News this Week

Science  02 Sep 2011:
Vol. 333, Issue 6047, pp. 1204
  1. Around the World

    1 - Hotan Prefecture, China
    Polio Returns to China
    2 - Washington, D.C.
    Webb Costs Rise to $8 Billion
    3 - Paranal, Chile
    Italy Lacks Funds to Interpret Data From New Telescope
    4 - McMurdo Station, Antarctica
    Icebreaker Deal to Keep Antarctic Research Afloat
    5 - Moscow
    Russia Postpones Manned Mission to ISS

    Hotan Prefecture, China

    Polio Returns to China

    After more than a decade without a case, China is grappling with an outbreak of wild poliovirus. The Chinese Ministry of Health confirmed the disease in four young children in Hotan Prefecture, Xinjiang province, in western China, who became paralyzed between 3 and 19 July. It's another major blow to the Global Polio Eradication Initiative (GPEI), which had hoped to stop wild transmission of the crippling virus by the end of next year.

    Genetic analyses have confirmed that the newly detected type 1 virus jumped the border from Pakistan, where conflict and inhospitable terrain have hampered efforts to vaccinate children. Cases in Pakistan have soared to 72 this year, up from 39 this time last year. Just 2 months ago, GPEI's Independent Monitoring Board warned that Pakistan's epidemic could jeopardize the entire global effort. China will launch an emergency campaign to vaccinate 4.5 million children in the immediate area in early September, according to GPEI.

    Washington, D.C.

    Webb Costs Rise to $8 Billion

    CREDIT: ESA/C. CARREAU

    There's no good time to announce a huge cost overrun for a major U.S. science facility. But even in a week that brought an earthquake and a hurricane to the nation's capital, the new $8 billion price tag for the 6.5-meter James Webb Space Telescope was a shocker. NASA's recalculation of the price doesn't include $780 million to operate the infrared observatory for 5 years. Under the revised plan, Webb would cost not only 23% more but would launch in 2018, 2 years later than previously scheduled.

    NASA is withholding details because the “replan” is under review by the White House Office of Management and Budget and may not be released until the president submits his 2013 budget request in February. Leaders in the astronomy community hope the White House will endorse both the higher number and a plan to share the fiscal burden between astrophysics and other branches of the $18 billion agency, rather than pummeling NASA's science programs. “To damage science for such a small contribution from the rest of the agency would not be very responsible,” says astronomer Garth Illingworth of the University of California, Santa Cruz. http://scim.ag/Webbcost

    Paranal, Chile

    Italy Lacks Funds to Interpret Data From New Telescope

    After spending €15 million to build a powerful survey telescope in Chile, Italy is scrambling to find the €250,000 a year needed to analyze the exquisite data that the telescope has begun to collect.

    The VLT Survey Telescope (VST) is the largest telescope in the world specifically designed to survey the skies in visible light. A joint venture between the Italian National Institute of Astrophysics and the European Southern Observatory, it began capturing its first pictures in June at a site adjacent to ESO's Very Large Telescope (VLT) in Paranal, Chile.

    Italy's investment has earned it 10% of the observation time now, and 20% starting in 2017. But Massimo Capaccioli, an astrophysicist at University of Naples Federico II and a champion of the VST program, says that time will go to waste if the government doesn't provide money for “at least four mathematicians and some computers” to process the data coming in. The project is no stranger to adversity: The original VST mirror was destroyed during delivery to Chile, and some of the telescope's mechanical parts also had to be rebuilt after they rusted during shipment. http://scim.ag/ItalyVST

    McMurdo Station, Antarctica

    Icebreaker Deal to Keep Antarctic Research Afloat

    The U.S. National Science Foundation (NSF) has agreed to pay a Russian company $8 million for the use of an icebreaker to cut a channel to resupply McMurdo Station in Antarctica, including the delivery of diesel fuel needed to support research throughout the continent.

    For the past 5 years, NSF has used the Swedish icebreaker and research vessel Oden, but in July the Swedish government decided to keep the ship at home next winter (Science, 19 August, p. 927). Unfortunately for Swedish oceanographers, its Russian replacement, the Vladimir Ignatyuk, is not capable of supporting research. And Finland will be leasing Oden for the next 5 years, adding to their suspicions that the government doesn't value polar research.

    NSF's contract allows it to hire the Ignatyuk for an additional two austral summers if it performs well this winter. That arrangement provides NSF with a backup in case the Polar Star, a heavy-duty icebreaker operated by the U.S. Coast Guard and now undergoing extensive renovations, is not ready in 2013–14. The fleet of three U.S. polar icebreakers hasn't been able to get the job done in Antarctica for nearly a decade. http://scim.ag/_icebreaker

    Moscow

    Russia Postpones Manned Mission to ISS

    A week after an unmanned Russian cargo craft carrying food and fuel to the International Space Station failed to achieve orbit and fell back to Earth on 24 August, Russia announced on 29 August that it would post-pone its next manned mission to ISS for at least a month to do safety checks.

    The loss of the cargo had little immediate impact, but a long-term consequence could be the temporary abandonment of ISS until scientists determine what went wrong with the Soyuz rocket that boosted the freighter into space. That rocket is similar to the Soyuz rocket that takes astronauts to the station.

    Three of ISS's six crew members are now slated to return to Earth on 16 September. Their replacements, originally set to launch on 22 September, now won't head to ISS until late October or early November.

  2. Newsmakers

    Three Q's

    On 1 September, Canadian-born volcanologist Donald Dingwell of Ludwig Maximilian University in Munich will become secretary general of the European Research Council (ERC). Dingwell, 53, will be the liaison between the ERC's Scientific Council and its Executive Agency. http://scim.ag/Dingwell

    Dingwell

    CREDIT: COURTESY OF THE EUROPEAN RESEARCH COUNCIL

    Q:What made you apply for this job?

    The ERC is by far the most exciting thing that has happened in the research landscape in Europe, possibly in the world, in the last decade. But … one has to be constantly on the watch for how these things develop. I'm happy to take that onto my shoulders for 2 years.

    Q:You don't have a lot of experience in European research policy.

    Not in making policy, no. But from the point of view of somebody who is impacted and makes use of the policy, yes. Twenty-five years of research in Europe, and I have been on over 20 panels. I have a lot of experience in the practicality of how these panels are run.

    Q:As secretary general for ERC, you will have few formal powers. Will that be a problem?

    I'm sure that when I walk into the building, it's not all going to be “Friede, Freude, Eierkuchen [peace, joy, egg pancakes].” I'm sure there will be friction points. My job is to communicate the wisdom of the council to the agency and to communicate the practicalities of the agency back to the council. But I know I have the support of all sides. How many times in life can you say that?

    Edison Liu Leaves Singapore To Head Jackson Lab

    Cancer researcher Edison Liu, 59, will be the next president of the Jackson Laboratory in Bar Harbor, Maine, the lab announced 26 August. Liu is leaving the Genome Institute of Singapore, where he has been executive director for nearly 11 years, since its founding. He's one of several high-profile scientists to depart Singapore recently (Science, 8 April, p. 165). Jackson Lab, a nonprofit organization that produces inbred mice and conducts research, is looking for ways to expand, and Liu says he is eager to help it do so. Although a proposed Jackson branch failed to launch recently in Florida, Liu argues that Jackson-West in Sacramento, California, has shown that new sites can make money and do excellent science.

    Liu

    CREDIT: JACKSON LABORATORY

    Liu received an M.D. from Stanford University in 1978; trained at the University of California, San Francisco; and taught medicine at the University of North Carolina, Chapel Hill. In 2001, Liu was running the 1200-person clinical sciences division of the National Cancer Institute in Bethesda, Maryland, when he was recruited to Singapore. Some of his important work has been on tyrosine kinase receptors, particularly the HER2 receptor, which affects breast tumors. http://scim.ag/EdisonLiu

  3. Random Sample

    British Mummies Are the Sum of Parts

    CREDIT: MICHAEL PARKER PEARSON/UNIVERSITY OF SHEFFIELD

    Talk about a tight community: According to DNA evidence, Britain's oldest mummies are actually “jigsaws” of body parts assembled from several individuals before being buried. The 3600-year-old mummies were discovered in 2001 in the prehistoric village of Cladh Hallan in Scotland by archaeologists from the University of Sheffield. Radiocarbon dating and analysis of bone mineralization suggested that the four people had been deliberately mummified in peat bogs and then reburied intact 300 to 500 years after their deaths, as some soft tissue was preserved that held the bones together.

    Puzzled by the unnatural position in which the mummies were curled, ancient DNA specialists at the University of Manchester took a closer look. By analyzing mitochondrial DNA, which is better-preserved than genomic DNA and is passed down from mother to child, the researchers recently discovered that the mummies were each constructed of parts from at least three different individuals who were not related on the maternal side. It's not yet clear why they were buried this way, but the archaeologists suspect it was ritualistic.

