The complementarity principle and the origin of macromolecular information

BioSystems, 11 (1979) 217--226 © Elsevier/North-Holland Scientific Publishers Ltd.

THE COMPLEMENTARITY INFORMATION

PRINCIPLE

217

AND THE ORIGIN OF MACROMOLECULAR

H.H. PATTEE Department of Systems Science, State University of New York at Binghamton, New York, U.S.A.

I am going to try to revitalize an old and controversial relationship which appears to have lost much of its significance and excitem e n t largely through a kind of superficial familiarity. This is the relation between biological informat,!on and biological structure. It is now c o m m o n jargon even among the most reductionistic molecular biologists to speak of information in macromolecules, such as genetic DNA, hormones or immunoglobulins, as if information were a physical property like their structure and chemistry. But, as Kendrew (1967) and Stent (1968) have so clearly recalled, t h e origin o f molecular biology involved 2 disjoint and even hostile groups: the structurists with an ancestry of experimental X-ray crystallographers going back to Bernal, Astbury and the Braggs; and the informationists with an ancestry in phage genetics associal;ed with Delbriick, but with strong hereditary influences from Schr5dinger and Bohr. As Kendrew and Stent saw it over a decade ago, there existed 2 schools of molecular biologists, "structurists and informationists, three-dimensionists, and one-dimensionists," whose conceptual foundations had little in common. The structurists were largely motivated by the power of their experimental technique, X-ray diffraction, to eventually determine the three-dimensional atomic stucture of proteins and nucleic acids, reflecting what Stent (1968) calls a "down-to-earth view of the relation of physics to biology, namely t h a t at. biological phenomena, no matter what the:Lr complexity, can ultimately

be accounted for in terms of conventional physical laws." By contrast, the informationists were largely motivated by theoretical doubts of the adequacy of physics to explain life, in any reductionistic or purely objective sense. These doubts were suggestively expressed by Bohr (1934) and SchrSdinger {1945) who did not speak in informational jargon, since it did not exist at the time, but who were nevertheless both focusing on informational questions: Bohr on the problem of measurement and its possible interference with vital dynamics, and SchrSdinger on the problem of explaining the incredible reliability of genetic instructions. There was, in these early stages of the informationists' thoughts, a strong feeling that explanations of life would involve, if not direct paradoxes, at least a deeper understanding of the unresolved conceptual and epistemological problems of physics itself. To by-pass more than a generation of scientific development, we now find that the tension between the structure and information schools in molecular biology has been relaxed to a kind of loose acceptance of both structural and informational language, usually at only a metaphorical level, that has very little to do with precise physical language in either case. This relaxation was largely the result of theWatson-Crick double helix which combined genetic informational concepts with a chemical structure model of DNA. As Brenner (1974) interprets it, " L o o k i n g back, one can now see that the double helix brought the realization that information in biological

218 systems could be studied in much the same way as energy and m a t t e r . " Adding to the legitimacy of such mixed usage of classical informational and structural concepts were independent developments in the study of the conceptual relation of Shannon's (1949) definition of information, derived from communication engineering, to the thermodynamic and statistical mechanical definitions of entropy. The attempts to relate information to thermodynamics, statistical mechanics and microscopic order in physics has a much longer history than information theory and molecular biology, a profound history that began with Clausius amd developed through Boltzmann, Maxwell, Gibbs and Poincar~. In this century, the relation of information to microscopic description remains a fundamental question in the interpretation of q u a n t u m measurement (e.g., Jammer, 1974; d'Espagnat, 1976), as well as in the relation of statistical mechanics to microscopic dynamics. At the cost of great oversimplification, we may simply observe that for many purposes the definition of information, as defined by Shannon, is now c o m m o n l y accepted as of the same nature as the concept of entropy, so that it is apparently easy to study information with the same conventions that one uses in statistical mechanics (e.g., see Brillouin, 1962, for review). We therefore find many physicists, as well as molecular biologists like Brenner, supporting the view that information is a property of physical systems and that it can be treated as just another physical quantity that is of the same nature as other thermodynamic variables {e.g., Tribus and McIrvine, 1971; Layzer, 1975). Finally, I should quote Delbrfick {1970) from his Nobel lecture: "Molecular genetics, our latest wonder, has taught us to spell out the connectivity of the tree of life in such palpable detail t h a t we may say in plain words, 'This riddle of life has been solved.' The ideas of information storage, of the replication of the stored information, and of its

programmed readout have become commonplace and have filtered down into the popular magazines and grade school text books."

