Haruko Obokata

Haruko Obokata (小保方 晴子, Obokata Haruko, born 1983) is a former stem-cell biologist and research unit leader at Japan's Laboratory for Cellular Reprogramming, Riken Center for Developmental Biology.[3][4] She claimed to have developed a radical and remarkably easy way to make stimulus-triggered acquisition of pluripotency (STAP) cells that could be grown into tissue for use anywhere in the body.[5] Riken, however, eventually launched an investigation in response to allegations of irregularities in images appearing in several articles she authored, including the paper announcing the discovery of STAP cells.[6][7][8] The ensuing scandal in 2014 over STAP cells has since become one of the world's best-known scientific frauds alongside the Schön scandal and Hwang Woo-suk's cloning experiments.[9][10][11][12][13]

Haruko Obokata
Born (1983-09-25) September 25, 1983
Matsudo City, Chiba Prefecture, Japan[1]
NationalityJapanese
Alma materWaseda University
Known forSTAP cells
Scientific career
FieldsStem cell research
InstitutionsRIKEN
ThesisIsolation of pluripotent adult stem cells discovered from tissues derived from all three germ layers (2011 (revoked in 2015))
Doctoral advisorSatoshi Tsuneda[2]

Early life and education

Obokata was born in Matsudo, Chiba, Japan, in 1983. She attended Toho Senior High School, which is attached to Toho University, and graduated from Waseda University. At Waseda University, Obokata undertook undergraduate studies in the Department of Applied Chemistry, within the School of Science and Engineering, earning a Bachelor of Science in 2006, and graduate studies in the Graduate School of Advanced Science and Engineering, earning a Master of Science in applied chemistry in 2008.

After completing her master's, Obokata went on to study stem cells and regenerative medicine at the Institute of Advanced Biomedical Engineering and Science, a cooperative research and education facility operated with Tokyo Women's Medical University. She then undertook research at Harvard Medical School in Cambridge, Massachusetts under Charles Vacanti for two years. Vacanti had hypothesized that stem cells could be created under certain conditions, and Obokata, according to a profile in The New Yorker by Dana Goodyear, ‘was a lab director’s dream’, applying herself to the challenge ‘with fanatical devotion’. A research assistant, Jason Ross, told Goodyear, ‘I’ve never met anyone smarter.’ Obokata’s thesis adviser ‘told Vacanti that it was the best thesis he had ever read.’[14]

In 2011, Obokata returned to Japan to complete her Ph.D. in Engineering at the Graduate School of Advanced Engineering and Science at Waseda University.[15][16] According to an Asahi Shimbun news report, Obokata had offered to retract her doctoral dissertation following allegations that she may have copied and pasted some segments of her dissertation from publicly available documents posted in the U.S. National Institute of Health website.[17]

In October 2014, an investigative panel appointed by Waseda University gave Obokata one year to revise her Ph.D dissertation or lose her degree.[18] One year later, Waseda University announced that it was revoking Obokata's Ph.D.[19]

Career

Obokata became a guest researcher at the Riken Center for Developmental Biology in 2011, and she was appointed as head of the Lab for Cellular Reprogramming in 2013.[20][21]

At Riken, Obokata continued her work on stem cells, collaborating with Wakayama and, at a distance, with Vacanti. After a paper about the purported stem-cell discovery was rejected in 2012 by three of the most prestigious scientific journals, Nature, Cell, and Science, Obokata teamed up with Yoshiki Sasai, with whom she performed further experiments. A revised paper was resubmitted to Nature along with a separate, related paper. In December 2013, Nature accepted both papers. Before their publication, in a note to Vacanti, Sasai seemed to give Obokama the bulk of the credit for the achievement, saying that she had discovered ‘a magic spell’ that resulted in the experiment’s success.[22]

In 2014, she published the following two papers in the journal Nature, one of the world’s leading science periodicals:

