into fibres, or (on the contrary) be unable to form cells in consequence of deficient or low a-plastic power. The whole of this doctrine Virchow rejects as an entire mistake; and he refuses even to use the term exudation in the sense in which it has been used by the Vienna school, and adopted in England-i.e., as an effusion which may become organized. He does not, of course, refuse to admit the existence of transudations, but these he considers to be quite distinct from the plasmatic effusions to which the term exudation has lately been restricted. Our readers will no doubt at once say, "Are not pus cells formed on free surfaces-such as mucous membranes or the pleura, or in the interior of solid organs; and is not this from transformations of what was at first an amorphous exudation?" "Not so," reply Virchow and his followers; 66 every pus cell arises from a previous cell, it in no case originates de novo; your notion of a fibrine-looking plasma poured out on a mucous membrane or on the pleura, and forming pus by internal changes, is an entire mistake. Omnis cellula e cellulâ.”

How, then, does pus originate? we may ask. The answer of Virchow's school can be given, not only by the work we are reviewing, but by a reference to an essay on the doctrines of the origin of pus by Professor C. O. Weber, which has been published since the CellularPathology, and may be said to have received Virchow's implied sanction.*

To make it clear, however, to our busy readers engaged in practice, who are not familiar with the present discussions on histology, we must make a short digression, and refer to Virchow's opinion on the anatomy of areolar tissue. This opinion lies at the basis of many of his new views, and it must be explicitly understood.

If our readers will look at the last edition of Quain's Anatomy,' they will find a brief but perfect account of the views of Reichert and Virchow on the areolar tissue. Instead of regarding areolar tissue as a mass of individual fibres, Reichert described it in 1848 as an homogeneous substance, the fibrillation of which was produced by manipulation. In 1851, Virchow,t and, almost at the same time, Donders, described as dispersed through the homogeneous substance of the areolar or connective tissue certain cellular bodies, similar to, or identical with, the cells of cartilage and of bone (Bindegewebskörper). These bodies are described as round or spindleshaped cells, separated by intercellular homogeneous substance, and from them proceed exceedingly fine canals, which anastomose with the canals coming from other cells, and thus is supposed to be formed throughout the areolar tissue a vast communicating system of vessels, through which nutrient fluid can pass; and which, in fact, form a system of circulation subsidiary and complementary to the circulation in ordinary blood vessels.§

Zur Entwicklungsgeschichte des Eiters, von Prof. C. O. Weber, in Bonn: Virchow's Archiv für Pathol. Anat., Band xv. p. 465. 1859.

+ Identität der Knochen, Knorpel, und Bindegewebskörperchen: Würzburg Verhandl., Band ii. 1851.

Siebold and Kölliker's Zeitschrift, Band iii. p. 348.

§ See especially Wittich, in Virchow's Archiv, Band ix. p. 185. 1856. His experiments, however, have not succeeded with others.

This view has given rise to great controversy; and has been especially combated by Henle, whose immense experience and assured judgment necessarily give his opinion the greatest weight; while it has been more or less completely admitted by Leydig, Kölliker, and others, and has been adopted without hesitation not only by Virchow's immediate school, but by many (Professor Weber, of Bonn, for example) who cannot be considered as the special followers of Virchow.

Now, this view of the nature of the connective tissue is, we may say, a vital point in the doctrine of Virchow, for these corpuscles of the areolar tissue are made to play a most important part in pathology. From them are supposed to arise many, if not most, of the morbid growths; from them spring in many cases pus cells, and from them, in fact, is made to date the commencement of a vast number of pathological processes.

If this doctrine should be overturned, much of the newest pathological teaching rolls with it in the dust, and it is obviously of the greatest importance to be certain of the safety of so cardinal a point. In this country, the general opinion of the teachers of minute anatomy seems, as far as we know, to be one of hesitation and uncertainty rather than of denial or assent, and we presume that in Germany this feeling is also widely shared. Some of the latest observations on the development of areolar tissue appear not to give support to Virchow's opinions, and in spite of the familiarity with which Virchow's pupils speak of seeing the changes in the connective-tissue cells, it must be admitted that it is difficult to suppose the appearances can be so obvious when so many good observers are unable at present to convince themselves of the accuracy of the descriptions.

營

Still Virchow has no doubts, and as we are explaining his views, we shall express ourselves from his point of view, merely guarding ourselves from the imputation of giving more certainty to this view than can really be at present assigned to it.

As already said, the "connective-tissue bodies" are made to play so large a part in pathology, that it looks as if, like Aaron's rod, they were to devour all previous hypotheses. To say nothing of the changes in allied structures, such as cartilage cells, so well investigated some years ago by Redfern, and lately by Virchow and Weber, or the cells of the cornea as described by His,† or those of bone, the pathological conditions of the cells of the connective tissue proper are now made to embrace so wide a range, that if these views are confirmed, the usual descriptions of inflammatory conditions, and of tumours and growths of almost all kinds, will have to be modified. We shall see this more completely hereafter.

