EMBRYOLOGY. The word embryo is derived from the Gr. ἔμβρυον, which signified the fruit of the womb before birth. In its strict sense, therefore, embryology is the study of the intrauterine young or embryo, and can only be pursued in those animals in which the offspring are retained in the uterus of the mother until they have acquired, or nearly acquired, the form of the parent. As a matter of fact, however, the word has a much wider application than would be gathered from its derivation. All animals above the Protozoa undergo at the beginning of their existence rapid growth and considerable changes of form and structure. During these changes, which constitute the development of the animal, the young organism may be incapable of leading a free life and obtaining its own food. In such cases it is either contained in the body of the parent or it is protruded and lies quiescent within the egg membranes; or it may be capable of leading an independent life, possessing in a functional condition all the organs necessary for the maintenance of its existence. In the former case the young organism is called an embryo,[1] in the latter a larva. It might thus be concluded that embryology would exclude the study of larvae, in which the whole or the greater part of the development takes place outside the parent and outside the egg. But this is not the case; embryology includes not only a study of embryos as just defined, but also a study of larvae. In this way the scope of the subject is still further widened. As long as embryology confines its attention to embryos, it is easy to fix its limits, at any rate in the higher animals. The domain of embryology ceases in the case of viviparous animals at birth, in the case of oviparous animals at hatching; it ceases as soon as the young form acquires the power of existing when separated from the parent, or when removed from the protection of the egg membranes. But as soon as post-embryonic developmental changes are admitted within the scope of the subject, it becomes on close consideration difficult to limit its range. It must include all the developmental processes which take place as a result of sexual reproduction. A man at birth, when he ceases to be an embryo, has still many changes besides those of simple growth to pass through. The same remark applies to a young frog at the metamorphosis. A chick even, which can run about and feed almost immediately after hatching, possesses a plumage very different from that of the full-grown bird; a starfish at the metamorphosis is in many of its features quite different from the form with which we are familiar. It might be attempted to meet this difficulty by limiting embryology to a study of all those changes which occur in the organism before the attainment of the adult state. But this merely shifts the difficulty to another quarter, and makes it necessary to define what is meant by the adult state. At first sight this may seem easy, and no doubt it is not difficult when man and the higher animals alone are in question, for in these the adult state may be defined comparatively sharply as the stage of sexual maturity. After that period, though changes in the organism still continue, they are retrogressive changes, and as such might fairly be excluded from any account of development, which clearly implies progression, not retrogression. But, as so often happens in the study of organisms, formulae which apply quite satisfactorily to one group require modifications when others are considered. Does sexual maturity always mark the attainment of the adult state? Is the Axolotl adult when it acquires its reproductive organs? Can a larval Ctenophore, which acquires functional reproductive glands and still possesses the power of passing into the form ordinarily described as adult in that group, be considered to have reached the end of its development? Or—to take the case of those animals, such as Amphioxus, Balanoglossus, and many segmented worms in which important developmental processes occur, e.g. formation of new gill slits, of gonadial sacs, or even of whole segments of the body, long after the power of reproduction has been acquired—how is the attainment of the adult state to be defined, for it is clear that in them the attainment of sexual maturity does not correspond with the end of growth and development? If, then, embryology is to be regarded as including not only the study of embryos, but also that of larvae, i.e. if it includes the study of the whole developmental history of the individual—and it is impossible to treat the subject rationally unless it is so regarded—it becomes exceeding difficult to fix any definite limit to the period of life with which embryology concerns itself. The beginning of this period can be fixed, but not the end, unless it be the end of life itself, i.e. death. The science of embryology, then, is the science of individual development, and includes within its purview all those changes of form and structure, whether embryonic, larval or post-larval, which characterize the life of the individual. The beginning of this period is precise and definite—it is the completion of the fertilization of the ovum, in which the life of the individual has its start. The end, on the other hand, is vague and cannot be precisely defined, unless it be death, in which case the period of life with which embryology concerns itself is coincident with the life of the individual. To use the words of Huxley (“Cell Theory,” Collected Works, vol. i. p. 267): “Development, therefore, and life are, strictly speaking, one thing, though we are accustomed to limit the former to the progressive half of life merely, and to speak of the retrogressive half as decay, considering an imaginary resting-point between the two as the adult or perfect state.”

There are two kinds of reproduction, the sexual and the asexual. The sexual method has for its results an increase of the number of kinds of individual or organism, whereas the asexual affords an increase in the number of individuals of the same kind. If the asexual method Reproduction. of reproduction alone existed, there would, so far as our knowledge at present extends, be no increase in the number of kinds of organism: no new individuality could arise. The first establishment of a new kind of individual by the sexual process is effected in a very similar manner in all Metazoa. The parent produces by a process of unequal fission, which takes place at a part of the body called the reproductive gland, a small living organism called the reproductive cell. There are always two kinds of reproductive cells, and these are generally produced by different animals called the male and female respectively (when they are produced by the same animal it is said to be hermaphrodite). The reproductive cell produced by the male is called the spermatozoon, and that produced by the female, the ovum. These two organisms agree in being small uninucleated masses of protoplasm, but differ considerably in form. They are without the organs of nutrition, &c., which characterize their parents, but the ovum nearly always possesses, stored up within its protoplasm, a greater or less quantity of vitelline matter or food-yolk, while the spermatozoon possesses in almost all cases the power of locomotion. The object with which these two minute and simple organisms are produced is to fuse with one another and give rise to one resultant uninucleated (for the nuclei fuse) organism or cell, which is called the zygote. This process of fusion between the two kinds of reproductive cells, which are termed gametes, is called conjugation: it is the process which is sometimes spoken of as the fertilization of the ovum, and its result is the establishment of a new individual. This new individual at first is simply a uninucleated mass of living matter, which always contains a certain amount of food-yolk, and is generally bounded by a delicate cuticular membrane called the vitelline membrane. In form the newly established zygote resembles the female gamete or ovum—so much so, indeed, that it is frequently called the ovum; but it must be clearly understood that although the bulk of its matter has been derived from the ovum, it consists of ovum and spermatozoon, and, as shown by its subsequent behaviour, the spermatozoon has quite as much to do with determining its vital properties as the ovum.

To the unaided eye the main difference between the newly formed zygotes of different species of animals is that of bulk, and this is due to the amount of food-yolk held in suspension in the protoplasm. The ovum of the fowl is 30 mm. in diameter, that of the frog 1·75 mm., while the ova of the rabbit and Amphioxus have a diameter of ·l mm. The food-yolk is deposited in the ovum as a result of the vital activity of its protoplasm, while the ovum is still a part of the ovary of the parent. It is an inert substance which is used as food later on by the developing embryo, and it acts as a dilutant of the living matter of the ovum. It has a profound influence on the subsequent developmental process. The newly formed zygotes of different species of animals have undoubtedly, as staved above, a certain family resemblance to one another; but however great this superficial resemblance may be, the differences must be most profound, and this fact becomes at once obvious when the properties of these remarkable masses of matter are closely investigated.

As in the case of so many other forms of matter, the more important properties of the zygote do not become apparent until it is submitted to the action of external forces. These forces constitute the external conditions of existence, and the properties which are called forth Causes of development. by their action are called the acquired characters of the organism. The investigation of these properties, particularly of those which are called forth in the early stages of the process, constitutes the science of Embryology. With regard to the manifestation of these properties, certain points must be clearly understood at the outset:—(1) If the zygote is withheld from the appropriate external influences, e.g. if a plant-seed be kept in a box free from moisture or at a low temperature, no properties are evolved, and the zygote remains apparently unchanged; (2) the acquisition of the properties which constitutes the growth and development of the organism proceeds in a perfectly definite sequence, which, so far as is known, cannot be altered; (3) just as the features of the growing organism change under the continued action of the external conditions, so the external conditions themselves must change as the organism is progressively evolved. With regard to this last change, it may be said generally that it is usually, if not always, effected by the organism itself, making use of the properties which it has acquired at earlier stages of its growth, and acting in response to the external conditions. There is, to use a phrase of Mr Herbert Spencer, a continuous adjustment between the external and internal relations. For every organism a certain succession of conditions is necessary if the complete and normal evolution of properties is to take place. Within certain limits, these conditions may vary without interfering with the normal evolution of the properties, though such variations are generally responded to by slight but unimportant variation of the properties (variation of acquired characters). But if the variation of the conditions is too great, the evolved properties become abnormal, and are of such a nature as to preclude the normal evolution of the organism; in other words, the action of the conditions upon the organism is injurious, causing abortions and, ultimately, death. For many organisms the conditions of existence are well known for all stages of life, and can be easily imitated, so that they can be reared artificially and kept alive and made to breed in confinement—e.g. the common fowl. But in a large number of cases it is not possible, through ignorance of the proper conditions, or on account of the difficulty of imitating them, to make the organism evolve all its properties. For instance, there are many marine larvae which have never been reared beyond a certain point, and there are some organisms which, even when nearly full-grown—a stage of life at which it is generally most easy to ascertain and imitate the natural conditions—will not live, or at any rate will not breed, in captivity. Of late years some naturalists have largely occupied themselves with experimental observation of the effects on certain organisms of marked and definite changes of the conditions, and the name of Developmental Mechanics (or Physiology of Development) has been applied to this branch of study (see below).

In normal fertilization, as a rule, only one spermatozoon fuses with the ovum. It has been observed in some eggs that a membrane, formed round the ovum immediately after the entrance of the spermatozoon, prevents the entrance of others. If than one spermatozoon enters, a corresponding Gametogeny. number of male pronuclei are formed, and the subsequent development, if it takes place at all, is abnormal and soon ceases. An egg by ill-treatment (influence of chloroform, carbonic acid, &c.) can be made to take more than one spermatozoon. In some animals it appears that several spermatozoa may normally enter the ovum (some Arthropoda, Selachians, Amphibians and Mammals), but of these only one forms a male pronucleus (see below), the rest being absorbed. Gametogeny is the name applied to the formation of the gametes, i.e. of the ova and spermatozoa. The cells of the reproductive glands are the germ cells (oögonia, spermatogonia). They undergo division and give rise to the progametes, which in the case of the female are sometimes called oöcytes, in the case of the male spermatocytes. The oöcytes are more familiarly called the ovarian ova. The nucleus of the oöcyte is called the germinal vesicle. The oöcyte (progamete) gives rise by division to the ovum or true gamete, the nucleus of which is called the female pronucleus. As a general rule the oöcyte divides unequally twice, giving rise to two small cells called polar bodies, and to the ovum. The first formed polar body frequently divides when the oöcyte undergoes its second and final division, so that there are three polar bodies as well as the ovum resulting from the division of the oöcyte or progamete. Sometimes the ovum arises from the oöcyte by one division only, and there is only one polar body (e.g. mouse, Sobotta, Arch. f. mikr. Anat., 1895, p. 15). The polar bodies are oval, but as a rule they are so small as to be incapable of fertilization. They may therefore be regarded as abortive ova. In one case, however (see Francotte, Bull. Acad. Belg. (3), xxxiii., 1897, p. 278), the first formed polar body is nearly as large as the ovum, and is sometimes fertilized and develops. The spermatogonia are the cells of the testis; these produce by division the spermatocytes (progametes), which divide and give rise to the spermatids. In most cases which have been investigated the divisions by which the spermatids arise from the spermatocytes are two in number, so that each spermatocyte gives origin to four spermatids. Each spermatid becomes a functional spermatozoon or male gamete. The gametogeny of the male therefore closely resembles that of the female, differing from it only in the fact that all the four products of the progamete become functional gametes, whereas in the female only one, the ovum, becomes functional, the other three (polar bodies) being abortive. In the spermatogenesis of the bee, however, the spermatocyte only divides once, giving rise to a small polar-body-like structure and one spermatid (Meves, Anat. Anzeiger, 24, 1904, pp. 29-32). The nucleus of the male gamete is not called the male pronucleus, as would be expected, that term being reserved for the second nucleus which appears in the ovum after fertilization. As this is in all probability derived entirely from the nucleus of the spermatozoon, we should be almost justified in calling the nucleus of the spermatozoon the male pronucleus. In most forms in which the formation of the gametes from the progamete has been accurately followed, and in which the progamete of both sexes divides twice in forming the gametes, the division of the nucleus presents certain peculiarities. In the first place, between the first division and the second it does not enter into the resting state, but immediately proceeds to the second division. In the second place, the number of chromosomes which appear in the final divisions of the progametes and assist in constituting the nuclei of the gametes is half the number which go to constitute the new nuclei in the ordinary nuclear divisions of the animal. The number of chromosomes of the nucleus of the gamete is therefore reduced, and the divisions by which the gametes arise from the progametes are called reducing (maiotic) divisions. It is not certain, however, that this phenomenon is of universal occurrence, or has the significance which is ordinarily attributed to it. In the parthenogenetic ova of certain insects, e.g. Rhodites rosae (Henking), Nematus lacteus (Doncaster, Quart. Journal Mic. Science, 49, 1906, pp. 561-589), reduction does not occur, though two polar bodies are formed.

As soon as the spermatozoon has conjugated with the ovum, a second nucleus appears in the ovum. This is undoubtedly derived from the spermatozoon, possibly from its nucleus only, and is called the male pronucleus. It possesses in the adjacent protoplasm a well-marked centrosome. The Fertilization. general rule appears to be that the female pronucleus is without a centrosome, and that no centrosome appears in the female in the divisions by which the gamete arises from the progamete. If this is true, the centrosome of the zygote nucleus must be entirely derived from that of the male pronucleus. This accounts for the fact, which has been often observed, that the female pronucleus is not surrounded by protoplasmic radiations, whereas such radiations are present round the male pronucleus in its approach to the female. In the mouse the subsequent events are as follow:—Both pronuclei assume the resting form, the chromatin being distributed over the nuclear network, and the nuclei come to lie side by side in the centre of the egg. A long loop of chromatin then appears in each nucleus and divides up into twelve pieces, the chromosomes. The centrosome now divides, the membranes of both nuclei disappear, and a spindle is formed. The twenty-four chromosomes arrange themselves at the centre of this spindle and split longitudinally, so that forty-eight chromosomes are formed. Twenty-four of these, twelve male and twelve female, as it is supposed, travel to each pole of the spindle and assist in giving rise to the two nuclei. At the next nuclear division twenty-four chromosomes appear in each nucleus, each of which divides longitudinally; and so in all subsequent divisions. The fusion of the two pronuclei is sometimes effected in a manner slightly different from that described for the mouse. In Echinus, for instance, the two pronuclei fuse, and the spindle and chromosomes are formed from the zygote nucleus, whereas in the mouse the two pronuclei retain their distinctness during the formation of the chromosomes. There appears, however, to be some variation in this respect: cases have been observed in the mouse in which fusion of the pronuclei occurs before the separation of the chromosomes.

Parthenogenesis, or development of the female gamete without fertilization, is known to occur in many groups of the animal kingdom. Attempts have been made to connect this phenomenon with peculiarities in the gametogeny. For instance, it has been said that parthenogenetic ova Parthenogenesis. form only one polar body. But, as we have seen, this is sometimes the case in eggs which are fertilized, and parthenogenetic ova are known which form two polar bodies, e.g. ova of the honey-bee which produce drones (Morph. Jahrb. xv., 1889, p. 85). ova of Rotifera which produce males (Zool. Anzeiger, xx., 1897, p. 455), ova of some saw-flies and gall flies which produce females (L. Doncaster, Quart. Journ. Mic. Sc., 49, 1906, pp. 561-589). Again it has been asserted that in parthenogenetic eggs the polar bodies are not extruded from the ovum; in such cases, though the nucleus divides, those of its products which would in other cases be extruded in polar bodies remain in the protoplasm of the ovum. But this is not a universal rule, for in some cases of parthenogenesis polar bodies are extruded in the usual way (Aphis, some Lepidoptera), and in some fertilized eggs the polar bodies are retained in the ovum.

