News this Week

Science  08 Nov 2013:
Vol. 342, Issue 6159, pp. 676
1. Around the World

1 - Rotterdam, the Netherlands
Virologist Appeals Decision on H5N1 Export Rules
2 - Amman
Banana Disease Reaches Jordan
3 - Washington, D.C.
Report Finds Research Gaps on Youth Concussion in Sports
4 - London
Personal Genome Projects Spread to Europe
5 - Brussels
E.U. Parliament Approves Some Deep-Sea Fisheries Restrictions
6 - New Delhi
India Launches Mars Orbiter

Rotterdam, the Netherlands

Virologist Appeals Decision on H5N1 Export Rules

The legal battle continues between virologist Ron Fouchier and the Dutch government over the publication of research on the H5N1 avian influenza virus. On 1 November, Fouchier's employer, Erasmus MC in Rotterdam, formally appealed a ruling by a Dutch court that the government could limit Fouchier's freedom to publish his work with the virus. The issue will now come before Amsterdam's Court of Appeal.

Erasmus MC had sued over the government's demand that Fouchier apply for an export license before submitting a paper to Science, published in 2012, that described how a few mutations can make H5N1 transmissible between ferrets. On 20 September, the district court in Haarlem ruled that the government had correctly interpreted an E.U. regulation seeking to slow the proliferation of weapons of mass destruction.

The European Society for Virology (ESV) has sided with Fouchier. In a letter to European Commission President José Manuel Barroso, ESV President Giorgio Palù warns that "this Dutch ruling may have far-stretching implications for research and public and animal health within all EU Member States" and urges a debate on the issue at the European level. http://scim.ag/Fouchfight

Amman

Banana Disease Reaches Jordan

One of the most damaging diseases of banana plants has spread beyond Southeast Asia. Fusarium wilt, or "Panama disease," is caused by a soil fungus that wiped out banana plantations by the mid-20th century, until they were replanted with a resistant crop. But 20 years ago, a devastating new variant of the fungus, tropical race 4 (TR4), emerged in Taiwan. It has spread to several countries including China, the Philippines, and Australia.

Now, scientists have confirmed that TR4 is in Jordan. Although only 1500 hectares there are planted with bananas, 80% of the area is infected, underscoring concerns about how easily the pathogen can spread. Researchers from Wageningen University in the Netherlands and other institutions analyzed DNA from fungus samples collected by the Jordanian Ministry of Agriculture and confirmed that they were TR4, the scientists reported online in Plant Disease. The researchers called the jump from Asia a "dangerous expansion" of the range and fear that the disease will reach Africa and Latin America, which not only export many bananas but also rely on them for food security.

Washington, D.C.

Report Finds Research Gaps on Youth Concussion in Sports

A report released last week by the Institute of Medicine highlights large gaps in knowledge about sports-related concussions in youth. Most published research on these concussions has been conducted in adults, but it's dangerous to assume those findings can be mapped onto children, because of changes that occur during brain development.

There's not yet enough scientific data to guide safety programs such as the Hit Count Initiative launched last year by the Sports Legacy Institute, which aims to set a threshold for a "safe" number of hits to the head, the report finds. Also unclear is the benefit of preventative measures such as wearing helmets—although they can prevent skull fractures, no available evidence suggests that they prevent concussion. Large, controlled, randomized studies will be needed to answer questions such as whether concussions sustained in childhood can result in long-term problems.

The panel recommends that the Centers for Disease Control and Prevention set up a national surveillance system to monitor the incidence of sports-related concussions, and it recommends that the National Institutes of Health, the Department of Defense, and organizations such as the National Collegiate Athletic Association support research to develop better age-specific recommendations and rules. http://scim.ag/youthconcussion

London

Personal Genome Projects Spread to Europe

The move to make individual genome sequences—and accompanying personal health information—freely accessible online just got a boost in the United Kingdom. This week, Stephan Beck from University College London and his colleagues announced the establishment of a British Personal Genome Project (PGP), which will recruit volunteers to provide DNA and health data with no restrictions on their use. This PGP is an outgrowth of a project begun in 2005 by Harvard University's George Church. Often, genome data are freely available, but health information is not because of privacy concerns, making it difficult for researchers to link gene variants to specific conditions. As the PGP coffers grow, researchers will be able to use these data however they need to to inform their disease-gene links studies, Church says. PGP-UK (personal genomes. org.uk) has funding through the first year to sequence 50 British residents, age 18 or older, and ultimately hopes to enroll 100,000. Already, about 450 have expressed interest, Beck says. All participants have to read and pass a test about a 24-page consent form detailing risks. http://scim.ag/persgens

