ogy is concerned, gradually demolished. The formation of tissuecells from the egg and its partition has been observed throughout the whole animal kingdom. Apparently eggless animals, such as the cestoids and trichinæ, have one after the other been brought under Harvey's law; we know their eggs, their embryos, and their wanderings. There remains, in fine, but one great domain, though this is of the highest importance: it belongs particularly to pathology, and is that of the plastic exudates, which accompany the most important clinical processes, particularly the inflammatory.

It will readily be understood that so essentially pathological a subject would have but little interest for pure natural philosophers. They left it to medical men, who have to occupy themselves with it all day long. But in medicine this territory was held sacred; no one doubted that therein spoke old, well-attested experience. We old students were endowed with the so-called theorem of the plastic exudates from our earliest studies. Translated into our latter-day parlance, such a theorem would recognize discontinuity in most pathological new formations; it would establish and this is well worthy of note-the grounds for the dogma of the origin of life from non-living matter. Experience has taught us the exact opposite.

Permit me here, gentlemen, to speak a little more personally than is elsewhere my intention. Perhaps it will be more intelligible to the students of this hospital, and will make more impression if I narrate how I myself arrived at quite other views.

It was towards the end of my academical studies, more than fifty years ago, that I had to take up the work of assistant in the ophthalmic clinic of the Charité Hospital at Berlin. My attention was at once directed to the diseases of the cornea. We had severe cases of keratitis, but I saw in them no exudation; numerous cataract operations were performed and the wounds closed, but not by plastic exudation; this was absent from all corneal scars. Could this be explained by the circumstance that the cornea, apart from its circumference, is a non-vascular tissue? My interest was at once focussed on the non-vascular tissues. I turned first to the articular cartilages, and behold, here also I found the greatest changes without the presence of exudation, or, at any rate, of plastic exudation. I need only recall the form of inflammation which I named arthritis chronica deformans, and which is described by French physicians as arthrite sèche. My experimental studies on the inflammation of the walls of blood-vessels showed that the equally non-vascular intima of the larger arteries, and in part also that of the veins, can undergo great changes without even a trace of exudation being produced. Later on anatomical investigations on endocarditis led to the same result, provided that parietal thrombi were not regarded as exudations. But in all these cases and in every place there were found changes in the tissue-cells, active such as swelling, multiplication of nuclei, etc., or passive, as fatty degeneration.

I next turned my attention to vascular organs, and in particular

to those which were recognized by pathology as the common seats of exudation-processes. I refer, first, to the medullary infiltration of the lymphatic (follicular) tissue of the intestine and mesenteric glands in typhoid fever so strikingly depicted by the Vienna school: instead of the amorphous albuminous exudate which was described, I found only cells, and cells of the same kind as those which are normally present in these situations. The same was revealed in the so-called caseous exudates which were at one time ascribed to scrofula, at another to tuberculosis; the cheesy material was admittedly in the main amorphous, but it was in reality not an exudation at all, above all, not a primary product of disease, but rather the secondary product of degenerative necrobiotic changes in parts of the tissues, which had formerly been organized and not infrequently actually hyperplastic.

It is not necessary to go further into details in order to show how great is the realm of this pseudo-exudative process. But I cannot help referring to another series of morbid processes affecting the bones. It was whilst studying rickets that I first learnt the biological significance of the cartilage-corpuscles, the nature of which had till then been interpreted in very different ways. I believe that I was the first to distinguish in these corpuscles what must be actually recognized as cells from the merely capsular and extracellular coverings. The rachitic disturbance now brought into fullest evidence an appearance which was repeatedly misunderstood even by later observers; this was the increase of these cells by division, and the consequent growth of the cartilage.

