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Science paper pulled

Researchers are retracting a highly-cited linkurl:2004 Science paper;http://www.sciencemag.org/cgi/content/abstract/303/5656/371 describing a new way of adding sugars to proteins -- a longstanding challenge in molecular biology -- citing their inability to repeat the results and the absence of the original lab notebooks with the experiment details, they linkurl:announced;http://www.sciencemag.org/cgi/content/full/326/5957/1187-a in Science last Thursday (November 26). Image: Wikimedia commons"

By | November 30, 2009

Researchers are retracting a highly-cited linkurl:2004 Science paper;http://www.sciencemag.org/cgi/content/abstract/303/5656/371 describing a new way of adding sugars to proteins -- a longstanding challenge in molecular biology -- citing their inability to repeat the results and the absence of the original lab notebooks with the experiment details, they linkurl:announced;http://www.sciencemag.org/cgi/content/full/326/5957/1187-a in Science last Thursday (November 26).
Image: Wikimedia commons
"It is unfortunate that they cannot repeat it," said biochemist linkurl:Lai-Xi Wang;http://medschool.umaryland.edu/FACULTYRESEARCHPROFILE/viewprofile.aspx?id=7742 of the University of Maryland School of Medicine, who did not participate in the retracted research. "This method opened a new avenue for the preparation of glycoproteins [with] huge potential in this field." Glycosylation, the addition of sugars to proteins, is a common posttranslational modification that is found on some 70% of human proteins. It can affect a variety of protein functions, including folding and biomolecular recognition, but the exact relationship between the structural and functional changes remains elusive. One of the reasons studying glycosylation is so difficult is the seemingly random manner in which glycoproteins are created. The unpredictable process results in a mixture of different glycoproteins with the same peptide backbone, and reliably producing pure samples of a single form -- important for studying the structure-function relationship -- has proven difficult. "There's no efficient way to make a defined glycoprotein with a sugar attached," Wang said. The 2004 Science study, published by linkurl:Peter Schultz;http://schultz.scripps.edu/ of The Scripps Research Institute in La Jolla, California and his colleagues, was heralded as a breakthrough because it proposed a method to artificially tack on sugars to a specific location of a protein in a predictable manner. Their strategy: Create a transfer RNA (tRNA) molecule that selectively binds a pre-modified amino acid -- one with the sugar already on it -- that would be incorporated during protein synthesis in E. coli, resulting in a glycosylated protein prior to any posttranslational additions. Schultz's lab had previously used this technique to incorporate other modified amino acids into proteins, and this study, published in Science, was the "proof of concept" that the same strategy could be applied to glycosylation, Wang said. "It was a big deal." But according to the retraction announcement released by Schultz and his colleagues last week, they have not been able to reproduce these results. "There are clearly complexities associated with suppression and cellular bioavailablity of these and other glycosylated amino acids that we did/do not understand," Schultz wrote in an email to The Scientist, "and, regrettably, we no longer have the notebooks to help resolve these issues (through no fault of any coauthors)." Another one of Schultz's papers, linkurl:published in the Journal of the American Chemical Society (JACS);http://pubs.acs.org/doi/abs/10.1021/ja044711z less than nine months after the 2004 Science report, was also linkurl:recently retracted.;http://pubs.acs.org/doi/abs/10.1021/ja906705a The JACS paper showed the applicability of the technique for the incorporation of a different glycosylated amino acid. ("The two withdrawal letters were submitted at the same time, but the processes of the two journals differ so the time to publication varied," Schultz said.) The Science paper has been cited 92 times, and the JACS paper has been cited 37 times, according to ISI. Schultz said that he and his team "will continue to work to understand the difficulties associated with the incorporation of glycosylated amino acids." In the meantime, they will continue to send reagents that incorporate a large number of other modified amino acids to hundreds of labs worldwide, Schultz said. "I'm still optimistic about the concept," said Wang. "But unfortunately so far it has not worked on the glycosylated amino acids."
**__Related stories:__***linkurl:Sweet Attachments;http://www.the-scientist.com/article/display/54587/
[May 2008]*linkurl:Off-the-shelf glycoprotein detection methods;http://www.the-scientist.com/article/display/54593/
[May 2008]*linkurl:Sugars And Splice: Glycobiology: The Next Frontier;http://www.the-scientist.com/article/display/18654/
[19th July 1999]
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Comments

