Precaution,threshold risk and public deliberation

It has been argued that the precautionary principle is incoherent and thus useless as a guide for regulatory policy. In a recent paper in Bioethics, Wareham and Nardini propose a response to the ‘precautionary paradox’ according to which the precautionary principle's usefulness for decision making in policy and regulation contexts can be justified by appeal to a probability threshold discriminating between negligible and non‐negligible risks. It would be of great significance to debates about risk and precaution if there were a sound method for determining a minimum probability threshold of negligible risk. This is what Wareham and Nardini aim to do. The novelty of their approach is that they suggest that such a threshold should be determined by a method of public deliberation. In this article I discuss the merits of Wareham and Nardini’s public deliberation method for determining thresholds. I raise an epistemic worry about the public deliberation method they suggest, and argue that their proposal is inadequate due to a hidden assumption that the acceptability of a risk can be completely analysed in terms of its probability.     

Queueing up for enzymatic processing: correlated signaling through coupled degradation

High‐throughput technologies have led to the generation of complex wiring diagrams as a post‐sequencing paradigm for depicting the interactions between vast and diverse cellular species. While these diagrams are useful for analyzing biological systems on a large scale, a detailed understanding of the molecular mechanisms that underlie the observed network connections is critical for the further development of systems and synthetic biology. Here, we use queueing theory to investigate how ‘waiting lines’ can lead to correlations between protein ‘customers’ that are coupled solely through a downstream set of enzymatic ‘servers’. Using the E. coli ClpXP degradation machine as a model processing system, we observe significant cross‐talk between two networks that are indirectly coupled through a common set of processors. We further illustrate the implications of enzymatic queueing using a synthetic biology application, in which two independent synthetic networks demonstrate synchronized behavior when common ClpXP machinery is overburdened. Our results demonstrate that such post‐translational processes can lead to dynamic connections in cellular networks and may provide a mechanistic understanding of existing but currently inexplicable links.     

Playing God and tampering with nature: popular labels for real concerns in synthetic biology

Public engagement in science with diverse cross-sections of the community is considered a critical aspect of responsible biotechnological innovation. While the research community shows willingness to engage with both ambivalent and supportive audiences about potentially disruptive technological advances, there is less enthusiasm for engaging with groups who hold deeply opposing views to such advances. ‘Playing God’ and ‘tampering with nature’ are popular examples of intrinsic objections often made in opposition to the development or use of novel genetic technologies. Historically appearing in arguments against the pursuit of genetically modified organisms in agriculture and food industries, intrinsic objections have previously been labelled by the science community as inconsistent, non-scientific, and vague. Now found in a range of innovation contexts, the domain of synthetic biology appears to attract such objections consistently. We present the findings from a large Australian study (N?=?4593) which suggests ‘playing God’ objections and their variants can be multilayered and, at times, accompanied by meaningful information about risk perceptions. We use qualitative analysis of open-ended responses from an online survey to show how these objections are articulated in response to selected synthetic biology applications across environmental and health domains. Our research invites a rethink of how the synthetic biology community perceives, and engages with, people who express intrinsic objections. These people may additionally hold extrinsic concerns that may be potentially addressed, or at least reasonably considered, through dialogue. We offer some concluding remarks for engaging with publics who employ these types of arguments to communicate unease with aspects of technology development and use.

     

Germline gene editing and the precautionary principle

The precautionary principle aims to influence decision-making in contexts where some activity poses uncertain but potentially grave threats. This perfectly describes the controversy surrounding germline gene editing. This article considers whether the precautionary principle should influence how we weigh the risks and benefits of human germline interventions, focusing especially on the possible threats to the health of future generations. We distinguish between several existing forms of the precautionary principle, assess their plausibility and consider their implications for the ethics of germline modification. We also offer a novel form of the precautionary principle: the sufficientarian precautionary principle. Some plausible versions of the precautionary principle recommend placing somewhat greater weight on avoiding threats to future generations than on achieving short-term benefits. However, no plausible versions of the precautionary principle entail that we should outright reject the use germline gene editing in human reproduction and some, such as the sufficientarian version, might endorse its use.     