Brussels

E.U. Parliament Approves Some Deep-Sea Fisheries Restrictions

After months of delays, the European Parliament's Fisheries Committee approved a report on 4 November to restrict fishing practices deemed destructive for deep-sea ecosystems. But the committee did not back the European Commission's proposal to ban bottom trawling and gillnetting altogether.

Deep-sea trawling fisheries catch 20% to 40% of unwanted fish. About 300 marine scientists signed a petition in favor of the ban, released in June by a French marine conservation nongovernmental organization.

The Fisheries Committee agreed to close off areas harboring vulnerable marine ecosystems to bottom trawling. It also left the door ajar for a general phaseout based on an assessment of the impact of deep-sea fishing gear after 4 years.

The draft legislation will need to be approved by the whole Parliament plenary, possibly in December or January, before negotiations with member states begin. Fisheries ministers will also need to sign off on the plan. http://scim.ag/deepseatrawl

India this week sent an orbiter on a journey to Mars. The successful launch of Mangalyaan—meaning "Mars craft" in Hindi—is the culmination of a $72 million effort by the Indian Space Research Organisation (ISRO). "Capturing and igniting the young minds of India and across the globe will be the major return from this mission," mission director P. Kunhikrishnan told reporters on 5 November. Although aimed primarily at show casing the country's technological prowess, the mission is also supposed to deliver science. The orbiter has six instruments on board that will image the martian surface, sniff the upper atmosphere for traces of methane, and measure the ratio of atmospheric deuterium to hydrogen to understand how the martian atmosphere thinned out over time. But first the spacecraft must travel more than half a million kilometers over 300 days to get into martian orbit. "The biggest challenge will be precisely navigating the spacecraft to Mars," K. Radhakrishnan, ISRO's chairman, told reporters. "We will know if we pass our examination on 24 September 2014." 2. Random Sample Elephants Haunted by Mass Killings African elephants that have lived through a selective killing, or cull, remain psychologically damaged by the experience for decades, finds a study in the current issue of Frontiers in Zoology. Wildlife officials in South Africa culled elephant populations in the 1960s to the 1990s out of fear that they would otherwise destroy the habitat. The officials would save the young elephants 4 to 10 years old from a family and ship them to other parks. In the new study, researchers compared the reactions of 14 elephant families in Pilanesberg National Park in South Africa (a relocation site) and 39 elephant families in Kenya's Amboseli National Park (a relatively undisturbed population) to social threats. The team would broadcast a call from an unfamiliar older female elephant (possibly another family's matriarch). The Amboseli elephants responded appropriately, with coordinated defensive behaviors, but the Pilanesberg elephants were at a loss, the researchers said—because they never learned the proper behaviors from their own matriarchs. That poor decision-making could be passed down to future generations, affecting reproductive success. http://scim.ag/elephanthaunt Whose Brain Is It Anyway? Many scientists have tried to find out where, in the winding topography of the human brain, genius resides. For instance, in the middle of the 19th century, German anatomist Rudolf Wagner collected the brains of numerous professors to study them in detail. The star of the cerebral collection, examined many times in the past 150 years: the brain of German genius and "Prince of Mathematics" Carl Friedrich Gauss. But when Renate Schweizer of the Max Planck Institute for Biophysical Chemistry in Göttingen, Germany, recently examined the brain in the University of Göttingen's collection labeled "C. F. Gauss," she noticed a rare anatomical feature in the left hemisphere: a bit of brain tissue bridging the central fissure between the frontal and parietal lobe. "My first thought was, 'Wow, Gauss had this rare feature,' " Schweizer says. Her second thought was: Wait, I've seen this exact central fissure before. Her conclusion, published last month in Brain: The brain labeled as Gauss's was that of a doctor, Conrad Heinrich Fuchs, whose brain Wagner had also examined. In fact, Wagner had used it to describe for the first time the very anatomical feature Schweizer had noticed. Exactly how and when the brains were mixed up is still unclear, but Schweizer says the culprit was probably Wagner's son Hermann, who compared the brains for his 1864 doctoral thesis—meaning that generations of scientists have examined Fuchs's brain instead of Gauss's. No textbooks will have to be rewritten, however. Anatomically, Gauss's brain is even less exceptional than its long-term substitute, Schweizer says. ScienceLIVE Join us on Thursday, 14 November, at 3 p.m. EST for a live chat on robotics and neuroprosthetics. http://scim.ag/science-live 3. Newsmakers Three Q's Last week, Texas Governor Rick Perry lifted a 10-month moratorium on new grants from the$3 billion Cancer Prevention and Research Institute of Texas (CPRIT). The freeze followed months of controversy over improperly reviewed grants that led the agency's chief scientific officer, Nobelist Alfred Gilman, to resign. Heading the overhauled CPRIT's new eight-member Scientific Review Council is Ludwig Institute, San Diego, California, branch cancer geneticist Richard Kolodner, the only council member who did not step down last year.

