Contamination created controversial ‘acid-induced’ stem cells

Stem cells that were claimed to be created simply by exposing ordinary cells to stress were probably derived from embryonic stem cells, according to the latest investigation into an ongoing scientific scandal. How that contamination occurred, however, remains an open question.

The investigation was instigated by RIKEN, the Japanese research institution where the original claims were made, and carried out by a committee composed of seven outsiders.

The committee analyzed DNA samples and laboratory records from two teams behind the original papers describing STAP (‘stimulus-triggered acquisition of pluripotency’) cells.  Those papers — published in Nature but later retracted  — were once heralded as describing a shortcut to producing stem cells: rather than expressing specific genes or carefully transplanting a nucleus from one cell to another, researchers could, it seemed, create stem cells by exposing them to stress, including bathing the cells in acid.

The latest investigation suggests that the STAP findings were merely the result of contamination by embryonic stem cells. Investigators found signs of three separate embryonic stem cell lines. They noted that it is difficult to imagine how contamination by three distinct lines could be accidental, but that they could also not be certain that it was intentional. 

“We cannot, therefore, conclude that there was research misconduct in this instance,” the committee wrote. It did, however, find evidence that lead investigator Haruko Obokata, formerly of the RIKEN Center for Developmental Biology in Kobe, had fabricated data for two figures in the original STAP publications.

The committee’s report, released on 26 December, is the latest in a series of damning revelations about the STAP cells originally described in two Nature papers in January 2014. The approach quickly came under scrutiny as other researchers failed to reproduce its results, and as suspicions grew that images in the original papers had been manipulated. In March, another RIKEN investigation found Obokata guilty of scientific misconduct; in July, the STAP papers were retracted  and in August another co-author, Yoshiki Sasai, took his own life. Earlier this month, Obokata resigned her position at RIKEN.


US to lift ban on blood donations from gay men

The US Food and Drug Administration has announced plans to end a lifetime ban on blood donation for men who have sex with men that has been in place since 1983. The current ban covered all men who have had sex with men at any time since 1977, and was intended to prevent the spread of the HIV virus but was seen by gay-rights activists as discriminatory.

The new policy, revealed on 23 December, will allow gay and bisexual men who have abstained from sex for a year to donate blood. The move follows the recommendations of a US government advisory panel.

The United Kingdom lifted an analogous ban in 2011, also allowing donations by gay men who have abstained from sex for a year.

In a statement, Adaora Adimora, Chair of the HIV Medicines Association, supported the rule change, but said it fell short of some advocates’ hopes:

“[W]e are concerned that the new policy retains an unnecessary and unique exclusion of men who have sex with men from donating blood for one year. Requiring a one-year abstinence period for men who have sex with men, regardless of risk behavior is not grounded in science regarding transmission risks or supported by current diagnostics for detecting HIV infection and other blood-borne pathogens.”

In 2015, the FDA will issue the detailed draft policy, which will be open for public comment before being finalized.

Gates Foundation announces world’s strongest policy on open access research

The Bill and Melinda Gates Foundation has announced the world’s strongest policy in support of open research and open data. If strictly enforced, it would prevent Gates-funded researchers from publishing in well-known journals such as Nature and Science.

On 20 November, the medical charity, based in Seattle, Washington, announced that from January 2015, researchers it funds must make open their resulting papers and underlying data sets immediately upon publication — and must make that research available for commercial reuse. “We believe that published research resulting from our funding should be promptly and broadly disseminated,” the foundation states. It says it will pay the necessary publication fees (which often amount to thousands of dollars per article).

The foundation is allowing two years’ grace: until 2017, researchers may apply a 12-month delay before their articles and data are made free. At first glance, this suggests that authors may still — for now — publish in journals that do not offer immediate open-access (OA) publishing, such as Science and Nature. These journals permit researchers to archive their peer-reviewed manuscripts elsewhere online, usually after a delay of 6–12 months after publication.

Allowing 1 year’s delay makes the charity’s OA policy similar to those of other medical funders, such as the UK Wellcome Trust or the US National Institutes of Health (NIH). But the charity’s intention to close off this option by 2017 might put pressure on paywalled journals to create an OA publishing route.

However, the Gates Foundation’s policy has a second, more onerous twist that appears to put it directly in conflict with many non-OA journals now, rather than in 2017. Once made open, papers must be published under a licence that legally allows unrestricted reuse — including for commercial purposes. This might include ‘mining’ the text with computer software to draw conclusions and mix it with other work, distributing translations of the text or selling republished versions.  In the parlance of Creative Commons, a non-profit organization based in Mountain View, California, this is the CC-BY licence (where ‘BY’ indicates that credit must be given to the author of the original work).

