**»■ A, ^'i'--^^^^-r"^.^-' a: Spirazines 33 Purine derivatives In situ. a Flo. S'a N I C Y' \ %• ^h. 34 Spikazines chemical explanation of all phases of vital activ- ity will soon be forthcoming. Evidence of direct connections between the amino groups of one spiral and the carbonyl groups of an adjacent spiral is furnished by the urea and guanidine groups which occur in the pyrimidine and purine derivatives and in argi- nine and creatine respectively. When protoplas- mic structures are subjected to severe stresses, as must occur in the nuclear material during cell division, we would expect the hexagonal compart- ments to become flattened by lateral compression in one direction or another so as to bring the amino groups of one spiral directly against the carbonyl groups of another spiral, whereupon the amino hydrogen will combine with the carbonyl oxygen to form water and leave the carbonyl car- bon atom of one spiral connected directly to one or two nitrogen atoms of an adjacent spiral as illustrated in Figs. 4 and 5. Since the carbonyl carbon atom is already connected to the nitrogen atom immediately adjacent to it in the same spiral, we will have produced in this manner either the urea or the guanidine complexes which occur so extensively in the products of both plant and animal metabolism. A connection between one carbon atom and two nitrogen atoms may also occur at the positive end of a single spiral Spirazines 35 as illustrated in Figs. 4a and 5a. The formation of substances like arginine and uric acid may thus be accounted for in several different ways as shown in the accompanying diagrams. In the nucleated cells of plants and animals these urea and guanidine complexes occur princi- pally in the chromatin material of the chromo- somes. This chromatin material has a strong affinity for dyes so that it stands out very promi- nently in stained preparations, but the fact that it is conspicuous in appearance does not prove that it plays an important part in vital processes. If purine derivatives are formed in the manner suggested in the preceding diagrams, then it appears that the chromatin material of the nucleus, which has generally been regarded as the seat of heredity, is actually nothing more than an accumulation of waste material. It is a significant fact that after cell division is complete, the chromatin material spreads out into irregular patches over ths surface of the nucleus and is probably absorbed by the cyto- plasm while a new set of chromosomes develops in the interior of the nucleus. In order to ex- plain the supposed genetic continuity of this chromatin material it has usually been assumed, although not supported by a trace of experi- mental evidence, that at least a portion of it is 36 Spieazines transmitted to the new chromosomes that are being formed within the nucleus. The spirazine hypothesis, on the other hand, teaches that the seat of heredity must always consist of a coordi- nated system of spirazines, and that the urea and guanidine derivatives which may at times be lib- erated by certain configurations of spirazines in the nucleus can serve only as chemical messengers or intracellular hormones by means of which the various configurations of spirazines in the nu- cleus can exert their specific influences upon the other portions of the cell. It appears from the spirazine hypothesis that heredity takes place in two different ways. The inheritance of major characteristics, such as the arrangements of the various tissues and organs by which the larger groups of plants and animals are distinguished from one another, is probably determined directly by the cross-sectional pattern of the nuclear spirazine structures and would not be subject to MendePs laws; whereas the inheritance of minor or modifying characteristics, such as the colors or textures of tissues or organs already present, is probably determined by substances in a dis- persed or molecular state which have been liber- ated by the nuclear spirazine structures, and the inheritance of such minor characteristics would be governed by Mendel's laws. Spirazines 37 In the accompanying diagrams it has been pos- sible to represent the molecular structure of liv- ing matter only in its statical aspect, but it should be constantly borne in mind that the various units of living matter are not rigid crystalline structures but are plastic molecular fabrics which are almost continually in a state of metamorpho- sis and that it is the specific behavior of living matter and not its exact form or appearance which is carried on through successive genera- tions. It is impossible to represent adequately on paper the various deformations of which the spirazine structure is capable, but it should be noted that besides mere flattening of the polygo- nal compartments in one direction or another as represented in Figs. 4 and 5, there is also the pos- sibility of longitudinal straightening out of the spirals themselves, which can take place without the disruption of either the peptide linkings or the connecting complexes at the triple junctions, so that almost every conceivable change of shape is possible with these molecular structures with- out any mutilation of the pattern which is charac- teristic of the species. 38 Spirazines Fi^. 6. Transverse section showing diaqrammcitically the prohahle moieculat structure of the simplest form of life* THE SIMPLEST FORM OF LIFE Hypotheses concerning the origin and constitu- tion of the simplest living organisms must neces- sarily be surrounded by a great deal of uncer- tainty, but any hypothesis, however speculative, is preferable to total darkness. Although life must have commenced by the formation of single polypeptide spirals, yet it could not have existed in any sort of a stable and self-perpetuating form until a number of such spirals had clustered together into parallel for- mation and had become permanently joined to one another. It does not appear that a series of polypeptide spirals connected edge to edge to form a single polygonal compartment could con- stitute a permanent living organism because the exposed corners would render such a structure extremely vulnerable. Structures of this sort were probably formed temporarily when life first emerged