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。     

合成生物学技术在材料科学中的应用

材料是人类赖以生存与发展的物质基础,科技和社会的进步都离不开材料技术的发展,未来先进材料的合成和制备必然朝着绿色可持续、低耗高产出、精细可调控、高效多功能的方向发展。以"基因调控·工程设计"为核心的合成生物学技术从分子、细胞层面极大地推动了生命科学的发展,也已经并继续为材料科学的发展注入新的思路和活力。本文将围绕合成生物学技术在材料科学中的应用,以基因回路设计为核心,概念应用为线索,重点介绍合成生物学技术在高分子生物材料和无机纳米材料领域的开发和生产,细胞展示和蛋白定向进化战略对分子材料的筛选和优化,"活体"功能材料、工程菌调节的人工光合系统功能材料体系以及基因回路在材料科学中的应用。     

合成生物学伦理、法律与社会问题探讨

合成生物学是以基因组学、系统生物学知识和分子生物学技术为基础,综合了科学与工程的一门新兴交叉学科。它使生命科学和生物技术研发进入了以人工设计、合成自然界中原本不曾出现的人造生命体系,以及对这些人工体系进行体内、体外优化,或利用这些人造生命体系研究自然生命规律为目标的新时代。然而,合成生物学研究在迅速发展、表现出巨大潜力和应用前景的同时,也引发了社会各界对相关社会、伦理、安全,以及知识产权等问题的重视与讨论。就世界各国针对合成生命对传统意义上生命概念的挑战、合成生物学产品存在的潜在风险危害、合成生物学研究的风险评估与监管等问题进行回顾综述和相关探讨。     

Nanotechnology: convergence with modern biology and medicine

The worldwide emergence of nanoscale science and engineering was marked by the announcement of the National Nanotechnology Initiative (NNI) in January 2000. Recent research on biosystems at the nanoscale has created one of the most dynamic science and technology domains at the confluence of physical sciences, molecular engineering, biology, biotechnology and medicine. This domain includes better understanding of living and thinking systems, revolutionary biotechnology processes, the synthesis of new drugs and their targeted delivery, regenerative medicine, neuromorphic engineering and developing a sustainable environment. Nanobiosystems research is a priority in many countries and its relevance within nanotechnology is expected to increase in the future.     

Tackling the challenges of interdisciplinary bioscience

The ultimate goal for biology is to become a science that formulates our understanding of subcellular, cellular and multicellular systems in terms of quantitative, holistic models that are underpinned by the rigorous principles of the physical sciences and mathematics. This can only be achieved through interdisciplinary research that draws heavily on the expertise and technologies of the physical sciences, engineering, computation and mathematics. Here, I discuss the benefits and challenges (both intellectual and practical) of interdisciplinary bioscience.     

Practising Conservation Biology in a Virtual Rainforest World

The interdisciplinary science of conservation biology provides undergraduate biology students with the opportunity to connect the biological sciences with disciplines including economics, social science and philosophy to address challenging conservation issues. Because of its complexity, students do not often have the opportunity to practise conservation biology. To increase exposure to this science, this paper describes a virtual rainforest island on which students collect data related to forest carbon storage, while also confronting ethical issues. Students are asked to independently make decisions, collect data and explore the island before writing a research report with recommendations for the future management of the island’s forests. The ethics of decision-making are addressed in the students’ research reports and are reinforced through guided class discussion. Students will complete this activity with increased ethical awareness, as well as a better understanding of the challenges associated with the practise of conservation biology.     

A priority paper for the societal and ethical aspects of synthetic biology

As synthetic biology develops into a promising science and engineering field, we need to have clear ideas and priorities regarding its safety, security, ethical and public dialogue implications. Based on an extensive literature search, interviews with scientists, social scientists, a 4 week long public e-forum, and consultation with several stakeholders from science, industry and civil society organisations, we compiled a list of priority topics regarding societal issues of synthetic biology for the years ahead. The points presented here are intended to encourage all stakeholders to engage in the prioritisation of these issues and to participate in a continuous dialogue, with the ultimate goal of providing a basis for a multi-stakeholder governance in synthetic biology. Here we show possible ways to solve the challenges to synthetic biology in the field of safety, security, ethics and the science–public interface.     

