Full text of ' THIS WEEK l/IW EDITORIALS HUE SAYS? Colour firmly in the confused eye of the beholder p.6 WORLD VIEW China seeks I global leadership in GM food p.7 PLANTS Gene disrupter keeps the potato pests awayp.9 Gone fishing An investigation into the funding sources of climate scientists who have testified to the US Congress makes demands that have the potential to infringe on academic freedom. P erhaps it was to be expected.

Just days after documents surfaced that raised conflict-of-interest questions about the funding sources of noted climate sceptic Willie Soon, a member in the US House of Representatives entered the fray. On 24 February, Raul Grijalva, the leading Democrat on the House Committee on Natu- ral Resources, released letters that he had sent to seven universities demanding information on the funding sources of seven other scien- tists whose views he does not appreciate. Grijalva was right when he wrote in the letters that conflicts of interest “should be clear to stake- holders”, but his investigation sends all the wrong messages. Somewhere behind Grijalva’s motives there is a legitimate point. Scientists have a responsibility to disclose their funding sources and any other ties that could be perceived as conflicts of interest when they publish their work. Institutions, including the Harvard- Smithsonian Center for Astrophysics (CfA) in Cambridge, Massachusetts, where Soon works, must establish policies that lay out the rules for their researchers. Scientific journals must also ask authors to declare pos- sible conflicts.

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These disclosures should apply to funding from indus- try and from foundations, regardless of which way they lean, as well as from environmental groups. Where there is evidence that these standards are not being met, there is certainly scope to investigate why. As a result of documents obtained through a US Freedom of Informa- tion Act and released last month by environmentalists, the CfA is now reviewing Soon’s case and its own policies (see Nature 2015). This is as it should be, but Grijalva’s inquiry is a fishing expedition that seems to have been crafted for publicity rather than clarity.

Among his targets are a few long-time climate sceptics, such as Richard Lindzen in Cambridge. Also on the list are policy researcher Roger Pielke Jr at the University of Colorado Boulder, whose sin has been to question political convention on climate issues, and Judith Curry, a climate scientist at the Georgia Institute of Technology in Atlanta who has engaged with climate sceptics. All of the researchers have testified before Congress, and Grijalva says that his goal is to maintain public confidence in public institutions by ensuring that public policies are not improperly influenced by outside money. Unfortunately, he laments, congressional disclosure require- ments did not compel researchers to report their sources of funding, and “we need to fill in those gaps”. His letters are addressed to the presidents of the researchers’ universities and request information about financial disclosure policies, sources of external funding and any formal disclo- sures of such funding. They also ask for all drafts of public testimony that the researchers “helped prepare for others” and any communications about the preparation of testimony.

Not only does this investigation shine a high-profile light on research- ers before the evidence to judge them has even been gathered, but it goes well beyond questions about funding and disclosure by seeking early testimony drafts and personal correspondence. (Grijalva admitted earlier this week that this was an “overreach”, although he is letting his 5 MARCH 2015 VOL 519 NATURE 5 © 2015 Macmillan Publishers Limited.

All rights reserved “Politicians are singling out researchers with whom they disagree. ” requests stand for now.) A spokesman for Grijalva and the committee’s Democratic minority sought to distinguish between this investigation and a 2005 episode in which former chairman of the House Energy & Commerce Committee Joe Barton (Repub- lican, Texas) requested personal communi- cations and scientific data on palaeoclimate research from scientists including Michael Mann, now at Pennsylvania State University in University Park. Grijalva is not seeking scientific data, but there is a reason for the comparison. In both cases, politicians are singling out researchers with whom they disagree and are seeking access to private deliberations that should be protected in the name of academic freedom. Scientists must view their funding sources as public information that is always subject to scrutiny, and act accordingly. But when politicians seek to probe beyond possible sources of external influence on pub- lished work and attempt to expose internal discussions that they find inconvenient, that sends a chilling message to all academics and to the wider public.

■ Fatal fallout The Ebola epidemic has had a dire effect on the health prospects of pregnant women. T he late stages of pregnancy are a difficult time for most women, but try to imagine what it must be like right now for would-be new mothers in rural areas of Sierra Leone, Guinea or Liberia. Their eight or nine months of pregnancy have already been over- shadowed by the ravages of the Ebola outbreak.

Now, when they start to feel abdominal cramps, they are faced with an impossible choice. Before the epidemic, health educators urged pregnant women with complications to report to clinics. But the nearest clinic is typically a journey of a day or more away — and stories abound of friends and relatives who went to the hospital, only to be told that they had Ebola and never come home.

Pregnant women who do brave the journey are often denied care. Some end up delivering their babies alone on floors or in the backs of ambulances. What would you do — would you make the journey? Now put yourself in the place of the hospital nurse greeting a heavily pregnant woman who arrives at a triage department, weary from her journey, and complaining of abdominal pain.

Such pain is, after all, a classic symptom of Ebola, and although the numbers of cases are easing, you have seen colleagues and friends help pregnant women with Ebola, THIS WEEK EDITORIALS only to contract the virus and die. The womans pain worsens and she goes into labour.

Would you help? Or, to protect yourself, would you leave her squirming on the floor to deliver the baby herself? As we explore in a News Feature on page 24, women and health workers in West Africa are facing decisions like these every day. It helps to explain how, as new infections of Ebola are finally being brought under control and the world s attention moves on, the out- breaks devastating impact on maternal health will linger for years.

Pregnant women are uniquely vulnerable to the effects of Ebola, and it is extremely difficult to distinguish the diseases symptoms from routine pregnancy complications. And those who care for these women take their lives in their hands: pregnancy and childbirth necessarily expose carers to potentially infectious bodily fluids. As a result, many doctors, nurses and clinics have refused to treat any pregnant woman who pre- sents with symptoms that could mark her as having Ebola. The United Nations Population Fund (UNFPA) has estimated that the maternal mortality rate — the annual number of maternal deaths per 100,000 live births — may double as a result. And this is happening in countries that already had among the worst maternal-health records in the world. Some health workers have been brave enough to continue caring for pregnant women during the Ebola epidemic.

These include doc- tors with the medical-aid group Medecins Sans Frontieres (Doctors Without Borders) who have devised innovative ways to treat these women and have opened clinics specifically to care for these most vulnerable patients. Samuel Batty and Amadu Jawara, two Sierra Leonean community health workers, have also stepped up.

Both were assigned to work at a hospital in Freetown. When many nurses and doctors abandoned their posts, Batty and Jawara did not. In November, Batty and Jawara assisted a pregnant woman with a fever. They gave her medication and her fever improved. Assuming that she had malaria, Batty examined her using no special Ebola pre- cautions. It was a fatal mistake.

Soon after, Batty himself died of the disease. Even after seeing his friend die, Jawara has continued to care for patients, knowing that they have nowhere else to turn.

He estimates that he has performed 100 Caesarean sections. Community health workers would not usually perform such a procedure. Both Batty and Jawara were trained in surgical skills through a programme run by the Norwegian non-governmental organization CapaCare in conjunction with the Sierra Leonean health ministry. The programme exemplifies an approach called surgical task- shifting, which attempts to redress the dearth of medical personnel in countries such as Sierra Leone by training health workers to give lifesaving care that might otherwise be unavailable to patients in under- resourced areas. CapaCare estimates that, by August 2014, approximately half the surgical procedures performed by its stu- dents were emergency obstetric procedures. There is debate over the ethics of task- shifting: some worry that it risks exposing patients to substandard care.

But the epidemic shows that the people trained by CapaCare are extraordinarily committed to their patients. In this setting, many people faced a choice of being cared for by Jawara, Batty and their counterparts or receiving no care at all. Sierra Leone had only seven obstetricians before the outbreak began. The UNFPA is seeking US$56 million to fund a new initiative to reopen health services for pregnant women and to recruit more than 500 midwives, doctors and health workers across the outbreak region. International donors should support this initiative. Training more doctors and finding ways to incentivize them to stay in West Africa are priorities to help the region replace health workers who have lost their lives fighting the epidemic, and task-shifting has proved that it can be part of the solution.

The Capa- Care programme is currently on hold as a result of the deaths of Batty and another trainee. Restarting medical programmes, including ones such as this, are crucial as the region fights to end the outbreak and begin the long recovery process. ■ “Pregnant women are uniquely vulnerable to the effects of Ebola. ” Hues and cry A blue dress divided the Internet — and put the science of visual perception in the spotlight.

T he influence on science and the arts of Johann Wolfgang von Goethe — poet, playwright, novelist, proto-scientist, philosopher and general all-round egghead — is profound. His views about the physiological nature of colours, however, have never really caught on, in part because he proposed that colours are more an invention of the mind than a physical reality. One thing, however, rings true: the appearance of objects is not objective, but a conversation between the observer and observed. Neuroscientists have long recognized that the perception of colour and shade depends strongly on context. Illusions exist, for example, in which one can be utterly convinced that black is white, depending on the surrounding patterns or the conditions in which an object is lit. But it is also true that all other things being equal, the perception of colour differs between people.

One editor of this journal, for example, once owned a car that was, in his opinion, quite clearly green. It remained green in all conceivable circumstances of context, shade and illumination other than complete darkness. Except, however, that everyone else was equally convinced that it was blue — including the vehicle-licensing authority. The car was not only blue — it was officially blue. Last week, the Internet was deluged with strongly held opinion about colour, specifically of a dress.

The dress was advertised as being blue and black. But if illuminated in a certain way, the dress appeared white and gold. People were absolutely convinced of its colour combination, one way or the other. The web exploded with chromatic debate after various celebrities bruited their opinions on Twitter.

A straw poll of Natures editors (including the owner of the blue car) was roughly split down the middle, and convictions were strong — one way or the other. The explanation for the illusion lies in the colour of the light in which the dress was photographed. The brains of people who read the overall ambience as too blue will overcompensate, seeing the dress as white and gold. Others, whose visual systems read that the lighting was not blue enough, saw the dress as blue and black. Wired magazine hosted a full discussion on the effect (see go.nature. Com/uqf7bo), and the consternation in that publications office seemed to reflect the brouhaha that briefly reigned in the otherwise serene halls of Nature. (The wheels of this international weekly journal of science briefly ground to a halt as so: “I can’t read any more manu- scripts until I find out WHY?!”) On being told of the illusion, some people — but not all — could just about force themselves to see the dress as black and blue rather than white and gold.

The picture is a clear demonstration that colour percep- tion varies between individuals, and according to the conditions of illu- mination. Such perception is distinct from the genetic conditions that predispose people to the various syndromes known as colour blindness. Had the ghost of Goethe been watching ‘dressgate’, he might have allowed himself a rueful smile, given the brickbats thrown in his direction by his scientific critics even in his own ONATURE.COM time, who, he said, “forgot that science arose To comment online, from poetry, and did not see that when times click on Editorials at: change the two can meet again on a higher level go.nature.com/xhunqv as friends.” ■ 6 NATURE VOL 519 5 MARCH 2015 © 2015 Macmillan Publishers Limited. All rights reserved A personal take on events China’s scientists must engage the public on GM The country ’s shifting stance on genetic modification for crops needs the support of researchers to persuade a sceptical public, says Qiang Wang.

C hina is about to get serious on the use of genetic modification (GM). After years of uncertainty, funding cuts and public argu- ments, the country’s central government has issued a clear edict: China needs GM, and it will work to become a world leader in the development and application of the technology The intent is signalled by the government’s first policy document of the year. Issued on 1 February, the states No. 1 Central Document pledges more government support for research on GM techniques, especially for crops. China has expressed similar enthusiasm for GM technology before, and then backed off in the face of public protest. The policy document shows that the Chinese government does not want that to happen again.

The document highlights the need for com- prehensive studies to make sure that the technology is safe to use, and it also stresses that Chinese scientists must do more to convince a sceptical public of its benefits. The new responsibility placed on Chinese researchers to communicate with the public is a significant and positive step forward. It could help to counter the widespread and irrational fear in China that GM food is unsafe to eat.

A 2010 online poll of nearly 50,000 Internet users conducted by the news portal China Daily found that 84% would not choose GM food for safety reasons. Irrational opinions have some- times been so strong that scientists have been intimidated and shied away from speaking out. They fear the ‘soft violence of violent language’ that is too often directed at researchers who simply advocate the commercialization of GM technology.

China cannot afford to turn its back on GM. Policy-makers are right to include the technol- ogy in a new agricultural model for the country. To be self-sufficient, China must grow food for nearly one-fifth of the world’s population, with access to just 6% of the world’s fresh water and 7% of the world’s arable land.

In recent decades, China has performed heroics and pro- duced more and more grain — nearly doubling production between 1978 and 2013. But at what cost? The increase was driven by a sixfold rise in the use of chemical fertilizers, which pollute the land and water. Despite China’s reputation as a global factory, national reports identify agriculture, not industry, as the biggest source of pollution.

GM technology has the potential to produce more food with less pollution. Without it, China seems likely to become more dependent on imports to feed its people.

China imported a record 90 million tonnes of grain last year; cereal imports were up one-third on 20 1 3. O NATURE.COM Chinese policy-makers recognize the appeal Discuss this article of GM technology, but must address hostile online at: public opinion.

Official announcements on the go. Nature.com/o1zqn2 subject in 2014 even neglected to use the term, preferring instead the euphemism ‘molecular breeding’.

This might seem surprising given the Chinese government’s intolerance of dissent on some issues. But GM technology is seen as a less politically controversial topic, and one with more flexibility for public opinion to steer policy. As a result, China’s GM- crop -planting areas have declined since the late 1990s. Brazil and India now grow more GM crops than China.

Funding has also been cut: money for major GM-seed cultivation programmes was cut to 400 million yuan (US$63 million) in 2013, down from 2 billion yuan in 2010. Although China imports substantial amounts of GM products — maize (corn) and soya bean among them — it grows only cotton and papaya commercially. Cultivation of GM staple food crops, includ- ing rice, is banned, despite the government declaring in 2009 that two GM rice varieties were safe to grow. The new central document does not introduce specific policies or commitments to boost GM cultivation. These are likely to come later, from specific government agencies. But the decree is an important and influential signal of the state’s intentions.

Similar documents issued in the early 1980s, for example, accelerated land reforms, and catalysed the dismantling of Mao Zedong’s col- lective ownership of farms. This is widely seen as the start of broader changes in Chinese society, from a planned to a market-based economy. China needs a similar shift in its attitudes to GM. Despite their enthusiasm for GM technol- ogy, and their awareness of its importance for domestic agriculture and food production, the Chinese authorities have so far failed to weigh in on the very public debate over its safety. But it now looks as though that will change. Most scientists in China work directly or indirectly for the govern- ment. Traditionally, these researchers have not been given, or been encouraged to take on, any broader social duties or responsibilities.

The latest step could see Chinese scientists talking to the public about GM, as part of a wider effort to overturn scepticism and hostility. The popularity of social-media sites such as WeChat, which has around 400 million registered users in China, and Weibo (the Chinese version of Twitter) gives researchers a new way to enter into genu- ine and respectful dialogue over the true risks and benefits of GM. If China is to make good on its intentions to boost its GM efforts, then more scientists speaking up is a good place to start. ■ Qiang Wang is conjoint professor at the Xinjiang Institute of Ecology and Geography of the Chinese Academy of Sciences in Urumqi, China, e-mail: qiangwang7@outlook.com GM TECHNOLOGY HAS THE POTENTIAL TO PRODUCE MORE FOOD WITH LESS P0LL0TI0N.

5 MARCH 2015 VOL 519 NATURE 7 © 2015 Macmillan Publishers Limited. All rights reserved RESEARCH HIGHLIGHTS sret ZOOLOGY Eyelash length explained The optimal length for mammalian eyelashes is one-third of the eyes width, which helps to retain moisture and keep out dust. David Hu and his colleagues at the Georgia Institute of Technology in Atlanta measured the eyelash lengths of 22 species of mammals and found this ratio.

They tested mock- ups of a mammalian eye in a wind tunnel to see how airflow changed depending on eyelash length. Lashes that were shorter than one-third of eye width were not optimal at blocking air from blowing onto the ocular surface. However, longer lashes directed more airflow towards the eye, making it susceptible to drying out. Understanding how eyelashes function could lead to devices that protect optical sensors, the authors say. Interface (2015) PALAEONTOLOGY Caimans ruled ancient wetland A vast diversity of specialized crocodilian species dominated the mega-wetlands of South America before the Amazon River flowed, a remarkable fossil find has revealed.

Rodolfo Salas-Gismondi at the University of Montpellier in France and his colleagues found two bone beds in Peru containing seven species of crocodilian — the largest diversity of such species ever found in one place. As well as two known large- bodied species, they found five animals that are new to science, including several caimans with teeth that seem to be specialized for consuming shellfish. The numbers of these animals declined as Amazon River systems began forming around 10.5 million years ago, draining the wetlands and allowing more-generalist caiman predators to dominate. B 282, 20142490 (2015) IMMUNOLOGY Invading bacteria trigger DNA alarm Immune systems use a previously unrecognized DNA detector to identify invading bacteria. White blood cells called neutrophils recognize bacterial DNA, triggering a response that eventually kills the invaders. Zusen Fan and his colleagues at the Chinese Academy of Sciences Institute of Biophysics in Beijing found that a DNA-binding protein called Sox2 is also part of this bacterial surveillance system in mice and humans. They discovered that Sox2 binds to bacterial DNA, and that bacterial infections were worse in mice that had been engineered to have no Sox2 expression in neutrophils.

Infections were also worse in mice lacking another protein called TAB2, which interacts with Sox2. The findings could suggest new ways of treating infections, say the authors. Nature Immunol, org/10.1038/ni.3117 (2015) ANIMAL BEHAVIOUR Birds allow kin to borrow nests Female ducks recognize their kin and allow them to add eggs to their nests, but fight such attempts by non -relatives. Many birds try to trick others of the same species into incubating their eggs to avoid the associated energy costs. Malte Andersson at the University of Gothenburg in Sweden and his colleagues studied this ‘brood parasitism’ by filming the nests of High Arctic common eiders (. Somateria mollissima) for more than 4,100 hours.

They also analysed the proteins in egg albumen to determine the relatedness of the females that laid eggs in the nest, and found evidence for discrimination against non -relatives. In 65 nests studied, 1 1 contained eggs from two different females. At eight of these nests there were fights, and the two females laying eggs in each nest were unrelated. At three nests no aggression was observed, and the laying females were significantly more closely related than in the other eight. (2015) BACTERIOLOGY Altruistic bacteria share their food Starving bacteria can hook onto other bacterial species to share their nutrients.

Marie-Therese Giudici- Orticoni of Aix-Marseille University, France, and her colleagues cultured Clostridium acetobutylicum, which uses glucose to grow, and Desulfovibrio vulgaris, which uses lactate and sulfate, in a medium containing only glucose. Desulfovibrio vulgaris attached itself to C. Acetobutylicum, allowing it to share the other bacterium’s cytoplasm and proteins.

