Society and synthetic cells:A position paper by the Future Panel on Synthetic Life

The BaSyC consortium, whose acronym stands for building a synthetic cell, proposes to develop a synthetic cell from the bottom up. In the context of this joined effort, the Rathenau Instituut and Radboud University Nijmegen have organised the Future Panel on Synthetic Life, consisting of societal experts, to explore the social challenges, dilemmas, and possible societal impacts of synthetic cell research, and to advise how this research may contribute to a fair and sustainable future. The goal for the Future Panel is to create an initial agenda for future political, academic, and public debate on the synthetic cell.The profile of science and technology is two-sided. On the one hand, they act as drivers for problem-solving, progress, and emancipation, but techno-scientific innovation can also give rise to disruptive threats. Therefore, societal reflection should be timely and anticipatory. Rather than asking what risks and benefits are involved, the question will be how to engage society in such a way that synthetic cell research can become a joint endeavour, responsive to societal hopes and concerns. Consequently, the Future Panel aimed to:• map the social challenges and dilemmas in a society where a synthetic cell exists;• identify conditions under which synthetic cell technology can be considered beneficial for society; and• advice on how these conditions can be realised.To contribute to this, the Future Panel discussed the role and perspectives of key stakeholders (academia, government and governance, industry, and civil society), besides more specific issues like public responses, biosafety, biosecurity, and intellectual property rights during multiple online and offline meetings within a period of two years. This position paper summarises the most important points of conversation, shared insights, key challenges, dilemmas that were discussed during these meetings, resulting in four recommendations, as a starting point for further analysis and debate.Key challengesDuring the deliberations, the Future Panel encountered four overarching challenges.1. The novelty of synthetic cell research makes it challenging to devise amethodology capable of anticipating public concerns in a domain where overt public attitudes do not exist as of yet.Society and synthetic cells 132. As long as the existing power structures within the contexts that shape developments in science and technology are not explicitly addressed, the development of a synthetic cell will inevitably reproduce and may even strengthen existing power inequalities.3. In order to involve civil society and allow citizens to articulate their views and concerns, besides factual information, the synthetic cell has to be positioned in a proper context: how to develop a responsible narrative that allows the public to actively relate to these developments?4. Even though the BaSyC project is halfway, there are still many unknowns, even unknown unknowns. A key challenge is to connect social, ethical, and science perspectives, and dilemmas, ambitions, and uncertainties related to the building of a synthetic cell.DilemmasDuring the panel discussions, many reasons have arisen, from different perspectives, for involving the general public, governments, industry and NGOs in an anticipatory way. However, doing this reveals some fundamental dilemmas and tensions that should be addressed.1. The BaSyC project is curiosity-driven, aspiring to deepen our understanding of life. At the same time, our desire to know is driven by an impetus to control. How to practice synthetic cell research as a dialogue with nature rather than an appropriation and instrumentalisation of the living cell?2. Many aspects of synthetic cell research are yet unknown. How to allow space for the unknown while, at the same time, opt for an anticipatory and imaginative approach to take the future social and ethical implications and concerns into account?3. How to make research more inclusive by involving public, politics and policy in such a way that it is fostering and inspirational rather than detrimental for curiosity-driven experimentation and exploration?4. Curiosity-driven science requires a great deal of specialism and thrives on serendipity. How to achieve convergence in science, involving multiple stakeholders and taking into account societal expectations and concerns, without frustrating the process of discovery?5. Deliberation requires a dialogue across disciplines, languages, and levels of information. How to combine different vocabularies, perspectives, socio- cultural and time horizons in a meaningful way?6. Within science and technology, and in particular biotechnology, there has long been a discussion about how to deal with knowledge and intellectual property rights. Should life be considered patentable or should life be seen as a common heritage that belongs to everybody?7. How to deal with researchers who need to make their work openly accessible, and companies, incubators, and organisations that want to protect their invention?8. Within projects of four to five years, researchers are under pressure to focus on and deliver scientific publications, while at the same time being encouraged to actively reflect on and engage with the potential societal impact of their work. How to balance conflicting expectations related to different time horizons?RecommendationsThe Future Panel proposes four recommendations for fostering a socially responsible development of the synthetic cell:1. Ensure that the synthetic cell contributes to a fair and sustainable futureTo foster sustainable synthetic cells, we need co-constructed narratives that allow us to explore how synthetic cells may contribute to a sustainable future. It is not enough to stimulate techno-scientific innovation as such. Governments must simultaneously stimulate social innovation, and promote broad stakeholder involvement in synthetic cell research.2. Organise participation of civil society in synthetic cell researchIn order to ensure that synthetic cell research contributes to a fair and sustainable society, an inclusive and participatory process of reflection is required, open to public intelligence, and sensitive to societal expectations and concerns. This requires innovative methods to engage the wisdom of the crowd. Meetings with societal stakeholders should be organised on relevant issues at different moments of the project and should be designed as in-between spaces in which different meanings, interests, and societal values come together and are made explicit.3. Foster a socially responsive academic ecosystemRather than endorsing the status quo, synthetic cell research emphasises the importance of rethinking the university of the 21st century, where research and education must become more inclusive and interactive, bent on developing long- term partnerships with society: with industry and governmental organisations, but first and foremost with society at large. Societal reflection and interaction with society should be an integral part of academic research and education. Therefore, researchers must be empowered to engage with society in such a way that dialogue and interaction become an inherent part of their work, from design to publication.4. Design social governance experiments aimed at renewing the regulatory landscape for new biotechnologies, including the synthetic cellEnsuring that the synthetic cell may contribute to a more sustainable and socially equitable world requires an adequate social understanding of governance and regulatory systems. The current regulatory system is not prepared for that task. We need a new system, which does not reproduce previous polemics. Besides looking at risks, a more comprehensive regulatory regime would integrate questions concerning sustainability, human rights, ethics, and societal desirability. Governance experiments co-designed with societal actors are needed to gain insight into the contours of such a new regulatory landscape on synthetic biology or new biotechnologies, including the synthetic cell

