Occupational lung cancer and smoking: a review in the light of current theories of carcinogenesis.

This paper considers modern theories of carcinogenesis as they apply to the induction of lung cancer by tobacco smoking and occupational exposure to carcinogens. Some of the known and postulated factors affecting carcinogenesis are discussed, with particular reference to syncarcinogenesis and thresholds. Factors affecting the intensity of smoking exposure are reviewed, and the generally accepted occupational lung carcinogens are listed. Relative risks for the various carcinogens according to smoking status (where known) are presented. The carcinogens are considered individually, and known or postulated interactions with smoking are discussed. It is concluded that the effects of lung carcinogens can be explained on the basis of current theories that support a rational definition of priorities for the prevention of occupational lung cancer.     

Rules of thumb for judging ecological theories

An impressive fit to historical data suggests to biologists that a given ecological model is highly valid. Models often achieve this fit at the expense of exaggerated complexity that is not justified by empirical evidence. Because overfitted theories complement the traditional assumption that ecology is 'messy', they generally remain unquestioned. Using predation theory as an example, we suggest that a fit-driven appraisal of model value is commonly misdirected; although fit to historical data can be important, the simplicity and generality of a theory--and thus its ecological value--are of comparable importance. In particular, we argue that theories whose complexity greatly exceeds the complexity of the problem that they address should be rejected. We suggest heuristics for distinguishing between valuable ecological theories and their overfitted brethren.     

Autism,theory of mind,and the reactive attitudes

Whether to treat autism as exculpatory in any given circumstance appears to be influenced both by models of autism and by theories of moral responsibility. This article looks at one particular combination of theories: autism as theory of mind challenges and moral responsibility as requiring appropriate experience of the reactive attitudes. In pursuing this particular combination of ideas, we do not intend to endorse them. Our goal is, instead, to explore the implications of this combination of especially prominent ideas about autism and about moral responsibility. These implications can be quite serious and practical for autists and those who interact directly with autists, as well as for broader communities as they attend to the fair, compassionate, and respectful treatment of increasing numbers of autistic adults. We find that these theories point to a limited range of situations in which autists should not be blamed for transgressive actions for which neurotypical individuals should be blamed. We build on what others have written on these issues by bringing in a recent cognitive model of the role theory of mind plays in empathy, by discussing the social implications of the theoretical findings, and by raising questions about the compatibility of reactive attitude theories of moral responsibility with the neurodiversity approach to autism.     

"Not clinically indicated": patients' interests or resource allocation?

The decision that a particular intervention is not clinically indicated may conceal two quite different ethical assumptions. The first assumption is that the intervention is not of overall benefit to this patient. The second is that limited resources should not be used for this patient. These issues are discussed with reference to cardiac surgery in elderly patients with reference to the main theories of allocation: QALYs, needs theories, the sanctity of life theory, the lottery theory, and market forces.     

A theory of precipitation and agglutination reactions in immunological systems

Aggregation phenomena in immunological systems have been profitably treated in the past by applying theories developed to describe polymerization reactions. An interesting result of these theories is the prediction that critical ratios exist for the reactants. These are ratios at which the composition of the system changes abruptly from one characterized primarily by small aggregates to one characterized primarily by large aggregates. In this paper, these ratios are studied as a function of physical and molecular parameters. In particular, the valence of the antibody is allowed to be greater than two and certain types of intramolecular reactions are considered. The effect of antigen and antibody heterogeneity on the results is discussed by developing the theory for a particular heterogeneous system.     