To return to the question of the origin of pus. As early as 1852, Virchow had shortly expressed his present views, and at a later period (1855 and 1856) had still more explicitly stated that pus is "always a product of a continual tissue-development." He now briefly recapitulates his opinions as follows:

Baur: Die Entwicklung der Bindesubstanz. 1858. Virchow has replied to late objections in a recent number of his Archiv (Band xvi. p. 1. 1859.)

† Beiträge zur normalen und pathol. Histologie der Cornea, von Dr. His. Basel, 1856.

"We see daily the formation of pus on surfaces, as well on the outer skin as on mucous and serous coats. We can most safely observe the formation where strata of epithelium naturally exist. If you follow the formation of pus on the outer skin without ulceration, you will see that the suppuration regu larly proceeds from the rete Malpighii. It consists in a growth and development of new elements in the same. In proportion as these elements grow, a separation of the harder layers of epidermis occurs, and a vesicle or pustule arises. The place where the suppuration principally occurs corresponds to the superficial layers of the rete, which are already passing into epithelium; if the membrane of the vesicle is detached, these (the layers) usually remain still on the upper skin. In the deeper layers it can be seen that the cellular elements, which originally have simple nuclei, gradually divide, the nuclei become more numerous; in the place of a single cell, many are present which are themselves provided with again dividing nuclei. This has been generally explained in this wise; it has been received that an exudation first occurs in which the pus is formed, and it is well known that many of the investigations on the formation of pus were made on these fluids. It was very conceivable, so long as the 'discontinual' cell-growth generally was not doubted, that the young cells should without more ado have been looked on as independent new formations, and it should have been believed that germs arose in the fluid, which gradually becoming more numerous, formed pus. But the fact is this, that the longer the suppuration lasts, so the more completely one range of cells after the other is implicated in the process of growth, and that while the vesicle is being elevated, the quantity of growing cells in it becomes ever greater. When a small-pox pustule is formed, a drop of clear fluid is first present, but nothing arises in it; it merely loosens the neighbouring parts.

"The process is exactly the same in mucous membranes. There is no mucous membrane which will not give rise to puriform elements under certain circumstances. Only a certain difference is always obvious. A mucous membrane is so much the more in a condition to produce pus without ulceration, the more perfectly it possesses pavement epithelium. All mucous membranes with cylinder epithelium are much less disposed to form pus; the matter which is produced is found on accurate examination to be only epithelium, though it may have a thoroughly purulent appearance. The intestinal mucous membrane-that of the small intestines, for example-almost never produces pus without ulceration. The mucous membranes of the uterus, of the tubes, which is often covered with a thick mass of entirely puriform appearance, separate almost always only epithelial elements; while on other mucous membranes -the urethra, for example-we observe copious discharges of pus, as in gonorrhea, without the least ulceration being present; that depends essentially on the presence of many strata of cell-layers, the upper of which form a sort of protection for the lower, so that the growth of these latter is secured for some time. The pus is finally thrown off by continually growing collections of pus, or there occurs simultaneously transudation of fluid which carries off the pus cells from the surface, just as in the secretion of semen the epithelial elements of the seminal canals form the spermatozoa, and coincidently a fluid transudes which carries these off. But the spermatozoa do not arise in the fluid; this is only the vehicle of their continued movement. In this way we frequently see fluid which cannot be looked on as the building-places for cells, exude on the free surfaces of the body. If at the same time there is a growing epithelial formation on the free surface, the elements loosened by the transudation will exhibit only growing epithelium.'

After some remarks on the forms of pus, mucus, and epithelium, and on the necessity of not confounding these three forms when developed,

* Cellular Pathologie, pp. 397-8.

66

that pus,

although they proceed from the same foundation cell, so mucus, and epithelial cells are pathologically identical parts, which can be substituted for each other, though they cannot perform each other's functions," Professor Virchow goes on to observe, that in deeper parts purulent formations proceed from the connective tissue.

"This deeper pus-formation occurs regularly in the connective tissue (Bindegewebe). In it occurs, first, an enlargement of the cells (Bindegewebskörperchen); the nuclei become divided, and for some time grow excessively. On this first stage follow very soon divisions of the elements themselves. In the environs of the irritated parts, where formerly single cells lay, double and manifold cells are later found, out of which arises generally a new formation of an homologous kind (Bindegewebe). More in the interior, however, where already the elements are largely filled with nuclei, heaps of little cells appear, which at first have the same direction and forms as the former connectivetissue corpuscles. Somewhat later we find here round collections, or diffuse infiltrations, in which the intermediate tissue is very scanty, and is continually more and more destroyed in proportion as the cell-growth extends.

