Paper - The morphology, origin, and evolution of function of the pituitary body, and its relation to the central nervous system (1894)

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Andriezen WL. The morphology, origin, and evolution of function of the pituitary body, and its relation to the central nervous system. (1894) Br Med J. 1894 Jan 13; 1(1724): 54–58. PMCID: PMC2403749

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This historic 1894 paper by Andriezen describes the early understanding of pituitary development.

Links: 1908 Pituitary Histology | 1918 Rabbit Hypophysis | 1926 Human Hypophysis

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The Morphology, Origin, and Evolution of function of the Pituitary Body, and its relation to the Central Nervous System

By W. Lloyd Andriezen, M.D.Lonp.,

From the Pathological Laboratories of University College, London, and the West Riding Asylum, Wakefield.

  • Abstract of a paper read in the Section of Pathology at the Annual Mecting of the British Medical Association held at Newcastle, August 4th, 98 : . Jan. 13, 1894

The pituitary body occupies the position the pineal body once did. The latter was even suppposed to be the seat of the soul (Descartes), the pathway of a gullet (Owen, de Blainville), ete., till De Graaf and Spencer in 1886 showed its true significance.

My researches were commenced March, 1891. The material used was a large number of specimens, living and preserved, of larval and young amphioxus, larval and adult ascidians (oikopleura, salpa, pyrosoma), young and adult balanoglossus, ammoccetes and adult petromyzon, various fishes, and larval and adult amphibians. I have made further studies more recently on fcetal and young kittens. and the pituitary organs of the rabbit, rat, monkey, and man to elucidate points which arose from the work with the lower forms (see Zoological Tree, p. 55).

Authors who had hitherto studied the pituitary body began from myxine upwards, for example, Miiller, Virch. Arch., 1871, and others in his footsteps. Many clues were thus lost which only the investigation of the earliest, and especially acraniate vertebrates, could afford. Real lightis thrown only by the investigation of ammocctes (larval petromyzon) and lower forms, for these evidence a twofold function of the pituitary, and explein its twofold structure. for even in the highest mammals and man it has a twofold structure, and represents a double organ.

Zoological Tree (Phylogeny) of Vertebrata. a

\Mamunals \ Reptiles, Birds

Amphibia “ Fishes and Dipnot

Petromyzon CYCLOsSTOMA< Myzxine (Ammocetes)

« Larval

AMPHIOXUS ASCIDIANS; forms LL i t Saccata BALANOGLOSSUS | Nemertina ......... Ancestral wee Mollusca


My investigations in larval amphioxus showed that the‘ subneural gland” and its relations to the neural tube are of importance. This organ exists (a) in a position corresponding to the pituitary of higher animals, (4) presents the_ histological structure of a secretory gland, (c)is developed from buccal epiblast, and (d) has anatomical connections both with the brain floor and the buccal roof. It is obviously the homologue of the pituitary. To particularise: observations showed the development of a small and specialised group of nerve cells in the basal part of the brain cavity (thalamocoel) with which the subneural gland came into relationship. The central canai of the spinal cord, traced forward into this region, was seen to undergo dilatation into a distinct ventricle. “Adult forms do not exhibit this so well.) A duct was further formed, which had a capillary lumen lined by ciliated epithelium, and establishing a connection between the buccal cavity and the ‘‘ ventricular” cavity (thalamocoel). (It isnot to be confounded with Rathke’s diverticulum of the hypophysis, which can be seen in all embryonic mammals, includung man, aud is a blind tube denoting the tract of invagination and sinking of the hypophysis.) The nerve cells (before mentioned) aggregated around the neural opening of this duct into the neural tube; the epithelial cells (subneural gland) aggregated around the lower or buccal opening of the duct.

Owing to the degenerate character of amphioxus and its asymmetrical development in later larval life, certain alterations take place. These are to be looked upon as adaptive, and not genetic or fundamental; the notochord elongates anteriorly, the subneural gland, and oral cavity are displaced ilaterally ; even the myotomes get displaced, this last condition persisting to adult life (cf. similar adaptive asymmetrical «changes in flat fishes and molluses). The study of other allied forms enables us to ‘‘allow”’ for this disturbing factor.

