Nature trapped by flawed and fraud STAP cell papers

Nature trapped by flawed and fraud STAP cell papers

The following is an Open Letter that I sent to Nature on March 20th, 2014.  Its main content still remains valuable because Nature is still trapped by STAP cell papers even though it was forced to make some retractions.  Nature needs to open its review files on the STAP cell papers to clear its responsibility for promoting some pseudo-science.

Getting out of the STAP’s trap: an open letter to Nature

March 20th, 2014

Dear Nature Editor-in-Chief Dr. Campbell,

I am very sad that Nature is now trapped into a big mess formed by its high-profile publication of stimulus-triggered acquisition of pluripotency (STAP) cells.  I knew this so-called great discovery is a huge hype immediately after I scanned the “twin” research papers and the “duel” news articles on it.  Thus I post a blog article on the very same day Nature published these papers.  I also wished to write a Communication Arising to Nature but did not finish it because my frustration with repeated rejections by Nature on my many solid criticisms against Nature’s flawed publications.

However, if Nature was willing to listen to my points of views, my Communication Arising would be look like this at its beginning (copied from an earlier draft):

Earlier this year Nature published twin papers 1 describing a so-called breakthrough in stem cell research: a simple acid bath will create stem cells 2 with unchained potency 3. However, many attempts to replicate this stimulus-triggered acquisition of pluripotency (STAP) have been failed 4 and the twin papers are even under fire 5 with investigation 6 going on for some data problems 7. The provision of some essential technical tips for generating STAP cells 8 may help overcoming some replicating difficulties. But our analysis on the original papers and the subsequent tips suggests that the general claim of obtaining STAP cells with unchained potency from any tissues through a simple acid bath maybe a mere hype in nature.

Certainly Nature would be very unhappy to see my characterization of its cherished discovery as “a mere hype”.  But I am afraid my characterization would be too “mild” this time because the so-called discovery may even be proved as a major fraud.  Thus, I had asked Nature to retract these STAP papers in my another blog article before a coauthor of the papers expressed this desire.

In order for Nature to come out of this STAP mess “clean” I suggest Nature to investigate its publication process of these problematic papers.  Nature should open its reviewing process and all review comments to public so that scientific community as a whole can learn a serious lesson from this tragic incidence.

Many criticisms on the STAP papers have focused on image manipulation and text plagiarism in the publications of the leading author of the STAP papers.  I would direct your attention to some other problems.  These other problems may add more suspicions to the validity of the discoveries made by the leading researcher on the STAP cells.

On February 21st 2014 I performed a Pubmed search for papers containing author “Obokata, H.”.  I found following 9 publications matching the searching criterion:

  1. Obokata H, Sasai Y, Niwa H, Kadota M, Andrabi M, Takata N, et al. Bidirectional developmental potential in reprogrammed cells with acquired pluripotency. Nature. 2014;505(7485):676-80. Epub 2014/01/31.
  2. Obokata H, Wakayama T, Sasai Y, Kojima K, Vacanti MP, Niwa H, et al. Stimulus-triggered fate conversion of somatic cells into pluripotency. Nature. 2014;505(7485):641-7. Epub 2014/01/31.
  3. Wakayama S, Kohda T, Obokata H, Tokoro M, Li C, Terashita Y, et al. Successful serial recloning in the mouse over multiple generations. Cell stem cell. 2013;12(3):293-7. Epub 2013/03/12.
  4. Canseco JA, Kojima K, Penvose AR, Ross JD, Obokata H, Gomoll AH, et al. Effect on ligament marker expression by direct-contact co-culture of mesenchymal stem cells and anterior cruciate ligament cells. Tissue engineering Part A. 2012;18(23-24):2549-58. Epub 2012/07/12.
  5. Obokata H, Yamato M, Tsuneda S, Okano T. Reproducible subcutaneous transplantation of cell sheets into recipient mice. Nature protocols. 2011;6(7):1053-9. Epub 2011/07/02.
  6. Pirraco RP, Obokata H, Iwata T, Marques AP, Tsuneda S, Yamato M, et al. Development of osteogenic cell sheets for bone tissue engineering applications. Tissue engineering Part A. 2011;17(11-12):1507-15. Epub 2011/02/01.
  7. Obokata H, Kojima K, Westerman K, Yamato M, Okano T, Tsuneda S, et al. The potential of stem cells in adult tissues representative of the three germ layers. Tissue engineering Part A. 2011;17(5-6):607-15. Epub 2010/10/05.
  8. Aoi Y, Kinoshita T, Hata T, Ohta H, Obokata H, Tsuneda S. Hollow-fiber membrane chamber as a device for in situ environmental cultivation. Applied and environmental microbiology. 2009;75(11):3826-33. Epub 2009/03/31.
  9. Obokata H, Yamato M, Yang J, Nishida K, Tsuneda S, Okano T. Subcutaneous transplantation of autologous oral mucosal epithelial cell sheets fabricated on temperature-responsive culture dishes. Journal of biomedical materials research Part A. 2008;86(4):1088-96. Epub 2007/12/15.

