Environmentalists disagree with animal liberationists over how to repair the relationship between human beings and other species. While this often comes as a surprise to those not deeply involved in either movement (or those like me who identify with both movements), the fact is that the agenda and values of each group sometimes contradict those of the other. For the purposes of this paper we can summarize the basic, conflicting intuitions of environmentalists and animal liberationists as follows: Environmentalists often argue that human consumption of animals is natural, and what is natural is permissible, and therefore human consumption of animals is permissible (hereafter this will be referred to as "the naturalistic argument"). Animal liberationists often argue that pain and death are evil, and that it is incumbent upon humans to eliminate evil to the extent that they can; therefore, it is incumbent upon humans to eliminate the pain and death that accompany the consumption of animals. In arguing against the vegetarian plank of animal liberation, some environmentalists have tried to strengthen the naturalistic argument with an appeal to the example of indigenous cultures in general and Native American cultures in particular. In this paper I will examine and criticize this strategy. However, I am not concerned here with defending animal liberationism. Rather, I would like to show how these arguments reveal-unintentionally, I am sure-an unflattering view of Native Americans and are damaging to Indians of the past, present, and future. It is my contention that environmentalists who argue by appealing to American Indian cultures tend to (1) characterize Indians of the past as noncultured, (2) characterize Indians of the present as culturally contaminated or nonexistent, (3) “disappear” important concerns of contemporary Indians, and (4) trivialize American Indian cultures. This critique is not to be construed as a denial of the power of American Indian cultures as models of environmental consciousness. Nor does anything written here against this particular line of ar ment imply the falsehood of the environmentalists’ belief in the permissibility of animal consumption (the fact that an argument is unsound or dangerous does not mean that its conclusion is false).

We hypothesized that small molecule transcriptional perturbation could be harnessed to target a cellular dependency involving protein arginine methyltransferase 5 (PRMT5) in the context of methylthioadenosine phosphorylase (MTAP) deletion, seen frequently in malignant pleural mesothelioma (MPM). Here we show, that MTAP deletion is negatively prognostic in MPM. In vitro, the off-patent antibiotic Quinacrine efficiently suppressed PRMT5 transcription, causing chromatin remodelling with reduced global histone H4 symmetrical demethylation. Quinacrine phenocopied PRMT5 RNA interference and small molecule PRMT5 inhibition, reducing clonogenicity in an MTAP-dependent manner. This activity required a functional PRMT5 methyltransferase as MTAP negative cells were rescued by exogenous wild type PRMT5, but not a PRMT5E444Q methyltransferase-dead mutant. We identified c-jun as an essential PRMT5 transcription factor and a probable target for Quinacrine. Our results therefore suggest that small molecule-based transcriptional perturbation of PRMT5 can leverage a mutation-selective vulnerability, that is therapeutically tractable, and has relevance to 9p21 deleted cancers including MPM.