Biologists are nearing the creation of the first fully synthetic eukaryotic genome. Does this mean that we still soon be able to create genomes that are parts of an existing genetic lineage? If so, it might be possible to bring back extinct species. But do genomes that are synthetically assembled, no matter how similar they are to native genomes, really belong to the genetic lineage on which they were modelled? This article will argue that they are situated within the (...) same genetic lineage. To see why requires closely examining whether material overlap between parents and offspring is a necessary feature of biological reproduction. The processes used to create synthetic genomes shows that these processes are a form of scaffolded reproduction because they use external machinery and take ownership of the material parts used to create synthetic genomes. Closely examining these processes also reveals, surprisingly, that ‘synthetic reproduction’ can take place between entities that don’t participate in the same biological lineages. 1Introduction2The Argument for Lineage-less Genomes3Synthetic Eukaryotic Chromosomes and Material Overlap4Biological Reproduction, Material, and Information5Synthetic Reproductive Processes and Their Implications. (shrink)

The topic of synthetic life has long been a subject for science fiction writers, philosophers, and even scientists. With the announcement in 2010 by renowned biologist J. Craig Venter that he and a team of scientists from the J. Craig Venter Institute (JCVI) had created a bacterial cell with chemically synthesized genome, discussions of synthetic life were no longer just conjecture.Humans had assembled nonliving components to make a living cell (Gibson et al. 2010). I was one of the (...) leaders of that endeavor, and this article will be a first-person account of how we made our cell, along with my conjectures about what will come next in the new fields of synthetic biology and synthetic genomics.Scanning electron .. (shrink)

This article examines how minimal genome research mobilizes philosophical concepts such as minimality and essentiality. Following a historical approach the article aims to uncover what function this terminology plays and which problems are raised by them. Specifically, four historical moments are examined, linked to the work of Harold J. Morowitz, Mitsuhiro Itaya, Eugene Koonin and Arcady Mushegian, and J. Craig Venter. What this survey shows is a historical shift away from historical questions about life or descriptive questions about specific organisms (...) towards questions that explore biological possibilities: what are possible forms of minimal genomes, regardless of whether they exist in nature? Moreover, it highlights a fundamental ambiguity at work in minimal genome research between a universality claim and a standardization claim: does a minimal genome refer to the minimal gene set for any organism whatsoever? Or does it refer rather to a gene set that will provide stable, robust and predictable behaviour, suited for biotechnological applications? Two diagnoses are proposed for this ambiguity: a philosophical diagnosis of how minimal genome research either misunderstands the ontology of biological entities or philosophically misarticulates scientific practice. Secondly, a historical diagnosis that suggests that this ambiguity is part of a broader shift towards technoscience. (shrink)

The SynBioSecurity argument says that synthetic biology introduces new risks of intentional misuse of synthetic pathogens and that, therefore, there is a need for extra regulations and oversight. This paper provides an analysis of the argument, sets forth a new version of it, and identifies three developments that raise biosecurity risks compared to the situation earlier. The developments include a spread of the required know-how, improved availability of the techniques, instruments and biological parts, and new technical possibilities such (...) as “resurrecting” disappeared pathogens. It is first shown that the general argument from SynBioSecurity needs to be qualified and that many improvements to biosecurity have already been implemented, most notably in the United States. Second, I suggest a new strain of the argument: the situation that most branches of synthetic biology fall under the gene technology regulation in the European Union and that this regulation in its current form does not adequately address SynBioSecurity risks together provide a weighty reason to review and possibly refine the legislation as well as the supervisory practices. Ethically speaking, the rise in the relative risk of bioterrorism brings to the fore new extrinsic issues. (shrink)

Synthetic genomics is a new field of research in which small DNA pieces are assembled in a series of steps into whole genomes. The highly reduced genomes of host‐associated bacteria are now being used as models for de novo synthesis of small genomes in the laboratory. Bacteria with the smallest genomes identified in nature provide nutrients to their hosts, such as amino acids, co‐factors and vitamins. Comparative genomics of these bacteria enables predictions to be made about the (...) gene sets required for core cellular functions and the associated metabolic network for the biosynthesis of host‐selected compounds. Synthetic biology may ultimately enable researchers to make customized cell‐specific organelles for the production and delivery of drugs to humans and domestic animals. Synthetic genomics may also become the method of choice for functional analyses of genes and genomes from bacteria that cannot be cultivated in the laboratory. (shrink)

This text answers the question, posed by the editor, on the philosophical and social issues resulting from the synthetic assembly of a modified bacterial genome that was introduced in an existing bacterial species (M.mycoides)and so it was claimed to represent the first ever kind of synthetic life produced by human manipulation.

In various documents the view emerges that contemporary biotechnosciences are currently experiencing a scientific revolution: a massive increase of pace, scale and scope. A significant part of the research endeavours involved in this scientific upheaval is devoted to understanding and, if possible, ameliorating humankind: from our genomes up to our bodies and brains. New developments in contemporary technosciences, such as synthetic biology and other genomics and “post-genomics” fields, tend to blur the distinctions between prevention, therapy and enhancement. (...) An important dimension of this development is “biomimesis”: i.e. the tendency of novel technologies and materials to mimic or plagiarize nature on a molecular and microscopic level in order to optimise prospects for the embedding of technological artefacts in natural systems such as human bodies and brains. In this paper, these developments are read and assessed from a psychoanalytical perspective. Three key concepts from psychoanalysis are used to come to terms with what is happening in research laboratories today. After assessing the general profile of the current revolution in this manner, I will focus on a particular case study, a line of research that may serve as exemplification of the vicissitudes of contemporary technosciences, namely viral biomaterials. Viral life forms can be genetically modified (their genomes can be rewritten) in such a manner that they may be inserted in human bodies in order to produce substances at specific sites such as hormones (testosterone), neurotransmitters (dopamine), enzymes (insulin) or bone and muscle tissue. Notably, certain target groups such as top athletes, soldiers or patients suffering from degenerative diseases may become the pioneers serving as research subjects for novel applications. The same technologies can be used for various purposes ranging from therapy up to prevention and enhancement. (shrink)

