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Whistleblowing in Biomedical Research and Medicine: An Analysis of Ethical Expectations and Dilemmas
Description
In biomedical research institutions and medical institutions alike, whistleblowing, or the reporting of misconduct, has been severely retaliated against. Whistleblowers report misconduct by adhering to institutional whistleblowing policies, and do so in order to maintain ethical practice within their institution; it is important to note that by taking this ethical action, whistleblowers are aiming to protect the future of biomedical research and medicine. Despite these intentions, whistleblowing has developed a negative stigma due to the misconception that whistleblowers have self-proclaimed authority and are unable to function as part of a team. The retaliation against whistleblowers has been connected to psychological and professional fallout for the whistleblower, and it has been found that many whistleblowers suffer as a direct result of a lack of institutional support. The problems with whistleblowing culture demonstrate issues surrounding how ethics are maintained in institutions, who ethics policies apply to, and who has authority. The retaliation seen against whistleblowers outlines inherent institutional failures, and highlights the need for institutional change in order to both promote ethical practice and protect the whistleblowers who adhere to ethics policies. This thesis discusses such failures in detail, and outlines several broad solutions in order to combat this issue.
ContributorsTaylor, Kylee Anne (Author) / Robert, Jason (Thesis director) / Ellison, Karin (Committee member) / Johnson, Nate (Committee member) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2019-05
Description
The concept of “good” research is concrete in terms of technique, but complex in theory. As technology advances, the complexity of problems we must solve also grows. Research is facing an ethical dilemma—which projects, applied or basic, should be funded. Research is no longer an isolated sector in society, and the decisions made inside of the laboratory are affecting the general public more directly than ever before. While there is no correct answer to what the future of research should be, it is clear that good research can no longer be only defined by the current classification system, which is rooted in antiquated, yet ingrained, social status distinctions.
Differences between basic and applied research were explored through a wet-lab case study. Vaccinia virus (VACV) infections are a prime model of the competition between a virus and its host. VACV contains a gene that is highly evasive of the host immune system, gene E3L. The protein encoded by E3L is E3, which contains two highly conserved regions, a C-terminus, and a N-terminus. While the C-terminus is well-understood, the mechanism by which the N-terminus grants IFN resistance was previously unknown. This project demonstrated that the N-terminus prevents the initiation of programmed necrosis through host-encoded cellular proteins RIP3 and DAI. These findings provide insight into the function of the N-terminus of E3, as well as the unique functions of induced programmed necrosis.
This project was an example of “basic” research. However, it highlights the interconnectivity of basic and applied research and the danger in isolating both projects and perspectives. It points to the difficult decisions that must be made in science, and the need for a better research classification system that considers what makes science “good” outside of antiquated social class ideologies that have shaped science since ancient Greece. While there are no easy answers to determine what makes research “good,” thinking critically about the types of research projects that will be pursued, and the effects that research has on both science and society, will raise awareness, initiate new conversations, and encourage more dialogue about science in the 21st century.
Differences between basic and applied research were explored through a wet-lab case study. Vaccinia virus (VACV) infections are a prime model of the competition between a virus and its host. VACV contains a gene that is highly evasive of the host immune system, gene E3L. The protein encoded by E3L is E3, which contains two highly conserved regions, a C-terminus, and a N-terminus. While the C-terminus is well-understood, the mechanism by which the N-terminus grants IFN resistance was previously unknown. This project demonstrated that the N-terminus prevents the initiation of programmed necrosis through host-encoded cellular proteins RIP3 and DAI. These findings provide insight into the function of the N-terminus of E3, as well as the unique functions of induced programmed necrosis.
This project was an example of “basic” research. However, it highlights the interconnectivity of basic and applied research and the danger in isolating both projects and perspectives. It points to the difficult decisions that must be made in science, and the need for a better research classification system that considers what makes science “good” outside of antiquated social class ideologies that have shaped science since ancient Greece. While there are no easy answers to determine what makes research “good,” thinking critically about the types of research projects that will be pursued, and the effects that research has on both science and society, will raise awareness, initiate new conversations, and encourage more dialogue about science in the 21st century.
