Safety in Agricultural Biotechnology:  1^st International Fresenius Conference

 

Gwilym Williams, General Manager, National Agricultural and Veterinary Biotechnology Centre, University College Dublin, Belfield, Dublin 4, IRELAND.

 

Abstract

The debate about genetically modified (GM) crops has recently matured within the EU to involve a detailed consideration of the potential environmental effects of transgenes.  In early 2002, a workshop organized by Academy Fresenius and entitled ‘Safety in Agricultural Biotechnology’ (Maritime Rhein-Main Hotel, Darmstadt, Germany, February 28^th to March 1^st 2002;  www.akademie-fresenius.de) focused on the dichotomy that currently exists between molecular biology and a new eco-biology, and served to emphasise the urgent need to reconcile these two disciplines. Crucially, the meeting highlighted that science cannot yet provide unequivocal answers to such questions as the potential for environmental gene flow, making it likely that resolving such risk uncertainty with the ‘precautionary principle’ will remain a focus area for some time to come. Such issues were debated by a surprisingly small gathering of about 20 attendees (75% from industry), along with an international panel of 19 speakers. Europe now faces the stark reality that GM crops are a significant and increasing component of global agri-business: there are signs that the debate on the hypothetical safety aspects of these products will soon be superseded by a more directed, agri-economic perspective that will centre on the question of the need, extent and extra cost of GM monitoring and product segregation.

Conference venue: Maritime Rhein-Main Hotel, Darmstadt, Germany

 

 

 

Status Quo in Germany

Heinrich Sandermann (Institute for Biochemical Plant Pathology at the GSF Research Centre for the Environment and Health GmbH, Germany) opened the conference with an explanation of basic plant genetic transformation principles,  providing a provocative critique of current GM risk assessment methods, and championing the ‘ecological genetics’ cause.  In a presentation that assembled reports from a wide body of literature, both scientific and popular, he asserted that risk assessment of GM plants in the US has often been flawed and has lacked a scientific basis; he further contended that a major problem has been a failure to show sufficient cognisance of the potential pleiotropic effects of transgenesis. 

 

Sanderman went on to advance the central thesis that existing environmental selective pressures could be a potential cause of horizontal gene flow from such new crops. He castigated the US government for allowing what he considered to be the premature commercialisation of transgenic crops in 1994. Experimental data detailing the soil stability of genes for novel traits (BASTA^®, 7 – 8 months) and antibiotic resistance markers (kanamycin; 2 – 6 months), were combined with hypothetical risk scenarios involving gene uptake by pathogenic bacteria (under the selective pressure of antibiotics from such sources as animal manure). Citing a Swiss study which showed that manure from animal production units contained antibiotic concentrations in the 50 micromolar range (reportedly representing approximately twice the levels reported in the USA), he emphasised that environmental selective pressures for antibiotic resistance genes were already present in Europe.

 

Sandermann asserted that the escape of transgenes by pollen transfer to wild relatives has long been denied. However, he raised concerns about this issue, drawing on the recently reported putative introgression of transgenes into wild maize in Mexico. His assessment of the economic benefits of GM crops to farmers was also somewhat equivocal. In closing, he highlighted measures to be taken to delay the development of resistance, such as the phasing out of antibiotic resistance genes, herbicide rotation regimes and refuge strategies.

 

Joachim Schiemann (Federal Biological Research Centre for Agriculture and Forestry, Braunsweig, Germany) reviewed the projects initiated under the German Federal Ministry of Research and Education (Bundesministerium für Bildung und Forschung – BMBF), Biotechnologie 2000 scheme, which are aimed at the study of GM plants in the agro-ecosystem.  With a budget of 16.5 million Dm in 2001, and focusing on 9 cluster projects, the scheme is investigating areas such as the targeted transfer of minimized transgenic DNA sequences with optimised function (incorporating elimination of marker genes and limitation of spreading capacity), examination of the potential environmental impact of planting transgenic rapeseed, field research on GM potatoes, monitoring of Bt corn and communication management in biosafety research.

 

Strategies being pursued for the elimination of marker genes include independent co-integration after Agrobacterium-mediated transformation (in barley), the use of the N-acetyl-phophinothricin-deacetylase gene as an inducible negative selection marker, and also the transient expression of bacteriophage P1 Cre recombinase. Further selection systems under investigation include those based on the 2-deoxyglucose 6-phosphate phosphatase gene (DOGR1) from yeast, and also a new putative marker for selective regeneration of plant cells based on palatinase (which hydrolyzes palatinose into glucose and fructose). Additional work is looking at more efficient systems for achievement of site-specific integration of transgenes into plant genomes, triple helix-forming and bifunctional oligonucleotides as new tools for in situ modification of plant genes, and strategies for limitation of spreading capability based on plastid transformation.

 

Schiemann reviewed these topics in the context of the new EU Directive 2001/18/EC, which introduces an obligation for notifiers to implement environmental monitoring plans.  He pointed out that such schemes will need to be developed on a case-by-case basis, taking into account the environmental risk assessment, the modified characteristics specific to the GMO in question, its intended use, and the ‘receiving’ environment. 

