Org Prep Daily

June 26, 2007

Faked Experiments

Filed under: industry life — milkshake @ 3:41 pm

When I came to US to join a small startup biotech company, my first assignment was to re-synthesize an active literature compound – a repulsive-looking peptidomimetic macrocycle. The compound was to be used in validating a new bioassay; the father of our young CEO needed the compound for his academic research. Our company “initiated a collaboration” with his group and that meant somebody ought to synthesize the stuff. Nobody volunteered but I was new and couldn’t protest – and my boss gushed that I could deliver the compound in six weeks. It took me over six moths of a full-time work – I was repeatedly offered reassignment to another project but I refused since I did not like to admit a failure. 

The SynLet. paper describing the synthesis that I was supposed to reproduce had no experimental procedures and the used starting material was not commercial or described in the literature. The only procedure for the starting material was in the PhD thesis of a person who did also the work on this published macrocycle. The procedures in the thesis were rather vague,  they never worked in my hands or in the hands of another chemist. I soon noticed that a hydrolytically-unstable silylated amine intermediate in the first step of a multistep sequence was formed in less than 50% NMR yield under conditions described in the thesis and the entire material was then immediately decomposed if the workup specified in the thesis was used. So I obtained this sensitive intermediate by alternate procedure, purified it by Kugelrohr distillation and took it to the next step – which also failed. Eventually I realized that the irreproducible thesis procedures were meant to be a “simplified” version of a known synthetic sequence. This original unmodified sequence worked exactly just as described so I  changed the protecting groups on the material in the end and then I could proceed with making the actual macrocycle.

I had a number of unpleasant surprises following the scheme and finally the key condensation reaction did not work at all. The reagents they “used” in the published scheme were different from the lit reference that they gave as a precedent for this step – and neither of these methods gave any trace of the desired product, on many attempts. I was getting desperate. Eventually I found a synthetic chemist whom I could talk to, from the group that published this irreproducible stuff. As I was describing my troubles he was laughing. It turns out that what they published was apparently an unmodified synthetic scheme from some grant proposal – with made-up yields. (They never retracted anything even after I alerted the PI about the problem. And they kept re-publishing this mess, once in PNAS then Synlett and later I think in Chem. Rev.)

My inside friend told me what kind of method they would use in such a case – different from the one published – so I was able to complete the molecule, convince my superiors that the problem was with the published baloney rather than with my freshly – minted MS degree from Eastern Europe. Looking back I think the PI in question knew from the beginning that his published work was irreproducible. But he could not afford to retract because he had to keep hyping the “technology platform” of his troubled small company in order to make the investors to continue pouring money in. (He also tried to plagiarize our methodology – I carelessly talked about my unpublished work and he published our results as his own, Cordova-style.) His company folded in the end.

sliva4b.jpg Credit: Jiri Sliva

7 Comments »

  1. Dear Milkshake,

    What a co-incidence! I worked for that very small company back in the early nineties! I for one can vouch for the complete accuracy of what you are reporting. Indeed, the procedures I used were often quite different from what was published by my co-workers. I too had to learn the hard-way (imagine the situation when you are actually working for the PI that published poor or out-right wrong procedures!). The whole thing was a disgrace, highly unethical to say the least. Rest assured that these shenanigans caught up to the poor folks who perpetrated them… in the end they always do, in one way or the other. Cheers! :)

    Comment by beenthere — June 26, 2007 @ 4:29 pm

  2. A person involved in this work later applied for a job with our company, the funny macrocycle synthetic scheme was the best piece in the research experience summary that she provided with her resume…
    You know, it is very difficult to expose a PI guy like this – I would have to spend extra few months on the project to have an iron-clad proof, re-synthesize material to get the NMRs of all intermediates. Both me and my superiors got quite tired of this waste-of-time affair. I received $10k raise and a promotion on account of this work so I was happy in the end. (Until they published my work- but that problem was causes by my carelesness; I left the company before it happened and I did not feel like the new fight was worth fighting).
    Chemistry world is quite small…
    Thank you for your note, beenthere.

    Comment by milkshake — June 26, 2007 @ 4:41 pm

  3. Such situations can probably be avoided if a strict and detailed requirements for describing experimental procedures would be developed by goverment. But it has much more to do besides unmasking cheating scientists :-)

    Comment by Zhenek — June 26, 2007 @ 4:57 pm

  4. Hey Milkshake,

    Send me an email. There are some things I want to share and ask you offline about your above mentioned post.

    Thanks,
    OGR

    Comment by OriginalGhostRider — June 27, 2007 @ 12:50 am

  5. At least you have a raise and a happy ending. Not at my place. A kid just applied for conversion, her work is spectacular. However, even if you work full-time, you can’t get all that done in time for the conversion window (12 months). Everyone knows that she did it in 24 months and with some help from her group. But,kid and her boss bended some rules and closed some eyes… She’s walking around like a proud puffed-up peacock right now.

    Comment by taitauwai — July 3, 2007 @ 8:09 pm

  6. Propagating an urban myth? Cited the paper.

    Comment by tandemmovements — July 8, 2007 @ 11:13 am

  7. Please give me a break, tandem-movements. People who participated know the details and the story is instantly recognizable to them. The name of the professor is not too important for the rest – his reputation is not tremendous anyway and I doubt he will ever get money for another company. Also, I have no time for getting sued.

    The description of their group that I got from that Czech fellow you are hinting at was not accurate in detail (I deleted his unfair broadside on one his colleagues after I re-checked the author names on the publications) but my perspective that their research was fake remains unchanged. You see, the fellow you are complaining about was just one of several people who cofirmed that they had been publishing an irreproducible stuff all along and that they were under a great pressure to do so because their investors were getting antsy. There is no myth about that. Even the professor confirmed to me eye-to-eye that the stuff I tried to reproduce was bad. Then he blatantly plagiarized my unpublished work.

    Comment by milkshake — July 8, 2007 @ 10:53 pm


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