This altered the metabolism of D. Vulgaris, allowing it to grow with only glucose.

In a separate study, Christian Kost of the Max Planck Institute for 8 NATURE VOL 519 5 MARCH 2015 © 2015 Macmillan Publishers Limited. All rights reserved PAULDOMENICK/GETTY MPI CHEM. ECOL.; MPI MOL PLANT PHYSIOL SEAWIFS PROJECT, NASA/GSFC; ORBIMAGE THIS WEEK RESEARCH HIGHLIGHTS Chemical Ecology in Jena, Germany, and his colleagues mutated Escherichia coli and Acinetohacter haylyi so that they could not produce certain essential amino acids. When grown in a medium lacking the amino acid it required, E. Coli formed nanotubes up to 14 micrometres long to connect with and share the cytoplasm of nearby A. Haylyi, which was producing the amino acid.

In return, E. Coli provided A. Haylyi with the amino acid it needed. These bacteria function as interconnected entities rather than individuals, the authors suggest. Nature Commun. 6, 6283; 6238 (2015) NEUROSCIENCE Monkeys predict cooperation Monkeys use a distinct set of neurons to predict whether a fellow primate is likely to cooperate for a common good.

Keren Haroush and Ziv Williams at Harvard Medical School in Boston, Massachusetts, inserted electrodes into the brains of four rhesus macaques ( Macaca mulatto ) to record activity in hundreds of individual neurons in a specific area of the frontal lobe. They then trained different pairs of macaques to play a computer game displayed on a shared screen.

Both animals were rewarded with juice if they cooperated by selecting orange shapes instead of blue ones. A large subset of the animals’ neurons fired in a pattern that accurately predicted their partners’ intended, as-yet unknown, selections. This subset was distinct from other subsets that fired in patterns reflecting their own personal selections or the expected reward. Changes in these newly identified other- predictive’ neurons may be relevant in social behavioural disorders such as autism, the authors say.

Cell (2015) STEM CELLS Stem-cell hope for Parkinson’s Dopamine neurons derived from stem cells and inserted into a monkey’s brain reduce Parkinson’s -like symptoms over two years. Ole Isacson at Harvard Medical School in Boston, Massachusetts, and his colleagues created dopamine- producing midbrain neurons using induced pluripotent stem cells derived from the skin of cynomolgus monkeys (Macaca fascicular is). These neurons were introduced into the brains of three monkeys that lacked dopamine neurons — a model for Parkinson’s disease, in which monkeys have impaired motor skills and are less active than normal monkeys. In the most successfully treated animal, the stem-cell- generated neurons survived and grew axons, and dopamine production was restored. This animal gradually improved during the two years after treatment and showed normal activity, suggesting that transplantation of stem-cell- derived neurons could one day treat Parkinson’s disease. Cell Stem Cell (2015) AGRICULTURE Beetles felled by potato RNA Plants can be engineered to contain molecules that disrupt insect genes, fending off a superpest that is resistant to all major insecticides.

Ralph Bock of the Max Planck Institute for Plant Physiology in Potsdam, Germany, and his colleagues engineered tobacco and potato plants so that their chloroplasts SOCIAL SELECTION on social media Psychology journal bans P values A controversial statistical test has met its end, at least in one journal. Earlier this month, the editors of Basic and Applied Social Psychology ( BASP ) announced that the journal would no longer publish papers containing Rvalues, because the values were too often used to support lower-quality research. Authors are still free to submit papers to BASP with P values and other statistical measures that form part of null hypothesis significance testing’ (NHST), but the numbers will be removed before publication. “Basic and Applied Social Psychology just went science rogue and banned NHST from their journal.

Awesome,” tweeted Nerisa Dozo, a PhD student in psychology at the University of Queensland in Brisbane, Australia. But Jan de Ruiter, a cognitive scientist at Bielefeld University in Germany, tweeted: “NHST is really problematic”, adding that banning all inferential statistics is “throwing away the baby with the p-value”. 37, 1-2 (2015) Based on data from altmetric.com. Altmetric is supported by Macmillan Science and Education, which owns Nature Publishing Group. ONATURE.COM For more on popular papers: go.nature.com/ynfi49 (the cell’s photo synthetic structures) expressed RNA molecules that target vital insect genes.

Larvae of the superpest Colorado potato beetle ( Leptinotarsa decemlineata; pictured) died after nibbling leaves from the transgenic potatoes. By contrast, potatoes expressing the RNAs outside chloroplasts were not protected — probably because the plant’s internal defence mechanism stopped the RNAs from accumulating to sufficient levels. Science 347, 991-994 (2015) PALAEOCLIMATOLOGY A damp dispersal out of Africa Early humans would have had several rainy opportunities to move out of Africa and into the normally arid and challenging Arabian peninsula (pictured). Ash Parton of the University of Oxford, UK, and his colleagues discovered layers of sediments laid down by ancient rivers in southeast Arabia, which flowed for several long periods during the past 160,000 years.

Those wet spells could have enabled humans to push into the Arabian interior much earlier than some theories have suggested. Since at least 160.000 years ago, monsoon rains would have provided enough fresh water and plants to sustain human migration approximately every 23.000 years. Geology (2015) ONATURE.COM For the latest research published by NaturemsW: www.nature.com/latestresearch 5 MARCH 2015 VOL 519 NATURE © 2015 Macmillan Publishers Limited. All rights reserved 9 SEVEN DAYS The news in brief POLICY Chinese pandas increasingly isolated Chinas wild pandas have seen an increase in living space, and there are now 1,864 of them — compared with 1,596 a decade ago — all of which sounds like good news. But the results of a four-year survey announced on 28 February are not necessarily cause for celebration, and some experts are still concerned. Although living area has grown, panda populations are increasingly isolated, their habitats fragmented by roads, railways, dams and mines. Climate change threatens their food source, bamboo.

And it is not clear that numbers from the latest survey can be directly compared to the previous search around ten years ago. See go.nature.com/h93hle for more. Russian ISS plan Russia’s space agency Roscosmos announced on 24 February that it will continue its involvement in the International Space Station (ISS) until 2024 — a timeline that the United States had committed to last year. Roscosmos also added that after 2024 it will consider taking the Russian-built ISS modules and assembling them into a separate space station. Last year, as US- Russian tensions rose over the crisis in Ukraine, Russia’s deputy prime minister Dmitry Rogozin said that the country would pull out of the ISS by 2020. UK embryo law Mitochondrial donation will become legal in the United Kingdom after the final vote in a debate on 24 February that may set an international precedent.

The House of Lords voted overwhelmingly to approve regulations on human fertilization that would allow the creation of embryos with DNA from three people. The technique aims to prevent disease passing from mother to child through the mitochondria — the cell’s energy-producing structures, which have their own genes. Only 48 members of the Lords voted against the regulations, and 280 voted for them. The previous vote in the House of Commons was more closely contested (see go.nature.com/hyirxf). Green-card spouses Spouses of highly skilled foreign workers will soon be allowed to work legally in the United States, the US government announced on 24 February. The measure, due to take effect on 26 May, will apply to those married to individuals who are in the process of obtaining permanent residency (or a green card’) while on an H-1B visa — many of whom are scientists or engineers. The US Citizenship and Immigration Services estimate that nearly 180,000 couples will benefit from the policy change in its first year and 55,000 per year after that.

Pipeline veto US President Barack Obama vetoed legislation on 24 February that would have authorized the construction of a controversial pipeline intended to carry oil from Canada’s tar sands in Alberta to the US Gulf Coast. Republican majorities in both houses of Congress passed the legislation earlier this year, arguing that the Keystone XL pipeline would boost economic development; environmentalists argue that it would increase greenhouse-gas emissions because it promotes a dirty source of energy. The fate of the project now rests with the White House pending an environmental review by the US Department of State, which is expected in the coming weeks. PEOPLE Tributes to Spock Scientists on Earth and in space have paid tribute to Leonard Nimoy, who died on 27 February aged 83. NASA administrator Charles Bolden said that the actor, who played Star Trek's half- Vulcan science officer Mr Spock, was “an inspiration to multiple generations of engineers, scientists, astronauts, and other space explorers”, adding 10 NATURE I VOL 519 5 MARCH 2015 © 2015 Macmillan Publishers Limited. All rights reserved WILL BURRARD-LUCAS/N ATUREPL.COM TH E N EW YORK Tl M ES/REDUX/EYEVI N E THIS WEEK that “he made science and technology important to the story”.

Astronaut Terry Virts aboard the International Space Station tweeted an image of a Vulcan hand salute from orbit. US President Barack Obama hailed Nimoy as a “supporter of the sciences”, saying: “Long before being nerdy was cool, there was Leonard Nimoy.” Guilty plea A US scientist has pleaded guilty to fraudulent HIV vaccine research.

On 25 February, the Southern District of Iowa attorneys office said that Dong Pyou Han, formerly a researcher at Iowa State University in Des Moines, pleaded guilty to two counts of making false statements to the US National Institutes of Health. Han admitted adding human HIV antibodies to rabbit blood to make it appear as if his vaccine had induced an immune response in the rabbits. He will be sentenced in May and faces a maximum of 10 years in prison and a US$500,000 fine. Cosmic outreach Astrophysicist Neil deGrasse Tyson (pictured), director of the Hayden Planetarium in New York City, received the 2015 Public Welfare Medal from the US National Academy of Sciences, the academy announced on 26 February.

The medal recognizes Tysons efforts to excite the public about science. Most notably, he hosted last years 13 -part television series Cosmos: A Spacetime Odyssey, inspired by Carl Sagans classic 1980 Cosmos series. RESEARCH Ebola trial result Scientists reported the first positive results from a human clinical trial of a drug to treat Ebola on 25 February. A team led by researchers at the French Institute of Health and Medical Research announced that an antiviral drug, favipiravir, halved the mortality rate among people with low amounts of the Ebola virus in their blood. The death rate in the 40-person trial group was 15%, compared with 30% in the historical control group.

But the trial leaders caution that the study numbers are small, among other caveats. The results were announced at the annual Conference on Retroviruses and Opportunistic Infections in Seattle, Washington.

Minnesota review An external review commissioned by the University of Minnesota has found that “substantial change is necessary” in the way in which the university monitors clinical trials. The report, dated 26 February, states that the university’s ethical review committees are not sufficiently staffed or trained, and do not adequately consider the needs of vulnerable research subjects, such as children or people with mental illnesses. The report was intended to address faculty concerns that human-research oversight at the university may not be sufficient after a clinical-trial participant with a psychiatric disorder took his own life in 2004. Placenta project A mysterious but crucial organ, the placenta, is getting its day in the sun thanks to a US$4 1.5 -million investment by the US National Institutes of Health (NIH). On 26 February, the agency announced that the Human Placenta Project will fund eight or nine research teams to develop tools to monitor the placenta in real time as a proxy for tracking 90% not reporting/no data SEVEN DAYS COMING UP 6 MARCH NASA’s Dawn spacecraft will arrive at the dwarf planet Ceres in the main asteroid belt between Mars and Jupiter.

Go.nature.com/edumwi 9-11 MARCH The University of Tokyo has organized the 1st International Workshop on Topological Electronics at the Okinawa Institute of Science and Technology. This new area looks at the interaction between topology, electrical properties and quantum phenomena. Go.nature.com/ykezpt the developing fetus’s health. This could include imaging technologies and ways to detect fetal biomarkers in the mother’s blood. Much of the programme’s budget is redirected from the NIH’s $150 -million National Children’s Study, which was cancelled in December.

See go.nature.com/ohtjm5 for more. FUNDING India’s budget Scientists were disappointed by a below- inflation rise for research funding in India’s latest budget, announced on 28 February. The overall allocation for science stood at 419 billion rupees (US$6.8 billion), 3.4% more than was pledged last year. Renewable-energy research was slashed by 68%. But the country’s main agency for disbursing research grants, the Ministry of Science and Technology, received an 8% increase, slightly above inflation. See go.nature.

Com/26qfbq for more. ONATURE.COM For daily news updates see: www.nature.com/news VOL 519 NATURE 11 © 2015 Macmillan Publishers Limited. All rights reserved 5 MARCH 2015 MADS NISSEN/PANOS ROBOTICS Machines test their mettle in disaster - response contest p.14 VOLCANOES Indonesia and the Philippines top list of risky spots p.16 CANCER VACCINE A biotech company fails, but its vision lives on p.17 A RARE SPECIES Female, a physical scientist and in the developing world p.20 The trauma caused by death and fear is having long-term ramifications on the people of Sierra Leone PSYCHOLOGY Ebola’s mental-health wounds linger in Africa Health-care workers struggle to help people who have been traumatized by the epidemic.

BY SARA REARDON T he Ebola epidemic in West Africa may be fading, but its impact on mental health could linger for years. Survivors are often haunted by traumatic memories and face rejec- tion by society when they return home, and those who never contracted the disease may grieve for lost relatives or struggle to cope with extreme anxiety Aid groups and governments are battling to address the situation in a region that has little in terms of mental-health infrastructure.

There has been some progress: on 25 February, for example, the World Bank and the governments of fapan and Liberia announced a US$3 -million plan to provide psychosocial support in Liberia. But the fear and distrust of authorities that have helped Ebola to spread also make it difficult to manage the toll on mental health. And measures to contain the virus, such as quarantines, can limit access to the necessary treatment. “Were still seeing anxiety, and people in survival mode,” says Georgina Grundy Campbell, a mental-health nurse with the non-profit International Medical Corps (IMC) in Lunsar, Sierra Leone. “The majority of psy- chological problems are because the country is frozen, with nothing moving forward,” she says. West Africa is no stranger to crises. In the past two decades, the countries hit by the Ebola epidemic have seen civil war and unrest as well as torture and other human-rights abuses.

These events have sparked efforts to improve the nations’ limited mental-health-care sys- tems, including a programme funded by ► VOL 519 NATURE 13 © 2015 Macmillan Publishers Limited. All rights reserved 5 MARCH 2015 NEWS IN FOCUS ► the European Commission in which the first 20 psychiatric nurses graduated from the University of Sierra Leone in 2013. But clinical expertise is still scarce in the Ebola zone: Liberia has just one psychiatrist; Sierra Leone has none. Even the simplest interactions between peo- ple with Ebola, their families and health-care workers are complicated by the precautions needed to prevent infection.

Because doctors and nurses can wear their heavy personal pro- tective equipment only for short periods, they focus on providing treatment. Tasks such as counselling bereaved families are often left to mental-health providers from aid groups. In Sierra Leone, for instance, the non-govern- mental group Community Association for Psychosocial Services (CAPS) has redirected its 18 employees from assisting war survivors to helping people with Ebola and educating com- munities about the disease. “In this emergency, everyone’s kind of in slow motion, making sure that the health staff are safe,” says Cynthia Scott, a psychologist with Medecins Sans Frontieres (also known as Doctors Without Borders) who recently returned from Sierra Leone.

Surviving the virus presents its own chal- lenges. Some patients refuse to eat or leave their beds. Many blame themselves for contracting the disease.

And those who return home are often barred from housing complexes or work- places. That is a distinct contrast from the way in which communities hit by war or natural dis- asters typically rally around victims, says Inka Weissbecker, psychosocial adviser at the IMC in Washington DC. Non-governmental organizations are working to decrease the stigma using approaches such as portraying Ebola sur- vivors as heroes. They are also addressing another contentious issue — regulations that outlaw traditional burial rites — by pro- viding families with photos of their loved ones’ bodies, which offer some comfort. “I have heard people say, c If we cannot bury our people prop- erly, we feel our community is sick’,” Scott says. But some actions taken to limit Ebola’s reach are harder to deal with. Fear of spreading infec- tion among doctors and patients prompted the E.

Grant Mental Health Hospital in Monro- via — Liberia’s only such facility — to cease most of its operations last autumn. The facility has discharged most of its patients, including sev- eral dozen with psychotic conditions.

“There’s no doubt there’s an increase in the number of people in the streets because the hospital is still not functioning at the normal level,” says Benja- min Harris, Liberia’s only psychiatrist. Efforts to build treatment capacity in West Africa are showing encouraging signs. The programme in Liberia will, over a three-year period, deploy mental-health clinicians in schools, among other actions.

The Liberian Ministry of Health lists mental health as a prior- ity in its Ebola-recovery plan, along with issues such as maternal care (see page 24) and HIV. And in Sierra Leone, CAPS has treated roughly 1,500 people affected by Ebola. These developments are part of a broader shift in the global health community’s atti- tudes toward mental health. The World Health Organization increasingly addresses psycho- logical care in its reports, and donors to groups such as the IMC are becoming more amenable to supporting mental-health programmes. But there is still much work to be done to ensure that psychological care is a priority in the Ebola response, Weissbecker stresses. “We have to be vigilant about this,” she says, “and make sure it stays on the radar.” ■ “The majority of psychological problems are because the country is frozen, with nothing moving forward. ” TECHNOLOGY Robo -rescuers battle it out Nimble bots rise to the challenge in DARPA competition.

BY BOER DENG W hen the humanoid robot SAFFiR gets a shove, it reflexively moves to maintain its balance. SAFFiR can also walk over uneven terrain, turn its head to scan its surroundings and — with the help of a human operator — reach out to grasp objects.

Built by a team at Virginia Tech in Blacksburg, SAFFiR is a firefighting robot and a prototype for one that will compete in the final stage of the DARPA Robotics Challenge (DRC), a con- test run by the US Defense Advanced Research Projects Agency. The aim is to produce robots with improved mobility, autonomy and respon- siveness to human commands. On 5 March, DARPA will announce the 25 finalists who will vie for the US$2-million first prize at the final event in June.

Most advanced robots today follow preset instructions in familiar environments, such as a factory floor, or are almost entirely remotely controlled, says Gill Pratt, a programme man- ager at DARPA who is running the contest. But there is a need for shrewder, nimbler machines that can operate in less-predictable situations. A robot developed by Japanese company Schaft takes the DARPA Robotics Challenge in 2013. For example, radiation from the 2011 Fukush- ima nuclear meltdown in Japan made it unsafe for people to manage the contamination. The robots that could be deployed for clean-up were slow and maladroit, and could do little more than survey the damage.

DARPA set up the contest to spur the development of robots that might perform better in future disasters, and several rounds of the competition have been held since the event’s launch in 2012. A key to winning will lie in a robot’s ability to do things on its own, such as deciding how high to lift a leg to climb a step, or tracking its loca- tion relative to a target object. During trials in December 2013, robots had to complete tasks such as shutting off a valve, climbing a ladder and driving a car through a winding speedway course. Those with greater autonomy per- formed better, according to an analysis by Holly Yanco, a computer scientist at the University of Massachusetts at Lowell. Robots were faster and errors were easier to fix when they needed less human input. For the final round, the machines will com- pete with a time limit, without an external 14 NATURE VOL 519 5 MARCH 2015 © 2015 Macmillan Publishers Limited.