Scientific perspectivism: A philosopher of science's response to the challenge of big data biology

Big data biology—bioinformatics, computational biology, systems biology (including ‘omics’), and synthetic biology—raises a number of issues for the philosophy of science. This article deals with several such: Is data-intensive biology a new kind of science, presumably post-reductionistic? To what extent is big data biology data-driven? Can data ‘speak for themselves?’ I discuss these issues by way of a reflection on Carl Woese’s worry that “a society that permits biology to become an engineering discipline, that allows that science to slip into the role of changing the living world without trying to understand it, is a danger to itself.” And I argue that scientific perspectivism, a philosophical stance represented prominently by Giere, Van Fraassen, and Wimsatt, according to which science cannot as a matter of principle transcend our human perspective, provides the best resources currently at our disposal to tackle many of the philosophical issues implied in the modeling of complex, multilevel/multiscale phenomena.     

Improving the science-policy dialogue to meet the challenges of biodiversity conservation: having conversations rather than talking at one-another

A better, more effective dialogue is needed between biodiversity science and policy to underpin the sustainable use and conservation of biodiversity. Many initiatives exist to improve communication, but these largely conform to a ‘linear’ or technocratic model of communication in which scientific “facts” are transmitted directly to policy advisers to “solve problems”. While this model can help start a dialogue, it is, on its own, insufficient, as decision taking is complex, iterative and often selective in the information used. Here, we draw on the literature, interviews and a workshop with individuals working at the interface between biodiversity science and government policy development to present practical recommendations aimed at individuals, teams, organisations and funders. Building on these recommendations, we stress the need to: (a) frame research and policy jointly; (b) promote inter- and trans-disciplinary research and “multi-domain” working groups that include both scientists and policy makers from various fields and sectors; (c) put in place structures and incentive schemes that support interactive dialogue in the long-term. These are changes that are needed in light of continuing loss of biodiversity and its consequences for societal dependence on and benefits from nature.     

Max Weber in the thought of Edward Shils (1910–1995) and Ernest Gellner (1925–1995): the paradox of two Weberian approaches to the understanding of nations and nationalism?

This article traces the paradoxical impact of Weber's oeuvre on two major scholars of nationalism, Ernest Gellner and Edward Shils. Both these scholars died in 1995, leaving behind a rich corpus of writings on the nation and nationalism, much of which was inspired by Max Weber. The paradox is that although neither scholar accepted Weber's sceptical attitude to the concept of ‘nation’, they both used his other major concepts, such as ‘rationality’, ‘disenchantment’, ‘unintended consequences’, the ‘ethic of responsibility’ and ‘charisma’, in their very analyses of the nation and nationalism. And they both saw, each in his own way, the nation and nationalism as constitutive elements of modern societies. However, the paradox ceases being a paradox if one sees the integration, by Shils and Gellner, of concepts of the nation and of nationalism in the analysis of modernity, as a development of Weber's ideas.     

Freedom and Responsibility in Synthetic Genomics: The Synthetic Yeast Project

First introduced in 2011, the Synthetic Yeast Genome (Sc2.0) Project is a large international synthetic genomics project that will culminate in the first eukaryotic cell (Saccharomyces cerevisiae) with a fully synthetic genome. With collaborators from across the globe and from a range of institutions spanning from do-it-yourself biology (DIYbio) to commercial enterprises, it is important that all scientists working on this project are cognizant of the ethical and policy issues associated with this field of research and operate under a common set of principles. In this commentary, we survey the current ethics and regulatory landscape of synthetic biology and present the Sc2.0 Statement of Ethics and Governance to which all members of the project adhere. This statement focuses on four aspects of the Sc2.0 Project: societal benefit, intellectual property, safety, and self-governance. We propose that such project-level agreements are an important, valuable, and flexible model of self-regulation for similar global, large-scale synthetic biology projects in order to maximize the benefits and minimize potential harms.     

Synthetic biology and its alternatives. Descartes,Kant and the idea of engineering biological machines

The engineering-based approach of synthetic biology is characterized by an assumption that ‘engineering by design’ enables the construction of ‘living machines’. These ‘machines’, as biological machines, are expected to display certain properties of life, such as adapting to changing environments and acting in a situated way. This paper proposes that a tension exists between the expectations placed on biological artefacts and the notion of producing such systems by means of engineering; this tension makes it seem implausible that biological systems, especially those with properties characteristic of living beings, can in fact be produced using the specific methods of engineering. We do not claim that engineering techniques have nothing to contribute to the biotechnological construction of biological artefacts. However, drawing on Descartes’s and Kant’s thinking on the relationship between the organism and the machine, we show that it is considerably more plausible to assume that distinctively biological artefacts emerge within a paradigm different from the paradigm of the Cartesian machine that underlies the engineering approach. We close by calling for increased attention to be paid to approaches within molecular biology and chemistry that rest on conceptions different from those of synthetic biology’s engineering paradigm.     

