WILLIAM €M€RSON RITTGR BOOKS BY WILLIAM EMERSON HITTER THE HIGHER USEFULNESS OF SCIENCE. THE PROBABLE INFINITY OF NATURE AND LIFE. THE UNITY OF THE ORGANISM, OR THE ORGANISMAL CONCEPTION OF LIFE. Illustrated. THE UNITY OF THE ORGANIC SPECIES, WITH SPECIAL REFERENCE TO THE HUMAN SPECIES. WAR, SCIENCE AND CIVILIZATION. AN ORGANISMAL CONCEPTION OF CONSCIOUSNESS. RICHARD G. BADGER, PUBLISHER, BOSTON FIGURE 56. SKELETOX OF PYTHOX. THE UNITY OF THE ORGANISM OR THE ORGANISMAL CONCEPTION OF LIFE BY WILLIAM EMERSON RITTER Director of the Scripps Institution for Biological Research of the University of California, La Jolla California TWO VOLUMES VOLUME TWO ILLUSTRATED BOSTON RICHARD G. BADGER THE GORHAM PRESS COPYRIGHT, 1919, BY RICHARD G. BADGER All Rights Reserved This work contains the text of the book: 'An Organismal Theory of Consciousness.' Made in the United States of America The Gorham Press, Boston, U. S. A. CONTENTS PART I CRITIQUE OF THE ELEMENTALIST CONCEPTION OF THE ORGANISM B. The Production of Individuals by Other Indiridiuils (Concluded) CHAPTER PAGE XIV. EVIDENCE FROM METAZOAN GERM-CELLS THAT SUBSTANCES OTHER THAN CHROMATIN ARE THE PHYSICAL BASES OF HEREDITY .......... 1 Evidence from spermatozoa, 1. Spermatozoa subject to heredity as well as "bearers of heredity," 1: (a) Illus- trated by the ontogeny of mammalian sperm, 4; (k) Illus- trated by the ontogeny of an insect sperm, 9. Evidence from the ovum, 15: (a) eggs of ascidians — the facts, 16; (6) Conklin's interpretation, 19. Critical examination of Conk- lin's interpretation, 23. XV. EVIDENCE FROM SOMATIC HISTOGENESIS IN THE MULTICELLULAR ORGANISMS 32 The mitochondrial theory of heredity, 32. The mitochon- dria! theory tested by the ontogeny of spermatozoa, 36. The mitochondrial theory tested by histogenesis, 37. The un- tenable hypothesis that cytoplasm of the ovum is inheritance material for general but not for special characters, 40. Spe- cies attributes in single cells of adult organisms, 43- The spinules of the ascidian genus styela, 44- The spicules of sponges and other invertebrates, 50. The '"hairs" of higher plants, 55. Cell-wall structures in higher plants, 57. The morphology of striated muscle fibers, 60. The physiology of muscle fibers, 61. Summary of positive information about the physical basis of heredity, 64. XVI. THE INHERITANCE MATERIALS OF GERM-CELLS INITIATORS RATHER THAN DETERMINERS ...... 66 Antecedents of the cytoplasmic and nuclear theories of in- ix x Contents M. \PTER PAGE heritance material, ('>(]. Function of chromosomes in heredity acquired and secondary, 67. The tiro-fold character of the problem of hereditary substance, 70. The probability that inheritance material becomes snch in each ontogeny, 73. Germ-cells subject to metabolism like all other cells, 74. Chemical changes in germ-cells during parent's ontogeny, 75. The possibility of changing sex by influences on the germ, 70. The determiner conception contrary to ordinary chem- ical principles, 79. Endorsement of E. B. Wilson's proposal to drop "determiner" from the vocabulary of genetics, 82. Advantages in conceiving germ-cell chromosomes as initia- tors in hereditary development, 83. Inconclusiveness of the cy to-logical evidence usually appealed to in support of the chromosome theory, Xj. Humming up of the findings against the chromosome theory, 87. Brief reference to the untoward implications of the germ-plasm conception of heredity, 89. PART II. THE CONSTRUCTIVE SIDE OF THE ORGANISMAL CONCEPTION XVII. GROWTH INTEGRATION ........ 93 The field to be covered by the constructive discussion, 93. Four types of bio-integration to be treated, 9^. Graded repetitive series as integrative phenomena, 95. Illustrations from, animals, 95. Illustrations from plants, 99. Justifica- tion for bringing all these phenomena under one head^ 103. Attempted casual explanation of these series, 104. Asial metabolic gradients as integrative phenomena, 107. M eristic gradients and metabolic gradients both phenomena of growth integration, 111. - XVIII. ClIEMICO-FUNCTIONAL INTEGRATION ..... 113 Functional as contrasted with growth integration, 113. The conception of "internal secretions," ll//. Effects of removing the human thyroid for curative purposes, 115. Experimental thyroid excision in normal lower animals, 117. The internal secretion of the duodenal mucous membrane, 119. The na- ture of the active substances in internal secretions, 121. The clone resemblances and interrelations of the different in- ternal secretions, 12^. Relation between the internal secre- Contents xi CHAPTER PAGE ion/ and nerrous systems, 128. Composition and nature of (he autonomic system, !..",>. Experimental evidence of connection between the adrenal gl-ands and the nervous sys- tem, 1.11. Clinical evidence of adrenal-nervous connection, 133. Sum mar if of present state of knowledge in this field, 137. XIX. THE ORGANISMAL SIGNIFICANCE OF THE INTERNAL SECRETORY SYSTEM 141 Genera] inability of elementalism to interpret the phenom- ena, 1'fl. Cri/!2. An illustra- tion of neglect of fact by elemenlalist theory, 1~>7. A peculiar elementalist objection to the organic whole, 13S. XX. NEURAL IXTEGRATIOX 161 Distinction, between developmental and functional integra- tion, 161. Neural and not psychical phenomena the subject of this chapter, 161. The authors indebtedness to Sher- ring ton's work, 16.'. The fundamentally of cellular inte- gration in the re-flex-arc, 163. The integration of reflex- arcx. }>;s. The spreading and compounding of reflexes, 171. Antagonistic re-flexes in skeletal muscle groups finally in- tegral ire, // '/. The antagonisms within the autonomic sys- tem finally integratire, 178. Concluding remarks on the sig- nificance of neural integration for the organismal standpoint, 1X3. XXI. IMPLICATIONS OF THE TROPISTIC AXD SEGMENTAL THEORIES OF XEHVE ACTION ......... 185 Neglect of the works of Sherrington and Cannon by Jacques Loeb, 18o. The real importance of Loeb's conception of the nerrous system, 7p-, figure 36). Throughout their career these bodies or granules are highly stainable with certain dye-stuffs. Out of the idiosome (3, figure 37) which as a rule is a body "fur sich" -in itself alone — develops the perforatorium, or head cap of the adult sperm (h.c., figure 36). It is agreed that the mitochondria (4, figure 37) in the spermatids of many animals, particularly of many vertebrates "furnish the material" for the spiral found in the connecting piece (c.p., figure 36) of the sperm. Although no spiral is present in the Seal sperm it may be represented, according to Oliver, by numerous granules sur- rounding the axial filament in the connecting piece. But while the connecting piece of the Seal sperm seems not to be typical as regards the spiral, it presents another structure, the caudal tube, or "manchette" of some authors, in a form which is specially instructive from our standpoint. In the adult sperm this struc- ture is a thin sheath enveloping the cytoplasmic part of the con- necting piece and lying in close contact with the persisting cell membrane. The point of special interest about it is that its persistence in the completed sperm of the Seal appears to be exceptional, for it is known to disappear entirely in the course of development of the sperm of several other mammals. It is a transitory or embryonic organ in some species of sperm, but a permanent one in other species, just as gills, for example, are transitory organs in the ontogeny of some species, as a frog, but are permanent in others, as fish. The development of the tube in the Seal sperm is especially favorable for observation. "It may be readily followed," writes V V Oliver, "from its first appearance up to its final incorporation in the connecting piece as a peripheral layer, or sheath." 4 Here then is a structure having all the essential marks of devel- opment due to heredity and likewise one the "physical basis" of which has been carefully observed. Mentioning a long list of investigators who believe in the "derivation of the caudal tube by a process of cytoplasmic differentiation alone" Miss Oliver tells us that her study of the development of the fur seal sperm is a complete confirmation of this view. As to the very begin- ning of the tube we read: "Shortly after the centrosomes and their tail filament have reached the nuclear membrane there appears in the cytoplasm surrounding the axial thread a series 8 The Unity of tlie Organism of delicate filaments attached to the nuclear membrane. The proximal ends of these arise in a circle around the basal end of the nucleus with the centrosomes as a center, while their distal ends project freely into the cytoplasm." 5 (figure 4-0 c.t.f.} These filaments "are at first very short and thin, but they in- crease in length and thickness rapidly. By the progressive dif- ferentiation of the cytoplasm between them they soon fuse into a hyaline tube, surrounding the axial thread and open at its lower extremity." (figure 41, c.t.) The capital point is that we have here a well-defined structure the development of which is in- an FIGURE 41. SPERMATID OF FUR SEAL (AFTER OLIVER). h.c., head cap. c.t., caudal tube, an., annulus. dubitably proved to depend primarily on parts of the cell other than the chromatin. Indeed no one, apparently, has pretended that the chromatin takes a part in its production, for even those investigators who have not believed that it arises from the cyto- plasm alone have held that it originates from the membrane of the nucleus. About the chromatoid body (-5) and the "spindle remnant" (6} (figure 37), little need be said in this connection as they seem to be inconstant structures the significance of which is in much doubt. Finally, mention should be made of the fact that a con- siderable portion of the cytoplasm is cast off entirely in the ontogeny of the sperm of many animals, as for example the seal, Evidence from Metazoan Germ-Cells 9 the body (c. r., figure 36) being all that is left of the substance at the late stage represented. So much by way of illustration of the portions of the spermatid, or germ of the spermatozoon, in the vertebrated animals, for despite the great variety in struct- ural details presented by the sperm of this part of the animal kingdom I think all will agree that so far as concerns the chief point being made in this discussion, what we have presented is true of the whole phylum. (b) Illustrated by the Ontogeny of an Insect Sperm We will now examine the ontogeny of a very different type of sperm, from another portion of the animal kingdom, the insecta. The particular species chosen is the fowl-tick (Argas miniatus). The investigation made use of is by Doctor D. B. Casteel. The series of figures (42 a, b, c, d, e, f, g,) will help to an understanding of the remarkable, almost unique sperm and spermogenesis in this animal. Figure 42a shows the nearly ma- ture primary spermatocyte. Especially to be noted are the mitochondria, mi., scattered uniformly through the cytoplasm, and the striated layer, s. L, on the outer surface of the cell. This layer is sharply demarked from the underlying cytoplasm. The striae, disposed perpendicular to the surface of the cell, are excessively fine, and when looked at in situ end on "suggest the appearance of a faceted compound eye or of honey-comb." 6 Concerning the genesis of this layer Casteel says, in a personal letter, that the layer begins to appear at the surface and grad- ually increases in depth until the completed state shown in figure 42a is reached. 'The striae," he says, "appear to be forming from the undifferentiated cytoplasm sheath." All the figures from 42 b to g have to do with the transforma- tion of the spermatid (figure 42b) into the spermatozoon. From figure 42b one sees that the striated layer has disappeared on one side of the cell and thinned out greatly in a smaller area on the opposite side; that the nucleus, n, has moved to the surface of the cell in the middle of the area of disappearance of the striated layer; that the large plasmosomes, pi. 42a have almost entirely disappeared from the nucleus; that the vesicular bodies v.b., as- sembled for the most part in the vicinity of the nucleus, are q " M£ FIGURE 42. FIGURE 42. DEVELOPMENT OF SPERM OF ARGAS MINIATUS (AFTER CASTEEL). a., ru})ture point of outer tube, c.p., cilia-like processes, fl., flagel- lum. f.p., finger-form process, g.e., gelatinous envelop, i.e., in- 10 :x-- St. n.— fl.- /I _— \. m FIGURE 42. vagination cavity, i.t., inner tube, mi., mitochondria, m.r., mito- chondrial ring, n., nucleus, o.d., oil droplet, o.t., outer tube, pi., plasmosome. s.l., striated layer, v.b., vesicular bodies, b.p., begin- ning of inner tube. 11 The Unity of the Organism in processes of degeneration and disappearance; and that the mitochondria, mi, look as though they had collected into two well-defined spherical masses m.r., on the side of the cell oppo- site the nucleus and near the small area of thinned-out striated layer. As a matter of fact these two apparent mitochondrial masses are the opposite sides of a ring seen in optical section. Transformation of the general form of the spermatid now be- gins by the indentation of the side opposite the nucleus, this going on to produce first the quarter-moon shape shown at i.e., figure 42c. By the still further growth and narrowing the edges of the cup finally come together to produce the elongated cavity shown in figure 42d, o.t. This is the beginning of the outer tube which becomes long and relatively narrow as development con- tinues, (figure 42e, o.t.}. At an early period in the growth of this tube the striated layer which naturally becomes shut into the tube breaks up over most of the circumference of the tube into what resembles a dense layer of long cilia. However,, since the processes are not motile and later dissolve and produce a gela- tinous mass within the tube, their resemblance to cilia is only superficial. This account of the fate of the striated layer applies, as previously intimated, to most of the circumference of the outer tube. But the small thin area of the layer opposite the nucleus, shown in figures 42d and 42c, retains the cilia-like processes. This persistent basal patch (b.p., figure 42d) is the starting point for an important part of the future spermatozoon, the "inner tube" so called by Doctor Casteel (i.t., figure 42e). While these profound changes are going on in the portion of the spermatid opposite the nucleus, a stout, somewhat finger- like process, (f.p., figure 42d) is formed on the nuclear side of the spermatid, into the base of which the nucleus migrates. In the meantime the vesicular bodies have entirely disappeared, and the mitochondria, no longer disposed in the ring of earlier stages, have assembled into an irregular, rather diffuse mass toward the basal patch (mi., figure 42d). At the time when the outer tube has reached its maximum length and is somewhat coiled, the inner tube, starting at the basal patch previously described, begins to grow into the cavity of the outer tube. This growth continues until the inner tube is approximately as long as the outer tube. Figure 42e presents an advanced but not completed stage of growth of the inner tube i.t. In reality, according to Doctor Casteel's interpretation, the inner tube grows at the expense of the outer tube, for when the Evidence from Metazoan Germ-Cells two are of nearly equal length the entire spermatozoon is only about half as long as it was before the inner tube developed. All of the mitochondria of the cell are drawn into the inner tube as it grows, and finally form a deeply staining mass at the distal end of the tube (mi., figures 42e and 42g). During these transformatory operations the nucleus,, greatly reduced in size proportionally to the spermatozoon as a whole, has left its former place at the base of the finger-like process, and been making its way along the wall of the outer tube, bur- rowing through the gelatinous layer on the outer part of this tube (n, figure 42e). This migration continues until, when the distal end of the inner tube reaches nearly the end of the outer tube, the nucleus lies in the wall of the outer tube opposite the end of the inner tube (n, figure 42f.) The final act of transformation takes place after the sperm has left the male tick and lies in a spermatophore sac within the genital ducts of the female. This act begins with the per- foration of the end (a. figure 42f) of the outer tube by the inner tube. Through the opening thus made the whole inner tube finally passes, really by a slipping back of the outer tube, so that, the eversion of this latter being completed, the two tubes constitute one continuous tube. By this act of turning inside out, the finger-like process in which the nucleus formerly lay (figure 42d, f.p.} is brought into close proximity again with the nucleus. Some of the details of the final steps in the transformation Doctor Casteel has not yet been able to make out; but these are of little consequence for our discussion. Nor has the act of fertilization been observed. Going on the usual cri- teria, the end of the sperm containing the nucleus would be regarded as the head. But surprisingly enough, in moving, the opposite end, the end containing the mitochondria, goes foremost. This sperm and its development are so unique as con- trasted with those occurring in most animal groups, that one might be almost inclined to question whether there may not be something wrong here — whether the case may not be one of diseased growth, or the result of manipulative mal- The Unity of the Organism formation, or something else. Any such suspicion is, how- ever, completely done away with by the fact that much the same type of spermogenesis is known to occur in other ticks. Casteel cites particularly the observations of Katharine Samson on the development of the sperm of Ixodes ricinus and Ornithodes moubata as furnishing cases to which that of Argas is "in many respects parallel." After all that has been said in the previous pages, it is almost needless to point out the significance for our general contention of this remarkable case of spermogenesis. Were we living in that comfortable era of life-philosophy wherein theologians studied nature for the purpose of proving that everything in it was made to meet some human need, we could easily recognize this case as one designed expressly to assist man in refuting the false dogma of Chromatinic Omnipotence in heredity. It is hard to imagine a developmental process in which denial of form-determining power to non-chromatinic, even non-nuclear parts of the cell would be a greater folly than would be the denial of cytoplasmic "form-determination" in the production of the striated layer of the spermatid, or of the growth of the outer tube, or of the inner tube, or of the turning inside-out of the outer tube. In fact, by far the greater part of the astonishing transformations here gone through are cytoplasmic, the nuclear changes being relatively slight. It may be worth while to remind the reader again, so boldly does the real truth about hereditary substance stand out in this case, that the cardinal evil in the chromatin dogma is that it implies the denial of great masses of the most direct observational evidence we have as to what the physical bases of heredity may be, and so tends to detract attention from them. We may predict that the important research which has made known this unique case of organic genesis will pass almost unnoticed by the geneticists of our Evidence -from Metazoan Germ-Cells 15 day. Were their attention called to it they would probably frankly say that they have little interest in genesis in this sense. That the sperm here described is not peculiar in every respect to the species Argas miniatus is certain from the meager comparative information we possess, as Casteel has shown. Nevertheless not merely general analogy, but strong indications contained in even the little comparative knowledge we have in this particular case, warrant the sup- position that in some respects the sperm of the species would be peculiar to the species, to say nothing of the genus, family and so forth. The development is, consequently, due to heredity, and the cytoplasm is "inheritance material" as ascertained by direct observation. Evidence from the Ovum We now turn to the ovum to see what can be learned con- cerning hereditary substance in the development of the ovum iself. Attention should be called at the outset to the important difference between the sperm and the ovum in the kind of specialization in each. The sperm, it will be noticed, is far more specialized for its own particular life than is the ovum, this "particular life" of the sperm con- sisting in its great power of locomotion. As a consequence of this difference, the ovum as an entity has no such sharp distinction from the ovum as a germinal element as has the spermatozoon. This difference is expressed in one way by the assertion that the fertilized ovum is the individual organism in the one-celled stage of its life. No such state- ment is ever heard about the spermatozoon for the obvious reason that the sperm does not transform directly into the embryo as does the egg. From the absence of so distinctive a character of the ovum as such, it happens that the hered- ity of the ovum is not so distinguishable from the heredity of the organism of whose life it is a stage, as is the case 16 The Unity of the Organism with the sperm. Nevertheless we are bound to recognize that the egg no less than the sperm has hereditary attri- butes of its own, and that other substances than chromatin play a demonstrable part in the production of these. In- deed the main discoveries concerning what in an earlier chapter was called the promorphology of the egg are of this sort. There is one kind of promorphology that is of special importance to the present stage of this discussion. I refer to the kind known sometimes as "germinal localization" and sometimes as "organ forming substances" in the ovum. The idea, expressed in a sentence, is that in the eggs of some animals, portions of the egg destined to give rise to par- ticular parts of the future embryo are visibly different from other portions before cell division begins, in some cases even before maturation and fertilization occur. According to our understanding of heredity, these distinguishable por- tions of such eggs are themselves hereditary attributes not only of the animal species to which the eggs belong, but of the eggs, no less than are distinctive morphological features of the adult animals or of any developmental stages. The study of these attributes of eggs is peculiarly interesting since, belonging to germ-cells par excellence, if we can get observational evidence on both their origin and destination, we shall have direct evidence that one and the same substance is determined on the one hand by heredity, and on the other is a determiner in the strict genetic sense of hereditary at- tributes yet to be developed. (a) Eggs of Ascidians--The Facts Because of the great importance of the observations of E. G. Conklin in this field, and of his general views con- cerning the bearing of his observations on heredity, we shall make his work the center of our examination. One of the most important of Conklin's investigations was on the eggs Evidence from Metazoan Germ-Cells 17 of several species of Ascidians. Among the great merits of this investigation are the facts that the normal living eggs were studied with great care, and that the comparative method was employed to a considerable extent. 'i.e. cru g.v. C rt. v. FIGURE 43. DEVELOPMENT OF AX ASCIDIAX EGG (AFTER COXKI.Tx). cn., chorion. c.p., clear protoplasm, c.r., crescent of mesoderrnal substance, g.v., germinal vesicle, p.b., polar body, p.l., peripheral layer of protoplasm, t.c., test cells, y.h., yellow hemisphere of egg- yk., yolk. Three species of simple Ascidians, Ciona intestinalis, Mol- gula manliattensis and Styela partita furnished the eggs for the investigations. We will begin the examination by quoting from the sum- 18 The Unity of the Organism mary of results, and then use these as the basis of a closer scrutiny of the conclusions. Under the head "Organization of the Egg" we find : "14. In the ovocyte of Cynthia partita there is a peripheral layer of yellow protoplasm, (p. I.) a central mass of gray yolk, (//A1.) and a large clear germinal vesicle (g. v. ) which is eccentric toward the animal pole (figure 43a). These same parts are present in the eggs of other ascidians, but are differently colored. "15. When the wall of the germinal vesicle dissolves at the beginning of maturation divisions a large amount of clear protoplasm, containing dissolved oxychromatin, is liberated into the cell body. This clear protoplasm is ec- centric toward the animal pole and is distinct from the yolk and peripheral layer. "16. Immediately after the entrance of the spermatozoon the yellow and clear protoplasm flow rapidly to the lower pole, where the yellow protoplasm collects around the point of entrance ; the clear protoplasm lies at a deeper level. The yellow protoplasm then spreads out until it covers the sur- face of the lower hemisphere. This flowing of protoplasm to the point of entrance of the sperm is comparable with what takes place in many animals, though much more ex- tensive and rapid here than elsewhere (figure 43b). "18. The sperm nucleus moves from the point of en- trance toward the equator in a path which is apparently predetermined. This path lies in the plane of first cleavage and the point, just below the equator, at which the sperm nucleus stops in its upward movement, becomes the posterior pole of the embryo. The median plane and the posterior pole are probably not determined by the path of the sperma- tozoon but by the structure of the egg. All the axes of the future animal are now clearly established antero-posterior, right-left, dorso-ventral. 19. The yellow protoplasm "collects into a yellow cres- cent with its middle at the posterior pole and its horns ex- Evidence from Metazoan Germ-Cells 19 tending about half way around the egg just below the equator (figure 43c. yji.) This position it retains through- out the whole development, giving rise to the muscle and mesenchyme cells (figure 43 d. cr.) "20. . . . At the close of the first cleavage (figure 43d) the nuclei and clear protoplasm move (c.p.) into the upper hemisphere and thereafter, throughout development, this hemisphere contains most of the clear protoplasm and gives rise to the ectoderm. "21. . . . When the clear protoplasm moves into the upper hemisphere the yolk is largely collected in the lower hemisphere. This yolk-rich area gives rise to the endoderm. "24. The chief factor of localization is protoplasmic flowing ; cell division is a factor of subordinate value." 7 From the numbers given in this quotation it will be recog- nized that only a portion of the summing up of results is here presented; and it will be understood that each item in the summary represents a lengthy, detailed description in the body of the memoir. This summary we may again sum- marize as follows : By the time the first division of the egg- cell is completed the portions of the egg which are to give rise to three great groups of tissues of the future animal are distinguishable from one another by definitely visible attributes. The clear protoplasm situated at the upper pole of the cell will give rise to the external epithelium or skin; the yolk-laden protoplasm in the lower hemisphere will produce the epithelial lining of the digestive tract ; and from the yellow protoplasm gathered on the surface at the lower pole will come most of the muscle and connective tis- sue of the animal. (b) Conklin's Interpretation Passing now to a consideration of these facts in relation to heredity we must not neglect to notice the two-fold aspect 20 The Unity of the Organism of the question, namely that we have to do on the one hand with attributes of the egg itself which are results or termini of the kind that gave rise to the conception of heredity ; and on the other hand with these same attributes not as results but as causes or 'forerunners of later-appearing at- tributes, also by the same criteria due to heredity. That the egg attributes with which we are dealing are due to heredity is obvious from the fortunate circumstance that, as already indicated, the observations under review were comparative to considerable extent. Thus we have this general com- parison of the unripe eggs of the three species : "In the liv- ing eggs of Cynthia this peripheral layer is clear and trans- parent and contains uniformly but sparsely distributed yellow pigment, which seems to be associated with these small refractive spherules. ... In Ciona and Molgula also these three areas are distinguishable in the living egg before ma- turation, but not so clearly as in Cynthia. In Ciona the peripheral layer is nearly transparent, the yolk is a brown- ish red. ... In Molgula both the peripheral layer and the germinal vesicle are transparent, while the yolk is gray, with a faint lilac tinge." 8 As an example of a very definite statement of specific difference between the eggs we read, "In Ciona the same type of protoplasmic movement occurs as in Cynthia, but with certain minor differences." The evidence brought forward by Conklin of species differ- ences in eggs is not restricted by any means to Ascidians. In some of the gastropod mollusca, for example, similar re- sults were reached by a very notable research on the quanti- tative relations of various egg organs of several species of the genus Crepidula. To be explicit in a single case only, the relative volume of macromeres 3A-3D to 3a-3d was found to be 12.1:1 in Crepidula plana and 59.3:1 in C. convex. From a long series of determinations of difference, Conklin remarks : "One cannot study the eggs of different animals without being much impressed with the fact that Evidence from Metazoan Germ-Cells the distribution of yolk to the four macromeres is highly characteristic of different species and orders." Yet, as we shall have occasion to point out later, it seems certain that facts of this kind have deeper meanings than Conklin has appreciated. After all that has been said in previous pages about specific differences, the point aimed at here will be obvious. The "decidedly thicker" layer of peripheral protoplasm at the lower pole in dona than in Styela, and the brownish red yolk in dona as contrasted with the white yolk tinged with lilac in Molgula, are indeed "minor differences." But species differences in adults and in all other stages are minor as a rule. The difference between the transparent-white color of the full-grown Ciona intestinalis and the pale, green- ish yellow of the adult Molgula manhattensis is also minor as contrasted with the "same type" of organization of the two animals. But it is just this being true to type as re- gards minor differences in living beings that has given rise to the conception not only of organic species, but to a large extent, of heredity as well ; and how can any one recognize the differential color of the grown-up Ciona as compared with the grown-up Molgula as due to heredity, but refuse to recognize the differential color of the eggs of the two animals as due to the same cause? We are, then, bound to accept the attributes of the eggs as the results of heredity, and so inquire about the "physi- cal basis" or "bearers" of these attributes. And this brings us again to the main issue of this section: Have we or have we not observational evidence that any other substance or substances than chromatin contribute to the production of the egg-phenomena under consideration? Conklin's conclusions and mode of reasoning as to the bearings of his observations on heredity are so crucial for the point now engaging us that we must examine them in considerable detail. Returning to the summary of results 22 The Unity of the Organism upon which we have already drawn we read : "26. The organization of the ovocyte is not the initial organization. The yellow protoplasm (mesoplasm) of the Cynthia egg is probably derived, at least in part, from sphere material (archoplasm) which arose from the nucleus at the last ovogenic division. The yolk (endoplasm) is formed by the activity of the 'yolk matrix' (Crampton) which also is probably sphere material. The clear protoplasm (ecto- plasm) is derived from the germinal vesicle at the first maturation division. Thus many important regions of the egg come, at least in part, from the nucleus, and a method is thereby suggested of harmonizing the facts of cytoplasmic localization with the nuclear inheritance theory." Again, we find : "This truly remarkable condition in which considerable portions of the cytoplasm are traceable to the nucleus is of the utmost theoretical importance. From all sides the evidence has been accumulating that the chromo- somes are the seat of the inheritance material, until now this theory practically amounts to a demonstration. On the other hand, all students of the early history of the egg have observed that the earliest visible differentiations occur in the cytoplasm, and that the position, size and quality of the cleavage cells and of various organ bases are controlled by the cytoplasm. However, in the escape of large quanti- ties of nuclear material into the cell body, and the forma- tion there of specific protoplasmic substances we have a possible mechanism for the nuclear control of the cytoplasm, and when, as m the case of the ascidians and fresh water gastropods, these substances are definitely localized in the egg, and can be traced throughout the development until they enter into the formation of tlie particular portions of the embryo, a specific mechanism for the nuclear control of development is at hand, and the manner of harmonizing the facts of cytoplasmic organization with the nuclear inher- itance theory is clearly indicated." Evidence -from. Metazoan Germ-Cells (c) Critical Examination of Conklin's Interpretation One is struck at the outset of a critical examination of these sentences by the fact that what is claimed is that ob- servations have been made whereby a method is "suggested of harmonizing the facts of cytoplasmic localization with the nuclear inheritance theory" ; and that this suggested harmonization of sucli localization with the "nuclear in- heritance theory" (not "chromatinic inheritance theory" be it noticed) is the final count in a mass of evidence which "practically amounts to a demonstration" that the "chro- mosomes are the seat of the inheritance material." In other words objective facts which are only suggestive of a conclusion as touching the inheritance role of the whole nucleus rise to the demonstrational level as touching the same role of very small parts of the nucleus. The method by which this particular piece of logical sleight-of-hand is performed is easy to see, for though va- ried to meet the exigencies of the special case, it follows the general scheme of elementalistic interpretation with which we have become familiar. In the first place, the fact that the observations furnish very little if any direct evidence that the chromosomes cause the cytoplasmic flowing and localization is made innocuous as evidence against the chro- mosome dogma by assuming that the flowing and localization do not themselves come under heredity. That such an as- sumption is implied, in the argument seems certain from the fact that Conklin did not consider that the general theory of chromosomes as the bearers of heredity which he had espoused made it incumbent upon him to take cognizance of the fact that he himself had in reality testified that portions of the nucleus other than chromosomes are the seat of inheritance material. We have here another and a very notable case of shielding a prevalent theory by defini- tion ; that is, of shutting relevant but inimical facts away The Unity of the Organism from it by definition. That Conklin should have been un- wittingly led into this is the more surprising in that his own studies, particularly those on comparative morphology and physiology of the eggs of several groups of animals, have added largely to the proof that many of the gross attributes of the eggs themselves are subject to heredity. Indeed no biologist has expressed more positively than he the conception that the egg is the individual animal in one of its stages of development ". . . from its earliest to its latest stage an individual is one and the same organism ; the egg of a frog is a frog in an early stage of development and the characteristics of the adult frog develop out of the egg, but are not transmitted through it by some 'bearer of heredity.'"12 One wonders if Conklin really would maintain that only the attributes of an animal in the adult stage of its life are subject to heredity; or even that the attributes of any of its developmental stages are not so subject, were he con- fronted with the question in this form. Although I have been unable to find statements in his writings from which one may positively infer what his answer would be, yet several passages can be brought together which can not, I believe, be harmonized with one another, but reveal real contradiction. Thus in The Mechanism of Heredity, al- ready cited, we find : "Differentiation, and hence heredity, consists in the main in the appearance of unlike substances in protoplasm and their localization in definite regions or cells. Such a definition is as applicable to the latest stages of differentiation, such as the formation of muscle fibers, as it is to the earliest differentiations of the g-erm cells, o 7 and the one is as truly a case of inheritance as is the other. In short, different substances appear at an earlier or later stage in the development of all animals, and these substances are then sorted out and localized; this is differentiation = heredity: see above]. Physiological division of labor in- Evidence from Metazoan Germ-Cells 25 volves morphological division of substance; sorting out of functions implies sorting out of the material substratum of functions." If cytoplasmic sorting out and localization as well in the earliest as the latest stages of development constitute dif- ferentiation "and hence heredity," how, one must ask, can the hypothesis that "the chromosomes are the seat of the inheritance material" ever "practically amount to a demon- stration"? The only way, so far as I can see, to reconcile these two statements is to say that in so far as the expres- sion "seat of inheritance material" means anything, both chromosomes and cytoplasm are such seats, and hence that neither is the seat of it. But it is not enough to point out that there is contradic- tion here. We must try to discover just how so careful a reasoner as Conklin should fail to detect it, for we may feel certain that the failure is due not to mere oversight or carelessness but to some defectiveness in standpoint or gen- eral mode of procedure. Conklin fully realizes, as our quo- tations show, that movements of the cytoplasm go far to- ward determining the attributes of the eggs of Ascidians and many other animals. But the following makes the recognition still more definite: "Undoubtedly the most im- portant of all the localizing factors so far recognized are cytoplasmic movements." 