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‘Test and Trace’ systems are key components of national responses to the ongoing COVID-19 pandemic. Each country has its own set of measures for testing COVID-19 cases, finding contacts, and isolating and supporting those affected by the SARS-CoV-2 virus. This article presents early results from a comparative analysis of six countries; Germany, Ireland, Spain, South Africa, South Korea, and the UK. Using evidence from publicly available sources, the paper presents analyses of testing systems in the study countries, using a Find, Test, Trace, Isolate, and Support (FTTIS) framework. The article demonstrates that no single study country has a fully optimised FTTIS system, with lessons to be learned for all from international comparisons. Findings emphasise lessons for the countries studied as well as general lessons of wider relevance on the potential scope of FTTIS systems. In particular, the need for openness and evaluation is emphasised as an integral part of the FTTIS system, to support continual assessment, learning, evolution and international sharing of good practice.

We analysed the decisions of major European public funding organisations to fund or not to fund synthetic biology (SB) and related ethical, legal and social implication (ELSI) studies. We investigated the reaction of public organisations in six countries (Austria, France, Germany, the Netherlands, Switzerland and the UK) towards SB that may influence SB’s further development in Europe. We examined R&D and ELSI communities and their particular funding situation. Our results show that the funding situation for SB varies considerably among the analysed countries, with the UK as the only country with an established funding scheme for R&D and ELSI that successfully integrates these research communities. Elsewhere, we determined a general lack of funding (France), difficulties in funding ELSI work (Switzerland), lack of an R&D community (Austria), too small ELSI communities (France, Switzerland, Netherlands), or difficulties in linking existing communities with available funding sources (Germany), partly due to an unclear SB definition.

Three different resistance factors from the avilamycin biosynthetic gene cluster of Streptomyces viridochromogenes Tü57, which confer avilamycin resistance when expressed in Streptomyces lividans TK66, were isolated. Analysis of the deduced amino acid sequences showed that AviABC1 is similar to a large family of ATP-binding transporter proteins and that AviABC2 resembles hydrophobic transmembrane proteins known to act jointly with the ATP-binding proteins. The deduced amino acid sequence of aviRb showed similarity to those of other rRNA methyltransferases, and AviRa did not resemble any protein in the databases. Independent expression in S. lividans TK66 of aviABC1 plus aviABC2, aviRa , or aviRb conferred different levels of resistance to avilamycin: 5, 10, or 250 μg/ml, respectively. When either aviRa plus aviRb or aviRa plus aviRb plus aviABC1 plus aviABC2 was coexpressed in S. lividans TK66, avilamycin resistance levels reached more than 250 μg/ml. Avilamycin A inhibited poly(U)-directed polyphenylalanine synthesis in an in vitro system using ribosomes of S. lividans TK66(pUWL201) (GWO), S. lividans TK66(pUWL201-Ra) (GWRa), or S. lividans TK66(pUWL201-Rb) (GWRb), whereas ribosomes of S. lividans TK66 containing pUWL201-Ra+Rb (GWRaRb) were highly resistant. aviRa and aviRb were expressed in Escherichia coli , and both enzymes were purified as fusion proteins to near homogeneity. Both enzymes showed rRNA methyltransferase activity using a mixture of 16S and 23S rRNAs from E. coli as the substrate. Coincubation experiments revealed that the enzymes methylate different positions of rRNA.

Die Synthetische Biologie umfasst ein Bundel von Methoden, Techniken und Konzepten zur zielgerichteten Veranderung und Generierung von Organismen. Sie ist ein interdisziplinarer Forschungsansatz, an dem sich neben den Lebenswissenschaften insbesondere die Ingenieurwissenschaften, die Chemie und die Informationstechnologien beteiligen. Die Grundlage der Synthetischen Biologie ist das Verstandnis der einzelnen funktionellen Bausteine einer Zelle auf Ebene der Gene, ihrer Steuerelemente und Regelkreise. Ein intensiver Austausch der beteiligten Disziplinen untereinander, die Entwicklung einer gemeinsamen Sprache und die Verstandigung auf gemeinsame Ziele sind wichtige Voraussetzungen fur die Weiterentwicklung innerhalb der Synthetischen Biologie. Abbildung 1 verdeutlicht das Zusammenspiel der verschiedenen Disziplinen und die daraus resultierenden Produkte und Anwendungen.

