Electronic Journal of Biotechnology ISSN: 0717-3458 Vol.9 No.4, Issue of July 15, 2006 © 2006 by Pontificia Universidad Católica de Valparaíso -- Chile DOI: 10.2225/vol9-issue4-fulltext-12 REVIEW ARTICLE Safe use of genetically modified lactic acid bacteria in food. Bridging the gap between consumers, green groups, and industry Wilbert Sybesma Wageningen Centre for Food Sciences Diedenweg 20, 6703 GW Wageningen The Netherlands Tel: 31 317 485 383 Fax: 31 317 485 384 E-mail: [email protected] Jeroen Hugenholtz NIZO Food Research Kernhemseweg 2 PO Box 20, 6710 BA, Ede The Netherlands Tel: 31 318 659511 Fax: 31 318 650400 E-mail: [email protected] Willem M. de Vos Wageningen University Department of Microbiology Hesselink van Suchtelenweg 4, 6703 CT Wageningen The Netherlands Tel: 31 317 482105 Fax: 31 317 483829 E-mail: [email protected] Eddy J. Smid* NIZO Food Research Kernhemseweg 2, PO Box 20, 6710 BA, Ede The Netherlands Tel: 31 318 659511 Fax: 31 318 650400 E-mail: [email protected] Financial support: Commission of the European Union through contract QLK1-CT-2000-01376 “Nutra Cells”. Keywords: lactic acid bacteria, genetic modification, legislation, novel foods, safety assessment. Abbreviations: DRI: daily recommended intake EFFCA: European Food and Feed Culture Association GRAS: Generally Recognized As Safe LAB: lactic acid bacteria NICE: nisin induced controlled expression system PMS: post-market surveillance QPS: Qualified Presumption of Safety Within the European Union (EU), the use of genetically assessment of genetically modified microorganisms. modified organisms (GMOs) in food production is not Since these procedures are not yet implemented, the widely applied and accepted. In contrast to the United current risk assessment procedure is shared for GMOs States of America, the current EU legislation limits the derived from micro organisms, plants, or animals. At introduction of functional foods derived from GMOs present, the use of organisms in food production that that may bring a clear benefit to the consumer. have uncontrolled genetic alterations made through Genetically modified lactic acid bacteria (GM-LAB) can random mutagenesis, is permitted, while similar be considered as a different class of GMOs, and the applications with organisms that have controlled genetic European Union is preparing regulations for the risk alterations are not allowed. The current paper reviews *Corresponding author This paper is available on line at http://www.ejbiotechnology.info/content/vol9/issue4/full/12/ Sybesma, W. et al. the opportunities that genetically modified lactic acid Consequently, organisms in which the genetic material has bacteria may offer the food industry and the consumer. been altered by recombinant DNA techniques in a way that An objective risk profile is described for the use of GM- does occur naturally, for instance by point mutations or LAB in food production. To enhance the introduction of small deletions, are considered to be GMOs. Secondly, functional foods with proven health claims it is foods with a new structure which date from before 1997 are proposed to adapt the current safety assessment not considered as novel foods. Thirdly, self cloning (Box 2) procedures for (GM)-LAB and suggestions are made for of non-pathogenic micro-organisms is not considered to the related cost accountability. A qualified presumption lead to a GMO as long as containment of the organism is of safety as proposed by SANCO (EU SANCO 2003), guaranteed (directive 90/219/EC). However, the same self- based on taxonomy and on the history of safe use of cloned micro-organism when used in products (deliberate LAB applied in food, could in the near future be applied release) is considered to be a GMO (directive 2001/18/EC). to any kind of LAB or GM-LAB provided that a series Moreover, the market introduction of foods with organisms of modern profiling methods are used to verify the that have been improved via classical breeding or random absence of unintended effects of altered LAB that may mutagenesis is currently acceptable without profound safety cause harm to the health of the consumer. analysis[1], but it could be questioned whether these foods are more safe than GMO-derived novel foods. The new Ever since human domestication took place approximately regulation 1829/2003 (amending 258/97) regulates the 10,000 years ago, parts of our food supply have been approval and the labelling, and distinguishes between cultured in order to support survival of the human products from GMO, and products which are produced with population. In our current times, the main objectives of help of GMO. Foods, ingredients, additives, flavours as agriculture are still the same, the assurance of efficient food well as feedstuffs, which contained or are GMO, or which supply in the first place, and the increase of quality of the were produced from GMO are in the scope of the supplied foods for the consumer in the second place. regulations. The