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Gladstone RJ. and Wakeley C. The Pineal Organ. (1940) Bailliere, Tindall & Cox, London. PDF

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The Pineal Organ

Chapter 3 Types Of Vertebrate And Invertebrate Eyes

By the study of the adult organ and different stages of its development in the various types of eye — " upright " or " inverted," " simple " or " compound," " single " or " composite " — it has been shown that the receptive or sensory cells of all these types have been evolved by modification of the surface layer of epithelium. In invertebrates the epithelium is derived from the " hypoderm " which lies beneath the cuticle (Fig. 4).

Fig. 4. — Section through the Ocellus of a Young Dytiscus Larva. (After Grenacher.)

ct. : chitinous cuticle. rh. : rods.

vc. : cells of the vitreous body. re. : retinal cells.

/. : cuticular lens. n.o. : optic nerve. hy. : hypodermis.

In vertebrates the sensory epithelium originates from the medullary plate, or " neural ectoderm." This is at first spread out on the surface of the embryo and forms an elongated placode of thickened epithelium continuous at its edges with the surrounding cutaneous ectoderm, and in this respect it resembles the olfactory, otic, and branchial placodes (Fig. 5, p. n). A pit, the optic groove, then appears on each side in the situation of the future optic vesicle (Figs. 6, 7, 8). Later, when the medullary folds close in to form the neural tube, the optic pits appear as hollow evaginations springing from the sides of the neural tube. The

Fig. 5. — Transverse section of Open Neural Plate of Rana palustris, near its Anterior End, showing the Position of the Optic Rudiments. E.,

ALREADY MARKED OUT BY THE FORMATION OF PIGMENT.

CE. : Cutaneous epithelium. N.Pl. : Neural plate.

(After Eycleshymer, 1895, Textbook of Embryology, Vol. II, Graham Kerr.)

expanded outer end of each outgrowth is known as the primary optic vesicle, and the constricted neck is the optic stalk. The stalk is at first a hollow tube which connects the cavity of the primary optic vesicle with

Fig. 6. — Model of the Head of a Pig Embryo 47 mm. (16 days), showing the Optic Grooves on the Surface of the Open, Neural Plate. The Model is viewed from the Front and Left Side. (After Froriep.)

Op.Gr. : Optic grooves.

the third ventricle ; and its opening into the ventricle corresponds to the mouth of the original pit or groove which opened on the surface of the open medullary plate. The epithelium, which forms the outer part of the primary optic vesicle and later becomes invaginated to form the sensitive part of the retina, does not appear at this stage of development to differ markedly from that of the lens placode.

The invagination of the outer part of the primary optic vesicle into the ensheathing segment which becomes the pigment layer of the retina constitutes the essential structural difference between the " upright eye," typical of invertebrates, and the " inverted " eye which is characteristic

Fig. 7. — Dorsal View of the Head Region of a Human Embryo at an Early Stage of Development, showing the Optic Grooves before the Closure of the Neural Tube. (Legge embryo, 12 somites, after Bartelmez and Evans.)

Am. : Cut edge of Amnion.

Ch. : Site of the future optic chiasma, where the right and left halves

of the primordium of the optic crest become continuous anteriorly. M.B. : Midbrain. Op. Cr. : Stippled area representing the region beneath which the cells

of the optic crest originate. Op. S. : Optic groove. P.O. Cr. : Primordium opto-cristale. Rh. A. : Anterior segment of Rhombencephalon. 5. Cr. : Sulcus cristale. 5. Med. : Sulcus medullaris. S.18 : Arrows indicating the plane of section Fig. 8.

of the paired lateral eyes of all vertebrates. In the inverted eye the receptive end of the sensory retinal cells — rods and cones — is turned away from the source of light, entering the eye through the pupil. In those animals, however, such as the horse and ox, in which a tapetum lucidum is present on the retinal surface of the choroid coat and gives to this a metallic lustre, it is believed that light is reflected by it on to the outer

Fig. 8. — Section passing through the Optic Groove and Optic Crest in the Plane which is indicated by Arrows at S.i8 3 in the preceding Fig. 7.

am. : Amnion.

ar. ao. I. : arcus aortas I.

area V. : area of fifth cranial nerve.

atr. : atrium.

bulb. ao. : bulbus aortas.

cr. r.cur. : crista neuralis prosencephali.

end. c. : endothelial canal of bulbus aortas.

membr. br. I. : membrana branchialis I.

pericard : pericardial cavity.

ph. : pharyngeal cavity.

pr. op. cr. : primordium opto-cristale.

sac. vit. : vitelline sac.

sulc. op. : sulcus opticus.

ends of the rods and cones ; but whether a tapetal layer is present, or is absent as in the human eye, it is universally held that the rods and cones are the sensitive elements of the retina and that light reaches them by passing through the transparent anterior layers which intervene between them and the refractile elements — cornea, aqueous humour, lens, and vitreous. The relation of the nerve fibres to the sensory cells of the retina

Fig. 9. — Vertical Median Section through One of the Three Frontal Ocelli, or Stemmata, of a Blow-fly Imago. (After T. B. Lowne.)

c. : cuticle. hyp. : hypodermi.

c.l. : cuticular lens. n.f. : nerve fibres.

pg. : pigment cells forming fibrous sheath, continuous with the perineural sheath.

pr. sp. : preretinal space, r. : rods. ret. : retina.

v. : vitreous cells, continuous with hypoderm cells. These cells, which are present in the imago as a layer of tall, columnar cells, degenerate and in the mature animal exist only as a very thin stratum which is easily overlooked.

is well seen in Fig. 9, which represents an invertebrate eye of the upright type, and Fig. 10, A, B, the developing " inverted " lateral eye of a vertebrate.

The retina of both " upright " and " inverted " eyes may be either " simple " or " compound." The simple retina consists of a single layer of sensory cells, as in Fig. 9 ; the compound retina of two or more layers of sensory or neuro-sensory cells, as in the compound faceted or non-faceted

Fig. 10. A — Section through the optic vesicle of a human embryo, 7 mm., showing continuity of the cavity of the primary optic vesicle with the cavity of the third ventricle. The surface (SC.) of the invaginated layer of the optic cup was originally on the superficial aspect of the medullary plate. L. : lens vesicle.

B — Schematic diagram of a vertical section of the optic cup of the 7-mm. human embryo shown in A, representing the positions of the retinal layers when these are fully differential, in order to demonstrate the relation of the rod-and-cone layer of sensory cells to the cavity of the primary optic vesicle, the lining epithelium of which was originally on the superficial surface of the neuralplate, and later formed the epithelium at the bottom of the optic groove, before the closure of the medullary folds. The nerve-fibre layer of the retina corresponds to the deep surface of the neural plate. When the optic cup is formed it becomes directed towards the outer surface of the cup by the inversion of the ventro-lateral segment of the primary optic vesicle. The arrows indicate the direction of the decussating and tract fibres of the optic nerve in the region of the future chiasma.

hi. p. : bipolar cells.

c.p.op.v. : cavity of primary optic

vesicle. g.c. : ganglion cells. /. ; lens.

nf.l. : nerve-fibre layer.

p.l. : pigment layer of retina.

s.ep. : sensory layer (rods

cones). III. V. : third ventricle.

Fig 11. — Longitudinal Section through the Optic Stalk and Eye of a Crayfish (Astacus fluviatilis). (Original.)

showing a smooth non-faceted cornea, continuous with the cuticle of the stalk ; Sc. : Semper's cells partially concealed by pigment ; pc. : the conical pigment caps continuous with the pigment sheath surrounding the distal segments of the crystal rods cr. ; these are socketed in the cup-shaped outer ends of the inner segments of these cells ; ri ., n"., n. : three zones of retinal nuclei, the middle of which is obscured by pigment ; bm. : basement membrane which is continuous at the margin of the retina with the basement membrane beneath the hypoderm cells of the cuticle. The pedicle shows four enlargements or optic ganglia, containing nerve cells, nerve fibres, a reticulum of supporting fibres, the neuropil, rip. ; and spirally or transversely striated, refractile spindles, sp. ; m. : insertion of muscle fibres into the hypodermal membrane of the optic stalk ; o.sh. and i.sh., outer- and innerfibrous sheaths of the pedicle between which is a loose layer of mesenchymal tissue. There is a marked spiral twist of the central nervous axis of the pedicle, bv. : blood vessels ; nf. : nerve-fibres.

eyes of certain crustaceans and the retina of the paired lateral eyes of mammals (Figs. 11 and 12). Simple upright eyes are present in the lower and some of the higher invertebrates and are also found in the median paired eyes of both invertebrates and vertebrates (Figs. 9, 13, 14). They may occur in the form of simple patches of modified epithelium, pits, or hollow vesicles. From the inner ends of the epithelial cells elongated processes or nerve-fibres are given off. These leave the deep surface of the plaque or vesicle and join a subepithelial nerve-plexus or cerebral ganglion. The sensory epithelial cells are often pigmented in one part, the rest of

Fig. 12. — Diagram illustrating the Supposed Mode of Growth of Primary and Secondary Sensory Cells, and the Conversion of the Former into Bipolar or Unipolar Neuro-sensory Cells.

(Redrawn with some modifications from Arien-Kappers and Retzius.)

the cell being clear, or specialized pigment-cells may lie between or around the receptive cells. The outer end of a sensory or visual cell is frequently rod-like, and is termed the rhabdite. This part of the cell is clear and refractile, and it is believed to transmit the rays of light to the body of the cell in which the nucleus is situated and which is continuous at its inner end with a nerve fibre. In the more highly evolved types of upright eye, a circular fold of epithelium enclosing a layer of mesenchyme grows inward superficially and closing the mouth of an optic pit converts it into an optic vesicle (Figs. 33-35, Chap. 3, pp. 48, 49). When in this way the optic vesicle has been cut off, the epithelium lying over it and the under

Fig. 13. — Section through Eye of Acilius larva, showing the Natural Appearance with the Pigment in situ on the left, and the Retinal Cells as seen in a Specimen which has been bleached on the right. (After Gaskell.)

ct. : cuticle. p. : pigment.

gl. : cerebral ganglion. p.r.c. : pre-retinal cells.

hyp. : hypodermis. rh. : rods.

/. : lens. ret. c. : retinal cells.

n. : optic nerve. v. I. : vitreous layer.

Compare with Fig. 14.

Fig. 14. — Semidiagrammatic Section through the Right Pineal Eye, Pineal Nerve and Right Habenular Ganglion of Ammoccetes. (After Gaskell.)

Showing an optic vesicle of the simple upright type which resembles in some respects types found in certain of the invertebrates, e.g. Acilius (see Fig. 13). The outer or superficial segment of the vesicle consists chiefly of elongated clear cells which form an imperfect lens. The inner segment is the retinal layer, which on the right side of the diagram is represented as seen in a bleached specimen and on the left in the natural condition with the pigment in situ. It consists of elongated sensory cells, the distal segments of which are rodlike, while the proximal ends of the cells appear to be continuous with the component fibres of the main optic nerve, which ends in the right habenular ganglion. In addition to the sensory cells of the retina are certain oval and rounded cells which are peripheral in position and lie between the columnar cells of the retina and the capsule, and others

between the retina and the lenticular cells. The pigment appears to lie partly within the substance of the sensory cells and partly in specialized intermediate pigment cells between the sensory cells. Superficial to the optic vesicle are the connective tissue fibres of the cranial capsule, above this but not shown in the diagram is the parietal plug, which intervenes between the vesicle and the sub-epidermal stratum of connective tissue, the latter corresponds to the substantia propria of the cornea of the lateral eyes of vertebrates in general.

c.t. : connective tissue.

?i. sh. : nuclei of nerve sheath.

pig. : pigment.

pig. c. : pigment cells.

p.n. : pineal nerve.

ret. c. : sensory cells of retina.

r.h.g. : right habenular ganglion.

lying mesenchyme form a transparent layer termed the cornea ; or in some cases this layer is called " secondary cornea," whereas the unpigmented superficial segment of the optic vesicle is called the " primary cornea " (Fig. 36, Chap. 3, p. 50). When a simple upright eye has only a single lens it is classed as an " ocellus," a term also applied to eye spots and other simple types of eye. The lens of an invertebrate eye may be non-cellular or cellular. The non-cellular type is most frequently formed by a thickening of the cuticle or chitin, — cuticular lens ; sometimes as a condensation of the secretion of vitreous cells (Figs. 33-35, 38, Chap. 3, pp. 48, 49, 53). The vitreous may be formed from a secretion of the cells lining the optic vesicle, but in some cases it appears to originate from two or more very large cells in the cavity of the optic cup or vesicle, which degenerate and give rise to a clear viscous fluid, as in the eyes found on the back oiOnchidium (Fig. 39, Chap. 3, p. 54).

Fig. 15. — Longitudinal Vertical Section through the Parietal Eye of an Advanced Embryo of Anguis fragilis showing Distinct Boundary between Lens and Retina. (After J. Beard, Q.J. Micro. Sc, 29, 1889.) /. : lens. ret. : retina.

Cellular lenses may be formed in invertebrates by elongation of the hypoderm cells, as in the median eyes of the blow-fly (Fig. 9) or the ocelli of the larva of a beetle (Dytiscus) which shows a transition from the surrounding hypoderm cells through the elongated " vitreous " cells of the lens to the sensory cells of the retina. This type of lens is frequently combined with a cuticular lens which forms a transparent thickening of the cuticle over the centre of the " vitreous " part (Fig. 4, p. 10). A cellular lens formed from the distal wall of the optic vesicle is well seen in the median or " pineal eyes " of some lizards, e.g. in the blind-worm — Anguis fragilis and Sphenodon (Fig. 15 ; and Fig. 183, Chap. 20, p. 259). A good example of a cellular lens is also present in the remarkable eyes arranged round the edge of the mantle in the Scallop (Patten) (Fig. 107, Chap. 12, p. 149). Lastly, the " crystal cones " belonging to each component of the composite faceted eyes of certain Crustacea are partly " cellular," partly " vitreous," and will be described in the section dealing with the eyes of arthropods (Figs. 81, 95, Chap. 11, pp. 119, 133).

Single and Composite Eyes. — Groups of single eyes or ocelli, each with a separate lens, may be aggregated in a single organ which is best termed a composite faceted eye. These composite faceted eyes have to be distinguished from eyes having a compound retina, as in the lateral eyes of vertebrates, in which only one lens is present, but there are three layers of sensory cells : rod- and cone-cells, bipolar-cells, and ganglioncells. Unfortunately the term " compound " has been used by different writers to denote both the aggregate or composite faceted eyes and those in which the retina is made up of two or more layers of sensory cells. However, in many insects and Crustacea the two conditions are combined, the eye being both composite and compound. Thus the confusion in terminology is not so great as it might have been if they were separate.