It is quite probable that parthenogenesis is more common than has been supposed, and it appears that there is some evidence to show that ova, which in normal conditions are incapable of developing without fertilization, may yet develop if subjected to an altered environment. For instance, it has been asserted that the addition of a certain quantity of chloride of magnesium and other substances to sea-water will cause the unfertilized ova of certain marine animals (Arbacia, Chaetopterus) to develop (J. Loeb, American Journal of Physiology, ix., 1901, p. 423); and according to M. Y. Delage (Comptes rendus, 135, 1902. Nos. 15 and 16) such development may occur after the formation of polar bodies, the chromosomes undergoing reduction and the full number being regained in the segmenting stage. These experiments, if authenticated, suggest that ova have the power of development, but are not able to exercise it in their normal surroundings. There is reason to believe that the same assertion may be made of spermatozoa. Phenomena of the nature of parthenogenesis have never been observed in the male gamete, but it has been suggested by A. Giard (Cinquantenaire de la Soc. de Biol., 1900) that the phenomenon of the so-called fertilization of an enucleated ovum which has been described by T. Boveri and Delage in various eggs, and which results in development up to the larval form (merogony), is in reality a case in which the male gamete, unable to undergo development in ordinary circumstances on account of its small size and specialization of structure has obtained a nutritive environment which enables it to display its latent power of development. Moreover, A. M. Giard suggests that in some cases of apparently normal fertilization one of the pronuclei may degenerate, the resultant embryo being the product of one pronucleus only. In this way he explains certain cases of hybridization in which the paternal (rarely the maternal) type is exclusively reproduced. For instance, in the batrachiate Amphibia, Héron Royer succeeded in 1883 in rearing, out of a vast number of attempts, a few hybrids between a female Pelobates fuscus and a male Rana fusca; the product was a Rana fusca. He also crossed a female Bufo vulgaris with a male Bufo calamita; in the few cases which reached maturity the product was obviously a Bufo calamita. Finally, H. E. Ziegler (Arch. f. Ent.-Mech., 1898, p. 249) divided the just-fertilized ovum of a sea-urchin in such a way that each half had one pronucleus; the half with the male pronucleus segmented and formed a blastula, the other degenerated. It is said that in a few species of animals males do not occur, and that parthenogenesis is the sole means of reproduction (a species of Ostracoda among Crustacea; species of Tenthredinidae, Cynipidae and Coccidae among Insecta); this is the thelytoky of K. T. E. von Siebold. The number of species in which males are unknown is constantly decreasing, and it is quite possible that the phenomenon does not exist. Parthenogenesis, however, is undoubtedly of frequent occurrence, and is of four kinds, namely, (1) that in which males alone are produced, e.g. honey-bees (arrhenotoky); (2) that in which females only are produced (thelytoky), as in some saw-flies; (3) that in which both sexes are produced (deuterotoky), as in some saw-flies; (4) that in which there is an alternation of sexual and parthenogenetic generations, as in Aphidae, many Cynipidae, &c. It would appear that “parthenogenesis does not favour the production of one sex more than another, but it is clear that it decidedly favours the production of a brood that is entirely of one sex, but which sex that is differs according to circumstances” (D. Sharp, Cambridge Natural History, “Insects,” pt. i. p. 498). In some Insecta and Crustacea exceptional parthenogenesis occurs: a certain proportion of the eggs laid are capable of undergoing either the whole or a part of development parthenogenetically, e.g. Bombyx mori, &c. (A. Brauer, Arch. f. mikr. Anat., 1893; consult also E. Maupas on parthenogenesis of Rotifera, Comp. rend., 1889–1891, and R. Lauterborn, Biol. Centralblatt, xviii., 1898, p. 173).

The question of the determination of sex may be alluded to here. Is sex determined at the act of conjugation of the two gametes? Is it, in other words, an unalterable property of the zygote, a genetic character? Or does it depend upon the conditions to which the zygote is subjected in Determination
of sex.
its development? In other words, is it an acquired character? It is impossible in the present state of knowledge to answer these questions satisfactorily, but the balance of evidence appears to favour the view that sex is an unalterable, inborn character. Thus those twins which are believed to come from a split zygote are always of the same sex, members of the same litter which have been submitted to exactly similar conditions are of different sexes, and all attempts to determine the sex of offspring in the higher animals by treatment have failed. On the other hand, the male bee is a portion of a female zygote—the queen-bee. The same remark applies to the male Rotifer, in which the zygote always gives rise to a female, from which the male arises parthenogenetically, but in these cases it does not appear that the production of males is in any way affected by external conditions (see R. C. Punnett, Proc. Royal Soc., 78 B, 1906, p. 223). It is said that in human societies the number of males born increases after wars and famines, but this, if true, is probably due to an affection of the gametes and not of the young zygote. For a review of the whole subject see L. Cuénot, Bull. sci. France et Belgique, xxxii., 1899, pp. 462-535.

The first change the zygote undergoes in all animals is what is generally called the segmentation or cleavage of the ovum. This consists essentially of the division of the nucleus into a number of nuclei, around which the protoplasm sooner or later becomes arranged in the manner ordinarily spoken of as cellular. This division of the nucleus is effected by the process called Cleavage. binary fission; that is to say, it first divides into two, then each of these divides simultaneously again into two, giving four nuclei; each of these after a pause again simultaneously divides into two. So the process continues for some time until the ovum becomes possessed of a large number of nuclei, all of which have proceeded from the original nucleus by a series of binary fissions. This division of the nucleus, which constitutes the essential part of the cleavage of the ovum, continues through the whole of life, but it is only in the earliest period that it is distinguished by a distinct name and used to characterize a stage of development. The nuclear division of cleavage is usually at first a rhythmical process; all the nuclei divide simultaneously, and periods of nuclear activity alternate with periods of rest. Nuclear divisions may be said to be of three kinds, according to the accompanying changes in the surrounding protoplasm: (1) accompanied by no visible change, e.g. the multinucleated Protozoon Actinosphaerium; (2) accompanied by a rearrangement of the protoplasm around each nucleus, but not by its division into two separate masses, e.g. the division which results in the formation of a colony of Protozoa; (3) accompanied by the division of the protoplasm into two parts, so that two distinct cells result, e.g. the divisions by which the free wandering leucocytes are produced, the reproduction of uninuclear Protozoa, &c. In the cleavage of the ovum the first two of these methods of division are found, but probably not the third. At one time it was thought that the nuclear divisions of cleavage were always of the third kind, and the result of cleavage was supposed to be a mass of isolated cells, which became reunited in the subsequent development to give rise to the later connexion between the tissues which were known to exist. But in 1885 it was noticed that in the ovum of Peripatus capensis (A. Sedgwick, Quart. Journ. Mic. Science, xxv., 1885, p. 449) the extra-nuclear protoplasm did not divide in the cleavage of the ovum, but merely became rearranged round the increasing nuclei; the continuity of the protoplasm was not broken, but persisted into the later stages of growth, and gave rise to the tissue-connexions which undoubtedly exist in the adult. This discovery was of some importance, because it rendered intelligible the unity of the embryo so far as its developmental processes are concerned, the maintenance of this unity being somewhat surprising on the previous view. On further inquiry and examination it was found that the ova of many other animals presented a cleavage essentially similar to that of Peripatus. Indeed, it was found that the nuclear divisions of cleavage were of the first two kinds just described. In some eggs, e.g. the Alcyonaria, the first nuclear divisions are effected on the first plan, i.e. they take place without at first producing any visible effect upon the protoplasm of the egg. But in the later stages of cleavage the protoplasm becomes arranged around each nucleus and related to it as to a centre. In the majority of eggs, however, the protoplasm, though not undergoing complete cleavage, becomes rearranged round each nucleus as these are formed. The best and clearest instance of this is afforded by many Arthropodan eggs, in which the nucleus of the just-formed zygote takes up a central position, where it undergoes its first division, subsequent divisions taking place entirely within the egg and not in any way affecting its exterior. The result is to give rise to a nucleated network or foam-work of protoplasm, ramifying through the yolk-particles and containing these in its meshes.

In other Arthropodan eggs the cleavage is on the so-called centrolecithal type, in which the dividing nuclei pass to the cortex of the ovum, and the surface of the ovum becomes indented with grooves corresponding to each nucleus. In this kind of cleavage all the so-called segments are continuous with the central undivided yolk-mass. It sometimes happens that in Arthropods the egg breaks up into masses, which cannot be said to have the value of cells, as they are frequently without nuclei. In other eggs, characterized by a considerable amount of yolk, e.g. the ova of Cephalopoda, and of the Vertebrata with much yolk, the first nucleus takes up an eccentric position in a small patch of protoplasm which is comparatively free from yolk-particles. This patch is the germinal disc, and the nuclear divisions are confined to it and to the transitional region, where it merges into the denser yolk which makes up the bulk of the egg. At the close of segmentation the germinal disc consists of a number of nuclei, each surrounded by its own mass of protoplasm, which is, however, not separated from the protoplasm round the neighbouring nuclei, as was formerly supposed, but is continuous at the points of contact. In this manner the germinal disc has beecome converted into the blastoderm, which consists of a small watch-glass-shaped mass of so-called cells resting on, but continuous with, the large yolk-mass. It is characteristic of this kind of ovum that there is always a row of nuclei, called the yolk-nuclei, placed in the denser yolk immediately adjacent to the blastoderm. These nuclei are continually undergoing division, one of the products of division, together with a little of the sparse yolk protoplasm, passing into the blastoderm to reinforce it (so-called formative cells). The other product of the dividing yolk-nuclei remains in the yolk, in readiness for the next division. In this manner nucleated masses of protoplasm are continually being added to the periphery of the blastoderm and assisting in its growth. But it must be borne in mind that all the nucleated masses of which the blastoderm consists are in continuity with each other and with the sparse protoplasmic reticulum of the subjacent yolk.

In the great majority of eggs, then, the nuclear division of cleavage is not accompanied by a complete division of the ovum into separate cells, but only by a rearrangement of the protoplasm, which produces, indeed, the so-called cellular arrangement, and an appearance only of separate cells. But there still remain to be mentioned those small eggs in which the amount of yolk is inconsiderable, and in which division of the nuclei does appear to be accompanied by a complete division of the surrounding protoplasm into separate unconnected cells—ova of many Annelida, Mollusca, Echinoderma, &c., and of Mammalia amongst Vertebrata. In the case of these also (G. F. Andrews, Zool. Bulletin, ii., 1898) it has been shown that the apparently separate spheres are connected by a number of fine anastomosing threads of a hyaline protoplasm, which are not easy to detect and are readily destroyed by the action of reagents. It is therefore probable that the divisions of the nuclei in cleavage are in no case accompanied by complete division of the surrounding protoplasm, and the organism in the cleavage stage is a continuous whole, as it is in all the other stages of its existence.

Of late years a great number of experiments have been made to discover the effects of dividing the embryo during its cleavage, and of destroying certain portions of it. These experiments have been made with the object of testing the view, held by some authorities, that certain segments Division of embryo. are already set apart in cleavage to give rise to certain adult organs, so that if they were destroyed the organs in question could not be developed. The results obtained have not borne out this view. Speaking generally, it may be said that they have been different according to the stage at which the separation was effected and the conditions under which the experiment was carried out. If the experiment be made at a sufficiently early stage, each part, if not too small, will develop into a normal, though small, embryo. In some cases the embryo remained imperfect for a certain time after the experiment, but the loss is eventually made good by regeneration. (For a summary of the work done on this subject see R. S. Bergh, Zool. Centralblatt, vii., 1900, p. 1.)

The end of cleavage is marked by the commencement of the differentiation of the organs. The first differentiation is the formation of the layers. These are three in number, being called respectively the ectoderm, endoderm and mesoderm, or, in embryos in which at their first The layer theory. appearance they lie like sheets one above the other, the epiblast, hypoblast and mesoblast. The layers are sometimes spoken of as the primary organs, and their importance lies in the fact that they are supposed to be generally homologous throughout the series of the Metazoa. This view, which is based partly on their origin and partly on their fate, had great influence on the science of comparative anatomy during the last thirty years of the 19th century, for the homology of the layers being admitted, they afforded a kind of final court of appeal in determining questions of doubtful homologies between adult organs. Great importance was therefore attached to them by embryologists, and both their mode of development and the part which they play in forming the adult organs were examined with the greatest care. It is very unusual for all the layers to be established at the same time. As a general rule the ectoderm and endoderm, which may be called the primary layers, come first, and later the mesoderm is developed from one or other of them. There are two main methods in which the first two are differentiated—invagination and delamination. The former is generally found in small eggs, in which the embryo at the close of cleavage assumes the form of a sphere, having a fluid or gelatinous material in its centre, and bounded externally by a thin layer of protoplasm, in which all the nuclei are contained. Such a sphere is called a blastosphere, and may be regarded as a spherical mass of protoplasm, of which the central portion is so much vacuolated that it seems to consist entirely of fluid. The central part of the blastosphere is called the segmentation cavity or blastocoel. The blastosphere soon gives rise, by the invagination of one part of its wall upon the other, and a consequent obliteration of the segmentation cavity, to a double-walled cup with a wide opening, which, however, soon becomes narrowed to a small pore. This cup-stage is called the gastrula stage; the outer wall of the gastrula is the ectoderm, and its inner the endoderm; while its cavity is the enteron, and the opening to the exterior the blastopore. Origin of the primary layers by delamination occurs universally in eggs with large yolks (Cephalopoda and many Vertebrata), and occasionally in others. In it cleavage gives rise to a solid mass, which divides by delamination into two layers, the ectoderm and endoderm. The main difference between the two methods of development lies in the fact that in the first of them the endoderm at its first origin shows the relations which it possesses in the adult, namely, of forming the epithelial wall of the enteric space, whereas in the second method the endoderm is at first a solid mass, in which the enteric space makes its appearance later by excavation. In the delaminate method the enteric space is at first without a blastopore, and sometimes it never acquires this opening, but a blastopore is frequently formed, and the two-layered gastrula stage is reached, though by a very different route from that taken in the formation of the invaginate gastrula. According to the layer-theory, these two layers are homologous throughout the series of Metazoa; their limits can always be accurately defined, they give rise to the same organs in all cases, and the adult organs (excluding the mesodermal organs) can be traced back to one or other of them with absolute precision. Thus the ectoderm gives rise to the epidermis, to the nervous system, and to the lining of the stomodaeum and proctodaeum, if such parts of the alimentary canal are present. The endoderm, on the other hand, gives rise to the lining of the enteron, and of the glands which open into it.

So far as these two layers are concerned, and excluding the mesoderm, it would appear that the layer-theory does apply in a very remarkable manner to the whole of the Metazoa. But even here, when the actual facts are closely scanned, there are found to be difficulties, which appear to indicate that the theory may not perhaps be such an infallible guide as it seems at first sight. Leaving out of consideration the case of the Mammalia, in which the differentiation of the segmented ovum is not into ectoderm and endoderm, and the case of the sponges, the most important of these difficulties concern the stomodaeum and proctodaeum. The best case to examine is that of Peripatus capensis, in which the blastopore is at first a long slit, and gives rise to both the mouth and the anus of the adult. Here there is always found at the lips of the blastopore, and extending for a short distance inwards as enteric lining, a certain amount of tissue, which by its characters must be regarded as ectoderm. Now, in the closure of the blastopore between the mouth and anus, this tissue, which at the mouth and anus develops into the lining of the stomodaeum and proctodaeum, is left inside, and actually gives rise to the median ventral epithelium of the alimentary canal. Hence the development of Peripatus capensis suggests the conclusion, if we strictly apply the layer-theory, that a considerable portion of the true mesenteron is lined by ectoderm, and is not homologous with the corresponding portion of the mesenteron of other animals—a conclusion which will on all hands be admitted to be absurd. The difficulties in the application of the layer-theory become vastly greater when the Mesoderm. origin and fate of the mesoderm is considered. The mesoderm is, if we may judge from the number of organs which are derived from it, much the most important of the three layers. It generally arises later than the others, and in its very origin presents difficulties to the theory, which are much increased when we consider its history. It is generally, though not always, developed from the endoderm, either as hollow outgrowths containing prolongations of the enteric cavity, which become the coelom, or as solid proliferations. But in some groups the mesoderm is actually laid down in cleavage, and is present at the end of that process. In others it is entirely derived from the ectoderm (Peripatus capensis). In yet others it is partly derived from endoderm and partly from ectoderm (primitive streak of amniotic Vertebrates). Finally, in whatever manner the first rudiments are developed, it frequently receives considerable reinforcements from one of the primary layers. For instance, the structure known as the nerve crest of the vertebrate embryo is not, as was formerly supposed, exclusively concerned with the formation of the spinal nerves and ganglia, but contributes largely to the mesoderm of the axial region of the body. This is particularly clearly seen in the case of the anterior part of the head of Elasmobranch and probably of other vertebrate embryos, where all the mesoderm present is derived from the anterior part of the neural crest (Quart. Journ. Mic. Science, xxxvii. p. 92).