The study of the larval ammoccetes affords a more distinct realisation of the conditions foreshadowed in larval amphi‘oxus, and one undisturbed by adaptive (or adventitious) asymmetry.

The pituitary in amphioxus and ammocoetes is a threefold structure, namely: (a) a subneural glandular organ, primarily median, and originating from the epithelium of the buccal roof at the orifice (J) of a duct lined by ciliated epithelium, which affords a communication between the buccal and neural.cavities, and (ec) a group of nerve cells around and at the back of the upper opening, where the duct widens into the -ventricular cavity. This widening part is the infundihulum, and the duct may be called the buccal infundibular

uct. It occurred to me that this duct would at once allow a current of water to enter the ventricle from the buccal cavity. To demonstrate it was the crucial point; by using a very fine emulsion of carmine suspended in the water in which these animals lived, and passing it towards them by a fine mozzle, a slow stream could be passed from the bottle containing the carmine emulsion. After an hour and a-half to ‘two hours, on killing the animal with OsO,, and observing it under the microscope, a number of fine carmine particles could be seen in the duct, and lining all over the ventricle.

By keeping the animils alive ‘onger exposed to the carmine stream, similar particles coull be traced step by step into the central canal of the cord; after a day along the whole length of the cord, and right up to the posterior free end of the canal, where the spinal canal opened into the exterior by the blastopore (neurenteric canal).

It was thus obvious that there was a 7aison d’étre for the buccal-ventricular duct where the stieam of water entered, for the ciliated epithelium of the central nervous cavities which propelled this stream, and for the neurenteric aperture? which formed the outlet for the exit of the water current after its passage through the central nervous system.

It was thus shown that the buccal-ventricular duct served as the inlet whereby a stream of oxygen-bearing water could enter the central nervous system ; and as the water (in which the animal lived) streamed slowly through the nervous tube by ciliary action, the nerve tissue would be enabled to take up oxygen from the water current, while the gaseous (CO,) and other products of the activity of the nerve tissue would similarly pass into and exit with the outflowing stream from the posterior (and still patent) end of the neural canal.

The duct portion of the pituitary was then the inlet of a water-vascular stream which brought in oxygen to the central nervous system, while similarly the neurenteric canal, which opened into the exterior posteriorly, served as the outlet to carry away the waste products by means of the outgoing water-vascular current in ancestral vertebrata.

A similar mechanism of a water-vascular current irrigating the nerve tissues is also found in a striking form in the nervous system of various larval and adult ascidians, in balanoglossus,* ammocoetes, etc., while in the phyla of the animal kingdom which approximate morphologically and genetically to ancestral vertebrata (namely, larval forms of mollusca and of echinoderma) water-vascular systems of a complex kind are found permeating the tissues and organs of the body generally—being a widespread biological phenomenon in ancestral vertebrata and their allies.

A complete zoological survey enables us to formulate facts in the following terms: that a water-vascular system permeating the body tissues, and serving for the in-bringing of oxygen, and the out-taking of waste products, and having inlets and outlets communicating with the aqueous medium in which the animal lives, preceded, in point of time, the development; and elaboration of a true blood-vascular system. .

Study of the degenerate ascidian Botryllus affords an instructive lesson. As the result of a fixed parasitic degenerate life, the olfactory organs and centre go, the visual organs and centre cease developing, and also atrophy. In the larva of botryllus the thalamocoel gets thickened in its basal part, where an aggregation of nerve cells can ‘be seen as in other forms mentioned. .

A tube is also formed connecting the stomodaeum with the thalamocoel (the buccal with the neural cavities). In the larval active form, the stream of oxygen thereby enters and aérates the brain; in the adult the fixed parasitic life demands neither brain nor body activity in the same degree ; and, in correlation with that, and, owing to adaptive modifications of the head region generally, the duct closes and is obliterated.

The buccal-ventricular duct is ventral to the anterior end of the central nervous system. Its pore isa ventral neuropore, which marked the communication between buccal and ventricular cavity, and the inlet of. the water-vascular current.

