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通过Argonaute酶回收基因编辑的研究说明了媒体时代的出版后同行评议的重要性。
在这个问题上，Chunyu Han及其同事收回了一篇发表于2016年5月的论文，声称可以使用来自古细菌的天门冬氨酸杆菌的Argonaute蛋白（NgAgo），由短的5'磷酸化单链DNA引导，以产生双链断裂并编辑人基因组（Nat.Biotechnol.34,768-773，2016）。虽然这篇文章最初受到研究人员的热情和媒体关注，但是由Twitter，博客和其他社交媒体推动，其重现性的猜测迅速增长。去年十一月份，这本杂志发表了一份关于社论的编辑表达，以提醒社群了解这些重复性问题。争议的最终解决需要在多个月内从几个群体中产生额外的实验数据。现在发布的撤回证明了全球许多实验室投入的大量时间，精力和资金，旨在澄清NgAgo的功能。
去年出版以来韩文的影响很难夸大，特别是中国文献来源。中国媒体的报道广泛，头条新闻揭示了一个全新的基因编辑系统的发现。 NgAgo的报告很容易是去年中国覆盖率最高的论文;据媒体监视器Meltwater介绍，近四千个中国新闻报道在刚出版的头两个月引用了汉文。
NgAgo产生的兴奋主要集中在补充或甚至取代CRISPR-Cas9基因编辑系统的潜力。 NgAgo承诺仅需要单个靶序列（Cas9需要靶序列和附加相邻识别（PAM）序列）的基因编辑。更重要的是，初步数据表明提高了指南的稳定性（DNA与Cas9的RNA相比）具有优势，提高了特异性，减少了基因组的脱靶编辑和改善了基因组GC富集区域的活性。所用的试剂更容易合成和处理。
如果所有这一切听起来都不正确，去年夏天越来越多的实验室再现汉族文献报道的基因组编辑活动的失败开始引起疑问。该论文成为基因组编辑会议，新闻组和电子邮件列表中热门讨论的话题。新闻界通知不久之后，就初次报告的有效性提出了索赔和反诉。自然生物技术的内部图像完整性筛选过程在汉族论文中没有发现明显的异常现象，三位外部评审人员重新审视了这一数据。
同时，自然生物技术与社区保持联系，正在努力复制论文。最终，编辑们能够将三个独立团体的工作协调到一个同行评议的反驳论文（Nat.Biotechnol。35,17-18,2017）。随着这些数据的出现，我们有足够的理由通过出版“关注问题的编辑表达”来提醒我们的读者潜在的问题，该表达现在与原始论文在线一起出现，这是两位作者支持的一个步骤，包括汉。
我们还询问作者是否可以清楚社区为什么难以复制其结果。相应地，去年十二月，汉族及其同事以及数名额外的独立小组联系了该杂志，提供了声称重现NgAgo基因编辑活动的新资料。当时，这些数据被编辑者判断得太过初步，外部评论者有权出版。我们决定给原作者和新团体更多的时间收集更多的实验证据来加强他们的主张。
现在，在原始报告发表一年多以后，我们了解到，报告初步成功的独立团体，无法将其初步数据提升到可发布的水平。同样，在征求专家评审员的意见后，我们得出结论，汉族及其同事的最新数据不足以抵制与其初步调查结果不符的大量证据。我们现在相信，汉族和同事决定撤回该文件是支持公布记录的完整性的最佳方法。
NgAgo论文的出版不是科学进程的结束，而是一开始。像文献中出现的任何其他报告一样，更广泛的研究团体是测试方法，识别潜在的错误来源，验证试剂和优化测定。在这种情况下，几十个专门的人员正在通过公布的细节
Retraction of a study claiming gene editing via an Argonaute enzyme illustrates the importance of post-publication peer review in the age of 24/7 media.
In this issue, Chunyu Han and colleagues retract a paper published in May 2016 claiming that an Argonaute protein (NgAgo) from the archaea Natronobacterium gregoryi can be guided by short 5′ phosphorylated single-stranded DNAs to generate double-strand breaks and edit the human genome (Nat. Biotechnol. 34, 768–773, 2016). Although the paper was initially greeted with enthusiasm from researchers and intense media interest, speculation as to its reproducibility quickly grew, fueled by Twitter, blogs and other social media. Last November, this journal issued an Editorial Expression of Concern to alert the community to these reproducibility questions. Final resolution of the controversy necessitated the generation of additional experimental data from several groups over many months. That a retraction is now issued is testament to the considerable time, effort and funds invested by many laboratories around the globe that have sought to clarify NgAgo's function.
