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At a press conference held by the Japan Institute of Science and Chemistry on January 28, 2014, a research team led by 30-year-old Hiroko Obao, head of the research team, announced the success of a new kind of "omnipotent cell" STAP cell. Its significance goes beyond the discovery of iPs cells by Nobel laureate Professor Shinya Yamanaka.

Unlike technologies such as iPS cells, the highlight of this innovative technology is that cells can be changed simply by changing the external environment and giving cell stimulation, Obokata claimed. She believes that the technology should be able to contribute to areas such as regenerative medicine and immune research.

At the same time, Obofang published two papers on STAP cells in the British journal Nature. The co-authors include the famous developmental biologist Yoshiki Sakai, cloning expert Yoshihiko Ruoyama, and Harvard professor Charles Vacanti.

Obofang, Sakai and Ruoshan at the ▲ via:premiers-igaza.biz Riken press conference

The new discovery brings unlimited new possibilities to the future of regenerative medicine, and Hiroko Obokata has become a hot star in Japanese science overnight.

Young female scientists, wearing cooking clothes to do experiments-Xiao Baofang's body is covered with media favorite labels, causing a "Xiaobao Fang craze."

However, just two weeks after the launch, various comments about the STAP cell paper appeared on the Internet, with several images accused of scientific misconduct and about 20 lines of plagiarism.

The magazine Nature and Riken have launched investigations one after another.

On April 1, 2014, the investigation committee of the Japanese Institute of Science and Chemistry released the results of the investigation that Akiko Obokata had tampered with and fabricated improper behavior in her STAP cell paper.

After that, the Japanese Institute of Science and Chemistry officially announced that the so-called "STAP" cells could not be replicated, putting an end to the controversial research.

Koibao Fang Qingzi fell from the altar of a scientific research star overnight, and Yoshii Sasai, a leading stem cell expert who has been supporting STAP and is thought to be expected to win a Nobel Prize, committed suicide under pressure.

▲ questioned the image of the paper

The STAP cell incident is one of the three major scientific research scandals in the 20th century, alongside the Shane incident and the Hwang Woo-suk incident. The co-author of the STAP cell paper includes not only Hiroko Obokata and a group of world-class scientists in Japan, but also American professors at Harvard University.

The Japanese Institute of Science and Chemistry (referred to as "Riken"), which belongs to the Ministry of Education, Culture, Science and Technology, founded in 1917, is the only comprehensive research institution of natural science in Japan. It brings together top scientists in physics, chemistry, mathematics, engineering, biology, medicine and other fields.

Fake scientists (Japan) by Taozi Sutian, translated by Wang Jiamin

Reporter Sutian Taozi followed the interview all the way, exclusively interviewed a large number of relevant people in the academic circles, including the late Professor Sakai, investigated and reported the whole process of the STAP cell paper being proved to fabricate and tamper with the content, discussed the deep causes of academic misconduct, and wrote the scientific documentary work "the fake Scientist." The fake scientist won the Zhuangyi non-fictional Literature Award and the Science journalist Award.

STAP cell events can never be blamed on a particular person. Problems have arisen at all stages of the experiment, the discussion in the laboratory, the publication of the results, the handling of suspected fraud, and even the education of the first author in graduate school.

I think there are some structural problems lurking, which are eroding the frontline of Japanese scientific research, Mr. Suda wrote in his book.

What is the fate of Xiao Bao Fang Qingzi after it has been proved that scientific research has been falsified?

Xiao Bao Fang Qingzi failed to reproduce the experiment and failed to complete the revision of the questionable doctoral thesis on schedule, and his doctorate was revoked in November 2015.

In January 2016, Xiao Baofang published the notebook "that Day" recording the "truth" of the incident, which quickly became a bestseller.

In March 2018, she published her second book, the Diary of Kobao Fang Qingzi, which records how she "struggled alone" after the STAP incident.

Let's take a look at what happened after the STAP event.

▲ in December 2014, a team from the Japan Institute of Science and Chemistry announced the results of the repeated experiment. Photo Source: nature.com

The Legacy of the STAP event in the final Chapter

By Taozi Sutian, translated by Wang Jiamin

The copyright of this article belongs to Shanghai Translation Publishing House exclusively and may not be reproduced or edited without authorization.

