Category Archives: Health and medicine

Health and medicine

WHO postpones decision on destruction of smallpox stocks — again

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The stalemate continues over the question of when to destroy the last stocks of the virus that causes smallpox, a killer disease that was eradicated in 1980. One of the World Health Organization’s (WHO) two advisory committees on smallpox supports the stocks’ destruction, and the other opposes it. Last weekend, health ministers of the WHO’s 194 member states again postponed a decision and decided to set up a third WHO smallpox advisory committee in a bid to broker a consensus.

The issue came up again on the agenda of the annual meeting of the World Health Assembly, the WHO’s top decision-making body, which was held in Geneva, Switzerland, from 19 to 24 May. It was last discussed at the 2011 assembly, which reaffirmed that the stocks of the variola virus should be destroyed but deferred to this year’s meeting discussion on any date of destruction.

A central question remains whether research of public-health importance is still needed on the virus, or whether the last stocks should be destroyed to eliminate the threat of an accidental release from the two labs where they are held — at the US Centers for Disease Control and Prevention in Atlanta, Georgia, and the Russian State Research Center of Virology and Biotechnology in Koltsovo, near Novosibirsk.

The final agenda of this year’s meeting, however,  asked ministers only to take note of a WHO update report to the assembly on progress on completing needed research. The WHO’s ‘advisory committee on variola virus research’ (ACVVR), which oversees and approves any research using the stocks, felt that live virus was no longer needed to develop diagnostics and vaccines, but was still needed to develop antiviral drugs. By contrast, its ‘advisory group of independent experts to review the smallpox research programme’ (AGIES) felt that there was no research justification for holding on to the stocks.

Although the ACVVR reached a consensus on antivirals, there was considerable debate about this among its members. Some argued, for example, that with two promising drugs — tecovirimat and brincidofovir — close to licensing, virus stocks were no longer needed. Others felt that the virus should be kept in case these drugs failed to get licensed, requiring the development of other compounds.

The AGIES considered the same issues but swung towards virus being no longer needed to develop antivirals — it also suggested that should a future need arise to develop new drugs, live virus could in any case be recreated from viral DNA. The ACVVR is often perceived as being more focused on research interests, and the AGIES on public-health aspects.

By the time the WHO assembly got to discussion of destruction of smallpox stocks, it was near the end of the last day of the meeting. It quickly became clear that there were sharply divided opinions and no consensus, according to Glenn Thomas, a WHO spokesman. The decision to setup a third expert group is intended to bring together a mix of scientists and public-health and other experts to review all the elements of the debate and take the issue forward, says Thomas.

For the moment, the precise terms of reference of the group, or its composition, have yet to be decided. The latter will be important, as the destruction of the variola stocks is also a political issue. The United State is strongly opposed to destruction of the virus stocks, largely because — like many other developed countries — it wants to pursue research that it believes might help to protect against a bioweapons attack by rogue states or terrorists, who may have access to undeclared stocks (see ‘WHO to decide fate of smallpox stocks‘).

Some scientists are also keen for smallpox research using live virus not to be stopped, but continued and expanded. Two members of the ACVVR, Clarissa Damaso, of the Federal University of Rio de Janeiro in Brazil, and Grant McFadden, of the University of Florida in Gainesville, have argued, for example, that the WHO’s restricting of smallpox research to tightly circumscribed public-health applications has limited fundamental research that could advance public health. In an opinion piece published 1 May in the journal PLoS Pathogens, along with Inger Damon, head of the poxvirus and rabies branch of the Centers for Disease Control and Prevention in Atlanta, Georgia, they argue that: “the research agenda with live variola virus is not yet finished and that significant gaps still remain”.

But the majority of the health ministers of the WHO member states — including those of many poorer countries, who view the risks of an accidental release as outweighing any research benefits — want the stocks of virus destroyed at some point. The question for the WHO assembly is, as always, when? But yet again, it has kicked that can down the road.

European Commission rejects petition on embryonic stem cells

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The European Commission has, as predicted, turned down a request from more than 1.7 million citizens for new legislation to ban the funding of research using human embryonic stem cells, including those that do not involve destruction of new embryos.

