HENRY KIMPTON , MEDICAL BOOKSELLER 82,H1GH HOLBORN , LONDON, W.C.. ON THE STEUCTUEE AND GEOWTH OF THE TISSUES. C Bf02 BPAXV2 'H AE' TE'XNH MAKPH . ON THE STRUCTURE OF THE SIMPLE TISSUES OF THE HUMAN BODY. WITH SOME OBSERVATIONS ON THEIR DEVELOPMENT, GROWTH, NUTRITION AND DECAY, AND ON CERTAIN CHANGES OCCURRING IN DISEASE. A COURSE OF LECTURES DELIVERED AT THE 0f Hfrgsirians 0f APRIL, MAY, 1861, LIONEL S. BEALE, M.B., F.R.S., * PHYSIOLOGY AM) OV GENERAL AMD MOBBIO ANATOMY III KING'* COLLEGB, LOHDOR. WITH 70 FIGURES AND A DESCRIPTIVE LIST OP 61 SPECIMENS. LONDON: JOHN CHUECHILL, NEW BURLINaTON STEEET. d& LONDON : PRINTED BY HARRISON AND SONS, ST. MARTIN'S LANE, w.c. PKESIDENT, FELLOWS, MEM-BEES, AND LICENTIATES OF THE ROYAL COLLEGE OF PHYSICIANS, PKEFACE. ALTHOUGH the observations recorded in the follow- ing pages have necessarily led the author to give expres- sion to a general view or doctrine which seems to him to account for the appearances observed, he thinks it right to state that the conclusions which have now assumed a definite form have gradually grown upon him during the course of observations extending over a period of several years. In fact some of the drawings in this volume, and others which have been published else- where, equally favorable to the view, were made long before any specific theory had been arrived at. An attempt has been made to account for the anatomical characters of certain tissues and to trace the changes which take place during the development, growth, nutrition, and decay of individual textures. The results obtained, it need scarcely be said, are very Vlll PREFACE. incomplete, but they are quite sufficient to encourage the author to pursue more extended observations in this direction. There is every reason to believe that as* our knowledge of the minute alterations occurring in the elementary parts of tissues increases, the views now generally held upon the nature of the healthy and morbid changes occurring in the organisms of the higher animals and man will become much clearer and more simple than they now are. The author believes that the numerous facts he has brought forward and the drawings which he has published will be considered sufficient to justify him in opposing the views generally entertained on the structure of the connective tissues. Although the con- clusions arrived at are very different from those generally entertained in Germany, it must be borne in mind that observers in that country are by no means agreed upon the elementary facts upon which the connective tissue theory may be said to rest. For instance, Kolliker's explanation of the appearances observed in tendon, and his description of the formation of the so-called cells and intercellular substance in this structure, in cartilage and in bone, by no means accords with those of many other authorities. The author has not attempted to give all the opinions entertained on this and other matters, or to show in what points he agrees with or differs from previous observers, for had this plan been followed out the pre- sent volume would have been twice its size and would probably have found very few readers. Indeed the author fears that the detail into which he was forced PREFACE. ix to enter on the subject of the connective tissues will be devoid of interest to many of those who nevertheless are exceedingly fond of anatomical investigation. He is however quite ready to discuss the matter more in detail in German periodicals if his fellow-workers in Germany desire it. The author has devoted much time during the last twelve years to the preparation and demonstration of tissues. Although he feels quite certain that the processes he has adopted will be very much improved, he cannot but believe that the preparation and preser- vation of specimens of the tissues of vertebrate animals, in which both capillaries and nerve fibres are very distinctly demonstrated, many of the latter being less than the 1 -50,000th of an inch in diameter, with the germinal matter (cells and nuclei) of all the different tissues stained with carmine, is a step in advance. Moreover, many of the points delineated in the draw- ings can be clearly demonstrated in the portable micro- scopes even to large classes, and it is certain that specimens which require the highest magnifying powers (700 to 1,700 diameters) will also be capable of class demonstration when the mechanical adjustments of the portable microscopes have been made more delicate. The tissues, of which illustrations are given, have been hardened so that very thin sections were readily obtained, without resorting to the processes of boiling or drying. Some of these preparations even give one the idea that more would be demonstrable if a higher magnifying power could be brought to bear on them. The highest power which the author has yet been able PREFACE. to obtain is the 1-2 6th of an inch, made by Messrs. Powell and Lealand, magnifying 1,700 diameters. The preparations described in the descriptive list of specimens and most of those figured in the plates are in the author's possession, and he will be happy to show them to any one who desires to examine them. Some anatomists have sought occasion to disparage those who, as they think, waste so much time in mechanical operations and manual work, while other eminent men have assailed as worse than useless the process of injection and other methods of preparation. It seems to the author that all future advance in minute anatomy must depend upon improvements in the methods of examination. The fact has not been generally recog- nised that the soft delicate tissue which forms the terminal portion, and is in reality the active part, of nerve, becomes altered immediately after death, and by the action of water many soft structures are at once destroyed. The only hope therefore of ascertaining the arrangement, and of forming a true notion of the action of the most important tissues of the body is in the discovery of plans of investigation which shall prevent the breaking down and disintegration into granular matter which immediately follows death. The only means of effecting this seems to be the rapid impreg- nation of the tissue with some fluid which at once arrests disintegration, and how is it possible that tissues can be so equably, quickly, and thoroughly im- pregnated with a preservative fluid, as by the process of injection ? The Lectures, which have in part appeared in the PREFACE. XI Archives of Medicine, the descriptive list of the speci- mens, of which copies were distributed in the lecture- room, and drawings of some of the specimens, have been collected together in the present volume in a complete form. It is believed that readers will be able to gain in an hour or two a general notion of the author's views if they will carefully examine the drawings with the aid of the explanation which precedes them, and refer to the general remarks and summary on page 178, as well as the description of the specimens exhibited, which commences on page 1. The author has spared no labour in trying to make the drawings faithful copies of the objects. A sketch was first made upon paper, and the size of the several objects carefully measured, next this rough outline was transferred to the wood block, and the drawing finished on the block itself from the object placed in the microscope. For the skill and accuracy with which his drawings have been engraved, the author is indebted principally to Miss Powell. Figs. 57 to 67 were engraved by Mr. Williams, and Plate IV by Mr. Wragg. 61, GROSVENOR STREET, September 16$, 1861. LECTURES ON THE STRUCTURE AND GROWTH OF THE TISSUES OF THE HUMAN BODY. Delivered at the Royal College of Physicians, 1861, By LIONEL S. BEALE, M.B., F.R.S. LECTURE I. Introductory. Importance of various methods of preparing MR. PRESIDENT AND GENTLEMEN, THERE are few subjects connected with modern medicine of greater interest than the one which I have your permission, Sir, to discuss in this course of lectures. The study of the structure and growth of the tissues is enticing from the great questions it comprehends, and is worthy of being prosecuted with the utmost diligence and earnestness, because many of the facts elucidated in the course of such an enquiry cannot fail sooner or later to become of great practical importance. I shall only attempt to bring under your notice a very small part of this extended enquiry, and shall restrict myself mainly to the anatomy of the simplest tissues of the body. I wish I was able to give you a complete history of the life of but one of these tissues, and describe the changes which occur during its development and growth, and the alterations which take place when the conditions under which it lives are modified, 18 THE STRUCTURE AND GROWTH alterations which, although quite inappreciable when they commence,, may end in the destruction of the tissue, and the death of the organism. Although I am fully conscious that this is quite beyond my power, some advantages will, I think, result, if we study the anatomy of tissues from this point of view. The history of the changes which occur in man from the commencement of his existence to its natural close, is a history which can never be made perfect, and there is reason to fear that but few chapters will be written until long after the youngest enquirer now living will have been compelled to cease from bis labours. We can hardly hope to see the outline of such a work as this firmly established on well ascertained facts but how could our time be more usefully employed than in collect- ing and arranging materials, and urging 011 by every means in our power, researches, the results of which may contribute to form the outline of a story which as yet hardly commenced will, let us hope, be handed to our successors in a more complete form ? Such a history will advance with every age, and though it can never be perfected by human power, will always afford instruction, and be read and meditated upon with advantage, especially by those whose duty it is to test its assertions, correct its errors, and add to its completeness by new observations. The difficulty of these enquiries is indeed great, and it is seldom that the hoped-for practical application of the results of scientific investigation is obtained until long after the work has been completed. Still, experience has proved that the observer may feel quite confident that at some time or other all earnest work will be productive of useful results. There are some who are constantly struggling to prove by reiterated assertion rather than by simple evidence, how little practical benefit is likely to result from all the scientific work which others love to prosecute. It is possible that men, who by this systematic disparagement apologise for their own dislike of labour, are the involuntary instigators of that which they desire to retard, for in all ages unreasonable opposition OF HUMAN TISSUES. 19 has been the unwilling, but not the least efficient, means of rapidly establishing truth on the firmest possible basis, and extending it far and wide. Any one who fairly compares the principles on which disease is now treated with those generally accepted even fifty years ago, cannot fail to observe a wide difference. Dogmas were laid down by authority, where now the merest tyro can only be influenced by reasons, and the clever theories of the cleverest thinkers were appealed to as the basis of practice, while in the present day a more solid founda- tion is being slowly, but let us hope, surely established, by submitting every opinion to the searching tests of observation and experiment. Were the elements of physical science as generally taught as the elements of arithmetic we should not have to deplore the influence exerted by the table-turners, spirit rappers, and the whole class of medical impostors. These men live by flattering the conceit, and fostering the ignorance of people who have never learned to think. They fear truthful investigation, and hate the diffusion of knowledge. Is it not painful to think that persons highly educated in some branches of learning, should listen attentively to this nonsense, and be utterly blind and deaf to all the inexhaustible wonders by which they are surrounded, which the human intellect is specially adapted to investigate, and the contemplation of which is a never failing source of happiness, which increases as life advances, and often retains its freshness long after the organs with which we have worked and experimented have grown old in our service, and must rest from their labours ? By encouraging to the utmost of our power the study of physical science, we shall be more serviceable in protecting the public, since every man acquainted with the elements of physical science would protect himself, from imposition, than by endeavouring to increase the stringency of our laws. It is, I confess, miserable to see in many instances with what effrontery and tact the charlatan, well acquainted with B 2 20 THE STRUCTURE AND GROWTH the weaknesses of mankind, imposes on the credulity of those he pretends to serve, and successfully hides his determined ignorance, his idleness, and his heartless greediness ; but it is more miserable, and almost hopelessly disappointing, to hear it asserted that in our own ranks there are a few individuals so devoid of self-respect, and so utterly benumbed to all that is serious and good and true in medicine, as to submit to the farce of a consultation with such a one, and thus by one single act bring on us a disgrace which the courage and self-devotion of hundreds of perhaps less successful, but more honorable men will hardly obliterate. Advance in medicine has at all times been so intimately associated with, if not absolutely dependent upon, the pro- gress of certain collateral sciences, especially anatomy and animal chemistry, that it is to be regretted that these pursuits are not more generally prosecuted by physicians than they are at present, in this country. When we consider how medicine has been advanced by such men as Harvey and Hunter, is it not surprising that scientific investigation in connection with medicine is not carried on under the superintendence of the physician to a much greater extent than it now is ? I believe that this is in great measure to be attributed to serious defect in what ought to be an important department in all our hospi- tals. Many physicians must have felt the want of well arranged scientific work-rooms where various microscopical and chemical investigations could be carefully carried out under their direction. I am so sanguine as to hope that the time is not very far distant when this defect will be remedied and the principle generally recognized, that we should prosecute scientific investi- gation, in order that we may discover new truths which will certainly, though perhaps not at the moment, be productive of practical good, as well as afford what relief we can to present suffering. In the minds of some persons there is undoubtedly an im- OP HUMAN TISSUES. 21 pression that such enquiries cannot be conducted without disadvantage to the patient,, and there is a tendency in the public mind to draw a distinction between the so-called practi- cal doctor who cures the ailment with a single dose, and the scientific man who, like a dreamer and useless speculator, thinks and theorises, but is not up to the direct means of giving relief to a patient in pain. We are, however, all aware how much we have learnt during the last few years from the investigations into the secretions in health and disease, which have been lately carried on both in this country and on the continent, and there can be no doubt that if careful researches could be prose- cuted on a larger scale in our public Institutions great advance would very soon be manifest. I think we should make every effort to establish such a department in connexion with our large hospitals, for surely, besides endeavouring to relieve the ills of our contemporaries, a very important part of our duty is to work out and enforce principles which when acted upon may increase the physical development and mental vigour, and largely contribute to the happiness of those who are to follow us. In thus urging the importance of scientific investigation in its minute details to practical medicine, I am not ignorant of the difficulties with which the effort is surrounded, and had I not had some practical experience I should not have ventured to allude to the matter here. I have felt the disap- pointments, regretted the wasted hours, and sighed over the useless results of many days' hard labour ; and like every one who has worked in this direction, have in my possession volumes of observations which have led to nothing, and long analyses from which no reliable inferences can be drawn. For seven years I worked and taught in a laboratory which I had arranged close to the hospital; and although of late I have been engaged in work of another kind, I am now looking forward to an opportunity, which will I hope soon be afforded me, of carrying out on a larger scale chemical and microscopic 22 THE STRUCTURE AND GROWTH work bearing on medicine, which was commenced while a student, and in which I shall endeavour to take an active part as long as I have health and strength to work. I have ventured to make these remarks because I cannot help feeling that, till within the last few years, an impression has been gaining ground, and is even now, I fear, too generally diffused, not only amongst practitioners but among students, that minute investigation tends to make us unpractical, and that work in the laboratory and in the museum is antagonistic to the study of disease in the wards of an Hospital. It seems to me that we ought, all of us, to make an effort to oppose very strongly such statements, which are most positively contra- dicted by the history of those who have led the most useful professional lives. This disparagement, I am quite sure, has discouraged many from prosecuting serious and useful work who would otherwise now be advancing the best interests of their profession, and employing their spare time in a manner most advantageous to themselves, instead of feeling dissatisfied with their progress, and perhaps discontented with their profession. Surely the earlier years of professional life cannot be more use- fully or more happily spent than in prosecuting some branch of scientific inquiry in connection with our profession, and cer- tainly there can be no more fitting preparation for the great work of our lives than the practice and continual study of medicine. During the last few years, the love for such work seems to have revived, and if the taste is as widely diffused and encou- raged as this College desires, the position which we shall occupy iu Europe and America as prosecutors of scientific medical inquiry will not be inferior to that which is generally accorded to us in questions relating to the practical treatment of disease. It is far from my intention to obtrude upon your notice in very positive terms the conclusions to which I have been led by my investigations, or to lay down dogmatically my own interpre- tations of observations, and ask you to accept them ; nor shall OF HUMAN TISSUES. 23 I uphold my conclusions by bringing forward all the facts and arguments I can in their support, for I am most anxious that you should examine the preparations from which my inferences have been drawn, and consider if v the arrangement you observe can be explained on any other view. The doctrine which I shall advocate has resulted solely from observation, and I did not enunciate it until about a year since, when the accumulation of facts became so considerable that I thought myself justified in attempting to frame a theory which should serve to account for the appearances I had observed, which I could not explain by the view generally entertained. Some of my conclusions are at variance with the opinions generally held, especially in Germany, and in bringing them forward I am, I think, fully sensible of the difficulties which all observers have experienced, and I trust that the plain manner in which I shall discuss some of these questions will not be construed into disrespect for the opinions of those who entertain opposite views. I would not have placed myself in this position had I not fortunately succeeded in making preparations, and also in preserving them, so that they may be examined by any one desirous of doing so, and with the highest magnifying powers which have yet been made. The difficulty of understanding many of the views now held, and the still greater difficulty of teaching them, are, I think, alone sufficient to justify the reconsideration of the whole question of the minute structure and growth of the tissues. There is no branch of scientific enquiry in which general conclusions have been so many times altered as in that which relates to the anatomy and mode of growth of the different tissues and organs of the body, and in proposing a view which, as far as I can judge, accounts for a greater number of observed facts than those generally entertained, I am fully conscious that, as investigation advances, it may be necessary to modify it in many important particulars. I believe that it will be found to possess a temporary usefulness, and to whatever charges I 24 THE 8TRUCTUBE AND GROWTH may be exposed in bringing forward another view, I think I am free from the charge of increasing the difficulty of explaining some of these complex phenomena, and proposing new and difficult terms, the meaning of which cannot be easily denned. I hope that the points which I shall endeavour to establish may assist us in the attempt to determine what phenomena taking place in living beings are dependent alone upon physical and chemical actions, and may enable us to distinguish these from the changes which are dependent upon powers which every living being has inherited from those from which it sprung, and may transmit to its successors j and which are peculiar to every different kind of creature. The only terms which are not generally used in quite the same sense in which I shall employ them are the following : Elementary parts, into which every structure may be divided. A. particle of epithelium is an elementary part. The elementary part consists of matter in two states. Germinal Matter. Matter in a state of activity, or capable of assuming this condition, possessing inherent powers of selecting certain inanimate substances, and of communicating its properties to these, exists in all living beings, and from it every tissue is produced. I propose to call this germinal matter. A certain portion of the germinal matter of many elementary parts is comparatively quiescent, but is capable of assuming an active state at a subsequent period These portions are the so- called nuclei and nucleoli, and new nuclei and nucleoli will make their appearance within them when they have grown into ordinary elementary parts. The matter on the external part of every elementary part exists in a passive state, as Formed material, which was once in the condition of germi- nal matter, but it has now ceased to be active. It cannot communicate its powers to lifeless matter. Its composition, form, and properties depend upon the powers of the germinal matter which it often protects. OF HUMAN TISSUES. 25 Secondary deposits These are insoluble matters which vary in form and composition in different cases, and may be con- sidered, in some cases, to consist of formed material, which has been deposited amongst the germinal matter, instead of only external to it. Deposits may accumulate to such an extent as to cause the germinal matter to form a very thin layer between them and the formed material. These points will, I think, be at once understood by reference to the following diagrams. Fig. l. a. The smallest visible particles of germinal matter, b. Small collections ol germinal matter, with a little formed material between them (as in mucus). In one, portions are seen to project, and if these were detached each one would grow and give rise to new masses, c. Germinal matter with a very thin layer of formed material on its external surface (cell wall), d. Same as the last, but with a new centre of growth now comparatively quiescent, but capable of assuming active growth (nucleus) appearing in the germinal matter. If c were exposed to unfavourable external conditions the whole would be destroyed, but under similar circumstances the nucleus of d might alone resist these influences, and the conditions becoming favourable would grow and produce new elementary parts, although all but this small portion of the germinal matter had been destroyed. e. A thick layer of formed material, the whole of which was at one time in the state of germinal matter. /, Secondary deposits commencing to appear amongst the germinal matter, as fatty matter is precipitated amongst the germinal matter of the fat vesicle, g. A further stage of the same process, h. Separate masses of secondary deposits as in the starch-holding vegetable cells, i. Deposition of formed material or secondary deposit in successive layers on the inner surface of the original capsule, but leaving spaces or intervals in which currents are con- tinually setting in opposite directions during the life of the germinal matter. k. Germinal matter and formed material which is granular, the particles of which are becoming resolved into several substances as takes place in the ele- mentary part of the liver (liver cells). 1. Formation of fibres from germinal matter, m. Germinal matter belonging to, and taking part in the formation of, the walls of a tube. 26 THE STRUCTURE AND GROWTH The task I have proposed to myself is a difficult one. To demonstrate to another the minute points upon which the different views are based, is not always easy when the micros- cope is fixed and the illumination is as perfect as can be obtained ; but I shall attempt to demonstrate some exceedingly delicate structures under some of the highest powers that have been employed in the examination of the tissues of man, and the higher animals, and to pass the microscopes round the room so that every one may have an opportunity of seeing some of the specimens from an examination of which my con- clusions have been drawn. Should my arrangements at first not work quite so satis- factorily as I hope, I trust you will forgive me for having made the attempt. I must now ask your attention to the arrangement of the microscope, by which I hope the object we have in view may be effected. The instrument is made after the manner of a telescope with draw tubes; the object is fixed across a stage below the object glass by a spring which presses against the back of the slide. By this arrangement I can easily place any part of the specimen under the object glass, and by means of a little screw-clamp I can fix it firmly in the exact spot I wish. The object is brought into focus by screwing down the middle draw tube to the proper position, and the more exact focussing is effected by drawing the tube to which the eye-piece is attached backward and forwards. It will be observed that in this arrangement the preparation is held firmly in its place, and it is scarcely possible to alter its position if ordinary care be used. You would hardly expect that an apparatus so simple as this would enable us to examine objects with very high powers, but I shall presently show you objects under the tenth and twelfth of an inch object glasses, which I trust will at least enable you to form some idea of the structures I shall refer to. Most of the questions to which I shall advert are very difficult to decide, and an opinion can only OF HUMAN TISSUES. 27 be formed after long and careful observation of many specimens of the same structure, so that I cannot hope to be able to convince you of the truth of my inferences,, although I trust I shall succeed in proving to you that they are not unreasonable nor improbable. The little microscope is firmly fixed in this stand which is provided with a small oil lamp giving a good light.