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WorldMags
CONTENTS Volume 332 Issue 6025

EDITORIAL BOOKS ET AL.


13 When Science and the Media Mix 39 Intellectual Curiosity and the
Christopher Reddy Scientific Revolution
T. E. Huff, reviewed by S. H. Ali
NEWS OF THE WEEK 40 Transcendent Man
18 A roundup of the week’s top stories B. Ptolemy, Director; reviewed by M. Shermer

NEWS & ANALYSIS POLICY FORUM


22 Scientific Consensus on Great Quake 41 Economic Importance of Bats
Came Too Late in Agriculture
23 In Indus Times, the River Didn’t J. G. Boyles et al.
Run Through It
PERSPECTIVES page 28
24 Pool at Stricken Reactor #4 Holds
Answers to Key Safety Questions 43 Danger, Microbes, and Homeostasis
B. P. Lazzaro and J. Rolff
25 Artificial Leaf Turns Sunlight
Into a Cheap Energy Source 44 Phosphatase Inhibition Delays
Translational Recovery
27 Army Missed Warning Signs R. L. Wiseman and J. W. Kelly
About Alleged Anthrax Mailer >> Report p. 91

NEWS FOCUS 47 An Innate Role for IL-17


M. Dominguez-Villar and D. A. Hafler
28 The Rise of Animal Law >> Research Article p. 65
A Road Map for Animal Rights
>> Science Podcast 48 Impurities Enhance Semiconductor
Nanocrystal Performance
32 Girth and the Gut (Bacteria) Y. C. Cao
>> Report p. 77; Science Podcast
LETTERS
50 Retrospective: George Bugliarello
35 Protecting Invaders for Profit (1927–2011)
S. A. Lambertucci and K. L. Speziale I. Juran and J. Falcocchio
Culturomics: Statistical Traps
Muddy the Data REVIEW
E. E. Morse-Gagné
53 Beyond Predictions: Biodiversity
Culturomics: Periodicals Gauge Conservation in a Changing Climate
Culture’s Pulse T. P. Dawson et al. page 39
T. Schwartz
Response CONTENTS continued >>
E. L. Aiden et al.
Longer Trips Possible for Human Missions
A. Christou
36 CORRECTIONS AND CLARIFICATIONS

COVER DEPARTMENTS
Adult sockeye salmon (weight ~2.5 kg; length ~60 cm) migrating 10 This Week in Science
to spawning grounds in the Adams River, British Columbia, Canada. 14 Editors’ Choice
Sockeye salmon populations in the Fraser River, British Columbia, 16 Science Staff
are physiologically adapted to their specific upriver migration 116 New Products
conditions. In a Report on page 109, Eliason et al. suggest that 117 Science Careers
cardiac adaptations help protect one salmon population from
cardiac collapse at high temperatures.
Photo: Robert Polo; robpolo.photography@gmail.com

WorldMags www.sciencemag.org SCIENCE VOL 332 1 APRIL 2011 5


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CONTENTS

RESEARCH ARTICLES 88 Microtomography of Partially Molten


Rocks: Three-Dimensional Melt Distribution
60 The World’s Technological Capacity
in Mantle Peridotite
to Store, Communicate, and Compute
W. Zhu et al.
Information As mantle rocks melt, an interconnected
M. Hilbert and P. López
network of liquid drives the ascent of
An inventory of the world’s technological magma to the sea floor.
capacity from 1986 to 2007 reveals the
evolution from analog to digital technologies. 91 Selective Inhibition of a Regulatory
Subunit of Protein Phosphatase 1
65 Chronic Mucocutaneous Candidiasis
Restores Proteostasis
in Humans with Inborn Errors
P. Tsaytler et al.
of Interleukin-17 Immunity Guanabenz, a small-molecule inhibitor,
A. Puel et al.
protects cells from lethal accrual of misfolded
Chronic yeast infections in the absence of other proteins in the endoplasmic reticulum.
infections result from genetic deficiencies in >> Perspective p. 44
proinflammatory host responses.
>> Perspective p. 47 94 Directional Switching of the Kinesin Cin8
Through Motor Coupling
J. Roostalu et al.
REPORTS
A molecular motor switches direction upon
69 PAMELA Measurements of Cosmic-Ray interacting with individual microtubules pages 47 & 65
Proton and Helium Spectra or antiparallel microtubules.
O. Adriani et al.
99 The C-Terminal Domain of
Satellite measurements challenge the current
understanding of cosmic-ray acceleration and
RNA Polymerase II Is Modified
propagation in our Galaxy. by Site-Specific Methylation
R. J. Sims III et al.
72 Spontaneous Ferroelectric Order The expression of small nuclear RNAs and
in a Bent-Core Smectic Liquid Crystal small nucleolar RNAs is regulated by
of Fluid Orthorhombic Layers modification at a single arginine residue.
R. A. Reddy et al.
103 Perception of UV-B by the Arabidopsis
The ferroelectric properties of bent-core
liquid crystalline molecules emerge from
UVR8 Protein
L. Rizzini et al.
ordering within the smectic layers.
A plant ultraviolet-B photoreceptor uses a
77 Heavily Doped Semiconductor tryptophan-based chromophore.
Nanocrystal Quantum Dots
106 Bacteria-Phage Antagonistic Coevolution
D. Mocatta et al.
Impurities can be added into semiconductor
in Soil
P. Gómez and A. Buckling
nanoparticles to control their electronic and page 72
optical properties. Microcosm experiments show endless cycles
of host and parasite adaptation in near
>> Perspective p. 48; Science Podcast
natural populations.
81 Electrochemically Mediated Atom Transfer
109 Differences in Thermal Tolerance Among
Radical Polymerization
Sockeye Salmon Populations
A. J. D. Magenau et al.
E. J. Eliason et al.
The structure of a polymer can be fine-tuned
Environmental conditions encountered during
by rapidly starting and stopping its synthesis.
migration shape cardiorespiratory physiology
84 Thermochronometry Reveals Headward in sockeye salmon.
Propagation of Erosion in an Alpine
Landscape CONTENTS continued >>
D. L. Shuster et al.
Glacial troughs in New Zealand mountains
developed by propagation of erosion
up valleys.

page 88

WorldMags www.sciencemag.org SCIENCE VOL 332 1 APRIL 2011 7


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Moving science forward

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CONTENTS

SCIENCEONLINE
SCIENCEXPRESS SCIENCESIGNALING SCIENCETRANSLATIONAL MEDICINE
www.sciencexpress.org www.sciencesignaling.org www.sciencetranslationalmedicine.org
Saturn’s Curiously Corrugated C Ring The Signal Transduction Knowledge Environment Integrating Medicine and Science
M. M. Hedman et al. 29 March issue: http://scim.ag/ss29Mar2011 30 March issue: http://scim.ag/stm033011
10.1126/science.1202238 EDITORIAL GUIDE: Focus Issue—Rendering COMMENTARY: The Precompetitive Space—
The Impact of Comet Shoemaker-Levy 9 Resistance Futile Time to Move the Yardsticks
Sends Ripples Through the Rings of Jupiter E. M. Adler and N. R. Gough T. Norman et al.
M. R. Showalter et al. Understanding the pathways that mediate drug A recent meeting of minds set into motion an
Spacecraft observations show that Saturn’s resistance is key to developing new cancer therapies. open-access initiative designed to achieve proof
and Jupiter’s rings preserve records of recent of clinical mechanism for selected disease targets.
RESEARCH ARTICLE: Amplification of the Driving
interplanetary debris collisions. Oncogene, KRAS or BRAF, Underpins Acquired PERSPECTIVE: Human Pluripotent Stem Cells—
10.1126/science.1202241 Resistance to MEK1/2 Inhibitors in Colorectal Decoding the Naïve State
Topological Phase Transition and Texture Cancer Cells W. Li and S. Ding
A. S. Little et al. Human stem cells exist in functionally distinct states
Inversion in a Tunable Topological Insulator
that must be deciphered before these versatile
S.-Y. Xu et al. PERSPECTIVE: Resistance to MEK Inhibitors— reagents can be used to transform medicine.
Two types of bulk insulator are realized in the same Should We Co-Target Upstream?
family of compounds through chemical doping. P. I. Poulikakos and D. B. Solit
RESEARCH ARTICLE: A MEK Inhibitor Abrogates
10.1126/science.1201607 Amplification of an upstream kinase in a three-kinase Myeloproliferative Disease in Kras Mutant Mice
module confers resistance to cancer drugs that target N. Lyubynska et al.
Protein Tyrosine Kinase Wee1B Is Essential
a downstream kinase. Inhibiting the Raf/MEK/ERK pathway reverses the
for Metaphase II Exit in Mouse Oocytes harmful effects of oncogenic Kras on hematopoietic
J. S. Oh et al. RESEARCH ARTICLE: c-MYC Suppresses BIN1 differentiation, suggesting a strategy for treating
Cyclin degradation is not the only mechanism that to Release Poly(ADP–ribose) Polymerase 1— myeloproliferative neoplasms.
controls the exit of mouse oocytes from meiosis. A Mechanism by Which Cancer Cells Acquire
10.1126/science.1199211 RESEARCH ARTICLE: Use of Mutant-Specific Ion
Cisplatin Resistance Channel Characteristics for Risk Stratification
Proteoglycan-Specific Molecular Switch S. Pyndiah et al.
of Long QT Syndrome Patients
for RPTPσ Clustering and Neuronal Extension PERSPECTIVE: MYC, PARP1, and C. Jons et al.
C. H. Coles et al. Chemoresistance—BIN There, Done That? Mutations that slow the opening of potassium channels
One receptor binds two different types S. Ganesan in the heart can predict risk for long QT syndrome, a
of proteoglycan at the same site but with c-MYC promotes cisplatin resistance by enabling heart arrhythmia that can cause sudden death.
divergent outcomes. the increased activity of a DNA repair enzyme.
10.1126/science.1200840
RESEARCH ARTICLE: Global Phosphoproteomics SCIENCEPODCAST
Reveals Crosstalk Between Bcr-Abl and Negative www.sciencemag.org/multimedia/podcast
SCIENCENOW
Feedback Mechanisms Controlling Src Signaling Free Weekly Show
www.sciencenow.org On the 1 April Science Podcast: semiconductor
L. Rubbi et al.
Highlights From Our Daily News Coverage nanocrystals, nonhuman rights, your Letters to
PODCAST Science, and more.
Damping Down Fear With Cortisol
T. G. Graeber and A. M. VanHook
The stress hormone enhances therapy
Negative feedback fails to limit Src family kinase
to treat a phobia of heights.
activity in the presence of Bcr-Abl, an oncoprotein
SCIENCEINSIDER
http://scim.ag/less-fear news.sciencemag.org/scienceinsider
that drives leukemia.
Sensing Organ Rejection Science Policy News and Analysis
A new DNA test aims to detect when the body SCIENCECAREERS
rejects a transplanted organ. www.sciencecareers.org/career_magazine
http://scim.ag/organ-test
Free Career Resources for Scientists
Spinning the Sun’s Rays Into Fuel SCIENCE (ISSN 0036-8075) is published weekly on Friday, except the last
Experimental Error: Achieving Immortality
Artificial leaf makes fuel production possible week in December, by the American Association for the Advancement of
A. Ruben Science, 1200 New York Avenue, NW, Washington, DC 20005. Periodicals Mail
wherever there’s water. postage (publication No. 484460) paid at Washington, DC, and additional mailing
How can we ensure that future students will read our
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Reader’s Guide to Periodical Literature and in several specialized indexes.

WorldMags www.sciencemag.org SCIENCE VOL 332 1 APRIL 2011 9


EDITED BY STELLA HURTLEY

How Much Information Down in the Valley >>


Is Out There? Breathtaking alpine landscapes illustrate the
In the past 20 years, there have been dramatic powerful nature of glacial erosion. The balance
changes in the world’s ability to generate, com- of climate-related forces on the topography and
municate, and store information. Hilbert and height of mountains is generally measured by
López (p. 60, published online 10 February) the rate of erosion relative to the rate of uplift,
conducted a survey of 60 categories of analog but uncertainties related to field measurements
and digital technologies during the period from compared to models have obscured the gen-
1986 to 2007 and observed their changing con- eral mechanisms. Shuster et al. (p. 84) com-
tributions to global informational capacity. The bined these two approaches on the mountains
capacity estimates took into account improve- of Fiordland, New Zealand, to tease out these
ments in hardware performance and in software- interrelationships. Isotopic dating suggests that
based compression rates. The revolution in erosion due to glacial activity removed most of
digital technology appears to have sustained an the landscape that was older than 2.5 million
exponential increase in the global capacity to years. Combined with a landscape evolution
process information. model, the results suggest that the modern to-
pography of the region formed as the result of
successive advances of erosion up valleys.
Genetics of Candidiasis
Chronic mucocutaneous candidiasis disease
(CMCD) is characterized by chronic or recur-
ring infection with Candida albicans and, to a sity consequences of climate change and to one of the oxidation states, this modulation suc-
lesser extent, with Staphylococcus aureus. The build conservation actions around the natural cessively triggered and halted polymerization,
underlying cause of CMCD is unknown. Puel et mechanisms that have allowed species to persist facilitating precise control of chain structure.
al. (p. 65, published online 24 February; see the through environmental changes in the past.
Perspective by Dominguez-Villar and Hafler)
now report two genetic etiologies associated with
The Melt Also Rises
CMCD. The first is an autosomal recessive muta-
Cosmic Complications The hot liquid rock that seeps out of mid-ocean
tion in interleukin 17 (IL-17) receptor A, which Earth is constantly bombarded by cosmic rays— ridges makes its way through the oceanic
prevents its expression. The second is an autoso- subatomic charged particles (mostly protons and crust when the solid mantle below rises and
mal dominant mutation in the cytokine IL-17F, helium nuclei) that are thought to be accelerated depressurizes. Understanding the initial stages
which partially reduces its activity. Thus, human in the shock waves produced by stellar explosions. of melt formation and migration, however, has
IL-17–mediated immunity is required for protec- Using data from the satellite-borne PAMELA ex- been based on indirect seismic measurements
tion against these mucocutaneous infections. periment, Adriani et al. (p. 69, published online or limited experimental approaches. Zhu et al.
3 March) report spectral differences between (p. 88) collected three-dimensional images of
protons and helium in cosmic rays. The results do melting mantle rocks using x-ray synchrotron
Conservation: Learning not match predictions from models of cosmic-ray microtomography. The images reveal the forma-
acceleration and their subsequent propagation tion of an interconnected melt network at the
from the Past through our Galaxy, suggesting that more com- scale of single mineral grains with a continuous
The consequences of climate change are now plex processes need to be considered. increase of flow velocity of melt in partially

CREDITS (TOP TO BOTTOM): JOHNNY SANDERS; WWW.GRAMBOPHOTO.COM


being taken seriously by conservation bodies molten rocks. Melt is thus extracted from the
and governments, just as information from mantle as a function of the properties of the
fossil, historical, and present-day studies is
Charging Ahead liquid (for example, viscosity and melt fraction)
providing new insights into how different species Polymerization resembles a chemical reaction and not because of a shift in the porosity or
have responded, and could respond. Dawson run amok; instead of forming a single discrete permeability of the ocean crust.
et al. (p. 53) review product, reagents latch on to one of a slew of
evidence that points to growing chains, which in turn can latch on to
a need to move beyond each other. Some semblance of order can be
Stress Relief
predictions based solely imposed in a so-called living process, in which The reversible phosphorylation of proteins al-
on niche models, because catalysts or mediators keep all the chains in the lows cells to adapt to sudden changes in their
these models neglect system at more or less the same length through- environment. Tsaytler et al. (p. 91, published
many biological differ- out the growth period. Magenau et al. (p. 81) online 3 March; see the Perspective by Wiseman
ences between species. used electrochemistry to introduce a finer level and Kelly) describe a specific small-molecule
The emerging challenges of control. Varying an applied bias allowed for inhibitor of a regulatory subunit of protein
are to find alternative rapid modulation of the oxidation state of a phosphatase 1, guanabenz. Guanabenz selec-
ways of anticipating and copper polymerization catalyst through charge tively bound to a regulatory subunit of protein
managing the biodiver- transfer. Because the catalyst is only active in phosphatase 1 and selectively disrupted the

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10 1 APRIL 2011 VOL 332 SCIENCE www.sciencemag.org
This Week in Science
INTRODUCING
stress-induced dephosphorylation of a subunit of translation initiation factor 2, thereby prolonging
translation attenuation in stressed cells. This favored protein folding, promoting resistance to protein
AAAS
misfolding in the endoplasmic reticulum. MemberCentral
Molecular Motor
In most eukaryotes, spatial reorganization of the microtubule cytoskeleton during cell division de-
pends crucially on microtubule cross-linking motors of the kinesin-5 family. Roostalu et al. (p. 94,
published online 24 February) combined in vitro and in vivo experiments to examine Cin8, a mitotic
kinesin-5 from budding yeast. Single fluorescent molecule imaging and microtubule-sliding assays
on chemically functionalized surfaces, as well as in vivo imaging revealed that Cin8 is a bidirectional
motor, unlike any other kinesins. Surprisingly, the “default directionality” of this motor was opposite
to that of other kinesin-5 proteins. However, the motor was able to switch directionality, depending
on whether it was working alone on individual microtubules or as a member of a team between an-
tiparallel microtubules, like those found in the mitotic spindle. Cin8 may thus regulate directionality
by sensing the motor-microtubule configuration.

Nanoparticle Doping
The deliberate introduction of impurities into semicon-
ducting materials is used to control their electrical prop-
erties and forms the basis of modern electronics. When The exclusive new
considering nanometer-sized particles, the addition of website for the AAAS
only a few defect atoms can make the particle highly member community.
doped. However, forcing the foreign atoms into the
nanoparticle is a challenge. Mocatta et al. (p. 77; see
the Perspective by Cao) developed a method to add Cu,
Ag, or Au impurities into InAs nanocrystals, which will be important in the fabrication of highly ef-
ficient, quantum dot–based electronic devices such as photovoltaic cells and light-emitting diodes.

Plant Ultraviolet Perception


Numerous plant photoreceptors act in the visible wavelengths of light. Now, Rizzini et al. (p. 103) AAAS MemberCentral is a new
report the discovery of a plant ultraviolet (UV)–B photoreceptor with distinctive mechanistic features. website focused on helping you
The plant UV-B photoreceptor, the Arabidopsis UVR8 protein, used a specifically positioned aromatic —the scientists, engineers, educa-
amino acid, tryptophan, as its chromophore. The UV-driven monomerization of UVR8 dimers sig- tors, students, policymakers, and
naled receptor activation. Furthermore, this plant UV perception system could be transplanted into concerned citizens who make up
yeast and mammalian cells. the AAAS community—connect. You
can contribute to discussion groups
Real-World Coevolution or blogs, participate in a webinar, or
share photos of your field research.
In test-tube experiments using bacteria and their viruses, “arms races” evolve between hosts and
You can exchange ideas, learn
parasites. Gómez and Buckling (p. 106) took genetically tagged bacteria and their respective
phage and developed an experimental system in which soil microcosms containing a background about your fellow members, and
microbial community were inoculated with the tagged microbes. Over time and locally in space, gain fresh insights into issues that
bacteria became resistant to coexisting phage. But resistance is more costly in terms of reproductive matter to you the most. Experience
capacity in soil compared with the lab, and so the bacteria did not maintain resistance to past strains MemberCentral for yourself.
of phage. Similarly, neighboring strains of phage could not infect bacteria in other neighborhoods.
Thus, in the wild, bacteria and phage rapidly coevolve. Visit MemberCentral.aaas.org today.
Log in using your Science online
username and password.
It Takes Heart
The once-in-a-lifetime migration of sockeye salmon from the sea to their natal spawning grounds
subject fish to extremely challenging physical conditions. These conditions are variable—fish that
CREDIT: MOCATTA ET AL.

spawn in coastal tributaries have much easier journeys than those who traverse up-river for many
weeks. Eliason et al. (p. 109) examined eight salmon populations that experienced a variety of
migration conditions within the Fraser River in British Columbia, Canada. The fish with the most
challenging journeys possessed the largest hearts and the best-developed cardiorespiratory system.
Thus, local selective regimes have driven physiological adaptation to differing migratory conditions. MemberCentral.aaas.org

WorldMags www.sciencemag.org SCIENCE VOL 332 1 APRIL 2011


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EDITORIAL

When Science and the Media Mix


Christopher Reddy is a AS THE DEVASTATING IMPACTS OF JAPAN'S EARTHQUAKE AND TSUNAMI CONTINUE TO UNFOLD, AND
senior scientist and the concern over the Fukushima nuclear power plant grows, communication between scientists
director of the Coastal and the media has never been more vital. Fourteen years ago, journalist Jim Hartz and physi-
Ocean Institute, Woods cist Rick Chappell warned in their book Worlds Apart: How the Distance Between Science
Hole Oceanographic and Journalism Threatens America's Future that people are dangerously unenlightened about
Institution, MA. E-mail: science's role in many aspects of life and society, in part because of the inability of scientists
creddy@whoi.edu. and journalists to understand each other. Today's relentless 24-hour media news cycle and
blogosphere offer ample opportunities for both parties to provide politicians, policy-makers,
and the public with scientific knowledge needed to inform their opinions and decisions. Yet the
communication gap continues.
As a marine scientist who studies oil spills, I was in the fray after the Deepwater Horizon
oil spill in the Gulf of Mexico last year. Journalists and scientists tried
hard to communicate with each other, but I saw messages that were
not delivered well to the media and/or misinterpreted by the media.
In interviews, I made reference to my research on a 1969 oil spill in
Falmouth, Massachusetts, which showed that oil continues to affect
a small coastal marsh area, but did not anticipate many journalists’
response: They extrapolated these remarks to infer potential dire, long-
lasting impacts of the Gulf spill on marshes. I tried to restore perspec-
tive and reinforce that many oiled marshes have rebounded in the past,
and that not all oil spills or coastal marshes are alike, but it was too late.
That critical point was either missed or overlooked.
Such mistakes caused emotional damage to those living in the Gulf
area, leaving people with more stress than knowledge. The research and
impacts of the spill are still unfolding, and despite people’s yearnings,
there probably won’t be quick or clear-cut answers. Nevertheless, this
is no time for scientists to run back into the ivory tower and pull up the drawbridge. Scientists
have to do a better job of communicating not just what they know, but also what they don’t know,
and what is uncertain. At their best, science and journalism both research exhaustively, discover
CREDITS: (TOP) TOM KLEINDINST/ WOODS HOLE OCEANOGRAPHIC INSTITUTION; (RIGHT) SSPL/GETTY IMAGES

knowledge, and communicate it accurately and objectively. For years, I have invited journal-
ists to my laboratory to learn about field work and chemical analysis. We have defined terms,
traded metaphors, and explained the perils and protocols of scholarly publishing and publish-
ing for the public. Both parties have benefited. Journalists have come away with a greater
appreciation of the research world and an increased ability to responsibly report to the public,
and I have a better idea of the questions people want answers to.
How can scientists start to engage the media? Universities and colleges have press offices,
but most scientists only interact with them when they have a high-profile manuscript or an
inquiry from the press. However, the press office can be an invaluable conduit for explaining
research to the media. In addition, scientists can reach out to general reporters and invite them
into a conversation about the challenges that both parties face on a daily basis. Scientists also
can encourage their institutional leaders to invest, even modestly, in outreach to the journal-
ism community in the form of briefings, Web sites, and workshops. Fellowship programs such
as those at the Woods Hole Oceanographic Institution, Marine Biological Laboratory, and the
University of Rhode Island get journalists into laboratories and in the field alongside scientists
for a week or more, experiences that are well worth the investment.
Communicating is risky, but not doing so is riskier. If scientists and journalists don’t
try harder and make continual efforts to learn each other’s languages and gain confidence,
knowledge will remain locked in laboratories, misunderstood, unused, or even worse, mis-
used. When this happens, those who thirst for information are shortchanged, and the work
of scientists becomes more of an interesting hobby than a critical endeavor of fundamental
value to society. – Christopher Reddy

10.1126/science.1205172

WorldMags www.sciencemag.org SCIENCE VOL 332 1 APRIL 2011 13


EDITORS’CHOICE
EDITED BY KRISTEN MUELLER AND JAKE YESTON

MICROBIOLOGY

TB Tolerance Exposed
One of the reasons tuberculosis (TB) continues to be a substan- ment of drug tolerance. Multidrug-tolerant bacteria were pres-
tial public health problem is because the bacteria that cause TB, ent in macrophages just days after infection and were expanded
Mycobacterium tuberculosis, develop drug tolerance quickly. and disseminated by granulomas. Bacteria acquired tolerance by
This requires patients to follow a 6-month-long drug regimen replicating in macrophages, in both fish and mammalian cells.
to ensure bacterial eradication, to which many patients fail to Upon infection, macrophages increased expression of bacterial
adhere. In order to identify new drug targets that may lead to efflux pumps, which can pump drugs out. Use of pump inhibitors
shorter therapeutic regimens, Adams et al. dissected the devel- demonstrated that these complexes mediated drug tolerance. To-
opment of drug tolerance in a zebrafish model of TB. Zebrafish gether, these studies suggest that adding efflux pump inhibitors
infection with Mycobacterium marinum followed a similar disease to the standard TB therapies may be an effective way to reduce
course as human infection, which included the rapid develop- the course of treatment. — KLM
Cell 145, 1 (2011).

BIOCHEMISTRY helicases loaded onto DNA could then move however. In order to learn more about these
apart, leaving the extruded DNA between them positions, Bush et al. surveyed SFES and non-
How to Unwind
accessible for replication. — VV SFES faculty members within the California State
During DNA replication, ring-shaped helicases Nat. Struct. Mol. Biol. 18, 10.1038/ University System (CSU). Despite SFES existing
use energy from ATP hydrolysis to move along nsmb.2004 (2011). across all science disciplines, faculty ranks, and
and separate DNA strands, creating space for CSU campuses, their role is still not well defined.
new bases to be added to the emerging template. E D U C AT I O N SFES reported teaching the same amount as
Initiation of replication in eukaryotes involves their non-SFES peers, and the same propor-
two key steps. First, the double hexamer Mcm2-
Sizing Up Education Specialists tion of SFES reported being engaged in science

CREDITS (TOP TO BOTTOM): ADAPTED FROM ADAMS ET AL., CELL 145, 1 (2011); ISTOCKPHOTOS.COM
7 helicase is loaded onto duplex DNA. Second, Attempts to include education training into education research as reported being engaged
Cdc45 and GINS associate with each hexamer already demanding science faculty schedules in basic science research. Although SFES had
to form the active CMG helicase. To gain insight have been challenging. One solution is the formal education training, the amount of actual
into these two steps, Costa et al. determined the introduction of Science Faculty with Educa- training reported was minimal, which suggested
structures of Mcm2-7 and the full CMG helicase tion Specialties (SFES), scientists who take on that science departments still prefer to hire sci-
by single-particle electron microscopy. Structural education roles, into science departments. entists trained in basic research. The majority of
models of Mcm2-7 showed a ring that was open This may increase support for faculty develop- SFES thought that they are making a difference;
between Mcm2 and Mcm5 and could either be ment and innovation in teaching and increase however, almost 40% were considering leaving
planar or form a slight spiral. The full helicase departmental interest in research on teaching their positions because of concerns that their
was constrained to the planar conformation, and learning. Minimal data are available on work in education was not supported, valued, or
and GINS and Cdc45 bridged the gap to form a the purpose, structure, and outcomes of SFES, understood. — MM
large channel. Imaging of CMG purified in the CBE Life Sci. Educ. 10, 25 (2011).
presence of an ATP analog revealed a conforma-
tional change induced by nucleotide binding; CELL BIOLOGY
the gap between Mcm2 and Mcm5 closed and
the channel was divided into two smaller pores.
A Less Toxic Treatment
The tendency of Mcm2-7 to form open rings Cells frequently tag proteins that are targeted for
might facilitate loading onto duplex DNA. Upon destruction by the proteasome with ubiquitin, a
binding of Cdc45 and GINS, the structural process that is important for maintaining cellular
data are consistent with a model in which CMG homeostasis and health. Besides defunct or aber-
promotes duplex opening and accommodates rant cytosolic proteins, misfolded endoplasmic
a single strand in each of its pores. The two reticulum–derived proteins are “dislocated” back

WorldMags
14 1 APRIL 2011 VOL 332 SCIENCE www.sciencemag.org
EDITORS’CHOICE

into the cytosol, ubiquitinated, and degraded greatly affected the hydrology of streams and
by the proteasome. Proteasome inhibitors that rivers. However, Native Americans had been
block various stages of these processes exist and practicing agriculture and forest management
are useful for studying this biological process, for several centuries before that. Stinchcomb
but are often quite toxic. Ernst et al. describe an et al. show that river hydrology was modified
alternative approach to interfere with the ubiq- by, and so records, this history as well. They
uitin proteasome (UPS) pathway. A highly active focused on the Delaware River Valley, where
ubiquitin-specific protease domain was used to artifacts show widespread settlement from
remove ubiquitin preemptively from substrates about 1100 to 1600 CE, including expansion of
about to be destroyed, and so stabilize them. The maize agriculture and forest clearing. Carbon
technique allowed the uncoupling of dislocation isotope, radiocarbon dating, and phytolith
and degradation of endoplasmic reticulum–de- analyses document the increase in maize and
rived misfolded proteins. This approach efficiently other grasses. Analysis of sediments shows
and globally blocked the UPS pathway, but was increased sedimentation during this interval in
less cytotoxic than commonly used pharmacologi- stream valleys and also an increase in flooding.
cal inhibitors. — SMH Together, the data imply that perhaps half of
PLOS Biol. 8, e1000605 (2011). the surrounding forests were cleared in the lo-
cal floodplain. Flooding may have been further
NEUROSCIENCE augmented by cooler and wetter conditions
from 1450 to 1530 CE. Thus, pre-Columbian
Obesity’s Chicken or Egg agriculture and deforestation also left a
Altered reward circuitry in the brain may play marked sedimentary record, at least locally in
a role in obesity. One change that has been North America. — BH
observed is that overweight people have fewer Geology 39, 363 (2011).
dopamine D2 receptors in the brain striatum;
however, it is unclear whether this is a cause PHYSICS
or consequence of overeating. Stice et al. used
functional magnetic resonance imaging to look
Complex Quantum Simulation
at vulnerability to obesity by examining neural Interactions between the charge, spin, and
responses to food and related cues in high-risk orbital degrees of freedom of electrons in
though still-lean adolescents. They found that a condensed-matter systems can give rise to
corticostriatal network responded to food receipt, many complex electronic and magnetic phases.
but not to anticipation of food-related cues, more The narrow, or often fixed, range of vari-
strongly in these high-risk able materials parameters can
people. A related network be a limitation in probing and
in high-risk individuals understanding the evolution of
also responded more to the order parameters of such
the receipt of money. complex correlated systems. An
These people also showed array of atoms trapped in an
greater activation of optical lattice has the potential to
the oral regions of the be extremely flexible in terms of
somatosensory cortex in tuning the parameters. Although
response to palatable food the atoms tend to be isotropic,
intake, a result specific for leading to somewhat trivial
food rather than money. systems, much theoretical work
Thus, youths at risk for obesity initially had a has explored the possibilities of finding ways to
generally elevated reward region responsivity. imprint and detect more complicated order pa-
When coupled with an increased responsivity of rameters on the lattice of trapped atoms. It is
oral somatosensory regions, this may result in along such lines that Kitagawa et al. propose a
CREDIT: STICE ET AL., J. NEUROSCI. 31, 4360 (2011)

overeating that subsequently produces dopamine spectroscopic technique based on two-particle


receptor down-regulation and elevated incentive interferometry that probes the phase-sensitive
salience of food cues. — PRS correlations between atom-atom interactions
J. Neurosci. 31, 4360 (2011). across the lattice. They show that the technique
should allow the measurement of nontrivial or-
GEOLOGY der parameters in entangled ensembles of cold
atoms, such as d- or p-wave pairing of electrons
Records in the River found in exotic superconductors and superfluids,
The expansion of agriculture, mills, and and the realization of cold-atom systems that
deforestation after colonial settlement of function as complex quantum simulators. — ISO
eastern North America expanded erosion and Phys. Rev. Lett. 106, 115302 (2011).

WorldMags www.sciencemag.org SCIENCE VOL 332 1 APRIL 2011


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SENIOR EDITORIAL BOARD Robert H. Crabtree, Yale Univ. Peter Jonas, Universität Freiburg Barbara A. Romanowicz, Univ. of California, Berkeley
Wolfgang Cramer, Potsdam Inst. for Climate Impact Research Barbara B. Kahn, Harvard Medical School Jens Rostrup-Nielsen, Haldor Topsoe
Cori Bargmann, The Rockefeller Univ. F. Fleming Crim, Univ. of Wisconsin Daniel Kahne, Harvard Univ. Edward M. Rubin, Lawrence Berkeley National Lab
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BOARD OF REVIEWING EDITORS Claude Desplan, New York Univ. Lee Kump, Penn State Univ. Christine Seidman, Harvard Medical School
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Peter Andolfatto, Princeton Univ. Tim Elston, Univ. of North Carolina at Chapel Hill Jonathan Losos, Harvard Univ. Yoshiko Takahashi, Nara Inst. of Science and Technology
Meinrat O. Andreae, Max Planck Inst., Mainz Gerhard Ertl, Fritz-Haber-Institut, Berlin Ke Lu, Chinese Acad. of Sciences John Thomas, Duke Univ.
John A. Bargh, Yale Univ. Barry Everitt, Univ. of Cambridge Laura Machesky, CRUK Beatson Inst. for Cancer Research Jurg Tschopp, Univ. of Lausanne
Ben Barres, Stanford Medical School Paul G. Falkowski, Rutgers Univ. Andrew P. MacKenzie, Univ. of St Andrews Herbert Virgin, Washington Univ.
Marisa Bartolomei, Univ. of Penn. School of Med. Ernst Fehr, Univ. of Zurich Anne Magurran, Univ. of St Andrews Bert Vogelstein, Johns Hopkins Univ.
Jordi Bascompte, Estación Biológica de Doñana, CSIC Tom Fenchel, Univ. of Copenhagen Oscar Marin, CSIC & Univ. Miguel Hernández Cynthia Volkert, Univ. of Gottingen
Facundo Batista, London Research Inst. Alain Fischer, INSERM Charles Marshall, Univ. of California, Berkeley Bruce D. Walker, Harvard Medical School
Ray H. Baughman, Univ. of Texas, Dallas Wulfram Gerstner, EPFL Lausanne Martin M. Matzuk, Baylor College of Medicine Ian Walmsley, Univ. of Oxford
David Baum, Univ. of Wisconsin Karl-Heinz Glassmeier, Inst. for Geophysics & Grahma Medley, Univ. of Warwick Christopher A. Walsh, Harvard Medical School
Yasmine Belkaid, NIAID, NIH Extraterrestrial Physics Yasushi Miyashita, Univ. of Tokyo David A. Wardle, Swedish Univ. of Agric Sciences
Stephen J. Benkovic, Penn State Univ. Diane Griffin, Johns Hopkins Bloomberg School of Richard Morris, Univ. of Edinburgh Detlef Weigel, Max Planck Inst., Tübingen
Gregory C. Beroza, Stanford Univ. Public Health Edvard Moser, Norwegian Univ. of Science and Technology Jonathan Weissman, Univ. of California, San Francisco
Ton Bisseling, Wageningen Univ. Taekjip Ha, Univ. of Illinois at Urbana-Champaign Sean Munro, MRC Lab. of Molecular Biology Sue Wessler, Univ. of California, Riverside
Peer Bork, EMBL Christian Haass, Ludwig Maximilians Univ. Naoto Nagaosa, Univ. of Tokyo Ian A. Wilson, The Scripps Res. Inst.
Bernard Bourdon, Ecole Normale Superieure de Lyon Steven Hahn, Fred Hutchinson Cancer Research Center James Nelson, Stanford Univ. School of Med. Timothy D. Wilson, Univ. of Virginia
Ian Boyd, Univ. of St. Andrews Gregory J. Hannon, Cold Spring Harbor Lab. Timothy W. Nilsen, Case Western Reserve Univ. Jan Zaanen, Leiden Univ.
Robert W. Boyd, Univ. of Rochester Dennis L. Hartmann, Univ. of Washington Pär Nordlund, Karolinska Inst. Mayana Zatz, University of Sao Paolo
Paul M. Brakefield, Univ. of Cambridge Martin Heimann, Max Planck Inst., Jena Helga Nowotny, European Research Advisory Board Jonathan Zehr, Ocean Sciences
Christian Büchel, Universitätsklinikum Hamburg-Eppendorf James A. Hendler, Rensselaer Polytechnic Inst. Stuart H. Orkin, Dana-Farber Cancer Inst. Huda Zoghbi, Baylor College of Medicine
Joseph A. Burns, Cornell Univ. Janet G. Hering, Swiss Fed. Inst. of Aquatic Christine Ortiz, MIT Maria Zuber, MIT
William P. Butz, Population Reference Bureau Science & Technology Elinor Ostrom, Indiana Univ.
Gyorgy Buzsaki, Rutgers Univ. Ray Hilborn, Univ. of Washington Andrew Oswald, Univ. of Warwick
Mats Carlsson, Univ. of Oslo Michael E. Himmel, National Renewable Energy Lab. Jonathan T. Overpeck, Univ. of Arizona BOOK REVIEW BOARD
Mildred Cho, Stanford Univ. Kei Hirose, Tokyo Inst. of Technology P. David Pearson, Univ. of California, Berkeley John Aldrich, Duke Univ.
David Clapham, Children’s Hospital, Boston Ove Hoegh-Guldberg, Univ. of Queensland Reginald M. Penner, Univ. of California, Irvine David Bloom, Harvard Univ.
David Clary, Univ. of Oxford David Holden, Imperial College John H. J. Petrini, Memorial Sloan-Kettering Cancer Center Angela Creager, Princeton Univ.
J. M. Claverie, CNRS, Marseille Lora Hooper, UT Southwestern Medical Ctr at Dallas Simon Phillpot, Univ. of Florida Richard Shweder, Univ. of Chicago
Jonathan D. Cohen, Princeton Univ. Jeffrey A. Hubbell, EPFL Lausanne Philippe Poulin, CNRS Ed Wasserman, DuPont
Andrew Cossins, Univ. of Liverpool Steven Jacobsen, Univ. of California, Los Angeles Colin Renfrew, Univ. of Cambridge Lewis Wolpert, Univ. College London
Alan Cowman, Walter & Eliza Hall Inst. Kai Johnsson, Ecole Polytechnique Federale de Lausanne Trevor Robbins, Univ. of Cambridge

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NEWS OF THE WEEK

are this week sending three state-of-the-art


AROUND THE WORLD submersibles to scour the sea floor about
500 kilometers off Brazil’s northeast coast.
Three previous attempts to locate the
1 downed Airbus A 330 of Air France Flight
6 4 447, including last year’s by this same group
7 from the Woods Hole Oceanographic Institu-
tion (WHOI) in Massachusetts, have failed.
2 The team will spend more than 3 months
canvassing an area of 10,000 square kilo-
3
meters, the size of Delaware and Rhode
Island combined. Using sonar, each REMUS
6000 autonomous underwater vehicle (AUV)
5 can crudely image a swath of sea floor just
1.2 kilometers wide while skimming the bot-
tom at 5 kilometers per hour. But the AUVs
London 1 that were found in areas not covered dur- can operate simultaneously and indepen-
ing the last survey. However, tigers are now dently for up to 20 hours before returning to
Budget Boosts Science, Slightly squeezed into 72,000 square kilometers, a the mother ship to dump their data.
The United Kingdom’s budget for 2011–12, range that has shrunk 20,800 square kilo- Oceanographers must then identify
announced last week, has a modicum of meters in 5 years. what might be a crumpled or even dismem-
good news for scientists. Spending on capi- These numbers, released earlier this bered plane on the rocky, rugged bottom of
tal projects got a £100 million boost, soft- week by India’s environment minister Jairam the Mid-Atlantic Ridge and send an AUV
ening the cuts in last year’s comprehensive Ramesh, come from a massive 18-month, back to take close-up photographs. WHOI
spending review. In the life sciences, $2.1 million survey that involved 800 researchers are hopeful of success; they’ve
£44 million will go to the Babraham camera traps and 476,000 people walking been studying that ridge for 30 years.
Research Campus near Cambridge and 625,000 kilometers looking for scat and
£26 million will go to Norwich Research other signs of tigers. Mount Paektu, North Korean–Chinese Border 4
Park. In the physical sciences, £10 mil-
lion will fund new instruments for the ISIS
Two Koreas Explore
spallation neutron source at the Rutherford Volcanic Détente
Appleton Laboratory and a further £10 mil- Koreans cherish Mount Paektu on the North
lion will support the development of next- Korean–Chinese border as the birthplace of
generation particle accelerators for medical their nation. Now the venerated volcano has
and security scanning applications at the inspired a rare attempt at scientific partner-
Daresbury Laboratory. Yet another £10 mil- ship on the divided peninsula.
lion will fund a new National Space Tech- About 1000 years ago, Mount Paektu
nology Program. disgorged up to 30 cubic kilometers of
The budget also creates a new health magma—10 times as much as Krakatoa did
research regulatory agency to streamline in 1883. Smaller eruptions have occurred
regulation and improve the cost effective- roughly every century since, until 1903.
ness of clinical trials. Imran Khan, director Mount Paektu’s plumbing rumbled anew
of the Campaign for Science and Engineer- several years ago, but the volcano did not
ing, welcomed the new money, but warned One expert called the results “very
that “labs across the country are going to be encouraging,” but P. K. Sen, former direc-
struggling to make ends meet.” tor of the government-sponsored conserva- NOTED
http://scim.ag/uk-budget tion initiative Project Tiger, called the new > If your favorite American college
figures “statistical jugglery.” “The habitat basketball team is in a slump, try the
India 2 of the tiger has only shrunk, poaching has “Tweet 16.” Cornell University’s Lab
increased, and conservation has been diluted, of Ornithology has launched its own
Tiger Numbers Up? Maybe so how can the numbers of tigers increase?” March Migration Madness, a Facebook
India is boasting about a 12% increase in he says. http://scim.ag/tiger-survey popularity tournament featuring North
the country’s adult tiger population, but American birds (http://scim.ag/tweet-
some tiger experts think the numbers don’t South Atlantic Ocean 3 16). The bald eagle, beloved of Ameri-
CREDIT: PALLAVA BAGLA

add up. India today accounts for almost cans, was left out: “We didn’t want any-
60% of the world’s wild tigers. A 2006 sur-
Once Again Into the Depths one to be conflicted about voting for or
vey estimated that the country housed 1165 In a determined effort to retrieve the flight against our national symbol,” the lab’s
to 1657 tigers. The latest survey counts recorders from a doomed 2009 flight, ocean- Web site says.
1571 to 1875 tigers, including 100 tigers ographers working with French authorities

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18 1 APRIL 2011 VOL 332 SCIENCE www.sciencemag.org
NEWS
Brussels 6 THEY SAID IT
Europe Nudges Top Scientists “Now I know why they went
to Market extinct! Nature abhors a
Some of Europe’s top scientists will get vacuum.”
financial help to take their discoveries to the
marketplace. The European Research Coun- —Kirt, one of our online readers, who
cil (ERC), the European Union’s funding commented on a story about plant-eating
program for frontier research, will offer sci- sauropod dinosaurs and their improbably
Mount Paektu’s caldera. entists it already funds the chance to apply long necks. To find out “How a Dinosaur Is
for €150,000 “Proof of Concept” grants. Like a Vacuum Cleaner,” see p. 21.
Researchers can use the funds to clarify
erupt, and since 2005 it has been largely intellectual property questions, do market
quiet (Science, 30 July 2010, p. 498). research, and team up with venture capital- is there, someone [from industry] will pick
A few days after the Tohoku earthquake ists, according to a 25 March announcement. up on it.”
struck Japan on 11 March, North Korea’s The idea grew out of the ERC Scientific Peter Tindemans, a Dutch physicist and
earthquake bureau floated the idea of a Council’s efforts to build better relations E.U. science policy expert, welcomed the
North-South project on Mount Paektu’s with industry, says ERC President and new grants. “The combination of the ERC
hazards. As a result, at a highly symbolic Scientific Council Chair Helga Nowotny. focusing on very high scientific originality
29 March meeting at the border village of Although ERC grants are open to company and quality—and stimulating people to think
Munsan, three scientists with North Korea’s scientists, “We have very, very few apply,” about what it might mean for society? I think
Institute of Paektu-san Volcano and four she says. “Hopefully, where the potential it’s a very good development,” he says.
South Korean counterparts agreed to begin
work on a joint research agenda.