What is the question? I believe that this apparent resolution of the initially divergent attitudes of the structurists and informationists of molecular biology is an evasion of the original and fundamental issues. I am sure that what we mean when we speak of biological information, whether it is in the gene or in the brain, involves much more elaborate connotations than simply a negative entropy or a measure of objective order. We do n o t actually use the word information as if it were just another physical variable like energy or matter. We may indeed have information about energy or matter, but that is not a statement of physics. That is a statement about epistemology, and that is where the original fundamental issue lies. The question is whether information is to be treated in biology as just another physical variable, or as the characteristic and exclusive aspect of living systems and their artifacts that distinguish living systems from all other physical systems. To put the question in a particularly controversial form: Can the biological information that distinguishes living systems from non-living systems be reduced to physical laws.~ Clearly I am not going to finally resolve this old issue here, but as I stated at the beginning, my principal aim is to revitalize the issue. I wish to avoid 2 unproductive attitudes, the 1 of assuming that the question is completely irrelevant, and the other of assuming that the answer is completely clear. I shall develop the following ideas in this paper: (1) The concept of information in biology is complementary to the concept of physical structures and laws. I use complementary here very much in the same sense proposed by Bohr (e.g., 1934, 1963}, which includes: (a) the epistemological distinction between

219 a measuring device, represented as a sourced of information, and the object of measurement represented by causal laws, structures or events; (b) the reqt~irement for explanation that includes completeness in the description of all relevant features of the measurement-object (information-structure) interaction,;, and; (c) the general incompatibility of subjectobject (information-structure) concepts which appear as contradictory if combinded into a single, formal representation (see Jammer, 1974; d'Espagnat, 1976). (2) A primary complementarity of biological structure and biological information is between the rate-independence of molecular or macroscopic informational constraints and the rate-dependence of quantum, classical and statistical laws. Biological information is therefore more complex a concept than t h e r m o d y n a m i c information which also involves complementarity, not in terms of rates, but in terms of time. This is the complementarity of reversible microscopic laws and irreversible macroscopic observations (Misra, 1977). (3) All biological information originates from measurements. A rate-independent informational constraint that is coupled to a rate-dependent dynamics is a necessary condition for a measuring device. The enzyme molecule is the simplest case of a measuring constraint. An explanation of its rate-independent specificity and rate-dependent catalytic dynamics presently require complementary descriptions. (4) Biological information ultimately originates by natural selection which requires both rate-independent molecular constraints at the genetic level coupled to rate-dependent differential birth rates at the phenotypic level. Natural selection is therefore considered as a complex type ot! measuring process. (5) The question o f whether biological information cml be reduced to physics is epistemologicall:~' equivalent to the question

of whether there exists an explanation of measurement processes that can be reduced to laws of nature.

Linguistic, classical and quantum complementarity Let me begin talking about the complementarity of physical structure and information at the level of ordinary language. When we say we have a law or an explanation for some set of our experiences, what do we mean? I believe we mean that this set of experiences appears to be an inexorable pattern or regularity, and that imaginable alternative patterns are excluded by the law from actually occurring. This idea of explanation long predates the concept of physical law with its principles of parsimony and universality. Even mythical explanations requiring the ad hoc intervention of gracious or petulant gods were only stories to exclude, by a power greater than man's, those events which, though imaginable and perhaps desirable, did not in fact occur. Wigner (1964) has expressed it this way: If we have an explanation of events, then these events " . . . should not produce any surprises for us. We should always have the impression that it could not be otherwise." Therefore, to explain a given structure means that in this case there can be no alternative structures. Now if we mean anything at all by a structure containing information, it is the opposite, i.e., that alternative structures are just as possible as the one we actually observe. This is an example of the conceptual objectsubject complementarity of ordinary language. It is significant that the literal root meanings of explain and inform are near opposites, explain meaning to make flat or remove form, and inform meaning to give shape or generate form. This may appear as a somewhat naive example o f complementarity, but as Bohr often pointed out, ordinary classical language concepts are all we have to ultimatedly interpret and communicate the results of our observations and our theories.

