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Home , Mental chronometry, Time perception

1st International Conference on Advancements of Medicine and Health Care through Technology, MediTech2007, 27-29th September, 2007, Cluj-Napoca, ROMANIA

Timing Life Processes

Dana Baran

Abstract — Natural such as planet movements and biological timekeeping gears inspired artificial timers including water clocks, sandglasses, mechanical, electric and finally electronic systems. Contemporary medicine and biology reconsiders temporal morphogenetic and functional patterns interpreting life processes as highly sophisticated clockworks, liable to mathematical modelling and quantification. and chronomedicine opened a vast theoretical and applicative field of interest. Keywords: chronobiology, temporal monitoring devices, biological , mathematical modelling.

1. INTRODUCTION exogenous synchronizers periodically adjust to the cosmic . [2] At the very beginning, breathing and heart rate, Throughout the the perspective on biological pulse frequency, menstrual cycles and vital forces were phenomena temporal dimension, i.e. on their dynamic perceived as led by rhythmic vibrations of the stars, the sun structure and function, followed several synchronic and and the moon. Nature exhibited both clocks and ! diachronic patterns, possibly defined as astromy Now living beings are usually forced to disrupt their innate thological, cosmobiological, mechanistic, physico- biorhythms and adapt to man-made temporal cues imposed chemical, statistico-mathematical, physiological, psy by shift work, jet travel, abundance of vegetables and chological or philosophical insights. [1] After 1950, products, irrespective of time of or , in scientists started to elaborate a coherently integrated vitro fertilization, cloning and genetic manipulation which multidisciplinary and even transdisciplinary approach to equally play with biological time and social destinies. biological rhythms. Largely known as chronobiology, it lately generated a medical subdivision: chronomedicine. 3. ASTROMYTHOLOGY [2, 3] Cyclic behavior estimation of living things tightly relies now on modern theories, technical progress and Primeval medicine interpreted life course in terms of accurate data processing: so chronomedicine is no astrology and astronomy, intermingled with mythological exception from evidence-based disciplines! symbols. The sun, the moon and other planets were gods and goddesses, turning around in interdependent rings, 2. ENVIRONMENTAL CLOCKWORKS causing and predicting differentiated bioreactivity, 2.1. The Cosmic Clock Paradigm robustness and illness, birth and death, flourishing and degeneration. Rhythms began to correlate with numbers The whole universe resembles a clock-like device, imagined – and ratios, as in ancient Egypt, Mesopotamia, Greece, but as Voltaire put it in the XVIII-th - by a genial in pre-Columbian Mexico, too. [5, 6] By their lives, clockmaker god. The star clocks, the , the moon, the divinities regularly controlled recurrent cosmic processes. planets, the plants and observe interfering quasi- constant periods and mark their completion by specific events. 4. COSMOBIOLOGY Such phenomena undoubtedly led to the invention of imitative time-machines with wheels, teeth and striking trains, evolving Biological reality was plotted against a cosmic from the shadow pole stuck in the ground, to the background. Its evolution or timed becoming, referred to as telling the with one error in 3000 . Maybe vital dynamics, manifested in keeping with both surprisingly, today, chronobiologists still debate on day-night cycles and seasonal rhythms. Ancient China chronoastrobiology, a chronobiological branch dealing with considered that interchangeable yin-yang energetic balance chronomics, i.e. time structures, in its relation to cosmos and periodically oscillated according to macrocosmic- biosphere. [4] Meteoropathology is included, along with the microcosmic interpenetration rules. [5, 6] Consequently, recurrent health impact of geo- or/and helio- magnetic field pulse frequency based diagnosis and prognosis of disturbances, in a more encompassing and traditional view. disease expressed a complex philosophy of cosmoenergetic medicine and so did the twelve meridians crossing the 2.2. Living Beings as Adaptive Biological Clocks body and bearing 365 acupunctural points along them. Even when anthropomorphic deities were lacking, golden Living creatures, – chronogenetically determined numbers, proportions and ratios played key-roles. biological clocks, - represent time-keeping self-controlled or anti-entropic feed-back looped entities, which 5. NUMBERS GOVERN THE WORLD

