The undue influence of genetic information on senior medical students' treatment decisions.

BACKGROUND: Knowledge of the genetic basis of health conditions can influence how the public perceives their own and others' health. When there are known genetic associations for such conditions, genetic essentialist biases facilitate deterministic thinking and an over-emphasis of genetic causality. This study investigates the role that genetic essentialist biases play in medical decision-making. METHODS: Senior postgraduate medical students (N = 102) read a scenario in which a patient presents with gastroenterological symptoms. Half of the students were told that the patient tested positive for HLADQ2 - a gene implicated in, but not deterministic of, coeliac disease. The other half received no genetic information. Students were assessed on their recommendations for investigation and management using a multiple-choice questionnaire. Twenty-two of these students participated in a qualitative follow-up which used focus groups and semi-structured interviews to explore the reasoning behind students' responses. RESULTS: Management recommendations differed between the two groups, with those receiving genetic information more likely to recommend a gluten free diet. Recommendations for further investigation did not differ significantly between groups. Interviews suggested that these findings arose despite the students' good understanding of the common non-deterministic nature of genes, such as HLADQ2. CONCLUSION: Differences in management recommendations suggest that the inclusion of genetic information unduly biased students towards a premature diagnosis of a serious health condition, coeliac disease. Follow-up interviews introduced the possibility that observed manipulation-based differences may have been based on anticipated expectations of examiners, rather than perceived future clinical practice. Based on the present results it is unclear whether intentional exam-taking strategies fully account for medical students' decisions, or if they contribute in addition to the activation of genetic essentialist biases. Further research in clinical settings may ascertain whether genetic essentialist biases would truly influence medical student and doctors within their clinical practice environment.

Causal Reasoning About Human Behavior Genetics: Synthesis and Future Directions.

When explaining the causes of human behavior, genes are often given a special status. They are thought to relate to an intrinsic human 'essence', and essentialist biases have been shown to skew the way in which causation is assessed. Causal reasoning in general is subject to other pre-existing biases, including beliefs about normativity and morality. In this synthesis we show how factors which influence causal reasoning can be mapped to a framework of genetic essentialism, which reveals both the shared and unique factors underpinning biases in causal reasoning and genetic essentialism. This comparison identifies overlooked areas of research which could provide fruitful investigation, such as whether normative assessments of behaviors influence the way that genetic causes are ascribed or endorsed. We also outline the importance of distinguishing reasoning processes regarding genetic causal influences on one's self versus others, as different cognitive processes and biases are likely to be at play.

Biological Criteria of Disease: Four Ways of Going Wrong.

We defend a view of the distinction between the normal and the pathological according to which that distinction has an objective, biological component. We accept that there is a normative component to the concept of disease, especially as applied to human beings. Nevertheless, an organism cannot be in a pathological state unless something has gone wrong for that organism from a purely biological point of view. Biology, we argue, recognises two sources of biological normativity, which jointly generate four "ways of going wrong" from a biological perspective. These findings show why previous attempts to provide objective criteria for pathology have fallen short: Biological science recognizes a broader range of ways in which living things can do better or worse than has previously been recognized in the philosophy of medicine.

Lehrman's dictum: information and explanation in developmental biology.

The integration of concepts from evolutionary developmental biology, such as the homology concept, into developmental psychobiology has great potential. However, evolutionary developmental biology is an attempt to integrate evolutionary and developmental explanation and developmental psychobiology has traditionally been concerned to avoid conflating these two kinds of explanation. This article examines a recent attempt to explain development in terms of "inherited information." The resulting explanation is an evolutionary explanation of development of a kind typical of evolutionary developmental biology. But its proponent mistakes it for an actual developmental explanation. Any integration of evolutionary developmental biology and developmental psychobiology should pay close attention to longstanding concerns about conflating evolutionary and developmental explanations.

Integrating evolutionary, developmental and physiological mismatch.

Contemporary evolutionary medicine has unified the idea of 'evolutionary mismatch', derived from the older idea of 'adaptive lag' in evolution, with ideas about the mismatch in development and physiology derived from the Developmental Origins of Health and Disease (DOHaD) paradigm. A number of publications in evolutionary medicine have tried to make this theoretical framework explicit. The integrative theory of mismatch captures how organisms track environments across space and time on multiple scales in order to maintain an adaptive match to the environment, and how failures of adaptive tracking lead to disease. In this review, we try to present this complex body of theory as clearly and simply as possible with the aim of facilitating its application in new domains. We introduce terminology, which is as far as possible consistent with earlier usage, to distinguish the different forms of mismatch. Mismatch in its modern form is a productive organizing concept that can help researchers articulate how physiology, development and evolution interact with one another and with environmental change to explain health outcomes.

The RNA structure alignment ontology.

Multiple sequence alignments are powerful tools for understanding the structures, functions, and evolutionary histories of linear biological macromolecules (DNA, RNA, and proteins), and for finding homologs in sequence databases. We address several ontological issues related to RNA sequence alignments that are informed by structure. Multiple sequence alignments are usually shown as two-dimensional (2D) matrices, with rows representing individual sequences, and columns identifying nucleotides from different sequences that correspond structurally, functionally, and/or evolutionarily. However, the requirement that sequences and structures correspond nucleotide-by-nucleotide is unrealistic and hinders representation of important biological relationships. High-throughput sequencing efforts are also rapidly making 2D alignments unmanageable because of vertical and horizontal expansion as more sequences are added. Solving the shortcomings of traditional RNA sequence alignments requires explicit annotation of the meaning of each relationship within the alignment. We introduce the notion of "correspondence," which is an equivalence relation between RNA elements in sets of sequences as the basis of an RNA alignment ontology. The purpose of this ontology is twofold: first, to enable the development of new representations of RNA data and of software tools that resolve the expansion problems with current RNA sequence alignments, and second, to facilitate the integration of sequence data with secondary and three-dimensional structural information, as well as other experimental information, to create simultaneously more accurate and more exploitable RNA alignments.

