# News this Week

Science  20 Apr 2012:
Vol. 336, Issue 6079, pp. 280
1. # Around the World

1 - Beijing
A New Uproar Over Chinese
2 - Zagreb
Director of Key Croatian Research Center Ousted
3 - Bering and Okhotsk Seas
Monitoring Seals From On High
4 - Washington, D.C.
New Biodefense Lab in Limbo
5 - Beijing
Cleaning Up China's Journals

## Beijing

### A New Uproar Over Chinese Tobacco Research

A tobacco research project nominated for China's 2012 National Science and Technology Progress Award has produced an uproar among China's scientific community.

The project, titled “Formulation and Application of a Theoretical System for Chinese Cigarettes,” was nominated by the State Tobacco Monopoly Administration. The cited achievements include improving quality and marketability of Chinese cigarettes and new sales revenue of about $27.5 billion over the last 3 years. Yang Gonghuan, a professor at Peking Union Medical College's School of Basic Medicine, published an open letter to science minister Wan Gang on 3 April calling on the Ministry of Science and Technology (MOST) to ban tobacco research from being considered for national science awards. Editors at China's foremost science Web site and blog, ScienceNet.cn, began collecting signatures on 8 April from readers opposed to cigarette research's consideration for a science award. Tobacco research has garnered increased criticism in China: Last year, researchers protested the election of tobacco scientist Xie Jianping to the prestigious Chinese Academy of Engineering. Xie's low-tar research had received the National Science and Technology Progress Second Prize three times: in 2003, 2004, and 2010. http://scim.ag/Chinatobacco ## Zagreb ### Director of Key Croatian Research Center Ousted The head of one of Croatia's most important natural sciences institutes has lost her job. The official reason for the dismissal of Danica Ramljak, a medical researcher who took the helm of the Ruđer Bošković Institute (IRB) in Zagreb in 2009, is that she does not qualify as a “research associate/fellow” under Croatian law. Ramljak, however, claims she's being punished for revealing corruption at the institute. She says that after she took over, she discovered several “large financial embezzlements” in past projects. At her invitation, police and Croatia's state attorney started an investigation at the institute in 2010, which was already under investigation by the Ministry of Finance's tax administration. In December 2011, a report by the tax administration concluded that IRB had failed to pay around$1.3 million in taxes as a result of various illegal activities by its scientists in 2008.

Croatia's science minister, Željko Jovanović, says he appointed a new management council in February to bring “stabilization” to the institute, and supported the conclusion that Ramljak did not meet formal requirements to head the institute in an 8 March letter to the council. http://scim.ag/Ramljak

## Bering and Okhotsk Seas

### Monitoring Seals From On High

Last week, a group of scientists boarded equipment-laden airplanes, braved freezing temperatures, and began a massive accounting of seals in the Arctic. The project, which includes American and Russian scientists, is a 2-year effort aimed at understanding ice-associated seal populations in the Bering and Okhotsk seas.

Bearded (Erignathus barbatus), ringed (Phoca hispida), spotted (P. largha), and ribbon seals (Histriophoca fasciata) use springtime on the ice to give birth, mate, or molt—which makes it an ideal time to count them. The team plans to use a combination of thermal imaging and digital photographs to conduct their census.

“It's pretty widely anticipated that [the seals'] habitat will change over the next decade to centuries,” says project leader and marine mammalogist Peter Boveng of the National Oceanic and Atmospheric Administration in Seattle, Washington. And getting a good handle on their population sizes is essential to any potential conservation efforts, he adds.

## Washington, D.C.

### New Biodefense Lab in Limbo

The United States faces a stark choice between funding a new state-of-the-art laboratory for agricultural biodefense and paying for ongoing research on the topic, according to the government's top biosecurity research official.