 

Focusing on the work within Schiemann’s own cluster, he forecast the requirements of the next generation of GM plants in the context of the characteristics of the EU market, and also the recommendations of the Advisory Committee on Releases to the Environment (ACRE; (www.defra.gov.uk/ environment/acre/bestprac/guidance/index.htm). Firstly, such ‘second generation’ plants should be adapted to specific growing regions, delivering a high yield and showing resistance to specific pathogens. Furthermore, the elimination of antibiotic resistance marker genes, and other transgenic sequences that are no longer of use is vital, while tissue and condition-specific restricted  expression of genes according to needs is also required.  The logic in minimizing transgenic DNA is obvious:  for subsequent transformation, the use of the same selection system is not precluded, while accumulation of marker and regulatory sequences is also avoided, and regions of transgene homology which could result in transgene instability are minimized.  He also called for the production, testing and trade of new transgenic plants to be effected according to consumer demands, and offering as much transparency as possible:  Schiemann outlined that the current credo within Germany regarding the safety of GM plants is “not as good as necessary, but as good as possible”. 

 

Bernd Hommel (Federal Biological Research Centre for Agriculture and Forestry, Kleinmachnow, Germany) reviewed the early results from a BMBF Biotechnologie 2000 project which is comparing the performance and ecological interaction of transgenic potato lines (in which carbohydrate metabolism has been modified) with conventional varieties.

 

Hommel began by reviewing transgenic potato research to date, indicating that the majority of modifications have occurred in the areas of altered carbohydrate metabolism (usually starch), insect resistance (Colorado Potato Beetle, CPB), virus resistance (Potato Leaf Roll Virus, PLRV; Potato Virus Y, PVY) and herbicide tolerance (glyphosate).  Within the EU, about 11% of all transgenic field trials have been done with potatoes (after corn, oilseed rape and sugar beet). In Germany to date, there have been 138 applications for GM potato field trials approved under the existing 90/220 Part B Directive, with 2 applications pending for approval. In the US, 5 approved events are on the market. Hommel stressed the dearth of ecological evaluation research on transgenic varieties. 

 

Hommel’s research group are investigating the possible effects of formation/accumulation of new carbohydrates in potatoes, and the implication for performance (phenotype and susceptibility to pests and diseases). They are also interested in whether genetic transformation changes the potato’s survival potential and invasiveness, and on whether other interactions may be encountered with the environment (such as potential ecological risks from the direct and indirect changes in the potato’s genome with the rhizosphere and pyllosphere). Examination of the most suitable methods for monitoring the cultivation of transgenic potatoes is also an aspect of the project. The Agrobacterium-mediated potato transformants (single and double) constitutively express the artichoke (Cynara scolymos) enzymes, sucrose:sucrose: fructosyltransferase (SST) and fructan:fructan:fructosyl-transferase (FFT), and are therefore able to synthesise fructans in leaves and accumulate them in tubers:  kestose and nystose in SST-lines and high molecular weight inulin in SST/FFT-lines.  These events feature two marker genes – nptII and hph. 

 

The first floral results have found that main shoot length was dependent on seed-tuber weight:  SST/FFT-lines differed significantly from SST-lines with similar weights.  Additionally, the number of all eye-shoots per tuber varied according to seed-tuber weight, and the number of side shoots depended on the length of the main shoot. In the case of the number of flowers per main shoot, the SST/FFT lines differed from others, but in terms of yield, there was no difference found between lines and varieties.

 

Detlef Bartsch (Aachen University of Technology, Germany) dealt with the monitoring of potential environmental effects of Bt maize on target and non-target organisms.  In reviewing the current status of Bt maize biosafety research, he discussed such aspects as insect resistance management (IRM, with most European experience in Spain), monitoring the susceptibility of the European Corn Borer (ECB), and also investigating non-target effects (NTE), where the challenge is in selecting adequate indicator species in agro-ecosystems.  Within Germany, ECB infestation decreases towards the north. Research sites in Germany currently total 9000 ha (IRM) and 50 ha (NTE).  

 

The components of IRM comprise such data as susceptibility of target pest (ECB and Mediterranean Corn Borer), gene flow within pest populations, allele frequency of Bt-resistance genes, development of management plans and the use of rapid diagnostic assays for detection of resistance. 

 

In terms of studying NTE, most work to date has been performed in the US and Canada, where the concern has primarily been the protection of Monarch butterflies. Bartsch outlined the desired attributes of a relevant indicator species for monitoring NTE, highlighting the relationship to nature conservation efforts, and discussing the key species for biodiversity preservation and also the relationship with economic value. The selection of a relevant monitoring species is decided according to a hierarchical scheme, beginning with the qualifying criterion of living on plants close to maize fields during pollen shed, and progressing through such factors as possession of chewing mouth parts and a mainly ectophytic habitat, ingestion of significant amounts of pollen, and whether the species is rare and/or endangered.

 

Daniel Amman (Bűro fűr Umweltchemie, Zurich, Switzerland) called for the urgent establishment of normative criteria (political and legislative) for the evaluation of GM monitoring results. In his view, long-term monitoring must meet organisational, scientific and political requirements. He opined that while organisational and scientific criteria have been relatively well discussed in the past, the political aspects of the issue have largely been ignored. The challenges facing this area include inadequate identification of environmental protection aims (such as protecting people, animals, plants, biodiversity and soil fertility), inadequate definition of leading guidelines and a lack of structures for applying the precautionary principle. 

