Global Genes Local Concerns

The interdisciplinary project design of Global Genes – Local Concerns featured three biobanking and genomic screening models. Biological samples collected in e.g. Denmark and Pakistan have been (and are being) genetically screened with next generation sequencing methods, with a focus to identify mutated novel cilia- and centrosome-related genes that represent novel ciliopathy candidates, but have not yet been coupled to a disease. This biological/genetic focus was chosen since ciliopathies are pleiotropic causing dysfunction of a variety of organs. Genes encoding the ciliome constitute 1/20 of the human genome, but the number of known ciliopathies is still <100. The individual ciliopathy will likely be an orphan disorder, but will frequently have implications for phenotypically overlapping common complex disorders. Moreover, since the cilium proteome is known, targeted approaches can be used to identify candidate disease genes and study their function.

Simultaneously, these models served as cases for studies of donor motivation, stakeholder attitudes/concerns and legal/commercialization issues to identify concrete barriers for cross-national biobank based research and utilization of research results.

The project furthermore analyzed how biobanks contributed to translational research in Denmark and abroad; opportunities and challenges for the regulation of translational use of biobanks; how inter-biobank coordination and collaboration occurred on various levels; and how academic and industrial exploitation, ownership and IPR issues was facilitated and addressed.

We have addressed the schism between the international character of the cooperation and the territorial nature of the legislation, by the inclusion of vulnerable donor populations in Pakistan. Pakistan was interesting also because of the high degree of illiteracy contradicts the general rule of written informed consent put forward as essential in codes of conduct governing international collaboration.

Based on interdisciplinarity this project has worked to develop and embed new guidelines in a university setting. This will make UCPH a progressive contributor to the already existing unique Danish biobank infrastructure.

List of participants - Global Genes Local Concerns

The project dealt with legal, ethical and scientific challenges in cross-national biobanking and translational exploitation. Concentrating on biobanking in a university setting, the project aimed to identify and ultimately overcome regulatory barriers to biobank research and the utilization of research results, while at the same time securing the ethical legitimacy of the research and the societal interests in access to information and innovation. To achieve this goal, the project have combined legal, bioethical, and social science perspectives with human genetic studies that involved patient material from multiple countries.

The full report can be downloaded here (pdf).

Appendix A. List of Publications (pdf)

Appendix A. List of Publications (pdf)

• Dr. Shahid Mahmood Baig, Group Leader and Principal Scientist, Human Molecular Genetics Laboratory, Health Biotechnology Division, National Institute for Biotechnology and Genetic Engineering, (NIBGE), Faisalabad, Pakistan
• Peter Jacky, PhD, Director Emeritus, Cytogenetics/Molecular Genetics at Northwest Permanente, P.C., Portland, OR, USA
• D.Soc.Sc Aaro Tupasela, Finland
• Alex Postma, Amsterdam Medical Center, The Netherlands
• Jens Andersen, Univ. Southern Denmark, Odense, Denmark
• Dominic P. Norris, MRC Mammalian Genetics Unit, Harwell Science and Innovation Campus, Oxfordshire, United Kingdom

The goal of the work package on collection was to explore and trace donor and collaborator interests at multiple sites internationally during the process of collecting and setting up of a biobank in Denmark. Interviewing stakeholders alongside the recruitment of participants and collection of samples in Denmark, Pakistan and the USA we sought to develop comparative empirical data (both qualitative and quantitative) on participant motivations, expectations and concerns.

We would conduct semi-structures interviews with donors, clinicians, researchers, as well as other collaborators involved in the acquisition of samples and information. Focusing on the motivations, interests, hopes and concerns of these stakeholders an empirically grounded comparative understanding could be developed. Given the differences in the locations and contexts of collection we would devise methods and tools that could be used and applied in order to take into account stakeholder concerns and motivation. Using this approach, the work package would contribute to identifying areas of conflict of interest among stakeholders that needed to be addressed to ensure donor confidence and long-term sustainable collaborator relationships.

