本帖最后由 FreeCell 于 2014-9-16 12:45 编辑
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* o! n: C8 O' `( c( E《自然》企图救赎STAP( x+ a+ H7 X6 ^( E" d! X
( @' w, S& @* s" [- `8 m2 @New details emerge on retracted STAP papers
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& g6 ~* u1 k/ h7 o; d8 } [6 v+ w11 Sep 2014 | 18:52 BST | Posted by Davide Castelvecchi | Category: Ethics, stem cells* p* p+ T! T: t" w
Posted on behalf of David Cyranoski.
, J# w) L7 K, l- L6 v8 W7 \New leaked e-mails showing the comments of referees for Science and Nature provide more insight into the saga of the STAP papers, which Nature published in January and retracted in July.
& ^% g) ?& L" y( a: X# RThe papers had promised new, simpler ways to produce stem cells by applying stress to cells taken from a patient’s tissues. But no other lab was able to reproduce the results, and experts pointed to several problems and inconsistencies in the papers. In April, first author Haruko Obokata of the RIKEN Center for Developmental Biology in Kobe, Japan, was declared guilty of scientific misconduct; the controversy later took a tragic turn as another co-author, Yoshiki Sasai, committed suicide on 5 August.' {! R9 b5 n: @& D4 ]3 `
An investigative report into the papers, released in May, revealed that a previous version of the work had been rejected by Nature, Cell and Science in 2012, before being resubmitted and accepted by Nature. (Nature’s news and comment team is editorially independent of its research editorial team.)# |: v& _5 f3 [
That report gave details from the Science referees who pointed out that one figure had been “reconstructed” in a way at odds with normal scientific practice and another one had a “suspiciously sharp” band (see ‘Misconduct verdict stands for Japanese stem-cell researcher‘).6 y) ?# t% O5 Z5 |" w
The blog Retraction Watch posted the full comments of three referees who reviewed the paper for Science on 10 September.
j& T$ |5 i. x& E& W/ \# hThe reviews include a modicum of support, but overall the paper was panned by all three. Reviewer 2 notes, “Unfortunately, the paper presents only a superficial description of many critical aspects of the work,” before launching into 21 points that “need to be addressed”, ranging from seemingly sloppy mistakes to fundamental problems with the data.
. F& Y% G$ K- A* z1 r) gReviewer 3 noted, “If these results are repeatable, a paradigm of developmental biology would be changed.”
8 P& H/ ?% o8 A. _# }- N9 wThe manuscript itself is not available, so it is impossible to know exactly how similar the rejected Science manuscript is to the version that was eventually published in Nature., p( @' q+ m1 ]2 u( K ^
When the committee initially brought the problems in the Science paper to her attention, Obokata defended herself by saying that the published Nature paper had main conclusions that differed from those in the rejected Science manuscript, and she refused to show the latter to the investigative committee., K3 M& L* t. \9 ?7 O, g8 \/ a
The cells in that manuscript were called stress-altered somatic cells (SAC) cells, whereas those in the paper that was eventually published bore the now-infamous name of the method: stimulus-triggered acquisition of pluripotency, or STAP. But judging from the reviewers’ comments, STAP cells and SAC cells seem to be very similar.4 U$ o" q# M9 N8 a4 L
Nature‘s research editors do not comment on their correspondence with authors, but on 11 September Science revealed new e-mails said to have been exchanged between Obokata and a Nature editor in April 2013. Those e-mails allegedly quote Nature‘s reviewers as having many reservations similar to those expressed by Science‘s reviewers, and unanimously recommending that the paper be rejected — which Nature did. The Nature editor did leave open the possibility of publishing the paper if the problems were solved. About 9 months later, in December, Nature accepted both papers.; m4 p4 J, r7 m3 f4 p8 R
u: B q0 {0 H& Z# a eSTAP co-author offers yet another recipe for stem cells : Q1 c+ k. H+ F1 r$ R: _4 l. V& W' O
12 Sep 2014 | 22:28 BST | Posted by David Cyranoski | Category: Lab life, stem cells
* [. S# C* g' b" CA senior co-author on controversial, and now retracted, stem cell papers has quietly posted new tips on how the research can be replicated.
% F5 H( Y3 u) _3 |7 h4 | M: G+ CTwo papers claiming that stressing the body’s cell could produce embryonic-like stem cells, a process called stimulus triggered acquisition of pluripotency (STAP), were heralded when published in Nature in January but thrashed soon after when problematic images and figures were soon found.
B) W6 z$ c4 M3 dThat might not have been so worrisome if the experiments, which the authors called easy to do, were replicated, but various external groups tried and failed to do so. Co-authors in Japan responded with a tip sheet. Soon after that, the lead author on the paper laying out the fundamental STAP technology, Charles Vacanti of the Brigham and Women’s Hospital in Boston, Massachusetts, released his own, quite different, list of tips for reproducing STAP. Still no one succeeded in replicating the findings." u b1 m9 s% ?- q$ |, m
Since April, Hitoshi Niwa, a well-respected mouse-stem-cell specialist at the RIKEN Center for Developmental Biology (CDB) in Kobe and a co-author on the papers, has been giving a focused, last-ditch effort to replicate the experiment; on 27 August, he reported no luck so far and suggested that light emission from dying cells, known as autofluorescence, might have been confused with fluorescent tags meant to signal conversion to the embryonic-like state.
8 p7 j! U6 V. e# p2 \$ x1 {During that period, the lead author on both papers, the CDB’s Haruko Obokata, was found guilty of misconduct and both papers were retracted. Obokata’s supervisor at the CDB, Yoshiki Sasai, committed suicide, and Vacanti stepped down as chairman of Brigham and Women’s department of anaesthesiology, perioperative and pain medicine. The CDB itself has halved in size." j' X5 k2 I) a" f
One might have thought that STAP was finished. But Vacanti is not one to give up so easily.
; p! Y" @% j# ^Even when he finally agreed to retract the papers, he maintained, in a post on his department’s website, that “there has been no information that cast doubt on the existence of the stimulus-triggered acquisition of pluripotency (STAP) cell phenomenon itself.” Vacanti said that he was confident that Niwa would “replicate the core STAP cell concept that my brother Martin and I originally hypothesized, and trust that it will be verified by the RIKEN as well as independently by others.”2 V9 l+ R- s9 X" S/ j
Now, in a note posted without fanfare on Vacanti’s department’s website and dated 3 September — one week after Niwa announced failure to replicate the findings — Vacanti has offered his second revision to the STAP protocol.8 W/ w2 y0 E1 y9 ?+ M: R, y
In comparison his first revised protocol in March (‘Refined protocol for generating STAP cells from mature somatic cells’), the new one (‘REVISED STAP CELL PROTOCOL. 09.03.14′) highlights the use of ATP in the solution, in combination with two stresses — exposure to acid and physical pressure on the cell membranes — that he used in the previous recipe. “In recent months, our lab decided to re-explore the utility of a low pH solution containing ATP in generating STAP cells,” Vacanti writes in the revised protocol. “We found that while pH alone resulted in the generation of STAP cells, the use of a low pH solution containing ATP, dramatically increased the efficacy of this conversion. When this acidic ATP solution was used in combination with mechanical trituration of mature cells, the results were even more profound” (emphasis original).
$ n) j+ @+ a2 @“We made a significant mistake in our original declaration that the protocol was ‘easy’ to repeat,” the protocol continues. “This was our belief at the time, but it turned out to be incorrect. Many of the steps described appear to be a function of the technique of the individual investigator. Consequently, the revised protocol below should increase the likelihood of success.” |
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发表于 2014-9-14 14:55
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