News this Week

Science  14 Jun 2013:
Vol. 340, Issue 6138, pp. 1270
  1. Around the World

    1 - Washington, D.C.
    Safety Agency Backpedals on Preemie Study
    2 - Beijing and Washington, D.C.
    Reducing HFCs Under Montreal Protocol
    3 - Stockholm
    New Home for Nobel Prize
    4 - Rome
    Rally to Defend Science

    Washington, D.C.

    Safety Agency Backpedals on Preemie Study

    Breath of life.

    Study examined oxygen given to premature infants.

    CREDIT: WIKIMEDIA/BRIAN HALL

    Under fire from researchers, the U.S. government agency responsible for protecting human research subjects has shelved a 7 March decision to sanction the leaders of a clinical trial involving premature infants for not fully disclosing its risks (Science, 19 April, p. 254). "We have put on hold all compliance actions," the U.S. Office for Human Research Protections (OHRP) announced in a 4 June letter to the University of Alabama, Birmingham, which led the trial. OHRP's move came a day before The New England Journal of Medicine published two pieces arguing the agency overreacted. OHRP says that it plans to hold a public meeting on the matter, with an eye toward clarifying risk disclosure rules. http://scim.ag/preemiestudy

    Beijing and Washington, D.C.

    Reducing HFCs Under Montreal Protocol

    Breaking a policy logjam, China and the United States agreed on 8 June to work for deep global cuts in the use of potent atmospheric warming chemicals called hydrofluorocarbons (HFCs). The 1989 Montreal Protocol to protect the ozone layer boosted the use of HFCs as coolants in appliances, because they do less damage than chlorofluorocarbons. As HFCs' role in warming became clear, nations squabbled over whether to use the protocol or a new climate agreement to reduce use; now, the two powers have agreed to pursue reductions under the protocol. The White House estimates that cuts could erase greenhouse emissions equivalent to 90 gigatons of CO2 by 2050, or nearly 2 years' worth of current global emissions.

    Stockholm

    New Home for Nobel Prize

    Sweden's biggest research foundations have secured 800 million kronor ($122 million) to build a new Nobel Center in Stockholm that will bring the Nobel Museum, the Nobel Foundation, and Nobel Prize ceremony under one roof. The museum and foundation now have separate addresses, and the prize is awarded at the Stockholm Concert Hall. Come 2018, however, all would be united in the new venue. An architect for the project will be chosen in a global competition that enters its final phase this week.

    The Nobel Foundation welcomed the 4 June announcement that the Knut and Alice Wallenberg Foundation and the Erling-Persson Family Foundation (run by the chairman of fashion retailer H&M) had raised the necessary funds. The center will "generate scientific activities of the highest international caliber," says Lars Heikensten, the Nobel Foundation's executive director.

    Rome

    Rally to Defend Science

    Rallying cry.

    Researchers protest misinformation about science at Rome's Spanish Steps.

    CREDIT: ITALIA UNITA PER LA CORRETTA INFORMAZIONE SCIENTIFICA

    A flash mob of 30 researchers calling themselves Italy United for Correct Scientific Information appeared on the Spanish Steps of Rome on 8 June to protest an attack against an animal facility at the University of Milan in April. It was part of a series of protests and conferences in 15 cities across Italy this month to protest what organizers say is an antiscientific attitude in Italy and widespread "misinformation" about science in the media.

    "We want to show that we do not live in an ivory tower," says Dario Padovan, a biologist at the University of Trieste. "We are not afraid to defend our research and understand the need of communicating it correctly." Press coverage of April's attack, or of the conviction of Italian researchers for their failure to warn about the risk of a deadly earthquake in L'Aquila, shows that Italian media tend to focus on the emotional side of a story and fail to delve into the scientific facts, says Federico Baglioni, one of the organizers of the 8 June event. http://scim.ag/Italyrally

  2. Newsmakers

    Three Q's

    Altshuler

    CREDIT: MARIA NEMCHUK, BROAD INSTITUTE

    Last week, more than 70 research, health care, and patient advocacy organizations announced a "global alliance" to help researchers securely share genome sequences and clinical information. David Altshuler of the Broad Institute in Cambridge, Massachusetts, is leading the planning. http://scim.ag/Altshuler

    Q:Why is this alliance needed?

    D.A.:We have to be in a position to compare genomes and clinical data if we want to learn and … help people, like give them accurate predictions or learn the biology of a disease. It's going to take millions of genomes. Even in a given disease there are often many different genes that can play a role, and there are many, many different diseases.

    Q:Will you essentially merge different databases?

    D.A.:That's not what this is about. We're inspired by the example of the World Wide Web and also the Human Genome Project. The idea is to focus on standards and shared principles and ethics that would make it possible for many people to build things that would be individually innovative and yet collectively could learn from each other.

    Q:Have any of the big biobank projects, such as Kaiser Permanente and Vanderbilt, declined to participate?

    D.A.:They've not turned us down. There are only so many organizations that have thus far been part of the discussion … whether or not those organizations choose to participate will be up to them.