“We are hard up against it now; you can't do research without modern facilities, but the money for modern facilities comes out of the same piggy bank that pays for research,” Tara O'Toole, head of the Department of Homeland Security's (DHS's) Science and Technology Directorate, told a new study panel of the U.S. National Academies' National Research Council (NRC) on 13 April. DHS has asked the panel to examine plans for the proposed National Bio and Agro-Defense Facility (NBAF) in Manhattan, Kansas, which could cost $1 billion and is supposed to replace the aging Plum Island Animal Disease Center in New York. But funding issues and opposition to NBAF (Science, 24 February, p. 903) have prompted the Obama Administration to consider canceling or scaling back the laboratory. The NRC panel expects to release its recommendations by the end of June. http://scim.ag/biodef ## Beijing ### Cleaning Up China's Journals In what the Chinese press dubs a “war to protect academic honesty,” publishers of more than 1000 journals have pledged to root out plagiarism and falsified research. The publishers, heads of journals under the China Association for Science and Technology, signed a pledge 10 April vowing to punish editors who misuse their positions or knowingly publish plagiarized papers. China's General Administration of Press and Publication is intent on tidying up the bloated academic publishing industry (Science, 21 October 2011, p. 301), and journal publishers may be feeling the heat. Problems reach beyond faked research to fake journals that turn out citations to pad scientists' resumes. At some publications, the review process is just a matter of “going through the motions,” the newspaper China Science Daily quoted former Mechanics in Engineering editor Li Jiachun as saying. Others contend that punishing editors won't solve a problem rooted in the severe publish-or-perish mentality in China. Some Chinese institutions even pay scientists top dollar for publishing in journals with high impact factors. Says Meng Zhao, development editor at Neural Regeneration Research: “This is an ethical issue not just for the researchers, but for the whole academic society.” 2. # Random Sample ## Noted For the second year in a row, Thomson Reuters named Eric Lander of the Broad Institute in Cambridge, Massachusetts, the year's most influential researcher. With 14 often-cited “hot papers,” Lander topped the list of 15 Hottest Researchers of 2011. Genetics is also on fire, according to the report: It was the primary field of study for seven of the 15 researchers. ## Counting Penguins From Space The hardest part of counting penguins isn't getting them to hold still; it's getting to the remote places where they live, especially Antarctica. Satellite images to the rescue: On 13 April, researchers reported the results of the first satellite image–based comprehensive study of penguins in PLoS ONE. To count the birds, the team enhanced the images with pansharpening, making it possible to distinguish between shadows, guano, and actual penguins. The team found twice as many emperor penguins (Aptenodytes forsteri) as were thought to exist—roughly 595,000. They also counted seven new colonies, bringing the total to 44. “This is a leap forward, but it doesn't change the conservation concern [about] emperor penguins and many other species,” says penguin expert P. Dee Boersma of the University of Washington, Seattle. “Unfortunately, with climate warming and variation, we are likely to be studying the decline of emperor penguins. Satellite mapping will allow scientists to determine where the declines are occurring and by how much.” ## By the Numbers 193—Number of papers co-authored by disgraced anesthesiologist Yoshitaka Fujii that journals may retract by 30 June. Fujii would hold the record for most retractions by a single author. 56—Number of coral species in U.S. waters that likely face extinction by 2100, according to a 16 April National Marine Fisheries Service review of 82 corals being considered for protection under the Endangered Species Act. ## ScienceLive Join us Thursday, 26 April, at 3 p.m. EDT for a live chat on the continuing science versus security debate sparked by two H5N1 avian influenza studies. http://scim.ag/science-live ## Not-So-Silly Putty for Potholes Non-Newtonian fluids are the stars of high school science demonstrations: Poured or pulled slowly, a gooey batter of corn starch and water, for example, will flow like a liquid, but when subjected to high stress, such as being hit firmly or pulled sharply, it becomes stiff like a solid. Unlike Newtonian fluids, which maintain their fluid state regardless of disturbances, the viscosity, or resistance, of a non-Newtonian fluid changes in response to forces applied to it. Different non-Newtonian fluids—such as mayonnaise, ketchup, Silly Putty, and blood—all contain some sort of particle, and the interaction of those particles explains their behavior under stress. Those unusual physical properties gave a group of undergraduates at Case Western Reserve University in Cleveland, Ohio, an idea: Design a non-Newtonian fluid to fill potholes. “When there's no force being applied to it, it flows like a liquid does and fills in the holes,” says 21-year-old team member Curtis Obert, “but when it gets run over, it acts like a solid.” The team created a powdered mixture stored in waterproof bags designed to stand up to the salt and freezing conditions of a Midwest winter. City workers would add water and seal the bag. It's less messy than packing potholes with asphalt, Obert says, and dropping the fluid-filled bags into potholes requires little training or experience. When the roads are repaired, the bags can be removed and reused. The