In his view of the metamorphosis of the aortic arches in the chick the first two pairs disappeared completely, the third pair gave rise to the arteries of the head and the fore-limbs, the right side of the fourth arch became the aorta, the left half of the fourth and the right half of the fifth arch became the pulmonary arteries, while the left half of the fifth arch disappeared. This schema, which for the last three arches was the same as Huschke's, von Baer upheld for the chick even in the second volume of his Entwickelungsgeschichte (p. 116); he rectified it, however, for mammals in the same volume (p. 212), deriving both pulmonary arteries from the fifth arch, and the aorta from the fourth left. He fully recognised the great analogy of the embryonic arrangement of gill-arches and gill-arteries in Tetrapoda with their arrangement in fish (i., pp. 53, 73).

Huschke, in a paper of 1832,[191] chiefly devoted to the development of the eye, figured and described the developing upper and lower jaws, and maintained against von Baer that the first slit turns into the auditory meatus and the Eustachian tube.

These were the first papers of the embryological period. Before going on to discuss the principles which guided embryological research during the next ten or twenty years it is convenient to note what were the main lines of work characterising the period.

The typical figure of the period is Rathke, who produced a great deal of first-class embryological work. He was, even more than von Baer, a comparative embryologist, and there were few groups of animals that he did not study. His first large publication, the Beitraege zur Geschichte der Thierwelt (i.-iv., Halle, 1820-27), contained much anatomical work in addition to the purely embryological; he commenced here his series of papers on the development of the genital and urinary organs, continued in the Abhandlungen zur Bildungsund Entwickelungs-Geschichte des Menschen und der Thiere (i., ii., Leipzig, 1832-3). A fellow-worker in this line was Johannes Mueller, whose Bildungsgeschichte der Genitalien (Duesseldorf) appeared in 1830.

In a memoir on the development of the crayfish which appeared in 1829,[192] Rathke found in an Invertebrate confirmation of the germ-layer theory propounded by Pander and von Baer. He was greatly struck by the inverted position of the embryo with respect to the yolk. In following out the development of the appendages he noticed how much alike were jaws and legs in their earliest stage, and how this supported Savigny's contention that the limbs of Arthropods belonged to one single type of structure. In his paper (1832) on the development of the fresh-water Isopod, Asellus,[193] Rathke returns to this point. Commenting on the original similarity in development of antennae, jaws and legs, he writes, "Whatever the doubts one may have reserved as to the intimate relation existing between the jaws and feet of articulate animals after the researches of Savigny on this subject and mine on developing crayfish, they must all fall to the ground when one examines with care the development of the fresh-water Asellus" (p. 147 of French translation).

Further comparative work by Rathke is found in the two volumes of Abhandlungen and in a book, Zur Morphologie, Reisebemerkungen aus Taurien (1837), which contains embryological studies of many different types, including a study of the uniform plan of arthropod limbs. Later on Rathke devoted himself more to vertebrate embryology, producing among other works his classical papers on the development of the adder (1839), of the tortoise (1848), and of the crocodile (1866). He laid the foundations of all subsequent knowledge of the development of the blood-vascular system in a series of papers of various dates from 1838 to 1856. The diagrams in his paper on the aortic arches of reptiles (1856) were for long copied in every text-book.

Rathke was a foremost worker in another important line of embryological work, the study of the development of the skeleton and particularly of the skull. We shall discuss the history of the embryological study of the skull in some detail below; meantime, we note the two other important lines of research which characterise this period. One is the intensive study of the development of the human embryo, a study pursued by, among others, Pockels, Seiler, Breschet, Velpeau, Bischoff, Weber, Mueller, and Wharton Jones.[194] The other important line—the early development of the Mammalia—was worked chiefly by Valentin,[195] Coste,[196] and, above all, by Bischoff, whose series of papers[197] was justly recognised as classical.

What interests us chiefly in the work of this embryological period is, of course, the relation of embryology to comparative anatomy and to pure morphology. The embryologists were not slow to see that their work threw much light upon questions of homology, and upon the problem of the unity of plan. Von Baer, we have seen, recognised this clearly in 1828; Rathke, in one of his most brilliant papers, the Anatomisch-philosophische Untersuchungen ueber den Kiemenapparat und das Zungenbein (Riga and Dorpat, 1832), used the facts of development with great effect to show the homology of the gill-arches and hyoid throughout the vertebrate series; Johannes Mueller made great use of embryology in his classical Vergleichende Anatomie der Myxinoiden (i. Theil, 1836), and, according to his pupil Reichert, firmly held the opinion that embryology was the final court of appeal in disputed points of comparative anatomy;[198] Reichert himself in a book of 1838 (Vergleichende Entwickelungsgeschichte des Kopfes der nackten Amphibien) discussed the two different methods of arriving at the "Type"—the anatomical method of comparing adults, and the embryological method of comparing embryogenies. Of the embryological method, he says, "Its aim is to distinguish during the formation of the organism the originally given, the essence of the type, and to classify and interpret what is added or altered in the further course of development. Embryologists watch the gradual building up of the organism from its foundations, and distinguish the fundament, the primordial form, the type, from the individual developments; they reach thus, following Nature in a certain measure, the essential structure of the organism, and demonstrate the laws that manifest themselves during embryogeny" (p. vi.). The embryologists, influenced in this greatly by von Baer, gradually felt their way to substituting for the "Archetype" of pure morphology what one may perhaps best call the embryological archetype. How the transition was made we can best see by following out the course of discovery in one particular line. We choose for this purpose the development of the skull, a subject which excited much interest at this time and upon which much quite fundamental work was done, particularly by Rathke and Reichert.

Following up his discovery of gill-slits and arches in the embryos of birds and mammals, Rathke in two papers of 1832[199] and 1833[200] worked out the detailed homologies of the gill-arches in the higher Vertebrates. He describes how in the embryo of the Blenny there is a short, thick arch between the first gill-slit and the mouth. A furrow appears down the middle of the arch dividing it incompletely into two. In the anterior halves a cartilaginous rod is developed which is connected with the skull; these rods become on either side the lower jaw and "quadrate." In the posterior halves two similar rods are formed which develop into the hyoid. The hyoid is at first connected with the skull, but afterwards frees itself and becomes slung to the "quadrate." From the hinder edge of the hyoid arch grows out the membranous operculum, in which develop later the opercular bones and branchiostegal rays. The upper jaw is an independent outgrowth of the serous layer.

The serial homology of the lower jaw and quadrate with the hyoid and with the true gill-arches was thus established in fish, and Rathke had little difficulty in demonstrating a similar origin of lower jaw and hyoid in the embryos of higher Vertebrates. He could even, as we have noted before, find the homologue of the operculum in a flap which grows out from the hyoid arch in the embryo of birds.

But Rathke could not altogether shake himself free from the transcendental notion of the homology of jaws with ribs, and this led him to draw a certain distinction between the first two and the remaining gill-arches, by which the homology of the former with the ribs was asserted and the homology of the latter denied. He thought he could show that the skeletal structures (lower jaw, "quadrate," and hyoid) of the first two arches were formed in the serous layer, just like true ribs, and like them in close connection with the vertebral skeletal axis. The other, "true," gill-arches appeared to him to be formed in the mucous layer, in the lining of the alimentary canal. They had no direct connection with the vertebral column, and seemed therefore to belong to what Carus[201] had called the visceral or splanchno-skeleton. He did not, however, let this distinction hinder him from asserting the substantial homology of all the gill-arches inter se, the first two included.

Rathke's discoveries relative to the development of the jaws, the hyoid and the operculum, enabled him to make short work of the homologies proposed for them by the transcendentalists. He could prove from embryology that the jaws were not the equivalent of limbs, as so many Okenians believed. He could reject, with a mere reference to the facts of development, Geoffroy's comparison of the hyoid and the branchiostegal rays in fish with sternum and ribs. He could show the emptiness of the attempts made by Carus, Treviranus, de Blainville and Geoffroy, to establish by anatomical comparison the homologies of the opercular bones, for he could show that these bones were peculiar to fish, and were scarcely indicated, and that only temporarily, in the development of other Vertebrates.[202] He did not, however, himself realise the relation of the ear-ossicles to the gill-arches, though he knew that Spix and Geoffroy were quite wrong in homologising them with the opercular bones in fish. He described, it is true, the development of the external meatus of the ear and the Eustachian tube from the slit which appears between the first and the second arch, as Huschke had done before him; he described, in confirmation of Meckel, the "Meckelian process" of the hammer running down inside the lower jaw; but the discovery of the true homologies of the ear-ossicles was not made until a year or two later by Reichert.

In his further study of the development of Blennius viviparus, Rathke observed some important facts about the development of the vertebral column and skull. He found that the vertebral centra were first formed as rings in the chorda-sheath, which give off neural and haemal processes. The vertebra later ossifies from four centres. The chorda (notochord) is prolonged some little way into the head, and the base of the cranium is formed by the expanded sheath, which reaches forward in front of the end of the notochord. This cranial basis shows a division into three segments, in which Rathke was inclined to see an indication of three cranial vertebrae. (It turned out that this division into three segments did not really exist, and Rathke later acknowledged that he had made an error of observation.) The side walls of the skull grow out from this base and form a fibrous capsule for the brain. The cranial section of the chorda itself shows no sign of segmentation; but later on the cranial portion of the chorda-sheath ossifies, like the vertebrae, from several centres. The vomer, which, in the classical form of the vertebral theory of the skull, was the centrum of the fourth, or foremost, cranial vertebra, does not, according to Rathke, develop in continuity with the cranial basis and the chorda sheath, but develops separately in the facial region.