Johannesburg, South Africa 5


End to Partnership With
Israeli University
The faculty senate of the University of
Johannesburg in South Africa voted last
week to terminate a collaborative research
agreement on water pollution studies with
its 25-year research partner, the Ben Gurion
University of the Negev (BGU) in Be’er
Sheva, Israel. Proponents of an international
academic campaign to sever ties with Israeli
researchers hailed the step as a “boycott.”
But University of Johannesburg Vice Chan-
CREDITS (TOP T BOTTOM): © IMAGINECHINA/CORBIS; © THE JANE GOODALL INSTITUTE (2)

cellor and Principal Ihron Rensberg rejected


the term, saying “peer-to-peer” collabora-
tions could continue.
A petition circulated by pro-boycott
supporters before the vote refers to BGU’s
“complicity in Israeli apartheid”—its failure
to involve Palestinians in research projects—
and “its direct and deliberate collaboration Durham, North Carolina 7
with the Israeli Defense Force,” a reference
Trove of Vintage Primate Data Goes Digital
to BGU’s scholarships for military person-
nel. About 400 South African academics Jane Goodall had no scientific training when she arrived in Tanzania in July 1960 to begin
endorsed the petition. studying chimps, but the then 26-year-old was meticulous about recording the behavior,
The Jerusalem Post reported that BGU habits, and even personalities of her primate subjects. This week, Goodall gave a lecture
issued a statement calling the petition “a at Duke University to mark the beginning of a new life for the 50 years of data collection
collection of lies and mistruths about BGU that followed. Led by Anne Pusey, an evolutionary anthropologist who has been working
and the State of Israel,” adding that “it with Goodall for 41 years, Duke scientists are digitizing 20 file cabinets’ worth of hand-
would be unfortunate to cancel a research written notes, typed audio transcriptions, and color-coded check sheets (see inset) that
agreement that is meant solely to improve comprise the complete life histories of more than 200 chimpanzees. Pusey hopes the
the quality of life for the residents of South effort, dubbed the Jane Goodall Institute Research Center, will open up the data to new
Africa.” http://scim.ag/SA-Israel generations of scientists.

WorldMags www.sciencemag.org SCIENCE VOL 332 1 APRIL 2011 19


NEWS OF THE WEEK

NEWSMAKERS For Milnor, the it seems impossibly hard, but then you just
prize caps a long put together an idea here and an idea there,
and distinguished and somehow the answer just drops out.”
career. In 1956, http://scim.ag/abel-prize
he produced what
others immedi-
ately recognized as
Bug Expert Snags Enviro Prize
a masterpiece for For more than 35 years, May Berenbaum
the ages: a seven- has been a champion of insects, studying
dimensional sphere how they interact with plants and humans
too badly twisted to be unscrambled with- and conveying her fascination with bugs to
out creating corners and folds. By the rules the general public. For this work, the Uni-
of topology, two spaces are considered versity of Illinois, Urbana-Champaign, ento-
equivalent if one can be bent, stretched, mologist will receive the 2011 Tyler Prize
and perhaps folded until it looks like the for Environmental Achievement.
Trailblazer of other. Creases are not allowed. Before Mil- Berenbaum helped elucidate the molec-
nor, no one knew that this restriction made ular arms race between plants trying to
Chemical Ecology Dies any difference; for spaces of three dimen- fend off herbivores and insects that evolve
Thomas Eisner, an ecologist and evolution- sions or fewer, it does not. His insight has ways to sidestep, and sometimes make use
ary biologist at Cornell University, died last led to decades of research in mathematics of, these defenses. Ever since she was an
week at age 81 of complications from Par- and physics. undergraduate, she has reached out to the

CREDITS (TOP TO BOTTOM): MARCO MARTENS; ROBERT BARKER/CORNELL UNIVERSITY PHOTOGRAPHY; THOMAS EISNER/AAAS (INSET); GETTY IMAGES/STOCKBYTE PLATINUM
kinson’s disease. Milnor says that what he loves most general public. “I serve as a self-appointed
In hundreds of journal articles on topics about mathematics is “a feeling of miracles.” spokesperson for all things six-legged,” she
ranging from spider webs to bombardier bee- He adds, “You’re working on a problem and says. In 2006, she led a National Research
tles, Eisner explored how insects and arthro-
pods defend themselves, capture prey, and
attract mates in sometimes complex ways.
With Cornell collaborator Jerrold Meinwald,
he helped found the field of chemical ecol-
ogy—the study of how animals and plants
use chemicals to communicate. An outspo-
ken conservationist, Eisner promoted the
idea of allowing companies to “bioprospect”
in the rainforest for useful chemicals in order
to raise money to protect biodiversity.
Eisner was also a pianist, a popular sci-
ence writer, and—with his wife, Maria—a
nature photographer whose images of larval
hooks (pictured), beetle hairs, and other min-
ute wonders graced many pages and covers
of Science. “He was a remarkable, amaz-
ingly accomplished individual who met every
challenge with courage and grace and good
humor. He was my personal scientific
hero,” says University of Illinois, Urbana-
Champaign, entomologist May Berenbaum, Grown on Garbage
who earned her doctorate at Cornell.
Piles of garbage left by humans thousands of years ago in the Florida Everglades may have
helped the formation of tree islands like this one, according to a new study.
Pioneer of High-Dimensional
Previously, scientists had presumed that the larger tree islands, which host two to three
Spaces Wins Abel Prize times the number of species living in the surrounding marsh, formed atop topographical
The 2011 Abel Prize in mathematics goes high spots in underlying carbonate bedrock. But during their fieldwork, Gail Chmura and
to John Milnor, a topologist and dynamical Maria-Theresia Graf, both paleoecologists at McGill University in Montreal, Canada, found
systems theorist at Stony Brook University instead concretelike layers of carbonate formed by water’s evaporation from the peaty soil.
in New York state. Worth approximately Beneath the layers were prehistoric trash heaps, or middens.
$1 million and first awarded by the Nor- Slightly higher and drier than the surrounding marsh, the middens could have offered
wegian Academy of Science and Letters in a foothold for trees, shrubs, and other vegetation, the pair reported last week at a meeting
2003, the prize has acquired a nearly Nobel- of the American Geophysical Union in Santa Fe. Bones in the trash would have been a good
level cachet among mathematicians. source of phosphorus, a scarce nutrient in the Everglades. http://scim.ag/tree-island

WorldMags
20 1 APRIL 2011 VOL 332 SCIENCE www.sciencemag.org
NEWS
Council panel that pointed out the precari- Random Sample
ous state of pollinators in the United States.
Later, her work on bee colony collapsing
disorder helped focus attention on viral
Friendly Fires
causes of this epidemic. Just after sunset on Saturday, 19 March, archaeologist
She hopes to use the $200,000 prize to Erin Robinson waited with a small crowd of volunteers
promote citizen science, possibly by expand- at Moel y Gaer, an Iron Age hill fort in Wales not far
ing a local Illinois bee spotting program that from the English border. They were watching another
involves the general public in bee surveys. “I hill fort, Moel Fenlli, about 10 km to the southwest,
dream of taking it national,” she says. waiting for a flare to shoot up. “There was just a huge
http://scim.ag/enviro-prize bolt of excitement when it went off,” Robinson says.
“We had a huge cheer.”
A view from a Welsh hill fort.
The volunteers were part of an experiment to see
Three Q’s whether the people who occupied hill forts along the
BEIJING—Last Welsh-English border some 2500 years ago could have seen each other and maybe even sent
month, physical signals with fire. After the flare’s signal, the group on Moel y Gaer shone their flashlights at the
chemist Bai Chunli people at Moel Fenlli, who flashed theirs back, simulating light from a fire. Over the next hour,
was appointed presi- the greeting was repeated among a total of 10 hill forts.
dent of the Chinese Robinson’s doctoral research at Bangor University in Wales is on the connections between
Academy of Sciences the different hill forts, such as shared architectural styles. If these sites were occupied at the
(CAS), China’s top same time, they would have been aware of each other, the experiment shows. “The thing that
research body with I found more than anything was the emotional attachment,” Robinson says. “By seeing people
tens of thousands of scientists at dozens of with a signaling light on a fellow hill fort, maybe up to 40 kilometers away, you felt the sense
institutes across the nation (see http://scim. that you were part of one large community.”
ag/cas-pres). Science spoke with Bai about
innovation, which China, like Europe and
the United States, emphasizes as a crucial FINDINGS would require 50% of the animal’s entire
driver of future economic growth. energy stores. The paper shows a long
How a Dinosaur Is Like neck’s advantage on the ground, he con-
Q: What are the obstacles to China’s a Vacuum Cleaner tends. “Let’s just leave it there and not ask
innovation efforts? the sauropods to raise their necks.”
Previously, China had hoped that by ced- The plant-eating sauropod dinosaurs, such http://scim.ag/long-necks
ing market shares to foreign companies, we as Brachiosaurus and Apatosaurus (for-
could in exchange obtain advanced technol- merly called Brontosaurus), were the larg-
ogy and increase our capacity for innovation. est animals ever, weighing up to 80 metric
Test Tells If the Heart Fits
However, we have realized that core tech- tons and stretching up to 30 meters in length. Every year, about 4000 people world-
nologies could not be obtained this way, nor Many also sported very long necks—though wide get a heart transplant; roughly 40%
could they be purchased. Technologies that researchers have debated their purpose. Now, of them experience at least one episode of
are truly essential [to our economy] must be two scientists in the United Kingdom may acute organ rejection within a year. Usu-
developed indigenously. finally have the answer. ally patients must undergo regular biopsies
Evolutionary ecologists Graeme Ruxton of their new organ to monitor its health. The
CREDITS (TOP TO BOTTOM): GETTY IMAGES; CHINESE ACADEMY OF SCIENCES (CAS)

Q: What is your vision for CAS’s “Innova- of the University of Glasgow and David procedure is both painful and expensive, but
tion 2020” project, which sets priority R&D Wilkinson of Liverpool John Moores Uni- now a new blood test could help.
areas for the next decade? versity created a simplified mathematical Biophysicist Stephen Quake and his col-
The main goal is to solve science and tech- model of Brachiosaurus. By varying the leagues at Stanford University developed
nology problems that are of strategic impor- dinosaur’s dimensions, the duo found that its a test that monitors fragments of DNA that
tance to China’s modernization and mean- 9-meter neck gave Brachiosaurus an 80% are released into the bloodstream when cells
while to develop CAS into a world-class energy savings in foraging compared with from the transplant tissue are broken down.
research institution. The central govern- a 6-meter-long-neck. Like a clunky, old- When a transplant goes well, donor organ
ment’s investment will emphasize stable sup- fashioned vacuum cleaner with a long tube, DNA typically makes up 1% of free DNA
port for talents on the one hand, and mega- Brachiosaurus could graze widely without in the recipient’s blood. During a rejection
projects and infrastructure development on having to move its huge body. The energy event, that fraction increases to an average
the other. savings might even have allowed the dino- of 3%, the team reports online this week in
saur to browse the treetops, the pair suggest the Proceedings of National Academy of
Q: How will CAS increase its ability in a paper published online 23 March in Sciences. Researchers hope that this test can
to innovate? Biology Letters. eliminate the need for regular biopsies as a
We will center around three ideas: more Not so fast, says physiologist Roger means of rejection monitoring. The new test
democracy, more openness, and [giving] Seymour of the University of Adelaide in is likely to be available to doctors in a year’s
more prominence to talent. Australia: Pumping blood to a raised head time. http://scim.ag/organ-test

WorldMags www.sciencemag.org SCIENCE VOL 332 1 APRIL 2011 21


NEWS & ANALYSIS

1990s, “many people didn’t believe tsuna-


mis left deposits,” says Joanne Bourgeois, a
tsunami geologist at the University of Wash-
ington, Seattle. Minoura was among the
paleotsunami pioneers when he started dig-
ging in the Sendai Plain. Recent sediment sur-
veys have supported his Jogan findings, while
studies of accumulating crustal strain in the
Sendai area hinted at the possibility of a major
earthquake. Even so, before the 11 March
quake some scientists “did not believe” the
region was primed for a big earthquake, says
Yuichiro Tanioka, a seismologist at Hokkaido
University in Sapporo.
Planners and engineers began to recog-
Over the top. The 11 March tsunami nize the significance of geologic research for
overwhelmed a coastal seawall earthquake preparedness in the late 1970s,
in Miyako City designed for after paleoseismic studies revealed the reg-
lesser waves. ular recurrence of earthquakes along the
San Andreas fault in California. But paleo
studies didn’t directly influence public pol-
J A PA N D I S A S T E R icy until the mid-1990s. An early example
is the Cascadia earthquake, now known to

Scientific Consensus on have occurred in the subduction zone off


North America’s Pacific Coast in 1700. In
1986, researchers reported the first geologi-

Great Quake Came Too Late cal evidence for this massive event: a sudden
drop in elevation of coastal regions, inferred
from sedimentary deposits, a sign of slip-
TOKYO—Ten years ago, Koji Minoura, a “It’s necessary to communicate research page on the upper side of a subduction zone.
geologist at Tohoku University in Sendai, findings to society,” says Yukinobu Okamura, Eight years later, a revision to the Uniform
and colleagues injected some science into a geologist at the Active Fault and Earthquake Building Code required buildings in west-
a legendary disaster. A historical document Research Center in Tsukuba, who led studies ern Washington and Oregon to be 50% more
compiled in 901 C.E. told of an earthquake that independently bolstered Minoura’s find- earthquake-resistant. Then in 1995, partly
in 869 C.E. that destroyed a castle town in ings. “We tried to do that in this case, but we because of the Pacific threat, the U.S. Con-
northeastern Japan and a subsequent tsunami weren’t in time.” gress passed the National Tsunami Hazard
that inundated the surrounding area, kill- One lesson is that incorporating geolog- Mitigation Program, which supports studies
ing 1000. Digging in rice paddies in what is ical studies of ancient earthquakes and tsu- of tsunami risk and emergency planning.
now called the Sendai Plain, Minoura’s team namis into risk assessments “is essential to The size and timing of the Cascadia earth-
found telltale marine sediments showing compensate for the limitations in the cur- quake were unclear. Those pieces of the puz-
that the tsunami ran as much as 4 kilometers rent evaluation scheme,” says Fumihiko zle turned up in Japan, where Kenji Satake,
inland. They estimated the Jogan earthquake’s Imamura, a tsunami engineer at Tohoku Uni- a seismologist now at University of Tokyo,
magnitude at 8.3 and concluded that it could versity in Sendai. and colleagues found Japanese accounts of a
recur at 1000-year intervals. “The possibility The need to revise earthquake probabil- tsunami without an apparent local cause. In
of a large tsunami striking the Sendai Plain is ity analyses extends far beyond Japan. “There Nature in 1996, they pinpointed the date of
high,” they wrote in a 2001 article in the Jour- are other subduction zones, near Java and the Cascadia earthquake as 26 January 1700
nal of Natural Disaster Science. New Zealand, where people think there is no and estimated a magnitude of 9.0. “There is a
That obscure paper is now at the center chance of a big quake” because they cling to lot of respect for [Japan’s] record-keeping dili-
of a growing debate about how quickly sci- old models of seismic processes, says Robert gence,” says Brian Atwater, a U.S. Geological
entific findings can and should influence McCaffrey, a geophysicist at Portland State Survey geologist at the University of Wash-
disaster-mitigation policies. A few years University in Oregon. But forecasts are gen- ington, Seattle.
before the magnitude-9.0 Tohoku earthquake erally based on studies covering the past sev- Japan’s Headquarters for Earthquake
struck northeastern Japan on 11 March, a eral centuries—“not long enough for the cycle Research Promotion produces seismic hazard
scientific consensus had begun to coalesce time for these big earthquakes,” he says. maps for the nation; they are used to estimate
around the idea that a Jogan-like event could Although scientists have been interrogat- potential tsunamis. The headquarters incor-
CREDIT: REUTERS

happen again. But that consensus did not ing geologic deposits for clues to the size and porates paleoseismic studies in determin-
influence seismic risk assessments, tsunami frequency of major earthquakes for several ing earthquake risk—but only in Hokkaido,
preparedness, or a review of the hardiness of decades, efforts to apply such techniques to Tanioka says. Hokkaido was the last region of
the Fukushima Daiichi nuclear power plant. ancient tsunamis are more recent. In the early modern Japan settled by ethnic Japanese, and

WorldMags
22 1 APRIL 2011 VOL 332 SCIENCE www.sciencemag.org
NEWS
reliable records go back only to the mid-1800s, earthquake occurred before the evaluation concerned mostly about earthquake shaking,
he says. Elsewhere, the agency relies on “doc- was completed,” he says. brushed aside his concerns, he asserts.
uments allowing the estimation of earthquake Any upward revision is now also too late Japan and other countries will surely
frequency and scale [going] back 400 years,” for the Fukushima plant. The first reactor was rethink tsunami threats—just as Minoura
Imamura says. Using those records, the earth- completed in 1971, long before the Jogan intends to do. Originally, he says, he tried
quake research headquarters warned that the event appeared on the scientific radar. Plan- to “simply make clear the geological pro-
area hit by the 11 March temblor faced a 99% ners girded for a maximum 5.7-meter tsu- cess of coastal environments.” But now, “I
probability of a magnitude-7.5 earthquake nami; Tokyo Electric Power Co. estimates that want to meditate deeply on the future of geo-
occurring in the next 30 years. the tsunami that took out the backup diesel logical work [related to] tsunamis,” he says.
Okamura and colleagues conducted more generators was 14 meters high. The company The Tohoku temblor should convince the
extensive surveys in the Sendai area in the missed a chance to address the deficiency scientific community and authorities that
mid-2000s that bolstered Minoura’s original when an expert panel reviewed the plant’s magnitude-9 earthquakes can occur anywhere
findings. According to Okamura, the earth- seismic resistance in 2008. As The Washing- along subduction zones, McCaffrey says.
quake research headquarters was studying ton Post reported, Okamura told the panel Like a tsunami, the effects of the 11 March
whether and how to include Jogan in its risk about the Jogan earthquake and warned that Tohoku earthquake will spread far and wide.
assessment for the Tohoku region. “But the a bigger tsunami was possible. The panel, –DENNIS NORMILE

A R C H A E O LO G Y

In Indus Times, the River Didn’t Run Through It


SANTA FE—The Saraswati was the mother of ologist Rita Wright of New York University in
all the holy rivers of India, flowing between New York City, who heard the presentations.
the Ganges and the Indus and dispensing “We may have to give up the idea of the Indus
milk and ghee before it dried up, according as a civilization based on rivers.”
to ancient Hindu scripture. Archaeologists To determine when the Ghaggar-Hakra
and some devout Hindus have long tried last was an active river, researchers looked
to pinpoint its course, which the scripture for the youngest sediments deposited CATION
LO
puts between the Indus and Ganges rivers. by flowing water. Each of the three
For more than a century the best candidate groups dated sediments primarily
has been the ancient channels of the now- with optically stimulated lumines-
dry Ghaggar-Hakra system in today’s India cence, a technique that uses the
and Pakistan. Along its course are scat- light energy stored in quartz grains
tered settlements of the Indus civilization, to estimate when the grains were AFGHANISTAN

us
which some Hindus see as the progenitor of last exposed to light. Gupta’s team
their traditions. drilled several 40-meter cores near the Ind
j
At a meeting* here last week, however, Indus city of Kalibangan, in today’s India, and PAKISTAN Sutle
three independent teams offered prelimi- found that river sediment deposits ceased after

Gan
Ghaggar-Hakra
nary evidence that the Ghaggar-Hakra was approximately 14,000 B.C.E., long before the

ges
at most a modest seasonal stream during and Indus culture. Gupta said in his talk that the Ara
us

bia INDIA
Ind

after the Indus flourished from 2500 B.C.E. to river may have jumped into the bed of the nS
ea
CREDITS (TOP TO BOTTOM): RAJIV SINHA / IIT-KANPUR; M. TWOMBLY/SCIENCE

1900 B.C.E. “We need more cores, but the Sutlej River to the west at this time. Hideaki
data suggests there was no big river here” in Maemoku of Hiroshima University led a Jap-
Indus times, said geologist Sanjeev Gupta of anese team that found that sand dunes sur- Dry hole. Researchers drill a core (top) in the bed of
Imperial College London in his talk. rounding the Ghaggar-Hakra are older than the ancient Ghaggar-Hakra River in India.
The findings puzzle and intrigue archae- 10,000 years, another indication any river
ologists. The Indus settlements along the present had long since dried up by that point. Clift says the drying of the Ghaggar-
Ghaggar-Hakra appear to have migrated over Maemoku’s poster gave this summation of the Hakra may reflect a drought that may yet help
time toward the river’s source. That has been would-be Saraswati: “No, it wasn’t mighty.” explain the civilization’s mysterious decline.
interpreted by some as a sign of decreasing Based on work downstream in Pakistan, However, other researchers note, even though
river flow and stress on the Indus society. If, another team, led by geologist Peter Clift no surface water flows today, the ancient
however, the river was dry or only seasonal, of the University of Aberdeen in the United channels still provide groundwater for farm-
it may prompt a re-evaluation of how Indus Kingdom, agrees that little water flowed regu- ers and might have done so in the past. And a
peoples acquired water for agriculture. “This larly in the system after 2500 B.C.E. But Clift dried-up riverbed may have been a safer place
is enormously important work,” says archae- believes the river may have simply shifted to to settle than the banks of a major river such as
*
another as-yet-unidentified channel and that the Indus, which flooded disastrously in 2010.
American Geophysical Union meeting, “Climates, Past
Landscapes and Civilizations,” 21–25 March 2011, there still may have been flow in the Ghaggar- “Now we have more questions,” Wright says.
Santa Fe. Hakra during Indus times. –ANDREW LAWLER

WorldMags www.sciencemag.org SCIENCE VOL 332 1 APRIL 2011 23


NEWS&ANALYSIS

doors, which allow fuel to pass underwater


from the reactor into the pool, are held shut by
rubber gaskets inflated by electric pumps. In
1986, at the Hatch nuclear plant near Baxley,
Georgia, the water level in a spent fuel pool
dropped by more than a meter after the seals
were left uninflated. But engineers say that
the channel between the reactor and the pool
is filled with water during maintenance peri-
ods, meaning that a leak would lengthen the
time it took to empty the pool. “It’s surprising
to me [that] the fuel became uncovered that
quickly,” says Lake Barrett, a retired nuclear
engineer and former U.S. Nuclear Regulatory
Commission (NRC) official.
J A PA N D I S A S T E R Determining the temperature of the pool
has been another challenge. (It was reported
Pool at Stricken Reactor #4 Holds to be 84˚C the day before the explosion;
no data have been subsequently released.)
Answers to Key Safety Questions Knowing that temperatures were high
enough to drive water completely from the
pool could help researchers quantify how
much radioactivity was released in sub-
Of all the terrible news from the crippled Hot fuel sequent steps. The day after the 15 March
Fukushima Daiichi nuclear power plant, The nuclear fuel at reactor #4 is made up of explosion, NRC Chair Gregory Jaczko said
reports about the spent fuel storage pool for uranium pellets held in 4-meter-long tubes that the pool had run dry at one point, a claim
reactor #4 may be among the most discon- made of zirconium alloy. The pool holds that the Japanese government has disputed.
certing for scientists. The pool held the entire 1331 bundles of tubes, known as assemblies; At least one fire in the pool—and pos-
complement of fuel rods from the reactor’s 548 were removed from the reactor in Janu- sibly a second—was reported by power
core, which had been emptied 3 months ary during maintenance. company officials after the explosion. Lab
before the 11 March earthquake and tsu- Daiichi has seven spent nuclear fuel experiments have shown that zirconium
nami struck. And yet on 15 March the build- pools: one for each of its six reactors, and can burn either with steam or with oxygen.
ing exploded, apparently fueled by hydro- a central one. They serve two main pur- Both reactions progress rapidly at roughly
gen, leaving nuclear engineers to speculate poses: to cool the fuel, which gives off heat 800˚C; the former, crucially, releases hydro-
about the source. Adding to the confusion as a result of radioactive decay, and to shield gen. The hydrogen explosion at reactor #4
are reports of fires in the pool, a worst-case workers and the environment from radiation. points to the steam reaction, which releases
scenario that had never before occurred in a In reactors with Fukushima Daiichi’s design, less energy and therefore melts the fuel
working nuclear plant. pools are not in sealed containment vessels more slowly. But knowing which reaction
Unraveling the mysteries surrounding the but are open and accessible; operators are dominated could help scientists quantify
#4 pool will require discovering why water keenly aware of the importance of keeping how much radioactivity was released from
levels there fell so quickly, and whether the water levels high. (Although the pool at reac- pool #4. A 2006 study by the U.S. National
230 tons of spent nuclear fuel melted in tor #3 may also have produced hydrogen, Research Council said that a heat up after
addition to catching on fire. Researchers the other five pools have required constant a loss-of-water event could melt the spent
also need to quantify how much radioac- replenishment but remained stable.) fuel, allowing the escape of volatile radio-
tive material might have been released. The One mystery about the #4 pool is how nuclides, including “a substantial fraction of
events at the #4 pool could shed light on the its water level fell so quickly. During nor- the cesium,” into the air.
dangers posed by spent fuel in pools at more mal operation, 7 meters of roughly 40˚C Soil samples analyzed by the Japanese sci-
than 350 reactors globally, and what needs to water sit between the top of the fuel rods ence ministry last week found cesium levels
be done to assure the public that they can be and the surface of the 1425-ton pool. The roughly equivalent to 8 million becquerels
operated safely. water is constantly circulated and replen- per square meter near the plant. That level, if
As Science went to press, extremely high ished.There’s little doubt that temperatures accurate, would be higher than those found
levels of radiation were hampering efforts in the pool would have risen steadily after near Chernobyl. (Radioactive iodine has been
to restore power and water lines to all six power was lost. But several scientists have found in Japanese tap water, but its 8-day half-
reactors at the complex. And while a pos- independently calculated that it would take life means that it couldn’t have come from the
sibly damaged core in reactor #3 was leak- much longer than 4 days—perhaps as much older spent fuel in pool #4. Reactor #3 may be
ing highly radioactive water, reactor #4’s as 3 weeks—for the heat of the fresh fuel in the source.) Scientists also don’t know what
pool remains among the biggest potential the #4 pool to evaporate or boil off the water. fraction of the radioactive cesium released is
CREDIT: REUTERS

sources of radiation. In video released early Could the #4 pool’s structure have been from reactors or from spent fuel. Scientists
this week, what appeared to be steam con- damaged in the quake or subsequent explo- hope more detailed isotopic measurements
tinued to billow from reactor #4’s blown-out sions or both? Among possible weak points will shed light on the age and, therefore, the
frame despite continued efforts to add water. are the large doors on the side of the pool. The source of the radioactive particles.

WorldMags
24 1 APRIL 2011 VOL 332 SCIENCE www.sciencemag.org
NEWS&ANALYSIS

Minding the pools REACTOR #4: THE SECRETS OF A SPENT FUEL POOL
Some experts believe that governments and
the nuclear power industry have done a poor What caused the loss of water in the pool, and
job of sharing information on the risk of zir- how low did the water level get?
Whether the water drained, evaporated, or boiled off
conium fires. Critics of NRC say that studies would provide key clues.
conducted for the agency likely contain rele-
vant data but have been kept classified to keep What caused the hydrogen explosion?
Zirconium alloy, which makes up the tubes holding the
the information away from terrorists. “To the uranium fuel pellets, reacts with steam to form hydrogen,
extent that any experiments have been done at which can ignite in the presence of oxygen.
all, the public doesn’t know about them,” says
spent-fuel expert Gordon Thompson of Clark What temperature was the water?
The zirconium reaction progresses at temperatures above
University in Worcester, Massachusetts. The 800˚C.
National Research Council study called on
NRC to “improve the sharing of pertinent What do recorded levels of cesium-137 outside
information” on pool risks. the plant mean?
Melted and aerosolized long-lived radionuclides suggest
The calamity at Fukushima Daiichi has a hot fire in the pool.
raised particular concerns about U.S. spent
nuclear fuel pools, which are thought to be
packed more tightly than those in Europe now mixes hot, fresh spent fuel with older highly unlikely to catch fire. Still, the indus-
or Asia. “Spent nuclear fuel may be more fuel in the pools to redistribute the heat. But try has begun a safety review of U.S. reac-
vulnerable than we thought,” says Edwin it balked at a 2008 recommendation by Jac- tors, and NRC has launched two studies into
Lyman of the Union of Concerned Scientists zko—speaking in an unofficial capacity—to U.S. plant safety that could lead to new rules
in Washington, D.C. The nuclear industry transfer U.S. fuel older than 5 years to dry on spent fuel. –ELI KINTISCH
has added additional sprayers to pools and concrete casks, where the cooled fuel is With reporting by Dennis Normile in Tokyo.

C H E M I ST RY

Artificial Leaf Turns Sunlight Into a Cheap Energy Source


ANAHEIM, CALIFORNIA— Nearly all the Three years ago, an MIT team led by environment than existing H2-generating
energy we use on this planet starts out as chemist Daniel Nocera devised a special compounds typically face.
sunlight that plants use to knit chemical cobalt and phosphorus-based catalyst that To make its artificial leaf, the MIT team
bonds. Now, for the first time, researchers breaks water molecules apart and knits pairs spread its catalysts on opposite sides of a
at the Massachusetts Institute of Technol- of oxygen atoms into O2 molecules (Science, silicon wafer. The silicon absorbs sunlight
ogy (MIT) have created a potentially cheap, 1 August 2008, p. 620). Researchers had pre- and passes energetic, negatively charged
practical artificial leaf that does much the viously made H2-forming catalysts. But these electrons and positively charged electron
same thing. vacancies to the catalysts on opposite sides
The new device is a silicon wafer about that use them to make H2 and O2. When the
the shape and size of a playing card. Dif- device is placed in a clear jar and exposed
ferent catalysts coat each side of the wafer. to sunlight, the setup converts 5.5% of the
The silicon absorbs sunlight and passes that energy in sunlight into hydrogen fuel. “You
energy to the catalysts to split water into literally walk outside, hold it up, and it
molecules of hydrogen (H 2) and oxygen works,” Nocera says.
(O2). Hydrogen is a fuel that can be either Nocera says he hopes to commercial-
burned or used in a fuel cell to create elec- ize the new technology within 2 to 3 years.
CREDITS (TOP TO BOTTOM): M. TWOMBLY/SCIENCE; ISTOCKPHOTO

tricity, reforming water in either case. This Later this year, a company he founded, Sun
means that, in theory, anyone with access to Catalytix, expects to produce a prototype
water can use it to create a cheap, clean, and electrolyzer using the cobalt catalyst and an
available source of fuel. The splits. A new silicon wafer can make hydrogen external electricity source to split water to
“It’s spectacular,” says Robert Grubbs, a fuel from sunlight and water. generate hydrogen. Sunlight-to-fuel water
chemist at the California Institute of Technol- splitters using both new catalysts will likely
ogy in Pasadena, who saw the presentation were expensive. Earlier this week, Nocera follow after that, he says. In addition, Nocera
here last weekend at the biannual meeting reported devising a cheap catalyst that uses is teaming up with Ratan Tata, chair of Tata
of the American Chemical Society. “There’s three different metals to form H2. Group, an Indian conglomerate, in hopes of
still obviously a long way to go” to make the Nocera didn’t reveal the makeup of the producing a refrigerator-sized power plant
new device into a rugged, real-world technol- new catalyst, as the work is not yet published, capable of converting sunlight and water
ogy, Grubbs says. But the approach is impor- and he is in the process of patenting it. But into electricity. The goal is cheap, renewable
tant because its potential low cost could he notes that finding his new H2-forming power for vast numbers of people lacking
make it widely available. It “has a chance of catalyst was made easier by the fact that his access to large amounts of energy.
being scalable,” Grubbs says. O2 catalyst works in water, a more benign –ROBERT F. SERVICE

WorldMags www.sciencemag.org SCIENCE VOL 332 1 APRIL 2011 25


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A N T H R A X I N V E S T I G AT I O N

Army Missed Warning Signs About Alleged Anthrax Mailer


A new report detailing the mental health evidence in support of the DOJ’s finding.” USAMRIID has declined to comment
problems of U.S. Army researcher Bruce Drawing upon 3 decades of mental health on the panel’s findings. However, Depart-
Ivins, the alleged perpetrator of the 2001 records, the panel—chaired by Gregory ment of Defense officials have stated in the
anthrax attacks, blames the U.S. Army Medi- Saathoff, a psychiatrist at the University of past that the Ivins affair has led to enhanced
cal Research Institute of Infectious Diseases Virginia, Charlottesville—describes Ivins as background checks and stricter monitoring
(USAMRIID) for not scrutinizing Ivins’s a deeply disturbed individual who projected a of all personnel working with dangerous
background adequately before hiring him and “benign eccentricity” that “masked his obses- pathogens and toxins. Those new proce-
providing him with the security clearances sions and criminal thoughts.” After being dures, which have been in place since 2008,
that allowed him to work with anthrax at the rejected by a woman from the Kappa Kappa include psychological evaluations and peri-
institute in Frederick, Maryland. The report Gamma sorority during his undergraduate odic drug tests.
says that if USAMRIID managers had looked days at the University of Cincinnati, Ivins Whether the same standards of screen-
at Ivins’s psychiatric records, which they had developed a lifelong obsession with KKG, ing and monitoring will eventually be
the authority to access, they would have spot- applied to biodefense labs in academia and
ted behavioral red flags that would have auto- industry remains an open question. Aca-
matically disqualified him from working in a demic researchers who work with any of
biocontainment suite. The report’s findings the 82 pathogens and toxins on the so-called
have rekindled a debate over how funding select-agent list currently undergo a basic
agencies, institutions, and labs should screen background check limited to screening the
and monitor researchers with access to dan- applicant’s name against a set of criminal
gerous pathogens. and terrorist databases. Last year, the White
Ivins, who worked at USAMRIID for House announced an initiative to overhaul
35 years, committed suicide on 29 July the entire security framework for research
2008 as federal investigators were preparing involving select agents: under this plan, the
to go public with the charges against him. government will rank select agents by risk
The Department of Justice (DOJ) has since and apply tougher security measures for
released thousands of pages of investiga- those in the top tier.
tive material supporting its conclusion that Biodefense researchers are opposed to
Ivins was the killer. That material included tougher screening and monitoring proce-
scientific evidence linking the anthrax in the dures. Microbiologist David Relman of Stan-
letters to a flask of spores under Ivins’s con- ford University in Palo Alto, California, a
trol and other evidence such as the scientist’s member of the National Science Advisory
long nighttime stays at his lab in the months Board for Biosecurity (NSABB), says that
before the attacks. But former colleagues Troubled. Ivins juggled at parties and volunteered some testing might be counterproductive
of Ivins’s and many others have challenged for the Red Cross but was also plagued by strange because “it may lull us into a sense of secu-
the government’s conclusion. And a recent obsessions and criminal thoughts, says a new report. rity and wrongfully impugn creative, eccen-
review by a panel of the National Research tric, but harmless individuals.” NSABB has
Council found that the scientific evidence breaking into the sorority’s buildings several recommended that institutions enhance bio-
isn’t as ironclad as claimed by federal offi- times. The mailbox where the anthrax letters security by encouraging scientists to report
cials (Science, 18 February, p. 835). were mailed is situated within 200 feet of a suspicious behaviors of lab mates.
By contrast, the latest report—written KKG office at Princeton University. Richard Ebright, a biologist at Rut-
by a panel of nine experts from fields such The report says Ivins’s mental health issues gers University in New Brunswick, New
as psychiatry, medicine, and organizational stemmed in part from a traumatic childhood Jersey, does not believe in NSABB’s self-
systems—unambiguously endorses the gov- during which his mother stabbed and beat his governance model, noting that the new report
ernment’s implication of Ivins. The report father, his mother physically abused Ivins, suggests that well-meaning colleagues and
was ordered in September 2009 by Chief and his father mocked him publicly. Over supervisors are unlikely to be a good defense
Judge Royce Lamberth of the U.S. Dis- the years, Ivins revealed his criminal behav- against an insider threat. “It is absolutely clear
trict Court in Washington, D.C., after DOJ iors and obsessions selectively to mental that the 2001 anthrax attacks would not have
requested a study of Ivins’s sealed psychi- health professionals; in the 1990s, a therapist occurred if any one of three security measures
atric records. The panel’s findings were sub- became so alarmed that she made tentative had been implemented,” Ebright says, citing
mitted to the court on 23 August 2010 and inquiries with the local police department. video monitoring of biocontainment areas, a
released publicly last week. “Dr. Ivins was Yet, when filling out medical forms with his two-person rule requiring that nobody work
psychologically disposed to undertake the employer, Ivins omitted critical information alone in a biocontainment facility, as Ivins
mailings; his behavioral history demon- to conceal his history of behavioral problems. did, and psychological background checks.
strated his potential for carrying them out; The report faults USAMRIID for not fol- The way to enhance biosecurity and prevent
and he had the motivation and the means,” lowing up on these discrepancies in Ivins’s another insider attack, he says, is for the gov-
CREDIT: AP

the report concludes. “The psychiatric paperwork, which would have brought his ernment to mandate each of those measures.
records offer considerable circumstantial psychiatric problems to light. –YUDHIJIT BHATTACHARJEE

WorldMags www.sciencemag.org SCIENCE VOL 332 1 APRIL 2011 27


NEWSFOCUS

The Rise of
Animal Law
Will growing interest in how the legal system
deals with animals ultimately lead to changes
for researchers?
AT THE OREGON NATIONAL PRIMATE RESEARCH CENTER IN
Beaverton, some 20 law students tour the outdoor enclosures that
house breeding colonies of macaque and rhesus monkeys and talk
with the veterinarian in charge of their care. “It’s a very powerful trip
for the students,” says Kathy Hessler, who teaches a course on animal
law at Lewis & Clark Law School in nearby Portland. “Some of them
are really shaken.” That’s not because they see violations of the law,
Hessler explains: “The primate center is working very hard to meet the
requirements under the law, but there’s a disconnect between what the
law provides and what the students think the animals need.”
Hessler and her class are part of the rapidly growing field of animal
law, a relatively new area of study that examines—and often challenges—
how the law treats animals. As recently as 2000, only a handful of law
schools in the United States offered courses in animal law. Now roughly
120 do. These include several of the nation’s premier law schools, includ-
ing Harvard, Stanford, and Columbia, which have established endowed pro-
grams in animal law thanks to $1 million donations from TV celebrity and
longtime animal rights activist Bob Barker (see table). Some of those who
teach animal law courses, including Hessler, describe themselves as activists.
Others shy away from that label. But many take issue with a legal sys-
tem that treats animals as property and provides few mechanisms for
protecting their interests in court.
Some of these legal scholars have proposed strategies for
advancing animal rights through steppingstone cases that erode the
notion of animals as property and grant them some of the same pro-
tections people have. Others, drawing inspiration from antislavery
and civil rights movements, advocate a more direct effort to establish
fundamental rights for animals—at least for more cognitively sophisti-
cated species such as great apes and cetaceans (see sidebar, p. 30). No one
is arguing that orangutans should be given the right to vote, but some legal scholars
see no reason why apes shouldn’t have rights similar to those of a child or a person in a
coma. Whether these efforts will succeed remains to be seen. But if they do, there could

CREDITS: (TOP LEFT PHOTO) TED S. WARREN/AP; (OTHER PHOTOS) THINKSTOCK


be repercussions for everyone who works with animals—including scientists.
“It’s a developing area of law, and we’re monitoring it closely to see how it may
evolve,” says Andrew Cardon, director of state and legal affairs for the National
Association for Biomedical Research, an advocacy group in Washington, D.C. “Our
concern is that incremental changes in the law could have negative consequences for
lifesaving research.”