students devised the idea as part of an engineering contest sponsored by French materials company Saint-Gobain—and took first prize this month. They plan to patent their invention, so they won't divulge their exact formulation, but they say it's biodegradable and poses no danger to people or the environment. http://scim.ag/puttypotholes 3. # Newsmakers ## Three Q's During the 2011 Egyptian revolution, looters broke into the Museum of Egyptian Antiquities in Cairo and plundered storehouses at archaeological sites such as Saqqara. Last week, Mohamed Ismail Khaled, the Egyptian official in charge of foreign archaeological missions, spoke to a Yale University audience about the effects of the revolution. Science caught up with him there. Q:What challenges did you face during the revolution? We had many difficult times, beginning with what happened at the [Museum of Egyptian Antiquities]. The same wrong information was just multiplied by the media. People didn't believe us when we said that only 54 pieces were stolen from the museum and that now only 29 are missing. All the masterpieces relating to King Tut, thank God, they are back. Q:Are all foreign archaeological missions back in the field again? The only missions that left Egypt were from the Cairo area, and they left because it was not safe. But missions in the Eastern and Western Desert, in Aswan, and in other areas, they did not see the revolution. They never stopped working. Q:Egypt's former minister of state for antiquities affairs, Zahi Hawass, campaigned for the return of Egyptian artifacts, such as the Rosetta Stone, from foreign museums. Is this still a priority? It is our cultural heritage. We will not leave the repatriation issues unsettled. But the problem now is that the Ministry of State for Antiquities is suffering from internal protests: people want jobs, increases in salaries. You have to solve these problems first and then think about the fight outside the country. ## Exiled Chinese Physicist Fang Lizhi Dies Astrophysicist Fang Lizhi, who died at 76 on 6 April, was a champion of freedom, human rights, and democracy in China. Fang began his academic career as a physics lecturer in 1958 at the University of Science and Technology of China (USTC) in Beijing, but his career was interrupted by compulsory labor on farms and in a coal mine during the Cultural Revolution. In 1976, Fang resumed publishing academic papers, and was elected at age 44 to the Chinese Academy of Sciences's Division of Mathematics and Physics in 1980. In 1984, he was appointed vice president of USTC. Fang called for political reform during the 1980s. In 1987, Deng Xiaoping, China's paramount leader, ordered Fang's removal as USTC vice president. The government labeled Fang a “black hand” behind student demonstrations that ended in a bloody crackdown in June 1989. Fang and his wife were eventually allowed to leave China, and in 1992 Fang joined the faculty at the University of Arizona in Tucson. He was elected a fellow of the American Physical Society in 2010 for “his important work in cosmology and early-universe physics … and his tireless, self-less, courageous and continuing advocacy of human rights in China.” http://scim.ag/FangLizhi 4. Hydropower # Trouble on the Yangtze 1. Jane Qiu* Upriver habitats—including a critical refuge created when construction began on the Three Gorges Dam—are now at risk from a series of new projects. YONGSHAN, CHINA—Among the hundreds of fish species that call the upper Yangtze River home is the largemouth bronze gudgeon. The species spawns in the rapids of this rocky waterway—also known as the Jinsha River—which descends from the Tibetan Plateau through the mountains of western China. Its eggs and larvae are kept afloat by the swift current until they hatch and mature hundreds of kilometers downstream. “They have evolved to live in fast-flowing rivers,” says Cao Wenxuan, an ecologist at the Institute of Hydrobiology at the Chinese Academy of Sciences (CAS) in Wuhan. But with dozens of new dams planned for the Yangtze system, that habitat will soon change. Last month, preparatory work began on the controversial Xiaonanhai Dam, with more projects to follow. Within a few years, the Jinsha will slow to a sluggish pace and its temperature will drop as a series of large dams release cold bottom water from their reservoirs into the river. Along with other endemic fish species, the largemouth bronze gudgeon may spawn up to 3 months later, and soon after, its eggs and larvae may sink to the bottom and die from lack of oxygen. For species already threatened by the Three Gorges Dam downriver, Cao says, the new series of hydropower dams will “take away their last refuge.” Last year, the central government solidified plans to increase China's reliance on non–fossil fuel energy from the 2010 level of 8% to 15% of the energy mix by 2020. Nearly two-thirds of that target will come from hydropower—an increase on par with adding nearly one Three Gorges Dam a year. “The scale of hydropower development in China is simply off the charts,” says Edward Grumbine, an environmental policy researcher at CAS's Kunming Institute of Botany in Yunnan Province. Ecologists say China's hydropower push will threaten already-taxed ecosystems in the upper Yangtze. Central to the spurt of construction is a 770-kilometer-long stretch of the lower Jinsha River flowing through Sichuan and Yunnan provinces. Last June, China announced an injection of$63.4 billion for hydropower in the region to cover four massive dams with a total capacity of 43,000 MW. “It's worrying to see so many proposed large dams, one immediately after another,” says Zhang Xiaodong, deputy director of the China Earthquake Networks Center in Beijing.