"If this process takes place on an undestroyed surface, the yet adhering epithelial layers can be seen to pass over the irritated and somewhat swollen parts. The outermost layer of the intercellular substance is also preserved for a long time, while all deeper parts of the connective tissue are already filled with pus-corpuscles, are infiltrated or abscessed. Lastly, the surface gives way, or without giving way is directly transformed into a white diffluent mass. By and by these forms give the so-named granulations which always arise from a tissue, where in a small quantity of soft intercellular substance, more or less numerous round elements are embedded, at least, in the special growing stage of granulation. The more the surface is approached, the more do the cells, which in the deeper layers were more uni-nucleated, show divisions of the nuclei, and on the farthest limits these cells can no longer be distinguished from pus cells. A detachment of the epithelium then tends to occur, and then it may be that the ground-substance liquefies and the single clements become free. If the growth still goes on largely, the mass still continually breaks up, the elements accumulate on the surface, and a destruction goes on which continually invades the deeper tissues, and ever throws more elements on the surface-that is peculiarly an ulcer." (p. 400-1.)

In this description it will be seen that the idea of an exudation is altogether discarded, and that the whole process is one of growth, only the developed cells do not assume the epithelial form, or remain as normal cells of areolar tissue, but pass into that closely allied form of pus cell.

These views are still further developed by Weber, who has described very fully suppuration of the periosteum, of muscle, of nerve, and of skin, and who, in addition, has made various interesting observations which seem to show that epithelial cells are in many cases nothing but modified connective-tissue corpuscles, so that not only are the connective tissue, tendinous tissue, bones, and cartilage considered as of one family, but the epithelial formations must, it would seem likely, be included in the same class. Böttcher has also carefully examined suppuration of muscle, especially of the heart, and has shown that this depends on changes in the areolar tissue and its corpuscles, which this observer has traced in the tissue of the heart.

* Virchow's Archiv für Pathol. Anat., Band xiii. p. 227. 1858.

We quote part of the description of suppuration of the periosteum, as giving most completely Weber's opinions :

"I must first observe," writes Weber,* "that the connective-tissue cells of the periosteum form, as V. Wittich first showed by imbibition in tendons, an anastomosing network, which can be made visible by the application of diluted chromic acid, but the recognition of which requires some familiarity with the appearances of such networks. The cells of this network have usually a perfect spindle form, and lie arranged in longitudinal rows. The anastomoses are very delicate, and are best seen by further tearing out, or after the imbibition of colouring substances, especially and beautifully of carmine. After the application of acetic acid the cells appear most visible, and they are isolated by the use of hydrochloric or dilute pyroligneous acid. The cell wall lies indeed so close to the ground-substance that one could speak only of imbedded nuclei, did not the enucleation of the cells prove their existence. If now the periosteum is examined in a suppurating fracture (as is unfortunately often seen, and gives rise frequently to amputation), or in an amputation stump of a man dead soon after amputation, there is seen a membrane swollen with fluid, which can be readily drawn from the bone, and whose silver-glancing fibrous threads clearly appear. Perpendicular section through such a membrane shows only, particularly at the loosened parts, which are apparently moistened with a gelatinous exudation, appearances which are also met with in the healing of fractures without suppuration; the extreme (of these appearances) only occur, however, in the suppurating periosteum (also in caries), and also are only visible when the periosteum hangs in a suppurating wound, or passes into granulations. To learn the genesis of the appearances we must look at the periosteum at some little distance from the suppuration. We see here, in all the above referred to cases, the nuclei of the connectivetissue corpuscles increase by division, with attendant enlargement of the original cellular space; the cells are then sometimes globular, sometimes retain their usual spindle form; finally, large spaces are formed which are entirely filled with round nuclei, which contain one, two, three, or five nucleoli, and exactly resemble pus bodies. Not infrequently one sees also divisions of the cells themselves; in the place of the spindle-shaped body, we see an indented cell, then two conical cells touching by their bases, then finally three or more, in them again growing nuclei. The capillaries of the periosteum are thickly covered with similar pus cells, which evidently arise from growth of the sonamed nuclei of the capillary walls.

and

"The pus formation in the periosteum follows, therefore, according to my observations, chiefly an intra-cellular course, yet there can decidedly occur division of the connective-tissue corpuscles into cells."+

As in the periosteum so in the suppuration of muscles, the pus cells form in the so-called nuclei, which Böttcher has shown to be nothing but the nuclei of connective-tissue bodies with extremely delicate walls, which interlace among the muscular fibres and run into the tendons, from which they can be coloured by imbibition. According to Weber and Böttcher, these bodies can be seen without preparation in fatty degeneration, in scirrhus, cancroid, and sarcoma; while in fresh and healthy muscle it is extremely difficult to see them without preparation in diluted chromic acid, or after imbibition with carmine. Weber gives a drawing of a suppurating and fatty gastro-cnemius, in which

* Virchow's Archiv, Band xv. p. 477. 1859.

† Weber: op. cit., p. 477-80.