from inorganic substances, but they must have become reinforced inmaediately by the addition of more spirals. If we assume that there was first formed a single hexagonal compartment, and that an additional hexagonal compartment was then formed upon each of the sides of the original one, there would have been produced a cluster of seven compartments which would be 39 40 Spieazines considerably more stable than a single compart- ment because there would not be more than two exposed corners on any one of the seven compart- ments. It is doubtful, however, whether even a structure of seven compartments could exist per- manently because the two exposed corners on every peripheral hexagon would constitute re- gions of weakness, whereas if we would substitute pentagons for hexagons at the periphery then there would be too much straining of the triple junctions. If, however, this structure would become sur- rounded with another layer of hexagonal com- partments it would be rendered considerably more stable because only the alternate compart- ments at the periphery would then have two ex- posed corners and the remaining compartments only one, and if the compartments with two ex- posed corners be changed over into pentagons then none of them will have more than one ex- posed corner. Since each peripheral polygon now occupies only one-twelfth of the entire circumfer- ence, it appears that conditions at the periphery will not be materially changed by the addition of more layers of compartments. A cluster of nine- teen polygonal compartments arranged as shown in Fig. 6 should therefore possess as much stabil- ity as any larger structure and probably repre- sents the simplest form of life. THE CAUSE OF CELL DIVISION Every living organism exhibits during some period of its existence the phenomenon of cell division, which may take place either by simple fission as in the case of bacteria, by budding as in the case of yeasts, by direct amitotic division of the nucleus as in the case of pathological growths or tissues of a transcient nature, or by mitotic division of the chromosomes either with or with- out the formation of centrosomes and asters as in the case of nearly all higher plants and animals. The process is always entirely spontaneous, so that it must be the result of internal and not of external forces. It has been suggested that cell division might be due to the fact that as an organism grows larger there will be a point reached where it will become physically unstable, due to the fact that its mass, Avhich contributes to its instability, in- creases as the third power of its linear dimen- sions, whereas its surface, which by reason of its surface tension contributes to its stability, in- creases only as the second power of its linear dimensions. Such an explanation is inadequate because the mere presence of a large mass or volume would not cause an object to divide into fragments unless it be acted upon by external 41 42 Spirazines forces, and it has never been shown that physical disturbance is necessary for cell division. Cell division cannot be attributed to surface tension because the eifect of surface tension is always to hold a body together and never to sepa- rate it into fragments, but even if surface tension would act in the opposite direction from that in which it actually does act it would still be insuf- ficient to account for cell division because the cohesive strength of protoplasmic fibers is far greater than any force that could possibly result from surface tension. Another suggestion has been that cell division might be due to the fact that as an organism be- comes larger its food requirements increase with the third power of its linear dimensions whereas the quantity of food within reach increases only as the first or second power. This explanation is also inadequate because shortage of food would only cause an organism to become under-nour- ished, which might retard its growth and eventu- ally result in its death, but would not cause it to divide. Attempts to explain cell division on the basis of food economy have been due to a confu- sion of the principles of phylogeny with the prin- ciples of ontology. Numerous other hypotheses have been pro- posed, but they have all been found untenable for Spirazines 43 Mechahical U/usttatioh of Celt Division Fig. 7c(^ r/^. 7^' 44 Spikazines one reason or another. A more complete account of them will be found in E. B. Wilson's book on *^The Cell in Development and Heredity.'' It appears that spontaneous cell division can be explained only on the basis of a heterogeneous internal structure, such as is postulated by the spirazine hypothesis. In order to convey as clear a conception as possible of the underlying princi- ples, a mechanical illustration will be used. In Fig. 7a two clamps are applied to a rope and their ends forced apart by means of jack screws. Let us assmue that each screw is able to exert a force of one gram, but that it takes three grams to tear the rope. The structure in Fig. 7a will therefore not divide of its own accord. Let us now add to each end of this structure another rope clamp and another pair of jack screws as shown in Fig. 7b, these additional parts being identical with the homologous parts of the original structure. Each time when such additional units are added to the ends of this structure the tension of the rope is increased, so that eventually it will tear in two at the center. If, now, Ave substitute a polypeptide spiral for the rope, and double or triple junctions for the clamps and jack screws, then we will have conditions substantially as they exist in bacteria or other simple forms of living matter. Growth by assimilation of additional amino acid mole- Spieazines 45 cules will continue endwise, and if the connecting complexes are of the proper kind their mutual repulsion will eventually become sufficient to overpower the cohesive forces of the spirals them- selves so that after the organism becomes of a certain length it will spontaneously divide into two halves without the intervention of any exter- nal forces. Cell division may also be attributed to a differ- ence in molecular structure between the outer portions and the interiors of the bacteria, chro- mosomes, or