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Volume 94 Issue 8 | pp. 37-38 | Latest News
Web Date: February 15, 2016

Nanoparticle Synthesis Paper Retracted After 12 Years

Science withdraws paper after NSF finds poor research practices and data misrepresentation
Department: Science & Technology
News Channels: Biological SCENE, Materials SCENE, Nano SCENE
Keywords: misconduct, nanoparticles, RNA, retraction
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CONVERSION
Nanoparticle formation process reported in the 2004 Science paper by Eaton, Feldheim, and Gugliotti.
Credit: Adapted from Science

Nearly 12 years after Science published a nanoparticle synthesis paper, the journal has decided to retract it. The withdrawal is in response to a National Science Foundation report that found the paper’s authors used poor research practices and misrepresented data, although the report also concluded that they did not engage in misconduct.

The paper, which is on RNA-mediated formation of palladium nanoparticles, was written by Bruce E. Eaton, Daniel L. Feldheim, and grad student Lina Gugliotti—all of whom were at North Carolina State University (NCSU) when it was published (Science 2004, DOI: 10.1126/science.1095678). Eaton and Feldheim are now at the University of Colorado.

The team reported in 2004 that putting select RNA sequences into an aqueous solution of tris(dibenzylideneacetone)palladium(0) caused hexagonal-shaped inorganic Pd nanoparticles to form. The researchers concluded that the RNA catalyzed the process. C&EN wrote a story about the work at the time (April 19, 2004, page 9), asking Gerald F. Joyce, of Scripps Research Institute California, to provide expert comment. Joyce was enthusiastic about the results: “We now realize that RNA is adept at synthesizing inorganic materials, and this discovery takes the field of RNA-directed evolution in a whole new direction.”

The development instead veered off in an unexpected direction. A group led by NCSU physical chemist and biophysicist Stefan Franzen, a one-time collaborator of Feldheim’s and Eaton’s, tried to better understand the RNA-mediated process but couldn’t replicate the work. Franzen’s team found that the reaction caused hexagonal particles to form but that the shapes contained carbon and thus were not strictly inorganic Pd nanoparticles. The researchers also determined that RNA didn’t seem to play any role in the particles’ formation. Franzen says he discussed his observations with Feldheim and Gugliotti and also tried to communicate with Eaton about them. Eaton says Franzen never contacted him at this time or later on. In any case, the researchers weren’t able to resolve the matter.

In 2006, an NCSU administrator suggested that the seeming irreproducibility of the research be evaluated as a possible case of scientific misconduct. The resulting investigation concluded in a 2008 report that electron microscopy experiments to study particle formation, shape, and composition had not been carried out correctly. It also concluded that solution conditions needed to solubilize the organopalladium starting material had not been described properly in the Science paper. The report charged Feldheim, Eaton, and Gugliotti with negligence but not with research misconduct. The University of Colorado also investigated the matter, concluding that there was nothing wrong with the study’s methodology or with the way the Science paper was written, a far different conclusion than NCSU’s. Meanwhile, NSF launched its own investigation.

At one point during this period, Franzen asked Eaton and Feldheim to cooperate on a technical note to Science about the problems, but they declined, Eaton says, because “the note was full of technical false statements” and the request “was posed as an ultimatum.” So Franzen and coworkers instead ended up airing the problems in a September 2008 letter to Science. In a reply, Feldheim, Eaton, and Gugliotti claimed that a redo of the electron microscopy work showed that the original findings had been valid and that they had made the organopalladium reagent soluble by adding a cosolvent, although that information hadn’t been included explicitly in the original paper.

A Long Road

The dispute over a Science paper has been raging for 12 years.

May 2004: Eaton, Feldheim, and Gugliotti publish their Science paper.

Dec. 2006: NCSU launches its investigation into the research.

June 2008: NCSU concludes its investigation.

Sept. 2008: NSF launches its investigation.

Sept. 2008: Franzen and coworkers submit letter to Science, surfacing problems with the original work.

Aug. 2010: Feldheim, Eaton, and coworkers publish a Journal of Materials Chemistry paper that repeated the 2004 work and confirmed its findings.

Feb. 2013: Franzen, De Yoreo, and coworkers publish Particle & Particle Systems Characterization paper concluding that the original work was flawed and that RNA does not catalyze the formation of inorganic Pd particles.

Sept. 2013: NSF OIG posts preliminary findings online.

Oct. 2015: NSF posts final decision memo online.

Feb. 2016: Science retracts the 2004 paper.

