The uncertainty principle as an evolutionary engine

BioSystems, 27 (1992) 6 3 -

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Elsevier Scientific Publishers Ireland Ltd.

The Uncertainty Principle as an evolutionary engine Koichiro Matsuno Department of BioEngineering, Nagaoka University of Technology, Nagaoka 940-21 (Japan) (Received November 13th, 1991) (Revision received June 10th, 1992)

Heisenberg's uncertainty principle in quantum mechanics underlies the genesis of evolutionary variability. When the uncertainty principle is coupled with the incontrovertible principle of the conservation of energy and material resources, there appears an uncertainty relationship between local fluctuations in the quantities to be conserved on a global scale and the rate of their local variation. Since the local fluctuations are accompanied by the non-vanishingrate of variation because of the uncertainty relationship, they generate subsequent fluctuations. Generativity latent in the uncertainty relationship is non-random and ubiquitous all through various evolutionary stages from abiotic synthesis of monomers and polymers up to the emergence of behavior-induced variability of organisms.

Keywords: Evolution; Genotype; Natural selection; Phenotype; Uncertainty principle; Variations. 1. Introduction

Evolution cannot proceed without generating its own changes. The ubiquity of evolutionary variability has provided us with a wide variety of views on how variations are generated and acted upon in evolution. One of the popular views has been the neo-Darwinian one, such that natural selection comes to act upon random variants that have been generated independently of the selection process, as expressed in the frequently quoted dictum of the natural selection of random variants. Implicit in this dictum is the presence of the law of 'higgledy piggledy' to be applied to the genesis of random variants (Palladino, 1990). However, whether natural selection is separated from generating variations is not a matter simply of the viewpoint one may take, but a serious question that has to be addressed (LOvtrup, 1987; Stebbins, 1987; Matsuno, 1988). Correspondence to: Koichiro Matsuno, Department of BioEngineering, Nagaoka Nagaoka 940-21, Japan.

University of Technology,

If the neo-Darwinian separation between natural selection and variations is taken literally, the variants generated would be random by definition, in the sense that they do not anticipate what natural selection would fix at a later time. The neo-Darwinian theory of natural selection is an extremal theory that treats individuals appearing in the domain as behaving in such an manner as to maximize or minimize the values of certain variables (Rosenberg, 1985; Travis, 1989). This theory presumes that variations are generated first and then acted upon by natural selection as an agent of seeking optimality. Neo-Darwinian natural selection thus reduces to natural selection acting upon the products that have already been made. The presumed temporal sequence of variants followed by natural selection, however, raises a serious difficulty when we let the two processes, generating variations and natural selection, be concurrent. The unattainability of concurrency would render natural selection as a process extremely difficult, since the process of natural selection is prohibited from acting while the genesis of variations is going on. Neo-Darwinian

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64 natural selection perforce eliminates natural selection in progress simply by restricting itself to the natural selection of products. Unless the two processes of natural selection and generation of variations alternate with each other in sequence, neo-Darwinian natural selection could not be possible. The matter of how both natural selection and generation of variations can coexist with each other will be settled only by eliminating the arbitrary stipulation of a forced separation between the two processes. Natural selection in the broadest sense refers to a process in progress. Similarly, generating variations also refers to a process in progress. This concurrency makes it the rule, not the exception, for natural selection to remain inseparable from generating variations. Variability turns out to be a common denominator of both natural selection as a process and generation of variations. We shall in this article try to trace and demonstrate how variability could evolve in time, from the primitive stage of the abiotic synthesis of monomers and polymers up to the emergence of the biologically full-blown mechanism of maintaining both phenotypic and genotypic variability. Emphasis will be placed on calling attention to the uncertainty principle, originally conceived in quantum mechanics, that would turn out to serve as a synchronic commonality underlying the generation of variability in evolution.

2. Variability The neo-Darwinian dichotomy between natural selection and generation of variations certainly has provided a major problem encountered in evolutionary process with a solution of a scientific nature. The actual solution has a form such that the problem inviting its own solution has been successfully isolated from other problems in such a manner that the solution does not question everything (Gayon, 1990). In contrast, problems of a philosophical nature allow an indefinite sequence of all sorts of related questions which require in advance the adoption of a position on the totality of reality.

Neo-Darwinian natural selection thus prohibits us from speaking about natural selection in progress. In addition, it also prohibits from asking the natural selection to speak about because of the imposed isolation from generating variations (Grene, 1990). An exit from this confusion surrounding the concept of natural selection is not to refer to it explicitly, but rather to pay attention directly to the variability that underlies natural selection. One of the earliest form of variability in evolutionary process is the abiotic synthesis of monomers and polymers.

