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How Japan's stem cell study became a scandal

Pioneering research on stem cells in Japan took a series of bizarre turns.

Last updated: 08 Jul 2014 13:02
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Haruko Obokata, a 31-year-old scientist became an overnight media star in Japan after the publication of her research on stem cells [AFP]

Tokyo, Japan - When researchers made the announcement earlier this year, scientists around the world were stunned and thrilled in turn. A Japanese scientist had discovered a radical new method to transform ordinary cells into potent stem cells - the cell with the ability to become any other cell types.

However, the thrill quickly faded as the serious questions were raised over the research methodology - even though the discovery was at the time considered a breakthrough in advancing regenerative medicine and the replacement of diseased organs.

Haruko Obokata, a 31-year-old scientist, became an overnight media star in Japan, and not just for her game-changing discovery of stimulus-triggered acquisition of pluripotency (STAP) cells, which she claimed had the ability to turn into any type of cell in the body.

The press made much of Obokata's stylish appearance, noting her distinctive touches in the laboratory - such as having the lab walls painted pink and yellow; and her choice of wearing a kappogi, a Japanese sleeveless cooking smock instead of a white lab coat, which sent sales of the garment soaring.

Her fame continued to rise, that is until her research came under scrutiny.

Black eye for science

The new method was described in two papers written by Obokata, the lead author, and colleagues at Japan's RIKEN Center for Developmental Biology (CDB) and other institutions, and published online by the journal Nature on January 29. The procedure astonished scientists around the world because it ran counter to most assumptions on cell biology and was far simpler than existing methods for obtaining stem cells.

It's contributing to a broader, harmful perception that stem cell research is disproportionately linked to controversy and scandals.

- Paul Knoepfler, University of California, Davis 

But the story took a turn after a number of bizarre twists, including charges of research misconduct that resulted in Nature retracting the article on July 2.

The outcome is another black eye for science and stem cell research in particular.

"It's contributing to a broader, harmful perception that stem cell research is disproportionately linked to controversy and scandals," Paul Knoepfler, an associate professor in the Department of Cell Biology and Human Anatomy at the University of California Davis School of Medicine, told Al Jazeera.

"Stem cell research will increasingly impact the public," says Knoepfler, who was one of the first to raise questions about the Obokata research the day the papers were published.

"So they need to know what it is all about, be educated on the risks, have realistic hopes."

Problems with the papers

In an audio interview with Nature accompanying the papers on January 29, Obokata, then team leader of a group of CDB researchers in Kobe, described what inspired her research.

Certain plants - for example, a carrot - can produce stem cells from mature cells when "exposed to strong external stresses like dissection," she explained. "I instinctively felt that we may have similar mechanisms to the plant."

To investigate, she subjected blood cells of week-old mice to a number of different stresses such as pressure and starvation. Eventually, she was able to shrink some cells and return them to their original stem-cell state after bathing them in a mildly acidic solution. To prove their potency, she used these STAP cells to form parts of baby mice and even an entire mouse embryo.

But the limelight shining on Obokata turned into a spotlight of interrogation when the peer review process kicked in.

Scientists subject all new ideas and discoveries to examination and testing, and they soon found problems with the Obokata papers, including a manipulated image and alleged plagiarism.

RIKEN, Japan's largest government-affiliated research institute, opened an investigation into the allegations after sufficient public backlash. Its findings concluded that there was "research misconduct by Dr Obokata on two points". She was found to have manipulated two images to create a false composite image, and she used data from her doctoral thesis, even though it was derived under different conditions to those described in her STAP papers.

Refusing to retract

A tearful Obokata held a press conference in Osaka on April 9 to apologise for her research infractions. However, she maintained they were a result of her inexperience and not meant to mislead. Before massed reporters, she insisted the research was accurate and data existed to prove it. She opposed retracting the papers.

Supporting her was Charles Vacanti, head of anaesthesiology at Brigham and Women's Hospital/Harvard Medical School and a senior author of one of the papers.

Obokata had earlier worked in his lab on similar research. In an email to the Boston Globe defending Obokata's discovery Vacanti wrote: "While the investigation determined there were errors and poor judgement in the development of the manuscript, I do not believe that these errors affect the scientific content or the conclusions."

The story took yet another extraordinary turn when Shunsuke Ishii, a RIKEN Distinguished Senior Scientist and chair of the Obokata investigation committee, resigned from the committee on April 25, after acknowledging he, too, had manipulated images in papers he had previously published.

A statement from RIKEN said it accepted his resignation and had launched an investigation into the matter.

An independent reform panel established by RIKEN called for drastic action against Obokata and the CDB. As reported in the Japan Times on June 13 the panel concluded that Obokata be severely punished and that the CDB be disbanded.

To make matters worse, a worried co-author of the papers, Teruhiko Wakayama, formerly with RIKEN and a member of Obokata's team, sent some of the STAP cell samples he had kept frozen to two outside labs for genetic analysis. In June, Wakayama told reporters the analysis confirmed that the STAP cells he had were not, as purported, created from the mouse blood cells he had supplied to Obokata to conduct the experiment.

A blow to public perception

This is a good time to seriously question what science is and what science is for.

- Noriko Osumi, Center for Neuroscience at Tohoku University School of Medicine

This is not the first furore involving stem cell research. In 2005, an even bigger scandal rocked the science community when Hwang Woo Suk, a celebrated South Korean stem cell pioneer, was exposed for having fabricated research that claimed to have cloned human stem cells.

According to Noriko Osumi, director of the Center for Neuroscience at Tohoku University School of Medicine, such instances damage the public's perception of stem cell research in general.

"It is very important to maintain public trust in science in Japan because most of the funding comes from the government, which means research activity is supported by our tax money," Osumi told Al Jazeera.

"Scandals like STAP undermine public trust," she added.

"Considering the results from Wakayama and RIKEN, I believe STAP cells never existed," Osumi said. "If someone wanted to produce results to fit a beautiful STAP cell story, there are many labs in RIKEN CDB where those ES cells exist." She added: "This is a good time to seriously question what science is and what science is for."

Biologist Knoepfler, another non-believer in STAP cells, concurred. "We may never know the truth," he said. "But the STAP scandal is an opportunity for self-examination, though the people who could probably benefit the most from some introspection are the least likely to want to engage in that. They want this thing to go away and as fast as possible."

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Source:
Al Jazeera
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