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PUBLISHED BY THE AMERICAN CHEMICAL SOCIETY
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OCEAN ACIDIFICATION
Shellfish die-off threatens
Pacific Northwest P. 36
CURBING BEE LOSSES
Groups aim to reduce
pesticide exposure P. 30
LOOKING BEYOND LITHIUM
The search for better bipolar disorder drugs P. 15
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CENEAR 91 (12) 156 I SSN 0009-2347
VOLUME 91, NUMBER 12
MARCH 25, 2013
47 ACS COMMENT 56 NEWSCRIPTS
51 AWARDS
52 CLASSIFIEDS
4 LETTERS
5 EDITORS PAGE
COVER: Getty Images/Shutterstock/C&EN
50 COUNCIL PREVIEW
Spring ACS national meeting in New Orleans will
include candidate selections and petitions.
48 CHEMISTRY INSPIRES ART
The central science acts as high schoolers muse
in ACS Southern Nevada Section poster contest.
41 CUTTING LECTURES IN THE CLASSROOM
Use of online course materials allows for more
personalized instruction in class.
44 THE FUTURE
Former vice president Al Gore provides his vision
of six most important drivers of global change.
We breathe it.
We live it. We are
chemistry.
ASHLEY ARMENTA ,
GRADE 9 , SOUTHEAST
CAREER TECHNICAL
ACADEMY IN LAS
VEGAS PAGE 48
38 ANGEWANDTE CHEMIE TURNS 125
Chemists from around the world gather to
celebrate the journals milestone.
36 OCEAN ACIDIFICATION CONSEQUENCES
Acidic Pacific Northwest waters threaten local
tribe and shellfish industry.
34 CONCENTRATES
32 FALLOUT OF TRAVEL RESTRICTIONS
Critics argue that limits on federal scientists
travel may cost more, stifle scientific progress.
30 HELP FOR HONEYBEES
Consortium develops measures to bring down
pesticide-contaminated dust.
29 CONCENTRATES
26 CABBS FORAY IN CHINA
German firm will make monochloroacetic acid in
a small northern city.
24 BETTING ON BIOBETTERS
Some pharma firms see improved biologics as
having higher returns and fewer pitfalls than near
copies.
22 CONCENTRATES
13 OBAMA DRIVES VEHICLES OFF OIL
President proposes $2 billion for electric vehicle
R&D, biofuels, and more.
13 INSECURITY ABOUT FACILITIES
Federal officials claim progress on chemical plant
security, but skeptics abound.
12 BIONIC VISION IN SIGHT
Polymeric device restores function in rat retinas.
12 CAUTIOUS AT PITTCON
Executives at the instrumentation show are
circumspect about the outlook for 2013.
11 FEDERAL BUDGET PROGRESS
Congress moves to avoid shutdown, aids some
science agencies.
11 SIDESTEPPING A DEATH RECEPTOR
Dangerous serotonin receptor is flagged for drug
designers in new crystal structures.
10 THREE-WAY SHAPE-SHIFTERS
Moving gel sheets could control drug delivery or
robotic devices.
10 DOWS GULF COAST EXPANSION
Firm plans facilities to make high-value
derivativesall thanks to U.S. shale gas.
9 ASTRAZENECA CUTS AND REVAMPS
Pharma giant will lay off thousands and refocus
R&D on three areas.
IMPROVING
BIPOLAR
DISORDER
TREATMENT
Widely used drug lithium
can be toxic, but its
mysterious mechanism
may hold the key to
alternatives. PAGE 15
QUOTE
OF THE WEEK
COVER STORY
NEWS OF THE WEEK
BUSINESS
GOVERNMENT
& POLICY
SCIENCE & TECHNOLOGY
THE DEPARTMENTS
BOOKS
EDUCATION
ACS NEWS
38
56
4
WWW.CEN-ONLI NE.ORG MARCH 25, 2013
THIS WEEK
ONLINE
LETTERS
Latest On The Watch Glass
To celebrate its 90th anniversary, C&EN
earlier this year
launched The
Watch Glass,
a Tumblr site
that explores
the magazines
history through
pictures and
quotes. This
week, check
out a 1948 cov-
er story on bio-
chemist Gerty
Corithe first
American
woman to win
a Nobel Prize in scienceand a 1969
photograph of a research chemist play-
ing chess with laboratory glassware.
http://cen.watchglass.org
New Design Lowers Power
Demands Of Digital Memory
Personal electronics often store data in
devices called flash memory. For years,
engineers have worked on an alterna-
tive called phase-change memory that
can read and write data a thousand
times faster than flash memory. But
progress has been slow because this
alternative consumes relatively large
amounts of power. A new device design
involving silica nanostructures uses just
5% of the power of traditional phase-
change memory.
http://cenm.ag/mat43
Traditional Harvest
On Cape Flattery in Washington state,
members of the Makah tribe search
through tide pools and brave crashing
waves to harvest barnacles and other
shellfish. The waters along the cape are
becoming more acidic (see page 36),
which could weaken the shellfishes
hold on coastal rocks. A video provides
a look inside a harvest and explains how
changing water conditions could disrupt
the traditional way of life for the Makah.
http://cenm.ag/mkh
ACS Committee Reports
At the ACS Board meeting last Decem-
ber, governance committees discussed
many topics including a proposed So-
ciety of Teachers of Chemistry, a three-
year alliance with the South African
Chemical Institute, and an increase in
cash prizes for some ACS awards. This
week, C&EN compiles official reports
from the committees.
http://cenm.ag/qc
C
&
E
N
THE EDITORIAL ABOUT awards sea-
son prompts my every-five-years-or-so
harangue about the awards given by the
AND THE WINNER IS NOT
AN EXPLOSIVE TRAGEDY
AS A CHEMIST with more than 50 years
involvement with display fireworks, I find
it appalling that in the Donaldson Enter-
prises Inc. incident the safest and most
obvious means of disposal was apparently
never considered ( C&EN, Jan. 28, page 26 ).
Simply firing the materials normally and
allowing them to function as designed in
a safe place would have been a far better
course of action.
Display fireworks are fundamentally
different from munitions and other classes
of explosives in too many ways to list here.
But following are a few of the more salient
differences applicable to disposal: They
are often complex in construction, not
designed with disassembly in mind, and
widely varied in the number of different
pyrotechnic compositions that might be
present in a single device. They are not reli-
ably destroyed by water or other liquids,
are perilous to cut into, and are dangerous
to mass-incinerate whether wet or dry.
Disposal involving such methods requires
great caution and a full knowledge of the
product and should be reserved only for
situations where conventional firing is
impossible.
It appears that the materials in this case
were not damaged or defective, but were
merely mislabeled. Had they been properly
marked and classified for professional use,
they would have been perfectly suitable
for that purpose. Therefore, there was no
practical necessity for disposal by unusual
means.
This raises the question of whether the
root cause of this tragedy was, in fact, bu-
reaucratic: Might arbitrary yet rigid proto-
cols have precluded a far safer and simpler
disposal? It would not be the first time that
safety has been sacrificed upon its own al-
tar by misguided policy.
John Bergman
Milton , Wis.
ANECDOTALLY AUTOGRAPHED
I THOROUGHLY ENJOYED Bethany Hal-
fords The Autograph Collector, which
describes the 40-plus-year collection of
chemists signatures diligently gathered
by Tetsuo Nozoe ( C&EN, Jan. 21, page 28 ).
