that happen to carry the proper gene combination (Gould 1986a, b; Roush 1997). The development of resistance may be delayed by the use of several toxins with different modes of action (Zhu et al. 1994; Jach et al. 1995). The toxins could arise from a combination of conventional breeding and transgenic techniques. However, even if the target sites of two toxins differ, there is still the possibility of cross resistance if the two toxins can be detoxified by the same enzymes. The new high-dose refuge approach (approach 1) has been the most widely accepted tactic for resistance management of target pests of transgenic or conventional pest-protected plants. Approaches 3 and 4 also have potential applicability. Approach 3, which relies on an interaction between the GMPP plant and natural enemies, is expected to decrease the rate of evolution of adaptation because it does not result in a major decrease in the fitness of either susceptible or adapted pests. Companies have not embraced this approach, because it cannot always be relied on to protect the crop, and they may have liability for control failures. There have also been concerns that the approach might not always inhibit evolution of adaptation to the pest-protected plant (for example, Johnson et al. 1997a, b). Approach 4 would also decrease the rate of evolution of resistance because only the fraction of the pest population that feeds on the protected-plant parts would be killed. This general approach could be useful if correctly implemented, but technological and ecological problems must be solved before it can be used (Roush 1997).
The high-dose approach is feasible with Bt toxins because even at high doses no health or environmental problems have been reported in commercially grown varieties. Also, crop yield has not been reduced by production of high doses. That might not be the case with some other plant-protection mechanisms.
Much of the theory of resistance management for GMPP plants has been developed for diploid, sexually reproducing organisms (NRC 1986; Roush and Tabashnik 1990). The theory is therefore only partially applicable to viruses, bacteria, and even a large group of insects that have different means of reproduction.
Plant pathologists have long been concerned with viral, fungal, and bacterial adaptation to conventional pest-protected plants. In the 1950s they developed the concept of GMPP plants having either vertical or horizontal resistance to pathogens (Van der Plank 1963). Vertical resistance typically involved single plant genes that were initially very effective at mitigating a disease but were expected to be evolutionarily overcome by rapid genetic shifts in the pathogen (Lamberti et al. 1981). Horizontal resistance was typically controlled by many genes, offered lower but adequate suppression of the target pathogen, and was expected to be more durable (recalcitrant to pathogen adaptation). This system for