Book - The brain of the tiger salamander 8

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Herrick CJ. The Brain of the Tiger Salamander (1948) The University Of Chicago Press, Chicago, Illinois.

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Pages where the terms "Historic" (textbooks, papers, people, recommendations) appear on this site, and sections within pages where this disclaimer appears, indicate that the content and scientific understanding are specific to the time of publication. This means that while some scientific descriptions are still accurate, the terminology and interpretation of the developmental mechanisms reflect the understanding at the time of original publication and those of the preceding periods, these terms, interpretations and recommendations may not reflect our current scientific understanding.     (More? Embryology History | Historic Embryology Papers)

Part I. General Description and Interpretation 1. Salamander Brains | 2. Form and Brain Subdivisions | 3. Histological Structure | 4. Regional Analysis | 5. Functional Analysis, Central and Peripheral | 6. Physiological Interpretations | VII. The Origin and Significance of Cerebral Cortex | VIII. General Principles of Morphogenesis Part 2. Survey of Internal Structure 9. Spinal Cord and Bulbo-spinal Junction | 10. Cranial Nerves | 11. Medulla Oblongata | 12. Cerebellum | 13. Isthmus | 14. Interpeduncular Nucleus | 15. Midbrain | 16. Optic and Visual-motor Systems | 17. Diencephalon | 18. Habenula and Connections | 19. Cerebral Hemispheres | 20. Systems of Fibers | 21. Commissures | Bibliography | Illustrations | salamander

Chapter VIII General Principles of Morphogenesis

Throughout the preceding descriptions and interpretations, some general morphological principles are implicit. Since these are moot questions, it is fitting that these assumptions be explicitly stated and clarified. Several years ago in a discussion of the morphogenesis of the brain ('33a) , some of these principles were critically examined, and a part of what follows is condensed from that essay.

Morphogenic Agencies

A century and a half ago the German Naturphilosophie elaborated the mystic and poetic conception of an archetypical form, which was popularized by Oken and Goethe and culminated with Sir Richard Owen and Louis Agassiz. As Professor Owen wrote in 1849: "The archetypal idea was manifested in the flesh under diverse such modifications, upon this planet, long prior to the existence of those animal species that actually exemplify it." These geistige Krcifte were conceived as enduring morphogenic agencies which shape the course of all animal and plant differentiation.

After the publication of Darwin's Origin of Species in 1859, a new school of morphologists arose under the leadership of men like Gegenbaur, Haeckel, and T. H. Huxley, the guiding principle being a search for phylogenetic relationships as key factors in morphogenesis. The mystic enduement of the earlier archetype was replaced by a sound biological principle of progressive change effected by verifiable internal and environmental agencies.

This conception of morphology as the visible record of phylogenetic history has stood the test of time. It is dynamic, not static; and our search is for the natural agencies which have operated to produce the observed modifications of form and correlated behavior during the course of evolutionary change. This century of progress has, however, witnessed a curious relapse, with resurgence of the ancient predilection for rigid categories and artificial systems of logical analysis, which yield in the end a formulation of inflexible, and therefore obstructive, morphological principles. Ancient and heritable patterns, such as metamerism, germ layers, and so on, were formalized, and the tendency was to regard them as stable and immutable factors in morphogenesis. The problems were thus simplified in terms of misleading logical categories, resulting in a static, rather than a dynamic, analysis of development and evolution. These formal and rigid concepts have too often retarded, rather than facilitated, a true understanding of the structure.

The dialectic of some current "form-analytic" programs of research on morphogenesis of the brain seems to postulate a predetermined primordial pattern of the neural tube, which is preserved throughout all stages of differentiation and which can be recognized by the arrangement in space of cellular areas and their relations to one another independently of their functional connections or of any dynamic agencies in morphogenesis other than cellular proliferation. The result is an oversimplified, logically consistent, morphological schema uncontaminated by functional or other complicating factors; but this has little interest for the working anatomists and physiologists, for it has no obvious relation with the structural forms with which they are practically working. Nerve fibers are quite as important as cell bodies in cerebral organization and as elements in cerebral forms. By what right does the morphologist ignore them in his study of form? We have ample evidence that the growth of nerve fibers and the migration of cells may be determined by functional requirements, which differ from species to species in correlation with different modes of life. Are forms which have physiological meaning of no significance in morphology, and can they safely be ignored by morphology.^