labelling of these products is also process- Modern biotechnology, using recombinant DNA oriented. Products produced with help of GMO are not in technology, offers ample opportunities to further improve the scope of the regulations. It is still unclear if the food production in the expanding world of today. regulations can be applied on the use of GMO (micro- organisms) within fermentation (Jany and Schuh, 2005). Within the United States of America there is not much public resistance towards the use of genetically modified The rationale for food safety regulations is the assurance to organisms, GMOs (Box 1), in food. However, in other prevent any adverse effects on human health or on the areas of the world, for instance Oceania and Europe, the environment. The starting point for a food safety approach production of novel foods using GMOs is subject to strong is the comparison between the new foods and the debate. For example, within the European Union the conventional counterparts that have a history of safe use, scientific community states that there is sufficient both for the food produced and for the micro-organism that legislation to guarantee that such novel foods are safe for is modified. This approach leads to identification of new or the consumer and the environment, but green groups in altered hazards relative to the conventional counterpart many cases state an opposite opinion. The support for the (substantial equivalence, Box 3) is essential (OECD, 1993). use of GM crops and foods among the European population has recently increased in some countries. Yet at the same This document will analyse the current situation within time a majority of Europeans do not support agri-food Europe with regard to the safe use of novel foods derived biotechnology (Gaskell et al. 2003). In the current debate from genetically modified lactic acid bacteria (GM-LAB). about the application and safety of GMOs in the food The application and safety assessment of genetically industry no clear distinction is made between GMOs modified yeast and fungi are not discussed; neither is the derived from animal, plant, or microbial origin. Moreover, use of GMOs derived from plants (Kuiper et al. 2001) or ethical aspects could play a role in the debate about GMOs animals. Genetically modified microbial inoculants for use from animal or plant origins, but these are considered less in agriculture, such as biological control agents, relevant in the discussion about genetically modified micro- biofertilisers, or phytostimulators is reviewed elsewhere organisms. Apart from this, the current European (Amarge, 2002; Morrissey et al. 2002). An overview will legislation on novel foods and the use of GMOs in food be given of the specific genetic techniques that generate production processes, as laid down in the regulation EC No GM-LAB and the advantages that the novel foods 258/97, amended in regulation 1829/2003, directive fermented with GM-LAB may bring to the consumer or the 2001/18/EC (revised directive 90/220/EC), directive producer. Moreover, the current safety assessment 90/219/EC, and Commission Recommendation 97/618/EC, procedures are considered and further suggestions are made generates a framework for what should and what should not for an adequate risk analysis when GM-LAB are applied in be permitted by law. The legislation, however, is not yet food production. Careful analysis of the properties of GM- completely clear on a number of important scientific LAB combined with a profound safety assessment matters. First of all, the legislation predominantly focuses procedure for foods that are produced through the actions on the methodology rather than on the end product and of GM-LAB, are essential for comparing the safety of such hence, holds too strongly to the definition of GMOs. products with traditional foods. Finally, based upon the 425 Safe use of GM-LAB in food Table 1. Types of DNA modification methods and the acceptability to be used in food production. Acceptance of Acceptance of Directed genetic Un-controlled Modification of DNA contained use, deliberate release, alteration genetic alteration 90/219/EC 2001/18/EC Spontaneous mutations - + + non-GMO + non-GMO Induced mutations - + + non-GMO + non-GMO Mutations via insertion - + + non-GMO + non-GMO elements Conjugation + - + non-GMO + non-GMO Transduction + - + non-GMO + non-GMO Self-cloning + - + non-GMO - GMO Non-self-cloning + - - GMO - GMO principle of assuring food safety for the consumer, it could and medicine and many health claims assigned to probiotics be argued to make no distinction between foods produced are not yet scientifically proven. Another application - the by LAB that have been altered in an uncontrolled way, for use of LAB in the production of proteins for application in instance by random mutagenesis, or a more directed way, health care or for development of new vaccines (Mercenier such as GM-LAB. This could imply that all foods et al.