other elementary units of living matter. As has already been explained, the outer portions probably contain many double junctions with pairs of sulphur atoms in the places of the gamma carbon atoms, whereas the interiors must be composed mostly of triple junctions. It is highly improbable that two such radically differ- ent structures would occupy exactly equal vol- umes, and since the surface layers are incapable of shifting longitudinally upon the interior struc- tures there will be a gradual increase in tension of the less voluminous structure as the organism grows in length, so that eventually it will become torn in two. This process is clearly illustrated by cell division of a bacillus. If the internal struc- tures are more voluminous than the surface struc- tures, cell division will begin by the formation of 46 Spirazines a circumferential groove and will result in the production of daughter cells with rounded ends. However, if the surface structures are the more voluminous, then the interior portions will sepa- rate first and leave the daughter cells with con- cave ends. Although a heterogeneous internal structure is always necessary for spontaneous cell division, yet the specific manner in which it is brought about need not always be the same. A single cell may contain as many as three different kinds of self-perpetuating bodies, namely the nuclear structures (chromosomes), the central bodies (centrosomes and asters), and the plastids (leucoplasts and chloroplasts). These three are so different from one another in their structures and behaviors that it would hardly seem possible for all of them to undergo cell division by the same specific method. The nuclear structures and the plastids probably divide as the result of internal stresses which may be produced in vari- ous ways as has already been explained, but division of the central bodies is probably due to entirely different causes. A central body consists of a radiating cluster of protoplasmic fibers called the aster, which appears to grow from a tiny central region called the centrosome. Central bodies sometimes ap- Spirazines 47 pear to be formed de novo from cytoplasmic material and usually occur in pairs, although four or more may occur in a single cell. A constant circulation of fluid is maintained inwardly through the astral rays and outwardly through the spaces between the rays, which is probably the means employed for gathering food material for growth. The clustering of the astral rays about common centers may be due to conditions similar to those which cause the molecules of a polar solute to arrange themselves with the same ends toward the solution. As these astral rays grow longer and become more numerous they will become more crowded in the region of the centrosome, so that the entire structure will eventually become unstable, will cave in, and two separate centro- somes will make their appearance. The rays from these two daughter centrosomes will tend to spread out in all directions and as a result of their mutual encounters will cause the two new asters to move away from each other and towards the opposite sides of the cell. f^f^ -*^-^ f^^^ t t B « A R YJSGJ •^.<.. ^A»*-^^. "Ov ^ vs THE SELF-CONSCIOUS MIND A discussion of psychical matters in a treatise on biochemistry may seem frivolous at first glance, but when we consider what a close and in- separable relationship there exists between mind and living matter, and what a powerful governing action the mind has over the body, then it would seem to be not only pertinent, but in fact neces- sary in a treatise of this character to give the mental factor full consideration. The mind functions in three different ways. It gives us sense perceptions, it forms the medium for thought and memory, and it enables us to act voluntarily through the exercise of our free will. There is no satisfactory evidence to show that mind is a separate entit}^ capable of existing in- dependently of living matter, or that it can reach out and act beyond those molecular structures in which it originates. It cannot be a substance because it does not possess any of the properties by which substances are recognized. Neither can it be a vibration, or, in fact, any form of energy because it will produce no effect upon even the most delicate of physical instruments. Although many fantastic ideas prevail as to the intrinsic nature of the mind, yet if we confine our- 48 Spirazines 49 selves strictly to the evidence presented by known and demonstrable facts, then we must regard mind not as a self-sustaining entity, but rather as a property or attribute of living matter. Mind is synonymous with self-consciousness because whatever can be said of the mind can also be said of the self-consciousness. Without mind or self-consciousness we can have neither sensa- tion, thought, memory, or volition. The individual self-consciousness is coexten- sive with the central nervous system. Most of the cells of our bodies form parts of us physiologi- cally but not mentally. In order for a cell to form part of us physiologically it is only necessary for the cell as a whole to be definitely coordinated in position and specifically related in function to the other cells of the body, but in order to form part of us mentally it must be coordinated with the cells of the central nervous system on a molecular scale, that is, its individual spirazines must be coordinated with or joined to those of our central nervous system in a specific manner, so that elec- tric impulses passing along a certain spiral or polygonal compartment of on^ of these cells will be transmitted to a certain spiral or polygonal compartment of the other instead of being dissi- pated and lost in the surrounding protoplasm. 