Von Baer, like Rathke at this time, was also to some extent a believer in the vertebral theory of the skull. In his second volume (1834, pub. 1837) he holds that the development of the skull, as the sum of the anterior vertebral arches, is in general the same as that of the other neural arches, and is modified only by the great bulk of the brain (Entwickelungsgeschichte, ii., p. 99). He had, however, some doubts as to the entire correctness of the vertebral theory, doubts suggested by a study of the developing skull. "In the course of the formation of the head in the higher animals, something additional is introduced which does not originally belong to the cranial vertebrae. At first we see the vertebration in the hinder region of the skull very clearly. Afterwards it becomes suddenly indistinct, as if some new formation overlaid it" (i., p. 194).

Even more clearly is his doubt expressed in his paper on Cyprinus. "Upon the formation of the vertebral column only this need be said, that at this stage the notochord is very clearly seen, and the upper and lower arches and spinous processes are visible right to the end of the tail, but the separation into vertebrae ceases abruptly where the back passes into the head. I do not hesitate to assert that bony fish, too, have at this stage an unsegmented cartilaginous cranium (as cartilaginous fish have all their life), the prominences and hollows of which constitute its only resemblance with the vertebral type" (1835, p. 19).

A convinced supporter of the vertebral theory was Johannes Mueller, who, in his classical memoir on the Myxinoids,[203] discussed at some length the relation between the development of the vertebrae and the development of the skull. His memoir is principally devoted to comparative anatomy, but in treating of the skeleton he pays much attention to development. He describes the formation of the vertebrae in elasmobranch embryos; for the facts regarding other Vertebrates he relies largely on work by Rathke (Blennius, 1833) and Duges (1834). He recognises as the basis of his comparisons the homology of the notochord in all vertebrate embryos with the persistent notochord which forms the chief part or the whole of the vertebral column in the Cyclostomes. The notochord possesses an inner and an outer sheath and the outer sheath is continuous with the basis cranii (p. 92). It is in the outer sheath that the vertebrae develop—from four separate pieces, in fish at least, plus an additional element which helps to form the centrum. The skull of Vertebrates consists, according to Mueller, of three vertebrae, whose centra are the basioccipital, the basisphenoid and the presphenoid. Other bones besides those belonging to the vertebrae are present, but this formation out of three vertebrae gives the essential schema for the skull. Now the brain capsule, like the sheath of the spinal cord, is a development from the outer sheath of the notochord. If the skull consists of vertebrae we should expect the centra of the skull-vertebrae to develop in the outer sheath at the sides of the cranial section of the notochord as two separate halves, just as do the bodies of the vertebrae; we should expect further the cartilaginous side-walls of the cranium to develop in the membranous brain-sheath just as the neural arches develop in the membranous sheath of the spinal column. In Rathke's discovery (!) of a segmentation of the basis cranii into three parts, and of the isolated formation of the vomer, Mueller sees a confirmation of his view that the skull is composed of three and not four vertebrae. But there is nothing in Rathke's observations to support the idea that the centra of the cranial vertebrae are formed from separate halves. Mueller has to be content with a reference to the state of things in Ammocoetes (which, by the way, he did not know to be the young of Petromyzon). In the simple skull of Ammocoetes the base is formed chiefly by two cartilaginous bars lying more or less parallel with the longitudinal axis of the skull and embracing with their hinder ends the cranial portion of the notochord.

These bars, declares Mueller, are clearly the still separate halves of the pars basilaris cranii, and represent the divided centra of the two hinder cranial vertebrae. To complete the parallel between the development of the skull and of the vertebrae, it would have been necessary to show that the side walls of the cranium developed in a similar manner from separate pieces. Mueller could not prove this point from the available embryological data, and indeed the facts which he did use had to be twisted to suit his theory. A curious apparent confirmation of his idea that the centra of the cranial vertebrae are formed from separate halves was supplied in 1839 by Rathke's discovery of the trabeculae in the embryonic skull of the adder.

The next big step in the study of the development of the skull was taken by a pupil of Mueller, C. B. Reichert, who showed in his work very distinct traces of his master's influence. Reichert's first and most important contribution to the subject was his paper on the metamorphosis of the gill, or, as he called them, the visceral arches in Vertebrates,[204] particularly in the two higher classes. Reichert describes the similar origin in embryo of bird and mammal (pig) of three "visceral" arches. These arches stand in close relation to the three cranial vertebrae which Reichert, like Mueller, distinguishes. He makes the retrograde step of admitting only three aortic arches, and he is not inclined to consider the three visceral arches as equivalent to the gill-arches of fish—in his opinion they have more analogy with ribs, though differing somewhat from ribs in their later modifications. The visceral arches are processes of the visceral plates (von Baer), which grow downwards and meet in the middle line, leaving between one another and the undivided body wall three visceral slits opening into the pharynx. The first visceral process is different in shape from the others, for it sends forward, parallel with the head and at right angles to its downward portion, an upper portion in which later the upper jaw is formed. The other two processes are straight. From the hinder edge of the second visceral arch there develops, as Rathke had seen, a fold which is comparable with the operculum of fish. The first slit develops externally into the ear-passage, internally into the Eustachian tube, and in the middle a partition forms the tympanic ring and tympanum. Inside each of the visceral processes on either side a cartilaginous rod develops. In the first process this rod shows three segments, of which the first lies inside that portion of the process which is parallel with the head. This upper segment forms the foundation for the bones of the upper jaw. The lowest segment of the cartilaginous rod becomes Meckel's cartilage, and on the outer side of this the bones of the lower jaw are formed. The middle segment becomes in mammals the incus (one of the ear-ossicles), and in birds the quadrate. Meckel's cartilage, which was discovered by Meckel[205] in fish, amphibians and birds, is a long strip of cartilage which runs from the ear-ossicle known as the hammer in mammals,[206] to the inside of the mandible. Reichert shows how this relation comes about. The hammer, according to his observations on the embryo of the pig, is simply the proximal end of Meckel's cartilage, which later becomes separated off from the long distal portion (see Fig. 9). The third ear-ossicle of mammals, the stapes, comes not from the first arch but from the second. The cartilaginous rod of the second arch segments like the first into three pieces. Of these the uppermost disappears, the middle one, which lies close up to the labyrinth of the ear, becomes the stapes, and the lowest becomes the anterior horn of the hyoid. The stapes forms a close connection with the hammer and the incus. In birds, where there is a single ear-ossicle, the columella, the middle piece of arch I forms, as we have seen, the quadrate, by means of which the lower jaw is joined to the skull. The proximal end of Meckel's cartilage, which in mammals forms the hammer, here gives the articular surface between the lower jaw and the quadrate. The columella is formed from the middle piece of the three into which the cartilage of the second arch segments. It is, therefore, the homologue of the stapes in mammals. The third arch takes a varying share, together with the second, in the formation of the hyoid apparatus.



In this paper Reichert made a distinct advance on the previous workers in the same field—Rathke, Huschke, von Baer, Martin St Ange, Duges. Huschke was indeed the first to suggest that both upper and lower jaws were formed in the first gill-arch. But both von Baer and Rathke[207] held that the upper jaw developed as a special process independent of the lower jaw rudiment, and the actual proof that the upper jaw is a derivative of the first visceral arch seems to have been first supplied by Reichert. His brilliant work on the development of the ear-ossicles founded what we may justly call the classical theory of their homologies. His views were attacked and in some points rectified, but the main homologies he established are even now accepted by many, perhaps the majority of morphologists.

In a paper of 1838 on the comparative embryology of the skull in Amphibia,[208] Reichert added to his results for mammals and birds an account of the fate of the first and second visceral arches in Anura and Urodela.

The first visceral arch, he found, gave in Amphibia practically the same structures as in the higher Vertebrates. Its skeleton segmented, as in mammals and birds, into three parts; the upper part gave rise to the palatine and pterygoid in Anura, but seemed to disappear in Urodeles, where the so-called palatine and pterygoid developed in the mucous membrane of the mouth; the middle part gave, as in birds, the quadrate, which formed a suspensorium for both arches; the lower part, as Meckel's cartilage, formed a foundation for the bones of the lower jaw. Of arch II., the lower part became the horn of the hyoid, the upper part had a varying fate. In some Anura it formed the ossicle of the ear (homologue of the columella of birds and the stapes of mammals), in others it disappeared. In reptiles the upper segment of the second arch formed, as in birds, the columella.

The account of the metamorphoses of the visceral arches in Amphibia forms only a small part of Reichert's memoir of 1838, the chief object of which was to discover the general "typus" of the vertebrate skull, and to follow out its modifications in the different classes. Von Baer had shown that the generalised type appeared most clearly in the early embryo; Reichert therefore sought the archetype of the skull in the developing embryo. He brought to his task the preconceived notion that the skull could be reduced to an assemblage of vertebrae, but he saw that comparative anatomy alone could not effect this reduction; he had recourse, therefore, to embryology, hoping to find in the simplified structure of the embryo clear indications of three primitive cranial vertebrae (p. 121, 1837).

In the head he distinguished two tubes, the upper formed by the dorsal plates, the lower by the ventral or visceral plates. Both of these tubes were derived from the serous or animal layer (cf. von Baer, supra, p. 118). The walls of the lower tube were formed by the visceral processes, within which later the skeleton of the visceral arches developed. The walls of the upper tube formed the bones and muscles of the cranium proper. The facial part of the head was formed by elements from both upper and lower tubes. The dorsal tube showed signs of a division into three cranial vertebrae (Urwirbeln, primitive vertebrae). In mammals and birds, as Reichert had shown in his 1837 paper, the three cranial vertebrae were indicated by transverse furrows on the ventral surface of the still membranous skull (see Fig. 10, p. 148).

