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Product safety

When developing a product through lab work you have to consider not only the lab safety, but also what implications the product might cause. To discuss the safety risks of our product the iGEM Uppsala team had a safety day during which we sat in groups, discussed and answered questions together.

Safety concerns

So, suppose that our project has been developed successfully, then we have a bacteria that is able to find and kill the pathogen Yersinia selectively. If the bacteria is produced as large scale the risk of mutation increases. If this bacteria mutates, to generate a new variant of bacteriocin, so that it can go around and kill good bacteria it could become dangerous. Since the bacteria leaves our body through feces, this harmful version would easily be spread to the environment without being detected. The larger stocks of bacteria makes possible leaks more devastating.

Even if it doesn’t mutate we will also still have the issue where it can disturb the ecosystem in environments we haven't thought of. Our organism is engineered to work in our intestines and gut but there is a risk that there is some other niches where it could survive. If our bacteria kills Y.enterocolitica effectively in the environment aswell the microbial balance might be disturbed. The microbial ecosystem is still very unknown and therefore larger precursions must be used.

The signal peptide and anchor protein could be used together with something dangerous. Since we’re designing a targeting, sensing and killing system, those systems could be redesigned for malicious purposes. For example improved export peptide might be used to secrete toxins in the environment. For each step towards more complex systems in synthetic biology is a step towards more unpredictable bioweapons.

Precautions

Our project currently doesn’t include any features to reduce risks. We would however, need to to invoke some kind of kill switch if our organism comes in contact with an environment where it is not supposed to be present. Such a switch could be a temperature-dependent-switch. The toilet is seldom 37 dC like the human body. This could make it tricky with culturing, bacteria should be at 37 dC all the time. This might be challenging when freezing and thawing cells, but not unovercomable. Another way could be to make it react to a substance very common in global environment that’s not present our gut and intestines, or the other way around. A third option is to modify the system so that the Bactissiles will start a producing a lysis protein at the same time as they produce the toxin. However this is poor in that it does not stop the bacteria from growing if no Y.enterocolitica is present.

Another important aspect is to have through product control to check for mutations in the system. If continuous mutation checks are done in a broad range screening then mutated toxicology of colicin can be reduced. A frozen stock of the original unmutated bacteria should be kept so cultures can be restarted.

To reduce the spread in nature and effect on microbial ecosystem the advantage of the modified bacteria can be tested with a simple competition test. This should be done routinely to ensure no mutations.