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Nature:NgAgo争议再升级——围绕同行评议的相关论文展开

 空明苑 2016-11-27

Nature此篇报道是对NgAgo争议的回顾。

编译BioArt

北京时间11月24日凌晨,Nature 发布了一则题为NgAgo gene-editing controversy escalates in peer-reviewed papers(《 同行评议论文发表,NgAgo争议升级》)的报道。文章作者依然是Nature亚太地区记者David Cyranoski,此前他也在Nature写过一篇关于NgAgo争议的报道。

Nature:NgAgo争议再升级——围绕同行评议的相关论文展开

该文报道的主要内容是最近两篇有关NgAgo经过同行评议的学术论文,一篇是 Cell Research 发表的在斑马鱼中关于NgAgo的研究,来自南通大学等单位;另一篇则是Protein&Cell 发表的20名科学家联署的直接质疑NgAgo的Letter型文章。

报道在描述 Protein & Cell 的论文时提到,20位学者所在的实验室都尝试重复韩春雨的实验,但是无一成功,其中还有八个实验室严格按照韩所提供的实验方法和材料对相同的基因位点做了进一步的尝试,然而最终还是没能够重复出来。(Eight of the labs then tried again, adhering as closely as possible to Han’s experiment, using genetic materials provided by Han, targeting the same genes and also applying the technique to human cells.They all failed.)

报道还提到 Protein & Cell 的论文对韩春雨所在的团队提出了强烈要求,呼吁韩澄清围绕NgAgo发生的一系列事情,并尽可能提供所有必要的细节以便重复实验。但是Protein & Cell 的论文作者之一、北京大学魏文胜教授已经做出了明确的判断,那就是NgAgo根本不工作。(Wensheng Wei......has already made his mind up about NgAgo. “It simply doesn't work, period,” he says.)

Protein & Cell 杂志的执行编辑(managing editor)Zhang Xiaoxue 接受Nature 的采访时说,他们的杂志之所以快速出版这篇联署论文,主要是因为关于NgAgo的工作引发了持续讨论。她说:“在中国,这不仅仅是一个科学问题,同样还是一个伦理和政治问题”。(Zhang Xiaoxue......says that the journal made an effort to publish the NgAgo paper quickly because of the ongoing debate over the work. “In China, it’s not just a scientific issue. It’s also an ethical and political issue,” she says.)

接下来,Nature 这篇报道分三个部分展开:

1

Cyclops eyes

(Cyclops eyes 意为古希腊神话中独眼巨人的眼睛,此处指代 Cell Research 相关论文中使用NgAgo对定点基因进行敲低得到的斑马鱼表型。见下图)

Nature:NgAgo争议再升级——围绕同行评议的相关论文展开

报道说,南通大学的刘东博士回应称,他们在斑马鱼中使用NgAgo技术并没有实现目的基因的基因编辑,而只是降低了基因的表达;刘还提到在斑马鱼中NgAgo技术或许可以成为基因敲低的替代工具,而且显得更加便宜。但 Nature 随即评论道,如果刘的说法是正确的,那么这意味着NgAgo技术导致斑马鱼产生的表型无法永久遗传下去,也就是说NgAgo在这里并不能被考虑成一个基因编辑工具。(The lead author, Liu Dong, ...... offers an explanation: theNgAgo molecules clamp onto the genome but instead of cutting the target gene, just reduces its expression. Because the NgAgo protein can be easily prepared in the laboratory, Liu says that this capability could make it acheaper,more accessible alternative to current methods of temporarily blocking gene function in zebrafish.But if he is right, then NgAgo would not make permanent changes that are passed on to the next generation and would therefore not be considered a gene-editor.

刘东表示,“NgAgo可能有个新用途,可以当成一个廉价工具,用来抑制基因表达而不是编辑基因”。(he says, it raises the possibility ofa new use for NgAgo, as a cheap tool to block but not edit genes.

此前批评过韩春雨论文的遗传学家 Lluis Montoliu (来自西班牙国家生物技术研究中心) 在接受Nature采访时表示,这篇经过同行评议的论文其实是确认了NgAgo不能被当成一种基因编辑工具”, “一定要强调这一点”。(This is another report, now published in a peer-reviewed journal, confirming that NgAgo does not work as gene editor. ... This needs to be highlighted.

2

Too hot?