Even in mammals and birds, however, the positions of the eye, the ear-labyrinth, and the three visceral arches were the safest guides to the delimitation of the cranial vertebrae (pp. 134-138, 1837). In Amphibia generally there were no definite lines of separation on the skull itself. "At this stage," he writes of the cartilaginous cranium of the frog, "we find no trace of a veritable division into vertebrae in the cartilaginous trough formed by the basis cranii and the side parts. On the contrary, it is quite continuous, as it is also in the higher Vertebrates during the process of chondrification" (p. 44, 1838). The vertebrae in the membranous or cartilaginous skull could be delimited in Amphibia by the help of the eye and the ear-labyrinth, which lie more or less between the first and second, and the second and third vertebrae, but, above all, by the vesicles of the brain.

As in the higher Vertebrates, the visceral arches are associated with the cranial vertebrae as their ventral extensions, being equivalent to the visceral plates which form the ventral portion of the "primitive vertebrae" or primitive segments of the trunk.



If the three cranial vertebrae are not very distinct in the early stages of development when the skull is still membranous or cartilaginous, they become clearly delimited when ossification sets in. Three rings of bone forming three more or less complete vertebrae are the final result of ossification. The composition of these rings is as follows:—

+ -+ Base. Sides. Top. + -+ -+ First vertebra Presphenoid Orbitosphenoids Frontals Second vertebra Basisphenoid Alisphenoids Parietals Third vertebra Basioccipital Exoccipitals Supraoccipital + -+

The other bones of the skull are not included in the vertebrae, and this is in large part due to the fact that the sense capsules are formed separately from the cranium (p. 29, 1838). The ear-labyrinth, it is true, fuses indissolubly with the cranium at a later period, but the bones which develop in its capsule are not for all that integral parts of the primitive cranial vertebrae. This point, it is interesting to note, had already been made by Oken in his Programm (1807). But many of the bones developed in relation to the sense organs can find their place in the generalised embryonic schema or archetype of the vertebrate skull, for they are of very constant occurrence during early development.

Having arrived at a generalised embryonic type for the vertebrate skull, of which the fundamental elements are the three cranial vertebrae and their arches, Reichert goes on to discuss the particular forms under which the skull appears in adult Vertebrates. He accepts in general von Baer's law that the characters of the large groups appear earlier in embryogeny than the characters of the lesser classificatory divisions. "When we observe new and not originally present rudiments in very early embryonic stages, as, for instance, that for the lacrymals, the probability is that they belong to the distinctive development of one of the larger vertebrate groups. From these are to be carefully distinguished such rudiments as arise later during ossification, mostly as ossa intercalaria, in order to give greater strength to the skull in view of the greater development of the brain, etc.; the latter give their individual character to the smaller vertebrate groups, and comprise such bones as the vomer, the Wormian bones, the lowermost turbinal, etc." (p. 63, 1838).

He did not accept the Meckel-Serres law of parallelism. He recognised the great similarity between the unsegmented cartilaginous cranium of Elasmobranchs, and the primordial cranium of the embryos of the higher Vertebrates, but he did not think that the cranium of Elasmobranchs was simply an undeveloped or embryonic stage of the skulls of the higher forms. Rather "do the Holocephala, Plagiostomata, and Cyclostomata appear to us to be lower developmental stages individually differentiated, so that the other fully differentiated Vertebrates cannot easily be referred directly to their type" (p. 152, 1838). The skull of these lower fishes is itself a specialised one; it is an individualised modification of a simple type of skull. And this holds good in general of the skulls of the lower Vertebrates—they are individualised exemplars of a simple general type, not merely unmodified embryonic stages of the greatly differentiated skulls of the higher Vertebrates (p. 250, 1838). Differentiation within the vertebrate phylum is therefore not uniserial, but takes place in several directions. Reichert describes two sorts of modifications of the typical skull—class modifications and functional modifications. The causes of the modifications which characterise classificatory groups are unknown; the second class of modifications occur in response to adaptational requirements.

Reichert's two papers are of considerable importance, and Mueller's remark in his review[209] of them is on the whole justified. "These praiseworthy investigations supply from the realm of embryology new and welcome foundations for comparative anatomy" (p. clxxxvii.).

The development of the skull was, however, more thoroughly worked out by Rathke, and with less theoretical bias, in his classical paper on the adder.[210] This memoir of Rathke's is an exhaustive one and deals with the development of all the principal organ-systems, but particularly of the skeletal and vascular. He confirmed in its essentials Reichert's account of the metamorphoses of the first two visceral arches, describing how the rudiment of the skeleton of the first arch appears as a forked process of the cranial basis, the upper prong developing into the palatine and pterygoid, the lower forming Meckel's cartilage, while the quadrate develops from the angle of the fork. The actual bone of the upper jaw (maxillary) develops outside and separate from the palato-pterygoid bar. The cartilaginous rod supporting the second visceral arch divides into three pieces on each side, of which the lower two form the hyoid, the uppermost the columella. Like Reichert he held the visceral arches to be parts of the visceral plates, containing, however, elements from all three germ-layers—the serous, mucous, and vessel layers.

The first gill-slit, or, as Rathke here prefers to call it, pharyngeal slit, closes completely in snakes and in Urodeles. It forms the Eustachian tube in all other Tetrapoda. As regards the vertebrae, Rathke describes them as being formed in the sheath of the chorda from paired rudiments, each of which sends two branches upwards, and two branches downwards. The two inner pairs of processes coalesce round the chorda, and later form the centrum; the upper outer pair meet above the spinal column; the lower outer pair form ribs. The odontoid process of the axis vertebra is the centrum of the atlas (p. 120). The formation of vertebral rudiments begins close behind the ear-labyrinth, but in front of this the chorda-sheath gives origin to a flat membranous plate which afterwards becomes cartilaginous. This plate reaches forward below the third cerebral vesicle as far as the infundibulum. The notochord ends in this plate, which is the basis cranii, just at the level of the ear-labyrinth. In no Vertebrate does the notochord extend farther forward (p. 122). The basis cranii gives off three trabeculae. The middle one is small and sticks up behind the infundibulum; it is absent in fish and Amphibia, and soon disappears during the development of the higher forms. The lateral trabeculae are long bars which curve round the infundibulum and reach nearly to the front end of the head. Together they are lyre-shaped. The cranial basis and the trabeculae are formed, like the vertebrae, in the sheath of the notochord, and the only differences between the two in the early stage of their development are that the formative mass for the cranial basis is much greater in amount than that for the vertebrae, and that the cranial basis by means of its processes, the trabeculae, reaches well in front of the terminal portion of the notochord (p. 36). The capsule for the ear-labyrinth develops quite independently of the cranial basis and the notochord. It resembles on its first appearance, in form, position, composition, and connections, the ear-capsule of Cyclostomes, and so do the ear-capsules of all embryonic Vertebrates (p. 39). It manifests clearly the embryonic archetype, ... "there exists one single and original plan of formation, as we may suppose, upon which is built the labyrinth of Vertebrates in general" (p. 40). When ossification sets in, the ear-capsule forms three bones, of which two fuse with the supraoccipital and exoccipitals.



During the formation of the ear-capsule the cranial basis develops from a plate to a trench, for in its hinder section the side parts grow up to form the side walls of the brain, in exactly the same way as the processes of the vertebral rudiments grow up to enclose the spinal column (pp. 122, 192). The foundations of the skull are now complete, and ossification gradually sets in. The basioccipital is formed in the posterior part of the basis cranii, and the exoccipitals in the side walls of the trench in continuity with the fundament of the basioccipital (see Fig. 11). The supraoccipital is formed in cartilage above the exoccipitals. The basisphenoid develops, like the basioccipital, in the flat basis cranii, but towards its anterior edge, between the large foramen (h) and the pituitary space (i). It is formed from two centres, each of which is originally a ring round the carotid foramen. The presphenoid develops in isolation between the lateral trabeculae, just behind the point where they fuse. The side parts of the basisphenoid and presphenoid (forming the alisphenoids and the orbitosphenoids respectively) develop in cartilage separately from the cranial basis, not like the exoccipitals in continuity with it. The hinder parts of the trabeculae become enclosed by two processes of the basisphenoid; their front parts remain in a vestigial and cartilaginous state alongside the presphenoid. The frontals and parietals show a peculiar mode of origin in the adder, differing from their origin in other Vertebrates. The frontals develop in continuity with the orbitosphenoids, the parietals in continuity with the alisphenoids, and so have much resemblance with the vertebral neural arches which surround the spinal column (p. 195).

Through Rathke's work the real embryonic archetype of the vertebrate skull was for the first time disclosed. Rathke discussed this archetype and its relation to the vertebral theory of the skull in another paper of the same year (1839), but before going on to this paper, we shall quote from the paper on the adder the following passage, remarkable for the clear way in which the idea of the embryological archetype is expressed. "Whatever differences may appear in the development of Vertebrates, there yet exists for the different classes and orders a universally valid idea (plan, schema, or type) ruling the first formation of their separate parts. This idea must first be worked out, though possibly with modifications, before more special ideas can find play. The result of the latter process, however, is that what was formed by the first idea is not so much hidden as partially or wholly destroyed" (p. 135).

Rathke's general paper on the development of the skull in Vertebrates[211] treats the matter on a broader comparative basis than his paper on the adder, and takes into account all the vertebrate classes, in so far as their development was then known. He here makes the interesting suggestion, later entirely confirmed, that the basis cranii or basilar plate is first laid down as two strips, one on each side of the chorda—the structures now known as parachordals (pp. 6, 27). For this supposition, he thinks, speaks the structure of the skull in Ammocoetes, which in this respect is the simplest of all Vertebrates (pp. 6, 22). In Ammocoetes, as Johannes Mueller had shown, the foundation of the skull is formed by two long cartilaginous bars, between the hinder portions of which the notochord ends. In these Rathke was inclined to see the homologues of his trabeculae, and of the parachordals which he was ready to assume from his embryological observations.