    New Max Planck President

    Stratmann

    CREDIT: AXEL GRIESCH

    Martin Stratmann, 59, who studies interface chemistry, surface engineering, and corrosion, was elected the new president of the Max Planck Society, one of Germany's main research organizations, on 6 June. Elected to a 6-year term today at the society's annual meeting in Potsdam, Stratmann will replace current president, developmental biologist Peter Gruss, next June.

    Stratmann is one of the directors at the Max Planck Institute for Iron Research in Düsseldorf and has been a vice president of the society since 2008. The society, which had a budget last year of €1.5 billion, comprises 80 institutes and research facilities and employs more than 5000 scientists. http://scim.ag/Stratmann

  3. Random Sample

    By the Numbers

    $65 Amount added to the U.S. economy per $1 of the $12.3 billion federal investment in genomics-related research, according to Battelle Technology Partnership Practice and United for Medical Research Group.

    $35 per metric ton The "social" cost of carbon emissions—an estimate of climate change damages to health, property, and agriculture—up from $21 per metric ton, per a statement last week by the U.S. Office of Management and Budget. All federal agencies must use the new number in regulations.

    $244 billion Amount of global investments in renewable energy in 2012, increasingly by developing countries.

    Lack of Sleep Leads to Award-Winning Screenplay

    Rising star.

    Student filmmaker Barnett Brettler (third from left) received $50,000 for his screenplay, Waking Hours.

    CREDIT: CINDY ORD/GETTY IMAGES FOR TRIBECA FILM INSTITUTE

    In the dystopian world of Waking Hours, a screenplay by University of California, Los Angeles (UCLA), film student Barnett Brettler, a disease called fatal insomnia doesn't just rob victims of sleep until they die of exhaustion. It "takes away their façade" by revealing their true emotions, he says.

    In real life, fatal insomnia is rare, produced by misfolded brain proteins. But in Brettler's script the world is overrun by its zombielike victims. Elwin, a border patrol agent in the United Kingdom, is charged with keeping the diseased out—but faces a dilemma when his scientist girlfriend wants to leave to help treat victims on the mainland.

    The idea occurred to Brettler during a program sponsored by the Alfred P. Sloan Foundation, which pairs young filmmakers with scientists. He worked with UCLA microbiologist Imke Schröder, whose enthusiasm for the project, he says, was "contagious."

    Now, Brettler has a chance to turn his screenplay into a feature film. In April, he received the Sloan Student Grand Jury Prize, an annual $50,000 award to help produce a student screenplay with a science theme. According to Sloan Vice President of Programs Doron Weber, the foundation has spent $3.5 million over the past 15 years to encourage young filmmakers to "be more open to the idea that there's good raw material in science and technology."

    ScienceLIVE

    Join us on Thursday, 20 June, at 3 p.m. EDT for a live chat with experts on the use and misuse of science in summer blockbusters. http://scim.ag/science-live

  4. On the Trail of Ancient Killers

    1. Ann Gibbons

    Armed with new methods, researchers are interrogating the DNA of centuries-old pathogens extracted from the bones and teeth of victims.

    Age-old affliction.

    An attendant in medieval times washes a leper's sores.

    CREDIT: SPL/SCIENCE SOURCE

    Last August, Johannes Krause was performing a feat that no one would have dared attempt a few years ago: He was carrying out a genetic autopsy on 700-year-old human remains. Working with DNA extracted from the tooth of a young woman who died in the 1300s in a leper colony in Denmark, Krause was calculating how much of the jumble of genetic material from microbes, contaminants, and humans was from the pathogen that caused the woman's leprosy, Mycobacterium leprae. He hoped for about 1% to 2%. To his surprise, a whopping 40% of the DNA aligned with the modern M. leprae sequence. Just 9% was human. Impossible, thought Krause, a paleogeneticist at the University of Tübingen in Germany.

    He did the analysis again and got the same answer. "It was crazy," he says. "I never expected to find way more pathogen DNA than human DNA in a human bone. You'd never find that in a modern patient who has leprosy."

    Krause excitedly called his graduate student, biochemist Verena Schuenemann, who had extracted and prepared the bone powder from the tooth. They realized that they had hit a scientific jackpot. "With this high concentration of bacteria, we'd try to make a dream come true," Schuenemann says. They set out to directly sequence the genome of an ancient bacterium—a first for the field—rather than resorting to laborious techniques required in the past to capture degraded ancient DNA.

    Now, online this week in Science, they and their colleagues unveil their success, publishing the complete genome of medieval M. leprae from direct shotgun sequencing (http://scim.ag/VSchuenemann). They were able to get 100 copies on average of each of the 3.3 million bases in the microbe's genome, far better than the 20 copies on average that is the standard for modern bacterial genomes. "We could just reconstruct the genome from scratch," Krause says. "It was like creating a reference genome from an ancient DNA source."

    The breakthrough is all the more amazing because researchers have yet to sequence the M. leprae genome directly from living humans with leprosy. The bacteria cannot be grown in cell culture, so researchers infect armadillos and mice with human M. leprae to get enough to sample for sequencing.

