Christoph Rehmann-Sutter

Genes in development : re-reading the molecular paradigm

Introduction / Eva M. Neumann-Held and Christoph Rehmann-Sutter 1 I. Empirical Approaches 1. Genome Analysis and Developmental Biology: The Nematode Caenorhabditis elegans as a Model System / Thomas R. Burglin 15 2. Genes and Form: Inherency in the Evolution of Developmental Mechanisms / Stuart A. Newman and Gerd B. Muller 38 II. Looking Back into History 3. From Genes as Determinants to DNA as Resource: Historical Notes on Development and Genetics / Sahotra Sarkar 77 III. Theorizing Genes 4. The Origin of Species: A Structuralist Approach / Gerry Webster and Brian C. Goodwin 99 5. On the Problem of the Molecular versus the Organismic Approach in Biology / Ulrich Wolf 135 6. Genes, Development, and Semiosis / Jesper Hoffmeyer 152 7. The Fearless Vampire Conservator: Philip Kitcher, Genetic Determinism, and the Informational Gene / Paul E. Griffiths 175 8. Genetics from an Evolutionary Process Perspective / James Griesemer 199 9. Genes-Causes-Codes: Deciphering DNAs Ontological Privilege / Eva M. Newmann-Held 238 10. Boundaries and (Constructive) Interaction / Susan Oyama 272 11. Beyond the Gene but Beneath the Skin / Evelyn Fox Keller 290 12. Poiesis and Praxis: Two Modes of Understanding Development / Christoph Rehmann-Sutter 313 IV. Social and Ethical Implications 13. Developmental Emergence, Genes, and Responsible Science / Brian C. Goodwin 337 14. Nothing Like a Gene / Jackie Leach Scully 349 Contributors 365 Index 369

So, what is an embryo? A comparative study of the views of those asked to donate embryos for hESC research in the UK and Switzerland

The moral status of the human embryo has gained much attention in debates over the acceptability, or otherwise, of human embryonic stem cell research. Far less attention has been paid to the suppliers of those embryos: people who have undergone IVF treatment to produce embryos to assist them to have a baby. It is sociologically and ethically important to understand their views and experiences of being asked to donate embryos for research if we are to fully understand the wider social and regulatory aspects of hESC science. This paper reports on parallel studies investigating these issues in the UK and in Switzerland. The studies reveal the inextricable entangling of the social and moral status of embryos. Since donors participate in different discursive domains and contexts (public, clinic, family) that shape their perception of “what” an embryo is, their views of embryos embody conflicting ideas and ambivalences.

What a wish to die can mean: reasons, meanings and functions of wishes to die, reported from 30 qualitative case studies of terminally ill cancer patients in palliative care

BackgroundDespite research efforts over recent decades to deepen our understanding of why some terminally ill patients express a wish to die (WTD), there is broad consensus that we need more detailed knowledge about the factors that might influence such a wish. The objective of this study is to explore the different possible motivations and explanations of patients who express or experience a WTD.MethodsThirty terminally ill cancer patients, their caregivers and relatives; from a hospice, a palliative care ward in the oncology department of a general hospital, and an ambulatory palliative care service; 116 semi-structured qualitative interviews analysed using a complementary grounded theory and interpretive phenomenological analysis approach.ResultsThree dimensions were found to be crucial for understanding and analysing WTD statements: intentions, motivations and social interactions. This article analyses the motivations of WTD statements. Motivations can further be differentiated into (1) reasons, (2) meanings and (3) functions. Reasons are the factors that patients understand as causing them to have or accounting for having a WTD. These reasons can be ordered along the bio-psycho-socio-spiritual model. Meanings describe the broader explanatory frameworks, which explain what this wish means to a patient. Meanings are larger narratives that reflect personal values and moral understandings and cannot be reduced to reasons. Functions describe the effects of the WTD on patients themselves or on others, conscious or unconscious, that might be part of the motivation for a WTD. Nine typical ‘meanings’ were identified in the study, including “to let death put an end to severe suffering”, “to move on to another reality”, and – more frequently– “to spare others from the burden of oneself”.ConclusionsThe distinction between reasons, meanings and functions allows for a more detailed understanding of the motivation for the WTD statements of cancer patients in palliative care situations. Better understanding is crucial to support patients and their relatives in end-of-life care and decision making. More research is required to investigate the types of motivations for WTD statements, also among non-cancer patients.

'Ambivalence' at the end of life: how to understand patients' wishes ethically.

Health-care professionals in end-of-life care are frequently confronted with patients who seem to be ‘ambivalent’ about treatment decisions, especially if they express a wish to die. This article investigates this phenomenon by analysing two case stories based on narrative interviews with two patients and their caregivers. First, we argue that a respectful approach to patients requires acknowledging that coexistence of opposing wishes can be part of authentic, multi-layered experiences and moral understandings at the end of life. Second, caregivers need to understand when contradictory statements point to tensions in a patient’s moral experience that require support. Third, caregivers should be careful not to negatively label or even pathologize seemingly contradictory patient statements.

The risks of therapeutic misconception and individual patient (n=1) "trials" in rare diseases such as Duchenne dystrophy.