The Relation of Ocelli to Composite Faceted Eyes. — A considerable amount of interest has been taken in the relation which the simple eye having a single lens has to the composite lateral eyes which are typical of many adult insects and Crustacea. The two types of eye may be present together in a single adult individual, or ocelli may occur in the larva which are replaced or supplemented by composite faceted eyes in the adult. The ocelli may be lateral or median or may be both lateral and median in position. They may occur singly or in groups (Fig. 16). Fusion of a pair of median eyes to form a single unpaired median eye is common, or in some instances where two pairs of median eyes are close together the members of one pair, usually the

anterior, will join, while the posterior pair of ocelli remain separate ; a group of three simple eyes thus arise from two pairs of such eyes, which originally were situated one behind the other, and between the lateral faceted eyes (Fig. 72, Chap. 11, p. no ; Fig. 249, Chap. 24, p. 361). The fused eyes frequently show regressive characters, being small and imperfectly developed as regards structure. Ocelli, moreover, are often present in the larval stage which disappear completely in the adult (Fig. 78, Chap, n, p. 117). An interesting departure from the general rule that the median eyes are simpler in type and less developed than the lateral eyes is found in the scorpion, in which the lateral eyes (Fig. 94, Chap, ii, p. 132) resemble the simple eyes or ocelli of insects (Fig. 9, p. 14) while the pair of larger median eyes differ from them in having the retinal cells arranged in groups, as in the composite eyes of certain insects and Crustacea ; they resemble the simple eyes, however, in having a nonfaceted single lens (Fig. 95, Chap. 11, p. 133). The whole question of the existence of the " median," " frontal," or " accessory " eyes in larval and adult insects and Crustacea, and the frequent disappearance of the larval eyes which takes place in the change to the adult form, is of the greatest importance in understanding the nature of the median or " pineal eyes " of vertebrates. We shall, therefore, attempt to give a brief sketch of some of the more essential points of these and of the lateral eyes in invertebrates, with the object of making a comparison between the two and showing the differences as well as the similarities in their structure and position.

Fig. 16. — Solitary and Aggregated Eyes of an Annelid — FLemopis sanguisuga. (After Ariens Kappers.)

Beside the median and lateral eyes of the head, eyes of different type appear in various parts of the body, e.g. on the margin of the umbrella in coelenterates, on the edge of the mantle in certain molluscs, and on the back in Chiton. The general form and connections also vary ; thus they may be stalked, sessile, or imbedded in a socket lined by a serous membrane. Some of the best examples of stalked eyes occur in the Crustacea, e.g. the crayfish and the shrimp ; among the Mollusca — snails and slugs ; and in vertebrates the " parietal-organ " or " pineal eye." In the lateral stalked eyes of the invertebrates, mobility is dependent on the movements of the stalk, which are carried out by muscle fibres within the stalk. The small pineal eye — " parietal organ " — of living vertebrates is usually immovably socketed in the parietal foramen, where it is surrounded by dense fibrous tissue. We have no direct evidence of its mobility in extinct animals ; the parietal foramen in many of the extinct reptiles and amphibia is, however, much larger than in any living species, and it is within the bounds of possibility that movements of the stalk or stalks similar to those which occur in the stalked eyes of invertebrates may have taken place.

In discussing these different types of eye it will be unnecessary to describe in detail certain varieties of eye, which although of considerable general interest, yet have no special bearing on the subject with which we are dealing. It is important, however, to note that a knowledge of the structure of certain atypical eyes, which owing to their position cannot be regarded as homologous with those of the head, although they have many points in common with these, is nevertheless of considerable value. The structural resemblances must have arisen in response to similar environmental factors and similar somatic conditions, e.g. the action of light on skin and pigment granules contained in the epithelium and subcutaneous tissue, and the existence of a structural basis for the transmission of impulses from sensory epithelial cells by afferent nerves to the central nervous system. The existence of such close structural resemblances in organs which are not truly homologous may serve the purpose of putting us on our guard against drawing conclusions which are seen to be unwarranted when all relevant circumstances are taken into account.

Good examples of such structures are the " luminous organs " seen on the ventro-lateral aspect of certain deep-sea teleosteans, e.g. Stomias boa (Fig. 17) and the " photospheria " on the thoracic and abdominal appendages of Nyctiphanes Norwegica, a crustacean closely allied to the cuttle-fishes. An interesting point in connection with these " photospheria," Fig. 18, ' is that in addition to the thoracic and abdominal luminous organs, a pair which are similar in structure to these have been shown by Vallentin and Cunningham to be present in the adult animal at the base of the stalk of each of the composite faceted eyes. Incidentally the appearance of this luminous organ in close association with the faceted eye suggests the possibility of the latter having been evolved as a modification of the more simple type of organ which is situated at the base of the stalk.

Fig. 17. — Stomias Boa — a Deep-sea Telostean Fish which is characterized by a Series of Luminous Organs arranged in Longitudinal Rows along the Ventro-lateral Aspects of the Body. (From Hickson, after Filhol.)

Claus, 2 in an earlier paper on Euphausia Mulleria, a nearly allied species, speaks of these organs as " accessory eyes " of which some are median and unpaired, while others are lateral and paired. He described them as ten small, globular, reddish organs, having a resemblance in many respects to such eyes as those of vertebrates and some molluscs and chaetopods. The pair of similar organs behind the two composite faceted eyes apparently escaped Claus's notice. Vallentin and Cunningham record that the light which is given off in " flashes " in response to stimulation is always intermittent in character, not continuous as in some " phosphorescent " organs, and they showed that the parts of the organ from which the light was emitted was the reflector (Fig. 18).

1 R. Vallentin and J. T. Cunningham, Q.J. Micro. Sc, 25, 319.

2 Claus, " Ueber einige Schizopoden und niedere Malacostraken, Messinas " (1863), Zeit.f. zviss. Zoo!., 13.

Fig. 18. — Section of the Photospherion of the first Abdominal Somite of Nyctiphanes Norwegica. (After Vallentin and Cunningham.)

co. : cornea. g- ganglion. ct. : cuticle.

/. : lens.

ep. : epidermis. lac. lacuna. f.m. fibrillar mass. p.c. posterior cellular layer. f.r.. fibrous ring. re. reflector.

Two possible ways of obtaining a composite eye from ocelli suggest themselves : (i) groups of separate ocelli may fuse to form a composite organ ; or (2) the individual cells composing an ocellus may divide in such a way as to form groups of cells lying side by side.

The latter process has been shown to occur by Kingsley 1 in the development of the stalked eyes of Crangon (shrimp), and this has been confirmed by other workers in different species of Crustacea and insects.

1 J. S. Kingsley (1886), Zool. Anz., 9, 597.

The compound faceted eye was found to develop from a single invaginated pit, a fact which proves that in these species the compound faceted eye is not to be regarded as derived from ocelli which have coalesced during ontogeny. Similar observations were made by Sedgwick, on Peripatus, and Locy, on spiders. The details of this development will be considered in the section on the eyes of crustaceans, and it will be only necessary to mention here that the fusion of ocelli to form a single median eye usually results in an eye of a simple type which shows regressive characters rather than progressive evolution ; and the ontogeny of an organ which is highly differentiated both in structure and function, such as the compound faceted eyes, results from the subdivision of the individual cells of a simple eye. This subdivision may take place (a) in a direction vertical to the surface, producing (1) undifferentiated or slightly modified epidermal or hypodermal cells, (2) retinal cells, and (3) ganglionic cells, continuous with the cerebral ganglia ; and (b) transversely to the plane of the surface epithelium, thus giving rise to groups of cells arranged round a single axial cell continuous with a single nerve fibre, the whole constituting an ommatidium ' or unit of the composite eye with its separate lens or corneal facet.

Fig. 19. A — Freshwater Planarian. Pigment spots are situated on the dorsal aspect of the head region, along the margin in front and laterally, and also two pairs one behind the other on the top of the head near the middle line.

B — Freshwater Planarian having a single pair of pigment spots on the dorsal aspect of the head.

C — A marine Turbellarian (Gimda) showing a single pair of pigment spots.

D — Transverse section through the eyes of Dendroccelum lac tea.

E — Section through one of the eyes of Dendrocozlum more highly magnified. (R. J. G.)

As previously mentioned, the fusion of two median eyes to form a single median eye is common in certain Insecta and Crustacea, and is frequently attended by regressive changes with diminution or loss of function ; and it will be useful at this stage of our description to consider the possible causes leading to (i) the approximation of a pair of eyes, and (2) their fusion and degeneration.

Fig. 20. Paired Lateral Eyes and Single Median Eye of a Gad Fly(Tabanus). (After Lang.)

ant. : antenna. mx. 1 : First pair of maxillae.

F. oc. : frontal ocellus. mx. 2 : proboscis which is formed

h. ph. : hypopharynx. from the labrum which encloses

Ibr. : labrum. the mandibles and maxillae.

L.E. : lateral or faceted eye. P.m. : palp o the first pair of

Mnd. : mandible. maxillae.

If we examine the simple, pigmented eyes of certain species of flat worm, e.g. the Planaria, we find that in some the eyes are arranged in a semicircle around the front and sides of the head, the eyes being on the dorsal aspect of the head and near its edge (Fig. 19) ; in other species in addition to the eyes round the margin of the head there is a pair, sometimes two pairs, of eyes placed medially and farther back than the others (Fig. 19, A) ; while in a third group the marginal row of eyes is absent and only the median pair is present (Fig. 19, B, C). These appearances are suggestive of the median paired eyes having originated from the marginal eyes, two of the central members of which, having become shifted backwards, are left behind the others on the dorsal aspect of the head, while the remaining marginal eyes are carried forward and laterally following the general growth of this region of the head. Whether paired eyes have arisen in this way or have been evolved independently, the foundation of a paired system of eyes is present in these simple Planarian worms. In higher types of invertebrates it is found that one such pair of eyes has become much more highly evolved and larger than the others, and constitutes the functional lateral pair of eyes, whereas the other pair or pairs remain small and simple in type. In some insects, e.g. the gad fly (Tabanus) (Fig. 20), the faceted lateral eyes having increased enormously in size and being directed forwards as well as laterally, have come so near together that the area which gives origin and nutriment to the median pair or pairs of eyes is encroached upon, and the whole area, including its vessels and nerves, being reduced, the median eyes also become reduced in size, approximated, and fused. It thus seems possible that a mechanical and nutritive as well as a functional preponderance of one pair of eyes over the other may come into play and contribute to the fusion and atrophy of the less developed pair. In other invertebrates, e.g. some of the lowtype crustaceans, more particularly Daphnia, Polyphemus, and Leptodora (Fig. 21), it is the lateral paired eyes which become fused. The underlying principle which is involved, however, is the same as in the fusion of the median eyes. There is, with the adoption of a parasitic life, a general reduction in the size of the animal and more particularly of the head, and with the loss of the necessity for using the eyes along with atrophy of the interocular tissues, the eyes are brought in contact with each other and fuse into a single organ.

1 Ommatidium : oppia, eye ; owjcctiov, diminutive of eye.

Fig. 21. — Three Specimens of Cladocera, belonging to the Sub-order Bran Chiopoda Of The Class Crustacea. The Lateral Eyes Are Sessile And Joined Together In The Median Plane To Form A Single Organ. The

Cladocera are greatly reduced in size (1 to 2 mm.) and Segmentation is VERY IMPERFECT.

A — Daphnia. B — Polyphemus. C — Leptodora.

The eyes of Daphnia and Polyphemus are, relative to the size of the body, very

large.

ant. 1 : antennule. d. gl. : digestive gland.

ant. 2 : antenna. /. : swimming feet.

br.p. : brood-pouch. ht. : heart.

E : eye. md. : mandible.

(A : after Claus. B and C : after Gerstaecker.)

Fig. 22. — Left Side of the Brain of Petromyzon, showing the Relations of the Pineal Organs and the Habenular Ganglia. (After Ahlborn.)

cbl. : cerebellum.

olf. I. : olfactory lobe.

c. hem. : cerebral hemisphere.

opt. I. : optic lobe.

ha. : anterior and posterior segments

po. : parietal organ.

of the left habenular ganglion.

pn. : pineal nerve.

ha. d. : right habenular ganglion.

pp. : parapineal organ.

inf. : infundibulum.

pt. : pineal tract.

int. br. : interbrain.

pt. b. : pituitary body.

nv. 1-12 : cranial nerves.

sp. n. 1 : first spinal nerve

The substitution of a single unpaired organ for the earlier paired median eyes is exemplified also in the pineal organ of the vertebrates.

The earlier pair of median eyes appear to have been supplanted by the more highly evolved lateral eyes, and thus undergo regressive changes. The vestigial median eyes are seen to arise in certain cases from a common stalk. This divides into two terminal swellings, which are often of unequal size. In some cases the smaller vesicle lies beneath the larger, as in Ammocoetes (Fig. 22) ; in other cases one organ, which is the less highly developed of the two, is shifted behind the other and the two vesicles in the adult animal lie approximately in the median plane, as in Sphenodon (Fig. 248, Chap. 24). These relations and their significance will be discussed in detail in the sections on the eyes of fishes and of reptiles (pp. 187, 242). The consideration of the geological evidence of the bilateral origin of the pineal organ in vertebrates and the fusion of the two parietal organs into a single median structure will also be postponed until later. It will be convenient, however, at this stage to describe the condition of cyclopia, which is produced by a process which is similar to that of the fusion of the median eyes of invertebrates and of the pineal organs in the vertebrates.

Cyclopia

The occurrence of one-eyed monsters has excited the curiosity not only of men belonging to our own period but also of the ancients. Among the latter Homer stands out pre-eminently, and his tale of the adventures of Ulysses and his fellow travellers with the giant Polyphemus has fascinated and stimulated the imagination of all students of mythology.

The questions which these ancient lays suggest, are :

Is there any foundation in fact for the classical myths of a race of giant cyclopes living apart from the world in insular seclusion?
Is it possible for human cyclopes to reach maturity and have normal vision ?

Both these questions may be answered in the negative. Among the records of mammalian cyclopean monsters we have not found any authentic cases of such having survived their birth by more than a few hours. Many cases of cyclopia are combined with a high degree of agnathia, in which the jaws are absent or imperfectly developed. In many of these cases the nasal cavities are completely shut off from the pharynx, and in some the pharynx ends blindly. 1 In the latter, the young would quickly die from suffocation, while in the former the infant would be prevented from breathing during the act of suction, and the process of sucking would have to be carried out by alternate respiratory and suction movements. In many cases, also, there are grave defects in the development of the brain, and the young are apt to die suddenly in convulsions soon after birth, as in cases of anencephaly. With regard to the possibility of a cyclops possessing normal vision, we find that in nearly all the published cases in which a dissection has been made of the median eye, the interior of the eyeball is almost completely filled with choroid and no mention is made of either retina or vitreous. Moreover, the lens has been found in some instances to be double, or if single it has usually shown signs of its composite nature. It is extremely improbable, therefore, that if it were possible for a human cyclops to reach maturity, he would possess normal vision.

