CENTENNIAL OF RADIOBIOLOGY: ON THE 150TH ANNIVERSARY OF I.TARKHAN-MOURAVI (TARCHANOFF)'S BIRTH K.NADAREISHVILI ABSTRACT. The article is devoted to the life, scientific and public activity of renowned Georgian scientist I.Tarchan-Mouravi (1846-1907), the author of a number of known discoveries in the field of biomedicine, including skin-galvanic reflex (Tarchanoff's reflex). To him belong also pioneer studies in the field of biological action of X-rays, the results of which were published several months after the great discovery of William Konrad Roentgen, and were devoted to the problems of neuroradiobiology, radiation embryology, radioecology, etc. Being a century old, many problems explored by him are still of great topical interest. "It is my firm belief that there is no science for science... All that exists should become the subject of study for science and all achieved by science should be realized in life". These words of the distinguished naturalist Ivane Tarkhan-Mouravi (Tarkhanoff) pronounced at the end of last century not only preadmire our time when science has become a productive force, but also figuratively characterize the entire creative and public activity of a scientist whose motto was "science for life, life for science"... [1-3]. Ivane Tarkhan-Mouravi was born on June 15, 1846 in Tbilisi in the family of a general of Russian army, great grandson of the Georgian national hero Giorgi Saakadze - Didi Mouravi (Great Governor) who had been awarded the title of prince and become tax-free for his great services to his country. Thence comes the double name borne by the descentants of his only son Siausha who had miraculously survived and not shared the fate of his brothers. Scientist to be, still in childhood, was distinguished by his endowments and exclusively attractive appearance. This is testified not only by his personal archives, and correspondence of that time, but also by press. Already at the age of 10-12 except his mother tongue and Russian he perfectly well knew a few European and Caucasian languages. Alexandre Dumas (Dumas pere) on his journey to the Caucasus paid a visit to the family of Ramaz Tarkhan-Mouravi, the governor of Nukha region and devoted some chapters of his book "The Caucasus" to the rapturous description of his friendship with little Ivane. Here is what he specifically wrote about him: "The boy sowed excellent knowledge of the French language... I was amazed at hallicism in the speech of the boy... It was miraculous and I was charmed by him... I don't even dare call him a child... When I extended both hands to say farewell, the little Prince began to weep: Then I pulled him up and embraced him as my own son. Parting with little Ivane has inflicted me the most severe pain throughout my stay in "The Caucasus" [4]. Cultivation of I.R.Tarkhan-Mouravi's talent has been much promoted by manyfaceted primary education and cares of his father who having early become a widower, dreamed of a brilliant military career for his son. To this end, he took him to St.Petersburg, but intellectual curiosity of the fellow and his keen interest in natural sciences induced his father to give consent to his physico-mathematical education at the University against the son's strife to be a doctor. However, a year later together with N.N.Miklukho-Maklai and other students, having later on become distinguished personalities of Russia, he was expelled from St.Peterburg University for the participation in students' meetings and "free-thinking". Nevertheless, I.R.Tarkhan-Mouravi thanks to his authoritative father and relatives was allowed to continue his higher education in Rissia. He immediately starts preparations for his dream to come true and in 1864 becomes a student of the Imperial Medico-Surgery Academy. Still being a student, he starts to pursue experimental work in the field of Physiology under supervision of I.M.Sechenov, publishes papers and two years after graduation from the Academy in 1871, defends doctoral thesis on "The effect of heat and cold on the sensitive nerves of the spinal cord and cerebrum in frogs". He survived throughout his life this interest in the questions of action of various external physical factors on physiological processes in a broad ecobiological aspect. He has made a number of interesting discoveries which are still topical. After defending doctoral thesis he pursued research in the leading institutions in Germany, France, Italy, Austria, etc., publishes independent and joint works with outstanding physiologists of these countries. Apart from physiological laboratories of Holtz and Claude-Bernard, he worked hard and had success in biochemical laboratory of Hoppe-Zeiler, in a Cytomorphological Laboratory of Ranvier, etc. This was prompted by his aspiration to make manyfaceted complex research of physiological processes, gain insight into the physico-chemical mechanism and morphological basis of the phenomenon of life. Upon arrival from prolonged missions abroad, he not only published scientific papers and installed all new, but also widely popularized, achievements in the world science of his time. In 1875 he was elected private dozent, in 1877 - professor, head of chair of physiology at the Imperial Medico-Surgery Academy and in 1881 at the age of 35 he is a full member of the Academy, Scientific Secretary. Exclusively omniferious are the scopes of research, pedagogical and public activities of I.R. Tarkhan-Mouravi. Neurophysiology and rehabilitation, problems of social and professional Sanitary, physiological bases of hypnotherapy and psychophysiology, evolutional physiology and roentgenotherapy, plant physiology and radiobiology, microcirculation and hormonotherapy, ecology and balneology, hematology and social aspects of medico-biological problems - this is hardly a complete list of areas of natural sciences wherein the scientist's inquisitive mind and width of thought found their embodiment in innumerous discoveries and epochmaking research. A great number of papers and scientific-biographical investigations [1, 5-13, etc] have been dedicated to the life, research, pedagogical and public activities of I.R.Tarkhan-Mouravi. However, many of his discoveries, having become classic, are known to the majority of contemporary biologists and physicians not in association with the author. There is some fault for it of the author himself: the phenomena discovered by him were so much laconically, figuratively and essentially determined that the author remained in shadow. Suffice it to mention skin-galvanic or psychogalvanic reflex. It is hardly possible to name the fields of biology and medicine where this phenomenon has not been employed as one of the criteria or tests. The relevant device is being