Journal of Trace Elements in Medicine and Biology 25S (2011) S3S10

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Journal of Trace Elements in Medicine and Biology

journal homepage: www.elsevier.de/jtemb

FOURTH INTERNATIONAL FESTEM SYMPOSIUM

Bioelementology as an interdisciplinary integrative approach in life sciences: Terminology, classication, perspectives

Anatoly V. Skalny a,b,
a b

Institute of Bioelementology, Orenburg State University, Pobedy Avenue 13, Orenburg 460352, Russia Federal State Scientic Institution Institute of Toxicology, Federal Medico-Biological Agency of Russia, Bekhtereva str. 1, St. Petersburg 192019, Russia

a r t i c l e

i n f o

a b s t r a c t
The article presents the proposed concept of bioelements and the basic postulates of bioelementology for assessing and discussing them in the scientic community. It is known that chemical elements exist in the organism not by themselves, but in certain species having close interaction with other components. Such units are proposed to be called bioelements: the elementary functioning units of living matter, which are biologically active complexes of chemical elements as atoms, ions or nanoparticles with organic compounds of exogenous or biogenous origin. The scientic discipline that studies bioelements, is proposed to be called bioelementology. This discipline could lay the foundation for the integration of bioorganic chemistry, bioinorganic chemistry, biophysics, molecular biology and other parts of life sciences. 2010 Elsevier GmbH. All rights reserved.

Article history: Received 18 September 2010 Accepted 26 October 2010 Keywords: Bioelement Bioelementology Life science Integrative concept

Introduction Despite evident expectations that a great deal of future outstanding discoveries will be made in the interdisciplinary areas of science, there are still language barriers between the historically separate spheres of chemistry, biology, medicine and physics. Thus, it is one of the aims . . . to catalyse mutual understanding. (Metal Ions in Life Sciences, 2010) At present, scientic and educational literature on traditional bioinorganic chemistry is rather good and extensively describes the elementary structure, physical properties and functions of isolated biological molecules such as proteins and enzymes, containing or interacting with one or several chemical elements [13]. However, there is much less information about the functional signicance of chemical elements in living organisms in the ways in which these elements participate in the processes of life, i.e., in vivo, as well as about the meaning and signicance of selection of the elements (and their isotopes), the processes of absorption (binding), transport and nal localization in cells, the regulation of these processes and control of their interactions in a complex set of the holistic system [4]. The biological role of chemical elements has experienced intensive studying in the second half of the twentieth century. There was expressed the essentiality of about 20 chemical elements to liv-

ing organisms, deepened the knowledge of toxic and carcinogenic properties of a number of trace elements, created tens of thousands of drugs and dietary supplements containing trace elements, and food products fortied with them. But the lack of multidisciplinary approach has been the Achilles heel of biological trace element research [5]. However, we strongly believe that new developments in this direction are possible on the basis of synergetic achievements of bioorganic and bioinorganic chemistry, the disciplines which have played a distinct positive role in modern biological chemistry and, at the same time, to some extent a negative one due to the articial division of the unied science, investigating the biological role of all the chemical elements from organogens (O, H, N, C) to ultratrace elements, as well as proteomics, genomics, transcriptomics, metallomics and other omics, rapidly developing in recent decades. The desire to integrate the organic and inorganic approach in studying the biological role of chemical elements is observed in a number of fundamental works [6,7]. We [811] put forward and develop the concept of bioelements and bioelementology as an integrative scientic direction. This article is dedicated to the presentation of our concept of bioelements and the basic postulates of bioelementology for assessing and discussing them in the scientic community. The basic terms, the idea and classication of bioelementology are presented below. Bioelements: proposed basic terminology and classication

Corresponding author. E-mail address: skalny3@microelements.ru 0946-672X/$ see front matter 2010 Elsevier GmbH. All rights reserved. doi:10.1016/j.jtemb.2010.10.005

Well, the main term of bioelementology is bioelement. In literature we found the term bioelement. Different authors are using