    Pathological Museum In Sore Trouble

    CREDIT: CHRISTOPH WEBER/BERLINER MEDIZINHISTORISCHES MUSEUM

    German pathologist Rudolf Virchow fathered three sons and three daughters. But his “dearest child,” he once said, was his vast collection of deformed fetuses and wax models of diseased organs. During Virchow's lifetime, he offered his collection—thousands of medical specimens and curiosities, including preserved brain tumors and stomach ulcers, skeletons, deformed organs, and knives used for bloodletting—as both a three-dimensional textbook for his medical students and a public museum. After his death in 1902, the collection remained available to the public as the Pathological Museum.

    But Charité, the Berlin Medical University, which made Virchow's collection the center of its Medical History Museum in 1998, has been in financial trouble for years—and is now toying with the idea of getting rid of the museum, which attracts 100,000 visitors a year but earns only a third of the €1 million it costs to run.

    “The museum is very important to us, but we have to significantly cut costs,” said Stefanie Winde, a spokesperson for the Charité. Among the options being considered are: give the collection to another museum, find a private sponsor to foot the bill, or simply close it down.

    A final decision will be made at the end of September, according to the Charité. Meanwhile, the deliberations continue to outrage many doctors and scientists. That public outcry has caught the Charité by surprise; they may have taken the title of a current exhibition about the history of nursing—titled “Who Cares?”—a bit too literally.

  4. Taking Stock of the Biodefense Boom

    1. Jocelyn Kaiser

    Ten years after the anthrax letters—and after billions of dollars of investment in labs and research—debate continues over how much safer the country is.

    SOURCES: NIAID; UNIVERSITY OF PITTSBURGH CENTER FOR BIOSECURITY; CLINICALTRIALS.GOV

    The anthrax mailings that petrified Americans soon after the 9/11 attacks a decade ago this fall, killing five people and sickening 17, led to an explosion of biodefense research in the United States. Nearly $19 billion has been spent—a huge increase over previous levels and about one-third of the entire $60 billion the country has put into biodefense preparedness. Although the influx of funds has yielded scientific insights and some new products, how much safer the country is as a result is a matter of debate.

    One concern is the expansion of high-containment labs. The country now has a dozen labs, eight more than in 2001, that will operate at biosafety level 4 (BSL-4), the highest security level for deadly pathogens such as Ebola virus. The National Institute of Allergy and Infectious Diseases (NIAID), which snagged most of the new research money, also used a chunk of it to build a host of major BSL-3 labs.

    Growth industry.

    Since 2001, the number of planned or operating high-security biosafety level-4 (BSL-4) labs in the United States has climbed from four to 12. The National Institute of Allergy and Infectious Diseases has also helped build 12 BSL-3 biodefense labs. Many more BSL-3 labs registered with the U.S. Centers for Disease Control and Prevention to work with select agents don't appear on this map (CDC doesn't release locations). But numbers (right) show the growth from 2004 to 2010 in registered labs, from 415 to 1495. The number of individuals approved through CDC to access select agents rose 42% to 11,825; as with BSL-3 labs, much of the increase was in academia.

    SOURCE: GAO-09-574 NIAID; CDC SELECT AGENT PROGRAM BACKGROUND CHECKS BY DOJ; NIAID

    Some of these facilities have encountered fierce local opposition. A $178 million NIAID-funded BSL-4 lab at Boston University sits unused, blocked by lawsuits from citizen groups concerned about safety. A Department of Homeland Security agro and biodefense BSL-4 lab being built in Kansas has also run aground over risk studies.

    Critics have questioned whether all these labs are needed, especially because no new attacks have occurred. They also worry that the proliferation of biodefense labs and workers has multiplied the risk that a pathogen will be accidentally or intentionally released. Those fears ramped up 3 years ago when the Federal Bureau of Investigation named Bruce Ivins, a researcher at an Army biodefense lab who committed suicide, as the likely perpetrator of the anthrax attacks. “We have created an opportunity for a repeat on a grand scale of the event that led to this explosion,” says Richard Ebright of Rutgers University in Piscataway, New Jersey, a critic of the biodefense expansion.

    Meanwhile, experts debate whether tighter biosecurity rules are increasing safety or ballooning costs and red tape and driving scientists from the field. And Ebright and others claim that NIAID's biodefense boom has diverted funds (and scientists) from bigger public health threats such as drug-resistant staph bacteria.

    Billions for biodefense.

    Most new money for biodefense research went to the National Institute of Allergy and Infectious Diseases (NIAID). As a result, NIAID's biodefense portfolio—now about $1.7 billion a year—soon eclipsed that of the Department of Defense, which until then had led federal efforts to develop bioweapons countermeasures. The Biological Advanced Research and Development Authority, which funds advanced development, came online in 2006. Altogether, the government has spent $19 billion on biodefense research since 2001.

    SOURCE: DOD AND BARDA DATA FROM FRANCO & SELL, BIOSECURITY AND BIOTERRORISM 9, (2 NOVEMBER 2011)

    As for research progress, some experts have concerns. The Strategic National Stockpile, intended to protect the nation in the event of an outbreak or attack, contains few new vaccines or drugs for pathogens other than smallpox and anthrax (see table). Critics have singled out the federal BioShield program (see p. 1216), but last year the National Biodefense Science Board suggested that NIAID shared some of the blame and recommended that the agency's biodefense portfolio should be better aligned with high-priority bioterrorism threats.

    But NIAID Director Anthony Fauci says filling the stockpile is not his institute's role. The agency has deliberately focused on fundamental areas, such as microbial sequencing and vaccine technology, that will also help address natural threats such as pandemic flu and SARS, he says.

    “People may say, ‘Wow, it's been 10 years, we've put approximately $15 billion into it, and we haven't been attacked by anybody. Is that money that has gone to waste?’” Fauci says. “The answer to that is a resounding no. Because what this has done for preparedness for any public health threat has absolutely been enormous.”

  5. Major U.S. Biodefense Labs

    Growth industry.

    Since 2001, the number of planned or operating high-security biosafety level-4 (BSL-4) labs in the United States has climbed from four to 12. The National Institute of Allergy and Infectious Diseases has also helped build 12 BSL-3 biodefense labs. Many more BSL-3 labs registered with the U.S. Centers for Disease Control and Prevention to work with select agents don't appear on this map (CDC doesn't release locations). But numbers (right) show the growth from 2004 to 2010 in registered labs, from 415 to 1495. The number of individuals approved through CDC to access select agents rose 42% to 11,825; as with BSL-3 labs, much of the increase was in academia.

    SOURCE: GAO-09-574 NIAID; CDC SELECT AGENT PROGRAM BACKGROUND CHECKS BY DOJ; NIAID
    Billions for biodefense.

    Most new money for biodefense research went to the National Institute of Allergy and Infectious Diseases (NIAID). As a result, NIAID's biodefense portfolio—now about $1.7 billion a year—soon eclipsed that of the Department of Defense, which until then had led federal efforts to develop bioweapons countermeasures. The Biological Advanced Research and Development Authority, which funds advanced development, came online in 2006. Altogether, the government has spent $19 billion on biodefense research since 2001.

    SOURCE: DOD AND BARDA DATA FROM FRANCO & SELL, BIOSECURITY AND BIOTERRORISM 9, (2 NOVEMBER 2011)
  6. Biodefense: 10 Years After

    Reinventing Project BioShield

    1. Jon Cohen

    The government's efforts to protect the public from bioattacks have been hampered by ongoing struggles to mesh military and civilian strategies.

    United statement.

    Project BioShield had wide support when President George W. Bush signed the bill into law.

    CREDIT: STEPHEN JAFFE /NEWSCOM

    In fall 2001, a few weeks after terrorists shook the world by flying commercial airliners into the Twin Towers, a second wave of attacks hit the United States. They caused far less harm but triggered powerful aftershocks of fear. Envelopes containing anthrax spores, sent to several news outlets and two U.S. senators, infected 22 people and killed five of them. Protecting against future bioterrorism attacks became a top priority for the government, and in his 2003 State of the Union address President George W. Bush announced the creation of Project BioShield. This “major research and production effort to guard our people against bioterrorism,” Bush said, would “quickly make available effective vaccines and treatments against agents like anthrax, botulinum toxin, Ebola, and plague.”

    Congress passed legislation to establish Project BioShield the next year, creating a special $5.6 billion fund for the Department of Health and Human Services (HHS) to entice the most qualified pharmaceutical and biotechnology companies to invest in products that otherwise had no commercial market. The flagship product, specifically singled out by Bush when he signed the bill into law at a White House ceremony, would be an improved version of the anthrax vaccine long used by the Department of Defense (DOD) to protect troops. Bush said HHS “has already taken steps to purchase 75 million doses” of this new vaccine, which the U.S. Army Medical Research Institute of Infectious Diseases had been developing for over a decade. The new version would have fewer side effects and be easier to administer. The White House said it expected the vaccine to become part of the Strategic National Stockpile (SNS)—a repository of medicines run by HHS's Centers for Disease Control and Prevention for use in a public health emergency—the next year.