    This technical triumph would have been unheard of 5 years ago. It reflects the turbo boost that the small but energized field of ancient DNA research has gotten from next-generation sequencing machines, invented for the human genome, plus clever new techniques to extract target DNA from a soup of ancient molecules. Krause's team got lucky in their sample, but even those with more modest amounts of ancient DNA are succeeding at nabbing pathogens. "We've had incredible advances with genetic sequencing," said Charles Nunn, an evolutionary geneticist at Harvard University, in April at a symposium on the evolution of infectious disease at the American Association of Physical Anthropologists meeting in Knoxville. "It's critical for understanding the relationships between circulating pathogens today and those in our past."

    Awash in data, several labs are racing neck-and-neck to cull DNA from a Most Wanted list of legendary killers: tuberculosis (TB), plague, cholera, Leishmania, leprosy, the potato blight, and AIDS. They gather traces of these culprits from ancient teeth, bones, hair, feces, and—in the case of potato blight—from skin and leaves, then unleash the sequencers. The work, which began in earnest 3 years ago, adds a new dimension to our understanding of historical events, revealing the true nature of the villains responsible for humanity's worst epidemics. "There are a lot of diseases described in the historical record that we don't know what the pathogen is," says molecular anthropologist Anne Stone of Arizona State University, Tempe.

    The research is also illuminating where pathogens first infected humans and how they have become more virulent, or less, over time. For example, knowing if urbanization long ago triggered the evolution of nastier TB strains "could inform the best strategy for vaccination and drug treatment" in today's increasingly urbanized world, says biomolecular archaeologist Terence Brown of the University of Manchester in the United Kingdom.

    Disease detective.

    Verena Schuenemann extracts ancient DNA from the remains of victims of the plague and other scourges.

    CREDIT: JOHANNES KRAUSE/UNIVERSITY OF TËBINGEN

    The problem with PCR

    None of this was thought possible in the early 1990s, when Stone was a graduate student. She was trying to spot genetic markers for ancient smallpox and TB, working in the lab of Svante Pääbo at the Max Planck Institute in Munich (now in Leipzig). The research was challenging—pathogen genomes are 1000 times smaller than human genomes and can resemble those of garden-variety soil microbes. Back then, researchers were excited if they could sequence a handful of DNA markers from fossils, using the painstaking polymerase chain reaction (PCR).

    Stunning find.

    A tooth from a 14th century Danish woman had more DNA from the leprosy microbe than from her own genome.

    CREDIT: BEN KRAUSE-KYORA

    But Stone couldn't even nab a few snippets. She tried to amplify the Variola major virus that causes smallpox from a 400-year-old mummy from Naples, Italy, but got nothing. She gave up on ancient pathogens and worked on ancient DNA from skeletal remains and the evolution of apes and humans.

    As the years passed, other teams announced having used PCR to ferret out TB from skeletal remains, but critics worried that the evidence was contamination. Even when they could confirm ancient TB, PCR studies shed no light on how ancient TB strains are related to today's M. tuberculosis, because they couldn't get enough ancient DNA to reveal differences between strains. "I don't care if someone says they got TB from a 15,000-year-old sample," says evolutionary biologist Thomas Gilbert of the University of Copenhagen. "I want to know, what can you tell me about that TB?"

    The advent almost a decade ago of high-throughput sequencing machines eventually revolutionized the field. While PCR can copy only DNA fragments that are at least 80 bases long, the new machines decode each base separately: a boon for ancient DNA, which is often recovered in fragments smaller than 80 base pairs. The sequencers opened a whole new world of ancient genomes, including sensational reports of DNA recovered from ice age mammoths, bears, and extinct humans such as Neandertals and Denisovans (Science, 26 August 2011, p. 1084).

    That work drove the development of new "targeted enrichment" methods to extract more ancient DNA from precious fossils. With Pääbo, Krause used one such an approach to sequence the Neandertal genome (Science, 7 May 2010, p. 723). That got him thinking of scaling a new peak: DNA from old pathogens.

    Fishing for genomes

    No. 1 on the Most Wanted list was the agent of the Black Death, or bubonic plague, which wiped out up to half of Europe's population between 1347 and 1351. Historic documents described buboes—swelling in the groin and armpits—resembling those caused by the bacterium Yersinia pestis. Today, this bug infects a few thousand people a year in Africa and Asia and is endemic in prairie voles in the southwestern United States. Even before antibiotics, Y. pestis hardly seemed potent enough to claim millions of lives, so some historians doubted that it was the force behind the Black Death. Early PCR results from medieval victims found markers for part of a gene from modern Y. pestis, but the charges didn't stick: The results couldn't be replicated.

    In 2011, researchers turned to targeted enrichment. Hendrik Poinar of McMaster University in Hamilton, Canada, working with Sharon DeWitte of the University of South Carolina and McMaster graduate student Kirsten Bos, extracted DNA from teeth and bones from the East Smithfield burial ground in London, where plague victims were buried in the 14th century. Working with Krause and Schuenemann, the two labs used "bait"—short DNA segments found in modern Y. pestis—as probes to fish out corresponding stretches of ancient sequence. The researchers rinsed away DNA that didn't bind to the modern bait. This let them snare not only matching sequences, but also DNA in flanking regions that might vary from the modern genome. By scouring overlapping DNA segments over and over, they reported in Nature in 2011, they gathered 30 copies on average of each nucleotide.

    Written in bone.

    DNA from TB lesions on a 19th century teenager's rib bones (right) revealed the strain that infected her. TB deformed this 13th century teenager's spine.

