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

克里斯平·巴克的博士论文提供了我们目前对衰老的分子理解是如何在20世纪40年代至90年代从冷战辐射实验到今天的端粒理论发展的第一次历史。这项博士论文研究改进基金申请了访问美国六个档案馆的资金。每一次访问的目的都是分析每个档案馆特有的文件，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·麦克林托克的案例中，影响了人们对衰老的思考)。这六个档案馆是：原子弹伤亡委员会的记录(华盛顿特区)；原子能委员会的核试验档案(拉斯维加斯，新泽西州)；利奥·西拉德文件(拉霍亚，C.A.)；莱斯利·奥格尔文件(拉霍亚，C.A.)；H.J.穆勒手稿集(布卢明顿，伊利诺伊州)；芭芭拉·麦克林托克文件(费城，P.A.)。已经获得了访问每个档案和使用所需文件的许可。智力价值：这项研究的智力价值有三个方面。首先，它将使协作组完成论文。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储存库收藏中被忽视的重要部分的认识。第三，克里斯平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。这位合作者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熟练程度。广泛影响：这篇论文从三个方面极大地促进了科学史上的学术研究。首先，它使老年学的历史跨越了1930年。在分子生物学被确立为一个科学领域之前，历史学家们关于老年学发展的先前工作就停止了。克里斯平的论文将把老年学的历史扩展到辐射生物学、DNA和分子遗传学时期，并将开启二战后老龄化时代的研究。这篇论文为分子生物学的历史增添了一个重要的篇章。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；它被发现DNA的戏剧性事件所掩盖。只有一位学者在研究这一主题，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在这个关键时刻的实验和理论的影响，将改变我们对现代生物学发展的理解。第三，本论文首次对生物学的一个子领域的分子化进行了深入研究。在分子生物学建立后，老年学和癌症等专业领域成为分子科学。很少有人注意到生物学中的子领域如何采用分子范式，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，Co-Pi将为科学史学家提供一种关于生物学和医学的分子化的新思维方式。

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 Second, it uses historical documents that have never been studied.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