There is currently no cure for Duchenne muscular dystrophy, but there are some promising treatments in development, of which antisense-mediated exon skipping is close to clinical application. The results of the first trials have resulted in significant enthusiasm among clinicians, patients, and their parents and attracted widespread attention in both the scientific and lay press. As in many other rare diseases with significant morbidity this fuels the hope that at last an effective therapy might be within our reach. Parents, but also some clinicians, are now seriously considering treating individual patients with antisense oligonucleotides without waiting for proof from well-designed clinical trials that the new therapies are indeed effective and safe. We understand the sense of urgency that is experienced by patients, parents and their clinicians, but we hope to explain that the preliminary introduction of incompletely tested drugs might lead to dangerous and harmful situations for the patients, endanger the continuation of the development of possible effective therapeutic strategies, or even lead to a complete stop in the further development of promising drugs.There is currently no cure for Duchenne muscular dystrophy, but there are some promising treatments in development, of which antisense-mediated exon skipping is close to clinical application. The results of the first trials have resulted in significant enthusiasm among clinicians, patients, and their parents and attracted widespread attention in both the scientific and lay press. As in many other rare diseases with significant morbidity this fuels the hope that at last an effective therapy might be within our reach. Parents, but also some clinicians, are now seriously considering treating individual patients with antisense oligonucleotides without waiting for proof from well-designed clinical trials that the new therapies are indeed effective and safe. We understand the sense of urgency that is experienced by patients, parents and their clinicians, but we hope to explain that the preliminary introduction of incompletely tested drugs might lead to dangerous and harmful situations for the patients, endanger the continuation of the development of possible effective therapeutic strategies, or even lead to a complete stop in the further development of promising drugs.

How to relate the empirical to the normative: toward a phenomenologically informed hermeneutic approach to bioethics.

In doing ethics we are seeking clarity about situations of ethical difficulty. Sometimes direct practical advice is what we are looking for. This can be advice either for ourselves, for other people, or for the society we live in. Clarification and advice can concern moral issues (what somebody ‘‘ought’’ to do) or issues of aims and preferences (what somebody can desire). In bioethics, both perspectives matter. Complicated situations of decisionmaking in medicine, biological research, or biotechnology raise ethical questions that ideally should be clarified in such a way that the results prove helpful for those who are practically involved, for example, patients, professionals, scientists, supervisors, or regulators (for succinctness, in this article we call all of these ‘‘practitioners’’). We call bioethics ‘‘normative’’ if it works toward recommendations that do not simply describe a field of practice but contain prescriptive elements that say something about what practitioners should do, why they should do so, what they could reasonably aim at, or how they can reach good decisions. In order to provide meaningful advice or helpful clarifications, ethicists must know something about the experiential landscape of the given situation of the practitioner involved. The exploration and understanding of this landscape has become an area of strong interest within ethical methodology; in the words of Sissela Bok:

Genetics, Embodiment and Identity

“Why is it okay to experiment on Homo troglodytes, but not on Homo sapiens?“ — This is the provocative question posed by Jared Diamond at the end of a chapter in which he points out the amazing genetic proximity of chimpanzees and humans. Only 1.6 percent of our DNA is really ‘ours’. ‘The remaining 98.4 percent of our DNA is just normal chimp DNA.” (Diamond (1992); quotes from pp 23 and 31.)

Donating Embryos to Stem Cell Research

This paper is based on linked qualitative studies of the donation of human embryos to stem cell research carried out in the United Kingdom, Switzerland, and China. All three studies used semi-structured interview protocols to allow an in-depth examination of donors’ and non-donors’ rationales for their donation decisions, with the aim of gaining information on contextual and other factors that play a role in donor decisions and identifying how these relate to factors that are more usually included in evaluations made by theoretical ethics. Our findings have implications for one factor that has previously been suggested as being of ethical concern: the role of gratitude. Our empirical work shows no evidence that interpersonal gratitude is an important factor, but it does support the existence of a solidarity-based desire to “give something back” to medical research. Thus, we use empirical data to expand and refine the conceptual basis of bioethically theorizing the IVF–stem cell interface.

Biological organicism and the ethics of the human-nature relationship

Descriptions of living objects represent relationships between those doing the describing and the living objects: describing is performing a relationship. The relationship, and therefore the description, matters ethically. This is explored in this article as a ‘hermeneutic approach’ to the phenomenon of describing.

Guidance in Social and Ethical Issues Related to Clinical, Diagnostic Care and Novel Therapies for Hereditary Neuromuscular Rare Diseases: "Translating" the Translational.

Drug trials in children engage with many ethical issues, from drug-related safety concerns to communication with patients and parents, and recruitment and informed consent procedures. This paper addresses the field of neuromuscular disorders where the possibility of genetic, mutation-specific treatments, has added new complexity. Not only must trial design address issues of equity of access, but researchers must also think through the implications of adopting a personalised medicine approach, which requires a precise molecular diagnosis, in addition to other implications of developing orphan drugs. It is against this background of change and complexity that the Project Ethics Council (PEC) was established within the TREAT-NMD EU Network of Excellence. The PEC is a high level advisory group that draws upon the expertise of its interdisciplinary membership which includes clinicians, lawyers, scientists, parents, representatives of patient organisations, social scientists and ethicists. In this paper we describe the establishment and terms of reference of the PEC, give an indication of the range and depth of its work and provide some analysis of the kinds of complex questions encountered. The paper describes how the PEC has responded to substantive ethical issues raised within the TREAT-NMD consortium and how it has provided a wider resource for any concerned parent, patient, or clinician to ask a question of ethical concern. Issues raised range from science related ethical issues, issues related to hereditary neuromuscular diseases and the new therapeutic approaches and questions concerning patients rights in the context of patient registries and bio-banks. We conclude by recommending the PEC as a model for similar research contexts in rare diseases.