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DBL%20Hendrix%20small.png College chemistry, 1983

Derek Lowe The 2002 Model

Dbl%20new%20portrait%20B%26W.png After 10 years of blogging. . .

Derek Lowe, an Arkansan by birth, got his BA from Hendrix College and his PhD in organic chemistry from Duke before spending time in Germany on a Humboldt Fellowship on his post-doc. He's worked for several major pharmaceutical companies since 1989 on drug discovery projects against schizophrenia, Alzheimer's, diabetes, osteoporosis and other diseases. To contact Derek email him directly: derekb.lowe@gmail.com Twitter: Dereklowe

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January 20, 2014

A Long Fight Over Allegations of Fraud

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Posted by Derek

Here's a long article from the Raleigh News and Observer (part one and part two) on the Eaton/Feldheim/Franzen dispute in nanoparticles, which some readers may already be familiar with (I haven't covered it on the blog myself). The articles are clearly driven by Franzen's continued belief that research fraud has been committed, and the paper makes the most of it.

The original 2004 publication in Science claimed that RNA solutions could influence the crystal form of palladium nanoparticles, which opened up the possibility of applying the tools of molecular biology to catalysts and other inorganic chemistry applications. Two more papers in JACS extended this to platinum and looked at in vitro evolutionary experiments. But even by 2005, Franzen's lab (who had been asked to join the collaboration between Eaton and Feldheim, who were now at Colorado and a startup company) was generating disturbing data: the original hexagonal crystals (a very strange and interesting form for palladium) weren't pure palladium at all - on an elemental basis, they were mostly carbon. (Later work showed that they were unstable crystals of (roughly) Pd(dba)3, with solvated THF. And they were produced just as well in the negative control experiments, with no RNA added at all.

N. C. State investigated the matter, and the committee agreed that the results were spurious. But they found Feldheim guilty of sloppy work, rather than fraud, saying he should have checked things out more thoroughly. Franzen continued to feel as if justice hadn't been done, though:

In fall 2009, he spent $1,334 of his own money to hire Mike Tadych, a Raleigh lawyer who specializes in public records law and who has represented The News & Observer. In 2010, the university relented and allowed Franzen into the room where the investigation records were locked away.

Franzen found the lab notebooks, which track experiments and results. As he turned the pages, he recognized that Gugliotti kept a thorough and well-organized record.

“I found an open-and-shut case of research fraud,” Franzen said.

The aqueous solution mentioned in the Science article? The experiments routinely used 50 percent solvent. The experiments only produced the hexagonal crystals when there was a high level of solvent, typically 50 percent or more. It was the solvent creating the hexagonal crystals, not the RNA.

On Page 43 of notebook 3, Franzen found what he called a “smoking gun.”

(Graduate student Lina) Gugliotti had pasted four images of hexagonal crystals, ragged around the edges. The particles were degrading at room temperature. The same degradation was present in other samples, she noted.

The Science paper claimed the RNA-templated crystals were formed in aqueous solution with 5% THF and were stable. NC State apparently offered to revoke Gugliotti's doctorate (and another from the group), but the article says that the chemistry faculty objected, saying that the professors involved should be penalized, not the students. The university isn't commenting, saying that an investigation by the NSF is still ongoing, but Franzen points out that it's been going on for five years now, a delay that has probably set a record. He's published several papers characterizing the palladium "nanocrystals", though, including this recent one with one of Eaton and Feldheim's former collaborators and co-authors. And there the matter stands.

It's interesting that Franzen pursued this all the way to the newspaper (known when I Iived in North Carolina by its traditional nickname of the Nuisance and Disturber). He's clearly upset at having joined what looked like an important and fruitful avenue of research, only to find out - rather quickly - that it was based on sloppy, poorly-characterized results. And I think what really has him furious is that the originators of the idea (Feldheim and Eaton) have tried, all these years, to carry on as if nothing was wrong.

I think, though, that Franzen is having his revenge whether he realizes it or not. It's coming up on ten years now since the original RNA nanocrystal paper. If this work were going to lead somewhere, you'd think that it would have led somewhere by now. But it doesn't seem to be. The whole point of the molecular-biology-meets-materials-science aspect of this idea was that it would allow a wide variety of new materials to be made quickly, and from the looks of things, that just hasn't happened. I'll bet that if you went back and looked up the 2005 grant application for the Keck foundation that Eaton, Feldheim (and at the time, Franzen) wrote up, it would read like an alternate-history science fiction story by now.

Comments (14) + TrackBacks (0) | Category: Chemical News | Press Coverage | The Dark Side | The Scientific Literature


COMMENTS

1. exGlaxoid on January 20, 2014 9:45 AM writes...

Just finished the second part of the article. It does appear that the original work was based on a few poor experiments and a rush to publish.

Unfortunately, that is what the current mindset of publish or perish and hurry to submit grant proposals creates, as people want to publish data before the proper follow up and verification experiments can be done. In some cases, that is just due to being in a hurry to get tenure or more funding, in some cases, due to blind faith in a hypothesis, and in many due to financial gains from having the research progress.

