◇◇新语丝(www.xys.org)(xys.dxiong.com)(xys.3322.org)(xys.xlogit.com)◇◇ 四川大学海归教授丘小庆在《自然》杂志造假蒙人 六位被骗者要求Nature Biotechnology撤消共同署名和共同作者权   主编先生:   我们作为2003年11月发表在贵刊上的标题为“An engineered multidomain bactericidal peptide as a model for targeted antibiotics against specific bacteria”一文的共同署名作者,现在正式向贵刊提出,要求你们公 开撤销我们在这篇论文的署名,因为我们不能容忍我们是一科学造假论文的共同 署名者。   我们之中有的是在通讯作者丘小庆实验室长时间参与PH-SA各类实验的工作 人员或参与药效测试者。我们之中有些事先被告知将被署名,但有些在该文发表 前并不知道自己是这篇论文的共同署名作者。更重要的是,因为我们都有英语障 碍,都不能准确流畅地阅读英文文章,而通讯作者丘小庆先生明知我们不懂英文, 却在文章发表前从未向我们说明过该文的内容,文章发表后,也从来没有向我们 这些共同署名作者解释过究竟他和另一通讯作者是怎样表述PH-SA的。   直至今年初,拥有PH-SA产权的四川新泰克控股有限公司和美国PRPHET公司 对PH-SA及其NATURE文章真实性进行调查时,PROPHET的科学顾问GEORGIA大学的 赵利军博士向我们翻译介绍了该文的内容,我们才知道原来我们共同署名了一篇 陈述了一个并不存在的发明的论文。   根据文章所述,作者发明的PH-SA具有极高的特异性,并反复地强调其所有 的实验数据都显示PH-SA只对有AgrD1受体的“Staphylococcus aureus(MSSA和 MRSA,金黄色葡萄球菌)”有抗菌活性,而对缺乏AgrD1受体的诸如"其它种类葡 萄球菌或其它类别细菌没有抗菌活性”。在文章前的黑体字摘要中,又特地指出 PH-SA“对表皮葡萄球菌或肺炎链球菌没有抗菌活性”,以此强调其所谓“特异 性”的根据。   作为此文的共同署名者,我们对这种科学造假感到惊诧,因为文章所声称的 PH-SA这种所谓的“特异性”是根本不存在的。由PH-SA产权的拥有者出资,通讯 作者丘小庆和我们都程度不同参与其中,在由四川抗生素工业研究所完成的对 “PH-SA主要药效学试验”,其结果恰恰与此文相反,PH-SA毫无此文所声称的那 种“特异性”。PH-SA的药效学试验清楚地证实了PH-SA对所测试的诸多无AgrD1 受体的细菌均呈现了强烈的抗菌活性。PH-SA不但杀死金黄色葡萄球菌(MSSA和 MRSA),也杀死表皮葡萄球菌(MSSE和MRSE),肺炎链球菌,甚至被测试的所有革 兰氏阴性菌。   以下是2003年3月15日加盖了四川抗生素工业研究所公章的“PH-SA主要药效 学试验”报告第七至第八页的摘录:   “(1)Ph-SA对所试耐甲氧西林/苯唑西林金葡菌(MRSA)菌株的抗菌作用很强, 其MIC50值为16mg/L,以MIC50值计算,抗菌活性强于万古霉素1.5倍,氨苄西林 200倍,青霉素1600倍,苯唑西林1600倍,头孢唑啉1240倍;对所试甲氧西林/苯 唑西林敏感菌(MSSA)菌株的抗菌作用也较强,其MIC值为0.5mg/L,抗菌活性强于 万古霉素48倍,头孢唑啉78倍,青霉素6400倍,氨苄西林200倍,苯唑西林50 倍。”      “(2)Ph-SA对所试甲氧西林敏感表皮葡萄球菌(MSSE)菌株也呈现了较强的抗 菌活性,其MIC50值为0.5mg/L,以MIC50值计算,抗菌活性强于万古霉素48倍, 头孢唑啉39倍,青霉素6400倍,氨苄西林100倍,苯唑西林50倍。”   “(3)Ph-SA对所试A群、B群链球菌和肺炎链球菌有一定抗菌作用,其MIC50 值均为8mg/L。以MIC50值计算,对该数种菌的抗菌活性强于万古霉素3倍,头孢 唑啉20-620倍,青霉素12-200倍,氨苄西林3-12倍,苯唑西林6-400倍。”      “(4) Ph-SA对所试其它革兰阳性菌如赛氏葡萄球菌、中间型葡萄球菌、肠 球菌和链球菌的抗菌活性较弱,MIC50值均大于64mg/L。”   “(5) Ph-SA对所试革兰阴性菌中大肠埃希氏菌、肺炎克雷伯氏菌、铜绿假 单胞菌、阴沟肠杆菌、枸橼酸杆菌、变形杆菌、嗜水气单胞菌均有一定抗菌活性, MIC50值分别为32、1、8、8、0.5、0.5和32mg/L,其活性均强于其它五种抗生 素。”   这是无可辩驳的事实,四川抗生素工业研究所的药效学试验证明了PH-SA毫 无特异性可言,在贵刊发表的这篇英文文章所表述的所谓“特异性”纯属通讯作 者的杜撰。   在川抗所完成的这项实验所用的蛋白全部产自于丘小庆在川大的实验室或由 丘小庆主持,川大和NTC的联合实验室。这项实验属于PH-SA在中国正式的临床前 研究的药效学部分。通讯作者丘小庆和我们都程度地不同参与了这项工作,都知 道2003年3月15日四川抗生素工业研究所出具的“PH-SA主要药效学试验”报告的 存在。   我们之中有些人也一直知道丘的PH-SA从未达到过90%以上的纯度,也一直怀 疑这篇英文。事实上,就在贵刊发表此文的前三个星期,即2003年10月下旬,与 新泰克公司合作的西藏药业公司的药物研究所曾经向丘小庆提出过其蛋白表达制 备的方法问题,并明确地质疑其PH-SA强烈的抗菌活性可能是其表达制备过程中 加入高浓度链霉素后的残留所致。但是丘小庆却竭力掩盖事实真相,继续操纵愚 弄包括我们这些共同署名作者在内的所有相关人员。   我们也被告知了对PH-SA核实实验的结果,根本不存在在贵刊发表的这篇文 章所声称的这个功能蛋白。核实实验同时也解释了为什么在川抗的“主要药效学 试验”中,PH-SA呈现了毫无特异性却对被测试的所有革兰氏阴性菌都杀的现象, 这全是在表达制备过程中加入的高浓度链霉素后的残留所致。当链霉素残留去除 后,PH-SA毫无任何抗菌活性。我们也被告知,这一科学造假事件背后,受害者 四川新泰克控股有限公司,和美国PRPHET公司多次质询四川大学“在NATURE BIOTECHNOLOGY上所表述的一模一样的功能蛋白在哪里?”但是,川大或丘却不 能提交这个蛋白, 因为它从来就没有存在过。   铁的证据已经无可辩驳地证实了这篇英文文章所声称的所谓“发明”纯属伪 造。川抗的“主要药效学试验”报告及其出具的时间证明了此文声称的数据和 “发明”是科学造假,核实实验解释了所谓的“PH-SA”为何有如此强烈却毫无 特异性的抗菌作用。因为英语障碍,我们在不了解内容的情况下变成了共同作者。 现在真相大白,为了科学界的尊严,同时也是为了我们自己的声誉,责任和尊严, 因为我们不能成为科学造假者的一个组成部分,所以,在此正式向你提出在贵刊 公开地撤消在An engineered multidomain bactericidal peptide as a model for targeted antibiotics against specific bacteria”一文的署名。   