The Normative Nexus and the Nature of Functional Stability

1. The Normative Nexus and the Nature of Functional Stability James Barham University of Notre Dame ISHPSSB Brisbane, Australia July 14, 2009

2. Teleology Is Back • Remarkably, it has recently become almost respectable to argue that a proper understanding of human beings requires taking teleology seriously • Not just in human thought and action, but in biology generally • Foot (2001), MacIntyre (2006), McLaughlin (2001), Nagel (forthcoming), Okrent (2007), Schueler (2003), Sehon (2005), E. Thompson (2007), M. Thompson (2008), Walsh (2006), Weber & Varela (2002), Zammito (2006) • Of course, the first thing one might ask about this claim is what it means to “take teleology seriously”

3. Taking Teleology Seriously? • Epistemological Approach • Teleological explanation in biology is non-optional, • But this tells us more about the peculiarities of human cognition than it does about life as such • “Disunity-of-Science” Approach • Unity of science is a chimera; many different forms of explanation flourish independently • Teleological explanation in biology is just one of these • Realist Approach • Teleological explanation in biology is non-optional, • Because it corresponds to an objectively real, physical principle

4. What Teleological Realism in Biology Means • Realism about teleology in biology essentially means: • The explananda corresponding to teleological explanations enjoy metaphysical parity with those corresponding to mechanistic explanations (Walsh forthcoming) • In other words, realism about teleology in biology is the claim that: • Teleology is not just an explanatory principle • There is also a corresponding metaphysical principle that ought to be investigated as an explanandumin its own right

5. Assuming the Realist Approach • In this talk, I will assume the realist approach • I will not argue for its superiority over the other two main approaches • However, I acknowledge that the realist approach is the most controversial one, with the heaviest burden of proof • Two main aims of this talk: • To motivate a particular characterization of teleology in biology • To argue for the plausibility of this characterization

6. Teleology and Consciousness • I will ask you to take one more assumption for granted: • Although our paradigm of purposiveness is human conscious action, nevertheless, the purposiveness of human action and its conscious, subjective, or experiential quality are conceptually distinct • See Bedau (1990) • Therefore, the teleological phenomena associated with life as such may or may not beessentially linked to consciousness, as a matter of nomological fact • Here, I will simply bracket the question • When I speak of teleology in biology, no assumption of accompanying subjective experience ought to be inferred

7. Is There a Normative Survival Principle? • At the heart of the realist approach to teleology in biology is the claim: • Biological “survival”* is a normative concept; therefore, on the assumption of realism, there exists some real physical principle corresponding to the normativity of biological survival • Let us look at some arguments pro and contra this highly controversial claim • Note: The notion of “survival” as I use it here encompasses both metabolism–the functional organization ensuring the perpetuation of the token physical system–and reproduction–the process (which is itself a particular instance of metabolism) ensuring the perpetuation of the type physical system.

8. Arguments Pro a Normative Survival Principle • It certainly seems as though survival were a normative concept • Colloquial function talk • Feeding, fleeing, fighting, reproducing, “struggle” for survival, etc. • Biological talk • Goals, purposes, functions, information, messages, signals, codes, computing, proofreading, editing, etc. (see any textbook) • Increasing use of term intelligence • Capacity to choose appropriate means to an end • Bray (2009), Jonker et al. (2002), Shapiro (2007) • All of these ways of describing biological phenomena are normative • They all imply a standard of success/failure, correctness/error, etc. • Ultimately, they all presuppose the normativity of survival

9. Lowe’s Analysis of Action • In addition, it is striking that many conceptual analyses of human action may be applied more or less without alteration to living processes as such • Consider, for example, E.J. Lowe’s analysis of practical action, in the broad sense of instrumental rationality: • “Just as a true belief is one which corresponds to fact, so a good action is one which corresponds to need. In another idiom, just as facts are the truth-makers of true beliefs, so needs are the goodness-makers of good actions.” (Lowe 2008; 209; original emphasis)

10. Survival and Needs • Obviously, the concept of “needs” in Lowe’s account is itself in need of further analysis • Lowe postpones that question, but says he “holds out no hope” that a naturalistic account of need can succeed (Lowe 2008; 212) • For our purposes, “needs” may be understood in relation to survival • A dog has need of water in order to survive; thus, drinking water is a good for the dog because it contributes to its survival • What is important is to see that conceptual analyses of human instrumental rationality are directly applicable to living processes as such • I will pursue this idea further in a moment • But first let us begin the task of looking at the notion of survival from a physical point of view

