Non-safety Assessments of Genome-Edited Organisms: Should They be Included in Regulation?

This article presents and evaluates arguments supporting that an approval procedure for genome-edited organisms for food or feed should include a broad assessment of societal, ethical and environmental concerns; so-called non-safety assessment. The core of analysis is the requirement of the Norwegian Gene Technology Act that the sustainability, ethical and societal impacts of a genetically modified organism should be assessed prior to regulatory approval of the novel products. The article gives an overview how this requirement has been implemented in the regulatory practice, demonstrating that such assessment is feasible and justified. Even in situations where genome-edited organisms are considered comparable to non-modified organisms in terms of risk, the technology may have-in addition to social benefits-negative impacts that warrant assessments of the kind required in the Act. The main reason is the disruptive character of the genome editing technologies due to their potential for novel, ground-breaking solutions in agriculture and aquaculture combined with the economic framework shaped by the patent system. Food is fundamental for a good life, biologically and culturally, which warrants stricter assessment procedures than what is required for other industries, at least in countries like Norway with a strong tradition for national control over agricultural markets and breeding programs.

DNA Vaccines: Regulatory Considerations and Safety Aspects.

DNA vaccines have great potential as preventive or therapeutic vaccines against viral, bacterial, or parasitic diseases as well as cancer, and may also be used as gene therapy products. Although many human and veterinary DNA vaccines have been investigated in laboratory trials, only four of these have been approved for commercial use. In this paper an overview of the regulatory requirements for the development of DNA vaccines is given. The regulatory process in EU and USA is described. A discussion concerning the relevance of national regulations on gene technology is included. In addition the main safety concerns associated with DNA vaccines, relating to unwanted side effects in the vaccinated mammal or fish, are presented. Finally, the need for greater openness regarding the assessment information is discussed.

We have never been ELSI researchers - there is no need for a post-ELSI shift.

This article criticizes recent suggestions that the current ELSI research field should accommodate a new direction towards a 'post-ELSI' agenda. Post-ELSI research seeks to avoid the modernist division of responsibility for technical and social issues said to characterize ELSI research. Collaboration and integration are consequently the key terms of post-ELSI strategies that are to distinguish it from ELSI strategies. We argue that this call for a new direction relies on an inadequate generalized analysis of ELSI research as modern that will affect the construal of post-ELSI strategies. We are concerned that the call for post-ELSI shift will exclude imaginative proposals and intellectual freedom by narrowing down the scope and methodologies of ELSI and thereby missing opportunities to play a critical and constructive normative role. Instead of framing current trends in ELSI research as a radical and progressive shift from ELSI to post-ELSI, we suggest an alternative story of expansion and diversification described in terms of a drift from ELSA 1 to ELSA 2, pertaining to acronyms in use in Europe. ELSI research has never been modern. It has been experimenting from the very start on ways to mesh the works of humanist, social and natural scientist in order to bridge and build alignments of emerging scientific and societal goals and matters of concern. The development from ELSA 1 to ELSA 2 expands in our account the range of intellectual and methodological capacities of analysis and engagement of complex and dynamic science-society relationships. We present three areas of ELSA expertise to illustrate that the expertise within the field builds on scholarly achievements within the humanities, social sciences as well as the natural sciences. The plurality of disciplinary background of ELSA researchers represents a valuable diversity that enables mutual criticism and formulations of complementary approaches that together constitute a viable ELSA field.

Scientific dishonesty--a nationwide survey of doctoral students in Norway.