A movement is born
Joyce Tischler has loved animals since she was a child. After graduating from law school in
1977, she began searching for a way to use her law degree to help animals. She and a like-
minded colleague put an ad in a San Francisco legal newspaper to see whether anyone else
shared their interests. “About six people showed up to our first meeting,” Tischler says. “We
formed a little group and met for several years to educate ourselves about the laws that relate to
animals.” That group grew into the Animal Legal Defense Fund (ALDF), a Cotati, California,
organization that has been a driving force in the growth of animal law.
ALDF’s efforts include litigation, legislation, and education. The group has filed scores
of civil lawsuits to protect animals and assists with hundreds of criminal prosecutions each

WorldMags
28 11 APRIL
APRIL 2011
2011 VOL
VOL 332
332 SCIENCE
SCIENCE www.sciencemag.org
www.sciencemag.org
NEWSFOCUS

CALIFORNIA MISSOURI WASHINGTON, D.C. BOLIVIA


In 2008, voters passed a Voters passed a ballot The U.S. Supreme Court In 2009, it became the first
ballot measure to prohibit measure in 2010 intended overturned a federal ban in country to ban the use of
extreme confinement of to prevent inhumane 2010 on "crush videos" animals in circuses.
certain farm animals. It is treatment at large-scale showing graphic violence
expected to become law
by 2015.
puppy breeders. Last
month the state senate
against animals.
Animal Planet
overturned it. A selection of notable international animal protection laws
1 2 3 4
6 7

5 8
2 3
1

5 6 7 8 9
SPAIN SWITZERLAND AUSTRIA CHINA NEW ZEALAND
It became the first country In 2009, its Supreme Court It banned research on apes The country's first anti- In 2000, it became the first
to acknowledge rights upheld a ban on neuro- in 2006. In 2008, its cruelty law, drafted in country to ban most uses 9
for great apes with a 2009 science experiments on Supreme Court declined to 2009, would provide of great apes for research,
law granting rights to life, macaques. In 2010, voters acknowledge personhood protections for pets as testing, and teaching.
liberty, and freedom rejected a plan to appoint for a chimpanzee, re- well as animals used in
from torture. state-funded lawyers to buffing activists hoping to agriculture, entertainment,
represent abused animals. gain guardianship of a and research. It has yet to
chimp at a struggling be enacted.
animal shelter.

year. In 2010, ALDF and other animal pro- tice Section in 2004. The committee sponsors viduals and considered part of the family
tection groups successfully sued to stop continuing education courses for practicing circle,” says David Favre, a leading animal
BP from carrying out “controlled burns” lawyers and develops policy proposals aimed law scholar who teaches at Michigan State
of spilled oil in the Gulf of Mexico that at improving animal welfare. The Association University College of Law in East Lansing.
would have endangered sea turtles. ALDF of American Law Schools started a section on People’s bonds with their pets tend to fos-
drafted a 2008 Virginia law that toughened animal law in 2008 to promote education and ter protective attitudes toward other ani-
penalties for dogfighting in the wake of the professional development. mals, Favre says. That’s reflected in a spate
Michael Vick scandal. (Vick, an Ameri- Tischler and other animal law pioneers of recent state laws that punish not only ani-
can football star, was convicted in 2007 on attribute the field’s rapid growth to a com- mal cruelty but also neglect. Fourteen states
dogfighting charges.) Tischler says she’s bination of societal change and scientific now have laws that explicitly prohibit leav-
especially excited about a current proj- advances in animal cognition. “Pets are ing animals in an unattended vehicle in hot
ect in which ALDF lawyers are working becoming of increasing importance to indi- or cold weather, for example.
with scientists and leaders from govern-
ment and industry on strategies for imple-
menting a 2007 National Research Council The Price Is Right: $1 Million. As the game show’s host for 35 years, Bob Barker gradually
report urging companies to adopt alterna- eliminated fur and leather prizes and signed off each episode with a plea for viewers to spay and neuter their pets.
More recently, he’s written $1 million checks to eight leading law schools to endow programs in animal rights law,
tives to toxicity testing in animals. ALDF’s
plus two to his alma mater, Drury University in Springfield, Missouri, for undergraduate animal rights studies.
Web site encourages visitors to petition
CREDIT (BOTTOM): GENE BLEVINS/LA DAILY NEWS/CORBIS

Congress to adopt an Animal Bill of Rights,


which includes “The right of laboratory ani- YEAR SCHOOL
mals not to be used in cruel or unnecessary 2001 Harvard Law School
experiments.” 2004 Duke University School of Law
ALDF now has student chapters at 155 2004 Stanford Law School
of the 200 U.S. law schools accredited by the 2004 Columbia Law School
American Bar Association (ABA). ALDF 2004 UCLA School of Law
student chapters help establish animal law 2005 Northwestern University School of Law
courses, arrange talks and symposia, and pro- 2006 Georgetown University Law Center
duce articles for law review journals. 2008 Drury University (undergraduate)
Mainstream legal establishments are tak- 2009 University of Virginia School of Law
ing notice. ABA created a committee on ani- 2009 Drury University (undergraduate)
mal law under its Tort Trial and Insurance Prac-

WorldMags www.sciencemag.org SCIENCE VOL 332 1 APRIL 2011 29


NEWSFOCUS

At the same time, books such as The According to animal law scholars and ing potentially precedent-setting cases. One
Omnivore’s Dilemma and movies such as practitioners, the law has not kept up with sci- of the most active areas involves monetary
Food, Inc. have increased public concern ence and society. “The legal and even moral awards for emotional distress suffered by pet
about how animals are raised and slaugh- distinctions we make about how we treat [ani- owners, says Bruce Wagman, a lawyer who
tered for food, and the law is changing in this mals] are based on the choices humans make teaches at the University of California (UC)
arena, too. In 2008, for example, California about using animals and have nothing to do Hastings College of the Law in San Fran-
voters approved a ballot measure that will with the scientifically determined capacity of cisco and developed the first casebook on
outlaw cages that restrict the movement of animals to feel pain or be self-aware or any animal law. “That’s a hotbed of litigation and
egg-laying hens, calves raised for veal, and of those things,” Hessler says. A pet rat, a judicial opinions,” Wagman says.
pregnant sows (see map, p. 29). lab rat, an endangered wild rat, and a city rat Historically, in cases in which a pet has
In parallel with these societal changes, that gnaws its way into someone’s basement been killed, U.S. courts have limited awards
research with a wide range of nonhu- all have a similar interest in staying alive and to the purchase price or replacement cost of
man animals has demonstrated behaviors avoiding pain, Hessler says, but the law now the animal—typically a few hundred dollars.
and traits once thought to be the exclusive treats them very differently. “Inclusion of the In recent years, grieving pet owners have
domain of humans, including cooperation, interests of the animals themselves is what is argued that emotional bonds with pets are
altruism, empathy, and a sense of fairness. novel in the animal law approach,” she says. comparable to those with family, and they’ve
“Science is incredibly important to animal sought monetary compensation for emo-
law,” says Mariann Sullivan, a New York Case studies tional distress. Courts often award damages
City lawyer who chairs the ABA’s Animal Some students may take animal law courses for emotional distress after the death of an
Law Committee. “Cognitive ethology is because they’re already interested in animal immediate family member, but not for loss
really what animal lawyers rely on in argu- protection, but instructors say many more of property, Wagman says. Pet owners have
ing that conditions for animals in any area sign up simply because the field is new and had some success when the pet’s death was
should be improved.” fast-moving. Coursework includes study- caused intentionally. In 2006, for example,

A Road Map for Animal Rights In law review articles and books, Wise has laid out a philosophical
framework for animal rights. He argues that some nonhuman animals,
In 1772, a slave named James Somerset won his freedom in an English court. particularly great apes and cetaceans, are cognitively complex in many of
Months earlier, three people acting on his behalf applied to the Court of the same ways that humans are: They can have desires, act intentionally,
King’s Bench for a writ of habeas corpus, which would require Somerset’s and have some sense of self. Therefore, Wise asserts, they deserve basic
captor—he’d escaped his owner and been recaptured—to bring Somerset “dignity” rights, such as the right not to be harmed or held in a distress-
before the court to determine the legality of his imprisonment. In deciding ing environment. Human infants and people in a vegetative state have
that English common law provided no basis for holding Somerset, the court such rights, and Wise argues that a chimpanzee of similar or greater intel-
brought an end to slavery in that country. ligence should be granted them as well.
The case is a potential blueprint for establishing personhood and legal Getting a judge or jury to consider these arguments is the goal of NHRP.
rights for animals, says Steven Wise, a lawyer and legal scholar in Coral Since 2007, Wise has recruited more than 50 volunteers, including law-
Gables, Florida, and founder of the Nonhuman yers and sociologists, who are working to iden-
Rights Project (NHRP). In the eyes of the law, ani- tify potential plaintiffs and determine which
mals are considered things to be owned, as slaves jurisdictions are most likely to be sympathetic
once were, Wise notes: “The story of James Som- to their arguments and which legal strategies
erset is a metaphor for how any legal thing [such are most likely to be effective. He estimates that
as an animal] can use the court system to become they’ve spent a cumulative 20,000 hours ana-
a legal person.” lyzing dozens of legal and sociological issues in
That’s a goal Wise has been working toward all 50 states.
for 30 years, and he now says his group is close The first case will likely involve an animal
to filing lawsuits on behalf of intelligent animals being held in substandard conditions: perhaps a
such as chimpanzees and dolphins in an attempt dolphin kept in a small pool at an aquarium or a
to convince courts that at least some nonhuman chimpanzee confined to a small cage at a zoo or
animals meet the requirements of legal person- research facility. NHRP will file a lawsuit in trial
hood and should be accorded certain basic rights. court, probably using habeas corpus or another
“We’re hoping to file the first suits, if everything common law writ, de homine replegiando, used
goes right, in 2012, and if everything goes wrong, centuries ago in slavery cases.
in 2013,” Wise says. If the trial court dismisses the case, Wise
As improbable as it may sound, there’s a says he will appeal all the way to the state’s
chance he will succeed, says Richard Cupp, a highest court. NHRP is combing over the judi-
CREDIT: ASSOCIATED PRESS

legal scholar at Pepperdine University in Malibu, cial decisions of state appellate court and high
California. “Steven is a very smart guy, and he’ll Rattling cages. Steven Wise wants court judges to determine their judicial philos-
choose his jurisdictions very carefully,” Cupp says. courts to acknowledge “dignity” ophies. Volunteers are also looking for courts
“In the short term, I suspect he won’t be success- rights for some animals. sympathetic to civil rights and animal welfare
ful, but I could be wrong.” issues, as well as those that have ruled in favor

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30 1 APRIL 2011 VOL 332 SCIENCE www.sciencemag.org
NEWSFOCUS

a Washington state judge awarded a woman Such cases erode the notion of animals as gation and lobbying efforts at HSUS involve
$5000 for emotional distress after a boy stole property and move them closer toward some pets, livestock, and wildlife, but the group
her cat from her porch and took it to a nearby of the protections and privileges accorded to also takes on issues involving research ani-
schoolyard, where he doused it in gasoline people—a move that concerns some advo- mals when the opportunity arises, including
and set it on fire. However, when a pet dies cates of biomedical research. But Favre, pushing for the Great Ape Protection Act,
as a result of negligence—due to veterinary whose writings on animal law and philoso- which would ban invasive research on those
malpractice, for example—few if any courts phy are required reading in many animal law animals (Science, 13 March 2009, p. 1414).
have been willing to award damages for emo- courses, finds it long overdue. In a 2010 arti- Some research advocates are wary of all
tional distress, Wagman says: “That’s the cle in the Marquette Law Review, he argues these trends. “Those of us who represent sci-
dividing line now, but people are constantly for classifying domestic animals as “living entists who work with animals don’t look on
trying to push that envelope.” property.” This designation would acknowl- this as a positive development, although a
The law is also changing rapidly in how edge that animals have interests—in stay- lot of what they’re doing we have no objec-
animals are dealt with in the establishment ing alive, moving freely about, and socializ- tion to,” says Deborah Runkle, a senior pro-
of trusts and custody cases. Forty-five states ing with other members of their species, for gram associate at the American Association
have statutes enabling people to set up trusts example—that should be weighed against for the Advancement of Science, which sup-
to provide for their pets after their death, up human interests by the legal system. ports the use of animals in scientific research
from eight states in 2000. Pets are increas- Favre argues that the law already provides (and publishes Science). “It’s not an imme-
ingly an issue in divorce proceedings, too, modest rights for animals to protect these diate threat, but it’s something that needs to
with judges being forced to decide whether interests: Anticruelty laws protect their right be watched,” says Alice Ra’anan, director
to treat pets as property, whereby whoever not to be harmed, for instance. He advocates of government relations and science policy
bought the animal keeps it, or more like chil- expanding such existing rights and creat- for the American Physiological Society. “If
dren, for whom consideration is given to who ing new ones. Perhaps most provocatively, there’s a concern, it’s that there are relatively
can provide the best home. he argues in a 2005 article in the Michigan few lawyers who are interested in this who
State Law Review that animals, through self- have an understanding and appreciation of
appointed attorneys, should have the right to animal research and of the laws that already
of gay marriage, which Wise suspects might sue humans who violate their primary inter- exist to protect animals.”
reflect a sensitivity to equality that would work ests. Currently, animals do not have legal The growth of animal law both reflects
in his favor. standing to sue, and animal welfare advo- and encourages societal change, says Richard
People have tried previously—and unsuc- cates have had limited success suing on Cupp, who writes and teaches about the legal
cessfully—to gain legal standing for animals. their behalf. That’s because courts will only and moral standing of animals at Pepperdine
In 1998, Wise lost a case in which he argued consider harm done to a human being, leav- University School of Law in Malibu, Califor-
that a dolphin named Kama had legal stand- ing animal advocates in the difficult posi- nia. Cupp applauds legal protections for ani-
ing to sue the New England Aquarium to pre- tion of arguing that they themselves have mal welfare, but in several law review articles
vent being transferred to a Navy marine mam- been harmed by an animal’s suffering. Favre he has argued that establishing legal rights for
mal facility. In 2004, a district judge in San argues that an animal’s interests should be animals would not serve society’s best inter-
Francisco ruled that whales, porpoises, and part of the legal equation. ests. To pick one example, if animals were
dolphins (represented by a self-appointed given the right to sue as Favre proposes, activ-
attorney) did not have legal standing under Reason for concern? ists suing on behalf of research animals could
federal law to sue the Navy to stop alleg- Although the growth of animal law is unde- bog down universities with endless lawsuits.
edly harmful sonar testing. In both cases, niable, the implications for animal research “We could lose a lot of research that might be
the judges ruled that only “persons” can sue are uncertain. There are serious barriers very helpful,” Cupp says.
under federal law and that the legislators who to implementing the kind of theoretical At a more philosophical level, Cupp
wrote the laws did not intend the definition of changes to the legal system that Favre and argues that talking about rights for animals
“person” to include cetaceans. others advocate, says Taimie Bryant, who obscures the fact that at the end of the day any
Wise says he’s learned from his mistakes teaches animal law at the UC Los Angeles legal case involving animals will be decided
in the Kama case. That’s why he’s focusing on School of Law. “How you would take that by humans. The developing field of animal
state common law. “Common law is the law that from academia and put it into a practical set- law should focus on emphasizing and delin-
judges make, so you don’t get into this issue ting where most entities that use animals eating humans’ moral responsibility toward
of legislative intent,” he says. “We’re looking have more lobbying power than academics other animals rather than on establishing legal
for courts that view common law as elastic, as isn’t clear,” Bryant says. She thinks changes rights, Cupp says: “We’re stepping toward
something that changes as morality changes or that affect scientists are more likely to come something, and the fight is over what we
as new scientific facts come in” about the cogni- from societal change and the efforts of orga- should be stepping toward.” –GREG MILLER
tive capabilities of nonhuman animals. nizations like the ALDF and the Humane
If he wins, the animal in question will be Society of the United States (HSUS). Read more about animal law cases and issues
moved to a better home. But more impor- Indeed, the HSUS legal team has grown online:
tant from Wise’s perspective, a legal door that from three full-time lawyers in 2005 to 16 Animal Legal Defense Fund: http://www.aldf.org/
has been slammed shut will have opened just today, and the organization draws from a net-
a crack, enabling him and others to push for work of 2000 lawyers who have volunteered Animal Legal and Historical Center at Michigan State
University College of Law: http://www.animallaw.info/
more rights for more animals. “Win or lose, to work pro bono, says Jonathan Lovvorn,
we’re going to keep going,” he says. –G.M. vice president and chief counsel of animal National Association for Biomedical Research, Animal
protection litigation and research. Most liti- Law Section: http://www.nabranimallaw.org/

WorldMags www.sciencemag.org SCIENCE VOL 332 1 APRIL 2011 31


NEWSFOCUS

He has started to investigate


this theory by giving mice either
low doses of antibiotics over long
periods, akin to what farm ani-
mals receive, or short-term, high
doses, more like what a sick infant
or adult would get. He then com-
pares the physiology and microbi-
omes of these treated rodents with
those of mice raised under similar
conditions but given no antibiot-
ics. In one set of studies, the mice
fed low doses of antibiotics long-
M I C R O B I O LO G Y term wound up with 15% more
body fat than the control mice,
Girth and the Gut (Bacteria) Blaser reported last month at the
International Human Microbiome
Mouse, human studies begin to clarify gut bacteria’s role in obesity Congress in Vancouver, Canada.
The chubbier, antibiotic-fed mice
also had about 25% more fat in
their livers.
Five years ago, a team headed by Jeffrey versity of Maryland School of Medicine in The treated mice also had a different set
Gordon of Washington University in St. Baltimore who has studied gut bacteria and of bacterial species inhabiting their guts.
Louis (WUSTL) in Missouri made a surpris- obesity in the Amish. And several hundred bacterial genes, includ-
ing discovery: The guts of obese mice and ing ones for fatty acid production, exhibited
people harbor an array of microbes different Case of the missing microbes different levels of activity—some increas-
from that of their lean counterparts. More The farm animal–antibiotic connection ing, others decreasing—in these mice com-
provocatively, when they gave lean mice was one clue that led Blaser to wonder pared with the controls. Similar changes
certain gut-dwelling microbes, the rodents about microbial causes of the obesity epi- occur in the rodents given short pulses of
became fat (Science, 29 May 2009, p. 1136). demic. Another was the fact that very few antibiotics, he noted.
The findings sparked headlines and fueled people now harbor the ulcer-causing bacte- Antibiotics “may be driving the gut
popular speculation that manipulating gut rium Helicobacter pylori in their stomachs. microbiome to a place where it shouldn’t
bacteria might keep weight down in people. H. pylori, which has also been linked to be,” Fraser-Liggett says. “We do not know
Already, Martin Blaser had been head- stomach cancers, is one of up to 1000 differ- the functional consequences, but with these
ing down a similar track. Blaser, a microbi- ent microbes that call the human body home. miracle drugs now 60 years later, we may be
ologist at New York University in New York Once ubiquitous in the human microbiome seeing effects that change susceptibility to
City, was struck by how successful farmers and still so in the guts of people from devel- various diseases.”
are at increasing the growth rates of livestock oping countries, it is now found in just 6% Blaser will examine the gut microbiomes
by adding low doses of antibiotics to their of U.S. children. That might seem like good of children to see whether his results are
feed. “The earlier in life they start the antibi- news, as there should be fewer ulcers and applicable to humans. If so, “that would be a
otic, the more profound the effect,” he points cancers. But Blaser suspects that it is also remarkable connection that could have a sig-
out. He began to wonder whether antibiotic bad news, as studies suggest that H. pylori’s nificant impact on medical care,” says genome
use, particularly in children, might affect the presence in the gut helps regulate the stom- scientist George Weinstock of WUSTL. But
long-term establishment of a balanced micro- ach’s production of the hormone ghrelin, he’s cautious: “In a lot of cases, the micro-
bial community in the human gut, eliminat- which stimulates food intake. biome in mice doesn’t translate into humans.”
ing bacteria there that could help ward off This bacterium may
CREDITS (TOP TO BOTTOM): RADE LUKOVIC/THINKSTOCK; JASON HE
obesity. He started conducting mouse studies not be the only species Patterns in genes
to examine the hypothesis. disappearing from our S. Dusko Ehrlich has
Since then, several other groups have microbiome. After a avoided that issue,
joined in. A raft of intriguing obesity- person takes antibiotics, bypassing mice and
related findings was presented at a meeting “it has always been pre- instead directly exam-
last month on the microbiome, the bacteria sumed that the micro- ining whether patterns
that live inside the guts and other tissues of biota will spring back,” in the microbiome of
animals. Yet many in the field caution that Blaser says. But the fate people relate to body
it remains difficult to determine whether of H. pylori suggests mass index and obesity.
changes in gut microbes drive or contribute otherwise. Its vanishing A microbiologist at the
to obesity or whether the excess weight itself act and other shifts in the INRA Microbiology
triggers those changes. “The jury is still out microbiome may con- and Food Chain Divi-
[about] what the role of the gut microbiota tribute to an increased Go with the gut. Antibiotic use may sion in Jouy-en-Josas,
may be in obesity in humans,” says Claire risk for weight gain, adversely affect the long-term makeup of France, Ehrlich is part
Fraser-Liggett, a microbiologist at the Uni- Blaser worries. the intestine’s bacterial communities. of a group, the Meta-

WorldMags
32 1 APRIL 2011 VOL 332 SCIENCE www.sciencemag.org
NEWSFOCUS

HIT consortium, investigating connections of obesity, notes Ehrlich. “If we can provide rial genes are active in a person and not just at
between microbial genes in human intestines evidence that they [at least] provide a contri- which bacteria are there. Scientists have found
and human health. By comparing such genes bution, then we can go and find a treatment.” that although the species mix of the micro-
from obese and nonobese individuals, he and biome may vary significantly from one person
his colleagues have found that certain sets of Help from the Amish to the next, those individuals often still have
bacterial genes and bacteria correlate with Other work presented at the microbiome equivalent complements of bacterial genes at
excess weight and insulin resistance. meeting indicates that sorting out this cause- work inside them. Through such gene analy-
The researchers first sequenced all the bac- and-effect puzzle will be tough. Frustrated by ses, researchers can begin to better assess
terial genes in stool samples of 177 Danes, 55 the inconsistent results others were getting what the bacteria in the gut are really doing to,
who were thin and 122 who were either over- when they looked for connections between the or for, their host, Fraser-Liggett notes.
weight or obese. Although the researchers microbiome and obesity, Fraser-Liggett and Gordon suggests that more clarity on the
concluded that most participants in the study her colleagues examined 400 adult Amish liv- obesity-microbiome issue will also come
had roughly 600,000 distinct bacterial genes ing in Pennsylvania. Amish marry within their from using the guts of mice as bioreactors
in their guts, almost one-third of the obese group and have very similar lifestyles, envi- for human microbes. His group has pio-
study participants had only about 360,000 ronment, and eating habits—they even cook neered the study of germ-free mice, which
such genes, 30% to 40% fewer. A similar per- in communal kitchens. Thus, Fraser-Liggett are grown in a sterile environment from
centage of 36 obese French people had a com- hoped to eliminate some of the variables that birth, and he is now exposing such mice
parable dearth of gut bacteria genes, Ehrlich might have confounded other studies. to bacteria from human guts. Once those
reported at the Vancouver meeting. Moreover, The body mass index of Amish ranged human microbes have established residence
the obese people “don’t have as great a bac- from 16 to 51 (30 is obese), and some of the in the guts of the mice, Gordon then feeds
terial diversity” in their the animals a variety of
guts, Ehrlich reported. One human diets. Using these
missing microbe in that rodent proxies, he can
group was a methane pro- thus track how different
ducer, leading Ehrlich to diets affect the “human”
wonder whether “the car- microbiomes, assessing
bon that does not get out the bacteria as often as he
[of the body] as gas could needs to to get a dynamic
be incorporated as fat.” picture. “You can sample
When they looked many features between the
at medical histories of microbial community and
all their study subjects, the host,” he says.
Ehrlich and his colleagues Despite his role in ignit-
found that the obese peo- ing the study of obesity
ple with fewer gut bacte- Personalized microbiota. and microbiomes, Gordon
ria genes were more likely Germ-free mice grown in resists the idea that our gut
to be insulin resistant than sterile environments and bacteria are the sole expla-
were the obese people given human gut microbes nation for the growing
who had a typical tally of provide a way to test links number of obese people.
intestinal microbial genes. between bacteria and obesity. “It’s not the dominant part
These obese people also of the problem; excessive
tended to have higher than energy intake is,” he con-
normal white blood cell counts, suggesting obese ones also had metabolic syndrome. tends. The simplistic notion of only chang-
that they were in a state of low-level inflam- Fraser-Liggett and her colleagues captured ing one’s gut bacteria to lose weight has been
CREDIT: LAURA KYRO/CENTER FOR GENOME SCIENCES & SYSTEMS BIOLOGY

mation, Ehrlich said. Some researchers have a snapshot of the gut microbiome of each “hyped a lot,” he complains.
found evidence of a link between inflam- Amish by obtaining stool samples, sequenc- Others, such as microbial ecologist Lip-
mation and obesity (Science, 17 December ing the DNA in them, and using the 16S ribo- ing Zhao of Shanghai Jiao Tong University
2010, p. 1621). somal subunit gene often used to tell bacteria in China, are more convinced that the micro-
Ehrlich and his colleagues have also tested apart, identifying any microbial components. biome will prove important when it comes
whether the types of bacteria in a person’s gut Although the scientists did detect some dif- to obesity. “Increased abundance of ‘bad
can “diagnose” obesity. Using just six meta- ferences in certain bacteria between obese genes’ and [a] decrease of ‘good genes’ in
species, they were able to correctly predict and lean Amish, they didn’t find the dramatic our diet-disrupted gut microbiome [may]
whether a person was lean or obese more than shifts that Gordon had documented between be the primary driving force for this obesity
80% of the time, he reported. When research- lean and obese mice, Fraser-Liggett reported epidemic,” Zhao says.
ers try to make the same predictions by con- at the meeting. Even if Zhao’s prediction proves right,
sidering all of a person’s genetic risk factors One problem may be that simply taking a the studies to date make clear that the con-
for obesity, they are right only 58% of the census of the bacteria present in a person’s gut nection between the microbiome and excess
time, Ehrlich pointed out. may not be enough. “16S [analysis] is not very weight is complex, Fraser-Liggett says. For
At this point, however, it’s unclear whether informative,” Ehrlich says. “We need to go to those looking to bacteria to stem the obesity
the differences in intestinal microbes are “the more precise measures.” Increasingly, micro- epidemic, she concludes, “there’s clearly no
cause, a contribution to, or the consequence” biome researchers are looking at what bacte- magic formula.” –ELIZABETH PENNISI

WorldMags www.sciencemag.org SCIENCE VOL 332 1 APRIL 2011 33


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Dr. Carl
Dr. Carl Alving
Alving
on his
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inspiration
for inventing
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the vaccine patch.
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Chief of the Department of Adjuvant & Antigen Research,
Division of Retrovirology
at the Walter Reed Army Institute of Research
AAAS member

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WorldMags
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COMMENTARY
A balance of signals Fighting fungal infection

43 47
LETTERS I BOOKS I POLICY FORUM I EDUCATION FORUM I PERSPECTIVES

LETTERS
edited by Jennifer Sills

Protecting Invaders for Profit selling the invasive hare (Lepus europaeus) by millions to Europe (4).
In Patagonia, many farmers hunt or poison native guanacos (Lama
HUMANS HAVE SPREAD SPECIES TO NONNATIVE ENVIRONMENTS FOR guanicoe) to avoid competition with nonnative livestock or red deer.
generations. In turn, these species can become invasive, threatening Some nonnative species are even advertised as “typical” in the coun-
native species. There has been much discussion about the best way to tries where they are introduced. As a result, the citizens of southern
control invasive species and protect native species (1). However, one South America do not consider invasive species a problem (5).
point has been overlooked: In some cases, human commercial activity It is impractical to eradicate some invasive species. However, by
values invasive species more than valuing them more than native species, we are promoting their expan-
the native species, and danger- sion and endangering the native species. The discussion about inva-
ous behavior ensues. For example, sive species must focus on the prevention of their social and com-
trout (e.g., Salvelinus sp.) and red mercial overvaluation. We must also educate both local communities
deer (Cervus elaphus) were intro- and governments about the importance of maintaining and recovering
duced to Argentina and Chile from native species populations. In the long run, the negative consequences
the United States and Europe about of species introductions are greater than their short-term commercial
100 years ago for fishing and hunt- benefits (6). SERGIO A. LAMBERTUCCI* AND KARINA L. SPEZIALE
ing purposes. Today, these species Ecotono Laboratory, INIBIOMA (Comahue National University-CONICET), Bariloche, Argentina.
are invasive, but they represent an
*To whom correspondence should be addressed. E-mail: slambertucci@comahue-conicet.
economic resource for tourism and gob.ar
sport (2, 3). Because of their com-
mercial value, the Argentinean Native species at risk. Farmers in References
1. D. M. Richardson, Ed., Fifty Years of Invasion Ecology: The Legacy of Charles Elton
and Chilean governments main- Patagonia hunt guanacos to protect (Wiley-Blackwell, Oxford, 2011).
tain healthy populations by set- nonnative deer. 2. M. A. Pascual et al., Front. Ecol. Environ. 7, 533 (2009).
ting restrictions on hunting and 3. T. Veblen et al., Conserv. Biol. 6, 71 (1992).
4. S. A. Lambertucci et al., Environ. Sci. Technol. 44, 7759 (2010).
fishing seasons and the number of fish allowed per day. Similarly, the 5. K. L. Speziale, S. A. Lambertucci, Nature 467, 153 (2010).
Argentinean government allows local people to profit by hunting and 6. D. Pimentel et al., Agr. Ecosyst. Environ. 84, 1 (2001).

Culturomics: Statistical two common traps. First, they assume that the period than another, it does not necessarily
total number of words published in English mean that there were more dinosaurs—it may
Traps Muddy the Data is a meaningful statistic. Although this fig- be that there was more mud.
ure seems impressive—and has tradition- ELISE E. MORSE-GAGNÉ
IN THEIR GENERALLY WORTHWHILE DISCUS- ally been used to validate English speakers’ Department of English, Tougaloo College, Tougaloo, MS
sion of developments in the English language belief that their language is exceptional [e.g., 39174, USA. E-mail: egagne@tougaloo.edu
(“Quantitative analysis of culture using mil- (1)]—it primarily reflects the large number Reference
CREDIT: MARY FRANCES HOWARD/WIKEMEDIA COMMONS

lions of digitized books,” Research Article, of English speakers and their relatively high 1. H. Bradley, The Making of English (MacMillan, London,
14 January, p. 176), J.-B. Michel et al. fall into per capita publication rates. The statistic has 1904; reprinted by Dover, New York, 2006), p. 78.

little to do with the number of words avail-


able to an individual English speaker. Second,
Letters to the Editor the authors claim that the English lexicon “is Culturomics: Periodicals
Letters (~300 words) discuss material published in
Science in the past 3 months or matters of gen-
enjoying a period of enormous growth” and Gauge Culture’s Pulse
that “the size of the language” has grown
eral interest. Letters are not acknowledged upon
receipt. Whether published in full or in part, Let-
“by over 70% during the past 50 years.” FROM THE PERSPECTIVE OF AN ARTIST
ters are subject to editing for clarity and space. However, they are not measuring the English who mines digital information to under-
Letters submitted, published, or posted elsewhere, lexicon directly; they are measuring the writ- stand shifts in temporal culture, the analy-
in print or online, will be disqualified. To submit a ten record of the English lexicon. These two sis of Google books and the initial descrip-
Letter, go to www.submit2science.org. concepts should be kept distinct. If the fossil tion of trends in our culture by J.-B. Michel
record shows more dinosaur footprints in one et al. (“Quantitative analysis of culture using

WorldMags www.sciencemag.org SCIENCE VOL 332 1 APRIL 2011 35


LETTERS

millions of digitized books,” Research Article, tic and points out that such measures are usu-
14 January, p. 176) is an important step for- ally associated with rather dubious attempts
ward in using current digital techniques as a to prove the superiority of the English lan-
window into history. Although Michel et al.’s guage. We share her concern. The concept of
study was rigorous, the selection of books has a “word” is a fuzzy notion, and ambiguities in
certain drawbacks. First, the sample reflects how it is defined invariably affect the results
not all published books, but only those that of any lexical census. Yet the size of the Eng-
Google or their partners deemed worthy lish lexicon remains a perennial question, and
of digital reproduction. Second, and more a working definition is needed if we hope to
important, books are inherently more distant address whether and how our vocabulary is
from the pulse of a culture than periodicals, growing. As such, we dealt with the ques-
in particular newspapers. Book publishing has tion as best we could: We explicitly defined
a substantial lag time to print; periodicals are the notion of “word” as a meaningful string
closer to real-time. Furthermore, as we move of alphabetic characters that is free of typo-
further away from news media, we see a shift graphical errors and that appears in the text
toward greater analysis, filtering, and a nar- of published books with a frequency greater
rowing of subjects. For these reasons, anal- than one part per billion. Crude though it may
yses of culture based on the written record be, this approach avoids many of the subjec-
should include a wide variety of texts. One of tive judgments associated with other attempts
the ultimate challenges to this type of research to measure the size of the lexicon. We agree
is representing information in a manner that with Morse-Gagné that the resulting count of
is effective and relevant to viewers within our over a million words should not be used to
culture. TIM SCHWARTZ justify anglophilic chauvinism.
Department of Visual Arts, University of California, San Diego, We disagree with Morse-Gagné’s argument
La Jolla, CA 92093–0327, USA. E-mail: tim.c.schwartz@ that our measurements of lexical size are con-
gmail.com sequences of the number of English speak-
ers and their publication rates. Our methods
Response require each word to appear with a frequency
WE THANK MORSE-GAGNÉ AND SCHWARTZ FOR of greater than 1 part per billion in the cor-
their Letters, and we are happy to have the responding time period. (Each time period is
opportunity to clarify. represented by many billions of words.) Thus,
Morse-Gagné questioned whether the size to use Morse-Gagné’s analogy, our count
AAAS is here – of the English lexicon is a meaningful statis- of “dinosaur footprints” included careful

increasing diversity in the


CORRECTIONS AND CLARIFICATIONS
scientific work force.
Review: “Homoplasy: From detecting pattern to determining process and mechanism of evolution” by D. B. Wake et al. (25
February, p. 1032). In the legend to Fig. 1B, the third sentence should have read: “One mode (which has evolved in two
independent lineages) elongates individual vertebrae (II); the alternative mode adds vertebrae (III) (48).” In the legend to
AAAS is working to ensure that Fig. 3, the fourth sentence should have read: “The phylogeny of Zingiberales indicates the relationships of the eight families
every student with an aptitude for with important character transitions (34).” The fifth sentence should have read: “For each family, the organs characteristic of
science, technology, engineer- each whorl are indicated: green, sepal; orange, petal; yellow, fertile stamen; light orange, petaloid stamen/staminode; blue,
ing, and mathematics gets an carpel.” The ninth sentence should have read: “(c and d) Monocostus (Costaceae) flower with distinct sepal and petal whorl
organs, fused outer and inner petaloid staminodes forming the labellum, and (d) a single fertile petaloid stamen from the
opportunity to pursue a chosen
inner stamen whorl.”
profession, no matter what the
challenges. For over 30 years Perspectives: “Life on low flame in hibernation” by G. Heldmaier (18 February, p. 866). In the fourth paragraph, the
AAAS’s ENTRY POINT! program basal metabolic rate of bears was incorrect. The correct figure is 0.276 ml O2 g −1 hour −1.
has placed talented, differently Editors’ Choice: “Extinction’s cause and effect” by N. S. Wigginton (4 February, p. 512). The field heading should have
abled students in paid intern- been Paleontology rather than Archaeology.
ships with leading scientific News Focus: “The Human Genome (patent) Project” by S. Kean (4 February, p. 530). Affymetrix was misidentified. The
employers. As a AAAS member company does not provide diagnostic services. It provides microarray and clinical application technologies, such as gene
your dues support these efforts. chips, for diagnostics work. The story should also have noted
that Affymetrix customers, not Affymetrix itself, must clear legal
If you’re not yet a AAAS member, rights for any gene patents when using Affymetrix products.
join us. Together we can make News Focus: “Going the distance” by E. Pennisi (28 January,
a difference. p. 395). The researcher in the picture (left) on page 395 was
incorrectly identified. He is Anders Kvist, who worked exten-
CREDIT: MAGNUS ELANDER

To learn more, sively with Blue, the bird who flew 16 hours in a wind tunnel.
visit aaas.org/plusyou/entrypoint News of the Week: “New high-tech screen takes carrier test-
ing to the next level” by J. Couzin-Frankel (14 January, p. 130).
A caption incorrectly states that Lesch-Nyhan syndrome, a rare
childhood disease, occurs when both parents carry the mutated
gene. In fact, the syndrome is an X-linked disorder, so only the
mother needs to be a carrier.

WorldMags 1 APRIL 2011 VOL 332 SCIENCE www.sciencemag.org


LETTERS

controls for the preponderance of mud.


Schwartz notes that our reliance on book
data might influence our results. We agree
that it will be important to expand our data
beyond books, as we emphasized in the final
section of our paper. However, digitization
at the culturomic scale—all books, all news-
papers, all magazines, all manuscripts—
remains in its infancy. We chose to study
books because they are one of the few types
of materials for which comprehensive data is
available. If thoughtful scholars like Morse-
Gagné and Schwartz continue to lend their
voices and pens to the cause, future scholars
will have a wider array of options.
EREZ LIEBERMAN AIDEN,1,2* JOSEPH P. PICKETT,3
JEAN-BAPTISTE MICHEL2,4*
1
Harvard Society of Fellows, Cambridge, MA 02138, USA.
2
Visiting Faculty, Google, Inc., Mountain View, CA 94043,
USA. 3American Heritage Dictionary, Houghton Mifflin Har-
court, Boston, MA 02116, USA. 4Department of Psychology,
Harvard University, Cambridge, MA 02138, USA.

