Retraction

The scientific community has its own version of Hollywood. But, rather than making films, scientists produce research papers and thus communicate important discoveries. And, as with Hollywood stardom, scientific fame often involves intense scrutiny: the more exciting and impactful a scientific discovery, the more interest and examination it will garner from the scientific community.
Six months ago, two scientific articles and the researchers behind them catapulted to stardom. Published in the prestigious journal Nature, these articles reported a simple method for creating stem cells. Because stem cells are pluripotent, meaning they can give rise to many different types of cells (skin cells, heart cells, blood cells, etc.), this achievement represented a scientific Holy Grail, and researchers around the world sat up and took notice.

Six months ago, two scientific articles and the researchers behind them catapulted to stardom with reports of a simple method for creating stem cells. However, it quickly became clear that these articles were too good to be true. Now, after months of debate, lead author Haruko Obokata (left) from the RIKEN Center for Developmental Biology in Kobe, Japan, senior authors Teruhiko Wakayama (center) from RIKEN and Charles A. Vacanti (right) from Harvard Medical School, and all the other authors have unanimously agreed to retract both articles.

However, it quickly became clear that these articles were too good to be true. Now, after months of debate, lead author Haruko Obokata from the RIKEN Center for Developmental Biology in Kobe, Japan, senior authors Teruhiko Wakayama from RIKEN and Charles A. Vacanti from Harvard Medical School, and all the other authors have unanimously agreed to retract both articles. Just as cinemaphiles follow a starlet’s rise to and fall from fame, the scientific community closely monitored the controversial articles’ six-month road toward retraction. Finally, on July 3, 2014 Nature published a note by the researchers formally retracting their studies.
The first problems with the articles emerged just days after their January publication. Many researchers pointed out that certain figures in the articles had been manipulated in a way that weakened the strength of the argument the figures were meant to support. The RIKEN Center, the home institute of several of the authors, took these allegations very seriously. RIKEN launched an internal investigation, concluding in April that these manipulations constituted scientific misconduct. In response, the authors acknowledged the manipulations, but they claimed that they were due to inexperience rather than to intent to deceive.
However, the scientific community pointed out an even graver problem: many laboratories tried and failed to reproduce the crucial procedure reported in the articles, called stimulus-triggered acquisition of pluripotency, or STAP. Pluripotent stem cells are notoriously difficult to create—complex genetic reprogramming is always required. However, Obokata and her colleagues reported that they had created stem cells from young mouse white blood cells using the STAP method, which involved simply stressing the cells by bathing them in acid. Stem cell researchers around the world tried to reproduce the "simple" acid bath method, but none succeeded in doing so, raising questions regarding the efficacy of the procedure and the accuracy of the authors' reporting.

In response to reports of failures to reproduce their results, Obokata and her colleagues quickly published detailed instructions for the STAP procedure, including 28 important "tips" for success. The authors acknowledged that, while the procedure seems simple, it "requires special care in cell handling and culture conditions," suggesting the acid bath procedure is not as easy as it originally seemed to be. Although these tips were published in early March, they did not enable any scientist to subsequently reproduce the STAP phenomenon.

The Retraction Trajectory

While some of the authors struggled to keep up with accusations, one of the senior authors, Teruhiko Wakayama, called for withdrawing the articles from publication, or "retracting" them." Retracting a scientific article indicates doubts about the integrity of the research and raises questions about the validity of the scientific findings. While scientific papers are rarely retracted, retraction is a standard course of action when published research is found to be substantially flawed. This may be due to deliberate scientific misconduct, such as falsifying data or fabricating figures, but may also be due to innocent mistakes, such as mislabeled samples. Some scientists have voluntarily withdrawn papers once they realize they've made mistakes.

Regarding his decision, Wakayama said that "to investigate the study's validity, we must first retract it, collect the right data and photos, and try to prove again that the study was right." Since Wakayama is a world-renowned scientist known for cloning the first mice, his withdrawal of support from the articles set in motion a chain of events leading to retraction. While the ultimate decision to retract rested with Nature, the journal that published the articles, it is standard procedure for all authors to agree to retract before a journal does so.

Harvard University

Vacanti argued that retraction would be tantamount to admitting the STAP procedure does not work. However, on May 30, Vacanti unexpectedly agreed to retract the papers.

As the controversy surrounding the papers increased, only two authors refused to retract them: one of the senior authors, Harvard's Vacanti, and the lead author on both papers, Obokata. Retraction, they argued, would be tantamount to admitting the STAP procedure does not work. Until recently, both these researchers stood behind the papers and their findings, but on May 30, Vacanti unexpectedly agreed to retract the papers, leaving Obokata as the only holdout.

The Last STAPle in the Coffin

The final blow to the STAP articles came when Wakayama submitted some of the STAP cells for genetic analysis. In their papers, the authors claimed to have turned young mouse white blood cells into pluripotent stem cells. They also claimed that the STAP procedure could produce stem cells from multiple strains of mice commonly used in scientific research. These mouse strains are all genetically distinct, so, by testing the STAP stem cells, scientists would be able to determine the mouse strains from which they originated. Shockingly, genetic analysis revealed that the stem cells did not come from the mouse strains they were said to have come from, leading some scientists to suggest that the cells might have been contaminated. Perhaps the original cells were contaminated with cells that were already stem cells, misleading the researchers into thinking they had "created" pluripotent stem cells via the STAP technique when such cells had in fact been present all along.

The final blow to the STAP articles came when Wakayama submitted some of the STAP cells for genetic analysis. The analysis revealed that the stem cells did not come from the mouse strains they were said to have come from, leading some scientists to suggest that the cells might have been contaminated.

Finally, in early June, falling in line with the rest of her colleagues, Obokata agreed to retract both papers. That decision led to the publication of a formal statement of retraction in Nature July 3. The statement acknowledged that “critical errors” had been found in the Article and Letter that appeared in Nature, and that the RIKEN review “has characterized some of the errors as misconduct.” It concluded with the following paragraph: “We apologize for the mistakes included in the Article and Letter. These multiple errors impair the credibility of the study as a whole and we are unable to say without doubt whether the STAP-SC phenomenon is real. Ongoing studies are investigating this phenomenon afresh, but given the extensive nature of the errors currently found, we consider it appropriate to retract both papers.”

A Peer Review Triumph or a Failure?

All scientific papers are rigorously examined prior to publication. Because qualified scientists conduct these examinations, this process is called "peer review." However, once a paper is published, anyone in the scientific community can read and analyze it, and, most important, try to reproduce its results.
Some critics have expressed shock that the STAP papers even made it through the peer-review process and ended up getting published. Yet the excitement surrounding the papers quickly led to a detailed examination and questioning of their results by the broader scientific community, amounting to a much larger and more comprehensive peer-review process. So, if the STAP phenomenon turns out to be an illusion, the scientific community as a whole will have been shown, once again, to be an effective guardian of the integrity of its members.

Discussion Questions

How could the peer review process be improved? Do you think manipulated figures published in less prominent papers are more or less likely to be caught? The STAP papers were widely discussed by the mass media. How do you think the general public will view the misconduct allegations and the eventual decision to retract?