Synthetic biology: building the language for a new science brick by metaphorical brick

Changes in the biosciences and their relations to society over the last decades provide a unique opportunity to examine whether or not such changes leave traces in the language we use to talk about them. In this article we examine metaphors used in English-speaking press coverage to conceptualize a new type of (interdisciplinary) bioscience: synthetic biology. Findings show that three central metaphors were used between 2008 and May 2010. They exploit social and cultural knowledge about books, computers and engines and are linked to knowledge of three revolutions in science and society (the printing, information and industrial revolutions). These three central metaphors are connected to each other through the concepts of reading/writing, designing and mass production and they focus on science as a revolutionary process rather than on the end results or products of science. Overall, we observed the use of a complex bricolage of mixed metaphors and chains of metaphors that root synthetic biology in historical events and achievements, while at the same time extolling its promises for the future.     

Metaphors in search of a target: the curious case of epigenetics

Carrying out research in genetics and genomics and communicating about them would not be possible without metaphors such as “information,” “code,” “letter” or “book.” Genetic and genomic metaphors have remained relatively stable for a long time but are now beginning to shift in the context of synthetic biology and epigenetics. This article charts the emergence of metaphors in the context of epigenetics, first through collecting some examples of metaphors in scientific and popular writing and second through a systematic analysis of metaphors used in two UK broadsheets. Findings show that while source domains for metaphors can be identified, such as our knowledge of electrical switches or of bookmarks, it is difficult to pinpoint target domains for such metaphors. This may be indicative both of struggles over what epigenetics means for scientists (natural and social) and of difficulties associated with talking about this, as yet, young field in the popular press.     

Snail shell coiling (re-)evolution and the evo-devo revolution

During the last two decades evolutionary developmental biology has become a major research programme whose findings put into question some concepts lying at the core of the 'Synthetic Theory'. However, some authors are waiting for a 'revolution' in biology, one in which the existing genetic determinism will give way to a new conceptual understanding of the complexity of living organisms. This 'revolution' should necessarily pass through the elaboration of an appropriate theoretical framework integrating the non-linear dynamics of development as its fundamental basis. This objective implies a drastic shift in the way causality is generally understood as well as a purge of numerous convenient but misleading metaphors such as genetic or developmental programmes. Although most authors do not take these metaphors too literally, some persist in employing such 'instructionist' notions in a more literal perspective, and, in doing so, deny some concepts at the core of evolutionary developmental biology. We critically review two recent studies suggesting that shell coiling has re-evolved in a family of limpets (Calyptraeidae, Gastropoda). We stress that this putative re-evolution of snail shell coiling results only from an arbitrary scoring procedure leading us to consider shell coiling as a binary discrete character. We show that the way in which these authors connect this case study to evolutionary theories stems from the unwarranted premise of a linear mapping of genes onto phenotypes where particulate inheritance of morphological characters seems implicitly assumed. We illustrate how the persisting unclear role of genes in morphogenesis allows the maintenance of the adaptationist programme.     

Mobilizing metaphors: the popular use of keystone,flagship and umbrella species concepts

Misrepresentation of terminology is a major impediment for attempts at enhancing public conservation literacy. Despite being critically important for improving conservation practice, there have been few systematic analyses of the popular use of conservation terminology. This paper draws from science communication studies and metaphor analysis, to examine how keystone, flagship and umbrella species concepts are used and represented in non-academic contexts. 557 news articles containing these terms were systematically analyzed. Mammals featured in 60% of articles on keystones, 55% on flagships and 63% on umbrella species. Number of articles explaining the terms keystone (35%) and flagship (31%) was low, and keystones were the most misrepresented term. Keystones were metaphorically linked with balance, flagships with representation and umbrella species with protection. These metaphors influenced public interpretation of scientific terminology, oriented actions towards select species, and led to a valuation of such actions. Together, the findings highlight three important aspects of popular use of conservation terminology: (1) communication is largely biased towards mammals, (2) everyday language plays a vital role in the interpretation of concepts, and (3) metaphors influence peoples’ actions and understanding. Conservation biologists need to engage with issues of language if public conservation literacy is to be improved. Further evaluations of concepts with high public and policy relevance, systematic identification of communication shortfalls, and linguistic assessments prior to promoting new terms are potential ways of achieving this.     

