Development of community of practice to support quantitative risk assessment for synthetic biology products: contaminant bioremediation and invasive carp control as cases

Synthetic biology has the potential for a broad array of applications. However, realization of this potential is challenged by the paucity of relevant data for conventional risk assessment protocols, a limitation due to to the relative nascence of the field, as well as the poorly characterized and prioritized hazard, exposure, and dose–response considerations associated with the development and use of synthetic biology-derived organisms. Where quantitative risk assessment approaches are necessarily to fulfill regulatory requirements for review of products containing genetically modified organisms, this paper reviews one potential avenue for early-stage quantitative risk assessment for biosafety considerations of synthetic biology organism deployment into the environment. Building from discussion from a March 2018 US Army Engineer Research and Development Center workshop on developing such quantitative risk assessment for synthetic biology, this paper reviews the findings and discussion of workshop participants. This paper concludes that, while synthetic biology risk assessment and governance will continue to refine and develop in the coming years, a quantitative framework that builds from existing practice is one potentially beneficial option for risk assessors that must contend with the technology’s limited hazard characterization or exposure assessment considerations in the near term.     

Regulatory aspects

Summary At this time, there is no US legislation that is specifically aimed at regulating the environmental release of genetically engineered organisms or their modified components, either during the research and development stage or during application. There are some statutes, administered by several federal agencies, whose language is broad enough to allow the extension of intended coverage to include certain aspects of biotechnology. The one possible exception is FIFRA, which has already brought about the registration of several natural microbial pesticides but which also has provision for requiring the registration of strain improved microbial pesticides. Nevertheless, there may be gaps in coverage even if all pertinent statutes were to be actively applied to the control of environmental release of genetically modified substances. The decision to regulate biotechnology under TSCA was justified, in part, on the basis of its intended role as a gap-filling piece of environmental legislation. The advantage of regulating biotechnology under TSCA is that this statute, unlike others, is concerned with all media of exposure (air, water, soil, sediment, biota) that may pose health and environmental hazards. Experience may show that extending existing legislation to regulate biotechnology is a poor compromise compared to the promulgation of new legislation specifically designed for this purpose. It appears that many other countries are ultimately going to take the latter course to regulate biotechnology.     

ECOLOGICAL CONSEQUENCE ASSESSMENT: EFFECTS OF BIOENGINEERED ORGANISMS1

ABSTRACT: The introduction of genetically altered microorganisms into natural ecosystems presents fundamentally new problems in risk assessment and ecological effect evaluation. Novel microorganisms, produced by any of several new methods, have the ability to survive and reproduce in the environment. Since most of these organisms are bacteria, they have the potential to interfere with natural processes, displace natural populations, infect new hosts, move between ecosystems, and cause far-reaching ecological disturbanes. This paper reviews currently available methods in ecological research that might be used in evaluating the ecological effects of releasing genetically altered microorganisms. Both structural and functional evaluations are critically reviewed. Microcosm, mesocosm, and field tests should provide valuable predictions concerning the potential ecological impact of genetically altered organisms. Ecosystem assessments will also be useful in post-release studies such as those currently used to evaluate toxic impacts. The present problem does not require the development of new testing methods but rather the creation of adequate predictive models (both conceptual and systems-based) to predict the potential for adverse effect of genetically altered organisms.     

Ecological risk assessment of TBT in Ise Bay

An ecological risk assessment of tributyltin (TBT) in Ise Bay was conducted using the margin of exposure (MOE) method. The assessment endpoint was defined to protect the survival, growth and reproduction of marine organisms. Sources of TBT in this study were assumed to be commercial vessels in harbors and navigation routes. Concentrations of TBT in Ise Bay were estimated using a three-dimensional hydrodynamic model, an ecosystem model and a chemical fate model. Estimated MOEs for marine organisms for 1990 and 2008 were approximately 0.1-2.0 and over 100 respectively, indicating a declining temporal trend in the probability of adverse effects. The chemical fate model predicts a much longer persistence of TBT in sediments than in the water column. Therefore, it is necessary to monitor the harmful effects of TBT on benthic organisms.     

