“GSK中國(guó)研發(fā)總裁臧敬五論文造假事件”可能涉嫌內(nèi)部斗爭(zhēng)惡意抹黑

GSK全球副總裁，中國(guó)研發(fā)中心總裁臧敬五博士攝影/項(xiàng)軍強(qiáng)

5月31日，《新語(yǔ)絲》網(wǎng)站爆料，GSK中心研發(fā)中心總裁臧敬五《Nature Medicine》論文造假東窗事發(fā)己經(jīng)離職。

根 據(jù)這篇匿名爆料文章稱，臧敬五2010年發(fā)表在國(guó)際頂尖雜志《NatureMedicine》上的論文涉嫌造假，己離開(kāi)該公司并正在接受調(diào)查。該文（Nature Medicine2010,16:191-197）的第一、二作者是劉學(xué)彬（Xuebin Liu）、梁紹勤（StewartLeung），通迅作者是臧敬五（Jingwu ZZhang）。據(jù)該文報(bào)道，白細(xì)胞介素7（IL7）對(duì)多發(fā)性硬化癥動(dòng)物模型和患者血液中TH17細(xì)胞的生存和擴(kuò)增起關(guān)鍵作用，且阻斷IL7受體能減輕實(shí)驗(yàn)性多發(fā)性硬化癥動(dòng)物模型的病理變化和臨床體征。因此，IL7受體抗體己成為GSK治療多發(fā)性硬化癥的候選藥物并進(jìn)入臨床試驗(yàn)，被臧敬五樹(shù)為GSK中國(guó)研發(fā)中心的標(biāo)桿。接到舉報(bào)后，《NatureMedicine》和葛蘭素史克總部經(jīng)過(guò)慎重調(diào)查，在發(fā)現(xiàn)事實(shí)與舉報(bào)一致的情況下聯(lián)合派出調(diào)查組于2013年5月23日來(lái)到上海葛蘭素史克中國(guó)研發(fā)中心對(duì)該文主要作者臧敬五、劉學(xué)彬、梁紹勤等人進(jìn)行了單獨(dú)詢問(wèn)、核查。

然而，除了新語(yǔ)絲網(wǎng)站這篇匿名爆料文章，還有第二消息源確認(rèn)么?據(jù) 生物360網(wǎng)站編輯檢索，目前尚無(wú)該消息的英文報(bào)道來(lái)源。而且IL-7對(duì)多發(fā)性硬化癥的作用，被多個(gè)實(shí)驗(yàn)室重復(fù)出來(lái)，且目前多項(xiàng)研究都是建立在此項(xiàng)工作之上。這很有可能是對(duì)臧敬五的誣陷。

此外，作為一個(gè)企業(yè)有競(jìng)爭(zhēng)的，有競(jìng)爭(zhēng)就會(huì)有斗爭(zhēng)。很多事情都不是看起來(lái)那么簡(jiǎn)單，在事情沒(méi)有真相大白之前，誰(shuí)都不能妄下結(jié)論，尤其是此類涉及到個(gè)人聲譽(yù)的事情！據(jù)了解，臧敬五向來(lái)治學(xué)嚴(yán)謹(jǐn)，科研見(jiàn)解極深，深受學(xué)生及工作人員的敬愛(ài)，而且作為一個(gè)中國(guó)人走到今天的位置確實(shí)不易，單槍匹馬為了科學(xué)追求在海外奮斗。

觀察這篇爆料文章（詳見(jiàn)下文）的寫(xiě)作手法，作者可能是前GSK人員，應(yīng)該是與臧敬五等人有些“過(guò)節(jié)”。由此事件，筆者想到了某些人“見(jiàn)不得別人好”的劣根性，也希望不要借打假的名義冤枉好人。此次所謂的“造假事件”不希望為真，但愿以內(nèi)部斗爭(zhēng)失利了結(jié)。

另外，此次事件的爆出，筆者希望不要因?yàn)椤耙患核嚼钡哪涿隙绊懻麄€(gè)中國(guó)生物醫(yī)藥行業(yè)在世界的形象，更加不要影響到對(duì)中國(guó)R&D的投資。

