Category Archives: Ethics

Ethics

Stem-cell fraud makes for box office success

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Posted on behalf of David Cyranoski and Soo Bin Park

Fictionalized film follows fabricated findings

Stem cell fraudster faces down the journalist who debunks him in the film sweeping Korean cinemas.

Stem-cell fraudster faces down the journalist who debunks him in the film sweeping Korean cinemas.{credit}Wannabe Fun{/credit}

A movie based on the Woo Suk Hwang cloning scandal drew more than 100,000 viewers on its opening day (2 October) and has been topping box office sales in South Korea since then. With some of the country’s biggest stars, it has made a blockbuster out of a dismal episode in South Korean stem-cell research — and revealed the enduring tension surrounding it.

The movie, Whistleblower, shines a sympathetic light on Woo Suk Hwang, the professor who in 2004 and 2005 claimed to have created stem-cell lines from cloned human embryos. The achievement would have provided a means to make cells genetically identical to a patient’s own, and able to form almost any type of cell in the body. But hopes were shattered when Hwang’s claims turned out to be based on fraudulent data and unethical procurement of eggs. The whistleblower who revealed the fraud says the new movie strays far from reality.

“This topic is sensitive, so I was hesitant when I got the first offer,” said director Yim Soon-rye at the premiere on 16 September in Seoul. “I wanted to portray him [Lee Jang-hwan, Hwang’s character in the film] as a character who faces a very human problem, and to show there is room to understand his actions.”  Although clearly inspired by the real-life events surrounding Hwang and his cloning claims, the film does not aim to be a true representation of events, but a ‘restructured fiction’ created for a movie audience.

The movie broadly traces the scandal as it actually unravelled, tracing the process through which the stem-cell claims were debunked. Some changes are made, apparently for dramatic effect: Snuppy, the Afghan hound produced by cloning in Hwang’s laboratory, was converted into Molly, also an Afghan hound, but one with cancer. When Lee sees the writing on the wall, he is shown going to a Buddhist temple where he rubs Molly’s fur, saying “I came too far … I missed my chance to stop.”

Yim says he wanted the fraudster “to be interpreted multi-dimensionally, rather than as a simple fraud or evil person”.

But rather than the scientists, Yim put the perseverance of the reporter at the centre of the film, and ends up skewing relevant facts, says Young-Joon Ryu, the real whistleblower. Ryu, who had been a key figure in Hwang’s laboratory, says his own contributions and those of online bloggers were credited to the reporter. (The discovery that Hwang had unethically procured eggs, first reported in Nature, was also credited to the reporter.)

The film has refuelled anger in some Hwang supporters who believe, despite evidence to the contrary, that Hwang did have human-cloning capabilities and that the scandal deprived the country of a star scientist. They are back online calling Ryu a betrayer.

Ryu understands that a movie might emphasize “fast action, dramatic conflicts and famous actors” to increase box office revenues. But having suffered through one perversion of the truth as Hwang made his original claims, watching the film he says that he felt was witnessing another.

Schön loses last appeal against PhD revocation

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Jan Hendrik Schön
{credit}Materials Research Society{/credit}

The German Federal Constitutional Court in Karlsruhe has confirmed on 1 October that the University of Constance was within its rights to revoke the PhD thesis of physicist Jan Hendrik Schön, who was dismissed in 2002 from Bell laboratories in Murray Hill, New Jersey, for falsifying research results.

Schön was still in his early 30s when he was dismissed after being found guilty of 16 counts of scientific misconduct.

He had worked in nanotechnology and had been considered a star scientist, able to create transistors out of single molecules. He published numerous papers in rapid succession in high-profile journals, including Nature and Science.

Two years later, following local investigations in Germany, the University of Constance decided in to revoke the PhD it had awarded to Schön in 1998. The university said that although it had no evidence that Schön engaged in wrongdoing during his PhD work, he no longer merited the degree because he had brought science into disrepute.

Schön has appealed that decision through different courts, and in 2010 a court in Freiburg ruled that he should get to keep his graduate degree. But the Federal Constitutional Court has the last word, and the university’s decision stands.

 

New details emerge on retracted STAP papers

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Posted on behalf of David Cyranoski.

New leaked e-mails showing the comments of referees for  Science and Nature provide more insight into the saga of the STAP papers, which Nature published in January and retracted in July.