此致   敬礼   左俊勇 杨莉 周雨祺 王海云 张淑华 欧真容   附件:   1) “PH-SA主要药效学试验”, 四川抗生素工业研究所, 2003年3月15日   2) “PH-SA主要药效学试验”, 英文翻译本   3) “PH-SA药学研究综述”, 西藏华西药业集团公司 2005年2月1日   4) “PH-SA药学研究综述”, 英文翻译本 December 18, 2005 Editor in Chief Nature Biotechnology 345 Park Avenue South New York NY 10010-1707 Dear Mr. Editor in Chief: As co-authors of the article entitled “An engineered multidomain bactericidal peptide as a model for targeted antibiotics against specific bacteria”, published in your journal on November 15, 2003, we are writing this letter to request that our names and co-authorship be officially withdrawn from this article. We can not tolerate to be manipulated by the corresponding author, Mr. Xiao-Qing Qiu (“corresponding author” or “Qiu”) and remain a part of scientific fabrication. We co-authors used to work at the corresponding author’s lab and over the years either participated in PH-SA project or were involved in pharmaceutical efficacy studies on PH-SA. Some of us were informed by Mr. Qiu that our names would be printed on the article as co-authors, while some of us were not made aware we were co-authors prior to this article being published. More importantly, all of us have a limited ability with English and can not accurately read English very well. Mr. Qiu knows our language barrier and never explained to us the content of paper. He also never explained to us how the corresponding authors presented PH-SA on this article, even after it was published. Earlier this year, the legal owners of PH-SA, NTC Holding Ltd. of China (“NTC”), and Prophet Biopharmaceuticals, Inc, of USA (“Prophet”) started an investigation in to the existence of PH-SA. The scientific advisor for Prophet, Dr Lijun Zhao of University of Georgia, translated and explained the content of this article to us. Then is when we realized that we were co-authors to an article that presented PH-SA in a way that does not exist. According to this article, the “authors” claimed PH-SA was engineered very highly specified and repeatedly stressed that all data indicated PH-SA would only kill the bacterial with pheromone receptor AgrD1 S. aureus (MSSA and MRSA), but would not kill bacterial lacking the pheromone receptor such as “other staphylococcal species or other bacterial”. In their bolded summary, the authors pointed out specifically that PH-SA reacted “not against Staphylococcus epidermidis or Streptococcus pneumoniae”; in order to emphasis their “specificity”. We are shocked by this scientific fabrication because the “specificity” that the article claimed definitely does not exist. The results of an official pharmaceutical study on PH-SA (“pharmaceutical Study” or “study report”) are in fact contrary to the article. In this study, PH-SA showed bactericidal activity not only against MSSA and MRSA, but also against Staphylococcus epidermidis and Streptococcus pneumoniae, and other bacterial including all gram negative strains tested in this study. This study was financed by the owner of Ph-SA, and conducted by National Sichuan Antibiotic Industrial Institute, Pharmacy Group of China. Mr. Qiu and the other six co-authors participated in this study. The