The Development of Plant Virology in the Early 20th Century

在世纪早期，随着细菌和真菌的发现，一个主要的问题是确定病毒的“性质”，特别是烟草花叶病毒（TMV）。对病毒特性的研究具有基本的科学意义和实用价值。TMV作为烟草、番茄和辣椒的重要农业病害，在20世纪30年代中期也成为发现病毒结构和物理化学的模式系统。这项研究的目的是调查1900年至1940年植物病毒学中未被探索的事件，这些事件促进了植物病理学的专业化以及专注于农业和植物病毒学的机构的发展。在世纪早期，植物病原体TMV从田间转移到实验室，导致了对病毒性质的发现和新技术的发展，这些技术今天仍然作为植物分子生物学，结构生物学和植物育种的常用工具的集合。为了理解这些工具和概念的发展和完善，我建议从20世纪初美国的TMV工作开始，直到Stanley在1935年发现TMV可以被结晶化，为“新生物学”和推动病毒的生物化学和分子表征奠定了基础。弗朗西斯O. Holmes在TMV成为病毒结构和分子生物学的理想工具方面发挥了重要作用。霍姆斯是博伊斯汤普森植物研究所（1924-1932）和洛克菲勒医学研究所（1932-1960）的成员。从1929年到1936年，Holmes的特别发现是i）抗性基因N可以在植物物种之间转移，ii）具有N基因的植物可以用于确定病毒滴度和运动，iii）该基因可以部署在作物植物中以防止田间TMV感染。然而，这些知识是如何演变的，在很大程度上是未知的。我有兴趣确定这项研究是如何发展的，以及谁是发现和早期使用今天被认为是司空见惯的工具的主要参与者。这项研究的独特之处在于专注于农业和实验室研究的交叉点。这些与TMV有关的观察结果，既是基础生物学的工具，以了解宿主植物抗性的遗传学，TMV的遗传学，也是实际应用的工具，包括Stanley用来监测他的分离TMV的纯化/感染性方案的成功。植物育种家通过改良番茄、烟草和胡椒等经济上重要的高价值经济作物而受益。在他的职业生涯中，霍姆斯确定并研究了植物病毒学的核心问题（今天分子植物病毒学家仍然非常感兴趣的问题），包括病毒如何在植物中传播以及宿主植物对TMV抗性的遗传机制。我的特别兴趣和目标的拟议研究是早期的工作与TMV。一个目的是调查的发展和完善的局部病变检测，以产生纯培养的TMV，准确地确定病毒滴度和突变体的特点。另一个目的是调查的认识，局部病变测定实际上是一种抗性反应，烟草中的特定基因可以渗入到经济上重要的植物，以消除烟草花叶病的破坏性影响。第三个目标是调查导致向抗TMV作物过渡的事件。更广泛的影响。与过去一样，来自不同背景的本科生将被招募并参与研究。研究结果将在专业会议和期刊文章中向科学史学家和科学界传播。此外，几个推广场所计划包括一个新的本科课程，一个网页，数据库，开放存取和同行评审的网络练习和教程，并将调查结果纳入本科生和研究生的实验室练习TMV。

In the early 20th century, a primary question, following the discovery of bacteria and fungi, was to determine the "nature" of a virus-in particular, Tobacco mosaic virus (TMV). The study of the properties of viruses was of basic scientific interest and of practical value. TMV, as an agriculturally important disease of tobacco, tomato, and peppers, also became a model system in the discovery of the structure and physicochemistry of viruses the mid-1930s. The purpose of this proposed research is to investigate unexplored events in plant virology from 1900 to 1940 that paralleled the professionalization of plant pathology and the development of institutions focused on agriculture and plant virology. In the early 20th century, the plant pathogen TMV made the transition out of the field and into the lab, resulting in discoveries about the nature of the virus and the development of new technology that remains in place today as a collection of common tools for plant molecular biology, structural biology, and plant breeding. For the purposes of understanding the development and refinement of these tools and concepts, I propose to begin with the TMV work in the United States in the early twentieth century until Stanley's discovery in 1935 that TMV could be crystallized-setting the stage for the 'new biology' and the push for biochemical and molecular characterization of viruses. Two seminal findings by Francis O. Holmes played an essential role in TMV becoming an ideal tool for structural and molecular biology of viruses. Holmes was a member of the Boyce Thompson Institute for Plant Research (1924-1932) and the Rockefeller Institute for Medical Research (1932-1960). From 1929-1936, Holmes' particular discoveries were i) that a resistance gene N could be transferred between plant species, ii) that plants with the N gene could be used to determine virus titer and movement, and iii) this gene could be deployed in crop plants to prevent TMV infections in the field. However, how this knowledge evolved is largely unknown. I am interested in determining how this research was developed and who were the primary actors in the discovery and early use of tools that are considered commonplace today.Intellectual Merit. The unique aspect of this research is the focus on the intersection of agriculture and laboratory research. These observations, related to TMV, were both tools for basic biology to understand the genetics of host-plant resistance, the genetics of TMV, and practical applications including those used by Stanley to monitor the success of his purification/infectivity schemes to isolate TMV. Plant breeders benefited by improving economically important, high-value cash crops such as tomato, tobacco, and pepper. During his career Holmes identified and worked on questions central to plant virology (questions that remain of great interest to molecular plant virologists today), including how viruses spread in the plant and the genetic mechanisms of host-plant resistance to TMV. My particular interests and objectives for the proposed research are the early work with TMV. One objective is to investigate the development and refinement of the local lesion assay to produce pure cultures of TMV, accurately determine virus titer and to characterize mutants. Another objective is to investigate the realization that the local lesion assay was in fact a resistance response and that a particular gene in tobacco could be introgressed into economically important plants to abrogate the devastating effects of tobacco mosaic disease. A third objective is to investigate the events that culminated in the transition towards TMV-resistant crop plants. Broader Impact. As in the past, undergraduate students from diverse backgrounds will be recruited and involved in research. The results will be disseminated both to historians of science and the scientific community at professional meeting and in journal articles. In addition, several outreach venues are planned to include a new undergraduate course, a web page, database, open access and peer reviewed web exercises and tutorials, and integrate the findings into undergraduate and graduate laboratory exercises on TMV.