Stuart Kauffman - Academia.edu (original) (raw)

Papers by Stuart Kauffman

Entropy, 2022

Random Boolean Networks (RBNs for short) are strongly simplified models of gene regulatory networ... more Random Boolean Networks (RBNs for short) are strongly simplified models of gene regulatory networks (GRNs), which have also been widely studied as abstract models of complex systems and have been used to simulate different phenomena. We define the “common sea” (CS) as the set of nodes that take the same value in all the attractors of a given network realization, and the “specific part” (SP) as the set of all the other nodes, and we study their properties in different ensembles, generated with different parameter values. Both the CS and of the SP can be composed of one or more weakly connected components, which are emergent intermediate-level structures. We show that the study of these sets provides very important information about the behavior of the model. The distribution of distances between attractors is also examined. Moreover, we show how the notion of a “common sea” of genes can be used to analyze data from single-cell experiments.

We approach the question “What is Consciousness?” in a new way, not as Descartes’ “systematic dou... more We approach the question “What is Consciousness?” in a new way, not as Descartes’ “systematic doubt”, but as how organisms find their way in their world. Finding one’s way involves finding possible uses of features of the world that might be beneficial or avoiding those that might be harmful. “Possible uses of X to accomplish Y” are “Affordances”. The number of uses of X is indefinite (or unknown), the different uses are unordered, are not listable, and are not deducible from one another. All biological adaptations are either affordances seized by heritable variation and selection or, far faster, by the organism acting in its world finding uses of X to accomplish Y. Based on this, we reach rather astonishing conclusions: (1) Artificial general intelligence based on universal Turing machines (UTMs) is not possible, since UTMs cannot “find” novel affordances. (2) Brain-mind is not purely classical physics for no classical physics system can be an analogue computer whose dynamical beha...

Our argument in Against Design may seem new, challenging, or even bizarre. One commenter, Levinso... more Our argument in Against Design may seem new, challenging, or even bizarre. One commenter, Levinson, questions whether we really mean what we say: “I presume that the authors cannot really be arguing that all design is impossible.”1 Given our admittedly unorthodox and perhaps radical challenge to common notions of design, we appreciate the thoughtful attention to our views given by our commenters Vernon Smith, Sanford Levinson and Steven G. Calabresi. Even when disagreeing with us, they have responded to Against Design with open minds

Strategic Management Journal, 2021

Research SummaryThe search for new resources is costly and difficult within the resource‐based vi... more Research SummaryThe search for new resources is costly and difficult within the resource‐based view. Because search is costly, a common prescription is for firms to focus on their endowments—the resources they already possess. However, is there a way for firms to somehow find value amongst the “vast reservoirs” of external resources? We review existing forms of resource search and then suggest an alternative. Extending arguments from biology, we develop the idea of a firm‐specific search image and highlight how search images can reveal resources not obvious to others. The search image notion speaks to how firms might uniquely identify dormant resources, even in seemingly efficient factor markets. We conclude with a discussion of how our arguments pertain to the resource‐based view and the origins of resources.Managerial SummaryHow do managers and entrepreneurs search, identify, and find assets and resources in relentlessly competitive markets? Existing arguments largely suggest that...

SSRN Electronic Journal, 2020

Where do new resources come from? We build on the premise that environments feature vast reservoi... more Where do new resources come from? We build on the premise that environments feature vast reservoirs of latent resources, uses and resource combinations. However, identifying this value can be costly and difficult. In this paper we consider the thought experiment of an endowment-less firm and how it might search for and develop latent resources. We build on perception science and evolutionary biology to highlight how the notion of “searching-for” foreshortens costly search processes. Contrarian beliefs offer a mechanism for generatively seeding search and bootstrapping resources and heterogeneity. Beliefs partially solve the factor markets problem; though their realization is dependent on developing firm-specific theories of value and targeted experimentation. Our approach also addresses how firms might actively harness the adjacent possible. We conclude with a discussion of how our arguments relate to fundamental questions in the field of strategy and the resource-based view.