Synthetic conversion of a graded receptor signal into a tunable,reversible switch

The ability to engineer an all‐or‐none cellular response to a given signaling ligand is important in applications ranging from biosensing to tissue engineering. However, synthetic gene network ‘switches’ have been limited in their applicability and tunability due to their reliance on specific components to function. Here, we present a strategy for reversible switch design that instead relies only on a robust, easily constructed network topology with two positive feedback loops and we apply the method to create highly ultrasensitive (n_H>20), bistable cellular responses to a synthetic ligand/receptor complex. Independent modulation of the two feedback strengths enables rational tuning and some decoupling of steady‐state (ultrasensitivity, signal amplitude, switching threshold, and bistability) and kinetic (rates of system activation and deactivation) response properties. Our integrated computational and synthetic biology approach elucidates design rules for building cellular switches with desired properties, which may be of utility in engineering signal‐transduction pathways.     

合成生物学生物安全风险评价与管理

合成生物学(synthetic biology)已迅速发展为生命科学最具发展潜力的分支学科之一,但它同时也会给生态环境和人类健康带来潜在的风险。结合国内外合成生物学发展现状,本文综述了基因回路(DNA-based biocircuits)、最小基因组(minimal genome)、原型细胞(protocells)、化学合成生物学(chemical synthetic biology)等涉及的风险评价、合成生物学与生物安全工程(biosafety engineering)、合成生物学对社会伦理道德法律的影响以及当前热点议题,如生物朋(黑)客(biopunk(or biohackery))、家置生物学(garage biology)、DIY生物学(do-it-yourselfbiology)、生物恐怖主义(bioterrorism)等方面的新进展。分析讨论了世界各国合成生物学以自律监管或技术为主的安全管理原则和基于5个不同政策干预点的5P管理策略的合理性与潜在不足。同时结合我国合成生物学当前研究进展以及现有的安全管理规范,提出了建立以安全评价为核心的法规体系、生物学生物安全规范以及加强研发单位内部管理和生物安全科普宣传等我国合成生物学安全管理制度与措施等建议。     

Impacts of taxonomic inertia for the conservation of African ungulate diversity: an overview

We review the state of African ungulate taxonomy over the last 120 years, with an emphasis on the introduction of the polytypic species concept and the discipline's general neglect since the middle of the 20th century. We single out negative consequences of ‘orthodox’ taxonomy, highlighting numerous cases of neglect of threatened lineages, unsound translocations that led to lineage introgression, and cases of maladaptation to local conditions including parasitic infections. Additionally, several captive breeding programmes have been hampered by chromosome rearrangements caused by involuntary lineage mixing. We advocate that specimen‐based taxonomy should regain its keystone role in mammal research and conservation biology, with its scientific values augmented with genomic evidence. While integration with molecular biology, ecology and behaviour is needed for a full understanding of ungulate alpha diversity, we stress that morphological diversity has been neglected despite its tremendous practical importance for some groups of ‘utilizers’ such as trophy hunters, wildlife tourists and conservationists. We conclude that there is no evidence that purported ‘taxonomic inflation’ has adverse effects on ungulate conservation: rather, it is taxonomic inertia that has such adverse effects. We stress that sound science, founded on robust taxonomy, should underpin effective sustainable management (hunting, ranching, captive breeding and reintroduction programmes) of this unique African natural resource.     

