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MIT Probe Finds Former Postdoc Falsified Images

Misconduct: Cell paper about imaging nerve connections retracted; new study addresses issues

by Carmen Drahl
February 20, 2013 | A version of this story appeared in Volume 91, Issue 8

Credit: PLoS ONE
The Ting lab’s new technique displays a fluorescent signal (arrowheads) when neurexin and neuroligin interact.
In rat neurons, Alice Ting’s new technique, ID-PRIME, displays a fluorescent signal (arrowheads) when the proteins neurexin and neuroligin interact
Credit: PLoS ONE
The Ting lab’s new technique displays a fluorescent signal (arrowheads) when neurexin and neuroligin interact.

A former MIT chemistry postdoc fabricated figures in a 2010 publication, a university investigation has concluded. The report described a way to image an important interaction on the surfaces of living nerve cells. The journal Cell retracted it on Feb. 14 at the request of principal investigator Alice Y. Ting (DOI: 10.1016/j.cell.2010.09.025). But the detection method actually works: In a simultaneous publication appearing in PLoS ONE, Ting’s team redesigns the technique, backs it up with higher quality data, and introduces a next-generation method that seems to function even better (DOI:10.1371/journal.pone.0052823).

The retracted method, called BLINC (biotin labeling of intercellular contacts), was designed to detect interactions between the proteins neurexin and neuroligin. The pair is among several brain proteins involved in synapse formation. Mutations to them have been implicated in autism.

According to the retraction notice, Ting learned that her lab couldn’t reproduce the work, prompting MIT’s investigation. The probe concluded that first author Amar Thyagarajan, Ting’s former postdoc, faked data and “was solely responsible for the scientific misconduct.” Thyagarajan declined to sign the retraction notice.

BLINC was supposed to create a fluorescent signal only when neurexin and neuroligin interact. A mock-up of BLINC in kidney cells worked, Ting’s team found, but the method failed in neurons. It turned out neurons weren’t getting enough of the engineered enzyme Ting’s lab made to generate fluorescence. After fixing that, BLINC worked in neurons. But Ting’s team went a step further—they developed a new method using a different enzyme that provides a stronger fluorescence signal. Her lab has patented the technique, called ID-PRIME (interaction-dependent probe incorporation mediated by enzymes).

The new report “does an excellent job of clarifying why data in the initial paper were problematic,” says Craig C. Garner, who studies synapses at Stanford University. He thinks ID-PRIME “should find legs in the synapse community,” once the levels of engineered enzyme on neuron surfaces can be tightly controlled.

Ting tells C&EN she isn’t at liberty to discuss the retractions or the new paper. “The science in the papers kind of speaks for itself,” she says.

C&EN received a statement from Thyagarajan that first appeared on the blog Retraction Watch, which broke the story. Thyagarajan has resigned his position as a technology specialist at Boston patent law firm Clark & Elbing.

“I was not contacted by Cell about their decision to retract the paper. I want to be clear that the retraction was done over my objection,” Thyagarajan said. “I stand by the data that was published and the methodology that I developed. I and others have reproduced this method over four years. The findings against me were the result of a deeply flawed and sloppy investigation that ignored evidence that someone had tampered with and deleted my data, after the publication of the paper, and made it look as if I had falsified data.”

Thyagarajan said that the matter is now being investigated by the federal Office of Research Integrity (ORI), which investigates scientific misconduct allegations when the research is supported by federal funds. “I expect to have a full and fair opportunity to be heard before impartial fact-finders and am confident that my innocence will be established,” he added.

As required by federal privacy acts, ORI can neither confirm nor deny its involvement, says ORI Deputy Director John E. Dahlberg.


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