Synthetic biology is an emerging engineering discipline that attempts to design and rewire biological components, so as to achieve new functions in a robust and predictable manner. The new tools and strategies provided by synthetic biology have the potential to improve therapeutics for neurodegenerative diseases. In particular, synthetic biology will help design small molecules, proteins, gene networks, and vectors to target disease‐related genes. Ultimately, new intelligent delivery systems will provide targeted and sustained therapeutic benefits. New treatments will (...) arise from combining ‘protect and repair’ strategies: the use of drug treatments, the promotion of neurotrophic factor synthesis, and gene targeting. Going beyond RNAi and artificial transcription factors, site‐specific genome modification is likely to play an increasing role, especially with newly available gene editing tools such as CRISPR/Cas9 systems. Taken together, these advances will help develop safe and long‐term therapies for many brain diseases in human patients. (shrink)

Paul Thompson argues that current synthetic biology amounts to synthetic genomics, comprising a ‘platform’ technology, and that Christopher Preston's deontological objections based on its supposed rejection of the historical process of evolution miscarry. This makes it surprising that Thompson's normative ethic consists in a deontological appeal to Kantian duties of imperfect obligation. Construed as obligations subject to choice, such constraints risk being excessively malleable where the ethical objections to deployment of this technology concern land rights and/or exploitation. (...) Thompson's advocacy of processes ‘more beneficial’ well illustrates another vulnerability; processes more beneficial than ones that undermine livelihoods could be best avoided themselves, although ones more beneficial than the status quo may not. He well argues that non-deontological arguments should not be confined to human survival, but neglects stances that are either biocentric, consequentialist, or both. Yet a truly synthetic bioethics would be likely to embody these characteristics. (shrink)

Top-down synthetic biology makes partly synthetic cells by redesigning simple natural forms of life, and bottom-up synthetic biology aims to make fully synthetic cells using only entirely nonliving components. Within synthetic biology the notions of complexity and emergence are quite controversial, but the imprecision of key notions makes the discussion inconclusive. I employ a precise notion of weak emergent property, which is a robust characteristic of the behavior of complex bottom-up causal webs, where a complex (...) causal web is one that is incompressible and its behavior cannot be derived except by crawling through all of the gory details of the interactions in the web. The central thesis of this article is that synthetic biology centrally is the activity of engineering the desired weak emergent properties of synthetic cells. Synthetic biology has many different ways to engineer desired weak emergent properties of synthetic cells, including Edisonian trial and error, standardized parts, refactoring, and reprogramming synthetic genomes. The article ends by noting two philosophical consequences of engineering weak emergence. One is epistemological: synthesis is crucial for discovering weak emergent properties. The other is metaphysical: simple life forms are nothing but complex chemical mechanisms. (shrink)

Synthetic biology is an increasingly high-profile area of research that can be understood as encompassing three broad approaches towards the synthesis of living systems: DNA-based device construction, genome-driven cell engineering and protocell creation. Each approach is characterized by different aims, methods and constructs, in addition to a range of positions on intellectual property and regulatory regimes. We identify subtle but important differences between the schools in relation to their treatments of genetic determinism, cellular context and complexity. These distinctions tie (...) into two broader issues that define synthetic biology: the relationships between biology and engineering, and between synthesis and analysis. These themes also illuminate synthetic biology's connections to genetic and other forms of biological engineering, as well as to systems biology. We suggest that all these knowledge-making distinctions in synthetic biology raise fundamental questions about the nature of biological investigation and its relationship to the construction of biological components and systems. (shrink)

Maintaining the coherence of the distinction between nature and artefact has long been central to environmental thinking. By building genomes from scratch out of 'bio-bricks', synthetic biology promises to create biotic artefacts markedly different from anything created thus far in biotechnology. These new biotic artefacts depart from a core principle of Darwinian natural selection – descent through modification – leaving them with no causal connection to historical evolutionary processes. This departure from the core principle of Darwinism presents a challenge (...) to the normative foundation of a number of leading positions in environmental ethics. As a result, environmental ethicists with a commitment to the normative significance of the historical evolutionary process may see synthetic biology as a moral 'line in the sand'. (shrink)

The scientific study of living organisms is permeated by machine and design metaphors. Genes are thought of as the ‘‘blueprint’’ of an organism, organisms are ‘‘reverse engineered’’ to discover their func- tionality, and living cells are compared to biochemical factories, complete with assembly lines, transport systems, messenger circuits, etc. Although the notion of design is indispensable to think about adapta- tions, and engineering analogies have considerable heuristic value (e.g., optimality assumptions), we argue they are limited in several important respects. In (...) particular, the analogy with human-made machines falters when we move down to the level of molecular biology and genetics. Living organisms are far more messy and less transparent than human-made machines. Notoriously, evolution is an oppor- tunistic tinkerer, blindly stumbling on ‘‘designs’’ that no sensible engineer would come up with. Despite impressive technological innovation, the prospect of artificially designing new life forms from scratch has proven more difficult than the superficial analogy with ‘‘programming’’ the right ‘‘software’’ would sug- gest. The idea of applying straightforward engineering approaches to living systems and their genomes— isolating functional components, designing new parts from scratch, recombining and assembling them into novel life forms—pushes the analogy with human artifacts beyond its limits. In the absence of a one-to-one correspondence between genotype and phenotype, there is no straightforward way to imple- ment novel biological functions and design new life forms. Both the developmental complexity of gene expression and the multifarious interactions of genes and environments are serious obstacles for ‘‘engi- neering’’ a particular phenotype. The problem of reverse-engineering a desired phenotype to its genetic ‘‘instructions’’ is probably intractable for any but the most simple phenotypes. Recent developments in the field of bio-engineering and synthetic biology reflect these limitations. Instead of genetically engi- neering a desired trait from scratch, as the machine/engineering metaphor promises, researchers are making greater strides by co-opting natural selection to ‘‘search’’ for a suitable genotype, or by borrowing and recombining genetic material from extant life forms. (shrink)