The papers had promised new, simpler ways to produce stem cells by applying stress to cells taken from a patient’s tissues. But no other lab was able to reproduce the results, and experts pointed to several problems and inconsistencies in the papers. In April,  first author Haruko Obokata of the RIKEN Center for Developmental Biology in Kobe, Japan, was declared guilty of scientific misconduct; the controversy later took a tragic turn as another co-author, Yoshiki Sasai, committed suicide on 5 August.

An investigative report into the papers, released in May, revealed that a previous version of the work had been rejected by Nature, Cell and Science in 2012, before being resubmitted and accepted by Nature. (Nature’s news and comment team is editorially independent of its research editorial team.)

That report gave details from the Science referees who pointed out that one figure had been “reconstructed” in a way at odds with normal scientific practice and another one had a “suspiciously sharp” band (see ‘Misconduct verdict stands for Japanese stem-cell researcher‘).

The blog Retraction Watch posted the full comments of three referees who reviewed the paper for Science on 10 September.

The reviews include a modicum of support, but overall the paper was panned by all three. Reviewer 2 notes, “Unfortunately, the paper presents only a superficial description of many critical aspects of the work,” before launching into 21 points that “need to be addressed”, ranging from seemingly sloppy mistakes to fundamental problems with the data.

Reviewer 3 noted, “If these results are repeatable, a paradigm of developmental biology would be changed.”

The manuscript itself is not available, so it is impossible to know exactly how similar the rejected Science manuscript is to the version that was eventually published in Nature.

When the committee initially brought the problems in the Science paper to her attention, Obokata defended herself by saying that the published Nature paper had main conclusions that differed from those in the rejected Science manuscript, and she refused to show the latter to the investigative committee.

The cells in that manuscript were called stress-altered somatic cells (SAC) cells, whereas those in the paper that was eventually published bore the now-infamous name of the method: stimulus-triggered acquisition of pluripotency, or STAP. But judging from the reviewers’ comments,  STAP cells and SAC cells seem to be very similar.

Nature‘s research editors do not comment on their correspondence with authors, but on 11 September Science revealed new e-mails said to have been exchanged between Obokata and a Nature editor in April 2013.  Those e-mails allegedly quote Nature‘s reviewers as having many reservations similar to those expressed by Science‘s reviewers, and unanimously recommending that the paper be rejected — which Nature did. The Nature editor did leave open the possibility of publishing the paper if the problems were solved. About 9 months later, in December, Nature accepted both papers.

Human-rights court rules that evidence must support compassionate therapy

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Patients do not have an automatic right to a compassionate therapy for which there is no scientific evidence of efficacy, according to a landmark ruling of the European Court of Human Rights in Strasbourg, France.

The 28 May ruling referred to the case of Nivio Durisotto, whose daughter has a degenerative brain disease. He wished her to be treated with a controversial stem-cell-based therapy offered by the Stamina Foundation, based in Brescia, Italy.

But more generally, it will guide any judge facing requests from desperate patients for access to unproved therapies promoted from outside the regulated medical sector.

The judgement is yet another blow for the Stamina Foundation, whose president, Davide Vannoni, is now facing charges of fraudulently obtaining public money to support his therapy.

The Italian Medicines Agency had closed down the Stamina operations in August 2012 on safety grounds (see ‘Leaked files slam stem-cell therapy‘). In March 2013, the government issued a decree allowing patients to continue Stamina treatment if they had already begun.

Then on 11 September 2013, an expert committee appointed by the health ministry to examine the Stamina method concluded that there was no evidence to indicate that it might be efficacious (see ‘Advisers declare Italian stem-cell therapy ‘unscientific’ ‘). The committee further warned that it could be dangerous.

With encouragement from Vannoni, some patients appealed to courts for the right to treatment with the Stamina method. Some judges ruled that the treatment should be given on compassionate grounds, while others — including the judge in the Durisotto case — ruled that compassionate therapy was not justified because there was no scientific evidence of efficacy.

Durisotto brought his appeal to the European Court of Human Rights on 28 September 2013, a month after losing his case in Italy.