14 Assuming that our contention is valid that these localiz- ing factors of the cytoplasm are inheritance factors (and the virtual admission of this by Conklin in one of the two statements which we hold to be contradictory should be noted) we have still to see by what facts and reasoning Conk- lin reaches the view that his observations support the theory that "chromosomes are the seat of inheritance mate- rial." The observations in this case which support the chromosome theory are that the three kinds of cytoplasm of the egg: the yellow protoplasm (mesoplasm), the sphere The Unity of the Organism material (archoplasm), and the clear protoplasm (ecto- plasm) come, at least in part, and at one time or another, from the nucleus. It is not claimed that the chromosomes or even chromatin can be observed to produce the cytoplas- mic localization or any of the other distinctive features of the egg, as for example the different colors characteristic of different animal species ; or the different kinds of proto- plasm in the same species. Just what can be observed as to the relation between the chromosomes and the several kinds of material which pass out of the nucleus into the cytoplasm is not much dwelt upon by Conklin in this investi- gation. The clear protoplasm (ectoplasm) he describes and figures very definitely as being the major clear mass of the germinal vesicle set free in the cytoplasm as the nuclear membrane dissolves at the beginning of maturation. The chromosomes are said to be distinguishable at this time as numerous small deeply staining bodies. They can be ob- served to collect together in the "center of the nuclear area" and certain things can be made out about the shapes, and arrangement relative to one another of the individual chromosomes ; but nothing is recorded to indicate that they take any part in the movements of the ectoplasm, much less in the production of it. Concerning the relation of the other two kinds of cyto- plasm, the yellow or mesoplasm and the sphere material or archoplasm, to the chromosomes, Conklin's description is still more meager. An investigation by Crampton, however, has given particular attention to the relation of the sphere material, or as he calls it the yolk-matrix, to the chromatin. Crampton's results are the more significant for this discus- sion in that Conklin was undoubtedly acquainted with them. As the result of several searching tests of the chemical character of the yolk-matrix, Crampton says : "In Molgula, certainly, these granular masses are not chromatin in the proper sense." Although Crampton believes the substance Evidence from Metazoan Germ-Cells called by him yolk-matrix and considered by Conklin to be the same as what he calls sphere material, arises from the nucleus, this belief rests not on direct evidence of the pass- age of the substance from the nucleus into the cytoplasm, but on the facts that when the substance is first seen in the oocyte it is a small mass situated in the cell-body or cytoplasm close in contact with the nuclear wall, and that it reacts to stains and digestive fluids in the same way that certain granular contents of the nucleus react. But Cramp- ton is very explicit in pointing out that this substance in the nucleus is not chromatin, at least of the ordinary kind. Upon treating the cells with digestive fluids it disappears from both inside and outside the nucleus, the true chromatin being then left in clear view as fine granules in the nuclear reticulum. So far as concerns the endoplasm, then, even though it be derived from sphere material and this in turn from the nu- cleus, the most trustworthy evidence we possess is to the effect that its primal nuclear source is not chromatin. In view of such facts as these, made known by Crampton and others, through what reasoning would Conklin, to whom the facts are familiar, still hold that taken all-in-all they sup- port the chromatin dogma of heredity? Readers whose minds have become sensitized to the general type of reason- ing which pervades nearly all elementalistic theorizing and makes it to some extent fallacious, will readily anticipate about how the argument will run in this case. But it will be profitable to see it in actuality. After saying that "some of the important cytoplasmic substances can be actually seen to come from the nucleus" but that "this does not indi- cate that these substances exist from the beginning in the nucleus ; on the contrary there is direct and visible evidence that they arise epigenetically," Conklin continues : "Such epigenesis, however, does not signify lack of primary organ- ization ; on the other hand all the evidence favors the view £8 The Unity of the Organism that back of the organization of the cytoplasm is the or- ganization of the chromosomes, which is definite,, determinate and primary." (Italics mine). There you have it again ! Although it is freely granted that you can see the cytoplasm in the very act of arising epigenetically and moving about to become definitely located, that is, to become organized, still what you see is no part of the real essence of the business. "Back" of this, in the chromosomes, which, be it specially noticed, can not be seen to take any active part in the operations, we must conceive is the "organization" which is "definite, determinate and primary" -in other words which is The Ultimate Cause, so far as heredity is concerned. Again I repeat, wearisome as the iteration has become, that the fallacy in this sort of reasoning is not in holding that there is some causal power "back" of the phenomena to be explained, but that all such power is located there. That is, stating the general point in its application to the special case, the fallacy lies not in holding that the chromosomes contribute something to the hereditary attributes of the ascidians and other ani- mal groups whose development Conklin investigated, but in the implied denial that the cytoplasm contributes anything to it. Conklin probably would not admit that there is real contradiction between the observations by himself and oth- ers, on the part played by cytoplasm in the early stages of development, and his contention that the evidence now "prac- tically amounts to a demonstration" of the correctness of the theory that the "chromosomes are the seat of the in- heritance material." What he would probably contend is that the observations are opposed merely to the extreme form of the chromosome theory. Thus, speaking from an angle of the general subject a little different from that of cytoplasmic localization, he writes : "This conclusion is not a refutation of the nuclear inheritance theory, but it is a Evidence from Metazoan Germ-Cells profound modification of it." 17 And still more recently he has said, "Many biologists maintain that the nucleus and more particularly the chromosomes are the exclusive seat of the 'inheritance material' and that all the 'determiners' of adult characters are located in them. Against the extreme form of this theory many general and specific objections may be urged. General objections are based upon the con- sideration that the entire cell, cytoplasm as well as nu- cleus, is concerned in differentiation and that neither is capable of embryonic development in the absence of the other. Differentiation is indeed the result of the interaction of nucleus and cytoplasm, and how then can it be said that the nucleus is the only seat of the inheritance material?" An elaborate discussion of whether the language here used can be harmonized with the statement quoted above about the demonstration of the correctness of the chromosome theory, by saying that the views expressed in the last quota- tion merely involve a "profound modification of the nuclear inheritance theory" would smack too much of pure dialectics to deserve a place in this volume. Our sole concern is with the truth about the thing itself. Conklin's position would be so far satisfactory if he would permit us to understand his statements "the entire cell, cytoplasm as well as nucleus, is concerned in differentia- tion," and the one about modification of the nuclear inheri- ance theory, to mean that cytoplasm is "inheritance mate- rial" and contains "determiners." Evidence that cytoplasm contains "determiners" is even more positive than is that for the theory that chromosomes are the seat of such things, for the simple reason that we can observe abundantly cyto- plasm in the act of producing hereditary structures, whereas we rarely observe chromosomes operating directly in this way. But such permission would not, I fear, be forthcoming. If it would be, one is at a loss to understand why the terms "hereditary substance," "physical basis of heredity," "de- 30 The Unity of the Organism terminers," "factors" and the like, constantly used in con- nection with the chromosomes are never used in connection with cytoplasm. Indeed, so well does Conklin present the general argument for the participation of cytoplasm in the development of hereditary structures that it is surpris- ing, not to say disappointing, to find him neglect to present the most specific argument we have to the same effect, name- ly that the genesis of a vast range of such structures can be directly observed to be largely due to cytoplasmic trans- formations. One other passage in Conklin's general argument is so significant that we must reproduce it. "Differentiation is indeed the result of the interaction of nucleus and cyto- plasm, and how then can it be said that the nucleus is the only seat of the inheritance material? If held rigidly, this theory involves the assumption that the cytoplasm and all other parts of the cell are the products of the chromosomes, and that therefore the chromosome and not the cell is the ultimate independent unit of structure and function ; an assumption which is contrary to fact. Furthermore, since heredity includes a series of fundamental vital processes such as assimilation, growth, division and differentiation, there is something primitive and naive in the view that this most general process can be localized in one specific part of the cell, something which recalls the long-past doctrine that the life was located in the heart or in the blood, or the ancient attempts to find the seat of the soul in the pineal gland or in the ventricles of the brain." 19 This passage contains several well-sent shafts not only against chromosomal elementalism, but against the elemen- talist standpoint generally. And I must recur again in con- nection with it, while the facts of egg organization as pre- sented by Conklin are fresh in mind, to the perception, indicated in previous chapters, that the physical-chemistry conception of the cell must be extended to the organism. If Evidence from Metazoan Germ-Cells 31 Conklin once sees the full force of this contention, he will, we may hope, be ready to let go entirely of the idea that the facts of cytoplasmic organization must be "harmonized with the nuclear inheritance theory." He will then see that there is no more necessity for harmonizing the facts of cytoplasmic organization with the nuclear inheritance the- ory than there is for harmonizing the facts of nuclear or- ganization with the theory of cytoplasmic inheritance. REFERENCE INDEX 1. Ballowitz 255 11. Conklin ('05) 101 2. Wilson, E. B. ('00) 135 12. Conklin ('08) 90 3. Ballowitz 277 13. Conklin ('08) 92 4. Oliver 489 14. Conklin ('05) 102 5. Oliver 479 15. Crampton ('99) 48 6. Casteel 646 16. Conklin ('05) 101 7. Conklin ('05) Ill 17. Conklin ('08) 98 8. Conklin ('05) 11 18. Conklin ('15) 162 9. Conklin ('05) 21 19. Conklin ('15) 163 10. Conklin ('05) 114 Chapter XV * EVIDENCE FROM SOMATIC HISTOGENESIS IN MULTICELLULAR ORGANISMS WE must now give the greatest possible concreteness to the general truths stated by Conklin that growth is the result of the interaction between nucleus and cyto- plasm and that heredity includes such fundamental vital processes as assimilation, growth, division, and differentia- tion. But the one and only way, I again insist, to attain concreteness and certainty in the matter is through a maxi- mum of observation coupled with a minimum of inference. That is, the goal must be reached mainly by direct study of the anatomical, histological and physiological transforma- tions through which hereditary attributes are produced. The issue can be met squarely only by a still further considera- tion of what we actually know about the participation of all sorts of elements of relatively undifferentiated cells in the production of obviously hereditary parts. The study of interactions between nucleus and cytoplasm and of as- similation growth, etc., in germ-cells is not enough. What we have seen in preceding pages about the development of organs in the protozoa and in spermatozoa is that much toward the end sought. Our task now is to consider the local transformations by which structures are produced in multicellular organisms, especially in those which develop from eggs. The Mitochondria! Theory of Heredity This task may well begin by examining the recent efforts to locate the "hereditary units" in the mitochondria of the 32 Evidence from Somatic Hist o genesis 33 cytoplasm instead of in the chromosomes. This effort is just as misdirected as is the effort to make chromatin the sole hereditary substance. According to the organismal conception, all life phenomena, including those of inheri- tance, consist in the activities and interactivities of an enormous number of substances and units and forces, all of which, in exhaustive analysis, are dependent upon the organ- ism as a living whole. It is, therefore, as futile to hunt in one corner as another for the physical basis of heredity in an exclusive and more or less metaphysical sense. Any one who has grasped this idea will know beforehand that the proposal to make mitochondria fully explain heredity is doomed to failure no less certainly than was the proposal to make chromosomes or any one kind of cell element play such a role. But hypotheses, the falsity of which might have been seen before they were tested, may still be useful. If those who propose them can be convinced of their fallacy in no other way than by testing them then it is better that they should be tested even though much time and labor be given to the task. Again, the evidence brought out which dis- proves an hypothesis may be highly useful in establishing some alternative general view. This result has been espe- cially striking in the case of the mitochondrial hypothesis of hereditary substance. By bringing the cell-body back into the field of interest, from which it had been largely excluded so far as heredity was concerned, by the nuclear inheritance theory, the mitochondrial hypothesis has resulted not merely in proving that mitochondria are not bearers of heredity in the elementalist sense, but that in a rational sense they are sometimes rather closely concerned in the production of hereditary structures ; and, of even greater importance, that still other cytoplasmic material is likewise so concerned. The only reason why the mitochondrial theory of hered- ity is less interesting than the chromatin theory is that there is so much less observational evidence in support of it. 34 The Unity of the Organism In fundamental principle the one is no more and no less acceptable than the other. Any half plausible suggestion that a particular minute, obscure part of the germ-cell may be a "bearer of heredity" seems to endow that part with a peculiar fascination to biol- ogists who have the elementalist habit of thinking, and this secures to it an inordinate attention until the untenability of the hypothesis is so overwhelmingly proved that even the most credulous are forced to abandon it. Several biologists have recognized something of the state of mind here indicated without, however, perceiving its real meaning. Thus in a review of the work of Meves, which will be examined presently, we read: "the new interpretation which Meves gives at this time indicates that many are still dissatisfied with the all-sufficiency of the [nuclear] theory, and are eagerly seeking and grasping, as it were, the first visible sign of any other substance which may serve to carry the hereditary qualities." The remark to be made about any statement of this kind is that the real though usually unperceived ground of dissatisfaction is not with the all-sufficiency of the nuclear theory of heredity, but with the all-sufficiency of any theory that attempts to local- ize the function of carrying heredity in some small, specific fraction of the germ-cells ; and that the attitude which Doctor Payne well characterizes as "eagerly seeking and grasping" which has marked so much of recent search after the physical basis of heredity, has a large measure of genu- ine illusion in it. Inspired by the ages-old, alluring belief that an imperceptible final cause and explanation is hidden somewhere within or behind whatever is grossly sensed, the pursuit becomes "eager and grasping," which is another way of saying that it becomes more or less irrational and fitful. The truth of these remarks is rather strikingly exempli- fied in the short, somewhat feverish history of the mitochon- Evidence from Somatic His to gene sis 35 drial theory of heredity. The meager observational support for the hypothesis that these particular cell members are generally bearers of heredity relieves us from the necessity of examining it in any such detail as we examined the chro- mosome theory. But there are several things about it of so much importance that we must look into it somewhat. The name mitochondria was first used by Benda for a "new cell organ, perhaps serving a specific function." Benda's original view was that the function served is that of the motility of the cell. But in a later publication he presented observations which seemed to him conclusive proof that the mitochondria of the sperm are situated in parts of it which enter the egg at fertilization. This last suggestion gave an added impulse to the study of the bodies occurring in the cytoplasm and soon many new names were applied to them, for they were soon found to present differences in size, shape, and reaction to chemicals. It seems, however, that the present state of knowledge justifies us in applying to them all the one term, mitochondria, though without imply- ing that they are all exactly alike. They may be held to be generically alike but specifically different. The first investigator to set up definitely the hypothesis that cytoplasmic elements of this class are bearers of hered- itary qualities seems to have been Meves. Only a few of the very many investigations since devoted to the subject can be noticed, these being selected for their bearing on particular aspects of the problem. In the first place, the position of Meves himself is important. Accept- ing the assumptions formulated by O. Hertwig in 1875 of a "substance which carries over the beginnings (Anlagen) of the parents to the child," and that "this substance exists (in the germ-cells) in an original, histologically undifferen- tiated condition" ; 3 and adding his own reflection that not all the cytoplasmic parts of the spermatozoon (for example, the axial fiber of the tail) possess inheritance potencies, he 36 The Unity of the Organism advanced the hypothesis that the mitochondria answer the conditions of Hertwig's theory for the cytoplasmic part of the male, though probably not of the female germ-cells. Thus Meves reached the rather attractive conception that "heredity is accomplished through protoplasm and nucleus together." Were we to know no more than this about his theory we might suppose his position to be that of a genuine integrationist. However, his very next sentence does not permit us to question any further the orthodoxy of his ele- mentalism. "The qualities of the nucleus," he says, "are carried over by the chromosomes, those of the plasma by the chondriosomes." In other words the working together of nucleus and cytoplasm which he conceives is not of the sort which makes the part played by each contribute to all the results, but that one set of elements produces its partic- ular part of the total effects, while another set produces another part of the effects. The Mitochondria} Theory Tested by the Ontogeny of the Spermatozoa The utter inadequacy of this hypothesis is shown by some of the same evidence which revealed to us the inadequacy of the chromatin theory, namely that when we come to study the histogenetic processes by which innumerable hereditary attributes are produced, we find portions of the cytoplasm other than the mitochondria taking the leading part in the production. Perhaps no single one of the many instances examined by us of cytoplasmic participation in the produc- tion of attributes refutes Meves' hypothesis more complete- ly and instructively than that of the developing sperm of the fowl tick already described. We have already examined this case as one of special weight in proving that the cell-body ^ in contradistinction to the nucleus, is hereditary substance. Now we must see the conclusiveness Evidence from Somatic Hist ogene sis 37 with which this particular ontogeny disposes of the mitochondria! hypothesis of heredity so far as this case is concerned. Recurrence to the description and figures (42 a, b, c, d, e, f ) will recall that the mitochondria, widely distributed through the cyto- plasm in the early spermatocyte (?HZ.) assemble into a rather sharply defined ring-shaped mass (m.r., figure 42b) as the cell transformation proceeds., and finally take a position in the devel- oping sperm about as remote as they can get from some of the most actively and fundamentally changing parts of the organism. (mi.f figures 42 e, f, g). There is no more possibility of explaining the development of many of the parts of this sperm, the outer sheath, for example (o.t., figures S6e and f ) as due to the influence of the mitochondria than as due to the influence of the nucleus. And I point out again for the hundredth time what the real issue is here. The observations certainly do not exclude the possibility that the mitochondria exercise some invisible influence on the development of, say, the outer sheath. There may be or there may not be such an influence. But the observations do show conclusively that cytoplasmic portions of the cell other than mitochondria are operative in producing the outer sheath. It should be said in concluding this reference to the sperm of the chicken tick that Casteel finds the mitochondria located finally in the end of the sperm opposite that which contains the nucleus ; and that this end goes ahead in locomotion, the motion being pro- duced by a circlet of mobile processes at this end. From this he believes that the contractile elements are mitochondrial in origin. The conjecture that the mitochondria of the spermatocyte take part in producing the motor elements of the sperm tail is perhaps strengthened by the observations of other students, notably Lewis and Robertson. These investigators were able to follow the mito- chondria in the ontogeny of the living sperm directly into the tail, where they transform into two equal threads situated along- side the axial filament. The Mitocliondrial Theory Tested by Histogenesis If this hypothesis that mitochondria in developing sperm cells give rise to the motion-producing structures of the sperm tail, then the mitochondria would be genuine "inheri- tance material" for these particular elements, the hereditari- 38 The Unity of tlie Organism ness of the motile elements being especially striking in the case of the chicken tick sperm from the fact that the mode • of locomotion in this spermatozoon is almost unique. But while the case of mitochondria and other non-nuclear parts of the cell in the development of the spermatozoa, ought to be conclusive that although mitochondria can not be "hered- itary units" in any general sense, they, as well as other cytoplasmic parts, may contribute to the production of hereditary structures, yet it would not be so accepted, prob- ably, by the most exacting theorists because such biologists would not allow that a spermatozoon, being unicellular, can have organs and parts which are subject to heredity "in the strict sense" (i.e. in the sense of the definition of hered- ity set up by these persons). We must, consequently, pro- ceed to the specific task of this section ; namely that of considering what is known about the part played by mito- chondria in the histogenesis of hereditary structures in multi-cellular organisms. Nearly all the studies centered upon the question of whether the mitochondria are bearers of heredity have gone on the assumption, quite inadequate according to my view, that the problem is to be solved by ascertaining whether or not the bodies are persistent cell organs, take a definite part in fertilization, and are contributed in equal quantity by the female and male germ-cells. In other words the assump- tion has been that the same criteria which have been relied upon to prove that chromosomes are bearers of heredity, must also be applied for deciding whether or not mitochon- dria have the same office. But numerous studies have also aimed to follow the mitochondria in the genesis of tissues, and herein lies the chief importance of investigations in this domain. Not only have they greatly increased our knowledge about the role played by various parts of the cell in histogenesis, notably of the cytoplasmic parts, but they have put us in possession of much precise information Evidence from Somatic His to genesis 39 as to what "hereditary substance" is. The results and conclusions thus far reached are on the whole so diverse, often so conflicting, that any attempt at a general review of them would be useless for this discussion. However, certain of the results, actual or claimed, are im- portant. For example, at one extreme it is contended that the mitochondria are the immediate precursors of the most distinctive elements of ah1 classes of adult tissues. Thus Meves : "All these differentiations (of embryonic cells into tissue cells) however heterogeneous they may be, arise through the metamorphosis of one and the same elementary constituent of the plasma, the chondriosomes. The chondri- osomes are the material substratum lying at the basis of the processes of differentiation, which become the specific sub- stances of the different tissues." As an extension of this view we learn from Lewis and Lewis and other reviewers that the following tissues are reported on the authority of a long list of workers to be produced by the mitochondria: fibrillae, myofibrillae, fibrillae of epithelial cells, corneous sub- stance, secretory granules, fat, leuco-, chloro- and chromo- plasts, the test substance in foraminifera, and various other tissue elements. But several investigators, notably E. V. Cowdry, have shown the inconclusiveness of the evidence on which the con- tention is based that neurofibrils originate from mitochon- dria. "There is no evidence," Cowdry says, "that mito- chondria are transformed into neurofibrils. . . . The mi- tochondria do not show, either by a variation in their morphology, staining reactions, or in any other fashion, . . . indications of being transformed into material of dif- ferent chemical composition." 7 Furthermore, lie shows that the mitochondria do not diminish in quantity in any way commensurate with the increase of neurofibrils, as the neu- roblasts transform into ganglionic cells. Eminently worthy of note, as bearing on our contention made some pages 40 The Unity of the Organism back, that cytoplasm itself is hereditary substance, is Cow- dry's detailed description of neurofibrils as a "differentia- tion of the ground substance" of the neuroblasts. And in a later paper the same author makes a strong case of the view that while mitochondria are "associated in some way with the formation of many substances," it is highly im- probable that they transform into them. On the whole the tendency of the latest investigations appears to be to deny that the bodies produce, in a strict sense, any tissue elements. Thus as a result of their quite remarkable studies on mitochondria of living cells Lewis and Lewis say, following the enumeration given above : "The above theories seem impossible to correlate. It seems evi- dent that the mitochondria are too universal in all kinds of cells to have the function of forming any one of the above structures of differentiated tissue, and in the light of what cytological chemistry is known, it appears practically impossible for the mitochondria to form all the cell struc- tures mentioned above. In view of the fact that the mito- chondria are found not only in almost all animal cells but in plant cells as well it seems more probable that they play a role in the more general physiology of the cell." The idea that the mitochondria are primarily concerned with the metabolism of the cell appears to be gaining ground under the present comprehensive and critical methods of investi- gation that are being applied to them. The Untenable Hypothesis that the Cytoplasm of the Ovum is Inheritance Material for General but not for Special Characters A number of biologists have recently put forward the hypothesis that while the cytoplasm of the egg-cell may be "hereditary material" for certain of the general attributes of the organisms, chromosomes ' "carry" the hereditary, Evidence from Somatic Hist ogene sis 41 of the more specific attributes. This conception has arisen from a considerable range of observations to the effect that for quite a time in the "early ontogeny of many animals some of the attributes of the embryo can be seen to come directly from the cytoplasm of the egg. Thus both Driesch and Loeb have taken special notice of the fact that, as expressed by Loeb, "when the protoplasm of the egg possesses a strik- ing pigment the larva will possess the same for some time at least" ; and that "if such an egg is hybridized with the sperm of a form whose egg is unpigmented, the larva will, of course, possess a 'maternal' quality which is due solely to the protoplasm (Driesch)".1* And in the same connec- tion, Loeb continues : "It is obvious, then, that during the first stages of development an influence of the protoplasm upon heredity may make itself felt, which will disappear as soon as the protoplasm of the egg has been transformed into the tissues of the embryo." One of the cardinal questions we have to consider may be formulated in connection with this last quotation: Have we a right to assume that because an obvious influence of the protoplasm upon heredity dis- appears on the transformation of the protoplasm into tis- sue, therefore all such influence of the protoplasm ceases? To answer this question through observations upon the protoplasm of the cells concerned just before, during, and just after the transformations is exactly the central aim of this section. I can not refrain from making use of another sentence from Loeb to aid in defining the problem more clearly. "It does not seem to me," he writes, "that a discussion as to the relative influence of protoplasm and nucleus upon heredity will prove very fertile, but that it is necessary to transfer this problem as soon as possible from the field of histology to that of chemistry or physical chem- istry." I quite agree that "discussion as to the relative influence of protoplasm and nucleus upon heredity" can not be very fruitful. But the grounds of my skepticism are The Unity of the Organism widely different from those of Loeb. According to my view, the question is not one to be settled by discussion at all, but by observation coupled with a measure of consistent reasoning. Assuming that I am right, to "transfer" the problem "from the field of histology" if this really means, as it seems to, that the problem should be taken away from histology, no matter whether to the field of chemistry or any other, would be to remove it all the further from ob- servation and plunge it so much the deeper into discussion. I have not the slightest doubt that chemistry, especially biochemistry pursued on the principles of physical chem- istry, will have to be made large use of before the fullest possible understanding of the mechanism of heredity is reached. But this use will have to go hand in hand not only with morphological studies on germ-cells, but as well on hosts of cells during the whole ontogeny. Chemical in- vestigation will have to supplement, it cannot supplant, it cannot even lead, histogenic investigation. If there is one thing made more positive than any other about heredity by modern study of the subject, it is that heredity is some- thing which pertains to the smaller taxonomic grades of organisms, races, varieties, species and so forth. It wrould seem, accordingly, that hardly any suggestion for the study of heredity could be wider of the mark than one to trans- fer it from the only field which makes any pretense of in- vestigating the details of development, and taking it into a field like that of physico-chemical activity, which is no- toriously devoid of the very attributes without which there would be no such thing as heredity. Having once ascer- tained by observation as much as possible about how hered- itary attributes are actually produced, it will then be in order to learn as much as possible about the chemistry of the processes. Chemistry can do its share in solving the problems of heredity after and not before histogenesis has done its share. Evidence from Somatic Histogenesis 43 Conklin has expressed more definitely than any other biol- ogist with whose writings I am acquainted, the idea men- tioned above, that cytoplasm "influences" heredity in early ontogenetic stages, and also influences adult attributes of the major taxonomic groups, but becomes inoperative in the later stages of development, the heredity of these being transferred to the nucleus. He says, "In short, the egg cytoplasm fixes the general type of development and the sperm and egg nuclei supply only the details." And fur- ther: "We are vertebrates because our mothers were vertebrates and produced eggs of the vertebrate pattern ; but the color of our skin and hair and eyes, our sex, stature, and mental peculiarities were determined by the sperm as well as by the egg from which we came. There is evidence that the chromosomes of the egg and sperm are the seat of the differential factors or determiners for Mendelian char- acters, while the general polarity, S}Tmmetry, and pattern of the embryo are determined by the cytoplasm of the egg." If two points in this last quotation be viewed in the light of a large mass of relevant evidence not usually taken into account in recent discussions on heredity, and if strict consistency in the use of terms be maintained, the general conclusion will be quite different from that stated by Conklin. These two points, the conception of "differen- tial" and of "determiner," must now receive attention ; but first I will illustrate my position by a case presenting the kind of evidence to which I have referred. Species Attributes in Single Cells of Adult Organisms In general, this evidence comes from the field of histology, or more strictly histogenesis. The most convincing, because the most direct, evidence from this source is that pertaining to the development of hereditary structures in adult meta- zoa and metaphyta. The structures in such organisms The Unity of the Organism which are the most indubitably hereditary are those which distinguish the smaller but yet definite taxonomic groups. A little consideration will convince one that about the most crucial cases would be those in which the development of differential attributes could be traced directly to cell struc- ture and development. It so happens that vast as is our knowledge of histogenesis, the part of it which answers directly to the requirements here laid down is by no means large. The Spmules of the Ascidian Genus Styela The best instances I have been able to find are super- ficial appendages in some animals and plants, so small that they consist of a few cells or even of a single cell. One strik- ing instance of this sort has come to light in my own studies. a. FIGURE 44. SPINULE CELL OF STYELA YAKUTATENSTS (AFTER HUNTSMAK). n., nucleus. It is that of the minute spines which cover the inner surface of the branchial siphon in some species of the ascidian group of Styalids. Huntsman first called attention to the fact that each spinule is a single cell, and that at least in some cases the structures furnish differentiating attributes for species. Miss Forsyth and I have reexamined the point for Styela montereyensis and S. yakutatensis, and are able to Evidence from Somatic Histogenesis 45 confirm Huntsman's results. As Huntsman had opportun- ity to study the matter in a larger number of species than Miss Forsyth and I have had, the following description is taken largely from his paper. Figures 44a, b, 45, 46 are from Huntsman and figure 47 is from Hitter and Forsyth. By comparing figures of what may be called the dorsal view (figures 44a, 45, 46) with the side view (figure 44b) it is seen that the distinctive feature about the cell which con- stitutes the spinule is a shield-like plate on one side of the somewhat elongated cell, the distal end of which projects more or less beyond the cell body, the whole • resembling to FIGURE 45. SPINULE CELL OF STYE LA PLICATA (AFTER HUNTSMAN). some extent the end of a finger with its nail. The shield is harder than the rest of the ceU, and is probably com- posed of the same material as the general "test" of Ascid- ians, animal cellulose. The spinules are so placed that the basal portion is embedded in the surface layer of the test on the inside of the siphon, the shield being on the free side of the cell with its free edge pointed toward the lumen of the siphon. The specific attributes furnished by the spinules depend upon the shape and structure of the shields. The free edges may be truncate (figure 44, S. yakuta- tensis), or long-pointed (figure 46, S. greeleyi), or low- conical (figures 45, 47, S. plicata, S. montereyensis). Again the edge may be smooth (figures 46, 47, S. greeleyi The Unity of the Organism and A^. montereyensis) 9 or it may be serrate (figures 44, 45 S. yakutatensis, S. plicata). Viewing this case in the light of considerations put for- ward on the preceding pages, the pertinent queries about the heredity of the shields almost ask themselves : What is FIGURE 46. SPINULE CELL OF STYELA GREELEYI (AFTER HUNTSMAN) . the "inheritance material" that causes the shield to be short and truncate in S. yakutatensis and long-pointed in S. greeleyi; or that explains the serrated edge in S. yakuta- tensis and S. plicata as contrasted with the smooth edge in S. montereyensis and S. greeleyi? Is the "seat" of that ma- terial in the cytoplasm or the nucleus of the shield-produc- ing cell? Unfortunately we have no direct observational information about the genesis of the spinules. But the Evidence from Somatic Histogenesis indirect evidence which bears on the point favors over- whelmingly the view that the cytoplasm is chiefly responsible for the shield. Huntsman supposes the spinules to be de- rived from the cells of the cellulose tunic characteristic of ascidians. He may be right in this ; but it may be, too, that they are derived from the epithelial lining of the siphon. The matrix of the cellulose tunic is undoubtedly largely if not wholly produced by the ectodermal cells. It is usually held to be secreted by these cells; but in some cases, in FIGURE 47. SPIXULE CELL OF STYELA MOXTEREYENSIS (AFTER RITTER AND FORSYTH). Perophora for example, a portion of the cytoplasm of the cells seems to become transformed into the cellulose. The process of transformation can be particularly well seen in the cells which line the branchial siphon of developing blas- tozooids as shown in figure 32, plate III of my memoir.12 The parts of the cell-bodies turned toward the cellulose are here long drawn out and the protoplasm gradually becomes indistinguishable from the surrounding cellulose substance in which it is imbedded. If now we imagine this protoplasm to transform not into the characteristic cartilage-like cellu- lose mass spread over nearly the whole surface of the body, that from innumerable cells fusing into a common mass, but each cell to retain its individuality, its protoplasm becoming the shield of a spinule, we should have what these styelids 48 The Unity of the Organism, actually present. But whatever be the cells which transform into the spin- ules, all the available evidence indicates that the cytoplasm is the chief source of the shield part of the spinule. The possibility is not excluded that the nuclear chromatin also plays some part in the development. Indeed investigations, notably those by Duesberg on the ascidian egg made since "cytoplasmic inclusions" have come into prominence are distinctly favorable to such an hypothesis. But this is very far from proving that such chromatinic influence, assuming it to exist, reduces the cytoplasm to pure passivity. In the light of what is here set forth let us examine the view expressed by Conklin and quoted above that the egg cytoplasm fixes the general type of development, while the nuclei of egg and sperm together "supply only the details." The examination should be the more cogent from the fact that Conklin's idea was based largely on his investigation of ascidian eggs, some of which pertained to the very same genus, Styela, as do the spinules just described. The reader should not fail to notice that both Conklin and myself are dealing with single cells, he having to do with egg-cells, while I am concerned with spinule cells. Nor should the fact be lost sight of that these two categories of cells stand at about opposite extremes in the life career of an individual Styela, the egg being at the very beginning, while the spinule is produced at or near the completion of adulthood. Since, however, both cells possess attributes distinctive of the species, there can be no more "filling in of details" at one end of the series than at the other, so far as concerns the differential attributes under consideration. Now comes the main point. The differential attributes of the egg-cell and early embryo, their "polarity, symmetry, and pattern," are "determined by the cytoplasm," to use Conklin's own words. What is the evidence that these attri- butes are thus determined? That of direct observation, Evidence from Somatic Histogenesis 49 as the examination of Conklin's work has shown. But if on the basis of such observation it can be asserted that attri- butes of egg and early embryo are determined by the cyto- plasm, how escape asserting that the same sort of evidence touching the production of the adult attributes, those per- taining to spinule cells, are likewise determined by the cyto- plasm? It was remarked above that if all known relevant facts were taken into account and consistency in terminology be maintained, Conklin's statement to the effect that we are vertebrates because our mothers were vertebrates and pro- duced eggs of the vertebrate type, but that our species and racial characters, color of skin and hair, and so forth, are determined by the chromatin of both parental germ-cells, would have to be greatly modified. We are now in position to see what modification is necessary. Although the state- ment is undoubtedly true that we are vertebrates because we develop from vertebrate eggs, the implication that the attributes which identify us with the human species and the Caucasian race are explained, so far as heredity is con- cerned, by the chromatin of the germ-cells, whether male or female or both, is not in accordance with all the observed facts bearing on the problem. The same kind of evidence on which the assertion is based that the embryonic charac- ters are determined by the egg cytoplasm, requires the assertion that skin and other adult characters are deter- mined by the same means. This leads to the remarks we have to make about con- sistency in the use of terms. The critical reader will hardly have failed to notice the difference in application of the word "determined" as used by Conklin in the quotation we are examining. When it is said that the color of skin, hair, stature and so on are determined by the germ-cells, the determining act or condition is far removed from that which is determined, and no direct causal connection be- 50 The Unity of the Organism tween the two is established. On the contrary in the state- ment that the polarity, symmetry and pattern of the egg are determined by the cytoplasm, the determination is im- mediate and observed. Manifestly in a literal sense "de- termined" is properly used in the second connection but not in the first. The cytoplasm is operative on the spot, so to speak, in the second case. It is concerned with an immedi- ate result. The germ-cells on the other hand are not really determiners. They are not concerned with an end result, but are if anything instigators of a long developmental series at the far end of which appear the attributes in question: skin, color and the rest. If this case of spinule production stood alone as an instance of specific characters in adult animals traceable to cytoplasmic activity of individual cells, it would be a rather small base on which to erect a general argument in favor of cytoplasm as inheritance material. But it does not stand alone. Indeed, the company to which it belongs will almost certainly be found to be legion when systematic investigation of the subject shall have been made. The Spicules of Sponges and Other Invertebrates I will cite a few more cases. In several widely separated groups of animals, spicules, usually either calcareous or silicious, are present in some of the tissues. These are often produced by one or a very few cells, and often, too, their shape, size, and probably other attributes differ from species to species even of the same genus. The spicular system reaches its greatest development and has been most studied in sponges. "The spicules of sponges," writes Sedgwick, "in the diversity, symmetry, and intricacy of their form, in the perfection and finish of their architecture, constitute some of the most astonishing ob- jects in natural history." 