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

Crispin Barker的博士论文首次提供了我们目前对衰老的分子理解是如何在20世纪40年代到90年代之间发展起来的历史，从冷战时期的辐射实验到今天的端粒理论。本博士论文研究改进资助申请经费访问美国六个档案馆。每次访问的目的都是分析每个档案的独特文件，这些文件讲述了特定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案例中，影响了对衰老的思考）。这六份档案是：原子弹伤亡委员会的记录（华盛顿特区）；原子能委员会核试验档案（内华达州拉斯维加斯）；利奥·西拉德文件（La Jolla, ca）；莱斯利·奥格尔论文（La Jolla, ca）；h·j·穆勒手稿收藏（布卢明顿，n.n）；和芭芭拉麦克林托克论文（费城，宾夕法尼亚州）。已获得访问各档案馆和使用所需文件的权限。智力价值：这项研究的智力价值是三重的。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做出重大贡献，并提高人们对这些主要资料库藏品中一个重要的、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。副主任已经发展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：这篇论文在三个方面显著地推进了科学史的学术研究。首先，它将老年学的历史推到了1930年之后。在分子生物学被确立为一门科学领域之前，历史学家对老年学发展的研究就停止了。Crispin的论文将把老年学的历史扩展到辐射生物学、DNA和分子遗传学的时期，并将开启二战后的衰老研究时代。这篇论文为分子生物学的发展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的研究很少；它被DNA发现的戏剧性所掩盖。只有另外一位学者在研究这个课题，而且这位学者也处于研究的初级阶段。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个关键时刻的影响，将改变我们对现代生物学发展的理解。第三，本文首次对生物学分支领域的分子化进行了深入研究。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采用分子范式的方式，以及它们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。通过将这种转变作为他论文的中心主题，他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。

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 Second, it uses historical documents that have never been studied.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.