My paper of 1933 cites several illustrations from my own experience and that of others of the seductive influence of rigid categories of morphological concepts, which simplify analysis by neglect of other significant factors in morphogenesis. In modern morphology the search is for genetic relationships, and homologies are defined in terms of such relations. In all phylogenetic study we must constantly keep in the foreground of attention two main classes of morphogenetic agencies. These are, first, the conservative factor of stable genetic organization and, second, the more labile influence of the specific functional requirements. Both factors are always present, and one important task of the morphologist is the analysis of his material so as to reveal the parts played by each of them. A sound and fruitful morphology will take both into account. For the practical purposes of descriptive anatomy and experimental physiology an analysis in terms of functional efficiency is indispensable, and a morphology which ignores the dynamic factors of tissue differentiation in terms of physiological adaptiveness lacks something and is sterile, as I have repeatedly emphasized ('08, '10, '13, '226, '25a, '33a).

This does not imply that in either embryonic or phylogenetic development the pattern of structural differentiation is determined primarily by peripheral influences, which, acting directly on the germplasm, produce heritable changes in its structure. Whether such inheritance of acquired characters ever occurs is in controversy. Certainly it is the general rule that adaptation of structure to physiological requirements is effected by indirection — natural selection or some other principle — but that it is acquired in some way is evident, and these physiological requirements are key factors in morphogenesis. This is more evident in the nervous system, perhaps, than in other organs of the body, for one of the prime functions of nervous tissue is adjustment of the body to its environment.

The analysis of morphogenic factors is best accomplished experimentally, as is well illustrated by Holtfreter's recent study ('45). This paper sets out in sharp relief the contrast between growth and differentiation. The relation between intrinsic and extrinsic factors and between nuclear and cytoplasmic influences in morphogenesis is discussed in two recent books by W. E. Agar ('43, chap, v) and R. S. Lillie ('45, chap. x). The reciprocal relations between genes and cytoplasm are now under active investigation.

There is decisive evidence that in embryogenesis the pattern of differentiation of both sensory and motor systems is determined largely by intrinsic agencies and that it proceeds more or less autonomously up to functional capacity. These structural patterns are laid down in the inherited organization, and that organization has been elaborated in the course of phylogenetic development in adaptation to the physiological needs. of the species in question. Morphology here ties in with ecology.

The last point carries with it the necessary implication that the intrinsic agencies which initiate and shape the course of embryonic differentiation are not strictly autonomous and that even the hereditary factors have arisen ab initio as responses of the protoplasmic organization to environmental influences. It is this point of view which has been emphasized by Child ('41) in his search for more general morphogenic agencies which antedate the speciaHzed features of ontogenetic differentiation. The old controversies about preformation versus epigenesis are outmoded and may well be ignored, for both factors are present in all development. It can no longer be claimed that "the basis of developmental pattern is an inherent property of protoplasm and therefore continuously present and independent of external conditions" (Child, p. 6), for at no period in the life of any organism is it independent of its environment. The vital process is fundamentally an interaction between the protoplasmic organization and its surroundings— respiration, nutrition, and all the rest. But when a given heritable pattern of internal organization has once been established, then the several components of this organization may acquire a large measure of autonomy in both further development and adult function. This specialization has obviously taken place; and when, in the course of development of vertebrate neuromuscular organs, they are approaching functional capacity, the patterns of this performance, though not independent of internal and external environment, clearly are not directly determined by any specific influences acting upon them from receptor organs. In this restricted sense these patterns are initiated intrinsically, and their performance is autonomous. But throughout development there is a complicated interaction of the inherited factors with one another, and this intrinsic interplay of moiphogenic agencies is an important feature of developmental mechanics.

