Kenneth Schaffner

The study of mental illness by the methods of molecular genetics is still in its infancy, but the use of genetic markers in psychiatry may potentially lead to a Virchowian revolution in the conception of mental illness. Genetic markers may define novel clusters of patients having diverse clinical presentations but sharing a common genetic and mechanistic basis. Such clusters may differ radically from the conventional classification schemes of psychiatric illness. However, the reduction of even relatively simple Mendelian phenomena to molecular genetics has been shown to be a surprisingly complex and problematic enterprise. Mental illnesses exist at many levels of including social, environmental, and developmental interactions. Reductionistic shifts in the classification of such a disease entity will have to address the interlevel dynamics that take place within the structure of theories of mental illness. The question of how molecular analysis of psychiatric disease will impact on the structure of existing theories and classification systems is the central topic of this paper

Two problems in the paper by EGR are considered. One is the lack of any direct confirmatory evidence for the elegant rational reconstruction. The second is a significant gap in the historical account, just at the critical point in Einstein's discovery process -- namely, the reanalysis of simultaneity. In addition, the EGR account appears in danger of being overly focused on the electrodynamical aspect of special relativity to the exclusion of optical null experiments, and in particular to the exclusion of the role of the 1887 Michelson-Morely interferometer experiment. The author disagrees with Miller on the Kantian aspects of Poincare, and on the role of Anschauungen, preferring to sketch instead a more important role for a Mach-like analysis of fundamental scientific concepts. It is argued that Miller has misconstrued the difference between an axiomatic theory and a "theory of principle" in Einstein's approach. Finally, some suggestions are made as to how the gap in our analysis of Einstein's revolution in simultaneity might be reexamined.

Behaving presents an overview of the recent history and methodology of behavioral genetics and psychiatric genetics, informed by a philosophical perspective. Kenneth F. Schaffner addresses a wide range of issues, including genetic reductionism and determinism, "free will," and quantitative and molecular genetics. The latter covers newer genome-wide association studies that have produced a paradigm shift in the subject, and generated the problem of "missing heritability." Schaffner also presents cases involving pro and con arguments for genetic testing for IQ and for Attention Deficit Hyperactivity Disorder. Schaffner examines the nature-nurture controversy and Developmental Systems Theory using C. elegans or "worm" studies as a test case, concluding that genes are special and provide powerful tools, including "deep homology," for investigating behavior. He offers a novel account of biological knowledge emphasizing the importance of models, mechanisms, pathways, and networks, which clarifies how partial reductions provide explanations of traits and disorders. The book also includes examinations of personality genetics and of schizophrenia and its etiology, alongside interviews with prominent researchers in the area, and discusses debates about psychosis that led to changes in the DSM-5 in 2013.Schaffner concludes by discussing additional philosophical implications of the genetic analyses in the book, some major worries about "free will," and arguments pro and con about why genes and DNA are so special. Though genes are special, newer perspectives presented in this book will be needed for progress in behavioral genetics- perspectives that situate genes in complex multilevel prototypic pathways and networks. With a mix of optimism and pessimism about the state of the field and the subject, Schaffner's book will be of interest to scholars in the history and philosophy of science, medicine, and psychiatry.

This essay selectively reviews, from an historical and philosophical perspective, the dopamine (DA) hypothesis of schizophrenia (DHS; Table 1 lists the abbreviations used in this essay). Our goal is not to adjudicate the validity of the theory—although we arrive at a generally skeptical conclusion—but to focus on the process whereby the DHS has evolved over time and been evaluated. Since its inception, the DHS has been the most prominent etiologic theory in psychiatry and is still referred to widely in current textbooks (e.g., Buchanan and Carpenter, Jr. 2005, 1336; Cohen 2003, 225; Gazzaniga 2004, 1257;Kandel et al. 2000, 1200). Understanding its origins and evolution should help to clarify the nature of modern ..

In the present article I have surveyed several approaches to modeling the clinical diagnostic process. I have argued that at this point of the field's development, logics which simulate the reasoning patterns and knowledge base of expert clinicians represent research programs that are most likely to succeed. No logic of diagnosis has yet attained the status of being definitive; in spite of striking progress much more research and testing is required. On the basis of various existing logics, I have attempted to articulate a number of desiderata which an ideal diagnostic logic should satisfy. In spite of these criticisms, I would maintain that programs such as MYCIN and INTERNIST have already matured to the point where they are useful both in consultations and in teaching diagnostic reasoning

The traditional role which correspondence rules, coordinating definitions, or semantical rules, have in a logical analysis of a scientific theory is questioned by providing an alternative analysis. The alternative account suggests that scientific theories are "meaningful" prior to the establishment of correspondence rules, and that correspondence rules are introduced to permit explanation and testing in the "observational" sector. The role of models is briefly assessed in connection with this prior or "antecedent theoretical meaning," and a causal sequence analysis of a class of correspondence rules is presented which makes explicit the interdependence of scientific theories

