james barham university of notre dame & institute for the study of nature june 18, 2009

James Barham University of Notre Dame & Institute for the Study of Nature June 18, 2009

Goals of This Lecture To argue that: There is a Life/Body Problem analogous to the Mind/Body Problem Contemporary work in nonlinear dynamics and condensed-matter physics may offer a way of understanding the Life/Body Problem in terms of the emergence of a living phase of matter

Claim: Just as there is a widely acknowledged problem relating mind to its material substrate (the brain), so too is there a real problem relating life to its material substrate (the membranes, organelles, enzymes, etc. constituting the cell).

What the Problem Is It looks like living things possess something like preferences (values) and goals (purposes) as an organizing principle Neutrophil phagocytosis http://www.youtube.com/watch?v=fpOxgAU5fFQ Modern biological science claims to give an exhaustive account of life without reference to value or purpose If modern biology is right, there is no value or purpose in life as such Still leaves possibility of emergence higher up But if the intuition that life as such involves value and purpose is right, then our scientific account is incomplete Natural science option? Here, I will argue that our scientific account of life is incomplete

Current Account 1 There is no essence of life Just a list of more or less general properties: Metabolism Growth Responsiveness to stimuli Reproduction Ability to evolve Etc.

Current Account 2 Cells are machines Like automobiles and computers All of the parts of the cell (phenotype) are generated mechanically by the genotype (DNA) Central Dogma: DNA RNA Proteins DNA carries the information for the cell The machinery of the cell is regulated by feedback mechanisms (cybernetic control)

Conventional Account 3 The complex machinery of the cell was put into place gradually by Natural Selection Random genetic mutation New parts of the cell machinery come into being by chance Survival of the fittest If a new part just happens to increase a cells probability of survival and reproduction relative to competing cells in a population, then gradually cells containing that part will come to dominate the population

Challenging the Current Account I will argue that many aspects of the Current Account are mistaken: Life does have an essential nature I call the essential nature of life functional stability Cells are categorially different from manmade machines Machines are not functionally stable in the way that cells are Cell regulation is not fully explained by cybernetic control theory Natural selection cannot explain the deep conceptual problems with life The Central Dogma is probably wrong (Jablonka & Raz 2009; Shapiro forthcoming) Even if genotypic change were mostly random, phenotype construction is clearly goal-directed ( West-Eberhard 2003; 2005), so phenotype variation is not random

The Big Problem There is one big problem underlying all the other problems with the Current Account of life Non-living things (e.g., mountains) may endure for long periods of time But living things manipulate matter selectively, drawing on internal energy stores, in order to endure In short, living systems have an intrinsic preferred state : namely, self-preservation (token or type) Ordinary physical principles by themselves (e.g., free energy minimization) cannot explain this fact I will argue that neither cybernetic control theory nor selection theory helps

The Essence of the Big Problem There are many ways to express the nature of the Life/Body Problem The essence of the problem seems to me to be to give some sort of scientific account of a set of interlocking conceptual features of life and action: Value Purpose Instrumental Ought I call this the Normative Nexus

The Normative Nexus Living things seem to prefer existence over non-existence This preference creates value distinctions Whatever contributes to self-preservation is good; whatever hinders self- preservation is bad Living things must act in order to maintain themselves in existence Action occurs according to means-end logic Action strives towards particular ends or goals (is inherently purposive) Actions may or may not succeed (attain their purpose) To succeed, the means chosen must be appropriate to the end Thus, life operates under the hypothetical imperative (or instrumental ought) If you want to achieve X, then you ought to do Y This set of interlocking phenomena value, purpose (or teleology), and instrumental ought (or normativity) may be called the Normative Nexus

The Big Objection But there is a big objection to this view: Sure, we all talk about life as though it operated according to the Normative Nexus See almost any page of any textbook But most scientists believe that is just a metaphor, a convenience, a faon de parler After all, we already have a perfectly good theoretical framework in place that reduces normativity Dont we?