Among these 9 papers Obokata played a leading role (as the first author) in 5 papers.  Thus, Obokata is indeed an inexperienced researcher and her short research experience is limited to the technical level of cultivating cell sheets.

Reading Obokata’s earlier publications it seems she had a tendency to over-emphasize her “success” and over-look her failure.  For example, she have described her “success” of cultivating and transplanting cell sheets even though these cell sheets were rejected at the end.  If I were Obokata I would not publish several “succesful” cultivation papers on fabricating cell sheets if I knew the transplantations of these cell sheets all ended with complete degeneration.

Another thing that struked me is a total lack of correct understnading to some scientific methodologies she have used.  For example, in a paper published in Applied and Environmental Microbiology (75:3826-33, 2009), it was repeated in many places that inoculations were made to give 0.1 to 0.5 cell per chamber, or 0.1 to 0.3 cell per chamber.  Using the exact words as shown in the paper (p3832 left column), “The microbial cells were inoculated with 0.1 to 0.5 cell per chamber in this experiment”. I had done many years of microbiological research.  I knew I could not grow a microbial culture from 0.1 to 0.5 cell per chamber because I simply could not inoculate a fraction of a cell.

Apparently, Obokata has not been strictly trained and lacks a comprehensive knowledge.  Thus, it is not surprise she could make some “amazing” discovery.  But the problem with the publication of the STAP papers is that the papers should have been strictly peer-reviewed and rigorously edited.  Then how could such as “simple” method not be easiloy replicated?

In my opinion, Nature has been carried away with its “success” of hyping on iPS cells.  But if Nature had accepted my solid criticism on Yamanaka’s unproven claim Nature might have avoid this even more streched claim.

Interestingly, dispite both STAP research papers may be retracted, one statement in the STAP cell article remains valid: “no study so far has proven that such pluripotent cells can arise from differentiated somatic cells”.  Even though Yamanaka was awarded a Nobel Prize for “the discovery that mature cells can be reprogrammed to become pluripotent”, his response to my Communication Arising to Nature (rejected by Nature but published in Logical Biology) should reflect the truth which is (in his words): “We have never claimed that we generated iPS cells from terminally differentiated cells”.

So what about the repeated hyping on reprograming mature somatic cells into embryonic stem cell-like pluripotent stem cells?  It is really a joke because embryonic stem cells are alive even in mature body and adult stem cells exist in many places in various tissues.  These cells can be selected out even without reprogramming.  But these cells can be changed with reprogramming and can even be changed into cancer cells by iPS reprogramming.

It is a high time for Nature to seriously think the risk of continuing a strong belief in cell DIVISION-based biology and the reward of embrasing a solid discovery on cell REPRODUCTION life science.  No cell can be DIVIDED to live and even “self-renew”.  All cells can REPRODUCE and become older.  This fundamental difference in the basic understanding of cell life may explain why CNS have kept publishing many flawed and even fraud papers while Logical Biology has no need to retract any of its publications.

