Lab safety

Before starting our lab work, the whole group was given a safety instruction. It included all laboratory practices as described in the WHO laboratory biosafety manual, such as the hazards and risks associated with different chemicals, decontamination methods and practices as well as prevention of the transfer of genetic material and microorganisms. We have been following these safety protocols throughout the project including wearing lab coats, goggles and gloves. We also received general instructions for using lab equipment.

Project Risk

Our three projects can be graded in terms of Biosafety: NUTRInity-Pick-Up is a complete cell-free system and therefore, no bigger considerations have to be made about spreading organisms into the environment. Using minicells, our project NUTRInity-Provide delivers a chassis which does not contain chromosomal DNA. Therefore, they do not propagate anymore and metabolize only for a limited time to produce nutrients. So, this system does not constitute a risk, either. In contrast to the first two sub-projects, the project NUTRInity-Cut Off contains the use of living and viable cells. These living cells are meant to be used inside the gut and automatically get in contact with the environment, at the latest, when they have left the body.

Using genetically modified organisms outside of a laboratory environment always states a certain risk. To ensure that our CDI cells will not be able to survive after they were used as therapeutic bacteria, we plan to implement a killswitch.

So, we started collecting information about previous ideas from iGEM teams with a similar issue. Browsing through dozens of previous wikis to filter the information we needed, we came to the conclusion that there has to be an alternative. Therefore, our Team searched all wikis from 2011 up to now in order to create a database available for everyone.

We scanned our killswitch database for the construct that fits our needs best. We chose the killswitch designed and characterized by the Wageningen team 2014 as a draft, modified with a single, small change. The basic principle of this killswitch is a toggle switch that activates the toxin only if a certain inducer is present and vanishes again.

To find more information see the wiki of the Wageningen team 2014. We want to replace the promoter responding to Rhamnose by a promoter responding to the ArcA transcription factor. ArcA is part of the ArcAB two component system that regulates the metabolism depending on the level of oxygen. In anaerobic environments, ArcB phosphorylates ArcA and enables binding to DNA acting as activator for gene expression.

Having implemented this killswitch with this slight modification, our bacteria would be able to grow in a laboratory environment without any limitations. After the bacteria would have reached the anaerobic environment of the intestine, the toggle switch flips to a “ready to kill” state. When the genetically modified bacteria then leave the gut and get in contact with oxygen again, the toxin is expressed and the cells will die.

Bioethical considerations

Planning to interfere in the human microbiome, we have thought much about what science is allowed to do and where to draw a line. After endless discussions, we were interested in the opinion of somebody with much more expertise in this field. Therefore, we had an interview with Prof. Dr. Friedemann Voigt, head of the bioethics group of SYNMIKRO, to debate the ethical aspects of our projects.

Q: On the one hand, genetically engineered groceries are considered to be highly dubious and undesirable by our industrial society. On the other hand, we are living at a time characterized by a fast growing population and shrinking availability of natural resources. Is it not our obligation to do research on solutions, free of prejudices, which might improve or even save lives, without excluding possibilities just because we are afraid of genetic engineering?

FV: It is not the case that genetic engineering regarding groceries is denied in general. There are huge regional differences. By international comparison, those reservations are quite distinct in Germany whereas other countries are far less refusing which is a good example of how cultural imprinting influences the perception of scientific innovations. This fact is relevant for the second part of your question as well: Of course, it is a crucial scientific virtue to be unbiased but at the same time it is the duty of scientists to both, declare and justify their work towards the public. This aspect becomes more and more obvious but it still remains a challenging task.

Q: One of our projects could enable us to interfere in the composition of the human microbiome so that we would be able to influence organisms which are responsible for our well-being and are involved in the maintenance of our health. The total number of microorganisms in our body is much larger than the number of human cells but they are probably equally essential for our life. In principle, interference in the microbiome would lead to interference in the natural texture of the human being at the same time. Do you think that there is a risk-benefit ratio which is ethically reasonable?

FV: If there was a formula to solve that, I would give it to you. The absence of such a formula requires the consideration ad hoc.

Q: Although it might take a long time until the described idea leads to genetically optimized humans, it still could be our future. Let us assume, synthetic biology would enable us to improve organisms in a way that facilitates those to be less demanding considering food and water resulting in less environmental burden. This could allow for a more efficient supply for more people on earth. To what extent is such a project ethically-morally acceptable?

FV: For some time past, such questions are summarized and discussed under the heading ‘Enhancement’ in the field of bioethics. This extensive debate does not only consider aspects of synthetic biology but also genetic research, pharmacy and medicine. The transition from the production of health and well-being, including the social and ecological aspects, which you are addressing, to such an Enhancement, is a fluent passage.

Q: In the context of many iGEM projects, the operators have direct contact with genetically modified organisms. We have developed systems which involve organisms producing useful substances which are beneficial for the operators while avoiding contact to the organisms during the whole time. Are those systems ethically more reasonable because of the decreasing risk potential?

FV: I would have to take a closer look at that but as far as I can see, it shows that scientific innovation can not only be instrumental, which stands for the application in favor of the desired product but can also guarantee a safer handling of the product itself. It implements the dimension of responsibility into research in a very novel manner.

Q: Regarding the analysis of risks as well as the ethical-moral assessment, there are two fundamental risk factors: On the one hand, the involuntary spreading of genetically modified organisms, on the other hand, the voluntary abuse of those as weapons. Most research works could be abused sooner or later. Hence, which protection mechanisms should be implemented? Should research be restrictively accessible, banning for example DIY-Bio-research?

FV: You are responding to the so-called ‘Dual-Use’-topic. This topic deals with the possibility to make either useful or harmful use of knowledge which lies within the nature of modern science which is anyone’s property and can get along with different intentions. This is by the way not only concerning modern natural sciences but human discipline and social science as well. Especially, because of the current terroristic and military threats, the Dual-Use-debate has become topically in life science again. I am very reserved in terms of extrapolating the need of scientific restrictions based on those incidents, though. In fact, it shows how important it is to keep an eye on the converse dependency of independent science and liberal, social basic order. Therefore, the integration of a phenomenon like DIY-research into the scientific system depends on how we design the system – an issue which goes beyond science addressing the whole society.

iGEM Marburg - ZSM Karl-von-Frisch-Straße 16, D - 35043 Marburg