The virtue of being too early: Paul A. Weiss and 'axonal transport'

The essay introduces how Paul A. Weiss (1898-1989) analyzed his data on neuronal outgrowth and axonal transport, supported by constriction experiments of thousands of living mature nerve fibers. At the University of Chicago his group measured the steady proximo-distal flow of nerve fibers. To visualize the data he used tissue culturing, light microscopy, radioactive tracers, time-lapse motion pictures and electronmicroscopy. The work resulted in the discovery of fasciculation of outgrowing nerves and a computation of the rate of axonal transport, published in a classical article in 1948. He stated that the outgrowth of nerve fibers occurs from nerve centers in their nucleated cell bodies by fasciculation and protein synthesis. However, at that time one suspected the published microphotograph to be an idealized image and, therefore, did not accept the analysis, or the 'new' knowledge. In the mid 1960s the improved technique of autoradiography confirmed in an indirect way Weiss data and analysis of axonal transport. The objective here is to show (1) how Weiss employed the visibility of micrographs and drawings to corroborate his observations and analysis on axonal dynamics, and (2) to offer some tentative suggestions why his colleagues did not accept the 'neuro-images' as an evidence of new knowledge.     

A theory of drug tolerance and dependence I: a conceptual analysis

A mathematical model of drug tolerance and its underlying theory is presented. The model extends a first approach, published previously. The model is essentially more complex than the generally used model of homeostasis, which is demonstrated to fail in describing tolerance development to repeated drug administrations. The model assumes the development of tolerance to a repeatedly administered drug to be the result of a regulated adaptive process. The oral detection and analysis of exogenous substances is proposed to be the primary stimulus for the mechanism of drug tolerance. Anticipation and environmental cues are in the model considered secondary stimuli, becoming primary only in dependence and addiction or when the drug administration bypasses the natural-oral-route, as is the case when drugs are administered intravenously. The model considers adaptation to the effect of a drug and adaptation to the interval between drug taking autonomous tolerance processes. Simulations with the mathematical model demonstrate the model's behavior to be consistent with important characteristics of the development of tolerance to repeatedly administered drugs: the gradual decrease in drug effect when tolerance develops, the high sensitivity to small changes in drug dose, the rebound phenomenon and the large reactions following withdrawal in dependence. The mathematical model verifies the proposed theory and provides a basis for the implementation of mathematical models of specific physiological processes. In addition, it establishes a relation between the drug dose at any moment, and the resulting drug effect and relates the magnitude of the reactions following withdrawal to the rate of tolerance and other parameters involved in the tolerance process. The present paper analyses the concept behind the model. The next paper discusses the mathematical model.     

On the conceptual difficulties in rooting the tree of life

Rooting the 'tree of life' represents a major challenge for evolutionists. Without such a root, many of the first steps in biological evolution cannot be reconstructed. However, the nature of the last common ancestor of all living beings remains elusive, proof of the difficulty in shedding light on such an ancient event. Here, we highlight the practical difficulties and conceptual reasons that hinder the placement of a universal root. We discuss how, when addressing the question of the root of the tree of life, scientists unconsciously risk using the reasoning pattern of ancient skeptics, unfortunately known only to lead to further uncertainty. Hence, we argue that the root of the tree of life will not be established unless radically new approaches are considered. We propose a hypothetical means to overcome several of the conceptual difficulties pointed out, and suggest that a so-called 'transition analysis' of the structural evolution of the cytoplasmic membrane might be helpful, especially if evolutionary steps involving the rooting issue are polarized accounting more for physicochemical knowledge rather than hypothetical and controversial selective advantages.     

