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

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 ..

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.

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

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.

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

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

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.