This two-part article examines the competition between the clonal selection theory and the instructive theory of the immune response from 1957–1967. In Part I the concept of a temporally extended theory is introduced, which requires attention to the hitherto largely ignored issue of theory individuation. Factors which influence the acceptability of such an extended theory at different temporal points are also embedded in a Bayesian framework, which is shown to provide a rational account of belief change in science. In Part II these factors, as elaborated in the Bayesian framework, are applied to the case of the success of the clonal selection theory and the failure of the instructive theory.

Early last year, the GenEthics Consortium (GEC) of the Washington Metropolitan Area convened at George Washington University to consider a complex case about genetic testing for Alzheimer disease (AD). The GEC consists of scientists, bioethicists, lawyers, genetic counselors, and consumers from a variety of institutions and affiliations. Four of the 8 co-authors of this paper delivered presentations on the case. Supplemented by additional ethical and legal observations, these presentations form the basis for the following discussion

In the above pages I have sketched a history of the genesis and comparative evaluation of the repressor model of genetic regulation of enzyme induction. I have not attempted in this article to carry out an analysis of the more scientifically interesting fully developed Jacob-Monod operon theory of genetic regulations but such an analysis of the operon theory would not, I believe, involve any additional logical or epistemological features than have been discussed above. I have argued that the above account of the development of a theory of enzyme induction involved inferential moves and well-characterized desiderata, of both empirical and non-empirical character, in the genesis and evaluation of new hypotheses and theories. I have also contended that the reasoning displayed in the genesis of a theory is in a large measure identical to that utilized in evaluating a theory. Both of these conclusions are at variance with the views of philosophers such as H. Reichenbach, Sir Karl Popper, and C.G. Hempel who have argued that the genesis of new hypotheses is primarily an irrational affair and that only the context of justification is susceptible of rational reconstruction. In the alternative view presented here, scientific discovery and scientific justification represent the application in contexts, which are primarily telically distinguishable, of a fundamentally unitary logic of scientific inquiry

The contemporary epistemic status of mental health disciplines does not allow the cross validation of mental disorders among various genetic markers, biochemical pathway or mechanisms, and clinical assessments in neuroscience explanations. We attempt to provide a meta-empirical analysis of the contemporary status of the cross-disciplinary issues existing between neuro-biology and psychopathology. Our case studies take as an established medical mode an example cross validation between biological sciences and clinical cardiology in the case of myocardial infarction. This is then contrasted with the incoherence between neuroscience and psychiatry in the case of bipolar disorders. We examine some methodological problems arising from the neuro-imaging studies, specifically the experimental paradigm introduced by the team of Wayne Drevets. Several theoretical objections are raised: temporal discordance, state independence, and queries about the reliability and specificity, and failure of convergent validity of the inter-disciplinary attempt. Both modern neuroscience and clinical psychology taken as separate fields have failed to reveal the explanatory mechanisms underlying mental disorders. The data acquired inside the mono-disciplinary matrices of neurobiology and psychopathology are deeply insufficient concerning their validity, reliability, and utility. Further, there haven’t been developed any effective trans-disciplinary connections between them. It raises the requirement for development of explanatory significant multi-disciplinary “meta-language” in psychiatry (Berrios, 2006, 2008). We attempt to provide a novel conceptual model for an integrative dialogue between psychiatry and neuroscience that actually includes criteria for cross-validation of the common used psychiatric categories and the different assessment methods. The major goal of our proactive program is the foundation of complementary “bridging” connections of neuroscience and psychopathology which may stabilize the cognitive meta-structure of the mental health knowledge. This entails bringing into synergy the disparate discourses of clinical psychology and neuroscience. One possible model accomplishment of this goal would be the synergistic (or at least compatible) integration of the knowledge under trans-disciplinary convergent cross-validation of the commonly used methods and notions.

