New Modes of Pluralist Global Governance

This paper describes three modes of pluralist global governance. Mode One refers to the creation and proliferation of comprehensive, integrated international regimes on a variety of issues. Mode Two describes the emergence of diverse forms and sites of cross-national decision making by multiple actors, public and private as well as local, regional and global, forming governance networks and “regime complexes,” including the orchestration of new forms of authority by international actors and organizations. Mode Three, which is the main focus of the paper, describes the gradual institutionalization of practices involving continual updating and revision, open participation, an agreed understanding of goals and practices, and monitoring, including peer review. We call this third mode Global Experimentalist Governance. Experimentalist Governance arises in situations of complex interdependence and pervasive uncertainty about causal relationships. Its practice is illustrated in the paper by three examples: the arrangements devised to protect dolphins from being killed by tuna fishing practices; the U.N. Convention on the Rights of Persons with Disabilities; and the Montreal Protocol on the Ozone Layer. Experimentalist Governance tends to appear on issues for which governments cannot formulate and enforce comprehensive sets of rules, but which do not involve fundamental disagreements or high politics, and in which civil society is active. The paper shows that instances of Experimentalist Governance are already evident in various global arenas and issue areas, and argues that their significance seems likely to grow

New Modes of Pluralist Global Governance

This paper describes three modes of pluralist global governance. Mode One refers to the creation and proliferation of comprehensive, integrated international regimes on a variety of issues. Mode Two describes the emergence of diverse forms and sites of cross-national decision making by multiple actors, public and private as well as local, regional and global, forming governance networks and “regime complexes,” including the orchestration of new forms of authority by international actors and organizations. Mode Three, which is the main focus of the paper, describes the gradual institutionalization of practices involving continual updating and revision, open participation, an agreed understanding of goals and practices, and monitoring, including peer review. We call this third mode Global Experimentalist Governance. Experimentalist Governance arises in situations of complex interdependence and pervasive uncertainty about causal relationships. Its practice is illustrated in the paper by three examples: the arrangements devised to protect dolphins from being killed by tuna fishing practices; the U.N. Convention on the Rights of Persons with Disabilities; and the Montreal Protocol on the Ozone Layer. Experimentalist Governance tends to appear on issues for which governments cannot formulate and enforce comprehensive sets of rules, but which do not involve fundamental disagreements or high politics, and in which civil society is active. The paper shows that instances of Experimentalist Governance are already evident in various global arenas and issue areas, and argues that their significance seems likely to grow

100,000 Genomes Pilot on Rare-Disease Diagnosis in Health Care - Preliminary Report.

BACKGROUND: The U.K. 100,000 Genomes Project is in the process of investigating the role of genome sequencing in patients with undiagnosed rare diseases after usual care and the alignment of this research with health care implementation in the U.K. National Health Service. Other parts of this project focus on patients with cancer and infection. METHODS: We conducted a pilot study involving 4660 participants from 2183 families, among whom 161 disorders covering a broad spectrum of rare diseases were present. We collected data on clinical features with the use of Human Phenotype Ontology terms, undertook genome sequencing, applied automated variant prioritization on the basis of applied virtual gene panels and phenotypes, and identified novel pathogenic variants through research analysis. RESULTS: Diagnostic yields varied among family structures and were highest in family trios (both parents and a proband) and families with larger pedigrees. Diagnostic yields were much higher for disorders likely to have a monogenic cause (35%) than for disorders likely to have a complex cause (11%). Diagnostic yields for intellectual disability, hearing disorders, and vision disorders ranged from 40 to 55%. We made genetic diagnoses in 25% of the probands. A total of 14% of the diagnoses were made by means of the combination of research and automated approaches, which was critical for cases in which we found etiologic noncoding, structural, and mitochondrial genome variants and coding variants poorly covered by exome sequencing. Cohortwide burden testing across 57,000 genomes enabled the discovery of three new disease genes and 19 new associations. Of the genetic diagnoses that we made, 25% had immediate ramifications for clinical decision making for the patients or their relatives. CONCLUSIONS: Our pilot study of genome sequencing in a national health care system showed an increase in diagnostic yield across a range of rare diseases. (Funded by the National Institute for Health Research and others.)