Since our project aims to integrate GMOs into food, we were considering how it will be accepted in the market. To answer that, we have arranged a video conference with three officers from the Directorate-General for Health and Food Safety (DG SANTE) of the European Commission (EC).
We learnt that our biosensor would be considered a category 4 genetically modified microorganism (GMM) and to gain authorisation to use GMMs they must be contained. This lead us to re-consider the possibility of developing our Listeria detection test as an isolated cell detection system using Escherichia coli rather than an integrated test using Lactococcus lactis.
We would need to design future tests to prove that our biosensor would not produce false negatives to be accepted by the EFSA risk assessment.
The summary below, relating to both information gained during this exchange with EC officers and our own ideas on the project, represents solely our views and cannot be regarded in any way as the official position of the European Commission.
On the 14th September, we had the opportunity to speak to three officers from the Directorate-General for Health and Food Safety (DG SANTE) of the European Commission (EC). This EC department is responsible for EU policy regarding food safety and health and for monitoring the implementation of related laws. Two policy officers in the Biotechnology Unit, and one Policy Officer on Food Additives kindly agreed to discuss the regulatory framework that our project would have to comply with, to incorporate GMOs into food.
Under current EU legislation, to be authorised for placing on the EU market, all genetically modified food and feed must be authorised under Regulation (EC) 1829/2003 and subject to a risk assessment conducted by the European Food and Safety Authority (EFSA), to assess their safety for human and animal health, and the environment. Our biosensor would be considered a category 4 Genetically Modified Microorganism (GMM), as our biosensor will contain a GMM with newly introduced genes and capable of replicating. When a GMM is to be used under containment, it must comply with Directive 2009/41/EC. This lead us to consider the possibility of developing our Listeria detection test as an isolated-cell detection system using E. coli rather than an integrated test using L. lactis. This would mean a cheese maker could take a sample of their cheese and add our Listeria detecting E. coli and see if there was a colour change.
To be authorised for use in the EU market, our biosensor would need to be thoroughly risk assessed, traced, labelled and monitored. We would need to submit a dossier containing all the relevant information about the biosensor, following the legislative framework (Regulation (EC) No 1829/2003 and Implementing Regulation (EC) No 503/2013), and following EFSA guidelines as detailed here: https://www.efsa.europa.eu/sites/default/files/consultation/gmo101129%2C0.pdf
Around 10-15 applications for GMOs to be used as food or feed are submitted every year. Once EFSA receives the application, it takes a minimum of six months for EFSA to carry out a risk assessment and publish an opinion. However, the process is likely to take longer as, if EFSA needs more information from the applicant, the six-month time period is accordingly extended. In our view, this will imply that in order for our biosensor to be proven safe, it would likely take some time before it could be fully authorised into the cheese making process.
We consider that the accuracy of our biosensor could be another consideration when determining whether it can be used to make food sold in an EU market. False negatives could pose a serious risk particularly to the immunosuppressed who could eat a cheese that failed to turn purple in the presence of even small numbers of Listeria. This is a possibility that we could neither confirm or deny at this stage as it could only be confirmed through rigorous scenario-based testing of our biosensor. However, we decided to try and model the amount of AIP molecules (hyperlink to parts) required to be present in the cheese in order for our sensor to detect a Listeria contamination (hyperlink to modelling page). This should give us a general idea of how reliable our system would be and the likelihood of false negatives.
In our view, false positives, on the other hand, whilst posing a lesser risk to consumer health, may lead to substantial financial losses, and to our knowledge, the amino acid sequence for agrD (the gene encoding the signalling molecule we wish to detect - https://2018.igem.org/Team:Manchester/Parts) is not unique to Listeria monocytogenes. Listeria innocua and Listeria welshimeri, two non-pathogenic strains of Listeria, have identical sequences for the AgrD protein. Despite this, the precise structure of the non-pathogenic Listeria’s AIP has not been determined, and it is possible that after being circularised and modified by AgrB, the non-pathogenic Listeria AIP may not have the correct structure to trigger our biosensor. With more time we would have ideally liked to isolate the AIP molecule from other Listeria strains and introduce it into a culture containing our biosensor to determine the likelihood of false positives.
Once gaining approval to enter the EU market, a GMO for human or animal consumption must be clearly labelled and be traceable to its origin. The traceability and labelling obligation do not apply only when the presence of the GMO is adventitious or technical unavoidable and is below or equal to a 0.9% threshold. The EU law ensures freedom of choice when it comes to GMOs once they have been assessed as safe by EFSA. Any new GMO is given a unique identifier of a fixed length of 9 alphanumeric characters, the first 2 or 3 identify the applicant, the following 5 or 6 designate the transformation event details and the final character is for verification. We also learnt about an interest in using artificial DNA markers with a unique sequence to be added for traceability purposes.
Following our initial inquiries about our biosensor, any application to introduce a GMO into the European market requires that the applicant is established or has a representative in one of the EU member states.
Based on our own analysis, with regards to UK law, recent publications infer that the Secretary of State for Environment, Food and Rural Affairs, Michael Gove believes UK law may change after Brexit to accommodate more freedom for GMOs.
Despite this the Department for Environmental, Food and Rural Affairs (DEFRA), website still states that existing EU regulations will be adopted in UK law . For our project, either outcome may provide added difficulty in the development of our biosensor in the UK or within Europe, so in the future we may have to look elsewhere if we wish to continue the development of our project.