2005 PNAS Arabidopsis cold sensitivity gene paper retracted

There’s a retraction this week from the Proceedings of the National Academy of Sciences of a paper that first appeared online on July 1, 2005 (and which is still available, but notes under “this article” that “a retraction has been published”). The paper reports on a study that allegedly found a gene that made Arabidopsis plants — a favorite model of molecular biologists — “extremely sensitive to freezing temperatures, completely unable to acclimate to the cold,” and very sensitive to salt.

In other words, the Arabidopsis version of our relatives in Florida.

From the retraction:

The authors wish to note the following: “The locus AT1g35515 that was claimed to be responsible for the cold sensitive phenotype of the HOS10 mutant was misidentified. The likely cause of the error was an inaccurate tail PCR product coupled with the ability of HOS10 mutants to spontaneously revert to wild type, appearing as complemented phenotypes. The SALK alleles of AT1g35515 in ecotype Columbia could not be confirmed by the more reliable necrosis assay. Therefore, the locus responsible for the HOS10 phenotypes reported in ecotype C24 remains unknown. The other data reported were confirmed with the exception of altered expression of AT1g35515, which appears reduced but not to the extent shown in Zhu et al. The authors regrettably retract the article.”

Didn’t follow all that?

Well, we didn’t either. Luckily, Retraction Watch has a molecular biology guru in its back pocket: Jeff Perkel, a mol bio PhD and former colleague of one of ours — Ivan’s — at The Scientist.

Perkel explained that what the researchers were doing was fairly standard. They looked for a plant that was sensitive to cold, figured out what they thought was the bit of DNA that made it that way, and cloned — in other words, made lots of copies of — that DNA fragment. The plan was to then stitch a normal copy of that fragment into the cold-sensitive plant, which should have made the plant normal again.

But a funny thing happened on the way to that flora. (Sorry, making sure you’re following along.) The bit of DNA the researchers thought they were copying turned out not to be the right one. The retraction doesn’t specify what went wrong there.

Then another strange thing happened. It turned out that the plants the researchers were using could become normal all by themselves, without any genetic intervention. So they were a lousy test of whether the DNA fragment — even had it been copied properly — was the right one.

In other words, says Jeff, it’s as if scientists had tried gene therapy on a sick patient, only to find out that the patient’s identical twin, also sick, got better by himself. If the gene-treated twin got better, they’d have no way to know whether it was because of the treatment or because he just got better on his own like his twin.

According to the original study, the work was important because it turns out that very little of the research scientists have done on what happens to plants when they freeze has helped breed plants that can withstand cold weather:

Much research has focused on the particular details of cellular function that fails under freezing conditions. This approach has not been very instructive in the actual mechanisms of tolerance. Guy (21) has pointed out that the large volume of reports on the when and where of freezing injury in plants has not led to any particular method or approach by which increased freezing tolerance can be achieved in plants.

Of course, now it turns out this paper is unlikely to lead to any such methods either. But the alleged gene find was noticed by other scientists: The study has been cited 57 times by other papers, according to the Thomson Reuters Web of Knowledge (disclosure: Reuters Health, where Ivan works, is obviously also part of Thomson Reuters). That puts it above average for molecular biology — in other words, other scientists have paid attention to this paper, and it has informed their work to some extent. What happens to those papers now, of course, remains to be seen.

We sent PNAS editor Randy Schekman an email for details on this retraction, and will update if we hear back.

Update, 3 p.m. Eastern, 8/5/10: Schekman responded to my emailed questions with his own email:

The corresponding author, Ray Bressan, contacted us when he discovered the error in the work.  A Board member handled the discussion and all the authors cooperated in the decision to retract the paper.  I have no way of knowing if this will have an effect on ongoing research.  Because the authors brought this to our attention and have been completely cooperative, we see no need to issue any sanctions.

Hat tip to PhysioProf, whose post on the DrugMonkey blog has a more, um, not entirely safe for work explanation of the retraction.

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