The Riddle of "Life," A Biologist's Critical View

Naturwissenschaften (2009) 96:123 DOI 10.
1007/s00114-008-0422-8
REVIEW
The riddle of life, a biologists critical view

Heinz Penzlin
Received: 5 March 2007 / Revised: 17 June 2008 / Accepted: 24 June 2008 / Published online: 2 September 2008 # Springer-Verlag 2008
Abstract To approach the question of what life is, we first have to state that life exists exclusively as the being-alive of discrete spatio-temporal entities. The simplest unit that can legitimately be considered to be alive is an intact prokaryotic cell as a whole. In this review, I discuss critically various aspects of the nature and singularity of living beings from the biologists point of view. In spite of the enormous richness of forms and performances in the biotic realm, there is a considerable uniformity in the chemical machinery of life, which powers all organisms. Life represents a dynamic state; it is performance of a system of singular kind: life-as-action approach. All lifeas-things hypotheses are wrong from the beginning. Life is conditioned by certain substances but not defined by them. Living systems are endowed with a power to maintain their inherent functional order (organization) permanently against disruptive influences. The term organization inherently involves the aspect of functionality, the teleonomic, purposeful cooperation of structural and functional elements. Structures in turn require information for their specification, and information presupposes a source. This source is constituted in living systems by the nucleic acids. Organisms are unique in having a capacity to use, maintain, and replicate internal information, which yields the basis for their specific organization in its perpetuation. The
existence of a genome is a necessary condition for life and one of the absolute differences between living and non-living matter. Organization includes both what makes life possible and what is determined by it. It is not something implanted into the living beings but has its origin and capacity for maintenance within the system itself. It is the essence of life. The property of being alive we can consider as an emergent property of cells that corresponds to a certain level of selfmaintained complex order or organization. Keywords Living state . Vital organization . Metabolism . Self-maintenance . Autonomy . Emergence
Introduction The bondage of biology to the physical sciences has lasted more than half a century. It is now time for biology to take her right full place as an exact independent science: to speak her own language and not that of other sciences. Haldane (1922) Living matter exists in a wondrous array of emergent products, perhaps 10 to 20 million different species or even morenobody really knows the exact number. Life is so ubiquitous in our world, so evident that we fail to even wonder at its existence. We take it for granted that a human being composed of an estimated 10 billion (1013!) tissue cells of about 350 different types and another 30 billion blood cells should develop from a relatively unstructured seminated egg celland this, fortunately, with a remarkably low rate of error. And nevertheless, embryogenesis doubtlessly belongs to the most amazing and puzzling phenomena to be found in our natural world. What causes all the cells to differentiate in the way that they do so a
H. Penzlin Institut fr Allgemeine Zoologie und Tierphysiologie Friedrich-Schiller-Universitt Jena, Erbertstrasse 1, 07745 Jena, Germany H. Penzlin (*) Leo-Sachse-Strasse 10, 07749 Jena, Germany e-mail: penzlin-jena@t-online.de
Naturwissenschaften (2009) 96:123
healthy child with a head, trunk, arms, and legs, with a brain, heart, and all the other organs comes into being and begins to speak and to think? There is probably no one who better recognizes how remarkable life actually is than the developmental biologist. Two hundred years ago, Treviranus, Lamarck, and others introduced the term biology to describe the science dealing with living beings. In the light of the multiple and heterogeneous questions it asks and approaches it takes, the term life sciences is more usual nowadays. Strictly speaking, despite generations of trying, the subject matter of life sciences is as yet still undefined. My central intention in this review therefore is not to try to define life, which is probably a hopeless undertaking, but to attempt to work out what living entities are and to demonstrate that living beings are distinct from non-living entities not only in their degree of complexity but fundamentally, in principle. Organisms have properties and facilities, which are unique to them and only to them.
exists as a single, unique, spatiotemporally restricted entity with a beginning and an end. Under present conditions on Earth, no organism comes into being spontaneously out of non-living matter. In every case, living entities derive from living entities: omne vivum e vivo (Lorenz Oken). Each organism has a unique, non-repeatable history. Because organisms derive from other organisms (ancestors) and produce yet other organisms (descendents), a continuous succession of generations connects each present organism with lifes origin on earth. Cells as elementary organisms Despite the tremendous diversity of living forms in our world, scientists in nineteenth century discovered that all present-day living organisms are made up of one, some, thousands, millions, or billions of cells. The entire metabolism takes place in cells, and all cells are derived from the division into two of previously existing cells: Omnis cellula e cellula (Rudolf Virchow). Life is cell activityits uniqueness is the uniqueness of the cell. There are only two different types of cells (Fig. 1), the primitive prokaryotic cell (protocyte) of the archaea and bacteria and the essentially more complex eukaryotic cell (eucyte) of all the other organisms (protista, fungi, plants, and animals). The latter is about a thousand-fold more voluminous and more complex than the protocyte. No intermediate forms exist between these two types of cells that would guide a gradual evolutionary inference between the prokaryotic and eukaryotic state. The protocyte has no membrane-bounded organelles. Its genome consists in the minimum case of a single, double-stranded, closed loop of DNA. In contrast, the eucyte contains organelles surrounded by double membranes, a nucleus with its contiguous endoplasmatic reticulum, a Golgi apparatus, and flagella with a 9-+2-pattern of microtubule arrangement. During the interphase, their hereditary material is concentrated in a set of complex chromosomes inside the cell nucleus. The whole cell is the most elementary unit that can maintain life; it is the least complex thing that properly lives. When protozoan cells divide into two halves, one containing the nucleus and the other without, only the first can maintain life. A nucleus-less Amoeba is still able to eat and digest for some time. Later on, this capacity disappears, and the protozoan rejects the undigested food. Only cell fragments with an intact nucleus are able to regenerate the lost parts. The physiologist Ernst von Brcke characterized the cell as an elementary organism (Brcke 1851), and many influential biologists (Walter Flemming 1882, E. B. Wilson 1907, Frederick Gowland Hopkins 1913, and others) agree with him that life should be considered as the activityor ensemble of activitiesof whole cells and nothing less. This conclusion expresses on the cellular level
Life means being-alive of discrete entities: organisms Life exists exclusively as the being-alive of something To approach to the question of what life is, we first have to state that life exists exclusively as the being-alive of discrete entities, which we call living creatures or organisms. No life exists outside and independently of organisms; no independent agent makes inorganic matter alive. Life always means being alive. There is no entity life, which we can make the object of our science. Therefore, biology is not the science of life but the science of living entities in all their forms, aspects, and hierarchical levels. We can consider the living entities as highly complex systems and life as the specific performance of these systems. This underlines the absolute necessity of systems thinking in General Biology. The negation of a vital agent independent from organisms is not a trivial step by any means. It implicates a fundamental point of view in the discussion of the problem of life. Many cultural groups, philosophies, and religions, for example, believed and believe in a vital agent, which also exists and acts outside of and independently from organisms. For Plato for instance, as already mentioned, the soul is a distinct non-material entity, which bonds to certain objects and induces in them animate behavior. However, daily experience teaches us that such a duality does not exist. Life existsas already mentioned only as being-alive of highly complex, dynamic systems with the fundamental property to autonomously maintain and replicate their internal organization. Each organism
Naturwissenschaften (2009) 96:123 Fig. 1 Diagrams of the larger and more complicated eukaryotic (animal) cell (left) and the simpler prokaryotic cell (right). Only the eukaryotic cells have a separate compartment (nucleus) that contains their DNA (left figure after Storch and Welsch 2005, right figure after Kaplan 1972)
Eukaryotic cell
Prokaryotic cell
the holistic concept once formulated by Kant for the organism as a whole. Below the cellular level, no independent life is possible. Although some organelles, such as mitochondria and chloroplasts, undergo replication, this requires the functioning of the integrated cell. In trying to define the essence of the living state (not of organisms!) fundamental for all living entities, we may confine ourselves to considering life at its cellular level. When the first multicellular organisms appeared, life had already existed approximately 2.8 Ga. About three quarters of evolution up to now has taken place on a cellular level or, in other words, was cell evolution1. Viruses are the most abundant biological entities on our planet (Breitbart and Rohwer 2005). There are 10311032 virus particles in the biosphere; this is at least one order of magnitude more than the number of host cells! Virus particles (virions) indeed contain genetic information (DNA or RNA), but they are incapable of growth or division by themselves. They lack the machinery to generate energy or to synthesize their own proteins. They are obligate parasites and depend on the host cells ribosomes to synthesize their
own proteins. Therefore, extant viruses are not truly alive. They were generally considered to be fragments of living entities that have lost their capacity for autonomous existence, but we must own up to the fact that we really have no sound knowledge of how the entire domain of viruses is organized, what the origins of viruses are, and how they evolve (Bamford et al. 2005). Recently, Koonin et al. (2006) proposed an alternative hypothesis to the scenarios that describe viruses originating as genes that have escaped from cellular organisms. In their concept of an ancient virus world, the principal lineages of viruses and related selfish agents emerged from a primordial pool of primitive genetic elements, the ancestors of both cellular and viral genes. In the opinion of these authors, the emergence of substantial genetic diversity antedates the advent of fully fledged cells. To explain the crucial step of compartmentalization in the primordial pool, a highly speculative model has been elaborated (Koonin and Martin 2005). The assumption of a non-cellular last universal common ancestor of the three domains Bacteria, Archaea, and Eukaryotes, as favoured in this scenario, remains a topic of controversial discussion (e.g. Gogarten and Taiz 1992). Last vital units below the cell level?life-as-things hypotheses The assumption that single substances are the primary vehicles of life has a long tradition beginning with the preSocratic philosophers. In the Middle Ages and early Renaissance, life was sometimes identified as a fluid substance known as liquor vitae. Felix Dujardins living jelly or sarcode was later succeeded by the more general term protoplasm which was considered by many as the
This cell-as-elementary-organism theorem is not inconsistent with the well-known fact that the totipotency of the zygote gets lost in the descendants of the zygote during the ontogenesis of a multicellular organism. The cells become determined and differentiate into specific types of cells. This differentiation usually results from the differential expression of genes in the cell, i.e., from the differential regulation of transcription, posttranscriptional events, or translation but not from a loss of DNA or irreversible changes in the genome. It is only irreversible in certain types of cells. In many cases, differentiation is reversible under the right environmental circumstances. Transdifferentiation of one differentiated cell type into another type has been shown to occur for instance during regeneration and in cells in tissue culture.
material basis of life until well into the twentieth century. In the second half of the nineteenth century under the influence of the blossoming discipline of organic chemistry, the notion of last units of life below the cellular level was widespread among theoretical biologists: physiological entities (Spencer), lebendiges Eiwei (Pflger 1875), Bioblasts (O. Hertwig 1906), Biophors (Weismann 1892), Protomers (Heidenhain 1894), or Biogens (Verworn 1903). All these life-as-things hypotheses base on the effort to explain the specific properties and performances of living systems in terms of mysterious units, molecules, or aggregates of molecules. Nowadays, it is clear that no single molecule, no single component of the cell per se is alive. Chemists have learned to synthesize any protein or any nucleotide sequence but, in doing so, have never created life. The birth of life on earth did not coincide with the first appearance of a certain protein molecule as the physicist Pascual Jordan believed. Neither is it true that life began with the appearance of the first nucleic acid strand in the primeval soup, which was able to replicate and to mutate and thus became the subject of selection, as Kuhn and Waser (1982) once stated. If that were the case, scientists would have succeeded in making artificial life in a test tube many times over. We have to accept that life is the performance of complex internally organized systems and as such necessarily began as a minimal integral multimolecular system. Translation and replication are consequences of the total functioning of the whole. The role and importance of DNA is frequently exaggerated. It is often uncritically elevated to the vital principle, the thread of life. What we must bear in mind, however, is that the DNA double helix can only fulfill its central function inside a living cell. Replication requires not just energy but also the presence of several protein enzymes and some complex precursors. The same is true of the transcription of information from DNA to RNA and of the translation of the RNA sequence into the proper sequence of amino acids in the polypeptide chain. Translation requires highly specific aminoacyl synthetases to attach the correct amino acid to the correct transfer RNA (tRNA), thus permitting the synthesis of polypeptide chains with the right amino acid sequence. This sequence determines at a given pH and temperature the threedimensional structure (tertiary structure) of the polypeptide chain, which is accountable for the function of this protein. No one molecule, including DNA, catalyses its own formation. There is no such thing as a genobiosis (Kaplan 1972) on the level of genes! Numerous efforts (Joyce and Orgel 1986; Joyce 1987) to find an enzyme-free polynucleotide system able to undergo replication cycles by sequentially and correctly adding the proper nucleotide to the newly synthesized strand have not yet succeeded (Kaufmann 1996).
