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.     

Synthetic therapeutic gene circuits in mammalian cells

In the emerging field of synthetic biology, scientists are focusing on designing and creating functional devices, systems, and organisms with novel functions by engineering and assembling standardised biological building blocks. The progress of synthetic biology has significantly advanced the design of functional gene networks that can reprogram metabolic activities in mammalian cells and provide new therapeutic opportunities for future gene- and cell-based therapies. In this review, we describe the most recent advances in synthetic mammalian gene networks designed for biomedical applications, including how these synthetic therapeutic gene circuits can be assembled to control signalling networks and applied to treat metabolic disorders, cancer, and immune diseases. We conclude by discussing the various challenges and future prospects of using synthetic mammalian gene networks for disease therapy.     

Parts plus pipes: synthetic biology approaches to metabolic engineering

Synthetic biologists combine modular biological "parts" to create higher-order devices. Metabolic engineers construct biological "pipes" by optimizing the microbial conversion of basic substrates to desired compounds. Many scientists work at the intersection of these two philosophies, employing synthetic devices to enhance metabolic engineering efforts. These integrated approaches promise to do more than simply improve product yields; they can expand the array of products that are tractable to produce biologically. In this review, we explore the application of synthetic biology techniques to next-generation metabolic engineering challenges, as well as the emerging engineering principles for biological design.     

非常规酵母的分子遗传学及合成生物学研究进展

先进的合成生物学技术与传统的分子遗传学技术的结合更有助于实现酵母底盘细胞的快速改造和优化。酵母合成生物学研究最早开始于常规酵母——酿酒酵母(Saccharomyces cerevisiae),近些年来又迅速扩展至一些非常规酵母,包括巴斯德毕赤酵母(Pichiapastoris)、解脂耶氏酵母(Yarrowialipolytica)、乳酸克鲁维酵母(Kluyveromyces lactis)和多形汉逊酵母(Hansenula polymorpha)等。借助合成生物学技术与工具,目前科学家们已经成功开发出了能够高效生产生物材料、生物燃料、生物基化学品、蛋白质制剂、食品添加剂和药物等工业产品的重组非常规酵母工程菌株。本文系统总结了合成生物学工具(主要是基因组编辑工具)、合成生物学组件(主要是启动子和终止子)和相关分子遗传学方法在上述非常规酵母系统(底盘细胞)中的最新研究进展和应用情况,并讨论了其他合成生物学技术在这些非常规酵母表达系统中的潜在适用性和应用前景。这为研究人员利用合成生物学方法在这一新型非模式微生物底盘细胞中设计和构建各种高附加值工业产品的异源合成模块并最终实现目标化合物的高效生物合成提供了科学的理论指导。     

Synthetic biology in biofilms: Tools,challenges, and opportunities

The field of synthetic biology seeks to program living cells to perform novel functions with applications ranging from environmental biosensing to smart cell-based therapeutics. Bacteria are an especially attractive chassis organism due to their rapid growth, ease of genetic manipulation, and ability to persist across many environmental niches. Despite significant progress in bacterial synthetic biology, programming bacteria to perform novel functions outside the well-controlled laboratory context remains challenging. In contrast to planktonic laboratory growth, bacteria in nature predominately reside in the context of densely packed communities known as biofilms. While biofilms have historically been considered environmental and biomedical hazards, their physiology and emergent behaviors could be leveraged for synthetic biology to engineer more capable and robust bacteria. Specifically, bacteria within biofilms participate in complex emergent behaviors such as collective organization, cell-to-cell signaling, and division of labor. Understanding and utilizing these properties can enable the effective deployment of engineered bacteria into natural target environments. Toward this goal, this review summarizes the current state of synthetic biology in biofilms by highlighting new molecular tools and remaining biological challenges. Looking to future opportunities, advancing synthetic biology in biofilms will enable the next generation of smart cell-based technologies for use in medicine, biomanufacturing, and environmental remediation.     

