rigid “checklist” approach suggesting specific data needed for petitions. While such data requirements might be convenient from the regulator’s viewpoint, this approach could be perceived as onerous busywork from the applicant’s perspective, and as an indication of bureaucratic rubber stamping from the activist communities’ perspective.
Beyond simple identification information, the only information provided to APHIS should be useful in identifying and determining risk. The data required of APHIS should be associated with the product (phenotype), not the process. Details of the molecular biology of the transgenic organism are helpful only when they define the phenotype of that organism in the context of exploring a potential risk. For example, it is important that APHIS be provided with the complete sequence of expressed transgenes in order to provide assurance that only the coding sequences of interest will be expressed in the transgenic plant. Evidence to date indicates that molecular gene transfer techniques often give complicated insertions of the transgene into the genome. Transgenics can be selected, however, that give Mendelian ratios and behave genetically in a normal single-gene fashion. Nevertheless, instead of a straightforward insertion of an unmodified DNA sequence, the transgene may be inserted in a rearranged manner, as multiple copies, or both. Recent studies have shown that host DNA of unknown origin may separate transgenes or parts thereof (Takano et al. 1997; Kohli et al. 1998, 1999; Pawlowski and Somers 1998; Jackson et al. 2001). An open reading frame (ORF) can be created (Somers, 2001, University of Minnesota, personal communication) at some point in the process of transfer or insertion.
The possibility exists that an ORF could lead to expression, although the likelihood is remote that such an RNA or subsequent protein product, if produced, could have any negative consequences. As cloning technologies improve, however, the ideal would be to clone all transgene components and be certain that no unexpected gene products would be produced. At present, cloning the complex insertion(s) is not a trivial matter. However, it would seem prudent to encourage the sequencing of inserts whenever possible and to include such information for review by the appropriate regulatory agency. Striving for a gene transfer technology that provides simpler inserts is important for the future. Agrobacteriummediated gene transfer may provide simpler insertions than particle bombardment, and new ideas on how to further reduce disruptive events in the transformation process are emerging (Koprek et al. 2001). Gene replacement technologies may become common in the future and perhaps alleviate the concern of producing new ORFs. Of course, spontaneous gene mutation happens at a low frequency, so any sequence can occasionally be modified to produce a new ORF. How often this happens in nontransgenics is not known.