2.1 Abiotic synthesis of monomers and polymers Simulated experiments on the abiotic synthesis of monomers such as amino acids from a reducing atmosphere suggests that when the energy is supplied in the form of an electric discharge, the amino acids are formed not directly from those elements as methane, ammonia and water, but from the solution reactions of intermediates such as hydrogen cyanide and aldehyde (Miller and Orgel, 1974). The presence of the intermediates in the synthesis is in accord with the general trend of evolution such that one interaction sets the stage for subsequent interactions and these for the next and so on (Hall, 1990). The previous interaction functions as an endogenously generated initialboundary condition for the subsequent interaction. The succession of interactions proceeds both irreversibly and non-randomly in the sense that only those interactions that can satisfy the condition of both material and energy resource limitation a posteriori could be realizable at any point in sequence. There are many possibilities in anticipation, but only one definite sequence of events in retrospect. The synthesis of hydrogen cyanide and aldehyde from methane, ammonia and water, for instance, points to the emergence of the stage of an intermediate interaction that fulfills the conditions of both material and energy resource limitations at least over the initial period of the reactions that end up producing amino acids. Variability as a measure of the multitude of

65 possible interactions is in itself varied as the free mixture of methane, ammonia and water is transformed into that of hydrogen cyanide and aldehyde. In the latter the direct pathway from methane, ammonia and water to amino acids has already been eliminated. Of course, intrinsic variability associated with amino acids can be seen in thermal heterocopolymerization of amino acids, or what Fox (1984) calls the selfsequencing of amino acids. Consider, for instance, the tripeptide synthesis due to thermal polymerization of the three amino acids, glutamic acid, glycine and tyrosine, in a simulated primordial soup (Nakashima et al, 1977; Hartmann et al, 1981). It has been observed that the identifiable sequences are restricted only to pyroglutamyltyrosylglycine (
distinguish between the two. Indefiniteness about the separation between behaving as a reactant and joining in the endogenous boundary condition persists as long as the concerned monomer or polymer survives. In fact, this form of indefiniteness provides a surviving polymer with the further capacity of variability. Only those material aggregates that succeed in taking in necessary material resources to the extent allowed by the previous variability survive as carriers of further variability. Evolutionary variability thus becomes increasingly constrained with time as eliminating variabilities inherent to unsuccessful resource exploitation. A more constrained form of variability can be seen in genic variations that appear at a later stage of evolution. 2.2 Transversal and transitional mutations in pseudogenes One particular process of generating variations in the realm of full-blown biology is found within point mutations as demonstrated in nucleotide substitutions in DNA molecules. Spontaneous point mutation means a substitution of one of the four nucelotides, adenine (A), cytosine (C), guanine (G) and thymine (T), by one of the remaining three. Since A is complementary to T and G to C in the double-strand structure of DNA, one can identify the consequence of mutation by referring only to the sense strand, i.e., the untranscribed strand. Thus, an A-G substitution, denoting an A base in the sense strand being replaced by G, naturally induces a substitution of T by C in the complementary strand because of the base complementarity. An A:T pair in the double-stranded DNA molecule is replaced by a G:C pair if point mutation A - G occurs on the sense strand. Likewise, mutation A - T induces a substitution of pair A:T by T:A and so on. A suitable candidate for measuring the effect of spontaneous point mutations is pseudogenes such as goat pseudogenes (Gojobori, Li and Graur, 1982). The use of pseudogenes is due to the fact that they are apparently subject to no functional constraints in connection with

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proteins so that the pattern of nucleotide substitution preserves the pattern of spontaneous point mutation. Their selective neutrality guarantees that none of the mutations that could occur in these pseudogenes would have been subject to selection (Kimura, 1968, 1983; King and Jukes, 1969). The pattern of spontaneous point mutation is identified by measuring the difference between two closely related pseudogenes derived from a common ancestral pseudogene, neglecting the possible multiple substitutions of simultaneous nature compared with a single substitution because of their probabilistic unlikelihood. Point mutations of twelve different members (A - C, A ~ G,..., T - G) are classified into the two groups, transitional and transversal. The transitional mutations include the four types of A - G, G - A, T - C and C - T and the transversal mutations include the remaining eight possibilities. If spontaneous point mutation is random among the 12 different types, the relative frequency of transitional mutation would be 33% (4/12) because of the equal likelihood of each mutation. The pattern of these random mutations would preserve its symmetry property in the sense that the uniform pattern of random mutations remains invariant with time. The measured reality, however, does not conform with the hypothetical symmetry based upon random mutation. The study of two closely related pseudogenes evolved from a common ancestral one reveals the relative frequency of transitional mutation is 59.2%, almost twice as high as the value of 33% that would be expected from the assumption of random mutation (Li, Wu and Luo, 1984). The relative frequency with which either C or a is replaced by any of the three others is found almost twice as much as that for A or T to be replaced by the other nucleotides, indicating that C and G are more likely to be replaced than A and T. Genic variability of point mutations is thus shown to be non-uniform among A, T, G and C, at least for pseudogenes. The non-uniformity of genic variability is a consequence of applying a certain constraint upon a hypothetically uniform and random variability. Such an unevenness

