The cornerstones of the sense of individuality and uniqueness that pervade the members of the human species are its immune, hormonal and nervous systems. These systems are deeply rooted in the chordate phylum and developed along other lines in other phyla. The sense of individuality and uniqueness culminates in the human species but is not restricted to this species. The members of at least one other hominid species, the chimpanzee, have an ego and recognize themselves in a mirror. Also, most mammals and birds are gregarious and will endure without rebellion various states of social inferiority or even subjection to man. It is extremely rare but not impossible to see a dog, parrot, horse, dolphin and elephant show the “freedom” syndrome that sets a limit to the degree of its subjection and manifest signs of rebellion or disturbance. Yet, manifestations of this type are not unknown among animals endowed with a high degree of consciousness (elephants, parrots, dogs, dolphins) while among humans, blind subjection to sexual and social imperatives are not uncommon.
22.214.171.124 Interferon: integrity of the cell
The maintenance of the integrity of the eukaryotic cell was of primordial importance at the moment of its appearance. The problem was to avoid invasions from more primitive life forms, such as viruses. This was all the more likely because the protozoa acquired the aptitude to swallow up particulate matter and digest it. There was a great danger that they would absorb viruses liable to produce a deadly invasion. How could an invasion be offset?
The formation of proteins proceeds within the cells of prokaryotes and eukaryotes according to the scheme: double-stranded DNA forms single-stranded RNA that serves as a messenger for the synthesis of protein. There should never occur in these cells a synthesis of double-stranded RNA of great length. Yet, double-stranded RNA of considerable length is a common feature of many viruses. DNA in plants, fungi, flies and vertebrates produces sequence-specific double-stranded RNA of a length of about 500 bases, which in turn produces sequence-specific single-stranded RNA’s with a length of 21 to 25 bases, which are able to destroy the messenger RNA synthesized by the original DNA. This method of post-transcriptional gene silencing does not seem to have any relation with the production of interferon.
From the level of bacteria onwards, a mechanism has been devised whereby the occurrence of double-stranded RNA in a cell triggers the production by this cell of a protein called interferon. The role of interferon is to interfere with the synthesis of proteins dictated by the foreign double-stranded RNA. Interferon activates antiviral pathways and directly inhibits viral replication within cells. This mechanism of defense was maintained by the metazoans and is found in plants, arthropods and chordates. Interferon-producing cells (immature dendritic cells) show limited reactivity to bacterial products, consistent with the notion that they are destined to combat viral infection.
126.96.36.199 Immunity: integrity of the multicellular organism
Medawar found in 1953 that adult mice accepted foreign skin grafts if they had been injected as babies with cells from the donors. Based on this observation, Burnet suggested in 1959 that the immune system functions by making a distinction between self and nonself. This paradigm lasted until about 1994, when the number of paradigmatic deviations were such that amending the theory became mandatory. P. Matzinger proposed that the immune system is more concerned with entities that do damage to the organism than with those that are perceived as foreign1.
The problem was the maintenance of the integrity of a multicellular organism. Some unicellular molds similar in their aspect to white blood cells assemble into a slug when the density of the population is high. The slug is the seat of formation of reproductive spores that are disseminated later. The formation of a multicellular organism by these molds is transient and practiced for reproductive purposes only. The number of individual amoebae that aggregate to form the slug is by no means stringently defined. Also, an individual amoeba may fulfill any role in the slug: it may form the stolon, or else a reproductive spore, or else become part of the outer protective membrane (see fig. 3.14).
How could the possibility be avoided that a disruptive foreign cell integrates into the slug? At the lowest evolutive levels of the metazoans arose the problem of the integrity of the organism. Some of these metazoan forms were naked, some were free moving and these forms were vulnerable. How could the possibility be avoided that foreign cells integrate into and perturb the good functioning of an organism made of multiple cells? The rejection of foreign cells by an organism, i.e. cellular immunity resulting in the elimination of intruder cells, was not an achievement immediately acquired by metazoans.