1 R. J. Gladstone, " A Cyclops and Agnathic Lamb " (1910), Brit. Med. J., 2, 1159.

The cause of cyclopia and the frequently associated defect agnathia has been investigated by many authors and experimental embryologists, and numerous theories have been advanced in explanation of the defect. The more important of the earlier contributions were summarized by Schwalbe, who gives full references to the literature up to the year 1905. Since this period the various theories with regard to the nature of cyclopia and of the malformations which are usually associated with it have been profoundly modified by the conception of the regulation of growth by the action of an organizer — more particularly at centres of cell-proliferation such as the " apical bud " of a growing stem or the " dorsal lip " of the blastopore. Some of the more recent publications on the nature of cyclopia are referred to in a paper which was published by us jointly in the Journal of Anatomy (1920) on a " Cyclops Lamb (Cyclops rhinocephalus)." In this communication we pointed out that a distinction may be drawn between those cases of cyclopia which occur in primarily double-headed monsters as the result of the fusion of the outer segments of eyes derived from two heads, and those which occur in single-headed monsters, the cyclops eye being due in these cases to the fusion of the temporal halves of the eyes belonging to one head in which the central region of the head, including the nasal halves of the two eyes, has failed to develop. As a type of the former we may select an example of the well-known class Cephalothoracopagus monosymmetros, in which the two heads are united in such a way that two " secondary faces " are formed (Fig. 23, A and B). One of these faces may be regarded as looking forwards and the other backwards. The secondary face in A is apparently complete, whereas the secondary face on the opposite side of the double-head seen in B is incomplete, there being neither nose nor mouth, and there being but one palpebral aperture, p.ap., in the situation of a cyclops eye which is hidden from view by the fusion of the outer segments of upper and lower eyelids belonging to the two heads. The difference in the two heads is accounted for by the obliquity of the primary median antero-posterior axis of the two heads. If these had been in the same plane and at right angles to the primary dorso-ventral median planes of the two conjoined embryos, each secondary face would have been complete and similar, as in the Janusheaded monster shown in Fig. 24, A and B. In this example each " secondary face " has two eyes, one of which belongs to the foetus designated Y, the other to the twin foetus Z.

Fig. 23. — Cephalo-thoracopagus Monosymmetros (Duplicitas Posterior). (Redrawn from Schwalbe.)

A and B, the same specimen viewed from opposite sides. The letters Y and Z denote the individual components of the twin monster, and the letters / and r the left or right side. A, complete "secondary" face, Y r Z 1 ; B, incomplete " secondary " face Z r Y 1 showing a single palpebral aperture and fused eyelids covering a cyclops eye. The nose and mouth are absent and the ears approximated.

Fig. 24. — A Janus-headed Monster, Cephalo-thoracopagus Disymmetros (Duplicitas Posterior). (Redrawn from Schwalbe.)

The two " secondary " faces Y T +Z l and Z r - Y l are almost identical, and look in a direction which is away from and at right angles to the median dorsoventral planes of the two foetuses. In the disymmetrical type of Cephalo-thoracopagus these planes coincide.

Another type of double-headed monster — Duplicitas anterior (Diprosopus) — in which cyclopia sometimes occurs is shown in Fig. 25. In this form the two faces look forward in the same direction and the cyclops eye

Fig. 25. — Diprosopus. Duplicitas anterior.

Median eye formed by the union of the nasal half of the left eye of the right foetus, with the nasal half of the right eye of the left foetus.

(After Sbmmering, from Die Morphologie der Missbildungen : Schwalbe.)

is bounded by the inner or nasal segments of four eyelids (two upper fused together, and two lower). The eye itself is formed by the growth in contact with each other of the inner or nasal halves of the opposed organs, the temporal halves being suppressed. The auricles of the external ears on the opposed sides are also suppressed, but a small opening below the palpebral aperture and at the same level as the mouths represents the common external auditory meatus. An X-ray photograph showed two vertebral columns extending as far as the single pelvis, where fusion took place in the sacral region. There was complete absence of the arms and legs on the opposed sides. Notwithstanding the marked difference in general form between the Cephalo-thoracopagus and the Diprosopus types, the principles which are concerned in the development of the cy clops eye belong to the same category, although in the one case (Fig. 23, B)

Fig. 26. A — The dorsal halves Y and Z of two Triton gastrulas grafted together so that the directions of invagination at their blastopores are directly opposed to each other.

B — The resulting embryo showing crossed doubling — duplicitas cruciata — each half gastrula has developed a single posterior trunk region with spinal cord and two "secondary" head regions. These are formed at right angles to the longitudinal axis of the trunks.

L R, region which will give rise to the \ ^ L and R eyes of one "secondary" face; (R+L) region which will give rise to the cyclops eye of the other secondary face.

Fig. 27. C 1 — A later stage of the duplicitas cruciata larva, viewed from the direction of the arrows L R seen above the drawing in B, Fig. 26. In C- the same larva is viewed from the direction of the single arrow (R-tL) in B, Fig. 26, which points to the region which will give rise to the cyclops eye, seen in C 2 . In both C and C 2 the trunk and tail regions are viewed from the side. The two " secondary faces " are developed so that each is directed at a right angle away from the dorso-ventral plane of the bodies of the larvae.

Z : the component larvae, dorsal. V : ventral.

(After Spemann.)

the cyclops eye is formed by the union of the temporal halves of the opposed eyes and in the other (Fig. 25), by the union of the nasal halves of the two opposed eyes. In both instances the segments of the developing eyes which have grown in contact with each other have been suppressed, or, more correctly, have failed to develop. In Cephalo-thoracopagus monosymmetros it is the inner parts of the developing facial regions which first come into contact with each other on the cyclopic side, and these consequently fail to develop, whereas the outer parts of the face, being deflected, remain free, and thus undergo development ; this will be explained later when dealing with the regulation of growth by the influence of an organizer, namely the dorsal lip of the blastopore, as when the normal course of development is interfered with by growth contact, in the experimental grafting of two gastrula-halves together and the formation of a Duplicitas cruciata, as described by Spemann (Figs. 26 and 27).

In the second type of cyclops, namely that occurring in single-headed monsters (Figs. 28, 29, and 30), the cyclops eye is formed by the more or less complete fusion of the outer or temporal segments of the right and left eyes of a single individual. It is accompanied by absence or defective growth of the median parts of the head, including the inner or nasal segments of the eyes and eyelids, the nose and mouth, the frontal region of the cranial part of the skull, and the corresponding parts of the brain. It is common in domestic animals — cats, dogs, sheep (Fig. 28), and cattle (Fig. 28 A, b) — and frequently occurs in artificially reared fish, amphibian and reptilian larvae, and also in artificially incubated eggs. The injurious agents which have been employed in the experimental rearing or the artificial incubation that have resulted in the formation of these anomalies are : (1) mechanical injuries, e.g. separation of the blastomeres, incision, excision, and destruction of growing parts ; (2) the addition of magnesium, lithium, and other salts to the water in which the larvae are reared ; (3) raising or lowering the temperature above or below the normal ; (4) variations in the amount of oxygen or carbon dioxide ; (5) narcotics and poisonous drugs such as chloroform, chloretone, and potassium cyanide. The results obtained by such treatment vary not only with the degree of the injury inflicted and the part injured, but also with the particular stage of development reached at the time when the experiment is made. Thus the production of normal or of cyclops eyes in Triton or Ambly stoma larvae appears to depend on the presence or absence of the anterior part of the entodermal gut-roof, which acts as a regulator or organizer on the presumptive eye-region in the neurula stage of development. If the anterior and central region of the entodermal gut-roof is injured there is a liability to cyclops formation, owing to interference with the normal organization of the optic vesicles and cerebral hemispheres from the overlying neural ectoderm. If the whole eye-region is destroyed, anophthalmia will result.

One of the most important deductions to be made from these experiments is, that since they have been carried out on fertilized embryonic material which was primarily normal, the anomalies have been produced

Fig. 28. — A Cyclops Lamb (C. RhinoCEPHALUS) VIEWED FROM IN FRONT.

The tubular projection which springs from the frontal region is the " proboscis " ; the single nasal orifice showed traces of its bilateral origin by fusion of the right and left nostrils. In the centre of the face is the single palpebral aperture, and the median eye, which was formed by the fusion of the outer parts of the right and left eyes. There were two corneae and two lenses, but a single optic nerve. All the median structures, the septum of the nose, the internal orbital muscles and their nerves, were absent.

Fig. 28A, b— Head of Cyclops Calf.

A — View from the front.

B — Seen from the side.

(An artificial glass eye has been inserted into the eye-socket of the cyclops.)

by environmental factors ; and so far as the experimental material is concerned are not due to germinal variations — in other words, the defects have not been inherited and are not due to defects in either of the two germinal cells. Moreover, it seems probable that the occurrence of identical defects in mammals and in the human subject may also be attributed to injury or faulty nutrition affecting the embryo in the very early stages of development, although obviously it does not exclude the possibility of a defective condition of either of the germinal cells being the cause of a defect in the subsequent growth of the embryo.

Fig. 29. — Various Degrees of Regeneration and Head Differentiation after Amputation of the Head Region in Planaria. (After Child.)

A — normal ; B — partial fusion of eyes ; C — cyclops eye, lateral sensory projections approximated and directed forwards ; D — cyclops eye, lateral sensory projections fused ; E — anophthalmos, head reduced in size.

The experiments carried out by Child on Planaria (Fig. 29) and by Stockard on Fundulus (Fig. 30), both indicate that the use of depressant agents produces what is known as " differential inhibition " on growth processes. Thus the most actively growing parts at particular periods of development are the most susceptible to the influence of the drug and suffer most. One of these areas, namely, the interocular and adjoining regions, may be specially mentioned as being a zone where active proliferation and differentiation is taking place, and as being more affected or susceptible to injury than the rest of the head, both in the regenerating head after amputation of the head region in Planaria and in the intact ova of developing Funduli during the gastrular stage of development.

Incidentally it may be mentioned here, with reference to the discussion which follows on the nature of double-monsters, that two-headed Planaria may be produced experimentally by splitting the anterior end of an early larva and preventing the two halves from uniting. Each head will show bilateral symmetry and develop the normal pair of eyes and sensory organs.

Thus two organizing centres may be obtained after the stage when a single normal organizer has already been established. Further, it is well known that twin or even multiple gastrulae may occur in normal ova : as for example, in the Texas armadillo, which has four primitive streaks, and a South America species of armadillo, which has eight, and normally eight offspring at a single birth. These are believed to arise by the subdivision of a single blastoderm, and to be comparable with the artificial dichotomy of a growing bud and possibly also the induction of twinning in lower animals by merely separating the primary blastomeres ; or the production of separate embryonic axes in the eggs of fishes by lowering the temperature or reducing the oxygen supply during the early stages of segmentation.

Fig. 30. — Larva of Fundulus Heteroclitus.

A — Normal larva with anteriorly placed mouth.

B — Incomplete cyclopean larva ; the two eyes are joined, and occupy the position

usually taken by the mouth. C — Complete cyclopean larva, with antero-median eye. Dorsal aspect.

M : mouth.

(After Stockard, from Dendy's Outlines of Evolutionary Biology.)

There is, in fact, abundant proof of the uniovular origin of true twins. Further, the occurrence of multiple births arising from a single ovum, as in the case of the two species of armadillo, is well known to be an inherited condition. Moreover, that multiple growth-centres, twin and single monsters may occur as the result of alterations in the environmental conditions has been irrefutably demonstrated by experimental methods in the lower types of animals, and their occurrence appears to be extremely probable as a result of injury, disease, or toxic conditions of the blood circulating in the placenta in mammalia.

These conclusions, as we shall see hereafter, have a very definite bearing on the development and inheritance of the single median-eyes of both invertebrates and vertebrates, and their study with special reference to cyclopia is, therefore, not irrelevant to the general purpose of this book. Both types of cylopia, namely, that occurring in double-headed monsters and that arising from a defective growth of the interocular region in single monsters, are brought about by the growth in contact with each other of apposed parts of two eyes, while the development of the remaining parts of the eyes which are situated in the interval between them is suppressed. The principle which is involved is the same whether the cyclops eye is developed from the outer or temporal segments of two eyes growing in apposition with each other, as in one of the two secondary faces of a Janus-headed monster, or whether the cyclops eye is formed from the inner or nasal segments of two apposed eyes, as in the double-faced (Diprosopus) monster, in which the two faces look in the same direction and all eyes are to the front ; moreover, it is evident that, whatever other causes may be at work, this same principle, of the suppression of the growth of the intervening parts, is concerned in the development of a cyclops eye in single monsters.

The following questions arise in connection with the causes of the suppression or arrest of development ; namely, is it due to :

A lack of building material from which to form the missing parts ?
A lack of or defect in the organizing power of a growth centre ?
A displacement or arrest of development due to the growth of two parts in apposition with each other ? Finally, is the arrest to be considered as due to a combination of any two or all of these three factors ?

Before attempting to answer these propositions we will pass on to the general question of the production of double-monsters and give a brief historical sketch of the earlier conceptions of the problems which are involved, one of which held that a double monster was the resu't of a splitting of the early embryonic rudiment, either at the head-end — " anterior dichotomy " — or at the tail-end — " posterior dichotomy " ; the other that two embryonic rudiments appeared in a single embryonic area and that these rudiments afterwards came into contact and grew together, the corresponding parts uniting with each other so as to form a " duplicitas anterior " or a " duplicitas posterior."

Each of these two hypotheses has assisted in the proper comprehension of the various conditions which are presented in the whole series of anomalies involving duplication of parts, and both are necessary, although in a modified form, in order to appreciate fully the way in which according to the newer conceptions an organizer has the power at an early stage of development to determine from the outset the mode of development of a particular part ; or at a later stage, of overriding the previously determined power of a particular part of the embryonic area to form a particular region or organ, such as that of the eyes, nose, and mouth. The older observations and records of blastoderms showing two separate embryonic axes and the explanations which were put forward to account for these were of great value in solving some of the general problems arising from the occurrence of twin or multiple births and double monsters, and they have in many instances formed the basis on which the more recent work of Spemann and others has been founded. The new conceptions, therefore, must be regarded as supplementary to rather than as replacing the older conceptions. The latter cleared the way for the newer work by establishing the distinction between uniovular and biovular twins ; the origin of double monsters from a single ovum, in which two gastrular invaginations and embryonic axes were present ; many of the details with regard to gastrular invagination and the formation of the primitive streak and head-process, and other important points, relating to relative rate of growth of particular parts, and also dominance of one part over another.

