As biological engineers we have a great responsibility to the public - our research needs to be done safely. In order to prevent humans and the environment from potentially harmful events, we used taylored methods (e.g. markerless genetic engineering) and followed strict safety regulation rules. We also helped the Dutch Government with brainstorming about the legislation on biosafety of new method and trends in the synthetic biology.
One of the main-reasons for our team to join iGEM, was our general interest in the ethical concerns that come with synthetic biology. We have been well trained and supervised on laboratory safety, thought thoroughly about making our project safe by design, and stayed in contact with the RIVM, the Dutch National Institute for Public health and the Environment and the Rathenau institute throughout our project.
Beyond the scope of our own scientific project, we took the opportunity to get involved in the shaping of the rules of synthetic biology in the Netherlands. To further explore our thoughts and generate a debate on biosafety in synthetic biology, we have also dedicated a part of our podcast series to this topic in which we explore the actual issues in biosafety along with people from RIVM, Synenergene and leading scientists.
We have worked in the academic lab of the Molecular Microbial Physiology (MMP) research group of the University of Amsterdam, which is certified to work with GMO’s. Before starting the iGEM project, we have received thorough safety training from departmental specialists and PIs. We learned the lab rules and received the general wet lab safety training, which covers issues such as waste disposal, working with the general lab equipment and clothing.Throughout the project, experiment specific safety training was also provided on working with less common lab-equipment, for example working with Multi-Cultivators. Additionally, all team-members working in the wet lab have also been under the continuous supervision of Phd-students and technicians throughout the whole iGEM-project. While having access and certification for biosafety level BSL2, we only used a safety level BSL1 lab. This was allowed, since we used risk group 1 chassis organisms For our project we used Synechocystis PPC 6803 and E. coli strains: DH5α, XL1-blue and E10.
Safety by design
From out the start of our project, our top priority was to design our project such that it would be as safe as possible if it would be applied in a biobased economy. This means that the genetic engineering involved in our project poses minimal risks to society. By working together with experts in academia, industry and regulations, we came up with different strategies to reduce these risks. Firstly, We have used the markerless knockout method. Thus our production Synechocystis strains, would not contain any antibiotic resistance cassette, and thereby minimizing the risk in antibiotic resistance spread. Secondly, due to the alterations we make to our cells, the engineered bacterial strains will be hampered in growth rate to such an extent that they will always be out-competed by natural isolates. This gives our final strains bad odds surviving outside the contained environment of the lab or industrial bioreactor.
In a scaled up application of our strains, our cells would be growing in a system which is exposed to light and to which water and CO2 is continuously added, while fumarate will be continuously harvested fig 9.1. Assessing a worst case scenario event of bio hazard in which for example a bioreactor with our strain would leak into a lake. Our cells would be out-competed by Wild Type cyanobacteria, and be unable to colonize such environments. Meanwhile, they would not be able to pass on genes that would lead to fitness increase to other bacteria, minimizing the risk of undesirable effects.
The Future of Biosafety in synthetic biology
At the start of our project, we have visited a session at the Rathenau institute, where people from the RIVM assessed our research-plans. As we are very interested by the topic of biosafety we have stayed in contact with the inspiring people we met at the Rathenau institute, of whom many were old iGEM judges and/or involved in the Synenergene project. One of them, Virgil Rerimassie is working at the Dutch Ministry of Infrastructure and Environment and invited us for an interview as he was shaping the future legislations on Biosafety in synthetic biology. We shared our view on the current state of Biosafety, the trends and the changes that have to be made to this legislation in order to keep up with the fast developing field of synthetic biology. As we were honoured that our opinion was valued and inspired by this meeting, we decided to invite Korienke Smit from the RIVM and Zoë Robey, a former employee at Rathenau, who was involved in iGEM partner Synenergene, to further explore the risks of synthetic biology in our podcast series.