The winemaker's bug: From ancient wisdom to opening new vistas with frontier yeast science

The past three decades have seen a global wine glut. So far, well-intended but wasteful and expensive market-intervention has failed to drag the wine industry out of a chronic annual oversupply of roughly 15%. Can yeast research succeed where these approaches have failed by providing a means of improving wine quality, thereby making wine more appealing to consumers? To molecular biologists Saccharomyces cerevisiae is as intriguing as it is tractable. A simple unicellular eukaryote, it is an ideal model organism, enabling scientists to shed new light on some of the biggest scientific challenges such as the biology of cancer and aging. It is amenable to almost any modification that modern biology can throw at a cell, making it an ideal host for genetic manipulation, whether by the application of traditional or modern genetic techniques. To the winemaker, this yeast is integral to crafting wonderful, complex wines from simple, sugar-rich grape juice. Thus any improvements that we can make to wine, yeast fermentation performance or the sensory properties it imparts to wine will benefit winemakers and consumers. With this in mind, the application of frontier technologies, particularly the burgeoning fields of systems and synthetic biology, have much to offer in their pursuit of "novel" yeast strains to produce high quality wine. This paper discusses the nexus between yeast research and winemaking. It also addresses how winemakers and scientists face up to the challenges of consumer perceptions and opinions regarding the intervention of science and technology; the greater this intervention, the stronger the criticism that wine is no longer "natural." How can wine researchers respond to the growing number of wine commentators and consumers who feel that scientific endeavors favor wine quantity over quality and "technical sophistication, fermentation reliability and product consistency" over "artisanal variation"? This paper seeks to present yeast research in a new light and a new context, and it raises important questions about the direction of yeast research, its contribution to science and the future of winemaking.     

The synthetic biology puzzle: a qualitative study on public reflections towards a governance framework

Synthetic biology is currently one of the most debated emerging biotechnologies. The societal assessment of this technology is primarily based on contributions by scientists and policy makers, who focus mainly on technical challenges and possible risks. While public dialogue is given, it is yet rather limited. This study explores public debates concerning synthetic biology based on a focus group study with citizens from Austria and Germany and contextualises the analysed public views with content from policy reports and previous empirical studies on public engagement. The findings suggest that discussants favoured a gradual implementation process of synthetic biology, which is receptive to questions about the distribution of possible benefits. The discussed topics correspond in many ways with content from policy reports and former investigations, yet the emphasis of the discussions was different for many aspects.     

Carbon-negative synthetic biology: challenges and emerging trends of cyanobacterial technology

Global warming and climate instability have spurred interest in using renewable carbon resources for the sustainable production of chemicals. Cyanobacteria are ideal cellular factories for carbon-negative production of chemicals owing to their great potentials for directly utilizing light and CO₂ as sole energy and carbon sources, respectively. However, several challenges in adapting cyanobacterial technology to industry, such as low productivity, poor tolerance, and product harvesting difficulty, remain. Synthetic biology may finally address these challenges. Here, we summarize recent advances in the production of value-added chemicals using cyanobacterial cell factories, particularly in carbon-negative synthetic biology and emerging trends in cyanobacterial applications. We also propose several perspectives on the future development of cyanobacterial technology for commercialization.     

Drug discovery and development for neglected parasitic diseases

Diseases caused by tropical parasites affect hundreds of millions of people worldwide but have been largely neglected for drug development because they affect poor people in poor regions of the world. Most of the current drugs used to treat these diseases are decades old and have many limitations, including the emergence of drug resistance. This review will summarize efforts to reinvigorate the drug development pipeline for these diseases, which is driven in large part by support from major philanthropies. The organisms responsible for these diseases have a fascinating biology, and many potential biochemical targets are now apparent. These neglected diseases present unique challenges to drug development that are being addressed by new consortia of scientists from academia and industry.     

Synthetic biology: ethical ramifications 2009

During 2007 and 2008 synthetic biology moved from the manifesto stage to research programs. As of 2009, synthetic biology is ramifying; to ramify means to produce differentiated trajectories from previous determinations. From its inception, most of the players in synthetic biology agreed on the need for (a) rationalized design and construction of new biological parts, devices, and systems as well as (b) the re-design of natural biological systems for specified purposes, and that (c) the versatility of designed biological systems makes them suitable to address such challenges as renewable energy, the production of inexpensive drugs, and environmental remediation, as well as providing a catalyst for further growth of biotechnology. What is understood by these goals, however, is diverse. Those assorted understandings are currently contributing to different ramifications of synthetic biology. The Berkeley Human Practices Lab, led by Paul Rabinow, is currently devoting its efforts to documenting and analyzing these ramifications as they emerge.     