臧敬五博士

臧敬五，神經(jīng)學(xué)專家，免疫和神經(jīng)退行性病變領(lǐng)域的科學(xué)家，目前擔(dān)任GSK中國(guó)研發(fā)中心總裁，主要開(kāi)展研究及新藥開(kāi)發(fā)和人員招聘工作。

在接受GSK任命之前，臧博士是位于上海健康科學(xué)研究所的創(chuàng)始人、所長(zhǎng)和教授。該所是中國(guó)科學(xué)院上海生命科學(xué)研究院和上海交通大學(xué)醫(yī)學(xué)院的聯(lián)合組建的轉(zhuǎn)化型醫(yī)學(xué)研究機(jī)構(gòu)。

臧博士曾就職與于美國(guó)德州休斯頓的Baylor醫(yī)學(xué)院，擔(dān)任Baylor多發(fā)性硬化癥中心的研究主任，負(fù)責(zé)多發(fā)性硬化和神經(jīng)免疫疾病的臨床研究工作。

臧博士畢業(yè)于上海第二醫(yī)科大學(xué)（現(xiàn)上海交通大學(xué)）臨床醫(yī)學(xué)專業(yè)，獲得比利時(shí)布魯塞爾大學(xué)免疫學(xué)博士學(xué)位并開(kāi)始涉足多發(fā)性硬化的研究。隨后，他在美國(guó)哈佛醫(yī)學(xué)院完成博士后研究工作，并在Baylor醫(yī)學(xué)院完成住院醫(yī)生訓(xùn)練。臧博士獲得Baylor醫(yī)學(xué)院神經(jīng)學(xué)教授職位，并持有美國(guó)德州和上海的行醫(yī)執(zhí)照?；貒?guó)工作后，在中國(guó)科學(xué)院和上海交通大學(xué)任職。他在轉(zhuǎn)化型轉(zhuǎn)換研究領(lǐng)域有20多年的經(jīng)驗(yàn)，發(fā)表過(guò)100多篇學(xué)術(shù)論文、綜述及專著。

爆料原文：

GSK中心研發(fā)中心總裁藏敬五Nature Medicine論文造假東窗事發(fā)己經(jīng)離職

作者：formergskemployees

據(jù) 悉， 葛蘭素史克中國(guó)研發(fā)中心（GlaxoSmithKline R&DChina)負(fù)責(zé)人臧敬五2010年發(fā)表在國(guó)際頂尖雜志NatureMedicine上的論文涉嫌造假，己離開(kāi)該公司并正在接受調(diào)查。該文（Nature Medicine2010,16:191-197）的第一、二作者是劉學(xué)彬（Xuebin Liu）、梁紹勤（StewartLeung），通迅作者是臧敬五。據(jù)該文報(bào)道，白細(xì)胞介素7（IL7）對(duì)多發(fā)性硬化癥動(dòng)物模型和患者血液中TH17細(xì)胞的生存和擴(kuò)增起關(guān)鍵作用，且阻斷IL7受體能減輕實(shí)驗(yàn)性多發(fā)性硬化癥動(dòng)物模型的病理變化和臨床體征。因此，IL7受體抗體己成為GSK治療多發(fā)性硬化癥的候選藥物并進(jìn)入臨床試驗(yàn)，被臧敬五樹(shù)為GSK中國(guó)研發(fā)中心的標(biāo)桿。

接到舉報(bào)后，Nature Medicine和葛蘭素史克總部經(jīng)過(guò)慎重調(diào)查，在發(fā)現(xiàn)事實(shí)與舉報(bào)一致的情況下聯(lián)合派出調(diào)查組于2013年5月23日來(lái)到上海葛蘭素史克中國(guó)研發(fā)中心對(duì)該文主要作者臧敬五、劉學(xué)彬、梁紹勤等人進(jìn)行了單獨(dú)詢問(wèn)、核查。臧敬五等人偽造實(shí)驗(yàn)結(jié)果的事實(shí)逐漸浮出水面。

