一步之遥,八年光阴:丙肝病原体的发现到证明之路

Not-So-Low-Hanging Fruit:Journey from Identifying HCV to Proving It Pathogen of Hepatitis C

2020年的诺贝尔生理学或医学奖授予了在发现丙肝病毒(HCV)方面作出突出贡献的哈维·阿尔特(Harvey J.Alter)、迈克尔·霍顿(Michael Houghton)和查尔斯·赖斯(Charles M.Rice)。然而,从1989年霍顿捕获HCV到1997年赖斯证明HCV能引发肝炎,间隔了8年时间。这看似一步之遥的距离何以耗时如此之久?文章通过回顾文献,对这一时期的研究脉络进行了梳理,明确了包括赖斯团队在内的不同研究者对于推进HCV相关认识所作的具体贡献。同时,针对研究过程中的两个关键节点——病毒RNA基因组3′末端的准确测序和感染性分子克隆的建立,文章从技术储备、路径依赖和目标定位的角度分析了赖斯团队为何能在科学研究竞争中拔得头筹。

The Nobel Prize in Physiology or Medicine 2020 was awarded jointly to Harvey J.Alter,Michael Houghton,and Charles M.Rice for their contributions in the discovery of hepatitis C virus(HCV).However,eight years lapsed between Houghton hunting down the virus in 1989 and Rice proving HCV alone could cause hepatitis in 1997.How did this seemingly low-hanging fruit turn out to take so long?We reviewed literature to piece together studies during those years,and determined contributions by different groups(Rice’s group included).Through a close look into its performance at two milestones(determining the 3’-terrminal sequence of HCV genome RNA and constructing an infectious molecular clone),we analyzed,from dimensions of technology stack,path dependence,and goal setting,why Rice’s group leapfrogged its competitive peers.