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)

Data-sharing among genomic researchers is promoted for its potential to accelerate our understanding of the molecular basis of cancer. However, with genomic data sharing the risks of re-identifying study participants, revealing personal genomic information and data misuse might increase. This study aims at exploring perceptions of patients and physicians in Oncology regarding their assessment of the informational risks resulting from participating in whole genomic research studies in order to improve the informed consent process. For this purpose, we conducted a qualitative (...) focus group study at the National Center for Tumor Diseases (NCT). Patients and oncologists assessed the informational risks either as minimal or as greater than minimal, depending on the context factors of occupational status, age, and patients’ prognosis. Interestingly, even patients who assumed a greater risk did not refrain from participating in genomic research, provided that certain informational and institutional safeguards are implemented. Moreover, they expected comprehensive disclosure of the risks resulting from genomic data sharing. These results suggest (1) comprehensive disclosure of the risks of genomic research to potential study participants in genomic research to facilitate risk assessment and sound decision making, (2) establishing independent governance entities in order to minimize the informational risks of genomic research, and (3) implementing data sharing policies which offer guidance for physicians and researchers involved in genomic research. (shrink)

Data-sharing among genomic researchers is promoted for its potential to accelerate our understanding of the molecular basis of cancer. However, with genomic data sharing the risks of re-identifying study participants, revealing personal genomic information and data misuse might increase. This study aims at exploring perceptions of patients and physicians in Oncology regarding their assessment of the informational risks resulting from participating in whole genomic research studies in order to improve the informed consent process. For this purpose, we conducted a qualitative (...) focus group study at the National Center for Tumor Diseases. Patients and oncologists assessed the informational risks either as minimal or as greater than minimal, depending on the context factors of occupational status, age, and patients’ prognosis. Interestingly, even patients who assumed a greater risk did not refrain from participating in genomic research, provided that certain informational and institutional safeguards are implemented. Moreover, they expected comprehensive disclosure of the risks resulting from genomic data sharing. These results suggest comprehensive disclosure of the risks of genomic research to potential study participants in genomic research to facilitate risk assessment and sound decision making, establishing independent governance entities in order to minimize the informational risks of genomic research, and implementing data sharing policies which offer guidance for physicians and researchers involved in genomic research. (shrink)

Prokaryotic genomes of endosymbionts and parasites are examples of naturally evolved minimal cells, the study of which can shed light on life in its minimum form. Their diverse biology, their lack of a large set of orthologous genes and the existence of essential linage (and environmentally) specific genes all illustrate the diversity of genes building up naturally evolved minimal cells. This conclusion is reinforced by the fact that sometimes the same essential function is performed by genes from different (...) evolutionary origins. Nevertheless, all cells perform a set of life‐essential functions however different their cell machinery and environment in which they thrive. An upcoming challenge for biologists will be to discern, by studying differences and similarities in current biodiversity, how cells with reduced genomes have adapted while retaining all basic life‐supporting functions. (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)

Genomic instability is a hallmark of cancer. Cancer cells that exhibit abnormal chromosomes are characteristic of most advanced tumours, despite the potential threat represented by accumulated genetic damage. Carcinogenesis involves a loss of key components of the genetic and signalling molecular networks; hence some authors have suggested that this is part of a trend of cancer cells to behave as simple, minimal replicators. In this study, we explore this conjecture and suggest that, in the case of cancer, genomic instability (...) has an upper limit that is associated with a minimal cancer cell network. Such a network would include (for a given microenvironment) the basic molecular components that allow cells to replicate and respond to selective pressures. However, it would also exhibit internal fragilities that could be exploited by appropriate therapies targeting the DNA repair machinery. The implications of this hypothesis are discussed. (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)

