Further drafting of the guidance on risk assessment and risk management of LMOs with stacked genes or traits

Dear all,
AS I go through the draft outline for 'stacked event', the key elements are:
(1). Assessment of the intactness of the inserted loci and genotypic stability (no consensus)
(2). Assessment of potential interactions between combined events and the resulting phenotypic effects
(3).    Assessment of additive, cumulative, synergistic or antagonistic adverse effects of stacked transgenic traits on the conservation and sustainable use of biological diversity in the likely potential receiving environment, taking also into account potential adverse effects to human health.

It is important to determine the stacked events at the genotype and phenotype levels, which are broadly taken care by elements (1) and (2) above. However, it appears that these elements (1 & 2) mainly focus on the stacked genes whereas the likelihood of these stacked genes intereacting with the genome/genetic elements of the receiving organism need to be ascertain as well.

Thank you.

Sincerely,
Dr Kok Gan Chan

Dear Colleagues,
I do not agree that a separate risk assessment guidance document is required for LMOs containing events that have been combined via conventional crossing. The points to consider in the draft document are covered by the existing provisions of the Roadmap.
More specifically:
Point 1
i.   A molecular analysis is typically performed to assess the intactness and stability of the inserted loci. This analysis only provides information that the events are inherited intact. It does not provide any information as to whether the genes are expressing, expression levels or if the desired trait(s) is present. If the gene products are not expressed as expected, the stacked product is unlikely to undergo further development.
ii.  The molecular characterization of the LMO, including multiple transgenes, is provided for in Step 1(c) of the Roadmap. Since this step would encompass stacks created via other means, perhaps it could be expanded to specifically include events combined via conventional crosses.
Point 2
i.   Potential adverse interactions and phenotypic effects resulting from the event combination would be assessed during the development of the stacked LMO. Where these occur, the stacked LMO would not progress through development.
ii.  Potential interactions between events would be identified in the characterization of the LMO under Step 1(c) of the Roadmap.
Point 3
i.   The draft document does not specify if it applies to the combination of events where the parental events have individually undergone risk assessment. If it does, unintentional stacking of events would have already been considered in the risk assessments for the parental events.
ii.  This point is already provided for in Step 1 of the Roadmap, and Step 4(a) could also apply.
Kind regards,
Felicity Keiper

It is useful to provide guidance on what additional information maybe required when considering stacks that contain GM events that have been assessed previously. The routemap already advises assessors to consider the consequences of unintentional hybridisation between an LMO under assessment and LMOs already present in the environment.

The routemap establishes the need for assessments to be carried out in a scientifically sound manner, establishing scientifically robust criteria for the inclusion of scientific information. This needs to be emphasised when considering whether the risks posed by stacked LMOs are greater than the sum of their parts.

Crossing parental lines to combine desired traits is not peculiar to LMOs and should not be considered a risk in itself. There needs to be a rational scientific approach in determining whether and what additional information is required for a stacked LMO in addition to that provided for the single events.

Point 1. Confirming that the insertion loci of the individual events are conserved in the stack and in particular, that they can be detected using existing event-specific markers is a valid consideration. I have discussed the reference to expression levels under point 2(although I agree with Dr Keiper that expression levels cannot be predicted from a characterisation of the insertion loci. If there is a rational scientific hypothesis linking altered expression levels to an adverse effect, information on the phenotype and its impact would be more appropriate).

Point 2:
Altered levels of expression are not a risk per se. Crossing transgenes into different genetic backgrounds will affect expression levels as will growing plants under different environmental conditions etc. Therefore, if elevated/ decreased levels of expression of the transgenes could result in an adverse effect or uncertainty (because levels are outside of the range used in studies such as those involving non-target organisms etc.), this should have been taken into account in the assessment of the single event.

The rationale for 2 is academic, like point 1 it refers to biological phenomena that can occur when crossing plants. The relevance/ context needed to help assessors is absent.

Point 3
Point 2 focuses on interactions between genes and between gene products. A point addressing the potential for an adverse effect to occur as a result of combining the modified traits is needed. Point 3 does not address this adequately. 'LMOs containing stacked events may have altered effects because of additive, cumulative, synergistic or antagonistic effects of the stacked traits'. This statement needs clarification. Examples would be helpful.


Regards

Louise

I would like to contribute some comments from Will Tucker at OGTR,
Thanks
Paul Keese