    To this day, the SNS has no doses of a next-generation anthrax vaccine, nor any vaccines or drugs to defend against Ebola or plague. No major pharmaceutical companies have supplied Project BioShield, and the small biotech companies involved often have had difficulty with large-scale manufacturing and regulatory issues. Congress has also transferred $1.4 billion of BioShield money—more than 25%—to other projects. “What you're left with is a great idea that was terribly flawed and unfortunately didn't get the big splash it wanted,” says Robert Kadlec, a career U.S. Air Force officer who worked on biodefense for the George W. Bush White House and now is a director with the management consulting firm PRTM in Washington, D.C. “If this were a business and we ran it like in the private sector, we'd have been out of business a long time ago.”

    Project BioShield has delivered on some of its promises, making one-time purchases of drugs and vaccines that were already far along the development pipeline, and Kadlec and others emphasize that it has steadily improved over its 7 years of existence. It is also just one part of a massive post-9/11 scientific push to find and develop new medical countermeasures against chemical, biological, radiological, and nuclear threats. But taking stock of Project BioShield, many see an underlying tension that has bedeviled it from inception: HHS and DOD—the other main government agency that funds R&D to prepare the country for bioterrorist attack—have distinct needs, mindsets, and agendas. And HHS, the new rich kid on the block in the wake of 9/11 (see graph, p. 1214), has had some difficulty tapping DOD expertise and simultaneously charting its own course. “DOD and HHS have very different requirements,” says Michael Kurilla, who heads the Office of Biodefense Research Affairs at the U.S. National Institute of Allergy and Infectious Diseases (NIAID) in Bethesda, Maryland.

    Kurilla says the architects of Project BioShield, which was spearheaded by then–Vice President Dick Cheney, tried to adapt the DOD approach to protecting troops to the broader population: Vaccinate them against anthrax, smallpox, botulism, tularemia, and plague. “There was an expectation to vaccinate everyone in the country and take the biothreat off the table,” he says. But this ambitious goal gained little traction, both because the small companies that came forward stumbled in producing preventives and treatments and because HHS concluded that a program for the public had to take a different tack from the one for troops. “The initial focus and orientation for the program has changed dramatically,” Kurilla says.

    BioShield, take 1

    In a foretaste of the problems confronting Project BioShield, the national smallpox vaccination program for health care workers tanked in 2003, the year BioShield was launched (Science, 11 March 2005, p. 1540). The goal was to protect some 500,000 of these “first responders,” but the program attracted only 40,000 volunteers. For civilians, “taking the threat off the table” held little attraction when people weighed the risk of vaccine side effects against the perceived risk of a smallpox attack. The writing was on the wall: If the nascent BioShield emphasized prevention, it would face similar challenges.

    When Congress held a hearing that March about the proposed Project BioShield, experts flagged what they saw as another unrealistic aspect of the master plan. James Baker, an immunologist at the University of Michigan, Ann Arbor, who previously worked in the U.S. Army on its anthrax vaccine program, warned that the proposed project would likely attract only small companies with little experience, as the government had made no long-term commitment to continue purchasing any of the countermeasures after the initial investment. “No large pharmaceutical company is going to come in unless there's a defined market and a defined revenue stream that accompanies the contract,” Baker says today. He's disappointed but not the least surprised by what Project BioShield has accomplished. “We haven't moved as far as we thought we would have, given the time and money involved.”

    Cautious civilians.

    The national smallpox vaccination program's goal of immunizing a half-million health care workers fell far short.

    CREDIT: STEVE APPS/AP IMAGES

    Part of the problem, Kadlec says, is that from the outset BioShield didn't have sufficient funding. “Investing $5.6 billion for pharmaceutical and biomedical manufacturing is spit in the bucket,” he says, noting that it can cost up to $1 billion to develop a drug or vaccine.

    Project BioShield's f irst investment brought the dilemma painfully to the fore. HHS awarded $879 million—a huge chunk of its budget—to a fledgling biotechnology company, VaxGen, to make 75 million doses of a new anthrax vaccine. The decades-old anthrax vaccine, made from growing Bacillus anthracis and then isolating what's called protective antigen, must be administered in a half-dozen doses followed by annual boosters and causes many side effects. Since the 1980s, DOD had been working on a purer vaccine that contains a genetically engineered, recombinant version of protective antigen. But for a variety of technical, manufacturing, and funding reasons, the DOD project had stalled, and VaxGen—a company best known for an AIDS vaccine that had failed in human trials—acquired the technology and began developing its own version that promised to be safer and provide protection with three doses at most.

    Modest gains.

    BioShield added several vaccines and drugs to the Strategic National Stockpile, but critics expected more.

    CREDIT: SOURCE: HHS

    In December 2006, HHS canceled the VaxGen contract because the company had difficulty making a stable vaccine that met U.S. Food and Drug Administration (FDA) requirements for a planned clinical trial. “They had lots of inexperience in major things, including business, the ability to scale up a product, and the skills to deal with the regulatory pathway, which was nebulous in many areas,” says Robin Robinson, who at the time had recently taken over HHS's influenza and emerging disease program after a 12-year stint in the vaccine industry. “It nearly destroyed the program.” (VaxGen appealed the contract cancellation and later settled with HHS out of court.)

    Congress, well aware of Project BioShield's shaky start, passed legislation that same month that revamped the effort. A special HHS division, the Biomedical Advanced Research and Development Authority (BARDA), would now run the project. Modeled on a similar DOD division, “BARDA will bring innovation to a process that is simply too slow to combat terrorist activities or Mother Nature,” said the bill's key Senate sponsor, Richard Burr (R–NC). In addition to coordinating efforts to combat both bioterror and emerging infectious diseases, BARDA would fund earlier stage products and offer companies milestone payments to help them make it through the middle stage of R&D, the “valley of death” when many promising projects run out of funding. BARDA could also help companies scale up for commercial manufacturing and complete the testing needed for FDA approval.

    Bush signed the bill into law on 19 December 2006, the same day HHS canceled the VaxGen contract. Robinson's branch moved under BARDA, and in April 2008, he became its first director.

    BioShield, take 2

    Project BioShield's contributions to the SNS to date are modest; they include mostly products contracted before BARDA came into existence (see table). The largest purchases have been 28.75 million doses of the old-fashioned anthrax vaccine and 20 million doses of a new smallpox vaccine that's safe for people who have compromised immune systems. Beyond that, every acquisition is for a postexposure treatment instead of a preventative, and the number of doses—which is set by the Department of Homeland Security through a process known as material threat assessment—can protect against only limited attacks. There are fewer than 6 million doses of a treatment for exposure to radiation, and only enough botulinum antitoxin to treat about 100,000 people. Novel anthrax treatments, which theoretically would supplement existing antibiotics, total 75,000. A smallpox antiviral would treat 1.7 million. Several of these products have yet to receive FDA approval, and all have expiration dates; as a result, the U.S. government is the only market and will have to pay top dollar to keep fresh supplies in stock.

    Solid boost.

    A novel vaccine in the stockpile protects the immunocompromised from smallpox.

    CREDIT: HOW HWEE YOUNG/EPA/NEWSCOM

    Two reports last year evaluated the U.S. government's overall efforts to protect against a bioattack, and their conclusions were bleak. Although the reports focus on far more than BioShield, the project did not fare well. The congressionally mandated, bipartisan Commission on the Prevention of Weapons of Mass Destruction Proliferation and Terrorism issued a report card in January 2010 that gave the government an “F” for its efforts to “enhance the nation's capabilities for rapid response to prevent biological attacks from inflicting mass casualties.” It warned that both the White House and Congress had repeatedly tried to “raid” Project BioShield funds “for programs not associated with National Security.” (Congress transferred $137 million to combat pandemic flu and another $304 million to NIAID in part to support basic research for emerging infectious diseases.)

    The second report came from the National Biodefense Science Board, which guides HHS on scientific and technical matters related to chemical, biological, radiological, and nuclear weapons. The board's March 2010 report, Where Are the Countermeasures?, called the entire federal program “a good effort conducted by talented people.” But it criticized HHS for having “not fully tapped the talent” of DOD and said the program lacks strong centralized leadership and coordination. It further complained that there's no unified national strategy to focus on top threats and best responses. “America expects orchestration within HHS's scientific endeavors, not cacophony,” the report jabbed. “If achieving national [medical countermeasure] goals is likened to climbing a mountain, then most of the mountain remains to be climbed.”

    Robinson contends that many people have held Project BioShield to unfair standards, noting that it developed nine products in 7 years. “A company would be unbelievably successful if it were able to do this,” he says. What's more, he says, companies regularly have hiccups or failures, but in Project BioShield, “we're expected to have none.”

