New European legislation requires detailed molecular characterization of GMOs to document genetic stability. This is the single most important criterion in biosafety risk assessment in terms of concreteness and simplicity. Angela Ryan and Dr. Mae-Wan Ho ask why decades and billions of dollars of investments should have been wasted, when this criterion alone could have exposed the futility of the whole approach.
The new European Directive 2001/18 /EC on deliberate release of GMOs is broadly welcomed by environmental groups and condemned by GM proponents, especially the US, claiming it smacks of trade restrictions and is unworkable. The most significant element in the new Directive, and one that, if strictly implemented, is likely to disqualify most if not all GMOs for environmental release, is the requirement for molecular data documenting that the GMO is genetically stable. The first line of defence against the risks of GMOs is the technical and scientific detail required to characterize the genetic modifi-cation(s), including "genetic and phenotypic stability" and "techniques for detecting transfer of GM material to other organisms".
ISIS and other scientists have been warning for years that GMOs are unstable, and insisting that molecular data documenting genetic stability of transgenic lines must be provided before any environmental release is allowed. Unless the transgenic line is stable, one might as well forget about studying its long term environmental or health impacts. This should be good news for all concerned. It has the potential to simplify approval procedures for biotech companies and to restore transparency and public confidence, for the data can easily be checked by regulatory authorities.
A Belgian research group recently showed how it could be done using Monsanto's Roundup Ready soya. Monsanto's technical dossier, submitted for approval, had claimed that Roundup Ready soya had a single insert with the intended order of genes. The analysis revealed, however, that both the GM construct and the host genome have been scrambled (rearranged), and hundreds of basepairs of unknown DNA has got in as well , which should have caused RR soya to be withdrawn there and then. The procedures are relatively simple and straightforward, and could be applied to any GMO, plant or animal.
How the new Directive improves on the old
The new Directive appears to cast off the permissive mantle of the old, which required minimal risk assessment, no labelling and no monitoring. Under the new rules, all GMOs have to carry the label, 'This product contains GMOs' and traceability from field to plate must be guaranteed (see Box 4). Importantly, post-release monitoring is also required. as well as molecular documentation of genetic stability (see main text).
Directive 2001/18 acknowledges from the outset that the effects of GMOs may be irreversible and thus (precautionary) preventative measures should be taken, in line with the Cartegena Biosafety protocol to the Convention on Biological Diversity. Provisions for public consultation are in place (see Box 2) and on liability, the commission will bring forward legislative proposals before the end of 2001 to cover any damages incurred in all areas of the EU.
Significantly, existing consents under the old Directive 90/220 are to be renewed under the revised criteria of the new Directive. But for GMOs released for any other purpose than placing on the market, there is a potential loophole in the new Directive under the 'differentiated procedures' of Article 7 (see main text).
A comprehensive environmental risk assessment (ERA) is now in place under the new Directive and includes compulsory monitoring plans for cumulative long-term effects on human health and biodiversity (both agricultural and non-agricultural) after release. Member states are obliged to trace and identify any direct or indirect, immediate, delayed or unforeseen effects from GMOs and must ensure resources are secured for such research. Any adverse effects to human health and the environment that may occur through gene transfer from GMOs shall be accurately assessed on a case by case basis. Ethical considerations are also included in biosafety assessment. To improve the efficiency of this framework, the commission will set up a centralised authorisation procedure that includes the lodging of GMO samples for inspection purposes (Annex IV, see Box 3).
Methodology is now being developed in Europe that could ensure specificity, sensitivity and reliability in tracing GM material (see main text). The notifier must provide detailed information on the nature of the vector, the structure of all parts introduced and any carrier or foreign DNA remaining in the GMO (Annex II & Annex III, see Box 3). The expression of the insert must also be well characterised, including information on the developmental expression of the insert during the lifecycle of the plant. Any toxic, allergenic and other harmful effects on human or animal health that arise from the modification must be determined. The genetic stability of the insert and the phenotypic stability of the GMO must be demonstrated, including any changes to the ability of the GMO to transfer genetic material to other organisms and its potential interactions with the abiotic environment. Altered susceptibility to pathogens facilitating the dissemination of infectious diseases and or creating new reservoirs or vectors must be addressed.
The new directive stipulates phasing out antibiotic resistance marker genes by 31 December 2004 (Article 4).
A potential loophole in the Directive exists under 'differentiated procedures' for non-commercial releases. The differentiated procedures of Article 7, in turn, enables competent authorities to make use of 'simplified procedures' of the old directive 90/220. Simplified procedures will apply if "sufficient experience has been obtained on releases of certain GMOs", allowing authorities to "establish the minimum amount of technical information necessary for evaluating any foreseeable risks from the release".
