Which Vaccine? The Cost of Religious Freedom in Vaccination Policy

We discuss whether and under what conditions people should be allowed to choose which COVID-19 vaccine to receive on the basis of personal ethical views. The problem arises primarily with regard to some religious groups’ concerns about the connection between certain COVID-19 vaccines and abortion. Vaccines currently approved in Western countries make use of foetal cell lines obtained from aborted foetuses either at the testing stage (Pfizer/BioNTech and Moderna vaccines) or at the development stage (Oxford/AstraZeneca vaccine). The Catholic Church’s position is that, if there are alternatives, Catholic people have a moral obligation to request the vaccine whose link with abortion is more remote, which at present means that they should refuse the Oxford/AstraZeneca vaccine. We argue that any consideration regarding free choice of the vaccine should apply to religious and non-religious claims alike, in order to avoid religion-based discrimination. However, we also argue that, in a context of limited availability, considering the significant differences in costs and effectiveness profile of the vaccines available, people should only be allowed to choose the preferred vaccine if: 1) this does not risk compromising vaccination strategies; and 2) they internalize any additional cost that their choice might entail. The State should only subsidize the vaccine that is more cost-effective for any demographic group from the point of view of public health strategies.

Transforming trash to treasure Cultural ambiguity in foetal cell research

Background Rich in different kind of potent cells, embryos are used in modern regenerative medicine and research. Neurobiologists today are pushing the boundaries for what can be done with embryos existing in the transitory margins of medicine. Therefore, there is a growing need to develop conceptual frameworks for interpreting the transformative cultural, biological and technical processes involving these aborted, donated and marginal embryos. This article is a contribution to this development of frameworks. Methods This article examines different emotional, cognitive and discursive strategies used by neurobiologists in a foetal cell transplantation trial in Parkinson’s disease research, using cells harvested from aborted embryos. Two interviews were analysed in the light of former observations in the processing laboratories, using the anthropologist Mary Douglas’s concept of pollution behaviour and the linguist, philosopher, psychoanalyst and feminist Julia Kristeva’s concept of the abjective to explain and make sense of the findings. Results The findings indicate that the labour performed by the researchers in the trial work involves transforming the foetal material practically, as well as culturally, from trash to treasure. The transformation process contains different phases, and in the interview material we observed that the foetal material or cells were considered objects, subjects or rejected as abject by the researchers handling them, depending on what phase of process or practice they referred to or had experience of. As demonstrated in the analysis, it is the human origin of the cell that makes it abjective and activates pollution discourse, when the researchers talk of their practice. Conclusions The marginal and ambiguous status of the embryo that emerges in the accounts turns the scientists handling foetal cells into liminal characters in modern medicine. Focusing on how practical as well as emotional and cultural strategies and rationalizations of the researchers emerge in interview accounts, this study adds insights on the rationale of practically procuring, transforming and utilizing the foetal material to the already existing studies focused on the donations. We also discuss why the use and refinement of a tissue, around which there is practical consensus but cultural ambiguity, deserves further investigation.

Protocol for an open label: phase I trial within a cohort of foetal cell transplants in people with Huntington’s disease

Huntington’s disease is a progressive neurodegenerative disorder characterized by motor, cognitive and psychiatric symptoms. Currently, no disease-modifying therapies are available to slow or halt disease progression. Huntington’s disease is characterized by relatively focal and specific loss of striatal medium spiny neurons, which makes it suitable for cell-replacement therapy, a process involving the transplantation of donor cells to replace those lost due to disease. TRIal DEsigns for delivery of Novel Therapies in neurodegeneration is a phase I Trial Within a Cohort designed to assess safety and feasibility of transplanting human foetal striatal cells into the striatum of people with Huntington’s disease. A minimum of 18 participants will be enrolled in the study cohort, and up to five eligible participants will be randomly selected to undergo transplantation of 12–22 million foetal cells in a dose escalation paradigm. Independent reviewers will assess safety outcomes (lack of significant infection, bleeding or new neurological deficit) 4 weeks after surgery, and ongoing safety will be established before conducting each subsequent surgery. All participants will undergo detailed clinical and functional assessment at baseline (6 and 12 months). Surgery will be performed 1 month after baseline, and transplant participants will undergo regular clinical follow-up for at least 12 months. Evaluation of trial processes will also be undertaken. Transplant participants and their carers will be interviewed ∼1 month before and after surgery. Interviews will also be conducted with non-transplanted participants and healthcare staff delivering the intervention and involved in the clinical care of participants. Evaluation of clinical and functional efficacy outcomes and intervention costs will be carried out to explore plausible trial designs for subsequent randomized controlled trials aimed at evaluating efficacy and cost-effectiveness of cell-replacement therapy. TRIal DEsigns for delivery of Novel Therapies in neurodegeneration will enable the assessment of the safety, feasibility, acceptability and cost of foetal cell transplants in people with Huntington’s disease. The data collected will inform trial designs for complex intra-cranial interventions in a range of neurodegenerative conditions and facilitate the development of stable surgical pipelines for delivery of future stem cell trials. Trial Registration: ISRCTN52651778