witnesses that the endogenous boundary con(~ition upon each type of point mutation and the mutation dynamics under this condition differ among A, T, G and C. Indefiniteness about the separability between the mutation dynamics and the endogenous boundary condition upon them can be further elucidated by controlling the boundary condition, though of course only to a limited extent. 2.3 Stress-induced mutations Mutations in general and point mutations in particular, have been widely believed to arise randomly and uniformly without any reference to their utility. The classical experiments on mutations to phage resistance of Escherichia coli confirmed that at least some forms of bacterial mutation are occurring spontaneously before the bacteria can detect any indication of their possible later utility, if any. In particular, mutations to phage resistance are not expressed in the phenotypic domain until several generations after the mutations have occurred. This time-lag between the occurrence of mutations and their expression in the phenotype suggests two possibilities. One is that mutations could be random and the environment right after the mutations have occurred is responsible for determining which survive and the other is that mutations themselves could be non-random and possibly product-oriented. The overwhelming choice out of the two possible interpretations has been for random mutations. Nevertheless, the choice has to be done by minimizing interference from untested theoretical premises. What is wanted in this regard is to contrive an experiment in which mutations are immediately expressed in the phenotypic domain. Confronting the pressing need for designing an ingenious experiment so that phenotypic expression may immediately follow the process of mutation, Cairns, Overbaugh and Miller (1988) found that the formation of papillae of lactosefermenting mutations from non-fermenting strains of E. coli plated on media containing lactose starts as soon as the mutation occurs. The particular strain they investigate is due to Shapiro (1984) such that the positive regulatory

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element controlling the arabinose operon araC is placed upstream of the lactose operon lacZ but separated from it by a short segment of Mu bacteriophage DNA that contains transcription terminating signals. This articulated strain lacks both the arabinose and the lactose operons and yields a phenotypic expression Ara- and Lac-, denoting that the strain lacks both arabinose and lactose activities. It cannot grow on either arabinose or lactose. However, if a mutation deleting the intervening Mu segment occurs, a new phenotype Lac(Ara) ÷ will appear which is able to grow on lactose provided that arabinose is present (Shapiro, 1984). Cairns et al. (1988) studied the spontaneous appearance of Lac(Ara) ÷ cells under several different conditions from the strain Lac- • Ara- cells, which cannot grow on either arabinose or lactose. Their results are summarized as follows. In rich media containing both lactose and arabinose, large numbers of Lac(Ara) ÷ cells start to appear after 3 - 4 days at 30°C, where the proportion of L a c - ' A r a cells that are becoming Lac(Ara) ÷ must be at least 10 -s. In rich media without lactose or without arabinose, on the other hand, Lac(Ara) + cells do not accumulate at a detectable rate. In contrast, when lactose is added to a stationary culture that has arabinose but not lactose, Lac(Ara) ÷ cell must appear within 1 - 2 h of the addition of lactose. The spontaneous appearance of mutant cells Lac(Ara) ÷ at an extraordinarily large rate suggests that when the original strain Lac- • Arais placed under the stressed condition lacking necessary nutrients, mutations that allow the mutants to survive and to grow there can be enhanced and even that bacteria may seem to choose which mutations they should produce. This observation supports the idea that resource exploitation in the phenotypic domain can alter genic variability at least so that the organism may be able to examine their extensive armory of resource exploitation strategies to meet the demand for their sustenance and possibly growth (Condit, 1990). Those that failed in resource exploitation cannot survive or grow. The stressed condition implies that the external environment is becoming less resourceful and

the organism as a material carrier of resource exploitation is put under the more pressing need for revising its strategy for getting necessary resources in order to maintain itself. Although the phrase 'resource exploitation to maintain itself' may sound teleological, it simply points to the obvious fact that the surviving organism is no more than a carrier of various metabolic activities. Any autonomous aggregate open to material flow through its metabolism adjusts its interaction within itself and with its outside endogenously at least so as to make both ends of material inflow and outflow meet. Resource exploitation by an organism is just one form of interaction adjustment for maintaining its metabolic activity or fulfilling material flow continuity in an open material aggregate. The less resource-rich the environmental condition becomes, the more frequently the strategy for resource exploitation has to be revised and tried so as to make both ends meet. This is just one mode of fulfilling the condition of material flow continuity at the location of the surviving organism. When an organism is suddenly placed under stressed conditions, it can react either actively by revising the previous strategy in an endogenous manner or passively simply by following the previous one. Revising strategies for resource exploitation more frequently upon facing stressed conditions is certainly a reactively active possibility for fulfilling material flow continuity in an organism. Stress-induced mutations, even if they seem to be product-oriented, are thus in accord with physical principles of material flow continuity. Stress-induced mutations are not limited to bacteria. The occurrence of certain genetic events is accelerated under conditions of environmental stress (Jackson, 1991). Many types of stress appear to produce the molecular effect of intensive modification of DNA bases. The frequency of generating molecular lesions under stress may far exceed the usual mechanisms of repair and restoration. The excision repair of DNA damages in the gap-related opposite sites of both strands seems to trigger an unexpected high rate of recombination and point mutation