serially manufactured, yet not all know that this discovery belongs to I.R.Tarkhan-Mouravi. Tarkhanoff reflex appears to be one of the many findings in the field of neuro- and psychophysiology bringing to the author worldwide fame [14]. Now let's take research in the field of microcirculation. In the late 19th century the idea of the structure, regulatory mechanisms and biological significance of this region of vascular bed was far from the truth. The author of theory of cellular pathology Rudolf Virchow regarded that the stellate cells and fibers of connective tissue contain hollow spaces directly associated with the lumen of blood and lymphatic vessels, in the system of cavities he assigned a crucial role in feeding the cells and tissues "Serous vessels" through which conduction of only plasm and lymph without formed elements was admitted were believed to have a crucial role in realization of nutritive function in blood- and lymphformation, they were accepted as a conjunctive link of these systems both between each other and with the intercellular space. It is of interest that these ideas were based on "convincing histological findings". In the handbooks and textbooks of that time were described the schemes and mechanisms of functioning of this "triple relation". And in 1875 in Parisian Journal of Normal and Pathological Physiology, and later in a number of journals of Russia and European countries I.R.Tarkhan-Mouravi publishes a series of morphophysiological investigations which fundamentally alters the then available views, once and forever resolving this problem. He discovered that between the blood- and lymphatic vessels there are no direct anatomical connections, nor is between these systems and intercellular space. It was such a big landmark in physiology that enabled to characterize it as the transition from the level of knowledge of Harvey to the current view of the vascular system [15], embracing the period of almost half a millennium. In the given paper we have no possibility to consider even the basic physiological studies by I.R.Tarkhan-Mouravi. However, one cannot help emphasizing one exclusively important feature of the entire scientific activity of the distinguished scientist. Any physiological, general biological or psychological phenomenon, once it had fallen into the scope of interests of I.R.Tarkhan-Mouravi, not only found a comprehensive treatment on the basis of cummulative knowledge in the most diverse fields of science of that time, but also received manyfaceted evaluation and detailed analysis from the point of view of practical medicine and health care. To illustrate the above statement one may give examples related at least to some of the discoveries that had been dealt with above. Pioneer of skin-galvanic reflex has employed it as a diagnostic and psychophysiological test in the most diverse diseases, detecting not only its genuine clinical value, but also perspective of this method in all those areas of medicine where it is so widely applied nowadays. In psychology and physiology of emotions these fundamental investigations proved to be epochmaking [10,11,16,17]. Extremely intriguing seems retrospective analysis of works by I.R. Tarkhan-Mouravi from present-day position, the so-called reflexotherapy; as regards his discoveries in the field of microcirculation, in this aspect, noteworthy are the facts of disturbance of structural intactness and permeability of closed systems of lympho- and bloodcirculation, found by him in inflammatory and other pathological processes. A propos, it was during inflammation that he had revealed the effect of reflex enchancement from the periphery (peritoneum, mucosa, skin) on the cardio-vascular system and other vegetative functions, made comprehensive assessment of the significance of this hyperactivity in pathogenesis and formation of symptoms of a number of diseases. In current literature, unfortunately, it is rarely mentioned that some of the fundamental clinical theses of S.P.Bodkin are based on experimental findings of his friend I.R.Tarkhan-Mouravi in the field of applied physiology and general pathology. Naturally, not all the problems tackled by I.R.Tarkhan-Mouravi lead to brilliant discoveries.There was success and failure, enthusiasm and disappointment, but persistent search did not cease.Moreover, any at first sight unsuccessful experiment was subject to such a detailed assessment that there sprang out new projects, new prospective trends of research, new generalizations and strikingly astute basic ideas. Here is one of the many characteristic examples. It is commonly known what a huge resonance had the discovery by P.Zion and K.Ludwig of the depressor nerve of aorta. After reiterative discussion with S.P.Bodkin of the commonly accepted point of view concerning the role of depressor nerve as a single mechanism preventing the development of hypertension and some other disorders of the cardio-vascular activity, I.R.Tarkhan-Mouravi pursued search of the ways for the creation of an experimental model of cardiovascular pathology. In chronic experiments, that per se were rather a rare event in that time, by means of transection and prolonged chemical stimulation of the depressor nerves he made an attempt to reproduce in rabbits hypo- or hypertension similar to clinical forms. Study of the physiological mechanisms related to depressor nerves might also serve as an example that T.R.Tarkhan-Mouravi followed scientific trends of Chair of Physiology at St.Peterburg Imperial Military-Medical Academy started by P.Zion, who had headed chair before him. However, in his experiments many general conclusions associated with the name of his predecessor at the Chair have not proved to be right. Though perennial search continued, no publications appeared. Only in 1882 in supplement to M.Foster's handbook he submiited some findings on the normal development of rabbits subject to bilateral transection of the depressor nerves and summarized his observation in the following way: "Function of the depressor nerves is thus a frequent occurrence of depressive influences rather spread in the body and without which the rabbits organism can do well with impunity" [18]. Only half a century later Hering discovered another nerve subserving, in addition to other functions, depressor function as well. As to the depressor reflexogenic zones and respective nerves in other regions of the vascular bed and in the heart itself, they were discovered considerably later. Only retrospective analysis of similar facts and astute conclusions of I.R.Tarkhan-Mouravi in the most diverse fields of natural science would call for special study. Particularly valuable gift in I.R.Tarkhan-Mouravi was his keen interest in the