The European Court dismissed Durisotto’s claim, saying that the Italian court’s ruling had “pursued the legitimate aim of protecting health and was proportionate to that aim”. It further said that the Italian court’s decision had been “properly reasoned and was not arbitrary”, and that “the therapeutic value of the Stamina method had, to date, not yet been proven scientifically”. Because the case had been appropriately reasoned, it said, Durisotto’s daughter had not been discriminated against — even if some other national courts had allowed the therapy for similar medical conditions.

Munich-based patent lawyer Clara Sattler de Sousa e Brito, an expert in biomedical laws, says that this “clear ruling that scientific proof is necessary will help avoid the use of unproven therapies for so-called compassionate purposes in the future”.

 

 

US Supreme Court strikes IQ cutoff for death penalty cases

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When deciding whether a defendant is too intellectually disabled to receive the death penalty, courts must take into account inherent variability in intelligence quotient (IQ) scores, the US Supreme Court ruled today.

In its 5-to-4 decision, the court said that it is unconstitutional for states such as Florida to use an IQ score of 70 as a cutoff above which a defendant is considered to be intelligent enough to understand the consequences of his or her actions.

The plaintiff in the case, Freddie Lee Hall, has been on death row in Florida for 35 years after being convicted of murdering two people in 1978. He has taken multiple IQ tests, yielding scores ranging between 60 and 80, and testimony from people who knew him suggest that he has been intellectually disabled his entire life. But under Florida law, an IQ score above 70 disqualifies a defendant from being spared execution on the basis of intellectual disability, and Florida’s Supreme Court ruled in 2012 that Hall’s scores were too high to qualify for this reprieve.

But the American Psychological Association (APA) and the American Association on Intellectual and Developmental Disabilities hold that IQ tests have an error margin of about ten points. Consequently, Hall’s lawyers argued that IQ tests are too imprecise to determine whether his score falls on one side or the other of this cut-off.

“Florida’s rule disregards established medical practice in two interrelated ways,” Justice Anthony Kennedy writes in the court’s majority opinion. “It takes an IQ score as final and conclusive evidence of a defendant’s intellectual capacity, when experts in the field would consider other evidence. It also relies on a purportedly scientific measurement of the defendant’s abilities, his IQ score, while refusing to recognize that the score is, on its own terms, imprecise.”

The Supreme Court sent Hall’s case back to Florida’s court for a reassessment. It is not yet clear what Florida, and as many as eight other states with similar laws, will adopt in lieu of the IQ threshold. But the court’s decision compels states to incorporate other evidence if a defendant’s scores fall within the range of error.

James Harris, a psychiatrist at Johns Hopkins University in Baltimore, Maryland, and an expert on intellectual disability, is pleased with the decision. “The Supreme Court validates professional practice in measurement,” he says. “They confirm the dignity of the process and the dignity of the people with intellectual disability who are being served by the process.”

But Harris would have liked to see the ruling go further in emphasizing the importance of testing for adaptive functioning — a person’s ability to function in society — which is another factor that the APA uses to diagnose intellectual disability. This factor, he contends, is often more relevant to a case than an IQ score, which mainly tests academic ability.

Although the APA has held for decades that IQ scores have a margin of error, Justice Samuel Alito worries that the ruling opens a can of worms, as the guidelines of professional societies change over time. Tying the law to these views will “lead to instability and continue to fuel protracted litigation,” he writes in the minority opinion.  Alito adds that the court’s decision “adopts a uniform national rule that is both conceptually unsound and likely to result in confusion”.

Climate row pits academic publisher against The Times

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The Institute of Physics, a respected academic publisher, has hit back at claims in a newspaper that one of its journals declined to publish a paper because the results in it contradicted the scientific consensus on climate change.

A story on the front page of The Times in London today described how a study that “heaped doubt” on the rate of global warming was “deliberately suppressed by scientists because it was ‘less than helpful’ to their cause”. The article, which appeared under the headline ‘Scientists in cover-up of “damaging” climate view’, went on to quote an unnamed peer reviewer of the paper as saying it would be “harmful” if it were published.

The paper was written by meteorologist Lennart Bengtsson of the University of Reading, UK, and was submitted to the Institute of Physics (IoP) journal Environmental Research Letters in February. It was rejected in early March.

In response to the story in The Times, the IoP, based in Bristol, UK, released the full comments from the review. Nicola Gulley, the editorial director at the IoP, said in a statement that the rejection of the paper was based on “the content of the paper not meeting the journal’s high editorial standards”. A passage from the newspaper article has been reproduced below, alongside the section of the peer review from which it is based.

