Chapter 9 Which Patient Takes Centre Stage?

The growth of personalised medicine and patient partnerships in biomedical research are reshaping both the emotional and material intersections between human patients and animal research. Through tracing the creative work of patients, publics, scientists, clinicians, artists, film-makers, and campaigning groups this chapter explores how ‘patient voices’ are being rearticulated and represented around animal research. The figure of ‘the patient’ has been a powerful actor in arguments around animal research, mostly ‘spoken for’ by formal organisations, especially in publicity material making ethical justifications for the need and funding of medical research. Here, patient voices make corporeal needs legible, gather expectations and resources, and provide the horizon for embodying future hopes. However, the accessibility of digital media, alongside local institutional experiments in openness, is creating alternative spaces for voicing patient interfaces with animal research. On research establishment websites, and elsewhere, patients’ perspectives are emerging in short films, taking up positions as narrators, tour guides, and commentators, inviting the public to follow them into these previously inaccessible spaces. The embodied experience of patients, sometimes severely affected by the current absences in biomedical research, are used to authorise their presence in these places, and allow them to ask questions of animal researchers. The films are powerful and emotional vehicles for voicing patient experiences and opening up animal research. They also refigure the affective responsibilities around animal research, resituating a public debate around ethics within the body of the patient. The future expectations personified in the abstract figure of the patient, are rendered turbulent in the ambiguous corporeal encounter between human and animals undergoing similar experiences of suffering

Intermittent Escherichia coli O157:H7 colonisation at the terminal rectum mucosa of conventionally-reared lambs§

In cattle, the lymphoid rich regions of the rectal-anal mucosa at the terminal rectum are the preferred site for Escherichia coli O157:H7 colonisation. All cattle infected by rectal swab administration demonstrate long-term E. coli O157:H7 colonisation, whereas orally challenged cattle do not demonstrate long-term E. coli O157:H7 colonisation in all animals. Oral, but not rectal challenge of sheep with E. coli O157:H7 has been reported, but an exact site for colonisation in sheep is unknown. To determine if E. coli O157:H7 can effectively colonise the ovine terminal rectum, in vitro organ culture (IVOC) was initiated. Albeit sparsely, large, densely packed E. coli O157:H7 micro-colonies were observed on the mucosa of ovine and control bovine terminal rectum explants. After necropsy of orally inoculated lambs, bacterial enumeration of the proximal and distal gastrointestinal tract did suggest a preference for E. coli O157:H7 colonisation at the ovine terminal rectum, albeit for both lymphoid rich and non-lymphoid sites. As reported for cattle, rectal inoculation studies were then conducted to determine if all lambs would demonstrate persistent colonisation at the terminal rectum. After necropsy of E. coli O157:H7 rectally inoculated lambs, most animals were not colonised at gastrointestinal sites proximal to the rectum, however, large densely packed micro-colonies of E. coli O157:H7 were observed on the ovine terminal rectum mucosa. Nevertheless, at the end point of the study (day 14), only one lamb had E. coli O157:H7 micro-colonies associated with the terminal rectum mucosa. A comparison of E. coli O157:H7 shedding yielded a similar pattern of persistence between rectally and orally inoculated lambs. The inability of E. coli O157:H7 to effectively colonise the terminal rectum mucosa of all rectally inoculated sheep in the long term, suggests that E. coli O157:H7 may colonise this site, but less effectively than reported previously for cattle

Investigation of porcine interferons as a metaphylactic intervention against classical swine fever virus