    CREDITS: GEORGE ROBERT MILNER/ILLINOIS STATE MUSEUM; (INSET) A. BOUWMAN ET AL., PNAS 109, 45 (22 OCTOBER 2012)

    This outstanding resolution confirmed that the London plague victims were infected with Y. pestis. To the team's surprise, the genome of the 14th century Y. pestis was remarkably similar to the modern one—a puzzle because it suggests that the same bacterium was far more lethal in the 14th century than it is today. Now, the team is exploring whether the high mortality rate was caused, for instance, by one of the few differences in the genetics of the ancient strain, or by the poor health of medieval victims.

    Work by several groups on ancient and modern samples is laying bare the origin and evolution of the Black Death strain. Researchers assumed that the plague was caused by a new strain that reached Europe in 1347, soon after its emergence. But in November, Krause and colleagues reported in PLOS ONE that the Black Death strain originated in an earlier burst of diversification. By comparing plague DNA from ancient and modern collections worldwide, they found 11 strains circulating at the time of the Justinian Plague in Europe in the 6th to 8th century C.E., including the strain that later caused the Black Death.

    This fits with another team's study of more than 100 strains of Y. pestis from modern humans and rodents in Asia. Yujun Cui of the Beijing Institute of Microbiology and Epidemiology and his colleagues used the modern samples to trace the origin of many strains, including the one that caused the Black Death, back to a "big bang" of diversity around the time of the Justinian Plague, as they reported last year in the Proceedings of the National Academy of Sciences (PNAS). The analysis shows a starlike pattern of evolution, with a burst of new strains of Y. pestis appearing in short order.

    Such a pattern is predicted by a population genetics model created by Francois Balloux of University College London. In his model, new strains of Y. pestis rapidly appeared during epidemics when humans on the move, such as Crusaders or other soldiers, spread the disease into new regions. There, the pathogens went on a tear in new hosts. When the Black Death waned in 1351, the culprit strain replicated less often and its mutations became "fixed," or stable, which is why it is so similar to today's strain, Balloux says.

    Detailed analysis and modeling of the ancient killer may clue researchers in to what's happening when a new pathogen emerges—and how to combat it. The technological advances have also spurred many young researchers to visit Krause's lab in Tübingen, at a rate of one every 2 weeks, to learn targeted enrichment. "It's important to share the methods to raise the quality to these new standards," Krause says. "Otherwise, people would still publish papers with PCR evidence, like they've been doing the past 20 years."

    TB or not TB?

    TB is the second deadliest infectious disease in the world, after HIV; in 2011, it killed 1.4 million people. In the past decade, researchers have revised their view that all human TB infections are caused by almost identical strains of M. tuberculosis. Now, they recognize that there are seven distinct groups of TB strains, with two found only in Africans or recent African immigrants (suggesting an African origin of the disease).

    TB and humans go way back: The earliest archeological evidence comes from a 7800-year-old skeleton found in a cave in Liguria, which has tubercular damage to its spine. The earliest historical records date to 4700 B.C.E., in China. As a result of co-evolution with humans and other animals for many millennia, groups of strains have evolved separately in the Old World (Africa, Europe, and Asia) and in the New World (the Americas). Researchers are eager to understand how New World and Old World strains are related to each other and to animal strains and how the movements of infected humans altered TB's virulence. They'd also like to know whether drug resistance develops at the same sites in different strains and how quickly.

    Famine starter.

    An extinct strain of a funguslike pathogen devastated Ireland's lumper potato crop in the mid-19th century.

    CREDITS (LEFT TO RIGHT): ILLUSTRATED LONDON NEWS/STRINGER/GETTY IMAGES; © NIGEL CATTLIN/VISUALS UNLIMITED/CORBIS (2)

    Answers may lie in the depths of time. Stone and graduate student Luz-Andrea Pfister have already shot down the old notion that humans first acquired TB from cows; it turns out that we gave it to them (Science, 2 May 2008, p. 608). Recent work following the trail of modern strains back to a common ancestor suggests that TB may have been infecting hominids in Africa as long as 3 million years ago.

    No one has yet sequenced a complete ancient M. tuberculosis genome, but researchers are making headway. Last year, a team sampled TB lesions on the rib of a teenage girl who was buried with her twin sister sometime between 1840 and 1911 in St. George's Crypt in Leeds. In a clean room at the University of Manchester, Brown and his former postdoc Abigail Bouwman, now at the University of Zurich, used next-generation sequencers and targeted enrichment, deploying 500 baits to fish out 218 single-nucleotide polymorphisms (SNPs) known to vary among modern TB strains. By analyzing the presence or absence of those SNPs in ancient and modern strains, they compiled the first set of DNA markers for a historic TB strain.

    Comparing the historic strain with the same regions of all seven human strains and 10 animal strains, the team found that the girl from Leeds had a strain uncommon today but virtually identical to one isolated from a patient in New York in 1905. The finding vividly shows how pathogens could traverse great distances well before air travel. "There were a lot of people moving across the Atlantic—a lot of immigration to the U.S.," Brown says. It also shows that the strain was replaced by new ones in 100 years. Because the twin girls came from a family who could afford to bury them in a crypt, the find supports a long-held view, based on historical documents, that TB "was the scourge of the middle class" in the expanding cities, Brown says.

