Team:KU Leuven/Human Practices/Ethics/Normative/Biosafety

“Unexpected interactions between synthetic microorganisms and the environment or other organisms produce risks to the environment and public health. These risks have to be addressed in order to use synthetic biology responsibly. Synthetic microorganisms released into the environment could initiate processes of horizontal gene transfer and affect biotic balances, or evolve beyond their functionality and elicit unprecedented side-effects on the environment and other organisms. Synthetic biology products must therefore address bio-safety issues when they have consequences for ecology and human health.” (EgE, Opinion no. 25., 2009)

The first concern we need to address is biosafety. “Unexpected interactions between synthetic microorganisms and the environment or other organisms produce risks to the environment and public health. These risks have to be addressed in order to use synthetic biology responsibly. Synthetic microorganisms released into the environment could initiate processes of horizontal gene transfer and affect biotic balances, or evolve beyond their functionality and elicit unprecedented side-effects on the environment and other organisms. Synthetic biology products must therefore address bio-safety issues when they have consequences for ecology and human health.”(EgE, Opinion no. 25., 2009). As mentioned in this definition, we will now highlight the possible environmental impact and the impact on human health. This can be divided in three topics. The risk of exposure in the lab and its consequences, the containment of the bacteria in the lab and the larger environmental impact. The first two are already well regulated by official lab safety measures and protocols.
It is important to understand that it is impossible to eradicate the risk of escape of a modified organism once it enters large scale production and commercialisation, no matter how rigid the safety measures. This is why we will now review the larger environmental impact on both human health and the ecological system more in depth.

Ecological impact

First we consider the impact of the intended use of our product and the possible consequences of incorrect use, by accident or malice. Therefore extensive and long-term ecological impact assessment studies are indeed required before the release of a modified organism can be authorised as is mentioned by the European Group on Ethics in Science and New Technologies to the European Commission, recommendation No. 4: “The group recommends that before an organism, fabricated or modified by synthetic biology, is released into the environment, ecological long term impact assessment studies must be carried out. Data resulting from such studies should then be evaluated taking into account the precautionary principle and the measures foreseen in the EU legislation (Directive on the deliberate release into the environment of genetically modified organisms). In the absence of a favourable assessment the release of organisms fabricated or modified should not be authorised.” (EgE, Opinion no. 25., 2009). These studies are beyond the scope of our project, but it does not release us from the need to consider the possible impact of our project on the environment after intended use or malpractice. It is impossible to foresee every possible effect of each decision, but any responsible human being should at least consider the possible ramifications of their actions. Thanks to our collaboration with interested parties within the industry we can already obtain a first idea of the effectiveness and possible impact of our project on the environment.
To begin with, there is the intended environmental effect of the project: to reduce our dependence on pesticides and their impact on the ecological system. Pesticides can not only be dangerous to human health (eg the unbridled use of DDT in the past, particularly in North America) but also also have an impact the environment and more specificly biodiversity (Oosthoek S., 2012). Biodiversity is essential for the correct functioning of each ecosystem; a decline in biodiversity has a direct impact on our prosperity as well (Cardinale B.J. et al., 2012). Besides these direct systems there are also long term effects caused by degradation products and the accumulation of waste and other harmful side products (Fenner K. et al., 2013).
For more detailed information about the safety of the compounds our bacteria produce see here .
Besides the intended effect of the introduction of our system there are however potential unforeseen and not intended effects. What could be these effects of the spreading of our system into the environment? Is there accumulation of our products in the environment? Will the introduction of beta-farnesene and methylsalicylate affect insects and or other non-target organisms in a harmful way?
A review of the current knowledge surrounding these questions can be found in the above mentioned link. Further answers can only be attained by extensive field trials. Some of these studies have been done, (James, 2005) (Cui et al., 2012) but only focused on the effectiveness of the pheromone on the intended organisms. They did not study the impact on non-target organisms nor long time effects.
Another important element to consider regarding the growth of our bacteria in nature is the fact that current synthetic biology plasmids use antibiotic resistance for positive selection. The spreading of resistance genes is something that has to be prevented whenever possible. We are investigating the possibility of using a toxin antitoxin system to reduce the chances of horizontal gene transfer.
Further safety measures include creating a positive dependence system via an auxotrophic growth system, physical containment and a kill switch.

Human Health

Another key argument in favour of this project is the positive impact on human health caused by a reduction in the use of pesticides. Pesticides are purposefully designed to kill pests and many of these products can also have an effect on humans.
Possible dangers are both acute poisoning and chronic health effects. The long term health effects can arise as a consequence of an acute poisoning and/or can be caused by chronic exposure. Ample data has been acquired over the years indicating a significant effect of pesticides on human health (CAPE). Exposure has been linked to the onset of, among other diseases, lymphomas, disregulation of the immune system and neurological damage, causing for example Parkinson’s disease (Pezzoli G. and Cereda E., 2013) (Burns C. J. et al., 2013).
For these reasons the reduction of our dependency on pesticides is positive for human welfare. Current regulations in the EU require evidence that there is no harm to people’s health before a new compound is approved (European commission).
Of course the possible health risks of our system have to be kept in mind and examined. The specifications of the volatile compounds produced by our system are E-β-farnesene and methyl salicylate. Possible risks of these molecules can be found here.
Further risk assessments will have to be carried out in accordance to EU legislation before an uncontained product release can be considered. Indirect long-term health-related risks associated with the ecological effects of synthetic biology are hard to predict (EgE, Opinion no. 25., 2009). The matter of what a just balance between precaution and action contains will be discussed later on.