Later on, the Colorado group repeated the complete 2004 study and reported in a scientific paper having confirmed all their original findings (J. Mater. Chem. 2010, DOI: 10.1039/c0jm02050h). But Franzen subsequently published a Technical Comment in the same journal (J. Mater. Chem. 2013, DOI: 10.1039/c3tb20820f) that critiqued the methodology and findings of the 2010 paper. Franzen; materials scientist James J. De Yoreo, then at Lawrence Berkeley National Laboratory; and coworkers also reported in another journal (Part. Part. Syst. Charact. 2013, DOI: 10.1002/ppsc.201200114) that the particles made by the process described by Eaton and Feldheim are nothing more than aggregates of the starting material. This is similar to how snowflakes form, a process that doesn’t require RNA to proceed, Franzen says.

Preliminary findings of NSF’s investigation, posted online in 2013 by the agency’s Office of Inspector General (OIG), were that the 2004 Science study had been conducted without due care, that the findings were not fully supported by the paper’s data, and that the authors had negligently failed to correct errors. Eaton tells C&EN that the OIG report contained 11 incorrect statements and that he and his coworkers responded to it by pointing out “documented facts proving the report was false.”

NSF’s recently issued final decision memo suggests the agency’s OIG did not find those arguments persuasive. In it, NSF’s OIG stated that Eaton, Feldheim, and Gugliotti had “recklessly falsified research data” and had departed significantly from accepted practices. The OIG recommended a finding of research misconduct, that a letter of reprimand be issued to the researchers, and that they publish a correction in Science.

NSF eventually declined to accept its OIG’s recommendation for a finding of research misconduct. But the agency did conclude “that the subjects’ actions were a significant departure from standard research practices.” It issued the letter of reprimand and declared the subjects ineligible for NSF funding until they submitted a correction to Science.

Editor-in-Chief Marcia McNutt says Feldheim did submit the required correction but that the editors at Science “do not think a correction is appropriate given the concerns” raised by the OIG report. The journal retracted the paper instead (Science 2016, DOI: 10.1126/science.351.6273.569-a). Eaton says he corresponded extensively with McNutt in an effort to get her to rethink the retraction decision, but McNutt insisted retraction was the appropriate move. Eaton and Feldheim did not agree to the retraction. “I truly know that RNA-mediated formation of nanoparticles does reproduce, as reported in Science and the other publications,” Eaton says.

Franzen says the process hasn’t been easy or pleasant. “It has plagued me for the last nine years. I’ve been investigated, I’ve been threatened by lawyers, and I’ve been charged with stealing samples. But I didn’t do anything wrong, and I have been exonerated of everything.”

He insists Gugliotti is actually blameless because her lab work was flawless, her lab notes were complete, and she didn’t write the 2004 Science paper. C&EN was unable to locate Gugliotti by press time.

Asked to comment on whether issues with the 2004 paper have adversely affected related scientific research, Joyce said: “Science is a self-correcting process—even 12 years after the fact.”