Scientists who pretend that the riddle of life has been solved by modern molecular biology are quite simple deluded. Claims such as genes have created us body and mind; so when we know exactly what the genes look like, we will know what it is to be human, are absurd, as Lowentin (1992) pointed out in his readable polemic. Life cannot be associated with a single substance. All life-asthings views or positions are wrong from the beginning. Life is conditioned by certain substances but not defined by them. It is in no way a thing; on the contrary, it is action, it is dynamic, it is the performance of certain natural systems, which we call alive: life-as-action approach. Minimal cells Over the last few years, much theoretical and experimental work has been done to determine the minimum set of genes necessary and sufficient to maintain a functioning cell under ideal conditions, i.e., in the presence of unlimited amounts of all essential nutrients and in the absence of any adverse factors, including competition. Morowitz (1967) calculated that the minimal cell may be about one tenth smaller than Mycoplasma genitalium, the organism with the smallest known genome size. The wall-less Mycoplasma has a cell diameter of 250 nm. That means that, in the case of an intracellular pH value of 7.0, on average, only two protons can exist simultaneously in its plasma. M. genitalium and Buchnera sp. (Shimkets 1998) do not represent a type of ancestral cell but evolved from more conventional progenitors by a process of massive genome reduction in connection with their life style (Islas et al. 2004): M. genitalium is an obligate parasite in the human urogenital system and Buchnera sp. an endosymbiont. Their life styles permit the direct import of several metabolites and essential compounds from the host and, consequently, the withdrawal of some synthesis activities. It is probably not wrong to suppose that the largely unredundant genome of M. genitalium comes close to the minimal gene set essential for maintaining life. The genome of M. genitalium consists of one circular double strand of DNA and has 580,074 base pairs (580 kb). Out of 487 protein-coding genes, Glass et al. (2006) identified only 100 nonessential genes. The remaining 387 protein-coding genes plus three phosphate-transporting genes and 43 RNA-coding genes constitute the set of genes essential for the existence of this individual. Genes for electron transport and the citrate cycle are missing. Only one gene (enzyme) exists for the synthesis of amino acids. Gil et al. (2004), on the basis of their work with Buchnera sp. and other organisms, proposed a protein-coding gene core of just 206 for a minimal bacterial gene set (Table 1). Results obtained by other authors are close to those presented by Gil and his co-workers. Two hundred to 300 genes are
Naturwissenschaften (2009) 96:123 Table 1 Core of a minimal bacterial gene set basing on comparison of Buchnera sp. and other organism genomes (Gil et al. 2004) Function Number of genes In sum DNA metabolism Basic replication machinery DNA repair, restriction and modification RNA metabolism Basic transcription machinery Translation Aminoacyl-tRNA synthesis tRNA maturation and modification Ribosomal proteins Ribosome function, maturation and modification Translation factors RNA degradation Protein metabolism Post-translational modification Folding Translocation and secretion Turnover Cellular processes Energetic and intermediary metabolism Poorly characterized Total 16 13 3 106 8 21 6 50 7 12 2 15 2 5 5 3 5 56 8 206 In detail
for none of them has been found capable of reproducing itself, the results may nevertheless be of fundamental interest for a better understanding of the nature of life. What the studies do show so far very clearly is that life is indeed an emergent property. The root(s) of the universal tree of life The period between terrestrial formation at around 4.5 Ga (4.5109 years) and the oldest evidence of terrestrial life is less than a billion years (109 years). It is supposed that life established itself on early Earth not longer than 3.93.7 Ga ago during or shortly after the time of the early heavy meteorite bombardment from space, which might have sterilized the planet. New results are indeed evidence for life 3.85 Ga ago (Hayes 1996). This is based on carbon isotope ratios in the Isua rock belt in Greenland, one of the oldest well-preserved sedimentary rocks known on Earth. Life remained at the stage of the prokaryotic cell for more than 2.3 Ga. The mega-step from the prokaryotic to the eukaryotic level only occurred 1.5 Ga ago. It passed then a relatively short time until, prior to approximately 1.0 Ga ago, the first multicellular organisms appeared (Butterfield et al. 1990; Blair and Hedges 2005). According to the majority of analyses of anciently duplicated protein-coding paralogous gene families that are present in all three domains of life, a universal common ancestor first gave rise to the two prokaryotic branches (archaea and bacteria) and the archaea later gave rise to the eukarya (Zhaxybayeva et al. 2005) (Fig. 2). Most of the authors suppose that the last common ancestor was most likely already a prokaryotic cell with ribosomes and energy-conserving membranes not fundamentally different from present-day prokaryotes (Gogarten and Taiz 1992; Laczano 1993; Gogarten 1995). The evolutionary relationship between the three domains of life and the location of the root within the universal tree of life are further hotly and controversially debated questions (Embley and Martin 2006). Due to the horizontal gene transfer that, between prokaryotic species, is perhaps
broadly accepted as the theoretical fully fledged minimal genome. Free-living prokaryotes have a significantly larger genome. No example of a free-living prokaryote with a genome of <1,450 kb has ever been described. The genome of the hyperthermophilic bacterium Aquifex aeolicus has 1,521 protein-coding genes (Homo: about 22,000!) and is capable of autonomous, autotrophic life in an environment containing only hydrogen, oxygen, carbon dioxide, and mineral salts (Deckert et al. 1998). In this connection, approaches based on semi-synthetic minimal cells (Luisi et al. 2006) are of interest. In several studies, liposomes were used as such cell models and filled with extant genes and enzymes. Although these constructions are only poor approximations of a fully fledged cell,
Fig. 2 Left The current standard model of the tree of life showing the evolutionary relationships among living entities. Right A reticulated tree or net, which might more appropriately represent lifes early history (after Doolittle 1999)
far more important, in quantity and quality, than hitherto imagined, early organismal evolution seems more similar to within-species genealogies than to traditional species trees (Doolittle 1999; Gogarten et al. 2002; Zhaxybayeva et al. 2005). In this sense, Woese (2000) hypothesized an undefined progenote community (organisms without a tight coupling between geno- and phenotype) experiencing an extensive lateral gene transfer rather than a single common ancestor was at the root of the tree of life. Forterre and Philippe (1999) placed the root of the tree of life on the eukaryotic branch. They proposed that the ancestors had eukaryotic features and that prokaryotes are the result of regressive evolution. Bapteste and Brochier (2004) claimed radically new approaches. Since the mid-1970s, the endosymbiont hypothesis is widely accepted (Schwartz and Daydoff 1978; Maier et al. 1996). It starts from the assumption that eukaryotic cells are conglomerates (mosaic-cells; Fig. 3): In a first endosymbiotic event probably occurring between 2.2 and 1.5 Ga ago, the early Proterozoic archaeal-like host cells incorporate aerobic -proteobacteria (purple non-sulfur bacteria), the precursors of proto-mitochondria. With this pivotal evolutionary event, the first heterotrophic unicellular
eukaryotes appear. A second endosymbiotic event occurs between 1.5 and 1.2 Ga ago. Ancient mitochondriacarrying eukaryotic host cells incorporate coccoid photosynthetic cyanobacteria-like cells giving rise to the plastids. How the nucleus made its first evolutionary appearance is still a matter for discussions. Three competing hypotheses exist (Kutschera and Niklas 2005). During the co-evolution of hosts and symbionts that followed, a large part of the symbiontic genome was transferred into the nucleus of the eukaryotic cell (intracellular horizontal gene transfer), giving rise to the mosaic provenance of the eukaryotic genomes. The mitochondria and plastids therefore no longer have the full genetic information for their own reproduction at their disposal. However, the ribosomes of both mitochondria and plastids still resemble in their ribosomal RNA (rRNA) sequences those found in bacteria and not those in the eukaryotic cells. They are sensitive to tetracycline, just as bacteria are, but not to cycloheximide. The outer membrane of plastids and mitochondria is not a remnant of the eukaryotic phagosomal layer as earlier supposed but resembles in its ultrastructure and function the Gram-negative outer membrane, which agrees strongly with the endosymbiont hypothesis.
Fig. 3 The symbiotic theory proposes that the complex eukaryotic cell arose by a series of symbiotic events in which organisms of different lineages merged (after Kutschera 2006)
Origin of life Largely as a consequence of Louis Pasteurs famous experiments in 1862, which destroyed any belief in contemporary spontaneous generation, the question arose of how life originated in the distant past on Earth. Starting with the famous papers of Oparin (1924) and the independent efforts of Haldane (1929), much theoretical and experimental work has been done and several ingenious and not unreasonable hypotheses proposed, but we have honestly to confess that no biologist or physicist has yet succeeded in coming up with a convincing and generally accepted theory as to how life originated on earth, how the primordial cell might have evolved, and what its structural und functional particularities might have been. Past research on the origin of life was largely based on the elementary idea of molecular evolution according to which life originated from inanimate matter via a spontaneous increase of molecular complexity and specifity: bottom-up approach. Starting from the classic experiment of Miller (1953), numerous experiments have clearly shown not only that a wide range of biologically significant organic compounds can be synthesized under possible primitive Earth conditions but also that other important molecules resist prebiotic synthesis in acceptable quantities in a primeval soup. This concerns mainly the formation of ribose (and other sugars) and pyrimidines and polymerization in an aqueous solution. Ribose has surprisingly short half-times for decomposition at neutral pH (73 min at 100C; Larralde et al. 1995). It also concerns the formation of membranogenic lipidslinear fatty acids with a sufficiently long (more than 1012 C-atoms) hydrophobic chain. To overcome these shortcomings in the primordial soup hypothesis, Wchterhuser (1988) suggested that the earliest stages of life occurred in a surface-bonded autocatalytic chemical network consisting of polyanionic organic compounds on the positive charged surface of pyrite (FeS2): iron-sulfur-world. Under these conditions, the reactants do not drift away but are kept in each others proximity. This permits not only sufficiently high reaction rates but also the growth of lipid-covered surface areas and subsequently the building of semi-cellular structures by abstriction (individualization). The crucial step of spatial segregation in a chemical environment, the formation of a microscopic membranecovered organic blob around the primeval RNA or DNA (compartmentalization problem) involves, from the point of view of a biologist at least, three essential events: firstly, the separation of the first cell from its environment by a selectively permeable plasma membrane, guaranteeing a controlled exchange of matter and energy with the surroundings (individualization); secondly, the manifestation of an internal functional that means teleonomic order
(organization); and thirdly, the creation of information coding replicative structures guaranteeing the informational integrity and invariance of the system (self-maintenance). The fact is that even the humblest organism must be a coalition of a high number of molecules of different species. It is also a fact that, in living beings, the genetic message can only be translated by the products of its own proper translation and that these products have no future without nucleic acids. To get around this paradoxical situation of nucleic acids being needed to encode proteins and proteins (enzymes) being needed to replicate nucleic acids, Walter Gilbert, Leslie Orgel, and others proposed an RNA world. They believe that the progenitors of modern cells were based entirely on RNA molecules able to act as both informational molecules and catalysts. Only later did proteins take over the role of enzymes and DNA appears to store the genetic information, leaving RNA to mediate between genes and enzymes. This scenario has gained a large measure of acceptance within the scientific community. In this context it is, however, important to point out that years of careful effort to find an enzyme-free polynucleotide system able to undergo replication cycles by sequentially and correctly adding the proper nucleotide to the newly synthesized strand have not yet succeeded (Kaufmann 1996). Another problem is that, under the conditions of the primeval soup, DNA is more likely to accumulate than RNA because it is more stable than the more reactive RNA. The spontaneous formation of a selfreplicating RNA-familythe molecular biologists dream (Joyce and Orgel 1993)is certainly not a trivial process (Luisi 1999). Despite several brilliant reflections and outstanding experiments on this subject, we must assume that there is still an unbridgeable hiatus between the prebiotic organic chemistry and primordial cells. The gap between life and lifeless has actually become wider rather than smaller as cytology, microbiology, biochemistry, and molecular biology have advanced. Ignoring this fact is both unhelpful and dishonest. With Jacques Monod, we must honestly admit that here we reach a real sound wall (Monod 1972). Nowadays, studies on the origin of life have changed from an area dominated by speculation into a field of testable hypotheses.