With the conclusion of the second investigation committee and the disciplinary action against the relevant personnel, the STAP cell incident, which was a major scandal, came to an end temporarily. Since then, however, the scandal has continued for more than a year.

The biggest topic is Xiao Baofang's handbook "that Day" (published by the talk Society), which was published in January 2016 and became a bestseller. When the doctorate was revoked in November 2015, Obokata's promise to publish the revised doctoral thesis and related data online remained unfulfilled. I was surprised at first that the notebook was published before fulfilling the promise. But it was the notebook of the person involved in the study that had not been publicly discussed since the press conference in April 2014, so I hastened to take a look at the sample booklet the publisher distributed to the media the day before it went on sale.

▲ 's notebook "that Day" is sold in the bookstore.

At the beginning of her notes, while apologizing for causing a series of sensations, she also described her writing motivation:

"I think it is a more despicable escape to keep quiet about this incident that has caused an uproar in society, waiting for the world to forget, and I have decided to tell the whole truth in this book. I will not hesitate to expose my weakness and immaturity to the world."

What kind of "truth" is it? I looked forward to reading the facts that were not found in the interviews and two investigations by the commission of inquiry, but gradually I found that this expectation was only disappointment. This is because there is a lot of disagreement in the accounts related to the misconduct identified in STAP papers and doctoral dissertations. on the other hand, it is striking that Obofang did not write much "objective facts" against him, but also misunderstood the readers and even completely concealed some situations.

For example, with regard to the four teratoma images in the STAP paper identified by the first investigation committee as fake, Obokata wrote:

"at the beginning, the research papers I wrote when I was a student were all about changes in cells caused by a variety of stress treatments. In the process of rewriting the paper, I shifted my focus to the changes in cells caused by acid stress treatment, thus limiting the types of stress accordingly. In the process, I forgot to change the picture of the teratoma, which is the reason for the mistake. I didn't confirm it carefully, which led to such an error. "

However, as described in Chapter 5, in the first submission to Nature that was not adopted in April 2012, a total of nine pictures, including these four pictures, were used that are very similar to those in the doctoral thesis, and when they were re-submitted to the magazine in March 2013, five of them were replaced by other pictures. It is true that it is not "forgot to replace", but "replaced part". As for why the four problematic pictures were left at that time, there was no explanation in the handwriting.

As for the first identification of two cases of misconduct, she wrote: "I think this is the conclusion drawn under the attack of society, which makes me feel very sad." It is tiresome to have a light understanding of misconduct.

What is surprising is the description of the verification experiment:

The expression of pluripotent gene and Oct4 protein were observed with a certain reproducibility.

There is no doubt that the unknown phenomenon I found is correct, and the reproducibility of the 'STAP phenomenon' in the part of the experiment I am responsible for in the Ruoshan laboratory has been confirmed.

Such description strokes are like partial success in reproduction. However, these contents are not only contrary to the Liyan report described in detail in the previous chapter, but also do not provide specific data to prove "certain reproducibility". There is also no mention of the failure of reproduction experiments by seven research groups around the world.

As the notebook enters the second half, there are more and more descriptions of the deterioration of their physical and mental state due to stress. At the second inquiry committee hearing, "it was difficult for me to support my body" (the first description), and the hearing "was conducted when it was difficult to maintain even a normal conversation" (the second description). Deliberately stressed that his body was in the worst condition. Not to mention, the notes repeatedly stressed that they had been "forced to plead guilty".

For the two pictures newly identified as fraud, the notes give little specific explanation, replaced by explanations such as "charts are made to present reproducible experimental results". However, as described in the previous chapter, according to the committee's report on the two images, the results shown in the paper have never appeared once, and it is even doubtful whether the experiments that support the cell proliferation curve exist. Including these two items, the notebook does not provide any raw data for the chart category of the paper, nor does it mention the reasons for doing so.

▲ via:www.nippon.com/

The "truth" that Obokata most wants to tell can be seen in the account of Ruoyama. In his notes, the chimera mouse collaborator initially came across as modest and kind, but that impression changed rapidly as the research progressed. There are many descriptions in the book from the perspective of Obofang. For example, he is addicted to STAP research, violates Obokata's "idea" and semi-forcibly tries to lead the research. After the doubt is discovered, he changes his previous attitude, keeps his distance from the co-authors of CDB, and unilaterally publishes information. During interviews and hearings of the investigation committee, he repeatedly makes remarks intended to protect himself.