Hallmarks of Aromatase Inhibitor Drug Resistance Revealed by Epigenetic Profiling in Breast Cancer

Aromatase inhibitors are the major first-line treatment of estrogen receptor-positive breast cancer, but resistance to treatment is common. To date, no biomarkers have been validated clinically to guide subsequent therapy in these patients. In this study, we mapped the genome-wide chromatin-binding profiles of estrogen receptor alpha (ER alpha), along with the epigenetic modifications H3K4me3 and H3K27me3, that are responsible for determining gene transcription (n = 12). Differential binding patterns of ER alpha, H3K4me3, and H3K27me3 were enriched between patients with good or poor outcomes after aromatase inhibition. ER alpha and H3K27me3 patterns were validated in an additional independent set of breast cancer cases (n = 10). We coupled these patterns to array-based proximal gene expression and progression-free survival data derived from a further independent cohort of 72 aromatase inhibitor-treated patients. Through this approach, we determined that the ER alpha and H3K27me3 profiles predicted the treatment outcomes for first-line aromatase inhibitors. In contrast, the H3K4me3 pattern identified was not similarly informative. The classification potential of these genes was only partially preserved in a cohort of 101 patients who received first-line tamoxifen treatment, suggesting some treatment selectivity in patient classification. (C) 2013 AACR

Virology Experts in the Boundary Zone Between Science, Policy and the Public: A Biographical Analysis

This article aims to open up the biographical black box of three experts working in the boundary zone between science, policy and public debate. A biographical-narrative approach is used to analyse the roles played by the virologists Albert Osterhaus, Roel Coutinho and Jaap Goudsmit in policy and public debate. These figures were among the few leading virologists visibly active in the Netherlands during the revival of infectious diseases in the 1980s. Osterhaus and Coutinho in particular are still the key figures today, as demonstrated during the outbreak of novel influenza A (H1N1). This article studies the various political and communicative challenges and dilemmas encountered by these three virologists, and discusses the way in which, strategically or not, they handled those challenges and dilemmas during the various stages of the field’s recent history. Important in this respect is their pursuit of a public role that is both effective and credible. We will conclude with a reflection on the H1N1 pandemic, and the historical and biographical ties between emerging governance arrangements and the experts involved in the development of such arrangements

Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors

Background Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders. Methods We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors. Results Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged. Conclusions Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.Peer reviewe

Identification of multiple risk loci and regulatory mechanisms influencing susceptibility to multiple myeloma

Genome-wide association studies (GWAS) have transformed our understanding of susceptibility to multiple myeloma (MM), but much of the heritability remains unexplained. We report a new GWAS, a meta-analysis with previous GWAS and a replication series, totalling 9974 MM cases and 247,556 controls of European ancestry. Collectively, these data provide evidence for six new MM risk loci, bringing the total number to 23. Integration of information from gene expression, epigenetic profiling and in situ Hi-C data for the 23 risk loci implicate disruption of developmental transcriptional regulators as a basis of MM susceptibility, compatible with altered B-cell differentiation as a key mechanism. Dysregulation of autophagy/apoptosis and cell cycle signalling feature as recurrently perturbed pathways. Our findings provide further insight

