Team:Reading/Safety
Safety is of paramount importance in Synthetic biology. People have always had concerns about the impact genetically modified organisms can have on the natural environment and on human health, and this concern rightly extends to the genetic modifications and synthetic functions engineered in synthetic biology. Much thought has already been put into safety in synthetic biology1, and many biosafety measures which can be engineered into cells have been designed2.
However, almost all of the literature on biosafety in synthetic biology focuses on E.coli. Here we shall consider the safety aspect of our project, and our use of Synechocystis sp. PCC 6803.
Our project poses very little risk to human health. Synechocystis sp. PCC 6803 is a safety category 1 organism, and has no known interaction with humans. Several species of cyanobacteria are known to produce a range of toxins, called cyanotoxins, which can be fatal to wildlife and humans3. However, Synechocystis sp. PCC 6803 does not produce any of these toxins4, so is one of the safest cyanobacteria in regards to human health.
Risk to human health due to our proposed modifications is minimal. Many of our modifications target the photosynthetic electron transport chain, or involve knockouts of the terminal oxidase complexes. None of our modifications encode any toxin substances, or any substances harmful to human health.
If the genes we propose to insert into Synechocystis sp. PCC 6803 were to be transferred horizontally into an organism hazardous to humans, for example to a waterborne pathogen such as Vibrio cholerae, there would be few potential dangers. Many of our insertions encode components of the photosynthetic electron transport chain, which certainly would not increase the virulence of such a pathogen. The DNA would probably be ejected from the bacterium which had acquired it after a few generations, as it would confer no selective advantage, and would simply consume the resources needed to replicate and express the gene.
One of our modifications however has the potential to increase the virulence of waterborne pathogens as well as other pathogens. A major step in bacterial pathogenesis is for the bacterium to adhere to and colonise the host. We propose to induce hyperpilation in Synechocystis sp. PCC 6803, by inserting another copy of pilA1, the gene for the pilus subunit, pilin. If this gene was transferred to a pathogenic bacterium, it could increase the virulence of the pathogen by aiding in biofilm formation and adhesion to host cells.
Finally, our inserted genes will be carried on the plasmid pSB1K3, which contains the gene for Kanamycin resistance. If pathogenic bacteria acquire this plasmid, this would produce new strains of antibiotic resistant pathogenic bacteria.
Our project poses more significant risk to the environment than to human health; however the risks are still minimal. If the Cyanobacteria in our fuel cell where to escape into the environment, they could pose a threat to the local ecosystem. If the conditions were favourable, escaped cyanobacteria could cause a potentially harmful Cyanobacterial bloom. This could cause damage to aquatic environments and the local ecosystems that rely upon them.
This is unlikely to occur due to release of our modified strain of Synechocystis sp. PCC 6803. The mutant strains will likely be less fit than the microorganisms, and other cyanobacteria, which they will encounter in the wild, and would likely be out-competed, so a harmful bloom caused by our strain would be unlikely.
The main safety aspect of our project is containment of the modified cyanobacteria. The fuel cell we have designed needs to be robust and impact resistant, as well as water-tight, to prevent any possible contamination of the environment with genetically modified cyanobacteria.
The most appropriate form of in-built biosafety measure we could use to prevent release of our mutant Synechocystis strains is to force dependency on the fuel cell environment. This is achieved by removing the genes for enzymes needed to synthesise important biomolecules, and then providing the biomolecules to the bacteria within the fuel cell. This means that the mutant bacteria are unable to survive outside the fuel cell, preventing any escape or damage to the environment.
- Schmidt, M. & de Lorenzo, V. Synthetic constructs in/for the environment: Managing the interplay between natural and engineered Biology. FEBS Lett. 586, 2199–2206 (2012).
- Wright, O., Stan, G.-B. & Ellis, T. Building-in biosafety for synthetic biology. Microbiology 159, 1221–1235 (2013).
- Stewart I, Seawright AA, Shaw GR (2008). "Cyanobacterial poisoning in livestock, wild mammals and birds – an overview" Cyanobacterial Harmful Algal Blooms: State of the Science and Research Needs. Advances in Experimental Medicine and Biology 619: 613–637.
- Sinonen K and Jones G (1999) "Cyanobacterial Toxins" In Toxic Cyanobacteria in Water. Chorus I and Bartram J (eds): 41-111. WHO, Geneva.
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