Interestingly, with regard to the emergence of the results of Endo Analysis and Ruoshan Analysis in June 2014, Obokata even wrote:

"I think it was carefully orchestrated to end the story of'I mixed ES cells'."

But there are only a few explanations about Riyan's scientific verification of the fact that it was mixed with ES cells. The most important thing, the fact that ES cells are mixed, is still ambiguous in the notes. "many (genetically analyzed) samples were made in Ruoshan's laboratory," and so on, causing readers to turn their skeptical eyes to Ruoshan's accounts everywhere. In contrast, genetic analysis of FI stem cells suspected of being deliberately mixed with two types of cells after Ruoshan transferred to Yamanashi University made no mention at all.

How does Xiao Baofang face and express the facts? As far as the nature of handwriting is concerned, there is no way for the author to write the content from a subjective standpoint, but since it is advertised in the opening remarks to "tell the truth completely", then the objective and important facts cannot be ignored. Although I wanted to reconfirm the factual relationship and true intention to the guarantor, the publisher informed the publisher when distributing the sample booklet that they did not intend to arrange an interview or hold a press conference with the guarantor himself.

How does the small insurer deal with the facts that cannot be confirmed in the information such as the report of the investigation committee? There is a kind of analysis that can be analyzed.

In particular, the interview offensive of Takeko Suda, a reporter from the Daily News, even made people feel murderous. Threatening e-mails flew to me in the name of 'interview'. This description of Obokata is a test of my own interview and the relevant reports of the Daily News.

Apart from the press conference, I have never met Xiao Baofang on other occasions, nor have I ever gone to her unit or home for an interview without an appointment. My attempt at independent interviews is basically based on emails, which have been saved, and I think I can rule out my own subjective factors and prejudices to check them. Although some people think that it is pointless for the accused person to carry out the test, I would like to write some words for reference.

▲ via:legacy.theskepticsguide.org

Shortly after the suspicion was discovered, Hideo Miki hired lawyer Hideo Miki as his agent. As a result, I sent only one email directly to Obokata himself in March 2014, and then sent more than a dozen emails to Miki lawyer by late October 2015. The contents of the email include applying for an interview, sending questions, confirming unanswered matters, requesting an interview again, and so on. Questions related to scientific doubts about STAP papers or the trend of withdrawing papers are basically the same as those asked to other responsible authors such as Sakai and Ruoshan. In 2015, I also asked about Xiao Baofang's doctoral thesis and academic papers based on it. Lawyer Miki replied many times and refused to answer questions on the grounds of Kobofang's "mental injury" and the instructions of the attending doctor, but in the end, I didn't get a single substantive answer. In his reply in October 2015, lawyer Miki wrote that he had not yet received a commission to respond individually to the media, nor could he forward the question to Obokata.

The notes of Xiao Baofang did not deal with the specific questions I raised and the actual contents of the email.

". Even if you take some kind of coercive posture, you have to ask me to give some kind of answer. this is her interview method."

"No matter what kind of reply and answer I give, she doesn't want to report the truth fairly."

Although Xiao Baofang has made such an account, since she has never replied to me and the interview has never been realized, even if I want to include some opinions and opinions of Xiao Baofang in the report, it is impossible to do so. This is the truth.

I read many times the contents of the emails I contacted with Kobao at that time, and I had to feel that "it makes people feel murderous", "I think this method is violent,"threatening emails," and so on. It really does not reflect the actual situation of the interview. Moreover, for Ms. Baofang Xiao, the first author and responsible author of the STAP paper, I would be ashamed of my snub if I didn't even make a minimum effort such as asking questions and applying for an interview.

In any case, to be able to grasp the clues of how Xiao Baofang faces and expresses the facts is also a small gain for reporters tracking this issue. (beside the point, shortly after my notes were published, I submitted all the interview e-mails and detailed lists sent to Kobofang and Miki to my boss at that time. The Daily News Agency protested in writing to the publishing house and Obokata about the accounts such as "making people feel murderous" and "Daily News" unilaterally reporting on the leaked information. )

About two months after the notebook was published, Xiao Baofang launched the home page "STAP HOPE PAGE" that she had predicted. This is an all-English home page, in addition to other scientists' expectations for the production of STAP cells, but also contains events, production steps, charts that are considered to be part of the verification of experimental results, etc., but the bar chart of how genes related to pluripotency work in cells is significantly different from the chart published by Riken.

