the nerves, and sustains merely mecha- nical relations. We will now refer to its genesis as based upon my own observa- tions. On some account there may be a propriety of dividing this tissue into several varieties as Schwann and Henle have done, but certain it is that it is composed of two elements only, wherever found. These are what have been well designated as the white and yellow fibres. The former consist of inelastic bands of a very variable size, and present markings with their long diameter. This lining, however, does not indicate a finer subdivision, for the fibre cannot be split up into fibrillae. These fibres, apparently thus composed, present often a wavy as- pect ; thereby allowing of some extension and retraction. Such is the element of which the tendons, ligaments, aponeuroses, fibrous mem- branes, &c., not to mention the pathological products, are composed. It is emphatically a cell product, and the phases of formation can be easily watched. First, you have round or oval nucleated cells ; these become fusiform, or lengthen at both ends, their liquid contents be- coming more opaque. In this state, they become united together in a serial manner, not so much by a coalescence of the contiguous walls as by a joining together through the intervention of a plas- matic blastema. Thus formed together, the nuclei remain for some time, and there is an irregular splitting up of the old cell into finer fibres, though not of a uniform character. These formative cells not having a proper individuality, at least as to size, the fibres formed from them have a variable dimension ; some of the larger ones have a size of 1-500, and the smaller ones of 1-2000 of an inch in diameter. This splitting up of the cell, to which I have just alluded, appears always to take place from its periphery towards its centre ; so that, in the process, you first perceive that the elongated cell is bifid or trifid, &c., this extending more or less its whole length. The phases of formation thus described can be traced in the embryo, or perhaps full as well in the pathological products of a fibrous cha- racter, in which this tissue persists on its embryonic stage. The yellow fibres may, as Schwann has said, be regarded as distinct in their character and formation. They consist of long smooth fibres, curled upon each other when no extension is made. Their size, like that * See Comp. Rend, des Stances de la Soo. de Biologie, a Paris, 1850, p. 38. 712 THE CELL: of the other variety, is variable, being between 1-3000 to 1-7000 of an inch in diameter. Their locality is in the middle coat of the arteries,* Fig. 21. White fibrous tissue and its formation, from a tendon, a. Pibre-cells in tlieir early stages of growth, b, XTnited into a cylinder and split longitudinally, the nuclei still seen. c. A representation of the filaments separated &om the fibres — their coiling, twisted aspect. (Magnified 250 diameters.) the chordae vocales,the ligamentum nuchse, and the ligamenta subflava, besides being combined with the white fibres in various parts. f The mode of genesis of this tissue has been a point upon which diflferent physiologists have expressed dissimilar opinions. SchwannJ speaks of having examined the ligamentum nuchse of a foetal sheep, which he found composed of longitudinal fibres containing nuclei of cells. He therefore infers their formation by the coalescence of cells, as is true of the other variety. But, according to his own account, his observations were not complete or fully satisfactory. The opinion of Valentin§ is quite difierent, for he thinks they are formed by the apposition of matter around fibres which are formed by the coales- cence of cells. Henlell regards them as formations from the nucleus, or, as he would call them, nuclear-fibres ; exactly as are formed many fibres found in vegetable tissues. He, however, bases his opinion more upon ana- * Henle thinks that the elastic tissue of the middle coat of the arteries is different from that of the ligamentum nuchse, &c. ( Vide TraitiS d'Anat. g6n. torn. i. p. 440.) But this difference may he a local iastead of an histological one. t For an account of the localities of this tissue, vide Eulenberg ; loc. citat. p. 13. J Schwann; loc. citat p. 151. I Valentin; Miiller's Archiv, 1840, p. 216. II Henle ; Trait6 d'Anat. g&uivale, &o. torn. i. p. 487. ITS PHYSIOLOGY AND PATHOLOGY. 713 logy than upon real observation. It is true, as he observes, that, be- cause they do not appear affected by acetic acid, and, under any treat- ment, show no unequivocal nuclei, they resemble nuclear formations. But this does not prove them to be such, although it would certainly seem to show that they are not of direct cell-membranic origin. My own investigations have been made upon the ligamentum nuchse of foetal and adult goats. This tissue seems to make its appearance at a very early period. In a foetal goat of 21 days, its existence was marked by the appear- ance of long and delicate fibrillse having a diameter of 1-25,000 of an inch. These were most probably formed by the linear aggrega- tion of granules or utricles, as I have described on a preceding page. It did not appear to me, therefore, that they had a cell origin, as is true of the white fibrous tissue. ,Fig. 22. Yellow Eihroua Tissue and its rormation. a. Fibrillse from ligamentum nuch» of a foetal goat of 21 days; size, 1-25,000. 6. Same, from the same locality, of a foetal goat of four months, c. Fibrillse of tissue in its adult form ; size, 1-3500. In a foetus of the same animal, of four months (that is, one month before birth), this tissue was still of a grayish-white aspect, and the fibres were about 1-9000 of an inch in diameter, having the aspect of threads, and revealing no farther structure after the action of acetic acid. In the adult goat, they had a yellowish cast, and were of a diameter of about 1-3500 of an inch. Any treatment by the strongest acid showed no farther structure. VOL. VI. — 46 714 THE cell: From these facts, it would appear that the yellow fibrous^ tissue is not of cell origin, but is a form of fibrillated tissue, which in- creases regularly with the animal until it has attained its full size. In the new-born goat," it is nearly three times smaller than in the adult, and therefore resembles the gradual growth of the muscular fibres, of which I have spoken on a former page. VI. Adipose Cells and Adipose Tissue. This tissue is always found associated with the one last considered, and Schwann, in his chapter on areolar tissue, considered it as a part of it. In the present case, I have thought proper to take it up in a separate division, but in the close connection of succession. The adipose tissue is strictly a cellular one, although these cells are in- terwoven generally with the fibrous element which serves as its mechanical support. These cells are spherical when not subjected to pressure, have a smooth contour, although they soon lose it when removed from the body and placed in a lower temperature, for their oily contents contract by cold. Their size is very variable, some- times they are observed quite small (1-2000 of an inch), and then again they are so large as to be distinguished as glistening points by the naked eye. As usually seen, they appear as simple vesicles, filled with oil, and ' it is rare that any trace of a nucleus is seen. Fat-cells, therefore, cannot be said to be nucleated cells, whatever opinion may be enter- tained of their origin. This fact has given rise to some dispute as to their formation. The question is, are they to be regarded as cells having always a pre-existing nucleus, or are they vesicles, which may or may not contain nuclear matter. Valentin* has noticed their appearance in the human foetus (between the third and fourth month) in the palm of the hand ; he describes them as collections of little cell-like bodies, which also exist isolated from each other. But these facts throw no light upon their primitive formation, a point which, from direct observation, is not yet well made out. Schwann very naturally inferred their cell-origin according to the usual mode he described, and his opinion appears to have been con- firmed by the fact of recognizing in the walls of some a nuclear body. Henle'sf opinion is to the same effect. But the view which I am obliged to take, as based upon my own observations, is different ; it is, * Valentin ; loc. citat. Entwickelimgsgesoliichte, p. 271. f Henl(S ; Traits d'Anat. g^n. torn. 1. p. 424. ITS PHYSIOLOGY AND PATHOLOGY. 715 that they do not always form around a pre-existing nucleus, hut arise as simple vesicles. These vesicles are formed primarily, according to that method Ascherson* has pointed out, and to which the attention has heen called on a former page — simply hy the formation of a plastic membrane of albumen, around a minute globule of oil. This body then increases and dilates by the accumulation of oil within, ultimately producing the vesicle of a full-grown size. During this growth, nuclear bodies may form within, in the same way — by the union of oil and albumen. This is the reason why you sometimes meet with cells having, in their interior, one, two, three, or even more vesicles or nuclei ; or, there may be a single one of a well-marked character, having the aspect of a single nucleus. Such are the phe- nomena I have frequently met with, and especially in the formation of these cells in the mesentery of very young tadpoles. It is true that there are frequently seen whole groups of cells, in each of which is perceived a uniform nucleus. I therefore wish to be understood, that I do not deny that these bodies may exist as nucleated cells, but insist that they are often formed as simple vesicles. Fig. 23. Fat-cells and their formation, from bottom of orbit of eye of a dog. a. Vesicles without a nucleus, filled with fe,t. 6. Fat-cells fully formed, irregular in shape from pressure, and for the most part without a nucleus c. Two cells with traces of nucleus or granular matter adhering to membrane. (Magnified 250 diameters.) VII. The Caetilaginous and Osseous Tissues. I have thought best to consider these two tissues under a single head, because the one (the latter) can be regarded only as the other furnished with a mineral product, so combined with it, that the func- tions of organic shall be carried on in connection with the more me- chanical relations of inorganic life. We will, however, take them up separately, and that in the order in which they are produced. * Ascherson; Muller's ArcMv, 1840, p. 46. 716 THE CELL: In cartilage, we have a good example of the union of the simple, with the metamorphosed cell structure; the former being individual cells ; the latter, the fibrous tissue in its finer and coarser forms. A consideration then of this tissue, in connection with the fibrous one we have just passed, is quite proper ; and it will appear the more so, when we shall have shown that in some instances they pass imper- ceptibly into each other, and could not be distinguished, excepting for the simple cell element of the one, and the absence of it in the other. A review of the historical conditions of this subject as a whole, will well repay us, in rendering more clear some of the ob- scure points of the development and passage of the one into the other. As we have seen on a foregoing page, the history of the carti- ' laginous tissue as one composed of cells is intimately connected with the history of the development and nature of cells in general ; and in it, it may be said, the cell doctrines of animal tissues took their origin. It may, therefore, seem unnecessary to again pass over this field. But, in this connection, it is important as including the details of the subject. As Henle has justly remarked, it is quite singular that a structure so apparent as is this in most of its relations, should have remained so long imperfectly understood. For its study, in anything like a satisfactory manner, does not date back but a few years previous to the active labors of Valentin and Schwann. The older anatomists, who, in the historical accounts of the other tissues, seemed to have seized hold of points in a most wonderful manner, do not appear to have entertained very clear and correct ideas of its intimate anatomical and physiological conditions. The earlier labours of Weber* and Waguerf may be said to have laid the foundations of its more thorough study soon after. Others, it is true, and among whom may be mentioned Krause,J were labouring here at the same time. But in 1834, Purkinje,§ who has, as it were, identified himself with this structure and that of bone, published some observations which may truly be said to be the first embracing the histological features of this tissue, for he traced in it the early conditions of those corpuscles of bone now known under his name. * Weber; Meckel's Arehiv, 1827, p. 233. t Wagner ; Lelirbuch der vergleichenden Anatomie, Leipsig, 1884, p. 62. J Kvause ; Handbuoh der mensohliohen Anatomie, Hanover, 1833, bd. i. p. 48. ?i Purkinje and Deutoh; Depenitiori ossium struotura observatioues, Braelau, 1834. ITS PHTSIOLOSY AND PATHOLOGY. 717 In the following year, the work of Valentin,* so often alluded to, appeared, and in it were contained many valuable details. Valentin watched the appearance of this tissue or cells, in very young em- bryos. He recognized the cartilage-corpuscles, and the cavities in which they are formed, but did not agree with Purkinje, that the former were only early conditions of the osseous corpuscles. However, Valentin's opinions were well grounded in observations, and the interpretation of these last was as correct as well could be, considering the then existing ideas of the elementary forms of structure. Soon after this, came the observations of Miescher,t published with those of Miiller, which were remarkable for the care with which they were conducted, and the correctness of many of the views en- tertained. To Miescher is due the establishing of one point, viz : the necessary connection between cartilage and bone, the former as the invariable precedent of the latter. The same remarks, with but little alteration, will apply to the con- temporaneous work of Meckauer,! and all these may well be said to have paved the way for those labours of Schwann, upon which the whole grand idea of the cell was based. To what Schwann has done, it would be almost superfluous to allude. As far as regards the simple genesis, he did not, perhaps, advance farther than Valentin before him : but he traced out its phases as the basis of cell-doc- trines ; and on this account his observations on this tissue were much more numerous than upon any other. It is quite remarkable, how- ever, that this very kind of cell should also have been the one, the study of which lecl to the first doubts as to the universality of Schwann's and Schleiden's cell-doctrines. Since the work of Schwann, the labours in this direction have belonged for the most part to points other than those of its genesis, such as its nutrition, and its relations to the osseous tissue. In this connection may be mentioned the work of Henle,§ which will soon arrest our attention, when I speak of the history of bone-studies ; of Toynbee,|| devoted especially to the nutrition of cartilage, and then * Valentin ; loc. cit. EntwiokelungsgesoUchte, p. 26. •f- Miescher ; De inflammatione ossium eorumque anatomie generali. Acoedunt J. Muller's observationes de oanaliculis corpusoulorum ossium atque de modo, quo ter- rea materia in ossibus oontinetur. Berlin, 1836. J Meckauer; De penitiori cartilaginnm structura symbolse. Ereslau, 1836. I Henle; Traits de Anat. ggn&ale, &o. Trad, par Jourdain. Paris, 1843, tom. ii. chap. xiii. ^ II Toyubee ; Memoir on the non-vascular tissues. Philos. Trans. 1841. 718 THE cell: of Todd and Bowman,* — in which Mr. Toynbee's views of the genetic relations of this tissue and its transformations are embodied. In 1844, Valenciennesf published a memoir on the cartilage of the car- tilaginous Fishes, and the Mollusca. The subject received extensive attention, and, as I have since laboured some in the same field and met with similar results, I will state here the conclusions at which he arrives, although they have a more prominent zoological than histo- logical importance. " 1. That the cartilage-cells are generally ar- ranged in such regular plans that it would be possible to determine by microscopical examination the order or even the genus of the animal, from the character of its cartilage. 2. That none of the cartilage- cells have, in any species, canaliculi communicating with them; and, 3. That gelatine and not chondrin is abundant in the cartilages of cephalopods." Such results are of more importance than at first would be supposed. They relate to the condition of this tissue, as found in that class of animals resting on the lowest point of the ver- tebrated kingdom, and where it so persists on its embryonic type that we have a chance to study its peculiarities ; and, as will here- after be shown, our clearest views of the nature of ossification are derivable from allied though not from the same sources. Quite recently, there has appeared a very valuable paper on the formation of cartilage and its nutrition, by Dr. Leidy.J Of this paper it is hardly necessary for me to speak ; for, being wrought out with the characteristic care and elegance of the author, it has become well known to all familiar with this subject. Such are the prominent points in an historical retrospect of the cartilaginous tissue. It is now proper that our attention should be turned in a similar manner to one of its ulterior conditions, viz. that of bone, which need occupy us but for a brief period. Singular as it may seem, it was the opinion of some of the older anatomists, that bone was not formed out of cartilage, but was a pro- duct de novo, replacing the latter. So thought Albinus,§ and others of his time. It is true, however, that, however obscure may have been the de- rivative nature of this tissue, both Malpighi|| and Leeuwenhoek^f had * Todd and Bowman ; Cyclop. Anat. and Phys., Art. Osseous Tissue, f Valenciennes; Comp. Rendus, Nov. 25, 1844. % Leidy; Amer. Journ. Med. So. January, 1849. I Albinus; Academicarum aduotaliorum. Libriooto. Ley den, 1754. Lib. vii. cap. vi. p. 77. II Malpighi ; Opera posthuma, London, 1797, p. 47. % Leeuwenhoek; Anatomia Ossium, Leyden, 1689, p. 11. ITS PHYSIOLOGY AND PATHOLOSY. 719 perceived to some extent its immediate composition, recognizing what they called "fibres." Most willingly do I omit a consideration of these elder authors. "Well-grounded labours, and those the influence of which extended forward into the modern times, do not date farther back than the time of Purkinje,* whose results were published by Deutch, in 1834. He recognized the corpuscles known under his name, with the canaliculi, and the concentric arrangement of the lamellae. But this significa- tion does not appear to have been clearly made out. He, or rather Deutch, supposed that these radiating lines (canaliculi) were tubes filled with calcareous matter, and therefore served some ulterior pur- pose in ossification. Soon after this, the work of Miescher,"j" already quoted, appeared. He followed closely in the paths already trodden before him, but expresses a different view from that of Purkinje as to the nature of the canaliculi. He did not find them filled with ossific matter ; neither could he trace them through the concentric lamellae. I notice this point here, because it well shows upon what minute points of structure men were at that time engaged. As I have previously remarked, a high estimate is to be placed upon the labours of Miescher, not only from the great care with which they were made, but because he recognized the necessary pre-existence of cartilage for the formation of bone, and supported the view in a manner which would be well worthy of researches of the present time. This foundation being laid, the labours immediately subsequent were upon still more important points — the immediate phenomena of the osseous formation, and the part which each portion played in pro- ducing this result. In the works of Gurlt,J Schwann,§ and Gerber,|| these subjects have received the most careful attention, and as the views therein expressed, although dissimilar, will frequently be alluded to here- after, it may be well to notice them here in a particular manner. Schwann, from the thoroughness of his studies in this direction, should be entitled to a very correct opinion as to the nature of car- tilage, in both its primary and secondary conditions. He was in- • Purkinjej loc. citat. f Miescher; loc. citat. % Gurlt; Lehrbuch du vergleiolienden Physiologie des Haussaengetheire, Berlin, 1837. ^ Schwann; loc. citat. 1839. |{ Gerber ; Handbuch der allgemeinen Anatomie der Menschen und des Haussaen- getheire, Berne, 1840. Or Gulliver's edit. London, 1842. 720 THE cell: clined to adopt, as correct, the opinions of Miesclier, who preceded him, and especially as to the important point of the identity of the Purkinjean corpuscle with the pre-existing cartilage-eell, and not with its nucleus. He therefore regarded the canaliculi " as hollow pro- longations of the cells into the cellular substance." This may appear a small matter; but, as will soon be shown, on it rests the clearest doctrines of osteogenesis, viz. those of immediate substitution. Gerber, on the other hand, and with him, Gulliver, I think, are of the opinion that the Purkinjean corpuscle is the nucleus of the cartilage-cell, and that the canaliculi are nuclear stellations. This view has, I well know, some analogous support in the stellate nuclei of many vegetable cells; as, for instance, those of the common geranium {Pelargonium). The same view was entertained by Todd and Bowman.* Now, if the opinion that the nucleus and the cell are histologically the same, as I have advocated on a previous page, be assented to, it would appear of no importance to cavil about this point; for, whatever capacity would be given to the cell, would be given to the nucleus also, and therefore we could look for stellations of the one as well as of the other. But this point has other bear- ings, as we shall soon perceive. The investigations of Mr. Erasmus Wilson,"}" made in the summer of 1841, seem to have been attended with particular results. He had watched the development of bone, and expressed the opinion that the canaliculi deserved the name of " converging tubuli," from their manifest tendency towards the Haversian canal; and as this tendency appeared constant, it gave him the impression that they served as a necessary means of connection of the periphery with the centre of the concentric lamellae. I am not aware, however, that Wilson entertained any positive opinion of his own on the mooted point of Purkinjean corpuscle and cartilage-cell. On this topic, the view of HenleJ is diiferent from both those of Schwann and Gerber above mentioned. He "regarded the Purkinjean corpuscles as the cavities of cells, of which the thickened sides form the fundamental substance, and the osseous canaliculi are the tubes which penetrate the cavity of the cell in the thickened sides of this last, as are the porous canals of vegetable cells." But I must confess that this description, given in Henle's own * Todd and Bowman ; Physiological Anatomy, p. 108. f Wilson; The Anatomist's Vade Mecum, London, 1842. X Henle ; TraitiS d'Anat. g^nerale, &c. Trad, par Jourdain. Paris, 1843, vol. ii. p. 409. ITS PHYSIOLOGY AND PATHOLOGY. 721 •words, does not appear clear to me, neither do I think the reasons for it, subsequently stated, sufficient for its adoption. Flourens,* in the same year, published his results upon the forma- tion of bone. But they relate chiefly to another department — its production in connection with the periosteum and the so-called me- dullary membrane, the existence of which he supports, regarding it' as a mere extension of the former. These observations were con- tinued, and published in 1845 ;t and in the same year there appeared a long paper by MM. Brull^ and Rugenny.J To this last, however, I need not here allude. The researches of Mr. Tomes§ were quite extensive, and were published soon after. He described, among other things, the ultimate structure of bone lying between the cana- liculi and lacunse, as consisting of minute spherical granules, and not being a homogeneous substance, as usually described. In regard to the other microscopic points, his view is that, after the formation of the ossific tubes (canaliculi) in the process of ossification, the lat- ter are filled up by a deposit of osseous granules, and while this deposition is going on, small cells are left, which are the rudimentary Purkinjean corpuscles. More recently, and within a few years, important researches have been made; and it is singular that, after so many varied opinions should have arisen, some of the earliest views are advocated. Thus, Hassaliy agrees with Schwann, and says: " The Purkinjean corpuscles are to be regarded as complete corpuscles, the canaliculi of which are formed by the extension of the cell-wall, which is proved by watch- ing the formation and development of bone." This same view has since received a very able confirmation from the studies of a most excellent observer. Dr. Leidy ;Tf and these were Jnade upon the ossifying frontal bone of the human embryo of two inches. Here he traced the immediate transition of the cartilage- cell into the Purkinjean corpuscle. In this connection, the name of Dr. Sharpey** should not be over* passed without mention. His studies upon osteogenesis have been quite extensive, and he has revived the old opinion, that true bone is * Flourens; Comp. Eendus, 1841. f Flourens ; Comp. Eendus, Deo. 8, 1845. { BruUe and Rugenny; Annal. des Sc. Nat. Nov. 1845. § Tomes; Cylop. Anat. andPhys. Art. Oss. Tissue, March, 1846. II Hasaall; Microscopical Anatomy of the Human Body, London, 1847-50. T[ Leidy ; Proceed. Phila. Acad. Nat. Sciences, 1848. ■ ** Sharpey; Human Anatomy, by Jones Quain. Ed. byB. Quain andWm. Sharpey, London, 1847 ; Introduction. 722 THE cell: sometimes developed in membranes, and without the pre-existence of cartilage. This point he thinks he has demonstrated by watching the development of the cranial bones; and Dr. Carpenter (as he affirms in his Human Physiology) mentions that his own researches have confirmed them. For a description of these changes I must refer to his work, as they cannot be clearly and laconically stated here. A criticism upon this view will be passed when I state my own results; and, by way of conclusion of this historical view, I will add that, quite recently, two excellent observers, Kolliker* and Robin,t after a somewhat comprehensive practical review of the whole subject of osteogenesis, express their concurrence in the old opinion of an intramembranous form of bone-genesis. This last would certainly be enough to make one hesitate as to an opposite opinion ; but, as I shall now proceed to show, the whole matter can be quite definitely comprehended by proceeding step by step.J The true cartilage tissue, when existing as such, is always invari- ably the same. Two varieties, however, dependent upon a degree of organization, are formed. The first, called cellular-cartilage, or comprising those of a transient nature, and ultimately passing on to the formation of bone, consists of nucleated, well-defined cells, lying in a semi-solid punctiform stroma. The second, called fibro-cartilage, consists of the same kind of cells, lying in a network of fibrous tissue, which last is only a farther developed condition of the punctiform stroma. In this last, this fibrous tissue may so increase that the true cellular element entirely or almost entirely disappears ; and hence the transition of fibro-cartilage into fibrous tissue. Another division of cartilage is into the temporary and permanent; but this is con- ventional only, for they differ in no essential particular from each other. It is evident from the above view that all cartilage is originally the same, viz. cellular, appearing as such in the embryo. Its pri- mitive formation there takes place, according to my own observa- tion, in the following manner: At those points at which cartilage, * Kolliker; Anatomie Mikroskopiache, &o. bd. ii. p. 376. t Bobin; Mem. de la Soo. de Biologie k Paris, 2ienie ann. 1850, p. 119. J I regret being unable to allude in some detail to a oomprebensiTe Memoir on this subject by Tomes and De Morgan, recently presented to the Royal Society. It is not yet published, but there is an abstract of it in the Lond. Med. Times and Gaz. Oct. 2, 1852. From this abstract, I should judge they do not believe in the formation of bone without a pre-existent cartilage. It would also appear that they think that the nucleus of the cartilage-cell becomes the Purkinjeau corpuscle. ITS PHYSIOLOGY AND PATHOLOGY, 723 and afterwards bone, is to appear, there exist cells, which, as to phy- sical characteristics, cannot be distinguished from those which are to form other tissues. A part of these cells are condensed into a punc- tiform stroma, leaving open spaces here and there, in which per- sist the original cells, from one to three or four in each cavity; there is, then, a finely granular stroma, in the midst of which lie free nucleated cells. At first, this separation is marked out by faint lines only ; but, subsequently, it becomes more marked, and, finally, after consolidation, presents the true cellular cartilage. As this stroma is formed closely about the cells, it is not correct to say that cavities are at first formed in the stroma, and in which the cells repose. However, subsequently, the cell-membrane, lying in direct contact with the stroma, blends with it and is lost ; and then there appears a cavity in which the nuclei of the old cell persist. But as these changes take place at an early period, one does not often see anything but the nuclei; and as these are nucleated, and resemble cells, it is proper that they should be designated as such. Fig. 24. 