Beginning with what is known as the " radiation theory " of Rauber, Fig. 31, A, B, C, represents in a schematic manner three stages in the development of a Duplicitas anterior in the blastoderm of a bony fish. Rauber considered that the occurrence of double monsters was due to the formation of two embryonic buds at the thickened margin of the embryonic disc in place of one. These buds grew towards the centre of the disc in a radial direction. In those cases in which the embryonic axes were exactly opposite to each other the germinal disc would be divided by a vertical plane passing through the longitudinal axis of each embryonic bud, comprising an area including 180 of the whole. If, however, the embryonic buds arose close to each other, as represented in Fig. 31, A, the part of the germinal ridge mn between them, which he termed the " inner intermediate zone," would be much shorter than the rest of the circumference, ystz, which he called the " outer intermediate zone " ; in the formation of the head-regions of the double-monster, the segments mn and yz of the germinal ridge will be added to the original ingrowing embryonic buds as represented in Fig. 31, B ; whereas when the whole of the inner intermediate zone mn had been utilized, the remaining segments of the ridge st would come in contact and give rise to the single body and tail, by fusing with each other in the median dorso-ventral plane, as appears in C, in which a complete Duplicitas anterior is represented. In this and the preceding drawing it will be seen that when all the available inner intermediate zone has been utilized in the formation of the anterior end of the embryo, the remaining parts of the outer zone. st will come into apposition and fuse so as to form the right and left halves of the single body and tail.

Fig. 31. A 3 B, C — Scheme indicating the mode of formation of Duplicitas anterior according to Rauber's theory. ab : vertical or antero-posterior diameter dividing the germinal disc or blastoderm into right and left halves and corresponding to the principal, or dorsoventral, longitudinal axis of the body of the future larva ; hh : head-ends of the embryonic " outgrowths " ; mn : the right and left halves of the inner intermediate segment. These, with the corresponding parts of the embryonic outgrowths, will give rise to the internal or opposed halves of the two head-regions of the double monster ; yz : the corresponding outer segments of the margin of the germinal disc ; these will form the external (left and right) halves of the twin head and neck regions ; st : the remaining parts of the germinal ring, which by uniting directly with each other will form the right and left halves of the single body and tail of the abnormal embryo.

D, E, F — Figures illustrating the formation of Duplicitas anterior in the salmon's egg from two gastrular invaginations, after Hertwig, in accordance with the " concrescence theory " of His. This conception differs from Rauber's in that Hertwig considered that the multiple formations are due to multiple gastrular invaginations at the margin of a single germinal disc, whereas Rauber considered the whole germinal ring as being the boundary of the gastrula-mouth or blastopore. Z : intermediate segment between the two gastrular invaginations ; k\ k- : right and left head rudiments of a double monster; itzv 1 , -, 3 : interrupted lines indicating the expansion of the germinal disc.

A modification of Rauber's theory was later described by Hertwig, who pointed out that Rauber was wrong in considering the whole extent of the germinal ring as constituting the boundary of the blastopore, and that multiple neurulae developed from a single gastrula. Hertwig, on the contrary, believed that multiple growths develop from several gastrular invaginations, in confirmation of which standpoint he cited the discovery of double gastrula? in Amphioxus by Wilson and the observations of Schmidt, who demonstrated the existence of two separate gastrular invaginations in the germinal discs of young trout ova. In explanation of his theory he suggested the modification of Rauber's theory which is illustrated in Fig. 31, D, E, F. In D he shows two gastrular invaginations, k 2 , k l close together and growing inward from the margin of the germinal disc. Between them is a short " inner intermediate zone " as described by Rauber, and the rest of the circumference corresponds to Rauber's " outer intermediate zone." In E it is seen how, as the disc enlarges, the adjoining parts of the ring are gradually transformed into the " primitive mouth " (or, in other words, become included in the boundaries of the two blastoporic openings which now open by a single common orifice). It is obvious that the nearer the embryonic rudiments or axes are to each other, the sooner will the inner intermediate zone be used up in the formation of the embryo, and the right and left halves of the outer intermediate zone come into contact ; and that as a result the two primarily separate gastrular cavities will form posteriorly a single common gastrular cavity, as shown in E and F. In the further course of development the margins of the blastopore or primitive streak can only be increased by additions from the lateral intermediate zones, which meet one another in the median plane, as in the formation of a normal single embryonic axis. Hertwig further emphasized the important point that multiple formations probably arise at the time of gastrula-formation, or even before the time when a gastrula is actually present.

Fischel also criticized Rauber's " radiation theory " ; he recognized that a generalization of this theory was in many instances met by grave difficulties, and further that it was even insufficient to explain the development of a Duplicitas anterior, for which Rauber had first postulated the theory as affording a solution. Making use of the schematic diagrams, Fig. 32, A, B, C, which were employed by Kopsch to illustrate the development of Duplicitas anterior according to the " concrescence theory " of His (see legend), Fischel and Kopsch point out that only a very small part of the cellular material of the germinal ring is utilized in the formation of the head-region, and that the greater part of the ring contains the material for the lateral and ventral parts of the body of the embryo. During the expansion of the germinal disc there occurs in the first place a drawing together of the head-forming regions from which, by union in the median axis of the embryo, the right and left halves of the head are produced. The projecting embryonic bud contains the canalis neurentericus in the region of Hensen's node, and later there is formed, by a backward growth from this point, the body and tail of the embryo, during which the remaining section of the germinal ring surrounds the yolk and contributes the lateral and ventral parts of the embryo. As a result of his observations on the development of a series of double-monsters, Fischel emphasizes the limitation of the zone which will give rise to the embryonic rudiment to a relatively small region of the germinal ring, and also the downward (ventral) direction of this growth. He admitted, however, that fusion played an important role in the production of many forms of duplicity.

Fig. 32. — Schematic Drawings illustrating the Formation of a Doubleheaded Monster, Duplicitas anterior, on the Basis of the Concrescence Theory. (After Kopsch.)

A — Germinal disc with two embryonic rudiments at the " lozenge-shaped stage of development and situated close together. The inner intermediate segment is indicated by Roman figures ; the outer segment by Arabic figures. k' 1 , k 1 : head-ends of the embryonic rudiments.

In B the whole of the intermediate segment has been utilized in the formation of the opposed sides of the twin head-ends of the Duplicitas anterior.

In C the " inner " intermediate zone, no longer being available for the formation of the embryo, the outer segments of the growing margin of the germinal disc meet and fuse to form the single body and tail-end, as in normal development.

If the two embryonic rudiments were situated directly opposite each other, it is assumed that two completely separate uniovular twins would be formed — the so-called " inner " and " outer " intermediate segments being equal in extent and sufficient to form two whole embrvos.

Marchand, with whom Dareste may be included, may also be regarded as a supporter of the fusion theory. He held that by far the greater number of symmetrical double-monsters were formed by an extensive union of originally separate embryonic rudiments on a germinal vesicle, although in cases of incomplete anterior doubling he accepted an origin by means of bifurcation. The incomplete Duplicitas posterior he thought most probably arose from two originally separate rudiments (primitive streaks). Schwalbe dissents from Marchand's view and more particularly with reference to the bifurcation theory in connection with the posterior variety. He further points out a group of cases which has to be considered, and which can neither be regarded as belonging to the category of fusion nor in the strict sense of the word to the cleavage theory, and which he refers to under the designation " theory of incomplete separation." Now Ahlfeld defined the controversy between the cleavage and the fusion theories in the following words : " the one assumes that at first a common rudiment was present which in the course of development divided ; while the supporters of the other theory believed that from the very first two separate rudiments can be observed on the germinal vesicle, which in the course of development become united." The theory of incomplete separation coincides with neither of these two theories exactly, and Kaestner contended that the theory of incomplete separation was in reality a modified cleavage theory dressed up in new clothes, and asserted that incomplete double-monsters were not in any particular case one part simple, one part doubled, but were one part completely doubled, the other incompletely doubled ; also that in his opinion those cases in which, instead of there being one primitive streak, two primitive streaks are present, the whole germinal disc to the most distant parts of the embryonal region, into which neither the primitive streak nor the head process has yet penetrated, is already determined or adapted for the development of two embryonal rudiments. Also that all cases of double-monsters which hitherto have been completely examined, proved to be in reality double in all parts ; and where in a general view organs appeared to be simple, these showed on section more or less distinct traces of duplicity.

This statement is, however, challenged by Schwalbe, who gives as an example to the contrary cases of slight Duplicitas anterior (Diprosopus) in which some parts are not incompletely doubled. It may be noted, however, that in the case of Duplicitas anterior (Diprosopus) shown in Fig. 25, although the body on superficial inspection appears to be single, an X-ray photograph showed two vertebral columns extending as far as the pelvis. According to Kaestner's view, this case would represent incomplete doubling.

Kaestner states that if two primitive streaks are present, the axes of two medullary grooves will also be laid down and the position of two foregut grooves determined. If the two primitive grooves are not sufficiently separated from each other to allow of all the organs of the two embryonic rudiments to be infolded, an arrest of development occurs which may be compared with the interference of two wave-systems and the changed conditions of wave-form occasioned by this. Thus if two primitive streaks are sufficiently far apart, two complete medullary grooves will be formed, with a notochord situated below the floor of each groove. If the primitive streaks are very close together there will be one double medullary groove which is wider than normal, and shows two subsidiary grooves lying parallel with each other in its floor. The subsidiary grooves indicate its composite double character, and beneath each of these is a notochord. When the medullary folds which flank the main double medullary groove unite, a single neural tube will be enclosed. This is, however, not a simple tube, but is compound in nature. At the extreme anterior end a double bud is present which has the power to form two separate forebrains. If the embryonic axes are still more closely approximated, a single forebrain will be formed, although developed from two embryonic axes. Kaestner states that many authors would describe the latter condition as due to the fusion of two medullary tubes, but " no — they are, on the contrary, incompletely separated."

Rabaud puts a slightly different interpretation on this process, namely that in dual or twin developments we have a differentiation within a common region of two developmental centres.

This view is very similar to the modern conception of two organizers dominating a region which has not yet been completely determined, and which would under normal circumstances give rise to a different structure. Where the spread of the two centres is interfered with by mutual contact, as in Fig. 26, B, further growth in that direction is arrested or proceeds in a different direction. If the primary dorso- ventral planes of the two embryonic axes are in the same plane, the resulting double-monster will be symmetrically developed ; but if the primary dorso-ventral planes of the two embryonic axes are disposed in different planes, so that when the two axes meet the primary dorso-ventral planes form an angle with each other, the resulting secondary surfaces will be unequal, as in Fig. 23, A and B, and there will be a tendency towards the suppression of the central parts on one side, with the production of such deformities as cyclops and synotia. Asymmetry or inequality may also arise from a difference in the size or vitality of the two growth-centres. Finally, as is suggested by experimental interference with the development of normal ova, the blastomeres or the organizing centre may be divided into two or more growth-centres by constriction or other means and the developmental rudiment of a double organism initiated. Moreover, as previously conjectured, it seems likely that alterations in the physico-chemical environment of the ovum in the gastrular or pre-gastrular stages due to injury or disease may produce similar defects under natural or non-experimental conditions in both non-placental and placental animals.

The next question which it is necessary to consider is, Can the causes of these general defects be limited in their action to the development of particular organs ? And more particularly with reference to our present thesis ; Can primarily paired organs such as the nose, eyes, or ears lose their function, atrophy, and either become fused into a single organ or disappear altogether ? These questions involve another, namely, the inheritance of general and localized defects, such as albinism and haemophilia on the one hand and the inability to complete the development of particular organs on the other hand. As examples of the latter, we may mention the rudimentary teeth which have been found in the jaws of foetal whales and in the curious duck-billed Platypus (Ornithorhynchus) ; or, again, the vestigial limbs found in certain snakes, the vestigial wingbones of the kiwi, the New Zealand Apteryx ; or Stiedas organ in Rana temporaria (Figs. 162, 163, and 167, Chap. 19, pp. 228, 229, 233), and the median eyes of many invertebrates.

Associated with these questions is also that of change of function. Of this we have fewer examples than is generally supposed, for although a forelimb may be modified for use as a paddle, a leg, or a wing, its use as an organ of locomotion has not been altered ; perhaps one of the bestknown instances of change of function is the conversion of the swimbladder of fishes, a hydrostatic organ, into the air-breathing lungs of terrestrial animals. Now it sometimes happens that it is easier to build an entirely new structure than to improve and adapt an old one ; the latter is either destroyed in order to make room for the new building or is allowed to fall into decay. The latter alternative seems to have happened in the replacement of one organ by another in the course of evolution which sometimes happens in the animal kingdom, e.g. in the replacement of the median eyes of invertebrates by the lateral eyes, but as we shall see later, both median and lateral eyes seem to have been evolved from the simple ocellus. In other cases a particular organ having lost its original function is gradually moulded or transformed so as to fulfil a different purpose. In the case of the pineal organ, or epiphysis, of birds and mammals, opinion is still divided upon the question as to whether this structure is being transformed into a secretory gland or is being left as a derelict vestige, which is gradually disappearing or has already disappeared, as seems to be the case in crocodiles.

That causes of general defects of development may be limited in their action to the development of particular organs is a proposition that may be answered in the affirmative both with respect to ontogenetic and phylogenetic development. Thus if diminution or loss of function of an organ be taken as an example, it is obvious that the full development of an organ such as a muscle or sense-organ will be curtailed by want of function during the life of an individual, and it may also be inferred that the poorly developed muscles of domestic animals living in confined spaces, such as rabbit-hutches, as compared with those of wild animals, are defects of development which are inherited, because the stimulus — exercise or light — which brings about the full development of the organ has been absent in many successive generations.

Also, as we shall see later, primarily paired organs such as the olfactory or visual, if their function is curtailed or actually ceases, may in the course of phylogeny be reduced in size, displaced, fused into a single organ, and finally disappear. As examples of this we need only mention : (1) the fusion which has taken place of the paired olfactory organs in the class Monorhina, which includes among its living representatives the degenerate hag-fishes and the lampreys ; and (2) the formation of a single median eye by the fusion of paired vestiges of median eyes whose function has been usurped by the gradual evolution of highly differentiated lateral eyes, as has occurred in many of the arthropoda.

The inheritance of a grave defect such as cyclopia which is commonly associated with other defects, such as absence of the mouth and nasal passages and defective growth of the brain, is obviously excluded, as the individual is not viable ; moreover, the cause of the defect, as we have seen, is in many cases due to injury, defective nutrition, poisons, or other environmental conditions acting in a deleterious manner on the already fertilized ovum and more particularly during the gastrular and neurular stages of its development.

Development of the Lens and other Refractile Elements of the Eye

These may be derived from :

The cutaneous ectoderm or epidermis, including the cuticle and the hypoderm cells (Figs. 4, 9, and 10).
The superficial epithelial stratum of the retina, by a special modification of certain cells or parts of cells belonging to the retinal segment of the optic cup or optic vesicle (Figs. 33, 36).
The distal or superficial wall of the optic vesicle — hypoderm cells in invertebrates or neural ectoderm in vertebrates (Figs. 37, 10).
A condition intermediate between 1 and 3 in which the elongated hypoderm cells on the sides of the optic cup form a tube of clear refractile cells, having a very narrow lumen in front of the retina. These cells are continuous superficially with the hypoderm cells lying beneath the cuticle and proximally with the retinal cells (Fig. 38).
Mesodermal elements which become included in the dioptric apparatus of the more complex eyes. For instance, the substantia propria
A semi-fluid or gelatinous secretion from cells derived from :
1. The hypoderm cells or cutaneous ectoderm.
2. The retinal epithelium.
3. The mesenchyme.