The widely current belief that heritable variations sometimes occur in progressive series set in a definite direction rather than always in accordance with the probability curve of chance deviations around fixed unit characters has been strongly supported by many independent lines of evidence. It has been pointed out that the progressive senescence of tissue in both ontogenetic and phylogenetic series involves a fixation or stabilization of originally undifferentiated plastic tissue into permanent structural patterns. So far as this differentiation is heritable and irreversible, the future course of evolution is thereby intrinsically determined, for variations will be distributed around the new pattern as a mode in accordance with a different frequency curve than would be shown if the inherited structural pattern were different. The process of differentiation is therefore itself a natural cause of limitation of the future course of evolution within boundaries set by the efficient working of the established pattern. The nervous systems of arthropods, teleosts, reptiles, birds, and mammals furnish illustrations of the effect of such irreversible differentiation on the course of animal evolution. The significance of this principle in the evolution of the nervous system was briefly discussed in my paper on orthogenesis in liHO, and more fully subsequently ('21, '22a, '24c, '26, '33rt, '48).

In the embryo, as soon as connection is made between the sensory zone and the motor zone in the central nervous system, specific peripheral influences begin to operate to a much greater degree, and these may modify the subsequent course of development of the already fabricated sensory and motor apparatus and "inflect" the pattern of performance. The nature and degree of this modification by use is, however, limited to the range permitted by the pre-existing intrinsic organization (Coghill, '29, p. 86; Weiss, '41, p. 59). That this range is very restricted in the Amphibia has been made clear by much recent experimental work. The intrinsic growth factors which predetermine appropriate patterns of nervous organization in embryological development are operative also in the regeneration of peripheral nerves in the adult animal (see the experiments of Sperry cited on p. 228).

With progressive increase in the complexity of adjustment to the external and internal environment, there has been a corresponding differentiation of structure. The genetic organization determines the primary pattern, and this pattern is modified by use and the personal experience of the individual. The first of these factors yields that stable organization of tissue which is common to all members of the species and which forms the subject matter of most of the literature of neuroanatomy. The structural changes effected during growth by the second factor are harder to recognize, and this critical field is largely unexplored. In our examination of Ambly stoma we are searching for primordia of both these kinds of tissue — the stable heritable structure and the more labile, individually modifiable tissue involved in conditioning of reflexes and other adjustments to personal experience. Both components are at a low level of differentiation in this animal, but their characteristic structure is recognizable, and the successive steps of their further evolutionary development can be followed.

Most species of urodeles apparently are reversals from more highly differentiated ancestral forms. This, however, in its main features is not a dedifferentiation but an arrest of development, so that adult characteristics of the descendants resemble larval features of their ancestors. Such reversals and the accompanying instances of actual degeneration doubtless are brought into being by changes in the mechanism of heredity, involving rearrangement of the complicated pattern of the genes (Emerson, '42, '45). Evolution is an irreversible process, with divergent ramifications in inconceivable variety and many instances of approximate parallelism. The apparent repetitions, when viewed in time, are not circular but spiral in form; and apparent retrogressions are never exact reversals of the preceding historical sequence. When a mammal returns to the water, it does not become a fish. The amphibians present conspicuous illustrations of recapitulation in individual development of some features of the phylogenetic history, and most of the apparent retrogression is really an arrest of development, which does not go back so far as the piscine ancestry. Their limbs are not fins, and their gills are not fishlike. There is another functional factor in morphogenesis to which too little attention has been given— a greater or less capacity for socalled "spontaneous" activity, that is, behavior initiated internally and manifested in patterns determined by the intrinsic structure. All protoplasm is active as long as it is alive, and the essential vital properties are inherent in protoplasmic organization. This behavior is not a mere reflection of external influences, for the living stuff transforms the energies which impinge upon it and recombines them in original designs. Reserves are accumulated, and these are expendable on occasion in accordance with need, with or without external excitation. In the central nervous system this intrinsic "spontaneous" automaticity attains maximum potency, and it is exhibited by even isolated fragments of it in characteristic patterns, of which oscillographic records can be made. In the intact brain the interplay of these intrinsic activities is always going on, and as we pass from lower to higher animal types it becomes progressively a more and more important factor in determining patterns of behavior. The enormous reserves of potential nervous energy in the brain are evoked and manifested as stabilizing influences (cerebellum, corpus striatum, etc.) and also in that spontaneity, initiative, and inventiveness which culminate in cortically directed human behavior. These capacities are shown in some measure by all animals, and a search for the apparatus employed in even so lowly a creature as a salamander may be fruitful (see '48, chap, xv, for discussion of Coghill's contributions on automatism, spontaneity, and motivation).