It is hard to overstate the impact of the Han paper following its publication last year, especially in China, where the paper originated. Coverage in the Chinese media was extensive, with headlines heralding the discovery of an entirely new gene editing system. The NgAgo report was easily the most widely covered paper in China last year; according to media monitor Meltwater, nearly 4,000 Chinese news stories cited the Han paper in just the first two months after publication.
The excitement generated by NgAgo centered on its potential to complement, or perhaps even supersede, the CRISPR–Cas9 gene editing system. NgAgo promised gene editing that required only a single target sequence (Cas9 needs both the target sequence and an additional adjacent recognition (PAM) sequence). What's more, initial data suggested advantages in terms of enhanced stability of the guide (DNA compared with RNA for Cas9), improved specificity, reduced off-target editing of the genome and improved activity in GC-rich regions of the genome; and the reagents used were easier to synthesize and handle.
If all this sounded too good to be true, the failure last summer of an increasing number of laboratories to reproduce the genome editing activity reported in the Han paper started to raise doubts. The paper became a hotly discussed topic at genome editing conferences, news groups and e-mail lists. It didn't take long before the press took notice. Claims and counterclaims regarding the validity of the initial report were exchanged. Nature Biotechnology's internal image integrity screening process found no obvious anomalies in the Han paper, a finding echoed by three external reviewers who reexamined the data.
Meanwhile, Nature Biotechnology kept in contact with the community about ongoing efforts to replicate the paper. Ultimately, the editors were able to coordinate the work of three independent groups into a single peer-reviewed refutation paper (Nat. Biotechnol. 35, 17–18, 2017). With these data in hand, we then had sufficient cause to alert our readers to potential problems with the paper by publishing the Editorial Expression of Concern, which now appears alongside the original paper online—a step that was supported by two of the authors, including Han.
We also asked the authors if they could shed light on why the community was having difficulties reproducing their results. Accordingly, last December, Han and colleagues and several additional independent groups who contacted the journal provided new data claiming to have reproduced NgAgo gene editing activity. At the time, these data were judged too preliminary by the editors and an external reviewer to warrant publication. We decided to give the original authors and new groups more time to gather additional experimental evidence to bolster their claims.
Now, more than a year after the publication of the original report, we have learned that the independent groups that reported initial success in reproducing the results have not been able to bolster their preliminary data to a publishable level. Similarly, after seeking feedback from expert reviewers, we have concluded that the latest data from Han and his colleagues are insufficient to counter the substantial body of evidence that contradicts their initial findings. We are now convinced that the decision of Han and colleagues to retract the paper is the best course of action to support the integrity of the published record.
Publication of the NgAgo paper was not the end of the scientific process, it was the start. Like any other report that appears in the literature, it is the wider research community that tests methods, identifies potential sources of error, validates reagents and optimizes assays. In this case, it took dozens of dedicated individuals to work through the details of the published protocol and produce well-documented and controlled refutation studies (Protein Cell 7, 913–915, 2016; Nat. Biotechnol.35, 17–18, 2017; Cell Res. 26, 1349–1352, 2016; PLoS One 12, e0177444, 2017).
The NgAgo controversy also illustrates the pros and cons of social media. Clearly, these platforms were valuable for rapidly alerting the wider scientific community to problems with the paper. But they also raised expectations that issues with this paper were straightforward and could be solved quickly. Unraveling all the problems with the NgAgo editing claim didn't happen in weeks or a few months for a reason. Even simple experiments take weeks to prepare, perform, analyze and troubleshoot. It does not help that the efforts of those carrying out replication studies often go unrewarded—it is unglamorous, unfunded and thankless work.
Little wonder then that to a 24/7 media and public that desire quick, definitive answers, the process of post-publication peer review can seem frustratingly slow. But when it comes to biology, answers are often not definitive. And when it comes to replication studies, the one thing we know is that it takes time. In the case of NgAgo, the time has come and the data have spoken.
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