Oligonucleotide primers were designed and successfully applied to amplify DNA fragments of dNDP-glucose dehydratase genes from actinomycete species producing natural compounds which contain deoxysugar moieties. The deduced amino acid sequence of the isolated fragments revealed similarity to known dNDP-glucose dehydratases. A phylogeny for the deduced proteins of the obtained fragments and for dNDP-glucose dehydratases described in the data bases was constructed. dNDP-glucose dehydratases from actinomycetes were more related to each other than to dehydratases from species of other orders. The phylogenetic analysis also revealed a close relation between dehydratases from strains producing natural compounds with similar deoxysugar moieties.

Ferric siderophores, vitamin B12, and group B colicins are taken up through the outer membranes of Escherichia coli cells by an energy-coupled process. Energy from the cytoplasmic membrane is transferred to the outer membrane with the aid of the Ton system, consisting of the proteins TonB, ExbB, and ExbD. In this paper we describe two point mutations which inactivate ExbD. One mutation close to the N-terminal end of ExbD is located in the cytoplasmic membrane, and the other mutation close to the C-terminal end is located in the periplasm. E. coli CHO3, carrying a chromosomal exbD mutation in which leucine at position 132 was replaced by glutamine, was devoid of all Ton-related activities. A plasmid-encoded ExbD derivative, in which aspartate at position 25, the only changed amino acid in the predicted membrane-spanning region of ExbD, was replaced by asparagine, failed to restore the Ton activities of strain CHO3 and negatively complemented ExbD+ strains, indicating an interaction of this mutated ExbD with wild-type ExbD or with another component. This component was shown to be ExbB. ExbB that was labeled with 6 histidine residues at its C-terminal end and that bound to a nickel-nitrilotriacetic acid agarose column retained ExbD and TonB specifically; both were eluted with the ExbB labeled with 6 histidine residues, demonstrating interaction of ExbB with ExbD and TonB. These data further support the concept that TonB, ExbB, and ExbD form a complex in which the energized conformation of TonB opens the channels in the outer membrane receptor proteins.

Biotechnological methods have become an important tool in pharmaceutical drug research and development. Today approximately 15 % of drug revenues are derived from biopharmaceuticals. The most relevant indications are oncology, metabolic disorders and disorders of the musculoskeletal system. For the future it can be expected that the relevance of biopharmaceuticals will further increase. Currently, the share of substances in preclinical testing that rely on biotechnology is more than 25 % of all substances in preclinical testing. Products for the treatment of cancer, metabolic disorders and infectious diseases are most important. New therapeutic approaches such as RNA interference only play a minor role in current commercial drug research and development with 1.5 % of all biological preclinical substances. Investments in sustainable high technology such as biotechnology are of vital importance for a highly developed country like Germany because of its lack of raw materials. Biotechnology helps the pharmaceutical industry to develop new products, new processes, methods and services and to improve existing ones. Thus, international competitiveness can be strengthened, new jobs can be created and existing jobs preserved.

Zusammenfassung Die Methoden der Biotechnologie wurden in den letzten 10 Jahren zu einem wichtigen Instrumentarium in der pharmazeutischen Wirkstoffforschung und -entwicklung. Bereits heute machen Biopharmazeutika rund 15% des gesamten Umsatzes mit Arzneistoffen aus. Dabei sind die drei wichtigsten Indikationsgruppen die Onkologie, Stoffwechselerkrankungen und Erkrankungen des Bewegungsapparats. Fur die nachsten Jahre kann damit gerechnet werden, dass Biopharmazeutika weiter an Bedeutung gewinnen. Der Anteil von Substanzen in der praklinischen Forschung, die auf biotechnologischen Verfahren beruhen, liegt mittlerweile bei uber 25%. Neben Produkten fur die Onkologie und Stoffwechselerkrankungen spielen hier Antiinfektiva eine wichtige Rolle. Neuartige Therapieverfahren wie die RNA-Interferenz stecken dagegen mit 1,5% aller kommerziellen Forschungsprojekte noch in den Kinderschuhen. Investitionen in zukunftsfahige Spitzentechnologien wie die Biotechnologie sind fur ein hoch entwickeltes und rohstoffarmes Land wie Deutschland von zentraler Bedeutung. Die Biotechnologie hilft den deutschen Pharmaakteuren vor allem dabei, neue Produkte, Prozesse/ Verfahren und Dienstleistungen zu entwickeln und existierende zu verbessern. Dadurch kann die internationale Wettbewerbsfahigkeit gestarkt, neue Arbeitsplatze in Deutschland konnen geschaffen und bestehende gesichert werden.