188.8.131.52.1 Sponges: species recognition. The individuality of the sponges extends only to the species. Whereas one or several porifera sponges ground up into individual cells reassemble into a functional sponge again, the cells of different species do not join to form a colony. Persistent aggregation into a functional sponge is species-specific and attributable to a large glycoprotein molecule present at the surface of the cells. Cells from the same species are accepted but intruder cells from other species are not accepted, although they are not killed. At this level of organization, the imperialism of the individual organism is non-existent. Acquired immunity under the form of cell killing as a result of incompatible cell reactions is absent.
184.108.40.206.2 Coelanterates: strain recognition. Recognition of foreign cells leading to their death is a characteristic of coelenterates. Grafts practiced between two different species result in cell death within a week. Clones derived asexually from a primordial single colony fuse together when grown in contact but unrelated colonies of the same species fail to fuse. The incompatibility results in overgrowth in one or both colonies of any two fused strains of the same species.
220.127.116.11.3 Echinoderms and Protostomes: immunological memory. The mesenterian hypothesis postulates the evolvement of echinoderms (starfishes, urchins) from a coelenterate medusoid form. Echinoderms are neither protostomes nor deuterostomes. They descend in a direct way from coelenterates and Vandebroeck classified them as “cycloneurians”‘. However, nucleic acid analysis classifies them as primitive deuterostomes. Primordial cell-mediated immunity exists in echinoderms. The body of echinoderms possesses white cells that reject and kill cells originating from a foreign species. In contrast, inoculated cells taken from an organism of the same species survive 130 to 185 days without rejection. The existence of a short-term immunological memory in echinoderms is, however, apparent by the fact that repeat cell grafts from the same donors are rejected within 60 days instead of 185.
In protostomes (worms, mollusks, arthropods), cellular immunity is difficult to ascertain because most animals belonging to these phyla have short lives. There has never been found in these animals a humoral immunity patterned on the vertebrate antibodies. These antibodies are highly specific and susceptible to a drastic increase upon repeated inoculation of an antigen. Sharply specific reactivities of this type have not been induced in protostomes. Transplantation immunity with concomitant immunologic memory has been demonstrated in annelid worms.
The battle between infectious microbes and their hosts is very ancient and the frontline defense adopted by insects and mammals are similar. In mammals, the innate immune system defines a rapid first response to infection that activates directly host defenses, and also stimulates the specific immune responses. Insects share features of the mammalian innate immune response.
18.104.22.168.4 Protochordates: absence of a humoral response. The protochordates that immediately precede vertebrates in phylogeny are provided with a cell-mediated immunity. This immunity has the characteristics displayed by the coelenterates. Colonies of tunicates put in contact through their stolons, react by overgrowth and local necrosis. A humoral antibody response, i.e. vertebrate-type circulating antibodies, could not be demonstrated. Immunological memory is shown to be present in protochordates by the fact that repeated inoculation of foreign cells is answered by encapsulation of these cells and ejection. This reaction to repeated stimulation is slightly reminiscent of a vertebrate-type secondary responsiveness.
22.214.171.124.5 Vertebrates: humoral and cellular immunity. The highest level of immuno-evolution is found among vertebrates, where cell-mediated immunity and humoral immunity are integrated. The immune system uses more that 200 genes to mark the body’s own cells and identify invading pathogens. This block of genes is known as the major histocompatibility complex (MHC). In vertebrates, the immuno-surveillance against foreign cells is made by a population of lymphocytes produced in -or dependent on- the thymus or a homologous organ. The surface of all the cells of an adult vertebrate is covered by what one may truly call signals of molecular identity. These are the histocompatibility antigens. These molecules play an essential role in the maintenance of the integrity of the organism and are implicated in all the mechanisms that promote the rejection of organ grafts. This cell-mediated immunity is complemented by a humoral immunity from the level of the agnates onwards. The humoral immunity is under the command of lymphocytes produced in bone marrow or homologous organs. In the course of evolution, the diversity of antibodies attains progressively greater degrees of complexity.
The imperialism of the individual is thus much greater in the chordate phylum than among protostomes. Vertebrates, and especially mammals, are composed of species wherein each single individual is usually violently reactive upon the intrusion within its body of any foreign cell. Only cells from a biological twin are accepted without rejection.