The question of the influence of genes on behavior raises difficult philosophical and social issues. In this paper I delineate what I call the Developmentalist Challenge (DC) to assertions of genetic influence on behavior, and then examine the DC through an indepth analysis of the behavioral genetics of the nematode, C. elegans, with some briefer references to work on Drosophila. I argue that eight "rules" relating genes and behavior through environmentally-influenced and tangled neural nets capture the results of developmental and behavioral studies on the nematode. Some elements of the DC are found to be sound and others are criticized. The essay concludes by examining the relations of this study to Kitcher's antireductionist arguments and Bechtel and Richardson's decomposition and localization heuristics. Some implications for human behavioral genetics are also briefly considered

This article considers claims that biology should seek general theories similar to those found in physics but argues for an alternative framework for biological theories as collections of prototypical interlevel models that can be extrapolated by analogy to different organisms. This position is exemplified in the development of the Hodgkin‐Huxley giant squid model for action potentials, which uses equations in specialized ways. This model is viewed as an “emergent unifier.” Such unifiers, which require various simplifications, involve the types of heuristics discussed in Wimsatt’s writings on reduction, but with a twist. Here, the heuristics are used to generate emergent rather than reductive explanations. †To contact the author, please write to: Department of History and Philosophy of Science, University of Pittsburgh, 1017 Cathedral of Learning, Pittsburgh, PA 15260; e‐mail: [email protected].

In this paper, I propose two theses, and then examine what the consequences of those theses are for discussions of reduction and emergence. The first thesis is that what have traditionally been seen as robust, reductions of one theory or one branch of science by another more fundamental one are a largely a myth. Although there are such reductions in the physical sciences, they are quite rare, and depend on special requirements. In the biological sciences, these prima facie sweeping reductions fade away, like the body of the famous Cheshire cat, leaving only a smile.... The second thesis is that the "smiles" are fragmentary patchy explanations, and though patchy and fragmentary, they are very important, potentially Nobel-prize winning advances. To get the best grasp of these "smiles," I want to argue that, we need to return to the roots of discussions and analyses of scientific explanation more generally, and not focus mainly on reduction models, though three conditions based on earlier reduction models are retained in the present analysis. I briefly review the scientific explanation literature as it relates to reduction, and then offer my account of explanation. The account of scientific explanation I present is one I have discussed before, but in this paper I try to simplify it, and characterize it as involving field elements and a preferred causal model system abbreviated as FE and PCMS. In an important sense, this FE and PCMS analysis locates an "explanation" in a typical scientific research article. This FE and PCMS account is illustrated using a recent set of neurogenetic papers on two kinds of worm foraging behaviors: solitary and social feeding. One of the preferred model systems from a 2002 Nature article in this set is used to exemplify the FE and PCMS analysis, which is shown to have both reductive and nonreductive aspects. The paper closes with a brief discussion of how this FE and PCMS approach differs from and is congruent with Bickle's "ruthless reductionism" and the recently revived mechanistic philosophy of science of Machamer, Darden, and Craver.

Caenorhabditis elegans is a tiny worm that has become the focus of a large number of worldwide research projects examining its genetics, development, neuroscience, and behavior. Recently several groups of investigators have begun to tie together the behavior of the organism and the underlying genes, neural circuits, and molecular processes implemented in those circuits. Behavior is quintessentially organismal—it is the organism as a whole that moves and mates—but the explanations are devised at the molecular and neurocircuit levels, and tested in populations using protocols that span many levels of aggregation. Following a brief review of the main relevant features of C. elegans, I describe some of these circuits, and then discuss two contrasting approaches in behavioral genetics and neural network analysis of the worm. Finally, I outline the rudiments of a “field and focus” explanation model using the two contrasting approaches.

In this rejoinder to the three preceding comments, I provide some additional philosophical warrant for the biomedical sciences' focus on model organisms. I then relate the inquiries on model systems to the concept of 'deep homology', and indicate that the issues that appear to divide my commentators and myself are in part empirical ones. I cite recent work on model organisms, and especially C. elegans that supports my views. Finally, I briefly readdress some of the issues raised by Developmental Systems Theory

This article examines how a molecular "solution" to an important biological problem-how is antibody diversity generated? was obtained in the 1970s. After the primarily biological clonal selection theory (CST) was accepted by 1967, immunologists developed several different contrasting theories to complete the SCST. To choose among these theories, immunology had to turn to the new molecular biology, first to nucleic acid hybridization and then to recombinant DNA technology. The research programs of Tonegawa and Leder that led to the "solution" are discussed, and some of their strategies and heuristics are broadly characterized: (1) to what extent does the new recombinant DNA technology provide what the scientists claim is "direct evidence," what does that term mean, and what are the implications of that claim for biological "realism," and (2) is this episode one of reduction, partial reduction, or explanatory extension, and what do these terms mean in the context of a successful molecular "solution" to a biological problem.

This paper examines the nature of theory structure in biology and considers the implications of those theoretical structures for theory reduction. An account of biological theories as interlevel prototypes embodying causal sequences, and related to each other by strong analogies, is presented, and examples from the neurosciences are provided to illustrate these middle-range theories. I then go on to discuss several modifications of Nagel''s classical model of theory reduction, and indicate at what stages in the development of reductions these models might best apply. Finally I consider several implications of these analyses of theory structure and reduction for disciplinary integration in biology.