'i§!?i#''^' a. Cartilage and its formation, u. Cartilage just forming, appearing as cells lying in a finely punctated stroma, from Tertebral column of foetal goat of one month, a. Cellular or temporary cartilage, from femur of a foetal goat. c. Kbro-oartilage (permanent), the punctated stroma having hecome fibrillated, giving the whole a nidiform aspect. Erom articular cartUage. (Magnified 822 diameters.) In fihro-cartilage, the same early changes occur, but the stroma is farther developed, and a fibrous or fibrillated tissue is the re- sult ; when this has occurred, the cells (or rather cell-nuclei) lie in nidiform cavities, each of which quite resembles a bird's nest with 724 THE CELL: eggs. It is only the cellular form of cartilage which is developed into bone, and this osteogenesis is, as we shall now perceive, only a kind of displacement of one material for another. We will suppose the cellular cartilage is formed ; then, as the ossific matter is about to be deposited, the vascularity of the cartilage is much increased, so that the substance presents a pinkish hue ; then a kind of liquefaction of the intervening stroma appears to take place, so that the cartilage^' cells seem no longer confined irregularly, but are, for the most part, free to assume almost any relative position. A tendency with them to an arrangement in linear series is then manifest. These rows run parallel with the long diameter of the bone, and are separated from each other by the intercellular matrix, which consists of the partially liquefied stroma. It is thus, when these rows are formed, that the future bone may be said to consist of a fasciculus of tubes in which the cartilage-cells are situated ; and I have often thought that, if a tranverse section could be then made, it would present a very uniform appearance of this kind. This in- tercellular matrix constitutes the primitive ossific rete, in which the calcareous salts are first deposited. This first deposition having taken place, the cartilage corpuscles are situated in cup-like or rather cylinder-like cavities. Fig. 25. Formation of bono in cartilage, from tibia of foetal goat of two months, o. Cartilage-cells arranging themselves in a linear manner, and septa appearing between them, c' The stroma and cells so Sir ossified that all are blended together. S. Transverse section of a, showing the cylindrical tubular arrange- ment, c. Ossification still farther progressed, the aqueous portions being absorbed, the cells are brought nearer together, and appear shrunken and irregular, i. Still farther progress, the canaliculi shooting out from the cells, in some of which there is a trace of the old nucleus; thus showing that the Purkin- jeau corpuscle with canaliculi are the transformed cartilago-cells. S. Appearance of septa fading away. y. Nuclei disappearing, t. Nucleus persistent. (Magnified 200 diameters.) ITS PHYSIOLOGY AND PATHOLOGY. ' 725 Before this has occurred, however, the cartilage-cells, and thg substance immediately surrounding them, are likewise charged with calcareous matter. The cells become smaller, and, in contracting, assume irregular forms; the septa, separating the tubes in which they formerly lay, become more and more indistinct, from the uni- versality of the calcareous deposition. Finally, there is perceived a grayish mass, with but little regularity, and variegated with these irregularly shaped bodies — the future Purkinjean corpuscles. But we will look at the process a little more minutely. By this calcareous deposition, the aqueous parts of the tissue disappear or are absorbed, the size of the whole is reduced, and the cartilage- cells brought nearer together ; the tissue, therefore, is much more compact, but still does not lose all of its original characteristics. The tubes, of which we have spoken, form the concentric larfiellse, the corpuscles having arranged themselves in a regular manner around in it ; and, therefore, a transverse section shows the bone to be made up of solid cylinders, instead of hollow tubes, as before the deposition of the calcareous matter. The cartilage-cells are transformed into the Purhinjean or osseous corpuscles. This I have clearly observed, and have traced all the phases of the change. When they exist in the cup-like cavities, their nucleus is prominent. But as ossification goes on, the nucleus gra- dually crumbles away, and, by the time ossific matter is deposited in the cell-walls, little of it is seen. The cell-walls, however, re- main, but have become shrunken, and, from the absorption of the aqueous portion of the intervening substance, they are brought nearer together ; however, they hold regular concentric relations to the central portion of that which was the tube, and this central portion is to be the Haversian canal. When the cartilage-corpuscles begin to shrink, radiating lines are seen running from each ; these ap- pear to commence with the corpuscle and radiate from it, and in shooting out in every direction, they meet with those of neighbouring corpuscles, and thus are joined together on every side. Thus far all seems clear. The cartilage-cells lie in the midst of an amor- phous stroma; this last partially liquefies; the cells then arrange themselves in rows ; these rows are separated from each other by this intercellular stroma, and form more or less regular tubes; in the walls of these tubes the ossific matter is first deposited, and afterwards in their contents, both cellular and granular. These tubes form, each, a system of concentric lamellae — from the arrangement of their con- tents in a concentric manner — and this occurring around a central 726 THE cell: cavity, forms the Haversian canal. The Purkinjean or osseous cor- puscles are the pre-existing cartilage corpuscles changed by the ossific processes. The next question is, what are the canaliculi ? Are they prolonga- tions of the cartilage cell-membrane, as Schwann has supposed ? As far as my own observation yet goes, I must say that I have seen no evidence that such is true, excepting their general appearance. On the other hand, there are facts which oppose such a view. In the first place, the canaliculi do not commence to form until the calca- reous matter begins to be deposited, and, as the cell-membrane is then ei^'hex filled with calcareous matter or absorbed, it could not well send out prolongations. Moreover, these prolongations are often of such a length, and branch and rebranch so often upon themselves, that it can scarcely for a moment be entertained that they are thus formed. I ask, is it not more probable that they are channels for the escape of aeriform matters from the interior of the cell ? For the cell, ex- isting in the midst of an ossifying mass, would retain its animal matter longer than the rest of this tissue ; and this animal matter would give rise to gases seeking their escape in every direction by percolating the surrounding semi-solid mass ; and in behalf of this view, perhaps Wilson has rightly named them " converging tubuli," formed as they are by currents naturally seeking or converging towards the nearest outlet. I do not, however, express this as a well-grounded opinion, but simply as a probable hypothesis. We shall soon see what other rea- sons there may be for its adoption. Fig. 26. Microscopical view of TranBTcrBc Section of Bone, from rcmur (liuman). o. The concentric lamellffi, wifli Haversian canal and Purkinjean corpuscles. (Magnified 175 diameters.) b. Purkinjean corpuscles iso- lated, to show irregular form and the canaliculi. (Magnified 460 diameters.) ITS PHYSIOLOGY AND PATHOLOGY. 727 In these phases of formation, some of the nuclei of the cartilage cells, or even other adventitious cells of a small size, may not be dissolved, but become ossified as such, as are the cells in some of the lower fishes. You would then find them as cell-like granules, scat- tered irregularly through the osseous tissue. These are not the granules spoken of by Mr. Tomes, but distinct cells of a larger size, varying from 1-3000 to 1-2000 of an inch in diameter. It is in this way that I account for the occasional presence in the spongy tissue of the long bones of small spherical bodies, first discovered by Dr. Holmes, of Boston, who met with them early in 1849. Subsequently, however, Lebert* has fully noticed them. As their presence 4s i\ot constant, and does not apparently involve any pathological condition, the above view of their nature appears to be correct, f Such appears to be the mode of proceeding of the formation of the compact tissue of the bones of the higher vertebrata, as I have studied it in foetal goats. The process is simply one of substitution, with that contraction and modification of form which must necessarily fol- low when a soft is replaced by a sclerotic tissue. This law of substi- tution is everywhere the same ; but, to be sure, there is a difi"erence in some of the steps of its progress in the different kinds of bones. Fig. 27. «-'■ # The peculiar long corpuBcles Bometimes met with, from medullary tissue of head of femur. The cor^ puscles, for the most part, haye nuclei, some of them seyeral. (Magnified 350 diameters.) The spongy character of the internal or middle portion of bones appears to be produced by the absorption, by the numerous vessels there situated, of the lighter portion of the primitive cartilaginous * Letert ; Compt. Kend. dee Stances de la Soc. de Biologie ^ Paris, Oct. 1849, p. 149. f I think the " ossified cells," as they are called by Tomes and De Morgan, must be the same bodies. See their "Memoir on the Structure and Development of Bone," read before the Eoyal Society, but of which I have seen an abstract only in the Med. Times and Gaz. London, Oct. 2, 1852. 728 THE cell: base, and a consolidation towards the periphery. This, however, is a point having a teleological bearing, for by such an operation, the bones possess the greatest strength and lightness combined, attainable with the same amount of material. These phenomena of genesis just described belong especially to the higher vertebrates. In the lower classes, they are far from being of this complicated character. Such is the case with many fishes. The concentric lamellae do not exist, and therefore there does not occur any linear arrangement of the cartilage-cells; but they become ossified in situ, their canaliculi radiating from every side, giving the whole a most , regular and beautiful appearance. Everything is left exactly as when a soft tissue, cells, nuclei, and all, giving you the impression that it had suddenly been charged with calcareous matter. Such appearances may be seen in some of the bones of the sword-fish. The cartilage of cartilaginous fishes may be said to differ from the common cartilage of the higher vertebrates. In fact, it cannot be properly called true cartilage, but is, if I may so express myself, osseous tissue in a cartilaginous dress. This will be clear if I make one or two explanatory remarks. As has already been stated, Va- lenciennes* has shown that the cartilages of cartilaginous fishes and the Cephalopods contain gelatine, and not chondrin. Now, Miillerf has shown that all ossifying bone contains chondrin and not gelatine, and after the process of ossification has taken place no chondrin is found, but all is gelatine. Therefore, bones are, so to speak, gelatinous, and not chondrinous. The same we have just seen is true of the so-called cartilages of the cartilaginous fishes. This will make clear the state- ment just made. I much regret that no examinations (at least of which I am aware) have been made of the chemical character of the embryonic condition of cartilage in these lowest fishes, for I should venture to predict, upon the above premises, that they would be found chondrinous and not gelatinous. The tissue forming the cartilaginous skeleton of these fishes, as I have had an opportunity to examine it, is composed of oval or spherical cells, resembling the common cartilage-cells at an early period of development. These have become hardened in situ, but not calcarified, and never have I met with any having the canaliculi * Valonoiennes ; loc. ciiat. Comp. Rend. Nov. 25, 1844. t MuUer; Poggendorf Annalen, Bd. xxxviii. p. 316; orUeberden feineren Bau der Geschwiilste, Berlin, 1838, Erster Band, pt. ii. ITS PHYSIOLOGY AND PATHOLOGY. 729 radiating from them. From all these data, I think we may justly conclude that, in these lower fishes, we meet with bone-cartilage and not ^jrith true bone. The cartilaginous and osseous tissues, as we hare thus just described them, may well be said to belong to the vertebrata only. Among the invertebrata, the only class having any claim to our considera- tion in this respect is that of cephalapoda. With these I have no experience ; but Siebold* says that their skeleton has a structure like that of the true cartilages of the vertebrata. But this similarity is probably an analogous instead of an homologous one; exactly as may be said of some of their other tissues ; for our most compre- hensive knowledge of these two kingdoms leads us to infer that all true homology ceases with the boundary of each.f In regard to the mooted point, whether true bone is ever formed without the pre-existence of cartilage, it follows from the above that, as true bone contains osseous corpuscles — and these are modified cartilage-cells — the answer would be in the negative. VIII. Crtstalline-Lens Tissue. This is the last tissue to come under our consideration, and I should have omitted it here altogether, had I not watched the pheno- mena of its genesis. This genesis takes place from cells, originat- ing, almost without a doubt, according to mj own mode of cell gene- sis already described. As would be inferred from its very function, there is perhaps no tissue in the economy having so delicate a structure. It is no won- der that the attention of the early anatomists should have been excited to tlie consideration of the fact that an organized structure should be able to act exactly like an unorganized vitreous substance. Its very function precluded any correct knowledge of its structure with the ordinary aids of vision, for it is nearly transparent. How- ever, from studies upon the inferior animals, its tissue had long been recognized to be "fibrous." But how these fibres were art-anged so as not to interfere with the transmission of light was the mystery. This point Sir David Brewster J first elucidated by means of polarized * Siebold; Comparative Anatomy by Siebold and Stannius, trans, from German, &o. &c., by Burnett, vol. 1. g 231. t Since the above was written, I have had an opportunity to study the cartilage of the Cephalopods as illustrated in the common Sliuid {Loligo illicehrosa), and my ob- servations agree with those of Siebold above referred to. J Brewster ; Philosoph. Transact. 1833. VOL. VI, — 47 7B0 THE CELL: light, and showed that they were united by dentated edges -which lock into each other. Since the days of cell studies, this tissue has been shown to, take its origin in cells like that of others. This was first pointed out by Valentin* from studies upon embryo sheep. Since then the same has been observed by Werneckf and Schwann ;J the last of whom has applied his cell-theory to the phenomena observed. These last three observers agree as to the nature of the meta- morphosis producing the fibres, viz. that the fibres are simply elon- gated cells, which cells, Schwann has concluded, arise always from a pre-existing nucleus, because many of them were found nucleated. However, Schwann freely admits that his observations on this sub- ject have not been complete. More lately still, the subject has been examined by Martin Barry§ and Mr. Toynbee,|| both of whom take an opposite, or rather dif- ferent view from that of Schwann, viz. that the fibres are formed by Fig. 28. 2. b. ,''•■■' 1 "■•• I '.' '. :,'.'!'.' ^ ■>;': \ n:? ■4 ;5 >^ ; 1- % .V' l'.'-' ,'! ■ 1 i 1 1 1 1 ■i' • ■V ■'■■■■• :■ 11 1 ■k- i H^ \i a. CrystaUine-lens fibres from a cat. b. Crystalline-lens fibres from an owl [Strix virginiantu). All represented slfghtly granular for effect. the coalescing of several cells into one, forming at first a tube after the manner of that of muscular fibre. Tf * Valentin ; loc. Hi. Entwickelungsgeechichte, p. 203. t Wemeck ; Anemon. Zeitsohrift, bd. t. p. 414. f Schwann ; loc. cit. p. 100. I Barry ; Embryological Eeaearches, third series. II Toynbee ; Memoir on the Non-Vascular Tissues. PhUos. Trans. 1841. If In anatomical and histological works, the fibres of the crystalline lens are de- scribed as having dentated edges, which fit into the corresponding structure of the ITS PHYSIOLOGY AND PATHOLOGY. 731 The following is what I have observed both as to the genesis of the cells and their transformation : — In the foetal goat of two months old, and six inches in length, the crystalline lens is biconvex, and made up of three parabolse, the apices of which meet in the centre, thereby leaving at that point a spheri- cal triangular space. The central portion of the lens, extending to near the periphery, is opaque, and this opacity is greatest in the centre, becoming less and less so as you approach the outer edge. The part most opaque is composed of minute granules or utricles, which, as you approach the outer edge, are larger and larger, until on the very border of the opacity they are seen as quite sizable vesi- cles, some of which are nucleated, in fact, cells. Thus you have, in this opaque central portion, an appearance of all the transitionary stages of minute utricles to large vesicles and cells ; and this develop- ment has occurred by mere expansion of the former, and not by the Schwann mode of cell development. At the confluence of the opaque portion with the clear peripheric border, there is perceived a tendency of the cells or vesicles to ar- range themselves into rows or serial longitudinal groups, which rows are parallel with the long diameter of the parabola. Then, by the confluence of these rows of cells, tubes are formed, and from these the fibres. Therefore these tubes have their origin, not by the elong- ation of single cells, as Schwann has supposed, but by the coalesc- ence of piles of cells into one continuous tube. These observations, therefore, correspond with those of Barry and Toynbee, as above mentioned. In this instance it was truly beautiful to observe, how the clearing up of the structure took place just in proportion as the constituents assumed the cell-form; thus showing that this tissue only attains its wonderful function by the remarkable process of cell-genesis — a process by which form and order appear to start out of chaos, and that which is dark and obscure is made almost as clear and transparent as light itself. And when one has seen these contiguous fibres. This serration was, as is well known, first pointed out by Brewster with the lenses of fishes. But from a rather detailed examination of the subject of late, I am satisfied, that, whatever may be said of it with fishes, it does not belong to the higher animals. With perfectly fresh specimens from man and many of the higher mammalia and birds, I have been unable to perceive the least dentation. The fibres are perfectly smooth and contiguous ; this has been the Invariable appearance when very fresh specimens were used. I cannot bfit believe, therefore, that this creuulated condition is due to a change in the fibre after death ; a change, perhaps, like that lead- ing to like appearances in the blood-corpuscle, and due to a partial abstraction of its liquid contents, the sheath of the fibre becoming ruffled. 732 THE CELL: things, does it not bring home to the mind with suggeStiye grandeur and beauty, the recollection of that fiat of the Deity, which is re- corded — "And God said let there be light, and there was light?" We will now see how these phenomena are manifested in oviparom vertebrata. In the chick which I have especially examined, the phases of formation are best examined at about the eighth day. Here, as in the former instance, a part is cellular and granular, and another part tubular, or soon to become so. Fig. 29. ■'■'./'r'AP B „ O ^ ° o„ ° 0, •& Formation of crystalline lens in mammalian vertebrates, from foetal goat of 2 months, a. The leua ■with a dark centre, clearing towards periphery, where there is a light transparent border. &. Minutely granular structure of centre, composed of Tery minute utricles, which become visibly vesicles as you approach the out«r edge. c. Vesicular or cell-structure of portion where pellucid border passes intotrang- parent periphery. Some are distinctly nucleated. Size 1-2000. d. Structure of transparent periphery composed of tubes formed by linear aggregations of the cells. — a, &, and c, magnified 225 diameters. tZ, magnified 450 diameters. The minute vesicles are here observed, gradually expanding, until they have reached a certain size, when they become nucleated. There are, therefore, both nucleated and non-nucleated cells. When the cells have become nucleated, they begin to arrange themselves into rows, and then by coalescence form tubes. There is, however, this difference between those of the goat and chick, as I have observed : In the goat, several rows of cells form a tube, while in the chick the same result is obtained by a single row. Afterwards, the nuclei gradually disappear, and beautiful transparent fibres appear. Fig. 30. O Q" O 6% „9, S o c = ;? ° o o o o O o Formation of crystalline Ions in oviparous vertebrates, from chick of 8 days. a. The lens with a dark granular centre, and transparent border, b. Granular or minutely utricular structure of the central portion, c. Vesicular structure of portion intermediate between the centre and clear border, d. Vesi- cles that have become nucleated, e. The same arranged in rows. /. The same coalesced or fused partly. g. A single row of cells, forming a tube, not so much by a coalescence of their own waUa, as by a plna- matic membrane enveloping them. (Magniaed 360 diameters.) ITS PHYSIOLOGY AND PATHOLOGY. 733 The crystalline-lens, therefore, is truly a tissue of cell-metamor- phosis, and from its delicacy and beauty has well thus briefly arrested our attention. It -will be seen 'that the phenomena of this metamorphosis, as I have observed them, are of the same nature as those involved in the formation of muscular fibre, that is, by a kind of intersusception, and^wof, as Schwann has thought, by immediate fibre-transition. With this, I close the genesis of cells in particular, and their meta- morphoses into special tissues. CHAPTER IV. CELL-FUNCTION, OR THE PRODUCTS IN CELLS. In the preceding chapter we were engaged in tracing out the genesis of cells in particular, and the phases of their metamorphoses into special tissues. However carefully this was or may have been done, it gave us no insight into the conditions of cells as individual, active agents. As yet we have become acquainted with them only as physi- cal objects, and we know them as we know a machine, by its size, shape, and general aspect. Such is the broad distinction between anatomy and physiology : the former teaches us nothing of the latter, and the vice versa is nearly equally true. Our knowledge of what, cells do (not become) must be learned of itself, and proved by expe- rience. I propose, therefore, to consider them in this light, taking up each class by itself, as was done in the genesis. I should mention, however, that cell-function, or the products in cells, can belong only to individual cell-structures, or those in which the identity of the organ as such is not lost in a compound tissue. I. Epithblial-Cbll Function, The epithelial cell is the great secreting agent of the animal econo- my. By it, the essential products of life and its reproduction are eliminated ; and on it, rest all the grand phenomena of nutrition and secretion. Its full discussion, therefore, would involve many points for consideration, which otherwise would not fall within the domain of this work. I have already pointed out its anatomical peculiarities, which, however diversely it may be situated, are invariably the same. 734 THE cell: It is the essential structure in all glandular organs, constituting the skin, and covering all mucous and serous membranes. These are facts so -well recognized in science, that their consideration in detail is not necessary. It would be easy for me to take any gland, and, by reference to my sketch-book, demonstrate its leading features. The mammary gland, for instance, could be taken, and by reference to observations throughout the mammalian vertebrates, its intimate structure be shown to consist of ampuUse, lined with epithelial cells, by which alone the milk is formed or elaborated from the effused plasma of the blood. Or, in the same manner, I might take the liver, which appears to have an existence in the animal economy, even more common than that of the heart itself,* and show that the elimination of bile is per- formed by cells alone among the lower invertebrata y\ they exist as simple cells, having no basement stroma and no ducts ; in fact, in the simplest form. As we advance, we find these cells having more complicated relations with nutrition and secretion, and wrapped into an organ of a separate and distinct character. Without entering into any of these discussions as to the minute anatomical relations of these cells, and which has been a very mooted point of late, I think I may say that the fact of the cell-origin of the bile or its analogue is quite clearly established. The remarks just made belong in common to all the other glands of the body which elaborate liquid products, wherever they may be situated. It is not for me to take up here their anatomical relations. I have finished with them when I make the general statement as a scientific fact, based upon my own, as well as upon the observations of others, that the peculiar products of each gland are eliminated by them as nucleated cells. If it is asked how such is accomplished, I should reply, by the acti-on of the cell- wall ; it being the peculiar pro- perty of the walls of liver-cells, for instance, that they should elabo- rate bile from the plasma of the blood, which transudes through them and is changed to bile by coming in contact with the nucleus. The same is true of other secreting cells. Beyond this, physiology and experience have taught us nothing ; and what is more, it is now diffi- cult to conceive how they ever can. The why that one cell should * The remark of Haller is not broad enough. He says: "Lat6 per animale regnum hepar dominatur, et si paulo angustioribus finibus oontinentur, quam aut intestinum— aut con." t Siebold ; Comparative Anatomy, by Siebold and Stannius, transl. by Burnett, vol. i. g 37. (This I have seen myself also.) ITS PHYSIOLOGY AND PATHOLOGY. 735 secrete bile, and that another, exactly like it in physical aspect, should secrete milk or saliva, Vill long remain an enigma in phy- siological science. The solid products in epithelial cells now deserve our attention, and they possess full the interest of those we have just been consider- ing, because they have an individuality of their own. I refer here to the embryo as the product of the ovum, and to the spermatic particle as the product of the sperm-cell. What the function of these two cells is, and how it is discharged, and what is the nature of the product, is worthy of our consideration in a more than usual degree. Some detail will, therefore, be necessary. We will first refer to the homological conditions under which the ovum and sperm-cell are to be regarded. The ovum is the sole pro- duct of the ovary, and the sperm-cell that of the testicle. In a histological point of view they are the same, and although it might be difficult to make this plain with the higher animals, the conclusion is forced upon us when we study some of the invertebrata. With many of these last, there are no outward distinctions of sex, and those which are internal are purely microscopic. With many of the Radiata, upon which I have of late been considerably at work, this is especially true. The testicles are situated exactly as are the ovaries, and the testicular ampullae correspond in number, size, and general aspect with the ova, and one can be distinguished from the other only by its contents. This is so, for instance, with the asteroid Echinoderms. In the Bryozoa, which are androgynous, I have found these dis- tinctions even less marked. Thus in the genus Alcyonella, there are a few cells in one part of the animal, which go on to form ova, while other cells, apparently identical in physical points, go on to form spermatic particles. Among the Annelida, the same is seen in a truly beautiful manner. Take, for instance, the genus Nais. Here you find the ova, situated in a row on each side of the alimentary canal, each consisting of a little grain about the size of a pin's head. In the male there are similar bodies, having exactly the same locality ; these are sperm-cell cap- sules; and the only difi"erence I have found between these little grains is, that they are white in the male, and yellow in the female. Among the higher invertebrates, as, for instance, with the Articu- lata, these homologies of the two organs are distinct, but less so than in the instances I have just quoted. From all this it may be safely inferred, that the ovary and testicle, as individual organs, consist only 736 THE CELL: of a tissue whicli supports a cell-structure, which is the essential part. Now as this cell is an epithelial cell, we can truly say that, histolo- gically, they are one organ. But perhaps the best part of the argu- ment is yet to come, for by illustrating the processes they undergo, the morphological identity will be clearly made out, although we should not forget that there is a broad teleologieal difference. The ovum exists at first as a simple nucleated cell, and it goes on to the attainment of its full size by the endogenous formation of cells within it. This last takes place out of the fertile blastema, which transudes its walls, and according to the laws of cell-genesis already pointed out. Having attained its full size, this endogenous increase ceases, and then the ovum is ready for fecundation. By this last pro- cess, it is endowed with an individual potency, upon which succeed ' changes ending in the elimination of a distinct being. These phe- nomena have their first expression in the segmentation of the viteUus, dividing equally into two, then into four, eight parts, and so on,- un- til the result of the last division is quite small, the whole being reduced to a granular mass, out of which the embryo is shapened and formed. Fig. 31. Ova and the vitelline segmentation, a. An ovum in natural state, h. Segmentation singly and dou- bly occurred, c. Segmentation completed, and ovum ready for the morphological changes of the cm" bryo. (Reduced size.) But if this segmentation, for this definite object, is always indica- tive of an impregnated state, the simple phenomenon of segmenta- tion has not this signification, for it occurs in many ova, to a limited extent, before fecundation has taken place. This I have observed with the ova of fishes and many of the Articulata. You may ask : What, then, is the signification of vitelline segment- ation ? To this it may be replied, that it is the first and only un- mistakable expression of vitality we know a cell or an ovum to pos- sess. In common cells, and in the unfecundated ovum, it is an abortion ; ITS PHYSIOLOGY AND PATHOLOGY. 