1. 文中圖6（Figure 6）有關(guān)的IL7和IL7受體拮抗劑對(duì)多發(fā)性硬化癥患者血液中TH17細(xì)胞的生存和擴(kuò)增的實(shí)驗(yàn)結(jié)果純屬偽造！該圖中所有結(jié)果均來(lái)自于健康人而非多發(fā)性硬化癥患者血樣。調(diào)查組找出了圖6的原始實(shí)驗(yàn)記錄，上面明確寫(xiě)道實(shí)驗(yàn)結(jié)果來(lái)自于健康人血液樣品。在事實(shí)面前，劉學(xué)彬、梁紹勤、臧敬五無(wú)法抵賴,只有承認(rèn)圖6中的實(shí)驗(yàn)數(shù)據(jù)來(lái)自健康人，而不是文中多處（摘要、實(shí)驗(yàn)方法、結(jié)果、討論部分）所謂的來(lái)自于多發(fā)性硬化癥患者的血樣。為什么要用從健康人血樣中獲得的實(shí)驗(yàn)數(shù)據(jù)冒充是來(lái)自于多發(fā)性硬化癥患者血樣呢？難道是作者標(biāo)記錯(cuò)誤嗎？其實(shí)這里面大有玄機(jī)。原來(lái)，由于在中國(guó)無(wú)法收集到多發(fā)性硬化癥患者血樣（中國(guó)是該病低發(fā)地區(qū)），臧敬五遂與美國(guó)貝勒醫(yī)學(xué)院簽了一份合作協(xié)議，由時(shí)任貝勒醫(yī)學(xué)院助理教授的洪建負(fù)責(zé)收集多發(fā)性硬化癥患者血樣并完成實(shí)驗(yàn)。洪建用所收集到的極少數(shù)患者血樣進(jìn)行了實(shí)驗(yàn)，發(fā)現(xiàn)IL7拮抗劑并不能有效抑制TH17細(xì)胞。劉學(xué)彬、梁紹勤、臧敬五等人收到這一結(jié)果非常失望，于是找來(lái)健康人血樣，讓王春霞做實(shí)驗(yàn)得到了所謂的IL7拮抗劑抑制TH17的結(jié)果，然后偷梁換柱，謊稱是從多發(fā)性硬化癥患者血樣中獲得的數(shù)據(jù)。殊不知GSK對(duì)實(shí)驗(yàn)記錄有嚴(yán)格的管理措施，所有原始實(shí)驗(yàn)都記錄在電子記錄本（electronic labnotebook, eLNB）里，保存至少60年，且任何更改都會(huì)留記錄。因此調(diào)查組并未費(fèi)多少功夫便確認(rèn)其造假的事實(shí)。調(diào)查組還發(fā)現(xiàn)，論文投稿時(shí)間居然早于合作協(xié)議簽署時(shí)間！可見(jiàn)合作研究尚未正式啟動(dòng)而其實(shí)驗(yàn)結(jié)果已有了，而且論文已經(jīng)投稿了！GSK明文規(guī)定不允許在沒(méi)有有效協(xié)議的情況下與外單位合作，故此事也觸犯了GSK的Compliance 方面的規(guī)定。

2. 在該文附加圖7（supplementary 7）中，作者描述了IL7促進(jìn)MS患者血液中分化的TH17細(xì)胞中IL17的表達(dá)（?n?=?20?）。圖中20個(gè)點(diǎn)代表20個(gè)患者血樣。作者真的是從20例患者血樣中獲得的數(shù)據(jù)嗎？回答是否定的。據(jù)悉，他們僅做了極少數(shù)幾例，然后灌水，謊稱結(jié)果來(lái)自于20例患者血樣！可見(jiàn)附加圖7中的實(shí)驗(yàn)結(jié)果純屬偽造！有趣的是附加圖7上顯示的統(tǒng)計(jì)學(xué)結(jié)果是p<0.001, 而在第196頁(yè)＂結(jié)果＂部分，作者描述為 "Furthermore, invitro exposure of differentiated TH17 cells to IL-7 led tosignificantly increased production of IL-17 （n=20,P<0.01）"。同一結(jié)果，一處是p＜0.001, 而另一處是p<0.01，可見(jiàn)作者在偽造結(jié)果時(shí)多么不小心！