13 Figure 48 gives a hint of the Evidence from Somatic Hist agenesis 51 facts on which this statement is based. Although the prob- lem of what all these spicules are for does not directly con- cern us, indirectly it does, as the following further remarks of Sedgwick will indicate. "While it is pretty clear," he says, "that the main function of the skeletal structures is the support and protection of the sponge body, it is by no means easy to give explanations of the diversity and com- FIGURE 48. SPICULES OF SPONGES (AFTER LAKKESTER). plexity of form which they present. The form of the megas- cleres is probably connected with the form of the canal sys- tem with which they are in relation (F. E. Schulze) ; but the form and even the existence of the microscleres defies any reasonable explanation." And then comes this statement, highly significant for almost any discussion of heredity : "By some spongologists the small spicules are regarded as functionless, and as having on that account a greater value for classificatory purposes." If any one wishes to be convinced of the extent to which the spicule forms differ with different species, he should The Unity of the Organism consult such systematic monographs as those of Schulze and Sollas in the reports of the Challenger Expedition. A picture of such a group of spicules as that shown in figure 48 reminds one of pictures of ice crystals he has seen; and the question may well be raised, Are not these spicules in reality crystallization forms, and hence as devoid of hered- itary significance as are snow flakes? The fact that the form they have depends on the particular group of sponges to which they belong, i.e., that they follow the rules of biological taxonomy, is very strong evidence that they are FIGURE 49. DENTILOPMEXT OF A SPICULE (AFTER I.AXKESTER). genuine organic productions, and not mere crystallizations. And the further fact that they follow this rule even though many of them appear to have no functional significance in- dicates that their particular forms are due to heredity and not to modeling by extraneous influences in each individual sponge. But we are not left to such general evidence for support of the supposition that they are true organic products and subject to heredity. Their development has been studied by several zoologists and the results leave no doubt about their nature so far as this point is concerned. A single instance will be enough for our purpose, but it should be remarked that many others could be given. This is taken from the excellent summary of what is known about sponges written by Minchin for Lankester's Treatise on Zoology. 'To form a triradiate spicule three cells migrate into the parenchyma from Evidence from Somatic Hist ogene sis the dermal epithelium and become arranged in a trefoil-like figure (Figure 49). The nucleus of each cell then divides into two, in such a way that one nucleus is placed more deeply and one more super- ficially. Between each pair of sister nuclei a minute spicule ray appears, the three rays being at first distinct from each other but FIGURE 50 SEE 49. soon becoming united at the center of the system (Figure 50 tr. syst.}. As the rays grow in length the protoplasm of each actino- blast becomes aggregated around each of the two contained nuclei and finally more or less completely segmented off to form two formative cells, of which the one placed more internally travels to the tip of the spicule ray, while the other remains at the base FIGURE 51 SEE 49. b.f.c., basal formative cell, tr.syst., triradiate system. (Figure 51, b.f.c.}. The apical formative cell sooner or later dis- appears, returning, apparently, to the epithelium. The basal formative cell remains at the base of the ray (Figure 51), until this portion is secreted to its full thickness. It then migrates slowly outwards along the ray, and in the fully formed spicule is found adherent to the extreme tip." The Unity of the Organism That such a mode of development is entirely foreign to crystal production hardly needs to be remarked. But if further proof to the same effect were demanded, one other strong piece of evi- dence is the fact that most of the spicules are not composed of inorganic substance alone but have a core of organic matter. Although the technique for the examination of cytoplasm de- veloped during these last years has not, so far as I know, been applied to the spicule-producing cells of sponges, we can be reasonably sure from the study of other secretory cells what the general results will be when such application shall have been made. They will bring out numerous details not now known of how both the nucleus and the cytoplasm act during spicule pro- duction. Surely it is not necessary for me to dwell again on the main point of the evidence here presented. The nuclei of the spicule-forming cells may take an active part in pro- ducing the spicules. Indeed from our general knowledge of nuclear activities, illustrations of which were given in an earlier chapter, it is probable that such will some day be demonstrated to be the case. But the proof of nuclear activity in spicule production will not be disproof of the already observed cytoplasmic activity in spicule production. Other animals that may be mentioned in which spicules are produced in much the same way and have the same taxo- nomic diversity and constancy are the alcyonaria among coelenterates, the holothurians among echinoderms, and some of the compound ascidians, particularly of the family didemnidae. Relative to the specificity of the structures in holothurians, we have this piece of significant information : "These calcareous bodies are of great value to the system- atist in classifying the smaller groups, such as genera and species. Although their general characteristics are fairly similar within the several families, the different shapes of spicules are not sufficiently constant to be used as diagnos- tic characters of such large divisions."15 In other words, so far as these animals are concerned, should it be found, Evidence from Somatic Hist ogene sis 55 as it almost certainly will be, that the cytoplasm is "hered- itary substance" for the production of spicules, the reverse of Conklin's generalization that the cytoplasm determines the larger taxonomic features of animals while chromatin is the seat of the inheritance factors for "filling in details" turns out to be true. Species-marking details are just what we are able to see the cytoplasm fill in. The "Hairs" of Higher Plants For a few more instances of species characters in multi- cellular organisms brought down to single cells, we turn to the plant world. fl FIGURE 5-J. FIGURE 53. FIGURE 54-. FIGURE 52. TRICHOMES OF PAPAVER ORIENTALS (AFTER CANNON ). FIGURE 53. TRICHOMES OF P. PILOSUM (AFTER CANNON). FIGURE 54. TRICHOMES OF P. SOMNIFERUM (AFTER CANNON). The "hairs" or trichomes borne on the leaves, flowers and smaller stems of innumerable flowering plants are usually composed of only a few cells, so that the characters they have are often referable to the individual cells. Can- non has lately investigated these structures in several groups of plants, and while he was not aiming at the particular question now occupying us, some of his results are quite to the point for this discussion. An example of particularly distinct specificity of the hairs is presented in the following: The trichomes of the three species [of poppy] are similar .. 56 The Unity of the Organism in form and size, but they are unlike in quality of rough- ness. In Papaver orientate (52 a, b) and Papaver pilosum (53 a, b,) the distal ends of the superficial cells project be- yond the general surface of the trichome and turn out at a rather acute angle. In Papaver somniferum, however, these cells did not extend beyond the general surface, with the effect that the trichomes of this species are smooth (fig- ure 54 a, b)." 16 This is especially instructive because the attribute in question pertains to the shape and position of cells, and not to differentiation within the cells. There, consequently, is no room for even a reasonable surmise that the attribute is explained by the chromatin instead of the cytoplasm. Even though the account gives no information about the position and behavior of the nuclei of the cells, it is hardly con- ceivable that any one would maintain that the substance itself of the cell-tips is not the main factor in the out- turning of these tips characteristic of Papaver orientate (figure 52 a, b). Dealing with quite another type of trichomes, those of the walnut, Cannon writes : "A character which easily dis- tinguishes the short secreting trichomes of Juglans cali- fornica from those of Juglans regia or Juglans nigra is the length of the head-cells." 17 Both drawings and tables of measurements of the heads showing lengths and diameters are given to bring out the positiveness of the distinction. Furthermore, details of cell division and cell structure dur- ing the development of the trichomes are furnished ; so the visible evidence that the cytoplasm is "inheritance material" in this case is beyond question. What the invisible evidence may be remains for further investigation to discover, but of one thing we may be sure : no matter how many facts of development now invisible may later become visible they will not destroy the validity of the present visible evidence. How far it would be possible to go on pointing out specific Evidence -from Somatic Hist ogene sis 57 characters of plants that are referable to individual cells I do not know; but judging from the instances that come to view even in my limited knowledge of the subject it might be carried to an almost indefinite extent. Another instance which I recall from the experience of my student days is the case of mosses. The serration of the leaves, I remem- ber, was one of the features relied upon for generic and specific characteristics, and I also remember that the indi- vidual teeth often if not always consisted of one or a very few cells. Cell-wall Structures i/n Higher Plants That the cell-wall is a structure of great importance in plants is known to everybody ; and the veriest tyro in plant histology has learned something of the enormous variety and definiteness of character in different tissues and dif- ferent kinds of plants presented by this part of the cell. A very brief reference to two plant structures, pollen- grains and wood tissue, will be, perhaps, a sufficient re- minder of what there is for us in this domain. A typically formed pollen-grain is a minute spheroidal body containing two cells, one known as the antheridial or germinative cell and the other as the sterile or vegetative cell. The wall of the grain consists of an outer coat, the exine, and an inner, the intine. The elaborateness of structure which these coats may reach is astonishing if regarded in the crepuscular light of the theory that cells are "simple" things. The most dis- tinctive thing about the pollen-grain is the pollen tube which is produced on one side of the grain and through which the antheridial cell reaches the ovule in fertilization. The taxonomic variety which is our main interest just here pertains largely to the sculpturing of the surface of the exine and to the structure of the exine at the point where the pollen tube will break through. It is well known to botanists that the "spikes, warts, ridges, combs, etc." of 58 The Unity of the Organism the surface of the grains are in general definitive of taxo- nomic groups of plants. And concerning the places of emergence of the pollen tube we read: "The number of these peculiarly organized points of exit is a fixed one in each species, and often in whole genera and families." As to the way these various structures are produced we have this very definite statement : "The sculpturing upon the outer surfaces of the spores of mosses and ferns and the corresponding pollen grains of the Phanerogams can in most cases be attributed to the activity of the protoplasm surrounding the developing spores." That the main tissues of plants present taxonomic char- acters is amply illustrated in the wood-tissues. The facts concerning these tissues have been almost forced into prominence by the needs of fossil botany, though they have also been much studied as a part of ordinary plant mor- phology. The section on fossil wood in Zittel's Handbook of Palaeontology is a considerable resume of knowledge in this field, and contains numerous statements and figures which bring out impressively the general truth of the specificity of the tissues of trees. After necessary allowance is made for the strictly botanical unsatisfactoriness of many of the species and genera recognized by palaeobotanists, it is not doubted, so far as I know, that on the whole the kinds of tissue they describe do in reality represent different kinds of trees. A single illustrative quotation will serve to make concrete what is here dealt with in general terms : "The phloem segments, like those of the xylem, are divided by few-seriate pith rays into rather regular two- to four- seriate rows of cells made up of thin-walled, small-celled elements in the trunk of Zamia floridana, etc., and Stan- geria. But ... in the trunks of Cycas, Dion, Encepha- lartos, Macrozamia and doubtless most cycads, as likewise in the Cycadeoideae, sclerenchymatous elements are more or less numerously and regularly interspersed among the Evidence from Somatic Histogenesls 59 • row cells, thus giving much more strength to the stem." 20 And the author goes into considerable detail in discussing the presence and the absence of "wood tracheids," "scalari- form pittings," "border pits," "spirally thickened walls" and "sieve tubes" in the genera Zamia, Cordaites, Stangeria and Cycas. That this well-nigh endless variety of character of the cell- wall in adult plant tissues is due to the activity of the cell protoplasm appears never to be questioned by botanists so long as they are dealing with the actual structure and development of the wall. "The cell-membrane is produced by the protoplasm," we read in the section on morphology in the LeJirbuch der Botanik by Strasburger, Jost, Schenck and Karsten (llth German edition) this section being from the pen of Strasburger himself. This simple, unqualified statement of fact by Strasburger is the more noteworthy because, as we saw in another connection, he has been one of the extremists on the chromosome dogma of heredity. Reading his statement that the cell-membrane is produced by the protoplasm, with the indubitable fact in mind that this membrane presents innumerable characters which are taxonomically definitive, and hence are hereditary according to the best criteria we have of hereditary characters, it seems impossible to avoid seeing that it implies an irrec- oncilable contradiction of Strasburger's often-repeated view that the chromosomes are the sole bearers of heredity. To round out the primarily factual part of this discussion two questions remain to be considered : first, that of heredity in the main classes of tissues of multicellular organisms ; and second, that of the results being reached by the latest methods of cytoplasmic study on the behavior of different portions of the cells in the histogenesis of these tissues. What is implied in these two questions can be made clear by a special case. Is the minute structure of striated muscle tissue, for example, subject to heredity? If so, are the 60 The Unity of the Organism hereditary attributes determined by the chromatin or by the cytoplasm of the myogenic cells? Applying our usual test for hereditary structures, we ask whether or not this tissue presents attributes characteristic of the taxonomic groups, species, genera, families and so on. Here again, while we have a vast store of knowledge about the structure and genesis of muscle tissue in many kinds of animals, only incidentally, as a rule, have the studies been made from the taxonomic standpoint. The Morphology of Striated Muscle Fibers For one series of very recent studies that comes near this standpoint wre are indebted to H. E. Jordan. On the taxo- nomic aspect of the matter Jordan writes : "A quite gen- eral consensus of opinion considers them more or less closely related, and ranks them both between Crustaceans and Arachnoids. Limulus muscle, however, is in appearance very much more like vertebrate than like insect muscle ; while the muscle of the marine arthropod Anoplodactylus is of the typical insect type." 21 Of the numerous differences between the fibers of the two animals compared, reference to two will suffice for our purpose. They concern the so-called M and Z lines found in the light bands of most striated muscle tissue. What Jordan regards as one of the important re- sults of his work on Limulus muscle was the evidence secured that the Z line represents a membrane, as some observers have believed, the specially convincing evidence being the fact that the "line" is attached to the sarcolemma periph- erally and to the nuclear wall centrally. These rela- tions are lacking, he says, in the sea-spider's muscle. The M line, he tells us, is especially well developed and hence easily demonstrated in the sea-spider muscle in some states of contraction, while he failed, as have other students, to detect it at all in the Limulus muscle.22 Evidence from Somatic Histogenesis 61 So we come again to the real issue.- Assuming the Z membrane to be a cytoplasmic structure, as it has practi- cally always been held to be, are wre going to deny that the cytoplasm itself causes the peculiarity of the Z membrane in the sea-spider as compared with that in Limulus, that denial being necessitated by the dogma that the real "seat'1 of the difference is the chromatin of the nucleus operating by some invisible "factor" perhaps of the nature of an enzyme? The extent of variety in striated muscle tissue is brought impressively to view in such a comparative study as that by Marceau. His main object, is not to find differences but to discover whether in spite of structural differences they have similar traits, as if they might all be derived from a single primitive form which has undergone more or less profound modification. Of the many differences which the investigation sought to re- duce to orderliness on the basis indicated, .onlv two will be men- ml tioned. From an elaborate table of measurements of the diameter of fibers, we find the following results for the sheep and pig: 23 Maximum Minimum Average Sheep 25 ju 5fj, 15]j, Pig 4,5 5 20 The other point selected concerns "striated scleriform trans- verse bands" characteristic of the muscle fibers of the vertebrate heart. This time the animals we choose are the horse and cow. The thickness of the band is given as exactly the same in these two, but the distance between the bands is 140ju for the horse and 120jU for the cow.24 TJw Physiology of Muscle Fibers We might go on almost endlessly, pointing out slight but con- stant specific differences that involve differences in muscle struc- ture, questioning in each case whether the hereditary cause of this difference lies in the cytoplasm or chromatin of the muscle 62 The Unity of the Organism cells. But such repetition would be useless for the present dis- cussion. Striated muscle tissue is specially favorable for testing hypotheses about inheritance material from the functional side as well as from the structural side. For example, there are innu- merable differences., larger and smaller, in the limb movements of animals belonging to different species and genera. I know of no observations which precisely connect activities of this sort with muscle tissue; but information concerning the electromotor force in various animals is available. The following on the au- thoritv of Eno-lemann, taken from Winterstein will serve our f O purpose. The values are those of the "demarcation current" of galvanic electricity of heart muscle, this current being generated by making a cut surface at the base of the heart and the natural surface at the apex act as a galvanic pile:25 Animal species Electromotor force in D. Anguilla fluviatilis 0.0265 Rana esculenta 0.0311 Triton cristatus 0.0124 Tropidonotus natrix 0.036 Testudo graeca 0.022 Columba livia 0.0458 Cygnus oler 0.0168 Mus musculus v. albino 0.040 Mus rattus v. albino 0.0446 Lepus cuniculus 0.0363 These investigations appear to have been made from the stand- point of general physiology, and therefore not to have been car- ried out with the systematic exactness and exhaustiveness de- manded for taxonomic discrimination. We may consequently presume that more searching examination of the same series would considerably modify these results, but we have no reason to suppose tint they would eliminate altogether the differences due to the animal species. After due allowance is made for the purely physiological and environic causes which undoubtedly explain a great many of these differences, probably no biologist would hesi- tate to grant that many of them have an hereditary basis. Turning again to the question of the seat of the hereditary Evidencr -from Somatic Histogenesis 66 factors, we are now especially attracted by the functional aspect of the subject. To an unsophisticated physiologist studying the phenomena involved in this question, it would probably never occur that more than one answer is possible. Well-informed as such a physiologist may be supposed to be on the important part known to be played by the nucleus in the life of the cell, he would undoubtedly take it for granted that the whole nucleus, its chromatin with the rest, con- tributes in some fundamental way to the result. But unless well indoctrinated beforehand with the chromosome dogma of heredity, he would almost certainly be amazed were some one to contend seriously that the cytoplasm is not the material basis of the hereditary peculiarities exhibited. He would reply, "Why, you are virtually denying that the substance of the muscle fiber is the real seat of muscular activity, thus implying a contradiction of the 'universally accepted principle that the potential chemical energy of the muscle substance is the primary source of muscular energy in all its manifestations' 26 for surely muscular energy 'in all its manifestations' would include those elements of mus- cular activity which are hereditarily distinctive of different kinds of animals." That the cytoplasm is at least the main source of the muscle substance furnishing this energy would not be ques- tioned, probably, by any histologist, but the definiteness of view held at the present time on this subject is worth re- calling and is indicated by such statements as the following: "The energy of contraction is the transformed surface- energy of the ultimate structural elements or colloidal par- ticles (submicrons) composing the fibrils."27 Presumably there would be much difference of view among physiologists as to the validity of the chemico-physical part of Lillie's theory of muscular contraction ; but apparently there would be very little dissent from that part of his view which locates the processes, whatever their exact nature, in 64 The Unity of the Organism the muscle fibers. So it would be merely a matter of suf- ficient patience to go over all the tissue systems, epithelial, glandular, bony, nervous, and the rest, and point out nu- merous certain, and innumerable probable instances of dif- ferences for different taxonomic groups of animals, and to show that these hereditary differences are expressed pri- marily in the cytoplasm of the cells. Summary of Positive Information about the Physical Basis of Heredity We have explored a vast region of fact and theory con- cerning propagation and development in organisms, for the purpose of ascertaining what is actually known about the organs and substances by which hereditary attributes are produced. Expressing the matter in terminology familiar to current discussion on heredity, we have been trying to find what is actually known about the physical basis of heredity. If clear-cut, unequivocal information of the kind sought is contained in all we have seen, it ought to be statable in a few simple sentences. What has been accomplished may be epitomized in two such sentences: First. Overwhelming observational evidence has been se- cured that the cytoplasm of cells participates directly in the formation of organic parts which have hereditary at- tributes. Second. A great mass of evidence, partly of observation and partly of legitimate inference from the principles of organic integration, has been secured, that the chromosomes of the germ-cells in plants and animals which propagate by means of such cells, participate in the production of or- ganic parts having hereditary attributes. Any substance which plays such parts in development may be named a physical basis of heredity; and these two Evidence from Somatic Histogenesis 65 groups, or categories of knowledge must, it seems, serve as the foundation of all legitimate reasoning about such "basis of heredity," or "inheritance material," or "hereditary fac- tors," or "bearers of hereditary qualities," or whatever ex- pression for the idea be employed. REFERENCE INDEX 1. Payne 190 2. Meves 816 3. Meves 817 4. Meves 820 5. Meves 850 6. Meves 845 7. Cowdry ('14) 416 8. Cowdry ('16) 436 9. Lewis and Lewis 393 10. Loeb ('06) 181 11. Conklin, ('15) 176 12. Ritter ('93) 13. Sedgwick 82 14. Minchin ('00) 107 15. Goodrich 16. Cannon 13 17. Cannon 23 18. Goebel 367 19. Campbell 51 20. Wieland 197 21. Jordan ('16) 493 22. Jordan ('16) fig. 7 496 23. Marceau 273 24. Marceau 280 25. Winterstein Ill 26. Luciani Ill, 85 27. Lillie, R. S. ('16) 255 Chapter XVI THE INHERITANCE MATERIALS OF GERM-CELLS INITIATORS RATHER THAN DETERMINERS Antecedents of the Cytoplasmlc and Nuclear Theories of Inheritance Material FOR the purpose of calling vividly to mind the character of the evidence on which, the two propositions rest with which the last chapter ended, it will be profitable to cast a glance back on the course along which biology has come down to us, with a view to finding a sharply out- standing spot in the early growth of knowledge which led to each of them. On the botanical side such a spot in the knowledge of cytoplasm as hereditary substance, is the work of Schleiden on the microscopic structure of adult and developing plant tissues. The publication of his Ueber Phy to genesis, 1838, may be taken as the starting point of our knowledge of cellular transformation in the production of tissues. It should be remembered that the observers of that period had very hazy notions about the distinction between nucleus and cell-body, or cytoplasm. On the zoological side the publication by Ehrenberg, in 1836, of Die Infusionsthierchen als volkommene Organismen may, I think, be looked upon as the first milestone in the progress of knowledge of cytoplasmic transformation into tissue sub- stance. The ever-broadening stream of knowledge of the chromo- somes in relation to heredity is usually held to have orig- inated in the discovery forty years ago, by O. Hertwig, 66 Inheritance Materials of Germ-Cells 67 that the most essential fact in fertilization is the union of the nuclei of the male and female germ-cells. That cytoplasm is a physical basis of heredity is proved by a great body of direct observational knowledge. That the chromatin of chromosomes is a physical basis of heredity is proved by much observational knowledge when this knowl- edge is supplemented by reasoning involving the principles of biological comparison and correlation. These two masses of knowledge constitute, as already indicated, the founda- tion of all legitimate reasoning about inheritance material. Whether chromatin and cytoplasm are the only substances which participate in the formation of hereditary structures can not now be stated with certainty, though there are both observational and general grounds for believing that they are not. But into this question we need not enter in this discussion. Nor is it necessary for our purpose to inquire very particularly whether the conceptions of chromatin and cytoplasm really imply just two substances or two great classes of substances, though it is best to have in mind the undoubted fact that the latter alternative is the true one. Beyond a doubt "chromatin" and "cytoplasm" ought al- ways to be understood to mean "kinds of chromatin" and "kinds of cytoplasm." Fwnction of Chromosomes in Heredity Acquired and Secondary The question which specially concerns us here is that of what the relation is between chromatin and cytoplasm in virtue of which they play the particular roles they are found to play in producing hereditary' structures. Perhaps the most important aspect of this general question is that which the theory of phyletic evolution naturally brings up: does the evidence in hand suggest any answer to the question whether chromatin or cytoplasm is the more primitive and 68 The Unity of the Organism fundamental as hereditary substance? Surveying as we have the whole field of organic propagation, including the process in unicellular organisms as well as in multicellular, and sexless as well as sexual methods of reproduction, and taking the facts as they actually present themselves, it seems as though but one answer to this inquiry is possible: The substances included under the generic term cytoplasm are the more fundamental and primitive. The only possible way of escaping this conclusion is by excluding from the conception of heredity the vast majority of developmental phenomena presented by unicellular organ- isms and by monogenic propagation in multicellular organ- isms. As our examination of these provinces revealed, such exclusion is exactly what the chromatin dogma of heredity has undertaken, implicitly or explicitly, to fix upon biology. The utter unwarrantableness of this undertaking was made sufficiently obvious, we may assume, by the examination ; so we need spend no time on that now. All that is necessary is to remind ourselves vividly of the main positive outcome of the examination : Heredity is a universal phenomenon of the living world. It is coextensive with organic propagation and development, while "carrying heredity" by chromo- somes is, according to the evidence, very far from a uni- versal phenomenon. It is a long way from being coex- tensive with organic propagation and development. We may, consequently, proceed in our quest of a more rational, more consistent, more satisfactory conception of the purely operative side of producing hereditary structures. Pur- suing the quest, we remind ourselves of having found that only the most meager observational evidence is afforded by the protophyta and protozoa, and by monogenic metaphyta and metazoa, that chromatin is hereditary substance, while these organisms afford an overwhelming mass of such evi- dence that cytoplasm is hereditary substance. But if in the lower, more primitive moiety of the organic Inheritance Materials of Germ-Cells 69 realm, chromatin is a physical basis of heredity to only a limited extent and in a partial way but has this office widely and positively fixed in the higher moiety, the moiety, that is, in which bisexual propagation is fully established, what other conclusion can be drawn consistently with the modes of reasoning universally sanctioned by evolutionists, than that the function of "carrying hereditary qualities" by the chromosomes in higher organisms is a secondary or ac- quired, or better a delegated or assigned function? Hered- ity is far older, phylogenetically, and far broader tax- onomically than is the chromatin mechanism by which it now in part manifests itself. Under this interpretation the acquisition by chromosomes of the function of carrying heredity would belong to the same evolutional type as for example the acquisition by certain cells of the function of muscular contraction, or by certain other cells of con- ducting nervous stimuli. The advantage and satisfaction of a conception of the role of chromosomes in heredity which ranges them naturally and easily with all other or- gans and tissues of the plant and animal body will be quickly seen by every one to whom the seemingly endless chance of discovering new interrelationships and consis- tencies in living nature is one of the most rewarding things about biological investigation. While we are duly impressed with the importance of per- ceiving that chromosomes fall into the great class of other organs and tissues when considered from the standpoint of phyletic differentiation of structure and function, we should not fail to notice that within the class they hold on a number of counts a very distinct place. Probably the most distinctive of these counts, at any rate the one most important for this discussion, is the fact that while the vast majority of tissues, taking the term in its usual meaning, stand at or near the termination of the ontogenic series — are, in other words, the final stage in the series — the chro- 70 The Unity of the Organism mosomes in their function as bearers of heredity stand at the beginning. They represent the initial stage in the series. Furthermore, their function in this respect is unique as contrasted with the function of other tissues, in that while other tissues have, typically, each a single function which they perform immediately, the chromatin of a given germ- cell has a great complex of functions, namely, that of ini- tiating the development through which all the attributes of the individual during its whole life-career are developed. In a word, chromosomes of germ-cells are not determiners or carriers of determiners ; they are initiators or carriers of initiators. They may, then, be called bearers, or carriers of heredity in a very literal sense, namely in the sense that they are made use of by one individual, the parent, to carry across or transfer from itself to another individual, the child, the hereditary attributes of the species in a latent or potential state. By virtue of their being thus used, they are members of a developmental series, in which series their place is at the beginning and not at the end, the nature of the series depending on the phylogenic history of the par- ticular organism to which the particular chromosomes be- long. The Two-fold Character of the Problem of Hereditary Substance At this point it becomes a matter of the greatest im- portance for theories about hereditary substance to dis- tinguish between the problem of the operation of such sub- stance in the developing individual, and that of how such substance ever came to be hereditary substance; stated otherwise, between the problems of how any substance par- ticipates either directly or as an agent in the building up of a structure having hereditary attributes, and that of how the substance itself became impressed with the attributes, in Inheritance Materials of Germ-Cells 71 a latent state, of the progenitors of the developing in- dividual. Investigation of the first of these problems is to a large extent a matter of observation, as we have seen in the pre- ceding pages. The sub-science of histogenesis consists largely in tracing out the processes by which completed tissues arise by the transformation of less differentiated or undifferentiated cells. And when such newly arisen tissues and structures are proved to be hereditary by such evi- dence as we have called attention to, then the study of histogenesis comes to be so far a study of hereditary sub- stance. When, however, we turn to the other problem, that of how hereditary substance comes to be such, we are in a different, a much more difficult case, for so far science has succeeded in getting almost no observational hold upon it; and despite the vast discussion it has received the darkness that envelops it is hardly an iota less black than it was the day of its original formulation. But stygian as the darkness is, here, especially as to details, we yet are able to see, probably, the quarter from which light will come if ever it does come. That quarter is the physical-chemistry con- ception of the organism as a system of phases the whole of which, as a species entity, is essential to its equilibrated activities. This nature of the organism, together with some- thing akin to its internal secretory and enzymic productiv- ity, enables it, we may conjecture, by some means now wholly unknown, to reflect its totality of transferable at- tributes upon the germinal cells and to transform them into a latent state. Ungrudging acknowledgment of the complete- ness of our ignorance of how any part of a cell or any other portion of an organism becomes endowed with the capacity to develop or causally to affect the development of an organism similar to that from which it came, should be an important item in the preparation to accept any and all indubitable The Unity of the Organism facts connected with heredity, even though no causal ex- planation of them is forthcoming. The childlikeness, as Conklin well characterized it, of the belief that chromosomes are a simple and complete ex- planation of inheritance would not be so bad in itself. If it stopped there, as genuine childlikeness would, no posi- tive harm could be done. It is the making of this belief the starting point of a grand speculation which blinds the eyes and closes the mind to a vast number of facts and legitimate inferences about heredity, that plays havoc with thinking on genetics. It would be a great gain if gen- etic theory would recognize wholeheartedly that all or- ganic development, as contrasted with mere enlargement, consists more fundamentally and obviously in transforma- tion of substances than it does in unchanged continuity of substances. For under such recognition the futility of attempting to explain the transformation of one lot of substance by referring it to another lot which does not transform, or in other words to explain development by something that does not itself develop, would be manifest. That the chromosome theory of heredity in reality deep- ens rather than illumines the darkness which surrounds the problem is seen when one reflects that not only does it throw no light on the question of how the chromosomes come to be bearers of heredity, but that it creates the new and equally difficult question of how the chromosomes (which ac- cording to the theory maintain unchanged their individuality not only from generation to generation but throughout each ontogeny) are yet able to be causally operative in the cell- bodies undergoing the transformations which they actually do undergo in the developing organism. That the germ- plasm-chromosome theory of heredity could have led its devotees to sidestep the details of ontogeny, especially those of histogenesis, to the extent which our review has shown it to have done, would be unbelievable but for what is Inheritance Materials of Germ-Cells 73 actually before us in the recent history of biology. Viewing heredity as being definitively a kind of organic transformation — transformation, that is, in accordance with a pre-existing or ancestral pattern more than it is a kind of continuity- -it becomes obvious that even were the dem- onstration to become complete that the chromosomes are the only portions of the germ-cells * essential to fertiliza- tion, they still would not be proved bearers of heredity in such sense as the germ-plasm theory holds them to be. They would not because the problem of the transformations which constitute ontogeny would still be untouched. The theory would be established only when the demonstration should be produced that the chromosomes cause immedi- ately all the particular ontogenic transformations known to be hereditary. All that would be proved about heredity by demonstration that the chromosomes alone participate in fertilization would be that the chromosomes alone con- stitute the first ontogenic stage of the hereditary parts of the particular organism to which the fertilized egg gives rise. The Probability That Inheritance Material Becomes Such In Each Ontogeny But because thus far failure has attended all efforts to get knowledge of how hereditary substance is produced, are wre obliged to own that we know nothing at all, even inferentially, about its production? And is the search for such knowledge to be given up as hopeless? My answer is an energetic negative to both these questions. In the first place, there is much evidence to support the hypothesis, very general to be sure but yet by no means devoid of use- fulness, that hereditary substance becomes such in some * The utter unwarrantableness of the common assumption that as regards the male germ-cell such a demonstration is "practically com- plete" will be noticed presently. 