Synthetic biology is an emerging field with large potential for research and development, and future benefits for economy and society. The European Union (EU) has started measures to structure and develop the field, such as a high‐level expert group. However, research activities are still scattered across Europe and scientific disciplines, and are concentrated in a relatively small number of working groups. Further integration is also hampered because there is no common understanding of synthetic biology, no clear description of its status quo and no comprehensive assessment of its potential. The situation is similar in the USA, although the field seems to be more advanced there in terms of activity and networking within the scientific community. Accordingly, to strengthen European competitiveness in synthetic biology, it is necessary to integrate the various activities and to draft a comprehensive strategy for the field. > Further integration is hampered because there is no common understanding of synthetic biology, no clear description of its status quo and no comprehensive assessment of its potential We therefore developed a ‘roadmap’ for synthetic biology in Europe, defining the essential steps to be taken in regard to regulation, funding, public‐sector integration and scientific research. Our study, which was supported as part of the New and Emerging Science and Technology (NEST) programme (European Commission, Brussels, Belgium), involved an expert committee and the broader scientific community in an attempt to develop a common understanding of synthetic biology. This process was intended to generate awareness of the field among researchers, funding agencies and research organizations such as the National Academies of Science (Washington, DC, USA), the Max‐Planck‐Society (Munich, Germany) and the Centre National de la Recherche Scientifique (CNRS; Paris, France). > Without public support and understanding of research into synthetic biology, both funding and regulation are unlikely to support significant scientific advances The mapping …

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

This paper reviews the current situation in the field of pharmacogenetics/pharmacogenomics (PGx) in Europe. High expectations surrounding the clinical application of PGx remain largely unmet, as only a limited number of such applications have actually reached the market and clinical practice. Thus, the potential impact of PGx-based diagnostics on healthcare and its socio-economic implications are still unclear. With the aim of shedding some light on these uncertainties, the Institute for Prospective Technological Studies (IPTS) of the European Commission’s Joint Research Centre (JRC) has conducted a review of the ‘state of the art’ and a further analysis on the use of pharmacogenetics diagnostics for preventing toxic drug reactions and improving drug efficacy in Europe. The paper presents highlights from the JRC-IPTS studies and discusses possibilities for improving translation of PGx research in Europe by comparing some experiences in the USA. We also illustrate the related barriers for the clinical uptake of PGx in Europe with specific case-studies. Most of the barriers identified extend beyond the European context. This reflects the global problems of scarcity of data demonstrating proven clinical validity or utility and favorable cost-effectiveness studies to support the clinical application of PGx diagnostic tests in the clinical setting. Another key barrier is the lack of incentives for the private sector to invest in the development and licensing of PGx diagnostic tests for improving the safety and efficacy of out-of-patent drugs. It therefore seems that one key aspect where policy can affect the clinical uptake of PGx is via sustaining large-scale industry-academia collaborations for developing and proving the utility of PGx diagnostics.

Against the background of a number of first drug-diagnostic co-products developed and introduce into the European market, European decision-makers feel impelled to react and position themselves in the field of personalized medicine. Their reactions cover a broad range, from the analysis of knowledge requirements for market approval to the need for translational activities and the possible contribution of pharmacogenetics to public health. This article summarizes the current positions of European institutions, based on literature review and expert consultation for three items associated with personalized medicine: biobanks, genetic diagnostics and drug-diagnostic co-products, and provides an outlook on requirements for an effective futute European policy on personalized medicine. © 2009 Future Medicine Ltd.