For Pythagoras and Plato, arithmetic, geometry and music Dana Baran is with the Faculty of Medical Bioengineering, ”Gr. T. Popa” University of Medicine and Pharmacy, Iaşi, belonged together, the supreme divinity was the number Romania, phone: +40-232-213-573; fax: +40-232-213-573; e-mail: itself able to “rule over the Universe”. Health derived from [email protected] ideal mathematical laws, governing the incessant fight

465 1st International Conference on Advancements of Medicine and Health Care through Technology, MediTech2007, 27-29th September, 2007, Cluj-Napoca, ROMANIA opposing good and evil. [5, 6] According to Philolaos of Giovanni da Dondi (1318-1389), professor of astronomy, Crotona (V-th century BC), health resulted from the logic and medicine at Padua and of medicine at Florence cosmic harmony he called “eurhythmics”. Hippocrates Universities, technically featured an himself, in the same golden of the V-th century BC, containing an escapement composed of a band-saw crown believed in the significance of critical days for anticipating wheel and a verge. [8] By and by, scientists detached the disease course and applying more efficient timed from the occult magical background of the Renaissance, therapies. He also recognised chronopathological aspects: humanists turned to encyclopedists, and mechanistic diurnal or nocturnal incidence of acute episodes, seasonal philosophers substituted both wizards and alchemists.[9] occurrence of certain diseases. Galen (II-nd century AD) instead had often recourse to astrological medicine. [5, 6] 7.2. The Turning Point Geto-Dacians equally set up a solar as illustrated by their circular temples, indicating propitious and The magical mechanistic genius of the Renaissance unpropitious moments. [1, 6] No wonder Zalmoxis was anticipated robotics, prepared bionics and seeded the germs considered Pythagoras` apprentice and Dacian priests the of prosthetics, performing public miracles and beneficiaries of ancient Egyptian wisdom. [6] thaumaturgical exploits. [1]This marked the turning point of iatrophysics and iatromechanics, whereas iatrochemistry 6. MEDIEVAL TIMING PATTERNS redimensionated alchemy, phytotherapy, mineralogy and 6.1. Christian Salvation Time animal organ extracts for more efficient therapeutic blends, often administered according to “chrono-optimized” In medieval Europe, learning mainly emanated from treatment schedules. Nevertheless, as yet, physicians did religious institutions which were particularly concerned not abandon their zodiac books since astrological medicine with strict timekeeping. Saint Augustin, Dionysius maintained its high profile. Paracelsus (1493-1541), the Exiguus, - a Danubian Scythian by birth-, venerable Beda symbol of iatrochemistry, was such an emblematic or Alcuin were among the early most famous personality. Besides, he kept on being a successful contributors. [7] Not only were new calendars conceived, alchemist. [5, 6, 9] Throughout the XVI-th century, but canonical , prayers, lauds and vespers ordered mechanical clocks became quite common and in the XVII- monastic life that directly conveyed sacred rhythms to th century the pendulum was invented. Subsequently, a profane destinies, - “in season and out of season”, more adequate quantification of time-related bioreactivity reflecting and emphasizing God`s messages. The church and interrelationships with the surrounding Universe was clock struck the cosmic hour on Earth. Real and false enabled. Heart rate and wrist pulse constituted reference clocks were , for instance in Malta, in every place, oscillators Galilei (1564-1642) used to consult in Pisa aimed at getting rid of devil`s sinister impact upon cathedral for evaluating the candelabrum-pendulum . Christ and the Holy Virgin metaphorically periodic oscillations. Santorio (1561-1636), professor of personified the sun and the moon, respectively. physiology at Padua, measured the radial pulse with his famous “pulsilogium”, -a pendulum-based instrument-, 6.2. Islamic Middle-Ages that preceded the sphygmometer. [5, 6] The pulsilogium could adapt to heart rate movements by the adjustment of Arabs and Persians valorised and further amplified its strings. The same was true with Lodovico Zacconi Greek, Roman and Byzantine knowledge, making time (1533-1627), an Augustinian friar and musician in Venice pieces and astrolabes on solid astronomical ground. The and Munich, who controlled the tempo of his concerts by astrolabe dial consisted of a movable sky map rotated to the cadence of his gate (“andante” in Italian language show where stars were at every time of day and . [7] means “walking’) he believed to be induced by the heart The time of prayers was capital and religiously observed. rate: “the heart, he ascertains, reveals what is rapid and God could influence the of facts and what is slow by its own movement”. [10, 11] Deafness determine health and welfare to prevail over suffering must have made Beethoven feel the same.[11] So, initially, and pain. Historians state that, from China and India, it was the heart to indicate “the clock mean time (CMT)”! mechanical ideas reached the Islamic world and then spread to Europe in the XIII-th and XIV-th centuries. 7.3. Enlightened Clockworks