Mueller was, of course, very ready to accept Rathke's opinions on this subject, for he considered that they supported his own theory of the vertebral nature of the skull. After describing in his Handbuch der Physiologie the cartilaginous bands in Ammocoetes and their highly differentiated homologues in the Myxinoids, he writes in the later editions, "Hence we see that in the cranium, as in the spinal column, there are at first developed at the sides of the chorda dorsalis two symmetrical elements, which subsequently coalesce, and may wholly enclose the chorda. Rathke has recently observed, in the embryos of serpents and other animals, before the formation of the proper cranial vertebrae, two symmetrical bands of cartilage, similar to those which I discovered as a persistent structure in Ammocoetes.... At a later period the basis cranii of vertebrate animals contains three parts analogous to the bodies of vertebrae, the most anterior of which, in the majority of animals, is generally small, and its development frequently abortive, whilst in man and mammiferous animals the three are very distinct. These parts are developed by the formation of three distinct points of ossification, one behind the other, in the basilar cartilage."[212]

Rathke was very cautious about accepting the vertebral theory of the skull; he saw that the facts of development were not altogether favourable to the theory, and he gave his adherence with many reservations and saving clauses. His general attitude may be summed up as follows.[213]

The chorda sheath is the common matrix of the vertebrae and of a large part of the skull. The basilar plate and the trabeculae, which are developed from the chorda sheath, give origin to three bones, which might possibly be considered equivalent to vertebral centra—the basioccipital, the basisphenoid, and the Riechbein (ethmoid). The Riechbein develops from the fused ends of the trabeculae. The presphenoid might also be considered as a vertebral body, but it develops independently of the basilar plate and trabeculae.

Now of these bones, the basioccipital is in every way equivalent to a vertebral centrum, for it develops in the basilar plate round the notochord. With the exoccipitals, which arise just like neural arches, it forms a true vertebra. The supraoccipital is an accessory bone developed in relation to bigger brains. The basisphenoid appears in the basilar plate, but in front of the notochord, nor does it arise in exactly the same way as the centrum of a vertebra. The basisphenoid with the alisphenoids, which develop independently in the side walls of the brain, may, however, still be considered as forming a vertebra, though the resemblance is not so great as in the case of the occipital ring. The presphenoid, being long and pointed, is very unlike a vertebral body. The orbitosphenoids develop separately from it. The ethmoid also differs from a vertebra, for it surrounds not the whole nervous axis as the two hinder "vertebrae" do, but only two prolongations of it, the olfactory lobes. In its development and final form it shows no particular resemblance to a vertebra. Its body, the pars perpendicularis (mesethmoid) shows no similarity with a vertebral centrum. Completing the three hinder cranial "vertebrae" and roofing in the brain are the supraoccipital, the parietals and the frontals. The premaxillaries, vomer, and nasals do not belong to the cranial scheme; they are covering bones connected with the ethmoid. So, too, the ear-capsule is not part of the cranial vertebrae, but is rather to be compared to the intercalary bones in the vertebral column of certain fish. Summing up as regards the cranial vertebrae Rathke writes, "We find that the four different groups of bones, consisting of the basioccipital with its intercalary (the supraoccipital), the basisphenoid with its intercalaries (parietals), the presphenoid with its intercalaries (frontals), and the ethmoid with its outgrowths (turbinals and cribriform plate), taking them in order from behind forwards, show an increasing divergence from the plan according to which vertebrae as commonly understood develop, so that the basioccipital shows the greatest resemblance to a vertebra, the ethmoid the least" (p. 30).

In a posthumous volume published in 1861 the same opinion is put forward. "In the head, too," he writes, "some vertebrae can be recognised, although in a more or less modified form. Yet at most only four cranial vertebrae can be assumed, and these differ from ordinary well-developed vertebrae in their manner of formation the more the farther forward they lie."[214]

Rathke was an able and careful critic of the vertebral theory of the skull, but he accepted it in the main. Actual attack on the theory upon embryological grounds was begun by C. Vogt, in his work on the development of Coregonus,[215] and in his paper on the development of Alytes.[216] He described for Coregonus an origin of the skull in the main similar to that established by Rathke for the adder. There was a "nuchal plate" in which the front end of the notochord was imbedded; the notochord ended at the level of the labyrinth; there were two lateral bands, comparable to Rathke's lateral trabeculae; a "facial plate" was also formed, which seems on the whole equivalent to the plate formed by the fused anterior ends of the trabeculae. A little later the cranium formed a complete cartilaginous box surrounding the brain, very similar to the adult cranium of a shark.

In his criticism of the vertebral theory of the skull, Vogt started by defining the vertebra as a ring formed round the chorda. Now since only the occipital segment of the skull is formed actually round the notochord, the parts of the skull lying in front of this cannot themselves be vertebrae, though they may be considered as prolongations of the occipital or nuchal vertebra. "We must regard the nuchal plate as a true vertebra, modified, it is true, in its formation and development by its particular functions. Now, since the notochord ends with the nuchal plate we can no longer regard as vertebrae the parts of the skull that lie beyond, such as the lateral processes of the cranium and the facial plate, for they have no relation with the notochord" (p. 123).

To support this view he adduced the fact that the vertebral divisions (primitive vertebrae) visible in the trunk do not extend into the head. He used precisely the same arguments in his paper on Alytes to destroy the vertebral theory of the skull. We quote the following passage translated by Huxley (1864, p. 295) from this paper. "It has therefore become my distinct persuasion that the occipital vertebra is indeed a true vertebra, but that everything which lies before it is not fashioned upon the vertebrate type at all, and that efforts to interpret it in such a way are vain; that, therefore, if we except that vertebra (occipital) which ends the spinal column anteriorly, there are no cranial vertebrae at all."

L. Agassiz, himself a pupil of Doellinger, in the general part (1844) of his Recherches sur les Poissons fossiles (Neuchatel, 1833-43), repeats in the main his pupil Vogt's criticism of the vertebral theory (vol. i., pp. 125-9).

These arguments of Vogt and Agassiz were not considered by Mueller to dispose of the theory,[217] which maintained a firm hold even upon embryologists. It was still upheld by Reichert, and Koelliker in 1849 showed himself convinced of its general validity.

A useful step in the analysis of the concept "vertebra" was taken by Remak,[218] who showed what a complex affair the formation of vertebrae really is, involving as it does a complete resegmentation (Neugliederung) of the vertebral column, whereby the original vertebral bodies were replaced by the secondary definitive bodies (p. 143). Remak showed, as he thought, that the protovertebral segmentation of the dorsal muscle-plates did not extend into the head, and he denied Reichert's assertion (1837) that the cranial basis in mammals showed transverse grooves delimiting three cranial vertebrae (p. 36). The gill-slits, he considered, could not possibly be regarded as marking the limits of head vertebrae.

In 1858 appeared Huxley's well-known Croonian Lecture, On the Theory of the Vertebrate Skull,[219] in which he stated with great clearness and force the case for the embryological method of determining homologies, and criticised with vigour the vertebral theory of the skull. By this time the two rival methods in morphology had become clearly differentiated, and Huxley was able to contrast them, or at least to show how necessary the new embryological method was as a corrective and a supplement to the older anatomical, or, as he calls it, "gradation" method. Applied to the "Theory of the Skull," the gradation method consists in comparing the parts of the skull and vertebral column in adult animals with respect to their form and connections. "Using the other method, the investigator traces back skull and vertebral column to their earliest embryonic states and determines the identity of parts by their developmental relations" (p. 541). This second method is the final and ultimate. "The study of the gradations of structure presented by a series of living beings may have the utmost value in suggesting homologies, but the study of development alone can finally demonstrate them" (p. 541). As an example of the utility and, indeed, the necessity of applying the embryological method Huxley takes the case of the quadrate bone in birds. This bone had been generally regarded by anatomists as the equivalent of the tympanic of mammals, on account of its connection with the tympanum; but Reichert showed (1837) that the same segment of the first visceral arch developed into the incus in mammals, and into the quadrate in birds, and that therefore the quadrate was homologous with the incus. Similarly, on developmental grounds, the malleus or hammer of mammals is the homologue of the articular of birds, since both are developed from a portion of Meckel's cartilage identical in form and connections in the two groups. The homologies of the bones connected with the jaws in bony fishes had long been a subject of contention among comparative anatomists; Huxley shows from his personal observations how the development of the visceral arches throws light upon these difficulties. The mandibular arch in the developing fish is abruptly angled, as in the embryo of Tetrapoda; the upper prong of it ossifies into the palatine and pterygoid; at the angle is formed the quadrate (jugal, Cuvier), and to the quadrate is articulated the lower jaw, which ossifies round the lower prong or Meckel's cartilage. The scheme of development of the jaws is accordingly similar in fish to what it is in other Vertebrates, and this similarity of development enables Huxley to recognise what are the true homologues of the quadrate, the palatine and the pterygoid in adult bony fish, and to prove that the symplectic and the metapterygoid (tympanal, Cuvier) are bones peculiar to fish. In developing Amphibia Huxley found a suspensorium of hyoid and mandibular arches similar to the hyomandibular of fish.