Regulatory Oversight of Genetically Engineered Microorganisms: Has Regulation Inhibited Innovation?

/ Using detailed interviews with company representatives and researchers in the field, this paper examines the factors that might account for the slow pace of development of genetically engineered microorganisms (GEMs) intended for environmental release. We specifically analyzed the role of the regulatory system in shaping innovation. We identified at least two cases where industry decided to discontinue the development of a genetically engineered microbial product because of concerns over regulatory oversight. However, most often industry decisions to continue or halt development of GEMs were based on an evaluation of the particular product's efficacy and potential for profitability. Thus the inability of GEMs to perform up to expectations in the field, rather than the regulatory constraints, appears to be the factor responsible for the slow pace of development. KEY WORDS: Genetically engineered microorganisms; Biotechnology; Regulation of biotechnology; Innovation; Environmental release     

Including Public Perspectives in Industrial Biotechnology and the Biobased Economy

Industrial (“white”) biotechnology promises to contribute to a more sustainable future. Compared to current production processes, cases have been identified where industrial biotechnology can decrease the amount of energy and raw materials used to make products and also reduce the amount of emissions and waste produced during production. However, switching from products based on chemical production processes and fossil fuels towards “biobased” products is at present not necessarily economically viable. This is especially true for bulk products, for example ethanol production from biomass. Therefore, scientists are also turning to genetic modification as a means to develop organisms that can produce at lower costs. These include not only micro-organisms, but also organisms used in agriculture for food and feed.The use of genetic modification for “deliberate release” purposes, in particular, has met great opposition in Europe. Many industrial biotechnology applications may, due to their scale, entail deliberate releases of GM organisms. Thus, the biobased economy brings back a familiar question; is it ethically justifiable, and acceptable to citizens, to expose the environment and society to the risks associated with GM, in order to protect that same environment and to sustain our affluent way of life? For a successful innovation towards a biobased economy, its proponents, especially producers, need to take into account (take responsibility for) such issues when developing new products and processes. These issues, and how scientists can interact with citizens about them in a timely way, are further explored in projects at Delft University and Leiden University, also in collaboration with Utrecht University.     

Genetically Engineered Animals,Drugs, and Neoliberalism: The Need for a New Biotechnology Regulatory Policy Framework

Genetically engineered (GE) animals that are meant for release in the wild could significantly impact ecosystems given the interwoven or entangled existence of species. Therefore, among other things, it is all too important that regulatory agencies conduct entity appropriate, rigorous risk assessments that can be used for informed decision-making at the local, national and global levels about the release of those animals in the wild. In the United States (US), certain GE animals that are intended for release in the wild may be regulated as new animal drugs by the Food and Drug Administration. This paper argues that the decision to treat them as new animal drugs is attributable to the influence of neoliberalism on the US biotechnology regulatory policy framework. The case is made that there should be public democratic deliberations and decision-making about the values and concerns that should guide the nation’s biotechnology regulatory policy paradigm, including the risk assessment process for GE animals meant for release in the wild.     

The Magic Bullet Criticism of Agricultural Biotechnology

One common method of criticizing genetically modified organisms (GMOs) is to label them as “magic bullets.” However, this criticism, like many in the debate over GMOs, is not very clear. What exactly is the “magic bullet criticism”? What are its origins? What flaw is it pointing out in GM crops and agricultural biotechnology? What is the scope of the criticism? Does it apply to all GMOs, or just some? Does it point to a fatal flaw, or something that can be fixed? The goal of this paper is to answer these questions and clarify the magic bullet criticism of agricultural biotechnology. It is hoped that the results of this exercise will be helpful in advancing deliberation over the role GMOs and agricultural biotechnology should play in 21st century agriculture.     