Q:Why did you agree to stay on with CPRIT?

R.K.:Because in this day of declining federal funding for cancer and biological sciences research coming on top of many years of slow degradation of individual NIH [National Institutes of Health] grant budgets, programs that provide significant funding are very important and need to be nurtured.

Q:Are you confident that last year's problems won't happen again?

R.K.:I think CPRIT has … reassessed its leadership and procedures, and is ready to move forward with its mission. … I have great confidence that [Chief Scientific Officer] Margaret Kripke will build on the tradition of excellence that Al Gilman and [former Scientific Review Council Chair] Phil Sharp established and help CPRIT succeed and continue to fund excellent cancer research.

Q:Will you be able attract the same caliber of reviewers?

R.K.:Virtually all of the previous reviewers I have contacted have expressed a strong interest in participating as reviewers again. Frankly I think it is attractive to review grants under circumstances where you know that most if not all of the worthy grants are likely to get funded.

4. The Forgotten Malaria

1. Gretchen Vogel

Long considered "benign," the malaria parasite Plasmodium vivax threatens billions while eluding control measures. Now, scientists are going on the offensive.

It has plagued english kings and as many as eight U.S. presidents—including George Washington and Abraham Lincoln—and may have helped kill Genghis Khan. It causes wracking fever and chills, headaches and muscle pain, and can lead to severe anemia. After you think you have beaten it, it can return again, months or even years later, starting the same cycle of misery. Roughly one-third of the world's population is thought to be at risk, mostly in Asia and Latin America. And almost no one has ever heard of it.

It is Plasmodium vivax, one of the five Plasmodium species that infect humans and cause malaria (see table, p. 685). For many years, vivax malaria was officially called "benign" malaria, in contrast to the "malignant" variety caused by its cousin Plasmodium falciparum. Falciparum malaria is undeniably deadly, killing more than 650,000 people each year—mostly children in sub-Saharan Africa—and accounting for more than 90% of global malaria deaths. Because it is so lethal, it has received most of the attention—and funding—in the global fight against the disease.

In contrast, vivax malaria has long been an afterthought in both public health plans and in research funding. But that is beginning to change, in part because the global campaign against malaria is starting to pay off. Since the wide-scale introduction of bed nets and new drugs, malaria rates have fallen dramatically across the globe. There is even talk about eventually eradicating the disease (Science, 7 December 2007, p. 1544). But vivax malaria can evade some of the standard malaria-fighting tools, so as overall rates of malaria fall in a region, the proportion of cases that are caused by P. vivax increases. And although vivax malaria kills fewer people, it is decidedly not benign. "The saying used to go: Vivax malaria doesn't kill you, but you feel like it will," says Robert Newman, director of the Global Malaria Programme at the World Health Organization (WHO) in Geneva, Switzerland.