* Fig. 2. a. The lamp. b. The slide in which the foot of the lamp moves It is fixed in its position by a small screw, c. The stage of the microscope, d. The stand in which the instrument is firmly held. e. First draw tube. /. Focussing draw- tube, g. Slide in which the lamp is placed when objects are to be examined by reflected light. The instrument and stand were made for me by Mr. Matthews, of Portugal Street, Lincoln's Inn. The focus may be altered by drawing the tube to which the eye-piece is attached in and out, until the object is seen perfectly clear. Each microscope is numbered, and the number corres- ponds with the number in the "Explanation of the objects" which has been distributed. (Page 1 to 16.) In the preparations which I shall show you the part of the tissue which is active, and which possesses the most wonderful powers of increase, is tinged of a dark-red colour by carmine, which has been much used in Germany for filling tubular structures by capillary attraction. This I have termed germinal matter, and it exists in all living beings, and at every stage of their growth, but its proportion varies according to the age of * This instrument is fully described in No. VIII of the Archives of Medicine. 28 THE STRUCTURE AND GROWTH the tissue. The youngest tissues consist almost entirely of germinal matter, while in the oldest textures little exists. Those tissues which grow rapidly and change much, contain a large proportion of germinal matter, while, connected with those which grow very slowly comparatively little is found. The tissues of the body which possess such different properties were all once in the condition of germinal matter, and the characters or properties which the tissue possesses in its fully developed state, depend upon the powers of the germinal matter from which it was formed. Tissues which are remark- able in their adult state for the large quantity of the so-called inter-cellular substance, exhibit but little during the early period of their development, while in their earliest condition they may be said to consist of cells alone. At first there is no inter-cellular substance at all. The tissue or formed material is not coloured by carmine, and if by prolonged maceration it be stained by it, the stain may be removed by soaking in glycerine, but the tint still remains in the germinal matter. This is a most important and very remarkable fact, and is observed in the tissues of every living being I have examined. Many difficulties have occurred in attempting to colour some textures, but these have been in a great measure surmounted, and I believe that in every living being, by the action of an ammoniacal solution of carmine, and subsequent soaking in glycerine, we can positively distinguish the germinal matter from the formed material, the active living matter which after passing through certain definite stages of existence, will become formed material, from the formed material already existing. The same general statements already made, apply with remarkable accuracy to morbid growths. Those which grow rapidly consist of much germinal matter in relation to the proportion of formed material, while those of very slow growth contain matter capable of being coloured by carmine in small amount. I shall have to refer more particularly to the relation of the formed material to the OF HUMAN TISSUES. 29 germinal matter in my next lecture, and I shall allude to some very remarkable effects produced by the carmine. In most of my preparations the capillaries have been filled with a transparent Prussian blue injection, containing a little alcohol and chromic acid ; so that at the same time that the vessels are filled with colouring matter, the adjacent textures become permeated with a fluid which entirely prevents any tendency to decomposition, and many transparent albuminous textures are rendered just sufficiently granular to enable us to see their arrangement distinctly. By these methods of preparation several minute points have been determined, such as the relation of the cells of the liver to the terminal branches of the duct, the ultimate distri- bution of nerve fibres in several different tissues, the structure of the ganglia of the sympathelic, the relation of the terminal branches of the nerves to the dentinal tissues. Nerves have been readily traced and microscopical ganglia demonstrated in the fibrous tissue of the pericardium, in the submucous tissue of the epiglottis and pharynx, in the transverse fissure of the liver, and in the substance of the tongue, the formation of bone and dentine has been studied under the highest magnifying powers ; and by following out the same plan I have reason to hope that some of the most difficult anatomical questions may be decided. Not the least advantage of the process is, that the tissues may be preserved permanently and subjected to exami- nation with the highest powers. You will find from the remarks I shall make, that I have been led to differ in opinion upon some very important ques- tions, from many of the highest authorities. We shall have to consider, for instance, whether certain appearances depend upon the presence of solid bodies in the tissues, or are spaces con- taining fluid, whether certain delicate lines are fibres or tubes, which is the oldest and which is the youngest part of a tissue, and of each component part, and a great number of questions 30 THE STRUCTURE AND GROWTH which one would think could be very easily decided, but which really prove most difficult to determine. As to the offices performed by tissues, you will also find my conclusions altogether at variance with those generally arrived at, and to such an extent, that in tissues generally, a structure which I believe to be inactive, (the so-called intercellular sub- stance), has been considered to be the seat of positive form- ative power; and, on the other hand, that which I believe to be the actual seat of the vital changes, has been deemed the least important part of the tissue, and perhaps even merely acci- dental (the nucleus in certain instances, the so-called cell in others). Such questions can only be determined by an appeal to the preparations, and I hope to be able to convince you that many of my conclusions are justified by the appearances pre- sented by the specimens which have been prepared by the process I have adverted to. Let me now show you some preparations which illustrate the general points which are brought out in various textures by the method of preparation which I have devised, and I shall ask you to compare these specimens with parts of the very same tissues prepared in a different manner. I am sorry thus to trouble you with what may seem very uninteresting practical detail, but I think you will find that many of the discre- pancies in the statements of different observers, arise simply from the different manner in which they have subjected the specimens to examination. In fact I think it will be found that many of the most difficult questions can only be solved by studying very carefully the circumstances under which the tissues in question may be examined so as to display their characteristic peculiarities in the clearest manner pos- sible. I have been careful to select specimens for illus- trating these points, which are likely to prove interesting to you on general grounds, so that we shall lose no time unnecessarily. OF HUMAN TISSUES. 31 No. 1. An injection of some simple papillae of the human tongue under a magnifying power of 130. Three separate ones are seen. The epithelium has been removed and the capillaries are seen fully injected with Prussian blue. Oval bodies, con- sisting of germinal matter,, tinged bright-red with carmine, pass in various directions in the papillse, and are very numerous at the summit of each. Of these oval bodies, tome are connected with the capillary vessels, but the great majority, I shall en- deavour to prove, are connected with the nerves which form a sort of network lying on the surface of the capillary vessels, and embedded in a transparent tissue. No. 2. Is a thin section removed from the central part of the tongue of a white mouse, prepared as the last specimen, under a power of 215. The muscular fibres are observed with capillaries ramifying over them. The oval nuclei are principally connected with the capillaries and nerves, but these points require a much higher power for demonstration. These specimens illustrate the general appearance of the capillaries when injected with Prussian blue, and the oval bodies when stained with carmine, according to the plan I have described. No. 3. Is a thin section from the tongue of a mouse just killed. It is placed in a little very weak glycerine, and magni- fied 130 diameters. It contrasts remarkably with the last specimen. The smaller vessels cannot be discerned. Nuclei are seen, but very indistinctly, and in smaller number than they exist. The want of definiteness about the structure, would cause you to conclude that in this specimen, areolar or con- nective tissue predominates over every other tissue, and you would be led to conclude that the nuclei are connected with the fibres of the areolar tissue, although you could not see an absolute connection between the fibres and nuclei. No. 4. Is another specimen from the central part of the tongue of the mouse, from the same part as the last section, but injected and soaked in carmine. The f connective tissue' of the last specimen is seen to contain numerous capillaries and 32 THE STRUCTURE AND GROWTH nerve fibres. The nuclei seen in the section are clearly con- nected with the nerves and capillaries. Nerve fibres, not more than the one ten-thousandth of an inch in diameter, can be traced to and from the ganglion. The nuclei on the surface of the ganglion usually considered as the nuclei of the connective tissue surrounding its cells, belong to the nerve fibres which grow from the cells. This specimen is magnified 250 diameters, and in another lecture I shall show parts of this preparation under powers of 700 and 1,700 diameters, and hope to demon- strate the real nature of the connective tissue and its relation with other structures. There is, however, no organ which enables me to illustrate the importance of different processes of preparation so well as the liver, and as the structure of this gland is of the utmost interest to all of us, in connexion with the derangements taking place in disease, I could perhaps hardly select an illustration which would be more useful. The anatomy of this gland has long been one of the most vexed questions in anatomy, and of late the opinion has been gaining ground that the ducts terminate amongst the cells, which do not lie within tubes or follicles, as in all other true glandular organs in the higher animals. Hence this organ has been placed in the class of glands without ducts, and removed from the category of true glands. Upwards of six years ago I succeeded in injecting the ducts of the liver, and believed that I had demonstrated that the ducts were immediately continuous with tubes containing the liver cells, a view which had been held by several observers, although no one had succeeded in proving the point by specimens. I regarded the liver as the most perfect type of gland, because the largest quantity of secreting structure and blood were brought into the closest relation, while they occupied the smallest possible space. It appeared to me that the relations between the blood and the secreting cells, was the most perfect which could possibly be devised to fulfil the ends in view. My preparations proved to OF HUMAN TISSUES. 33 me that injection passed directly from the ducts into a network of tubes with very thin walls, which were occupied with the liver cells. The coloured injection passed between the cells, and the walls of the tube, insinuating itself through very narrow channels, but nevertheless forcing its way along these tubes for a considerable distance, and sometimes it reached the centre of the lobule. As I could force injection thus artificially in a direction the reverse of that in which the bile flows during life I considered that the possibility of the bile flowing between the walls of the tube and the cells fully proved, and that it was quite unnecessary to assume that it was passed on from cell to cell, a process which is not carried on I believe in any organ whatever. These conclusions were published in a paper in the Phil. Trans., in 1856. The investigation is so difficult that I ven- tured to express the opinions I had arrived at in terms which some writers have slightly misunderstood, and they have given me credit for feeling more doubt on the subject than I actually had. However, after an interval of nearly seven years I can now speak with far greater confidence. There are probably few anatomical points more difficult to demonstrate to others positively than this, and it is therefore only right that- one should allow full weight to the investigations of those observers who have been led by them to form a different opinion, and I am most desirous of doing so, but I was not pre- pared for finding a drawing copied by myself as nearly as possible line for line from one of my preparations, distorted in such a manner that it never could be recognized as indicating in the least degree the appearances which actually exist. Prof. Budge of Greifswald, gives me credit for so gross a misrepre- sentation of an actual appearance that I fear he must at least think me very blind or very prejudiced, or perhaps both. I did not believe that any one who was himself accustomed to microscopical work would have considered that the merest tyro 34 THE STRUCTURE AND GROWTH could have made such a mistake,, as the one which I am credited with by this Professor. However, here is my drawing of the specimen, and here is Prof. Budge's inference from my drawing of the appearance of the specimen which he has never seen, and I now pass round the preparation itself, which was made seven years ago (5). It is magnified 215. You will see the blue injection amongst the cells in the tubes, and not the faintest indication of the tubes around each cell, which Prof. Budge states he has seen, and feels convinced exist in this specimen. I hope to have the pleasure of affording to Prof. Budge some day a similar opportunity of comparing the specimen with the drawing.*" No. 6 is a corresponding preparation from the human liver magnified 130, showing the ducts just at the edge of a lobule, and their continuity with the tubes of the cell-containing network. No. 7 is also from the human liver, and shows the capil- laries injected blue, and the cell-containing-network alternating with them, and having in all parts of the lobule exceedingly thin walls, but quite distinct from the capillaries. This pre- paration is magnified 215. Perhaps, however, the most perfect demonstration of the cell-containing-network, and its continuity with the ducts is obtained from the examination of the liver in cirrhosis, in which disease the cells and tubes shrink, the change com- mencing at the portal aspect or circumference of the lobule, and proceeding gradually towards the centre. No. 8 is a section of a healthy liver under an inch object glass. The portal vein was injected with carmine, and the hepatic vein with Prussian blue. The capillaries of the lobule are filled with the colouring matter those in the centre of * I have made many injections with the chromate of lead and every other opaque injection I could lay my hands on, and have stated that I always failed. Professor Budge does not seem to have tried the plan which I employed for preparing my own specimens. OF HUMAN TISSUES. 35 each lobule being blue, while those at the circumference are red. Observe how very narrow the interlobular fissures are, and how in many places the capillaries of one lobule are con- tinuous with those of adjacent lobules. The interlobular spaces are clearly destitute of any areolar or fibrous tissue. They are occupied by the branches of the portal vein which you see, and branches of the artery and duct, and lymphatics, which have not been injected in this specimen. Let this specimen be com- pared with the cirrhose liver (No. 9), in which the vessels have been also injected. What a wide space exists between the contiguous lobules, of which but very little, and only of the central part of the lobule, remains in many cases. Vessels arid tubes, which will be seen more distinctly in another specimen, are observed in the substance of the tissue usually stated to be fibrous. No. 10 is a specimen of a cirrhose liver, magnified 130, soaked in carmine, and now you can see the shrivelled cells within the narrowed tubes, and the network so distinctly, that you will hardly fail to wonder how it has happened that the nature of this so-called fibrous tissue had not been made out long since but many of the most delicate and beautiful textures appear fibrous enough when placed in water and roughly examined, and thus morbid changes have been supposed to originate in a really passive structure, the areolar or connective tissue. No. 11 is a specimen from the same liver put up in water, and not a vestige of anything but e fibrous tissue ' is to be seen where we now know numerous tubes and cells and vessels are actually to be demonstrated. By immersing a delicate prepara- tion in water, I can often produce the appearance of the presence of a large quantity of fibrous or connective tissue. These specimens will, I think, serve to satisfy you of the great importance of preparing tissues, for I have clearly proved that many structures ordinarily invisible may be demonstrated c2 36 THE STRUCTURE AND GROWTH most distinctly by certain special processes. I might have taken illustrations from almost any other tissues of the higher animals,, or from the lower animals or plants, but I have chosen those which seemed to bear most directly upon that department of microscopical enquiry, which is of the greatest interest to us as practitioners of medicine. OF HUMAN TISSUES. 37 LECTURE II. Of the Structure of the simplest Living Beings. MR. PRESIDENT AND GENTLEMEN, LET me suppose a physician, with plenty of time at his disposal, who had a love for work, and was anxious to study the nature of any disease. Such a man would continually feel desirous of ascertaining the actual changes which are going on in the organisms of his patients while they were under observa- tion. He would very soon find that it was absolutely necessary to work at physiology and pathology, or he would not feel in a position to prosecute any special enquiry. Now he would find the greatest difficulty in coming to anything like a con- clusion with regard to questions which clearly must be positively settled before he could proceed. He would thus be driven to work at the minute anatomy and chemistry of textures in disease, and soon he would discover that many fundamental questions of mere anatomical demonstration had not been determined, and the most conflicting views as to the order of growth of textures and their action, would prevent him from feeling any confidence in his work. Next he appeals to the healthy structures, and now he is dismayed at finding that we THE STRUCTURE AND GROWTH are not sure how nerves terminate in various tissues, and, while in chemistry he finds the indefinite term ' extractive matters 7 applied to a considerable quantity of matter, of the nature of which he can learn very little, so in anatomy he hears of areolar or fibrous tissue, or indeterminate tissue, existing every- where, and especially abundant in the very situations in which he would expect to find nothing unnecessary, and the arrange- ment of the tissues of the most beautiful character, according with the wonderful delicacy of the offices to which he knows them to be subservient. He looks for some general explana- tion of the appearances he sees, and he finds cells described in works, and delineated with most distinct cell- walls, contents, and nuclei, but when he comes to examine the tissues, it is but seldom he detects anything answering to the ordinary description of a cell, and with respect to so simple a structure as cartilage, he can scarcely find any two observers who agree as to the meaning of the appearances observed. He enquires how a tissue grows ; which is the oldest part, and which the youngest ? how food becomes tissue ? where inanimate matter becomes living ? what is actually living, and growing, and changing, and what has ceased to live and change, and has grown to its full dimensions ? Every one who has thought earnestly on medicine during the last few years, must have frequently asked himself these questions. Let us suppose such questions now asked, and before we proceed further in the enquiry, and in order that we may get them answered in the simplest and clearest manner, let us appeal in the first instance to one of the simplest living structures we are acquainted with, common mildew. I have described at some length the changes taking place in this structure, and propose now to refer very briefly to the results.* We shall afterwards be able to discuss with better chance of success the general anatomy of the tissues of the higher animals, and we shall be able to examine the cell theory and other * Archives of Medicine, No. VII, page 179. OF HUMAN TISSUES. 39 doctrines proposed to account for the formation of the structures of which living beings are composed. Let us try to make out the history of the life of this simple living structure, and consider how its growth and other charac- ters are influenced by conditions somewhat different to those under which it grows most favorably. The consideration of the changes occurring during its development and nutrition is extremely interesting. When we attempt to examine the structure of the simplest forms of living beings, we cannot but regard the extreme minuteness of many independent organisms which live, and grow, and increase their kind, with the utmost astonishment. We shall scarcely be able to realise this minuteness at all. When I watch the appearance of minute organisms in water containing a little dead animal or vegetable matter, I feel sure that many of the living particles were in existence some time before they had grown large enough for me to see them with the highest power I have been able to obtain (1,700 diameters made by Messrs. Powell and Lealand). So also in all other living beings, the living particles by which the active changes are effected, are, there is reason to believe, far too small to be seen. Of the structure of such organisms and particles we have as yet learnt nothing by direct observation, but from carefully investigating the structure of larger bodies closely allied to these, as ordinary mildew for instance, some conclusions as to the manner in which growth takes place may be arrived at. I have been led to certain inferences with regard to the structure of these simple forms of life, to which I shall now very briefly allude. As I shall have very frequently to refer to these points in the course of the ensuing lectures, I must ask your careful attention to them. I shall endeavour to prove that growth in all living structures occurs in the same manner, that the matter to be animated passes in the same direction in all, and 40 THE STRUCTURE AND GROWTH that the living particles invariably pass through certain stages of existence, and end by giving rise to material totally different in composition to the living particles. This may be further altered, but it cannot reassume its former characters, properties, or powers. The difference in the results of the life of different living organisms depend upon their powers, and these they have derived from their predecessors. Living particles cannot be distinguished from each other by microscopical observation, and in consequence it is utterly impossible, from the structure of a living particle, to predicate its office, or, so to say, the results of its living, nor to tell whether it has belonged to one of the lowest or highest organisms, to an animal, or to a plant. When I use the word living, I employ it in a general sense, and mean that active changes, some of which can be explained by physics or chemistry, while others cannot, are taking place, or are capable of taking place, under favourable conditions ; and by dead, I understand matter which has already undergone these changes, and which is brought again under the uncon- trolled influence of physical and chemical forces. The shaft of a hair, and the particles of the epithelium on the surface of the cuticle, are just as dead before they are detached from the body as afterwards, but there are constituent elementary parts of every age leading uninterruptedly from these dead particles which have no power of increase to those which have only just commenced their existence, which are nearest the vascular surface, and are undergoing rapid multiplication. Now it is as impossible to indicate the precise moment at which a living particle ceases to be able to produce particles like itself, as it is to announce positively the day or hour of our lives when we cease to ascend towards the highest point of vital activity we are to attain, and begin to decline. I shall, however, I hope, be able to describe some of the important changes which take place in the elementary parts as they grow, and I shall contrast with each other elementary parts of different ages, from the OF HUMAN TISSUES. 41 same tissue. Every elementary part consists, as I have already stated, of germinal matter and formed material which was once in the state of germinal matter. Just as in the cuticle, on the surface of mucous membranes, and in certain glands, elemen- tary parts exist of every age, so every tissue and organ in the body is composed of elementary parts in every stage of exist- ence, and arrangements exist by which the oldest formed material may be removed. Some formed material is resolved into simpler compounds, and removed very soon after its form- ation ; while in certain tissues the formed material is of a very permanent character, and it is doubtful, if in certain cases the formed material which now exists in our bodies will not remain in much the same state as long as we live. Most important changes may be brought about by the fluid in contact with this formed material. In health it is bathed with a fluid which preserves its integrity ; but in certain cases the composition of this fluid is so altered that the formed material undergoes changes closely resembling those which may be induced in it artificially, if kept at the temperature of the body, in a fluid which will not protect it from the influence of oxygen. Under these circumstances it may undergo most important changes ; but these points will be more fully discussed, when the general anatomy and order of growth of the healthy tissues of the body have been considered, and I only now allude to them for the purpose of showing at once that we must not look upon disease as a condition essentially different and separated by a distinct line of demarcation, from the healthy state, but rather look for a disturbance in the rapidity of the processes of multiplication and decay of the elementary parts, and alteration in the composition of the fluid which brings to them nourishment, or which prevents the uncontrolled action of destructive agents on the formed material. If the spore or any segment of the stem of a simple fungus be examined, it will be found to consist of an external capsule, enclosing some very transparent matter. The outer THE STRUCTURE AND GROWTH capsule is comparatively firm, and hard and unyielding; but the internal substance is soft, perhaps almost diffluent, and is easily destroyed. It may be washed away and removed, while the external capsule will retain the same characters which it possessed before it was disturbed. You will say at once the external membrane is the cell-wall, and the material within, the cell contents, while the distinct particles amongst the contents are nuclei. Let us, however, for the present avoid all terms which involve theories, and consider how these parts are formed in these simple structures. The new matter is certainly not added on the external surface, for if this were the case the outer membrane would increase in thickness, while the mass within would remain of the same size as when it was first seen. In some instances the outer membrane increases in thickness, and the matter within also increases, but sometimes the outer mem- brane remains very thin, while the matter within is seen to undergo a considerable increase. After the whole mass has reached a certain size, it divides and the process is repeated in each of the resulting structures. Very soon perhaps millions of minute organisms are produced. When this division does not take place very rapidly, the external membrane of each particle is observed to increase in thickness, and generally, it may be said that the slower multiplication occurs the thicker this becomes. Is the new matter added just within the outer membrane? If this were so, at one time matter like that of which the mem- brane is composed would be formed, and at another, the inne r soft material must be produced. It would follow, too, that in some cases the material must be entirely converted into the one sub- stance, and in others it must give rise alone to the development of the other. The increased thickening of the external mem- brane is often produced at the expense of the inner matter. Is the external hard material formed within the substance of the envelope itself? This question has been already included in a previous one. From a consideration of numerous observa- tions, I feel convinced that the new matter, the pabulum, the OF HUMAN TISSUES. 