The minimal criteria for 'differentiated procedures' in the current Directive include molecular characterization (Annex V, see box 3). It stipulates that, "information shall be available to demonstrate that any inserted genetic material is well characterized, including the cons-truction of any vector systems or sequences of genetic material used with the carrier DNA". But this could be excluded if the previous 'simplified procedures' were to apply.
GMOs in farm scale trials come under differentiated procedures, and so there is the possibility for the simplified procedures to be applied. However, all GMOs will eventually have to satisfy the requirements of the new Directive before going onto the market. So, what is the point of wasting money investing in GMOs that will only be rejected later on because they fail in the most basic criterion of genetic stability? There is no case for retaining the simplified procedures from the old Directive.
Consultation with the public
Consultation with the public is covered by Article 9, and exchange of information between competent authority and the EC by Article 11. And all the information must be made available to the public for consultation purposes under article 9.
Member states must consult the public and appropriate groups on the proposed release, and make arrangements for this consultation, including a reasonable time-period to express an opinion. The public shall have access to information on all part B releases in their territory, as well as all the information exchanged between the authorities and the commission.
The commission will set up a system of exchange of information contained in notifications. Authorities must send, within 30 days, a summary of each notification to the commission AND to the public for consultation. The commission will then, within 30 days, forward these summaries to other member states.
Perhaps the proponents of GM can't face the awful truth that all GMOs may be genetically unstable . This is confirmed by studies commissioned by the EC itself . A three-year risk assessment at University Blasise Pascal in France and the Max-Planck-Institut für Zuchtingsforschung in Germany, explored mechanisms that contribute to genetic instability in GMOs. It concludes:
"Biotechnology relies to a large extent on our ability to introduce foreign genes into cells. A major problem with present day technology is the non-predictability of the integration of such transgenes. DNA introduced into plant cells mostly integrates at random, i.e. at non-predetermined positions of the genome. The biological process ultimately responsible for random integration is known as illegitimate recombination. DNA integrated at random frequently contains multiply copies and often copies are scrambled. Multiple copies also often induce gene silencing and hence instability in the expression of the introduced genes. In addition, the DNA integrates at loci of unknown stability and capacity for expression of randomly integrated copies may induce unpredictable and undesirable mutations in the host genome we still lack the knowledge for precision engineering of plants' genes." .
The commission also funded research to evaluate horizontal gene transfer from GMOs to the microflora, and in animal gut . (This is another area ISIS has covered extensively, and follows directly from the structural instability of GMOs.) The study notes that the risks of "horizontal gene transfer cannot be excluded", stating, "Free DNA persists in some materials for weeks, and furthermore, some bacteria develop natural/chemical competence to take up DNA from the environment. In addition, in the gastrointestinal tract of man and husbandry animals, DNA may remain stable for some time, particularly in the colon."
Genetic stability is perhaps the single most important criterion in biosafety risk assessment in terms of concreteness and methodological simplicity. It is astonishing that decades and billions of dollars of investments now should have been wasted, when this criterion alone could have exposed the futility of the whole approach. It is high time for all rational GM proponents to abandon ship and cut their losses, instead of continuing to imperil the rest of the world.
There are seven annexes in the new EU directive.
Annex I defines the Directive's scope, which includes all types of GMOs, such as GM animals and GM microorganisms.
Annex II sets out the principles of the environmental risk assessment.
Annex III constitutes the environmental risk assessment proper and is split into to classes.
Annex III A stipulates what is required in notifications for GMOs other than higher plants and Annex III B covers GM higher plants (GMHPs).
Annex IV is additional information required, including details of the nucleotide sequences as well as the methodology necessary to identify the GMO(s).
The commission will establish one or several registers to record information on genetic modification(s), that will help to assist monitoring and inspection.
Annex V details the criteria for the application of differentiated procedures (article 7), which requires the inserted genetic material of the GMO to be well characterized.
Annex VI contains the guidelines for the assessment reports.
Annex VII details a compre-hensive, compulsory, case by case, monitoring regime.
EC traceability legislation
The European Commission's regulations on labelling and traceability of GMfood and ingredients, adopted July 25, require all food and feed derived from biotechnology to be labelled, including highly-processed corn and soybean oils that are now exempt because they cannot be tested for novel DNA or proteins.
The proposals must also be approved by the European Parliament and Council of Ministers, whose approval is expected, but modification is possible.
The traceability provisions would require records to be kept from the farm level on through the production process. The rule includes a 1% threshold for 'adventitious presence' of GM materials in non-GM com-modities.
Producers must be able to show that the traces were "technically unavoidable", and the GM material must have been approved by the EU or an outside country for use in food .
Article first published October 2001