Now, as public health leaders intensify their push to eliminate the disease from more and more regions, they are also starting to give P. vivax special attention. For the first time, Newman says, WHO is drawing up a specific plan to address vivax malaria as part of its updated global malaria-fighting strategy, due out in 2015. The plan is likely to include, for example, better diagnosis of parasite species in patients and updated treatment guidelines. "We have recognized the deficiencies of always making vivax an afterthought," he says. The fight against vivax may also benefit from a new drug to overcome the parasite's best defense: its ability to lie dormant in the human liver.

Richard Feachem, the director of the Global Health Group at the University of California, San Francisco, who has long warned about the threat of vivax malaria, argues that such strategies will be crucial to defeating malaria. "The final battle against malaria is a battle against vivax."

A formidable foe

In several ways, Plasmodium vivax is even more exquisitely adapted to its human host than P. falciparum is. Unlike P. falciparum, P. vivax can populate the bloodstream with sexual-stage parasites—the form picked up by mosquitoes on their way to the next victim—even before a patient shows symptoms. That means treating symptomatic patients promptly doesn't necessarily help stop an outbreak, as it does with falciparum malaria, in which fevers occur at the same time as sexual stages develop. When the debilitating symptoms do set in, they make the human host miserable but are usually not fatal—at least in the short term—which allows the parasite to continue multiplying. And when vivax hides out in the liver, it causes no symptoms and is undetectable in blood tests, only to reappear weeks or even many months later, once again tormenting the human host and ready, again, to infect new mosquitoes.

"Falciparum kills you quickly. Vivax kills you slowly," says malaria researcher Ric Price of the University of Oxford in the United Kingdom and the Menzies School of Health Research in Darwin, Australia. At first glance, clinical cases of both vivax and falciparum malaria look similar. Both cause the classic symptoms of alternating fever, chills, and sweats. Both kinds of malaria invade the blood. But whereas P. falciparum attacks red blood cells of all ages, P. vivax targets reticulocytes, immature red blood cells that are relatively rare, which can make vivax infections hard to diagnose. When P. falciparum invades red blood cells, it makes them rigid, which is thought to lead to blocked capillaries, a factor in the deadly cerebral malaria. Blood cells infected with P. vivax seem to remain pliable, which might explain why it isn't quite as lethal.

How and why P. vivax causes severe malaria is unclear, but recurrent episodes leave people chronically anemic—children are especially vulnerable, Price notes. A single infectious bite can trigger six or more relapses a year, as the dormant parasites in the liver activate and cause a new bout of disease. Fighting off those episodes can leave people more vulnerable to other diseases—and to poverty and malnutrition, because they can't work while ill. Other infectious diseases, including falciparum malaria, also exacerbate the disease because they seem to trigger relapses. "It's a cofactor in a lot of people's deaths," says Simon Hay, an epidemiologist at the University of Oxford.

As researchers delve into vivax malaria, it is becoming apparent just how little is known about the parasite. Much of the research on it was done more than half a century ago, when the parasite was endemic across North America and northern Europe. (Tens of thousands of people were infected in outbreaks across the Netherlands and northern Germany after World War II.) In a strange twist, P. vivax was even used from the 1920s until the 1940s as a radical treatment for end-stage syphilis (see sidebar, p. 686). The "malariotherapy" practitioners recorded and published clinical data on hundreds of patients, documenting the behavior of different strains and the clinical course of the disease. Vivax malaria "is one of the only diseases or infectious agents that we've forgotten more about than we've learned in recent years," says Nick White, a professor of tropical medicine at Mahidol University in Bangkok and the University of Oxford.

"We have a vivax research deficit," Feachem says. Although scientists discovered in the 1970s how to grow P. falciparum in the lab, there is still no system for culturing P. vivax for more than a few weeks. It has even been unclear just how many people P. vivax sickens and where the toll is the highest. Malaria cases are notoriously hard to count, because they occur overwhelmingly in regions where health care—and health care records—are lacking (Science, 15 June 2012, p. 1372). And not all diagnostic tests distinguish whether a patient is suffering from vivax or falciparum malaria.

To help fill the gap, the Malaria Atlas Project, which Hay coordinates, has used geographic, population, and epidemiological information to estimate the number of people at risk of contracting P. vivax (Science, 6 August 2010, p. 618). Their latest analysis concluded that 2.5 billion people are at risk, which means they are living in places where the parasite has been reported and where mosquitoes can transmit it.