*To whom correspondence should be addressed. E-mail:


erez@erez.com (E.L.A.); jbmichel@gmail.com (J.-B.M.)
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WorldMags
BOOKS ET AL.
HISTORY OF SCIENCE Mosque in Damascus.” In this context, he
might also have discussed the role played by
The Inquisitive West clergy such as Gregor Mendel and Thomas
Malthus in scientific discovery.
Saleem H. Ali Although Christianity had
Intellectual Curiosity and
its set of religious taboos, Huff
the Scientific Revolution

W
hy have some human societies ies, he argues, was con- argues that these were sur-
A Global Perspective
achieved greater scientific accom- veyed across the Muslim mounted through a higher liter-
plishments than others? In Intel- and Chinese realms but led by Toby E. Huff acy rate and the rise of news pub-
lectual Curiosity and the Scientific Revolu- to little further innovation. Cambridge University Press, lications. Perhaps adaptation was
tion, Toby Huff takes a cultural perspective to Although Huff gives Cambridge, 2011. 368 pp. $90, also inhibited by greater struc-
explain Western dominance in the sciences. credit to notable inquisitive £60. ISBN 9781107000827. tural inertia in Islam and Chinese
Paper, $27.99, £17.99.
Distinguishing engineering prowess (such researchers in the Islamic religious traditions. For example,
ISBN 9780521170529.
as the construction of hydrological systems) tradition (such as Ibn al- Muslim scientists, despite their
from scientific inquiry, he argues that a “curi- Haytham in optics and Ibn potential and intellect for innova-
osity deficit” in the Orient led to scientific Bajja in the science of motion), he takes the tion, were prevented from achieving break-
stagnation there. inability of such stalwarts to create a larger throughs in anatomy because of Islamic pro-
Huff (a sociologist who has turned to the scientific enterprise in their societies as indi- hibitions on dissection and an “aversion to
history of science) begins by laying out evi- cating a systemic cultural problem. The origi- artistic representation of the human body.”
dence for Western ascendance in the sciences nal scientific achievements within the Islamic In the case of China, Huff highlights the
during the late 16th and 17th centuries. Show- tradition largely occurred between the 10th work of Xu Guangqi as a proponent of sci-
ing little patience for those who romanticize and 12th centuries, when there was a willing- entific inquiry after his conversion to Chris-
oriental equivalence in scientific achieve- ness for collective learning and a transmis- tianity by Jesuit missionaries. The Chinese,
ment, he convincingly argues how key scien- sion of Greek texts to Western Europe. How- however, were reluctant to widely dissemi-
tific discoveries (from the laws of planetary ever, the commendable contributions of the nate the new knowledge, and much of the
motion to anatomical function) were largely “Arab masters” in areas such as trigonometry telescope’s use was relegated to ratifying
products of occidental science. He further were confined. Like earlier Greek discover- cosmological myths. Huff ’s account falters
challenges the notion of collective learning ies, Muslim contributions to science atro- slightly at this point, because he diminishes
through colonialism by noting that much of phied and did not lead to historically trans- the role of Christian evangelism in also hin-
the West’s colonial ventures in the East began formative inventions. Huff also convincingly dering scientific knowledge transfer. The
much later (in the 19th century). Focusing on dismisses specific claims of Arab scientific ulterior religious motives of the Jesuits may
Chinese and Islamic societies, he argues that influence on the West, such as the impact of have prompted the reluctance of the Chinese
most consequential knowledge transfer that Nasir al-Din al-Tusi on Copernicus. to embrace scientific transmission of knowl-
occurred was in fact from West to East, par- One senses a strong undercurrent of Prot- edge. Had the transmission of science been
ticularly by Jesuits in China. estant exceptionalism throughout Huff ’s for purely societal good, its reception may
A case study of the invention of the tele- narrative, in keeping with his earlier work have been different indeed.
scope provides the book’s core example of and admiration for Max Weber ( 1). He Huff does not explore ecological factors,
Western scientific superiority. Using rigorous claims that religious impediments to science such as those discussed by Jared Diamond
historical analysis, Huff carefully traces the were less substantial in Europe than in other (2), that might offer further insights into a
knowledge of optics that led to parts of the world Western propensity for scientific innovation.
this instrument and the subse- and that episodes, Nor does he consider developments in Africa,
quent transfers of the science such as Gali leo’s Mesoamerica, or Oceania.
and telescopes to China, India, conflicts with the Despite Intellectual Curiosity and the Sci-
and the Ottoman Empire. He Church, have been entific Revolution being somewhat circum-
offers ample allusions to pri- overplayed by histo- scribed by Huff’s sociological and geographic
mary texts and illustrations rians. Despite many causality, he should be commended for boldly
alongside critical appraisals tensions, Christian tackling a topic that deserves further histori-
of secondary commentaries. Europe had a greater cal analysis. While inquisitive impulses are
Huff supplements this core capacity to accept possible in any society, some have been able
case with considerations of the scientific enterprise. to embrace this essential scientific attribute
invention of the microscope, Referring to Mar- more so than others. Instead of feeling threat-
the development of microbiol- tin Luther’s Wit- ened by this revelation as a Western idea, all
ogy, and the evolution of early tenberg campaign, societies should strive for scientific excellence
physics (particularly pneumat- Huff comments that as a fundamentally human quest.
CREDIT: COURTESY TOBY HUFF

ics and electromagnetism). The “it is extremely dif-


knowledge of these discover- ficult to imagine an References
1. T. E. Huff, Max Weber and the Methodology of the Social
Islamic scholar” of Sciences (Transaction, New Brunswick, NJ, 1984).
The reviewer is at the Rubenstein School the 16th or 17th cen- 2. J. Diamond, Guns, Germs, and Steel: The Fate of Human
of Environment and Natural Resources,
University of Vermont, Burlington, VT Discovery device. Illustration from tury “posting such Societies (Norton, New York, 1997).

05405, USA. E-mail: saleem@alum. Johann Adam Schall von Bell’s Trea- a challenge on the
mit.edu tise on the Telescope (1626). door of the Great 10.1126/science.1204095

WorldMags www.sciencemag.org SCIENCE VOL 332 1 APRIL 2011 39


BOOKS ET AL.

SCIENCE IN FILM he calls the “law of accelerating returns,” the premature death of his father at age 58.
which is Moore’s law (the doubling of com- Fredric Kurzweil was a professional musician
puting power every year) on steroids, applied who, Ray’s mother says on camera, was never
The Immoralist to every conceivable area of science, technol- around while his charge was growing up. Like
ogy, and economics. father, like son—Kurzweil’s own workaholic
Michael Shermer While Ptolemy’s portrayal of Kurzweil tendencies in his creation of over a dozen
is unmistakably positive, to his credit he companies starting when he was 17 meant he

B
eware the prophet who proclaims that includes several critics from both religion and never really knew his father. As the film por-
the apocalypse, the resurrection, or science. Radio host Chuck Missler, a born- trays the tormented inventor, Kurzweil’s mis-
the biggest thing to happen to human- again Christian who heads sion in life seems more focused
ity ever will arrive in the prophet’s own life- the Koinonia Institute (“ded- Transcendent Man on resurrecting his patriarch
time. It is our natural inclination to assume icated to training and equip- than rescuing humanity.
The Life and Ideas
that we are special and that our generation ping the serious Christian to An especially lachrymose
of Ray Kurzweil
will witness the new dawn, but the Coperni- sojourn in today’s world”) moment occurs when Kurzweil
Barry Ptolemy, Director
can principle tells us that we are not special. proclaims: “We have a sce- is riffling through his father’s
Thus, the chances that even a science-based nario laid out that the world Ptolemaic Productions journals and documents in
and Therapy Studios, USA,
prophecy such as that proffered by the futur- is heading for an Armaged- a storage room dedicated to
2009. 83 minutes.
ist, inventor, and scientistic visionary extraor- don and you and I are going preserving his memory until
http://transcendentman.com/
dinaire Ray Kurzweil—that by 2029 we will to be the generation that’s the day that all these “data”
have the science and technology to live for- alive that is going to see all (including Ray’s own fading
ever—is unlikely to be fulfilled. this unfold.” Missler seems to be saying that memories) can be reconfigured into an arti-
Barry Ptolemy’s Transcendent Man is a Kurzweil is right about the second coming ficial intelligence simulacrum, thus reunit-
beautifully crafted and artfully edited docu- but wrong about what it is that is coming. ing father and son. Through heavy sighs and
mentary about Kurzweil and his quest to save Another religiously based admonition comes wistful looks, Kurzweil comes off not as a
humanity. If you enjoy contemplating the big from the Stanford University neuroscientist proselytizer on a mission but as a man tor-
questions in life from a scientific perspective, William Huribut, who identifies himself as a mented. It is, in fact, the film’s leitmotif. In
“practicing Christian.” He believes in one scene, Kurzweil wipes away a tear at his
immortality but not in the way Kurz- father’s grave site, in another he pauses over
weil envisions it and pronounces: photographs and looks longingly at memen-
“Death is conquered spiritually.” tos, and in yet another he recalls when his
From the science side, Neil Gersh- father, just days before his death, “uncharac-
enfeld, director of the Massachusetts teristically” phoned him, as if he’d had a pre-
Institute of Technology’s Center for monition. Although Kurzweil says he is opti-
Bits and Atoms, sagely notes: “What mistic and cheery about life, he can’t seem
Ray does consistently is to take a to stop talking about death: “It’s such a pro-
whole bunch of steps that everybody foundly sad, lonely feeling that I really can’t
agrees on and take principles for bear it,” he admits. “So I go back to thinking
extrapolating that everybody agrees about how I’m not going to die.” One won-
on and show they lead to things that ders how much of life he is missing by over-
nobody agrees on.” Likewise, the thinking death and how burdensome it must
futurist Kevin Kelly, who has painted surely be to imbibe over 200 supplement
a much more realistic portrait of what tablets a day and have your blood tested and
you will love this film. Accompanied by the our futures may (or may not) hold (1), com- cleansed every couple of months, all in an
eerily haunting music of Philip Glass (who, ments that “the precursors of those technolo- effort to reprogram the body’s biochemistry.
appropriately enough, also scored Errol Mor- gies that would have to exist simply are not There is something almost religious about
ris’s film The Fog of War—about another here.” Although he find’s Kurzweil’s expecta- Kurzweil’s scientism. He notes similarities
bigger-than-life character who thought he tion “heartwarming,” he predicts that “it isn’t between his goals and those of the world’s
could mold the world through data-driven going to happen.” While Kelly agrees that religions: “the idea of a profound transforma-
decisions, Robert McNamara), Transcen- Kurzweil’s exponential growth curves are tion in the future, eternal life, bringing back
CREDIT: RAY KURZWEIL/COURTESY TRANSCENDENT MAN

dent Man pulls viewers in through Kurzweil’s accurate, he holds that the conclusions and the dead.” Although the film never discloses
vision of a future in which we merge with especially the inspiration drawn from them his religious beliefs (he was raised by Jewish
our machines and vastly extend our longev- are not. He identifies Kurzweil as “a modern- parents as a Unitarian Universalist), in a (pre-
ity and intelligence to the point where even day prophet” for whom “nothing can waiver sumably) unintentionally humorous moment
death will be defeated. That point is Kurz- his absolutely certainty.” that ends the film, Kurzweil reflects on the
weil’s “singularity,” and he arrives at the 2029 The film is clearly intended as an uplifting god question and answers it himself: “Does
date by extrapolating curves based on what celebration of all the ways science and tech- God exist? I would say, ‘Not yet.’” Cheeky.
nology have enriched and are going to enrich
our lives. I don’t know if it is the music, the References
The reviewer, the author of The Mind of the Market, is at 1. K. Kelly, What Technology Wants (Viking, New York,
Claremont Graduate University and Skeptic magazine,
cinematography, or the subject himself, but 2010).
Post Office Box 338, Altadena, CA 91001, USA. E-mail: I found Transcendent Man to be a sad film
mshermer@skeptic.com about a genius who has been in agony since 10.1126/science.1205601

WorldMags
40 1 APRIL 2011 VOL 332 SCIENCE www.sciencemag.org
POLICYFORUM
CONSERVATION

Economic Importance of Bats Insectivorous bat populations, adversely


impacted by white-nose syndrome and wind

in Agriculture turbines, may be worth billions of dollars


to North American agriculture.

Justin G. Boyles,1* Paul M. Cryan,2 Gary F. McCracken,3 Thomas H. Kunz4

W
hite-nose syndrome (WNS) and At the same time, bats of several migra- Economic Impact
the increased development of tory tree-dwelling species are being killed Although much of the public and some
wind-power facilities are threaten- in unprecedented numbers at wind turbines policy-makers may view the precipitous
ing populations of insectivorous bats in North across the continent (6, 7). Why these spe- decline of bats in North America as only
America. Bats are voracious predators of noc- cies are particularly susceptible to wind tur- of academic interest, the economic conse-
turnal insects, including many crop and forest bines remains a mystery, and several types quences of losing so many bats could be
pests. We present here analyses suggesting of attraction have been hypothesized (6). substantial. For example, a single colony
that loss of bats in North America could lead There are no continental-scale monitor- of 150 big brown bats (Eptesicus fuscus)
to agricultural losses estimated at more than ing programs for assessing wildlife fatali- in Indiana has been estimated to eat nearly
$3.7 billion/year. Urgent efforts are needed to ties at wind turbines, so the number of bats 1.3 million pest insects each year, possibly
educate the public and policy-makers about killed across the entire United States is dif- contributing to the disruption of popula-
the ecological and economic importance of ficult to assess. However, by 2020 an esti- tion cycles of agricultural pests (8). Other
insectivorous bats and to provide practical mated 33,000 to 111,000 bats will be killed estimates suggest that a single little brown
conservation solutions. annually by wind turbines in the Mid-Atlan- bat can consume 4 to 8 g of insects each
tic Highlands alone (7). Obviously, mor- night during the active season (9, 10), and
Infectious Disease and Wind Turbines tality from these two factors is substantial when extrapolated to the one million bats
Insectivorous bats suppress populations of and will likely have long-term cumulative estimated to have died from WNS, between
nocturnal insects (1, 2), but bats in North impacts on both aquatic and terrestrial eco- 660 and 1320 metric tons of insects are no
America are under severe pressure from systems (5, 7). Because of these combined longer being consumed each year in WNS-
two major new threats. WNS is an emerg- threats, sudden and simultaneous population affected areas (11).
ing infectious disease affecting populations declines are being witnessed in assemblages Estimating the economic importance of
of hibernating cave-dwelling bats through- of temperate-zone insectivorous bats on a bats in agricultural systems is challenging,
out eastern North America (3). WNS is likely scale rivaled by few recorded events affect- but published estimates of the value of pest
caused by a newly discovered fungus (Geomy- ing mammals. suppression services provided by bats ranges
ces destructans). This fungus infects
the skin of bats while they hibernate
and is thought to trigger fatal altera-
tions in behavior and/or physiology
(e.g., premature depletion of energy
reserves) (3, 4). Since February 2006,
when WNS was first observed on bats
in upstate New York, G. destructans
has spread west of the Appalachian
Mountains and into Canada. To date,
over one million bats have probably
died, and winter colony declines in
the most affected region exceed 70%
(5). Populations of at least one spe-
cies (little brown bat, Myotis lucifu-
gus) have declined so precipitously
that regional extirpation and extinc-
tion are expected (5).
1
Department of Zoology and Entomology, Uni-
versity of Pretoria, Pretoria 0002, South Africa.
2
U.S. Geological Survey, Fort Collins Science
Center, Fort Collins, CO 80526, USA. 3Depart- 0–1020 3400–4800 8700–11000 17000–20000 29000–36000
ment of Ecology and Evolutionary Biology, Uni-
1020–2100 4800–6600 11000–14000 20000–24000 36000–50000
versity of Tennessee, Knoxville, TN 37996, USA.
4
Center for Ecology and Conservation Biology, 2100–3400 6600–8700 14000–17000 24000–29000 50000–73000
Department of Biology, Boston University, Bos-
ton, MA 02215, USA. The worth of insectivorous bats. Estimated annual value of insectivorous bats in the agricultural industry at the
*Author for correspondence. E-mail: jgboyles@ county level. Values (×$1000 per county) assume bats have an avoided-cost value of ~$74/acre of cropland (12).
zoology.up.ac.za (See SOM for details.)

WorldMags www.sciencemag.org SCIENCE VOL 332 1 APRIL 2011 41


POLICYFORUM

from about $12 to $173/acre (with a most wind turbines continues unabated, we can of new threats and at assessing their economic
likely scenario of $74/acre) in a cotton-dom- expect noticeable economic losses to North and ecological importance. We as scientists
inated agricultural landscape in south-central American agriculture in the next 4 to 5 years. should also make concerted efforts to develop
Texas (12). Here, we extrapolate these esti- and use more effective methods for educating
mates to the entire United States as a first Policy the public and policy-makers about the eco-
assessment of how much the disappearance A recently stated goal of the United Nations system services provided by bats.
of bats could cost the agricultural industry Environment Programme is to demonstrate Bats are among the most overlooked, yet
[see supporting online material (SOM)]. the value of biodiversity to policy-makers economically important, nondomesticated
Assuming values obtained from the cot- and the public (17). In keeping with this goal, animals in North America, and their conser-
ton-dominated agroecosystem in Texas, and we hope that the scale of our estimates and vation is important for the integrity of ecosys-
the number of acres of harvested cropland the importance of addressing this issue will tems and in the best interest of both national
across the continental United States in 2007 resonate both with the general public and and international economies. In our opin-
(13), we estimate the value of bats to the agri- policy-makers. Bats provide substantial eco- ion, solutions that will reduce the popula-
cultural industry is roughly $22.9 billion/ system services worldwide, and their benefits tion impacts of WNS and reduce the mortal-
year. If we assume values at the extremes of to human economies are not limited to North ity from wind-energy facilities are possible in
the probable range (12), the value of bats may America. For example, pioneering research the next few years, but identifying, substan-
be as low as $3.7 billion/year and as high as in tropical ecosystems shows the impor- tiating, and applying solutions will only be
$53 billion/year. These estimates include the tance of plant-visiting bats in the pollination fueled in a substantive manner by increased
reduced costs of pesticide applications that are of valuable fruit crops (18, 19). Although the and widespread awareness of the benefits of
not needed to suppress the insects consumed economic impacts of mass mortality of bats insectivorous bats among the public, policy-
by bats (12). However, they do not include associated with WNS appear to be confined, makers, and scientists.
the “downstream” impacts of pesticides on at present, to North America, wind turbines
ecosystems, which can be substantial (14), or are also causing bat fatalities in Europe (20), References
1. M. B. Kalka, A. R. Smith, E. K. V. Kalko, Science 320,
other secondary effects of predation, such as and the potential for WNS to spread to other 71 (2008).
reducing the potential for evolved resistance parts of the world is unknown. 2. K. Williams-Guillén, I. Perfecto, J. Vandermeer, Science
of insects to pesticides and genetically modi- We suggest that a wait-and-see approach 320, 70 (2008).
fied crops (15). Moreover, bats can exert top- to the issue of widespread declines of bat pop- 3. D. S. Blehert et al., Science 323, 227 (2009).
4. P. M. Cryan, C. U. Meteyer, J. G. Boyles, D. S. Blehert,
down suppression of forest insects (1, 2), but ulations is not an option because the life his- BMC Biol. 8, 135 (2010).
our estimated values do not include the ben- tories of these flying, nocturnal mammals— 5. W. F. Frick et al., Science 329, 679 (2010).
efit of bats that suppress insects in forest eco- characterized by long generation times and 6. P. M. Cryan, R. M. R. Barclay, J. Mammal. 90, 1330 (2009).
7. T. H. Kunz et al., Front. Ecol. Environ 5, 315 (2007).
systems because economic data on pest-con- low reproductive rates—mean that population 8. J. O. Whitaker, Jr., Am. Midl. Nat. 134, 346 (1995).
trol services provided by bats in forests are recovery is unlikely for decades or even centu- 9. E. L. P. Anthony, T. H. Kunz, Ecology 58, 775 (1977).
lacking. Even if our estimates are halved or ries, if at all. Currently, there are no adequately 10. A. Kurta, G. P. Bell, K. A. Nagy, T. H. Kunz, Physiol. Zool.
62, 804 (1989).
quartered, they clearly show how bats have validated or generally applicable methods for
11. J. G. Boyles, C. K. R. Willis, Front. Ecol. Environ 8, 92
enormous potential to influence the econom- substantially reducing the impacts of WNS (2010).
ics of agriculture and forestry. or wind turbines on bat populations. To date, 12. C. J. Cleveland et al., Front. Ecol. Environ 4, 238 (2006).
Although adverse impacts of WNS on bat management actions to restrict the spread of 13. USDA, 2007 Census of Agriculture: United States
Summary and State Data, vol. 1, Geographic Area Series
populations have occurred relatively rapidly, WNS have been directed primarily toward (AC-07-A-51, USDA, Washington, DC, 2009).
impacts of wind energy development appear limiting anthropogenic spread (e.g., cave and 14. D. Pimentel, in Integrated Pest Management: Innovation-
to pose a more chronic, long-term concern. mine closures and fungal decontamination Development Process, R. Peshin and A. K. Dhawan, Eds.
(Springer Media, Houten, Netherlands, 2009),
WNS has caused rapid and massive declines protocols) (21). Other proactive solutions for pp. 89–111.
of hibernating bats in the northeastern United understanding and ameliorating the effects of 15. P. Federico et al., Ecol. Appl. 18, 826 (2008).
States, where this disease has persisted for at WNS include developing improved diagnos- 16. D. L. Elliot, C. G. Holladay, W. R. Barchet, H. P. Foote,
least 4 years (5). Thus, the coming growing tics to detect early-stage infections and fun- W. F. Sandusky, Wind Energy Resource Atlas of the United
States (Solar Energy Research Institute, U.S. Department
season may be the first in which the adverse gal distribution in the environment; defining of Energy, Golden, CO, 1986).
effects of this disease will become notice- disease mechanisms; investigating the poten- 17. The Economics of Ecosystems and Biodiversity,
able. Because of regional differences in crop tial for biological or chemical control of the www.teebweb.org/.
18. S. Bumrungsri, E. Sripaoraya, T. Chongsiri, K. Sridith,
production, the agricultural value of bats in fungus; and increasing disease resistance P. A. Racey, J. Trop. Ecol. 25, 85 (2009).
the U.S. Northeast may be comparatively through habitat modification, such as creation 19. S. Bumrungsri et al., J. Trop. Ecol. 24, 467 (2008).
small relative to much of the United States of artificial or modified hibernacula that are 20. J. Rydell et al., Acta Chiropt. 12, 261 (2010).
21. U.S. Fish and Wildlife Service, www.fws.gov/
(see the figure) (SOM). However, evidence less conducive to disease development and
whitenosesyndrome/.
of the fungus associated with WNS was transmission (11, 22). Other approaches, such 22. J. Foley, D. Clifford, K. Castle, P. Cryan, R. S. Ostfeld,
recently detected in the Midwest and Great as culling of infected bats have been widely Conserv. Biol. 25, 223 (2011).
Plains, where the estimates of the value of discussed and dismissed as viable options 23. T. G. Hallam, G. F. McCracken, Conserv. Biol. 25, 189
(2011).
bats to agriculture are substantial (see the for control (23). New research also shows 24. E. F. Baerwald, J. Edworthy, M. Holder, R. M. R. Barclay,
figure). Additionally, because this region has that altering wind turbine operations dur- J. Wildl. Manage. 73, 1077 (2009).
the highest onshore wind capacity in North ing high-risk periods for bats significantly 25. E. Arnett et al., Front. Ecol. Environ 16, (2010).
10.1890/100103
America, increased development of wind reduces fatalities (24, 25). Specific action
energy facilities and associated bat fatalities on these issues will benefit from scientific Supporting Online Material
in this region can be expected (16). Thus, if research carefully aimed at providing practi- www.sciencemag.org/cgi/content/full/332/6025/41/DC1

mortality of bats associated with WNS and cal conservation solutions for bats in the face 10.1126/science.1201366

WorldMags
42 1 APRIL 2011 VOL 332 SCIENCE www.sciencemag.org
PERSPECTIVES
IMMUNOLOGY
Hosts may modulate their immune response
by measuring a combination of signals from
Danger, Microbes, and Homeostasis pathogens and damaged tissue.

Brian P. Lazzaro1 and Jens Rolff 2

T
he immune system is conventionally ria, which have enormous importance to the In addition to displaying MAMPs, true
viewed as a means to fight infection. It health and physiology of the host (4), main- pathogens stimulate the release of danger
has become clear, however, that what tained? Studies in insect model systems sug- signals by damaging host cells or secreting
is considered the “immune” system has also gest that the joint presence of both MAMPs molecules that interfere with host biology.
evolved to maintain homeostasis and regulate and danger signals may be required to This combination of MAMPs and danger
commensal microbes that normally inhabit launch a true defense response (5) and that signals can override the homeostatic nega-
the body. Such varied functions demand insects have mechanisms for disregarding tive regulation of the insect immune system
nuanced and context-appropriate control MAMPs presented in the absence of patho- in tissues like the gut, resulting in a full-
of immune responses. The thoughts on how logical damage to the host. blown defense response that includes high
immunity becomes activated include two The animal gut is constantly exposed expression of antibiotic proteins and bio-
views: by recognition of “nonself ” molecules to potentially pathogenic bacteria that are chemicals (11–13). Interestingly, the lower
of infectious agents (1) or by recognition of ingested along with food. Yet, the gut is level of defense activity triggered even
“danger” signals—host molecules released also the most important compartment of by commensals stimulates gut stem cell
by damaged host cells (2). Empirical evidence immune-modulated regulation of beneficial activity and epithelial renewal ( 13),
supports both models, but also reveals their microbial communities that aid in digestion providing an unexpected mechanism by
limits. Insights from recent studies on insect and nutritional assimilation (4). Beneficial which hosts and microbes interact to effect
immune systems, which are generalizable to microbes in both vertebrate and insect guts host homeostasis.
vertebrates, suggest that the
two models may be compat-
ible. That is, a host determines Challenge Elicitors Host Host homeostasis
the balance of nonself elicitors
and danger signals to decide
when to activate the immune Wound Wound repair
Danger signals
system against pathogenic Reads the balance of
Pathogen (host) signals to mount Controls/
infection while also maintain- eliminates infection
appropriate response
ing healthy relationships with Symbiont MAMP signals
commensals. (microbe) Maintains symbionts
Bacterial associations
with their hosts can be ben-
eficial, damaging, or benign,
depending on the context Elicitor ratio. Wounding, pathogen infection, and symbionts challenge the homeostasis of the host. A sterile wound generates
and the identity of play- exclusively danger signals, whereas symbionts display MAMPs without causing tissue damage that stimulates danger signals.
ers. It is generally believed Pathogens both display MAMPs and trigger danger signals, stimulating a robust immune response. The nature and strength of
that insects recognize bac- immune defense and homeostasis may be determined by the balance of danger and MAMP signals, combining the core tenets of
teria through the presence the danger and infectious nonself models.
of conserved molecules in
the prokaryotic cell wall called “microbe- display MAMPs that are recognized by the The reliance on the combination of
associated molecular patterns” (MAMPs). immune system, yet immune activity is mod- danger signals and MAMPS to stimulate
During infection, these molecules are rec- ulated such that the microbial community is immune reactions is not restricted to gut tis-
ognized by pattern recognition receptors actively regulated but not eliminated (6, 7). sues, but is a general property of defense
(PRRs) expressed by host cells, thereby trig- Studies in the fruit fly Drosophila melano- activation. In the waxmoth Galleria mel-
gering immune system activity and micro- gaster have found that some MAMPs (pepti- lonella, systemic bacterial and fungal infec-
bial elimination (1, 3). The insect MAMP- doglycan molecules) that are shed by bacte- tion results in damage to host cells and the
PRR model is analogous to the distinction ria in the gut induce expression of host pro- release of collagen fragments and nucleic
between self- and nonself molecules by the teins that degrade these MAMPs to a nonim- acids that synergize with MAMPs to stimu-
vertebrate immune system. But this concept munostimulatory form (6, 8). This negative- late an immune response (14). Extracellular
of immunity poses a puzzle: If the immune feedback loop dampens defense activity and collagen and nucleic acids are also danger
system is hardwired to readily recognize allows the host to regulate commensal abun- signals in vertebrates (15, 16). The expres-
and kill bacteria, how are symbiotic bacte- dance without entirely eliminating the sym- sion of genes that encode antimicrobial
bionts. Similar scenarios of the host inhib- peptides is induced by sterile wounding in
iting its defense response against mutualist insects, although this expression is transient
1
Department of Entomology, Cornell University, Ithaca, NY symbionts have been described in bacteri- in the absence of MAMPs (17).
2
14853, USA. Department of Animal and Plant Sciences,
University of Sheffield, Sheffield S10 2TN, UK. E-mail: jor@ omes, specialized organs where insects har- The use of danger signals in combina-
sheffield.ac.uk bor mutualistic bacteria (9, 10). tion with MAMPs may stem partly from an

WorldMags www.sciencemag.org SCIENCE VOL 332 1 APRIL 2011 43


PERSPECTIVES

economical approach to defense. In infec- themselves a sufficient cue for optimal reg- Sjöberg, E. Amir, P. Teggatz, M. Barman, M. Hayward,
tions, the damage caused by pathogenicity ulation of host immunity, but together they D. Eastwood, M. Stoel, Y. Zhou, E. Sodergren, G. M.
Weinstock, C. B. Williams, N. A. Bos, Nat. Immunol.
must be offset against the costs of deploying constitute a reliable indicator for modu- 11, 76 (2010).
an immune response (18). Rather than striv- lating the immune response to yield both 8. A. Zaidman-Rémy, M. Hervé, M. Poidevin, S. Pili-Floury,
ing to completely eliminate infections, the effective defense and homeostatic regula- M. S. Kin, D. Blanot, B. H. Oh, R. Ueda, D. Mengin-
immune system might manage a persistent tion of commensal microbial communities Lecreulx, B. Lemaitre, Immunity 24, 463 (2006).
9. C. Anselme, V. Pérez-Brocal, A. Vallier, C. Vincent-
infection at a low and nondamaging level (see the figure). In this scenario, the two Monegat, D. Charif, A. Latorre, A. Moya, A. Heddi,
(19). This is analogous to the concept of models of immune activation (1, 2) as trig- BMC Biol. 6, 43 (2008).
“economic injury level” in agricultural pest gered by nonself versus by danger signals 10. J. Wang, Y. Wu, G. Yang, S. Aksoy, Proc. Natl. Acad. Sci.
U.S.A. 106, 12133 (2009).
control, whereby pests are not eradicated need not be considered mutually exclusive,
11. P. Liehl, M. Blight, N. Vodovar, F. Boccard, B. Lemaitre,
but are suppressed to a threshold where the but could be merged into a single model PLoS Pathog. 2, e56 (2006).
cost of pest-driven damage is lower than the where the host reads the balance of sig- 12. E.-M. Ha, C.-T. Oh, Y. S. Bae, W.-J. Lee, Science 310, 847
cost of further control. MAMPs indicate the nals to mount an appropriate immunologi- (2005).
13. N. Buchon, N. A. Broderick, M. Poidevin, S. Pradervand,
presence of microbes, but if the microbes cal reaction.This measuring of signals may B. Lemaitre, Cell Host Microbe 5, 200 (2009).
are doing little or no damage to the host, allow the host to effectively fight an infec- 14. A. Vilcinskas, Virulence 1, 206 (2010).
the cost of immune activity may exceed the tion, while maintaining healthy relation- 15. R. Lande, J. Gregorio, V. Facchinetti, B. Chatterjee,
benefit of clearing the infection. The pre- ships with commensals. Y. H. Wang, B. Homey, W. Cao, Y. H. Wang, B. Su, F. O.
Nestle, T. Zal, I. Mellman, J. M. Schröder, Y. J. Liu,
sentation of damage-triggered danger sig- M. Gilliet, Nature 449, 564 (2007).
References and Notes
nals in conjunction with MAMPs, however, 1. R. Medzhitov, C. A. Janeway Jr., Science 296, 298 (2002). 16. S. Gambaryan, A. Kobsar, N. Rukoyatkina, S. Herterich,
indicates a severe infection that justifies the 2. P. Matzinger, Science 296, 301 (2002). S. Geiger, A. Smolenski, S. M. Lohmann, U. Walter,
expense of a defense response. 3. E. Ragan, C. An, H. Jiang, M. Kanost, in Insect Infection J. Biol. Chem. 285,18352 (2010).
and Immunity, J. Rolff, S. Reynolds, Eds. (Oxford Univ. 17. B. Lemaitre, J. M. Reichhart, J. A. Hoffmann, Proc. Natl.
The immune system cannot afford to Acad. Sci. U.S.A. 94, 14614 (1997).
Press, Oxford, 2009), pp. 34–48.
be rampantly stimulated by benign foreign 4. R. J. Dillon, V. M. Dillon, Annu. Rev. Entomol. 49, 71 18. B. P. Lazzaro, T. J. Little, Philos. Trans. R. Soc. Lond. B
molecules, but needs to determine whether (2004). Biol. Sci. 364, 15 (2009).
19. E. R. Haine, Y. Moret, M. T. Siva-Jothy, J. Rolff, Science
a signal indicates microbial nonself or dan- 5. R. E. Vance, R. R. Isberg, D. A. Portnoy, Cell Host Microbe
6, 10 (2009). 322, 1257 (2008).
ger. Insights from insect immunity point to 20. We thank O. Otti, A. Dobson, and S. Reynolds for
6. J. H. Ryu, S. H. Kim, H. Y. Lee, J. Y. Bai, Y. D. Nam, J. W.
the possibility that both types of elicitors Bae, D. G. Kee, S. C. Shin, E. M. Ha, W. J. Lee, Science comments on the manuscript.
may be important in combination. Perhaps 319, 777 (2008).
neither MAMPs nor danger signals are by 7. N. H. Salzman, K. Hung, D. Haribhai, H. Chu, J. Karlsson- 10.1126/science.1200486

CELL BIOLOGY

Phosphatase Inhibition Delays A small molecule, guanabenz, increases survival


of cells under stress.
Translational Recovery
R. Luke Wiseman1 and Jeffery W. Kelly1,2,3

I
n cells, various signaling pathways help ing or by attenuating new protein synthesis. for manipulating stress-signaling cascades
to maintain proteostasis—the proper The propagation of stress-response signal- through direct targeting of a property that
concentrations, folding, and function ing is often mediated by phosphorylation, emerges from these complex signaling cas-
of proteins. When a cell is under stress, or the addition of a phosphate group to the cades (an emergent property), allowing for
upstream “stress sensors” within these stress sensor and/or downstream signaling specific manipulation of stress signaling that
pathways are activated, initiating a signal- components. Because of the central impor- is independent of pathways involved in gen-
ing cascade that minimizes the misfold- tance of stress signaling pathways in main- eral cellular homeostasis.
ing and aggregation of proteins, which can taining the integrity of the cellular pro- One of the best-characterized stress-
lead to disease (1–3). Stress sensors often teome, manipulating these pathways has responsive signaling pathways is called the
respond to the accumulation of misfolded become an attractive strategy for preventing unfolded protein response. It maintains pro-
proteins within specific cell compartments the protein misfolding linked to numerous teostasis in the ER, where the secreted pro-
by activating the transcription of proteo- human diseases (4, 5). teome is folded (1, 7). The unfolded protein
stasis components, such as enzymes and On page 91 of this issue, Tsaytler et al. response comprises integrated signaling
“chaperone” proteins that assist with fold- take a step toward this goal. They demon- pathways that emanate from three trans-
strate that the selective inhibition of a stress- membrane stress sensors localized in the
1
Department of Molecular and Experimental Medicine, induced phosphatase complex involved in ER: IRE1, ATF6, and PERK. These sen-
Scripps Research Institute, La Jolla, CA 92037, USA. a stress-signaling pathway that controls sors are activated by the accumulation of
2
Department of Chemistry, Scripps Research Institute, La proteostasis in the endoplasmic reticulum misfolded proteins within the ER lumen.
Jolla, CA 92037, USA. 3Skaggs Institute for Chemical Biol-
ogy, Scripps Research Institute, La Jolla, CA 92037, USA. (ER) increases cellular survival (6). This Activation of IRE1 and ATF6 enhances pro-
E-mail: wiseman@scripps.edu; jkelly@scripps.edu novel approach demonstrates the potential tein folding capacity within the ER lumen

WorldMags
44 1 APRIL 2011 VOL 332 SCIENCE www.sciencemag.org
PERSPECTIVES

through transcriptional up-regulation of


Stress-induced kinase (e.g., PERK)
ER chaperones, folding enzymes, and com-
ponents of the ER-associated degradation
pathway. Activation of PERK induces the
selective phosphorylation of the α subunit P
of eukaryotic initiation factor 2 (eIF2α), eIF2α eIF2α Translation
Constitutive
which results in attenuation of ribosomal phosphatase complex
translation, thus reducing the load on the
ER proteostasis network (see the figure).
Phosphorylated eIF2α also selectively pro-
motes translation of the transcription fac- PP1 CReP
tor ATF4, which targets stress-responsive
ATF4
genes, including the transcription factor
CHOP. In turn, CHOP induces transcrip-
Stress-induced
tion of the protein phosphatase 1 regulatory phosphatase complex
subunit GADD34 (also called PPP1R15A),
which binds to the catalytic subunit of pro-
tein phosphatase 1. A heterodimer consist-
ing of the protein phosphatase 1 catalytic PP1 GADD34 CHOP
subunit and GADD34 regulatory subunit
selectively dephosphorylates eIF2α, thus
providing a negative feedback loop in the
PERK signaling cascade. This loop turns
off signaling and facilitates restoration of
ribosomal translation after ER stress. Guanabenz
Through expert detective work, Tsaytler
et al. correctly suspected that the small mole- Enhancing proteostasis. Guanabenz selectively inhibits the GADD34-mediated negative feedback loop of
cule guanabenz selectively binds to GADD34. PERK signaling through direct binding to GADD34, preventing its association with protein phosphatase 1
This prevents the assembly of the active pro- (PP1). As a result, guanabenz extends translational attenuation in response to ER stress, increasing chaper-
tein phosphatase 1–GADD34 heterodimer one-to-substrate ratios and alleviating protein misfolding within the ER lumen.
and delays recovery from stress-induced
translational attenuation (see the figure). signaling enhances mutant enzyme fold- the duration of stress responses exist, such
Although guanabenz binds the stress-induced ing capacity within the ER, increasing traf- as extending the duration of the cytosolic
regulatory subunit GADD34, it does not bind ficking and function of destabilized mutant heat-shock response by modulating histone
the constitutively expressed eIF2α regulatory proteins associated with lysosomal storage deacetylase (13). These agents could exhibit
subunit CReP (PPP1R15B), which similarly diseases (10). It would be interesting to see additive or synergistic properties with other
forms a heterodimer with protein phospha- whether prolonged PERK signaling, enabled stress-signaling pathway activators (10).
tase 1 and catalyzes eIF2α dephosphory- by guanabenz, is sufficient to restore mutant This strategy, targeting an emergent prop-
lation. Thus, guanabenz only slows eIF2α lysosomal enzyme proteostasis. Guanabenz erty of stress-responsive signaling, repre-
dephosphorylation during stress. In addition, also has the potential to modulate transla- sents an elegant opportunity for adapting
guanabenz does not induce cytotoxicity on its tional attenuation in response to other cellu- proteostasis to treat human diseases.
own, as do other inhibitors of eIF2α phospha- lar stresses, such as amino acid deprivation,
tases, such as calyculin A (8). Instead, gua- heme deficiencies, and oxidative insults that References
nabenz provides a boost to the endogenous activate alternative eIF2α kinases (11, 12). If 1. D. Ron, P. Walter, Nat. Rev. Mol. Cell Biol. 8, 519 (2007).
2. R. I. Morimoto, Genes Dev. 22, 1427 (2008).
PERK signaling pathway, extending the dura- so, it could potentially enhance cellular sur- 3. C. M. Haynes, D. Ron, J. Cell Sci. 123, 3849 (2010).
tion of translational attenuation and enabling vival in a manner analogous to that observed 4. W. E. Balch, R. I. Morimoto, A. Dillin, J. W. Kelly, Science
the recovery from ER stress by targeting by Tsaytler et al. 319, 916 (2008).
an emergent property of the PERK signaling Multiple groups have sought, or are 5. E. T. Powers, R. I. Morimoto, A. Dillin, J. W. Kelly, W. E.
Balch, Annu. Rev. Biochem. 78, 959 (2009).
cascade. seeking, small molecules that can activate 6. P. Tsaytler, H. P. Harding, D. Ron, A. Bertolotti, Science
Research has shown that PERK signaling a specific arm or arms of the unfolded pro- 332, 91 (2011); 10.1126/science/science.1201396.
is critical for maintaining ER proteostasis in tein response (4), and there is optimism that 7. M. Schröder, R. J. Kaufman, Annu. Rev. Biochem. 74, 739
pancreatic beta cells expressing high levels of these strategies will lead to the development (2005).
8. M. Boyce et al., Science 307, 935 (2005).
insulin (9). Thus, modulation of PERK sig- of drugs targeting numerous maladies. Mol- 9. A. Volchuk, D. Ron, Diabetes Obes. Metab. 12 (suppl. 2),
naling may alleviate ER stress associated with ecules such as guanabenz could represent 48 (2010).
increased insulin production. Consistent with an interesting category of these so-called 10. T. W. Mu et al., Cell 134, 769 (2008).
11. R. C. Wek, H.-Y. Jiang, T. G. Anthony, Biochem. Soc. Trans.
this hypothesis, Tsaytler et al. demonstrated proteostasis regulators, because they might
34, 7 (2006).
that guanabenz dose-dependently protects be able to make up for insufficient stress- 12. H. P. Harding et al., Mol. Cell 11, 619 (2003).
cells against ER stress induced by the over- responsive signaling by prolonging its dura- 13. S. D. Westerheide, J. Anckar, S. M. Stevens Jr., L. Sistonen,
expression of a destabilized mutant insulin tion. The regulation of stress-response path- R. I. Morimoto, Science 323, 1063 (2009).
protein. Similarly, recent evidence suggests ways is only partially understood, and it is
that increased activity of IRE1 and/or PERK likely that other strategies for extending 10.1126/science.1204505

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A Journal with Impact from AAAS, the publisher of Science
Science Translational Medicine
Integrating Medicine and Science
“The 2010 selection for the Nobel Prize in Physiology or Medicine
as well as the three Lasker Awards brought welcome opportunities
to celebrate truly groundbreaking translational research.”*

This quote illuminates the importance


of translational medicine discoveries. Indexed in
A recent journal article features the MEDLINE/PubMed
sequencing of fetal DNA from plasma
of a pregnant woman to permit prenatal,
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* Sci Transl Med 22 December 2010:
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DOI: 10.1126/scitranslmed.3001816

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IMMUNOLOGY

An Innate Role for IL-17 Human genetic mutations point to a cytokine


as critical for fighting a fungal infection.