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(Salganik, 1987). In particular, as the rate of genetic recombination increases, the potential for mutation increases substantially as we observed in bacteria and the number of mobile or transferable genetic elements increases (Belyaev and Borodin, 1982; Zhuckenoko, Korol and Kovtyukh, 1985; Borodin, 1987; McClintock, 1984). Genic variability can be variable against environmental stress. This does not necessarily imply that stress-induced mutations are of nonbiological origin, though most of them actualized in experiments are artifacts. The behavior of an organism, which is certainly of biological origin, constitutes an element of the environment or environmental stress to others. Evolutionary variability would remain inadequate unless behavioral components are taken into account.

2.4 Behavior-induced variability Once behavior is allowed to affect evolutionary variability, its relationship with both genotype and phenotype would become far more complex than otherwise. Selective behavior for properties as a mode of evolutionary variability is totally different from selection or sorting of individual things (Sober, 1984). However, selection for properties as a causal process, the effect of which is a sorting, remains opportunistic (Kauffman, 1985). In fact, selection does not proceed with precision on a complex diagram of regulation, nor does it provide more than indefinite constraints which impose limitations, such as material flow continuity, on its possible action. Still, evolution is seen as changes in the frequencies of behavioral strategies rather than, for example, alleles or genotypes (Mitchell and Valone, 1990). The possible co-existence of both opportunistic selection for properties and behavioral strategies allows the latter to be degenerate with respect to future strategies to come. The generativity of behavioral strategies yet to come by way of dissolving the degeneracy latent in preceding ones can produce synthetic and innovative formulations that are not reducible to pre-given ones (Dannefer and Perlmutter, 1990). Individual organisms are constituted and

further transformed as part of a collection of organisms, while this world of organisms is itself a product of each organism's activity. There is in fact, a causative relationship from behavior to genotype. For example, the phenomenon of cyclomorphosis points to epigenetic information for development coming from outside the organism, in which a chemical released by a predator evokes a morphological change in the offspring of a prey species by switching development into new morphogenetic and differentiative pathways (Hall, 1990). The observed morphological variations could have been genetically assimilated in evolution (Waddington, 1975; Vancassel, 1990). In other words, the potential for such variation was present in the original population, but only rarely expressed under stress, and was therefore purely phenotypic. However, at the other end of the process, the potential for morphological variation is nearly always expressed because the selective behavior for a certain trait can finally alter the genetic make-up of the population. This appraisal of genetic assimilation is supportable even if we admit Weismann's principle stating that the environment cannot affect the genes transmitted by an organism. In particular, what is affected by the environment is not the gene itself, but the population gene pool. Behavioral flexibility is probably basic to evolutionary process especially from the viewpoint that phenotypic and genotypic variability tends to be high under conditions of severe physical and biological stress, particularly for those behaviors important in determining survival (Mayr, 1970). Following a similar line of argument, one can also observe that behavior may play an important role in the process of speciation (Hoy, 1990). Of course, the gradual accumulation of genetic changes during phyletic evolution is a well established phenomenon and substantial allozymic divergence has been found to be associated with speciation events (Mindell, Site and Graur, 1990). What is emphasized here in relation to speciation, however, is the primacy of behavioral plasticity. Sexual selection is in fact a particular