220 The classical physics paradigm introduced a new form for this linguistic complementarity by expressing the laws of nature as ratedependent equations of motion which are universal. Information a b o u t particular systems can only be obtained by measurement of the initial conditions. A complete explanation of the behavior of an object in classical physics is believed to consist of the integration of the equations of motion under a complete set of initial conditions (i.e., Laplacian determinism). We may also think of the initial conditions as that part of our experience which could not be specified by the laws. This is in fact a definition of initial conditions (Wigner, 1964). In other words, classical explanation sharply divides our experiences into 2 classes, those experiences for which we have found very simple, precise and universal descriptions in the form of rate equations, which we call laws, and those experiences for which we have found no general or simple description whatsoever, which we call initial conditions. Classical information therefore only has meaning with respect to initial conditions. The only process by which the values of initial conditions can be obtained is called measurement. However, the theory does not tell us what measurement is or when it occurs, and this is where the basic epistemological differences begin ! In classical physics it is assumed that only the final results of measurement, that is, the numerical values, are the relevant information one needs to explain and predict the behavior of the system. In fact, this assumption accounts for the classical definition of information. If all initial conditions are known precisely, then the behavior of the system is completely predictable from the equations of motion, and no alternative behaviors are possible within this description. The measuring device itself is assumed to have vanishingly small physical interaction with the system and, in contrast to quantum theory, the act of measurement is not recognized in the formal model.

To the extent that we decrease the quantity of information about initial conditions, there is a corresponding increase in alternative trajectories available to the model. This gives rise to the equivalence of information and negative entropy. Of course this association of laws, measurements, information and entropy also raises the issue of the relation of classical description to t h e r m o d y n a m i c or statistical description which I believe is only one more aspect of the more f u n d a m e n t a l epistemological complementarity inherent in the concepts of subject and object. An enormous effort has been devoted to the formal reconciliation of irreversible thermodynamic or macroscopic description with the reversible microscopic laws of motion. I know of no adequate review of this area, however, for some recent approaches, see Prigogine, Mayn~, George and deHaan (1977) and Misra {1978). Prigogine et al. claim that their procedure provides a microscopic theory for irreversible processes, whereas Misra concludes that the relation between the thermodynamical and the microscopic dynamical description of physical system is, " . . . an instance of complementarity, quite similar to the complementarity encountered in quantum mechanics." Quantum theory does not allow this precise conceptual distinction between laws and measurements or between the objective structure being measured and the subjective agency of measurement. In quantum theory we must say that not only the data but the nature of the measurement itself is an essential source of information. That is, the set of alternatives which are to be reduced in number by observation are determined by the entire measurement situation. The system that is being discussed in fact includes the measuring agent and its arrangement with the object. The numerical result still represents classical information, but not about a classical object. This information is about the object plus measuring device as a system. The description of causal laws of this system is incompatible with the description of classical information

221 as derived from a measurement. This is basically Bohr's quantum mechanical statement o f the complementarity principle. However, it is significant that Bohr did not think o f this principle as an ontological principle conceJ:ning only fundamental particles, but as a much broader epistemological principle that " . . . bears a deep-going analogy to the general difficulty in the formation of human ideas, inherent in the distinction between subject and o b j e c t " (Bohr, 1928). The problem of measurement in quantum theory is also much too involved and controversial to discuss here (see Jammer, 1976; d'Espagnat, 1976 for review). However, I would emphasize 2 points. First, while it is understandable that biologists would want no part of these intricate controversies, it does not follow that our conception of living processes will be independent of the outcome of these controversies. In other words, the physicists' present inability to resolve the problem o f measurement does not imply anything about the importance of measurement interactions within living systems. Second, while it is also understandable that physicists thinking about measurement theory would not want to learn the details of molecular biology, it does not follow that knowledge of measurement processes at the simplest molecular levels would be irrelevant for modelling most complex measurement processes which involve the highest cognitive levels. In other words, the central epistemological problem of quantum measurement must arise when measurement first occurs. I have argued (Pattee, 1971, 1972) that this must occur where information first appears, and this is at the origin of life, not at the origin of quantum theory. I believe that the 2 schools of molecular biologists were originally divided by their epistemological positions toward measurement, the strucl:urists deriving their attitude from the "down-to-earth" classical view toward measurement as merely a source of information a b o u t c,bjective structures and not itself a part of explanation of the system; and