If scientists want to refute the doubts of the paper and the published results of verification experiments, it is not appropriate to set up an uncensored personal home page. There is no consultation address in it, and it is impossible to confirm the true intention of the home page and the original data. On the web page, there was also a notice about his doctoral thesis, which Obofang postponed the publication of his doctoral thesis on the grounds that it was "carefully studying litigation matters with relevant personnel and considering resubmitting papers to other universities."

On the Internet, there have been several reports that "STAP cells have been reproduced" by quoting papers published by foreign researchers, but each time they read the original papers, they found that the contents had nothing to do with STAP cells at all, or there were accounts of negating STAP cells.

▲ quoted papers released by foreign researchers to report the news that STAP cells were reproduced.

Others have used these misinformation, as well as Obokata's notes and web pages, as a basis, still believe that STAP cells exist, and even throw out conspiracy theories, saying that the results have been undermined by political and media forces. However, STAP cell ontology, which does not follow the basic rules of scientific procedure, should be said to have entered the field of pseudoscience.

About 145 million yen was spent on research and misconduct investigations, during which events related to previous studies involving Obokata took place. In January 2016, shortly before the publication of his notes, a paper published by Obofang et al in 2011 was withdrawn in Nature, a sister magazine of the British science magazine Nature. Other co-authors, such as the responsible author, the former chairman of the Japanese Association of Regenerative Medicine and the special professor of Tokyo Women's Medical University, Akio Okano, submitted an application to withdraw the paper.

The paper is about the performance of the cell layer used in regenerative medicine, which has been questioned on the Internet since the publication of the STAP paper in 2014. The first author is Obofang, and the co-author is Yazhi Daiwa, a professor at Tokyo Women's Medical University where Obofang studied in graduate school, and Satoshi Chang, a professor at Waseda University and instructor of Obofang's doctoral thesis. It is reported that due to many problems such as the two images in the paper are too similar, three co-authors applied to withdraw the paper on the grounds that they could not confirm the original data of the images and the experimental results. The magazine said it had tried to seek advice from the insurance company, but could not be reached.

Prior to the publication of the STAP paper, another 2011 paper by Obokata, as the first author and the basis of his doctoral thesis, was also pointed out to have used similar images many times, which was modified in 2014 because the images were "misconfigured or reused".

The huge "losses" caused by the STAP problem have also been exposed. According to the Audit Office, the total cost of STAP cell research and misconduct investigation reached about 145 million yen in the four years from 2011 to 2014. The total funding for the research of STAP cells, including labor costs, is about 53.2 million yen in the three years since 2011, including about 11.4 million yen for the interior decoration of the research room led by Obokata. A total of 91.7 million yen was spent on the two establishment of investigation committees, analysis of residual samples, consultation with legal experts, and investigation and verification of papers such as psychological care of staff. According to the Audit Institute, the main source of Riken's budget is the state operating cost subsidy, and almost all of the research and investigation funds for STAP cells come from operating fee subsidies, that is, they are paid for by taxes.

There are also "losses" that are not taken into account. That is, the time cost and experimental cost of many researchers at home and abroad who do not know the falsification of the paper, as well as the time cost of researchers who participate in the analysis of residual samples or serve as members of the investigation committee.

Fumio Matsuzaki, head of CDB, who is in charge of Riken's scientific verification, spoke of the dedicated efforts of the lab members to verify and analyze. "as researchers, in the most important period, they focus on the work that has no performance, and their gratitude is beyond words," he said. He said he himself spent 95% of his working time verifying the experiment in about 10 months in 2014. Mr. Matsuzaki said: "this is too ineffective." but now that it has happened, someone has to do it. " If only the time lost by many researchers had been spent on scientific research that was supposed to be done. I feel more and more depressed when I think about it.

How does the iPS Research Institute of Peking University deal with the falsification of papers? In my opinion, the biggest problem that Riken dealt with was that when the verification experiment was first planned and carried out, apart from two misdeeds, most of the doubts in the papers were ignored for a long time. The main authors affiliated with Liyan also called for:

"the incompleteness of the paper and the authenticity of science are two different things."