 

Amman contended that one of the major hurdles is that there is no universally agreed notion of damage: insurers, lawyers and conservationists have a different assessment scale for this. The legislator must therefore be able to provide some practical answers:  for example, what out-cross rates from GM plants into wild and organic relatives are acceptable?  Can transgenic organisms that do not survive in areas cultivated by man be tolerated in conservation areas? 

 

However, Amman acknowledged that it will not be possible to define a general universally applicable notion of damage. Therefore, a method must be developed whereby a practical notion of damage can be laid down for particular circusmtances.  Amman suggested that scenarios are one possible way of assessing such situations.  In Switzerland a project has been started among 4 cantons to draw up relevant potential scenarios and to discuss them among experts in law, science and risk theory in order to establish thresholds. A total of 22 situations have been subdivided into ‘pathogen’ scenarios (M. tuberculosis – fire is a diagnostic lab), ‘GMO’ scenarios (recombinant rhizobia escape from a field trial), ‘exotic species’ scenarios (recombinant Trichoderma harzianum escapes from a lab and damages mushroom production) and ‘transport’ scenarios (transport accident at a postal centre).

 

Amman maintained that as long as environmental protection guidelines continue to be “vaguely worded” and open to ambiguous interpretation, the evaluation of the impact of GM plants will be problematical. By way of example, he pointed out that it is still unclear how environmental damage caused by a GMO should be defined, while key questions relate to the level of out-cross rates from genetically engineered plants into wild and organically-grown relatives which are acceptable. He recommended the proactive development of a number of possible scenarios, with key decision points interpolated against science, risk theory and national laws in order to establish damage thresholds.  A failure to accomplish this will mean that the notion of damage is likely to remain open to interpretations; additionally there will be no standards for the (consistent) decision of the authorities, the concept of ‘harmful’ or ‘inconvenient’ will be decided by court, insurers claims will be hindered and equality before law will be impeded. 

 

Conversely, the intrusion of politics into the scientific realm was strongly criticised by Anja Matzk (KWS Saat AG/Planta GmbH, Einbeck, Germany) as being an undermining factor in the safety assessment of GM crops.  Citing a need to avoid disproportionately onerous regulatory requirements (especially from the Small-Medium Enterprise – SME - perspective), she expressed concern regarding the political demand for zero thresholds of GM material in conventional seed.  Matzk articulated that for most companies, such demands carry technical and legal uncertainties, with unforeseeable and incalculable economic risks.  She projected that this would have long-term negative consequences for the European plant breeding industry and research, and also for imports.  For this reason, the adoption of feasible thresholds is urgently required. 

 

KWS has conducted field trials since 1993 and have gained their own experience with transgenic sugar beet (virus resistance, herbicide tolerance), oilseed rape (modified fatty acids, fungal resistance), potato (starch modification, reduction of amino nitrogen) and maize (herbicide tolerance, insect resistance). Matzk outlined that variety development is an arduous task for a breeding company, exacerbated by the need to produce an accompanying data package that must be science-based and include an Environmental Risk Assessment (ERA):  with respect to GM plants, this is based on both potential risk identification and the likelihood of hazard occurrence.  The safety of GM crops will depend on the characteristics of the inserted gene(s), the type of engineered traits and the intended use of the plant in a particular ‘receiving’ environment. Even after obtaining regulatory consent for market introduction, GM plants will continuously be monitored under EU Directives.  According to the new Directive 2001/18/EC (which is due to repeal 90/220/EEC in October 2002), the objective of a post-market monitoring plan is to confirm that any assumption regarding the occurrence and impact of potential adverse effects of the GM plant, or its use in the ERA, are correct, and also to identify the occurrence of adverse effects of the GMO or its use on human health or the environment which were not anticipated in the ERA. She highlighted that companies also support biosafety research in public and governmental institutions; by doing this they are in a permanent dilemma of being asked to support biosafety research, but are not trusted for the independence of the data which is generated.  She expressed that much of the work, such as removal of marker genes, “are not the result of sound safety concerns”, while the decision-making process is overly influenced by politics.   In closing, Matzk concluded that the results from biosafety research so far, and from the vast experience with large scale utilisation of GM plants elsewhere, is that their potential risks are not significantly different to those associated with traditionally bred crops. However, she admitted that the introgression of traits from crops into wild flora, the effect of large scale agricultural production on biodiversity, and the occurrence of volunteers in the rotation, are all general concerns. 

 

Andrew Cockburn (Monsanto Services International, Cambridge, UK) provided an industry perspective and case history of the existing industry approach to assuring the safety of GM crops.  He pointed out that crops and foods are “bulky”, and this attribute prevents the conventional approach used in toxicology based on administration of significant multiples of the likely human exposure in order to determine dose-response relationships. He described a rigorous holistic testing programme which attempts to systematically assure safety on a case-by-case basis.  As traditional foods and feeds are ‘generally regarded as safe’ (GRAS), the overall aim is to show that the novel GM crop, food or animal feed is as safe as its conventional counterpart (the doctrine of ‘substantial equivalence’). 