50 Spirazines Thought and memory may be explained on the theory that a previous impulse from a sensory nerve has produced such a forceful coordination of certain of the spirazines of the cerebral cortex that the surrounding structures have become per- manently modified in such a manner that they will retain the spirazines in their new positions for some time thereafter. Free will and volition are probably due to the spontaneous activity of the spirazines in our cerebral cortex and differ from memory only in that the electric impulses which are produced by such activity have found an outlet through the motor nerves instead of being confined to the molecular structures of the cerebral cortex. Whether the exercise of free will involves any violation of the laws of nature is a question on which there is much difference of opinion. Ac- cording to the laws of nature the behavior of every physico-chemical system is fixed and pre- determined, whereas the exercise of free will in- troduces an arbitrary and indeterminate factor. Since there cannot be two independent systems of governing forces operating in the same place and at the same time, we must either regard free will as a delusion, or we must assume that living mat- ter does not come under the domain of those nat- ural laws which govern physico-chemical systems. Spieazines 51 The existence of free will is being made known to us directly through our self-consciousness, and it would be very dogmatic and unscientific for us to reject the testimony of our self-consciousness in so far as it furnishes us with a basis for our belief in free will, but yet to accept it in so far as it informs us of the operation of the laws of nature. The classical principles of mechanics, electro- dynamics, and thermodynamics, which seem to signify predetermination to the exclusion of free will, were derived from experiments upon iso- lated physico-chemical systems and deal only with the effects of simple elementary forces or with the combined or average effects of large numbers of atoms or molecules. There is no arti- ficial device known which will respond to the specific behavior of a single selected atom. Even the streaks produced in supersaturated vapor by the individual alpha and beta particles of radio- active substances constitute no exception to this rule, for what is really being observed here is only the presence of a particle and not the spe- cific behavior thereof. It is only through the medium of living matter that the individual behaviors of the various atoms can make themselves known to us. In the molecular structure of living matter the various atoms are coordinated and connected with one 52 Spirazines another in a specific manner so that the relation of each atom to the structure as a whole is differ- ent from that of any other atom. In chemically organized structures of this sort the specific effect of each atom will be transmitted along the spirazines of the protoplasmic fibers to other parts of the cell, just like the specific effect of each atom of a molecule is transmitted to other parts of the latter. An individual atom may therefore ex- cite a nerve or other protoplasmic fiber in such a manner as to produce a response of which we may become aware. Such responses may manifest themselves either as thoughts, sensations, or voli- tions and will not conform to any of the laws of nature by which the world about us is governed but will appear to us as entirely arbitrary and without natural causation, although they may actually have been predetermined by intra-atomic conditions which are beyond the reach of physico- chemical methods of exploration. Predetermina- tion by natural law ends where atomic structure begins, because w^e cannot extend the laws of nature by analogy into realms where conditions are not the same as those under which such laws were derived. The arbitrary behavior of living matter affects primarily the second law of thermodynamics be- cause this law applies only to systems in which the variable components are capable of approach- Spirazines 53 ing a random state of distribution, whereas in the molecular structure of living matter the orderly arrangement of the atoms along the sides of the polygonal compartments will tend to sort out rather than mix up the molecules or ions within them. The passageways through these polygonal compartments are only about ten Angstrom units in width, which is not sufficient to permit any free flow of fluid therethrough. Since the spirazines which form the walls of these compartments are polar structures, they will render the electric fields within such compartments unsymmetrical so as to facilitate the migration of molecules or ions in one direction but retard them in the opposite direction. The direction of migration of molecules or ions through these compartments may also be con- trolled by side chains extending inwardly from the walls thereof and functioning in a manner similar to check valves. These side chains may be in the form of fat or carbohydrate molecules in the process of formation which have not yet become detached. Since they consist of only sin- gle chains of atoms they will be sufficiently sensi- tive to respond to the approach of individual molecules or ions, and like Maxwell's demons will close or open the passageways through the polyg- onal compartments according to whether a certain ion or molecule approaches from one direction or from the other. 54 Spikazines In either case the effect will be a sorting out of different kinds of molecules or ions from one an- other or an accumulation of molecules or ions of the same kind so as to build up osmotic or hydro- static pressures or electric potentials. These processes will take place in contravention to the second law of thermodynamics because the energy which is thus rendered available will not have been obtained entirely from the oxidation of food material but partly from the heat of the sur- roundings. Vital energy of this sort should not be con- fused with vital force, for the two have nothing in common. The principle of vital energy is entirely consistent with the laws of nature and supple- ments rather than contradicts them, whereas the doctrine of vital force assumes the existence of some mysterious power which is supposed to act in contravention to the laws of nature to control such processes as metabolism, growth, and repro- duction. Vital energy is within the realm of the comprehensible and the possible existence of such a form of energy has been suggested by physicists long before the conception of the spirazine hypothesis, whereas vital force is supposed to be something which is incomprehensible to the human mind, and the existence of which would be contrary to all the principles of science.