    Robinson says the country is safer now. “We have things that were not available in the United States 7 or 8 years ago. That's a pretty good measure of success. If we had any of those [bioterror] events, we would be using those products.” And he says BARDA has developed a much more diversified portfolio that will fill the SNS with a wide array of new medicines. “We're on the right course,” he assures.

    As Project BioShield has evolved, it has developed a broader target that's more attractive to industry. “We're moving away from one-drug, one-bug solutions,” NIAID's Kurilla says. Robinson notes that BARDA awarded several contracts for drugs to combat strains of anthrax, tularemia, and plague that have developed resistance to existing antibiotics. These same antibiotics have applications beyond biodefense: They can be used to treat people who have acquired multidrug-resistant infections. “Large pharma basically had shut their projects on these antibiotics because they didn't see the markets,” Robinson says. Now that Project BioShield has offered what looks like a more sustainable market, he says, big pharma “has picked up on that.” In the past 2 years, BARDA has also funded new efforts to make a recombinant anthrax vaccine and novel treatments for skin and lung problems caused by chemical or radiation attacks.

    BioShield, take 3

    The centerpiece of the next incarnation of BARDA and Project BioShield is the result of yet another review by HHS of its medical countermeasures for bioterrorism and emerging infections—and again highlights tensions with DOD. The review, conducted by all involved HHS divisions, concluded that HHS should establish Centers of Innovation for Advanced Development and Manufacturing, which would essentially be manufacturing plants to help small companies produce commercial quantities of drugs and vaccines.

    HHS initially hoped BARDA would work with DOD to build these plants, but the two agencies now plan to contract out their own facilities. “DOD and HHS started together but decided for reasons beyond me to go separately,” Kadlec says. “I have no confidence that we're looking for benefits and cost savings and leveraging expertise and scarce resources.” Robinson said DOD's unique mission to protect soldiers with vaccines against potential bioweapons ultimately led the department to go its own way; none of what it manufactures will go into the SNS.

    So far, only HHS has issued a solicitation to build the new centers, which could manufacture anything from chemical, biological, radiological, and nuclear countermeasures to pandemic flu vaccines. Robinson says he expects HHS to issue contracts early next year and that construction should take 18 months to 3 years. “You can't do it any faster,” he says. “Concrete doesn't set very well when you start putting stuff on top of it too soon.”

    Ultimately, Project BioShield's fate depends on funding. The initial legislation expires in 2013, and a bill now in the House of Representatives would keep the effort alive until 2019, adding $2.8 billion to its coffers. “It's going to be more successful as we go forward because we've made the course corrections midstream to put the dollars where they are needed,” Robinson says.

    Project BioShield's future success will also likely depend on its ability to balance natural versus intentional threats and better define how it can work with DOD to protect the country if the unthinkable happens.“The real problem,” the University of Michigan's Baker says, “is that none of these agencies seem to play well with each other.”

  7. Biodefense: 10 Years After

    Helping Hollywood Create and Battle a Pandemic

    1. Jon Cohen

    The writer and director of the upcoming film Contagion tapped Ian Lipkin of Columbia University to keep the reels real.

    The trailer for the new movie Contagion shows these words surrounded by viruses floating forward: NO ONE IS IMMUNE … TO FEAR.

    The “deadly disease assaults the planet” genre has a long, ludicrous history, with the offending pathogen arriving from outer space (Andromeda Strain) or a medical treatment gone awry (I Am Legend) and scientists deriving cures from laughably implausible sources such as a mystery serum mixed with monkey antibodies (Outbreak). Contagion, directed by Steven Soderbergh (Traffic; sex, lies, and videotape; Ocean's Eleven) and written by Scott Burns (The Bourne Ultimatum), makes an unusual attempt to avoid groans from the scientific cognoscenti. “They really are obsessed with trying to be accurate,” says Ian Lipkin, a neurologist–molecular biologist at Columbia University who specializes in disease outbreaks and was hired as a script consultant for the movie.

    Lipkin, an M.D. who also directs the Northeast Biodefense Center, worked with science writer Laurie Garrett to help Soderbergh and Burns go from concept to the final editing room. The plot blends lessons from several recent events—including bioterrorist attacks, the SARS outbreak, and the 2009 H1N1 flu pandemic—in an attempt to realistically depict transmission of a deadly new agent and the public health response from the likes of the U.S. Centers for Disease Control and Prevention (CDC), the U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID), and politicians. Contagion opens 9 September, 2 days before the 9/11 anniversary.

    Q:Gwyneth Paltrow. Matt Damon. Kate Winslet. Jude Law. Ian Lipkin? How does that happen?

    I.L.:The keys here are Scott Burns and Steven Soderbergh. My understanding is they were making another movie, The Informant!, and somebody sneezed. They began to riff on the idea of someone becoming sick and it moving from one person to the next. Scott contacted me and Laurie Garrett, and we met with him in New York maybe 3 years ago now and started talking about various ways a pandemic might initiate and spread. We threw out several ideas, and every one had to meet a sort of smell test of whether it was real.

    This was about the time the first cases of human-to-human transmission of Nipah virus were described. Nipah is a paramyxovirus and a relative of Hendra virus, and the first major outbreak, in Malaysia, was a result of bats infecting pigs and then pigs infecting farmers. I said, “Wow, this would make sense.”

    This particular virus doesn't just cause respiratory disease. It gets into the brain and results in seizures and coma and death, which made it much more exciting and interesting, because there's a lot more you can do with it than just watching people gasping for breath. Steven and Scott really liked this.

    No nonsense.

    Ian Lipkin (top) says he made sure the words and actions of the all-star cast in Contagion (bottom) were scientifically accurate.

    CREDITS (TOP TO BOTTOM): CLAUDETTE BARIUS; © WARNER BROS.

    Q:What is the virus the movie uses to wreak havoc on the world?

    I.L.:We designed the virus. We took sequences of Hendra and Nipah viruses and stitched them together and created a cross-over event to make [an imaginary] chimera. We did phylogenetic trees based on real sequences, pulled some old Nature papers describing the ephrin receptor for Nipah and Hendra, which is present in CNS [central nervous system] and the lung. We recolored it as a stick model and made it a 3D figure that rotates.

    Q:Why did you bother inventing a virus that doesn't really exist?

    I.L.:I wanted to come up with a plausible explanation for why this thing became so much more pathogenic and capable of transmitting to humans.

    Q:What sort of input did you have as the project developed?

    I.L.:I spent 20 days on the set. I approved all the props, costumes, and name tags. They have bona fide equipment. I took them to CDC twice. I took them to USAMRIID. I got them into a BSL-4 [the highest biosafety level laboratory].

    I had actors train in the lab. Jennifer Ehle and Kate Winslet learned how to pipette and run an agarose gel, and Elliott Gould moved things in and out of liquid nitrogen. He was going into a liquid nitrogen tank without a glove. I said, “You can't do that Elliott! You'll kill yourself.” We had to educate these guys.

    Steven said if it's not real, we have to reshoot it. He's a real stickler. This is not going to be I Am Legend or Outbreak. This is good science.

    Q:Do you do a cameo?

    I.L.:I do. I stand right behind Demetri Martin when the ability to grow virus for the first time is shown.

    Q:There have been a lot of these types of movies. Why do we need another?

    I.L.:This is very different: It's a Soderbergh movie, like Traffic. Scenes weave together. You see the effects of civil unrest mixing with the difficulties of vaccine production. We talk about scarcity: There's a lottery to distribute the vaccine, and we show how people want to protect their families at the expense of others. People learn the principles of transmissibility and about how viruses can become more virulent. There's social distancing. We have people blogging about pseudocures, which is what happened during SARS.

    When you look at this, you know, it's a movie, and it's got to sell tickets. But there isn't going to be anything in here that anybody can say, “My God, that's garbage.”

  8. News

    The Life Hacker

    1. John Bohannon

    He is a pioneer of genome sequencing, but Harvard University's George Church wants to do more than read DNA. He is changing the genetic code itself

    CREDIT: MARIE WU

    BOSTON—“We're going into the inner sanctum,” says George Church, gliding through a series of doors and passages, waving his key card to get in. At the center of this labyrinth in Harvard University's Wyss Institute for Biologically Inspired Engineering is a tiny locked room that Church opens with an old-fashioned metal key. Inside is a device that the 57-year-old biologist invented and built with the help of a local robotics company. He calls it MAGE, and it does look slightly magical, as if the contents of a molecular biology laboratory have flown off the benches and arranged themselves into a box. The effect is enhanced as Church—nearly 2 meters tall with an impressive wizard's beard—looms over the desk-sized contraption. But the real magic comes with what MAGE does: Millions of normal Escherichia coli bacteria go in one end; a vast menagerie of microbes with new genomes comes out the other end. “I'm hoping this thing will be worth $200 billion,” he says.