43 nutrient material, which is about to become a part of the living mass, passes through the external membrane, and amongst the particles of which the central mass is composed. I believe it passes into the interior of these particles, and having been brought into very close contact with their component particles, becomes endowed with the powers they possess, and is then living. The doctrine to which I have been led is shortly this, that the smallest living particles, of all living beings, are spherical, and I believe these are composed of spherical particles ad infinitum. The inanimate matter passes into the spherical particles, and there becomes endowed with their wonderful powers, in fact becomes living. The living spherules move in a direction from the centre towards the circumference of each spherule to which they belong. Their tendency to divide is due to the same force which compels them to move constantly from the centre where they became living. Each particle is preceded by those which became living before it, and succeeded by others which were animated since it commenced to exist. This movement out- wards occurs in the living particles of all living beings, and its rapidity determines the rate at which the structure grows. The particles in passing outwards, gradually lose their power of animating matter, and at last having arrived at a considerable distance from the centre, where they became living, undergo most important changes, and are resolved into substances having properties very different to those which the living particles possessed during the earlier periods of their existence. The particles now cease to move, they lose their active powers, and perhaps coalesce to form a firm hard substance like the external membrane of the mildew, or they may become resolved into compounds which are completely soluble in fluid, which are perhaps very soon decomposed into substances of a much simpler composition. This outer substance, resulting from changes occurring in the oldest particles of the inner matter, I propose to call formed material, and the living matter within, which may increase in the most rapid manner, which gives rise 44 THE STRUCTURE AND GROWTH to every tissue, and is in fact the growing living part of every structure, from which all new structures originate, I shall speak of as germinal matter. The characters of the formed material depend upon the powers of the particles of the germinal matter, and it is affected by the conditions under which these grew. The powers of the germinal matter depend upon those of the germinal matter which gave it origin. As the composition of the formed material depends entirely upon the properties of the germinal matter which produced it, the sub- stances resulting from the disintegration of the formed material, and the compounds resulting from the action of oxygen on these are peculiar, and differ materially from each other, just as the properties of the formed material differ in the various tissues and in different living beings. It is, therefore, very doubtful if these substances will ever be produced independently of living matter. Undoubtedly if the component elements could be brought within the sphere of each other's action under the same conditions as in the living organism, the same compound would result, but as these conditions cannot be brought about artificially, and cannot be conceived to exist except in living bodies, this is not saying much. It would, I think, be as inconsistent with the advances science has now made, to conclude that these compounds can be produced artificially, as to believe that man, by arrangements of conditions within his power, will at length succeed in producing a living structure. Every living particle can alone spring from pre-existing particles, and every particle of albumen, casein, fibrin, &c., is produced under con- ditions which can only exist in living particles. In many cases certain of the particles of the germinal matter grow more slowly than others and remain perhaps for a long period in a comparatively quiescent state. These collections are generally spherical or oval, and they have a power of re- sisting the action of external circumstances which would destroy the active portion of the germinal matter. These are the so-called nuclei, and from them new structures may spring OF HUMAN TISSUES. 45 even if the germinal matter in which they lie be destroyed. When they become active, certain minute particles within them may become new nuclei, while the particles of the original nucleus increase and pass through the various stages of their active existence, and at last become resolved into formed ma- terial. Generally, when the conditions under which an ele- mentary part is placed are very favourable for the growth of the germinal matter, the most rapid increase in size may be observed to occur in the particles just within the envelope of formed material, and not unfrequently numerous spherical masses of germinal matter may be seen in close contact with the membrane, and therefore as near as possible to the nutrient matter. In some cases, after a layer of formed material has been produced externally, and the whole mass has reached a certain size, certain particles of the germinal matter become resolved into formed material, which collects as one mass, or in the form of several separate granules or globules, which may accumulate amongst the particles of the germinal matter. If this process continues for some time the germinal matter forms a thin layer between this mass of formed material, which I propose to call secondary deposit, and the outer membrane or envelope of formed material, a position in which the germinal matter (primordial utricle) of the vegetable cell and that of the fat vesicle (nucleus) are found. The composition of formed material in the centre of the mass is not the same as that surrounding it, but not unfrequently they are composed of substances closely related to each other. From these remarks you will infer that one essential change taking place in living particles is a constant motion from centres, and the constant formation of new centres from every one of which infinite growth may take place. This power of infinite extension is restricted within due limits by circumstances which we shall take the greatest interest in studying, and I 46 THE STRUCTURE AND GROWTH shall have occasion to draw your attention to cases in which these restrictions are diminished to a considerable extent, and, in consequence, structures which we know as morbid growths or formations result. Regarding a growing spore of mildew as an elementary part, it consists externally of formed material, within which is the germinal matter. Certain portions of the germinal matter are not in a state of great activity like the remainder, and these are nuclei from which new growth may proceed if the formed material and the remainder of the germinal matter should be destroyed. If there are no nuclei no future elementary parts can be formed, and the death of the germinal matter renders it impossible that new structures can result from the mass. The structure of mildew is seen in No. 12 x 700, and No. 13 x 1,700 diameters. Alkaline colouring matters have no effect on the formed material, but colour the germinal matter very strongly. In some very interesting specimens, coloured by immersion in an ammoniacal solution of carmine, obtained from certain fibrous textures, which I sliall show you, there is no distinct line of demarcation between the germinal matter and the formed material. Most externally is the formed material quite colourless, then comes a layer of very young and imperfectly hardened formed material, which is slightly tinted ; next, germinal matter, darkly coloured, and amongst this, nuclei most intensely coloured. The structure which is most in- tensely coloured is farthest from, and that which is not coloured at all, in immediate contact with, the colouring matter. The carmine can be made artificially to pass through the layers of formed material unaltered by them, to the germinal matter, where it becomes precipitated, probably in consequence of the acid reaction of the germinal matter. Am I not, therefore, justified in inferring, that inanimate matter, OF HUMAN TfSSUES. 47 about to become living, pursues a similar course, and that every living particle increases by growth from centre to circumfer- ence, the oldest portion of each spherical component particle being external, the youngest,, that which was but just now inanimate matter, in the centre ? 48 THE STRUCTURE AND GROWTH LECTURE III. Of the Tissues of the higher Animals and Man. What is a Cell ? The Cell and other theories. MR. PRESIDENT AND GENTLEMEN, IN my last lecture I endeavoured to show that mildew, and all such simple living structures, were composed of matter in two states, germinal matter and formed material. I endeavoured to prove that the formed material, of which the external envelope was composed, was once in the state of germinal matter, and that the inanimate matter, which formed the pabulum or nutrient substance, passed through the outer covering of formed material into the germinal matter, in the particles of which it became living. Here all those wonderful powers, which the germinal matter itself possessed, are com- municated to the inanimate particles. I brought forward facts to show that the germinal matter was composed of spherical particles, and these of smaller and still smaller spherules. I believe that these spherical particles always move in a direction from centre to circumference. The formed material differs as much from the germinal matter in its structure as in its properties. The germinal matter alone grows and is active, and can alone animate inanimate matter. The properties of the formed material depend upon the powers of the germinal matter from OF HUMAN TISSUES. 49 which it was produced. These powers were derived from the germinal matter, which gave it origin, and so on from the beginning. The germinal matter possesses the power of infinite growth, by which statement I mean, that this material will continue to increase as long as it is placed under favourable conditions and supplied with the proper pabulum or nutrient substances. The germinal matter is coloured by alkaline colouring matters, especially by carmine, while the formed material remains perfectly colourless, although it is much nearer to the coloured solution than the germinal matter. I hold that we are not able to form any opinion as to the size of the smallest particle capable of independent existence and endless increase, but I feel sure that the smallest living particles we can yet discern have been growing for some time before they were large enough to be seen through our most perfect micro- scopes. We have now to consider how far these conclusions are applicable to the tissues of the higher animals. However large and complex the organism may be, it is very easily separated into certain parts or organs which are set apart for the performance of distinct offices. The body of a vertebrate animal contains, as we all know, bones, muscles, fat, the liver, kidneys, the brain, and nerves, &c. Each of these may be resolved into elementary organs. An entire bone may be regarded as consisting of an assemblage of certain small portions, each of which contains every structure essential to the constitution of bone, and necessary for its growth. A lung, or a kidney, or the liver, may, in the same manner, be show n to consist of elementary lungs, kidneys, or livers, although these cannot always be perfectly isolated. In different animals, the size of these elementary organs differs, but not to the same extent as their number. An organ of a large animal, like the whale, differs from the corresponding organ of a small one like the mouse, enormously as to the D 50 THE STRUCTUKE AND GROWTH number of elementary organs of which it is made up, but in a much less degree as to the size of each of these. Each elementary part is composed of several structures having very different properties. An elementary lung is com- posed of a delicate transparent membrane, with elastic tissue, vessels, a prolongation of the bronchial tube. These structures are themselves compound. Connected with the smallest arteries we find nerve fibres, elastic tissue, muscular tissue, and epithelium. The nerve fibres, muscular and elastic tissue, and epithelium, are composed of elementary parts, and each element- ary part consists of matter in two states, germinal matter, active and growing, capable of multiplying itself, formed material, passive and incapable of multiplying itself, which was once in the state of germinal matter. An elementary part of the liver in the same way is composed of the germinal matter within, and the formed material externally, the outer part of the formed material is gradually altered, and at last resolved into bile and a substance easily converted into sugar. An elementary part of bone consists of a mass of germinal matter, external to which is formed material, which gradually becomes impregnated with calcareous salts from without inwards, channels (canaliculi) being left, along which fluids pass to and from the germinal matter in the centre, which gradually becomes inclosed in a space (lacuna) . An elementary part is seldom more than the 1 1000th of an inch in diameter, and frequently it is very much less. In the adult organism it is often difficult to recognise the ele^ mentary parts in all cases, in consequence of changes having occurred in the course of their growth, but in the early life of every creature they are distinct enough in every tissue. In the higher animals these elementary parts are arranged in certain collections which possess very different endowments. In some of the simplest living beings the entire organism may be regarded as consisting of one elementary part. OF HUMAN TISSUES. 51 Every elementary part comes from a pre-existing elementary part ; but it does not follow that its endowments are to be the same as those of the elementary part from which it sprung. We must not look upon the elementary parts of a tissue as bodies which, having assumed a definite form and reached a certain size, remain perfectly stationary, but as structures which are continually undergoing change not a single particle of which they are composed is still. It is true the movements occur so slowly in some as to be imperceptible, except after long intervals of time ; while we can scarcely conceive the rapidity with which change takes place in others. But movements must occur in all, and they take place in the same direction. The elementary parts, which we examine in our microscopes, were undergoing change just before they were removed from the living structure. We have stopped the changes at a certain point, and, as the ages of the elementary parts differ materially, by carefully comparing the appearances in several, we may obtain, after numerous observations, data which enable us to form something like a connected history of the life of one of them. These elementary parts are usually termed cells, and the cell is defined as an organ, consisting of a wall permeable to fluids, with certain contents within, and usually, but not con- stantly, a nucleus. In the process of secretion it is believed that certain materials pass through this wall into the interior of the cell by endosmose, and then become altered by powers existing in the cell or resident in the nucleus, and, having undergone conversion into new substances, pass through the wall of the cell by exosmose, and constitute the special secretion. In tissues it is believed that the cell exerts a peculiar action on the matter which surrounds it, by reason of which this manifests or becoms endowed with certain peculiar and characteristic properties. It is the exception rather than the rule to find that the contents of a cell are in a fluid state, and when this is so, numerous living particles are suspended in it. In the liver D 2 52 THE STRUCTURE AND GROWTH cell the contents are certainly tolerably firm. In the kidney cell they present the same characters. Their consistency gene- rally is such that it is impossible to conceive the flowing in and out which is imagined. Again, if endosmose continued for a time, and then the contents remained stationary, and afterwards exosmose occurred, we ought to be able to see the alteration in the size of the cells taking place within a very short period of time ; but no such change has been observed. It is difficult to conceive endosmose and exosmose occurring at the same moment at all parts of the surface of the cell wall, for the physical conditions which would lead to the one are absolutely incompatible with the other. Cyclosis in plants has been accounted for by endosmose ; but it would, I think, be impos- sible to cause any particles to pass round and round a closed vesicle in a constant direction by currents flowing in towards the interior from every part of the surface. There are other difficulties in the generally accepted theory which would be tedious to follow out, and, as I shall endeavour to prove the absence of the membrane as a constant structure, it is unneces- sary to detain you by endeavouring to show that the changes occurring in the formation of secretions could not be explained by endosmose and exosmose through such a structure, sup- posing it to exist. According to the generally received theory, the cell wall is considered a most important structure; but it does not exist constantly. There is a very large class of the lower animals from whose bodies protrusions may be formed in different parts, and these protrusions may meet here and there. Where they touch, they coalesce. Clearly, then, there can be no investing membrane here ; neither is a living structure of this kind confined to the lower animals. It exists in man himself. I have seen such protrusions from mucous particles both from the nose and also from the bronchial tubes, under a power of 1,700 diameters. A portion of the mass slowly extends itself out- wards ; perhaps three or four such outgrowths may be OF HUMAN TISSUES. 53 seen in different parts of the mass. If detached, they assume the spherical form ; but if two come into contact they coalesce. These movements only lasted for a minute, or less, after the mucus was transferred to the glass slide. Protrusions may be often observed to occur from the white blood corpuscles, and in rare cases the red blood corpuscles adhere so intimately to each other that it is difficult not to believe that the outer part of their walls consists of a viscid matter undergoing soften- ing which runs together when several come into contact.* It is clear, therefore, that the cell-wall is not a constant structure, and that living organisms and elementary parts of living organisms, may exist without it. Again, in the younger, so-called cells, of the cuticle, contents and a cell-wall are figured and described by authors generally ; but in the old cells, the contents become altered and incorporated with the wall in a manner which has not been explained. The liver-cell is usually appealed to as an excellent example of a cell ; yet who has proved the existence of a membrane ? Seven years ago, long before I had attempted to form any general views of structure, I tried to prove the existence of this cell-wall ; but utterly failed, and was obliged to mention this in my work on the liver, f No. 14 shows the appearance of elementary parts (cells) from the liver of the mouse, Many contain two of the so-called nuclei, and some contain three or four. Nuclei are observed of all sizes, and the amount of formed material is very different in the different masses. In some elementary parts, the outline is sharp and well-defined ; in others, it is rough and angular ; and in some, the outer part seems to be undergoing disintegration. No cell-wall is to be demonstrated around these masses. The outermost part of the formed material gradually becomes dis- integrated and resolved into soluble substances. The largest of the so-called nuclei are, in fact, becoming elementary parts ; * A case is mentioned, and a drawing given, at page 264, of the " Microscope in its Application to Clinical Medicine." (2nd Ed.) t " On the Anatomy of the Liver of Man and Vertebrate Animals," 1856. THE STRUCTURE AND GROWTH and what would be called their nucleoli would then become nuclei. Some of the masses are very irregular in shape, angular, and often much elongated, as if they consisted of soft material which had been moulded in a tube. In No. 15, elementary parts from the liver of an old man, aged 74, are seen. The liver appeared healthy. The elementary parts are, for the most part, small ; and there is not that very distinct line of demarcation between the germinal matter and the formed material which was seen in the last specimen, and which is in part due to the method of preparation. Oil-globules and particles of colouring matter have been precipitated amongst the formed material. No. 16 contains elementary parts from a cirrhose liver. The quantity of formed material here is much greater than in the last specimen ; depending partly on the difficulty to the free escape of the bile caused by the wasted contracted state of the tubes of the network at the outer part of the lobule. But, you will say, there can be no doubt as to the cellular nature of the red blood corpuscle ; this is admitted by all to consist of a membrane with certain fluid coloured contents. A nucleus is to be demonstrated in some, although not in the adult human blood corpuscle. The opinion generally received is certainly that the human red blood corpuscle is a cell with red contents, the nucleus of which has disappeared, or else it is the free nucleus of a cell, and here the question is dismissed. But the blood corpuscle may also be regarded as a corpuscle consisting of matter of different density in different parts, being firm externally, but gradually becoming softer, so as to approach to the consistence of fluid towards the centre. Dr. Dalton, of New York, has expressed this opinion of the structure of the blood corpuscle in his published lectures ; and I believe some few other observers entertain similar views. I have never succeeded in seeing the cell-wall said to exist, neither have I been able to confirm the oft-repeated assertions with regard to the passage of liquid into the interior of the OF HUMAN TISSUES. 55 corpuscle by endosmose, its bursting and the escape of its contents through the ruptured cell-wall. When placed in some liquids, many of the corpuscles swell up and disappear ; but I have never seen the ruptured cell-walls. The red blood corpuscles from the same animal differ in character in a much greater degree than observers generally seem disposed to admit. Some are darker and harder than others. Some are so trans- parent as to be invisible without the greatest care, and cor- puscles may be found which are not more than the fifth or sixth of the size of an ordinary blood corpuscle. I have failed in my attempts to colour the red blood corpuscles drawn from capillaries or from a vein with carmine, but I have succeeded in colouring many in clots taken from the vessels after death ; and, in some instances, certain of the corpuscles within the capillaries of a stained tissue have been coloured. These cor- puscles were very much smaller than the white corpuscles, which are always very readily coloured, and did not exhibit the well-known granular appearance characteristic of the latter. I infer, therefore, that they were young red-blood corpuscles. The majority of the red-blood corpuscles of the human subject are certainly not to be coloured by carmine by employ- ing the same process as that by which the white corpuscles are always so readily coloured. The granular or nucleated cor- puscles of the embryo are readily coloured. The nuclei of the corpuscles of the frog become coloured ; but the external portion which is coloured naturally is not tinged by carmine. In winter the capillaries of the frog contain numerous oval corpuscles surrounded by a very thin layer of the external coloured por- tion, so that they are not more than half the dimensions of the corpuscles when the animal is active. I conclude, therefore, that the nucleus of the frog's corpuscle consists of germinal matter, and the coloured portion of formed material; and that when the animal is active, this formed material is gradually being dissolved away at the surface, while new formed material is produced from within; the oldest part of the formed 56 THE STRUCTURE AND GROWTH material being at the surface of the corpuscle, the youngest in contact with the germinal matter from which it was formed. Of the red corpuscles of mammalian animals, some are destroyed by certain chemical reagents which have scarcely any action on others ; and they are not all altered in the same degree or with the same rapidity by the action of water, weak alcohol, syrup, and various fluids, which probably only produce a physical change. Neither do all the particles in a drop of blood undergo the same changes immediately after it has been drawn from the living body. I think the red corpuscles of man are formed from the germinal matter of the white corpuscles. A particle set free in the current of the blood would appropriate the nutrient material and would grow. During this period it would be coloured by carmine. Gradually, however, the formed material increases, and the germinal matter in the centre dies. The corpuscle now undergoes another series of changes. It begins to be dis- solved away at the surface, and at last is, without doubt, entirely converted into substances which are dissolved by the serum, and its place is taken by a new corpuscle. But the fact which seems to me to prove most conclusively the nature of the mammalian red-blood corpuscle is this: Guinea-pig's blood, as is well-known, crystallizes very readily in tetrahedral crystals, and, if the process be carefully watched in a drop of blood which has been treated with a very little water, and covered with thin glass, and sometimes even without the addition of water, certain corpuscles will be seen to become angular, and four or eight prominent angles will be observed, while others will exhibit the stellate appearance familiar to everyone. In this remarkable case, then, the entire blood corpuscle may be seen to crystallize. I have seen one corpuscle gradually become one tetrahedron. Now, how can there be a membrane here ? The whole process seems inconsistent with the existence of such a structure. The crystals coalesce and larger crystals are formed ; but no mem- OF HUMAN TISSUES. 