SummarySynthetic 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.

“Basic research” is often used in science policy. It is commonly thought to refer to research that is directed solely toward acquiring new knowledge rather than any more practical objective. Recently, there has been considerable concern about the future of basic research because of purported changes in the nature of knowledge production and increasing pressures on scientists to demonstrate the social and economic benefits of their work. But is there really something special about basic research? The author argues here that “basic research” is a flexible and ambiguous concept that is drawn on by scientists to acquire prestige and resources. She shows that it is used for boundary work and gives examples of the work it does in different situations by drawing on interviews with scientists and policy makers on the category of basic research and the changes they have seen in it over time.

Human enteroviruses (EV) and parechoviruses (HPeV) within the family Picornaviridae are the most common causes of viral central nervous system (CNS)associated infections including meningitis and neonatal sepsis-like disease. The frequencies of EV and HPeV types identified in clinical specimens collected in Scotland over an eight-year period were compared to those identified in sewage surveillance established in Edinburgh. Of the 35 different EV types belonging to four EV species (A to D) and the four HPeV types detected in this study, HPeV3 was identified as the most prevalent picornavirus in cerebrospinal fluid samples, followed by species B EV. Interestingly, over half of EV and all HPeV CNS-associated infections were observed in young infants (younger than three months). Detection of species A EV including coxsackievirus A6 and EV71 in clinical samples and sewage indicates that these viruses are already widely circulating in Scotland. Furthermore, species C EV were frequently identified EV in sewage screening but they were not present in any of 606 EV-positive clinical samples studied, indicating their likely lower pathogenicity. Picornavirus surveillance is important not only for monitoring the changing epidemiology of these infections but also for the rapid identification of spread of emerging EV and/or HPeV types.

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Human parechoviruses (HPeVs) are highly prevalent RNA viruses classified in the family Picornaviridae. Several antigenically distinct types circulate in human populations worldwide, whilst recombination additionally contributes to the genetic heterogeneity of the virus. To investigate factors influencing the likelihood of recombination and to compare its dynamics among types, 154 variants collected from four widely geographically separated referral centres (UK, The Netherlands, Thailand and Brazil) were typed by VP3/VP1 amplification/sequencing with recombination groups assigned by analysis of 3Dpol sequences. HPeV1B and HPeV3 were the most frequently detected types in each referral region, but with marked geographical differences in the frequencies of different recombinant forms (RFs) of types 1B, 5 and 6. HPeV1B showed more frequent recombination than HPeV3, in terms both of evolutionary divergence and of temporal/geographical indicators of population separation. HPeV1 variants showing between 10 and 20 % divergence in VP3/VP1 almost invariably fell into different recombination groups, compared with only one-third of similarly divergent HPeV3 variants. Substitution rates calculated by BEAST in the VP3/VP1 region of HPeV1 and HPeV3 allowed half-lives of the RFs of 4 and 20 years, respectively, to be calculated, estimates fitting closely with their observed lifespans based on population sampling. The variability in recombination dynamics between HPeV1B and HPeV3 offers an intriguing link with their markedly different seasonal patterns of transmission, age distributions of infection and clinical outcomes. Future investigation of the epidemiological and biological opportunities and constraints on intertypic recombination will provide more information about its influence on the longer term evolution and pathogenicity of parechoviruses.

Research collaborationsUniversity-industry research collaborations in the UK: bibliometric trends J Calvert and P Patel Despite increasing interest amongst policy makers and academics, there have been few attempts at gathering systematic data on the nature and extent of research collaborations between universities and industry. This paper uses joint scientific publications as an indicator of such collaborations in the UK over 20 years. It finds that, although there has been a rapid increase in the volume of university-industry collaborations since the 1980s, the biggest increases were before the major policy measures of the mid-1990s. An important factor would appear to be the growing need for firms, especially non-British firms, to collaborate with leading-edge academic research in promising areas of new technology.Parimal Patel is a senior research fellow at

Patients with chronic mucocutaneous candidiasis (CMC) are selectively unable to clear the yeast Candida, which results in persistent debilitating infections affecting the skin, nails, and mucous membranes. The underlying defect is unknown. Recent animal studies highlighted the importance of type 1 cytokines in protection against Candida, and previous work suggested that CMC patients may exhibit altered cytokine production in response to Candida. Based on these findings, in this study we investigated cytokine production in CMC patients by assessing a range of inflammatory, anti-inflammatory, type 1, and type 2 cytokines ), as well as non-Candida antigens. Our results demonstrate that cytokine production is deregulated in a Candida-specific way for some cytokines (IL-2, IL-10), is deregulated more generally for other cytokines (IL-12, IL-6, IFN-␥), and is not markedly altered for still other cytokines (TNF-␣, IL-4, IL-5).The most notable finding in CMC patients was the markedly impaired production of IL-12 in parallel with dramatically increased levels of IL-6 and IL-10 that occurred selectively in response to Candida. These results suggest that patients with CMC have impaired production of type 1-inducing cytokines (possibly a macrophage or dendritic cell defect?), which could result in an inability to mount protective cell-mediated responses and a failure to clear Candida. Continued tissue damage and inflammation may trigger production of high levels of inhibitory cytokines, such as the IL-10 production seen in our study, which would further reduce production of type 1-inducing cytokines in a positive feedback loop leading to persistent infection.

Based on criticism of the “ethical, legal and social implications” (ELSI) paradigm, researchers in science and technology studies (STS) have begun to create and move into “post-ELSI” spaces. In this paper, we pool our experiences of working towards collaborative practices with colleagues in engineering and science disciplines in the field of synthetic biology. We identify a number of different roles that we have taken, been assumed to take, or have had foisted upon us as we have sought to develop post-ELSI practices. We argue that the post-ELSI situation is characterised by the demands placed on STS researchers and other social scientists to fluctuate between roles as contexts shift in terms of power relations, affective tenor, and across space and over time. This leads us to posit four orientations for post-ELSI collaborative practices that could help establish more fruitful negotiations around these roles.