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example pointing to the significance of behavioral plasticity or flexibility in the process of speciation (Hoy, 1990; Stearns, 1990). Sexual selection is a selection for properties and is accordingly opportunistic. Preceding behavior involved in sexual selection sets the stage for subsequent behavior and that for the next and so on, as in the case of interaction in general. Each behavior is opportunistic, but is constrained by resource limitation such that there is neither sources nor sinks for energy. This sequence of opportunistic behaviors under inevitable resource limitation can irreversibly change the corresponding population gene pool and lead to speciation as a consequence. Speciation through sexual selection may arise through the action of opportunistic or generic behaviors. Subsequent evolution of genetic mechanisms would only stabilize and refine speciational outcomes originally guided by generic behaviors merely as a means of evolutionary bookkeeping (Wimsatt, 1980) in terms of genes such that environmental stress induces a re-organization of genetic make-up. In fact, stress-induced mutations are an extreme case of behavior-induced variability in that the behavior of some organisms causes stress to others. Behavior is opportunistic because of the indefiniteness latent in the constraints that any behavior has to conform to, such as the condition of material flow continuity. However, it should be emphasized that such phenotypic plasticity is by no means prohibited from influencing genes and genotypes. The genotype is also plastic through the reorganization of genetic make-up initiated by opportunistic behaviors. This form of behavior-induced genetic variability is distinguished from the defunct principle of the inheritance of acquired traits in spite of the apparent resemblance. If the influence from acquired behavior to genetic make-up were claimed to be unique, that sort of a Lamarckian assertion could easily be refuted by recalling the Weismannian separation between somatic behaviors and germ-cell lines. What counts in the pathway from behavior to gene or genotype is the lack of the one-to-one correspondence between the two. Behavior does

not determine what specific genetic make-up will follow. Instead, it induces changes in genic variability as exemplified in the stress-induced acceleration of the reshuffling of genes. Varied genic variability is to be inherited through behavior. Furthermore, behavior in itself is plastic enough not to be totally controlled by the underlying genotype, while the former is placed under the influence of the latter. Genic variability is kept constantly varying through behavior. This indefinite repercussion between behavior and gene gives rise to the inheritance of acquired variability instead of acquired traits. An acquired variability in genes further influences the extent of plasticity in the behaviors to follow. And again, the following behavior can induce further changes in genic variability. This sequence from behavioral plasticity to genic variability and back can continue indefinitely. Lamarckian inheritance of acquired traits identified as acquired things is misconceived in discarding the potential capacity of those behavioral traits yet to be acquired. If Lamarckian inheritance were taken at its face value, organisms would reduce to miserable victims of an unmerciful environment. On the other hand, if what is inherited is a form of generativity instead of an already generated pattern of behavior, the carrying organism can maintain its own potential capacity not to be controlled in its entirety by the environment. The room for genes and genotypes that serves as a vehicle for keeping a certain independence from the environment, of course within a limited extent, is in the fact guaranteed by the indefinite generativity or variability induced by behaviors. Conversely, genes and genotypes cannot specify the behavior of organisms uniquely even if the environment acting upon the latter were completely specifiable. If the pathway from gene to behavior under an identifiable environment were unique, behavior-induced variability would eventually be exhausted. This is because behavior in the present framework would be a configuration to be determined by both genotype and the environment. Although the strictly one-way influence from gene to behavior conceived in the neo-Darwinan scheme can give

70 rise to phenotypic plasticity in the sense that the genotype induces various phenotypic expressions responding to variations in the environment, this variability in the phenotype would totally depend on how the environment acts. Furthermore, by letting the environment be the sole cause of inducing mutations in genes, the neo-Darwinian view renders genes miserable victims of an unmerciful environment, as are organisms conceived within the Lamarckian framework. Both the neo-Darwinian and the Lamarckian pathways impose the traffic regulations that are totally incompatible with each other while yet sharing the same road leaving the environment untouched. Once it is recognized that a major constituent of the environment is other individual organisms and effects of genes (Taylor, 1987), the environment that can influence but cannot be influenced by the organisms and genes residing there would no longer be tenable. Both the Lamarckian inheritance of acquired traits and the neo-Darwinian primacy of genes, though totally opposite in their claims, suffer from the common inadequacy in letting the environment be the only active player on the evolutionary stage. Appraisal of the generativity on the part of individual organisms is a way out of such a completely articulated stipulation. Genic generativity or variability also follows because genes are carried by individual organisms. In this regard, the neo-Lamarckian inheritance of acquired variability can overcome both the Lamarckian inheritance of acquired traits and the neo-Darwinian primacy of genes in that those organisms carrying the acquired variability or generativity are active in transforming possibilities into the actual. The inheritance of acquired variability derived from behavior-induced variability in genes is certainly physical (Goodwin, 1984) because it takes place in three-dimensional physical space. The underlying physical mechanisms are plastic or generic enough including adhesion, surface tension and gravitational effects, viscosity, phase separation, convection and reactiondiffusion coupling. In particular, major morphological reorganizations in phylogenetic

lineages may arise by the action of these generic physical mechanisms on developing embryos (Newman and Comper, 1990). Subsequent evolution of the genetic apparatus could stabilize developmental outcomes originally guided by physical mechanisms which are plastic enough to influence one another themselves (Johnston and Gottlieb, 1990). Genic variability is no more than a part of generic physical processes that proceed in both the morphological and behavioral domains (Dietz, Burns and Buttel, 1990). We thus come to face a more specific problem of how generic physical mechanisms could maintain and transform their own variability.