SSRN Electronic Journal, 2019

In this paper we address the hard problem of search. Search is a pervasive phenomenon of biologic... more In this paper we address the hard problem of search. Search is a pervasive phenomenon of biological and economic life. But search is hard—especially in uncertain and dynamic environments. We develop a generalized form of question-answer probing as a way of simplifying search, with implications for understanding biological and economic novelty. This form of search simultaneously constrains and enables search spaces in counterintuitive ways. Question-answer probing not only illustrates seemingly mundane search activity (such as foraging for food or looking for a lost item), but it also provides the foundation for explaining the emergence of both evolutionary novelty and economic value. An organism’s (or organization’s) directed search (especially the search for function) supplies a key mechanism for realizing adjacent possibilities and new niches. Our approach contrasts with extant evolutionary and computational approaches to search (such as brute-force, serial processing or Bayesian priors and updating), which lack organism-specific mechanisms. Our approach also contrasts with physics-oriented conceptions of mind, organism and consciousness. Throughout the paper we offer cognitive, biological (e.g., tool making), and economic examples to illustrate our points. We conclude with a discussion of the implications of our arguments for economics and innovation.

Industrial and Corporate Change, 2016

In this article we challenge the notion of the efficiency of factor markets and provide an altern... more In this article we challenge the notion of the efficiency of factor markets and provide an alternative. We specifically identify both the environment-and actorrelated origins of heterogeneity in markets. We first discuss how environments have an exaptive nature, where new uses and possibilities emerge continuously and are poised for the taking. We then highlight how actor perceptions result in heterogeneous outcomes and how the identification of novel affordances-new uses or functions-for factors is a central origin of heterogeneity. We also discuss the existence of actor-and environment-related pressures toward homogeneity and seeming market efficiency. In conclusion we highlight the implications of our arguments for the strategy and innovation debate, and for our understanding of the nature of markets and economic activity.

Oncotarget, Jan 9, 2016

During a cell state transition, cells travel along trajectories in a gene expression state space.... more During a cell state transition, cells travel along trajectories in a gene expression state space. This dynamical systems framework complements the traditional concept of molecular pathways that drive cell phenotype switching. To expose the structure that hinders cancer cells from exiting robust proliferative state, we assessed the perturbation capacity of a drug library and identified 16 non-cytotoxic compounds that stimulate MCF7 breast cancer cells to exit from proliferative state to differentiated state. The transcriptome trajectories triggered by these drugs diverged, then converged. Chemical structures and drug targets of these compounds overlapped minimally. However, a network analysis of targeted pathways identified a core signaling pathway - indicating common stress-response and down-regulation of STAT1 before differentiation. This multi-trajectory analysis explores the cells' state transition with a multitude of perturbations in combination with traditional pathway anal...

Psychonomic Bulletin & Review, 2015

Dietrich and Haider (Psychonomic Bulletin & Review, 21 (5), 897-915, 2014) justify their integrat... more Dietrich and Haider (Psychonomic Bulletin & Review, 21 (5), 897-915, 2014) justify their integrative framework for creativity founded on evolutionary theory and prediction research on the grounds that Btheories and approaches guiding empirical research on creativity have not been supported by the neuroimaging evidence.^Although this justification is controversial, the general direction holds promise. This commentary clarifies points of disagreement and unresolved issues, and addresses mis-applications of evolutionary theory that lead the authors to adopt a Darwinian (versus Lamarckian) approach. To say that creativity is Darwinian is not to say that it consists of variation plus selectionin the everyday sense of the termas the authors imply; it is to say that evolution is occurring because selection is affecting the distribution of randomly generated heritable variation across generations. In creative thought the distribution of variants is not key, i.e., one is not inclined toward idea A because 60 % of one's candidate ideas are variants of A while only 40 % are variants of B; one is inclined toward whichever seems best. The authors concede that creative variation is partly directed; however, the greater the extent to which variants are generated non-randomly, the greater the extent to which the distribution of variants can reflect not selection but the initial generation bias. Since each thought in a creative process can alter the selective criteria against which the next is evaluated, there is no demarcation into generations as assumed in a Darwinian model. We address the authors' claim that reduced variability and individuality are more characteristic of Lamarckism than Darwinian evolution, and note that a Lamarckian approach to creativity has addressed the challenge of modeling the emergent features associated with insight.

Molecular BioSystems, 2015

Akin to biological networks, prebiotic chemical networks can evolve and we have identified six ke... more Akin to biological networks, prebiotic chemical networks can evolve and we have identified six key parameters that govern their evolution.