the informationists deriving their attitude from the more subjective quantum mechanical complementarity principle that explanation must take account of the total informational aspects o f measuring device and object structure which as a whole make up the system being explained. It is quite obvious that the structurists' classical epistemology dominates biology at the present time. Stent (1968) makes it clear that even those molecular biologists who had originally been motivated by quantum mechanical complementarity, including himself, had given up hope long ago that paradoxes would turn up. Under the circumstances, that is, since physicists cannot agree on the interpretation of measurement or complementarity, the classical paradigm for living matter is understandably the most popular. On the other hand, it requires wishful thinking to believe that life has been explained in terms of physics, when a quantum mechanical description of enzyme catalysis has not been carried o u t and the epistimological foundations of physics have not yet been agreed upon by physicists. Indeed, the problem of the subject-object complementarity has not been entirely dismissed by biologists. To quote Monod {1971), "No, the real difficulty is not in the physics of the phenomenon; it lies elsewhere, and deeper, involving our own understanding, our intuition of it. There is really no paradox or miracle; but a flagrant e p i s t e m o l o g i c a l c o n t r a d i c t i o n . " And Monod concludes, "In fact the central problem of biology lies with this very contradiction, which, if only apparent, must be resolved; or else prove to be utterly insolvable, if that should turn out indeed to be the case."

Rate-independent information; rate-dependent laws These foundational questions of physics often seem far removed from the issues of biological information and structure, and since their clear resolution does not appear im-

222 minent, I prefer to emphasize a more phenomenological c o m p l e m e n t a r i t y between descriptions o f biological structure and descriptions of biological information that still illustrates the essential problem. Whenever we are describing biological structures or events in terms of physics or chemistry, we express the model in terms of a rate equation with initial conditions in the paradigm of classical physics. These rate-dependent models are used at all levels of organization, from SchrSdinger's equation up through classical dynamics, equilibrium thermodynamics, chemical kinetics, non-equilibrium dissipative structures and growth phenomena, including the t h e o r y of natural selection. By contrast, whenever we are describing biological information, we speak of the order or sequence of events but never express the process by rated e p e n d e n t functions. This is a very general p r o p e r t y o f information, whether it is embodied in the bases of DNA, morphogenetic patterns, the program of a c o m p u t e r or in logical, mathematical or ordinary languages. The meaning, significance or o u t c o m e o f biological i n f o r m a t i o n does not depend on the rate at which the information is read or transduced. In other words, biological informational events are c o m p l e m e n t a r y to events governed by laws with respect to their rate dependence. This is not a statement derived from physical th eor y, but a simple, ordinary language observation. When the cell is synthesizing a protein, or when a c o m p u t e r is executing a program, or when I am explaining c o m p l e m e n t a r i t y , t h e informational aspects of these processes do not depend in any functional sense on the rate of syntheses, the rate o f c o m p u t a t i o n or the rate of writing or reading. If i n f o r m a t i o n has any meaning, then what it means does not depend on how fast it is expressed. We cannot imagine that the type of protein synthesized can depend on the rate o f transcription, any m or e than we can imagine that the plot of a novel can depend on the rate at which it is read (Pattee, 1977). The fact t h a t information is always transmitted or read at s o m e rate is incidental, and irrelevant for this argument.