3. The Uncertainty Principle Organisms constantly detect their own need for taking in necessary material resources. This process is a means of fulfilling the condition of material flow continuity in open material aggregates, since any organism is no more than an instance of an aggregate open to material flow through its metabolic function. Realization of material flow continuity in any arbitrary organism allows it to be an agent for both detecting and implementing the condition of continuity internally, or an agent of internal measurement (Matsuno, 1985, 1989). Internal measurement inherent to organisms is responsible for maintaining the continuity of material flow there. In order to see the dynamics underlying internal measurement, let us suppose that the material flow of a certain molecular species measured and taken in by an organism is f. The internal measurement of the intensity of the molecular flow rate certainly takes time, so let us also suppose that the time interval necessary for measuring and fixing the flow intensity is At. If variations occur in the flow intensity through the process of internal measurement and give rise to fluctuations by the amount of ~f, it will be self-evident that fluctuations ~fcome to actualize over the time interval At. Consequently, if one further defines the rate of variation in fluctuations 6f by using the

71 symbol of their time derivative 5~ a simple relationship 5 f ~ ~fAt will follow. The literal implication of this relationship is that if the intensity of the fluctuating quantity measured over the time interval At is ~f, then the average rate ~¢ of variations in the fluctuating quantity would reduce to ~f/ht. However, the important implication is more than this. Determination of either one of fluctuations ~f or the rate of their variations ~:f places a certain limit on the other's value range. How macroscopic or microscopic these quantities would be depends upon what is taken as a means of measurement. Above all, both the fluctuation intensity and its rate of variation cannot be determined simultaneously. There exists a certain indeterminate and indefinite relationship between these two quantities. If one introduces the normalized fluctuation rate hi -- 5"flSf, the uncertainty relationship 5f -- 5~¢Atis rewritten to hi At ~ 1 What is unique to the uncertainty relationship is that fluctuations imputed to the process of internal measurement for detecting and implementing the condition of material flow continuity subsequently induce similar fluctuations. This is due to the fact that the rate of variation in fluctuations is nonvanishing. This nonvanishing rate of variation in the material flow in a local region disturbs the current condition for material flow continuity in the neighborhood. The uncertainty relationship shows that internal measurement necessary for material flow continuity serves as a generator of fluctuations or variations. Of course, the uncertainty relationship due to internal measurement and the incontrovertible physical principle of conservation maintains an intimate relatedness with Heisenberg's uncertainty principle. The uncertainty principle with regard to the measurement of energy is written as hE At = l~, where AE denotes the extent of

the uncertainty in externally measuring the energy E of the system under consideration over the time interval At and h, is Planck's constant divided by 2v. The physical origin of the uncertainty principle is in measurement and the measurement originally conceived by Heisenberg took the incorporation of measurement apparatus provided externally for granted. Even if the energy to be measured may seem to violate the empirically incontrovertible principle of the conservation of energy, the uncertainty in the measured energy by the amount of hE is no more than a contribution from the measurement apparatus which remains external to the system to be measured. The measurement apparatus can be deemed to be a source of energy that gives rise to the uncertainty in the amount of energy to be measured. On the other hand, however, if internal measurement is taken into account, Heisenberg's uncertainty principle must be interpreted in a completely new fashion. It is no longer tenable to assume that measurement would cause a superficial violation of the physical principle of the conservation of energy that was permissible in the framework of external measurement. Internal measurement underlying and entailed by the principle of the conservation of energy can create fluctuations in the energy by the amount of ~e in a local region over the same time interval At. The uncertainty principle unquestionably imposes such a constraint as ~te At -~ h upon the process of internal measurement. In addition, energy fluctuations ~e also vary in time with the rate ~'e ~ ~e/ht because of the involvement of mutually interfering internal measurement on the conservation of energy. The normalized fluctuation rate of energy Ai /t'e/Se certainly satisfies the uncertainty relationship Ai At ~ 1. Heisenberg's uncertainty principle within the framework of internal measurement points to the fact that the empirically incontrovertible principle of the conservation of energy, for instance, induces indefinite repercussions of internal action for fulfilling the principle locally (Conrad, 1989; Matsuno, 1989). Fundamental to the operation of the -

