Stem Cell Shock Articles Retracted

Two controversial stem cell articles, after twisting in the wind for months, have finally been retracted. The articles, prepared by scientists based at RIKEN, asserted that adult cells could be transformed into pluripotent stem cells by means of physical stresses, such as acid shock, instead of genetic manipulation. While the articles immediately gained blockbuster status, they also attracted intense scrutiny. Then, soon enough, skeptical readers pointed to irregularities in the article’s figures. In addition, plagiarized passages came to light. Finally, and perhaps most seriously, the article’s findings seemed to defy replication.

Although all the co-authors of both papers have agreed to the dual retraction, they still hope that their work will be confirmed. For example, one of the researchers, Charles A. Vacanti, M.D., head of the Department of Anesthesia at the Brigham and Women’s Hospital, said in a statement that he was “encouraged by recent news, which suggests that Minister Hakubun Shimomura and RIKEN President Ryoji Noyori will allow sufficient time to replicate the core STAP [stimulus-triggered acquisition of pluripotency] cell concept.” Dr. Vacanti added that he trusted that the STAP concept would be verified by RIKEN as well as independently by others.

A statement was also issued by the journal Nature, which published the two articles on January 30. The statement directs readers to a tightly written retraction prepared by the authors of the original stem cell articles. After citing the errors that were highlighted by a RIKEN investigation, and acknowledging that RIKEN determined that some of the errors amounted to misconduct, the retraction offered an apology and concluded as follows: “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.”

For its part, Nature has taken the retractions as an opportunity to review its practices: “Although editors and referees could not have detected the fatal faults in this work, the episode has further highlighted flaws in Nature’s procedures and in the procedures of institutions that publish with us. We—research funders, research practitioners, institutions, and journals—need to put quality assurance and laboratory professionalism ever higher on our agendas, to ensure that the money entrusted by governments is not squandered, and that citizens’ trust in science is not betrayed.”

Nature in its statement noted that it did not believe that the errors in the STAP work that initially surfaced fundamentally undermined the articles’ conclusions. Also, Nature noted that replication of such work is not necessarily straightforward or quick. Nonetheless, Nature indicated that it was concerned by the results of the RIKIEN inquiry. For example RIKEN concluded that the STAP study’s leader, Haruko Obokata, Ph.D., was guilty of misconduct.

Nature also indicated that it had reviewed referee reports and its own editorial records: “Our policies have always discouraged inappropriate manipulation. However, our approach to policing it was never to do more than to check a small proportion of accepted papers. We are now reviewing our practices to increase such checking greatly, and we will announce our policies when the review is completed.”

The retracted papers will still be hosted on the Nature website; however, they have been watermarked to indicate their retracted status.


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About the Author

Michael KH Ling

My research group is interested in deciphering the genetic components that regulate the molecular networks underlying the development of the mammalian brain. Our current research focus includes: (1) characterisation of the role of long non-coding RNAs during brain development, (2) characterisation of novel microRNAs involved in embryogenesis (3) transcriptomic analysis of Down syndrome mouse brain, and (4) molecular screening of nucleic acid aberrations in selected neurological disorders. Distorted communications between proteins have been proposed as the cause of various mental health conditions including mental disability of various spectrum especially in patients diagnosed with autism, schizophrenia, Down syndrome or Alzheimer’s disease. Unfortunately, our current understanding on the communicational networks between proteins during normal brain development remains inadequate. Since the mouse and human share about 85% of imprinted information and undergo almost identical brain developmental stages, we, therefore, in collaboration with Professor Hamish Scott (University of Adelaide), studied the mouse brain obtained from various developmental stages that resemble the human brain at the first trimester, third trimester, after birth as well as at senescence. In the analysis we compared and noted all the changes of the amount as well as type of mRNAs found in each stages of brain development and use them to infer the underlying communicational networks at the protein level. From our observations, we outline a benchmark for networks comparison between the normal and abnormal brain development conditions. We identified 70 mRNAs/proteins and groups of novel RNAs that do not bear any information for the production of proteins. These mRNAs or novel RNAs were specifically produced in specific regions of the brain at specific developmental stages. Our group are interested in deciphering the role of these differentially regulated transcripts in brain development. Figure 1: An example of how molecules are connected intracellularly (A) and related to various neurological disorders (B). Sourced from Ling et al, Genome Biol, 2009; 10(10):R104. Figure 2: The expression profile of a novel non-protein coding transcript known as Nrgn antisense transcript in different adult mouse brain cells. Sourced from Ling et al, Cereb Cortex, 2010: doi:10.1093/cercor/bhq141