S4 Table 1 Classication of bioelements. Primary Simple

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C, H, N, O, P, S, Si, Ca (structural) K, Na, Ca, Cl, Mg (electrolytic) Mg, Fe, Zn, Cu, Mn, Co, Cr, Mo, Sea , Sna , Fa , Ia , Nia , Va , Bb (enzymatic) H2 O, O2 , N2 , etc. Nucleic acids (deoxyadenosine, deoxycytidine, deoxyguanosine, deoxythymidine, adenosine, cytidine, guanosine, uridine) Glycans (fucose, galactose, glucose, glucuronic acid, mannose, N-acetylgalactosamine, N-acetylglucosamine, neuraminic acid, xylose, nononic acid, octulosonic acid, arabinose, arabinofuranose, colitose, fructose, galactofuranose, galacturonic acid, glucolactilic acid, heptose, legionaminic acid, mannuronic acid, N-acetylfucosamine, N-acetylgalacturonic acid, N-acetylmannosamine, N-acetylmannosaminuronic acid, N-acetylmuramic acid, N-acetylperosamine, N-acetylquinovosamine, perosamine, pseudaminic acid, rhamnose, talose) Proteins (alanine, arginine, aspartic acid, asparagine, cysteine, glutamic acid, glutamine, glycine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine, valine) Lipids (fatty acyls, glycerolipids, glycerophospholipids, polyketides, prenol lipids, saccharolipids, sphingolipids, sterol lipids) Metabolome (components) Metallome Lipidome Proteome Genome Transcriptome (. . .?)

Complicated

Secondary

Complicated (components of bioelemental systems, omes)

Note: Structural, electrolytic and enzymatic bioelements are separated according to Sansoni and Iyengar [17]. a Essential only for animals. b Essential only for plants.

it mainly as a synonym to chemical element which plays some biological role or exists in the living body. Why did we name elements chemical but not physical only following tradition, because chemistry as science formed much earlier than nuclear physics and physics of elementary particles? The elements have chemical and even more physical properties, but it is nonsense to separate special biological elements. The active use of the term bioelement by me and my followers in recent years in scientic articles [9,11], books [10,12,13], textbooks [14,15], and reports at international scientic meetings showed that part of the scientists, especially chemists, feel a certain rejection of it because of the association with the term chemical element. Nevertheless, it is difcult to nd another term which would be more apt and apparently satisfying for most scientists. In fact, element is a multivocal word. We comfortably use expressions electrical element, heating element, or data element. So, bioelement can be a similar case. It is known that the chemical element exists in the organism not by itself, but in close interaction with other components. There are no any particular elements in the cell that are solely typical of living nature. On the atom level there are no differences between the chemical composition of organic and inorganic matter. The differences are found on the higher, molecular level of organization. Thus, the position and classication of the chemical elements in the Periodic System of Elements (PSE) does not permit any statement to be made about their functional essentiality or their acute or chronic toxicity for living organisms. This is due to the fact that the Periodic System is based on purely physicochemical aspects [16]. Therefore B. Markert developed an idea about a Biological System of Elements (BSE), which primarily considers aspects of basic biochemical and physiological research. As the author said, Biological

processes on the molecular level are frequently based on physical and chemical conditions. . .. However, these physical and chemical regularities are frequently modied in biological systems. The BSE of B. Markert is obtained from data on correlation analysis, physiological function of individual elements in the living organism, evolutional development out of the inorganic environment and with respect to their uptake by the living organism as a neutral molecule or charged ion. Atoms, atomic nuclei, elementary particles and elds that bind them, which have independent signicance at the physicochemical stage of evolution, after being included in biological molecules lose this self-importance and play their role in the ensemble that I call bioelement, where everything is interdependent, more complicated and at the same time more vulnerable to external inuence. Since the general conditions of biological evolution (the composition of biosphere), are continuously changing, a set of bioelements in a living organism can also change. This distinguishes them from chemical elements as objects of physicochemical stage, which remain identical to themselves along the course of evolution. So, bioelement is the elemental functioning unit of living matter, which is a biologically active complex of chemical elements as atoms, ions and nanoparticles with organic compounds of exogenous (primary) or biogenous (secondary) origin (this is Postulate 1). It should be noted that our views on the denition of bioelements in recent years also underwent a considerable evolution [811]. Initially, me and my colleague professor Rudakov imagine bioelements as chemical elements which constantly occur in the body, are necessary for its functioning and exhibiting biological properties (i.e., new, non-chemical and physical properties, such as the bodys need for the element, the toxicity of the element for the body, synergism and antagonism within the organism)

A.V. Skalny / Journal of Trace Elements in Medicine and Biology 25S (2011) S3S10 Table 2 The fundamental main characteristics of chemical elements and bioelements. Chemical element There in the biosphere and beyond. Weight is virtually unlimited. No quantitative limits. Bioelement There mainly in biosphere. Outside biosphere, existence is temporary or impossible. Weight limited.