Progress in Biophysics and Molecular Biology, 2015

Attempts to 'naturalize' phenomenology challenge both traditional phenomenology and traditional a... more Attempts to 'naturalize' phenomenology challenge both traditional phenomenology and traditional approaches to cognitive science. They challenge Edmund Husserl's rejection of naturalism and his attempt to establish phenomenology as a foundational transcendental discipline, and they challenge efforts to explain cognition through mainstream science. While appearing to be a retreat from the bold claims made for phenomenology, it is really its triumph. Naturalized phenomenology is spearheading a successful challenge to the heritage of Cartesian dualism. This converges with the reaction against Cartesian thought within science itself. Descartes divided the universe between res cogitans, thinking substances, and res extensa, the mechanical world. The latter won with Newton and we have, in most of objective science since, literally lost our mind, hence our humanity. Despite Darwin, biologists remain children of Newton, and dream of a grand theory that is epistemologically complete and would allow lawful entailment of the evolution of the biosphere. This dream is no longer tenable. We now have to recognize that science and scientists are within and part of the world we are striving to comprehend, as proponents of endophysics have argued, and that physics, biology and mathematics have to be reconceived accordingly. Interpreting quantum mechanics from this perspective is shown to both illuminate conscious experience and reveal new paths for its further development. In biology we must now justify the use of the word "function". As we shall see, we cannot prestate the ever new biological functions that arise and constitute the very phase space of evolution. Hence, we cannot mathematize the detailed becoming of the biosphere, nor write differential equations for functional variables we do not know ahead of time, nor integrate those equations, so no laws "entail" evolution. The dream of a grand theory fails. In place of entailing laws, a post-entailing law explanatory framework is proposed in which Actuals arise in evolution that constitute new boundary conditions that are enabling constraints that create new, typically unprestatable, Adjacent Possible opportunities for further evolution, in which new Actuals arise, in a persistent becoming. Evolution flows into a typically unprestatable succession of Adjacent Possibles. Given the concept of function, the concept of functional closure of an organism making a living in its world, becomes central. Implications for patterns in evolution include historical reconstruction, and statistical laws such as the distribution of extinction events, or species per genus, and the use of formal cause, not efficient cause, laws.

Biological Information, 2013

It is argued that no law entails the evolution of the biosphere. Biological evolution rests on bo... more It is argued that no law entails the evolution of the biosphere. Biological evolution rests on both quantum random and classical non-random natural selection and whole-part interactions that render the sample space of adjacent biological possibilities unknowable. This would seem to create an insurmountable problem for intelligent design in biology. Nonetheless, the evolution of ensembles of interacting systems can be modeled by statistical laws that have strong self-organizational properties. Some compelling examples modeling evolutionary self-organization in biology are presented and it is concluded that a new science of order and organization beyond entailing law is required.

Life, 2011

I discuss briefly the history of the origin of life field, focusing on the "Miller" era of prebio... more I discuss briefly the history of the origin of life field, focusing on the "Miller" era of prebiotic synthesis, through the "Orgel" era seeking enzyme free template replication of single stranded RNA or similar polynucleotides, to the RNA world era with one of its foci on a ribozyme with the capacity to act as a polymerase able to copy itself. I give the history of the independent invention in 1971 by T. Ganti, M. Eigen and myself of three alternative theories of the origin of molecular replication: the Chemotron, the Hypercycle, and Collectively Autocatalytic Sets, CAS, respectively. To date, only collectively autocatalytic DNA, RNA, and peptide sets have achieved molecular reproduction of polymers. Theoretical work and experimental work on CAS both support their plausibility as models of openly evolvable protocells, if housed in dividing compartments such as dividing liposomes. My own further hypothesis beyond that of CAS in themselves, of their formation as a phase transition in complex chemical reaction systems of substrates, reactions and products, where the molecules in the system are candidates to catalyze the very same reactions, now firmly established as theorems, awaits experimental proof using combinatorial chemistry to make libraries of stochastic DNA, RNA and/or polypeptides, or other classes of molecules to test the hypothesis that molecular polymer reproduction has emerged as a true phase transition in complex chemical reaction systems. I remark that my colleague Marc Ballivet of the University of Geneva and I, may have issued the first publications discussing what became combinatorial chemistry, in published issued patents in 1987, 1989 and later, in this field.

