Team:UCL/Project/Xenobiology
From 2014.igem.org
The ultimate biosafety tool
(Xenosummary work in progress)
“Any technological advance can be dangerous. Fire was dangerous from the start, and so (even more so) was speech - and both are still dangerous to this day - but human beings would not be human without them.” - Isaac Asimov
Since the early days of genetic engineering, our ability to manipulate living organisms had to face the invevitable risks of any new technology. Each advantage brought by technology is tightly linked to its risks, many of which we cannot predict.
Since we cannot predict all the possible dangers of a new technology, as scientist, we have the responsibility to implement all the safety measures to cover the known risk and speculate on the level of safety we want to achieve in order to moderate the unknown risks.
The Asilomar conference first addressed these concerns, and set limits to the work of scientists. Research in Synthetic Biology has brought these concerns to a new level: as our tinkering with Biology increases, the unknowns of this technology expand and oblige us to further reflect on the safety measures we need to implement.
Biosafety strategies have so far explored biology to implement clever mechanisms to control this technology. They investigated various strategies that allow to kill bacteria when needed or that hinder genetic information to spread among different organisms.
Our biosafety strategy is exploring the regions outside of Biology, with the ultimate goal of bringing Biology to a parallel domain where it does not interact with our own one. Why tinkering with our same Biology when we can create a new on, at the same time biology and technology, that we can control at a much higher level?
Xenobiology is the part of synthetic biology that implements the term "synthetic" by creating organisms that are unable to survive in the natural environment and necessitate an artificial intervention from man to exist. Xeno definition...
Biosafety in Synthetic Biology
The wide use of genetically modified organisms causes concerns on how they will interact in the natural environment. In particular could the genetically modiefied microbes escape our constrains, and outcompete the organisms found in the natural ecosystem? Could the DNA we inserted into a specific bacteria be transmitted, with unknown spread of information?
Leak of Bacteria
Containing engineered microorganisms has been the main concern of genetic engineers.The leak of any form of life into a new environment could destabilise the environment, and the same problem applies to synthetic forms of life. Any new organism could outcompete the natural species and undermine the equilibrium of an ecosystem.
Physical containment can be addressed with auxotrophic strains, sterilisation of tools and materials used in experiments together with a conscious waste disposal.
Nevertheless, as the image shows, the possibility - even if remote - of an accident is always present and any biosafety measure should take into account the worst case scenario.
Leak of DNA
The leak of bacteria is not the only risk involved in the use of GE organisms. The information encoded into the GE is new and has been artificially designed for that specific microorganism. We assume that it will not have any other effect than the ones we predicted, but we also have to remember that our knowledge is limited and we moderate any unknown risk.
DNA can also leak from the microorganisms and it is possible that other bacteria can take up that information and start behaving accordingly. We could give a selective advantage (e.g. antibiotic resistance?) to some specific bacteria and our control over the consequences would come close to zero.
Even if the evidence for leak of GE strains of bacteria shows that they are strongly disadvantaged in the natural environment, we don't know how the spread of DNA could affect other species, in particular as the level of engineering becomes higher and higher.
Biological vs. Xenobiological strategies
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Biological strategies
- Restriction enzyme systems
- Semantic containment e.g. amber codon
- Suicide system e.g. toxin/antitoxin
- Auxotrophy
Xenobiological strategies
A safety mechanism embedded into the system on three different levels
- Genetic Firewall
- Semantic Firewall
- Metabolic Firewall
Reference:
- Wright, O., Stan, G.-B., and Ellis, T. (2013). Building-in biosafety for synthetic biology. (Review) Microbiology, 159, 1221-1235. http://www.ncbi.nlm.nih.gov/pubmed/23519158
- Okada, K., Minehira, M., and Zhu, X. (1997). The ispB gene encoding octaprenyl diphosphate synthase is essential for growth of Escherichia coli. Journal of Bacteriology, 179, 3058–3060. http://www.ncbi.nlm.nih.gov/pubmed/9139929
- Søballe, B. , Poole, K. R. (1999). Microbial ubiquinones: multiple roles in respiration, gene regulation and oxidative stress management. (Review) Microbiology, 145, 1817-1830. http://www.ncbi.nlm.nih.gov/pubmed/10463148
- Schmidt, M (2010). Xenobiology: A new form of life as the ultimate biosafety tool Bioessays, 32, 322-331. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2909387/
- Malyshev, D.A., Dhami, K., Lavergne, T. et al. (2014). A semi-synthetic organism with an expanded genetic alphabet Nature, 509, 385-388. http://www.nature.com/nature/journal/v509/n7500/full/nature13314.html