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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

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
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Cervical cancer, which many physicians of 2019 consider to be a success in terms of establishing widely used forms of early preventative and diagnostic technologies, experienced a reduction in incidence rates in women by over fifty percent between 1975 and 2016. Cervical cancer does not often present in women with

Cervical cancer, which many physicians of 2019 consider to be a success in terms of establishing widely used forms of early preventative and diagnostic technologies, experienced a reduction in incidence rates in women by over fifty percent between 1975 and 2016. Cervical cancer does not often present in women with symptoms until it has entered a later stage of the disease. Because of this fact, in the early twentieth century, physicians were often only able to diagnose cervical cancer when either the woman reported complaints or there was a visual confirmation of lesions on the cervix. The symptoms women often reported included vague abdominal pain, bleeding after sex, and abnormal amounts of vaginal discharge, all of which are non-specific symptoms, making it even harder for women to be diagnosed with cervical cancer. This thesis answers the following question: How does the history of cervical cancer show that prevention helps reduce rates of cancer-related deaths among women? By studying the history of cervical cancer, people can understand how a cancer that was once one of the top killers of women in the US has declined to become one of the lowest through the establishment of and effective communication of early prevention and diagnostics, both among the general public and within the medical community itself. This thesis is organized based on key episodes which were pertinent to the history of cervical cancer, primarily within the United States and Europe. The episodes are organized in context of the shifts in thought regarding cervical cancer and include topics such as vaccine technologies like the Gardasil and Cervarix vaccines, social awareness movements that educated women on the importance of early detection, and analyses of the early preventative strategies and attempts at treating cervical cancer. After analyzing eleven key episodes, the thesis determined that, through the narrative of early attempts to treat cervical cancer, shifting the societal thought on cancer, evolving the importance of early detection, and, finally, obtaining a means of prevention, the history of cervical cancer does demonstrate that the development of preventative strategies has resulted in reducing cancer-related deaths among women. Understanding what it took for physicians to evolve from simply detecting cervical cancer to being able to prevent it entirely matters because it can change the way we think about managing other forms of cancer.
ContributorsDarby, Alexis Renee (Co-author) / Darby, Alexis (Co-author) / Maienschein, Jane (Thesis director) / Abboud, Carolina (Committee member) / Ellison, Karin (Committee member) / School of Life Sciences (Contributor, Contributor, Contributor) / Barrett, The Honors College (Contributor)
Created2019-05