Environmental occurrences, behavior, fate, and ecological effects of nanomaterials: an introduction to the special series

The release of engineered nanomaterials (ENMs) into the biosphere will increase as industries find new and useful ways to utilize these materials. Scientists and engineers are beginning to assess the material properties that determine the fate, transport, and effects of ENMs; however, the potential impacts of released ENMs on organisms, ecosystems, and human health remain largely unknown. This special collection of four review papers and four technical papers identifies many key and emerging knowledge gaps regarding the interactions between nanomaterials and ecosystems. These critical knowledge gaps include the form, route, and mass of nanomaterials entering the environment; the transformations and ultimate fate of nanomaterials in the environment; the transport, distribution, and bioavailability of nanomaterials in environmental media; and the organismal responses to nanomaterial exposure and effects of nanomaterial inputs, on ecological communities and biogeochemical processes at relevant environmental concentrations and forms. This introductory section summarizes the state of knowledge and emerging areas of research needs identified within the special collection. Despite recent progress in understanding the transport, transformations, and fate of ENMs in model environments and organisms, there remains a large need for fundamental information regarding releases, distribution, transformations and persistence, and bioavailability of nanomaterials. Moreover, fate, transport, bioaccumulation, and ecological impacts research is needed using environmentally relevant concentrations and forms of ENMs in real field materials and with a broader range of organisms.     

Exploiting Abstract Possibilities: A Critique of the Concept and Practice of Product Patenting

Developments in biotechnology and genomics have moved the issue of patenting scientific and technological inventions toward the center of interest. In particular, the patentability of genes of plants, animals, or humans and of genetically modified (parts of) living organisms has been discussed, and questioned, from various normative perspectives. This paper aims to contribute to this debate. For this purpose, it first explains a number of relevant aspects of the theory and practice of patenting. The focus is on a special and increasingly significant type of patents, namely product patents. The paper provides three general arguments against the concept and practice of product patenting. The first argument briefly considers the claim that patents are legitimate because they promote socially useful innovation. Against this claim, it is argued that product patents may hamper rather than promote such innovation. The second and main argument concludes that product patents are not adequately based on actual technological inventions, as they should be according to the usual criteria of patentability. The principal moral issue is that product patents tend to reward patentees for inventions they have not really made available. The final argument proposes a method for patenting the heat of the sun. Assuming that granting this patent will be generally considered absurd, the argument exposes a further, fundamental problem of the concept and practice of product patenting.     

Ethics in the Societal Debate on Genetically Modified Organisms: A (Re)Quest for Sense and Sensibility

Via a historical reconstruction, this paper primarily demonstrates how the societal debate on genetically modified organisms (GMOs) gradually extended in terms of actors involved and concerns reflected. It is argued that the implementation of recombinant DNA technology out of the laboratory and into civil society entailed a “complex of concerns.” In this complex, distinctions between environmental, agricultural, socio-economic, and ethical issues proved to be blurred. This fueled the confusion between the wider debate on genetic modification and the risk assessment of transgenic crops in the European Union. In this paper, the lasting skeptical and/or ambivalent attitude of Europeans towards agro-food biotechnology is interpreted as signaling an ongoing social request – and even a quest – for an evaluation of biotechnology with Sense and Sensibility. In this (re)quest, a broader-than-scientific dimension is sought for that allows addressing the GMO debate in a more “sensible” way, whilst making “sense” of the different stances taken in it. Here, the restyling of the European regulatory frame on transgenic agro-food products and of science communication models are discussed and taken to be indicative of the (re)quest to move from a merely scientific evaluation and risk-based policy towards a socially more robust evaluation that takes the “non-scientific” concerns at stake in the GMO debate seriously.     