Life means performance of complex systems: dynamics The conclusion we can draw from the text above is: Life is not substance, it cannot adequately be defined by an inventory of its material constituents. There is no phenomenon in living systems that is not molecular, but there is none that is only molecular, either. We must reject all life-
as-things hypotheses because life is first and foremost a processit represents a dynamic activity and it is performance of a system of singular kind. Living entities must be considered as systems with well-defined spatial boundaries and subject to network dynamics in the sense of general systems theory and not as bundles of linear chain reactions programmed with micro-precision. Living systems actively remain in a state far from thermodynamic equilibrium. As Erwin Schrdinger (1944) pointed out: It is by avoiding the rapid decay into the inert state of equilibrium that an organism appears so enigmatic. Life is a permanent struggle against destruction. This view is by no means new. Already in the eighteenth century, Georg Ernst Stahl saw life as a conservatio mixtionis corporis against the tendency to decompose. Unlike non-living matter, living cells are continually doing something, metabolizing, exchanging material with their surroundings, moving, and so on. They remain in a state of constant flow. When inorganic systems are placed in a uniform environment, sooner or later all motion usually comes to a standstill (equilibrium). Steady state far from equilibrium, entropy At the temperature of existence, the living state is unstable. Every cell exists in permanent breakdown and resynthesis. To live is to be involved in an uninterrupted process of selfrenewal. There is no stagnation; everything is in constant flux. Living systems represent a state of being and a state of becoming at the same time. This continual process of renewal is not one among many attributes of life but the characteristic mode of existence of living systems. Life is a continuous process; life is dynamics. Nothing is excluded, from the superficial plasma membrane to the inner cytoplasm and cytoskeleton. Within 17 days, half of the protein molecules of an adult rat have disappeared and been replaced. Most messenger RNA (mRNA) molecules are destroyed shortly after they are synthesized. Even the DNA molecules are subject to permanent breakdown, liable as they are to be damaged by a variety of agents. Only through permanent restoration is the DNA able to preserve the information stored in it. In order for this permanent cycle of reconstruction to proceed at a sufficient rate at the temperature of existence, catalysts for the many metabolic reactions are necessary. This central function is filled by special proteins and proteids known as enzymes. There are currently more than 2,000 known enzymes, and virtually, all metabolic reactions depend on these compounds, which speed up reactions in a more or less specific manner. Enzymes cannot change the overall free energy change of a reaction. They lower the transition state energy (G) needed to prime the reaction and thus increase the rate of reaction. These increases range from 108 to 1020 relative to the uncatalyzed, spontaneous reaction.
Thermodynamically, organisms are open systems, for they maintain a continuous exchange of matter and energy with their environment in order for life to go on, during which both the chemical composition and the energy content of the system remain almost constant. To maintain the appropriate mix and concentration of chemical components, the degradative processes must keep pace with synthesis; the input must balance the output. We call this time-independent state steady state or Fliegleichgewicht (Ostwald 1926). With respect to the entropy S of the system, this means that the entropy permanently produced inside (diS) the system must be exported into the surroundings (deS). Only in this way the complete entropy S of the system can be fixed at a certain level (dS=0) (Prigogine 1947): dS di S de S 0 di S de S This entropy export requires free energy or enthalpy. The free energy taken by the living organisms from their surroundings in the form of nutrients or sunlight finally returns to the environment as heat and entropy. The order permanently produced in the living cell is more than compensated for by the disorder, which living things create in their surroundings. Strictly speaking, the steady state is not a state of equilibrium but a state of non-equilibrium because it does not coincide with the thermodynamic equilibrium characterized by a minimum of free energy and a maximum of entropy. A system in the state of thermodynamic equilibrium cannot perform work or organize itself. It is simply incapable of living. The maintenance of a steady state far from thermodynamic equilibrium is a prerequisite to being alive. This means nothing more than that the cell itself has to actively maintain non-equilibria against the second law of thermodynamics. The extension of thermodynamics to open systems under far-from-equilibrium conditions beyond the linear domain, where linear relations between the general thermodynamic fluxes and forces no longer exist, by Ilya Prigogine and others of the last century showed us that, under these conditions, systems can also arrive at a permanent state, but one which is no longer characterized by an extreme value of a certain potential and which thus no longer displays the stable behavior immune to fluctuations we know from systems at or around the chemical equilibrium. Glansdorff and Prigogine (1971) termed steady states that are separated from thermodynamic equilibrium by instabilities dissipative structures, as they must be generated and maintained by dissipative or entropy-producing processes. For the occurrence of dissipative structures, the open state of the system is a necessary but not sufficient
condition. Further prerequisites have to be fulfilled, the most important by far of which in chemical systems is selfenhancement or autocatalysis. In biological processes, simple autocatalyses are often based on feedback and feed-forward phenomena. The multiple types of these phenomena and the allosteric enzymes that control the metabolism are important causes of the highly nonlinear kinetics in biochemical systems. In addition, many enzymes are bound to membranes that also yield a highly complex and non-linear behavior. Clear evidence for the existence of dissipative structures in metabolism are the numerous examples of periodicities observed in the synthesis or the activity of enzymes (Hess et al. 1978). Living systems maintain a high degree of internal order by dissipating entropy into their surroundings, but organisms are unique examples of dissipative structures since their internal order is self-created, self-maintained, and self-replicated and not the result of external forces in form of chemical, thermal, or other gradients under strict observance. They are informed dissipative structures. This absolute autonomy of living systems operates through informed pathways on the basis of an internal genetic program. The study of dissipative structures may be helpful for a better understanding of lifes origin: order from disorder. The living state and ontogenetic development, however, is based on quite different principles: order from order. It has little in common with inorganic dissipative structure building. Energy In order to understand life properly, it is essential to appreciate its sheer improbability. Alone, the preservation of the living state of internal order requires permanent delivery of energy. In order to prevent the system from decaying to equilibrium, organisms need to take in free energy on a permanent basis. Because cells function at an essentially constant temperature and pressure, heat flow cannot be a source of energy for them because heat can only do work as it passes to a zone or object at a lower temperature. The energy that cells can and must use is the so-called Gibbs free energy G derived from the breakdown of organic fuel molecules such as carbohydrates and fats. Most bacteria, all protozoan, fungi, and animals find these nutritious moleculesready-made organic compoundsin their surroundings (chemoheterotrophs). Contrary to these organisms, the autotrophs are able to synthesize the carbohydrates themselves from carbon dioxide. Cyanobacteria, green and purple sulfur bacteria, algae, and higher plants capture the necessary energy for synthesis from light (photoautotrophs), the nitrifying bacteria, non-photosynthetic sulfur bacteria, and iron and hydrogen bacteria obtain the energy from oxidizing simple inorganic substances such as sulfides and nitrites (chemoautotrophs). The non-sulfur purple or green
bacteria, finally, can also use energy from light but require organic substances (alcohols, fatty acids, or carbohydrates) as carbon source (photoheterotrophs). Almost all of the energy entering the biosphere comes from the absorption of photons and the conservation of photon-absorbed energy by chlorophyll. Both heterotrophs and autotrophs transform the free energy delivered step by step in catabolism into ATP (adenosine triphosphate; Fig. 4) and other energy-rich compounds capable of providing energy for biological activity at a constant temperature and pressure. The energy is dedicated chiefly to three processes: firstly, the resynthesis of lost compounds (synthesis work); secondly, the active transport of molecules and ions (osmotic work); and thirdly, mechanical processes inside the cell (motion work). The energy transfer fundamental to all living systems occurs chiefly by means of the adenosine diphosphate (ADP)ATP cycle. The hydrolytic cleavage (Fig. 4) of the terminal phosphoanhydride bond of ATP ATP4 H2 O! ADP3 P2 H i corresponds to a free energy change of about Go 30:5 kJ mol1 under standard conditions. The actual free energy of hydrolysis of ATP in living cells is much more negative, ranging from 50 to 65 kJmol1. The ATP turnover inside the cell is very high (Sabater 2006). The ATP-ADPsystem in eukaryotic cells is kept at a level, which differs from its thermodynamic equilibrium by 108 to 1010. Via the inner mitochondrial membrane, a H+-gradient of about 200 mV (Nicholls and Ferguson 1992) is continuously maintained.
0
Life means functional, teleonomic order: organized dynamics The openness of the system in a steady state far from equilibrium is doubtlessly a necessary condition for the existence of life but by no means a sufficient one. The living state represents organized dynamics, which means a functional and therefore teleonomic order. Organisms exhibit an admirable regularity and orderliness, unrivalled by anything we encounter in the realm of non-living matter. Following Oparin (1961), several authors like to characterize organisms by three fundamental properties: metabolism, self-reproductivity, and mutability. If, however, we attempt to characterize the living state and not the organism itself, only metabolism still applies as a general expression to describe the self-maintained dynamics of living systems. Metabolism as the entirety of the chemical events in the living system includes the turnover of substances, energies, and information. It guarantees the permanent self-renewal, self-duplication, and self-reproduction of the living systems. Organisms are still in a living state even if they do not
10 Fig. 4 Metabolism represents a unity of energy-releasing catabolism and energy-requiring anabolism. The primary coupling agent between downhill and uphill reactions in living cells from bacteria to humans is adenosine triphosphate (ATP)
propagate or lack mutability. I agree entirely with Monod that evolution is not a property of living beings, since it stems from the very imperfections of the conservative mechanism which indeed constitutes their unique privilege (Monod 1972). The same is true for reproduction. Metabolism is not just an attribute of living systems, it represents the living state itself, which is functionally organized. The living state persists at all times, at every stage of development. No interruption ever occurs, either during embryological development or in the sequence of generations2. The continuity of life is really a continuity of information (see below).
2 Some living entitiesspores of microorganisms, seeds of plants, some lower invertebrates (tardigrades, nematodes etc.)are able to enter into an ametabolic state of cryptobiosis or latent life by undergoing a phase of liquid water loss. This process may result directly from evaporation or arise through vitrification promoted by the synthesis of a carbohydrate matrix accompanied by metabolic depression. Finally, metabolism comes close to being fully arrested. In this actively caused state of frozen life, the organisms are able to resist extreme environmental condition. In the literature, we find several reports of microorganisms being revived after millions of years from Precambrian or Silurian rocks or salt deposits (Dombrowski 1963; Vreeland et al. 2000). It is, however, still an open question whether those microorganisms are truly long-term survivors, or whether artifacts (contamination) could explain the revivals (Kennedy et al. 1994).