Assisted reproductive technologies have greatly increased our control over reproductive choices, leading some bioethicists to argue that we face unprecedented moral obligations towards progeny. Several models attempting to balance the principle of procreative autonomy with these obligations have been proposed. The least demanding is the minimal threshold model (MTM), according to which every reproductive choice is permissible, except creating children whose lives will not be worth living. Hence, as long as the future child is likely to have a life (...) worth living, prospective parents may be allowed to use preimplantation genetic diagnosis (PGD) to select embryos with genetic diseases or disabilities. Assuming a consequentialist person‐affecting view of morality, this paper investigates whether the MTM is an appropriate tool to guide procreative decisions given the continuous development of reproductive genetic technologies. In particular, I consider germline genome editing (GGE) and I argue that its application in human reproduction, unlike PGD, should be conceived as person‐affecting towards future progeny. I claim that even if we assume the plausibility of the MTM within PGD, we are committed to accepting that a greater moral obligation towards progeny should guide procreative decisions if GGE were available. In this case, the MTM should no longer be considered an appropriate instrument to guide procreative choices. Finally, I investigate when we face this greater moral obligation, concluding that it applies only when prospective parents have already engaged in the in vitro fertilization process. (shrink)

We present a model for genome evolution, comprising biologically plausible events such as transpositions inside the genome and insertions of exogenous sequences. This model attempts to formulate a minimal proposition accounting for key statistical properties of genomes, avoiding, as far as possible, unsupportable hypotheses for the remote evolutionary past. The statistical properties that are observed in genomic sequences and are reproduced by the proposed model are: (i) deviations from randomness at different length scales, measured by suitable algorithms, (...) (ii) a special form of size distribution (power law distribution) characterising different levels of genome organisation in the non‐coding, and (iii) extensive resemblance in the alternation of coding and non‐coding regions at several length scales (self‐similarity) in long genomic sequences of higher eukaryotes. BioEssays 23:647–656, 2001. © 2001 John Wiley & Sons, Inc. (shrink)

Theoretical minimal RNA rings are candidate primordial genes evolved for non‐redundant coding of the genetic code's 22 coding signals (one codon per biogenic amino acid, a start and a stop codon) over the shortest possible length: 29520 22‐nucleotide‐long RNA rings solve this min‐max constraint. Numerous RNA ring properties are reminiscent of natural genes. Here we present analyses showing that all RNA rings lack dinucleotide CG (a mutable, chemically instable dinucleotide coding for Arginine), bearing a resemblance to known CG‐depleted genomes. (...) CG in “incomplete” RNA rings (not coding for all coding signals, with only 3–12 nucleotides) gradually decreases towards CG absence in complete, 22‐nucleotide‐long RNA rings. Presumably, feedback loops during RNA ring growth during evolution (when amino acid assignment fixed the genetic code) assigned Arg to codons lacking CG (AGR) to avoid CG. Hence, as a chemical property of base pairs, CG mutability restructured the genetic code, thereby establishing itself as genetically encoded biological information. (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)

BackgroundA fundamental ethical challenge in conducting genomics research is the question of what and how individual level genetic findings and aggregate genomic results should be conveyed to research participants and communities. This is within the context of minimal guidance, policies, and experiences, particularly in Africa. The aim of this study was to explore the perspectives of key stakeholders' on returning genomics research results to participants in Kenya.MethodsThis qualitative study involved focus group discussions (FGDs) and in-depth interviews (IDIs) with 69 (...) stakeholders. The purposively selected participants, included research ethics committee (REC) members (8), community members (44), community resource persons (8), and researchers (9). A semi-structured interview guide was used to facilitate discussions. Six FGDs and twenty-five (IDIs) were conducted among the different stakeholders. The issues explored in the interviews included: (1) views on returning results, (2) kind of results to be returned, (3) value of returning results to participants, and (4) challenges anticipated in returning results to participants and communities. The interviews were audio-recorded, transcribed verbatim, and coded in Nvivo 12 pro. Thematic and content analysis was conducted.ResultsParticipants agreed on the importance of returning genomic results either as individual or aggregate results. The most cited reasons for returning of genomic results included recognizing participants' contribution to research, encouraging participation in future research, and increasing the awareness of scientific progress. Other aspects on how genomic research results should be shared included sharing easy to understand results in the shortest time possible and maintaining confidentiality when sharing sensitive results.ConclusionsThis study identified key stakeholders’ perspectives on returning genomic results at the individual and community levels in two urban informal settlements of Nairobi. The majority of the participants expect to receive feedback about their genomic results, and it is an obligation for researchers to see how to best fulfil it. (shrink)