 

Cockburn defined the ‘audience’ for GM safety assurance issues as being farmers, processors, consumers, the general public, food producing animals and the environment.  The source of potential hazards were identified as the parent crop, the transformation process, the gene product and the GM crop (or elite event), and each of these is considered in the context of the type of risk, which can be toxicological (for example, allergy) or nutritional; possible horizontal gene transfer (to gut cells or bacteria) is also taken into account. The limitations of conventional chemical safety testing methodologies for crops-foods versus chemicals are numerous. The former represent a complex mixture of largely unknown molecules, with compositional variations arising from such factors as ripeness and growing location. There is also a pronounced difficulty in pinpointing toxicants. 

 

Cockburn described 3 phases of safety assessment for GM crops. Firstly, in phase 1 (‘research-discovery’), the safety of the gene, protein and crop are considered. In phase 2 (‘biological-agronomic equivalence’), a stringent evaluation of agronomic performance and efficacy is undertaken. In this step, more than 99% of all events are eliminated; this is also a key step in product evaluation for conventional varieties. In phase 3, a detailed product safety assessment is made: food, feed and environmental. 

 

Elaborating on the concept of substantial equivalence, Cockburn indicated that a central tenet was that differences between a GM crop and its conventional counterpart become a focus for further safety tests in comparison with the natural variation within the crop. Agronomic, genetic and compositional aspects are compared, focusing on known toxins, allergens and anti-nutrients. There is no single defining characteristic for a food allergen: an internal decision tree strategy is used which considers such issues as gene source, sequence homology with known allergens, immunological analysis and physicochemical properties (stability in pepsin and performance in animal models). The totality of assessments provides a reasonable assurance that foods will not be rendered newly allergenic.

 

A new GM crop is also subjected to tests for phenotypic stability, composition, nutritional equivalence and ‘wholesomeness’ (via feeding studies). A country-specific review of each GM crop is always conducted prior to commercialisation.  Key questions which are addressed include the potential for ‘weedyness’ of the crop plant, out-crossing/gene flow (where the existence of potentially compatible species is crucial), effects on non-target organisms, development of resistance and effects on biodiversity. 

 

Current status on world-wide legislation

Hans-Jőrg Buhk

The post-market monitoring obligations of the new Directive 2001/18/EC also formed a major focus of the event. Hans-Jőrg Buhk (Centre for Gene Technology, Robert Koch Institute, Berlin, Germany) felt that this new Directive will provide the basis for a stricter, more transparent regulatory framework. He recounted that European Community legislation on GMOs has existed in Europe since 23rd April 1990, being translated into national laws by the end of 1991.  Directive 90/219/EEC (which is amended by Directive 98/81/EC that will come into force in October 2002) covers only the contained use of genetically modified microorganisms (which includes in vitro culture of plant cells, and also viruses, and human/animal cell cultures).  Directive 90/220/EEC regulates the deliberate release of GMOs into the environment (for the purpose of field trials and also for placing on the market). 

Buhk made the point that the authorization of field trials is a national decision, but the placing on the market of a GM plant is a decision for the European Community as a whole: the final decision granted by the competent authority of the leading member state covers all member states. No new GMO products have received approval under Directive 90/220/EEC since October 1998. In order to restart the authorization process, the EC has invited member states to identify the practical means of ensuring adequate traceability, labelling and post-market monitoring. Buhk stressed the urgent necessity of clearly identifying a practical means to meet these requirements. Pending dossiers where no decision has been reached feature products such as transgenic chicory, rape, and fodder beet. 

 

Regulation (EC) No 258/97 on novel foods and food ingredients is a product-specific Community Directive. To date, only processed products which have been regarded as being substantially equivalent to conventional foods are on the market. There were 12 applications for a ‘GMO as a food’ pending under regulation (EC) No 258/97 up to September 2001.  One application had passed all stages of the safety assessment, but was withdrawn in September 2001 (a GM potato, where Zeneca was the applicant). Other applications include transgenic radicchio rosso with male sterility, green hearted chicory with male sterility, high oleic soybean sub-lines and Liberty Link^® soybeans.

 

 

Klaus-Dieter Schumacher (Alfred C. Toepfer International GmbH, Hamburg, Germany) provided the viewpoint of an agricultural goods trader on the issue of tracing GM material within the production chain. EU domestic use of protein feedstuffs in the 2001/02 period has been dominated by soybean meal (55%), followed by corn gluten feed (13%), rape meal (11%), sun meal (7%), palm kernel meal (5%) and others (8%).  However, since 95 - 97% of the soybean meal is derived from US, Argentina or Brazil, the EU livestock sector is now highly dependent on imported feed raw materials; the EU does not have sufficient capacity to plant a protein crop such as soybean. Of the 40 million tonnes of oilseeds and feedstuffs, nearly all contain a certain amount of GM components, meaning that Europe must now accept GM soybeans. 

 

The situation of Brazil as a source of non-GM soybeans was highlighted: difficulties in regulating the flow of seeds between borders means that an increasing percentage of the soybean harvest from this country is actually GM.

 

Schumacher articulated that identity preservation (IP) systems are only workable if there is a practical legal framework in existence, and if consumers are willing to cover the extra costs associated with this (which he doubted).  He criticised EC proposals on traceability of GM food and feed, on the basis that they were “out of touch” with the reality of detectability and enforceability. He opined that sampling and testing procedures were inadequate for the reality of ships carrying 100,000 tonnes of soybeans: with 1 ton of soybeans consisting of 7 million individual kernels, potential errors in taking a random sample abound.  Additionally, there are no validated standard testing and sampling methods. Indeed, tolerance to GM contamination would need to allow for both EU-approved and EU non-approved events.