11. Survival as Dynamic Stability • A living thing is a physical system of the nonequilibrium-thermodyamic (“dynamic”) type • Hurricanes, candle flames, other “dissipative structures” • For a living system to “survive” is for it to persist as the kind of dynamic physical system that it is • With a lifespan that is long compared to its thermodynamic relaxation rate • For any sort of physical system to persist is for it possess a sort of stability • For a dynamic system to persist is for it to possess a type of dynamic stability • Therefore, a living system possesses a type of dynamic stability

12. The Notion of Functional Stability • However, the type of dynamic stability possessed by a living system is different from that possessed by any non-living system • The latter always boils down to free energy minimization • In contrast, living systems draw on internal energy stores to act on the world to satisfy their needs • The type of dynamic stability possessed by living systems implies the concept of action • Individual goal-directed actions may be termed “functions” • Therefore, we may call the type of dynamic stability possessed by living systems functional stability

13. The Normative Nexus • Survival is ultimately normative for living systems • Normativity of survival implies ultimate goal-state (purpose) to be aimed at • Call it “Z” • Survival (functional stability) cannot be achieved without specific actions (functions) • Action-requirement implies needs (such as drinking water) • Call it “X” • Needs imply means-end relation and hypothetical necessity • X is needed (required) for Z • Hypothetical necessity implies instrumental “ought” • If Z is to obtain, then Xought to occur • Needs and means-end relation give rise to value (à la Lowe) • X is good in case it contributes to Z • Drinking water is good (e.g., for a dog) in case it contributes to survival • Call this web of relations among survival, action, purpose, need, instrumental ought, and value, the Normative Nexus • This analysis works equally well at any level of the functional hierarchy

14. Example: Bacterial Chemotaxis • For example, take bacterial chemotaxis(Stock & Surette 1996) • An E. coli bacterium transitions between two motility states, “running” and “tumbling” • Running is smooth, linear motion produced by turning the flagella counterclockwise • Tumbling is random motion produced by turning the flagella clockwise • When a cell senses it is moving up an attractant (or down a repellant) gradient, it reduces the rate of tumbling, resulting in net movement towards (or away from) the source • It is quite natural to say: • A bacterium needs attractants (typically, a food source) to survive • Similarly, it needs to avoid repellants (typically, poison) to survive • Its purpose in swimming up (or down) a gradient is to find and consume attractants (or avoid repellants) • The flagellar mechanism is the means to this end • A bacterium ought to move toward attractant and away from repellant sources • Moving up an attractant (or down a repellant) gradient is good for a bacterium • All of this presupposes that bacteria can distinguish attractants from repellants • Bacteria partition their world into axiologicalcategories: • “Yum” and “yuck” (Kauffman et al. 2008)

15. Arguments Contra a Normative Survival Principle • Incredulous stare • The Normative Nexus is just anthropomorphic projection • It trades on equivocation • “Normativity” is properly attributable only to human reason • Survival, properly understood, is not a normative concept • Organisms are simply machines whose parts were put into place by natural selection • By accident, some organisms happen to attain novel configurations of their parts that happen to result in differential reproduction • Call this the “Reduction Claim” • “Functional stability” does not correspond to any single physical principle, but is only a congeries of disparate physical and chemical processes • A normative survival principle is inconsistent with everything we know about biology and physics • Call this the “Science Objection”

16. Reply to Incredulous Stare • The charges of anthropomorphism and equivocation essentially beg the question • Whether normativity is properly attributable to survival and other living processes is the issue • Besides, the Normative Nexus analysis works • Normative language makes perfect sense applied even to bacteria • Indeed, it is indispensable • It is virtually impossible to avoid normative language in biology • Why would this be the case, if the Normative Nexus were nothing more than an equivocation? • But what about the Reduction Claim?