Enlightenment forged new interdisciplinary research 7. CHRONOS EX MACHINA 7.1. The Renaissance Mechanistic Magic domains from a rational, yet mechanistic perspective, leaning over the machine-man concept. [12] Iatrophysics, It was only by the middle of the XIII-th century that iatromechanics and iatrochemistry intensely applied physical preliminary mechanical clockworks appeared. The and mechanical principles to vital processes modeling and mercury clock already included the essential components measurement, conceiving humans as animated machines, of a mechanical clock. In 1271, Robert the Englishman whereas, paradoxically, iatromathematics continued to described in his astronomy book such an instrument correspond to medical astrology. [5, 6] Now, it was the endowed with a flywheel - “a disc of uniform weight in clock, a more and more precise and often portable device, to every part”. [8] Dante mentions in his “Divina count the heart beats by its regular oscillations, telling its Commedia-Il Paradiso”-, written between years 1317- own CMT: “the cardiac mean time”. 1320, a clock, probably symbolizing temporal order in (1629-1695) achieved a in 1657 and in the Heavens. It is interesting to note that, in 1364, 1670 built a spiral spring balancer for more accurate

466 1st International Conference on Advancements of Medicine and Health Care through Technology, MediTech2007, 27-29th September, 2007, Cluj-Napoca, ROMANIA measurement of oscillatory periods. The Dutch physicist Dame (1503-1566), a physician astrologer, Girolamo improved isochronal pendula he described in "Horologium Cardano (1501-1576), a mathematician and a physician who Oscillatorium" in 1673. [7, 8] With Huygens, a scientific also illustrated medical astrology, Nicholas Copernicus revolution took place and time estimation left the archaic (1473-1543) a notorious physician astronomer, Athanasius once and for ever. In the XVIII-th century, highly Kircher (1601-1680), another “polymath” monk, familiar precise clocks had only a two second error a . [8]. with mathematics, physics, magnetism, astronomy and Doctor John Floyer (1699-1734) stands for the first medicine, who equally fancied a pulse , whereas Pierre physician to have examined the pulse a watch in his hand Charles Louis (1781-1872) engaged himself both as a (1707-1710): this was the pulse watch endowed with a physician and a pioneer biostatistician. [5, 6, 14] hand. Only later the second hand was added to mechanical clocks. In 1752, again, pulse frequency in the 8. THE PINEAL EYE afternoon represented an ideal metronome for flute players, wrote in his Essay on music and performance Joachim Following the theories of Plato, Aristotle and Galen, Quantz (1697-1773), a renowned flutist himself, composer, Descartes (1596-1650) elaborated his own conception flute maker and teacher at the Prussian court. [10, 11] about the pineal gland, considered the seat of soul, Musical harmony expressed and restored health. In 1761, imagination, reflected spirits and common , from a John Harrison suggested a working by metaphysiological perspective on sensations, the winding and unwinding of a spring. If Santorio is held to and nervous reflexes. [15] This «third eye», also holding have put the first numerical scale for clinical use on Galilei's a paramount role in Indian philosophy, is officially thermoscope, Fahrenheit (1686-1736), Celsius (1701-1744) accepted today as a key endogenous synchronizer of and Réaumur (1682-1757) and Sir Thomas Clifford Allbutt biorhythms by its regular nocturnal melatonin release. [2] (1836-1925) set up newer, more precise and smaller thermometers. Basch and Zadek (1881) and Riva-Rocci 9. HOMEOSTASIS AND BIORHYTHMS (1896) achieved pletismographs. [10] From