Charles J. Lumsden

A one-hit model of cell death in inherited neuronal degenerations

In genetic disorders associated with premature neuronal death, symptoms may not appear for years or decades. This delay in clinical onset is often assumed to reflect the occurrence of age-dependent cumulative damage. For example, it has been suggested that oxidative stress disrupts metabolism in neurological degenerative disorders by the cumulative damage of essential macromolecules. A prediction of the cumulative damage hypothesis is that the probability of cell death will increase over time. Here we show in contrast that the kinetics of neuronal death in 12 models of photoreceptor degeneration, hippocampal neurons undergoing excitotoxic cell death, a mouse model of cerebellar degeneration and Parkinsons and Huntingtons diseases are all exponential and better explained by mathematical models in which the risk of cell death remains constant or decreases exponentially with age. These kinetics argue against the cumulative damage hypothesis; instead, the time of death of any neuron is random. Our findings are most simply accommodated by a ‘one-hit’ biochemical model in which mutation imposes a mutant steady state on the neuron and a single event randomly initiates cell death. This model appears to be common to many forms of neurodegeneration and has implications for therapeutic strategies.

Genes, mind, and culture : the coevolutionary process

# The Next Synthesis: 25 Years of Genes, Mind, and Culture # The Primary Epigenetic Rules # The Secondary Epigenetic Rules # Gene-Culture Translation # The Gene-Culture Adaptive Landscape # The Coevolutionary Circuit # The Biogeography of the Mind # Gene-Culture Coevolution and Social Theory

The creative mind: Toward an evolutionary theory of discovery and innovation

Abstract The creative mind remains largely uncharted despite the efforts of investigators from many fields. Discussions arising from the perspective of evolutionary biology have helped somewhat to clarify the problems surrounding human creative activity. However, even the most advanced evolutionary treatments are unable to provide thorough explanations of creative activity or to deal productively with its effects on behavior and society. Moreover, it appears that such explanations will not be forthcoming within the current evolutionary paradigm. Our purpose in this report is to present a potentially new evolutionary approach to human creativity. We begin by introducing the concept of a system in which the components of individual cognition, including intelligence, learning, memory, personality and motivation interact with features of the sociocultural environment such as social stratification, educational policies and modes of communication to influence the creative process, discovery and innovation. Implicit in this concept is the assertion that a productive characterization of the creative process cannot be stated solely by reference to a single level of organization. Empirical evidence corroborating this assertion is examined. Our system concept is then integrated with current theories of biocultural dynamics, leading to the hypothesis that creative activity is an evolved strategy in which rules of cognitive development act through the joint inheritance of genetic and cultural information. Data from cognitive science, social anthropology and behavior genetics, testing the hypothesis of genetic involvement in creative development, are presented and discussed. Building on previous investigations, we suggest that creative potential in particular problem domains relates to the organization of semantic networks through the forging of links among previously dissociated elements. Formalization of this linking thesis in turn generates several quantitative predictions about domain specificity, the relationship between creative potential and age, environmental complexity, and various aspects of the sociocultural environment. A central problem in our theory of discovery and innovation is how creative activity is instantiated in the functional architecture of the brain. We develop a model in which creative activity is related to the patterns of activation among collections of neurons that are innately predisposed to respond to particular patterns of electrochemical excitation. In this formulation, the creative process — manifested at the cognitive level by the establishment of new linkages among nodes in the existing knowledge structure — arises as a consequence of the elaboration of a novel sequence of group selection events. The model is found to generate a number of testable predictions concerning, for example, the relationship between creative potential and temporal environmental heterogeneity. Moreover, it appears to offer an explanation for such individual characteristics as the domain-specificity of creative potential. A particularly intriguing prediction arising from the model is that above some basal level of sensorimotor activity, creativity may well be independent of the primary information transduction capacities of the organism. The concluding sections of the report develop two related themes. First, we suggest that current mathematical models of cultural change and gene-culture coevolution have difficulty dealing with intervals of history containing successive innovations. In the existing formulations, creative potentials, innovation rates, etc. are likely to enter as extrinsic parameters or driving forces similar to mutation rates, rather than as causal outcomes of developmental and behavioral events within the system. This limits their usefulness in applications to culturally transmitted novelty. However, it is possible at least to begin construction of improved formal frameworks, the so-called superspace theories, which can better accomodate unforeseen discoveries and their consequences. This step makes possible improved macroevolutionary treatments of social change. Second, we consider in some detail the possibility that the formidable problems posed by creative diversity can be surmounted or at least eased. Our analysis suggests that all types of creative products may well be accommodated within a single multidimensional space of basic properties, with individual elements differing according to the particulars of their associated symbol systems and sustaining cognitive processes. Some tentative taxonomic principles are developed and applied. Preliminary evaluation of these classifications suggests that human creativity will be further clarified by the continued synthesis of evolutionary biology with the cognitive sciences.

