Irreducible Complexity and The Problem of Biochemical Emergence

Biology and Philosophy 14: 593–605, 1999. © 1999 Kluwer Academic Publishers. Printed in the Netherlands.

Irreducible Complexity and The Problem of Biochemical Emergence BRUCE H. WEBER Department of Chemistry and Biochemistry California State University Fullerton Fullerton, CA 92834-6866 USA

A Review of Michael J Behe, Darwin’s Black Box: The Biochemical Challenge to Evolution, The Free Press, 1996, 307 pp., hdbk $24.50, pbk $13.00. Michael Behe raises some interesting and important questions in this book: what are the origins, evolutionary mechanisms and implications of the molecular complexity of biological phenomena? In the light of such complexity can we understand emergence of novel, complex structure/functions? Indeed, these days many regard emergence to be as significant an evolutionary question as adaptation (Depew and Weber 1995; Maynard Smith and Szathmary 1995). Unfortunately, Behe fails to take advantage of this opportunity. Instead he has written a volume that reflects at best a selective scholarship and that employs the rhetoric of polemic rather than dispassionate discourse. What might have been an interesting argument from the Catholic tradition for design, especially in light of the subsequent statement of the Pope accepting the validity of evolution as a theory while allowing that different philosophical interpretations are possible (John Paul II 1997), is ultimately marred by Behe’s proclamation of intelligent design to be a revolutionary paradigm change of Copernican proportions. A revolution that is being resisted by neoDarwinians defending an unproven ideology. A more interesting book could have been written, one that more humbly explored the possible ways that evolutionary biology, and science more generally, could engage in dialogue with theology. I will focus primarily on the question of whether complexity, as Behe represents it, is indeed irreducible, if such complexity is beyond scientific scrutiny as Behe implies, and what is implied or not by the existence of such complexity.

594 In effect, Behe restates in purely modern biochemical terms William Paley’s argument that there is an irreducible complexity to living beings that suggests the action of a designer-creator. He repeats Paley’s challenge for science to provide a naturalistic explanation that can account robustly for such complexity and adaptation. Behe’s assertion of irreducible complexity also echoes Kant’s famous dictum that there can never be a Newton of a blade of grass. Darwin responded to Paley’s challenge by suggesting that the mechanism of natural selection acting upon random, heritable variation could account for biological adaptation and descent with modification. For this accomplishment many regard Darwin to indeed be the Newton of a blade of grass. But, Behe argues Darwin could not have known what we now know about organisms and lineages of organisms at the biochemical and molecular level. This knowledge, he claims, stretches the explanatory power of Darwinian conceptions to and beyond their limit, leaving us only with the alternative of intelligent design to explain the emergence of novel and complex structures and phenomena in living systems. Behe does not deny that natural selection can act on populations to cause changes in gene frequencies. Nor does he deny the occurrence of mutations. Indeed, he accepts that mutations in amino acid sequences of proteins provide evidence for descent with modification. To this extent Behe acknowledges biochemistry as supporting the fact of evolutionary change. However, he sees the systems of proteins and enzymes involved in particular biological tasks, such as the bacterial flagellum, signal transduction at membranes, transport across membranes and within cells, blood clotting, the immune system, and the origin and regulation of metabolism as having too many components that have to interact in precise ways for such systems to have evolved by a piecemeal, gradual process of natural selection. It is not that a primitive eye or flagellum might not have a selective advantage but rather that to get even to such primitive structures would require a large number of molecular changes that would not have any functional value until all the minimal molecular components were in place. To convince us that this is so Behe attempts to impress upon us the biochemical complexity of specific examples. He then argues by an analogy with a mousetrap that, just as there is no way we could imagine catching mice unless all five essential components of the mousetrap were in place simultaneously, we cannot imagine how any complex biochemical system could have evolved one component at a time. This latter feature he imagines Darwinian natural selection requires, since lacking even one element of the system would prevent useful or adaptive action and all change must be gradual. Therefore, the complexity of the biochemical examples Behe cites, he asserts, could not have arisen except by design as in the case of the mousetrap, all other alternatives presumably being ruled out. He