17. Reply to Reduction Claim • To repeat: the Reduction Claim is that we already have a successful mechanistic reduction of teleology and normativity in biology • Namely, we know that organisms are simply machines put into place by natural selection • Three ways of replying: • Argument from History • Argument from Petitio • Argument from Extreme Plasticity

18. Argument from History • History (in this case, selection history) is not the right kindof concept to explain a dynamical property like functional stability • To speak of the “history” of a physical system is a short-hand way of referring to the sequence of states it traverses • But it is the dynamics of the system and surround that explain this sequence, not the other way around • Examples: amorphous solids (glass) vs. crystals, stars • In one sense, they are history-dependent • But that just means they are dependent on the particular details of their dynamical evolution

19. Argument from Petitio • It has been pointed out repeatedly that the theory of natural selection presupposes the functional organization of organisms, and so cannot explain it • A functionally coherent organism must already exist before it can be selected • See, e.g., McLaughlin (2001), Walsh (2000, 2007) • It is equally well-known that the concept of a machine also begs the question of normativity • “Machine” is a normative concept • A machine is something that performs a function • But nothing in the concept of a machine is capable of explaining which system state counts as the functional state • See, e.g., Nissen (1997)

20. A Recent Elaboration of the Petitio Argument • Recently, West-Eberhard(2003, 2005) has further refined the Petitio Argument • Even if genetic changes are always random,* phenotypic changes never are • Because between the genotype and the phenotype is the teleological process of phenotype construction • Therefore, whatever is subject to natural selection has already been teleologically constructed • This is a general point about all living things • However, it is powerfully demonstrated by examples of extreme plasticity • *Note: This now seems questionable (Jablonka & Raz 2009; Shapiro forthcoming), but there is no time to discuss this issue here

21. A Note on Terminology • The phenomenon in question goes by many different names: • Robustness, plasticity, adaptive capability, phenotypic accommodation, etc. • Terminology inconsistent • The basic idea is spontaneous compensation following perturbation to maintain viability • Two ways: • Recovery of old steady state (“robustness”) • Homeostasis, healing • Attainment of new steady state (“plasticity”) • Three-legged dog’s gait • A term to encompass both is “metastability” • Equifinality • Bifurcation

22. Examples of Extreme Plasticity • Cases of successful compensation following massive perturbation of: • visual system • in humans (Bach-y-Rita 1995; Ptito et al. 2005) • in mice & ferrets (Tropea et al. 2009; Von Melchner et al. 2000) • in flies (Heisenberg & Wolf 1984) • locomotory system • Slijper’s goat (West-Eberhard 2003, 2005) • Involves extensive remodeling of neural, skeletal, and muscular systems • single cells • Adaptation in isolated hepatocytes (Baker et al. 2001; Elaut et al. 2006) • These capacities are inexplicable on mainstream view • These specific capacities cannot possibly have been selected for • Positing selection for such a general capacity would concede the point at issue: • Life as such has a universal capacity for goal-directed compensation (metastability)

23. Reply to Science Objection • The Science Objectionsays: • A normative survival principle is inconsistent with everything we know about biology and physics • Three ways of replying: • A simple argument to show that a stability principle for living things should be expected • System-level models of cooperative phenomena in biology • Theoretical proposals for a normative survival principle • Together, these responses show that the existence of a normative survival principle is not implausible in light of contemporary science

24. A Stability Principle Should Be Expected • The following simple argument shows that we should expect there to be a physical principle underlying the functional stability of living things: • All naturally stable systems derive their stability from an underlying physical principle • Organisms are naturally stable systems • Therefore, organisms derive their stability from an underlying physical principle • The idea that organisms lack any unifying principle is highly suspect, from a physical point of view

25. System-Level Models of Cooperative Phenomena in Biology • Following are some system-level models of cooperative phenomena (long-range coherence and coordination) in biology • Brain Function (Freeman 2001; Freeman & Vitiello 2006) • Motor coordination (Jirsa & Kelso 2004; Kelso 1995; Warren 2006) • Cancer as a tissue-level disorder (Sonnenschein & Soto 1999) • Metabolic networks (Barabasi & Oltvai 2004; Csete & Doyle 2004; Wolkenhauer et al. 2005) • Coordination of muscle contraction (Pollack 2001)

26. Two Theoretical Proposals • Two specific theoretical proposals have been made for modeling a normative survival principle • Christensen & Bickhard(2002) • Di Paolo (2005) • Both of these proposals involve cashing out the notion of “autopoiesis” (self-production) in terms of nonlinear dynamics • This is surely a step in the right direction • However, while something like these proposals may be necessary for understanding a normative survival principle, they are not sufficient

27. The Trouble with Nonlinear Dynamical Models • No theoretical proposals drawing on nonlinear dynamics alone can be sufficient for modeling a truly normative survival principle • Nonlinear dynamical models as such are phenomenological • We need to connect them up with underlying physical principles • Adding nonequilibrium thermodynamics into the equation does not help, either • Dissipative structures still just minimize free energy • We need a way to distinguish functional stability from hurricanes, candle flames, etc.

