spacer
Chancellor's Distinguished Dissertation Award

Chancellor’s Distinguished Dissertation Award

 

First Place

Jonathan S. Jones, Department of History, Binghamton University
"Opium Slavery: Veterans and Addiction in the American Civil War Era"

"[E]legantly written, cogently argued, and prodigiously research piece of original and important scholarship that will have significant reverberations in the field of US history and in the public realm as well" … "a tour de force"  -- Diane Miller Sommerville, President , Southern Association for Women Historians

"[I]t’s hard to find something original on the American Civil War. There are tens of thousands of books on it; finding daylight is a near impossible task. Jonathan has not only done that, he’s found something hiding in plain sight: how the medical community treated hurt soldiers with opium, and the consequences of what happened when many of them became addicts in the postwar years." – Robert Parkinson, Associate Professor, History, Binghamton University

"[D]eeply researched, beautifully written, and strikingly original study of the post-Civil War opium crisis that promises to have wide influence." – Judith Giesberg, Robert M. Birmingham Chair in the Humanities, Professor, Department of History, Villanova University

Abstract:

Albert Henley, a broken-down Civil War veteran, made an agonizing confession in 1878. "In the army," he explained, "I had to use opiates for a complication of painful diseases." Addictive morphine soon "fastened its iron grip on my very vitals and held me enchained and enslaved" for decades after leaving the military. In the U.S. Civil War’s wake, tens of thousands of veterans like Henley became addicted to prescription opium and morphine, medicines used to treat painful amputations, lingering sicknesses, depression, and other war-related ailments. Families, doctors, and government officials looked on in horror as "slavery" to opium and morphine destroyed veterans’ health and reputations, undermined their manhood and whiteness, imperiled access to military pensions, and culminated in institutionalization, jail, or grisly overdose deaths. As this Civil War-era opiate addiction epidemic—America’s first opioid crisis—unfolded during the late-nineteenth and early-twentieth centuries, drug addiction caused tremendous suffering for veterans, alarmed the public and state, and rattled the foundations of American medicine. This dissertation is the first major study of opiate addiction among Civil War veterans, one of the least investigated health and social aftershocks of America’s most destructive war. For a century, historians have been vaguely aware that Civil War survivors sometimes became addicted to drugs. Yet until now, amidst the U.S.’s twenty-first-century opioid crisis, the post-Civil War opiate epidemic has been relegated to the footnotes of history books. Scholars have overlooked the massive scale of prescription drug addiction after the Civil War, the myriad and pernicious effects of "opium slavery" on veterans’ lives, as well the crisis’s transformative effects on the development of American medicine and U.S. drug policy. This study reconstructs the causes and consequences of opiate addiction among Civil War veterans, utilizing rare, largely untapped medical records from late-nineteenth-century hospitals and mental asylums in conjunction with newly accessible Civil War-era medical journals, newspapers, and military records. The traumatic lived experiences and negative outcomes of addiction for veterans and their families are foregrounded; in doing so, this dissertation illuminates the unexpected medical legacies of the Civil War, significantly enhancing historians’ understandings of the intersecting, long-term health and social crises arising from the war. This study also calls into question major narratives in the history of American medicine, illuminating the U.S.’s long, but largely forgotten, nineteenth-century history of opioid crises

Additional Information:

Mr. Jones has already published five scholarly, single-author, peer-reviewed articles on this topic as well as more than ten articles on opiate addiction in a historical context for venues such as the Washington Post, Vice, Gotham, Slate, The Civil War Monitor, and Nursing Clio. His article for The Conversation on the history of pharmaceutical fraud has been republished in the Chicago Tribune, the Houston Chronicle and more than 12 other outlets.

He has been interviewed by C-Span’s American History TV; the Rogue Historian and the History Hack podcasts; WBUR-Boston’s Common Health show, and West Virginia Public Media.

Mr. Jones’s research has been supported by grants and fellowships from the following: the George and Ann Richards Civil War Era Center at Pennsylvania State University; the Kentucky Historical Society; the William and Mary Libraries; the Harvey Cushing/John Hay Whitney Medical Library at Yale University; the Virginia Historical Society in conjunction with the Andrew W. Mellon Foundation; the New York Historical Society; the North Carolinian Society; the Louis Round Wilson Special Collections Library at University of North Carolina, Chapel Hill; the Duke University Rubenstein Rare Book and Manuscript Library; the New York State Archives; the Huntington Library; the Consortium for History of Science, Technology and Medicine; and the College of Physicians of Philadelphia.