Allocation tradeoffs and life histories: a conceptual and graphical framework

Tradeoffs – negative reciprocal causal relationships in net benefits between trait magnitudes – have not always been studied in depth appropriate to their central role in life‐history analysis. Here we focus on allocation tradeoffs, in which acquisition of a limiting resource requires allocation of resource to alternative traits. We identify the components of this allocation process and emphasize the importance of quantifying them. We then propose categorizing allocation tradeoffs into linear, concave and convex relationships based on the way that resource allocation yields trait magnitudes under the tradeoff. Linear relationships are over‐represented in the literature because of typically small data sets over restricted ranges of trait magnitudes, an emphasis on simple correlation analysis, and a failure to remove variation associated with acquisition of the limiting resource in characterizing the tradeoff. (We provide methods for controlling these acquisition effects.) Non‐linear relationships have been documented and are expected under plausible conditions that we summarize. We note ways that shifting environments and biological features yield plasticity of tradeoff graphs. Finally, we illustrate these points using case studies and close with priorities for future work.     

Glynn and the conceptual development of the chemiosmotic theory: A retrospective and prospective view

The origin and evolution of the chemiosmotic theory is described particularly in relation to Peter Mitchell's application of it to model oxidative phosphorylation. Much of the deployment, development and evaluation of the theory occurred at the independent laboratory of the Glynn Research Foundation; the value and future of such an institution is discussed. The role of models mediating between theories and phenomena is analyzed with regard to the growth of knowledge of chemiosmotic systems.     

Brain death and brain life: rethinking the connection

The connection between brain life and brain death is neither as simple nor as defensible as it might at first appear. The problem rests with the two dominant competing definitions of death:...the loss of that which is necessary for the organism to continue to function as a whole;....the loss of that which is essentially significant to the nature of the organism... If death is understood as the loss of that which is necessary for the continued functioning of the organism as whole, then the apparent symmetry breaks down. If...death could be understood as the loss of that which is essentially significant to the nature of the organism....consciousness, then the symmetry would hold. However, that definition of death is indefensible. Therefore...statements about the status of anencephalic infants and early human embryos based upon a connection between brain death and brain life are unfounded.     

On the stochastic theory of compartments: I. A single-compartment system

A stochastic model is developed for a compartment with a single time-dependent input, and generalized to include inputs from several sources. With the number of particles of a given molecular species in the compartment as the random variable, the mean, variance and third central moment of this variable are calculated from its generating function, and compared with previous results. The behavior of the calculated moments is discussed, and the possibility of applying the model to chemical and biological systems is considered.     

Thermodynamics and the conceptual structure of evolutionary theory

Thermodynamics and evolutionary theory have spent most of their shared history in adversarial relationship to one another. The point of this paper is to consider some qualitative ways in which thermodynamics can enrich both the theory and epistemology of evolution. The "autonomy of biology" posture in evolutionary theory hangs on the supposed uniqueness of why-questions in biology. With this posture, and with the general obstruction of constructive dialogue between evolution and the physical sciences it fosters, come the perennial accusations that Darwinism deals in adaptational teleology but not mechanisms. Thermodynamics provides for a two-tiered hierarchy of causation in nature in which the why-question is rendered not only legitimate materialistically, but essential to understanding the evolutionary process in its totality--from the emergence of life to the branching of lineages in speciation.     

A clue to the origin of life: begin from making tools

The small molecules already existing on the earth can be assembled to biological macromolecules in the presence of the suitable tool. A workman must sharpen his tools if he is to do his work well. The tool must be specific, delicate and automatic. Obviously, it is enzyme. Therefore, to explore the origin of life we must understand the origin of the manufacturing tool of biological macromolecules—the origin of enzymes. We can understand more about the origin and evolution procedures of enzymes from the NO₂. NO₂ can easily form the dimmer, N₂O₄. Four N₂O₄ molecules can coordinate with a suitable metal ion and form a plane super molecule with four N₂O₄ molecules. This supramolecule provides the basis for the appearance of enzymes: (1) It is the template for producing enzymes. (2) It provides the active centers for enzymes. (3) It provides for the enzymes with specific function of chiral selection. This supramolecule reacts with formaldehyde and porphyrin compound is gradually formed. Once suitable function groups are substituted on the porphyrin ring, enzymes are formed. The primitive environment of earth can easily produce NO₂ and CH₂O. Therefore, this might be one clue to the origin of life.