search of novel on the junction of various disciplines, his ability to react to achievements and discoveries almost in all fields of science of his time, his persistence to make use of recent data for the resolution of topical tasks of practical medicine, biology, his commitments to promote social progress through the popularisation of scientific knowledge. One of the characteristic examples of this kind is radiobiology. As is known, in 1895 Wilhelm Konrad Roentgen for the first time informed about his outstanding discovery at the Christmas session of Vurzburg Society of Physicists. This sensational news spread very fast all over the world. In many physical laboratories equipment was feverishly made to reproduce experiment of Roentgen. Over 500 scientific and pseudoscientific communications have appeared for only one year. Mysterious X-rays stirred up increasing interest, since according to the information of the author of the discovery and his followers including physicians having observed the experiments, X-rays yielded reflection of bones and dense tissues on photofilms and fluorescent screen not eliciting any perceptions. Already a month later after this sensational news in research institutions of Russia similar investigations were started. The fact is noteworthy that on the initiative of the Society of Russian physicians and of St. Petersburg Biological Laboratory scientific reports were made with demonstration of experiments on physics of X-ray radiation and the question of its practical application for diagnostic purposes was commonly discussed. In spring of 1896 during discussion after similar lectures P.F. Lesgaft, who headed then St. Petersburg Biological laboratory, requested I.R. Tarkhan- Mouravi to express his view on the possible effect of X-rays on the process of life and suggested to carry out joint biological experiments. In his speech I.R. Tarkhan-Mouravi emphasized that it was necessary, first of all, to determine whether X-rays affected metabolism, the course of evolvement of animal and plant organisms and excitability of living organisms and tissues. This actually was the first research project with broad radiobiological targets and the scientist started its realization right away. In view of the fact that in physiological laboratories of the Russian Academy of Sciences where I.R.Tarkhan-Mouravi carried out his experiments there was no device for "obtaining X-rays" he decided to take advantage of summer holidays and work in physical laboratory where the device was available and free for his use. Having received permission from the authorities to work there and refraining from summer rest, I.R. Tarkhan-Mouravi convinced a physician L.K.Kulyabko to be his assistant in X-ray experiments. Preparation for the pending experiments was rather tense. By evidence of his contemporaries he took interest in everything related to X-rays, beginning with publications and newspaper reports in all European countries, including engineering questions of service and repair of the device "for obtaining X-ray", preparation of biological material, chemicals, etc. And in September of 1896 there appeared first results of the summer X-ray expedition as his interest in this problem was christened by a close circle of friends. Three papers appeared first in Proceedings of St. Petersburg Biological Laboratory [19], then in two issues of S.L. Botkin Hospital Paper [20, 21] where one can read: "...the present communication is, for aught I know, first attempt of the aspirant to prove that X-rays can be used not only for photographing and diagnostical purposes, as has been known so far, but they can also affect the course of vital functions... It would not be a wonder if in the near future X-rays would be used for curative purpose..." "Get a grasp of this lines. What is there in them? greatness or rather modesty", wrote in 1966 A.M. Kuzin [23] one of the leaders of Soviet radiobiology. Or, "his investigations have become kernel for studies on biological action of ionizing radiation. But it was only the beginning, birth of radiobiology". The basic radiobiological studies of I.R. Tarkhan-Mouravi, summarized in the same year of 1896 in a reprint [22], apart from containing the facts found by him for the first time, make an attempt to explain the mechanisms subserving the events observed. Naturally, from the current point of view some interpretations of these works seem outdated, but the objectives, project of further research and above all, methodological approach of the pioneer in the field of radiobiology are quite up-date. It must be borne in mind that all this happened only shortly after the discovery of roentgen, when disputable was not only the physical nature of radiation itself, but also the site of "discharge of X-rays" Tarkhan-Mouravi has not succeeded in studying all the questions and tasks posed by him in his papers, but his aspiration to radiobiology in the very broad sense, he preserved to the end of his life. From 1896 to 1908 over 30 papers devoted to the problems of radiobiology appeared in the Russian, German and French scientific and popular journals, 5 of them were published as separate offprints. Furthermore, in a number of physiological, sanitary and even social and journalistic papers of I.R. Tarkhan-Mouravi one can see parallels and arguments about X-rays and irradiation. The last work of I.R. Tarkhan-Mouravi that has been published after death of its author deals with radiobiology as well.Retrospective analysis of individual works by I.R. Tarkhan-Mouravi is hardly reasonable in the present paper, although some general views related to radiobiology might perhaps stir up certain interest. Methods of radiobiological investigations were thoroughly, in all details elucidated by the scientist already in the papers of 1896. In spite of their being 150 year old, even nowadays no claims can be made as to the detailed formulation of tasks and methodical realisation, except for accurate dosimetry which was then out of question. Not always, even in our days, one can read in radiobiological papers "each series with roentgenisation of animals was accompanied by control experiments, in which animals were kept quite under the same environmental conditions minus but X-rays... The only conceivable difference, hard to be removed... "in the opinion of Tarkhan-Mouravi, consists in heating the surrounding air and the biological subject. In this relation he carried out special experiments in which thermoeffect was expected to affect the radiation in different direction - either enhancing or impairing it. On the basis of those experiments he concluded that the biological effects revealed by him were not dependent on heating the object during "roentgenisation". A propos, this term, commonly employed until the recent time, had been introduced by I.R.Tarkhan-Mouravi. In the footnotes of his paper he wrote: "I'll thus refer to the process of exposure of the whole body or its parts to X-rays; the word "roentgenisation has the equal right to existance as "galvanisation". I.R.Tarkhan-Mouravi devoted so much attention to the methods of research that in the next year of 1897 he published a series of papers [24-27] dealing with the methods, techniques of roentgenography and experiment while working with Crookes tube. He suggested to use a special screen consisting of ground connected aluminium sheet coated with "lead paper". He thought that grounding was necessary in order to be protected from electrical action of X-ray source. The screen and experiments with X-rays were demonstrated by him to the meeting of biological community in Paris in 1897 [1,27] and he was perplexed by the fact that in France as well as in Germany and other countries, where he happened to be, they ignored shielding means while working on roentgen devices. The reason for this was, in his opinion, lack of knowledge about "physiological action of X-rays and incidence of development of skin inflammation among physicists and physicians. The latter, in his opinion, is far from being the most dangerous of possible consequences of irradiation with Crookes tube. I.R.Tarkhan-Mouravi was always keen on improving technically biological experiments and medical examination. He was the author of a number of novel methods including exsanguination method for the measurement of human blood volume, measurement of the velocity of "movement of nervous excitation", electrostimulation, etc. Perhaps not all know that still in 1878 he, for the first time, employed the telephone for neurophysiological studies [28, 29]. N.E.Wedensky [30] indicated that I.R.Tarkhan-Mouravi while currying out experiments with a telephone because of its poor quality could not directly "hear" biocurrents. But he devised a very interesting experiment. Through the examined object he passed weak current with the frequency 500Hz which did not cause any stimulation but was distinctly heard on the telephone. Potential of the nerve or muscle was modulated by loudness of this tone depending on the polarity of "action currents". It was perhaps not difficult at all for the scientist, who was a refined musician-violinist,to pick up these shifts. This is evidenced by his findings in the field of nervous-muscular physiology that cannot only be accounted for by the current concepts, but also are impecable from the descriptive point of view. Moreover, biophysical and physiological interpretation of his findings are authentic [10]. I.R.Tarkhan-Mouravi had never been infatuated by the method for the sake of method. Every methodical novelty including novelty in radiobiology, was prompted by his intention to gain insight into the mechanism of a biological event, approach the multiaspect resolution of medico-biological problems from the position of a naturalist and a citizen striving to put scientific achievements to the service of community. As an example may serve departments of rational catering of population, emergency medical aid for plague and plague vaccination, etc. organised by him at the world exhibition in Paris in 1900. "For this he was awarded order of a Legion of Honour", "Animal behaviour under X-rays". This is the heading of the first radiobiological scientific section [19]. It is quite natural that I.R.Tark:han-Mouravi begins stating the results of his observation with the most common physiological test. This is the basic principle of his world view - always crave to conceive biological expedience of any behavioural act, any motivation [9-11]. He found that "roentgenisation for a quarter of an hour " had a "calming effect" in frogs causing a dramatic reduction of general motor activity. This effect was confirmed almost a century later. X-rays had a similar effect in flies and butterflies. However "upon approachment of Crookes tube the animals manifest anxiety, become excited and assemble in those sites of the glass vessel where silent electrical discharges and X-rays cannot reach". SimIlar effect of radiation "escape" in various animals was rediscovered but half a century later [31], while the significance of electrical and electromagnetic fields attending the generation of X-rays which is referred to by I.R.Tarchan-Mouravi as "silent discharges" and "electric action of Crookes tube" was ascertained only in the 60s of this century [32]. Naturally, there was then no notion of the dose rate. Approachment of the source of radiation to a biological object the scientist considered as the cause of appearance of "unheard" or "silent" discharges, likewise the appearance of electrical discharge when two adversely charged bodies are drawn nearer. In the publications of 1896-1897 a decisive role in the "escape" effect, "calming" and "stimulating" action of X-rays" had been attributed to the electrical effect of Crookes tube. He regarded that this effect was dangerous for man and animals. All this led to the development and persistent propaganda of protecting screen, that has been spoken of above. In the same year appeared his papers on the "electrical effect of Crookes tube"... [2, 26] where in addition to the questions of a possible mechanism of "escape","calming" and "stimulating" effects, it is conjectured by Tarkhan-Mouravi that skin inflammation and hair fall-out, except for X-rays, may be caused by the action of electric field on vital processes. In more details these issues had been discussed in his numerous works that appeared after the discovery of radioactivity, while in his paper "Physical energies of nature as having curative power" [33], published as back as in 1898, to the number of external stimuli, apart from mechanical, clinical, thermic, photic and electric, the scientist attributes also ionizing radiation not associating this action with the "electrical" one or with "silent discharges". Making an attempt to explain the physiological mechanisms of "escape" effect, calming or stimulating action of X-rays" and "physical phenomena" attending the use of Crookes tube, the scientist based his views on the achievements of almost all fields of natural science of his time and with the emergence of latest evidence or discoveries, radioactivity in particular, endevoured to evaluate their significance from the position of his own concept on the role of "physical events and natural forces in vital processes". This and many other of similar works may individually be considered from the position of physiotherapy and balneology. However, we restrict ourselves to stating here that