(Excerpt from: Assessing the safety and nutritional quality of genetically engineered foods by John Fagan)
There exist several mechanisms by which allergens could be expressed in foods through genetic engineering. A number of molecular mechanisms have also been identified through which the genetic manipulation of food producing organisms could generate new allergens or increase the allergenicity of proteins normally present in food producing organisms. Because allergen-carrying transgenic foods will in most cases maintain the appearance of their natural, non allergenic counterparts, they pose a serious hazard to the consumer. Consumers will not be able to avoid these allergenic foods, because they will not be able to distinguish them from the corresponding natural foods. The labeling of all genetically engineered foods would, of course, solve this problem and would also make it possible for health authorities to trace allergen problems that arise.
At present, empirical evidence regarding the generation of allergenic foods through genetic engineering is sparse, since few of the genetically engineered foods now under development have been thoroughly tested for allergenicity. However, one example has already come to light: Pioneer Hybrid has developed soybeans with nutritionally balanced amino acid composition. They accomplished this by engineering into these beans the gene for a brazil nut storage protein. However, this protein turns out to be allergenic to a significant proportion of the population. Pioneer Hybrid has wisely decided to terminate plans to commercialize this product.
In addition to this limited empirical evidence regarding potential allergenicity of recombinant foods, a consideration of the mechanics of recombinant DNA manipulations and the fundamental principles of immunology, biochemistry, cell biology, molecular biology, and physiology uncovers a number of straightforward mechanisms by which genetic manipulations can alter the function of food producing organisms such that they express allergens. Based on this analysis, it is clear that genetic manipulations are capable of generating allergenic foods. The probability of such events is small but it is finite. Thus the risk of encountering dangerous allergens in novel transgenic foods is a very real one. The following are the most obvious mechanisms by which the use of recombinant DNA techniques could generate new food allergens:
(a) It is known that many foods contain components that are low level allergens or immuno-irritants. At these low levels they produce negligible or minor problems. As discussed earlier, when recombinant DNA techniques are used to introduce new genes into a food producing organism, those manipulations can inadvertently alter the levels of proteins that are normally present in that organism. If the expression of an allergen or immuno-irritant increases substantially, it may reach concentrations within the food that could induce serious allergenic responses.
In some cases, genes will be used in the development of transgenic food producing organisms that are derived from sources known to commonly cause allergic reactions. In such cases, foods derived from such GEOs should be assumed to be allergenic unless empirical evidence demonstrates that this is not the case. If positive evidence excluding allergenicity cannot be obtained, it is obviously necessary to label the transgenic food as potentially allergenic to alert sensitive consumers. In cases where the allergic reaction might be life threatening, such foods should not be introduced into the market place.
(b) Many of the recombinant proteins that will be expressed in food producing organisms are proteins that are not normally present in the food supply. Thus their potential allergenicity is unknown. There is a reasonable probability that some of these proteins will be allergenic. It should be pointed out that, since even trace amounts of some allergens are sufficient to induce powerful allergenic reactions, the fact that a genetically engineered substance may be present in only trace amounts does not necessarily eliminate the possibility that it could be allergenic. Because individuals will probably not have been previously sensitized to these new allergens, they will probably not elicit a powerful allergenic response on first exposure. However, if such an allergen becomes a common component of the food supply, allergenicity will develop as exposure continues.
(c) Recombinant modifications could alter the primary or secondary structure of some proteins in such a way as to increase their allergenicity or cause them to become allergenic. Thus, even though a protein may be commonly present in food and not allergenic, when recombinant DNA techniques are used to alter the gene encoding that protein, the resultant recombinant protein could be allergenic.
This is especially the case with fusion proteins, expressed from genes generated by linking pieces of coding sequences from two or more sources. These are proteins consisting of peptide segments derived from two or more proteins. This is accomplished by using recombinant DNA techniques to fuse together pieces of the genes for those proteins. The potential allergenicity of fusion proteins cannot be deduced from the properties of the parental proteins from which they are derived, and thus cannot be predicted or modeled. This is because the domains where two proteins are joined can assume conformations very different from those of either of the original proteins. Furthermore, the likelihood of generating allergenicity in fusion proteins is increased by the fact that the junctions at which two proteins are fused often assume secondary and tertiary structures that are not common in natural proteins, and are, therefore, more likely to be allergenic.
(d) Even though recombinant proteins will often be expressed in food-producing organisms at low levels compared to the total protein content of a food, it is likely that even these levels will be substantially higher-orders of magnitude higher in some cases-than the naturally-occurring levels of those proteins. Thus, even if previous research fails to uncover evidence for allergenicity, a protein may behave as an allergen when expressed at higher levels through genetic engineering.
(e) Different organisms possess different biochemical mechanisms for the processing of newly synthesized proteins. Therefore, a recombinant protein may be processed differently in the genetically engineered recipient organism than it was in the organism from which the gene for that protein was isolated, and in which that protein is naturally expressed. These differences in processing could result in the transgenic form of the protein having different allergenic properties than the naturally occurring form.
The risk that new allergens can be generated during the process of genetically engineering food-producing organisms leaves the developer of such organisms in a difficult position with regard to safety testing, because there is no adequate approach for generalized testing for potential allergenicity short of human testing.
"Genetically Engineered Food - Safety Problems"