 

On the issue of a niche market developing for non-GMO feedstuffs, Schumacher expressed doubts for the longer-term, as only a few consumers appear willing to pay the extra costs. Current demand for non-GMO soybean meal is about 1.5 million tonnes, which is approximately 5% of the total usage of 30 million tonnes.  He concluded that zero-tolerance is no longer possible, and advocated the use of a ‘non-GMO’ label rather than a ‘GMO-free’ designation.

 

Oliver Mellenthin

The costs associated with IP were further developed by Oliver Mellenthin (German Federation of Food Law and Food Science, Bonn, Germany).  While acknowledging a generalised request for non-GMO food products from EU consumers and retailers (“traceability is linked with IP as long as consumer acceptance is low”), he estimated a 5 – 15% increase in costs associated with practical IP approaches, and felt there was no big demand for this yet within the EU.

 

Mellenthin described two kinds of quality control regarding IP of GM crops.  ‘Hard IP’ comprises a system of contract guaranties and separated supply chains, with an example being the Wiesenhof feed for chickens (10 – 15% more costly, and no significant demand in EU yet), while ‘soft’ IP’ is based on accepting soybean meal from a ‘non-GM’ country or region, such as Brazil, and implementing testing procedures (about 5% more costly).  Additional costs will be incurred through audits at suppliers, increased personnel costs, recipe changes and adaptation of production documentation. Therefore, the requested traceability systems will result in additional costs for producers. 

 

The traceability of GM material in the seed production chain was provided from the German plant breeder’s perspective by Dietmar Brauer (Norddeutsche Pflanzenzucht Han-Georg Lembke KG, Malchow/Poel, Germany).  The German seed industry comprises such actors as plant breeding companies, multipliers and seed marketing organisations that have all been established for decades.  The German Federal Variety Certification Office (Bundessortenamt) is responsible for ensuring homogeneity of the new variety, testing it for 2 – 3 years during which the stability of the characteristics is monitored. The new variety must be deemed novel, homogenous and superior to previously listed varieties, at which point the Federal Certification Office registers it on the German variety list.

 

The standards used in Germany are based on the Seed Regulations and Rules of the EC Seed Directives.  OECD and ISTA rules are binding for international trade, so that seed lots need OECD certificates from these organisations.  Therefore, no seed leaves the breeding company without having been tested first for the presence of GMOs. However, errors in such areas as taking a random sample and in analytical methods cannot be completely excluded. Increasingly, Brauer finds that recipients of seeds are asking for a declaration of conventional breeding. 

 

Describing the seed production path from the nursery to the farmer, Brauer began by highlighting that rapeseed breeding programmes are separated on the basis of the plant’s fertilization system and also environmental conditions.  Typical quality traits currently being developed include either ‘zero’ or ‘high’ erucic acid and ‘low’ glucosinilate.  All of the GM variety breeding programmes are classified as ‘security step I’.  Typical containment of such varieties entails growth in isolated greenhouse compartments, while later field trials are performed in isolated parts of a field.  Pollen flow is controlled via changing workers’ clothes, and any tools used are cleaned thoroughly with alcohol. Additionally, the trial field areas will not be used for the production of rapeseed in the following years, while any off-types growing in subsequent seasons will be removed before flowering. 

 

Seed production and multiplication is regulated by Certification Rules laid down by European Commission law. There are already existing fixed minimum isolation distances between different varieties of the same crop, and the previous cropping of the production field must also be correct. This process aims to protect the farmer from the mixing of seed varieties, and therefore from seeds of low quality.  However, within this system, tolerances and thresholds are necessary.  Such procedures are inspected as prescribed by the law for Trade in Seeds and the Seed Certification Directives.  For some crops, it is usual to produce the seeds in third countries and to import them into the EU.  For example, seeds may be produced in the southern hemisphere during winter and imported into Germany in the spring (accompanied by OECD and ISTA certificates as part of the transportation papers).

 

The essential quality parameters in seed production are germination, minimum purity, contamination, trueness of variety and thousand-grain weight. Through stringent monitoring processes, the path to a new variety is retraceable from the producer (multiplier) back to the initial cross made 10 – 12 years before.

 

Seed testing is based on a representative seed sample, regulated in Germany by the Working Group of the Official Certifying Institutes.  However, on the issue of GMO analyses, responsibilities are not yet clearly defined in Germany, and Brauer contended that samples are sometimes currently being taken by non-qualified persons (for example, by the Ministry of the Environment). While seeds are analysed in accredited laboratories (mainly agricultural research institutes in the Federal states), these institutes are usually not equipped with PCR facilities or are not able to carry out large numbers of GMO analyses in a short time (within the few weeks between harvest and sowing). Only private companies appear to have the necessary qualitative and quantitative capacities. Brauer called for all persons to agree on these accredited laboratories, or else suggested that the government should set up the respective institutes with the right equipment and personnel. He also called for the methodology to be fixed in law. Significantly, the perceived unfavourable political response to this issue from European legislators has prompted Brauer to transfer GMO fieldwork research to the US, thereby damaging Europe’s capacity as a research location.