The layer-theory, then, will not bear critical examination. It is clear, both from their origin and history, that the layers or masses of cells called ectoderm, endoderm and mesoderm have not the same value in different animals; indeed, it is misleading to speak of three layers. At the most we can only speak of two, for the mesoderm is formed after the others, has a composite origin, and has no more claim to be considered an embryonic layer than has the rudiment of the central nervous system, which in some animals, indeed, appears as soon as the mesoderm. Arguments as to homology, based on derivation or non-derivation from the same embryonic layer, have therefore in themselves but little value.

It has frequently been asserted that the reproductive cells are marked off at a very early stage of the development (Sagitta, certain Crustacea, Scorpio). Recently it has been asserted that in Ascaris (T. Boveri, Kuppfer’s Festschrift, 1899, p. 383) the reproductive cells are set apart after the first cleavage, and that they can be traced by certain peculiarities of their nuclei into the adult reproductive glands.

It has been already stated that the mesoderm is a composite tissue. This fact is frequently conspicuous at its first establishment. In many Coelomata it is present under two forms from the beginning. One of these is epithelial in character, while the other has the form of a network of protoplasm, Mesenchyme. with nuclei at the nodes. The former is called simply epithelial mesoderm, the latter mesenchyme. Sometimes the epithelial mesoderm is the first formed, and what little mesenchyme there is is developed from it (Amphioxus, Balanoglossus, &c.) Sometimes the mesenchyme is the first to arise, the epithelial mesoderm developing from it (most, if not all, Vertebrates). Finally, it sometimes happens that these two kinds of tissue arise separately from one or other of the primary layers (Echinodermata). As already hinted, in Balanoglossus and Amphioxus the whole of the mesoderm of the body is at first in an epithelial condition, being developed as an outgrowth of the gut-wall. In Peripatus capensis also, and possibly in other Arthropods, it has at first an intermediate form, being derived from a primitive streak and not from the gut-wall, but it rapidly assumes an epithelial structure, from which all the mesodermal tissues are developed. In Annelids the bulk of the mesoderm has at first a modified epithelial form similar to that of Arthropods, but it is formed, not from a primitive streak, but from some peculiar cells produced in cleavage, called pole-cells. In Annelids with trochosphere larvae a certain amount of mesenchyme is formed at an earlier stage and gives rise to the muscular bands of the young larva. In Echinodermata a certain amount of mesenchyme appears before the epithelial mesoderm, which is formed later as gut-diverticula. In these forms the mesenchyme is said to arise as wandering amoeboid cells, which are budded into the blastocoel by the endoderm just before and during its invagination, but the writer has reason to believe that this account of it does not quite describe what happens. It would seem to be more probable that the mesenchyme arises in these forms, as it certainly does in the case of the later-formed mesenchyme of the Vertebrate embryo, as a protoplasmic outflow from its tissue of origin, passing at first along the line of pre-existent protoplasmic strands which traverse the blastocoel, and sending out at the same time processes which branch and anastomose with neighbouring processes (see E. W. MacBride, Proc. Camb. Phil. Soc., 1896, p. 153). In the Vertebrata the whole of the mesoderm has at first the mesenchyme form. Afterwards, when the body-cavity split appears, the bulk of it assumes a kind of modified epithelial condition, which later on yields, by a process of outflow very similar in its character to what has been supposed to occur in the Echinoderm blastula, a considerable mesenchyme of the reticulate character. Mesenchyme is the tissue which in Vertebrate embryology has frequently been called embryonic connective tissue. This name is no doubt due to the fact that it was supposed to consist of isolated stellate cells. It is, however, in no sense of the word connective tissue, because it gives rise to many organs having nothing whatever to do with connective tissue. For instance, in Vertebrata this tissue gives rise to nervous tissue, blood-vessels, renal tubules, smooth muscular fibres, and other structures, as well as to connective and skeletal tissues. The Vertebrata, indeed, are remarkable for the fact that the epithelial tissues of the so-called mesoderm, e.g. the epithelial lining of the body-cavity, and of the renal tubules and urogenital tracts, all pass through the mesenchymatous condition, whereas in Amphioxus, Balanoglossus and presumably Sagitta and the Brachiopoda, all the mesodermal tissues pass through the epithelial condition, most of the mesodermal tissues of the adult retaining this condition permanently. As has been implied in the above account, mesenchyme is usually formed from epithelial mesoderm or from endoderm, or from tissue destined to form endoderm. It is also sometimes formed from ectoderm, as in the Vertebrata at the nerve crest and other places. In some Coelenterata also it appears certain that the ectoderm does furnish tissue of a mesenchymatous nature which passes into the jelly, but this phenomenon takes place comparatively late in life, at any rate after the embryonic period. In this connexion it may be interesting to point out that in many Coelenterates all the tissues of the body retain throughout life the epithelial condition, nothing comparable to mesenchyme ever being formed.

Finally, before leaving this branch of the subject, the fact that the three germinal layers are continuous with one another, and not isolated masses of tissue, may be emphasized. Indeed, an embryo may be defined as a multinucleated protoplasmic mass, in which the protoplasm at any Continuity of
the layers.
surface—whether internal or external—is in the form of a relatively dense layer, while that in the interior is much vacuolated and reduced to a more or less sparse reticulum, the nuclei either being exclusively found in the surface protoplasm, or if the embryo has any bulk and the internal reticulum is at all well developed, at the nodes of the internal reticulum as well.

The origin of some of the more important organs may now be considered. It is a remarkable fact that the mouth and anus develop in the most diverse ways in different groups, but as a rule either one or both of them can be traced into relation with the blastopore, the history of which Mouth and anus. must therefore be examined. In most, if not all, the great groups of the animal kingdom, e.g. in Coelenterata, Annelida, Mollusca, Vertebrata, and in Arthropoda, the blastopore or its representative is placed on the neural surface of the body, and, as will be shown later on, within the limits of the central nerve rudiment. Here it undergoes the most diverse fate, even in members of the same group. For instance, in Peripatus capensis it extends as a slit along the ventral surface, which closes up in the middle, but remains open at the two ends as the permanent mouth and anus. In other Arthropods, though full details have not yet in all cases been worked out, the following general statement may be made:—A blastopore (certain Crustacea) or its representative is formed on the neural surface of the embryo and always becomes closed, the mouth and anus arising as independent perforations later. Here no one would doubt the homology of the mouth and anus throughout the group; yet within the limits of a single genus—Peripatus—they show the most diverse modes of development. In Annelids the blastopore sometimes becomes the mouth (most Chaetopoda); sometimes it becomes the anus (Serpula); sometimes it closes up, giving rise to neither, though in this case it may assume the form of a long slit along the ventral surface before disappearing. In Mollusca its fate presents the same variations as in Annelida. Now in these groups no zoologist would deny the homology of the mouth and anus in the different forms, and yet how very different is their history even in closely allied animals. How are these apparently diverse facts to be reconciled? The only satisfactory explanation which has been offered (Sedgwick, Quart. J. Mic. Science, xxiv., 1884, p. 43) is that the blastopore is homologous in all the groups mentioned, and is the representative of the original single opening into the enteric cavity, such as at present characterizes the Coelenterata. From it the mouth and anus have been derived, as is indicated by its history in Peripatus capensis, and by the variability in its behaviour in closely allied forms; such variability in its subsequent history is due to its specialization as a larval organ, as a result of which it has lost its capacity to give rise to both mouth and anus, and sometimes to either.

That the blastopore does become specialized as a larval organ is obvious in those cases in which it becomes transformed into the single opening with which some larvae are, for a time at least, alone provided, e.g. Pilidium, Echinoderm larvae, &c., and that larval characters have been the principal causes of the form of embryonic characters, strong reason to believe will be adduced later on. In the Vertebrata the behaviour of the blastopore (anus of Rusconi) is also variable in a very remarkable manner. As a rule it is slit-like in form and closes completely, but in most cases one portion of it remains open longer than the rest, as the neurenteric canal. In a few forms (e.g. Newt, Lepidosiren, &c.) the very hindermost portion of the slit-like blastopore remains permanently open as the anus, and from such cases it can be shown that the neurenteric aperture (when present) is derived from a portion of the blastopore just anterior to its hindermost end. The words “hindermost” and “anterior” are used on the assumption that the whole blastopore has retained its dorsal position; as a matter of fact the hindermost part of it—the part which persists or reopens as the anus—loses this position in the course of development and becomes shifted on to the ventral surface. This is clearly seen in Lepidosiren (Kerr, Phil. Trans. cxcii., 1900), in Elasmobranchii, and in Amniota (primitive streak). Moreover, in Lepidosiren, and possibly in some other forms, the anus, i.e. the hind end of the blastopore, is at first contained within the medullary plate and bounded behind by the medullary folds. Later the portions of the medullary plate in the neighbourhood of the anus completely atrophy, and this relation is lost. This extension of the hind end of the blastopore on to the ventral surface, and atrophy of the portion of the medullary plate in relation with it, is a highly important phenomenon, and one to which attention will be again called when the relation of the mouth to the blastopore is being considered. The remarkable fact about the Vertebrata, a feature which that group shares in common with all other Chordata (Amphioxus, Tunicata, Enteropneusta) and with the Echinodermata, is that the mouth has never been traced into relation with the blastopore. For this reason, among others, it has been held by some zoologists that the mouth of the Vertebrata is not homologous with the mouth of such groups as the Annelida, Arthropoda and Mollusca. But, as has been explained above, in face of the extraordinary variability in the history of the mouth and anus in these groups, this view cannot be regarded as in any way established. On the contrary, there are distinct reasons for thinking that the Vertebrate mouth is a derivate of the blastopore. In the first place, in Elasmobranchii (Sedgwick, Quart. Journ. Mic. Sci. xxxiii., 1892, p. 559), and in a less conspicuous form in other vertebrate groups, the mouth has at first a slit-like form, extending from the anterior end of the central nerve-tube backwards along the ventral surface of the anterior part of the embryo. This slit-like rudiment, recalling as it does the form which the blastopore assumes in so many groups and in many Vertebrata, does suggest the view that possibly the mouth of the Vertebrata may in reality be derived from a portion of an originally long slit-like neural blastopore, which has become extended anteriorly on to the ventral surface and has lost its original relation to the nerve rudiment, as has undoubtedly happened with the posterior part, which persists as the anus.

Of the other organs which develop from the two primary layers it is only possible to notice here the central nervous system. This in almost all animals develops from the ectoderm. In Cephalopods among Mollusca—the development of which is remarkable from the almost Central nervous system. complete absence of features which are supposed to have an ancestral significance—and in one or two other forms, it has been said to develop from the mesoderm; but apart from these exceptional and perhaps doubtful cases, the central nervous system of all embryos arises as thickenings of the ectoderm, and in the groups above mentioned, namely, Annelida, Mollusca, Arthropoda and Vertebrata, and probably others, from the ectoderm of the blastoporal surface of the body. This surface generally becomes the ventral surface, but in Vertebrata it becomes the dorsal. These thickened tracts of ectoderm in Peripatus and a few other forms can be clearly seen to surround the blastopore. This relation is retained in the adult in Peripatus, some Mollusca and some Nemertines, in which the main lateral nerve cords are united behind the anus as well as in front of the mouth; in other forms it cannot always be demonstrated, but it can, as in the case of the Vertebrata just referred to, always be inferred; only, in the Invertebrate groups the part of the nerve rudiment which has to be inferred is the posterior part behind the blastopore, whereas in Vertebrata it is the anterior part, namely, that in front of the blastopore, assuming that the mouth is a blastoporal derivate.

In the Echinodermata, Enteropneusta and one or two other groups, it is not possible, in the present state of knowledge, to bring the mouth into relation with the blastopore, nor can the blastopore be shown to be a perforation of the neural surface. For the Echinoderms, at any rate, this fact loses some of the importance which might at first sight be attributed to it when the remarkable organization of the adult and the sharp contrast which exists between it and the larva is remembered. In some Annelids the central nervous system remains throughout life as part of the outer epidermis, but as a general rule it becomes separated from the epidermis and embedded in the mesodermal tissues. The mode in which this separation is effected varies according to the form and structure of the central nervous system. In the Vertebrata, in which this organ has the form of a tube extending along the dorsal surface of the body, it arises as a groove of the medullary plate, which becomes constricted into a canal. The wall of this canal consists of ectoderm, which at an earlier stage formed part of the outer surface of the body, but which after invagination thickens, to give rise to the epithelial lining of the canal and to the nervous tissue which forms the bulk of the canal wall. The fact that the blastopore remains open at the hind end of the medullary plate explains to a certain extent the peculiar relation which always exists in the embryo between the hind end of the neural and alimentary canals. This communication between the hind end of the neural tube and the gut is one of the most remarkable and constant features of the Vertebrate embryo. As has been pointed out, it is not altogether unintelligible when we remember the relation of the blastopore to the medullary plate of the earlier stage, but to give a complete explanation of it is, and probably always will be, impossible. It is no doubt the impress of some remarkable larval condition of the blastopore of a stage of evolution now long past.

In Ceratodus the open part of the blastopore is enclosed by the medullary folds, as in Lepidosiren, and probably persists as the anus, the portion of the folds around the anus undergoing atrophy (Semon, Zool. Forschungsreisen in Australien, 1893, Bd. i. p. 39). In Urodeles the blastopore persists as anus, so far as is known, but the relation to the medullary folds has not been noticed. The same may be said of Petromyzon (A. E. Shipley, Quart. Journ. Mic. Sci. xxviii., 1887).

The nerve tube of the Vertebrata at a certain early stage of the embryo becomes bent ventralwards in its anterior portion, in such a manner that the anterior end, which is represented in the adult by the infundibulum, comes to project backwards beneath the mid-brain. This bend, which Cranial flexure. is called the cranial flexure, takes place through the mid-brain, so that the hind-brain is unaffected by it. The cranial flexure is not, however, confined to the brain: the anterior end of the notochord, which at first extends almost to the front end of the nerve tube (this extension, which is quite obvious in the young embryo of Elasmobranchs, becomes masked in the later stages by the extraordinary modifications which the parts undergo), is also affected by it. Moreover, it affects even other parts, as may be seen by the oblique, almost antero-posterior, direction of the anterior gill slits as compared with the transverse direction of those behind. No satisfactory explanation has ever been offered of the cranial flexure. It is found in all Vertebrates, and is effected at an early stage of the development. In the later stages and in the adult it ceases to be noticeable, on account of an alteration of the relative sizes of parts of the brain. This is due almost entirely to the enormous growth of the cerebral vesicle, which is an outgrowth of the dorsal wall of the fore-brain just short of its anterior end. The anterior end of the fore-brain remains relatively small throughout life as the infundibulum, and the junction of this part of the fore-brain with the part which is so largely developed, as the rudiment of the cerebrum, is marked by the attachment of the optic chiasma. The optic nerve, indeed, is morphologically the first cranial nerve, the olfactory being the second; both are attached to what is morphologically the dorsal side of the nerve tube. The morphological anterior end of the central nerve tube is the point of the infundibulum which is in contact with the pituitary body. While on the subject of the cranial flexure, it may be pointed out that there is a similar downward curve of the hind end of the nervous axis, which leads into the hind end of the enteron. If it be supposed that originally there was a communication between the infundibulum and pituitary body, then the ventral flexure found at both ends of the nerve axis would originally have had the same result, namely, of placing the neural and alimentary canals in communication. Moreover, the mouth would have had much the same relation to this imaginary anterior neurenteric canal that the anus has to the actual posterior one.