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The quantitative limit exists (depends on the space of the biosphere), as space available for organisms is limited. Limit of bioelements in the mass of life is constant in the course of geological time. Exists in millions of biological compounds. Like a living organism can be born only by another living organism, the new bioelement appears in biochemical transformations of the previous compounds (living objects, containing bioelements). In the course of geological time, some qualitative changes in forms of bioelements happen, which lead to the evolution of species or loss of some of them. Bioelements are formed not only during natural biochemical transformations of other living bodies, containing bioelements, but can also be created as a result of human activities (industrial synthesis of bioelements, biotech processes) from abiotic substances or other bioelements (from simple to complicated). Formation of bioelement (i.e., form of existence of a chemical element in the biosphere), as well as the creation of a natural living body, is process irreversible in time. Number of bioelements and number of living natural bodies are limited by the size of the biosphere (Earth).

Exists in 20003000 species of minerals and corresponding chemical compounds. Involved in formation of biologically inert natural objects by physico-chemical and geological processes, regardless of the previously existed natural objects.

Its formation may occur in living bodies, varying in its manifestations and giving inert natural bodies elements incorporated in living natural body (e.g., concretions in kidneys).

The process of turning abioelements into inorganic matter, as the processes that created the inert natural object, is reversible in time. Number of elements as components of inert natural objects does not depend on size of the planet, but is determined by the properties of planetary matter by energy. Modied from ideas of V.I. Vernadsky, 2002 about abiotic and biotic matter.

[11]. At that moment we determined bioelementology as scientic and practical direction, studying the composition, content, relations and interaction of chemical elements and their compounds in living systems. At the same time among bioelements we initially attributed only organogens, macroelements and essential trace elements. However, the deepening into this problem demonstrated the insufciency of such ideas. Later [9] I based the denition and subdivision of bioelements on two columns: the rst is the classication of chemical elements proposed by Sansoni and Iyengar [17], who, in my opinion, quite correctly in terms of biological functions divided the chemical elements into structural, electrolytic and enzymatic (see Markert [16]). The second is the notion of building blocks of life by Marth [18], with the necessary additions from my point of view, namely the separation of the group critically vital simple molecules such as H2 O, O2 , H2 , N2 , etc. At the same time, some omes are systems (or ensembles) of closely related bioelements. Since the synthesis of secondary bioelements became possible for the rst time only in the protocell, we have attributed genome (DNA) and transcriptome (RNA) to the secondary (complicated) bioelements. The generalized classication of bioelements is presented in Table 1. In principle, bioelements include any chemical structures found in living nature but do not possess a set of fundamental properties of living things themselves: metabolism, variability, reproduction and heredity. Primarily, these are organogens (C, H, N, O), P, S and representatives of four classes of small organic molecules which compose the cells: amino acids, nucleotides, sugars, fatty acids, and coordination structures, aquated ions of vital macro and trace elements and water as well. Bioelement is not a chemical element inside a molecular compound, but it is a temporarily formed biocomplex, whereas the chemical element is bound by a covalent (chelate) bond to the organic molecule. They should not be considered separately, because, interacting, together they produce biological effect of new quality [19]. If a chemical element is a physicochemical unit of the matters evolution, then a bioelement is a precursor of a biological

unit, which has physicochemical nature. Fundamental differences between chemical elements and their compounds in abiogenic media and bioelements are described in Table 2. Bioelements can continuously form from ionic compounds when entering the cell. Inside the cell, biopolymers and their complexes create a complicated, coordinated and regulated system for the transformation of substances. The cell is the main place of natural birth of secondary bioelements and their destruction. According to modern views, life processes cannot occur outside the cell. Therefore, the cell is considered the smallest quantum of life, which, for managing its internal parameters and performing cellcell interactions, use information, energy and substances, including bioelements they obtain from the environment. Bioelement is yet a substance. A cell (organism) is already a being. In our opinion (Fig. 1), bioelements are precursors of living matter, a successful combination of which, particularly of polymerion reactions running autocatalytically, led to the formation of cells (this is Postulate 2). We propose to call the assembly of bioelements bioelementome unlike elementome as an assembly of chemical elements and their compounds. Bioelementome is a particular continuum of molecules for the maintenance of biological units of evolution, possessing the ability to control the process, and biological objects (this is Postulate 3). However, when considering the biological role of bioelements, we should clearly distinguish two questions. The rst is a question of initial formation and participation of bioelements in the origin of life. The second is a question concerning the role of bioelements in the modern biosphere, at the anthropogenic stage of its development. i.e., one should separate the role of bioelements during the early formation of the biosphere, and the modern role of bioelements. While before and during the early formation of the biosphere bioelements formed by the exchange synthesis or came from the outside universe, now an increasingly signicant role is passing to biogenous synthesis of bioelements by living organisms. According to modern ideas, the origin of life on Earth was initiated from simple physicalchemical substances and phenomena,