“With current debate around the dangers of providing a false sense of ‘balance’ on a topic as societally important as climate change, we’re quite astonished that The Times has taken the decision to put such a non-story on its front page,” said Gulley.

In a statement put out through the London-based Science Media Centre, Bengtsson said he did not believe that there had been a “cover up” of scientific evidence on climate change. But he added: “I was concerned that the Environmental Research Letters reviewer’s comments suggested his or her opinion was not objective or based on an unbiased assessment of the scientific evidence. Science relies on having a transparent and robust peer review system so I welcome the Institute of Physics publishing the reviewer’s comments in full.”

Earlier this month, Bengtsson was announced as having joined the Global Warming Policy Foundation (GWPF) think tank, which describes itself as “open-minded on the contested science of global warming” and is often accused of being a climate-sceptic group. However on 14 May the GWPF announced that the researcher had resigned. Bengtsson said he had been placed under “enormous world-wide pressure” from academic colleagues who objected to his link to the GWPF. He compared the situation to the McCarthy-era communist witch-hunts in the United States in the 1950s.

Benny Peiser, director of the GWPF, said his group had nothing to do with The Times story. But he added that the reviewer’s comments showed that there was a clear political dimension to the rejection.

bengt j

Misconduct verdict stands for Japanese stem-cell researcher

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Posted on behalf of David Cyranoski.

The RIKEN institute today confirmed reports out yesterday that it would turn down Haruko Obokata’s request for a re-examination of her case, and advised her to retract two Nature papers she published in January.

In the Nature papers she co-authored, Obokata, a researcher at the RIKEN Center for Developmental Biology in Kobe, presented a new method to reprogram cells to an embryonic state, which the authors called stimulus-triggered acquisition of pluripotency (STAP) (see ‘Acid bath offers easy path to stem cells‘). The papers awed other stem-cell researchers, but several problems in the data supporting the STAP phenomenon cropped up. (Note: Nature’s news and comment team is editorially independent of its research editorial team.) Based on two of those problems, a RIKEN investigative committee found Obokata guilty of scientific misconduct on 1 April.

Obokata fought back, and at a tearful press conference on 8 April announced she would appeal the judgment (see ‘Biologist defiant over stem-cell method‘).

On 7 May, the committee delivered a report detailing why they believed Obokata’s appeal should be denied. The 21-page document, available on RIKEN’s homepage (PDF, in Japanese), is a point-by-point rejections of Obokata’s defense. For example, the committee had previously deemed an image of an electrophoresis gel that had been made by combining different gel lanes as scientific misconduct. Obokata defended herself by saying that she did not intend to deceive in creating the image. But the committee obtained a review letter, from when an earlier version of the paper had been rejected by Science, that warned Obokata that such composite images need to be clearly marked. The committee concluded that Obokata had acted knowingly in making the composite image.

Today RIKEN officially endorsed this judgment. In a statement, RIKEN president Ryoji Noyori said the institute today notified Obokata and advised her to retract the STAP papers. Noyori says that the allegations of problems in the papers of the committee members would not affect the decision. “The investigation has been carried out properly,” he wrote.

German research agencies condemn animal-rights attack on neuroscientist

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A timid silence often follows public attacks on scientists who use animals in their research. But today a group of ten heavyweight academic organisations in Germany shed its habitual reserve and raised a stern collective voice against animal-rights activists whose recent advertising campaign targeted an individual neuroscientist.

The activists overstepped the line between freedom of expression and unacceptable defamation, said the group, known as the Alliance of Science Organisations, which includes the Max Planck Society, the DFG grant-giving agency, the Conference of University Rectors and the German National Academy of Sciences Leopoldina. In particular, it said, activists depicted Andreas Kreiter, who uses monkeys in his research, as ‘not quite human’.

The row began on 16 April, when the Tierversuchsgegner Bundesrepublik Deutschland (Opponents of Animal Experiments Federal Republic of Germany) placed an aggressive full-page advertisement in two national quality newspapers and three regional newspapers.

The advertisement comprised a long treatise against animal research. It focused on Kreiter, from the University of Bremen, but also called on “all citizens” to treat every animal experimenter “with contempt and to denounce their work publicly”.