737 but from the act of fecundation it receives an individual power, so that it goes on, ending in the preparation of the material from which Fig. 32. ^' Ji - 0^% ^^^^ Ova of common Cod {Gadus morrkm), showing limited fiasuration of Titellus, a. Ora resembling nu- cleated cells. 6. The same, with fissuration to number four. the new being is evolved. Here it has acquired a positive character ; and perhaps the best evidence that segmentation to a definite end lies at the bottom of the primitive development of all new individual beings when produced by means of eggs, is the fact that it occurs most extensively in those portions of the embryo that afford the highest expressions of the animal as such, viz. the nervous system. The changes supervening upon this vitalizing process of segmenta- tion, and which are the working out of the future embryo and the allocation of its organs, constitute the science of embryology. They involve details as numerous as the types of the whole animal kingdom, and cannot, therefore, be taken up here. What I have here said of the animal ovum, belongs equally well to that of the vegetable. For this I cannot rely upon my own investigations, but trust to the excellent researches of Robin.* We will now refer to the sperm-cell, the analogue of the ovum. First, it is seen as a simple, nucleated, epitheloid cell. It increases, and after having attained its adult size, it experiences processes which mark its vitalizing character. This consists, as in the ovum, of a segmentation of the nucleus or vitellus, first into two, then into four, eight, &c. parts, the parent vesicle expanding in the meanwhile. So that, after a time, we find the parent vesicle filled with many * See an article by Robin, in Compt. Eendns, 1849, titled " Ovum, the existence of an, as well in the male as in the female of Plants and Animals ; producing in th© one case spermatozoa, and in the other the primitive cells of the embryo." 738 ' THE cell: nucleated cells. These, of course, are of a uniform size, and usually of an even number of the multiples of two.* The next changes are those concerned in the immediate formation of the spermatic particle, which always occurs according to one of two modes, the character and peculiarities of which will be made clear as we proceed. The parent vesicle is filled with nucleated cells, produced by segmentation of the nucleus or vitellus. This is the point from which we will now start. According to one method, and which I have called the special-cell mode, the process of division here ceases, and in each of these cells is produced a spermatic par- ticle. But according to the other method, and which I have called the fasciculus mode, a kind of liquefaction or farther subdivision of these cells ensues, until the whole substance is reduced to a fine granular mass. Then out of this mass, by longitudinal fissuration, the spermatic particles are produced ; as, if I may use this homely comparison, a stick of timber is split, with the grain, into sticks ; the whole forms a fasciculus, and hence the name of this mode. After this general statement we will look at the subject a little more care- fully. It will be seen that the preliminary changes of the genesis of the spermatic particle are identical with those of the ovum. This great fundamental fact at once establishes a unity throughout nature in the process of reproduction. To settle this fact, my own observa- tions have extended over the entire range of the animal kingdom, embracing most of the grand types of structure. Beside, I am now extending it to species, as rapidly as time and opportunities will per- mit. The fact, however, I now consider as well authenticated as any in histology. Our next inquiry is, how is the spermatic particle formed ? Ac- cording to the special-cell mode it is a metamorphosed nucleus. Of this I have satisfied myself beyond a reasonable doubt. It can be well observed among the mammalian vertebrates, or in the Arachnida. According to the fasciculus mode, the particles are formed, probably, from an arrangement in a linear series of the granules produced by the extended subdivision. These unite, and, blending, form continu- ous threads. But this is a point of which I am far from being equally well satisfied. The phases of this change can be best observed in • Sometimes this segmentation is not regular, and then the number of the daughter cells does not correspond to the multiples of two ; thus, there may be seven instead of eight, one of the cells not segmenting. This is sometimes observed likewise ■with the ovum. ITS PHYSIOLOGY AND PATHOLOGY. 739 the insessorial birds. It may be asked if, in this case, it is not the nucleus of the pre-existing cells which is metamorphosed? To this ®l ^'f^i^^l^&fii^^i^^^'i:!^^^^ /^^^^ff^i Formula of the two modes of sperm-genesis, a. Epithelial cells of the testicle micleolateil, which are to he sperm-cells, b. The same with the nucleus undergoing fissuration. c. The fissuration still progressing, d. The parent-Teslcle filled with cells, the result of subdivision. At this point the fissura- tion ceases, when the spermatic particles are produced according to the specidj^cdl mode. e. Formation of spermatic particles according to the speciaJrceU mode ; each divided cell producing one particle. f. One of the cells stall higher magnified, showing how a spermatic particle replaces the nucleus, g, Form- ation of spermatic particles according to the fascicuhcs mode; the granular mass heing the result of the liquej&ction of the cells of d. h. The formation taken place, the spermatic particles lying in a bundle. i. Spermatic particles isolated, showing plicated aspect of head. I should be inclined to answer negatively ; and the evidence against any such supposition is, 1st, you perceive the whole granular mass to be divided in this way ; and 2d, the fascicular manner in which the spermatic particles are found in the parent-cell could not, seemingly, in very many instances, have been attained, only by such a mode of formation. It is, however, a remarkable fact which I have observed, that the number of spermatic particles thus produced, corresponds with the number of cells existing before the granular liquefaction takes place. Thus seeming to show that the individuality of the cell is not lost by this last change, but appears again with a certainty in the result produced. Thus, for instance, a parent sperm-cell con- tains sixteen vitelline cells ; these liquefy and become a granular mass, but out of this last are produced sixteen spermatic particles. There is not, therefore, a real unity in their genesis after the pre- liminary changes have occurred, if we are to judge from appearances alone; but if we consider the identity of the nature of the cell and its nucleus, as formerly established, this unity is established.* * Since the above was written, some special investigations I have made on the sper- matic particles of insects, would lead me to think the point still an open one, if all ITS PHYSIOLOGY AND PATHOLOGY. 741 Figures of spermatic particles of a representative of eacli family throughout the animal kingdom, show- ing the vajriety of forms met with, heginning with the lowest and ending with man. 1. Astrangffl Danas. 2. Alcyonclla (nov. sp.). 3. TuhuUaria laryngsB. 4. Actinia marginata. 6. Asterias spinosa. 6. Echino- ddaris punctulata. 7. Mellita quinquepora. 8. Taenia (noT. sp.). 9. Lumhricus terrestris. 10. Ascidia amphora. 11. Botryllns stellatus. 12. Polyclinum (nov. sp.). 13. Ostrea ednlis. 14. MytUus edulis. 15. Anodon fluviatilis. 16. Unio complanatus. 17. Bolis Bostoniensis. 18. Buccinium ohsoleta. 19. Limax agrestis. 20. Filumnus Harrisii. 21. Pagurus longicarpus. 22. Epeira vulgaris. 23. HEemar topinus suis. 24. Melolontha subspinosa. 25. Antiope Vanessa. 26. JjihcUula grandis. 27. Platesea flesus. 28. Leuciscus chrysoleucas. 29. Salamandra symmetrica. 30. Tropidolepis undulatus. 31. Eana pipiens. 32. Heterodon niger. 33. Emys picta. 34. GaJlus domesticus. 35. Muscicapa tyrannus. 36. Fringilla melodia. 37. Didelphis virginiana. 38. Neotoma fioridana (lateral view). 39. Sciurus hudsoni- cus. 40. Gapra capricornis. 41. Ganis familiaris. 42. Man ('lateral view). From 1 to 7, and from 10 to 16, inclusive, magnified 1500 diameters; the remaining, 350 diameters. The SPECIAL-CELL MODE of the genesis of spermatic particles occurs in the Mammalian Vertebrates; all the Q-rallatorial Birds, also the Accipetres and Scansores ; in the Chelonian, Anourous Ba- traohian, Saurian and Ophidian Reptiles ; in the true Osseous Fishes ; in the Arachnida ; the families Lihelullidse, Phryganeidse, Phasma- dse, and Andrenidse of the Insecta; in all the Crustacea; in the Q-asterofod Mollusca, and in all the Radiata. The FASCICULUS MODE occurs in the Insessorial Birds ; the Cau- date Batrachians ; the Plagiostome Fishes ; the remaining families of the Insecta; the remaining Mollusca ; the Annelida. The spermatic particles eliminated according to the special-cell mode generally consist of a staff, to which is attached a delicate tail. On the other hand, those produced according to the other mode have a filiform aspect, there being generally no distinct division be- tween the staff and a tail. The variety of forms, of which each animal has one, and one only, is quite extended, and presents to us a field of study having not only the deepest interest, but the highest zoological importance, and espe- cially as relating to classification ; for as the spermatic particle is the simplest representative we have of the potential whole of the animal, so may we well regard its forms as constituting the basis of a classi- spennatio particles are not developed by the epecial-cell mode, being therefore meta- morphosed cell-nuclei, and subsequently grouped in a regular fasciculate form. Thus, the very long filiform spermatic particles of some of the Lepidoptera, I have seen developed in special cells, while in other cases these particles may be observed in such a perfect fascicular form as to indicate that they were developed in bundles ; however these bundles are never observed within parent cells, as is true of those of the sparrows. In these last (sparrows), both the size and the length of the particle would seemingly preclude the view of their special-cell development ; for, in some instances, the number of particles thus grouped in a parent cell was such that had they had their development In cells specially, these cells must have been so large that a corresponding number could not have been contained in that parent cell. But the subject needs a careful revision as to this point. 742 THE cell: fication founded upon the simplest and most natural data. But both a description of these forms, and a detail of these classific relations, is a subject of itself alone.* There can now be no reasonable doubt that the function of the spermatic particle is that solely of fecundation, and that this last is produced by it alone. In the first place, the morphological identity of the two particles, the ovum and sperm-cell, as I hare already pointed out, would of itself lead us to infer that the special product of the latter was for individualizing the whole of the former. In fact, such an inference would be in perfect accordance with our highest ideas of the unity pervading natural phenomena. But, aside from this induc- tion, the point has been settled by direct observation. The experiments of Spallanzanif proved this point as clearly as it well could be at that period. Since then the observations of Kolli- ker,J Newport,§ and Agassiz,|| have conclusively settled the matter. The evidence consisted in having the ovum so situated that nothing of the semen but the spermatic particle itself should come in contact with it. I will add to the above the evidence of my own observa- tions, which serve not only to elucidate the above-mentioned point, but also to show that one, or at least a few particles are sufficient for a single ovum. In some of the low Acaridse, as, for instance, those of the genera Sarcoptes and DermaleicJius, the generative organs of both sexes are situated on the inner surface of the abdominal sac. In the female these consist of ova, and in the male they are sperm- vesicles. Now the number of ova and sperm-cells correspond quite closely ; so that while in some species you find ten or twelve ova, there appear to be only about the same number of spermatic particles. There is no semen proper, for the sperm-cells discharge their con- tents as spermatic particles, and the only liquid is that which belongs to the cells. The long period of copulation of these animals is secured by the strong anal hooks of the male fastening into the abdomen of the female. Here, then, just the experiment you desire, is performed by na- * For a farther discussion of this point, see a paper of mine, Relations of Embryo- logy and Spermatology to Animal Classification. Proceedings of the Amer^ Assoc, for the Advancement of Science. Albany meeting, 1851, p. 812. f Spallanzani ; Nouvelles Recherches sur les dicouT. microsoop. London, 1769. I KoUiker; Die Bildung der Samenf aden in Blaschen, Nuremberg, 1846. % Newport; PhUoaoph. Transact. 1851, p. 169; and Proceed. Roy. Soc. June 17, 1852. Agassiz ; Oral communication. ITS PHYSIOLOGY AND PATHOLOGY. 743 ture ; and a better proof of the suflSciency of a few particles could not be obtained. From similar experiments, it has been shown that, in the act of fecundation, the simple contact is enough ; in other words, the sper- matic particle loses none of its material form by discharging its function of vitalization.* If it is asked, how this function is performed, to this it must be replied, that this has not yet been reached by physiological inquiry. And what is still more worthy of remark, it is difficult, in the present state of our relations to science, to conceive how we shall ever be much better able to seize hold of the intimate nature of these phenomena. We may call it by this name or by that, and such words may be adopted, although they serve to cover up our ignorance ; for they are, in some way, and to some extent, expressive of conditions which the scientific mind by analogy alone can comprehend. But, at the same time, it should be remembered that the ultimata of all science having anything to do with vitality, must ever rest on words or conditions equally as vague and unsatis- factory. However, some special considerations on this point will be offered in the philosophical portion of this work.f * See farther, a discussion of this intricate subject in Silliman's Joum. Nov. 1853. f The bibliographical relations of the subject of spermatic particles here deserves notice. The older anatomists, Leeuwenhoek,* Ledermuller,'|"Spallanzani,JGleichen,§ and others, not only recognized their existence, but even studied their form and pecu- liarities. This is especially true of Spallanzani. At the beginning of the present cen- tury, they excited considerable attention, and were especially studied by Prevost and Dumas, || and others ; and the same is true of the time of the improvement in microscopes, about the year 1830. Dujardin,ir Czermak,** Treviranus,tt Von Siebold,JJ and Wag- ner,^J each contributed considerable towards the advancement of these studies. But, on the other hand, they tended to retard its true progress, by asserting that these par- ticles are animals, a view which was supported by Valentin, || || Gerberj^TJ Schwann,*** Pouchet,ttt and others. To.WagnerJ J{ and KollikerJ^^ we are indebted for a complete * Leeuwenhoek ; Anatomia, seu interiora semen, Lugd. 1687. t Ledermuller ; Phyaikalische Beobachtungen du Samen thierchen. Nuremberg, 1756. X Spallanzani ; Nouvelles Kechercbes eur les d6cour. Microscop. London, 1769. § Gleicheu ; Abhandlung ueber du Samen, und Infusions thierchen. Nuremberg, 1788. Q Prevost et Bumas ; Annal. des So. Nat. tom. i. and ii. If Dujardin ; Annal. des So. Nat. tom. vii. pp. 291-297. ** Czermak ; Beitrage zur Lehre von den Spermatozoon. Vienna, 1833. ft Treviranus ; Tiedemann's Zeitachrift, vol. ii. tt Von Sieboldj Miiller's Archiv. 1836, 8. 232, and 1837, s. 381. gg Wagner ; S^agmente zur Physiologie du Zeugung, 1837. gi Valentin ; Eepertorium, 1837, p. 134. W Gerber ; Allgemeine Anat. &c. p. 210. •** Schwann; Mikroscop. Untersuch. Ac. Berlin, 1839. tff Pouchet ; ThSorie positive de Fovulation spontanSe, &c. Paris, 1847, p. 321. ftt Wagner ; Hist, de la generation, &c. Bruxelles, 1841, p. 26. 2^ Kailiker; toe. eit. Berlin, 1841. 744 THE cell: The great fundamental fact at whicli we have arrived by these studies, is the morphological identity of the ovum and sperm-cell ; and, by way of conclusion, I subjoin, in a tabular form, their expression, in a brief manner : — The Sperm-Oell. The Ovum. 1. Is a nucleolated cell. 1. la a nucleolated cell. 2. The Buoleus, increasing and becoming 2. The nucleus (vitellus), increasing and granular, undergoes segmentation. becoming granular, undergoes segment- ation. 3. The result of this segmentation is, that 3. The result of this segmentation is, that each of the subdiTided cells forms a sper- all the subdivided cells, by a metamor- matic particle. phosis, form an embryo. 4. The function, then, of the sperm-cell, is 4. The function, then, of the ovum, is to to eliminate the vitalizing spermatic par- eliminate the vitalized product, the em- ticles. bryo. 5. In the lovrest sense of the term, the 5. In the lowest sense of the term, the em- spermatic particle is alive ; that is, it is bryo is alive ; that is, it is an organized an organized acting form. But it is so acting form. But it is so in the lowest only in the lowest sense, since it holds sense of the term only, since it sustains no relations whatever with the external no relations to the external world. It is world. On this account, it can never be not an animal until it does. an animal. The above views were published by me in a memoir, presented to the Amer. Acad, of Arts and Sciences, July 1851 : Researches on the Origin, Mode of Development, and Nature of the Spermatic Particles among the Four Classes of Vertebrated Animals. Note. — In the foregoing account of the morphological relations of the spermatic particles as cell products, nothing was said relative to analogous phenomena in the vegetable kingdom. The subject of the existence of true spermatic particles in plants has been such a mooted one, that I did not think proper to introduce it in the text. But for my own part, I believe that, as to morphological conditions, the phenomena of reproduction in the animal and the vegetable kingdoms, are analogous throughout. In the study of nature we must not let names confuse our ideas of things ; and, call them what you will, I think there is no doubt that there are in plants particles for fecunda- tion, exactly corresponding to the spermatic particles in animals. The doctrine of vege- table spermatic particles has been treated with ridicule by Schleiden (Principal of Scien- tific Botany, &c., translated by Lankester, London, 1849, pp. 99, 359) ; but aside from the weight of analogy, recent investigations have shown that it is not so easily disposed of. Without discussing the subject historically, I will allude first to the remarkable memoir of Kobin, on the existence of an ovum, as well in the male as in the female of plants and animals ; producing in the one case spermatozoa, and in the other the primitive cells of the embryo ; see Compt. Rend. 1849. The object of this memoir is to show the com- explosion of this view, besides otherwise treating the subject in a very profoundly physiological manner. They have figured and described many forms, and given the whole subject an individuality it never can lose. But by far the most comprehensive article that has appeared on the subject of the spermatic particles, is that of Wagner and Luckardt, in the Cyclopoed. of Anat. and Physiol. Art. Semen. ITS PHYSIOLOGY AND PATHOLOGY, 745 plete morphological identity of the male and female reproductive primordia, through- out all organized forma. Not only are the cell-phenomena of the male and female products of the same kingdom identical morphologically, hut also of the same sexes of the different kingdoms. Leaving out the weight of analogy, A priori, the observed processes of cell life clearly indicate that there are in plants male particles of fecunda- tion corresponding to the spermatic particles with animals. These are the pollen-grains with the phanerogamia, and the contents of the ajitheridia with the cryptogamia. See, for a farther consideration of this subject, a memoir of Thuret on the anthers of Chara, &o. Ann. d. Sc. Nat. 3dv. p. 65, but especially the work of Hofmeister, " Verg- leichende Untersuchungen der Keimung, Entfaltung und Fruchtbildung hoherer Kryp- togamen, und der Saameubildung der Coniferen.'' Leipzig, 1851. Cilia. — We now come to the consideration of another part of our subject, of the products of epithelial cells. I refer to the formation of cilia; and although it is not, it is true, an endogenous production of cells, like those we have just considered, yet its discussion cannot be better taken up than in this connection. These cilia are solely the product of epithelial cells, and give to those on which they are found, a function different from that of the true secerning organ. They are minute teat-like processes of the cell-membrane, capable of moving backward and forward, and there- fore have a waving oscillatory motion. These cilia exist on the epithelial cells of those membranes which have an external outlet, and therefore may there be regarded as truly excretory organs ; for by this oscillatory movement towards the external opening, they are able to convey an astonishing amount of material. As bearing out the homology of the epithelial cell, and the ovum, they are found existing on the surface of the latter, especially among the Mollusks and Radiates ; and here their potency as organs of locomotion cannot be appreciated, unless one has studied these lower forms, for they really constitute the active agents of their life and motion. When existing on cells, they are upon one of its surfaces only, studding its crown, or the part opposite that by which the cell is attached to the basement-membrane. When existing upon ova, they generally cover its entire surface. Their formation upon epi- X Fig. 35. # if Formation of Cilia from Mucous Memlarane of Frog {Sana pipiem). u. A cylindrical epithelial cell, the upper portion of which presents a bulging, h. The same, still farther progressed, c. This " bulged" portion beginning to split, d. Cella on which this splitting has taken placoj forming cilia. VOL. VI. — 48 746 THE cell: thelial cells, I have had the good fortune to observe, and their gene- sis here may be considered as an expression of their formation every- •where. A nucleated epithelial cell exists upon a mucous membrane ; if cilia are to be formed from it, it lengthens and becomes somewhat cylindrical in shape. A part of the end which is free then becomes a little constricted, or partially separated from the rest, as though a minute thread had been drawn around it. This constricted portion is the part out of which the cilia are to be formed. It then divides into fasciculi, each of which splits up into cilia.* The formation of cilia, therefore, is only the splitting up of a por- tion of a cell into filaments. But, on the other hand, there is reason to believe that each of these cilia is tubular ; in other words, hollow like the finger of a glove. If this is true (and I can assure any one that it is a point exceedingly diificult to settle definitely), there is a de- ception in the appearances presented ; for they then must be regarded as ex vaginations of the cell- wall, or the pushing out of teat-like pro- cesses from its surface ; and this could well take place in that con- stricted portion which I have described.f But this is a point need- ing much more study and attention. However, from what I have really observed, I must, for the present at least, regard cilia as digital portions of cell-memhrane. They therefore should have the capacity of cell-membranes; and when this is fully considered, it can cause no wonder that all the varieties of motions here observed should be alone due to the intrinsic power of the cells themselves, and without the agency of those tissues by which similar phenomena in higher and more compound life are necessarily connected. Lasso-celU, or the tactile and prehensile cells on the surfaces of Medusse. — It may seem somewhat strange that I should include these cells under the head of epithelia. But, from a somewhat careful study I have of late given them, I am inclined to the opinion that, histologically, this is their nature. And as such, a consideration of * The obserratioES of KoUiker are exactly to the same effect. His investigations were made upon the epithelial cells of the oviduct of Planorbis oorneus ; vide Beitrage zur Kenntniss, &c. Berlin, 1840, p. 33, pi. i. fig. 12. My own observations were made upon epithelia of the mucous membranes of Batrachians. t For farther details on this interesting subject, I may refer to a paper published some years since. See Histological Researches on the Development, Natm-e, and Function of Epithelial Structures, Amer. Journ. of Med. Sci. N. S. vol. xx. p. 70. ITS PHYSIOLOGY AND PATHOLOGY. 747 their products may be properly introduced here. Even were this last not true, I do not think I could well desist giving them here a careful review, on account of the many beautiful phenomena pre- sented. And without forestalling my subject, I may say that the studies I have made of these lasso-cells have been to me a source of more delight, and has given me a broader view of the signification of ele- mentary forms, than any other of equal magnitude I have ever taken up. By lasso-cells, I mean a kind of cell which is found upon the body, and especially upon the tentacles of the Polypi and Acalephse, as well also as upon some of the Mollusca, and which also exist upon the external surface of many .of the internal organs. These cells are generally of an oblong oval shape, of a variable size, and contain in their interior a long filament coiled up upon itself. This filament is thrown out, and thereby serves as a prehensile organ by winding around the minute object to be caught. This cell is attached by one surface, one of its short diameters, and from the other extremity, the filament passes out. This filament is a part and parcel of the cell, a continuation of its membrane by a slender tube coiled up in the interior ; its expulsion, therefore, is by its inversion, or a turning inside out. In other words, and per- haps expressing it more clearly, the whole is a cell, which has a long process of itself extending into its interior, and which is thrown out by inversion, exactly as may be a finger of a glove. But to look at the subject a little more particularly. This fila- ment is a very delicate tube, and has upon its surface, as observed when out of the cell, numerous little barbed points, which are arranged somewhat regularly, and all of which point backward towards the cell. However long and delicate this filament may be, these barbed points exist to its very extremity. This is a point which does not appear to have been before recognized, and which I did not perceive myself until quite recently, when working with con- densed light. There appear to be two varieties of these cells ; first, those containing nothing but the tube, and which, as such, connect with the cell ; and second, those into which there is a kind of stigma, or stock, from which the filament proceeds, and which is the bond of connection between it and the cell. This stigma is about twice the size of the thread, has a somewhat ventricose shape, and, like the tube, has numerous points. It is of course inverted in being thrown out. Another diiference between these two kinds of cells, is, that 748 THE cell: with the stigmated ones the thread is rather short, say from ten to fifteen times the length of the cell, while in those not stigmated the thread is very long, and often sixty to eighty times that of the cell. That this slender tube is thrown out by a process of inversion, is proved by watching it, as Prof. Agassiz and myself have repeatedly done, and also by the fact that, when in the cell and coiled up, the barbed points on the thread, and especially upon the stigma, where they may be well seen, point forward, or, rather, in the opposite direction to what they do when it is uncoiled. The beautiful design in these barbed points upon this thread cannot fail to strike us with admiration; for, pointing backward, they serve well to retain the ob- ject around which the thread is thrown. These cells are truly pre- hensile organs, and in handling these animals, it is from them that the itching, nettling sensation is produced, and in some of the Acti- nia they are so large that you can feel the threads on your finger. These coarser forms, however, are not the ones in which these phenomena of the lasso-thread can be best studied, but with the coral polypi {Astrangse Dance, Ag.) they can be most thoroughly made out. But before I proceed any farther, I will refer for a moment to the history of these forms, that we may see what has hitherto been known on this subject. Wagner* appears to have been the first to notice them with the Actinia, and he has described them as spermatozoa. Subsequently, they were studied by Erdl,t who traced their presence in other genera, and described some of their peculiari- ties. QuartrefagesJ also observed and carefully figured them. In the same way they have been noticed by Siebold.§ With the excep- tion of Wagner, all these authors regarded them as prehensile organs, serving to seize upon and secure their food. However, all their more minute and more beautiful relations were not known, and this part of the subject has been recently taken up by Professor Agassiz,|| who has quite exhausted it ; and, in so doing, has brought into notice phenomena and physical peculiarities which, in point of beauty, have, I think, no equal in the whole department of histology. * Wagner ; Wiegmann's Arohiv, 1835, ii. p. 215, pi. iii. fig. 7. t Erdl ; Miiller's Arohiv, 1841, p. 423, pi. xv. figs. 3, 6, 8, 9. t Quartrefages ; Anna!, des Sc. Nat. xTiii. 1842, p. 81, pi. ii, figs. 4, 6. ? Siebold ; Comparative Anatomy, transl. by Burnett, vol. i. g 28. II Agassiz ; From a forthcoming memoir on the coral polyps, to be published by the Smithsonian Institution ; but see especiaUy some notes to the translation of Siebold and Stannius's Comparative Anatomy, | 28. Agassiz's drawings are unsurpassed. ITS PHYSIOLOGY AND PATHOLOGY. 