What organized means The living state is best characterized by the adjective organized. Living cells are organized wholes. The term organization is a central and very old concept in biology introduced already by Aristotle. For Lamarck, every fact or phenomenon observed in a living body is at once a physical fact and phenomenon and a product of organization (cited in Hall 1969). In this view, living systems differ from nonliving entities not in being non-physical but in being organized. At the turn of the nineteenth century, the concept of organization, that gave living beings the internal law determining the very possibility of their existence (Jacob 1993), became the focus of the naturalists interest. Biology as an autonomous scientific discipline was born. It was no longer enough to observe and describe in detail the resemblances and differences between organismsthe aim now was to work out the general principles common to all living beings: Everything that is generally common to plants and animals, and all faculties proper to each of these beings without exception must constitute the unique and vast subject of biology, opined Lamarck (1815). Biology began to look beyond the diversity of organisms toward the unity of the living world, in an attempt to distinguish living beings from non-living matter. From then
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on, only two realms were distinguished: the inorganic, nonliving, inanimate, inert things on the one hand and the organic, living, metabolizing, and reproducing beings on the other, the latter being united through their internal selfmaintained organization. The study of living beings could no longer be treated as an extension of physics and chemistry, but demanded (although this has repeatedly being called into question over the course of time) new concepts and its own language. To use the words of Robert Rosen (1985): Complexity is not just complication, but a whole new theoretical world with a whole new physics associated with it. The central term organization inherently involves the aspect of functionalitythe teleonomic, purposeful cooperation of structural, and functional elements. Pittendrigh (1993) once asked the famous mathematician John von Neumann what he saw as the difference between order and organization. Von Neumanns short answer was: Organization has purpose, order does not. That is to say: organization is information-dependent, order is not. That which is missing from the thermodynamic images of organization is tied to the concept of function. A system may be characterized as organized only when it is able to carry out certain functions on the basis of cooperation between its components. Organization is a necessarily qualitative concept, which needs information for its specification. Wicken (1987) defined organization as informed constraint for functional activity. A system is always organized with regard to something. The organization of living systems takes care of selfmaintenance and self-reproduction. Therefore, Monod (1972) speaks quite rightly about the teleonomy of organization. Jacob (1993), his colleague at the Pasteur Institute in Paris, moves in a similar direction: Organization is inconceivable without the postulate of a goal identified with life: a goal no longer imposed from without, but which has its origin in the organization itself. It is the notion of organization, of wholeness, which makes finality necessary, to the degree that structure is inseparable from its purpose. Should any part of the cell or organism fail to perform its function properly, the living system will, sooner or later, become handicapped to the point of death. We can summarize that the concept of organization integrates all these properties, which characterize living beings as unique in the natural world: wholeness, invariance, autonomy, functionality, teleonomy, finality, and purposeful behavior. In contrast to human artifacts, the organization of a living being has its origin and capacity for maintenance within itself and is not implanted by the human mind. In the words of Jacob (1993): Organization includes both what makes life possible and what is determined by it. Uexkll (1928) thus defined biology as the science of organization, and Ludwig von Bertalanffy
(1932) saw with good reasons the basis of life in organization. In the same vein, Monod (1972) considered teleonomy an essential property for the definition of organisms. Unlike in biology, the term organization is relatively unknown in physics and chemistry, for good reason. Physicists deal with systems structured by physical forces rather than those structured for function. When physicists use the term organization in the context of self-organization, they are mainly dealing with a process, namely the creation of order out of chaos under strict observance of certain boundary conditions and not with organization in the common sense of this word. In nature, the occurrence of organized systems is restricted to living beings. We know many of the parts and many of the processes, which occur in living systems, but what makes a cell alive is still not clear to us. A definition of the organizational feature common to all living systems would be tantamount to a definition of the living state itself. Therefore, this approach should be central to all Theoretical Biology (Penzlin 1993a). Proteins as the function bearing molecules In all organisms, the proteins play the central role in metabolism. Due to their nearly infinite variety of their molecular forms and chemical reactivities, they are the function-bearing molecules in organisms. Their spatial structure gives them the unique ability to recognize and select their partners and only these partners (ligands, substrates, and receptors) for specific interactions from a most heterogeneous mixture of chemical compounds. Each protein has its particular, specialized task within the cell. Proteins are indispensable not only as enzymes but also as intra- and intercellular mediators. As structural molecules, they provide much of the cytoskeletal framework of cells. They can perform important transport or movement functions. In the plasma membrane, they play an essential role as translocators and receptors. Antibodies are highly specialized proteins. Last but not least, proteins stabilize and control the activity of DNA and RNA. It is estimated that, in every eukaryotic cell around 4,000 to 5,000, different functional proteins are permanently active as enzymes, transport proteins, receptor proteins, etc. in maintaining the living state (the so-called house keeping proteins). The proteins are the intelligent molecules, which bear the knowledge that maintains the organization of the system. In nearly all organisms agreeing, the elementary building stones of the proteins are the same 20 different amino acids. We are far from being able to answer the question of why only these 20 amino acids and no other, and these furthermore only in the L-form, have been elected to form all the different proteins in organisms. Only a
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minute portion of the potentially possible proteins are indeed realized in living beings. The basis responsible for the function of a particular protein, or in other words for its intelligence, is its three-dimensional shape (tertiary structure), which at a given pH, ionic strength, metal ion concentration, and temperature, is mainly determined by the amino acid sequence (primary structure) and stabilized primarily by non-covalent interactions. Proteins make up about two thirds of the organic matter in a cell. A typical cell requires thousands of different proteins, which have to be synthesized in response to the cells current needs. Protein synthesis can account for up to 90% of all the chemical energy needed by a cell for biosynthetic reactions. The proteins are made at exceedingly high rates. A polypeptide of 100 residues is synthesized in E. coli at 37C in about 5 s. In a growing bacterial cell (E. coli), more than 103 protein molecules and about 104 lipid molecules can be synthesized every second, which demands 2106 ATP molecules. The essentially more voluminous and compartmented eukaryotic cells need about ten times longer for the syntheses. Every organelle in a eukaryotic cell performs specific functions and must therefore contain a certain set of proteins. Most of them are synthesized in the cytosol. Specific zip codes or signal sequences direct them to their different final destinations. On the way, many of these proteins have to traverse at least one membrane or need to be integrated into a membrane. Thereby, the signal sequences open protein-conducting channels. Metabolism All living beings differ fundamentally from all non-living entities in their metabolism. Metabolism is not only the release of free energy or the turnover of substances but is the integration of all the chemical processes carried out by living organisms. It represents in unifying catabolism and anabolism a functional and therefore teleonomic dynamic state of high order, which we characterize as organized. It is entirely inadmissible to say that a flame, a growing crystal in a solution or a machine performs something similar to metabolism. The sole aim of such statements is to make the gap between living and non-living as small and unessential as possible and in doing so to make the reductionistic thesis more comprehensible. Even in vitro replication systems (Mills et al. 1967) consisting of an RNAstrand as a matrix, an RNA-polymerase (Q-replicase), and the energy-rich building stones (ribonucleoside triphosphates) have no metabolism. In contrast to living systems, all these systems lack the feature of permanent self-renewal by an anabolism in connection with a catabolism. They represent solely an irreversible downhill catabolism and thus do not differ in any way from other exergonic reactions, which occur in a test tube.
Metabolism is the indispensable basis for the permanent maintenance of the living state. It is more than the sum of chemical reactions. It is the concerted action of numerous processes to pursue the continuity of life. Each of the reactions needs an enzyme, which is itself the result of a series of synthetic steps and informational transmissions. Thanks to new techniques, scientists are now beginning to analyze the network of interactions between the chemical components in the cell (functional genome research) with the ultimate goal of understanding the complex interactome (Rual et al. 2005; Stelzl et al. 2005). Data derived from comparative biochemistry convincingly show that in spite of a great diversity in the structures and lifestyles of extant organisms, there is an inherent unity of life processes at the molecular level. Only a very few chemical processes and structures out of many chemically possible ones have been implemented in living systems. These are the result of natural selection and constituted specific biological adaptations. In all living cells, we find the same or very similar metabolic pathways and energy transfer by adenosine triphosphate. All cells are covered by lipid membranes and use homologous enzymes to generate ion gradients across them. All cells use the same 20 amino acids for the synthesis of their proteins and in all cases exclusively the L-form. All cells use the same four nucleotides for storing and transmitting genetic information and the same (or a very similar) genetic code. Although there are some differences in the mode of transcription and translation, the process is very similar in all cells. The universality of the chart of intermediary metabolism in organisms doubtlessly counts among the most impressive discoveries of the past century. It is highly probable that all extant organisms trace back to a last common ancestor. It is, however, not clear, whether this last common ancestor already possessed all the biochemical pathways we find universally distributed in recent organisms. We must take into account that some of these properties appeared later and spread through horizontal gene transfer. In the opinion of Gogarten (1995) and others, the last common ancestor does not seem to have been fundamentally different from present-day prokaryotes. To pinpoint events of horizontal gene transfer on the tree of lifeso the author continuesa more extensive sampling of species for slowly evolving molecular markers is needed. Metabolism in cells is carried out in aqueous solution or at water interfaces. Water is not only an essential solvent for life on earth but also an important metabolite. The structure of all biomolecules results from their interaction with water. But under no circumstances should we consider the cytoplasm as a homogeneous aqueous space in which chemical reactions occur in the sense of MichaelisMenten kinetics. Singular conditions exist in living cells, which can
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cause considerable deviations from kinetics as observed in test tubes. Cell metabolism comprises hundreds to thousands of different reactions occurring simultaneously or successively in an orderly manner. All this takes place in an unimaginably small space: The volume of the prokaryotic cell reaches about 1015 l, the volume of eukaryotic cells up to 1012 l. This is an order of magnitude, which limits to some extent the unconditional application of the laws of thermodynamics. The concentrations of the compounds involved in the reactions are very low (between 103 and 106 mol/l). In contrast, the concentrations of the enzymes are relatively high and do not differ appreciably from the concentrations of their substrates. As the molecules are not homogeneously distributed throughout, the cell summary statements about concentrations are usually of little indicative value. Regulation of metabolism The extreme efficiency of the chemical machinery of living systems requires extraordinarily precise and efficacious coordination between various activities. Metabolism is a highly sensitive and nevertheless remarkably stable system, which is able to react to disturbances in a senseful manner and adapt itself quickly to specific requirements. This is only possible because the diverse chemical reactions involved are controlled by an efficient cybernetic network (J. Monod), which guarantees the functional coherence of the intracellular chemical machinery. A full understanding of how living organisms function includes an appreciation of how cells operate at the molecular level. The central regulatory compounds in this network are the proteins, in particular, the allosteric enzymes, which can easily switch on or out (Koshland 1987). Regulated enzymes are often found at the start point, end, or branch point of metabolic pathways. Well known is the regulation by negative feedback: The final product of the pathway inhibits the first enzyme in the pathway. It has long been known that metabolic pathways display rate-limiting steps, which are controlled by specialized key enzymes regulating the flux rate of metabolites at this point. The reactions in question unlike most other steps occur far from the chemical equilibrium. They are, therefore, irreversible and strongly exergonic, which means that they exhibit a highly negative free enthalpy (G0; Hess and Boitew 1971). In many cases, the control of the flux rate through a metabolic pathway can occur simultaneously at several or even all steps of the pathway even if with different efficiencies (distributed metabolic control). The molecular geneticist Henry Kacser used in this connection the term molecular democracy (Kacser and Burns 1979). When