All rights reserved AP/PA BERTIL ENEVAG ERICSON/TT/EPA/CORBIS NEWS IN FOCUS Former IPCC head Rajendra Pachauri (left) consults with potential successor Thomas Stocker. POLICY UN climate panel charts next steps Intergovernmental Panel on Climate Change prepares for new leadership and another assessment of climate science. Power source and sometimes without communication with their operators. This mimics real disaster scenarios, in which connectivity can be spotty DARPA expects that this constraint will encourage teams to increase their robots’ capacity to map out, plan and act independently “Success at this level would be a huge achievement,” says Pratt. Robots have become reasonably good at sensing and moving, says Henrik Chris- tensen, chair of robotics at the Georgia Institute of Technology in Atlanta.

Remote sensors on SAFFiR, for example, measure force and body position (part of what allows the robot to find its centre of gravity); cameras and software let it monitor distance and potential obstacles. CHIMP, a robot built by a team at Carnegie Mellon University in Pittsburgh, Pennsylvania, transitions deftly from trundling along on four tank treads to standing on two. But the machines are “not much good at making judgements, like deciding if some- thing is a drill or a cup, or figuring out which is relevant to what it needs to do”, Chris- tensen says. “These things turn out to be very hard, and humans are much better at them.” DIVISION OF LABOUR Some teams want to better translate what a robot sees into something that a human operator can easily understand. The goal is to create an efficient human-robot team that is “more like having two humans, where one directs the other”, says Todd Danko, who leads a DRC team from defence contractor Lockheed Martin. In fact, Yanco’s analysis found that teams with better-designed human-robot interface platforms were better at completing contest tasks. “I think a big part of this contest is that it will get people to embrace a kind of shared autonomy’ between the humans and the robots,” says James Kuffner, a roboticist at Google in Mountain View, California.

“That means thinking about what’s necessary for the human to do, for the robot to do, and for how to tell that to the robot.” DARPA-sponsored robot contests in the mid-2000s focused on autonomous trans- port and were driven by an interest in taking human couriers off the explosive -strewn streets of Iraq and Afghanistan. These races helped to spawn interest in driverless cars from companies such as Google. In more recent years, the defence depart- ment has recommended that the military change its approach to autonomous systems and focus on collaboration between people and technology. Unlike autonomous trucks and unmanned drones, the robots under development for the current competition will be accomplices — not mere substitutes — in helping humans to get difficult jobs done. ■ BY JEFF TOLLEFSON D espite calls for change, the next United Nations climate assessment will take much the same form as the last one, the panel charged with producing the recurring reports announced on 27 February. The decision comes just days after the panel’s long-time leader resigned in the middle of a sexual-harassment investigation. Meeting in Nairobi from 24 to 27 February, the United Nations Intergovernmental Panel on Climate Change (IPCC) made several minor adjustments to its assessment process.

The changes aim to engage more scientists, in part by boosting the representation of devel- oping nations in the group’s governing body. But the basic framework will continue to com- prise a comprehensive assessment published every five to seven years plus two or three spe- cial reports on specific topics.

The fifth and most recent IPCC climate assessment, which was completed last year, concluded that it is “extremely likely” that humans are responsible for the bulk of recent global warming. “The overall structure remains, but some key aspects of its mode of operation have been improved to facilitate a fuller participation of all scientists, in particular from developing countries,” says IPCC vice-chair Jean-Pascal van Ypersele, a climatologist at the Catholic University of Louvain in Louvain-la-Neuve, Belgium. “This was a key thing I think the IPCC needed to do.” The meeting follows the sudden departure of Rajendra Pachauri, who has headed the IPCC since 2002 and whose term was due to end in October. Pachauri is under investiga- tion over allegations that he sexually harassed a colleague at the Energy and Resources Insti- tute in New Delhi, of which he is director. He has denied the claims but elected to step down on 24 February, soon after announcing that he would not be attending the Nairobi meeting. “We cannot ignore the resignation of Dr. Pachauri, but the allegations against him.

Do not relate to the IPCC,” said IPCC secretary Renate Christ during a press conference on 27 February. Christ said that the panel will, however, ensure that it maintains an atmos- phere in which “everyone’s rights are respected and upheld”. Ahead of the meeting, some scientists involved in the IPCC argued that the ► VOL 519 NATURE 15 © 2015 Macmillan Publishers Limited. All rights reserved 5 MARCH 2015 NEWS Mount Merapi, the most active volcano in Indonesia, erupts every few years. NATURAL HAZARDS Global volcano risk quantified UN assessment aims to save lives by aiding planning. IN FOCUS ► assessment process is too slow and requires too much time from the more than 2,000 scientists from around the world who volunteer for duty.

Some have advocated that the IPCC put less energy into monumental assessments and more into shorter reports that focus on major scientific and policy debates. During the last major assessment, the IPCC released special reports on renewable energy and the risks of extreme weather, but even those were major undertakings. Christopher Field, co-chair of the work- ing group on impacts and adaptation for the most recent assessment, says that there are ways to streamline the process, but main- tains that the value of the IPCC comes from the give and take between scientists and governments. “Operationally, it is hard to imagine a way to capture this unique value without key process steps, includ- ing multiple rounds of monitored review and line-by-line approval of summaries for policy-makers,” he says. OPEN UP At the meeting, IPCC members said that the next assessment should have a greater focus on specific regions and include a broader review of non-English scientific literature, with more involvement of sci- ence writers and communications experts to help reach a broader range of people. The panel also wanted to open itself up to researchers who have been seeking access to the closed-door meetings in an effort to study the assessment process and the institution itself; research proposals will be evaluated on a case-by-case basis.

“That is indeed a major step forward toward both increased transparency of the IPCC process and eventually finding ways to improve it,” says Michael Oppenheimer, a climate scientist at Princeton Univer- sity in New Jersey who is part of a team of researchers seeking such access. Oppenheimer has advocated reforms that would emphasize smaller, faster assess- ments while decreasing the workload for scientists. He says that the latest decision largely represents “business as usual”, but does open the door for improvements. In particular, he credited the IPCC for empha- sizing communications and engagement with developing countries.

“This is impor- tant and needs to be done,” he says. The IPCC will hold its leadership election in October. Candidates include van Ypersele and Thomas Stocker, a climate scientist at the University of Bern who co-led the work- ing group that wrote the physical- science portion of the report during the most recent assessment. Field, who is founding director of the department of global ecology at the Carnegie Institution in Stanford, California, says that he, too, is likely to run.

■ BY ALEXANDRA WITZE S wept away by mudslides, entombed in lava or suffocated under ash, nearly 280,000 people have died in volcanic eruptions during the past four centuries, but only now has humanity managed to quantify the risk posed by these fiery phenomena. The first detailed assessment of global volcanic risk — part of a larger international hazard assessment released on 4 March by the United Nations Office for Disaster Risk Reduction — aims to save lives by providing better information for risk planners and by showcasing effective response measures.

“For the first time, we really have a shared understanding of volcanic activity at the global scale,” says Jean-Christophe Komorowski, a volcanologist at the Institute of Earth Physics in Paris, who contributed to the report. “This is a major turning point.” Eight hundred million people live within 100 kilometres of a volcano that could erupt. But the hazards differ greatly from place to place.

High in the snow-capped Andes, an eruption might melt ice and send floodwaters rushing into nearby villages. In southeast Asia, a pow- erful eruption might blast ash over a wide area, causing roofs to collapse under the weight. The report aims to put hard numbers on exactly who is at risk. It comes from a UK-led international network of institutions called the Global Volcano Model, working with the International Association of Volcanology and Chemistry of the Earths Interior.

Team leaders sifted through a database of nearly 9,500 eruptions over the past 10,000 years kept by the Smithsonian Insti- tution in Washington DC. They noted how often a particular volcano had erupted and what kind of physical hazards it posed. Then they tallied the number of people who now live within 10, 30 and 100 kilometres of that volcano and whether they live in places where eruptions have killed people before (see ‘Mass destruction ).

The result is a com- plete catalogue of the highest-risk volca- noes and a list of countries ranked by the number of residents in harms way. Researchers were surprised to find risk in places not typically thought of as highly volcanic. The Auvergne region of France, for instance, has been quiet in historic times. But it has had eruptions in the past few thousand years, putting it relatively high on the hazard scale because so many people live nearby.

In New Zealand, the Auckland volcanic field — the eruptive history of which is not par- ticularly well known — lies directly under the country’s biggest city. “Volcanoes are extremely attractive areas to 16 NATURE VOL 519 5 MARCH 2015 © 2015 Macmillan Publishers Limited. All rights reserved OSCAR SIAGIAN/REDUX/EYEVINE SOURCE: GLOBAL VOLCANIC MODEL/IAVCEI NEWS IN FOCUS MASS DESTRUCTION More than half of the fatalities caused by volcanic eruptions in the past four centuries occurred in just five major events that killed an estimated 162,928 people. Today, more than 90% of the volcanic risk is concentrated in five countries.

Nevado del Ruiz 1985 300 •; 23,187 fatalities — Total from all 533 fatal incidents Pelee 1902 Total with 5 biggest incidents removed 28,800 fatalities — Total with 10 biggest incidents removed Krakatau 1883- 200 36,417 fatalities i n ~o c ro i n 33 O CO CD 03 H — ' 03 M— CD >=5 E Z5 o Tambora 1815 60,000 fatalities 100 I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I l l l l I I I I I I I I I I I I I I I I 1650 1700 1750 1800 1850 1900 1950 2000 Japan Ethiopia 6. 9% live,” says Jenni Barclay, a volcanologist at the University of East Anglia in Norwich, UK. Volcanic soil is often fertile and the altitude pro- vides good living conditions in hotter climates. Worldwide, 62 volcanoes fell into the high- est risk category, meaning that they have been recently active and lie close to a lot of people. Indonesia tops the list of most threatened countries, with 77 historically active volcanoes, including Mount Merapi, which erupts fre- quently near the city of Yogyakarta. But by a different measure, small volcanic islands — such as Montserrat in the Caribbean — are the most vulnerable.

When these island nations start to rumble, all their citizens must flee or risk death. In these places, uncertainty has its cost: a controversial 1976 evacuation of the Caribbean island of Guadeloupe left resi- dents angry when no major eruption happened. Just because a volcano ranks as hazard- ous does not mean that people living near it are sitting ducks. If a volcano has enough scientific monitoring equipment on it, and a well-organized local response, then the risk to human life can be reduced, says Stephen Sparks, a volcanologist at the University of Bristol, UK, and a lead author of the report. At Merapi in 2010, the authorities used infor- mation about physical changes in the volcano Indonesia 66% to evacuate hundreds of thousands of people before a large eruption, saving many lives. “We want to showcase what volcanologists around the world are doing,” says Sue Loughlin, a volcanologist at the British Geological Survey in Edinburgh and another leader of the survey In Ecuador, around the Tungurahua vol- cano, local volunteers serve as a network of Philippines Mexico Other 10. 7% vigtas or Volcano watchers’.

They watch for changes in the mountain and radio in to the nearby volcano observatory every evening with their reports (J. 3, 1 1; 2014).

Such initiatives could trans- late to other volcanically active regions, says Barclay. “We can learn much more by bringing all this knowledge together.” ■ BIOTECHNOLOGY Therapeutic cancer vaccine survives biotech bust Pharmaceutical company rescues landmark prostate -cancer treatment, Provenge. BY HEIDI LEDFORD T he first therapeutic cancer vaccine to be approved in the United States will stay on the market despite the financial col- lapse of the trailblazing biotechnology com- pany that developed it. The vaccine, Provenge (sipuleucel-T), was purchased on 23 February by Valeant Pharmaceuticals of Laval, Canada, which paid US$415 million for the prostate- cancer treatment and other assets of the bankrupt Dendreon Corporation. The now-defunct Dendreon, of Seattle, Washington, made history in 2010 by showing that complex treatments made fresh for each patient could win regulatory approval, and could be expanded beyond the realm of spe- cialized academic hospitals.

Industry took note: today, experimental cancer therapies that spur patients’ immune cells to attack tumours are among the hottest properties in biotechnology. “Dendreon had vision and foresight,” says Usman Azam, head of cell and gene therapies at Novartis, a Swiss pharmaceutical company that has purchased one of Dendreon’s manu- facturing plants to fuel its own cell-therapy efforts. “Don’t view Dendreon as a failure: it paved the way” But although Dendreon created the market for such cell therapies, it ultimately could not survive in it. Provenge is made by harvesting a patient’s dendritic cells — a type of immune cell — and then mixing them with a protein that is particu- larly abundant in prostate tumours. This primes them to recognize and attack the tumour; the cells are then infused back into the patient.

The technique was pioneered in the early 1990s by Edgar Engleman, an immunologist at Stanford University in California, who had seen promising results in animal studies of a different cancer, lymphoma. He teamed up with fellow Stanford immunologist Samuel Strober to work out ways to make the process more efficient. When the two pitched their idea for a com- pany to investors, they had few clinical data and were too optimistic about how fast the treatment could reach patients, says Strober.

The company was an enormous gamble: har- nessing the immune system to fight cancer was still a controversial idea, and no other company had marketed a therapy so person- alized and labour-intensive. “But at that time it was a little different from now,” says Strober. “Companies were getting funded on the basis of promise, rather than actually looking at their capacity for early commercial success.” Engleman and Strober founded Dendreon in 1992; the US Food and Drug Administra- tion approved Provenge in 2010. The approval was celebrated as an impor- tant proof of concept by researchers working on cancer vaccines and other treatments that stimulate immune responses to the disease. But Dendreon, already strained by the long wait for approval, soon ran into financial difficulty ► VOL 519 NATURE 17 © 2015 Macmillan Publishers Limited. All rights reserved 5 MARCH 2015 NATSUKI SAKAI/AFLO/ALAMY NEWS IN FOCUS ► The United States’ publicly funded Medicare system decided in 20 1 1 to pay for Provenge treat- ment.

But confusion over how the cost of the vaccine would be reimbursed by private insur- ance companies left many US doctors hesitant to use it, says Corey Davis, an analyst at Canaccord Genuity, an investment bank based in Toronto, Canada. When revenues came in far below the company’s initial estimates, Dendreon failed to adjust its operations accordingly, Valeant chief Michael Pearson told investors on 23 February. Provenge is, at first glance, an odd purchase for Valeant, a company known for acquiring relatively simple, established products — for example, it controls 10% of the US contact-lens market. But Valeant saw an opportunity to cut costs and improve how the vaccine is marketed to doctors, and thinks it can make back its investment in less than two years, says Davis.

The vaccine’s rescue is a relief to Engleman, who had feared that Provenge might disappear along with Dendreon. As the company strug- gled financially, the scientists who founded it watched helplessly from the sidelines. “This was our baby,” says Engleman. “It was extraor- dinarily frustrating. There was nothing we could do.” In retrospect, Engleman says, some early scientific choices may have exacerbated Den- dreon’s struggle.

He notes that the company decided not to develop ways to freeze the stimulated immune cells, which could have simplified the pro- “ Don’t view cedure and lowered Dendreon as a its cost. Failure: it paved Both scientists the way. ” lament the choice of prostate cancer as the inaugural disease target of the technology.

Although the early lymphoma data had been very promising, recalls Engleman, the com- pany decided to switch to a more common cancer with a bigger potential market. And prostate cancer had another advantage: peo- ple can live without a prostate, which helped to calm fears (since proved unfounded) about what would happen if the primed immune cells attacked healthy tissue. But the results in prostate cancer were not as dazzling as Engleman had hoped on the basis of his animal results in lymphoma. Dendreon did extend survival in some people with advanced prostate cancer, but by a median of only four months (P.

Kantoff et al. 363, 411-422; 2010). Last week, the UK National Institute for Health and Care Excellence advised that at more than £47,000 (US$73,000) per course of treatment, Provenge is too expensive to justify its use by the National Health Service. The Dendreon experience has not dampened Engleman’s enthusiasm for entrepreneurship. He and Strober, along with other collabora- tors, have teamed up on a company that aims to develop a technique to reduce the likelihood that recipients of transplanted organs will develop an immune response to the new tissue.

They are again on the hunt for funding, but this time the team is backed by more than a decade of clinical-trial data that supports the method. “We’re thinking that this one will progress a lot faster than the Dendreon thing,” says Strober. ■ HYDROLOGY Slick idea proposed to stretch water supplies Thin coating that cuts evaporation from lakes offers hope for drought -ridden United States. BY MATTHEW WALD I n the southwestern United States, where years of drought are leading water man- agers to consider drastic water-provision measures such as desalination and cloud seeding, entrepreneurs have suggested reviv- ing a technique that was tried and abandoned half a century ago.

They propose to stretch dwindling water supplies by slowing down evaporation from reservoirs by means of a surface barrier of cheap, non-toxic, biodegrad- able chemicals just one molecule thick — two- millionths of a millimetre. The technology is far from proven, but it showed some potential in field tests in Texas last year. Worldwide, more water evaporates from reservoirs than is consumed, and the losses are especially acute in hot, dry regions. The idea of a coating to slow evaporation has been floated for decades, and government researchers in the United States and Australia have investigated the concept.

The approach, which generally involves chemicals derived from coconut or palm oil, is already used on small bodies of water such as golf-course ponds and swimming pools. But it has not been practical for larger bodies because wind tends to break the layer apart, says Moshe Alamaro, an engineer at the Massachusetts Institute of Technology in Cambridge. Last summer, a field test in Texas attempted to overcome that problem.

The US$325,000 test ran from July to October on Lake Arrowhead, a 21 -square-kilometre reservoir that serves the city of Wichita Falls. Flexible Solutions Inter- national, a company in Victoria, Canada, that makes evaporation-reducing coatings for small water bodies, programmed a boat to run on autopilot and make a grid pattern across Lake Arrowhead spreading the coating behind it. An analysis published in January by the Texas MORE ONLINE TOP NEWS Japanese monitoring effort tracks food radioactivity at Fukushima go. Autocad 2008 Serial No And Activation Code on this page. nature.com/ Iv3rgr MORE NEWS • Mapping a giant virus in 3D go.nature.com/xzsp6s • Ancient DNA reveals how wheat came to prehistoric Britain go.