57 branes can be seen. Two crystals may come into close contact and gradually become incorporated, which could not take place if they were invested with a membrane. It is true, that some of the blood corpuscles are incorporated in the crystalline mass, and may be seen for some time amongst the red crystalline matter, but these are entire corpuscles I conclude young ones, not merely cell-walls. These facts permit us, I think, to take a very simple view of the development, nature, and offices of the red -blood corpuscle, which will, I believe, prove substantially true, but I must apologize for this long digression, and postpone the further consideration of this very interesting question. In the kidney, and indeed in many other structures, there is the same difficulty in satisfying oneself as to the existence of a cell- wall. The well-defined outline exhibited when elementary parts are placed in water, which is received by many as evidence of the presence of a cell-wall can be exactly imitated artificially. The urea having been separated, filter off a little of the remain- ing stituents of urine with the extractive matters, and when this solution is moderately concentrated, add nitric acid, so as to be quite sure that no living structures can exist, evaporate the mixture to the consistence of syrup and you will very frequently find a number of bodies, which might be readily mistaken for cells. It would be very instructive to make a series of such artificial products in different ways, for you would find many forms closely resembling the so-called animal cells. Such facts as these, and the changes which he has observed to take place in particles precipitated from fluids, have caused Mr. Kainey to come to the conclusion, I think prematurely, that the growth of bone, and even of some of the soft tissues, may be explained on physical and chemical grounds alone.* These observations of Mr. Rainey's are most interesting, and most important, and I shall have occasion to refer to them * " On the Mode of Formation of Shells of Animals, of Bone, and of several other Structures by a process of Molecular Coalescence, demonstrable in certain artificially formed Products," by George Rainey, M.R.C.S. 1858. 58 THE STRUCTURE AND GROWTH again when we come to discuss the anatomy of bone and teeth, but in all these tissues I have no difficulty in demon- strating the existence of living matter, and without this living matter the tissue never could be formed. Indeed, I may, without fear, assert that, in every living tissue there is germinal matter and formed material. The germinal matter may die, when the formed material has reached a certain thickness ; but I maintain that this formed material was, in all cases, once in the state of germinal matter, and could never have been pro- duced except as the result of changes taking place in living particles. Although in many structures it is difficult to prove the existence of a cell-wall, in others there can be no question as to its presence. In the mildew it is distinct enough ; but you may have observed that in the rapidly-growing parts of the plant the layer was exceedingly thin so thin, that its existence could hardly be demonstrated ; while in other specimens the thickness of the formed material was very great indeed. In the first instance the germinal matter was rapidly extending itself. In the last, in consequence, probably, of the existence of con- ditions adverse to the free growth of the plant, the germinal matter had slowly undergone conversion into formed material a certain amount of nutrient matter was absorbed, so that the whole mass had increased in size, but had the con- ditions been favourable, many times the quantity of formed material would have been produced in the same period of time, but this would have extended over a very much larger surface, and of course a very much larger proportion of germinal matter would at the same time have been formed. I need not detain you by describing the cell theory, as generally received in the present day, for no doubt you are all well acquainted with the doctrine. I have endeavoured to show that in some instances a cell- wall exists, and that in many there is no cell-wall at all, while in others it is impossible to distin- guish between the cell-wall and the so-called cell contents. OF HUMAN TISSUES. 59 The idea of Schleiden, accepted by Schwann, that the nucleus was precipitated from a fluid like a crystal, and the cell-wall afterwards deposited around it, has been often contradicted by actual observation, and it is difficult to see what object could be fulfilled by such a process. A modification of Wolff's view has lately been strongly advocated by Prof. Huxley, and has been made by him to harmonise with the notions entertained with regard to the nature of the intercellular substance. It is supposed that originally a clear homogeneous plasma is produced, in which spaces (vacuoles) are formed, and these contain, in the interior, the endoplast, consisting in fact of the primordial utricle of the vegetable cell, the cell contents, and the nucleus. The walls of these spaces are composed of the original plasma altered, which is termed the periplast, or periplastic substance. The greatest importance is attached to the periplast. It is supposed to possess the active power of growing in and forming partitions, when division of the endoplasts occur, and of becoming differentiated into very important structures. The intercellular (periplastic) substance is considered throughout Germany as a most important structure, and it is generally believed that its peculiarities are not dependent upon the cells it contains, but are due to powers residing in it. Mr. Huxley's views may be gathered from the following extract : " The endoplast grows and divides; but, except in a few, more or less doubtful cases, it would seem to undergo no other morpho- logical change. It frequently disappears altogether ; but, as a rule, it undergoes neither chemical nor morphological meta- morphosis. So far from being the centre of activity of the vital actions, it would appear much rather to be the less important histological element. " The periplast, on the other hand, under the names of cell- wall, contents, and intercellular substance, is the subject of all the most important metamorphic processes, whether morphological or chemical, in the animal and in the plant. By its differentia- 60 THE STRUCTURE AND GROWTH tion, every variety of tissue is produced ; and this differentiation is the result, not of any metabolic action of the endoplast, which has frequently disappeared before the metamorphosis begins, but of intimate molecular changes in its substance which take place under the guidance of the ' vis essentialis,' or to use a strictly positive phrase, occur in a definite order, we know not why." Virchow, on the other hand, attaches the greatest importance to cells, which always come from cells, but believes, nevertheless, that, tf It is not the constituents which we have hitherto con- sidered (membrane and nucleus), but the contents (or else the masses of matter deposited without the cell, intercellular), which give rise to the functional (physiological) differences of tissues." The cell is " a simple homogeneous and very monotonous structure, recurring with extraordinary constancy in living organisms." It is the other contents, not the nucleus or membrane, which occasion the physiological action of parts. Virchow considers that the nucleus is concerned in maintain- ing and multiplying living parts, and that while fulfilling its functions it remains itself unchanged. Dr. Hughes Bennett, of Edinburgh, holds, on the contrary, that cells can grow from a clear exudation, and he considers that granules first make their appearance, and that a cell- wall is afterwards formed around these. It is very difficult to express briefly the differences and resemblances between all these conflicting views ; and it would be quite out of place, in a course like the present, for me to show in detail the several points in which I agree with, or differ from, those who have written before me. I hope, therefore, these authorities will not think I am treating them with dis- respect if I allow the points of difference to appear from time to time as they naturally arise, instead of devoting much space to mere controversional writing, which could fulfil no useful purpose. My own conclusions do not permit me to agree with any of OF HUMAN TISSUES. 61 these theories. I have already alluded to the difficulty of demonstrating the existence of a cell-wall, and have shown that this is not a constant structure. So far from regarding the intercellular substance as the seat of essential changes, I shall endeavour to show that it is the least active part of the tissues, and that it does not possess formative power at all. Neither do I think that cells effect any alteration in the substance external to them. Living structures are, I believe, quite incapable of exerting any important action on matter at a distance from them. I cannot think that the cell (elementary part) can be formed from a fluid exudation, but believe with Virchow, that in all cases cellular elements must have existed wherever cells are found. I believe that every organic com- pound in the body was once living, or was derived from a living structure. Albumen in the blood, as such, is not living, but it has been formed by living matter, and may again become living, if appropriated by a living structure. Let us enumerate a few of the appearances connected with the structure of elementary parts which may be readily demon- strated, and for the explanation of which we are endeavouring to frame a theory. If what I have said with reference to the characters of germinal matter, and the order in which growth takes place, be true, as I hold it to be, for every living structure, any theory proposed should be equally applicable to all these different phenomena ; and if it will not account for them it should at least not be incompatible with any one. 1. The presence of a distinct membrane (cell-wall), perme- able to fluids, forming an investment to each elementary part, and containing within clear transparent or granular matter, at rest or in motion. 2. The absence of any such membrane over every part of the surface, so that protrusions occurring from different parts extend to a considerable distance, and where they come into contact, coalescence takes place, and then the most varied forms are produced. 62 THE STRUCTURE AND GROWTH 3. A very thick external investment, perfectly homogeneous, granular, or in distinct layers, varying in thickness and density, or resembling each other in these particulars. 4. The formation of insoluble substances, as well as the presence of matter in solution amongst the living matter within the external membrane. 5. The presence of a large or small quantity of a peculiar material, homogeneous, granular, deposited in laminae, or fibrous (intercellular substance), between the so-called cells or nuclei. 6. The absence of such a structure. 7. Elementary parts with nuclei and nucleoli, or destitute of both. 8. The formation of fibres projecting from the envelope of the elementary part. 9. The formation of fibres clearly prolonged from the sub- stance of the elementary part, and composed of the same structure. 10. Elementary parts may begin their existence as minute masses of granular (germinal) matter. At a later period a membrane may be demonstrable. Afterwards the membrane may become very thick indeed, so that a small cavity alone remains in its centre. I might very much increase the length of this already long list, but it is, I think, sufficient to prove that the doctrines at present taught will not explain all the phenomena which are observed ; indeed, some of the facts mentioned are alto- gether incompatible with the favorite theories now enter- tained. An elementary part may commence its existence as a very minute granule, too small to be seen even with the highest powers. It grows, and then exhibits an outer portion of different character to the material within. Changes may then occur in the inner material. Small bodies may appear, from which new growth may proceed at a subsequent period, and OF HUMAN TISSUES. 63 within these smaller particles may be evident. These clearly arise one within the other. The central mass may divide, and the resulting portions may divide and subdivide until an immense number of masses are produced. These may be quite separate from each other, or they may be included within the original capsule. In other cases there is no capsule, and the division and subdivision take place in a transparent, and more or less viscid substance, which lies between each resulting mass. In all cases the whole mass, and each component particle, consists of germinal matter and formed material. The latter forming a hard or soft external envelope, varying in structure, or a fluid or viscid substance external to the germinal matter, and sometimes also deposited amongst it. The power of growth of the germinal matter of man and the higher animals, like that of the lower, is, there is reason to believe, quite unlimited. Although this cannot be proved - absolutely, I shall bring forward facts which justify me in this statement. The conditions necessary for the growth of the germinal matter of the tissues of the higher animals are, however, so complicated that the vitality of the germinal matter is much more easily destroyed, and it is therefore more difficult to study the alterations produced in the elementary parts, by modification of the circumstances under which they grow; still, by a minute examination of the morbid changes occurring in tissues in disease, or induced artificially, most impor- tant general conclusions have been arrived at, and there is the greatest encouragement to continue the same course of investi- gation. Let me now show one or two specimens illustrating the character of healthy elementary parts of different ages, from the more complex tissues ; and afterwards I shall show you some which are modified by the altered condition under which they have grown. If we examine the elementary parts near the vascular 64 THE STRUCTURE AND GROWTH surface of the skin, or a mucous membrane, we shall have no difficulty in convincing ourselves of the following facts : 1. That they are much smaller than those near the surface. 2. That, although very small, the proportion of the ger- minal matter to the formed material is very much greater than in the older elementary parts. 3. That the formed material gradually increases as the elementary part grows towards maturity, the germinal matter absolutely increasing, but in proportion to the formed material it is relatively diminished. After the elementary part has reached maturity, and has advanced some distance from the vascular surface, where it commenced its existence, the outer part of the formed material perhaps shrinks and becomes harder and drier, while the germinal matter gradually undergoes conversion into new formed material, until the proportion becomes very small, and the remainder, now at a long distance from the vascular surface, and separated from any nutrient matter by a hard dry mass of formed material, as, for instance, in the cuticle, dies. No. 17 (sent round at the close of the last lecture) shows a portion of the epithelial covering of a papilla from the tongue of a girl aged ten years. This is to illustrate the growth of the epithelium. The deepest layer consists of masses of germinal matter separated from each other by a very thin layer of formed material, which is not coloured by the carmine. These are for the most part spherical or oval, some are undergoing division into two. The formed material of the deepest series is seen to be continuous with the formed material of the dermic structure. At the outer part, elementary parts are seen which occupy as much space as six or eight of the youngest ones. Each contains a dark red mass of germinal matter, larger than that of the youngest particles, but bearing a proportion to the entire elementary part considerably less than that belong- ing to the youngest particles. It is, therefore, clear that in OF HUMAN TISSUES. 65 the growth of these elementary parts the germinal matter and the formed material have both increased. The whole of the nutrient matter absorbed, has passed through the stage of germinal matter, and become formed material which has gradually accumulated. The oldest elementary parts are removed from the specimen, but the proportion of germinal matter gradually diminishes, and in the hardened scales which are about to be cast off not a trace can be shown to exist by soaking in carmine. The rapidity of division of the masses of germinal matter near the nutrient surface, and the formation of new elementary parts is especially influenced by the amount of nutrient matter present. No. 18 is a thin section of the tongue of a foetus at the seventh month. The arrangement of the muscular fibres is well seen, and the papillae are already developed as little simple elevations from the general surface. All the tissues consist principally of germinal matter, and in every part of the specimen the number of these masses coloured by carmine is remarkable. The interval between the mucous membrane and the point of insertion of the muscular fibres corresponds to the corium and submucous tissue of the adult tongue. It is occupied entirely by oval nuclei, many of which are observed to be in lines, and these can be shown to be connected with the capillary vessels and nerves. No fibrous appearance what- ever exists, and the quantity of formed material existing in connection with the germinal matter is very small. Now contrast this specimen of the tongue of a foetus at the seventh month, with No. 19, which is a corresponding section from the tongue of a child ten years of age. They are under the same magnifying power. In the first you could see eight papillse in the field at once, with the submucous tissue, and many bundles of muscular fibres. In this specimen you can only see three papillse, and a layer of submucous tissue and corium five or six times thicker than that in the foetal tongue. The 66 THE STRUCTURE AND GROWTH field is only large enough to take in just the pointed insertions of the muscular fibres, although the epithelium has been entirely removed, which greatly diminishes the thickness of the specimen. The masses of germinal matter are numerous in the simple papillae, of which the three large ones in the field are composed, but in the base of the large papillae, and through- out the corium a number of transparent spaces or areolse are observed, which are bounded by lines of small oval particles of germinal matter, the so-called nuclei of the areolar tissue. The space which looks so transparent is occupied by a tissue which possesses a fibrous appearance, which is firm and un- yielding, and which yields gelatine by boiling. The whole of this tissue is generally called connective or areolar tissue, or " bindegewebe," and those nuclei which you see bounding the transparent spaces have been christened areolar or connective tissue corpuscles. They are supposed to take part in the nutrition of this structure, which does not exist in the embryo, but which increases with age, and undergoes con- densation as life advances. In my sixth lecture I shall discuss at some length the connective tissue question, but let me now direct your attention to the fact that many of these corpuscles are connected with arteries, veins, capillaries, and nerves, and there is reason for believing that some of the more spherical particles, coloured red by the carmine, are lymph corpuscles in the lymphatic vessels, and white blood corpuscles in the capil- laries. Notice the linear arrangement of these bodies in the papillae, external to the capillary vessels, and immediately beneath the epithelium. These I shall show are undoubtedly connected with nerve fibres, and from their position, it follows that if the capillaries were congested, these corpuscles would be subjected to slight pressure. In the areolar tissue there are also a number of masses of germinal matter, which are con- verted into fat cells. OF HUMAN TISSUES. 67 LECTURE IV. Of the Increase of Elementary Parts. The effects of the conditions under which they grow being altered of Pus of Morbid Growths. MR. PRESIDENT AND GENTLEMEN, I HAVE endeavoured to show that the elementary parts of every tissue, which in many cases are termed cells, may be considered to consist, like the simplest living structures, of matter in two states, germinal matter and formed material, and that constant change is incessantly taking place in every elementary part. The matter to be animated passes into the interior, and becomes living germinal matter, while a corre- sponding portion of that already existing as germinal matter becomes formed material. In many instances, a correspond- ing proportion of this formed material is broken down and removed. Thus it is possible that an elementary part may be the seat of the most active changes, although it undergoes no alteration in its physical characters, or in its appearance, when examined by the microscope. I tried to show that, in some cases, a distinct investing membrane (cell-wall) exists, while in others E 2 68 THE STRUCTURE AND GROWTH there is no such structure. It is therefore not essential. The greatest confusion has resulted from attempts to distinguish in all cases the so-called cell-membrane from the cell- contents. In very many cases no such distinction can be made. By carmine we are enabled to decide in every instance which is the germinal matter, and which is the formed material. Neither the liver nor the kidney elementary parts, are surrounded with a mem- branous wall, and in most of the tissues of the higher animals no such structure is to be seen. I brought forward several important facts to show that even the red-blood corpuscle could not be regarded as a cell with perfectly fluid contents, through the membranous walls of which endosmose and exosmose were continually taking place. Neither the cell-theory as introduced by Schleiden and Schwann, nor any modification of it, that has been proposed, nor the view advocated by Professor Huxley, will explain many facts and appearances which are actu- ally observed. If we study the manner in which each elementary part of a tissue grows, and compare the elementary parts of .different tissues with each other, after they have been soaked in carmine, we come to the conclusion that the inner part (ger- minal matter) coloured red, is the active growing portion, and that the outer part (formed material) which is not coloured, is formed from this. The oldest part of the formed material is that which is most distant from, and the youngest part is that which is in immediate contact with, the germinal matter. The formed material exhibits the most different characters, and possesses the most different properties in different elementary parts, but in all cases its relation to the germinal matter is the same. We now pass on to consider briefly some very interesting changes, which may be shown to occur in elementary parts, when the conditions, under which growth takes place in a normal state, are modified. No. 20. This preparation shows the elementary parts situated in the middle of the cuticle of the arm, about twelve hours after the application of a blister, at the time when. the OF HUMAN TISSUES. 69 superficial layers were being separated from the deeper ones, and fluid was accumulating in the interval between them. In the part of the preparation now shown, several elementary parts are seen invested with a moderately thick layer of formed material, but to the left of the field are some having but a very thin layer indeed. Several spherical masses of germinal matter are observed in close contact with the inner surface of the softened external substance, and these are evidently in a state of active growth. They seem to be growing through the formed material. They are multiplying in number. If set free, and nutrient material continued to be abundant, they would soon increase in size, and multiply very fast. The layer of formed material, investing each, would be exceedingly thin. The masses first resulting from the growth of the germinal matter set free from the epithelial particles would be invested with a layer of formed material, and would resemble a young cell of cuticle, but as they multiplied faster and faster, there would not be time for the formation of the layer of formed material, and at last corpuscles resembling pus would result. This last stage is seen in No. 21, which was obtained from the same blister twenty-four hours after it had risen. These specimens are most important, as they show the manner in which the formed material is produced, and how, under certain altered conditions, the germinal matter may increase quickly, and a vast number of separate masses may be rapidly produced. The preparations also prove, that the thick- ness of the layer of formed material (cell-wall) is determined by the rapidity of increase of the germinal matter, which,' in great measure, depends upon the proportion of nutrient matter present. If the germinal matter of a structure grows unusually quick, particles resembling the pus corpuscle, which contains very little formed material, are produced. Conditions favour- able to the rapid increase of germinal matter are adverse to the formation of formed material. The formation of pus from 70 THE STRUCTURE AND GROWTH epithelial cells,, has been demonstrated by Virchow; but he does not seem to have observed the alteration in the proportion of the germinal matter (nucleus) to the formed material (cell- wall) alluded to. He attaches by far the greatest importance to the formation of pus in the areolar tissue corpuscles ; and con- siders that from these bodies various morbid processes which may affect other tissues, start. It seems to me, that the first stage is the more rapid multi- plication of the elementary parts, and the formation of a diminished quantity of formed material, the tendency being towards the production of similar elementary parts, but this being prevented by the abundance of nutrient material, and the rapid increase of the germinal matter. When we consider fibrous textures, I shall show you a specimen in which only soft spongy fibres are formed; and, if the process went on, the fibrous material would be less and less, until the rapidly- growing spherical masses of germinal matter were produced. There can be no doubt that germinal matter may even grow and multiply, so to say, at the expence of its own formed material. Virchow considers, that two different modes of pus forma- tion must be distinguished according as the pus proceeds from epithelium or from connective tissue. " Whether there are also forms of suppuration, proceeding from tissues of the third class, muscles, nerves, vessels, &c., is at least doubtful ; because of course the elements of connective tissue which enter into the composition of the larger vessels, the muscles, and the nerves, must be eliminated from the really muscular, nervous, and vascular (capillary) elements. With this reservation, we can for the present only maintain the possibility of two modes of pus-formation/' Neither does Virchow appear to have recognized the tendency of the germinal matter, of tissues the cornea, for instance, to form, under certain conditions, soft fibres, which are produced more rapidly than the perfectly normal structures this tendency, diminishing as the rapidity of multiplication increases, until at last pus is formed. In a OF HUMAN TISSUES. 