    A statement like that isn't unusual for Church. It sounds brash at first, but laboratories around the world are trying to genetically alter bacteria and other kinds of cells to make industrial chemicals from biomass efficiently, and the potential payoff is huge. Church argues that MAGE, which stands for multiplex automated genome engineering, will be an indispensable tool for doing that.

    In a debut of the technology several years ago, Church produced billions of different versions of the E. coli genome, identifying one that is five times more efficient at producing the antioxidant lycopene (Science, 21 August 2009, p. 928). “That was just a proof of concept,” he says. Now he's setting his sights on more lucrative chemicals, such as dyes, and also on enabling MAGE to refashion nonbacterial genomes.

    Synthetic biology, with its goal of reengineering cells as industrial machines, is the epitome of ambition. But even in a field of risk-takers, Church stands out. “He always talks about such wild experiments,” says J. Christopher Anderson, a synthetic biologist at the University of California, Berkeley, and one of Church's collaborators. “And then he rolls them out. He actually makes some of them work.”

    Church's scientific risk-taking has paid off. Earlier this year, Church was elected to the U.S. National Academy of Sciences. He is one of four scientists sharing a $20 million grant from the U.S. National Institutes of Health to develop efficient ways to change the genetic makeup of stem cells as a way of treating disease. Church has also helped to create or guide more than two dozen start-up companies and generated 34 biotechnology patents himself—not to mention leading the charge in personal medicine with his Personal Genome Project, in which he and others voluntarily bared their genomes (Science, 21 December 2007, p. 1843).

    “There are people who are good at identifying the problems for the field, and there are others who are good at doing the experiments,” says Jason Chin, a molecular biologist at the University of Cambridge, U.K. Church is rare in that “he does both.”

    But whether Church can pull off his most ambitious experiment—reinventing the genetic code—is another question. If he succeeds, biotechnology will have a new workhorse cell. And the planet will have a novel life form.

    Flunking and thriving

    The faint twang in Church's accent betrays his roots in Florida, where he grew up with a series of father figures before heading off to boarding school at 13. He showed a precocious talent for hacking complex systems—not just figuring out how the systems work but subverting them to his will. At the age of 10, he built an analog calculator from spare radio parts. By 16, he was writing his own computer programs—he tried everything from ecological modeling to algorithmic poetry.

    By the time he became a graduate student in the 1970s, Church was already an accomplished scientist, with a high-profile paper modeling how proteins bind to DNA. He also wrote the software that helped solve the structure of transfer RNA (tRNA), a molecule that helps make proteins and would later become central to his grand quest.

    Yet in 1976, 2 years into his Ph.D. studies at Duke University, Church ran into trouble. He had skipped so many classes to spend more time in the lab that he was about to flunk out. Fortunately, Harvard accepted the distracted student, who buckled down and took the required classes. “I'm glad they took a chance on me,” says Church, now a Harvard professor.

    When Church finished his Ph.D. in 1984, it seemed impossible to read the sequence of a cell's genome, let alone tinker with its content. Church and his Harvard Ph.D. adviser, Walter Gilbert, invented one of the first automatic DNA sequencing methods, widely popular at first but then overtaken by another technology. Just a few years later, Church invented multiplex DNA sequencing, in which many DNA strands can be deciphered in parallel (Science, 8 April 1988, p. 185), a method that has inspired countless applications, such as computer chip–like microarrays that track the activity of thousands of genes.

    Church took a cue from telecommunications. Thousands of simultaneous telephone conversations can share the same wire because the data streams are uniquely tagged and then combined—“multiplexed”—so they can be teased apart at the other end. Similarly, with fluorescently glowing molecules as tags, and the help of computers to make sense of the data, Church showed that the chemistry of millions of separate molecules, such as strands of DNA, could be tracked and analyzed.

    Church's latest ambition is not just to sequence genomes but to completely redesign them. The M in MAGE, the contraption locked away in his lab, is what makes this possible. By multiplexing many simultaneous changes to DNA within a single population of cells, rather than the traditional method of sequentially introducing changes in one generation of cells at a time, Church can edit genomes on the fly, creating a vast diversity of bacteria to evaluate for their commercial utility.

    The ultimate hack

    Church has even more ambitious plans for MAGE. He wants to hack into a cell's genetic code to make the cell impervious to viruses. That could be a boon to industries that use giant batches of bacteria and other cells to churn out enzymes and other valuable chemicals, Church notes. He points out that in 2009 a virus contaminated drug-producing hamster cells at the nearby biotech company Genzyme. The virus shut down a whole plant, leaving patients stranded.

    The complicated, multistep hack that Church believes can make cells virus-proof revolves around the way genes encode their protein-making instructions. Genes are inscribed as a series of DNA base-pair triplets, called codons. The triplet combinations of DNA's four-letter alphabet give rise to 64 possible codons, more than enough for the cell's 20 amino acids, as well as stop signals to mark the ends of genes. To make a protein, specific tRNA molecules read these codons and, until a stop codon is reached, attach the right amino acid to a growing chain.

    Viruses take advantage of this system by using the very same codon code in their genes and thus fooling the cell's tRNAs into helping to churn out viruses. But what if Church changed the cell's genetic code and the way tRNA handled that code? With the cell thus rewired, any infecting virus trying to replicate would only make gobbledygook proteins.

    The crucial first step is to “free up” a codon in a cell's genome. Because there are multiple codons that specify the same amino acids, one type of codon can be swapped for another that does the same job. If one did this across the entire genome, making a synonymous swap for every single instance of a codon, then the cell no longer needs that codon's tRNA. So there would be no harm done by deleting it. But viruses still depend on the codon, and when they infect this modified cell, that lack of that tRNA would cause viral protein production to hit a premature dead end (see diagram).

    Virus immunity.

    After one of the transfer RNAs is edited out from a cell's genetic code, invading viruses (red) should get nowhere.

    CREDIT: K. ENGMAN/SCIENCE

    All that swapping and deleting is easier said than done, however. “We thought about doing this back in 2003,” Anderson says. “But we realized that with traditional methods, it would take forever” because thousands of changes to the genome were required. In addition, such wholesale genome editing might cripple the cell.

    In July, a team led by Church showed that cells can handle at least some genome editing. The researchers freed up one of the three stop codons in E. coli (Science, 15 July, p. 348). In each of the 314 places in the E. coli genome where the “amber” stop codon marks the end of a gene, they used MAGE to replace it with an “ochre” codon, which does the same job. And in unpublished follow-up work, they deleted the gene for the protein that reads the amber codon. These strange new bacteria are alive and well, Church says.

    Getting from here to virus resistance will require much more work. Instead of eliminating a stop codon in cells, Church's team has to make at least 3000 replacements to get rid of an amino acid codon, not to mention deleting the gene for the corresponding tRNA.

    Whether a cell can survive this massive rewiring remains to be seen. But if the virus-resistance hack works, it may be possible to further modify the cell's code such that its genes cannot be read correctly by other cells should the genes escape into the environment, making Church's new life forms environmentally friendly.

    There are other efforts under way to hack the genetic code and teach cells new tricks. Like the DNA sequencing method he helped create 20 years ago, Church's rewired cells may turn out to be an alsoran. “Synthetic biology is such a young field,” Chin says. “It's not clear what research will stand the test of time.”

    Church isn't worried. He continues to tinker with MAGE, trying to make a version that will allow him to edit the genomes of stem cells to treat cancer and other diseases. But his dreams don't stop there.

    “I wouldn't mind being virus-free,” he says with equal parts mirth and earnestness. It may be too late to reengineer all of his own cells to prevent viral infections, but Church doesn't rule out the possibility of rewiring the genome of a human embryo to be virus-proof. That would be the ultimate life hack.

  9. News

    Algae's Second Try

    1. Robert F. Service

    Fifteen years ago, the United States gave up on algae-based biofuels. Now synthetic biology has helped revitalize the field.

    In Science, as in baseball and comedy, timing can be everything. John Sheehan learned that the hard way when he strove to make biofuels from algae from the late 1970s through the mid-1990s. The effort at the National Renewable Energy Laboratory (NREL) in Golden, Colorado, surveyed more than 3000 algal strains for their ability to produce oils that could be converted into diesel and other transportation fuels, then looked for ways to boost oil production in the best ones.

    It wasn't enough. Faced with a tight budget, the U.S. Department of Energy (DOE) killed the program in 1996, opting instead to focus its limited funds on turning agricultural wastes and other “cellulosic” material into ethanol.

    Fifteen years later, the algae biofuels business is thriving. Since 2000, more than $2 billion in private funds have flooded into the field. In May, Solazyme, an algae biofuels company in South San Francisco, California, raised $227 million on the stock market. Last year, ExxonMobil announced it would invest up to $600 million in the field, with up to half going to Synthetic Genomics, a San Diego, California, startup looking, like Solazyme, to use synthetic biology to create commercial fuelmaking algal strains. And DOE and other U.S. federal agencies have jumped back on board contributing hundreds of millions of dollars more, including $104 million from the recent economic stimulus package to Sapphire Energy in San Diego to build a large-scale algae fuel demonstration facility in New Mexico. Even Sheehan is back in the biofuels game again, studying the environmental impact of bio-based fuels at his new home at the University of Minnesota, Twin Cities.