This article gives an insight into the uptake of cutting edge technologies such as stem cell technologies, RNAi, and gene therapy by the European pharmaceutical industry. The European situation is benchmarked against the most important competitors - USA and Japan - both in terms of products in the pipeline and on the market. Economic and employment effects illustrate the impact of modern biotechnology for the European economy. Current and future trends and the competitiveness of the European drug developmental pipeline are outlined in terms of relevant indications (e.g., oncology and infectious diseases), the degree of adoption by European companies and the European biotechnological contribution. It shows how national strength in early developmental stages of drug development influences the power of a national market. In this context the role of SMEs and biotechnology start-ups is discussed. The analysis culminates in questioning which factors influence the uptake of technology and the direction of a technology trajectory and which measures are suitable to foster pharmaceutical innovation in general and in CEE in particular.

The cloned sfu region of the Serratia marcescens chromosome confers the ability to grow on iron-limited media to an Escherichia coli K-12 strain that is unable to synthesize a siderophore. This DNA fragment was sequenced and found to contain three genes termed sfuA, sfuB, and sfuC, arranged and transcribed in that order. The sfuA gene encoded a periplasmic polypeptide with calculated molecular weights of 36,154 for the precursor and 33,490 for the mature protein. The sfuB gene product was a very hydrophobic protein with a molecular weight of 56,589. The sfuC gene was found to encode a rather polar but membrane-bound protein with a molecular weight of 36,671 which exhibited strong homology to consensus sequences of nucleotide-binding proteins. The number, structural characteristics, and locations of the SfuABC proteins were typical of a periplasmic-binding-protein-dependent transport mechanism. How Fe3+ is solubilized and taken up across the outer membrane remains an enigma.

Gentechnik ist die Summe aller Methoden zur Isolierung, Charakterisierung, gezielten Veranderung und Ubertragung von Erbgut. Fur die Tierzucht und landwirtschaftliche Nutztierhaltung gliedert sich die Gentechnik in die folgenden drei Bereiche: • „Genomics“ — genanalytische und gendiagnostische Untersuchungen der tierlichen Erbsubstanz ohne gentechnische Veranderung des Erbguts • „Transgenics“ — gentechnische Veranderung des tierlichen Erbgutes; Herstellung transgener Tiere • Einsatz der Gentechnik in der Tierernahrung und -gesundheit.

Die Diskussion um die Risiken und die Sicherheit der Anwendung gentechnischer Methoden und Verfahren im Landwirtschafts-und Lebensmittelbereich ist in Deutschland und in der EU auch mehr als zehn Jahre nach Verabschiedung des Deutschen Gentechnikgesetzes und der Europaischen Freisetzungsrichtlinie (s. Kap. 10) nicht verstummt, sondern hat eher an Intensitat gewonnen. Insbesondere in der zweiten Halfte der 90er Jahre setzte in Landern, in denen zuvor eine eher positive bis neutrale Haltung gegenuber der „Grunen Gentechnik“ zu beobachten war (z. B. Grosbritannien, Frankreich, Mittelmeerstaaten) eine intensive Diskussion insbesondere uber die Sicherheit gentechnisch veranderter Pflanzen und Lebensmittel ein, die auch in diesen Landern in eine eher ablehnende Haltung mundete, die bis dahin vor allem in den mitteleuropaischen Staaten vorherrschte (Menrad 2000, Gaskell et al. 2000). Im folgenden Kapitel wird ein Uberblick uber den Stand der Diskussion zur Sicherheitsforschung und Risikobewertung gentechnischer Methoden und Verfahren im Agro Food-Bereich gegeben. Falls moglich wird dabei spezifisch auf die Verhaltnisse in der EU und Deutschland eingegangen. Zunachst werden die potenziellen Risiken transgener Tiere, transgener Pflanzen sowie beim Verzehr gentechnisch veranderter Lebensmittel dargestellt. Anschliesend wird auf die Kontaminationswege und -folgen einer „unabsichtlichen” Beimischung von gentechnisch verandertem Material sowie der Ruckverfolgbarkeit von GVO eingegangen. Den Abschluss des Kapitels bilden Informationen zu den Nachweismethoden fur gentechnisch veranderte Organismen.