Most of those are in Asia and Latin America. Although P. vivax used to be entrenched in Europe and the United States, it disappeared as countries became wealthier and housing conditions improved. (One of the most effective, though expensive, antimalaria measures is mosquito-proof housing with screens on the windows and doors.) Now, it is a plague of low- and middle-income countries, except those in sub-Saharan Africa, where the P. vivax map has a conspicuous hole. There, most of the population lacks the Duffy antigen, a protein on the surface of red blood cells that P. vivax uses to invade the cells. The parasite can't spread effectively in populations in which most people are "Duffy-negative."

P. vivax is carried by at least 71 species of mosquitoes, which gives it another edge over P. falciparum. Many vivax vectors live happily in temperate climates—as far north as Finland. Some even prefer to bite outdoors or during the daytime, so in some regions indoor insecticide spraying and bed nets are less effective at preventing the disease. Several key vector species haven't ever been grown in the lab for closer study, and it's also unclear how widespread insecticide resistance might be.

One bright spot is that, like falciparum malaria, vivax malaria is treatable. In fact, P. vivax has so far developed less resistance to common drugs. Chloroquine, which has lost most of its potency against P. falciparum, can still effectively treat acute infections of P. vivax in most regions.

But those treatments are powerless against the parasite's nastiest trick: its ability to lurk in the liver, making it much harder to cure than P. falciparum. Both parasites, when they are transmitted from mosquito to human host, go first to the liver. But unlike P. falciparum parasites, which undergo asexual reproduction in the liver and then burst out to infect red blood cells, some vivax parasites simply go into hiding. They form what are called hypnozoites (the name derives from "sleeping parasites"), an especially small form that nestles inside a liver cell. There they remain for weeks, months, or even years, waiting until chances are good that a recipient mosquito will be available to pass sexual stages on to the next victim. In fact, it is the hypnozoites that allow the parasite to survive in more temperate zones, where mosquitoes bite only part of the year. The parasite can bide its time for 9 months or even longer—enough time to wait out the winter and allow new vectors to hatch. (Another parasite, Plasmodium ovale, can also form hypnozoites, but it is much rarer than P. vivax.)

Hypnozoites can't be detected by blood tests, so the best strategy to eliminate the parasite from a region would be to mass-treat populations with a drug that could kill the sleeping pathogens. One drug can do that: Called primaquine, it was developed in the 1940s and early 1950s. It has two major drawbacks, however. The standard dose requires people to take a daily pill for 14 days—not an easy thing to enforce in people who don't feel ill. And in people who have a genetic condition called G6PD deficiency, the drug causes red blood cells to burst open. In severe cases, the reaction, called hemolysis, can be fatal.

G6PD stands for glucose-6-phosphate dehydrogenase, an enzyme that is especially important in red blood cell metabolism. There is no cheap, easy field test for G6PD traits, so any mass treatment campaign risks severe side effects in some people. The variant also seems to confer some protection against vivax malaria, so that regions in which the parasite is common tend to have more people with the trait.

Another complication is that the drug itself is not well understood. No one knows how the body processes it or how it attacks the hypnozoite. The standard 2-week dose stems from the 14 days it took to ship malaria-infected soldiers home from the Korean War. Studies have shown that people treated with the drug have fewer relapses, but there is little definitive data on dosage, efficacy, or resistance.

Hopeful glimmers

An improved, if imperfect, alternative is raising hopes. At the annual meeting of the American Society of Tropical Medicine and Hygiene in Washington, D.C., next week, researchers are scheduled to present results from a long-awaited trial of what could be the first new drug to target liver-stage parasites in half a century, tafenoquine. Its main advantage: A single dose, instead of a 14-day course, seems to be sufficient. That "would be a game-changer," Newman says.

Tafenoquine was developed by researchers at the Walter Reed Army Institute of Research in the 1970s and tested, decades ago, in safety trials in thousands of healthy volunteers. It languished, however, until the push for malaria elimination sparked new interest in alternatives for primaquine, says Tim Wells, chief scientific officer of the Geneva-based nonprofit Medicines for Malaria Venture (MMV), which is helping coordinate the trial with the pharmaceutical company GlaxoSmithKline (GSK). In 2011, the partners launched the trial testing the effectiveness of a single dose of tafenoquine compared to a standard course of primaquine in 320 malaria patients in Brazil, India, Thailand, and Peru. (The drugs were combined with a standard 3-day course of chloroquine to treat blood-stage parasites.)