R A Fisher,design theory,and the Indian connection

Design Theory, a branch of mathematics, was born out of the experimental statistics research of the population geneticist R A Fisher and of Indian mathematical statisticians in the 1930s. The field combines elements of combinatorics, finite projective geometries, Latin squares, and a variety of further mathematical structures, brought together in surprising ways. This essay will present these structures and ideas as well as how the field came together, in itself an interesting story.     

Collective decision‐making and fission–fusion dynamics: a conceptual framework

Sociality exists in an extraordinary range of ecological settings. For individuals to accrue the benefits associated with social interactions, they are required to maintain a degree of spatial and temporal coordination in their activities, and make collective decisions. Such coordination and decision‐making has been the focus of much recent research. However, efforts largely have been directed toward understanding patterns of collective behaviour in relatively stable and cohesive groups. Less well understood is how fission–fusion dynamics mediate the process and outcome of collective decisions making. Here, we aim to apply established concepts and knowledge to highlight the implications of fission–fusion dynamics for collective decisions, presenting a conceptual framework based on the outcome of a small‐group discussion INCORE meeting (funded by the European Community's Sixth Framework Programme). First, we discuss how the degree of uncertainty in the environment shapes social flexibility and therefore the types of decisions individuals make in different social settings. Second, we propose that the quality of social relationships and the energetic needs of each individual influence fission decisions. Third, we explore how these factors affect the probability of individuals to fuse. Fourth, we discuss how group size and fission–fusion dynamics may affect communication processes between individuals at a local or global scale to reach a consensus or to fission. Finally, we offer a number of suggestions for future research, capturing emerging ideas and concepts on the interaction between collective decisions and fission–fusion dynamics.     

A general theory of life table construction and a precise abridged life table method

"In this paper we lay the foundation of life table construction by unifying the existing life table methods. We also present a new method of constructing current (period) abridged life tables.... The development includes (1) a careful formulation and computation of age-specific death rates, (2) derivation of a new set of formulas for computing the survivorship function from the observed age-specific death rates and populations, (3) estimation of the main life table functions by spline interpolation, integration and differentiation, and (4) use of a quadratic and a Gompertz function to close the life table.... The method is illustrated with construction of abridged life tables using Canadian data."     

On the theory of the cardiovascular system

Most theoretical studies of the circulation have focussed on the transmission line properties of arteries. Only a small number of papers have dealt with the circulation as a closed (lumped) system with two pumps connected by the lesser and greater circulation (Beneken, inCirculatory Analog Computers, No. Holland Publ. Co., Amsterdam, 1963; Defares,et al., inCirculatory Analog Computers, No. Holland Publ. Co., Amsterdam, 1963; Grodins,Quart. Rev. of Biology,34, 93, 1959; Guyton,Cardiac Output and its Regulation, Saunders Publ. Co., New York, 1963). F. W. Cope's recent studies in this journal (Bull. Math. Biophysics,22, 19, 1960;23, 337, 1961;24, 137, 1962) deal with essentially the same questions, although here the circuit is not “closed”. We have attempted to extend the analysis of the areflex (closed) circulation. The complete study is reported elsewhere (Defares,et al., Acta Physiol, et Parmac. Neerl., 1963).     

On limiting nutrient patchiness and phytoplankton growth: a conceptual approach

A theoretical framework is developed to explore the effectsof limiting nutrient patchiness on phytoplankton growth. Growthrate is represented as a function of the average ambient substrateconcentration in the medium, the degree of patchiness and thepatch duration. Phytoplankton growth, in relation to the externalsubstrate concentration, is mediated by the cell quota for thelimiting nutrient. Two general conclusions can be drawn from this study. Firstthe degree of patchiness in the environment can affect individualgrowth rates and thus alter community structure even thoughthere is no change in the average ambient nutrient concentration.Second, for patch-adapted populations, the apparent K_s for growthcan be lowered significantly by making the distribution of thelimiting nutrient patchy with respect to time. The insightswhich this model provides into future experimental methodologiesare also discussed. ¹ Address for reprints² also Dept. Botany³ also Institute of Applied Mathematics