Finite-state models in the alignment of macromolecules

Summary Minimum message length encoding is a technique of inductive inference with theoretical and practical advantages. It allows the posterior odds-ratio of two theories or hypotheses to be calculated. Here it is applied to problems of aligning or relating two strings, in particular two biological macromolecules. We compare the r-theory, that the strings are related, with the null-theory, that they are not related. If they are related, the probabilities of the various alignments can be calculated. This is done for one-, three-, and five-state models of relation or mutation. These correspond to linear and piecewise linear cost functions on runs of insertions and deletions. We describe how to estimate parameters of a model. The validity of a model is itself an hypothesis and can be objectively tested. This is done on real DNA strings and on artificial data. The tests on artificial data indicate limits on what can be inferred in various situations. The tests on real DNA support either the three- or five-state models over the one-state model. Finally, a fast, approximate minimum message length string comparison algorithm is described.Offprint requests to: L. Allison     

Selective scenarios for the emergence of natural language

The recent blossoming of evolutionary linguistics has resulted in a variety of theories that attempt to provide a selective scenario for the evolution of early language. However, their overabundance makes many researchers sceptical of such theorising. Here, we suggest that a more rigorous approach is needed towards their construction although, despite justified scepticism, there is no agreement as to the criteria that should be used to determine the validity of the various competing theories. We attempt to fill this gap by providing criteria upon which the various historical narratives can be judged. Although individually none of these criteria are highly constraining, taken together they could provide a useful evolutionary framework for thinking about the evolution of human language.     

Infanticide as an evolutionarily stable strategy

An evolutionarily stable strategies analysis of infanticide, expressed as two pure strategies, shows that the equilibrial frequency of infanticide depends on only two parameters: the relative advantage of infanticide when others are also infanticidal and the relative advantage of a non-infanticidal strategy if others are non-infanticidal. The possible equilibrial conditions of strictly infanticidal, strictly non-infanticidal, stably polymorphic or history-dependent populations correspond to various earlier models of infanticide. Thus, these earlier models may be subsumed as special cases of the ESS analysis. This permits the comparison of alternative theories of infanticide in specific cases of infanticide in natural populations. In particular, it is argued that if infanticide confers a relative advantage on the perpetrator when other population members are non-infanticidal, this is sufficient to reject a ‘maladaptive’ explanation for infanticide. The potential existence of history-dependent equilibria suggests there will be extreme difficulty with non-experimental methods that attempt to test the adaptiveness of infanticidal behaviour.     

Evolutionary optimality applied to Drosophila experiments: hypothesis of constrained reproductive efficiency

The general purpose of the paper is to test evolutionary optimality theories with experimental data on reproduction, energy consumption, and longevity in a particular Drosophila genotype. We describe the resource allocation in Drosophila females in terms of the oxygen consumption rates devoted to reproduction and to maintenance. The maximum ratio of the component spent on reproduction to the total rate of oxygen consumption, which can be realized by the female reproductive machinery, is called metabolic reproductive efficiency (MRE). We regard MRE as an evolutionary constraint. We demonstrate that MRE may be evaluated for a particular Drosophila phenotype given the fecundity pattern, the age-related pattern of oxygen consumption rate, and the longevity. We use a homeostatic model of aging to simulate a life history of a representative female fly, which describes the control strain in the long-term experiments with the Wayne State Drosophila genotype. We evaluate the theoretically optimal trade-offs in this genotype. Then we apply the Van Noordwijk-de Jong resource acquisition and allocation model, Kirkwood's disposable soma theory. and the Partridge-Barton optimality approach to test if the experimentally observed trade-offs may be regarded as close to the theoretically optimal ones. We demonstrate that the two approaches by Partridge-Barton and Kirkwood allow a positive answer to the question, whereas the Van Noordwijk-de Jong approach may be used to illustrate the optimality. We discuss the prospects of applying the proposed technique to various Drosophila experiments, in particular those including manipulations affecting fecundity.     

Infections génito-urinaires et infécondité masculine: conséquences, diagnostic et traitement

Several experimental and clinical studies have tried to explain the role of genitourinary tract infections on the reproductive function of semen, including recent studies that tried to reveal the negative impact of infections on mobility, in particular, and possibly on the morphological parameters of human spermatozoa. In this review, we attempt to explain the different viewpoints and theories of the various types of genitourinary infections (epididymitis, orchitis, MAGI, prostatitis and urethritis) with a direct impact on normal reproductive values of human semen via the bacteria themselves and via the inflammatory processes. Infections may also be the source of autoantibodies directed against spermatozoa.     

