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科学论文鬼故事
2009.12.18
天下之大，真是无奇不有。
今天出版的Science上有一个关于科学论文的鬼故事。有兴趣的网友请看以下链接。
Science杂志2009年12月18日“SCIENTIFIC INTEGRITY: A Dark Tale Behind Two Retractions”文章链接：http://www.sciencemag.org/cgi/content/full/326/5960/1610
这个鬼故事的主角是大名鼎鼎的Peter Schultz和他的前博士后Zhang Zhiwen博士。
前几年哥伦比亚大学化学系出过一件研究生造假的严重事件。上个礼拜一位知情人告诉我了其中的一些内情。
那位造假研究生的年轻导师因为太相信她（奥林匹克化学竞赛铜牌女得主）的创新成果，居然很长一段时间认为不能重复出造假数据的几个低年级研究生水平太差，把他们给开除了。直到另一位也深受导师信任的高年级研究生发现自己无论如何也不能重复那些结果，导师才决定系统地检查究竟是什么地方出了差错。
在后来的重复试验中，他们发现一直不能重复的实验结果居然奇迹般地又能够被重复了。于是他们设了一个圈套，故意把药品用量在记录本中多写十倍，第二天反应结束后居然真的出现了十倍的产率，远超过了按照实际用量可能的100%的理论产率。于是他们才明白那一段时间的重复试验中一定有人在反应过程中往反应器中按照假设的反应产物量添加纯的产物。结论只能是那个反应的确是不能重复的，而且有人在捣鬼。那个暗中添加产物的鬼，就是那个造假的女研究生。因为查出了原因，那个年轻教授最后被判定没有直接责任，但他的学术声誉的确大受影响。他的那几个被开除的学生，也比窦娥还冤。
和那位年轻教授不同的是，Peter Schultz早已是功成名就。现在这件事情也许只会对他将来更上一层楼有重大影响。
最大的问题是，到目前为止，那个鬼还没有被抓到。
有意思吧！
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来源：http://www.sciencemag.org/cgi/content/full/326/5960/1610
Science 18 December 2009:
Vol. 326. no. 5960, pp. 1610 - 1611
DOI: 10.1126/science.326.5960.1610
NEWS OF THE WEEK
SCIENTIFIC INTEGRITY:
A Dark Tale Behind Two Retractions
Robert F. Service*
The notices published in Science last month and online in the Journal of the American Chemical Society (JACS) in September were brief: Two papers from a prominent chemistry lab were being retracted because the results couldn't be replicated. Part of the story behind the retractions is anything but straightforward, however. It involves an extortion attempt and a threat of suicide.
The papers were published in 2004 from the laboratory of Peter Schultz, a chemist at The Scripps Research Institute in San Diego, California. They extended pioneering work in Schultz's lab on a method for incorporating non-native amino acids into proteins (Science, 20 April 2001, p. 498). Conventional proteins are made up almost exclusively of 20 amino acids that are coded for by DNA, though hundreds of other amino acids occur naturally. Schultz and his colleagues offered biologists a way to incorporate some of these nonstandard amino acids, which could then serve as novel chemical handles to manipulate proteins of interest. Today, dozens of these chemical handles are used by everyone from drug-makers to cell biologists looking for new ways to understand how proteins function.
In 2004, Zhiwen Zhang, then a postdoc in Schultz's lab, and several other co-authors reported in Science that they had extended the technique to introduce an unnatural amino acid that came preloaded with a specific sugar group (Science, 16 January 2004, p. 371). Such sugar groups are common appendages on glycoproteins. But because the sugars are difficult to express uniformly and to purify, understanding their role has long been viewed as a major challenge. The Science paper offered researchers the possibility of systematically studying the effect of different ways proteins are modified. On 11 November 2004, Zhang, Schultz, and their colleagues published a second paper in JACS reporting the incorporation into a protein of a sugar-loaded amino acid that's a core unit in glycoproteins central to inflammation and cellular recognition.
At about the time of the Science paper, Eric Tippmann joined the Schultz lab as a postdoctoral assistant. Like Zhang, Tippmann worked on efforts to extend the technique of incorporating unnatural amino acids into proteins. A few months after Tippmann's arrival, Zhang left the Schultz lab to take a tenure-track position as an assistant professor of pharmacology at the University of Texas (UT), Austin. Tippmann says he became interested in Zhang's work because fellow students and postdocs told him they were having trouble replicating it. Tippmann says he reviewed Zhang's work closely in the fall of 2006. In September 2006, Tippmann spoke at a Schultz group meeting outlining reasons why he thought Zhang's work was likely incorrect.