The Mathematical Basis of Mendelian Genetics

In a climate where increasing numbers of students are encouraged to pursue post-secondary education, the level of preparedness students have for college-level coursework is not far from the minds of all educators, especially high school teachers. Specifically within the biological sciences, introductory biology classes often serve as the gatekeeper or a pre-requisite for subsequent coursework in those fields and pre-professional programmes (eg pre-medicine or pre-veterinarian). Thus, how helpful high school science and mathematics experiences are in preparing students for their introductory biology classes is important and relevant for teachers, science educators and policy makers alike. This quantitative study looked at the association between students' high school science and mathematics experiences with introductory college biology performance. Using a nationally representative sample of US students (n?=?2667) enrolled in 33 introductory college biology courses, a multi-level statistical model was developed to analyse the association between high school educational experiences and the final course grade in introductory biology courses. Advanced high school science and mathematics coursework, an emphasis on a deep conceptual understanding of biology concepts and a prior knowledge of concepts addressed in well-structured laboratory investigations are all positively associated with students' achievement in introductory college biology.     

Reverse engineering the embryo: a graduate course in developmental biology for engineering students at the University of Manitoba,Canada

Our desire to educate engineers to be able to understand the component processes of embryogenesis, is driven by the notion that only when principles borrowed from mathematics, fluid mechanics, materials science, etc. are applied to classical problems in developmental biology, will sufficient comprehension be achieved to permit successful understanding and therapeutic manipulation of embryos. As it now stands, biologists seldom possess either skills or interest in those areas of endeavor. Thus, we have determined that it is easier to educate engineers in the principles of developmental biology than to help biologists deal with the complexities of engineering. We describe a graduate course that has been taken, between 1999 and 2002, by 17 engineering students. Our goal is to prepare them to reverse engineer the embryo, i.e., to look at it as an object or process whose construction, albeit self-construction, might be explicable in terms of engineering principles applied at molecular, cellular and whole embryo levels.     

A journey from reductionist to systemic cell biology aboard the schooner Tara

In this essay I describe my personal journey from reductionist to systems cell biology and describe how this in turn led to a 3-year sea voyage to explore complex ocean communities. In describing this journey, I hope to convey some important principles that I gleaned along the way. I realized that cellular functions emerge from multiple molecular interactions and that new approaches borrowed from statistical physics are required to understand the emergence of such complex systems. Then I wondered how such interaction networks developed during evolution. Because life first evolved in the oceans, it became a natural thing to start looking at the small organisms that compose the plankton in the world's oceans, of which 98% are … individual cells-hence the Tara Oceans voyage, which finished on 31 March 2012 in Lorient, France, after a 60,000-mile around-the-world journey that collected more than 30,000 samples from 153 sampling stations.     

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 relativity of Darwinian populations and the ecology of endosymbiosis

If there is a single discipline of science calling the basic concepts of biology into question, it is without doubt microbiology. Indeed, developments in microbiology have recently forced us to rethink such fundamental concepts as the organism, individual, and genome. In this paper I show how microorganisms are changing our understanding of natural aggregations and develop the concept of a Darwinian population to embrace these discoveries. I start by showing that it is hard to set the boundaries of a Darwinian population, and I suggest thinking of a Darwinian population as a relative property of a Darwinian individual. Then I argue, in contrast to the commonly held view, that Darwinian populations are multispecies units, and that in order to accept the multispecies account of Darwinian populations we have to separate fitness from natural selection. Finally, I show how all these ideas provide a theoretical framework leading to a more precise understanding of the ecology of endosymbiosis than is afforded by poetic metaphors such as ‘slavery’.     

Systems biology as a foundation for genome-scale synthetic biology

As the ambitions of synthetic biology approach genome-scale engineering, comprehensive characterization of cellular systems is required, as well as a means to accurately model cell-scale molecular interactions. These requirements are coincident with the goals of systems biology and, thus, systems biology will become the foundation for genome-scale synthetic biology. Systems biology will form this foundation through its efforts to reconstruct and integrate cellular systems, develop the mathematics, theory and software tools for the accurate modeling of these integrated systems, and through evolutionary mechanisms. As genome-scale synthetic biology is so enabled, it will prove to be a positive feedback driver of systems biology by exposing and forcing researchers to confront those aspects of systems biology which are inadequately understood.     