Margarita Dominguez-Villar and David A. Hafler

I
nsight into the functional role of a par- C. albicans
ticular component of the immune sys- infection
tem, such as a cell type, cytokine, or Innate immune Adaptive immune
constituent of a signaling pathway, can be response response
gleaned from diverse human genetic muta-
tions that have naturally occurred in criti-
cal immune system processes. For example, Cytokines, chemokines
immune dysregulation polyendocrinopathy antimicrobial peptides Mucosal
enteropathy X-linked syndrome is an auto- epithelium
immune disease that was determined to be
secondary to dysregulation of a subset of
regulatory immune cells (CD4 subset of T
cells) caused by mutations in the FOXP3
gene. This discovery identified the tran- Natural killer cells
Macrophages IL-17A TH17 cells
scription factor FOXP3 in controlling nor- (CCR6, CCR4)
Monocytes IL-17F
mal immune responses and raised the issue
of defects in regulatory T cells in more com- Keratinocytes
mon human autoimmune disorders (1). On Proinflammatory
page 65 of this issue, Puel et al. (2) report Dendritic cells cytokines, chemokines, T cells (CD8)
tracing an abnormal immune response to T cells (γδ) costimulatory signals, T cells (γδ)
infection with the common fungus Candida antigen presentation
Neutrophils Eosinophils
albicans to mutations in components of a Proinflammatory
signaling pathway involving the cytokine cytokines, chemokines
interleukin-17 (IL-17).
Candida is a genus of commensal fungi Handling Candida. Upon infection with the fungus C. albicans, innate immune cells instruct the adaptive arm
found in the normal flora of the skin and of the human immune response to secrete IL-17, which acts on different cells that are essential for protection
mucosal surfaces of healthy individuals. Fun- against Candida.
gal infections (called candidiasis) with short-
lived symptoms of oral thrush or vaginitis, (5)] or hyper-immunoglobulin E syndrome tion against the infection (8). By contrast, in
though unpleasant, are not life-threatening. [caused by mutations in the gene encoding the chronic mucocutaneous candidiasis, cells of
However, in some individuals, Candida spp. transcription factor signal transducer and acti- the adaptive immune system mediate pro-
(C. albicans primarily) cause a persistent vator of transcription 3 (STAT3) (6)]. But Can- tection (9). The immune response against
infection either by infecting mucosal and epi- dida infection is also found as an isolated syn- Candida had long been thought to be driven
dermal surfaces (mucocutaneous candidiasis) drome in the absence of other severe infections primarily by T helper 1 (TH1) cells, because
or by disseminating in the blood (systemic or autoimmune disorders. In this case, called patients with chronic mucocutaneous candi-
candidiasis). Mucocutaneous candidiasis is chronic mucocutaneous candidiasis disease, diasis produced lower amounts of type 1 cyto-
typically a chronic syndrome, whereas sys- the underlying etiology is unknown (7). Puel kines, which are produced by TH1 cells (3)
temic candidiasis is acute. Chronic muco- et al. describe two genetic etiologies of this [such as interferon-γ (IFN-γ)], specifically in
cutaneous candidiasis is a clinically highly syndrome: an autosomal dominant mutation response to Candida spp. (10). More recently,
heterogeneous infection, as it is usually asso- in the gene encoding IL-17F, resulting in a with the discovery of the TH17 cell lineage,
ciated with other severe infections, particu- deficiency in this cytokine; and an autosomal studies in mice (11, 12) and humans (13)
larly in patients with acquired or inherited recessive mutation in the gene encoding inter- have revealed an important protective role for
T cell immunodeficiencies [such as HIV (3) leukin-17 receptor A (IL-17RA), resulting in TH17 cells in Candida infections. TH17 cells
and severe combined immunodeficiency (4)] a deficiency in this receptor for the cytokine. are a subset of T helper cells that secrete the
and/or autoimmune disorders. In a number These mutations clearly implicate the IL-17 cytokines IL-17A, IL-17F, IL-22, and IL-21,
of these cases, genetic alterations have been immune pathway in this disease. and are important for the host defense against
described in patients, such as in autoimmune Chronic mucocutaneous candidiasis dis- organisms at the mucosal barriers (14, 15).
CREDIT: Y. HAMMOND/SCIENCE

polyendocrine syndrome type 1 (caused by ease is characterized by infections of the With Candida infection, cells from the
mutations in the gene encoding the transcrip- nails, skin, and oral and reproductive muco- innate immune system can inhibit the infec-
tion factor autoimmune regulator (AIRE) sae in patients infected with C. albicans but tion directly themselves through antifun-
who have no signs of other infections or auto- gal activities (including secretion of antimi-
immune disorders. In systemic candidiasis, crobial peptides and engulfing microbes by
Department of Neurology and Immunobiology, Yale School
of Medicine, New Haven, CT 06520, USA. E-mail: david. cells of the innate immune system, particu- phagocytosis) (see the figure). These cells
hafler@yale.edu larly neutrophils, are essential for protec- also produce proinflammatory cytokines and

WorldMags www.sciencemag.org SCIENCE VOL 332 1 APRIL 2011 47


PERSPECTIVES

chemokines, and provide costimulatory and mononuclear cells. This mutation caused compared to healthy individuals. However,
antigen processing and presentation signals fibroblasts and leukocytes isolated from this it is unknown whether afferent defects in
to instruct the adaptive immune response patient to be unresponsive to IL-17A and IL- immune responses to Candida mediated by
cells to secrete IL-17. These IL-17–produc- 17F (homo- or heterodimers). In the second defects in IL-17A and IL-17F production by
ing cells are predominantly TH17 cells, but case report, the authors found a missense T cells, or loss of the efferent effects of IL-17
there are other cells from both the innate and mutation in IL17F gene in a multiplex fam- on mucosal and epithelial surfaces, underlie
adaptive immune system [(T cells (γδ), nat- ily with autosomal dominant inheritance of the chronic mucocutaneous fungal infection.
ural killer cells, neutrophils, T cells (CD8 chronic mucocutaneous candidiasis. This Although thrush and vaginitis occur in
subtype), and eosinophils] that also produce mutation was located in the cavity of the cyto- only a subset of the population, the findings
IL-17. Moreover, TH17 cells secrete several kine, a region implicated in receptor binding. of Puel et al. suggest that allelic variations in
chemokines (CXCL1, CXCL5, and IL-8) that Cytokines that were genetically engineered to key components of the IL-17 signaling path-
in turn act on cells of the innate immune sys- express the mutated form of the cytokine (in ways may predispose to common candidia-
tem, stimulating their migration to the site of the context of either an IL-17F homodimer or sis infection. Nevertheless, these data clearly
infection. IL-17 stimulates mucosal epithelial IL-17A–IL-17F heterodimer) did not bind to link evolution of the IL-17 pathway with host
cells to secrete proinflammatory cytokines, IL-17RA on fibroblasts. These mutant cyto- responses to Candida.
chemokines, and antimicrobial peptides. kines also altered the stimulation of cytokine
References
Puel et al. describe two case reports with secretion by peripheral blood mononuclear 1. V. Viglietta, C. Baecher-Allan, H. L. Weiner, D. A. Hafler,
two different genetic etiologies for these cells, suggesting that the mutation caused a J. Exp. Med. 199, 971 (2004).
chronic Candida infections. In one case, a partial loss of IL17F gene function. 2. A. Puel et al., Science 332, 65 (2011); 10.1126/
science.1200439.
child diagnosed with chronic mucocutane- The discovery of genetic defects in 3. L. de Repentigny, D. Lewandowski, P. Jolicoeur, Clin.
ous candidiasis had an autosomal recessive chronic mucocutaneous candidiasis that are Microbiol. Rev. 17, 729 (2004).
mutation in the gene encoding IL-17RA. related to TH17 cells supports previous data 4. C. Antachopoulos, Clin. Microbiol. Infect. 16, 1335 (2010).
5. J. Aaltonen et al., Nat. Genet. 17, 399 (1997).
This receptor binds both IL-17A and IL-17F, from mouse models and humans suggesting 6. Y. Minegishi et al., Nature 448, 1058 (2007).
and is expressed in multiple tissues, such as the importance of this cell type for protection 7. K. Eyerich, S. Eyerich, J. Hiller, H. Behrendt, C. Traidl-
vascular endothelial cells, peripheral T cells, against Candida infections. It further indi- Hoffmann, Eur. J. Dermatol. 20, 260 (2010).
8. L. Romani et al., Res. Immunol. 147, 512 (1996).
B cells, fibroblasts, lung, myelomonocytic cates that other genetic etiologies related to 9. H. R. Conti, S. L. Gaffen, Microbes Infect. 12, 518 (2010).
cells, and bone marrow stromal cells. The this lineage could underly chronic mucocu- 10. D. De Moraes-Vasconcelos et al., Clin. Exp. Immunol. 123,
authors sequenced genes encoding the key taneous candidiasis in other subjects, open- 247 (2001).
11. H. R. Conti et al., J. Exp. Med. 206, 299 (2009).
cytokines produced by TH17 cells from this ing an important field for developing thera- 12. L. Lin et al., PLoS Pathog. 5, e1000703 (2009).
patient (IL-22, IL-17A, and IL-17F) and their peutic strategies that target TH17 cells in these 13. K. Eyerich et al., J. Invest. Dermatol. 128, 2640 (2008).
corresponding receptors, and found a homo- patients. Puel et al. also demonstrate that the 14. S. J. Aujla et al., Semin. Immunol. 19, 377 (2007).
15. T. Korn, E. Bettelli, M. Oukka, V. K. Kuchroo, Annu. Rev.
zygotic nonsense mutation in the IL17RA percentage of total T cells (defined by CD3 Immunol. 27, 485 (2009).
gene that abrogated IL-17RA receptor expression) that secretes IL-17A was not
expression in fibroblasts and peripheral blood altered in the patients from both case reports 10.1126/science.1205311

MATERIALS SCIENCE

Impurities Enhance Semiconductor The electronic properties of free-standing


semiconductor nanocrystals can be tuned

Nanocrystal Performance by diffusing metallic impurities into them.

Y. Charles Cao

T
he semiconductor industry annually the fabrication of key transistor components tals. They present strong evidence that both
spends billions of dollars deliberately such as p-n junctions would not be possible n- and p-type nanocrystals were formed, as
adding atomic impurities, called dop- (1). Doping has had less impact on lower-cost well as insights into the electronic and opti-
ants, into very pure semiconductors. Dop- devices in which semiconductor nanocrys- cal effects of doping small nanocrystals (less
ants can make devices run faster by increas- tals may be used, such as solar cells, printable than 10 nm in diameter).
ing the number of negatively (n) or positively low-power devices, and light-emitting diodes The light emission and electronic struc-
(p) charged mobile carriers. They can also (2). Our knowledge of the doping effects on tures of a semiconductor nanocrystal can dif-
determine the predominant type of charge the electronic properties of semiconductor fer from those of bulk samples or thin films
carrier: electrons in n-type semiconductors, nanocrystals has been incomplete because of because of quantum confinement effects cre-
“holes” in p-type semiconductors (the dop- a lack of robust synthetic methods for dop- ated by its small size (4). These properties
ant atom accepts an electron, resulting in ing free-standing nanocrystals (as opposed have already led to applications; for example,
the formation of a “hole”). Without doping, to thin films of nanocrystals). On page 77 of colloidal semiconductor nanocrystals can be
this issue, Mocatta et al. (3) report a solution- used as fluorescent labels for the long-term
Department of Chemistry, University of Florida, Gainesville, phase synthesis of metallically doped, free- monitoring of biological pathways in living
FL 32611, USA. E-mail: cao@chem.ufl.edu standing indium arsenide (InAs) nanocrys- cells (5). It has been predicted that intentional

WorldMags
48 1 APRIL 2011 VOL 332 SCIENCE www.sciencemag.org
PERSPECTIVES

addition of impurities in nanocrystals A B


might lead to effects not observed in
the bulk. For example, magnetic impu- As
rities such as manganese (Mn) can be In3+ As In3+
3+
positioned inside a colloidal nanocrys- In In3+
tal with angstrom-scale precision (6)
to tune optical and magnetic proper-
ties. Nanocrystals doped with mag-
netic impurities are of interest for their As In3+ As As Ag+ As
potential use in spin-based electronic
devices (7). e–
Little progress has been made in Cu+
the n- or p-type impurity doping of
free-standing semiconductor nano- In3+ In3+
3+ 3+
crystals. Instead of using an impurity, In As In As
Shim and Guyot-Sionnest (8) made
undoped semiconductor nanocrystals
n-type by injecting extra electrons into
them. These extra electrons occupy Moving in. Lewis chemical structure diagrams illustrate a simplified two-dimensional view of the bonding in an InAs
the discrete conduction-band state of lattice containing metallic impurities. Mocatta et al. introduced metallic dopants, which modify the electronic prop-
erties of InAs nanocrystals, through diffusion. Bonding electrons are represented either by black lines or by paired
the nanocrystals (in bulk semiconduc- dots, whose color aims to indicate the atom to which it belongs. Plus signs indicate the lack of an electron in a bond-
tors, energy states of mobile electrons ing orbital. (A) A Cu impurity in an interstitial site in the InAs lattice donates valence electrons to the crystal and
form a conduction band that lies above causes n-type doping. (B) A substitutional Ag impurity occupying an indium site in the InAs lattice. The Ag causes
the states of the bound electrons in the InAs lattice disorder and introduces two electron acceptor sites into the lattice. The resulting deficiency of valence
valence band; the energy separation electrons causes p-type doping.
between them is the band gap). In stud-
ies of thin films of nanocrystals, Talapin and sure the electronic energy levels with respect be responsible for the electronic proper-
Murray (9) reported a general method to con- to the Fermi level, which is the energy of the ties of heavily doped semiconductor nano-
trol the carrier type in lead selenide nanocrys- highest state occupied with electrons (12). In crystals. A second issue concerns the loca-
tals with hydrazine treatments, and Bawendi general, shifts of the Fermi level up toward tion of the impurities within the doped InAs
and co-workers (10) switched InAs nano- the conduction band characterize a semicon- nanocrystals, as both copper and silver ions
crystals from n-type to p-type conduction via ductor as n-type, and shifts down toward the have large room-temperature solid-state dif-
doping with cadmium ions. However, the car- valence band characterize it as p-type. The fusion coefficients. Although some impurity
rier type determined in these transport experi- STS measurements show that the Cu-doped atoms may stay on the surface, the work of
ments is a collective property of many nano- InAs nanocrystals are indeed n-type, and that Mocatta et al. strongly argues that only the
crystals, and may not necessarily be the same the Ag-doped ones are p-type. impurities inside nanocrystals play a major
as the carrier type of the individual nanocrys- Modeling by Mocatta et al. suggests that role in determining the electronic properties
tals in the film. the electronic doping effects in small semi- of these nanocrystals. Despite these issues,
Mocatta et al. doped free-standing colloi- conductor nanocrystals strongly depend on the ability to control the position of the Fermi
dal InAs nanocrystals with metallic impuri- the low density of states in their conduc- level in semiconductor nanocrystals via
ties—copper (Cu) or silver (Ag)—by solid- tion band (an effect of quantum confine- impurity doping should enhance their perfor-
state diffusion (see the figure). Although Cu ment) as well as being “heavily doped”—a mance in electronic devices that can be pre-
and Ag impurities show similar diffusion 4-nm nanocrystal containing just one impu- pared by scalable bottom-up manufacturing.
properties inside the InAs crystal lattice, they rity atom is comparable to the most heav-
References
produce opposite electronic doping effects ily doped regime for a bulk semiconductor. 1. D. J. Norris, A. L. Efros, S. C. Erwin, Science 319, 1776
in bulk InAs. Copper is an n-type intersti- Their theoretical analysis reveals that the (2008).
tial impurity (it squeezes into empty sites heavy doping modifies the nanocrystal elec- 2. I. Gur, N. A. Fromer, M. L. Geier, A. P. Alivisatos, Science
between atoms in the crystal) and donates tronic states through the interplay of two fun- 310, 462 (2005).
3. D. Mocatta et al., Science 332, 77 (2011).
electrons that become the main charge car- damental effects. One is the creation of the 4. A. P. Alivisatos, Science 271, 933 (1996).
rier. Silver is a p-type substitutional impurity quantum-confined impurity band, which is 5. A. P. Alivisatos, W. W. Gu, C. Larabell, Annu. Rev. Biomed.
(it replaces an In ion), and the lower charge partially filled by charge carriers from the Eng. 7, 55 (2005).
6. Y. A. Yang, O. Chen, A. Angerhofer, Y. C. Cao, J. Am.
of its ion relative to In causes holes to be the impurity. The other is called band-tailing, Chem. Soc. 128, 12428 (2006).
main carrier (11). which is related to disordering of the crystal 7. R. Beaulac, L. Schneider, P. I. Archer, G. Bacher, D. R.
Optical measurements by Mocatta et al. lattice by the introduction of dopants. Gamelin, Science 325, 973 (2009).
8. M. Shim, P. Guyot-Sionnest, Nature 407, 981 (2000).
suggest that, unlike the n-type nanocrystals It will be interesting to correlate the
9. D. V. Talapin, C. B. Murray, Science 310, 86 (2005).
made by carrier injection (8), new impurity electronic nature of these individual n- or 10. S. M. Geyer et al., ACS Nano 4, 7373 (2010).
states are formed that increase the density of p-type semiconductor nanocrystals with the 11. C. S. Fuller, K. B. Wolfstirn, J. Electrochem. Soc. 114, 856
energy states near the semiconductor band carrier type in the thin films made of these (1967).
12. U. Banin, Y. W. Cao, D. Katz, O. Millo, Nature 400, 542
gap. They also used scanning tunneling spec- nanocrystals. One open question is whether (1999).
troscopy (STS) to characterize the doped InAs Stark effects (shifts in energy levels cre-
nanocrystals. This method can directly mea- ated by internal electrical fields) might also 10.1126/science.1203702

WorldMags www.sciencemag.org SCIENCE VOL 332 1 APRIL 2011 49


PERSPECTIVES

RETROSPECTIVE
The creative vision of a civil engineer to turn
universities into driving forces of innovation
George Bugliarello (1927–2011) spawned new design concepts for inner-city
renewal, industrial parks, and sustainable cities.
Ilan Juran and John Falcocchio

G
eorge Bugliarello, a creative engi- United States. It grew into member of many science and
neer, outstanding researcher, and a workforce of more than engineering organizations
dedicated educator, died on 18 Feb- 20,000 employees in finan- including The American
ruary at age 83, in New York. His range of cial, utilities, and communi- Society of Civil Engineers,
interests and expertise transcended many cation sectors (including the the Biomedical Engineering
disciplines, including civil engineering, bio- as “911” emergency system Society, and the American
medical engineering, urban development, of New York City). Among Society for the Advancement
science policy, water resources, and envi- his key decisions was creat- of Science.
ronmental science. His vision of the role of ing the Center for Advanced George’s expertise was
science, innovation, and education, coupled Technology in Telecommu- also called upon on an inter-
with a passion for turning his vision into real- nications in 1982, which national level, where he
ity, is reflected in today’s urban communities, continues to receive funding advised groups on science
forged through academic and industry inter- from the state of New York policy and urban and eco-
actions in ways that spur economic growth in return for transferring nomic development. These
and societal well-being, while respecting the research in technologies to New York compa- included committees for the U.S. National
quality of human life and the environment. nies for new applications. He also created a Academy of Sciences (NAS), the North
George was born in Trieste, Italy, in Center for Technology and Financial Services Atlantic Treaty Organization (NATO), the
1927. After graduating from the Univer- at Poly in 1994, with teaching and research NSF, and the U.S. National Institutes of
sity of Padua in 1951, he went to the United functions and a strong focus on users of tech- Health. He advised the U.S. Department of
States and earned master’s and Ph.D. doctoral nology in the financial industry. This fostered State in Venezuela and Central Africa, held
degrees in civil engineering at the University the first American academic master’s degree a Senior Faculty Fellowship for NATO at
of Minnesota (1954) and the Massachusetts program in Financial Engineering. The suc- the Technical University of Berlin, was a
Institute of Technology (1959). His career cess of MetroTech became the catalyst that member of the U.S.–Egypt Joint Consulta-
path included a faculty position at Carnegie George believed would transform downtown tive Committee of the NAS, and was on the
Mellon University and dean of engineering at Brooklyn into the new vibrant place of today. Science for Peace Steering Committee of
the University of Illinois at Chicago (1969– He was honored by the Engineering News- NATO. George served as Foreign Secretary
1973), where he explored the seamless meld- Record as one of “Those Who Made Marks,” of the U.S. National Academy of Engineer-
ing of biology, society, and machines, and and in 1994 he was awarded the New York ing (NAE), was a lifetime National Asso-
coined the term “biosoma.” City Mayor’s Award for Excellence in Sci- ciate of the National Academies, and was
George came to the Polytechnic Institute of ence and Technology. chair of the NAE Council’s International
New York University (Poly) where he served George’s diverse research interests ranged Affairs Committee.
as president for 21 years (1973–1994). His from stochastic simulations of hydrodynam- George was an elite humanistic explorer,
vision of rescuing the then Polytechnic Insti- ics to sustainable megacities in emerging whose creative scientific work and educa-
tute of Brooklyn from deep financial trouble countries. His 60 years of scientific work is tional dedication was often inspired by a holis-
began with its merger with the engineering reflected in more than 300 professional pub- tic quest for understanding the universe of the
school of New York University. He realized lications. He also founded (and was coedi- complex and intertwined relationships among
that for Poly to grow, it needed to change the tor of ) the journal Technology in Society. His biological, societal, environmental, and tech-
poor physical and economic character of its awards are many and include the Walter L. nological systems. For him, engineering was
neighborhood. He converted this problem Huber Civil Engineering Research Prize of the art of creating technology and systems as
into an opportunity for Poly. By recognizing the American Society of Civil Engineers in the processes that human societies devise to
that cities have historically been the product 1967 and the 2009 Marconi Society’s Beacon modify or preserve nature for their sustainable
CREDIT: POLYTECHNIC INSTITUTE OF NEW YORK UNIVERSITY

of technology, George carved a path to revi- of Light Award. development, and the capability of their stra-
talize downtown Brooklyn and placed Poly in He served on numerous national boards tegic integration in the design of the metrop-
a leading role to guide its renaissance. Two and committees in the United States, includ- olis to address future societal needs. His fel-
years after his arrival, he proposed the devel- ing the Advisory Committee for Science and low faculty and academic community believe
opment of a technology park. His tenacity in Engineering Education of the National Sci- that his scientific legacy and academic vision
developing and marketing this idea finally ence Foundation (NSF), the Board on Infra- will have a great impact on the next genera-
paid off in 1989, when ground was broken structure and the Constructed Environment of tion of multidisciplinary engineers and nur-
for MetroTech, the first modern university- the National Research Council, the National ture a professional culture that will inherently
industry research and technology park in the Academies committee on Megacities, the recognize the integration of bioenvironmental
National Committee on Science Education risks, societal inspirations, and technological
Standards and Assessment, and the Lawrence innovation as key elements for the sustainable
Urban Infrastructure Institute & Urban Utility Center,
Polytechnic Institute of New York University, Brooklyn, NY Livermore National Laboratory Engineer- development of urban society.
11201, USA. E-mail: ijuran@poly.edu ing Advisory Committee. George was also a 10.1126/science.1205706

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Early Detection of
Parkinson’s Disease:
The Challenges and Potential
of New Biomarkers

WEBINAR
Wednesday, April 27, 2011
12 noon ET, 9 am PT,
4 pm GMT, 5 pm UK

Ten years or more before the classic tremors of During this Webinar our distinguished panelists will:
Parkinson’s disease (PD) appear, the destruction • Explain the need for biomarkers for detecting early
of dopaminergic neurons in the brain’s nigrostriatal PD and how these biomarkers can be used in drug
pathway is well underway. Identifying biological development and clinical trials
markers (biomarkers) of PD in its earliest stages will
• Provide an overview of promising new biological and
be crucial for early intervention with therapeutics
neuroimaging markers
to prevent or even reverse loss of dopaminergic
neurons. Biomarkers for early PD could be used • Discuss the challenges and bottlenecks in the develop-
to identify patients at risk for PD or in the earliest ment of new biomarkers for PD and the role of the
stages of the disease and to assess the efficacy of Parkinson’s Progression Markers Initiative (PPMI).
new drugs or therapies. Biomarkers could also be
used to select appropriate patients for clinical trials
and to monitor disease progression or drug-induced Moderator: Brought to you by
remission in real time. So far, only one biomarker Science/AAAS and Science
Todd Sherer, Ph.D. Translational Medicine,
for PD called DaTscan—SPECT imaging of dopamine The Michael J. Fox Foundation for in association with the
transporters at dopaminergic nerve terminals in the Parkinson’s Research, New York, NY Michael J. Fox Foundation.
nigrostriatal pathway—has been approved by the
Participants:
FDA. Given the number of patients with PD (~1 mil-
Kenneth Marek, M.D.
lion in the United States and ~5 million worldwide), Institute for Neurodegenerative
developing new biomarkers for detecting the earliest Disorders, New Haven, CT
stages of this disease is imperative if new drugs and Michael G. Schlossmacher,
treatments are to be developed. M.D., FRCPC
University of Ottawa, Ottawa, Ontario

Register Now! Norbert Schuff, Ph.D.


Early bird discounts available University of California and VA Medical
Center, San Francisco, San Francisco, CA
before 25 March, 2011.
Andrew Siderowf, M.D., MSCE
Additional discounts for members University of Pennsylvania School of
and students/postdocs. Medicine, Philadelphia, PA
Questions can be submitted live during the
webinar or in advance by e-mail. To register, visit
www.sciencemag.org/webinar

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The GE & Science Prize for Young Life Scientists.


Because brilliant ideas build better realities.
Imagine standing on the podium at the Grand Hotel in Stockholm, making your
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REVIEW
How Reliable Is the Current Generation
of Predictions?
Climate-change impacts on biodiversity, both
Beyond Predictions: Biodiversity positive and negative, are already manifest in
recent widespread shifts in species ranges and
Conservation in a Changing Climate phenological responses (6, 7). Although human
land use remains the main driver of present-day
species extinction and habitat loss (8), climate
Terence P. Dawson,1 Stephen T. Jackson,2 Joanna I. House,3 Iain Colin Prentice,3,4,5 Georgina M. Mace4,6* change is projected to become equally or more
important in the coming decades (9, 10). As-
Climate change is predicted to become a major threat to biodiversity in the 21st century, sessing the biodiversity consequences of climate
but accurate predictions and effective solutions have proved difficult to formulate. Alarming change is complicated by uncertainties about the
predictions have come from a rather narrow methodological base, but a new, integrated science degree, rate, and nature of projected climate change
of climate-change biodiversity assessment is emerging, based on multiple sources and (11), the likelihood of novel and disappearing
approaches. Drawing on evidence from paleoecological observations, recent phenological and climates (12), the diversity of individual-species
microevolutionary responses, experiments, and computational models, we review the insights that responses to a broad suite of interacting climate
different approaches bring to anticipating and managing the biodiversity consequences of variables (6), and interactions of climate-change
climate change, including the extent of species’ natural resilience. We introduce a framework effects with other biotic factors (e.g., competition,
that uses information from different sources to identify vulnerability and to support the design of trophic relationships) and stressors (land use, in-
conservation responses. Although much of the information reviewed is on species, our framework vasive species, pathogens, pollutants) (13, 14).
and conclusions are also applicable to ecosystems, habitats, ecological communities, and Syntheses of climate change and biodiversity
genetic diversity, whether terrestrial, marine, or fresh water. for decision-makers, conservation organizations,
and governments (1, 2, 15) have relied heavily
larming predictions about the potential experiments, and mechanistic (process) modeling on empirical niche (or climate-envelope) mod-

A effects of future climate change are prompt-


ing policy responses at local to global
levels (1, 2). Because greenhouse gas emissions
based on ecophysiology and population biology.
These studies show a range of natural coping
mechanisms among populations exposed to cli-
eling and analog scenarios of climate space (4).
This approach uses statistical relationships be-
tween current climate variables and geographic
to date commit Earth to substantial climate change mate change, with diverse consequences for re- patterns of species distribution and/or abun-
in the coming decades (3), the potential for loss silience at local to global scales. The capacity to dance to define an “environmental space” asso-
of biodiversity, termination of evolutionary po- cope depends on both intrinsic factors (species ciated with a particular species. The models are
tential, and disruption of ecological services must biology, genetic diversity) and extrinsic factors then applied to climate projections from general
be taken seriously. Averting deleterious conse- (rate, magnitude, and nature of climatic change). circulation models (GCMs), yielding maps of
quences for biodiversity will require immediate Integration of multiple approaches and perspec- species ranges predicted under future climate
action, as well as strategic conservation planning tives is needed for more accurate information scenarios. Application of these models has led
for the coming years and decades. But how good about which species and habitats, in which places, to dire warnings of biodiversity loss (16). This
are our current predictions, and how fit are they are likely to be most at risk, as well as how has led in turn to calls for radical and immediate
for conservation planning purposes? conservation managers can leverage adaptive ca- intervention measures, including the redesign of
To date, assessments of climate-change im- pacities in natural systems to maximum advan- protected-area systems, development of new areas
pacts on biodiversity have largely been based on tage. There is a wealth of knowledge upon which for restoration and management, and human-
empirical niche (or climate-envelope) models (4). to draw. assisted migration (17, 18).
For most species, these models indicate large
geographic displacements and widespread ex- Box 1. Vulnerability in the context of climate and biodiversity.
tinctions. However, niche models are best suited
to identifying exposure to climate change, which Vulnerability is the extent to which a species or population is threatened with decline, reduced fitness,
is only one aspect of vulnerability. Assessing bio- genetic loss, or extinction owing to climate change. Vulnerability has three components: exposure (which
diversity consequences of climate change is a mul- is positively related to vulnerability), sensitivity (positively related), and adaptive capacity (negatively
tifaceted problem, requiring consideration of all related).
aspects of vulnerability: exposure, sensitivity, and Exposure refers to the extent of climate change likely to be experienced by a species or locale. Exposure
adaptive capacity (5) (see Box 1). Additional depends on the rate and magnitude of climate change (temperature, precipitation, sea level rise, flood
sources of evidence include observations of re- frequency, and other hazards) in habitats and regions occupied by the species. Most assessments of future
sponses to climate changes (both past and present), exposure to climate change are based on scenario projections from GCMs often downscaled with regional
models and applied in niche models.
Sensitivity is the degree to which the survival, persistence, fitness, performance, or regeneration of a
1
School of the Environment, University of Dundee, Dundee species or population is dependent on the prevailing climate, particularly on climate variables that are
DD1 4HN, Scotland, UK. 2Department of Botany, Program likely to undergo change in the near future. More sensitive species are likely to show greater reductions in
in Ecology, and Berry Biodiversity Conservation Center,
University of Wyoming, Laramie, WY 82071, USA. 3QUEST,
survival or fecundity with smaller changes to climate variables. Sensitivity depends on a variety of factors,
Department of Earth Sciences, University of Bristol, Bristol including ecophysiology, life history, and microhabitat preferences. These can be assessed by empirical,
BS8 1RJ, UK. 4Grantham Institute for Climate Change and observational, and modeling studies.
Division of Biology, Imperial College London, London SW7 Adaptive capacity refers to the capacity of a species or constituent populations to cope with climate
2AZ, UK. 5Department of Biological Sciences, Macquarie
change by persisting in situ, by shifting to more suitable local microhabitats, or by migrating to more
University, North Ryde, NSW 2109, Australia. 6Centre for
Population Biology, Imperial College London, Ascot SL5 suitable regions. Adaptive capacity depends on a variety of intrinsic factors, including phenotypic
7PY, UK. plasticity, genetic diversity, evolutionary rates, life history traits, and dispersal and colonization ability.
*To whom correspondence should be addressed. E-mail: Like sensitivity, these can be assessed by empirical, observational, and modeling studies.
g.mace@imperial.ac.uk

WorldMags www.sciencemag.org SCIENCE VOL 332 1 APRIL 2011 53


REVIEW

Direct observations

Paleoecological records Climate-envelope models

Empirical and Taxa


abundance
observational (%)

30

Summer
temp. (°C) 10
Winter temp. (°C)
5 -40
Integrated science of
climate-change
biodiversity assessment

Mechanistic

Ecophysiological models Population models

Experimental manipulations

Fig. 1. An integrated science of climate-change biodiversity assessment will between geographic patterns of species distributions and climate, and are best
draw from multiple sources and approaches. Each provides useful but incomplete suited for assessment of exposure. Mechanistic models such as population models
information on exposure, sensitivity, and adaptive capacity. Integration of these and ecophysiological models are diverse, require taxon-specific parameters, and
approaches will provide a more robust basis for vulnerability assessment and are often coupled. They are particularly effective in assessing sensitivity and
allocation of resources for conservation and adaptation. Direct observations, adaptive capacity. Experimental manipulations provide information on sensitivity
including long-term monitoring, are applicable at a broad range of scales and and adaptive capacity, and are valuable in parameterizing mechanistic models.
can be used to assess all aspects of vulnerability. Paleoecological records extend [Photo credits: direct observations (silverwashed fritillary, Argynnis paphia),
the observational foundation to encompass a broader range of rates, magni- www.learnaboutbutterflies.com; climate-envelope models, S. Brewer; population
tudes, and kinds of climate change. They can reveal adaptive capacity and risks. models, S. T. Jackson; experimental manipulations, A. K. Knapp; ecophys-
Climate-envelope (or niche) models are statistical models based on correlations iological models, W. P. Porter; paleoecological records, S. T. Jackson]

The heavy reliance of conservation manage- climate change to be faced varies widely among adjusting phenological responses in ways con-
ment and policy on a single scientific approach species. However, exposure is only one of many sistent with the relatively small climate changes
creates risks of policy or management failures, factors determining the impacts of climate change. of the past few decades (6, 26). Although some
particularly given that the underlying assump- Assessment of vulnerability must also include cli- species are undergoing rapid, widespread popu-
tions of that approach are under debate. Critiques mate sensitivity and adaptive capacity (5) (Box 1). lation declines, in most cases the primary drivers
center on the correlative nature of the niche mod- Complementary methodologies are available of decline involve land-use change and habitat
els, scale dependency, the difficulty of reliable that tell us much more about natural responses to fragmentation, biotic interactions, pathogens, and
extrapolation outside observed climate space, and climate change (Fig. 1). These indicate that bio- invasive species (8, 9). To date, there is more
failure to represent key ecological and evolution- diversity losses may not be as large as predicted evidence for climate-driven range expansion than
ary processes that could allow species to persist from niche models, although the rate of change for range contraction (27). It might appear that
in a heterogeneous landscape (13, 19–23). Niche and land use (habitat loss or destruction, harvesting) many species are coping with climate change.
models impart ease of use and power in explain- remain barriers to some natural response mecha- However, range contraction and population ex-
ing modern distributions (24), but their efficacy nisms. Approaches based on observations in the tirpation (local extinction) may be more difficult
in assessing extinction risk, delineating suitable present and the past, experiments, and new mod- to document than expansion and migration,
future habitats, and predicting ecological outcomes eling techniques are developing rapidly. Integration owing to undersampling of small or isolated
is unproven (25). of these approaches should provide the foundation populations, long-term local persistence of pop-
Niche models provide a tool for assessing for a robust science of climate-change assessment. ulations, and extinction lags (28). Extirpations
exposure to climate change as projected in var- already entrained by climate change may take
ious GCM scenarios (Box 1). Given the global Elements of Integrated Climate-Change years or decades to run their full course (29).
nature of projected climate changes (1), exposure Assessment for Biodiversity Detecting (or forecasting) species decline is
is inevitable for any species that has a finite ge- Ecological observations in real time. Many spe- challenging because the processes are not well
ographic distribution, although the amount of cies are altering their geographic ranges and understood, and species decline as well as loss

WorldMags
54 1 APRIL 2011 VOL 332 SCIENCE www.sciencemag.org
REVIEW
of ecosystem function may involve threshold environments will display novel combinations of applied alongside deeper understanding of the
transitions (30–32). climate variables (12). So far there is limited biological differences among species that de-
New knowledge emerges from real-time track- evidence of microevolutionary adaptive change termine their fate under climate change.
ing of species responses to climate change, but (33), perhaps because reliable methods to detect Intrinsic adaptive capacity for climate change.
direct observations are not, on their own, a suf- microevolution have rarely been applied (34, 35). Observations, experiments, and mechanistic mod-
ficient method for forecasting risks or the intrin- Furthermore, recent case studies where the causal els indicate that many species populations have
sic capacity of species and populations to adapt. processes driving population responses to climate the capacity to adjust to climate change in situ
It remains unknown whether the ongoing range change have been disentangled suggest that the via phenotypic plasticity (e.g., acclimation, ac-
expansions and phenological shifts will allow climate variables, and the way they interact with climatization, developmental adjustments) (Fig. 2)
species populations to survive, or whether these species life history, can be both complex and (35, 39) and microevolution (40, 41), and that
are transient responses in populations with re- context-specific (30, 31, 36–38). The use of ob- many populations are able to disperse locally to
duced fitness in the changed environment. Future servational evidence will therefore need to be suitable microhabitats (42, 43) or regionally to

Toleration Habitat shift Habitat shift Extinction

Juniperus osteosperma Pinus flexilis Picea glauca Picea martinezii

Alces alces Cervus elaphus Rangifer tarandus Megaloceros giganteus

Fig. 2. Representative modes of population and species-range response to modes. For example, since the last glacial maximum, populations of Juniperus
environmental changes since the last glacial maximum, documented for osteosperma and Alces alces have persisted at some sites (toleration), un-
selected North American conifer trees and Eurasian cervids. Populations of dergone habitat shifts (usually elevational or topographic) within some re-
many species have persisted in situ at individual sites since the last glacial gions, and colonized extensive new territory while disappearing from previously
maximum (toleration) and many have undergone habitat shifts, moving short occupied territory (migration). Alces alces has also undergone a severe genetic
distances (1 to 10 km) to sites with different aspects, slopes, elevations, and bottleneck. Differences among modes within and among species depend on
other attributes as the environment changed. Migrations of 100 to 1000 km rates, magnitudes, and geographic patterns of climatic change, the capacity of
are well documented for many species. Both migration and habitat shift are species populations to adapt (via phenotypic plasticity, evolution, and/or dis-
forms of environment tracking, in which species adjust their geographic lo- persal), and other factors (e.g., geographic barriers, and other stressors and
cations to track suitable environments. At least a few species have undergone interactions). References, additional examples, and detailed discussion are pro-
universal extinction (e.g., Megaloceros giganteus) owing to environmental vided in the supporting online material. [Photo credits: S. T. Jackson ( Juniperus
change; others have experienced loss of genetic diversity, usually associated osteosperma, Pinus flexilis, Picea glauca, Picea martinezii); A. D. Barnosky
with severe population bottlenecks (near-extinction episodes) (e.g., Picea (Megaloceros giganteus); www.grambophoto.com (Alces alces, Cervus elaphus,
martinezii). Species’ responses to climate change may consist of multiple Rangifer tarandus)]

WorldMags www.sciencemag.org SCIENCE VOL 332 1 APRIL 2011 55


REVIEW
newly suitable locales (44). Each of these adapt-
ive mechanisms has constraints, which may limit
the capacity of species and populations to keep

High
Low
Vulnerability
pace with high rates and magnitudes of climate high
change (35). These processes are, however, the
Preparedness Intensive
subject of an extensive ecological and evolution- intervention
ary literature, which has so far been underex-
ploited for determining adaptive capacity.

Adaptive capacity
Given the number and diversity of species Monitor • Ex situ conservation
climate and

Sensitivity
potentially under threat, the synthesis and ap- populations; • Reestablishment, rewilding
plication of existing evidence on adaptation will prepare • Assisted migration
provide necessary—but not sufficient—information contingency
on adaptive mechanisms and capacities. The en- plans with • Species-specific management
vironmental controls and absolute limits of pheno- increasing
• Habitat or landscape management
typic plasticity, and the environmental dependence intensity
• Passive management
of optimum phenotypes (45), must be determined
empirically for a range of species to predict in situ • Benign neglect
Low-intensity
ecological and evolutionary responses to envi- intervention
Low
High

Low
ronmental change (34, 35). Empirical and theo- vulnerability
retical studies of relevant ecological processes
(propagule dispersal, establishment, population Low High
growth, fecundity, mortality, metapopulation dy- Exposure to climate change and barriers to dispersal
namics) provide a basis for assessing response
times for local, regional, and continental adjust-
ments in distribution and abundance (46). This Fig. 3. The vulnerability of a species or ecosystem is based on its exposure to climate change, its sensitivity,
task can be simplified by using existing data and its inherent capacity to adapt to change. The relative balance of these different components of
and targeted studies of a range of representative vulnerability would lead to different management interventions. The x axis represents the degree of
exposure to climate change faced by species and communities (exogenous factors). This axis is largely
taxa with diverse life history patterns and func-
determined by the species’ or population’s geographical location, the rate and magnitude of climate
tional traits.
change anticipated for that region, and the size, cohesiveness, and connectivity of the species’ habitat
Biodiversity consequences of past climate within and beyond that region. The other two measures from the vulnerability framework, adaptive capacity
changes. Increasingly, geohistorical records and and sensitivity (see Box 1), are plotted together on the y axis. This axis is primarily determined by biological
paleoecological studies are being integrated with characteristics of species that influence their mobility, specificity, and sensitivity (endogenous factors).
independent paleoclimate records to reveal ef- These include, for example, physiological constraints, phenotypic plasticity, evolutionary potential, dispersal
fects of past climate changes (47, 48), which, in and growth capacity, and biotic interactions critical to persistence. The relative position of species and
some periods and regions, were as large and rapid ecosystems along the axes can inform decisions on appropriate research, monitoring, and management
as those projected for the future (49, 50). Al- strategies. Decisions are also likely to be affected by costs and assessments of benefits (e.g., an ecosystems
though possible future climates will be unlike service value or lower cost might shift strategies implemented toward the top right). Circled text denotes
those of the past, paleoecological records offer generic conservation responses. Specific conservation responses that will be appropriate under the different
vital information about how species responded to circumstances are discussed in the text. Species in the upper left corner have high sensitivity to climate
different rates and degrees of change, with nu- change but are expected to face relatively minor challenges. Such species are not a priority for intervention
merous case studies in terrestrial, freshwater, and unless there is a change in climate-change pressures or landscape permeability. Their potential vulnerability
marine ecosystems. The diverse outcomes for means that they need to be monitored to ensure that they are thriving and remain unthreatened, with
different taxa and life history types emphasize the contingency plans that can be deployed in a timely manner in case of change. Species with high exposure
range of past responses that are likely to be but low sensitivity and high adaptive capacity (lower right corner) can presumably cope with change, and
reflected in the present and future (Fig. 2). therefore need only low-intensity intervention as change becomes more extreme. Species in the upper right
Paleoecological observations can be further corner will have relatively high levels of both exposure and sensitivity; with decreasing adaptability, more
integrated with modern genetic and ancient DNA intensive and specific management will be required.
studies to assess the genetic consequences of
these dynamics (47, 51–53). By determining past
climate-driven losses in genetic and species di- cycle is only the most recent of at least 20 such long-distance migration and dispersal (59, 60),
versity at local to regional scales, and by iden- cycles during the past 2 million years. Ecolog- shifts along habitat gradients and mosaics (49, 61),
tifying the circumstances under which species ical and biogeographic responses to these cli- and rapid expansion under favorable conditions
have escaped extinction and populations have matic changes are particularly well documented (21). Many species have also undergone rapid
resisted extirpation, these studies can contribute for the past 10,000 to 20,000 years for many range contraction and widespread population de-
to assessments of adaptive capacity and vulner- regions; such responses included repeated re- cline (16, 49, 62). Low genetic diversity indicates
ability (Fig. 2). organization of terrestrial communities, changes that many species have passed through recent
All species or species groups living on in both the location and overall size of geo- genetic bottlenecks (63, 64). But few docu-
Earth today have persisted through a glacial- graphic ranges, and often rapid increases and mented species extinctions can be ascribed solely
to-interglacial transition 20,000 to 12,000 years decreases in sizes of local and regional popu- to climatic change (65–67). Megafaunal extinc-
ago that included rapid, high-magnitude climate lations (12, 49, 54–56). tions occurred in North America at a time of rapid
changes at all latitudes and in both terrestrial The fact that the biodiversity on Earth today climate change during the last deglaciation, but
and marine environments. This transition fol- passed through these events indicates natural re- human exploitation is also a possible cause (66).
lowed immediately upon a series of abrupt, high- silience and adaptive responses. Plant and animal Extinction of only one plant species (Picea
magnitude glacial-age climate changes with species have shown capacity for persistence in small critchfieldii) has been documented during the last
near-global impact (50). The last glacial-interglacial populations and microhabitats (52, 55, 57, 58), deglaciation (65).