A number of us enjoy this hobby, theme
included. Roald Hoffmanns comment in
the article brought to mind a 2001 incident
in San Diego that led to a unique pair of
autographs.
The occasion was the 221st American
Chemical Society national meeting,
which coincided with the world premiere
of Oxygen, a stage play written by
Hoffmann and Carl Djerassi. During the
meeting exposition, the plays publisher
arranged a meet-the-authors book sign-
ing event. I was first in line when Djerassi
arrived. He was in a particularly playful
mood and decided to sign my volume
as Carl Hoffmann. When Hoffmann
arrived a few minutes later, he signed
the book as Roald Djerassia truly
memorable keepsake of an unforgettable
encounter.
Philip E. Rakita
Hendersonville , N.C.
AAAS CHEMISTRY
SECTION REQUEST
THE RECENT American Association for
the Advancement of Science annual meet-
ing in Boston featured many contributions
of chemistry to science and society. Ses-
sions supported by the Chemistry Section
of AAAS ranged from advances in actinide
science to beneficial new materials in-
spired by biology to a new vision of chemis-
try graduate education.
We ask those of you who are AAAS
members to check that you have affili-
ated with AAAS Section C (Chemistry).
The process is straightforward. Log
on to http://membercentral.aaas.org,
click on Membership and then Man-
age Membership. Affiliation with the
Chemistry Section does not cost anything
extra. Boosting the membership of Sec-
tion C will provide additional funds for
chemistry programming at future AAAS
annual meetings. Please help us increase
membership within the AAAS Chemistry
Section.
Alison Butler , past-chair
Santa Barbara , Calif.
Al Sattelberger , chair
Argonne , Ill.
AAAS Section C (Chemistry)
Continued on page 6
5
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Published by the AMERICAN CHEMICAL SOCIETY
Madeleine Jacobs, Executive Director & CEO
Brian Crawford, President, Publications Division
EDITORIAL BOARD: Stephanie L. Brock (Chair);
ACS Board of Directors Chair: William F. Carroll Jr.;
ACS President: Marinda Li Wu; Leah McEwen, John
N. Russell Jr., Nicole S. Sampson, Peter J. Stang
Copyright 2013, American Chemical Society
Canadian GST Reg. No. R127571347
Volume 91, Number 12
Editor-in-chief
Views expressed on this page are those of the author and not necessarily those of ACS.
To celebrate C&ENs 90th anniversary, one
Editors Page each month will examine materi-
als from C&EN Archives. Featured articles are
freely downloadable for one month.
LIKE C&EN, the Priestley Medal turns 90
this year. C&EN celebrates the medalists
with a profile and publishes their award ad-
dress in full. C&ENs April 8 issue will fea-
ture 2013 Priestley Medalist Peter J. Stang,
Distinguished Professor of Chemistry at the
University of Utah and editor-in-chief of
the Journal of the American Chemical Society.
Stang will deliver his address on April 9 at
the ACS national meeting in New Orleans.
C&ENs tradition of publishing the
Priestley Medal address appears to have
started with the 1945 Priestley Medalist,
Sir Ian Morris Heilbron . Awardees use
the address in different ways. Many give a
retrospective of their work. Others grapple
with societal questions through the lens of
chemistry. I found it strangely reassuring
that many challenges facing the chemistry
enterprise now are not unique, as the fol-
lowing excerpts show. If people have seen
these problems before and have persevered
and grown, so can we.
The first aim of our Society since its
very foundation has been the publication
of chemical research. Let us not be diverted
from this important and inspiring under-
taking. Instead, let us redouble our efforts
so that, in spite of the flood of manu-
scripts, we can publish promptly, clearly,
and economically all the novel, valid, and
significant research in chemistry that we
receive! Arthur B. Lamb , 1949
More young people are not studying
science because their minds, and those
of their parents, have been poisoned by
the insidious cloud of anti-intellectualism
which hangs over this country like a great
shroud. Charles A. Thomas , 1955
Now more than ever, the public image
of science has become the responsibility
of scientists. The purposeful nature of our
work needs to be understood. It is no lon-
ger enough to hope that people understand
what we are doingwe must tell them and
show them. William J. Sparks , 1965
Sunshine and its conversion into
chemical energy and material through the
pathways of carbon reduction and quantum
conversion in the green plant is our ulti-
mate energy source; it is relatively free of
political control, universally available on an
annually renewable basis, and environmen-
tally clean. Melvin Calvin , 1978
It is a great help to basic chemical stud-
ies if some instrument useful in the basic
or structural studies turns out to be useful
analytically and commercially also; there is
nothing like competition among instrument
makers to develop greater convenience and
sensitivity in instrumentation. Bryce
Crawford Jr. , 1982
The slowing growth for scientific
research ... and the current lack of new
job opportunities are placing great stress
on current graduate and postgraduate
students. Howard E. Simmons , 1994
The change from labor-based manufac-
turing to a knowledge-based manufactur-
ing and service economy is reminiscent of
the transformation from agriculture to the
industrial age a century ago. Mary Lowe
Good , 1997
What lies directly ahead for basic sci-
ence is a period of difficult funding and rela-
tive lack of respect. F. Albert Cotton , 1998
Chemistry, including chemical synthe-
sis, will be a key driver of progress in medi-
cine and human health during the rest of the
21st century. ... Government support of high-
quality research therefore needs to continue
with emphasis on quality and minimization
of political issues. E. J. Corey , 2004
The question of the survivability of
chemistry as a field in its own right has
even been raised. Many people see chem-
ists only as general molecular scientists or
engineers. George A. Olah , 2005
We are at a wonderful time for chemis-
try. It is, I believe, in the position of physics
in the 1910s, just before quantum mechan-
ics made the world impossibly strange, or
biology in the 1950s, just before the double
helix obliterated the old biology. George
M. Whitesides , 2007
For the full source of these excerpts, go
to C&EN Archives, pubs.acs.org/journal/
cenear .
Priestley Medal Addresses
6
LETTERS
American Chemical Society ( C&EN, Jan.
21, page 3 ).
The majority of ACS members work in
industry; a minority work in academia.
The vast majority of ACS awards go to
academia. As one distinguished aca-
demic colleague told me recently, All we
do is get awards. Indeed. Occasionally
an industrial chemist or engineer will win
an award other than the industrial chem-
istry award. Here is the message ACS is
delivering: The best of the best work is in
academia.
I am a 30-plus-year industrial bench
chemist. You know, bench, where actual
chemistry gets done. I tell my colleagues
that a Science paper, the endgame in aca-
demia, is a good start!
Folks, the chemical enterprise provides
actual material solutions critical to soci-
etys needs. To say that only research from
academia is award-worthy is wrong.
Larry Lewis
Scotia , N.Y.
SHALE GASWHY THE RUSH?
THE ISSUE OF EXPORTING natural gas
comes down to how fast we are willing to
hydraulically fracture or frack shale to
get the gas. The faster we go, the cheaper
the gas and the greater will be the urge to
export it ( C&EN, Jan. 7, page 18 ).
I doubt we have any idea how much shale
gas there will be or how long it will last.
Have we learned nothing from the rapid de-
pletion of petroleum that we care not a whit
about husbanding such a one-time bonanza
or considering future generations? Going
slower would also give us time for a better
understanding of all the risks of fracking.
