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Published online 9 May 2008 | 453, 275-278 (2008) | doi:10.1038/453275a
News Feature
Chemistry: Designer debacle
A high-profile scientist, a graduate student and two major retractions. Erika Check Hayden reports on a case that has rocked the chemistry community.
When Mary Dwyer was looking for a doctoral adviser, Homme Hellinga was her first choice. A biochemist at Duke University Medical Center in Durham, North Carolina, Hellinga had ground-breaking ideas and an exciting research programme.
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What a thorough, well-written article! My concern, especially as emphasized in the accompanying editorial, is the "no discernable benefit to his own career" earned by Dr. Richard's work leading to Hellinga's retractions. The lack of credit given to those who reproduce (or refute) others' work directly leads to the perverse incentive to rush to publish work first, often with data that is shoddy at best, fraudulent at worst. Incentives in the world of science need to be modified - less of a skew toward the first to publish a new finding, more credit given to those who reproduce or refute others' findings. Sincerely, Noam Y. Harel, New Haven, CT, USA
Isn't it lovely how this big, powerful, famous professor is willing to take all the credit and accolades associated with hot papers coming out of his lab, but then tries to distance himself and blame the student when some of those same papers turn out to be bunk. I'm sorry, but he can't have it both ways. Hellinga must now try to rebuild his tarnished reputation or risk ostracism and possible punishment of the likes experienced by Hwang and Schön. First step: he needs to come clean instead of throwing his students under the bus. Second step: he should make financial amends to Dr. Richard by using some of his apparently large financing to cover the costs incurred by Dr. Richard in his goose chase. In science, reputation is everything. If Dwyer plans to stay in the field, she may have to sue Hellinga for libel in order to restore her reputation. I think she also owes the community an explanation for the unexplained results highlighted in this article. -Alex Tobias
Retraction of What??? ----- I fully agree with the Editorial by Nature that "Retracted papers require a thorough explanation of what went wrong in the experiments". As a matter of fact, this view echoes well my PUBLISHED opinion that "Retractions should focus on the content rather than the conduct" (http://im1.biz/albums/userpics/10001/V5_I3_A13_Retraction.htm or http://im1.biz/albums/userpics/10001/V5_I3_A13_Retraction.pdf ).///// If retractions do not answer the question of What is retracted or what part of the paper is retracted, the retraction will serve no purpose of cleaning up scientific literature. ///// Shi V. Liu (SVL@logibio.com; http://im1.biz; http://blog.sina.com.cn/im1)
Avoiding retraction-added confusion to science!!! ----- In another PUBLICATION entitled "Retraction of What? And Why?" (http://im1.biz/albums/userpics/10001/TW2007V2N2A19_RetractionWhat.htm or http://im1.biz/albums/userpics/10001/TW2007V2N2A19_RetractionWhat.pdf ), I stated that "Science is harming the public twice: one for publishing a flawed “discovery†and second for adding more confusion on what the truth should be. "//// As to this new retraction of another Science paper, I am still confused with the content of retraction. The statement in Nature Editorial that "All has ended happily" because (?) a third group published research showing that rational enzyme design really is possible" further confused me as to whether Hellinga indeed has enabled "the field marching forward in triumph"./// By quickly glancing the referred new publication representing the "third group" I felt that the new studies may just proved rational design works for creating some other enzymes but has noting to do with proving Hellinga's (irrational) design that produced no (really) active enzyme. Am I right in this understanding? //// Shi V. Liu (SVL@logibio.com; http://im1.biz; http://blog.sina.com.cn/im1)
Limiting retraction destruction of credible and hardworking young scientists!!! ----- It happens so often that, after cannot contain the errors anymore in the once glory publication that earned a great credit (for the "principle" investigator), the corresponding author will "bravely" retract the paper. It also happens very often that the corresponding author will not take any (real) co-responsibility for the now flawed or even fraud publication because (only now) the true principle investigator is not the corresponding author. The actual role played by the formally believed "principle" investigator may be limited only to the (roughly) design of experiment and/or writing of the (revised or final version of) manuscript. Sometimes I actually read the only contribution of a corresponding author (as disclosed in the publication) is getting the funding for the research which was designed even by other authors (I am wondering how the grant was awarded to such an investigation that might not even be the part of a proposal).//// So my serious concern is that, when corresponding author behaves in such an irresponsible way, what more damage may have done to scientific community? Will the destruction of hardworking bright young scientists be a loss to scientific community???? I am glad that Mary Dwyer survived (I hope so) this retraction destruction. However, what about the scientific career of other credible young scientists whose reputation was ruined by their mentors just because they did some once-considered "excellent" work but actually received no credit but only blames because the work is allegedly "not reproducible"???? I wish scientific community to re-examine the following still unresolved cases because the scientific career of the true principle investigator is severely jeopardized by the "big boss" of the project.//// Nobel prizewinner's paper retracted (http://www.nature.com/news/2008/080305/full/452013a.html) //////// Science retracts major Arabidopsis paper (http://www.the-scientist.com/templates/trackable/display/news.jsp?type=news&o_url=news/home/53081&id=53081 ) //// Shi V. Liu (SVL@logibio.com; http://im1.biz; http://blog.sina.com.cn/im1)