    New crude?

    Synthetic biology helps researchers make high-oil-producing algal strains.

    CREDIT: COURTESY OF SAPPHIRE ENERGY

    So why the change? In short, better timing, Sheehan says. Biotechnology has made massive strides in recent decades, now making it relatively easy to tinker with algae in ways not possible during the first flurry of interest. “The tools we had to use to manipulate algae were medieval compared to what we have today. Synthetic biology didn't exist in 1996,” Sheehan says. As a result, despite algae's advantages, he and others could not overcome the high costs of obtaining oil from these organisms.

    But now, companies are using synthetic biology techniques, along with other biotech and engineering advances, to bring those costs down, making algae more efficient by changing the way the organisms use light, increasing the oil content of cells, and improving their efficiency at producing fuel precursors. A spate of recent advances “gives me more assurance that this isn't just folly,” Sheehan adds.

    It's easy to see why plenty of scientists and investors agree with Sheehan. For starters, with fossil fuels becoming increasingly scarce, expensive, and a source of political instability, the potential market for replacing these liquid transportation fuels is worth trillions of dollars per year. Corn- and sugar-based ethanol production already has a share of that. But because a liter of ethanol has only two-thirds of the energy content as the same volume of gasoline, the alcohol isn't well suited for fueling aircraft and heavy trucks, big chunks of the transportation industry. Plants that produce more energy-rich oils for biodiesel, such as soybean and oil palm, are a better fit in those areas. But these plants produce at most 5930 liters of fuel per hectare per year, according to DOE's 2010 National Algal Biofuels Technology Roadmap.

    Fast-growing algae, on the other hand, can produce between 9353 and 60,787 liters per hectare per year of fuel. And some algae companies are convinced that they will ultimately do much better than that. If such a promise comes to pass, algae farms on the scale of Colorado could produce all the gasoline used in the United States each year, a small fraction of the land that would be required for making a comparable amount of biofuels from corn or cellulose (see figure).

    Furthermore, unlike most plants, some strains of algae thrive in brackish water, salt-water, or even waste treatment water. Algae farms can also be sited on land unsuited for traditional agriculture. So, in theory, large-scale algal fuel production would not interfere with food production the way other biofuels can. “The fundamental biology makes algae a massive opportunity for humanity,” says B. Greg Mitchell, an algae researcher at the University of California, San Diego (UCSD).

    But as Sheehan and his NREL colleagues learned early on, algae-based fuels present many challenges, ones that still make them prohibitively expensive. Despite the fact that algae grow quickly, they typically make up only 0.1% of the volume of the water in which they grow. That means collecting a kilogram of algae requires processing 1000 kilograms or more of water, an energy-intensive operation. The algae must be harvested and their oil extracted, collected, and processed into the final fuel. Those challenges currently make the cheapest algal fuels cost about $2.25 per liter, more than double today's average gasoline price in the United States, NREL researchers say.

    Competitive advantage.

    Fast-growing algae yield more fuel per hectare than other biofuel producers.

    MAP: ADAPTED FROM G. CHARLES DISMUKES ET AL., CURRENT OPINION IN BIOTECHNOLOGY, 19 (2008);

    Green design

    How individual companies are trying to cut costs depends in part on the type of alga they use and how it's grown. The most popular strategy to grow algae is in sunny, open-air, shallow ponds. But because the algae shade each other, they grow at a low concentration and thus a large amount of energy must be spent concentrating them and harvesting the oils they produce. Competition from other algae strains that blow in and bacterial and viral infections further compromise the efficiency of open ponds.

    A separate approach grows the organisms in closed chambers called bioreactors. These chambers can be either transparent, to allow the algae to grow using sunlight, or opaque, in which case the algae are fed sugars or other nutrients to promote their growth. Although bioreactors can grow algae at a greater density, they cost much more than open ponds to set up and operate.

    Synthetic biology is helping researchers produce fuels more efficiently in both settings. “We can very quickly do lots of genetic manipulations with synthetic biology,” says Alex Aravanis, chief technology officer of Sapphire Energy. “We can go orders of magnitude faster to discover key genes related to yield.” A few years ago, the yield had been stuck, with no more than 40% of the alga's weight being oil. Now, with synthetic biology's ability to alter algal metabolic pathways en masse, rather than one gene at a time, “we have the opportunity to drive those efficiencies to unprecedented levels,” says Stephen Mayfield, an algae biologist at UCSD.

    Some synthetic biology efforts have gone into making indirect improvements in oil yield. Richard Sayre, a molecular biologist at the Donald Danforth Plant Science Center in St. Louis, Missouri, and his colleagues are improving algae's biofuels potential by engineering them to absorb less light, thereby leaving more energy available to nearby algae.

    Under natural conditions, individual algae hog the light in an effort to outcompete their neighbors: Their light-absorbing molecular complexes, called antennas, really use just one-quarter of the photon energy they absorb. So Sayre and his colleagues inserted a new set of metabolic instructions to make the algae more community-oriented. They directed the single-celled plants to adjust the size of the antennas such that in bright light, they absorb only enough photons to make as much oil as possible, leaving the rest for neighboring cells. Preliminary studies, presented in August at the American Society of Plant Biologists (ASPB) conference in Minneapolis, Minnesota, show that the strategy increased the population's growth rate by 30%.

    Test bed.

    Open-air “raceway” ponds grow algae cheaply but must contend with infections and predators.

    PHOTO: COURTESY OF SAPPHIRE ENERGY

    That's not the only algae makeover under way. Sayre's team is also boosting metabolism in algae by giving them a human gene for an enzyme called carbonic anhydrase (CA) II, which helps regulate carbon dioxide in red blood cells. In the algae, it converts an inorganic form of cellular carbon into carbon dioxide, which can then be used in photosynthesis to ultimately make oils. The human CA is far more efficient than the algae's own CA. With it, algal photo synthesis rates jumped between 30% and 136% depending on the test conditions, the team also reported at the ASPB meeting.

    Gushing with oil

    Numerous companies are pushing the limits of algal biology in other, poorly disclosed ways. Harrison Dillon, president and chief technology officer of Solazyme, will only say that his company has engineered algal strains with an oil content of over 80% of their weight. Those strains are grown in bioreactors and fed sugars. Last year, Solazyme produced 416,395 liters of oil and announced that it can produce algae-based fuel for less than $120 a barrel, only slightly more than the recent cost of petroleum.

    Sapphire's Aravanis adds that his company is using synthetic biology to come up with and rapidly survey thousands of different genetic manipulations of photosynthetic algae in an effort to make high-oil producers. As part of that program, it has identified several genes, some from algae and some from other organisms, that when inserted into lipid biosynthesis pathways increase oil production enough that if scaled up, the algae could produce an additional 4675 to 9383 liters per hectare per year. These results have yet to be realized in field trials, but the company is currently building a demonstration facility in New Mexico that is expected to produce between 5000 and 10,000 barrels of oil per day by 2018.

    Focusing on a different organism, researchers at Joule Unlimited in Cambridge, Massachusetts, meanwhile, are improving the efficiency of photosynthetic bacteria for producing hydrocarbons to make diesel. These bacteria secrete hydrocarbons, so Joule researchers are modifying the bacteria to grow more slowly and instead to divert carbon dioxide almost exclusively into making hydrocarbon fuels. According to Dan Robertson, Joule's head of biosciences, the company now has strains that routinely convert 90% of the carbon atoms that come in as carbon dioxide into fuel molecules secreted by the organisms. The company is currently operating a pilot plant in Leander, Texas, and plans to open a large-scale demonstration plant in New Mexico next year.

    With these and other innovations now taking hold, Sayre is hopeful: “I'm convinced this time around we're much smarter and have a better shot at succeeding.”

  10. News

    A Lab of Their Own

    1. Sam Kean

    Do-it-yourself biologists in New York are following their dreams, setting up a community lab that combines synthetic biology with art, fun, and perhaps profit.

    A squeeze.

    A dozen GenSpace members, including (left to right) Sung won Lim, Russell Durrett, and Ellen Jorgensen, share two tiny labs.

    CREDIT: DAN GRUSHKIN

    NEW YORK—It's 4 p.m. on a summery Wednesday afternoon, and four members of GenSpace—two former biotech scientists, an undergrad on hiatus from school, and a person who runs next-generation DNA sequencers at a local medical school—are sitting around on mismatched chairs on the seventh floor of this former Flatbush bank, sipping Magic Hat beer and reflecting on the oddity of becoming minor scientific celebrities. GQ France did a photo spread recently on the writers, artists, and biologists who practice biology at GenSpace, and the Guggenheim Museum approached them about collaborating on an exhibit to teach synthetic biology. Low-brow TV producers even pitched the idea of a reality show based at this “community lab,” a place where professionals and amateurs alike tinker with life forms and engineer DNA. GenSpace turned the producers down, and things soured with the Guggenheim, but amid any disappointment, members marvel at the continued, and sometimes lurid, fascination they've dredged up. “I've been really surprised at all the attention,” says president Ellen Jorgensen.