 
Chemical & Engineering News
ISSN 0009-2347
Copyright © American Chemical Society
Comments
Sasha  (February 15, 2016 8:30 PM)
I'm sharing this with my students to encourage them to keep neater lab notebooks - and as a reminder to myself.
pam  (February 16, 2016 1:09 PM)
I am intrigued by the statements concerning Gugliotti attributed to Franzen at the end of this article. This gets to the heart of the issue of responsible authorship. How can someone be an author, have their name appear on an article and not participate in the writing, editing, and review process?
David Hanson  (February 17, 2016 4:44 PM)
Pam, I understand your perspective. Here are three answers to the question you pose.
1) I am a beginning graduate student. I work really hard and collect lots of data. My adviser and some of her colleagues write a paper and give me a draft. It describes what I have done and presents the data accurately, but I really have no clue about some of the other things they say. I do not want to reveal my ignorance to them, so I keep quiet. Maybe not good, but that is how it might occur.
2) I am a senior scientist visiting and working with another group outside my area of expertise. I collect lots of data, have to leave, return to my home institution, and run my group of several graduate students. The group I visited write papers based on my data, I really have no time or the expertise to oversee what they say. I rely on their expertise and integrity. I think my name should be on the papers to recognize my contributions. I am even happy being listed as the last author not the primary author.
3) I am involved with the team of hundreds that detected gravity waves. My area of expertise is small but crucial. I am not going to confront the leaders regarding their conclusions that I don't understand. I am grateful my name is on the paper. Should my name be removed, and my years of hard work go unrecognized, because I don't have a complete understanding? And if the analysis is fraudulent, am I responsible? I didn't do the analysis, I only made one of the interferometers work.
Kelly  (February 17, 2016 10:15 PM)
It's standard practice to credit grad students as second or third authors. Usually the first author listed actually does the writing, but the science is usually done by a team. Since in academia we keep score by how many publications you have authored, it's expected that junior members of the team will be given second or third authorship on projects they take a large role in, even if they haven't designed the experiment or written it up in a paper. The comment that the grad student just worked in the lab and didn't do any of the write-up is completely believable. We all have to start somewhere!
(Source: 5 years earning my PhD in Physical Chemistry)
Hugo F. Franzen, Prof/ Emeritus, iowaa State Univ.  (February 16, 2016 1:16 PM)
I have been in on Stefan Franzen's involvement in this controversy from the outset, in large part because Stefan is my son, but also because I am a physical Chemist with over fifty years of experience in Solid State Chemistry. My overall conclusion is that the scientific community is ill equipped to deal with scientific malfeasance. From the beginning I could see that the concept of the cartoon of the type shown in your article represents a trivial approach to a notion (RNA mediated (whatever that means!) synthesis of nanocrystals). The notion is on the surface so farfetched that its demonstration would require excellent, careful experimentation. The reported experimental work, instead, provided nonsensical interpretations of a few diffraction maxima from a source that was not even superficially characterized, claims of solubility that defy expectations and, since Stefan's J. Chem. Educ. article, are thoroughly known, and XPS which showed large carbon signals. When truly excellent diffraction was done in collaboration with DeYoreo it demonstrated what was already known, namely that the "nanocrystals" were, as was expected by any experienced chemist, simply starting material precipitated out by the addition of water to the THF solution. That this sorry case was dragged out by legal and behind the scenes maneuvering over 9 years involving personnel from reputable journals and the Univ. of Colo. is indicative of a grave shortcoming in the process of correcting scientific errors.
Hugo F. Franzen, Prof/ Emeritus, iowaa State Univ.  (February 16, 2016 1:16 PM)
I have been in on Stefan Franzen's involvement in this controversy from the outset, in large part because Stefan is my son, but also because I am a physical Chemist with over fifty years of experience in Solid State Chemistry. My overall conclusion is that the scientific community is ill equipped to deal with scientific malfeasance. From the beginning I could see that the concept of the cartoon of the type shown in your article represents a trivial approach to a notion (RNA mediated (whatever that means!) synthesis of nanocrystals). The notion is on the surface so farfetched that its demonstration would require excellent, careful experimentation. The reported experimental work, instead, provided nonsensical interpretations of a few diffraction maxima from a source that was not even superficially characterized, claims of solubility that defy expectations and, since Stefan's J. Chem. Educ. article, are thoroughly known, and XPS which showed large carbon signals. When truly excellent diffraction was done in collaboration with DeYoreo it demonstrated what was already known, namely that the "nanocrystals" were, as was expected by any experienced chemist, simply starting material precipitated out by the addition of water to the THF solution. That this sorry case was dragged out by legal and behind the scenes maneuvering over 9 years involving personnel from reputable journals and the Univ. of Colo. is indicative of a grave shortcoming in the process of correcting scientific errors.
DJ  (February 16, 2016 1:41 PM)
Most of the nanoparticle synthesis reports, very difficult to reproduce ! I myself struggled 6 months to reproduce a work based on siloxane nanowires and found it's impossible.
Donny  (February 17, 2016 3:12 PM)
I agree with DJ. As a graduate student researcher that wishes to harness the functionality of advanced nanomaterials for real applications, it is very frustrating and embarrassing when you can't simply reproduce a synthesis by following the protocol in high-impact literature reports. Sometimes you realize that you did actually synthesize the same products as the authors of the publication, but upon adequate characterization discover that the products are very different from what the authors claim. Then you can figure out how the authors were able to cherry pick minor species in data like electron micrographs and claim that the images represent the majority of nanoparticulate species. Many may also exclude critical spectroscopic characterizations that are contrary to their claim. Some cases are blatant misconduct like the "nano chopsticks" but most are just very sloppy, poisoning the research for the rest of us that work very hard to contribute pure scientific discoveries.
SK  (February 17, 2016 2:29 PM)
This story is nothing compared to colossal amount of dodgy results being dumped in slightly lower impact journals ..I am aware of a group of 'powerful' chemists who have been publishing partly fabricated data over last few decades. ...Good news however is that there are many legitimate scientists still alive.....
» Reply
David Mendenhall  (February 17, 2016 3:07 PM)
I would fault the reviewers of the original paper, who should have noticed the shortcomings and demanded additional work.
PA  (February 18, 2016 1:30 AM)
Whilst the reviewing should be an anonymous process while it is on-going, eventually Journals should associate the articles published online with not only the SI but also
(1) the reports of the reviewers,
(2) the answers to the reviewers provided by the authors and obviously
(3) the name and affiliation of the reviewers.