This demand goes further than any other funding agency has dared. The Wellcome Trust, for example, demands a CC-BY licence when it is paying for a paper’s publication — but does not require it for the archived version of a manuscript published in a paywalled journal. Indeed, many researchers dislike the thought of allowing such liberal reuse of their work, surveys have suggested. But Gates Foundation spokeswoman Amy Enright says that “author-archived articles (even those made available after a 12-month delay) will need to be available after the 12-month period on terms and conditions equivalent to those in a CC-BY licence.”

Most non-OA publishers do not permit authors to apply a CC-BY licence to their archived, open, manuscripts. Nature, for example, states that openly archived manuscripts may not be reused for commercial purposes. So do the American Association for the Advancement of ScienceElsevier and Wiley and many other publishers (in relation to their non-OA journals).

“It’s a major change. It would be major if publishers that didn’t previously use CC-BY start to use it, even for the subset of authors funded by the Gates Foundation. It would be major if publishers that didn’t previously allow immediate or unembargoed OA start to allow it, again even for that subset of authors. And of course it would be major if some publishers refused to publish Gates-funded authors,” says Peter Suber, director of the Office for Scholarly Communication at Harvard University in Cambridge, Massachusetts.

“You could say that Gates-funded authors can’t publish in journals that refuse to use CC-BY. Or you could say that those journals can’t publish Gates-funded authors. It may look like a standoff but I think it’s the start of a negotiation,” Suber adds — noting that when the NIH’s policy was announced in 2008, many publishers did not want to accommodate all its terms, but now all do.

That said, the Gates Foundation does not leave as large a footprint in the research literature as the NIH. It funded only 2,802 research articles in 2012 and 2013, Enright notes; 30% of these were published in OA journals. (Much of the charity’s funding goes to development projects, rather than to research which will be published in journals.)

The Gates Foundation also is not clear on how it will enforce its mandate; many researchers are still resistant to the idea of open data, for instance. (And most OA mandates are not in fact strictly enforced; only recently have the NIH and the Wellcome Trust begun to crack down.) But Enright says that the charity will be tracking what happens and will write to non-compliant researchers if need be. “We believe that the foundation’s Open Access Policy is in alignment with current practice and trends in research funded in the public interest.  Hence, we expect that the policy will be readily understood, adopted and complied with by the researchers we fund,” she says.

Energy outlook sees continuing dominance of fossil fuels

Just as the United States and China agreed on a landmark deal to curb greenhouse-gas emissions, the world’s leading energy think tank says that demand for fossil fuels is likely to keep growing for at least another 20 years.



In its latest World Energy Outlook, released on 12 November, the Paris-based International Energy Agency (IEA) estimates that global consumption of primary energy — the energy contained in raw fossil fuels — will increase by 37% by 2040, driven mostly by growing demand in Asia, Africa, the Middle East and Latin America.

Crude-oil consumption is expected to rise from the current 90 million barrels a day to 104 million barrels a day, but demand for oil will plateau by 2040, according to IEA scenarios. Coal demand will already peak in the 2020s, thanks to efforts such as China’s to reduce air pollution and carbon emissions. But the demand for natural gas, the only fossil fuel that in the IEA’s scenarios is still growing after 2040, will rise by more than half, the report says.

The output from US shale projects, which has been booming — propelling the country to become the world’s largest producer of oil and gas — is expected to decline in the 2020s, the IEA says. Even so, there are sufficient untapped resources to meet the growth in consumption. And despite a recent slump in the prices of oil and gas, the IEA warns that rising tensions in parts of the Middle East and in Ukraine pose incalculable threats to global energy security.

“A well-supplied oil market in the short-term should not disguise the challenges that lie ahead, as the world is set to rely more heavily on a relatively small number of producing countries,” the IEA’s chief economist Fatih Birol said when the report was released in London. “The apparent breathing space provided by rising output in the Americas over the next decade provides little reassurance.”

Widespread safety concerns over the use of nuclear power mean that few countries — including China, India, Korea and Russia — are planning to increase their installed nuclear capacity. Nearly 200 of the 434 reactors that were operational at the end of 2013 are set to be retired in the period to 2040. Germany and other countries that decided after the Fukushima-Daiichi accident in 2011 to phase out nuclear power altogether are facing the challenge of addressing the resulting shortfall in electricity generation.

No country has as yet found a long-term solution to the problem of disposing of radioactive waste, the IEA notes.

The IEA reckons that renewable sources — mainly wind and solar — will provide nearly half of the global increase in power generation to 2040. By then, low-carbon sources, including nuclear, are expected to supply about a quarter of the global energy consumption.

However, the IEA  also predicts that between now and 2040 the world will add 1 trillion tonnes of carbon dioxide to the atmosphere — using up the budget that climate scientists say can give the world a reasonable chance to limit the rise in global average temperatures to 2˚C or less.

That calculation will sound cynical to more than half a billion people in sub-Saharan Africa — the regional focus of the report — who live without access to modern energy. Africa’s poorest suffer in fact the most extreme form of energy insecurity in the world, says the IEA.