749 When such is the condition of the subject, it might 'well be re- garded as out of taste for me to take it up with any pretensions for its farther elucidation. But it has been my good fortune to make out clearly many points hitherto obscure ; this success, how- ever, I attribute to my superior instrument and some other advan- tageous means for investigation. I have already mentioned the anatomical points which I have made out for myself; we will now refer to the genesis of this body, as I have had the good fortune to observe it. It exists, first, as a small sphere, in fact, a cell (and an epithelial one too, I think), having probably the same mode of pri- mary formation as other epithelial cells. Gradually, it assumes an oblong shape, and has a dark-lined appearance in the centre. This, I think, is the nucleus, or at least is dark granular matter occupying the central portion of the cell. At the next stage, you perceive the spiral thread or tube faintly appearing in a spiral condition, and, as the Laaso-oellB and their formation, a. Cells of the s^nple kind with coil inside, b. The cell being dis- BoWed by acid, the coil is left unharmed, o. Cells of the stigmated kind, the barbs on the stigma seen to point downward, d. The same, with the lasso thrown out, the barbs on the stigma pointing upward, the whole having been everted, e. Cells of the simple kind with laiiso thrown out, the lasso being very long. In both kinds the lasso is barbed throughout, and so flue that no pen can mark them. /. The formation of lasso by deposition of granular matter on inner surface. — ^Prom Astrangae Danae. 750 THE cell: cell increases, so this thread increases likewise, and becomes more and more distinct until fully formed, when the transparency of the cell- wall allows it to be seen most perfectly. It then appears coiled in a very perfect manner, the width of each coil being about that of the short diameter of the cell. It would therefore appear that the nucleus is the starting-point at which the formation of this tube commences. In the stigmated variety it persists to a certain extent on its original form, but in the other kind it is entirely metamor- phosed into the tube. This may account, in part, for the greater length of tube in the latter than in the former. In my opinion, this tube is formed by a spiral deposition of matter on the inner surface of the cell, exactly like the formation of the spiral vessels or threads in vegetable cells by the deposition of cellulose. Not only is this view supported by analogy, but also from the fact that the formation, when first occurring, is invisible, being probably finely granular albu- minous matter, exactly as is true of cellulose in the vegetable cell. Farthermore, the formation of the spiral threads in vegetables is of nuclear origin, and such we have seen to be the case with these cells. It is true that the filament is solid and not tubular in the vegeta- ble cell, neither has it any connection with the cell-wall by conti- nuity. But this fact does not invalidate the view I have taken; for if a long fibre is to be formed inside of a .cell, and to be capable of being projected from it, and yet retain its connection with the cell, it is difficult to conceive how the formation could have been otherwise ; and as the very first phenomena are invisible, it seems proper that we should explain them on the grounds of analogy. But it may be asked, what is the signification of all this ? As it appears to me, it is this : You have here an endogenously formed cilium ; in other words, one form of a ciliated epithelial cell, having a single cilium which is formed inside of the cell instead of outside, as is the case with ordinary ciliated cells ; for, the cilia on common cells we have seen to be only external protrusions of the cell-wall, while in the present case, it is, in one sense, an internal protrusion. This well accords also with the idea of its true epithelial character, which we have asserted on other grounds.* * I am not yet fully determined as to the morphological relations between these lasso-cells with their filament, in animals, and the cells with spiral formations, in plants. There is, however, this difference in the outset, as to the structure of the filament. We have seen it to be tubular with the lasso-cells, but in plants it is not hollow but solid, and has a cu-cular, an eUiptic, or a quadrangular section. Moreover, there is ITS PHYSIOLOGY AND PATHOLOGY. 751 The spiral, in all my examinations, has invariably been from the left to the right. Thus formed, it is ready to be thrown out, and this projection takes place in the following manner : By some irrita- tion of the cell, probably altering the endosmotic condition of its membrane, there is tendency to expel its contents ; and, as I have before said, the filament is thrown out by being everted. This is accomplished so quickly as to almost entirely escape the vision, and when all run out, the whole has the aspect of a sac-like body, into which is inserted a long delicate tube. It may be asked if the barbed points experience this eversion in like manner? My opinion is that they do not; and I base this upon the fact that, when the tube is coiled, they occupy an inverse relative position to the one when uncoiled. They would, therefore, be formations in the tube rather than upon it.* By way of conclusion, I will add that when one sees a tube, the whole thickness of which is not more than j^J^^j of an inch, and whose walls are studded with fine and regularly arranged points, and also having a delicacy so great that the whole is capable of being almost instantly turned inside out, he naturally views with wonder the almost infinite plasticity of animal membranes, and his mind is so opened to the wondrous capability of organized forms, that there no evidence that these filaments in vegetable cells are the result of an internal protru- sion of the cell-wall, but they appear to be rather the result of a granular deposit on its internal surface. These remarks apply to the common " spiral vessels," as they are called. But the spiral fibres observed in the Antheridia of Charas, Mosses, and Ferns, appear to be of a different character, and if not shown to be vegetable sperma- tozoa, may prove to be morphologically analogous to the lasso-cell contents. Upon the peculiarities of structure of the spinal fibres or vessels in plants, see Schlei- den's Principles of Scientific Botany, &c. transl. by Lankester, London, 1849, p. 42 ; Mulder; the Chem. of Verget. and Animal Physiol, transl. by Johnston, Edinb. 1849, p. 420 ; and upon the last topic (these fibres as seen in the Antheridia of Charafi, &c.) Bee a memoir of Thuret, Ann. d. Sc. Nat. xiv. p. 65, and Meyen's Physiologic, iii. p. 223. * The following are some of the genera, in all the species of which the lasso-oella may be found: Actinia, Meandrina, Manicina, Asiraas, Campanularia, Syncoryne, Coryne, Cyansea, Aurelia, Thaumatias, Tiaropsis, Hippocrene, Sarsia, the Hydroid and true Me- dusae. Without doubt, farther researches will show that very many other genera are similarly endowed. For the biography of the lasso-cells, see, beside the authors already quoted : Wagner, Icon. Zoot. tab. xxxiii. figs. 8, 10, 11, A, B, C. ; also in Wiegmann's Arch. 1841, i. p. 39; Ehrenberg, Wiegmann's Arch. 1841, i. p. 71, tab. iii. ; Kolliker, Beitr. zur Kenntniss d. Gesohlichts, v. &o. p. 41 ; Milne Edwards, Ann. d. Sc. Nat. xvi. p. 223, pL viii. fig. 9 ; PhiUppi, MuUer's Arch. 1843, p. 62, tab. v. fig. 9 ; and Will, Horse tergestinse, &o. pp. 79, 81, tab. ii. figs. 23-25. 752 THE cell: ensues a train of reflection, than which nothing can be more service- able or conducive for his broadest comprehension of physiological science. II. Chyle and Blood-Cell Function. In the somewhat extended remarks on the genesis of these cells, there was necessarily included some statement of their function. This, however, was not definite, and the importance of the subject demands that it should be considered under a separate section. We have seen that there are various and widely dissimilar opinions as to their genesis. A still greater want of uniformity exists as to opinions of their function. At first, it certainly appears singular that the use of so common a product should remain so long not definitely and indis- putably settled. But those who have been at all engaged on these subjects know full well the difiSculties attending their satisfactory study. However, I think there are now sufficient data for a safe and legitimate conclusion respecting this matter. In order that the full idea of the subject may be embodied in one consideration, I shall run over the ground in a somewhat comprehensive manner. We have seen on a preceding page that the nutritive circulating fluid has a rank quite corresponding to that of the animal in which it is found. In the Radiata, it appears little else than the triturated food, from which the nutritive portions are extracted more by pres- sure than by solution, for there is no elaboration except that of simple division. The circulating nutritive material is only chyme, and these animals cannot be said to have any blood. Among the remaining Invertebrates a special elaboration takes place ; for, beside the oral trituration there is a digestion, and the nutritive liquid is the result of this last. It has a higher character, which is expressed in the presence of corpuscles. In a low sense of the term, these animals can be said to have blood, but this blood is only chyle in circulation. As we pass from the Invertebrata to the Vertebrata, an additional element is intro- duced, for not only does the circulating liquid have chyle, but true blood also ; and which last they have, not because they are verte- brates, but because they are of a higher type of structure, and de- mand a more extended nutrition. On a preceding page, I have given the reasons why we should re- gard the white corpuscle of the blood of vertebrates, and the common corpuscle of the blood of the invertebrates, as analogues (not homo- ITS PHYSIOLOGY AND PATHOLOGY. 753 logues) of each other. The coloured corpuscle belongs to the Verte- brata alone.* It is asked what is its use ? The answer to this question includes that of all the corpuscles of the blood ; and a very natural way of seeking it, is by consideration of the difference of the nutritive phenomena in these two grand divisions of the animal kingdom. This difference consists in the amount and extent of the oxygen- ation of the tissues. The relations of this oxygenation to tissue are mostly those of a vitalizing character. Among the invertebrata, the simple function of nutrition, or the adding of plastic material to be elaborated by the tissues, is performed by the circulatory system, simple as it is : while the conveying of oxygen is accomplished by another app'aratus, which of itself has as wide or even a wider dis- semination than the former. But with such a plan the oxygena- tion cannot be very thorough and minute. The general structure of the vertebrates, on the other hand, does not readily admit of a similar arrangement, and even if it did, it could not meet the activity of their functions, which demand a more minutely distributed form of nutri- tion and oxygenation. This is accomplished by the nutritive and oxygenating systems being contained in one, so that whenever there is borne the means of nutrition, there is also borne those of oxygen- ation and vitalization. This general statement prepares us for the view which we are about to take ; that it is quite natural that such a circulatory liquid should possess two elements, viz. : 1st, those of simple nutrition, consisting of the plasma and the colourless corpus- cles ; and, 2d, those of oxygenation, consisting of the coloured cor- puscles. Now, if we are led to adopt this view, from a survey of the nutri- tive functions as occurring in invertebrate animals, we find it con- firmed by an analysis of the phenomena met with in all the higher forms. Thus, in the lowest vertebrates, which seem to exist on * I scarcely need mention that when coloured blood is met with among the Inverte- brata, the colouring matter is in the plasma and not in the corpuscles. Such is true of many of the Annelida, where the corpuscles have the same pale, granulated aspect as in the Insect^. Moreover, this colouring matter seems to hold other than necessary relations with this liquid, for Milne Edwards (Annal. des Sc. Nat. tom. i.. p. 197) has shown that there are Nemertiui having colourless blood. I cannot regard the observation of Wagner {Zwr vergleich Physiol, d. Blutes, pt. i. p. 8) as correct, when he alleges that he has seen real red corpuscles in Terebella. Both Leeuwenhoek and Hewson seem to have laboured under a similar mistake in regard to the blood of grasshoppers and larvse. (See Hewson'a Works, 8yd. Soc. ed. p. 234.) 754 THE cell: the confines of the two kingdoms, the mjxinoid fishes, and with ■which oxygenation is very feeble, and almost wanting, the coloured corpuscles are few.* As we pass up the scale the same relation exists. Thus, in the class of birds, which, from the relations they sustain with the external world, have a vitality of the tissues generally not exceeded by that of any other animal in the whole animal kingdom, giving them the greatest amount of strength and agility with the least weight ; in these, you find the largest number of coloured corpuscles. In man, we notice the vitality and elasticity of his whole system in proportion to the amount of red or coloured corpuscles in his blood. We cannot, therefore, resist the conclusion that the coloured cor- puscles are necessarily connected with the process of respiration or vitalization by oxygen, of the tissues — in fact, are the oxygen-car- riers, the travelling respiratory organs of this division of the animal kingdom.- This conclusion, thus arrived at, is supported by the following facts, of the truth of which any one may easily satisfy himself: — Dark blood both in and out of the system assumes a lively reddish hue upon being exposed to oxygen, and at the same time carbonic acid is disengaged. The mere serum, which contains no corpuscles, has none of these phenomena. The consumption of oxygen and the disengagement of carbonic, acid is in direct ratio with the amount of corpuscles.f In the embryo, as we have already seen, these corpuscles are not coloured until they come in contact with the air directly or indirectly ; we may therefore regard their red colour as consequent in some way upon their condition as oxygenizers ; a fact borne out by all the phe- nomena of respiration and nutrition with which we are acquainted.! The immediate cause of this colour we know very well to be the pre- sence of a chemical constituent called hsematin ; but why this should be red instead of blue, no chemistry has yet been able to decide. I • Vide Yarrell, History of Britisli Fishes, London, 1836, vol. il. p. 468. f Simon's Chemistry of Man, Sydenh. Soo. ed. vol. i. p. 154. } Simon (Chemistry of Man, Sydenh. Soo. ed. vol. 1. p. 120) speaks of hlood-oor- pusoles being found in the thoracic duct of rabbits and horses. Thus apparently showing that these corpuscles become red before they enter the lungs. But I cannot regard such facts as at all influencing the truth of the opinion I have above expressed, for it is quite probable that these corpuscles were here extravasated. Thus, Dr. Davy (quoted in Hewson's Works, Syd. Soc. edition, by Gulliver, p. 277) found a small portion of red crassamentum in the thoracic duct of a man who died suddenly of apoplexy. ITS PHYSIOLOGY AND PATHOLOGY. 755 think it pretty well decided that this colour exists in the cell liquid, and not in the membrane. When these corpuscles thus formed are brought in contact with the air, their reddish tint becomes more pronounced, which is probably due to some chemical change in the hsematin. They then absorb oxygen in virtue of their being cells, and thus laden they carry it into all the vascular tissues, and receive in return carbonic acid, which appears to displace the former. This rotation of function may give rise to that change in their form mentioned by Mulder,* viz. that the corpuscles of arterial blood are hi-concave, while those of venous blood are bi-convex. These phenomena, however, I have not seen, and it appears to me to be a most difficult subject of microsco- pical research ; for the moment venous blood is exposed to the air, as being put under a microscope, it becomes arterial. After all, it may be remarked that, in the present state of our knowledge, it is as difficult as it is hazardous to form any con- clusions upon the causes of all the differences between arterial and venous blood. This much, however, I consider well established, that the red corpuscles are intimately connected with tissue respiration, and I shall here briefly state their function, as being that of the vitali' zation of tissues, which are constantly experiencing the metamorphosis of life. This metamorphosis involves two prominent phenomena, the consumption of oxygen, and the elimination of carbonic acid ; all of which is performed by the agency of the coloured corpuscle."^ * Mulder ; Chemistry of Animal and Vegetable Physiology, translated by Johnston, p. 342. f I scarcely need say, that a variety of opinions have been entertained as to the function of the coloured blood-oell. Wagner,* Henle,| Wharton Jones, J and Newport,^ regard them as the elaborators of the fibrin ; in fact, give them that function which I have ascribed to the white corpuscles. But, this view appears to me quite untenable for several reasons. In the first place, fibrin is undoubtedly formed in the chyle, and in which no coloured cells exist. Then, again, in inflammation, the amount of fibrin is increased, without an increase (on the other hand, there is rather a diminution) of the coloured cells. The opinion of Mulder|| is even still different. He regards their function the pro- duction of an oxy-protein compound ; for, he affirms that the blood-corpuscles are really surrounded with an envelop of oxide of protein, in the lungs. But these views, based upon chemical data almost exclusively, have not been generally received with &vour. As for myself, I do not feel competent to discuss them. * Wagnor ; Physiology, tranalated by Willis, p. 448. f Henle; Trait§ d'Anat. gfinfiraloj &c. torn. i. p. 457, d seq. I Jonea ; Brit, and For. Med. Rev. xiv. p. 597. J Newport; Proceed. Eoy. Soc. Feb. 6, 1845. n Mulder; Chemistry of Animal and Vegetable Physiology, translated by Johnston, p. 332, ei sec[. 756 THE CELL: We have thus considered the blood-corpuscle as discharging a function as a simple individual cell, but there is one other point of its use which should be briefly referred to in this connection. I refer to the immediate transformation of these corpuscles into compound tissues. That this sometimes did occur, or in fact was the means by which tissues in general were formed, was long ago entertained by Martin Barry.* But the data, on which this opinion was founded have not since been verified. Since then, the observations of Dr. Zwicky,t upon the metamorphoses of the thrombus, go to show that blood possesses the power of becoming organized and developing itself into a tissue. I have not studied the subject of the phenomena to which Dr. Zwicky alludes, but some appearances I have observed in the blood of Amphibia show me that it may be transformed into a fibrillated tissue ; but whether it is to be regarded a normal or ab- normal condition, I cannot say. Thus, the blood of frogs will often show these changes : At first, the corpuscles are floating about, or lying in a loose irregular manner in the field ; next, they begin to arrange themselves in a linear series ; then, a coalescence of the cor- puscles take place, giving the tube a wavy outline on each side ; this last finally disappears, and there appears then a more or less smooth fibrilla. The blood thus changed has a fibrillated, tough feel and structure. This, however, may be a function of reserve in nature, to meet the accidents of the life of tissues ; but such phenomena are not involved in the ordinary round of nutritive action, as will here- after be fully shown. Fig. 37. Blood of Frog, undergoing a kind of organization, a. Blood-globvdea arranged in a linear scries, i and c The same, changing into fibrillK by flattening and lengthening, d. Arranged into fibrillse, forming a fibrillated tissue. It now remains for us to inquire the function and use of the white or colourless corpuscles found in the blood. We have already seen * Barry; Pliilos. Transact. 1840, p. 601. t Zwioky; Die Metamorphose des Thrombus, Berlin, 1845. ITS PHYSIOLOGY AND PATHOLOGY. 757 that they are formed in the nutritive liquid which is derived from the food. And as formations of this kind I have heen inclined to regard them, in both a physical and teleological point of view. Physically, they are the individual expressions of the formative power of that liquid in which they are found ; and as such fibrin necessarily enters a good deal into their constitution, therefore, in this respect, they may be regarded as the organized fibrinous parts of the lymph — constitut- ing the vehicle of fibrin in the blood — the elaborators of fibrin. On the other hand, teleologically, they hold certain future relations with that higher form of blood-cell, the coloured corpuscle. Chemistry has proved that the nucleus of this last is mainly composed of fibrin, and my preceding observations have shown us that it is around this white corpuscle, as a whole, or in part, or its analogue, that the coloured cell is formed. Thus, in the oviparous vertebrates, we have seen that the whole corpuscle serves as the nucleus of the coloured cell ; while in the mammalian it is the elaborated product of this corpuscle, or its nuclei, which serves the same purpose. This opinion of the function of the white corpuscles, which is based entirely upon a genetic and physiological view of the subject, finds its support in pathological phenomena. Thus, in inflammation, as the investigations of Andral and Gavarret* have shown, the quantity of fibrin is increased, and this increase is attended with a correspond- ing increase in the number of white corpuscles, but without an increase of the coloured cells. This I have repeatedly witnessed myself. But whether this abnormal condition of the blood constituents can be said to be due to an excess of fibrin per se, or to a want of its ultimate elaboration through the vitalizing agency of the coloured corpuscle, I do not know. But this much is certain, that when tissues begin to be inflamed their bloodvessels contain an excess of white corpuscles. f And when a large viscus, like a lung, is inflamed, this peculiarity be- comes general, nearly all the chyle-corpuscles seeming to remain as such in the blood plasma. These abnormal blood conditions will be more fully discussed here- after, in their proper place. I shall briefly state the function of the lymph- corpuscles to be — To elaborate fibrin from the chyle plasma, and, at the same time, serving, either in whole or as parts, for the bases of the coloured cells, * Andral and Gavarret; Keoherches sur les modifications de proportions de quel- ques principes du sang dans les Maladies, Paris, 1842. j- But this condition of things is due to general relations of the blood instead of local ones, a? we shall hereafter perceive. 758 THE cell: III. Neeve-Cell Function. The nervous tissue, taken as a whole, is both the originator and distributer of mental force. In the higher animals, its existence is necessary for what may be called mental manifestations ; or, in other words, it is the tissue alone in and by which such forces are manifested. But in some of the lowest of the invertebrates this is not true, for in them no nervous system can be detected ; yet they have motions as varied and adaptive as others of the same class, which have true nervous tissue. The distribution of the nervous forces be!?ngs to the tubular por- tion of this tissue, which has little other than mechanical relations ; we shall not need, therefore, to allude to this part of the subject, but our attention will be directed to the cells themselves. I scarcely need say that the nerve-cells are the producers of nerve- force, and that by them or their analogues, alone, it is eliminated. They are, moreover, to be regarded as the terminal, and not as the transitionary conditions of this tissue as an active one. By their agency, and probably acting as do other cells, viz. by endosmose and exosmose, the nervous power is eliminated ; and it is their pro- perty to in some way produce this, just as it is the property of another cell to secrete milk. In a mere potential point of view the one instance is just as easily comprehended by the mind as the other. Beyond this I may safely say we know nothing, for here is the end of true physiology. It is certainly the highest phi- *4osophy that teaches us that there are boundaries to our knowledge even of the simplest things. We must learn of what cannot be known. Even were thought, as a cell-product, just as materially expressed as is milk or saliva, should we then know any more about the matter ? We see an image on the retina, and the act of seeing is thus visibly demonstrated ; but after all, material as it is, does it in the least explain vision ? We have already seen that the layer of retina, exposed to the image, is composed of cells ; yet as such they receive and conduct an immaterial something to the sensorium. This is a fact which we can appreciate, and which is well settled, but it explains nothing. We can as well conceive that material cells should eliminate immaterial forces as that they should receive immaterial images. ITS PHYSIOLOGY AND PATHOLOaY. 759 CHAPTER V. RETROSPECTIVE VIEW OF CELL-LIFE. The preceding account may be said to constitute a biographical sketch of cells in all their conditions of life. This has necessarily been a matter of detail, and we have scarcely paused in our course to consider the nature of the processes under description. In bringing the physiological part ();? our subject to a clo|e, I have thought proper to take a survey of the whole matter, that we might learn the signi- fication of cells in physiological science. This I shall do in as brief manner as possible. The great outstanding fact, which appears be- fore us as the result of these studies, is, that there is a fundamental unity of all organization. This we have seen to consist in elementary particles, which in both animals and plants are formed upon a com- mon plan. It was the opinion of Schwann and Schleiden, who truly originated this view, that this common plan consisted in the pre-existence of a solid, fundamental body (the nucleus), around which is formed a membrane, ultimately expanding and constituting the cell. It has been one of my objects, in the preceding pages, not to show that this view was not founded in fact, but to show that there could not be claimed for it an universality of application. This I hoped to accomplish by an attempt to demonstrate another principle of formation ; which is, that the fundamental idea of a cell is a simple vesicle, and that a nucleated cell is simply one vesicle containing another within its walls. With this view, the nucleus and cell are identical in nature, and this gives to the whole doctrine a unity quite wanting with any other view. For, according to Schwann, the nucleus and cell possess dissimilar natures. With Schwann, the nucleus is exogenous and germinative ; with me, the nucleus is endogenous and reproductive. The difference between our views cannot perhaps be better and more briefly stated, and by those familiar with this class of phenomena it will be understood. It is not for me here to recapitulate the grounds on which this view is founded, for I could not more briefly state them than I have done. The mind so naturally seeks a unity in nature, and especially in the formation of an elementary fundamental part, that plurality of methods as to her workings may of itself be almost considered as an argument against the correctness of any of them. I have often 760 THE cell: been inclined to put that stress upon this point, as almost to lead me to believe that we do not yet understand the nature of cell-processes, and that, when we do, there will be perceived an unvarying unity, transcending in beauty and simplicity any and everything we have yet learned in organic life. Still, we must reason from what we know, and not from what we would wish ; and although this idealism of a unity should always be a conservative element in our studies of natural phenomena, we should bear in mind that it is to be ac- cepted in science only when borne out by unmistakable facts. On this account I still cling to the truth of what has been observed. In both plans of the form^jtion, or rather at the end of it, there is one feature which is alike and common. I refer to the cell being nu- cleated. This is a condition of its most perfect and adult form, which necessarily exists in virtue of its being a complete whole. In fact, I may say that, as a certain form and size is the organic perfection striven for and to be attained by animals, just so is the nucleated condition the organic perfection to be attained by cells. It is true that the view of Schwann involves this idea as well as that of my own, but not, I have often thought, with the same fulness and complete- ness. For with Schwann, the nucleus being pre-existent and form- ative, its organic agency is past when the cell has been formed around it, and then the cell is nucleated, in memory (if I may thus express myself) of its past and formative condition. But, according to my own view, the formation of the nucleus is secondary, the sought-for perfection of its adult life, the offspring of it as an organic particle in its fulness of power ; and as, in man, his perfection as an individual is expressed in that fulness and potentiality of his qualities constituting true manhood, so, in the cell, it is likewise a secondary production constituting its nucleated character. But after all these discussions, the cell, as it appears to us — a material elementary particle — has an invariable physiological signi- fication. However produced, it is the culminating point of organiza- tion ; and if I may, upon so plain a subject, use a metaphor, it is the ground on which life and matter meet, mutually embrace, and then go hand in hand together, but showing in their united countenances that they bear in constant memory the conditions of their first em- brace. But this is only one part of our subject ; we have only alluded to it in the light of development ; we have simply traced an organic particle to its adult condition. The actions, the " doings" of it, after having reached its prime of life, constitute the remaining portion of ITS PHYSIOLOGY AND PATHOLOGY. 