​绝对尴尬！诺奖得主《自然-化学》论文撤稿！傍牛人猛男的"自然牌"水性浪女也绝无脸红？

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前天，看到下面一篇《撤稿观察》发表的文章“”Definitely embarrassing:” Nobel Laureate retracts non-reproducible paper in Nature journal”（绝对尴尬：诺奖得主撤掉发表在《自然》杂志的不可重复论文），说2009年的诺奖得主之一、哈佛大学的教授 Jack W. Szostak 撤掉2016年发表在《自然-化学》的一篇论文。

Retraction Watch

”Definitely embarrassing:” Nobel Laureate retracts non-reproducible paper in Nature journal

with 8 comments

A Nobel Laureate has retracted a 2016 paper in Nature Chemistry that explored the origins of life on earth, after discovering the main conclusions were not correct.  

Some researchers who study the origins of life on Earth have hypothesized that RNA evolved before DNA or proteins.  If true, RNA would have needed a way to replicate without enzymes. The Nature Chemistry paper found that a certain type of peptide — which may have existed in our early history — made it possible for RNA to copy itself.

Jack W. Szostak —a professor of chemistry and chemical biology at Harvard University in Cambridge, Mass., who shared the 2009 Nobel Prize in Physiology or Medicine with Elizabeth Blackburn and Carol Greider  for their pioneering research on aging—told us he was “incredibly excited” when he “thought we had at least a partial solution to this problem,” which researchers have been working on for over 50 years.  

But in subsequent experiments, Tivoli Olsen — a member of Szostak’s lab — could not reproduce the 2016 findings. When she reviewed the experiments from the Nature Chemistry paper, she found that the team had misinterpreted the initial data: The peptide in question did not appear to provide an environment that fostered RNA replication.

The errors were “definitely embarrassing,” Szostak told us:

In retrospect, we were totally blinded by our belief [in our findings]…we were not as careful or rigorous as we should have been (and as Tivoli was) in interpreting these experiments.

Szostak added:  

The only saving grace is that we are the ones who discovered and corrected our own errors, and figured out what was going on.

Given the issues, the authors requested that the Nature Chemistry paper, “Oligoarginine Peptides Slow Strand Annealing and Assist&nbsp 41 38784 41 15927 0 0 7660 0 0:00:05 0:00:02 0:00:03 7657;Nonenzymatic RNA Replication ,” be retracted. This retraction marks the second in six months for  Nature Chemistry  after having none for eight years. The paper has been cited nine times, according to Clarivate An a lytics’ Web of Science .

A previous replication issue

In 2009, Szostak also retracted  a 2008 paper in  Proceedings of the National Academy of Sciences  after an outside researcher could not replicate the results. The retraction notice credited Katherine Berry, then a doctoral student at the University of California, Berkeley, for bringing the issues to their attention. (Full disclosure: RW’s Victoria Stern and Berry were roommates freshman year of college).

Berry, who’s now an assistant professor of biochemistry at Mount Holyoke in South Hadley, Mass., told us that she was interested in the PNAS research because it identified a potential inhibitor of the hepatitis C virus, and she wanted to explore how that inhibitor worked. Berry explained that the authors “were excited to collaborate and sent me peptides.”

But in follow-up experiments, Berry was unable to reproduce the findings. Berry presented her data to Szostak. Szostak, she said, “was really supportive and thankful of my efforts” and “took an active role” to correct the literature.” She explained that Szostak “immediately asked a postdoc in his lab to follow-up” on the PNAS work, and he “moved quickly to retract the publication” when the postdoc’s replication attempt also failed.

The paper, “Selection of cyclic peptide aptamers to HCV IRES RNA using mRNA display ,” has been cited seven times (including once by the retraction notice).

The notice

The no t ice  in Nature Chemistry provides a detailed account of what happened:

We the authors are retracting this Article because our efforts to repeat and follow up on the results have been unsuccessful. Specifically, we have been unable to reproduce observations suggesting that arginine-rich peptides allow the non-enzymatic copying of an RNA template in the presence of its complementary strand (Fig. 4e). We originally dismissed variability in these experiments as resulting from variability in the snap cooling of samples following thermal denaturation. However, we now understand that the data reported in the published article are the result of false positives that arose from an incorrectly designed experiment in which random errors, including transfer and concentration errors, affected the ratio of the concentrations of the RNA template and its complementary strand. This resulted in false positives that were misinterpreted as template copying in the presence of a complementary strand, where in reality these reactions did not contain enough complementary strands to completely inhibit the reaction.

