潤濤閻 (熱門博主)
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(2020-07-05 16:47:36) 下一個


這是經過了一年多與貴刊打交道後到目前為止的最新進展。雖然雜誌的《評論》是讀者自己注冊後便可貼上去的,但我的評論需要經過編輯審查。我隻能投訴顏寧博士沒引用我們的論文,因為負責此事的資深編輯認為我們的論文應該被引用。其它方麵,他說由於顏寧的論文是受到了同行審查的,我可以貼論文裏的哪些缺陷,但不能有misconduct/fool the readers/misleading the scientifc community 等字眼,否則當即被刪除。事實上,有這類指控內容的,我都貼不上,因為給我設計了專門的隻要我 log in 就消失了“發送”鍵的頁麵。


那麽,我就可以把此信在網絡上公開了。因為總有網友提議要把英文版貼出來,知道我質疑顏寧論文造假/欺騙的內容是什麽。畢竟這一科學發現被列為“十大科學進展”,也令顏寧博士獲得了貴校終身冠名講席教授的職位、美國科學院院士稱號,也獲得了中華人民共和國百萬元級別的科學榮譽獎“Seek Truth Award”(中文:求是獎)。

我把此信附在下麵。《自然》雜誌下麵的評論欄裏也有,我本來是貼在2014論文下麵的,是資深編輯看了後建議質疑哪篇的就分開貼在哪篇的評論裏。下麵的版本是我的質疑信,分開貼在了《自然》雜誌2014 和 2015 兩篇論文的下麵評論欄目裏。



我不知道誰是顏寧論文的審稿人,但我知道中國國內媒體當年公開發表了三位美國著名科學家對顏寧論文的高度評價,都是美國科學院院士,有一位諾貝爾獎得主。顯然,他們是看過顏寧2014年發表的葡萄糖載體(她稱之為轉運蛋白)論文的。載體和轉運蛋白,也是從英文翻譯過來的,一個是carrier, 一個是transporter,至今二者通用。



Dear Nature,

I am writing to you with a concern about Dr. Nieng Yan, a Member of the U.S. National Academy of Sciences (NAS). I believe she is guilty of scientific misconduct, and I have evidence to prove it.

1.Misleading the scientific community—-“latch gate” theory

In the paper, she identified an “latch” which was one of her two main findings, and she thoroughly explained her latch gate finding (the other main finding was “the Glut1 working model”).

In Fig.3 and Fig. 5, she named it an ICH domain and explained the ICH domain function as: “The ICH domain serves as a latch that tightens the intracellular gate.”(p.123) “Because of the extensive interactions between TMD and ICH, the ligand-free protein may prefer an outward-open conformation.” (p.124)

In fact, the XylE and Glut1 are transporters belonging to the Facilitated Diffusion Superfamily, whose function (direction and efficiency) solely depends on the substrate concentration gradient across the membrane, and functionally no sided-ness. This means the glucose can be transported from one side of the membrane to the other and vice versa. It is impossible for a “facilitated diffusion transporter” to have a “LATCH GATE” to maintain the out-facing direction.  If so, they are no longer “Diffusion Transporters.”  Instead, they are “GATED CHANNELS.”

If Dr. Nieng Yan’s “outward-open latch” theory was true, then the glucose transporters COULD NOT RELEASE accumulated glucose into the extracellular space adjacent to the blood capillary, because the “Latch Gate” would make the transporter bear outward-open conformation with the inside closed by the latch, so that the glucose inside could not get into the translocation pathway of the transporter.

In nature, glucose transporters DO release accumulated glucose into the extracellular space adjacent to the blood capillary by facilitated diffusion.

In addition, if the latch had no function, then it should have been eliminated during the 3 billion years of transporter evolution.

Apparently, Dr. Nieng Yan never did a biochemical assay for any Facilitated Diffusion Superfamily transporters and merely assumed that the glucose was transported only from outside to inside of the cells, and that the glucose concentration inside was always lower than outside, thus devising an artificial “outward-open conformation latch gate” theory without any scientific data to support it. The reviewers should have caught that, because in the paper, she mentioned that the XylE and Glut1 are members of the facilitated diffusion superfamily.

She found the ICH latch domain from a crystallized symporter (XylE), and she predicted that “substrate-free uniporters have a preferred open conformation” (P.124), which means that all of the uniporters should no longer be “Facilitated Diffusion Superfamily” members.

How can such an illogical and unrealistic “theory”, without any biochemical analysis or any scientific data support, be accepted by Nature reviewers, thus misleading the scientific community?

I don’t know the answer. However, if I were to guess, I can imagine two possibilities.  (A) Some reviewers may not be in the transporter field and have never done any biochemical assay in order to know that the facilitated diffusion transporters functionally have no sidedness, and therefore these reviewers just trusted Dr Nieng Yan. (B). A reviewer might have been in the transporter field,  and perhaps, this reviewer might have been reluctant to challenge Dr. Nieng Yan’s scientific work, due to fear of losing funding from the  Chinese government by collaboration.  

2.Fooling the scientific community

The “four conformational structures” described in the paper to prove her major scientific contribution cannot prove the working model. When the transporter (also called carrier) was in occluded inward-facing conformation (which means a glucose molecule was inside the transporter), Dr. Nieng Yan presented it as evidence that the glucose had entered the transporter from inside the cell (see Fig 5). However, the glucose could have been transported from outside the cell during crystallization. That is why we have to use radioactive labeled substrates in our experiments  [Runtao Yan & Peter C Maloney (JHU),1993 Cell, 75:37-44; 1995 PNAS, 92:5973-5976].