Incest Avoidance as a Function of Environment and Heredity [and Comments and Reply]

Although it has repeatedly been demonstrated that behavior is best understood as a function of the interrelatedness of nature and nurture, many social scientists persist in posing these determinants adversatively and then contend that genes and biology are, at best, minor determinants of behavior. Analysis in incest avoidance illustrates the inadequacy of efforts to reduce to irrelevance genetic determinants. Man and many other species exhibit strong tendencies to avoid incest. Conspecifics who are intimately associated during the infancy and childhood of one or both do not find each other sexually attractive if alternative mates are available. Migration shortly after puberty, usually by the male, is characteristics of social primates. Incest vere seldom occurs, and when it does the copulatory act differs markedly from normal mating. Incest within intact human families is rare. Inbreeding with other close relatives is inhibited by human awareness of inbreeding depression, not by any apparent genetic predisposition. Societies which discourage close inbreeding should be more viable than those which encourage it. Their behaviors can only be explained as a result of environment interacting with heredity. Concern is expressed about the damage done to the social sciences by denial of relevance to biological and genetic factors.

Ritualized combat and intercolony communication in ants

Abstract Colonies of the honey ant Myrmecocystus mimicus engage each other in elaborate display tournaments. Hundreds of ants are often involved, but almost no physical fights occur. Instead, opponents confront one another in highly aggressive displays, during which they walk on stilt legs while raising their abdomens and heads. The tournaments serve as temporary spatial borders within which food gathering occurs. In this study we develop the hypothesis that tournaments are a mechanism of intercolony communication, which opposing colonies use to gauge each others strength. Models are proposed for the behaviorial procedures that seem most likely to underly this capacity. For the first time it is possible to ascertain and compare the properties of such models in relation to a body of test data. It appears probable to us that intercolony communication in this species of ant may depend upon a novel capacity for integrative information harvesting by individual workers.

Précis of Genes, Mind, and Culture

Despite its importance, the linkage between genetic and cultural evolution has until now been little explored. An understanding of this linkage is needed to extend evolutionary theory so that it can deal for the first time with the phenomena of mind and human social history. We characterize the process of gene-culture coevolution, in which culture is shaped by biological imperatives while biological traits are simultaneously altered by genetic evolution in response to cultural history. A case is made from both theory and evidence that genetic and cultural evolution are inseverable, and that the human mind has tended to evolve so as to bias individuals toward certain patterns of cognition and choice rather than others. With the aid of mathematical models we trace the coevolutionary circuit: The genes prescribe structure in developmental pathways that lay down endocrine and neural systems, imposing regularities in the development of cognition and behavior; these regularities (loosely labeled “epigenetic rules”) translate upward into holistic patterns of culture, which can be predicted in the form of probability density distributions (ethnographic curves); natural selection acts within human history to favor certain epigenetic rules over others; and the selection alters the frequencies of the underlying genes. The effects of genetic and cultural changes reverberate throughout the circuit and are consequently tested with the passage of each life cycle. In addition to modeling gene-culture coevolution, we apply methods from island biogeography and information theory to examine the cultural capacity of the genes, the factors determining the magnitude of cultural diversity, and the possible reasons for the uniqueness of the human achievement.