Although GSK scientists can't talk about the study before the meeting, initial trial results posted on the company website indicate that 90% of patients who received a single 300- or 600-mg dose of the drug were relapse-free 6 months later. Among patients who received primaquine, 24% relapsed within 6 months. "The data are absolutely spectacular," Wells says. Ideally, he says, researchers will be able to combine the safety data from the Army's earlier trials with the new study in a submission to the U.S. Food and Drug Administration for approval.

Tafenoquine is chemically similar to primaquine, so it still causes hemolysis in people who are G6PD deficient. Wells says GSK will apply for its approval only in combination with a test for G6PD deficiency. That could limit its use in some regions. Still, Newman says, a single dose is a huge improvement over a 14-day course of drugs. If the results hold up, he says, "tafenoquine will fix a lot of things."

Although other antihypnozoite drug candidates are sparse, the search for alternatives is gaining momentum. In 2008, the first P. vivax genome was sequenced. Since then, several more strains have been added to the databases, allowing researchers to identify new potential weak spots. Primate models and new ways to grow the parasite in vitro are also helping researchers search for new compounds that can target the parasite's liver stages.

Sangeeta Bhatia, a bioengineer at the Massachusetts Institute of Technology in Cambridge, has developed a way to grow human "microlivers," liver cells growing together with supporting cells that can live in the lab for 4 to 6 weeks. In July, Bhatia and her colleagues described in Cell Host & Microbe how they were able to grow liver stages of both P. falciparum and P. vivax. The researchers saw miniature forms of the parasite in some of their vivax cultures, which may be hypnozoites. The scientists did not see any of the small forms reactivate, Bhatia says, so they haven't yet proven that they have cultured hypnozoites, but she and others think it is likely. "We have a glimpse of the organism for the first time in vitro," she says.

Despite the challenges, Feachem says he is optimistic that with new attention to P. vivax, the parasite can ultimately be defeated, even in tropical regions where it seems hardest to tackle. He points to Taiwan, Singapore, and the Maldives as places that, with sufficient investment, managed to eliminate the parasite with existing tools.

A century ago, malaria "was a global disease. It was endemic in every country … including regions north of the Arctic Circle," Feachem says. More than 100 countries have eliminated malaria in the past century, he says; all of them overcame vivax. To be sure, he says, many of those victories were closely linked to economic development. Still, he says, "we've won this war 100 times in the past 100 years. It's not like we can't do it."

5. Malaria as Lifesaving Therapy

1. Gretchen Vogel

In the pre-antibiotic era, vivax malaria was used to treat patients dying of syphilis, allowing many to make nearly full recoveries.

Vivax malaria was once familiar to doctors not only as a foe, but also as an ally. In the first half of the 20th century, people with tertiary syphilis, the phase of the disease in which Treponema pallidum bacteria attack the brain and nervous system, were doomed to a gruesome death: They would become increasingly neurotic and gradually paralyzed. Most were institutionalized, and there was no cure.

So physicians drew on a theory that had gained prominence in the late 19th century—that high fever could help cure a variety of mental illnesses. Austrian psychiatrist Julius Wagner-Jauregg was one of the idea's strongest proponents, but his initial experiments in the 1880s with fever-inducing pathogens and compounds such as tuberculin and salmonella toxin failed. He reasoned that the fevers they induced were not severe enough. In 1917, he tried again when a soldier who had caught malaria while fighting in the Balkans was admitted to his ward. Wagner-Jauregg used the soldier's blood to inoculate nine neurosyphilis patients. Six of them got better.

Soon, malariotherapy was seen as a miracle cure. It became a leading treatment for end-stage syphilis, quickly spreading across Europe and North America. Between 1917 and the rise of penicillin in the 1940s, tens of thousands of syphilis patients were infected with malaria. Different clinics used different parasites, but "after a few costly mistakes" with Plasmodium falciparum, a more lethal parasite, "most people settled on vivax," says Nick White, professor of tropical medicine at Mahidol University in Bangkok and the University of Oxford in the United Kingdom.