following 5 conclusions are quoted from the official study report “In Vitro and In Vivo of PH-SA Effect Comparison” page 7 to 8 (English translation page 8 to 9), sealed and issued by National Sichuan Antibiotic Industrial Institute, Pharmacy Group of China on March 15, 2003: “(1) Ph-SA presented very strong bactericidal activity against Staphylococcus aureus MRSA. MIC50 was 16mg/L. Based upon MIC50 values, bactericidal activity of Ph-SA was 1.5 times higher than that of vancomycin, 200 times higher than that of ampicillin, 1600 times higher than that of penicillin, 1600 times higher than oxacillin, and 1240 times higher than that of cephazolin. It also presented very strong bactericidal activity against MSSA. MIC value was 0.5mg/L. Its activity was 48 times higher than that of vancomycin, 78 times higher than that of cephazolin, 6400 times higher than that of penicillin, 200 times higher than that of ampicillin and 50 times higher than that of oxacillin.” “(2) Ph-SA presented very strong bactericidal activity against Staphylococcus epidermidis MSSE. MIC50 was 0.5 mg/L. Based upon MIC50 values, bactericidal activity of Ph-SA was 48 times higher than that of vancomycin, 100 times higher than that of ampicillin, 6400 times higher than that of penicillin, 50 times higher than oxacillin and 39 times higher than that of cephazolin.” “(3) Ph-SA presented certain bactericidal activities against pyogenic Streptococcus, Streptococcus aglactiae and Streptococcus pneumoniae. MIC50 values were 8 mg/L. Based upon MIC50 values, bactericidal activity of Ph-SA was three times higher than that of vancomycin, 3-12 times higher than that of ampicillin, 12-200 times higher than that of penicillin, 6-400 times higher than oxacillin and 20-620 times higher than that of cephazolin.” “(4) Ph-SA presented certain weak bactericidal activities against tested Gram-positive bacteria, such as other Staphylococci, Enterococci and Streptococci. All MIC50 values were larger than 64 mg/L.” “(5) Ph-SA presented certain bactericidal activities against other Gram-negative bacteria, such as E.coli, Klebsiella pneumonia, Pseudomonas aeruginosa strains, Enterobacter cloacae, Citrobacter, Proteus, Acinetobacter and Aeromonas hydrophila. MIC50 values were 32、 1、8、8、0.5、0.5 and 32mg/L respectively. These activities were more effective than all control antibiotics.” The above conclusions presented in “In Vitro and In Vivo of PH-SA Effect Comparison” indisputably demonstrated that there is no such existing highly specific functional pheromonicin. This strongly indicates that the article printed in Nature Biotechnology was a deliberate scientific forgery and completely fabricated by the corresponding authors. All of the proteins used in this pharmaceutical study were produced by the corresponding author, Mr. Qiu, either from his Sichuan University lab, or in a lab which was jointly funded by NTC and the University. Mr. Qiu and all of us participated in this study and clearly knew about the existence of this final official report issued by National Sichuan Antibiotic