合成生物学及其在生物技术中的应用进展

合成生物学是一门21世纪生物学的新兴学科,它着眼生物科学与工程科学的结合,把生物系统当作工程系统"从下往上"进行处理,由"单元"(unit)到"部件"(device)再到"系统"(system)来设计,修改和组装细胞构件及生物系统.合成生物学是分子和细胞生物学、进化系统学、生物化学、信息学、数学、计算机和工程等多学科交叉的产物.目前研究应用包括两个主要方面:一是通过对现有的、天然存在的生物系统进行重新设计和改造,修改已存在的生物系统,使该系统增添新的功能.二是通过设计和构建新的生物零件、组件和系统,创造自然界中尚不存在的人工生命系统.合成生物学作为一门建立在基因组方法之上的学科,主要强调对创造人工生命形态的计算生物学与实验生物学的协同整合.必须强调的是,用来构建生命系统新结构、产生新功能所使用的组件单元既可以是基因、核酸等生物组件,也可以是化学的、机械的和物理的元件.本文跟踪合成生物学研究及应用,对其在DNA水平编程、分子修饰、代谢途径、调控网络和工业生物技术等方面的进展进行综述.     

The art of trans-boundary governance: the case of synthetic biology

Synthetic biology raises few, if any, social concerns that are distinctively new. Similar to many other convergent technologies, synthetic biology’s interface across various scientific communities and interests groups presents an incessant challenge to political and conceptual boundaries. However, the scale and intensity of these interfaces seem to necessitate a reflection over how corresponding governance capacities can be developed. This paper argues that, in addition to existing regulatory approaches, such capacities may be gained through the art of trans-boundary governance, which is not only attentive to the crossing and erosion of particular boundaries but also adept in keeping up with the dynamics among evolving networks of actors.     

Grand challenges in organismal biology

A renaissance in organismal biology has been sparked by recent conceptual, theoretical, methodological, and computational advances in the life sciences, along with an unprecedented interdisciplinary integration with Mathematics, Engineering, and the physical sciences. Despite a decades-long trend toward reductionist approaches to biological problems, it is increasingly recognized that whole organisms play a central role in organizing and interpreting information from across the biological spectrum. Organisms represent the nexus where sub- and supra-organismal processes meet, and it is the performance of organisms within the environment that provides the material for natural selection. Here, we identify five "grand challenges" for future research in organismal biology. It is intended that these challenges will spark further discussion in the broader community and identify future research priorities, opportunities, and directions, which will ultimately help to guide the allocation of support for and training in organismal biology.     

Authentic teaching and learning through synthetic biology

Synthetic biology is an emerging engineering discipline that, if successful, will allow well-characterized biological components to be predictably and reliably built into robust organisms that achieve specific functions. Fledgling efforts to design and implement a synthetic biology curriculum for undergraduate students have shown that the co-development of this emerging discipline and its future practitioners does not undermine learning. Rather it can serve as the lynchpin of a synthetic biology curriculum. Here I describe educational goals uniquely served by synthetic biology teaching, detail ongoing curricula development efforts at MIT, and specify particular aspects of the emerging field that must develop rapidly in order to best train the next generation of synthetic biologists.     

哺乳动物合成生物学在生物医学领域的研究进展

虽然合成生物学还处于早期研究阶段,但最近十年,该领域取得了非常显著的研究进展。合成生物学是以工程学思想为基础,通过人工设计、改造基因线路,从而赋予细胞或生物体新的功能,现已广泛应用于各个领域。随着人们对基因线路设计的深入研究,使得合成生物学研究走向临床应用成为可能。本文将围绕哺乳动物合成生物学在疾病治疗方面的研究进展,介绍基因线路的设计思路和方法、不同诱导因子调控的开环式基因线路以及用于疾病诊疗的闭环式基因环路在生物医学领域的应用。最后对合成生物学走向临床治疗的应用前景和挑战进行展望。     

合成生物学技术在环境保护中的应用

合成生物学是一个基于生物学和工程学原理的科学领域,其目的是重新设计和重组微生物,以优化或创建具有增强功能的新生物系统。该领域利用分子工具、系统生物学和遗传框架的重编程,从而构建合成途径以获得具有替代功能的微生物。传统上,合成生物学方法通常旨在开发具有成本效益的微生物细胞工厂进而从可再生资源中生产化学物质。然而,近年来合成生物学技术开始在环境保护中发挥着更直接的作用。本综述介绍了基因工程中的合成生物学工具,讨论了基于基因工程的微生物修复策略,强调了合成生物学技术可以通过响应特定污染物进行生物修复来保护环境。其中,规律间隔成簇短回文重复序列(Clustered Regularly Interspersed Short Palindromic Repeats, CRISPR)技术在基因工程细菌和古细菌的生物修复中得到了广泛应用,生物修复领域也出现了很多新的先进技术,包括生物膜工程、人工微生物群落的构建、基因驱动、酶和蛋白质工程等。有了这些新的技术和工具,生物修复将成为当今最好和最有效的污染物去除方式之一。     