Nature, com/dradnn • Tropical forest losses outpace UN estimates go.nature.com/ozbvuj Q&A The science behind the world’s first stem-cell therapy go. Com/rpbyp3 18 i NATURE VOL 519 5 MARCH 2015 © 2015 Macmillan Publishers Limited. All rights reserved CONTRASTO/EYEVINE NEWS Drought-stricken Lake Arrowhead in Texas was coated with a film that reduced evaporation by up to 15%. Sg Water Development Board suggested that the 0 results were promising, but not conclusive 1 (see go.nature.com/zrcozd). Compared with a x similar reservoir nearby, the treated reservoir I lost an estimated 15% less water to evapora- 8s tion. But the analysis could not attribute all of - 1 that difference to the coating, because it did not account for variables such as stream inflows and seepage outflows. The coating probably helped, says Mark Wentzel, a hydrologist for the Texas Water Development Board and co-author of the report, but “I wouldn’t stake my life on it.” Alamaro suggests that a more aggressive technological approach is needed.

Radar instruments carried on a blimp or drone could reveal where the reservoir’s coating has broken up, he says, by sensing the way that it damp- ens ripples on the water. More coating can be added when and where it is needed, potentially cutting evaporation by 70%, he estimates. Alamaro has founded a company, More Aqua in Cambridge, Massachusetts, that is trying to develop a system of diffusers and skimmers to keep a body of water thoroughly and continuously covered.

The company is planning its own pilot test near Palo Alto, California, this summer using its own coating. It plans to offer its services in IN FOCUS exchange for owning the water that it saves, and to sell that on the open market in the state, where the cost of water for irrigation can exceed $1,000 per acre-foot (1,233 cubic metres). Assuming evaporation savings of 15%, says Daniel O’Brien, president of Flexible Solutions, the $160 cost of saving one acre-foot of water with the coating compares favourably with a Texas market price of $345-700 per acre-foot of water. Water consultant William Mullican of Lubbock, Texas, who is retired from the Texas water board, says that although the Lake Arrowhead results were unclear, this is also often the case in field tests of other water- sparing techniques such as cloud seeding and cutting back brush to keep it from sucking moisture from the soil. Given the Texas test’s promising result and the fact that the ongoing drought in the state is severe, he says, there is every reason to try the technique out again, “unless it starts raining”. ■ CORRECTION The News Feature The painful truth’ ( Nature 518, 474-476; 2015) omitted Marks’ first name and affiliation. Donald Marks is the co-founder and chief science officer of Millennium Magnetic Technologies.

© 2015 Macmillan Publishers Limited. All rights reserved LARRY SMITH/EPA/CORBIS NEWS Drought-stricken Lake Arrowhead in Texas was coated with a film that reduced evaporation by up to 15%. Water Development Board suggested that the results were promising, but not conclusive (see go.nature.com/zrcozd).

Compared with a similar reservoir nearby, the treated reservoir lost an estimated 15% less water to evapora- tion. But the analysis could not attribute all of that difference to the coating, because it did not account for variables such as stream inflows and seepage outflows. The coating probably helped, says Mark Wentzel, a hydrologist for the Texas Water Development Board and co-author of the report, but “I wouldn’t stake my life on it.” Alamaro suggests that a more aggressive technological approach is needed. Radar instruments carried on a blimp or drone could reveal where the reservoir’s coating has broken up, he says, by sensing the way that it damp- ens ripples on the water.

More coating can be added when and where it is needed, potentially cutting evaporation by 70%, he estimates. Alamaro has founded a company, More Aqua in Cambridge, Massachusetts, that is trying to develop a system of diffusers and skimmers to keep a body of water thoroughly and continuously covered. The company is planning its own pilot test near Palo Alto, California, this summer using its own coating. It plans to offer its services in IN FOCUS exchange for owning the water that it saves, and to sell that on the open market in the state, where the cost of water for irrigation can exceed $1,000 per acre-foot (1,233 cubic metres). Assuming evaporation savings of 15%, says Daniel O’Brien, president of Flexible Solutions, the $160 cost of saving one acre-foot of water with the coating compares favourably with a Texas market price of $345-700 per acre-foot of water. Water consultant William Mullican of Lubbock, Texas, who is retired from the Texas water board, says that although the Lake Arrowhead results were unclear, this is also often the case in field tests of other water- sparing techniques such as cloud seeding and cutting back brush to keep it from sucking moisture from the soil.

Given the Texas test’s promising result and the fact that the ongoing drought in the state is severe, he says, there is every reason to try the technique out again, “unless it starts raining”. ■ CORRECTION The News Feature The painful truth’ ( Nature 518, 474-476; 2015) omitted Marks’ first name and affiliation. Donald Marks is the co-founder and chief science officer of Millennium Magnetic Technologies. © 2015 Macmillan Publishers Limited.

All rights reserved BY KATIA MOSKVITCH P atchanita Thamyongkit was waiting patiently near the stage at a conference on the importance of science for Thailand, when the organizer rushed up to her and asked whether she had seen the next presenter, Professor Thamyongkit “That’s me,” she replied. An awkward pause followed. “Oh, I thought you were his secretary,” came his reply. The presenter was probably more embarrassed by the 2008 inci- dent than Thamyongkit, who is used to being taken for a secretary. She is a physical organic chemist at Thailand’s biggest scientific estab- lishment, Chulalongkorn University in Bangkok, where she has won several awards for her work. But senior female scientists are a rarity in Thailand: top science positions are scarce, and many women are forced out of research because of cultural expectations that they will take care of their households, raise children and help ageing parents.

Women around the world continue to face major challenges in pur- suing a research career — particularly in the physical sciences. In the United States, women make up nearly half of college-educated work- ers and working life scientists, but only 30% of physical scientists. The gender gap widens higher up the professional scale.

There is much debate about why: discrimination, conscious and unconscious bias in hiring and promotion, lack of role models and the demands of bearing and caring for children are all thought to play a part. In developing countries, female scientists can face even higher cul- tural and societal barriers, such as overt sexism, and a lack of con- traception, reproductive choice or access to education. Many live in regions with desperate poverty, few high-quality schools, political insta- bility and sometimes civil conflict. “There is a great, growing interest in science and engineering among women in developing countries,” says Romain Murenzi, a physicist and former Rwandan science min- ister who is now executive director of TWAS, the World Academy of Sciences, which promotes the advancement of science in develop- ing countries.

Yet, he says, “women face obstacles from their earliest years, and across the landscape of their lives”. The situation varies enormously from one place to the next: figures from the United Nations Educational, Scientific and Cultural Organization (UNESCO) show that women in Thailand make up just over half of science doctoral students and researchers, whereas in Nigeria, those figures are 24% and 23%.

Nature talked to three women who are in this minority of minori- ties — working in physical sciences in developing countries — to find out what challenges they have faced and how they overcame them. Their stories highlight two of the ingredients for success: a supportive family and a huge dose of determination. Becoming a leading scientist involves “convincingyour family first”, says Thamyongkit, “and then, for the rest of your life, going out of your way to prove to everyone that you’re actually really good”. THAILAND Patchanita Thamyongkit THAMYONGKIT LIVES WITH HER ELDERLY PARENTS in a narrow, three-storey house in blaring central Bangkok. The neigh- bourhood is a sea of concrete, with wall-to-wall houses. When she was young, her parents ran an automobile-parts shop and a book store.

They were ambitious for their daughter, and wanted her to become a doctor. “I am lucky in the sense that my parents have always supported me,” says Thamyongkit — even when she chose to study physical sci- ences instead of medicine at Chulalongkorn University. Thamyongkit embarked on an academic world tour: she did a PhD in Germany and took a postdoctoral post in the United States before returning, speaking two foreign languages, to join the chemistry depart- ment at Chulalongkorn in 2005. She researches novel organic materials for optoelectronic applications, such as energy-efficient solar cells. Last November, she won a L’Oreal-UNESCO prize for women in science.

Equal proportions of men and women participate in Thai science edu- cation and scientific research as a whole. At Chulalongkorn, roughly 25% of faculty members are women in physics and 35% in chemistry, propor- tions roughly similar to those in the United States. Many universities have nurseries and schools on campus, and some researchers say that they do not perceive a gender gap at all.

The country elected its first female prime minister, Yingluck Shinawatra, in 201 1. But as in other nations, the academic pipeline for women is leaky.

“Really, really few actually reach the top,” says Supot Hannongbua, dean of the faculty of science at Chulalongkorn. “Researchers maybe publish one paper a year — its very difficult for them.” Out of 80 fac- ulty members in the department of chemistry, he says, there may be between 5 and 7 people doing outstanding research or in senior posi- tions, and rarely is one a woman. Part of the problem is that top research jobs are rare. Just 0.2% of the country’s gross domestic product goes on research, and only around 20 of Thailand’s 160 or so universities have proper research facilities. With so few opportunities, women often lose out. Most of the 12 female graduate students in Thamyongkit’s lab late last year said that they wanted to work in industry, care for their families, or both.

That efflux is also driven by Thai society’s traditional expectations. Many women work, but it is assumed that they will get married and shoulder caring and domestic duties.

Although overt sexism is frowned on, discrimination persists. “If a man and a woman candidate with exactly the same characteristics apply for a top scientific position, the 20 NATURE VOL 519 5 MARCH 2015 © 2015 Macmillan Publishers Limited. All rights reserved FEATURE NEWS Women are under - represented in physical sciences and in science in the developing world.

Meet three who beat both sets of odds. Patchanita Thamyongkit is a physical organic chemist at Chulalongkorn University in Bangkok.

Man is more likely to get hired,” says Hannongbua. Some advertisements for industrial jobs state that the applicant must be a man. Women can also struggle to make the right connections, says Tyrell Haberkorn, who studies Thai politics and history at the Australian National University in Canberra.

“Women in Thailand face everyday sexism of the boy’s-club variety, in which important decisions and rela- tionships are forged outside the workplace and instead in the male-only spaces in which men go out and eat and drink together.” One female chemist at Chulalongkorn, Parichatr Vanalabhpatana, says that she had to learn to drink beer to be accepted by her male colleagues. The Thai government has tried to institute change. Shinawatra pro- moted gender equality through a National Development Fund for Women, which offers low- interest loans to further womens welfare and occupations; and in 2007, Thailand criminalized domestic violence. But Thamyongkit, Hannongbua and others say that the government should do more. “I still insist that Thailand has no particular and serious campaign to encour- O NATURE.COM age women in science,” says Thamyongkit.

Over- For a video of coming entrenched societal attitudes “would take Thamyongkit, see; what would amount to a social revolution in how go.nature.com/zsausd gendered roles are conceived”, says Haberkorn. “But in truth, I think that continuing to open up education, particularly tertiary education, to a broader and broader group of people is the most concrete strategy.” Thamyongkit has found her own way through.

In her twenties, she decided to not have a family. “I did want to have kids before, but if ten years ago I had had a family, I would have never managed to get to the same level in my career where I am now,” she says. Now 38, she says that it is probably too late. As she walks through the campus, Thamyongkit passes a temple, where she takes a few seconds to stop, kneel and pray. “I’m not religious,” she says. “But I meditate, I say a few words to reinforce all the positive things in my life, to keep the positive energy flowing.” At the end of the day, as Thamyongkit sits down with her family for dinner, her parents say that they would love to have a grandchild. But they don’t pressure her, she says, and she is grateful for that.

“My rela- tives want to know why I don’t have a family. They say, ‘You don’t look that bad, so why? Why?’ But my parents know I am happy, and for them it’s the main thing.” “Thailand has no particular and serious campaign to encourage women in science.

” 5 MARCH 2015 VOL 519 NATURE 21 © 2015 Macmillan Publishers Limited. Ddx3216 Software Download. All rights reserved NEWS FEATURE NIGERIA Rabia Salihu Sa’id ON A SUNDAY MORNING IN APRIL 2012, Rabia Salihu Said, a 52-year-old professor of atmospheric and space-weather physics at Bayero University in Kano, northern Nigeria, was at home with her six children when she heard some shocking news. Fighters from the mili- tant Islamist group Boko Haram had stormed a packed church on the university campus, killing 16 people and wounding many others, mostly students and academics. Said lost two of her colleagues and friends in the attack, which was part of Boko Haram’s campaign to build an Islamic state and stamp out Western education. Said knew that she could have been one of those killed — but it did not stop her from teaching or doing research, and neither have further Boko Haram attacks. “There’s a lot of security at the university now, you can’t come in without being searched,” she says. “But we are not afraid.” Even before these threats, Said’s career was riddled with challenges.

A growing number of girls in Nigeria receive an education, but in the north of the country — where Sa’id grew up — they often receive little school- ing and get married in their teens, says Said’s colleague Babatunde Rabiu, director of the Centre for Atmospheric Research at Nigeria’s National Space Research and Development Agency in Anyigba. The country is rated poorly in a 2014 index compiled by the Organisation for Economic Co-operation and Development to measure discrimination against women in areas such as law and social norms. Within science, physics is still very much considered a male’ subject, says Rabiu. A report 1 that Sa’id co-authored in 2013 found that 5-20% of students enrolled in physics in Nigerian universities were women, and UNESCO figures show that women make up 24% of doctoral students in all areas of science. “It is common for single women who go for further degrees to be mocked by men and even by some females,” says Rabiu; traditionally, women are expected to marry and stay at home. Like Thamyongkit, Sa’id overcame these hurdles thanks to the encour- agement of her family.

Her father, an officer in the Nigerian Army, encouraged all of his children to pursue education and hoped that his daughter would become a doctor. Instead, she married straight out of school, at the age of 1 8. When her first son was born with a club foot, she shelved her higher- education plans. Soon, two more children followed. Aged 29, she decided to go to university at last.

She did not have a high enough grade in chemistry to enter medicine, so she opted for physics. But first, there was the pressing question of how to pay for university. She sold a gold necklace from her bridal dowry to pay for the registra- tion, and she ran a nursery school to cover the rest. “Many women would not be able make it like I did, and would have to give up the dream of a university degree if they have no financial support,” she says. Months after Sa’id began her studies, her fourth child was born with sickle-cell anaemia — an incurable genetic disorder.

With two children needing medical care, “It was incredibly challenging for me”, recalls Sa’id. “I was really in and out of hospitals.” Her extended family and friends helped out, staying with one boy or the other at hospital while she went to lectures. Sa’id was one of 4 women in a class of 21 who graduated in 1996. She says that a streak of ambition kept her going.

“I wanted to be in a position where my opinion will matter, where I will be respected, Rohini Godbole, a physicist at the Indian Institute of Science in Bangalore. INDIA Rohini Godbole “I HAVE READ YOUR HUSBAND’S PAPERS — great work!” exclaimed a German physicist as he shook hands with Rohini Godbole. The seminal papers on particle physics, he assumed, had been written by a man.

But the author was Godbole herself — and the remark was one of many that she has deflected throughout her career. Based at the Indian Institute of Science in Bangalore, Godbole is one of her country’s few leading physicists. In 199 1, she discovered a way to describe the complex interplay of high-energy particles in linear col- liders 3 with Manuel Drees, now at the University of Bonn in Germany. Godbole is now one of the 16 members of the International Detector Advisory Group for the proposed International Linear Collider. She has received numerous awards and honours, and is an elected fellow of all three academies of science in India, a nation where about 37% of science PhD-holders, 20% of working scientists and less than 10% of professors are women.

Even today, says Anuradha Misra, head of physics at the University of Mumbai, “most promising women scientists in India, in spite of having immense potential, are not able to achieve as much due to societal and cultural constraints”. Godbole was born in Pune, the first scientist in a family rich in doctors and engineers. Her mother was a teacher, and her father said she could be whatever she wanted.

She won a coveted government scholarship to study physics, then did a master’s at the Indian Institute of Technology (IIT) in Mumbai and a PhD at Stony Brook University in New York. “Until I finished my PhD in physics, I never really thought that being a woman and doing science was somewhat of a special combination,” she says. That soon changed, as Godbole encountered discouragements on every score. When she joined the physics department at the Tata Institute of Fundamental Research (TIFR) in Mumbai for a postdoc in 1979, she found that there was a men’s toilet on every floor, but a women’s only on every alternate one — because there were so few women working there.

22 NATURE VOL 519 5 MARCH 2015 © 2015 Macmillan Publishers Limited. All rights reserved P. BALA SUBRAMANIAN I MUSTAPHA SHUAIBU HASSAN FEATURE NEWS Rabia Salihu Sa’id studies physics at Bayero University in Kano, Nigeria. Where my children could have the good things in life,” she says. She went on to get a PhD, then a job as a graduate assistant and eventually a permanent teaching and research post. She now studies the effect of dust aerosols on climate — she has shown, for example, how the constituents of Saharan dust aerosols alter the aerosols’ cooling or warming effects * 1 2 3. The challenges continue in her research: she has electricity for only four hours each day Said and other female scientists in Nigeria have found forms of support.

Some research- funding agencies give female applicants particu- lar encouragement or priority, and the Nigerian government has taken steps to reduce discrimi- nation and increase opportunities for women overall. Four years ago, Said and her colleagues formed Nigeria’s Association of Women Physi- cists, to encourage more women in the country into the field. At their first conference, it became clear that all the women had had similar experiences. The group agreed to try to improve rep- resentation of women through mentoring, prizes for female students, efforts to improve school physics teaching and a meeting twice a year.

Last month, at the annual meeting of the American Association for the Advancement of Science in San Jose, California, Sa’id received an Elsevier Foundation Award for Women in Science in the Developing World — she was one of five women honoured for work in physics and mathematics. “I have learnt that with high motivation and hard work, one can succeed,” she says. But women cannot progress without improvements in the country’s research infrastructure as a whole, she says.

“This is very important.” “I wanted tobeina position where my opinion will matter, where I will be respected. ” In some other physics departments, there were no female toilets at all. At the end of her postdoc, she was told by a senior professor that she should take up teaching in a women’s college. “There’s no expectation that you could be at the top, leading something, having a lab, directing PhD students,” she says. It was advice she chose to ignore, and soon she had a job as a lecturer at the University of Mumbai. The subtle — and not so subtle — messages have kept on coming, says Godbole.

Five years ago, she was elected a distinguished alumna of IIT, but women were still such a rarity in the group that the letter addressed her as c Dear Sir’. “These things could have put me down,” she says, but her energy carried her through. At Mumbai, she would usually lecture and work at the university until noon, then go to the TIFR some 30 kilo- metres away to continue her collaborations there. She would pause for dinner, work until 1 1 p.m., and then be ready to teach again the next day. The excitement of discovery was a driver too.

“Once in a while you figure out something that, until then, others have missed, and you feel suddenly like, £ Hey, I know something that others did not know!”’ she says. By 1994, she was a professor at the Indian Institute of Science. Meanwhile, Godbole’s family had been fretting that she was getting old and would never find a husband. Indian society expects women to put marriage and children first, and to weave their job around the family, says Vinita Sharma, former head of Science for Equity, Empowerment and Development, a Ministry of Science and Technology initiative that promotes science projects to help disadvantaged sections of society. Perceptions and attitudes are changing. In big cities, it is now consid- ered acceptable for women to study physics. The proportion of women starting a bachelor’s degree in science rose from 20% in 1970 to 40% in 2005, the most recent figures available.