Cultural evolution and the devolution of tabula rasa

The available evidence from human cognitive and developmental psychology indicates that mental development is the environmentally modulated activity of innate mechanisms, or epigenetic rules, which lay down neural and endocrine tissues, imposing regularities on the growth of mental processes and behavior. Although evolutionary models that deal with single epigenetic rules have previously been reported, still unaddressed is the problem of organization and complexity in assemblages of epigenetic rules, which are crucial for normal mental development. In this report, models are formulated in order to predict for simple first cases the evolutionarily stable size of systems of functionally related epigenetic rules. The coevolutionary responses of such systems to major types of culture change are worked out. Trends toward increasing sustenance, increased social stratification, and increased cultural complexity have in social theories often been intuited as progression away from an innate, primitive, human nature. The results of the present study suggest that such intuitions may not be valid. More, rather than fewer, innate biological constraints are found to assemble minds adapted to each of these more advanced types of social system.

Portable mood mapping: the validity and reliability of analog scale displays for mood assessment via hand-held computer.

The long-term natural time course of mood change remains poorly understood, and improved methods that assay multiple mood symptoms quickly and reliably are crucial to further progress. This study describes the reliability and validity of the new visual analog scale (VAS) display method for a recently developed 19-item VAS-based mood questionnaire, the VMQ, administered via hand-held computer (HHC). The effect of the smaller HHC screen size on accuracy and precision of VAS completion was investigated in 28 subjects using 4- and 10-cm paper-based VASs to indicate six specified dates within the year. The influence of digital vs. paper medium was then tested in 39 subjects who completed the same task, using 10-cm paper and 4-cm HHC-based VASs. Test-retest reliability was evaluated in 29 subjects who completed the questionnaire on a HHC twice, 10 min apart. Since the HHC presents VMQ scales with text anchor orientation set randomly, we also considered whether subjects might inadvertently transpose responses on the HHC. We found that reducing VAS size produced no significant loss of response precision or accuracy in subject response. Moreover, there was no significant loss of accuracy or precision between 10-cm paper and 4-cm HHC-based versions of the VAS. HHC-based items also demonstrated excellent test-retest reliability, with excellent values of Cronbachs alpha. The transposition error rate was negligible (0.27%). Our study provides initial evidence that the HHC-based VAS display used in the VMQ is a reliable and valid tool for comprehensive collection of analog mood scale data.

Heterogeneous cellular environments modulate one-hit neuronal death kinetics

We recently demonstrated that cell loss kinetics in diverse forms of neurodegeneration (ND) suggests a universal death switch mechanism in which each cell is at a constant risk to initiate apoptosis. We proposed that mutant and injured neurons exist in a viable state typified by an increased risk of initiating death processes [Clarke, Collins, Leavitt, Andrews, Hayden, Lumsden, McInnes, A one-hit model of cell death in inherited neuronal degenerations, Nature 406 (2000) 195-199]. To date, however, measurements of cell death risk have been available only as averages across the affected cell population. Here we develop and apply a method of death kinetic analysis in which the risk factors vary across the neuronal population, as for example due to regional heterogeneities in the cellular microenvironment. We find that most cases of ND for which cell loss data has been obtained are better explained by death risks that vary from cell to cell, compared to death risk that is constant across the neuronal population. Strikingly, a common form of the frequency distribution defining the death risk heterogeneity is shared across most of these cases. This first characterization of the kinetic heterogeneity in one-hit neuronal death, therefore, suggests that the wide variety of ND now known may share mechanisms through which regional differences in the cellular microenvironment modulate the kinetics of cell loss.

Behavioral evolution and biocultural games: oblique and horizontal cultural transmission

We consider an evolutionary game model in which strategies are culturally transmitted among individuals rather than inherited biologically. In addition to vertical transmission (from parents to offspring), we investigate the effects of oblique (from members of the parental generation to offspring) and horizontal (among age peers) transmission on game dynamics. Our study yields two important results. Firstly, biocultural games show a greater diversity of dynamical behaviors than their purely biological counterparts, including multiple fully polymorphic equilibria. Secondly, biocultural games on average show greater equilibrium strategy diversity. These results suggest that cultural transmission in the presence of natural selection may be an important mechanism maintaining behavioral diversity in natural populations.