In Amphioxus and the Tunicata the early development of the central nervous system is very much like that of the Vertebrata, but the later stages are simpler, being without the cranial flexure. The Tunicata are remarkable for the fact that the nervous system, though at first hollow, becomes quite solid in the adult. In Balanoglossus the central nervous system is in part tubular, the canal being open at each end. It arises, however, by delamination from the ectoderm, the tube being a secondary acquisition. This is probably due to a shortening of development, for the same feature is found in some Vertebrata (Teleostei, Lepidosteus, &c.), where the central canal is secondarily hollowed out in the solid keel-like mass which is separated from the ectoderm. Parts of the central nervous system arise by invagination in other groups; for instance, the cerebral ganglia of Dentalium are formed from the walls of two invaginations of ectoderm, which eventually disappear at the anterior end of the body (A. Kowalevsky, Ann. Mus. Hist. Nat. Marseilles, “Zoology,” vol. i.). In Peripatus the cerebral ganglia arise in a similar way, but in this case the cavities of the invagination become separated from the skin and persist as two hollow appendages on the lower side of the cerebral ganglia. In other Arthropods the cerebral ganglia arise in a similar way, but the invaginations disappear in the adult. In Nemertines the cerebral ganglia contain a cavity which communicates with the exterior by a narrow canal. Finally, in certain Echinodermata the ventral part of the central nervous system arises by the invagination of a linear streak of ectoderm, the cavity of the invagination persisting as the epineural canal.

Although the central nervous system is almost always developed from the ectoderm of the embryo, the same cannot be said of the peripheral nerve trunks. These structures arise from the mesoblastic reticulum already described (Sedgwick, Quart. Journ. Mic. Sci. xxxvii. 92). Inasmuch Peripheral nervous system. as this reticulum is perfectly continuous with the precisely similar though denser tissue in the ectoderm and endoderm, it may well be that a portion of the nerve trunks should be described as being ectodermal and endodermal in origin, though the bulk of them are undoubtedly formed from that portion of the reticulum commonly described as mesoblastic. But, however that may be, the tissue from which the great nerve trunks are developed is continuous on all sides with a similar tissue which pervades all the organs of the body, and in which the nuclei of these organs are contained.

In the early stages of development this tissue is very sparse and not easily seen. It would appear, indeed, that it is of a very delicate texture and readily destroyed by reagents. It is for this reason that the layers of the Vertebrate embryo are commonly represented as being quite isolated from one another, and that the medullary canal is nearly always represented as being completely isolated at certain stages from the surrounding tissues. In reality the layers are all connected together by this delicate tissue—in a sparse form, it is true—which not only extends between them, but also in a denser and more distinct form pervades them. In the germinal layers themselves, and in the organs developing from them, this tissue is in the young stages almost entirely obscured by the densely packed nuclei which it contains. For instance, in the wall of the medullary canal in the Vertebrate embryo, in the splanchnic and somatic layers of mesoderm of the same embryo, and in the developing nerve cords of the Peripatus embryo, the nuclei are at first so densely crowded together that it is almost impossible to see the protoplasmic framework in which they rest, but as development proceeds this extra-nuclear tissue becomes more largely developed, and the nuclei are forced apart, so that it becomes visible and receives various names according to its position. In the wall of the medullary canal of the Vertebrate embryo, on the outside of which it becomes especially conspicuous in certain places, and on the dorsal side of the developing nerve cords of the Peripatus embryo, it constitutes the white matter of the developing nerve cord; in the mesoblastic tissue outside, where it at the same time becomes more conspicuous (Sedgwick, “Monograph of the Development of Peripatus capensis,” Studies from the Morph. Lab. of the University of Cambridge, iv., 1889, p. 131), it forms the looser network of the mesoblastic reticulum; and connecting the two, in place of the few and delicate strands of this tissue of the former stage, there are at certain places well-marked cords of a relatively dense texture, with the meshes of the reticulum elongated in the direction of the cord. This latter structure is an incipient nerve trunk. It can be traced outwards into the mesoblastic reticulum, from the strands of which it is indeed developed, and with which it is continuous not only at its free end, but also along its whole course. In this way the nerve trunks are developed—by a gathering up, so to speak, of the fibres of the reticulum into bundles. These bundles are generally marked by the possession of nuclei, especially in their cortical parts, which become no doubt the nuclei of the nerve sheath, and, in the neighbourhood of the ganglia, of nerve cells. From this account of the early development of the nerves, it is apparent that they are in their origin continuous with all the other tissues of the body, with that of the central nervous system and with that which becomes transformed into muscular tissue and connective and epithelial tissues. All these tissues are developed from the general reticulum, which in the young embryo can be seen to pervade the whole body, not being confined to the mesoderm, but extending between the nuclei of the ectoderm and endoderm, and forming the extra-nuclear, so-called cellular, protoplasm of those layers. Moreover, it must be remarked that in the stages of the embryo with which we are here concerned the so-called cellular constitution of the tissues, which is such a marked feature of the older embryo and adult, has not been arrived at. It is true, indications of it may be seen in some of the earlier-formed epithelia, but of nerve cells, muscular cells, and many kinds of gland cells no distinct signs are yet visible. This remark particularly applies to nerve cells, which do not make their appearance until a much later stage—not, indeed, until some time after the principal nerve trunks and ganglia are indicated as tracts of pale fibrous substance and aggregations of nuclei respectively.

The embryos of Elasmobranchs—particularly of Scyllium—are the best objects in which to study the development of nerves. In many embryos it is difficult to make out what happens, because the various parts of the body remain so close together that the process is obscured, and the loosening of the mesoblastic nuclei is deferred until after the nerves have begun to be differentiated. The process may also be traced in the embryos of Peripatus, where the main features are essentially similar to those above described (op. cit. p. 131). The development of the motor nerves has been worked out in Lepidosiren by J. Graham Kerr (Trans. Roy. Soc. of Edinburgh, 41, 1904. p. 119).

To sum up, the development of nerves is not, as has been recently urged, an outgrowth of cell processes from certain cells, but is a differentiation of a substance which was already in position, and from which all other organs of the body have been and are developed. It frequently happens that the young nerve tracts can be seen sooner near the central organ than elsewhere, but it is doubtful if any importance can be attached to this fact, since it is not constantly observed. For instance, in the case of the third nerve of Scyllium the differentiation appears to take place earliest near the ciliary ganglion, and to proceed from that point to the base of the mid-brain.

There are two main methods in which new organs are developed. In the one, which indicates the possibility of physiological continuity, the organ arises by the direct modification of a portion of a pre-existing organ; the development of the central nervous system of the Vertebrata Coelom. from a groove in the embryonic ectoderm may be taken as an example of this method. In the other method there is no continuity which can be in any way interpreted as physiological; a centre of growth appears in one of the parts of the embryo, and gives rise to a mass of tissue which gradually shapes itself into the required organ. The development of the central nervous system in Teleosteans and in other similar exceptional cases may be mentioned as an example of the second plan. Such a centre of growth is frequently called a blastema, and consists of a mass of closely packed nuclei which have arisen by the growth-activity of the nuclei in the neighbourhood. The coelom, an organ which is found in the so-called coelomate animals, and which in the adult is usually divided up more or less completely into three parts, namely, body-cavity, renal organs, generative glands, presents in different animals both these methods of development. In certain animals it develops by the direct modification of a part of the primitive enteron, while in others it arises by the gradual shaping of a mass of tissue which consists of a compact mass of nuclei derived by nuclear proliferation from one or more of the pre-existing tissues of the body. Inasmuch as the first rudiment of the coelom nearly always makes its appearance at an early stage, when the ectoderm and endoderm are almost the only tissues present, and as it then bulks relatively very large and frequently contains within itself the potential centres of growth of other organs, e.g. mesenchymal organs (see above), it has come to be regarded by embryologists as being the forerunner of all the so-called mesodermal organs of the body, and has been dignified with the somewhat mysterious rank which attaches to the conception of a germinal layer. Its prominence and importance at an early stage led embryologists, as has already been explained, to overlook the fact that although some of the centres of growth for the formation of other non-coelomic mesodermal organs and tissues may be contained within it, all are not so contained, and that there are centres of mesodermal growth still left in the ectoderm and endoderm after its establishment. If these considerations, and others like them, are correct, it would seem to follow that the conception implied by the word mesoderm has no objective existence, that the tissue of the embryo called mesoderm, though sometimes mainly the rudiment of the coelom, is often much more than this, and contains within itself the rudiment of many, sometimes of all, of the organs appertaining to the mesenchyme. In thus containing within itself the potential centres of growth of other organs and tissues which are commonly ranked as mesodermal, it is not different from the rudiments of the two other organs already formed, namely, the ectoderm and endoderm; for these contain within themselves centres of growth for the production of so-called mesodermal tissues, as witness the nerve-crest of Vertebrata, the growing-point of the pronephric duct, and the formation of blood-vessels from the hypoblast described for some members of the same group.

In Echinodermata, Amphioxus, Enteropneusta, and a few other groups, the coelom develops from a portion or portions of the primitive enteron, which eventually becomes separated from the rest and forms a variable number of closed sacs lying between the gut and the ectoderm. The number of these sacs varies in different animals, but the evidence at present available seems to show that the maximum number is five—an unpaired one in front and two pairs behind—and, further, that if a less number of sacs is actually separated from the enteron, the rule is for these sacs so to divide up that they give rise to five sacs arranged in the manner indicated. The Enteropneusta present us with the clearest case of the separation of five sacs from the primitive enteron (W. Bateson, Quart. Journ. Mic. Sci. xxiv., 1884). In Amphioxus, according to the important researches of E. W. MacBride (Quart. Journ. Mic. Sci. xl. 589), it appears that a similar process occurs, though it is complicated by the fact that the sacs of the posterior pair become divided up at an early stage into many pairs. In Phoronis there are indications of the same phenomenon (A. T. Masterman, Quart. Journ. Mic. Sci. xliii. 375). In the Chaetognatha a single sac only is separated from the enteron, but soon becomes divided up. In the Brachiopoda one pair of sacs is separated from the enteron, but our knowledge of their later history is not sufficient to enable us to say whether they divide up into the typically arranged five sacs. In Echinodermata the number of sacs separated from the enteron varies from one to three; but though the history of these shows considerable differences, there are reasons to believe that the typical final arrangement is one unpaired and two paired sacs. But however many sacs may arise from the primitive enteron, and however these sacs may ultimately divide up and arrange themselves, the important point of development common to all these animals, about which there can be no dispute, is that the coelom is a direct differentiation of a portion of the enteron.

In the majority of the Coelomata the coelomic rudiment does not arise by the simple differentiation of a pre-existing organ, and there is considerable variation in its method of formation. Speaking generally, it may be said to arise by the differentiation of a blastema (see above), which develops at an early stage as a nuclear proliferation from one or more growth-centres in one or both of the primary layers. It appears in this tissue as a sac or as a series of sacs, which become transformed into the body-cavity (except in the Arthropoda), into the renal organs (with the possible exception, again, of some Arthropoda), and into the reproductive glands. In metamerically segmented animals the appearance of the cavities of these sacs is synchronous with, and indeed determines, the appearance of metameric segmentation. In all segmented animals in which the mesoderm (coelomic rudiment) appears as a continuous sheet or band of tissue on each side of the body, the coelomic cavity makes its first appearance not as a continuous space on each side, which later becomes divided up into the structures called mesoblastic somites, but as a series of paired spaces round which the coelomic tissue arranges itself in an epithelial manner. In the Vertebrata, it is true, the ventral portion of the coelom appears at first as a continuous space, at any rate behind the region of the two anterior pairs of somites, but in the dorsal portion the coelomic cavity is developed in the usual way, the coelomic tissue becoming transformed into the muscle plates and rudimentary renal tubules of the later stages. With regard to this ventral portion of the coelom in Vertebrata, it is to be noticed that the cavity in it never becomes divided up, but always remains continuous, forming the perivisceral portion of the coelom. The probable explanation of this peculiarity in the development of the Vertebrate coelom, as compared with that of Amphioxus and other segmented animals, is that the segmented stage of the ventral portion of the coelom is omitted. This explanation derives some support from the fact that even in animals in which the coelom is at its first appearance wholly segmented, it frequently happens that in the adult the perivisceral portion of it is unsegmented, i.e. it loses during development the segmentation which it at first possesses. This happens in many Annelida and in Amphioxus. The lesson, then, which the early history of the coelom in segmented animals teaches is, that however the coelomic cavity first makes its appearance, whether by evaginations from the primitive enteron, or by the hollowing out of a solid blastema-like tissue which has developed from one or both of the primary layers, it is in its first origin segmented, and forms the basis on which the segments of the adult are moulded. In Arthropoda the origin of the coelom is similar to that of Annelids, but its history is not completely known in any group, with the exception of Peripatus. In this genus it develops no perivisceral portion, as in other groups, but gives rise solely to the nephridia and to the reproductive organs. It is probable, though not certainly proved, that the history of the coelom in other Arthropods is essentially similar to that of Peripatus, allowance being made for the fact that the nephridial portion does not attain full development in those forms which are without nephridia in the adult.

With regard to the development of the vascular system, little can be said here, except that it appears to arise from the spaces of the mesoblastic reticulum. When this reticulum is sparse or so delicate as to give way in manipulation, these spaces appear to be represented by a continuous space which in the earliest stages of development is frequently spoken of as the blastocoel or segmentation cavity. They acquire special epithelial walls, and form the main trunks and network of smaller vessels found in animals with a canalicular vascular system, or the large sinus-like spaces characteristic of animals with a haemocoelic body-cavity.

The existence of a phase at the beginning of life during which a young animal acquires its equipment by a process of growth of the germ is of course intelligible enough; such a phase is seen in the formation of buds, and in the sexual reproduction of both animals and plants. The Transient embryonic organs. remarkable point is that while in most cases this embryonic growth is a direct and simple process—e.g. animal and plant buds, embryonic development of plant seeds—in many cases of sexual reproduction of animals it is not direct, and the embryonic phase shows stages of structure which seem to possess a meaning other than that of being merely phases of growth. The fact that these stages of structure through which the embryo passes sometimes present for a short time features which are permanent in other members of the same group, adds very largely to the interest of the phenomenon and necessitates its careful examination. This may be divided into two heads: (1) in relation to embryos, (2) in relation to larvae. So far as embryos are concerned, we shall limit ourselves mainly to a consideration of the Vertebrata, because in them are found most instances of that remarkable phenomenon, the temporary assumption by certain organs of the embryo of stages of structure which are permanent in other members of the same group. As is well known, the embryos of the higher Vertebrata possess in the structure of the pharynx and of the heart and vascular system certain features—namely, paired pharyngeal apertures, a simple tubular heart, and a single ventral aorta giving off right and left a number of branches which pass between the pharyngeal apertures—which permanently characterize those organs in fishes. The skeleton, largely bony in the adult, passes through a stage in which it is entirely without bone, and consists mainly of cartilage—the form which it permanently possesses in certain fishes. Further, the Vertebrate embryo possesses for a time a notochord, a segmented muscular system, a continuity between the pericardium and the posterior part of the perivisceral cavity—all features which characterize certain groups of Pisces in the adult state. Instances of this kind might be multiplied, for the work of anatomists and embryologists has of late years been largely devoted to adding to them. Examples of embryonic characters which are not found in the adults of other Vertebrates are the following:—At a certain stage of development the central nervous system has the form of a groove in the skin, there is a communication at the hind end of the body between the neural and alimentary canals, the mouth aperture has at first the form of an elongated slit, the growing end of the Wolffian duct is in some groups continuous with the ectoderm, and the retina is at one stage a portion of the wall of the medullary canal. In the embryos of the lower Vertebrates many other instances of the same interesting character might be mentioned; for instance, the presence of a coelomic sac close to the eye, of another in the jaw, and of a third near the ear (Elasmobranchs), the opening of the Müllerian duct into the front end of the Wolffian duct, and the presence of an aperture of communication between the muscle-plate coelom and the nephridial coelom.

