Introduction
The use of $\MyColi$ in the society does not raise too many questions: genetically modified microorganisms (GMM) are already used daily (and safely) in the pharmaceutical industry.
However, we realized that few people were aware of it, and still mingled GMM with genetically modified crops, which have a terrible reputation in western Europe. Although, $\MyColi$ would be welcomed in the industry, we feared that if for some reason we had to ask the authorization of the public to use $\MyColi$, we would only face fear, incomprehension, and eventually refusal. Since the use of synthetic organisms is an important ethical and societal issue, we think that the general public should be included in the debate. But we also think that it should be properly informed about the nature of synthetic organisms and the way they are used. Hence, we decided to organize several popularization events on the subject.
On the other hand, if we consider the biosecurity issues raised by our project, we can conclude that since $\MyColi$ is only able to improve the production yield of a protein, the main issues that could be raised by $\MyColi$ really depend on the protein of interest (PI) rather than $\MyColi$ in itself. However, one could argue that a $\MyColi$ bacterium that would somehow escape from a bioreactor would not be able to lose its ability to overproduce the PI, which could lead to various pollution of the environment depending on the PI.
As a conclusion, we choose to address two different issues in our human practice: the first is the popularization and the public awareness of GMM in particular; the second is the biosecurity measures that should be taken in order to use $\MyColi$ responsibly.
Popularization events
After discussion within the team and with our friends and families, we decided that the themes of our popularization events would be the synthetic biology, the use of GMMs in research and industry (and the role that $\MyColi$ could play in it), and the means and perspectives of genetic manipulations.
We settled on a kind of popularization event that would bring us a maximal visibility, but that would also allow us to interact with each person individually and collect feedback. It would enable us to ensure that our message was not be misunderstood or oversimplified in the popularization process. We found just that opportunity in the Brussels Game festival.
Biosafety
As mentioned earlier, the main concerns raised by $\MyColi$ depend more on the protein that we chose to produce than on $\MyColi$ in itself. However, $\MyColi$ could compel an escaped recombinant bacterium to produce a PI in the environment, when a bacterium without the $\MyColi$ system would quickly degenerate to stop producing the PI. The risk seems thin, since such an overproducing bacterium would suffer from a clear competitive disadvantage in a wild environment. However it is not excluded that the plasmid containing the $\MyColi$ system, since it benefits from the properties of the TA System, could manage to maintain itself anyway through Horizontal Gene transfer (HGT), at the expend of the wild bacteria it infects.
In the current state of our project, however, the plasmids are maintained through the usual system of antibiotic resistance, since the toxin and the antitoxin are placed on different plasmids bearing different resistance genes. The properties of the TA systems are only used to overproduce the protein, not to stabilize the system in the bacterial population. The system will thus decay quickly if the $\MyColi$ bacteria wander in a wild environment, without any antibiotic.
Furthermore, in the final version of our project (that is, if we have the time to go this far), the toxin gene will be inserted in the genomic DNA of the bacteria, preventing it to ever be lost, and compelling the bacteria to keep the plasmid bearing the genes of the antitoxin and the protein of interest. It will also prevent any reasonable chance of Horizontal Gene Transfer of the $\MyColi$ system as a whole.
If, for one reason or another, the overproduction of a protein did not result in a competitive disadvantage, the inducible promoter of the antitoxin would act as a built-in biocontainment device. Indeed,if one selects in the bioreactor an artificial inducer (that is, an inducer not found in nature) for the antitoxin, the escaped bacteria would have no means to inhibit the toxin and would quickly die outside of the bioreactor.
In conclusion, $\MyColi$ seems to be a safe and predictable system, whose biggest danger would be to be used to produce a dangerous protein. This latter problem has to be addressed on a case-by-case basis, by other institutions than ours.
We have a safety page here too.
|
"
- Université Libre de Bruxelles -