Industrial Institute, Pharmacy Group of China on March 15, 2003. Some of us began to realize Mr. Qiu’s PH-SA never purified to 90% and suspected the accuracy of this Nature Biotechnology article. In fact, in October, 2003, just three weeks before the Nature Biotechnology article published, pharmaceuticals research institute of Tibet West China Pharmaceuticals Group Inc., a corroborator with NTC, questioned Mr. Qiu concerning his protein expression process and frankly expressed their suspicion that the bactericidal activity of PH-SA is caused by highly concentrated streptomycin sulfate remaining, not a functional protein. However Mr. Qiu just evaded this critical issue and continued to manipulate data to fool all related parties. We are told by NTC and Prophet that the results of the verification experiment on PH-SA by Tibet West China Pharmaceuticals Group Inc. did not identify any such identical and functional protein that this article claims existed. This verification experiment also explained why PH-SA showed completely no specificity but so strong bactericidal activity against almost all of bacterial including gram negative strains. It is streptomycin, not the author’s so called “pheromonicin” that kills MSSA and MRSA. After the remaining streptomycin sulfate was removed from the pheromonicin samples they did not demonstrate any non-specific antibacterial activities. We are also told by NTC and Prophet that they inquired several times to Sichuan University, the seller of PH-SA requesting the identical and functional protein that was presented in the Nature Biotechnology article. They never provided such protein because it has never existed. All of the hard evidence indisputably proved this article published in your journal (in English) is a scientific fraud. The Pharmaceutical Study Report demonstrates the data and “invention” that was presented in this article is scientific fabrication. Because of our English barrier, we were misled by the corresponding authors to become co-authors of this article. For our own professional reputation, responsibility and moral principle, as well as the sake of the dignity of the scientific community, we request officially and publicly to withdraw our names and co-authorships from this article because we can not remain connected to this scientific fabrication. Very Truly Yours, Jun-Yong Zuo, Yang Li, Yu-Qi Zhou, Hai-Yun Wang, Su-Hua Zhang, Zheng-Rong Ou Enclosure: 1) Pharmaceuticals Study Report: “In Vitro and In Vivo of PH-SA Effect Comparison”, Chinese Version, sealed and issued by National Sichuan Antibiotic Industrial Institute, Pharmacy Group of China on March 15, 2003. 2) Pharmaceuticals Study Report: “In Vitro and In Vivo of PH-SA Effect Comparison”, English Translation. 3) Verification Experiment Report: “The Summary of PH-SA Tests”, sealed and issued by Tibet West China Pharmaceuticals Group, Incorporated on February 1, 2005. 4) Verification Experiment Report: “The Summary of PH-SA Tests”, English Translation. (XYS20051231) ◇◇新语丝(www.xys.org)(xys.dxiong.com)(xys.3322.org)(xys.xlogit.com)◇◇