761 its biography. Here, also, the same tendency towards a fundamental unity of action is manifested. We have seen that, although the statement that all tissues take their origin from cells is not true to the letter, yet it is correct ac- cording to the true philosophy of the subject. Thus, we have learned that some tissues are formed from granules or utricles, and not from nucleated cells ; but at the same time it was shown that the significa- tion of these utricles is the same as that of cells. It may be truly said that the fundamental phenomena attending the appearance of organized structures is always the same, that is, cellular. The more immediate grounds of this opinion need not here be reviewed. The experience on which it is baged is as authentic as any we possess of other phenomena of the external world. The two conclusions of these studies of cell-life are, then, 1. The existence of an elementary particle, having an invariable unity of expression, the cell. 2. The universality of the application of this particle for the formation of organized parts, tissue. The philosophic mind cannot conceive of two results connected with the material world, which come home to it with more significant truth and beauty. For experience has here taught and made manifest to us, that which the highest philosophy has always prophesied — simple unity amid ever varied diversity/. VOL. VI. — 49 762 THE cell: PART II. PATHOLOGY. CHAPTER I. INTRODUCTORY. The domain which we have just left, Physiology, is by no means so widely separated from the one upon whic*h we now enter, Patholo- gy, as might be supposed from the commonly received doctrines of medical science. I do not make this remark, however, as applicable to anything but their material expressions. For the difference as to essential nature between truly normal and abnormal phenomena, must of course be wide. But in our conversation with the material world, either natural or unnatural, we can learn about it only through the intervention of material forms. It is in this way that we have learned all that we truly know in physiology, and it is in this way that we are now to inquire into pathology. And if from the minute character of our inquiries, the expectation is raised that thereby will be solved the mystery of the intimate nature of disease, that expectation will certainly remain unfulfilled and disappointed. In a general way, it may be said that pathology is but an erring physio- logy. This expresses a great deal that is true of its nature, and al- though perhaps not the whole truth, it approximates so closely, that it will serve as the basis of our inquiries. Such a view is well calculated to remove from the mind many er- roneous notions ; one of which, for instance, is, that disease is a self- existing entity, which view, if well entertained, cannot but impede our correct interpretation of its phenomena ; for we shall be constantly struggling between a fancy and a fact. Then, again, the ideas which we have of health and disease must be relative, since we have no positive data by which the one can be determined in' contradistinc- ITS PHYSIOLOGY AND PATHOLOGY. 763 tion to the other. Our conception of normal life must be extremely indefinite, and especially so, since the steps of its transition to that which is abnormal have not been well made out. Another question which arises at the outset is, does disease always have a material expression, and that too of a corresponding and inva- riable character ? • A negative answer to this would be deemed by many as quite un- physical, not to say unscientific; but in the present state of our knowledge I must regard it as by far the most correct ; for we are to reason from what we know ; and although analogy is of great ser- vice in such matters, yet we cannot be too careful of its use. We should very naturally say that, in virtue of the great fact constantly before us, viz. that vitality has its expression only in organization, which is tangible and capable of being analyzed, so should we always have a tangible expression of any perversion of that vitality. This may be seemingly very scientific, but at present it is so only nega- tively ; for there are many transitory morbid changes of the vital phenomena, many morbid conditions known by the name of functional, which leave no traces in the matter or organs in which they occur, at least as far as we can now detect, by the most indefatigable re- search. Too high an estimate must not, therefore, be placed upon these intimate microscopical studies of pathological conditions and pheno- mena. In the first place, with all the material product at our com- mand which we could ask, we must expect to know of disease only conditionally ; and in the second place, we must not be surprised to meet with many of the best expressed pathological phenomena hold- ing apparently no corresponding material relations. If these two points be well borne in mind, much error and confu- sion will be avoided. But let us return to our original proposition: Pathology' is only an erring physiology. We can understand from this, why the genesis and general laws of pathological cells should be the same precisely as those of phy- siology. And I make here this general statement, founded upon a pretty widely extended observation, that, both as to their genesis and general aspect as cells, those which belong to abnormal cannot be distinguished from those belonging to normal conditions of life. The genetic and general relations of cells in physiology and patholo- gy are, therefore, the same. But the bifurcating point in the road appears when we begin to inquire about the destiny of each. Physio- 764 THE cell: logical cells must always be considered teleologically, that is, as hav- ing relations with a future and determinate result, in the attaining of which they fulfil their destiny. With pathological cells, however, all these conditions are absent. They exist as cells in virtue of the previous existence of an abnornal formative material, which must have an organic expression of its forces. This expression is neces- sarily a cell ; but there it ends ; it sustains no higher and future re- lation for a definite result. Abnormal cells, or rather cells produced under abnormal condi- tions of life, therefore, are not characterized by any type or true individuality. I know very well that some, such as those of pus, tubercle, and cancer, have a uniformity of appearance quite remark- able, but I cannot regard this as having any teleological signification at all, but rather as due to a corresponding uniformity of condition of the abnormal plasma in which they are formed. I do not think that this view at all disparages the scientific accuracy with which they should be described. For experience has shown us that this uni- formity of abnormal plasma is so constant that it may always be counted upon in our determination of its products. With these con- siderations, founded in fact, the distinctions between physiology and pathology as based upon cells, are, therefore, not only broad, but de- finite, as far as they go. I may say, farther, that they are the only distinctions upon which we can at present insist ; remove them, and I can perceive no reason why all our pathology should not at once be resolved into physiology. It may be asked if this resolution of the two thus into one, is not desirable, as simplifying our ideas of organic life both normal and abnormal? I say no, even were it possible ; for it immediately takes away from the common pheno- mena of organic life their philosophy as manifested in their teleolo- gical bearing. Ther'e is one other result which may well be deduced from the foregoing remarks. It is, that all pathological products are neces- sarily infra formations ; they are below the standard of those of health, of which they may or may not take on some of the charac- teristics. Pathological formations may be divided into two kinds only, viz : 1. Those which simulate the type of the healthy tissues, called homosomorphous ; and 2. Those which have characteristics of their own, called heter amorphous. All abnormal products are necessarily one or the other of these kinds. It is true that the latter are most important in a practical point of view, on account of their peculiarity ITS PHYSIOLOGY AND PATHOLOGY. 765 of life, widely separated as it is from that of the normal forms. Such, for instance, are cancer, tubercle, and pus. Under the former, on the other hand, are included all those forms of tissue which are abnormal, not so much because they are dissimilar from healthy forms, but because they want very much the definite character of these last as active tissues towards a conservative, economical end in the system. They are, therefore, less- severe, and more amenable to treatment. But still, in an histological point of view, they are not the less worthy of our consideration. It is difiScult to grasp this subject unless we take it up in a par- ticular manner. Pathological products as material forms are super- ventions in and upon the healthy parts. In a causative point of view, they are therefore referable to nutrition and its perversions. And I shall take up the subject in this light, even though there is necessarily a blending of physiological with pathological phenomena. CHAPTER II. NUTRITION AND ITS PERVERSIONS THE BASIS OF PHY- SIOLOGY AND PATHOLOGY. Two conditions mark the existence of the healthy living tissue. These are, decay and refair ; the former occurring because the tissue is living — the latter, because in order to live it must preserve its physical identity. This round of actions, constituting the sum total of those making up the life of the adult tissue, has its foundation in a function which we term nutrition — a word to which, in later days, we have been inclined to give a more pregnant signification than in former times ; and this, because it thus embraces in function, either directly or indirectly, the whole phenomena of animal life. Many have thought that the relations of reproduction, or the origin and rise of the new being, should be viewed as belonging to another category of actions. But they have allowed themselves to be deceived by the importance of these processes ; for we have seen, on a preceding page, that such phenomena are only cellular, and are therefore only those of nutrition seeking an individuality of expression. Nutrition, then, being considered as the basis of physiological 766 THE cell: science, It will be my object to show that its perversions can be viewed as the foundation of our rational pathology. But that my meaning may be fully comprehended, I shall run over briefly the leading features of this nutrition as a physiological func- tion ; a task which I have omitted in the preceding pages, anticipat- ing, as I did, its consideration more properly in this connection. It is not a new, but it is a most important physiological truth, that the blood or its analogue is the source from which all the conditions of nutrition arise. It therefore follows that in it we should clearly re- cognize the elements of all these different tissues. The bloodvessels form a series of channels permeating the tissues, and terminating, as it were, in a set of vessels functionally different from either arteries or veins, the capillaries, which are the dispensers of the nutritive fluid to the tissues. And although these vessels cannot be traced mi- nutely into every tissue or part, yet their function on such tissues is always indirectly perceived. It is asked. How are these capillaries the immediate agents of this nutritive function ? It is by transuding through their parietes the hyaline plasma of the blood, into the parts through which they pass, which plasma is immediately appropriated by the contiguous tissue, or transferred by endosmosis through granular or cell-structures, to those more distant. This hyaline blastema is structureless, but it contains within itself the elements of structure. It is entirely amorphous, but it possesses in a latent form all the indi- vidualities of the different tissues. After effusion, it may serve its function as a pure plasma, by bathing the tissue, and filling the va- cancies made by liquids passed away. But this, I think, is not com- mon, and belongs almost exclusively to the sclerous tissues. It generally gives rise to more solid products. These are utricles and cells, with all their various metamorphoses. The primitive utricle appears as the first material expression, and in tissues of a purely utricular character, such as the muscular, its development does not extend beyond this point, but as such it is appropriated. But in tissues having a persistent cell-structure, these utricles pass on to cells, replacing those passing away. I believe that this hyaline plasma, immediately upon its effusion, and before the primitive utri- cles have appeared in it, is, whatever be its locality, identical in character. The reason why it has afterwards so many ultimate ex- pressions of development, appears to me to be due to another cause. It is because, directly upon its transudation, the plasma receives, in coming in contact with a tissue, the impress or type of that tissue ; so that, whatever the tissue may be, the plasma, in serving any purpose. ITS PHYSIOLOGY AND PATHOLOGY. 76T follows directly in train of the idea on which the tissue is ex- pressed. Let me illustrate this doctrine by referring, for example, to the epithelial tissue. This, as we have already seen, is composed of a layer of cells, situated upon, and attached to, a basement-membrane. The cells thus attached, whatever be their function, are constantly passing away, and must be renewed. To effect this last, a plasma is effused by the contiguous vessels. This, as soon as it comes in con- tact with this tissue, takes on its epithelial type, and the primitive utricles developed in it immediately pass on to the ulterior condition of epithelial cells. Other examples might be cited to show, in the same way, this beautiful type-power of tissues, without which the continuity of structure could not be maintained. The full apprecia- tion of this idea cannot be too strongly insisted upon ; and I will again express it in a laconic way : A liquid containing the elements of structure, upon being brought in contact with a living solid, is immediately impressed with the type-character of the latter, and, therefore, mast subserve its repair. It is not properly a selective power of the tissue, but a living act, occurring because the tissue has an individuality of its own, which it can impart. I regret that I cannot illustrate this by any reference to common examples of animal life ; but as it is one of those immaterial acts in physiology, we can appreciate it only by the recognition of the fact. I might perhaps liken it well to the act of fecundation, in which a spermatic particle, by simple contact with the ovum, impresses upon it the full type of the male parent ; and, to carry the comparison still farther, if the completeness of an individual can, in this way, be stamped upon an ovum, so, in the same way, in the act of nutrition, may the singleness of a tissue be stamped upon a hyaline plasma. I regard the recognition and application of this type-power of tissues as one of the happiest results of modern physiology, not only as illustrative of the higher tone of our present studies in this direc- tion, but also as enabling us to grasp many of the hitherto hidden forms of function in this science. • On account of its value as the hidden spring of the various nutritions, let me still farther notice its character. If it is asked, what is this type-power, I should say that its nature can be best expressed by an imperfect metaphor. It is the merhory of the immaterial idea on which a tissue is developed, still persistent during its material life. And to carry the metaphor still farther, 768 THE cell: this memory may be bright and active, or may be fast fading away, according to the age pf the tissue. The younger the tissue, the more full and complete is its individu- ality and type-power ; and if it suffers a lesion in its very early life, this breach of continuity is thereby so thoroughly repaired that its physical identity is preserved. This is the reason why in wounds with very young children, the healing of them leaves no cicatrix. The type-power extends fully and completely into the plasma effused for repair, and this repair therefore has all the character of true interstitial nutrition. As the individual advances in life, and passes into or beyond its adult period, this type-power appears to die out, or at least to lose some of its strength. This is the reason why at that time lesions are not perfectly repaired ; the material not taking on the character of the contiguous tissue, and an adventitious product occurring in the place of the lost part. The same reason may be assigned for the fact that tissues having suffered no lesion sometimes atrophy — the plasma effused not being appropriated, but, taking on a new character, may give rise to new and morbid forms. I might enter more fully into the consideration of this most inte- resting of subjects, and it would afford me much pleasure to take up its illustration in some of the most delicate tissues both in man and the lower animals. But in this place I have thought proper to sketch only its general character, which is to serve as the foundation of considerations of another character, soon to follow. It is quite necessary that we should be very familiar with this great high-road of physiology, in order that we may well know where the hy-road of pathology divides from it. Thus far, we have seen that two conditions are necessary for cor- rect and healthy nutrition ; these are, 1st. That the plasma effused shall be healthy, and such as may be fit for appropriation ; and 2d. That the type-power of the tissue to be nourished shall be sufiScient to make the appropriation. Such being the requisites of the healthy nutritive process, the perversion or suspension of one or both of these conditions gives rise to what has been justly termed abnormal nutri- tion — a state of the animal tissues which we have good reason to believe is at the very foundation of pathology. To illustrate clearly this point, we will take up separately each division. I. Perversions of the Character of the Plasma. There appears to be a law of affinity or congruity of action in tissues, which must be regarded as a very powerful conservative of ITS PHYSIOLOGY AND PATHOLOGY. 769 their integrity. By this, I mean that when the circulatory vessels do not contain the proper elements for the tissues, the latter do not call for the effusion of their plasmatic liquids ; or, to impersonate the matter, as would perhaps John Hunter, I should say that the tissues, perceiving the incongruity of the nutritive fluids, refuse to have them effused. But still, it often happens that this inappropriate plasma is effused, and then, not being at all reconcilable to the type of the tissue, yet possessing a certain vitality of its own, which perhaps is still farther urged on by the very fact of its being in contact with a living tissue, the course which it pursues is wayward, and thus we have heteromorphous pathological products. This perverted or abnormal plasma varies much as to its capacity, but is always below that of health. Its capacity is expressed in the character of its products. When quite low, granular and low cell compounds are the result. Such in fact are pus and tubercle, which appear to constitute the lowest expressions of a plasmatic formative power. When of a higher character, it gives rise to the highest pathological products, which often seem to have a kind of indi- viduality of form and function. A good example of this is seen in cancer. The heteromorphous products, then, of pus, tubercle, and cancer, I have considered as due to perversions of plasma. But perhaps the subject will come home more clearly to the mind if I say that inflam- matory products may be regarded as due to this same perversion of plasma. I do not mean to say that such products can always be traced as the results of inflammation, but as far as yet studied there appears to be here a connection, at least, showing us that when we shall know more of the matter, our most comprehensive idea of in- flammation will include ""all the conditions under which the hetero- morphous products occur. In here touching, then, upon the subject of inflammation, I shall not be considered as diverging from the main point of our discourse. I do not pretend to define inflammation, because I think we have not yet sufficient data to convey to the mind a clear idea of its cha- racter. Still, if I say that there appears to be coexistent with it, a want of healthy relation between the bloodvessels and the blood, I think I ,have stated pretty clearly all that is really known about the matter ; and even here it is very far from being certain if this absence of relation is not the flrst known effect, instead of the cause of the inflammatory process. It is, therefore, a waste of time to dwell upon that, of the nature of 770 THE cell: •which we have as yet so feeble an appreciation. We must take the results as we find them, waiting for the ultimate cause until we have more data. I have said that the first visible sign of inflammation is an absence of the healthy relation between the bloodvessels and their contents. This leads to a partial suspension of the function of both, and also causes that function which does occur to be of an abnormal char- acter. Where the processes otherwise nutritive are very active, scarce any appropriation of this plasma takes place, and the products arising in it, viz. granules and corpuscles, seem so alien to healthy tissues, that they are expelled as foreign substances. Such is pug in all its forms, and such, I think there is reason to believe, is tubercle also. When, however, the process is less active in its character, the plasma is appropriated to a certain extent ; but the tissues thus badly nou- rished, sink below their normal type, and when these conditions are kept up for any length of time, they seem to take on a character of their own. This is often seen as one of the consequences of a pre- viously acute inflammation of an organ, but especially is it observed in indolent ulcers. It is thus we see that the long-continued use of a perverted plasma, by a tissue, serves to modify the type- power of the latter. And in speaking of the minute pathology of some organs on a future page, I shall have occasion to enter more fully into the peculiarities of these changes and their consequences. It may be asked, how the etiology of cancer can be considered as belonging to the perversions of the plasma? The reply to this is that, although eminently a morbid product, it difiers widely from those of which we have just spoken, in possessing in a high degree a life of its own. The plasma in which it takes its origin, has a capa- bility not much below that of health,but still has a character as dif- ferent as the results produced. Although passing on to the higher cell-structure, its inferior character is betrayed by the objectless na- ture of its termination ; for these cells appear to be the ultimate result of a morbid action, rather than the material agents through which a higher function is to be performed. The cancerous structure, however high it may appear in an anato- mical point of view, is aimless and without function. In speaking thus of pus, tubercle, and cancer, as the results of a perverted plasma — heteromorphous products — I think I can best ex- press their mutual relations and dissimilarities if I use a figure, and say that, normal nutrition being considered the great high-road, ITS PHYSIOLOGY AND PATHOLOGY. 771 those forms of abnormal nutrition producing pus and tubercle, would be considered as small roads diverging from it, at nearly right angles. Whereas, that form producing cancer would be considered as a much larger road, diverging at a smaller angle ; in fact, often afterwards running parallel with the former. But all these diverging roads never get back upon the main one, and therefore have a termination unlike anything of true function. In concluding this section, the relations' which this perverted plasma holds to inflammation, may be thus briefly stated. We can- not conceive of this want of harmony between the action of the capillaries and the constituency of the blood, unless we suppose at the same time an exciting cause. Now, as it is true that the more we investigate minutely their conditions, the more do we find the in- flammatory process coexistent, and as, in the instances of pus and granular forms, the relations of cause and effect can be directly traced, we have a right to infer that the same is true, even when these re- lations cannot be fully made out. And so, on the whole, we seem to be justified in regarding inflam- mation, whatever is its nature, as a condition always preceding, and in all probability causing, this perversion of the efi'used plasma, and therefore the immediate cause of pathological heteromorphous pro- ducts. II. Perversions of the Type-power. We now enter upon the consideration of quite another class of phe- nomena. As the vessels are healthy and the blood normal, these phe- nomena cannot be viewed as being in the same category as those of in- flammation we have just considered. I have therefore thought proper to designate the results of such conditions as the homoeomorphous non- inflammatory products ; in fact, they are forms which, while they are really morbid, partake nevertheless of the type of the healthy tissue, as far as that condition will allow. We have just seen how, when the type-power was good and the plasma bad, the dissimilar results were referable almost entirely to the plasma. We shall now see that, where the inverse is true, the results produced have more an affinity with the tissue than with the plasma. In one sense it can scarcely be called a perversion of type-power, but rather a decrease or increase ; but, on the other hand, these words do not express the whole, for, beside these variations of amount, there is involved a pathological principle not easily or readily expressed. Suppose that, from some unknown cause, the type-power of an epithelial tissue in 772 THE cell: the body had become changed. The normal plasma is thrown out as usual, but it is not delicately and nicely appropriated as in health, and although the tissue has given it its impress, yet this is all, for the relations of size and shape appear to be absent. There therefore appears a new form which, while it bears the outward aspect of the healthy tissue, is an abnormal product ; it is, as it were, the repre- sentation of disease under the garb of health. This product is epitheloid but not epithelial. Such, for instance, is the so-called cancer of the lip, the cancer of the antrum, &c. &c. In the same category may be considered many, if not all, the hypertrophies of tissues, where a product appears with the general character of health, but with the profligacy of disease. It is not difficult for us to understand how, in some of these im- mense growths, a sufficient amount of plasma is supplied, for it appears to be a law in the nutrition of tissues that the greater the demand the greater the supply ; and so, when the demand even by a morbid product has once been made, it is furnished, and the whole may go on increasing, the vessels conforming to these changes ex- actly as though a healthy tissue was experiencing a rapid normal growth. But if we thus have products from what, in one sense, may be called an increase of type-power, constituting hypertrophy, there is quite a different class arising from a decrease, in fact a suspension of it, and which ought in this connection to be noticed. I cannot say that it is primitively of tissue origin, but, at any rate, it seems to be a dying out of the type-power ; in fact, so thoroughly is this the case that the individuality is gone, and nothing is appropriated ; and, in accordance with the law just mentioned, there seems ulti- mately to be scarce any supply, and then the tissue loses its physical identity, and gradually recedes to its primitive utricular condition. This condition of things has generally been considered in the light of an atrophy, but I have thought that it merited a distinction, and propose for it the name of Retrograde Metamorphosis. Its leading characteristics may be thus briefly stated : Bichat's definition of life, as applied to an individual, was : " The sum total of the functions by which death is resisted." Now, what applies to an individual, may be taken as, at least in part, applicable to a tissue. Its life consists in the conservation of those two conditions by which its integrity is maintained. These I have already regarded as involved in what is called nutrition — the balancing of decay and repair. Now, whatever function a part may discharge, it is necessary that it (the function) should be kept up in order that the nutrition should con- ITS PHYSIOLOGY AND PATHOLOGY. 773 tinue normal ; but when from either an unknown cause, or from a suspension of function, the part ceases to have that ever-changing vitality, then it seems to lose its type-power, and the small quantity of effused plasma is feebly appropriated, the vital cohesion of the tissue in a measure disappears ; so that although there is strictly no decomposition, yet the individuality of the part is gone, and, with it, all those forces that elevated and sustained its character above that of the primitive elements. We have, then, in place of the normal tissue, what is called a granular mass, and, as such, it cannot be re- garded as a special product, for it is the same, whether it occurs in a muscular or in a glandular organ. It consists simply of oil and albumen, uniting in their usual way. But this subject has been treated more fully in another place.* I have said that this condition differs from true atrophy ; for this last can scarcely be regarded as an ab- normal state, it being only a decrease of tissue-function, which we see daily exemplied in the muscular tissue. The same is true in an in- verse sense of true hypertrophy, which is not, as I have before said, the cause of homoeomorphous products ; — they are, both, rather variations of nutrition as to quantity than as to perversion. Such is a rapid survey of some of the perversions of nutrition which lie at the foundation of many of our best views of pathological changes. It may be asked if, under this head, may be included the causes of all pathological phenomena having their expression in a material product ? With our present knowledge, I do not think that the question can be positively answered. Nevertheless, I think I am safe in saying that the tendency of the present inquiry is to show that in abnormal nutrition is to be found the cause of all organic pathological changes. These considerations may, perhaps, serve as the groundwork of our subject; it being now our task to look into the specific character of its details. I shall, therefore, take up first the subject of hetero- morphous products — each in its proper character — commencing with the lowest. But before this, the phenomena of inflammation, as elucidated by the microscope, should be considered, and this will serve as a fitting prologue for the ensuing pages. * For its farther discussion, see an article of mine on "Tissue and its Retrograde Metamorphosis," in the Amer. Joum. of Med. So. n. s. vol. xxii. p. 22. 