3.文中其它部分的實(shí)驗(yàn)結(jié)果是從多發(fā)性硬化癥小鼠模型中獲得的。雖然結(jié)果看似完美，但無(wú)法被輝瑞公司所重復(fù)！這已是業(yè)內(nèi)公開(kāi)的秘密。我們不禁要問(wèn)該實(shí)驗(yàn)的主要執(zhí)行者趙永剛同志，你心里踏實(shí)嗎？

4.論文是2010年發(fā)表的，到2013年被調(diào)查，這三年間臧敬五對(duì)以上造假的事實(shí)是否知情？從得知被調(diào)查之日起他的所作所為可見(jiàn)一斑。臧敬五于5月22日接到上級(jí)通知，讓他本人和該文的主要作者劉學(xué)彬和梁紹勤以及主要人血樣品實(shí)驗(yàn)執(zhí)行者洪健和王春霞次日全天待命，接受調(diào)查組問(wèn)訊。臧敬五立即與以上四人去東郊賓館吃晚飯并商量對(duì)策。他指使他們統(tǒng)一口徑，以掩蓋事實(shí)真相，其后臧敬五多次招集劉學(xué)彬、粱紹勤等人商量如何瞞天過(guò)海?？梢?jiàn)臧敬五不但完全知情而且參與合謀！

我不禁要問(wèn)藏總，1）您在許多場(chǎng)合（通常是酒后）提到您這篇得意之作時(shí)自豪地說(shuō)完成該文的實(shí)驗(yàn)?zāi)ㄙM(fèi)了1000多萬(wàn)元人民幣。現(xiàn)在看來(lái)，由于關(guān)鍵花錢的實(shí)驗(yàn)是自編的，您的1000萬(wàn)元都花到了何處？2）在您的全力推動(dòng)下，大干快上，將IL7受體抗體作為候選藥物推到了臨床試驗(yàn)階段。您有沒(méi)有自問(wèn)這個(gè)基于偽造實(shí)驗(yàn)數(shù)據(jù)的臨床試驗(yàn)會(huì)給GSK造成多大的經(jīng)濟(jì)損失、對(duì)患者的生命安全會(huì)造成多大的潛在威脅、對(duì)GSK的聲譽(yù)和股票會(huì)產(chǎn)生多大影響嗎？在這些時(shí)候您都想了些什么呢？3）您在很多場(chǎng)合的演講時(shí)都強(qiáng)調(diào)科學(xué)研究趨動(dòng)的新藥開(kāi)發(fā)是GSK中國(guó)研發(fā)中心的特色。當(dāng)您面對(duì)無(wú)數(shù)崇拜您的聽(tīng)眾時(shí)您有沒(méi)有手心冒汗？4）您在外把自己包裝成科學(xué)大師、自稱世界五大免疫學(xué)家之一，在內(nèi)卻沆瀣一氣，數(shù)據(jù)造假、灌水無(wú)所不用其極時(shí)，您想過(guò)什么是科學(xué)道德、為人師表、師道尊嚴(yán)嗎？5）我想再去調(diào)查您2013年3月發(fā)表在Nature Medicine 的論文或者2011年發(fā)表在 Immunity上的論文或者您剛剛修回到NatureImmunology的有關(guān)Sirt1調(diào)節(jié)RORgt的故事，己經(jīng)是浪費(fèi)時(shí)間了，這里面有幾斤干貨您心知肚明！您知道您描繪的所有這些海市蜃樓會(huì)在大霧散去太陽(yáng)升起之時(shí)消失嗎？