 

Finalists

Several fundamental cellular processes rely on the assembly, disassembly, and dynamics of the cell’s structural cytoskeleton. Actin, a monomeric protein, forms filaments in the cell composing a main component of the cytoskeleton. The spatial and temporal regulation of actin filament nucleation and assembly ensures these filaments form at the right time and place to provide the force needed to carry out functions including cell division, cell motility, and endocytosis, or the intake of extracellular materials. One regulator of actin filament assembly is the Arp2/3 complex, which nucleates dense branched actin networks. The Arp2/3 complex exists in an inactive form until bound by a class of activator proteins known as Nucleation Promoting Factors (NPFs). One NPF is the Wiskott-Aldrich Syndrome protein, or WASp. Patients with mutations in the gene encoding WASp can develop serious diseases including multiple cancers and the eponymous immune disorder Wiskott-Aldrich Syndrome. WASp interacts with several proteins including WIP, or WASp Interacting Protein. In animals, WASp protein is degraded if the WIP-WASp interaction is disrupted, making it difficult to understand the individual contributions of these proteins in living cells. However, in yeast WASp remains stably expressed in the absence of WIP, providing an ideal environment to study mechanisms of WASp regulation. Importantly, how WASp proteins are regulated at sites of endocytosis remains unclear. In this collection of studies, we used a combination of yeast genetics and quantitative live cell microscopy to better understand the mechanisms of actin assembly at sites of endocytosis. In Chapter 2, we observed WASp and WIP form a transient complex with the motor protein Myosin-1 near the membrane, orienting branched actin filaments in a position to optimize force generation. In Chapter 3, we dissected the individual contributions of WIP fragments in actin assembly and discovered that the WIP-WASp interaction is essential for WASp-mediated branched actin assembly. In Chapter 4, we examined how a separate module of endocytic proteins contributes to actin assembly and discovered the protein Sla1 inhibits WASp NPF activity after the endocytic vesicle begins to internalize. In Chapter 5, we examined how WASp and Myosin-1 impact additional endocytic modules and discovered WASp plays an important role in expediating endocytosis and Myosin-1 contributes to the localization of several proteins. Lastly, in Chapter 6, we observed that blocking the fast-growing end of actin filaments does not impact actin assembly at sites of endocytosis. Together these studies provide key, novel insights into how actin assembly is regulated to efficiently carry out essential processes in living cells.

 

The National Spinal Cord Injury (SCI) Center estimates over 300,000 individuals living with SCI, nearly 18,000 new cases per year, and ~1,100 of those living in New York State. SCI translational research has been a priority of the NYS Department of Health (DOH) Spinal Cord Injury Research Board (SCIRB) for over two decades due to lifelong physical and mental health hardships for patients and their families as well as the substantial medical and economic costs. SCI is an abrupt, traumatic event that injures the central and peripheral nervous system (CNS, PNS) connections in the spine, contusing or severing spinal neuron axons and damaging support cells. Neurons in the spine are non-regenerating if lost. Injuries therefore lead to incurable motor and sensory deficits that can affect motion, and can also impact all organ systems in the body. It is a devastating, life-changing event that requires innovative, transformative solutions. Stem cell research is revolutionizing therapies for human nervous system function, dysfunction, and repair. Currently there exists no other comprehensive cell therapeutic strategy to address restored neural connectivity of target tissues or to unlock regeneration to restore function. Transplantable neurons and neuronal networks require custom matching of neural cells to the patient injury site to enhance functional re-innervation. NYS DOH programs have further enabled groundbreaking solutions in this work by funding challenging, transformative initiatives with attention to broader impacts on population diversity. For example, the totality of this SCIRB-funded research was performed using ethnically-diverse human induced pluripotent stem cell lines of African American, Hispanic Latino, and Asian self-proclaimed individuals generated previously in the Paluh laboratory as a NYSTEMfunded project. These lines are the first of their kind in stem cell research and bring increased representation of the diverse NYS population to stem cell-based SCI therapeutic advancements. By advancing human neural stem cell technologies, including CNS-PNS in vitro models and transplantable spinal neural circuits, my contributions are enabling the next-generation of SCI treatments. The ability to observe fundamental processes that direct delivery of the appropriate nerve supply is essential for restoring lost function at any stage after injury. As such, I developed an in vitro model of human neuronal innervation coupled to organogenesis of other tissues such as the developing heart and gastrointestinal tract to study how new neurons come to innervate non-neural organ systems that are also affected by SCI. The impact of my dissertation research is reflected in six top tier first-author publications that include Nature Communications and iScience, Cell Reports in review, an invited talk at the Society for Neuroscience international conference, and patents pending. As an M.D./Ph.D. student in the combined degree program between SUNY Polytechnic Institute and SUNY Downstate Medical Center in Nanomedicine and Nanoscale Engineering, my Ph.D. research provides an excellent foundation for continuing my M.D. degree and to pursue my interests in neurosurgery as a physician-scientist. Together, this work epitomizes the strengths of the NYS education system and programs that support the highest caliber innovations for impactful advances in biomedicine.