The scientific study of living organisms is permeated by machine and design metaphors. Genes are thought of as the ‘‘blueprint’’ of an organism, organisms are ‘‘reverse engineered’’ to discover their functionality, and living cells are compared to biochemical factories, complete with assembly lines, transport systems, messenger circuits, etc. Although the notion of design is indispensable to think about adaptations, and engineering analogies have considerable heuristic value (e.g., optimality assumptions), we argue they are limited in several important respects. In particular, the (...) analogy with human-made machines falters when we move down to the level of molecular biology and genetics. Living organisms are far more messy and less transparent than human-made machines. Notoriously, evolution is an opportunistic tinkerer, blindly stumbling on ‘‘designs’’ that no sensible engineer would come up with. Despite impressive technological innovation, the prospect of artificially designing new life forms from scratch has proven more difficult than the superficial analogy with ‘‘programming’’ the right ‘‘software’’ would suggest. The idea of applying straightforward engineering approaches to living systems and their genomes— isolating functional components, designing new parts from scratch, recombining and assembling them into novel life forms—pushes the analogy with human artifacts beyond its limits. In the absence of a one-to-one correspondence between genotype and phenotype, there is no straightforward way to implement novel biological functions and design new life forms. Both the developmental complexity of gene expression and the multifarious interactions of genes and environments are serious obstacles for ‘‘engineering’’ a particular phenotype. The problem of reverse-engineering a desired phenotype to its genetic ‘‘instructions’’ is probably intractable for any but the most simple phenotypes. Recent developments in the field of bio-engineering and synthetic biology reflect these limitations. Instead of genetically engineering a desired trait from scratch, as the machine/engineering metaphor promises, researchers are making greater strides by co-opting natural selection to ‘‘search’’ for a suitable genotype, or by borrowing and recombining genetic material from extant life forms. (shrink)

It is a most commonly accepted hypothesis that life originated from inanimate matter, somehow being a synthetic product of organic aggregates, and as such, a result of some sort of prebiotic synthetic biology. In the past decades, the newly formed scientific discipline of synthetic biology has set ambitious goals by pursuing the complete design and production of genetic circuits, entire genomes or even whole organisms. In this paper, I argue that synthetic biology might also shed some (...) novel and interesting perspectives on the question of the origin of life, and that, in addition, it might challenge our most commonly accepted definitions of life, thereby changing the ways we might think about life and its origin. (shrink)

Synthetic biology is an increasingly high‐profile area of research that can be understood as encompassing three broad approaches towards the synthesis of living systems: DNA‐based device construction, genome‐driven cell engineering and protocell creation. Each approach is characterized by different aims, methods and constructs, in addition to a range of positions on intellectual property and regulatory regimes. We identify subtle but important differences between the schools in relation to their treatments of genetic determinism, cellular context and complexity. These distinctions tie (...) into two broader issues that define synthetic biology: the relationships between biology and engineering, and between synthesis and analysis. These themes also illuminate synthetic biology's connections to genetic and other forms of biological engineering, as well as to systems biology. We suggest that all these knowledge‐making distinctions in synthetic biology raise fundamental questions about the nature of biological investigation and its relationship to the construction of biological components and systems. BioEssays 30:57–65, 2008. © 2007 Wiley Periodicals, Inc. (shrink)

The Presidential Commission for the Study of Bioethical Issues released its first report, New Directions: The Ethics of Synthetic Biology and Emerging Technologies, on December 16, 2010.1 President Barack Obama had requested this report following the announcement last year that the J. Craig Venter Institute had created the world’s first self-replicating bacterial cell with a completely synthetic genome. The Venter group’s announcement marked a significant scientific milestone in synthetic biology, an emerging field of research that aims to (...) combine the knowledge and methods of biology, engineering, and related disciplines in the design of chemically synthesized DNA to create organisms with novel or enhanced .. (shrink)

Synthetic biology emerged around 2000 as a new biological discipline. It shares with systems biology the same modular vision of organisms, but is more concerned with applications than with a better understanding of the functioning of organisms. A herald of this new discipline is Craig Venter who aims to create an artificial microorganism with the minimal genome compatible with life and to implement into it different 'functional modules' to generate new micro-organisms adapted to specific tasks. Synthetic biology is (...) based on the possibilities raised by genetic engineering, but it aims to engineer organisms, and not simply to modify them, mimicking the practice of computer engineers. Three points will be discussed: In what regard does synthetic biology represent a new epistemology of the life sciences? What are the relations between synthetic biology and evolutionary biology? What is the raison d'être of synthetic biology as a discipline independent of nanotechnologies? (shrink)

The aim of synthetic biology is to rationally design devices, systems, and organisms with desired innovative and useful functions (Slusarczyk, Lin, and Weiss 2012). To achieve this aim, synthetic biology uses a concept similar to engineering sciences: well-characterized and standardized modular biological building blocks are reassembled in a systematic and rational manner to generate complex devices and systems with a predicted function. In the past, molecular biological research in combination with intense work in new research areas like systems (...) biology and functional genomics revealed a large inventory of multifaceted modular biological parts that are now in the toolboxes of synthetic biologists. Due to .. (shrink)

We have synthesized a 582,970-base pair Mycoplasma genitalium genome. This synthetic genome, named M. genitalium JCVI-1.0, contains all the genes of wild-type M. genitalium G37 except MG408, which was disrupted by an antibiotic marker to block pathogenicity and to allow for selection. To identify the genome as synthetic, we inserted "watermarks" at intergenic sites known to tolerate transposon insertions. Overlapping "cassettes" of 5 to 7 kilobases (kb), assembled from chemically synthesized oligonucleotides, were joined by in vitro recombination to (...) produce intermediate assemblies of approximately 24 kb, 72 kb ("1/8 genome"), and 144 kb ("1/4 genome"), which were all cloned as bacterial artificial chromosomes in Escherichia coli. Most of these intermediate clones were sequenced, and clones of all four 1/4 genomes with the correct sequence were identified. The complete synthetic genome was assembled by transformation-associated recombination cloning in the yeast Saccharomyces cerevisiae, then isolated and sequenced. A clone with the correct sequence was identified. The methods described here will be generally useful for constructing large DNA molecules from chemically synthesized pieces and also from combinations of natural and synthetic DNA segments. 10.1126/science.1151721. (shrink)