By the way, I knew that you have received my recent two letters asking you to write to the non-responding “corresponding” authors of two other Nature papers to submit their data for my independent analysis.  I wish you could quickly do that so that some other mistakes promoted by Nature should not remain in nature for too long.

Sincerely,

Shi V. Liu MD PhD

Eagle Institute of Molecular Medicine

Apex, NC, USA

An Open Letter to CNS (Cell, Nature and Science)

An Open Letter to CNS (Cell, Nature and Science)
Valid Scientific Discoveries Should Not Be Neglected

Over the past two decades CNS (Cell, Nature and Science) has collectively engaged in rejecting my
insightful discoveries on cell life, neglecting my publications and suppression my right for criticizing
their mistaken publications. This Open Letter records some of the events and shows public the right
knowledge on life science over the deceptions in the top journals.

Click  HTM or PDF  to read full-length paper free of charge and leave your comment here.

 

 

 

 

刘实致信《自然》要求撤销美国哈佛大学一篇论文

刘实致信《自然》要求撤销美国哈佛大学一篇论文

英语原文及汉语译文

July 17, 2014

2014年7月17日

Dear Editor-in-Chief of Nature,

亲爱的《自然》主编,

I sent you an email recently complaining the intentional and repeated removals of my submissions, without (sending me) any decision on the submissions, from Nature’s manuscript tracking system. I have not received your response, as usually the case for my prior communications to you.

最近我发给您一封电子信抱怨不给我任何通知就有意多次将我的投稿从《自然》稿件处理系统去除。但我还没收到您的回复,就像过去我与您通讯的结果一样。

Now I just read a Retraction published in Nature (http://www.nature.com/nature/journal/v511/n7509/full/nature13549.html) which prompts me to write you this demand for retracting another Nature publication.

现在我刚读了《自然》的一个撤稿声明(http://www.nature.com/nature/journal/v511/n7509/full/nature13549.html),它促使我给您写这封信提出撤除另一篇《自然》论文的要求。

A recent research article in Nature [T. M. Norman, N. D. Lord, J. Paulsson, R. Losick, Nature 503, 481 (2013).] made a claim for bacterial differentiation by presenting a so-called “cell fate switching” between a motile unicellular state and a chained multicellular state in bacterium Bacillus subtilis.  This study was highlighted as “systems biology: how bacteria choose a lifestyle” [J. W. Locke, Nature 503, 476 (2013)].

最近《自然》发表的一篇研究长文[T. M. Norman, N. D. Lord, J. Paulsson, R. Losick, Nature 503, 481 (2013).]通过表现所谓的在枯草杆菌的游动单细胞状态和成链多细胞状态存在“细胞命运转变”而声称细菌分化。该文被高调誉为:“系统生物学:细菌如何选择生活方式” [J. W. Locke, Nature 503, 476 (2013)]。

However, after carefully reading this new research paper, I realized that the claim of “cell fate switching” is most likely an illusion derived from using incorrect study approach and making erroneous data manipulation based on some invalid assumptions.  Thus, I wrote my first letter to all authors including two corresponding authors, asking 10 initial questions.  I told them that their quick response would be very helpful for my further analysis on their paper.  Unfortunately, I did not receive any response, even after I sent more letters urging them living up to the corresponding authors’ responsibility.

然而,仔细阅读这篇研究论文后,我认识到所谓的“细胞命运转变”很可能是由于以一些错误假设为基础而采取错误的研究途径并进行了错误的数据处理而产生的幻觉。因此,我给论文的所有作者去信,提出10个初步问题。我告诉他们我需要他们的及时答复以便进一步分析。不幸的是,即使我多次去信催促他们履行通讯作者的责任,至今我还没收到他们的任何答复。

Thus, I made my analysis on their claims using information presented in their publication without access to the underlying data.  Even so I still could make some solid criticisms on their main conclusion: discovery of an autonomous “cell-fate” switching between a motile unicellular state and a chained multicellular state for bacterium Bacillus subtilis.