the XVIII-th and XIX-th centuries on time related variations of biological With Claude Bernard`s (1813-1878) definition of the functions and structures in health and disease could be internal milieu constancy (1865), that later on Cannon assessed. Circadian rhythms were documented by Elsner (1871-1945) called homeostasis (1929), almost uniform (1778), Zimmerman (1793), Reil (1796), Falconer (1797), adaptive variations of biological morpho-functional Hufeland (1797), Autenrieth (1891), Wilhelm (1806), characteristics were envisaged. [16] After about one hundred Barthez (1806), Knox (1815), Testa (1815), Zadek (1881), years, chronobiologists would, however, amend this Howell (1898), Jellender S(1900), Weiss (1900), Hensen statement in that both basic and adaptive bio-oscillations fit (1900). [10, 13] At Paris University, J.J. Virey (1775-1846), to a biorhythmic pattern, reaching time-related maximal a French pharmacist, naturalist and physician, wrote the first (acrophases) and minimal (bathyphases) amplitudes. A known doctoral thesis focused on biological rhythms. biorhythmic homeostasis had to be admitted in the XX-th Furthermore, he introduced the decimal system to laboratory century, complementary to the “oscillatory life” formulated and anthropometry. Virey envisioned that innate biological by Claude Bernard with reference to rigorous, repetitive, rhythms of living clocks were entrained by periodic harmonic, ordered constant vital phenomena. [2, 17, 18] environmental changes, such as the day-night repetitive alternation. He reported that the effects of drugs varied 10. TECHNOLOGY BASED CHRONOMEDICINE according to their administration time. He collected and published quantified time series, demonstrating human In the XX-th century, quantum physics and informatics circadian and annual mortality rhythms. Statistical analysis approaches to biology stemmed out. Theoretical advances of Virey's data using modern time series methods confirmed paralleled technical progress. To biopotential recordings and his deduction that human mortality exhibits rhythmicity.[14] chronograms, new methods were added. X-rays, radio Due to technical progress, -wake and rest-activity isotopes, positron emission tomography, ultrasounds, radio cycles, respiratory and heart frequency, arterial blood immunology, autohistoradiography, immunohistochemistry, pressure oscillations, body temperature and weight variation electron microscopy, genetic engineering, mathematical along with other biochemical, biophysical, morphological modeling and computer assistance became part of everyday and functional variables could be more accurately evaluated, biomedical investigational protocol able to define living quantitatively and qualitatively assessed in a time-dependent beings different “chronomes”, i.e time structure. [2, 3, 4] manner. [2] Consequently, clinically and experimentally Sophisticated on-line and off-line (tele)monitoring devices documented biorhythms were ascertained. Pulsilogia, appeared meant to better seize the temporal peculiarities of sphygmometers, manometers, thermometers, pletismographs biological variables course. (Figure 1) completed patients' physical examination. [1, 5, 6, 10, 13]

7.4. Doctors: Physicians and Physicists

A remarkable fact emerged from this historical retrospective. Physicians were most of their own engineers or physicists. The already mentioned da Dondi was among them, along with Jean Fernel (1497-1558), mathematician, astronomer and eventually a physician, Michel de Nostre- Figure 1. Actiwatch actigraph: two day activity record

467 1st International Conference on Advancements of Medicine and Health Care through Technology, MediTech2007, 27-29th September, 2007, Cluj-Napoca, ROMANIA