BACKGROUND: The knowledge of scientific dishonesty is scarce and heterogeneous. Therefore this study investigates the experiences with and the attitudes towards various forms of scientific dishonesty among PhD-students at the medical faculties of all Norwegian universities. METHOD: Anonymous questionnaire distributed to all post graduate students attending introductory PhD-courses at all medical faculties in Norway in 2010/2011. Descriptive statistics. RESULTS: 189 of 262 questionnaires were returned (72.1%). 65% of the respondents had not, during the last year, heard or read about researchers who committed scientific dishonesty. One respondent had experienced pressure to fabricate and to falsify data, and one had experienced pressure to plagiarize data. On average 60% of the respondents were uncertain whether their department had a written policy concerning scientific conduct. About 11% of the respondents had experienced unethical pressure concerning the order of authors during the last 12 months. 10% did not find it inappropriate to report experimental data without having conducted the experiment and 38% did not find it inappropriate to try a variety of different methods of analysis to find a statistically significant result. 13% agreed that it is acceptable to selectively omit contradictory results to expedite publication and 10% found it acceptable to falsify or fabricate data to expedite publication, if they were confident of their findings. 79% agreed that they would be willing to report misconduct to a responsible official. CONCLUSION: Although there is less scientific dishonesty reported in Norway than in other countries, dishonesty is not unknown to doctoral students. Some forms of scientific misconduct are considered to be acceptable by a significant minority. There was little awareness of relevant policies for scientific conduct, but a high level of willingness to report misconduct.

Mapping Uncertainties in the Upstream: The Case of PLGA Nanoparticles in Salmon Vaccines.

The diversity of nanotechnologies and of the governance challenges that their applications raise calls for exploration and learning across different cases. We present an Upstream Oversight Assessment (UOA) of expected benefits and potential harms of nanoparticles made of a synthetic polymer (PLGA) to improve vaccines for farmed salmon. Suggested by Jennifer Kuzma and colleagues, an UOA may help identify and prioritise research needs, and it may support evaluations of the adequacy of relevant existing regulatory frameworks. In this work, the UOA approach is modified and supported with elements from the uncertainty analysis framework developed by Warren Walker and colleagues. Empirically, we draw on relevant available published literature and insights generated in an ongoing nanoparticle salmon vaccine project, in which one of the authors participates. Nanotechnologies have not previously been encountered in the regulatory context of fish vaccines, which in part raises unique challenges due to prospective large scale vaccine use in semi-open aquatic systems. Strengthened through cooperation between ELSA and technology researchers we found the UOA useful for an early mapping of benefits and concerns, and for identifying areas in need of further research prior to a nanoparticle based salmon vaccine is developed and taken into use. We consider our approach to represent one among several complementing initiatives that seek to contribute to early stage evaluations of possible negative side effects, broadly conceived, in order to facilitate a more robust nanotechnology development.

Precaution or Integrated Responsibility Approach to Nanovaccines in Fish Farming? A Critical Appraisal of the UNESCO Precautionary Principle.

Nanoparticles have multifaceted advantages in drug administration as vaccine delivery and hence hold promises for improving protection of farmed fish against diseases caused by pathogens. However, there are concerns that the benefits associated with distribution of nanoparticles may also be accompanied with risks to the environment and health. The complexity of the natural and social systems involved implies that the information acquired in quantified risk assessments may be inadequate for evidence-based decisions. One controversial strategy for dealing with this kind of uncertainty is the precautionary principle. A few years ago, an UNESCO expert group suggested a new approach for implementation of the principle. Here we compare the UNESCO principle with earlier versions and explore the advantages and disadvantages by employing the UNESCO version to the use of PLGA nanoparticles for delivery of vaccines in aquaculture. Finally, we discuss whether a combined scientific and ethical analysis that involves the concept of responsibility will enable approaches that can provide a supplement to the precautionary principle as basis for decision-making in areas of scientific uncertainty, such as the application of nanoparticles in the vaccination of farmed fish.

Detection of supercoiled plasmid DNA and luciferase expression in Atlantic salmon (Salmo salar L.) 535 days after injection.

In this study our aim was to investigate the persistence and distribution of plasmid DNA in Atlantic salmon. Atlantic salmon (mean weight 70 g) were injected with 100 microg of plasmid DNA in 100 microl of phosphate buffered saline. The fish were reared in running fresh water at temperature 0-12 degrees C and injections were performed at 8 degrees C. After intramuscular injection, samples were obtained from blood and different tissues and organs up to day 535 after injection. We found by use of Southern blotting open circular and supercoiled plasmid DNA at the injection site and plasmid DNA fragments, assessed by real-time PCR, were detected in some of the examined tissues up to day 535. A co-persistence of luciferase transcript and activity were identified at the injection site up to day 535, however analysis of DAM methylation pattern suggested that the plasmid DNA did not replicate in vivo. Our study indicated that the plasmid DNA can persist for a prolonged time after intramuscular injection.