Tackling his main problem of the unity of plan of the vertebrate skull, Huxley shows, by a careful discussion of the anatomical relationships of the chief bones in typical examples of all vertebrate classes, that there is on the whole unity of plan as regards the osseous skull. This unity of composition can be established, on the gradation method, by considering the connections of the bones of the skull with one another, their relations to the parts of the brain and to the foramina of the principal cranial nerves. The assistance of the embryological method is, however, necessary in determining many points with regard to the bones developed in relation to the visceral arches. But there is a further step to be taken. "Admitting ... that a general unity of plan pervades the organisation of the ossified skull, the important fact remains that many vertebrated animals—all those fishes, in fact, which are known as Elasmobranchii, Marsipobranchii, Pharyngobranchii and Dipnoi have no bony skull at all, at least in the sense in which the words have hitherto been used" (p. 571). The membranous or cartilaginous skull of these fishes shows a general resemblance in its main features to the ossified skull of other Vertebrates; the relations of the ear to the vagus and trigeminal nerves are, for instance, the same in both; the main regions of the cartilaginous skull can be homologised with definite bones or groups of bones in the bony skull; but discrepancies occur. It is again to development that we must turn to discover the true relationship of the cartilaginous to the ossified skull. "The study of the development of the ossified vertebrate skull ... satisfactorily proves that the adult crania of the lower Vertebrata are but special developments[220] of conditions through which the embryonic crania of the highest members of the sub-kingdom pass" (p. 573). It is with the embryonic cranium of higher Vertebrates that the adult skull of the lower fishes must be compared, and the comparison will show a substantial though not a complete agreement between them. Thus, speaking of the development of the frog's skull, Huxley writes:—"If, bearing in mind the changes which are undergone by the palatosuspensorial apparatus, ... we now compare the stages of development of the frog's skull with the persistent conditions of the skull in the Amphioxus, the lamprey, and the shark, we shall discover the model and type of the latter in the former. The skull of the Amphioxus presents a modification of that plan which is exhibited by the frog's skull when its walls are still membranous and the notochord is not yet embedded in cartilage. The skull of the lamprey is readily reducible to the same plan of structure as that which is exhibited by the tadpole when its gills are still external and its blood colourless. And finally, the skull of the shark is at once intelligible when we have studied the cranium in further advanced larvae, or its cartilaginous basis in the adult frog" (p. 577). Development, therefore, proves what comparative anatomy could only foreshadow—the unity of plan of all vertebrate skulls, ossified and unossified alike. "We have thus attained to a theory or general expression of the laws of structure of the skull. All vertebrate skulls are originally alike; in all (save Amphioxus?) the base of the primitive cranium undergoes the mesocephalic flexure, behind which the notochord terminates, while immediately in front of it the pituitary body is developed;[221] in all, the cartilaginous cranium has primarily the same structure—a basal plate enveloping the end of the notochord and sending forth three processes, of which one is short and median, while the other two, the lateral trabeculae, pass on each side of the space on which the pituitary body rests, and unite in front of it; in all, the mandibular arch is primarily attached behind the level of the pituitary space, and the auditory capsules are enveloped by a cartilaginous mass, continuous with the basal plate between them. The amount of further development to which the primary skull may attain varies, and no distinct ossifications at all may take place in it; but when such ossification does occur, the same bones are developed in similar relations to the primitive cartilaginous skull" (p. 578).

In a word, there is a general plan or primordial type which is manifested in the higher forms most clearly in their earliest development—an embryological archetype therefore.

Huxley now goes on to consider the relation of this general plan or type of the skull to the structure and development of the vertebral column. Does the skull in its development show any signs of a composition out of several vertebrae? The vertebral column develops as a segmented structure round the notochord; the skull develops first as an unsegmented plate extending far beyond the notochord. The processes of this basilar plate, the trabeculae, are quite unlike anything in the vertebral column. It is true that when the process of ossification begins, separate bones are differentiated in the basilar plate one in front of the other, giving an appearance of segmentation. The hindmost of these bones, the basioccipital, ossifies round the notochord, quite like a vertebral centrum, and its side parts which form the occipital arch develop in a "remotely similar" way to the neural arches of the vertebrae. The next bone, however, the basisphenoid, develops in front of the notochord, and shows very little analogy with a vertebral body. The analogy is even more far-fetched when applied to the axial bones in front of the basisphenoid. The cranium might indeed be divided upon ossification into a series of segments bearing a more or less remote analogy with vertebrae. "In the process of ossification there is a certain analogy between the spinal column and the cranium, but that analogy becomes weaker and weaker as we proceed towards the anterior end of the skull" (p. 585). The best way to state the facts is to say that both skull and vertebral column start in their development from the same point, but immediately begin to diverge. The clear indications of segmentation which fully ossified adult skulls undoubtedly show are, therefore, secondary, and the vertebral theory of the skull, which was originally based upon the appearance of such fully ossified crania, is on the whole negatived by embryology.

We have now to turn back a few years in order to follow up another line of discovery which had an important bearing upon the theory of the vertebrate skull—the working out of the distinction between membrane and cartilage bones.

As early as 1731, R. Nesbitt,[222] in two lectures delivered to the Royal College of Surgeons, demonstrated that in the human foetus some bones were formed not in cartilage but directly in fibrous tissue, and this observation was confirmed by other human anatomists, particularly by Sharpey at a considerably later date. In 1822 Arendt[223] focussed attention upon the remarkable structure of the skull of the Pike, with its cartilaginous brain-box studded all over with bony plaques, an arrangement which had already attracted the interest of Cuvier and Meckel. K. E. von Baer[224] in 1826 discussed at some length the relation between the bony and the cartilaginous skull in fishes, with particular reference to the sturgeon, coming to the following just conclusion:—"If we consider the fibrous skeleton of Ammocoetes as the first foundation of the skeleton of Vertebrates, we can form a series among the cartilaginous fishes, according as a cartilaginous skeleton penetrates more and more into this fibrous foundation. In the same way the process of ossification supplants the cartilaginous skeleton. So long as the ossifications lie in the skin, as in the sturgeon, they form corneous bones (Hornknochen), but when they lie under the skin, they form true bones, e.g., the bones of the skull in the pike" (p. 374).

Embryologists soon become aware that a similar distinction between a primitive cartilaginous foundation and a secondary overlying ossification of the skull showed itself in the development of all Vertebrates. Duges, in his Recherches sur l'osteologie et la myologie des Batraciens (1834), distinguished between such bones as are formed by direct ossification of the cartilaginous groundwork of the skull, and such as are developed in the periosteal fibrous tissue.

Reichert in 1838[225] noted that several of the skull bones in Amphibia are formed without the intermediary of cartilage, such as the nasals, the maxillaries and the lacrymals. So, too, the frontals and parietals of Teleosts developed independently of the cartilaginous skull, and belonged to the skeletal system of the skin, not to the true vertebral axial skeleton (pp. 215-6). Even more interesting was his discovery, afterwards confirmed by Hertwig,[226] that in the newt several bones connected with the palate were formed in the mucous membrane of the mouth by the fusion of a number of little conical teeth (p. 97). Certain of these bones he considered to be the substitutes, not the equivalents, of the palatine and pterygoid of other Vertebrates, which are formed from the upper part of the first visceral arch, a part missing in the newt (p. 100). Owing to the difference of development he would not homologise these bones in the newt with the palatine and pterygoid of other Vertebrates. He recognised also that the bone now known as the parasphenoid was developed in the frog in the mucous membrane of the mouth, and had originally no connection with the cranial basis (p. 34). Rathke in 1839 also allowed the distinction between cartilage and membrane bone, but laid no stress upon it (Entw. d. Natter., p. 197).

Jacobson in 1842[227] introduced the useful term, "primordial cranium," for the primitive cartilaginous foundation of the skull, and drew a sharp distinction between cartilage bones and membrane bones.

In his Recherches sur les Poissons fossiles,[228] L. Agassiz used Vogt's work on the development of Coregonus to establish a classification of the bones of the skull in fish, a classification which had the merit of drawing a sharp distinction between the cartilaginous groundwork and the "protective plates" of the fish's skull. He recognised that the protective plates developed in a different way from the other bones of the skull. "We must distinguish," he writes, "two kinds of ossification; one which tends to transform the primitive parts of the embryonic cranium directly into bone, and another which leads to the deposition of protective plates round this core, which develop not only upon the upper surface, as has hitherto been supposed, but also on the lateral walls and on the lower surface of the cranium" (p. 112). In the skull of all fish there are three elements—(1) the cartilaginous base, including the nuchal plate, the trabeculae and the facial plate, together with the auditory capsules; (2) the cartilaginous cerebral envelope; (3) the bony protective plates (absent in Elasmobranchs). The bones developed in relation to these cranial elements can be classified as follows:—(1) the basioccipital, exoccipitals (paroccipitals?), supraoccipital and "petrous" (rocher), developed from the nuchal plate; the ali- and orbito-sphenoids developed from the trabeculae; the "cranial ethmoid"[229] developed from the facial plate; (2) the parietals, frontals and nasals formed from the "superior" protective plate; the "anterior" and "posterior" frontals and the temporal, from the "lateral" plates; the body of the sphenoid and the vomer from the "inferior" plates. The other element, the cartilaginous brain-box, does not ossify, and tends to become absorbed (p. 124).

In 1849 Koelliker published a paper[230] dealing with the morphological significance of the distinction between membrane and cartilage bones, and in 1850[231] he defended his views against the criticisms of Reichert[232] in a further note entitled Die Theorie des Primordialschaedels festgehalten. It is convenient to consider these papers together. Koelliker held that there was (1) a histological and (2) a morphological difference between the two categories of bones. The histological development of the two kinds was different, but this difference was not sufficient to establish a morphological distinction between them, a distinction in their anatomical Bedeutung. The true morphological distinction between them was their development in different skeleton-forming layers. Membrane bones were developed in fibrous tissue lying between the skin and the deep layer which formed the primordial cranium, and it was this formation in a separate layer that gave them a different morphological significance from the bones formed directly in the deep layer. Koelliker's distinction, therefore, was between the bones formed in the primordial cartilaginous cranium on the one hand, and the superficial ossifications in fibrous tissue on the other hand. The cartilaginous cranium in Koelliker's opinion was formed upon the vertebral type, and the membrane bones were accessory. This, at least, was his opinion in 1849. In 1850, after Stannius had shown that membrane bones occurred as integral parts of the vertebrae in certain fish, he modified his view of the membrane bones, and admitted them, at least in some cases, as constituents of the cranial vertebrae.

On this morphological distinction of membrane and cartilage bones future comparative osteology was to be based:—

"My sole aim is to state again the principle upon which comparative osteology is to be based and extended, and this is that first place should be assigned to anatomical considerations, and among these to the manner of origin of the whole bone in relation to the skeleton-forming layers" (1850, p. 290).