bearing in mind the effect of X-rays on the metabolism, processes of evolvement and excitability, the scientist considered it reasonable to use ionizing radiation and in particular Crookes tube for the treatment of a number of diseases, especially of malignant tumors. This view was put forward and the author tried to substantiate it experimentally in his papers of 1896-1897. THE EFFECT OF X-RAYS ON ANIMAL'S REFLEX ACTIVITY Under this subtitle I.R.Tarkhan-Mouravi starts propounding his experimental data which in fact are his first attempts to comprehand the physiologied mechanisms of action of ionizing radiation on behavioral acts [19]. He found that exposure to X-rays for 15 min or longer both in intact and decapitated frogs caused a marked attenuation of excitability or a total suppression of acidic reflexes. In order to exclude the plausible effect of radiation on the receptor apparatus of the skin of extremity in one series of experiments the tested extremity was screened, while in another screening was made of the spinal cord. These experiments confirmed that "impairment of reflexes" after X-ray exposure depends neither on analgesia nor sensitive skin surface of the body, but on its moderating effect on the central nervous system itself. The same experiments have demonstrated that during X-radiation of the exposed spinal cord the suppression of Turk's acidic reflexes is far more stronger, for, in this case, conditions are "more favourable for the X-rays to penetrate into the spinal cord". On the basis of these experiments it has been inferred that the changes in animals behaviour, described above, are due to the action of radiation on "irritability", reflex activity of animals. It should be emphasized that in these experiments the scientist found individual divergence in sensitivity to X-rays, as well as the significance of the initial level of"irritability" and he made an attempt to explain the biological mechanisms of these events. Moreover, in 1896 he for the first time posed a hitherto topical problem of modifying the effect of radiation exposure by physiologically active substances and, what is especially important, the problem of alteration of reaction of biological systems of the irradiated body to the action of a variety of pharmacological drugs. In this respect experiments with the application of strychnine dealt with in the section "Roentgenisation and strychnine tetanus" deserves attention. I.Tarkhan-Mouravi found that after injection of 4-50 mkg strychnine sulphate into the spinal lymphatic duct in the 15-30 min irradiated frogs seizures either did and develop at all or were quite faint.while controls often perished from "strychnine tetanus". It should be noted that experimental and control animals in this case, were selected by their weight, sex and colour of skin. Control experiments were also carried out with irradiation of strychnine solution itself. The scientist noted that "the strychnine solution itself exposed to X-rays did not at all change its poisoneous power" and that "antiseizure effect of X-rays is due to their action on the animals" [19]. Similar "antiseizure" effect was observed if strychnine was introduced just before irradiation or after it, on the face of appearance of first sings of seizures. These experiments lent support to the conclusion that "thanks to a decline in excitability of the CNS under X-rays one can fight, to certain extent, against the burst of strychnine tetanus [19]. It should be emphasized that these experiments served as a basis for a further search of means modifying the radiation effect, and of physiological mechanisms for changing reaction of the irradiated body to pharmacological drugs and hormones. Not going into details of retrospective analysis of this issue, it could be only stated that these endevours had prompted Tarkhan-Mouravi to suggest in 1905 a method of combined application of roentgenotherapy and so-called organotherapy [34, 35]. In the works "On theoretical basis of helpful combination of roentgeno- and sperminotherapy" published in 1908, already after the death of the scientist [36] one can come across censure on this issue that are in tune with the times. In the experiments with strychnine there is one more, in our opinion, very important aspect. It as already one hundred years that the question of the so-called stimulating or excitatory action of ionizing radiation has been studied, but it is still the point at issue. Even the assumption could not be disregarded that there are specific ionizing radiation receptors, not speaking of other plausible triggering mechanisms from receptors of different modalities up to gustatory bulbs and association areas of the cortex. In order to resolve this question almost the whole uptodate methodical arsenal has been employed. Yet in none of many a work of this kind was an attempt made to analyse findings of I.R. Tarkhan-Mouravi who, as back as in 1896, resolved the question with a witty and convincing method. By means of strychnine injection he caused enhancement of excitability and against this background exposed frogs to short-lasting X-rays. It was discovered that "...the onset of short-term roentgenisation coincided with the burst of tetanus, and this recurred sometimes several times in succession". Further he writes: "I am firmly convinced that these coincidences are not occasional and that at definite extent of enhancement of reflex irritability a sudden fall of X-rays may serve as a stimulus..." [21]. If in the paper published in Proceedings of St.Petersburg Biological laboratory [19] Tarkhan-Mouravi considered "silent discharges" and electrostatic effect of Grookes tube as the cause of animal's avoidance of radiation and its exciting action, in his work [21] published two months later in the same year (1896) he writes: "all doubt about the interference in these experiment of silent electrical discharges of Grookes tube or mechanical oscillations and the liking must be excluded, since the relevant precautions have been taken against the interference of all these factors in the described event" (p.789). Thus, according to I.R.Tarkhan-Mouravi, X-rays acting on "irritability", increasing or decreasing excitability of nerve cells depending on the "intensity of roentgenisation and time elapsed after its completion", may themselves be stimulus, but for a distinct manifestation of this effect it is necessary "to increase irritability by strychnine". He is biased to regard that "without strychnine X-rays can exert stimulating effect through the "central nervous acts" accounting for the above discussed behavioural reactions to irradiation and some other changes in "reflective activity" by X-rays. However, in the papers of 1896 describing "the effect of X-rays on the colour of skin of Rana temporaria" he considers that the question is not clarified yet and is in need of further study.I.Tarchan-Mouravi paid attention that irradiated frogs, including those "strychninized before or after exposure to X-rays", ... "being then placed in light and in water, in an hour or two acquire vivid dark colouring, depending, of course, on relaxing and widening of pigment cells of the skin. This phenomenon usually disappears on the second or third day. It has not been clarified yet whether it depends on the direct effect of X-rays on the periphery of body, or is a result of the central nervous act..." [19]. In his later papers Tarkhan-Mouravi several times reverted to this issue and was prone to consider most of neuroradiobiological effects, revealed by him, as a consequence of preferential direct "moderating" action of radiation on the CNS. EFFECT OF X-RAYS ON THE HEART AND BLOOD CIRCULATION I.Tarchan-Mouravi explored a variety of subjects, wishing to cope mainly with two tasks. On the one hand he was interested in the questions of reaction of myocardial and smooth muscle cells, as well as nervous elements that regulate the cardiac activity and adequate blood circulation to tissues.On the other hand, he hoped to check in these experiments his hypothesis about chemical nature of the effect of X-rays on the physiological processes that are underlied by primary processes of absorption of X-rays by the cell lipids. Activation of metabolism, in his opinion, should lead to enhancement of heart rate and intensity of cardiac contractions, an increase in blood flow in vascular vessels, while during inhibition of metabolism an inverse picture must be observed. However, experiments with irradiation of extirpated beating heart of frog in situ, as well as of vessels of the tongue and mesentery did not yield the expected results. The effect could not be detected either during whole-body irradiation of animals or irradiation of isolated regions of ciliated epithelium. He endevoured to resolve these points also from the position of general biology, irradiating a variety of subjects, including higher plants and water plants, observing the effect of X-rays on "sap flow in the cells of Vellisneria spiralis", etc but in all cases a negative result was obtained, i.e. X-rays had no effect on these physiological processes. Navertheless he did not renounce his hypothesis, regarding that the equipment he used was not "powerful enough" to detect the effect. He writes that all the effect of X-rays from Crookes tube, used by them, is "restricted by the sphere of CNS in relation to which X-rays play a role of moderating, retarding agent" [19, p.51]. The same view was advocated in another paper [21] published in 1896, where he writes that "their preferential, if not exclusive action X-rays direct towards cerebral nervous centres" (p.786). This point of view having but a historical importance cannot be encountered in his works published since 1896. Moreover, under "moderating" or "retarding" action he meant inhibition or suppression of physiological processes in cells. For the illustration of the afore-said one may give the following example. The Effect of X-rays on the embryonic development, as is known, has been first studied on the fertilized eggs of lampreys. "Intermixing and dividing at random into approximately two even parts the lampreys' eggs fertilized at one go, one lot was every day subject to 1/4 h exposure to X-rays twice a day, while the other, control one was left in the same section of room under equal conditions of lighting and temperature. A single thoroughly done experiment yielded that unexpected result that from the lot of roentgenized eggs a single animal was thatched, while from the control - several dozens" ([20] p.755). The scientist considered this result so much important that in summary of his works of 1896-1897 [20,21,27] with X-rays, he emphasized the necessity of further carrying out similar experiments on a variety of subjects. After the discovery of natural radioactivity I.Tarchan-Mouravi right away began to think "On the role of radioactive beams in biology and treatment of diseases. However, he could get radium for his physiological experiments" only after his visit to Paris at the World exhibition. In 1902 in the letter to his friend Ch.R.Richet he complained that "radium was too little" and he could not complete experiments in the same subject as had been carried out with X-rays. In 1903 he published three communications under a common heading quoted at the beginning of this paragraph [37]. In these papers, about 50 pages, the author makes an attempt to evaluate the evidence reported in the literature and his own observations in a wide aspect of general biology, as well as practical aspects of the use of natural radioactivity in medicine and agriculture. They were followed by publication of scientific and popular papers concerning the effect of radium beams on various biological processes and organs in animals [38-43]. Getting familiar with these works one can not only judge about the author's great pursuits of the problems of biological action of ionizing radiation, but also understand the reasons for his persistent research in this field. On the one hand he hoped that while studying "...changes in physiological processes, evoked by natural and artificial active rays, there opens up a possibility of unveiling and cognition of the essence of vital processes", and on the other hand, "to use irradiation for the purpose of solving important practical tasks in health care, agriculture, etc." As a characteristic example can serve a joint paper of I.Tarchan-Mouravi and F.Mauoldenhauer [44], published in the Bulletin of Krakov Academy of Sciences.Later on the paper has been translated from French into English with brief comments ([1],p.180-185), however, in radiobiological, in particular in phytoradiobiological literature these findings, unfortunately, have never been considered. This work entitled "On natural and artificial radioactivity of plants and its role in their growth", is a result of a number of long-lasting experiments, as indicated by the author, "on germinating seeds and the plants themselves in various periods of growth". The basic findings of the authors, and even some aspects of their scientific interpretation appear to hold a certain interest from the point of view of uptodate phytoradiobiology. Here are some of them. 1. According to the data of I.R.Tarchan-Mouravi and F.Moldenhhauer, germinating seeds of pea, as well as cereals - wheat, barley, oat, rye, etc. after exposure to radium emanation, the method described elsewhere [35], "become obviously radioactive, that is