因此,我只能在无法接触他们所发论文的底层数据的情况下利用公开的信息对他们的声称进行分析。即便如此,我仍然能够对他们的主要结论— 枯草杆菌存在游动单细胞状态和成链多细胞状态之间的自发性“细胞命运”转变—做出一些扎实的批评。

I submitted my analysis as a Communications Arising to Nature.  Nature rejected it without requesting a peer review on it.  Nature also ignored my plea to it for asking the authors of their publication to give a response.

我将我的分析写成“辩论争鸣”投稿《自然》,然而却被《自然》不经同行评审就拒绝。《自然》也忽视了我提出的由它再要求其论文作者给予答复的请求。

The Nature-rejected Communications Arising was published in Logical Biology [13(1): 3-7, 2014] (see attached PDF)  and, as part of the evidence for identifying some potential misconduct, was sent to Harvard University’s Research Integrity Officer for Faculty of Arts and Sciences, Dr. Gearoid P. Griffin.  My complaint was received by on Feb. 5th, 2014 and also received by the Office of Research Integrity (ORI) on the same time.  You and Nature should also received copies of these communications as I usually put you on the CC list.

被《自然》拒绝的辩论争鸣文章后来在《逻辑生物学》发表 [13(1): 3-7, 2014] (见所附PDF文件),此文已作为识别一些可能的不端行为的证据的一部分提交给哈佛大学艺术与科学学院的研究伦理官Gearoid P. Griffin博士。我的抱怨是在2014年2月5日被他收到,同时也被研究诚信办公室(ORI)收到。而您和《自然》也应当收到,因为我通常也把您放在抄送名单里。

Now more than 5 months have passed.  I haven’t  received any decision from Harvard University with regarding my complaint.  But the incorrect interpretation and wrong conclusion made in the Nature publication should not be remained in scientific literature when the so-called “corresponding authors” even do not live up to an intrinsic responsibility of responding to scientific criticism.

如今5个多月过去了,我还未收到哈佛大学对此事的处理决定。但是,一个被错误解读和被错误结论的《自然》论文不应被保留在科学文献中,特别是当所谓的“通讯作者”甚至都不履行其本职责任回答科学批评的时候。

Thus, just as a wrongly interpreted publication not replicated by the authors needs to be retracted as shown in the recent retraction mentioned in the  beginning of this email, a mis-interpreted and erroneously concluded publication already solidly challenged by other scientist also needs to be retracted, unless the authors can offer convincing counter-arguments and invalidate the criticisms.

因此,正如本信开头提到的一个作者本身不能重复的被错误解读的论文会被撤稿一样,一个错误解读和错误结论并被其他科学家有力批驳的论文也应当被撤稿,除非作者能进行有效辩护并推翻批评。

Nature should learn a real lesson  from its heavy spin on the STAP cells.  One way to learn a real lesson is to open its door to solid scientific criticisms.  This should include stopping unjustified rejection of my submissions criticizing Nature’s flawed and even fraud publications and allowing me to log on to Nature’s website to make timely comment on Nature’s publication.

《自然》应当从它对“酸澡细胞”的大肆吹捧中得到真正的教训。一个吸取教训的办法就是对扎实的科学批评敞开它的大门。这应当包括停止对我批评《自然》有错甚至于有假的论文的投稿进行无理拒绝,也包括允许我登录《自然》网站对其发表文章进行及时评论。

If Nature wishes to reduce its chance of publishing too amazing and thus really unbelievable “discovery” /deception in biological field it may be even worthy of sending some “breakthrough” studies to me for a critical review before they break the trust of public to “science”.  My service to Nature in this respect will be totally free.  But I wish to be identified in real name and thus be held responsible for any of my reviews.