It has been pointed out by von Bonin ('45) that the logical foundations of the concept of morphology based on phylogenesis as developed by T. H. Huxley, Gegenbaur, and others of their time are insecure. The mathematical argument need not here be examined, for it is based on certain restricted postulates, and in animal evolution there are many variables not embraced by these postulates. It certainly does not follow that "the task of understanding structures on the basis of their phylogenetic history" is "an insoluble problem." Though neither cultural history nor phylogenetic history has been reduced to mathematical formulation, there is general agreement that history, judiciously interpreted, is an accredited guide for understanding the present and prognosticating the future. Phylogenetic history is not a sealed book, and Dr. von Bonin assures me that he would be the last to deny a positive value to the historical approach to problems of morphogenesis and that such studies have actually contributed much toward an understanding of human cerebral structure and function. The positive paleontological evidence regarding the phylogeny of the brain is more extensive and illuminating than is generally recognized. Though fossilized brains are unknown, the very large number of casts of skull cavities, when skilfully interpreted, yield a surprising amount of reliable information about the nervous organs which once occupied those cavities, as illustrated, for instance, by Stensio's studies ('27) of fossil ostracoderms. It must be freely granted, of course, that conclusions reached are tentative, to be accepted only as checked against other lines of evidence, particularly the known sequence of evolutionary history as revealed by fossilized skeletal remains.

No single mode of attack upon problems of morphogenesis is adequate. Experimental methods yield the most decisive evidence, and these require adequate knowledge of anatomical structure. This last is the contribution of comparative anatomy and comparative embryology, and both of these must be functionally interpreted to be fruitful. The anatomist should recognize the limitations of his method. His task is to lay foundations — stable and adequately broad — and to suggest fruitful working hypotheses. The Amphibia occupy a strategic position here for the same reason that the experimentalists find them so useful.

Morphological Landmarks

Comparative study shows that some general features of structural plan run through the vertebrate series with remarkable constancy and that other features undergo amazing transformations. The discovery of the laws in accordance with which these transformations are effected is the goal toward which we are working. We are confronted with a similar, but not parallel, series of problems in the study of embryological development. In so far as we succeed in our search for these laws, we advance our understanding of fundamental vital processes.

The stable structural features of the nervous system are the most useful landmarks for the comparative anatomist. They are expressions of the conservative hereditary factor in morphogenesis ; but this stability cannot safely be interpreted as the simple manifestation of some primordial archetypical pattern, for these features are retained during the course of phylogenetic history only in so far as the fundamental features of the peripheral connections and their internal relationships are constant, that is, because they are parts of an apparatus of adjustment to environment which is common to all vertebrates. Other parts of the brain are more variable because, with complication of the behavior pattern in higher species, more elaborate and diversified mechanisms of adjustment and integration are requisite.

In all vertebrate brains the most fundamental structural landmark is the transverse plane separating the spinal cord and rhombencephalon below from the cerebrum (as defined in the BNA) above. In Amblystoma this plane is marked externally by the fissura isthmi and internally by the sulcus isthmi. The zonal arrangement as described in chapter v is well defined in the rhombic brain and the midbrain, rostrally of which it is obscured by various secondary modifications which become more complicated as we pass from lower to higher members of the vertebrate series. A second important landmark is the transverse plane separating the diencephalon from the telencephalon, marked externally by the deep stem-hemisphere fissure.

These two planes also mark the positions of two strong flexures of the neural tube in early embryonic stages, caused by inequalities of growth of the dorsal and ventral zones of the neural tube. The first of these flexures to appear is a ventral bending of the neural tube in the mesencephalic region, caused by precocious enlargement of the tectum. This is followed by a flexure in the reverse direction at the di-telencephalic junction (p. 212). These flexures are less obvious in adult brains because they are somewhat straightened in later stages and masked by growth of interstitial tissues; but the site of each of them is a zone of transition between major divisions of the brain with distinctive physiological characteristics.

