Ethnographic Approaches in Primatology.

The shared evolutionary histories and anatomical similarities between humans and non-human primates create dynamic interconnections between these alloprimates. In this foreword to Folia Primatologica's special issue on "Ethnographic Approaches in Primatology," we review the ethnographic method and existing literature at the intersection of primatology and ethnography. We summarize, compare and contrast the 5 contributions to this special issue to highlight why the human-non-human primate interface is a compelling area to investigate via ethnographic approaches and to encourage increased incorporation of ethnography into the discipline of primatology. Ethnography is a valuable and increasingly popular tool with its use no longer limited to anthropological practitioners investigating traditional, non-Western peoples. Scholars from many disciplines now use ethnographic methods to investigate all members of our globalised world, including non-humans. As our closest living relatives, non-human primates (hereafter "primates") are compelling subjects and thus appear in a range of contexts within ethnographic investigations. The goal of this special issue is to highlight the trajectory of research at the intersection of primatology and ethnography and to illustrate the importance of ethnographic methods for the advancement of primatology as a discipline.

On the Rocks: Using Discourse Analysis to Examine Relationships between Barbary Macaques (Macaca sylvanus) and People on Gibraltar.

Primates are difficult to categorise due to some of the human-like characteristics they possess. Here, we examine the complexities that exist in a commensal relationship between an introduced population of Barbary macaques and local human populations on Gibraltar. In Western culture, much has been done to recognise primates' human characteristics while simultaneously focusing on keeping them at a metaphorical distance. In the context of Gibraltar's Barbary macaques, the anomalous status of primates causes a duality of perception whereby the macaques' position makes them both more frustrating and perceived as more worthy of protection. We examine the language used by Gibraltar residents about the macaques, interpreting statements using discourse analysis to reveal the complexities of people's perceptions of the macaques. Our results indicate that Barbary macaques on Gibraltar occupy a perceptual context of internal conflict in which they are viewed both with pride and a sense of ownership as well as with mistrust and fear. The relationship between people and Barbary macaques on Gibraltar is complex, and while sensitisation programmes and awareness-raising efforts exist, we recommend greater collaboration with residents to prevent the development of more intense negative human-macaque interactions.

Antibiotic-mediated chemoprotection enhances adaptation of E. coli PNP for herpes simplex virus-based glioma therapy.

The E. coli PNP suicide gene sensitizes solid tumors to nucleoside prodrugs, such as 6-methylpurine-2'-deoxyriboside (MeP-dR). In this study using lentiviral, MuLv, and HSV-based gene transfer, we quantified thresholds for inhibition of tumor growth and bystander killing by E. coli PNP and tested the role of intestinal flora in this process. Regressions of human glioma tumors following retroviral transduction exhibited dose dependence on both the level of PNP expression and the dose of MeP-dR administered, including strong tumor inhibition when 90-99% bystander cells comprised the tumor mass. A replication competent, non-neurovirulent herpes simplex virus (HSV) deficient in both copies of the gamma-1 34.5 gene was next engineered to express E. coli PNP under the egr-1 promoter (HSV-PNP). HSV-PNP injected intratumorally (17 million pfu/0.05 ml) in nude mice bearing 300 mg human glioma flank tumors produced a delay in tumor growth (approximately 24 days delay to one doubling). MeP-dR treatment after antibiotic therapy (to eliminate enteric flora encoding PNP enzymes) resulted in antitumor enhancement, with arrest of tumor growth (delay to doubling >50 days). Bystander killing of the magnitude described here has been difficult to accomplish with other suicide genes, such as HSV-tk or cytosine deaminase. The results establish a model for applying E. coli PNP to HSV treatment of glioma.

A long-acting suicide gene toxin, 6-methylpurine, inhibits slow growing tumors after a single administration.

We have demonstrated antitumor activity against refractory human glioma and pancreatic tumors with 6-methylpurine (MeP) using either a suicide gene therapy strategy to selectively release 6-methylpurine in tumor cells or direct intratumoral injection of 6-methylpurine itself. A single i.p. injection in mice of the prodrug 9-beta-D-[2-deoxyribofuranosyl]-6-methylpurine (MeP-dR; 134 mg/kg) caused sustained regression lasting over 70 days of D54 (human glioma) tumors transduced with the Escherichia coli purine nucleoside phosphorylase (PNP), and a single intratumoral injection of 6-methylpurine (5-10 mg/kg) elicited prolonged delays of the growth of D54 tumors and CFPAC human pancreatic carcinoma. Because the D54 tumor doubling time is >15 days, the experiments indicate that prodrug activation by E. coli PNP engenders destruction of both dividing and nondividing tumor compartments in vivo and, therefore, address a fundamental barrier that has limited the development of suicide gene strategies in the past. A prolonged retention time of 6-methylpurine metabolites in tumors was noted in vivo (T(1/2) >24 h compared with a serum half-life of <1 h). By high-pressure liquid chromatography, metabolites of [(3)H]MeP-dR were 5- to 6-fold higher in tumors expressing E. coli PNP. These experiments point to new endpoints for monitoring E. coli PNP suicide gene therapy, including intratumoral enzymatic activity, in situ (intratumoral) prodrug conversion, and tumor regressions after direct injection of a suicide gene toxin. The findings also help explain the strong in vivo bystander killing mechanism ascribed by several laboratories to E. coli PNP in the past.