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Fig. 1. Structural levels of the matter. By Yu.N. Orlov [20], expanded by A.V. Skalny).

whose participants are always atoms of the ve major components of biological molecules (C, H, N, O, P) and a set of other chemical elements. Over billions of years, the atoms connecting with each other under certain conditions (climate, water availability, etc.) by different types of bonds (ionic, covalent, metallic, molecular, hydrogen, etc.) produced the most stable compounds capable of copying themselves. Currently in the scientic literature a number of hypotheses of life origin are presented [7,2125]. All these ideas are in their infancy, and none of the hypotheses are transformed even in theory [26]. But, from our point of view, one thing is clear: the origin of life is based on the formation of its precursors which themselves are necessary but not sufcient conditions for the emergence of life as a biological phenomenon. These particular quasi-living or preliving molecules we propose to call bioelements (primary ones) (this is Postulate 4). Primary bioelements once produced the rst protocell LUCA [24] or probiont [27] a hypothetical primary organism which originated all the modern diversity of life on Earth, contained, inter alia, the macromolecules (pro-proteins and pro-DNA) and acquired the ability to reproduce itself [27]. Primary bioelements existed long before the emergence of life; they had the highest resistance to external conditions due to its simplicity. Some of the bioelements became components of active centres in enzymes, dramatically accelerating the evolution of life due to the formation of metabolic pathways. Bioelements are components and legacy of the primordial soup, from separate ions to H2 O, CO2 , O2 , glucose and other sugars, amino acids and proto-RNA. Electric discharges, electromagnetic elds, ultraviolet and visible light, gases these are the conditions (environment) in which bioelements can unite and turn into the living. We call these simple bioelements the rst-order bioelements or organogens that produce under certain conditions the rst organic molecule (DNA, RNA, ATP?) [7,27]. These bioelements together with Ca constitute 99% of the human body mass. It is believed

that only certain non-metals C, N, O, S and Se are able to create stable polymeric structures in normal conditions of contemporary environment [4]. These non-metals form strong bonds with carbon, and therefore are able to encode information in the form of certain sequences of atoms and functional groups. They can easily share electrons of the outer shell to atoms of elements not only from the mentioned list, but also from other groups of the Mendeleevs Periodic System, including metals, forming compounds with ionic, covalent or donoracceptor bonds. These elements form functional groups of bioligands, forming coordination compounds with metals. These functional groups can rather easily form coordination compounds with metals mainly of the III and IV periods of Periodic System: Na, K, Mg, Ca, V, Cr, Fe, Co, Ni, Cu, Zn and Mo the elements of the V period as an exception. Only these chemical elements have mostly the same size as atoms, as non-metals, and have no obvious steric constraints toward the formation of coordination compounds [3]. The above-mentioned chemical elements of the III and IV periods of the Periodic System play different biological roles [12]. Alkali metals K, Na play a dominant role in maintaining electrolyte homeostasis, in providing functions of messengers. Transition metals in accordance with their abundance and characteristics of the electron shells take part in active centres of energy exchange enzymes and in cyclic redox reactions [3]. Thus, the course of chemical evolution has selected the key molecules which provided emergence and existence of primary organisms: these are nitrogenous bases and nucleic acids, amino acids, peptides, proteins, mono, oligo and polysaccharides, carotenoids, fatty acids, porphyrin structure and, the main thing from our point of view, complexes of these molecules with transition metals. The complexation provided a transfer of electrons and protons in enzymatic systems. It solved the problem of energy for organic life. About 4 billion years ago the rst living cells were formed and biochemical homogeneity of living beings was achieved. The cells