Fig. 33. — Simple Optic Pit of a Limpet (Patella).

The pit is lined by pigmented epithelium, which is continuous at the margin of the pit with the cuticular epithelium. The outer ends of the cells are clear and rod-like. The nuclei are deep to the pigment layer, and the inner ends of the cells are continued into the fibres of the optic nerve, op. n. : optic nerve ; r. : retina.

(Cambridge Natural History, after Helger.)

Fig. 34. — Open Optic Vesicle of Trochus.

The cavity of the vesicle is filled with a semi-fluid secretion, the vitreous humour, v.h. ; op. n., optic nerve ; pig., pigment.

Fig. 35. — Closed Optic Vesicle of Murex, completely separated from the Surface Epithelium by a Layer of Mesenchyme.

A spherical non-cellular lens of the vitreous type is separated by a space from the sensory cells of the retina.

c.ep. : corneal epithelium. pig. : pigment.

cut. : cuticle. sc. : sensory cells of retina.

/. : lens. rh. : layer of rods formed of parts

mes. : mesenchyme. of the retinal cells.

op. n. : optic nerve.

The clear cylindrical cells lining the vesicle after having secreted the vitreous become differentiated in their inner parts as refractile rods, while their outer parts function as receptive sensory cells.

of the cornea in the lateral eyes of vertebrates, or in the form of a supporting tissue in the vitreous humour, or accessory structures such as the elastic lamina; of Bowman and Descemet and the capsule of the lens.

Fig 6 -Diagrams representing the Development of the Eyes in Decapoda and octopoda.

[Continued at foot of next page.

The refractile fluid or substance may be first formed in the substance of the cells, appearing as droplets in the cytoplasm ; thereafter it may be retained in the substance of the cells, either in a semi-fluid condition or a more solid state, as in the clear refractile rods or " rhabdites," or the " crystal cones " of some types of simple or compound eyes ; or it may be discharged as a secretion into the vitreous cavity. In some cases the whole cell degenerates, the cell boundaries and nuclei disappear completely, and adjacent cells coalesce to form a viscous mass which afterwards consolidates and assumes a lens-like form. In other cases two or more cells may become enormously enlarged so that they fill the greater part of the optic vesicle ; these become clear and highly refractile and may then function as a lens or vitreous humour (Fig. 39). Considerable importance has been attributed to the distinction between lenses which are cellular and lenses which are non-cellular ; and also to the type of epithelium which enters into their composition. The distinction is of importance more especially with reference to the type of lens found in the lateral eyes of vertebiates, which is cellular and epidermal in origin, and the lens of the " pineal eye," which is also cellular but originates from the distal wall of the optic vesicle, and is therefore derived from the ectoderm of the " neural plate." The distinction is also of importance with reference to the comparison of the type of lens found in the pineal eye of vertebrates with the forms of lens found in invertebrates, whether in the median or lateral eyes. It was maintained by some authors that the existence of a corneal or cuticular type of lens in the central eyes of certain arthropods and other classes of invertebrates put completely out of court any comparison of the " pineal eye " of vertebrates with the central eyes of invertebrates. A reference to the central eyes of Euscorpius (Fig. 95, Chap. 11, p. 133) or a section through an ocellus of a Dytiscus larva (Fig. 38) will show, however, that one type of lens formation can pass into the other ; and it is obvious that if the optic vesicle is withdrawn away from the surface ectoderm, as has occurred in the phylogenetic history of the pineal eyes of vertebrates, the cutaneous ectoderm or epidermis can no longer form or participate in the ontogenetic development of the lens of the " pineal eye," although it may have done so primarily. With reference to the ontogenetic development of the " pineal eye," Beard, who studied the pineal organ in the Ammoccete or larval form of Petromyzon, thought it possible that a portion of the cutaneous ectoderm might be included in that part of the neural tube which gives rise to the pineal organ, these cells being cut off at the time when the neural tube becomes separated from the surface, or cutaneous ectoderm. Whether this explanation is valid or not, it is quite certain that phylogenetically the neural ectoderm has been derived from the cutaneous ectoderm ; moreover, ontogenetically the neural ectoderm is continuous with the cutaneous ectoderm in the early stages of embryonic development. Further, there exist not only transitional forms between the types of lens developed from the optic vesicle and those derived directly from the hypodermal cells, but also it is quite frequent to find a cuticular or corneal lens combined with a vitreous lens formed from hypodermal cells in one and the same eye, e.g. in the larva; of Dytiscus or Acilius (Figs. 38 and 13).

A — Cup-like depression of the body epithelium which forms the primary optic pit.

B — Constriction of the mouth of the pit to form the primary optic vesicle.

C — Formation of the iris fold and primary cornea.

D — Development of the two halves of the non-cellular lens and the rampart-like outer fold which gives rise to the secondary cornea.

E — Further development of the secondary cornea, and formation of the anteriorchamber.

F — Section of the fully developed eye of Sepia officinalis, showing the retina, optic ganglion, optic nerve, various parts of the cartilaginous capsule, musclefibres, anterior chamber and the opening of the latter to the exterior :

ant. ch. : anterior chamber.

ap. : opening of anterior chamber to the exterior.

b.e. : body epithelium, which becomes the outer epithelial layer (Corpus

epitheliale externus). cap. : cartilaginous capsule. c. ep. : Corpus epitheliale.

e.l. : part of lens formed by the outer epithelial layer. i.e.l. : outer wall of optic vesicle, which becomes the inner epithelia

layer (Corpus epitheliale internus). i.f. : circular fold which becomes the iris. id. : part of lens, formed by the inner epithelial layer. mes. : mesenchyme. m.f. : muscle fibres.

o.f. : circular fold which forms the secondary cornea. opt.g. : optic ganglion. cp.n. : optic nerve. pig. I. : pigment layer of retina. rds. : rods. r.l. : inner wall of the optic pit, which becomes the retina.

(Redrawn from Lang's Comparative Anatomy.)

Fig. 37. A — Two isolated retinula; from the compound eye of a prawn, Palcemon squill a. (After Grenacher.)

retinula.

nuclei of retinular cells.

basement membrane.

optic nerve. rhabdome.

corneal facet. Semper 's cells, outer crystalline cone.

middle crystalline cone. cc" . : inner crystalline cone (hollow) pg. pg'. : pigment.

B — An isolated " crystal cone."

C — Transverse section of a retinula about its middle, bleached.

D — Transverse section of the posterior or inner end of the retinula.

Fig. 38. — Vertical Section through Ocellus of Larva of Dytiscus Mar ginalis, across its shortest diameter. (after gljnther.)

ect. : unaltered ectoderm. s.v.c. : short visual cell.

l.v.c. : large visual cell. s.v.r. : short visual rod.

l.v.r. : long visual rod. vitr. : vitreous mass secreted by n.f. : nerve fibres. perineural cells at mouth of pit.

In this connection it will be interesting to consider the capabilities of lens-formation from the cutaneous or surface layer of ectoderm and from the optic cup that have been demonstrated by experimental embryologists ; and also the influence of light and darkness on the contraction or expansion of melanophores and on the movements of pigment granules and pigment cells. Moreover, the multiplication of pigment cells that takes place in fish reared on a dark background as contrasted with others reared on a white background has a definite bearing on this subject.

Fig. 39. — Schematic Section through a Dorsal Eye of Onchidium, showing the Optic Nerve piercing the Retina, and its Fibres spreading out on its Inner Surface as in the Lateral Eyes of Vertebrates.

C. ep. : epithelium of cornea. op. n. : optic nerve.

C. ct. : connective tissue layer of pg. I. : pigment layer of retina.

cornea. r.b. : refractile body consisting of /. cap. : fibrous capsule of eye. two very large cells.

7i.f.l. : nerve-fibre layer of retina. s.c. : sensory cells of retina.

1 . Dependent differentiation of the lens vesicle. — An example of this is furnished by the differentiation of the lens from epidermis, which is dependent on the influence of the optic cup (Fig. 40). * See p. 174, Chap. 15.

1 O. Mangold (1929), Arch. Entw. mech., 117.

A piece of presumptive brain region from a Triton larva at the midgastrula stage was grafted into another Triton embryo at the same stage of development. The graft developed by self-differentiation into parts of the brain and an optic cup. This induced the formation of a lens from epidermis which was continuous with that covering the ventral part of the trunk of the host. 1

1 O. Mangold (193 1), Ergebn. der Biol, 7, after Spemann.

Fig. 40. - Dependence of the Development of the Lens on the Presence of the Optic Cup.

A — Triton larva into which a piece of presumptive brain region was grafted from another embryo of the same age. g. : graft which developed by selfdifferentiation into parts of the brain and an optic cup, which induced the formation of a lens /. from epidermis derived from the abdominal region of the host.

B — Transverse section through the same larva, showing the vesicle produced from the tissue of the host, v. ; a portion of the grafted brain, br. ; the optic cup, op. c, derived from grafted tissue ; sp. c. : spinal cord ; and pr. n. : pronephric tubules.

(After O. Mangold, from Elements of Experimental Embryology : Huxley and de Beer.)

2. Self differentiation. — The same author describes independent differentiation of the lens in Rana esculenta after extirpation of the presumptive eye rudiment at the early neurula stage (Fig. 41). The drawing shows a transverse section through the larva fourteen days after the operation. In other cases negative results were obtained or a small lens like thickening of the epidermis occurred in the situation in which the lens should have been developed if the optic cup had been present.

Fig. 41. — Self-differentiation of the Lens.

Transverse section through larva of Rana esculenta, fourteen days after extirpation of the presumptive eye-rudiment. A lens L. has developed, although no optic cup was present.

(From Huxley and de Beer, after Spemann.)

Fig. 42. — Lens formed from the Margin of the Optic Cup.

The presumptive eye-rudiment of an embryo of Triton was grafted into the side of the body of another embryo. The optic cup, not being in relation with epidermis, has formed a lens from its own margin.

Br. : portion of grafted brain tissue. L. : lens.

Int. : wall of intestine. Ep. : epidermis of ventral wall.

(From Huxley and de Beer, after Adelmann, Arch. Entzumech., 113, 1928.)

3. Lens formation from the edge of the optic cup. — The presumptive eye-rudiment of an embryo of Triton was grafted into the side of the body of another embryo and developed by self-differentiation deeply beneath the epidermis. Under these circumstances it gave rise to a lens which developed from the edge of the optic cup, as in cases of regeneration of an extirpated organ or part of an organ ' (Fig. 42).

The latter experiment is of particular interest with reference to the normal formation of a lens from a part of the optic vesicle as is the case in the eyes of many invertebrates and in the " pineal eye " of some fishes and reptiles ; although it must be born in mind that in the latter the lens is developed from the distal or superficial wall of the optic vesicle, which in the lateral eyes of vertebrates is invaginated to form the sensitive part of the retina. In the experimental Triton embryo the regenerated lens originated from the margin of the optic cup at the junction of the invaginated layer with the ensheathing or pigmented layer of the retina, and in the same situation as the vitreous or cellular, hypodermal lens of the Dytiscus or Acilius larvae (Figs. 4 and 13). Incidentally it may be noted that the pigment layer of the retina is in the same situation relative to the " regenerated lens " as the zone of pigmented hypodermal cells beneath the cuticle is to the vitreous lens of Dytiscus.

The Influence of Light in the Formation of Pigment and the Production of Physico-chemical Changes in the Superficial Layers of Epithelium

The whole question of lens formation and the specialization of refractileelements in relation with the receptive or sensory cells of the retina appears to be linked with the action of light on the cuticle and hypodermal cells of invertebrates and on the epidermis and the neuro-epithelial cells of the retina in vertebrates. This action is associated with the formation of pigment granules, also with chemico-physical changes and movement of the pigment granules within the cell-bodies and of the cells themselves. As is well known, the skin and subcutaneous tissues tend to become pigmented when exposed to light and pigment granules or pigment cells as a whole tend to move towards the source of light. This movement has been demonstrated in the pigmented cells of the retina in both vertebrates - and in vertebrates. •'• H. M. Bernard in 1896 suggested that eyes first arose as local modifications of tissue induced by the crowding of pigmented granules at spots in the skin which were most frequently and brilliantly illuminated. In the Q.J. Micro. Sc. (1896-7), 39, 343, he discussed differences in the structure of the median and lateral eyes of vertebrates and assumed that these different types of eyes of vertebrates must have arisen as modifications of two types of skin — the vestigial " pineal eye " being formed originally from a type of skin similar to that of the invertebrates, consisting of a single layer of palisade or hypodermal cells beneath the cuticle, which was supported internally by a layer of connective tissue ; whereas the lateral, paired eyes arose from the neural ectoderm and the stratified layers of squamous epithelium which form the epidermis of vertebrates, combined with the connective tissue components forming the outer tunics of the eyeball. He suggested also that the " pineal eye " " developed first as an optic pit from the skin of the ancestors of the vertebrates before that skin had assumed the vertebrate type, i.e. before the palisade layer had become protected externally by the mucous and horny layers." He also assumed that :

The retina is but a specialized portion of the epithelial layer of the skin, between the cells of which the pigment granules from the subjacent chromatophoral layer stream outwards under the influence of light.
The retina and the chromatophoral layer must have been in intimate and inseparable association through all the stages of evolution of the eye.

1 H. B. Adelmann (1928), Arch. Entzv. mech., 118.

2 L. B. Airey, J. Comp. Neurol, and Psychol., 25, 1915 ; 30, 1918. S. R. Detwiler, J. Comp. Neurol. & Psychol., 30, 1924. M. S. Mayou, Brit. J. Ophthalm., 1932, p. 227, and 1933, p. 477.

3 H. M. Bernard, Q.J. Micro. Sc, 39, 43, 47. G. H. Parker, 1899, Bull. Mus. Comp. Zool., 35, No. 6, p. 143.

43. — Section of an Eye of Arca barbata. (After Rawitz.)

ectoderm. r. : inner segment of cell containing

interstitial cell, mesoderm, pigment cell.

rod-like elements. v.c. : visual cell of retina.

