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 .. (shrink)

Four current accounts of theory reduction are presented, first informally and then formally: (1) an account of direct theory reduction that is based on the contributions of Nagel, Woodger, and Quine, (2) an indirect reduction paradigm due to Kemeny and Oppenheim, (3) an "isomorphic model" schema traceable to Suppes, and (4) a theory of reduction that is based on the work of Popper, Feyerabend, and Kuhn. Reference is made, in an attempt to choose between these schemas, to the explanation of (...) physical optics by Maxwell's electromagnetic theory, and to the revisions of genetics necessitated by partial biochemical reductions of genetics. A more general reduction schema is proposed which: (1) yields as special cases the four reduction paradigms considered above, (2) seems to be in better accord with both the canons of logic and actual scientific practice, and (3) clarifies the problems of meaning variance and ontological reduction. (shrink)

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. (shrink)

We are gratified at the largely positive comments on our essay on the dopamine hypothesis of schizophrenia (DHS) by these two distinguished commentators from the fields of biological psychiatry (Dr. Tamminga) and the philosophy of psychiatry (Dr. Murphy). There is little that they have said with which we disagree. Rather, we want to expand briefly on their commentaries.We found Dr. Tamminga's reactions to be particularly fascinating because she has been an "insider" to the story of the DHS as it has (...) unfolded. She provides substantial insight into the "extra-scientific" reasons for the persistence of the DHS despite its poor empirical record.She validates our impression that the DHS was in its first years of .. (shrink)

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. (shrink)

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. (shrink)

I have not attempted to provide here an analysis of the methodology of molecular biology or molecular genetics which would demonstrate at what specific points a more reductionist aim would make sense as a research strategy. This, I believe, would require a much deeper analysis of scientific growth than philosophy of science has been able to provide thus far. What I have tried to show is that a straightforward reductionist strategy cannot be said to be follwed in important cases of (...) theory development in molecular biology, and that in at least one important case, the Jacob-Monod operon theory, the methodology followed was more biological than chemical. It should be noted in closing, however, that since biological systems are thought by molecular biologists to be nothing but chemical systems, in the long run detailed investigations of such systems will be in full accord with the dictates suggested by the general reduction model. (shrink)

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. (shrink)

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. (shrink)

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]. (shrink)

the structure of medical science with a special focus on the role of generalizations and universals in medicine, and (2) philosophy of medicine's relation with the philosophy of science. I argue that a usually overlooked aspect of Kuhnian paradigms, namely, their characteristic of being "exemplars", is of considerable significance in the biomedical sciences. This significance rests on certain important differences from the physical sciences in the nature of theories in the basic and the clinical medical sciences. I describe those differences (...) and maintain that they are these differentiating features that require the use of more comparative and analogical reasoning in medicine. I suggest that Kitcher's recent introduction of the notion of a ‘practice’ may have similar implications if it is construed to contain more analogical elements than he appears to recognize in his initial formulation. Finally I argue that though Gorovitz and MacIntyre's characterization of medicine as a "science of particulars" bears some similarities with my thesis, I maintain that such a position without careful qualification can lead to ignoring both the nature of generalizations in these sciences and their role as positive analogies tying together a family of overlapping models. Keywords: medical reasoning, biomedical theories/paradigms, science of particulars, philosophy of medicine CiteULike Connotea Del.icio.us What's this? (shrink)

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. (shrink)

This title is part of UC Press's Voices Revived program, which commemorates University of California Press's mission to seek out and cultivate the brightest minds and give them voice, reach, and impact. Drawing on a backlist dating to 1893, Voices Revived makes high-quality, peer-reviewed scholarship accessible once again using print-on-demand technology. This title was originally published in 1985.