Could it be that the gas industry wants to
rush, not just to make money today, but also
fearing that slowing down would result in a
better understanding of the risks?
Along with precious metals and rare
earths, our political system badly needs
some way to control the rate of consump-
tion of nonrenewable resources.
Victor J. Reilly
Aiken , S.C.
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histories covering the following topics:
Enzyme Inhibition Molecular Modeling
Receptor Binding Assays Chemoinformatics
Hit-to-Lead Process GPCRs
Fragment-based Drug Design Kinase Inhibitors
Lead Discovery & Modification Ion Channels
Structure-based Drug Design Bioisosteres
Drug-like Properties Preclinical Toxicology
DMPK & Protein Binding Clinical Development
William Greenlee, Vincent Gullo and Ronald Doll
Co-organizers
Residential School on Medicinal Chemistry:
Biology and Chemistry of Drug Discovery
June 3-7, 2013
Drew University, Madison, NJ
For more information and application forms:
www.drew.edu/resmed
e-mail: resmed@drew.edu
phone: 973/408-3787; fax: 973/408-3504
LETTERS
continued from page 4
2013 Waters Corporation. Waters and The Science of Whats Possible are trademarks of Waters Corporation.
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9
news of the week
E
NDING MONTHS of speculation, AstraZeneca s
new CEO, Pascal Soriot, last week laid out an
ambitious plan to revitalize the ailing drug com-
pany. The French businessman detailed fundamental
changes to the structure and culture of AstraZenecas
research organization. The company will cut several
thousand research and administrative jobs and focus
R&D on three main areas: respiratory, inflammatory,
and autoimmune diseases; cardiovascular and meta-
bolic diseases; and oncology. Soriot also touted two
partnerships that could signal how the companys de-
velopment pipeline will be rebuilt.
Soriot, who joined AstraZeneca in October from
Roche, faces an uphill battle. The British drug firm is
mired in one of the deepest troughs in the industry. With
fresh generics competition for its blockbuster antipsy-
chosis drug Seroquel and four other drugs, the compa-
nys sales fell roughly 17% last year to $28.0 billion. Ana-
lysts expect that figure to sink to $21.5 billion by 2018.
While contemplating a new strategy, Soriot visited
AstraZeneca sites around the world and found a re-
search organization that had become afraid of taking
risks. We have great people doing great research, but
over the years its fair to say that we lost some of our
scientific confidence, particularly in small molecules,
Soriot told reporters. That will change.
Soriots first move came in January, when he gave two
top executivesR&D chief Martin Mackay and commer-
cial operations head Tony Zooktheir walking papers.
The next move came early last week, with the cre-
ation of three R&D hubs: Cambridge, En gland, where
AstraZeneca will build a $500 million research facility
and headquarters; Gaithersburg, Md., where its biolog-
ics unit MedImmune will house most of AstraZenecas
drug development; and Mlndal, Sweden, which will
continue to focus on small-molecule R&D.
Meanwhile, AstraZeneca is ending R&D at its Alder-
ley Park site in Cheshire, En gland, closing its London
office , and downsizing its Wilmington, Del., site. Over-
all, the changes mean a loss of about 1,600 research
jobs and the relocation of 2,500 others.
On Thursday, Soriot unveiled another 2,300 cuts
to sales and administrative positions. He put all of the
changes in the context of his larger vision for research.
The fragmented footprint in R&D had made it hard
for researchers to collaborate, particularly between
small- and large-molecule teams, he said. And some
sites were too far from bioscience hubs or were not
situated to attract the best scientists.
The decision to invest in Cambridge, En gland, is
based on Soriots belief that the city is one of the rare
places in the world that could potentially compete with
the likes of Boston and San Francisco, he told reporters.
The firms tightened R&D focus does not mean it is
abandoning research on infection,
vaccines, and neuroscience, Soriot
said. But it does mean AstraZeneca
will take a more selective, opportunis-
tic approach to such projects.
Industry watchers are interpreting
the moves as a shift away from tradi-
tional small-molecule drugs. This
appears to be a clear signal of intent
from the new CEO that R&D will
become more focused on biologics,
Morgan Stanley stock analyst Peter
Verdult said in a note to investors. Of
the 40 molecules in AstraZenecas
clinical-stage pipeline, he noted,
about 45% are small molecules and
55% are biologics.
Observers were anxious to hear
Soriots strategy to bring new drugs
into the firms relatively shallow pipe-
line. Although some analysts have
suggested that a large acquisition is
in order, Soriot said the focus will re-
main on small acquisitions, licensing
deals, and tighter alliances with aca-
demia and biotech companies.
To that end, Thursday also
brought news of two new part-
nerships: an expansive deal with
Cambridge, Mass.-based Moderna
Therapeutics to develop messenger
RNA therapeutics and a partnership
with Karolinska Institute to establish
a translational research center on the
Swedish medical schools campus.
The pacts are a first step in what is
sure to be a lengthy rebuilding. Astra-
Zeneca needs to be more aggres-
sive and do more of every kind of
deallicensing deals, partnerships,
and geographic expansionsaid
Michael Latwis, an analyst with the health care consul-
tancy Decision Resources . LISA JARVIS
BIG PHARMA: Thousands of job cuts and
emphasis on three R&D areas highlight
CEO Pascal Soriots revival strategy
ASTRAZENECAS
LEAN NEW LOOK
Soriot
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MARCH 25, 2013 EDI TED BY CRAI G BETTENHAUSEN & SOPHI A L. CAI
GLOBAL SHAKE-UP
Cambridge, En gland: New site for
small- and large-molecule research will
be built for $500 million and become
the companys headquarters.
Gaithersburg, Md.: Existing
MedImmune headquarters will
house most of AstraZenecas drug
development for small and large
molecules.
Mlndal, Sweden: Small-molecule
research site will become the third
major R&D hub.
Cheshire, En gland: Research
activities in Alderley Park will end,
although many of the 1,600 scientists
will move to Cambridge or other sites.
London: Office will close by 2016,
affecting about 350 people.
Wilmington, Del.: Site will lose
about 1,200 jobs as drug development
moves to Gaithersburg.
Stockholm: Integrated Translational
Research Centre for cardiovascular
and metabolic diseases and
regenerative medicine will be created
at Karolinska Institute. Five-year
partnership will involve 2030
scientists and receive $20 million in
annual funding.
Cambridge, Mass.: Partnership
worth up to $420 million with Moderna
Therapeutics will develop messenger
RNA therapeutics for cancer and
cardiometabolic diseases. AstraZeneca
can pick up to 40 drugs for clinical
development during the five-year pact.
10
NEWS OF THE WEEK
H
OW LIGHT OR MOISTURE triggers a plant to
curl its leaves or release its seeds has long in-
spired scientists to strive toward soft synthetic
materials that similarly shape-shift in response to the
surrounding environment. Researchers envision such
substances being used to trigger the activity of drug
delivery or robotic devices.
Some experimental materials have already been
synthesized that deform because of a change in a single
parameter, such as temperature, but they can take only
one of two shapes. Researchers have now taken the
next step: Theyve
programmed a
polymer hydrogel
to adopt multiple
shapes in response
to multiple trig-
gers ( J. Am. Chem.
Soc., DOI: 10.1021/
ja400518c).
