Contrary to what might be expected given a religious or other motivation, Pierre Duhem's interest in mediaeval science was the result of his surprise encounter with Jordanus de Nemore while working on Les origines de la statique in the late autumn of 1903. Historical assumptions common among physicists at that time may explain this surprise, which occasioned a frantic search for more mediaeval precursors for Renaissance mechanics. It also raised serious historiographical problems that threatened even his methodological views, until they (...) were resolved in his To save the phenomena of 1908. (shrink)

This paper first appeared in Modern Theology, Vol. 6, No. 3, July 1989. Copyright (c) Basil Blackwell Publisher Ltd., Oxford. Reprinted by permission.

Psychiatric disorders present distinct clinical challenges which are partly attributable to their multifactorial aetiology and the absence of laboratory tests that can be used to confirm diagnosis or predict risk. Psychiatric disorders are highly heritable, but also polygenic, with genetic risk conferred by interactions between thousands of variants of small effect that can be summarized in a polygenic risk score. We discuss four areas in which the use of polygenic risk scores in psychiatric research and clinical contexts could have ethical (...) implications. First, there is concern that clinical use of polygenic risk scores may exacerbate existing health inequities. Second, research findings regarding polygenic risk could be misinterpreted in stigmatising or discriminatory ways. Third, there are concerns associated with testing minors as well as eugenics concerns elicited by prenatal polygenic risk testing. Fourth, potential challenges that could arise with the feedback and interpretation of high polygenic risk for a psychiatric disorder would require consideration. While there would be extensive overlap with the challenges of feeding back genetic findings in general, the potential clinical use of polygenic risk scoring warrants discussion in its own right, given the recency of this possibility. To this end, we discuss how lay interpretations of risk and genetic information could intersect. Consideration of these factors would be necessary for ensuring effective and constructive communication and interpretation of polygenic risk information which, in turn, could have implications for the uptake of any therapeutic recommendations. Recent advances in polygenic risk scoring have major implications for its clinical potential, however, care should be taken to ensure that communication of polygenic risk does not feed into problematic assumptions regarding mental disorders or support reductive interpretations. (shrink)

There is little debate regarding the acceptability of providing medical care to restore physical or mental health that has deteriorated below what is considered typical due to disease or disorder (i.e., providing “treatment”—for example, administering psychostimulant medication to sustain attention in the case of attention deficit disorder). When asked whether a healthy individual may undergo the same intervention for the purpose of enhancing their capacities (i.e., “enhancement”—for example, use of a psychostimulant as a “study drug”), people often express greater hesitation. (...) Building on prior research in moral philosophy and cognitive science, in this work, we ask why people draw a moral distinction between treatment and enhancement. In two experiments, we provide evidence that the accessibility of health-related interventions determines their perceived descriptive or statistical normality (Experiment 1), and that gains in descriptive normality for such interventions weaken the moral distinction between treatment and enhancement (Experiment 2). In short, our findings suggest that the tendency to draw a moral distinction between treatment and enhancement is driven, in part, by assumptions about descriptive abnormality; and raise the possibility that normalizing novel biomedical interventions by promoting access could undermine people’s selective opposition toward enhancement, rendering it morally comparable to treatment. (shrink)

While outcomes for children with T-cell acute lymphoblastic leukemia have improved dramatically, survival rates for patients with relapsed/refractory disease remain dismal. Prior studies indicate that glucocorticoid resistance is more common than resistance to other chemotherapies at relapse. In addition, failure to clear peripheral blasts during a prednisone prophase correlates with an elevated risk of relapse in newly diagnosed patients. Here we show that intrinsic GC resistance is present at diagnosis in early thymic precursor T-ALLs as well as in a subset (...) of non-ETP T-ALLs. GC-resistant non-ETP T-ALLs are characterized by strong induction of JAK/STAT signaling in response to interleukin-7 stimulation. Removing IL7 or inhibiting JAK/STAT signaling sensitizes these T-ALLs, and a subset of ETP T-ALLs, to GCs. The combination of the GC dexamethasone and the JAK1/2 inhibitor ruxolitinib altered the balance between pro- and anti-apoptotic factors in samples with IL7-dependent GC resistance, but not in samples with IL7-independent GC resistance. Together, these data suggest that the addition of ruxolitinib or other inhibitors of IL7 receptor/JAK/STAT signaling may enhance the efficacy of GCs in a biologically defined subset of T-ALL.Leukemia advance online publication, 30 May 2017; doi:10.1038/leu.2017.136. (shrink)

Current UK legislation is impacting upon the feasibility and cost-effectiveness of medical record-based research aimed at benefiting the NHS and the public heath. Whereas previous commentators have focused on the Data Protection Act 1998, the Health and Social Care Act 2001 is the key legislation for public health researchers wishing to access medical records without written consent. The Act requires researchers to apply to the Patient Information Advisory Group for permission to access medical records without written permission. We present a (...) case study of the work required to obtain the necessary permissions from PIAG in order to conduct a large scale public health research project. In our experience it took eight months to receive permission to access basic identifying information on individuals registered at general practices, and a decision on whether we could access clinical information in medical records without consent took 18 months. Such delays pose near insurmountable difficulties to grant funded research, and in our case £560 000 of public and charitable money was spent on research staff while a large part of their work was prohibited until the third year of a three year grant. We conclude by arguing that many of the current problems could be avoided by returning PIAG’s responsibilities to research ethics committees, and by allowing “opt-out” consent for many public health research projects. (shrink)