## 1 Bt Insecticidal Proteins Are Not Detrimental to Most Invertebrates and Vertebrates  
_Bacillus thuringiensis_ (Bt) has been widely used in the field for more than 60 years and has a long history of safe usage. Since the mid-1990s, transgenic crops expressing Bt toxins for pest resistance have also been increasingly deployed--with the additional benefit of reduced usage of conventional broad-spectrum pesticides that have potential deleterious effects [1, 2]. Extensive safety tests have been carried out in order to licence products for use and, in addition, a wide range of laboratory and field experiments have been performed to analyse factors such as host range, mechanisms of action, processing and activation, target specificity, receptor binding, off-target effects, insect resistance and safety. The overall message from this extensive literature is that Bt and products derived from it are safe, showing selectivity for a very limited number of targets [3, 4]. Even within narrow taxonomic divisions, toxins are able to discriminate between individual species that they are able to affect and those that are refractory (see below).  
Against this background, the recent paper published in this journal by [PERSON] [5] proposes that alkaline foregents in a range of herbivores may have evolved to deal with dietary latex and, at the same time, that this increases their susceptibility to endotoxins from _Bacillus thuringiensis_ (Bt). Whether or not latex is likely to be a driver of gut adaptations will not be addressed here, except to note that a range of other factors may also underpin the evolution of physiological conditions in the gut. For example, adaptation of gut pH in a range of insects in the order Lepidoptera has been proposed as a response to the relative intake of dietary tannins [6]. Beyond proposals linked to latex in diets, the [PERSON] paper also makes a number of general statements about the susceptibility of alkaline midguts to delta-endotoxins derived from Bt and other bacteria. Statements generalising about Bt toxins are hard to justify and should be avoided. Bt toxins belong to at least 10 distinct structural classes (plus proteins currently classed under the holding name Xpp since structural data are not available at present [7]). Even if the consideration is limited to the proteins produced as natural crystals, a wide variety of proteins are also encompassed (App, Cyt, Cry, Gpp, Mpp, Tpp structural classes and Xpp proteins). This means that general statements cannot be substantiated across this range of proteins and their different mechanisms of action. Thus, [PERSON]'s hypotheses lack details and are overly simplistic.  
While there are some minor errors in the description of toxins (the Mtx toxins of _Lysini-bacillus sphaericus_, now classified as either Mtx or Mpp proteins [7], are mischaracterised as sporulation, rather than vegetatively produced proteins), the major concern with the paper is the number of statements and generalisations that imply a general susceptibility of animals with alkaline foreguts to Bt and its toxins and implications for safety. A review of the literature shows that these proposals are not correct.