In addition, three large dams are under construction and five are planned on the 560-kilometer-long middle Jinsha, with more planned for the 960-kilometer-long upper reach. At a combined height of 2 kilometers, the dams will convert “the rapidly flowing Jinsha River into a series of stepped lakes with few free-flowing sections,” says Liao Wengeng, deputy director of the National Research Center for Sustainable Hydropower Development (NRCSHD) in Beijing. Also tagged for development are Yangtze tributaries such as the Yalong, Min, and Dahu rivers.

As construction of the Three Gorges Dam got under way in the 1990s, ecologists submitted petitions to the central government calling for an upstream reserve to protect fish populations. The result was the Upper Yangtze River Rare and Endemic Fish Reserve, a 500-kilometer-long protected stretch of river that includes 350 kilometers of the Yangtze mainstream. The reserve became a critical habitat for some 190 fish species—including the critically endangered paddlefish and the Yangtze sturgeon (Science, 1 August 2008, p. 628).

In 2005, officials sliced off 150 kilometers of the upriver portion to make way for the Xiangjiaba and Xiluodu dams. Now the Xiaonanhai Dam will chip away at the reserve even further. At a cost of \$3.8 billion, the dam is expected to generate 1750 MW of electricity at its completion. Officials in Chongqing, the municipality overseeing the project, say that it will alleviate power shortages and boost the local economy. But it will also create a nearly 100-kilometer-long reservoir in the heart of the upstream protected area.

For years, ecologists have voiced fierce opposition against the Xiaonanhai Dam. But the battle was lost last December, when China's State Council green-lighted Chongqing's request to shrink the reserve. Road building and other preparation began 29 March. Critics like Fan Xiao, chief engineer at the Sichuan Bureau of Geology and Mineral Resources in Chengdu, fear that Xiaonanhai will pave the way for two additional upstream dams proposed by Sichuan authorities in the reserve area. And that could mean the end for the paddlefish, the Yangtze sturgeon, and other endemic fish: “The reserve would exist only in name,” he says.

## Geological minefield

Driving on the narrow road clinging to a cliff above the Jinsha River is not for the fainthearted. It circles mountains that have risen out of tens of millions of years of thrusting and folding of Earth's crust, overlooking a steep valley carved by the roaring river. Scars left by recent landslides cut across facing slopes.

Critics fear that China's hydropower expansion will collide with this stark topography. Crisscrossed with active faults hundreds of kilometers long, the region is “much more geologically complex than the Three Gorges,” says geologist Guo Shunmin of the China Earthquake Administration's Institute of Geology in Beijing. Earthquakes of magnitude 7 or 8 are not uncommon. “A lot of the reservoirs will have active faults beneath them,” he adds.

Given that some evidence links construction of the Zipingpu Dam to the 2008 Wenchuan earthquake (see sidebar, p. 291), “there should be studies on the effect of water impoundment on active faults beneath the [Jinsha area] reservoirs,” says Hu Xianming, a geophysicist at the Sichuan Seismological Bureau's Institute of Reservoir-Induced Seismicity Research in Chengdu. The current safety evaluation, however, involves only surveys to avoid building dams on active faults.