No one is sure exactly how it worked, but the high fevers that resulted seemed to help the patients' immune systems fight off the bacteria. Roughly half recovered enough to resume normal activities; many were able to resume independent lives. In 1927, Wagner-Jauregg won the Nobel Prize in physiology or medicine for his discovery. (The Austrian's legacy has a darker side as well. He was an advocate of eugenics, and in the 1930s he was a Nazi supporter.)

Because of malariotherapy, "the parasite's biology was investigated in amazing detail," White says. The result was a wealth of information about the disease process and how it differs depending on the strain of P. vivax. Those records are gaining some new attention today, as vivax starts to emerge from the shadow of its better-known cousin, falciparum (see main text, p. 684).

But this medicinal use of the parasite is in part to blame for the later neglect of the disease it causes, says Kevin Baird of the Eijkman Oxford Clinical Research Unit in Jakarta. Because doctors used P. vivax as a medical treatment, he says, many people assumed that it must be relatively harmless. But Baird says that even at the height of the therapy's use, that reputation was unfounded: Although malariotherapy saved lives, it also killed as many as 15% of the patients who received it, despite close monitoring and treatment of the infection.

6. Climate Change

In the Hot Seat

1. Richard A. Kerr

Scientists pressed on global warming's link to weather disasters are scrambling to grasp the teachable moment without going beyond their meager understanding.

Many climate scientists winced earlier this year when a well-meaning nonscientist tried to use extreme weather to argue that global warming is real. "We can choose to believe that Superstorm Sandy, and the most severe drought in decades, and the worst wildfires some states have ever seen were all just a freak coincidence. Or we can choose to believe in the overwhelming judgment of science—and act before it's too late."

That was President Barack Obama in his State of the Union address. The fact is, there is little or no evidence that global warming steered Sandy into New Jersey or made the storm any stronger. And scientists haven't even tried yet to link climate change with particular fires.

Representative Lamar Smith (R–TX), one of the president's political opponents, got it just as wrong in a recent newspaper editorial titled "Extreme weather isn't linked to climate change." In fact, it is, sometimes. Climate models have securely linked several heat waves to global warming, which can increase the odds of extreme heat many fold.

For climate scientists, extreme weather is risky territory. There is no question that global warming is real, but the science linking any one hurricane, drought, or flood to climate change is shaky, at best. And yet politicians, the public, and the rare scientist inevitably seize on vivid, easy-to-grasp weather events to make their points about abstract, long-term climate. Add in the loud voices of climate activists like Al Gore and 350.org's Bill McKibben, and the climate change discourse is "as much politics as scientific evidence," says climate scientist Martin Hoerling of the National Oceanic and Atmospheric Administration (NOAA) in Boulder, Colorado.

But climate researchers aren't giving up on turning extreme weather events into moments of teachable science. September's mammoth international assessment from the Intergovernmental Panel on Climate Change (IPCC) (Science, 4 October, p. 23) details current understanding—such as it is—of extreme weather's links to climate change, and describes new methods for gauging those links. With more effort, climate scientists could one day answer the "Is this climate change?" question on the spot.

Where's the science?

For better or worse, extreme weather is persuading Americans to take global warming seriously. In March and September 2012, for example, climate and media researcher Anthony Leiserowitz of Yale University with his Yale and George Mason University colleagues surveyed more than 1000 Americans (http://tinyurl.com/l697t4o). In September, 74% of those polled agreed that "global warming is affecting weather in the United States." That was up by 5% from March, after a summer of record drought, high temperatures, and powerful storms. And substantial majorities said global warming had worsened every one of six recent extreme weather events in the United States—from high temperatures to forest fires to a blustery "derecho."

The public perception is that "we live on a new planet of extreme weather," notes communication researcher Matthew Nisbet of American University in Washington, D.C. "That's a very engaging narrative."

But it is one that makes many mainstream climate scientists uneasy. As summarized in a full-page table in the IPCC report, their confidence linking the observed global warming to extreme weather does not extend much further. There "very likely" have been fewer cold and more frequent hot days and nights since 1950, the report concludes, and humans "very likely" contributed to the changes. In a physically straightforward next step, the report finds that heat waves have become more frequent, longer, or both. And heavy precipitation events have become more frequent because warmer air can hold and then release more moisture.