The sad part is that once Franzen realized the issues, he would have been personally much better off to simply walk away, rather than to try to correct the errors, given the treatment that most people get when trying to undo published science.

Permalink to Comment

2. anonymous on January 20, 2014 9:54 AM writes...

Since this research spun off a startup company, to what degree might the original (allegedly sloppy) researchers be liable to investors?

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3. Anonymous on January 20, 2014 12:50 PM writes...

@2: Most investors require that founders sign an investment agreement with some statement that "the founders are not aware of any issues or facts that could cause problems, except for those specifically disclosed in due diligence". So if the investors can prove this was intentional fraud, not just an innocent mistake or oversight that the founders were not aware of, then the investors could sue to get their investment back.

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4. Chemjobber on January 20, 2014 1:06 PM writes...

I think it's interesting that more hasn't been heard from the NSF's research integrity folks. I wonder how different it would be if it had been NIH funds and the folks at ORI would've been involved.

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5. Anonymous on January 20, 2014 3:15 PM writes...

Colorado alum. Was around when Eaton got hired and this finding was the heart of his job talk. Later, a year or so after he got going at CU, there were whispers of a fraud investigation but I never heard any details. This was mainly because I tended to be out of the gossip loop in general but also because the whole thing was kept very quiet as it had the potential to be extremely embarrassing.

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6. Anonymous on January 20, 2014 6:35 PM writes...

@5: "Later, a year or so after he got going at CU, there were whispers of a fraud investigation but I never heard any details. This was mainly because I tended to be out of the gossip loop in general ..."

So instead you prefer to spread gossip without knowing the details???

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7. a on January 20, 2014 7:58 PM writes...

Juicy!

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8. Pd2(dba)3 on January 20, 2014 8:31 PM writes...

I'm disappointed I'm not getting a fair shake...RNA...meh...don't need none of that.

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9. anon electrochemist on January 20, 2014 9:52 PM writes...

The DNA and peptide versions of this are very real. It remains the system of choice when exquisite control over shape is required. Unfortunately, it's over-the-top expensive, and we simply don't have many applications that require single crystal nanoparticles with such well-defined geometries. Most catalysis applications don't require specific facets to be exposed for selectivity, although they certainly have different binding/activity. Active surface area via particle size tends to be more important.

If sensors and optical materials continue to move towards metal nanocrystals this research will have serious impact.

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10. cookingwithsolvents on January 20, 2014 9:55 PM writes...

I'm more of a molecular person myself but I don't think too many of the 'oldER guard' folks ever believed that stuff too much. That said, you can get all kinds of effects on particles, etc. by using different additives, etc. Heterogeneous catalyst people have been doing this for ages. They weren't impressed, either. Glad the faculty stuck up for the student, though the student should have been trained (and known) to index the diffraction pattern.

That last paper from Particle that shows the beam-induced NP formation is awesome. No time to read in detail now but it's going on top of my 'to read ' pile. As an aside, there are a lot of other times that the beam has done stuff like this. Crystallizing things is the "classic" one with amorphous materials. Zoom in..hey, it's crystalline! Zoom out, move...heyyyyy... :)

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11. Anonymous on January 21, 2014 12:20 AM writes...

@6: Not sure what you're on about, given that the investigation clearly actually happened. Of course, eight years ago, when the buzz went up around the department, I had no idea if there was an investigation or not and what the conclusion was. At the time, I figured that if something big went down we'd all be informed but nothing big went down. Therefore, until today, I assumed that, whatever it was, the conclusions of the inquiry came far short of fraud. Apparently, that's why eight years later Frazen is still grinding his axe.

Using heavily modified RNA aptamers to mediate nanocrystal formation flopped. Using heavily modified RNA or DNA aptamers in general did not.

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12. paperclip on January 21, 2014 3:03 PM writes...

"...the chemistry faculty objected, saying that the professors involved should be penalized, not the students."

That certainly reads like an alternative history-science fiction story.

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13. matt on January 21, 2014 6:54 PM writes...

@paperclip #12: maybe that's because the doctoral student was a professor now and was therefore accorded the rights and privileges thereunto pertaining?

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14. Mica on January 23, 2014 9:35 AM writes...

@13: Perhaps more to do with the assumption that the student is not guilty for faulty interpretation? I.e., as I understood (might be mistaken), the doctoral student did not obviously fake data, thus interpretation of provided data and request to run controls would be even more assumed to be the responsibility of senior investigators?

Very often situations occur in which very junior investigators come all excited about "promising" results that end up being nothing. I would give her benefit of doubt that she came and got senior investigators so excited that they forgot to run controls. Once published (reviewers!), the delay to correct "because we were correct in what we wanted to do, so one more experiment will prove us...and...and.. Newton did it as well..." took over.

Or as in politics: It's not the initial error -- it's the attempt to cover it up that usually gets them.

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