774 THE cell: CHAPTER III. THE MICROSCOPICAL PHENOMENA OF INFLAMMATION. I THINK that it is as true in physiology as in psychology, that the nearer we get, or, rather, think we get, upon the very elements of any phenomena in question, the more inclined are we at the same time to believe that, after all, we are mere outside spe^tat'^''--' ^ "he scene going on before us. This remark has an apt illustration it phenomena we are now about to describe. It is evident that if we are to see the real phenomena attendant upon the inflammatory process, we must study the affected tissue in situ. The tissues of nearly all the higher and warm-blooded animals do not admit of any direct experimental inquiry of this kind ; so that most of that which relates to investigations in this direction, phy- siologists have been obliged to make out froln experiments made upon such of the lower animals as have tissues of suiScient trans- parency. Some of the Batrachian reptiles have been selected for this pur- pose, and although they are objectionable on the ground that we must, even there, suppose that the same phenomena occur, under similar circumstances, in the higher animals, yet they have formed the only basis we possess of all direct inquiries of this kind.* Kalten- brunner,t in 1826, was the first to demonstrate these phenomena, and most of the physiological microscopists since have verified and carried out these inquiries. I scarcely need here describe the de- tails of these experiments, for most have read of them, and not a few seen them. However, those made within a few years have led to some change of opinion as to the real character of the phenomena witnessed. I will describe the processes as they are usually seen to occur in the web of a frog's foot. The interdigital membrane being spread out upon a plate of glass and viewed with a power of 300 diameters, * Bat's wings can be well used, and, within a few years, the phenomena in question have been quite satisfactorily studied in this way, with the advantage that the bat is a warm-blooded, mammaUan animal. f Kaltenbrunner ; Experimenta circa statum Sanguinis et vasorum in Inflamma- tione, Monaohii, 1826. (A rare work, which I have not seen in this country.) ITS PHYSIOLOGY AND PATHOLOGY. 775 you perceive the capillary bloodvessels existing as channels in the tissue, and the blood and lymph corpuscles rushing along in them with a kind of pulsatory movement. This is the healthy circulation. But, if the membrane be irritated, the appearances quickly change. In the first place, the vessels become narrower, and there is a consequent increase in the blood's current. This destroys the natural pulsatory movement, and gives a crowded aspect to the corpuscles in the ves- sels. But this condition of contraction is soon followed by the oppo- site (constituting the second stage), relaxation, in which the vessels apv>-N"r Urgef ;^jn fact, their diameter is increased one-third to one- ioaith. Accompanying this relaxation, is a stagnation of the blood's current, and the dilated vessels, crammed with red corpuscles, pre- sent a very red aspect. With this cessation of the current, cease the primary phenomena. This constitutes congestion, and after congestion comes effusion. But we are led to inquire the cause of this stagnation. We have first, contraction, and then, relaxation of the vessels, and this stoppage occurs with the latter condition. Now, in my opinion, it is due mainly to a change in the natural rhythm of the vessels or their walls, and when this has once occurred, the relation of the blood to the vessels is quite altered — at least, mechanically — and a "clogging up" ensues. This alteration ex- tending over a small surface, a much larger area is included from the direct connection, so that the clogging up of a single vessel may lead to the same with four or five others connected with it. It will be seen that in this account I place no stress upon the behaviour of the white corpuscles. Mr. Addison* and Dr. Williams,t both of whom, and especially the former, appear to have studied the subject considerably, take a different view of the subject. Accord- ing to them, the first changes consist in the sudden appearance of a great number of the white corpuscles, which begin to adhere to the sides of the vessel ; and, by a repetition of these adhesions all along, the caliber of the vessel is obstructed, and hence stagnation. If we may credit their statements, there seems to be an actual in- crease in the generation of these white corpuscles — which appear to have the power of rapidly multiplying themselves— for they suddenly appear, and that, too, from an unknown quarter. So that the primary phenomenon of the inflammatory process is, according to these observers, a change of relation between the bloodvessels and the white corpuscles. * Addison; Lond. Med. Gaz. Deo. 1840, and Jan. and March, 1841. t Williams; Lond. Med. Gaz. July, 1841. 776 THE cell: But this view appears to me incorrect, and its fallacy will be apparent to any one who carefully considers its phenomena. In the first place, from what we have already learned of the nature and relations of the white corpuscles, it is, to say the least, quite unphy- siological to suppose that there is a sudden increase in their genera- tion at the time of the irritation. I have always regarded this as the outstanding objection to this view. Moreover, the experiments were made upon frogs, and the irritation produced by acetic acid ; and I cannot but believe that they were deceived by the nuclei of young blood-corpuscles, which were caused to escape, and rendered distinct by the acid, and which quite closely resemble, as we well know, the colourless or white corpuscles. In fact, the action of the acid is so sudden that, in many cases, the replacement of red by apparent white corpuscles, is, as it were, by magic. Then again, there is another source of error. It is well known to all who have experimented much with frogs under the microscope, that the rela- tive quantity of the constituents of their blood varies very much. Thus, in young and full-fed frogs the number of white corpuscles is very great, even exceeding that of the red; whereas, in old and more famished ones, the opposite is true. Now, it is apparent, that if the experiment is made with the first, one would be quite likely to be deceived by their unusually great number. While, if frogs be taken in the spring of the year, when half famished, a quite different aspect is presented. Mr. Addison thinks he finds support for his opinion in the fact that blood drawn from a pimple, the base of a boil, the skin of scar- latina, &c., in the human subject, presents an unusual number of the white corpuscles. This fact may have been correctly observed, but all my inquiries in this direction lead me to believe, that if, in such cases, there is a disproportion between the white and red corpuscles as to numbers, it is not local, but exists throughout the entire quan- tity of blood. In proof of this I may mention the fact, which I have often verified, that if the finger of almost any cachectic, tuber- culous patient be pricked, the blood therefrom will be found to abound in white corpuscles. Moreover, such persons are those most generally afi"ected with cutaneous eruptions, boils, &c. In making these remarks, I wish to be understood as not urging any objection against the view that, in inflammation, there is an in- crease generally of the number of white corpuscles, or rather that there is a deficiency of the formation of the red ones out of them. ITS PHYSIOLOGY AND PATHOLOGY. 777 For this view I believe correct in the main, but it appears to be rather referable to general and constitutional conditions. I am therefore inclined to the opinion of Dr. Bennett and Wharton Jones, that an especial abundance of the white corpuscles in an in- flamed part is neither a frequent nor constant occurrence. And this, I may add, is borne out by the experiments of Remak, who observed that those portions of blood first drawn in inflammation contained but few white corpuscles. What, then, are the primary phenomena of inflammation as ob- servable by the microscope ? As we have just seen, they may be regarded as the following: 1. Contraction of the vessels, with a consequent acceleration of the current. 2. Dilatation of the vessels. 3. Stasis, or cessation of the current. This constitutes that con- dition of congestion which necessarily precedes the inflammatory process. But the confusion must be avoided of supposing that these phenomena constitute inflammation ; for this is not really so ; and we may have them all, as in cases of ordinary congestion, without any inflammation following. But at the same time, I should remark that we ought to be careful about the use of this word congestion; for it would appear that the congestion preceding inflammation is quite different from that which is a simple hypersemia of the vessels. They may pass into each other, but the general experience is that there is no necessary connection. But in the initiatory phenomena of inflam- mation, what is the cause of the stasis ? I have already expressed the view that it might be due to a disturbance of the natural rhythm of their action. But this, I am free to confess, does not explain the whole matter. We know very well that the outstanding causes of inflammation are of two kinds — traumatic or external, and idiopathic or internal ; and, as far as we understand the subject, the sequent phe- nomena are the same in each and both. If we say that inflammation is due to an altered relation between the bloodvessels and their con- tents, I do not think we are any nearer the ultimate cause ; for this is only expressive of a condition. In inflammations of a traumatic origin, we regard the disturbance as commencing with the parietes of the vessels ; but in those which are idiopathic or constitutional, we trace the first trouble to the blood, which subsequently acts upon the vessels. But there is, I believe, a third form, not originally due to either, and which has been well de- scribed by Mr. Paget.* It may, in one sense, be called of nervous * Paget; Lectures on Inflammation, &o. in Banking's Abstract, No. 12; or Lectures on Surgical Pathology, &c. 2 toIs. London, 1853. Vol. i. p. 292, et seq. VOL. VI.— 50 778 THE cell: origin, and I can see no reason -why the nerves should not so control the vitality of the vessels as to lead to these phenomena. Notahle instances of this form are, inflammation of the conjunctiva after se- vere use of the retina ; the excited state of the optic nerve being communicated to the filaments of the nerves of the conjunctiva, causing them to alter the nutrition of the part ; also, inflammation of the testicle from severe irritation of the urethra, which is only to be explained by a disturbance of the nervous power controlling the nu- trition of the testicle. There are also many phenomena connected with neuralgia coming properly in the same category. As yet, therefore, we cannot look for the cause of inflammation in any one circumstance alone ; or, in other words, we as yet know nothing of the intimate nature of those causes producing the initiatory pheno- mena observable by the microscope. Undoubtedly the chief of these last is the stagnation, and, in my opinion, when we have discovered its relations, we shall then have learned quite definitely about the whole matter. In conclusion, I will say that, if we are to remain on the ground of demonstrable facts, it cannot be said that the microscope has been of eminent service in elucidating the real nature of the inflammatory process. In fact, that it should be, would be expecting too much. With means of physical examination, we can only seize hold of phy- sical appearances. The forces of matter and that which concerns vitality, cannot, at present, be studied by these aids. And it is my opinion that the intimate conditions of this pathological state are not only beyond microscopy, but beyond chemistry. The microscope, in revealing to us the outstanding phenomena, such as I have described, has accomplished all that could be justly expected ; and although this is not much, it has served at least as a physical basis of our knowledge of the subject. The secondary phenomena of inflammation commence immediately succeeding upon the stasis. They consist of two kinds; first, the effusion of the plasma as a hyaline liquid into the contiguous parts ; and second, the formation of utricular and cell products in this plasma. These formations constitute the heteromorphous products, which, in pursuance of the remarks I have hitherto made, I have seen fit to consider as at least the sequelae of the inflammatory process. In the following chapter, I shall take them up in special detail. ITS PHYSIOLOGY AND PATHOLOGY. 779 CHAPTER IV. HETEROMORPHOUS PATHOLOGICAL PRODUCTS. I. Utricles or Granules. We have already traced, in a rapid way, the features of abnormal nutrition, as a condition ; we will now take up the description of its material expressions. Thefluid hyaline blastema, we have already seen, is the first pro- duct of the diseased action. Rarely, however, does it remain as such, but advances toward a higher state. The chemical nature of this fluid, as proved by analysis, is oleo- albuminous — that is, composed of oil and albumen. But these ele- ments as they first exist are transparent, and some combination is necessary that they may be made visible, appearing as separate particles. This is accomplished in physiology exactly as in pathology, and I have already given its description. The utricles thus formed are also in appearance exactly like those of health, and like them, too, they are the basis of all the higher cell-forms. These forms may be the pus, the tubercle, or the cancer cell. , The most simple heteromorphous product is of course a plasma or blastema perfectly hyaline, which has not sufficient vital capacity to give rise to even these low products. Such are, for instance, many serous efi'usions, transudations of the larger bloodvessels, which analysis shows to be mostly composed of water. Notable instances of this are the effusion of a healthy blister, and the effusion into the plasma consequent upon the more laudable forms of inflam- mation of that organ. As such, they may be entirely absorbed exactly as they were thrown out. A little more active form of this liquid is that in which these utricles appear, but which have not capacity enough to pass on to cells. Such are many effusions, from the so-called scrofulous inflam- mations, or those occurring in individuals whose natural standard of vitality is below that of true health. These are never wholly absorbed, but leave their marks behind them in the form of adhesions, lymph, &c. &c. These last have the lowest form of organization — the fibril- lated structure, and the details of which are exactly like those of health already described. Utricles and utricular formations constitute a large portion of pa- 780 THE cell: thological products, and a large portioft of these products are directly referable to the inflammatory process. I have already said that a utricle is only a cell in embryo ; but in these low plasmas the ulterior state of a cell is the fate of comparatively few utricles. In fact, this remark is true, literally, of all pathological plasmas ; and this is the reason of the wide disproportion in numbers and amount of utricles and cells in pathological formations. Most utricles do not get be- yond their primitive condition. This is a state of things quite for- tunate ; for, were every pathological utricle capable of cell-develop- ment, there is reason to believe that our physiological condition would oftentimes be obliged to recede before engrossing pathological growths. In utricles, then, we have the commencement of solid abnormal products, and these utricles have always the same aspect ; they may have a lower or a higher destiny, according to the vital impulse of their blastema. We will now look to their ulterior forms. II. Cells and Cell-fokms. The cell is the highest condition attainable by a heteromorphous pathological product ; it is the ultimate and not the transitional form. These cells, born with no preconceived end or aim, and arising in a blastema which has no physiological impress, have lives ending in abortion. They fulfil no function, except in some instances that of a feeble and imperfect reproduction ; they soon pass away, or if they grow (not developed), they show their want of any affiliation with the economy, by their being recognized by it only as foreign bodies. Most of them are as imperfect in their physical conformation as they are in their physiological destiny. On this account, they can, with the exception of some of the higher forms of cancer, be recog- nized as morbid by their anatomy alone. In our physiological studies, we have been led to place a high importance upon the nucleus of the cell, for it not only indicated the adult and potent condition of the cell, but had otherwise a vital value. In pathological cells, it may and often does exist ; but if so, it is generally imperfect, and is so little expressive of the power of the cell, that it does not rise to the dignity of unity, but exists in several parts, constituting the so- called nuclei of cells. 1. The Tubercle-Cell. — This I regard as a very good example of the lowest cells or cell-forms existing in either healthy or diseased tissues. It constitutes the expression of a very slight elevation of an organ- ITS PHYSIOLOGY AND PATHOLOGY. 781 ized form above that of a utricle. The plasma in which it is formed is filled with utricles, which have no distinguishing features from those of others. Sotne (but few) of these utricles increase and form a cell-membrane, containing a clear liquid, in which last, granules appear, but which remain as such, never forming a true nucleus. Thus it is, that, as far as my observation goes, tubercle-cells never have a nucleus proper, but only several granules. These cells thus formed vary in size from jj^ to —^ of an inch in diameter. As I have sometimes observed them, quite soon after formation in the tissue of the lung, they were even larger than this — about j^ of an inch in diameter. But they are rarely seen under these circum- stances ; and as usually observed, taken from tuberculous matter of various organs, they are much smaller, and present a much less regu- lar contour and appearance. They then have a somewhat shrivelled aspect, are rather angular, and the granules are more distinct. This is due, I think, to a partial exosmosis of their contained liquid. Upon being treated with acetic acid, the membrane becomes quite transparent, thus rendering the contents more distinct. The distin- guishing characteristics of the tubercle-cell belong, therefore, to its low condition. Moreover, it is an adventitious product, and always exists as non-nucleated, having a finely granular aspect. These pe- culiarities are sufficiently well marked to make it always distinguish- able by the microscope, and especially so, if combined with that first- sight knowledge which long-continued observation always gives. So that one may be able, the moment he sees the cell, to pronounce whether or not it is tubercular. Then, again, these cells have a uniformity of appearance quite remarkable, so that, once fully recog- nized, one would know them pretty certainly afterwards, wherever formed. Fig. 37. y<^ c m w. B^^ $l^M^-Mf$- ^fi^^lf;^M >^i'i 4^;';:^^' Tntercle-oellB in varioua stages, from lung of patient dying of acute phthisis. ». Freshly deposited cells lying in the structure of the lung. b. Old tubercle-cells from tuberculous masaefl, the usual appear- ance of the cells as found in the yellow masses, t. Usual appearance of tuberculous matter under the microscope — cells in the midst of granules. (Magnified 350 cUameterfl.) 782 THE cell: I do not, of course, regard this uniformity of appearance as any indication of their possessing a distinct type ; because, as I have be- fore remarked, morphological types do not belong to pathological structures. Moreover, the tubercle- cell, wherever formed, or in whatever organ, or in whatever animal — horse, dog, &c., is the same. This uniformity, therefore, must be considered as quite referable to the plasma in which they are formed. But this tubercle-cell, although always present in tuberculous pro- ducts, constitutes only a small part of their substance ; for, from the very fact that it is one of the lowest products, utricles compose by far the greater part of tubercle as a product. And fortunate it is that these granules are nearly all of them thus feebly endowed ; for, were they all capable of cell attainment, man would stand no chance against the ravages of a disease which even now, as it is, decimates his numbers. These utricles are, of course, composed of oil and albumen, but in many instances, and especially when the blood is rich in oily matters, the oil predominates over the albumen, and you then have oily parti- cles scattered through the mass. It is not uncommon, therefore, to see in the field of the microscope great numbers of oil-globules in a free state, beside the utricles and cells. Fat-globules, utricles, and cells are, then, the visible microscopic parts of the tuberculous pro- duct ; and, from a quite extended series of examinations I have made upon tubercle, not only as occurring in nearly every organ of the human body, but also as appearing in some of the lower animals, I am satis- fied that these are the only parts properly belonging to it. It never attains a farther organization ; on the other hand, fortunately, all its tendencies are of a retrograding character. Pathologists, guided by external appearances, have divided tuberculous products into two kinds, the gray and the yellow forms; the former occurring in a dis- seminated manner, the latter in large masses. But this distinction has no foundation in a difiierence of the cell, but is due to there being a greater amount of fatty and utricular matter in the yellow than in the gray variety ; which last is composed mostly of cells. In thus giving the tubercle-cell and its accompanying plasmatic forms a distinctness of existence — a kind of individuality, it may be asked if I regard it as a true inflammatory product. To this I reply in the affirmative, meaning thereby that the effusion of the tuberculous plasma is the result of an abnormal condition of the blood generally, which condition, in the present state of science, must be considered ITS PHYSIOLOGY AND PATHOLOGY. 783 as belonging to inflammation, as we have been led to understand the meaning and intimate signification of this last. This abnormal condition of the blood has been called the tubercu- lous dyscrasia ; which, judging from its products, has an undeviating uniformity. This leads me to express the opinion which I have long entertained, that the appearance in the system of the tubercle-cell is always due to a general rather than to a local pathological condition. I know it is true that its expressions are sometimes simply local, but this is rare, to the misfortune of our race. The peculiarities of its deposition in the different organs and tis- sues of the body do not properly belong to this work, and however important and worthy of consideration in a practical and therapeuti- cal point of view, they do not relate to their histology, for this last is always the same. When the tuberculous product has reached the cell-form, it has attained its highest point of organization. Then, like all morbid products which are produced under physical and not with teleological relations, it dies, and undergoes all those peculiar changes of which an organized product is capable while existing in a living tissue. It retrogrades to its primitive elementary condition, then a chemical dissolution takes place, the aqueous portions are absorbed, a thick wall of cicatrical tissue is formed around the residue, and thus the radical cure of tubercle is sometimes effected. Such, my own experience teaches me, not unfrequently occurs in the pulmonary tissue, and in the lymphatic glands. The course of tubercle, then, is such as we should well expect it would pursue. But in thus regarding the tubercle-cell as strictly an inflammatory product, it is asked, how are to be reconciled many of those pheno- mena of its appearance in organs, and especially in the pulmonary tissue, indicating at first a dissimilarity to the usual inflammatory conditions ? I can well appreciate the force of this objection, for I once re- garded it as suflSciently valid to make the distinction broad between these two processes. Louis and other pathologists have shown that it is true that inci- pient pulmonary tuberculosis generally commences at the apices of the lungs, while pneumonia or ordinary inflammation nearly always commences at the base. Then, again, both the clinical course and the gross pathological anatomy of these two affections are quite distinct, and seem never to completely fuse into each other. But these distinctions are not more 784 THE cell: wide than the intimate causes of these two affections, as far as we understand them. As I have before remarked, the causes of tubercle are as deep and general as the very constitution of the individual ; they are constitutional, and this is the reason why they may be here- ditary. On the other hand, the causes of simple inflammation of the lungs are of a more local and particular nature, and due, generally, to direct influences of external agents. These should be sufficient rea- sons, I think, why their outward manifestations are somewhat dis- similar. From the very fact that the inflammation of tuberculosis is consti- tutional in its origin, we might well infer its very low character. This, the soundest practical experience has shown to be true ; for although even its very earliest expressions are attended with a gene- ral febrile condition, yet this last is always most successfully managed by a sthenic rather than an asthenic mode of treatment ; and this, I may add, is one of the happiest and most important results of modern pathology ; and although its first recognition was due to clinical studies, yet we have learned fully to appreciate it from the results of microscopical analysis. 2. The Pus-Cell and Pyoid Forms. — We now come upon those products which are, without dispute, directly referable to the inflam- matory process. As far as the most careful experience has yet shown, they are never found without there has been a pre-existing inflammation ; neither does there ever occur inflammation without their formation to a greater or less extent. Under the above head, I in- clude not only the true pus-corpuscle, but all those cell-like, granular forms with which it is usually associated to a greater or less extent. An inflammation exists, an abnormal plasma of the blood is thrown out, and in this, the first traces of an organizing force are manifested, as usual, by the appearance of utricles. But these have no distin- guishing characteristics, looking exactly like those of tubercle or cancer. Soon, however, cells are formed from them in the usual way, and, in what is called "laudable" or creamy pus, they compose the greater part of the solid portion of the pus-liquid. Compara- tively few granules or utricles remain as such, and thus is manifested its formative power over and above that of tubercle just described. The cells thus formed consist of a membrane filled with liquid, in which are three or four granular bodies, which, aggregated together, constitute its nucleus. It is, therefore, a granular nucleated cell, having a diameter varying between -j^ to ^ of an inch, but the average of which, according to my own experience, is about -^ of ITS PHYSIOLOGY AND PATHOLOGY. 785 an inch. I am not aware that its size or aspect varies to any extent, from whatever part it may be taken. The same is true with refer- ence to the other mammalia I have examined — such are, notably, the horse and dog. The true pus-cell, therefore, presents a very great uniformity of appearance, perhaps full as much as that of tubercle. When treated by acetic acid, the cell-wall becomes quite transparent, the nuclei are most distinctly seen, and, if the action of the acid be sufficiently direct, the wall is quite dissolved, and their escape takes place ; pure water enlarges them by endosmosis, so that they appear full and plump. There can be no doubt, therefore, as to the existence of the cell-membrane. Fig. 38. twrt^i Pus from an abscess, a. Pus-corpuecles, granular and nuclei, indistinctly seen. 6. The same treated with acetic acid, revealing a dear membrane, inclosing three, four, or more nuclear granules. However, in these days, a detailed description of the appearance of the pus-corpuscle under the microscope, seems quite unnecessary, for every person can see for himself, and that, too, which no words can as well describe. Although the pus-corpuscle, thus formed, as the product of what is called a true " healthy" inflammation, can always be definitely described, yet all inflammations are not equally active, and their products are very far from being as well formed. The pus-cell being the highest of its cell-products, the others with which we meet are of a lower character — they are cell-forms, but retain a good deal of their utricular character. Such are the pyoid corpuscles described by Lebert,* and such also are the inflammatory corpuscles of Gluge,t and many other illy-formed and badly-defined bodies which have no proper name, but which are met with in indolent suppurations, and especially in the expectoration.J * Lebert; Physiologie Pathologique, Paris, 1845, torn, i, p. 46. t'Gluge; Anatomisch. Mikrosc. Untersuch. zur Pathol. Minden, 1838, p. 12. t Gruby has described very many forms of puB-corpusoles occurring in different parts of the body. He thinks the peculiarities are constant, and therefore puts much stress upon them, a view not at all supported by more recent labours. See Gruby's work in Latin — Observationes microscopicae ad Morphologiam Pathologioum, &c. Vin- dobonsB (apud Singer et Goering) ; a partial translation of this may be found in the Microscopical Journal, 1840-1842. 