Our Concept
Safety and security are not only central components of our project, but also essential for scientific research in general. In our discussions with Prof. Dr. Alfred Nordmann, expert for history and philosophy of Technoscience, we realized that researchers have a special obligation to act responsibly and consciously. Thus, we are committed to adhere the guidelines of the European Responsible Research and Innovation (RRI) concept. This framework brings us as scientists into interaction and necessary exchange with society. This is especially important in iGEM. Here, everyone strives to change the world with synthetic biology. We do not want to stay in the lab and do science for the books. We want to go out and tackle everyday issues to make the world a better place. Therefore, it is incredibly important to include society into science and make sure that possible solutions do not carry severe issues or risks with them. Since this is of great importance, it is crucial to follow a reliable concept that applies to all aspects of a real world scientific project. Therefore, we have developed a customized Safety & Security concept. It is designed in regards to the framework provided by the iGEM Safety & Security Committee. We have adapted and fit this concept into our own research procedure, which changed our way of progressing in our project.
We have developed a multi-faceted concept which is made up of four key elements. Since we developed this concept at the beginning of our project, we were able to follow this approach throughout all the phases of our work. Thus, we were able to turn our whole project into a mission that aims to increase biosafety in SynBio as a whole. By additionally incorporating genetic safety mechanisms like a kill-switch, we strive to increase the safety of implementation of our project, further on. Moreover, we aimed to involve both experts and the general public in our decision making. This allowed us to gain a reliable safety evaluation and monitoring. Furthermore, it helped us recognize fears and concerns of those for whom we were developing this project: The general public.
Elements of Our Concept
Public Engagement
For Public engagement we adapted the RRI Framework of the European Union. Our aim was to obain permanent feedback and suggestions from different stakeholders for security considerations. One of these groups is the broader society for sharing wishes or fears. Another group was different scientific experts who can provide feedback and insights in the specific field of knowledge. By contacting stakeholders and public authorities, we can additionally ensure that the application of the developed project is not only safe, but also complies with the given biosafety procedures and legislations.
Biosafety & Biocontainment
Unintentional release of biological agents like microorganisms or toxins can bear the risk of harming humans or the environment. Considering biosafety and biocontainment we want to ensure that any effects on humans and the environment are diminished, ideally completely avoided during and after the research process. To achieve this, various strategies can be applied. These have to be considered thoroughly before and during the research. As an example, certain genetic mechanisms can be implemented to enable effective biocontainment, e.g., killing cells at a certain time point or when leaving a certain work place. Thereby, possible harmful effects can be prevented by disabling any form of unintentional release.
Biosecurity & Dual-use Prevention
The aim here is to ensure that our system cannot be misused in any way that would harm humans or the environment. It would be fatal, for example, if our system were not to be used for the proposed implementation but for military purposes. A possibility to use a certain technology for good or evil is called dual-use. Our main approach to achieve biosecurity was to prevent such dual-use. Careful decisions on the used bacterial hosts and the afforded genetic modifications have to be made to reach this goal. As an additional possibility, the technology would only be distributed to customers who are recognized as trustworthy by official commissions to prevent the engineered system from being used as a bioweapon.
Safe Working & Covid-19 Measures
Of course, our concept also includes the safety of our own team members. Conscious research also means acting responsible regarding the researcher’s own health. Normally, this would mainly refer to safe lab work conducted by trained team members in a minimal risk laboratory environment. During the Covid-19 pandemic this was still one of our main concerns but additionally any team work outside of the lab had to correspond to the afforded safety measurements to avoid infections and any further spreading of the disease. Especially during Covid and studying digitally another aspect arises regarding the safety of a team: mental health. In labor-intensive projects as in iGEM mental health needs to be considered and monitored as well. Therefore, we have three team members that are explicitly there for monitoring the people, their behavior and their mental health. This receives too little attention in research projects and we want to change it from the bottom-up.
Impact on Our Project
Human Practices
Our Human Practices work is based on the concept of Responsibility, Research and Innovation (RRI) inspired by Prof. Dr. Alfred Nordmann. In the RRI concept, it is especially important to integrate society into scientific progress.
We have performed a public survey to gather opinions, fears and concerns of the population regarding synthetic biology to realize this. The result of the survey was that only 5% of the participants consider synthetic biology to safe. Whereas, 44% of participants see risks in synthetic biology. Moreover, we received many comments about fears via the free text section. Participants were concerned about misuse, careless handling of engineered biological systems and loss of control when working with these systems. We want to pay attention to these problems and address them in order to reduce fears of the public. Therefore, we have focused on emphasizing safety and security during our project. As a consequence, we talked to several experts about safety. Through our discussions with Dr. Johannes Fritsch, Dr. Michael Vockenhuber and Dr. Swantje Straßheim we gained many insights into this topic. This enabled us to design our project safely as all these experts are having great knowledge in this area.