Avatar of: anonymous poster

anonymous poster

Posts: 3

November 30, 2009

It will be interesting for someone to track down some of the citations of this article to see if negative findings were reported, and that prompted an eventual retraction. The system of public evaluation seems to have worked, but it seems to have taken longer than expected.\n\ncdb
Avatar of: anonymous poster

anonymous poster

Posts: 5

November 30, 2009

How, possibly, could the lab notebooks be missing? Was NIxon's secretary involved? \n\nIn this litigious society, I would think that all labs would keep at least one copy of everyone's notes in a safe place. This raises some serious concerns about overall credibility.
Avatar of: anonymous poster

anonymous poster

Posts: 85

November 30, 2009

I agree with the commenter whose eyebrows figuratively went up at the notion that the notebooks were missing but that it wasn't anybody's fault. When I was trained by my pre- and post-doctoral mentors (decades ago), it was DRILLED INTO ME that lab notebooks were vital, that they were permanent records of how experiments were conducted and interpreted, that they were the property of the institution in which the lab was located, and that they stayed with the lab and were never, never discarded. My mentors had notebooks going back decades! When I left the lab, I photocopied whatever pages I needed to take with me in order to write manuscripts off-site, but the originals always stayed in the lab in which they were created. \n\nI acknowledge that some biology labs may not provide proper training nowadays as pertains to the maintenance of lab notebooks (heck, some labs don't even provide proper training as pertains to experimental controls! But that's another story). However, I find it quite unbelievable that a predominantly "chemistry" lab would not keep such notebooks properly in all respects. To chemists, lab notebooks are culturally sacrosanct.\n\nPlus, without notebooks, you can't expect to get patents for your work. \n\nI certainly hope Dr. Schultze's institution doesn't sweep this "anomaly" under the proverbial rug.\n\n
Avatar of: anonymous poster

anonymous poster

Posts: 5

November 30, 2009

This just does not make sense. There were multiple authors and it even looks like another lab working in this area in the JACS retraction. Are ALL the notebooks missing? Are you trying to tell me that a group of 50 or so smart people down there at Scripps couldn't pull off one critical experiment in the field they invented? If the experiment was so damn important, you would think that maybe the author could remember something about it, despite not having his notebooks. It was a Science paper afterall! How the editors of these journals let them publish these types of retractions is a good question. Shame on the editors, they too do a disservice to the integrity of science.
Avatar of: anonymous poster

anonymous poster

Posts: 77

December 1, 2009

While not a chemist or biologist, I cannot comment on the traditions in those fields. However, as a behavioral scientist, I will say that in our highly automated labs, the protocols, dates, times etc are routinely recorded with the raw data, as are the data analysis programs and results, so that notebooks are given much less, if any, priority. In most cases, the data-acquisition, control programs, the data, analyses etc are not left to the vagaries of magnetic or optical media, but are still printed out on paper to be stored as record of the experiment.\n\nIn the present case, it is indeed suspect that all records would be missing - as is the silence on others' attempts to replicate such an important finding. Further, I don't think it is peculiar to my area of specialty that extraordinary "breakthroughs" require extraordinary proof or evidence and that any call for raw data and procedures requires, without any needed justification by the requester, for immediate and complete disclosure of same or forfeiture of one's credibility. Maybe that is what has been lost here.
Avatar of: Sarvesh Kumar

Sarvesh Kumar

Posts: 5

December 1, 2009

This was really funny to read that lab diary of such a revolutionary? research r missing.It reminds me of almost the similar story about thirty five years back about High Lysine content in one of the mutated strain of wheat by one of the most reputed scientist of Asia which could never be repeated in further trails.I wish to quote this with the idea that Scientists n Editors should excercise maximum restrain n be doubly sure in confirming such high profile findings before publishing them in widely acclaimed reputed scientific periodicals.This should be taken as a lesson for future.
Avatar of: anonymous poster

anonymous poster

Posts: 1

December 1, 2009

This retraction was published because of the hard work and perseverance of Dr. Eric M. Tippmann. \n\nIn fact, JACS and Schultz both thwarted Dr. Tippmann?s research in a vain attempt to preserve Schultz's integrity. The curious relationship between Schultz and the JACS editors impedes progress and calls into question the objectivity and purpose of JACS.\n\nSolely blaming missing notebooks for not being able reproduce results is an insult to science. To expect me to accept such a flimsy excuse infuriates and disappoints. Mostly because I am a level 2 Wizard and the contents of those notebooks may have been relevant to my interests. But enough about me.\n\nCall it what it is: intentional oversight and fraud. \n
Avatar of: PAUL STEIN