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contained a matrix system, a set of catalysts surrounded by a membrane, and used organic molecules from the environment as the sources of energy and carbon. The biological stage of evolution has come. Thus, as a result of chemical evolution on the Earth there appeared the pre-biological organic world [28], a variety of living systems, which consists of the same set of molecules (bioelements), work by the same laws, have the metabolism based on the same principles, and the system of homeostasis that can control the ows of food, energy and information. . . . the part of history preceding the emergence of the simplest organism is under a tight veil of secrecy. Physics, as well as molecular biology and biochemistry are powerless to overcome the conict between their basic laws and the need to simultaneously have both an enzyme that controls the synthesis of informational molecules (DNA or RNA) and these molecules themselves to encode the synthesis of the enzyme that controls their synthesis [28]. The biological evolution has led to a sharp increase in mass and diversity of the living substance on the planet, including formation of new chemical compounds and molecules, the novel (secondary) bioelements (in cells) (this is Postulate 5). The biosphere appeared as an open thermodynamic system in which some secondary bioelements can disappear and others can appear, while the set of primary bioelements progenitors of life is likely to remain mainly stable. Simple bioelements produced four fundamental components of cellular life, which, according to Marth [18], are divided into 68 molecular building blocks (building blocks of life), i.e., the simplest bioelements formed more complicated, macromolecular bioelements. Following this logic, we propose to subdivide bioelements into simple (atoms, ions and water as the universal solvent), and complicated ones, consisting of the above-mentioned 68 molecules (8 of them are nucleosides, which compose DNA and RNA, 20 are natural amino acids necessary for protein synthesis, at least 32 glycans, 8 types of lipids, see Table 1) [18] (this is Postulate 6). The above-mentioned (a) simplest (H, C, O, N, P, S, vital chemical elements, evolutionarily selected by cells from the environment to supply biological functions) and (b) derivative (the 68 molecules, water, oxygen, etc.) bioelements we propose to call primary bioelements, respectively, simple (a) and complicated (b). Primary bioelements are, in essence, pre-biological elements or prebiotic [29]. Other bioelements are likely secondary, because for their formation the primary bioelements were selected by cells from the extracellular environment in the process of evolution for performing specic regulatory functions (this is Postulate 7). It is very important for understanding the biological role of chemical elements, which is determined not so much by a chemical element as such, as by its chemical species in the body. i.e., the talk about a specic role of a chemical element in living organism has no biological meaning. The biological meaning is in its chemical variety. For example, during photosynthesis there formed bioelements: organic compounds, and oxygen. Bioelements provide not only building material for the living matter, but also the energy to maintain body functions. The content of chemical elements such as C, N, O, H, S, P (in simple and complex molecules) in a living organism is the most stable, since they are part of its basis, the matrix of the living matter or organism. In turn, the content of trace elements and especially ultratrace elements in living organisms is highly dependent on living conditions, nutrition, and the state of the organism. Thus, bioelements can be subdivided into primary, i.e., those which could exist before the origin of life, and secondary ones, i.e., those which have formed as producers of living organisms.

