The Cartagena Protocol on Biosafety

At the international level, the Cartagena Protocol for Biosafety (Bail et al., 2002, hereafter referred to as the Protocol) came into force on September 11, 2003, 90 days after the fiftieth instrument of ratification had been deposited by signatory countries to the Convention on Biological Diversity (CBD). The Protocol is the most important single international treaty, and will play a dominant role in shaping the future of transgenic technology in the world. It is the first legally binding international regulatory framework for the transboundary movement of living modified organisms (LMOs). The need to have an international regulatory framework for GM organisms was discussed by countries during the drafting of the CBD, which was adopted at the 1992 Earth Summit in Rio de Janeiro. At that time, the first GM crops were coming to the market in the USA, and their use would increase exponentially during the following years. In the final document, the CBD did not specifically address biosafety, but Article 19 called for the signatories to consider the ‘need for and modalities of a protocol setting out appropriate procedures, including, in particular, advance informed agreement, in the areas of the safe transfer, handling and use of any living modified organism resulting from biotechnology that may have adverse effect on the conservation and sustainable use of biological diversity’.

The international community will need time to gain experience as to how the various instruments and mechanisms of the Protocol can operate effectively to ensure the safe transfer of LMOs from country to country, taking into account biodiversity considerations. In carefully worded language, the Protocol obviates antagonism with national regulatory frameworks, by explicitly giving precedence to national standards regarding the safety assessment of LMOs, and in this sense does not lay any claims to standard setting. Parties are sovereign under the Protocol to have their own national standards. What the Protocol brings forth is a set of ideals or socio-ethical endpoints that parties should consider in deciding about LMOs and their applications, particularly concerning a precautionary approach, sustainable development and the conservation of biological diversity.

One of the Protocol's goals is to serve as a minimal baseline regulatory framework for countries that do not yet have domestic frameworks. The Protocol distinguishes three types of LMO applications: for food, feed or processing (LMO-FFP); for either contained use or for intentional introduction into the environment. For LMO-FFP and contained use with LMOs (Article 18), parties are obliged, under the Protocol, to inform the other parties of their decision regarding transboundary movement, but domestic standards and regulations prevail for the approval process. On the other hand, LMOs intended for introduction into the environment, for example, as seeds, are subject to the advance informed agreement (AIA) procedure of the Protocol, applicable to the first transboundary movement. As such, the Protocol is both product and process based. According to the AIA, the party of export must notify the competent authority of the country of import, prior to the first transboundary movement of the LMO. The exporter is required to supply the party of import with all necessary information regarding the LMO, including a risk-assessment report and the regulatory status of the particular organism in the exporting country. Within 270 days after the receipt of notification, the party of import communicates, in writing, to the exporter and to the Biosafety Clearing House (BCH) on the decision it has taken. The AIA procedure is meant to prevent an uncontrolled dissemination of LMOs, for example, in developing countries that do not yet have the appropriate biosafety framework for regulating these products.

An ambiguous case for the regulation of LMO-FFPs would be the import of grains as food by farmers in developing countries that do not have domestic regulatory frameworks, particularly when the grains could also be used as seed material. The solution put forth in the Montreal negotiations of the Cartagena Protocol was to make reference to the precautionary approach and to require precise wording ‘not intended to be used in the environment’ on the accompanying documentation (Article 18.2a). If a domestic framework does not exist, developing countries or countries with economies in transition can indicate that the final decision will be taken according to a risk assessment undertaken in accordance with the provisions of the Protocol and within a predictable time frame.

There is also an information-sharing aspect included in the AIA procedure, since the party of import is required to communicate with other parties through the BCH. In addition, the party of import may also request the opinions of independent biosafety experts or seek out further sources of information. The BCH is, therefore, the main information-sharing mechanism of the Protocol and is meant to assist parties in its implementation. It is an Internet-based platform for the exchange of scientific, technical, environmental and legal information about LMOs at national, regional and international levels. Information available in the BCH includes contact information for national competent authorities, rosters of biosafety experts, and risk-assessment reports, as well as national decisions regarding the import of LMOs (www.biodiv.org).
The Cartagena Protocol is a de facto trade agreement, since its scope includes export and import activities. The Protocol could be positive for trade: trade rules would be clearer with AIA; trade could be fairer; scientific risk assessment would be used systematically for decision making and a basic, operative regulatory framework for LMOs would be available for countries without domestic regulations. Seed companies would benefit from a system with mutual acceptance of safety evaluations and science-based risk assessments (de Greef, 2000). The Protocol is a decentralised approach that recognises national standards and allows them to be more restrictive. At the same time, and as the Preamble states, the Protocol is not subordinate to other international agreements and its implementation should work in accordance with them.