PAUL STEIN

Posts: 61

December 1, 2009

If the glycosylation of proteins was such a big feat that might revolutionize the field, as pointed out in the article, why has it taken five years to figure out that what Schultz et al. originally said they performed could not be done by anyone else? Besides Tippmann and colleagues, hasn't anyone else tried to venture into the field in all that time?\n\nPharma? Biotechs? Anyone?
Avatar of: anonymous poster

anonymous poster

Posts: 2

December 1, 2009

This is the strangest retraction yet in Science.The loss of the original notebooks ...now that is quite funny!! What is stranger is that they have methods for several other papers. (Do these other methods have anything to do with the Science paper?).\n\nIt has been said that you are a nobody in science if you've never had a retraction.....means your empire isn't big enough.\n\nPlease go easy on the Dr. Schulz as he seems to be publishing a paper a week.
Avatar of: anonymous poster

anonymous poster

Posts: 1

December 1, 2009

GlycoFi solved this problem independently; were acquired by Merck for $400M.
Avatar of: anonymous poster

anonymous poster

Posts: 2

December 2, 2009

How can the lab books of everyone involved be missing? And the data associated with the work, surely that is still on a computer or server somewhere. Records of oligos ordered, mass spec data, dates of these experiments. If Scripps has any integrity, there will be an internal investigation.\n\nThe truth is that this retraction happened because of this paper by Eric Tippmann's group:\nhttp://www.ncbi.nlm.nih.gov/pubmed/19666472?\nwhich basically shows that the work originally claimed is biologically impossible. \n\nTo my mind the first author of the Science and JACS papers should lose his current job as a professor, which he got based on these now retracted papers.\n\nAnd Peter Schultz should be ashamed for for such a blatantly cynical retraction. He should have just put his hands up and said his lab is too big to keep track of everyone, and given the pressure on people to produce results at any costs, stuff like this sometimes happens. \n\nThe sad fact is, had it not been for Tippmann's persistence and paper in JBC, this fraud would have been left to stand. \n
Avatar of: anonymous poster

anonymous poster

Posts: 2

December 2, 2009

This is how to retract a paper:\nhttp://www.nature.com/nature/journal/v417/n6887/full/417468a.html\n\nAlan Fersht had some class, and gives an honest account of why they are retracting. Not some rubbish about lost notebooks!
Avatar of: anonymous poster

anonymous poster

Posts: 77

December 2, 2009

Good post. More accurately, 3 out of 4 showed subject status - which I take to be the minimum proportion of scientists getting a bad rap from an overly ambitious minority.
Avatar of: anonymous poster

anonymous poster

Posts: 2

December 2, 2009

I don't know the real cause for the retraction. But I did read Dr. Tippmann's JBC paper. It's an average work to the best, not enough evidence to discredit the Science article. But since he was the member of the same lab and at about the same time, he (maybe other lab members as well)knew something we don't know. I applaud JBC editor's courage to publish the paper though I don't think it's of JBC quality.
Avatar of: anonymous poster

anonymous poster

Posts: 125

December 2, 2009

Just think of all the resources, time, and labor that other labs must have squandered unknowingly by basing their own research on the retracted paper, due to its unproven result. That's the real harm done whenever dubious papers get published in the high-profile journals that other researchers take for granted as being the most reliable source of legitimate science for their own research. It's pretty unfortunate and sad, really.
Avatar of: tarun vishta

tarun vishta

Posts: 1

December 5, 2009

it might be from my point of view that there are certain forces that are acting on that preamino acid which are not letting this product to be stable before it could be glycosylated & one of the factor might be stearic effect & sreoisomerism of that compound .
Avatar of: anonymous poster

anonymous poster

Posts: 5

December 5, 2009

I second the comment below on the low quality of the Tippmann JBC paper. It lacks any solid grasp of the English language, and that's the coherent portions! Its written as if someone took a bunch of issues of disparate journals, shredded them, and then forced them out through a paintball gun onto the pages of JBC. I mean, actually citing the literature OTHERS have produced in journals with impact factors nearer zero than ten, and expecting referees and readers to go scouring through these obscure specialist journals to make meaning of it all, rather than simply redoing all the necessary experiments then and there? Well the approach to science used by Tippmann and coworkers is unsustainable for sure, inconsiderate at best, and an affront to referees that have their own confounding papers to reformat and resubmit. Well I guess, when the going gets weird, the weird turn pro.
Avatar of: anonymous poster