The interest attaching to these remarkable facts is much increased by the explanation which has been given of them. That explanation, which is a deduction from the theory of evolution, is to the effect that the peculiar embryonic structures and relations just mentioned are due to the retention by the embryo of features which, once possessed by the adult ancestor, have been lost in the course of evolution. This explanation, which at once suggests itself when we are dealing with structures Recapitulation theory. actually present in adult members of other groups, does not so obviously apply to those features which are found in no adult animal whatsoever. Nevertheless it has been extended to them, because they are of a nature which it is not impossible to suppose might have existed in a working animal. Now this explanation, which, it will be observed, can only be entertained on the assumption that the evolution theory is true, has been still further extended by embryologists in a remarkable and frequently unjustifiable manner, and has been applied to all embryonic processes, finally leading to the so-called recapitulation theory, which asserts that embryonic history is a shortened recapitulation of ancestral history, or, to use the language of modern zoology, that the ontogeny or development of the individual contains an abbreviated record of the phylogeny or development of the race. A theory so important and far-reaching as this requires very careful examination. When we come to look for the facts upon which it is based, we find that they are non-existent, for the ancestors of all living animals are dead, and we have no means of knowing what they were like. It is true there are fossil remains of animals which have lived, but these are so imperfect as to be practically useless for the present requirements. Moreover, if they were perfectly preserved, there would be no evidence to show that they were ancestors of the animals now living. They might have been animals which have become extinct and left no descendants. Thus the explanation ordinarily given of the embryonic structures referred to is purely a deduction from the evolution theory. Indeed, it is even less than this, for all that can be said is something of this kind: if the evolution theory is true, then it in conceivable that the reason why the embryo of a bird passes through a stage in which its pharynx presents some resemblance to that of a fish is that a remote ancestor of the bird possessed a pharynx with lateral apertures such as are at present found in fishes.

But the explanation is sometimes pushed even further, and it is said that these pharyngeal apertures of the ancestral bird had the same respiratory function as the corresponding structures in modern fishes. That this is going too far a little reflection will show. For if it be admitted that all so-called vestigial structures had once the same function as the homologous structures when fully developed in other animals, it becomes necessary to admit that male mammals must once have had fully developed mammary glands and suckled the young, that female mammals formerly were provided with a functional penis, and that in species in which the females have a trace of the secondary sexual characters of the male the latter were once common to both sexes. The second and more extended form of the explanation plainly introduces a considerable amount of contentious matter, and it will be advisable, in the first instance, at any rate, to confine ourselves to a critical examination of the less ambitious conception. This explanation obviously implies the view that in the course of evolution the tendency has been for structures to persist in the embryo after they have been lost in the adult. Is there any justification for this view? It is clearly impossible to get any direct evidence, because, as explained above, we have no knowledge of the ancestors of living animals; but if we assume the evolution theory to be true, there is a certain amount of indirect evidence which is distinctly opposed to the view. As is well known, living birds are without teeth, but it is generally assumed that their edentulous condition has been comparatively recently acquired, and that they are descended from animals which, at a time not very remote from the present, possessed teeth. Considering the resemblance of birds to other terrestrial vertebrates, and the fact that extinct birds, not greatly differing from birds now living, are known to have had teeth, it must be allowed that there is some warrant for the assumption. Yet in no single case has it been certainly shown that any trace of teeth has been developed in the embryo. The same remark applies to a large number of similar cases; for instance, the reduced digits of the bird’s hand and foot and the limbs of snakes. Moreover, organs which are supposed to have become recently reduced and functionless in the adult are also reduced in the embryo; for instance, digits 3 and 4 of the horse’s foot, the hind limbs of whales (G. A. Guldberg and F. Nansen, “On the Development and Structure of Whales,” Bergen Museum, 1894), the spiracle of Elasmobranchii. In fact, considerations of this kind distinctly point to the view that any tendency to the reduction or enlargement of an organ in the adult is shared approximately to the same extent by the embryo. But there are undoubtedly some, though not many, cases in which organs which were presumably present in an ancestral adult have persisted in the embryo of the modern form. As an instance may be mentioned the presence in whale-bone whales of imperfectly formed teeth, which are absorbed comparatively early in foetal life (Julin, Arch. biologie, i., 1880, p. 75).

It therefore becomes necessary to inquire why in some cases an organ is retained by the embryo after its loss by the adult, whereas in other cases it dwindles and presumably disappears simultaneously in the embryo and the adult. The whole question is examined and discussed by the present writer in the Quarterly Journal of Microscopical Science, xxxvi., 1894, p. 35, and the conclusions there reached are as follows:—A disappearing adult organ is not retained in a relatively greater development by an organism in the earlier stages of its individual growth unless it is of functional importance to the young form. In cases in which the whole development is embryonic this rarely happens, because the conditions of embryonic life are so different from free life that functional embryonic organs are usually organs sui generis, e.g. the placenta, amnion, &c., which cannot be traced to a modification of organs previously present in the adult. It does, however, appear to have happened sometimes, and as an instance of it may be mentioned the ductus arteriosus of the Sauropsidan and Mammalian embryo. On the other hand, when there is a considerable period of larval life, it does appear that there is a strong case for thinking that organs which have been lost by the adult may be retained and made use of by the larva. The best-known example that can be given of this is the tadpole of the frog. Here we find organs, viz. gills and gill-slits, which are universally regarded as having been attributes of all terrestrial Vertebrata in an earlier and aquatic condition, and we also notice that their retention is due to their being useful on account of the supposed ancient conditions of life having been retained. Many other instances, more or less plausible, of a like retention of ancestral features by larvae might be mentioned, and it must be conceded that there are strong reasons for supposing that larvae often retain traces, more or less complete, of ancestral stages of structure. But this admission does not carry with it any obligation to accept the widely prevalent view that larval history can in any way be regarded as a recapitulation of ancestral history. Far from it, for larvae in retaining some ancestral features are in no way different from adults; they only differ from adults in the features which they have retained. Both larvae and adults retain ancestral features, and both have been modified by an adaptation to their respective conditions of life which has ever been becoming more perfect.

The conclusion, then, has been reached, that whereas larvae frequently retain traces of ancestral stages of adult structure, embryos will rarely do so; and we are confronted again with the question, How are we to account for the presence in the embryo of numerous functionless organs which cannot be explained otherwise than as having been inherited from a previous condition in which they were functional? The answer is that the only organs of this kind which have been retained are organs which have been retained by the larvae of the ancestors after they have been lost by the adult, and have become in this way impressed upon the development. As an illustration taken from current natural history of the manner in which larval characters are in actual process of becoming embryonic may be mentioned the case of the viviparous salamander (Salamander atra), in which the gills, &c., are all developed but never used, the animal being born without them. In other and closely allied species of salamander there is a considerable period of larval life in which the gills and gill-slits are functional, but in this species the larval stage, for the existence of which there was a distinct reason, viz. the entirely aquatic habits of life in the young state, has become at one stroke embryonic by its simple absorption into the embryonic period. The view, then, that embryonic development is essentially a recapitulation of ancestral history must be given up; it contains only a few references to ancestral history, namely, those which have been preserved probably in a much modified form by previous larvae.

We must now pass to the consideration of another supposed law of embryology—the so-called law of v. Baer. This generalization is usually stated as follows:—Embryos of different species of the same group are more alike than adults, and the resemblances are greater the younger Law of v. Baer. the embryo examined. Great importance has been attached to this generalization by embryologists and naturalists, and it is very widely accepted. Nevertheless, it is open to serious criticism. If it were true, we should expect to find that embryos of closely similar species would be indistinguishable, but this is notoriously not the case. On the contrary, they often differ more than do the adults, in support of which statement the embryos of the different species of Peripatus may be referred to. The generalization undoubtedly had its origin in the fact that there is what may be called a family resemblance between embryos, but this resemblance, which is by no means exact, is purely superficial, and does not extend to anatomical detail. On the contrary, it may be fairly argued that in some cases embryos of widely dissimilar members of the same group present anatomical differences of a higher morphological value than do the adults (see Sedgwick, loc. cit.), and, as stated above the embryos of closely allied animals are distinguishable at all stages of development, though the distinguishing features are not the same as those which distinguish the adults. To say that the development of the organism and of its component parts is a progress from the simple to the complex is to state a truism, but to state that it is also a progress from the general to the special is to go altogether beyond the facts. The bipinnaria larva of an echinoderm, the trochosphere larva of an annelid, the blastodermic vesicle of a mammal are all as highly specialized as their respective adults, but the specialization is for a different purpose, and of a different kind to that which characterizes the adult.

In its scientific and systematic form embryology may be considered as having only taken birth within the last century, although the germ from which it sprung was already formed nearly half a century earlier. The ancients, it is true, as we see by the writings of Aristotle and History of embryology. Galen, pursued the subject with interest, and the indefatigable Greek naturalist and philosopher had even made continued series of observations on the progressive stages of development in the incubated egg, and on the reproduction of various animals; but although, after the revival of learning, various anatomists and physiologists from time to time made contributions to the knowledge of the foetal structure in its larger organs, yet from the minuteness of the observations required for embryological research, it was not till the microscope came into use for the investigation of organic structure that any intimate knowledge was attained of the nature of organogenesis. It is not to be wondered at, therefore, that during a long period, in this as in other branches of physical inquiry, vague speculations took the place of direct observation and more solid information. This is apparent in most of the works treating of generation during the 16th and part of the 17th centuries.[2]

Harvey was the first to give, in the middle of the latter century, a new life and direction to investigation of this subject, by his discovery of the connexion between the cicatricula of the yolk and the rudiments of the chick, and by his faithful description of the successive stages of development as observed in the incubated egg, as well as of the progress of gestation in some Mammalia. He had also the merit of fixing the attention of physiologists upon general laws of development as deduced from actual observation of the phenomena, by the enunciation of two important propositions, viz.—(1) that all animals are produced out of ova, and (2) that the organs of the embryo arise by new formation, or epigenesis, and not by mere enlargement out of a pre-existing invisible condition (Exercitationes de generatione animalium, Amstelodami, 1651). Harvey’s observations, however, were aided only by the use of magnifying glasses (perspecillae), probably of no great power, and he saw nothing of the earliest appearances of the embryo in the first thirty-six hours, and believed the blood and the heart to be the parts first formed.

The influence of the work of Harvey, and of the successful application of the microscope to embryological investigation, was soon afterwards apparent in the admirable researches of Malpighi of Bologna, as evinced by his communications to the Royal Society of London in 1672, “De ovo incubato,” and “De formatione pulli,” and more especially in his delineations of some of the earlier phenomena of development, in which, as in many other parts of minute anatomy, he partially or wholly anticipated discoveries, the full development of which has only been accomplished in the present century. Malpighi traced the origin of the embryo almost to its very commencement in the formation of the cerebro-spinal groove within the cicatricula, which he removed from the opaque mass of the yolk; and he only erred in supposing the embryonal rudiments to have pre-existed as such in the egg, in consequence, apparently, of his having employed for observation, in very warm weather, eggs which, though he believed them to be unincubated, had in reality undergone some of the earlier developmental changes.

The works of Walter Needham (1667), Regnier de Graaf (1673), Swammerdam (1685), Vallisneri (1689)—following upon those of Harvey—all contain important contributions to the knowledge of our subject, as tending to show the similarity in the mode of production from ova in a variety of animals with that previously best known in birds. The observations more especially of de Graaf, Nicolas Steno and J. van Horne gave much greater precision to the knowledge of the connexion between the origin of the ovum of quadrupeds and the vesicles of the ovary now termed Graafian, which de Graaf showed always burst and discharged their contents on the occurrence of pregnancy.

These observations bring us to the period of Boerhaave and Albinus in the earlier part of the 18th century, and in the succeeding years to that of Haller, whose vast erudition and varied and accurate original observations threw light upon the entire process of reproduction in animals, and brought its history into a more systematic and intelligible form. A considerable part of the seventh and the whole of the eighth volumes of Haller’s great work, the Elementa physiologiae, published at successive times from 1757 to 1766, are occupied with the general view of the function of generation, while his special contributions to embryology are contained in his Deux mémoires sur la formation du cœur dans le poulet and Deux mémoires sur la formation des os, both published at Lausanne in 1758, and republished in an extended and altered form, together with his “Observations on the early condition of the Embryo in Quadrupeds,” made along with Kühlemann, in the Opera minora (1762–1768). Though originally educated as a believer in the doctrine of “preformation” by his teacher Boerhaave, Haller was soon led to abandon that view in favour of “epigenesis” or new formation, as may be seen in various parts of his works published before the middle of the century; see especially a long note explanatory of the grounds of his change of opinion in his edition of Boerhaave’s Praelectiones academicae, vol. v. part 2, p. 497 (1744), and his Primae lineae physiologiae (1747). But some years later, and after having been engaged in observing the phenomena of development in the incubated egg, he again changed his views, and during the remainder of his life was a keen opponent of the system of epigenesis, and a defender and exponent of the theory of “evolution,” as it was then named—a theory very different from that now bearing the name, and which implied belief in the pre-existence of the organs of the embryo in the germ, according to the theory of encasement (emboîtement) or inclusion supported by Leibnitz and Bonnet. (See the interesting work of Bonnet, Considérations sur les corps organisés, Amsterdam, 1762, for an account of his own views and those of Haller.)

It was reserved for Caspar Frederick Wolff (1733–1794), a German by birth, but naturalized afterwards in Russia, to bring forward observations which, though almost entirely neglected for a long time after their publication, and in some measure discredited under the influence of Haller’s authority, were sixty years later acknowledged to have established the theory of epigenesis upon the secure basis of ascertained facts, and to have laid the first foundation of the morphological science of embryology. Wolff’s work, entitled Theoria generationis, first published as an inaugural Dissertation at Berlin in 1759, was republished with additions in German at Berlin in 1764, and again in Latin at Halle in 1774. Wolff also wrote a “Memoir on the Development of the Intestine” in Nov. comment. acad. Petropol., 1768 and 1769. But it was not till the latter work was translated into German by J. F. Meckel, and appeared in his Archiv for 1812, that Wolff’s peculiar merits as the founder of modern embryology came to be known or fully appreciated.

The special novelty of Wolff’s discoveries consisted mainly in this, that he showed that the germinal part of the bird’s egg forms a layer of united granules or organized particles (cells of the modern histologist), presenting at first no semblance of the form or structure of the future embryo, but gradually converted by various morphological changes in the formative material, which are all capable of being traced by observation, into the several rudimentary organs and systems of the embryo. The earlier form of the embryo he delineated with accuracy; the actual mode of formation he traced in more than one organ, as for example in the alimentary canal, and he was the discoverer of several new and important embryological facts, as in the instance of the primordial kidneys, which have thus been named the Wolffian bodies. Wolff further showed that the growing parts of plants owe their origin to organized particles or cells, so that he was led to the great generalization that the processes of embryonic formation and of adult growth and nutrition are all of a like nature in both plants and animals. No advance, however, was made upon the basis of Wolff’s discoveries till the year 1817, when the researches of C. H. Pander on the development of the chick gave a fuller and more exact view of the phenomena less clearly indicated by Wolff, and laid down with greater precision a plan of the formation of parts in the embryo of birds, which may be regarded as the foundation of the views of all subsequent embryologists.