We made a hy-
drogel take three shapes, says the University of Toron-
tos Eugenia Kumacheva , who led the team with Zhihong
Nie of the University of Maryland, College Park. But in
general, with our method, we can make it take more.
The work opens the door to more sophisticated
shape-shifting materials than are now available.
To fabricate the shape-shifters, the team exposes
a thin layer of gel made with one type of monomer to
a solution containing another monomer as well as a
cross-linker. The solution also holds a photoinitia-
tor, a compound that jump-starts polymerization in
response to light. After the gel absorbs these compo-
nents, the team places a patterned mask over top of it
and irradiates the assembly with ultraviolet light.
The researchers then rinse away unreacted reagents
and repeat the process with a new mask and different
monomers. The end result is a patterned hydrogel
sheet with myriad microscopic patches that have dif-
ferent rigidities and swelling abilities.
When exposed to a high-pH solution, polymeth-
acrylic acid-rich stripes on a hydrogel sheet swell,
causing the entire film to curl into a long, thin tube.
And at high salt concentrations, the team showed,
poly( N- isopropylamide)-rich patches shrink, leading
to a stubby, wide-bore tube.
Ryan C. Hayward , a polymer scientist at the Uni-
versity of Massachusetts, Amherst, said the work
demonstrates a route to patterning multiple different
stimuli-responsive polymer networks within the same
object. LAUREN WOLF
MATERIALS: Gel sheets adopt 3-D
forms in response to various stimuli
HYDROGELS TAKE
MULTIPLE SHAPES
A hydrogel sheet
patterned with
various types
of polymers
(indicated by colors
in cartoon) takes
different shapes in
response to high
pH and to high salt
concentration.
J
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D
OW CHEMICAL will construct several Gulf
Coast chemical plants and supply raw materials
to a major U.S. facility planned by a Japanese
joint venture. Together, the projects demonstrate how
U.S. investment in chemical manufacturing based on
low-cost natural gas from shale is going beyond basic
commodities to include high-value derivatives.
As several other large chemical producers have
done, Dow already announced plans to build an eth-
ylene cracker on the Gulf Coast. Now, the largest U.S.
chemical maker says it will add several downstream
polymer facilities at yet-to-be-determined locations.
Among the new Dow projects are a low-density
polyethylene plant serving packaging and telecom-
munication markets, an enhanced polyethylene
facility making polymers for packaging and medical
applications, and a facility producing elastomers
for hot-melt adhesives. Dow also restated previous
plans to build an ethylene-propylene elastomer plant.
The new polymer facilities will require up to 3,000
workers at the peak of construction, Dow says. All
of its Gulf Coast projects will employ 5,000 work-
ers during peak construction and support more than
35,000 jobs in the broader U.S. economy, the company
claims.
Dows building boom is a radical shift from just a few
years ago, when it was scaling back its U.S. manufactur-
ing presence and concentrating investment abroad.
Trends in U.S. shale gas have led us to make different
decisions about where and how we invest for global
growth, says CEO Andrew N. Liveris.
Dows Japanese partners, Idemitsu Kosan and
Mitsui & Co. , also see new opportunity in the U.S. They
plan to build a 330,000-metric-ton-per-year linear
-olefins facility on the Gulf Coast by 2016. The plant
will consume ethylene from Dows production grid and
supply comonomers for Dow polymers.
After the flurry of ethylene cracker announcements,
such derivatives facilities are a necessary second wave
of shale-gas-related investments, according to Mark
Eramo, vice president for chemical market insights at
the consulting firm IHS Chemical . Given the U.S. mar-
kets limited capacity to absorb all of the new capacity,
Eramo expects that much of it will be exported to Latin
America and Asia. MICHAEL MCCOY
SHALE GAS: Chemical maker discloses
plans for Gulf Coast polymer facilities
DOW PLANS MORE
U.S. INVESTMENT
Dow will build an
ethylene cracker
at this site in
Freeport, Texas.
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NEWS OF THE WEEK
R
ECEPTORS FOR the neurotransmitter sero-
tonin are distributed throughout nearly every
organ system in the body, and they are the tar-
gets of drugs to treat innumerable problems, including
depression, migraines, and obesity.
Drug designers do their best to craft molecules that
zero in on individual serotonin receptors (also known
as 5-HTs). But at least 14 5-HT subtypes are known, and
many drugs can bind more than one. Thats a problem.
In particular, scientists want to avoid a subtype known
as 5-HT
2B
, which is sometimes called the death recep-
tor because it can lead to life-threatening cardiac side-
effects if unintentionally activated.
Help will come from new crystal structures of 5-HT
1B
and of 5-HT
2B
, each bound to the migraine drugs ergot-
amine and dihydroergotamine ( Science, DOI: 10.1126/
science.1232807 and DOI: 10.1126/science.1232808 ).
The findings provide a blueprint for designing more
selective 5-HT inhibitors.
The team behind the structures includes Raymond
C. Stevens , a chemistry and molecular biology profes-
sor at Scripps Research Institute, La Jolla, Calif.; Bryan
L. Roth , a pharmacology professor at the University of
North Carolina; H. Eric Xu , director of the Center for
Structural Biology & Drug Discovery at Van Andel Re-
search Institute in Grand Rapids, Mich., and Hualiang
Jiang , a professor at the Shanghai Institute of Materia
Medica.
Reaction to the new work has been enthusiastic.
These are the first structures of the large 5-HT family,
which is one of the most important classes in central
nervous system disease, observes Fiona Marshall,
founder and chief scientific
officer of drug discovery firm
Heptares Therapeutics .
This is major news for our
field, adds Kathryn A. Cun-
ningham , a professor in the
pharmacology and toxicology
department at the University
of Texas Medical Branch. The
structures were solved for the
receptor-ligand cocrystals,
which provides important in-
sights into how the receptors
work.
The importance of selec-
tivity was most infamously
illustrated in the 1990s by the
obesity treatment Fen-Phen
(fenfluramine-phentermine).
Both molecules targeted 5-HT
receptors, but they werent
selective enough. Unbeknown
to scientists, they also bound
to the death receptor, 5-HT
2B
,
triggering sometimes-fatal
cardiovascular side-effects.
Fen-Phens withdrawal from
the market was the largest in
history and cost its manufac-
turer, Wyeth, billions of dol-
lars in damages.
From the structures and
simulations, the group discov-
ered that 5-HT
1B
and 5-HT
2B
contain similar main bind-
ing pockets. In addition, 5-HT
2B
has a secondary binding
pocket that is a good match for fenfluramines active
metabolite. And that, they report, is enough to account
for Fen-Phens adverse effect. ELIZABETH WILSON
BIOCHEMISTRY: Crystal structures of
serotonin receptor-drug complexes
could reduce killer side-effects
AVOIDING THE
DEATH RECEPTOR
SELECTIVITY UNVEILED
A computer image shows subtle
diferences in binding-pocket structures
of 5-HT receptors 1B and 2B.
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With the fiscal year half over, Congress
has passed legislation to fund the federal
government through Sept. 30, the end of
fiscal 2013. The measure gives increases
to some key science agencies but leaves
the across-the-board spending cuts, or
sequestration, in place.
The bill, H.R. 933 , passed the Senate
on March 20 by a 73-26 vote and the
House of Representatives the following
day by a 318-109 vote. President Barack
Obama is expected to sign the bill be-
fore March 27, when the current budget
stopgap is set to expire .