Fate and transport of engineered nanomaterials in the environment

With the fast development of nanotechnology, engineered nanomaterials (ENMs) will inevitably be introduced into the various environment. Increasing studies showed the toxiccity of various ENMs, which raises concerns over their fate and transport in the environment. This review focuses on advances in the research on environmental transport and fate of ENMs. Aggregation and suspension behaviors of ENMs determining their fate and transport in aqueous environment are discussed, with emphasis on the influencing factors, including natural colloids, natural organic matter, pH, and ionic strength. Studies on the transport of ENMs in porous media and its influencing factors are reviewed, and transformation and organismcleansing, as two fate routes of ENMs in the environment, are addressed. Future research directions and outlook in the environmental transport and fate of ENMs are also presented.     

Sustainable Use of Biotechnology for Bioenergy Feedstocks

Done correctly, cellulosic bioenergy should be both environmentally and economically beneficial. Carbon sequestration and decreased fossil fuel use are both worthy goals in developing next-generation biofuels. We believe that biotechnology will be needed to significantly improve yield and digestibility of dedicated perennial herbaceous biomass feedstocks, such as switchgrass and Miscanthus, which are native to the US and China, respectively. This Forum discusses the sustainability of herbaceous feedstocks relative to the regulation of biotechnology with regards to likely genetically engineered traits. The Forum focuses on two prominent countries wishing to develop their bioeconomies: the US and China. These two countries also share a political desire and regulatory frameworks to enable the commercialization and wide release of transgenic feedstocks with appropriate and safe new genetics. In recent years, regulators in both countries perform regular inspections of transgenic field releases and seriously consider compliance issues, even though the US framework is considered to be more mature and stringent. Transgene flow continues to be a pertinent environmental and regulatory issue with regards to transgenic plants. This concern is largely driven by consumer issues and ecological uncertainties. Regulators are concerned about large-scale releases of transgenic crops that have sexually compatible crops or wild relatives that can stably harbor transgenes via hybridization and introgression. Therefore, prior to the commercialization or extensive field testing of transgenic bioenergy feedstocks, we recommend that mechanisms that ensure biocontainment of transgenes be instituted, especially for perennial grasses. A cautionary case study will be presented in which a plant’s biology and ecology conspired against regulatory constraints in a non-biomass crop perennial grass (creeping bentgrass, Agrostis stolonifera), in which biocontainment was not attained. Appropriate technologies that could be applied to perennial grass feedstocks for biocontainment are discussed.     

Biotechnology and naturalness in the genomics era: plotting a timetable for the biotechnology debate

Debates on the role of biotechnology in food production are beset with notorious ambiguities. This already applies to the term “biotechnology” itself. Does it refer to the use and modification of living organisms in general, or rather to a specific set of technologies developed quite recently in the form of bioengineering and genetic modification? No less ambiguous are discussions concerning the question to what extent biotechnology must be regarded as “unnatural.” In this article it will be argued that, in order to disentangle some of the ambiguities involved, we have to broaden the temporal horizon of the debate. Ideas about biotechniques and naturalness have evolved in various socio-historical contexts and their historical origins will determine to a considerable extent their actual meaning and use in contemporary deliberations. For this purpose, a comprehensive timetable is developed, beginning with the Neolithic revolution ~10,000 years ago (resulting in the emergence of agriculture and the Common Human Pattern) up to the biotech revolution as it has evolved from the 1970s onwards—sometimes referred to as a second “Genesis.” The concept of nature that emerged in the context of the “Common Human Pattern” differs considerably from traditional philosophical concepts of nature (such as coined by Aristotle), as well as from the scientific view of nature conveyed by the contemporary life sciences. A clarification of these different historical backdrops will allow us to understand and elucidate the conceptual ambiguities that are at work in contemporary debates on biotechnology and the place of human beings in nature.     

Science and values in risk assessment: The case of deliberate release of genetically engineered organisms

To make more responsible decisions regarding risk and to understand disagreements and controversies in risk assessments, it is important to know how and where values are infused into risk assessment and how they are embedded in the conclusions. In this article an attempt is made to disentangle the relationship of science and values in decision-making concerning the deliberate release of genetically modified organisms (GMOs) into the environment. This exercise in applied philosophy of science is based on Helen Longino's contextual empiricism which attempts to reconcile the objectivity of science with its social and cultural construction. Longino distinguishes different levels of research on which values apparently contextual with respect to a given research program can shape the knowledge emerging from that program. Her scheme is applied for locating and identifying the values that affect environment risk assessments of the field experiments with GMOs. The article concludes with some provisional suggestions for the decision process and the role of scientists in it.     