Scientists are relieved. “It is a good decision for us and for Europe,” says stem-cell researcher Elena Cattaneo of the University of Milan, Italy, who works on Huntington’s disease. But One of Us, the organization that led the petition, claims on its website that the Commission has exercised an “unjustifiable veto which flouts the democratic procedure”.

The One of Us petition was among the first to be presented within the Commission’s new European Citizens’ Initiatives (ECIs) scheme, launched two years ago in a bid to widen participatory democracy. The ECIs have drawn criticism for their potential to be exploited by pressure groups wishing to reopen recently closed debates. (Nature‘s editorial pages joined the critics: see ‘The democracy carousel‘.)

Any ECI that can muster more than 1 million signatures across at least seven European Union countries automatically triggers a parliamentary hearing and a formal response from the Commission.

The parliamentary hearing for the One of Us initiative took place on 10 April.

Today the Commission published its reasoning for not proposing new legislation. It said that the EU Council of Member States and the European Parliament had last year debated the issue thoroughly, and no new information was available to warrant a return to the debate so soon. At the time, member states and parliament both agreed that stem-cell research held great promise for currently incurable diseases such as Parkinson’s disease, and it was thus in the public interest to support it. They also agreed that human embryonic stem cells are still sometimes required in such research.

In its statement, the Commission further pointed out that its funding rules already preclude active destruction of new embryos and require strict oversight of experiments.

The petitioners had referred to a 2011 judgement of the European Court of Justice, which ruled that patenting of inventions involving cells derived from human embryos was illegal. But the Commission said that ruling did not apply to research.

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”.

‘Misreading’ of data led to errors in statin papers

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The BMJ is modifying, and is considering whether to retract, articles that questioned whether many patients should be given cholesterol-lowering statin drugs. The articles made a critical statement about the rate of side effects that were based on a “misreading” of another study, according to the journal’s editor-in-chief Fiona Godlee.

In October 2013,  John Abramson, a medical researcher at Harvard University in Cambridge, Massachusetts, and his colleagues stated in a review article that around one-fifth (18–20%) of patients on statins experienced side effects. The authors’ main thrust was to re-analyse data by the Cholesterol Treatment Trialists’ (CTT) Collaboration, and they cite evidence that there are no benefits when statins are given to people at low risk of cardiovascular disease — a controversial issue in medicine. But they also noted the 18% side-effects figure. That had come from an observational study that said statin-related events were documented for 17.4% of adults taking the drugs at Brigham and Women’s Hospital and Massachusetts General Hospital in Boston.

But in an editorial published today, Godlee says the side-effects statement was a mistake. It is being withdrawn from the article and from an opinion piece, published at the same time, that also used the figure. It was based on a “misreading” of the observational study, says the editorial (although the conclusion on the lack of benefits stands).

“The true incidence of adverse events from use of statins in people at low risk of cardiovascular disease continues to be disputed. Data compiled by the CTT Collaboration show that rates of adverse effects are similar in the active and the placebo arms in trials of statins,” writes Godlee. She adds, “This editorial aims to alert readers, the media, and the public to the withdrawal of these statements so that patients who could benefit from statins are not wrongly deterred from starting or continuing treatment because of exaggerated concerns over side effects.”

Godlee says that her journal was alerted to the error by Rory Collins, an epidemiologist at the University of Oxford, UK, and head of the team whose data Abramson re-analysed. Collins wishes both articles to be withdrawn, but the BMJ says this is not necessary, as the error was not the main thrust of the articles. The journal has convened an independent panel to look into whether the articles should be retracted.

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.”

 

 

UK politicians wade into pharma mega-deal

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Pharmaceutical giant Pfizer has attempted to reassure UK politicians over its attempts to buy AstraZeneca, as political parties traded blows over the potential merger.

AstraZeneca today rejected an improved offer of approximately £50 (US$84) per AstraZeneca share from New York-based Pfizer, which would have valued the London-based company at around £63 billion ($106 billion).

As well as releasing this new bid, Pfizer today took the unusual move of sending a public letter to Prime Minister David Cameron, after a number of commentators expressed fears that a merger could devastate the UK research ecosystem if the resulting company slashed research and development (R&D). In 2011 Pfizer shocked many observers in the United Kingdom when it closed the Sandwich research park as part of global cuts to research.