 

College presents a unique environment for exploring, defining, and refining key developmental assets, like one’s senses of identity and self-direction. Although rich with opportunities for self-discovery, college is also rich with opportunities for risk: the transition to and through college is stressful, often associated with the onset or exacerbation of mental illness. Recent large-scale observational studies have estimated that some types of psychiatric distress—like depression and suicide-related thoughts and behaviors—have nearly doubled among American college students in the last decade. This underscores the need to better understand how the college transition, and the developmental processes often occurring within it, are related to well-being. This study followed 579 students from freshman to senior year of college to examine how derailment, or difficulties reconciling perceived identity change resulting in the sense one is "off-course" in life, relates to downstream depressive symptoms. Although significantly and positively related to one another at concurrent observations, there was insufficient evidence to suggest that derailment in freshman year meaningfully predicted levels of depressive symptoms in senior year on average. Notably, however, trait self-reflection in freshman year (i.e., the propensity to think about the self and one’s experiences in an emotionallydistanced and analytic way) moderated this association: freshman derailment was a positive predictor of senior depression among only those with the lowest tendencies toward self-reflection. Among those highest in trait self-reflection, the association between freshman derailment and senior depression trended negatively. In the first observation of its kind, univariate latent growth curve modeling suggested that derailment tended to increase linearly from freshman to senior year, and depressive symptoms were characterized by a significant uptick in distress across the first semester of college that appeared to persist through the end of senior year. Exploratory qualitative analyses, aided by a machine learning tool for text analysis known as Latent Dirichlet Allocation, were also conducted to provide the field with its first topographical understanding of derailment. This led to the discovery of five themes associated with students’ derailment experiences that may have implications for the way derailment interfaces with mental health: Insight into Personal Changes (e.g., progression, regression, and stability), Overcoming Challenges (e.g., growing as a result of hardship), Evaluating Clarity of Direction (e.g., optimism, confidence, certainty, or anxiety surrounding one’s path or lack thereof), Contending with Major Turbulence (e.g., mental illness, death, poverty), and The Path (e.g., objective reports of changes in career trajectory). Together, these findings suggest that enhancing students’ ability to self-reflect effectively may be a promising target for alleviating distress associated with perceived derailment. This study also suggests that derailment is a salient experience for college students, reported at greater levels as students prepare for the transition out of college, and experienced in a variety of ways. Experimental follow-up of these findings is incumbent, and tailoring future interventions for college seniors may be particularly worthwhile. With derailment representing a novel psychological construct that synthesizes developmental, social, and clinical fields, these findings are well-positioned to inform efforts aimed at promoting healthy transitions to adulthood.

 

Estrogens are known to play an important role in regulation of a myriad of central nervous system (CNS) functions. These include mood, memory, cognition, neuroprotection, and nociception. Estrogen receptors (ERs) and aromatase (aka estrogen synthase) are present not only in reproductive organs, but are also found throughout the CNS. Factors regulating CNS aromatase activity (and thus the availability of locally produced estrogens) are largely unexplored, as are the sources of estrogens impacting CNS functionalities. Our laboratory recently demonstrated that both aromatase and at least one type of ER, ERα, oligomerizes with aromatase. Furthermore, both ERα and aromatase are present within a multimeric membrane signaling unit. We coined the term ‘oligocrine’ to describe the estrogenic signaling that occurs within the same complex in which the estrogens are produced. This novel form of estrogenic signaling complements the more traditional endocrine relationship between aromatase and ERs. In this project, I investigated the organizational relationship of CNS aromatase and membrane ERα (mERα), a rapid signaling plasma membrane ER, using coimmunoprecipitation and Western blot analyses. I also explored the regulation of aromatase activity in spinal cord and hypothalamus using the tritiated water release activity assay and the phosphorylation state of the enzyme. I concluded that (1) aromatase and mERα coexist in a membrane complex in two functionally distinct regions of the CNS: spinal cord (predominantly neural) and hypothalamus (neuroendocrine), (2) in spinal cord, aromatase is organized to signal nearly exclusively in oligocrine fashion, whereas in hypothalamus, aromatase is organized to predominantly produce estrogens for export, (3) spinal aromatase activity can be inversely related to circulating estrogen levels, and (4) CNS aromatase activity can be acutely modulated by phosphorylation, independent of genomic regulation. My studies revealed a remarkable complexity of CNS estrogenic signaling. Results offer a glimpse into how CNS estrogenic signaling is segregated on subcellular as well as regional levels in a functionality-dependent manner. Observations could also explain how some estrogen-dependent CNS functionalities peak in-phase, while others peak out-ofphase with circulating estrogens, underscoring the imperative to include not only sex, but also stage of menstrual cycle as a biological variable when designing clinical trials targeting estrogen-dependent CNS functionalities. Finally, developing therapeutic approaches that target specific subcellular populations of aromatase and ERα could selectively facilitate restoration of impaired estrogen-dependent CNS functionalities while limiting undesirable effects

 

Honorable Mentions