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Cells and Yin-Yang polarity- (Towards greater similarity between the animate and the inanimate) ML Kothari, Lopa A MehtaDepartment of Anatomy, Seth G.S.Medical College, Bombay 400012, India
Correspondence Address: Source of Support: None, Conflict of Interest: None PMID: 731611
A cell-plant or animal-is proving a bioelectric wonder already boasting of pyro-, piezo-, ferroelectricity, solid state and electretism as eminent exhibits and probable functional mechanisms. A cell, its parts, and its products owe the bioelectric boon to inherent and universal polarity pregnant with dipolar electromagnetic moment.
"The ultimate goal of all science is to devise and explain conceptual schemes about the nature of the universe in which we live. The more we learn of this nature the more we detect a basic unity in all science." [25] The latter generalization in the foregoing is all the more vindicated by recent findings that reveal each cell-animal or plant-to be endowed, in its nooks and corners, with polarity that was hitherto obtained in physics only; the polarity endows the cell with electromagnetism that Einstein [1] found as an all-pervading fundamental physical reality to which also the cell responds in varied manners. [4],[39] This paper is an attempt at presenting a multidisciplinary synthesis that promises a better comprehension of cell structure and function.
A living cell defies definition. As an acronym, CELL could read Cytologic Embodiment of a Law called Life, or Coordinated Energy-ensemble Labelled Life. With the prominence gained by DNA -"the most celebrated chemical of our time "[19] -a cell is rightly called a biochemical wonder. Recent insights into the electrical activities going on in a cell suggest it being a bioelectric wonder, too. Lowenhaupt [28] at a recent symposium on "Electrically Mediated Growth Mechanisms in Living Systems," generalised that "the electricity of a living cell is at the essence of its life," subserving such diverse functions, [2],[28],[29] as cell growth, cell differentiation, intercellular communication, wound healing, hormone actions, muscle tone, vision, other forms of sensory reception, photosynthesis, antibiotic action, the engram, cyclosis, and so on. Cells (plant or animal), their components including DNA, cell products such as cellulose, glucose, cholesterol, collagen, keratin and chitin, and tissues such as bone, tendon, nerves manifest, in varying degrees, piezoelectricity, pyroelectricity, ferroelectricity, solid state and electretism. [2],[3] Athenstaedt [2] pointed out why the recognition of such forms of bioelectricity was delayed: "The fact that the existence of this material property (of pyroelectricity) was generally assumed to require a crystalline pattern may explain why it was detected in organic structures at such a late stage." Similarly, as Gross [21] remarked, "the strange behavior of electrets revealed by the early experiments,, reinforced by Gemant's view that for theoretical reasons `they should not exist,' did much to shroud the electret effect in mystery." It hi now being appreciated that living systems possess electromagnetic sensitivities "several orders of magnitude greater than predictable by present concepts of cellular or organismal physiology." [4] Lerchenthal, [27] emphasized the gross conceptual and instrumental limitations of modern physics when it comes to measuring the intracellular events: "Even the finest available electrodes have diameters of about 1µm. This seems much worse than a sledge hammer and a fine wristwatch, because this diameter (1 µm) is many thousand times larger than atomic distances, which indeed is the level on which biologic systems operate." The potential gradient between two points, within a cell or a collagen molecule, may be thousands of volts per centimeter, not because the voltage is high, but because the distance is in angstroms. [18],[27] But such phenomena are extremely difficult to analyse by most techniques. [11],[27] Bioelectricity, a giant of the future, is still in its infancy at conceptual and instrumental levels. Today, electrets are industrially manufactured (e.g. microphones, [21] teflon vascular grafts [21] ), and our bones have been found to be the loudest electrets. [31] The Curie brothers Jacques and Pierre discovered piezoelectricity in 1880; pyroelectricity was elucidated by Lord Kelvin in 1877, ferroelectricity in 1920 by Valasek, and the electret state was conceptualized by Heaviside in 1890 and discovered by Eguchi in 1925. [2],[21] The foregoing have been recognized as attributes of living material only as recently as 1964 and after. Yet, it seems, a great beginning has been made. Piezoelectricity the "coupling between mechanical and electrical fields" [23] - involves production of electricity by mechanical changes, while the pyroelectric effect is produced by thermal changes. In ourselves, piezoelectricity may be realized from the observation that it operates to make nerve "a lossless transmission line" [23] so that, although "nerves are such poor conductors of electric current," [30] they manage to be "such excellent transmitters of electric signals." [30] Ferroelectricity implies spontaneous