Assembly of minimal genomes revealed many genes encoding unknown functions. Three overlooked functional categories account for some of them. Cells are prone to make errors and age. As a first key function, discrimination between proper and changed entities is indispensable. Discrimination requires management of information, an authentic, yet abstract, cur- rency of reality. For example proteins age, sometimes very fast. The cell must identify, then get rid of old proteins without destroying young ones. Implementing discrimination in cells leads to the (...) second set of functions, usually ignored. Being abstract, information must nevertheless be embodied into material entities, with unavoidable idiosyncratic properties. This brings about novel unmet needs. Hence, the buildup of cells elicits specific but awkward material implementations, ‘kludges’ that become essential under particular settings, while difficult to identify. Finally, a third functional category char- acterizes the need for growth, with metabolic implementations allowing the cell to put together the growth of its cytoplasm, membranes, and genome, spanning different spatial dimensions. Solving this metabolic quandary, critical for engineering novel synthetic biology chassis, uncovered an unexpected role for CTP synthetase as the coordinator of nonhomothetic growth. Because a significant number of SynBio constructs aim at creating cell factories we expect that they will be attacked by viruses (it is not by chance that the function of the CRISPR system was identified in industrial settings). Substantiating the role of CTP, natural selection has dealt with this hurdle via synthesis of the antimetabolite 30-deoxy-30,40-didehydro- CTP, recruited for antiviral immunity in all domains of life. (shrink)

Engineered microbes are of great potential utility in biotechnology and basic research. In principle, a cell can be built from scratch by assembling small molecule sets with auto‐catalytic properties. Alternatively, DNA can be isolated or directly synthesized and molded into a synthetic genome using existing genomic blueprints and molecular biology tools. Activating such a synthetic genome will yield a synthetic cell. Here we examine obstacles associated with this latter approach using a model system whereby a donor genome (...) from H. influenzae is fragmented, and the pieces are then modified and reassembled stepwise in an E. coli host cell. There are obstacles associated with this strategy related to DNA transfer, DNA replication, cross‐talk in gene regulation and compatibility of gene products between donor and host. Encouragingly, analysis of gene expression indicates widespread transcription of H. influenzae genes in E. coli, and analysis of gap locations in H. influenzae and other microbial genome assemblies reveals few genes routinely incompatible with E. coli. In conclusion, rebuilding and booting a genome remains a feasible and pragmatic approach to creating a synthetic microbial cell. BioEssays 29:580–590, 2007. © 2007 Wiley Periodicals, Inc. (shrink)

In recent years, the publication of the studies on the transmissibility in mammals of the H5N1 influenza virus and synthetic genomes has triggered heated and concerned debate within the community of scientists on biological dual-use research; these papers have raised the awareness that, in some cases, fundamental research could be directed to harmful experiments, with the purpose of developing a weapon that could be used by a bioterrorist. Here is presented an overview regarding the dual-use concept and its related (...) international agreements which underlines the work of the Australia Group Export Control Regime. It is hoped that the principles and activities of the AG, that focuses on export control of chemical and biological dual-use materials, will spread and become well known to academic researchers in different countries, as they exchange biological materials and scientific papers. To this extent, and with the aim of drawing the attention of the scientific community that works with yeast to the so called Dual-Use Research of Concern, this article reports case studies on biological dual-use research and discusses a synthetic biology applied to the yeast Saccharomyces cerevisiae, namely the construction of the first eukaryotic synthetic chromosome of yeast and the use of yeast cells as a factory to produce opiates. Since this organism is considered harmless and is not included in any list of biological agents, yeast researchers should take simple actions in the future to avoid the sharing of strains and advanced technology with suspicious individuals. (shrink)

Metaphors allow us to come to terms with abstract and complex information, by comparing it to something which is structured, familiar and concrete. Although modern science is “iconoclastic”, as Gaston Bachelard phrases it, scientists are at the same time prolific producers of metaphoric images themselves. Synthetic biology is an outstanding example of a technoscientific discourse replete with metaphors, including textual metaphors such as the “Morse code” of life, the “barcode” of life and the “book” of life. This paper focuses (...) on a different type of metaphor, however, namely on the archetypal metaphor of the mandala as a symbol of restored unity and wholeness. Notably, mandala images emerge in textual materials related to one of the new “frontiers” of contemporary technoscience, namely the building of a synthetic cell: a laboratory artefact that functions like a cell and is even able to replicate itself. The mandala symbol suggests that, after living systems have been successfully reduced to the elementary building blocks and barcodes of life, the time has now come to put these fragments together again. We can only claim to understand life, synthetic cell experts argue, if we are able to technically reproduce a fully functioning cell. This holistic turn towards the cell as a meaningful whole also requires convergence at the “subject pole”: the building of a synthetic cell as a practice of the self, representing a turn towards integration, of multiple perspectives and various forms of expertise. (shrink)

To construct a synthetic cell we need to understand the rules that permit life. A central idea in modern biology is that in addition to the four entities making reality, matter, energy, space and time, a fifth one, information, plays a central role. As a consequence of this central importance of the management of information, the bacterial cell is organised as a Turing machine, where the machine, with its compartments defining an inside and an outside and its metabolism, reads (...) and expresses the genetic program carried by the genome. This highly abstract organisation is implemented using concrete objects and dynamics, and this is at the cost of repeated incompatibilities (frustration), which need to be sorted out by appropriate «patches». After describing the organisation of the genome into the paleome (sustaining and propagating life) and the cenome (permitting life in context), we describe some chemical hurdles that the cell as to cope with, ending with the specific case of the methionine salvage pathway. (shrink)

One of the most active areas of research in semi-supervised learning has been to study methods for constructing good ensembles of classifiers. Ensemble systems are techniques that create multiple models and then combine them to produce improved results. These systems usually produce more accurate solutions than a single model would. Specially, multi-view ensemble systems improve the accuracy of text classification because they optimize the functions to exploit different views of the same input data. However, despite being more promising than the (...) single-view approaches, document datasets often have no natural multiple views available. This study proposes an algorithm to generate a synthetic view from a standard text dataset. The model generates a new view from the standard bag-of-words approach using an algorithm based on hidden Markov models. To show the effectiveness of the proposed HMM-based synthetic view generation method, it has been integrated in a co-training ensemble system and tested with four text corpora: Reuters, 20 Newsgroup, TREC Genomics and OHSUMED. The results obtained are promising, showing a significant increase in the efficiency of the ensemble system compared to a single-view approach. (shrink)

Recent sequencing of the metazoan Oikopleura dioica genome has provided important insights, which challenges the current understanding of eukaryotic genome evolution. Many genomic features of O. dioica show deviation from the commonly observed trends in other eukaryotic genomes. For instance, O. dioica has a rapidly evolving, highly compact genome with a divergent intron‐exon organization. Additionally, O. dioica lacks the minor spliceosome and key DNA repair pathway genes. Even with a compact genome, O. dioica contains tandem repeats, comparable to other eukaryotes, (...) and shows lineage‐specific expansion of certain protein domains. Here, we review its genomic features in the context of current knowledge, discuss implications for contemporary biology and identify areas for further research. Analysis of the O. dioica genome suggests that non‐adaptive forces such as elevated mutation rates might influence the evolution of genome architecture. The knowledge of unique genomic features and splicing mechanisms in O. dioica may be exploited for synthetic biology applications, such as generation of orthogonal splicing systems. (shrink)