合成功能菌群的构建及其工程化应用

自然界中存在着大量的天然微生物群落,不同种群的微生物通过通信及分工拓展了单菌的性能边界,降低了整体的代谢负担并增加了对环境的适应性。合成生物学依据工程设计原理构建或改造基本功能元件、基因线路和底盘细胞,从而对生命的运行过程进行具有目的性的重新编程,获得丰富及可控的生物学功能。将这种工程设计的原理引入菌群,获得结构明确及功能可调的合成群落,可以为合成功能菌群的理论研究到应用提供思路及方法。本文回顾了近年来合成功能菌群领域的相关工作,对合成功能菌群的设计原则、构建方法以及应用进行详细介绍,并对未来的发展进行了展望。     

Enabling tools for tissue engineering

Tissue engineering is a multidisciplinary field that combines engineering, physical sciences, biology, and medicine to restore or replace tissues and organs functions. In this review, enabling tools for tissue engineering are discussed in the context of four key areas or pillars: prediction, production, performance, and preservation. Prediction refers to the computational modeling where the ability to simulate cellular behavior in complex three-dimensional environments will be essential for design of tissues. Production refer imaging modalities that allow high resolution, non-invasive monitoring of the development and incorporation of tissue engineered constructs. Lastly, preservation includes biochemical tools that permit cryopreservation, vitrification, and freeze-drying of cells and tissues. Recent progress and future perspectives for development in each of these key areas are presented.     

《生物多样性公约》框架下合成生物学 谈判新进展及我国对策

合成生物学技术和产品因其广阔的应用前景和难以预知的生态风险, 受到各国的广泛关注。2014年10月在韩国平昌召开的《生物多样性公约》第十二次缔约方大会上, 合成生物学首次被作为正式议题进行讨论。本文梳理了《生物多样性公约》框架下合成生物学从提出到成为“新的与正在出现的议题”的过程, 分析了《生物多样性公约》在该议题上对缔约国的最新要求, 以及我国合成生物学技术发展和风险评估现状。当前我国合成生物学研究处于起步阶段,近年来的科研投入不断增大,但距离成熟的商业化仍有相当距离。我国对相关技术风险评估能力欠缺,且尚未明确负责其生物安全管理的主管部门。本文提出了以严控风险、适度鼓励研究开发和要求发达国家提供更多技术支持的谈判对策, 以及明确合成生物学安全风险管理的政府主管部门、通过技术开发以推动风险评估、构建国家合成生物学数据库和建立专业风险评估团队等履约建议。     

Aiming high,but investing little

The French government has ambitious goals to make France a leading nation for synthetic biology research, but it still needs to put its money where its mouth is and provide the field with dedicated funding and other support.Synthetic biology is one of the most rapidly growing fields in the biological sciences and is attracting an increasing amount of public and private funding. France has also seen a slow but steady development of this field: the establishment of a national network of synthetic biologists in 2005, the first participation of a French team at the International Genetically Engineered Machine competition in 2007, the creation of a Master''s curriculum, an institute dedicated to synthetic and systems biology at the University of Évry-Val-d''Essonne-CNRS-Genopole in 2009–2010, and an increasing number of conferences and debates. However, scientists have driven the field with little dedicated financial support from the government.Yet the French government has a strong self-perception of its strengths and has set ambitious goals for synthetic biology. The public are told about a “new generation of products, industries and markets” that will derive from synthetic biology, and that research in the field will result in “a substantial jump for biotechnology” and an “industrial revolution”[1,2]. Indeed, France wants to compete with the USA, the UK, Germany and the rest of Europe and aims “for a world position of second or third”[1]. However, in contrast with the activities of its competitors, the French government has no specific scheme for funding or otherwise supporting synthetic biology[3]. Although we read that “France disposes of strong competences” and “all the assets needed”[2], one wonders how France will achieve its ambitious goals without dedicated budgets or detailed roadmaps to set up such institutions.In fact, France has been a straggler: whereas the UK and the USA have published several reports on synthetic biology since 2007, and have set up dedicated governing networks and research institutions, the governance of synthetic biology in France has only recently become an official matter. The National Research and Innovation Strategy (SNRI) only defined synthetic biology as a “priority” challenge in 2009 and created a working group in 2010 to assess the field''s developments, potentialities and challenges; the report was published in 2011[1].At the same time, the French Parliamentary Office for the Evaluation of Scientific and Technological Choices (OPECST) began a review of the field “to establish a worldwide state of the art and the position of our country in terms of training, research and technology transfer”. Its 2012 report entitled The Challenges of Synthetic Biology[2] assessed the main ethical, legal, economic and social challenges of the field. It made several recommendations for a “controlled” and “transparent” development of synthetic biology. This is not a surprise given that the development of genetically modified organisms and nuclear power in France has been heavily criticized for lack of transparency, and that the government prefers to avoid similar future controversies. Indeed, the French government seems more cautious today: making efforts to assess potential dangers and public opinion before actually supporting the science itself.Both reports stress the necessity of a “real” and “transparent” dialogue between science and society and call for “serene […] peaceful and constructive” public discussion. The proposed strategy has three aims: to establish an observatory, to create a permanent forum for discussion and to broaden the debate to include citizens[4]. An Observatory for Synthetic Biology was set up in January 2012 to collect information, mobilize actors, follow debates, analyse the various positions and organize a public forum. Let us hope that this observatory—unlike so many other structures—will have a tangible and durable influence on policy-making, public opinion and scientific practice.Many structural and organizational challenges persist, as neither the National Agency for Research nor the National Centre for Scientific Research have defined the field as a funding priority and public–private partnerships are rare in France. Moreover, strict boundaries between academic disciplines impede interdisciplinary work, and synthetic biology is often included in larger research programmes rather than supported as a research field in itself. Although both the SNRI and the OPECST reports make recommendations for future developments—including setting up funding policies and platforms—it is not clear whether these will materialize, or when, where and what size of investments will be made.France has ambitious goals for synthetic biology, but it remains to be seen whether the government is willing to put ‘meat to the bones'' in terms of financial and institutional support. If not, these goals might come to be seen as unrealistic and downgraded or they will be replaced with another vision that sees synthetic biology as something that only needs discussion and deliberation but no further investment. One thing is already certain: the future development of synthetic biology in France is a political issue.     