  • Obokata, Haruko; Wakayama, Teruhiko; Sasai, Yoshiki; et al. (2014). "Stimulus-triggered fate conversion of somatic cells into pluripotency". Nature. 505 (7485): 641–647. doi:10.1038/nature12968. PMID 24476887.
  • Obokata, Haruko; Sasai, Yoshiki; Niwa, Hitoshi; Vacanti, Charles A.; Andrabi, Munazah; Takata, Nozomu; Tokoro, Mikiko; Terashita, Yukari; Yonemura, Shigenobu; Wakayama, Teruhiko (January 30, 2014). "Bidirectional developmental potential in reprogrammed cells with acquired pluripotency". Nature. 505 (7485): 676–680. Bibcode:2014Natur.505..676O. doi:10.1038/nature12969. PMID 24476891.

In the articles, Obokata and her colleagues claimed to have discovered, in the words of a later account in The Guardian, ‘a surprisingly simple way of turning ordinary body cells…into something very much like embryonic stem cells’ by soaking them in ‘a weak bath of citric acid.’ This procedure, the scientists maintained, ‘washed am way their developmental past,’ transforming them, as it were, into ‘cellular infants, able to multiply abundantly and grow into any type of cell in the body, a superpower known as pluripotency.’

Upon the publication of the articles, Obokata "was hailed as a bright new star in the scientific firmament and a national hero" and a potential Nobel Prize winner.[23]

"Here, theoretically, was a never-ending supply of super-versatile custom stem cells, free of ethical baggage. By 2020, according to the consulting firm Frost & Sullivan, stem-cell therapies will be a forty-billion-dollar global industry. STAP seemed to be a bridge to long-held goals of patient-specific drug development, advanced disease modelling, and, ultimately, the ability to regenerate body parts without the risk of immune-system rejection. Sasai compared STAP to Copernicus’s reorganization of the cosmos."

"A brilliant new star has emerged in the science world," stated an editorial in the Asahi Shimbun. "This is a major discovery that could rewrite science textbooks." Obokata encouraged the media’s focus on her at the expense of her collaborators, and presented herself as having come up with the whole idea for STAP. She said, for example, that she had experienced a ‘Eureka moment’ that had actually occurred to Vacanti.[24]

Controversy

Within a few days of publication of the Nature articles, ‘disturbing allegations emerged in science blogs and on Twitter. Some of her images looked doctored, and chunks of her text were lifted from other papers.’[25] Professor Teruhiko Wakayama, a senior author of the Nature articles, proposed retracting the papers and re-submitting them if the findings could be reproduced. The Japanese government affiliated research institute Riken also launched an investigation into the issue. Stem cell critics also noted that the images in the published articles are very similar to those published in Obokata's doctoral thesis, which were from a quite different project than the Nature publications.[26] On April 1, Riken announced that it had found Obokata guilty of scientific misconduct on two of the six charges initially brought against her.[27] The Riken investigators reached the following conclusion:

In manipulating the image data of two different gels and using data from two different experiments, Dr. Obokata acted in a manner that can by no means be permitted. This cannot be explained solely by her immaturity as a researcher. Given the poor quality of her laboratory notes it has become clearly evident that it will be extremely difficult for anyone else to accurately trace or understand her experiments, and this, too, is considered a serious obstacle to healthy information exchange. Dr. Obokata’s actions and sloppy data management lead us to the conclusion that she sorely lacks, not only a sense of research ethics, but also integrity and humility as a scientific researcher.[28]

Obokata apologised for her "insufficient efforts, ill-preparedness and unskilfulness", among other things, but insisted that she had only made "benevolent mistakes"; she denied entirely the charge that she had fabricated results and professed shock at the charge that she lacked ethics, integrity, and humility. She also insisted that her Stap cells actually did exist. "Initially her collaborators stood firmly by her," reported The Guardian, "but one by one they relented and asked Nature to retract the articles."[29] Finally, on June 4, 2014, Obokata agreed to retract both the papers published in Nature in early 2014.[30] Nature confirmed the retraction on July 2.[31][32] At about this time, "genetic analysis showed that the Stap cells didn’t match the mice from which they supposedly came." Although Obokata claimed not to know how this was possible, "the obvious, and rather depressing, explanation is that her so-called Stap cells were just regular embryonic stem cells that someone had taken from a freezer and relabelled."[33]