It was not difficult to follow out the direct transition of the epiphysial cartilage into the periosteum of the neighboring bone, and thus into connective tissue. At this time the whole world was convinced of the correctness of the statement made by Duhamel that increase in thickness in the long bones was affected by the periosteal vessels exudating a nutritious juice, out of which the new bone substance was formed. Pathologists had extended this formula to periostitis and the formation of exostoses and hyperostoses; they assumed that between the periosteum and the bone a plastic exudation was excreted and stored up, in which the new osteophyte arose by secondary organization. The consequence of my investigations was that in not one of these spots, neither in the cartilage nor in the periosteum, neither in normal growth nor in rickets or periostitis, was organization preceded by the presence of a recognizable amorphous exudation. On the contrary, it was indubitably shown that the first stage of the changes was an active productive process of cell-multiplication; that at the same time the intercellular substance altered in character and underwent a series of successive changes till it assumed an osteoid appearance; and that then, and not till then, followed calcification and true ossification. There was also no difficulty in adducing the proof that the separate stages of these processes in cartilage and in periosteum ran a perfectly parallel

course, although the new tissue was in the one case at first true. cartilage, in the other only cartilage-like. If one wishes to designate this process in general it must be called proliferation. Most of these processes are of the nature of proliferation. Whoever calls the proliferative layer an exudation will never obtain an objective view of the actual proceeding.

There is thus not the slightest necessity for the genuine observer to hold to the arbitrary and totally erroneous formula of a plastic exudation. There is no such thing as a plastic exudation which is ever simply amorphous; the cells which may be found in it have not arisen there. With this proof, which can be obtained in numberless other places, the doctrine of the discontinuous origin of pathological new formations is set aside. Every such new formation presupposes a tissue from which its cells arise; this is its matrix. There is no difference in principle between the descent of men and animals from one mother and the descent of pathological new formations from one matrix. Pathology has been somewhat late in arriving at the knowledge of this correspondence, but I think that it has acquired especial value for biology in general.

In order to avoid misunderstanding, it may be noted that not every living cell is capable of becoming a matrix. All cells which are destined for the highest animal functions prove sterile, or at least very hypothetically capable of proliferation. Ganglion-cells, primitive muscle-bundles, red blood-corpuscles do not come under consideration as regards the theory of pathological descent. The more indifferent cells, on the other hand, above all those of cartilage, connective tissue and epithelium exhibit a marked proclivity to bring forth new cells. Many cells again, such as bone-corpuscles and fat-cells, require a special preparatory metaplastic stage before they can produce a new brood.

Proliferation is an active property of special cells. That it cannot be performed by all cells alike in no way alters the fact that it can only be performed by cells. It is just as little a function of an entire organism, for this itself would then have to be unicellular. In this property lies the explanation of the origin of a whole organism from a single egg-cell, that wonderful process which comes to pass but once in the life of an animal. Once tissues have arisen, each cell of a matricial tissue may, in respect of proliferation, be compared to an ovum; it brings forth a new progeny from which new tissue grows. This tissue bears, as a rule, the stamp of its matrix-it is built on the maternal type. This is the nature of descent, and herein lies the key to the knowledge of heredity, that puzzling appearance with which mankind has ever busied itself.

According to the humoral theory heredity was derived from the body-fluids and in particular from the blood. According to this idea the blood furnished the means of the continuance of the family. and the race; blood-relationship explained the similarity not only of the juices but also of the organs and the whole body. The blood

according to its nature determined the goodness or badness of the organization; noble blood generated noble men and healthy organs, bad blood a debased posterity and organs predisposed to disease. In scientific works naught remains of these fantastic surmises; they persist like a superstition in lay circles, but no one now maintains their correctness in serious debate. In their stead has arisen the recognition of the particular value of the mother tissue and its cells. These are the factors of inherited properties, the sources of the germs of new tissues and the motor power of vital activity.