The foundations of the current anatomical analysis of the brain were laid by Wilhelm His in terms of human embryological development. The early neural tube was divided into a linear series of blocks separated by transverse planes, and a longitudinal sulcus limitans on each side marks the boundary between a dorsal sensory alar plate and a ventral motor basal plate. The adult derivatives of this embryonic mosaic are the primary anatomical units. The nomenclature derived from this analysis as officially adopted (the BNA), or modifications of it, is now almost universally employed, to the great advantage of human descriptive neurology. But this scheme has its limitations. Some features of it are quite inapplicable to the brains of lower vertebrates; for, though the embryonic neural tube is similar in most of them, its adult derivatives vary so widely in adaptation to diverse modes of life that no inflexible formula is applicable. Since the brain of Amblystoma is generalized, few of these difficulties arise here.

There is difference of opinion about where the sulcus limitans ends anteriorly. If the embryonic floor plate ends at the fovea isthmi (Kingsbury, '30), it is evident that the basal plate extends farther forward to include the mesencephalic cerebral peduncle and probably more or less of the adjoining parts of the hypothalamus and ventral thalamus. The remainder of the mesencephalon and diencephalon (including the retina) and the whole of the telencephalon are derived from the expanded anterior part of the alar plate and the related neural crest. The adult derivatives of alar and basal plates include much tissue that is specifically neither sensory nor motor; and this intercalated associational fabric crosses the boundaries of the primitive embryonic mosaic in ways which difi^er from species to species. Each species must be analyzed in terms of its own mode of life and distinctive action system.

C. von Kupffer ('06) put special emphasis upon two deep transverse sulci in the ventricular wall of the neural tube in early embryonic stages of a series of lower vertebrates, including Necturus and Salamandra. These were termed sulcus intraencephalicus anterior and posterior. Study of later stages of developing urodele brains shows that this emphasis was well placed, for these sulci mark the positions of the two transitional sectors of the brain to which reference was made above — the first, the diencephalic, and the second, the isthmic sector.

In our specimens of Amblystoma, von Kupffer's anterior sulcus in early motile stages (Harrison's stages 33-36) is a sharply defined groove, which extends dorsally from the lateral optic recess in front of the chiasma ridge to the region of the velum transversum. Its dorsal part is varikble, but clearly the primary course is into the posterodorsal initial evagination of the hemispheric vesicle, as described b.y von Kupffer and by Rudebeck ('45). This is clearly the case also in A. jeffersonianum, as shown by Baker and Graves ('32) in their five stages from 5 to 17 mm. long. My published references to this sulcus and its adult derivatives have been successively modified, as more material was examined ('10, pp. -119, 43:2; '£7, p. 238; '33b, p. 240; '35a, p. 252; "38, p. 212; '38b, pp. 401, 402; '39a, p. 262). These differences in interpretation are doubtless due in part to the natural variability of the specimens and in part to lack of a sufficiently close series of well-preserved stages to reveal the actual sequence of the changes. In our Amblystoma material the ventral part of this sulcus seems to shift its position and to be transformed directly into the sulcus preopticus, and it was so described ('39a, p. 262). Rudebeck finds in dipnoans, Necturus, and Triturus that the sulcus intraencephalicus anterior passes from the lateral optic recess dorsalward to the posterodorsal hemispheric ventricle and that the definitive sulcus preopticus arises as a secondary outgrowth from this primary groove. Our specimens of Amblystoma have not revealed this secondary origin of the sulcus preopticus but resemble that of the anuran, Pelobates, as described by Rudebeck ('45, p. 53).

In Amblystoma the posterior intraencephalic sulcus of von Kupffer persists as the sulcus isthmi of the adult. In the 6-mm. Ammocoetes (von KupflFer's fig. 47) it extends transversely from the plica rhombo-mesencephalica to a point in the floor a short distance spinalward of the tuberculum posterius, i.e., to the fovea isthmi, and it is similar in several other species figured. During larval development of x\mblystoma it and the related external fissura isthmi shift their relative positions (p. 179). As emphasized above, this plane of separation between cerebrum and rhombencephalon, whether or not it is marked by a visible sulcus in the adult brain, in all vertebrates is the boundary between the two chief subdivisions of the brain.