    The complexities of TB in living people mean that data on ancient strains are extremely valuable, says molecular epidemiologist Sebastien Gagneux of the Swiss Tropical and Public Health Institute in Basel. He has proposed that TB has been co-evolving with humans and our ancestors for so long that people from different continents are more susceptible to particular strains. He reported in PNAS in 2006, for example, that U.S.-born patients of Chinese and Filipino ethnicity tend to harbor the same TB strains as patients born in China and the Philippines, respectively—and that it was harder for them to become infected with strains circulating in their adopted land. Gagneux is eager to find out where different TB strains evolved and if they continue to infect their historic hosts at a higher rate than other populations. If so, that would have "important implications for tuberculosis control and vaccine development," Gagneux says, because, for example, it could influence which strains are included in vaccines. Stone, meanwhile, is examining whether Paleo-Indians carried TB as they migrated from Asia to the New World.

    Woes of the Irish

    Between 1845 and 1852, more than a million people in Ireland perished when potato crops failed. A million more fled the impoverished land for America and other nations. The nation never fully recovered. Ireland's present population of 4.5 million is less than three-quarters of what it was at the start of the famine.

    Many blame the famine on politics as well as botany—many tons of food were exported from Ireland to England while people starved—but there's no doubt that the potato blight, a funguslike pathogen called Phytophthora infestans, was the chief culprit. Ireland heavily relied on a single variety, the lumper potato, to feed its growing population, and once lumper potatoes became susceptible to the blight, people had few other varieties to fall back on. Even today, potato blights cost farmers worldwide about $6.2 billion a year, on average.

    Most researchers have blamed the Irish potato blight on a P. infestans strain called US-1, which is a direct descendant of a strain responsible for a blight outbreak in North America starting in 1843. This strain predominated worldwide until the late 1970s.

    But it's not the strain that researchers found when they analyzed dried leaves of potatoes and tomatoes collected from Europe and North America between 1845 and 1896 and stored at the Botanical State Collection, Munich, and the Royal Botanic Gardens, Kew. A team led by Kentaro Yoshida of The Sainsbury Laboratory in Norwich, U.K., and Schuenemann got a pleasant surprise when they sequenced DNA from these samples: As with the 700-year-old leprosy samples from Denmark, the potato blight pathogen was so well preserved that they could shotgun-sequence it directly. They reported last month in eLife that the ancient plants were infested with a strain of P. infestans, HERB-1, that is different from all 15 modern strains, including US-1, although it and HERB-1 are closely related. "An extinct strain caused the pandemic in Ireland and Europe," says Krause, a co-author.

    Mystery solved.

    DNA of the leprosy strain infecting armadillos shows that we gave them the disease.

    CREDIT: HEIDI & HANS-JUERGEN KOCH/HEIDIHANSKOCH.COM

    The common ancestor of these strains probably emerged in the Toluca Valley in Mexico, where diverse strains of P. infestans infect wild relatives of the potato, Krause says. HERB-1 presumably reached Ireland by stowing away on ships sailing from the Americas, he says.

    Work in press in Nature Communications confirms and extends this result. Gilbert and colleagues sequenced five European strains of P. infestans, including one from a potato leaf collected in Belgium in 1845, during the first reported outbreak of the blight. Their samples suggest that the pathogen was introduced to Europe more than once, where it found a vulnerable host—lumpers—and took root.

    The potato famine's societal consequences included a flood of immigration from Ireland to the United States—and on this front, too, ancient DNA may soon have a tale to tell. One of the scourges that the Irish faced at the end of their overseas journey was cholera, which ran riot on the East Coast in 1849. Cholera, nicknamed the blue death, brings severe diarrhea and turns a victim's skin blue-gray from loss of fluids. It was first detected in India in 1817, and researchers have long assumed that Irish immigrants introduced it to the United States. Poinar's graduate student Alison Devault is testing that idea with samples of Vibrio cholerae from 19th century samples of intestines, kept in jars in the Mütter Museum of the College of Physicians of Philadelphia. The findings may yield clues to why the Vi. cholerae strain now devastating Haiti is so virulent.

    Medieval scourge

    Now that they have a high-resolution copy of the complete genome of M. leprae, Krause and colleagues have a chance to bore deeper into the dreaded disease, notorious since Biblical times. The disease ravages the skin, peripheral nerves in the hands and feet, and mucous membranes of the nose, throat, and eyes. Today, leprosy is nowhere near as prevalent as it was in medieval times. Just before 1300 C.E., 25% or more of the adult population in Scandinavia, for instance, died with skeletal signs of leprosy, according to molecular archaeologist Ben Krause-Kyora of the University of Kiel in Germany. Even though the disease can be cured with antibiotics, 225,000 new cases appear every year in developing nations, where disfigured patients are often still shunned and in some nations banished to leper colonies.

    After Krause-Kyora sent the medieval leper victim's tooth to Krause for analysis, they compared the ancient M. leprae genome with those of 11 modern strains and found that the bacterium has evolved very slowly. The pathogen from the medieval leper was almost identical to the modern strain that causes leprosy in India, Thailand, Brazil, and the United States.