28. A Way Forward • Morrison’s (2006) version of “emergence”* may offer a way forward • She points to what she calls theoretical principles that are used to explain how stable states of matter can exist and yet be autonomous (in the sense of insensitive to the details of the lower-level dynamics) • Spontaneous symmetry breaking • Renormalization Group • Critical phenomena (phase transitions, etc.) • Effective field theories • But why should we think that any of this is relevant to biology? • *Note: The notion of emergence is many-faceted and controversial; however, the main objection that any strong (ontological) version of emergence must violate Kim’s “causal exclusion principle” has been persuasively rebutted by Perovic (2007).

29. Aspects of the Living Phase of Matter • Cytoplasm has the following characteristics: • Extreme crowding (Luby-Phelps 2000; Wheatley 2003) • Gel-like properties (Pollack 2001) • Liquid-crystal-like properties (Ho et al. 1996) • Phase transitions important to macromolecular function (Pollack 2001; Pollack & Chin 2008) • In addition, proteins are: • Dynamically active (frustrated) systems (Frauenfelder et al. 1999) • Functionally coupled to the cytoplasm (Frauenfelder et al. 2009) • These facts support the idea that Morrison’s theoretical-principles-based emergence may be involved in the living phase of matter

30. The Nature of Functional Stability • The idea, then, is that the universal theoretical principles would provide some continuity across emergent levels • Example: spontaneous symmetry breaking • While a new particular law and/or conservation principle would come into existence with each new type of existent • Life would require its own conservation principle corresponding to the property of functional metastability • This statement by Hiroaki Kitano nicely expresses what is needed: • “The key issue is whether it is possible to find a formalism in which robustness and its trade-offs could be defined so that robustness is a conserved quantity” (Kitano 2007; 3; emphasis added)

31. Normative Survival Principle Not Unscientific • If such a formalism could be found, then a rigorous theoretical explanation of the normative survival principle might be possible • Because the functional metastability of life would be based on its own conservation principle, this proposal would not be tantamount to reducing life to another principle, like the conservation of energy • Given what we know about biology and physics, the existence of an emergent principle governing the sui generis functional dynamics of the living phase of matter is not out of the question (Laughlin et al. 2000) • The very existence of such theoretical proposals shows that the idea of a normative survival principle is not absurd or inconceivable

32. Conclusion • Extending theoretical principles derived from fundamental and condensed-matter physics to encompass the living phase of matterseems to offer the best hope of giving an adequate scientific account of the normative nexus and the functional metastability of living things

33. References Bach-y-Rita, Paul (1995) Nonsynaptic Diffusion Neurotransmission and Late Brain Reorganization. New York: Demos Publications. Baker, Thomas K., Mark A. Carfagna, Hong Gao, Ernst R. Dow, Qingqin Li, George H. Searfoss, and Timothy P. Ryan (2001) “Temporal Gene Expression Analysis of Monolayer Cultured Rat Hepatocytes,” Chemical Research in Toxicology 14: 1218–1231. Barabasi, Albert-Laszlo and Zoltan N. Oltvai(2004) “Network Biology: Understanding the Cell’s Functional Organization,” Nature Reviews Genetics 5: 101–113. Bedau, Mark (1990) “Against Mentalism in Teleology,” American Philosophical Quarterly27: 61–70. Bray, Dennis (2009) Wetware: A Computer in Every Living Cell. New Haven: Yale University Press. Christensen, Wayne D. and Mark H. Bickhard(2002) “The Process Dynamics of Normative Function,” Monist85: 3–28. Csete, Marie and John Doyle (2004) “Bow Ties, Metabolism and Disease,” Trends in Biotechnology 22: 446–450. Di Paolo, Ezequiel A. (2005) “Autopoiesis, Adaptivity, Teleology, Agency,” Phenomenology and the Cognitive Sciences 4: 429–452.