A simple example can illustrate this point. Suppose I show a picture of a man on a boat on the north bank of a river, and then assert that the man had boarded the boat from the north bank, a skeptic could question my inference, since the man might have ferried from the south to the north bank.

Does this represent Dr. Nieng Yan’s level of logical thinking, or is she being deliberately deceptive? She should know that her “four conformational structures” cannot prove the working model of a transporter. How could she possibly ascertain whether the glucose was from the inside the cell, or transported from outside? It would be impossible for her to distinguish without radioactively labeling the substrate.

3.Deceiving and fabricating

Even if the “four-conformation structures” proposed in the paper could prove that to be the working model of a transporter (which, in fact it could not), Dr. Nieng Yan did not find the four structures. In her paper, she claimed that the four structures are required for a complete transport cycle. However, there are only two crystal structures of E. coli xylose transporter (proton co-transporter, i.e. symporter), and one human glucose transporter Glut-1(uniporter). Even after combining the symporter and uniporter together, she only obtained THREE structures. When she presented “A working model of Glut1” (written in bold-faced typesetting) from Fig. 5, her conclusion was based on the “Predicted data” from Fig 5’s detailed descriptions (written in small typeset). In other words, her work should be presented as a “Predicted working model of Glut1” instead of an actual “working model of Glut1”. The essence of this wording is deceptive.

It is impossible for Dr. Nieng Yan to propose a working model for Glut1 while lacking the basic experimentation of the “four conformation structure” cycle.   She clearly stated in her paper that (1) “the conformational switch from inward-facing to outward-facing of symporters remains to be elucidated”; and (2) The outward-open structure remains to be captured. 

4.Did not disclose the source of the “published biochemical data”

Since she did not obtain four crystal structures and had no way to identify the working model based on only three structures, she tried to fix the problem by providing more “evidence” in her discussion section, where she said, “On the basis of our structural analysis and published biochemical data, we propose a working model for Glut1” (P124 ). If she thought she did not need to provide appropriate references because the biochemical experiments were done in her lab, then she should not have used the term “Predicted” in Fig.5.

No matter who may ultimately have performed the experiment, the fact is that the cystine-scan method created by RuntaoYan/Peter C Maloney was the only biochemical method to identify the membrane transport working model (1995 PNAS, 92:5973-5976).

5.Deceiving her colleagues in 2015 Nature paper

Dr. Nieng Yan also deceived her scientific colleagues when she wrote in her 2015 Nature paper (Nature 526, 391–396) that occluded inward-facing conformation was the evidence that a glucose molecule inside the carrier had entered from the inside of the cell, and occluded outward-facing conformation was the evidence that the glucose molecule must have entered from outside the cell. She should have known better, with a background of having studied transporters. To return to my earlier boating illustration, if there is no ticket to check, how could you know where the man boarded?   (Just like if you do not use radioactive labeling!)

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閱讀 ()評論 (13)
ans 回複 悄悄話 這麽久了,正經搞這行的有人理你嗎?
聽說過永動機吧?你說你造出了永動機,會有人理你嗎?民工說1+1他早就會算,陳景潤是剽竊他的。 ????
舊日雲中守 回複 悄悄話 https://www.nature.com/articles/nature13306



‘直達快車’ https://disqus.com/by/runtaoyan/
雨女 回複 悄悄話 你看到付向東和楊輝事件了嗎?https://www.wenxuecity.com/news/2020/07/13/9657310.html
笑林 回複 悄悄話 施一公與閻潤濤在約翰霍普金斯大學同一院校分別讀博士,做博士後。顏寧是施一公的學生,後來又一起在清華大學做事。可以肯定施熟悉閻的研究成果,施也清楚顏的文章。我估計施不可能與這個事件無關。施很有可能是顏文章的幕後推手。
mafanda 回複 悄悄話 Nieng Yan?
Ning Yan?
Dalidali 回複 悄悄話 回複 '潤濤閻' 的評論 :
支持閻先生真名實姓打假!但非常難,非常難!尤其在中國目前這種風氣下! 我詢問過國內一位在分子生物學領域的”大牛“! 他說,這種事多了,沒時間關注和參與,但他顯然知道這件事!


潤濤閻 回複 悄悄話 如果科學領域也容忍造假欺騙,那西方科學界建立起來的二百多年的互信機製將蕩然無存,現代社會文明將走向滅亡。科學就是科學,與政治、國籍、立場、黨派毫無關係,即使燒死布魯諾,照樣改變不了地球圍繞太陽的事實。這是科學本身的尊嚴,也是科學的傲慢之所在。在短時間內,真理可以敗給強權,但人類曆史表明:真理最終戰勝強權。我們每個人都有義務為真理而戰。
潤濤閻 回複 悄悄話 回複 'bjszh' 的評論 :


bjszh 回複 悄悄話 “a ICH” ------ 我不懂專業,但這裏似乎應該是 an ICH。對不起,無意打擾,隻是覺得這樣級別的刊物上最好沒有TYPO。
潤濤閻 回複 悄悄話 回複 '愛吃麻辣燙' 的評論 :

愛吃麻辣燙 回複 悄悄話 回複 'undefined' 的評論 : Pubpeer也貼一份吧,很多人在Chrome上安裝了pubpeer的插件,這樣每次搜索那篇文獻,pubpeer插件都會提醒,這篇文章有同行討論和質疑。
潤濤閻 回複 悄悄話 回複 '愛吃麻辣燙' 的評論 :

愛吃麻辣燙 回複 悄悄話 貼在nature評論下麵,還不如貼到pubpeer上,你可以實名在上麵貼評論。