    The plague bacterium, Y. pestis, also shows evolutionary stasis since medieval times. But the process of spawning strains appears to differ in these two pathogens. Whereas Y. pestis seems to have spun off a cluster of new strains around 600 C.E., M. leprae has apparently continuously generated new strains, at a slower pace. M. leprae's evolutionary diagram looks more like a classic phylogenetic tree, with new strains branching off on occasion, than the star pattern seen in Y. pestis, Bos says.

    Krause's team found that the medieval Scandinavian girl's strain of leprosy probably diverged from a strain found in Iran and Turkey today, suggesting that the ancestral strain originated in Asia. Crusaders or other travelers may have carried it to Europe around 1000 C.E., where it eventually reached Scandinavia. Leprosy finally declined in the 16th century.

    Yet it has persisted: Several million people live with it worldwide, including about 30 to 40 people in the southern United States who contract it every year. Until recently, no one knew how they got it. Then, in 2011, microbiologist Richard W. Truman of the Health Resources and Services Administration's National Hansen's Disease Program in Baton Rouge and his team sequenced leprosy genomes from armadillos, one of the few nonhuman species afflicted by the disease. The team found that 65% of human infections were a distinct TB strain found in most of the infected armadillos. This suggests that they are getting leprosy from armadillos, presumably from handling them. But did armadillos spread the disease to people, or did we give it to the armored mammals first? Schuenemann and Krause report that we're to blame: The striking closeness of the armadillo leprosy strain to the medieval girl's strain suggests it "is of European origin," Krause says.

    Finally, Krause has also found a solution to the mystery that initially baffled him—why was there far more M. leprae DNA than human DNA in an ancient human tooth? He realized that the M. leprae bacterium has a particularly thick cell membrane, rich in fatty acids that repel water and thus damage. If true for other bacteria, this suggests good prospects for tracing some pathogens back beyond the theoretical limit of human DNA resisting degradation: 1 million years. "This could allow us to study bacteria much father back in time," Krause says. Last year, he was hoping for a modest amount of ancient DNA from a medieval tooth. Now, he's imagining sequencing pathogens that plagued our ancestor, Homo erectus, 1 million years ago. In ancient DNA research, what a difference a year makes.

  5. Solid-Earth Science

    Geophysical Exploration Linking Deep Earth and Backyard Geology

    1. Richard A. Kerr

    Big Science came to solid-Earth studies when the $400 million EarthScope program offered a sharper view of the interior that could help geologists; it's working, mostly.

    RALEIGH—Geologists tramping over the volcanic rocks of Montana's Yellowstone or the high Colorado Plateau in the 1960s had little patience with the geophysicists trumpeting what would soon be called plate tectonics. What could seafloor spreading at the bottom of the Atlantic Ocean possibly have to do with the maddeningly complicated jumble of rocks that is North America?, the continental geologists asked.

    Soon enough, however, the geophysicists won them over. Plate tectonics did neatly explain some major geologic features, such as the Appalachian Mountains and the volcanoes of the Pacific Northwest. But 30 years after the plate tectonics revolution, geologists still weren't content. What about fiery Yellowstone in midcontinent, the cryptically elevated Colorado Plateau, or any number of other quirky geologic features that still weren't fitting into the big picture of plate tectonics?

    That's better.

    Seismic data from EarthScope's Transportable Array sharpened existing imaging (left) so that colder (blue) and hotter (red) features in the mantle stand out (right).

    CREDITS (LEFT TO RIGHT): H. BEDLE ET AL., JOURNAL OF GEOPHYSICAL RESEARCH: SOLID EARTH 114 (22 JULY 2009) © 2009 AMERICAN GEOPHYSICAL UNION; B. SCHMANDT ET AL., U. OF NEW MEXICO

    So around the turn of the century, geophysicists decided how they might finally satisfy the geologists. EarthScope, a proposed four-pronged program, would point a geophysical "telescope" inward to bring the subsurface of North America into unprecedentedly sharp focus. A wave of 400 seismometers would roll from coast to coast imaging the deep interior. A net of GPS instruments and a radar satellite would precisely gauge the grinding of plates along the West Coast from Mexico to Alaska. And a single borehole in central California would probe the heart of the threatening San Andreas fault.

    No one could say just what these largely undirected explorations would discover, geophysicists conceded, but explanations for some of geologists' lingering mysteries would surely emerge as geophysicists brought into focus deep details approaching the scale at which geologists work on the surface.

    Ten years on, EarthScope is looking like a good investment. "The amount of very high-quality data and science generated by EarthScope is spectacular," says geophysicist Jean-Bernard Minster of the Scripps Institution of Oceanography (SIO) in San Diego, California. "EarthScope was the right idea. We've learned a lot more about Earth the last 10 years than the previous 30 to 40 years. I can say that because I don't get any money from EarthScope."

    Beneath North America, it turns out, creatures of the deep Earth roam. From a hot, rising, deep-rooted plume fueling Yellowstone to a cold falling "drip" helping unloose the Colorado Plateau, these deep features do indeed shape geology at the surface. Not that all was smooth sailing. Drilling into even tiny earthquakes proved particularly challenging. But as the program's wave of traveling seismometers washes up on the East Coast, the pleasant surprises are far outweighing the shortfalls.