34. References (cont.) • Elaut, Greetje, Tom Henkens, Peggy Papeleu, Sarah Snykers, Mathieu Vinken, Tamara Vanhaecke, and Vera Rogiers(2006) “Molecular Mechanisms Underlying the Dedifferentiation Process of Isolated Hepatocytes and Their Culture,” Current Drug Metabolism7: 629–660. • Foot, Philippa(2001) Natural Goodness. Oxford: Clarendon Press. • Frauenfelder, Hans, Peter G. Wolynes, and Robert H. Austin (1999) “Biological Physics,” Reviews of Modern Physics 71 (special issue): S419–S430. • Frauenfelder, Hans, Guo Chen, Joel Berendzen, Paul W. Fenimore, Helen Jansson, Benjamin H. McMahon, Izabela R. Stroe, Jan Swenson, and Robert D. Young (2009) “A Unified Model of Protein Dynamics,” Proceedings of the National Academy of Sciences, USA 106: 5129–5134. • Freeman, Walter J. (2001) How Brains Make Up Their Minds. New York: Columbia University Press. • Freeman, Walter J. and Giuseppe Vitiello(2006) “Nonlinear Brain Dynamics as Macroscopic Manifestation of Underlying Many-Body Field Dynamics,” Physics of Life Reviews 3: 93–118. • Heisenberg, M. and R. Wolf (1984) Vision in Drosophila: Genetics of Microbehavior. Berlin: Springer. • Ho, Mae-Wan, J. Haffegee, R. Newton, Y.-M. Zhou, J.S. Bolton, and S. Ross (1996) “Organisms as Polyphasic Liquid Crystals,” Bioelectrochemistry and Bioenergetics 41: 81–91. • Jablonka , Eva and Gal Raz(2009) “Transgenerational Epigenetic Inheritance: Prevalence, Mechanisms, and Implications for the Study of Heredity and Evolution,” Quarterly Review of Biology 84: 131–176.

35. References (cont.) • Jirsa, V.K. and J.A.S. Kelso, eds. (2004) Coordination Dynamics: Issues and Trends. Berlin: Springer. • Jonker, Catholijn M., Jacky L. Snoep, Jan Treur, Hans V. Westerhoff, and Wouter C.A. Wijngaards (2002) “Putting Intentions into Cell Biochemistry: An Artificial Intelligence Perspective,” Journal of Theoretical Biology 214: 105–134. • Kauffman, Stuart, Robert K. Logan, Robert Este, Randy Goebel, David Hobill, and IlyaShmulevich(2008) “Propagating Organization: An Inquiry,” Biology and Philosophy 23: 27–45. • Kelso, J.A.S. (1995) Dynamic Patterns: The Self-Organization of Brain and Behavior. Cambridge, MA: Bradford Books/MIT Press. • Kitano, Hiroaki (2007) “Towards a Theory of Biological Robustness,” Molecular Systems Biology 3: article number 137. • Laughlin, R.B., D. Pines, J. Schmalian, B.P. Stojkovic, and P. Wolynes(2000) “The Middle Way,” Proceedings of the National Academy of Sciences 97: 32–37. • Lowe, E.J. (2008) Personal Agency: The Metaphysics of Mind and Action. Oxford: Oxford University Press. • Luby-Phelps, K. (2000) “Cytoarchitecture and Physical Properties of Cytoplasm: Volume, Viscosity, Diffusion, Intracellular Surface Area,” in H. Walter, D.E. Brooks, and P.A. Srere, eds., International Journal of Cytology, Vol. 192: Microcompartmentation and Phase Separation in Cytoplasm. San Diego: Academic Press, pp. 189–221.

36. References (cont.) • MacIntyre, Alasdair (2006) “What Is a Human Body?,” in idem, The Tasks of Philosophy: Selected Essays, Volume 1. Cambridge: Cambridge University Press, pp. 86–103. • McLaughlin, Peter (2001) What Functions Explain: Functional Explanation and Self-Reproducing Systems. Cambridge: Cambridge University Press. • Morrison, Margaret (2006) “Emergence, Reduction, and Theoretical Principles: Rethinking Fundamentalism,” Philosophy of Science 73: 876–887. • Nagel, Thomas (forthcoming) “Secular Philosophy and the Religious Temperament,” in idem, Secular Philosophy and the Religious Temperament: Essays 2002-2008. Oxford: Oxford University Press. http://records.viu.ca/www/ipp/pdf/2.pdf • Nissen, Lowell (1997) Teleological Language in the Life Sciences. Lanham, MD: Rowman & Littlefield. • Okrent, Mark (2007) Rational Animals: The Teleological Roots of Intentionality. Athens, OH: Ohio University Press. • Perovic, Slobodan (2007) “The Limitations of Kim’s Reductive Physicalism in Accounting for Living Systems and an Alternative Nonreductionist Ontology,” ActaBiotheoretica55: 243–267. • Pollack, Gerald H. (2001) Cells, Gels, and the Engines of Life. Seattle: Ebner & Sons. • Pollack, Gerald H. and Wei-Chun Chin, eds. (2008) Phase Transitions in Cell Biology. Berlin: Springer.