He believed that simple eyes first arose in pigmented areas on exposed surfaces of the body in invertebrates, and that the action of light not only produced and caused movement of pigment granules, but that the irritation of the hypodermal cells resulted in the formation of slime. This slime, secreted as droplets either in the substance of the cell-body or making its way to the surface, was the first step towards lens-formation. Later certain of the hypoderm-cells became elongated and their cytoplasm becoming clear, they formed a cellular lens of the vitreous type (Fig. 43), or the clear viscous secretion of the cells formed a non-cellular vitreous lens of the type seen in certain molluscs : e.g. the limpet {Patella), in which a simple optic pit is present the cells of which secrete a viscous fluid into the hollow of the pit ; Trochus, in which the pit is converted into an unclosed vesicle, completely filled with highly refractile secretion ; and Murex (Venus 's comb), in which the secretion has become consolidated and shrunk away from the retina, thus forming a non-cellular spherical lens ; and the optic vesicle has become closed (Figs. 33-35). A " primary cornea " formed from the unpigmented distal segment of the optic vesicle and a " secondary cornea " derived from the superficial covering layer of hypoderm-cells and subjacent mesenchyme have also been evolved (Fig. 36, p. 50, and Fig. 121, Chap. 12, p. 164). These eyes, moreover show the differentiation of an outer clear refractile zone, a middle pigmented, and an inner nuclear-zone in the cells of the retina. In higher types of eye a specialization of individual cells of the retina is observed into refractile, pigment, and sensory cells (Figs. 11, 81, pp. 16, 119), and in many of the arthropods and insects these cells are grouped together into the separate units or ommatidia of a faceted eye (Fig. 37, p. 52).

The Pigment-cells of the Pineal Body

The occurrence of pigment in the pineal body is of interest not only from the light which it throws on the nature of this organ, but is of practical importance to the surgeon, as cases have occurred in which melanotic sarcoma l and other pigmented tumours have arisen in or in association with the pineal organ. The nature of the pigment contained in the human and mammalian pineal organ and its exact situation have been studied in detail by Quast - ; and pigmentation in the pineal organ of vertebrates in general, but more particularly cyclostomes and reptiles, by Beard, Dendy, Gaskell, and Studnicka.

As is well known, the colour of the skin in man depends chiefly on the presence in the skin of the pigment melanin. This is deposited as fine granules which are found in the cells of the stratum germinativum, more especially in its basal layer next the derma. As, in course of time, these deeper cells move towards the surface to replace the more superficial cells, the pigmentation becomes less pronounced, so that only a diffuse colouring of the epidermis is present in the stratum corneum. Besides the pigmented basal cells of the epidermis, large multipolar pigment-cells called melanoblasts are found beneath the epidermis in the superficial layers of the true skin. Their pigmented processes may extend for a considerable distance outwards between the cells of the epidermis, and the cells are characterized by a special staining reaction with the " dopa " reagent — 3.4-dioxyphenylanilin ' — while the pigment cells of the stratum germinativum or Malpighian layer, and the dermal chromatophores do not react. It is generally believed that the melanoblasts are modified epidermal cells, that they elaborate the melanin, and that this passes from them into the cells of the epidermis.

1 C. Ogle, " Sarcoma of the Pineal Body : Diffused Melanotic Sarcoma of the Surface of the Cerebrum." Trans. Path. Soc, London, 50, 4-6, 1898.

2 P. Quast, " Beitrage zur Histologic und Cytologie der normalen Zirbeldriise des Menschen," Zeitschr.f. mikr. anat. Forsch., Bd. 23, s. 335, 193 1.

In addition to the melanoblasts, cells bearing pigment and called dermal chromatophores are present in the connective tissue of the derma, and the areolar subcutaneous connective tissue. These are capable of amoeboid movement and are believed to serve as carriers of pigment which is formed elsewhere, e.g. in the melanoblasts. The pigment granules in these cells are larger and more irregular than in the basal epidermal cells and melanoblasts. Moreover, their distribution in the cell-body is not so even as in the epidermal melanoblasts. Pigment cells containing melanin which has actually been formed in the cell-body are, however, said by Maximow to occur, although rarely, in the derma, and have been named by him " dermal melanoblasts."

1 The Origin of Melanin. — Bloch, in 1917, demonstrated that the cells of pigmented regions contain a specific intracellular oxidase. He isolated from the embryo of the broad bean a substance, 3.4 — dihydroxyphenylanilin, which he called " dopa," and showed that it was readily changed by this oxidase into melanin. When this substance is added to the epidermal cells of skin in frozen formalin-fixed sections granules of melanin are formed — the " dopa " reaction. Bloch concluded that the colourless " mother-substance," or melanogen, is almost certainly closely related or identical with " dopa."

A large number of groupings in the protein molecule form coloured products on oxidation — tyrosine, tryptophane, phenylaniline — and it seems obvious that melanin is formed as an end-product from one of these chromogen groups. The colourless mother-substance is brought to the cell by the blood-stream ; here it meets the " dopa-oxidase " and is turned into the coloured pigment melanin.

Melanin is closely allied to adrenaline, and it is probable that the two substances are derived from the same precursors and form alternative end-products in metabolism. When the cells are stimulated to proliferate, so that there is an increase of the oxidative ferment, a pigmented tumour is the result or a general melanomatosis. When owing to cachexia or some dyscrasia of the adrenals these glands fail to utilize the chromogenic substance for the manufacture of adrenaline, an increase of pigment is the result, as is seen in Addison's disease, the effects of which are seen in the skin and even in the epithelial cells of the cornea ; and if there is no enzyme at all present, pigment cannot be formed and the condition of albinism results.

There is considerable difference of opinion with regard to the kind of cell in which pigment arises, thus : Recklinghausen believed that the pigmented cells of nsevi arise from the endothelium of the vessels. Unna held that pigmented cells were confined to the epithelia, and that the uveal pigment migrates from the retinal epithelium. Also, that malignant pigmented tumours are carcinomatous. Kornfeld showed that in the skin of frog embryos the subepithelial pigment sheet is formed by the migration of epithelial cells through the basement membrane into the corium. Krompecher held that the epithelial cells not only became morphologically similar to connective tissue elements, but also assumed their function, producing collagenous fibrils, a change which he termed " desmoplasia." Ribbert, on the contrary, contended that the pigmentation depended on a specialized connective tissue cell, the chromatophore, which was mesoblastic, and maintained that pigmentation and the formation of pigmented tumours were functions of the mesoderm. Pigment produced artificially by ultra-violet light appears in the deeper germinal layers of the epidermis. (Sir Stewart Duke-Elder, Extract from Recent Advances in Opthalmology , J. and A. Churchill, 1934, London.)

Like the pigment of the skin, the pigment of the eye may be considered under two headings, viz. (i) epithelial pigment and (2) the pigment present in connective tissue or mesenchyme cells. Thus both in invertebrates and vertebrates the pigment is chiefly found in the sensory receptive cells or in specialized epithelial cells of the retina, which either surround individual receptive sensory cells, as in the ommatidia of a composite faceted eye, or form a layer such as the external layer of hexagonal pigment cells in the retina of vertebrates. The connective tissue type of pigmented cell is found either in the form of " intrusive " mesenchyme cells among the sensory cells of the retina, as in the central eyes of the king crab {Limulus polyphemus), or in a definite layer in one of the tunics of the eyeball, e.g. the lamina chorio-capillaris, in which the spaces between the vessels contain a large number of branched cells of the chromatophore variety, or again in the anterior mesodermal layer of the iris. One of the principal functions of this pigment appears to be to screen off or to absorb superfluous rays of light. In the case of the iris in the lateral eyes of vertebrates, the pigment contained in the epithelial cells of the pars iridica retina; and the mesodermal anterior layer serves by means of the sphincter and dilator pupillge muscles to regulate the amount of light entering the eye through the pupil. The iris thus serves as a movable curtain which not only prevents oblique or circumferential rays entering the eye but controls the number of rays which fall upon the central part of the lens and more sensitive portions of the retina. In those animals in which the eye is not provided with a movable iris, pigment is nevertheless deposited in a circular zone round a transparent area of the skin or cuticle, which area serves as a cornea (Fig. 107, Chap. 12, p. 149). The clear area surrounded by a rim of pigment will allow the passage of a beam of light to any particular part of the retina, from approximately one direction only, and an indistinct image will be formed, the direction of which is well indicated, but there is often no means of focusing this image or regulating the amount of light entering the eye : such eyes are represented by the eye of Nautilus (Fig. 112, Chap. 12, p. 152), or the eyes round the edge of the pallium in the Scallop (Pecten) (Figs. 106, 107, Chap. 12, pp. 148, 149). The same type of simple upright eye is also seen in the " pineal eyes " of cyclostomes and reptiles, in which a clear area free from pigment lies immediately over the pineal organ. Incidentally, it may be mentioned that pigment is sometimes present in the part of the pineal vesicle which gives rise to the lens, both in cyclostomes and in some reptiles, e.g. the blind worm, Anguis fragilis. The pigment found in this situation is probably a degenerative product, and indicates the vestigial nature of the " pineal eye."

Quast distinguishes two kinds of pigment in the pineal gland of man. Yellow pigment, present in the cells of the parenchyma, which results from the wear and tear or breaking down of the parenchyma cells — " Abnutzungspigmente " ; and black pigment, or melanin, which is found in the interstitial tissue. 1 The characteristic features of these are contrasted in the following table :

Yellow Pigment Black Pigment

Parenchymal pigment. Waste Pigment of the membranes and of the

pigment. interstitial tissue. Melanin.

1 . Irregular masses of granules of 1 . Granules almost always of approxi different size often clumped mately the same size, and of

together. uniformly spherical form.

2. Granules rather coarse. 2. Fine granules.

3. Clear, glistening, yellow-brown 3. Dark brown colour.

colour (though in aged subjects it may take on a deeper tone which does not differ much from the pigment of the interstitial tissue).

4. Feebly stainable. 4. Relatively deeply stainable.

5. Stains with basic dyes, especially 5. Does not stain with basic dyes, after the removal of fat or either before or after bleaching, bleaching.

Quast describes varying degrees of pigmentation of the parenchyma cells, and emphasizes the extreme fineness of the pigment granules found in the interstitial tissues, more especially in some of the branched pigment cells and elongated cells following the course of the larger vessels in the connective tissue septa and in the connective tissue of the membranes (investing layer of pia mater). Quast, referring to a case of primary melanotic sarcoma in the epiphysis of a woman aged 32, states that Ogle described the normal pineal gland as containing only a very small amount of melanin pigment, but not so small as to exclude the growth of a primary melanotic tumour. In the case described the pigment was of a brown colour and distributed in the parenchyma cells of the gland. The primary presence of pigment in the epiphysis, according to Ogle, is otherwise only to be seen in cases of cystic degeneration. Although pigment is scanty in the normal pineal body in man, it is abundant in the cells and connective tissue of the pineal in the horse and ass.

1 With reference to the use of the term " interstitial tissue " as denoting the supporting tissue of the " parenchyma cells," it is necessary to state that this is a complex tissue composed largely of a glial reticulum which is epithelial in origin, but also containing connective tissue elements, derived from the pia mater investing the pineal organ and carried into its substance by the vessels.

Quast concludes by stating that " the pigment cells of the interstitial tissue are, on morphological grounds, to be regarded as chromatophores. The chromatophores contain only one kind of pigment, melanin. The pigment of the interstitial tissue of the pineal considered from every aspect, namely from its morphological, physical, and optical characters, including its microchemical and staining reactions, belongs to the mesodermal, melanin type."

With reference to the parenchyma pigment he states that the older the patient the greater the pigment content of the parenchyma.

The morphological significance of the type of pigment found in the pineal body of mammalia lies in the indications that it may give, first, as to whether its presence may be regarded as evidence of its vestigial nature, namely, whether a particular kind of pigment indicates the derivation of the epiphysis from the " pineal eye " of lower types of vertebrates ; or, secondly, whether it throws any light on the view, maintained by some authors, that the mammalian epiphysis is a newly evolved glandular structure, which differs in structure and in function from the parietal organ of cyclostomes, reptiles, and Amphibia. Again, whether the presence of pigment in the organ is merely incidental, being derived from the pia mater covering the organ, or results from degenerative processes occurring in the parenchyma cells of the gland, which processes are comparable to the katabolic products of actively secreting glands.

Like Quast, who studied the pigment of the mammalian epiphysis, Ley dig, working on the " pineal eye " of reptiles and cyclostomes, distinguished two kinds of pigment. The one present in small amount and having the dark (brown-black) type of granule, the other when seen with transmitted light having the dusky-yellow granule, which corresponds closely to the guanin-containing pigment of the skin. With reflected light these granules in the retinal cells of the " pineal eye " of cylostomes appear white. The latter type of pigment was in Leydig's opinion comparable with pigments containing uric acid. Studnicka confirmed Leydig's opinion of there being two types of pigment in the "pineal eye " of cyclostomes : there being a small amount of pigment consisting of fine granules widely separated from one another and of a dark brown colour found in the supporting tissue of the retina, this latter type being clearly seen in preparations from which the " white pigment " had been removed.

Concerning the nature of the white pigment seen in the " pineal eye " of cyclostomes, there is a considerable difference of opinion with regard to its true nature. Thus, according to Studnicka, Mayer in 1864 stated that the epiphysis of Petromyzon contained many concretions of lime. Ahlborn considered the small white corpuscles to be a special white substance, which he described as white pigment somewhat similar to the " brain sand " of higher vertebrates, and thought that the substance with which they were dealing might be calcium phosphate.

These small corpuscles compactly fill the retinal cells, and they give, with reflected light, a snow-white appearance to the organ. When it is deposited in large masses, so as not to be transparent, it appears on examination with the microscope by transmitted light to be a deep black, which circumstance has, according to Studnicka, given rise to many erroneous statements, certain authors having described the retina as being filled with black pigment. The substance, however, was observed by Gaskell and also Studnicka to be completely removed from specimens fixed in Perenyis fluid, which contains nitric acid, and also from specimens fixed with picric acid. Under high magnification, Studnicka observed the material in the form of separate pigment granules. These varied in size, were round or oval in form, with well-defined, sharp contours. In his opinion they are present in the protoplasm of the retinal cells and not on their surface, as maintained by some authors. These granules are present also in the ganglion cells, which, when they are completely filled, have the appearance of irregular clumps of pigment. Finally, in the deepest part of the retina, many of the pigment corpuscles are found in the intercellular tissue, in the wall of the atrium, and prolonged into the pineal nerve. The pigment is absent in the larval form, or ammocoetes, when smaller than 50 mm. in length. In older ammocoetes it is generally present, and it is always present in the adult animal. The absence of the pigment in the young ammocoetes and its absence in specimens prepared with acid fixatives have given rise to the view expressed by certain authors that the pigment is present in some species of Petromyzon, but is absent in others. Gaskell maintained that the " brain sand " so commonly present in the human pineal organ was not only an indication of its vestigial nature, but that it also pointed to the mammalian " epiphysis " being derived from the " pineal eye."