The measure includes 2013 appro-
priations bills for defense, military con-
struction and veterans affairs, agricul-
ture, homeland security, and commerce,
justice, and science. The bill would
essentially fund the rest of the federal
government at 2012 levels for the rest of
fiscal 2013.
Under the bicameral legislation, the
National Science Foundations budget
would grow by $221 million, the Food
Safety Modernization Act would receive
implementation funds, NASA would
get a slight increase in its Science Di-
rectorate, and the National Institute of
Standards & Technology would get more
money for its laboratories and technical
research.
This legislation provides funding for
essential federal programs and services,
helps maintain our national security, and
takes a potential shutdown off the table,
House Appropriations Chairman Hal D.
Rogers said after the bills passage. Im
proud that we were able to reach across
the aisleand across Capitol Hillto
produce a meaningful, bipartisan bill.
SUSAN MORRISSEY
BUDGET Congress finalizes 2013 appropriations, avoids government shutdown
12
NEWS OF THE WEEK
G
OVERNMENT SPENDING restraints in the U.S.
and Europe cast a shadow over the Pittsburgh
Conference on Analytical Chemistry & Applied
Spectroscopy (Pittcon), held last week in Philadelphia.
Instrumentation sales executives attending the meet-
ing were cautious about the outlook for 2013.
In the U.S., the month-old sequestration of federal
funds hasnt yet had a direct effect on the
buying behavior of government-backed re-
searchers, Marc N. Casper, CEO of Thermo
Fisher Scientific , told C&EN. However, if
the program continues through the year, it
could have a half-percent impact on sales.
Thats not huge, but it is material, he said.
Executives with small instrument mak-
ers, such as Douglas W. Later, president of
Torion Technologies , are also concerned
about federal budget cuts. About half of
Torions sales of its portable gas chroma-
tography/mass spectrometry instruments
are through Smiths Detection, which
provides them to the U.S. government for detection of
chemical warfare agents and illicit drugs, Later said.
Business is choppy both in North America and in
Europe, where the sovereign debt crisis has pinched
instrument makers, acknowledged Rainer Blair, presi-
dent of mass spectrometry specialist AB Sciex . But
sales in China, where the government recently initiated
a five-year program to improve health care, continue to
be strong, he said.
We have some phenomenal products, but people
dont have the money, said Rohit Khanna, vice presi-
dent of marketing for Waters Corp. Still, he expects
researchers to pony up for the firms new Acquity Ad-
vanced Polymer Chromatography System, developed
with Dow Chemical to improve molecular weight anal-
ysis of polymers. The system replaces the widely used
gel permeation chromatography that Waters developed
with Dow 50 years ago.
Bruker revealed at Pittcon that it has installed the
worlds highest frequency dynamic nuclear polarization-
nuclear magnetic resonance spectrometer, developed
with Massachusetts Institute of Technology, at Utrecht
University in the Netherlands. Scientists will use the
sensitive instrument to study complex biomolecules.
But economic uncertainty has held back wider adop-
tion of the new instrument, said Bruker CEO Frank
Laukien. Because of the political situation, Laukien
said, there has been little uptake of the technology so
far in the U.S., though it is a U.S. outgrowth. MARC
REISCH
PITTCON: Caution is the watchword
among scientific toolmakers
A SPOTTY OUTLOOK
FOR INSTRUMENTS
More than 17,000
people attended the
Pittcon exhibition
and conference in
Philadelphia.
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F
EW TREATMENTS EXIST for retina-damaging
diseases such as macular degeneration and retini-
tis pigmentosa. And the treatments that are avail-
able simply slow progression of these diseases rather
than restore lost vision.
A new polymeric device restores
light sensitivity to degenerated retinas
taken from blind rats, a first step to-
ward stopping and reversing blindness
caused by retinal damage. The device,
developed by neuroscientist Fabio
Benfenati and materials scientist Gug-
lielmo Lanzani of the Italian Institute of
Technology and coworkers, consists of
layers of poly(3-hexylthiophene), indi-
um tin oxide, and glass ( Nat. Photonics,
DOI: 10.1038/nphoton.2013.34 ).
On top of the polymer layer, the researchers placed
retinas removed from the rats. When exposed to light,
the polymer restored light sensitivity to the damaged
retinas as measured by firing of retinal neurons. The
device continued to work for more than a month. The
team hopes to use the polymer for retinal implants,
Benfenati says.
The work is an exciting contribution to the field of
organic bionics, says Gordon G. Wallace of Australias
University of Wollongong, an expert in the integra-
tion of polymers with living systems. He is particularly
enthused about the prospect of being able to tune the
polymers spectral and photoelectric properties.
The current version of the device is aimed at restor-
ing black-and-white vision, but the team hopes to ex-
tend it to colors. Lanzanis group has developed poly-
mers that can discriminate among colors. But he and
Benfenati still need to demonstrate that such color-
sensitive polymers could restore color vision. Doing so
in living animals would also require them to make sure
the brain interprets signals from the device as colors.
Plus, their current device has yet to be used in live
animals. We are testing different substrates for the
polymeric layer to make it suitable for surgical implant
into the eye, Benfenati says. We hope that in four to
five years, provided all in vivo tests turn out positive,
we could start human testing. CELIA ARNAUD
BIOELECTRONICS: Polymeric device
restores light sensitivity to damaged
retinas removed from rats
A VISION FOR
BIONIC RETINAS
Green light hits a
polymer and causes
a rat neuron (~20
m wide) grown on
the surface to fire.
The combination
restores light
sensitivity to
degenerated
retinas.
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13
NEWS OF THE WEEK
U
.S. GOVERNMENT officials say they have made
substantial progress toward resolving prob-
lems with the program for securing the nations
chemical facilities against potential terrorist threats.
But government auditors are raising new concerns.
We are moving forward strategically to address the
challenges before us, Rand Beers, undersecretary of
the Department of Homeland Security (DHS), told a
subpanel of the House of Representatives Energy &
Commerce Committee on March 14. We will continue
to work with stakeholders to get the job done of pre-
venting terrorists from exploiting chemicals or chemi-
cal facilities.
The congressional hearing was held to review the
progress DHS has made over the past year to address
internal problems that have hindered implementation
of the nearly six-year-old Chemical Facility Anti-Ter-
rorism Standards (CFATS) program.
CFATS covers 4,380 high risk facilities that manu-
facture, use, or store threshold quantities of certain
hazardous chemicals.
An internal DHS memo that was leaked to the media
in December 2011 exposed a series of flaws within the
program, including wasteful spending and a failure by
department officials to approve any of the site security
plans that facilities are required to prepare and submit
for review.
Sadly, it has been a very painful process to see
how badly CFATS had fallen short of our expecta-
tions and to see the struggle, both inside DHS as well
as externally, to get the program back on track, said
Rep. John M. Shimkus (R-Ill.), chairman of the House
Subcommittee on Environment & the Economy.
David Wulf, deputy director of DHSs Infrastructure
Security Compliance Division, told lawmakers that his
office has begun to clear a backlog of approximately
3,100 facility security plans, giving preliminary approval
to 261 and signing off on 50 others after completing on-
site inspections. The approval process for the 581 facili-
ties thought to pose the greatest potential security risks
should be complete by May 2014, he noted.
