Two Decades of ASGCT: Dreams Become Reality.
Two Decades of ASGCT: Dreams Become Reality.
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ASGCT 的两个十年：梦想变成现实。
DOI：
10.1016/j.ymthe.2017.04.011
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发表时间：
2017
期刊：
影响因子：
--
通讯作者：
Dunbar,CynthiaE
中科院分区：
文献类型：
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作者：
Dunbar,CynthiaE
20世纪90年代初是进入基因治疗领域的一个激动人心的时期，开始了第一批临床试验，成立了该领域的第一家生物技术初创公司，在啮齿动物模型和体外研究的某些类型的人类细胞中取得了令人鼓舞的结果，人们对此持乐观态度。就我个人而言，我从Art Nienhuis实验室的博士后职位一跃而来，作为一名新晋的终身教职员工，负责了首批基因标记临床试验。然而，到1995年，我们中的大多数人开始意识到，尽管这些概念很优雅，我们也很热情，但事情并没有那么容易。早期试验显示，基因校正后的细胞几乎没有持久性，也没有可靠的临床改善证据。当时的NIH主任Harold Varmus委托了一个由Stewart Orkin和Arno Motulsky担任主席的蓝带小组，目的是检查基因治疗的现状，并为NIH未来在该领域的支持提供建议。1995年12月发表的这份报告的结论相当发人深省，其中着重指出缺乏临床疗效、过分夸大实验室和临床研究结果，以及对疾病病理生理学和基因转移载体的基础科学缺乏充分了解所造成的负面影响。该报告的结论特别呼吁对这些基本问题进行更多的研究，从而导致精心设计的探索性临床试验，以及在必要的研究领域改进培训，以及科学家与公众之间更好、更诚实的沟通。在这份报告的背景下，以及它为未来的研究设定的更具挑战性的门槛，1996年成立一个专注于基因治疗的协会可能是一个令人惊讶的时间。我清楚地记得，1996年初，在报告发表几周后，我坐在新墨西哥州陶斯一家酒吧角落的桌子旁，与其他来自基斯顿研讨会的发言者一起，题为“在遗传疾病和癌症中使用造血干细胞进行基因治疗”。George Stamatoyannopoulos，我的导师Art Nienhuis，我在NIH的同事David Bodine和Michael Blaese， Don Kohn和Scott mccivor是我记得在我们起草美国基因治疗学会（ASGCT）成立计划时在场的一些名人。我们觉得有必要开始将我们的努力专业化，把研究许多不同目标基因疗法的不同研究人员聚集在一起，他们都在努力解决同样的问题，即基因传递到靶细胞的效率低下，以及转基因的表达受限或失调。我们希望ASGT能成为一个分享信息的地方；让公众、资助者和监管机构参与进来；并激励学生和博士后进一步追求他们在该领域的兴趣。此时，欧洲人和日本人都已经成立了社团，并举行了第一次年度会议。
The early 1990s was an exciting time to enter gene therapy, with initiation of the first set of clinical trials, the founding of the first biotechnology startup in the field, and optimism based on encouraging results in rodent models and some types of human cell studied in vitro. I personally jumped right from my postdoc in Art Nienhuis’s lab to running several of the first gene marking clinical trials as a newly-minted tenure-track faculty member. However, by 1995, most of us were beginning to realize it would not be quite so easy, despite the elegance of the concepts and our enthusiasm. The early trials showed little persistence of genetically corrected cells and no credible evidence for clinical improvement. Harold Varmus, then director of the NIH, commissioned a blue-ribbon panel chaired by Stewart Orkin and Arno Motulsky with the aim of examining the current status of gene therapy and providing recommendations for future NIH support in the area. The conclusions of the report, issued in December 1995, were quite sobering, focusing on the lack of clinical efficacy, the overselling of results from both laboratory and clinical studies, and the negative impact of a lack of sufficient understanding of both disease pathophysiology and the basic science of gene transfer vectors. The report conclusions specifically called for more research into these basic questions, leading to well-designed exploratory clinical trials, along with improved training in the necessary research areas, and better and more honest communication between scientists and the public.In the context of this report and the even more challenging bars it set for future research, 1996 was perhaps a surprising time to be founding a society focused on gene therapies. I vividly remember sitting around a table in the corner of a bar in Taos, New Mexico in early 1996, a few weeks after the report was issued, with other speakers from a Keystone Symposium entitled “Gene Therapy with Hematopoietic Stem Cells in Genetic Diseases and Cancer.” George Stamatoyannopoulos, my mentor (Art Nienhuis), my colleagues at the NIH (David Bodine and Michael Blaese), Don Kohn, and Scott McIvor were some of the notables I recall being present as we drew up plans for the founding of the American Society for Gene Therapy (ASGCT). We felt the need to begin to professionalize our endeavors, bringing together the quite diverse investigators who had been working on many different targets for gene therapies all struggling with the same issues, ie, poor efficiency of gene delivery into target cells and limited or dysregulated expression of the transgenes. We hoped ASGT would serve as a place to share information; engage the public, funders, and regulators; and stimulate students and postdoctoral fellows to further pursue their interest in the field. By this time, both the Europeans and the Japanese had already formed societies and held their first annual meetings.