126.96.36.199.6 Placentary mammals: fetus tolerance. In placentary mammals, the problem of protection of the organism is compounded by the fact that there is a long permanence of the fetus within the maternal body. By all accounts, the fetus is a foreign body that ought to be rejected. A developing embryo is at mercy of the natural and specific immune systems of the mother. A system of acceptance of this foreign body in the womb of the mother was elaborated whereby the mother will not reject the fetus and vice-versa. The newly formed organism delays the discrimination of self and non-self until after birth. The elaboration of such a system of intra-uterine embryonic growth was essential to reach the Primate level of evolution, because it allowed an unrestricted arboreal life. Indeed, such a life presupposes a good development of the central nervous system and, in mammals, infants while still in their mother’s womb could reach this development. Once born, the babies were developed well enough to steadfastly cling to their mother’s fur. The precociously born marsupials are unable to do so and the sole marsupial species that achieved a degree of success in an arboreal life is the opossum.
The uniqueness of each human being is not restricted to protein composition but can be found in fingerprints, earlobe patterns, and even graphological characteristics. In this case, it is significant that the particular writing is maintained when one writes with the tip of one’s fingers on a small piece of paper, and also when the whole body is involved in the writing of huge letters: the graphological characters of the writer remain in both cases clearly distinguishable.
6.1.2 The hormonal system
The perception of the internal and external worlds through a nervous system ending in various sensory organs was backed by hormones which themselves relied for their action on the simple biological material devised by more primitive organisms, such as prostaglandins, cyclic AMP and cyclic GMP. Hormones are recognized by receptors located on the surface of the target cells. The binding of the hormone increases the production of cyclic AMP, which in turn instructs the cell to respond in a characteristic way. Prostaglandins either increase or decrease the cellular concentration of cyclic AMP and modify the cyclic AMP control of RNA synthesis. In the brain, the prostaglandins influence and affect neuronal activity by regulating the release of neuro-transmitters such as norepinephrine and acetylcholine (Fig. 6.1), also through an action on cyclic AMP.
Other hormones, such as the steroids that play such a great role in sexual differentiation, enter freely into cells. They bind to portions of the genetic material and in this way trigger the preferential synthesis of the proteins that are involved in sexual manifestations.
Figure 6.1. The increasing complexity of organisms appearing in the course of evolution was accompanied by the use of neuro-transmitters of greater and greater complexity. The simplest and also most ancient neuro-transmitter is acetylcholine. The most complex is serotonin. Some of these neurotransmitters are also hormones.
The availability of at the most 50,000 proteins specified by the genetic material of unicellular eukaryotic cells 2 promoted the utilization of metabolic by-products as chemical transmitters. At a particular time in the evolution of a phylum, a decision is firmly made to make use of such a by-product. Examples of these are insulin, thyroxin, adrenaline, noradrenaline, progesterone, etc. which, once incorporated into the physiological organization of an animal group, can remain entirely untouched in their molecular structure by evolutionary change. Since chemical products devised by eukaryotes are not available in unlimited molecular forms, a hormone usually serves many different purposes.
The exploitation of thyroxin by the vertebrates is an example of this. Thyroxin is found in coelenterates and tri-iodo-thyroxin is found in worms. These substances are also present in protochordates. These thyroid hormones were selected by the chordates to promote the passage of aquatic to terrestrial life. The effect of these hormones on a batrachian’s tadpole during metamorphosis into an adult frog is perceived on respiration, on changes in the hemoglobin type, on induction of albumin synthesis, on increases of turnover of ribonucleic acid (RNA) in the liver, on changes in the eye pigment and on the growth of limb buds.
The multiplicity of action of hormones is accomplished by a reliance on the spatial configurations a chemical substance can adopt and by the existence of refined receptors of the hormone located at the surface of cells of target organs. The diversity of action of many hormones influencing many organs is due to subtle adaptations of the hormonal receptors to different molecular configurations of the hormone.
Histamine, for example, is a hormone that increases the secretion of mucus. Besides this, it also increases the amount of cerebrospinal fluid, increases the permeability of blood vessels, decreases blood pressure, increases the contractions of the muscles of the uterus. It also increases the heartbeats and the flow of acid in the stomach. It seems that most effects are due to the hormone under its form H-1. Acid production and heart beat increase are due to the hormone under its H-2 form (fig. 6.2).
