The genetic sequence for a protein introduced in a plant is only functional when the DNA (gene) is activated in the plant. The presence of DNA in the diet is so common that it is of virtually no consequence to animals and people consuming plant-derived products. A recent publication describes experiments that directly tested whether extensive feeding of DNA to mice results in detectable expression of mRNA and protein in any of several organs of the animals (Holweg and Doerfler, 2001). Approximately 50 mg of DNA was fed to the mice per day. The DNA fed to the mice encoded the green fluorescent protein (GFP) under the control of one of three strong mammalian viral promoters [human cytomegalovirus (hCMV), Rous sarcoma virus (RSV) or simian virus 40 (SV-40)]. Separate experiments used a “gene therapy” approach with intramuscular injection into mice of the GFP gene coupled with either the hCMV promoter (pEGFP-C1) or the RSV promoter. These gene therapy studies showed clearly detectable expression of the GFP protein and mRNA at the site of injection. By comparison, no GFP protein or mRNA expression was detectable in liver, spleen, blood or intestinal epithelia of 21 animals fed the exact same DNA over a three week period. Also, fragments of the GFP gene were not detectable by PCR analysis of DNA isolated from spleen, liver or tail tip samples from either this three week feeding study or a separate experiment that involved feeding 50 mg of the pEGFP-C1 DNA per day to mice over eight generations. Therefore, it can be concluded from these studies that gene/promoter constructs clearly capable of functioning in vivo when administered via a gene therapy procedure (e.g. intramuscular injection) do not lead to gene expression in somatic cells or detectable integration into the germline of animals when provided orally.

In addition to digestive processes that degrade DNA, feed-processing procedures (and food preparation methods) significantly degrades DNA, especially those that involve heating to temperatures greater than 95°C (200°F) (Forbes et al., 2000; Gawienowski et al.). For example, the stability of transgenic DNA in maize preserved as silage has been studied (Hupfer et al., 1999). The intact transgene was only detectable during the first five days of ensiling; with small fragments (about 200 bp) of DNA being identifiable using sensitive PCR methods for longer stored silage. The rapid breakdown of DNA during ensiling was not unexpected. This process creates a harsh environment that involves plant tissue being chopped which leads to cell breakage, release of cell contents including the DNA and nucleases, and mild acidic conditions from natural fermentation. Thus, feed generated by ensilage reduces an animal’s dietary exposure to intact DNA, including any introduced transgenic DNA, even before ingestion and further degradation by its own digestive system.

Uptake of ingested DNA by intestinal flora causes some to ask if foreign DNA could persist in mammals. The possibility of plasmid DNA being incorporated via a normal biological process into endogenous gut bacteria is minimized due to the non-conjugative nature of typical plasmids used in recombinant DNA laboratories (Hamer, 1977) and the low frequency with which unaided transformation (uptake of naked DNA) occurs. Furthermore, beyond the difficulty of unaided transformation is the lack of stable incorporation (Behr et al., 1989) for DNA in general. Moreover, the probability of transferring such plasmids into natural bacteria in the gut environment has been calculated to be less than one in one million (Maniatis et al., 1982). Both scenarios assume the plasmid is free rather than incorporated into the plant genome, which would require that DNA be precisely removed and that it would be removed in a form that was similar enough that it could be incorporated into the animal genome.

There is also no evidence for the transfer of intact genes to humans from bacteria in the gut or from any food source (The Royal Society, 1998). The DNA remaining after digestion is small random pieces of DNA regardless of the food source. So the fundamental question is related to whether such DNA will be incorporated into the host cells in a functional way. There is no precedence for DNA being incorporated into host cells beyond the use of the basic nucleotide building blocks as nutrients. And, in fact, acid hydrolysis in the stomach is expected to depurinate most adensine and guanine nucleotides, which would result in a DNA sequence that would have very little value (Klinedinst and Drinkwater, 1992).