The challenges and scope of theoretical biology

Scientific theories seek to provide simple explanations for significant empirical regularities based on fundamental physical and mechanistic constraints. Biological theories have rarely reached a level of generality and predictive power comparable to physical theories. This discrepancy is explained through a combination of frozen accidents, environmental heterogeneity, and widespread non-linearities observed in adaptive processes. At the same time, model building has proven to be very successful when it comes to explaining and predicting the behavior of particular biological systems. In this respect biology resembles alternative model-rich frameworks, such as economics and engineering. In this paper we explore the prospects for general theories in biology, and suggest that these take inspiration not only from physics, but also from the information sciences. Future theoretical biology is likely to represent a hybrid of parsimonious reasoning and algorithmic or rule-based explanation. An open question is whether these new frameworks will remain transparent to human reason. In this context, we discuss the role of machine learning in the early stages of scientific discovery. We argue that evolutionary history is not only a source of uncertainty, but also provides the basis, through conserved traits, for very general explanations for biological regularities, and the prospect of unified theories of life.     

Biosemantics: An Evolutionary Theory of Thought

Evolutionary theory has an unexpected application in philosophy of mind, where it is used by the so-called biosemantic program—also called the teleosemantic program—to account for the representational capacities of neural states and processes in a way that conforms to an overarching scientific naturalism. Biosemantic theories account for the representational capacities of neural states and processes by appealing in particular to their evolutionary function, as that function is determined by a process of natural selection. As a result, biosemantic theories have distinct advantages over other theories of mental representation—e.g., Fodor’s causal theory. Foremost among the advantages of biosemantic theories is their ability to account for the possibility of mental misrepresentation.     

Apprenticeship in western India

A number of recent attempts to describe what happens in the 'embodied' space between action and the discursive language used to describe that action have been primarily informed by various Western theories of mind. In this article, I present an indigenous theory of what happens among Sunni Muslims in a South Asian context in the gap between linguistic utterances and the actions they purport to represent. The ethnography focuses on learning craft and social skills among apprentices in the shipyards in the Indian state of Gujarat. It is argued that acquiring both kinds of skills is underscored by particular conceptions of the body and the possible transformations of the soul through physical activity.     

Do Organisms Exist?

What is the status of organisms in modern evolutionary biology?I argue that this is a question which centers on the questionof reduction, and towards a complete answer, I pursue issuesthrough three different senses of the term: ontological, methodological,and epistemological. The first sense refers to the ultimatestatus of the entities of the organic world, and in this senseI argue that organisms have no special status. The second senserefers to the question of organization, and I argue that inthe light of modern evolutionary biology organisms do have adistinctive "design-like" organization. The third sense refersto the relationship between theories, in particular to whetherthe theories of the biological sciences can be shown to be logicalconsequences of the theories of the physical sciences. I arguethat such reduction may be possible in principle but difficultin practice. However, from the perspective of the working scientist,this hardly matters. In conclusion, I argue that in some respectsorganisms are not distinctive and in other respects they are.Certainly biologists need not worry for the autonomy of theirsubject.     

The semantic approach to evolutionary theory

Paul Thompson, John Beatty, and Elisabeth Lloyd argue that attempts to resolve certain conceptual issues within evolutionary biology have failed because of a general adherence to the received view of scientific theories. They maintain that such issues can be clarified and resolved when one adopts a semantic approach to theories. In this paper, I argue that such conceptual issues are just as problematic on a semantic approach. Such issues arise from the complexity involved in providing formal accounts of theoretical laws and scientific explanations. That complexity is due to empirical and pragmatic considerations, not one's adherence to a particular formal approach to theories. This analysis raises a broader question. How can any formal account properly represent the complex nature of empirical phenomena?     