Nature's blogging gives real scientists a hope for justice///////// I must admit that Nature is the best among the worst "top" journals because at least it allows some opinions be expressed in limited freedom. I hope this window for freedom and opportunity for justice will remain open and open much wider.//// Now I wish someone will pick up this "dead" topic that "Nilsson and Science owe public more answers than a simple retraction" (http://im1.biz/albums/userpics/10001/SE2007V2N2A1_Nilsson.htm or http://im1.biz/albums/userpics/10001/SE2007V2N2A1_Nilsson.pdf ).///// Shi V. Liu (SVL@logibio.com; http://im1.biz; http://blog.sina.com.cn/im1)
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A whistleblower was actually condemned!!!! As the most outspoken scientist against high-level misconduct in science (editor in chief of Scientific Ethics, the only scientific journal dedicated to this topic and is an open-access and open-review journal at http://im1.biz), I started a series PUBLIC criticisms on the hypes and even misrepresentations in the high-profile publications on iPS cells (http://im1.biz/Cloning.htm; http://www.nature.com/news/2008/080116/full/451229a.html ). However, my valid criticisms and brave efforts were received poorly by all the "top" journals so far. Not only none of these journals rejected my credible submission of criticisms, Nature even ridiculed me by allowing a person of a group with a pseudo-name of "E E" to called me as "mad man" (http://www.nature.com/news/2008/080326/full/452406a.html).//// Now one of my criticisms is published even in a mainstream journal Stem Cells and Development (http://www.liebertonline.com/doi/abs/10.1089/scd.2008.0062 ). But my views are still ignored by the "top" journals.//// Why????? Shi V. Liu (SVL@logibio.com; http://im1.biz; http://blog.sina.com.cn/im1)
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I think Noam makes a very good point. Many graduate students have "died" in the trenches while trying to reproduce work which is suspect. And sometimes, even if the work is not suspect, inadequate information is published, leading to problems in replication.
There is now at least one journal where the Dr Richard's team data can be published - the BMC Research Notes, which is as well an open access journal. It is the best interest of the scientific community to have the Dr Richard's Lab results published. It is as well of best interest to find out if Dr Hellinga is responsible for the fraud data. Since the science is going more and more open to society such shaming episodes should be cleared with tough will. It is not in house problem anymore - the non scholars are interested in science and many science journalist are researcher as well. The society is really informed and the scientific community must react accordingly. If not, we will lose the confidence and the support we need. Sincerely, Yassen Pekounov, Researcher & freelancer scientific writer, Sofia, Bulgaria
Cell should retract invalid claims in its high-profile iPS publication!!! ----- In 2006 Cell published the first research report on iPS cells (Takahashi and Yamanaka, Cell 126: 663, 2006 ) with a Commentary (Rodolfa and Eggan, Cell 126: 652, 2006) clearly stated that "Takahashi and Yamanaka have successfully reprogrammed terminally differentiated cells to a pluripotent state." This claim not only led to a seismic shift in stem cell research but also led to the conceptual construction of the first biological airplane.//// However, did Yamanaka et al. really achieved the direct reprogramming of a terminally differentiated cells to a pluripotent state?///// No!!!!! In his formal response (on behalf of all the coauthors) to my scientific criticisms (http://im1.biz/Cloning.htm), Yamanaka stated that "We have never claimed that we generated iPS cells from terminally differentiated cells. We agree that the origin of iPS cells may be tissue stem or progenitor cells co-existing in fibroblast cultures."//// In his recent publication in Science (http://www.sciencemag.org/cgi/content/abstract/1154884) , Yamanaka also admitted that "the cell origins and molecular mechanisms of iPS cell induction remain elusive". The new claim of proving induction of iPS cells from differentiated cells as reported in this recent Science paper was not only rejected by my analysis of the data (http://im1.biz/Cloning.htm) but also echoed by Jaenisch et al. in his very recent Cell paper (Cell 133:250-264, 2008)./// Jaenisch et al. stated: "as albumin gene expression marks heterogeneous cells populations in the liver in addition to hepatocytes, including oval cells that play an important role in liver regeneration and might serve as adult liver stem cells, the question of reprogramming terminally differentiated cells remains unresolved."///// Thus, it is very clear that Yamanaka et al. so far have not proven that they can induce pluripotent stem cells from truly differentiated cells. Then why didn’t Cell retract those high-profile iPS publications which have generated some very high but unrealistic hypes??? //// Shi V. Liu (SVL@logibio.com; http://im1.biz; http://blog.sina.com.cn/im1)
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In my opinion the article presents Dwyer too much as a victim. Of course Hellinga is to blaim about submitting "quick and dirty" work and he should never have accuused her. However, what about Dwyer! She did not object when the paper was submitted and did not say anything about it over the last 3 years. Moreover, she probably got a lot of credit (and probably her new position) due to that paper. Now, after the paper is retracted she is complaining about her former boss and the presure he put on her. Well, she too late! And statements about beeing warned not to work for that prof already in 2000 have nothing to do with this case at all.