藏總，很多人都替您扼腕，因?yàn)槟斆鳌⒋竽?、敢想敢干！但凡事不能走極端！聰明太過(guò)就變成愚蠢，膽大就妄為！您膽子也忒大了一點(diǎn)，數(shù)年前您冒充世界五大免疫學(xué)家之一，被人當(dāng)作飯后笑料；還是數(shù)年前您無(wú)視法規(guī)擅自上臨床試驗(yàn)被美國(guó)FDA警告；兩年前您在NOGO項(xiàng)目上隱藏不良數(shù)據(jù)、粉飾太平、欺上瞞下，被GSK警告并勒令整改?。老天爺給了您如此多的機(jī)會(huì)痛改前非，重新做人，您為什么不要呢？唯一合理的解釋是利令智昏！為了權(quán)和利，您不擇手段??！您知道多少仁人志士，其中不乏您的舊友，為實(shí)現(xiàn)中國(guó)夢(mèng)，遠(yuǎn)道而來(lái)，投奔到您的麾下，結(jié)果，多少人飽受您的打擊報(bào)復(fù)而家破人亡、妻離子散嗎？用您常常引用的話結(jié)尾吧：whatdoes not kill you makes you stronger.

這次曝光的丑聞會(huì)因時(shí)間推移而逐漸淡出人們的記憶，但愿您因此而深刻反思，重新?lián)P起您高傲的頭，成為真正的強(qiáng)人！

論文檢索：

Xuebin Liu, Stewart Leung,Chunxia Wang, Zhu Tan, Ji Wang, Taylor B Guo, Lei Fang,YonggangZhao, Bing Wan, Xia Qin, Limin Lu, Runsheng Li, Heng Pan, MingjuanSong,Ailian Liu, Jian Hong, Hongtao Lu & Jingwu ZZhang.Crucial role of interleukin-7 in Thelper type 17 survival and expansion in autoimmunedisease. Nature Medicine, 10 January 2010; doi:10.1038/nm.2077

China drugs head fired over article row

Researcher stands by results despite demand for retraction.

Jingwu Zang says he is baffled by the whole affair. Until lastmonth, he was head of a neurodegenerative-disease research unit inShanghai, China, for London-based drug firm Glaxo­SmithKline (GSK).On 22May, as he tells it, his boss told him thatthere would be an investigation. The next day, Chinese lawyersshowed up at the company to interview him. On31May, he was told to hand in his computer andcompany credit card, and was escorted to his car. “Within a fewminutes, I was outside the facility I built,” he says.

On 9 June, hereceived a letter informing him of his officialtermination of employment.

The investigation has focused on a paper published in NatureMedicine that Zang co-authored on multiple sclerosis (MS), hisspeciality (X.Liuetal. Nature Med. 16, 191–197;2010). GSK is asking for the paper to be retracted; Zang standsby the results. The Chinese blogosphere is abuzz over the dispute,wondering what it signals for a centre seen as a bellwether forChina’s budding drugs industry.

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Zang set up the global research and development centre inShanghai in 2007. The centre was considered bold: of the manyinter­national pharmaceutical giants that had opened researchoperations in China in the previous five years, only GSK had givenits branch wide autonomy, with control over global operations foran entire development sector, that of neuro­degenerative diseases.“In Shanghai, we can make decisions that drive global studies,”says Zang.

Now with some 400 scientific staff, the centre has severalcandidate neuro­degenerative drugs in phaseI andII clinical trials, Zang says, and he was eager to get one throughphaseIII, to “demonstrate that we can do greatscience and move a clinical compound forward”.

Four years ago, Zang’s group started work on a protein calledthe interleukin-7 receptor (IL-7R). “It was a really excitingstory,” he says. IL-7R sits on the surface of certain immune cells,and a genetic variant of it had been linked to MS. Nobody knew whatthe underlying mechanism was, but Zang had a hypothesis — that theIL-7 pathway played a part in the pathogenic expansion ofT-helper17 (T_H17) cells, immune cellsthat, when present in excess, are thought to contribute to MS.

In 2010, the group published results in Nature Medicineconcluding that this was indeed the case. But last month, the papercame under scrutiny from within GSK after the company and NatureMedicine were notified of a problem with some of the data. AGSK investigation has since concluded that human blood samples usedto create a figure in the article — described in the caption asbeing taken from patients with MS — actually came from healthysubjects.