The distinction between these subdivisions is conspicuous in prefunctional and early functional stages. Coghill ('24, Paper IV, p. 97; '31, Paper X, p. 162) reports that at all stages of development of Amblystoma from premotile to swimming the rate of proliferation of cells and differentiation of neuroblasts is rapid in rhombencephalon and spinal cord, on the one hand, and in the cerebrum, on the other hand; but "there is a distinct gap between fields of both differentiation and proliferation at the isthmus. Such a gap does not appear at any other level in the brain or cord." Diencephalon and telencephalon appear to be about equally involved in this process, and so do rhombencephalon and cord; but during these stages growth appears to be initiated independently in these two major divisions of the nervous system.

The experiments of Detwiler ('45, '46), to which reference has already been made (p. 62), show that ablation of the cerebral hemispheres and visual organs of Amblystoma in prefunctional stages results in no demonstrable change in size or weight of the medulla oblongata. He finds no evidence that the hemispheres or visual organs exert any morphogenic influence upon the medulla oblongata up to a larval age of 48 days (33 mm. in length), and these mutilated larvae are capable of performing all the ordinary feeding reactions.

The most primitive and fundamental patterns of total behavior are organized in the spinal cord and lower medulla oblongata, particularly at the bulbo-spinal junction. Very early these come under the control of the vestibular apparatus (Coghill, '30, p. 638) and midbrain, and this control must be maintained throughout life if the primitive mass movements are to retain their efficiency (Detwiler, '45; '46). The isthmus, interpolated between these regions, seems to be concerned mainly with the organization and control of local reflexes (partial patterns) of the medulla oblongata under the influence of both ascending and descending systems of correlation fibers.

For convenience of description the rhombic h^-ain is here arbitrarily divided into four regions, each with characteristic structure and functions: (1) the bulbo-spinal junction, (2) medulla oblongata, (3) cerebellum, (4) isthmus. In these regions the functionally defined zones are unevenly differentiated, and the cerebellum as a "suprasegmental" apparatus is in process of emergence from the sensoiy and intermediate zones. Similarly, in the forebrain the pallial field exhibits an early prodromal phase leading toward cortical differentiation, as seen in reptiles.

The rhombic brain receives all sensory components of the cranial nerves except the olfactory and the optic. In lower vertebrates, in which the auditory apparatus is at a very low level of differentiation, the sensory components of the rhombic nerves are relatively unspecialized, in sharp contrast with the highly specific optic and olfactory systems; and the physiological dominance of the two systems last mentioned in the control of behavior is the determining factor which gives to the cerebrum unique properties that are in marked contrast with those of the rhombencephalon.

The isthmus is a transitional sector, within which the patterns of all bulbar activities are ordered and integrated. It bulks larger in lower vertebrates than in higher, in which the cerebral cortex has taken over the larger part of this control. Above it the cerebellum was differentiated, not as part of the apparatus which patterns performance but as an ancillary mechanism on the efferent side of the arc, to reinforce and regulate the execution of movements.

Within the cerebrum the two primary centers of dominance — optic and olfactory — are separated by a similar transitional sector in the diencephalon. This is plastic tissue, not dominated by any single sensori-motor system; it is the meeting place of ascending and descending sensory paths. In noncorticated vertebrates we find here the apparatus of a type of adjustment from which influences pass forward into the hemispheres and there act as morphogenic agencies in the elaboration of cortical structure.

It appears, then, that the loci of some characteristic features of the vertebrate brain were fixed by their peripheral connections in the earliest members of the series and that some of these have remained essentially unchanged throughout the phylogenetic history. Others have emerged very gradually from a nonspecific matrix which is diffusely spread throughout a wide field. The search for primordia of the latter type in the lower forms as parts of a mosaic pattern with rigidly defined boundaries cannot be successful. In each animal species the tissue requisite for successful adjustment to the mode of life adopted is fabricated out of such raw material as is available, and nature is not bound by our formal rules of logical consistency. The major subdivisions of the brain were thus defined very early in vertebrate phylogeny, and they retain their general characteristics throughout the series, but there is no apparent limit to the range of modifications which these sectors may undergo in adaptation to specific physiological requirements.