But when it comes to the role of human-induced change in phenomena that are more than one step removed from a simple warming, the IPCC typically has "low confidence." That goes for droughts (down from medium confidence in the 2007 assessment), floods, and tropical storms. Wildfires aren't even considered, for good cause. It's plausible that a warming climate plays a role in fires in places like the western United States and Australia, says wildfire researcher Max Moritz of the University of California, Berkeley. But "fire is a couple steps removed from temperature or precipitation, and our records are short. So detecting a trend is tough and attributing an event to climate change is really, really tough. We have to be very careful."

Wrong messengers

Links between extreme weather and climate change are not only often scientifically suspect, they may also be a risky strategy for persuading the public to take climate change seriously. "What disturbs me is assigning anything that comes along to global warming," says professor emeritus of meteorology John M. Wallace of the University of Washington, Seattle. "That may work in the short run, but I don't think that kind of conversion has staying power." Indeed, surveys coming out on the 1-year anniversary of Hurricane Sandy's landfall (29 October) show the concerns about hurricanes that spiked in the wake of the disaster have nearly faded away.

And "there's a little bit of 'live by the sword, die by the sword' " in making the connection, Leiserowitz says. A steady stream of extreme weather events makes for a steady media drumbeat on climate change, but that stream can falter. The current Atlantic hurricane season looks to be a near no-show with just two short-lived, minimal hurricanes (Category 1) so far with a month to go in the season and nothing stirring in the tropical Atlantic. And no major hurricane (Category 3 to 5) has struck the U.S. coast since 2005. (Sandy may have been a "super" storm, but it wasn't a major hurricane.)

When the weather turns cold, it becomes a cudgel for climate skeptics. The "Snowmageddon" that hit Washington, D.C., in February 2010 with 70 centimeters of snow brought out a less-than-playful taunt from conservative U.S. Senator James Inhofe. His grandchildren and their parents built a much-photographed igloo with a sign reading "Al Gore's New Home." Actually, Inhofe's taunt was baseless; global warming favors heavier precipitation, both wet and white.

Indeed, the whole field of extreme weather is a minefield for scientists. "Extreme events are the last place you want to look to document the human effect" of climate change, notes science policy scholar Roger Pielke Jr., of the University of Colorado, Boulder. Uncertainties and unknowns are so abundant in the field that "I've advocated for a long time that extreme events should not be part of the public dialogue," he says.

Try, try again

As long as reporters and the public insist on blurring climate change and run-of-the-mill weather, however, experts must manage as best they can. At the nonprofit Climate Central in Princeton, New Jersey, scientists and journalists work with the public's go-to people on weather: local TV meteorologists. "In these moments [of extreme weather], people have questions, we provide the context," says Climate Central's chief climatologist, Heidi Cullen. "Sometimes it's a little bit messy, but we try to be really, really careful. We educate people about the scientific method itself."

Climate scientists are also working on developing better talking points. "I talk about the risk," says climate scientist Peter Stott of the U.K. Met Office's Hadley Centre in Exeter. "Sometimes it has been quite successful. People understand there's always been extreme weather." By consulting climate records and modeling extreme events with and without added greenhouse gases, scientists can talk about how much global warming has increased the chances of extreme events—without blaming any one event on warming. For example, a NOAA and U.K. Met Office study published in the July 2012 Bulletin of the American Meteorological Society found that heat waves like the one that scorched Texas in 2011 are now 20 times as likely to occur as they were 50 years ago given the same conditions in the tropical Pacific that favor them.

That message came a year after the heat waves—fast for a meteorological study, but too slow to influence public perceptions. But Myles Allen thinks modelers can forge links between global warming and particular extreme weather much faster. Allen, a climate scientist at the University of Oxford in the United Kingdom, says models used to forecast the next season's climate could be adapted to calculate the probability of a range of extreme events. "It wouldn't be all that difficult, though it would require substantial funding," Allen says, "but we should do it." Then, when the first reporter calls in the midst of the next heat wave, there might be a firmer answer to that nagging perennial question.