Education and training for radiation scientists: radiation research program and American Society of Therapeutic Radiology and Oncology Workshop, Bethesda, Maryland, May 12-14, 2003

Current and potential shortfalls in the number of radiation scientists stand in sharp contrast to the emerging scientific opportunities and the need for new knowledge to address issues of cancer survivorship and radiological and nuclear terrorism. In response to these challenges, workshops organized by the Radiation Research Program (RRP), National Cancer Institute (NCI) (Radiat. Res. 157, 204-223, 2002; Radiat. Res. 159, 812-834, 2003), and National Institute of Allergy and Infectious Diseases (NIAID) (Nature, 421, 787, 2003) have engaged experts from a range of federal agencies, academia and industry. This workshop, Education and Training for Radiation Scientists, addressed the need to establish a sustainable pool of expertise and talent for a wide range of activities and careers related to radiation biology, oncology and epidemiology. Although fundamental radiation chemistry and physics are also critical to radiation sciences, this workshop did not address workforce needs in these areas. The recommendations include: (1) Establish a National Council of Radiation Sciences to develop a strategy for increasing the number of radiation scientists. The strategy includes NIH training grants, interagency cooperation, interinstitutional collaboration among universities, and active involvement of all stakeholders. (2) Create new and expanded training programs with sustained funding. These may take the form of regional Centers of Excellence for Radiation Sciences. (3) Continue and broaden educational efforts of the American Society for Therapeutic Radiology and Oncology (ASTRO), the American Association for Cancer Research (AACR), the Radiological Society of North America (RSNA), and the Radiation Research Society (RRS). (4) Foster education and training in the radiation sciences for the range of career opportunities including radiation oncology, radiation biology, radiation epidemiology, radiation safety, health/government policy, and industrial research. (5) Educate other scientists and the general public on the quantitative, basic, molecular, translational and applied aspects of radiation sciences.     

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.     

Designer metalloenzymes for synthetic biology: Enzyme hybrids for catalysis

Combining organometallics and biology has generated broad interest from scientists working on applications from in situ drug release to biocatalysis. Engineered enzymes and biohybrid catalysts (also referred to as artificial enzymes) have introduced a wide range of abiotic chemistry into biocatalysis. Predominantly, this work has concentrated on using these catalysts for single step in vitro reactions. However, the promise of using these hybrid catalysts in vivo and combining them with synthetic biology and metabolic engineering is vast. This report will briefly review recent advances in artificial metalloenzyme design, followed by summarising recent studies that have looked at the use of these hybrid catalysts in vivo and in enzymatic cascades, therefore exploring their potential for synthetic biology.     

Synthetic biology confronts publics and policy makers: challenges for communication, regulation and commercialization

The novelty of synthetic biology lies in the use of synthesized parts that can be arranged to make useful products. Such advanced, high-throughput genetic engineering projects redesign and fabricate existing biological systems as well as new biological parts, devices and systems that do not occur in nature. This Opinion discusses challenges raised by synthetic biology for public acceptance, regulation, commercialization and the emerging global issue of access to genetic resources and information. As with all new fields of research, maintaining the trust of the public and policy regulators is paramount. Hype and exaggerated claims are counterproductive to developing adaptive and ethically sound regulatory models responsive to stakeholder concerns.     

The development, regulation and use of biopesticides for integrated pest management

Over the past 50 years, crop protection has relied heavily on synthetic chemical pesticides, but their availability is now declining as a result of new legislation and the evolution of resistance in pest populations. Therefore, alternative pest management tactics are needed. Biopesticides are pest management agents based on living micro-organisms or natural products. They have proven potential for pest management and they are being used across the world. However, they are regulated by systems designed originally for chemical pesticides that have created market entry barriers by imposing burdensome costs on the biopesticide industry. There are also significant technical barriers to making biopesticides more effective. In the European Union, a greater emphasis on Integrated Pest Management (IPM) as part of agricultural policy may lead to innovations in the way that biopesticides are regulated. There are also new opportunities for developing biopesticides in IPM by combining ecological science with post-genomics technologies. The new biopesticide products that will result from this research will bring with them new regulatory and economic challenges that must be addressed through joint working between social and natural scientists, policy makers and industry.     

