Whether GM foods are safe is a controversial question; the answer is presently unclear, although new information is being accumulated rapidly.
Substantial equivalence
The principle of substantial equivalence is used to compare a GM food to its non-GM counterpart. If substantial equality is established, the GM food is considered safe. However, how to assess substantial equivalence remains a fundamental problem with this approach.
For crops, for example, comparisons may be made between phenotype or compositional characteristics, or toxin production. One problem of assessing equality in plants is due to the large sample sizes required. Small changes may remain hidden except in the face of extensive sampling. For the same reason, crop sampling must be conducted in varying locations and seasons. It could be presumed, in general, that more profoundly modified crops probably present greater risks from unintended modification effects than do less modified crops.
For animals, establishing equality between GM- and non-GM organisms is also a guiding principle in establishing GM safety. If the inserted DNA is well characterized, it can be extracted from the host animal post- modification, and compared with the original insert. The gene products of inserted DNA can be studied (up-regulation or down-regulation of the inserted gene), as can other differences between GM and non-GM animals.
One aspect of genetic modification in animals that needs attention is the technique of modification for disease resistance. Although such animals should not develop disease, they may represent a risk to human health by carrying the disease or disease agent asymptomatically. In such a case, overall, they may produce greater risks of human infection via the meat chain. Also, compositional analysis could be applied in equality studies, although novel methods may be required, as should the consequences of
under- or over-expression of genes. There are few peer-reviewed data on the equivalence of GM and non-GM foods. Only one human feeding trial has been published, in which fish (tilapia) modified with growth hormone were fed to humans and, simultaneously, monkeys were injected intravenously with the produced growth hormone. No adverse effects were observed in this human feeding trail. In a second trial, fish (carp) modified with growth hormone were fed to mice. No adverse effects were found.
Nonetheless, these trials were relatively limited in focus, and do not provide any wider conclusion about the safety of GM foods.
Animal welfare is another issue to be addressed when considering the safety of GM; there should be equivalence in all aspects of animal welfare between GM- and non-GM animals.
Allergens
Allergic reactions can be life-threatening, and GM technology could increase the risk that individuals are exposed to allergens without their knowledge. A FAO/WHO decision tree is used to assess the allergenicity of GM foods. First, sequence comparison of the expressed protein with very well-characterized, sequenced allergens is conducted (e.g. strawberry or groundnut proteins, known to be frequently allergenic). Second, if the gene source is a known allergen, its reaction with sera from allergic patients is examined. This is followed by further testing with sera from patients allergic to organisms broadly related to the gene source. Third, the effects of in vitro digestion with the stomach protease pepsin are studied. Finally, in vivo animal testing is required to complete the examination of allergenicity in a GM food. Some animal products contain substantial amounts of allergens (e.g. cows’ milk, the shrimp protein tropomyosin); there are concerns whether these would be increased by gene modification of the animal itself. In contrast, experimental GM crops with reduced concentrations of intrinsic allergens have been created.
Gene transfer
The issue of gene transfer as a result of genetic modification of foods requires attention. Antibiotic resistance genes were often used in the production of some GM micro-organisms. Chosen antibiotic resistance genes, combined with the gene of interest, are inserted into a bacterial plasmid (highly mobile genetic elements, which can transmit easily from one bacterium to another). The GM plasmid is inserted into bacterial cells which are cultured on media containing the antibiotics. The GM plasmid itself can then be purified and used for plant modification. There is a risk that antibiotic resistance genes and the gene of interest could be transferred to other bacteria after consumption of the GM crop. Within the EU, the only gene initially approved for this procedure was for
kanamycin resistance. Recently, however, the practice has been banned altogether within the EU, where the problem of antibiotic resistance gene transfer is perceived to be a very serious issue.
During genetic modification of animals, antibiotic resistance genes are not frequently used, although there is the potential for some problems to occur even without their use. First, wild plasmids can naturally harbour antibiotic resistance genes, and if such plasmids are used to prepare GM animals, the resistance genes could transfer unintentionally. GM animals could shed resistance genes in epithelial cells from the gastrointestinal tract mucosa and, subsequently, the genes may be transferred to bacteria in the GI tract. Also, inserted retroviral sequences in animals (GM poultry) could combine with wild-type viruses, potentially creating new retroviruses.