electric polarization such that the polarization can be reversed by an electric field . [40] The significance of this may lie in a cell's or its component's ability to check or reverse a course of action. Solid-state is a term borrowed from electronics implying the ability of such an object to control current without the presence of moving parts, heated filaments, or vacuum gaps. [40] Solid-state could also be defined as the physical state of matter in which the constituent molecules, atoms, or ions have no translatory motion although they vibrate about the fixed positions they occupy. An electret is etymologically and functionally analogous to a magnet. "A magnet produces a static magnetic field, an electret produces a static electric field." [21] Just as we regard the magnetic field as a store of energy, [14] the electretic field is an energy store that by its effects could keep cells together, or help store and retrieve information. Bone, collagen, gelatin, DNA, cellulose and many other biopolymers behave as electrets, making it a universal property of all biopolymers. [31] Water bound to biopolymers - "bound water" - is considered of fundamental biologic importance, as it also possesses the electret state. [31],[32] Bioelectricity is a boon derived from the "inherent dipole structure" [2] of all animal and plant tissues-a universal design whereby morphologic polarity imparts inherent direction of electric polarization that gives to the warp and woof of a cell, as its milieu "electric dipole moment." [2] To name but a few structures that have been shown to be so polarized: DNA, collagen, keratin, chitin, feather, hair, teeth, bone, individual plant cells and organs, sensory receptors. At a grosser level, the human spinal cord constitutes "a permanent electric dipole over its entire length," [2] with the negative pole cranially, and the positive pole caudally. The role of erect posture, legendarily emphasized in Yoga, may be related to the polarity of the central nervous axis that is best maintained with a straight back.
The universal prevalence of polarity and bioelectricity could be taken as starting points to construct a hypothetical picture of cell structure and function. This communication presents 4 interrelated concepts: (a) CEM (CytoElectroMagnetism), (b) Polarity, (c) Pancytologism, and (d) Yin and Yang. The evidence for each of the concepts is sufficient, if not compelling.
Electricity and magnetism a la Oersted and Maxwell are two sides of the same coin. [14] Now that we know of cytoelectricity as a potent operating force, CytoElectroMagnetism or CEM becomes etymologically and conceptually comprehensible. CEM, is then, the electromagnetic effect possessed/exhibited by a cell, its components or its products, not excluding "bound water" which may be tied up to DNA or a protein. The current scientific limitation vis-a-vis detection and measurement of CEM is well brought out by Florey: [18] For purely technical reasons it is impossible to measure directly the electric potential differences between individual ions or even those between the organelles of a cell. Undoubtedly there are electric potentials, for instance, between the surface of mitochondria and the surrounding cytoplasm, but there is no recording system small enough to measure them." Florey's [18] 1966 observation warranted no alteration when Lerchenthal' restated science's present limitations in 1974. That CEM may have a lot to do has not yet hit the scientific conscious. The September 1976 issue of National Geographic carries a 42 page article on the "Awesome Worlds Within a Cell." [19] The only allusion therein to electricity is with reference to mitochondrial ATP: "ATP is the electricity of the system." Cytologic texts refer to the electrical potentials at a cell membrane, but there ends the story. Becker [4] is at pains to underscore our ignorance and indifference: "Over the past decade, there has been a growing awareness that electrical and magnetic forces have specific effects on living organisms. These effects are produced by forces of very low magnitude and are not explainable in such simplistic terms as Joule heating. They appear to indicate sensitivities on the part of living organisms several orders of magnitude greater than predictable by present concepts of cellular or organismal physiology." Becker [4] then cites a number of biophenomena mediated by electromagnetism, including the direct relationship between reversals of earth's magnetic field and the extinction of whole species in the geologic past. `Unfortunately, none of the effects are based on an adequate foundation of biological theory, and in fact, the key proposition of these effects, namely, that cells are capable of sensing and responding in a specific fashion, to levels of electric current/voltage or electrical or magnetic fields, is hardly universally accepted." [4] A brick in the conceptual foundation desired by Becker [4] could be formed by the proposition that CEM [Figure 1] is a cardinal feature that permeates the length and breadth of a cell, and that CENT operates by its field effects. The concluding para in The Evolution of Physics by Einstein and Infeld [14] bears the title "Physics and Reality", wherein the masters