Private rocket explodes on launch to space station

Flames engulfed the rocket seconds after lift-off.

Flames engulfed the rocket moments after lift-off.


An Orbital Sciences Antares rocket exploded seconds after its 6:22 p.m. lift-off from Wallops Island, Virginia, Tuesday on a mission to resupply the International Space Station. No one was hurt, but the rocket was apparently destroyed and there was “significant property damage”, according to mission control commentators on NASA television.

“We have lost the vehicle,” said controllers from the Johnson Space Center in Houston. “The [space station] crew has been informed of the accident.”

Orbital moved almost immediately into contingency mode, asking its engineers to retain all notes and photographs related to the launch. Fires could be seen burning across the launch pad. “Obviously we will need to instigate an accident investigation team,” the launch director said.

Orbital, of Dulles, Virginia, is one of two private companies flying cargo to the space station for NASA. Its competitor, SpaceX of Hawthorne, California, is aiming to eventually carry astronauts as well.

It was the third of eight scheduled missions for Orbital. Among the 2,300 kilograms of cargo on board were a spectrometer to measure meteors entering the atmosphere and a neck collar for astronauts to measure blood flow from the brain. The payload also included test hardware for a future private asteroid prospecting mission, as well as unspecified classified cryptography equipment.

Launch of a Russian Progress vehicle, scheduled for the morning of 29 October with more crew supplies, was not expected to be affected.


WHO plans for millions of doses of Ebola vaccine by 2015

Posted on behalf of Declan Butler.

The World Health Organization (WHO) announced plans on 24 October to produce millions of doses of two experimental Ebola vaccines by the end of 2015.

The Ebola virus has caused about 5,000 deaths in West Africa during the current epidemic.

The Ebola virus has caused about 5,000 deaths in West Africa during the current epidemic.


Hundreds of thousands of doses should be available to help affected countries before the end of June, the WHO said at the conclusion of a meeting in Geneva, Switzerland. Vaccine makers, high-level government representatives and regulatory and other bodies gathered to discuss the design and timing of planned clinical trials, as well as issues of supply and funding for mass vaccination programmes.

Phase I trials of two vaccine candidates have started, and as many as five other vaccines could begin testing by 2015, says Marie-Paul Kieny, WHO assistant director-general for health systems and innovation.

As of 19 October, Ebola had infected almost 10,000 people in Sierra Leone, Liberia and Guinea and killed around 5,000 of them, the WHO estimates. The true figures are probably higher, as many cases go unreported. With no end to the epidemic yet in sight, a working vaccine could be a game changer.

First clinical trials under way

The two vaccines whose production will be increased are already in early-stage testing in healthy volunteers. One is a chimpanzee adenovirus vaccine containing a surface Ebola protein (ChAd3), developed by the US National Institute of Allergy and Infectious Diseases and drug giant GlaxoSmithKline (GSK). It is being tested in the United States, the United Kingdom and Mali.

The other is a recombinant vesicular stomatitis virus (rVSV) vaccine, developed by the Public Health Agency of Canada and licensed to NewLink Genetics in Ames, Iowa. It is being tested in the United States, with plans to start trials soon in Europe and Africa.

These phase I trials will assess the vaccines’ safety and whether they elicit levels of immune response that have been shown to confer protection in non-human primates. The trials will also assess the dose needed to generate sufficient immune response, which in turn helps to determine how quickly manufacturers can produce doses.

A third candidate is a two-vaccine regimen: one developed by US pharmaceutical company Johnson and Johnson and the US National Institute of Allergy and Infectious Diseases, and another by Bavarian Nordic, a biotechnology company based in Denmark. It will begin phase I testing in the United States and Europe in January. Johnson and Johnson announced on 22 October that it would spend up to US$200 million to fast track the vaccine’s development; it plans to produce more than 1 million doses in 2015, with 250,000 available by May.

Advanced testing

The first phase II and III trials, to test efficacy as well as safety, are set to start in Liberia in December and in Sierra Leone in January. The current plan is to test both the GSK and NewLink vaccines simultaneously, but that could change depending on the results of the ongoing phase I trials. Data from the phase II and III tests are expected by April, Kieny says.

The ‘three-arm’ Liberia trial would test and compare the safety and effectiveness of the two vaccines against each other and a placebo. Each vaccine would be tested on 10,000 subjects, with an equal number of subjects given placebo. This allows researchers to obtain quick, reliable data on how well the vaccines work.

A ‘stepped-wedge’ randomized trial in Sierra Leone would give subjects vaccine sequentially, with no group given a placebo. This is useful for testing products that are expected to benefit patients, and products that are in short supply.