yeast cells are placed in conditions, which require a higher energy turnover, they increase the activity of all glycolytic enzymes. The metabolic net has both a functional and a structural basis. The extraordinary protein-rich cytoplasm of eukaryotic cells has a submicroscopic architecture, which consists of a dense network of thin filaments (mainly F-actin; Hou et al. 1990). For a cell with a diameter of 16 m, the surface of this cytomatrix amounts ranges from 40,000 to 130,000 m2. Frequently, essential components of metabolic pathways are found united in genetically, structurally, and functionally defined units, which Srere (1993) called metabolons (Fig. 5). Many enzymes are combined with structural elements, metabolites, and ions in loose transient complexes. One well-known example is the citric acid cycle in the mitochondrial matrix. The bonds are not so tight that the metabolites are prevented from shifting into the free metabolic pool of the cell, which is of great importance because several metabolites have multiple functions as signal molecules, C-sources for other metabolic pathways, or in other way. Teleonomy and purposiveness In every organism, structures exist and processes occur, which in general serve certain purposes and are purposeful for the continued existence of the whole. The components of organisms are interrelated one with another to form a system, which appears to be designed for a particular direction of activity. In other words: Living systems are directive and purposive and, in this sense, teleonomic (Pittendrigh 1958). Nobody can seriously deny that every unicellular and multicellular organism and their various organs (organelles) represent the materialization of functions and adaptations, or to put it another way, nothing less than the materialization of purposes. Already the philosopher Kant (1790) in his Critique of Judgement very rightly characterized organisms as Naturzweck in which each part is conceived as if exists only through all the others, thus as if existing for the sake of the others and on account of the whole, that means as an organ. As Monod (1972) emphasized for good reason, objectivity obliges us to recognize the teleonomic character of living organisms, to admit that, in their structure and performance, they act projectivelyrealize and pursue a purpose. The foundation for the teleonomic project in organisms lies in a certain quantity of information stored in DNA. Anyone who attempts to negate purposes and goals, functions, and adaptations in biological thinking and research omits the bios from biology. Previous to Darwins work, the explanation of this obvious fact was invariably connected with unbridgeable difficulties. Many scientists have held and continue to
14 Fig. 5 Supramolecular association of glycolytic enzymes to F-actin-troponin (after Bereiter-Hahn et al. 1997)
nurture a deeply rooted distrust of the acceptance of aims and purposes in our natural world (Penzlin 1987). More than anyone else, Darwin showed us that a natural, objective explanation of purposiveness is a rational possibility and a legitimate scientific goal. What is most challenging about Darwin, MacLeod (1957) pronounced, is his reintroduction of purpose into the natural world. Darwin exorcised teleology of its transcendentalism. Once organisms are fully conceived in their inherent dynamics as entities created during a long process of evolution by mutation, recombination, competition, and natural selection, it becomes highly evident that purposiveness cannot be something grafted onto the living beings but must be an essential immanent peculiarity of them. If the purposeful cooperation of the numerous processes in preserving the living whole ceases to function correctly, the organism no longer has a real chance of survival and is excluded from further evolution. I believe Pittendrigh (1993) was right when he said for his own part that he would have been happier had The origin of species been called The origin of organization: The non-theological explanation of biological organization (of Pahleys design) was the real Darwinian revolution, much more profound than the origin of diversity, which it incidentally entails. In contrast to the external teleology of certain human artifacts such as target tracking missiles, the teleology of living beings is an internal one because it is inherent to the system and self-made and does not originate from the intention of an engineer. Teleonomic in biology means goal-directed but by no means goal-intentioned. Teleonomy is directiveness without knowledge of the goal, is perfor-
mance according to a plan. It does not make much sense to differ between purposeful and teleonomic as proposed Mayr (1979). Purposiveness always includes a goal to be achieved. Purposiveness is a relation term. It receives its significance only in relation to something else. We can say that a structure is only considered purposeful when the achievement of a purpose, which is at the same time the goal, is facilitated or made possible by it. In every organism, we notice a hierarchy of purposes (Riedl 1981). The uppermost purpose in every case is to ensure the realization and perpetuation of the living state with its specific performances. All other purposes are subordinated to this. Throughout the long process of evolution, the organization of living beings has been perpetually adjusted in such a way that it guarantees their survival and multiplication. While in physics the causal connection soon became the dominating form of explanation, biologists cannot renounce teleonomic formulations and explanations because the objects of biological research are organized and, as such, are purposive and end-directed. Biologists would lose a great deal, methodically and heuristically, if they were prevented from using teleonomic language. That does not mean however that, unlike in physics, causal-analytic research in biology is quite inadequate to its task, as Russell (1945) assumed. Teleonomic and causal-analytic explanations do not contradict but complement each other. A teleonomic explanation appeals to the end of the process. It concerns the function, which the process has to fulfill. The point in
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question is how the process under consideration fits into the general relationships of the whole. A teleonomic explanation does not make the causal-analytic explanation superfluous but invites us to carry out supplemental causal research. Both forms of explanation have their role and importance in life sciences. All efforts to translate teleonomic statements into purely causal ones must fail.
Life means informational integrity and invariance: self-maintained organized dynamics Organisms are endowed with a power to maintain their organization permanently against disruptive influences. Thus, not only does life represent a highly organized dynamic; this dynamic is furthermore self-maintained. Organization implies functionality, which in turn requires structural relationships, and structures require information for their specification. Information in turn presupposes a source, and this source is constituted in living systems by the nucleic acids. In this spirit, organisms may be considered as information systems, too. Organisms are unique in having a capacity to use information, which is stored in the nucleic acid and yields the basis for their specific organization in its perpetuation. A characteristic feature of this information is that it is historically acquired during evolution: Any living cell carries with it the experiences of a billion years of experimentation by its ancestors (Delbrck). Life is not only able to store but also to improve its internal programs. As with other compounds and structures, the intelligent proteins also undergo continuous degradation and must continuously be built de novo. Up to 90% of the chemical energy used by the cell for biosynthesis can be involved in protein synthesis. That means that, in cells, not only a permanent loss of free energy but also of information occurs, which must just as continuously be replaced. Living organisms take the necessary energy from their surroundings in the form of nutrients or sunlight. The source for the necessary information lies inside the organisms. It is stored in their nucleic acids. The genome Proteins cannot be synthesized by enzymes alone since the bonds to be made up between the amino acids in the growing polypeptide chain do not differ from each other. Regardless of the amino acid concerned, the bond is always a peptide bond. Therefore, the linkage of the amino acids in the right sequence requires more than an enzymatic apparatus, it requires a matrix. That in turn means it requires information, and this information is stored in the genome of the cell. The capacity for informational
invariance, the maintaining and multiplying of highly ordered information-bearing structures in the form of nucleic acids, is a further fundamental and unique feature of organisms in addition to their internal functional order (vital organization). Efficient repair mechanisms ensure that the stored information does not get lost: preservation of genetic integrity. It is estimated that, for instance, in every human cell about 5,000 DNA letters get lost every day, which must be instantaneously restored. The existence of a genomethe complete genetic endowment of an organismis a necessary condition for the living state and one of the absolute differences between living and non-living matter. Organisms represent a new principle, the order-from-order principle (Schrdinger), which is the clue to understanding life. The importance of genomes for the organisms lies in the fact that they contain the instructions for the construction of the peptides and the program for the control of their synthesis. Human beings do not differ from E. coli bacteria in a more efficient chemistry but in more information. Mycoplasma has about 500, E. coli approximately 4,000, yeast 7,000, fruit flies 13,000, nematodes 18,000, and man 35,000 genes. However, we still have no idea what the function of most genes might be. Although humans evolved relatively recently, the human genome is very old. Of 1,278 protein families identified in one early screen, only 94 were unique to vertebrates. Every organism carries with it a lot of information acquired by its ancestors during the past three billion years. While the number of genes has a 100-fold range, the amount of DNA ranges from 5106 to nearly 50109 base pairs (bp). That is a 10,000-fold range! This is due to the increased non-coding DNA in eukaryotes with a larger DNA content. The non-coding DNA is not only found between genes (intergenic DNA) but also as so-called introns inside the genes interrupting the coding sequences. In some genes of higher eukaryotes, the introns may occupy 90% or more of the DNA. The complete sequence of the human genome published in April 2003 contains 3 109 bp. Only about 1.4% of the genome codes for proteins. More than 50% of our genome consists of short repeated sequences (repeats). About 45% of our genome come from transposable elements (transposons). The human genome contains for instance 1.8 million copies of the transposon short interspersed element (SINE) and 1.4 million copies of the transposon long interspersed element (LINE). Usually, the genome (in man with the single exception of the lymphocytes in blood) is the same in all somatic cells. Gene expression can be regulated at the level of gene transcription, nuclear RNA processing, mRNA translation and/or protein modification. Only a fraction of the genes is switched on at any given time: in a typical bacterial cell about 25% of the 1,000 genes. Genes that are needed all the
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time are expressed constitutively. These are known as housekeeper genes. They are required for the fundamental operations of the cell. The majority of genes are only needed (expressed) under certain environmental conditions, in particular tissues, or at certain stages of development. Cell differentiation leads to many different cell types with particular patterns of gene activity, which determine which proteins are synthesized. These patterns can be maintained over long periods of time and can be transmitted to the cells progeny. The expression levels of large numbers of genes in a tissue can now be determined simultaneously by DNA microarrays. All these complex processes of gene regulation do not occur spontaneously but require the chemical machinery of the living cell in the form of enzymes, transcription and initiation factors, tRNAs, ribosomes, etc. They are tightly integrated in the general cell metabolism and need energy. Every attempt to isolate life from its systemic dependencies and reduce it to the genomic level, as Richard Dawkins and others have tried, necessarily leads astray. An autonomous life of genes, a genobiosis (Kaplan), does not exist. Genes are neither selfish nor motivated in any
Fig. 6 The double stranded DNA forms a double helix (after Bruce Alberts et al. 1995). The genetic code: A codon consisting of three bases determines each amino acid to be added to a growing polypeptide chain. Three of the codons act as stop signals. AUG encoding methionine, acts as a start codon
other way. Living systems display an essentially causal circularity: Proteins (enzymes) require information (DNA) and DNA requires enzymes. The machinery by which the cell translates the codes consists of several components, which are themselves coded in DNA. That means the code cannot be translated except by using certain products of its translation. It is fruitless to ask what came first, the proteins or the nucleic acids. Both are equally necessary. Only from this essential basis does the living system draw its typical capacity to maintain its vital organization. In this regard, Wicken (1987) once defined an organism as an informed autocatalytic organization. Nucleic acids as the information-bearing moleculesthe genetic code Genetic information is stored in linear molecules, so-called polynucleotides. There are the double-helical deoxyribonucleic acid (DNA; Fig. 6) and the single-stranded RNA. The genetic program in nucleic acids is coded by the specific sequence of the different nucleotides. This code transmits the maximum amount of information if the same chance for
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incorporation exists for each of the four bases at all sites of the sequence. It is this physical indeterminacy that produces the possible information content of a DNA molecule. The polynucleotides have unique features that predestine them for their central role in storing and transferring the genetic information required for assembling the various proteins essential to the proper functioning of the living system. Firstly, they are unique in their capacity for replication, provided some environmental conditions are fulfilled. Secondly, they can exist in an almost infinite number of different variants resulting in an inexhaustible reservoir of different programs, which can code for different proteins. Only a tiny fraction of this reservoir has been tried out in life so far: The actual is an exceedingly small part of the possible only (Jacob 1982). DNA molecules store the genetic information but cannot serve as a direct source of instruction for the living cell. In order for the cell to be able to use the information, a working copy of the DNA must be carried on RNA. For this reason, the double-stranded DNA must temporarily be pulled apart into the template and the coding strand. On the template strand, a complementary RNA strand arises. The sequence of the RNA strand is identical to the sequence of the coding strand apart from the replacement of the thymine in DNA with uracil in RNA. This so-called mRNA subsequently converts the genetic information into the proteins. The genetic message can do nothing by itself. It requires an intact cell in order to be able to fulfill its function. Outside the cell, the stored genetic program remains inert. Only cells possesses both the program and directions for use, the plans and the means of carrying them out by the proteins (Jacob 1993). The mechanism of protein synthesis demands highly specific chemical correlations, which cannot occur with the necessary efficiency (in a normal mammalian cell more than 106 peptide bonds can be joined within one second!) in free solution in the plasma. Overall, almost 300 different macromoleculesmany of them localized in the complex ribonucleoprotein particles, known as ribosomescooperate to synthesize polypeptides. The ribosomes, aggregates of two sub-units consisting of proteins and rRNA, are the cells protein factories, found in both prokaryotes and eukaryotes. They decode the nucleic acid-encoded information on the mRNA to make proteins. In nucleic acid molecules, a group of three successive basesa so-called codoncodes for a specific amino acid (Fig. 6). Several amino acids are specified by more than one codon (synonym codons). The codons are read in a successive, no overlapping fashion. The beginning of a polypeptide is signaled by an initiation codon (AUG). It establishes the reading frame, in which a new codon begins every three-nucleotide residues. The so-called stop codons normally signal the end of polypeptide synthesis (termina-