Half of the students doing a physics master’s at the University of Mumbai are now women. In 2003, the Ministry of Science and Technology started a programme to encour- age female scientists to return to research after a career break. And in 2005, the government set up a National Task Force for Women in Sci- ence, which made recommendations, but has had limited impact. Shobhana Narasimhan, a physicist at the Jawaharlal Nehru Centre for Advanced Scientific Research in Bangalore, was on the taskforce. She says that there are two issues. First, the need to raise women’s aspirations — for this, leadership programmes can help, she says. (Godbole chairs a panel to study the issue of women in science, and has undertaken several initia- tives, such as mentoring aspiring female scientists.) The second is the need to change the attitudes of men, so that they consider women for leadership positions.

“This is hard!” says Narasimhan. “I think it helps for women to just c hang out’ with the guys and get accepted as one of them, but in conservative societies, this can often cause a lot of problems.” Godbole did get married, but never had children. “I didn’t see how I could juggle all the balls,” she says. “If there had been child care at institutions, it would have tipped the balance in terms of my decision not to have children. That’s the only regret I have.” She thinks future scientists should not be forced to make that choice, and she would like to see better child-care provision and extensions to postdoctoral contracts for women who have children during their positions, as is commonly done in Europe. Murenzi points to the significant cultural evolution that has opened up opportunities for women in places such as the United States and Europe: there is much more awareness of the obstacles than there once was, and greater efforts to minimize them.

“For the most part, developing nations have not come so far, so quickly,” he says. “Make no mistake, though — that evolution definitely is under way in many developing countries.” A few years ago, Godbole co-edited a book of biographies of almost 90 female scientists in India 4, in which she wrote that a female scientist needs a large dose of luck to have a successful career, a happy family and a happy marriage. Today, she says: “Whatever can be done to take the requirement of luck from this equation will be good.” ■ Katia Moskvitch is a science writer in London, and was an International Development Research Centre fellow at Nature. Fuwape, I., Fasunwon, S., Obiekezie, N. 1517, 132 (2013).

& Rashmibila, M. 20, 331-342 (2012). & Godbole, R. 67, 1189 (1991). & Ramaswamy, R.

(eds) LHavati’s Daughters (Indian Acad. 5 MARCH 2015 I VOL 519 NATURE 23 © 2015 Macmillan Publishers Limited. All rights reserved NEWS FEATURE - m o LU! — DC o CL CL ZD CO LU o LU _l c £ CD 350 300 250 200 150 100 50 0 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 Asia Pacific I Americas Europe, Middle East and Africa Chinese investment in solar power is driving down costs worldwide. For input and capital at international meetings such as the G20 summits. Finance flows to less developed and emerging economies will help to achieve the 2 °C goal.

Multilateral and national develop- ment banks must continue to expand their roles. Investment funds and financial instru- ments that reduce currency volatility, select the best projects and partially absorb unex- pected losses can increase financial flows. The Private Sector Facility of the Green Climate Fund — a component of the UN Framework Convention on Climate Change — will play an important part in leverag- ing private finance, increasing the size and impact of public climate finance. Even with the best of intentions, policy GREEN BONDS Banks, governments and companies have issued tens of billions of dollars’ worth of bonds to finance sustainable projects. Investors earn regular interest income and a further payment when the bond matures after a fixed period.

US$36.6 billion 2013 $11 billion 2012 $ 3.1 billion 2011 $ 1.2 billion 2010 $3.9 bil on 2009 $909 million 2008 $414 million 2007 $807 million missteps will occur. Financiers should see through short-term policy volatility by backing governments with clear low- carbon policy agendas and making them aware of the consequences of unpredict- able changes. Because markets cannot solve climate change alone, authorities such as the Financial Stability Board, which monitors the global financial system, must continue to provide direction. If appropriate policies are delivered, the capital shift that is under way will gather steam.

If not, investment will not be enough to meet the 2 °C global-warming limit. ■ Nathan Fabian is chief executive of the Investor Group on Climate Change Australia and New Zealand in Sydney, Australia. E-mail: nathanfahian@igcc.org.au 1. Global Trends In Clean Energy Investment (Bloomberg New Energy Finance, 2015).

United Nations Environment Programme. Aligning the Financial System with Sustainable Development: Pathways to Scale (UNEP, 2015). The Global Commission on the Economy and Climate. The New Climate Economy Report (The Global Commission on the Economy and Climate, 2014). International Energy Agency. Special Report: World Energy Investment Outlook (IEA, 2014).

Jr The coming climate crash’ The New York Times (21 June 2014). UK Law Commission.

Fiduciary Duties of Investment Intermediaries (UK Law Commission, 2014). Organisation for Economic Co-operation and Development. Mapping Channels to Mobilise Institutional Investment In Sustainable Energy (OECD, 2015).

The author declares competing financial interests: see go.nature.com/xmglaw for details. 5 MARCH 2015 VOL 519 NATURE 29 © 2015 Macmillan Publishers Limited. All rights reserved SPACE SCIENCE Beyond the heliopause Roger D. Launius savours a masterful account, by a veteran of interplanetary space science, of the Voyager probes’ mission to the giant planets.

Jupiter’s Great Red Spot, a massive stable storm photographed by Voyager 2 in 1979. P art memoir, part anecdotal history and part sermon on the delights of science, The Interstellar Age is a capti- vating read.

In it, planetary scientist Jim Bell presents the eventful story of NASA’s Voy- ager 1 and Voyager 2 missions to the edge of the Solar System and beyond. Bell, a veteran of many space-science missions, including several Mars probes, brings deft writing and an in-depth, nuanced understanding of big planetary-science efforts to this popular account. Voyager’s legendary status has been long assured, although The Interstellar Age will add to its cachet. Conceived in the 1960s and launched in the 1970s, the twin probes encountered the larger outer planets of the Solar System — Jupiter, Saturn, Uranus and Neptune — between the late 1970s and the late 1980s. Having gone far beyond their original remit, they now continue an inter- stellar mission at the edge of the Solar System. The probes are, in essence, c the little space- craft that could’. Bell writes about how, in the early 1960s, aerospace engineer Gary Flandro and other scientists realized that once every 176 years, Earth and the Solar System’s four giant planets gather on one side of the Sun.

This would enable close-up observation of the giants, in a planetary grand tour’. During the fly-by of each planet, a gravity assist — a slingshot effect, harnessing the planet’s movement and gravity — could increase the spacecraft’s velocity and reduce flight times. Bell describes the politics of the planning stage.

The four-planet scenario was possible, but NASA deemed it too expensive to build a spacecraft for an extended mission. Voyager was downgraded to a Jupiter-Saturn fly-by, but engineers designed as much longevity into the probes as the US$875-million budget would allow. NASA launched Voyager 2 on 20 August 1977, and Voyager 1 followed on a faster, shorter trajectory on 5 September. Bell, who hung out with the science team as an undergraduate at the California Insti- tute of Technology in Pasadena, describes how the craft achieved their objectives — and then some.

Voyager 1 was, for example, pro- grammed for a close encounter with Saturn’s moon Titan, during which it revealed a com- plex world with an atmosphere, thick clouds and water ice. It showed that Titan was ripe for scientific investigation, paving the way for the sustained investigations of the Huygens- Cassini mission at the dawn of this century. But this fly-by deflected Voyager 1 out of the Solar System’s elliptical plane; unable to con- tinue on to Uranus and Neptune, the craft’s planetary mission ended. Voyager 2 continued on to the two outer- most giant planets. Bell reports how, as the probes flew, controllers constantly repro- grammed the on-board computers, which had only about 5,000 words’ worth of mem- ory each, to take advantage of scientific opportunities.

Successfully capturing data was hugely taxing, but mission engineers and scientists made it work. The probes explored the giant planets’ systems of rings and magnetic fields, find- ing previously unknown geological activity on Io, a moon of Jupiter with numerous vol- canic features. The Voyagers also explored a total of 48 moons around the gas giants.

They sent back more than 100,000 images of the planets, rings and satellites, and took magnetic measure- ments, chemical spectra and radiation readings. The infor- mation revolutionized Solar System science, helping to resolve key questions about how it was formed and rais- ing intriguing new ideas such as the pos- sibilities of life beyond Earth. Bell is at his best in telling the human I i r£L Ufi '•'E*.

Hi, w The Interstellar Age: Inside the Forty-Year Voyager Mission JIM BELL Dutton: 2015. 30 NATURE VOL 519 5 MARCH 2015 © 2015 Macmillan Publishers Limited. All rights reserved NASA/S PL JOELSAGET/AFP/GETTY NASA/JPL/SPL BOOKS & ARTS COMMENT The identical Voyager probes launched in 1977 and are still travelling. Stories of discovery, excitement and public engagement. He describes the extension of the Voyager mission to the heliopause, where the Sun’s energy is overpowered by interstellar forces.

Ed Stone, who has been chief scientist for Voyager since its inception, evinced the excitement of a self-confessed non-party animal. “I can still remember taking the data home every night, and putting the plots on the refrig- erator,” he tells Bell. “I couldn’t stop think- ing about them, wondering what would happen next.” Voyager 1 is now more than 130 astro- nomical units ( au) from the Sun ( 1 au is the distance between the Sun and Earth, around 150 million kilometres), and Voyager 2 is at more than 107 au. They continue to take readings of the heliopause. Thanks to astronomer Carl Sagan, one of Bell’s heroes, both probes contain messages from Earth: gold-plated cop- per phonograph records encoded with 115 images of scenes from Earth, audio greetings in 55 languages, and 90 minutes of music from Bach to Chuck Berry, along with playing instructions. This message in a bottle is one of the mission’s best- known attributes, and Bell explains well its publicity value and how it represents a feel-good sentiment about the possibility of encountering interstellar life. The Voyagers demonstrate the remark- able advances in robotic space explora- tion over the past almost 40 years, and suggest that subsequent missions may yield even more exciting results.

Such follow-ups as the Galileo mission to Jupi- ter, Huygens-Cassini to Saturn and New Horizons to the Kuiper belt including Pluto may herald even more ambitious missions — to Titan, for instance, where they might sail on a hydrocarbon sea, or to Jupiter’s moon Europa, to explore an ice-covered liquid-water ocean that has the potential to harbour life. I believe that NASA’s greatest achieve- ment is the Apollo Moon programme. The odyssey of the Voyagers certainly vies for second place.

Bell appropriately quotes historian Stephen Pyne: “The Voyagers were special when they launched. They have become more so thanks to their lon- gevity, the breadth of their discoveries, the cultural payload they carried, and the sheer audacity of their quest.” ■ Roger D.

Launius is associate director for collections and curatorial affairs at the Smithsonian Institutions National Air and Space Museum in Washington DC. E-mail: launiusr@si.edu MATHEMATICS Groping in the dark for glimpses of beauty Amir Alexander relishes two accomplished accounts of the life mathematical. O ne evening in 2009, French math- ematician Cedric Villani stepped into his children’s room.

He locked the door, turned off the light and began to pace, pondering the statistical properties of plasma. A few metres away, his wife, Claire, was in the kitchen, cooking dinner for the family.

The contrast, Villani concedes in his engaging Birth of a Theorem, was “a bit much”, yet immediately after dinner he returned to the dark room to grapple for hours with his elusive proof. Anyone reading that anecdote will feel sympathy for Claire as she tries to preserve family normality.

Anyone who has seri- ously engaged with mathematics will also understand her husband. Perhaps more than any other field, mathematics pulls the practitioner away from the normal’ world of things and people into a strange alternate universe, in which we catch glimpses of beauty and coherence, but spend most of our time groping in the dark. In Birth of a Theo- rem, Villani offers one way of straddling that divide; in Mathematics Without Apologies, fellow mathematician Michael Harris pre- sents a very different one.

Together, they provide an unmatched perspective on life in this “problematic vocation” by two of its leading practitioners. Birth of a Theorem is the story of Villani’s quest to give a full mathematical account of Landau damping. Whereas gas becomes increasingly disordered over time as entropy increases, plasma spontaneously stabilizes, with no increase in entropy.

Soviet physicist Lev Landau was the first to mathematically describe this improbable phenomenon, but he used a simplified model that left many unconvinced. Working closely for several years with mathematician Clement Mohout, Villani succeeded, and he was awarded a Fields Medal in 2010. Villani’s quest takes him across the world, from Lyons, France, to Princeton, back to Paris and on to Hyderabad in India. At every stop, he talks to local mathematicians, demonstrating that, for all its abstractness, mathematics can be an intensely social activ- ity.

The book is sprin- kled with brief, telling ONATURE.COM For more on science in culture, see: nature.com/ booksandarts Birth of a Theorem: A Mathematical Adventure CEDRIC VILLANI Bod ley Head/Faber and Faber: 2015. Mathematics Without Apologies: Portrait of a Problematic Vocation MICHAEL HARRIS Princeton Univ. Press: 201 5. Cedric Villani studies the maths of plasmas.

Portrayals of mathematicians and physicists past and present. The grumpy, grey-haired Etienne Ghys of Lyons and Chinese expat Alice Chang of Princeton alternate with the autocratic Lev Landau in 1960s Moscow and the ever-present shadow of Albert Einstein at the Institute for Advanced Study in Prince- ton. Much of Villani’s e-mail correspondence with Mohout is reproduced, chronicling moments of triumph and despair. Charismatic and flamboyantly dressed, Villani is the opposite of the mathematical hermit’ and annoyed by the stereotype.

He attends a recital by one of his children, joins his family at the American Museum of Natu- ral History in New York and travels a long way to attend a concert by rock band Tetes Raides. Yet he studies the mathematics of galaxy for- mation during the recital, works out a step in his proof on the bus from the museum, and explains his research to a stranger who drives him back from the concert. The mathematical life, in his telling, is a delicate dance between the demands of the Teal’ world and the VOL 519 NATURE 31 © 2015 Macmillan Publishers Limited. All rights reserved 5 MARCH 2015 COMMENT BOOKS & ARTS allure of the mathematical one. If Birth of a Theorem is the personal record of a single-minded quest, Mathe- matics Without Apologies is a kaleidoscope of philosophical, sociological, historical and literary perspectives on what math- ematicians do, and why. Do they pursue their work for the public good? Harris dismisses that as a pose, useful for grant applications and little else.

Is it the abso- lute truth of mathematical demonstra- tions that drives the field? That, Harris contends, is a conceit of philosophers: practising mathematicians seek insight, not certainty. What about the lauded beauty of mathematics?

Perhaps, Harris concedes, but when mathematicians talk about beauty, what they mean is pleasure. A 2012 sociological survey found that 91% of pure mathematicians cited it as a key attribute of the field. Mathematicians, Harris concludes, do what they do because of the enormous pleasure it brings them. Pleasure is not an explanation likely to satisfy funding agencies.

Yet Harris makes no apologies. He is concerned that the field has made a Faustian bar- gain with the institutions that provide the material conditions for mathematical research. Leading mathematics depart- ments have trained an army of quantita- tive analysts, or quants, to implement the algorithms that govern financial trading practices. The impersonal, unchallenge- able equations of higher mathematics, he worries, contribute to a moral vacuum at the heart of high finance.

Harris’s insider view reveals a com- munity in which each mathematician is placed in an informal but strict hierarchy, depending on acknowledged brilliance and accomplishments. He takes a play- ful detour, arguing that each of US writer Thomas Pynchon’s non-linear’ novels is organized around a different conic sec- tion, such as a parabola. Throughout the book, he verbally spars with an imaginary “performing artist” while trying to explain the mysteries of number theory. But, like Villani, Harris returns repeat- edly to the chasm between the human world and the mathematical one — a ten- sion that in his own life has proved fruit- ful. Stuck in a professional cul-de-sac in the 1990s, Harris experienced a revelation: a dream showed him a new mathematical path, which led to his ascent up the mathe- matical hierarchy and transformed his life. For him as for Villani, mathematical insight at its deepest core remains an irreducible personal experience.

■ Amir Alexander is the author, most recently, o/Infinitesimal. He teaches at the University of California, Los Angeles, e-mail: amiralex@ucla.edu 32 NATURE VOL 519 SOCIAL SCIENCE Aid’s inconvenient truth Erin Bohensky applauds a documentary revealing how disaster relief can have disastrous impacts. A t the start of Raphael Barth’s provoca- tive documentary Aftermath, a bot- tle of Coca-Cola lands on a pristine beach. The image calls to mind the satirical 1980 film The Gods Must Be Crazy, in which the lives of Kalahari Desert tribal peoples are changed irreversibly by moderniza- tion. Barth’s is the true story of how foreign aid delivered to inhabitants of the Nicobar Islands after the 2004 Indian Ocean tsunami became a second disaster. Barth’s film focuses on social ecologist Simron Singh and his work with these indig- enous peoples.

In setting out to help them, Singh grapples with two questions: why is aid so dysfunctional, and how can science help people in crisis? Singh first visited the islands in 1999 to research Nicobarese culture, and befriended many in the community. After the tsunami, they asked him for help. Singh mobilized funding from the Austrian Science Fund to support rehabilitation research.

In the film, he — with community spokesperson Prince Rasheed “Even well- directed intervention is no substitutefor empowerment. ” Yusoof and local reporter Denis Giles — watches aid pour in from hundreds of non-governmen- tal organizations (NGOs). In effect, the tsunami engineers the perfect social experiment, revealing what happens when cash and unneeded commodities are fun- nelled to a remote indigenous community. There was “no way back”, Singh admits.

The donations, Barth shows, are mis- matched to needs and context. The com- munity wants tools; donors bring blankets. Houses and schools rebuilt with aid are ill- ventilated “boiling chambers”. A government initiative provides European -style dwellings housing just five or six people, fragment- ing the large joint family groups traditional among the Nicobarese. “Who is helping whom?” Singh asks. “Are the victims helping the organizations to reproduce themselves?” How can the messy problem of ineffec- tive aid be fixed? Development analyst Ben Ramalingam has argued that we must under- stand development as a complex system to address underlying causes rather than treat symptoms.

Aftermath shows Singh and col- leagues in Vienna creating the Sustainable Indigenous Futures (SIF) fund in 2005, to provide financial aid directly to the com- munity. As they soon learn, however, even well-directed interven- tion is no substitute for empowerment. Nom- inated community members struggle to abide by NGO norms of accountability.

“A Nicobarese can- not become a project officer in ten days,” Yusoof concedes. The community shuns Singh when the SIF stops sending money. In 2009, Singh and the SIF establish a partnership with a local NGO, the Tata Institute of Social Sciences, to rein- state resource-based livelihoods such as fish- ing in the islands. Is the global aid enterprise learning from its mistakes? Extreme events can be catalysts for change.