“We recognize that our approach [to buy AstraZeneca] may create uncertainty for the UK Government and scientific community,” says the letter. It also commits Pfizer to setting its corporate and tax headquarters in the United Kingdom, completing AstraZeneca’s planned research site in Cambridge and employing at least 20% of the merged company’s R&D work force in the country.

On BBC radio this morning the government’s science minister sparred with his opposition number over the merger.

“We have been having very tough conversations with Pfizer and have made it clear to them that the British government attaches great importance to the R&D activities happening here in Britain and also manufacturing,” said science minister David Willetts. He added the government would expect Pfizer to commit to R&D and manufacturing in the United Kingdom if there were a merger but that this would ultimately be a decision for the AstraZeneca stakeholders.

But his counterpart in the opposition, shadow science minister Chuka Umunna, said that Pfizer has a “very poor” record on previous purchases, which had led to “deep cuts” in research facilities, and that the government was not doing enough to protect UK research.

Acid-bath stem-cell scientist apologizes and appeals

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Posted on behalf of David Cyranoski

Haruko Obokata, the Japanese scientist at the centre of a controversy over studies purporting to turn mature cells to stem cells simply by bathing them in acid or subjecting them to mechanical stress, today apologized for her errors in the work.

Kicking off a press conference in Osaka amid a storm of snapping cameras and flanked by two lawyers, Obokata blamed her immaturity and her lack of awareness of research protocols for the errors that were found in her two high-profile papers on the studies, published in Nature in January (Note: Nature’s news and comment teams are editorially independent of its research editorial team). These included the use of a duplicated image.

She took full responsibility for the errors, and apologized to her co-authors for the mess she got them into. Obokata, in her first public statement in more than two months, also apologized to her institute, the RIKEN Center for Developmental Biology, for the embarrassing press the whole ordeal had brought. In addition, she sought forgiveness from the RIKEN committee whose report earlier this month found her guilty of scientific misconduct. She had attacked the report at the time.

Obokata held the press conference for two reasons: to apologize for the errors and to make the case that her research was still valid and that the inaccuracies in the papers were not deliberate. Yesterday, she submitted a formal appeal to RIKEN that their committee retract its misconduct findings. She insisted that the “stimulus-triggered activation pluripotency” or STAP phenomenon, as it has been dubbed, exists. RIKEN has 50 days to respond to her appeal.

In the STAP work, lead author Obokata, along with Japanese and US colleagues, described stunning experiments in which she reprogrammed mature mouse cells to an embryonic state merely by stressing them. But the two papers soon fell under suspicion and last month a RIKEN-appointed investigative committee found in a preliminary report that they contained numerous errors. In a further report on 1 April, the committee announced that two of the errors constituted scientific misconduct. On the same day, Obokata responded aggressively, with a written statement expressing “shock and anger” at conclusions she said had been reached without giving her a chance to explain herself. Today, her tone was very different: pleading for forgiveness and showering apologies. But she maintained that her findings hold true.

Obokata insisted that the two problems which led to the misconduct findings — the duplicated image and the swapping of a diagram of an electrophoresis gel — were only errors. She said she had not been given enough time to explain her side to the committee.

After her five plus minutes of introductory remarks, her lawyer gave a 20-minute presentation to make the case that neither problem added up to misconduct. Defining fraud as fabrication, he countered that in both cases Obokata had the original data that should have been used but merely added the wrong data by mistake. For the more damning finding — an image of teratomas that had appeared in her doctoral dissertation and then again in the recent papers — the committee had found that she had changed a caption, which made it look intentional. The lawyer however traced the image back to a slide, part of a presentation that Obokata had continually updated and reused, until its origin became obscured. (Later, in one of her many apologies, she said, “If I had gone back to carefully check the original data, there wouldn’t have been this problem.”)

After the lawyer’s talk, Obokata responded to journalists’ questions for more than 2 hours. In response to suspicions based on the fact that she only handed two laboratory notebooks over to the committee looking into her research, she said she had four or five more that the committee hadn’t requested. She denied that she ever agreed to retract the papers. She also corrected reports that she had asked to retract her PhD dissertation, saying that she merely sought advice on how to proceed. Her dissertation is under investigation at Waseda University, where she studied for her doctorate.