Evolutionary mechanisms of senescence

This paper reviews theories of the evolution of senescence. The population genetic basis for the decline with age in sensitivity of fitness to changes in survival and fecundity is discussed. It is shown that this creates a presure of selection that disproportionately favors performance early in life. The extent of this bias is greater when there is a high level of extrinsic mortality; this accounts for much the diversity in life-history patterns among different taxa. The implications of quantitative genetic theory for experimental tests of alternative population genetic models of senescence are discussed. In particular, the negative genetic correlations between traits predicted by the antagonistic pleiotropy model may be obscured by positive correlations that are inevitable in a multivariate system, or by the effects of variation due to deleterious mutations. The status of the genetic evidence relevant to these theories is discussed.     

Inferior olive mirrors joint dynamics to implement an inverse controller

To produce smooth and coordinated motion, our nervous systems need to generate precisely timed muscle activation patterns that, due to axonal conduction delay, must be generated in a predictive and feedforward manner. Kawato proposed that the cerebellum accomplishes this by acting as an inverse controller that modulates descending motor commands to predictively drive the spinal cord such that the musculoskeletal dynamics are canceled out. This and other cerebellar theories do not, however, account for the rich biophysical properties expressed by the olivocerebellar complex’s various cell types, making these theories difficult to verify experimentally. Here we propose that a multizonal microcomplex’s (MZMC) inferior olivary neurons use their subthreshold oscillations to mirror a musculoskeletal joint’s underdamped dynamics, thereby achieving inverse control. We used control theory to map a joint’s inverse model onto an MZMC’s biophysics, and we used biophysical modeling to confirm that inferior olivary neurons can express the dynamics required to mirror biomechanical joints. We then combined both techniques to predict how experimentally injecting current into the inferior olive would affect overall motor output performance. We found that this experimental manipulation unmasked a joint’s natural dynamics, as observed by motor output ringing at the joint’s natural frequency, with amplitude proportional to the amount of current. These results support the proposal that the cerebellum—in particular an MZMC—is an inverse controller; the results also provide a biophysical implementation for this controller and allow one to make an experimentally testable prediction.     

Explanation in morphology

Summary In biology, and particularly in morphology, various types of explanation are found,e.g. causal, teleological, historical, etc.In this article an attempt has been made to analyse the relations between the various explanations to strive for an encompassing explanatory theory.The general structure of the explanatory theories appeared to be very similar, but the terms defining the phenomena and the types of the relations within the theories differ. To obtain a unifying theory it is necessary to develop methods to connect or transform the different elements.An important aspect is that the definition of selected phenomena (terms) depends on the explanation pursued.Lecture presented for the Netherlands Society for Theoretical Biology, December, 1971.     

Can unified theories of biodiversity explain mammalian macroecological patterns?

The idea of a unifying theory of biodiversity linking the diverse array of macroecological patterns into a common theoretical framework is very appealing. We explore this idea to examine currently proposed unified theories of biodiversity (UTBs) and their predictions. Synthesizing the literature on the macroecological patterns of mammals, we critically evaluate the evidence to support these theories. We find general qualitative support for the UTBs' predictions within mammals, but rigorous testing is hampered by the types of data typically collected in studies of mammals. In particular, abundance is rarely estimated for entire mammalian communities or of individual species in multiple locations, reflecting the logistical challenges of studying wild mammal populations. By contrast, there are numerous macroecological patterns (especially allometric scaling relationships) that are extremely well characterized for mammals, but which fall outside the scope of current UTBs. We consider how these theories might be extended to explain mammalian biodiversity patterns more generally. Specifically, we suggest that UTBs need to incorporate the dimensions of geographical space, species' traits and time to reconcile theory with pattern.     

Vibrissae removal and the phenomenon of unexplained sudden death

Two earlier theories on the effect of vibrissae removal in rats were tested. One theory stating that vibrissae removal produces impairment of spatial orientation capacity was confirmed. The other stating that it causes a depressive state of hopelessness and sudden death could not be confirmed. It is concluded that the extrapolation from the particular animal experiment to human psychological processes is not justified.