Foetal Cell Transplantation for Parkinson’s Disease: Focus on Graft-Induced Dyskinesia

Transplantation of dopamine- (DA-) rich foetal ventral mesencephalic cells emerged as a promising therapy for Parkinson’s disease (PD), as it allowed significant improvement of motor symptoms in several PD patients in open-label studies. However, double-blind clinical trials have been largely disappointing. The general agreement in the field is that the lack of standardization of tissue collection and preparation, together with the absence of postsurgical immunosuppression, played a key role in the failure of these studies. Moreover, a further complication that emerged in previous studies is the appearance of the so-called graft-induced dyskinesia (GID), in a subset of grafted patients, which resembles dyskinesia induced by L-DOPA but in the absence of medication. Preclinical evidence pointed to the serotonin neurons as possible players in the appearance of GID. In agreement, clinical investigations have shown that grafted tissue may contain a large number of serotonin neurons, in the order of half of the DA cells; moreover, the serotonin 5-HT1A receptor agonist buspirone has been found to produce significant dampening of GID in grafted patients. In this paper, we will review the recent preclinical and clinical studies focusing on cell transplantation for PD and on the mechanisms underlying GID.

Quantification of Foetal Cells In Foetal Maternal Haemorrhage (FMH): Comparison of 3 Methods

Abstract 4406 Methods of quantification of foetal red cell in maternal blood samples are important to ensure the correct administration of prophylactic anti-D to prevent sensitisation of the mother which may result in haemolytic disease of the newborn and foetus in subsequent pregnancies. We aimed to assess the accuracy of 3 methods: a gel card technique using anti-D and 2 acid-elution techniques, foetal cell detection kit (FCD, Inverclyde Biologicals Lanarkshire, Scotland) and a kit from Clin-Tech Limited (Guildford, England) based on the Kleihauer-Betke foetal stain technique (KBT), to quantifiy foetal red cells in maternal samples. The sensitivity of the gel method was also assessed. A total of 63 maternal blood samples and 30 man-made control blood samples were analysed, with only 57 maternal samples confirmed to be Rh D negative. Rh D positive samples were excluded. All samples were run concurrently with the 3 methods, according to manufacturers’ instructions. Mann Whitney test was used to compare the results. The gel technique was recorded in terms of grading of agglutination while the acid-elution kits were recorded by degree of FMH (mL). Column agglutination was also used to assess sensitivity. Results showed only 3 maternal samples were positive for FMH using the acid-elution method but not the gel technique. Statistically there was no significant difference between the techniques (Mann-Whitney test). Sensitivity of the gel method showed that it has the ability to detected FMH of more than 3mL whilst the 2 kits were able to detect FMH of 1mL. The study showed that gel technique required little skill to perform but it was not considered suitable for accurate quantification of FMH and consequently for the correct administration of prophylactic anti-D. The foetal cell detection kit (Inverclyde Biologicals) showed a similar ability to detect and quantify FMH when compared to the Kleihauer –Betke kit (Clin-Tech) with better overall staining intensity. The Kleihauer-Betke test from Clin-Tech and the foetal cell detection kit from Inverclyde Biologicals showed no significant difference (p = 0.98), thus there is no statistical significant difference between the 2 methods. However, the sensitivity of the column agglutination method was lower, as significant agglutination could only be observed with FMH of more than 3mL. The expected values were plotted based on Gomez-Arbones et al (2002), who cited significant agglutination seen when FMH is 0.1% or about 2.5mL. Sensitivity was found to be less than expected as a higher amount of bleed is required to observed significant agglutination. The FMH sample representing 1–6mL was repeated and similar findings were recorded, as significant agglutination was only observed when FMH was 4mL. The column agglutination method is not suitable as a quantitative measurement of FMH as it only allows qualitative analysis, thus if it is incorporated into a clinical setting, it must be accompanied by a quantitative test. The foetal cell detection kit has similar staining capabilities to detect foetal cells and compared to Clin-Tech was easier to use as there is no need to prepare eluting solution unlike the latter. However, fixing solution was not provided and hence need to be prepared. Results showed that only 3 maternal samples were positive for the presence of FMH and thus using a semi-quatitative acid-elution technique should be sufficient in FMH quantification unless FMH using the acid-elution technique exceeds 2mL, as recommende,d by the BCSH guidelines (2009), then the sample should be analysed using flow cytometry. Acknowledgments: Central Manchester Hospitals Transfusion Laboratory for the provision of blood samples. Performed as part of MSc Biomedical Science project, funded by Mancheste Metropolitan University. Disclosures: No relevant conflicts of interest to declare.