In premotile stages of Amblystoma, Coghill mapped several areas in the walls of the neural tube, characterized by distinctive proliferation and differentiation. Adopting a modification of his scheme, I gave arbitrary numbers to twenty-two such areas from the olfactory bulb to the cerebellum ('37, p. 392), and their development can be followed up to the adult stage. These units of the mosaic pattern of the premotile embryo undergo remarkable shiftings of position during larval development and an equally remarkable diversity in patterns of differentiation and fibrous connections. When the comparative embryologist surveys the vertebrate series as a whole, he recognizes a striking similarity in the early stages of differentiation of the neural tube of all of them. In later stages of development this similarity gives way to wide diversity in the progress of differentiation of these primordial units of structure, and practically all this divergent specialization can be seen to be directed toward adaptive modifications of structure, correlated with differences in the action systems of the several species. Some limits to the range of this modifiability are set by the inherent qualities of the genetic organization so that some general principles of morphological pattern can be recognized everywhere. Yet the structure when viewed phylogenetically is remarkably plastic, and the available materials are adapted to a wide variety of uses in diverse combinations and interconnections in all the different phyla. The most alluring feature of these comparative studies lies in our ability to sort out of this apparent confusion of detail those strong threads of ancestral influence which are interwoven in ever changing designs under the influence of adaptive adjustment to different modes of life.

The Future Of Morphology

During the past half -century, morphology has seemed to be declining in favor, its problems submerged in the more attractive programs of the experimentalists. Nevertheless, activity in this field has not abated, and now there is a renaissance, the reasons for which are plain. Conventional methods of anatomical research have laid a secure factual foundation, but the superstructure must be designed on radically different lines. Several centuries of diligent inquiry by numerous competent workers have produced a vast amount of published research on the anatomy and physiology of the nervous systems of lower vertebrates; but most of this literature is meaningless to the student of the human nervous system, and, as mentioned at the beginning of this book, its significance for human neurology has until recently seemed hardly commensurate with the great labor expended upon it. The last two decades have inaugurated a radical change, in which we recognize two factors.

In the first place, technical improvements in the instrumentation and methods of attack have opened new fields of inquiry hitherto inaccessible. To cite only a few illustrations, new methods for the study of microchemistry and the physical chemistry of living substance, radical improvement in the optical efficiency of the compound microscope, the invention of the electron microscope, and the application of the oscillograph to the study of the electrophysiology of nervous tissue are opening new vistas in neurology, which involve quite as radical a revolution as that experienced a few centuries earlier when microscopy was first employed in biological research.

A second and even more significant revolution is in process in the mental attitudes of the workers themselves toward their problems and toward one another. A healthy skepticism regarding all traditional dogmas is liberating our minds and encouraging radical innovations in both methodology and interpretation. And, perhaps as a result of this, the traditional isolationism and compartition of the several academic disciplines is breaking down. The specialists are now converging their efforts upon the same workbench, and cooperative research by anatomists, physiologists, chemists, psychologists, clinical neurologists, psychiatrists, and pathologists yields results hitherto unattainable. What is actually going on in the brain during normal and disordered activity is slowly coming to light.

Here the comparative method comes to full fruition, and comparative morphology acquires meaning, not as an esoteric discipline dealing with abstractions but as an integral and indispensable component of the primary task of science — to understand nature and its processes and to learn how to adjust our own lives in harmony with natural things and events, including our own and our neighbors' motivations and satisfactions.

The objective toward which we are directing our efforts is a better understanding of human hfe and its instrumentation. Our mode of hfe has been achieved througli eons of evolutionary change, during which the conservative and rehitively stable organization of the brain stem has been supplemented and amplified by the addition of cortical apparatus with more labile patterns of action, resulting in greater freedom of adjustment to the exigencies of life. In all behavior there is a substrate of innate patterns of great antiquity, and in practical adjustments these primitive factors are manipulated and recombined in terms of the individual's personal experience. Memory and learning are pre-eminently cortical functions, but these cortical capacities have not been given to us by magic, and we want to know how they have been developed and the roots from which they have grown.

The incentives which motivate research in comparative neurology are the same as those of all other science, pure and applied, and of all truly humanistic endeavor in other fields— to find out what is good for humanity and how to get it. This implies, as I have recently exhorted ('44), that the humanistic values of science must always be acknowledged and cultivated.