71 preparatioo of Virchow's of the cornea in acute keratitis, in the possession of Mr. Spencer Wells, the particles of the germinal matter are seen increasing and multiplying in the same way as I described in the epithelial cells of the cuticle. They are growing at the expense of the softened formed material which surrounds them, but in adjacent parts, where the changes are occurring more slowly, the tendency to the formation of new elementary parts can be seen. As will be seen in Lecture VI, my views differ totally from those of Virchow with regard to the structure of the so-called connective tissues and the relations of the cells to the intercellular substance. Pus is not a special formation always produced from the same substance or in a particular kind of cell, but it may result from the germinal matter of any tissue, and its characters are modified to some extent, according to the circumstances to which I have already alluded. I believe that the living germinal matter of an elementary part may be set free by the destruction of the formed material, as in a scratch, perforation by the sting of an insect, or other mechanical injury, or by softening of the formed material, caused by an alteration occurring in the composition of the fluid which bathes it, or induced artificially by various chemical compounds. When germinal matter comes into contact with nutrient material under favourable circumstances its power of infinite multiplication becomes apparent. Inanimate matter near it is absorbed by the several particles, and their active powers are communicated to it. If the nutrient matter be very abundant, the particles will consist almost entirely of germinal matter ; but if not very abundant, time will be allowed for the formation of a certain amount of formed material. The germinal matter of any tissue in the body is capable of growing in this way. Every particle of germinal matter possesses the power of infinite growth. Whether a texture with a smaller quantity of formed material than in the normal tissue, and hence a soft spongy tissue, or a mass composed almost entirely of small 72 THE STRUCTURE AND GROWTH spherical masses of germinal matter (pus corpuscles) is to be produced, will depend mainly upon the quantity and character of the nutrient matter. If we look at suppuration in this light, the cause of the different characters of pus becomes evident. The germinal matter of any tissue in the body may grow infi- nitely. In the normal state it multiplies under certain restric- tions, and as it grows, the formation of formed material gradu- ally proceeds, and the germinal matter becomes separated further and further from the nutrient fluid. The formed material is prevented from undergoing any but slow change; and the removal of the small quantity of products resulting from this change is sufficiently provided for. But if the germinal matter be set free, active changes immediately commence, the inanimate nutrient matter around is soon taken up and becomes living, and the process will continue as long as the above con- ditions last. And if this were not the case, what would happen ? Why, clearly the fluids set free, prevented from undergoing the incessant change which is provided for in the normal state, would rapidly putrefy, and the products resulting from the putrefactive changes wonld soon cause the death of the tissues immediately surrounding. The process would go on, and a considerable quantity of tissue would be destroyed, and the death of the whole organism would result. In gangrene, the germinal matter is killed ; in suppuration it grows freely, and if this process did not occur, there are cases in which the death of the tissues must result. At the high temperature of the higher vertebrate animals, moist organic matter, in which the fluid is not perpetually changing, rapidly putrefies; but in the lower cold-blooded animals the putrefactive change occurs very much more slowly, and hence there is not the same necessity for the rapid conver- sion of the dead tissue into living germinal matter. In them, the process which we know as suppuration does not take place, the changes, although they are the same in their essential nature, do not go to the same extent. I have specimens of the OF HUMAN TISSUES. 73 growing elementary parts of the cuticle of the frog, after injury, which correspond exactly with those from the human skin which I have just shown you. No. 22 is a preparation of pus, several corpuscles of which are well-coloured by carmine. I have not succeeded in colour- ing all, for this structure is so delicate, and undergoes such rapid disintegration in fluid, that it is difficult to make the solution sufficiently limpid to pass easily into the interior of the corpuscle without causing its disintegration. All fresh pus corpuscles are, however, capable of being coloured . Compare this specimen with No. 23, which is a preparation showing the elementary parts of a rapidly-growing fungus, which reached the size of a small pear in a single night. It is difficult to see any membrane of formed material surrounding each mass of germinal matter. The rapid increase of such a structure is marvellous, but it cannot live long, because there is no provision for the equable distribution of nutriment to all parts, or for removing the substances resulting from the death of the particles of germinal matter. The consequence is, that the entire structure, having reached a certain size, very soon dies. The free growth of the germinal matter in such cases is very interesting ; and the readiness with which we can, by the action of colouring matters, distinguish the germinal matter from the formed material, will, I think, enable us to regard various morbid changes which appear now very complicated, from a much simpler point of view. From the examination of the above specimens, it appears that the germinal matter of elementary parts growing under certain conditions different to those existing generally, will, if pabulum be abundant, multiply very freely. A number of masses result, each of which is capable of producing new ones by division, but only a very thin layer of formed material invest- ing each will be produced, or it may not be possible to demon- strate an investing membrane at all. On the other hand, masses 74 THE STRUCTURE AND GROWTH of germinal matter which, in the normal state, multiply very rapidly, and are therefore not surrounded by formed material, may produce it, if placed under circumstances not favourable to their free increase. The white blood corpuscle, in a state of rest, and freely supplied with nutrient matter, may even form weak fibres. In coagula of fibrin, I have seen white corpuscles from the surfaces of which fibres of considerable length pro- jected, and I could see no reason for doubting that the relation of this fibrous material to the germinal matter was the same as in other structures. I have seen white blood corpuscles entangled in the coagulated transparent matter of the casts of the uriniferous tube, undergoing multiplication, and in the same case I found between the capillary loops and the mem- branous capsule of the Malpighian body, some long soft fibres, with a body in the centre exactly resembling a white blood corpuscle. White blood corpuscles had accumulated con- siderably in the capillaries in every part of the kidney in this case. In very recent lymph effused on the surface of serous mem- brane are masses of germinal matter, many of which are connected with the soft recently formed fibres. I believe that the fibres in this recent lymph consist of the formed material of the so-called corpuscles. I am still making observations on this matter, especially with reference to the question, how far a similar view may account for the formation of fibrin under ordinary circumstances. I believe that fibrin is the formed material of the white corpuscles, lymph, and chyle corpuscles. In false membranes of very recent formation, I have demon- strated the existence of numerous masses of germinal matter, in connection with the fibres, and, in the specimens which I have examined, I feel sure that the fibres consist of the formed material of these masses of germinal matter, and that they bear to the corpuscles or masses of germinal matter, the same relation as the formed material of the different tissues. The masses of germinal matter (nuclei) are as numerous as in tendon. OF HUMAN TISSUES. 75 So that germinal matter may multiply very fast, and produce less formed material than in the normal state, or germinal matter, which in the normal condition produces very little formed ma- terial may be placed under circumstances in which a considerable quantity of formed material is produced. It is therefore very essential to study the conditions which effect these very striking modifications in the germinal matter of different structures. No. 24 shows the relation existing between the germinal matter and formed material of the tendon of a kitten, and in No. 25 the germinal matter and the formed material of the true skin from a foetus, at the 7th month, are seen. The first is a structure, in which the changes are exceedingly slow ; the second is one in which we know changes are occurring constantly, and with comparative rapidity throughout life. You will admit, I think, that in all probability the germinal matter, in the one preparation, corresponds to that in the other, fibrous tissue being the result of the growth of the germinal matter of the tendon, nerves, capillaries, fibrous, elastic, and adipose tissues being formed from the particles of the germinal matter in the last specimen. The relation of the germinal matter to the formed material, in quick and slow growing tissues, is well seen in the foetus, from the 6th to the 9th month. No. 26 shows the bulbs of two or three hairs from the foot of a kitten. The bulb is much wider than the shaft of the hair. The elementary parts, in this region, are composed almost entirely of germinal matter. Higher up the formed material increases, and each elementary part undergoes condensation. Much of the water of the elementary parts is absorbed, and the whole, consequently, contracts and becomes firmer. The manner in which the formed material is produced is seen very beautifully by examining the elementary parts at different heights in a specimen of hair prepared with carmine. According to the language generally employed, the nucleus gradually diminishes while the cell increases in extent, as we ascend from 76 THE STRUCTURE AND GROWTH the deep part of the bulb, upwards towards the shaft, until, when we arrive at the dry part of the hair, the cells (cortex) are destitute of nuclei. The nature of the change is explained very simply by the view which I am advocating, and follows of necessity, because the supply of nutrient material to the ele- mentary parts gradually diminishes from below upwards. No. 27 is a thin section from a tumor which grew very rapidly. It appeared at the lower angle of the scapula of a boy, aged 12 years, and when first noticed was about the size of a bantam's egg. In six months it measured twenty-seven inches in circumference. It was firm and hard, and was intimately adherent to the scapula. The case occurred in the practice of my friend, Dr. Elin, of Hertford, to whom I am indebted for the specimen. The friends would not consent to have the mass removed, and it continued to grow for about twelve months after its first appearance, when haemorrhage occurred from some large veins on the surface of the tumor, and the boy died of exhaustion. The mass was of the same character through- out. Dr. Elin says : " It surrounded the scapula which was partly absorbed. The bone was very brittle, breaking like a piece of glass. I have no doubt that the tumor originally spread from the periosteum of the margin of the scapula." An aunt or cousin of the boy seems to have died of a similar tumor several years ago. The relation of the germinal matter to the formed material is well seen in this specimen, and the free but irregular mode of growth of the elementary parts is also well shown. No. 28 is a section of tumor, about the size of a walnut, connected with the parotid gland. The remains of some of the gland-follicles are seen, and as the elementary parts in them are dead, and are undergoing disintegration, they are not coloured by the carmine. On the other hand, the actively growing tissue contains a large amount of germinal matter, every separate mass of which is darkly coloured. The growing tissue insinuates itself in every direction, and where the parts OF HUMAN TISSUES. 77 of the growth first formed are becoming old and are losing their vital activity, offsets from the more recently developed parts, may be seen invading them. No. 29 is an interesting specimen of the so-called cancer- cells, which were passed in the urine of a patient suffering cancer of the uterus. In these morbid growths we have no difficulty in demon- strating the existence of germinal matter and formed material, and even cursory observation of the tissue affords abundant evidence of its wonderful power of rapid growth. Although it would not be possible to distinguish a single elementary part of one of these growths from an elementary part removed from certain healthy tissues, the striking irregularity of the structure, the absence of that orderly arrangement exhibited by all healthy textures, and the great extent of tissue exhibiting precisely the same characters, afford conclusive evidence as to the nature of the structures under consideration. If the elementary parts of a tissue multiply to an unusual extent, and thus overstep the limits assigned to them in the normal state, a growth is produced which may only differ from the healthy tissue with respect to its bulk, with reference to the position which it may occupy or to which it may spread, and in the relation it bears to other textures. Adipose tissue, fibrous tissue, cartilaginous and bony tissues often form tumors of considerable size in direct continuity with the normal structure. It would seem that just at the point where these outgrowths originate, the restrictions under which growth occurs normally, are to some extent removed, and here we see the power of unlimited growth, which is a property of the germinal matter of all tissues, manifesting itself. In the normal state there is reason to believe that, of the nutrient material distributed to the tissues, a certain proportion is absorbed by the germinal matter, and at length undergoes conversion into tissue, while any excess is probably taken up by lymph corpuscles, and, perhaps, by the white blood corpuscles, 78 THE STRUCTURE AND GROWTH which increase in number, and is at length restored to the blood. It is probable that, in many of the textures in the interior of the body, a balance of nutrition is thus maintained in the healthy state. If, however, the active powers of the germinal matter of the tissue be impaired, in consequence of some inherent deficiency, or through the influence of a pabulum not fitted for its nutrition, or by some change in the formed material which separates the germinal matter from the nutrient fluid, the tissue must suffer ; and, as new material is not added to it as fast as the old is removed, it must waste. In this case a large proportion of the nutrient matter will be taken up by lymph corpuscles, which will rapidly increase in number, and the pabulum, which ought to have been made into tissue, will be again restored to the blood. It seems not unreasonable to assume that a result, corre- sponding to that which is effected in the skin by the removal of the superficial layers of the cuticle and hair, and by the escape of the secretion of the sebaceous and sudoriparous glands, in mucous membranes, by the falling off of the superficial layers of epithelium, and in glandular organs by the conversion of formed material into the secretion, is brought about in tissues distant from such surfaces as the muscles, nerves, and some other textures, through the influence of little masses of active germinal matter known as the lymph and white blood cor- puscles, and thus the debris is again restored to the blood^ to be resolved into matters which may serve as pabulum, and com- pounds which must be eliminated. I must not, however, pursue this part of the question further, just now, and will only offer the suggestion that in certain cases, where an unusual growth of the tissue takes place at a particular point, it is just possible that here the arrangement, through the influence of which the tissue is maintained within its proper limits in the normal state, and prevented from extending indefinitely, is absent. OF HUMAN TISSUES. 79 LECTURE V. Of Morbid Growths. Of the Development, Growth, Nutrition, Decay, and Removal of Tissues. Of Secretion. Of the Changes occurring in Living Matter. MR. PRESIDENT AND GENTLEMEN, WHEN we were considering the changes occurring in ele- mentary parts during their growth, we saw that the proportion of the germinal matter to the formed material altered as the elementary parts increased in size. At first each consists of a mass of germinal matter, which is separated from its neighbours by a very thin layer of soft formed material. At this period of its life it may divide and subdivide, and several separate masses may be produced. Gradually, however, as each elementary part recedes from the vascular surface, the germinal matter ceases to divide and subdivide, although it still absorbs nutrient material and grows. Inanimate matter becomes germinal matter, and germinal matter becomes formed material. At last, when the elementary parts are separated by a considerable stratum of younger ones from the nutrient surface, the formed material becomes harder and drier, and less permeable to mois- ture. The changes taking place in the germinal matter, now imprisoned in a firm thick layer of formed material, occur 80 THE STRUCTURE AND GROWTH more slowly. It still lives, and slowly diminishes as its outer portions become converted into formed material. At last the conditions, under which it is placed, become so altered, that it dies, and perhaps becomes liquefied. A small space remains and marks its original situation. The rate of multiplication of the masses of germinal matter seems to depend principally upon the quantity of nutrient material in contact with them. If this be very abundant they multiply very rapidly ; while, if it be scanty, they increase in number very slowly. Rapid multiplication of the masses of germinal matter is constantly associated with the presence of a large amount of nutrient matter, and the production of a very small proportion of formed material. Elementary parts which, in the normal state, become sur- rounded with a moderate thickness of formed material, may multiply very rapidly under conditions which render the pro- duction of formed material impossible. Thus the young elementary parts (cells) of cuticle may grow more quickly than usual, and at last masses of germinal matter, destitute of formed material, growing and multiplying rapidly, may be produced. Pus corpuscles are thus formed ; but before absolute pus is produced, there is always manifested a tendency to the development of such elementary parts as are met with in the normal state. I have referred to the orderly arrangement which the elementary parts of all healthy tissues at every period of exist- ence exhibit, and have shown that in certain morbid growths no such order exists, that in healthy organs there is a provision which prevents the different tissues, of which they are composed, from overstepping the limits which are assigned to them, while, in morbid growths, no such restrictions exist, and the power of infinite growth, which the germinal matter possesses, becomes apparent. The difficulty of discussing many of these important ques- tions is much increased by the very guarded manner in which OP HUMAN TISSUES. 81 writers are in the habit of expressing themselves. The obscure language often made use of, and the complicated words, the definition of which is continually changing, not unfrequently render it a matter of great labour to the reader to form any accurate idea of the exact opinion which the author holds. In endeavouring to avoid these objections, by expressing myself simply, and without making use of the terms generally employed, I am well aware that my views will be fully exposed to the attacks of opponents, and any errors not being screened by ambiguity of expression, will be at once discovered; while I may also be open to the charge of being presumptuous, and shall thus, when in error, necessarily incur double censure. Still, by pursuing this course, it is obvious that free discussion will be much facilitated, and the truth will, in all probability, sooner be discovered. To this everything should be made to give way, and personal interests must be absorbed in the general advantages which must result from efforts to facilitate the progress and diffusion of scientific truth. An abnormal or morbid growth may originate in any tissue in the body. If it commences in a tissue of simple formation, it will retain, to a great extent, the character of this structure, but if it arise in one of the higher tissues it will soon become so modified that it would not be possible to determine its origin from its microscopical characters. The character of a morbid growth will, therefore, in great measure, depend upon the tissue in which it originated. Not unfrequently it would be quite impossible to distinguish a section of a morbid growth from one of the healthy tissue in which it commenced. In other cases an important modification in the elementary parts will have taken place. The muscular fibre cells around the pylorus, and in other parts of the intestinal canal, sometimes increase enormously in number, leading to the formation of a firm unyielding tissue, which is almost as firm as fibro-cartilage (sometimes described as scirrhus of the pylorus). As the contractile element increases, it loses its p 82 THE STRUCTURE AND GROWTH contractile power, and the whole mass appears to be composed of a form of fibrous tissue, in which the separate fibres are very distinct, and arranged parallel to each other in concentric layers. I shall be able to show you a specimen of a healthy structure in which the contractile elementary parts of organic muscle are seen, at the margin of the bundles, to sluvdo into those of fibrous tissue. Up to a certain period the germinal matter of these might have produced organic muscle, but the contractile tissue not being produced, a lower form of tissue is as it were formed in its stead. Since such a transition may be demonstrated in the healthy state, we shall not be surprised at finding what amounts to a very exaggerated change, in disease. The ele- mentary parts have multiplied enormously, but they have developed, not their characteristic contractile tissue, but a lower and simpler form of formed material, not possessing the peculiar endowments of the normal structure. If the restrictions, under which a soft healthy tissue grows, be removed, a soft and often very rapidly growing structure results. Those structures which in the healthy organism grow fastest, and pass most rapidly through the various stages of their existence, as would be supposed, give rise to the formation of the most terrible and uncontrollable of morbid growths. An irregular growth of a part of the secreting structure with the vessels, for instance, of the liver, kidney, mamma, sweat glands, &c., may lead to the formation of a very soft, spongy, and highly vascular growth, which will attain a very large size, and appropriate the nutrient material which properly belongs to other textures. After a time, perhaps, it reaches the surface of the body, and fatal haemorrhage may take place from its super- ficial vessels. In many such morbid growths we can distinguish the elementary parts which have descended from those taking part in secretion, although they have become much modified, from the elementary parts which are connected with the vessels OF HUMAN TISSUES. 83 prolonged into the structure. The former constitute the ' cells/ or ' cellular elements' of the morbid growth, and the latter with the vessels themselves, form the ' matrix/ or walls of the areolse or spaces in which the cells lie. When we consider what a very slight derangement of the elementary parts at an early period of development would infallibly lead to the suppression or exaggeration of normal structures, which are their direct lineal descendants, is it not wonderful that morbid growths (irregular growth of one or more tissues) or monstrosities (exaggeration or suppression of series of elementary parts from which numerous different tissues, entire organs, or limbs, are produced) are not of yet more frequent occurrence than they are ? Many healthy structures may be removed from the part of the body where they have been developed, to a distant part, and will nevertheless grow there. Skin, hair, teeth, and other tissues have been successfully transplanted, but perhaps the most interesting, and not the least useful, instance of this kind which could be adduced, is the transplantation of growing bone. M. Oilier has removed a portion of the periosteum from a bone, and planted it in a distant part of the body, under the skin for instance, and bony tissue has been produced. The periosteum contains bone germs, which only require nutrient material to undergo development into ordinary bone. The practical surgeon will, of course, soon apply so important a discovery to the treatment of certain cases. Some textures retain their vitality after they have been separated from the parts where they grew, for a much longer period of time, and have a much greater power of resisting destructive agencies, than others. In some of the lower animals, so active is the tendency to growth, and so strong the power of resisting what would seem to be adverse conditions, that mechanical separation into numerous parts serves but to increase the rapidity of the production of separate independent organisms. F 2 84 THE STRUCTURE AND GROWTH When we consider how very greatly the normal tissues of the higher animals vary in structure, properties, and power, we shall not feel surprised at the great differences observed in the morbid growths which originate in them. Some of these grow very slowly, others very rapidly some form circumscribed and comparatively isolated masses, while others burrow in every direction, invading every tissue in their immediate neighbour- hood, and growing at its expense. A part of a morbid growth may be cut off from nutrient material by the growth of the rest, and may die. Into this dying or dead portion, part of the living mass may grow, and, as it were, live upon the very tissue which once formed a living part of the whole, and of which, in fact, the last is a direct extension. The larger the growth becomes the greater seems to be its powers of resistance, and the more readily do the normal struc- tures yield to its advance. The least particle of it will spread rapidly, its increase appearing to be limited only by the supply of nutrient material. The faster it grows the more irresistible the power of growth seems to become, and, especially in cases where the growth is composed of a number of loosely connected portions, even a very small piece detached and carried to a distant part will readily grow. In not a few cases a very minute portion of the germinal matter of one of these struc- tures may be carried away to a distant part of the body, and so powerful is its tendency to animate any form of nutrient matter in the organism, so unrestricted the conditions under which it grows, and so increased is its power of resisting the action of conditions which would doubtless have destroyed the germinal matter from which it originally sprung, that it will grow wherever it may chance to become stationary. An elementary part or even a little of the germinal matter may be detached from the original mass, and removed to distant parts by the movement of organs one on the other, or it may be carried a long way from the point where it originated, by the lymphatic vessels, and, there can be little doubt, by the blood vessels also. OF HUMAN TISSUES. 