All authors are responsible for the mistakes in a co-authored publication but those who gained the main credit also need to pay the main credit back by taking main responsibility./// How much power that Dwyer had in overpowering the order of her "boss"? Would she be willing to loss her position right away for being honest or be betting off in hoping for a lucky end even if she knew her data was shaky?/// When an experienced "authority" told an inexperienced student that her data was good enough for publication and even good enough for targeting a "top" journal, how many junior researchers would not jump onto that bandwagon, especially knowing that the "boss" will handle all the spotlight issues?/// Be reasonable and also be logical!!!/// I guess there are many "Dwyers" out there doing the same things under the pressure of the "principle" investigators./// You asked for it (the "good" data for supportting your hypothesis in your money-winning grant), here it is. ------- Shi V. Liu (SVL@logibio.com; http://im1.biz; http://blog.sina.com.cn/im1)
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As these bloggers suggest, the bigger story here is how the science press, Nature included, has let down the scientific community. As in other cases of retractions, rather than thoughtfully discussing the actual science, the press covering this story has appealed to prurient themes like "fraud". When it is finished with these, the science press has focused on "contest" themes, asking who next will be the first to design an enzyme, now that the trophy no longer belongs to Hellinga. Missing is what is interesting to the scientist:What is the current state of biocomputation? At its current state, is it reasonable to expect biocomputation to actually design enzymes? What should be done next to advance biocomputation? This article, for example, does not move the ball forward on any of the issues of interest to scientist. Instead, it suggests that a team led by David Baker might claim this (mythical) trophy. That paper reports that different computational tools helped design a different enzyme, one catalyzing a retroaldol reaction via an imine intermediate. Nature's readers need to know that non-computational heuristics from physical organic chemistry have long supported enzyme design, including enzymes using imines to catalyze transformations similar to retroaldol reactions. In cases from the last decade, Kirkwood-Westheimer theory (which models acid-base properties of charged molecules), Brønsted theory (which models dehydration reactions), and Coulomb's law (which models substrate binding) were applied by human intuition without computer code. What makes recent work interesting is not that numerical computation has delivered better enzymes than physical organic heuristics; it has not, comparing the rates of the designed enzymes. Rather, the latest work is interesting because ANY evidence that computation might displace intuition in chemistry would indicate a major advance. This displacement would also suggest that numerical simulation is making real progress towards meeting some of its own challenges. Simulations have long been defeated by the complexity of "simple" problems in chemistry, such as the solubility of salt in water, the packing of organic crystals, and the melting of ice. These are, however, foundational elements closely tied to protein folding and enzymic catalysis; they must be simulated correctly to design enzymes de novo. Has such progress been achieved? As the retracted paper shows, it is hard to tell, especially if the computation is reported as part of the solution to a "big problem". Unfortunately, science funds and publishes investigations purporting solutions to "big problems" over those developing elements of those solutions. Hellinga, for example, received the NIH "Pioneer Award" by claiming a numerical tool to model enzyme-substrate interactions, not a tool to model the solubilities of salts (even though the second is integral to the first). This example therefore nicely illustrates the paradox today facing computational biochemistry. Much foundational work remains to be done to obtain numerical tools able to design complex systems (including enzymes); the value of these tools will be obvious if they model solubility, crystal packing, and melting ice. But this work will remain undervalued as long as it faces claims that "big problems" can be solved without it. A decade ago, the “Critical Assessment of Structure Prediction†project set out to evaluate claims that numerical tools could predict protein folds. CASP showed that numerical predictions were not necessarily better than predictions from computer-assisted human application of physical organic and evolutionary heuristics. A CASP-like project might now be useful for enzyme design.