In July 2014, Obokata was allowed to join Riken's efforts to verify her original results under monitoring by a third party. She tried to replicate her own study using genetically manipulated mouse spleen cells that glow green if a gene indicative of pluripotency is activated. She failed to reproduce the ‘STAP cell’ to back up her claimed discovery.[34]

As a result of this scandal, Riken’s deputy director, Yoshiki Sasai, who was Obokata’s mentor, supervisor, and co-author, described himself as ‘overwhelmed with shame’.[35] He spent a month in hospital, then, on August 5, 2014, committed suicide.[36] He had been cleared of misconduct, but also had been criticized for inadequate supervision of Obokata.[37]

Obokata announced her resignation from Riken in December 2014.[38][39] ] In a year-end final report on the scandal, Riken concluded that she had indeed ‘falsified and fabricated data, that her so-called Stap cells were actually embryonic stem cells, and that the mixup was probably not accidental.’ Although Riken cleared her senior co-authors of ethics violations, it did criticize them severely for a failure to oversee her work sufficiently. Riken also ; however, it gave them a brutal drubbing for not properly checking her work. Riken also ‘promptly set about overhauling the CDB from top to bottom, stripping away half of its 500-odd staff, renaming it and installing a new management team.’

In a February 2015 article, The Guardian stated that she was guilty of ‘unbelievable carelessness,’ having ‘manipulated images and plagiarised text’ in a highly inept fashion. The Guardian also described her as exhibiting hubris: ‘If Obokata hadn’t tried to be a world-beater, chances are her sleights of hand would have gone unnoticed and she would still be looking forward to a long and happy career in science. Experiments usually escape the test of reproducibility unless they prove something particularly important, controversial or commercialisable..By stepping into the limelight, she exposed her work to greater scrutiny than it could bear.’[40]

In September 2015, Nature published a paper by George Daley that 'documented the failed attempts of seven labs to validate the claims of Obokata and her collaborators.'

In 2016, Obokata's book 'Ano hi' (あの日- 'That Day') was published by Kodansha, who considered it 'an important record by someone whose side of the story has not yet been heard', and saying '“We think it’s meaningful to publish the views of Ms. Obokata herself to investigate the causes of confusion over the STAP cells”'. In this account of the controversy, Obokata relates 'her association with, and then estrangement from, onetime boss Teruhiko Wakayama, a former Riken researcher who now teaches at Yamanashi University', asserting that 'crucial parts of the STAP experiments were handled only by Wakayama' and alleging that 'he changed his accounts of how the STAP cells were produced.' Claiming to have received the cells used in the experiments from Wakayama, Obokata directs suspicions at him instead.[41] The book became the #1 bestseller on Amazon Japan. At around the time her book appeared, she wrote to Dana Goodyear of the New Yorker. ‘I feel a strong sense of responsibility for the STAP papers,’ she stated. ‘However, I want you to know I never wrote those papers to deceive anyone.’ Obokata ‘insisted that STAP was real.’[42]

In March 2016, Obokata launched a new website, stap-home-page.com, at which she expressed her ‘deep remorse and heartfelt apology over the STAP papers which were published in Nature in 2014,’ stated that she was ‘ashamed of my careless mistakes,’ and averred that the purpose of the website was ‘to provide the information to the scientific community that may allow for solid proof of the production of STAP cells to be achieved.’ She added that she was ‘still under medical treatment for mental and physical depression from this incident.’ As of March 2019, the page had not been substantially updated.[43]

A short essay by Obokata appeared in the May 17, 2018, issue of Shukan Bunshun magazine. In the essay she wrote about her new book, The Diary of Haruko Obokata, which covers her life from December 2014 to October 2016, and described herself as ‘a person who has been hounded.[44]

gollark: Send different Content-Type headers?
gollark: ???
gollark: That's more of a security thing than a privacy thing.
gollark: That's because you're worrying they might be leaked, isn't it?
gollark: I think this is at least partly because of the fear that they *might* be.