    Eventually, talk turns back to biology, and other GenSpace members start drifting in. Indeed, says GenSpace vice president Daniel Grushkin, a science writer, “GenSpace is like a gym membership” in that people come and go 24 hours a day. Grushkin spends the afternoon sketching out plans to use a bacterium to genetically transform the worm Caenorhabditis elegans and make it fluoresce. “It's a few steps above a pet rock,” he suggests. And amid these discussions of organisms and experiments, all the other distractions fall away. That's why this crew had founded GenSpace, after all—to do their own biology, on their own agenda.

    With the lab's debut in December 2010, GenSpace opened a new chapter for the do-it-yourself (DIY) biology movement, which some say parallels the garage computer culture in the 1970s that helped usher in the personal computing revolution. (Some DIY biologists even call themselves “biohackers.”) But although the New York crew was the first to commit to a formal lab space for community biology, they're not alone. BioCurious, a DIY biology team near San Francisco, California, founded in 2009, has recently signed a lease for a 220-square-meter office in the Bay Area that will be turned into lab space.

    Whether many more GenSpaces will arise is tough to predict. It's hard to quantify the number of active DIY synthetic biologists. Thousands of people trade tips (and jabs) in online forums, and the Web site DIYbio.org has seen its membership grow by orders of magnitude since starting in April 2008. But the number of people doing “wetwork” is significantly smaller, acknowledges Jason Bobe, who co-founded DIYbio.org.

    Although not a biologist herself, Bio-Curious co-founder Eri Gentry says she hunted down lab space to rent because biology students she knew through BioCurious had grown weary of pursuing narrow Ph.D. research topics and wanted to tackle side projects they were passionate about. The setup in most science labs today “doesn't breed creativity,” she argues.

    That's a common sentiment in DIY bio, and it motivates much of the passion. Scientists are born tinkerers, says Jorgensen, also an assistant professor of pathology at New York Medical College. “This place is made for spare-time tinkering.”

    Indeed, as James Collins, a synthetic biology pioneer at Boston University, points out, “when we started synthetic biology, most of us were amateurs. We came from engineering, physics, computer science, and other fields.” Still, “amateurs” like Collins, although biology neophytes, worked at universities and had access to expensive research equipment. Almost by definition, DIY biologists lack that access, and Collins argues that they will thus have a tough time making significant contributions.

    Building communities

    GenSpace started in 2009 after several like-minded New Yorkers met online through the Google group DIYbio. For months they puttered around with experiments in Grushkin's living room, but late last year they graduated to their new space: two boxcar-sized labs, each about 10 square meters, and a lounge on the top floor of a building that is primarily an artists' collective. The move to a permanent place was important for doing better science, Jorgensen says: “We kept hitting obstacles easily solved with the creation of a community lab. Suppliers of reagents often won't ship to residential addresses, and you need a separate fridge for storage so [microbes] won't contaminate food.”

    Like a clubhouse, the labs are cobbled together, in part from the impressive piles of junk lying around the building. “A lot of sweat equity went into this place,” says Oliver Medvedik, who earned a Ph.D. from Harvard University in biomedical science and has taught there in the past few years but focuses on being GenSpace's director of scientific development. Many of GenSpace's lab benches are countertops salvaged from restaurants. Centrifuges, a PCR machine, and other equipment were donated by Jorgensen's previous employer, a biotech company that laid her off and had to unload things as it downsized. Medvedik even scouted eBay, finding an incubator that he ultimately bought off a truck in Jersey City, New Jersey, for $659.

    The research equipment is integral to Medvedik's plans to genetically engineer bacteria to turn colors (perhaps from blue to yellow) in the presence of arsenic, to test groundwater in places like Bangladesh.

    Citizen science.

    The classes for the public that GenSpace teaches have brought in most of the lab's revenue so far.

    CREDIT: DAN GRUSHKIN

    Even with a dedicated lab, though, the work Medvedik and others are doing is not easy. All DIY biologists have access to the international Registry of Standard Biological Parts, snippets of genetic code that can be popped into cells and microorganisms, much as resistors or capacitors can be popped into electrical circuits, and that should produce certain molecules or effects each time. But at a “synbio” meeting in July 2010, participants reported that of the registry's 13,413 parts listed then, 11,084 didn't work. As one presenter noted, “Lots of parts are junk.” Wary of this, Medvedik and others say they must carefully test each registry part before relying on it.

    GenSpace members also pay close mind to biosafety. Medvedik or Jorgensen gives all new recruits a 90-minute safety briefing and lab tour, similar, Jorgensen says, to what typical graduate students get. GenSpace has government and university safety officers on its advisory board, and it stays in contact with FBI agents as well. It even invited agents to one of its “strawberry mayhem” events, at which participants (usually children) mash fruit and extract DNA. The group also screens new members' projects carefully, having recently rejected a proposal involving human pathogens that cause acne.

    Besides accepting donations and scrounging for hardware, GenSpace helps make ends meet by offering biology classes to the public. The 12 GenSpace members pay just $100 per month for lab access, but the group charges $300 per student for a 4-week course that includes learning lab techniques such as gel electrophoresis and splicing DNA with restriction enzymes. Jorgensen and Medvedik have taught more than 60 students since January, with more classes planned.

    Students range in age from their 20s to their 60s, and most have no real science background. Alumni include a winemaker, biotech investors, and New Yorkers curious about personal genomics. In one class, Medvedik had students engineer Escherichia coli to produce pungent banana oil. “Some people want to do real MacGyver stuff ” like the TV secret agent, Jorgensen says, whereas others “are fascinated just by running a gel.”

    Different strokes

    Likewise, GenSpace members have different motivations for pursuing DIY biology. One of Medvedik's projects involves cultivating a fungus that can digest wood chips or sawdust. It converts those loose materials into a Styrofoam-like matrix, which could find use as an ecofriendly packing material or as insulation. Medvedik is also applying for Bill and Melinda Gates Foundation grants to expand his arsenic-detecting microbe project.

    GenSpace executive secretary Russell Durrett, who graduated with degrees in biochemistry and anthropology from New York University in May 2010 and now has a job running DNA sequencers at Weill-Cornell Medical College, joined GenSpace largely to develop ideas to spin off into a company or sell as inventions. Toward that end, GenSpace announced early on that its members would retain all intellectual property rights. Some biohackers were aghast at this, arguing that it runs counter to the open-source ethos of the computer culture that helped spawn DIY bio, and GenSpace was flamed online.

    But what makes sense financially in computing doesn't necessarily work in biotech, Durrett says, because organic parts take far longer to test and develop. His projects right now include designing fluorescent moss. He's also interested in producing cheap PCR machines: At a weekend-long “synbio binge” at GenSpace (an event inspired by “hack-athons” where amateur computer programmers gather and work together for days), he built a homemade PCR machine from plastic piping and a light bulb.

    Jan Mun, who took Medvedik's class in May after hearing about it on a digital media listserve, recently joined GenSpace for the sake of her art. She had been culturing mushrooms at her home for an environmental sculpture, but they died; most homes are not antiseptic enough for finicky 'shrooms. GenSpace was her solution, as she could grow them under sterile conditions. “It's very unusual to have access to a molecular biology lab,” Mun says, “and it's wonderful that they're open to artists.”

    Traditionally, there are certain scientific fields, such as high-energy physics, to which only professionals can significantly contribute. In other fields, such as astronomy or ornithology, committed amateurs can do important work.

    Synthetic biology is currently the first kind of science, but by teaching classes and opening community labs, groups such as GenSpace and BioCurious strive to make it the second: to welcome Mun's artistic mushrooms alongside Medvedik's humanitarian bacteria or Durrett's entrepreneurial mosses. It's ambitious for such small groups, but Jorgensen welcomes the eclectic mix. DIY bio, she says, “is called a movement because it's just that. It's not organized and means different things to different people.” Despite recruits like Mun and spreads in GQ, GenSpace isn't quite mainstream yet, but Jorgensen predicts it will be: “We feel the future is community labs.”

  11. News

    Visions of Synthetic Biology

    1. Sara Reardon

    Artists are embracing synthetic biology as a tool, but not necessarily as a promising way for the future.