describe the mutation in physical thought: "The difficulties connected with the deflection of the magnetic needle, the difficulties connected with the structure of the ether, induced us to create a more subtle reality. The important invention of the electromagnetic field appears. A courageous scientific imagination was needed to realize fully that not the behaviour of bodies, but the behaviour of something between them, that is, the field, may be essential for ordering and understanding events." The concept of CEM operating by its field may be taken as a paradigm of the "courageous scientific imagination," much needed in biology. As Einstein and Infeld [14] emphasize, "The field language" dictates that "the action is determined by the field." Cybernetically speaking, CEM pregnant with EM wave with velocity "equal to the velocity of light" may account for some awe-inspiring megafeats achieved in a split second by a microminiaturization called a cel1. [14] A typical animal cell-"each cell a better chemist and physicist than all the Nobel prize laureates put together" [36] - is a micro-universe brimming with 200 trillion molecules [19] comprising discrete pieces of life "each performing with exquisite precision, and often in thousandths of a second. "[19] The cell's master choreo, grapher DNA operates its over 100,000 genes in a mass no greater than 0.00000000001 (10 -11 ) gm by acting as an "information tape" that duplicates itself, with incredible point-to-point precision, by its pair of polynucleotide chains unwinding (and simultaneously rewinding) at the rate of 10,000 revolutions per minute, the mechanism of this unwinding being entirely unknown, there being no enzymes to mediate it. [11] The genic genius of this information-tape lies in its capacity to give rise, in an almost omniscient manner, a unique individual, an Einstein, an elephant or a cancer, each unfailingly unprecedented, unparalleled, and unrepeatable. The whole tape is so compactly packed that the total human DNA would occupy a space no greater than an ice cube, but if joined end-to-end could stretch 400 times to and fro the Sun [19] (37.2 x 10 [9] miles). Surely, we are dealing with entities that necessitate concepts that transcend the intricacies and the speed of the most advanced computers. If it is the EM field that makes a computer work, it is very likely that it is CEM that makes a cell work, the way it does. Each one of us is made up of about 100 trillion cells, bound into a cooperative whole without screws, rivets, or any "demonstrable intercellular material." [11],[19] (What of a blue whale whose tongue alone is the size of a fully grown elephant, and whose cells are no larger than that of a mouse or man). And yet in this closely packed cytogalaxy, cells move ceaselessly with planetary ease and speed, during health, disease and repair. The cells do so without any pseudopodia or the space for them. It is proposed that only CEM could account for this, so to say, mobility in inseparability by variations of "attraction energy" and "repulsion energy," [5] and by polarity that keeps the myriad cells stay put. [15] Some other compelling facts are in order to drive home the conceptual imperativeness of CEM. A cell is a cold machine [30] that carries out its activities at temperature and pressure, surprisingly low in mechanistic terms, a point favouring the consideration of a cell as an electronic/electromagnetic entity. The temperature optima for unicellular and multicellular life is well below 50°C [6] Cell membrane, stronger than stainless steel, can build up a potential difference across it so much as to generate 10,000 volts as in an eel. [30] The same membrane modifies itself to form receptors that transduce and amplify varied forms of input energy into a different form of output energy, with incredible sensitivity: "The hair cells in the mammalian cochlea and the sensory cells of the lyriform organs of spiders (to mention only two examples) respond with generator potentials to vibrations, the amplitude of which is lower than the diameter of a hydrogen atom." [18] The human retina can respond to an energy input of 5 x 10 -17 watt, which at the input rate of 5 x 10 -17 watt/sec. would take 10 billion years to accumulate enough electricity to light up a 15 watt bulb for 1 second. [18] A cybernetic view of the human nervous system may suggest that the memory storage and retrieval may be occurring in it in much the same way, as in a computer. The CEM fields of dividing/ divisible cells lack permanence that the inherently non-divisible nerve cells enjoy. Looking at it the other way, nerve cells had had to be indivisible so that the structural permanence allows the recording/reading-out of information. Arthur Koestler [26] cites neurologists as claiming that only about 3 per cent of the human brain's capacity is called into use under normal circumstances. In Leonardo da Vinci or Einstein, it may be 5 or 10 percent. That makes human brain unimaginably efficient in its function, which in the current cybernetic context, sounds very much computer-like. Even if a nerve cell engrams itself by manufacturing a protein, the latter has its own electrical activity, so that the concept of CEN remains relevant.