We have refined entropy theory to explore the meaning of the increasing sequence data on nucleic acids and proteins more conveniently. The concept of selection constraint was not introduced, only the analyzed sequences themselves were considered. The refined theory serves as a basis for deriving a method to analyze non-coding regions (NCRs) as well as coding regions. Positions with maximal entropy might play the most important role in genome functions as opposed to positions with minimal entropy. This method (...) was tested in the well-characterized coding regions of 12 strains of Classical Swine Fever Virus (CSFV) and non-coding regions of 20 strains of CSFV. It is suitable to analyze nucleic acid sequences of a complete genome and to detect sensitive positions for mutagenesis. As such, the method serves to formulate the basis for elucidating the functional mechanism. (shrink)

The progressive unraveling over the past fifteen years of the structure and function of the human mitochondrial genome, taken as a prototype of all vertebrate mitochondrial genomes, has been marked by a series of startling discoveries. The history of these developments is one in which prediction often turned out to be wrong, and in which solidly established dogmas were violated. The unique features of this genome have forced a revision of our ideas about the universality of the genetic (...) code and of the decoding mechanism, the minimal structural requirements for rRNA, tRNA and mRNA function and the mode and control of gene expression. (shrink)

Against the opinion that DNA as program is not sufficiently explanatory, we maintain that the cellular machinery is entirely computational, and we identify the crucial notion of the interpreter that expresses the gene with the minimal gene set. Epigenetics research does not so much need paradigm shifts as the unraveling of an exceedingly complex computational machine.

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 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)

Entosis, a form of cell cannibalism, is a newly discovered pathogenic mechanism leading to the development of small brains, termed microcephaly, in which P53 activation was found to play a major role. Microcephaly with entosis, found in Pals1 mutant mice, displays P53 activation that promotes entosis and apoptotic cell death. This previously unappreciated pathogenic mechanism represents a novel cellular dynamic in dividing cortical progenitors which is responsible for cell loss. To date, various recent models of microcephaly have bolstered the importance (...) of P53 activation in cell death leading to microcephaly. P53 activation caused by mitotic delay or DNA damage manifests apoptotic cell death which can be suppressed by P53 removal in these animal models. Such genetic studies attest P53 activation as quality control meant to eliminate genomically unfit cells with minimal involvement in the actual function of microcephaly associated genes. In this review, we summarize the known role of P53 activation in a variety of microcephaly models and introduce a novel mechanism wherein entotic cell cannibalism in neural progenitors is triggered by P53 activation. (shrink)

As opposed to a ‘one size fits all’ approach, precision medicine uses relevant biological, medical, behavioural and environmental information about a person to further personalize their healthcare. This could mean better prediction of someone’s disease risk and more effective diagnosis and treatment if they have a condition. Big data allows for far more precision and tailoring than was ever before possible by linking together diverse datasets to reveal hitherto-unknown correlations and causal pathways. But it also raises ethical issues relating to (...) the balancing of interests, viability of anonymization, familial and group implications, as well as genetic discrimination. This article analyses these issues in light of the values of public benefit, justice, harm minimization, transparency, engagement and reflexivity and applies the deliberative balancing approach found in theEthical Framework for Big Data in Health and Research to a case study on clinical genomic data sharing. Please refer to that article for an explanation of how this framework is to be used, including a full explanation of the key values involved and the balancing approach used in the case study at the end. Our discussion is meant to be of use to those involved in the practice as well as governance and oversight of precision medicine to address ethical concerns that arise in a coherent and systematic manner. (shrink)

The placozoan Trichoplax adhaerens is a tiny hairy plate and more simply organized than any other living metazoan. After its original description by F.E. Schulze in 1883, it attracted attention as a potential model for the ancestral state of metazoan organization, the “Urmetazoon”. Trichoplax lacks any kind of symmetry, organs, nerve cells, muscle cells, basal lamina, and extracellular matrix. Furthermore, the placozoan genome is the smallest (not secondarily reduced) genome of all metazoan genomes. It harbors a remarkably rich (...) diversity of genes and has been considered the best living surrogate for a metazoan ancestor genome. The phylum Placozoa presently harbors three formally described species, while several dozen “cryptic” species are yet awaiting their description. The phylogenetic position of placozoans has recently become a contested arena for modern phylogenetic analyses and view‐driven claims. Trichoplax offers unique prospects for understanding the minimal requirements of metazoan animal organization and their corresponding malfunctions. (shrink)