Its headline read “Kreiter cold-bloodedly carries on”, a reference to a federal court’s recent decision that local authorities in Bremen acted illegally in trying to stop his research. This legal decision had led Kreiter to believe his 16-year struggle to continue his studies into mechanisms of attention, one of the pillars of consciousness research, had finally ended. In the late 1990s Kreiter and his family had to be placed under police protection.

The advertisement set Kreiter’s photograph next to a picture of a primate with a number tattooed onto its chest, and with its head secured against movement during an experiment. It claimed that Kreiter’s experiments cruelly torment primates without yielding any medical advances.

This personalisation of the animal debate helped to spur the Alliance into action, as did the advertisement’s provocative opening quotation, attributed to neurologist and animal protectionist Herbert Stiller: “Animal experimenters are a particular type of creature – one should not casually call them human.”

The citation also precipitated an unprecedented debate in the press, because the right to human dignity is considered sacred in Germany and is enshrined in the first article of the country’s post-war constitution. During the Nazi era, categories of people like Jews, gypsies or the handicapped were declared to be ‘sub-human’ and killed.

In its public statement, the Alliance “expressly and decisively condemns” the advertisement. It says that animal research is necessary and is carried out under the tight contol of the authorities.

Welcoming the Alliance’s first public defence of animal research, neuroscientist Stefan Treue, director of the German Primate Centre in Göttingen, says that the affair “reinforces the recognition of the scientific community that we really need a public information platform where citizens and journalists can learn the facts about why animal research is needed”.

Kreiter says he is disappointed that the debate around his work has been reactivated. “This type of attack is hardly new for me,” he adds. “But these advertisements were particularly aggressive.”

 

 

Investigator of controversial stem-cell study resigns

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The head of a Japanese committee investigating claims that stem cells could be made using mechanical stress or acid resigned from the committee today over anonymous allegations that at least one of his own papers contained problematic data. He says he resigned out of concern that the incident could complicate the current investigation.

Shunsuke Ishii, a molecular biologist at the RIKEN Advanced Science Institute in Tsukuba, was leading a team looking into two papers that reported a new kind of pluripotent stem cells — called STAP cells — in Nature on 30 January. The papers, whose first author was Haruko Obokata of the RIKEN Center for Developmental Biology in Kobe, were found to contain problems, including gel lanes that had been spliced together such that different lanes looked as though they were part of the same experimental procedure.

In a report released on 1 April, the committee deemed that two of the problems — the spliced gel lanes and the use of an image that had appeared in Obokata’s dissertation to represent a different experimental finding — constituted misconduct. Obokata appealed the judgment, and she has delivered supplementary materials in response to a request by the committee. Now the committee is deciding whether to reopen the case.

On 24 April, an eight-page document alleging problems in two papers Ishii co-authored in 2004 and 2008 was posted anonymously and widely circulated. The alleged problems included gel lanes that were spliced and set next to each other, without clear indication that splicing had taken place.

Ishii responded on the same day with a post on his laboratory’s homepage. The first paper in question is a 2008 study of a tumour suppressor and published in Oncogene (Oncogene is published by the Nature Publishing Group, which hosts this website; Nature’s news and comment team is editorially independent of Nature Publishing Group journals’ research editorial teams.) Ishii confirmed that the order of the gel lanes was changed to align with the explanation in the text and that errors were made when making that alignment. But he insists that the data were all part of the same experiment. In his post he includes copies from the notebooks showing the original data for the experiments. He also includes a correction that, he says, the editor of the journal has already accepted. “These changes do not affect any of the results or conclusions of our study,” reads the correction.

Today, Ishii supplemented the post with explanatory materials to address the problems raised about the second paper, a 2004 article in Journal of Biological Chemistry. He says that different gel lanes in that paper were juxtaposed for “space saving”, and he provides clearly marked original data. He says this presentation was “not a problem, according to the rules ten years ago”.  He acknowledges, however, that “stricter rules now” require a clear line indicating when gel lanes are not in their original setting. He is not seeking a correction for this paper.

Some researchers have criticized Ishii, saying that if splicing of gel lanes counted as misconduct for Obokata, it should also count as misconduct in his case. Obokata’s lawyer cites the Ishii case to argue for a reinvestigation of her own.