    Going big science …

    From the start, EarthScope was unlike other projects built through the National Science Foundation's (NSF's) Major Research Equipment and Facilities Construction account. At $197 million for construction over 5 years, it was certainly major. But compared with physicists building a gravity wave detector or astronomers an observatory, geoscientists have "a cultural core that is fundamentally different," geophysicist David Simpson, president of the Incorporated Research Institutions for Seismology in Washington, D.C., told the biennial EarthScope National Meeting here last month.

    EarthScope's facility has not one but thousands of instruments of several sorts distributed coast to coast and from the Mexican border to Alaska. There are no EarthScope principal investigators in line for a Nobel Prize, only a community-based management structure. EarthScope data are not held for analysis by a select few, but immediately available to anyone anywhere in the world. And its "scope" will not be scanning the interior for any particular Holy Grail discovery, just looking around.

    "If you have lots of good data," observed seismologist Edward Garnero of Arizona State University, Tempe, "discoveries flow." Those discoveries, researchers reason, will almost certainly help them understand the North American continent and help predict earthquakes and volcanic eruptions as well.

    To get the big picture

    For EarthScope's deepest and broadest look into Earth, seismologists rolled out USArray: 500 seismometers to record seismic waves passing through and altered by the rock beneath North America. Plenty of other seismometers were already in operation, but most were bunched around dangerous, quake-producing faults in the West.

    US Array ($69 million for construction and $88 million for operations so far) took a much broader view using more sophisticated instruments. Researchers spread 100 seismometers evenly across the lower 48 states in a regular grid with 300 kilometers between them. Those would remain where they were installed. But then, hard against the Pacific coast, geoscientists deployed 400 more seismometers in an 800-kilometer-wide swath between the Canadian and Mexican borders with 70-kilometer spacing.

    Got it covered.

    The EarthScope program was intended to sharpen geophysicists' view of the interior by using more uniform and denser instrument networks. GPS stations (yellow circles) gauge building crustal strain. Seismometers allow mantle imaging (triangles: black, green, and red are in use; pink are future and white past transportable sites; blue are in temporary local study networks). Red star is core-drilling site.

    CREDIT: NSF/EARTHSCOPE

    Then they marched this 400-strong Transportable Array (TA) eastward, one station at a time. After a seismometer had been operating 2 years, field engineers would extract it from its half-buried vault on the trailing edge of the TA and reinstall it to the east on the leading edge, one instrument every day or two for 10 years until a 2000-strong instrument grid reaches the Atlantic coast; that should happen in September. Just as more pixels in an electronic camera yield a sharper image, the dense, continent-spanning TA grid would produce clearer views of the subsurface.

    And it's working. "The things being seen are much smaller," Garnero says, by an order of magnitude. And the greater detail is showing that "the mantle is doing stuff." Seismic analyses can construct 3D images of the interior based on how hotter or colder rock slows or speeds up seismic waves from distant quakes. Earlier, fuzzier seismic images had already shown hotter-than-normal rock a few hundred kilometers beneath Yellowstone. But images constructed with the sharper TA data show that the hot rock extends through the upper mantle beneath the North American plate and into the lower mantle at least 900 kilometers down. That is the first rising, hot-rock plume that most seismologists can agree is rooted in the lower mantle (Science, 5 April, p. 22).

    The Yellowstone plume most likely starts at the mantle's bottom, hard against the molten-iron core, but it obviously hasn't had an easy rise. As imaged by seismologist Brandon Schmandt of the University of New Mexico, Albuquerque, and his colleagues, the plume seems to have encountered resistance about 600 kilometers down that created a gap in the plume. The obstacle appears to have been a sheet of tectonic plate that dove into the mantle beneath the western edge of North America tens of millions of years ago and then broke apart. In another study using TA data, seismologist Eugene Humphreys of the University of Oregon in Eugene and his colleagues suggested that the sinking slab broke apart when a chunk of particularly thick descending plate jammed at the continent's edge about 50 million years ago (Science, 14 January 2011, p. 142).

    Indeed, slabs of sunken plate can now be clearly seen dangling here and there around the western lower 48. Schmandt and others have pointed out that sinking slabs would have let hot mantle rock invade the shallow mantle until the hot, melting mantle rock came up against the continental plate. TA's improved seismic images do seem to imply such local mantle upwellings. These often coincide in space and time with major episodes of volcanic outpourings such as the outbursts that formed the Idaho Batholith and the Columbia River flood basalt, suggesting a connection, researchers say.

    And then there are the drips. These are the antiplumes, the bottommost layers of the continental plate that peel away or slough off and sink because they are colder and therefore denser than adjacent mantle. Relieved of the burden, the overlying plate can rise. One drip clearly seen in TA data probably let the southern Sierra Nevada float upward. Using TA data, seismologist Alan Levander of Rice University and colleagues have shown how drips off the bottom of the Colorado Plateau have helped let it rise to its 2000-meter altitude. The current drip has been falling away for the past 6 million years, they find. What with a rising plume, sinking drips, and melting mantle boring into the continent, Humphreys says, "we're remaking continents."