This division is necessary for us to better understand the nature and role of bioelements. For example, the fact that life is a selfsustaining process that can produce raw material for new living structures. This agrees with the theory of natural self-organization of pre-biological processes by Eigen [30] and ideas of Prigogine [31] about self-organization in open systems. Based on the ideas of Kaznacheev [32], we can consider bioelements the internal condition (medium) for the existence of biological systems, whereas electromagnetic components can be considered the external condition (environment). Biosphere is an assembly of bioelements and living organisms existing under permanent regulatory inuence of physico-chemical factors of terrestrial and cosmic origin. Let us consider the creation of a secondary bioelement from metals (as adapted from Kriss et al. [33]). Bioelements: a) aqua-ions of alkali metals; b) aqua-ions and relatively unstable complexes with different ligands of alkaline earth metals; c) complexes (of different strength) of transition metal ions with relatively simple ligands (amino acids, carbohydrates, carboxylic acids, etc.) that form membrane-transport forms of metals. The creation of membrane transport forms of metals in the digestive tract is the rst stage of the formation of secondary bioelements the extracellular stage (where low molecular weight metalligand complexes and aqua-ions precursors of true bioelements are formed). Metal ions or their simple complexes, passed through the membrane, remain inside the cell or (transition metal ions) interact with transferrins high-molecular transport proteins.This is the stage II (intracellular). Metal ion in the form of aqua-ion, low-molecular or metalbound transferrin, reacts with a protein, nucleotide or nucleic acid, and being included in this metal complex, performs its basic (biological) function. Most often, metal ions interact with apoenzyme, forming metalloenzymes, or activate enzymes without being a part of their active centres. Metal ions with proteins may form metalloproteins for other functions. Thus, the function of kalmodulin changes when it forms a complex with calcium. Iron ion in haem, binding to the globin, turns the latter into myoglobin or haemoglobin.This is the stage III. With time, metalloproteins become decomposed, remnants of the proteins are eliminated from the organism, and metal ions are either also eliminated, or included again in the metabolic chain. This is the stage IV of the bioelement formation. Bioelemental analysis is the analysis of bioelements in living systems and their environment, in contrast to elemental analysis, which is an analysis of chemical elements in all media including biological uids and tissues (this is Postulate 8). Bioelementology as an integrative science We believe that the developing concept of bioelements lays the foundation for the integration of bioorganic chemistry, bioinorganic chemistry, biophysics, molecular biology and other parts of life sciences (Fig. 2), for reasons of their hierarchical structurization, subdividing them (after the integration) into the pre-biology and biology. The personal experience of existence and development of the Chair of Nutritiology and Bioelementology, the Institute of Bioelementology, founded by the author in 2003 at Orenburg State University, the debates at the International symposium Bioelements and on the pages of thematic supplements Bioelementologiya to the journal Vestnik of Orenburg State University,

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Fig. 2. The bioelementology, an integrative scheme.

as well as the discussion at II RUSTEM Congress (Tver, 2008) and IV FESTEM Symposium (St. Petersburg, 2010) have convinced us of the timeliness and advisability of bioelementology. However, we are aware of the necessity to discuss new terms introducing into scientic use or modications of already known terms. In recent years, along with the evolution of our knowledge and understanding of bioelements, the denitions of bioelementology evolved [911]. Here we try to dene bioelementology from our current point of view: Bioelementology is a science, which can unite all the omics, probably including genomics. It would be great to call such unifying discipline biomics, however this term already exists. Authors of the term genomics, McKusick and Riddle, in the editorial article to the rst issue of the journal Genomics have explained the introduction of the new term as follows: . . .logies are very academic, while . . .omics are more aggressive and democratic [34] in style of live matter studying. I am pleased to note that since 2010 in Russia the Institute of Biochemical Genetics, Ural Scientic Center, Russian Academy of Sciences has issued the electronic journal Biomics [http://ibg.anrb.ru/biomics.html]. The founders of this issue consider biomics as a synonym of modern biology. According to the editorial board, once it happens that part of the root, sufx and the ending omics have become an integral part of a series of new biological disciplines, this part of the root, sufx and the ending may unite a whole group of biological sciences which apply methods of

physicochemical biology in their researches. Although the authors did not aim to introduce a new scientic term biomics, they actually, and concurrently with my own publication [9], came to the opinion about the appropriateness and timeliness of integration of the omics. Also, from Wikipedia we know, that biomics is the biological study of biomes, and the processing of data, such as ecological communities of plants, animals and soil organisms. Traditionally, biomics is a part of biogeography, ecosystems and habitats research. In molecular biology, biomics uses bioinformatics approaches to collectively analyze diverse biome data. A biome may contain very large scale omics information, such as metagenome and pangenome where genomic sequences are mass produced. So, bioelementology could be called biomics sensu lato. It seems to me that the idea of BSE is very interesting, but from the standpoint of bioelementology is not very productive, as it covers an important, but only preliminary part of the problem, isolating chemical elements in living systems from other members of biological processes. There is no visible bridge between elementary (simple) and more complex components of the pre-life. Thus, bioelementology is a part of biology (and of the life science in terms of Vernadsky), a science about the biological role of substances, important for building and existence of the living matter (this is Postulate 9). Bioelementology is a direction of fundamental science studying the transition state of the matter (evolution from biologically inert