Classical Swine Fever (CSF) is an important viral disease of swine. The application of Interferon (IFN) via viral vectors could be a beneficial intervention strategy against CSFV. Unlike type I and II IFN, the anti-CSFV activity of type III IFNs is unknown. Type III IFNs have similar antiviral actions to type I IFNs, but their specific receptors have limited tissue distribution and may be important as very early defences against infection at epithelial surfaces. PoIFN (type I (α, β) type II (γ) and type III (λ1, 3)) were cloned into a mammalian expression vector, expressed in porcine tracheal (NpTr) cells and the induction of an immune response and anti-CSFV activity examined. PoIFNs were subsequently expressed using adenovirus and MVA viral vectors and their antiviral activity assessed. All three types of vectored IFN upregulated expression of the interferon stimulated gene MxA and significantly reduced CSFV infection in the NpTr cell line and in porcine primary cells. Inoculation of NpTr cells with adenovirus and MVA vectors expressing all three types of IFN inhibited CSFV infection, with the Ad_IFNα/β and λ constructs inducing a greater anti- CSFV effect than the Ad_IFNγ constructs. Intranasal and intramuscular inoculations with MVA vectors did not induce ISG upregulation in the tonsils or protect monocytes against an ex vivo CSFV challenge. These outcomes are not likely to be true reflections on the potential of this vector system due to limitations in the preparation of inoculum. Intranasal inoculation with adeno vectors expressing type I and type III IFN did not induce any significant systemic or tissue specific antiviral responses and under these conditions would not be predicted to offer successful protection against CSFV infection. Intramuscular inoculation of Ad_IFNα into pigs induced upregulated serum IFNα levels and offered significant levels of protection against ex vivo CSFV challenge of isolated leukocytes and offers a promising candidate for metaphylactic intervention.Open Acces

The Mouse Exchange: What can curiosity-driven public engagement activities contribute to dialogues about animal research?

Despite efforts by the industry to be more open about the use of animals in research, opportunities for the public to learn about this are limited by the traditional public engagement format, which typically follows a knowledge-deficit approach. Coupled with barriers around public willingness to learn about something that stirs up complex feelings, there is a need to develop new public engagement activities that allow for open, nuanced, curiosity-driven explorations of animal research. The Mouse Exchange (MX) achieves this by allowing participants to feel in control of their experience, and to explore the hesitancy, distrust, suspicion, anxieties, and guilt that some associate with animal research. The MX approaches openness via focusing on the making and supply of animals used in research, rather than on the experiment itself. The MX has no script, but rather creates a space where participants converse and craft, becoming curious, creative, and imaginative about the topic as a research mouse, stitched together from felt fabric, forms in their hands. Through this process of crafting, an attachment can form between maker and mouse that gives participants a different stake in animal research. We argue that the MX offers a new, valuable approach to engaging publics in discussions around animal research

Chapter 9 Which Patient Takes Centre Stage?

The growth of personalised medicine and patient partnerships in biomedical research are reshaping both the emotional and material intersections between human patients and animal research. Through tracing the creative work of patients, publics, scientists, clinicians, artists, film-makers, and campaigning groups this chapter explores how ‘patient voices’ are being rearticulated and represented around animal research. The figure of ‘the patient’ has been a powerful actor in arguments around animal research, mostly ‘spoken for’ by formal organisations, especially in publicity material making ethical justifications for the need and funding of medical research. Here, patient voices make corporeal needs legible, gather expectations and resources, and provide the horizon for embodying future hopes. However, the accessibility of digital media, alongside local institutional experiments in openness, is creating alternative spaces for voicing patient interfaces with animal research. On research establishment websites, and elsewhere, patients’ perspectives are emerging in short films, taking up positions as narrators, tour guides, and commentators, inviting the public to follow them into these previously inaccessible spaces. The embodied experience of patients, sometimes severely affected by the current absences in biomedical research, are used to authorise their presence in these places, and allow them to ask questions of animal researchers. The films are powerful and emotional vehicles for voicing patient experiences and opening up animal research. They also refigure the affective responsibilities around animal research, resituating a public debate around ethics within the body of the patient. The future expectations personified in the abstract figure of the patient, are rendered turbulent in the ambiguous corporeal encounter between human and animals undergoing similar experiences of suffering

