Abstract
In my STS research paper, I discuss the ethics and policy of euthanasia of animals in laboratories for biomedical research. Animals are used in laboratory research as simplified yet comparable models of human physiology that can provide valuable information about disease progression and treatment. Euthanasia is used to end animal lives with the goal of preventing pain and further suffering. This is typically done when animals must die for the research, but can also be done at humane endpoints or if animals are in pain. I explore the ways ethical and regulatory factors influence animal euthanasia methods in biomedical research laboratories to gain a deeper understanding of the nuances of scientific animal use. I describe how researchers, policy, policymakers, regulatory bodies, activists, and other social groups have different perspectives and influences on the technology. Researchers, for instance, perform the euthanasia and are responsible for following regulations. Regulators, though, influence which euthanasia methods can be used and which are recommended. Regulations exist at national and institutional levels, with the Animal Welfare Act governing the overall treatment of animals in research and documents such as the AVMA Guidelines for the Euthanasia of Animals establishing proper protocols. At the institutional level, IACUCs, similar to IRBs, maintain protocols and ensure compliance with all regulations. Regulations influence the practices of research as following them dictates funding, ethics, and qualification. From an ethics perspective, euthanasia must cause death without additional pain. Therefore, acceptable methods of euthanasia in regulations must ensure no suffering, be fast, and avoid a fear response. Ethics drive the involved social groups to make choices they believe morally correct, whether it be through choices of acceptable euthanasia methods based on current pain research or choices to avoid animal use in research where not absolutely necessary.
In my technical project, we explore microvascular dysfunction in two highly prevalent diseases: diabetes and Alzheimer’s disease. The central nervous system microvasculature is impacted in both disease contexts, including in the change of the integrity of blood-brain- and blood-retina-barriers, decreased blood flow, and inflammation. There is also associated comorbidity between both diseases, but these comorbidities and microvascular behaviors are not fully understood. We explore the phenomenon of pericyte bridging, or the separation of pericytes—specialized support cells that wrap around capillaries—from their associated vessel. Pericyte bridging has been seen in hyperglycemic retina, but has not yet been observed in the brain in hyperglycemia or in either tissue in Alzheimer’s disease. This project investigates pericyte bridging, as well as the coverage of laminin—a basement membrane protein— and the coverage of Amyloid beta—plaque protein deposits which are a hallmark of Alzheimer’s disease— to provide insight into greater microvascular dysfunction in diseases. First, we optimized a staining panel to visualize vasculature, pericytes, laminin, and Amyloid beta on the same tissue (both retina and brain). Then, with the use of the optimized staining panel, we gathered quantitative data manually for each of four conditions: hyperglycemia, Alzheimer’s disease, comorbid, and vehicle. The manual quantification, though, is low-throughput and highly subjective. Thus, the second piece of our project created a novel analytical pipeline for confocal image analysis. The pipeline begins with the user adjusting channels for brightness and contrast in ImageJ. Then, Peri takes the image, identifies individual pericytes, crops each individual pericyte at a standard radius, saves the crops as PNGs, then uses a Convolutional Neural Network to recognize and tally bridging and quiescent pericytes. The model aims to increase throughput, accuracy, and objectivity of identifying and classifying pericytes as bridging or quiescent to answer more research questions regarding microvascular dysfunction. With the completed model, we compare the manual quantification of pericyte bridging with the automated quantification to determine validity of the pipeline. Together, the pipeline, experimental data, and optimized staining provide context into how pericyte morphology may impact greater microvascular dysfunction in the central nervous system.
My STS research paper and technical project are directly related. My technical project requires laboratory mice be euthanized and their retinas and brains be harvested to perform immunohistochemistry and draw conclusions on microvascular changes in disease. This is an example of animals being euthanized to increase human knowledge of a physiological phenomenon in diseases like diabetes and Alzheimer’s disease. This project required an animal care and use protocol that falls under the IACUC at UVA and the euthanasia method and procedure had to be in compliance with all relevant regulations. I was able to use the technical project to see the point of view of the researcher in animal euthanasia use, and use the STS project to understand the other social groups involved.