Obokata also denied the possibility that the STAP cells had resulted from contamination from embryonic stem cells, saying that she had not allowed embryonic cells in the same laboratory and that she had carried out tests which precluded that possibility.

She said that she had created STAP cells more than 200 times, adding that she knows someone who has independently achieved it but refused to give the name (citing privacy). She believes that a RIKEN group trying to demonstrate STAP cells will help her. She has not, she said, been asked to participate in those efforts. She added that she would consider doing a public replication experiment but that it was not up to her whether she could.

Two hours into the questioning, her lawyer cut off journalists, citing concern for Obokata’s frail emotional state, and said she had to return to the hospital where she has been staying. She bowed, apologized, then bowed again and left. The press cameras contined to snap away.

 

New cholesterol drugs make strides in clinical trials

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The excitement around PCSK9 — a promising protein target for cholesterol-lowering therapies — seems to be justified. This week, at the American College of Cardiology’s annual meeting in Washington DC, several pharmaceutical companies presented data from advanced clinical trials showing that monoclonal antibodies that target and degrade PCSK9 are effective at treating patients with high cholesterol, especially when combined with statins such as Lipitor.

PCSK9, which circulates in the blood, prevents the liver from importing and processing low-density lipoprotein (LDL), or ‘bad’ cholesterol. People with genetic mutations that lower levels of PCSK9 in the blood also have lower cholesterol levels. (A 2013 feature story in Nature details how PCSK9 was discovered through the Human Genome Project.)

In one of five advanced-stage clinical trials it presented this week, Amgen, based in Thousand Oaks, California, showed that its new drug, evolocumab, lowered cholesterol by 57%, on average, in 901 patients who took the drug for a year. The company is in the process of enrolling more than 30,000 people in further clinical trials.

Evolocumab has two close competitors.  One is alirocumab, made by Sanofi, based in Bridgewater, New Jersey, and Regeneron, based in Tarrytown, New York. Alirocumab lowered cholesterol by nearly 50% compared to a placebo, and by 75% when combined with a statin. Finally, New York City-based Pfizer showed that its drug bococizumab lowers cholesterol by up to 67% when combined with a statin.

Jay Edelberg, who heads PCSK9 development at Sanofi, says that monoclonal antibody treatments could be especially useful for people who cannot take statin drugs or who have a genetic predisposition to high cholesterol.

All four companies now have larger trials underway, in which they will continue testing for adverse effects and determine whether the lowered cholesterol actually decreases a patient’s risk of heart disease. If all goes well, Amgen plans to file for regulatory approval for evolocumab later this year, and Sanofi and Regeneron plan to file in 2015.

 

 

WHO doubles estimates of air pollution’s health toll

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The World Health Organization has singled out air pollution as the number one environmental health risk in the world. In 2012, more than 7 million people worldwide died as result of exposure to either indoor or outdoor air pollution — one of every eight deaths — the Geneva-based organization warns in a report released today.

The death toll, calculated on the basis of a global analysis of pollution-related health risks and mortality across all ages in rural and urban areas, more than double previous estimates.

Low- and middle-income countries in the WHO’s South-East Asia and Western Pacific Regions — the latter including China, the Philippines and Vietnam — bear the main share of the burden. In 2012, around 3.3 million deaths in those regions were related to indoor air pollution and a further 2.6 million to outdoor air pollution, according to the WHO report.

Heart disease, stroke, lung cancer and acute respiratory infections in children are among the most common diseases linked to air pollution, it says.

Leaky coal and wood stoves are the main cause for widespread indoor air pollution in poor countries. Women and children who stay at home and breathe in smoke and soot are most at risk, says Flavia Bustreo, the WHO’s assistant director-general for family, women and children’s health.

“Cleaning up the air we breathe prevents non-communicable diseases as well as reduces disease risks among women and vulnerable groups, including children and the elderly,” she says.

The WHO says that it will later this year release indoor air quality guidelines on household fuel combustion. It will also publish new country-by-country data on exposure to outdoor and indoor air pollution and updated air quality measurements from 1,600 cities across the globe.

Acid-bath stem-cell team releases tip sheet

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A group of Japanese researchers whose revolutionary method to  produce stem cells simply drew questions from other biologists has published more details of their protocol.