Compounding the problem is the up to 2 meters in precipitation the Jinsha region gets every year. In monsoon season, torrential rains can tear apart steep slopes. Massive landslides have blocked the Jinsha for days at a time in the past, says Yang Yong, director of the environmental group the Hengduanshan Society in Chengdu.

Changes in water temperature will be stark as well. The 278-meter-high Xiluodu Dam will cool water temperature by an average of 1.5°C for the months of March through September, according to the project's environmental impact assessment (EIA). Deep reservoirs stratify water into layers of different temperature, with the coldest near the bottom. Water from the cold bottom layer will be released downstream, Liao says. Most fish species spawn in April or May, when the water warms to 16°C to 18°C. After the four dams on the lower Jinsha are built, the EIA says, downstream portions of the river won't reach such temperatures until 2 to 3 months later. That will “hamper fish reproduction,” Liao says. He points to the Three Gorges Dam: With spawning delayed by over a month, downstream carp populations have been decimated.

The problems brought on by that earlier dam are well documented. The river dolphin, or baiji, has been functionally extinct since 2007, and ecologists fear that the finless porpoise, or jiangzhu, may soon follow it.

Also of concern is silt accumulation: Sediment retention in the reservoir means the clearer downstream water can cut the riverbed deeper and lower water levels in lakes fed by the Yangtze. In January, Poyang Lake, China's largest freshwater lake, was hit by the worst drought in 6 decades: the water level dropped to a mere 8 meters, and much of the lake has become a plain of cracked mud. Such problems will snowball with “a cascade of upstream dams,” Liao says.

## A stacked deck

Some hydrologists say that optimizing dam operation could alleviate problems with downstream water supply. But many are unconvinced. With so many new dams, says Guo Qiaoyu, director of The Nature Conservancy's Yangtze River project, “it will be extremely difficult to ensure proper coordination between provinces and companies that operate the dams.”

With the new hydropower boom, criticism of China's EIA process is mounting. By law, dams cannot be constructed in nature reserves or their buffer zones. But the government is all too willing to redraw the boundaries to accommodate hydropower projects, some say. The Xiaonanhai Dam in particular, Guo says, is “yet another example of the country's disregard for the environment.”

Critics say EIA committee members are often paid for their services by dam projects and deliver favorable assessments in order to be invited back. “The EIA is just about friends evaluating each other's projects,” says Wang Mingna, a hydrologist at the Chinese Institute of Water Resources and Hydropower Research in Beijing. Scientists' warnings “often fall on deaf ears,” adds ecologist Yang Junxing of CAS's Kunming Institute of Zoology.

Adding bias to the schedule, ecologists say, are rules that allow developers to start preparing for a proposed dam while project assessment is still under way. And EIAs are too narrow, examining projects in isolation, points out He Daming, an ecologist at Yunnan University, Kunming. “Even if the impact of individual dams is acceptable,” he says, “the cumulative effects of stacking dams on top of one another could still be catastrophic.”

The science ministry is funding research that takes additive impacts into account. The Ministry of Water Resources, meanwhile, may soon improve the EIA process, says Yu Xuezhong, chief engineer at the NRCSHD.

But such measures may come too late for the upper Yangtze's beleaguered fish species. Ecologists are scrambling to set aside small sanctuaries—in small tributaries near their current habitats, for example. The goal, Cao says, is to “save as many fish species as we can. All we can hope for is to slow down the extinction rate.”

• * Jane Qiu is a writer in Beijing and London.

5. Hydropower

# Evidence Mounts for Dam-Quake Link

1. Jane Qiu*

Newly published studies present the strongest evidence yet for a link between the 2008 Wenchuan earthquake and the reservoir behind the 156-meter-high Zipingpu Dam.

CHENGDU—Ever since the devastating magnitude-7.9 Wenchuan earthquake killed 80,000 people in 2008, Chinese hydrologists and geologists have wrangled over whether the reservoir behind the 156-meterhigh Zipingpu Dam may be to blame (Science, 5 March 2010, p. 1184). Today, as China embarks on a spurt of new hydropower development (see main text, p. 288), the debate is getting increasingly heated. Newly published studies present the strongest evidence yet for the link.