But although the minuter investigation of the nature and true theory of the process of embryonic development was thus held in abeyance for more than half a century, the interval was not unproductive of observations having an important bearing on the knowledge of the anatomy of the foetus and the function of reproduction. The great work of William Hunter on the human gravid uterus, containing unequalled pictorial illustrations of its subject from the pencil of Rymsdyk and other artists, was published in 1775;[3] and during a large part of the same period numerous communications to the Memoirs of the Royal Society testified to the activity and genius of his brother, John Hunter, in the investigation of various parts of comparative embryology. But it is mainly in his rich museum, and in the manuscripts and drawings which he left, and which have been in part described and published in the catalogue of his wonderful collection, that we obtain any adequate idea of the unexampled industry and wide scope of research of that great anatomist and physiologist.

As belonging to a somewhat later period, but still before the time when the more strict investigation of embryological phenomena was resumed by Pander, there fall to be noticed, as indicative of the rapid progress that was making, the experiments of L. Spallanzani, 1789; the researches of J. H. von Autenrieth, 1797, and of Soemmering, 1799, on the human foetus; the observations of Senff on the formation of the skeleton, 1801; those of L. Oken and D. G. Kieser on the intestine and other organs, 1806; Oken’s remarkable work on the bones of the head, 1807 (with the views promulgated in which Goethe’s name is also intimately connected); J. F. Meckel’s numerous and valuable contributions to embryology and comparative anatomy, extending over a long series of years; and F. Tiedemann’s classical work on the development of the brain, 1816.

The observations of the Russian naturalist, Christian Heinrich Pander (1794–1865), were made at the instance and under the immediate supervision of Prof. Döllinger at Würzburg, and we learn from von Baer’s autobiography that he, being an early friend of Pander’s, and knowing his qualifications for the task, had pointed him out to Döllinger as well fitted to carry out the investigation of development which that professor was desirous of having accomplished. Pander’s inaugural dissertation was entitled Historia metamorphoseos quam ovum incubatum prioribus quinque diebus subit (Virceburgi, 1817); and it was also published in German under the title of Beiträge zur Entwickelungsgeschichte des Hühnchens im Eie (Würzburg, 1817). The beautiful plates illustrating the latter work were executed by the elder E. J. d’Alton, well known for his skill in scientific observation, delineation and engraving.

Pander observed the germinal membrane or blastoderm, as he for the first time called it, of the fowl’s egg to acquire three layers of organized substance in the earlier period of incubation. These he named respectively the serous or outer, the vascular or middle, and the mucous or inner layers; and he traced with great skill and care the origin of the principal rudimentary organs and systems from each of these layers, pointing out shortly, but much more distinctly than Wolff had done, the actual nature of the changes occurring in the process of development.

Karl Ernest von Baer (q.v.), the greatest of modern embryologists, was, as already remarked, the early friend of Pander, and, at the time when the latter was engaged in his researches at Würzburg, was associated with Döllinger as prosector, and engaged with him in the study of comparative anatomy. He witnessed, therefore, though he did not actually take part in, Pander’s researches; and the latter having afterwards abandoned the inquiry, von Baer took it up for himself in the year 1819, when he had obtained an appointment in the university of Königsberg, where he was the colleague of Burdach and Rathke, both of whom were able coadjutors in the investigation of the subject of his choice. (See v. Baer’s interesting autobiography, published on his retirement from St Petersburg to Dorpat in 1864.)

Von Baer’s observations were carried on at various times from 1819 to 1826 and 1827, when he published the first results in a description of the development of the chick in the first edition of Burdach’s Physiology.

It was at this time that von Baer made the important discovery of the ovarian ovum of mammals and of man, totally unknown before his time, and was thus able to prove as matter of exact observation what had only been surmised previously, viz. the entire similarity in the mode of origin of these animals with others lower in the scale. (Epistola de ovi mammalium et hominis genesi, Lipsiae, 1827. See also the interesting commentary on or supplement to the Epistola in Heusinger’s Journal, and the translation in Breschet’s Répertoire, Paris, 1829.)

In 1829 von Baer published the first part of his great work, entitled Beobachtungen und Reflexionen über die Entwickelungsgeschichte der Thiere, the second part of which, still leaving the work incomplete, did not appear till 1838. In this work, distinguished by the fulness, richness and extreme accuracy of the observations and descriptions, as well as by the breadth and soundness of the general views on embryology and allied branches of biology which it presents, he gave a detailed account not only of the whole progress of development of the chick as observed day by day during the incubation of the egg, but he also described what was known, and what he himself had investigated by numerous and varied observations, of the whole course of formation of the young in other vertebrate animals. His work is in fact a system of comparative embryology, replete with new discoveries in almost every part.

Von Baer’s account of the layers of the blastoderm differs somewhat from that of Pander, and appears to be more consistent with the further researches which have lately been made than was at one time supposed, in this respect, that he distinguished from a very early period two primitive or fundamental layers, viz. the animal or upper, and the vegetative or lower, from each of which, in connexion with two intermediate layers derived from them, the fundamental organs and systems of the embryo are derived:—the animal layer, with its derivative, supplying the dermal, neural, osseous and muscular; the vegetative layer, with its derivative, the vascular and mucous (intestinal) systems. He laid down the general morphological principle that the fundamental organs have essentially the shape of tubular cavities, as appears in the first form of the central organ of the nervous system, in the two muscular and osseous tubes which form the walls of the body, and in the intestinal canal; and he followed out with admirable clearness the steps by which from these fundamental systems the other organs arise secondarily, such as the organs of sense, the glands, lungs, heart, vascular glands, Wolffian bodies, kidneys and generative organs.

To complete von Baer’s system there was mainly wanting a more minute knowledge of the intimate structure of the elementary tissues, but this had not yet been acquired by biologists, and it remained for Theodor Schwann of Liége in 1839, along with whom should be mentioned those who, like Robert Brown and M. J. Schleiden, prepared the way for his great discovery, to point out the uniformity in histological structure of the simpler forms of plants and animals, the nature of the organized animal and vegetable cell, the cellular constitution of the primitive ovum of animals, and the derivation of the various tissues, complex as well as simple, from the transformation or, as it is now called, differentiation of simple cellular elements,—discoveries which have exercised a powerful and lasting influence on the whole progress of biological knowledge in our time, and have contributed in an eminent degree to promote the advance of embryology itself.

To K. B. Reichert of Berlin more particularly is due the first application of the newer histological views to the explanation of the phenomena of development, 1840. To him and to R. A. von Kölliker and R. Virchow is due the ascertainment of the general principle that there is no free-cell formation in embryonic development and growth, but that all organs are derived from the multiplication, combination and transformation of cells, and that all cells giving rise to organs are the descendants or progeny of previously existing cells, and that these may be traced back to the original cell or cell-substance of the ovum.

It may be that modern research has somewhat modified the views taken by biologists of the statements of Schwann as to the constitution of the organized cell, especially as regards its simplest or most elementary form, and has indicated more exactly the nature of the protoplasmic material which constitutes its living basis; but it has not caused any very wide departure from the general principles enunciated by that physiologist. Schwann’s treatise, entitled Microscopical Researches into the Accordance in the Structure and Growths of Animals and Plants, was published in German at Berlin in 1839, and was translated into English by Henry Smith, and printed for the Sydenham Society in 1847, along with a translation of Schleiden’s memoir, “Contributions to Phytogenesis,” which originally appeared in 1838 in Müller’s Archiv for that year, and which had also been published in English in Taylor and Francis’s Scientific Memoirs, vol. ii. part vi.

Among the newer observations of the same period which contributed to a more exact knowledge of the structure of the ovum itself may be mentioned—first the discovery of the germinal vesicle, or nucleus, in the germ-disk of birds by J. E. von Purkinje (Symbolae ad ovi avium historiam ante incubationem, Vratislaviae, 1825, and republished at Leipzig in 1830); second, von Baer’s discovery of the mammiferous ovum in 1827, already referred to; third, the discovery of the germinal vesicle of mammals by J. V. Coste in 1834, and its independent observation by Wharton Jones in 1835; and fourth, the observation in the same year by Rudolph Wagner of the germinal macula or nucleus. Coste’s discovery of the germinal vesicle of Mammalia was first communicated to the public in the Comptes rendus of the French Academy for 1833, and was more fully described in the Recherches sur la génération des mammifères, by Delpech and Coste (Paris, 1834). Thomas Wharton Jones’s observations, made in the autumn of 1834, without a knowledge of Coste’s communication, were presented to the Royal Society in 1835. This discovery was also confirmed and extended by G. G. Valentin and Bernardt, as recorded by the latter in his work Symb. ad ovi mammal. hist. ante praegnationem. Rudolph Wagner’s observations first appeared in his Textbook of Comparative Anatomy, published at Leipzig in 1834–1835, and in Müller’s Archiv for the latter year. His more extended researches are described in his work Prodromus hist. generationis hominis atque animalium (Leipzig, 1836), and in a memoir inserted in the Trans. of the Roy. Bavarian Acad. of Sciences (Munich, 1837).

The two decades of years from 1820 to 1840 were peculiarly fertile in contributions to the anatomy of the foetus and the progress of embryological knowledge. The researches of Prévost and Dumas on the ova and primary stages of development of Batrachia, birds and mammals, made as early as 1824, deserve especial notice as important steps in advance, both in the discovery of the process of yolk segmentation in the batrachian ovum, and in their having shown almost with the force of demonstration, previous to the discovery of the mammiferous ovarian ovum by von Baer, that that body must exist as a minute spherule in the Graafian follicle of the ovary, although they did not actually succeed in bringing the ova clearly under observation.

The works of Pockels (1825), of Seiler (1831), of G. Breschet (1832), of A. A. L. M. Velpeau (1833), of T. L. W. Bischoff (1834)—all bearing upon human embryology; the researches of Coste in comparative embryology in 1834, already referred to, and those published by the same author in 1837; the publication of Johannes Müller’s great work on physiology, and Rudolph Wagner’s smaller text-book, in both of which the subject of embryology received a very full treatment, together with the excellent Manual of the Development of the Foetus, by Valentin, in 1835, the first separate and systematic work on the whole subject, now secured to embryology its permanent place among the biological sciences on the Continent; while in this country attention was drawn to the subject by the memoirs of Allen Thomson (1831), Th. Wharton Jones (1835–1838) and Martin Barry (1839–1840).

Among the more remarkable special discoveries which belong to the period now referred to, a few may be mentioned, as, for example, that of the chorda dorsalis by von Baer, a most important one, which may be regarded as the key to the whole of vertebral morphology; the phenomenon of yolk segmentation, now known to be universal among animals, but which was only first carefully observed in Batrachia by Prévost and Dumas (though previously casually noticed by Swammerdam), and was soon afterwards followed out by Rusconi and von Baer in fishes; the discovery of the branchial clefts, plates and vascular arches in the embryos of the higher abranchiate animals by H. Rathke in 1825–1827; the able investigation of the transformations of these arches by Reichert in 1837; and the researches on the origin and development of the urinary and generative organs by Johannes Müller in 1829–1830.

On entering the fifth decade of the 19th century, the number of original contributions and systematic treatises becomes so great as to render the attempt to enumerate even a selection of the more important of them quite unsuitable to the limits of the present article. We must be satisfied, therefore, with a reference to one or two which seem to stand out with greater prominence than the rest as landmarks in the progress of embryological discovery. Among these may first be mentioned the researches of Theodor L. W. von Bischoff, formerly of Giessen and later of Munich, on the development of the ovum in Mammalia, in which a series of the most laborious, minute and accurate observations furnished a greatly novel and very full history of the formative process in several animals of that class. These researches are contained in four memoirs, treating separately of the development of the rabbit, the dog, the guinea-pig and the roe-deer, and appeared in succession in the years 1842, 1845, 1852 and 1854.

Next may be mentioned the great work of Coste, entitled Histoire gén. et particul. du développement des animaux, of which, however, only four fasciculi appeared between the years 1847 and 1859, leaving the work incomplete. In this work, in the large folio form, beautiful representations are given of the author’s valuable observations on human embryology, and on that of various mammals, birds and fishes, and of the author’s discovery in 1847 of the process of partial yolk segmentation in the germinal disk of the fowl’s egg during its descent through the oviduct, and his observations on the same phenomenon in fishes and mammals.

The development of reptiles received important elucidation from the researches of Rathke, in his history of the development of serpents, published at Königsberg in 1839, and in a similar work on the turtle in 1848, as well as in a later one on the crocodile in 1866, along with which may be associated the observations of H. J. Clark on the “Embryology of the Turtle,” published in Agassiz’s Contributions to Natural History, &c., 1857.

The phenomena of yolk segmentation, to which reference has more than once been made, and to which later researches give more and more importance in connexion with the fundamental phenomena of development, received great elucidation during this period, first from the observations of C. T. E. von Siebold and those of Bagge on the complete yolk segmentation of the egg in nematoid worms in 1841, and more fully by the observations of Kölliker in the same animals in 1843. The nature of partial segmentation of the yolk was first made known by Kölliker in his work on the development of the Cephalopoda in 1844, and, as has already been mentioned, the phenomena were observed by Coste in the eggs of birds. The latter observations have since been confirmed by those of Oellacher, Götte and Kölliker. Further researches in a vast number of animals give every reason to believe that the phenomenon of segmentation is in some shape or other the invariable precursor of embryonic formation.

The first considerable work on the development of a division of the invertebrates was that of Maurice Herold of Marburg on spiders, De generatione aranearum ex ovo, published at Marburg in 1824, in which the whole phenomena of the formative processes in that animal are described with remarkable clearness and completeness. A few years later an important series of contributions to the history of the development of invertebrate animals appeared in the second volume of Burdach’s work on Physiology, of which the first edition was published in 1828, and in this the history of the development of the Entozoa was the production of Ch. Theod. von Siebold, and that of most of the other invertebrates was compiled by H. Rathke from the results of his own observations and those of others. These memoirs, together with others subsequently published by Rathke, notably that Über die Bildung und Entwickelungsgeschichte d. Flusskrebses (Leipzig, 1829), in which an attempt is made to extend the doctrine of the derivation of the organs from the germinal layers to the invertebrata, entitle him to be regarded as the founder of invertebrate embryology.

A large body of facts having by this time been ascertained with respect to the more obvious processes of development, a further attempt to refer the phenomena of organogenesis to morphological and histological principles became desirable. More especially was the need felt to point out with greater minuteness and accuracy the relation in which the origin of the fundamental organs of the embryo stands to the layers of the blastoderm; and this we find accomplished with signal success in the researches of R. Remak on the development of the chick and frog, published between the years 1850 and 1855.

Starting from Pander’s discovery of the trilaminate blastoderm, Remak worked out the development of the chick in the light of the cell-theory of Schleiden and Schwann. He observed the division of the middle layer into two by a split which subsequently gives rise to the body-cavity (pleuro-peritoneal space) of the adult; and traced the principal organs which came from these two layers (Hautfaserblatt and Darmfaserblatt) respectively. In this manner the foundations of the germ-layer theory were established in their modern form.