Scientific American, 1991

Biological evolution may have been shaped by more than just natural selection. Computer models su... more Biological evolution may have been shaped by more than just natural selection. Computer models suggest that certain complex systems tend toward self-organization M athematical discoveries are in viting changes in biologists' thinking about the origins of order in evolution. All living things are highly ordered systems: they have intri cate structures that are maintained and even duplicated through a precise bal let of chemical and behavioral activi ties. Since Darwin, biologists have seen natural selection as virtually the sole source of that order. But Darwin could not have suspected the existence of self-organization, a re cently discovered, innate property of some complex systems. It is possible that biological order reflects in part a spontaneous order on which selection has acted. Selection has molded, but was not compelled to invent, the na tive coherence of ontogeny, or biologi cal development. Indeed, the capacity to evolve and adapt may itself be an achievement of evolution. The studies supporting these conclu sions remain tentative and incomplete. Nevertheless, on the basis of mathe matical models for biological systems that exhibit self-organization,. one can make predictions that are consistent with the observed properties of organ isms. We may have begun to understand evolution as the marriage of selection and self-organization. To understand how self-organization STUART A. KAUFFMAN has been thinking about self-organization in liv ing things since 1965. After studying at Dartmouth College and at the Universi ty of Oxford, he went on to receive his medical degree from the University of California, San Francisco, in 1968. Since then, he has held positions at the Mas sachusetts Institute of Technology,

Molecular Diversity, 1995

Libraries of random-sequence polypeptides have been shown to be valuable sources of novel molecul... more Libraries of random-sequence polypeptides have been shown to be valuable sources of novel molecules possessing a variety of useful biologic-like activities, some of which may hold promise as potential vaccines and therapeutics. Previous random peptide expression systems were limited to low levels of peptide production and often to short sequences. Here we describe a series of libraries designed for increased polypeptide length. Cloned as carboxy-terminal extensions of ubiquitin, the fusions were produced in E. coli at high levels, and were purified to homogeneity. The majority of the extension proteins examined could be cleaved from ubiquitin by treatment with a ubiquitin-fusion hydrolase. The libraries described here are appropriate sources of novel polypeptides with desired binding or catalytic function, as well as tools with which to examine inherent properties of proteins as a whole. Toward the latter goal, we have examined structural properties of random-sequence proteins purified from these libraries. Quite surprisingly, fluorescence emission spectra of intrinsic tryptophan residues in several purified fusion proteins, under native-like and denaturing conditions, often resemble those expected for folded and unfolded states, respectively. The results presented here detail an important expansion in the range of potential uses for random-sequence polypeptide libraries.

Genes, 2011

Biological proteins are known to fold into specific 3D conformations. However, the fundamental qu... more Biological proteins are known to fold into specific 3D conformations. However, the fundamental question has remained: Do they fold because they are biological, and evolution has selected sequences which fold? Or is folding a common trait, widespread throughout sequence space? To address this question arbitrary, unevolved, random-sequence proteins were examined for structural features found in folded, biological proteins. Libraries of long (71 residue), random-sequence polypeptides, with ensemble amino acid composition near the mean for natural globular proteins, were expressed as cleavable fusions with ubiquitin. The structural properties of both the purified pools and individual isolates were then probed using circular dichroism, fluorescence emission, and fluorescence quenching techniques. Despite this necessarily sparse "sampling" of sequence space, structural properties that define globular biological proteins, namely collapsed conformations, secondary structure, and cooperative unfolding, were found to be prevalent among unevolved sequences. Thus, for polypeptides the size of small proteins, natural selection is not necessary to account for the compact and cooperative folded states observed in nature.

Seminars in Cell & Developmental Biology, 2009

Cell lineage commitment and differentiation are governed by a complex gene regulatory network. Di... more Cell lineage commitment and differentiation are governed by a complex gene regulatory network. Disruption of these processes by inappropriate regulatory signals and by mutational rewiring of the network can lead to tumorigenesis. Cancer cells often exhibit immature or embryonic traits and dysregulated developmental genes can act as oncogenes. However, the prevailing paradigm of somatic evolution and multi-step tumorigenesis, while useful in many instances, offers no logically coherent reason for why oncogenesis recapitulates ontogenesis. The formal concept of "cancer attractors", derived from an integrative, complex systems approach to gene regulatory network may provide a natural explanation. Here we present the theory of attractors in gene network dynamics and review the concept of cell types as attractors. We argue that cancer cells are trapped in abnormal attractors and discuss this concept in the light of recent ideas in cancer biology, including cancer genomics and cancer stem cells, as well as the implications for differentiation therapy.