Brauer pointed out that in addition to rapeseed, maize is also among those European crops which have been genetically modified and are commercially grown in the US, while he also stressed that the analysis and traceability of GMO DNA is much more complicated for crops such as cereals, sugar beet and potato varieties, due to the larger volumes and the greater number of partners involved in their production chain. 

 

Against the current debate surrounding the possible adventitious presence of GMOs in the seeds of conventionally bred varieties, a basic paper by the Bundesverband Deutscher Pflanzenzüchter (Association of German Plant Breeders), entitled ‘Transparency and Quality Safety from the Breeder to the Farmer’, was prepared by rapeseed breeders.  This was aimed at ensuring the production of high quality rapeseed, without GMO contamination, by means of common agreed standards.  As there are no basic regulations set by the German authorities with regard to GM contamination, the breeders created their own rules.  However, they did not envisage that politicians would demand zero as a threshold in the field, or that this would become the legal standard.  Brauer opined that since genetic engineering as a breeding technique has been used for more than 10 years, a return to the original level of zero is impossible: “pollen spreads – also pollen of GMO plants”. 

 

Brauer finished by saying that at present GMO contamination can never be totally avoided even by the correct application of the Law for the Trade in Seeds and the Seed Treatment Rules, as well as the quality control systems of the seed companies.  He articulated that GM contamination of seeds was unavoidable due to such factors as pollen transfer (via wind, insects, tools, and clothes), mixing of seeds in the technical processes of harvesting, transport, drying and cleaning, packing and storage, and also uncontrolled production of non-certified seeds.  

Anja Krech

 

Anja Krech (GeneScan Europe AG) delivered a presentation on the technical innovations for GM analysis, with proprietary systems showing highly sensitive quantitation limits of 0.1% GMO content.  The two most common methods used in the European arena are ELISA and PCR.  ELISA involves the detection of specific proteins via antibodies and represents a quick and easy method for detection of GMO-specific proteins.  It can be used for detection of GMOs in highly processed products, such as boiled soybean or soymeal. Krech also discussed the use of multiplex PCR in the context of the need for specific detection of about 20 different approved GM-corn varieties in order to fulfil labelling requirements.

 

 

Charles Kessler (Research Directorate-General, European Commission) provided an update on the status of the EU Round Table on GMO Safety Research. In recognition of the polarity in the GMO debate in Europe, on the 9th October 2001, Commissioner Busquin launched an EC Round Table on GMO safety research (part of a wider debate entitled ‘Life sciences and biotechnology – a strategy for Europe’). The latter aims to achieve a balanced discussion among all stakeholders on the results of GMO research ((http://biosafety.cordis.lu/).  It especially strives to avoid a ‘for’ or ‘against’ argument, but rather focuses on examining the facts and the areas of uncertainty. To achieve this objective, topics are focused on a single area, which for the first meeting was an analysis of the benefits and risks of Bt maize (taking into account environmental, animal feed and human food issues). During this meeting, no previously unknown risks associated with the use of Bt maize were revealed, but a range of topics deserving of further research were identified. These included base-line studies and manipulative field experiments to determine benefits and/or risks of new components (GM and conventional), the establishment of practical measures to permit coexistence of different production systems, further studies on Bt toxin impact and persistence in the soil, and the establishment of resistance management/prevention strategies.  The topic of the second round table held in April 2002 was herbicide tolerance in crops.

 

Kessler described that over the last 15 years, some 80 projects involving over 400 research teams and an EU financial contribution of over €70 million have been supported in the area of GMO safety. The EC considers GMOs to be neither inherently risky nor inherently safe. Research has covered investigations of plants, biocontrol agents, food, fish, vaccines and bioremediation.  During the course of this work, no particular safety or environmental problems have been revealed.  However, analysis of GM in agriculture has raised questions on conventional agriculture (http://europa.eu.int/ comm/research/quality-of-life/gmo/index.html). The current Fifth Framework Programme features research on topics such as the ecological effects of virus-resistant transgenic plants, non-target effects of Bt transgenes, gene flow from transgenic plants and various aspects of food safety.  More recently identified research priorities include baseline studies to define agro-ecosystems, large scale manipulative field experiments to determine benefits/risks of new components, separation distances for coexistence/validation, impact/persistence of recombinant products in soil, and gene stacking. 

Peter Kearns

 

Peter Kearns (Organisation for Economic Co-operation and Development) reviewed the benefits of international cooperation amongst regulatory agencies on GM issues.  He discussed the Task Force for the Safety of Novel Foods and Feeds, which comprises personnel mainly from ministries or agencies involved in safety assessment (the competent authorities of national states).  He also reviewed the activities of the Working Group for the Harmonisation of Regulatory Oversight in Biotechnology.  BioTrack Online (http://www.oecd.org/ehs/ service.htm) details the regulatory developments in OECD countries, providing a database of field trials of GMOs and a database of commercialised products, and also outlining the OECD’s work in this area.