A great step forward was made in 1859 by T. H. Huxley, who compared the serous and mucous layers of Pander with the ectoderm and endoderm of the Coelenterata. But in spite of this comparison it was generally held that germinal layers similar to those of the vertebrata were not found in invertebrate animals, and it was not until the publication in 1871 of Kowalewsky’s researches (see below) that the germinal layer theory was applied to the embryos of all the Metazoa. But the year 1859 will be for ever memorable in the history of science as the year of the publication of the Origin of Species. If the enunciation of the cell-theory may be said to have marked a first from a second period in the history of embryology, the publication of Darwin’s great idea ushered in a third. Whereas hitherto the facts of anatomy and development were loosely held together by the theory of types which owed its origin and maintenance to Cuvier, L. Agassiz, J. Müller and R. Owen, they were now combined into one organic whole by the theory of descent and by the hypothesis of recapitulation which was deduced from that theory. First clearly enunciated by Johann Müller in his well-known work Für Darwin published in 1864 (rendered in England as Facts for Darwin, 1869), the view that a knowledge of embryonic and larval histories would lay bare the secrets of race history and enable the course of evolution to be traced and so lead to the discovery of the natural system of classification, gave a powerful stimulus to embryological research. The first fruits of this impetus were gathered by Alexander Agassiz, A. Kowalewsky and E. Metschnikoff. Agassiz, in his memoir on the Embryology of the Starfish published in 1864, showed that the body-cavity in Echinodermata arises as a differentiation of the enteron of the larva and so laid the foundations of our present knowledge of the coelom. This discovery was confirmed in 1869 by Metschnikoff (“Studien üb. d. Entwick. d. Echinodermen u. Nemertinen,” Mém. Ac. Pétersbourg (7), 41, 1869), and extended by him to Tornaria, the larva of Balanoglossus in 1870 (“Untersuchungen üb. d. Metamorphose einiger Seethiere,” Zeit. f. wiss. Zoologie, 20, 1870). In 1871 Kowalewsky in his classical memoir, entitled “Embryologische Studien an Würmern und Arthropoden” (Mém. Acad. Pétersbourg (7), 16, 1871), proved the same fact for Sagitta and added immensely to our knowledge of the early stages of development of the Invertebrata. These memoirs formed the basis on which subsequent workers took their stand. Amongst the most important of these was F. M. Balfour (1851–1882). Led to the study of embryology by his teacher, M. Foster, in association with whom he published in 1874 the Elements of Embryology, Balfour was one of the first to take advantage of the facilities for research offered by Dr. A. Dohrn’s Zoological Station at Naples which has since become so celebrated. Here he did the work which was subsequently published in 1878 in his Monograph of the Development of Elasmobranch Fishes, and which constituted the most important addition to vertebrate morphology since the days of Johannes Müller. This was followed in 1879 and 1881 by the publication of his Treatise on Comparative Embryology, the first work in which the facts of the rapidly growing science were clearly and philosophically put together, and the greatest. The influence of Balfour’s work on embryology was immense and is still felt. He was an active worker in every department of it, and there are few groups of the animal kingdom on which he has not left the impress of his genius.

In the period under consideration the output of embryological work has been enormous. No group of the animal kingdom has escaped exhaustive examination, and no effort has been spared to obtain the embryos of isolated and out of the way forms, the development of which might have a bearing upon important questions of phylogeny and classification. Of this work it is impossible to speak in detail in this summary. It is only possible to call attention to some of its more important features, to mention the more important advances, and to refer to some of the more striking memoirs.

Marine zoological stations have been established, expeditions have been sent to distant countries, and the methods of investigation have been greatly improved. Since Anton Dohrn founded the Stazione Zoologica at Naples in 1872, observatories for the study of marine organisms have been established in most countries. Of journeys which have been made to distant countries and which have resulted in important contributions to embryology, may be mentioned the expedition (1884–1886) of the cousins Sarasin to Ceylon (development of Gymnophiona), of E. Selenka to Brazil and the East Indies (development of Marsupials, Primates and other mammals, 1877, 1889, 1892), of A. A. W. Hubrecht to the East Indies (1890, development of Tarsius), of W. H. Caldwell to Australia (1883–1884, discovery of the nature of the ovum and oviposition of Echidna and of Ceratodus), of A. Sedgwick to the Cape (1883, development of Peripatus), of J. Graham Kerr to Paraguay (1896, development of Lepidosiren), of R. Semon to Australia and the Malay Archipelago (1891–1893, development of Monotremata, Marsupialia), and of J. S. Budgett to Africa (1898, 1900, 1901, 1903, development of Polypterus).

In methods, while great improvements have been made in the processes of hardening and staining embryos, the principal advance has been the introduction in 1883 by W. H. Caldwell in his work on the development of Phoronis of the method of making tape-worm like strings of sections as a result of which the process of mounting in order all the sections obtained from an embryo was much facilitated, and the use of an automatic microtome rendered possible. The method of Golgi for the investigation of the nervous system, introduced in 1875, must also be mentioned here.

The word “coelom” (q.v.) was introduced into zoology by E. Haeckel in 1872 (Kalkschwämme, p. 468) as a convenient term for the body-cavity (pleuro-peritoneal). The word was generally adopted, and was applied alike to the blood-containing body-cavity of Arthropods and to the body-cavity of Vertebrata and segmented worms, in which there is no blood. In 1875 Huxley (Quarterly Journ. of Mic. Science, 15, p. 53), relying on the researches of Agassiz, Metschnikoff and Kowalewsky above mentioned, put forward the idea that according to their development three kinds of body-cavity ought to be distinguished: (1) the enterocoelic which arises from enteric diverticula, (2) the schizocoelic which develops as a split in the embryonic mesoblast, and (3) the epicoelic which was enclosed by folds of the skin and lined by ectoderm (e.g. atrial cavity of Tunicates, &c.). This suggestion was of great importance, because it led the embryologists of the day (Balfour, the brothers Hertwig, Lankester and others) to discuss the question as to whether there was not more than one kind of body-cavity. The Hertwigs (Coelomtheorie, Jena, 1881) distinguished two kinds, the enterocoel and the pseudocoel. The former, to which they limited the use of the word coelom, and which is developed directly or indirectly from the enteron, is found in Annelida, Arthropoda, Echinodermata, Chordata, &c. The latter they regarded as something quite different from the coelom and as arising by a split in what they called for the first time mesenchyme; the mesenchyme being the non-epithelial mesoderm, which they described as consisting of amoeboid cells, but which we now know to consist of a continuous reticulum. The next step was made by E. Ray Lankester, who in 1884 (Zoologischer Anzeiger) showed that the pericardium of Mollusca does not contain blood, and therein differs from the rest of the body-cavity which does contain blood, but no suggestion is made that the blood-containing space is not coelomic. In fact it was generally held by the anatomists of the day that the coelom and the vascular system were different parts of the same primitive organ, though separate from it in the adult except in Arthropoda and Mollusca. In the Mollusca, it is true, the pericardial part of the coelom was held to be separate from the vascular, and the Hertwigs had reached the correct conception that the pericardium of these animals was alone true coelom, the vascular part being pseudocoel. This was the state of morphological opinion until 1886, when it was shown (Proc. Cambridge Phil. Soc., 6, 1886, p. 27) (1) that the coelom of Peripatus gives rise to the nephridia and generative glands only, and to no other part of the body-cavity of the adult, (2) that the nephridia of the adult do not open as had been supposed into the body-cavity, (3) that the body-cavity is entirely formed of the blood-containing space, the coelom having no perivisceral portion. These results were extended by the same author (Quart. Journ. Mic. Sci., 27, 1887, pp. 486-540) to other Arthropods and to the Mollusca, and the modern theory of the coelom was finally established. An increased precision was given to the conception of coelom by the discovery in 1880 (Quart. Journ. Mic. Sci., 20, p. 164) that the nephridia of Elasmobranchs are a direct differentiation of a portion of it. In 1886 this was extended to Peripatus (Proc. Camb. Phil. Soc., 6, p. 27) and doubtless holds universally.

In 1864 it was suggested by V. Hensen (Virchow’s Archiv, 31) that the rudiments of nerve-fibres are present from the beginning of development as persistent remains of connexions between the incompletely separated cells of the segmented ovum. This suggestion fell to the ground because it was held by embryologists that the cleavage of the ovum resulted in the formation of completely separate cells, and that the connexions between the adult cells were secondary. In 1886 it was shown (Quarterly Journ. Mic. Sci., 26, p. 182) that in Peripatus Capensis the cells of the segmenting ovum do not separate from one another, but remain connected by a loose protoplasmic network. This discovery has since been extended to other ova, even to the small so-called holoblastic ova, and a basis of fact was found for Hensen’s suggestion as to the embryonic origin of nerves (Quart. Journ. Mic. Sci., 33, 1892, pp. 581-584). An extension and further application of the new views as to the cell-theory and the embryonic origin of nerves thus necessitated was made in 1894 (Quart. Journ. Mic. Sci., 37, p. 87), and in 1904 J. Graham Kerr showed that the motor nerves in the dipnoan fish Lepidosiren arise in an essentially similar manner (Trans. Roy. Society of Edinburgh, 41, p. 119).

In 1883 Elie Metschnikoff published his researches on the intracellular digestion of invertebrates (Arbeiten a. d. zoologischen Inst. Wien, 5; and Biologisches Centralblatt, 3, p. 560); these formed the basis of his theory of inflammation and phagocytosis, which has had such an important influence on pathology. As he himself has told us, he was led to make these investigations by his precedent researches on the development of sponges and other invertebrates. To quote his own words: “Having long studied the problem of the germinal layers in the animal series, I sought to give some idea of their origin and significance. The part played by the ectoderm and endoderm appeared quite clear, and the former might reasonably be regarded as the cutaneous investment of primitive multicellular animals, while the latter might be regarded as their organ of digestion. The discovery of intracellular digestion in many of the lower animals led me to regard this phenomenon as characteristic of those ancestral animals from which might be derived all the known types of the animal kingdom (excepting, of course, the Protozoa). The origin and part played by the mesoderm appeared the most obscure. Thus certain embryologists supposed that this layer corresponded to the reproductive organs of primitive animals: others regarded it as the prototype of the organs of locomotion. My embryological and physiological studies on sponges led me to the conclusion that the mesoderm must function in the hypothetically primitive animals as a mass of digestive cells, in all points similar to those of the endoderm. This hypothesis necessarily attracted my attention to the power of seizing foreign corpuscles possessed by the mesodermic cells” (Immunity in Infective Diseases, English translation, Cambridge, 1905).

The branch of embryology which concerns itself with the study of the origin, history and conjugation of the individuals (gametes) which are concerned in the reproduction of the species has made great advances. These began in 1875 and following years with a careful examination of the behaviour of the germinal vesicle in the maturation and fertilization of the ovum. The history of the polar bodies, the origin of the female pronucleus, the presence in the ovum of a second nucleus, the male pronucleus, which gave rise to the first segmentation nucleus by fusion with the female pronucleus, were discovered (E. van Beneden, O. Bütschli, O. Hertwig, H. Fol), and in 1876 O. Hertwig (Morphologisches Jahrbuch, 3, 1876) for the first time observed the entrance of a spermatozoon into the egg and the formation of the male pronucleus from it. The centrosome was discovered by W. Flemming in 1875 in the egg of the fresh-water mussel, and independently in 1876 by E. van Beneden in Dicyemids. In 1883 came E. van Beneden’s celebrated discovery (Arch. Biologie, 4) of the reduction of the number of chromosomes in the nucleus of both male and female gametes, and of the fact that the male and female pronuclei contribute the same number of chromosomes to the zygote-nucleus. He also showed that the gametogenesis in the male is a similar process to that in the female, and paved the way for the acceptation of the view (due to Bütschli) that polar bodies are aborted female gametes. These discoveries were extended and completed by subsequent workers, among whom may be mentioned E. van Beneden, J. B. Carnoy, G. Platner, T. Boveri, O. Hertwig, A. Brauer. The subject is still being actively pursued, and hopes are entertained that some relation may be found between the behaviour of the chromosomes and the facts of heredity.

Since 1874 (W. His, Unsere Körperform und das physiologische Problem ihrer Entstehung) a new branch of embryology, which concerns itself with the physiology of development, has arisen (experimental embryology). The principal workers in this field have been W. Roux, who in 1894 founded the Archiv für Entwickelungsmechanik der Organismen, T. Boveri and Y. Delage who discovered and elucidated the phenomenon of merogony, J. Loeb who discovered artificial parthenogenesis, O. and R. Hertwig, H. Driesch, C. Herbst, E. Maupas, A. Weismann, T. H. Morgan, C. B. Davenport (Experimental Morphology, 2 vols., 1899) and many others.

In the elucidation of remarkable life-histories we may point in the first place to the work of A. Kowalewsky on the development of the Tunicata (“Entwickelungsgeschichte d. einfachen Ascidien,” Mém. Acad. Pétersbourg (7), 10, 1866, and Arch. f. Mic. Anatomie, 7, 1871), in which was demonstrated for the first time the vertebrate relationship of the Tunicata (possession of a notochord, method of development of the central nervous system) and which led to the establishment of the group Chordata. We may also mention the work of Y. Delage in the metamorphosis of Sacculina (Arch. zool. exp. (2) 2, 1884), A. Giard (Comptes rendus, 123, 1896, p. 836) and of A. Malaquin on Monstrilla (Arch. zool. exp. (3), 9, p. 81, 1901), of Delage (Comptes rendus, 103, 1886, p. 698) and Grassi and Calandruccio (Rend. Acc. Lincei (5), 6, 1897, p. 43), on the development of the eels, and of P. Pergande on the life-history of the Aphidae (Bull. U.S. Dep. Agric. Ent., technical series, 9, 1901). The work of C. Grobben (Arbeiten zool. Inst. Wien, 4, 1882) and of B. Uljanin (“Die Arten der Gattung Doliolum,” Fauna u. Flora des Golfes von Neapel, 1884) on the extraordinary life-history and migration of the buds in Doliolum must also be mentioned. In pure embryological morphology we have had Heymons’ elucidation of the Arthropod head, the work of Hatschek on Annelid and other larvae, the works of H. Bury and of E. W. MacBride which have marked a distinct advance in our knowledge of the development of Echinodermata, of K. Mitsukuri, who has founded since 1882 an important school of embryology in Japan, on the early development of Chelonia and Aves, of A. Brauer and G. C. Price on the development of vertebrate excretory organs, of Th. W. Bischoff, E. van Beneden, E. Selenka, A. A. W. Hubrecht, R. Bonnet, F. Keibel and R. Assheton on the development of mammals, of A. A. W. Hubrecht and E. Selenka on the early development and placentation of the Primates, of J. Graham Kerr and of J. S. Budgett on the development of Dipnoan and Ganoid fishes, of A. Kowalewsky, B. Hatschek, A. Willey and E. W. MacBride on the development of Amphioxus, of B. Dean on the development of Bdellostoma, of A. Götte on the development of Amphibia, of H. Strahl and L. Will on the early development of reptiles, of T. H. Huxley, C. Gegenbaur and W. K. Parker on the development of the vertebrate skeleton, of van Wijhe on the segmentation of the vertebrate head, by which the modern theory of head-segmentation, previously adumbrated by Balfour, was first established, of Leche and Röse on the development of mammalian dentitions. We may also specially notice W. Bateson’s work on the development of Balanoglossus and his inclusion of this genus among the Chordata (1884), the discovery by J. P. Hill of a placenta in the marsupial genus Perameles (1895), the work of P. Marchal (1904) on the asexual increase by fission of the early embryos of certain parasitic Hymenoptera (so called germinogony), a phenomenon which had been long ago shown to occur in Lumbricus trapezoides by N. Kleinenberg (1879) and by S. F. Harmer in Polyzoa (1893). The work on cell-lineage which has been so actively pursued in America may be mentioned here. It has consisted mainly of an extension of the early work of A. Kowalewsky and B. Hatschek on the formation of the layers, being a more minute and detailed examination of the origin of the embryonic tissues.