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56 1 APRIL 2011 VOL 332 SCIENCE www.sciencemag.org
REVIEW
Developing an Integrated Science of about the relative urgency and the type of pacts (81) and ethical concerns (82). Despite
Climate-Change Biodiversity Assessment conservation action necessary. The diagonal axis these risks, such interventions may be necessary
The diverse sources of evidence discussed above in Fig. 3 broadly reflects increasing intensity of in some circumstances. It is not too early to
can be integrated in a vulnerability framework conservation interventions. This axis runs from debate whether, when, and how such strategies
(68). Vulnerability assessment has been sug- “laissez-faire” (i.e., let natural processes run their should be deployed (83). Finally, controlled ex
gested for prioritizing species at risk from climate course) to direct, targeted, and often intensive situ conservation, involving captive breeding and
change (5) and has been applied to both tax- “command and control” interventions. The most genetic manipulation in zoological and botanical
onomic and regional species groups (69, 70). The adaptable and/or insensitive species and those gardens and recently developed cryogenic seed
empirical foundation for trait-based climate-change with low exposure will need minimal interven- banks, may contribute to conserving species
vulnerability analysis is now starting to appear, tions with low-level monitoring, a strategy we or populations with a view to future release or
including species that were exposed to relatively call “benign neglect.” For example, in the United reintroduction.
rapid climate shifts during the Quaternary (47, 71) States and Africa, vast territories designated as The particular strategies deployed will de-
as well as some recent studies (44, 72–75). A wilderness areas or reserves are “managed” with pend on the circumstances of the species (Fig. 3)
combination of expert opinion and expectations a laissez-faire approach. Active management is and will also vary in the financial and other
from ecological and evolutionary theory has been restricted to sporadic rewilding (e.g., top-predator resources they require. The perceived conserva-
used to identify vulnerable traits for some groups reintroduction), low-impact eradication of inva- tion value of particular habitats and species will
(69, 76), including, for example, ecological spe- sive species, and removal of individuals danger- also play a part and may be informed by eco-
cialists at higher trophic levels, with long gen- ous to humans (e.g., rogue grizzly bears). These system service assessments. Thus, management
eration times, poor dispersal ability, and low designations may, of course, change in the future. decisions will depend on judgments of potential
reproductive output. Body mass is strongly cor- For example, it is likely that some ecosystems risks and benefits balanced against costs and
related with extinction risk and is often associated that currently receive minimal management, such available or anticipated resources. Decisions must
with other risk-promoting traits (e.g., delayed as boreal forests, may require more active man- balance tradeoffs. For example, creating perme-
reproductive maturity, small geographic range) agement under climate change. able landscapes to facilitate migration may be
(77). Large range sizes may imply a large pop- As exposure and sensitivity increase and more effective under climate change than inten-
ulation size and can act to buffer against habitat autonomous-response capability decreases, substan- sive management in “static” conservation areas
loss or fragmentation. A broad geographical dis- tial benefits may result from simply designating as climate change proceeds, but may risk further
tribution may not only protect against individual new protected areas and undertaking low-level spread of disease or invasive species. This as-
habitat patches becoming climatically unsuitable, habitat management to reinforce species’ intrin- sessment should aim to maximize the likelihood
but may also foster high genetic variability. How- sic dispersal and migration mechanisms. Analy- of the desired management outcome, minimize
ever, there are many exceptions to these general- ses based on niche models have prescribed this the financial costs, and assess associated risks.
izations, and paleoecological records suggest approach (15). Periodic reevaluation of ongoing
that they may break down under rapid climate and planned protected-areas strategies may be Outlook
change (49, 65). needed to maintain potential for species resilience Conservationists are increasingly concerned about
Today, many species will be required to dis- and mobility under climate change. For example, biodiversity disruption and loss as climate-change
perse rapidly through highly fragmented, human- dynamic placing of buffer zones, removal of bar- impacts intensify in the coming decades. So far
dominated landscapes in order to keep pace with riers, and establishment of corridors or “stepping the focus has mostly been on multispecies, place-
changing climate. Paleoecological evidence sug- stones” within a wider landscape may be neces- based predictions with emphasis on exposure to
gests that many plant species have responded to sary (78), although the definition, costs, and ben- climate change. Our review of the evidence from
past rapid climate changes with migration rates efits of connectivity are under debate (79). A paleohistory, current observations, experiments,
orders of magnitude higher than predicted by complementary strategy is to maintain high within- and models emphasizes the extent to which spe-
mean observed dispersal distances. This suggests region habitat heterogeneity (edaphic, topograph- cies vary in their vulnerability. This variation
a potential role for rare long-distance dispersal ic, or elevational), which provides more options represents perhaps our best hope for maintaining
(LDD) through the transportation of seeds in at- for both natural populations and conservation biodiversity and its associated ecological goods
mospheric updrafts and water courses, oceanic managers (80). and services in the future. Developing effective
currents, and dispersal by birds and animals. Hu- In any habitat or community, some species strategies will rely on improved understanding of
mans are very effective as LDD vectors and, like may require specific actions for their conserva- the nature of the climate threat to species, and the
natural LDD mechanisms, do not require contig- tion or to retain critical biological interactions. way that it interacts with their natural coping
uous habitat to establish or maintain connectivity Intermediate strategies—including intervention mechanisms. The rich history of ecological, evo-
between populations, perhaps facilitating conser- to arrest or divert natural succession or ecosystem lutionary, and paleontological field studies, brought
vation strategies. regime shifts, maintenance of specific habitats or together with relevant climate data and with
Given the evidence that the responses of spe- habitat diversity, and targeted interventions to appropriate evolutionary and ecological theory
cies and communities to climate change will be restore disrupted species interactions (e.g., polli- and modeling, has the potential to transform
highly variable, we need to move beyond pre- nator or plant-herbivore networks)—are now the way that we assess climate-change vulnera-
dictions of future range changes, which may over- widely used. Species-specific management may bility. More appropriate conservation actions will
estimate or underestimate risks in particular cases. be costly and intensive, but it can reverse the fate result from taking into account all three aspects of
Because of the variety of vulnerabilities and the of endangered species (8). vulnerability—species sensitivity, adaptive capac-
factors that contribute to them, a one-size-fits-all Intensive intervention strategies include as- ity, and exposure.
strategy risks failure. We advocate a combination sisted migration and translocation of species out- Many orthodox conservation practices, such
of strategies governed by assessment of vulner- side their native range (18). Reestablishment and as the restoration and protection of habitats and
ability and its three components—exposure, sensi- rewilding involve intensive habitat management the removal of anthropogenic pressures unrelated
tivity, and adaptive capacity—drawn from multiple to restore critical habitat types, with whole com- to climate, will continue to increase species and
lines of evidence. munities recreated from populations surviving ecosystem adaptive capacity to climate change.
Figure 3 displays species responses to climate elsewhere. These are generally considered to be Additional, more informed approaches will re-
change on two axes, based on a vulnerability high-risk strategies because of potentially nega- quire new research, especially to identify and
framework. This approach can inform managers tive ecological, evolutionary, and economic im- parameterize key ecological and evolutionary

WorldMags www.sciencemag.org SCIENCE VOL 332 1 APRIL 2011 57


REVIEW
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WorldMags
RESEARCH ARTICLES
vate sector research firm [International Data Cor-
poration (IDC)] to estimate the global hardware
capacity of digital ICT for the years 2007–2008
The World’s Technological Capacity (14). For digital storage, IDC estimates that in
2007 “all the empty or usable space on hard
to Store, Communicate, and drives, tapes, CDs, DVDs, and memory (volatile
and nonvolatile) in the market equaled 264

Compute Information exabytes” (14). During 2008, an industry and


university collaboration explicitly focused on in-
formation consumption (15) measured in hard-
Martin Hilbert1* and Priscila López2 ware capacity, words, and hours. The results are
highly reliant on media time-budget studies, which
estimate how many hours people interact with a
We estimated the world’s technological capacity to store, communicate, and compute information,
media device. The result obtained with this meth-
tracking 60 analog and digital technologies during the period from 1986 to 2007. In 2007,
odology was that computer games and movies
humankind was able to store 2.9 × 1020 optimally compressed bytes, communicate almost
represent 99.2% of the total amount of data
2 × 1021 bytes, and carry out 6.4 × 1018 instructions per second on general-purpose computers.
“consumed.”
General-purpose computing capacity grew at an annual rate of 58%. The world’s capacity for
Scope of our exercise. To reconcile these dif-
bidirectional telecommunication grew at 28% per year, closely followed by the increase in
ferent results, we focused on the world’s tech-
globally stored information (23%). Humankind’s capacity for unidirectional information
nological capacity to handle information. We do
diffusion through broadcasting channels has experienced comparatively modest annual growth
not account for uniqueness of information be-
(6%). Telecommunication has been dominated by digital technologies since 1990 (99.9% in
cause it is very difficult to differentiate between
digital format in 2007), and the majority of our technological memory has been in digital
truly new and merely recombined, duplicate in-
format since the early 2000s (94% digital in 2007).
formation. Instead, we assume that all informa-
tion has some relevance for some individual.
eading social scientists have recognized information resulted in the conclusion that “most Aside from the traditional focus on the transmis-

L that we are living through an age in which


“the generation of wealth, the exercise of
power, and the creation of cultural codes came to
of the total volume of new information flows is
derived from the volume of voice telephone traf-
fic, most of which is unique content” (97%);
sion through space (communication) and time
(storage), we also considered the computation of
information. We defined storage as the mainte-
depend on the technological capacity of societies because broadcasted television and most infor- nance of information over a considerable amount
and individuals, with information technologies as mation storage mainly consists of duplicate infor- of time for explicit later retrieval and estimated
the core of this capacity” (1). Despite this insight, mation, these omnipresent categories contributed the installed (available) capacity. We did not con-
most evaluations of society’s technological ca- relatively little. A storage company hired a pri- sider volatile storage in the respective inventory
pacity to handle information are based on either
qualitative assessments or indirect approxima-
tions, such as the stock of installed devices or the
economic value of related products and services
(2–9).
Previous work. Some pioneering studies have
taken a more direct approach to quantify the
amount of information that society processes
with its information and communication tech-
nologies (ICTs). After pioneering work in Japan
(10), Pool (11) estimated the growth trends of the
“amount of words” transmitted by 17 major com-
munications media in the United States from
1960 to 1977. This study was the first to show
empirically the declining relevance of print me-
dia with respect to electronic media. In 1997,
Lesk (12) asked, “How much information is
there in the world?” and presented a brief out-
line on how to go about estimating the global
information storage capacity. A group of research-
ers at the University of California at Berkeley
took up the measurement challenge between 2000
and 2003 (13). Their focus on “uniquely created”

1
Annenberg School of Communication, University of Southern
California, Los Angeles, CA 90089, USA; United Nations Eco-
nomic Commission for Latin America and the Caribbean (ECLAC).
2
Information and Communication Sciences Department, Open
University of Catalonia, Barcelona 08018, Spain.
*To whom correspondence should be addressed. E-mail:
mhilbert@usc.edu Fig. 1. The three basic information operations and their most prominent technologies.

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(such as RAM) because the ultimate end of vol- fined computation as the meaningful transforma- some two or three dozen categories of ICT over
atile memory is computation, not storage per se. tion of information and estimated the installed three consecutive years at most, our study en-
Communication was defined as the amount of (available) capacity. compasses worldwide estimates for 60 categories
information that is effectively received or sent by More precisely, as shown in Fig. 1, we dis- (21 analog and 39 digital) and spans over two
the user while being transmitted over a consid- tinguished among storage of information in bits, decades (1986–2007).
erable distance (outside the local area). This in- unidirectional diffusion through broadcasting in We obtained the technological capacity by
cludes those transmissions whose main purpose bits per second, bidirectional telecommunication multiplying the number of installed technological
consists in the overcoming of distances, not the in bits per second, computation of information by devices with their respective performances. All
local sharing of information (such as the distribu- general purpose computers in instructions per estimates are yearly averages, but we adjusted
tion of copies at a meeting, or communication second [or MIPS, million (or mega) instructions for the fact that the installed technological stock
through private local area networks). We took in- per second], and the estimated computational ca- of a given year is the result of an accumulation
ventory of the effective communication capacity pacity of a selected sample of application-specific process of previous years, whereas each year’s
(the actual amount of bits transmitted). We de- devices (MIPS). Whereas previous studies tracked technologies contribute with different perfor-
mance rates. We used 1120 sources and explain
our assumptions in detail in (16). The statistics
we rely on include databases from international
organizations [such as (17–22)], historical in-
ventories from individuals for commercial or
academic purposes [such as (23–26)], publicly
available statistics from private research firms
[such as (27, 28)], as well as a myriad of sales
and product specifications from equipment
producers. We filled in occasional blanks with
either linear or exponential interpolations, de-
pending on the nature of the process in question.
Frequently, we compared diverse sources for
the same phenomena and strove for reasonable
middle grounds in case of contradictions. In cases
in which specific country data were not available,
we aimed for a globally balanced outlook by
creating at least two international profiles, one for
the “developed” member countries of the Organ-
isation for Economic Co-operation and Develop-
ment (OECD) and another one for the rest of
the world.
Information, not hardware with redundant
data. Although the estimation of the global hard-
Fig. 2. World’s technological installed capacity to store information (table SA1) (16). ware capacity for information storage and com-
munication is of interest for the ICT industry
(14), we are more interested in the amount of
information that is handled by this hardware.
Therefore, we converted the data contained in
storage and communication hardware capaci-
ty into informational bits by normalizing on
compression rates. This addresses the fact that
information sources have different degrees of
redundancy. The redundancy (or predictability)
of the source is primarily determined by the con-
tent in question, such as text, images, audio, or
video (29, 30). Considering the kind of content,
we measured information as if all redundancy
were removed with the most efficient compres-
sion algorithms available in 2007 (we call this
level of compression “optimally compressed”).
Shannon (29) showed that the uttermost com-
pression of information approximates the entropy
of the source, which unambiguously quantifies
the amount of information contained in the mes-
sage. In an information theoretic sense (30), in-
formation is defined as the opposite of uncertainty.
Shannon (29) defined one bit as the amount of
information that reduces uncertainty by half (re-
garding a given probability space, such as letters
Fig. 3. World’s technological effective capacity to broadcast information in optimally compressed from an alphabet or pixels from a color scale).
megabytes MB per year, for 1986, 1993, 2000, and 2007; semi-logarithmic plot (table SA2) (16). This definition is independent of the specific task

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RESEARCH ARTICLES
or content. For example, after normalization on Before the digital revolution, the amount of terms (from 8.7 to 19.4 optimally compressed
optimally compressed bits we can say things like stored information was dominated by the bits petabytes).
“a 6-cm2 newspaper image is worth a 1000 words” stored in analog videotapes, such as VHS cas- Communication. We divided the world’s tech-
because both require the same average number settes (Fig. 2). In 1986, vinyl long-play records nological communication capacity into two
of binary yes/no decisions to resolve the same still made up a considerable part (14%), as did broad groups: One includes technological sys-
amount of uncertainty. analog audio cassettes (12%) and photography tems that provide only unidirectional downstream
Normalization on compression rates is essen- (5% and 8%). It was not until the year 2000 that capacity to diffuse information (referred to as
tial for comparing the informational performance digital storage made a notable contribution to our broadcasting), and one provides bidirectional up-
of analog and digital technologies. It is also in- technological memory, contributing 25% of the stream and downstream channels (telecommu-
dispensable for obtaining meaningful time series total in 2000. Hard disks make up the lion share nication). The ongoing technological convergence
of digital technologies because more efficient of storage in 2007 (52% in total), optical storage between broadcasting and telecommunication
compression algorithms enable us to handle more contributed more than a quarter (28%), and is blurring this distinction, as exemplified by the
information with the same amount of hardware. digital tape roughly 11%. Paper-based storage case of digital television, which we counted as
For example, we estimated that a hard disk with a solutions captured a decreasing share of the total broadcasting even though it incorporates a small
hardware performance of 1 MB for video storage (0.33% in 1986 and 0.007% in 2007), even though but existent upstream channel (such as video-on-
was holding the equivalent of 1 optimally com- their capacity was steadily increasing in absolute demand).
pressed MB in 2007 (“optimally compressed” with
MPEG-4) but only 0.45 optimally compressed
MB in 2000 (compressed with MPEG-1), 0.33 in
1993 (compressed with cinepack), and merely
0.017 optimally compressed MB in 1986 (sup-
posing that no compression algorithms were used).
Given that statistics on the most commonly used
compression algorithms are scarce, we limited our
estimations of information storage and communi-
cation to the years 1986, 1993, 2000 and 2007
[(16), section B, Compression].
Conventionally, bits are abbreviated with a
small “b” (such as in kilobits per second: kbps)
and bytes (equal to 8 bits) with a capital “B”
(such as in megabyte: MB). Standard decimal
prefixes are used: kilo- (103), mega- (106), giga-
(109), tera- (1012), peta- (1015), exa- (1018), and
zetta- (1021).
Storage. We estimated how much informa-
tion could possibly have been stored by the 12
most widely used families of analog storage
technologies and the 13 most prominent families
of digital memory, from paper-based advertise-
ment to the memory chips installed on a credit
card (Fig. 2). The total amount of information Fig. 4. World’s technological effective capacity to telecommunicate information (table SA2) (16).
grew from 2.6 optimally compressed exabytes
in 1986 to 15.8 in 1993, over 54.5 in 2000, and
to 295 optimally compressed exabytes in 2007.
This is equivalent to less than one 730-MB CD-
ROM per person in 1986 (539 MB per person),
roughly 4 CD-ROM per person of 1993, 12 CD-
ROM per person in the year 2000, and almost
61 CD-ROM per person in 2007. Piling up the
imagined 404 billion CD-ROM from 2007 would
create a stack from the earth to the moon and a
quarter of this distance beyond (with 1.2 mm
thickness per CD).
Our estimate is larger than the previously
cited hardware estimate from IDC for the same
year (IDC estimates 264 exabytes of digital hard-
ware, not normalized for compression, whereas
we counted 276 optimally compressed exabytes
on digital devices, which occupy 363 exabytes
of digital hardware) (14). Although our study is
more comprehensive, we are not in a position
to fully analyze all differences because IDC’s
methodological assumptions and statistics are
based on inaccessible and proprietary company Fig. 5. World’s technological installed capacity to compute information on general-purpose computers,
sources. in MIPS (table SA3) (16).

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The inventories of Figs. 3 and 4 account for optimally compressed zettabytes in 2007. Cable lion Internet subscriptions). Nevertheless, the fixed-
only those bits that are actually communicated. In and satellite TV steadily gained importance, but line phone is still the solution of choice for voice
the case of telecommunication, the sum of the analog, “over-the-air” terrestrial television still communication (1.5% of the total). The mobile
effective usages of all users is quite similar to the dominated the evolutionary trajectory. Digital phone network became increasingly dominated
total installed capacity (any difference represents satellite television led the pack into the digital by data traffic in 2007 (1.1% for mobile data
an over- or future investment). This is because age, receiving 50% of all digital broadcast signals versus 0.8% for mobile voice).
most backbone networks are shared and only in 2007. Only a quarter of all broadcasting in- When compared with broadcasting, telecom-
used sporadically by an individual user. If all formation was in digital format in 2007. The share munications makes up a modest but rapidly grow-
users demanded their promised bandwidth simul- of radio declined gradually from 7.2% in 1986 ing part of the global communications landscape
taneously, the network would collapse. This is to 2.2% in 2007. (3.3% of the sum in 2007, up from 0.07% in
not the case for individual broadcast subscribers, Figure 4 presents effective capacity of the 1986). Although there are only 8% more broad-
who could continuously receive incoming infor- three most common bidirectional analog tele- cast devices in the world than telecommunication
mation. To meaningfully compare the carrying communication technologies and their four most equipment (6.66 billion versus 6.15 billion in
capacities of each, we applied effective consump- prominent digital heirs. The 281 petabytes of op- 2007), the average broadcasting device commu-
tion rates to the installed capacity of broadcasting timally compressed information from 1986 were nicates 27 times more information per day than
(calling it the effective capacity). This reduced overwhelmingly dominated by fixed line teleph- the average telecommunications gadget. This re-
the installed capacity by a stable factor (by 9 in ony, whereas postal letters contributed only 0.34%. sult might be unexpected, especially considering
1986, 9.1 in 1993, 8.7 in 2000, and 8.4 in 2007), The year 1993 was characterized by the digitiza- the omnipresence of the Internet, but can be un-
implying an average individual broadcast con- tion of the fixed phone network (471 optimally derstood when considering that an average Inter-
sumption of roughly 2 hours and 45 min per 24 compressed petabytes). We estimate the year net subscription effectively uses its full bandwidth
hours. It did not notably change the relative 1990 to be the turning point from analog to dig- for only around 9 min per day (during an average
distribution of the diverse technologies (Fig. 3). ital supremacy. The Internet revolution began 1 hour and 36 min daily session).
Figure 3 displays the capacity of six analog shortly after the year 2000. In only 7 years, the Computation. From a theoretical standpoint,
and five digital broadcast technologies, including introduction of broadband Internet effectively mul- a “computation” is the repeated transmission of
newspapers and personal navigation devices [glob- tiplied the world’s telecommunication capacity information through space (communication) and
al postioning system (GPS)]. In 1986, the world’s by a factor of 29, from 2.2 optimally compressed time (storage), guided by an algorithmic pro-
technological receivers picked up around 432 exabytes in 2000 to 65 in 2007. The most wide- cedure (31). The problem is that the applied
exabytes of optimally compressed information, spread telecommunication technology was the algorithmic procedure influences the overall per-
715 optimally compressed exabytes in 1993, 1.2 mobile phone, with 3.4 billion devices in 2007 formance of a computer, both in terms of hard-
optimally compressed zettabytes in 2000, and 1.9 (versus 1.2 billion fixed-line phones and 0.6 bil- ware design and in terms of the contributions of
software. As a result, the theoretical, methodo-
logical, and statistical bases for our estimates for
Fig. 6. Annual growth of computation are less solid than the ones for stor-
installed general-purpose age and communication. In contrast to Shannon’s
computational capacity as bit (29, 30), there is no generally accepted theory
percentage of all previous that provides us with an ultimate performance
computations since 1977 measure for computers. There are several ways to
(year t / S[1977, year measure computational hardware performance.
t – 1]) (table SA2) (16).
We chose MIPS as our hardware performance
metric, which was imposed on us by the reality of
available statistics. Regarding the contributions
of software, it would theoretically be possible to
normalize the resulting hardware capacity for
algorithmic efficiency (such as measured with
O-notation) (32). This would recognize the con-
Table 1. Evolution of the world’s capacity to store, communicate, and compute information, absolute per
stant progress of algorithms, which continuously
capita, CARG, and percentage in digital format (tables SA1 to SA3 and SA5) (16).
make more efficient use of existing hardware.
1986 1993 2000 2007 CAGR 1986–2007 However, the weighted contribution of each al-
gorithm would require statistics on respective exe-
MB optimal compression
Storage 539 2,866 8,988 44,716 23% cution intensities of diverse algorithms on different
per capita (installed capacity)
computational devices. We are not aware of such
Percent digital 0.8% 3% 25% 94%
statistics. As a result of these limitations, our es-
MB optimal compression
timates refer to the installed hardware capacity of
Broadcast per capita per day 241 356 520 784 6%
computers.
(effective capacity)
We distinguished between two broad groups
Percent digital 0.0% 0.0% 7.3% 25%
of computers. The first group includes all com-
MB optimal compression
puters whose functionality is directly guided by
Telecom per capita per day 0.16 0.23 1.01 27 28%
their human users. We call this group “general-
(effective capacity)
purpose computers” and include six technolog-
Percent digital 19.8% 68.5% 97.7% 99.9%
ical families (Fig. 5). The second group carries
General-purpose MIPS per capita
0.06 0.8 48 968 58% out automated computations that are incidental to
computation (installed capacity)
the primary task, such as in electronic appliances
Sample of
MIPS per capita or visual interfaces. The user may have a range of
application-specific 0.09 3.3 239 28,620 83%
(installed capacity) predefined choices regarding their functionality
computation
but cannot change the automated logic of these

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embedded systems. We call this group “application- nals (including CD, DVD, and PVR devices; cam- relatively stable rate of change (CAGRs of 5.7%,
specific computers.” eras and camcorders; modems and setup boxes; 5.6%, and 6.1% for 1986–1993, 1993–2000, and
Although general-purpose computers are also GPS; portable media; printer and fax; radio; and 2000–2007, respectively) (Table 1).
equipped with application-specific parts (for ex- fixed-line and mobile phones); microcontrollers The growth rates also allow us to look at the
ample, mobile phones come with digital signal (MCUs) (which regulate electronics and appli- application of Moore’s laws (34) for the techno-
processors, and PCs contain microcontroller units), ances); and graphic processing units (GPUs) (an logical information processing capacity of human-
we only include the capacity of humanly guid- increasingly powerful microprocessor for visual kind. Machines’ application-specific capacity to
able microprocessors in the respective inventory. displays). Although microcontrollers dominated compute information per capita has roughly dou-
The calculator laid the cornerstone for modern our sample of application-specific computing sup- bled every 14 months over the past decades in our
microprocessors and was still the dominant way port in 1986 (90% of the 4.3 × 108 application- sample, whereas the per capita capacity of the
to compute information in 1986 (41% of 3.0 × 108 specific MIPS from our sample), graphic processing world’s general-purpose computers has doubled
general-purpose MIPS). The landscape changed units clearly made up the lion’s share in 2007 every 18 months. The global telecommunication
quickly during the early 1990s as personal com- (97% of 1.9 × 1014 MIPS). capacity per capita doubled every 34 months,
puters and servers and mainframe computers Comparisons and growth rates. The world’s whereas the world’s storage capacity per capita re-
pushed the evolutionary trajectory to 4.4 × 109 technological capacity to compute information has quired roughly 40 months. Per capita broadcast
MIPS. The personal computer extended its by far experienced the highest growth (Table 1). information has doubled roughly every 12.3 years.
dominance during the year 2000 (86% of a total The per capita capacity of our sample of application- Of course, such averages disguise the varying
of 2.9 1011 MIPS), to be rivaled in 2007 by specific machine mediators grew with a compound nature of technological innovation avenues (35).
videogame consoles (1.6 × 1012 MIPS, or 25% of annual growth rate (CAGR) of 83% between 1986 Perspectives. To put our findings in perspec-
the total of 6.4 × 1012 MIPS) and increasingly and 2007, and humanly guided general-purpose tive, the 6.4 × 1018 instructions per second that
relevant mobile phones (3.7 × 1011 MIPS, or 6% computers grew at 58% per year. The world’s humankind can carry out on its general-purpose
of the 2007 total). Nowadays, clusters of video- technological capacity to telecommunicate only computers in 2007 are in the same ballpark area
game consoles are occasionally used as super- grew half as fast (CAGR of 28%). This might as the maximum number of nerve impulses exe-
computer substitutes for scientific purposes and seem a little surprising because the advancement cuted by one human brain per second (1017) (36).
other data-intensive computational tasks (33). of telecommunications, and especially the Inter- The 2.4 × 1021 bits stored by humanity in all of its
The relatively small role of supercomputers (less net, is often celebrated as the epitome of the dig- technological devices in 2007 is approaching an
than 0.5% throughout) and professional servers ital revolution. The results from Table 1 challenge order of magnitude of the roughly 1023 bits stored
and mainframes might come as a surprise. It can this idea and move the world’s ability to compute in the DNA of a human adult (37), but it is still
partially be explained by the fact that the in- information into the spotlight. The storage of minuscule as compared with the 1090 bits stored
ventory of Fig. 5 presents the installed capacity, information in vast technological memories has in the observable universe (38). However, in con-
independent of effective usage rates. We also car- experienced a growth rate almost similar to tele- trast to natural information processing, the world’s
ried out some estimations on the basis of the communication (CAGR of 23% per capita over technological information processing capacities
effective gross usage of the computers, which con- two decades). The lower growth rate results from are quickly growing at clearly exponential rates.
siders the time users interact with computers (not the relatively high base level provided by preva-
the net computational time). As a result, we get lent analog storage devices. The main character-
between 5.8 and 9.1% of the installed capacity istic of the storage trajectory is the digitalization References and Notes
(table SA4) (16). With this setup, the share of of previously analog information (from 0.8% dig- 1. M. Castells, End of Millennium, The Information Age:
Economy, Society and Culture, vol. III (Wiley-Blackwell,
servers and mainframes grew to 89% in 1986 and ital in 1986 to 94% in 2007). The global capacity Malden, MA, 2000).
11% in 2007, and supercomputers contributed to broadcast information has experienced the least 2. D. Bell, The Coming of Post-Industrial Society: A Venture
4% to the effective capacity in 2007. progress at 6% CAGR per capita. Broadcasting is in Social Forecasting (Basic Books, New York, NY, 1973).
The data also allows us to look at respective also the only information operation that is still 3. M. U. Porat, “The Information Economy: Definition and
Measurement” (1977); available at www.eric.ed.gov/
growth rates. Until the early 1990s, the annual dominated by analog ICT. As a result, the ca- ERICWebPortal/contentdelivery/servlet/ERICServlet?
growth rate was quite stable at roughly 40% pacity to store information has grown at a much accno=ED142205.
(Fig. 6). The 1990s show outstanding growth, faster rate than that of the combined growth rate 4. Y. Masuda, The Information Society as Post-Industrial
reaching a peak of 88% in 1998. Since then, the of tele- and broadcast communication. In 1986, Society (Transaction Publishers, Piscataway, NJ, 1980).
5. C. Perez, Futures 15, 357 (1983).
technological progress has slowed. In recent times, it would have been possible to fill the global stor- 6. T. Forester, The Information Technology Revolution
every new year allows humankind to carry out age capacity with the help of all effectively used (MIT Press, Cambridge, MA, 1985).
roughly 60% of the computations that could have communication technologies in roughly 2.2 days 7. C. Freeman, F. Louçã, As Time Goes By: From the
possibly been executed by all existing general- (539/241.16). In 1993, it would have taken al- Industrial Revolutions to the Information Revolution
(Oxford Univ. Press, New York, 2002).
purpose computers before that year. most 8 days; in the year 2000, it would take
8. M. Castells, The Rise of the Network Society: The
Our inventory of application-specific compu- roughly 2.5 weeks; and in 2007, almost 8 weeks Information Age: Economy, Society, and Culture, vol. I
tations is the least complete one. The entire group would be required. (Wiley-Blackwell, Malden, MA, 2009).
of application-specific computers is very large The CAGRs represent the temporal average 9. E. Brynjolfsson, A. Saunders, Wired for Innovation:
and diverse (for example, dice cups and roulette of periods that were experiencing different pat- How Information Technology is Reshaping the Economy
(MIT Press, Cambridge, MA, 2009).
wheels are application-specific, analog, random- terns of technological change. General-purpose 10. Y. Ito, Mass Commun. Rev. Yearbook 2, 671 (1981).
number generators), and it is often not straight- computation had its peak growth around the turn 11. I. D. S. Pool, Science 221, 609 (1983).
forward to translate their performance into MIPS. of the millennia (Fig. 6). Storage capacity slowed 12. M. Lesk, “How Much Information Is There In the World?”
The main goal of our inventory of this group was down around the year 2000, but accelerated growth (1997); available at www.lesk.com/mlesk/ksg97/ksg.html.
13. P. Lyman et al., “How Much Information? 2003” (Univ.
to show that the computational hardware capacity has been occurring in recent years (CAGR of California at Berkeley, Berkeley, CA, 2003); available at
of application-specific computers is larger than 27% for 1986–1993, 18% for 1993–2000, and www2.sims.berkeley.edu/research/projects/how-much-
the computational capacity of general-purpose 26% for 2000–2007) (Table 1). The introduction info-2003/.
computers (table SA3) (16). To achieve this, we of broadband has led to a continuous acceleration 14. J. Gantz et al., “The Diverse and Exploding Digital Universe:
An Updated Forecast of Worldwide Information Growth
focused on a sample that includes three promi- of telecommunication (CAGR of 6% for 1986– Through 2011” (IDC sponsored by EMC, Framingham,
nent groups: digital signal processors (DSPs), 1993, 23% for 1993–2000, and 60% for 2000– 2008); available at www.emc.com/leadership/digital-
which translate between analog and digital sig- 2007) (Table 1), whereas broadcasting had a universe/expanding-digital-universe.htm.

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15. R. Bohn, J. Short, “How Much Information? 2009 Report 26. T. Coughlin, “Digital Storage Technology Newsletters” 37. This is considering a quaternary DNA alphabet, in
on American Consumers” (Global Information Industry (Coughlin Associates, Atascadero, CA, 2007); available at which each base pair can store 4 bits × 3 billion
Center of University of California, San Diego, San Diego, CA, www.tomcoughlin.com/. DNA base pairs per human cell × 60 trillion cells
2009); available at http://hmi.ucsd.edu/howmuchinfo.php. 27. Global Technology Team, “Technology Q1 2006 Global per adult human. Because base pair couples are
16. Materials and methods are available as supporting Technology Data Book” (Morgan Stanley, New York, determined, the 4 bits can be compressed to 2 bits,
material on Science Online. 2006); available at www.morganstanley.com/institutional/ which can optimally be compressed to 1.73 inside
17. International Telecommunications Union (ITU), “World techresearch/pdfs/global_techdatabook0306.pdf. one cell (40).
Telecommunication/ICT Indicators Database” (ITU, Geneva, 28. International Data Corporation (IDC), IDC Media Center 38. S. Lloyd, Phys. Rev. Lett. 88, 237901 (2002).
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Berne, Switzerland, 2007); available at www.upu.int/en/ (Wiley-Interscience, Hoboken, NJ, 2006). ECLAC (in Chile) for its support; T. Coughlin, J. McCallum,
resources/postal-statistics/. 31. A. M. Turing, Proc. London Math. Soc. s2, 230 D. Franz, M. Gonzalez, C. Vasquez, L. Adleman, M. Castells,
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“The Recording Industry World Sales 1995–2004”; available 32. T. Cormen, C. Leiserson, R. Rivest, C. Stein, Introduction and ITU (International Telecommunications Union); as
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Releases” (2007); available at www.jria.org/english.html. Supercomputer with Eight PlayStation 3s”; available
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2005); available at www.disktrend.com/. of computer performance by counting the numbers Figs. A1 to E12
24. R. Longbottom, “Computer Speed Claims 1980 to 1996” of transistors on an integrated circuit, which has Tables SA1 to SE24
(Roy Longbottom’s PC Benchmark collection, 2006); approximately doubled every 2 years since the References and Notes
available at www.roylongbottom.org.uk/mips.htm. 1960s (39).
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V. G. Oklobdzija, Ed. (CRC, Boca Raton, FL, 2002), 36. This is assuming 100 billion neurons × 1000 connections Published online 10 February 2011;
pp. 136–153. per neuron × maximum 1000 nerve impulses per second. 10.1126/science.1200970

Chronic Mucocutaneous Candidiasis (1). CMC disease (CMCD), the molecular and
cellular basis of which is unknown, consists of
CMC in the absence of other overt infectious
in Humans with Inborn Errors of or autoimmune signs (1). CMCD was initially
thought to be benign, until squamous cell carci-
Interleukin-17 Immunity noma (9) and cerebral aneurysms (10) were re-
ported. First described in 1967 in sporadic cases
(11), familial CMC segregating as autosomal dom-
Anne Puel,1*‡ Sophie Cypowyj,2* Jacinta Bustamante,1 Jill F. Wright,3 Luyan Liu,1 inant (AD) (12) and autosomal recessive (AR)
Hye Kyung Lim,2 Mélanie Migaud,1 Laura Israel,1 Maya Chrabieh,1 Magali Audry,2 traits (13) was soon reported. We thus searched for
Matthew Gumbleton,4 Antoine Toulon,5 Christine Bodemer,5 Jamila El-Baghdadi,6 the genetic basis of CMCD, testing the hypoth-
Matthew Whitters,3 Theresa Paradis,3 Jonathan Brooks,3 Mary Collins,3 esis that CMCD may be caused by inborn errors
Neil M. Wolfman,3 Saleh Al-Muhsen,7 Miguel Galicchio,8 Laurent Abel,1,2† of IL-17A, IL-17F, or IL-22 immunity (1, 14).
Capucine Picard,1,9,10† Jean-Laurent Casanova1,2,7,10‡ Autosomal recessive IL-17RA deficiency. We
first investigated a French child born to first-
Chronic mucocutaneous candidiasis disease (CMCD) is characterized by recurrent or persistent cousin parents of Moroccan descent (Fig. 1A)
infections of the skin, nails, and oral and genital mucosae caused by Candida albicans and, to [report S1 (15)]. He presented with C. albicans
a lesser extent, Staphylococcus aureus, in patients with no other infectious or autoimmune dermatitis during the neonatal period and dis-
manifestations. We report two genetic etiologies of CMCD: autosomal recessive deficiency in the
cytokine receptor, interleukin-17 receptor A (IL-17RA), and autosomal dominant deficiency of 1
the cytokine interleukin-17F (IL-17F). IL-17RA deficiency is complete, abolishing cellular responses Laboratory of Human Genetics of Infectious Diseases, Necker
Branch, Institut National de la Santé et de la Recherche
to IL-17A and IL-17F homo- and heterodimers. By contrast, IL-17F deficiency is partial, with mutant Médicale, U980, and University Paris Descartes, Necker
IL-17F–containing homo- and heterodimers displaying impaired, but not abolished, activity. Medical School, 75015 Paris, France. 2St. Giles Laboratory of
These experiments of nature indicate that human IL-17A and IL-17F are essential for Human Genetics of Infectious Diseases, Rockefeller Branch,
mucocutaneous immunity against C. albicans, but otherwise largely redundant. The Rockefeller University, New York, NY 10065, USA. 3In-
flammation and Immunology, Pfizer Research, Cambridge,
MA 02140, USA. 4SUNY Upstate Medical University, Syracuse,
NY 13210, USA. 5Dermatology Unit, Necker Hospital, 75015
hronic mucocutaneous candidiasis (CMC) interleukin-12 receptor b1 (IL-12Rb1) deficiency

C is characterized by infections of the skin,


nails, and oral and genital mucosae with
Candida albicans, which is commensal in healthy
and mycobacterial disease (2) and in a family
with caspase recruitment domain 9 (CARD9) de-
ficiency with systemic candidiasis and peripheral
Paris, France. 6Unit of Genetics, Military Hospital of Instruc-
tion Mohamed V, Rabat 10000, Morocco. 7Prince Naif Center
for Immunology Research, Department of Pediatrics, College
of Medicine, King Saud University, Riyadh 11461, Saudi
Arabia. 8 Victor J. Vilela Children’s Hospital, Rosario, Santa Fe
individuals (1). In patients with inherited or ac- dermatophytosis (6), CMC and low proportions of 2000, Argentina. 9Center for the Study of Primary Immuno-
quired T cell immunodeficiencies, CMC is as- IL-17A–producing T cells were also documented. deficiencies, Necker Hospital, 75015 Paris, France. 10Pediatric
sociated with various infectious diseases (1). In Finally, CMC is the only infection of patients with Hematology-Immunology Unit, Necker Hospital, Paris 75015,
patients with STAT3 deficiency and a lack of autoimmune regulator (AIRE) deficiency, who France.
interleukin-17A (IL-17A)– and IL-22–producing have neutralizing autoantibodies against IL-17A, *These authors contributed equally to this work.
†These authors contributed equally to this work.
T cells (2–5), CMC is associated with severe IL-17F, and/or IL-22 (7, 8). These data suggest ‡To whom correspondence should be addressed. E-mail:
cutaneous and pulmonary staphylococcal infec- that human IL-17A, IL-17F, and/or IL-22 are in- jean-laurent.casanova@rockefeller.edu (J.-L.C.); anne.
tions (1). In some patients with IL-12p40 or volved in mucocutaneous immunity to C. albicans puel@inserm.fr (A.P.)