Reducing Normativity The Current View claims to reduce normativity in two basic ways Cybernetic control theory explains how it is possible for organisms to behave in an apparently goal-directed way The theory of natural selection explains how cybernetic control systems come to exist naturally

Cybernetic Control Begs the Question The purpose of a thermostat-furnace system is to maintain ones house at a certain temperature This purpose is attained thanks to a particular organization Call this particular organization good-repair Good-repair is imposed on the system by us We determine which organization counts as good-repair There is no principle internal to the system that causes either the thermostat or the furnace to preserve itself in good-repair Good-repair maintained via rigidity of parts Thermostats and furnaces do not prefer the state of good-repair Conclusion: The concept of cybernetic control begs the question of normativity Ditto for the concept of information in biology

Selection Theory Also Begs the Question Before new organic form can be selected, first it must exist Natural selection creates nothing; it amplifies what already exists Functional organization of organism is always already assumed to exist by the logic of selection theory Furthermore, even if the Central Dogma is true, any random change at the level of genotype must still be constructed into a phenotype This construction means functionally integrating the new part into the existing organization of the cell Conclusion: The principle of natural selection begs the question of normativity

Positive Evidence Needed Even if it is true that cybernetic control and selection theories do not fully reduce normativity Still, it would be nice if there were some positive evidence in favor of my claim that the Normative Nexus is something objectively real There is

Metastability of Life Consider the following facts: Living things are capable of recovering their dynamical equilibrium following perturbation to some extent (robustness) Developmental trajectories Wound repair Living things are capable of finding entirely new dynamical equilibria following perturbation (plasticity) Slijpers goat and friends Let us call robustness and plasticity together by the name bio- metastability Bio-metastability is a normative concept Presupposes a preferred state of the organism However, we still need proof that natural selection cannot explain all the specific forms of bio-metastability

Slijpers Goat and Friends West-Eberhard (2003, 2005) describes the case of Slijpers goat Here is a very similar case we can see with our own eyes: Faith the Dog: http://www.youtube.com/watch?v=aZsV4R3XJKk http://www.youtube.com/watch?v=aZsV4R3XJKk Other examples: Martin Heisenbergs flies (Heisenberg & Wolf 1984; 194204) Mriganka Surs ferrets (Sharma et al. 2000) Note that: All these examples exemplify the Normative Nexus Natural Selection cannot possibly explain them

The Point of the Examples Conclusions: Most living behavior is dynamically constructed by the organism interacting with the environment (Jirsa & Kelso 2004; Juarrero 1999; Warren 2006) Behavioral plasticity implies anatomical/physiological plasticity Plasticity is an intrinsic property of living systems as such Plasticity (or, more generally, Bio-Metastability) exemplifies the Normative Nexus The Normative Nexus is an aspect of Lifes essential nature

Need for a Unifying Physical Principle All of this leads to a further conclusion: There must be a unifying physical principle underlying the functional activity of living systems Here is a brief argument leading to the same conclusion: All enduring natural physical systems are governed by an underlying stability principle (together with constraints) Cells are enduring natural physical systems Therefore, cells are governed by an underlying stability principle

Functional Stability Principle What can we say about this principle? The most important thing to recognize is that it is distinct from ordinary physical principles operating at the macroscopic level, which at bottom boil down to free energy minimization The stability principle underlying life is different Living stability is achieved by means of the coordination of functional actions Let us call this principle functional stability

What Ive Tried to Show So Far The chief properties of life that distinguish cells and other organisms from inanimate matter are: Normative Nexus Bio-Metastability These properties are objectively real, and require scientific explanation They cannot be explained by either cybernetic control or selection theory (because both theories presuppose preferred states) To explain them, we need to posit the existence of an underlying principle of functional stability The principle of functional stability provides us with an essence of life and a solution to the Life/Body problem But what is the principle of functional stability, from a physical point of view?

Claim: Life may be a manifestation of a particular kind of condensed matter (the living phase of matter), and, if so, then it may be explainable via a particular conception of emergence.