澳大利亚国立大学(Australian National University)的遗传学家Gaetan Burgio曾在网上发帖公布自己重复NgAgo实验失败,称自己根本不相信NgAgo能在韩春雨和刘东的实验所用的温度下起作用,因为实验的温度远远低于细菌存活所需的温度。(...he doesn’t believe that NgAgo can function at the temperatures used in either Han’s or Liu’s experiment. Both were carried out at much cooler temperatures than the environment in which the protein’s source — a bacterium — lives.)报道说,Burgio认为刘东观察到的斑马鱼异常是与NgAgo活性无关的其他毒理作用所致;刘东则相信NgAgo可以阻断基因表达,但同时他也承认这需要更多的证据,目前他正在收集相关的证据。(Burgio thinks the zebrafish abnormalities might have formed because of a toxicity unrelated to the activity of NgAgo. Liu says his data convince him that NgAgo can reliably block genes, but acknowledges that he needs more evidence to show this conclusively. He says he is working on assembling that now.

此前,韩春雨曾向 Nature 表示他发现了一个其他人在重复NgAgo实验时没有注意到的问题,这可以解释重复实验为什么失败。在本篇报道中,韩声称自己目前正在进一步验证,之后会发表数据和实验步骤来回应批评者。韩说:“我现在不能说问题是什么,因为媒体会一窝蜂来打扰我,我还需要点时间。” (He says that he is currently running confirmatory experiments so that he can publish data and a protocol that satisfies his critics. “I cannot say right now because the media in China jumps on everything I say,” he told Nature. “I need a little bit of time.”

Nature Biotechnology (发表韩春雨论文的杂志)的发言人称质疑韩春雨论文的一些个人和组织已经联系了杂志社,杂志社正慎重处理这些质疑。报道引用了发言人的原话:“我们对韩春雨论文的调查仍在继续。” ( A spokesperson for the journal that published his paper, Nature Biotechnology, said that a number of individuals and groups critical of Han’s NgAgo paper had contacted the journal, and that it has considered or is considering them carefully, alongside any published critiques of the research. “Our investigations into the paper are continuing at this time,” says the spokesperson. )报道特地说明Nature 新闻的编辑团队和Nature Biotechnology 的编辑是相互独立的。(Nature Biotechnology is editorially independent of Nature’s news team and is owned by Nature’s publisher Springer-Nature.

3

NgAgo in action

报道提及了两位曾声称证实NgAgo技术的匿名科学家。一位曾向 Nature 透露他已证实韩的发现,但没有发布实验数据,现在,他表示正使用NgAgo进行相关研究,希望不久就能发表论文。但另一位,曾提到获得NgAgo初步阳性结果,现在却表示“数据有些模棱两可,难以下结论”。报道称,这些科学家都不希望署名,因为担心卷入这场论战。(One of the few scientists who previously told Nature he had corroborated Han’s findings — but has not published these results — now says that he is using NgAgo for experiments related to his research, and that he hopes to publish soon. But another who previously noted positive initial results with NgAgo says now that the “data are confusing” and “we cannot make a conclusion”. Neither wanted to be named for fear of being dragged into the controversy.)

报道还提到,关于NgAgo本身以外的纷争在于河北科技大学因此成立的基因编辑中心,涉及由地方政府出资2.24亿的一项科研资助。报道引用了学术打假斗士方舟子的原话:“如果没有这篇 Nature Biotechnology 的文章和此后天花乱坠的社会热议,学校很难获得如此大的资助。”(“Without Han's Nature Biotechnology paper and the hype after that, it's impossible for the school to get such huge funding to establish the gene editing research centre,” says Fang Shimin)方还表示,根据NgAgo专利的声明可以看出河北科大缺少基因编辑相关的专业知识。“如果韩的发现不能被重复,这项资助的合理性就会大打折扣”。(He says that aside from Han’s NgAgo claims, the university lacks gene-editing expertise.So if Han's work doesn't stand up, “the centre will lose its legitimacy”.

在采访中,魏文胜教授对建立研究中心的看法与方舟子类似。他说:“基因编辑这样热门的领域建立研究中心并不是坏事,但建立的理由却仅仅是韩春雨的一篇论文。” (Wei too is critical of the decision to build the gene-editing centre, which he also attributes to the excitement over Han's paper. “It’s not a bad idea to have one in China considering that it is such a hot area,” he says, “but the only reason such centre is built in Hebei is because of Han’s publication.”

最后,河北科技大学谢绝了Nature新闻团队采访有关设立研究中心事宜的请求。(The university has declined the Nature news team’s requests to discuss the centre.

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