Retroviruses are a common vector for genetic modification of animals, and attempts are being made to produce artificial retroviruses not prone to recombination.
Pre-market and post-market assessments
Safety assessment of any food should be conducted before it is released onto the market. However, in the case of GM foods, the question arises of what safety assessment to conduct if the food is already on the market.
Recent EU legislation requires that cultivated GM foods undergo monitoring and surveillance for substantial periods for unanticipated, undesirable long-term effects. In effect, this requires a programme for long-term surveillance and monitoring, including the time following the product’s arrival on the market. Surveillance of plants or crops during normal trade and business is perhaps the hardest thing to achieve, as substantial mixing of ingredients, companies, places of origin etc. can occur. Due to their lack of traceability, GM crops could easily be ‘lost’, rendering surveillance or monitoring programmes defunct.
Animal traceability is already undertaken at a much higher level than with plants, so tracking GM animals for monitoring and surveillance should be less complex. However, legal definitions of GM animals as
‘veterinary medicines’ can confound the problem. Some producers have made the case that animals containing transgenic growth hormone should not be subjected to food legislation but, as a source of the growth hormone itself, should be subject to less stringent veterinary medicine legislation.
Veterinarians must be aware, from a public health point of view, of such attempts to confound the intent of the law.
Regulatory aspects
The cultivation, trade and food and feed industry is subject to national regulations, with the safety assessments as part of the admission procedure. National regulations for cultivating GM crops can differ
between countries, although GM crops are widely marketed. In the EU, legislation is generally more stringent compared with the USA, and a trade war has developed partially as a result of these differences.
International harmonization initiatives are under way. Guidance documents by the Organisation for Economic Cooperation and Development (OECD) have been completed for soybean and oilseed rape;
guidance documents for potato, sugarbeet, wheat, maize, rice, sunflower and cotton are under way. OECD guidance documents aimed at harmonization have been produced, including GM feed production for farm animals and GM feed production for pets. The Codex Alimentarius Intergovernmental Task Force on Foods Derived from Biotechnology is organizing expert consultations, and related risk analysis documents are being drafted; these will probably be adopted in a few years.
However, the production and use of GM animals has limited regulatory coverage. To date, two applications for GM animals to be marketed to consumers are known. In Australia, Bresatec pigs were found to contain transgenic growth hormone, designed to be ‘switched on’ when the livestock were fed zinc. The company abandoned the project when the relevant food safety authority declared itself not responsible for GM animals, and the supermarkets stated their reluctance. AquAdvantage salmon (USA) is transgenic for a growth hormone gene under the control of a promoter from the ocean eelpout’s antifreeze protein gene. The application for this new animal drug, intended to be marketed as a human food, is pending and should involve numerous risk analyses including environmental risks (wastes, pens) and food safety risks.
In summary, existing data on the use of GM foods indicate:
1. Knowledge about the use and consequences of GM foods is limited.
2. Lack of evidence must not be interpreted to mean a GM food is safe.
3. Clear guidance on the suitability of assessing GM foods under existing food or drug legislation is required.
4. Methods for assessment of the safety of GM foods must be improved.
5. Proper labelling is essential, to provide consumers with choice, and to enable producers to emphasize improved product quality. Currently, labelling is not mandatory, and may be opposed by regulatory agencies on the basis of cost, stigmatization of products and logistical difficulties.
Further Reading
Anon. (2001) EU Directive 2001/18/EC on deliberate release into the environment of geneti- cally modified organisms. Official Journal of the European CommissionL106, 1–39.
Anon. (2004) Guidance document of the scientific panel on genetically modified organisms for the risk assessment of genetically modified plants and derived food and feed. EFSA Journal90, 1–94.
Kleter, G.A. and Kuiper, H.A. (2002) Considerations for the assessment of the safety of genetically modified animals used for human food or animal feed. Livestock Production Science74, 275–285.
OECD (1993) Safety evaluation of foods derived by modern biotechnology: concepts and principles.
Organisation for Economic Cooperation and Development, Paris.
Schilter, B. and Constable, A. (2002) Regulatory control of genetically modified (GM) foods:
likely developments. Toxicology Letters127, 241–349.
WHO (1987) Principles for the safety assessment of food additives and contaminants in food. WHO Environmental Health Criteria No. 70, IPCS-Program, World Health Organization, Geneva.