The homologies established by this new principle might run counter to the homologies indicated by the study of adult structure. "Thus, for instance, although the lower jaw in position, function, form and shape, appears to be the same bone throughout, yet it must be admitted that it shows a difference in the different classes. In Mammals and Man it is an entirely secondary bone (an extremity according to Reichert), in Birds, Amphibia and Fishes only partially so, for its articular belongs to Meckel's cartilage and is accordingly analogous to a rib; indeed, in the Plagiostomes, etc., the whole lower jaw along with the articular is a persistent Meckel's cartilage" (p. 290, 1850).

So, too, the supraoccipital in man cannot be fully homologised with the supraoccipital of many mammals, for its upper half arises at first in isolation as a secondary bone (p. 290).

Reichert objected to the distinction drawn by Koelliker, and denied that there was either a histological or a morphological difference between membrane and cartilage bones. It was shown a few years later by H. Mueller[233] that there was in truth no essential difference in histological development between the two categories of bone, that the cartilage cells were replaced by bone cells identical with those taking part in the formation of membrane bones. The morphological distinction continued however to be recognised, particularly by the embryologists. Rathke in his volume of 1861[234] classified the bones of the skull according to their origin from the primordial cranium or from the overlying fibrous layer, distinguishing as membrane bones, the parietals, frontals, nasals, lachrymals, maxillaries and premaxillaries, jugals, tympanic, parts of the "temporal," vomer, part of the supraoccipitals in some mammals, and the mandible (with the exception of the articular in such as have a quadrate bone). Huxley was also inclined in 1864[235] to recognise the distinction, but he writes with some reserve:—"Is there a clear line of demarcation between membrane bones and cartilage bones? Are certain bones always developed primarily from cartilage, while certain others as constantly originate in membrane? And further, if a membrane bone is found in the position ordinarily occupied by a cartilage bone, is it to be regarded merely as the analogue and not as the homologue of the latter?" (p. 296).

We may note here that many comparative anatomists of the period were quite ready to decide Huxley's last question in a sense favourable to the older, purely anatomical, view of homology. Owen, for instance, held that difference of development did not disturb homologies established by form and connections. "Parts are homologous," he writes, "in the sense in which the term is used in this work, which are not always similarly developed: thus the 'pars occipitalis stricte dicta,' etc., of Soemmering is the special homologue of the supraoccipital bone of the cod, although it is developed out of pre-existing cartilage in the fish and out of aponeurotic membrane in the human subject."[236] Similarly he pointed to the diversities of development of the vertebral centrum in the different vertebrate classes as proof that development could not always be relied upon in deciding homologies (p. 89). But he could not deny that the archetype was better shown in the embryo than in the adult (supra, p. 108).

J. V. Carus[237] likewise stood firm for the older method of determining homologies by comparison of adult structure. "We can regard as homologous," he writes, "only those parts which in the fully formed animal possess a like position and show the same topographical relations to the neighbouring parts" (p. 389). Parts homologous in this sense might develop in different ways, but no great importance was to be attached to such a circumstance. Membrane and cartilage bones developed in practically the same way, from the same skeleton-forming layer, and no morphological significance attached to their distinction (pp. 227, 457). Embryology was of considerable value in helping to determine homologies, but the evidence that it supplied was contributory, not conclusive. Perhaps the greatest service which the study of development rendered was to disentangle, by a comparison of the earliest embryos, the generalised type (p. 389).

We have now traced, by our historical study of the theory of the skull, the gradual evolution of the tendency to find in development the surest guide to determining homologies. We have seen how the embryological "type" came to be substituted, in whole or in part, for the anatomical "type" derived from the study of adult structure. But we have had to do only with a modification, not with a transformation, of the criterion of homology recognised by the anatomists. Homology is still determined by position, by connections, in the embryo as in the adult. "Similarity of development" has become the criterion of homology in the eyes of the embryologist, but "similarity of development" means, not identity of histological differentiation, but similarity of connections throughout the course of development. For the purposes of morphology, development has to be considered as an orderly sequence of successive forms, not in its real nature as a process essentially continuous. Morphology has to replace the living continuity by a kinematographic succession of stages. Since it is the earliest of these stages that manifest the simplest and most generalised structural relations of the parts, it is in the earlier stages that homologies can be most easily determined. But these homologies are still determined solely by the relative positions and connections of the parts, just as homologies are determined in the last of all the stages of development, the adult state. And since the generalised type is shown most clearly in the earliest stages and tends to become obscured by later differentiation, homologies observed in embryonic life are to be upheld even if the relations in adult life seem to indicate different interpretations.

[183] See review by Cuvier, Mem. Mus. Hist, nat., iii., pp. 82-97, 1817.

[184] Mem. Savans etrangers, vi. Extract in Ann. Sci. nat. (2) i. (Zool.), pp. 366-72, 1834.

[185] Recherches sur la generation des Mammiferes, 1834. Embryogenie comparee, 1837.

[186] "Kiemen bey Saeugthieren," Isis, pp. 747-9, 1825.

[187] "Kiemen bey Voegeln," Isis, pp. 1100-1, 1825.

[188] "Ueber die Kiemenbogen und Kiemengefaesse beym bebrueteten Huehnchen," Isis, xx., pp. 401-3, 1827. (Read in Sept. 1826 to the Versammlung der deutschen Naturforscher und Aerzte, then recently founded by Oken).

[189] Isis, pp. 160-4, Pl. II., 1828.

[190] "Ueber die Kiemen und Kiemengefaesse in den Embryonen der Wirbelthiere," Meckel's Archiv for 1827, pp. 556-68. Also in Ann. Sci. nat., xv., pp. 266-80, 280-4, 1828.

[191] Meckel's Archiv, vi., pp. 1-47, 1832.

[192] Untersuchungen ueber die Bildung und Entwickelung der Fluss-Krebses, Leipzig, folio, 1829. Preliminary notice in Isis, pp. 1093-1100, 1825.

[193] "Untersuchungen ueber die Bildung und Entwickelung der Wasser-Assel.," Abh. z. Bild. u. Entwick.-Gesch., i., pp. 1-20, 1832. Translated in Ann. Sci. nat. (2), ii., (Zool.), pp. 139-57, 1834.

[194] Koelliker, Entwickelungsgeschichte, 2nd ed., p. 17, Leipzig, 1879.

[195] Handbuch der Entwickelungsgeschichte des Menschen und ... der Saeugethiere und Voegel, Berlin, 1835.

[196] Embryogenie comparee, 1837; Histoire generale du developpement des corps organises, 1847-49.

[197] Entwickelungsgeschichte des Kaninchen-Eies, Braunschweig, 1842; Entwickelungsgeschichte des Hunde-Eies, Braunschweig, 1845; Entwickelungsgeschichte des Meerschweinchens, Giessen, 1852; Entwickelungsgeschichte des Rehes, Giessen, 1854.

[198] "It is the role of embryology, as my great teacher says, to form the court of appeal for comparative anatomy, and it is from embryology particularly, which has in the last decades provided such signal instances of the unravelling of obscure problems, that we have to expect a definite clearing up of the problems relating to the development of the head."—Mueller's Archiv, p. 121, 1837.

[199] Anat.-phil. Unters. ue. d. Kiemenapparat u. d. Zungenbein, Riga and Dorpat, 1832.

[200] "Bildungs- und Entwickelungs-geschichte des Blennius viviparus," Abhandl. z. Bild. u. Entwick.-Gesch. des Menschen u. der Thiere, ii., pp. 1-68, Leipzig, 1833.

[201] Von den Ur-Theilen des Knochen und Schalen-Gerustes, Leipzig, 1828.

[202] Kiemenapparat, pp. 107-118.

[203] Vergleichende Anatomie der Myxinoiden. Part I. (Osteology and Myology). (Abh. koenigl. Akad. Wiss. Berlin, for 1834, pp. 65-340, 9 pls., 1836.) Also separately.

[204] "Ueber die Visceralbogen der Wirbelthiere in Allgemeinen und deren Metamorphosen bei den Voegeln und Saeugethiere," Mueller's Archiv, pp. 120-222, 1837.

[205] Handbuch d. menschl. Anatomie, iv., p. 47.

[206] This was shown by Serres (Ann. Sci. nat., xi., p. 54 f.n., 1827), who found in a human embryo a long cartilaginous piece extending from the ear-ossicles to the inside of the lower jaw, and suggested that it was the foundation of the permanent mandible.

[207] Abhandl., i., p. 102, 1832; ii., p. 25, 1833. (Blennius paper).

[208] Vergleichende Entwickelungsgeschichte des Kopfes der nackten Amphibien, Koenigsberg, quarto, 276 pp., 1838.

[209] Mueller's Archiv for 1838.

[210] Entwickelungsgeschichte der Natter, Koenigsberg, 1839.

[211] Bemerkungen ueber die Entwickelung des Schaedels der Wirbelthiere, Koenigsberg, 1839.

[212] Handbuch der Physiologie des Menschen, Koblenz, 1835; Eng. trans. by W. Baly, ii., p. 1615, 1838.

[213] For a full statement of Rathke's conclusions, see the translation given by Huxley in Lectures on the Elements of Comparative Anatomy, London, 1864.

[214] Entwickelungsgeschichte der Wirbelthiere, p. 142, 1861.

[215] Embryologie des Salmones. A separate volume of L. Agassiz's Histoire naturelle des Poissons d'Eau douce de l'Europe centrale, Neuchatel, 1842.

[216] Untersuchungen ueber die Entwickelungsgeschichte der Gebuertshelferkroete, Solothurn, 1842.

[217] Mueller's Archiv for 1843, p. ccxlviii.

[218] Untersuchtingen ueber die Entwickelung der Wirbelthiere, Berlin, 1850-55.