In anatomic/biologic description, the popular descriptive term is bilateral symmetricality, a feature that allows the organism to be divided into "equivalent right and left halves." [25] But this equivalence is more an assumption than a reality In a human being, the right hand differs from the left in shape, palm-print, finger print, the right cerebrum from the left in gyri and sulci, the right eye from the left in refractive error, the right testis from the left in vasculature and position and so on. May be we are not bilaterally symmetrical, but complemental, a feature that makes its start right at the DNA/cell level, a master stroke that keeps the whole bio-world going. James Watson, [43] in his celebrated The Double Helix mentions that a starting point in his discovery of the DNA strut Lure was the realization that biologic things come in pairs. But then, in electricity also there are only two kinds of charge, and magnetic poles always occur in pairs. The electric/magnetic pairs are no way symmetrical but polar or complemental. The double helix that Watson and Crick gave to biologic thought comprises of two spirals that are in no way symmetrical, but polar or complemental. One cannot but conclude that Nature works, not only in pairs, but polar ones at that. Opposites are apposites. It has been generalized that the cell uses and may be found to be using mechanisms that are not very different from processes which are already available in the surface films of nature. If one travels backwards from the Watson-Crick pairity right down to the day DNA was conceived and formed, terrestrially or extraterrestrially [41] by Nature, one could say that She took hint from, say, magnetism wherein the north pole instantaneously induces the south pole and vice versa. The outstanding quality of one DNA spiral is to induce the complementary spiral, and this singular feature seems to account for the whole history of biology. Such complementation by DNA extended to RNA solved the problem of manufacturing proteins/enzymes, the key operators in a cell. Life delights in begetting life precisely because the existing half-life delights in inducing the other-half. Even the so-called repairing of DNA is. in fact, re-pairing as may be clear from what follows: In the "dark repair process" mediating "Repair of genetic material in living cells," the intact strand of the damaged double-stranded DNA is utilised to induce the formation of the damaged complementary strand, thus repairing itself, or more truly, re-pairing itself. [24] Hanawalt [24] generalized that "the existence of such a mechanism provides a possible explanation for the evolution of a double-stranded (redundant) form for the genetic blueprint in all living cells." Even the replication of "single-stranded" virus [30] is no exception to the above re-pairing. The "+" (plus) viral strand gets into a bacterium to induce the "-" (minus) strand, thus forming, the double-helix which then copies itself as usual. [30] The branding of double-stranded DNA as "redundant" [24] form betrays (a) the obsession that only a single strand of DNA is enough for directing RNA for protein synthesis, and (b) the lack of appreciation of the polarity/complementality that permeates a cell right up to its heart, called DNA. Does this redundancy idea mean that all the somatic cells carrying both paternal and maternal chromosomes/DNA., have triply redundant DNA, as well as redundant chromosomes, the latter redundancy being thought of, since E. coli manages with a single unpaired chromosome, and since it has almost become an article of faith that if it happens in E. coli, it must also be happening in an elephant? "For every paternal chromosome in diploid nucleus, there is usually corresponding maternal one with same form, size, and genetic function. Cell structure, function and replication become greatly clear if it is realized that the two sides-paternal and maternal-of a cell represent a fundamental polarity/ complementality, or as the Chinese would put it, the Yin-Yang halves of a cell, Yin-Yang [Figure 2] represent the eternal opposition of, and balance between the female (Yin) and the male (Yang) principles of the universe. [44] The Taoists use this symbol to represent their basic law of existence: harmony through dynamic balance of opposites. [40] "One Yin and one Yang," so generalizes Alan Watts [44] in his The Two Hands o f God, "that is the fundamental principle. The passionate union of Yin and Yang and the copulation of husband and wife is the eternal rule of the universe." Describing Yin and Yang as the polar-opposites, Watts [44] explains: "What, exactly, is polarity? It is something much more than simple duality or opposition. For to say that opposites are polar is to say much more than that they are far apart; it is to say that they are related and joined-that they are the terms, ends, or extremities of a single whole." As Lin Yutang, [46] the modern Chinese philosopher puts it, the interplay [Figure 3] of the dual forces-Yin and Yang-is "the basis of all life, all universe, and all history." The purpose of this article is to generalize that, taking, say, a human being as an example it is possible to appreciate the Yin-Yang polarity at gametic level (ovum as Yin, sperm as Yang), at the somatic cell level where throughout the cell Yin and Yang polarity prevails as best exemplified by the pairing of paternal and maternal chromosomes, and at the molecular level where the polarity of charges gives the tiniest thing in the cell a dipole moment responsible for production of CytoElectroMagnetism (CEM) to run the affairs of the cell. Before taking up Yin-Yang, however, we may profitably be through with pancytologism.