One difference in Obokata’s case, however, is that the gel lanes were not only spliced, they were also stretched and rotated, showing a greater degree of manipulation. Also, according to the committee, Obokata’s laboratory notes lacked a clear indication of the path from original data to published data.

RIKEN says that it is now gathering information to decide whether to launch an investigation into Ishii’s research. This preliminary investigation should take about a week, according to a RIKEN spokesperson.

Today Ishii announced his resignation from the committee investigating Obokata’s papers. In a written statement, he says the “copies of laboratory notes and original experimental data [posted on the laboratory homepage] clearly show that no misconduct was involved” in the two papers.

Discrimination starts even before grad school, study finds

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biased-teaching-natureMost would acknowledge that women and minorities already face more hurdles in academia than their white, male peers. A lack of mentors, occasionally overt discrimination and the academy’s poor work-life balance, are well-documented issues. But now a study has suggested that these groups may be at a disadvantage even before the starting whistle sounds.

A study published on 22 April (and currently under review) looked at how likely faculty were to respond to a request to meet with a student to informally discuss potential research opportunities — a scenario picked as a proxy for the many informal events that could boost an academic career and which fall outside institutions’ formal checks and balances. They found — overwhelmingly — that professors of all groups were more likely to respond to white men than women and black, Hispanic, Indian or Chinese students. Academics at private universities and in subjects that pay more on average were the most unresponsive.

Katherine Milkman at the University of Pennsylvania in Philadelphia, along with colleagues Modupe Akinola of Columbia University in New York and Dolly Chugh of New York University, sent fake e-mails to 6,548 professors at 259 US institutions, pretending to be students wanting to discuss research opportunities before applying to a doctoral programme. The messages were identical, bar their fictional authors, whose names were picked for being recognizable by gender and ethnicity — ‘Steven Smith’ representing a white male, for example, and ‘Latoya Brown’ for a black female.

White men were more likely than women and minorities to receive a reply in every discipline except the fine arts, where the bias was reversed (see ‘Biased teachings’ above). Business showed the greatest disparity, with 87% of white males receiving a response compared to just 62% of female and minority students. In the sciences, faculty in engineering and computer sciences, life sciences and natural, physical sciences and maths all showed significant biases against minorities and women.

Broken down by group, the results were more nuanced. Asian students experienced the greatest bias, despite research showing that stereotypes about Asians in academia are generally positive, says Milkman. Among private university faculty the response rate for white men was 29 percentage points higher than for Chinese woman — the greatest disparity observed. Meanwhile in the natural and physical sciences and maths there was a small, though not statistically significant, bias in favour of Hispanic women.

The study found no relationship between representation of any group among faculty in a given discipline and the degree of bias that students faced when trying to interact with them. This means the findings cannot be attributed to the largely white, male academy preferring to associate with others like them, says Milkman. “One of our hypotheses was that more diverse departments would be less biased and we just don’t see it,” she adds. The only exception was among Chinese faculty, who were less likely than other faculty to discriminate against Chinese students.

Curt Rice, a professor at the University of Tromsø in Norway and head of Norway’s Committee for Gender Balance in Research, says that the result that women and minorities are as biased as white men is not surprising. They mirror a 2012 study, by researchers at Yale University in New Haven, Connecticut, which showed that science faculty of both sexes show unconscious biases against women in hiring and pay decisions. The problem — says Rice — is implicit rather than explicit bias. “We’re talking about the absorbed effect of cultural stereotypes that lead to the formation of biases,” says Rice. “It’s no surprise they’re held by all of us because they’re subconscious and the result of cultural stereotypes that we’re all exposed to.”

Comparing results across disciplines, the team found more intriguing effects. The more highly paid faculty are on average (by subject), the greater the difference in response rate between white male and other students. “For every US$13,000 increase in salary, we see a drop of 5 percentage points in the response rate when compared to Caucasian males,” says Milkman. She links the finding to studies that recently found that wealthy, high-status people tended to be less empathetic and more self-focused. Biases were also more prevalent in private institutions than public ones, she adds.

Although the study looks at only one tiny step in the path to a successful academic career, Rice thinks the compound effect of many situations like it could well help explain why we find so few women and people from minority backgrounds at professor level. Milkman agrees: “This is a small moment — it’s one time someone’s reaching out and looking for guidance and encouragement. But if every time you do this happens to you, that’s going to add up.”