Johannes Rath

The α-d-mannan core of a complex cell-wall heteroglycan of Trichoderma reesei is responsible for β-glucosidase activation

Abstract A heteroglycan responsible for the binding of the enzyme β-1,4-d-glucosidase (EC 3.2.1.21) to fungal cell walls was isolated from cell walls of the filamentous fungus Trichoderma reesei. The heteroglycan, composed of mannose, galactose, glucose, and glucuronic acid, also activated β-1,4-d-glucosidase, β-1,4-d-xylosidase and N-acetyl-β-1,4-d-glucosaminidase activity in vitro. The structural backbone of this heteroglycan was prepared by acid hydrolysis and gel filtration. The molecular structure of the core of the heteroglycan was determined by NMR studies as a linear α-1,6-d-mannan. The mannan core obtained by acid degradation stimulated the β-glucosidase activity by 90%. Several glycosidases from Aspergillus niger were also activated by the T. reesei heteroglycan. The β-glucosidase of Trichoderma was activated by mannan from Saccharomyces cerevisiae to a comparable extent.

Biological Weapons Control

The current negotiations in Geneva to develop a legally binding instrument to strengthen the 1972 Biological and Toxin Weapons Convention (BTWC) are likely to result in an international declaration and inspection regime. This regime could have implications for both academic and industrial research, development, and production sites. In a recent Policy Forum ( Science s Compass, 20 Nov., p. [1423][1]), Thomas P. Monath and Lance K. Gordon express their concerns about on-site inspections in biological weapons control, concluding with support of the concept and leaning toward on-site inspections with sampling at the site triggered by national “intelligence-gathering activities.” At an international symposium held at the Institute for Applied Microbiology, Vienna, Austria, in May 1998, the value of on-site inspections and sampling in a possible future biological weapons control regime was also addressed. The participants came from varied backgrounds: regulatory affairs and biosafety managers from industry and academia, diplomats, weapons inspectors, and representatives of various international and national authorities. They concluded that triggering inspections through suspicion could very likely stigmatize any of the inspected institutions. In principal, a biological weapons control regime includes auditing, which presents the possibility of certifying that the site is compliant with the agreements on production, stockpiling, and use of biological weapons. If sites that possess dual use capabilities are inspected at random intervals, the inspection itself would leave no stigma; on the contrary, the outcome of the inspection could increase the level of confidence that the institution is complying with international agreements. This could reduce the need for restrictions in the international exchange of dual-use material, equipment, and know-how, a fear expressed at the symposium. The delegates suggested that, to minimize the extra workload, a future protocol should take into account existing control regimes. For biopharmaceutical industries, in particular, consideration should be given to how the new protocol could be implemented nationally through use of existing infrastructures, such as those established under health and safety legislation. # Response {#article-title-2} As Rath, Jank, and Doblhoff-Dier correctly point out, there is considerable debate about the pros and cons of an inspection regime as a means of enforcing the ban on biological weapons. We would like to correct one apparent misinterpretation of our position, with respect to triggers for visits. We do not suggest that the selection of facilities for inspection would be based principally on “intelligence-gathering activities.” Rather, it is anticipated that the content of declarations submitted by states or parties containing information about activities at research and production sites, specific biological agents, biological weapons defensive research, aerosol studies, containment level, and so forth will be the basis for visits. A system for right of entry to declared sites is needed to increase transparency and reduce suspicions. The declaration process has revealed, and will continue to reveal questions that can be clarified most effectively by on-site visits. Serious concerns about potential violations can be resolved only by challenge inspections, which would be conducted at very short notice and would be based on information sufficient to pass stringent criteria. Without challenge inspections and the possibility of on-site analysis, the treaty would remain a “dog without teeth.” It is likely that those states engaged in offensive biological research and development will continue to deceive the international community and that illegal activities will be carried out at undeclared facilities. Ultimately, intelligence gathering may be useful in revealing such facilities and bringing them under the scrutiny of the inspectorate. It is our expectation, however, that some states or parties may decide that it is not worth the political and economic risk to initiate (or continue) offensive programs. The threat of enforcement of the Chemical Weapons Treaty resulted in the declaration and abandonment of previously denied programs. We do not share the same apprehension expressed by participants at the Vienna conference with respect to the stigma attached to visits and inspections. Intrusive visits by various regulators are already frequent occurrences, and once biological weapons visits become regular events, they will hardly be “news.” We also do not share the view that the fox should guard the henhouse; self-enforcement through national legislation does not provide a reasonable safeguard against state-sponsored biological weapons programs [1]: /lookup/doi/10.1126/science.282.5393.1423

Evolution of Different Dual-use Concepts in International and National Law and Its Implications on Research Ethics and Governance