See also

References
  1. "STAP cell pioneer nearly gave up on her research". The Asahi Shimbun. January 30, 2014. Archived from the original on January 30, 2014.
  2. "Obokata had free way of thinking since childhood". The Japan News. Yomiuri Shimbun. February 2, 2014. Retrieved February 3, 2014.
  3. Cyranoski, David (January 29, 2014). "Acid bath offers easy path to stem cells". Nature. 505 (7485): 596. Bibcode:2014Natur.505..596C. doi:10.1038/505596a. PMID 24476866.
  4. "Laboratory for Cellular Reprogramming". RIKEN.
  5. "Stem cell 'major discovery' claimed". BBC. January 29, 2014.
  6. "Research institute probes 'irregularities' in images associated with STAP cell discovery". Mainichi. February 15, 2014.
  7. "On the articles of Haruko Obokata, who discovered STAP cells". stapcell.blogspot.com. February 13, 2014.
  8. Vacanti, Charles A.; Yamato, Masayuki; Niwa, Hitoshi; Vacanti, Martin P.; Kojima, Koji; Sasai, Yoshiki; Wakayama, Teruhiko; Obokata, Haruko (February 13, 2014). "PubPeer : "Stimulus-triggered fate conversion of somatic cells into pluripotency"". pubpeer.com.
  9. "From stem cells to physics fraudulent science results are plenty but hard to find". Deutsche Welle. June 6, 2014. Retrieved June 6, 2014.
  10. "Stem cell debacle déjà vu". Bio Edge. April 6, 2014. Retrieved April 6, 2014.
  11. "STAP論文を「世界三大研究不正」の1つに認定". 日経BPネット. June 13, 2014. Retrieved June 13, 2014.
  12. "STAP細胞が『世界３大研究不正』とされた衝撃". Yahooニュース. June 14, 2014. Retrieved June 14, 2014.
  13. "科学界の「世界の三大不正」とは？小保方晴子氏問題、「シェーン事件以上」との指摘も". newclassic. June 15, 2014. Archived from the original on June 15, 2014. Retrieved June 15, 2014.
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  15. "Profile of Riken scientist Obokata". NHK. January 30, 2014. Archived from the original on February 3, 2014.
  16. "Waseda graduate finds new method to create stem cells: Haruko Obokata leads research team". Waseda University. January 30, 2014.
  17. "STAP cell scientist seeks to withdraw Ph.D. thesis" Archived April 7, 2014, at the Wayback Machine. The Asahi Shimbun. March 16, 2014.
  18. Momoko, Suda, " Archived November 9, 2015, at the Wayback Machine", "Mainichi Shimbun", 30 October 2015
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  20. "'Rikejo' scientist triumphed over setbacks". The Japan News. The Yomiuri Shimbun. January 31, 2014. Archived from the original on February 3, 2014.
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  28. Ishii, Shunsuke et al. (March 31, 2014) Report on STAP Cell Research Paper Investigation. riken.jp
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  31. Lawrence, Janet (July 2, 2014). "Nature journal retracts stem cell paper citing "critical errors"". Reuters. Retrieved July 2, 2014.
  32. McNeil, David (June 30, 2014) "In Japan, Research Scandal Prompts Questions". Chronicle of Higher Education
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  38. Gallagher, James (December 19, 2014). "Stem cell scandal scientist Haruko Obokata resigns". BBC News. Retrieved December 19, 2014.
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