85 These morbid structures may ultimately be found growing in connection with healthy tissues with which they have no characters in common. A bone-germ, detached from a soft, rapidly-growing, spongy, bony tumor, may take root even in the pulmonary tissue, and thus several hard solid separate masses of bony structure, which may attain considerable size, may grow in different parts of the lung. In all these cases the vessels grow with the other elements of the tissue, and thus the conditions for unlimited increase without order, in an irregular manner, and without advantage to the organism, are present, and may persist. These results appear to depend more upon the circumstance that the restrictions under which the growth of the tissue occurs normally, are removed, than upon any special peculiarities of the morbid growth itself. The conditions favourable to the development of such structures are not the result of accident, but depend upon changes which have occurred at an earlier period of time, and these may, in the same manner, be referred back. The hereditary nature of many of these growths, and the symmetrical character of certain morbid processes, receive something like an explanation from the view I have taken up, but into these subjects I must not now enter. The structure of the elementary parts from a malignant growth is represented in Plate IV. I have endeavoured thus to indicate very briefly some of the circumstances which probably determine the different charac- ters of various morbid growths, including those tumors which have received the very inappropriate term of benignant, and the numerous intervening forms which may be said pass by almost insensible gradations into those of a malignant character. I might have advantageously devoted a longer time to this important subject, but I am compelled to dismiss it with these very few general and superficial remarks; I hope, however, you will bear in mind that the observations I offer are only intended as an explanation to the preparations which I show you ; and, therefore, I think I may venture to make 86 THE STRUCTURE AND GROWTH many cursory remarks which otherwise would hardly be justifiable. Let us now examine one or two specimens of vegetable tissues, in order to ascertain if their structure and growth can be explained by the same general doctrine which I have shown will account for the appearances observed in the tissues of the higher animals, both in a state of health as well as in disease. I commenced with the description of the characters of mildew, one of the simplest structures in the vegetable kingdom, and I have also shown you a preparation of another fungus. In these, as in the animal tissues, the germinal matter was coloured red with carmine, and the formed material remained perfectly colourless. It is, however, desirable to examine the tissues of one of the higher plants. No. 30 is a portion of the young leaf of the common mig- nionette, showing the germinal matter coloured red with carmine. No. 31 is a portion of the epidermis from the same plant. Numerous stomata are visible, and in the youngest elementary parts, masses of germinal matter, stained with the carmine, may still be observed. No. 32 is a small piece of a rootlet of the mignionette. The elementary parts in this specimen are very beautifully coloured. No. 33 is a section of a common potatoe near the point at which a bud is being developed. In many of the elementary parts, the primordical utricle and the nucleus (germinal matter) , are well coloured, and in many cases, the central part of the germinal matter, is occupied by numerous small starch grains. I propose to call the matter deposited amongst the particles, or in the central part of the germinal matter, secondary deposits. The germinal matter will always be found between these and the so-called cell- wall. It is possible that these substances are precipitated in consequence of certain changes having occurred in the formed material in the interior, of a different nature to those which led to the formation of the envelope or cell-wall OP HUMAN TISSUES. 87 on the external part of the mass. In many cases the secondary deposits accumulate as long as any germinal matter remains in a living state. (Plate III, Figs. 19, 22, 12, 3.) I have examined several vegetable structures, and they all exhibit the same general characters, and become coloured by carmine in the same manner. We may then, I think, conclude that the elementary parts of all tissues, vegetable as well as animal, are composed of matter in two states, germinal matter and formed material, and that all growth takes place through the intervention of the germinal matter alone, which possesses the power of growing infinitely. It appears that in certain cases both in animals and in vegetables the formed material or insoluble substances resulting from certain changes effected in it, may be deposited upon the external surface of the germinal matter, or may accumulate amongst the particles of the germinal matter itself. The deposit in the latter case would take place first of all in the fluid which intervenes between the spherical particles of germi- nal matter, and this process having once commenced might proceed until a very considerable accumulation had taken place. In many structures, the substance which is precipitated amongst the living particles in an insoluble form, is prevented from escaping through the outer layer of formed material or membraneous capsule (cell-wall) within which the germinal matter (primordial utricle) and the substances which I have spoken of as secondary deposits (a part of the so-called cell contents) are found. The escape of these substances, which are precipitated in an insoluble form, can never take place without the destruction of the whole mass, or the formation of an opening. If the products so formed were fluid, they would coalesce, and at length a mass of considerable size might be produced, and the actively growing or germinal matter would form a laver between the insoluble substance and the inner 88 THE STRUCTURE AND GROWTH surface of the wall of the capsule, the position which the primordial utricle occupies in the vegetable cell, and the germinal matter (here called the nucleus), in the fat-vesicle. When these changes commence in the fat-cells, a little oil- globule is sometimes seen in the centre of a mass of germinal matter, and this might be mistaken for a nucleolus, but it is not coloured by carmine ; and by carefully examining several masses in different stages of growth, its true nature can be made out. In other cases the fatty matter is deposited on one side of the germinal matter which gradually becomes pushed, to the opposite part. In both cases the relation of the germi- nal matter to the investing membrane and the secondary deposits is precisely the same. (Plate III, Figs. 17, 19, 22.) Sometimes particles in all parts of the germinal matter rapidly grow, pass through their stages of existence, and become resolved into a substance allied to that which is ordi- narily applied to the thickening of the outer membrane. In this case the germinal matter will be found partly just within the membrane, and partly amongst the insoluble particles in the interior. In the large starch-holding cells of the potatoe, the living germinal matter is seen to be in contact with the inner surface of the capsule, while the starch-granules accumulate for the most part in the centre. There is no difficulty in finding starch-granules, in every stage of formation; and careful examination will, I think, lead the observer to agree with me in the opinion, that the starchy material is deposited in successive layers, so that the inmost are the first, and the outermost, the last layers which have been formed, and the deposition has taken place more rapidly at one part than another, as shown by the different thickness of the layers at different parts of their circumference. (Plate III, Figs. 19, 2) The following very interesting point will also be observed by careful examination : Insoluble matter has been deposited in successive layers on the inner surface of some of the large OF HUMAN TISSUES, 89 capsules, producing a laminated appearance exactly resembling that of a starch-granule, but spread out, as it were, over an extended surface. It is also important to observe that, at short intervals, there are openings in these transparent lamellae through which nutrient material passed into the interior of the capsule. These, are more correctly described as spaces or channels, which probably are closed on their outer surface by the thin membrane of the original cell- wall. Here the depo- sition of insoluble matter has never taken place, and through the spaces, currents of fluid pass to the interior, and continue as long as any living matter exists within in an active state. The mode of deposition of this insoluble matter can be very satisfactorily watched in these capsules (Plate III, Figs. 20, 21.)* In many other vegetable starch-holding cells, the lamellae and pores above described may be seen. According to this view, the starch-granule is formed on the same principle as a calculus, and the deposition of the starchy matter from solution is purely physical, but its formation depends upon the peculiar properties of the particles of germinal matter, which select and combine substances in a special manner while passing through the various stages of their existence. At last their active powers cease, and their constituents become resolved into starch amongst other sub- stances.f One of the most interesting points which has been demon- strated during the last few years, in connection with the chemical changes occurring in animals, is the discovery that * The insoluble lamellae are not starch, although they refract and polarise like this substance. These peculiar cells contain very little starch, and there can be no doubt that the changes which usually lead to the formation of starch have in these instances been modified so as to cause the altered matter to be deposited in a different position. t The opinions generally held on the formation of the starch -granule are different to the conclusions in the text, vide a Paper by Mr. Busk, in Vol. I., New Series of the Trans, of the Microscopical Society, 1853, p. 53, and Professor Allman, " On the Probable Structure of the Starch-Granule." Quarterly Journal of Microscopical Science, Vol. II., p. 163. 90 THE STRUCT UKE AND GROWTH matters nearly allied to starcli and cellulose were formed in them, as well as in plants. C. Schmidt, in the year 1845, proved the existence of a substance of the cellulose series in certain Ascidians ; and Virchow, about the year 1854, made the very important discovery of an amyloid substance in the human subject. This was found in the form of roundish bodies in the deep layers of the membrane lining the cerebral ventricles, and that which lines the canal of the spinal cord. Since this time, amyloid matter has been demonstrated in many other situa- tions. In the liver it is found in considerable quantity, and, as Dr. Pavy has shown, is a substance which is so easily and rapidly converted into sugar after death, that Bernard was led to conclude that sugar was actually formed in the liver in con- siderable quantity in health. In certain cases of disease, a substance containing amyloid matter accumulates to an enormous extent in the lobules of the liver, especially in their central part, giving rise to the amyloid or waxy degeneration (scrofulous liver, albuminous liver, spek-krankheit) . This amyloid substance is one of several compounds, into which the formed material of the liver elementary part is resolved. In health it is carried away in a soluble form, and probably is soon converted into other compounds, which are at last resolved into carbonic acid. In diabetes, it is converted into sugar, and in certain scrofulous cases it accumulates in the liver, and in other tissues of the body, in an insoluble form. It is probable, how- ever, that this amyloid material is not alone produced in the liver, for in disease it is found in connection with almost all the tissues, especially in the coats of the arteries. Busk and Bonders stated that the so-called amyloid bodies in the brain, and other parts of the nervous system, were actually composed of starch. Mr. Busk described their con- centric laminae, and stated that they behaved towards polarized light, and iodine, just as starch does. Of late, however, doubt has been thrown upon many of these statements, by the detection of starcli almost everywhere, and it has been hinted, OF HUMAN TISSUES. 91 or actually asserted, that in many cases in which starch had been detected, it had an extraneous origin. Unquestionably there are cases in which this mistake has been made. Several have come under my own observation, but I feel sure that Busk and Donders were quite alive to the possibility of such an origin of the starch, and Virchow has especially cautioned observers against mistaking starch and cellulose accidentally present, for the substances actually formed in the living animal tissue. I have always studied the fallacies likely to mislead in the course of microscopical inquiries with the greatest interest, and although I have always felt quite sure of the accuracy of the observations referred to above, it was not possible, without the most positive demonstrative evidence, to oppose the negative statements of those who were unable to confirm the reactions which others had obtained. It is a pity that any one should record negative results in an examination like the present, especially where, as is well known, there is some difficulty in obtaining a uniform action from the test, unless he has devoted considerable time to all the little niceties which experience proves to be necessary in employing chemical tests in minute investigations. Within the last few days, I have received a specimen of a can- cerous liver, which weighed upwards of 13 Ibs., containing nume- rous bodies exactly resembling starch-granules. The evidence here against the accidental presence of starch is most positive. 1. From the testimony of Dr. Webb, of Wicksworth, from whom I received the specimen. 2. From the fact that these bodies were found in sections cut from the very centre of the mass I received. 3. That the starch bodies may be seen in the specimens actually embedded in the tissue, and they may be removed with fragments of the tissue of the liver adherent to them. The specimens have been preserved, and I have every reason to believe will keep for years. As to the facts, therefore, in this one case, I can speak most confidently. 92 THE STRUCTURE AND GROWTH In No. 330, a great number of these bodies, which I must call starch granules, for it would be difficult to distinguish many of them from potatoe starch, are present. You see them embedded in the substance of the tissue at different depths. The remains of the cell containing network and of the con- tained liver elementary parts (cells), can, in some situations, be distinctly made out ; and in some specimens, the starch-granules were lying in immediate contact with the wasted cells, as if they were produced by changes occurring in the matter of which the elementary parts were once composed. Some of those which appear quite upon the surface cannot be moved by pressing the thin glass cover with a needle, proving that they are adherent to the tissue. I can show you the depressions in the tissue, which were occupied by others which have been removed. Some have very sharp angles, and most are discoidal in form. There is an indication of the existence of the laminae ; but in the faintness of the lines, and by the sharp angles seen in many, they differ from ordinary potatoe-starch. In No. 336, a section from the same liver, which has been treated with iodine and sulphuric acid, is shown. The globules are of a dark blue colour, and they are so highly coloured, that they appear quite black, when examined by transmitted light. Although the concentric lines are not so distinct as in starch, I believe that, as in the starch-granule, the starchy matter has been added in successive layers just as the calcareous matter is deposited round the spherical particles of brain sand, or calcu- lous matter around smaller calculi, or around any foreign body which may serve as a nucleus for the deposition of calculous matter. Under certain circumstances then, it appears that the formed material produced by germinal matter, both in vege- tables and animals, may become resolved into starchy and other substances. The starchy matter may be deposited around granules, layer after layer, until a mass of considerable size is produced ; or a material allied to starch, and formed from the OF HUMAN TISSUES. 93 same germinal matter as this substance may be deposited upon the inner surface of the investing membrane (cell-wall) of an elementary part in thin laminae. There is every reason to believe that in this case of cancer of the liver, the cell containing network of the lobules had been encroached upon by the cancerous growth, growing prin- cipally in the interlobular fissures. The excreting channels which carry off the bile would soon become occluded, and the distribution of blood to the substance of the lobule much diminished. Nevertheless, some of the masses of germinal matter of the original elementary parts still retained their vitality, as was proved by their being coloured by the carmine, and a certain amount of formed material under these disad- vantageous circumstances was produced. We may assume that this, being placed under very adverse conditions, did not undergo precisely the same changes which occur in the normal state ; and amongst other substances resulting from the changes induced was this starchy matter, which was prevented from escaping, and was slowly deposited in the insoluble form, the amyloid masses gradually increasing in size by deposition on their exterior. I propose now to consider briefly the bearing of the views I have brought forward upon the development of tissues, and their nutrition, growth, and decay. We shall next see how far they are applicable to the process of secretion; and lastly, I shall endeavour to draw some general conclusions as to the nature of the changes occurring in living matter, and try to ascertain what objects are fulfilled by the relation of the formed material to the germinal matter which seems to be so constant in the most dissimilar tissues. In my second lecture, I endeavoured to show what was meant by certain degrees of vital activity. Life slowly shades into death, and although there is no difficulty in distinguishing a living structure from a dead one, there are in the normal state of living structures certain particles which possess some of 94 THE STRUCTURE AND GROWTH the properties of germinal matter, although they are not capable of animating lifeless particles. These particles are in a transi- tion state, and the matter of which they are composed is just about to become formed material. They are passing from a state of great activity to a less active condition. The oldest formed material is, as a general rule, gradually oxidised, and converted into simpler substances, which pass into the blood, and undergo numerous changes. When the germinal matter of a tissue has almost entirely undergone conversion into formed material, and is, therefore, separated a considerable distance from the nutrient matter, the tissue possesses very little power of resistance, and in many cases is absorbed and replaced by new tissues. In many cases, as I have before stated, the remains of the germinal matter enclosed in a thick layer of formed material, and separated a considerable distance from the nutrient matter, dies. The currents of fluid through the formed material, therefore, cease, and this substance is no longer permeated by fresh particles of fluid, by which process alone its integrity, and its functional activity, can be maintained. The tissue is dead, and will soon undergo decomposition, unless it is re- moved by living germinal matter, growing at its expense. If decomposition ensues, and the escape of the products is not provided for by other means, the tissues adjacent become softened and destroyed, and thus an outlet is made. As a general rule, however, before the remaining germinal matter dies, the formed material becomes altered, and the tissue is removed by the encroachment of living germinal matter, which appropriates it, and thus it may again be built up into tissue. There are few questions of greater interest than those which bear upon the removal and reconstruction of tissue in the adult. Until we have a history of these processes, it will be impossible for us to obtain a clear insight into the nature of morbid changes. I have tried hard to ascertain if the dying tissue is OF HUMAN TISSUES. 95 encroached upon by the living elementary parts in the neigh- bourhood, or is, so to say, removed by the increase of the small amount of germinal matter still remaining encased in the thick layers of formed material. I believe that both processes occur. In developing bone I have seen appearances which make me think that an alteration and softening occur in the calcined formed material, within which a small portion of living germinal matter yet remains, and that these masses of germinal matter thus coming into contact with matter which they can appropriate, increase at the expense of this old formed material. After it has all undergone conversion into germinal matter or has been absorbed, the production of formed material again commences, so that the germinal matter may, at one time, produce formed material, and under other circumstances increase at the expense of the very tissue it has produced. The germinal matter of the lacunae of fully formed bone, undoubtedly dies, and then the bony tissue is removed by the growth of germs which lie outside the capillary vessels. It is most difficult to ascertain the precise manner in which these processes of building up and destruction are effected, for the investigation requires the tissues to be so prepared, that the thinnest possible sections of textures which have not been altered by drying or heating may be examined by the highest magnifying powers. It is nevertheless quite certain that this alternate formation and removal actually occurs in bone. The existence of the processes has been demonstrated by the beautiful researches of Tomes and De Morgan, published in the Phil. Trans., in 1853. There can be no doubt that a similar process takes place in the other tissues of the body, which are at a distance from cutaneous and mucous surfaces, and in the gland structures themselves, although the precise order in which the change occurs has not been so clearly demonstrated. The epithelium of these organs is removed, and replaced as I have already described, but, besides this, the elementary organs of which 96 THE STRUCTURE AND GROWTH the gland structure is composed are removed. The oldest obules on the surface of the liver, are undergoing absorption and removal, and a similar process is taking place beneath the capsule of the kidney. The growth of the germinal matter, the formation of formed material, and the continual disintegra- tion of this, are taking place in all tissues, but the changes occur much more rapidly in some textures than in others. The perpetual alterations which take place in the elemen- tary parts of the younger structures in course of development, and which lead only to the formation of imperfect tissues of temporary use, are instrumental in bringing about the condi- tions under which alone the higher and more perfect structures can be found. In the development of all the higher tissues, structures which serve only a temporary purpose, precede the formation of organs which are to retain their characters for the remainder of life. In many cases tissues having, nevertheless, performed very important offices for a time, cease to fulfil the requirements of the organism. They waste, and are removed to make room for more perfect structures, or they may have no permanent representatives. These temporary structures are not entirely removed by absorption, and a slight residue remains, which, in some cases, serves as a sort of matrix for the development of the new structure ; or this residual tissue may form, as it were, lines by which the new structure undergoing development is conducted to distant parts. When we examine fully developed tissues, we generally find a certain proportion of indeterminate structure, for the presence of which it is often very difficult to account ; and its true nature and relations can only be under- stood if the same texture in the same species of animal be carefully examined, in precisely the same manner, at different periods of life. From what I have said of the power of infinite growth of germinal matter, it is almost needless to state that in all tissues OP HUMAN TISSUES. 97 there is provision for the development of a greater number of elementary parts if they should be required. Indeed, in the intervals between adjacent but dissimilar textures, there are elementary parts which are but imperfectly developed. Up to a certain period, these might have been converted into perfect structures, but this being passed, they remain in a sort of degraded condition, and are not functionally active. They produce a low form of tissue. The germinal matter of the elementary parts outside a bundle of striped or unstriped mus- cular fibres, nerve fibres, and some other tissues, instead of producing the peculiar formed material characteristic of these tissues, which possesses special endowments, only give rise to the production of a structure closely allied to fibrous tissue. As will be supposed, a low form of fibrous tissue is found in connection with all the more complicated tissues of the higher animals. We shall again refer to this subject, in connection with the subject of areolar tissue. When several elementary parts have been formed by division, and thus the basis of the structure laid down, this process of divi- sio nceases in that part which was first formed, and the production of formed material commences. Each mass of germinal matter absorbs nutrient material, and gradually the formed material increases, always being deposited between the portion last formed and the germinal matter. Thus each mass of germinal matter 7 is gradually separated farther and farther from its neighbours, by the increase of the formed material. In certain cases the whole tissue is made to expand equally, in all directions, so that we may have a continually increasing solid figure, growing equally, and preserving the same characters in every part. The multiplication of elementary parts still proceeds in certain parts of the tissue, at least for a time. In a leaf the process soon stops, and the leaf, having attained a certain size, does not increase, and at certain periods all the elementary parts are cut off from the supply of nutrient matter and die. G 98 THE STRUCTURE AND GROWTH The entire leaf, or stem with its leaves, drops off, or the entire plant dies. In animal tissues, however, the arrangement is such that elementary parts, instead of dying and being cast off in quan- tities at one time, are very gradually removed. New ones are continually growing up to take the place of those which have lived their life. The division and subdivision of germinal matter, and the multiplication of elementary parts, goes on throughout life, very rapidly in some tissues, very slowly in others ; but, even in very advanced age, it may occur in all. In the rapidly changing structures, especially in the glands, the con- stant activity of which organs is necessary to life, there must always be a certain number of elementary organs, and ele- mentary parts, which, so to say, have only just commenced their existence. At this time derangements may take place in their growth, owing to improper pabulum and other circum- stances. The effects of these alterations may not be made manifest till long after they have occurred, in fact, not until the time comes when they should take the place of their pre- decessors, which in some cases does not occur until after the lapse of years. Such changes, however, affecting important glands, like the kidney and liver, and depending on causes long since forgotten, after progressing slowly, and almost impercep- tibly are at last, fatal. By making out the history of these alterations, and study- ing the conditions under which they occur, we may hope to be able to lay down such rules as may prevent or retard their progress ; or, by demonstrating that certain results must neces- sarily follow certain courses of action, we shall be justified in strongly insisting on the importance of rules of conduct being carried out, which may much reduce the probability of their occurrence. I believe that in the development of tissue, the germs, which by their growth are instrumental in the production of the perma- nent texture, existed as new centres in that portion of the germi- OF HUMAN TISSUES. 