595 insinuates that this irreducible complexity is either ignored by contemporary scientists or is explained away by “just so” stories in order to protect the Darwinian paradigm. Behe makes much of the supposed lack of attempts by evolutionary biologists to provide credible causal explanations of the emergence of precisely such complex adaptive systems. Unfortunately Behe does not give credit to what work has actually been done by the Darwinian research community. Further, he virtually ignores a whole area of current research on self-organizing, emergent phenomena. Aside from the comfort his argument gives to some types of creationists, there has been considerable interest in and an active response to Behe’s book. A number of published reviews of Darwin’s Black Box (see for example Cavalier-Smith 1997 and Blackstone 1997) have appeared. Also there are several web sites devoted to critiques of Behe as well as to summaries of the current research Behe either missed or misrepresented (see for example “Behe’s Empty Box” http://www.spacelab.net/∼catalj/box/behe.htm, “A Response to Michael Behe” http://mcgraytx.calvin.edu/evolution/irred _compl.html, “A Reducibly Complex Mousetrap” http://udel/∼mcdonald/ mousetrap.html, and “Published Works on Biochemical Evolution” http://www.spacelab.net/∼catalj/box/published.htm;). For example, Behe’s account of the bacterial flagellum asserts that more than 240 protein components are required to produce a functional structure that can propel a bacterium up a nutrient gradient. Just as there are five components needed to have a functional mousetrap, Behe cannot imagine how anything short of the full 240 components of the flagellum could propel a bacterium. But only 33 proteins are needed to produce a functional flagellum for Helicobacter pylori (Ussery, Bios, in press and http://www.cbs.dtu.dk/ dave/Behe.html), suggesting that less complex but functionally adaptive versions of the flagellum can exist. Further, mutants of Helicobacter pylori that render some of these proteins non-functional do not completely prevent the propulsion provided by the flagellum, suggesting that the minimal complexity is even less. This does not obviate the problem of the emergence of the flagellum. It does suggest that the problem is not as daunting as Behe portrays it. Research on biochemical topology of bacteria and fungi suggests that a variety of the ionic gradients, produced by the metabolic action of these cells, may play a role in organizing cellular structures in development and evolution (Harold 1991). The self-organizing tendencies of biochemical systems may help guide the formation of complex, patterned structures that can subsequently acquire functional value for which improvements can be selected. This does not pretend to provide a complete explanation, but it does suggest directions for future research, a point to which I will return below.

596 A classic problem for the emergence of novelty is one upon which Darwin ruminated, the evolution of the eye. Behe cites as evidence for design the large number of proteins and enzyme activities required for even a simple photosensitive spot. Bacteria have photosensitive enzyme systems that involve complex reaction patterns and are used for energy transduction (Harold 1986; Nicholls and Ferguson 1992); related genes are also found in lineages of multicellular organisms where they are often put to alternative uses Kleinzeller (1995). It turns out that one of the protein components of the lenses of eyes is closely related to and likely evolved by a process of gene duplication and divergent evolution from heat shock proteins (Wistow 1993). Another protein component varies in a number of taxa, but in each case is a duplicated and diverged enzyme used elsewhere in metabolism (over nine different enzyme ancestors have been observed, Wistow 1993). Thus there is no real mystery about the potential source of gene products for novel functions. Still, there is the legitimate question of how such components could organize to produce a selectable proto-function in the first place. Another example used by Behe is the complex enzymology of vertebrate blood clotting, which involves roughly 10,000 genes. He makes fun of a popular presentation about the possible origin of such systems presented by Russell Doolittle, which, although up to date, did not address the actual molecular mechanism on a technical level, using instead an entertaining “yinyang” metaphor (Doolittle 1993). Behe does not refer to nor use the scientific article upon which the popularization was based (Doolittle and Feng 1987). Doolittle and Feng analyze comparative sequences of the enzymes involved to establish evolutionary relationships and to track possible exon shuffling to create a family of enzyme activities capable of catalyzing the cascade of reactions involved (see also the more recent Doolittle 1995, which discusses the mechanisms and combinatorial advantage of such shuffling). The basic mechanisms of gene duplication and exon (or domain) shuffling, which most likely provided novel enzyme activities and families of enzymes during the course of evolution, are well documented and are discussed in readily available works on molecular evolution, both at the popular level (Wills 1989, 1991) and in the technical literature (see for example Patthy 1991, 1995; Doolittle 1995; Li 1997). These proposed mechanisms are based upon a wealth of molecular data. Although no one can time-travel to observe or experimentally test what happened in the past – perhaps only this would fully satisfy the criteria in the back of Behe’s mind but there is no reason for scientists to demand this criterion – there are ways in which notions about a putative evolutionary pathway for the emergence of a system such as blood clotting can be subjected to empirical testing and possible falsification. For example, on the basis of available sequence data Doolittle has deduced that