37. References (cont.) • Ptito, Maurice, Solvey M. Moesgaard, Albert Gjedde, and Ron Kupers(2005) “Cross-Modal Plasticity Revealed by Electrotactile Stimulation of the Tongue of the Congenitally Blind,” Brain128: 606–614. • Schueler, G.F. (2003) Reasons and Purposes: Human Rationality and the Teleological Explanation of Action. Oxford: Clarendon Press. • Sehon, Scott R. (2005) Teleological Realism: Mind, Agency, and Explanation. Cambridge, MA: Bradford Books/MIT Press. • Shapiro, James A. (2007) “Bacteria Are Small but Not Stupid: Cognition, Natural Genetic Engineering and Socio-Bacteriology,” Studies in History and Philosophy of Biological and Biomedical Sciences 38: 807–819. • Shapiro, James A. (forthcoming) “Revisiting the Central Dogma in the 21st Century,” Annals of the New York Academy of Sciences. http://shapiro.bsd.uchicago.edu/Shapiro2009.AnnNYAcadSciMS.RevisitingCentralDogma.pdf • Sonnenschein, C. and A.M. Soto (1999) The Society of Cells: Cancer and the Control of Cell Proliferation. Oxford/New York: Bios Scientific Publishers/Springer. • Stock, Jeffry B. and Michael G. Surette(1996) “Chemotaxis,” in Frederick C. Neidhardt, ed., Escherichia coli and Salmonella: Cellular and Molecular Biology, 2nd ed. Washington: ASM Press, vol. I, pp. 1103–1129. • Thompson, Evan (2007) Mind in Life: Biology, Phenomenology, and the Sciences of Mind. Cambridge, MA: Belknap Press/Harvard University Press.

38. References (cont.) • Thompson, Michael (2008) Life and Action: Elementary Structures of Practice and Practical Thought. Cambridge, MA: Harvard University Press. • Tropea, Daniela, Audra Van Wart, and Mriganka Sur (2009) “Molecular Mechanisms of Experience-Dependent Plasticity in Visual Cortex,” Philosophical Transactions of the Royal Society B 364: 341–355. • Von Melchner, L., S.L. Pallas, and M. Sur (2000) “Visual Behaviour Mediated by Retinal Projections Directed to the Auditory Pathway,” Nature404: 871–976. • Walsh, D.M. (2000) “Chasing Shadows: Natural Selection and Adaptation,” Studies in History and Philosophy of Biological and Biomedical Sciences31: 135–153. • Walsh, D.M. (2006) “Organisms as Natural Purposes: The Contemporary Evolutionary Perspective,” Studies in History and Philosophy of Biological and Biomedical Sciences37: 771–791. • Walsh, D.M. (2007) “The Pomp of Superfluous Causes: The Interpretation of Evolutionary Theory,” Philosophy of Science 74: 281–303. • Walsh, D.M. (forthcoming) “Mechanism, Emergence and Miscibility: The Autonomy of Evo-Devo.” • Warren, William H. (2006) “The Dynamics of Perception and Action,” Psychological Review113: 358–389. • Weber, Andreas and Francisco J. Varela (2002) “Life After Kant: Natural Purposes and the Autopoietic Foundations of Biological Individuality,” Phenomenology and the Cognitive Sciences1: 97–125.

39. References (cont.) • West-Eberhard, Mary Jane (2003) Developmental Plasticity and Evolution. Oxford: Oxford University Press. • West-Eberhand, May Jane (2005) “Phenotypic Accommodation: Adaptive Innovation Due to Developmental Plasticity,” Journal of Experimental Zoology B (Molecular and Developmental Evolution) 304B: 610–618. • Wheatley, D.N. (2003) “Diffusion, Perfusion and the Exclusion Principles in the Structural and Functional Organization of the Living Cell: Reappraisal of the Properties of the ‘Ground Substance,’” Journal of Experimental Biology 206: 1995–1961. • Wolkenhauer, Olaf, MukhtarUllah, Peter Wellstead, and Kwang-Hyun Cho (2005) “The Dynamic Systems Approach to Control and Regulation of Metabolic Networks,” FEBS Letters 579: 1846–1853. • Zammito, John (2006) “Teleology Then and Now: The Question of Kant’s Relevance for Contemporary Controversies over Function in Biology,” Studies in History and Philosophy of Biological and Biomedical Sciences37: 748–770.