  • 2 The sesearches of Kowalevsky on Ascidians, of Gitte on Amphibia, of Kélliker, His, Balfour, all agree in showing the existence of a neuranal “ ihe larva of balanoglossus (tarnaria), and the bipinaria larva of asteroids (echinoderms) also show water-vascular organs, showing the extreme antiquity of this.system, andits deep significance in the animal lingdom.

An earlier condition of affairs, somewhat previous in point of time to the ventral neuropore and pituitary formations, was the formation of a dorsal neuropore, which, however, soon closed in amphioxus, though in ascidians and balanoglossus the dorsal neuropore persisted into adult life. In balanoglossus a dorsal neuropore is seen, in which the opening reaches the brain surface only ; in the more active young the brain is hollow, and its cavity (ventricular cavity) is in direct communication with the duct, which thus allows a stream of water (driven by ciliary action) to irrigate the brain tissue more intimately. In appendicularia and other larvalia, and in salpa (a free-swimming tunicate) a dorsal neuropore is present. In the young of salpa this ciliated tract or funnel opens into the brain cavity, though in the adult both brain cavity and ciliated tube get obliterated, and the brain becomes solid. The dorsal neuropore is also present in ammocoetes as a very transient phase. In higher forms rudiments of it (not functional) have been observed in elasmobranch fishes by Van Wijhe (1882), and by Kupfer in his monograph on Accipenser sturio (1893). It is also present in embryos of birds (Van Wijhe). lt is important to note that the dorsal neuropore or its vestige is anterior to the pineal body, which arises from the posterior edge of the roof of the thalamocoel), and dorsal in position to the olfactory centres (which arise in the anterior edge of the floor of the thalamocoel). The dorsal neuropore is a more archaic structure, and represents the region where the anterior dorsal end of the nerve tube failed to sink into the tissues deeply like the rest of the nervous system. The ventral pituitary duct (buccal-infundibular duct) was a later formation in the race, appears later in the individual, and achieved a higher grade in development, having associated with it the complex structure of the glandular pituitary (anterior lobe) and the nervous pituitary (posterior lobe of higher forms). This view is strikingly borne out by the recent investigation of Salensky on pyrosoma.* This organism presents two morphological types (zooids), namely, the cyathozooid (a sexually produced rudimentary zooid) and the aseidiozooid (a more mature budded-out form). The former piesents only the dorsal ciliated pit; the latter, which is more advanced, presents also the dorsal pit (at first), followed by the later and more developed ventral duct (pituitary duct) of stomodoeal origin. The obvious necessity of supplying a considerabie amount of oxygen to the central nervous tissues was thus realised, though imperfectly, in balanoglossus, salp2, appendicularia, and the two types of pyrosoma by the dorsal neuropore and its connections with the ventricular cavity dorsally. At a later stage and in the more highly-developed ascidizooid of pyrosoma, in salpa, in amphioxus, and in ammocoetes this was realised by the more complex duct and its associated organ, the pituitary, the further significance of which now remains to be seen.

These organs associated with the duct form, as mentioned before, are, (a2) aglandular secreting structure of buccal origin (epiblastic), and (5) a nervous centre developed at the base of the brain at the orifice where the duct lumen widened into the ventricular cavity. Such a nervous organ situated at the orifice whereby the stream of water enters the cavities of the central nervous system would be sensitive to the quality of the water which passes over it. This is no isolated phenomenon, for we finda striking analogy in the osphradial organ .and ganglion of mollusca, which is situated at the entry of the mantle or respiratory chamber and serves to test the quality of the water which passes over the respiratory organ. The obvious significance of the group of nerve cells which form the posterior lobe of the pituitary and are continued a little way up the infundibulum is that—namely, to be sensitive to the noxious quality or otherwise of the water which would enter and permeate the central nervous system. Similar specialised sensitive structures develop according to a well 2cognised biological law at other orifices (buccal, respiratory, generative, etc.). From this group of mainly fusiform nerve cells peripheral processes can be traced which run down to and end freely at the buccal orifice of the duct and in its lumen, and in the newborn and fetal kitten brain by the method of staining with chromate of silver, the central processes of these cells can be traced far backwards towards the pons. In ancestral vertebrate forms, where the pituitary duct was still functional and formed the inlet of the watervascular stream, the sensitive nerve centre at its orifice would also be functional, while later, with the advent and growth of a blood-vascular system permeating the central nervous organs, and thereby bringing oxygen to the nerve tissues, the necessity for a water-vascular current would no longer exist. The pituitary duct thus closed up and gets obliterated (by a growth of vessels, of connective tissue, and neuroglia). and the sensorv nervous structure in connection with it functions no longer and atrophies. All the above agree with facts of observation ; the posterior or nervous lobe of the pituitary begins to atrophy in all forms above larval petremyzon, and in the mammals and man is an exceedingly atrophied organ possessed of very little besides neuroglia.