Subsequently, chronomics emerged, complementing 12. CELL CLOCK MODELS other “omics”: proteomics, genomics, transcriptomics, 12.1. The Cellular Oscillator: An Attractor physiomics, metabolomics. Owing to efficient up-to- cell biology concepts and bioengineering methods, Biologically, many cellular clock models – comparable to chronogenetics proved the existence of cellular clock automata” - have been suggested, but they mainly are genes, pacer and/or calendar cells, identified molecular transcriptional ones and correspond to temporal frames of ontogenetic programs, described immediate early genes reference. [2] Mathematically, cellular clocks are frequently and late genes with specific roles in timing cell signaling modelled as either simple or strange attractors. (Figure 2) cascades, in achieving a properly timed noise to signal ratio, from “womb to tomb”. [2, 19, 20] Modern biomathematical models developed reflecting normal and pathological conditions, biodiversity as a whole, and the subtle properties of non-linear, dissipative, fuzzy living systems. [21] Statistics adapted to the temporal logic of life. Boltzmann machines learning algorithm testifies it.

11. THE GAME OF LIFE

Facts that dominated the dawn of the modern included Einstein`s (1879-2001) theories of relativity (1905, 1916). [21, 22] scientifically proved its «metamorphic» character and clocks just failed to Figure 2. Evolution of a simple attractor (lef) to a chaotic measure it since not designed to do so. Clocks principle attractor (right) (after Heudin, 1998) [28] had already been integrated to thinking machines in the Renaissance period, like Wilhelm Schickard's (1592- A controlled chaotic attractor could provide multifrequency 1635) calculating clock (1623) which included a set of outputs that determine rhythmic behaviour on different time Napier's bones, and the mechanical calculator – the scales (e.g. ultradian and circadian) with the facility for rapid Pascaline-, devised in 1642 by Blaise Pascal (1623- state changes from one periodicity to another. [27, 28, 29] 1662). [23, 24] In the XVII-th century, Gottfried Wilhelm Periodic attractors’ transition to chaos may equally occur. Leibnitz (1646-1716) constructed another calculator, - the [18, 27, 28, 29] In chronobiology, too, chaos theory and stepped reckoner-, employing the stepped gear principle fractal geometry coexist and complement each other in and in the XIX-th century, Charles Xavier Thomas de rendering the complexity of non-linear dissipative yet Colmar (1785-1870) made a more successful calculator, cycling living systems. Information entropy partly explains the Arithmometer (1820), working on the same stepped the thermodynamic hierarchical behaviour of the cell clock gear principle. Even most of today`s computers, based on ultrastructural “wheels”, and Boltzmann`s mechanical von Neumann architecture, possess a clock component, statistics could probably help predict their “choices”, too. establishing the rate at which data are transferred in the working cycle. [24] Computers enormously enlarged 12.2. A Neurokinetic Clock: The Interval Clock cooperation between mathematics, informatics, and biology as a whole. Norbert Wiener (1894-1964), but to Apart the master mammalian clock illustrated by the some extent also Stefan Odobleja (1902-1978) hypothalamic , tightly connected contributed to the appearance of neurocybernetics, the to the and the pineal gland, an interval and a of control and communication in the nervous miliseconds timer were identified. The mood controlled system. [25] Much indebted to (1916- interval timing of the brain suggested by Buhusi and Meck 2001), played a fundamental part in (2005) derived from artificial and neural this respect. Cybernetics enabled robotics, artificial network paradigms. It was supposed to explain high intelligence and automation progress, in parallel to frequency neuronal firing rates (second to minute range) of artificial neural networks, well-known non-linear ultradian (τ<20 hours) biorhythms. [30] The interval statistical data modeling tools. This field originated at the shares many properties with the pacemaker– crossroads of mathematics, statistics, computer science, accumulator timing models and would act by coincidence physics, neurobiology and electrical engineering. Digital detection at corticostriatal and striatal levels. Interval electronics soon emerged. With pencil and graph paper timing is central to broader coordination of tasks such as alone, Von Neumann had also created the first self- walking, manipulating objects, carrying on a conversation replicating cellular automata taking advantage of their and tracking objects in the environment, to understanding exponential growth, and in his book “Theory of Self temporal order of events. timing acts at Reproducing Automata” he had fleshed out the concept cerebellar level and probably originates in the intrinsic of a universal constructor. [24] Devised in 1970 by the properties of the neurons. It ensures , speech British mathematician John Conway (1937- ), the game generation and recognition, playing music and dancing. of life theory used cellular automata to create generations Both emotional states and impinge upon brain`s in keeping with symmetry-dissymmetry, order-disorder, internal clock, resulting in a highly differentiated harmony-chaos, transition or fluctuation states. [26] subjective of both real and virtual time.