74 The Unity of the Organism way through being subject to the metabolic processes com- mon to the whole organism. Undoubtedly the germ-plasm dogma itself has tended strongly to divert attention from this aspect of the problem of germinal material — indeed, has tended to minimize the importance of the metabolism of such material even if it has not tended to deny that the material is subject to this process. So important is it from the organismal standpoint to conceive the material basis of heredity as part and parcel of the organism generally, especially as regards the basal growth and sustentative processes, that we must examine in some fullness the evidence favorable to such a conception. In its most brazenly evidence-ignoring form, the germ-plasm dogma asserts that the female parent does not really pro- duce the eggs or the male parent the sperm, as they seem to, but that these are produced by previous germs ad in- finitum. There are, to be sure, quite a number of observ- able facts, as those of the early formation of germ-cells in several animals, that can be forced into a seeming sup- port of such a conception. But the familiar and all but uni- versal fact that multicellular organisms, plants and animals alike, are sexually immature for a shorter or longer part of their lives, the very essence of the immaturity being the un- developed state of the reproductive system, would be a sufficient refutation of the view for any mind not made impervious to facts by long and faithful sophistication. Germ-Cells Subject to Metabolism Like All Other Cells • The biological commonplace that all germ-cells, like all other cells, undergo a process of growing and maturing before they can perform their distinctive office, and that this process depends upon the retention of the germs by the parent organism, ought, as already indicated, to be a suf- ficient antidote againjst the germinal continuity fallacy, Inheritance Materials of Germ-Cells 75 even though nothing were known as to exactly what goes on in the germ while it is growing and ripening. But we are by no means without positive knowledge under this head. In fact the last few cell divisions immediately pre- ceding the ripening of both ova and spermatozoa, and the ripening processes themselves, have received searching ex- amination during the last few decades, with the result that hardly any cytological phenomena are better known than are the profound morphological changes which accompany these processes. That these changes are particularly mani- fest in the chromosomes, the assumed seat of the determiners of heredity, is one of the very things that has aroused so much interest in the processes. Nor are we wholly unin- formed about the chemical changes taking place in the growing germ-cells. Unfortunately knowledge in this field has hardly passed the stage of early infancy, but at least enough is known to warrant the assertion that the young germ-cells are subject, as are all the other cells, to the general metabolism of the organism. Chemical Changes in Germ-Cells During Parent's Ontogeny About the most striking information we have in this field is what has come from such investigations as those on the chemical changes which occur in the sex glands and other body parts during reproduction in some fishes.* Mie- scher's work was ground-breaking in this domain for it was the first to show that the "sexual organs in the salmon develop at the expense of the muscular system, and that the salmine deposited in the testis during the breeding season must be derived from the proteins of the muscle, since the * Notable among these studies are: Histochemische und physiologische Arbeit en, gescvnimelt und liermisgegeben von seinen Freunden, by Mie- cher; and Changes in the Chemical Composition of the Herring during the Reproduction Period, by Milroy. Biochemical Journ., v. in, 1908, p. 366. 76 The Unity of the Organism fish does not take any food during the period." The work of Riddle and his collaborators is producing evidence to the same effect. Such researches do not, to be sure, prove that the chem- ico-physiological changes extend to the chromosomes of the germ-cells, much less to the imaginary determiners of hered- ity in the chromosomes. But viewing the results in the light of the well-grounded general belief that the moist fundamental test of living substance is metabolic change, it is seen that any hypothesis which assumes the existence in the germ-cells of something virtually not subject to the general metabolism of the cells, assumes at the same time the burden of furnishing objective evidence that such a something does exist. As a matter of fact the prime offense of the germ-plasm- determiner hypothesis is that its very essence places it beyond the reach of scientific observation. Such truth as it may contain cannot be made really effective because it can not be proved, and such error as it may contain can not be robbed of its power for evil because it cannot be dis- proved. In a word, the hypothesis is one that belongs to the realm of dialectics primarily, and has no just claim to a place in inductive science. The Possibility of Changing Sex By Influences on the Germ But perhaps the most conclusive evidence of the funda- mental dependence of true germinal material upon the or- ganism, should somewhat fuller verification of the obser- vations be obtained, are results like those reached by Whit- man, King, Whitney, Riddle, and by R. Hertwig and his students, according to which sex may be reversed in several animal species by various conditions extraneous to the germ itself, acting on the germ-cells from which the animal is to develop. The instance of this usually regarded as best established is afforded by certain species of frogs and toads. Inheritance Materials of Germ-Cells 77 The widely known result reached by Hertwig and verified and extended by Kuschakewitsch expressed in a single sen- tence, is that the number of males and of females produced by the eggs of a given female depends upon whether the eggs are fertilized when newly ripe or when over-ripe, a great predominance of males coming from the latter class. In a tabulation of the results of four sets of experiments by Hertwig 2 almost every case shows the number of males increased when the time elapsing between deposition of the eggs and fertilization was increased, the highest percentage of males in any one lot being 759, fertilization in this in- stance having been twenty-two hours after the fertilization of the last preceding lot. In a species of toad, Bufo lentiginosus, results have been obtained just the reverse of those on the frog, that is, the proportional number of females has been experimentally increased. This was accomplished by fertilizing the eggs in water made slightly alkaline. Since frog eggs are known to absorb water when they remain long in it, as in the case of those which gave rise to a preponderance of males in the Hertwig method of experimenting; and since alkaline solutions extract water from eggs, and likewise cause them to produce a preponderance of females, Miss King drew the obvious conclusion that the quantity of water contained in eggs of these animals may be a factor in determining the sex of the animals developed from the eggs. Although Miss King recognizes that her experiments do not furnish final proof of the conclusion she draws, she believes, rightly it would seem, that they weigh heavily in that direction. "As they stand," she writes, "the results strongly suggest that sex in Bufo is determined at or near the time of fer- tilization, and that external factors acting during this pe- riod may influence the sex-determining mechanism in such a way as to cause it to produce one sex or the other. The results also seem to indicate that in Bufo sex is determined in 78 The Unity of the Organism the egg, and that it may depend in some way on the rela- tive amount of water in the egg at the time of fertiliza- tion." 3 Riddle, perhaps the most outspoken opponent of sex pre- destination now writing, strongly espouses the hypothesis that the sex to which a particular egg will give rise is de- pendent partly on the quantity of water which that egg contains. But whether water is a factor in determining sex or not, the evidence presented by Riddle, coming partly from researches by C. O. Whitman and partly from his own, constitutes, when taken with the evidence to the same effect presented by other investigators, almost if not quite com- plete proof that sex is not the hard-and-fast thing which most present-day genetic speculation would make it. Furthermore the evidence produced by these two inves- tigators seems to connect the decision as to which sex a particular egg shall give rise, with some condition of the parents. It is well known to all zoologists, in the United States at least, that at the time of his death Professor Whit- man had accumulated a vast store of data on the habits, particularly the breeding habits, of pigeons. To Doctor Riddle, who had worked with Whitman considerably, fell the task of carrying on to some extent Whitman's experi- ments and of preparing for publication the results which Whitman left in the rough. The following quotation from Riddle's paper referred to above, summarizes Whitman's results that are especially important for us now: "Whit- man found that if certain very distantly related pigeons [i.e., two individuals from different families] are mated that only male offspring resulted. If the matings were made of individuals not quite so distantly related — different genera usually — and if to this situation be added the ele- ment of overwork at reproduction [i.e., the birds not being permitted to nest their own eggs, but forced to keep laying eggs in rapid succession] then the first several pairs of Inheritance Materials of Germ-Cells 79 eggs produced in the spring will produce all or nearly all males. The last several pairs of eggs laid in autumn will produce all, or nearly all, females. At the transition period in the summer he found that some pairs, or clutches, of eggs produced both a male and a female. In these cases it was usually the first egg that produced the male ; and the sec- ond egg — laid forty hours after the first — that gave rise to a female." 4 Into Riddle's interesting discussion of Whitman's results and his own chemical studies on the eggs of pigeons and hens we need not go. Suffice it to say that it seems to me Riddle is justified by the evidence now in our possession, in his contention that "sex rests upon a quantitative and reversible basis" and that in this sense it has been controlled by conditions extraneous to the germ-cells themselves. This does not imply, as I understand, that such control would necessarily be practicable or even possible in all organisms, nor does it preclude the possibility that in some species there may be dimorphic or partially dimorphic spermatozoa or ova as regards sex production. Neither does it preclude the possibility that in some cases where a preponderance of one sex has been observed, this is due to selective mor- tality or some process other than the actual shifting of the sex tendency in the particular eggs. These several concordant bodies of testimony must, it would appear, open the eyes of biologists sooner or later to the ludicrousness of a theory that would make the parent organism hardly more than a combined culture medium and incubating oven for its germ-cells. The Determiner Conception Contrary to Ordinary Chem- ical Principles If, on the basis of such facts as we have, we try to come still closer to the questions of how the assimilative and morphogenic processes of the organism occur, whether in 80 The Unity of the Organism the production of hereditary substance or in the transform- ation of such substance into actual hereditary structures and activities, we find ourselves hedged about on every side by partial knowledge, by dubious knowledge, and by com- plete ignorance on many fundamental points. However, chemical considerations seem to point the way to future discovery. In the first place, it seems necessary to recognize that the whole germ-plasm conception as orig- inally promulgated, with its interminable system of "bear- ers" and consummators, was contrary to what is well known about chemical processes generally. Thus the continuity presented by a complex chemical operation does not consist in an unchanged series of individual entities of some sort, such as determinants and determiners are, or originally were conceived to be, but rather in a regular succession of transformations. For example, when chromic hydroxide, which is grayish-green, is dissolved in acid, a green solu- tion results, which turns to greenish violet or pure violet if allowed to stand a long time. Exactly what the chemical changes are that correspond to these color changes I do not know, and probably the information which chemists have on the subject is not exhaustive. At any rate modern chemistry conceives the phenomenon to consist in a succes- sion of reactions and transformations, the various colors and shades being attributes of the compounds that exist in the various stages along the way, and not as due to in- dividual bodies carried by the preceding stages for the express and exclusive purpose of producing the particular colors that are observed, as would be implied in such a metaphysical scheme as was the germ-plasm theory elab- orated by Weismann. Enzymic chemical action presents perhaps a still better starting point for imagining what the fundamental hered- itary processes may be than does ordinary chemical activity like that just instanced. The essence of this kind of activ- Inheritance Materials of Germ-Cells 81 ity is, as everybody knows, that in some way enzymes cause or at least facilitate transformation in other substances. Thus the attribute of solubility of the sugar into which starch is transformed, through the action of the salivary enzyme ptyalin, is not held to be due to a determiner for solubility carried by the ptyalin and passed 011 into the sugar, but rather it is recognized that solubility is one of the attributes possessed by the kind of sugar into which starch is converted by the ptyalin. The solubility is thought of rather as an attribute of the sugar and not as something once latent in the ptyalin which produced the sugar. A few details of the action of the enzyme in this case illustrate the point still better. Maltose, which is the chief if not the only sugar resulting from the action of ptyalin, is not reached by a single bound, as one might say, but. through a series of bodies known as dextrins, at least three of which have been recognized. These are amylo- erythro- and achroo-dextrin, named from the color they display when treated with iodine, the first mentioned turning blue, the second red, and the third remaining colorless. What mod- ern chemist would think of explaining the blue of the amylo- dextrin by a "determiner" for that color in the ptyalin or even in the starch, the red of the erythrodextrin by an- other determiner for red, and so on? That is the sort of explaining chemists of a century ago did, but they have long since learned not merely the futility but the scientific evil of such explanation. If it were germane to our present task we might go on and show that the gene conception in modern genetics is really a revival in biology to-day of the gene conception which passed muster in chemistry a hundred years ago, when oxygen and hydrogen were named. Such an exposi- tion would be appropriate to a history of scientific theory or to a treatise on the theory of natural knowledge, but hardly to the present work. 82 The Unity of the Organism Endorsement of E. B. Wilson's Proposal to Drop "De- terminer" From the Vocabulary of Genetics In his Croonian Lecture having1 the title The Bearing of Cytological Research on Heredity., E. B. Wilson said, "In the meantime it would be well to drop the term 'determiner' or 'determining factor' from the vocabulary of both cytol- ogy and genetics." If the facts and arguments set forth in the preceding pages are valid, they constitute a demon- stration that not only would it "be well to drop the term 'determiner,' but that it must be dropped, at least in its present application, before thought and investigation on the mechanism of heredity can be free and in very deed truth- seeking. "What we really mean to say," Wilson continues, "is 'differential' or 'differential factor,' for it has become entirely clear that every so-called unit character is pro- duced by the cooperation of a multitude of determining causes." So far as these statements go they are in strict accord with the organismal standpoint maintained in this Volume, and we may also say, with the physical-chemistry standpoint. Where attributes of adult organisms have been so defin- itely correlated with particular chromosomes and possibly parts of chromosomes of the germ-cells as seems to be the case in the fruit flies, such chromosomes are unquestionably differential, and since they stand at the very beginning of a long and complex transforming and developing series, they may very properly be called differential factors even though they do not themselves participate suhstantively in the transformation. The general similarity of their mode of action to that of enzymes is certainly considerable : a minute quantity of the substance is capable of inducing or facili- tating the transformation of a large amount of other sub- stance in a perfectly definite manner, and the inducing agent is not itself consumed. Inheritance Materials of Germ-Cells 83 Advantages of Conceiting Germ-Cell Chromosomes as Initia- tors in Hereditary Development This chemical way of viewing chromatin and chromosomes sanctions the idea that these are to be regarded as initiators of developmental processes which lead to hereditary attri- butes, rather than determiners of those attributes. If one wants to know in what way this conception would have an advantage over the determiner conception as a working hypothesis, my reply is that the advantage is two-fold. First, it would surely correct the tendency of genetic re- search under the guidance of the determiner hypothesis, to restrict its attention to attributes of adults at one end of the ontogenic series and to the chromosomes of the germ- cells at the other end, and to ignore or touch only in the lightest way all the intervening parts of the series. This correction would result because the new standpoint would bring the whole series of continuities and transformations alike into proper perspective, revealing thus that the mem- bers of the series intervening between germ and adult must be investigated in exactly the same way and with the same objects in view as the end members, if complete understand- ing of the hereditary process be the goal of research. It could not then happen that the egg-cell would be repre- sented, as it now so commonly is, as a relatively large sac containing nothing significant for heredity except the rela- tively small chromosomes. Nor could nearly the wrhole mass of ontogenic phenomena, especially those of histo- genesis, be treated so lightly in speculation and so largely neglected in investigation as they have been under the domination of the determiner theory. The second advantage in the initiator conception is that since it would recognize the "differential factor" of the chromosomes to be in reality due to the fact that the whole ontogenic series to which the chromosomes belong is differ- 84 The Unity of the Organism ential, that is, that it pertains to a particular species or kind of organism, it would put an end to the notion by which recent genetic science has been so largely dominated, that the problem of how the series came to be thus specific or differential may be solved by speculation, and it would incite geneticists to efforts to solve the problem by obser- vation aided by experiment. It is impossible to refute the charge that genetics is to-day more interested in an elab- orate system of conceptions — of speculation, in other words — than it is in observed or possibly observable phenomena. We cannot keep too constantly before our minds the fact of our almost complete ignorance of how any substance becomes hereditary substance whether through the "inheri- tance of acquired characters" or in any other way. Hence mere speculation on the subject after the manner of the pan- gens idea is much worse than nothing if permitted to run into a bewildering and enslaving system like that of the germ- plasm theory as it came from Weismann's mind. Neverthe- less it is quite germane to the present discussion to point out that whatever might be the nature of the chemical ac- tion, whether enzymic or some other, through which the series of ontogenic transformations should be accomplished, the character and subtlety of these processes seem to make them, more than any others we know, competent with some modification to serve as the go-between for impressing the germinal material with the latent attributes of the species. Inconclusweness of the C Biological Evidence Usually Ap- pealed to in Support of the Chromosome Theory And this leads to the concluding statements of this dis- cussion. The three categories of cytological fact which have been weightiest in the formation and maintenance of the chromosome theory of heredity are the individuality and continuity, chiefly numerical, of the chromosomes from par- Inheritance Materials of Germ-Cells 85 ent to offspring; the apparent equality (it should never be forgotten that the dogma of equality does not rest on rigor- ous quantitative investigation) of the chromosomes in the male and female germ-cells ; and the assumption that in the male germ-cells the chromosomes alone are concerned in fertilization. Even if these groups of assumed fact were established with absolute certainty they would fah1 far short of being direct and final proof that chromatin is the only hereditary substance. That this is true must be apparent to all well-informed, carefully thinking biologists. The most important grounds for this inconclusiveness are in- volved in the facts and arguments set forth in the preced- ing pages, but they may be summarized here, and in addi- tion two other grounds may be pointed out. First and foremost, in my opinion, is the general truth that chromosomes or even chromatic substance can not pos- sibly be recognized as the sole bearers of hereditary sub- stance, because the evidence is enormous in quantity and direct and indisputable in quality that other substances par- ticipate actively in the production of hereditary attributes. There is no way of escaping this conclusion except by nar- rowing the definition of heredity for the very purpose of bringing it within the scope of the chromosome theory of hereditary substance. The scope and fundamentally of this aspect of the problem is sufficiently dwelt upon, we may hope, in what has gone before. The two additional grounds for skepticism as to the con- clusiveness of the cytological evidence will now be pointed out. First, as to the evidence from the individuality and continuity of the chromosomes. All that any careful thinker claims or can claim for this evidence is that the individuality and continuity of chromosomes as observed are what might be expected if they were the germinal de- pository of the organism's hereditary attributes. And the question is constantly and naturally asked, what other 86 The Unity of tlie Organism meaning can the whole remarkable series of phenomena of maturation and fertilization have than that attributed to them by the chromosome theory? My rejoinder to this argument may begin with a reply to the question. As long as knowledge of the chemistry and physiology of cells— germ-cells with the rest- -is as fragmentary and inconclusive as it now is, certainty as to the meaning of the phenomena mentioned is out of the question. However, it would seem quite probable that they are concerned primarily with the nutritive and assimilative processes of the cell and only derivatively with heredity. Furthermore, the question asked may weU be paired off with another of similar character, namely, what is the meaning of the almost if not quite com- plete breaking up and disappearance of the chromosomes in the so-called resting stages of the immature germ-cells, this being accompanied by the dissolution of the nuclear mem- brane so as to allow the freest possible commingling of the whole nuclear contents with the cytoplasm of the cell? Have we not at least as much factual right to suppose that during this mixing of substances the chromatin, and so later the chromosomes, are influenced by the cytoplasm, as that the reverse influence takes place? Is it not entirely possible that this process is one of the very means or occasions of impressing the chromosomes with the attributes of the or- ganism which, as we have seen, apparently must take place whether acquired characters are ever inherited or not? And now as to the argument from the assumed exclusive participation of the chromosomes of the male germ-cell in fertilization. First of all, it can not be admitted for a moment that the chromosomes are proved to be as ex- clusively the fertilizing agents as they are generally as- sumed to be. Even in such extreme cases of seeming ex- clusiveness of chromosomal participation as that claimed by Strasburger for the pollen cells of some plants, neither Strasburger nor any one else has claimed, so far as I know, Inheritance Materials of Germ-Cells 87 that all other male substances than chromatin are excluded as rigidly as would be required by experiments in a chemical laboratory designed to ascertain the action of a particular chemical element or substance in its purity. It is certain, for example, that in almost if not quite all male germinal elements in animals, a thin outer layer from the cytoplasmic part of the spermatic! is present on the head of the sperma- tozoon. Furthermore, it is well known that at least the "intermediate piece" of the sperm tail, which is not usually regarded as chromosomal in origin, remains in the egg at fertilization. Nor is there any good ground for supposing that the non-chromatinic portions of the nucleus are ab- solutely excluded. The almost certain presence in the egg at fertilization of at least these male substances other than chromatin can by no means be regarded as insignificant for heredity, especially if the initiator conception of germinal material is held. It seems to follow of necessity that if the fertilizing substances, whatever their source, be conceived to act in an organic system of the physical chemistry sort after the manner of enzymes, no such quantitative relation subsists between these fertilizing substances and the prod- ucts of organic growth as the chromosome theory implies ; nor can their action be so narrowly localized in the eg-g-. «/ oo Their action would be conceived to involve the entire ovum ab initio, and not the chromosomes alone. Summing Up of the Findings Against the Chromosome Theory The general result of our critique is that the whole at- tempt to interpret the physical basis of heredity in accord- ance with elementalist conceptions has failed and must con- tinue to fail, so far as its main aim is concerned. We are led to see that the germ-plasm dogma, no matter how often or how completely it changes its nomenclatural habiliments, 88 The Unity of the Organism as in the shifting from determinants to determiners, or from determiners to gem, or from gens to factors, involves a rejection of the conception that the germinal elements of organisms after being discharged are literally detached parts of those organisms. This conception was well on the road to incorporation into the great body of established biological truth when it was headed off by Weismann's diametrically opposed hypothesis of germinal isolation. I would insist that the defense of the organismal concep- tion in this volume is really a carrying out of such a con- ception of the organism and its germinal products as is implied by the old view that the germ is a part of the parent organism. It would hardly be possible to express more sat- isfactorily in a single sentence the most inclusive theo- rem, as it might be called, the demonstration of which is the aim of the part of this volume devoted to the means by which organisms propagate their kind, than the following from E. B. Wilson : "To the modern student the germ is, in Huxley's words, simply a detached living portion of the substance of a preexisting living body carrying with it a definite structural organization characteristic of the species." 6 Coupling this statement by Wilson with another from one of his latest writings,5 to the effect that we ought to drop the term determiner because in reality what it means is differential, I call attention to the fact that the "dif- ferential factor" of the later statement and the "definite structural organization characteristic of the species" of the earlier statement are in essence one and the same. The only difference is that in the earlier statement it is the whole germ-cell that is recognized to be a detached part of the organism, while the later statement can be brought down to the chromosomes because of the greater refinement of knowledge attained since the earlier one was made. The point I wish to make stand forth with the greatest possible Inheritance Materials of Germ-Cells 89 boldness is that the germ-cell chromosomes may properly enough be said to be differential, if only one never loses sight of the fact that they are differential in no other sense than are any other particles or substances of the germ- cells or any other cells which participate in the production of species-attributes. Brief Reference to the Untoward Implications of the Germ- plasm Conception of Heredity The somewhat laborious task of exhibiting the difference between conceiving the physical basis of heredity from the elementalist and from the organismalist standpoints may well be brought to a close by calling attention to the impli- cation of the two conceptions as applied to heredity in man himself. Looked at from this direction the germ-plasm dogma is seen to be chargable with the grave offence of having added its weight to a conception of human life, the overcoming of which has been consciously or unconsciously man's aim throughout the whole vast drama of his hard, slow progress from lower to higher levels of civilization- the conception that his life is the result of forces against which his aspirations and efforts are impotent. As ap- plied to man this form of fatalism is no less sure and no less dire in its tendencies than have been any of the innumerable theistic forms of fatalism that have prevailed through the centuries. It is almost certain that the ardor with which Eugenics has been espoused by several biologists is due in considerable measure to the fact that they have felt more or less definitely this sinister implication of the theory, and have turned to Eugenics as the only weapon against its evil forebodings. The germ-plasmic eugenist virtually says, "Yes, indeed is man a reasoning, willing, aspiring animal, but all his activities in these ways are futile so far as the race as a whole is concerned, except as they are 90 The Unity of the Organism brought to bear, extrinsically and operatively rather than organically, on the Germ-Plasm." This form of the Eu- genic idea corresponds in spirit to the propitiative offerings of primitive religion. It aims to mollify by human agency powers that act upon men's lives, but which are in them- selves largely extraneous, largely evil, and wholly irre- sponsible. What eugenists of this school have failed to see, evidently, is that even were unit-factors as differentiate from one another in heredity as the extremest Mendelist conceives them to be, and that even were the germ-plasm improved up to the level of his highest hopes, his results in terms of ac- tual human lives and social conditions would be distressingly meager. They would be so, because whether unit-factors exist independently in heredity or not, they certainly do not exist thus independently in development and function. In these ways they interact upon one another in the most vital manner, as physiology, especially of the internal se- cretions and the nervous system, and as physiological and social psychology are rapidly and conclusively demon- strating. We thus end our examination of the means by which or- ganisms produce others of their kind with the conclusion that the material through which reproduction is accom- plished is in the most vital way part and parcel of the organism, that is, that the germ-cells are somehow stamped through and through, potentially, with the characteristics of the kind, or race, or species to which the producing or- ganism belongs. And with this we are ready to pass to the examination of those integrative phenomena of the organ- ism generally, one manifestation of which is this very nature of the germ-cells. REFERENCE INDEX 1. Marshall 292 4. Riddle 10 2. Hertwig, R. ('12) 75 5. Wilson, E. B. ('14) 351 3. King 232 6. Wilson, E. B. ('00) 7 PART II THE CONSTRUCTIVE SIDE OF THE ORGANISMAL CONCEPTION Chapter XVII " GROWTH INTEGRATION The Field to be Covered by the Constructive Discussion A CCEPTING the inevitable destructive result of our cri- ^~JL tique of the elementalist standpoint, that the attempt to interpret living beings in the terms of their constituent parts alone always leads to partial failure and disappoint- ment, or to the worse result of illusionment as to the trust- worthiness of the explanations proposed; and accepting the constructive result that everything in the critical study tends to show that no part of any organism can be rightly inter- preted except as part of an individual organism, this indi- vidual being in turn interpreted as a member of a taxonomic group, it is revealed that we are only on the threshold of the positive, the constructive side of our general enterprise. Even though the conclusion be unescapable that the living organ- ism somehow acts causally on its parts, the problem still remains as to the modus operandi of that acting. The "some- how" which came to us as an incident of our critical study has yet to be inquired into. Stated more specifically the task now before us is that of examining closely and systematically the interdependences among the parts of the individual organism. Although these interdependences are among the most obvious and general of all organic phenomena such an examination of them biol- ogy has not yet made systematically. Indeed — and here is one of the most vital things for us to see — a cardinal charge against the elementalist standpoint is that in its very nature 93 94 The Unity of the Organism it not only does not encourage, it actually stands against such examination. Its opposition to comprehensiveness and systematization is profound and essential. Our examination will begin with a single brief, two-parted definition : The structural and functional interdependence found to exist among the parts of an organism we call bio- integratedness; and the process of moving on from grade to grade of interdependence among the differentiating parts which constitutes ontogenesis in the individual we call bio- integration. Four Types of Bio-integration to Be Treated In the present state of knowledge and for the discussion now before us four types or kinds of bio-integratedness and bio-integration may be recognized as pertaining to the in- dividual organism : 1. Growth integration, most obvious in graded meristic series, but also expressed in the "axial gradients" of Child. 2. Chemico-functional integration, known so far chiefly in connection with internal secretions. 3. Neural integration, comprising the interdependences among the parts of the nervous system, and the involvement with this of the muscular, glandular and other organs. 