No trial design has yet been fixed for Guinea, where a lack of infrastructure has precluded early testing. If the Liberia and Sierra Leone trials show that the vaccines works and is safe, subsequent trials in Guinea would be used to answer follow-up questions.

Ethical and practical considerations

The Sierra Leone trial will enrol at least 8,000 health-care workers, and other frontline responders, such as ambulance drivers and burial workers. The Liberia trial might include health-care workers, but these would not be the primary study population, Kieny says.

Any decision to give a placebo to health-care and other frontline workers will be controversial; many consider it to be unethical, given these individuals’ work caring for Ebola patients, and the risks that they face in doing so.

Mass vaccinations are usually only carried out after years of trials to accumulate full safety and efficacy data. The proposed timeline for Ebola vaccine development is therefore unprecedented.

If existing public-health interventions to control Ebola outbreaks begin to slow the epidemic, the need for mass vaccination will lessen, Kieny says. But if the epidemic continues to expand, the WHO could consider expanding vaccination programmes.

In the meantime, the WHO and its partners are considering how best to engage with communities to prepare for vaccination programmes. Another issue is simply determining how to keep vaccine at –80 degrees Celsius, the temperature needed to maintain its efficacy. This will require specialized refrigerators and the establishment of cold supply chains to affected areas.

Also to be determined is who will pay for mass vaccination. Kieny says simply that “money will not be an issue”. Aid groups and governments have begun to pledge support for such efforts. Médecins Sans Frontières (MSF, also known as Doctors Without Borders) has said that it will create a fund for Ebola vaccination, and the European Union has committed €200 million (US$255 million). The Gavi vaccine alliance, the main sponsor of routine vaccinations in low-income countries, is also looking at how it could bring its vast resources and experience to the table. It will put a plan to its board in December as to what role it could have in any Ebola mass vaccination.

Western Australia abandons shark cull


Western Australia Premier Colin Barnett

Government of Western Australia

The state of Western Australia is abandoning a controversial shark-culling programme, but has also gained the right to deploy deadly baited lines for animals that pose an “imminent threat”.

The programme, run by the state government off several Western Australian beaches, had been heavily criticized by scientists when it was announced in 2013. It was due to run until 2017, and had caught at least 170 sharks using hooks suspended from drums moored to the sea floor.

In September the state’s own Environmental Protection Agency halted it. State Premier Colin Barnett then applied to the national government for permission to resume it, but today he announced that his government had ended that effort. “We have withdrawn the application after reaching agreement with the Commonwealth which enables us to take immediate action when there is an imminent threat,” said Barnett.

Under an agreement with the national government, Western Australia will be able to kill sharks in future to deal with a shark that has attacked or with one that it thinks poses a threat. Protocols for how this would happen are now in development.

This apparent concession from the national government has drawn some concern from those celebrating the end of the cull.

“I remain concerned that drum lines could be used in some instances as part of emergency measures and particularly that this could occur without Federal approval,” said Rachel Siewert, the marine spokeswoman for the Australian Greens, in a statement.

The Western Australia cull is also drawing renewed attention to the longstanding cull in Queensland, which continues unabated.

Fundamental overhaul of China’s competitive funding

On 20 October, the Chinese government announced the passage of a reform plan that will fundamentally reshape research in the country.

By 2017, the main competitive government funding initiatives will be eliminated. This includes the ‘863’ and ‘973’ programmes, two channels for large grants that have been at the heart of modern China’s development of science and technology infrastructure since being established in 1986 and 1997, respectively.

Xi Jinping, General Secretary of the Communist Party of China, is behind reforms to overhaul research in the country.

Xi Jinping, General Secretary of the Communist Party of China, is behind reforms to overhaul research in the country.

By Antilong (Own work) [CC-BY-SA-3.0], via Wikimedia Commons

The government announcement noted that wastefulness and fragmented management has led to overlaps and inefficient use of funds for science and technology, and the need for a unified platform for distributing grants. As new funding programmes have been added over the years, competitive funding has become divided among some 100 competitive schemes overseen by about 30 different governmental departments.

Although efforts to reorganize science in China are already underway,  the latest reform will be comprehensive. Science and technology spending by the central government was 77.4 billion yuan renminbi (US$12.6 billion) in 2006 but jumped to 236 billion yuan renminbi in 2013, 11.6% of the central government’s direct public expenditure. Some 60% of this is competitive funding, and subject to change under under the new reforms. To maintain stability, the overhaul will not affect the remaining 40%, which covers operation costs for research institutes and key state laboratories.

The new plan, jointly drafted by the ministries of science and technology and the ministry of finance, will reorganize competitive funding into five new channels: the National Natural Science Foundation (which currently distributes many of the small-scale competitive grants); national science and technology major projects; key national research and development programmes; a special fund to guide technological innovation; and special projects for developing human resources and infrastructure. These five will be managed under a new science and technology agency that will unify planning and assessment of scientific projects.