诺贝尔奖为什么没有给发明丙肝病毒治疗的人？
在评价病原微生物领域里的贡献时，发现病毒或病原体是最为重要的，这就是为什么诺贝尔委员会选两位在丙肝病毒领域的pioneers的原因，药物治疗全是建立在病毒发现和Charles Rice发现丙肝病毒复制模板的基础上的。这也是为什么我说石正丽和张永振的贡献应该获得诺贝尔奖的原因，现在HIV,乙肝病毒，丙肝病毒和黄热病病毒，都因发现病毒而获得诺贝尔奖，为什么新冠不能？如果像Lasker那样包括丙肝病毒的药物研发，至少还应该包括更多的两位，这样诺贝尔奖就会出现分配不均的情况。换一个角度思考问题，Lasker把发现丙肝病毒的科学家排除在外，更加不公平。
现在华大分子微生物系的主任解释得更清楚了，我也去读了Charles Rice的Science原文。Michael Houghton在1989年得到丙肝病毒全序列后，这个病毒一直不能培养，也不可能有体外的动物模型，更谈不上药物的筛选。所以全基因序列只能供诊断用，也因此阻断了输血造成的丙肝流行。
Charles Rice开始是做黄热病病毒的，这个病毒与丙肝病毒同源。更为关键的是Rice是个杰出的分子生物学家，他从黄热病毒领域让一些博士后研究丙肝病毒，只是用很少的精力就找到了金矿。原来1989年发表的丙肝病毒是突变了的或变异了的病毒株，或许至今没有丙肝疫苗就是因为丙肝的突变。Charles Rice和俄罗斯博士后开始基因工程丙肝病毒很小的基因组（新冠大很多），他们在丙肝病毒的3‘端加了几乎是一倍的末端长度，就是使用他们手上的黄热病病毒的片段，同时他们在丙肝病毒的基因组中间也置入几个点突变。这样加工已经发表的丙肝序列后，他们居然发现丙肝病毒可以在体外培养，然后将活病毒注入猴子肝内，机体产生的转氨酶等肝炎标志物迅速增高，这样他们复制了有毒性的活病毒。
顺带分享华大医学院院长和众多病毒学同行的谈话。华大校长更是总结Charles Rice是整个华大的第25位诺贝尔奖得主，也是医学院的第19位诺贝尔奖得主。这些数据是一些国家的几十倍，所以科学落后国家的人们在吹牛时还是应该humble点。
Charles Rice现在仍然保留华大的Adjunct Professor的头衔，他对圣路易斯亲近的部分原因是现任太太也是华大的，应该现在还在他的洛克菲勒实验室。这是朋友的留言：“也来蹭一下名人热度，二十多年前在Wash-U上班时经常见到Charles Rice, 最常见是在每周的Virology Journal Club, 那时他50岁不到，已是正教授，留有络腮胡子，比实际年龄看上去要老，记得我的一次presentation, 他还提了一个问题。还有个八卦是他那时和Skip实验室的MD fellow Peggy McDonald在dating, 后来Peggy也随着他去了纽约，不知道现在他们还是不是在一起”
这些是在诺贝尔医学奖的颁奖机构Karolinska研究所任职的同济校友的留言，让我们知道一些内部的资讯，也留作以后参考：“诺奖评选的最后阶段就是我们学校的几十个教授投票，我认为不是每个投票的人都具备较高的鉴赏能力。换句话说，这活让我去干我也能胜任[Grin]。但是前期的筛选是由少数的几个人完成的。我是说投票的活我可以干😂只是举手而已。说来寒酸，诺贝尔医学生理学奖评审机构其实就只有一个全职的工作人员，她负责一切具体杂事。KI的教授都可以提名，委员会（committee）大概有6个人负责前期的筛选工作，把名单缩减到个位数，然后由Assembly（50个KI教授）投票。我真心觉得投票这活没啥技术含量，Assembly里面有几个人我知道的，窃以为水平一般般😂”
下面为来自华大的新闻报道：
“Charlie is an absolutely brilliant scientist and a wonderful human being who has made a deep impression on all those who have worked with him,” said David H. Perlmutter, MD, executive vice chancellor for medical affairs and the George and Carol Bauer Dean of Washington University School of Medicine.“His work on hepatitis C has improved the lives of so many people, and here presents the best of what Washington University stands for.”
“At Washington University, Charlie Rice recognized that one problem in developing genetic tools to study hepatitis C virus was that we lacked the correct sequence of the viral genome,” said Sean Whelan, the Marvin A.Brennecke Distinguished Professor and head of the Department of Molecular Microbiology. “Extending on his studies from a related virus, yellow fever virus, he identified a highly conserved sequence element at one end of the viral genome. This allowed Dr. Rice to engineer a correct copy of the viral genome which turned out to be infectious in primates. This paved the way for fundamental studies of how the virus replicates, which led, ultimately, to drugs that interfere with its replication. His visionary research helped pave the way for development of a cure for HCV. He has inspired a generation of virologists.”
Rice and others went on to identify the genetic and molecular machinery the virus employs to infect cells, multiply and cause disease — all potential targets of antiviral drugs. Rice developed a system to screen drugs that block key steps in the viral life cycle, eventually leading to the development of curative drugs for hepatitis C virus infection.
Rice is the 19th scientist associated with Washington UniversitySchool of Medicine to be honored with a Nobel Prize. Across WashingtonUniversity, 25 current or former faculty members or trainees have received a Nobel.
“Charlie Rice is an amazing person, a spectacular scientist, and a wonderful colleague,” said Scott J. Hultgren, the Helen L. StoeverProfessor of Molecular Microbiology. “He did work that led to the Nobel Prize here in the Department of Molecular Microbiology, creating the first infectious viral genome for in vitro replication. He was a phenomenal leader and colleaguehere at Washington University.” Added Washington University collaborator Michael S.Diamond, MD, PhD, the Herbert S. Gasser Professor of Medicine: “For many decades, Dr. Rice has been a pioneer in the field of molecular biology and genetics of many emerging RNA viruses including flaviviruses, alphaviruses, and hepaciviruses. His seminal studies on hepatitis C virus directly led to the screening and identification of direct-acting antiviral drugs that have resulted in a cure for so many people around the world. His creative research on cellular host-defense responses to viruses have triggered the development of new classes of host-directed antiviral agents. Moreover, he has mentored and trained a generation of virologists who are now at the vanguard of the field. This is truly a deserving honor for a visionary scientist.”
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