Nucleus, chromosomes and mitosis have, for too long, dominated, as terms and concepts, the cytologic scene by the reason of their compelling visibility, making many more important aspects of cell structure and function appear insignificant. "The development of cariology (nucleology) was somewhat detrimental to the study of the cell as a whole." [11] Chromosomes, representing a convenient organellar mechanism for conjugation and/or carriage during cell division, are basically functionless entities that form the most dominating feature of a "morphological event" [34] called mitosis. A functioning cell-interphase cell-shows no chromosomes, and non-dividing cells such as neurones show them never. A cell-to-divide doubles all its components during interphase-the most featureless and yet the truest, functioning state of the cell. [11],[34] The choreography of cell division (mitosis) needs the structural convenience of chromosomes that show up during metaphase. And the chromosomes just show up: "The use of the electron microscope has contributed disappointingly little to precisely those areas of cytology that were at their most developed stage during the heyday of the light microscope. The best electron micrographs of the metaphase chromosomes show only homogeneous granular masses." [30] The totally passive role of the oversung chromosomes even during the mechanical function of mitosis is piquantly expressed by Mazia [33] who parodied that "the role in mitosis of the chromosome arms, which carry most of the genetic material, may be compared with that of a corpse at the funeral; they provide the reasons for the proceedings but do not take an active part in them." Significantly enough, RNA-synthesis (indicating that a cell is functioning) stops during mitosis because condensation of chromatin as chromosomes prevents all DNA function. Nucleus, with its dominating chromosomes, is no longer the be-all and end-all of a cell, as has been thought of and taught so far. A change in cytologic thinking is discernible. The neglected Cinderella named cytoplasm is coming into its own. Teminism-cytoplasmic RNA-directed DNA synthesis in the nucleus-is a disproof of the central dogma of molecular biology that has so far been denying cytoplasm this right to direct its presumed master, the nucleus. Various mitogenic stimuli are, directly or indirectly, controlled by the cytoplasm. [22],[34],[35] During mitosis, the nuclear membrane disappears, and the nucleoplasm is continuous with the cytoplasm. [11],[34] Cytoplasm has "self-replicating" organelles-centrioles, plastids, mitochondria-that are endowed with genetic autonomy, a fact that underscores the role of the cytoplasm in transmission of the information from one cell generation to the next. [7],[11],[12],[34] Cellular differentiation involves not only the nucleus but all the cytoplasmic components as well. [7] Nuclear transplantation experiments involving transfer of nuclei from somatic cells into enucleate zygotes suggest that embryonic organizers are more likely a function of the cytoplasm rather than the nucleus. [17] Summarizing, one could say that cell structure and function can no longer be viewed in such isolationistic concepts as of nucleus, chromosomes or mitosis. A cell should be viewed as a gestalt entity exhibiting throughout its length and breadth Yin-Yang polarity, vital to its existence and function.
The assumption of Yin-Yang (female-male Eve-Adam. negative-positive. Or homologous) polarity in a cell offers explanations for such remarkable cytologic features as rapid duplicability with total fidelity (ToFi), cell differentiation and function, gametogenesis, and embryogenesis.