Subsequent experiments suggested that arginine-rich peptides may not slow the reannealing of complementary strands (Fig. 3), and that what we had previously interpreted as a decrease in annealing rate was actually an artefact due to slow coalescence or strand exchange between droplets of RNA–peptide coacervate, as well as droplet coalescence and settling that led to decreased fluorescence intensity. Similarly, the changing circular dichroism spectra shown in Figure 2c, which were originally interpreted to be the result of a change in the global helical structure of RNA upon peptide binding, may also be an artefact due to, for example, loss of signal or light scattering. Although the binding of arginine-rich peptides to RNA does form condensed-phase droplets, and although most of the RNA does reside within the condensed phase, follow-up experiments to confirm that non-enzymatic RNA polymerization occurs within these coacervate droplets have been inconclusive (Fig. 5d).

The experiments showing that vesicles are stable in the presence of arginine-rich peptides (Supplementary Figure 26, by N. Kamat), and the failure of acidic peptides to condense RNA (Supplementary Figure 8, by K. Adamala) have been reproduced. However, since the main conclusions of our paper are incorrect, all of the authors are now retracting the Article. The authors would like to thank Dr Tivoli Olsen for her extensive efforts to unravel the errors in our Article and we apologize to the scientific community for any confusion arising from our publication.

Moving forward

Olsen, the researcher in Szostak’s lab who discovered the issue with the 2016 paper in Nature Chemistry, told us:

As a scientist the job is to troubleshoot. You can’t help nor can you ignore where that takes you. I fulfilled my obligation to insure that no one after me would waste their time on this.

Szostak told us that he plans to continue working to unravel “the problem of chemically replicating RNA:”

Although we are disappointed that that approach does not work, we are going back to the drawing board and looking into other ways of overcoming this roadblock.

笔者当时忙其它“正事”，没有时间翻译这篇“尴尬”新闻。好在只要沾上《自然》牌牛文、特别是还与诺奖得主挂上勾的话，总有人会灰常及时地写文章介绍这些新闻的。

这不，《科学网》就很快发表了一篇题为“科学网—由于不能重复结果，诺奖获得者Szostak愤怒地撤回PNAS等2篇文章”的博文。而且作者还姓刘，叫“刘盼”。

由于不能重复结果，诺奖获得者Szostak愤怒地撤回PNAS等2篇文章

已有 11208 次阅读 2017-12-6 12:19 |个人分类:文章介绍 |系统分类:论文交流 |关键词:诺贝尔化学奖，撤稿，Szostak，PNAS，Nature,Chemistry,不能重复

iNature：诺贝尔奖获得者Szostak在发现了主要结论并不正确之后，已经撤回了2016年在“自然化学”（Nature Chemistry）上发表的一篇探索地球生命起源的论文。

一些研究地球上生命起源的研究人员假设RNA是在DNA或蛋白质之前进化的。 如果这是真的话，那么RNA将需要一种不用酶进行复制的方法。 “自然化学”（Nature Chemistry）的论文发现，某种类型的肽 - 在我们早期的历史中可能已经存在 - 使得RNA自我复制成为可能。

美国马萨诸塞州剑桥哈佛大学化学与化学生物学教授杰克·W·索佐克（Jack W. Szostak）与伊丽莎白·布莱克本（Elizabeth Blackburn）和卡罗尔·格雷德（Carol Greider）分享了2009年度诺贝尔生理学或医学奖，他们对衰老的开创性研究告诉我们，他“令人难以置信 兴奋“的时候，他认为我们至少有一个解决这个问题的办法，”研究人员已经研究了50多年。

但在随后的实验中，Szostak实验室的成员Tivoli Olsen无法重复2016年的发现。 当她回顾Nature Chemistry论文中的实验时，她发现该团队误解了最初的数据：所讨论的肽似乎没有提供促进RNA复制的环境。