4. Psychic integration, very closely connected with neural integration, but approached from the side of the totality of activities of living beings rather than from the side of nerve- organ activity, and so taking cognizance of a vast number of phenomena not yet definitely correlatable with neural phenomena. The full presentation of facts and arguments under these four heads would reach far beyond the limits set for the present work. We are, consequently, obliged to restrict ourselves to a small portion of the best established and most compelling evidence under each head. Growth Integration 95 Graded Repetitive Series as Integrative Phenomena This, perhaps the simplest form of integrational phenom- ena known to biology, is seen "almost everywhere, but shows itself most typically and strikingly in plants and in many lower animals. Reference is made to the gradation in the repetitive or meristic parts appearing in so many organisms. The most obvious criterion of such gradation is the rela- tive size of the parts, but, as we shall see later, there is con- siderable reason for supposing the gradation is not re- stricted to size. The few examples to which space can be given are selected to represent as wide a range as possible of the phenomena under consideration. Illustrations from Animals The lancelets, fish-like animals of the genus Amphioxws, may be noticed first (Figure 55). It will be observed that FIGURE 55 SIDE VIEW OF AMPHIOXTJS (AFTER PARKER & HASWELL). notochord. cir., cirri, or.hd., oral hood, myom., myomeres. dors.fr., dorsal fin rays, cd.f., caudal fin. gon., gonads the creature tapers off toward both ends and that the series of metameres, myom, usually called myomeres because they compose the main body-musculature, diminish not only in dorso-ventral measurement from near the middle each way, but are also thickest in the mid-region and become thinner as they progress toward each end. • Something of this size scheme of body-parts is very com- 96 The Unity of the Organism mon in the animal kingdom. Figure 56, a photograph of the skeleton of a python (see frontispiece), shows in a gen- eral way the size-relations of metameric skeletal parts in a higher vertebrate. Something of the extent to which the proportionality of parts of the individual metameres is car- ried out in this skeleton is shown by tabulating a series of measurements of the parts : Position of vertebra L.V. T.V. T.ex.zyg. H.D.S. W.D.S. L.R. 5 6 mm. 5 mm. 1 1 mm. 15 mm. 4 mm. 25 mm. 50 11 16 23 11 8 48 100 18 17.5 28.5 9 7 79 150 13 16.5 26.5 7.5 7 82.5 200 11.5 15 22.5 5.5 7.5 69.5 250 10 10.5 16.5 5 5.5 52.5 300 6 5 7 4 2 0 327 4 3 4 2 2 0 "Position of vertebra" refers to the serial number, beginning with the head-end, of the vertebra measured. Legend: L.V., Length of vertebra, measured from the posterior edge of one dorsal spine to the anterior edge of the one next behind it. T.V., thickness of vertebral centrum in its thinnest part, i.e., near the middle. T. ex. zyg., thickness of vertebra at extreme of posterior zygopophyses (articulating processes). H.D.S., height of dorsal spine. W.D.S., width of dorsal spine. L.R., length of rib. The starfishes are another class of animals which exhibit beautifully this size gradation of repeated parts, both their "tube-feet" and the calcareous skeletal supports being graded proportionately to the tapering arms of the animal. The following table presents a series of measurements of the two organ systems just mentioned, from a single arm of Astrospecten calif ornicus. The dimensions are in millimet- ers, and the series proceed from the proximal to the distal end of the arm. Growth Integration 97 TABLE Series Tube-feet Ambulacral plates Adambulacral plates number Length Length Width Thickness Length Width Thickness 5 3.9 6.4 3.1 1.2 3.8 3.6 1.0 10 3.7 3.9 2.7 1.3 3.5 2.4 1.2 15 3.5 3.5 2.4 1.3 2.8 2.2 1.4 20 3.1 2.6 2.0 1.2 2.4 2.0 1.2 25 2.2 2.3 2.0 1.0 2.1 1.9 1.1 30 2.1 2.1 1.9 0.9 1-9 1.7 1.2 35 2.3 1.8 1.6 1.0 1.7 1.3 1.1 40 1.7 1.2 l.l 0.9 1.4 1.0 1.0 45 1.8 0.8 1.0 0.6 1.0 0.8 0.9 50 1.3 0.7 0.7 0.5 0.7 0.7 0.6 55 0.9 60 0.8 65 0.7 68 0.5 Not only do these graded meristic series appear in the individual makeup of a great range of animal species, but they occur in the colonies of many species in which aggrega- tions are produced by budding. Sometimes, as in many al- cvonaria, the size gradations are very obvious, while in other groups the distinctions are so small as to be discoverable only by close quantitative study. An example of this latter is furnished by the plumularian hydroids. A typical colony of the genus here studied, Torrey writes, "closely resembles a feather, of which the shaft is represented by the stem and the veins by the two ranks of alternating branchlets, or hydro- cladia, corresponding to barbs. Each hydrocladium is divided by more or less definite nodes into internodes and bears on one aspect- -the same in all hydrocladia — a compact series of hydranths, one to each internode." Without entering into the tabular and graphic details contained in this study, the author's summarized statement concerning one of the tables will suffice: "It will be seen from the table that, as the tip of the colony is approached, not 98 The Unity of the Organism only do the hydrocladia possess fewer and fewer hydroth- ecae, but the dimensions of the latter through the mesial nematophore reaches its minimum more and more rapidly. Since the hydrothecae, once formed, do not enlarge with age, it is clear that for such colonies as this, there is a limit of growth and a specific form." This correlation and proportionality among repetitive parts is frequently observed within the bounds of particular a. FIGURE 57 — TENTACLE OF HALOCYNTHIA JOHNSONI (SCHEMATIC; AFTER HITTER). a, axis, a', axis of branch, b', b", primary and secondary branches. organs, as for example, in the branching tentacles occurring in various groups. A detailed study of one of these cases was made by me some years ago on the tentacles of an as- cidian. Figure (pi. 1£, figure 13) of this study, sup- plemented by the following statement, illustrates the point. "Although this figure is diagrammatic in a way, it is accurate as to numbers of branches. The positions, too, of all the branches and length of the primaries were deter- mined by micrometer measurements, and the secondaries were drawn as accurately as possible." 2 For the rest, the figure (Figure 57) tells its own story. Growth Integration 99 Illustrations from Plants But it is in the plant world that these graded series of homonjmous parts in individual organisms are most strik- ingly seen. It occurs in what is perhaps its most typical, least modified expression in the arrangement and size rela- tion of parts in the leaves of many ferns and palms. But the compound leaves of innumerable flowering plants illus- trate it very beautifully. Figures 58, 59, and 60 (Acacia, Vicia and Cassia) show three types of compound leaves based on the mode of gradation of the leaflets. These might FIGURE 58. ACACIA ELATA. 100 The Unity of the Organism be described as the bi-gradicnt, the direct gradient and the reverse gradient types, depending on whether the gradation is from the mid-region of the axis both ways (figure 58), from the proximal toward the distal end (figure 59), or from the distal toward the proximal end (figure 60). FIGURE 59. VICIA GIGANTEA. FIGURE 6'0. CASSIA SP. Almost all simple leaves of seed plants show something of the same scheme. As examples, typical elliptical-entire leaves of the elm and poplar and such typical lobed leaves as those of most oaks may be pointed to. Nearly every twig of a tree which represents a single annual growth impulse, in cases where the growing period is restricted to a small part of each year, presents a size gra- dient in the leaves distributed along the axis. A particularly striking illustration of this is furnished by the California Growth Integration 101 coast redwood, Sequoia semperrirens (figure 61), where the new segment is short, is added end on to the one before it until a considerable succession of segments is produced, and where the leaves are retained for several years. That each segment in these leaves is an annual production is not cer- tain, probably several segments being sometimes formed in a FIGURE 61. SEQUOIA SEMPERVTREXS. single season ; but however that may be, that growth occurs in a series of impulses, each of which is sharply recorded in the size gradations of the repeated parts, is obvious enough. It is a familiar fact, too, that in many plants a similar quantitative gradation of the reproductive parts along an axis occurs, but the extent to which this scheme pervades the constituents of the members of the series, even to the seeds, appears not to have attracted much interest on the part of botanists. To illustrate this point I present a single set of measurements, one of many which I have collected, The Unity of the Organism of parts of the fructiferous organs of plants. These meas- urements are of Frasera perryi, an abundant annual in southern California and rather specially favorable for such a study in that the fruit stalk is single in each plant, stands up intact and rigid after it is fully ripe and dry, and is al- most mathematically regular in the disposition of its parts. The table was compiled from measurements of a single plant, and three measurements pertaining to each seed vessel are given, namely, the length of the interval on the main axis between each two vessels, the length of the pedicels which bear the vessels, and the length of the vessels themselves. The measurements are all in millimeters. Several other di- mensions might have been taken, which would almost cer- tainly have produced similar results. Series Number Length of Internode Length of Pedicel Length of Capsule 1 27 36 21 2 19 29 18 3 19 32 18 4 22 34 16 5 23 29 16 6 19.5 28 17 7 18.5 25 17.5 8 17 25.5 17.5 9 19 25 18 10 18 25 16 11 18 21 16.5 12 15 21 16 13 15 22 13.5 14 15 22 14 15 15 21.5 13 That these gradations hold, at least in some plants, even to the seeds is certain as the following tabulation of the weight of seeds from different parts of the seeding axis of a wild mustard plant (Brassica nigra) shows. The figures were compiled from the weights of seeds taken from groups Growth Integration 103 of twenty capsules from the bases, middle portions, and dis- tal ends, respectiArely, of six such stalks. The weights given are in grams. Total weight Number of Seeds Av. Wt. per Seed Base .903 950 .00095 Middle .694 ?'>'! .00088 Tip .330 525 .00063 This mere glance at an exceedingly common phenomenon in living nature must suffice for the present. Justification for Bringing All These Phenomena Under One Head Probably about the first question that most persons would raise concerning what we have presented would be as to how far the series dealt with have anything to do with one an- other. Especially, we may apprehend, would most biologists question the justifiability of bringing together the raeristic phenomena in animals and the repetition of parts in plants. If such a collocation of phenomena must be justified on the basis of known causal factors, then undoubtedly is justifica- tion impossible in the present state of knowledge. But justi- fication of this sort is not called for by the point now oc- cupying us. What concerns us at present is the quite for- mal fact that when any lot of homonymous objects fall into a quantitatively graded series the members of that series have a fixed relation to the series as a whole. They are not interchangeable with one another. Each is a function, mathematically speaking, of its set or series. Vertebra m of the python's skeleton, myotome m of the amphioxus body, tube-foot in of the starfish arm, branchlet m of the ascidian tentacle, leaflet m of the vetch leaf or of the redwood shoot, seed-vessel m of Frasera, seed-lot m of the mustard plant, and m, or any other member you choose from any other 104 The Unity of the Organism series whatsoever, is a determinate thing; it is what it is partly because of its position in the series regardless of whether the physical or other producing agent of the dif- ferent series be the same or wholly different. Even this purely structural formal basis establishes the fact of a measure of integratedness for all individual organisms in which the phenomenon appears. But to leave the subject at that would be superficial and unsatisfactory indeed. However, reflection makes it almost certain that there is some sort of causal basis for the phenomena. This conclusion follows first from the fact that the series result from the growth of the organism, and second from the cer- tainty, at least in many cases, that the continuance of life of the individual involves the maintenance of the series, this in turn involving some measure of metabolic interdepen- dence among the members of the series. Attempted Causal Explanation of These Series For establishing the general truth of this type of inte- gration we need not, in strictness, go any further than we have gone. Nevertheless, the importance of the subject justifies a few remarks on attempts that have been made to explain the series causally. The best known of these comes from botanists, and conceives that the diminishing series of leaves and other structures, seen with more or less distinct- ness almost universally among plants, is due to the increas- ing remoteness of the successive parts from the roots of the plant, that is, from the main source of the plant's food. It is obvious, however, that this explanation is not of general application, since in animals the food does not come from a root system which anchors the organism to its food-yielding medium. Nor is it possible to bring the series in all animals into correlation with a blood circulatory system, as their existence in many coelenterates, hydroids and alcyonarians Growth Integration 105 for, example, where no circulation exists, shows. It is al- most certain, too, that the series occur in many plants that have no sap system such as is assumed by the physiological explanation above indicated. Many of the marine algae come under this head, a striking example of which is the kelp Macrocystis pyrifera of the western coast of both Americas. That the laminae of this plant fall into a beautiful direct gradient series is a fact which can not escape the notice of any one who sees them. The question of whether each streamer of laminae reaches finally and necessarily a limit of growth in which the size series is present is not so certain, but from considerable attention to the question I am almost sure this is the case, although the point needs more study. Another interesting and probably useful course of reason- ing about organic growth attempts to connect the results of growth with autocatalytic chemical action. Although these attempts have not, so far as I am aware, taken special cog- nizance of the natural size series which are occupying us, but have been concerned with the weights or volumes of or- ganisms at various stages of growth, there is little doubt that the phenomena we have been considering are closely connected with those dealt with in these attempts. T. Brails- ford Robertson seems to have devoted more thought to this matter than any one else. The following, taken from the summary of conclusions found in his original paper, pre- sents the most essential parts of his theory: "(1) In any particular cycle of growth of an organism or of a particular tissue or organ of an organism the maximum increase in vol- ume or in weight in a unit of time occurs when the total growth due to the cycle is half completed. (2) Any particu- x lar cycle of growth obeys the formula log K(t-ti), A — x where x is the amount (in weight or volume) of growth which has been attained in time t, A is the total amount of growth attained during the cycle, K is a constant, and t^ is 106 The Unity of the Organism the time at which growth is half completed." Assuming that the growth of an amphioxus, let us say, to adulthood represents a growth cycle of this statement, that the production of somites begins with the most anterior one and proceeds toward the tail, and that the successive growth- increments (corresponding to x in the formula) are regis- tered in the somites as we find them, then the animal's body as exhibited by its myomercs would correspond fairly well to Robertson's statement under (1), as would several of the other growth series we have glanced at, and as would also great numbers of series presented by ordinary plants and animals. The formula for growth contained in (2) is, according to Robertson, usuch as would be expected to hold good were growth the expression of an autocatalytic chemical reac- tion." Assuming the general correctness of these state- ments, no one interested in the larger problems of organic growth could hesitate to believe that they must be impor- tant in some way. However, that the relations shown do not prove that au- tocatalytic chemical activity is a cause of growth in any- thing more than a subordinate, contributory way, is obvious on reflection. In the first place, Robertson himself has pointed out, in substance, that such action says nothing about the particular shape which the mass of transformed substance takes, but since some characteristic configuration or shape is fundamental to all organic growth, the entities for which A and x stand in the formula are really only ab- stractions. Although the formula may apply approximately to a great many organisms, it will apply to none exactly, except by chance to a very occasional one. This is the gen- eral form of criticism, illustrations of which are seen in the fact that in the series of direct and inverse gradients shown in the vetch (figure 59) and Cassia (figure 60), respectively, the formula appears not to apply at all. The general pur- Growth Integration 107 port of the strictures here placed upon the value of this explanation of growth is well brought out by Moeser, who says, probably with literal truthfulness, "One will not find two germinating plants (Keimpflanzen) which would have exactly the same growth curve, even though they proceed from seed of absolutely the same weight and grow under */ o o exactly the came conditions." 4 The kernel of this criticism is that even though it should be established, as very likely it will be, that autocatalytic action is an essential factor in all growth, it can be a causal explanation in only a partial and subordinate sense. This is so because although K is a constant for a particular indi- vidual as observed, it assumes different values for different groups, partly at least because no account is taken of size or configuration. Moreover, even if these factors were con- sidered, there would be nothing corresponding to a physical constant (depending only on autocatalytic action), since one of the most distinctive things about organic growth is that it is differential, the differentials corresponding to the taxonomic group to which the individuals belong. Even though we are still much in the dark as to what the causal nexus is between the growth processes and the quan- titatively graded series so widely seen in nature, it seems certain that some such nexus exists, and that its operation constitutes a true integrational factor in the individual. It appears, too, that this type of integration is about the simplest and that it accompanies the simplest type of dif- ferentiation, the two together constituting the simplest type of organization above the organization of the cell. But into this interesting subject we can not now go. Axial Metabolic Gradients as Integrative Phenomena For the most thorough and sustained experimental inves- tigation of the primary integrative processes in growing 108 The Unity of the Organism organisms that has been made, biology is indebted to C. M. Child. In two recent volumes he has summed up and sys- tematized the elaborate researches prosecuted by him in this field almost exclusively for fifteen years, and has presented his conclusions more fully than in any of his previous writ- ings. The limitation set for the present to the constructive part of our enterprise makes it impossible to do more than touch at a few points the great mass of experimental evidence on which Doctor Child bases his conclusions. Fortunately, however, the kernel of the conclusions can be stated rather clearly in a small space. Although (surprisingly, it seems to me) Child refers hardly at all to the graded meristic series occurring in na- ture, to which the preceding pages have been devoted, it can hardly be doubted that the phenomena with which he deals, and calls "axial gradients," come under the same head as do those which have been occupying us. The phenomena which in the first instance Child has been concerned with, have been brought to light mainly through studies on re- generation in many lower animals. But the general con- clusions reached are far broader than this ; indeed they ex- tend to well-nigh the whole scope of organic growth, but especially to growth which involves elongation either of the whole organism or of certain parts of organisms. Thus the head-tail type of individual, whether the body be segmented as in arthropods and in many worms, or unsegmented as in other worms and in molluscs, is perhaps the most striking exemplification of the axial gradations with which Child deals. The following quotation shows the generality with which he views the matter from the ontogenic side: "Gra- dients in rate of cell division, size of cells, condition or amount of protoplasm in the cells, rate of growth, and rate and sequence of differentiation are very characteristic fea- tures of both animal and plant development. Such gra- Growth Integration 109 dients are definitely related to the axes of the individual or its parts, and are evidently expressions of axial metabolic gradients. While the existence of such gradients indicates the existence of gradients in activity of some sort, the various kinds of gradients are not all necessarily pres- ent where metabolic gradients exist. In some cases the vis- ible gradient may be a gradient in rate of growth or in protoplasmic constitution ; in still others a gradient in sequence of differentiation, etc., and sometimes metabolic gradients exist without any structural indications of their presence. At best these various kinds of gradients are merely general indications of differences in metabolic rate and undoubtedly in many cases the visible differences along an axis represent something more than differences in meta- bolic rate. The important point is that visible indications of graded differences in metabolic rate occur so generally in definite relations to the chief axes of the bodv.;> * ' One phase of this general statement is the developmental correlation that various regions of the bodv in many lower ^j •. *s animals have with the head or anterior end, these regions being developmentallv dominated, in Child's expression, by the anterior end proportionally to the distance of the re- gion from the end. A typical case is furnished by flat-worms of the genus Planaria, animals especially favorable for experiments in regeneration, since they are very hardy to laboratory con- ditions and have great powers of reconstituting themselves from pieces of various sizes, shapes and positions cut from them. "Any piece of the planarian body," says Child, "is capable of giving rise to all parts posterior to its own level, whether a head is present or not, but no piece is capable of producing any part characteristic of more anterior levels than itself, unless a head begins to form first." From a great mass of experimental evidence produced by Child and others we have the following: "These facts force 110 The Unity of the Organism us to the conclusion that in such experimental reproductions there is a relation of dominance and subordination of parts. The apical or head region develops independently of other parts but controls or dominates their development, and in general any level of the body dominates more posterior or basal levels and is dominated by more anterior or apical levels." 7 A really unique merit in Child's work is the fact that he has given special attention to the connection of these axial gradients manifesting themselves in various structural and functional ways, with the fundamental metabolism of the organism. Several methods of experimenting have been em- ployed to this end, the one most frequently used being what he calls the susceptibility or survival-time method. The es- sence of this depends upon the fact, determined by many ob- servers, "that a relation exists between the general meta- bolic condition of organisms, or their parts, and their sus- ceptibility to a very large number of substances which act as poisons, i.e., which in one way or another make meta- bolism impossible, and that difference in susceptibility may be used with certain precautions and within certain limits as a means of distinguishing differences in metabolic condition, and more specifically, differences in metabolic rate." The demonstration of metabolic gradients by this method depends upon the fact that "death and disintegration of dif- ferent parts of the body usually follow a regular sequence," this making it possible "to determine the time, not merely of disintegration of the whole animal, but of the various re- gions of the body." Another way of showing difference in rate of metabolism in different parts of the organism is by the use of the biom- eter, an apparatus for estimating minute quantities of carbon dioxide, recently devised by S. Tashiro in connection with his important researches on carbon dioxide production in nerves. By these methods it is shown, pointing to a single Growth Integration 111 instance, that in pieces of a flat-worm isolated by cutting "the rate of metabolism is higher in long anterior pieces than in posterior pieces of the same length." Starting from this low but seemingly universal level of integrative phenomena in the individual, Child formulates views of the nature of organisms that agree very well with the organismal standpoint upheld in this volume. He writes : "The organic individual appears to be a unity of some sort. Its individuality consists primarily in this unity, and the process of individuation is the progress of integra- tion of a mere aggregation into such a unity, for this unity is not simply the unity of a chance aggregation, but one of a very particular kind and highly constant character for each kind of individual. In all except the simplest individ- uals it determines a remarkable degree of uniformity and consistency, both in the special relations of parts and the order of their appearance in time, and also in coordination or harmony of functional relation to these parts after their development." M eristic Gradients and Metabolic Gradients Both Phenomena of Growth Integration In view, then, of the exceedingly wide prevalence in living nature of axially disposed meristic series quantitively graded, and of the equally wide or even wider prevalence of axial gradients on the basis of metabolic activity, the gradients of both sorts arising as fundamental growth phe- nomena, it appears impossible to avoid recognizing our first category of integration, namely, growth integration, as about the most simple and primal and universal of all these categories, at least for multicellular organisms. It seems as though the other kinds of differentiation and integration are superposed, as one might express it, upon this primordial kind. To a consideration of the other, superimposed inte- The Unity of the Organism grations we now pass, taking them again in their seeming order of obviousness. REFERENCE INDEX 1. Torrey 139 7. Child (1) 215 2. Ritter ('09) 71 8. Child (1) 66 S.Robertson 612 9. Child (1) 77 4. Moeser 373 10. Child (1) 73 5. Child (2) 65 11. Child (2) 2 6. Child (1) 213 Chapter XVIII » CHEMICO-FUNCTIONAL INTEGRATION Functional as Contrasted with Growth Integration A SSUMING Child's theory of metabolic gradients to be •*• *-well grounded, we are furnished thereby with one im- portant insight into the chemical processes involved in the unity of the individual organism. But that process is con- cerned primarily with the growth, with the production of the individual. The question now is, are there chemical proc- esses the object of which is to maintain the functional unity of the complete or nearly complete individual? Are there chemical operations the office of which is to preserve a proper interrelation among the parts of the organism as these perform their special offices? That such is to some extent the significance of most if not all internal secretions as usuallv understood is indicated •> by the fact that the functional disturbances attending re- moval of the thyroids or other glands from various animals ; and by the further fact that where internal secretions play a part in development, their action is rather that of stimula- tor, or at least modifier, than of true producer. The conception of internal secretions as being at least as much regulators of physiological function as of growth is illustrated by cases of hypopituitarism of the post- adolescent type, like those described by Gushing, for ex- ample. In the series of cases of disease due to "pituitary deficiency" the first symptoms appeared when the subjects were from thirty to forty years old. 113 114 The Unity of the Organism The Conception of "Internal Secretions" The nature of the phenomena now to be considered, and their significance for our discussion make it desirable to think about these secretions from the broad standpoint first stated, according to Bayliss, by Brown-Sequard and d'Arson- val, namely, as materials produced by any living cells or tissues which are discharged into the blood or lymph and have specific effects on other parts or functions of the or- ganism. Regarded thus it is now known that many cells of the organism produce internal secretions. Although we are more concerned with function than with structure in this discussion, our purpose will be best served by beginning with a morphological classification of the secretion-pro- ducing cells. They may be divided into tAVo categories, those which are disposed into definite organs, or glands, the ductless glands of long standing in anatomy ; and those which are not assembled in such organs. Knowledge of this second class of cells is of recent date,, and is fuller from the functional than from the structural standpoint. The chief glands, to which the name Endocrine has lately been given by Schafer, are now so well known as hardly to need men- tion. They are the thyroid apparatus, including the thy- roids and the parathyroids, the suprarenal body, the pitui- tary body, and probably the thymus and pineal bodies. Cells now known to produce internal secretions but which are not arranged in glands are certain cells of the pancreas scat- tered among the pancreatic cells proper ; certain cells of the alimentary mucous membrane; the interstitial cells of the ovary and of the tcstis, and probably certain cells of the placenta, of the mammary gland, and of the uterus. Following our usual course of making the treatment merely illustrative rather than aiming at exhaustiveness, our selection will include one example from each of these groups. From the glandular category we take the thyroid Chemico-Functional Integration 115 apparatus, and from the non-glandular a portion of the alimentary mucous membrane, namely, that of the duo- denum. Effects of Removing tlie Human Thyroid for Curative Purposes As definite knowledge of the great physiological impor- tance of internal secretions begins with human surgery- with operations on the thyroid apparatus — we may well begin our study here. This is the better starting point in that there is no more striking illustration of how great a part of the whole organism may be implicated in the action of internal secretions than is afforded by the prod- ucts of the thyroids and parathyroids. The subject first came into clear light in the early eighties of the last century through the experiences of Swiss sur- geons, Theodor Kocher and J. L. Reverdin especially, who removed the thyroids to cure goitre, this disease being spe- cially prevalent in some parts of Switzerland. The patients operated on were found to improve rapidly for a time after the operation, but later untoward symptoms began to mani- fest themselves. Because the variety and pervasiveness of these symptoms in a typical case are highly instructive for us we present them in detail, selecting a description from Human Physiology by Luciani : "Patients who have under- gone total thyroidectomy . . . experience the initial symp- toms of glandular deficiency either at once or at latest some weeks after the operation. They feel weak, complain of heaviness of the limbs, and more or less diffuse dull pains, particularly in the legs, which may become acute and assume the character of pains in the bones. "Other more serious symptoms are gradually associated with the preceding. After four or five months the face and the extremities swell and become cold, the muscles are 116 The Unity of the Organism torpid, sometimes rigid, often exhibiting muscular tremors, and are incapable of carrying out any delicate manual acts of precision. At first the swelling is variable ; it is more pronounced in the morning than in the evening, but steadily increases until it becomes permanent. It is not ordinary cedema, in which percussion with the fingers leaves a depres- sion ; it Js a hard and elastic swelling. It is specially local- ized in the hands, feet and face, where it produces a char- acteristic alteration of the countenance. The lower eyelids are the first to present a sacculated, semi-transparent swell- ing, which is hard to the touch ; then the infiltration spreads to the folds of the face, wrhich become smoothed out ; to the nose, which gets rounded ; to the lips which swell, and bulge outward, saliva dribbling from them. The features are coarsened and expressionless like those of a cretin. "The mental functions accord with this appearance, since they are blunted, so that the patients lose their memory, become deaf, taciturn, melancholy, self-absorbed, and reply extremely slowly to questions. They further complain of slight but perpetual headache ; feel an almost constant sen- sation of cold, which is most acute at the extremities ; at times they are seized with vertigo, and may even lose con- sciousness. "All the symptoms become still further aggravated. The whole body may grow more bulky from the extension of the swelling. The skin loses its elasticity, can only be picked up in large folds, and becomes dry owing to defective capacity for sweating. The epidermis desquamates in more or less extensive lamellae, particularly on the hands and feet ; the hair turns grey, falls out, and gets constantly thinner. "The heart functions weakly, but with ordinary rhythm ; the pulse is small and thready. Examination of the blood shows nothing constant ; but there is often a more or less pronounced and progressive oligocythaemia, which undoubt- edly contributes to the characteristic pallor of the skin, Chemico-Functional Integration 117 this being of the earthy, yellow-spotted hue peculiar to cretins. "The respiratory rhythm is almost always normal ; the digestive apparatus functions well, as also the urinary system. The spleen is not enlarged." This complex (syndrome in medical terminology) of manifestations is known technically as cacliexia tliyreo- priva. Later experience by other surgeons with the same opera- tion discovered that in some cases the effects are much more acute and rapid, and may be replaced by what has been called "tetany" (though having little in common with ordi- nary tetanus), ending in death more often than otherwise. Experimental Thyroid Excision in Normal Lower Animals No sooner had the far-reaching influence of the thyroid for the human organism begun to be recognized in this way than experimentation on inferior mammals was invoked for further light on the subject. Moritz Schiff, the ground- breaker in this field, published in 188-t the results of the removal of the thyroid from a large number of dogs. In all cases where the whole thyroid apparatus was excised the dogs soon died after a run of such symptoms as tremor, spasms, and convulsions. Nor did Schiff rest content with merely ascertaining the effects of removal, complete and partial, of the thyroid apparatus. He found that these effects could be entirely prevented by grafting a portion of the gland under the skin or into the body cavity of the animal before the thyroid operation, or by injecting thyroid juice into the blood or lymphatic systems, or by feeding raw thyroid to the dogs. The story of how these experiments led to the now widely practiced treatment of myxoedema with thyroid or thyroid extract would be out of place here, though it should not be passed wholly unnoticed. 118 The Unity of the Organism So an enormous mass of evidence, experimental, surgical and clinical, is now in court demonstrating1 that for some o animals at least, among them being the human and the canine species, products of the thyroid apparatus are in- dispensable to the normal life, the symmetrical growth and balanced physiological activities of the organism. That the apparatus is essential to the "Hormonic Equilibrium" of the organism in some animals is beyond question. While no pretense can be made at an exhaustive exami- nation of this evidence two phases of our discussion make it desirable to cary the examination on the manifestational side a little farther. One of these is the importance of making as objective and emphatic as possible the extent of the manifestations in the individual ; the other is the ques- tion of the generality, taxonomically speaking, of the thy- roid apparatus. In the interest of the first of these I present, verbatim, the report of a single case of complete thyroidectomy, the animal in this instance being a fox. The individual concerned was a female less than one year old. "Oct. 28. Glands removed; good recovery. "Oct. 29- Normal., but does not eat. "Oct. 30. Salivation, rapid breathing, strong tremors and tet- any from 7 A. M. to 2P.M.; quiescent but weak during the rest of the afternoon. "Nov. 1. Normal, but rather weak; eats; no sign of tremors or salivation during the day. "Nov. 2. Restless; slight tremors; dyspnoea; does not eat. "Nov. 3. Some depression, but no tremors or salivation until 4 P. M. ; does not eat. At 4 P. M. spasms appeared and con- tinued unabated as long as observed (7 P. M.). "Nov. 4. Found dead at 4- A. M. Post-mortem examination revealed no parathyroids nor accessory thyroids." As to taxonomic range and character of manifestation of thy- roid influence, much diversity might have been anticipated on general natural history grounds. As far as investigations have gone they realize these anticipations. A summary of results will serve our purpose, and this is at hand in Schafer's volume already Chemico-Functional Integration 119 cited. Concerning the effects of removal of the thyroid appa- ratus he says : "The most acute symptoms are exhibited by carnivora such as dogs, cats,, foxes, and wolves (Vincent), and the young of herbi- vora (v. Eiselsberg, Sutherland Simpson) and are of a nervous nature. . . . Some species exhibit no symptoms whatever — at least when the operation is performed on the adult. Horsley states that this is the case with birds and rabbits; but according to Gley, the latter are affected if care is taken to find and re- move all four parathyroids, and Doyon and Jouty obtained typical tetany in hens which had been parathyroidectomized. . . . Ac- cording to Vincent and Jolly badgers are totally unaffected by complete removal of both thyroids and parathyroids." From the anatomical characteristics of the organs, and from the known effectiveness of minute portions of them, such statements as the last must be taken with re- serve. Although these results show by their diversity that an enormous amount of study remains to be done on the comparative side, they leave no question that the secretion of the thyroid apparatus is important for the general health and equilibrium of most animals in which it occurs. The measure of this importance in the eyes of some authori- ties is seen in such a statement as, "No cell anywhere in the body can reach morphological perfection without thyroid stimulus." 4 The Internal Secretion of the Duodenal Mucous Membrane We now pass to an examination of the effects of the internal secretion of the duodenal mucous membrane. This particular secretion is selected for the reasons that it is, according to Bayliss, one of its discoverers, "the most typical of all the chemical messengers"; that it was one of the first to be investigated ; and that it is one of the few which have been isolated as definite substances. 120 The Unity of the Organism The mode of operation of this secretion is tersely stated by Bayliss : "Food entering the duodenum causes the pro- duction of a special substance which enters the blood and excites the pancreas to pour into the duodenum a digestive juice." 5 That the presence of various substances, especially acids, in the duodenum, induces a flow of pancreatic juice was known when Bayliss and Starling began their work in this field ; but up to that time the excitation of the pancreas to such action was supposed to be through a nerve reflex. These investigators had reported in 1902 6 that acid in the duodenum is able to cause the pancreas to secrete after nervous communication between the intestinal wall and the pancreas is excluded. They went further and obtained an extract from the duodenal mucous membrane which, being injected into a vein, induced a copious flow of pancreatic juice. The substance, whatever it is, which acts thus they call secretm. It has been surmised by a few physiologists that the effects are not due to the direct action of the secre- tion on the pancreatic gland-cells, but that the influence is exerted through the vaso-dilator mechanism. But this surmise is negatived by the demonstration that the secretin will induce the flow of pancreatic juice while it does not alter the blood pressure. The case seems, then, fully estab- lished, and is so clear-cut and relatively simple an instance of the coordinated functioning of two wholly distinct parts of the body through chemical means, that it is desirable to get sharply before us the known steps in the process. In the course of normal digestion, food acidulated in the stomach passes into the duodenum. Here, probably in virtue of its acidity, it acts upon the cells of the mucous membrane in such a way as to induce them to produce a substance which is discharged, not into the intestines, there to take its part in digestion, but into the blood. By the blood stream the substance is carried through its whole Chemico-Functional Integration circuit, hence through the lungs and so on, around to the pancreas, the typical gland-cells of which it excites into activity, so that the pancreatic juice, an "external" instead of an "internal" secretion, is poured into the duodenum to exercise its digestive office on the same food which started the cycle of activities. It was with this substance particularly before their minds that the authors adopted the name hormone to designate substances which act thus. "The group of substances re- ferred to," says Bayliss, "which includes adrenaline and the various internal secretions, is characterized by the prop- erty of serving as chemical messengers, by which the activity of certain organs is coordinated with that of others. They enable a chemical correlation of the functions of the organ- ism to be brought about through the blood, side by side with that which is the function of the nervous system." 