ContributorsSnyder, Caroline Jane (Author) / Jacobs, Bertram (Thesis director) / Hurlbut, Ben (Committee member) / Mateusz, Szczerba (Committee member) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2016-12
Description
Predatory bacteria are a guild of heterotrophs that feed directly on other living bacteria. They belong to several bacterial lineages that evolved this mode of life independently and occur in many microbiomes and environments. Current knowledge of predatory bacteria is based on culture studies and simple detection in natural systems. The ecological consequences of their activity, unlike those of other populational loss factors like viral infection or grazing by protists, are yet to be assessed. During large-scale cultivation of biological soil crusts intended for arid soil rehabilitation, episodes of catastrophic failure were observed in cyanobacterial growth that could be ascribed to the action of an unknown predatory bacterium using bioassays. This predatory bacterium was also present in natural biocrust communities, where it formed clearings (plaques) up to 9 cm in diameter that were visible to the naked eye. Enrichment cultivation and purification by cell-sorting were used to obtain co-cultures of the predator with its cyanobacterial prey, as well as to identify and characterize it genomically, physiologically and ultrastructurally. A Bacteroidetes bacterium, unrelated to any known isolate at the family level, it is endobiotic, non-motile, obligately predatory, displays a complex life cycle and very unusual ultrastructure. Extracellular propagules are small (0.8-1.0 µm) Gram-negative cocci with internal two-membrane-bound compartmentalization. These gain entry to the prey likely using a suite of hydrolytic enzymes, localizing to the cyanobacterial cytoplasm, where growth begins into non-compartmentalized pseudofilaments that undergo secretion of vesicles and simultaneous multiple division to yield new propagules. I formally describe it as Candidatus Cyanoraptor togatus, hereafter Cyanoraptor. Its prey range is restricted to biocrust-forming, filamentous, non-heterocystous, gliding, bundle-making cyanobacteria. Molecular meta-analyses showed its worldwide distribution in biocrusts. Biogeochemical analyses of Cyanoraptor plaques revealed that it causes a complete loss of primary productivity, and significant decreases in other biocrusts properties such as water-retention and dust-trapping capacity. Extensive field surveys in the US Southwest revealed its ubiquity and its dispersal-limited, aggregated spatial distribution and incidence. Overall, its activity reduces biocrust productivity by 10% at the ecosystem scale. My research points to predatory bacteria as a significant, but overlooked, ecological force in shaping soil microbiomes.
ContributorsBethany Rakes, Julie Ann (Author) / Garcia-Pichel, Ferran (Thesis advisor) / Gile, Gillian (Committee member) / Cao, Huansheng (Committee member) / Jacobs, Bertram (Committee member) / Arizona State University (Publisher)
Created2022
Description
Male reproductive dysfunction accounts for almost half of male infertility cases, yet the signaling mechanisms involved in the male reproductive system remain unclear. Although the exact cause of male reproductive dysfunction varies, obtaining a better understanding of the modulators of smooth muscle contractions may provide new targets for the treatment of male reproductive conditions. The male reproductive tract, consisting of the testes, epididymis, vas deferens, and penis, is lined with innervated smooth muscle fibers that transport spermatozoa through the system. Contractions of these smooth muscle fibers can be modulated by neurotransmitters and hormones, like dopamine and norepinephrine, as well as biogenic amines. The focus of this study is on the biogenic amine tyramine, which is produced by the breakdown of tyrosine via decarboxylation. Tyramine has been shown to modulate vasoconstriction and increase blood pressure due to its effect on smooth muscle contractions. This study has found that tyramine localizes in male reproductive tissues and modulates smooth muscle contractions. Age and environment were also found to play a significant role in the expression of tyramine and its associated receptor, TAAR1.