Project Design
We designed our project in a way that would fulfill our aim to improve the safety of SynBio tools. As explained in our implementation approaches, biofilms are an emerging industrial application because of their outstanding properties. Functional biofilms contain useful and harmless bacteria. However, when used in wastewater treatment it can occur that pathogens invade these biofilms and even conquer them. These pathogens can not only harm the biofilm itself, but also be protected in it. This allows the pathogens to multiply and spread unhinderedly. Since this can cause severe health problems for humans, we want to avoid this spread. Thus, we decided to equip functional biofilms with an additional safety layer. We engineered B. subtilis sleeper cells that are able to sense pathogens and then express a specific bacteriophage that eradicates the pathogen. These sleeper cells are then co-cultured with the bacteria cells of the functional biofilm. Thus, we offer a platform by which biofilms can be applied in a safe way.
Since our platform is based on phage expression, the resulting cell reaction should not have any possible impact on human health, as phages specifically attack only their target bacteria. By this, humans in general and their non-pathogenic microbiomes are safe.
An additional control system has been integrated into the biofilm in order to prevent unintentional release of GMOs when using the biofilm outside the lab. For this reason, we developed a kill-switch, preventing our B. subtilis cells to survive when leaving the biofilm. The survival of the bacteria depends on a signaling molecule which can only be found inside the biofilm. Regarding biosecurity, our kill-switch cannot be misused, as late or reprogrammed activation of the switch will lead to the loss of its functional structure. This will ensure that the modified organisms’ application is limited in space which results in a higher level of biosecurity.
Project Evaluation
Since our project PHIRE BYRD is rather complex, it was important to examine it from different angles and perspectives to ensure that we did not miss anything regarding its biosecurity. Therefore, we talked to various scientists and experts in the field of biosafety and adjusted our project according to their insights. This resulted in our project being under a constant evaluation and development process.
We talked to Prof. Dr. Kathryn Nixdorff, with whom we discussed questions of responsible research, especially concerning biosecurity and dual-use. According to Prof. Dr. Nixdorff’s opinion, our project and its individual components do not contain any intrinsic biosecurity risks. She is not aware of any examples in which phages or B. subtilis have been used as bioweapons. Furthermore, she expressed that it is very challenging to make a non-pathogenic bacterium – such as the S1 organism B. subtilis – pathogenic by genetic modification.
Nevertheless, she suggested the use of so-called suicide genes to obtain an additional level of safety for the release of our sleeper cells. This promoted our decision to use the B. subtilis kill-switch from last year’s TU Darmstadt iGEM Team. Moreover, she advised us to carry out a proper risk management, thus in form of a Risk Assessment. This was realized in our safety form in detail.
As a founding member of the interdisciplinary organization IANUS for peace research, Prof. Dr. Kathryn Nixdorff emphasizes the inclusion of different interest groups in the research process. As a result, she supported our initiative to make RRI a central part of our Human Practices.
We tried to reach people out of the scientific or biological community to take their opinions and feelings into account. Therefore, we conducted a survey and received a lot of feedback about science communication, synthetic biology and genetically modified organisms from our participants. Including their fears and the consequences they anticipated from our project idea. We were able to process all the gathered information and include it into our project design.
All in all, our project was under a constant evaluation not only by ourselves, but also by scientists and the public. This was key to ensure the biosecurity in our project. However, we did not want to stop there. We wanted to help others and especially future iGEM Teams with the knowledge we gathered and wrote “Thinking beyond: A guide for the Evaluation of iGEM projects”. This way we want to contribute to the safety of tomorrows iGEM projects and hope to inspire them to implement safety and security into their project!
Project Work
Over the course of this year’s project, our safety concept affected our way of working as a team as well. Especially, the ongoing Covid-19 pandemic influenced activities massively. We embraced the challenge of committing to our iGEM project while following strict Covid-19 measurements at the same time. Therefore, we developed a safe lab work scheme: Accordingly, not everyone could work in the lab at the same time. Nevertheless, we wanted to allow everyone to gain experience in the lab. The compromising approach was to form teams of 4 people and a supervisor, who changed every week.
The members of the active laboratory group had to test themselves twice a week and it was made clear that any disease symptoms related to the COVID anamnesis should be communicated immediately. In this case, there were plans to isolate the laboratory group to minimize the risk of infection. In the laboratory itself, each member had his own bench, and there was a hygiene concept to minimize contacts. Within closed rooms medical masks had to be worn. A contact success list was also kept.
Of course, we incorporated safe lab practices into our lab work scheme at the same time. This was realized by conducting a safety training for every team member conducted by our secondary PI Prof. Dr. Dominik Niopek.