Most scientists agree that the Wenchuan hypocenter, or depth of the initial rupture, is directly beneath the reservoir. But just how deep it lies is in dispute. The China Earthquake Networks Center (CENC) and geophysicist Liu Qiyuan of the China Earthquake Administration's (CEA's) Institute of Geology in Beijing calculate the hypocenter at 14 and 19 kilometers beneath the surface, respectively. At such depths, some scientists contend, water from the reservoir could not have reached the fault.

Others point out that Liu and CENC based their calculations on seismic data from stations tens of kilometers from the epicenter. Using data from the Zipingpu seismic network, including one station almost directly above the hypocenter, Xu Xiwei, deputy director of CEA's Institute of Geology, and colleagues reported last year in Seismology and Geology that the hypocenter is as shallow as 6 to 9 kilometers—within easy reach of water from the reservoir.

Some scientists also point to numerical modeling studies looking at stress changes caused by the weight of the reservoir and water infiltration. Xinglin Lei, a geophysicist at the Geological Survey of Japan in Tsukuba, concluded in a study published in the Journal of Asian Earth Sciences last year that the reservoir significantly impacted the Beichuan-Yinxiu fault, which runs along the reservoir, and increased the stress on the hypocenter of the Wenchuan Earthquake. That could hasten the occurrence of the earthquake by tens to hundreds of years, he argues. Shemin Ge, a hydrogeologist at the University of Colorado, Boulder, and colleagues came to a similar conclusion using a different model in an earlier study.

That finding was contradicted in 2010 studies by geophysicists Zhou Shiyong of Peking University in Beijing and Kalpana Gahalaut of the National Geophysical Research Institute in Hyderabad, India. But their results could be explained by the use of different numerical models and geometrical parameters for the faults, among other factors, says Jian Lin, a geophysicist at Woods Hole Oceanographic Institution in Massachusetts, who is not involved with any of the studies.

The strongest evidence for a Zipingpu-Wenchuan link may come from analyses by Xu's team of nearly 1000 seismic events recorded by the Zipingpu seismic network between August 2004 and May 2008, before the Wenchuan quake. The researchers found three clusters of seismicity—all under magnitude 3.5—after the reservoir was filled with water in September 2005. One, the Shuimo swarm, occurred along the Beichuan-Yinxiu fault, where the researchers concluded it was induced by the reservoir.

Despite the controversies, many Chinese geophysicists now agree that the reservoir may be connected to the Wenchuan earthquake. Even if the hypocenter lies 19 kilometers below the surface, Liu says, as his calculation shows, this doesn't exclude the possibility that Zipingpu hastened the quake because “small incremental stress changes due to the reservoir could rupture critically stressed faults—even without water reaching them.”

The new studies highlight the need to consider reservoir-induced seismicity when building large dams in quake-prone regions, scientists say. With dozens of dams planned for the upper Yangtze, Ge says, “We need to assess whether the proposed reservoirs could significantly speed up the accumulation of stress and cause rock failures.“

• * Jane Qiu is a writer in Beijing and London.

6. American Chemical Society Spring Meeting

# Nanoparticles Offer ‘Open Sesame’ Keys to New Drugs and Vaccines

1. Robert F. Service

Research presented at the ACS meeting suggests that packing RNA strands together to form nano-sized particles could help get them into target cells and that another nanoparticle may lead to novel kinds of vaccines.

Drugs that rely on tiny strands of RNA to shut down the production of problem proteins have generated intense research interest in recent years. But they have to overcome a common difficulty: It's hard to get the RNA into target cells. Research presented at the meeting suggests there may be a straightforward solution: Pack the strands together to form nano-sized particles. And a second study indicated that a different kind of nanoparticle may lead to novel kinds of vaccines. Nano-medicine may be about to get a big boost.