    Probing the plate boundary

    The rest of EarthScope took a broad but exceedingly shallow look at the western boundary of the North American plate, with a single, pinpoint boring into the San Andreas. In addition to the seismic networks of USArray, the 2001 EarthScope Project Plan proposed two components that would focus on the zone from Mexico to Alaska where the Pacific plate grinds by the North American plate. Only one of the proposed components came to pass.

    The Plate Boundary Observatory (PBO) component of EarthScope ($100 million for construction and $58 million for operations so far) consists of 1100 GPS instruments installed in a broad swath of the western United States. They continuously measure their changing position to about 1 millimeter per year. Over the long haul, the two plates are moving by each other at about 30 millimeters per year. But if the plates snag on the San Andreas or on any of the broad maze of faults spanning the plate boundary, the stress would squeeze or stretch the surrounding crust, moving the GPS instruments. All told, PBO GPS continuously records the building strain—or sudden release of strain in quakes—at points separated by tens to hundreds of kilometers.

    A deep grab.

    Workers extract a core from 3 kilometers down in the SAFOD drill hole into the San Andreas fault. The core showed clay weakening the fault.

    CREDIT: NSF/EARTHSCOPE

    Unlike GPS, the second planned geodetic component—a satellite-borne interferometric synthetic aperture radar (InSAR)—would have mapped changing strain everywhere across the plate boundary, not just at widely separated points. An InSAR satellite can gauge the motion of contiguous spots on the surface a few tens of meters across with a precision of a few millimeters. With such spatial continuity, geodesists could have been far more precise about gauging the strain building toward failure on a particular segment of fault, geodesist David Sandwell of SIO told the meeting.

    But a U.S. InSAR satellite with a focus on the western plate boundary was not to be, at least not yet. Although NSF could chip in some seed funding, researchers had to sell NASA on the idea. Minster has been the principal investigator on four InSAR proposals, "none of which worked," he says. "I'm not quite sure why."

    But even without InSAR, EarthScope's PBO has been delivering. PBO observations have revealed the often complex release of quake energy along a fault. PBO strain data are also being fed into calculations of fault-by-fault earthquake hazards that will produce the next Uniform California Earthquake Rupture Forecast gauging risk.

    And it turns out there's more shakin' than the San Andreas. In another bit of EarthScope serendipity, PBO observations have helped reveal a jiggling of the Great Basin of Utah and Nevada. The crust there is stretching east to west over millennia, but GPS is showing that over a few years, a part of the Great Basin can go from extending to contracting or the entire basin can shift to the east or west. Tectonophysicist Brian Wernicke of the California Institute of Technology in Pasadena and colleagues have argued that somewhere tens of kilometers beneath the surface, the rock above is able to slip across the rock below. That would mean the whole system could be responding to the churning of the mantle brought on by the disrupting sunken plate imaged by USArray.

    A hole not far enough

    The final EarthScope component took a far narrower view of North America: down a 15-centimeter-wide hole drilled next to the San Andreas in central California. Planners intended that the $27 million San Andreas Fault Observatory at Depth (SAFOD) would help understand the chemical and physical processes that cause the opposing sides of the San Andreas to quietly slip by each other in some places and stick, build stress, and fail in an earthquake in other places. Those are good things to know if you're wondering about the next Big One.

    So SAFOD workers drilled a hole straight down 1.8 kilometers west of the fault and then angled it to intercept the fault at a depth of just over 3 kilometers. The plan was to punch out cores of rock across the fault and bring them to the surface, along with fault fluids, for analysis. Then workers would lower an instrument package down the hole to monitor fault conditions and to listen to the tiny quakes that pop off nearby.

    Drilling through hard, broken rock is neither easy nor cheap, but SAFOD drillers managed to recover core from a weak section of the fault. Fifty years ago, geologists proposed that clay was lubricating the sides of the fault in such spots so the fault would not stick. Tectonophysicist David Lockner of the U.S. Geological Survey in Menlo Park, California, and colleagues confirmed that idea by showing that clay formed by alteration of the mineral serpentine had rendered the fault there slippery and "profoundly weak."

    SAFOD efforts to understand how and why other fault segments stick and then break did not work out so well. Drilling problems created extra costs, according to SAFOD co-leader Mark Zoback of Stanford University. On top of that, the cost of even routine drilling soared as the growing Chinese economy sucked up raw materials and an oil-drilling boom in North Dakota drove up the cost of leasing a drilling rig. So NSF money for drilling ran out before a nearby stuck patch of fault could be cored. Then a leaky seal wrecked the instrument package days after it was lowered into the hole.

    Still, "overall, I view EarthScope as very successful," says geophysicist Seth Stein of Northwestern University in Evanston, Illinois, excluding the satellite component that was never attempted. He was among the half-dozen researchers who first took the idea for an inward-looking scope to NSF. "Two out of three components were on time and on budget and are doing everything they were supposed to. Two point five out of three ain't bad."

    And it isn't over. The USArray is only just now reaching the East Coast, and then it will be moved on to Alaska. For that matter, seismologists are still swamped by the volume of USArray data and are only beginning to look farther east and even deeper while applying more sophisticated analytical techniques. The mantle aquarium may soon have more inhabitants.

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