One young Nicobarese man leaves to pursue a higher degree, noting how the tsunami has shaped his aspirations. Yusoof is building a community tourist resort to generate income locally. Through such proactivity, resilience is built. Finally, we see Singh, meticulously sort- ing slides, promising to document it all for the Nicobarese.

But he questions the current paradigm of aid based on Western capitalist values. He even asks whether people in crisis need assistance at all.

Scientists, he proposes, can help most by bringing together scientific and local ways of thinking to guide NGOs’ actions on the ground. Aftermath is a gritty, honest picture of two communities: the Nicobarese and aid agen- cies. Raw moments such as a ceremonial pig butchering, or a glimpse of the ethical and administrative conflicts that can trap development agencies in operational grid- lock, are delivered unflinchingly.

Ultimately, the Nicobarese have hope. “The aid has stopped,” Yusoof concludes.“Now the real normal life starts, and we are happy.” ■ Erin Bohensky is a senior research scientist in livelihoods and adaptive development at the Commonwealth Scientific and Industrial Research Organisation in Townsville, Australia. E-mail: erin.

Bohensky@csiro.au Aftermath: The Second Flood DIRECTOR: RAPHAEL BARTH Golden Girls/FI I mtank/ Twopair/Tata Institute of Social Sciences/ ORF: 2014. 5 MARCH 2015 © 2015 Macmillan Publishers Limited. All rights reserved Correspondence Target for ecosystem repair is impractical The Convention on Biological Diversity (CBD) agreed in 2010 to restore “at least 15 per cent of degraded ecosystems” by 2020 (www.cbd.int/sp/targets).

In Finland’s experience, this target is unrealistic. Ecosystem destruction is measured according to the expanse and degree of degradation. Consequently, under the CBD agreement, damage to an ecosystems condition needs to be reduced by 15% over an entire area of degraded landscape or, for example, by 33% in a randomly selected 45% of that area to attain the same reduction. There are considerable challenges in achieving this reduction: heavy restoration measures must be completed across large areas and in a short time, while compensating for ongoing degradation elsewhere. Finland’s forests cover roughly 15 million hectares, 95% of which have been degraded by forestry operations. To meet the CBD target, the country would need to reduce degradation by 33% in more than 100,000 hectares each month until 2020.

It has already taken Finland almost 30 years to restore some 30,000 hectares of forest (see Table 2.5 at go.nature.com/pajic9) — one-thousandth of the CBD’s monthly requirement. There is a danger that parties to the CBD will ignore the target because of its sheer impracticality. Kotiaho* University of Jyvaskyla, Finland. Janne.kotiaho@jyu.fi *On behalf of 7 correspondents (see go. Nature, com/ dcyoft for full list). Sports doping vastly underestimated Roger Pielke Jr suggests that doping prevalence can be estimated by drug testing of athletes ( Nature 517, 529; 2015).

I contend that this method is flawed: as the autobiographies of some athletes attest, regular dopers have a track record of avoiding testing positive. To estimate doping’s true prevalence, two procedures that circumvent inherent weaknesses in simple counts of positive test results are useful. First, Bayesian inference methods can be used to compare two distributions of biological parameters affected by doping: one distribution among sampled athletes and the other in a suitable reference population, allowing the number of manipulated samples to be estimated (R-E. 57, 762-769; 2011). A major advantage of this population-level analysis is that it can recognize abnormalities even when dopers’ values remain within the normal’ range.

Second, specially tailored questionnaires allow athletes to give honest answers to doping questions under cover of anonymity (W. Pitsch et al. 4, 89-102; 2007).

The questionnaires are based on the randomized response technique and are used by social scientists to study illegal and deviant behaviours. A combination of these approaches estimates that 14-39% of elite athletes have intentionally doped (see O. De Hon et al. 45, 57-69; 2015). This contrasts markedly with the 2% of samples designated as suspect in the World Anti-Doping Agency’s published statistics.

Simon Evans Uppsala University, Uppsala, Sweden, simon. Uu.se A marine biologist’s remarkable legacy We write to dispel some myths in characterizations of the marine biologist Ed Ricketts, who died in 1948 (see, for example, A. Hirsh Nature 516, 326-328; 2014). Far from working in isolation, Ricketts interacted and corresponded with Torsten Gislen, George MacGinitie and Willis Hewatt, who all studied intertidal creatures. He did the same with scientists at the Smithsonian Institution in Washington DC and those at US and foreign universities. Never having taken a university degree, he was eager to tap into their expertise and to contribute to the international body of knowledge. Hirsh’s observation that Ricketts’ book, Between Pacific Tides, was revolutionary because “it categorizes animals according to habitat, not phylum or family” is not the whole story.

Ricketts’ years of data from tidepool observations and collections resulted in a complex card- indexing and cross-referencing system that allowed him to build conclusions about species and their habitats and animal communities. As a result, his ecological data sets are still among the most robust ever to have been assembled. Steven Albert, Mary Albert Pacific Grove, California, USA.

Don Kohrs Hopkins Marine Station of Stanford University, Pacific Grove, California, USA. Net German initiative opens up animal data Reliable and transparent data are essential to discussions of suffering in animal experimentation. A new initiative in Germany provides user-friendly public information about authorized animal- research projects. The European directive to protect laboratory animals (2010/63/EU) requires researchers to provide an anonymous, non-technical summary of a proposed project, stating its purpose and potential benefits. The summaries also detail the number and types of animal to be used, the predicted harm to the animals and the evidence of compliance with the C 3R’ principles (see go.nature. The severity of 5 MARCH © 2015 Macmillan Publishers Limited.

All rights reserved animal suffering and the likely human benefits are central to the approval process. Germany’s Federal Institute for Risk Assessment (BfR) has created a freely accessible, searchable website of these summaries to provide the public with clear insight into animal experiments (see www. Summaries are available to all EU member states, which could all set up similar open-access databases. The summaries provide a unique channel for scientists to communicate their work to the public. They are a milestone in attempts to safeguard transparency in animal research, which is particularly controversial in the case of non - human primates. Gilbert Schonfelder* BfR, Berlin; and Charite — University Medicine Berlin, Germany.

Gilbert.schoenfelder@bfr.bund.de *On behalf of 4 correspondents (see go.nature com/ ebzmxo for full list). Glass-blowing’s Nobel moment One of the most striking contributions of glass-blowing to research (see Nature 517, 542-546; 2015) is the creation of 1 1,146 hemispherical photomultipliers in the neutrino detector used by Nobel laureate Masatoshi Koshiba. Their 50-centimetre diameters are a phenomenal achievement that called for great skill, strength and exceptional lung capacity. Koshiba was awarded the Nobel Prize in Physics in 2002 for the detection of cosmic neutrinos at the Kamioka Observatory in Hida, Japan. He acknowledged the glass-blowers of the Hamamatsu Photonics firm in his Nobel lecture, saying that the 50-cm-diameter photomultipliers “were the essential ingredient of the Kamioka experiments”. Min-Liang Wong National Chung-Hsing University, Taichung, Taiwan.

Tw 2015 VOL 519 NATURE 33 COMMENT OBITUARY Carl Djerassi (1923-2015) Chemist, writer and contraceptive-pill pioneer. F ew scientists have changed society as much as Carl Djerassi did. By chemically synthesizing a steroid mimic of the hormone pro- gesterone, Djerassi paved the way for the oral contraceptive pill, allowing women for the first time reliably to take control of their own reproduc- tive choices. Djerassi’s conviction that ‘the pill’ made the sexual liberaliza- tion of the 1960s possible is widely shared, and chemical control of the fertility cycle was a key ingredient in subsequent advances in reproductive technologies, beginning with in vitro fertilization (IVF) in the late 1960s. This alone would have warranted Djerassi’s acclaim as a scientist.

But he also made important contributions to the synthesis of antihistamines and other natural products, pest control using hormone derivatives, mass spectrometry and computer- ized methods for the determination of complex molecular structures. He spoke and wrote extensively about the role of science in society and the ethical dilemmas it brings up. He also wrote fiction and plays.

Calling himself an “intellectual polygamist”, he showed how science could and should make its presence felt outside the laboratory. Djerassi, who died on 30 January aged 91, was born to Jewish parents in Vienna in 1923. His parents separated in the late 1930s, and in 1939, following the Nazi annexation of Austria, he left with his mother for the United States. His PhD at the University of Wisconsin-Madison concerned the chemical transformation of human male and female sex hormones. In 1942, he joined the pharmaceutical com- pany Ciba in New Jersey, where he took out a patent on one of the first synthetic anti- histamines.

Djerassi started working at the small pharmaceutical company Syntex in Mexico City in 1949. There he established how to synthesize cortisone from a natural prod- uct derived from the Mexican yam. He then found that the same starting com- pound could yield norethisterone, a mimic of progesterone, which controls the female menstrual cycle.

The discovery was devel- oped in the late 1950s by biologist Gregory Pincus and gynaecologist John Rock, both of whom had conducted early work on IVF, to create a commercial contraceptive pill. Such pills were first approved in the United States in 1960.

The previous year, Djerassi had joined the chemistry department at Stanford University in California, where he stayed until he retired in 2002. His connection with the Syntex Corporation, of which he became director in 1960, and with the insect-control company Zoecon, which he founded in 1968, made him rich. Numer- ous awards followed. Whereas many would have rested on their laurels, in his seventh decade Djerassi began a career as a writer and playwright, starting with the novel Cantors Dilemma (1989). He styled himself an “intellectual smuggler”, bringing science, under the guise of entertainment (which he called science-in-fiction), to audiences who might normally have recoiled from it. His most successful play, Oxygen (2001), written with chemistry Nobel laureate Roald Hoffmann, explored the delib- erations of a Nobel committee deciding whether to award a retrospective prize for the element’s discovery to Antoine Lavoisier, Carl Wilhelm Scheele or Joseph Priestley. Like several of Djerassi’s other works, it examined how scientific credit is awarded and the personal dynamics of research.

The work of which he was most proud, however, was Foreplay (2011), which explored the sexual intrigues between a quartet of early - twentieth-century German intellec- tuals. His investment in the arts was profound and literal. Motivated by the suicide of his artist daughter Pamela in 1978, he founded an artists’ colony in Woodside, California, which has hosted more than 2,000 residencies. Even when Carl was forced to use a walking stick, it was easy to imagine that he had simply forbidden old age to plague him. “I had regaled my wife [Stanford professor of English Diane Middlebrook] for years with macho pride that I intended. To become the first non-retired centenarian profes- sor at Stanford,” he wrote. “I always allowed the barest of smiles to cross my face whenever I bragged in that fashion.” That was Djerassi all over: proud to the point of arrogance, but at the same time mocking his own bombast.

No one who knew Carl would deny that there were prickly aspects to his charac- ter. He did not aspire to modesty and was quick to perceive slights. But his determi- nation to grasp and grapple with what it means to be human in the modern age was admirable. His passion for the communi- cation of scientific ideas was coupled with a profound aesthetic sensibility, as shown by his deep appreciation for the artist Paul Klee, several of whose works he owned. Incredulity that Carl was never awarded a Nobel Prize was widely shared among his peers, and quite possibly by Carl himself. And his ambitions in writing and commu- nication were not always welcomed even in his own institution, where he was once told that “in recent years your interests have been far removed from those most highly valued by your department”. Hopefully academia is more ready now to recognize the value, indeed necessity, of professional scientists who turn their ener- gies to public engagement and to embedding science in its social context.

Few have tried harder to do that than Carl Djerassi. ■ Philip Ball is a science writer based in London. Ball@b tinier net. Com 34 NATURE VOL 519 5 MARCH 2015 © 2015 Macmillan Publishers Limited. All rights reserved BETTMANN/CORBIS NEWS & VIEWS For News & Views online, go to nature.com/newsandviews Tied down by its own receptor An engineered protein that binds to the envelope of HIV viruses protects monkeys against infection with a simian-human virus that causes AIDS. This gene-therapy approach might provide an alternative to elusive HIV vaccines.

See Letter p.87 a Envelope b c protein Figure 1 1 Vaccination versus gene therapy, a, HIV infection begins with the virus’s envelope protein binding to CD4 and CCR5 molecules on the surface of T cells. Most current strategies aimed at conferring protection against HIV focus on vaccines that are designed to prevent this binding by producing antibodies that bind to structures shared by the envelope of many HIV strains. However, antibodies bind only to small sections of the envelope, and the virus can evolve to shield these regions from antibody binding, b, An alternative approach proposed to stop virus binding to host cells is to use artificial constructs of human CD4 attached to immunoglobulin molecules. These CD4-Ig constructs will bind many viral strains, but they may expose the CCR5 binding site on the envelope protein and thus actually facilitate binding of the virus to CCR5 on the host cell, c, Gardner et al 2 present an alternative construct, eCD4-Ig, which contains both CD4 and a mimetic of CCR5 and therefore blocks both points of viral binding. HAIGWOOD T he past 30 years have been marked by a long and discouraging search for an effective HIV vaccine. In 2009, the ‘Thai trial’ of the candidate vaccine RV 144 was the first to demonstrate any success, measuring a 31.2% reduction in the rate of infection, although efficacy decreased over the first year after vaccination 1. The difficulty in develop- ing a more effective vaccine has forced inves- tigators to explore problems that are posed by other intractable pathogens, including persistence in the host, a high degree of vari- ability of certain regions, masking of common regions, and pathogen-induced inhibition of host immunity.

But on page 87 of this issue, Gardner et al. 2 describe research suggesting that protection against HIV infection may be achievable through a gene-therapy approach, rather than by relying on eliciting protective immune responses by vaccination. The trimeric envelope protein that is found on the surface of the viral particle of nearly all HIV strains binds directly to the CD4 recep- tor protein on the surface of many human immune cells, such as T cells and macrophages. This binding event causes a major shift in the envelope conformation, allowing the virus to bind to other co- receptors and enter the cell.

It has been known since 1984 that CD4 is the receptor for HIV 3,4, and various forms of stabi- lized CD4 tethered to human immunoglobulin molecules (CD4-Ig) have been proposed and tested as potential therapeutics — the idea was that viral binding to these constructs would neutralize’ the virus by preventing it binding to and entering cells. But this approach failed. Gardner and colleagues’ findings provide the first logical explanation for this failure, and suggest an elegant way of using human CD4 derivatives to prevent infection.

The researchers engineered CD4 by fusing it with a mimetic of the amino terminus of CCR5, the host-cell co-receptor used by most HIV-1 strains during infection and disease progression. The CCR5 terminus has two sul- fated tyrosine amino-acid residues that bind to the HIV envelope and facilitate viral entry 5, so the peptide mimetic is a sulfopeptide. The mimetic was based on an antibody that binds to the CCR5 binding site of the viral envelope; 36 NATURE VOL 519 5 MARCH 2015 the authors modified and positioned it in the CD4-Ig construct for maximum activity and fit. This synthetic compound, named eCD4-Ig, has potent and broad neutralizing activ- ity against all HIV isolates tested, including viral strains that are typically thought of as highly resistant to neutralization. It achieved these effects at lower concentrations than required when using the neutralizing mono- clonal antibodies (NmAbs) that arise during the immune responses of some patients to HIV, and which are currently a major focus of attempts to develop HIV vaccines that pre- vent infection, rather than modulate viraemia once infection has occurred 6. Furthermore, the construct was more effective than previous CD4-Ig constructs or the NmAb bl2 at indu- cing immune killing of HIV- infected cells — a process known as antibody-dependent cellular cytotoxicity, which functions in concert with viral neutralization.

Gardner et al. Went on to show that the eCD4-Ig construct imparted resistance to HIV-1 when infused into mice that model human HIV infections. As a further test of in vivo activity, the authors treated monkeys with an adenovirus-associated virus (AAV) © 2015 Macmillan Publishers Limited. All rights reserved that expressed the gene encoding a rhesus macaque version of the eCD4-Ig construct and with a separate AAV vector expressing a rhesus macaque enzyme to promote efficient sulfation. This gene-therapy vector allows con- tinuous expression of the desired proteins in host cells by integrating into the host genome. The animals expressed the transgene stably, although at different levels, and all were fully protected against repeated challenge with increasing doses of SHIV (a virus combining parts of the simian immunodeficiency virus (SIV) and HIV genomes). This protection was sustained for as long as 34 weeks after AAV transduction, and was achieved despite the monkeys receiving the virus intravenously, which is considered the infection route that provides the most stringent test of protection.

These findings improve on an earlier test of the AAV transduction system to express a NmAb specific for SIV in monkeys 7, in which only a subset of monkeys that expressed the transgene were protected from SIV challenge. Why did Gardner and colleagues’ construct work? In a nutshell, it all comes down to the way that eCD4-Ig binds to the virus (Fig. Human NmAbs that are able to neutralize a RESEARCH NEWS & VIEWS broad range of HIV- 1 strains do so by binding with very high affinity to shared viral structures (epitopes) that have precise but relatively small footprints. However, HIV has a variety of tricks to shield these shared epitopes from the immune system, although some infected individuals — referred to as elite neutralizers — do produce NmAbs of this sort. By contrast, CD4 binds to the envelope of all HIV- 1 strains, albeit at lower affinity than these super potent’ NmAbs.

However, CD4 binding leads to a conformational change in the envelope that exposes the CCR5 binding site, thus potentially promoting HIV-1 infec- tion in CCR5-expressing cells 8. The modi- fications introduced by Gardner et al.

Into their eCD4-Ig construct seem to overcome this problem by preventing the engagement of envelope proteins with CCR5, while at the same time engaging multiple parts of the viral envelope, thereby increasing the binding power of their construct. The study raises several questions and a few caveats. First, the modified protein is not natural and required the co- expression of an enzyme to perform the efficient addition of the sulfate moiety onto tyrosine residues. Second, the sample size of the monkey studies was quite small, and larger experiments in non-human primates are warranted. Furthermore, the intra- venous challenge route, although rigorous, is not representative of the vast number of HIV- 1 exposures worldwide, and it remains to be seen how expression of eCD4-Ig would affect virus challenges at mucosal sites, which better mimic natural routes of infection.

It is also not yet clear whether the construct needs to be expressed close to the challenge sites. This, too, could be tested in non-human primate models. Another major question rests in understand- ing the safety of eCD4-Ig in humans.

Immune responses against the protein were elicited in the monkeys, albeit less strongly than against human NmAbs, and such responses could undermine its efficacy. But perhaps the great- est caveat to clinical application of the con- struct is how it, or future derivatives, will be used in humans. Such a complex molecule is unlikely to be administered repeatedly to those at risk of HIV infection, although that might be considered if it could be applied topically. The risks of expressing the construct as a transgene, in a similar manner to Gardner and colleagues’ monkey experiments, are not known, and this approach would require careful and stepwise clinical safety testing. However, in the absence of a vaccine that can elicit broadly protective immunity and prevent infection, and given the lack of major breakthroughs on the horizon to provide one, the idea of conferring potent, sustained vaccine-like protection against HIV infection through gene therapy is certainly worth strong consideration. Haigwood is in the Division ofPathobiology & Immunology, Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, Oregon 97006, USA.