The science of genetics is undergoing a paradigm shift. Recent discoveries, including the activity of retrotransposons, the extent of copy number variations, somatic and chromosomal mosaicism, and the nature of the epigenome as a regulator of DNA expressivity, are challenging a series of dogmas concerning the nature of the genome and the relationship between genotype and phenotype. According to three widely held dogmas, DNA is the unchanging template of heredity, is identical in all the cells and tissues of the (...) body, and is the sole agent of inheritance. Rather than being an unchanging template, DNA appears subject to a good deal of environmentally induced change. Instead of identical DNA in all the cells of the body, somatic mosaicism appears to be the normal human condition. And DNA can no longer be considered the sole agent of inheritance. We now know that the epigenome, which regulates gene expressivity, can be inherited via the germline. These developments are particularly significant for behavior genetics for at least three reasons: First, epigenetic regulation, DNA variability, and somatic mosaicism appear to be particularly prevalent in the human brain and probably are involved in much of human behavior; second, they have important implications for the validity of heritability and gene association studies, the methodologies that largely define the discipline of behavior genetics; and third, they appear to play a critical role in development during the perinatal period and, in particular, in enabling phenotypic plasticity in offspring. I examine one of the central claims to emerge from the use of heritability studies in the behavioral sciences, the principle of minimal shared maternal effects, in light of the growing awareness that the maternal perinatal environment is a critical venue for the exercise of adaptive phenotypic plasticity. This consideration has important implications for both developmental and evolutionary biology. (shrink)

Constructivist biosemiotics foundations imply the first-person basis of cognition. CBF are developed by the biology of cognition, relational biology, enactive approach, ecology of mind, second order cybernetics, genetic epistemology, gestalt, ecological perception and affordances, and active inference by minimization of free energy. CBF reject the idea of an objective independent reality to be represented by information processing in order to be the fittest. CBF assumes that perception is the behavioral configuration of an object and objects are tokens for eigen-behaviors. Cognition (...) takes place in the organism-environment structural coupling during the ontogeny and phylogeny of all biological unities including unicellular organisms. Therefore, if exogenous DNA particles are just tokens for the cell signalling eigen-behaviors, if there is no ‘information’ in the DNA sequence, how can we explain that the same virus or trans- sequence is associated with a similar phenotype? We call this ‘exogenomic problem’. With this basic example, but sufficiently generic to the whole biological world, we agree respectively with Autopoiesis, -system, and Gaia theory: i) ‘Information, code and meaning’ in the DNA sequence belong to the domain of the observer’s description. ii) Genetic ‘information’ is not a program or algorithmic software in DNA sequence. Rather it is a microphysical observable mode of eigen-behaviors in biological unities. iii) The transfer and acquisition of DNA particles is a biospheric phenomenon that maintains its homeorhesis, symbiotic and biosemiotic entailment. Based on the theoretical and experimental results of these theories, it is concluded that genetic ‘information’ is not a genomic sequence, nor any kind of information, but for the cell DNA must embody physical forcing. Genetic characters are the effects and not the cause of phenotype and DNA particles do not ‘use or manipulate’ cellular metabolism. Rather, any cellular configuration change that occurred before or during DNA perturbation is determined on the basis of the cellular standpoint. (shrink)

It is argued that multiscale approaches are necessary for an explanatory modeling of biological systems. A first step, besides common to the multiscale modeling of physical and living systems, is a bottom-up integration based on the notions of effective parameters and minimal models. Top-down effects can be accounted for in terms of effective constraints and inputs. Biological systems are essentially characterized by an entanglement of bottom-up and top-down influences following from their evolutionary history. A self-consistent multiscale scheme is proposed (...) to capture the ensuing circular causality. Its differences with standard mean-field self-consistent equations and slow-fast decompositions are discussed. As such, this scheme offers a way to unravel the multilevel architecture of living systems and their regulation. Two examples, genome functions and biofilms, are detailed. (shrink)