7 This reference to the side-by-side activities of chemical messengers and nervous system in integrating the organism touches a subject of the utmost importance. Considera- tion of it must, however, be deferred until we have looked a little more into the nature of hormones. The Nature of the Active Substances in Internal Secretions That the peculiar iodine-rich albuminous substance ob- tained from the thvroid by Baumann in 1895 and since *< »/ observed by other investigators, contributes in some essen- tial way to the action of the secretion of this gland is the belief of apparently a large majority of authors (Bayliss, Eppinger, Howell, etc.), but not of all (Luciani). In view of the uncertainty on the point Schafer's proposal "to ex- press our ignorance by a term which implies no theory" may well be accepted, with the proviso that the term pro- posed be really taken as evidence that something though not everything is known about the substance. A part of The Unity of the Organism the proposal is worth quoting. "I propose therefore pro- visionally to apply the word thyrine to denote the active principle, whether it be identical with or contained in the iodothyrin of Baumann or not." Thyrine then becomes the name of a substance the source and some of the activities of which are known, but whose main physical and chemical attributes are unknown. Concerning the mode of action of thyrine there are sev- eral divergent views, all based on some evidence and so perhaps not entirely antagonistic. Is the antitoxic theory of Luciani £ partly right, right as regards the parathyroid secretion (Moussu, Vassale and Generali), and partly wrong, wrong as to the secretion of the thyroid proper, this being trophic rather than antitoxic? ] May there not be more in the enzymic theory suggested some years ago, than later writings have been inclined to favor? Does the fact that internal secretions seem to be simpler than enzymes, as indicated by their greater resistance to heat, preclude the possibility that their normal mode of action is of the enzyme type after all? That is, may it not be necessary to extend the conception of enzymic action (which is surely generic anyway) to include the various sorts of activity presented by hormones, understood in the sense given it by its origi- nators? But neither can the resemblance of internal secretions to drugs, so far as their action is concerned, be overlooked. This has been dwelt upon by Schafer 5 and has important bearings on the problems of the origin as well as on the chemical nature of the substances. Another aspect of the mode of action of internal secre- tions is that of whether the effects are to stimulate or inhibit the activity of the organ or tissue on which they operate. Schafer and others make a special point of this, directing the attention to the fact, by way of illustration, that the adrenaline of the suprarenal medulla causes contraction of Chemico-Functional Integration the plain muscle of the blood vessels and inhibition of that of the intestines.12 The distinction has an undoubted natu- ral grounding, and so is in the interest of accurate descrip- tion and clear conception. As to the actual chemical composition of internal secre- tions, knowledge is exceedingly meager. More is known about adrenaline, the active principle of the suprarenal gland, than about that of the secretion of any other gland or tissue. This was isolated by the Japanese chemist Jokichi Takamine in 1901, and has since been more fully examined by several investigators, notably by T. B. Aldrich. It is described as a micro-crystalline substance occurring in at least five crystal forms. Aldrich assigns to it the em- pirical formula C9Hir,NO;], this structure placing it not far from tyrosin in the benzene or aromatic series. Of special interest is the astonishingly minute quantites which produce physiological effects. According to Aldrich 0.000001 gram of an aqueous solution of the chloride per kilo of body weight injected into the blood system raises the blood pres- sure 14 mm. of mercury.1; The chemical nature of Tetlielin, lately isolated from the anterior lobe of the pituitary of the ox, has been studied by its discoverer, Robertson. It is described as white or pale cream colored, readily powdered, highly deliquescent, and having a greasy odor and slightly acid reaction in aqueous solutions. It contains 1.4 per cent of phosphorus and four atoms of nitrogen for every atom of phosphorus. The phosphorus-nitrogen content of the substance is con- sidered by Robertson as specially significant, since this seems to ally it chemically with "phytin," a substance found in the rapidly growing parts of plants, and in milk. The natural suggestion is that the growth-promoting substances in plants, milk, and the pituitary secretion are chemically related. The Unity of the Organism The Close Resemblances and Interrelations of the Different Internal Secretions Even the meager, merely illustrative examination of in- ternal secretions we have been able to make brings out the close resemblance there is between the several endocrine glands, and also between the physiological effects of the various secretions. These resemblances suggest an intimate organic interrelationship among all the internal secretion- producing parts of the body. All investigators in this field, no matter to how restricted a section of it their efforts are primarily directed, seem to come upon the interdependence of the sources and activities of hormones. To illustrate, Gushing, whose central interest has been the hyphophysis, is led to conclude that experi- mentally induced hyphophyseal deficiency works histologi- cal changes in many if not all the other ductless glands. It is not surprising, consequently that far-reaching theories have been elaborated on the basis of these relationships. Bayliss refers with approval to Elliott for the conserva- tism with which he sums up the present state of knowledge on this aspect of the general subject. But even so, features are pointed out "which suggest a common bond" : "(1) Carbohydrate metabolism is influenced, not only by the pancreas, but also by the thyroid in super-activity, in acromegaly, and by the injection of adrenaline. "(2) Growth is affected by the testis and the cortex of the suprarenals, arrested by the absence of the thyroid. "(3) Nervous implications. "(4) The pituitary becomes hypertrophied when the thy- roid is removed. Acromegaly may lead to enlargement of the thyroid."14 At the other extreme of what may be regarded as legiti- mate scientific theorizing, we have the views of Sajous, who believes research will finally demonstrate a relationship be- Chemico-Functional Integration tween all the ductless glands the combined functioning of which dominates most of the activities, normal and patho- logical, of the organism. Sajous' elaborately worked-out theories of internal se- cretions, especially in their relation to disease and medical practice, are opposed at many points to prevailing opinion based on present day research. Nevertheless regarded from the standpoint of general biology there would seem to be much merit in his effort on the one hand to find a common ground in the metabolic processes for all the phenomena at- tributed to endocrinal activity ; and on the other hand to find a more consistent morphological and physiological basis of definition and classification of internal secretions and the structures which produce them than has yet been recognized. For example, whether Sajous is right or not in contending that the pituitary body does not produce an internal secre- tion, certain it is that the non-glandular structure of its posterior part, extracts of which alone have slowing effects on the heart, is strongly suggestive to the critical naturalist that the inclusion without qualification of this part at least of the organ among the endocrine glands is an instance of what is known to taxonomists as "lumping" in classification -a kind of practice that advance in knowledge always finds to be inadequate for purposes that are critical. Sajous' late summary of his views is highly suggestive to the general biologist, even though it is excessively theoretical in some parts. As far as a much interested outsider can judge, the pres- ent state of understanding of the relationships among the internal secretions is set forth with exceptional judiciousness by Waller. "There can be little doubt," the author opens his discussion by remarking, "that the various internal secre- tions are most closely correlated, yet perhaps the most dif- ficult, and also the most fascinating problem of present day medicine, is to assign to each its proper and right share of 126 The Unity of the Organism importance." 15 This statement, coupled with the fact that one of the main objects of the discussion is to display the many contradictions which the author's large experience as a practitioner has found in the action of the internal se- cretions, is about the most striking, and from our stand- point most significant thing about this paper. As one illustration of the agreement of action of the se- cretions, or at least of the influence of the endocrine glands, it is pointed out that changes in calcium metabolism have been observed after removal of the thymus ; in disease of the pituitary and of the pineal bodies ; after castration ; after ovariotomy ; after removal of the suprarenals, and after re- moval of the thyroids and parathyroids. Of the numerous instances of contradiction which he brings out, we mention only that concerning tetany. This he shows may result from either removal of the thyroid or from an overdose of thyroid extract. The explanation of the contradictions in the action of a given secretion favored by the author is that of the "varying influence of the other internal secretions." But the descriptions given seem to leave no doubt that difference in type of individuals also comes into the explanation. Thus among children afflicted with enlarged tonsils and adenoids, the two distinct types dependent upon the character of the symptoms, is a case in point. One type is dull and stupid, stunted in growth, has dry coarse skin, and may display symptoms of rickets. The other type is vivacious physically and mentally, given to peevishness, irritability and quick fatigue, and always want- ing a change of activity. This type is over-tall for its age, perspires readily and is fine-skinned. Both types of cases are benefited at least for a time, Waller says, by treatment with thyroid extract. Concerning the general nature of the interdependence among internal secretions, this author's views seem to me so eminently sound that I cannot refrain from quoting them in Chemico-Functional Integration some fullness : "Considerable stress has been laid upon the antagonism of different internal secretions by various au- thors. I believe we should gain a truer insight into their working if we dwelt rather upon their harmony. It does not strike me as a very high conception of the human organism that health should consist in the balance of dissentient or antagonistic forces. It would seem far more ideal that all the internal secretions should work together for the common good of the organism, and that when some special demand is made upon a particular gland the others will work in har- mony with it. Every gland is probably necessary for the perfect activity of the rest, and the harmony between the glands is demonstrated by physiological experiments. . . . When it is found that the removal of an organ constantly induces either atrophy or hypertrophy of some other organ, we can reasonably deduce that in the first case the organ removed is essential to the welfare of the one that atrophies in its absence, and in the second case that the hypertrophying organ is endeavoring to replace the lost one, in some de- gree, and that therefore the two organs have a kindred function." 16 As an example of the first case, the fact is cited that the removal of the thyroid or of the anterior part of the pitui- tary induces the atrophy of the testicles or the ovaries. The second case is illustrated by the hypertrophy of the supra- renal from the removal of the thyroids, and also by the hypertrophy of either the thyroid or the pituitary on re- moval of the other. "The demonstrated facts of hyper- trophy," we read, "clearly point to an entente or even a triple alliance between thyroid, hypophysis and suprarenals. And the genital system is absolutely dependent upon the integrity of these three." 1T Stating now, in a single paragraph, the results of inves- tigations in this field, we have : The different parts and ac- tivities of the organism are maintained in their normal state, 128 The Unity of the Organism both as to the essential nature of each, considered individ- ually, and as to their relation with one another, by a number of exceedingly powerful and subtle chemical substances (in- ternal secretions) which are produced by certain parts, are passed into the blood, and by it are carried about over the whole organism to exert their appropriate influences on other parts and functions. Because of the peculiar way these substances do their work, they have been called chemical messengers, or to have a distinctive name, hormones. Relation Between the Internal Secretory and Nervous Systems But no physiological truth is better known than that one of the main offices of the nervous system is to correlate the organs and parts of the body with one another. It is but natural to suppose, therefore, that if there is a chemical scheme for accomplishing the same end, the two are in some way closely related. That the relations which exist between the cerebro-spinal nervous system, the autonomic nervous system (including the sympathetic), and the internal secretions, constitute one of the most important subjects in the whole physiological do- main, at the same time that it is one of the most recondite and difficult to investigate, has come gradually to view through the work of the last few decades. We will try to extract enough from the mass that has been written on the subject, to illustrate the principles involved. The modern period of knowledge of what was formerly but rather in- definitely included under the term sympathetic nervous sys- tem, has revealed that we have to do with a portion of the general nervous mechanism which in reality is a subdivision of a larger category. Chemico-Functional Integration 129 Composition and Nature of tlie Autonomic System The name autonomic was given to this category by Lang- ley. "The autonomic nervous system," he says, "means the nervous system of the glands and of the involuntary muscles ; it governs the 'organic' functions of the body" ; and further : "The word implies a certain degree of independent action, but exercised under the control of a higher power." Bay- liss adds: "It is necessary to be quite clear that the au- tonomic system includes the sympathetic, since some writers abroad use the name as applying to all the visceral nervous system other than the sympathetic, speaking of sympathetic and autonomic." Perhaps the most important single fact which differen- tiates the autonomic from the cerebro-spinal system is the intercalation, everywhere in the autonomic system, of an extra neurone between the cerebro-spinal nerve and the part innervated. Cannon states this distinction very clearly: "The skeletal muscles receive their nerve supply direct from the central nervous system, i. e., the nerve fibers distributed to these muscles are parts of the neurones whose cell-bodies lie within the brain or spinal cord. The glands and smooth muscles of the viscera, on the contrary, are, so far as is now known, never innervated directly from the central nervous J system. The neurones reaching out from the brain or spinal cord never come into immediate relation with the gland or smooth muscle cells ; there are always interposed between the cerebrospinal neurones and the visceral extra neurones whose bodies lie wholly outside the central nervous system." 20 Cannon's suggestion that these interposed neurones may function as transformers for impulses received from the cere- brospinal system should be noted here. Three sharp subdivisions of the autonomic nervous sys- tem are recognizable. One is known as the vagal or cranial 130 The Unity of the Organism autonomic, because it is largely made up of fibers from the vagus, or tenth pair of cranial nerves. Another is the sym- pathetic, or better, the thoracico-lumbar autonomic, be- cause its fibers originate from the great visceral sympathetic ganglia. This is by far the most extensive of the three sub- divisions, and is the only one that is distributed to all parts of the body. The third is the sacral autonomic. As its name implies, it is quite restricted in extent, its fibers being dis- tributed to the extreme distal end of the intestine, the urin- ary bladder, and some of the external genital organs. But the differences between the three which are most important for us are physiological, a particularly important difference being that the thoracico-lumbar division acts antagonistic- ally to both the end divisions. Stimulation of the fibers of the sympathetic has just the opposite effect to the same stimulus applied to the fibers of the others. "The sympa- thetic fibers check, the vagal autonomic fibers excite, the movements of the intestines ; the sympathetic dilates, the vagal autonomic contracts, the pupil ; the sympathetic hastens, the vagal autonomic slows, the heart." 21 The sacral contracts the lower part of the large intestine and re- laxes the outlet of the bladder, while the sympathetic relaxes the same part of the intestine and contracts the same part of the bladder. Cannon states the general principle thus : "When the mid-part meets either end part in any viscus their effects are antagonistic" While the incompleteness of knowledge in this field needs emphasizing, yet that knowledge is sufficient to put some of the main features beyond question, and to make clear the great importance of the subject and of fuller knowledge on it. Touching these general aspects Professor L. F. Barker writes : "While we do not yet understand the exact mechan- isms of association among the activities of the cerebrum, the endocrine glands, and the reciprocally antagonistic au- tonomic domains and their end-organs, we can begin to see Chemico-Functional Integration 131 the paths which must be followed in order that more exact knowledge may be gained." Experimental Evidence of Connection Between the Adrenal Glands and the Nervous System Some of the most important information we have in this field is furnished by Cannon and his collaborators concern- ing the secretion of the adrenals and its relation to the autonomic and central nervous systems. It had been proved before Cannon began his investigations that adrenin injected into the blood has exactly the same effect on certain parts of the organism as does the sympathetic autonomic nerves with which the same parts are supplied, and that the effect of the secretion is direct and not through the nerves. In other words, it had been proved that the organism has two methods by which the same activity of certain of its parts can be induced, one nervous, the other chemical. Thus the dilation of the pupils, the erection of hairs, the inhibition of activities of the alimentary canal, and the liberation of sugar from the liver can be induced either through sym- pathetic autonomic centers or by the secretion of the adrenal bodies. This in itself was important evidence of interrela- tion between the nervous system and internal secretory sys- tem. But the experimental researches prosecuted in Can- non's laboratory have proved that a connection exists be- tween the autonomic-adrenal phenomena and the cerebro- spinal system through the sensory nerves, and with the psychic life of the animal ; and have shown the probable sig- nificance of the entire scheme for the life of the organism as a whole. To be a little more specific, they have proved : (1) That strong excitation of sensory nerves stimulates reflexly the adrenal glands and causes them to pour an increased amount of adrenin into the blood. 132 The Unity of the Organism That emotional excitement (as the fright of a cat by a dog) similarly increases the flow of adrenin. (3) That this increase of adrenin in the blood may in- crease the liberation of sugar from the liver into the blood to such an extent as to make sugar appear in the urine, thus demonstrating a true "emotional glycosuria." (4) That the increased adrenin of the blood thus pro- duced is probably advantageous to the organism in that it enhances its ability to meet special stresses that naturally accompany special excitement, as of fear, anger, or pain, this advantage consisting partly in augmentation of the working energy of the muscles, probably through the sugar delivered to them, and in increasing the coagulability of the blood, thereby reducing the danger from bleeding wounds. Summing up his conclusions as to utility, Cannon writes : "These changes in the body are, each one of them, directly serviceable in making the organism more efficient in the struggle which fear or rage or pain may involve; for fear and rage are organic preparations for action, and pain is the most powerful known stimulus to supreme exertion. The organism which with the aid of increased adrenal secretion can best muster its energies, can best call forth sugar to supply the laboring muscles, can best lessen fatigue, and can best send blood to the parts essential in the run or the fight for life, is most likely to survive." 24 But fear and rage are, one hardly need be reminded, in part psychic phenomena, and hence inseparably connected with the higher centers of the cerebrospinal nervous system. Though in the main reflex and automatic, they are neverthe- less to some extent subject in man to intelligent control. Thus the way is open for a measure of rational understand- ing of the structural-functional means by which human be- ings "tap," as William James would say, and bring under direction those remarkable "reservoirs" of ordinarily unused energy about which everybody knowrs something from his Cliemico-Functional Integration 133 own experience, and upon which nobody has written more intelligently than James. An excellent beginning has been made, then, in the ex- perimental demonstration of the integration . of the endo- crinal and common glandular systems, the blood circulatory system, the autonomic and cerebrospinal nervous systems, and the emotional-psychic life of animals. Clinical Evidence of Adrenal-nervous Connection But important knowledge and general views in this field are also coming from clinical medicine, and pharmacology. A general presentation of the results reached down to 1913 is contained in Innere Secretion und Nervensystem, by H. Eppinger and others. A particularly significant body of evidence coming from this source concerns the relation between the sympathetic or middle autonomic nervous ap- paratus and the two end autonomic systems, the cranial and sacral. These two groups act, it will be recalled, antagon- istically to each other. Eppinger and others have shown that the thoracico-lumbar, or sympathetic, and cranial, or vagal systems differ in susceptibility to stimuli in different individuals, and perhaps in the same individual at different times, thus making the two groups what is called sympar tlieticotonic and vagotonic with reference to each other, de- pending on whether the sympathetic or the vagal is the more susceptible to stimuli. This difference can be demonstrated by the administration of various drugs, as adrenin and pilo- carpin. But it is known, according to Eppinger, that the thyroid toxin stimulates both the sympathetic and the vagal. From this it results that over-stimulus of either may occur through this source, and go to the extent of producing the characteristic symptoms of Basedow's or Graves's disease (rapid heart beat, exophthalmia, diarrhea, etc.). These symptoms may occur in varying degree, depending on 134 The Unity of the Organism whether the patient is sympathetico- or vagotonic, the sym- patheticotonic type of the disease being characterized by marked protrusion of the eyeballs, especially rapid heart beat, absence of sweats, diarrhea, and disturbance of the respiration; while the vagotonic type is characterized by slight protrusion of the eyes and increase of heart action, by outbreaks of sweat, diarrhea, and by faultiness in the respiratory rhythm. While some observers, like Falta, do not believe the facts now known can be definitely classed in this manner, the ef- fort, justified by some positive knowledge, has at least the merit of specifying to some extent the intricate reciprocal action between the thyroid apparatus and the nervous sys- tem, and also between the different portions of the auto- nomic system; and to this extent all students of the subject bear witness. Thus Falta : "In my opinion everything speaks for the fact that in Basedow's disease the entire nerr>ons system is in a condition of over-excitement and that the pictures presented by the vegetative nervous system are as uncommonly manifold and always changing." The indication of prime importance in this is that in these antagonistic divisions of the autonomic nervous and endo- crinal glandular systems, operating together with the other portions of the organism, there is a balancing-off or equil- ibrating apparatus through which the whole complex of vege- tative functions is carried on, all of which in turn are con- nected with the psychic functions. Probably no better il- lustration can be found of the conception of the organism as fundamentally dynamic. According to this conception nor- mality, both in function and in structure, consists not in rigid, invariable activities and organs, but in a ceaseless play of constitutively antagonistic forces and structures. By this conception the wrhole life of the organism, physical and psy- chical, may be crudely likened to the performance of the tight-rope walker, which depends on numberless balancing Chemico-Functional Integration 135 activities. Let the performer be really motionless in every part for one instant, and he falls. The treatment of tetany and its relation to internal se- cretions, especially to that of the thyroid, by Eduard Phleps in the work now under consideration, is another excellent il- lustration of how interpretation may run in accordance with this conception of the animal organism. The essence of the section, as touching this question, is contained in the fol- lowing : "On the ground of clinical symptoms authoritative clin- icians like Eulenburg, Kahler and Nothnagel explained tet- •anus as a disease of the entire nervous system. Later it was proved that this disease was not due to primary organic changes of the nervous system, but to secondary functional disorders. . . . The view of those authors, who refer the disease to the simple effect of a substance of the epithelial granules acting normally and continuously on the whole nervous system, finds here a further development of that old theory because for them the clinical picture of a regular grouping of nervous stimulus- and response-phenomena arises from an impairment of the close functional relation between the nervous system and the epithelial granules (Mac- Callum, Chvostek jun., Biedl, Eppinger, Fait a, Rudinger, Jonas, et al.). In agreement with these authors we con- ceive the action of the epithelio-secretive substance as that of a hormone in the sense of Starling and Bayliss, which must have its essential point of attack on certain reflex stations of the central nervous system." Taking cognizance, now, of the fact that most if not all the cells known to produce internal secretions arise embry- onically from epithelium, as does also almost all nervous tissue, we have the suggestion of a deep-seated combination scheme, chemical-and-nervous, for integrating the organism. The best investigated example of what is here referred to is the suprarenal bodies. It is now fully established that the 136 The Unity of the Organism inner or medullary portion of the organ, the part which pro- duces the adrenin, is developed from the same neuroblastic mass out of which the sympathetic autonomic ganglia arise. Furthermore, it seems beyond question that the so-called chromophil, or sometimes the adrenin granules in the chief cells of the functioning gland play a fundamental role. Com- bining these facts with the equally well ascertained facts that the cortex of the gland is derived from the same em- bryonic mesoblastic mass which gives rise to the genital glands ; and that in adults cortical changes in the supra- renals are intimately correlated with reproductive changes, and a general view of the factual basis on which the sugges- tion rests is before us. We may, I think, regard the sugges- tion not only as justified but as revolutionary in comparison with any theory that was scientifically justifiable until re- cently. The following further quotation from Phleps brings the idea into still clearer view : "The unqualified dependence of the nervous system on the epithelial bodies (this last used in the sense of general physi- ological considerations, and only by way of illustration), and the absolutely vital significance of this enables us to see many things in a new light. We learn that many motor, sensory and vasomotor-trophic functions of the central nerv- ous system even up to the highest reflex stations having the most complicated cortical functions, are in constant func- tional cooperation with organs which heretofore have not re- ceived sufficient consideration from this standpoint. The results compel a change of our views concerning the con- stantly dominating position of the nervous system. We may see in many of its activities only the most manifold inter- mediary roles between glandular functions which are in the closest relation to metabolism, and the sum total of all re- actions which follow external stimuli." 27 Chemico-Functional Integration 137 Summary of Present State of Knowledge In This Field Speaking generally, we may say that the trend of all re- sults, experimental and clinical, is unquestionably toward a demonstration of the closest interaction between the entire internal secretory system and both the autonomic and cere- brospinal nervous systems, this interaction affecting the whole of both the growth and the functioning of the animal organism. But we must remind ourselves again how fragmentary knowledge is in this great realm. Unanswered questions meet one on the very threshold of any portion he enters. By way of illustration, take the phenomenon of abnormal growth known as acromegaly. This malady is characterized, as the name indicates, by a "peculiar non-congenital hypertrophy of the upper and lower extremities and of the head." 2S Such, according to Schafer, is the definition given by Pierre Marie, who first fully described the disease. The main visible symp- toms consist in the enlargement of the bones of the head, hands, feet, chest, etc., especially in their terminal portions. Through such growth the nose and lower jaw, especially the chin, become protrudent. But the whole skeleton is more or less affected, and there is a corresponding over-development of the muscles, the affected person becoming abnormally strong. That acromegaly is constantly associated with an abnormal condition of the hypophysis is recognized by ap- parently all authorities. Whether the abnormality of the */ +] gland is a cause or only an accompaniment of the disease is an open question in the minds of some. However, the view of a large majority is that such a causal relation does exist. "That the acromegalic skeletal growth," says Schafer, "is produced by hypertrophy and oversecretion (or perverted secretion) of the anterior lobe is highly probable, both as the result of partial extirpation in animals and from the effect of operative removal of the pituitary tumours in man." 29 The 138 The Unity of the Organism particular issue here, it will be noticed, is the vitally im- portant one of what might be called the functional as distinguished from the hereditary cause or at least incitement of growth. In illustration of the importance of understanding the unification among these complex systems, the manifestation of which is in turn dependent upon the organism as a whole, the following from the address by L. F. Barker already re- ferred to, is impressive. "In how far these sudden and violent excitations of the autonomic nervous system which accompany strong emo- tions are due to the intervention of the glands of internal secretion, and in how far they depend upon direct neural conduction from the brain, we are as yet but ill-informed. I need only remind you of the vasodilation of the face in the blush of shame, of the palpitation of the heart in joy, of the stimulation of the sudoriparous glands which precedes the sweat of anxiety, of the stimulation of the vasoconstrictors, the pupil dilators and the pilomotors in the pallor, mydriasis and goose-skin of fright, to illustrate some of these violent autonomic excitations." 30 The references here, it will be noted, are primarily mani- festations pertaining to the surface, the integumentary parts of the body, and their scope is what especially inter- ests us. Very nearly the whole list of these parts is in- volved, and probably a complete inventory would be still more inclusive. Now notice the range of manifestations at a deeper level that are involved. "The balance maintained normally be- tween the two antagonistic systems the vagal and sympa- thetic autonomic is one of the most interesting of physio- logical phenomena. Think, for example, of the rate of the heart-beat — how constantly it is maintained at a given level in each individual when the body is at rest ; the impulses ar- riving through the vagal system just balance those arriving Chemico-Functional Integration 139 through the sympathetic system, so as to maintain a rate of approximately seventy-two beats per minute. And a similar balance is maintained in other autonomic domains (e.g., the pupils, bronchial musculature, gastric glands, gastro-intes- tinal muscle, sweat glands, bladder muscles, etc.)."30 And Barker then calls attention to the extent to which the normal processes of the body depend upon temporary upsets of these equilibria, examples of which are watering of the mouth at the smell or sight of food which appeals to the appetite through these senses, the flow of gastric and pan- creatic juices at the proper time, through indirect stimula- tion ; the sudden relaxation of the sphincter and contraction of the detrusor of the bladder in micturition ; the violent contractions of all the muscles concerned in parturition in the female, and so on. We may summarize the results of this chapter thus : (1) The researches of recent years on the internal secre- tory system and its connection with the great subdivisions of the nervous system, and with the blood, muscular, and reproductive systems, have laid a solid foundation for an un- derstanding of the chemico-ftmctional basis of the animal organism's unity. (2) The emotional phase of the psychic life of the ani- mal is proved to be in direct organic connection with this basis. From these results there naturally springs the important question : What relation has human consciousness to this same basis? An attempt to answer this question will be an unavoidable part of our treatment later of the psychic in- tegration of the organism. REFERENCE INDEX 1. Luciani II, 13 5. Bayliss 707 2. Carlson and Woelfel 49 6. Bayliss and Starling .... 325 3. Schafer (1914) 18 7. Bayliss 706 4. Hertoghe 194 8. Schafer 28 140 The Unity of the Organism 9. Luciani II, 22 10. Luciani II, 35 11. Schafer 9 12. Schafer 11 13. Aldrich 457 14. Bayliss 721 15. Waller 277 16. Waller 280 17. Waller 281 18. Langley 240 19. Bayliss 484 20. Cannon, W. B.('16) 22 21. Garrison 144 22. Cannon, W. B. ('16) ... 34 23. Garrison ; 146 24. Cannon, W. B. ('13) ... 