The ensemble of evidence recorded tend to prove that the pituitary is not asimple structure having one simple funetion, of a complex organ composed of at least three parts, namely : (a) An anterior secreting glandular organ (of which more anon); (6) a water-vascular duct; (c)a posterior sensitive nervous lobe, of which the last two, namely, the duct and nervous lobe, were morphologically well developed and functioned in ancestral vertebrata, but have become obliterated and atrophied in structure and function for ever in al} forms above larval acraniates and ammocoetes. The posterior lobe begins to lose its nerve substance as we ascend the animal scale from ammocoetes upwards. In the larva of frog or salamander the progress of atrophy can be clearly recognised. Portions of the nervous infundibulum get thinned down here and there, in places being reduced to a mere thin layer of ependyma covered by a highly vascular pia, while the ingrowing loops of blood vessels push the ependyma in here and there towards the infundibular cavity, giving this part of the posterior lobe of the pituitary the appearance of a highly vascular plexiform saccular structure (saccus vasculosus of fishes and amphibia). Traced up to man, the posterior lobe represents little beyond a neuroglia remnant of what was once a functional portion of nerve tissue in ancestral verte rata.’

The glandular secreting portion (anterior lobe) of the pituitary is the type of a secreting structure of epithelial cells arranged in lobules and ascini, with many ducts opening into one main duct (the buccal-ventricular or pituitary duct). Histological examination of it in ammocoetes and young fishes shows it, and also shows its relation to the infundibulum and posterior lobe.

The minute structure and microchemical staining reactions all agree that the glandular epithelioma is secretory*; and in these early forms the secretion poured into the duct would be carried with the water-vascular stream through the central nervous system.

Such a phenomenon is significant. It cannot be that a definite glandular secreting organ, developed at the orifice of a definite tube, and having its secretion carried through the said tube and so through the central nervous organs, mixed up with the oxygen-bearing water, and therefore coming into intimate contact with the nerve tissues, is non-significant. It is of some use to the organism, and must especially be so in the economy of the metabolism of the nerve tissues, just as much as _the oxygen borne by the water current is. Its action would be one of two things, namely: (a) a trophic action on the nerve tissues, enabling them the more readily to take up and assimilate the oxygen of the water-vascular current; or (46) a destructive action, serving to neutralise and render innocuous the waste products of the activity of the said nerve tissues. Between two such alternatives it is difficult to decide, and after all it may be that at the root the two functions are intimately related; an adequate assimilation of the oxygen by the nerve tissues securing an adequate destruction (by oxidation) of the material products of nervous metabolism.’

We have seen how, with the development of the bloodvascular system invading the central nervous organs, and thereby bringing oxygen to the nerve tissues, the need for a water-vascular current no longer exists, and how the pituitary duct gets closed, the posterior neural canal (neurenteric canal) closes, the ciliated epithelium begins to show atrophy

5 The replacement of a water-vascular by a blood-vascular system in the animal kingdom, the obliteration of the water-vascular orifice and infundibular duct, the atrophy of the sensitive nervous structure connected therewith, the closing, similarly, of the outlet (neurenteric canal) of the water-vascular stream, and the final and gradual degeneration of the cilia in the central epithelium which formed the motive power which propelled the water current through the central nervous system—all seem an instructive lesson in evolution and dissolution.