anonymous poster

Posts: 1

December 7, 2009

What does the quality of the Tippman paper really have to do with this discussion? Choose a profession, science or politics. The problem at hand is not the quality of Dr. Tippman's article. The problem is that Dr. Schultz cannot find his notebooks, the basic application of the fundamentals of Research 101?\n\nSome would have you believe that in research, good English is more important than ethical research practices.
Avatar of: anonymous poster

anonymous poster

Posts: 2

December 8, 2009

the quality of the Tippermann should not have anything to do with the retraction. But the timing is. Also wonder how it got published in JBC, considering its quality. \nSomebody earlier said Schultz, maybe Wong as well, tried to fence off the retraction. It may have some truth to it. JACS is the lead publication of ACS while JBC is published by ASBMB. ASBMB is playing the role of a judge here.
Avatar of: anonymous poster

anonymous poster

Posts: 2

December 18, 2009

\nArticles in Nature and Science discussing this retraction:\n\nNature\nScience\n\nI wouldn't be too quick to judge any party in this situation. It seems to be much messier than anyone anticipated.
Avatar of: anonymous poster

anonymous poster

Posts: 2

December 18, 2009

Sorry, the links were fine when I pre-viewed them. Here are the web addresses:\n\nhttp://www.nature.com/news/2009/091218/full/news.2009.1152.html\n\nhttp://www.sciencemag.org/cgi/content/full/326/5960/1610
Avatar of: eric tippmann

eric tippmann

Posts: 5

January 11, 2010

When I arrived at Scripps, I knew nothing of molecular biology, having come directly from completing a PhD in Physical Organic Chemistry. Very few other labs could have afforded me the time, or leeway, necessary to cut my teeth in a completely new research area. In this regard, I am very pro-megagroup. In regards to the Science and Nature articles that followed up on the Schultz retractions, they gloss over several key facts that I insisted should be included. The first fact was that Merck?s nearly $500 million acquisition of GlycoFi in 2006 means that there are still viable alternatives to the production of glycosylated proteins; and therefore reason to remain optimistic about the field in general (i.e. fund grants). The second fact was that at least two other Scripps? post-docs, as well as an undetermined number of biomedical companies, began working full-time on reproducing the now retracted papers already in 2004. The third fact is that I never worked on the glycosylation papers directly. My analysis came completely from published papers. When I presented my analysis of the now retracted papers back in the autumn of 2006, I did so against the accumulated backdrop of a minimum of 5-10 vacuous post-doc years from my fellow friends and coworkers. Again, this was in 2006. (In the UK, it would cost ~£600,000 to fund 5 post-doc years.) I am often asked how was I so smart to be able to figure out a problem that escaped so many other, much smarter, people. The answer, as with many scientific breakthroughs, was one of serendipity. While recovering in the hospital after breaking my leg during the last World Cup, two pages from two disparate reports ended-up next to each on my hospital bed. A child would have noticed the similarities. When I did go and present my analysis, I did so repeatedly, and I did so to no fewer than 30 former and current Scripps co-workers. These individuals would go on to tell other individuals. By my assessment, the flaws in these two retracted papers were already pervasive in the community by the end of 2006. I would continue to present the same analysis at international conferences over 2007-08. In regards to the JBC paper that we did eventually get published, the manuscript began its life as a communication to The Journal of American Chemical Society, which was submitted on February 7, 2009. This initial manuscript was rejected without review. Similar treatment would befall our manuscripts at 6 other journals. I would have also hoped that the key scientific aspects of my 2006 analysis, or our 2009 JBC paper, would have been found to be more in-line with Nature's mission of reporting ??issues concerning science.? This is because few other retracted papers can lay claim to monetary values approaching half a billion dollars, and therefore it is my opinion that Science and Nature?s readers, many of whom referee important papers, would have benefited more from an in-depth analysis of these retracted papers. Specifically, what was the key evidence offered that the referees from two of our top journals found so seductive. Since this has not been the case, it seems only right to again attempt to resolve such scientific issues in the scientific literature.
Avatar of: anonymous poster

anonymous poster

Posts: 5

July 7, 2010

The way that this issue was treated was standard smearing of the whistleblower.

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