如果《自然》希望减少它在生物学领域发表太惊奇因此也真的不可信的“发现”/欺诈,或许有必要将一些“突破”性研究在发表前送我审阅以免它们打破大众对“科学”的信任。我对《自然》的这种服务是完全免费的。但有一个希望:我的所有评审都将以实名标出,以便将我文负其责。

Sincerely,

诚挚的,

Shi V. Liu MD PhD

刘实,医学博士和哲学博士

An Open Letter to Nature for demanding a retraction

Here is what I wrote to the Editor-in-Chief of Nature and now wish to share with public:

A demand for retraction of a Nature publication

July 17, 2014

Dear Editor-in-Chief of Nature,

I sent you an email recently complaining the intentional and repeated removals of my submissions, without (sending me) any decision on the submissions, from Nature’s manuscript tracking system. I have not received your response, as usually the case for my prior communications to you.
Now I just read a Retraction published in Nature (http://www.nature.com/nature/journal/v511/n7509/full/nature13549.html) which prompts me to write you this demand for retracting another Nature publication.
A recent research article in Nature [T. M. Norman, N. D. Lord, J. Paulsson, R. Losick, Nature 503, 481 (2013).] made a claim for bacterial differentiation by presenting a so-called “cell fate switching” between a motile unicellular state and a chained multicellular state in bacterium Bacillus subtilis. This study was highlighted as “systems biology: how bacteria choose a lifestyle” [J. W. Locke, Nature 503, 476 (2013)].
However, after carefully reading this new research paper, I realized that the claim of “cell fate switching” is most likely an illusion derived from using incorrect study approach and making erroneous data manipulation based on some invalid assumptions. Thus, I wrote my first letter to all authors including two corresponding authors, asking 10 initial questions. I told them that their quick response would be very helpful for my further analysis on their paper. Unfortunately, I did not receive any response, even after I sent more letters urging them living up to the corresponding authors’ responsibility.

Thus, I made my analysis on their claims using information presented in their publication without access to the underlying data. Even so I still could make some solid criticisms on their main conclusion: discovery of an autonomous “cell-fate” switching between a motile unicellular state and a chained multicellular state for bacterium Bacillus subtilis.

I submitted my analysis as a Communications Arising to Nature. Nature rejected it without requesting a peer review on it. Nature also ignored my plea to it for asking the authors of their publication to give a response.

The Nature-rejected Communications Arising was published in Logical Biology [13(1): 3-7, 2014] (see attached PDF) and, as part of the evidence for identifying some potential misconduct, was sent to Harvard University’s Research Integrity Officer for Faculty of Arts and Sciences, Dr. Gearoid P. Griffin. My complaint was received by on Feb. 5th, 2014 and also received by the Office of Research Integrity (ORI) on the same time. You and Nature should also received copies of these communications as I usually put you on the CC list.

Now more than 5 months have passed. I haven’t received any decision from Harvard University with regarding my complaint. But the incorrect interpretation and wrong conclusion made in the Nature publication should not be remained in scientific literature when the so-called “corresponding authors” even do not live up to an intrinsic responsibility of responding to scientific criticism.

Thus, just as a wrongly interpreted publication not replicated by the authors needs to be retracted as shown in the recent retraction mentioned in the beginning of this email, a mis-interpreted and erroneously concluded publication already solidly challenged by other scientist also needs to be retracted, unless the authors can offer convincing counter-arguments and invalidate the criticisms.

Nature should learn a real lesson from its heavy spin on the STAP cells. One way to learn a real lesson is to open its door to solid scientific criticisms. This should include stopping unjustified rejection of my submissions criticizing Nature’s flawed and even fraud publications and allowing me to log on to Nature’s website to make timely comment on Nature’s publication.

If Nature wishes to reduce its chance of publishing too amazing and thus really unbelievable “discovery” /deception in biological field it may be even worthy of sending some “breakthrough” studies to me for a critical review before they break the trust of public to “science”. My service to Nature in this respect will be totally free. But I wish to be identified in real name and thus be held responsible for any of my reviews.

Sincerely,

Shi V. Liu MD PhD

LB2014V13N1A2_CellFate.pdf