Die Studie wird in die funf Anwendungsfelder der Gentechnik Tierzucht und landwirtschaftliche Nutztierhaltung, Pflanzenzucht, Forstwirtschaft, Landwirtschaft (insbesondere Pflanzenbau) sowie Lebensmittelproduktion untergliedert. Daneben werden zwei anwendungsfeldubergreifende Kapitel erstellt, in denen Aspekte der Sicherheits-und Risikobewertung sowie die rechtlichen Regelungen fur Deutschland und die EU behandelt werden (Abb. 3.1).

Das Ziel der Studie ist es, einen moglichst umfassenden Uberblick uber den Einsatz der Gentechnik in den Anwendungsfeldern Pflanzen-und Tierzucht, Land-und Forstwirtschaft sowie Lebensmittelherstellung zu geben. Fur jedes dieser Anwendungsfelder ist aufzuzeigen, wie der aktuelle internationale Stand von Forschung und Technik unter besonderer Berucksichtigung der okologischen und okonomischen Aspekte ist wie der aktuelle Stand der Diskussion zu Chancen und Risiken ist, welche wirtschaftlichen Perspektiven sich ergeben, welche Forschungsschwerpunkte als besonders zukunftstrachtig einzuschatzen sind, welche rechtlichen Regelungen auf nationaler und EU-Ebene in diesen Feldern bestehen.

Gentechnisch veranderte Pflanzen wurden erstmals im Jahr 1996 kommerziell angebaut. Seitdem ist ein erheblicher jahrlicher Zuwachs der weltweiten Anbauflachen zu beobachten ((Abb. 7.1).). Im Jahr 2001 wurden auf mehr als 52 Mio. ha gentechnisch veranderte Pflanzen angebaut (zum Vergleich die gesamte Flache Deutschlands betragt 35 Mio. ha). Damit hat sich die Anbauflache transgener Nutzpflanzen in den letzten funf Jahren mehr als vervierfacht. Gegenuber dem Vorjahr betragt die Steigerung noch 19% (James 2001).

In this, the second of two Commentaries, Sibylle Gaisser, Michael M. Hopkins and colleagues discuss a survey demonstrating that European health-care systems are ill prepared for the commercial reality of gene patents.

A 65-kb region of DNA from Streptomyces viridochromogenes Tü57, containing genes encoding proteins involved in the biosynthesis of avilamycins, was isolated. The DNA sequence of a 6.4-kb fragment from this region revealed four open reading frames (ORF1 to ORF4), three of which are fully contained within the sequenced fragment. The deduced amino acid sequence of AviM, encoded by ORF2, shows 37% identity to a 6-methylsalicylic acid synthase from Penicillium patulum. Cultures of S. lividans TK24 and S. coelicolor CH999 containing plasmids with ORF2 on a 5.5-kb PstI fragment were able to produce orsellinic acid, an unreduced version of 6-methylsalicylic acid. The amino acid sequence encoded by ORF3 (AviD) is 62% identical to that of StrD, a dTDP-glucose synthase from S. griseus. The deduced amino acid sequence of AviE, encoded by ORF4, shows 55% identity to a dTDP-glucose dehydratase (StrE) from S. griseus. Gene insertional inactivation experiments of aviE abolished avilamycin production, indicating the involvement of aviE in the biosynthesis of avilamycins.

As science unravels the genetic basis of disease, the opportunities offered by pharmacogenetics and pharmacogenomics (PGx) for future healthcare become more and more apparent. The objective of this paper is to analyse the current state of PGx research and explore future strategies for more efficient research projects and supportive infrastructures. Based on internet searches and an online survey of public research groups, the current focus of PGx technology and the institutional framework conditions for its performance were determined. The main areas of PGx research are the liver, neoplasms and the cardiovascular and central nervous systems. Collaborations are important for knowledge transfer between the private and public sectors. However, for strategic and confidentiality reasons, most collaborations are restricted to preclinical development, early stage clinical studies and the development of methods.