Background There is growing consensus in favor of returning individual specific research results that are clinically actionable, valid, and reliable. However, deciding what and how research results should be returned remains a challenge. Researchers are key stakeholders in return of results decision-making and implementation. Multi-omics data contains medically relevant findings that could be considered for return. We sought to understand researchers' views regarding the potential for return of results for multi-omics data from a large, national consortium generating multi-omics data. Methods (...) Researchers from the Molecular Transducers of Physical Activity Consortium (MoTrPAC) were recruited for in-depth semi-structured interviews. To assess understanding of potential clinical utility for types of data collected and attitudes towards return of results in multi-omic clinical studies, we devised an interview guide focusing on types of results generated in the study for hypothetical return based on review of the literature and professional expertise of team members. The semi-structured interviews were recorded, transcribed verbatim and co-coded. Thematic trends were identified for reporting. Results We interviewed a total of 16 individuals representative of 11 sites and 6 research roles across MoTrPAC. Many respondents expressed positive attitudes regarding hypothetical multi-omics results return, citing participant rights to their data and perception of minimal harm. Ethical and logistical concerns around the return of multi-omics results were raised, and they often mirrored those in the published literature for genomic return of results including: uncertain clinical validity, a lack of expertise to communicate results, and an unclear obligation regarding whether to return multi-omics results. With the exception of privacy concerns, respondents were able to give examples within multi-omics of how each point was relevant. Further, researchers called for more guidance from funding agencies and increased researcher education regarding return of results. Conclusion Overall, researchers expressed positive attitudes toward multi-omic return of results in principle, particularly if medically actionable. However, competing ethical considerations, logistical constraints, and need for more external guidance were raised as key implementation concerns. Future studies should consider views and experiences of other relevant stakeholders, specifically clinical genomics professionals and study participants, regarding the clinical utility of multi-omics information and multi-omics results return. (shrink)

While it is generally agreed that the concept of homology refers to individuated traits that have been inherited from common ancestry, we still lack an adequate account of trait individuation or inheritance. Here I propose that we utilize a counterfactual criterion of causation to link each trait with a developmental-causal (DC) gene. A DC gene is made up of the genetic information (which might or might not be physically contiguous in the genome) that is needed for the production of (...) the organismic attributes that comprise the trait. I argue that individuated traits—phenes—correspond to organismic features that are caused by DC genes. Using such an approach, we can define a DC map, which shows the relations between each pair of phenes and provides a succinct summary of genotype-phenotype relationships and phenotypic complexity. Phenes in parents and offspring are judged to be homologous if their DC genes are composed of orthologous genetic factors. When comparing more distantly related organisms, traits are homologous when linked by a chain of parent-offspring homologs along the path of ancestry that links the two organisms. There are three possible ways to deal with the potential for multiple equivalent DC genes: maximal, minimal, and consensus homology. Whereas maximal homology has limited utility, the other two approaches have value and can help to guide research at the intersection of evolution and development. (shrink)

Insight into animal biology and development provided by classical genetic analysis of the model organism Drosophila melanogaster was an incentive to develop advanced genetic tools for this insect. But genetic systems for the over one million other known insect species are largely undeveloped. With increasing information about insect genomes resulting from next generation sequencing, RNA interference is now the method of choice for reverse genetics, although it is constrained by the means of delivery of interfering RNA. A recent advance to (...) ensure sustained delivery with minimal experimental intervention or trauma to the insect is to exploit commensal bacteria for symbiont‐mediated RNA interference. This technology not only offers an efficient means for RNA interference in insects in laboratory conditions, but also has potential for use in the control of human disease vectors, agricultural pests and pathogens of beneficial insects. (shrink)

Trichoplax adhaerens is more simply organized than any other living metazoan. This tiny marine animal looks like a irregular “hairy plate” (“tricho plax”) with a simple upper and lower epithelium and some loose cells in between. After its original description by F.E. Schulze 1883, it attracted particular attention as a potential candidate representing the basic and ancestral state of metazoan organization. The lack of any kind of symmetry, organs, nerve cells, muscle cells, basal lamina and extracellular matrix originally left little (...) doubt about the basal position of T. adhaerens. Nevertheless, the interest of zoologists and evolutionary biologists suddenly vanished for more than half a century when Trichoplax was claimed to be an aberrant hydrozoan planula larva. Recently, Trichoplax has been rediscovered as a key species for unraveling early metazoan evolution. For example, research on regulatory genes and whole genome sequencing promise insights into the genetics underlying the origin and development of basal metazoan phyla. Trichoplax offers unique potential for understanding the minimal requirements of metazoan animal organization. BioEssays 27:1294–1302, 2005. © 2005 Wiley Periodicals, Inc. (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)