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to living), formation and change of bioelements, which are vital or conditionally essential for the living matter, under the inuence of various physical interactions and the matrix effect of water. The term bioelementology was rst used in the scientic literature by Bikkulova and Ishmuratova in 1999 [35]. The subject of bioelementology, however, was considered by the authors as a study of biologically active simple, complex and coordinated compounds of chemical elements (metals and non-metals except f-elements of the Periodic System), and the inuence of their deciency or excess on human organism and biosphere. As it was stated above, we conceive of the genius Russian scientist Vladimir Vernadsky as the forerunner of bioelementology. Bioelementology as an integrative science, based on the ideas of Vernadsky, will bring us closer to understanding the origin of life. Unlike the currently prevailing molecular approach, which unfortunately does not solve the problem of the life origin despite the involvement in consideration of new biochemical factors nucleic acids, matrix mechanisms of continuity and biochemical memory [32], bioelementology, in our view, will help to consider the conditions of life more holistically as the presence of bioelements is already the most important condition for its maintenance. Both the planetary environment, which surrounds the living substance, and the extraplanetary space environment which is inuencing it provide the necessary material and energy ows for the proper functioning and continual renewal of the structure of living matter. The ideas of autotrophy of the mankind and noosphere, suggested by Vernadsky in 1923 [19], have fostered the epoch of nanobiology, the living matter of Universe. We believe that bioelementology can help to solve the main problem of mankind achievement of autotrophy through answering the question for the essence of the living matter of Earth and the identication of this essence with a wider principle of life existence in the Universe [36]. The bioelementology combines the systemic and integrative approaches in life science and is a possible precursor to systemic biology.

Conclusion The materials above illustrate that the evolution of living organisms on Earth was accompanied by a broadening and deepening of the utilization of chemical elements and their compounds, i.e., in fact, by diversication, improvement and complication of bioelements. This process continues today in both natural and articial environment, if allowing for the development of biotechnology, genetic engineering and pharmacy. Diversication of bioelements is a natural tool of the evolution aimed at the adaptation of living organisms to the changing conditions of their existence. The emergence of new bioelements accompanies the process of evolution from simple prokaryotic cells (universal) to specialized cells within multicellular organisms with longer duration of individual life at a deceleration of reproduction rate. Changing the composition of the extracellular environment, such as the concentration of key ions or gases, it is possible to cause a cascade of formation of new bioelements. A more diverse set of bioelements is observed in organisms with relatively low reproduction rates, but with a longer individual life. Bioelements existed yet before the emergence of life. The life itself (since the formation of the cell) became a powerful and very efcient producer and consumer of new bioelements. The change from anaerobic to aerobic life was accompanied by a widening of the spectrum (variety) of bioelements. Therefore an evolutionary or revolutionary (with the help of new technologies) creation of new forms of cells and hence of new life is possible that can open to mankind unprecedented prospects for development, as well as

new threats to its existence if the process of the formation of new life forms will be uncontrolled or inadequately controlled. It must be remembered that a set of bioelements is a necessary but not sufcient condition for the formation of life. In many cases in medicine, in our opinion, it is possible to use bioelements for maintaining organs and tissues instead of using cell cultures and tissues, because it is not always necessary or possible (including for nancial reasons) to recover the function by a substance, organ or tissue, completely identical to the living one (e.g., in transplantology, orthopedics, in treatment of osteoporosis, diseases of skin, and hair.). The development of bioelementology may lead to the appearance of modied cells or technologies for the creation of new cells which can be used for medical purposes. Without going into detail, we only note that this tale may sooner become reality with the correct formulation of tasks, based on the correct understanding of the hierarchy of pre-living processes and of life itself, on the formation of new methodological approaches on its basis, on the proper division of essential substances in necessary and sufcient, primary and secondary, with a better understanding of the boundary between pre-living and living, between the set of bioelements and life. Thus, which further steps can result from appearance and establishment of the new term and new integrative scientic direction? Change in educational programs for high school students of biological, chemical and physical specialties, creation of special programs for biotechnologists, medical researchers, ecologists and pharmacists. And this will demand united efforts of scientists and specialists from adjacent elds. Integration of scientic researches without division into separate parts, studied by only one of the omics, though this will demand deeper and more global planning of scientic investigations on the basis of the multidisciplinary concept. One should start from the fact that, like multielement analysis in biology and medicine, the study of the limited number of parameters (one omics) will lead to further accumulation of intermediate scientic investigations, which really solve not one question of modern biology. The ranking of studies on biological systems (bioelementology, biology of plants, vertebrates, humans, etc.) will allow to scan the living matter from the physico-chemical stage of its evolution to the highest social stage (noosphere) in a relatively short historical period. Acknowledgement I would like to thank my colleague Dr. Andrei Grabeklis for his valuable help and advice. References
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