[219] Delivered 17th June 1858. Reprinted in The Scientific Memoirs of T. H. Huxley, edited by M. Foster and E. Ray Lankester, vol. i., pp. 538-606 (1898).

[220] Cf. Reichert, supra, p. 149.

[221] The origin of the pituitary body from the roof of the mouth was first described by Rathke (1839).

[222] Human Osteogeny explained in two Lectures, London, 1736.

[223] De capitis ossei Esocis lucii structura singulari. Dissert. inaug. Regiomonti, 1822.

[224] "Ueber das aeussere und innere Skelet," Meckel's Archiv, pp. 327-76, 1826.

[225] Vergl. Entwick. d. Kopfes d. nackten Amphibien (p. 186).

[226] Arch. f. mikr. Anat., xi., Suppl., 1874.

[227] "Om Primordial-Craniet," Foerhandlingar Skand. Naturf. Moele, Stockholm, 1842.

[228] Vol. I., General part, pub. 1844.

[229] Entosphenoid, Owen.

[230] Zweiter Bericht zootom. Anstalt zu Wuerzburg, 1849.

[231] Zeits. f. wiss. Zool., ii., pp. 281-91.

[232] Mueller's Archiv for 1849, pp. 443-515.

[233] Zeits. f. wiss Zool., ix., 1858.

[234] Entw. d. Wirbelthiere, pp. 139-40, 1861.

[235] Lectures on the Elements of Comparative Anatomy.

[236] On the Archetype of the Vertebrate Skeleton, p. 5, 1848.

[237] System der thierischen Morphologie, Leipzig, 1853.



CHAPTER XI

THE CELL-THEORY.

With the founding of the cell-theory by Schwann in 1839 an important step was taken in the analysis of the degrees of composition of the animal body. Aristotle had distinguished three—the unorganised material, itself compounded of the four primitive elements, earth and water, air and fire, the homogeneous parts or tissues and the heterogeneous parts or organs, and this conception was retained with little change even to the days of Cuvier and von Baer. Those of the old anatomists who speculated on the relations of organic elements to one another were dominated by Aristotle's simple and profound classification, and proposed schemes which differed from his only in detail. Bichat enlarged and deepened the concept of tissue, but the degree of composition below this was for him, as for all anatomists of his time, a fibrous or pulpy "cellulosity," living, indeed, but showing no uniform and elemental structure. It was Schwann's merit to interpose between the tissue and the mere unorganised material a new element of structure, the cell. And, as it happened, a few years before Schwann published his cell-theory, Dujardin hinted at another degree of composition which was later to take its place between the cell and the chemical elements—sarcode or protoplasm.

As is well known, the concept of the cell arose first in botany. Robert Hooke discovered cells in cork and pith in 1667, and his discovery was followed up by Grew and Malpighi in 1671, and by Leeuenhoek in 1695. But they did not conceive the cell as a living, independent, structural unit. They were interested in the physiology of the plant as a whole, how it lived and nourished itself, and they studied cells and sieve-tubes, wood fibres and tracheae with a view rather to finding out their functions and their significance for the life of the plant than to discovering the minutiae of their structure. The same attitude was taken up by the few botanists who in the 18th century paid any heed to the microscopical anatomy of plants. For C. F. Wolff,[238] the formation of cells was a result of the secretion of drops of sap in the fundamental substance of the plant, this substance remaining as cell-walls when cell-formation was completed—no idea here of cells as units of structure.

In the early 19th century, interest in plant anatomy revived somewhat, and much work was done by Treviranus, Mirbel, Moldenhawer, Meyen and von Mohl.[239] As a result of their work the fact was established that the tissues of plants are composed of elements which can, with few exceptions, be reduced to one simple fundamental form—the spherical closed cell. Thus the vessels of plants are formed by coalescence of cells, fibres by the elongation of cells and the thickening and toughening of their walls. At this time, interest was concentrated on the cell-wall, to the almost total neglect of the cell-contents; the "matured framework" of plant cells, to use Sach's convenient phrase, was the chief, almost the sole, object of study. And it was natural enough that the mere architecture of the plant should monopolise interest, that the composition of the tissues out of the cells, and the fitting together of the tissues to form the plant should awaken and hold the curiosity of the investigator; even the modifications of the cell-walls themselves, their rings and spiral thickenings and pits, offered a fascinating field of enquiry.

The idea that the cell-contents might show a characteristic and individual structure had hardly dawned upon botanists when Schleiden published his famous paper, Beitraege zur Phytogenesis.[240] Schleiden's theme in this paper is the origin and development of the plant cell, a subject then very obscure, in spite of pioneer work by Mirbel. A few years before, Robert Brown had called attention to the presence in the epidermal cells of orchids and other plants of a characteristic spot which he called the areola or nucleus.[241] Schleiden saw the importance of this discovery, confirmed the constant presence of the nucleus in young cells, and held it to be an elementary organ of the cell. He named it the cytoblast because, in his opinion, it formed the cell. It was embedded in a peculiar gummy substance, the cytoblastem, which formed a lining to the cellulose cell-wall. Within the nucleus there was often a small dark spot or sphere—the nucleolus. The nucleus, Schleiden thought, originated as a minute granule in the cytoblastem which gradually increased in size, becoming first a nucleolus (Kernchen), and then, by further condensation of matter round it, a nucleus. Several nuclei might be formed in this way in a single cell. New cells took their origin directly from a full-grown nucleus, in a peculiar way which Schleiden describes as follows:—"As soon as the cytoblasts have reached their full size a delicate transparent vesicle arises on their surface; this is the young cell, which at first takes the shape of a very flat segment of a sphere, of which the plane surface is formed by the cytoblast, the convex side by the young cell itself, which lies upon the cytoblast like a watch-glass on a watch" (p. 145). The young cells increase in size and fill up the cavity of the old cell, which is in time resorbed. Cell-development always takes place within existing cells, and either one or many new cells may be formed within the mother-cell. Schleiden's views on cell-formation were drawn from some rather imperfect observations on the embryo-sac and pollen-tube, but he extended his theory to cell-formation in general. Though wrong in almost all respects the theory had at least the merit of fixing attention upon the really important constituents of the cell, the nucleus and the cell-plasma. To Schleiden, too, we owe the conception of the cell as a more or less independent living unity, whose life is not entirely identified with the life of the plant as a whole. "Each cell," he writes, "carries on a double life; one a quite independent and self-contained life, the other a dependent life in so far as the cell has become an integral part of the plant" (p. 138).

So long as the definition of the plant cell embraced little more than the hardened cell-wall it was little wonder that "cells" in this sense were not recognised in animal tissues, except in a few exceptional cases—as in the notochord by Johannes Mueller.[242] Careful observation of animal tissues discovered in some cases the existence of discontinuous units of structure, but these were not, as a rule, recognised before 1838 as analogous to plant cells. Von Baer, for example, observed that the young chick embryo was composed partly of an albuminous mass and partly of Kuegelchen or little globules suspended in it (Entwickelungsgeschichte, i., pp. 19, 144). Since such Kuegelchen disposed in a row formed the notochord (i., p. 145) it seems probable that his Kuegelchen were really cells. Similarly A. de Quatrefages[243] in 1834 saw and figured segmentation spheres in the developing egg of Limnaea, but he called them globules and did not recognise their analogy with the cells of plants. According to M'Kendrick,[244] Fontana, so far back as 1781,[245] described cells with nuclei in various tissues, and used acids and alkalis to bring out their structure more clearly. But it was not till 1836-7-8 that a fairly widespread occurrence of cells in animal tissues was recognised. The pioneer in this seems to have been Purkinje, who described cells in the choroidal plexus in 1836,[246] and compared gland cells with the cells of plants in 1837.[247] Henle in 1837[248] and 1838[249] described various kinds of epithelial tissue, distinguishing them according to the kind of cell composing them; he also discovered the mode of growth of stratified epithelium. Valentin[250] appears to have seen cells in cartilage and epithelium even before Henle, and to have observed cells in the blastoderm of the chick. In his report on the progress of anatomy during 1838 Johannes Mueller was able to refer to quite a number of papers dealing with the occurrence of cells in animal tissues. In addition to those already noted, he mentions work by Breschet and Gluge on the cells of the umbilical cord, by Dumortier on the cells in the liver of molluscs, by Remak and by Purkinje on nerve cells, by Donne on the cells of the conjuctiva, cornea and lens. He reports, too, that Turpin had compared the epithelial cells of the vagina with the cell-tissue of plants. Mueller himself had not only recognised the cellular nature of the notochord, but had observed the cells of the vitreous humour, fat cells and pigment cells, and even the nuclei of cartilage cells. From Schwann (1839) we learn that C. H. Schults had followed back the corpuscles of the blood to their original state of nucleated cells, and that Werneck had recognised cells in the embryonic lens. A preliminary notice of Schwann's own work appeared in 1838 (Froriep's Notizen, No. 91, 1838), the full memoir in 1839, under the title Mikroskopische Untersuchungen ueber die Uebereinstimmung in der Struktur und dem Wachstume der Tiere und Pflanzen.[251]

Theodor Schwann was a pupil of Johannes Mueller, and we know that Mueller took much interest in the new histology. It is probably to his influence that we owe Schwann's brilliant work on the cell, which appeared just after Schwann left Berlin for Loewen. Schwann was himself, as his later work showed, more a physiologist than a morphologist; he did quite fundamental work on enzymes, discovering and isolating the pepsin of the gastric juice; he proved that yeast was not an inorganic precipitate but a mass of living cells; he carried out experiments directed to show that spontaneous generation does not occur. We shall see in his treatment of the cell-theory clear indications of his physiological turn of mind. Schwann was only twenty-nine when his master-work appeared, and the book is clearly the work of a young man. It has the clear structure, the logical finish, which the energy of youth imparts to its chosen work. So the work of Rathke's prime, the Anatomische-philosophische Untersuchungen of 1832 shows more vigour and a more reasoned structure than his later papers. Schwann's book is indeed a model of construction and cumulative argument, and even for this reason alone justly deserves to rank as a classic.