It will be of interest to mention here that white pigment has also been described in the eyes of invertebrates. Thus G. H. Parker figures in Gammarus " accessory " retinular cells, which lie outside the pigment cells that surround the clear axial rod or rhabdome. These cells are said to contain white pigment, which Parker believed had the function of reflecting rays of light back to the central part of the rhabdome, when this was exposed by retraction of the black pigment away from the central segment of the rhabdome (Fig. 44). It may be presumed that this action of the white pigment would come into play when the eye was exposed to a dim light, and compensate in a measure for the loss of a bright illumination. Whether it is of the same nature as the white pigment of the " pineal eye " of Petromyzon has not been demonstrated, but the presence of " white pigment " and " black pigment " in well-defined and constant positions in the cells composing the retinulae of the compound eyes of the same animal indicates that the appearance of black pigment in Gammarus ornatus is not merely due to the deposit in the retinal cells of concretions of phosphate of lime, which on examination with the microscope by transmitted light appear black, as has been said to be the case with the white pigment in the pineal sense-organ of Petromyzon. In Gammarus the white pigment of the " accessory cells " when viewed by transmitted light appears as glistening refractile granules, not black. These " granules," according to Parker, are not subject to the photochemical changes which occur in the pigment cells which ensheath the colourless rhabdome, and he suggests that " the accessory [white] pigment cells probably act as reflecting organs and in very dim light turn such rays as have escaped laterally from the rhabdome back again into that structure, thus aiding in an effective stimulation of this organ." Parker's description of these two kinds of pigment contained in separate cells lying adjacent to one another, one subject to physico-chemical changes produced by exposure to light and the other merely serving as a reflecting mechanism, suggest that the " black " granules in the dark cells are true pigment granules containing melanin, while the granules of the " white " accessory cells are possibly due to a fine crystalline or crystalloid deposit in the cell substance.

Fig. 44. — Gammarus Ornatus (Freshwater Shrimp). Photochemical Changes in the Retinal Pigment of Gammarus. (Aeter G. H. Parker.)

Changes due to exposure to light are limited to the black pigment in the middle and proximal portions of the retinular cells, they are not observable in the accessory pigment cells (white pigment).

A — Specimen fixed after exposure to light. The pigment has left the body of the cell and has accumulated round the rhabdome.

B — Transverse section of retinula through region of rhabdome.

C — Longitudinal section through the retinula when light has been excluded.

D — Transverse section through the retinula when light has been excluded.

ac. c. : accessory retinal cell.

b.m. : basement membrane.

con. : crystalline cone.

cl. cm. : corneal cell.

cl. rt.n. : central retinal nerve cell.

cm. : cornea.

n. ac. c. : nucleus of accessory cell. n. rt. n. : nucleus of retinal nervecell. rhb. : rhabdome.

-> <- Arrows indicating the level of the transverse sections B and D.

The variability in the colour of eyes is a subject of great interest and importance. The eyes of many invertebrates are red. Thus in the Protozoan Euglena viridis, which is commonly found floating on the water of ponds and gives to this a bright green colour, the eye-spot or " stigma " is- a vivid red, in contrast to the general green colour of the body. The red colour is said to be due to a pigment allied to chlorophyll and called haematochrome. In some orders of the coelenterates, the ocelli or eye-spots, arranged round the umbrella, appear as brilliant dots of colour, orange or red, sometimes phosphorescent.

Among the Annelida, or ringed worms, Andrews ' has described in Tubicola potamilla highly differentiated compound eyes of a bright orangered colour on the sides of the branchiae. This animal lives in a leathery tube which is seen projecting from holes in gasteropod and bivalve shells. From the end of this tube cephalic, branchial plumes expand as a circular series of radiating stems, each bearing two rows of branchial filaments which are in the fully expanded state, directed forward. The eyes are on the posterior or outer sides of the main stems, there being rows of three to eight on each of the 20 stems. Each eye is a convex hemispherical protuberance on the outer side of the main stem. On section the eyes are seen to consist of radiating groups of cells, resembling the ommatidia of compound eyes of insects and Crustacea. The cells are differentiated into sensory cells and pigment cells, the former, in relation with clear refractile elements, ending distally in a conical inclusion of vase-shaped form, similar to the " crystal-cone " of certain composite eyes, e.g. the paired eyes of Apus. The eyes lie in close relation to nerve fibres and ganglia, and although a direct connection between the sensory cells and the nerve fibres has not been traced with certainty, the eyes have been shown experimentally to be very sensitive to light. Thus the shadow of a hand held over an aquarium containing the Tubicola will cause instant retraction of the filaments. These eyes have been found in other species, e.g. P. oculifera, and it is thought that they may be of some interest in interpreting the mode of development of the eyes of arthropods.

1 E. A. Andrews, J. Morph., 5, p. 271, 1891.

The Pigment in the Eyes of Insects, Arachnids, and Crustacea

The deposit of pigment in the form of small, dark-brown granules of approximately uniform size in the hypoderm or epithelial cells and of coarse granules in branched mesenchyme cells is very like that found in the eyes of vertebrates. Moreover, in the more highly differentiated eyes of species belonging to these three classes, there is a differentiation into separate sensory-cells and pigment-cells. There is also frequently a more abundant deposit of pigment in the immediate neighbourhood of the eyes, but absence or reduction of pigment in the region of the lens. On the other hand, in the composite eyes each rhabdite or crystalline-rod or crystalline-cone is usually surrounded and isolated from its fellows by specialized pigment cells. Further, the pigment cells of the retina in many species are of two types, namely, (i) epithelial, and (2) pigmentbearing, " intrusive " mesenchyme cells, which are elliptical or multipolar in form and are believed to have wandered into the retinal zone from the exterior, as in the medial or central eyes of Euscorpius and Limulus polyphemus (Fig. 95, Chap. 11, p. 133 and Fig. 87, p. 125).

Pigmentation of the Eyes of Molluscs

The same characteristic features are present with regard to the deposit and distribution of pigment in the eyes of molluscs as in the arthropods and vertebrates, namely (1) a uniform deposit of small, deep-brown granules in the epithelial cells — including the hypoderm cells and inner layer of columnar retinal cells ; (2) an irregular deposit of granules of unequal size in branched or fusiform mesenchyme cells. The deposit in the tall columnar cells of the retina is, moreover, usually confined to the middle third of the cell, while the inner end of the cell which is turned towards the light is clear, as in the eyes of Patella, Trochus or Murex (Figs. 33-35). This distribution of the pigment in the cells of the retina is similar to that found in the retina of the parietal eye in some reptiles, e.g. Anguis and Pseadopus Pallasii. It must be borne in mind, however, that although the resemblance in the distribution of pigment and the general disposition of the cells of the retina in the examples given is very close, these eyes differ in other respects and cannot be regarded as homologous. But the close resemblance in minute structural details, with regard to the deposit of pigment in two types of cell and the similarity of its disposition in the eyes of widely different classes of animals, does point to a general homology with regard to histological structure among these classes — a point which is fully corroborated by resemblances in histological structure which occur in other tissues.

Pigmentation of the Eyes of Vertebrates

This subject may be considered under two headings :

1. Pigmentation occurring in the pineal organ.

2. Pigmentation of the lateral- or paired-eyes.

Pigmentation of the pineal apparatus may further be considered in two sections, namely :

A. Pigmentation of the parietal sense-organ, or " pineal eye," and the accessory structures connected with it.

B. Pigmentation of the " epiphysis," conarium, or " pineal gland." Commencing with the description of the pigment found in the pineal

eyes of cyclostomes, we have to distinguish between the pigment found in the retina of the parietal sense-organ and that which is found in the tissues surrounding this. The pigment cells of the retina are distinct from the sensory cells and have been accurately described by Dendy in the late velasia stage of the New Zealand lamprey — Geotria (Fig. 45). They are long, tapering cells, having a wide inner end directed towards the cavity of the vesicle. The free end of this inner segment is rounded in form and marked off from the body of the cell by a clear line which corresponds in position to a limiting membrane ; this membrane can be clearly seen in depigmented specimens. The nucleus is oval and situated near the outer end of the cell ; beyond this, where the cell divides into thin tapering processes, pigment granules are absent. The granules are almost uniform in size and appear dark-brown or black by transmitted light. Pigment cells are not found in the left parietal sense-organ — " parapineal organ " of Studnicka — and they are absent in the single parietal sense-organ of the hag fish, Myxine glutinosa.

The appearance of the pineal region of an adult lamprey, P. planeri> as seen from above is indicated in Fig. 47, after Studnicka. This author describes the whole triangular area shown in the figure as the " parietal cornea " or " Scheitelfleck " (parietal-spot). He defines the cornea as comprising all the layers between the pineal organ and the surface of the head. It has a " glass-like transparency " and consists of, first, a thin fibrous layer, continuous with the cranial wall, and, next, the eye. This is convex towards the surface. Superficial to it is a conical mass of transparent mucoid tissue — the " parietal plug " of Dendy (Fig. 134, Chap. 17, p. 188). Over the mucoid tissue lie the corium and epidermis. The branched pigmented cells of the surrounding corium are completely absent over the pineal organ, and the pigment cells of the epidermis are much reduced here both in size and number (Fig. 134, Chap. 17, p. 188). The whole area thus appears pale as compared with the surrounding skin. In the middle of the parietal cornea is a circular white spot (" weissen Scheitelfleckes ") produced by the retina of the parietal organ which is seen shining through the cornea. Dendy describes the appearance of this minute central area in the New Zealand lamprey, when seen from above (Fig. 47), as a white rim enclosing a central spot, the latter lying directly over the " pellucida " or " lens." The white rim is due to the white pigment of the retina (? phosphate of lime) shining through the transparent cornea.

Fig. 45. — Parietal Sense-Organ of Geotria, the New Zealand Lamprey. The Stage represented is of the Sexually Immature Form, " Velasia Stage." (After Dendy.)

Sagittal section of the right parietal eye (slightly diagrammatic) showing the general structure of the organ.

At. : atrium.

C.T. : connective tissue.

G.C. : ganglion cell.

I.S.P.C. : inner segments of pigment cells.

N.C.C. : nuclei of columnar cells of pellucida.

N.S.C. : nuclei of sense cells.

O.S.P.C. : outer segments of pigment cells.

P.N. : pineal nerve.

P. Str. : protoplasmic strands in interior of vesicle.

Pell. : pellucida.

Ret. : retina.

Fig. 46. — Parietal Sense-organ of Geotria, as in Fig. 45.

Diagram showing the minute structure of the retina ; on the right side the pigment

is represented, on the left the cells as seen when the pigment has been removed. Lettering as in Fig. 45, in addition : C.T.C. : connective tissue cell. I.S.P.C. : inner segment of pigment

cell. L.M. : limiting membrane. N.F.N. : network of nerve-fibres. N.P.C. : nucleus of pigment cell.

N.S.C. : nucleus of sense-cell. O.S.P.C.: outer segment of pigment

cell. R.S.C. : retinal sense-cell. S.C.K. : terminal knobs of sensory

cells of retina.

The appearance of a central spot inside the white rim is due to the interposition of the lens between the cornea and the retina, obscuring a direct view of the central part of the retina. In reviewing these points we may note that : when the pineal eye is removed and the parietal cornea is then viewed from above, the central white area has disappeared ; and if the parietal cornea is held up to the light, the area is seen to be translucent. When sections of the pineal eye are examined with the microscope by transmitted light, the white pigment contained in the retinal cells of older specimens is found to be absent in young specimens or specimens which have been fixed in acid-containing fluids . In adult specimens or late larva; fixed in alcohol or other preservative not containing acid, the " granules (? phosphate of lime) appear as minute spherical bodies evenly distributed through the inner and greater part of the outer segment of the cells " (Dendy).

Fig. 47. — The Head of an Adult Lamprey, Petromyzon p/aneri,

SEEN FROM ABOVE ; SHOWING THE PARIETAL Area and Parietal Spot (p.s.) (After Studnicka, 1893-)

Fig. 48. — The Pineal and " Parapineal Organs " (Right and Left Parietal Eyes), as seen from above under a disSECTING Lens. (After Dendy, 1907.) R.P.E. , L.P.E. : right and left parietal eyes. Geotria.

The inheritance of a negative character, such as the generalized absence of pigment in albinism or the absence of a particular constituent of the blood or of a ferment such as prothrombin in cases of haemophilia, is well known ; but the inheritance in living animals of a localized absence of pigment in connection with the vestige of what presumably was once, in animals belonging to the palaeozoic period, a functional organ, is a problem of the greatest interest, and the solution of this problem appears to be as difficult and as remote as many other problems relating to pigment distribution and the inheritance of pattern.

A significant exception to the absence of pigment in the region of the " parietal scale " occurs in the wall-lizard {Lacerta muralis), in which pigment has been shown by Leydig not only to lie beneath the parietal or corneal scale but even to encroach on the clear central spot which lies immediately over the pineal organ. This change is evidently a secondary one, and is probably due to the need for pigment in this situation in a type of animal frequently exposed to the heat of the sun and lacking any protective covering in the way of hair or feathers. The present needs of the animal in this case have apparently overcome the inherited bias towards lack of pigment formation in the pineal region, but it is possible or, indeed, probable that the pigment figured by Leydig is not actually formed in or under the corneal scale of the lizard, but has been carried into the region by chromatophores from the surrounding tissues ; if this is the case, the hereditary lack of pigment formation in the area still exists, but it has been countered by the migration of pigment cells into the deeper layers of the cornea.

Pigmentation of the Pineal Region in Fishes

The parietal sense-organ, or " pineal eye," is generally thought to be absent in living classes of fishes ; though it is possibly represented in some by the expanded end- vesicle of the pineal organ. Notwithstanding the absence of the parietal sense-organ, there is frequently a parietal foramen, or a parietal canal or pit, closed externally but opening into the cranial cavity internally (Fig. 49). This lodges the " end- vesicle " and distal part of the stalk of the pineal organ. Over this area is a pigmentfree area of the epidermis and corium. In the spiny dog-fish {Spinax niger), the " Scheitelfleck " is very conspicuous, although no true parietal cornea is present, like that of the cyclostomes and certain reptiles. It appears as a pale area in the parietal region, which contrasts sharply with the deeply pigmented skin surrounding it. This area is separated by a considerable thickness of loose, subcutaneous tissue containing the tubular organs, or ampullae of Lorrenz, and it is completely separated from the pineal organ by the cartilage closing the parietal canal.

In some fishes, e.g. Raja clavata, the stalk of the pineal organ is accompanied throughout its whole length by a sheath containing bloodvessels ; this shows an intensive degree of pigmentation, especially around the large dorsal vein, which is wider than the diameter of the end-vesicle itself.

In the spoonbill, Polyodon (Fig. 50), a lozenge-shaped parietal plate is present over the end-vesicle of the pineal organ, and the skin over this, as in Spinax, is destitute of pigment. The general relations of the pineal organ to the cranial wall are very similar to those of Spinax.

Very few allusions are made with reference to the existence of pigment in the cells of the end-vesicle or the stalk of the pineal organ of fishes, and it seems probable that pigment is not generally present in the endvesicle of fishes. Although from the developmental standpoint the endvesicle appears to represent the part of the primary pineal diverticulum

Fig. 49. — The Pineal Organ of an Adult Spinax Niger, seen in Longitudinal Section, and showing the Relations of the Surrounding Structures.

