On second thought: PNAS retracts two papers after results fail replication

The Proceedings of the National Academy of Sciences (PNAS) ran two retractions this week.

One of those papers was “Properdin homeostasis requires turnover of the alternative complement pathway,” which first appeared online in October of last year. The researchers were looking at the interaction between complement — a sort of primitive immune system — and a protein called properdin.

From the notice:

The authors wish to note the following: “Our recently published PNAS paper is incorrect in that properdin is not reduced by approximately 90% in C3−/−, factor B−/−, or factor D−/− deficient mice. Properdin is also not consumed in mice depleted of C3 and factor B using cobra venom factor to activate the alternative pathway. We made an error in interpretation of a pull-down assay followed by Western blotting to measure mouse properdin that used a polyclonal antibody raised to human properdin. In retrospect, the problem arose because of reduced reactivity of the cross-reacting antibody for mouse properdin and the unrecognized activation at 4° C of the alternate pathway by Sepharose. The latter provided a substrate, C3b, to which properdin could bind in the pull-down assay. During further experiments using a newly available polyclonal antibody prepared to mouse properdin, we became aware of these issues with the former assay.

“The undersigned authors want to notify colleagues interested in this line of investigation so that they will not spend time and funds on following up on these observations. We regret any confusion we have caused in the immunology community and hereby retract this work.”

Another way to put it: Events conspired against us. The result we thought we had wasn’t for the reasons  we reported.

Only two of the paper’s three authors signed the retraction, although PNAS tells us that all three agreed to the language in the notice. The paper’s corresponding author, John P. Atkinson, told us:

Tommy Xu was and still is an undergraduate student. He worked on the project early on. He was not meaningfully involved in the project thereafter and was not responsible for the error. He is aware though of the events that have taken place.

We wrote a longer piece explaining in detail what led to our misinterpretation of the data along with Western blots to show the normal levels of properdin in the various mouse strains that we had thought were low but PNAS elected to show only the abbreviated version.

We asked if Atkinson would share that longer version, and he said he’d check with his co-authors.

The other paper, “A prion of yeast metacaspase homolog (Mca1p) detected by a genetic screen,”  by Julie Nemecek, Toru Nakayashiki and Reed B. Wickner, was first published online in January 2009. It has been cited 34 times, according to Thomson Scientific’s Web of Knowledge. According to the notice:

The authors wish to note the following: “In our efforts to extend our published paper, we now find that we cannot reproduce certain results reported there. Specifically, all transformants of strain 4827 carrying p20MCA (lacking p1116) are Ade+, making selection of prion-containing cells impossible. Also, strains denoted mca1Δ have a normal MCA1 gene. Other efforts by R.B.W. and T.N. to demonstrate a prion of Mca1p have also been unsuccessful. We therefore retract the paper.”

The researchers were searching for new types of prions — the nasty proteins that cause mad cow disease — and it looks as though the strains of yeast they were looking in didn’t have the characteristics they thought they did. That means they may not have found prions after all. We tried to get more details from Wickner, the corresponding author, but haven’t heard back yet.

Wickner, we should note, seems quite scrupulous about correcting the scientific record, and has a healthy sense of humor about it. In a 2000 letter to Nature called “Give credit where it’s due (not to me, this time),” he writes:

Sir — In his interesting review of Stan Prusiner’s Prion Biology and Diseases, Colin Masters inadvertently gave me credit for showing “that accessory chaperones…may facilitate the conversion of a normal host-cell protein into a pathogen”. Although I can take credit for discovering that [URE3] and [PSI] are prions of yeast, the credit for discovering the role of chaperones in this phenomenon goes to Yury Chernoff and colleagues.

Any chagrin I may feel at being inappropriately credited is measurably mitigated by the knowledge that there will inevitably be occasions when I will be ‘unintentionally’ ignored.

Hat tip: Commenter Philip

3 thoughts on “On second thought: PNAS retracts two papers after results fail replication”

  1. Just want to say that I like these retractions, because they clearly indicate what was wrong, and in the case of paper 1 even why; which, in itself, could be an interesting observation (if not already known).

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