372 25. Falta 59 26. Eppinger, et al 214 27. Eppinger, et al 217 28. Schafer 106 29. Schafer 69 30. Garrison 146 Chapter XIX THE ORGANISMAL SIGNIFICANCE OF THE INTERNAL SECRETORY SYSTEM T remains now to consider the real purpose for which the presentation of facts and views on internal secre- tions has been made, namely that of showing critically the significance of this secretory system for the organismal conception. General Inability of Elementalism to Interpret the Phenomena There is perhaps no better way of approaching this part of our task than by noticing the inability of elementalistic biology to deal in a really intelligent and consistent manner with the phenomena in this field. The breakdown of bio-ele- mentalism when confronted with the phenomena of "chemical messengers" nowhere finds more cogent illustration than in the effort to identify internal secretions with the organ- forming substances hypothesized by Sachs and others. Although in what follows the exposure of inconsistenc}T and fallacy will have to be drastic and may seem personal, the truth is it is wholly impersonal in spirit and is directed at a system of bad reasoning born of what might be called a juvenile metaphysics of the living world. The objective achievements of Jacques Loeb and others of the school he represents, in experimental biology, merit the admiration of all lovers of observational truth. One may be, too, more tolerant of their faults as reasoners 141 The Unity of the Organism than he could be but for his recognition of their high service against all the traditional forms of supernaturalism. The real case against the school is, as I see it, two-fold. First, in their zeal to substitute naturalism for supernaturalism they fail to notice that supernaturalism is in its very essence finalistic, and they are led to imagine they have attained, or can attain, natural explanations that fully supplant the old supernatural explanations. This results in the con- version of their supposed naturalism into something which is essentially another kind of supernaturalism. The second part of the case against the school is its abuse of the most common principles of the knowledge-getting processes in ob- jective biology. For the general good of the biological sciences the urgent need of reformation touching both as- pects of the case has led me to examine the particular in- stance of Loeb's treatment of internal secretions at greater length than would otherwise be justifiable. • Critique of the View That Internal Secretions are "Formative Stuffs'9 Although Loeb is the only author, so far as I know, who has expressly contended for the identity of internal secre- tions with Sachs' organ-forming substances, the assumption is so accordant with the spirit of elementalism, and Loeb is so typical and eminent a protagonist of this philosophy, that his proposal will probably find many adherents. It is consequently desirable to see what there is in the effort to bring hormones into such a historical setting. The statement of Loeb's views is contained in "The Or- ganism as a Whole from a Physico-Chemical Viewpoint," 1916. Referring to his espousal twenty-five years ago of Sachs' hypothesis to explain heteromorphosis, he writes : "At that time the idea of the existence of such organ-forming substances was received with some scepticism, but since then Significance of the Internal Secretory System 143 so many proofs for their existence have been obtained that the idea is no longer questioned. Such substances are known now under the name of 'internal secretions' or 'hormones'; their connection with the theory of Sachs was forgotten with the introduction of the new nomenclature." A case to which Loeb makes special reference as proof that internal secretions are the same as Sachs' organ-form- ing substances is that of the effect of thyroid on the meta- morphosis of the tadpoles of frogs and toads, demonstrated by Gudernatsch. The author's mode of using this case in illustration of his contention is highly instructive. He re- fers to the legless condition of the tadpoles and calls atten- tion to so much of Gudernatsch's results as pertain to these members. Gudernatsch found, Loeb points out, that where- as in the usual course of things the tadpoles live from four months to a year before the legs grow out, by feeding them on thyroid gland these members can be induced to appear at any time. "We must, therefore, draw the conclusion," Loeb says, "that the normal outgrowth of legs in a tadpole is due to the presence in the body of substances similar to the thyroid in their action (it may possibly be thyroid sub- stance) which are either formed in the body or taken up in the food." 2 When the case is presented in this way and nothing more said about it, it certainly looks considerably as if the thyroid substance or something like it is leg-form- ing substance; and such an interpretation would be enticing were it really true, as Loeb says, that no other substance seems to have such an effect. When, however, one consults the account given by Guder- natsch himself as to what his experiments were and what they established, the whole matter stands in a quite different light. First of all, the fact that in these experiments mam- malian thyroid was largely used as food for the tadpoles, thus bringing it to pass that if thyroid substance was specific organ-forming substance, then frogs' legs were produced by 144 The Unity of the Organism mammalian substance, shows at once that there is something badly askew in the theory. So we are incited to examine the facts, and particularly the reasonings, carefully. The following is taken from one of Gudernatsch's papers : 'The most striking and at the same time unquestionable re- sults were attained by thyroid feeding. . . . The influence of the thyroid food was such that it stopped any further growth but on the contrary led to an abnormal diminution of the size in the animals treated, while simultaneously it ac- celerated the differentiation of the body immensely and brought it to a premature end." 3 In other words, the effect of thyroid food was to stop the increase in size of the frog's larva and start, almost at once, its transformation into the adult. Now this transformation does not consist merely in the production of legs, but in a whole series of changes, some of which, like leg transformation, are progressive, while others are regressive. For example, one of the re- gressive changes to which Gudernatsch gives particular attention is the resorption of the tail. "Reduction of the body mass (resorption of the tail, loss of water, therefore an increasing compactness of the body, etc.)"4 more than in normal development, the author says, goes hand in hand with the progressive changes. That is, when the entire series of results of thyroid feeding are considered, and not merely one result picked out arbitrarily, then in case we choose to say the thyroid substance is organ-forming as regards legs, we should have to say it is organ-destroying as regards tail. Furthermore, if we call the thyroid substance organ- forming, consistency would compel us to recognize that one and the same substance is not only formative of legs but of numerous other organs and parts, as of the skin, mouth, respiratory and blood systems, all of which undergo, as is well known, progressive changes during metamorphosis. Nor is this complex series of morphological changes the while story. Striking and characteristic changes in the habits Significance of the Internal Secretory System 145 of the tadpoles resulted. "Towards the end of metamor- phosis the animals hardly moved about in the water. They were always lying quietly, generally on their backs. When disturbed they would move for a few seconds in a somewhat convulsive manner and then drop again to the bottom of the dish, while tadpoles fed on other material would swim about for a long time." 5 So mammalian thyroid substance is not only organ-forming for a whole series of frog organs but it is habit-forming for a variety of frog habits ! But we must not let the ludicrousness of this veer us away from the reasoning in the case. Taking the facts actually brought out by Gudernatsch, what becomes of the specificity of the substance, which according to Loeb's state- ments wras what Sachs hypothesized? "Sachs suggested that there must be in eacli organism as many specific organ-form- ing substances as there are organs in the body." The truth appears to be that thyroid substance in this case is organ- forming in much the same sense that water is organ-forming for the leaves, flowers, and fruit in a squash vine, which could not develop without water. Indeed the analogy suggested goes further than appears at first sight. As everybody knows, the effect on young plants of a scant water supply is to stunt the plant as to size and to hasten its blossoming and fruiting. That is, an under-supply of wrater has an effect on immature plants similar to that of an over-supply of thyroid substance on immature frogs, namely that of re- tarding growth and hastening metamorphosis. The total effect in each case is systemic. In other words, the real significance of the instance used by Loeb is just the opposite of his interpretation of it. Thyroid substance is organ- forming only through being organism- trans forming. Full justification of this way of interpreting the part in development played by thyroid substance is furnished by the recent studies of B. M. Allen. This investigator lias, like Gudernatsch, experimented with frog larvae. He has, how- , 146 The Unity of the Organism ever, supplemented Gudernatsch's work by depriving the larvae of thyroid altogether instead of giving them an extra allowance through feeding. Allen extirpates the entire em- brvonic thyroid from tadpoles long before any indications of metamorphosis appear. What he finds of special impor- tance for the present discussion is contained in the follow- ing : "While Gudernatsch showed that thyroid feeding acceler- ates development, this work shows that the total absence of the thyroid gland produces complete cessation of somatic differentiation at a certain stage but does not hinder con- tinued growth in size." 7 o The first part of this statement taken alone might be looked upon as confirmatory of the "formative stuff" theory of thyroid substance. But the phrase "at a certain stage" implies, as Allen's paper as a whole conclusively shows, that the exact opposite of such a conception is alone tenable. What actually happens, Allen brings to light, is that in spite of the complete absence of thyroid substance trans- formation of the larva is begun but is not carried through. That is, the organs and parts of the adult frog are laid down but (with the exception of the reproductive glands) are not completed. "It is evident," Allen says, "that the thyroid gland is in no wise essential to the earlier phases of development, but that at a certain definite stage, further development of the soma is dependent upon it." 7 It should be mentioned that Allen makes a rather special point of the accordance of his results with those of Gudernatsch. If the greatly hastened and modified metamorphosis of the frog tadpole observed by Gudernatsch is inducible by no other means than by thyroid substance (which while pos- sible is not at all certain), then is the substance causal in the important sense of being not only competent but in- dispensable. But even so it falls far short of being a com- plete causal explanation of the phenomena under contempla- Significance of the Internal Secretory System 147 tion, as Allen's results directly prove. A defect in Loeb's reasoning is his ignoring the truth that thyroid substance lacks in the case cited the prime attribute of a sufficient cause, namely full competency. The actual substance which enters into the new legs, and as far as that goes, into the other new parts, is probably provided very little, if at all, by the specific substance or hormone of the thyroid. The causal role played is the relatively humble one of excitor or stimulator to an activity not essentially new but only exceptional as to time. Of course Loeb does not need to be told that hormones incite growth rather than provide the substance itself out of which the organs and parts are built. Indeed portions of his account of this very case show positively that he is aware of this. We read: "Thus we see that the mesenchyme cells giving rise to legs may lie dormant for months or a year but will grow out when a certain type of substances, e.g., thyroid, circulates in the blood. There may exist an analogy between the activ- ating effect of the thyroid substance and the activating effect of the spermatozoon or butyric acid (or other par- thenogenetic agencies) upon the egg." This suggestion of analogy between the action of thyroid secretion and "butyric acid (or other parthenogenetic agen- cies)" is well taken. The resemblance between the two agencies, as judged by their effects on development, is cer- tainly rather close. Very well; would Loeb, then, call bu- tyric acid organ-forming substance, and identify it with the "formative stuff" of Sachs ? Certainly any substance which will rouse the latent developmental capacities of an egg into activity is in a minor sense formative, especially if these capacities are wholly unable to start without some such agency. But since butyric acid, or some one of the other dozens or scores of parthenogenetic agencies, may activate the eggs of many, many species of animals ; and since the eggs of many, many species may be activated by any one of 148 The Unity of the Organism scores of such agencies, what about the specificity of the formative substances which Loeb himself expressly says was part of Sachs' conceptions? Again, how reconcile the contention that thyroid sub- stance or something like it is organ-forming for the legs of a tadpole with the statement quoted a few paragraphs back about mesenchyme cells which give rise to legs? The Metaphysical and Logical Weakness of the View Obviously Loeb's treatment of this subject contains irre- conciliable contradictions. Is it then worthless? My answer is, no, not by any means. But how comes it that a scien- tist of his great experience and merited distinction can run into such self-destroying speculations and statements, seem- ingly without rational discomfort to either himself or others of the school which he represents? The answer takes us back to some of the most funda- mental issues between the elementahst and organismal stand- points, and though not requiring us to palliate in any degree such offenses 'against scientific reasoning, it partly explains how tolerance for such offenses is begotten, and discovers a nucleus of genuine merit in Loeb's position. Bringing the matter to as basal a statement as possible, what we find is that this whole book on the Organism as a Whole is written on' the theory that the only alternative to the assumption of supernaturalism is materialism. Instead of supernatural forces of some sort (Platonic Ideas, entelechies, psychoids, "supergenes") for explaining the organism when regarded as alive and whole, his assumption is that material elements as known to us in inorganic nature are the sufficient causal explanation of organic phenomena. Were this theory correct- -were it true that the "vital principle" must either be conceived as supernatural or that the inorganic elements taken by themselves are competent Significance of the Internal Secretory System 149 to produce organisms, then it would be impossible for biol- ogy to do much better in its reasoning and general attitude than Loeb and other elementalists do when they undertake to construct a philosophy of organisms. I agree whole- heartedly that all supernaturalism, no matter what nomen- clatorial garb it takes on, must be repudiated by the sciences of organic beings. Ideas, or psychoids, or entelechies, or "principles" of an}7 kind conceived as independent of, or even separable from, sensible objects are quite as repugnant to me, an organismalist, as they are to any element alist. The essence of my contention is that the natural substitute for +/ these imponderable things are the living, individual organ- isms themselves, and not the particles of which they are com- posed. Each and every individual organism is a natural reality by exactly the same criteria that the atoms, mole- cules, cells and tissues of which it is composed are natural realities. And since each individual is to some extent differ- ent from every other, and maintains its individuality in full possession of these differences, by its power of transforming foreign substance into its own substance, it is ultimate both as to structure and as to causal power in as deep and literal a sense as the material particles of which it is composed are ultimate. Loeb's considerable attention to the views of Claude Ber- nard is fortunate for us, since it affords a chance to show from still another angle the inevitable breakdown of ele- mentalist reasoning when it is brought face to face with or- ganic phenomena as actual nature presents them to the modern student. Loeb calls attention, properly, to the fact that one of the things on which Bernard placed special em- phasis, as Bichat before him had done, is the organizing syn- theses which go on in the living being. The real advance, it seems to me, which Bernard made over any of his predeces- sors, was the positiveness of his rejection of a vital force as something supernatural — as something, using his own 150 The Unity of the Organism words, "under the government of a special principle, a pecu- liar power what name soever be given it, whether soul, or archeon, or psyche, or plastic intermediary, or guiding spirit, or vital force, or vital properties" ; £ and his rejec- tion of these conceptions because of his recognizing that the unitariness of the organism removes the necessity for as- suming any such extraneous principle. "When we say," Bernard writes, "that life is a guiding idea, or the evolu- tive force of the being, we merely express the thought of a unity in the succession of all the morphological and chemical changes effected by the germ, from the beginning to the end of life. Our mind grasps that unity as a conception it cannot escape. . . ." 10 Up to this point the position held by Bernard is entirely satisfactory for the organismal conception as I am trying to develop it, and is, according to my view, unassailable. But the unquoted part of the last sentence contains a state- ment which reveals Bernard on a by-road leading away from the promised land toward which he was headed as long as he was speaking in terms of biology proper. The rest of the sentence follows : "and explains it as 'a force' ; but the mis- take is in supposing that this metaphysical force acts after the manner of a physiological force." Stated in a nut- shell, the by-road which Bernard is entering here is that of a kind of separatedness, but inevitable concomitance, or paral- lelism between the phenomenal and neumonal worlds which, according to the views upheld in this volume, does not exist. "We need here," Bernard says, "to draw a distinction be- tween the metaphysical world and the phenomenal physical world, which serves as its basis, but which can borrow noth- ing from it." This Leibnitzian theory, according to which "everything takes place in the soul as though there were no body, and in the body everything takes place as though there were no soul," Bernard says science "recognizes and adopts in our day." But in our day, this year nineteen Significance of the Internal Secretory System 151 hundred and eighteen, science, at least so much of it as speaks through this volume, though understanding fully what this dualist theory is, rejects it. It denies that things take place in the soul as though there were no body ; and that things take place in the body as though there were no soul. On the contrary it affirms that what in rather un- critical language we call "the body" and "the soul" are in the most intimate and indissoluble connection with and de- pendence upon each other, and together constitute "the Organism." The Form of Metaphysical Absolutism Involved A full, systematic justification of this position is beyond the province of this volume ; and in this chapter we are con- cerned solely with the "body," the strictly morphological and physiological aspect of the subject. Nevertheless, this much of contact with the "soul" aspect was unavoidable for the reason that Bernard and also Loeb have run into it in such fashion as to color deeply their discussions and out- look. This coloring is the more unfortunate and the more insistent in requiring attention from the fact that the au- thors, especially Loeb, are apparently unaware of such coloring. For example, Loeb writes on the first page of his book, after saying that the atomistic theory of matter and electricity are now in all probability on a "permanent basis" : "This permits us to state as an ultimate aim of the physical sciences the visualization of all phenomena in terms of groupings and displacements of ultimate particles, and since there is no discontinuity between the matter consti- tuting the living and non-living world the goal of biology can be expressed in the same way." Statements like this, many of w^hich can easily be quoted from Loeb's writings, leave no question about his meta- physical affinities. The conception of "ultimate particles" he Unity of the Organism as explanation of all phenomena, is exactly what I mean by elementalist absolutism. Confusion of Theory of Organisms and Theory of the Knowledge of Organisms Although the thoroughgoing metaphysical character of these statements is evidenced by the finalism which crops out at several points, this is not the aspect of the matter which chiefly interests us here. Rather what we are con- cerned with is the fact that affirmations about the "aim of the physical sciences" and the "goal of biology" do not belong, properly speaking, to the provinces of physical science and biology at all, but to quite a different science, namely that which deals with the nature of knowledge itself. The "physical sciences" are the vast accumulation of man's positive knowledge, theories, hypotheses, and so forth, about physical nature; they certainly are not physical nature it- self. Consequently a statement of the character and aims of that knowledge is not a statement about the phenomena to which the knowledge pertains. And the same reasoning applies to the affirmation about the goal of biology. All this is only another way of saying what Loeb him- self virtually tells us, namely that his entire discussion of the organism as a whole is made from the standpoint of one particular theory of the ultimate nature of living beings, that theory being the mechanistic. Recall the complete title of the book The Organism as a Whole From the Physico- Chemical Viewpoint. To treat the subject from this view- point is of course perfectly legitimate. When, however, the assumption is made that such a treatment is the only really legitimate one because it rests on ultimate truth, then sound science is bound to protest, chiefly because of the obvious biological inadequacy, and at some points, perversion and contradiction displayed in the treatment. Significance of the Internal Secretory System 153 This brings us back to the way internal secretions are dealt with by Loeb. His failure to distinguish between the two very distinct fields of theory above indicated, namely theories about the phenomena of living beings, and theories about knowledge of these phenomena, largely explains the defects of the theoretical parts of his work. And we are now in position to give our criticism greater explicitness. Consider for example in the light of what has just been said about confusion relative to kinds of theory, the irreconcil- able statements, cited on an earlier page, that the mesen- chyme cells give rise to the legs of the tadpole, and that thyroid substance is organ-forming substance for the legs. Stated briefly the case seems to be thus : Loeb recognizes, as every one must, that internal secretions constitute a physico- chemical agency for bringing about that harmonious de- velopment and functioning so characteristic of the organ- ism. But this harmony is one of the very things which has seemed to some biologists inexplicable without the assump- tion of supernatural influences of some sort ; hence Driesch's attempt to modernize the ancient entelechy. But since in- ternal secretions play the role that entelechies are supposed to play, namely that of establishing and maintaining the unity and equilibrium of the organism, the need for ente- lechies no longer exists ; at least, this would be so for all persons who do not contend that "ultimate explanation" is the "goal of science." To those who hold these absolutist beliefs as to the power and aims of science three favorite courses are open and are followed by different representatives of the school, depend- ing on the taste, training and outlook of the person. One course consists in pointing out, taking an illustrative case, that internal secretions, being only contributing causes, do not constitute an ultimate explanation, so that entelechies or something similar are as necessary as before. This would be the course followed by the vitalistic wing of the absolu- 154 The Unity of the Organism tist school. For them internal secretions would be, in so far as they contribute to the harmony of the organism, merely agencies produced and used by supernatural causes. Another course, and perhaps the one most frequented by elementalists, would be to contend that internal secretions are sufficient as a causal explanation of organic unity to make the entelechy or any similar notion quite superfluous, even though these substances are far from a complete ex- planation. The reasoning of this group of elementalists as to this situation is substantially as follows : although in- ternal secretions fall far short of fully explaining organic unity and harmony, the action of these being merely that of incitors and inhibitors, they are yet genuinely causal, genuinely physico-chemical and so are on the road toward complete explanation of the phenomena. All that is nec- essary consequently, is to believe that still further advance in the same direction will reach finallv a full element alis tic •/ explanation ; that is, an explanation which will have no need of either supernatural elements or the organism as a whole. The attitude of this large class is one primarily of faith rather than of reliance on positive knowledge ; they are inspired more by what they believe they will do in the future than by what they actually have done. They are preemi- nently men of promises. Although their achievements in experimental science are indeed large, the results reached by them are prized more on account of what they are believed to augur for the future than for their present meaning and worth. Then, finally, there is the group of elementalistic absolu- tists, of whom the author of Tlie Organism as a Whole from the Physico-Chemical Viewpoint is one of the most eminent in our day, who, as we have pointed out, by confusing theo- ries about objective phenomena with theories about the knowledge of such phenomena, are led to affirm that such phenomena as the unity of the organism are fully explained Significance of the Internal Secretory System 155 by internal secretions, when as a matter of fact they are only partly explained thus. The surprising thing about the confusion of this group is that wholly irreconcilable positions are held with impun- ity, such for instance as those according to which thyroid substance is held to be the organ-forming substance of frogs' legs in one part of a discussion, and mesenchyme cells are acknowledged to be of this nature in another part. The contradiction is, to be sure, often of such character as easily to escape the uncritical reader; but as to the au- thors of such contradictions no other explanation seems possible than that of wrong habits of scientific thought be- gotten of untenable a priori conceptions. For example, a hasty reading of the discussion under review might lead one to suppose that thyroid substance is not, after all, regarded by Loeb as anything more than one contributing cause of frogs' legs, mesenchyme cells being recognized as another cause. Close attention to the text does not, however, war- rant this generous interpretation of the author's position. Going back to his espousal of the theory of Sachs and other botanists as to organ- forming substances, we read : "Specific shoot-producing substances are carried to the apex, while specific root-producing substances are carried to the base of a plant. When a piece is cut from a branch of willow the root-forming substances must continue to flow to the basal end of the piece, and since their further progress is blocked there they induce the formation of roots at the basal end." n If this means anything it means that the shoots and roots are actually built up by material carried about in the wil- low branch. There is nothing in the language that can be interpreted as meaning that shoot-and-root-forming sub- stances are mere stimulators of some other substances which become the actual shoots and roots. Yet it is with forma- tive substances of this sort that Loeb in some parts of 156 The Unity of the Organism his discussion explicitly identifies internal secretions. "At that time the idea of the existence of such specific organ- forming substances was received with some skepticism. . . . Such substances are known now under the name 'internal secretions' or 'hormones' ; their connection with the theory of Sachs was forgotten with new nomenclature." Then follows the reference to the tadpole legs ; so that were consis- tency really a jewel to the author, he could not escape mean- ing that the substance of the legs was actually derived di- rectly from the particular internal secretion in question, in this case thyroid substance ; and the later statement about the formation of legs from dormant mesenchyme cells through the mere activating effect of thyroid substance is by implication contradicted. This brings up again a matter about the interpretation of development which we have dwelt upon in several other connections, that of protest against rejecting the indubi- table evidence of the senses in favor of a priori conceptions. The crucial question in the present case is this : which is the more fundamentally organ-forming substance for frogs' legs, the mesenchyme cells which "though giving rise to legs may lie dormant for months," or the thyroid substance which may stimulate these cells into premature activity? While Loeb's discussion does not raise this question definitely, the implication is unescapable that thyroid substance is for him the more fundamental. What else is the meaning of the contention that this substance is organ-forming while no- where do we find the mesenchyme cells so designated? Yet the observational evidence is that the production of legs is accomplished through the transformation of mesenchyme and other cells which in the larva are not leg-substance, but in the adult are leg-substance. Hence it follows that so far as actual observation is concerned the mesenchymatous and other larval substances are more entitled to be called organ- forming than is the thyroid substance. Significance of the Internal Secretory System 157 An Illustration of Neglect of Fact By Elementalist Theory These reflections lead to a still deeper level of the inherent faultiness of elementalistic absolutism in biology, the toler- ance which it engenders for ignoring relevant facts ; or stated otherwise, of arbitrarily selecting from a great com- plex of facts just those which suit the argument, and dis- regarding all the others. For example, recall Loeb's ref- erence to precocious leg-production in frog tadpoles as though the effect of thyroid feeding stood alone rather than as one among a great concatenation of effects, some con- structive and some destructive, this complex of phenomena constituting the metamorphosis of the young into the adult. Loeb's use of Gudernatsch's results amounts to a positive obscuration for the reader of what these important experi- ments really teach. Only by the culling of facts to suit the argument and the use of certain words and phrases, as "influence," "responsible for," and so on, with equivocal meanings, can these results be made to support the conten- tion that thyroid substance is specific organ-forming sub- stance for frogs' legs. The patent fact is that certain mesenchyme and other cells of the larva are organ-forming for legs, and there is no straightforward way of talking about the causes of the transformation of a given group of more or less undifferentiated tadpole cells into the much enlarged and highly differentiated group called a leg, with- out recognizing the whole organism as causal of the par- ticular transformation. Probably no set of discoveries con- cerning the development of the individual has ever been made which so objectifies the means employed by the whole in producing and correlating its constituent parts as those on internal secretions ; and not the least significant fact is that these substances are themselves produced by the or- ganism. Even were Loeb's contention valid that thyroid substance 158 The Unity of the Organism is specific organ-forming substance, the indubitable fact that in normal development this substance is itself a product of the organism's activities, throws it into a very subordinate place as a cause of development. The truth is, the main upshot of the effort to explain ontogeny on elementalistic principles amounts to an effort to avoid recognizing the most positive and definite entity in the whole situation, namely the organism taken alive, normal and untampered with. A Peculiar Element alls t Objection to the Organic Whole 'We now come to the last point to be noticed in connec- tion with the element alist attempt to deal with internal se- cretions as related to the organism as a whole. Instancing the familiar way in which a particular part of a flat-worm will give rise to a new head after being cut away from the original animal, when no head would have been formed at this place had not the animal been cut, Loeb writes : :£7'-natural, while for the Materialists the same realm is largely i?zfr«-natural. Theories of Animal Behamor in Relation to the Science of Zoology This somewhat protracted though wofully insufficient treatment of neural integration may close with a brief section on some of the still larger biological and methodo- logical implications of the conclusions reached. Special at- tention is called to the fact that the culminating part of our argument has involved data and conceptions which are as unequivocally zoological, morphological, and physiologi- cal, as any of the data and conceptions are unequivocally physical and chemical. Physical chemistry, or any other aspect of inorganic chemistry, is utterly powerless, so far as we can see, to discover such facts, as for example, that oxygen, carbon, nitrogen, etc., possess latent "doscarecious" powers. This final section is in the direction, consequently, of establishing the parity, to claim the least, of zoology? botany, morphology, and general physiology, with chemistry and physics, in the great complex group of biological science. We may first allude to a favorite mode of expression of materialistic element alls ts. Whenever fuller analysis lias proved some group of animal phenomena not hitherto con- nected directly with physico-chemical substances and forces, Implications of the Theories of Nerve Action 209 to be in reality dependent on such agencies, this school is wont to remark in substance that investigation has finally "transferred" the phenomena from the provinces of zoologv, morphology, general physiology and the other sciences of animal life, to physics and chemistry. Our argument puts beyond question the logical inadequacy of such a statement. Analysis does not by any means transfer the phenomena from zoology, etc., into physics and chemistry. Neither analysis nor any other agency can any more take the study of animal phenomena away from zoology and put it into physics and chemistry than it can take bread-making away from the baker's art and put it into physics and chemistry. The chemist may undoubtedly take to bread-making and find that his new employment has much in common with his old; but in so far as he really succeeds at the new, he is more a baker than a chemist. He has not transferred bread-making to chemistry, but if anything has done just the reverse. What analysis actually docs in these cases is to extend the bounds of physico-chemical forces and laws into zoology* morphology, etc., and to prove that if zoological, morpholog- ical and physiological undertakings are to move into ever greater fullness, aid from physics and chemistry is indis- pensable. Thus critical examination of the reasoning of elemen- talist biology reveals the logical fallacy in any sort of state- ment which involves the assumption that the older sciences of organic beings, like taxonomic botany and zoology, geo- graphical distribution, morphology, general physiology and so on, are not and never can be relegated to places of minor or secondary importance in biology. But it is the practical harmfulness of such assumptions rather than the logical fallacies underlying them which chiefly concern us in this volume, and no part of our whole subject is more vitally affected by such harmfulness than this of the behavior, even the purely tropistic behavior, of animals. The whole round 210 The Unity of the Organism of animal biology — attitude toward research problems and undertakings, valuations and interest in different fields of knowledge, educational aims and method — all are affected. In the light, for instance, of such a complex of animal behavior as that presented by the northern fur seal, its mating, breeding, migrating and other habits, the conten- tion that the myriads of complicated phenomena which go to make up animal life can be understood by converting zoology into a laboratory and experimental science, to the end of analyzing the phenomena into their "simple elemen- tary components," is so ludicrous as hardly to need argu- mentative refutation. Indeed, it seems as though persons obsessed by a theory to the extent of being impervious to the ludicrousness of the contention, are likely to be also impervious to the true reasoning involved in it. It may, I think, be assumed that so much of zoology as has formed this remarkable conception of itself will before long drop into the background by scientific gravitation despite its present great vogue. One of the leading motives, consequently, of this con- structive part of my enterprise is to establish the essen- tiality of general zoology and its time-sanctioned depart- ments on so solid a basis of philosophic reasoning that the necessary methodology of the regenerated science of the future will be clearly seen in broad outline. If the considerations inadequately presented in these last pages and in other parts of this volume once get secure lodgment in biological thought it will become manifest that the "behavior" of any animal species (as of the fur seal, to take at random any one of thousands of species that would illustrate the point quite as well) can mean nothing less to a really scientific biology than the whole series of activities of at least one individual animal from its birth to its natural death. Consequently an "understanding of the complicated phenomena" thus presented can not be secured Implications of the Theories of Nerve Action by any amount whatever of analysis, but only through an endless series of never-divorced analyses and syntheses, this series running on through years of effort by scores of investigators in the field (on the Pribilof Islands, on the Behring Sea and far down into the North Pacific Ocean) and in the laboratory, by general zoologists, mammalogists, anatomists, embryologists, physiologists, comparative psy- chologists, bio-chemists and physical chemists. How, let one ask himself, would the resolving of a fur seal's behavior into reflexes as the simple elementary com- ponents of that behavior, contribute to an understanding of the annual oceanic migration of the animal or the fighting of the males for the females, if that analysis accomplished nothing beyond proving a certain measure of identity be- tween the reflexes of a fur seal and, for instance, those of an earthworm? Or how would the understanding sought be enhanced by carrying the analysis to a still deeper level — to the physico-chemical level — and discovering just how oxygen, or some particular proteid substance, participates in the reflex? We must never lose sight of what the biolo- gist's task is as regards understanding. It is to investigate for the purpose of understanding the facts presented by living beings in nature. The behavior of the fur seal as the animal lives its normal life is what is to be studied in the case chosen, and one of the most characteristic things in this particular behavior is a yearly journey of several thou- sand miles through the Pacific Ocean. That is one of the phenomena to be studied and understood, and no amount of analysis resulting in discoveries which do not apply par- ticularly to that particular phenomenon can be admitted as an explanation of that phenomenon. As compared with any of the other natural sciences, biology is preeminently the science of individuals — or natural objects which though alike in innumerable attributes are unlike in innumerable other attributes, and in no aspect of organisms do the dif- The Unity of the Organism ferentials which make individuals, species, genera and so on come out so importantly as in behavior. The evidence being now overwhelming that all organic phenomena, including behavior, are dependent upon physico- chemical substances and forces, one of the most pressing ques- tions of procedure in biological research is that of bringing the older and, generally, less exact natural history aspects of the science into closer, more vital cooperation with its newer experimental and more quantitatively exact aspects. Specif- ically stated, work of the type long prosecuted by explor- ing expeditions, botanical and zoological gardens, museums, botanical, zoological and biological societies, and govern- ment biological surveys ; and that of laboratories in the strict modern sense, the morphological, physiological, and bio-chemical laboratories, must join hands more closely and effectively than they have heretofore to insure continued progress in the organic sciences. Several movements of the day in biology could be mentioned whose meaning, viewed from our standpoint, can hardly be mistaken. Perhaps the most conspicuous of these is that congeries of research ac- tivities known as ecology. In spite of frequent deprecia- tive comments about ecology, especially because of its in- definiteness as to both content and delimitation, it has the merit — from our standpoint the very great merit — of facing organic nature as it actually is, that is, of having for its subject matter the modes of life of organisms as nature presents them, and hence of recognizing the laboratory as an agency, but only as one among other agencies, for deal- ing with its subject. As to method, while ecology recognizes the indispensability of the laboratory and experimentation in the narrow sense, it refuses to let such experimentation usurp the whole of its interest and effort. So our study of the organism's integratedness as exem- plified by its activities, that is, by its behavior, and by the mechanism through which these activities are carried on, Implications of the Theories of Nerve Action leads to the somewhat unexpected though entirely natural result which may be summarily stated thus : To gain un- derstanding of the behavior of living beings is admitted by everybody to be the chief reason for investigating such ac- tivities. Due consideration of the nature of the activities and of the nature of understanding makes it certain that the phenomena themselves are highly integrative and integrated, or synthetic, and that understanding of them depends as much on synthetic knowledge-getting as on analytic knowl- edge-getting. Perception of this last truth necessitates, again, a sort of synthesis, or integration, of the numerous research agencies. REFERENCE INDEX 1. Loeb ('16) 285 9. Loeb ('02) 94 2. Loeb ('12) 70 10. Loeb ('02) 101 3. Loeb ('16) 284 11. Schrader 177 4. Loeb ('16) 257 12. Holmes ('06) 313 5. Loeb ('02) 7 . 13. Holmes ('06) 315 6. Friedlander 363 14. Luciani iii, 355 7. Loeb ('02) 85 15. Loeb ('02) 5 8. Loeb ('02) 91 Chapter XXII PSYCHIC INTEGRATION Preliminary Remarks (a) Absolute Discrimination Between Re-flex and Psychical Phenomena Not Necessary T will be recalled that in our discussion of neural inte- gration we limited ourselves strictly to those manifesta- tions and activities of organisms which are, so far as ob- servation can determine, strictly reflex, that is, show no evidence of intelligence and volition, or even necessarily of instinct. What we have to do next is to consider the unity, the integratedness of the animal organism as manifested in the vast array of its activities which by universal consent are designated by such terms as instinctive,, emotional, vo- litional, conscious and intelligent. Be it noted that this aim will not exact of us, any more than did the last, a sharp delimitation between reflex or purely mechanical acts and psychical or conscious acts. Just as in the former discussion we were concerned with the integrative character of those acts which are indubitably reflex, so here our object is to study the integrative or syn- thetic character of those acts which are indubitably psychi- cal. We shall now be dealing with acts which have unques- tionable psychical attributes, that is, show something of individual plasticity and something of correspondence to individual needs; which are, in other words, to some degree individually determined to meet individual requirements either of external or internal imposition and intention. 