DHS assigns facilities to one of four risk-based tiers,
focusing mostly on
the number of human
casualties likely to
result from a terror-
ist attack. Facilities in
the highest-risk tiers
must meet the most
stringent security
requirements.
But Stephen L.
Caldwell of the Gov-
ernment Accountabil-
ity Office , the inves-
tigative arm of Con-
gress, questioned the
risk-assessment model
that DHS uses to classify facilities, saying the depart-
ment does not consider a plants vulnerability to attack
nor the economic consequences of a successful assault.
As a result, he said, DHSs current approach to assign-
ing chemical facilities to risk tiers is incomplete.
Shimkus said it appears that DHS is evaluating
only part of the threat, not all of it, and he sug-
gested that the tier classification methodology needs
improvement.
Beers said he is confident that the general model
is correct, and he pointed out that vulnerability is ad-
dressed in the site security plans that facility operators
create. This is not a static program, and were looking
for assistance and help to see how we might do a better
job, he added. GLENN HESS
FACILITIES: Federal officials defend
backlogged risk-assessment program
INSECURITY ABOUT
CHEMICAL PLANTS
DHSs Beers (left)
and Wulf testified
about protecting
facilities.
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President Barack Obama has proposed a
$2 billion boost to research funding over
10 years to encourage development of
vehicle-related energy technologies, such
as advanced electric vehicles, fuel cells,
biofuels, and natural gas. The goal, he
told scientists at Argonne National Labo-
ratory on March 15, is to shift our cars
and trucks entirely off oil.
The proposed funding would come
from royalty revenues paid by oil and gas
developers drilling in federal waters of
the outer continental shelf. These fossil-
fuel revenues would go into an Energy
Security Trust, which the President pro-
posed in his State of the Union address
last month. The concept was developed
by a coalition that includes retired
military leaders seeking to enhance U.S.
national security through breakthrough
transportation technologies.
At Argonne, Obama also touched on
his yet-to-be-released budget for 2014.
He said it would include some $40 mil-
lion in research for natural gas produc-
tion, which would be a part of a $375 mil-
lion investment in cleaner energy from
fossil fuels, and a $25 million prize for
the first natural gas combined-cycle pow-
er plant that integrates carbon capture
and storage.
The President also called for changes
to ease oil and gas permitting and de-
velopment on federal lands. Yet he also
urged an end to the century-old mix of
tax breaks and subsidies that benefit oil
companies, a proposal that Congress
has repeatedly refused to support. JEFF
JOHNSON
ENERGY Obama pushes electric vehicle R&D, proposes to pull funds from fossil-fuel royalties
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15
COVER STORY
WHEN SOMETHING GOES WRONG with
the inner workings of the body, we call it a
disease. When things go awry in the minds
fine machinery, we call it madness. Risdon
Slate knows all about that. It has been more
than 25 years since the events that led to his
diagnosis of bipolar disorder. But he has no
trouble recalling them.
In 1986, he was a 26-year-old U.S. proba-
tion officer visiting Miami for training. At
one point, he remembers sitting in his hotel
bar and getting into an argument with a
man whom he perceived was
playing the role of his father. I
actually believed that I was on
the set of Miami Vice and that
I was going to be in an episode
of the TV show, Slate says. The
police got involved, and Slate
told officers that he would not
answer any questions unless
they were posed to him by Son-
ny Crockett, the fictional under-
cover police officer and central
character of Miami Vice.
The retelling is almost comi-
cal, but the consequences for
Slate were anything but. As a re-
sult of his bipolar disorder, Slate
lost his job as a U.S. probation
officer. His wife left him. A few
years later, after a doctor took
him off medication, Slate expe-
rienced a second manic episode,
which led to an arrest (which has
since been expunged) and a bru-
tal physical assault while he was
in jail. A bipolar patient swings
between bouts of maniawhen
a patient can feel irrationally eu-
phoricand depression.
For the past 20 years though,
Slate has managed to keep his
disorder in check thanks to
the drug lithium. Taking the
medication has been the key,
says Slate, now a professor of
criminology at Florida Southern
College. It is essentially saving
my life.
Like Slate, 9 million people in the U.S.
struggle with the disease at some point in
their lives, according to the National Insti-
tute of Mental Health. Although roughly a
dozen drugs are approved to treat bipolar
mania and prevent or delay the onset of
manic or depressive episodes, in many
ways, lithium stands alone. Psychiatrists
often turn to lithiumusually given as the
salt lithium carbonateas a first-line drug
for patients. Its ability to calm the highs of
mania and lift the lows of depression has
been known for more than 60 years. Its
the only medication that demonstrably re-
duces the risk of suicide in bipolar patients.
And its inexpensive.
BUT LITHIUM is not a panacea. The drugs
therapeutic window is very narrowthat
is, its toxic dose is only about two to three
times higher than its therapeutic dose.
Patients who take lithium also need to have
the ion monitored in their blood to make
sure its below toxic levels. And there are
the side effects: tremors, fre-
quent urination, thyroid prob-
lems, weight gain, and, in some
cases, kidney failure.
In the hope of skirting lithi-
ums limitations, scientists are
trying to figure out exactly how
the drug works and, in particular,
hunt down its targets. The idea is
this: Because lithium is an ion, it
hits several different cellular tar-
gets, which is why it has so many
side effects. If scientists can fig-
ure out which of those targets are
responsible for its mood-stabiliz-
ing properties, they might be able
to hit them specifically, using a
small molecule that doesnt have
lithiums downsides.
For some percentage of pa-
tients, lithium really does have
a lot of the characteristics of
an ideal treatment, says psy-
chiatrist Gary S. Sachs, founding
director of the Bipolar Clinic &
Research Program at Massachu-
setts General Hospital. How-
ever, that is a relatively small
percentage of patients.
Other drugs approved to treat
bipolar disorder were originally
developed as anticonvulsants
to treat epilepsy or as antipsy-
chotics to treat schizophrenia.
Thanks to their ability to level
out certain moods, the drugs
have been used to treat bipolar
patients. Its not clear how these
LIMITS OF LITHIUM
It helps millions with BIPOLAR DISORDER, but toxicity problems and side effects have
scientists looking for alternatives by analyzing the drugs mysterious mechanism
BETHANY HALFORD , C&EN BOSTON
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Roughly 9 million
U.S. adults suffer
from bipolar
disorder at some
point in their lives,
according to the
National Institute
of Mental Health.
16
COVER STORY
drugs work either, and they often have more
adverse side effects than lithium. All bipolar
medications carry the U.S. Food & Drug Ad-
ministrations black box warning, Sachs
points out, indicating they carry the risk
of death. Patients arent in a hurry to take
those drugs, he says.
People find the side effects aversive,
so they find ways to go off their medicine,
adds psychiatrist Kenneth Duckworth,
medical director of the National Alli-
ance on Mental Illness.
Scientists dont really know what
causes bipolar disorder, which was
once known as manic depressive ill-
ness. It can strike at any age.
THE DISORDER is unique among psychi-
atric illnesses, Duckworth points out, be-
cause people experience one phase of
it, hypomania, positively. People feel
funnier, sexier, and more energetic,
he explains. They dont want to take
their medication, but they may be on
their way to mania and psychosis.