597 certain enzymes of the blood clotting cascade would be absent in jawless fish, which is something that can be experimentally determined. This points toward a robust research program, not a “just so” story. We are at the point of accumulating enough data from DNA sequences and three-dimensional structures of proteins to make a number of tests of putative evolutionary explanations in the near future. In another of Behe’s examples, the multigene family of the immunoglobins, we in fact know not only that exon shuffling is important, but that a range of other phenomena occur on the molecular level that give clues to the origin of the system and suggest mechanisms that may be important in evolutionary processes generally (Campbell 1983; Wills 1987, 1991). Behe does not explore such developments in the field or their potential explanatory power to deal with questions of the emergence of complexity. Although he thinks that an account of the origin of the immune system is beyond the capacity of Darwinism, the recent report of the discovery of function of the RAG transposases and transposons in contemporary vertebrate immune systems and of the possible role that the introduction of such an activity could have had on the emergence of the vertebrate immune system (Agrawal, Eastman and Schatz 1998), reveals the danger of assuming that the complexity of any system is not open to an evolutionary explanation. A research program is now possible that can explore by sequence analyses and computer simulations putative routes of emergence of the immune system, and hence of complex vertebrates who could not exist without their immune systems. If intelligent design were the prevailing paradigm, research would be stopped at delineating the function of these transposons/transposases. It begs the question to think evolutionary theory cannot make progress on their origin. When it comes to questions about the origin, or more correctly the emergence, of life, Behe says that little has actually been done and that what efforts have been made have been inadequate. Behe depends primarily upon computer searches of the titles in the Journal of Molecular Evolution to argue that there is little effort by evolutionary biologists to address the problem. There are two difficulties here. Titles are not a sure guide to content. For example, an article on the origin of the tRNA synthetases, which are essential for modern cells and for the emergence of life, was published in 1995 in the Journal of Molecular Evolution, but the title only refers to phylogenetic analysis, and hence was missed by Behe (Nagel and Doolittle 1995). There have been papers on the origin of life published in the Journal of Molecular Evolution that that also eluded Behe’s search net because they do not have the word “origin” in their title, such as one on the role of membrane-like structures and thermodynamic gradients in the origin of proto-cells (Morowitz,

598 Deamer and Smith 1991). In fact, most of the literature on origin of life is not published in the Journal of Molecular Evolution, but rather in journals such as Origins of Life and Evolution of the Biosphere, Nature, or Journal of Theoretical Biology, in which Behe could have found a large number of both theoretical and experimental papers addressing the origin of life. Behe, for example, could have found papers that address how amphiphiles derived from carbonaceous chondrites can give rise to membrane-like structures such as micelles and vessicles (Deamer and Pashley 1989), how such structures show autocatalytic self-assembly and self-replication (Bachmann, Luisi and Lang 1992), and how polycyclic aromatic hydrocarbons, also derived from meteorites, can embed and orient in amphiphile bilayers in such a way that proton translocation, an important cellular energy-transducing mechanism, can occur (Deamer and Harang 1990). There are also key books that Behe apparently did not consult, such as standard accounts by Loomis and Eigen, as well as those that seek to bring to bear on the problem of life’s emergence the conceptual methodology of thermodynamics and self-organization by Fox, Wicken and Morowitz (Loomis 1988; Eigen 1992; Fox 1988; Wicken 1987; Morowitz 1992). Whether or not Behe finds such work compelling, he at least owes it to his readers to report that such efforts in fact exist, since he makes much of their supposed absence. One attempt to address the origin of life does receive some attention from Behe, that of Stuart Kauffman in his Origins of Order (Kauffman 1993). Behe provides an extraordinarily brief and incomplete summary of Kauffman’s program. He argues that Kauffman only can get self-organization to occur in his computer simulations under specific initial and boundary conditions and that only certain types of interactions among the components of his models lead to organized behavior. Since self-organization does not arise by totally random chance events, but requires certain “propensities” of interaction and further some type of selection, Behe concludes that Kauffman’s approach can be safely dismissed as irrelevant to the problem of the emergence of living systems. Behe seems to miss the whole point of Kauffman’s exercise. What is extraordinary about Kauffman’s models is that, although simple, they do capture a range of dynamical behavior of biological systems (Depew and Weber 1995). Of course constraints have to be built in by the programmer. The question is whether these constraints are reasonable, reflecting at least by analogy the categories of local interaction between components and being away from equilibrium. That is, to the extent that Kauffman’s models reflect the effect and consequence of built-in propensities of molecular properties and interactions as well as the energy flow and entropy production of real physical and biological systems, they can be explored in simulations to give insight into possible large-scale events in natural systems. The propensities exist

