Somatic Biology), Yoshiki Sasai (co-author; CDB Deputy Director),

Somatic cells make up most of the part in mammalian body such as internal organ, connective tissue, blood and bones through cellular differentiation process. However, Obokata and her colleagues discovered an unexpected reprogramming phenomenon, known as stimulus-triggered acquisition of pluripotency (STAP). Genetic manipulation or transfer of nucleus were unnecessary in this reprogramming procedure, in which mouse somatic cells such splenic CD45+ lymphocytes regained pluripotency after exposure to low pH medium.  Besides that, injected progeny of embryonic stem (ES) cells seldom appeared in the placental lineages but can be found extensively in the embryonic part of chimaera. Surprisingly, in blastocyst injection assay, STAP cells not only contributed to embryo but presented around 60% of placental tissues and fetal membrane in the chimaera whereas those tissues were not appeared in the ES cells. Hence, STAP cells included pluripotent cells (Oct41Cdx22) and trophoblast-stem-like cells (Oct42Cdx21). In addition, by treatment with adrenocorticotropic hormone (ACTH) and leukaemia inhibitory factor (LIF), mouse STAP stem cell unable to differentiate into placental lineages and only expressed little trophoblast marker genes. When exposed to Fgf4 medium, STAP cells converted into trophoblast-stem-like cells that was unusual with ES cells or STAP stem cells. These cells known as Fgf4-induced stem cells with enhanced trophoblastic characteristic. Fgf4-induced stem cells contributed to embryonic and placental tissues in vivo as opposed to blastocyst-derived trophoblast stem cells, meanwhile those cells can transform into ES-like cells while cultured in LIF+FBS-containing medium. From the analysis of the molecular features (in vitro cell conversion and chimaera formation), it can be concluded that conversion of STAP cells were distinctive and went beyond pluripotent state that involved differentiation of trophoblast.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

A)      In 500 words maximum, describe the ‘fallout’ from this paper’s publication over the subsequent months and years. What happened, when, and to whom?

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In January 2014, Obokata published a pair of articles in Nature by revolutionizing a new method to reprogram stem cells by bathing differentiated cells in acidic condition to make them pluripotent. Soon, arguments and doubts were raised regarding her publication ethics and validity due to her simplicity of work.

 

From February till end of March, the Riken research institution launched a full investigation into this case. The Investigative Committee handled this issue under Regulations on the Prevention of Research Misconduct. They examined all the relevant materials and interviewed four individuals concerned, Haruko Obokata (main author; Head of the Laboratory for Cellular Reprogramming, Riken Center for Development Biology), Yoshiki Sasai (co-author; CDB Deputy Director), Teruhiko Wakayama (co-author; professor and Riken’s senior scientist) and Hitoshi Niwa (co-author; Project Leader of the Laboratory for Pluripotent Stem Cell Studies, Riken CDB).

 

Several errors were found in the papers. For instance, in this particular paper reported the similarity of rightmost panel in Figure 1b and the lower panel in 2g as both indicated the presence of fluorescence in mice placenta. Riken had cited Obokata for research misconduct on two out of six points. They concluded that Obokata was an immature and lack of sense of ethics as a researcher. Her unbelievable carelessness behavior and sloppy data management, made the team difficult to trace her data and formed a barrier for changing information between scientists.

 

Soon, in June 2014, two published papers were retracted from Nature due to allegations of data fabrication and falsification. Yet, Nature confirmed again the retraction of papers on 2 July 2014. From this incident, public criticised on Dr. Wakayama and Dr. Sasai for poorly supervision of Obokata. On 5 August 2014, Dr. Sasai was committed suicide after suffering from depression. On the other hand, Obokata was given the last chance to work in Riken under full supervision from third party in order to prove her so-called STAP cells do exists. However, she failed to replicate her experiments and decided to resign from Riken on December 2014. There were also conflict between Wakayama and Obokata regarding the origin of the cells. According Japan Times, she also got into the case of stolen embryonic stem cell at CDB. 

 

The Riken centre restructured, implemented new systems and reformed new management teams to prevent further misconduct. The consequences of this incidents shocked the whole Japanese scientists and prompted Japan to execute anti-fraud regulation. Besides that, Obokata’s doctoral thesis also being forfeited by Waseda University in November 2015. She will never do research again since no one believes her. Nevertheless, she herself still convinced of the existence of STAP cell. In January 2016, she published a book entitled ‘Anohi’ which describing STAP cells event. Moreover, ‘STAP HOPE PAGE’ was established in March 2016 by disclosing all the methods in order to assist future researchers in investigating STAP phenomenon.  

 

 

 

 

 

 

 

 

 

 

 

B)      In 500 words maximum, write a summary of your views on the ethics and the personal motivation/psychology that drove Obokata to this level of misconduct. Additionally, what is your opinion on the institutional/scientific journal/media handling of this case?

 

In my opinion, research ethics is very important by encouraging healthy information exchange within scientific community, yet bringing contribution to the whole population in future. Firstly, Obokata committed this ‘crimes’ by virtue of personal ethics failings. She is considered a scoundrel and immature researcher. It is hard to believe she did not aware of the danger despite of her carelessness and made those published data lost its credibility. Her misconduct behaviour was totally unacceptable ended up her to join the world ranks of biomedical fraudsters.

Besides that, Obokata wanted to success in her career. At around 30 years old, she was appointed as the head of the laboratory at the Riken Centre for Development Biology (CDB), Japan. Furthermore, she managed to publish two simultaneous articles in Nature, which is one of the world’s prestigious scientific journals. If she manages to publish more papers, she can gain incentives by selling data and easily promoted to a higher position. She can also build her personal reputation and legacy throughout the general public.

Moreover, she can easily attract more funding from third parties in order to support her works. Yet, plagiarism, falsification and fabrication of data are the cutting corners methods to help her to get the results faster or produce convincing results. Aside from being a truth-seeker, scientist normally prefer to become the first person to make a discovery. Same goes to Obokata, she claimed the existence of stimulus-triggered acquisition of pluripotency (STAP) cells but turned out no one can make this simple experiment work. Pressure from organisation or personal stress may also become of the reasons to force Obokata to perform this level of misconduct. Probably, she has been forced to establish some achievements within certain limited period of time.

From my point of view, it was fair that Riken institute handled this misconduct case by investigating all the procedures, materials and personnel involved. This action not only to protect the company, giving chance to Obokata and also able to prove the truth of the research. Although public criticise on the failure of the system in checking Obokata’s work, Riken institute was reconstructed after Obokata resigned. Indeed, they offered Obokata to honour Sasai’s dying wish to reproduce STAP cells. This action revealed that Riken institute focused in finding the truth and gave the last respect to their employees. Eventually, they also reported Obokata found guilty of misconduct after she failed to replicate the experiments.

Aside from that, scientific journal, Nature decided to retract Obokata’s articles without prejudice to avoid misleading of the information. Nonetheless, social media was merciless by spreading news throughout the world putting heavy pressure on Obokato and her co-author, Yoshiki Sasai. Perhaps social pressure and personal issues caused both of them suffered from depression. Unfortunately, Sasai committed suicide in early August. Indeed, more time should be given to them in handling the case. To conclude, this incident warned the public how severely the punishment of being dishonest.