6 See evidence collected by Boyce (Jour. of Pathol., 1892-98) and Beadles.

7 Thus Hoppe-Seyler has shown (Virchow’s Festschrift, 1891) that in the functional activity of cells the formation of lactic acid—a toxic metabolic by-product—is due to insufficient oxygen supply, and that if abundant O is supplied, the tissue takes it up and further oxidises the lactic acid into CO, and H.O, which ere eliminatel Other and similer examples

of the cilia, and the nervous tissue of the posterior lobe of the pituitary functions no longer, is not needed, and begins to die and dwindle away.

Is the secretion of the anterior glandular lobe needed after the closure of the pituitary duct and the cessation of the water-vascular stream which once carried it to the nerve tissues? Yes, for the oxygen is now brought to the nervous tissue by the blood-vascular stream. Hence the pituitary gland continues to produce its secretion, which, now that its duct is obliterated and the gland changed into a ductless gland, becomes an “internal secretion,” which, being absorbed by the lymphatics,? and therefore passing once more into the circulation, enters into the nerve tissues with the blood-vascular stream.

The fluid which was once passed as an ‘‘external secretion” with the water current which permeated the nervous system is now reabsorbed into the lymphatics, and goes with the general blood current once more tothe nerve tissues. It still acts on the nervous system; its old trophic function is not abolished under the new régime, but maintained. (In fact the activity of the gland would seem to be for a time at least increased, judging by the large relative size and great ee of the organ as we pass up from the cyclostoma


As we ascend the vertebrate scale still higher, through amphibia to mammals and man, its relative size does not keep pace with the increased growth of the nervous system-— an indication probably that, having attained the acme of its activity in lower vertebrates, it is in higher forms already beginning to show signs of diminishing activity, though, of course, still functionally active even in man.

In passing, a reference is needed to the views on the oral cavity as representing a pair of coalesced (right and left) gill slits, and that the hypophysis was the representative of a pair of preoral gill arches (Dohrn), which has been carried to an extreme by Marshall (1882). These views were partly the outcome of an erroneous interpretation of the value of branchiomerism in determining metameric segmentation of the head, and partly the outcome of a similar attempt to apply the ‘‘ vertebrate theory” of Goethe to the formation of the anterior head region (Goethe’s and Oken’s views, developed_by Owen). Both views have been shown to be unsupported by facts, and a more correct orientation of the head structures (both oral and preoral) have shown (Van Wijke, 1882; Ahlborn, 1884; Gegenbaur, 1887; Lankester, Rabl, Hatschek, 1888-92) that all gill arches and gill clefts are postoral, that analogous structures do not exist in oral or preoral regions, that branchiomerism is not parallel, and does not correspond with metamerism.

A survey and investigation based on all classes of vertebrata show that the hypophysis occupies the position and relationship to the other structures which may be condensed into the following table:

Relation of Pituitary to other Nerve Centres and Head Structure,

tn order from before back.

oo PS Olfactory centre. Posterior lobe of The bulbo-spinal os pituitary centres. 28 8 P Olfa: tory nerves. Hypophyseal Bulbo-spinal © nerves. nerves. a a8 Epithelium of | Pituitary ductand | Buccal, etc., and ez nasal sac. gland (anterior general cutaneous. Az lobe).

2 g a Pre-oral Oral. Post-oral O'S (prostomial). (branchial, etc., Ro and general body).

The old views of Blainville and Owen that the pituitary represents the pathway of an invertebrate gullet were based on erroneous interpretations of zoological facts; a revival of similar views—for example, in making the third ventricle represent a cephalic stomach as in crustacea, and the central canal of the cord the remnants of a pre-vertebrate gut (Gaskell

§ As proved by actual histological examination ; (Cf. thyroid) evidence tea) ated by Horsley, Boyce, etc. (Univ. Coll, hol. Lab. Reports,

and Bland Sutton)—has failed through want of adequate zoological, histological, or pathological evidence ; while, on the other hand, Hubrecht’s and Lankester’s view of the origin of vertebrates from platyhelmia, of which living nemertinae are the nearest allies, still remains established, in contrast to the others and further evidence is daily accumulating.