The Case for Basic Biological Research.

The majority of biomedical and biological research relies on a few molecular biology techniques. Here we show that eight key molecular biology techniques would not exist without basic biological research. We also find that the scientific reward system does not sufficiently value basic biological research into molecular mechanisms.

Multispecies individuals.

We assess the arguments for recognising functionally integrated multispecies consortia as genuine biological individuals, including cases of so-called 'holobionts'. We provide two examples in which the same core biochemical processes that sustain life are distributed across a consortium of individuals of different species. Although the same chemistry features in both examples, proponents of the holobiont as unit of evolution would recognize one of the two cases as a multispecies individual whilst they would consider the other as a compelling case of ecological dependence between separate individuals. Some widely used arguments in support of the 'holobiont' concept apply equally to both cases, suggesting that those arguments have misidentified what is at stake when seeking to identify a new level of biological individuality. One important aspect of biological individuality is evolutionary individuality. In line with other work on the evolution of individuality, we show that our cases can be distinguished by focusing on the fitness alignment between the partners of the consortia. We conclude that much of the evidence currently presented for the ubiquity and importance of multi-species individuals is simply not to the point, at least unless the issue of biological individuality is firmly divorced from the question of evolutionary individuality.

Genetic, epigenetic and exogenetic information in development and evolution.

The idea that development is the expression of information accumulated during evolution and that heredity is the transmission of this information is surprisingly hard to cash out in strict, scientific terms. This paper seeks to do so using the sense of information introduced by Francis Crick in his sequence hypothesis and central dogma of molecular biology. It focuses on Crick's idea of precise determination. This is analysed using an information-theoretic measure of causal specificity. This allows us to reconstruct some of Crick's claims about information in transcription and translation. Crick's approach to information has natural extensions to non-coding regions of DNA, to epigenetic marks, and to the genetic or environmental upstream causes of those epigenetic marks. Epigenetic information cannot be reduced to genetic information. The existence of biological information in epigenetic and exogenetic factors is relevant to evolution as well as to development.

Developmental systems theory: what does it explain, and how does it explain it?

We examine developmental systems theory (DST) with two questions in mind: What does DST explain? How does DST explain it? To answer these questions, we start by reviewing major contributions to the origins of DST: the introduction of the idea of a "developmental system", the idea of probabilistic epigenesis, the attention to the role of information in the developmental system, and finally the explicit identification of a DST. We then consider what DST is not, contrasting it with two approaches that have been foils for DST: behavioral genetics and nativist cognitive psychology. Third, we distill out two core concepts that have defined DSTthroughout its history: epigenesis and developmental dynamics. Finally, we turn to how DST explains, arguing that it explains by elucidating mechanisms.

Exploring the folkbiological conception of human nature.

Integrating the study of human diversity into the human evolutionary sciences requires substantial revision of traditional conceptions of a shared human nature. This process may be made more difficult by entrenched, 'folkbiological' modes of thought. Earlier work by the authors suggests that biologically naive subjects hold an implicit theory according to which some traits are expressions of an animal's inner nature while others are imposed by its environment. In this paper, we report further studies that extend and refine our account of this aspect of folkbiology. We examine biologically naive subjects' judgments about whether traits of an animal are 'innate', 'in its DNA' or 'part of its nature'. Subjects do not understand these three descriptions to be equivalent. Both innate and in its DNA have the connotation that the trait is species-typical. This poses an obstacle to the assimilation of the biology of polymorphic and plastic traits by biologically naive audiences. Researchers themselves may not be immune to the continuing pull of folkbiological modes of thought.

Biohumanities: rethinking the relationship between biosciences, philosophy and history of science, and society.

We argue that philosophical and historical research can constitute a "Biohumanities" that deepens our understanding of biology itself engages in constructive "science criticism," helps formulate new "visions of biology," and facilitates "critical science communication." We illustrate these ideas with two recent "experimental philosophy" studies of the concept of the gene and of the concept of innateness conducted by ourselves and collaborators. We conclude that the complex and often troubled relations between science and society are critical to both parties, and argue that the philosophy and history of science can help to make this relationship work.

Genes in the postgenomic era.

We outline three very different concepts of the gene-instrumental, nominal, and postgenomic. The instrumental gene has a critical role in the construction and interpretation of experiments in which the relationship between genotype and phenotype is explored via hybridization between organisms or directly between nucleic acid molecules. It also plays an important theoretical role in the foundations of disciplines such as quantitative genetics and population genetics. The nominal gene is a critical practical tool, allowing stable communication between bioscientists in a wide range of fields grounded in well-defined sequences of nucleotides, but this concept does not embody major theoretical insights into genome structure or function. The post-genomic gene embodies the continuing project of understanding how genome structure supports genome function, but with a deflationary picture of the gene as a structural unit. This final concept of the gene poses a significant challenge to conventional assumptions about the relationship between genome structure and function, and between genotype and phenotype.

Tracking the shift to 'postgenomics'.

Current knowledge about the variety and complexity of the processes that allow regulated gene expression in living organisms calls for a new understanding of genes. A 'postgenomic' understanding of genes as entities constituted during genome expression is outlined and illustrated with specific examples that formed part of a survey research instrument developed by two of the authors for an ongoing empirical study of conceptual change in contemporary biology.