Kenneth Schaffner

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

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

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.

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 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.

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.

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.

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

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.

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.

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.