Synthetic biology (synbio) involves designing and creating new living systems to serve human ends, using techniques including molecular biology, genomics, and engineering. Existing bioethical analyses of synbio focus largely on balancing benefits against harms, the dual-use dilemma, and metaphysical questions about creating and commercializing synthetic organisms. We argue that these approaches fail to consider key feminist concerns. We ground our normative claims in two case studies, focusing on the public good, who holds and wields power, and synbio (...) research projects’ particularity and context. Attention to feminist concerns is essential for synbio to realize its potential in ethically justifiable ways. (shrink)

This paper links two domains of recent interest in science and technology studies, complexity and ignorance, in the context of knowledge practices observed among synthetic biologists. Synthetic biologists are recruiting concepts and methods from computer science and electrical engineering in order to design and construct novel organisms in the lab. Their field has taken shape amidst revised assessments of life’s complexity in the aftermath of the Human Genome Project. While this complexity is commonly taken to be an immanent (...) property of biological systems, this article presents an epistemological view of complexity according to which complexity relates to a specific scientific theory or model and refers to that which exceeds the theory or model’s explanatory power. This epistemological view allows us to narrate a particular story about the changing relationship between biology and synthetic biology in the last decade and accounts for early knowledge practices in synthetic biology that “ignored” biology. This article further argues that while the failure of ignorance to produce clear-cut results for synthetic biologists has led practitioners back to biology, the entanglements between different pragmatic orientations and ways of knowing trouble the implications of this return for assessments of the complexity of biological systems. (shrink)

Emergence of novel genome engineering technologies such as clustered regularly interspaced short palindromic repeat has refocused attention on unresolved ethical complications of synthetic biology. Biosecurity concerns, deontological issues and human right aspects of genome editing have been the subject of in-depth debate; however, a lack of transparent regulatory guidelines, outdated governance codes, inefficient time-consuming clinical trial pathways and frequent misunderstanding of the scientific potential of cutting-edge technologies have created substantial obstacles to translational research in this area. While a precautionary (...) principle should be applied at all stages of genome engineering research, the stigma of germline editing, synthesis of new life forms and unrealistic presentation of current technologies should not arrest the transition of new therapeutic, diagnostic or preventive tools from research to clinic. We provide a brief review on the present regulation of CRISPR and discuss the translational aspect of genome engineering research and patient autonomy with respect to the “right to try” potential novel non-germline gene therapies. (shrink)

Synthetic Biology and Renewal of the Ethics of the Research. From the Genome Editing to Organoids of the Brains In this paper I will address the philosophical and scientific impact brought up by “synthetic biology” from the beginning of embryogeny to the fabrication of organoids, to analyze how this paradigm shift impacts on our definition of what a good life is, or should be, in rehabilitation a dialog between sciences and philosophy.

This article opens with a disclaimer: I am not a scientist, and the science of synthetic biology is beyond my comprehension. I am a philosopher and an ethicist interested in moral issues in reproductive medicine. In my past research I have raised theoretical questions about the normative constraints on the creation of human beings, especially in the context of the debates on genetic screening and genetic engineering, on both the individual level and the collective, namely that pertaining to the (...) intervention in the human genome.Moral norms usually apply to our relations with other human beings. The questions of reproductive medicine are problematic, since although they relate to human beings, these human beings are .. (shrink)

The Human Genome Project is nearing completion, and shortly we will have access to the complete genetic sequence of an average human being. Hopes are high that the sequence will contribute profoundly to medicine in particular, but also to our understanding of our evolutionary past. Of course, detractors have long insisted that because the HGP represents a victory for formalism in biology, determining the function of DNA sequences will remain an outstanding problem for at least the next several decades. Moreover, (...) it is not clear that having the complete sequence will be significantly useful to biologists seeking to understand gene function in the first place. What can we expect in the postgenomic era? ;I reject the very idea that a complete, encapsulated sequence of a human genome is foundational to biological understanding. I set my investigation within the framework of the ancient debate between preformationists and epigenecists. I survey and conceptually analyze arguments on both sides, especially as they relate to the separation of genetics and embryology in the early part of the twentieth century. I identify modern variants of both preformationism and epigenesis, and note their reconciliation in the form of a Modern Consensus on development established after the neo-Darwinian Synthesis in biology in the 1940s. ;Drawing on recent work in molecular and developmental biology, I challenge the seeming intuitiveness of the Modern Consensus and its subsumption of developmental concerns under the aegis of molecular genetics. I then propose and defend an alternative synthesis of preformationism and epigenesis, and of genetics and developmental biology, according to which development does not reduce to mere gene activation. I underscore the practical benefit of my perspective through a lengthy discussion of the psychiatric genetics approach to schizophrenia. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Kennedy Institute of Ethics Journal 14.1 (2004) 47-54 [Access article in PDF] Ethical Guidelines for Human Embryonic Stem Cell Research*(A Recommended Manuscript) Adopted on 16 October 2001Revised on 20 August 2002 Ethics Committee of the Chinese National Human Genome Center at Shanghai, Shanghai 201203 Human embryonic stem cell (ES) research is a great project in the frontier of biomedical science for the twenty-first century. Be- cause the research involves (...) the use of human embryos, it triggers serious debate on ethical issues. Opponents consider the embryo to be an early form of human life that should be respected and not destroyed. However, the majority of scientists support embryonic stem cell research, believing that it offers good prospects for the treatment of diseases that have remained incurable until now and so will benefit humankind. The Ethics Committee of the Department of Ethical, Legal, and Social Implications of the Chinese National Human Genome Center at Shanghai seriously discussed the ethical debate initiated by embryonic stem cell research. We concluded that we should support the scientists of our country in actively carrying out human embryonic stem cell research for the noble cause of "medicine being a beneficent art." For the healthy and orderly development of human embryonic stem cell research in our country, we put forward the following recommended Ethical Guidelines for Human Embryonic Stem Cell Research as a reference for leaders, administrative departments, and related scientists. Preface Article 1. Human embryonic stem cells are the primitive cells that play the main role in the growth and development of a human body. These [End Page 47] primitive cells have the potential for infinite proliferation, self-renewal, and multi-directional differentiation. If scientists can discover the mechanism of differentiation of human embryonic stem cells, it will be possible to induce differentiation of human embryonic stem cells to form various types of human cells for clinical cell therapy. If human embryonic stem cell research can be integrated with modern biomedical engineering techniques, it also will be possible to make repair and replacement of human tissues and organs a reality. Article 2. There are two ways to classify human embryonic stem cells. One way is to classify them according to their potential for differentiation. There could be three kinds of stem cells: totipotent stem cells, pluripotent stem cells, and unipotent stem cells.A totipotent stem cell has the potential to develop into a whole individual. It can differentiate into the more than 200 cell types in the whole body, construct any tissue or organ of the body, and finally develop into a whole individual. The fertilized egg and the cleavage cells at the very early stage of embryonic development are totipotent stem cells.A pluripotent stem cell has the potential to differentiate into many cell types derived from the three embryonic layers. However, it has lost the capacity to develop into a complete organism.A unipotent stem cell is derived from the further differentiation of the pluripotent stem cell. It can differentiate only into one cell type such as a hematopoietic stem cell, neural stem cell, and others.The other way is to classify human stem cells according to their source. There could be two kinds of human stem cells: embryonic stem cells and tissue stem cells (also called adult stem cells). The former involves experimentation with embryos, which has serious ethical implications. Ethical issues associated with the latter are mainly expressed in the various opinions regarding the allocation of health resources. Article 3. Human embryonic stem cells are the group of cells called the blastocyst inner cell mass during the early stage of embryonic development. They are the main source of totipotent stem cells, and hence the focal and hot point in stem cell research. Studies on the clinical application of embryonic stem cells probably will involve use of the somatic cell nucleus transfer (SCNT) technique, which destroys the early human embryo. At present, the ethical and moral debate is very serious in human embryonic stem cell research regarding whether the research will develop... (shrink)