National and International Frameworks for the Safety Assessment of Transgenic Crops

The controversy regarding GM crops has less to do with their scientific safety assessment, which demonstrates that these crops are at least as safe as their conventional counterparts, than with the wider social, political, ethical and economic endpoints related to their commercialisation. As a result, national regulatory frameworks for the authorisation of GM crops often combine science-based risk assessments with public policy. The word ‘biosafety’ has come to denote the entire process of coming to a decision about the safe use of biotechnology products. Alternatively, Wolt and Peterson (2000) call the process of considering both scientific and social issues ‘risk analysis’ to distinguish it from risk assessment, which considers only technical risks. Applied to GM crops, this means that the consideration of potential export markets for these products would belong to the wider risk analysis, while the consideration of outcrossing with native species would belong to the technical risk assessment. Widening the risk discussion to include alternative framing of risk, such as the availability of export markets, invites public debate regarding the wider impacts of applied technology, such as political accountability, equity, ethics and economics. ‘Public debate is a way of isolating what is strictly scientific from what is socially or politically determined in the development of scientific activity’ (Touraine, 1997).

National regulatory frameworks for GM crops are all alike, in that they seek to ensure an adequate level of protection for human and environmental health, based on the best available science. There is general agreement, for example, on the characterisation of donor and recipient organisms, environmental impact assessments and toxicity issues. On the other hand, national regulatory frameworks can also be diverse, depending on the basic assumptions about the novelty of using recombinant DNA techniques to modify plants. The margin separating natural from unnatural gene modification certainly exists but, because traditional plant breeding also involves the transfer of genes, on a scale that is magnitudes greater than during the genetic engineering of plants; it is less tangible than we would wish it to be. An important distinction must be made, in that there is both a need and a desire to know the kind of regulatory data requirements for risk assessment. Requesting unnecessary (nice to know) data will only add to the cost of technological development of transgenics, which in most cases is already becoming prohibitive.

Where gene modification is considered inherently safe, regulations tend to be product based, and only the final product is assessed, not the process that produced it, as in the United States. In almost all countries, the regulations governing transgenics are process based due to the fact that the organisms have been developed using modern genetic engineering techniques. Whenever gene modification is considered inherently dangerous, regulations are likely to be process based, and the trigger for regulation is the process itself. Adopted in February 2001, European Directive2001/18/EC, on the deliberate release of GM organisms, repealed Directive 90/220/EC as a comprehensive regulatory framework for environmental applications of GM organisms and their commercialisation. In both directives, regulations are process driven, since all ‘plants obtained through the techniques of genetic modification’ are subject to regulatory approval. Genetic modification in the Directive is understood as ‘the introduction of new combinations of genetic material by the insertion of nucleic acid molecules, the direct introduction of heritable material prepared outside the organism, cell fusion or hybridisation techniques’. In the US regulatory system, risk assessment for the environmental release of GM plants examines the likelihood of a GM plant to becoming a pest (7CRF340), based on the assumption that it has the potential to become one due to the presence of genetic elements from defined plant pests (CRF340.2). For example, the 35S promoter from cauliflower mosaic virus or regulatory elements from Agrobacterium used to transform plants. The Canadian approach, which is both product and process based, regulates both GM and conventional plants provided they ‘demonstrate neither familiarity nor substantial equivalence to those present in a distinct, stable population of a cultivated species of seed in Canada PNTs [plants with novel traits] include those derived from both recombinant DNA technology and plants derived through traditional plant breeding’ (Regulatory Directive Dir 94-08).

Risk Assessment of Transgenic Plants

The safety and economics of transgenic organisms in agriculture are critically important issues for both consumers and agricultural producers (Herdt, 2001). In spite of the impressive amount of evidence that transgenic organisms, commonly referred to as genetically modified organisms (GMO), are as safe as any of the other varieties of crop plants that have been introduced in the history of agriculture (Thomas and Fuchs, 2002; National Research Council, 2000, 2002a, 2002b), there is still a great deal of undue political pressure to regulate them increasingly stringently, that are costly and do not add any appreciable value to the safety concerns warranted by any reasonable risk assessment. Scientifically sound risk assessment can allay most of the concerns of the public and instil confidence, but the public has been confused by a campaign of fear and misinformation that is turning out to be detrimental to scientific progress. Transgenic crops, and the biotechnology that produces them, have enormous potential to solve many of the intransigent problems of modern agriculture, conserve natural resources and protect the environment, yet in many countries, the whole technology has been bogged down in a regulatory quagmire.