Loewy and Siekevitz, [30] in the epilogue to their voluminous Cell Structure and Function remark almost in Galilean style, that although we are ignorant, "yet the cell replicates with remarkable precision and predictability." The pancellular Yin-Yang polarity provides a rapid, almost automatic and precise way of duplicating a cell as unique as an individual organism. The astound ing rapidity-in a developing fetus, cells form at an average rate of 24000 per second; [37] repairing liver cells multiply as fast as the fastest liver cancer; [29] roots of rye plant grow by an aggregate length of 53 miles per day by average addition of 99,000 cells per second [38] -- is a function of Yin's ability to induce Yang and vice versa. The mitotic wave travels in a cell probably along a predetermined path, separating Yin and Yang pairs all along. Yin stays not without Yang and vice versa and the whole cell doubles itself. The double Yin and double Yang, so formed, repel each other leading to repulsion of the doubled cellular contents equally and precisely into two daughter cells, where restitution completes the formation of two individual daughter cells. The operational mechanism could be expressed as SIRRR: mitotic wave->Separation à Induction-> Replication -> Repulsion -> Restitution. The converse corollary of the SIRRR mechanism is that in the absence of the mitotic wave the juxtaposed polar-opposed Yin-Yang components exercise a restraining influence on each other providing the cell great stability and no chance for any DNA duplication. The non-dividing cell populations, also called static or perennial, may be enjoying their legendary stability against a wide variety of mutagenic/mitogenic agents due to the facts that (a) there is no cytoplasmic arrangement for the transmission of a mitotic wave, and (b) the juxtaposed Yin and Yang stabilize each other. A proof of point (a) is available from the observation that the never-dividing nerve cell nucleus readily duplicates when transplanted into suitable cytoplasm. [10] The proof of (b) is an involved one: E. coli, for example, has almost continuous and rapid replication, [11] a unicellular feature dispensed with by Nature with the emergence of a multicellular organism which, for being itself, needed the faculty of eutely [25] meaning constancy of cell number. Eutely is mediated by cell replication, but more importantly by the check on replication-a faculty enjoyed by cells that have paired chromosomes with YinYang polarity. Eutely in an organism and the diploidy of cells seem to have evolved hand in hand. As a paradigm of the SIRRR process, one could take DNA, which in a body cell is in two polar forms-maternal and paternal. Juxtaposed, they form a stable quartet of 4 DNA-helices. Separated, on passage of mitotic wave, the two maternal helices replicate, and so do the paternal, leading to a double-dose of Yin (maternal) and Yang DNA. Yin repels Yin, Yang repels Yang, accounting for the so called cytokinesis whereby a pregnant cell separates into two. As a convenience, the helices condense as chromosomes which then travel over the mitotic spindle. Brown and Bertke, [7] in their chapter on mitosis, generalize that, "all of the extant hypotheses of chromosomal motion were discussed by Schrader in 1953. Then, as now (up to 1977), there was no acceptable hypothesis to account for all chromosomal movements. But that is true of all cases of protoplasmic motion. Cells and cell organelles do move, but we cannot explain the movement, we can only describe it." Yin-Yang polarity explains this and more. It is of interest that the mitotic spindle that stretches between two centrioles (which themselves multiply in Yin-inducing-Yang fashion) has close resemblance to a magnetic field between two magnetic poles. Further, the mechanical work of splitting the chromosomes and the cell is least energy-consumptive, [11],[34] a point in favour of CEM operating. The ToFi with which cell duplication occurs is a function of my Yin inducing only my Yang, and in my kidney cell, my kidney Yin inducing only my kidney Yang. It is common knowledge that a kidney cell is one in which the kidney genotype is manifest, all the rest of it being suppressed. When a kidney cell duplicates itself, it should not happen that during the apparently chaotic process of cell-duplication, a change occurs and instead of two kidney cells, there get produced two gastric cells. With metazoism, came differentiation and with that came the need not only of a templatory mechanism but a regulatory-one too, to see that the liver cell begot liver cell and not a goblet cell, like the one lying in the adjacent intestine. With Yin and Yang together, Yin serves as a regulate for Yang and vice versa. An immediate corollary of this is that cells having only Yin (ovum) or only Yang (sperm) are neither differentiated nor can multiply. How true! The gametes are the most non-functional and non-differentiated cells that are biological dead-ends, manufacturing no protein and incapable of dividing despite being endowed with enough double-helical DNA. [7],[11] DNA, with all its genius for duplicating itself by templatory mechanism as so simplistically illustrated in textbooks, fails to replicate itself (in a gamete), being able to do so, (in somatic cells) only where it finds that a regulatory polar opposite is available.