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uncertainty principle is generation of variations or fluctuations in those quantities that are conserved on a global scale. Biological organisms are certainly agents of detecting and fulfilling the need for material resources that are undoubtedly conserved on a global scale. Resource exploitation by each individual organism is generative in exploring the necessary material resources because of the uncertainty relationship between fluctuations in the resource flow taken in by the organism and the rate of their variations. Perpetual fluctuations originating in the uncertainty relationship in each organism may function as a generator of novelty while equilibrating the disparity between what the organism intends to get and what it has actually got. Equilibration of resource flow in each organism, however, subsequently causes in others a renewed disparity or disequilibrium between the intended and accomplished through the interface of intervening organisms (Gunji, 1991). Equilibration is thus perpetuated by rendering the elimination of flow disequilibrium by one organism constantly a cause of disequilibria to be eliminated subsequently by others. There really is no, nor has there every really been any, stable equilibrium (Dator, 1990). The consequence of equilibration is the observation of resource flow continuity, while there is no material means for foretelling how equilibration would proceed in a specific manner. It is physically impossible to tell what is currently going on at separate places in a simultaneous manner. Nothing can be detected or identified unless a corresponding signal arrives. This distinction between the indefiniteness in anticipation and the definiteness in the record is the source of novelty latent in the generativity unique to the uncertainty relationship. The uncertainty principle in general, or the uncertainty relationship between fluctuations in the quantity to be conserved on a global scale and the rate of their variation in particular, is a fundamental characteristic of physical interactions expressed in terms of internal measurement. The process of measurement is necessary

for generation of fluctuations ascribed to the uncertainty principle, though the principle itself remains uncommitted as to how measurement would proceed. External measurement by means of a measurement apparatus provided externally is at most intermittent depending upon how the experimenter would like to control the apparatus, while internal measurement is continuous. As a matter of fact, internal measurement in each organism for locally detecting and upholding flow continuity of the quantity to be conserved on a global scale does induce similar internal measurements in the neighborhood in a successive manner. Successive spill over of equilibration accompanied by internal measurement never stops. The uncertainty relationship between fluctuations and the rate of their variation exhibits a sharp contrast to the uncertainty principle of Heisenberg in that any interacting body can serve as a measuring agent as much as any organism detects and acts upon others. Internal measurement converts the uncertainty principle of Heisenberg to an engine for generating de novo variations. Behavior-induced variability is just an instance illustrating that non-exhaustive generativity inherent to the uncertainty relationship between fluctuations and the rate of their variation applies to a group of interacting organisms. Any variation in the behavior of interacting organisms generates an indefinite repercussion of varying the manner in which material resources may be taken in by each organism (Dobzhansky, 1969; Salthe, 1985). Behavior-induced variability is thus understood to be a mode of the uncertainty relationship between fluctuations in the material resource flow and the rate of their variation, operating in the manner of resource exploitation among interacting organisms. The possibility that the uncertainty relationship in terms of resource flow among organisms may induce variations in the genetic make-up of some of the organism is not excluded, since genic variations can cause the organism to change the manner of resource exploitation.

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The indefinitely continuous operation of the uncertainty relationship is of course not restricted solely to interacting organisms. Inside an organism those units such as organelles and organs can serve as agents of internal measurement. Intra-organismic internal measurement makes the uncertainty relationship to be a generator of variations, including the reshuffling of genetic make-up. We suggest that stress-induced mutation is just an instance of the generativity inherent to the uncertainty relationship proceeding through intraorganismic internal measurement. In fact, the abiotic synthesis of monomers and polymers is a form of the uncertainty relationship between fluctuations in the incoming atomic and molecular flow and the rate of their variation at least in the period over which material aggregation occurs. Such abiotic syntheses means that even a molecule or a molecular aggregate serves as an agent of internal measurement. Any material aggregate open to material flow is part of the process of detecting and implementing the condition of material flow continuity. Molecules and molecular aggregates are no exception in exercising the capacity of setting and resetting their interaction with others so as to fulfill material flow continuity and thus render themselves agents just as organisms and their constituent organelles and organs are. The uncertainty relationship between local fluctuations in any quantity to be conserved on a global scale and the rate of their variation thus serves as a connecting thread all through the various stages of material evolution. Underlying the generativity or variability inherent to the uncertainty relationship is an internal measurement that is capable of detecting and then acting upon others. For biological organisms, this process of internal measurement is evident because of the biological functions they undertake, such as sensing and reacting. But, the capacity of internal measurement is not limited to biological organisms. Once it is admitted that any change in interaction propagates in a medium at a finite velocity, equal to or in most cases less than light velocity,

it becomes inevitable to have a dichotomy between before and after detecting the signal originating somewhere. There is no material means to detect what signal will arrive before it has actually arrived. The asymmetry between the prior uncertainty and the posterior certainty latent in material interaction thus makes any interacting body an agent for internally detecting and then reacting upon the others (Montogomery, 1990) at least in the manner of fulfilling the incontrovertible physical principle of conservation. The uncertainty relationship between local fluctuations in the quantity to be conserved on a global scale and the rate of their variation, or Heisenberg's uncertainty principle within the framework of internal measurement, serves as an evolutionary engine because of its continuous generativity and variability.

