STAP細胞論文のサイエンスおよびネイチャー投稿時の査読コメント全文が公開

STAP細胞論文は笹井氏が共同著者として加わる以前にはサイエンスに投稿され却下されていました。笹井氏が研究チームに加わり、論文執筆を主導してネイチャーに投稿したときもレフェリー(論文査読者)らは厳しい指摘をしていましたが、複数の改訂を経て最終的に受理されたといういきさつがあります。

STAP細胞論文を却下したサイエンス、およびネイチャーの査読者のコメントの全文がインターネット上で公開されています。通常、論文の査読はCONFIDENTIALであり、査読者のコメントがこのような形で世に出るというのは非常に異例なことです。

サイエンスへ投稿されたときの査読内容(全文へのリンク retractionwatch.comウェブサイト内)
論文タイトル:Stress altered somatic cells capable of forming an embryo
時期:2012年8月21日

Reviewer 1: ” … This is such an extraordinary claim that a very high level of proof is required to sustain it and I do not think this level has been reached. I suspect that the results are artifacts derived from the following processes: (1) the tendency of cells with GFP reporters to go green as they are dying. (2) the ease of cross contamination of cell lines kept in the same lab. …”

Reviewer 2: ” … Unfortunately, the paper presents only a superficial description of many critical aspects of the work. …”

Reviewer 3: “… If these results are repeatable, a paradigm of developmental biology would be changed. …”

特にサイエンスのレビューアー#1の人は、この論文の実験結果はアーチファクトの可能性が高く、データも矛盾に満ちたものであることを、非常に強い調子で指摘しています。

”The DNA analysis of the chimeric mice is the only piece of data that does not fit with the contamination theory. But the DNA fragments in the chimeras don’t look the same as those in the lymphocytes. This assay is not properly explained. If it is just an agarose gel then the small bands could be anything. Moreover this figure has been reconstructed. It is normal practice to insert thin white lines between lanes taken from different gels (lanes 3 and 6 are spliced in). Also I find the leading edge of the GL band suspiciously sharp in #2-#5.”

小保方晴子氏が理研でユニットリーダーになるための面接があったのが2012年12月21日で、このとき笹井芳樹氏は初めて小保方氏の研究内容を知り、竹市センター長の依頼を受けて論文の作成を支援することになりました。

笹井氏はネイチャー誌アーティクル論文の執筆指導を行い、小保方氏と共同でたたき台を2012年12 月28 日に完成、翌2013年1月にはバカンティ教授を訪ねて、さらに投稿原稿の検討を重ねました。同時に、レター論文のほうの執筆も進めました。2013年3月1日に小保方氏がユニットリーダーに着任。

2013年3月10日に、小保方氏を筆頭著者とする2報のSTAP細胞論文がネイチャーに投稿されました。

ネイチャーへ投稿された論文の査読内容(http://news.sciencemag.org/sites/default/files/NATURE%20REVIEWS.pdf
論文「Stimulus-Triggered Fate Conversion of Somatic Cells into Pluripotency」に対する査読者のコメント(2013年4月4日)

Referee #1: ” … This is a very interesting manuscript and potentially groundbraking. However, the presentation and data supporting the conclusions are somewhat speculative and, in some cases, preliminary. …”

Refree #2: ” … Most convincing, however, would be to demonstrate visually by time lapse tracking of single cells conversion of CD45 immunofluorescent cells into CD45 negative/Oct4 GFP positive cells that can also be stained with Ecadherin and/or Nanog. …”

Refree #3: “… the claim that these cells are pluripotent is not fully validated. The possibility remains that the tissues formed in vitro or in teratomas or chimeras are derived from multiple (perhaps partially ) reprogrammed cells, each with limited differetiation capacity. The authors might take advantage of the fact that some of the reprogrammed cells have T-cell receptor rearrangements to elucidate whether the differentiated cells in teratomas or mice are clonally derived. …”

NATUREに同時に投稿されたレター論文「Developmental potential for embryonic and placental lineages in reprogrammed cells with acquired pluripotency」に対する査読者のコメント(2013年4月4日)

Referee #1: ” .. it is important to realize not single experimetn in any of the two manuscript evaluates the “quality” of the cells, performs comparative genome-wide analysis or precise quantifiable assays side-by-side with ESCs/iPSCs. ..”

Referee #2: “. .. they do not decisively illuminate the identity of STAP cells. …”

Referee #3: ” … It is important to report the properties of clonally derived STAP ES like stem cells, otherwise, it is not clear whter one cell population gives rise to all the lineages in teratomas or in chimeras. …”

ネイチャーの3人の査読者らは論文の難点を指摘していますが、ネイチャー編集者の反応は非常に好意的なものでした。

“While they find your work of great potential interest, as do we, they have raised important concerns that in our view need to be addressed before we can consider publication in Nautre. Should further experimental data allow you to address these criticisms, we would be happy to look at a revised manuscript (unless something similar has been accepted at Nature or appeared elsewhere in the meantime). …””

この後、2回の改訂を経て最終的にネイチャーに受理されたようです。

Obokata et al., Stimulus-triggered fate conversion of somatic cells into pluripotency. Nature 505, 641–647  (30 January 2014)
Obokata et al., Bidirectional developmental potential in reprogrammed cells with acquired pluripotency. Nature 505, 676–680  (30 January 2014)
Received 10 March 2013
Accepted 20 December 2013
Published online 29 January 2014
Retraction (July, 2014)

参考

  1. Nature reviewers not persuaded by initial STAP stem cell papers (ScienceInsider
    Breaking news and analysis from the world of science policy 11 September 2014)
  2. “Potentially groundbreaking,” “highly provocative:” Nature STAP stem cell peer reviews published (retractionwatch.com)
  3. “Magical” STAP papers were blistered by Nature’s own reviewers, but then accepted just months later (Knoepfler Lab Stem Cell Blog September 11, 2014)
  4. CDB 自己点検の検証について(CDB 自己点検検証委員会 平成26 年6 月10 日)
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