Consequently, according to the classical paradigm of explanation, informational constraints cannot be reduced to rate equations, that is, t h e y cannot be integrated in time along with the rate equations describing the laws. All informational systems must t herefore be supported by non-integrable constraints. Such constraints we often recognize as the rules or syntax of the informational system (Pattee, 1973). By c o n s t r a i n t , we mean an alternative "subjective" description of a structure that, of course, in the " o b j e c t i v e " physical mode can also be described by the equations of motion. Our description of a constraint's informational rule behavior is c o m p l e m e n t a r y to our description of the laws in the same sense t h a t our description of measuring devices is c o m p l e m e n t a r y to our description of laws. There is no way that the description of a measuring device as only a constraint can lead us to a description of the laws, nor can a description of the laws alone be used to infer the constraints of a measuri:]g device, although there is no question that ~he measuring device is also correctly descriged by these laws. In the same sense, there is no question that the structure of nucleic acids and the synthetase enzymes making up the genetic "code system o b e y q u a n t u m mechanical laws. However, a complete detailed q u a n t u m mechanical description o f these structures would give no more clue to the meaning of a DNA sequence as biological information than the chemistry o f this ink and paper would give a clue to the meaning of these words. Conversely, a complete description of the code constraints and functions c enzymes would give no clue to the laws of nature under which these molecular structures can be described microscopically. This sharp conceptual distinction I have made between rate-dependent and ratei ndependent processes can of course be challenged o n t he same grounds that the distinction between reversible and irreversible phenomena are challenged. For example, behavior that is reversible in a system with a small n u m b e r of particles will appear as

223 irreversible if one, has a large number of particles (e.g., P. & T. Ehrenfests's urn model). From this type o f model it can be argued that reversibility and irreversibility are not sharp distinctions but only a matter of degree, the microscopic reversible description being the more objective (i.e., obeying the laws of motion), and the irreversible description being more subjective {i.e., depending on the observer's inforraation about the system). In a similar way it can be argued that the ratedependent microscopic laws are the objective reality and the rate-independent measurement constraints are only a practical, subjective simplification of systems with many degrees of freedom. I regard these arguments as not incorrect, but irrelevant to the epistemological issues of what constitute,; measurement, information and e x p l a n a t i o n The complementarity principle can be considered as an epistemological position that finds both subjective and objective modes of description necessary for explanation. In fact, if we should actually achieve a mic:roscopic rate-equation description o f the measurement constraints for the system we are "explaining", we would find that not only the measurement but the system we originally had in mind would disappear, only to be replaced by a new system with an immense number of new initial conditions requiring new measurements. One can recogni:,e this process as related to what we call reductionistic explanation where one has explained away the original system. There is no doubt that reductionistic explanation is often needed, especially when the principles of the microscopic system form a more practical or elegant explanation, say in terms of values such as universality, simplicity, coherence, ease of computation, etc. The essence of the measurement problem at the quantum mechan:ical level is that reductionism apparently "expl~tins a w a y " the measurement itself. The most popular response to this loss is the introduct:ion of the observer as an irreducible subject o f the measurement explanation. I believe it is the apparent need

for this epistemologically irreducible observer that creates the skepticism in some physicists about the reducibility of living systems. However, let us return to the phenomenological description of biological information.

All biological information measureme nts

originates

from

In the last section I characterized biological information by its rate-independent relation to the dynamics which it constrains. The essential characteristic of a measuring device is that it must couple a rate-dependent dynamical system with a rate-independent information system. I do not wish to distinguish measurement from control in this paper (see Pattee, 1973) except to point out that a measuring device is a non-integrable constraint that acquires information from a rate-dependent dynamical system while a control system is a non-integrable constraint that influences the rates of a dynamical system. The common essential requirement of measurement and control constraints is that they must couple 2 systems, one described as rate dependent and the other as rate independent. For this reason, the complete explanation of a measurement involves complementary descriptions of rate-dependent and rate-independent processes. A more general condition is imposed since any increase of information requires an equivalent dissipation of energy or increase in entropy according to the t h e r m o d y n a m i c concept of information. In this case a complete explanation o f a measurement will also require complementary descriptions of reversible and irreversible processes (cf. yon Neumann, 1955}. As examples of what I have defined as biological measurement I shall consider here only enzyme catalysis and natural selection, although biological organization involves many hierarchical levels of measurement. I have chosen these 2 only because they represent the 2 extremes of organizational complexity. They are both in effect characterized

