n******g
发帖数: 17225 | 1 陷入争议漩涡一年之后，河北科技大学副教授韩春雨主动撤回了关于新基因编辑技
术的论文。当初刊发其论文的《自然·生物技术》3日发表社论说，“我们现在确信韩
春雨的撤稿决定是维护已发表科研记录完整性的最好做法。”
此事给予我们的最大启示，也是下一步探寻真相的原则，莫过于科学的问题要用科
学的态度来对待。
让事实说话，这是科学研究的基本原则。科学是老老实实的学问，来不得半点虚伪
和骄傲，需要的是诚实和谦逊的态度。科学研究必须扎扎实实，分毫含糊不得。
近年来，随着科学研究日益细分，“隔行如隔山”的情况越来越多。这导致许多重
大科研成果公布后相当一段时间里，业界既无法证实，也无法证伪。这样的事例在国内
外科技界都不鲜见。
在这样的背景下，如果主动迎合全社会对快出成果、出大成果的迫切期待，好大喜
功，人为夸大，甚至造假，那么很容易形成利益链条，错上加错，愈陷愈深。反之，因
认识有限而轻易否定一个成果，同样会迟滞科研工作，也是百害而无一利的。
在如何正确对待科研成果这个问题上，我们要有“热”期盼，更要作“冷”思考。
在“一鸣惊人”之后，所在单位、主管部门是不是非要一拥而上，锣鼓喧天？能不能把
关爱更多投到那些“十年不鸣”、默默耕耘的科学家身上？我们的科研考评机制、科研
资源分配体系是不是应该及时落实改革要求，真正让“坐冷板凳”的人不必为出成果心
急火燎，能够踏踏实实搞研究？
求真务实，永远是对待科学问题的基本态度，是科学界的共同价值观，是不可退让
的共同底线。接下来，相信中国科技界会以科学的态度对这一成果进行充分地论证。在
科学问题上，我们反对功利和浮躁，但不能因此而陷入另一种功利和浮躁之中。（完） | n********g
发帖数: 6504 | | p******g
发帖数: 8316 | 3 哈哈哈
【在 n********g 的大作中提到】
: 尼玛比我早发了几个小时。连5毛版权费都讨不到
| t***h
发帖数: 5601 | 4 Nature Biotechnology | Editorial | doi:10.1038/nbt.3938
Time for the data to speak
Published online, 2 August 2017
http://www.nature.com/nbt/journal/vaop/ncurrent/full/nbt.3938.html
在社论中，一项宣称通过Argonaute酶实现基因编辑的研究被撤回，这显示了论文
发表后的同行评议在全天候媒体时代的重要性。
韩春雨的这篇论文自去年发表后所产生的影响力，再怎么夸张地说也不为过，尤其
是在论文的来源地中国。中国媒体纷纷进行报道，以大标题宣告一项全新基因编辑系统
的发现。这无疑是一篇中国去年被报道最多的论文；媒体监测公司融文（Meltwater）
的数据显示，仅在论文发表后的最初两个月，就有将近4000篇相关的中文新闻报道。
NgAgo的轰动之处集中在它有可能补充，甚至取代CRISPR/Cas9基因编辑系统之一点
上。NgAgo有望以一个目标序列进行基因编辑（Cas9不仅需要目标序列，还需要另外一
个附近的识别PAM序列）。而且，初始数据还显示了它在其它方面的优势，如引物的稳
定性更强（DNA相对于Cas9采用的RNA），增强特异性，减少基因组编辑脱靶，改善在基
因组富含GC区域的活性，以及使所用的试剂更易于合成和处理。
如果说这一切都听上去太过美好而令人难以置信，那么去年夏天以来，随着越来越
多的实验室无法重复该论文所报告的基因组编辑功能，质疑声便开始出现了。在各种基
因组编辑会议上，在新闻讨论组和电子邮件中，这篇论文成为最热话题之一。这很快便
引起媒体注意，有关该初始报告有效性的正反两方面的声音开始交锋。我们内部的图像
完整性筛查没有发现韩春雨论文的明显异常，复查数据的三位外部评审人也持相同观点。
在此期间，《自然·生物技术》一直与科研界保持联络，关注各种为重复论文所做
的持续努力。最终，在编辑们的协调下，三个独立小组的成果形成了一篇单独的反驳性
论文，并通过了同行评议（Nat. Biotechnol.34, 768-773, 2016）。有了这些数据，
我们就有充分的理由去提醒读者留意该论文可能存在问题，我们将正式的“编辑部关注
”发表在该篇论文所在的网址上，此举得到包括韩春雨在内的两位论文作者的支持。
我们也询问了论文作者是否可以解答科研界为何难以重复他们的结果。于是，去年
12月，韩春雨及同事，还有另外几个与本刊联系的独立研究小组，提供了新的数据，称
已经重复了NgAgo基因编辑活性。当时，本刊编辑和一位外部评审人都判定这些数据太
过初级，不满足发表标准。因此，我们决定给这些原始论文作者和新的研究小组更多时
间来收集更多的能支持其论点的实验证据。
现在，距原论文发表已过去了一年多，我们了解到当初曾报告说初步成功重复出实
验结果的独立研究小组，无法强化初始数据，使其达到可发表的水平。类似的，在征求
专家评审人的反馈意见后，我们判定韩春雨及同事提供的最新数据不足以反驳大量与其
初始发现相悖的证据。我们现在确信韩春雨的撤稿决定是维护已发表科研记录完整性的
最好做法。
这篇有关NgAgo的论文发表出来，并不是科研过程的结束，而是开始。与任何其它
发表出来的报告一样，正是广大的科研共同体对相关方法进行了检验，识别潜在的错误
来源，验证试剂并优化试验。在本例中，有多位敬业的研究者个人对已发表实验方法的
各种细节进行检验，并完成记录翔实和有对照组的反驳性研究（Protein Cell 7, 913,
2016; Cell Res.26, 1349-1352, 2016; PLoS ONE, 12, e0177444, 2017）。
这篇NgAgo论文也显示了社交媒体的利与弊。显然，这些平台对于迅速提醒广大科
学界留意该论文可能存在的问题发挥了重要作用。但是，它们也抬高了人们的预期，以
为有关这篇论文的问题是直截了当，可以快速解决的。然而，关于NgAgo的各种问题是
无法在几个星期或几个月内就能澄清的，这是有原因的。即使是简单的实验也需要花费
数周来准备、实施、分析和解决出现的问题。另外于事无益的是，那些进行可重复性研
究的人，其付出的努力往往得不到回报，这样的工作单调乏味，没有资金支持，还吃力
不讨好。
难怪在希望得到快速、明确答案的全天候媒体和公众眼中，论文发表后的同行评议
流程似乎慢得让人沮丧。但是，当涉及生物学时，往往没有明确的答案。当研究重复性
时，有一点我们是知道的，那就是这需要花时间来做。就这篇有关NgAgo的论文而言，
现在是时候了，数据已经说话了。
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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