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Cloner Finds New “Acid Bath” Paper Errors; Scientist OKs Retraction

Thu, 05/29/2014 - 2:14pm
Cynthia Fox

Riken's Haruko Obokata has finally agreed to retract one of Nature's highly controversial "acid bath stem cell" papers.“I do not know if there is any real data in these two papers,” said Yamanashi University cloning pioneer Teruhiko Wakayama to Bioscience Technology by email this Monday.  “I do not believe anymore in STAP cells.”

Mere days later, Riken Institute scientist Haruko Obokata told the Japanese press she would retract the second of two Nature papers claiming adult cells dedifferentiate into stem cells via the stress of coffee-mild acid. The controversial stem cells are called STAP cells, as Wakayama called them: “Stimulus Triggered Acquired Pluripotency" cells.

That second paper was written under the tutelage of Wakayama, its senior author. It describes experiments done to prove the stem cells Obokata said she created were totipotent (able to form all cells including placenta). Wakayama was the first co-author to come forward publicly, mere weeks after the papers’ publication in January, to urge withdrawal due to errors found in the first paper.

Wakayama worked with cells that Obokata handed him, he told Bioscience. He had only personally been able to make STAP cells once—and then, with her physically present.

For many weeks after his initial calls for withdrawal, however, Wakayama continued to support the idea the experiments should be started over again, offering his hope the stem cells might be made, just using a better protocol, sans errors.

This Monday, however, he noted for the first time, as shown above, that he no longer believes in STAP stem cells, at all.

The Trigger

The trigger, he told Bioscience, was his discovery—which he reported to Riken a few weeks ago--that two key photos in the second paper were wrong. Obokata, lead author on both papers, had in April been found by Riken guilty of misconduct on the first paper: the falsification of a gel electrophoresis image proving her starting cells were mature cells, and the fabrication of images proving resulting STAP stem cells could form the three major tissue types of the body.

But Riken had not yet announced serious problems with the second paper.

Last week, however, there was a flurry of activity in the Japanese press, as papers reported that two photos—supposed to show placenta made from STAP cells, next to placenta made from embryonic stem (ES) cells—were actually photos of the same mouse placenta.

Wakayama on Monday told Bioscience that he was the one to report the problem to Riken, slightly differently than what was reported in the English translation of the Japanese papers. That is, both photos were of placenta made from STAP cells--if from different mice, he said.

“I reported those mistakes to Riken a few weeks ago. In the Nature paper, one picture showed STAP chimera, another showed ES cell chimera,” he said. Chimera are animals born of cells from different species. “However, those two pictures are both derived from STAP chimera, just different individuals. I do not know why Dr. Obokata used STAP chimera picture as ES cell chimera, because there are many pictures about ES cell chimera in the same PC.”

Wakayama said further: “Anyway, in Japan, now, several newspapers have reported that not only chimera pictures, but also some other figures are mistakes.”

Wakayama is responsible for many historic cloning firsts, including the cloning of the first mice. He was one of numerous co-authors on the two STAP papers. The Japanese press reports co-author Yoshiki Sasai of Riken will join Wakayama and Obokata in calling for the second paper’s retraction.

This winter, press worldwide lavished attention on the two Nature papers. If adult cells could easily turn into stem cells, regenerative medicine could have been transformed. But almost immediately, Japanese and American scientist bloggers, including Juuichi Jigen and Paul Knoepfler, began to point out serious errors. They also noted the papers' irreproducibility, recently confirmed by the Chinese University of Hong Kong's Kenneth Lee in an F1000 Research paper generating over 5,000 hits so far.

Harvard University’s Charles Vacanti, senior author on the first Nature paper, did not immediately respond to a request for comment last night.

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