On 10June, GSK posted a statement saying:“Regretfully, our investigation has established that certain datain the paper were indeed misrepresented. We’ve shared ourconclusion that the paper should be retracted and are in theprocess of asking all of the authors to sign a statement to thateffect.”

“Regretfully, our investigation has established that certaindata in the paper were indeed misrepresented.”

Zang and Xuebin Liu, the paper’s first author, both say thatthis was an unintentional mistake that does not change the paper’soverall conclusion. Liu, whose group ran the experiment andcompiled the data, says that the team had hoped to use data fromcells of patients with MS and had drafted a manuscript with thatwording. But although preliminary data from patients did revealZang’s proposed link between the IL-7R pathway andT_H17cells, staining in those images was inadequate — sothe team turned to healthy subject data instead, Liu says. In ahurry to beat competition, they forgot to change the caption. Liusays that cells from either group can be used to show theeffect.

Liu also addressed another problem, noted later on apharmaceutical blog, after news of the investigation came out: twoimages, with captions describing different experimental conditions,are identical. Liu says that the mistaken duplication occurredduring editing and layout of the article, and has asked NatureMedicine to check. The journal’s chief editor Juan Carlos Lópezsays that he cannot comment yet.

The main thrust of the paper — that IL-7R is related to MS, andthat blocking its function can ameliorate MS-like disease in amouse model — largely agrees with results from other groups. Butscientists have failed to replicate the specific mechanism proposedby Zang’s team.

One of those studies, led by researchers at Stanford Universityin California and at Rinat, a subsidiary of the drugs giant Pfizerbased in South San Francisco, California, found that the effects ofblocking IL-7R largely agreed with the results from Zang’s group.But they were unable to reproduce the results of Zang and Liu’sexperiments that supported a connection between IL-7R andT_H17 cells as the mechanism. The discrepancy was “notlikely due to differences in the experimental protocols, because wediligently followed their methods”, the researchers wrote in their2011 report in Science Translational Medicine (L.-F. Leeetal. Sci. Transl. Med. 3,93ra68; 2011). Stanford’s Lawrence Steinman, a correspondingauthor on the California study, declined to comment.

But Liu says that the California experiment differed from theChina experiment in an important way: the GSK team used matureT_H17 cells whereas the California group usedundifferentiated ones. “It’s a different protocol, a differentstage,” he says.

Liu says that as first author he takes full responsibility forthe mistakes. On 9June, he announced hisresignation on a Chinese bioscience website. Both Liu and Zang saythat they stand by the paper’s results and will not sign a letterto Nature Medicine requesting that the paper be retracted.López says that a retraction is still possible, even if not all ofthe authors agree to it, “if confidence in the paper is lost”. Insuch cases, “the paper is still retracted, explaining who agreesand who doesn’t agree to the retraction”, he says.

Asked whether a retraction is warranted if the mistakes do notaffect the paper’s findings, David Daley, GSK’s director of globalexternal communications, acknowledges in an e-mail that in theperiod since the research was carried out, “an independent body ofevidence has accumulated that the receptor [for] interleukin-7(IL-7) is a valid target for a variety of autoimmune disorders”.But he adds that “because certain data in the publication weremisrepresented, we believe retracting the paper is the onlyappropriate action to take”.

Zang, who was involved in the experimental design and indrafting the manuscript, but not in the hands-on experiments ordata compilation, believes that he was fired not over datamisrepresentation but for allegedly “influencing theinvestigation”. The letter terminating his employment states thathe “wilfully and purposefully undermined and misled thisinvestigation and provided untruthful information” — charges hevehemently denies.

Daley declined to detail GSK’s reasons for terminating Zang’semployment, but provided a GSK statement: “We are confident in thethorough investigation we conducted and the actions we have takenas a result of our findings. We will not tolerate activity andbehaviour that falls short of the high standards expected from ouremployees.”

Zang says the whole episode is bizarre. “I still can’tunderstand it.”

Nature

498,

283–284

(20 June 2013)

doi:10.1038/498283a

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