Impact on human health

The potential for transferring genes from one unrelated species to another has caused concern that allergenicity may be introduced into a food source that was previously non-allergenic. An obvious example is that of the recent research programme by Pioneer Seeds where soya bean transformed with a gene from the Brazil nut was found to have allergenic properties. The research programme was halted before any field trials took place but public concern was heightened by reports of this work. All GM foods are now routinely tested for allergenicity using serological tests involving immuno-globulin antigens for specific allergenic proteins.

Transgene instability may be an important issue in the case of transgenic plants engineered to remove the synthesis of harmful toxins. In this situation suppression of gene expression arising from gene flow leading to multiple transgene insertions could prove a serious human or animal health problem if undetected.

The inappropriate choice of transgenes for achieving a desired trait may also have a serious impact on human health without adequate risk assessment. Lectins are a group of proteins known to have insecticidal properties that make them attractive candidates for the development of transgenic plants with resistance to the Homoptera insects. They are thought to work by binding carbohydrate side chains present in the gut wall resulting in inhibition of food absorption. As there is the potential of toxicity to humans, it is essential that extensive risk evaluation is required to establish any potential threats of toxicity. The need for such risk assessment is reflected in work on GM tomatoes (Noteborn et al. 1995) and was recently highlighted by reports from the Rowett Institute in Scotland, which indicated adverse immunological and nutritional effects from enhanced lecithin in GM potatoes (Ewen and Pusztai 1999, Fenton et al. 1999). However, aspects of the former of these reports in particular were strongly criticised by a number of reputable scientific bodies as being unsubstantiated and have highlighted the need for agreed methodology in this field of research so that conclusive results can be acquired (Kuiper et al., 1999).

There has also been concern about genetically modified ingredients containing antibiotic resistance genes used to select transformed cells prior to the regeneration of transgenic plants. Use of these genes raises the potential for antibiotic-resistant strains of bacteria to develop via horizontal gene transfer in the gastro-intestinal tract of animals or even humans (Harding and Harris 1997). This possibility is not thought to be a major hazard since the antibiotic-resistant genes most often used for plant transformation themselves come from bacteria. They encode resistance against antibiotics rarely used in medicine such as kanamycin, against which a large percentage of gut micro flora is already resistant.

However, given the risk, however small, of producing more antibiotic resistant bacteria, techniques are being developed that will enable selectable markers to be removed from crop plants after the transformation process. Alternatives electable markers, not based on antibiotic selection, are also being tested, for example a mannose permease that allows the use of mannose, a sugar not normally available to plant metabolism, as a carbon source during plant regeneration.

Risk assessment methodology will also have to be adjusted for food plants which are modified to improve nutritional and other qualities, a major area for current and future research. Target traits include, for example, improving the nutritional value of proteins, increasing the concentrations of oils low in saturated fats, or fortification with micronutrients or antioxidants. Food plants modified in this way must undergo extensive toxicological and nutritional assessment with a combination of in vitro and in vivo tests, as currently required for all novel foods by the EU, for example. In the case of genetic modification, however, particular attention needs to be given to the detection and characterisation of potential unintended effects of modification. Inferences about such effects can no longer be based solely on chemical analysis of single macronutrients and micronutrients, and known crop-specific antinutrients or toxins. New methods have been developed to screen for potential alterations in the metabolism of the modified organism by such methods as:

• analysis of gene expression (monitored, for example, by microarray technology or mRNA fingerprinting)
• overall protein analysis (proteomics)
• secondary metabolite profiling.

Studies using these designs will need to be designed carefully to take account of the complexity of foods (OECD 1996, Note born et al. 2000, Van Hal et al. 2000).