The purpose of the experiment was initially focused on "the scientific verification of the STAP phenomenon", and the meaning of the verification of the paper was added from the participation of Xiao Baofang in July. This attitude spreads the wrong impression that the incomparable nature of STAP cells is more important to find out the full picture of misconduct, and that if the verification experiment is successful, the claim of the paper will be justified. As a result, it delayed the end of the uproar and increased the cost of investigation and labour.

Indeed, "the existence of STAP cells" is the most easily understood and highly concerned topic by the society. Obofang's assertion at the press conference that "STAP cells exist" also played a role in fuelling the flames.

However, for many years, science has been developed by publishing achievements and verifying each other in the form of papers. STAP's paper itself is the only basis for the existence of STAP cells. The research institutions themselves only consider the concern of the society, so they despise the improper investigation of the paper itself, and then postpone this kind of investigation, which can be said to be a negation of the scientific mode of operation. Riyan's response completely disappointed the scientific community, and the result also led to the long-term problem. Most importantly, Riyan has lost the most important thing for research institutions, and that is "trust".

With regard to the response to scientific research misconduct, there are some examples that may become classic cases in the future, which I would like to introduce here.

In January 2018, the iPS Cell Research Institute of Kyoto University announced the fraud of the paper of Yasuhiro Yamasu, an associate professor of the institute (who was punished and dismissed in March of the same year). The content of fraud is very serious, a total of 11 images have been identified as fraud, tampering. Since then, the reporter found that the decisive factor in identifying misconduct is the restoration of the data in the laptop deleted by Shanshui.

▲ Japanese media reports on the falsification of Yasuhiro Yasuhiro papers of Kyoto University

According to Professor Hiroshi Saito, chairman of the investigation committee and deputy director of the Institute, and Professor Takahashi Takahashi and Associate Professor Yamamoto Taku, the survey first compared the histograms and other charts that make up the paper with the remaining zero-order data in the experimental measuring instruments, the primary data derived from the measured values, and the secondary data after various analyses of the primary data to determine whether the chart was made correctly. According to the rules of the institute, the primary and secondary data were submitted when the paper was submitted, and the investigation committee retained the data stored on a number of computers and hard drives used in the landscape and conducted a detailed investigation.

In many graphs, there are differences between zero-order data and primary and secondary data. It is obvious that the values have been deliberately manipulated, but there is no clear evidence of who did it. After the investigation committee found that some of the chart data were missing, it tried to recover the deleted data from the Shanshui laptop. It is said that professionals have been commissioned for this purpose, which cost about 1 million yen. The recovered data contains a number of data between the first and second times, which are considered to be traces of repeated trial and error for tampering.

The existence of these "1.5 times" data was also found in the inquiry and survey of landscapes. It is reported that Shanshui admitted that it had made a fake without the participation of others, and was eventually ruled as scientific misconduct. Professor Saito said: "We were able to verify something by restoring the data, which allowed the investigation to begin quickly." Professor Takahashi speculated:

"(the determination of misconduct) is based on both objective facts and the confession of the person concerned. Because he found traces of fraud in his laptop, so I have to admit it."

It is worth noting that in the course of the investigation, Shanshui asked for a verification experiment, but the investigation committee did not consider it necessary to conduct a verification experiment. They have maintained the trend of making a detailed survey of the basic data of the paper. Shinya Yamanaka, director of the institute, is said to have adopted this approach from the very beginning. Professor Saito explained:

"even if there is misconduct in the paper, as long as the results can be reproduced, it is not a good idea. if the data in the paper are not investigated, the investigation will drag on for a long time, causing trouble for researchers all over the world."

As has been mentioned several times, in the STAP cell incident, Obokata never submitted a laptop to write the paper. In 2006, the investigation committee found that four papers published by Professor Toby Kazunori of the University of Tokyo and Hiroaki Kawasaki's assistant (all at that time) were "non-reproducible and credible" and constituted de facto misconduct. In this case, the computer on which Kawasaki kept the experimental records was scrapped and could not be investigated. Verification experiments were also carried out in the investigation of the case.

This article comes from the official account of Wechat: non-fictional time (ID:non-fiction702), author: Sutian Taozi

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