evident from their ability of discharging electroscope and affecting the photographic films. One pole of the seeds appear always more radioactive than the other. It is just the pole where root of future plant develops". In view of the fact that the exposure to radiation occurred in water by means of circulating in the air containing radium emanation, the authors make a conjecture that the radioactive substance is incorporated into the developing cells of the plant, but after several days this "induced radioactivity" again recovers the "initial level of natural radioactivity of seeds". Similar data were obtained in young plants, including the effect of radium bromide on different parts of plants. The authors prove that the "induction" of radioactivity occurs largely in the roots, and, thence "it is reduced progressively ascending to the leaves and blossoms". Natural radioactivity in germinating seeds is also concentrated in the roots. By exploring dry seeds, straw and roots, as well as the effect of high temperature, it was established that radioactivity in plants "is merely a physical phenomenon" and "is not a vital phenomenon. Radioactivity in plants they associate with the radioactivity of soil and give as an example the results of their study of medicinal herbs grown in Tsarskoe Selo. The authors write: "Analysing these medicinal herbs, we always find them more radioactive than those cultivated in other less radioactive soils". "There naturally arises a question whether radioactivity has any role to play in the life of plants, in their development". I.R.Tarchan-Mouravi considered that the answer to this question was the matter of future, but at the same time he brings up some examples of the so-called stimulating effect of radiation on the organism of animals and plants. Curative effect of radioactive baths, acceleration of development of eggs of a variety of animals (experiments by A.Baume), ability of radium of causing, at a certain stage of incubation partanogenesis, experiments with the cultivation of plants in the radioactive soil, yielding "wonderful results by rich crop of the obtained culture", etc. I.R.Tarchan-Mouravi considers that small doses of radiation has a stimulating effect on the cells of animal's and plants' organism, while inhibition of development of fertilized eggs, development of radiation ulcers, falling out of hair, etc. he considers as a result of disturbance of chemical bases of vital activity of the cells at the expense of absorption of radiation by the lipids of cellular sheath, organels and nuclei. In his last work "On theoretical basis of usefulness of combination of roentgeno- and sperminotherapy", analysing general biological aspects of "stimulated and inhibited, enhanced and decreased resistance" of the organism, etc. under the effect of various physical powers of nature, I.R.Tarchan-Mouravi advanced a number of novel ideas and devised concrete plans for experimental resolution of these theoretical questions in the light of requirements of practical medicine of that time. He proves that the events observed at roentgenization feeling of indisposition, headaches, cardiac weakness are due to the formation as a result of radiation of various "poisonous substances", including neurine and choline. Spermin, being, in his opinion, a catalyser "converts these poisons into harmless compounds". The project of future investigations in this direction he failed to realize. I.R.Tarchan-Mouravi died at the age of 62 before this paper was out of print. Russian intelligentsia paid tribute to its distinguished representative. Burial service took place at Alexander-Nevski lavra. At the burial ceremony an obsequial address was delivered by I.P.Pavlov who succeeded him as head of Department. He was also chairman of ad hoc session of Society of Russian Physicians, in memory of I.R.Tarchan-Mouravi. Similar sessions were held in other cities of Russia. In the newspapers, scientific journals and other popular publications appeared long obituaries describing the manyfaceted research and pedagogical activities of the distinguished physiologist, an honorary member of physiological societies of Paris, Vienna, London, Rome, New-York and other research centres. In 1908 a sculpture of I.R.Tarchan-Mouravi was erected at the Pasteur Institute and in 1912 I.P. Pavlov chaired the ceremony dedicated to the opening of stele at his tomb.
Monument to I.Tarkhan-Mouravi in front of State Medical University in Tbilisi. Great is the contribution of I.R.Tarchan-Mouravi to popularizaton of the scientific of his knowledge time, organization of women's society in Russia, propaganding the cultural heritage of his time. He was a close friend of leading feagures in Russian science: D.I. Mendeleev, I.M. Sechenov, S.P. Bodkin and others, was in friendly relations with the honour of Russian literature A.P.Chekhov, a great writer A.M.Gorki, a great artist I.E.Repin, who made a several splendid portraits of the scientist. Potocopy of one of them is presented on page 1. In the history of Georgia, its science and education I.R.Tarchan-Mouravi has a special place. He was one of the bonds through which European culture was brought within the reach of the Georgian people oppressed by autocracy. He sought the ways of social progress and release from the tsarist yoke. The duty of Georgian scientists is to make immortal the name of the great scientist and public man not only by erecting monuments to him, naming the societies and streets by his name, granting scholarships and awards, but also by omniferious development of those fields of science the pioneer and founder of which was I.R.Tarchan-Mouravi (Tarkhnishvili). This is olso important allowing for the prospects of further development of radiobiology[45, 46]. At the present time two specialized radiobiological institutions are functioning in Georgia: Scientific Research Centre of Radiobiology and Ecology, Georgian Academy of Sciences ( 51 Telavi St. Tbilisi, 380003, Georgia; +995 (8832) 942-017; 943-209; 775 442. FAX +995 (8832) 936 126. E-mail: kiazo@caucasus.net) and Institute of Agricultural Radiology, Georgian Academy of Agricultural Siences (383409, Mtskheta, Zagesi,Georgia; +995(8832) 943-146; 624-608; 624-645; 625-133).
At the Centre functios: The Georgian National Council of Radiation Research, the Georgian Academy of Ecological sciences and Bio-Medical Engineering Society of Georgia. The Center publishes 3 Colections of Works: "RADIATION STUDIES" (published since 1971, Vol.9 is now in press), "BIOMEDICAL TECHNIQUES" (published since 1972, Vol. 11 is now in press) and "PROBLEMS OF ECOLOGY" (since 1990, Vol. 3 is now in press). Scientific-Research Institute of Agricultural Radiology is the foundation of the Georgian Academy of Agricultural Sciences. The work pursued now at this Institution is in the following trends:
Notwithstanding the difficulties created in the postsoviet period, research in the field of radiobiology in Georgia is in progress and there is a tendency to extending the collaboration with the colleages of other countries. R E F E R E N C E S 1. K.D. Eristavi, E.M.Semenskaia. "I.R. Tarkhnishvili: life, scientific and public activity". Georgian Med. Publ. Tbilisi, 1953, p.78. 2. Academician I.R.Tarchanoff (obituary). Newspaper "The New Time", No 1145 of 13 Aug. 1908, p.4. 3. In: Academician I.R.Tarchanoff. Popular Medical journal of Dr.Ochs, No 8, 14-16, 1908. 4. A.Dumas. The Caucasus. Journey of Alexandre Dumas. Transl. by Robovskii, Part 2, Tiflis, 1861. Chapters 3-33. 5. I.R. Tarchanoff - physiologist. Big Encyclopedia vol. 17, p.301, Education, St.Petersburg, 1905. 6. N.O.Cybulski. Prof. Dr. Kniaze Ivan Tarchanow-Mourawow. Gaz. Lekarsky (Wars.), Ser. II, 28, n 52, 987-992. 7. I.E.Repin. Letters of E.P.Tarchanoff-Antokolskaia to I.R.Tarchanoff. Publ. House "Art", Leningrad, Moscow, 1937. 8. K.Sh.Nadareishvili. Ivane Tarkhan-Mouravi.130th anniversary of his birth. Radiation Studies, Tbilisi, 1978, v 3, 5-28. 9. S.Sh.Avaliani. Philosophical views of I.R.Tarkhnishvili. Publ. House of Acad. Sci. Georgian SSR, Tbilisi, 1957. 10. N.N.Dzidzishvili. Neurophysiological works of I.R.Tarkhnishvili. In: Scientific heritage of I.R.Tarkhnishvili (Tarchanoff). Publ. House of Acad. Sci. of Georgian SSR, Tbilisi, 1962, p. 49-72. 11. O.I.Tabidze. In: Scientific heritage of I.R.Tarkhnishvili (Tarchanoff). Publ. House of Acad. Sci. of Georgian SSR,Tbilisi,1962, p.73-94. 12. A.N.Bakuradze. Physiology and pathology of digestion in the works of I.R.Tarkhnishvili and his pupils. In: Scientific heritage of I.R.Tarkhnishvili (Tarkhanov). Publ. House of Acad. Sci. Georgian SSR, Tbilisi, 1962, p. 117-126. 13. M.M.Zaalishvili. I.R.Tarkhnishvili's works in radiobiology. In: Scientific heritage of I.R.Tarkhnishvili (Tarchanoff). Publ. House of Acad. Sci. Georgian SSR, Tbilisi, 1962, 127-130. 14. I.S.Beritashvili. Opening address at the jubilee session dedicated to 50th anniversary after the death of I.R.Tarkhnishvili (Tarchanoff). Publ. House of Acad. Sci. Georgian SSR, Tbilisi, 1962, p. 5-8. 15. G.I.Mchedlishvili. Studies of I.R.Tarkhnishvili in the field of physiology of blood circulation. In: Scientific heritage of I.R.Tarkhnishvili (Tarchanoff). Publ. House of Acad. Sci. Georgian SSR, Tbilisi, 1962, p. 107-116. 16. B.I.Ananev. Essays on history of Russian psychology in the 18th and 19th centuries. Moscow, 1947. 17. V.P.Gorev,M.V.Gjuter. Experience and perspectives of application of Tarchanoff phenomenon. Rep. VII All-Union Congress of Physiol., Biol. Pharmacol., 1947, p. 643-645. 18. I.R.Tarchanoff. Development of animals deprived of depressor nerves. In: Handbook of physiology by M.Foster, St.Peterburg, 1882, p. 643-645. 19. I.R.Tarchanoff. Experiments on the action of Roentgen X-rays on the animal's organism. Proc. St.Peterburg Biol.Lab.,1-3, 4752, 1896. 20. I.R.Tarchanoff. On physiological action of X-rays on the central nervous system. (Preliminary Comm.). S.P.Bodkin Hospital newspaper, Nl 33, 753-757, 1896. 21. I.R.Tarchanoff. On physiological action of X-rays on the central nervous system (end), S.P.Bodkin Hospital newspaper, No 34, 785-791, 1896. 22. I.R.Tarchanoff. On physiological action of X-rays on the central nervous system. St.Peterburg, 1896. 23. A.M.Kuzin. Radiation exploration. Newspaper "Komsomol Truth" of 29 May,1966,p.3. 24. I.R.Tarchanoff. The way Crookees tube ought to be used while protographing by X-rays various parts of the body. (1st preliminary comm.) S.P.Bodkin Hospital Newspaper, No 13,457-459. 25. I.R.Tarchanoff. Electric action of Crookees tube causing excitation of animal tissues (2nd and 3rd comm.), S.P.Bodkin Hospital Newspaper, No 13, 459-466, N 27, 1009-1014, 1897. 26. I.R.Tarchanoff. Electric action of Crookees tube causing excitation of animal tissues. St.Petersburg, 1897. 27. I.Tarchanoff. Actions physiologiques des tubes de Crookes a distance. Compt. Soc. de biol., 49, 740-743, 1897. 28. I.Tarchanoff. Das Telephon als Anzeiger der Nerven und Muskelstrome beim Menschen und der Thieren. St.Peterb.Med.Wschr6., N 43, 353-354,1878. 29. I.Tarchanoff. DasTelephon im Gebeite der thirischen Edestritat. St.Peterb. Med.Wschr., N 11,93-95, 1879. 30. N.E.Wedensky. Telephone observations on electrical studies in muscular and nervous apparatus. Trans. St.Peterburg Soc. Naturalists, 14, 1, 5-6, 1883. 31. D.Kimeldolf, E.Hunt. Action of ionizing radiation on the function of nervous system. Moscow, 1969 (Russian translation). 32. M.N.Livanov. Some problems of the action of ionizing radiation on the nervous system. Moscow, Med. Publ. House, 1962. 33. I.R.Tarchanoff. Physical energies in nature as curative powers. Encycloped. Survey, 1, 351-366,1898. 34. A.V.Poehl, I.R.Tarchanoff. Combination of roentgenotherapy with organo-therapy. J.Med.Chem., No 34/35, 171-189,1905. Reprint, St.Peterburg, 1905. 35. A.Poehl, I.Tarchanoff. Die Kombination der Radiotherapie mit der Organo-therapie. Berl. Woschr., N 16, 457-560, 1905. 36. I.R.Tarchanoff. On theoretical basis of usefulness of combination of roentgeno- and sperminotherapy. J.Med. Chem., No 36/37, 49-51,1908. 37. I.R.Tarkhan-Mouravi. On the role of radioactive beams in biology and treatment of diseases. J.Med.Chem. of organotherapy, No 31, 1259-1276; No 32, 1299-1312; No 33, 1339-1356, 1903. 38. I.R.Tarchanoff. Action of radium beams on the eyes. Encycl. of Brocktause and Ephron, 37, vol.76, p.1211, 1903. 39. I.R.Tarchanoff. On the action of radium emanation on animals. Proc. and bibliographic selfeducation, No 29, 1121-1122, 1904. 40. I.R.Tanchanoff. Recent news of radium. Proc. a. Bibliogr. Selfeducation, No 7, 275-276, 1904. 41. I.R.Tarchanoff. On radium in the Caucasus. J. "Knowledge and Life", No 2, 28-29, 1905. 42. I.R.Tarchanoff. Action of radium on electric discharges of electric slope. J. "Knowledge and Life", No 78-79, 1905. 43. I.R.Tarchanoff. On radioactivity of mineral waters and springs. J. "Knowledge and Life", No 9, 150-152, 1905. 44. I.Tarchanoff et T.Moldenhauer. Sur la radio-active induste et naturalle des plantes et sur sou role probable dans la croissance des plantes. Bul. intern. de l'Acad. Sc. de Cracovie, N 1, 728-734, 1905. 45. H.Fritz-Niggli. 100-year of radiobiology: implication for biomedicine and future perspectives. Experietia, 14, 51(17), 652-664, 1995. 46. Birkenhake S., Sauer R. Historical essentials influencing the development of radiobiology in past 100 years. Experietia, 14, 51(17), 681-685, 1995.
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