468 1st International Conference on Advancements of Medicine and Health Care through Technology, MediTech2007, 27-29th September, 2007, Cluj-Napoca, ROMANIA

13. RHYTHMOMETRIC STATISTICS 14. PSYCHOLOGICAL, HISTORICAL AND SOCIAL RHYTHMS Biorhythm quantification and mathematical expression 14.1. Cognitive and bioinstrumentation relied on the advancement of statistics itself. John Graunt (1620-1674), Christiaan Huygens (1629-1695) and With Franciscus Cornelis Donder (1818-1889), mental Edmond Halley (1656-1742) established statistical analysis became a tool in , inspired principles in the XVII-th century and limitedly applied neuroinstrumentation, preceded neurocybernetics. Today, them to medicine. [5, 6] Even though Cl. Bernard claimed brain activation temporal characteristics are investigated that the “average man” of statistics rather hides than by functional imaging techniques: biopotential recording, reveals the truth, doctor Pierre Charles Alexandre Louis positron electron tomography, magnetic resonance. [35, (1787-1872), his contemporary, implemented statistical 36] The challenging subjective chronoperception and biomathematics, - i.e. “the numerical method”– and individual temporal manifestation still raise psychological probability calculation, to the estimation of disease uncertainties and philosophical questions which in turn incidence and/or prevalence, prognosis and therapeutic incessantly stir up scientific imagination and creativity. outcome. [5, 6, 13, 16] Experimental, clinical or laboratory findings could from now on not only be monitored and 14.2. Time in modern Romanian Philosophy recorded, but statistically interpreted, too. Biostatistics and biomathematics were born. Inseparable from In modern Romanian philosophy, Vasile Conta (1845- chronobiology, rhythmometric statistics or biorhythmo 1859) had the intuition of general oscillating processes, as metry stemmed out and adapted to time-related data he shaped his “universal undulation” theory. If for Conta processing. [2] Originally limitedly applied to life resembled a non-ending winding evolutionary spiral, psychosomatic events, as did mathematical chaos and for Herbert Spencer (1820-1903) rhythmic behaviour of fractal dynamics, rhythmometric analysis soon extended to living and non-living things was transient but ensured examining psychological, social, historical and their birth, splendour and decay. [37] Vasile Parvan astrobiological rhythmic phenomena. [29, 31, 32] (1882-1927) distinguished a “spiritual rhythm” intimately Chronograms together with polar plots and attractors were synchronized to cosmic cyclic vibrations, “historical drawn. For the time being, equations of the estimative rhythms” originated from. [38] Reiterating Bousquet`s curve, MESOR, cosinor, and ANOVA methods represent assertion (1923), Fernand Braudel (1979) also stated that routine tools in chronobiology. [2, 33, 34] (Figure 3) social life infinitely fluctuates by periodical movements. [39] Following in Matila Ghyka's (1881-1965) footsteps, Pius Servien (Pius Serban) Coculescu (1902-1959) focused on the Pythagorean logic and expression of rhythms, of as a fundamental psycho-esthetical element. [40, 41] For Constantin Radulescu –Motru (1868-1957), rhythms possibly derived from the “energetic personalism” circularity, whereas Lucian Blaga (1895-1961), almost «miraculated» by the dogmatic Aeon, recognized a historical rhythm. [42, 43] and interchangeably play with temporal manifestations the poet philosopher classified into ascending (“artesian”), descending (“cascade “) and horizontal (“river”) time. Constantin Noica (1909-1987) individualized multiple cyclic pulsations of the being: cosmic, spiritual, organic. [44] For the hermetic poet Ion Barbu, the skilled mathematician Dan Barbilian (1895- 1961), on the Number generating eurhythmics -“the music of the flying form”- the entire Universe would rely. In France, Marcel Proust (1871-1922) and particularly Henri Bergson (1859-1941) insisted on the relativity of and evaluation from one to another, from one person to another. [45] “The perception of change” between “duration and simultaneity’ would mark everybody`s “creative evolution”. Wondering “in search of lost time”, regular succession of time was Figure 3. Circadian variation of systolic blood pressure in clinically healthy pregnant women. Graphs show hourly abolished, whereas “remembrance of things ” forged means and standard errors. Nonsinusoidal shaped curves ones and engraved the present. Neither internal correspond to the best-fit waveform model determined by virtual, nor external real time was supposed to be population multiple-component analysis. Arrows point to physically explained and mathematically measured. After the peak time (orthophase) of the of blood opposing Einstein's ideas in 1911, Bergson accepted the pressure determined by the waveform approximation. concept of non-linear time. Temporal metamorphoses of (Hermida et al, 2004)[34] human soul, body and mind usually dominate the