Ever since Rachel Carson's Silent Spring (1962), citizens of the industrialised world have become extremely concerned about hazards of technology and have created new sets of institutionalised mechanisms to control technology. This has seriously affected the way technologies are designed and developed (Kates, 1986). Irrespective of the ideological differences between the various stakeholders in biotechnology, it is now generally accepted that biotechnology will be regulated and that society will have to bear the costs of such regulation. To a large extent, the public interest groups and activists will influence the development of biotechnological regulation, and this is already seen in Europe, Africa and Asia. An important goal of risk assessment is the minimisation of surprises and plan for risk management. It has to be acknowledged, of course, that ‘surprises’ will persist, but adequate risk assessment should help us manage those surprises and mitigate them.

It is just over a decade and a half since the first transgenic tobacco plants were field tested in the United States in 1986, and the basic principles of assessing the environmental and biosafety risks of transgenic plants have not changed very much since then. The basic question addressed has always been the variety of interactions that a given organism might have with the environment into which it is introduced over a finite period of time. The essential problems addressed are the nature, characteristics and identity of the organism being introduced, together with its persistence and likely impact on non-target organisms. These questions are basically addressed by using the formula:

Risk: Exposure x Time

This formula is derived mostly from chemical and radiation technologies. Risk assessment of transgenic plants continues to evolve. However, it is getting more and more influenced by societal and economic concerns rather than real-world biosafety considerations. As a result, it is not only becoming unduly burdensome but is also hindering biotechnological development and transfer. The standards' bars for biosafety and environmental safety are now being raised on the basis of perceptions of risks rather than real risks, and this is making transgenic crops one of the most expensive technologies. A conservative calculation by one of us (S.S.) estimates that the regulatory review process is costing US $8–10 million for a single transgenic variety to be brought to the market place in the United States, and about $15 million in the European Union. Additional costs for maintaining full regulatory compliance in different countries of the world will also accrue, and these cannot be reasonably estimated at the present time. These enormous precautionary expenditures are undertaken by the developers of transgenics in order to avoid huge penalty costs, to the tune of millions of dollars, such as those that resulted from the StarLink episode (2001) and the ProdiGene Affair (2002). Biotech industry is now engaged in a laborious regulatory compliance process that is going to add to the cost of product development to the tune of millions of dollars.

Most risk assessments proceed from known to the unknown, starting with an excellent scientific background of the crops in question. There is copious information available on the basic biology, reproductive habits and agricultural requirements and husbandry of the majority of the food crops in the world. This background information provides workers with the confidence to take the deliberate and carefully considered steps necessary to introduce transgenic crops into modern agriculture. Yet, there is now such a widening gulf of misunderstanding between the practitioners of modern biotechnology and agriculture and non-scientific people that there no longer seems to be any chance of reaching a consensus. The basic concern of the opponents of transgenic crop technology is that no one can understand the long-term effects of these transgenic crops, and that, if something terrible were to happen, no one would be able to recall them from nature again, and, further, they have the potential to destroy valuable biodiversity, thereby causing untold environmental damage to the planet (National Research Council,2002a, 2002b). Some of the other issues that surround the risk-assessment process are threat to biodiversity, gene transfer into wild and weedy relatives of cultivated plants, increased weediness or evolutionary ‘fitness’, the compromising of plant defence systems, increased resistance by pest species, human health-risk issues, such as the use of antibiotic marker genes, allergenicity and toxicity, and contamination of human and animal food-chain by plants producing biologically active pharmaceuticals, drugs, vaccines and industrial compounds (Gaff and Newcomb, 2003). People are also concerned about the use of genetic user restriction technologies (GURTS), which in the opinion of some will rob poor farmers of the ability to save seed for future planting.

Risk communication has therefore become a central aspect in gaining public confidence about agricultural biotechnology. This critical challenge needs to be addressed by the scientific community in order to overcome public apprehensions about transgenics. In this context, it needs to be emphasised that, whatever scientific risk assessment is carried out on transgenic organisms, the results of this research must be communicated in a simple and easy-to-understand form while remaining accurate. A risk-assessment document is primarily aimed at the general public who may or may not have the necessary scientific background, but is nevertheless concerned about the issues at hand.

Another critical aspect of the risk assessment of transgenic crops is the policy imperative that triggers the development of rules and regulations and lays down the basic principles upon which transgenic organisms are evaluated. A sound scientific policy is the only instrument that can promote the development of standardised risk-assessment procedures based on existing knowledge on a case-by-case basis. When the pathway of regulatory-policy development in most parts of the world is examined, it is usually found that it has been driven by the politics of compromise, which has resulted in a plethora of non-harmonised rules and regulations, executive decrees and guidelines, devised by committees with people who may have had little or no understanding of agriculture, biotechnology or environment and safety issues. The process is thus driven by political expediency and compromise, with science taking a back seat. This has resulted in highly expensive, poor-quality risk assessments that cannot assuage the feelings of the public about biotechnology. It seems likely, therefore, that transgenic organisms will be caught in this type of regulatory quagmire for some time to come, unless science-based risk assessments and risk management procedures are used to provide