 

 

 

Manfred Kern (Aventis CropScience) delivered a presentation entitled ‘green biotechnology:  perspectives for developing countries between 2002 and 2025’.  Based around such key questions as ‘how can we feed the future world population in a sustainable way and in keeping with human dignity’, he focused on reconciling future food needs with a rapidly expanding world population.  In 1850 the number of people on Earth was approximately 1 billion, and during 1999 the number reached 6 billion.  Mean estimates indicate that by 2025 the world population will have risen to 8 billion.

 

Kern contended that biotechnology will play a deciding role in preserving global self-sufficiency and the environment.  In order of magnitude, he predicted that the impact of biotechnology will be felt primarily in developed countries, followed by Asia, Latin America and Africa.  He also projected that by 2025, the developed world (US, Europe, Canada, Australia) will produce 28% of its food using GMOs, followed by Asia (20%), Latin America (17%) and Africa (6%). 

 

Currently, only about 0.26% more food is being produced than is actually consumed.  Over the next 30 – 50 years, world food requirements will more than double, and this will make it necessary to double and even treble agricultural production and supplies. At the same time, it will be necessary to compensate for the loss of arable land, water shortages and the switch from plant-based to meat-based diets.  While in 2000, agricultural trade represented only about 10% of global production, in 2025 it will constitute about 30%. The future challenges will include food security, hunger, poverty and livelihood security, environment, new trade regimes and social and ethical issues.  Global food security will depend on a fine balance of availability versus accessibility. Kern pointed out that the ‘poor have-nots’ are poor in resources and possess complex farming systems, with fragile soils and a highly variable climate. Low rainfall and limited irrigation potential limit agriculture and ensure that productivity is low. In contrast, the biotech agenda is based on increasing the availability of food, feed and raw materials, improving human health and enhancing protection of the environment. Kern contended that lack of access to biotechnology will result in developing nations missing out on a powerful opportunity, and that this represented a form of apartheid

 

The global variety of GM plant research spans input traits (cold/frost  tolerance, delayed ripening), ornamental-flower crops (longer-lasting cut flowers, modification of colours), medicines and industrial products (production of human vaccines in plants, new carbohydrate polymers, biofuels) and output traits aimed at consumers (enhancement of nutritional value, lower levels of toxic components, such as cyanogenic glucosides in cassava, and higher proportion of antioxidants). 

 

Kern reported that China is developing the largest plant biotechnology capacity outside of North America, with a greater percentage of small farmers cultivating more area of GM plants than any other developing country.  China’s government funds almost all of its plant biotechnology research: the total investment in 1999 was about $112 million, and it reportedly intends to raise budgets by 400% before 2005.  The area sown with Bt cotton grew to around 700,000 hectares in 2000.  Simultaneously, the use of plant protection products in cotton was reduced by more than 80%.  In finishing, Kern posed the question of whether the private sector could be persuaded to become an active partner in agricultural research.  He envisaged that a number of conditions would need to be fulfilled before this happened, including the establishment of a formal system of authorisation to ensure worldwide deregulation standards are met, assurance of enforceable protection of intellectual property, and development of infrastructures for national and international technology transfer, including analytical processes for GM monitoring. 

 

José Falck-Zepeda (ISNAR International Service for National Research, The Hague, Netherlands) provided a research perspective on biosafety assessment and crop biotechnology in developing countries, outlining the public sector agbiotech pipeline and considering the regulatory and capacity-building implications for biosafety assessments. An ISNAR database of outputs produced by the public sector (‘The Next Harvest©’) comprises regulatory categories such as laboratory, confined field, scale-up and commercial use. It is hoped that this database will help increase the understanding of research, transgenic events and regulations.

 

José Falck-Zepeda

Falck-Zepeda indicated that while the public sector pipeline is increasing and diversifying, as yet there are few available alternatives to the private sector. Food crop research objectives are only slowly being concentrated on local biotic stresses. He contended that regulatory, environmental and political hurdles and moratoriums all limit advances, and constrain capacity and funding in this area.  Reviewing the biosafety regulatory policy and procedures of Egypt and Argentina, he noted that these countries have similar strengths:  they both have guidelines in place, their people are confident (within limits) and competent in their decision making, reviews are science-based and timely (within limits) and continuous feedback is being used to improve the system.  In both countries, the biosafety review process is guided by an advisory committee, requiring approval by the Minister of Agriculture, and is performed by unpaid ‘volunteers’ from advanced research institutes and organisations. These assessments tend to focus on risk with very little or no benefit analysis. In both countries, the different stages of the review process are implemented as needed, not as a system with previously defined objectives.  The analysis of these systems shows the need to revise national biosafety guidelines, to strengthen institutional roles, and to enhance transparency and efficiency. This is turn will improve biosafety procedures and decisions that should help build public awareness and confidence in the system.  From the standpoint of public policy, it then becomes important to define risk and benefit criteria that set trade-off levels between productivity (income) and environmental/health effects.

 

Future initiatives

Klaus Minol (Genius GmbH, Germany) delivered a talk entitled ‘dialogue and transparency:  an innovation approach for communication on biosafety research’, with a key message that the success of innovative technologies will depend on the

agreement of customers, distributors and users.  He outlined that a new BMBF-funded project has been launched, entitled ‘communication management’, and this is composed of two complementary strands, ‘dialogue’ and ‘transparency’.  The work attempts to develop an innovative multidimensional communication concept, with many phased approaches. The character of the concept includes such elements as transparency and candour on the issue of research results (as well as on the whole biosafety research process), increased availability of natural science insights, building trust and credibility through transparency and personal contacts, and the establishment of communication and information networks. It emphasizes improvement of perception, establishment of a neutral information and dialogue platform and the creation of networking and feedback platforms for science, society and politics.