This paper provides an overview of the various dual-use concepts applied in national and international non-proliferation and anti-terrorism legislation, such as the Biological and Toxin Weapons Convention, the Chemical Weapons Convention and United Nations Security Council Resolution 1540, and national export control legislation and in relevant codes of conduct. While there is a vast literature covering dual-use concepts in particular with regard to life sciences, this is the first paper that incorporates into such discussion the United Nations Security Council Resolution 1540. In addition, recent developments such as the extension of dual-use export control legislation in the area of human rights protection are also identified and reviewed. The discussion of dual-use concepts is hereby undertaken in the context of human- and/or national-security-based approaches to security. This paper discusses four main concepts of dual use as applied today in international and national law: civilian versus military, peaceful versus non-peaceful, legitimate versus illegitimate and benevolent versus malevolent. In addition, the usage of the term to describe positive technology spin-offs between civilian and military applications is also briefly addressed. Attention is also given to the roles civil society and research ethics may play in the governance of dual-use sciences and technologies.

Lessons learned from implementing education on dual-use in Austria, Italy, Pakistan and Sweden

This paper provides insights into the achievements and challenges of implementing education on dual-use in four countries: Austria, Italy, Pakistan and Sweden. It draws attention to the different institutional mechanisms through which dual-use education may be introduced into academic curricula and some of the difficulties encountered in this process. It concludes that there is no ‘one size fits all’ approach to the implementation of dual-use education. Rather, initiatives must be tailored to suit the teaching traditions, geographical and historical context in which they are being delivered. However, a number of common principles and themes can be derived from all four cases. All these courses bring together a number of different topics that place ‘dual-use’ in the broader context of biosafety, biosecurity, ethics, law and the environment. The case studies suggest that success in this area depends largely on the leadership and commitment of individuals directly involved in teaching, who are active within the scientific community.

The Risk of Pyrrolizidine Alkaloids in Human Food and Animal Feed

Toxicity from naturally occurring plant pyrrolizidine alkaloids bears substantial risk to humans and livestock. Risk management strategies must focus on minimizing the likelihood of such alkaloids entering into the food chain. To address this challenge, we describe the role of a tiered risk characterization approach and specific farm management practices.

Fostering responsible research with genome editing technologies: a European perspective

In this consensus paper resulting from a meeting that involved representatives from more than 20 European partners, we recommend the foundation of an expert group (European Steering Committee) to assess the potential benefits and draw-backs of genome editing (off-targets, mosaicisms, etc.), and to design risk matrices and scenarios for a responsible use of this promising technology. In addition, this European steering committee will contribute in promoting an open debate on societal aspects prior to a translation into national and international legislation.

Safety and Security Risks of CRISPR/Cas9

This case study looks into recent developments with regard to the CRISPR/Cas9 and other novel genome editing technologies that are becoming widely available thanks to their low costs and modest technological requirements.

Codex guideline and Food and Agriculture Organization database on low-level presence of genetically modified plants.

An increasing number of genetically modified (GM) plants are being approved for commercialization. However, different countries authorize use of certain GM plants at different times. As a consequence of these so-called ‘asymmetric authorizations’, low levels of GM plant material that have passed a food safety assessment in one country may on occasion be present in food in an importing country that has not yet determined the food safety of that GM plant.

Rules of engagement: Restricting security‐sensitive research data—a European view

The recent discussion about how to handle the results of security‐relevant “dual‐use” research has generated substantial polarization among stakeholders. In essence, there are two major options to prevent the abuse or misuse of research data: to restrict research itself so as to prohibit certain experiments, or to restrict the publication of research that could be abused by the military, terrorists or criminals. The case in question was the gain‐of‐function experiments by a research group in the Netherlands that created a strain of the H5N1 virus with increased transmissibility among mammals. The initial recommendation by the US National Science Advisory Board for Biosecurity (NSABB) was to allow only limited access to crucial data in the publications, which raised the ire of the scientific community who were concerned that their freedom of research could be curtailed in the name of security. When a Dutch district court eventually ruled in favour of the publication of H5N1 gain‐of‐function research—but upheld the requirement to apply for export licences [1]—it was obvious that the final judgment over restricting the publication of security‐sensitive research data will rest on the judicial system and neither on individual or collective self‐governance by the research community, nor advisory boards such as the NSABB. Indeed, a key problem in finding common ground between those who are concerned about security and those who defend the freedom of research is the unresolved issue over who will have to make such decisions and which procedural principles to manage the risks of publication should be applied. This paper addresses this issue by looking into the pros and cons of different risk management concepts that have been suggested to resolve the dilemma, such as risk–benefit assessment, the Precautionary Principle or the Proportionality Principle. Notwithstanding who will eventually have to make decisions about information security—scientists, regulators …