99 nal matter of the pre-existing elementary parts which was not converted into tissue. It seems to me then, that in certain cases, a mass of germinal matter may in great part undergo conversion into formed material ; but in the small portion which remains, new centres of growth are produced. The germinal matter, of which these are composed, may not assume a state of activity, perhaps, for a long period of time. When the period for their development has arrived, the formed material around is softened. They grow at its expense, and at length the old tissue is removed and a new one produced, differing from it in most im- portant characters. Successive series of new centres arise from those pre-existing, and these last were developed from prior ones. In growth, the elementary parts multiply in number, and they may also increase in size. In nutrition, without growth, an amount of inanimate matter becomes living germinal matter within a given time, exactly corresponding to the proportion of germinal matter which under- goes conversion into formed material, and this makes up exactly for the quantity of old formed material, which being no longer fit for work, is disintegrated, converted into soluble substances and removed. In the higher animals, and in man, I believe the constituents of the food, proper for the nutrition of the tissues, become living germinal matter in the epithelium of the intestine, and in the chyle corpuscles. These living particles, pass through their definite stages of existence. The chyle corpuscles give rise to the formation of red-blood corpuscles, the formed material, of which becomes resolved into substances differing in composi- tion and properties from the food, as albumen and other sub- stances which are dissolved in the fluid part of the blood. These constituents of the serum of the blood are not living, they have been so, and may again become so when taken up by the germinal matter of the different tissues. I have already adverted to the position in which lymphatic vessels are found. Within them are masses of germinal matter G 2 100 THE STRUCTURE AND GROWTH which, doubtless, would appropriate any redundancy of nutrient matter which the neighbouring tissues could not take up. In the form of lymph corpuscles this is returned to the blood, and these bodies at length assume the form of white blood cor- puscles, as already stated. It is not improbable that the hsemato-crystallin of the red-blood corpuscle is by the action of oxygen gradually resolved into two sets of compounds, the one which takes part in nourishing the tissues (albumen and other substances), the other which is to be eliminated (urea, extractives, carbonic acid, and other substances). If all these processes go on actively, the entire organism is in a healthy condition, but, if any be imperfectly performed, the action of the tissues is affected, and disease may result. In secretion, the formed material is, I believe, gradually altered, and is at last resolved into the substances charac- teristic of the secretion. This process is much more rapidly effected in some secreting organs than in others. The end of the life of the particles of germinal matter of the elementary parts of the liver, is the production of formed material, which is at length resolved into bile, a substance easily converted into sugar, and other compounds. As urea exists in the healthy blood, it may be that it is only separated and taken up by the elementary parts in solution in water. Lt is most likely, how- ever, that the extractive matters, and some other constituents of the urine, and perhaps part of the urea, result from changes taking place in the formed material of the renal epithelium. The peculiarity of each secretion depends to some extent upon the state of the blood, but mainly upon the peculiar powers of the germinal matter, and these properties often differ in the most remarkable degree in animals closely allied to each other. The milk, for instance, of mammalian animals possesses certain characters which at once distinguish it from every other secretion. It contains, as is well known, a cheesv substance, a fatty and a saccharine substance, and saline matters, but these differ in their relative proportions and in some important OF HUMAN TISSUES. 101 qualities, in the milk of different animals. These differences depend upon the properties of the particles of germinal matter of the lacteal elementary parts which at length become resolved into the constituents of milk. As we have (so to say) certain generic and specific differences in the tissues of various animals, so also corresponding differences exist as to the chemical com- ponents of their bodies. We have in all, bile and saliva and gastric juice, and urine, &c. ; and in the blood we have albumen and fibrin and haematoglobulin. But the bile, saliva, and other secretions of different animals, possess well-marked differences, and of albumen and hsematoglobulin there are certainly many different kinds capable of being distinguished from each other by chemical and other tests. It is probable that we can, as yet, form but a very imperfect idea of the chemical changes which take place in, and the number of compounds which inter- vene between, a particle of food and the particle of tissue formed from it. These chemical substances may vary very slightly in composition and other characters, in animals nearly allied to each other, so that many varieties may be produced, all differing slightly from each other, but having certain characters in common which justify us in calling them all by one name. The substances resulting from the disintegration of these compounds are in many cases exactly alike. Urea and uric acid are formed by animals whose albumen and hoematoglobulin are very different. We find constantly that the most complex substances, when acted on by oxidising agents, give rise to the production of precisely the same compound. The elements of the substances are probably grouped together to form these complex compounds after the conversion of the pabulum into germinal matter, while the particles of germinal matter are passing through the various stages of their existence. At present we cannot form any idea of the nature of the chemical relations of the living matter. As the particles pass through the stages of formed material, disintegrated formed material, and products resulting from the action of oxygen on these, they 102 THE STRUCTURE AND GROWTH become more and more simple in constitution, until, perhaps at last, they are resolved into carbonic acid, ammonia, and other comparatively simple substances. The consideration of the different results of the growth of the germinal matter is interesting in another point of view, which I may just hastily glance at. Although in different animals of the same species, the powers of the germinal matter, the pro- perties of the tissues formed from it, and the chemical com- pounds produced in the organism, exhibit certain differences, these differences shade into insignificance when compared with the differences observed with respect to the same points in animals of different species. It seems probable that in certain cases in which it is difficult to determine the question of distinct species or mere variety, a careful study of the physiology of the creature would much assist in settling the question. Anything approaching a complete history of the life of a creature would, in all probability, enable us to determine at once the question of species or variety. Secretion then differs from the formation of tissue only in this, that while the end of the existence of the particle of germinal matter of a secreting elementary part is the pro- duction of formed material, which is soon resolved into the constituents of the secretion, that of the tissue forming particle, is the production of formed material, which shall last for a much longer time, and in many tissues perform, while it lasts, very important offices. But even this tissue is gradually resolved into simpler substances, and, moreover, gives place to new tissue which is being produced by the germinal matter. Let me contrast with each other, in few words, the pro- cesses of development, growth, nutrition, and secretion. In development one series of elementary parts is replaced by another, having different endowments, and the last has descended from the first. In growth, an increased number of elementary parts is produced. In nutrition, the decay and removal of old elementary parts is exactly compensated for by the growth of OF HUMAN TISSUES. 103 new ones. The old elementary parts are removed entire, in some tissues (mucous membranes, cuticle, &c.), while in others they are appropriated by living germinal matter, and absorbed (nerves, muscles, &c.). In secretion the formed material of the elementary part is soon resolved into the substances of which the secretion is composed. I have endeavoured to show, with regard to the elementary parts, ordinarily termed cells, that a cell wall is not a necessary structure, and that the action of the cell, which has long been a subject of very warm discussion, consists simply in this, that the living particles of the germinal matter pass through certain definite stages of existence. During the active period of the existence of these living particles, the most important chemical changes are occurring, and every particle is moving in a deter- minate direction from a centre. At last it becomes resolved into formed material, the composition and properties of which are very different, and these differences depend upon the different powers of the germinal matter which produced it. The conversion of germinal matter into formed material goes on, and the germinal matter of many tissues lives for a short time after the death of an animal ; but sudden death by lightning, or violent shock, &c., may, there is reason to believe, at once arrest the conversion of germinal matter into formed material. Let us consider very briefly what very important objects, especially in the tissues of the higher animals, are fulfilled by these wonderful but most simple conditions. The movement outwards of the particles, causes currents in the opposite direction, and thus the nutrient material is brought into very close relation with, in fact within the sphere of action of, the living matter. The formed material in the ele- mentary parts of the tissues being as it were external to the germinal matter, in which all these changes go on, is con- tinually bathed with fresh particles of fluid, and this fluid is maintained in a state of constant motion. Were stagnation 104 THE STRUCTURE AND GROWTH to occur, changes would take place in the fluid correspond- ing to those which may be induced if it were kept at the temperature of 100 degrees for a short time out of the body. Decomposition would result, and in consequence, compounds would be set free, which would destroy the vitality of the germinal matter in the neighbourhood, and the death of this portion of the tissue would result. The stagnation of the fluids which bathe every part of every tissue will explain most satis- factorily many of the morbid changes which occur, especially in those tissues in which the activity of the changes in the normal state is not great, as in the fibrous tissues generally, cartilage, the thick walls of arteries, &c. In such textures various substances which ought to be removed in a fluid state become decomposed, and resolved into insoluble substances, some of which may be again taken up, while others, once precipitated, can never be removed except by the destruction of the tissue ; but here, I find myself led into making a long pathological digression, which I must now abruptly break off, as such an extensive subject as this must be considered separately. Neither is it possible, in a short course of lectures like the present, nor at this time would it be right to discuss the bearing of the views I have advocated upon the opinions generally entertained of the nature of disease. I may, however, be permitted again to allude to the very broad and important differences observed in the same texture, under varying conditions, with regard to the rapidity of multiplication of the masses of germinal matter, the proportion of formed material produced, the charac- ter of the formed material, its disintegration and the different products resulting therefrom in various cases. In scrofulous conditions there seems to be a tendency to the formation of a large quantity of germinal matter with the production of very little formed material, and this affecting not one but many tissues of the body. r lhe accumulation of formed material to an unusual extent, in certain important tissues, would seriously impair their function ; while, on the other hand, an unusually OF HUMAN TISSUES. 105 rapid disintegration of the formed material as occurs in fevers would be productive of a different order of morbid changes. Surely it almost amounts to a certainty that if we could study the different morbid processes in their minute detail, and ascertain their exact nature, and the precise order in which they were set up, we should be able to exert a much greater influence over them than we can at present. 106 THE STRUCTURE AND GROWTH LECTURE VI. On the Connective Tissue Series. Classification of Tissues. Areolar or Connective Tissue. Areolar- Tissue Corpuscles. Tendon and other forms of White Fibrous Tissue. Cartilage. " Mucous Tissue " of the Umbilical Cord. Fibrous Tissue formed from inflammatory Lymph. Bone. Dentine. Stellate Tissue on the surface of the Cementum. MR. PRESIDENT AND GENTLEMEN, WE have considered the nature of the bodies which are usually termed cells, and have traced the alterations which occur during different periods of their existence. I have endeavoured to show that these changes may be studied very satisfactorily if the elementary part of every living structure be regarded as consisting simply of matter in two different states or stages of existence germinal matter and formed material. The latter may be a firm, hard, unyielding, and comparatively permanent structure, existing for years without undergoing much change, or it may consist of a very soft and almost fluid substance which is altered very soon after its production and perhaps resolved into other substances as soon as it is formed. The germinal matter is active and living, and it possesses the power of animating lifeless matter infinitely under certain con- ditions. By its growth to a certain size and division into two OF HQMAN TISSUES. 107 or more, new masses are produced. In many cases the smallest visible particles of germinal matter, and in not a few instances particles too small to be visible under the highest magnifying powers yet made, have the power of maintaining an independent existence and of multiplication. By these processes new elementary parts having the same endowments as those from which they sprung, are produced. Nuclei or nucleoli, which originated as minute points in pre-existing germinal matter, may become new centres from which the same or a higher form of formed material may result. These nuclei, or nucleoli pro- vide for the continuance of the structure under adverse con- ditions, since they possess the power of resisting the action of agents which would destroy the germinal matter. "We pass now to the consideration of structures very different to u those which have hitherto engaged our attention. The question I am about to discuss is one of the most complex which has occupied anatomists, and it is one upon which there is much difference of opinion. Although the arrangement of certain tissues under the head of " connective tissues " has been gene- rally accepted, the greatest differences of opinon exist among observers as to the structure of many members of the series, and these differences of opinion are not slight and unimportant, but fundamental and essential. It will be probably in this class of tissues that facts adverse to the doctrine I have brought forward will be sought for, but a careful examination of these connective tissues will, I think, lead to the establishment of numerous points greatly in favour of my view. Many different modes of classification of tissues have been proposed, but the following, with slight modification, is more or less generally accepted : 1. Epithelial and allied cell structures. 2. Connective tissues. 3. A class which includes the higher tissues, the muscles, nerves, and vessels. 108 THE STRUCTURE AND GROWTH There are some objections to this classification. For instance, a muscle and nerve differ from each other more than either of them differ from certain forms of connective tissue, and the epithelium in some localities is as distinctly continuous with connective tissue as any two structures of the connective tissue group are with each other. The tissue lying beneath the skin and mucous membranes which is arranged so as to form areolse, or spaces communicating with each other, throughout the whole body was called cellular, and afterwards areolar tissue, and was supposed to connect or form a bond of union between the different tissues of the organism. Areolar tissue, it is asserted, has been demonstrated in all the glandular organs, between the elementary fibres of muscle, and around the nerve fibres where it forms the neuri- lemma. In the kidney this tissue is supposed to form a sort of supporting framework, in the meshes of which the special structures are contained, and by which they are connected together so as to form a compact mass. In some other glands the quantity of areolar is much greater, so that free movements of the elementary portions of the gland structure are permitted, as is the case in the mamma. The areolar tissue is now better known as connective tissue, and the tissues included in the class comprise some of the most important textures of the body. The connective tissue series is now universally admitted to be a most important, well-defined, and essential group. It seems to me, however, that many important facts militate against this arrangement. These textures are characterized by the presence of cells, or structures representing cells, and an intercellular substance ; and although there is much difference of opinion as to the manner in which these two structures are formed, all observers agree in admitting their existence. While some believe the bodies seen amongst the intercellular substance to be nuclei, others regard them as cells / but it is not necessary to enter at all into this discussion. The group contains mucous tissue (the connective OF HUMAN TISSUES. 109 tissue of the umbilical cord and the vitreous humour of the eye), the different forms of white fibrous tissue, tendons, fasciae, &c., yellow elastic tissue, cartilage, bones, and teeth. These tissues are very closely related to each other, and some pass one into the other. All may pass into bony tissue, and in many instances one may take the place of the other. But it must be observed that muscle and nerve and epithelium have also been proved, in certain localities, to be continuous with textures belonging to the connective tissue series. Great stress has been laid upon the fact of the continuity of many of these tissues with each other, but if what I have said of the mode of forma- tion of formed material (intercellular substance), and the relation of this to the germinal matter, be true, it follows of necessity that at the points where adjacent tissues are in contact the formed material of each must be continuous. I shall have to show you specimens of tendon, cartilage, and bone, in each of which masses of germinal matter (cells, nuclei, endoplasts], may be seen separated by a certain quantity of formed material (intercellular substance), and not only so but this formed material (intercellular substance), of tendon is inserted into, and is immediately continuous with, the corres- ponding formed material or intercellular substance of the bone and cartilage, in precisely the same manner as the formed material (intercellular substance) of the epithelium of the tongue was seen to be continuous with the corresponding trans- parent structure (connective tissue) of the papilla (prep. 17, Lecture II) . The mere continuity of tissue cannot therefore be accepted as a character of paramount importance in classification, and, as I have mentioned, muscular and fibrous tissue, and nerve and fibrous tissue, are as much continuous with each other as bone or cartilage and fibrous tissue. It appears, then, that the so-called connective tissues can- not be separated from other textures by very well-defined distinctive characters, and it is difficult to understand why 110 THE STRUCTURE AND GROWTH cartilage or bone, and fibrous tissue,, which are continuous with each other, should be considered as connective tissues while muscular fibre, and nerve fibre, which are also continuous with fibrous tissue, should be placed in a different class. The class of " connective " tissues has now become so large that there may be doubt in the minds of some as to the utility of a classification which divides all the tissues of the body into three classes, the first of which includes but one tissue (epithe- lium), the second only two (muscle and nerve), while the third (connective tissues) comprehends three times as many as are included in the two first classes ; and, while continuity of texture has been used as an argument for including numerons textures under the head of connective tissue, this continuity has been demonstrated to exist between certain tissues included in the two other classes with those of the connective tissue group. I shall endeavour to prove to you that a nerve fibre may become con- verted into a form of connective tissue, and hence according to this classification, a tissue which at one period of its existence finds a place in one class must be included at another period in a totally different class. Again, the division into cellular, fibrous or gelatigenous, sclerous, and other tissues, is equally objectionable, for the essential structure, mode of development, and growth of the so-called cellular and fibrous tissues are the same, and a cellular structure sometimes exhibits a fibrous character, a fact which is recognized by the use of the term fibre-cell. Whether the formed material is to be clear and structure- less, granular or fibrous, hard or soft, temporary or permanent, scanty or abundant, will depend, according to the proposed view, upon the powers of the germinal matter and the conditions under which it is placed. I have already brought forward instances in which ' cells' produce fibrous tissue, and have alluded to certain conditions under which the germinal matter of fibrous tissue gives rise to cells destitute of this structure. It appears OF HUMAN TISSUES. Ill to me therefore that any classification of tissues founded on these characters, so far from facilitating the study of this question, must render it more difficult, and the student will be much perplexed by the increasing number of exceptions which must be taken to the characters which are brought forward as essen- tial and specific. Virchow has advanced a step further in defining the character and raising the importance of the connective tissues. He states that in many of the soft connective tissues where the cells have a reticular arrangement, anastomoses takes place just as occurs between the canaliculi of bone or the branches of the dentinal tubes, and he professes to have demonstrated such tubes as different forms of ordinary connective tissue in tendon, mucous tissue, &c. " These anastomoses constitute a peculiar system of tubes or canals which must be classed with the great canalicular systems of the body, and which, particularly forming as they do a supplement to the blood and lymphatic vessels, must be regarded as a new acquisition to our knowledge, as in some sort filling up the vacancy left by the old vasa serosa which do not exist. This reticular arrangement is possible in cartilage, connective tissue, bone, and mucous tissue, in the most different parts ; but in all cases those tissues which possess anastomoses of this description may be distinguished from those whose elements are isolated, by the greater energy with which they are capable of conducting different morbid processes." Virchow considers that these areolar-tissue corpuscles exist- ing in relation with all the higher tissues and gland structures are the special seats of the formation of pus and cancer, and that the tissues in the immediate neighbourhood become infected through the anastomosing tubes. He doubts if cancer is propagated by really detached cells. I have only attempted to give you but a very hasty and imperfect sketch of the doctrines now generally held with regard to the connective tissue series. I propose, from time to time, in alluding to the specimens which I shall send round, to THE STRUCTURE AXD GROWTH draw attention to the bearing of the favourite doctrines held with reference to the nature of these important textures. The question of the existence of the nutrient tubes will be more fully discussed when we have considered the minute anatomy of some of the connective tissues. Let me beg you to examine the specimens which I shall send round without reference to any classification that may have been adopted, and I trust you will observe carefully the relation of the germinal matter to the formed material, as in the prepa- rations which I have already submitted to your notice. WHITE FIBROUS TISSUE. TENDON. You would think, perhaps, that there could be little doubt as to the anatomy of so simple a structure as tendon, and yet there is so much difference of opinion on the subject, and there are such contradictory statements with regard to the nature of the structures observed, that it would take more time than I have at my disposal to develop fully the views of Henle, Sharpey, Reichert, Eemak, Kolliker, and Yirchow, who have especially studied this matter. I must of necessity content myself with showing you a few specimens, and stating briefly the view I have been led to enter- tain with regard to the anatomy of this structure. As my conclusions differ from those generally held, it is hardly right to pass over the history of the subject, but my friend, Dr. Martyn of Bristol, has very lately given an excellent resume of these statements with some important observations of his own in a recent number of " Archives of the Medicine " (No. VI, 1860), and I shall, therefore, refer you to his paper. Tendon is generally examined after being dried, or partially dried, and moistened with fluid, but it has been found that these processes cannot be carried out without some alteration of the tissue being produced. The specimens I shall shew you have, therefore, been prepared without any desiccation at all. OP HUMAN TISSUES. 