Figure 6.2. Histamine is present under at least two molecular structures, each of which being effective on selected cells of particular organs. There is a possibility that some effects of the hormone are mediated by an unknown H3-form.
Hormones rapidly served as neurotransmitters.
188.8.131.52.1 Acetylcholine. Besides ATP, the phylogenetically most ancient neurotransmitter is derived from ethanolamine. Acetylcholine has a very simple chemical structure. It does not need oxygen for its synthesis and is found throughout the plant and animal kingdoms, starting with the protozoa. In the brain, acetylcholine is a transmitter of information from one neural cell to the next. In the body, it is present in the terminal innervations of muscles.
184.108.40.206.2 Catecholamines. The development of various organs by protostomes and deuterostomes prompted the utilization of a second class of neurotransmitters derived from the amino acid tyrosine. These are the catecholamines whose synthesis requires oxygen. This indicates that they evolved after the appearance of blue-green algae. The first of the series is dopamine. It is mainly through dopamine that the neural network is established. Outside the brain, dopamine induces cardiac stimulation. At high doses it is a vaso-constrictor. At low doses it produces vaso-dilation. The subsequent degradation product of tyrosine that found an application is nor-adrenaline (nor-epinephrine). This neurotransmitter is found in large amounts in the brain of bony fishes and mammals. It is also found at the end-point innervations of viscera. It takes part in the regulation of food intake and temperature. The next useful metabolite is adrenaline. In amphibians, it is the main neurotransmitter in the brain.
220.127.116.11.3 Serotonin. A third neurotransmitter type is derived from tryptophane. Serotonin (5 – hydroxy-tryptamine) is chemically more complex than the other mediators. It is concentrated mainly in the gray matter of the brain and plays a role in the sleeping mechanism, stress and aggressiveness. Ecstasy (3,4-methylenedioxymethamphetamine) heightens sensations, gives a euphoric rush and increases feelings of warmth and empathy by causing neurons to release huge quantities of serotonin and dopamine. In the aftermath, the heavy user, drained of serotonin, is depressed and unable to concentrate. A reduction in the systems that produce serotonin and, more markedly, dopamine, are noticed among ecstasy users, resulting in permanent brain damage (memory loss) and potential vulnerability to Parkinson’s disease.
Neurotransmitters are also hormones. One suspects that dopamine is synthesized in the kidneys and regulates urinary flow. Adrenaline is mainly synthesized in the adrenal-medulla glands. Released into the blood stream, it has an effect on such disparate organs as the papillae, sphincters, heart, blood vessels, uterus, bronchia, and digestive tract. Its presence is correlated with increased tension and expectancy.
6.1.3 Integration of signals by the vertebrates
The chemical (hormones and neurotransmitters) and electrical (nerves) systems of internal signals have been consolidated in the phylum of the chordates.
18.104.22.168 Hormones and nervous system
In evolved members of the chordate group, hormones play a role in the formation of the nervous system. This is peculiar to the vertebrates. In primitive representatives of the phylum of the chordates, such as Amphioxus and Ascidia, the embryonic cells destined to the formation of neural tissue are largely predetermined. Ablation of these cells will deprive the developing embryo of a nervous system. This is the case also for all protostomes, even the most evolved such as insects. The embryonic tissues of insects destined to become nervous tissues are rigidly predetermined. If the embryonic cells supposed to become neural are excised through surgery, the insect embryo will develop further without the formation of nerves. This is no longer the case in evolved forms of the chordate group such as fishes, reptiles and mammals. In their case, the predetermination is gone and any ectoblastic cell, i.e. any of the cells that contribute to the seaming up of the slitted mouth of our primitive anemone (see fig. 5.3 and 5.4), and in general any cell making up the external envelope of the anemone, will develop into a neural cell, if given the proper hormonal stimulus.