Szostak告诉我们这些错误“绝对令人尴尬”：

回想起来，我们完全被我们的信念所掩盖（在我们的发现中）......我们并不像我们本应该那样仔细或严格（和Tivoli一样）来解释这些实验。

Szostak补充说：

唯一的补救措施是我们发现和纠正我们自己的错误，并找出发生了什么事的人。

鉴于这些问题，作者要求撤回“自然化学”论文“Oligoarginine Peptides Slow Strand Annealing and Assist Nonenzymatic RNA Replication”。  据Clarivate Analytics的Web of Science报道，这篇论文被引用了9次。

以前的重复性问题

2009年，Szostak得知无法复制结果之后，撤回了2008年在“美国科学院学报”（Proceedings of the National Academy of Sciences）上的一篇论文。撤回通知书记录了伯克利加利福尼亚大学的博士生凯瑟琳·贝里（Katherine Berry）提出的问题。

Berry，现在是位于马萨诸塞州South Hadley的Holyoke的生物化学助理教授，她告诉我们她对PNAS的研究很感兴趣，因为它确定了一种潜在的丙型肝炎病毒抑制剂，她想探索这种抑制剂是如何工作的。贝瑞解释说，作者“很高兴合作，并发送肽”。

但在后续的实验中，贝瑞无法重现这一发现。贝瑞向Szostak提交了她的数据。她说，Szostak“对我的努力是非常支持和感激的”，并“发挥了积极的作用”来纠正这些文献。“她解释说，Szostak立即向PNAS工作的一个实验室博士后问了”而当博士后的复制尝试也失败时，他“迅速撤回了出版物”。

已经被引用七次（包括通过撤回通知一次）的论文“Selection of cyclic peptide aptamers to HCV IRES RNA using mRNA display,” has been cited seven times”。

声 明

“自然化学”的通知详细介绍了发生的事情：

我们这些作者正在撤回这篇文章，因为我们重复和跟进结果的努力是失败的。具体而言，我们一直无法重现观察结果，表明富含精氨酸的肽允许RNA模板在其互补链存在下的非酶复制（图4e）。我们最初认为这些实验中的变异性是由热变性后样品的快速冷却变化引起的。然而，我们现在了解到，发表的文章中的数据是由错误设计的实验引起的假阳性结果，其中随机误差（包括转移和浓度误差）影响了RNA模板浓度的比例及其互补性链。这导致了在互补链存在下被错误解释为模板复制的假阳性，实际上这些反应不含有足够的互补链来完全抑制反应。

随后的实验表明，富含精氨酸的肽可能不会减慢互补链的退火（图3），并且我们之前解释为退火速率下降的实际上是由于RNA小滴之间的缓慢聚结或链交换而造成的人工制品 - 肽凝聚层，以及导致荧光强度降低的液滴聚结和沉降。类似地，图2c中所示的改变的圆二色谱（其原先被解释为在肽结合后的RNA的全局螺旋结构的变化的结果）也可能是由于例如信号或光的损失散射。尽管富含精氨酸的肽与RNA的结合确实形成了凝聚相液滴，并且尽管大部分RNA确实存在于凝聚相内，但是后续实验证实在这些凝聚层液滴内发生非酶促RNA聚合反应尚无定论（图5d）。

这些实验表明囊泡在富含精氨酸的肽的存在下是稳定的（补充图26，由N.Kamat提供），并且酸性肽缩合RNA的失败已被复制（补充图8，由K.Adamala）。但是，由于我们论文的主要结论是不正确的，所有的作者现在都撤回了这篇文章。作者要感谢蒂沃利·奥尔森博士的广泛努力，以解决我们的文章中的错误，我们向科学界道歉，因为我们的出版物引起的任何混淆。