"In the case of phenomena such as cell differentiation, we have not even begun to conceive of a productive experimental approach." [30] We know nothing about cell differentiation-"a riddle wrapped in a mystery inside an enigma" [19] --whereby our 10,000 billion cells behave in a 100 different and specific ways despite the fact that each cell, like the parental zygotic cell, enjoys the total genotype. A la Jacob and Monod, such a process is explained by "the modern but very significant aphorism that all genes do not function all the time." [7] Another way of putting it is to say that "large amounts of DNA have no apparent function. Nobody knows why it is there. What all that extra DNA is doing is one of biology's great riddles." [19] Yin-Yang concept could help. A zygote is formed by union of Yin (ovum) and Yang (sperm) cells, both of which are metabolically inert, endowed as they are with totally "inactive DNA." [7],[11] No wonder that the zygotic cell is so featureless and functionless, secreting neither, say, saliva nor secretin. The zygote primarily functions [17] to rapidly form a large bunch of like cells which after a certain number of divisions, programmedly secrete embryonic organisers that induce differentiation. The way to make a cell be a gastric or prostatic cell when it could be everything else is to make Yin and Yang DNA (derived from mother and father) create field effects [Figure 4] in the functional area (less than 5%) of the genotype. This could be done by pushing Yin and Yang apart, making them thus look rarified and invisible - a prime structural feature of functioning DNA called euchromatin. In the much larger (over 95%) remaining genotype, the Yin and Yang could be allowed to be close together, too close in fact, automatically because of mutual attraction, to obviate a field effect, and to create a compact, visible mass of DNA that is functionless and is called heterochromatin. As De Robertis et al [11] observe "heterochromatin represents condensed regions of the chromosome. Electron microscopic studies have demonstrated that it consists of chromatin fibers identical with those of the nonheterochromatic region, except that fibers in heterochromatin are more tightly folded. This property may account for some of the metabolic peculiarities of heterochromatin, particularly the absence of RNA synthesis, the genetic inertness and the late replication." This explains why cancer cells which are busy doing nothing have the highest quantity of heterochromatin that makes the nuclei hyperchromatic and pyknotic - a diagnostic feature of cancer cells that cancer pathologists and cytologists heavily rely on, but falsely so for nuclear transplantation experiments [45] strongly suggest that the malignancy of a cancer cell lies in, and is governed by the cancer cell's cytoplasm, the nucleus playing a subservient role. Differentiation thus becomes, in cells cancerous or normal, the selective synergization of Yin and Yang elements in a diploid cell. Such mechanism must be operating with ease and uniformity throughout the vertebrate phylogeny from the fishes to the ferrets making the liver cells from different species exhibit similarity-in fact, a clannish disposition. What could be the mechanism of selective Yin-Yang separation/fusion in the nucleus of a differentiated cell? (Cancer cell, too, is a differentiated cell). Cytoplasm seems the answer. It is accepted that cytoplasm, "the true internal milieu of the cell", mediates cell differentiation by controlling nuclear DNA. [7],[8],[11],[14],[22],[34],[35] The cytoplasm of thyroid cell pulls apart the nuclear Yin from Yang in the thyroid region of the genome to create functional field-effect; the rest Yin-Yang not subjected to any pulls get struck together, like the N and S poles of a magnet to form the inert but very much visible part of the nucleus. The early replication of euchromatin and the late replication of heterochromatin get explained by the fact that the former is already separated (thus sort of poised for SIRRR initiated by the mitotic wave) in contrast to the compactness of the latter. Granting cytoplasm the onus of differentiating a cell brings home the relevance of pancytologism: A cell begetting a cell in ToFi fashion must not only have the nucleus duplicating it precisely point by point, but even the cytoplasm, for it is the latter that is going to keep the nucleus "differentiated." Let us hail pancytologism and cytoplasm.
"A hen is only an egg's way of making another egg." [9] But Butler's facetious aphorism. [9] fails to convey the true story. A hen, can produce an egg, but an egg cannot reciprocate, being biologically but a dead-end. It can neither produce another egg, nor can it produce a hen (an organism) unless complemented by another biologic dead-end, a sperm. An egg that makes a hen is not an egg, but a zygote. In polar parlance, an egg is Yin (a negative cell) that must be complemented by the positive Yang before anything can happen.