During the development of a higher organism the constitution of the individual tissues changes; they become differentiated by means of metaplastic processes which are in their turn connected with cells and cell-territories. Thus it comes about that people have for ages spoken of dissimilar parts. The complete full-grown organism is built up of similar and dissimilar tissues; their harmonious working gives the impression of a unity of the whole organism which is, as a matter of fact, non-existent. For the further the organism develops the more its social constitution comes into evidence. It consists of innumerable independent parts which together constitute a single social body. If we take the ultimate elements of these parts we must call them all without exception cells, for cells alone are truly alive and scientific judgment is in the last instance concerned with them.

So little is the whole organism a definite unit that the number of its living constituents is in the highest degree inconstant. Looking at the gross structure of organs we are accustomed to regard a certain number of them as typical peculiarities of human beings or the various genera and species of animals. We expect to find two of each paired organ and one of each unpaired in a single individual. Man, like all other mammals, has a fixed number of bones and teeth and these numbers are rightly used as diagnostic of man or of the particular variety or species of animal. But these numbers form no essential condition of existence; a man with six fingers or seven toes remains a man, just as a lung with supernumerary lobes or a kidney with an excess of coni medullares remains a lung or a kidney. A woman with three, four or even more mammary glands is thereby no more a lower animal than a man with a tail would be. These are theromorphs ("sports") which can have no influence on our opinion as to the sex of the affected individual or its position in the animal scale.

6.

But it will be a long time before general opinion on the significance of sports" will, even among experts, become unanimous. One sect will connect them with descent, and see in them a proof of atavism; while the other will regard them only as a pathological formation, and will trace this back to an acquired lesion. During the last century we have gone through violent disputes as to whether certain malformations were inherited or acquired. Those who pinned their faith to inheritance had very generally the arriére

pensèe that the variation was atavistic, and the question soon presented itself as to whether the atavism was derived only from human ancestors, or whether one would have to go back as far as the lower animals to account for it. A universally valid explanation of theromorphism has not yet been found. In my opinion it will never be found. Each single example must be separately studied and explained, and the general value of this explanation will be by no means increased if we find atavism in any single case. Doubtless

an acquired variation can also be transmitted, and the circumstance that it is animal-like (theroid) does not go to prove a not acquired but atavistically transmitted condition. In connection with this I may refer to my paper on Race-Formation and Inheritance.* I can here discuss only the principal ground for the disputes regarding hereditary diseases which are special to pathology.

Medical men are accustomed to describe as hereditary all diseases which reappear in different generations of the same family. Thus one speaks of hereditary arthritis, hereditary tuberculosis, hereditary cancer. It is in fact not difficult to produce genealogical tables which demonstrate the recurrence of a paternal or maternal disease in children or grandchildren. Much trouble has been devoted, in my opinion without result, to seeking the germs of such diseases in the ovum or the semen. One is hence compelled to pass on to generations of cells which took origin after conception. Here we reach what Roux has designated the post generative formations. The further we pass away from the time of conception the more numerous examples do we find of alterations in the formation of cells and in the formation of embryonic tissues. But there is at the same time the greater possibility of the alteration having arisen after the formation of the first cells, and hence that the existing cause may have commenced to act at that time. If we set aside this possibility nothing else remains but to assume that from conception, or even from the organs which produced the ovum or the spermatozoon, a predisposition is transmitted which is already present in the earliest cells, even if it cannot be recognized in them.

Upon this theory are built up all interpretations of the inheritance of pathological and, we may add, physiological structures. There are, for example, many extraordinary anomalies in the disposition of hair, either through excess or through defect, and nothing is more common than to see the inherited transmission of such anomalies. But hairs are post-generative structures, and a disturbance in their development can make its first appearance only in a latter period of fetal life; not infrequently, indeed, it is first seen after birth. If such a peculiarity recurs through many generations in the branches of a family or a race it is called hereditary, and referred to a hereditary predisposition. But as undoubtedly excesses as well as defects in hairiness are brought about by acquired disturbances, such as actual diseases, it becomes necessary to seek a recognizable

* Published in the "Bastian-Festchrift," Berlin, 1596, pp. 33-39.