E-mail: haigwoon@ohsu.edu 1. Rerks-Ngarm, S. 361, 2209-2220 (2009). BARNARD T he ability to move when and where we want is fundamental to our way of life, and our capacity for directing the natural motion of other objects and materials is essential for a range of technologies, from medicine to power generation. Although the same principles apply at the nanometre scale, miniature machines based on conventional macro-scale mechanisms have suffered from various problems, including lack of direc- tional control, crippling frictional forces and permanent adhesion to adjacent components through strong chemical bonding. Writing in Physical Review Letters, Chang et al. 1 introduce 3.

Dalgleish, A. Nature 312, 763-767 (1984). Klatzmann, D. Nature 312, 767-768 (1984). Cell 96, 667-676 (1999). Nature 502, 100-104 (2013). 15, 901-906 (2009).

61, 135-152 (2010). This article was published online on 18 February 2015. A new way of moving nanoscale materials that overcomes some of these challenges, and that does not need an external power source to drive it. Being able to control the motion of nano- materials would be extremely useful for processes that require the delivery of mol- ecules and other nanoscale objects, and for the functioning of nanodevices such as energy- conversion systems. With specific applica- tions in mind, several techniques for moving various nanostructures have been proposed, using electrical currents 2 (or charge 3 ), selective heating 4 or complicated chemical reactions 5. But none of these methods is intrinsic — the nanostructures do not move spontaneously, Figure 1 1 Stiffness-guided motion. Chang and colleagues’ computer simulations 1 reveal that, when a short graphene nano-flake (black) is placed on a graphene substrate containing a stiffness gradient, it spontaneously accelerates away from the soft (red) regions and towards more-rigid (blue) regions, without an external driving force.

The authors attribute this behaviour to an inverse relationship between the substrates stiffness and the interaction between the substrate and the flake (the van der Waals potential energy), which suggests that the velocity can be tuned. (Figure adapted from ref. Nature 519, 87-91 (2015).

MATERIALS SCIENCE Nanoscale locomotion without fuel Computer simulations have revealed a mechanism by which nanostructures of the material graphene can be driven in one direction by controlling the stiffness of the underlying substrate. 5 MARCH 2015 VOL 519 NATURE 37 © 2015 Macmillan Publishers Limited. All rights reserved RESEARCH NEWS & VIEWS and each technique requires an energy source to sustain the motion.

Furthermore, all the techniques can potentially damage the mater- ials, which reduces the repeatability of each process. This is a problem, because viable nanotechnology must be reliable, reusable and cost-effective to run. To find a method that fulfils these requirements and that has no need for exter- nal intervention, Chang et al. Set up a series of virtual experiments using computer simula- tions. This approach offers some advantages over real-world experiments: one can be sure that the materials are free of defects and impu- rities, and that they are electrically, thermally and chemically isolated.

Such isolation is par- ticularly important when seeking intrinsic phenomena. In their simulations, the authors first laid a nano-flake of graphene on top of a continu- ous graphene substrate, taking care to ensure that the lattices were not aligned.

Graphene is a hexagonal lattice of carbon atoms, only one atomic layer thick, but its structure at the highly reactive edges varies depending on how the edges have been cut * 1 2 3 4 5 6. In the simulations, the flake was rotated by 30° with respect to the substrate, so that its edges did not line up with the lattice beneath. This reduced the risk of the flake becoming permanently attached to the substrate as a result of strong covalent bonding between the edges of the flake and the edges of the substrate. Once it was in position, the authors made no further changes to the flake, but applied a stiffness gradient to the substrate, ranging from 0.801 to 4.005 newtons per metre along one direction. When the molecular- dynamics simulation was engaged, the nano -flake moved spontaneously — from a standing start — from the soft side to the hard side of the substrate (Fig. Then, when it reached the end of the substrate, it rebounded because of a retraction force that pulled it back. Similar forces have been observed to pull extruded cores of multi- walled nanotubes back into the nanotubes 7.

Another advantage of computer simulations is that it allows animations of modelled pro- cesses to be made. In the present case, the overall motion is dramatically displayed in an anima- tion provided with the paper s supplementary material. One can see that the graphene flake accelerates as it approaches the hard side of the substrate, and decelerates as it rebounds towards the soft side. This is clear evidence that the stiff side is energetically preferred.

Such stiffness-guided directional motion (termed durotaxis) was first observed in liv- ing cells, which also prefer rigidity 8 9. Although the biological mechanism for durotaxis in cells remains a mystery, it has another similar- ity to the nanodurotaxis observed by Chang and co-workers in their simulated system: in both cases, weak van der Waals interactions are present, and in the latter case they were found to be crucial.

To prove this, the authors systematically repeated their virtual experiments under different simulation conditions, varying temperatures, stiffness gradients and stiffness configurations. The results unambiguously showed that the strength of the effective van der Waals potential — the interaction between the flake and the substrate — was inversely proportional to the stiffness.

Lower potential energies are always more stable than higher ones, so this explains why the flake moves towards a rigid spot on the substrate: by doing so, it adopts a thermodynamically preferred state. At this stage, it is unclear whether per- turbations to the system could be devised to reverse the motion, driving the flake back to soft regions. Chang and colleagues’ findings could have great potential in nanodevices, in part because the observed motion is conveni- ently unidirectional, but also because the underlying forces fall within a useful and technologically accessible range. The driving force for the nanoscale locomotion is about 320 kilopascals per square nanometre for a 6-nm-wide nanoflake on a stiffness gradient of0.801-2.403Nm _1.

This is not too dissimilar from the forces in biological systems, such as the traction force per unit area exerted by a living cell on a substrate 8,9 and the driving force generated in a protein biomotor 10. The challenge now is to fabricate graphene substrates that contain deliberate patterns of soft and hard regions, so that the experiments NEUROSCIENCE SACHIN PATEL & ROGER D. CONE A ccording to data gathered by the United Nations 1, 177 million people around the globe use marijuana. So some of you might be familiar with the munchies — that inexplicable drive to eat, stimulated by the active ingredients of mari- juana, the cannabinoids. This connection has already led to the development of dronabinol, a synthetic version of the natural cannabinoid A-9-tetrahydrocannabinol, as a treatment for the metabolic disorder cachexia anorexia syn- drome.

But how, and where in the brain, do cannabinoids work to stimulate food intake? In this issue, Koch et al. 2 (page 45) report that, can be recreated in the real world. This will undoubtedly be difficult. It might also be possible to do this for other nanomaterials, but whether the simulated mechanism of nanodurotaxis will work for materials other than graphene is unknown. Nevertheless, the effort is certainly warranted, because strategic patterning of substrates might enable more- complicated trajectories to be realized, opening up new opportunities in nanoscale science and technology. Barnard is in the Virtual Nanoscience Laboratory, Commonwealth Scientific and Industrial Research Organisation, Parkville, Victoria 3052, Australia.

E-mail: amanda.barnard@csiro.au 1. Chang, I, Zhang, H., Guo, Z., Guo, X. Lett 114, 015504 (2015). Dundas, D., McEniry, E.

& Todorov, T. Nature Nanotechnol. 4, 99-102 (2009).

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& Stocker, R. 9, 494-498 (2013). When given in doses meant to simulate the effects of marijuana, cannabinoids surprisingly activate a subset of pro-opiomelanocortin (POMC) neurons, a cell group in the brains hypothalamus that has a central role in inhibit- ing hunger.

Previous work 3 has shown that ablation of POMC neurons, mutations in the gene encod- ing the POMC protein, and mutations in the melanocortin 4 receptor (MC4R) in down- stream cellular targets of POMC neurons, all cause severe overeating (hyperphagia) and obesity. Conversely, experimental stimulation of the POMC cell group produces a slow-onset inhibition of food intake 4,5. Cannabinoids bind to receptors dubbed CB^s (for cannabinoid A cellular basis for the munchies How does marijuana cause the irresistible hunger pangs known as the munchies? Paradoxically, the answer seems to involve an unusual mode of activation of a brain circuit best known for suppressing appetite. See Article p.45 38 NATURE VOL 519 5 MARCH 2015 © 2015 Macmillan Publishers Limited. All rights reserved RESEARCH NEWS & VIEWS Figure 1 1 Cannabinoid regulation of feeding circuits, a, The conventional view of appetite circuits in the brains hypothalamus involves Agouti-related protein (AgRP) neurons, which stimulate feeding, and pro-opiomelanocortin (POMC) neurons, which inhibit it.

Both groups affect downstream neurons expressing melanocortin 4 receptors (MC4Rs). 2 propose an alternative mechanism, in which cannabinoids stimulate food intake by causing a subset of POMC neurons to specifically activate (3-endorphin-releasing boutons (release sites, not shown), which target downstream neurons expressing p-opioid receptors, b, The authors suggest that, by activating cannabinoid receptor 1 (CB^) at two sites, cannabinoids increase feeding behaviour. At one site, they could inhibit release of the neurotransmitter GABA from AgRP neurons onto POMC neurons, thereby enhancing the latter neurons’ excitability. At the other site, CB^ activation in mitochondria could increase respiration, production of reactive oxygen species (ROS) and expression of mitochondrial uncoupling protein 2 (UCP2), which then acts as a switch to cause (3-endorphin release selectively onto downstream neurons. Receptor 1), and Koch and colleagues observe that, in mice, these receptors are found on nerve terminals that make synaptic connec- tions not only to POMC neurons, but also on organelles called mitochondria, in POMC neurons themselves.

This binding stimulates the specific release of an orexigenic (appetite- stimulating) neuropeptide called (3 -endorphin from the neurons, while somehow avoiding release of a-melanocyte-stimulating hormone (a-MSH), an appetite-suppressing peptide found in these same neurons (Fig. That cannabinoids can act at several brain regions to stimulate food intake is well estab- lished 6-8. So the striking lesson here is not so much the orexigenic effect of cannabi- noids through yet another of the many brain circuits involved in feeding behaviour.

It is rather that cannabinoids can subvert an appetite-inhibitory (anorexic) circuit to become orexigenic, which indicates that the POMC circuit may be even more complex than previously thought. Another challeng- ing concept arising from the present work is that, during the acute orexigenic response, cannabinoids stimulate these neurons par- tially through intracellular CEhRs, rather than through the more usually observed actions of cannabinoids at nerve terminals to regulate the release of substances such as the inhibitory neurotransmitter GABA. It is noteworthy that, at a neuroanatomical level, the POMC circuit is quite complex, with POMC neurons belonging to the arcuate cluster of cells sending axonal projec- tions to more than 100 brain regions. To add further complexity, a subset of these neurons responds to the hormone insulin; a different subset is affected by the hormone leptin 9, and roughly half of the cells may undergo inhibi- tory autoregulation by expressing the receptor MC3R (ref. Moreover, almost all POMC neurons produce not only (3-endorphin but also a-MSH. These neurons may therefore be differentially secreting neuropeptides and neurotransmit- ters to either suppress or stimulate appetite. Parenthetically, administration of analogues of y-MSH, another peptide released by POMC neurons, also has orexigenic effects 11, sug- gesting that (3 -endorphin may not be the only product of POMC neurons that can stimulate food intake.

Thus, the emerging picture of the arcuate POMC system is that of a circuit that can sense a wide array of signals and can then produce highly discriminatory responses through a differentiated set of circuits and molecular signalling mechanisms. What is remarkable about Koch and col- leagues’ findings is that cannabinoids seem to stimulate (3-endorphin release selectively from POMC neurons.

Consistent with this, the authors demonstrate that some 34% of the synaptic boutons, or release sites, on POMC neurons selectively express either (3-endorphin or a-MSH. There is, however, a nagging question about the proposed role of (3-endorphin as the main mediator of the orexigenic actions of admini- stered cannabinoids in POMC neurons. A previous study 12 found that deletion of the por- tion of the POMC gene encoding (3-endorphin produces hyperphagia and obesity rather than leanness, as might be expected if the primary role of the natural peptide is orexigenic. This issue can be readily addressed by testing whether there is a decrease in the orexigenic response to cannabinoid administration in mice carrying mutations in (3 -endorphin, or perhaps in mice lacking the p-opioid recep- tor, the target of (3 -endorphin in downstream neurons. The present data certainly make a clear case for the striking ability of cannabinoids to stimulate a small subset of arcuate POMC neurons and subsequently to increase food intake.

Nonetheless, the precise mechanisms of CB X R- induced activation of POMC neurons and selective (3-endorphin release remain to be fully elucidated. The authors propose two potential routes by which CBJt activation could boost POMC- neuron activity to increase feeding behaviour (Fig. First, low doses of CB: R stimulators could increase firing in a subset of POMC neurons, most likely by reducing the release of incoming GABA signals that would other- wise dampen the neurons’ activity 13. Thus, these stimulators could modify the balance of excitation and inhibition in this neuronal sub- set. However, a previous study demonstrated 14 that CB^ expression on neurons secreting the excitatory signal glutamate, rather than GABA, is required for the hyperphagic response to cannabinoids. Furthermore, increases in the firing rate of POMC neurons as a class reduces food intake 4, and thus cannot explain the hyperphagic effects of cannabinoids. So, the possibility of an alternative mechanism to cannabinoid- induced synaptic activation of a specific subset of POMC neurons requires further investigation.

Suggest that activation of mitochondrial CB X R represents just such an alternative. CB X R activation has been shown to block respiration in mitochondria by inhibit- ing the cAMP-PKA signalling pathway 15.

The authors now extend these findings to show that low levels of CB: R activation in fact increase mitochondrial respiration in POMC neurons as well as in neurons of the brain’s hippocam- pus. They propose a signalling pathway involv- ing CB^-induced increases in mitochondrial respiration, contact between mitochondria and another cellular organelle called the endoplas- mic reticulum, generation of reactive oxygen 5 MARCH 2015 VOL 519 NATURE 39 © 2015 Macmillan Publishers Limited. All rights reserved RESEARCH NEWS & VIEWS species and subsequent increased expression of mitochondrial uncoupling protein 2 (UCP2) — a regulator of both mitochondrial respiration in the hypothalamus and feeding (Fig. They show that UCP2 is essential for cannabinoid effects on mitochondrial respira- tion, (3 -endorphin release in the hypothalamus and feeding responses.

More definitive support for this provocative proposed mechanism could be provided by demonstrating that cell-impermeable inhibitors of CE^R do not block feeding induced by CB: R activators. Still unknown are the relative dominance of various CE^R sites in the central nervous system in the orexigenic action of administered cannabinoids, and the relative importance of cell-surface and mitochondrial CEhRs. Regardless of this, Koch et al. Provide another striking example of the complexity of the POMC circuits, and a new cellular mechanism by which cannabinoids stimulate feeding behaviour. ■ Sachin Patel and Roger D. Cone are at the Vanderbilt University Medical Center, Department of Molecular Physiology and Biophysics, Nashville, Tennessee, USA.

E-mail: roger.cone@vanderbilt.edu 1. United Nations Office on Drugs and Crime. World Drug Report 2014 ( UN, 2014).

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This article was published online on 18 February 2015. MOLECULAR BIOLOGY Signals across domains of life Signal sequences on messenger RNA that initiate protein synthesis are not thought to be interchangeable between life’s domains. The finding that a signal from an arthropod virus can function in bacteria questions this idea. See Letter p.110 ERIC JAN A ll domains of life, from prokaryotes (archaea and bacteria) to eukaryotes (organisms that include plants, animals and fungi) use the ribosome appara- tus to synthesize proteins by translat- ing genetic code carried by messenger RNAs. Although the general steps of protein synthesis are evolutionarily conserved, the way in which ribo- somes are recruited to an mRNA mol- ecule differs depending on the specific phylogenetic domain 1. In this issue, Colussi et al.

2 (page 110) reveal the surprising finding that a eukaryotic ribosome-recruiting signal is func- tional in prokaryotic bacteria, thereby challenging the prevailing dogma that prokaryotic and eukaryotic ribosome recruitment are mutually exclusive. In prokaryotes, ribosomes are generally recruited by a specific signal on the mRNA called the ribo- some-binding site (RBS, also called the Shine-Dalgarno sequence). The RBS positions the ribosome over the AUG start codon, a sequence that ini- tiates protein synthesis 1. By contrast, eukaryotic mRNAs do not contain an RBS, but instead contain covalent modifications — the 5' cap at the 5' end, and a poly (A) tail at the 3' end — that promote the recruitment of ribosomes and protect the mRNA from degradation.

Eukaryotes also use at least 12 protein initia- tion factors (compared to three in prokaryotes) that help to recruit the small subunit of the b Reposition ribosome to the 5' cap and facilitate scanning of the mRNA by the ribosome to find the AUG codon. Some eukaryotic viral RNAs contain alternative signals called internal ribosome entry sites 3 (IRESs) to recruit the ribosome. When host-protein synthesis is inactivated during virus infection, an IRES can bypass normal signals, such as the 5' cap and some initiation factors, to enlist the ribo- some for viral protein synthesis.

The sim- plest known IRES lies within regions found between the genes of dicistroviruses — a family of RNA viruses that infect arthropods 4. Dicistrovirus IRESs are about 200 nucleotides long and fold into a unique RNA structure. What makes them so remarkable is their abil- ity to bind directly to the ribosome without the need for any initiation factors and to initiate protein synthesis at a non-standard start codon 5 (not AUG). Structural 6 and biochemical studies 7 have shown that part of the IRES structure binds to the conserved core of the ribo- some by mimicking a transfer RNA, which normally delivers an amino acid to the growing protein chain. The dicistrovirus IRES has therefore evolved to mimic a component of the normal translational machinery, per- mitting the viral RNA to hijack the ribosome.

Colussi and colleagues tested whether the dicistrovirus IRES can function in bacteria. To do this, they constructed mRNA that encodes reporter proteins — in this case, luminescent proteins. They found that inclusion of the IRES into the mRNA promotes expression of the reporter proteins in the bacterium Escheri- chia coli. Impressively, the research- ers generated a comprehensive set of mutations within the IRES to work out how it functions in bacteria. They observed that some mutations that disrupt the IRES RNA structure Figure 1 1 Internal ribosome entry sites trigger protein synthesis in bacteria. Structures called internal ribosome entry sites (IRESs) in RNA viruses such as the dicistrovirus promote protein synthesis in eukaryotes (organisms including plants, animals and fungi).