ContributorsSteadman, Solange (Author) / Baluch, Debra (Thesis advisor) / Roberson, Robert (Committee member) / Sweazea, Karen (Committee member) / Arizona State University (Publisher)
Created2023
Description
Access to testing for the human immunodeficiency virus (HIV), as well as other care services related to HIV/AIDS, have greatly improved in Tanzania over the last decade. Despite the country’s efforts to increase the number of individuals who get tested for HIV annually, it is estimated that only 52.2-70.0% of people living with HIV (PLWH) knew their HIV positive status at the end of 2017. In addition, research in Tanzania has shown that HIV-related stigma and discrimination are widespread and contribute to low uptake of HIV testing and non-adherence to antiretroviral treatment (ART). In order to achieve the goals set forth by the Government of Tanzania and the Joint United Nations Programme on HIV/AIDS (UNAIDS), as well as move towards an AIDS-free generation, a deeper understanding of the stigma-related barriers to seeking an HIV test is necessary. This research aims to better understand the relationship between HIV-related stigma and attitudes towards HIV testing among community members in Northern Tanzania. In addition, it looked at the specific barriers that contribute to low uptake of HIV testing, as well as the impact of social networks on an individual’s motivation and willingness to get tested for HIV. In this research, community members in Meru District (N = 108, male = 69.4%, female = 28.7%) were surveyed using various validated instruments that covered a range of topics, including knowledge of HIV/AIDS, testing attitudes, and perceived risk of HIV infection. The mean overall score for correct answers on the knowledge measure was 69.8% (SD = 16.4). There were no significant group differences between individuals who had ever tested and individuals who had not tested in relation to HIV/AIDS knowledge or HIV testing attitudes. The factors that were significantly associated with getting an HIV test were knowing someone who had previously tested (p = 0.003), as well as openly discussing HIV testing within one’s social group (p = 0.017). Participants also provided qualitative responses for barriers to receiving an HIV test, motivations for getting tested, and suggested interventions for improving HIV testing uptake. The goal of this research is to develop recommendations for interventions that are better informed by attitudes and motivations for testing.
ContributorsAllen, Megan (Author) / Jacobs, Bertram (Thesis advisor) / Neuberg, Steven (Committee member) / Ellison, Karin (Committee member) / Arizona State University (Publisher)
Created2019
Description
The advent of new high throughput technology allows for increasingly detailed characterization of the immune system in healthy, disease, and age states. The immune system is composed of two main branches: the innate and adaptive immune system, though the border between these two states is appearing less distinct. The adaptive immune system is further split into two main categories: humoral and cellular immunity. The humoral immune response produces antibodies against specific targets, and these antibodies can be used to learn about disease and normal states. In this document, I use antibodies to characterize the immune system in two ways: 1. I determine the Antibody Status (AbStat) from the data collected from applying sera to an array of non-natural sequence peptides, and demonstrate that this AbStat measure can distinguish between disease, normal, and aged samples as well as produce a single AbStat number for each sample; 2. I search for antigens for use in a cancer vaccine, and this search results in several candidates as well as a new hypothesis. Antibodies provide us with a powerful tool for characterizing the immune system, and this natural tool combined with emerging technologies allows us to learn more about healthy and disease states.
ContributorsWhittemore, Kurt (Author) / Sykes, Kathryn (Thesis advisor) / Johnston, Stephen A. (Committee member) / Jacobs, Bertram (Committee member) / Stafford, Phillip (Committee member) / Stout, Valerie (Committee member) / Arizona State University (Publisher)
Created2014
Description
This study aims to unearth monological and monocultural discourses buried under the power of the dominant biomedical model governing the HIV/AIDS debate. The study responds to an apparent consensus, rooted in Western biomedicine and its "standardizations of knowledge," in the production of the current HIV/AIDS discourse, especially in Sub-Saharan Africa. As a result, biomedicine has become the dominant actor (in) writing and rewriting discourse for the masses while marginalizing other forms of medical knowledge. Specifically, in its development, the Western biomedical model has arguably isolated the disease from its human host and the social experiences that facilitate the disease's transmission, placing it in the realm of laboratories and scientific experts and giving full ownership to Western medical discourse. Coupled with Western assumptions about African culture that reproduce a one-sided discourse informing the social construction of HIV/AIDS in Africa, this Western monopoly thus constrained the extent and efficacy of international prevention efforts. In this context, the goal for this study is not to demonize the West and biomedicine in general. Rather, this study seeks an alternative and less monolithic understanding currently absent in scientific discourses of HIV/AIDS that frequently elevates Western biomedicine over indigenous medicine; the Western expert over the local. The study takes into account the local voices of Sub-Saharan Africa and how the system has affected them, this study utilizes a Foucauldian approach to analyze discourse as a way to explore how certain ways of knowledge are formed in relation to power. This study also examines how certain knowlege is maintaned and reinforced within specific discourses.