A team of US researchers recently reported the design, assembly and in vivo functionality of a synthetic chromosome III (SynIII) for the yeast Saccharomyces cerevisiae. The synthetic chromosome was assembled bottom‐up from DNA oligomers by teams of students working over several years with researchers as the first part of an international synthetic yeast genome project. Embedded into the sequence of the synthetic chromosome are multiple design changes that include a novel in‐built recombination scheme that can be (...) induced to catalyse intra‐chromosomal rearrangements in a variety of different conditions. This system, along with the other synthetic sequence changes, is intended to aid researchers develop a deeper understanding of how genomes function and find new ways to exploit yeast in future biotechnologies. The landmark of the first synthesised designer eukaryote chromosome, and the power of its massively parallel recombination system, provide new perspectives on the future of synthetic biology and genome research. (shrink)

Cancer drugs are broadly classified into two categories: cytotoxic chemotherapies and targeted therapies that specifically modulate the activity of one or more proteins involved in cancer. Major advances have been achieved in targeted cancer therapies in the past few decades, which is ascribed to the increasing understanding of molecular mechanisms for cancer initiation and progression. Consequently, monoclonal antibodies and small molecules have been developed to interfere with a specific molecular oncogenic target. Targeting gain‐of‐function mutations, in general, has been productive. However, (...) it has been a major challenge to use standard pharmacologic approaches to target loss‐of‐function mutations of tumor suppressor genes. Novel approaches, including synthetic lethality and collateral vulnerability screens, are now being developed to target gene defects in p53, PTEN, and BRCA1/2. Here, we review and summarize the recent findings in cancer genomics, drug development, and molecular cancer biology, which show promise in targeting tumor suppressors in cancer therapeutics. (shrink)

The first promising results from “streamlined,” minimal genomes tend to support the notion that these are a useful tool in biological systems engineering. However, compared with the speed with which genomic microbial sequencing has provided us with a wealth of data to study biological functions, it is a slow process. So far only a few projects have emerged whose synthetic ambition even remotely matches our analytic capabilities. Here, we survey current technologies converging into a future ability to engineer large‐scale (...) biological systems. We argue that the underlying synthetic technology, de novo DNA synthesis, is already rather mature – in particular relative to the scope of our current synthetic ambitions. Furthermore, technologies towards rationalizing the design of the newly synthesized DNA fragment are emerging. These include techniques to implement complex regulatory circuits, suites of parts on a DNA and RNA level to fine tune gene expression, and supporting computational tools. As such DNA fragments will, in most cases, be destined for operating in a cellular context, attention has to be paid to the potential interactions of the host with the functions encoded on the engineered DNA fragment. Here, the need of biological systems engineering to deal with a robust and predictable bacterial host coincides with current scientific efforts to theoretically and experimentally explore minimal bacterial genomes. (shrink)

In 2010, the Venter lab announced that it had created the first bacterium with an entirely synthetic genome. This was reported to be the first instance of ‘artificial life,’ and in the ethical and policy discussions that followed it was widely assumed that the creation of artificial life is in itself morally significant. We cast doubt on this assumption. First we offer an account of the creation of artificial life that distinguishes this from the derivation of organisms from existing (...) life and clarify what we mean in asking whether the creation of artificial life has moral significance. We then articulate and evaluate three attempts to establish that the creation of artificial life is morally significant. These appeal to the claim that the creation of artificial life involves playing God, as expressed in three distinct formulations; the claim that the creation of artificial life will encourage reductionist attitudes toward the living world that undermine the special moral value accorded to life; and the worry that artificial organisms will have an uncertain functional status and consequently an uncertain moral status. We argue that all three attempts to ground the moral significance of the creation of artificial life fail, because none of them establishes that the creation of artificial life is morally problematic in a way that the derivation of organisms from existing life forms is not. We conclude that the decisive moral consideration is not how life is created but what non-genealogical properties it possesses. (shrink)