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.     

Synthetic biology and genetic causation

Synthetic biology research is often described in terms of programming cells through the introduction of synthetic genes. Genetic material is seemingly attributed with a high level of causal responsibility. We discuss genetic causation in synthetic biology and distinguish three gene concepts differing in their assumptions of genetic control. We argue that synthetic biology generally employs a difference-making approach to establishing genetic causes, and that this approach does not commit to a specific notion of genetic program or genetic control. Still, we suggest that a strong program concept of genetic material can be used as a successful heuristic in certain areas of synthetic biology. Its application requires control of causal context, and may stand in need of a modular decomposition of the target system. We relate different modularity concepts to the discussion of genetic causation and point to possible advantages of and important limitations to seeking modularity in synthetic biology systems.     

Again on language of biology]

Some time ago I proposed in an Editorial in this journal some considerations on the language of biology. I concluded that, to realize an autonomy of such a language (and therefore of biology), we have to develop a valid language for biology. In such a context, it seemed to me that the term "metaphors" referred to the concepts concerning the information carried by genetic code, was a reasonable one. However, Barbieri's article in this issue of Rivista di Biologia / Biology Forum calls for a reply. Of course, we do not know very much in this field, even if we have some evidence that a sequence of bases on a DNA is not determined only by chance. In any case we can exclude that nature in this occasion has "invented" a code. Nature doesn't "invent" anything: it only follows its rules, that we name "laws of nature". Barbieri quotes the Morse code, but forgets to say that such a code is "conventional" in the sense that it is valid only because it is the result of an "agreement" between Morse and the users of that code. There is nothing more unnatural than a "code": with whom nature should actually have to "reach an agreement"? As a matter of fact, we interpret as "information" what happens by law of nature. Also Barbieri's thesis that genes and proteins are molecular artifacts, assembled by external agents, whereas generally molecules are determined by their bonds, i.e. by internal factors, is a disputable one. It is examined how much an external structure plays a role in ordinary chemical reactions. The "information" of physics is not a semantic information. For such information we can refer to history of literature, telegraphic offices, genetics or biochemistry.     

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.     

Synthetic biology of minimal systems

“Synthetic biology” is a concept that has developed together with, or slightly after, “systems biology”. But while systems biology aims at the full understanding of large systems by integrating more and more details into their models, synthetic biology phrases different questions, namely: what particular biological function could be obtained with a certain known subsystem of reduced complexity; can this function be manipulated or engineered in artificial environments or genetically modified organisms; and if so, how? The most prominent representation of synthetic biology has so far been microbial engineering by recombinant DNA technology, employing modular concepts known from information technology. However, there are an increasing number of biophysical groups who follow similar strategies of dissecting cellular processes and networks, trying to identify functional minimal modules that could then be combined in a bottom-up approach towards biology. These modules are so far not as particularly defined by their impact on DNA processing, but rather influenced by core fields of biophysics, such as cell mechanics and membrane dynamics. This review will give an overview of some classical and some quite new biophysical strategies for constructing minimal systems of certain cellular modules. We will show that with recent advances in understanding of cytoskeletal and membrane elements, the time might have come to experimentally challenge the concept of a minimal cell.     

TinkerCell: modular CAD tool for synthetic biology

Background

Synthetic biology brings together concepts and techniques from engineering and biology. In this field, computer-aided design (CAD) is necessary in order to bridge the gap between computational modeling and biological data. Using a CAD application, it would be possible to construct models using available biological "parts" and directly generate the DNA sequence that represents the model, thus increasing the efficiency of design and construction of synthetic networks.

Results

An application named TinkerCell has been developed in order to serve as a CAD tool for synthetic biology. TinkerCell is a visual modeling tool that supports a hierarchy of biological parts. Each part in this hierarchy consists of a set of attributes that define the part, such as sequence or rate constants. Models that are constructed using these parts can be analyzed using various third-party C and Python programs that are hosted by TinkerCell via an extensive C and Python application programming interface (API). TinkerCell supports the notion of a module, which are networks with interfaces. Such modules can be connected to each other, forming larger modular networks. TinkerCell is a free and open-source project under the Berkeley Software Distribution license. Downloads, documentation, and tutorials are available at http://www.tinkercell.com.