The continuity of microevolution and macroevolution

A persistent debate in evolutionary biology is one over the continuity of microevolution and macroevolution – whether macroevolutionary trends are governed by the principles of microevolution. The opposition of evolutionary trends over different time scales is taken as evidence that selection is uncoupled over these scales. I argue that the paradox inferred by trend opposition is eliminated by a hierarchical application of the ‘geometric‐mean fitness’ principle, a principle that has been invoked only within the limited context of microevolution in response to environmental variance. This principle implies the elimination of well adapted genotypes – even those with the highest arithmetic mean fitness over a shorter time scale. Contingent on premises concerning the temporal structure of environmental variance, selectivity of extinction, and clade‐level heritability, the evolutionary outcome of major environmental change may be viewed as identical in principle to the outcome of minor environmental fluctuations over the short‐term. Trend reversals are thus recognized as a fundamental property of selection operating at any phylogenetic level that occur in response to event severities of any magnitude over all time scales. This ‘bet‐hedging’ perspective differs from others in that a specified, single hierarchical selective process is proposed to explain observed hierarchical patterns of extinction.     

A sufficiency threshold is not a harm principle: A better alternative to best interests for overriding parental decisions

Douglas Diekema influentially argues that interference with parental decisions is not in fact guided by the child’s best interests, but rather by a more permissive standard, which he calls the harm principle. This article first seeks to clarify this alternative position and defend it against certain existing criticisms, before offering a new criticism and alternative. This ‘harm principle’ has been criticized for (i) lack of adequate moral grounding, and (ii) being as indeterminate as the best interest standard that it seeks to replace. I argue that these are not serious problems. I take Diekema’s negative point to be right—our actual standard for intervention is not literally the best interests of the child—but I disagree with his proposed replacement. First, Diekema’s proposed harm threshold should be more carefully distinguished from Mill’s harm principle. Second, there is no reason to assume that the standard for permissible intervention coincides with the threshold for harm (or serious harm). Thus, I propose that the best alternative to the best interests standard is not a harm principle, but rather a sufficiency threshold between adequate (or ‘good enough’) and inadequate (or ‘substandard’) parenting.     

DMS dynamics in the most oligotrophic subtropical zones of the global ocean

The influences of physico-chemical and biological processes on dimethylsulfide (DMS) dynamics in the most oligotrophic subtropical zones of the global ocean were investigated. As metrics for the dynamics of DMS and the so-called ‘summer DMS paradox’ of elevated summer concentrations when surface chlorophyll a (Chl) and particulate organic carbon (POC) levels are lowest, we used the DMS-to-Chl and DMS-to-POC ratios in the context of three independent and complementary approaches. Firstly, field observations of environmental variables (such as the solar radiation dose, phosphorus limitation of phytoplankton and bacterial growth) were used alongside discrete DMS, Chl and POC estimates extracted from global climatologies (i.e., a ‘station based’ approach). We then used monthly climatological data for DMS, Chl, and POC averaged over the biogeographic province wherein a given oligotrophic subtropical zone resides (i.e., a ‘province based’ approach). Finally we employed sensitivity experiments with a new DMS module coupled to the ocean general circulation and biogeochemistry model PISCES to examine the influence of various processes in governing DMS dynamics in oligotrophic regions (i.e., a ‘model based’ approach). We find that the ‘station based’ and ‘province based’ approaches yield markedly different results. Interestingly, the ‘province based’ approach suggests the presence of a ‘summer DMS paradox’ in most all of the oligotrophic regions we studied. In contrast, the ‘station based’ approach suggests that the ‘summer DMS paradox’ is only present in the Sargasso Sea and eastern Mediterranean. Overall, we found the regional differences in the absolute and relative concentrations of DMS between 5 of the most oligotrophic regions of the world’s oceans were better accounted for by their nutrient dynamics (specifically phosphorus limitation) than by physical factors often invoked, e.g., the solar radiation dose. Our ‘model based’ experiments suggest that it is the limitation of phytoplankton/bacterial production and bacterial consumption of DMS by pervasive phosphorus limitation that is responsible for the ‘summer DMS paradox’.     

Synthetic biology: mapping the scientific landscape

This article uses data from Thomson Reuters Web of Science to map and analyse the scientific landscape for synthetic biology. The article draws on recent advances in data visualisation and analytics with the aim of informing upcoming international policy debates on the governance of synthetic biology by the Subsidiary Body on Scientific, Technical and Technological Advice (SBSTTA) of the United Nations Convention on Biological Diversity. We use mapping techniques to identify how synthetic biology can best be understood and the range of institutions, researchers and funding agencies involved. Debates under the Convention are likely to focus on a possible moratorium on the field release of synthetic organisms, cells or genomes. Based on the empirical evidence we propose that guidance could be provided to funding agencies to respect the letter and spirit of the Convention on Biological Diversity in making research investments. Building on the recommendations of the United States Presidential Commission for the Study of Bioethical Issues we demonstrate that it is possible to promote independent and transparent monitoring of developments in synthetic biology using modern information tools. In particular, public and policy understanding and engagement with synthetic biology can be enhanced through the use of online interactive tools. As a step forward in this process we make existing data on the scientific literature on synthetic biology available in an online interactive workbook so that researchers, policy makers and civil society can explore the data and draw conclusions for themselves.     