The Problem with Microphysical Reduction Scientists often show why a thing, N, has the properties or causal powers that it does by showing how Ns parts, M 1, M 2, M j, work together to produce N Call this microphysical reduction Microphysical reduction seems to show that the apparent causal powers of N have been shown actually to reside in its parts Baseball example Causal power has drained away from level N to level M But it is plausible to think that what is real has causal powers Alexanders dictum So, if level N has no causal powers of its own, it seems justified to deny that is real So, N can be eliminated from our scientific world picture But the same procedure can be repeated for level M, as well; etc. So, nothing is real except the fundamental level (quarks, or whatever)

Eliminativism vs. Emergence Someone who cheerfully accepts this argument is called an Eliminativist To most folks, though, the conclusion that nothing is real but quarks seems absurd The question is: How should we understand the relationship between a thing and the parts that comprise it? The Emergentist replies: Some kinds of wholes are just the sum of their parts Other kinds of wholes have causal powers that are not merely the sum of the contributions of their parts

Definition of Emergence So, the doctrine of emergence is basically just the denial of eliminativism It says: For some kinds of wholes, the whole (level N) has causal powers above and beyond what is contributed by all of the individual parts (level M) But this idea has conceptual problems of its own

The Problem with Emergence Traditionally, there have two been kinds of objections to emergence: N-level causal powers seem inexplicable Brute fact, magic, pixie dust, etc. N-level causal powers imply downward causation, which many find incoherent Downward causation means: N-level causally affects M-level But how can N-level causally affect M-level when M-level is required to produce N-level in the first place? Margaret Morrisons (2006) theoretical principles view of emergence provides answers to both objections

Answering the Brute Fact Objection Morrrison (2006) points to what she calls theoretical principles that are used to explain how stable states of matter can exist and yet be insensitive to the details of the lower-level dynamics Spontaneous symmetry breaking Renormalization Group Critical phenomena (phase transitions, etc.) Effective field theories She writes (ibid.; 882) : The relation to higher level theoretical principles like symmetry breaking and localization shows that certain kinds of stable behavior, though not derivable from fundamental theory, can nevertheless be explained in a systematic way, one that doesnt rely on the contingencies of particular situations. On this account, emergent properties not just a brute fact

Answering the Downward Causation Objection Morrison (ibid.; 883) also mentions the way in which phonons are produced as a collective feature of a large number of atoms condensed into a crystal The N-level (crystal) has properties (phonons) that the M-level (atoms) lack She does not put it like this, but it is clear from the example that causation is the wrong way to think about the relation between M-level and N-level It is not that the atoms make individual contributions to the causal powers of the crystal Rather, the atoms collectively constitute a different kind of entity with new causal powers On this view, constitution, not causation, is the correct relation between M-level and N-level In that case, downward causation of N-level onto M-level is logically consistent

Emergence and Life One last question remains: How can we apply the theoretical principles view of emergence to the living phase of matter? Is such an idea even remotely plausible, from an empirical point of view?

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 Morrisons theoretical- principles-based emergence may be involved in the living phase of matter

Conclusion This statement by the Japanese systems biologist, Hiroaki Kitano (2007; 3), nicely summarizes 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 If such a formalism could be found, then a rigorous theory of functional stability might be possible The best hope for this would seem to lie in extending the theoretical principles of condensed-matter physics to encompass the living phase of matter In that case, a solution to the Life/Body Problem on the basis of emergence would be within reach

Frauenfelder, Hans, Peter G. Wolynes, and Robert H. Austin (1999) Biological Physics, Reviews of Modern Physics 71 (special issue): S419S430. 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: 51295134. 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: 131176.

References (cont.) Jirsa, V.K. and J.A.S. Kelso, eds. (2004) Coordination Dynamics: Issues and Trends. Berlin: Springer. Juarrero, Alicia (1999) Dynamics in Action: Intentional Behavior as a Complex System. Cambridge, MA: Bradford Books/MIT Press. Kitano, Hiroaki (2007) Towards a Theory of Biological Robustness, Molecular Systems Biology 3: article number 137. 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. 189221. Morrison, Margaret (2006) Emergence, Reduction, and Theoretical Principles: Rethinking Fundamentalism, Philosophy of Science 73: 876887. 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. Shapiro, James A. (forthcoming) Revisiting the Central Dogma in the 21 st Century. (available online)

References (cont.) Sharma, J., A. Angelucci, and M. Sur (2000) Induction of Visual Orientation Modules in Auditory Cortex, Nature 404: 841847. Warren, William H. (2006) The Dynamics of Perception and Action, Psychological Review 113: 358389. 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: 610618. 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: 19951961.

james barham university of notre dame & institute for the study of nature june 18, 2009

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scientific account of

exhaustive account of

random slide

essence of life

incomplete slide

conventional account

big problem

cell machinery