Doctors split bipolar patients into
two subgroups. Those with bipolar
disorder type I, like Slate, have had at
least one full-blown manic episode.
Patients with bipolar disorder type II expe-
rience hypomania but not mania. Both type
I and type II patients wrestle with
depression, usually for far longer
periods than they experience hypo-
mania or mania.
My depression feels like hell,
says Rebecca Gatlin, a 30-year-old
nursing student who was diagnosed
with bipolar disorder at age 19. You
have to push yourself to do every
little thing, Gatlin says. You put so much
effort into getting out of bed and brushing
your teeth. Everything takes so much ef-
fort that youre so exhausted and you walk
around listless. Youre so exhausted from
the littlest thing.
You know that there are only two ways
to get through itto hang on until it lets up
and things get better or the medicine kicks
in, or you make a plan to end your life, and
thats not really a viable option, Gatlin
says. Youre stuck holding on for life.
When you call depression mild, its sort
of like saying youve had a mild heart at-
tack, Sachs says. The depressive phase of
bipolar disorder can be extremely disabling,
he says, and doctors dont have many phar-
maceutical options for treatment.
In 2007, Sachs and coworkers released
the results of the Systematic Treatment
Enhancement Program for Bipolar Dis-
order, or STEP-BD, the largest federally
funded treatment trial ever conducted for
bipolar disorder. They learned that antide-
pressants are no better at treating bipolar
disorder than a placebo.
So far, the track record of the so-called
standard antidepressants has been terrible
in terms of their ability to treat bipolar de-
pression, Sachs says. None of them have
proven to be effective, even though they
are the most commonly prescribed drugs.
So there is an area of great need to find
novel compounds that would either treat
or prevent depression in bipolar people.
Lithium has a reputation for being mod-
erately effective at treating or preventing
bipolar depression. Scientists know that
lithium displaces magnesium ions and
inhibits at least 10 cellular targets. They
have been able to narrow that range on the
basis of what lithium inhibits at therapeu-
tically relevant concentrations, roughly
0.6 to 1 mM.
One putative lithium target researchers
have been pursuing for decades is inositol
monophosphatase, or IMPase. The enzyme
is part of the phosphatidylinositol signal-
ing pathway. It strips the phosphate off of
inositol phosphate to produce inositol, a
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DRUGS FOR TREATING BIPOLAR DISORDER
NOTE: Drug prices are averaged from three different U.S. geographic regions and vary according to dosage,
formulation, and pharmacy. SOURCE: rxpricequotes.com
Aripiprazole (Abilify)
Approved for acute mania,
prevention of manic recurrence
Class: atypical antipsychotic
Dose: 530 mg/day
Cost: $687970/month
Quetiapine (Seroquel)
acute depression, prevention
of depressive recurrence,
Dose: 200800 mg/day
Cost: $186513/month
Ziprasidone (Geodon)
prevention of depressive recurrence,
Dose: 80160 mg/day
Cost: $259408/month
Carbamazepine (Tegretol)
Approved for acute mania
Class: anticonvulsant
Dose: 6001,200 mg/day
Cost: $15225/month
Lithium carbonate
prevention of depressive recurrence,
Class: antimanic
Cost: $1325/month
Risperidone (Risperdal)
prevention of depressive
recurrence, prevention of
manic recurrence
Dose: 26 mg/day
Cost: $1936/month
Lamotrigine (Lamictal)
Approved for prevention
of depressive
recurrence, prevention
of manic recurrence
Dose: 100400 mg/day
Cost: $1222/month
Asenapine (Saphris)
Dose: 1020 mg/day
Cost: $338683/month
Divalproex (Depakote)
Cost: $1871/month
17
key substance in the biosynthesis of com-
pounds that trigger cellular responses.
There is some evidence that in bipolar
patients the phosphatidylinositol signaling
pathway becomes hyperactive. Inhibiting
IMPase halts the pathway and depletes
inositol. Adding credence to this theory, re-
searchers have fingered inositol depletion
in the mechanisms of two other bipolar
medicationscarbamazepine (Tegretol)
and divalproex (Depakote), also called
valproic acid.
How can we really be sure that lithium
works to treat bipolar disorder by inhibit-
ing IMPase? asks John R. Atack, director
of translational drug discovery at En-
glands University of Sussex. You make a
good inhibitor of IMPase and see if it works
in treating people with bipolar disorder.
In the 1990s, Atack was part of a team at
Merck & Co. trying to do just that. Reckon-
ing they couldnt do any medicinal chem-
istry on an elemental ion, because they
couldnt adjust its
structure, Atack
and cowork-
ers developed
IMPase
inhibitors
based on the enzymes substrateinositol
monophosphate.
Eventually they came up with an an-
tagonist capable of inhibiting the enzyme
at nanomolar concentrations. Polar phos-
phonate groups proved to be crucial to the
compounds ability to bind in IMPases
active site, but the phosphonates kept the
molecule from being bioavailable. To get
enzyme inhibition you need polar mol-
ecules, Atack explains, but those polar
molecules dont stand a very good chance of
getting into the brain at high levels.
The group tried to circumvent the prob-
lem by turning the molecule into an ester
prodrug that could cross the membrane of
the cell. It didnt help. If you inject that
compound into an animal, it just sits there
in a greasy lump, Atack says.
FINALLY, THE TEAM used X-ray crystal-
lography to study IMPases active site.
It confirmed what we already knew. The
active site is very polar and therefore you
need polar molecules to bind in it, he says.
Furthermore, the enzyme has no conve-
nient greasy pockets where something less
polar might do the job. At that point, we
didnt really know where to go next, Atack
says, and the project was shelved. Talking
about his work with IMPase is like talking
about an old girlfriend, he adds.
She took a big chunk of my life,
and I still have affection for her.
Its an unanswered question
whether IMPase would be a good
therapeutic target or not, Atack adds.
Merck put a heroic effort into this and got
nothing out of it. Perhaps it is an attractive
but intractable target.
Since then, scientists have
largely been silent about any
efforts to come up with IMPase
inhibitors. Late last year, however,
a team led by Grant C. Churchill and
Sridhar R. Vasudevan, of the University of
Oxford, in England, reported that the com-
pound ebselen can inhibit IMPase ( Nat.
Commun., DOI: 10.1038/ncomms2320 ).
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Merck IMPase antagonist
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Ebselen
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Ebselen, an anti-inflammatory antioxi-
dant, was originally developed by Daiichi
Sankyo, in Japan, to treat patients who had
suffered a stroke. But the compound was
never marketed and has since come off pat-
ent. Its also part of the National Institutes
of Health Clinical Collectionseveral hun-
dred small molecules that have, to some
extent, gone through the gamut of human
clinical trials and have been found to be
safe, but never reached final FDA approval.
In addition to inhibiting IMPase in vitro,
the Oxford researchers found ebselen has
lithium-like effects in a mouse model of
mania. The compound calms mice that
have taken amphetamine. Subsequent
administration of inositol reverses the be-
havior, Churchill says, which is a clue that
ebselen affects inositol recycling.
Since the report came out, Churchill
says, a few psychiatrists have started to ap-
ply for funds to study ebselens effects in bi-
polar patients. At Oxford, doctors are giving
the compound to a small group of healthy
adults to see how it affects inositol process-
ing in the brain. Ebselen has gone from
identification as a potential bipolar treat-
ment to human trials in about two years,
Churchill points out. That is incredibly fast
for any drug discovery effort.