    CREDITS (LEFT TO RIGHT): ALEXANDRA DAISY GINSBERG (3); JOE DAVIS ©PIETER BAERT

    Inside Vienna's Museum of Natural History, the Bio:Fiction film festival and its sister art show, Synth-ethic, abound with living fantasia. The world's first art exhibition specifically devoted to synthetic biology, its exhibits are a gamut of interpretations of the emerging field, ranging from the celebratory to the alarmist. One short film sings the praises of a synthetically engineered future complete with glowing trees, a cure for cancer, and a biologically grown spaceship. Another shows how synthetic biology could lead to the devaluing of life. In it, a gamer uploads a superhero's genetic code into a piece of meat through a USB cable, directs the resulting humanoid around with a videogame controller, and eventually suffocates him in a plastic baggie. The art show is similarly diverse, showcasing “Nanoputians”—organic chemicals whose molecular structures resemble human stick figures—a sparkling arrangement of tubes and glassware that recreates the Miller-Urey origin-of-life experiment, and slimy, semiliving “worry dolls”: cells on scaffolds to which visitors whisper their concerns about biotechnology.

    But it's no accident that the show takes place in a museum of natural history, not art. “They're not just evocative objects,” says Synth-ethic curator Jens Hauser. Nor are they simply educational illustrations of synthetic biology. “They're cynical design,” using synthetic biology to critique synthetic biology.

    As the field has grown during the past decade, so has interest in using its tools for nonscientific purposes. These are early, heady days for a field that promises to revolutionize medicine (see p. 1248), the chemical industry, and genetic engineering, to name just a few. A growing number of artists are attracted to it as a technique and also because of the interesting ethical questions it raises.

    Many of these artists work directly with research scientists. Their creations add a cultural counterbalance to the field's tendency to view life like circuitry, a utilitarian perspective that increasingly drives synthetic biology and, they say, informs the public's understanding of it. They find themselves uniquely placed to ask hard questions about the ethical and social issues raised by synthetic biology. While special interests that want to either promote or condemn the nascent science have been eager to fund artistic interpretations of it, they are finding they may not get the results they hoped for.

    Yet unlike engineers focused on solving a problem, “artists are the ones in a position to ask questions of ‘why?’ or ‘should we?’” says Richard Pell, an art professor at Carnegie Mellon University in Pittsburgh, Pennsylvania. Continuing in that role is critical, he adds, because synthetic biology “should be thought about much longer than it takes to say ‘Frankenfood’ or ‘cure for cancer.’”

    Artists in the lab

    With the advent of streamlined genetic and tissue engineering, interest in science-inspired “bioart” has exploded. Synthetic biology itself provides a “wet palette of possibilities” as both a technique and a topic, says Oron Catts, co-founder and director of the SymbioticA program at the University of Western Australia in Perth. SymbioticA has hosted more than 70 resident bioartists since 2000 and even offers a Master of Biological Arts degree. Synthetic Aesthetics, a collaboration between Stanford University and the University of Edinburgh, funds six pairs of scientists and artists to work together exploring one another's world. Programs such as these, as well as the emergent do-it-yourself biology movement (see p. 1240), allow artists to work alongside scientists in order to learn both the molecular techniques and the realities of the field.

    Joe Davis, an artist and researcher at the Massachusetts Institute of Technology and Harvard University who has been in the bioengineering business for decades, is a perfect example. In the 1980s, annoyed with what he called the “absurdist” attempts by Search for Extraterrestrial Intelligence efforts to talk with extraterrestrials through radio waves, he encrypted the Arecibo Institute's famous binary message in DNA code, cloned it into spore-producing bacteria, and proposed launching them into space. Although it remained Earth-bound, this “Microvenus” project was his early claim to fame. Nowadays, he works in the lab of Harvard synthetic biology maven George Church (see p. 1236), sitting in on lab meetings, brainstorming with scientists, and reinterpreting ideas. Supported by his own art grants, he sees himself as the quintessential tinkerer, similar to the technically competent backyard rocket builders and radio enthusiasts of the past century.

    A crystal radio was precisely what Davis displayed in the Synth-ethic art show—one built of bacteria that naturally create their own communication lines, or nanowires. Engineered with a modified gene from a sea sponge that builds its own skeleton from silicon in seawater, the silicon-producing bacteria grow to form an electrically conductive circuit and are hooked to an antenna and speakers. The “radio” still has a few kinks, he says; he hopes to get it working soon. He and others in Church's lab are now trying to clone the modified gene into silkworms to see if the caterpillars will spin glass cocoons as art pieces.

    Mixed media.

    Artists' reactions to synthetic biology, from left: Daisy Ginsberg imagines the medical implications of synthetic biology as organs coated in biological crystals and a diagnostic suitcase of colorful poo. Joe Davis powers a crystal radio using bacterial nanowires. Tuur van Balen builds a window trap for pigeons to catch them and turn them into soap dispensers. And Oron Catts grows cells into the shape of “worry dolls” ready to listen to concerns about biotechnology.

    CREDITS (LEFT TO RIGHT): ©PIETER BAERT; TISSUE CULTURE & ART PROJECT

    Davis wishes more artists were willing to spend extended time in labs—where they experience both the excitement and constraints of cutting-edge science. Too many bioartists, he says, are more interested in shocking people than seeing what science is really about.

    Yet bioengineers are not always welcoming of the input—and potential criticism—of artists. The International Genetically Engineered Machine competition (iGEM), an annual program in which undergraduates create useful life forms from standardized genetic components, is often touted as the future of synthetic biology. But in 2009, art infiltrated this bastion of utilitarianism when a team from Bangalore, India, entered Escherichia coli they had engineered to produce the smell of rain before a monsoon. “It was the angle I'd always hoped to find at iGEM,” Pell says. Not everyone agreed, however, leading to a minor debate among the judges about whether such an impractical creation belonged at iGEM. In the end, the team got a “Best Presentation” award, and several other art pieces have since been entered.

    Catts says that this kind of creativity and “irrational design” have been providing a much-valued counterweight to the stolid logic of the field's many engineers and computer scientists. “There's a nice amount of mutual respect when a field is still embryonic and territories haven't been carved out yet,” Pell says. But as synthetic biology matures and becomes a lucrative area for investors and entrepreneurs, he expects there will be growing pressure on artists to present particular perspectives on the field. He fears this sweet period of artists freely cooperating with scientists may be nearing its end.

    Shades of ethical gray

    Eager to avoid the mistakes made with the introduction of genetically modified organisms, which drew irreparable backlash from the public, the scientific world, particularly in Europe, hopes to enlist the aesthetic contributions of bioartists to their cause. Institutions such as the U.K. Royal Academy of Engineering, in discussions about how to engage the public, have called on artists to help illustrate synthetic biology in outreach programs. And it's common practice for European companies, including some biotech firms, to include artists in their public outreach budget—with, Catts says, unspoken PR expectations.

    So Catts has been hard at work fighting what he sees as a concerted and premeditated effort to co-opt artists into helping engineer public acceptance of synthetic biology. “I think they've got a misconception about the role of artists in society,” he says. “It's art's place not just to make sense of [science] but to critique it.”

    But insofar as artists are interpreters, informing a society that gets its science in sound bytes, their messages span the range. For each shock artist who makes dire predictions and illustrations of “spider-goats”—inspired by a scheme to put a spider gene into goats—there exists what Catts calls a “technofetishist” who revels in humans' ability to modify the world and themselves.

    Yet most of those who have talked to scientists and learned about synthetic biology inhabit a middle ground. “It's an ethical gray zone I like to explore in my work, and I like people to engage with,” says designer Tuur van Balen of the Royal College of Art in London.

    Humor also plays a role: One of Van Balen's projects, Pigeon d'Or, consists of a window trap with pigeons. He envisions them eating a gut bacterium that he would “engineer” to produce a biological soap that could pass through the pigeon gut intact, spreading sudsy excreta. The idea? Feeding the bacteria to pigeons could draft them as the ecosystem's windshield washers. This absurd flight of fancy should make people stop and think about how synthetic biology might turn ecology on its ear.

    The question of how synthetic biology will affect larger organisms and ecosystems intrigues Alexandra Daisy Ginsberg, one of the founders of Synthetic Aesthetics. “There's something not so threatening about microbes,” she says. So she decided to make “something visceral: What will synthetic biology actually look like?” she asks. One of her projects, Synthetic Kingdom, explores environmental health effects. For instance, future organisms designed to make telltale red crystals when exposed to carbon monoxide might inadvertently colonize human lungs. In smokers, this could produce an artistic result: red lungs.

    Another Ginsberg piece, E. chromi (see image), imagines a future in which we ingest synthetic bacteria that turn our feces different colors according to the diseases we have. The project is a response, Ginsberg says, to the personalized medicine that synthetic biology promises. This “suitcase of poo” has won numerous art awards and is now being displayed in the Museum of Modern Art in New York City. For Ginsberg, who says she's “frustrated by misinformed visions” of the future, getting people to think about the technology's day-to-day implications is the most important issue.

    Her fellow artists also want to be thought-provoking. “I'm not a science communicator,” Van Balen says. “I don't want people to see my work and learn what synthetic biology is; I hope their reaction would be to walk away and scratch their heads and be a bit puzzled.”

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