SYNMOD_Biosafety and biosecurity, public perception

Synmod proposes to apply a comprehensive synthetic biology approach to the design and production of novel antibiotic molecules. First, evolutionarily pre-determined peptide modules are precisely defined and then re- combined for novel antibiotic functions. The modules are obtained from the group of lantibiotics, post- translationally modified peptide antibiotics. Next, we will assemble a contextinsensitive post-translational machinery by exploiting promiscuous modification enzymes and enabling a fine-tuning of the composition of the modification pathway. This will be obtained by organizing the pathway in a modular fashion and providing thoroughly characterized expression elements. This pathway will then be implemented in a novel production chassis of reduced complexity, specifically the Gram-positive Staphylococcus carnosus (2.56 Mg genome), and the resulting strain will be used to manufacture preparative quantities of a variety of novel lantibiotics. By consequently the principles of modularity and context-insensitivity on the various levels of the engineering process, we attempt to provide a antibiotic design and production system of unusual robustness and predictability. Using this project as a concrete example, we will analyze the potential impact of synthetic biology on the safety of biotechnological processes and its ethical implications for our society. These considerations will be shared with the public to institute a constructive dialogue about a potentially transformative novel technology.

Up to the point when Antibiotics were discovered, infectious diseases were a permanent threat to health and even life. Hardly any other scientific or medical discovery had such a positive impact on the wellbeing and safety of the entire population. Antibiotics where prescribed heavily to fight disease, but some patients didnt take their medicine as indicated but stopped midway their treatment. In some of those cases the pathogen developed a tolerance or even resistance to the antibiotic, which meant these antibiotics were no longer effective. For most of the time other antibiotics that were discovered in nature where then used to combat multi-drug resistant bacteria. Recently the number of new antibiotics has stalled, for technical reasons (no more new antibiotics are found in nature) and socio-economic reasons (the pharmaceutical industry has lost its interest since little return on investment is foreseen). In the international research project SYNMOD a new approach to come up with novel antibiotics was introduced. The aim of SYNMOD was to take a certain class of antibiotics, so-called lantibiotics, and cut them into a number of modules. These modules were then reassembled into thousands of new combinations and then tested against pathogens in specially crafted testing devices. The Austrian part of the project dealt with the societal implications of the design and production of synthetic lantibiotics. In particular we explored the interface between science and society, and asked questions like: What are the ethical issues involved in SYNMOD? Which new biosafety challenges have to be considered? How does the philosophical understanding of life impinge on the debate about synthetic biology? How could the project be presented and communicated to the broader public? Our results show that synthetic biology in relation to the production of medical or pharmaceutical products is generally not seen as ethically problematic. The only critique is the extensive use of antibiotics in livestock production in industrial agriculture that has been shown to influence antibiotic resistance in humans. A modularisation in biotechnology means also a production simplification that automatically leads to an extension of the user base of the technology. In other words, more people outside traditional biotechnology institutions (universities, high tech companies) will use synthetic biology. Among this enlarged user base are so-called biohackers or do-it-yourself biologists that can be seen as part of a broader citizen science movement. While the media and some scientists have depicted biohackers as a safety and security risk, our analysis has shown that biohackers are semi-professional enthusiasts who aim to democratize production processes in biotechnology. Contrary to big pharmaceutical companies, these biohackers keep working on innovative solutions even if there is hardly any return of investment to be expected. Whether or not biohackers will be able to come up with meaningful solutions for the antibiotics crisis remains to be seen, but at least they address the socio-economic reason why no more new antibiotics are developed by industry.