Malignant tumours are often characterised by significant rearrangement of the genome. This may be visible in the form of a deranged karyotype with both loss and gain of DNA sequences extending from chromosomal regions to whole chromosomes. In several tumour types, however, gross genomic derangements are minimal, and tumour cells contain one or more additional (supernumerary) chromosomes that may be unrecognisable in terms of a single origin. In this review we term such chromosomes cancer‐associated neochromosomes (CaNCs). In the (...) absence of other identified genomic abnormalities, and because the CaNC is a common feature of the cancer type, it is hypothesised that the genetic alterations required for cell transformation are contained within its structure. In this review, we discuss the potential impact of modern genomic technologies on our understanding of the nature and causes of CaNC formation, which is central to several cancer types, exemplified here by well‐differentiated liposarcoma. (shrink)

During the past decades, our image ofHomo neanderthalensishas changed dramatically. Initially, Neanderthals were seen as primitive brutes. Increasingly, however, Neanderthals are regarded as basically human. New discoveries and technologies have led to an avalanche of data, and as a result of that it becomes increasingly difficult to pinpoint what the difference between modern humans and Neanderthals really is. And yet, the persistent quest for a minimal difference which separates them from us is still noticeable in Neanderthal research. Neanderthal discourse (...) is a vantage point from which the logic of ‘us’ versus ‘other’ is critically reconsidered. Studying contemporary academic literature and science autobiographies from an oblique perspective, focusing not on Neanderthals as objects, but on the dynamics of interaction between Neanderthal researchers and their finds, basic convictions at work in this type of research are retrieved. What is at issue is not the actual distinction between modern humans and Neanderthals, but rather the dualistic construction of human and nonhuman. Neanderthal understanding is affected by the desire to safeguard human uniqueness. The overall trend is to identify the human mark or spark, which defines us as favoured ‘winners’. The paradoxes emerging in contemporary Neanderthal discourse are symptomatic of the fact that a dualistic style of thinking is no longer tenable. (shrink)

The theme of the third annual Spring workshop of the HUPO-PSI was proteomics and beyond and its underlying goal was to reach beyond the boundaries of the proteomics community to interact with groups working on the similar issues of developing interchange standards and minimal reporting requirements. Significant developments in many of the HUPO-PSI XML interchange formats, minimal reporting requirements and accompanying controlled vocabularies were reported, with many of these now feeding into the broader efforts of the Functional Genomics (...) Experiment data model and Functional Genomics Ontology ontologies. (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)

As genomic science has evolved, so have policy and practice debates about how to describe and evaluate the ways in which genomic information is treated for individuals, institutions, and society. The term genetic exceptionalism, describing the concept that genetic information is special or unique, and specifically different from other kinds of medical information, has been utilized widely, but often counterproductively in these debates. We offer genomic contextualism as a new term to frame the characteristics of genomic science in the debates. (...) Using stasis theory to draw out the important connection between definitional issues and resulting policies, we argue that the framework of genomic contextualism is better suited to evaluating genomics and its policy-relevant features to arrive at more productive discussion and resolve policy debates. (shrink)

One of central problems in the theory of conditionals is the construction of a probability space, where conditionals can be interpreted as events and assigned probabilities. The problem has been given a technical formulation by van Fraassen (23), who also discussed in great detail the solution in the form of Stalnaker Bernoulli spaces. These spaces are very complex – they have the cardinality of the continuum, even if the language is finite. A natural question is, therefore, whether a technically simpler (...) (in particular finite) partial construction can be given. In the paper we provide a new solution to the problem. We show how to construct a finite probability space $$\mathrm {S}^\#=\left(\mathrm\Omega^\#,\mathrm\Sigma^\#,\mathrm P^\#\right)$$ S # = Ω #, Σ #, P # in which simple conditionals and their Boolean combinations can be interpreted. The structure is minimal in terms of cardinality within a certain, naturally defined class of models – an interesting side-effect is an estimate of the number of non-equivalent propositions in the conditional language. We demand that the structure satisfy certain natural assumptions concerning the logic and semantics of conditionals and also that it satisfy PCCP. The construction can be easily iterated, producing interpretations for conditionals of arbitrary complexity. (shrink)