tion codons). In the case of eucytes, the coding exons are separated by non-coding introns, which must be removed by splicing before the exons can be joined to the mRNA. The genetic code is, with a few exceptions, nearly identical in all organisms (universality of the genetic code): Rare exceptions are found in some protozoan and mycoplasmas and in the mitochondrial genome of animals and fungi. Strictly speaking, it is not a code in the customary sense of the word but a correlation schedule for the translation of the sequence of bases in the polynucleotide (DNA) into the sequence of amino acids in the polypeptide (protein; Kay 2000). All talk of genetic code is metaphorical. There are, in principle, two explanations for the universality of the code: Either all organisms descend from one simple ancestor whose more or less accidental code (frozen accident, Crick 1968) has persisted relatively unchanged to date or there exists an optimal code on which the different living forms have converged in the course of evolution. Computer simulations show that the susceptibility of the natural genetic code to mutative changes is considerably lower than in alternative artificial codes. Only one code out of one million tested had a lower susceptibility (Freeland and Hurst 1998). This property of the natural genetic code makes it particularly suitable for evolutive adaptations (Freeland et al. 2003). We must assume that the genetic code arose very early in lifes history 3,500 million years ago, before the division into the three phylogenetic tribes: bacteria, archaea, and eukarya (Eigen 1987). This does not mean that life must only have originated once, just that living beings with the code in question prevailed against all competitors with other codesshould they have existed. The paradigm of self-organization This self-movement of all living beings (Platon), this coming-out-itself, this self-determination may be called the vital self-activity of living systems. Often underemphasized, it is an essential feature of living beings and one, which characterizes them as fundamentally different from the rest of nature. Roux (1895) called this phenomenon Autoergie. Outside forces may threaten the existence of living beings, but they are totally unable to alter the organization of living beings, which is exclusively inherently determined. In science, the term self-organization has been broadly accepted and has become very popular in many different scientific branches such as physics, astronomy, neurobiology, psychology, and sociology. It is celebrated as a revolution of our scientific Weltbild, a new paradigm (Kratky 1990) and a principle inherent in the dynamics of the universe from the Big Bang to the appearance of human mind (Jantsch 1984). Similar formulations are found in Cramer (1993): Self-organization of matter to produce
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life may be understood as a physical principle. Since the Big Bang self-organization has been a physical attribute of matter, just as mass is a physical attribute of matter. Capra (1988) goes as far as to state: Dissipative chemical structures represent a connecting link between living and non-living matter. Whether one calls them living organisms or not, is ultimately a matter of agreement. Such unfounded generalizations and inadmissible simplifications lead astray and have led to the term self-organization often being used nowadays as a meaningless catchword. It is only admissible to speak in this connection of a new paradigm in science in the sense of Kuhn (1962) if the application of this concept of self-organization to the event under consideration brings a real and not only a pretended progress in our knowledge. In the main, this is not the case. When physicists use the concept of self-organization in connection with dissipative structures, they usually have the formation of order but not of organization in mind: order from disorder. Inorganic dissipative structures, as for instance, the RaleighBnard convection pattern, the chemical reaction waves in the BelousovZhabotinsky system or the laser, are at the most metaphors but by no means paradigms of biological structure formation processes (Penzlin 1993b). They appear as the result of a cooperative dynamic (Haken) through a certain range of thermodynamic gradients such as temperature or reactantproduct concentrations, for instance. They disappear immediately when the external applied boundary condition no longer exists. They neither have a teleonomic character nor represent a functional order, which means that organization is lacking. For this reason, they do not require information for their specification either. They lack a self. There is still a big gap between the dissipative structures of simple non-living systems and those associated with living systems. In contrast to all artifacts, living organisms display an unrestrained self-determination of forms and performances. Life is not merely a programmed activity but self-programmed activity (Thorpe 1978). Environmental conditions may modulate events by enhancing or limiting certain processes, but they cannot determine or change the teleonomic character of the processes themselves. Due to a variety of cellular mechanisms, including negative feedback and redundancy, the embryonic development is remarkable consistent and reliable. Practically nothing is left to chance, unlike in the case of the formation of clouds in the sky or the turbulence in a jet of water. The decisions are made; they do not represent accidental symmetry breakings (Penzlin 1988). The genome contains a program of instructions for making the organism. This program is generative, not descriptive (blueprint), one in which numerous activitiesgenes and cytoplasmic constituents are more or less directly integrated in order to produce and
maintain the organizational relationships that form the identity of that system. In contrast to all inorganic systems, life involves informed replication through transformational activities. It is not true, that the physical concept of synergetics, as developed by Hermann Haken and others, provides already the basis for a better understanding of organisms and their relationships with their surroundings (Kelso and Haken 1997). The open character of the system and the remote-from-equilibrium order are doubtless necessary conditions for the existence of life, but they are by no means sufficient. It is an illusion to think that the organization of living systems can be maintained in the long run without a genome or would be understandable without its genetic-informational foundation. The term self-organization in physics is a rather infelicitous expression because it is erroneous. For dissipative structures, the appellations self and organization are ambiguous. The terms create associations, which run counter to the true situation relations. The only systems that are self-organizing and self-organized in the true sense of the word are only the living entities in our natural environment, for only they represent a state of functional order that we can class as autonomously induced and maintained organization. We can summarize that the maintenance of specific organization is the essence of life. If a working definition of life is to be found anywhere, it must be found in the distinctive character of vital organization (Wicken 1987). This is by no means an entirely new insight. Kants (1790) important Critique of Judgement contains the extremely modern sounding sentences that the organisms are self-organizing beings whose parts altogether and reciprocally create a whole of their own causality. Life as an emergent property The fundamental laws of physics and chemistry also apply to living beings, but they are not sufficient to explain the most important phenomena of vital organization, such as individuality of form and behavior, autonomy, functionality, teleonomy, etc. Our world displays a hierarchical structure. We can distinguish various levels of existence starting with elementary particles, continuing upwards to the level of atoms, molecules, cells, and finally to the level of multicellular organisms and supra-organismic associations such as populations and communities. As we go from one to the next higher level, entirely new properties appear and new concepts emerge. Each level in the hierarchy has its own body of laws and constraints and needs its niveau adequate terminology. This statement goes already back to Mills (1843) Logic. Having knowledge of the basic constituents does not permit one to build up an understand-
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ing of the total system. The hydrogen atom has properties, which we neither find in the single electron nor in the single proton particle, the water molecule has properties possessed neither by single hydrogen nor single oxygen atoms, and water has properties that we do not find in single water molecules. Organisms are not just heaps of molecules. They exhibit regularities, which have as much legitimacy as the fundamental laws analyzed so successfully by the analysts. Even if we know everything about every single molecule in a muscle cell, we cannot derive from this how the cell works. The appearance of new qualities as we move upwards from one hierarchical level to the next is called emergence. Emergent properties result from the particular way in which the parts of a complex system are integrated to form a whole. The concept of emergence, introduced by Lewes (1879), claims that the whole is more than the sum of its parts. Being alive is indeed such an emergent property of cells. Living systemsand this is also true for machinesare only understandable in context of their functionality, and functionality implies structure as a conditio sine qua non. What makes organisms unique is not their deliverance from the universal laws of physics and not the possession of a particular vis vitalis, but the apparent multitude of initial and boundary conditions that must be determined in order to bring the laws to bear upon them (Rosen 1985). Following the physicist Polanyi (1968), we can consider structures in the physical sense as a set of boundary conditions harnessing the physicochemical processes by which the organs perform their function. Boundary conditions introduce new principles, which we cannot derive from the physicochemical laws and forces; they are only understandable in the context of their function. They harness the laws of inanimate nature, but are themselves irreducible to those laws. In living systems, only an extremely small selection of the possible chemical reactions is realized at any moment. These rules of order, which rigorously restrain the possibilities, are the feature that distinguishes the living state of any organism in fundamental way from the dead state which is characterized by chaos and autolysis. These higher principles do not interfere with the laws of physics and chemistry; they are additional to them. In this process of so-called downward causation (Campbell 1974), genuinely novel properties and processes emerge, which cannot be explained by the material properties of the components. Neither the structure of machines nor the structure of living entities can be defined in terms of the laws, which they harness. They transcend the laws of physics and chemistry. The higher level laws operate as selective systems or restraints on the lower-level processes. The efficient causes are higher level boundary conditions, which are general principles, and the effects are selective
activations of concrete lower level causal processes (van Gulick 1993). Hulswit (2006) remarked that the term downward causation is somewhat badly chosen because it is usually understood in terms of explanation and determination rather than in the sense of bringing about3. Boundary conditions need information in order to come into existence. In the case of human artifacts, the source of the essential information is outside the machine in the brain of the constructor. In contrast to these human-made machines, the structures of the wholes and parts of living beings are not shaped definitively by a constructor during morphogenesis but by the transmission of information stored internally in the genome. The wonderful skeletons of the radiolarian (Fig. 7), which once fascinated Ernst Haeckel, are not understandable within the framework of physics and chemistry. They are the manifestation of an internal program stored in the genome of these organisms. Nobody will contest that all matter, including organisms, consists of atoms. Furthermore, nobody will denynot even the vitalists nowadaysthat all physical laws are fully valid in organisms, too. That is not the issue. However, it most certainly does not follow that organisms are nothing else but an ensemble of atoms and the interactions occurring between them. It is not true that organisms and everything that living things do can be understood in terms of the jigglings and wigglings of atoms (Feynman et al. 1989). This statement does not even apply to human artifacts: Nobody would try to understand or explain the function of a clock, steam engine or computer in terms of the jiggling and wiggling of atoms. And it remains wrong even if we replace the term atoms by molecules. Biology and physics The so-called exact sciences have some difficulties in trying to incorporate organisms into their Weltbild. Physicists try to simplify and idealize systems and phenomena and have concerned themselves with the formulation of universal laws. In their opinion, there is no new physics to be learned from organisms: Physics deals with the general and biology concerns only the particular. In the opinion of several outstanding physicists and molecular biologists, life can completely be understood in terms of the laws of the inanimate, physical universe. With the words of James
Moreno and Umerez (2000) consider downward causation in terms of formal causation, which they relate to the concept of information. In Aristotelian termsso the authorswe can say that DNA molecules are the formal cause of proteins ..., because their specific sequence of nucleotides convey the dea or form of the latter. The informational components of the DNA constraint the lower-level chemical reactions that constitute the cell.