The authors, who developed an ‘acid-bath’ technique that others have so far been unable to reproduce, released technical tips with a press statement today and published them on Nature Protocol Exchange. The document is entitled ‘Essential technical tips for STAP cell conversion culture from somatic cells’.

In it, Haruko Obokata, Hitoshi Niwa and Yoshiki Sasai, all of the RIKEN Centre for Developmental Biology in Kobe, say that despite its “seeming simplicity”, the method requires special care. But it is “absolutely reproducible”, Niwa told Nature News.

The controversy began at the end of January when Obokata and colleagues released two papers in Nature detailing how stress — in the form of low pH or physical pressure — could trigger the reprogramming of a mouse’s cells into an embryonic state, a process they called stimulus-triggered acquisition of pluripotency (STAP).

Cells reprogrammed into this state are ideal for studying the development of disease or the effectiveness of drugs, and could also be transplanted to regenerate failing organs. Making another type of pluripotent stem cell, called induced pluripotent stem (iPS) cells, requires a complex recipe of chemical or genetic factors. Obokata’s simple technique made headlines around the world.

But after the papers were published, they came under attack for a number of reasons, including the presence of duplicated images, an apparently plagiarized passage and the abnormal presentation of certain data. This led some commenters to question the validity of the results.

Something that would resolve the controversy would be the replication of the results by another group, but so far there have only been reports of failed attempts.

Despite a media frenzy, especially in Japan, with headlines even suggesting the results are fraudulent, the authors have stood by the work. Today Niwa told Nature News that members of the team besides Obokata have replicated the bulk of the work and that others outside the laboratory have succeeded in the first crucial step, inducing Oct3/4 expression after the acid treatment.

But the authors admit that the procedure is more complicated than originally advertised, leading to the publication of the tips.

The 10-page document states: “Despite its seeming simplicity, this procedure requires special care in cell handling and culture conditions, as well as in the choice of starting cell population.” The authors also point to the importance of bringing the cells gradually to the brink of death — which kills some 80% of them after 2–3 days — to reach the “optimal level of sub-lethal stress”.

The tips break down the process into three sections: collection of tissue and treatment with low-pH needed to produce STAP cells; preparing the culture needed to convert STAP cells to STAP stem cells, which behave like iPS cells or embryonic stem cells; and preparing the culture needed to turn STAP cells into “FI cells”, which can form placenta.

The document includes 28 “important” tips, which note the necessity of starting with primary cells (as opposed to cultured cells); that mice less than a week old, especially male mice, gave better results; the recommendation of using non-adhesive plates, which allow cell mobility and cluster formation; the importance of getting the cell density right in culture; the recommendation of using mice of a specific genetic lineage and many other detailed hints for using the proper culture conditions.

Martin Pera, a stem-cell researcher at the University of Melbourne in Australia, says: “The details provided in Nature Protocol Exchange will undoubtedly be helpful to those trying to repeat these findings.” But Pera, who has not tried to make STAP cells, adds: “The additional information does not seem to me to reveal any key procedural detail without which it would be impossible to duplicate the work. It appears instead to reinforce and emphasise some aspects of the technique that were disclosed originally.”

Those who are trying to replicate the method are intrigued by the publication of the tips. Jacob Hanna, at the Weizmann Institute of Science in Rehoboth, Israel, has made 10 batches of cells in an as-yet-unsuccessful effort to make STAP cells. He looks forward to trying some of the tips on culture conditions. “Some protocols can indeed be tricky and finicky and I commend the authors on making the effort to reach out to the scientific community,” he says. But he questions how the more complicated protocol would apply to another method of producing STAP cells advertised in the original article — putting pressure on the cell membranes. “I find that hard to imagine as a very complicated manipulation,” he says.

Qi Zhou, of the Institute of Zoology in Beijing, also appreciates the authors sharing all the details, as “some were overlooked” in his efforts to make STAP cells. The restrictions on the origin of the cell type to specific stage and gender “raise very interesting questions which may help to explain the underlying mechanism of STAP”, he says.

Niwa says that the original team is working on a “full protocol” that will make it easier to make STAP cells, but that won’t be available for at least a month. “We are not sure when it will happen because we are now trying to improve some point to enhance the reproducibility,” he says.