 

Management of the ‘dialogue’ component is being carried out by the University of Bielefeld and IFOK, while the information points on biosafety research are Genius Gmbh, Transgen and TUV Nord (www.biosicherheit.de).

 

Minol contended it was inevitable that public opinion be taken into account regarding the development of GM technology. He further opined that there was still a lack of public perception about biosafety research, despite the efforts of the BMBF. Communication management on biosafety research, in conjunction with appropriate research projects, provides an improved information exchange platform with the public, and also a better dialogue between society and the economy for linking the various actors. Minol stressed that communication management does not aim at creating acceptance of “green genetic engineering” per se, as it cannot replace the public discussion process. 

 

Jens Katzek

Jens Katzek (German Association of Biotechnology Industries, Frankfurt, Germany) reviewed the German political situation as it affects biotechnology safety research.  He highlighted the contradictory positive and negative signals on this issue that have emanated from the German government. For example, in support of green biotechnology, the BMBF is funding plant genome research, with €12.5 million allocated in 2001 and €15 million in subsequent years. The BMBF also supports the Bioregion Potsdam and their ‘Food Related Diseases’ programme to the tune of about €15 million, and about €170 million is invested in a genome research network.  However, he highlighted that no authorisation for a GM seed variety has been forthcoming by the Bundessortenamt due to “political interference” from Minister Renate Kunast (of the Green Party German government partner). He further opined that there have been unrealistic requests concerning adventitious presence of GMOs in food or seeds, accompanied by a growing bureaucratic burden, and also political support for the moratorium within Germany. 

 

Katzek criticised the Kunast debate on plant biotechnology, opining that it focuses on purely hypothetical risks, while it is also attempting to target too many diverse topics (spanning sociological, economic, social and health risks, consumer choice, alternative agricultural concepts and Third World aspects).  He felt that this initiative lacked an appreciation of how national agricultural production and food consumption issues are closely connected to international trade. 

 

Katzek proposed that the elements of any national biotechnology strategy should offer legal certainty, realistic goals when drafting new rules, consistent policy and also prevent product discrimination. 

 

Val Giddings (Biotechnology Industry Organization, USA) delivered a presentation entitled ‘public opinion about biosafety in the USA’.  US Public support varies according to different applications of biotechnology, with the production of new human medicines carrying the highest approval rating (85%), and increased animal productivity carrying the lowest (35%). Interestingly, support for crops to produce plastic was also high (at 74%). US citizens tend to show a broad acceptance of biotechnology, with human genetic screening, production of new human medicines, insect-protected crops and improved foods all showing in excess of 58% support.

 

Between 1995 and 2001, the American consumers’ willingness to buy GM produce appears to have been fairly consistent, but at the same time their awareness of biotechnology has been low, influenced intermittently by the media.  When compared on an inter-country basis, consumer agreement with the statement that the ‘benefits of using biotechnology are greater than the risks’ gained highest acceptance for the US (66%), followed by Asia (60%), Latin America (59%) and Canada (55%).  Unsurprisingly, Europe was lowest at 38%.  Curiously, 62% of US citizens state emphatically when asked that they have not eaten GM produce, compared to 19% who feel they have consumed it.  Research from the Pew Initiative has shown that perceptions about food safety tend to improve (from 29% to 48%) when people learn that biotech foods are in the stores. Regarding labelling, results from a synthesis of focus groups suggests that people are already overwhelmed by information and choice. While many claim to want information about all aspects (even harvesting), the most important information involves nutritional data. There appears to be less desire for labels on processed foods (or meat) compared to whole produce items. There is also an unwillingness to pay for labels, while voluntary labelling of ‘non-GM’ foods facilitates choice for concerned consumers. When consumers are asked ‘can you think of any information not currently included on food labels that you would like to see’, various studies have shown responses spanning ‘nothing’ (>70%), ‘ingredients’ (7-12%), ‘biotech/GM’ (1-2%) and ‘other’ (7-11%).  About 44% of US consumers are unwilling to pay any more per year for GM labelling, followed by those willing to pay $10 (17%), $50 (16%), $250 (5%) and >$250 a year (7%).  US consumers’ primary concerns have been found to be bacterial contamination, followed by pesticides and biotechnology-GM.

 

Giddings closed his presentation by saying that the outlook for North America is positive for GM foods, despite “visible issues”.  Ongoing education efforts have been effective with opinion leaders and consumers. Media coverage of GM issues should grow, but is likely to be balanced, while Giddings felt that protest groups currently have low credibility.  Plant biotechnology should not become an issue for most consumers, unless impacted by other issues.  The criteria for consumers’ food selection should remain value, taste, nutrition and convenience (and not seed genetics).

 

Words and photographs copyright Gwilym Williams, BioResearch Ireland, 2002.  The author’s own views are represented in this article. A summarized version of this report is available:  Williams, G.A. (2002). Safety aspects agricultural biotechnology: consensus still a distant prospect in the EU.  BIOforum International 6(3), p. 138.