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Fig. 7 Radiolaria (after Ernst Haeckel)
continue to call the resulting united science physics or find a new name for it is of minor interest. In the light of a future Theoretical Biology and of his own experiences with this subject, Nicolas Rashevsky once raised the legitimate question: We have supposed that we can resolve an organism into physical subsystems, understand each of these in detail through traditional modes of physicalinvestigation, and when we are done, the original biological organization to which thesesubsystems belonged will reemerge of itself. This has not happened. Why do we not then start with the organization? Why do we notabstract away the physics and the chemistry, leaving us with a pure organization, which we can formalize and study in completely general abstract terms; and recapture the physics later through a process of realization? (Rosen 1985). The aspired unified theory as a general framework into which the various specialized disciplines of physics had to be fitted might ultimately be completely general in the sense of applying to all material phenomena, it can cover only the features common to all the members of its reference class; hence, it will miss all peculiarities (Mahner and Bunge 1997). It is, as George Gaylord Simpson (1963) wrote, essentially a search for a least common dominator in science. It necessarily and purposely omits much the greatest part of science, hence can only falsify the nature of science and can hardly be the best basis for unifying the sciences. In the same direction pointed the physicist Anderson (1972) with his statement: The more the elementary particle physicist tell us about the nature of the fundamental laws, the less relevance they seem to have to the very real problems of the rest of science.
Watson: there is only one science, physics; everything else is social work. The concept of functionality and with it the aspect of self-produced and self-maintained organization is of central importance in biology and quite unknown in physics. Therefore, all efforts to explain the phenomenon of life in terms of physics and chemistry are doomed to fail because these approaches cannot discern the complex integration necessary for specific biological organization and for the purposeful behavior of living beings. It will never be possible to explain all biology in terms of physics and chemistry (Crick 1966). I agree with Kaufmann (1993) that the origins of order are to be found in the generic properties of living matter itself and only there. Complexity is not just complication but represents a new theoretical world with new physics associated with it. It is not biology but physics that deals with too limited, too restricted class of systems (Rosen 1991). Physics will continue to extend its field so that its theories and rules some day cover also the complex beings and becomings of the living world, too. Whether we will
Rsum: life as an end in itself In spite of the enormous richness of living forms and performances in the biotic realm, there is a considerable uniformity in the chemical machinery of life, which powers all present-day organisms, from simple bacteria and fungi to higher plants and animals including ourselves. All organisms are cellular and use the same 20 L-amino acids for the synthesis of their proteins and the same five nucleotides in their nucleic acids. In all cellswith only a few exceptionsa nearly identical code is realized. The genetic information is stored in the DNA, transcribed into RNA andlastlytranslated into proteins. These complex processes of transcription und translation are very similar in all cells. All cells are covered by lipid membranes and use homologous ion-translocating ATPases to generate ion gradients across them. Both the main metabolic pathways and the energy transfer by ATP are ubiquitous. While the proteins as the intelligent compounds carry out most of the cells routine functions and in this way
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guarantee the organized dynamics of living beings, organisms owe their informational invariance and integrity, their personal specifity, their self through a permanent cycle of breakdown and rebuilding to the nucleic acids, and the information bearing molecules. Just as we think of ourselves as real and continuous over a life time, while knowing that we contain very few of the atoms with which we were born, so every living entity exists during its lifetime in its self. What makes living beings singular and unique isfirstly their state of functional dynamics, or teleonomic order, which we call vital organization, andsecondlytheir ability to autonomously maintain and replicate this organizational state far from thermodynamic equilibrium by virtue of information, stored and used internally. The internal self-maintained vital organization of living systems needs a continuous flux of energy and information. The energy the organisms find in their surrounding, the information in their self. Living entities are thermodynamically open but organizationally closed systems. Organisms are autonomous programcontrolled self-maintaining and self-reproducing entities. A state of more or less alive does not exist. Therefore, it makes no sense to distinguish between seven different forms of life all with different characteristics, as Fong (1968) tried in his attempt to establish a general theory of life. The phenomenon of life is to be considered not so much as consisting of things such as particles, atoms, and molecules but in terms of relational and organizational properties (Hull 1974). In living systems, information processing has somehow gained the upper hand over the dynamics of matter and energy that dominates the behavior of most non-living systems. The organization of living beings owes almost nothing to the action of external forces but everything to internal informational interactions. Through this autonomy, living beings are distinct from human artifacts. Only living beings are really self-organizing and self-organized in the true sense of the word. Machines are designed in the interest of external outputs. Their operations can be kept distinct from their existence. There is no need for them to degrade free energy to maintain their own existence. In organisms, on the other hand, existence is inseparable from operations. Self-maintained organization is not an attribute but the mode of being of living systems. It provides for the development, maintenance, and propagation of entities. There is no separation between producer and product; the two coincide: being and doing, structure, and function form an inseparable unit. I avoid in this connection the term autopoiesis introduced by Maturana because it is philosophically loaded (radical constructivism) to such a degree that it has become useless for the biologist (Penzlin 2002). Biology is currently advancing as rapid as physics did at the beginning of the twentieth century. Enormous progress in the understanding of complex phenomena has been made. Nevertheless, many
riddles remain for science to solve, and life is perhaps the most interesting among them but at the same time one of the most difficult. Living creatures remain, as Jacques Monod once wrote, rather strange objects. One cannot solve the riddle of life by ignoring the immanent teleonomy, purposiveness, and autonomy of living beings just because these properties do not fit our mechanically imprinted Weltbild. Only patient research will advance our understanding, one step at a time. I cannot agree that biology will not become lawful until the set of biological entities under study is vastly extended beyond the set originally provided to us by nature, as Langton (1995) claimed. This, as we know, is the primary motivation behind the field of research erroneously referred to as Artificial Life: To give us a glimpse of that wider space of possible biologies. It is highly uncertain whether such realm beyond biology really exists and to a certain extent pure science fiction to speculate that it might. The human-made electronic (computeral) systems grandiloquently heralded as artificial life that imitate some of the properties of natural life are far from actually being artificially created life. The same is true cum grano salis for the project called Artificial Intelligence. I have tried to discuss critically various aspects of the nature and singularity of living beings, and I have done so from the biologists point of view. Consequently, my view of things is necessarily incomplete. As a naturalist in the tradition of Ren Descartes, I restricted my attention to the material phenomena, the res extensa, knowing well that in the higher animals at least there exists something else, namely the immaterial mental phenomena. Nobody really knows how common consciousness is and how it is related to matter. Is consciousness a universal property that organisms experience to varying degrees but fundamentally alike in kind? Or, how could mind and consciousness have been produced by Darwinian evolution? Here, we touch upon one of the deepest and most puzzling questions that the universe has thrown up, the Weltknoten of Arthur Schopenhauer. Emil Dubois-Reymonds ignoramusignorabimus is not yet refuted.
References
Alberts B, Bray D, Lewis J, Raff M, Roberts K, Watson JD (1995) Molekularbiologie der Zelle. 3. Aufl. VCH Chemie, Weinheim Anderson PW (1972) More is different. Science 177:393396 Bamford DH, Grimes JM, Stuart DJ (2005) What does structure tell us about virus evolution? Curr Opinion Structural Biol 15:655663 Bapteste E, Brochier C (2004) On the conceptual difficulties in rooting the tree of life. Trends Micobiol 12:913 Bereiter-Hahn J, Airas J, Blum S (1997) Supramolecular associations with the cytomatrix and their relevance in metabolic control: Protein synthesis and glycolysis. Zoology 100:124
22 Bertalanffy L v (1932) Theoretische Biologie. 1. Band: Allgemeine Theorie, Physikochemie, Aufbau und Entwicklung des Organismus. Gebr. Borntraeger, Berlin Blair JE, Hedges SB (2005) Molecular phylogeny and divergence of deuterostome animals. Mol Biol Evol 22:22752284 Breitbart M, Rohwer F (2005) Here a virus, there a virus, everywhere the same virus? Trends Microbiol 13:278284 Brcke E (1851) Die Elementarorganismen. Sitzungsber Kgl Akad Wissensch in Wien, Mathem.-Naturwiss. Klasse 44:381466 Butterfield NJ, Knoll AH, Swett K (1990) A bangiophyte red alga from the proterozoic of arctic Canada. Science 250:104107 Campbell DT (1974) Downward causation in hierarchically organized biological systems. In: Ayala F, Dobzhansky T (eds) Studies in the philosophy of biology. University of California Press, Berkeley, pp 179186 Capra F (1988) Wendezeit. Bausteine fr ein neues Weltbild. Droemersche Verlagsanstalt Knaur Nachf., Mnchen Cramer F (1993) Chaos and order. The complex structure of living systems. VCH, Weinheim Crick F (1966) Of molecules and man. Univ. of Washington Press, Seattle Crick F (1968) The origin of the genetic code. J Mol Biol 38:367379 Deckert G et al (1998) The complete genome of the hyperthermophilic bacterium Aquifex aeolicus. Nature 392:353358 Dombrowski HJ (1963) Bacteria from palaeozoic salt deposits. Ann NY Acad Sci 108:453460 Doolittle WF (1999) Phylogenetic classification and the universal tree. Science 284:21242128 Eigen M (1987) Stufen zum Leben. Die frhe Evolution im Visier der Molekularbiologie. Piper Verlag, Mnchen Embley TM, Martin W (2006) Eukaryotic evolution, changes and challenges. Nature 440:623630 Feynman RP, Leighton RB, Sands M (1989) Lectures of physics, vol.1. California Institute Technology, Pasadena, CA Fong P (1968) Phenomenology theory of life. J Theor Biol 21:133152 Forterre P, Philippe H (1999) Where is the root of the universal tree of life? Bioessays 21:871879 Freeland SJ, Hurst LD (1998) The genetic code is one in million. J Mol Evol 47:238248 Freeland SJ, Wu T, Keulmann N (2003) The case for an error minimising standard genetic code. Orig life 33:457477 Gil R, Silva FJ, Peret J, Moya A (2004) Determination of the core of a minimal bacteria gene set. Microbiol Mol Biol Rev 68:518537 Glansdorff P, Prigogine I (1971) Thermodynamic theory of structure, stability and fluctuations. Wiley, New York Glass JI et al (2006) Essential genes of a minimal bacterium. Proc Natl Acad Sci USA 103:425430 Gogarten JP (1995) The early evolution of cellular life. Trends Ecol Evol 10:147151 Gogarten JP, Taiz L (1992) Evolution of proton pumping ATPases: rooting the tree of life. Photosynth Res 33:137146 Gogarten JP, Doolittle WF, Lawrence JG (2002) Prokaryotic evolution in light of gene transfer. Mol Biol Evol 19:22262238 Haldane JS (1922) Respiration. New Haven, London, Oxford Haldane JBS (1929) The origin of life. The Rationalist Annual 148:3 10, (reprinted in: Bernal JD, 1967) Hall TS (1969) History of general physiology, 2 vols. Univ. Chicago Press, Chicago Hayes JM (1996) The earliest memories of life on earth. Nature 384:2122 Heidenhain M (1894) Neue Untersuchungen ber die Centralkrper und ihre Beziehungen zum Kern und Zellenprotoplasma. Arch Mikroskop Anat 43:423758 Hertwig O (1906) Allgemeine Biologie. Fischer Verlag, Jena Hess B, Boitew A (1971) Oscillatory phenomena in biochemistry. Ann Rev Biochem 40:237258 Hess B, Goldbeter A, Lefever R (1978) Temporal, spatial, and functional order in regulated biochemical and cellular systems.