The Mouse Exchange Toolkit

The Mouse Exchange is an award-winning, curiosity-led crafting and conversation activity that creates a non-confrontational space to relate to research animals and to talk about research animal lives. This is a guide for facilitators who would like to use the Mouse Exchange in their teaching, internal organisational conversations about animal research or for external engagement with the public

Animal research nexus: a new approach to the connections between science, health and animal welfare

Animals used in biological research and testing have become integrated into the trajectories of modern biomedicine, generating increased expectations for and connections between human and animal health. Animal research also remains controversial and its acceptability is contingent on a complex network of relations and assurances across science and society, which are both formally constituted through law and informal or assumed. In this paper, we propose these entanglements can be studied through an approach that understands animal research as a nexus spanning the domains of science, health and animal welfare. We introduce this argument through, first, outlining some key challenges in UK debates around animal research, and second, reviewing the way nexus concepts have been used to connect issues in environmental research. Third, we explore how existing social sciences and humanities scholarship on animal research tends to focus on different aspects of the connections between scientific research, human health and animal welfare, which we suggest can be combined in a nexus approach. In the fourth section, we introduce our collaborative research on the animal research nexus, indicating how this approach can be used to study the history, governance and changing sensibilities around UK laboratory animal research. We suggest the attention to complex connections in nexus approaches can be enriched through conversations with the social sciences and medical humanities in ways that deepen appreciation of the importance of path-dependency and contingency, inclusion and exclusion in governance and the affective dimension to research. In conclusion, we reflect on the value of nexus thinking for developing research that is interdisciplinary, interactive and reflexive in understanding how accounts of the histories and current relations of animal research have significant implications for how scientific practices, policy debates and broad social contracts around animal research are being remade today.</p

Purified galactooligosaccharide, derived from a mixture produced by the enzymic activity of Bifidobacterium bifidum, reduces Salmonella enterica serovar Typhimurium adhesion and invasion in vitro and in vivo

The prebiotic Bimuno (R) is a mixture containing galactooligosaccharides (GOSs), produced by the galactosyltransferase activity of Bifidobacterium bifidum NCIMB 411 71 using lactose as the substrate Previous in vivo and in vitro studies demonstrating the efficacy of Bimuno (R) in reducing Salmonella enterica serovar Typhimurium (S Typhimurium) colonization did not ascertain whether or not the protective effects could be attributed to the prebiotic component GOS Here we wished to test the hypothesis that GOS, derived from Bimuno (R) may confer the direct anti-invasive and protective effects of Bimuno (R) In this study the efficacy of Bimuno (R), a basal solution of Bimuno (R) without GOS [which contained glucose, galactose, lactose, maltodextrin and gum arabic in the same relative proportions (w/w) as they are found in Bimuno (R)] and purified GOS to reduce S Typhimurium adhesion and invasion was assessed using a series of in vitro and in vivo models The novel use of three dimensionally cultured HT-29-16E cells to study prebiotics in vitro demonstrated that the presence of similar to 5 mg Bimuno (R) ml(-1) or similar to 2 5 mg GOS ml(-1) significantly reduced the invasion of S Typhimurium (SL1344nal(r)) (P<0 0001) Furthermore, similar to 2 5 mg GOS ml(-1) significantly reduced the adherence of S Typhimurium (SU 344nal(r)) (P<0 0001) It was demonstrated that cells produced using this system formed multi-layered aggregates of cells that displayed excellent formation of brush borders and tight junctions In the murine ligated deal gut loops, the presence of Bimuno (R) or GOS prevented the adherence or invasion of S Typhimurium to enterocytes, and thus reduced its associated pathology This protection appeared to correlate with significant reductions in the neutral and acidic mucins detected in goblet cells, possibly as a consequence of stimulating the cells to secrete the mucin into the lumen In all assays, Bimuno (R) without GOS conferred no such protection, indicating that the basal solution confers no protective effects against S Typhimurium Collectively, the studies presented here clearly indicate that the protective effects conferred by Bimuno (R) can be attributed to GO