599 in nature (Ulanowicz 1996); to model their existence the programmer must introduce some sort of similar constraint. To demand that self-organization emerge from a totally ergodic system is to deny that there are propensities, initial and boundary conditions in the real world. I have argued that Kauffman’s models do provide important insight into what might have been important for the emergence of life (Weber 1998a). His notions of protein-sequence phase space and how it might be explored coupled with his concept of catalytic-task space provide an approach to consider how ensembles of initially random sequences could, over time, be selected by chemical selection for catalytic and thermodynamic efficiency, to better fit various catalytic tasks. Another key insight is that of catalytic closure, by which ensembles of autocatalytic polymers of sufficient complexity can undergo a “phase transition” to a closed, emergent “proto-metabolism.” Natural physical and chemical systems under appropriate initial and boundary conditions of energy/matter gradients and flow show spontaneous self-organization, generating macroscopic ordered structure under thermodynamic imperatives of dissipation away from equilibrium (Nicolis and Prigogine 1977, 1989). The approaches employed to describe such phenomena have been extended to biological systems including the problem of the emergence of life (Wicken 1987; Brooks and Wiley 1986, 1988; Swensen and Turvey 1991; Morowitz, Deamer and Smith 1991; Ulanowicz 1997). The ways in which atomic and molecular properties and propensities could interact under such thermodynamic constraints in the earth’s early environment, as well as the role of physical and chemical selection in producing more complex emergent phenomena, have been summarized in the important and admirable The Natural Selection of the Elements (Williams and Frausto da Silva 1995). Harold Morowitz has provided a suggestion from the evidence that he and David Deamer have obtained that early prebiotic events would not necessarily have to occur in dilute solution, but rather within an osmotic and thermodynamic barrier of amphiphile molecules analogous to those comprising the membranes of modern cells (Morowitz 1992; Deamer 1992). This suggests that the chemistry envisioned by both Kauffman and Wicken would occur within a proto-cell and that life and its components emerged and became more articulate as a whole rather than sequentially, just as Kauffman’s simulations suggest (Weber 1998b). In such emerging, protocellular systems, it might have been possible, even with weakly catalytic molecules, for some chemistry to occur, such as the attachment of purine and pyrimidine bases to ribose that is required for the emergence of the ‘RNA world’, which would otherwise be difficult under abiotic conditions (Joyce and Orgel 1993). These theoretical considerations point the way toward

600 both simulations and experiments to further test such possibilities about the emergence of life. Such an account of the emergence of living systems suggests that biological selection (natural selection) of the reproductively fit, as a phenomenon, arose out of the earlier and ongoing action of physical selection for the stable and of chemical selection for the energetic and catalytic efficient as life and genetic information emerged (Weber and Depew 1996; Weber 1998b). This does not represent an “imperial” insertion of natural selection language into discourse about an abiotic and pre-biotic world, as charged by Salthe (Salthe 1997) or a use of natural selection to explain natural selection as charged by Behe (Behe 1996). Rather, it represents a recognition that there are various types of selection, that they themselves are emergent, and that these can interact with self-organizing properties of different types and levels of systems (Weber and Depew 1996). Selection may not have to do everything, nor only in a gradual manner, since selection can be allied with self-organization to generate order and organization, sometimes in a global manner (Kauffman 1993; Weber and Depew 1996). Clearly, neither does self-organization have to do everything by itself. Nor should any rational person expect that chance alone could generate order out of chaos. All three should be considered as acting together, to various degrees in specific instances, in order to generate robust explanations of emergence. The application of ‘complex systems dynamics’ to biological problems is still in its infancy. Nonetheless, the point is that there is a research community, which includes some “card-carrying” Darwinians, that is attempting to address problems of emergence in general and especially in biological systems and thereby to give accounts of what Behe takes to be “irreducible complexity.” Even though this approach is controversial, it is strange that Behe does not attempt to address the issue of self-organization (or better system-organization) beyond his short critique of Kauffman. Of course, the possible implications of such an approach disrupts the dichotomy Behe has set up of selection or design, so one can understand why he wants to avoid it. Behe’s claim of irreducible complexity of biochemical systems is weakened by the actual scientific literature. But it is still an important issue that needs to be addressed. Behe’s claim that no one is attempting to provide evolutionary explanations of such complexity is inaccurate and is based on his unawareness of the on-going published work in this area. Behe’s argument that we cannot explain the biochemical basis of complex biological organization is, in its essence, an argument from ignorance, much like one Paley invoked. That is, Behe argues that he cannot imagine how the phenomena of the emergence of “irreducibly” complex biological structures could be explained by invoking selection alone, therefore our only alternative is to