科学不断向前

Szostak实验室的研究人员奥尔森（Olsen）在2016年的“自然化学”（Nature Chemistry）杂志上发现了这个问题，他告诉我们：

作为一名科学家，工作是排除故障。 你不能帮助别人，但也不能忽视那些需要你的地方。 我履行了自己的义务，确保没有人会在这之后浪费时间。

Szostak告诉我们，他计划继续努力解开“化学复制RNA的问题：

虽然我们对这种方法不起作用感到失望，但我们正在回到制图板，并寻找克服这一障碍的其他方法。

注：主要来源于Retraction Watch网站。

原文链接

https://www.nature.com/articles/nchem.2551.epdf?shared_access_token=_6aqIqPczWW4tTT0RrSuIdRgN0jAjWel9jnR3ZoTv0NXtWCSXYjhBd2CLhe5OnX7S5ulLnul7cJtFXuLB_nqQmwDwQvwGwqRA7J5b2JygWGeMXhBtemYgNw7jyn3m6N4VAr23w-qiwN3hi60DwtWOA4VIG2FNUVvR6XRR1ibSn0%3D

http://www.pnas.org/content/105/40/15293.full

原文解析

http://retractionwatch.com/2017/12/05/definitely-embarrassing-nobel-laureate-retracts-non-reproducible-paper-nature-journal/

其实，这篇中文博文的题目是有些“离谱”，因为这位撤稿的诺奖得主还真的没有“愤怒”，只是绝对尴尬而已。

为什么要尴尬呢？笔者将撤稿声明 的全文复制如下，并把值得尴尬的一些细节用黑体标明：

Retraction: Oligoarginine peptides slow strand annealing and assist non-enzymatic RNA replication

• Tony Z. Jia

• , Albert C. Fahrenbach

• , Neha P. Kamat

• , Katarzyna P. Adamala

• […]

•  & Jack W. Szostak

• - Show fewer authors

• Nature Chemistry 9, 1286 (2017)

• doi:10.1038/nchem.2885

Published online:

23 November 2017

• Original article: 27 June 2016

Nature Chemistry 8, 915–921 (2016); published online 27 June 2016; retracted after print 12 October 2017.

We the authors are retracting this Article because our efforts to repeat and follow up on the results have been unsuccessful. Specifically, we have been unable to reproduce observations suggesting that arginine-rich peptides allow the non-enzymatic copying of an RNA template in the presence of its complementary strand (Fig. 4e). We originally dismissed variability in these experiments as resulting from variability in the snap cooling of samples following thermal denaturation. However, we now understand that the data reported in the published article are the result of false positives that arose from an incorrectly designed experiment in which random errors, including transfer and concentration errors, affected the ratio of the concentrations of the RNA template and its complementary strand. This resulted in false positives that were misinterpreted as template copying in the presence of a complementary strand, where in reality these reactions did not contain enough complementary strands to completely inhibit the reaction.

Subsequent experiments suggested that arginine-rich peptides may not slow the reannealing of complementary strands (Fig. 3), and that what we had previously interpreted as a decrease in annealing rate was actually an artefact due to slow coalescence or strand exchange between droplets of RNA–peptide coacervate, as well as droplet coalescence and settling that led to decreased fluorescence intensity. Similarly, the changing circular dichroism spectra shown in Figure 2c, which were originally interpreted to be the result of a change in the global helical structure of RNA upon peptide binding, may also be an artefact due to, for example, loss of signal or light scattering. Although the binding of arginine-rich peptides to RNA does form condensed-phase droplets, and although most of the RNA does reside within the condensed phase, follow-up experiments to confirm that non-enzymatic RNA polymerization occurs within these coacervate droplets have been inconclusive (Fig. 5d).

The experiments showing that vesicles are stable in the presence of arginine-rich peptides (Supplementary Figure 26, by N. Kamat), and the failure of acidic peptides to condense RNA (Supplementary Figure 8, by K. Adamala) have been reproduced. However, since the main conclusions of our paper are incorrect, all of the authors are now retracting the Article. The authors would like to thank Dr Tivoli Olsen for her extensive efforts to unravel the errors in our Article and we apologize to the scientific community for any confusion arising from our publication.

大家看到没有？原来一个诺奖得主也可以做这样的灰常严谨的科研：实验研究设计错误、有意去除变异、结果解读偏颇。因此，许多“false positives”（假阳性）的“artefact”（人造现象）被当作了新的科学发现。

真不知道同行评审灰常严格的《自然》牌杂志是怎么评审这个论文的，不会是一些评审专家一见是来自自世界名牌大学哈佛大学的研究、通讯作者还是一个诺奖得主就傻眼了吧？

更要命的是，这样一个伪科学发现的论文发表后还被引用了9次！真不知道这些引用是如何“赞美“这一伪大发现的？

《自然-化学》撤稿声明 的PDF 全文如下：