WorldMags www.sciencemag.org SCIENCE VOL 332 1 APRIL 2011 65


RESEARCH ARTICLES
played Staphylococcus aureus dermatitis at 5 Transfection of the patient’s fibroblasts with bers of the kindred with CMCD; we were unable
months of age. Known causes of CMC were wild-type (WT) IL17RA, but not with a mock to genotype the fifth patient (III.1 in Fig. 3A), who
excluded clinically and genetically, and the lack vector, restored IL-17RA expression and the re- died at 6 years of age from complications of the
of any phenotype other than CMC led to a di- sponse to IL-17 cytokines (Fig. 2, D to F). By disease. The mutant allele was found in only two
agnosis of AR CMCD. We sequenced the candi- contrast, IL-6 production by NEMO-deficient apparently healthy family members, aged 9 months
date genes encoding IL-22, IL-22RA1, IL-10RB, cells was not rescued by transfection with (III.3 in Fig. 3A) and 21 years (II.8 in Fig. 3A),
IL-17A, IL-17F, IL-17RA, and IL-17RC (16–18). IL17RA (fig. S4B). Thus, the patient with CMCD which suggested incomplete clinical penetrance.
IL-22 binds as a monomer to its receptor, com- that we studied displayed AR, complete IL-17RA We did not detect IL-17F–expressing T cells in
posed of IL-22RA1 and IL-10RB, whereas IL-17A deficiency, and a lack of cellular responses to at controls by flow cytometry, but the patients tested
and IL-17F can form homo- or heterodimers least three IL-17 cytokine dimers—IL-17A, displayed normal proportions of IL-17A– and
that signal via a receptor comprising IL-17RA IL-17F, and IL-17A–IL-17F—in fibroblasts IL-22–expressing T cells, and their PBMCs se-
and IL-17RC chains. The child was found to be and leukocytes. creted normal amounts of cytokines, as measured
homozygous for the c.850C>T nonsense muta- Autosomal dominant IL-17F deficiency. We by Bioplex (fig. S7, A and B).
tion (c.850C>T/c.850C>T), which replaces the then investigated a multiplex family from Argen- We investigated the possible deleterious ef-
glutamine codon in position 284 with a stop co- tina, with AD inheritance of CMCD (Fig. 3A) [re- fects of the S65L mutation by producing the
don (Q284X/Q284X) in the IL17RA gene (19) port S2 (15)]. The IL22, IL22RA, IL10RB, IL17RA, mutant IL-17F protein in human embryonic kid-
(Fig. 1B). This premature stop codon is located in IL17RC, and IL17A genes contained no muta- ney (HEK) 293 cells. The mutation did not seem
the part of the gene encoding the extracellular tions, but a heterozygous missense mutation was to affect production of the monomeric protein or
domain of IL-17RA, upstream from the trans- found in the IL17F gene of the index case. This the formation of IL-17F homodimers (mutant-
membrane domain sequence (Fig. 1C). No mu- mutation, c.284C>T, replaced the serine residue mutant and wild-type–mutant) or heterodimers
tations were found elsewhere in IL17RA or in in position 65 of the mature protein with a leucine with IL-17A (fig. S8). The mutant-containing di-
any of the other six genes sequenced. The parents residue (S65L) (Fig. 3, B and C). The Ser65 res- mers seemed to bind normally to homodimeric
and siblings of this child are healthy and het- idue is conserved across mammalian species (fig. IL-17 receptors (IL-17RA and IL-17RC), as shown
erozygous for the mutant allele, consistent with S5). Moreover, the sequencing of 1074 control by surface plasmon resonance (table S1 and fig.
AR inheritance for this trait. The mutant allele individuals from the CEPH-HGD panel ruled out S9). However, the mutant proteins did not bind
was not found in 1065 healthy controls from 52 the possibility that this mutation was an irrelevant IL-17RA on fibroblasts, as shown by flow cytom-
ethnic groups from the Centre d'Etude du Poly- polymorphism. Computational analysis showed etry, with IL-17RA–deficient cells as controls
morphisme Humain–Human Genome Diversity that Ser65 lies in the cavity of the protein, which is (confirming that their lack of IL-17RA expression
Cell Line Panel CEPH-HGDP, 100 French con- thought to be involved in cytokine-to-receptor prevented cytokine binding) (figs. S10 and S11).
trols, and 70 Moroccan controls of Berber descent, binding (Fig. 3C) (21). No other IL17F varia- Accordingly, when control fibroblasts (Fig. 4, A
which ruled out an irrelevant polymorphism and tions were found in the index case, including the and B) and keratinocytes (fig. S12, A and B)
suggested that the mutation may define a rare AR IL17F g.7488T>C (rs763780) polymorphism, in were stimulated with mutant S65L IL-17F ho-
CMCD-causing allele. which an arginine residue replaced a histidine in modimers, they displayed much weaker IL-6
The IL-17RA protein was not detected on the position 161 of the protein (H161R), a mutation and GRO-a induction than observed with WT
surface of fibroblasts, peripheral blood mono- previously thought to be loss-of-function (22). By IL-17F homodimers (IL-17WT), IL-17A homo-
nuclear cells (PBMCs), or, more specifically, CD4+ contrast, we found that the H161R allele encoded dimers, or IL-17A–IL-17FWT heterodimers (20).
T cells, CD8+ T cells, and monocytes from the an IL-17F protein able to stimulate murine lung Moreover, control PBMCs showed impaired in-
patient, as shown by flow cytometry with two spe- epithelial cells (MLEs) (fig. S6). Heterozygosity duction of several cytokines when stimulated
cific antibodies against the extracellular domain for the S65L allele was found in all tested mem- with S65L IL-17F homodimers compared with
(Fig. 2A and fig. S1). The absence of IL-17RA
had no impact on the expression of IL-17RC,
which was normal on the patient’s monocytes
(the only leukocyte subset expressing IL-17RC
in controls) and fibroblasts (figs. S1 and S2).
Likewise, IL-22RA1 was normally expressed on
the patient’s fibroblasts (fig. S2). The patient also
had a normal proportion of circulating IL-17A–
and IL-22–producing T cells (fig. S3). We inves-
tigated whether the lack of IL-17RA expression
had any functional consequences for the response
to IL-17 cytokines, by testing the responses of the
patient’s fibroblasts to various concentrations of
recombinant IL-17A and IL-17F homodimers
and to IL-17A–IL-17F heterodimers (17, 18). Like
nuclear factor-kB essential modulator (NEMO)–
deficient fibroblasts, which have impaired NF-kB
activity, and unlike fibroblasts from a healthy
control, the patient’s fibroblasts did not respond Fig. 1. A kindred with autosomal recessive IL-17RA deficiency.
to any of the three IL-17 cytokines, in terms of (A) Pedigree of the family established by IL-17RA genotyping. The
IL-6 and growth-regulated oncogene-a (GRO-a) proband is indicated by an arrow. E? indicates individuals whose
induction (20), as assessed by enzyme-linked genetic status could not be evaluated. (B) IL17RA DNA sequence
immunosorbent assay (ELISA) on supernatants electrophoregrams for a control and the patient. (C) Schematic diagram of the IL-17RA protein with the
(Fig. 2, B and C). Moreover, the patient’s PBMCs signal sequence (SS), extracellular (EC), transmembrane (TM), intracellular (IC), and SEFIR (expression
did not respond above baseline to IL-17A or similar to fibroblast growth factor–IL-17R) domains and the position within the extracellular domain
IL-17F for any of the cytokines tested (fig. S4A). affected by the mutation.

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66 1 APRIL 2011 VOL 332 SCIENCE www.sciencemag.org
RESEARCH ARTICLES
WT IL-17F homodimers (fig. S12C). These allele, which impairs the receptor binding and IL-17F are also vulnerable (27). IL-17A or IL-17F
data suggest that the IL17F S65L allele is se- bioactivity of both IL-17F homodimers and IL- alone are not required for peripheral immunity
verely hypomorphic (Fig. 4, A and B, and fig. 17A–IL-17F heterodimers. to S. aureus, but mice deficient for both IL-17A
S12, A and B). Furthermore, when the S65L Concluding remarks. IL-17RA and IL-17F and IL-17F display an impaired peripheral im-
mutant IL-17F formed a heterodimer with either deficiencies underlying mucocutaneous disease munity to S. aureus (28). Somewhat at odds with
IL-17FWT or IL-17A, the induction of IL-6 and caused by C. albicans and, to a lesser extent, our observations, IL-17A is also required for sys-
GRO-a was severely impaired in control fibro- S. aureus are consistent with the mouse model temic immunity to C. albicans (29) and S. aureus
blasts (Fig. 4, A and B) and keratinocytes (fig. (23). IL-17RA– and IL-17RC–deficient mice (30). Moreover, mice with IL-17RA, IL-17RC,
S12, A and B), which indicated a dominant- were more susceptible to oropharyngeal candi- IL-17A, or IL-17F deficiency are vulnerable to
negative effect of this allele. Finally, as predicted diasis (24, 25) and IL-17RA–deficient mice to multiple infections at various anatomical sites
by the lack of binding of mutant cytokine di- cutaneous staphylococcal disease (26). IL-17A– (17, 23). Overall, our report indicates that hu-
mers to their receptor (fig. S11), these dimers deficient mice also display impaired clearance of man IL-17A and IL-17F are essential for pro-
did not compete with WT dimers (fig. S13, A to C. albicans skin infection (27). IL-17F–deficient tective immunity to C. albicans and, to a lesser
D). Thus, the AD CMCD in this kindred results mice have not yet been tested, but IL-23–deficient extent, S. aureus in the nails, skin, and oral and
from a hypomorphic, dominant-negative IL17F mice with impaired expression of IL-17A and genital mucosae, but otherwise redundant. We

Fibroblasts Transfected fibroblasts


A 60
Control
60
Patient D 50 Empty vector
50
IL-17RA WT

Cell counts
Cell counts

0 0
0 1 2 3 4 0 1 2 3 4
10 10 10 10 10 10 10 10 10 10 0 0
0 1 2 3 4 0 1 2 3 4
10 10 10 10 10 10 10 10 10 10
Non adherent PBMCs
IL-17RA
80
Control
80
Patient
E 0.25
Empty vector
IL-17RA WT
0.20
IL-6 (ng/ml)

0.15

0.10

0 0 0.05
0 1 2 3 4 0 1 2 3 4
10 10 10 10 10 10 10 10 10 10

B IL-17RA 0
NS IL-17A/ IL-17F/ IL-17A/
50.0 IL-17A IL-17F IL-17F
Control
F 0.80
Patient Empty vector
40.0 IL-17RA WT
NEMO-/-
IL-6 (ng/ml)

GRO-α (ng/ml)

0.60
30.0

2.0 0.40

1.0
0.20
UD.
UD.

UD.

UD.

UD.

0
NS IL-17A/ IL-17F/ IL-17A/ IL-1β
C IL-17A IL-17F IL-17F 0
60.0 NS IL-17A/ IL-17F/ IL-17A/
Control IL-17A IL-17F IL-17F
Patient
50.0 NEMO-/-
Fig. 2. Production and function of the mutant IL-17RA chain. (A) IL-17RA
GRO-α (ng/ml)

40.0
expression in SV40-immortalized fibroblasts (top) and nonadherent PBMCs (bot-
tom) from a control and the patient, as detected by flow cytometry. Isotype
control, black; IL-17RA antibody, gray. (B) IL-6 and (C) GRO-a production by
2.0
SV40-immortalized fibroblasts from a control, the patient, and NEMO-deficient
cells after 24 hours of stimulation with IL-17A, IL-17F, and IL-17A–IL-17F. Means T
1.0 SD (error bars) of three independent experiments, as detected by ELISA. UD,
undetectable. (D) IL-17RA expression in SV40-immortalized fibroblasts from the
0 patient, transfected with the empty pORF9mcs plasmid (left) or the pORF9-hIL-
NS IL-17A/ IL-17F/ IL-17A/ IL-1β
IL-17A IL-17F IL-17F 17RA plasmid (right), as detected by flow cytometry. Isotype control, black; IL17RA
antibody, gray. (E) IL-6 and (F) GRO-a production by SV40-immortalized fibro-
blasts from the patient, transfected with the empty pORF9mcs plasmid (white) or the pORF9-hIL17RA plasmid (gray), after 24 hours of stimulation with IL-17A,
IL-17F, and IL-17A–IL-17F. Means T SD (error bars) of three independent experiments, as detected by ELISA.

WorldMags www.sciencemag.org SCIENCE VOL 332 1 APRIL 2011 67


RESEARCH ARTICLES
References and Notes
1. A. Puel et al., Curr. Opin. Immunol. 22, 467 (2010).
2. L. de Beaucoudrey et al., J. Exp. Med. 205, 1543
(2008).
3. C. S. Ma et al., J. Exp. Med. 205, 1551 (2008).
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6. E. O. Glocker et al., N. Engl. J. Med. 361, 1727
(2009).
7. K. Kisand et al., J. Exp. Med. 207, 299 (2010).
8. A. Puel et al., J. Exp. Med. 207, 291 (2010).
9. D. M. Williamson, Br. J. Dermatol. 81, 125 (1969).
10. D. Leroy, A. Dompmartin, J. P. Houtteville, J. Theron,
Dermatologica 178, 43 (1989).
11. R. A. Chilgren, P. G. Quie, H. J. Meuwissen, R. Hong,
Lancet 290, 688 (1967).
12. L. Canales, R. O. Middlemas 3rd, J. M. Louro, M. A. South,
Lancet 294, 567 (1969).
13. R. S. Wells, J. M. Higgs, A. Macdonald, H. Valdimarsson,
P. J. Holt, J. Med. Genet. 9, 302 (1972).
14. J. L. Casanova, L. Abel, Science 317, 617 (2007).
15. Materials and methods are available as supporting
material on Science Online.
16. K. Wolk, E. Witte, K. Witte, K. Warszawska, R. Sabat,
Semin. Immunopathol. 32, 17 (2010).
17. T. Korn, E. Bettelli, M. Oukka, V. K. Kuchroo, Annu. Rev.
Immunol. 27, 485 (2009).
18. S. L. Gaffen, Nat. Rev. Immunol. 9, 556 (2009).
19. Single-letter abbreviations for the amino acid residues
are as follows: A, Ala; C, Cys; D, Asp; E, Glu; F, Phe;
G, Gly; H, His; I, Ile; K, Lys; L, Leu; M, Met; N, Asn;
P, Pro; Q, Gln; R, Arg; S, Ser; T, Thr; V, Val;
W, Trp; Y, Tyr; and X, stop.
20. J. F. Wright et al., J. Immunol. 181, 2799 (2008).
21. S. G. Hymowitz et al., EMBO J. 20, 5332 (2001).
22. M. Kawaguchi et al., J. Allergy Clin. Immunol. 117, 795
(2006).
23. S. A. Khader, S. L. Gaffen, J. K. Kolls, Mucosal Immunol.
2, 403 (2009).
24. H. R. Conti et al., J. Exp. Med. 206, 299 (2009).
25. A. W. Ho et al., J. Immunol. 185, 1063 (2010).
26. J. S. Cho et al., J. Clin. Invest. 120, 1762 (2010).
27. S. Kagami, H. L. Rizzo, S. E. Kurtz, L. S. Miller,
Fig. 3. A kindred with autosomal dominant IL-17F deficiency. (A) Family pedigree, with allele seg- A. Blauvelt, J. Immunol. 185, 5453 (2010).
regation. The patients, shown in black, are all heterozygous for the mutation, as is II.8, who is 28. H. Ishigame et al., Immunity 30, 108 (2009).
asymptomatic. The proband is indicated by an arrow. E? indicates individuals whose genetic status could 29. S. Saijo et al., Immunity 32, 681 (2010).
not be evaluated. III.3 is a 9-month-old baby, also heterozygous for the mutation and currently 30. L. Henningsson et al., Infect. Immun. 78, 3783
asymptomatic. All other family members are healthy and WT for IL17F and are shown in white. (B) (2010).
Heterozygous c.284C>T mutation in the patients. IL17F DNA sequence electrophoregrams of a control 31. A. Alcaïs et al., Ann. N. Y. Acad. Sci. 1214, 18
(2010).
and the patient III.2. (C) Ribbon trace of the IL-17F dimer. Beta strands are labeled. Sulfur atoms are 32. W. Hueber et al.; Psoriasis Study Group; Rheumatoid
shown in yellow. The position of the cavity that binds to the receptor is indicated by a black circle. Arthritis Study Group; Uveitis Study Group, Sci. Transl.
Med. 2, 52ra72 (2010).
A B 33. We thank the patients, their families, and their clinicians.
50 60 We also thank all members of the laboratory for helpful
1 1
10 discussions and T. Kochetkov for keratinocyte culture.
10
40 100 100 This work was supported by institutional funding from
GRO-α (ng/ml)
IL-6 (ng/ml)

INSERM, University Paris Descartes, the Rockefeller


40
30 University, the Rockefeller University CTSA grant number
5UL1RR024143-04, the St. Giles Foundation, and the
Candidoser association awarded to J.-L.C. Genomic DNA
20
20 sequences of the mutations IL-17RA (JF305973) and
IL-17F (JF305974) can be found in GenBank. The
10
following reagents are available under a Materials
Transfer Agreement: human IL-17A homodimer
0 0
(– mutation) purified protein, human IL-17F homodimer
IL-17Fm
IL-17Fm

NS
NS

IL-17Fm
IL-17Fm

IL-17Fm/
IL-17Fm
IL-17F/
IL-17F
IL-17A/
IL-17A

IL-17A/
IL-17Fm/
IL-17Fm

IL-17A/
IL-17A

IL-17F/
IL-17F
IL-17F

IL-17A/
IL-17A/

IL-17A/
IL-17F/

IL-17F
IL-17F/

(+/− mutation) purified protein, human IL-17A–IL-17F


heterodimer (+/− mutation) purified protein, and
antibody against human IL-17F.
Fig. 4. Function of the mutant IL-17F protein. (A) Production of IL-6 and (B) GRO-a by control SV40
fibroblasts in response to increasing doses (ng/ml) of IL-17A, IL-17FWT, mutant IL-17F (IL-17FS65L), Supporting Online Material
IL-17FWT–IL-17FS65L homodimers and of IL-17A–IL-17FWT and IL-17A–IL-17FS65L heterodimers for www.sciencemag.org/cgi/content/full/science.1200439/DC1
Materials and Methods
24 hours. Means T SD (error bars) of three independent experiments, as detected by ELISA. Figs. S1 to S13
Table S1
cannot exclude the possibility that other infec- cutaneous immunity to C. albicans (14, 31). Pa- References
tions may occur in patients with inborn errors of tients receiving IL-17–blocking agents should be 15 November 2010; accepted 7 February 2011
IL-17 immunity. In any event, in natura, inborn carefully monitored, at least for mucocutaneous Published online 24 February 2011;
errors of IL-17 immunity clearly impair muco- infections (32). 10.1126/science.1200439

WorldMags
68 1 APRIL 2011 VOL 332 SCIENCE www.sciencemag.org
REPORTS
350- to 610-km, 70°-inclination orbit as part of
the Russian Resurs-DK1 spacecraft (14).
PAMELA Measurements of Our results are consistent with those of other
experiments (Fig. 1), considering the statistical
Cosmic-Ray Proton and Helium Spectra and systematic uncertainties of the various ex-
periments. There are differences at low energies
(< 30 GeV) caused by solar-modulation effects
O. Adriani,1,2 G. C. Barbarino,3,4 G. A. Bazilevskaya,5 R. Bellotti,6,7 M. Boezio,8 [PAMELA was operating during a period of min-
E. A. Bogomolov,9 L. Bonechi,1,2 M. Bongi,2 V. Bonvicini,8 S. Borisov,10,11,12 S. Bottai,2 imum solar activity with a solar-modulation pa-
A. Bruno,6,7 F. Cafagna,7 D. Campana,4 R. Carbone,4,11 P. Carlson,13 M. Casolino,10 rameter (F) of 450 to 550 MV in the spherical
G. Castellini,14 L. Consiglio,4 M. P. De Pascale,10,11 C. De Santis,10,11 N. De Simone,10,11 force-field approximation (15)]. PAMELA results
V. Di Felice,10 A. M. Galper,12 W. Gillard,13 L. Grishantseva,12 G. Jerse,8,15 A. V. Karelin,12 overlap with Advanced Thin Ionization Calorim-
S. V. Koldashov,12 S. Y. Krutkov,9 A. N. Kvashnin,5 A. Leonov,12 V. Malakhov,12 V. Malvezzi,10 eter (ATIC)–2 data (16) between ~200 and ~1200
L. Marcelli,10 A. G. Mayorov,12 W. Menn,16 V. V. Mikhailov,12 E. Mocchiutti,8 A. Monaco,6,7 GV, but differ both in shape and absolute normal-
N. Mori,1,2 N. Nikonov,9,10,11 G. Osteria,4 F. Palma,10,11 P. Papini,2 M. Pearce,13 ization at lower energies. The extrapolation to
P. Picozza,10,11* C. Pizzolotto,8 M. Ricci,17 S. B. Ricciarini,2 L. Rossetto,13 R. Sarkar,8 higher energy of the PAMELA fluxes suggests a
M. Simon,16 R. Sparvoli,10,11 P. Spillantini,1,2 Y. I. Stozhkov,5 A. Vacchi,8 E. Vannuccini,2 broad agreement with the results of CREAM (Cos-
G. Vasilyev,9 S. A. Voronov,12 Y. T. Yurkin,12 J. Wu,13† G. Zampa,8 N. Zampa,8 V. G. Zverev12 mic Ray Energetics and Mass Experiment) (17)
and JACEE (Japanese-American Collaborative
Protons and helium nuclei are the most abundant components of the cosmic radiation. Precise Emulsion Experiment) (18); the extrapolation of
measurements of their fluxes are needed to understand the acceleration and subsequent PAMELA helium flux is higher than the helium
propagation of cosmic rays in our Galaxy. We report precision measurements of the proton and flux measured by RUNJOB (Russia-Nipon Joint
helium spectra in the rigidity range 1 gigavolt to 1.2 teravolts performed by the satellite-borne Balloon) experiment (19).
experiment PAMELA (payload for antimatter matter exploration and light-nuclei astrophysics). To gain a better understanding of the spectra,
We find that the spectral shapes of these two species are different and cannot be described well we have analyzed our results in terms of rigidity
by a single power law. These data challenge the current paradigm of cosmic-ray acceleration in instead of kinetic energy per nucleon (Fig. 2 and
supernova remnants followed by diffusive propagation in the Galaxy. More complex processes tables S3 and S4). Two important conclusions
of acceleration and propagation of cosmic rays are required to explain the spectral structures can be drawn from the PAMELA data.
observed in our data. First, the proton and helium spectra [J(R)]
have different spectral shapes. If a single power
law, J ðRÞ ¼ AR − g (where A is the normalization
R
ince the discovery of cosmic rays, various At the end of the acceleration phase, particles

S mechanisms have been proposed to explain


the acceleration of particles to relativistic
energies and their subsequent propagation in our
are injected into the interstellar medium where
they propagate, diffusing through the turbulent
Galactic magnetic fields. Nowadays, this propa-
constant, R is rigidity, and g is the spectral index),
is fit to the data between 30 GV (above the influ-
ence of solar modulation) and 1.2 TV, the result-
Galaxy. It was pointed out long ago (1, 2) that gation is well described by solving, numerically ing spectral indices are gR30−1000 GV,p ¼ 2:820 T
supernovae fulfill the power requirement to en- (4) or analytically (5, 6), the transport equations 0:003(stat) T0:005(syst) and gR30−1000 GV,He ¼
ergize Galactic cosmic rays. Subsequently, mod- for particle diffusion in the Galaxy. The Galac- 2:732 T0:005(stat)þ0:008−0:003 (syst), which establishes
els were put forward explaining the acceleration tic magnetic fields mask the arrival direction of that there is a significant difference between the
of cosmic-ray particles via diffusive shock accel- charged particles, making the cosmic-ray flux two spectral indices in this rigidity region (stat,
eration produced by supernova shock waves prop- isotropic, although there are hints of anisotropy in statistical errors; syst, systematic errors; p, proton;
agating in the interstellar medium [see (3) for a the 10- to 100-TeV range (7). He, helium). These effects are also seen in Fig. 3
review]. Recent PAMELA ( payload for antimatter (and in table S5), where the proton-to-helium flux
matter exploration and light-nuclei astrophysics) ratio is shown as a function of rigidity. Present-
1
Department of Physics, University of Florence, I-50019 Sesto measurements of the antiparticle component of ing the results as a ratio reduces the possible impact
Fiorentino, Florence, Italy. 2Istituto Nazionale di Fisica Nucleare the cosmic radiation (8–10) have prompted a re- of systematic errors, because a number of instru-
(INFN), Sezione di Florence, I-50019 Sesto Fiorentino, Florence, evaluation of possible contributions from addi- mental effects cancel in the ratio (for example,
Italy. 3Department of Physics, University of Naples “Federico II,” tional Galactic sources, either of astrophysical the estimation of live time and the error associated
I-80126 Naples, Italy. 4INFN, Sezione di Naples, I-80126 Naples,
Italy. 5Lebedev Physical Institute, RU-119991, Moscow, Russia. [e.g., pulsars (11)] or exotic [e.g., dark matter with the alignment of the tracker and the track-
6
Department of Physics, University of Bari, I-70126 Bari, Italy. (12, 13)] origin. Detailed knowledge of cosmic- reconstruction algorithm). The proton-to-helium
7
INFN, Sezione di Bari, I-70126 Bari, Italy. 8INFN, Sezione di ray spectra is needed to: (i) identify sources and flux ratio shows a continuous and smooth de-
Trieste, I-34149 Trieste, Italy. 9Ioffe Physical Technical Institute, acceleration/propagation mechanisms of cosmic crease as the rigidity increases. The same ratio cast
RU-194021 St. Petersburg, Russia. 10INFN, Sezione di Rome
“Tor Vergata,” I-00133 Rome, Italy. 11Department of Physics,
rays; (ii) estimate the production of secondary in terms of kinetic energy per nucleon or total
University of Rome “Tor Vergata,” I-00133 Rome, Italy. 12Moscow particles, such as positrons and antiprotons, to kinetic energy exhibits more irregular behavior
Engineering and Physics Institute, RU-11540 Moscow, Russia. disentangle the secondary-particle component from (fig. S1). By applying a power-law approxima-
13
Department of Physics, Kungliga Tekniska Högskolan, and the possible exotic sources; and (iii) estimate the par- tion to the two spectra, the ratio can be used to
Oskar Klein Centre for Cosmoparticle Physics, AlbaNova Uni-
ticle flux in the geomagnetic field and in Earth’s determine the difference between the two spec-
versity Centre, SE-10691 Stockholm, Sweden. 14Istituto di Fisica
Applicata Nello Carrara, I-50019 Sesto Fiorentino, Florence, atmosphere for in-orbit dose estimations and to tral indices with a smaller associated systematic
Italy. 15Department of Physics, University of Trieste, I-34147 derive the atmospheric muon and neutrino flux, error DgR ¼ gRp − gRHe ¼ 0:101 T 0:0014 (stat) T
Trieste, Italy. 16Department of Physics, Universität Siegen, respectively. 0:0001(sys). The ratio is well described by a
D-57068 Siegen, Germany. 17INFN, Laboratori Nazionali di We present absolute cosmic-ray proton and power law down to rigidities as low as 5 GV
Frascati, Via Enrico Fermi 40, I-00044 Frascati, Italy.
helium spectra in the rigidity interval between (green line in Fig. 3). For rigidities R >> F, the
*To whom correspondence should be addressed. E-mail:
picozza@roma2.infn.it
1 GV and 1.2 TV (Fig. 1 and tables S1 and S2), ratio of the two species is independent of the
†On leave from School of Mathematics and Physics, China based on data gathered between 2006 and 2008 solar-modulation parameter and allows Δg for
University of Geosciences, CN-430074 Wuhan, China. with PAMELA, a detector orbiting Earth in a the interstellar spectrum to be measured in the

WorldMags www.sciencemag.org SCIENCE VOL 332 1 APRIL 2011 69


REPORTS
rigidity range of 5 to 30 GV, where solar- Secondly, as seen in Fig. 4, the PAMELA 0:007(stat) T 0:002(syst), which is lower than the
modulation effects dominate. Previous measure- data show clear deviations from a single–power- value fitted between 80 to 230 GV: gR80−230GV,p ¼
ments (20–24) did not have the statistical and law model. The spectrum of protons gradually 2:850 T 0:015(stat) T 0:004(syst). In the case
systematic precision to demonstrate this decrease softens in the rigidity range 30 to 230 GV. In the of helium, gR30 −80GV, He ¼ 2:71 T 0:01(stat) T
in the ratio. rigidity range 30 to 80 GV, gR30−80GV;p ¼ 2:801 T 0:002(syst), which is lower than gR80−230GV,He ¼

Fig. 1. Proton and helium absolute fluxes measured by


PAMELA above 1 GeV per nucleon, compared with a few of the
previous measurements (16–24). All but one of the previous
measurements (24) come from balloon-borne experiments.
Previous data up to few hundred billion electron volts per
nucleon were collected by magnetic spectrometer experiments 104
(20–24), whereas higher-energy data come from calorimetric
measurements. PAMELA data cover the energy range 1 GeV

Flux × E2.7 (m2 s sr GeV/n)-1 × (GeV/n)2.7


to 1.2 TeV (1 to 600 GeV per nucleon for He). The fluxes are
expressed in terms of kinetic energy per nucleon, converted
from the rigidity measured in the tracker and neglecting any
contribution from less abundant deuterium (d/p ≃ 1%) (where
d is deuterium) and 3He (3He/ 4He ≃ 10%). Therefore, pure
proton and 4He samples are assumed. Error bars are statis-
tical and indicate 1 SD; the gray shaded areas represent the
estimated systematic uncertainty. E, kinetic energy per nucleon.
3
10

IMAX (1992)
IMAX (1992) CAPRICE (1994)
CAPRICE (1994)

CAPRICE (1998)
CAPRICE (1998) AMS (1998)
AMS (1998)

ATIC-2 (2007)
ATIC-2 (2007) BESS (2002)
BESS (2002)

CREAM (2004-2006)
CREAM (2004-2006) JACEE (1994)
JACEE (1994)
2
10 RUNJOB (1995-1999)
RUNJOB (1995-1999) PAMELA
PAMELA

PAMELA systematic
PAMELA systematic error
error band
band

2 3 4
1 10 10 10 10
E (GeV/n)

Fig. 2. Proton (top data set) and helium (bottom data set)
fluxes measured by PAMELA in the rigidity range 1 GV to
1.2 TV. The pink shaded areas represent the estimated 104
systematic uncertainty. The lines represent the fit with a
single power law and the GALPROP (36) and Zatsepin (29)
Flux × R2.7 (m2 s sr GV)-1GV2.7

models. Details of the models are presented in tables S1


and S2.

3
10

102
PAMELA
Zatsepin et al. 2006 (fitted to data)
GALPROP φ=450 MV
Zatsepin et al. 2006
Single power law fit
3
1 10 102 10 104
R (GV)

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70 1 APRIL 2011 VOL 332 SCIENCE www.sciencemag.org
REPORTS
2:77 T 0:03(stat) T 0:004 ( syst). We applied At 230 to 240 GV, the proton and helium data proton spectrum occurs at232þ35−30 GV with change
Fisher’s and Student’s t tests to the single–power-law exhibit an abrupt spectral hardening. Applying of spectral index from gR80−232GV;p ¼ 2:85 T
hypothesis in the range 30 to 230 GV for both Fisher’s test and Student’s t test to the proton 0:015(stat) T 0:004(syst) to gR>232GV;p ¼ 2:67 T
protons and helium [see section 5 of the sup- spectrum above 80 GV, the single–power-law 0:03 T 0:05. For the helium data, the single–
porting online material (SOM) for details]. This hypothesis is rejected at 99.7% CL if only sta- power-law hypothesis is rejected at 95% CL
hypothesis is rejected at the 95% confidence level tistical errors are considered. A similar result is with spectral hardening setting in at 243þ27 −31
(CL). Considering the same rigidity interval in obtained if the fluxes are increased in line with GV and a corresponding change of spectral in-
terms of kinetic energy per nucleon, the Fisher’s the systematic uncertainties. If the fluxes are dex of gR80−240GV;He ¼ 2:766 T 0:01 T 0:027 and
and Student’s t tests reject a single–power-law instead decreased, the single–power-law hypoth- gR>243GV;He ¼ 2:477 T 0:06 T 0:03. As a con-
hypothesis at 99.7% CL. esis is rejected at 95% CL. The hardening of the sistency check, we repeated this analysis with
the three highest-energy data points excluded;
no changes in the proton and helium results were
observed. We obtained similar results when we
used alternative statistical methods such as the
cumulative sum test (see section 5.4 in the SOM).
One of the most notable features of the cos-
mic rays before PAMELA observations was their
10 apparently featureless energy spectra. Until now,
single power laws, as predicted by the shock dif-
p/He

fusion acceleration model and diffusive propaga-


tion in the Galaxy [see (25) for a recent review],
could reproduce spectra using similar spectral
indices (a fit to the experimental data yields
PAMELA
g ≃ 2:7) for protons and heavier nuclei up to
Zatsepin et al. 2006 (fitted to data)
GALPROP φ=450 MV
energies of about ≈1015 eV (the so-called “knee”
Zatsepin et al. 2006 region). Such assumptions are routinely incorpo-
Single power law fit
1 3 rated into commonly used propagation models
1 10 102 10 104
R (GV) such as GALPROP (4), which is widely con-
sidered to be the standard model of cosmic-ray
Fig. 3. Ratio of the flux between proton and helium data of PAMELA versus rigidity. The gray shaded area acceleration and propagation. Our results chal-
represents the estimated systematic uncertainty. Lines show the fit using a single power law (describing lenge this scenario (26). As can be seen in Figs. 2
the difference of the two spectral indices) and the GALPROP (36) and Zatsepin models with the original and 3, the GALPROP calculation does not re-
values of the paper (29) fitted to the data. Details of the models are presented in tables S1 and S2. produce PAMELA data across the full-rigidity
region. Moreover, it is difficult, even with recent
Proton Helium
models of nonlinear shock acceleration (27, 28),
to produce significant differences in the proton and
helium spectra as low as a few tens of gigavolts.
The hardening in the spectra observed by
PAMELA around 200 GV could be interpreted as
an indication of different populations of cosmic-
ray sources. As an example of a multisource model,
Fig. 2 shows a comparison with a calculation by
Zatsepin and Sokolskaya (29) (blue curves), which
Flux × R2.7 (m2 s sr GV)-1 GV2.7

Flux × R2.7 (m2 s sr GV)-1 GV2.7

was put forward to explain ATIC-2 data (16) and


considered novae stars and explosions in super-
bubbles as additional cosmic-ray sources. The pa-
rameters of the model were fitted to match ATIC-2
data and, consequently, are in disagreement with
PAMELA data in absolute fluxes and the ratio.
If the parameters of this model are fitted to the
PAMELA data, the agreement can be greatly im-
proved (red curves in Figs. 2 and 3). CREAM
10 4
also reported a direct measurement, albeit with
a low statistical and systematic significance, of
a change of the slope for nuclei (Z ≥ 3) at 200
GeV per nucleon; that is, at a higher rigidity
103 ð≃ 400 GVÞ than our observed break in the he-
lium spectrum.
10 10 2 10 3 10 102 103 An indication that proton and helium have dif-
R (GV) R (GV) ferent spectral indices at high energy (~10 TeV)
Fig. 4. Proton (left) and helium (right) spectra in the range 10 GV to 1.2 TV. The gray shaded area was reported by JACEE (18). More recently,
represents the estimated systematic uncertainty, and the pink shaded area represents the contribution CREAM (17)—also using AMS (alpha magnetic
due to tracker alignment. The green lines represent fits with a single power law in the rigidity range 30 to spectrometer) (24) and BESS (balloon-borne
240 GV. The red curves represent the fit with a rigidity-dependent power law (30 to 240 GV) and with a experiments with a superconducting spectrometer)
single power law above 240 GV. (30) data—indirectly inferred that spectral defor-

WorldMags www.sciencemag.org SCIENCE VOL 332 1 APRIL 2011 71


REPORTS
mation should occur at ~200 GeV per nucleon for tracker, providing absolute charge information and force-field approximation (15), more detailed models, which
both species. This is similar to our results for protons track-deflection (h = T1/R, with the sign depending on use the full Parker equation to describe the propagation of
the sign of the charge derived from the curvature cosmic rays in a two- or three-dimensional heliosphere
but higher (400 GV) than our results for helium. direction) information. A scintillator system, composed of (34, 35), may be needed to fully understand the impact of
Results from ATIC-2 (16) implied that protons three double layers of scintillators (S1, S2, S3 in fig. S2) this effect.
and helium nuclei have different energy spectra, provides the trigger, a time-of-flight measurement, and 27. D. Caprioli, P. Blasi, E. Amato, Astroparticle Phys.;
although the results suffered from unclear sys- an additional estimation of absolute charge. A silicon- preprint available at http://arxiv.org/abs/1007.1925.v2
tungsten tracking calorimeter, a bottom scintillator (S4), (2010).
tematic uncertainties, and there were differences and a neutron detector are used to perform lepton- 28. D. C. Ellison, D. J. Patnaude, P. Slane, P. Blasi, S. Gabici,
with respect to previously reported ATIC-1 (31) hadron discrimination. An anticoincidence system is used Astrophys. J. 661, 879 (2007).
data. off-line to reject spurious event triggers generated by 29. V. I. Zatsepin, N. V. Sokolskaya, Astron. Astrophys. 458,
particles interacting in the apparatus. Respect to balloon- 1 (2006).
borne experiments, PAMELA has the advantage of a 30. T. Sanuki et al., Adv. Space Res. 27, 761 (2001).
References and Notes substantially longer period of uninterrupted observing 31. H. S. Ahn et al., Adv. Space Res. 37, 1950 (2006).
1. P. O. Lagage, C. J. Cesarsky, Astron. Astrophys. 118, 223 time. Furthermore, taking data in space is not affected by 32. P. Picozza et al., Astropart. Phys. 27, 296 (2007).
(1983). environmental systematics such as those due to 33. M. Casolino et al., Adv. Space Res. 42, 455 (2008).
2. V. L. Ginzburg, S. I. Syrovatskii, The Origin of Cosmic Rays correction for secondary particles produced in the 34. J. R. Jokipii, E. H. Levy, W. B. Hubbard, Astrophys. J. 213,
(Macmillan, New York, 1964). residual atmosphere that affects balloon-borne 861 (1977).
3. M. A. Malkov, L. O.’C. Drury, Rep. Prog. Phys. 64, 429 experiments. A more detailed description of PAMELA 35. M. S. Potgieter, J. Atmos. Sol. Terr. Phys. 70, 207 (2008).
(2001). and the analysis methodology can be found in 36. A. E. Vladimirov et al., preprint available at http://arxiv.
4. A. W. Strong, I. V. Moskalenko, Astrophys. J. 509, 212 (32, 33) and in the SOM. org/abs/1008.3642v1 (2010).
(1998). 15. L. J. Gleeson, W. I. Axford, Astrophys. J. 154, 1011 (1968). 37. We thank P. Blasi, F. Donato, P. Lipari, and I. Moskalenko
5. F. C. Jones, A. Lukasiak, V. Ptuskin, W. Webber, 16. J. P. Wefel et al., in Proceedings of the 30th International for helpful discussions concerning the interpretation of our
Astrophys. J. 547, 264 (2001). Cosmic Ray Conference, R. Caballero et al., Eds. results and D. Marinucci for helpful discussions on
6. F. Donato et al., Astrophys. J. 563, 172 (2001). (Universidad Nacional Autónoma de México, Mexico City, statistical methods. We acknowledge support from the
7. M. Amenomori et al., Science 314, 439 (2006). 2008), vol. 2, pp. 31–34. Italian Space Agency, Deutsches Zentrum für Luft- und
8. O. Adriani et al., Nature 458, 607 (2009). 17. H. S. Ahn et al., Astrophys. J. Lett. 714, L89 (2010). Raumfahrt, the Swedish National Space Board, the Swedish
9. O. Adriani et al., Phys. Rev. Lett. 102, 051101 (2009). 18. K. Asakimori et al., Astrophys. J. 502, 278 (1998). Research Council, the Russian Space Agency (Roscosmos),
10. O. Adriani et al., Phys. Rev. Lett. 105, 121101 (2010). 19. M. Hareyama, RUNJOB collaboration, J. Phys. Conf. Ser. and the Russian Foundation for Basic Research.
11. C. Grimani, Class. Quantum Gravity 26, 235009 (2009). 31, 159 (2006).
12. N. Arkani-Hamed, D. P. Finkbeiner, T. R. Slatyer, 20. W. Menn et al., Astrophys. J. 533, 281 (2000).
N. Weiner, Phys. Rev. D 79, 015014 (2009). 21. M. Boezio et al., Astrophys. J. 518, 457 (1999). Supporting Online Material
13. G. Kane, R. Lu, S. Watson, Phys. Lett. B 681, 151 (2009). 22. M. Boezio et al., Astropart. Phys. 19, 583 (2003). www.sciencemag.org/cgi/content/full/science.1199172/DC1
14. PAMELA comprises a number of high-performance 23. S. Haino et al., Phys. Lett. B 594, 35 (2004). SOM Text
detectors, capable of identifying particles through the 24. AMS Collaboration, Phys. Lett. B 490, 27 (2000). Figs. S1 to S6
determination of charge (Z), rigidity (R = pc/|Z|e, where 25. A. W. Strong, I. V. Moskalenko, V. S. Ptuskin, Annu. Rev. Tables S1 to S7
p is the momentum of a particle of charge Ze, c is the Nucl. Part. Sci. 57, 285 (2007). References
speed of light, and e is the electron charge), and velocity 26. The changing spectral characteristics of the proton
(b = v/c, where v is the velocity) over a wide energy spectrum between 30 and 230 GV may be partly due to 18 October 2010; accepted 9 February 2011
range. The device is built around a permanent magnet heliospheric effects. Although solar-modulation effects Published online 3 March 2011;
with a six-plane double-sided silicon microstrip are considered negligible above 30 GV in the spherical 10.1126/science.1199172