At least the contributions of the reviewers to the final manuscripts (and scientific community) would be acknowledged, reviewer-author networks would be made clear and could be overcome, the ratio of published to reviewed manuscripts per scientist could be assessed, fewer doubts over the quality of the reviewing process would emerge (or at least the intrinsic limits of peer-review would not be hidden and minimized), and finally no doubt that some reviewers would pay more attention when reading the manuscripts they commit to review, hence would probably build more constructive comments based less on the general reputation of a group or the fanciness of "new" results than on the scientific strength of the arguments and results which are presented.
There are plenty of advantages in presenting a manuscript along with its evaluations, and honestly, if the review of a manuscript is fair and sound (at least based on the knowledge available at the specific time the reviewing takes place), then there is no reason to hide this information, to expect the authors to be upset by a negative review, or to retaliate... potential retaliations would be neutralised by the very fact the reviews, replies and reviewers are eventually known from everyone, including the Journal editors and funding agencies.
The only caveat is obviously for the manuscripts which are "simply" rejected... but maybe that can be overcome by attributing a DOI or arXiv number to a manuscript before submitting it to a journal and then recording even though keeping the trail of submissions and reviews anonymous until the manuscript is eventually published.

In any case, it is obvious that the traditional peer-review process has reached its limits since marketing has become a key-concern of publishers, funding agencies and even scientists. The old-school approaches have lived and, to preserve what remains of trust in science, new ones should certainly be explored to at least identify their limits...
RK  (February 17, 2016 3:21 PM)
Alleged cases of scientific misconduct appear to be in the need for an independent instance to evaluate all facts and evidence brought forward. Presently,at a global level, not a single government has appointed this task to an official body or organisation. However, major patent offices such as the European Patent Office, the US Patent and Trademark Office and the Japan Patent Office are well equipped to carry out the duty of evaluating alleged scientific misconduct. Through their experience of evaluating patent applications, these organisations have build up an extensive amount of legal and scientific knowledge and experience, which would enable them to independently evaluate alleged cases of scientific misconduct.
Abdul-Hafiz  (February 17, 2016 3:28 PM)
I would simply call this knowledge and experience to me who is just at the entrance door to Chemistry B. Ed. It is lovely to find knowledge being screened, corrected and communicated with deep sense of responsibility. I am encouraged. I am strengthened in the belief that science is not dubious unverifiable claims but knowledge-based information.
Carol Smith Hemminger, Ph.D.  (February 17, 2016 6:20 PM)
I strongly agree with the comment of Hugo F. Franzen that there is "a grave shortcoming in the process of correcting scientific errors." My adviser at U.C. Berkeley published an article in Nature (1975, Vol 258, 580-583)just as I started my PhD research. I was not able to reproduce the published results, my first assignment before the plan to continue the work. During the ensuing months, while completing my advancement to candidacy requirements, I established root cause for the experimental discrepancies and determined that the published results were based on fatally flawed laboratory work. My adviser would not accept my results. He told me that the published work was the crowning achievement of his career and said that I was "inhuman and abominable" to attack the work. He declined to review my data. He approached the chairman of the Chemistry Department and asked him to request that I leave the department in spite of my NSF Fellowhip and successful advancement to PhD candidacy. This request was denied by the department after their review of my data, but I was instructed to abandon all further research in the area of dispute and to find a new dissertation topic with the help of a senior researcher or postdoctoral fellow in our group. My adviser declined to have all but minimal interactions with me, and the one paper that we jointly published (J. Catalysis, 1979, Vol 57, 426) was significantly edited and resubmitted without my input after one reviewer pointed out discrepancies with my adviser's earlier publications. I wrote up my "root cause" experiments for inclusion in my PhD thesis, which was ultimately signed off by my adviser and published. To my knowledge this is the only "correction" of the original publication. My adviser continued to promote the earlier work and deny that it had shortcomings, much less fatal flaws in the experiments. I retired in 2014 from a successful career of 37 years in surface analysis, failure analysis, and material science. I regret to say that I encountered other examples of flawed laboratory work that was overlooked or ignored, most commonly because the results were what the researcher expected or hoped to obtain. I have never seen similar examples when the data is contrary to the researcher's expectations and desires. I am confident that important scientific errors are eventually discovered and corrected. I believe that the retraction of the nanoparticle synthesis article is a positive indication that the scientific community is doing a better job of correcting error today than 40 years ago. But I surely hope that additional improvements will be realized by coming generations of scientists and engineers.