A little over a decade ago, researchers demonstrated that it's possible to use short strands of RNA to knock down the expression of particular genes and prevent construction of key disease proteins. The RNA strands, called short interfering RNAs (siRNAs), are tailored to bind to target strands of messenger RNA (mRNA) that carry genetic instructions from the cell nucleus to the ribosomes, where proteins are built. The mRNAs then can't be translated into proteins by the ribosomal machinery. To do their work, however, siRNAs have to enter cells. The trouble is, says Chad Mirkin, a chemist at Northwestern University in Evanston, Illinois, because RNA is negatively charged, it is repelled by cell surfaces, which are also primarily negatively charged.

Mirkin reported that he and his colleagues have overcome this problem by packing hundreds of copies of siRNA strands into a tight ball. The RNA ball attracts the attention of numerous positively charged cell surface proteins called scavenger proteins, which bind to it. The complex is then engulfed into the cell, and the spherical siRNA particles are later released to sop up their mRNA targets. Mirkin reported that in cell culture studies, the particles readily entered 49 of 50 different cell types (with red blood cells being the only exception) and knocked down the expression of target mRNAs.

Working with Alexander Stegh, a brain cancer expert at Northwestern University's Feinberg School of Medicine in Chicago, Illinois, Mirkin's team then designed siRNA particles targeted to prevent the expression of key proteins involved in brain cancer. When they injected the particles into mice with brain cancer, 1% of the particles crossed the blood-brain barrier, which stops most drugs from getting into the brain, and increased the average life expectancy of the animals by 20%. The hope, Mirkin says, is that the technique will enable a new generation of oncology drugs to work against brain cancer, currently one of the most difficult families of cancers to treat.

It was “just luck” that the particles managed to cross the blood-brain barrier, Mirkin says. But Joseph DeSimone, a chemist at the University of North Carolina, Chapel Hill, says Mirkin's team has been far more than lucky. “This has the potential to pull the siRNA field out of the toilet,” DeSimone says.

At the meeting, DeSimone reported some heavy lifting of his own: using nanoparticles to make novel vaccines. DeSimone's group has pioneered a technique for making organic nanoparticles of almost any size, shape, and composition. Now the group has incorporated, in some cases, dozens of immunogenic fragments from pathogens such as influenza into nanoparticles. When the researchers injected mice with the particles, 30% to 40% of the particles were taken up by immune cells, compared with roughly 1% of normal vaccine compounds, and antibody titers against influenza and other diseases increased as much as 12-fold. Not only might the work lead to vaccines that are more effective and require fewer booster shots, DeSimone says, but it could also require far less of a given formulation, thus dropping their cost and making them more readily available.

Mirkin returns the favor, calling DeSimone's latest work “fantastic.”

7. American Chemical Society Spring Meeting

# Biofuels and City Air: A Marginal Effect

1. Robert F. Service

The first citywide air quality study of its kind, reported at the meeting, suggests that unless more than 26% of cars switch to biofuels, it will have negligible effect on air pollution.

If drivers switch from gasoline to biofuels, will it lessen the air pollution that shrouds cities around the world? Studies of auto emissions have indicated it might. But the first citywide air quality study of its kind suggests that unless more than 26% of cars make the switch, it will have negligible effect.

The new work, reported by Franz Geiger, a chemist at Northwestern University in Evanston, Illinois, grows out of a natural experiment that takes place every year in São Paulo, Brazil's largest city. São Paulo is home to 1.5 million flex-fuel cars capable of switching between using gasoline and 100% ethanol, made from fermenting sugar cane. Because virtually all gas stations in São Paulo offer both fuels, drivers of flex-fuel cars choose by calculating which will let them drive more cheaply, Geiger says. (Gasoline tends to be more expensive but also supplies about 30% more energy per liter.)

Unlike gas prices in the United States and Europe, which fluctuate with world oil prices, gas prices in Brazil are tightly regulated. The cost of ethanol, however, varies wildly with the cost of sugar cane. For most of the year, it's cheaper for drivers to fill up with ethanol. But for two of the past three winters, world hikes in the price of sugar have made gasoline a better value, prompting 1.5 million drivers—about 26% of the total of 5.8 million cars and light trucks—to switch for a couple of months.