224 by an articulation of rate-independent informational and rate-dependent dynamic processes. The enzyme is defined as a specific catalyst where the concept of specificity requires an informational selection from alternatives while catalysis is by definition a ratedependent process. Natural selection is far more complex, but it is normally defined in terms of the coupling between genotype and phenotype where the concept of genotype requires informational selection driven by the rate-determined dynamic selection at the phenotypic population level. What is the essential nature of this articulation between the rate-dependent dynamics and the rate-independent constraints that characterize informational processes? The essence of such a non-integrable constraint is that (a) the characteristic action of the constraint does n o t appear unless a specific dynamical triggering action takes place, and (b) this specific action of the constraint has no necessary physical relation to the laws of the dynamics that triggered it. The extreme physical case of an informational constraint is a switch which is passive until an external force of a specific type acts as a trigger, leading to consequences that have no necessary physical relation to the nature of the triggering event. The logical extreme ignores physical description altogether so that the concepts of laws and rates disappear and we have only a formal or purely symbolic switching function to which we may still apply informational measures. In this case there is meaningless information and no measurement. On the other hand, if we could describe a real switch in terms of its microscopic dynamics, we would find that all the laws of nature are strictly followed and we would have a complete description w i t h o u t the concept of biological information. In this case there are many more physical details, but again no measurement. Therefore, although we can clearly reduce the structures and behavior of these peculiar constraints to physical laws, it is not clear how we can reduce to physical laws the biological information that distin-

guishes a measuring device from all other possible structures which also obey physical laws. Apparently only coordinated biological systems can supply this information (cf. (Polanyi, 1968). The situation with enzymes is very similar. Enzymes may be considered as functionally analogous to switches where their substrates correspond to switching inputs, and the reactions they catalyse correspond to outputs. With regard to this reaction, they are entirely passive until they bind a specific substrate. Furthermore, the catalytic reaction has no necessary physical relation to the chemistry of the substrate. There is no doubt that enzymes may be usefully described abstractly as switches in an information network, and also concretely in terms of their detailed structure, binding and catalytic behavior. In principle the enzyme could be reduced to the quantum mechanical level of description, but it would not explain the informational constraints that distinguish this molecule as a part of a living system. This information is of course supplied by the structural gene which ultimately originates this information by natural selection. These molecular constraints are measuring devices only in the context of this larger coordinated system. Furthermore, we recognize only this larger coordinated system as alive. Such an irreducible threshold of coordination forms what I believe is equivalent to the subjective side of the epistemological complementarity of subject and object. Quite independently of these epistemological conditions, it is generally agreed that the ultimate origin of biological information is natural selection {e.g., Kimura, 1961). Therefore one might in principle take this entire evolutionary system and try to reduce it to objective physical laws. Indeed this is precisely what Eigen (1971) has proposed: " I f we want to close the gap between physics and biology, we have to find out what 'selection' means in precise molecular terms which can ultimately be described by quantum mechanical t h e o r y . " While this is certainly one mode of description in which some aspects of

225 natural selection can be represented, it is by no means clear that such an objective physical description will adequately explain what selection means to the subjective organization any more than the laws of quantum theory explain what measurement means to the observer.

Conclusion There is general agreement that biological systems need both structural and informational concepts for their description. However, whether these concepts are related in a reductionist sense or a complementary sense is not yet resol~ed. W e m a y as practical biologists agree, with Delbrfick, that "This riddle of life ha., been solved," but we cannot as critical phy,;icists say, "This riddle of physics has been solved." If biological information original~es only by measurement processes, then w e need a m u c h clearer episternological idea of measurement before we can interpret our mathematical theories as explanations of life. A valid mathematical model that usefully describes certain structural features of a biological information system m a y indeed, by analogy with the classical paradigm c.f physical models, m a k e us feel that information is just another physical variable; but until we can agree on what we m e a n by an explanation of the measurement process, we have little reason to claim that life has been reduced to the laws of physics.