Technology shapes every aspect of human experience and it is the primary driver of social and ecological change. Given this, it is surprising that we spend so little time studying, analyzing, and evaluating new technologies. Occasionally, an issue grabs public attention--for example, the use of human embryonic stem cells in medical research or online file sharing of music and movies. However, these are the exceptions. For the most part, we enthusiastically embrace each new technology and application with little critical reflection (...) on how it will impact our lives and our world. What is more, when an issue raised by an emerging technology is attended to, we often lack the language, concepts, and critical perspectives to thoroughly address it. The aim of this textbook is to introduce students and other readers to the ethical issues associated with a broad array of emerging technologies--including nanotechnology, synthetic genomics, robotics, genetic engineering, geoengineering, synthetic meat, virtual reality, information technologies, sex selection, and many more--and to help them develop analytical skills and perspectives for effectively evaluating novel technologies and applications. (shrink)

Fundamental questions in evolution concern deep divisions in the living world and vertical versus horizontal information transfer. Two contrasting views are: (i) three superkingdoms Archaea, Eubacteria, and Eukarya based on vertical inheritance of genes encoding ribosomes; versus (ii) a prokaryotic/eukaryotic dichotomy with unconstrained horizontal gene transfer (HGT) among prokaryotes. Vertical inheritance implies continuity of cytoplasmic and structural information whereas HGT transfers only DNA. By hypothesis, HGT of the translation machinery is constrained by interaction between new ribosomal gene products and vertically (...) inherited cytoplasmic structure made largely of preexisting ribosomes. Ribosomes differentially enhance the assembly of new ribosomes made from closely related genes and inhibit the assembly of products from more distal genes. This hypothesis suggests experiments for synthetic biology: the ability of synthetic genomes to “boot,” i.e., establish hereditary continuity, will be constrained by the phylogenetic closeness of the cell “body” into which genomes are placed. (shrink)

Inspired by the success of synthesising organic substances by Friedrich Wöhler in 1828, the vision of creating life in the laboratory synthetically has become increasingly accessible for today’s synthetic biology and synthetic genomics, respectively. The engineering of biology – a contemporary version of the liaison of technology and organic form – creates cellular machines, biobricks, biomolecular ‘borgs’, and entire synthetic genomes of artificial organisms. Besides major ethical concerns, the shift in scientific epistemology is of interest. Unlike (...) classical analytical science, synthetic science understands by a process of generation, through which myriads of new things are created, dramatically changing the living environment. (shrink)

Synthetic biologists design and engineer organisms for a better and more sustainable future. While the manifold prospects are encouraging, concerns about the uncertain risks of genome editing affect public opinion as well as local regulations. As a consequence, biosafety and associated concepts, such as the Safe-by-design framework and genetic safeguard technologies, have gained notoriety and occupy a central position in the conversation about genetically modified organisms. Yet, as regulatory interest and academic research in genetic safeguard technologies advance, the implementation (...) in industrial biotechnology, a sector that is already employing engineered microorganisms, lags behind. The main goal of this work is to explore the utilization of genetic safeguard technologies for designing biosafety in industrial biotechnology. Based on our results, we posit that biosafety is a case of a changing value, by means of further specification of how to realize biosafety. Our investigation is inspired by the Value Sensitive Design framework, to investigate scientific and technological choices in their appropriate social context. Our findings discuss stakeholder norms for biosafety, reasonings about genetic safeguards, and how these impact the practice of designing for biosafety. We show that tensions between stakeholders occur at the level of norms, and that prior stakeholder alignment is crucial for value specification to happen in practice. Finally, we elaborate in different reasonings about genetic safeguards for biosafety and conclude that, in absence of a common multi-stakeholder effort, the differences in informal biosafety norms and the disparity in biosafety thinking could end up leading to design requirements for compliance instead of for safety. (shrink)

[ENGLISH] This article discusses the potential of synthetic biology to address fundamental questions in the philosophy of biology regarding the nature of life and biological functions. Synthetic biology aims to reduce living organisms to their simplest forms by identifying the minimal components of a cell and also to create novel life forms through genetic reprogramming, biobrick assembly, or novel proteins. However, the technical success of these endeavors does not guarantee their conceptual success in defining life. There is a (...) lack of consensus among researchers on how to define and classify the entities produced in the lab, whether they should be considered living or categorized differently. The criteria for minimal cells and minimal life are subject to arbitrary choices and varying interpretations. The concept of function, crucial to synthetic biology, is also difficult to define. The article highlights the need to consider the minimal set of functions that characterize life before determining the smallest genomes that code for those functions. The arbitrary nature of defining both life and function complicates the understanding and classification of these entities. The article suggests that the traditional dichotomy between the living and the non-living may no longer be valid and that the concept of life itself may not require precise scientific definition. As synthetic biology advances, the article emphasizes the importance of redefining or constructing new categories to encompass the expanding possibilities and creations in the field. The ability to create new life forms raises questions about recognition, identification, and ethical implications, requiring a conceptual and philosophical engagement beyond the technical achievements of synthetic biology. -/- [FRENCH] L'article aborde le potentiel de la biologie synthétique pour répondre à des questions fondamentales de la philosophie de la biologie concernant la nature de la vie et des fonctions biologiques. La biologie synthétique vise à réduire les organismes vivants à leurs formes les plus simples en identifiant les composants minimaux d'une cellule et à créer de nouvelles formes de vie grâce à la reprogrammation génétique, à l'assemblage de biobriques ou à des protéines nouvelles. Cependant, le succès technique de ces approches ne garantit pas leur réussite conceptuelle dans la définition de la vie. Il n'y a pas de consensus parmi les chercheurs sur la façon de définir et de classer les entités produites en laboratoire, qu'elles doivent être considérées comme vivantes ou catégorisées différemment. Les critères des cellules minimales et de la vie minimale sont soumis à des choix arbitraires et à des interprétations variables. La notion de fonction, essentielle en biologie synthétique, est également difficile à définir. L'article met en évidence la nécessité de prendre en compte l'ensemble minimal de fonctions qui caractérisent la vie avant de déterminer les plus petits génomes qui codent ces fonctions. La nature arbitraire de la définition de la vie et de la fonction complique la compréhension et la classification de ces entités. L'article suggère que la dichotomie traditionnelle entre le vivant et le non-vivant pourrait ne plus être valable et que le concept même de vie ne nécessite pas une définition scientifique précise. À mesure que la biologie synthétique progresse, l'article souligne l'importance de redéfinir ou de construire de nouvelles catégories pour englober les possibilités et créations croissantes dans le domaine. La capacité à créer de nouvelles formes de vie soulève des questions de reconnaissance, d'identification et d'implications éthiques, nécessitant une réflexion conceptuelle et philosophique au-delà des avancées techniques de la biologie synthétique. (shrink)