The first section of his book is devoted to a detailed study of the structure and development of cartilage cells and of the cells of the notochord, and to a comparison of these with plant cells. He accepts Schleiden's account of the origin and development of nuclei and cells as a standard of comparison; and he seeks to show that nucleus and nucleolus, cell-wall and cell-contents, show the same relations and behave in the same manner in these two types of animal cells as in the plant-cells studied by Schleiden. The types of cell which he chose for this comparison are the most plant-like of all animal cells, and he was even able to point to a thickening of the cell-wall in certain cartilage cells, analogous to the thickening which plays so important a part in the outward modification of plant-cells. The analogy indeed in structure and development between chorda and cartilage cells and the cells of plants seemed to him complete. The substance of the notochord consisted of polyhedral cells having attached to their wall an oval disc similar in all respects to the nucleus of the plant-cell, and like it containing one or more nucleoli. Inside the mother-cell were to be found young developing cells of spherical shape, lacking however a nucleus. Cartilage was even more like plant tissue. It was composed of cells, each with its cell membrane. The cells lay close to one another, separated only by their thickened cell-wall and the intercellular matrix, showing thus even the general appearance of the cellular tissue of plants. They contained a nucleus with one or two nucleoli, and the nucleus was often resorbed, as in plants, when the cell reached its full development. Other nuclei were in many cases present in the cell, round which young cells could be seen to develop, in exactly the same manner as in plants. These nuclei had accordingly the same significance as the nuclei of plants, and deserved the same name of cytoblasts or cell-generators. The true nucleus of the cartilage cell was probably in the same way the original generator of the mother-cell.

Having proved the identity in structure and function of the cells of these selected tissues with the cells of plants, as conceived by Schleiden, Schwann had still to show that the generality of animal tissues consisted either in their adult or in their embryonic state of similar cells. This demonstration occupies the second and longest section of his book.

His method is throughout genetic; he seeks to show, not so much that all animal tissues are actually in their finished state composed of cells and modifications of cells, as that all tissues, even the most complex, are developed from cells analogous in structure and growth with the cells of plants.

All animals develop from an ovum; it was his first task to discover whether the ovum was or was not a cell. It happened that, some years before Schwann wrote, a good deal of work had been done on the minute structure of the ovum, particularly by Purkinje and von Baer. Purkinje in 1825[252] discovered and described in the unfertilised egg of the fowl a small vesicle containing granular matter, which he named the Keimblaeschen or germinal vesicle. It disappeared in the fertilised egg. As early as 1791 Poli had seen the germinal vesicle in the eggs of molluscs, but the first adequate account was given by Purkinje. In 1827[253] von Baer discovered the true ova of mammals and cleared up a point which had been a stumbling block ever since the days of von Graaf, who had described as the ova the follicles now bearing his name.[254] Even von Graaf had noticed that the early uterine eggs were smaller than the supposed ovarian eggs; Prevost and Dumas[255] had observed the presence in the Graafian follicle of a minute spherical body, which, however, they hesitated to call the ovum; it was left to von Baer to elucidate the structure of the follicle and to prove that this small sphere was indeed the mammalian ovum. His discovery was confirmed by Sharpey and by Allen Thomson. Von Baer found the germinal vesicle in the eggs of frogs, snakes, molluscs, and worms, but not in the mammalian ovum; he considered the whole mammalian ovum to be the equivalent of the germinal vesicle of birds—a comparison rightly questioned by Purkinje (1834). In 1834 Coste[256] discovered in the ovum of the rabbit a vesicle which he considered to be the germinal vesicle of Purkinje; he observed that it disappeared after fertilisation. Independently of Coste, and very little time after him, Wharton Jones[257] found the germinal vesicle in the mammalian ovum. Valentin in 1835,[258] Wagner in 1836,[259] and Krause in 1837,[260] added considerably to the existing knowledge of the structure of the ovum. Wagner in his Prodromus called attention to the widespread occurrence, within the germinal vesicle of a darker speck which he called the Keimfleck or germinal spot, known sometimes as Wagner's spot. He recognised the Keimfleck in the ova of many classes of animals from mammals to polyps. Frequently more than one Keimfleck occurred.

Schwann had therefore a good deal of exact knowledge to go upon in discussing the significance of the ovum for the cell-theory. There were two possible interpretations. Either the ovum was a cell and the germinal vesicle its nucleus, or else the germinal vesicle was itself a cell within the larger cell of the ovum and the germinal spot was its nucleus. Schwann had some difficulty in deciding which of these views to adopt, but he finally inclined to the view that the ovum is a cell and the germinal vesicle its nucleus, basing his opinion largely upon observations by Wagner which tended to prove that the germinal vesicle was formed first and the ovum subsequently formed round it. But the ovum was not, in Schwann's view, a simple cell, for within it were contained yolk-granules, one set apparently containing a nucleus, the others not. Even the second set, those composing the yellow yolk, were considered by Schwann to deserve the name of cells, because, although a nucleus could not be observed in them, they had a definite membrane, distinct from their contents—a conception of the cell obviously dating from the earliest botanical notions of cells as little sacs. The yolk cells were not mere dead food material but living units which took part in the subsequent development of the egg. The relation between the unfertilised egg and the blastoderm which arises from it is not made altogether clear by Schwann. According to his account the cells of the blastoderm are formed actually in the ovum. Round the nucleus of the egg appears a Niederschlag or precipitate which is the rudiment of the blastoderm (p. 68). When the egg leaves the ovary the nucleus disappears, leaving behind it this rudiment of the blastoderm, which rapidly grows and increases in size. The blastoderm of the chick before incubation is found to be composed of spherical anucleate bodies which Schwann considers to be cells, because they almost certainly develop into the cells of the incubated blastoderm, which are clearly recognisable as such after eight hours' incubation. The serous and mucous layers can be distinguished after sixteen hours' incubation, and it is found that the cells of the serous layer contain definite nuclei, though such seem to be absent in the cells of the mucous layer. Between the two layers other cells are formed belonging to the vessel layer, which is, however, in Schwann's opinion not a very definitely individualised layer.

Schwann's next step is a detailed demonstration of the origin of each tissue from simple cells such as those composing the incubated blastoderm.

"The foregoing investigation has taught us that the whole ovum shows nothing but a continual formation and differentiation of cells, from the moment of its appearance up to the time when, through the development of the serous and mucous layers of the blastoderm, the foundation is given for all the tissues subsequently appearing: we have found this common parent of all tissues itself to consist of cells; our next task must be to demonstrate not only in this general way that tissues originate from cells, but also that the special formative mass of each tissue is composed of cells, and that all tissues are either constituted by simple cells or by one or other of the manifold kinds of modified cells" (p. 71). Five classes of tissue can be distinguished, according to the extent and manner of the modifications which the cells composing them have undergone. There are first of all independent and isolated cells, such as the corpuscles of the blood and lymph, not forming a coherent tissue in the ordinary sense. Next there are the assemblages of cells lying in contiguity with one another, but not in any way fused; examples of this class are the epidermal tissues and the lens of the eye. In the third class come tissues the cells of which have fused by their walls, but whose cell-cavities are not in continuity, such as osseous tissue and cartilage. In the tissues of the fourth class, comprising the most highly specialised of all, not only are the cell-walls continuous but also the cell-cavities; to this class belong muscle, nerve and capillary vessels. A fifth class, of rather a special nature, includes the fibrous tissues of all kinds. This is the first classification of tissues upon a cellular basis, and it marks the foundation of a new histology which took the place of the "general anatomy" of Bichat. The exhaustive account which Schwann gives of the structure and development of the tissues in this section of his book constitutes the first systematic treatise on histology in the modern sense, and it is still worth reading, in spite of many errors in detail.

Schwann found it easy to demonstrate the cellular nature of the tissues of his first three classes. With the other two classes he had more difficulty. Fibres of all kinds, he considered, arose by an elongation of cells, which afterwards split longitudinally into long strips, forming as the case might be white or elastic fibrous tissue. Muscle-fibres and nerve-fibres were formed in a totally different way, by coalescence of cells; each separate muscle-fibre and nerve-fibre was thus a compound cell. Capillaries, Schwann held, were formed by cells hollowed out like drain-pipes, and set end to end—a mistaken view soon corrected by Vogt (Embryologie des Salmones, p. 206, 1842).

In this detail part of his book Schwann accumulates material for a general theory of the cell which he develops in the third and last section. Taking up the physiological or dynamical standpoint, he points out that one process is common to all growth and development of tissues both in animals and plants, namely, the formation of cells, a process which he conceives to take place in the following manner. There is, first of all, a structureless substance, the cytoblastem, the matrix in which all cells originate. The cytoblastem may be either inside the cells, or, more usually, in the spaces between them. It is not a substance of definite chemical and physical properties, for the matrix of cartilage and the plasma of the blood alike come within the definition. It has largely the significance of food material for the developing cells. In plants, according to Schleiden, cells are never formed in the intercellular substance—the cytoblastem is within the cells; but extracellular cell formation seems to be the general rule in animals. An intracellular formation of cells occurs only in the ovum, in cartilage cells and chorda cells and in a few others, and even there it is not the exclusive method of formation; a formation of cells within cells never occurs in muscles and nerves, nor in fibrous tissue (p. 204). In the cytoblastem granules appear, which gradually increase in size and take on the characteristic shape of nuclei; round each of these a young cell is formed. Sometimes the young cells appear to have no nuclei, as in the intracellular brood of chorda cells, but, as a rule, a nucleus is clearly visible. The nucleus is indeed the most characteristic constituent of the cell. "The most important and most constant criterion of the existence of a cell is the presence or absence of the nucleus," writes Schwann near the beginning of his book (p. 43).