In 1892, the need for meiosis (halving of chromosomes) in gametogenesis was intuitively theorized - "a postulate that was quickly confirmed cytologically by others". [25] But gametogenesis is not mere halving of a cell or its chromosomes, but the production of polar opposite cells: "Rather typically, the gametes that unite are somewhat different from one another .... the extreme contrast (is) of sperm and ova." [7] And these cells, although a great contrast one from another, have a pristine powerful affinity for each other - reminiscent of Yin's love for and dependence on Yang, and vice versa. Introduction of a microneedle between the two pronuclei of a recently fertilized egg, revealed that the two pronuclei acted as if attempting to overcome the resistance and complete the conjugation. [7],[11] The generalization that the "formation of gametes is more widespread than even sexuality" [7] more than emphasizes the indispensability of gametes in the genesis of metazoic organisms. At unicellular levels too, polarity exists as exhibited by the plus and minus strains of some algae, fungi, and protozoa. [7] Even a plus strand virus getting into a bacterium, first gets for itself a minus strand, and the two together, constituting Yin with Yang, as it were, multiply. The host bacterium eventually releases only the plus strand to the outside. [30] This viral phenomenon most cogently illustrates what happens at the, say, human level: A sperm (plus gamete) meets an ovum (minus gamete), and the two put together form the adult male which then releases only the plus cells - sperms. If the adult is a female, only the minus cells are released - ova. Butler could be paraphrased to say that an egg meets a sperm to produce a hen or cock to get once again an ovum or a sperm.
An ovum and a sperm are more important than the sexes they represent. If in mammals and drosophila, it is the sperm that determines the sex of the offsprings, it is the ovum that dictates this in birds, reptiles and fishes. [11] In bees, it is the sperm that makes a female, the unspermed egg producing a male. [25] Further during the meiotic conjugation preparatory to the formation of an ovum or a sperm, the paternally derived chromosomes freely Just as the foregoing asexualizes sperm and ovum, the individual they produce, female or male, is neither exclusively female nor exclusively male, but a balance of the two, a phenomenon that is the best tribute to the inseparability of and the cooperation between Yin and Yang. "Sex determination is the result of a genie balance between factors of maleness and femaleness that are present simultaneously in each sex." [11] In genetic terms, in every human being, factors controlling maleness and femaleness are codominant. Each human being is thus a hermaphrodite, the HERMaphrodite being males, and the hermAPHRODITE being females, depending on which way the balance tilts. (No wonder, there are many shades in between, mindwise and/or bodywise). "The realization of the wholeness of human personality always depends on the development and integration of both (feminine and masculine) sides. This discovery is deeply confirmed by the Asian symbol of Tao, the great life swinging between the poles of Yin and Yang." [42] It is interesting to note that testis produces both adrogens and estrogens, and so does the ovary, in differing proportions. Even gross anatomic structures tend to be sex-indifferent: [20] "The arterial blood supply, venous and lymph drainage and the nerve supply of the structures comprising the external genital organs of the female are similar to those relating to the homologous structures in the male." In endocrinologic practice, the terms feminization of a male and the masculinization of a female speak for the inherent balance of two polar forces, in clinical terms. "It is an intimidating thought that there is more information on organic chemical synthesis packed into the head of a spermatozoon than in all the 200 volumes of The Journal of Biological Chemistry." [8] The same could be said of an ovum. Yet, left on its own, a sperm or an ovum be. haves as a biologic dead-end, incapable of doing anything. No cell could be metabolically more inert - "for weeks, months, or even years." [10],[11] Yet these dead cells (sperm can be stored frozendead for a millenium) beget life, once brought together. Could one say they constitute half-life or half-cell? Knowing the universality of Yin-Yang, it would be quite scientific to say that an ovum is Yin, sperm is Yang and we all are the embodiments of Yin-Yang, - the Wattsian Two Hands of God. [44]
A la Einstein, [1] CEM (CytoElectroMagnetism) and Yin-Yang are, as concepts, free creations of mind which have the merit of allowing us cytologically, genetically, and biologically to take out more than we put in. As such the borderline between the animate and the inanimate is hazy; CEM and Yin-Yang erase the line further thus justifying the growing basic assumption that living matter and physical matter are part of the same continuum and subject to the same natural laws. If Einstein abrogated the dichotomy between matter and energy, CEM and Yin-Yang could do a similar job by presenting all of we living as essentially field-effects. The molecules making us provide the matter, the abstract but greater truth between the molecules makes us what we are, for better or worse. Modern genetics and cytology has had a chequered career: We taught that there are 48 chromosomes in a human cell, till Tjio and Levan proved them, in 1956, to be 46. [16] We gave Beadle and Tatum Nobel prize for their one-gene-one-enzyme hypothesis. Soon things changed completely, upsetting this Nobel-winning view. Without ever defining it precisely even for once, we have talked and talked of a gene or the gene, to learn only recently that a gene or the gene is far more complicated. [13] May be, one service that CEM and Yin-Yang may do is to provide some more denouements in our thinking on cytology and genetics. CEM and YinYang claim no more than pointing a finger towards a possibly different way.
[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]
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