Spontaneous Ferroelectric Order in a ically free to adopt any orientation), has not yet
been realized because known molecular archi-
tectures do not have interactions that are strong
Bent-Core Smectic Liquid Crystal of enough to stabilize polar order in the translation-
ally symmetric milieu of a three-dimensional (3D)
Fluid Orthorhombic Layers liquid. The more recent discoveries of spontane-
ous polar ordering (3) and macroscopic chirality
(4) in fluid smectic liquid crystals (LCs) of achiral
R. Amaranatha Reddy,1 Chenhui Zhu,2 Renfan Shao,2 Eva Korblova,1 Tao Gong,1 bent-core molecules, phases of stacked 2D fluid
Yongqiang Shen,2 Edgardo Garcia,1,3 Matthew A. Glaser,2 Joseph E. Maclennan,2 layers, has opened a new path for making ma-
David M. Walba,1 Noel A. Clark2* terials with polar fluid degrees of freedom, exploit-
ing the much stronger intermolecular interaction
Macroscopic polarization density, characteristic of ferroelectric phases, is stabilized by dipolar afforded by their polar steric molecular shape, the
intermolecular interactions. These are weakened as materials become more fluid and of higher exploration of which has generated a rich new
symmetry, limiting ferroelectricity to crystals and to smectic liquid crystal stackings of fluid class of soft materials (5, 6).
layers. We report the SmAPF, the smectic of fluid polar orthorhombic layers that order into a The bent-core fluid lamellar LCs can be grouped
three-dimensional ferroelectric state, the highest-symmetry layered ferroelectric possible and according to whether the constituent 2D layers
the highest-symmetry ferroelectric material found to date. Its bent-core molecular design have an optical dielectric tensor principal axis
employs a single flexible tail that stabilizes layers with untilted molecules and in-plane polar (OPA) along the layer normal (SmA, orthogonal)
ordering, evident in monolayer-thick freely suspended films. Electro-optic response reveals the or not (SmC, monoclinic). The orthogonal achiral
three-dimensional orthorhombic ferroelectric structure, stabilized by silane molecular terminations
that promote parallel alignment of the molecular dipoles in adjacent layers. 1
Department of Chemistry and Biochemistry, Liquid Crystal
Materials Research Center, University of Colorado, Boulder, CO
he first theoretical description of the ordering of its molecular electric dipoles (2). Such 80309–0215, USA. 2Department of Physics, Liquid Crystal

T orientational ordering of liquid crystals


was by Born, who in 1916 formulated an
electric analog of the Curie-Weiss mean-field mod-
a liquid crystal would be the highest symmetry
ferroelectric phase, with only a fluid macroscopic
polarization and its required uniaxial optical an-
Materials Research Center, University of Colorado, Boulder, CO
80309–0390, USA. 3Laboratório de Química Computacional,
Instituto de Química, Universidade de Brasilia, Brasilia DF
70910-900, Brasil.
el of ferromagnetism [see, for example, (1)] to isotropy as broken symmetries. This phase, in *To whom correspondence should be addressed. E-mail:
describe a fluid with spontaneous macroscopic which the polarization would be fluid (energet- noel.clark@colorado.edu

WorldMags
72 1 APRIL 2011 VOL 332 SCIENCE www.sciencemag.org
REPORTS
smectic phases of interest here consist of layers polar fluid smectic layers, typically with a tilted tion in the small-angle region due to the smectic
of one of the symmetries sketched in Fig. 1A: principal axis as in the SmCP of Fig. 2A and layering (Fig. 1) and diffuse scattering with a peak
(i) uniaxial (C∞h), the SmA phase (7), some ex- antiferroelectric 3D interlayer order [compound at a spacing of D ~ 4.6 Å, indicating liquid-like in-
amples of which have high susceptibility for 1 (4)]. Molecules that favor untilted layers and plane order (18). The layer spacing L ~ 61 Å is
field-induced in-plane polar order (8); (ii) uniaxial ferroelectric interlayer order are then obtained re- much larger than the calculated extended (all
polar C∞v, the polar smectic A phase, not yet spectively by (18) (i) reducing the tendency for trans) molecular length Lm ~ 52 Å (18), im-
found in bent-core materials; (iii) nonpolar ortho- tilt by employing molecules with only a single plying a structure in which each layer is non-
rhombic (D2h), the biaxial SmAb phase (9–11); alkyl tail to provide more space for the tails and polar along the layer normal z, with the cores
and (iv) polar orthorhombic (C2v), the SmAP thus lower their in-plane entropic pressure (Fig. strongly overlapping but having half the mole-
phases, with fluid in-plane layer polarization and 2D) (12) and (ii) reducing the tendency for anti- cules in each layer with tails along +z and half
macroscopic antiferroelectric ordering of adja- ferroelectric layer ordering by terminating the tail with tails along –z, in both the SmA and SmAPF
cent layers (SmAPA) (12–17). Here, we report a with a carbosilane group to suppress the inter- phases ( Fig. 1B, inset, and fig. S7) (18).
fluid smectic ferroelectric phase with orthorhom- penetration of tails in adjacent layers (ellipse, Fig. The optical textures of samples of W586 were
bic symmetry, the highest symmetry polar fluid 2C) (19). studied using four distinct preparation methods:
possible in a layered system, leaving only the ful- X-ray, optical, and calorimetric studies of (i) freely suspended films (Fig. 3, F and G, and
ly 3D liquid uniaxial or biaxial polar nematics W586 provide compelling evidence for the target fig. S2) (18); and, with the LC in few-micron-
among higher symmetry polar fluid phases to SmAPF phase. W586 melts upon heating at T = thick gaps between glass plates: (ii) homeotropic
be realized. 110°C and exhibits the following phase sequence cells, made using clean glass plates, yielding ho-
The approach to the design of W586 (Fig. on cooling: isotropic (I) – 155°C – SmA – 136°C – meotropic alignment, i.e., smectic layers parallel
1B) is to start with the bow-shaped structural SmAPF – 80°C – crystal (X). In both the SmA to the plates (Fig. 3, A and E); (iii) random-planar
theme exemplified by the mesogen cores shown and SmAPF phases, synchrotron x-ray diffraction cells, made using nylon films on clean glass or
in Fig. 2, B and E, known to form spontaneously exhibited a resolution-limited, first-order reflec- indium/tin oxide (ITO) coated glass plates, yield-
ing random planar focal-conic textures with the
smectic layers locally normal to the plates (Fig.
3B); and (iv) aligned planar cells, made using
A
rubbed Teflon films on glass or ITO, yielding
planar alignment of oriented smectic layers nor-
mal to both the rubbing direction and the plates
(Fig. 3, C and D).
z The phase identified as SmA gives excellent
extinction between crossed polarizer and ana-
lyzer in the homeotropic geometry (Fig. 3A, left),
evidence for an optical uniaxis normal to the
layers and plates. In contrast, upon cooling to the
B 62.0 phase identified as SmAPF, a distinct Schlieren
z texture of in-layer birefringence appeared (Fig.
3A, right, and 3E), characterized by smooth brush
61.5 p
61Å o patterns indicative of slowly varying optical an-
isotropy and thus revealing in-layer orientational
layer spacing, L (Å)

ordering of the molecular bow planes. Point de-


61.0
SmAPF SmA I fects in the texture exhibited four-brush patterns
52Å when viewed between crossed polarizer and an-
60.5 alyzer, indicating a 2p reorientation of a principal
optic axis about each defect core, and thus polar
W586 ordering (Fig. 3E). Additionally, a quasiperiodic
60.0 pattern of stripes can appear (Fig. 3A, right), each
bi of which marks the termination of a single smectic
Lm ~ 52 Å layer accommodating the spatial variation of the
59.5
gap between the glass plates. The appearance of
X - 80 °C - SmAPF - 136 °C - SmA - 155 °C - I these stripes is analogous to that found due to
59.0 single-layer edge dislocations in homeotropic sam-
ples of rodlike molecules as one passes through
80 100 120 140 the SmA to SmC transition (20). Conoscopy of
temperature, T (°C) the homeotropic W586 samples confirmed uni-
axial order in the SmA phase and locally biaxial
Fig. 1. (A) Symmetries of achiral smectic layers (layer normal, z), where the solid figure represents the
optical dielectric tensor of the layer and the arrow its polarization. We report the SmAPF bent-core phase, ordering with an optic axis normal to the layers
having macroscopic, in-plane ferroelectric ordering of orthorhombic layers with in-plane polarity (C2v). (B) and increasing in-plane birefringence Dn with
Molecular structure, phase diagram, and layer spacing versus T of W586. The layer spacing obtained from decreasing temperature T in the SmAPF phase.
high-resolution synchrotron x-ray diffraction (dq ~ 0.0004Å−1) is about 61Å (18), much larger than the The random-planar samples exhibited focal
calculated extended molecular length, Lm = 52 Å (fig. S7), implying a structure in which each layer is conic textures, which showed a strong increase of
nonpolar along z, with the cores overlapping but with half the molecules in each layer with tails along +z effective birefringence when an electric field of
and half with tails along –z, in both SmA and SmAPF phases (inset). The L(T) of W586 exhibits the typical either sign was applied normal to the plates but
SmA layer expansion with decreasing T as the tails elongate, but in the SmAPF the layers contract. The no accompanying optic axis rotation about the
silane termination of W586 suppresses out-of-layer fluctuations to promote ferroelectric coupling of applied field direction (Fig. 3B), as is observed
adjacent layers. with tilted chiral ferroelectric LCs. This and the

WorldMags www.sciencemag.org SCIENCE VOL 332 1 APRIL 2011 73


REPORTS
observed homeotropic Schlieren texture indicates electrostatic energy accompanying splay distortion tive odd-even polarization effects in such experi-
that one OPA is along the layer normal z and that of P required around the –1 defect (23) (Fig. 3F). ments, as the net P normal to the tilt plane cancels
the other two, p and o, are in the layer plane. In Uncrossing the analyzer shows that P(x,y) is par- for even-N antiferroelectric films (22, 24). In
this frame, the optical dielectric tensor e is dia- allel to p(x,y), the optical fast axis, i.e., P(x,y) = W586 films, no discernible odd-even effects of
gonal, with respective principal optical dielectric Pp(x,y), where P is the polarization magnitude. P were found. The fracturing mentioned above
constants ez = nz2, ep = np2, and eo = no2, where Another consequence of the large energy cost of about –1 defects was found for all film thick-
we choose the p axis to have the higher in-plane splay of P is the thready nature of the fluctuations nesses, indicating large P for all thicknesses and
index (np > no). This orientation of the OPAs, of the film textures, a characteristic of the sup- confirming that the intralayer ordering of P is
together with the sign of birefringence in the pression of splay fluctuations by space charge, ferroelectric in the SmAP phase of W586, i.e.,
planar geometry that indicates that ez is the largest leaving predominately bend fluctuations (green that it is PF.
diagonal term of e, provides direct evidence that circle, Fig. 3G). The optical and x-ray observations showing
this polar smectic phase has the mean molecular Application of an in-plane electric field E ~ the bulk phase to have macroscopic polarity and
long axis normal to the layers, indicating either 10 V/mm provided additional evidence of macro- an OPA along the layer normal indicate that the
the SmAPF, the monolayer phase of on-average scopic polarization, with the films exhibiting a p molecular long axis is on average untilted, i.e.,
untilted molecules, or possibly a phase of tilted rotation of p on field reversal and field stabiliza- oriented along the layer normal, a constraint con-
molecules having a multilayer unit cell, such as tion of 2p walls terminating on the topological sistent with either a bulk SmAPF where the mol-
the bilayer SmCAPF structure shown in Fig. 2F. defects, as is typical of ferroelectric films (21), ecules in every layer are untilted (orthorhombic
Remarkably, a well-aligned planar texture with z and direct confirmation that P is parallel to p. layers, Fig. 2G), or with the SmCAPF where the
parallel to the glass plates and along the rubbing Observations of both the defect structure and layers have alternating molecular tilts (monoclin-
direction was obtained for both the smectic A field response were carried out as a function of ic layers, Fig. 2F) (25). DRLM of freely suspended
phases in rubbed Teflon cells, as shown in Fig. N. Antiferroelectric FSFs always exhibit distinc- films at oblique incidence (22) is an effective way
3C, a rare case in which a smectic phase of ba-
nana molecules has been successfully aligned by
rubbing. two tails one tail
Freely suspended films (FSFs), drawn in air A dtail D
tail tail
with an integer number of smectic layers, N, and
imaged with depolarized reflected light micros- 1,3 da 2 core 5,6 core
dc sublayer
copy (DRLM) (21) with oblique laser illumination, sublayer

have been used to probe coupled in-layer-plane tail tail


SmCP SmAP SmA SmAP SmA
molecular orientation and electric polarization
fields in smectic liquid crystal phases of rodlike temperature, T T
B z 2 C 4 E 5 z
G 6 z
(22) and bent-core molecules (4). Here, we apply F
the DRLM-film technique to W586 to probe the 90° z
p z
p p
ground-state structure of the observed smectic
phase. Films of uniform thickness with N in the p
bi l bi l
range 1 < N < 10, as well as films with layer steps,
were prepared for study by drawing them over a p p
5-mm-diameter hole in a glass cover slip. Film
thickness was determined by laser reflectivity (21).
DRLM observations of W586 films with 90°
oblique incidence (angle of incidence ≈ 7°) reveal SmAPA SmA SmCAPF SmAPA SmAPF
textures of brush patterns and topological defects
similar to those found in SmC films (21) (Fig. 3, 1: R1 = R2 = OC9H19; R3 = X = H
X-72oC-B3-140oC-SmCSPA-158oC-Iso
F and G). Uncrossing the analyzer enables de- 5: R = OC14H29
2: R1 = R2 = OC8H17; R3 = CN; X = F
termination of the local high-index, in-plane ori- X-73oC-SmAPA- TP=145oC -SmA-180oC-Iso X 129.5oC SmAPA 138oC SmA 140.2oC Iso
entation, distinguishing p from o and enabling 3: R1 = OC9H19; R2 = O
O C6H13
; R3 = X = H 6: R = O-(CH2)11
the local azimuthal orientation, y(x,y), of p(x,y) B4-90oC-SmCP (B7)-139oC-Iso
X 80oC SmAPF 136oC SmA 155oC Iso
to be mapped, as indicated in Fig. 3F. The topo- 4: R1 = R2 = O ; R3 = X = H
logical defects (vortices) revealed by the four- B3*-138oC-SmY*-146oC-SmCAPF*-167oC-Iso
brush patterns seen with decrossed polarizer and
analyzer in Fig. 3F show that, as with the ho- Fig. 2. (A) Sketches of the layer structure of the SmA and SmAP phases, found in compound 2 (13), and
meotropic cells, the films only have defects with the SmCP phases, found in compounds 1 (4) and 3 (29). (B) Core structures, showing the opening angle b,
+2p or –2p reorientation of p. The absence of +p which is larger in 2 due to the CN substitution at R3. (C) Supermolecular structure of the SmA and SmAPA
phase observed in 2, showing the average molecular long axis layer, l, parallel to the layer normal z, and
or –p defects is a distinctive signature that locally
the average molecular polar axis p, normal to z. The SmAPA is stabilized by the synclinic ordering and
this in-plane structure is polar, with macroscopic
interpenetration of the molecular tails at the layer interfaces, indicated by the gray lines in the ellipse. The
polar order within each layer. The +2p (+1, blue) SmA phase appears in 2 at higher T. (D) Reducing the number of tails from two to one per molecule
and –2p (–1, red) defects are distinct in that while creates more space for the tails, promoting orthogonal phases. The layer spacing larger than the
the in-plane polarization P(x,y) rotates smoothly molecular length can be understood on the basis of the structure in fig. S7 (18). Steric interaction between
in a bend deformation around the core of the +2p the cores is enhanced at low T, giving the SmAP phases. (E) Bent-core structure of 5 (12) and 6 (W586).
defect, it is broken into four domains, each of (F) In bulk optical experiments, the SmAPF is indistinguishable from the SmCAPF exemplified by compound
nearly uniform orientation, about the –2p defect 4 (25), both having an optic axis along the layer normal. However the SmAPF can be identified in freely
(Fig. 3F). This fracturing of the polarization field, suspended films by the absence of odd/even effects versus layer number, N. (G) Out-of-layer fluctuations
to date observed in polar films in which the mag- (ellipse) enable penetration of tails into the adjacent layers favoring synclinic tail tilt at the layer interfaces
nitude of P is at least several hundred nC/cm2, is and thus macroscopic antiferroelectric (SmAPA) order. Introducing carbosilane into the tail suppresses
a consequence of the space charge and associated out-of-layer fluctuations, favoring anticlinic tail orientation and thus the SmAPF structure.

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74 1 APRIL 2011 VOL 332 SCIENCE www.sciencemag.org
REPORTS
of probing the tilt of the OPA with respect to the ordering of the molecules about the layer normal, where the in-plane quadrupolar order parameter,
layer normal. Our observations, for example, the z, at different temperatures. Application of a Q = (〈cos2fi〉 – 〈sin2fi〉), is the second moment
equal intensity of the four brushes in the DRLM triangle wave voltage v(t) across the cell plates of fluctuations of bi about p. Because e = n2 and
images of N = 1 films (Fig. 3G), show no evidence induces peaks in the optical transmission between Dn is small, the in-plane refractive index an-
for a tilted OPA in W586 films, eliminating the crossed polarizers and a polarization current isotropy is Dn = De/2 n = (ep – eo)/2 n, where
the SmCAPF as a possible structure (18). (inset, Fig. 4B) in the SmAPF phase, indicating the mean in-plane refractive index is given by
qffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffi
In films, the SmA to SmAP phase transition a Goldstone-like response of macroscopic ferro-
n = (n2p þ n2o )=2 ≈ (np þ no )=2. Both P and
was observed at 150°C, slightly elevated relative electric ordering, which we have analyzed in de-
to the bulk, as often found in smectic films. Both tail. The field couples to P, tending to minimize Q will depend on temperature T.
the response to applied electric field and the in- the electrostatic potential energy density –P•E = We consider planar alignment so that z is
plane birefringence decrease substantially with –PEcosy, by varying the azimuthal orientation parallel to the glass, giving an index nz = ez1/2 for
increasing temperature in the SmAPF phase but y of P, where we take y = 0 when P is parallel light polarized along z and incident normally on
do not disappear completely even in the SmA to E (Fig. 4A) . In molecular terms, P = Pp = the cell. The effective in-plane index, neff (y), for
phase. Fine-texture birefringence patterns persist Pm〈p • bi〉p = pPm〈cosfi〉, where fi gives the light polarized normal to z is given by 1/neff (y)2 =
into the SmA phase and only gradually disappear azimuthal orientation of the bow plane bi of mol- sin2y/np2 + cos2y/no2, and the planar cell trans-
with increasing temperature, suggestive of rem- ecule i relative to the mean orientation p (Fig. 1B), mission, for crossed polarizer and analyzer at 45°
nant biaxial ordering on the surfaces of internally Pm is the molecular polarization density, and to z, by T(y) = sin2[pdn(y)d/l], determined by
uniaxial films. 〈cosfi〉 is the polarization orientation order param- the resulting effective birefringence dn(y) ≡ nz –
The electrical and optical responses of W586 eter, the first moment of fluctuations of orienta- neff (y), cell thickness d, and wavelength l. The
to an applied electric field, E, and surface tions of individual molecular bow planes bi about peaks in the T(y) data were used to extract the
interactions in planar-aligned ITO-on-glass cells the mean orientation p(y). Similarly, the in-plane dependence of y on applied voltage, y(v), under
were used to probe the azimuthal orientation and dielectric anisotropy is De = ep – eo = DemaxQ, the assumption that np – no is independent of y

A SmA homeotropic SmAPF homeotropic cell freely suspended


E SmAPF
+1

P P +1
A A
z z
B planar SmAPF SmAPF
-1
-1 z
F
p
E = +10 V/ m 0 V/ m -10 V/ m

C aligned planar D planar


-1

z G

SmA SmAPF E = 0 SmAPF

Fig. 3. Transmitted light optical textures in white light of W586 between yellow). (E) Clean glass preparation with the LC sample ~1 mm thick and layers
treated glass plates viewed between crossed polarizer and analyzer, oriented parallel to the plates. Defects exhibit four-brush patterns between crossed
as indicated for all images. (A) Clean glass preparation with layers parallel to analyzer and polarizer, indicating a 2p reorientation of an optic axis about
the plates and LC layer ~1mm thick. Extinction indicates the uniaxial symmetry each defect core, and thus polar ordering in the SmAPF phase. (F) Freely
of the SmA phase, and the optical biaxiality of the SmAPF phase generates a suspended films with layers parallel to the image plane. DRLM images in the
Schlieren texture, periodically influenced by single smectic layer edge dis- SmAPF phase with oblique incidence and slightly uncrossed polarizers reveal a
locations. (B) Nylon films on glass give random-planar focal conics with the texture of brush patterns, confirming the biaxiality of the SmAPF phase. The
layers normal to the plates in a 5.0-mm-thick cell. At zero field, the bow-plane absence of +p or –p defects indicates that the in-plane order is locally polar.
director is nearly parallel to the glass plates, exhibiting smaller apparent bi- The –2p defect is broken into four domains of nearly uniform in-plane
refringence nz – np, whereas at E = T 10 V/mm the bow-plane director is nearly polarization about the defect core, a consequence of the space charge and
perpendicular to the glass plates, exhibiting larger apparent birefringence nz – no. associated electrostatic energy accompanying splay distortion of P. The +2p
Brushes aligned along analyzer/polarizer with or without field indicates the defect avoids splay of P by adopting the indicated bend-only orientation. This
SmA-like structures in both cases. (C) Teflon-rubbed films on glass give uni- suppression of splay of P also produces the thready texture of largely bend
form planar alignment with the layer normal z along the rubbing direction fluctuations in (F) and (G) (green circle). (G) Single-layer (N = 1) freely
(arrow) in both SmA and SmAPF phases in a 3.6-mm-thick cell. (D) Tilting the suspended film exhibiting equal intensity bright brushes emanating from a +2p
cell about z enables visualization of domains of opposite sign of y, shown defect viewed with crossed polarizer and analyzer, indicating an OPA normal
schematically in cross sections of the cell in the insets (glass plates shown in to the film.

WorldMags www.sciencemag.org SCIENCE VOL 332 1 APRIL 2011 75


REPORTS
Fig. 4. (A) Birefringence (18). Keeping only the first- and third-harmonic
of planar-aligned cells
nz - no A amplitudes in U(fij) is enough to describe P(T )
v = 8V
measured using a Berek
0.11 E _ and Q(T ) versus T very well, the resulting U(fij)
compensator with nor-

birefringence (Δn-nz-neff)
nz - n exhibiting a sharp minimum at fij = 0 and a max-
mally incident white light. imum at fij = p. These features respectively give the
On cooling the SmAPF
0.10
n nz - np correct saturation behavior of P(T ) and yield the
phase, the birefringence observed Q(T) º P(T)2. (ii) SmA/SmAB/SmAPF
with field on, nz – no, v = 0V phase diagram. Using a mean-field Hamiltonian,
increases and the bire- light Radzihovsky, Weichman, and Park have calcu-
0.09
fringence without field, 0.8 _ lated the phase behavior of Bose-Einstein con-
nz – np, decreases, indi- 0.6
cos
(nz - n)A densates (BECs) across a Feshbach resonance,
cating a reduced fluctu-
ation in y, where y is
0.08 0.4 p showing that they can exhibit distinct normal
z fluid (NF), atomic superfluid (ASF), and molec-
the azimuthal orienta- 0.2
tion of the p-l plane. v(t) (Volts) o ular superfluid (MSF) phases (28). We argue that
0.07 0 this Hamiltonian is the same as that for our smec-
The insets show schemat- 0 1 2 3 4 5 6
ically the polarization tic system and use the NF/ASF/MSF phase di-
orientation in the cell SmAPF SmA agram to map that of the SmA/SmAb/SmAPF
(glass plates shown in phases, respectively (18). (iii) Landau-deGennes
polarization (nC/cm2)

yellow). The plot shows 400 P (LdG) Model. The BEC Hamiltonian reduces to
cosy versus the cell volt- n a LdG expansion in the scalar order parameters P
age v(t) in the SmAPF and Q (18). Application of this expansion to the
phase. The linear depen- 300 SmAPF phase describes the SmAPF well, giving
B
dence of v(t) on cosy the dotted black curve in Fig. 4B for P(T) as well
suggests a typical “V- as the required Q(T) º P(T)2.
200
shaped” reorientation of The MMF and LdG models agree well except
P (26, 27), a consequence in the transition regime, where the LdG gives a
of the total screening of second-order transition and the MMF a first-order
100
the applied voltage in transition. As mentioned above, we cannot dis-
the LC by the component tinguish these cases experimentally because, in
of P normal to the cell the cells studied, the measurement of P requires
plates. (B) The current as- 80 100 120 140
an applied field large enough to induce signifi-
sociated with field-induced temperature (°C) cant polarization near the transition (fig. S6).
polarization reorienta-
tion in the SmAPF phase (inset) exhibits a peak due to the analog reorientation of P, which was integrated
References and Notes
to give the macroscopic polarization P. The MMF model gives the red and magenta curves for Dn in (A) and 1. N. W. Ashcroft, N. D. Mermin, Solid State Physics
the red curve for P in (B) (18), and the dashed black curve is the LdG prediction (18).
pffiffiffiffiffiComparison
ffi pffiffiffi of the (Holt, Rinehart Winston, New York, 1978).
dependence of Dn( T ) (blue squares) and P(T ) (white squares) shows that P º Dn º Q is rather 2. M. Born, Sitzungsber. Konigl. Preuss. Akad. Wiss. 1916
well satisfied, a relationship shown by the models to indicate that P drives Q (18). (Jan.–July), 614 (1916).
3. T. Niori, T. Sekine, J. Watanabe, T. Furukawa, H. Takezoe,
J. Mater. Chem. 6, 1231 (1996).
4. D. R. Link et al., Science 278, 1924 (1997).
and that y is uniform through the cell thickness. Differential scanning calorimetry of the SmA to 5. H. Takezoe, Y. Takanishi, Jpn. J. Appl. Phys. 45, (2A),
This analysis shows that v(t) º cosy(t) (inset SmAPF transition shows a weak anomaly, indi- 597 (2006).
of Fig. 4A), just the result first obtained in the cating a second-order or weakly first-order tran- 6. R. A. Reddy, C. Tschierske, J. Mater. Chem. 16, 907 (2006).
“V-shaped” reorientation of P in high-polarization sition (fig. S9). 7. I. Wirth et al., J. Mater. Chem. 11, 1642 (2001).
8. Y. Shimbo et al., Phys. Rev. Lett. 97, 113901 (2006).
chiral SmC materials, shown to be a conse- The mean in-plane refractive index is shown 9. H. R. Brand, P. E. Cladis, H. Pleiner, Int. J. Eng. Sci. 38,
quence of the total screening of the applied voltage as nz – n (green line) in Fig. 4A. These data indi- 1099 (2000).
in the LC by the component of P normal to the cate a difference in nz – n and in np – no = Dn(T) º 10. T. Hegmann, J. Kain, S. Diele, G. Pelzl, C. Tschierske,
cell plates (26) and recently demonstrated in a Q(T) across the cross-hatched SmA–SmAPF tran- Angew. Chem. Int. Ed. 40, 887 (2001).
11. R. Pratibha, N. V. Madhusudana, B. K. Sadashiva, Science
SmCAPF bent-core phase (27). In this model, sition region, interestingly with no corresponding 288, 2184 (2000).
evt = 2dPcosy[v(t)], where e and d are respec- detectable discontinuity in L(T) there, even with 12. B. K. Sadashiva, R. A. Reddy, R. Pratibha, N. V. Madhusudana,
tively the dielectric constant and the thickness of high x-ray diffraction resolution (dd = 0.02 Å, Fig. J. Mater. Chem. 12, 943 (2002).
the insulating alignment layers on the electrode 1B), although L(T ) does go through a maximum 13. A. Eremin et al., Phys. Rev. E Stat. Nonlin. Soft Matter
Phys. 64, 051707 (2001).
plates. The ~12 V width of the 0° < y < 180° in the vicinity. Comparison of the T-dependence 14. R. A. Reddy, B. K. Sadashiva, J. Mater. Chem. 14, 310 (2004).
peaks is consistent with estimates of e and d and of Dn(T)pffiffiffiffiffi
and
ffi P(T ) shows thatpthe ffiffiffiffi relationship 15. S. T. Wang et al., Phys. Rev. E Stat. Nonlin. Soft Matter
the measured P (26). These observations pro- PðTÞº Dn and thus PðT Þº Q is rather well Phys. 70, 061705 (2004).
vide a self-consistent confirmation of the “block satisfied (Fig. 4B, blue and white squares, and 16. B. Glettner, S. Hein, R. A. Reddy, U. Baumeister,
C. Tschierske, Chem. Commun. (Camb.) 25, 2596 (2007).
polarization” mode of field-induced reorientation fig. S3). 17. C. Keith, M. Prehm, Y. P. Panarin, J. K. Vij, C. Tschierske,
of y (reorientation with y spatially uniform) and Several theoretical approaches were pursued Chem. Commun. (Camb.) 46, 3702 (2010).
enables the measurement of nz – no (at y = 0°) to understand these data and to guide exploration 18. Materials and methods are available as supporting
material on Science Online.
and nz – np (at y = 90°), shown in Fig. 4A. The of other novel phase behavior (18), for example,
19. W. K. Robinson, C. Carboni, P. Kloess, S. P. Perkins,
magnitude P(T) is determined by integrating the the SmAb and polarization splay modulated phases: H. J. Coles, Liq. Cryst. 25, 301 (1998).
polarization current peak in Fig. 4B. Behavior (i) Variational molecular mean-field (MMF) XY 20. R. B. Meyer, B. Stebler, S. T. Lagerwall, Phys. Rev. Lett.
in the vicinity of the SmA to SmAPF transition Model. The P(T ) and Q(T ) data were fit to a 41, 1393 (1978).
21. R. Pindak, C. Y. Young, R. B. Meyer, N. A. Clark,
(red crosshatched area, Fig. 4) is difficult to assess generalized 3D XY lattice model with a nearest- Phys. Rev. Lett. 45, 1193 (1980).
because the field required to measure P itself in- neighbor interaction potential U(fij) expressed as 22. D. R. Link, J. E. Maclennan, N. A. Clark, Phys. Rev. Lett.
duces a substantial polarization (fig. S5) (18). an expansion in circular harmonics in fij = fj – fi 77, 2237 (1996).

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REPORTS
23. D. R. Link, N. Chattham, J. E. Maclennan, N. A. Clark, 28. L. Radzihovsky, P. B. Weichman, J. I. Park, Ann. Phys. Supporting Online Material
Phys. Rev. E Stat. Nonlin. Soft Matter Phys. 71, 021704 323, 2376 (2008). www.sciencemag.org/cgi/content/full/332/6025/72/DC1
(2005). 29. D. M. Walba et al., Science 288, 2181 (2000). Materials and Methods
24. P. M. Johnson, S. Pankratz, P. Mach, H. T. Nguyen, 30. This work was supported by NSF Materials Research SOM Text
C. C. Huang, Phys. Rev. Lett. 83, 4073 (1999). Science and Engineering Center grant DMR 0820579, Figs. S1 to S9
25. M. Nakata et al., Liq. Cryst. 28, 1301 (2001). NSF grant DMR 0606528, NSF grant DMR 0603223, and
References
26. N. A. Clark, D. Coleman, J. E. Maclennan, Liq. Cryst. 27, NASA grant NAG-NNC04GA50G. Use of the National
985 (2000). Synchrotron Light Source was supported by the U.S.
27. M. J. O’Callaghan, M. D. Wand, C. M. Walker, M. Nakata, Department of Energy, Divisions of Materials and 2 September 2010; accepted 15 February 2011
Appl. Phys. Lett. 85, 6344 (2004). Chemical Sciences. 10.1126/science.1197248

Heavily Doped Semiconductor for color center impurities (12) and magnetic
impurities, notably Mn atoms (13, 14), thereby
providing insight into the challenging chemistry
Nanocrystal Quantum Dots (15). The introduction of dopant precursors at
specific stages of nanoparticle growth has been
David Mocatta,1,2 Guy Cohen,3 Jonathan Schattner,2,4 Oded Millo,2,4* Eran Rabani,3* Uri Banin1,2* effective in controlling the impurity location (16).
More recently, some progress has been made to-
Doping of semiconductors by impurity atoms enabled their widespread technological application in ward producing n-type CdSe quantum dots (QDs)
microelectronics and optoelectronics. However, doping has proven elusive for strongly confined through the use of tin and indium impurities
colloidal semiconductor nanocrystals because of the synthetic challenge of how to introduce single (17, 18), and Cu impurities have been used to
impurities, as well as a lack of fundamental understanding of this heavily doped limit under strong produce p-type InP NCs (19).
quantum confinement. We developed a method to dope semiconductor nanocrystals with metal Here, we describe a simple room-temperature
impurities, enabling control of the band gap and Fermi energy. A combination of optical method for doping semiconductor NCs with metal
measurements, scanning tunneling spectroscopy, and theory revealed the emergence of a confined impurities. By changing the dopant type and con-
impurity band and band-tailing. Our method yields n- and p-doped semiconductor nanocrystals, centration, we achieved exquisite control of the
which have potential applications in solar cells, thin-film transistors, and optoelectronic devices. electronic properties, including the band gap and
Fermi energy. We conducted experimental and
oping of bulk semiconductors, the pro- injection, has been shown to yield n-type doping theoretical studies of the role of strong quantum

D cess of intentional insertion of impurity


atoms into a crystal, was introduced in
the 1940s and is the basis for the widespread ap-
in semiconductor NC superlattices (4, 9–11).
Substitutional doping has been studied mainly
confinement leading to localization of the im-
purity wave functions as well as disorder effects

plication of semiconductors in electronic and


electro-optic components (1). Controlling the size A B
and dimensionality of semiconductor structures is
Single Scattered
an additional way to tune their properties via quan- Impurity Z-model Impurities
tum confinement effects. In this respect, colloidal
semiconductor nanocrystals (NCs) have emerged
as a family of materials with size-dependent op-
tical and electronic properties. Combined with
their capability for wet-chemical processing, this
has led to NC-based light-emitting diodes (2),
solar cells, (3) and transistor devices (4) prepared
via facile and scalable bottom-up approaches.
Impurity doping in such colloidal NCs still re-
mains a challenge (5). From the synthesis side,
the introduction of a few impurity atoms into a
NC that contains only a few hundred atoms may
lead to their expulsion to the surface (6–8) or com-
promise the crystal structure. This will inherently
create a heavily doped NC under strong quantum
confinement. The electronic and optical properties
in such circumstances are still unresolved.
Several strategies for NC doping have been
used. Remote doping, through the use of bind-
ing ligands on the nanoparticle surface (which
can donate carriers) or electrochemical carrier
Fig. 1. Diagrams describing the effects of heavy doping in bulk and nanocrystal semiconductors. (A)
Scheme of the different influences of doping a bulk semiconductor for n-type (left) and p-type (right)
1
Institute of Chemistry, Hebrew University, Jerusalem 91904, dopants. ABS, absorption onset; PL, photoluminescence onset; TS, tail states; Ef, Fermi energy; E′g,
Israel. 2Center for Nanoscience and Nanotechnology, Hebrew modified band gap; Eg , unperturbed band gap. The purple shading shows state filling up to the Fermi
University, Jerusalem 91904, Israel. 3School of Chemistry,
energy. (B) Sketch for n-doped nanocrystal QD with confined energy levels. Red and green lines
Sackler Faculty of Exact Sciences, Tel Aviv University, Tel Aviv
69978, Israel. 4Racah Institute of Physics, Hebrew University, correspond to the QD and impurity levels, respectively. Left panel: The level diagram for a single
Jerusalem 91904, Israel. impurity effective mass model, where E′g is the quasi-particle gap in the doped QD, 1Se and 1Pe are the
*To whom correspondence should be addressed. E-mail: QD electron levels, and Ed1S and Ed1P are the impurity levels shifted below the corresponding QD levels
uri.banin@huji.ac.il (U.B.); rabani@tau.ac.il (E.R.); milode@ by a shift D. Right panel: Impurity levels develop into impurity bands as the number of impurities
vms.huji.ac.il (O.M.) increases. Upper panel: Sketch of the different impurity models.

WorldMags www.sciencemag.org SCIENCE VOL 332 1 APRIL 2011 77


REPORTS
leading to band-tailing in small NCs. The meth- uene solution with appropriate surfactant and electron spectroscopy (XPS) measurements of
od yields n- and p-doped semiconductor NCs gradually added to a solution of preformed InAs these samples were also performed, indicating the
that greatly enhance the usefulness of such ma- NCs in toluene at room temperature (26). The presence of Ag, Au, and Cu in the respective
terials in solar cells, thin-film transistors, and use of preformed NCs allows changes to the samples (figs. S11 and S12). This suggests suc-
optoelectronic devices. properties of the NCs to be assigned wholly to cessful addition of these atoms to the InAs
Adding even a single impurity atom to a the introduction of the impurity atoms. In gen- NCs, consistent with our previous report of Au
semiconductor NC with a diameter of 4 nm, eral, previous doping methods are based on im- growth on InAs NCs, which exhibited the room-
which contains about 1000 atoms, leads to a purity introduction during NC synthesis, and temperature solid-state diffusion of Au into the
nominal doping level of 7 × 1019 cm–3. In a bulk hence assigning changes to the NC properties NC (25). Indeed, extrapolating the diffusion pa-
semiconductor this is already well within the are complicated by the inability to differentiate rameter values to room temperature gives a dif-
heavily doped limit, where metallic (“degenerate”) between the influence of the impurity on the NC fusion length scale of ~104 nm per 24 hours, far
behavior is expected (20). Heavy doping in bulk and the influence of the impurity precursor on greater than the NC diameter; large values are
semiconductors leads to several effects summa- the synthesis. This well-controlled approach al- also extrapolated for Ag and Cu (table S1).
rized in Fig. 1A. The impurities interact with each lows us to follow the intricate changes in the Figure 2B shows the absorption and emis-
other and an impurity subband emerges near the NC properties upon introduction of dopants. sion (inset) spectra of undoped and doped InAs
edge of the respective band (conduction or va- Figure 2A shows a transmission electron mi- NCs. The addition of Ag atoms results in a red
lence for n- or p-type, respectively). Indeed, this croscope (TEM) image of Ag-doped NCs. At shift of both the first exciton absorption and the
is the criterion that defines the heavily doped the impurity levels reported below, it was not emission peaks. The addition of Cu results in a
regime. Often, tail states (Urbach tails) also de- possible to identify the presence of metal regions, blue shift of the first exciton absorption peak,
velop as a result of distortions in the crystal struc- indicating that the impurity atoms are dispersed whereas the emission is not shifted. Addition of
ture (21). In effect, the band gap Eg is narrowed. (fig. S8). This was not the case for very high Au at similar concentrations does not consider-
This may be probed by optical means, where for metal atom concentrations (>3000 atoms per NC ably alter the observed optical gap either in ab-
heavily doped n-type semiconductors (Fig. 1A, in the reaction solution), where TEM analysis sorption or in emission. The addition of any of
left frame) the absorption is blue-shifted as a re- clearly showed phase separation between InAs these impurity atoms results in the gradual quench-
sult of conduction band-filling by the donated and impurity metal regions (25). Further support ing of the emission from the NCs, yet the three
electrons (Moss-Burstein effect) (20), and the emis- for the dispersion of impurities is provided by impurities lead to qualitatively different effects
sion emanating from the bottom of the conduction x-ray diffraction (fig. S10), where no fingerprints on the optical spectra and hence on the electronic
band is red-shifted. For heavy p-type doping, both of metal domains were detected while the InAs properties of the doped NCs. The effect of vary-
absorption and emission are typically seen to be crystal structure was generally maintained. Some ing amounts of impurities on the first absorption
red-shifted. This is due to the high density of broadening of the peaks is seen, ascribed to a peak and on the emission is shown in Fig. 2, C to
states (DOS) near the valence band edge, leading small degree of structural disorder. X-ray photo- E, for InAs NCs with different diameters (see figs.
to a small Moss-Burstein effect that is often over-
come by the red shift due to band-tailing (20).
A markedly different situation arises for im- B
purity doping of NCs because of the discrete na-

OD
ture of the quantum-confined states (shown for
n-type doping in Fig. 1B). In this case the addi-
OD

tion of a single dopant (left frame) introduces 900 1000 1100 1200
impurity levels that significantly alter the DOS— Wavelength

a situation that is not expected for prior remote


surface doping strategies. This has been described
by a hydrogenic model under spherical confine-
ment, leading to S- and P-like impurity states 600 800 1000 1200 1400
denoted by Ed1S and Ed2P that are several tens of Wavelength (nm)
meVs below the corresponding dot levels, ef- 50
fectively doubling the DOS near those ener- C R=1.3nm D R=1.8nm