Kaoru Aou  (February 18, 2016 12:21 PM)
In reflection: I can only imagine the stress in academia of being sandwiched between the conflicting forces of scientific/personal integrity vs. the desire to get tenure/make a name for oneself. Without integrity and without reputation, a researcher's true value is zero -- actually, less than zero, if one's erroneous (or even fraudulent) work wastes the precious time of many graduate students and postdoctoral researchers, as one professor rightly pointed out when the Schön scandal emerged around 2002. Science can be eventually self-correcting, but often at the expense of precious time early in the careers of junior researchers - and only if that area of science has much activity, otherwise there have been concepts that have stood unchallenged for about a hundred years before being debunked (even after the emergence of modern science).
Hugo F. Franzen  (February 18, 2016 6:40 PM)
CSH I agree with all you say, I think it is important to also point out that in the case discussed in the above article the authors of the withdrawn paper were confronted with their misconceptions and misinterpretations at many times over the nine years that the controversy raged and given ample opportunity to correct the record. What they did instead was harass editors, university administrators and agency officials with threats of legal action. The job of lawyers is apparently to protect their clients regardless of the truth or whether they have any notion concerning the flaws in the experimental interpretation. A legalistic confrontation over a 9 year span exacts a toll on a whistleblower. There must be a better way!
Carol S. Hemminger, PhD  (February 24, 2016 5:45 PM)
Yes, Hugo, I absolutely agree with you on all the additional points you make here! Alas, it has been demonstrated by numerous researchers that people (including the best educated of scientists) are far more likely to believe in what they "like," regardless of supporting evidence than they are to accept facts that contradict what they like. It is extremely challenging to find a better way when fundamental human nature is at issue. I have reluctantly come to believe over the years that for some people it is essentially impossible for them to change their minds, once made up on their version of reality. They do not recognize that they are wrong or in any way being dishonest. It is a frightening example of the human capacity to get it wrong and then try to impose a distorted reality on all others.
Matt Warner  (March 1, 2016 11:57 AM)
I thoroughly agree with both of you; it is discouraging of course, but it is human nature to willfully believe what you like because you have invested time, energy, and ego in it. Human nature towards this end, after all, is one thing that science seeks to limit with the "self-correcting" and ongoing nature of research endeavors and peer review.

It is particularly discouraging for graduate students who have your kind of experience, Carol. An angry adviser or committee member has a lot of control over a young grad student's career should they be vindictive enough. I am reminded of an Emerson quote: "Let me never fall into the vulgar mistake of dreaming that I am persecuted when I am merely contradicted." The crux is, of course, that we usually encounter contradiction when we are emotionally attached to our position; this makes the realization of that quote much harder in practice sadly. You are very right--it is frightening, in many ways and particularly for younger or less connected researchers and students pressured to keep quiet.
James Demers  (February 24, 2016 5:24 PM)
In the long run, a scientist who confronts such problems in his own work head-on, and honestly works to set the record straight, gains much more in stature than he or she might lose from the temporary embarrassment of being wrong. You're going to be remembered not so much for having been wrong, but for how you dealt with it, and - eventually - for getting it right in the end. Going into denial and circling the wagons (and calling in lawyers to defend your position!) is precisely the wrong thing to do.
A good example of doing the right thing is Ronald Breslow's experience with fabricated data in 1986. Breslow investigated the matter, established the facts to his satisfaction, and did not hesitate to withdraw the three affected publications. If anything, the way he handled the affair enhanced his reputation, and his "being wrong" (if you can even call it that) has long been forgotten. Scientists caught a similar bind today should keep this lesson in mind.
Rich Styles  (March 4, 2016 10:28 AM)
My question is what will the institutions where these two fine examples of scientific integrity or lack there of be doing? Will the two scientists remain in their positions as the educators of our next generation of young scientists? Just a simple retraction of a manuscript is simply too lenient, and should come with penalties against everything from recieving funding to more agressive review of all futuer scientific publication.
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