Naturwissenschaften (2009) 96:123 In: Rice SA (ed) Advances in chemical physics 38. Wiley, New York, pp 363413 Hou L, Luby-Phelps K, Lanni F (1990) Brownian motion of inert tracer macromolecules in polymerized and spontaneously bundled mixtures of actin and filamin. J Cell Biol 110:16451654 Hull DL (1974) Philosophy of biological science. Prentice Hall, Englewood Cliffs, NJ Hulswit M (2006) How causal is downward causation? J Gen Philosophy of Science 36:261287 Islas S, Becerra A, Luisi PL, Lazcano A (2004) Comparative genomics and the gene complement of a minimal cell. Orig Life Evol Bioph 34:243256 Jacob F (1982) The possible and the actual. Pantheon, New York Jacob F (1993) The logic of life. A history of heredity. Princeton University Press, Princeton, NJ Jantsch E (1984) Die Selbstorganisation des Universums. Vom Urknall zum menschlichen Geist. 2. Aufl., Deutscher Taschenbuch Verlag, Mnchen Joyce GF (1987) Cold Spring Harbor Symp Quant Biol 52 Joyce GF, Orgel LE (1986) J Mol Biol 188:433437 Joyce GF, Orgel LE (1993) Prospects for understanding the origin of the RNA world. In: Gesteland RF, Atkins JF (eds) The RNA world. Cold Spring Habor Laboratory Press, New York, pp 125 Kacser H, Burns JA (1979) Molecular democracy: who shares the controls? Biochem Soc Trans 7:11491160 Kant I (1790) Kritik der Urtheilskraft. Lagarde und Friederich, Berlin und Libau (quoted from: Cambridge Edition of the Works of Immanuel Kant, edited by Paul Guyer and Allen W. Wood. Cambridge Univ. Press, Cambridge 1992) Kaplan RW (1972) Der Ursprung des Lebens. Biogenetik, ein Forschungsgebiet heutiger Naturwissenschaft. Georg Thieme, Stuttgart Kaufmann SA (1993) The origin of order: Self-organization and selection in evolution. Oxford University Press, New York Kaufmann S (1996) Even peptides do it. Nature 382:496497 Kay LE (2000) Who wrote the book of life? Stanford Univ. Press, Stanford, CA Kelso JAS, Haken H (1997) Im Organismus sind neue Gesetze zu erwarten. Synergetik von Gehirn und Verhalten. In: Murphy MP, ONeill LAJ (eds) Was ist Leben? Die Zukunft der Biologie. Spektrum Akademischer Verlag, Heidelberg, pp 157182 Kennedy MJ, Reader SL, Swierczynski LM (1994) Preservation records of microorganisms: Evidence of the tenacity of life. Microbiol 140:25132529 Koonin EV, Martin W (2005) On the origin of genomes and cells within inorganic compartments. Trends Genet 21:647654 Koonin EV, Senkevich TG, Dolja VV (2006) The ancient virus world and evolution of cells. Biology Direct 2006:127 Koshland DE (1987) Switches, thresholds and ultrasensitivity. Trends Biochem Sci 12:225229 Kratky KW (1990) Der Paradigmenwechsel von der Fremd- zur Selbstorganisation. In: Kratky KW, Wallner F (eds) Grundprinzipien der Selbstorganisation. Wissensch. Buchgesellschaft, Darmstadt, pp 317 Kuhn TS (1962) The structure of scientific revolutions. Univ. of Chicago Press, Chicago, IL Kuhn H, Waser J (1982) Selbstorganisation der Materie und Evolution frher Formen des Lebens. In: Hoppe W, Lohmann W, Markl H, Ziegler H (eds) Biophysik, 2. Aufl. Springer, Berlin, pp 860905 Kutschera U (2006) Constantin S. Merezhkowsky (18551921) und die Endosymbiontentheorie der Zellevolution. Biologen heute 1:1115 Kutschera U, Niklas KJ (2005) Endosymbiosis, cell evolution, and speciation. Theory Biosci 124:124 Laczano A (1993) In: Bengston S (ed) Early life on earth. Nobel Symposium No. 84, Columbio University Press, pp 5980
Naturwissenschaften (2009) 96:123 Lamarck J de (1815) Histoire naturelle des animaux sans vertebras, vol. 1, Paris Langton CG (1995) Editors introduction. In: Artificial life. An overview. MIT Press, Cambridge, MA Larralde R, Robertson MP, Miller SL (1995) Rates of decomposition of ribose and other sugars: Implications for chemical evolution. Proc Natl Acad Sci USA 92:81588160 Lewes GW (1879) Problems of life and mind. Trubner, London Lowentin RC (1992) The dream of the human genome. The New York Review, pp 3140 Luisi PL (1999) Lipid vesicles as possible intermediates in the origin of life. Curr Opin Colloid Interface Sci 4:3339 Luisi PL, Ferri F, Stano P (2006) Approaches to semi-synthetic minimal cells: a review. Naturwissenschaften 93:113 MacLeod RB (1957) Teleology and theory of human behavior. Science 125:477 Mahner M, Bunge M (1997) Foundation of biophilosophy. Springer, Heidelberg Maier U-G, Hofmann CJB, Sitte P (1996) Die Evolution von Zellen. Naturwissenschaften 83:103112 Mayr E (1979) Evolution und die Vielfalt des Lebens. Springer, Berlin Mill JS (1843) A system of logic. Longmans, Green and Co., London 1859 Miller SL (1953) A production of amino acids under possible primitive earth conditions. Science 117:528529 Mills DR, Petersen RL, Spiegelman S (1967) An extracellular Darwinian experiment with a self-duplicating nucleic acid molecule. Proc Nat Acad Sci USA 58:217 Monod J (1972) Chance and necessity. An Essay on the natural philosophy of modern biology. Vintage books, New York Moreno A, Umerez J (2000) Downward causation at the core of living organization. In: Andersen PB, Emmeche C, Finnemann NO, Christiansen PV (eds) Downward causation: minds, bodies and matter. Aarhus Univ Press, Aarhus, pp 99117 Morowitz HJ (1967) Biological self-replicating systems. Prog Theor Biol 1:3558 Nicholls DG, Ferguson SJ (1992) Bioenergetics. Academic, London Oparin AJ (1924) The origin of life (Russian). Moscow (translated in: Bernal JD (1967) The origin of life. London. Deutsch: Die Entstehung des Lebens auf der Erde. 3. Aufl. Dtsch Verlag der Wissenschaften, Berlin 1957 Oparin AI (1961) Life: its nature, origin and development. Academic, New York Ostwald W (1926) Zur biologischen Grundlegung der Inneren Medizin. Medizinisch-Biologische Schriftenreihe, Heft 1, Radebeul, pp 527 Penzlin H (1987) Das Teleologie-Problem in der Biologie. Biol Rundschau 25:726 Penzlin H (1988) Ordnung- Organisation - Organismus. Zum Verhltnis zwischen Physik und Biologie. Sitzungsber. der Schsischen Akad. d. Wissenschaften zu Leipzig. Math.-Naturwiss. Klasse Bd. 120, Heft 6. Akademie Verlag, Berlin Penzlin H (1993a) Was ist Theoretische Biologie? Biol Zbl 112:100107 Penzlin H (1993b) SelbstorganisationParadigma oder Metapher biologischer Strukturbildung? In: Becker V, Schipperges H (eds) Entropie und Pathogenese. Interdisziplinres Kolloquium der Heidelberger Akademie der Wissenschaften. Springer, Heidelberg, pp 4864 Penzlin H (2002) Warum das Autopoiese-Konzept Maturanas die Organisation lebendiger Systeme unzutreffend beschreibt. Philos Nat 39:6187 Pflger E (1875) Beitrge zur Lehre von der Respiration (1): ber die physiologische Verbrennung in den lebendigen Organismen. Pflgers Archiv 10:251269, 641644
23 Pittendrigh CS (1958) Adaptation, natural selection, and behavior. In: Roe A, Simpson GG (eds) Behavior and evolution. Yale Univ. Press, New Haven, pp 390416 Pittendrigh CS (1993) Temporal organization: Reflection of a Darwinian clock-watcher. Ann Rev Physiol 55:1754 Polanyi M (1968) Lifes irreducible structure. Science 160:1308 1312 Prigogine I (1947) Etude thermodynamique des Phenomenes Irreversibles. Desoer, Liege Riedl R (1981) Biologie der Erkenntnis. Die stammesgeschichtlichen Grundlagen der Vernunft. 3. Aufl. Paul Parey, Berlin, Hamburg Rosen R (ed) (1985) Theoretical biology and complexity. Three assays on the natural philosophy of complex systems. Academic Press Inc. Orlando, London Rosen R (1991) Life itself: a comprehensive inquiry into the nature, origin and fabrication of life. Columbia University Press, New York Roux W (1895) Der zchtende Kampf der Theile oder die Theilauslese im Organismus. V. Cap. Ueber das Wesen des Organischen. Gesammelte Abhandlungen ber Entwicklungsmechanik der Organismen. 1. Band. Wilhelm Engelmann, Leipzig, pp 387416 Rual JF et al (2005) Towards a proteome scale map of the human protein-protein interaction network. Nature 437:11731178 Russell ES (1945) The directiveness of organic activities. Cambridge University Press, Cambridge Sabater B (2006) Are organisms committed to lower their rates of entropy production? Biosystems 83:1017 Schrdinger E (1944) What is life? Cambridge University Press, Cambridge Schwartz RM, Daydoff MO (1978) Origins of prokaryotes, eukaryotes, mitochondria, and chloroplasts. Science 199:395403 Shimkets LJ (1998) Structure and sizes of genomes of the Archaea and Bacteria. In: Bruijn FJ de, Lupskin JR, Weinstock GM (eds) Bacterial genomes: physical structure and analysis. Kluwer, Boston, MA, pp 511 Simpson GG (1963) Biology and the nature of science. Science 139:8188 Srere DA (1993) Wandering (wonderings) in metabolism. Biol Chem 374:833842 Stelzl U et al (2005) A human proteinprotein interaction network: a source for annotating the proteome. Cell 122:957968 Storch V, Welsch U (2005) Kurzes Lehrbuch der Zoologie. 8. Aufl. Elsevier GmbH, Mnchen Thorpe WH (1978) Purpose in the world of chance. Oxford University Press, Oxford Uexkll JV (1928) Theoretische Biologie. 2. Aufl. Springer, Berlin Van Gulick R (1993) Who is in change here? And whos doing all the work? In: Heil J, Mele A (eds) Mental causation. Oxford Univ Press, Oxford, pp 233256 Verworn M (1903) Die Biogenhypothese. Fischer Verlag, Jena Vreeland RH, Rosenzweig WD, Powers DW (2000) Isolation of a 250 million-years-old halotolerant bacterium from a primary salt crystal. Nature 407:897900 Wchterhuser G (1988) Before enzyme and templates: theory of surface metabolism. Microbiol Rev 52:452484 Weismann A (1892) Das Keimplasmaeine Theorie der Vererbung. Gustav Fischer, Jena Wicken JS (1987) Evolution, thermodynamics, and information. Oxford Univ. Press, New York Woese CR (2000) Interpreting the universal phylogenetic tree. Proc Natl Acad Sci USA 97:83928396 Zhaxybayeva O, Lapierre P, Gogarten JP (2005) Ancient gene duplications and the root(s) of the tree of life. Protoplasma 227:5364

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The riddle of life, a biologists critical view

Naturwissenschaften (2009) 96:123

Naturwissenschaften (2009) 96:123

Naturwissenschaften (2009) 96:123

Naturwissenschaften (2009) 96:123

Naturwissenschaften (2009) 96:123

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Naturwissenschaften (2009) 96:123

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Fig. 7 Radiolaria (after Ernst Haeckel)

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