Schultz says the concerns raised were serious enough that he asked a group of lab members to try to replicate the work in Zhang's Science paper in addition to several other important discoveries Zhang had made. That task, however, was complicated by the fact that Zhang's lab notebooks, describing his experiments in detail, were missing. Schultz says that in the early fall of 2006, the notebooks were in Schultz's office. But at some point after that they were taken without his knowledge and have never resurfaced.
After considerable effort, Schultz says his students were able to replicate most of the work. The biggest exception was the work that served as the basis for the 2004 Science and JACS papers. "It was clear the glycosylated amino acid work could not be reproduced as reported. So we tried to figure out what was going on," Schultz says.
In the midst of this process, events took an ominous turn. On 1 March 2007, Zhang received an e-mail that listed the author as "michael pemulis," who claimed to have discovered "fraud" in multiple papers. If Zhang did not send $4000 via overnight mail to a post office box in San Diego, the e-mail sender said he or she would reveal this "fraud" to faculty at Scripps and UT Austin. "They will investigate you. ... pete will retract all your post-doctoral work. you lose job. ... Texas will fire you before you tenure," the e-mail states.
"I was scared to death," Zhang recalls. He immediately contacted Schultz, who in turn contacted Richard Lerner, president of Scripps. At Lerner's urging, Schultz and Zhang then contacted the San Diego Police Department, which forwarded their case to its electronic crimes unit. About a month later, in April 2007, Zhang says the officer in charge of the case told him that they had a suspect and asked whether he wanted to press charges. Zhang says he decided not to do so in hopes the situation would blow over.
It didn't blow over. In November 2007, an anonymous letter was sent to officials at several institutions, including Scripps; UT Austin; the University of California, Berkeley; and Science's editorial department. The letter stated that it was from "a member of PGS [Peter G. Schultz] lab" and called the 2004 Science paper a "fake." "I feel like leaving science or committing suicide," the letter stated. Zhang says that when he saw the letter, "my jaw dropped again."
The disturbing events haven't stopped. Zhang says over the past 2 years, he has received several anonymous phone calls at his UT Austin office phone number in which the caller hasn't said anything and then hangs up. Zhang says he's tried calling the number that pops up on his caller ID, but a recording on the other end says it is a long distance calling card center in Mississippi. Zhang says he and his family have become unnerved: "We don't feel safe anymore." The stress has gotten so high, that his wife and children moved away from Texas some time ago and have since been in virtual hiding. "It's horrible," Zhang says. "I'm just trying to be a good scientist. This is not science."
The events, Schultz says, affected him deeply as well. "It put me in a situation where I felt there was an extra burden on me to find out what was going on, given the threats," he says. Today, after years of effort, Schultz says he feels he and his students are starting to understand what may have gone wrong with the original experiments. Although still preliminary, it appears that the problem might be with the enzyme that they thought was binding to the unnatural amino acid and incorporating it in the protein. A test with a different glycosylated amino acid shows that it actually binds the unnatural amino acid not in the normal "active site" but at another site. Here it then prompts a conventional natural amino acid to be incorporated in the active site, giving a false positive reading. In the end, Schultz says, Tippmann was right to have doubts. "There was something wrong with the work."
That meant the Science and JACS papers needed to be retracted. Zhang says Schultz contacted him in July and suggested that the papers be pulled. Zhang was preparing for his tenure review at UT Austin and says he was concerned that retracting the papers would prove damaging to his chances of receiving tenure. Nevertheless, after Schultz and Zhang talked it over, they agreed to retract both papers. After receiving signed agreement from each of the authors, a process that took several weeks, Schultz sent the retractions to Science and JACS on 11 August.
JACS quickly accepted the retraction. But editors at Science informed Schultz that the journal's editorial practice requires that they get signatures directly from all authors wishing to retract a paper. During that process, Zhang informed Science's executive editor, Monica Bradford, of the extortion e-mail and the missing lab notebooks. In response, Science's editor-in-chief, Bruce Alberts, called Schultz to suggest that the retraction letter in Science should state that the lab notebooks were missing through no fault of the authors; that wording helped explain why they had trouble replicating the experiments. In the end, the retraction was published on 27 November.
The summer brought other developments. On 7 August, Tippmann, now a lecturer at the University of Cardiff in the U.K., co-authored a paper that laid out several reasons why Zhang's original glycosylated amino acid experiments could not have worked. And in October, Zhang was told he would be denied tenure by UT Austin. For his part, Tippmann says he's sorry that Zhang has had to undergo this ordeal, but that his involvement has been entirely limited to the science, and he had nothing to do with the missing notebooks, the March 2007 e-mail sent to Zhang, or the November 2007 letter. Schultz says he and his Scripps colleagues will continue to search for answers. Lerner concludes: "There was somebody who did this, really turned lives upside down, and made doing science a lot harder than it had to be."
* With reporting by Michael Torrice.
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