In superior mammals, including Man, the interrelation of hormones and nervous system is such that, in the limbic system, also called the archaic cortex mainly responsible for automatic, instinctive and emotion-laden responses, sexual steroids act as neurotransmitters. One of the targets of the hormones is the hypothalamus. The labeling of the brain as being “male” or “female” occurs during fetal life. In females, the brain develops without an additional sexual stimulus because fetal female gonads are inactive. In females, the failure of the hypothalamus to have been influenced by the female hormone oestradiol during the fetal stage induces a feminine behavior that no amount of male hormones administered later will be able to durably change. During the fetal stage, male gonads secrete testosterone, which is transformed, paradoxically, in oestradiol. This hormone acts on the fetal hypothalamus that generates a typically male behavior that no amount of female hormones administered later in life will be able to modify during a durable time. It is now well established that the hormone estrogen affects cognitive functions. Estrogen both enhances and impairs memory.
22.214.171.124 Hormonal individualization tendencies
The genes of the most evolved protostomes, i.e. social insects, determine the fundamental characters of the males and females; the secondary sexual characters of insects are under the immediate control of the genetic material. This is not to say that hormones are inoperant among insects but well that these hormones are not agents of individualization.
In evolved vertebrates, the determination of sex is also under the control of the genetic material. The sex of mammals is determined by chromosomes. However, contrary to insects, various sexual attributes are differently expressed in each individual mammal according to hormonal production. The expression of the innumerable secondary sexual characteristics is left to the care of hormones, which control one another through feedback mechanisms. And this is why height, musculature, size of breasts, pilosity, libido, aggressiveness, etc. vary in the evolved vertebrates from individual to individual. Female sexual organs strongly influence the external secondary characteristics of the female, making every single female different from all the others. The same is true for male sex hormones predominantly produced by males. The differences are visible. These characteristics strongly influence the behavior and lust of males and females and individualize their copulation tendencies. This individualization is brought to a summit in primates.
At the end of the 19th century, sex was seen as the center of life, vitality and energy. The eminent French physiologist Charles Brown-Séquard injected himself in 1889 with testicular extracts of dogs to “rejuvenate” himself. He died 5 years later and covered therewith himself and science with ridicule. It was then believed that male and female sexes were in direct opposition to one another, and the concept of sexual antagonism developed. The idea that male and female are binary opposites resonated with cultural norms of doom and decadence that followed the Napoleonic destructions, the French Commune and the rise of the first Germanic Empire, in 1871. Decadence and Satanism were well represented by the painter G. Moreau. To Rops, as to Toulouse-Lautrec, Baudelaire, Byron,Verlaine, Huysmans, Rimbaud and James, the Devil is, above anything else, the master of sex. Woman is dominating, decadent, perverse, possessed by Satan, living in paroxysms, in a world that is doomed (fig. 6.3).
Figure 6.3. F. Rops. The temptation of St Antony. 1878, Cabinet des estampes, Bibliothèque royale Albert Ier, Bruxelles. This painting summarizes the spirit of the times: Christ and Satan join forces to expose to Antony : ‘I want to show you, my good Antony, that you are crazy in adoring your abstractions….If the Gods are gone, Woman remains to you and, with her love, the fecund love of Life’. F. Rops (1833-1898) was a talented artist, endowed with a vivid critical spirit but too obsessed with pleasures and women to achieve excellence in painting.
The model of functionally opposed sex glands was found oversimplified after the discovery by Zondek in 1934 of estrogen in the urine of a stallion: androgens and estrogens were found in both women and men. With primates and man, the predominant hormone of each sex no longer mediates sexual receptivity, as opposed to sexual attraction. This fact explains many seemingly abnormal behaviors. Both sexes produce not only their determinant hormones but also hormones of the other sex. The sexual drive of the females i.e. the libido, is mediated through a male sex hormone (androstenedione). The female sex hormones of the female thus increase the attractiveness of the female and stimulate the male while the male sex hormones of the female maintain and amplify her responsiveness to the male’s advances. When these masculine hormones are sufficiently influential, it is she who initiates the coitus. Such a hormonal modulation of the behavior of various members of a species is an extraordinary departure from the commonly found genetic determinations.
2. In humans, about 30,000 genes produce about 100,000 messenger RNAs, which in turn synthesize about 100,000 proteins. These proteins, in turn, may be selectively modified and even shortened by proteases, giving them new properties.