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. (shrink)

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. (shrink)

It seems that the above account of explanation-strategy in the area of temperature adaptation underscores many of the points made earlier. First, it discloses the fruitful interaction of classical, evolutionary, and molecular approaches. Secondly, it indicates that biological characterizations are not rival accounts to chemical ones. Thirdly, it stresses the importance of the DNA sequence order in chemical explanations of biological organisms.One feature which this area does not seem to reveal, which genetics does, is the development of a biological (that (...) is, non-chemical) theory which would explain temperature adaptation in nonchemical terms. What this shows is that one should not always expect systematization at the biological level, in the sense of being able to refer many phenomena to a small number of basic principles. The future development of laws and theories in biological terms in this area is, of course, not precluded by the fact that none have yet been discovered. The case does indicate that physical and chemical language and theories are extremely useful in biological investigations, and the physicochemical approach may well be the best approach in this area. In any event, ultimate reduction of the biological to the chemical seems to be a foregone non-controversial conclusion here as elsewhere. (shrink)

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. (shrink)

Caenorhabditis elegans (C. 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. (shrink)

This paper attempts to address the general questionwhether information technologies, as applied in thearea of medicine and health care, have or are likelyto change fundamental concepts regarding disease andhealth. After a short excursion into the domain ofmedical informatics I provide a brief overview of someof the current theories of what a disease is from amore philosophical perspective, i.e. the ``valuefree'' and ``value laden'' view of disease. Next, Iconsider at some length, whether health careinformatics is currently modifying fundamentalconcepts of disease. To (...) this question I will answerlargely in the negative, and I will provide the sketchof some arguments from current research programs inmedical informatics why I think this is the case. Thisargumentation is supported by a detailed account ofhow the disease profile for beriberi heart disease,used in one of the major medical informaticsdiagnostic programs, QMR (and its ancestorINTERNIST-1), was developed, and why at least thisprogram essentially follows received views oftraditional medicine.The one main exception to theconformity of this program to ``received'' views of adisease occurs when the program's designers need tofine-tune a disease definition. This fine-tuning is tocomport with the expert's perspective on the disease,including his or her epistemic values, as well as theprogram's other resources for diagnosing components ofa disease. (shrink)

This paper attempts to address the general question whether information technologies, as applied in the area of medicine and health care, have or are likely to change fundamental concepts regarding disease and health. After a short excursion into the domain of medical informatics I provide a brief overview of some of the current theories of what a disease is from a more philosophical perspective, i.e., the "value free" and "value laden" view of disease. Next, I consider at some length, whether (...) health care informatics is currently modifying fundamental concepts of disease. To this question I will answer largely in the negative. (shrink)

Assessing the normative status of concepts of health and disease involves one in questions regarding the relationship between fact and value. Some have argued that Christopher Boorse's conception of health and disease lacks such a valuational element because it cannot account for types of harms which, while disvalued, do not have evolutionarily dysfunctional consequences. I take Boorse's account and incorporate some Humean-like sociobiological assumptions in order to respond to this challenge. The possession of moral sentiments, I argue, offers an evolutionary (...) advantage (thus falling within Boorse's definition of normal functional abilities). However, this does not amount to emotivism: on the contrary, these sentiments can be the basis of a value system. This value structure introduces the concept of sympathizing with a fellow being's suffering as the basis of a normative dimension to disease. For example, it holds the disvalue of disease to lie in the fact that disease involves suffering and functional limitations.The naturalistic Humean type of account presented here thus jumps the normative-descriptive divide. When Boorse's account is extended to include social sentiments and behaviors, a conception of health emerges which is broader than Boorse's or Kass's, but narrower than the WHO's. (shrink)

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. (shrink)

In this paper I discuss the nature of a broad class of biomedical theories which I have termed "middle-range theories." I define them and relate the nature of biomedical theorizing to other investigations, such as a recent inquiry by the National Academy of Sciences. I also suggest that some of the knowledge representation tools from artificial intelligence may give us a purchase on this type of biological theorizing, and try to show in a rather preliminary and exploratory manner by using (...) the lac operon model of genetic control, what some of those AI applications, such as frames and semantic nets, might look like in this context. Finally, I suggest some difficulties, such as the non-monotonicity of reasoning, which such tools may generate. (shrink)