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病毒发病机制的奥德赛

An Odyssey to Viral Pathogenesis.

机构信息

Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, California 92037; email:

出版信息

Annu Rev Pathol. 2016 May 23;11:1-19. doi: 10.1146/annurev-pathol-012615-044107. Epub 2015 Oct 22.

Abstract

This odyssey is mine from early junior high school, where my dreams for adventure were shaped by Arthur Conan Doyle's Sherlock Holmes, Percival Christopher Wren's Beau Geste, and best of all the remarkable explorers in Paul de Kruif's Microbe Hunters. My birth site was in Manhattan (my mother was a Vogue model and my father worked in retail), and I traveled to college at the University of Alabama, Tuscaloosa, where my love of history and English literature was shaped along with a sufficient exposure to biology, chemistry, and genetics to meet requirements for entering medical school. By the second year at the University of Maryland School of Medicine, through expert teachers such as Theodore (Ted) Woodward and Sheldon (Shelly) Greisman in medicine and Charles Weissmann in virology and microbiology, I found that understanding why and how people became ill was more my cup of tea than identifying and treating their illnesses. Although I was becoming competent in diagnosis and treatment, I left medical school at the end of my sophomore year to seek a more basic understanding of biology and chemistry. I achieved this by working toward a PhD in biochemistry at Johns Hopkins McCollum-Pratt Institute combined with study of rickettsial toxin at Maryland. This was a very important time in my life, because it convinced me that addressing biologic and medical questions in a disciplined scientific manner was what my life voyage should be. That voyage led me initially, through Woodward's contact, to work a summer in Joe Smadel's unit at Walter Reed (Smadel being one of the deans of American virology) and to meet several times with Carleton Gajdusek and then John Enders at Harvard, who pointed me to Frank Dixon at Scripps in La Jolla, California, for postdoctoral training. Dixon was among the founders of modern immunology and a pathfinder for immunopathology. Training by and association with Dixon and his other postdoctoral fellows, my independent position at Scripps, early polishing by Karl Habel (a superb senior virologist who left the National Institutes of Health and came to Scripps), and the gifted postdoctoral fellows who joined my laboratory over four decades form the log of my scientific voyage. The strong friendships and collaborations developed with other young but growing experimentalists like Bernie Fields and Abner Notkins are the fabric of the tale I will weave and were pivotal in the establishment of viral pathogenesis as a discipline.

摘要

我的这段探索之旅始于初中,当时我深受阿瑟·柯南·道尔笔下的夏洛克·福尔摩斯、珀西瓦尔·克里斯托弗·雷恩的《美丽的容貌》以及保罗·德克鲁伊夫的《微观世界的探索者》的影响,梦想成为一名探险家。我的出生地是曼哈顿(母亲是一名时尚模特,父亲从事零售行业),后来我前往阿拉巴马大学塔斯卡卢萨分校读大学,在那里,我不仅对历史和英国文学产生了浓厚的兴趣,还学习了足够的生物学、化学和遗传学知识,为进入医学院做准备。在马里兰大学医学院的第二年,通过 Theodore(Ted)Woodward 和 Sheldon(Shelly)Greisman 等医学专家以及 Charles Weissmann 在病毒学和微生物学方面的指导,我发现了解人们患病的原因和方式比识别和治疗他们的疾病更令我感兴趣。虽然我在诊断和治疗方面已经很熟练,但在大二结束时我还是离开了医学院,希望对生物学和化学有更基本的了解。我通过在约翰霍普金斯大学麦科勒姆-普拉特研究所攻读生物化学博士学位并在马里兰大学研究立克次体毒素来实现这一目标。这是我生命中非常重要的一段时光,因为它使我坚信,以严谨的科学方式解决生物学和医学问题才是我人生之旅的意义所在。这段旅程最初是通过 Woodward 的联系,让我在 Walter Reed 的 Joe Smadel 实验室度过了一个夏天(Smadel 是美国病毒学的院长之一),并多次与 Carleton Gajdusek 和后来的 John Enders 在哈佛会面,他们为我指明了在加利福尼亚拉霍亚的 Scripps 研究所找 Frank Dixon 做博士后培训的方向。Dixon 是现代免疫学的奠基人之一,也是免疫病理学的先驱。我在 Dixon 及其博士后研究员的指导下进行培训,并在 Scripps 研究所担任独立职位,早期还得到了 Karl Habel(一位出色的高级病毒学家,他离开美国国立卫生研究院来到 Scripps 研究所)的指导,以及在过去四十年里加入我实验室的才华横溢的博士后研究员,他们共同构成了我科学探索之旅的日志。我与其他年轻但不断成长的实验家,如 Bernie Fields 和 Abner Notkins 建立了深厚的友谊和合作关系,这些关系是我将讲述的故事的基础,也是病毒发病机制成为一门学科的关键。

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