Recent discussions of genomics and international justice have adopted the concept of ‘global public goods’ to support both the view of genomics as a benefit and the sharing of genomics knowledge across nations. Such discussion relies on a particular interpretation of the global public goods argument, facilitated by the ambiguity of the concept itself. Our aim in this article is to demonstrate this by a close examination of the concept of global public goods with particular reference to its use in (...) the context of genomic databases. We contend that the argument for construing genomics as a global public good depends on seeing it as a natural good by focusing on features intrinsic to genomics knowledge. We shall argue that social and political arrangements are relevant and that recognising this opens the door to construing the use of global public goods language as a strategic one. (shrink)

How should we regulate genome editing in the face of persistent substantive disagreement about the moral status of this technology and its applications? In this paper, we aim to contribute to resolving this question. We first present two diametrically opposed possible approaches to the regulation of genome editing. A first approach, which we refer to as “elitist,” is inspired by Joshua Greene’s work in moral psychology. It aims to derive at an abstract theoretical level what preferences people would (...) have if they were committed to implementing public policies regulating genome editing in a context of ethical pluralism. The second approach, which we refer to as the democratic approach, defended by Francoise Baylis and Sheila Jasanoff et al., emphasizes the importance of including the public’s expressed attitudes in the regulation of genome editing. After pointing out a serious shortcoming with each of these approaches, we propose our own favored approach—the “enlightened democracy” approach—which attempts to combine the strengths of the elitist and democratic approaches while avoiding their weaknesses. (shrink)

In 1990 the Human Genome Project (HGP) was launched as an important historical marker, a pivotal contribution to the time-old quest for human self-knowledge. However, when in 2001 two major publications heralded its completion, it seemed difficult to make out how the desire for self-knowledge had really been furthered by this endeavor (IHGSC 2001; Venter et al. 2001). In various ways mankind seems to stand out from other organisms as a unique type of living entity, developing a critical perspective (...) on its own behavior and consciously engaged in building a complex society of its own making—and therefore increasingly able to determine the conditions of its own evolution. However, this uniqueness is not easily and .. (shrink)

CRISPR is widely considered to be a disruptive technology. However, when it comes to the most controversial topic, germline genome editing (GGE), there is no consensus on whether this technology has any substantial advantages over existing procedures such as embryo selection after in vitro fertilization (IVF) and preimplantation genetic diagnosis (PGD). Answering this question, however, is crucial for evaluating whether the pursuit of further research and development on GGE is justified. This paper explores the question from both a clinical (...) and a moral viewpoint, namely whether GGE has any advantages over existing technologies of selective reproduction and whether GGE could complement or even replace them. In a first step, I review an argument of extended applicability. The paper confirms that there are some scenarios in which only germline intervention allows couples to have (biologically related) healthy offspring, because selection will not avoid disease. In a second step, I examine possible moral arguments in favour of genetic modification, namely that GGE could save some embryos and that GGE would provide certain benefits for a future person that PGD does not. Both arguments for GGE have limitations. With regard to the extended applicability of GGE, however, a weak case in favour of GGE should still be made. (shrink)

It is frequently said that biology is emerging from a long phase of reductionism. It would be certainly more correct to say that biologists are abandoning a certain form of reductionism. We describe this past form, and the experiments which challenged the previous vision. To face the difficulties which were met, biologists use a series of concepts and metaphors - pleiotropy, tinkering, epigenetics - the ambiguity of which masks the difficulties, instead of solving them. In a similar way, the word (...) “post-genomics” has different meanings, depending upon who uses it. Which of these meanings will become dominant in the future is an open question. (shrink)

Genomics holds significant potential for conservationists, offering tools to monitor species risks, enhance conservation strategies, envision biodiverse futures, and advance climate justice. However, integrating genomics into conservation requires careful consideration of its impacts on biodiversity, the diversity of scientific researchers, and governance strategies for data usage. These factors must be balanced with the varied interests of affected communities and environmental concerns. We argue that conservationists should engage with diverse communities, particularly those historically marginalized and most vulnerable to climate change. This (...) inclusive approach can ensure that genomic technologies are applied ethically and effectively, aligning conservation efforts with broader social and environmental justice goals. Engaging diverse stakeholders will help guide responsible genomic integration, fostering equitable and sustainable conservation outcomes. (shrink)