The need and availability of support systems for physicians involved in a serious adverse event

Objective: Serious adverse events occur in healthcare, and do not solely have consequences for patients (first victims), but also affect physicians involved (second victims). These second victims experience diminished emotional well-being and less professional performance. An increasing number of hospitals organize support for second victims, although scientific evidence on the kind of support that is expected and needed is poor. This study therefore investigates support needs after serious adverse events from both personal (physicians) and organizational (quality and safety staff members) perspectives. Methods: We conducted semi-structured interviews in a Dutch university medical center. Physicians (N = 19) who had been directly involved in a serious adverse event participated. In addition, quality and safety staff members (N = 3) reflected on the support needs as expressed by physicians. Verbatim transcripts were three fold coded, which led to several themes for our inductive thematic analysis. Results: Contrary to recent developments in healthcare organizations, participants did not plea for a hospital-wide support team. Acceptance of the emotional and professional impact of an adverse event by direct colleagues and supervisors is more important. Where such a cultural context is provided, physicians prefer support of a close and reliable colleague to cope with emotions and doubts, a supervisor who monitors recovery, and a healthcare organization that provides information about required procedures to learn from the events. However, this ideal was seldom found in the competitive working environment. This underlines the need for a shift from a competitive professional culture into a more supportive one. Conclusions: Ideally, direct colleagues support each other after an adverse event. This form of collegial support can only be successful if there is general acceptance of healthcare professionals’ vulnerability and their support needs within the direct working environment. To create the right circumstances to meet these support needs, both healthcare professionals and hospital organizations have to recognize and take their responsibilities

The need and availability of support systems for physicians involved in a serious adverse event

Objective: Serious adverse events occur in healthcare, and do not solely have consequences for patients (first victims), but also affect physicians involved (second victims). These second victims experience diminished emotional well-being and less professional performance. An increasing number of hospitals organize support for second victims, although scientific evidence on the kind of support that is expected and needed is poor. This study therefore investigates support needs after serious adverse events from both personal (physicians) and organizational (quality and safety staff members) perspectives. Methods: We conducted semi-structured interviews in a Dutch university medical center. Physicians (N = 19) who had been directly involved in a serious adverse event participated. In addition, quality and safety staff members (N = 3) reflected on the support needs as expressed by physicians. Verbatim transcripts were three fold coded, which led to several themes for our inductive thematic analysis. Results: Contrary to recent developments in healthcare organizations, participants did not plea for a hospital-wide support team. Acceptance of the emotional and professional impact of an adverse event by direct colleagues and supervisors is more important. Where such a cultural context is provided, physicians prefer support of a close and reliable colleague to cope with emotions and doubts, a supervisor who monitors recovery, and a healthcare organization that provides information about required procedures to learn from the events. However, this ideal was seldom found in the competitive working environment. This underlines the need for a shift from a competitive professional culture into a more supportive one. Conclusions: Ideally, direct colleagues support each other after an adverse event. This form of collegial support can only be successful if there is general acceptance of healthcare professionals’ vulnerability and their support needs within the direct working environment. To create the right circumstances to meet these support needs, both healthcare professionals and hospital organizations have to recognize and take their responsibilities

Design of a 15-month interprofessional workplace learning program to expand the added value of clinical pharmacists in primary care

BACKGROUND AND PURPOSE: Clinical pharmacists who work in the general practice settings bring an improvement to patient care and outcomes. Postgraduate training for an independent clinical role does not often occur in the primary health care setting. When it does, the design of the curriculum is infrequently based on interprofessional workplace learning principles and it does not always integrate practical experience with classroom-based learning activities. This could lead to situations where clinical pharmacists are insufficiently trained to apply clinical reasoning skills and direct patient care in the general practice setting. EDUCATIONAL ACTIVITY AND SETTING: A program was designed, including competencies and learning objectives, based on results from focus group interviews with stakeholders and the literature on interprofessional workplace learning. Ten participants were selected for a pilot run of the program and were asked several times for their opinion about the program. FINDINGS: A 15-month training program was offered to pharmacists who became clinical pharmacists with the responsibility to perform patient consultations in general practice. The program was based on interprofessional workplace learning principles and facilitated the participants' skill in connecting the evidence, the patients' perspective and their own professional perspective. The 10 participating pharmacists were satisfied with the program. DISCUSSION AND SUMMARY: The training program provided increased opportunities to clinical pharmacists to add value in general practice. The training program enabled pharmacists to advance their skills in direct patient care and to improve the alignment between different professionals in the primary care domain