Dissertation Research: From "terminal gene" to "time bomb": Telomeres, Aging, and Cancer in the Era of Molecular Biology

论文研究：从“末端基因”到“定时炸弹”：分子生物学时代的端粒、衰老与癌症

• 批准号: 0522567
• 负责人: Daniel Kevles
• 金额: --
• 依托单位: Yale University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-08-01 至 2009-04-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0522567&HistoricalAwards=false
• 关键词: Dissertation; Research; terminal; gene; time

Crispin Barker's doctoral dissertation provides the first history of how our current, molecular understanding of aging developed between the 1940s and 1990s, from the Cold War radiation experiments to today's telomere theory. This doctoral dissertation research improvement grant requests funds to visit to six archives in the United States. The object of each of these visits is to analyze documents unique to each archive that tell how a specific biologist or federal research commission studied aging (or, in the case of Barbara McClintock, influenced thinking about aging). The six archives are: the records of the Atomic Bomb Casualty Commission (Washington, D.C.); the Nuclear Testing Archive of the Atomic Energy Commission (Las Vegas, N.V.); the Leo Szilard Papers (La Jolla, C.A.); the Leslie Orgel Papers (La Jolla, C.A.); the H.J. Muller Manuscripts Collection (Bloomington, I.N.); and the Barbara McClintock Papers (Philadelphia, P.A.). Permission to visit each archive and use the required documents has been obtained.Intellectual Merit:The intellectual merit of this research is threefold. First, it will enable the Co-PI to complete the dissertation. Second, it uses historical documents that have never been studied. Analysis of those documents will make a significant contribution to the history of gerontology and raise awareness of an important, neglected part of these major repositories' collections. Third, Crispin's research is highly interdisciplinary, reflecting the diversity of the sciences that were applied to the study of aging. The Co-PI has developed the expertise needed to conduct this research, and will further increase his interdisciplinary proficiency by visiting these archives.Broader Impact:This dissertation significantly advances scholarship in the history of science in three ways. First, it moves the history of gerontology past 1930. Previous work by historians on the development of gerontology stops before molecular biology was established as a scientific field. Crispin's dissertation will extend the history of gerontology into the period of radiation biology, DNA, and molecular genetics, and will open the post-World War Two era of aging to research. The dissertation adds a significant chapter to the history of molecular biology. Very little has been done on the influence of military radiation biology on molecular biology in the 1940s and 1950s; it has been overshadowed by the drama of the discovery of DNA. Only one other scholar is working on the topic, and that scholar is also in the first stages of research. Describing the influence of Atomic Bomb Casualty Commission and Atomic Energy Commission experiments and theories at this critical juncture will revise our understanding of the development of modern biology. Third, the dissertation provides one of the first in-depth studies of the molecularization of a sub-field of biology. Specialized areas such as gerontology and cancer became molecular sciences after molecular biology was well established. Little attention has been paid to the ways in which sub-fields within biology adopted the molecular paradigm, and how, in alliance with another sub-field or singly, they subtly influenced the direction of molecular biology as a whole. By making this transformation a central theme of his dissertation, the Co-PI will provide historians of science with a new way of thinking about the molecularization of biology and medicine.

Crispin Barker的博士论文提供了我们当前对衰老的分子理解如何在20世纪40年代至90年代之间发展的第一个历史，从冷战辐射实验到今天的端粒理论。这篇博士论文研究改进补助金要求资金访问美国的六个档案馆。每一次访问的目的都是分析每个档案馆独有的文件，这些文件讲述了特定的生物学家或联邦研究委员会如何研究衰老（或者，在芭芭拉·麦克林托克的情况下，影响了对衰老的思考）。这六份档案是：原子弹爆炸伤亡委员会（华盛顿，华盛顿特区）的记录;原子能委员会核试验档案馆（拉斯维加斯）; Leo Szilard文件（拉霍亚，C.A.）; Leslie Orgel Papers（拉霍亚，C.A.）; H. J. Muller Mandarepts Collection（布卢明顿，I.N.）;和芭芭拉麦克林托克文件（费城，宾夕法尼亚州）。访问每个档案馆和使用所需文件的许可已经获得。智力价值：这项研究的智力价值是三方面的。首先，它将使Co-PI完成论文。其次，它使用了从未被研究过的历史文献。对这些文件的分析将对老年学的历史作出重大贡献，并提高人们对这些主要资料库收藏的一个重要而被忽视的部分的认识。第三，Crispin的研究是高度跨学科的，反映了应用于衰老研究的科学的多样性。共同PI已经开发了进行这项研究所需的专业知识，并将通过访问这些档案进一步提高他的跨学科能力。更广泛的影响：本论文显着推进学术在科学史上的三个方面。首先，它将老年学的历史推到了1930年之后。历史学家之前关于老年学发展的工作在分子生物学被确立为一个科学领域之前就停止了。Crispin的论文将把老年学的历史延伸到辐射生物学、DNA和分子遗传学的时期，并将开启二战后的老龄化研究时代。 本论文为分子生物学史增添了重要的一章。在20世纪40年代和50年代，关于军事辐射生物学对分子生物学的影响，人们做得很少;它被DNA发现的戏剧性所掩盖。只有另外一位学者正在研究这个课题，而且这位学者也处于研究的第一阶段。描述原子弹伤亡委员会和原子能委员会的实验和理论在这一关键时刻的影响，将修正我们对现代生物学发展的理解。第三，本论文提供了一个第一次深入研究的分子生物学的一个子领域。在分子生物学建立之后，老年学和癌症等专门领域成为分子科学。很少有人注意到生物学中的子领域是如何采用分子范式的，以及它们是如何与另一个子领域联合或单独地微妙地影响整个分子生物学的方向的。通过将这种转变作为他论文的中心主题，Co-PI将为科学史家提供一种思考生物学和医学分子化的新方法。