786 THE cell: The fyoid corpuscles, although often having ■well-marked characters, scarcely deserve a separate name ; for the products of inflammation Fig. 39. Ikfi %%.. m ■'M^ $m ^1 Pyoid corpuscles from meningitis, showing that they differ from those of pus in being larger and more delicate. (Magnified 350 diameters.) being all abnormal, we cannot well expect any adherence to a defi- nite type, but a variation or oscillation to a considerable extent. They occur as the products of inflammations of cachetic individuals, mixed with a few true pus-cells. As I have seen them, they are one-third larger than the latter, and contain, within their interior, many small granules instead of nuclei, and, on the whole, seem more delicate; and, if I may thus express myself, are more rudely put to- gether. They are, therefore, easily distinguished from the " normal" pus-cell. Both from their aspect, and the individuals in whom they occur, I should say that they constitute the transitionary form between the tubercle and pus-corpuscle, if the present state of our knowledge of these products would allow us to admit that there ever occurs any transition from one to the other. And then, again, it may be asked if such phenomena would not lead us to believe in this very transi- tion T For my own part, I cannot say that they would or would not; but, at any rate, they have constituted one ingredient of my opinion that tubercle was really an inflammatory product. Fig. 40. Inflammatory corpuscles, being only enlarged sacs filled with granular utricular matter. (Magnified 350 diameters.) The inflammatory or granulation corpuscles of Gluge were pointed out by him long ago. He regarded them as products of inflamma- tion, but was decidedly in error in attempting to explain their appear- ITS PHYSIOLOGY AND PATHOLOST. 787 ance or presence as the nuclei of blood-cells. Their distinguishing features from those of the pus-corpuscle are much more marked than from those of the pyoid corpuscle -we have just considered. And yet, these features can scarcely be described ; for the corpuscle, as a ■whole, shows a want of regularity in almost every particular — seem- ing to be the rudest expressed form of organic power — under the semblance of a cell. They are simple sacs, filled with a fluid in which float granules, in numbers from two or three to so numerous as to make the whole a semi-opaque object. As might thus be expected, the variability of their size is very wide — from y^ of an inch to that discernible by the naked eye. However, the size most frequently met with, is that of about ^y^- of an inch in diameter. When in con- tact with chemical agents, they behave like delicate forms; that is, the envelop begins to be dissolved, and therefore is rendered more clear, and finally ruptures, discharging its contents. In this respect, it does not difier from ordinary corpuscles of any kind, the envelops of which have been rapidly formed or are delicate. Their mode of formation might almost be deduced from their physical appearance, for they are only sacs containing granules and fluid. As far as my observa- tion goes, they appear to be formed by the expansion of utricles into larger sacs, and as the cell-process here ends, the whole result is abortive — not only no nucleus being formed, but the cell-like body showing no individuality as to size. Thus, in some forms of cancer, in which a low, indolent inflammation supervenes, they attain a size so as to be easily visible with the naked eye. The same is true of them as found on the inner surfaces of ovarian cysts. But these monstrosities are comparatively rare, and they may be said to have an average size, a term which is not properly applied to cells or cell- like bodies having an individuality of their own. I think it is well determined that they are the results of the inflam- matory process alone, and in an effused blastema of a very low order; and this inflammation is of a simple nature, having no peculiarities, as might be said to be true of that of tubercle. On these accounts, much value is to be attached to their presence ; since, wherever found, the question of inflammation on other premises cannot be raised. They are met with in dropsical fluids, of any source ; as those of hydrocele, cystic disease of the ovary, ascites, &c. ; also in organs having a low chronic inflammatory process, or at least where the inflammation is of a resolvable instead of a suppurative character — such as in the sputa of pneumonia, inflammations of the skin, and in that low form of nephritis known as Bright's disease. 788 THE cell: And I will add, that my own observation has shown that their pre- sence in the urine is nearly always certainly diagnostic of this dis- ease.* They are also found in all pus to a greater or less extent, as this last may be the less or the more "laudable." 3. The Oancer-Cell—The appearance of carcinoma in the system takes place under circumstances more obscure than those of any other morbid product with which we are acquainted. This is due to its high morphological character ; for, although a heteromorphous formation, it stands far above those we have just been considering. It will be seen that I have included it under the head of inflam- matory products. I admit that, in so doing, I am stepping a little beyond the boundaries of demonstrated facts. But the position ap- pears to me tenable. As a heteromorphous product, all my experience has led me to regard it as the result of an abnormal nutrition, and on a preceding page I have expressed my views as to the relations of this abnormal nutrition to the inflammatory process. Then again, its appearance often holds the relation, with inflammation, of cause and effect. Such is true as occurring in or after wounds of a part, or in the female breast, immediately sequent upon its inflammation. But in these instances we must not put too much stress upon the local lesion; for, as cancer, like tubercle, is always dependent upon a constitutional dyscrasia, its local appearance has other than simply local relations. This statement is broad, and expressive of many of the characteristics of the product ; but, certainly, the tenor of its whole history, as we now understand it, is to this effect : its earliest appearance, in a distinct and unmistakable form, is as a few cells, as I have sometimes observed. We cannot trace it any farther back; but all analogy is in our favour for supposing that, like tubercle, these cells are formed in an unhealthy plasma efiused from the blood. Moreover, upon the inner surface of the testicular tubes, where I have observed these cells just appearing, they seem to replace the normal epithelial cells there situated, and to be formed like them. As the first appearance of the disease is imperceptible in the majority of cases, there cannot be traced any coexistent hyperaemia of the part, or any congestion of the bloodvessels leading to an effusion of the morbid plasma; but in all probability, a condition of this kind does exist ; and the fact that a mechanical injury, such as a blow or a compression, will sometimes give rise to the local appearance of this product, supports • See, for some farther details on this point, an article of mine, The Microscope, and Eenal Affections, Amer. Journ. Med. So. u. s. vol. xxii. p. 373. ITS PHYSIOLOGY AND PATHOLOGY. 789 this hypothesis ; for, in those cases, there is an effusion of the blood- plasma from the local congestion ; and we can justly infer that the reason of its appearance, in that particular locality, is because the mechanical injury -was there received. As I have just remarked, the appearance of an adventitious cell or cells, constitutes the first indubitable evidence we have of the can- cerous product. This cell, the first, is also the last expression of this product, it being the terminal and not the transitional form. It is nucleated, and oftentimes has several distinct nuclei ; but as to size, form, and other external characteristics, there are none, it is my pre- sent opinion, which are constant and peculiar, and by which it may always be distinguished from other cell-forms. Formerly, my view was, like that of most other microscopical pathologists then and now, that the cancer- cell as such has physical peculiarities, by which it can always be distinguished from other cells. But, from a careful review, of late, of the subject, based not only upon observations of the cells as physical objects, but upon a consideration of them as con- stituting an expression of pathological action, I am free to confess that I do not consider my former opinion tenable. All or nearly all the microscopical relations of the cancer-cell which have any claim of being peculiar to it alone, may, I think, be stated in the following brief manner : The cancer-cell, when fully ^formed, is simply a nucleated cell ; it may, however, have several nuclei, or none at all ; it often is of an irregular shape, fusiform, caudate, &c., &c. ; and its size is frequently equally variable ; but the evidence of its being not only pathological, but of what is called a can- cerous nature, cannot and does not depend upon any one of these points alone, but rather upon a combination of them all ; and that, too, united with the fact of these cells occurring in tissues, and under circumstances where they cannot be regarded as a healthy product. From this general statement, it is plain that the cancer-cell has no claim of having a type either of structure or general appearance. As a cell, or as cells, it forms the highest heteromorphous product with which we are acquainted, for it is structurally and morphologi- cally quite above both tubercle, and pus, and pyoid forms. Its dif- ferential diagnosis, which I think can now be made out in nearly every case, depends upon these consideratbns, which, when fully examined, will be found to be amply sufiicient. Suppose, for an illustration, that a small portion of a cancerous tissue has been sent to a microscopist for microscopic examination. He de- cides, in the first place, that the tissue in question is not a normal one. 790 THE cell: from the fact that its cell-constituents possess no type peculiarities. As a heteromorphous product, then, the diagnosis lies between its being .mm Examples of caneer-cella, showing some variety of shape and general irregulax character, w. Very regular nucleolated cells, from cancer of the arm. h. Irregular cancer-cells, and such a£ are more com- monly met with. c. Cells very large, and in which daughter-cells have heen formed. (Last two from cancer of the hreast.) I give here a few figures only, hecause a correct idea of the cancer<»ll, as an aher- rant form, can be learned only from direct study by means of the microscope. tubercle, a pyoid form, or cancer ; and, from what has just been said, one can easily see that the decision that it was the last, or cancer, would not be difficult with a person who has long practised upon these products. But I may here remark that its differential diagnosis from certain homologous morbid products, although in my opinion quite clear, cannot always be as distinctly and positively made out. This point, however, belongs to a future page. All homoeomorphous cell-products possess, to a considerable extent, as I shall soon attempt to show, the type-characteristics of the tissue to which they are homologous. All heteromorphous cell-products are character- ized, as I have before said, by an absence of these type-forms. From these data, I think the experienced eye can always, or nearly always, decide correctly upon cancer-cells, when they exist in numbers sufficient to form a distinct product. On the whole, the high degree of organization is that which characterizes the carcino- matous product from that of all others of a heteromorphous nature ; and, according to the scheme laid down on a preceding page, it may be justly inferred that the line between cancerous and non-cancer- ous products is always clearly defined, and also that they never pass insensibly into those of a healthy character. The question may be fairly asked, In what consists the so-called " malignity of cancer-cells ?" Space does not allow me here to criti- cize or even examine the different definitions given by various writers to the term malignant ;* but if we are to understand by it the power * It is quite remarkable to observe the obscurity of this point, not to mention the incompatibility of the notions entertained. Some writers define malignity to ITS PHYSIOLOGY AND PATHOLOGY. 791 of a morbid product to replace a healthy tissue, to reappear, after removal, in the same or in a distant locality, and finally to com- promise the life of the individual — if this, I say, is the definition of malignity, I think a tolerably satisfactory answer can be given to the question. It lies, in the first place, with a heteromorphous pro- duct, and its appearance here or there is but a local expression of a constitutional dyscrasia. So far, the peculiarities of cancer are parallel with those of tubercle. But it differs from tubercle in possessing a much higher organization. The constituents of tubercle are only cell- like forms ; they have not risen to the dignity of nucleated cells. Their life, therefore, is finished with their formation, and the product increases by addition rather than by growth. Not so, however, is it with cancer. Its constituents are nucleated cells, whose existence is not completed by their simple formation ; for they grow and increase, and new cells are formed within them, from their nuclei. They may be said to constitute potential germs, capable of an indefinite growth and reproduction, requiring only a nutritive material in which they may be formed. The so-called malignity of the cancerous product may, then, be said to be due to its constitutional origin, united with a power of in- dividual reproduction by the endogenous and exogenous formation of cells. In fact, it may be said to be due to this last alone ; for, I may add, did tubercle-cells possess the high character and individual power of those of cancer, they would be equally as malignant.* Its capability of self-propagation and perpetuation, after being once formed, by the successive multiplication of cells, gives it a power of almost limit- less expansion. Its liability to a plural appearance is, of course, due to its constitutional origin, for this is equally true of tubercle. But its liability to a reappearance in the same locality after removal, is dependent, probably, upon both the constitutional in- fection and the circumstance of a small portion being almost neces- sarily left behind, which serves as a basis for the building up of be the sum of the properties possessed Iby cancer. Others define the word as that of incurable. Others base a definition of the term upon anatomical appearance, as, for instance. Dr. Hodgkin, who regards growths with a cystiform structure as malignant. But with a majority of writers, the term appears to have a very vague signification. The notion of a malignant disease exists in their minds as an entity, possessing irre- sistible destructive agencies and tendencies, manifested by a reappearance in a worse form as often as apparently entirely removed. * The independent vitality of the cancerous tissue has been well shown by some curious experiments by Dr. Leidy, who introduced portions of it beneath the integu- ments of frogs. See Proceed, of the Acad. Nat. So. Philadelphia, vol. v. p. 212. 792 THE cell: a new product. For, both theory and experience teach us, that a cancerous product being entirely removed from a locality, that lo- cality or tissue is not any more liable to its reappearance than it was previous to the first invasion. We may, therefore, conclude that the malignant character of the cancerous epigenesis, in contra- distinction to that of other morbid products, is, after all, due to its high power of individual ceW-reproduction. This is reducing the whole to morphological peculiarities, which are based upon our best . appreciation of the nature of morbid cell-products. Hitherto, we have considered only the true histological product of cancer — the cell. But the cancerous tissue, from the very fact of its being a pathological one, includes other elements, which may well be mentioned here. In a very few instances, I have met with the can- cerous tissue as consisting entirely of cells ; but this is quite rare, and occurs only when this epigenesis exists in its highest state. Ele- ments of an inferior character generally enter largely into its com- position, and these are such as are found in most other morbid growths. One of the most constant of these is an amorphous granular sub- stance, produced by the condensation of the granular matter. This is often so tough as to resemble a fibrous tissue ; and, in cancers of a slow growth, forms a large ingredient of their substance. It is the framework on which the more delicate parts rest, and, in the higher forms of cancer, the grades of its transition into a fibrillated tissue are imperceptible. The second element, almost equally as constant, is granules of various sizes, scattered everywhere. These are often expanded into cell-sacs, which are crowded with fat-globules. These fat-globules exist in a free state also, and often in such abundance as to give to the whole mass a decidedly fatty character. Crystallized fat, or cholesterin, is often found. And thus it is that fat and albumen, in these imperfect copditions, form a large portion of the non-solid constituents of cancer. In many instances of this disease as occurring in the breast, it was evi- dent to me that its rapid increase was due to a simple efi"usion of these elements, rather than to the increase of cells. In fact, my own experience is that the secondary forms of cancer, or the primary ones, after the cachexia is fully established, are for the most part made up of these low amorphous constituents. In those of larger size and more active character, bloodvessels are ITS PHTSrOLOQY AND PATHOLOSY. 793 found. These hsive, as Berard* has shown, the most simple struc- ture, being tubes whose walls are composed of a single membrane. But the other peculiarities of the bloodvessels insisted upon by Be- rard, I have never been able clearly to make out. It does not belong to me in this place, to dwell at all upon those peculiarities of physical appearance which many authors have thought sufficiently well marked and constant to serve as the basis of a very minute classification ;t for these are points of much less scientific importance than the histological relations we have just considered. In fact, it may be fairly questioned if such divisions are in any sense scientific ; and in support of this, I need' only refer one to the incon- gruity of opinion existing upon this subject. There is, however, this much certain, that the growth and con- dition of a cancerous epigenesis is dictated very much by the activity of the nutrition of the part in which it appears ; and its first appear- ance is undoubtedly the same wherever it may be, that is, consisting of a blastema in which appear cells. Thus, when occurring in highly vascular organs, such as the brain and the eye, its growth is rapid, and consists almost entirely of cells. These forms have been called eneephaloid. But when occurring in tissues less vascular, and in which the nutrition is less active, its growth is much more slow, and the cancerous blastema secondarily effused, less organizable. So that cells are not so numerous, but the growth is, for the most part, made up of a coagulated, fibrinous, granular fluid, constituting a kind of fibrillated or fibrous tissue. These forms have been called scirrhous, and when a pigment forms a constituent of either the eneephaloid or scirrhous forms it is then called melanoid. Such are the distinctions which have been made, and which are convenient for use. But even these, few as they are, pass into each other on every side. Some call certain forms scirrhous which others think scirrho-encephaloid, &c. &c. It is enough for me that I should look at the subject of cancer as an histological product — as the expression of a constitutional dys- crasia, under the form of the highest pathological cell with which we are acquainted. A discussion of the exciting causes of cancer, its development, dis- tribution in this or that organ, its decay and consequence, belongs to *P. H. Berard; Diet, de Medeoine, in vol. xxx. art. Cancer, t For a good illustration of this subdivision of forms, see Walshe's work, The Na- ture and Treatment of Cancer, loudon, 1846, p. 10. VOL. VI. — 51 794 THE cell: its clinical history. It would of itself be sufiScient for a volume, as it already has been in several instances (Walshe and Lebert) ; and, ■"following the plan pursued in the consideration of the other hetero- geneous products, I purposely omit here anything of this kind.* CHAPTER V. HOMffiOMORPHOUS PATHOLOGICAL PRODUCTS. In the pathological portion of this work, our attention has hitherto been occupied with a consideration of those morbid pro- ducts which have no histological affinity with healthy tissues. They were, therefore, properly termed heteromorphous ; and in the scheme of the origin of all morbid products which I advanced on a pre- ceding page, I regarded them as the results of perversion of the plasma, which not being at all acceptable to the tissue into which it is effused, its low organizing power gives rise to products of an infe- rior character, which are at the same time quite dissimilar from any found in the healthy economy. But in discussing pathological con- ditions, one always perceives, on account of the anomalous nature of the subject, that the landmarks and exact definitions of natural science cannot be used. Thus, although I think that heteromorphous pro- ducts are due to a perversion of the plasma or that condition known by the general term inflammation, yet, in some instances, this does not seem to express enough. For in the case of tubercle and cancer, another condition is coexistent (I do not say causative). This con- dition is what is called a constitutional dyscrasia, or an assemblage of depraved conditions leading to local expression of disease. * Owing to the attention which the subject of cancer has excited with all patho- logists from the earliest times, its bibliography is very full. I cannot pretend to give it here; but it will be found carefully and excellently drawn up in Dr. Walshe's work on Cancer (The Nature and Treatment of Cancer, p. 246, London, 1846). Since the work of Dr. Walshe, however, several excellent monographs have appeared, among which the following may well be mentioned here : Lebert; Physiologie Pathologique, Paris, 1845, torn. ii. p. 241. Vogel; Zeitsch. fur Natur. Med. Bd. iii. 1 heft. Bruch; Die Diagnose der boesartigen Geschwulse, Mainz, 1847. Virchow; Archiv fur Pa- thol. Anat. und Physiol. Bd. iii. Bennett ; On Cancer and Cancroid Growths, Edin- burgh, 1849. Lebert; Traits pratique des Maladies Caucereuses et des affections curables confondues aveo le cancer, Paris, 1851. ITS PHYSIOLOGY AND PATHOLOGY. 795 We can get only approximatively at the intimate relations of dis- ease ; this may as well he stated first as last. Both microscopy and organic chemistry have quite failed to teach us anything respect- ing the ultimate data of pathological phenomena. I have thought these remarks somewhat called for, before I pro- ceed any farther, for, in regarding all pathological products as, due either to a perversion of the plasma, or the type-power, I would not wish to be understood as thereby expressing the view that, by such scheme, the nature of all pathological phenomena can be compre- hended. The remaining morbid products which we have to consider belong to another class. In every instance they simulate the physical ap- pearance of the healthy tissues. They are therefore properly called homceomorpJious. As I have stated on a preceding page, I do not regard these pro- ducts as simple hypertrophies of the healthy tissues. For hypertro- phy is simply the increase of the normal form, without the addition of a morbid element. Then, again, homceomorphous products, although they simulate, yet they do not exactly resemble, the healthy structure. They always want their beautiful regularity and uniformity of physical contour, not to mention the entire want of function. I admit that, judging from mere physical aspect, it is often quite difiScult, if not impossible, to draw the line between a true morbid epigenesis and a simple hyper- trophy of the normal tissue. But, in my opinion, the line of de- marcation is always distinct histologically, and in no instance is there a transition of the one into the other. These remarks, although applicable to all homceomorphous morbid tissues, are especially true, as we shall soon see, of the so-called hypertrophies of glands. I regard all homceomorphous morbid products as simple epigeneses, or as always analogous new formations upon the healthy tissues. And when I use the word always, 1 make a statement of more physiologi- cal importance than would at first be supposed, for I thereby deny that new analogous tissues are ever produced, except in conjunction with the normal ones, through the influence of which alone they are developed. In fact, it appears to me that to admit the opposite view, that tissues, like the normal ones, may be formed anywhere adventitiously, is tantamount to the admission of the doctrine of equivocal generation ; because, morphologically speaking, an animal is only a collection of individual tissues, and each of these tissues 796 THE cell: may be said to have in one sense an individuality as distinct as that of the whole animal itsfllf. The pathological relations of this doctrine are of very great im- portance, and I am inclined to look with doubt upon those descrip- tions of the appearance of new tissues in localities quite distant from those in which the same occur normally. Aside from considerations of this kind, doubts might be properly raised from the fact that, in most instances, the evidence that the tissue in question is like the normal one, is based upon gross appear- ances alone. Every-day experience is showing us that, in important cases, we should not, and generally cannot, judge of the nature of a tissue by its mere physical aspects to the naked eye ; and what is more, the liabilities for deception are such that no familiarity can remove them. I shall have occasion on a future page to refer to in- stances of this kind, and also to show that the microscopical struc- ture is, and should be, the only reliable evidence. I may add that, upon a point of this importance, I do not think the ipse dixit of every observer should be taken ; for aside from the comparatively few who well understand microscopy, the number is much fewer of those who know well the characteristic microscopic appearances of tissues. I shall therefore take up homoeomorphous morbid products in the light only of epigeneses. I. Epithelial Epigeneses. From the fact of the wide, indeed almost universal distribution of the epithelial tissue, its pathological epigeneses are more frequent and more important than any other belonging to this class of pro- ducts. There is one other circumstance which may be considered as favour- ing their frequent occurrence. This tissue is composed of simple cells, often existing to be sure under various combined forms ; but its nutri- tion is necessarily delicate, and quite liable to be perverted, or ren- dered abnormal, thus giving rise to these products. As a normal tissue, it necessarily possesses an individual type of structure and appearance; but this has a variety according to the lo- cality. The pathological formations follow somewhat in the routine of this variety, so that, in the same way, there may be said to be diflFerent kinds of epithelial epigeneses. I am not, however, dis- posed to insist upon these refinements. ITS PHYSIOLOGY AND PATHOLOGY. 797 Both for the sake of convenience, and as a somew,hat natural division, epithelial epigeneses may be separated into three groups : — 1. Those occurring upon mucous and serous membranes. 2. Those occurring in or upon the skin. 3. Those occurring in the ovarian tissue. 1. THOSE OCCURRING UPON MUCOUS AND SBROUS MEMBRANES. This group contains by far the largest number of these products; for they are liable to occur anywhere, where these membranes are dis- tributed. But, according to recorded experience, they, are rarely met with except in a few localities. These are, in the uterus,* in the bladder,t in the mouth, antrum, and lip, on the pia mater,J pleura, and peritoneum. But the in- stances which do not belong to the mucous membrane of the mouth are few and isolated. The mucous membrane of the lower lip, where it passes into the epidermic tissue, is a very favourite locality, and the growth formed here is the so-called cancer of the lip. These epithelial tumours have the same structural peculiarities wherever found. They are composed of epithelial cells, or the re- mains of such, combined with low cell-like or vesicular products, all lying in a coagulated, greasy stroma. At the earliest period of their growth, these cells cannot be well distinguished from those of the normal tissue with which they lie in contact ;^but they soon show their pathological character by their want of uniformity of size and shape, and their short lives. Thus, they seem to experience the variety of form and shape which is just compatible with their pre- serving their epithelial-cell type, and, being without function, their membranes burst, after which they are inclosed as flattened scale-like forms, in the cell-liquid and unorganizable plasma -^vhich has coagu- lated. This unorganizable plasma contains fat both combined and free ; and crystallized fat or cholesterih is often found. Very rarely do they contain much or even any fibrous tissue. The whole consists of an abortive cell-product, and therefore without- object and without limitation. The physical peculiarities of these tumours due to their particular locality need not be mentioned here ; they belong rather to the practical than to the histological study of the subject. But * Lebert; Ptysiologie Pathol. &o. torn. ii. p. 16. t For those of tliis kind I refer to the cases of trichiasis, recently so thoroughly studied by M. Bayer. Vide Memoirs de la Soc. de Biologle, k Paris, 1850, p. 167. 