469 1st International Conference on Advancements of Medicine and Health Care through Technology, MediTech2007, 27-29th September, 2007, Cluj-Napoca, ROMANIA unquantifiable intuitive artistic creativity. Time, indeed, [15] Descartes R, [Passions of the soul], Ed. Ştiinţifică şi plays the friend and the foe of mankind, as Franz Halberg Enciclopedică, Bucureşti, 1984. ascertained. [33] Turning the zodiac wheel, the old of [16] Bernard Cl., [An introduction to the study of experimental days Chronos, master of ages, keeps on giving birth to medicine], Ed Ştiinţifică, Bucureşti, 1958. [17] Perreau-Lenz S., Pévet P., Buijs R.M., Kalsbeek A., The and devouring his own children, regenerating and Biological Clock: The Bodyguard of Temporal destroying, restraining and amplifying Nature's will and Homeostasis, Chronobiol., Int., 21; 1:1-26, 2004. gifts. [18] Goldberger AL. Is the normal heartbeat chaotic or homeostatic? News Physiol Sci, 1991, 6: 87-91. 15. CONCLUSIONS [19] Rensing L, Meyer-Grähle U, Ruoff P, Biological Timing and the Clock Metaphor. Oscillatory and Throughout the millennia, biorhythms were defined and Mechanisms, Chronobiol. Int, 18; 3:329-370, 2001. observed in order to preserve and restore health. A more [20] Amir A, Kobiler O, Rokney A, Oppenheim AB, Stavans J., sophisticated and precise identification and quantification Noise in timing and precision of gene activities in a genetic cascade, Mol Syst Biol, 3: 81, 2007. of chronomes, designating the sum of such periodic life [21] Prigogine I, [From Being To Becoming], Ed.Ştiinţifică, processes, was allowed by the conjoint progress of real Bucureşti, 1992. science-based concepts and techniques applied to [22] Gamow G., [30 years that unsettled physics], Ed biology. Chronomedicine aims now at implementing Ştiinţifică, Bucureşti, 1969. time-scheduled investigations and therapies meant to [23] Flad J-P, Les trois premières machines à calculer: Schick improve human condition under both physiological and ard (1623), Pascal (1642), Leibniz (1673), Paris, 1963. pathological circumstances. Living organisms display [24] Karbo M, Architecture PC: théorie et pratique, Compéten time-machine features. This whole-life gradual and/or ce Micro, No. 35, Paris, 2005. instantaneous is irreversible, constantly [25] Chorayan O G, Neurocybernetics: contents and problems, Kybernetes, 29, 5/6: 803 – 810, 2000. revealing the horizon immutable , the anthropic [26] Berlekamp E.R., Conway J., Guy R.K., Winning Ways for and the entropic principles, the special spacetime Your Mathematical Plays, Academic Press, London, 2001 geometries and the general relativity of things. 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