A minimal truthmaker for a given proposition is the smallest portion of reality which makes this proposition true. Minimal truthmakers are frequently mentioned in the literature, but there has been no systematic account of what they are or of their importance. In this article we shall clarify the notion of a minimal truthmaker and argue that there is reason to think that at least some propositions have minimal truthmakers. We shall then argue that the notion can (...) play a useful role in truthmaker theory, by helping to explain the truth of certain propositions as precisely as possible. (shrink)

In this paper I argue that some human reproductive genome editing interventions can be therapeutic in nature, and thus that it is false that all such interventions just create healthy individuals. I do this by showing that the conditions established by a therapy definition are met by certain reproductive genome editing interventions. I then defend this position against two objections: (a) reproductive genome editing interventions do not attain one of the two conditions for something to be a (...) therapy, and (b) some reproductive genome editing interventions are therapeutic but in a nonstandard way. In the Conclusion I call for a more nuanced discussion of the nature of reproductive genome editing interventions. (shrink)

Minimal responsibility threateners are epistemically justified but mistaken in thinking that imposing a nonnegligible risk on others is permissible. On standard accounts, an MRT forfeits her right not to be defensively killed. I propose an alternative account: an MRT is liable only to the degree of harm equivalent to what she risks causing multiplied by her degree of responsibility. Harm imposed on the MRT above that amount is justified as a lesser evil, relative to allowing the MRT to kill (...) her victim. This hybrid account, which generalizes to those are who are more than minimally responsible, has considerable advantages. (shrink)

Genomics is increasingly becoming an integral component of health research and clinical care. The perceived difficulties associated with genetic research involving Aboriginal and Torres Strait Islander people mean that they have largely been excluded as research participants. This limits the applicability of research findings for Aboriginal and Torres Strait Islander patients. Emergent use of genomic technologies and personalised medicine therefore risk contributing to an increase in existing health disparities unless urgent action is taken. To allow the potential benefits of genomics (...) to be more equitably distributed, and minimise potential harms, we recommend five actions: ensure diversity of participants by implementing appropriate protocols at the study design stage; target diseases that disproportionately affect disadvantaged groups; prioritise capacity building to promote Indigenous leadership across research professions; develop resources for consenting patients or participants from different cultural and linguistic backgrounds; and integrate awareness of issues relating to Indigenous people into the governance structures, formal reviews, data collection protocols and analytical pipelines of health services and research projects. (shrink)

The prospect of using genome technologies to modify the human germline has raised profound moral disagreement but also emphasizes the need for wide-ranging discussion and a well-informed policy response. The Hinxton Group brought together scientists, ethicists, policymakers, and journal editors for an international, interdisciplinary meeting on this subject. This consensus statement formulated by the group calls for support of genome editing research and the development of a scientific roadmap for safety and efficacy; recognizes the ethical challenges involved in (...) clinical reproductive applications of genome editing but, importantly, rejects the idea that human reproductive germline modification is necessarily morally unacceptable; and highlights the importance of meaningful engagement in discussions of genome editing and the development of regulation and oversight mechanisms to govern future uses of such technologies. (shrink)

Somatic diversification of antigen receptor genes depends on the activity of enzymes whose homologs participate in a mutagenic DNA repair in unicellular species. Indeed, by engaging error-prone polymerases, gap filling molecules and altered mismatch repair pathways, lymphocytes utilize conserved components of genomic stress response systems, which can already be found in bacteria and archaea. These ancient systems of mutagenesis and repair act to increase phenotypic diversity of microbial cell populations and operate to enhance their ability to produce fit variants during (...) stress. Coopted by lymphocytes, the ancient mutagenic processing systems retained their diversification functions instilling the adaptive immune cells with enhanced evolvability and defensive capacity to resist infection and damage. As reviewed here, the ubiquity and conserved character of specialized variation-generating mechanisms from bacteria to lymphocytes highlight the importance of these mechanisms for evolution of life in general. (shrink)