The most important text-books and summaries which have appeared in this period have been Korschelt and Heider’s Lehrbuch der vergleichenden Entwickelungsgeschichte der wirbellosen Tiere (1890–1902), C. S. Minot’s Human Embryology (1892), and the Handbuch der vergleichenden und experimentellen Entwickelungslehre der Wirbeltiere, edited by O. Hertwig (1901, et seq.). See also K. E. von Baer, Über Entwicklungsgeschichte der Tiere (Königsberg, 1828, 1837); F. M. Balfour, A Monograph on the Development of Elasmobranch Fishes (London, 1878); A Treatise on Comparative Embryology, vols. i. and ii. (London, 1885) (still the most important work on Vertebrate Embryology); M. Duval, Atlas d’Embryologie (Paris, 1889); M. Foster and F. M. Balfour, Elements of Embryology (London, 1883); O. Hertwig, Lehrbuch der Entwicklungsgeschichte des Menschen u. der Wirbeltiere (6th ed., Jena, 1898); A. Kölliker, Entwicklungsgeschichte des Menschen u. der höheren Tiere (Leipzig, 1879); A. M. Marshall, Vertebrate Embryology (London, 1893).  (A. Se.*) 

Physiology of Development

Physiology of Development [in German, Entwicklungsmechanik (W. Roux), Entwicklungsphysiologie (H. Driesch), physiologische Morphologie (J. Loeb)] is, in the broadest meaning of the word, the experimental science of morphogenesis, i.e. of the laws that govern morphological differentiation. In this sense it embraces the study of regeneration and variation, and would, as a whole, best be called rational morphology. Here we shall treat of the Physiology of Development in a narrower sense, as the study of the laws that govern the development of the adult organism from the egg, Regeneration and Variation and Selection forming the subjects of special articles.

After the work done by W. His, A. Goette and E. F. W. Pflüger, who gave a sort of general outline and orientation of the subject, the first to study developmental problems properly in a systematical way, and with full conviction of their great importance, was Wilhelm Roux. This observer, having found by a full analysis of the facts of “development” that the first special problem to be worked out was the question when and where the first differentiation appeared, got as his main result that, when one of the two first blastomeres (cleavage cells) of the frog’s egg was killed, the living one developed into a typical half-embryo, i.e. an embryo that was either the right or the left part of a whole one. From that Roux concluded that the first cleavage plane determined already the median plane of the adult; and that the basis of all differentiation was given by an unequal division of the nuclear substances during karyokinesis, a result that was also attained on a purely theoretical basis by A. Weismann. Hans Driesch repeated Roux’s fundamental experiment with a different method on the sea-urchin’s egg, with a result that was absolutely contrary to that of Roux: the isolated blastomere cleaved like half the egg, but it resulted in a whole blastula and a whole embryo, which differed from a normal one only in its small size. Driesch’s result was obtained in somewhat the same manner by E. B. Wilson with the egg of Amphioxus, by Zoja with the egg of Medusae, &c. It thus became very probable that an inequality of nuclear division could not be the basis of differentiation. The following experiments were still more fatal to the theories of Roux and of Weismann. Driesch found that even when the first eight or sixteen cells of the cleaving egg of the sea-urchin were brought into quite abnormal positions with regard to one another, still a quite normal embryo was developed; Driesch and T. H. Morgan discovered jointly that in the Ctenophore egg one isolated blastomere developed into a half-embryo, but that the same was the case if a portion of protoplasm was cut off from the fertilized egg not yet in cleavage; last, but not of least importance, in the case of the frog’s egg which had been Roux’s actual subject of experiment, conditions were discovered by O. Schultze and O. Hertwig under which one of the two first blastomeres of this egg developed into a whole embryo of half size. This result was made still more decisive by Morgan, who showed that it was quite in the power of the experimenter to get either a half-embryo or a whole one of half size, the latter dependent only upon giving to the blastomere the opportunity for a rearrangement of its matter by turning it over.

Thus we may say that the general result of the introductory series of experiments in the physiology of development is the following:—In many forms, e.g. Echinoderms, Amphioxus, Ascidians, Fishes and Medusae, the potentiality (prospective Potenz—Driesch) of all the blastomeres of the segmented egg is the same, i.e. each of them may play any or every part in the future development; the prospective value (prosp. Bedeutung—D.) of each blastomere depends upon, or is a function of, its position in the whole of the segmented egg; we can term the “whole” of the egg after cleavage an “aequipotential system” (Driesch). But though aequipotential, the whole of the segmented egg is nevertheless not devoid of orientation or direction; the general law of causality compels us to assume a general orientation of the smallest parts of the egg, even in cases where we are not able to see it. It has been experimentally proved that external stimuli (light, heat, pressure, &c.) are not responsible for the first differentiation of organs in the embryo; thus, should the segmented egg be absolutely equal in itself, it would be incomprehensible that the first organs should be formed at one special point of it and not at another. Besides this general argument, we see a sort of orientation in the typical forms of the polar or bilateral cleavage stages.

Differentiation, therefore, depends on a primary, i.e. innate, orientation of the egg’s plasma in those forms, the segmented eggs of which represent aequipotential systems; this orientation is capable of a sort of regulation or restoration after disturbances of any sort; in the egg of the Ctenophora such a regulation is not possible, and in the frog’s egg it is facultative, i.e. possible under certain conditions, but impossible under others. Should this interpretation be right, the difference between the eggs of different animals would not be so great as it seemed at first: differences with regard to the potentialities of the blastomeres would only be differences with regard to the capability of regulation or restoration of the egg’s protoplasm.

The foundation of physiological embryology being laid, we now can shortly deal with the whole series of special problems offered to us by a general analysis of that science, but at present worked out only to a very small extent.

We may ask the following questions:—What are the general conditions of development? On what general factors does it depend? How do the different organs of the partly developed embryo stand with regard to their future fate? What are the stimuli (Reize) effecting differentiation? What is to be said about the specific character of the different formative effects? And as the most important question of all: Are all the problems offered to us in the physiology of development to be solved with the aid of the laws known hitherto in science, or do we want specifically new “vitalistic” factors?

Energy in different forms is required for development, and is provided by the surrounding medium. Light, though of no influence on the cleavage (Driesch), has a great effect on later stages of development, and is also necessary for the formation of polyps in Eudendrium (J. Loeb). Conditions of differentiation. That a certain temperature is necessary for ontogeny has long been known; this was carefully studied by O. Hertwig, as was also the influence of heat on the rate of development. Oxygen is also wanted, either from a certain stage of development or from the very beginning of it, though very nearly related forms differ in this respect (Loeb). The great influence of osmotic pressure on growth was studied by J. Loeb, C. Herbst and C. H. Davenport. In all these cases energy may be necessary for development in general, or a specific form of energy may be necessary for the formation of a specific organ; it is clear that, especially in the latter case, energy is shown to be a proper factor for morphogenesis. Besides energy, a certain chemical condition of the medium, whether offered by the water in which the egg lives or (especially in later stages) by the food, is of great importance for normal ontogeny; the only careful study in this respect was carried out by Herbst for the development of the egg of Echinids. This investigator has shown that all salts of the sea water are of great importance for development, and most of them specifically and typically; for instance, calcium is absolutely necessary for holding together the embryonic cells, and without calcium all cells will fall apart, though they do not die, but live to develop further.

What we have dealt with may be called external factors of development; as to their complement, the internal factors, it is clear that every elementary factor of general physiology may be regarded as one of them. Chemical metamorphosis plays, of course, a great part in differentiation, especially in the form of secretions; but very little has been carefully studied in this respect. Movement of living matter, whether of cells or of intracellular substance, is another important factor (O. Bütschli, F. Dreyer, L. Rhumbler.) Cell-division is another, its differences in direction, rate and quantity being of great importance for differentiation. We know very little about it; a so-called law of O. Hertwig, that a cell would divide at right angles to its longest diameter, though experimentally stated in some cases, does not hold for all, and the only thing we can say is, that the unknown primary organization of the egg is here responsible. (Compare the papers on “cell-lineage” of E. B. Wilson, F. R. Lillie, H. S. Jennings, O. Zurstrassen and others.) Of the inner factors of ontogeny there is another category that may be called physical, that already spoken of being physiological. The most important of these is the capillarity of the cell surfaces. Berthold was the first to call attention to its role in the arrangement of cell composites, and afterwards the matter was more carefully studied by Dreyer, Driesch, and especially W. Roux, with the result that the arrangement of cells follows the principle of surfaces minimae areae (Plateau) as much as is reconcilable with the conditions of the system.

It has already been shown that in many cases the embryo after cleavage, i.e. the blastula, is an “aequipotential system.” It was shown that in the egg of Echinids there existed such an absolute lack of determination of the cleavage cells that (a) the cells may be put in quite abnormal Potentialities of embryonic cells. positions with reference to one another without disturbing development; (b) a quarter blastomere gives a quite normal little pluteus, even a sixteenth yields a gastrula; (c) two eggs may fuse in the early blastula stage, giving one single normal embryo of double size. Our next question concerns the distribution of potentiality, when the embryo is developed further than the blastula stage. In this case it has been shown that the potentialities of the different embryonic organs are different: that, for instance, in Echinoderms or Amphibians the ectoderm, when isolated, is not able to form endoderm, and so on (Driesch, D. Barfurth); but it has been shown at the same time that the ectoderm in itself, the intestine in itself of Echinoderms (Driesch), the medullary plate in itself of Triton (H. Spemann), is as aequipotential as was the blastula: that any part whatever of these organs may be taken away without disturbing the development of the rest into a normal and proportional embryonic part, except for its smaller size.

If the single phases of differentiation are to be regarded as effects, we must ask for the causes, or stimuli, of these effects. For a full account of the subject we refer to Herbst, by whom also the whole botanical literature, much more important than the zoological, is critically reviewed. Formative stimuli. We have already seen that when the blastula represents an aequipotential system, there must be some sort of primary organization of the egg, recoverable after disturbances, that directs and localizes the formation of the first embryonic organs; we do not know much about this organization. Directive stimuli (Richtungsreize) play a great role in ontogeny; Herbst has analysed many cases where their existence is probable. They have been experimentally proved in two cases. The chromatic cells of the yolk sac of Fundulus are attracted by the oxygen of the arteriae (Loeb); the mesenchyme cells of Echinus are attracted by some specific parts of the ectoderm, for they move towards them also when removed from their original positions to any point of the blastocoel by shaking (Driesch). Many directive stimuli might be discovered by a careful study of grafting experiments, such as have been made by Born, Joest, Harrison and others, but at present these experiments have not been carried out far enough to get exact results.

Formative stimuli in a narrower meaning of the word, i.e. stimuli affecting the origin of embryonic organs, have long been known in botany; in zoology we know (especially from Loeb) a good deal about the influence of light, gravitation, contact, &c., on the formation of organs in hydroids, but these forms are very plant-like in many respects; as to free-living animals, Herbst proved that the formation of the arms of the pluteus larva depends on the existence of the calcareous tetrahedra, and made in other cases (lens of vertebrate eye, nerves and muscles, &c.) the existence of formative stimuli very probable. Many of the facts generally known as functional adaptation (functionelle Anpassung—Roux) in botany and zoology may also belong to this category, i.e. be the effects of some external stimulus, but they are far from having been analysed in a satisfactory manner. That the structure of parts of the vertebrate skeleton is always in relation to their function, even under abnormal conditions, is well known; what is the real “cause” of differentiation in this case is difficult to say.

It is obvious that we cannot answer the question why the different ontogenetic effects are just what they are. Developmental physiology takes the specific nature of form for granted, and it may be left for a really rational theory of the evolution of species in the future to answer Specific characters. the problem of species, as far as it is answerable at all. What we intend to do here is only to say in a few words wherein consists the specific character of embryonic organs. That embryonic parts are specific or typical in regard to their protoplasm is obvious, and is well proved by the fact that the different parts of the embryo react differently to the same chemical or other reagents (Herbst, Loeb). That they may be typical also in regard to their nuclei was shown by Boveri for the generative cells of Ascaris; we are not able at present to say anything definite about the importance of this fact. The specific nature of an embryonic organ consists to a high degree in the number of cells composing it; it was shown for many cases that this number, and also the size of cells, is constant under constant conditions, and that under inconstant conditions the number is variable, the size constant; for instance, embryos which have developed from one of the two first blastomeres show only half the normal number of cells in their organs (Morgan, Driesch).

We have learnt that the successive steps of embryonic development are to be regarded as effects, caused by stimuli, which partly exist in the embryo itself. But it must be noted that not every part of the embryo is dependent on every other one, but that there exists a great independence Self-differentiation. of the parts, to a varying degree in every case. This partial independence has been called self-differentiation (Selbstdifferenzierung) by Roux, and is certainly a characteristic feature of ontogeny. At the same time it must not be forgotten that the word is only relative, and that it only expresses our recognition of a negation.

For instance, we know that the ectoderm of Echinus may develop further if the endoderm is taken away; in other words, that it develops by self-differentiation in regard to the endoderm, that its differentiation is not dependent on the endoderm; but it would be obviously more important to know the factors on which this differentiation is actually dependent than to know one factor on which it is not. The same is true for all other experiments on “self-differentiation,” whether analytical (Loeb, Schaper, Driesch) or not (grafting experiments, Born, Joest, &c.).

Can we understand differentiation by means of the laws of natural phenomena offered to us by physics and chemistry? Most people would say yes, though not yet. Driesch has tried to show that we are absolutely not able to understand development, at any rate one part of it, i.e. the Vitalism. localization of the various successive steps of differentiation. But it is impossible to give any idea of this argument in a few words, and we can only say here that it is based on the experiments upon isolated blastomeres, &c., and on an analysis of the character of aequipotential systems. In this way physiology of development would lead us straight on into vitalism.

References.—An account of the subject, with full literature, is given by H. Driesch, Resultate und Probleme der Entwicklungsphysiologie der Tiere in Ergebnissen der Anat. u. Entw.-Gesch. (1899). Other works are: C. H. Davenport, Experimental Morphology (New York, 1897–1899); Y. Delage, La Structure du protoplasma, &c. (1895); Driesch, Mathem. mech. Betrachtung morpholog. Probleme (Jena, 1891); Entwicklungsmechan. Studien (1891–1893); Analytische Theorie d. organ. Entw. (Leipzig, 1894); Studien über d. Regulationsvermögen (1897–1900), &c.; C. Herbst, “Über die Bedeutung d. Reizphysiologie für die kausale Auffassung von Vorgängen i. d. tier. Ontogenese,” Biolog. Centralblatt, vols. xiv. u. xv. (Leipzig, 1894). Many papers on influence of salts on development in Arch. f. Entw.-Mech.; O. Hertwig, Papers in Arch. f. mikr. Anat., “Die Zelle und die Gewebe,” ii. (Jena, 1897); W. His, Unsere Körperform (Leipzig, 1875); J. Loeb, Untersuch. z. physiol. Morph. (Würzburg, 1891–1892). Papers in Arch. f. Entw.-Mech. and Pflüger’s Archiv; T. H. Morgan, The Development of the Frog’s Egg (New York, 1897); Papers in Arch. f. Entw.-Mech.; Roux, Gesammelte Abhandlungen (Leipzig, 1895); Papers in Arch. f. Entw.-Mech.; A. Weismann, Das Keimplasma (Jena, 1892); E. B. Wilson, papers in Journ. Morph., “The Cell in Development and Inheritance” (New York, 1896).  (H. A. E. D.) 


  1. In the mammalia the word foetus is often employed in the same signification as embryo; it is especially applied to the embryo in the later stages of uterine development.
  2. It may be proper to mention, as authors of this period who made special researches on the development of the embryo—(1) Volcher Coiter of Groningen, who, along with Aldrovandus of Bologna, made a series of observations on the formation of the chick, day by day, in the incubated egg, which were described in a work published in 1573, and (2) Hieronymus Fabricius (ab Aquapendente), who, in his work De formato foetu, first published at Padua in 1600, gave an interesting account, illustrated by many fine engravings, of uterogestation and the foetus of a number of quadrupeds and other animals, and in a posthumous work entitled De formatione ovi et pulli, edited by J. Prevost and published at Padua in 1621, described and illustrated by engravings the daily changes of the egg in incubation. It is enough, however, to say that Fabricius was entirely ignorant of the earlier phenomena of development which occur in the first two or three days, and even of the source of the embryonic rudiments, which he conceived to spring, not from the yolk or true ovum, but from the chalazae or twisted, deepest part of the white. The cicatricula he looked upon as merely the vestige of the pedicle by which the yolk had previously been attached to the ovary.
  3. Along with the work of W. Hunter must be mentioned a large collection of unpublished observations by Dr James Douglas, which are preserved in the Hunterian Museum of Glasgow University.