(From 5>tudni

cka.j p IG 50 — Dorsal As

amp

L. : ampulla of Lorrenz.

pect of the Head of

cor.

• corium.

a Spoon Bill, or

cp. :

posterior commissure.

Paddle Fish (Pol

cr. :

cranial wall.

YODON FOLIUM), A

ds. :

dorsal sac.

North - American

epd.

epidermis.

Fresh-water Fish

h.c. habenular commissure.

of Primitive Type

hm.

hemisphere.

ALLIED TO THE

nib.

• midbrain.

Sturgeons and

pa. .

paraphysis.

showing a Well

po. .

end-vesicle of pineal organ.

marked Parietal

p.p.

mouth of parietal pit.

Plate and Parietal

st. :

stalk of pineal organ.

Spot. (R. J. G.)

which gives origin to the " pineal eye " of cylostomes, and of certain Amphibia and reptiles, it evidently does not differentiate so far as to represent the parietal sense-organ of these animals, and a retina with sensory, ganglionic, and pigment cells is not differentiated.

Pigmentation of the Pineal Region of Amphibia

Little has been recorded about the presence of pigment in the pineal organ of Urodeles. Eycleshymer (1892), however, alluded to the presence of pigment in the inner ends of the cells, forming the many-layered inner wall of the hollow epiphysis in Ambly stoma mexicanum, and according to Galeotti (1897), in Proteus anguineus pigment granules are present in its very small pear-shaped epiphysis. The pigment granules are situated in special cells in the neighbourhood of the nucleus, and he states that this is the only place in the brain of Proteus in which pigment is present.

In the Anura, or tailless amphibians, the allusions to the presence of pigment and its situation with reference to the parietal sense-organ (Stieda's frontal organ) and the epiphysis are much more definite than is the case with the tailed amphibians. Thus, the " parietal spot " was accurately described by Stieda in 1865 : " There is to be seen a slight bulging of the skin on the top of the head, between the lateral eyes. When the skin lying over the organ is removed, the spot is seen to be transparent ; this being principally due to the absence of pigment. The corium surrounding the pigment-free area (parietal cornea) contains an abundance of pigment. A small amount of pigment is, however, present in the epidermis over the frontal organ. The epithelial glands are absent or are reduced in size and number in this region."

The parietal spot is not equally distinct in different examples of the same species and it is absent in many allied species. Thus, according to Leydig, it is best marked in Rana fusca, whilst in Rana arvalis and Rana agilis only traces are visible and in some specimens it is entirely absent.

The position of the end vesicle in Bufo is indicated by a clearly defined white spot. In Bombinator the pigment layer and glands are totally absent in the corium over the vesicle ; the epidermis here is, however, strongly arched upwards and its outermost layer is prolonged into a long, deeply pigmented black horn. In Alytes obstetricans, the midwife-frog, the pigment layers of the corium and epidermis over the vesicle are as well developed as in the surrounding skin.

With regard to pigment in the " frontal organ " (Stirndriise, endvesicle), Leydig states that the organ contains pigment in Bombinator, but that in frogs the frontal organ is devoid of pigment.

Pigmentation of the Pineal Organs of Reptiles

The highest degree of development and differentiation of the parietal sense-organ and " pineal sac " in living animals is preserved in this class, more particularly in Sphenodon and certain lizards, in which the general structure of the organ has been mostly minutely studied, and in which it is believed to function at any rate as a light-percipient organ and possibly be of some use to the animal. On the other hand, both parietal senseorgan and pineal sac are absent in the Crocodilia, although habenular and posterior commissures are present. The pigment, as in other classes of vertebrates, is of two types : (1) epithelial, in the form of fine, darkbrown granules, present in the cylindrical cells of the retina, and in the large, round ganglion cells (pigment balls) and also in the epidermis of the skin, except directly over the parietal scale ; (2) mesodermal, the granules of which are contained in branched cells, around the sheaths of the parietal organ and pineal sac, more especially in relation with the blood-vessels and in the subcutaneous tissue. The details of distribution of the pigment in the cells of the retina will be dealt with later in the description of the pineal eyes of Sphenodon and of different types of lizard, and it will only be necessary here to allude to certain general points :

The variability in the degree and distribution of the pigment in different orders within the same class.
The similarity in the distribution of the pigment within the retinal cells to that in the eyes of many invertebrates.
The presence of pigment in the wall of the pineal sac or end vesicle of the epiphysis in the same situations as in the retina of the parietal sense-organ (" pineal eye ").
The presence of pigment in " accessory parietal organs " in the same situation, e.g in Pseudopus Pallasii, with other evidence suggests the primary double nature of the organ — the apical part of one member of the pair being ordinarily suppressed, but occasionally appearing as an incompletely differentiated senseorgan ; this organ, however, possesses structural peculiarities which agree even in such details as the distribution of pigment in the cells of the retina, and render its identification as a parietal sense-organ almost certain.

Pigmentation of the Pineal Region in Birds

Klinckowstroem (1892) described a peculiar pigmented outgrowth from the surface of the head, opposite the epiphysis, in certain swimming birds, which he considered to indicate the site of a former parietal spot.

He found this vestige of a parietal spot in only 12 cases out of 200 embryos examined by him. These were in : Sterna hinmdo, the swallowtern (1 ex.) ; Larus marinus, the black-backed sea-gull (4 ex.) ; Larus canus, the common gull (2 ex.) ; Larus glaucus, the green gull (4 ex.) ; and Anser brachyrhynchus, the pink-footed goose (1 ex.). In the adult birds he found nothing special in the region of the parietal spot.

The outgrowth consists of a small, dome-shaped projection on the surface of the head, which appears before the development of the featherpapilla;, opposite the point towards which the apex of the pineal diverticulum is directed. The epidermis is raised above the level of the surrounding skin. In this situation there appears at the same time a remarkable accumulation of pigment, both in the epidermis and the subcutaneous mesenchyme. The cupola-like projection later divides into two small hillocks. Still later, the parietal spot becomes surrounded by a circle of feather-papillae. Finally, the area is invaded by the ingrowth of small feather-papillae and it eventually disappears. Studnicka, in commenting on these observations, mentions that he has himself heard of a case in which a parietal foramen was present in the skull of an adult goose, and that a round hole closed by connective tissue is found in the roof of the skull of adult geese, more especially in those varieties which possess a crest. This hole lies just in front of the point where the epiphysis ends, and he states that it can have no other significance than that of a parietal foramen. The occasional appearance of this embryonic vestige in the abovementioned varieties of sea-gull and allied species of bird and of the parietal foramen in the skull of adult geese is especially interesting as the parietal foramen is usually absent in the skulls of birds, notwithstanding the high degree of development of the pineal body. The pigment spot and the occasional presence of a parietal foramen in these birds serve as an indication of the previous existence of a parietal sense-organ in the ancestors of birds and of the identity of the avian epiphysis, or proximal part of the pineal apparatus, with the more fully evolved organ which is present in certain living reptiles, such as Varanus and Sphenodon.

Pigmentation of the Pineal Organ in Mammals

We have already referred to the work of Quast, p. 62, on the pigment of the human pineal organ. All authors appear to be agreed that in the mammalian pineal organ pigment is contained in two types of cell : (1) the parenchyma cells, (2) branched or elongated cells which are present in abundance in the capsule and interlobar septa following the course of the vessels. The latter often appear to be stretched out over the vessel walls and to lie in the perivascular spaces. There is, however, considerable difference of opinion with respect to the colour of the pigment granules in the two types of cell, and it seems probable that considerable variations occur in the depth of colour between pale yellow and dark brown, or even black, which are due in part to age and in part to different methods of preparation. The close association of the branched or elongated pigment cells with the blood-vessels, which is especially evident in the horse, has given rise to the opinion that the situation of the pigment often in fine streams resembling nerve-fibres, along the course of the vessels, may indicate the route which is taken by secretions leaving the gland, it being suggested that these make their way from the spaces of the reticulum into the perivascular spaces and veins along the course of the pigment granules.

The pigment which occurs in eyes, whether vertebrate or invertebrate, is concerned not only in the reflection or absorption of light, or, as in the iris, the screening off of superfluous rays, but it may also be developed in other situations than the eye or its immediate neighbourhood as a means of attraction or sometimes detraction. An example of the latter is found in the spots of dark pigment known as " false eyes " seen on the sides of certain fishes near the tail, which probably serve to distract attention from the true eye and more vital parts of the body. Pigment, moreover, is not always developed for a useful purpose, but may be formed as a waste product in a degenerating organ, as is the case in the lens of the pineal eye of certain lizards, e.g. the blind-worm {Anguis fragilis). Moreover, the deposition of pigment in the retinal cells of the pineal organ may occur as an inherited character, although the need for this pigment has, according to geological evidence, ceased millions of years ago. The clinical importance of the occurrence of pigment in the pineal body in the human subject lies, as previously mentioned, in the possibility of a melanotic sarcoma arising in this organ. The presence of light brown or yellow pigment granules in cells of glial type or the branched connective tissue cells around the vessels and in the capsule or the interlobar and interlobular septa appears to be one of many indications of the vestigial nature of the organ, more especially as the amount of this type of pigment is greater in specimens obtained from aged individuals than in the pineal bodies of young children or infants.

Pigmentation of the Lateral Eyes of Vertebrates

The situation and types of pigment found in the lateral eyes of vertebrates are so well known that we do not propose to do more than allude to this aspect of the general question. Broadly speaking, the two types of cell in which pigment is deposited or formed, namely (1) epithelial and (2) mesodermic, resemble the same two types of cell in the pineal organ and in the eyes of invertebrates. There are some points of interest, however, with reference to the development of pigment in the lateral eyes which have a bearing on pigmentation in the pineal organ, and we shall therefore give a brief account of the development of pigment in the human eye. This subject has been recently studied by Ida Mann. 1

1 Ida Mann, Development of the Human Eye, Cambridge University Press, 1928.

Minute pigment granules of a golden-brown colour first appear in the neuro epithelium which forms the outer wall of the optic cup in human embryos at the 8-io-mm. stage of development. They are deposited at first in patches or small groups in the cytoplasm between the nucleus and the inner margin of the cell, namely the border of the cell next the cleft between the outer and the inner walls of the optic cup, which represents the original cavity of the primary optic vesicle. By increase in number of the granules they soon completely fill the inner part of the cell, whereas in the outer part of the cell the granules are fewer in number and with low-power magnification this part of the cell appears clear. A significant circumstance is that the deposit of pigment in the outer wall of the cup appears at the same time as the development outside it of the plexus chorio-capillaris. At first the plexus is in close relation with the neuro epithelium ; later, however, at the 14-mm. stage of development, a continuous clear membrane, the membrane of Bruch, is formed between the epithelium and the choroid. It is probable that this membrane would prevent the passage of pigment granules from choroid to epithelium, but would act as a dialysing membrane with reference to the fluid constituents of the pigment, namely tyrosin, which has been shown to be converted into melanin by the action of the ferment tyrosinase. Little is known with regard to the formation of pigment granules, but it seems probable that these are developed in the cytoplasm of epithelial cells

(Fig. 51), and grow to a definite size and shape ; and that the relation of

the colouring matter to the granule is much the same as that of haemoglobin

to a blood corpuscle — that is to say, under ordinary circumstances the

colouring material is carried by the granule, but it may under certain

conditions escape from the granule and become diffused in the cytoplasm

or intercellular spaces. Returning to the further development of the

pigment layer of the human retina : this continues and remains throughout

life as a single layer of cells, which in the definitive form are seen to be

hexagonal when viewed in tangential sections and of an oblong

quadrangular shape in sections made vertical to the surface. The inner

end is prolonged into delicate, tapering processes which surround the

outer ends of the rods and cones. These are specially well seen in the

retina of certain fishes and Amphibia, in which the pigment granules

appear as minute oval plates arranged in series and in parallel rows, their colour when seen by transmitted light being a resinous-brown or amber tint. The two layers of the optic cup are each carried forward as a single layer of cells beyond the ora serrata, on to the inner or posterior surface of the ciliary region and iris, as the pars ciliaris retinae and pars iridica retinae. The outer or anterior layer of the pars ciliaris retinae only is pigmented, and this is the case in the early stages of development of the pars iridica retinas, the outer layer being pigmented, the inner posterior layer being at first destitute of pigment, but gradually becoming pigmented between the end of the third month and the seventh month. The deposit commences at the margin of the pupil extending from the anterior layer round the marginal sinus, and then outward in the posterior layer as far as the bases of the ciliary processes ; beyond this the pigment ceases to extend, and in the adult the posterior layer of the pars ciliaris retinae is unpigmented.

The mesodermal pigment of the choroid appears later than the ectodermal retinal pigment, about the beginning of the fifth month. The pigment is found in irregularly branched cells — chromatophores — which appear first in the outermost layer next the sclera and gradually spread inwards. The same type of branched pigment cells are found in the mesodermal layers of the ciliary region and iris. The development of pigment in the stroma of the iris appears after birth and to a very variable extent, being scanty in blue and grey eyes, but in brown eyes there is a thick deposit in the superficial layers which obscures the view of the vessels of the iris. In albinos pigment is diminished or absent in both the retinal epithelium and the mesodermal layers of the eye.

Fig. 51. — Section of the Retina of a 12-MM. Human Embryo. (R. J. G.) p.g. : pigment granules lying in the epithelium which forms the outer wall of the optic cup. ret. : retina. pi. ch. c. : plexus chorio-capillaris, containing vessels filled with erythro blasts. mes. : mesoderm.

The pigmentation of the lateral eyes in lower types of vertebrates does not vary in any essential manner from that in the human eye. In all cases, whether in the choroid or in the retina, we find the same kind of deep coloured pigment (melanin), which when viewed en masse in thick sections appears black. In making a comparison of this actively functional dark pigment in eyes which when in use are exposed to bright light with the pigment of the pineal body (basal epiphysis) which in the higher types of vertebrates is enclosed in the cranial cavity and is never exposed to light, one may note, as has been pointed out by Quast, that the pigment found in the parenchymal cells is of a yellow-brown colour and resembles the type of pigment which is found in degenerating nerve cells either in disease or in advanced age. Where the pigment is darker in colour, as in the membranes and in the supporting tissue, the explanation is probably to be found in the nature of the blood supply, which like that of the suprarenal body approaches the sinusoidal type. It may be assumed that owing to a slowing down of the circulation, any chromatophores or pigment-producing substances would tend to be deposited either in the meshes of the reticulum or in the substance of the cells. The deposit of dark pigment in the retina of the parietal organ is obviously an hereditary condition.

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Cite this page: Hill, M.A. (2024, April 26) Embryology Book - The Pineal Organ (1940) 3. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Book_-_The_Pineal_Organ_(1940)_3

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