1 Lebert; he. ciiat. torn. ii. p. 67. , 798 THE cell: that occurring on the lip, or the so-called labial cancer, needs, how- ever, from its frequency and notoriety, to be separately spoken of. Until within a few years past, it has been regarded as a true cancer- ous product; and even now it is regarded by some pathological microscopists as the transitionary form of the non-malignant into the malignant tissue. Fig. 43. Example of the cell-constituents of epithelial epigeneses. From "cancer'* of lip. a. Ahnormal and irregular epithelial cells, b. Normal epithelial cells from point where epigenesis arose, c. Cells and fibrillatcd tissue, the latter forming~the framework of the epigenesis. d. Fibrillated tissue isolated. But the most careful and thorough histological studies of this tumour do not indicate that it is malignant under any circumstances. In fact,, such is my own view, based upon an experience not very limited, and that, too, with this question in view. Moreover, its whole history and economy is of the same import, and, as far as my own observation goes, there is no proof that it is even connected with a constitutional dyscrasia ; and I will add that its liability to return always depends upon local instead of general causes. A question of considerable both histological and practical import- ance has arisen of late. It is whether, by the aid of the microscope, these simple epithelial tumours can always be discriminated from cancerous products occurring in the same locality. In giving an affirmative answer to this question, I know that I am expressing more than many pathological microscopists would be will- ing to allow. But falling back upon my own experience, which I may be allowed to say has not been inconsiderable, this is the opinion which I maintain, and, were it not out of place, I might cite here several prominent instances, illustrating quite well the basis of this view. If it were asked in what consisted the distinction, I should reply, in the absence of all individual cell-type in the one (cancer); and the presence of it in the other (epithelial epigenesis) ; and the appreciation of these differences in every, or almost every, ITS PHYSIOLOGY AND PATHOLOGY. 799 instance, is sometliing not to be described or figured, but to be learned only by long-continued study of morbid products. Meckel* laid down the law that morbid tissues take upon them- selves the morphological characteristics of the normal tissues with which they lie in contact. It might be argued that, this law being true, cancer occurring in an epithelial tissue would be so epitheloid as not to be distinguished from a simple epithelial product. But it is my opinion that this law of Meckel holds true only of homoeomorphous products. In fact, like the "law pf analogous forma- tion," of Vogel,t it seems expressive only of the same condition of nutrition that, on a preceding page, I have intended to convey in the terms perversion of the type-power. Bdt it does not extend to that other condition, perversion of the plasma, which is the source of he- teromorphous products. But as we are not yet thoroughly acquainted with all the phenomenal conditions of either physiological or patho- logical products, this is a point upon which, from due respect to science, a positive opinion might well be deferred. At all events, the course of study I have pursued has led me involuntarily to believe that the line of demarcation of these various products is much more clear and distinct than would be admitted by other observers. J 2. THOSE OCCUEKING UPON THE SKIN. These constitute the so-called epidemic tumours, which include not only formations upon the skin, such as nails, horn, hair, and external tumours ; but also formations in the skin, or beneath its surface, such as encysted growths, the former being only an eversion, while the latter is an inversion of the skin. The contents of these external tumours • Meckel ; Manuel d'Anat. gen. descrip. et Pp,tli. &a. trad, de Tallemand, Paris, 1825, torn. ii. pt. ii. p. 213. t Vogel; TraiU d'Anat. Path, gen., French ed. Paris, 1847; or, transl. hy Dr. Day, Amer. ed. p. 114. X The bibliography of epithelial' epigeneses is confined almost entirely to that of the so-called labial cancer. The following is a reference to some of the cases, and writers who have devoted particular attention to the subject: — Warren; Surgical Observations on Tumours, &o. Boston, 1839, p. 342. Valentin ; Repertorium, 2 ter Abth. p. 31 1, 1838. Gluge ; Anat. Mikros. Untersuoh. II. Heft, p. 136,, 1838. Velpeau ; Leo. Oral, de Clin. Chirurg. Paris, 1841, torn. iii. p. 138. Walsh; loc. cit. p. 255. Lebert; Physiol. Path. &c. Paris, 1845, torn. ii. p. 376; alo. Traits prat, des Mai. Cancer, &'o. Paris, 1851, p. 611.' Bennett; On Cancer and Cancroid Growths, Edinburgh, 1849. I have observed, microscopically, upwards of 25 of these epigeneses. 800 THE cell: (such as condylomata, &c.)need not here be detailed, for, both generally and microscopically, they are the same as of the epithelial ones just de- Fig. 44. Example of the cell-structure of epidermie epigeneses. When wpm the skin, or eversions, their strno- ture IB exactly lite that of epilholial tu mours. The above are appearances of the inversions, or tumours, heneath the surface, a. Layer of pavement epithelial cells ^ning the sad. 6. Isolated cells, e, Preefat, in globules, d. Citolesterin. All from an encysted tumour of the breast. scribed. In the instances of horn, hair, &c., these last follow so closely in the line of the normal tissue, that, were it not for their irregular occurrence, they could not well be discriminated therefrom ; but their want of the normal tissue individuality is very apparent. In regard to cystic or follicular growths in the skin, they are, as I have just remarked, simple inversions, and are cavities (the external opening or origin of which mayT)e closed up partially or completely) of greater or less size, lined with an epithelial membrane, and filled with epithelial products, mixed up with those forming in a very low plasma, or secreted by the contiguous glands. Such products consist of coagulated albumen, free and combined fat, cholesterin, and ceru- menous matter. They often attain a large size by simple displace- ment, and good examples of them in their smallest form are not unfrequently seen on the end, or about the base, of the nose.* * The literature of the epidemic tumours is very scjittered, and owing to the singu- lar classifications of morbid growths of some authors, they are not easily referred to. They are generally included under the head of encysted tumours, when they are sitUr ated beneath the skin. But when they are eversions, or above the skin, they have been known and described by a variety of names. But for more especial descriptions; based upon microscopical evidence, see — Gluge ; loc. cit. part iv. Vogel ; loc. cit. Amer. ed. p. 220. Lebert ; Phya. Pathol, torn. ii. chap. i. Walshe ; loc. cit. p. 544, et seg. Bennett; On Cancer and Cancroid Growths, Edinburgh, 1849, passim. In the follicles of the nose there lives a parasitic animal (aconw foUiculorum), first described by G. Simon (Miiller's Archiv, 1842, p. 212). It has since been thoroughly studied by E. Wilson (Iiond. Philos. Mag. June 1844, and Phil. Trans. 1845). 1 have seldom found it, and think it quite rare. It belongs to this locality, just as the Fedi- culus capitis does to the head. ITS PHYSIOLOGY AND PATHOLOGY. 801 3. THOSE OCCURKING IN THE OVARIAN TISSUE. Under this head I include all cases of the so-called Cystic Disease of the Ovary. In other words, I regard this form of ovarian dis- ease as simply an epithelial epigenesis developed in the ovarian stroma, and, more specially, this upon the Graafian vesicles. This view may appear singular, hut I base it upon a pretty ex- tended investigation of the subject, recently made. I cannot here enter into the full details of this consideration. But the leading features of this doctrine maybe briefly and concisely stated, as follows : On a preceding page, I remarked that, morphologically speaking, the ovum was only an epithelial cell,' and an ovary may be considered as being only a local (and the only one in the body) collection of epithe- lial cells, destined for a definite object. But, until fecundated, these epithelial cells are subject to those morphological laws which appertain to all cells. The human ovary, then, is simply an epithelial tissue, and, therefore, we ought not to be surprised to find it subject to those morbid conditions which are constantly occurring in this same tissue elsewhere. Its whole structure consisting solely of epithelial cells lying in a fibrous stroma, the number of theSe morbid, conditions must be quite few. In fact, they are almost necessarily limited to an epi- genesis of the cells of the stroma. Experience shows that in almost every case this belongs to the cell-structure, and therefore an epithelial epigenesis may be truly said to embrace almost the whole list of ova- rian diseases. If we carefully refer to the subject, it will be seen tbat the human ovary is a tissue in which we might well expect disease would occur. Until the age of piuberty it is passive, and exercises no ' function. But after this epoch it is the seat of a periodical disturbance. Each month there occurs in it a temporary congestion, leading to the evolu- tion of a peculiar product, the ovum.* Its nutrition as a tissue, therefoi-e, is constantly disturbed, and with individuals whose general condition is not what is, termed " healthy," this disturbance may lead to a permanent change, which, once established, is constantly fostered by each ensuing monthly pe- riod. This disturbance, known by the name of ovaritis, constitutes, in one sense, nearly the sum total of ovarian disease. This, moderi^ * I adopt unhesitatingly the view of Bischoff, that an ovum is discharged each month, in the human female. 802 THE cell: experience of some value and extent has quite clearly demonstrated, and upon data of a gross character alone.* From this abnormal nutrition, an epigenesis arises, and the Graafian vesicles, instead of pursuing that line of normal development which would lead to the evolution of ova, deviate therefrom, and monstrous enlargements and growths ensue. As closed sacs, they are filled with liquid, and, this increasing, they rapidly dilate, and, having attained a certain size, are lined by an epithelial membrane, which arises according to the law of analogous formations. This last is truly indicative of the epithelial origin of the cysts, and we could have no better evidence of their histological nature. The gross appearance of an ovary filled with cystic disease is well known — a collection of sacs of all sizes, which may or may not communicate with each other ; in fact, it is only and especially in those cases where the abnormal development has been general and pretty uniform, an enlarged con- dition of the normal structure of the ovary ; for a thin slice of a healthy ovary has, under the microscope, very much the aspect of or- dinary cystic disease ; and I have often thought that, could the same be magnified with a solar microscope, we should have an appearance quite like that of the advanced cases of this disease. As it is of an epithelial epigenesis, every structure aippertaining to it has an epithe- lial character ; especially is this true of the pavement epithelial layer lining the sacs. In the liquid of these sacs may be found floating epithelial cells, single or in clusters. But in an epigenesis of this size and character, the abnormal nutrition is manifested otherwise than by its simple growth. Active inflammatory conditions are always met with, and these give rise to the various products here observed. Such are collections of pus and pyoid forms, effused blood, albuminous matter, fat, free and confined, and eholesterin. These, together with the serum, constitute the products and contents of the cysts. The uniformity of these results in an histological point of view, can scarcely be appreciated except by those who have studied these morbid products microscopically. And, notwithstanding the variety of forms under which ovarian disease appears and has been described as based upon gross appearances, yet, microscopically, they are ( judg- • On the Pathology of Phrenic Forms of Ovarian Disease : by E. J. Tilt, London, Lancet, 1849, vol. ii. Also, by the same ; On Diseases of Menstruation and Ovarian Inflammation, Lon- don, 1850. Dr. Tilt has collected 248 cases of this disease, traceable directly or indirectly to menstrual irregularities, or uterine disturbances. ITS PHYSIOLOGY AND PATHOLOGY. 803 ing from my own experience), all resolvable to these epithelial ele- ments, and others due to inflammation. Take an ordinary case : We find that the larger cysts have thickened walls composed of a fibril- lated granular tissue, the result of inflammation. New vessels have formed on or in its substance, and its inner surface is lined with an epithelial layer, except perhaps in the most severe cases, where various inflammatory products of - albuminous, fibrous, and granular forms take its place. The liquid contents of the sac are of a corre- sponding nature ; for when the sac has a true epithelial lining, the liquid is mostly serous and clear, although there are, floating in it, flakes of epithelium peeled ofi" from the inner surface. But when the cyst is large and its inner surface is covered with inflammatory products, in place of the epithelial membrane, the contained liquid is more dark, and its contents more heteromorphous in character ; such are pus and inflammatory corpuscles, the latter of which are crowded with dark granules, and often attain a size so as to be distinctly seen by the unaided eye. Fig. 45. By Examples of microscopical forms met with in ovarian cysts, a. Pavement epitlielini cells, form- ing the lining membrane of all th^ cysts. 6. The pus, pyoid, inflammatory, and irregular epithelial cells formed in the liquids of the sacs, the dark or brown colour of the liquid being in a ratio corresponding Tdth the amount of inflammatory products, e. Structure of the mceplwUnd-loolcmg matter, often found on inner surface of cysts, being composed of fibriUated tissue inclosing granular corpuscles, fat, and albuminous matter, d. Free fat in globules, e. Cholesterin. In the excess of the inflammation, the capillaries may have burst, and then, blood forms one of the ingredients. These various products, in their different combinations, give rise to the peculiarities of the contained liquids of the sacs, which vary as to colour, as is well known, from that of straw to that of dark chocolate. Ail these 804 THE cell: various appearances can be generally noticed in an ordinary case of this disease, and, in quite an extended series o^ cases which I have had the good fortune to study, I have never failed to trace clearly the epithelial epigenetic relations of the affection. It is not for me to say that cysts in this organ may not, and do not, sometimes, have another origin, being, as Rokitansky* observes, " new formations from the beginning.'-' But cystic disease of this nature I have never had the good fortune to observe, and I cannot easily conceive of its occurring in an organ such as the ovary, com- posed of only vesicles and stroma. Real carcinomatous disease of the ovary, attended with an enlargement of the Graafian vesicles, sometimes occurs, and we have an additional evidence of its real nature, in the fact that the same disease existed in other portions of the body. Such cases have been recorded by Baillie, Cruveilhier,t and Rokitansiy. But, without doubt, such cases are quite rare ; and, on those recorded cases, in which the presence of malignant disease was not met with in other parts, I cannot place much reliance ; for, in the more advanced forms of common cystic disease, appearances are observed having all the gross aspects of real carcinoma ; and some of the best pathologists of the present day have acknowledged that, trusting to gross appearances, they have been deceived thereby. This is a point which well might be enlarged upon with interest, for, aside from its importance, there could be well illustrated in it the advantages attending, in fact, the necessity, of the microscopic ana- lysis of all morbid products. At this late-hour of our labours it would not be proper to pause to vindicate, or even to urge, a course of inquiry, the truth of which we have necessarily taken for granted all the while. From its not uncommon occurrence, and its almost necessary fatality, epithelial epigenesis occurring in this tissue has an importance quite exceeding that of its occurrence elsewhere. These relations, however, are more of a practical nature, and I have desired to . look at the subject only in an histological point of view. Even in this light, I should not have discussed it thus fully, had I not felt the justness of asserting my claim for the priority of the view of the single nature of the cystio diseuse of the ovary, it always being an epithelial epigenesis of the Gfraafian vesicle.X * Rokitansky ; Pathol. Anat. Syd. ed. yoI. ii. p. 332. f Cruveilhier ; Anat. Path, du Corps Hnmain, &o. Paris, lib. v. X For a farther discussion of this interesting subject I may refer to an article of mine, illustrated by oases, Cystic Disease of the Ovary, as elucidated by Microscopical Inquiry, Charleston M#d. Journ. vol. vii. Jan. 1852, p. 27. ITS PHYSIOLOGY AND PATHOLOGY. 805 It now remains for me to notice, by way of conclusion, another form of cystic disease of the ovary, which is so allied with the pre- ceding that it may well be alluded to in this connection. I refer to those ovarian cysts in which are found hair, teeth, and sometimes hones. I have had a few opportunities to examine these piliferous cysts, and in every instance they had all the characteristics of en- larged Graafian vesicles. They were lined with an epithelial layer. When we consider that hair is, histologically, only metamorphosed epithelium, it is not diflScult to comprehend that it should sometimes arise as well in these localities as elsewbere. The facts as stated by Cruveilhier, that it is found in males, and also in other than sexual organs of the body, would lead us to conclude that it is to be regarded only as one epithelial epigenesis occurring within another, and having no essential dependence upon the ovary. Cysts of this kind have un- doubtedly a close relation with those constituting encysted dropsy of this organ ; and, from all I have seen, may be referable to the same causes. Of that other class of cases, coming, however, in the same cate- gory, in which teeth and pieces of jaw-bone are found in ovarian cysts, many curious examples have been recorded. It has not been my good fortune to see any of these cases, and concerning them, therefore, I am entitled to no scientific opinion. But this much I will say : that the time has now arrived when our knowledge of the relation of the sexes, based upon careful experience, enables us to justly take a decided view of the matter. With regard to the human female, the hypothesis that a new individual being, or parts of such (thus showing that a new individuality had at least com- menced), can be produced wittout the conjunction with the ovum of the .fertilizing fluid of the male, cannot, in the present state of science, be 'for a moment entertained. I well know that, in mp,ny of the remarkable cases recorded, the virgin aspect- of the sexual organs is strongly insisted upon. But in all these mattery, we must consider that it is unphilosophical to place an hypothesis founded upon state- ments of which we are not absolutely positive, against a view founded upon common experience and supported by all analogy.* • For cases of this kind deserving notice, see the following : Anderson, Ed. Med. and Surg. Journ. toI. ii. p. 180; Cruveilhier, Anat. Path. livr. xviii. andxxxvi. ; Aber- nethy, Med. Chirurg. Trans, vol. i. p. 35 ; Clapp, Lond. Med. Gaz. vol. xUv. p. 282. Also, Nouv. Diet, de M^d. et de Chirurg. Prat. art. Ovaire. 806 THE cell: II. Vascular Epigeneses. Under this head, I do not mean the new vessels formed in tumours of either a heteromorphous or a homoeomorphous nature, for such are direct prolongations of the normal vessels, and can only be regarded as morbid from the relations under which they are found. They exist in virtue of the law of congruity of tissues ; that is, there must be a nutritive supply, where the nutritive function is to be performed. Strictly considered, therefore, they are physiological and not patho- logical formations. Not so is it, however, with true vascular epigen- eses, which are found holding no relations of function. Such are the erectile tumours, collections, or little knots of bloodvessels, either venous or arterial, existing usually directly beneath the skin. They generally include in their midst a small quantity of areolar tissue, and are capable of a temporary erection like the ordinary erectile tissue. In almost every instance they are located somewhere on the upper portion of the body. In by far the majority of cases they are obviously congenital, and I think there is reason to believe that, in those few 1"^ stances where they seem to arise anew after birth, this is really not so, but is due rather to a sudden increase of that which has been formed congenitally, but so small as not to be perceived. We are, however, quite imperfectly acquainted with the morbid con- ditions on which these epigeneses depend. Like all morbid products, they appear to be, as far as I have examined them, infra-formations; and, although there are vessels, yet these are much less perfect than the healthy ones on which they rest. In an histological point of view they possess but little interest. When examined microscopically, after the tumour has been removed from the body, they will be found composed of vessels with quite tenuous walls, all bound together by a delicate areolar tissue, which shoots up between the meshes. This areolar tissue is an embryonic formation; that is, the common areolar tissue persistent on a low stage of development. The cells, therefore, are fusiform, and have not passed into true fibres.* * These tumours haye been known by several names — thus: Telangiectasis, HEema- toma, Haematoneus, Nsevus vasoulosus, Aneurysma per anastomosin, &o. &c. Its literature is very scattered, and I cannot here notice it. ITS PHYSIOLOGY AND PATHOLOGY. 807 III. Muscular Epigenesbs. The muscular tissue, as we have seen on a preceding page, is a true embryonic formation, and on this account we should not expect to find it subject to the morbid phenomena of epigenesis. This I believe is really the case. For, although possessing a well- marked nutritive energy, there is no evidence, as far as I am aware, that it is ever repaired after it has been removed by accidents or wounds. In all these instances, and especially when analyzed by the microscope, the tissue of repair has been found to be of a fibroid character, the true muscular element being absent. In regard to its real epigenesis in a distinct form, there is yet no evidence based upon direct observation that it ever occurs.* That it is thus produced, has been inferred from the consequences only. But for my own part, I am quite disinclined to admit it on such premises alone. In the instances where the voluntary muscles of the extremities or the muscular tissue of the heart become greatly increased in size, there is no evidence, based upon microscopical analysis, that this in- creased size is due to the formation of new fibres. .On the other hand, as far as I have examined the matter, it seems rieferable to the fact that the fibres, already existing, gain in size, exactly as we have seen to be the case with the increase of this tissue from the young animal to the adult. The enlarged volume of muscular tissue due to increased function, as in the instances of that of the heart and those of the extremities, is therefore properly not a pathological, but a physiological pheno- menon. It is an hypertrophy, rather than an epigeinesis. Those cases in which it has been asserted that this tissue is formed in exudations, and where the evidence that it is muscular tissue is not based upon a microscopic examination, I cannot for a moment admit as being worthy of consideration. They are probably founded on error, and, on an histological point of this importance, I should be quite unwilling to admit any but the very best evidence, f In regard to the epigenesis of the non-striated muscular fibre, * Since the above was written, I have met with two notices of the alleged appear- ance of true muscular fibres ; one by Rokitansky (Weiner Zeitschrift, 1849), in a tmnour of the testicle, the other by Virchow (quoted in Giuge's Atlas of Path. Histol. transl. by Leidy, p. 34), in a tumour of the ovary. t See MiiUer's Archiv, 1834, p. 451. 808 THE cell: Vogel* thinks it sometimes occurs, and has given figures represent- ing it. These appearances I do not remember to have met with in any tumours, and on that account I would not wish to appear to deny the fact of its occurrence. Still, if ever really an epigenesis, it is at least rarely so ; and much care is necessary in discriminating between it and certain fibroid tissues which are not uncommon, and which simulate very closely the appearance of organic muscle. IV. Nbevous Epigenesbs. What has just been said of the muscular, is quite applicable to the nervous tissue. It is an embryonic one, and one, too, having the same or even a higher physiological dignity. Its occurrence, there- fore, under abnormal conditions, would not be looked for. I am quite inclined to doubt if it ever is renewed after injuries.f It is true that the continuity is made up by a tissue seemingly capable of performing, to a certain extent, the nervous function, but there is no evidence that this tissue exactly resembles the true nervous tissue which has passed away. I know that this view is not acceded to by Steinruck,J Nasse,§ and others. Still, more careful and extended inquiries are needed ; and I feel pretty confident that, unless the cases be in very young individuals, the view of the non-reparation of true nervous substance will be found to be the correct one. In regard to real epigeneses of nervous tissue, we have as yet no good evidence that they ever exist. In the cases of hypertrophy of nerves, and the so-called nervous tumours {neuromata), the new tissue is not that of nerve, but one of a delibate fibroid character. Such, at least, has been true of some few cases I have had the good fortune to analyze microscopically. There is an additional reason why we should not expect the occur- rence of the true nerve-tube under these abnormal relations. It is this : We have seen that it is formed from nerve-cells, and these are originally formed from the vitelline globules ; and we should little look for the formation of these cells in the track of a nerve, and especially when the nutrition was abnormal. I do not wish to limit my views by my own experience ; still, I am not at all inclined to the opinion that new formations of true nerv- * Vogel, loc. cit. Amer. ed. p. 176, pi. iv. fig. 4, and pi. vii. fig. 2. t I refer here only to the human subject ; for, as is well known, and as I have my- self had the good fortune to observe, this tissue in common with the others is renewed in the restored parts of tritons, salamanders, &o. % Steinrtick ; De nervorum regeneratione, Berlin, 1838. § Nasse; Miiller's Archiv, 1839, p. 405. See also the same, 1840, p. 270. ITS PHTSIOLOfiY AND PATHOLOGY. 809 ous tissue ever take place, excepting, perhaps, in very young indi- viduals, -where the type-power of the tissue still persists to a sufficient extent* V. Cartilaginous and Osseous Epigeneses. Here we touch upon the ahnormal relations of tissues of less rank and physiological dignity, and we shall find them much more clearly marked and unequivocal in their nature. And although from- their intimate connection I have included them under a single head, yet we shall best look at them separately. 1, The Oartilotge Hpigeiiesis. — For the first description of this product in an intelligible manner we are indebted to MUller.f From both its chemical and microscopical peculiarities he gave it the very proper name of enchondroma. It is a true epigenesis, and con- sists of a product exactly resembling normal cartilage of the tran- sient form. By both Miiller and subsequent writers, it has been described as taking its origin both upon bone and in soft parts quite distinctly separated from it. Regarding it, as I do, as a true epigenesis, I cannot consider that it ever originates except in contiguity with its analogous tissues. For this reason,'! am inclined to distrust the statements of those authors who allege to have met with it in the interior of tumours and other soft tissues. The fact that, in almost every case of this kind, the evidence that the tissue in question was cartilaginous, was based-upon a gross, and not upon a microscopic examination ; this, I say, would be sufiBcient to lead me to distrust their conclusions, even was there no histological point at stake. ' Much less, therefore, should I be willing to accept any such assertions to be true, when, in so doing, I should be introducing a new feature into our vidsvs of the relations and powers of tissues ; for, as I have remarked on a preceding page, the declaration that a new individual tissue can arise per se in the midst of- tissues of a dissimilar nature, is pretty much the same as asserting the doctrine of spontaneous generation. * At the end of these remarks upOn the epigenetio relations of the muscular and nerrous tissues, ire might properly take up the consideration of the subject, of the regeneration of lost parts in the lower animals. The relations of this process and that leading to epigeneses in general are somewhat similar ; but then again they are different, the one (epigeneses) being due to an asthenic, while the other (regeneration) to a sthenic condition of the type-power of tissues. t Miiller ; Ueber den feineren Bau der Gesohwulste, Berlin, 1838, pp. 31-49 ; or West's translation. VOL. VI.— 52 810 THE CELL: The number of even all the alleged cases of this kind is quite small, and a very small proportion of these were examined by the microscope.* In these few cases, I am inclined to the opinion that, as is often true of encysted tumours, they had, originally, a connection with the analogous tissue ; but which growth, and change of form and size, had finally quite obscured. As usually occurring, its favour- ite locality is about the joints of the hands, and it may be said without exaggeration that nine out of ten of all the cases recorded have betn upon these parts. Vogelf makes a distinction between cartilaginoug exostosis and true enchondroma, and thinka that true enchondromata do not ossify, they being the fibrous form of cartilage. My own experience does not warrant this distinction, and as yet we seem quite unacquainted with the conditions leiading to ossification in these products. Removed from the body, the incised surface pre- sents a smooth, semitranslucent, turnip-like aspect. Under the microscope, appearances usually quite like those of normal cartilage are seen ; a granular or semi-fibrous stroma, in which lie cells which are nucleated and irregular in aspect. m '■^r^