Biological samples collected in Pakistan, in the US and in other countries would be genetically screened with next generation sequencing methods, with a focus to identify mutated novel cilia- and centrosome-related genes that represent novel ciliopathy candidates, but have not yet been coupled to a disease. This biological/genetic focus was chosen since the ciliome constitute 1/20 of the human proteome, the number of known ciliopathies was still <100, but involved disorders affecting a variety of organs and dysfunctions; the individual ciliopathy would likely be an orphan disorder, but would frequently have implications for phenotypically overlapping common complex disorders, and the functional studies of the genes/proteins could be systematized.

Read more about Biobanking – genetic screening - Work package 2

This work package addressed the biological function of identified candidate disease genes, plus hitherto uncharacterized genes known to be associated with cilia and centrosomes using mouse and human cell cultures as well as zebrafish and mouse models with live cell and tissue imaging methods, transcriptomics and proteomic approaches.

Read more about Functional analysis - Work package 3 : Functional analysis of candidate disease genes

The commercialization part of WP 4 analyzed which organisational and legislative choices biobanking could involve and whether publicly funded biobanks should engaging in tech-transfer and the protection of research results through i.a. IPRs. Besides providing insights that would re-emerge in WP6, special emphasis would be laid on interconnecting WP4 with WP2 and WP3. In particular the WP would discuss the potential consequences of direct involvement in downstream IPRs for publicly funded biobanks and consider alternate policy choices to strike a balance between the interests of the different stakeholders. Thus the legal part would also discuss alternative strategies in response to IPR concerns, such as mechanism to prevent exclusive licensing (as required by most IPR holders), contract-obligations to return research results to the biobank and making optimal use of the research exemption. This would provide the basis for further investigations directed to e.g. new collaborative models of innovation such as public-private partnerships, open-source sharing or other new models for the commercialization and translational exploitation of biobanks. Thus, the analysis would discuss de lege ferenda possibilities based on the legal status quo, apart from traditional legal analysis to determine various choices under the present state of the law.

To achieve a critical evaluation and analysis of the existing norms and institutions, this would also entail the use of comparative analysis to identify and discuss international variations in terms of the legal positions and justifications and the exploitation of a law & technology approach, in order to describe scientific developments and evaluate their impact on IPR protection and regulation of biobanking. This would i.a. involve discussions of how legal and scientific developments had contributed to the current “paradigm shift” in pharmaceutical R&D and how this in turn affected biobank-related debates and choices. This might also have resulted in more specific discussions of topical issues, including the role the biobanks play in personalized medicine, developing treatments for orphan diseases or in other specific areas of translational exploitation.

The aim of WP5 was to address certain specific ethical challenges arising from biobanks operating across boundaries of diverse ethical norms and values. The focus would be on the collection of samples planned in WP2 in Pakistan, and the specific ethical challenges that this would generate for various stakeholders.

We would focus especially on areas where no guidelines existed, or where there was a culturally dependent plurality of interpretations of guidelines. We expected to find such diversities regarding the interpretation of the requirements of informed consent and in norms regarding how potential benefits of biobanks should be used. In addition, there was likely to be issues about stigmatization of vulnerable populations, gender and group identities.

Read more about Ethical Framework - Work package 5

The aim of the guidelines was to optimize the efficiency and quality of cross-border biobanking by capturing the concrete results of WP1, WP4 and WP5 in order to provide an instrument that could provide concrete and ethically and legally sound guidance in biobanking projects generally.

The precise character of the guidelines would vary. They might be taking the form of questions that should be considered or how to develop local best practices (e.g. for compiling a questionnaire to be used by illiterate donors), and sometimes they might be taking the form of a “standard contract” (e.g. an MTA) or providing general background information which could be used in future rule- or decision making (e.g. on the different routes for applying for patents).

(leader: Jens Schovsbo (LAW). Participants; Janne R. Herrmann, Timo Minssen (LAW); Klemens Kappel, Morten Ebbe Juul Nielsen (HUM); Klaus Hoeyer, Niels Tommerup, Lars Allan Larsen, Klaus W. Kjær (HEALTH); Søren T. Christensen, Lotte B. Pedersen, Karsten Kristiansen, Jun Wang, Peter Sandøe (SCIENCE)).