601 accept the only other possibility, namely intelligent design. We can respond to this in at least two ways. First, biologists with greater imagination and information may come up with explanations invoking only selection; second, the application of complex systems dynamics may show how to understand the emergence of the type of functional complexity that concerns Behe. Either is an incomplete work in progress, which is the characteristic of a living science that works with a human perspective. The demand for an immediate and complete explanation that can only be satisfied by a “God’s-eye view” would not create a new paradigm so much as inhibit research on the problem of emergence. The very idea is inconsistent with the fundamentals of science. Implied in Behe’s account of the analogy of biological systems to a mousetrap, just as for Paley’s to a watch, is the notion that organisms and their component parts either are artifacts, or are analogous to artifacts, or share some character with artifacts. Admittedly, Darwinians also use the language artifacts when describing the action of selection on particular structures to give apparent design (see for example Dawkins 1986; Maynard Smith 1995). But organisms have also been distinguished from artifacts ever since Aristotle wrote about the great difference between a house that had a designer and builder and an animal that is the product of a cycle of growth, development and reproduction, whose parts can be defined, come into being, and indeed only exist, in relation to the whole. Organisms are not assemblies of widgets. Although we can give a narrative of the development of technological artifacts in an evolutionary form (Basalla 1988), it is only an analogy in reverse, based upon variation of design and selection by the market place. A hammer, to use one of Basalla’s examples, is constructed; it does not start as a “hammer monad” that assimilates nutrients, thereby driving it to a state far from equilibrium under a gradient of matter/energy. Nor does it make its internal components, grow, divide, differentiate, and develop according to an epigenetic program. Variations in hammer design are not the result of changes in internal directions or in the process of development. “Generations” of hammers do not form a lineage of reproductive descent. What is true for hammers is true for mousetraps. Behe concedes that artifacts are a weak analogy to organisms in view of the fact that artifacts and organisms have different conditions of decomposition. But he claims that the part of an artifact’s character that provides a robust analogy is that of irreducible complexity. Behe says that we need to infer to the best argument. Since there are only two possible ways to deal with irreducible complexity, Behe argues, if the selectionist account is lacking then intelligent design is demonstrated. But the supposed intractability of irreducible complexity may well be prematurely assumed for natural systems, as I have tried to suggest above. Further, the fact that organisms arise through a developmental process in which components

602 needed for subsequent stages are brought into being during earlier stages, suggests that there can be mutually entailing roles for chance, selection and self-organization. Any attempt to understand the emergence of complexity must address the reality of development. It has been clear for some time that evolution at the molecular level as represented by structural gene products reflects only part of the important phenomena and mechanisms for evolution. Point mutations, insertions and deletions in individual genes (information used for producing phylogenetic diagrams) that could allow fine tuning of the biological function of the gene product, as well as neutral drift, and the phenomena of gene duplication and exon shuffling can generate new biological functions at the molecular level. Much of what has from this perspective been called “junk” DNA may play a role in the regulation of development. Differences in DNA sequence between closely related species, such as man and chimpanzee, can be quite small, on the order of a few percent, even though there are major differences in morphology and behavior. For over two decades it has been clear that the significant molecular changes responsible for such morphological difference do not occur in the structural genes coding for proteins or small RNA molecules but rather in the genes coding for the regulation of development (Wilson, Carlson and White 1977). It can take remarkably few genetic changes to produce major morphological changes. For example, it is estimated that as few as a half dozen or so mutations in regulatory genes affecting development could have made a grass into the ancestor of corn (Culotta 1991). A given trait or complex structure might arise from a rather small number of changes in organization of the developmental genes, taking advantage of duplicated and divergent genes that may have arisen by neutral or self-organizational processes. Developmental biology is being transformed by molecular genetics, and problems for evolutionary biology that might seem intractable to Behe, or indeed many others, may soon be tractable (Gilbert 1991, 1997; Hall 1992; Raff 1996; Gerhart and Kirschner 1997; Gordon 1998). A number of ways in which developmental biology might inform evolutionary theories lie outside of the Darwinian Research Tradition (see for example Salthe 1993; Webster and Goodwin 1996). One new approach, however, that may be compatible with Darwinism is Developmental Systems Theory. This approach, which emphasizes the role of the entire organism’s life cycle on the developmental pattern (Gray 1992; Oyama 1992; Griffiths and Gray 1994), shares at least some conceptual territory with the complexsystem dynamic approach to evolution in a mutually illuminating manner (Weber and Depew 1998). There are a number of ways that the full integration of developmental biology with evolutionary theory is being currently explored. Behe is silent

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