从人类基因组到人造生命:克雷格·文特尔领路生命科学

2010年5月20日,美国Science杂志报道J.Craig Venter的研究小组制造了第一个能够自我复制的人工合成生命,并立即引发了人们对这一研究潜在威胁的担忧和有关生物安全和生物伦理的讨论。但同时,这一成果也是人类在合成生物学领域的一次突破。我们相信在后基因组时代,合成生物学的发展必将广泛地应用于能源、环境、材料、医药等诸多领域,从而影响和改变人类未来的生活。     

Shaping the science–industry–policy interface in synthetic biology

Current advances in the emerging field of synthetic biology and the improvements in key technologies promise great impacts, not only on future scientific development, but also on the economy. In this paper we will adopt the triple helix concept for analyzing the early stages of a new field of science and innovation, namely synthetic biology. Synthetic biology is based on the creation and assembly of parts in order to create new and more complex structures and functions. These features of synthetic biology raise questions related to standardization and intellectual property, but also to security and public perception issues that go beyond the classical biotechnology discussions. These issues concern all involved actors in the synthetic biology field and affect the interrelationship between science, industry and policy. Based on the results of the recently finished EU FP-6 funded project TESSY (http://www.tessy-europe.de), the article analyzes these issues. Additionally, it illustrates the setting of clear framework conditions for synthetic biology research and development and the identification and definition of common goals for the future development of the field which will be needed for efficient science–industry–policy interaction. It was shown that it will be crucial to develop approaches that consider the needs of science and industry, on the one hand, and comply with the expectations of society, on the other hand. As synthetic biology is a global activity, the involvement of national decision-makers in international initiatives will further stimulate the development of the field.     

Citizen science and wildlife biology: Synergies and challenges

Citizen science (CS) has evolved over the past decades as a working method involving interested citizens in scientific research, for example by reporting observations, taking measurements or analysing data. In the past, research on animal behaviour has been benefitting from contributions of citizen scientists mainly in the field of ornithology but the full potential of CS in ecological and behavioural sciences is surely still untapped. Here, we present case studies that successfully applied CS to research projects in wildlife biology and discuss potentials and challenges experienced. Our case studies cover a broad range of opportunities: large‐scale CS projects with interactive online tools on bird song dialects, engagement of stakeholders as citizen scientists to reduce human–wildlife conflicts, involvement of students of primary and secondary schools in CS projects as well as collaboration with the media leading to successful recruitment of citizen scientists. Each case study provides a short overview of the scientific questions and how they were approached to showcase the potentials and challenges of CS in wildlife biology. Based on the experience of the case studies, we highlight how CS may support research in wildlife biology and emphasise the value of fostering communication in CS to improve recruitment of participants and to facilitate learning and mutual trust among different groups of interest (e.g., researchers, stakeholders, students). We further show how specific training for the participants may be needed to obtain reliable data. We consider CS as a suitable tool to enhance research in wildlife biology through the application of open science procedures (i.e., open access to articles and the data on publicly available repositories) to support transparency and sharing experiences.     

国际基因工程机器大赛在中国

合成生物学是一门新兴的交叉学科,为培养合成生物学后备人才,国际基因工程机器(iGEM)大赛应运而生。2007年中国首次有5支队伍参加iGEM大赛,至今已经有11年的历史。然而,目前尚无全面总结中国iGEM队伍的相关文献。文中全面梳理和总结了iGEM大赛在中国的发展历程,包括参赛队伍的数量、地理分布、竞赛成绩、中国iGEM社群CCiC的发展情况,以及iGEM大赛对中国高等教育的促进和借鉴作用,并深度思考了iGEM大赛在中国的发展前景,提出了发展建议。随着我国高等教育"双一流"战略的实施,iGEM大赛在我国的发展具有光明的前景,可为培养新一代科学家作出更大的贡献。     

Meeting report: Synthetic DNA - Writing with the Letters of Life: January 24, 2012, Frankfurt, Germany

The one-day meeting on Synthetic DNA (January 24, 2012) organized by and held at the DECHEMA in Frankfurt attracted about 100 participants from academia and industry interested in synthesizing DNA and its applications in synthetic biology. In recent years the cost for synthetic DNA reduced from 7€/bp to 0.35€/bp which has opened up many new possibilities for molecular biology. You can purchase the gene, cDNA, oligo library or full vector specifically for a particular expression host and apply synthetic biology principles to produce or create new drugs, vaccines or any other biotechnological products. There are, however, great concerns within society to produce organisms that do not exist in nature, and the potential misuse of them. Adressing these concerns and to use a clear terminology that do not cause misunderstandings are important issues within the field, which were also discussed at this meeting.