113 They have been soaked in carmine solution, and afterwards mounted in glycerine, according to the method I have already adverted to. No. 34 is a longitudinal section of a tendon of a child at birth. Observe the relation of the germinal matter to the formed material. The lines of oval masses of germinal matter are usually termed " the nucleated fibres of the tendon." No. 35, from the tendo Achillis of tne kitten, shows the numerous capillary vessels present in young tendon, which is much more vascular than that of the adult. No. 36 is a longitudinal section of a tendon from an old man, aged 74. The principal difference observed between this and Specimen 34, is the greater proportion of formed material or intercellular substance, to the germinal matter. A few deli- cate wavy fibres of yellow elastic tissue may be seen in different parts of the specimen. The "parallel nucleated fibres" are very distinct, but they are not nearly so close together as in Specimen 34 (Plate V, fig. 32, a b). Now, what is the nature of these so-called nuclei and nucleated fibres? If the tendon be stretched they form narrow lines, and the very elongated nuclei seera to be connected together by very delicate fibres. If the specimen be roughly handled, several nuclei may be detached, and they often assume an angular form with several projecting processes. If, on the other hand, they be stretched laterally, they become very wide, and assume an oval form. Longitudinal lines are seen in the oval masses, and these are caused by a tendency in the germinal matter to split in the longitudinal direction, or result from peculiar creasings or markings, which, when fully formed, give rise to the fibrous appearance so characteristic of this tissue. If you attempt to make a transverse section, you obtain the stellate bodies to which I have referred. It is impossible to obtain a very thin 114 THE STRUCTURE AND GROWTH transverse section of tendon with these nuclei in their natural position. In attempting to do so, you cut off short pieces of tendon with the included nuclei. At the edge of the specimen are some bands of wavy fibres detached, with the nuclei in them, and in some the immediate continuity of the fibrous structure with the so-called nucleus can be positively traced. The masses of germinal matter which you have seen in each specimen are regarded by Virchow as areolar or connective tissue corpuscles, a bindegewebs-k6rperehen," and he states that they are connected together by tubes, so as to produce a stellate arrangement. In a longitudinal section he admits that nothing of the kind is to be seen, but in a transverse section the stellate arrangement is observable. It seems to me that this may be explained thus : It is not possible to obtain a very thin section in which all the divided parts are in situ. In the transverse sections made, some of the prolongations from these bodies are altered in position, so as to make it appear as if they passed from the corpuscle or cell between and amongst the longitudinal fibres (Plate V, fig. 33). These nuclei are the masses of germinal matter of tendon, and the fibrous substance is the formed material formed from it. The so-called nuclei are certainly connected with the wavy bands of the fibrous tissue, figs. 31, 34, 36. The tissue nearest the nuclei is not yet perfectly formed, and it is so soft that separation usually occurs at this point, and the nuclei or cells escape from the substance of the fibrous tissue in which they appear to have been embedded. In the nutrition of this texture, therefore, it follows that the nutrient matter passes through, or permeates, the formed material, being drawn to the oval masses of germinal matter as towards centres. Certain of the nutrient elements then become living particles of the germinal matter of tendon, and in due order become converted into the firm, unyielding, fibrous struc- ture or intercellular substance (formed material). Acetic acid, as is well known, causes the wavy fibrous OF HUMAN TISSUES. 115 appearance to disappear, while it renders the so-called nuclei and their lines of connection with each other more distinct. At the same time in fully formed tendon there is a delicate network of yellow elastic tissue, the fibres of which for the most part pass round the bundles of the white fibrous tissue, and are therefore, upon the outer part in contact with the oldest part of the tendon, or with the formed material which was first produced. In fcetal tendon the acid does not produce so striking a change. The wavy bands, the fibrous appearance of which is not so very darkly marked as in the adult, in many cases remain ; and thin bands can always be detached and are easily demonstrated to be directly continuous with the so-called nuclei. In many specimens of young tendon it is difficult to demonstrate a single fibre of undoubted yellow elastic tissue. The yellow elastic fibres are always less numerous in young than in adult tendon, while the so-called nuclear fibres are two or three times more numerous in the former than in the latter. The proportion of yellow elastic tissue, therefore, does not seem to be dependent upon the so-called nuclei. The yellow fibres where they exist are not connected with the nuclei, and are separated from them by white fibrous tissue. These elongated parallel nuclei of tendon are not concerned in the formation of yellow elastic fibres, but the germinal matter of which they are composed does become converted into the white fibrous tissue of the tendon. This germinal matter, like that of other structures, and the fibrous material which it produces, when young and imperfectly formed, are not rendered transparent by acetic acid and other reagents, while the fully formed tissue undergoes the alteration which is so well known. I should state that I have studied the action of reagents on specimens which have been treated with carmine and soaked in glycerine. This latter substance possesses the property of retarding the action of chemical reagents, and by the slow and gradual effect produced it is advantageous. H 2 116 THE STRUCTUKE AND GROWTH Fig. 33, Plate V., shows the appearance of a small piece of a longitudinal section of the tendon of a child at birth. The prolongations from the masses of germinal matter (cells or nuclei] are well seen, and their communications are tolerably numerous. The specimen has been pressed, and the disposition of the oval nuclei has therefore been altered. The processes are distinct enough in some places, but most of them gradually become lost among the wavy fibres with which all are connected and of which they are but the early stage. Although they somewhat resemble fibres of yellow elastic tissue in their general appear- ance and in their power of resisting the action of acetic acid, they are not of this nature ; their outline is irregular, and when examined with very high powers they have a granular appear- ance, which is very different to the sharp outline and homo- geneous appearance of the yellow elastic tissue. In the dead tissue they may be called tubes, but they are artificial tubes, and do not convey nutrient juices during the life of the tissue. The germinal matter and imperfectly formed tissue of which they consist, cannot be regarded as a nutrient material. It is merely an early stage of the fibrous tissue. Moreover, it must, too, be borne in mind that the appearance so remarkably distinct in fig. 33, which results in part from the pressure to which this specimen has been subjected, is not constant. It is not seen in the specimen of adult tendon represented in fig. 34, where fibres of yellow elastic tissue are found, nor in that of the kitten, fig. 31, and in the fascia of the frog there is no more indication of such an arrangement than there is in cartilage. In some specimens of the tendon of the child which have been stretched and pressed, the appearance of stellate cells and communicating tubes is most distinct, but that it depends upon an alteration produced in the nuclei, and upon the displacement and tearing of some of the young tissue connected with them is sufficiently proved by the appearance being produced by pressure, by its absence in parts of the specimen not subjected to pressure, by the great variation in OF HUMAN TISSUES. 117 the appearances when the arrangement is produced, and by its entire absence in certain specimens. The dark lines in fig. 33, continuous with the cells, are not elastic fibres at all, neither are they elastic tissue at an early period of its formation, as wiD be shown. Elastic tissue when it exists in tendon is not connected with these nuclei. The altered appearances produced in the same piece of tendon by mere stretching and pressure are shown in Plate VI, fig. 34. The fact illustrated in the drawing is most important. The drawing was carefully copied from a specimen which exhibited the usual regular arrangement before pressure was applied, and m^ perhaps help to explain the cause of the different statements which have been made with reference to the appearance of the so-called cells or nuclei. How are we to account for the delicate fibres of yellow elastic tissue surrounding the fibres of many specimens of tendon ? Their existence is undoubted but they are not in suffi- cient number to be considered as essential constituents of the tissue, and they are not to be detected in all forms of white fibrous tissue. For the most part they wind round the bundles. By great patience you may occasionally succeed in finding a nucleus connected with these fibres, but when this is so the nucleus is very small, and quite distinct from those I have described as connected with the white fibrous tissue. It is, however, very seldom that I have been able to demonstrate this nucleus in connection with the yellow elastic tissue in tendon, and from the fact that I have seen this appearance result from alterations produced in an undoubted capillary vessel, I am disposed to explain the very few cases in which I have met with it in this manner. As a rule the fibres encircling the bundles of the white fibrous tissue are certainly not connected with nuclei. The nuclei which are constantly present, exhibit a linear arrange- ment at every period of the growth of tendon. The yellow elastic tissue on the other hand is not arranged in parallel lines, 118 THE STRUCTURE AND GROWTH but the delicate fibres of which it is composed form a lax network. As to the tubular nature of these fibres of yellow elastic tissue. In yellow fibrous tissue, from many situations I have seen prolongations of germinal matter as in other tissues, but I have completely failed to prove that these yellow elastic fibres generally are tubular, and concerned in the distribution of nutrient matter. Over and over again, I have stained the nuclei amongst the fibres of yellow elastic tissue with carmine, while not a single fibre exhibited the slightest alteration. I cannot think, therefore, that these fibres at any period of their existence, have any such office as that, of distributing nutrient fluid to the tissues in connection with which they are found. No. 37 (fig. 30) is a portion of the white fibrous tissue from the fascia covering the muscles of a frog, and this specimen is quite destitute of the yellow elastic tissue. The oval masses of germinal matter, coloured dark red with carmine, are, however, very distinct, and their continuity with the fibrous tissue is equally positive. Fig. 36, Plate VI, represents a vertical section of a piece of thick lymph lying between the liver and diaphragm, from a man who died of scrofulous enlargement or amyloid degenera- tion of the liver. The mass adhered slightly to the fibrous capsule of the liver, but it could be removed without being torn. In one or two places it adhered very intimately, and had under- gone conversion into white fibrous tissue, but the layer generally was not in vascular connection with the adjacent parts. Similar extensive layers of lymph were found over the surface of the intestines. The germinal matter and formed material can be seen most distinctly in the specimen, and the arrangement of the meshes of fibrous tissue is almost as regular as that observed in the proper tissue of the cornea. OF HUMAN TISSUES. 119 We, therefore, conclude that tendon, like fascia and other textures consists of germinal matter and formed material, and that the formed material bears the same relation to the germinal matter as in other tissues ; that the so-called nuclei of the nuclear fibres are the masses of germinal matter which produce the fibrous tissue of the tendon; that the elongated fibres intervening between the cells or nuclei consist of soft material undergoing the process of conversion into the harder fibrous tissue. This soft substance is soon broken down after death and liquefied, and these straight tubes, which are artifi- cially produced, seem to intervene between the oval masses of germinal matter, so that we have a series of straight tubes pursuing a longitudinal course in all parts of the tendon, and exhibiting here and there a dilated portion. This is not the only tissue in which oval masses of germinal matter form, as it were, straight continuous chains parallel to each other. In dentine, in the muscular fibres of the heart, in the muscles of the frog generally, and in some of the muscular fibres of insects, a similar continuity between oval masses of germinal matter is observed. These might be regarded as tubes containing granular matter, but this would be a very artificial view of these structures, and I think it more natural to speak of them as germinal matter surrounded by the formed material which they produce. In some cases they are found on one side of the fibre, the production of the formed material having taken place entirely on one side of the masses of germinal matter. There are no tubes or cavities in the living tissue ; the space is occupied with the most important part of the whole structure, the substance upon which the integrity of the whole and the reproduction of new tissue depend, and if this be destroyed during life, the destruction of the firm fibrous tissue must at length necessarily result, because the passage of fresh particles of fluid through its substance must cease, and in con- sequence the character of the fibrous tissue soon becomes altered. 120 THE STRUCTURE AND GROWTH Having fully considered the anatomy of that form of con- nective tissue of which tendons, fasciae, and ligaments are composed, we will now very briefly refer to another variety of this tissue. Different forms of connective tissue have been recognized by many observers, but it is generally believed that they are all formed in the same manner ; that the structure corresponding to the white fibrous element, which may exhibit distinct parallel markings, or may appear granular with no well- marked fibrous appearances, is an intercellular substance, and that the oval bodies seen embedded in this and the prolonga- tions from them, where they exist, represent the cells of other tissues. In my last lecture I shall bring forward evidence to show that many tissues which, after having existed in a state of functional activity for a certain time, waste and disappear, leave behind a certain quantity of transparent fibrous tissue, which is not completely removed by absorption. If muscle or nerve waste from any cause, a structure somewhat resembling white fibrous tissue remains behind, and in some cases a similar structure occupies the situation which was filled by a vessel at an earlier period. Let me draw your attention at once to the cord-like network of fibres in connection with the external coat of a small branch of artery. The specimen is taken from the abdominal cavity of a frog. (Figs. 26 and 27, Plate V.) Fig. 26, shows the appearance alluded to under a power of 130 ; a is the outer part of the muscular coat of the artery. A bundle of nerve fibres is seen running in the external coat of the artery, and at c some of the fibres are seen to leave the large trunk of the nerve and run in the central part of some of the fibrous cords. In fig. 27 a portion of one of these cords with most distinct nerve fibres is seen magnified 700 diameters, and a transition may be traced from most undoubted nerve fibres to the very narrow branching fibres seen in the upper part of the specimen. These fibres are not altered by OF HUMAN TISSUES. 121 acetic acid, but by careful examination it is clearly proved that they may be split up into finer fibres if they are not actually composed of sev.eral minute fibres collected together. They somewhat agree in character with the axis cylinder of a nerve fibre. Some of the finest of these cord-like fibres of connective tissue seem to consist of a transparent matrix, in which two or three nerve fibres are embedded. The transparent matrix is the so-called tubular membrane of the nerve fibre. I consider, therefore, that the nuclei and delicate fibres continuous with them, embedded in a more or less fibrous connective tissue, are nerve fibres which were functionally active at an earlier period of life, and that the matrix in which they are embedded corresponds to the so-called tubular membrane. At e, three very fine nerve fibres embedded in a matrix are represented, and the fibres represented at / are probably altered nerve fibres. There are in different parts of the frog, especially in connec- tion with the skin and areolar tissue beneath, cord-like fibres very much resembling those just described in their general appearance, but differing from them in the disposition of the nuclei and in the matter which passes between the nuclei, being granular and less fibre-like. Such fibres have the general appearance represented at b, fig. 35, and are composed of white fibrous tissue with its nuclei and their prolongations (formed material and germinal matter). The mode of development of these thick cord-like fibres of connective tissue is represented in fig. 35, from the cutis of the frog. At a, numerous oval nuclei are seen undergoing division which occurs transversely and longitudinally. The distance between each gradually becomes increased, and for some time granular matter may be seen intervening between one nucleus and the other. In this case a reticulated arrange- ment exists, as in certain forms of fibrous tissue (figs. 41, 43), and the fully formed tissue represented in fig. 356 forms a variety of connective tissue between tendon and fascia where 122 THE STRUCTURE AND GROWTH the nuclei form straight lines; and the outer part of the periosteum and areolar tissue generally, where they assume a stellate form. It is difficult to distinguish the points to which I have adverted in every individual case, but that fibres resembling elastic tissue in their behaviour with acetic acid, are immediately continuous with nerves, and remain in situations where nerves had been abundantly distributed at an earlier period of life will, I think, be fully proved in my last lecture. Permit me to sum up the prolonged discussion on this question in a few words. A tissue possessing the characters of white fibrous tissue may be formed like other tissues from germinal matter, or it may result from changes taking place in tissues which originally possessed much higher endowments. In the last case it may serve as a support to the new texture which is developed, and as life advances this tissue, the debris of more important struc- tures, becomes, in certain localities, moj-e abundant. Although it is true that many very different forms of white fibrous tissue exist, it is interesting to observe, in certain cases, the great similarity between the arrangement of the lowest temporary forms of this tissue, of which false membranes are composed, and that of the higher and more permanent forms of the struc- ture, as seen in tendon, fascia, and even the proper tissue of the cornea. (Figs. 28, 29, 30, 31, 32, 36.) CARTILAGE. Cartilage has long been the battle-ground for questions relating to cells, nuclei, cell-walls, and intercellular substance. For a statement of the different views now entertained upon the anatomy of cartilage, I must refer you to the following treatises : Kolliker's Manual, Quain and Sharpey, the transla- tion of Kolliker, by Professors Busk and Huxley, and Professor Huxley's article on the " Cell Theory," before referred to. OF HUMAN TISSUES. 123 Most recent observers agree in the opinion that the matrix or intercellular substance of cartilage (formed material) is produced independently of the cells (germinal matter). The proportion is, however, very different in different forms of cartilage, and in the same cartilage at different periods of growth. Young cartilage contains very little of the intercellular substance. In prep. 38, p. 9, at one view, you may see some of the youngest portions of the ensiform cartilage of the mouse and its connection with tendon to which muscular fibres are attached. The matrix of the cartilage is in direct continuity with the fibrous tissue of the tendon. Upon a careful exami- nation of this specimen you will observe that the youngest elementary parts are only separated from each other by a very thin line of formed material, and the germinal matter tinted with carmine, seems to shade gradually into the intervening substance. As you pass outwards you see the proportion of formed material between each oval mass, or between the col- lections of masses, of germinal matter gradually increasing. These very important points are most satisfactorily shown in specimens treated with carmine. As in other tissues, the relative proportion of the germinal matter to the formed material of cartilage, gradually becomes less as we pass from the youngest towards the older parts of the tissue, or, in other words as the elementary parts advance in age. No. 39 (fig. 41) is a thin section through the tendo Achillis and os calcis (in that part which is now cartilagenous) of a kitten soon after birth. In the centre of the specimen is a line marked by the existence of capillary vessels (a). This divides the cartilage from the tendon. Observe in this specimen how closely the two structures i-esemble each other in general appearance. The arrangement of the germinal matter and formed material is the same in both, except that in the tendon there is already an indication of parallel fibres. The proportion of the germinal matter and formed material is about the same 124 THE STRUCTURE AND GROWTH in both tissues. In the cartilage the masses of germinal matter divide, and the resulting portions at once become separate masses. In the tendon the masses divide, but the resulting portions are connected together for some time by a thin line of germinal matter. Between the cartilage and the tendon is a layer which eventually becomes the periosteum. The stellate arrangement of the masses of germinal matter (areolar or con- nective tissue corpuscles) is very distinct, and their character is retained in the adult tissue. In the drawing this layer is represented. (Fig. 41, b, Plate VII). Dr. Martyn compares the structure of porphyra with that of cartilage, and considers that the substance which is generally called intercellular is really composed of the old cellulose walls of the cells f ' modified by age, and pressed into angles by newly encroaching groups, these layers at length resemble a true intercellular substance.""* The specimens just passed round clearly prove that the matrix, or intercellular substance, exactly corresponds to the fibrillated substance of white fibrous tissue, the matrix of bone, &c., which is generally admitted, but they also confirm Dr. Martyn' s observations on the relation of the so-called capsides or cell walls to the intercellular substance. At an early period of development of all forms of cartilage, masses of germinal matter are seen situated very close to each other, and as the growth advances, the quantity of formed material between them (matrix, intercellular substance) gradu- ally increases. It is formed from the germinal matter. If you examine any of those cartilages in which small parcels of cells exist at intervals through the matrix, you will observe that there exists a greater amount of formed material between the various collections, than between any of the individual masses of each collection. If it be admitted that the matrix is formed from the masses of germinal matter this fact is at once explained. The more recent the division of the mass of ger- * Archives of Medicine, Vol. II, p. 99. OF HUMAN TISSUES. 125 minal matter the thinner will be the intervening layer of formed material between the resulting masses. In fig. 40 several elementary parts of cartilage from the frog are represented in different stages of growth. The manner in which the matrix is formed is, I think, easily understood after a careful examination of these specimens. At a, large oval masses of germinal matter are seen to be separated from each other by a very thin layer of soft formed material (matrix). At b, this has increased, but as the germinal matter grows, while the conversion of its outer portion into formed material pro- ceeds, the elementary part becomes larger. The next stage is shown in c. In d, e, f, g, h, growth has ceased, and the ger- minal matter gradually undergoes conversion into formed material until at last only what is termed the nucleus remains, and this in many instances dies and a small oval collection of granules, which are not tinged red with carmine, h, is all that marks the position of the germinal matter of the cartilage cells by which the matrix, or formed material, has been produced. After this has occurred the matrix may become harder and undergo other changes, but no more can be produced. The formation of the matrix has ceased. The matrix, close to the germinal matter which is recently formed is of course soft, and when it is broken away the mass of germinal matter within escapes entire. In all tissues the bond of union between the germinal matter and formed material is very slight ; a fact which receives a simple explanation upon the view of growth brought forward. The matrix gradually undergoes condensa- tion and probably contracts somewhat after it has been formed. In fig. 42 the formation of fat, a change which is not unfrequently observed in cartilage, is traced. A small globule of fatty matter, is first seen in the germinal matter of an ele- mentary part external to the nucleus (fig. 42 d), as this increases the nucleus is pushed over to one side, and gradually 126 THE STRUCTURE AND GROWTH becomes compressed between the fatty matter and the recently formed matrix of the cartilage. The changes occurring in cartilage during the formation of fatty matter resemble those which take place in the development of ordinary adipose tissue. The formation of cartilage is generally described in a very different manner. It has been said that the membranous capsule of the cartilage cell sends in septa when the cells it con- tains, undergo division " which serve as new envelopes for the young cells, yet in such a way, that even the gigantic groups of cells, which proceed from each of the original cells, are still enclosed in the greatly enlarged parent capsules/' (Virchow). Against this theory I have endeavoured to show that the matrix or intercellular substance with the membranous capsules of the cartilage cells corresponds with the cell wall of a spore of mildew, Plate II, fig. 10 a. This outer capsule of the mildew, as I have tried to prove, does not possess the power of growth. It is the internal germinal matter which is alone concerned in the growth of the plant. So in cartilage, the matrix was once in the state of germinal matter. The septa do not extend themselves in, or grow in, but the material of which they are composed results from an alteration taking place in the oldest particles of the germinal matter. Mucous TISSUE OF THE UMBILICAL CORD. Let me now ask your attention to the anatomy of a peculiar connective tissue which has been particularly studied by Virchow, and on the structure of which he lays the greatest stress, for he states that in a good preparation,