214 Psychic Integration (b) The Organism an Original Datum in All Problems of Psychic Life Another preliminary remark of high importance concerns the question of what, precisely, it is with which we have to do — of what we start from and what is ever in sight, in the discussion. Our fidelity to the organism, living in its natural setting, as the foremost objective reality in this treatise, prevents us ab initio from being satisfied with a Body, and a Mind or Soul, as these have figured from time immemorial in discourse about the higher animals, particularly about man. If in all the world there is such a thing as objective truth, what we start with and have ever to deal with in studying psychic phenomena, just as in studying all other phenomena of animals, are individual objects or bodies of very particular construction and activity. And by no pos- sibility can consistent thought and statement avoid acknowl- edging that that vast assemblage of acts and other manifes- tations which are called psychical are yet only part and parcel of the still vaster assemblage of acts and manifesta- tions presented by the very same living objects, that is, by or- ganisms. Our occupation will be basally with an object, some particular organism, having innumerable attributes, which being classified fall rather roughly into two great groups, one of which we name physical or material and the other psychical or spiritual. For short, the physical or material group is called the Body, while the psychical or spiritual group is called the Soul or Mind. Our discussion, then, will never lose sight of the fact that the acts with which we deal are acts of the organism and not of any of its parts merely, whether these be conceived as material or psychical. No matter how far particular acts may be dependent upon, and so explicable by, particular parts, this dependence can not in reality be the whole story, 216 The Unity of tire Organism for the sufficient reason that the parts are, finally, non- existent except as derivatives of and dependencies upon the organism, as our whole treatise has abundantly shown. Discussion of the Nervous System, the Brain, the Cerebral Cortex, Neurones, Reflexes, the Senses, Responses, Emo- tions, Consciousness, Will, Reason, and so on, as though any of these are now or ever have been or ever will be independent entities, or tilings to which the organism is subordinate, is from our standpoint one of the deep inadequacies and mis- fortunes of much biological and psychological thinking. To the whole attitude of the zoological naturalist, who by na- tive endowment and by training is imbued with the spirit of his motto "neglect nothing" in the study of animals, this liabit of the special sciences of animal life is intolerable. The ancient problem of the relation of "Mind" to "Body" is one of those problems which run on endlessly in discussion simply because the partisans of one theory or another never know exactly what they are discussing — never know just where they start from, in what direction they are going, or what the end would be like if they reached it. Lest this statement be taken as foreshadowing both a right statement and a "final solution" of the problem, I affirm very positively that it foreshadows nothing of the sort. All I hope to do is to add considerably to a clear statement of the problem, to add a little to our comprehension of whither we are going, and to contribute a bit to the "final solution," whatever that may mean. The real problem of psychic integration formulates itself, for us, in a two-parted way: Given any particular act or action-system* which is unquestionably psychical, (1) how many and what parts of the organism are essentially in- volved in it? and (2) does the act or action-system bear such * This phrase I borrow from Jennings (Behavior of the Lower Organ- ixms, p. 107) and mention incidentally here that we shall find it ex- tremely useful later on. Psychic Integration relation to other acts or action-systems and to material parts of the organism as to warrant the ascription to these acts of causal influence on other acts and on the material parts ? (c) Provisional Classification of Psychical Facts A third and final introductory remark touches on the question of what shall be recognized as contained in the organism's system of psychic attributes. Following our regular custom of beginning with the phenomenon under con- templation at its fullest, most indubitable expression, we shall not go far amiss if we accept the time-honored trium- virate of feeling, will, and intellect as the most obvious sub- groups of highest psychic attributes ; for only a hopelessly sophisticated philosophy and psychology can hesitate to acknowledge that every full-grown, normal, civilized human organism, at least, is at once a sort of reservoir of feeling, sentiment, and emotion ; a dynamo of resolution and exe- cution ; and a granary of intelligence and reason. ( See, for example, Tlwikvng, Feeling, Doing, by E. W. Scripture.) Perhaps the only thing that needs saying about these sub-systems of mind is that our general standpoint aligns us squarely writh the tendency in present-day psychology to accept them for what they actually are, striving to become acquainted with them and to assess their importance on this basis. To ascertain first of all the facts on the psychic side of the living animal, then next to interpret, to correlate, to explain these facts, are cardinal principles of procedure in our enterprise. For one thing, as an evolutional zoologist of many years' practice in speculating on how animal parts originated (even those of almost infinite simplicity as com- pared with the mind of man), I am too familiar with the limitations and pitfalls of the genetic method to be be- guiled into making some one theory of the origin of mind The Unity of the Organism the corner-stone of my interpretation.* Furthermore, as a naturalist faithful to the mandate "neg- lect nothing," I am in full accord with psychology's aban- donment of the earlier supposition that a leading aim of psychology must be to prove that some one psychic province is all-dominant, the others being merely secondary and trib- utary. Thus all forms of the theory that the psychic empire is at bottom Intellect, the heaven-ordained monarch of which is Unconditioned Ideation, are incompatible with our stand- point. Something of the weight and variety of authorita- tive sanction which are pitted against us here is indicated by such names as Descartes, Locke, Leibnitz, Hume, Kant, and Herbart of the proximate past, and Wundt, Royce, Howison and Bradley of the immediate past. And theories like those of Fichte, Schopenhauer, Hart- mann, Nietzsche, and divers pale, fitful present-day lights, which would accord to Will hegemony over the entire psychic realm, are still less tolerable to us. Feeling has won its rightful place in psychology so recently that there seems little danger of its pushing its claims to position and power beyond reason. Except perhaps in the form of sensationalism, or the theory that all knowledge ac- tually does originate in sensations, psychology of the west- ern world appears never to have attempted seriously the deification f of Feeling as it has of Reason and Will. When * I count it as one of the pieces of good luck in my scientific career that, through no merit of my own, a technical memoir of mine containing an elaborate theory of the origin of the vertebral column has lain in editorial keeping unpublished for a decade and a half. t It is possible, as my friend Professor G. M. Stratton suggests to me, that the German philosopher Fr. H. Jacobi, came nearer doing this than any one else. His teachings gave, however, a definite place to positive knowledge, so that, according to Hoffding, his faith and his knowledge constituted two distinct philosophies. What he wrote probably does not, consequently, contradict the statement in the text. Jacobi seems not to have exerted much influence on the main current of German philosophy and life. Psychic Integration Thomas Hobbes identified imagination with fancy, "orig- inal fancy" with sense, and "decaying sense" with memory, and held sense to be caused by "so many several motions of the matter, by which it presseth our organs diversely," and when he defended the general doctrine that "there is no conception in a man's mind which hath not at first, totally or by parts, been begotten upon the organs of sense," 1 he did indeed blaze a trail which might easily lead to an over- exaltation of the sensuous and emotional side of life. But the eminently practical character of Hobbes' undertaking being remembered (he was writing not for the love of specu- lation but to save his country from political chaos and mis- ery begotten as he believed from false theories and impossible desires and ambitions) one may expect to find in him ele- ments of steadiness and restraint which would make for safety in speculation. One such element is clearly seen in his opinion that he who is "born a man" and lives "with the use of his five senses" has all the native equipment necessary to realize the best in him both for himself and for his country.2 The necessity of being "born a man" is the point to be especially noticed. That, with all it may imply, is on a par with the necessity of using the five senses. So whatever of scientific hobby- riding under such captions as "sensationalism," "empiric- ism," "associationalism," may have followed in the wake of Hobbes' writings, Hobbes himself, I am quite sure, was at heart a genuine organismalist and is entitled to high es- teem as one of the very first moderns to speak strongly for the importance of the body generally to the psychic life of man. Listen to this : "Natural sense and imagination are not subject to ab- surdity. Nature itself cannot err ; and as men abound in copiousness of language, so they become more wise, or more mad than ordinary." "Between true science and erroneous doctrines, ignorance is in the middle." 220 The Unity of the Organism Having completed a reconnoissance of the field in which we are to work, of its expanse, its contents, and its main subdivisions, we are prepared to take up the task proper. Approaching it from our standpoint, one naturally sur- mises that between the organism's neural unity as manifested by its reflexes studied in the last chapter, and its psychical unity known to psychology and to be considered presently, a vital unity of still higher order exists. By unity I mean a unity so intimate, so reciprocating, so mutually constitutive that the term parallelism, with the meaning given it in much of recent psychology, is wofully inadequate for it. Such a unity, if it exists, must be sought by inspecting the entire gamut of psychic life, from the simplest responses to stim- uli on up through simple reflex responses, the tropisms, the primal affective and emotive responses, through the perceiv- ing, the imagining, the conceiving, the reasoning operations, to the very highest constructive human mental achievings. Likeness Between Tropistic and HigJwr Psychic Activity An important move, starting from the highest phase of rational mind, has been made toward recognizing the nature of this unity. This move is the more significant for our enterprise in that the investigator who has made it is neither an elementalist nor an organismalist, but an eminent sub- jective idealist. Josiah Royce is the student who has per- formed this service. Stated in a single sentence, the ad- vance he has made toward discovering the union consists in the recognition of certain fundamental resemblances be- tween some of the very highest operations of man's mind and the pure tropistic operations of lower animals. Royce's contribution to this subject is contained in his Outlines of Psychology, and nowhere else so far as I know. From the preface of this book I gather the following, partly by way of quotation and partly from obvious inference. Psychic Integration 'To my mind," says Royce, "an interesting side-light has been shed upon the well-known controversies between the associationists on the one hand, and the school of Wundt and the partisans of 'mental activities' generally, on the other, by the stress that Professor Loeb has recently laid upon the part that what he calls 'tropisms' play in the life of animals of all grades." 4 Then after telling in a few sentences what tropisms are, Royce continues : "Now it is especially notable that the 'tro- pisms' of Loeb are not, like the 'reflex actions' of the theories, modes of activity primarily determined by the functions of specific nerve-centres. Furthermore, they are more general and elemental in their character than are any of the acquired habits of an organism." (At this point Royce takes up, for a moment, a matter to one side of my main purpose, namely the problem of "self-activity" and "spontaneity" ; so I ven- ture to change somewhat the order and emphasis of his ar- gument.) "Now it has occurred to me to maintain, in sub- stance, that the factor in mental life which Wundt's school defines as 'Apperception' . . . may well be treated, from the purely psychological point of view, as the conscious aspect or accompaniment of a collection of tendencies of the type which Loeb has called 'tropisms.' Then we have : "Wundt has insisted that his 'Appercep- tion' is no disembodied spiritual entity. I conceive that Loeb has indicated to us, in the concept of the 'tropism,' how a power more or less directive of the course of our asso- ciations, and more general than is any of the tendencies that are due, in us, to habit, or to specific experience, can find its embodiment in the most elemental activities of our organism." What, now, is the bearing of this idea of Royce's on the main theme of this chapter, the organism's unity as mani- fested in and influenced by its psychic life? As an initial step toward answering this question, the reader is asked to 222 The Unity of the Organism recur to the chapter on tropistic activities and their an- atomical groundwork, recalling that it was the special aim of our discussion to show the inevitable organismal trend of the whole doctrine of tropisms. It should be remembered also that tropisms are, all of them, probably, beyond ques- tion adaptive in fundamental nature; i.e., they work in the interest of either the individual as a whole or of the species to which the individual belongs. The circumstance that under occasional more or less artificial conditions the ac- tivities of an animal may result in injury to it or even in its death, is not proof that on the whole those activities are not advantageous. A horse or man may make himself sick now and then by taking the wrong kind of food or too much food, but this does not prove eating to be useless on the whole, or non-adaptive. Another important thing to bear in mind about tropisms is their automaticity, or preferably their intrinsicality. They are rooted in and partake of the very essence of the or- ganism— so much so that they manifest themselves inevitably when the right external and internal conditions are present, whether the general ends which they normally serve are at- tained in the particular instance or not. The flight of the moth toward the flame, even at the sacrifice of its life some- times, is a manifestation of a tendency that works, on the whole, for the good of the animal. That the moth follows the impulse even to death merely shows how tremendously deep-seated this type of reaction is. That the activity may result in injury or death in a special case is just because the case is special, i.e., it is a departure from the regular con- ditions under which the reaction-type became incorporated in the organization of the creature. Being always poised for a particular kind of action, and having a supply of en- ergy to execute the action, are unquestionably among the most distinctive attributes of animal organisms. Such or- ganisms are distinguished from plant organisms not only Psychic Integration by the present fact of inherent activity of the animal, but by their inherent preparedness for acting to meet new and more or less unusual situations. This action and action- readiness are the real meaning of the neuro-muscular system. All biotic organization is anticipatory in various ways, but animals are almost exclusively anticipatory in action. It is just these attributes that Royce recognizes as com- mon ground between certain of the highest psychic activi- ties of man and tropistic activities. With this overplus, and in some cases useless or even injurious activity (in- stanced by the flight of the moth toward and around the flame), let us now pass to the upper end of the gamut of animal activity for illustrations. A very few must suffice. The first chosen is one of exalted creativeness in art. From the vast domain of art a more instructive illustra- tion of over-wealth of self-activity can hardly be found than is afforded by William Shakespeare. A recent investigation of his works undertaken with a view to finding what they tell about the "native endowments of the author" and prose- cuted with that love for accurate, exhaustive knowledge which is the very soul of modern science, leads to the result that of these endowments "the most outstanding perhaps is his exuberant vitality." This characteristic of the man is exhibited in the "reckless volubility of almost every char- acter, the piling up of fancy upon fancy, of jest upon jest, the long embellishment of humor and foolery and horseplay for no other reason than the delight they afford." 7 And incidentally, the strict individualism of this sort of thing is exemplified by one of these same Shakespearian characters: "Come, come," says Mercutio to Benvolio, "thou art as hot a Jack in thy mood as any in Italy. . . . Nay, an there were two such, we should have none shortly, for one would kill the other." "What has Queen Mab to do with the ac- tion of the play of Romeo and Juliet? Nothing; but Mer- cutio mentions her, and before any one can stop him he has The Unity of the Organism poured forth fifty lines of purest fantasy. . . . Whole scenes," this student declares, "exist for no other reason than that the author's brain is teeming with situations and humor and infinite jest." Now I hear in imagination expressions of astonishment, rising to protest, even to ridicule, on the part of some biol- ogists, and to horror on the part of some literateurs, at the idea of suggesting that there is anything really in common between the two groups of phenomena here placed side by side — the activities of a moth and of Shakespeare ! For the moment I do no more in reply than ask the reader to take cognizance of the fact that the whole training and occupa- tion of the naturalist consist largely in comparing all sorts of things, inorganic as well as organic, which to cursory observation seem unlike, for the purpose of finding whether closer and broader examination can not discover resem- blances and affinities which may throw light on the ever- insistent problem of origin and causal relationship. From that procedure, and that alone, initially, came the theory of organic evolution. It is the quintessence of the organic method. To him who is so instructed and disciplined that the recognition of likeness and kinship between, for example, the prothallus of the fern and the flowering plant, or between a horse's fore-foot and a man's hand, will receive no shock from the comparison. The intrinsic justification of the comparison will be deferred until we have a few other illus- trations before us. Another illustration will be taken from an author, J. J. Rousseau, whose activities stand about mid- way between art proper and science proper. "I felt," Rousseau says in his Confessions, "that writing for bread would soon have exhausted my genius, etc.," Again: "Nothing vigorous or great can come from a pen totally venal." And finally: "In a severe winter, in the month of February, and in the situation I have described, I went every day, morning, and evening, to pass a couple of Psychic Integration hours in an open alcove which was at the bottom of the garden. ... It was in this place, then, exposed to freezing cold that without being sheltered from the wind, I composed, in the space of three weeks, my letter to D'Alembert on theatres." If this sort of thing, one may note in passing, is a case of "struggle for existence," the existence struggled for is on the highest plane of psychic life and not on the plane of mere brute continuance. The only other example will be one of activity in science proper, i.e., "pure intellect" as far as there is such a thing. The case of some man devoting the best of his life to the working out of a great germal idea — an Aristotle, a Coper- nicus, a Galileo, a Kant, a Darwin will serve our purpose best. Of these we choose the case of Darwin. Consider first the youth and the young man keenly alive to the flood of sense impressions pouring in upon him from external nature, and mentally — "internally" — "restless," as Royce would say, from an undefined though strong dissatisfaction with the stereotyped school and university curricula and modes of dealing with subjects. Later comes the set of environ- mental influences (chiefly through the naturalist Henley), quite incidental to his regular, prescribed environment, to which he responds with eagerness and effectiveness — an al- most automatic choosing of fields of intellectual activity. Out of all these fragmentary and by-the-way experiences- "contents of consciousness" — there is organized a body of natural knowledge, and such definiteness and promise of ten- dency as to justify an appointment to a post of consider- able responsibility and unique opportunity, that of natural- ist to H. H. Exploring Ship Beagle. During the voyage and from the new and strange con- tacts with nature afforded by it, there arises another state of "restlessness," this time concerning the origin of organic species, the "mystery of mysteries," as Darwin himself put The Unity of tlie Organism it. A matter deserving special notice is that the truly for- ward, the creative step came after, and was conditioned upon, a period of dissatisfaction with the prevalent teaching on the subject. Then the considerable time of semi-con- structive observation and thinking and feeling under guid- ance of the general surmise that species arise naturally and not supernaturally, as all his earlier experiences — "contents of consciousness" -had taken for granted. And at last the final, for him, great conception, the hypothesis of the "strug- gle for existence" and "survival of the fittest" as a cause of the transformation of species. The suddenness and spon- taneousness with which this idea emerged into consciousness should be specially noticed. Once the merest suggestion of it hove in sight, the whole hypothesis formed itself, organ- ized itself, rapidly and completely. The sense in which the process may justly be called spon- taneous is important. Although we well know that the famous hypothesis was suggested by the reading of Malthus' work on population, we know equally well that the most es- sential features of the hypothesis were not contained in the teachings of Malthus. There was something genuinely new in the hypothesis. Out of the former total of experiences came that which did not actually exist in those experiences. Although the hypothesis was clearly a product of something which went before, it was a synthetic product in the strictest sense, in essentially the sense that a chemical compound is a synthetic product of its interacting elements, the sense that the most distinctive attributes of the compound can not be found in the elements taken separately, but only after the interaction has actually occurred. We must not fail to consider the long period of Darwin's strict "self-activity" in collecting evidence, pro and con, bearing on his hypothesis ; and the activity designed, notice, to ascertain whether or not there is a process going on in the outer world of plants and animals corresponding to the Psychic Integration process he had conceived, i.e., had pictured in his "inner world" of consciousness. The genuineness of the individual, the personal, the unique character of mental life and mental creation can hardly be more strikingly illustrated than by such cases as this of Darwin's when the conception, the hy- pothesis, is kept to one's self so long in order "to prove" whether it is "true" or not. Now I want to call particular attention to the indubitable fact that these illustrations are only extreme manifesta- tions of attributes which are universal in the human animal at least. There is no normal human known to anthropology which has not some measure, no matter how small, of creative impulse in art and in science. As a conclusion to this presentation of instances I must again insist upon one of my cardinal points : that the in- dividually active and creative power of the human organism on its psychical side is not a whit less real, less objective, less a natural phenomenon to the natural historian than is the individually creative power of physical growth and variation, and reflex and tropistic action. Indeed, the thorough-going, consistent zoological naturalist, the substance of whose science is largely animal behavior in all its aspects, can not possibly approve the effort to separate completely the two sorts of creation. First Move Toward Showing the Organismal Character of the Higher Psychic Life Now for the further scrutiny of such psychical facts as those typified by the examples presented, for the pur- pose of seeing what has been done and may yet be done to- ward bringing them into accord with the organismal con- ception, the pole star of all our previous discussions. This examination will begin, as others have begun, by showing how elementalistic attempts to interpret organic phenom- The Unity of the Organism cna soon reveal their inadequacy and finally break down as the efforts come to face the increasing complexity which progress of objective research always finds in such phenom- ena. Associationist Psychology a Special Case of Element alist Biology In the particular psychical realm we are now to examine, elementalist theory has appeared most prominently as what is called Associationism. This flourished first in England as the school of English Associationists, David Hartley, near the middle of the eighteenth century, being usually consid- ered its founder. Psychologists of this group hold that ideas, which for them appear to be identical with sensations, are the "ultimate elements" of psychic phenomena. "Ac- cording to this theory, rigidly carried out, all genesis of new products is due to the combination of pre-existing ele- ments." Even the passions, according to Hartley "must be aggregates of the ideas, or traces of the sensible pleas- ures and pains ; which ideas make up, by their number and mutual influence upon one another, for the faintness and transitory nature of each singly taken." The "piling up of fancy upon fancy, of jest upon jest, the long embel- lishment of humor and foolery and horseplay" which Pro- fessor Manly shows characterize many of the Shakespearian plays, would be explained, according to this kind of psy- chology, not really by the author Shakespeare but by the "aggregation," in some way, within him of ideas. And, similarly, the works which in popular language are said to be by a Darwin, a Humboldt, a Copernicus, an Aris- totle, are in reality not by but merely m these men. The men were only the places of aggregation of the elements — the ultimates — by which the teaching on the origin of species, on the general character of the earth, on the solar system, Psychic Integration on the deeper meaning of external nature, were produced. Again the old story with which we have become familiar: not the organism, but elements of, or perhaps merely in it, are the causal explanation of whatever occurrences are associ- ated with the organism. It is, I think, safe to assume that both the merits and the demerits of associationist psychol- ogy have been made patent enough, at least to English- speaking students, by the writings of James and others. If only the doctrine of "association of ideas" can be satis- fied to do what it is really able to do, and not insist upon trying to do what it can not do, its usefulness is great and its permanence in psychology assured. As indicated above, the "huge error," as James expresses it, by which the "whole historic doctrine of psychological association is tainted" ' is only another miscarriage of the elementalist mode of reasoning, and so is subject to the general type of criticism which the reader has met in every chapter in this book. In order to divest the criticism as much as possible of personal flavor I shall make large use of James' language. "All these writers," says James, referring to Hobbes, Hume, Priestley, Hodgson and the later English associationists, "hold more or less explicitly to the notion of atomistic 'ideas' which occur. In Germany, the same mythological suppo- sition has been more radically grasped, and carried out to a still more logical, if more repulsive, extreme, by Herbart and his followers, who until recently may be said to have reigned supreme in their native country." Now the objection to the doctrine of "atomistic ideas" does not so much concern the conception of ideas as atoms as the nature attributed to these atoms, namely in assum- ing them to be immutable, and sufficient in their isolate capacities to account for the thought and other products arising from their "association." The following two quota- tions illustrate the form this criticism, the essence of which 230 The Unity of the Organism is now very familiar to us as biologists, takes when it ap- pears in garments of a psychologist's making. The "huge error" of the association doctrine, mentioned above, James explains, is "that of the construction of our thoughts out of the compounding of themselves together of immutable and incessantly recurring 'simple ideas.' If there be any doubt as to the meaning of this surpris- ingly un-James-like wording, there certainly can not be as to the following: "For Herbart each idea is a permanently existing entity, the entrance whereof into consciousness is but an accidental determination of its being. So far as it succeeds in occupying the theatre of consciousness, it crowds out another idea previously there. . . . The ingenuity with which most special cases of association are formulated in this mechanical language of struggle and inhibition, is great, and surpasses in analytic thoroughness anything that has been done by the British school. This, howrever, is a doubt- ful merit, in a case where the elements dealt with are arti- ficial ; and I must confess that to my mind there is something almost hideous in the glib Herbartian jargon about Vorstel- lungsmassen and their Hemmungen and Hemmungssummen, and striken and erheben and schweben, and Verschmelzungen and Complexionen." ll The long and short of the "huge error" of associationist psychology is that ideas are no such independent, immutable, simple entities as the doctrine supposes ; that in their origin and in all they are, and all they do, and all that comes forth from their association, they are in some sort and measure dependent upon — what? Something. Search after this something has been a large motive of more recent psycho- logical inquiry. One way of supplementing and rectifying associationist doctrines is to epitomize the shortcoming of these doctrines in the statement that they recognize only the objective side of the association process, whereas the subjective side is Psychic Integration equally important. Thus Pillsbury : "It was a neglect of the subjective conditions and the insistence upon the objec- tive side of the problem that has led the English Associa- tional School into disrepute. The explanations that they gave were true as far as they went, but their incompleteness vitiated the conclusions as soon as they laid claim to uni- versality." And the author then shows, convincingly enough, how two sets of subjective factors, attention and choice, play a large and important role in determining the "associative train." And further, "A complete explanation of association demands that both sets of factors [objective and subjective] be taken into account; to omit either is to fail in the solution of the problem." Preliminary Examination of Objective and Subjective There is undoubtedly a real gain in having proved, as Pillsbury and others surely have, that a "side" other than the objective in association does exist. It is highly ad- vantageous, also, to have learned enough about this other "side" to make the term subjective an appropriate name for it. But any one coming to a study of the associational activities of the organism's psychic life as we have, namely as naturalists, can not avoid, if true to his traditions and methods, wanting to know how these two "sides," the objec- tive and the subjective, go together — what the nature is of their relation. For the very fact that they are two sides of one thing is to the naturalist prima facie evidence that they are in vital organic connection. Even the two sides of an inanimate thing, like the earth with its two hemispheres, have a relation to each other too important for the earth sciences to ignore or even to put off as merely "parallel." But when it comes to an entity like a live animal, the quin- tessence of which is organization, the question of how two of its "sides" so important as its objective and its subjec- The Unity of the Organism tive are related, becomes most fundamental, especially when a subject like that of psychical association is up for con- sideration. It is, then, fundamental to our enterprise to find out all we can about the connection between the objective and sub- jective aspects or sides of the organism. It would be folly to expect results of any value from an effort of this sort without having first given attention to the nature of each of the sides. Now the objective "side" comes to much the same thing as the physical or material organism as we are conceiving the "sides." But since this has been the sub- ject of our whole treatise up to the last two chapters, and even of the greater part of these, we are already possessed of enough understanding of this "side" for our present purpose. As to the subjective "side" the case is different. Into its nature, its makeup and activities, we have looked very little — only in a bird's-eye-view fashion thus far in the present chapter, and into its marginal or transitional zone in the preceding two chapters. We are, consequently, obliged to penetrate further into the subjective realm itself before the main problem, that of the relation between the sides, is attacked. The Essence of Wundtian Apperception This carries us back to the point at which we brought Royce's suggestion of a relation between Loeb's tropism theory and Wundt's apperception theory into the discus- sion, the return to this point being for the purpose of using Wundt's conception to induct us further into the nature of mental life. The importance of examining Wundt's con- ception is two-fold. In the first place, we want to know whether or not it is genuinely descriptive of man's highest psychical life. If it is, nothing can stand in the way of its Psychic Integration 233 acceptance, so far, by the anthropological zoologist. But in the second place we must know whether or not it carries, as some critics believe it does, transcendental or supernatural- istic implications. If this charge be true it is of course to this extent unsanctionable from our standpoint. Wundt's most concise characterization of apperception which I have found is, "The process by which any content of consciousness is brought to clear comprehension we call apperception." A content of consciousness is any definable experience we may have. All consciousness whatever is consciousness of something or other. This "something or other," no matter what, nor whether regarded as a whole or in part, is a con- tent of consciousness, according to my understanding. What is most distinctive about Wundt's characterization may be regarded as centering around the word clear. When a particular content gets itself into the lime-light of con- sciousness— when it becomes the center of attention — the process by which it does so is apperception. On the other hand, the process by which contents, though brought into consciousness, come only into its outer zones or edges, and do not monopolize attention, is perception. Though this getting of a content into clearness in consciousness, this monopolizing of attention, may take place passively or actively so far as the mind as a whole is concerned, the ac- tive way seems to be the more distinctive and important, at least for mental life as a whole. It is apparently this positive activity of apperception, directed toward making particular contents of conscious- ness clear, which has brought criticism upon Wundt's con- ception. "Wundt talks," says Pillsbury, "almost as if there were a faculty or force of apperception, something behind and superior to consciousness, which brings about the change in clearness of the impressions. There is in the brain a definite centre of apperception, and in conscious- 234 The Unity of the Organism ness a force very closely related to will, that in and of itself chooses certain ideas for elevation to the high places of consciousness, and equally arbitrarily rejects others." And then follows this in Pillsbury's criticism, which brings out unmistakably its real purport: "It is very much like the self-conscious unity of apperception of Kant, which gives the final form and order to the various disconnected elements of the mind, and is in so far something inexplicable, a factor in experience that must be assumed without any further discussion of its nature, origin, or laws of action." 15 A suspicion, obviously, that the transcendentalism of Kant broods over Wundt's theory. As to the justification of this suspicion we need not be concerned here. Enough for us at this point to recognize that from the standpoint of description as natural history practices the art, or aims to practice it, Wundt's account of the way the mind works in a vast range of its activities seems true, and as far as it goes is satisfactory. Not only the matter of clearness of the contents of con- sciousness, but their makeup as well is important. Al- though "psychical elements" figure largely in Wundt's sys- tem, one finds no intimation that the whole mind and its contents can be "explained" by reducing them to "ultimate elements" after the familiar manner of elementalist explana- tion. "All the contents of psychical experience," Wundt says, "are of a composite character." And it follows from this that "psychical elements, or the absolutely simple and irreducible components of psychical phenomena, are the products of analysis and abstraction." The two words, "analysis" and "abstraction," need par- ticular consideration. The psychical elements found by analysis do not exist, as such, in nature. Analysis, in this case, is logical or thought-analysis, and not objective analy- sis. We should do well to recall what was said in the dis- cussion of reflexes, namely that the "simple reflex," though Psychic Integration 235 legitimate and useful as an aid to interpreting the phenom- ena of reflex nerve action, has no actual existence in nature. It, like the "psychical element," is an abstraction. This is only another way of saying that psychical elements are what they are because they are parts of the mind as a whole, just as we have seen over and over again physical elements of the body are what they are because they are parts of the body. "The specific character of a given psychical process depends for the most part not on the nature of its elements so much as on their union into a composite psychical com- pound. Thus, the idea of an extended body or a rhythm, are all specific forms of psychical experience. But their charac- ter as such is as little determined by their sensational and af- fective elements as are the chemical properties of a compound body by the properties of its chemical elements. Specific char- acter and elementary nature of psychical processes are, ac- cordingly, two entirely different concepts." We must not miss an essential point in this, that since with psychical elements just as with chemical elements we never know exactly what or how much each particular ele- ment contributes to the compound, we are obliged to con- ceive the attributes of the compounds as pertaining to the elements collectively even before the compounding has been done. So it comes about that because all contents of conscious- ness are fundamentally composite, but are also resolvable into components of various grades of complexity, synthesis and analysis have a prominent place in the Wundtian system. Of these, synthesis is the more definitive and fundamental, since it enters into the very nature of consciousness itself. Consciousness is, according to Wundt, the :