In regard to the size and weight of the pituitary, its prevalent variations—from 0.3 to 0.6 g. (Quain, 1881); and 0.4 to 0.9 g. (Boyce and Beadles, 1892)—would bring it under the Darwinian law of panmixia ; if so, the indication being what study of lower vertebrates shows, namely, that it has probably passed the acme of its activity, and in man is functioning less vigorously. .

reference is needed to the thyroid and its functions in lower vertebrata before concluding. The author has investigated this organ during the last year, and at the discussion three days ago (August Ist, 1893) on the function of the thyroid was able to state that the origin and mode of evolution and its activity in lower forms indicates that the thyroid is to be looked upon as associated anatomically with a primitive respiratory system, and physiologically with the respiratory gaseous exchange of the blood and tissues; while the phenomena following its destruction by disease or experiment are to be interpreted as at the bottom a disturbance of the gaseous metabolism‘ and malassimilation of oxygen by the body tissues, to which are probably correlated the subnormal temperature, weakness, twitchings, excess of fat, and languor and weakness of muscular and brain tissues consequent upon such destruction.

aving regard to the obvious features of parallelism which both organs, according to the author, thus exhibit in their early evolution in vertebrate animals, a physiological relationship would seem to exist between the thyroid and the pituitary glands. If such an explanation is correct, the recent results of enlargement (? compensatory) of the pituitary after thyroidectomy may be explained; for the concordant results of Stieda, Hofmeister, and Gley (1892-3), go to provesuch an enlargement of the pituitary after thyroidectomy.. But otherwise the parallelism fails, for the pituitary belongs Loth anatomically and physiologically to the central nervous system, and the thyroid to the respiratory function of the blood-vascular system, and thereby of the tissues. generally.

The main conclusions from the above lines of investigation all point to the important trophic influence of the pitui-tary gland on the central nervous system of vertebrates. If the origin and mode of evolution of its function be such, we ought clearly to get definite and predicable effects from theablation or destruction of the gland whether experimentally or by disease. The evidence of disease has not yet thrown. light on the nature of its function and experimental destruc-. tion (so far as the author is aware) has Fiven negative results. (Horsley, 1886; Gley, Marinesco, and others, 1892-3; and’ literature to end of March, 1893). Negative results are, however, of doubtful value, and cannot overweigh the positive: evidence derived from comparative study based on sufficiently extensive material, and where all the facts concerning origin and mode of evolution of both structure and function are harmonious and consistent. ‘The author there-fore ventures to state what such predicable effects might be in successful cases of ablation of the pituitary. For it was stated above as the result of the present investigation, that. the pituitary gland exercises a trophic action on the nerve tissues, which in more definite terms meant ‘enabling them. (a) to take up and assimilate oxygen from the blood stream, and (bd) to destroy and render innocuous the waste products: of metabolism, and that at root these two functions are intimately related, and are really at root part of one process (vital or bio-chemical) ; an adequate assimilation of oxygen by the nerve tissues securing an adequate destruction (by oxidation) of the waste products.” ®

The predicable results of the ablation or destruction of the gland would therefore be those due to (a) a malassimilation of oxygen by the nerve tissues, and simultaneously (6) an insufficient destruction, and therefore accumulation of waste products; thus bringing about a rapid nutritional failure and death of the central nervous system. In general terms we would therefore expect in the animal :

1. Depression and apathy (the commencing failure of activity in the nerve centres); and oO

2. Muscular weakness (the first peripheral effect).

3. Loss of fine co-ordination and equilibration (correlated to 1 and 2), and :

_4. The development of twitchings and irregular contractions (spasms) of the muscles (in relation to the furcher progress of nutritive failure of the nerve centres).

5. A want of sufficient heat production, and subnormal temperature.

6, A wasting of the body tissues (in relation to the more rapid failure of nutrition of the central nervous system). .

7. A probable compensatory polypnaa, or attacks of dyspncex (the peripheral] indication of the failure of the nerve centres to assimilate oxygen).

8. A rapid progress towards death. negative or confirm these statements.

In conclusion, the author would wish to call attention to the undoubted value of studying biological problems (to the physiologist and pathologist) from the comparative and zoological standpoints, and by experiments on the lower vertebrates, to obtain light more particularly .on the origin and evolutions of structures and functions and to, understand their raison @étre in relation to the higher animals and:man, following especially uhe method of the great Darwin.’°

Future research must