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226 COMMENTARY C.H. Bennett T h e historical o p p o s i t i o n b e t w e e n i n f o r m a t i o n a n d s t r u c t u r e in m o l e c u l a r b i o l o g y seems t o me t o be p a r t o f a d e e p e r o p p o s i t i o n or c o m p l e m e n t a r i t y b e t w e e n i n f o r m a t i o n a n d f u n c t i o n , r e c e n t l y e m p h a s i z e d b y Eigen. S o m e s t r u c t u r e s are b e s t viewed i n f o r m a t i o n a l l y , o t h e r s f u n c t i o n a l l y . N o w a d a y s t h e r e is n o t t o o m u c h m y s t e r y , in principle, in t h e causal c h a i n c o n n e c t i n g a gene's s e q u e n c e w i t h its p r o d u c t ' s static t h r e e - d i m e n s i o n a l s t r u c t u r e . A c c o r d i n g l y I w o u l d l u m p the s t r u c t u r e s o f m o s t single gene p r o d u c t s w i t h t h a t of t h e genes t h e m s e l v e s as s o m e t h i n g t h a t can b e u n d e r s t o o d r a t h e r s t r a i g h t f o r w a r d l y in i n f o r m a t i o n a l terms. T h e b i o s y n t h e t i c a p p a r a t u s s i m p l y carries o u t gene's orders w i t h o u t a n y creativity or h a c k t a l k . On t h e o t h e r h a n d are s t r u c t u r e s (e.g., gross a n a t o m y ) w h o s e genetic d e t e r m i n a t i o n involves a great deal of gene i n t e r a c t i o n a n d m o r p h o g e n e t i c timing. T h e s e s t r u c t u r e s deserve t o be p l a c e d in t h e s a m e c a t e g o r y as t h e c a t a l y t i c activities of e v e n small m a c r o m o l e c u l e s , as p h e n o m e n a best u n d e r s t o o d in c o m p l e x , f u n c t i o n a l t e r m s , as e x p r e s s i o n s of " m o l e c u l a r politics," r a t h e r t h a n " m o l e c u l a r m a n u f a c t u r i n g . " A n o t h e r d i s t i n c t i o n , largely parallel t o t h a t b e t w e e n i n f o r m a t i o n a n d f u n c t i o n , is b e t w e e n more-or-less s t a b l e s t r u c t u r e s (e.g., the D N A in a d r y seed or crystallized virus) a n d s t r u c t u r e s r e q u i r i n g m e t a b o l i c activity for their m a i n t e n a n c e . N e i t h e r of these d i s t i n c t i o n s c a n be m a d e e n t i r e l y s h a r p : since D N A is t h e r m o d y n a m i c a l l y u n s t a b l e , n e i t h e r its s t r u c t u r e n o r its i n f o r m a t i o n can he m a i n t a i n e d in t h e long r u n w i t h o u t c a t a l y t i c f u n c t i o n a n d m e t a b o l i c activity. A n d o f c o u r s e t h e c o n t e n t o f t h e genetic message is c o n t i n u a l l y inf l u e n c e d b y its f u n c t i o n , t h r o u g h n a t u r a l selection. A n o t h e r c o n c e p t u a l l y t r o u b l e s o m e c o m p l e m e n t a r i t y or o p p o s i t i o n is t h a t b e t w e e n i n f o r m a t i o n a n d m e a n i n g . A n a t u r a l D N A m o l e c u l e is i n t e r m e d i a t e in i n f o r m a t i o n c o n t e n t b e t w e e n a r a n d o m p o l y m e r a n d a p o l y a d e n y l i c acid m o l e c u l e ( A A A A A . . . ) , y e t it is s u b j e c t i v e l y m o r e m e a n i n g f u l t h a n either. A partial r e s o l u t i o n of this u n c o m f o r t a b l e s i t u a t i o n m a y lie in the n o t i o n of m u t u a l i n f o r m a t i o n , i n t r o d u c e d in S h a n n o n ' s original paper. M u t u a l i n f o r m a t i o n is t h e i n f o r m a t i o n in o n e o b j e c t a b o u t a n o t h e r , while a b s o l u t e i n f o r m a t i o n m e a s u r e s t h e a r b i t r a r i n e s s or u n p r e d i c t a b i l i t y of a single object. A b s o l u t e i n f o r m a t i o n , in t h e f o r m of noise, is easy t o g e n e r a t e in even t h e c r u d e s t m e a s u r i n g a p p a r a t u s , t h e c r u d e r t h e b e t t e r . A n ideally noiseless m e a s u r i n g a p p a r a t u s , o n t h e o t h e r h a n d , or a n e n z y m e t h a t copies DNA w i t h o u t m a k i n g a n y errors, g e n e r a t e s m u t u a l i n f o r m a t i o n ( b e t w e e n t h e original a n d the c o p y ) b u t n o a b s o l u t e i n f o r m a t i o n .