Fate and movement of microorganisms in the environment

Summary This literature review indicates how little is known about the growth of introduced bacteria. The available data base is so sparse that one can only speculate on the environmental conditions and the physiological traits that are needed to permit bacterial growth. Although methods are available to label organisms so that their multiplication can be detected under natural conditions, those methods have not been used sufficiently often to provide a meaningful base of information to allow a definition of conditions that favor multiplication of particular species or the organisms that are likely to proliferate in particular environments. However, because methods exist to monitor microbial growth, and new and better methods can be developed easily, it should not be difficult—provided research funds are made available—to expand greatly the data base and provide adequate information to be used for predicting the behavior of genetically engineered organisms in nature.     

Applications

Summary Economic incentives have spurred numerous applications of genetically engineered organisms in manufacture of pharmaceuticals and industrial chemicals. These successes, involving a variety of methods of genetic manipulation, have dispelled early fears that genetic engineering could not be handled safely, even in the laboratory. Consequently, the potential for applications in the wider environment without physical containment is being considered for agriculture, mining, pollution control, and pest control. These proposed applications range from modest extensions of current plant breeding techniques for new disease-resistant species to radical combinations of organisms (for example, nitrogen-fixing corn plants). These applications raise concerns about potential ecological impacts (see chapter 5), largely because of adverse experiences with both deliberate and inadvertent introductions of nonindigenous species.     

Managing the potential public health risks from bioaerosol liberation at commercial composting sites in the UK: An analysis of the evidence base

The diversion of biodegradable waste from landfill is of key importance in developing a sustainable waste strategy for the next decade and beyond. The proliferation of waste treatment technologies such as Mechanical Biological Treatment, Anaerobic Digestion and Composting will be paramount in achieving this strategic goal. This paper evaluates the scientific information needed to undertake an effective assessment of the potential public health risks from exposure to bioaerosols in the vicinity of commercial composting activities. Knowledge gaps currently exist in the scientific and regulatory community that limit our ability to effectively characterise source-term emissions, develop reliable dose–response data and accurately model the dispersion of bioaerosols. Consequently reliable risk estimates cannot be developed to inform the management of these potential risks. This uncertainty may prove a barrier to progress in achieving waste diversion and composting targets in Wales and the rest of the UK. A robust and extensive evidence base is required to inform the risk assessment process. This paper advocates the need for further, more focussed research into hazard characterisation of viable and non-viable organisms, improved dose–response data, exposure assessment techniques and an evaluation of the existing risk control and mitigation measures currently adopted. It is hoped that his will enable effective, timely and proportional risk management and mitigation measures to be developed that will foster the confidence required in composting technologies to achieve waste diversion targets and develop sustainable waste strategies.     

Between Precautionary Principle and “Sound Science”: Distributing the Burdens of Proof

Opponents of biotechnology ofteninvoke the Precautionary Principle to advancetheir cause, whereas biotech enthusiasts preferto appeal to ``sound science.' Publicauthorities are still groping for a usefuldefinition. A crucial issue in this debate isthe distribution of the burden of proof amongthe parties favoring and opposing certaintechnological developments. Indeed, the debateon the significance and scope of thePrecautionary Principle can be fruitfullyre-framed as a debate on the proper division ofburdens of proof. In this article, we attemptto arrive at a more refined way of thinkingabout this problem in order to escape from theexisting polarization of views between ``guiltyuntil proven innocent' and ``innocent untilproven guilty.' This way of thinking alsoenables a critical review of currentdemarcations between risk assessment and riskmanagement, or science and politics, and of themorally laden controversy on the relativeimportance of type-I and type-II errors instatistical testing.