ContributorsAbdalla, Mohamed (Author) / Jacobs, Bertram (Thesis advisor) / Robert, Jason (Committee member) / Klimek, Barbara (Committee member) / Arizona State University (Publisher)
Created2014
Description
The intracellular motility seen in the cytoplasm of angiosperm plant pollen tubes is known as reverse fountain cytoplasmic streaming (i.e., cyclosis). This effect occurs when organelles move anterograde along the cortex of the cell and retrograde down the center of the cell. The result is a displacement of cytoplasmic volume causing a cyclic motion of organelles and bulk liquid. Visually, the organelles appear to be traveling in a backwards fountain hence the name. The use of light microscopy bioimaging in this study has documented reverse fountain cytoplasmic streaming for the first time in fungal hyphae of Rhizopus oryzae and other members in the order Mucorales (Mucoromycota). This is a unique characteristic of the mucoralean fungi, with other fungal phyla (e.g., Ascomycota, Basidiomycota) exhibiting unidirectional cytoplasmic behavior that lacks rhythmic streaming (i.e., sleeve-like streaming). The mechanism of reverse fountain cytoplasmic streaming in filamentous fungi is currently unknown. However, in angiosperm plant pollen tubes it’s correlated with the arrangement and activity of the actin cytoskeleton. Thus, the current work assumes that filamentous actin and associated proteins are directly involved with the cytoplasmic behavior in Mucorales hyphae. From an evolutionary perspective, fungi in the Mucorales may have developed reverse fountain cytoplasmic streaming as a method to transport various organelles over long and short distances. In addition, the mechanism is likely to facilitate driving of polarized hyphal growth.
ContributorsShange, Phakade Mdima (Author) / Roberson, Robert W. (Thesis advisor) / Gile, Gillian (Committee member) / Baluch, Debra (Committee member) / Arizona State University (Publisher)
Created2020
Description
Prior to the first successful allogeneic organ transplantation in 1954, virtually every attempt at transplanting organs in humans had resulted in death, and understanding the role of the immune mechanisms that induced graft rejection served as one of the biggest obstacles impeding its success. While the eventual achievement of organ transplantation is touted as one of the most important success stories in modern medicine, there still remains a physiological need for immunosuppression in order to make organ transplantation work. One such solution in the field of experimental regenerative medicine is interspecies blastocyst complementation, a means of growing patient-specific human organs within animals. To address the progression of immune-related constraints on organ transplantation, the first part of this thesis contains a historical analysis tracing early transplant motivations and the events that led to the discoveries broadly related to tolerance, rejection, and compatibility. Despite the advancement of those concepts over time, this early history shows that immunosuppression was one of the earliest limiting barriers to successful organ transplantation, and remains one of the most significant technical challenges. Then, the second part of this thesis determines the extent at which interspecies blastocyst complementation could satisfy modern technical limitations of organ transplantation. Demonstrated in 2010, this process involves using human progenitor cells derived from induced pluripotent stem cells (iPSCs) to manipulate an animal blastocyst genetically modified to lack one or more functional genes responsible for the development of the intended organ. Instead of directly modulating the immune response, the use of iPSCs with interspecies blastocyst complementation could theoretically eliminate the need for immunosuppression entirely based on the establishment of tolerance and elimination of rejection, while also satisfying the logistical demands imposed by the national organ shortage. Although the technology will require some further refinement, it remains a promising solution to eliminate the requirement of immunosuppression after an organ transplant.
ContributorsDarby, Alexis Renee (Author) / Maienschein, Jane (Thesis advisor) / Robert, Jason (Thesis advisor) / Ellison, Karin (Committee member) / Arizona State University (Publisher)
Created2020
Description
This thesis reviews the initial cases of fetal surgery to correct myelomeningocele, a severe form of spina bifida, and discusses the human and social dimensions of the procedure. Myelomeningocele is a fetal anomaly that forms from improper closure of the spinal cord and the tissues that surround it. Physicians perform fetal surgery on a developing fetus, while it is in the womb, to mitigate its impacts. Fetal surgery to correct this condition was first performed experimentally in the mid-1990and as of 2020, it is commonly performed. The initial cases illuminated important human and social dimensions of the technique, including physical risks, psychological dimensions, physician bias, and religious convictions, which affect decision-making concerning this fetal surgery. Enduring questions remain in 2020. The driving question for this thesis is: given those human and social dimensions that surround fetal surgery to correct myelomeningocele, whether and when is the surgery justified? This thesis shows that more research is needed to answer or clarify this question.
ContributorsEllis, Brianna (Author) / Maienschein, Jane (Thesis advisor) / Ellison, Karin (Thesis advisor) / Robert, Jason (Committee member) / Arizona State University (Publisher)
Created2020