4. Evolutionary engine It has been well established that natural selection underlies evolutionary process and there is no argument about empirical evidence showing how natural selection has functioned in the record. Nonetheless, there is no material means for predicting what natural selection will bring about in the future. The dichotomy between the prior indefiniteness and posterior definiteness is latent in natural selection. If one understood natural selection as the process of selection of products, the reference standard for determining which products should be selected would have to be explicit beforehand. The asymmetry between before and after the selection of products would disappear. In fact, neo-Darwinian natural selection expressible in terms of the selective value of a gene is a representative case of the selection of products, irrespective of whether the selective value would finally reduce to be vanishingly small as in the neutral hypothesis (Kimura, 1983). However, the selection of products clearly differs from the selection for properties or traits (Sober, 1984). Darwinian natural selection has justifiably been introduced as a mode of the selection for properties (Matsuno, 1988).

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Properties in general are an attribute of temporal development of the entities under consideration. The properties of organisms are also the outcome of natural selection. This convoluted relationship between natural selection and properties make each one of them indefinite in its implication. Only when, in the time interval required for defining a property, it remains fixed, can one associate the representation of such a property with a product obtainable over the same period. Selection for the property could then reduce to the selection of a product in which all of the aspects originating in the property can be traced. Unless such an articulation of limiting the time interval for defining properties is taken, natural selection yet to come remains indefinite and opportunistic (Johnson, 1990). There is an obvious asymmetry between natural selection in anticipation and natural selection in the record, since what seems to be an opportunistic commitment can be identified only after it has occurred. Natural selection as a form of material interaction thus reduces to a mode of internal measurement that allows in itself the dichotomy between the prior indefiniteness and the posterior definiteness. What supports natural selection turns out to be internal measurement, since the agents of internal measurement are ubiquitous in material interaction. Every interacting molecule is participating in internal measurement in the sense that the molecule cannot detect what is going on in other molecules in a simultaneous manner. It is only after a signal originating in the other molecules has arrived that a molecule can measure what happened there, though in a way so as to preserve the incontrovertible principles for the conservation of various quantities. An interacting molecule as the agent of internal measurement thus fulfills at least one of the necessary conditions for becoming an agent of natural selection, though of course not a sufficient condition. It is this perspective which makes it possible for abiotic synthesis of monomers and polymers to yield an evolutionary forerunner of the biologically fullblown operation of natural selection. A common agent of internal measurement en-

countered in the biological realm is the individual organism. It is the organism which senses and then reacts upon other organisms. Still, genes in the individual organism can also serves as the agents of internal measurement in the same sense as interacting molecules do. Both genes and individual organisms function as the agents of natural selection, though in an opportunistic manner. This indifference between genes and individual organisms as the agents of natural selection exhibits marked contrast to neo-Darwinian natural selection, in the latter of which only the individual organisms are supposed to be exposed to the operation of natural selection. Genes as the agents of natural selection in fact refer to genic variability proceeding in the individual organisms. Although this reminds us of somatic variability of genes, what results is the inheritance of acquired variability, but not acquired traits. Genes as the agents of evolutionary variability survive as long as it is correctly observed that natural selection operates in an opportunistic manner by distinguishing the definiteness in the record from the indefiniteness of anticipation. Agents of internal measurement in general, or natural selection in particular, are of course not restricted to interacting molecules, genes and individual organisms. A biological species can serve as an organized and coordinated entity as much as each individual organism is a functional unity of its constituent organelles and organs (Salthe, 1985). This observation suggests a view such that a biological species can serve as an agent of natural selection as long as it maintains its organizational unity. Natural selection carried by biological species as organized units is of course opportunistic in inducing de novo variability in the carrying species. Natural selection by the agents of internal measurement, though opportunistic in its operation, can go beyond the neo-Darwinian stipulation of the selection of products. Furthermore, recognition of internal measurement in the biological process of natural selection suggests a bridge crossing between physical processes in general and evolutionary process in particular.

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The uncertainty principle in quantum mechanics points to the role of measurement within the realm of material processes in general, which undoubtedly include biological processes. It is the uncertainty principle which keeps generating local fluctuations in quantities to be conserved on a global scale with material and energy resources serving as the typical quantities to be conserved. Internal measurement, when combined with the physical principle of conservation, allows the uncertainty principle to be the generator of de novo variations. The evolutionary engine imputed to the uncertainty principle is operative all through the temporal hierarchy of material evolution. Natural selection riding on the uncertainty principle, while necessarily opportunistic, keeps modifying the underlying evolutionary engine so as always to make resources for itself available.

Acknowledgments The author would like to express his gratitude toward Stanley N. Salthe and the reviewer of this article for their helpful comments.

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