The development of synthetic biology calls for accurate understanding of the critical functions that allow construction and operation of a living cell. Besides coding for ubiquitous structures, minimal genomes encode a wealth of functions that dissipate energy in an unanticipated way. Analysis of these functions shows that they are meant to manage information under conditions when discrimination of substrates in a noisy background is preferred over a simple recognition process. We show here that many of these functions, including transporters (...) and the ribosome construction machinery, behave as would behave a material implementation of the informationmanaging agent theorized by Maxwell almost 150 years ago and commonly known as Maxwell’s demon (MxD). A core gene set encoding these functions belongs to the minimal genome required to allow the construction of an autonomous cell. These MxDs allow the cell to perform computations in an energy-efficient way that is vastly better than our contemporary computers. (shrink)

The first IVF baby was born in the 1970s. Less than 20 years later, we had cloning and GM food, and information and communication technologies had transformed everyday life. In 2000, the human genome was sequenced. More recently, there has been much discussion of the economic and social benefits of nanotechnology, and synthetic biology has also been generating controversy. This important volume is a timely contribution to increasing calls for regulation - or better regulation - of these and other (...) new technologies. Drawing on an international team of legal scholars, it reviews and develops the role of human rights in the regulation of new technologies. Three controversies at the intersection between human rights and new technology are given particular attention. First, how the expansive application of human rights could contribute to the creation of a brave new world of choice, where human dignity is fundamentally compromised; second, how new technologies, and our regulatory responses to them, could be a threat to human rights; and, third, how human rights could be used to create better regulation of these technologies. (shrink)

Get the science facts, not science fiction, on the cutting-edge developments that are already changing the course of our future. Every day, scientists conduct pioneering experiments with the potential to transform how we live. Yet it isn’t every day you hear from the scientists themselves! Now, award–winning author Jim Al–Khalili and his team of top-notch experts explain how today’s earthshaking discoveries will shape our world tomorrow—and beyond. Pull back the curtain on: genomics robotics AI the “Internet of Things” (...) class='Hi'>synthetic biology transhumanism interstellar travel colonization of the solar system teleportation and much more And find insight into big–picture questions such as: Will we find a cure to all diseases? The answer to climate change? And will bionics one day turn us into superheroes? The scientists in these pages are interested only in the truth—reality-based and speculation-free. The future they conjure is by turns tantalizing and sobering: There’s plenty to look forward to, but also plenty to dread. And undoubtedly the best way to for us to face tomorrow’s greatest challenges is to learn what the future looks like—today. Praise for What the Future Looks Like “A collection of mind-boggling essays that are just the thing for firing up your brain cells.” —Saga Magazine “The predictions and impacts are global... [and] the book contains far more fascinating information than can be covered in this review.” —Choice “This book is filled with essays from experts offering their informed opinions on what the science and technology of today will look like in the future, from smart materials to artificial intelligence to genetic editing.” —Popular Science “Fun is an understatement. This is a great collection to get the summer book season started.” —Forbes.com “The focus on sincere, factual presentation of current and future possibilities by leading experts is particularly welcome in this era of fake news and anti-science rhetoric.” —Library Journal. (shrink)

The key objective of this volume is to allow philosophy students and early-stage researchers to become practicing philosophers in technoscientific settings. Zwart focuses on the methodological issue of how to practice continental philosophy of technoscience today. This text draws upon continental authors such as Hegel, Engels, Heidegger, Bachelard and Lacan in developing a coherent message around the technicity of science or rather, “technoscience”. Within technoscience, the focus will be on recent developments in life sciences research, such as genomics, post- (...) class='Hi'>genomics, synthetic biology and global ecology. This book uniquely presents continental perspectives that tend to be underrepresented in mainstream philosophy of science, yet entail crucial insights for coming to terms with technoscience as it is evolving on a global scale today. This is an open access book. (shrink)

Recent analysis of genome sequences has identified individuals that are healthy despite carrying severe disease‐associated mutations. A possible explanation is that these individuals carry a second genomic perturbation that can compensate for the detrimental effects of the disease allele, a phenomenon referred to as suppression. In model organisms, suppression interactions are generally divided into two classes: genomic suppressors which are secondary mutations in the genome that bypass a mutant phenotype, and dosage suppression interactions in which overexpression of a suppressor gene (...) rescues a mutant phenotype. Here, we describe the general properties of genomic and dosage suppression, with an emphasis on the budding yeast. We propose that suppression interactions between genetic variants are likely relevant for determining the penetrance of human traits. Consequently, an understanding of suppression mechanisms may guide the discovery of protective variants in healthy individuals that carry disease alleles, which could direct the rational design of new therapeutics. (shrink)

The title of Beth Shapiro’s ‘How to Clone a Mammoth’ contains an implicature: it suggests that it is indeed possible to clone a mammoth, to bring extinct species back from the dead. But in fact Shapiro both denies this is possible, and denies there would be good reason to do it even if it were possible. The de-extinct ‘mammoths’ she speaks of are merely ecological proxies for mammoths—elephants re-engineered for cold-tolerance by the addition to their genomes of a few mammoth (...) genes. Shapiro’s denial that genuine species de-extinction is possible is based on her assumption that resurrected organisms would need to be perfectly indistinguishable from the creatures that died out. In this article I use the example of an extinct New Zealand wattlebird, the huia, to argue—contra Shapiro—that there are compelling reasons to resurrect certain species if it can be done. I then argue—again, contra Shapiro—that synthetically created organisms needn’t be perfectly indistinguishable from their genetic forebears in order for species de-extinction to be successful. (shrink)

Systems biology is the rapidly growing and heavily funded successor science to genomics. Its mission is to integrate extensive bodies of molecular data into a detailed mathematical understanding of all life processes, with an ultimate view to their prediction and control. Despite its high profile and widespread practice, there has so far been almost no bioethical attention paid to systems biology and its potential social consequences. We outline some of systems biology's most important socioethical issues by contrasting the concept (...) of systems as dynamic processes against the common static interpretation of genomes. New issues arise around systems biology's capacities for in silico testing, changing cultural understandings of life, synthetic biology, and commercialization. We advocate an interdisciplinary and interactive approach that integrates social and philosophical analysis and engages closely with the science. Overall, we argue that systems biology socioethics could stimulate new ways of thinking about socioethical studies of life sciences. (shrink)