Geiger and his colleagues, including Northwestern University economist Alberto Salvo, decided to see whether this change affected air quality. To their surprise, it didn't. Geiger reported at the meeting that they analyzed air sampling data taken at regular intervals every day from 22 stations throughout the city. The sampling tracked carbon monoxide, nitrous oxides, sulfur dioxide, ozone, and other compounds in both the high- and the low-ethanol seasons. But the researchers found no change in air quality. When they crunched the numbers further, performing numerous statistical regression analyses that attempted to isolate specific correlations with weather, traffic patterns, air-circulation patterns, and other possible links, they still saw no effect. “Any discernible change may require an even larger share of vehicles to switch fuels, or change to a new fuel altogether,” Geiger says.

Geiger stresses that a larger scale switch to biofuels might affect air quality. And air quality may still improve over time, as older, higher-polluting cars and trucks are replaced by newer, more-efficient models. That has yet to be seen. But the Northwestern team's new study will provide valuable baseline data to spot such a future trend, Geiger says.

Paul Alivisatos, director of Lawrence Berkeley National Laboratory in California, says the new results should be seen as “good news for biofuels.” The growth of sugar cane and other feedstocks removes carbon dioxide—the most abundant greenhouse gas—from the air, which is then returned to the atmosphere when the fuels are burned. Burning fossil fuels, by contrast, adds new CO2. And the new study, Alivisatos says, suggests that switching to biofuels doesn't carry a penalty in air quality, which on balance makes them a winner.

8. American Chemical Society Spring Meeting

# New Genetic Letters Augment DNA, and Soon Perhaps Life

1. Robert F. Service

At the ACS meeting, a pair of research groups reported that they now have synthetic nucleotides that can be incorporated into DNA and can be copied with near perfection by enzymes that copy natural DNA.

AGCT. The letters of DNA, along with their RNA cousins, write the code for all life as we know it. But perhaps not for long.

At the ACS meeting, a pair of research groups reported that they now have alternative letters—synthetic nucleotides—that can be incorporated into DNA and can be copied with near perfection by enzymes that copy natural DNA. These additions to the genetic alphabet are already enabling researchers to write new chemical functions into DNA, which could help usher in a wide array of biotechnology advances. And they are a critical step along the way to making semisynthetic life forms, written in the first new type of genetic code that life has ever known.

The effort to rewrite life's genetic code has a long history. Researchers have already created dozens of novel nucleotides, designated by initials such as P and Z, and they have even managed to incorporate many of them into natural DNA. But getting them to work in living, reproducing organisms is a tough challenge. One major problem is that when enzymes called DNA polymerases try to copy unnatural nucleotides, either they grind to a halt like a printer with a paper jam or they make mistakes.

Last year, Steven Benner, a chemist and founder of the Westheimer Institute for Science and Technology, a private research institute in Gainesville, Florida, and colleagues came close to solving that problem. He reported incorporating novel nucleotides into DNA and showed they could be copied with 99.8% fidelity. Still, 99.9% fidelity will be required to avoid mistakes building up in the new genetic code, or the replacement of novel bases by natural ones.

At the meeting, groups led by Ichiro Hirao of the RIKEN Yokohama Institute in Japan and Floyd Romesberg of the Scripps Research Institute in San Diego, California, reported the synthesis of new nucleotides that can be incorporated into DNA and copied with sufficient fidelity to work well in living organisms. Hirao and colleagues reported that their novel DNA was copied with as high as 99.97% fidelity. One limitation was that their new letters always had to be flanked by particular sequences of natural DNA to ensure high copying quality. Romesberg's team, meanwhile, got 99.9% fidelity with its system and showed that its novel letters could be incorporated anywhere in natural DNA strands without affecting the copying fidelity. Another group reports similar success with a different set of letters on page 341.

Now, the race will be on to get the new letters incorporated in living microbes. That won't be easy, Romesberg says.

Researchers still need to find ways to coax cells to import the new nucleotides or bring in the building blocks and assemble them once inside. They also need to show that the altered DNA is transcribed into RNA with corresponding novel letters and then translated into new amino acids that make up proteins. Researchers have previously coaxed cells to incorporate unnatural amino acids into proteins, but no one has yet started with novel genetic letters and gone the distance.

With several groups now zeroing in on that goal, life's genetic alphabet may soon be expanded for the first time.