Spatial memory and animal movement

Memory is critical to understanding animal movement but has proven challenging to study. Advances in animal tracking technology, theoretical movement models and cognitive sciences have facilitated research in each of these fields, but also created a need for synthetic examination of the linkages between memory and animal movement. Here, we draw together research from several disciplines to understand the relationship between animal memory and movement processes. First, we frame the problem in terms of the characteristics, costs and benefits of memory as outlined in psychology and neuroscience. Next, we provide an overview of the theories and conceptual frameworks that have emerged from behavioural ecology and animal cognition. Third, we turn to movement ecology and summarise recent, rapid developments in the types and quantities of available movement data, and in the statistical measures applicable to such data. Fourth, we discuss the advantages and interrelationships of diverse modelling approaches that have been used to explore the memory–movement interface. Finally, we outline key research challenges for the memory and movement communities, focusing on data needs and mathematical and computational challenges. We conclude with a roadmap for future work in this area, outlining axes along which focused research should yield rapid progress.     

Designing de novo: interdisciplinary debates in synthetic biology

Synthetic biology is often presented as a promissory field that ambitions to produce novelty by design. The ultimate promise is the production of living systems that will perform new and desired functions in predictable ways. Nevertheless, realizing promises of novelty has not proven to be a straightforward endeavour. This paper provides an overview of, and explores the existing debates on, the possibility of designing living systems de novo as they appear in interdisciplinary talks between engineering and biological views within the field of synthetic biology. To broaden such interdisciplinary debates, we include the views from the social sciences and the humanities and we point to some fundamental sources of disagreement within the field. Different views co-exist, sometimes as controversial tensions, but sometimes also pointing to integration in the form of intermediate positions. As the field is emerging, multiple choices are possible. They will inform alternative trajectories in synthetic biology and will certainly shape its future. What direction is best is to be decided in reflexive and socially robust ways.     

Community outreach as an iterative dialogue among scientists and communities in the Texas gulf coast region

In response to significant environmental health challenges in Southeast Texas, a National Institute for Environmental Health Sciences Center at the University of Texas Medical Branch at Galveston was created to promote and conduct inter-disciplinary research in the areas of: (1) the molecular biology of DNA repair, replication and mutagenesis, (2) asthma pathogenesis in response to oxidative stress and viral exposures, and (3) environmental toxicant biotransformation. In addition, the NIEHS Center maintains close ties with neighboring communities through an active Community Outreach & Education Program (COEP) that develops and disseminates translational materials for use in environmental health awareness outreach, toxicology consultation, K-12 curriculum enrichment and in developing site-specific Community Partnership projects. The COEP core service divisions include: Environmental Arts & Sciences, Asthma Outreach & Education, Theater Outreach & Education, and Public Forum & Toxics Assistance. Public Forums focus on the use of Augusto Boal's Forum Theater dramaturgy to include the voices and local knowledge of communities within the process of Participatory Research. Forums create the preconditions for significant partnerships that link the hazardous risk perceptions and environmental health needs of communities with the expertise of NIEHS Center investigators and translational services provided through COEP outreach programs. The Forum process also creates leadership cores within environmentally challenged communities that facilitate the ongoing translational process and maintain the vital linkage between the health needs of communities and the analytic tools and the field and clinical technologies of the environmental sciences.