Colussi et al. 2 report the surprising finding that the dicistrovirus IRES can initiate protein synthesis in the bacterium Escherichia coli (a prokaryote), a, The authors constructed a messenger RNA that incorporates the IRES and introduced this to E. Coli cells, where the IRES recruits the bacterial ribosome (the protein-synthesizing apparatus) to the mRNA. B, They propose that the ribosome then repositions itself to a ribosome-binding site (RBS) and an AUG start codon (an RNA sequence that initiates translation), c, Another hypothesis is that, after recruitment of the first ribosome, a second ribosome binds to the RBS and AUG codon. 40 NATURE VOL 519 5 MARCH 2015 © 2015 Macmillan Publishers Limited. All rights reserved RESEARCH NEWS & VIEWS reduced expression of the reporter proteins, demonstrating that the integrity of this struc- ture is crucial for function. To gain further insight into how IRESs that evolved to hijack ribosomes in eukaryotes can work in prokaryotic bacteria, Colussi et al.

Used X-ray crystallography to acquire a high- resolution image of the dicistrovirus IRES bound to the bacterial ribosome. Remarkably, the IRES binds to the ribosomal core, which is present across all domains of life, thus explain- ing how it can interact with both eukaryotic and bacterial ribosomes. The authors also show that an IRES structure from an unrelated virus — classical swine fever virus — does not support reporter-protein expression in bac- teria, indicating that only the dicistrovirus IRES enables ribosome recruitment in E. But that is not the whole story. The investigators found that maximal reporter expression in bacteria depends not only on the IRES, but also on an RBS hidden in the reporter-system sequence and on an AUG start codon of the reporter mRNA.

Moreover, their mutational analysis indicated that protein synthesis does not start at the IRES, but at the AUG codon. Colussi and co-workers therefore propose that, after being recruited to the IRES, the bacterial ribosome moves downstream to interact with the RBS and to start protein synthesis at the AUG codon (Fig. Alterna- tively, another ribosome might be recruited to the RBS and initiate protein synthesis, a model that needs to be examined further.

It therefore seems that the authors reporter system uses a hybrid of eukaryotic and prokary- otic signals to promote protein synthesis in bacteria. In prokaryotic translation, RNA structures are dynamic, and some can control protein expression by either burying the RBS within their structure or altering conformation to expose the RBS for ribosome recruitment 8. Although leaderless RNAs — which are trans- lated in the absence of the signals that usually support ribosome binding and translation effi- ciency — can also function across domains 9, Colussi et al. Have shown for the first time that a bona fide signal in an RNA structure promotes protein synthesis in two domains of life. This exciting study raises new questions. If the bacterial ribosome repositions itself from the IRES to the RBS, as the authors suggest, then how does it do so? Is the movement akin to ribosomal scanning of mRNAs in eukary- otes?

And does the IRES function in bacteria without initiation factors, as it does in eukary- otic cells? Colussi and colleagues report that the dicistrovirus IRES binds to bacterial ribosomes slightly differently and more tran- siently than it does to eukaryotic ribosomes. Importantly, the IRES interacts with eukary- otic ribosomal protein rpS25, which is not present in bacterial ribosomes 10. Further studies are needed to address how the IRES manipulates bacterial ribosomes. Although the IRES functions in bacteria, does this phenomenon have a physiological role, and do other bacterial RNA structures function similarly? Another question is whether the IRES could work in archaea, or interact with the prokaryotic-like ribosome of mitochondria (specialized organelles that act as cellular powerhouses). And could the IRES be a remnant of a molecular fossil of the ancient £ RNA world’ that is widely presumed to have preceded the evolution of DNA and proteins?

Finally, this study opens up the pos- sibility that other RNA structures function as signals across domains, and that eukaryotes and bacteria have more in common than was previously thought. ■ Eric Jan is in the Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada. MATERIALS SCIENCE MATHIAS ULBRICHT S ynthetic membranes, filters and micro - valves have been developed for applica- tions such as mass separation, analytics and medical therapies. But there is great inter- est in making these engineered systems smarter’, by enabling biomimetic, tunable and gated selective permeation through a barrier. On page 70 of this issue, Hou et al. 1 report the proof of principle for such a gating mecha- nism, using pores that respond to pressure by reversibly switching between a liquid-filled closed’ state and an open’ state in which the liquid wets the pores’ surface. Many sophisticated and efficient barrier sys- tems are found in nature that define, organize and protect cells, tissue and organisms.

The most intriguing feature of such membranes is their ability to allow the highly selective move- ment of molecules or particles, or of bulk fluids (gases or liquids), through the barrier. Biologi- cal membranes are also dynamic: their perme- ability can respond to signals, enabling gating mechanisms, and they can have non -fouling or self-cleaning properties. Some of these sys- tems have liquid-filled pores, and range from subnanometre-sized water-selective channels to micrometre- scale pores in lungs. The opening of liquid-filled pores at specific e-mail: ej@mail.ubc.ca 1. & McCarthy, J.

68, 991-1003 (2011). Nature 519, 1 10-1 13 (2015). 15, 1593-1612(2001). 55, 129-150(2010).

E., Pestover, C. V., Hellen, C. Cell 102,511-520 (2000). Fernandez, I. C., Murshudov, G., Scheres, S. & Ramakrishnan, V.

Cell 157, 823-831 (2014). Pfingsten, J. S., Costantino, D. Science 314, 1450-1454 (2006). Cold Spring Hard. 4, 003566 (2012). Moll, I., Grill, S., Gualerzi, C.

43, 239-246 (2002). Nishiyama, I, Yamamoto, H., Uchiumi, T. & Nakashima, N. Nucleic Acids Res. 35, 1514-1521 (2007). This article was published online on 4 February 2015. Gas pressures has long been used as a way of characterizing synthetic membranes, such as polymeric sterile filters that have typical bar- rier pore diameters of 0.5-0.

1 micrometres; the pressure at which gas bubbles start to evolve from such membranes is related to the diam- eter of the largest pores or defects 2. If the gas- liquid system in these tests is replaced by two immiscible liquids, smaller pores (down to a few nanometres) can also be analysed using pressures that will not mechanically damage the mem- brane, because the interfacial tension between two liquids is smaller than that between a gas and a liquid 3. However, the pore-filling liquid is usually expelled during these tests, leaving the pore open for unrestricted fluid flow. By contrast, Hou and colleagues’ pore gating system (see Fig. Lb of the paper 1 ) retains the pore-filling liquid, and is used in barriers that have pore sizes larger than 0.1 pm. The authors find that the pore -filling liquid must have a high affinity for the membrane poly- mer and be immiscible with the second liquid.

Gating mechanism under pressure Liquid -filled pores in membranes have been designed to reversibly open and close, allowing only particular fluids through at given pressures. This enables tunable and gated separations of mixtures of immiscible fluids. See Letter p.70 The reversibility and antifouling properties make these dynamic systems superior to conventional solidfilter materials. 5 MARCH 2015 VOL 519 NATURE 41 © 2015 Macmillan Publishers Limited.

All rights reserved RESEARCH NEWS & VIEWS reduced expression of the reporter proteins, demonstrating that the integrity of this struc- ture is crucial for function. To gain further insight into how IRESs that evolved to hijack ribosomes in eukaryotes can work in prokaryotic bacteria, Colussi et al.

Used X-ray crystallography to acquire a high- resolution image of the dicistrovirus IRES bound to the bacterial ribosome. Remarkably, the IRES binds to the ribosomal core, which is present across all domains of life, thus explain- ing how it can interact with both eukaryotic and bacterial ribosomes. The authors also show that an IRES structure from an unrelated virus — classical swine fever virus — does not support reporter-protein expression in bac- teria, indicating that only the dicistrovirus IRES enables ribosome recruitment in E. But that is not the whole story. The investigators found that maximal reporter expression in bacteria depends not only on the IRES, but also on an RBS hidden in the reporter-system sequence and on an AUG start codon of the reporter mRNA. Moreover, their mutational analysis indicated that protein synthesis does not start at the IRES, but at the AUG codon.

Colussi and co-workers therefore propose that, after being recruited to the IRES, the bacterial ribosome moves downstream to interact with the RBS and to start protein synthesis at the AUG codon (Fig. Alterna- tively, another ribosome might be recruited to the RBS and initiate protein synthesis, a model that needs to be examined further. It therefore seems that the authors reporter system uses a hybrid of eukaryotic and prokary- otic signals to promote protein synthesis in bacteria. In prokaryotic translation, RNA structures are dynamic, and some can control protein expression by either burying the RBS within their structure or altering conformation to expose the RBS for ribosome recruitment 8.

Although leaderless RNAs — which are trans- lated in the absence of the signals that usually support ribosome binding and translation effi- ciency — can also function across domains 9, Colussi et al. Have shown for the first time that a bona fide signal in an RNA structure promotes protein synthesis in two domains of life. This exciting study raises new questions.

If the bacterial ribosome repositions itself from the IRES to the RBS, as the authors suggest, then how does it do so? Is the movement akin to ribosomal scanning of mRNAs in eukary- otes? And does the IRES function in bacteria without initiation factors, as it does in eukary- otic cells?

Colussi and colleagues report that the dicistrovirus IRES binds to bacterial ribosomes slightly differently and more tran- siently than it does to eukaryotic ribosomes. Importantly, the IRES interacts with eukary- otic ribosomal protein rpS25, which is not present in bacterial ribosomes 10. Further studies are needed to address how the IRES manipulates bacterial ribosomes.

Although the IRES functions in bacteria, does this phenomenon have a physiological role, and do other bacterial RNA structures function similarly? Another question is whether the IRES could work in archaea, or interact with the prokaryotic-like ribosome of mitochondria (specialized organelles that act as cellular powerhouses). And could the IRES be a remnant of a molecular fossil of the ancient £ RNA world’ that is widely presumed to have preceded the evolution of DNA and proteins?

Finally, this study opens up the pos- sibility that other RNA structures function as signals across domains, and that eukaryotes and bacteria have more in common than was previously thought. ■ Eric Jan is in the Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada. MATERIALS SCIENCE MATHIAS ULBRICHT S ynthetic membranes, filters and micro - valves have been developed for applica- tions such as mass separation, analytics and medical therapies. But there is great inter- est in making these engineered systems smarter’, by enabling biomimetic, tunable and gated selective permeation through a barrier. On page 70 of this issue, Hou et al.

1 report the proof of principle for such a gating mecha- nism, using pores that respond to pressure by reversibly switching between a liquid-filled closed’ state and an open’ state in which the liquid wets the pores’ surface. Many sophisticated and efficient barrier sys- tems are found in nature that define, organize and protect cells, tissue and organisms. The most intriguing feature of such membranes is their ability to allow the highly selective move- ment of molecules or particles, or of bulk fluids (gases or liquids), through the barrier.

Biologi- cal membranes are also dynamic: their perme- ability can respond to signals, enabling gating mechanisms, and they can have non -fouling or self-cleaning properties. Some of these sys- tems have liquid-filled pores, and range from subnanometre-sized water-selective channels to micrometre- scale pores in lungs. The opening of liquid-filled pores at specific e-mail: ej@mail.ubc.ca 1. & McCarthy, J. 68, 991-1003 (2011). Nature 519, 1 10-1 13 (2015).

15, 1593-1612(2001). 55, 129-150(2010).

E., Pestover, C. V., Hellen, C. Cell 102,511-520 (2000). Fernandez, I. C., Murshudov, G., Scheres, S.

& Ramakrishnan, V. Cell 157, 823-831 (2014). Pfingsten, J. S., Costantino, D. Science 314, 1450-1454 (2006). Cold Spring Hard. 4, 003566 (2012).

Moll, I., Grill, S., Gualerzi, C. 43, 239-246 (2002). Nishiyama, I, Yamamoto, H., Uchiumi, T. & Nakashima, N. Nucleic Acids Res.

35, 1514-1521 (2007). This article was published online on 4 February 2015. Gas pressures has long been used as a way of characterizing synthetic membranes, such as polymeric sterile filters that have typical bar- rier pore diameters of 0.5-0. 1 micrometres; the pressure at which gas bubbles start to evolve from such membranes is related to the diam- eter of the largest pores or defects 2. If the gas- liquid system in these tests is replaced by two immiscible liquids, smaller pores (down to a few nanometres) can also be analysed using pressures that will not mechanically damage the mem- brane, because the interfacial tension between two liquids is smaller than that between a gas and a liquid 3. However, the pore-filling liquid is usually expelled during these tests, leaving the pore open for unrestricted fluid flow.

By contrast, Hou and colleagues’ pore gating system (see Fig. Lb of the paper 1 ) retains the pore-filling liquid, and is used in barriers that have pore sizes larger than 0.1 pm. The authors find that the pore -filling liquid must have a high affinity for the membrane poly- mer and be immiscible with the second liquid. Gating mechanism under pressure Liquid -filled pores in membranes have been designed to reversibly open and close, allowing only particular fluids through at given pressures. This enables tunable and gated separations of mixtures of immiscible fluids. See Letter p.70 The reversibility and antifouling properties make these dynamic systems superior to conventional solidfilter materials.

5 MARCH 2015 VOL 519 NATURE 41 © 2015 Macmillan Publishers Limited. All rights reserved RESEARCH NEWS & VIEWS The gating mechanism is based on established physical principles, and depends largely on the interfacial tensions between the pore surface, the pore-filling liquid and the fluid passing through the membrane. The pressure needed to open the pores (the gating threshold) to allow different bulk fluids to pass through can be adjusted by changing the polymeric membrane material, the pore size and the pore-filling liquid. Hou and colleagues observed that the gating threshold can be varied over a wide range. Impressively, they show that systems can be set up so that air dispersed in water preferentially passes through the barrier under tunable conditions: at low pressure, the membrane is closed; beyond the critical pres- sure of air, all bubbles are removed from an air- water stream; and only beyond the second critical pressure does water also flow through the membrane. The reverse selectivity for such phase sorting was also demonstrated, in which a gate opens at a lower pressure for a liquid than for a gas. The authors report that three -component gas-liquid-liquid mixtures can also be sepa- rated by successively increasing the pressure across the membrane (see Fig.

3 of the paper 1 ), and that the gating system has robust reversi- bility. Furthermore, they demonstrate that little fouling of the liquid-lined pore surface occurs when various particle-loaded liquids, includ- ing blood, are passed through the system. The reversibility and antifouling properties derive from the use of a liquid in the selective barrier, and make these dynamic systems superior to conventional solid filter materials. The data suggest a range of applications for the authors gating system, but there are poten- tial challenges ahead. For example, long-term gating stability will be guaranteed only if the two liquids are completely immiscible. And the more complex the composition of the feed, the higher the risk that the pore-filling liquid will be extracted or polluted, which would change the interfacial tension. More- over, achieving completely reversible reconfig- uration of the pore-filling liquid will become more complicated as the aspect ratio (the ratio of length to width) of a pore increases, because some of the liquid is likely to be expelled.

Designing a reservoir for temporarily expelled liquid could be a straightforward solution to this problem, however. There are upper and lower limits to the pore sizes that can be used for phase sorting. For pores larger than a few tens of micrometres, the gating thresholds will be too low and close together to use for phase sorting.

Lower limits in the submicrometre range are set by the membranes stability to high gating thresh- olds, although this problem might be solved by using ceramic membranes instead of poly- meric ones. Furthermore, when the thick- ness of the pore-lining liquid film is close to the pore radius, irregularities in pore size or shape will prevent defined gating. Membranes with well-controlled pore morphology might be needed. Separations of homogeneous fluid mixtures are not possible using the new gating system, but stimulus-responsive membranes for ultra- filtration (which requires pore sizes between 50 nm and 2 nm) can be realized in a conceptu- ally analogous way.

For example, membranes have been reported 4 in which pore-filling gels reversibly switch between a closed ultrafilter- ing and an open macrofiltering state. Mem- branes formed from self- assembled polymers have also been made in which the nanoscale pore size can be tuned by applying a pre- selected transmembrane pressure 5. So how might Hou and colleagues’ system be used?

Previous work 6 from the same research group described the preparation of slippery surface-immobilized liquid films that have good antifouling properties. If such films were used on the surface of pores or micro- fluidic channels, then it might be possible to make highly robust gating systems that have exceptionally good non-fouling properties. CATALYSIS JAMES J. DEVERY III & COREY R.

STEPHENSON D ifficulties can arise when developing reactions for the production of phar- maceuticals, industrial chemicals and materials if the chemical properties of the reac- tion components enable undesired products to form. Suppression of side reactions can therefore be just as important a consideration as how to obtain the synthetic target. Catalysis allows chemists to circumvent side products by inducing otherwise unreactive compounds to become selectively reactive.

Even more con- trol over reaction outcomes can be gained if reactivity can be induced by the flick of a light switch. On page 74 of this issue, Cuthbertson and MacMillan 1 report their use of visible- light-mediated catalysis to induce atypical activity of reaction substrates, initiating a com- plex transformation of otherwise unreactive components.

Photosynthesis is the archetypal example of how light can facilitate chemical reactions. During the day, plants absorb visible light and The integration of smart, liquid-filled porous valves in microfluidic systems could also enable the delivery of two -phase liquid mix- tures at compositions and droplet sizes far from thermodynamic equilibria.

This would be attractive for several applications, such as the in situ formulation of inks in advanced printing technologies. ■ Mathias Ulbricht is at the Lehrstuhlfur Technische Chemie II, Department of Chemistry, and the Center for Nanointegration Duisburg-Essen (CENIDE), Universitat Duisburg-Essen, 45117 Essen, Germany, e-mail: mathias.ulbricht@uni-due.de 1. Hou, X., Hu, Y., Grinthal, A., Khan, M. & Aizenberg, J. Nature 519, 70-73 (2015). Basic Principles of Membrane Technology 2nd edn (Kluwer, 1996). 132, 131-145 (1997).

& Ulbricht, M. 22, 3088-3098 (2012). Edn 51, 7166-7170 ( 2012 ). Direct its energy to generate the molecules that fuel their lives, through chemistry that involves the transfer of single electrons.

This intricate process uses light-activated catalysts to induce the desired electron transfer. Water acts as the source of electrons that allows photosynthetic complexes to complete their catalytic cycle 2. This light-promoted system enables reactiv- ity that chemists have striven to replicate for decades 3.

A form of light- activated catalysis called photoredox catalysis has become established as a powerful tool for initiating organic trans- formations mediated by free radicals 4. Typical photoredox catalysts are transition-metal com- plexes or organic dyes that facilitate reactions in the presence of visible light. Methods using these compounds are at the forefront of single- electron transfer (SET) in organic synthesis because they are high-yielding, can be per- formed at room temperature and require fewer toxic reagents than other techniques. The fact that such mild’ conditions can be used means that photoredox reactions are compatible with a wide variety of compounds. Nature 477, 443-447 (2011).

Dual catalysis at the flick of a switch A combination of two catalysts — one of which is light -activated — has been used to promote new chemical reactivity, opening up fresh opportunities for the synthesis of structurally complex organic molecules. See Letter p.74 42 NATURE VOL 519 5 MARCH 2015 © 2015 Macmillan Publishers Limited.