Environmental protection: applying the precautionary principle and proactive regulation to biotechnology

Biotechnology is a broad field encompassing diverse disciplines from agriculture to zoology. Advances in research are occurring at a rapid pace, and applications that have broad implications socially, economically, ecologically and politically are emerging. Along with notable benefits, environmental consequences that affect core quality-of-life issues for present and future generations are materializing. The precautionary principle should be applied to biotechnology research, activities and products, and a strengthened, enforceable and proactive regulatory framework is needed. The environmental impacts of agriculture, aquaculture, genetically modified organisms (GMOs) and even pharmaceuticals are raising public concerns and demonstrate the need for guidance from a variety of social, economic and scientific disciplines to insure the benefits of biotechnology are enjoyed without unacceptable and irreversible environmental costs.     

Discipline-building in synthetic biology

Despite the multidisciplinary dimension of the kinds of research conducted under the umbrella of synthetic biology, the US-based founders of this new research area adopted a disciplinary profile to shape its institutional identity. In so doing they took inspiration from two already established fields with very different disciplinary patterns. The analogy with synthetic chemistry suggested by the term ‘synthetic biology’ is not the only model. Information technology is clearly another source of inspiration. The purpose of the paper, with its focus on the US context, is to emphasize the diversity of views and agendas coexisting under the disciplinary label synthetic biology, as the two models analysed are only presented as two extreme postures in the community. The paper discusses the question: in which directions the two models shape this emerging field? Do they chart two divergent futures for synthetic biology?     

The way forward in biochar research: targeting trade‐offs between the potential wins

Biochar application to soil is currently widely advocated for a variety of reasons related to sustainability. Typically, soil amelioration with biochar is presented as a multiple‐‘win’ strategy, although it is also associated with potential risks such as environmental contamination. The most often claimed benefits of biochar (i.e. the ‘wins’) include (i) carbon sequestration; (ii) soil fertility enhancement; (iii) biofuel/bioenergy production; (iv) pollutant immobilization; and (v) waste disposal. However, the vast majority of studies ignore possible trade‐offs between them. For example, there is an obvious trade‐off between maximizing biofuel production and maximizing biochar production. Also, relatively little attention has been paid to mechanisms, as opposed to systems impacts, behind observed biochar effects, often leaving open the question as to whether they reflect truly unique properties of biochar as opposed to being simply the short‐term consequences of a fertilization or liming effect. Here, we provide an outline for the future of soil biochar research. We first identify possible trade‐offs between the potential benefits. Second, to be able to better understand and quantify these trade‐offs, we propose guidelines for robust experimental design and selection of appropriate controls that allow both mechanistic and systems assessment of biochar effects and trade‐offs between the wins. Third, we offer a conceptual framework to guide future experiments and suggest guidelines for the standardized reporting of biochar experiments to allow effective between‐site comparisons to quantify trade‐offs. Such a mechanistic and systems framework is required to allow effective comparisons between experiments, across scales and locations, to guide policy and recommendations concerning biochar application to soil.     

Optimal control of population recovery – the role of economic restoration threshold

A variety of ecological systems around the world have been damaged in recent years, either by natural factors such as invasive species, storms and global change or by direct human activities such as overfishing and water pollution. Restoration of these systems to provide ecosystem services entails significant economic benefits. Thus, choosing how and when to restore in an optimal fashion is important, but has not been well studied. Here we examine a general model where population growth can be induced or accelerated by investing in active restoration. We show that the most cost‐effective method to restore an ecosystem dictates investment until the population approaches an ‘economic restoration threshold’, a density above which the ecosystem should be left to recover naturally. Therefore, determining this threshold is a key general approach for guiding efficient restoration management, and we demonstrate how to calculate this threshold for both deterministic and stochastic ecosystems.