Conclusion

An ideal CAD application for engineering biological systems would provide features such as: building and simulating networks, analyzing robustness of networks, and searching databases for components that meet the design criteria. At the current state of synthetic biology, there are no established methods for measuring robustness or identifying components that fit a design. The same is true for databases of biological parts. TinkerCell's flexible modeling framework allows it to cope with changes in the field. Such changes may involve the way parts are characterized or the way synthetic networks are modeled and analyzed computationally. TinkerCell can readily accept third-party algorithms, allowing it to serve as a platform for testing different methods relevant to synthetic biology.     

Synthetic biology between technoscience and thing knowledge

Synthetic biology presents a challenge to traditional accounts of biology: Whereas traditional biology emphasizes the evolvability, variability, and heterogeneity of living organisms, synthetic biology envisions a future of homogeneous, humanly engineered biological systems that may be combined in modular fashion. The present paper approaches this challenge from the perspective of the epistemology of technoscience. In particular, it is argued that synthetic-biological artifacts lend themselves to an analysis in terms of what has been called ‘thing knowledge’. As such, they should neither be regarded as the simple outcome of applying theoretical knowledge and engineering principles to specific technological problems, nor should they be treated as mere sources of new evidence in the general pursuit of scientific understanding. Instead, synthetic-biological artifacts should be viewed as partly autonomous research objects which, qua their material-biological constitution, embody knowledge about the natural world—knowledge that, in turn, can be accessed via continuous experimental interrogation.     

Concepts and schemes for the re-engineering of physical protein modules: generating nanodevices via targeted replacements with constrained amino acids

Physically building complex multi-molecular structures from naturally occurring biological macromolecules has aroused a great deal of interest. Here we focus on nanostructures composed of re-engineered, natural 'foldamer' building blocks. Our aim is to provide some of the underlying concepts and schemes for crafting structures utilizing such conformationally relatively stable molecular components. We describe how, via chemical biology strategies, it is further possible to chemically manipulate the foldamer building blocks toward specific shape-driven structures, which in turn could be used toward potential-designed functions. We outline the criteria in choosing candidate foldamers from the vast biological repertoire, and how to enhance their stability through selected targeted replacements by non-proteinogenic conformationally constrained amino acids. These approaches combine bioinformatics, high performance computations and mathematics with synthetic organic chemistry. The resulting artificially engineered self-organizing molecular scale structures take advantage of nature's nanobiology toolkit and at the same time improve on it, since their new targeted function differs from that optimized by evolution. The major challenge facing nanobiology is to be able to exercise fine control over the performance of these target-specific molecular machines.     

A consistent terminology for quantifying species diversity? Yes, it does exist

The prevailing terminological confusion around the concept ‘diversity’ has hampered accurate communication and caused diversity issues to appear unnecessarily complicated. In fact, a consistent terminology for phenomena related to (species) diversity is already available. When this terminology is adhered to, diversity emerges as an easily understood concept. It is important to differentiate between diversity itself and a diversity index: an index of something is just a surrogate for the thing itself. The conceptual problem of defining diversity also has to be separated from the practical problem of deciding how to adequately quantify diversity for a community of interest. In practice, diversity can be quantified for any dataset where units of observation (such as individuals) have been classified into types (such as species). All that needs to be known is what proportion of the observed units belong to a type of mean abundance. Diversity equals the inverse of this mean, and it quantifies the effective number of the types of interest. In ecology, interest often (but not always) focuses on species diversity. If the dataset consists of (or gets divided into) subunits, then the total effective number of species (gamma diversity) can be partitioned into the effective number of compositionally distinct subunits (beta diversity) and the mean effective number of species per such subunit (alpha diversity). Species richness is related to species diversity, but they are not the same thing; richness does not take the proportional abundances into account and is therefore the actual—rather than the effective—number of types. Most of the phenomena that have been called ‘beta diversity’ in the past do not quantify an effective number of types, so they should be referred to by names other than ‘diversity’ (for example, species turnover or differentiation).