SOME, HOWEVER, are skeptical that
IMPase is a viable target for making lithium
mimics. The target was discredited years
ago, says Edward M. Scolnick, who served as
president of Merck & Co. from 1982 through
2002. Rather, he believes the key to finding
better treatments for bipolar disorder lies in
unraveling the diseases genetics. Currently
chief scientist at Broad Institutes Stanley
Center for Psychiatric Research, Scolnick is
part of an effort trying to do just that.
The single largest risk factor for a
person becoming bipolar is genetic, Scol-
nick explains. Scientists cant study the
biochemistry of the living human brain, he
points out, and imaging methods lack the
sensitivity to pick up molecular causes. So,
Scolnick says, the only way to get a handle
of the underlying pathophysiology and
biochemistry of bipolar disorder is to find
the genes related to illness and see what
biochemical pathways they point to. Un-
less one understands the underlying bio-
chemistry of the human diseasenot some
animal model that has no clear relationship
to the human diseaseone will never be
COVER STORY
DI SCOVERI ES
How Lithium Became A Drug
Accounts of lithium salts being
used to treat numerous mala-
dies, including those of a men-
tal nature, date back to the
19th century. But John F. Cade,
an Australian psychiatrist, gets
the credit for its discovery as a
treatment for mania.
Cade was a 37-year-old
medical officer working on the
outskirts of Melbourne when
he published his now-famous
1949 report, Lithium Salts
in the Treatment of Psychotic
Excitement, in the Medical
Journal of Australia.
During World War II, Cade
spent three years incarcerated
in a prisoner-of-war camp in
Singapore. There, he came
to believe that there must be
some sort of underlying physi-
cal cause of manic-depressive
illness. There seemed to be no
correlation between the stress
of the camp and who devel-
oped psychiatric illnesses.
Also, when he did postmortem
examinations of patients in
the camp who suffered from
psychiatric illness, Cade dis-
covered they all had some sort
of underlying pathology, such
as a tumor.
Cade hypothesized that
manic-depressive illness was
not unlike thyroid conditions.
In the manic phase patients
had too much of some bio-
chemical while in the depres-
sive phase they had too little.
After Cade returned from the
war, he set up a laboratory in
a converted wooden shed on
the hospital grounds where
he was working. He began a
search for this toxic agent in
the urine of manic patients.
He injected guinea pigs with
urine from patients suffering
from mania, melancholia, and
schizophrenia, as well as with
urine from healthy patients.
The urine of the manic pa-
tients proved to be particularly
toxic. Cade then injected the
guinea pigs with purified ni-
trogen-containing compounds
of urine and discovered that
urea brought about death in
the same way that the urine of
manic patients did.
This didnt explain why the
urine of manic patients was
more toxic than healthy urine
to the guinea pigs, but it set
him searching for chemicals
that could reduce or amplify
the effects of urea. Hed ob-
served that uric acid slightly
enhanced ureas toxicity, but
he had trouble getting the
compound to dissolve in water.
So Cade turned to its
lithium salt. When he injected
guinea pigs with this com-
pound and urea, it diminished
the latters toxicity. Reasoning
that the lithium was respon-
sible, he injected the guinea
pigs with lithium carbonate
and urea and found the same
results. Furthermore, large
doses of lithium carbonate
made the creatures lethargic.
Cade then started taking
lithium carbonate to make
sure the compound was safe.
After convincing himself it
was, he administered the salt
to patients with mania, schizo-
phrenia, and melancholia.
The effect on the patients
with mania was dramatic,
write Philip B. Mitchell and
Dusan Hadzi-Pavlovic, of
Australias University of New
South Wales , in a commentary
on the significance of the dis-
covery ( Bull. World Health Or-
gan. 2000, 78, 515). The first
patient to be given lithium had
long been the most trouble-
some on the ward, but he set-
tled down within three weeks
and was able to leave hospital
12 weeks later. The ion had no
effect on those suffering from
schizophrenia or melancholia.
Cade did not pursue
lithium any further. And, as
Mitchell and Hadzi-Pavlovic
note, its surprising that any-
one took note of his discovery
because it coincided with ac-
counts of lithium toxicity in
cardiac patients in the U.S.
Mogens Schou, a Danish
psychiatrist, and his colleague
Poul Christian Baastrup un-
dertook the research that
would eventually convince the
medical community of lithi-
ums efficacy in treating bipo-
lar disorder. The U.S. Food &
Drug Administration approved
lithium for the treatment of
mania in 1970.
Cades discovery has been
ungenerously described as
serendipitous, and even Cade
himself (a humble and self-
deprecating man) described it
in such terms, write Mitchell
and Hadzi-Pavlovic. Such
comments do not, however,
acknowledge that many sig-
nificant discoveries arise from
keen, curious minds recogniz-
ing the importance of unex-
pected observations during
systematic research.
19
able to make important new therapeutics,
he says.
Scolnick is not the only one to voice
concerns about animal models for bipolar
disorder. Psychiatrist Carlos A. Zarate,
chief of the National Institute of Mental
Healths (NIMH) Section on the Neuro-
biology & Treatment of Mood Disorders,
also notes that these models of the disease
leave something to be desired.
Typically, the complex mental state of
mania is modeled by giving mice amphet-
amines. Scientists test antidepressants
on animals by forcing rodents to swim or
suspending them by their tails. The length
of time the creature swims or struggles is
supposed to be indicative of the antide-
pressants efficacy.
Correlating animal tests that take only a
few minutes with a patient whos suffered
from a disease for decades is problematic,
Zarate says. With such imprecise animal
models and uncertainty about a diseases
pathophysiology, he adds, its no wonder
that companies are hesitant to get into psy-
chiatric diseases.
UNTIL THE GENETICS become clear
enough to show what pathways to pursue,
Scolnick says, he and his colleagues at the
Stanley Center are working on developing
inhibitors of another putative therapeutic
target of lithium: glycogen synthase ki-
nase-3, or GSK-3.
GSK-3 appends phosphate groups to ser-
ine and threonine amino acid residues. It
functions in many pathways and has been
implicated in diseases such as Alzheimers,
type 2 diabetes, and cancer. What it does
in the human brain is very hard to tell, says
Peter S. Klein, the University of Pennsylva-
nia professor of medicine who discovered
that lithium inhibits GSK-3. One possibility
is that lithiums inhibition of GSK-3 turns
on the Wnt signaling pathway, which stim-
ulates the generation of neurons.
Inhibitors of GSK-3 are currently in clin-
ical trials to treat progressive supranuclear
palsy and certain cancers. But there are few
reports of GSK-3 inhibitors being devel-
oped for bipolar disorder.
In 2007, researchers led by Alan P.
Kozikowski, a chemistry professor at the
University of Illinois, Chicago, reported
that 3-benzofuranyl-4-indolylmaleimides
are potent and selective inhibitors of
GSK-3 ( J. Am. Chem. Soc., DOI: 10.1021/
ja068969w ). The most promising of the
compounds Kozikowskis team made
calmed hyperactive behavior in mice that
took amphetaminethe
same model system of mania
the ebselen researchers used.
But Kozikowski says funding
for the project dried up and
his group hasnt worked on
GSK-3 inhibitors for years.
Scolnick says his group at the Stanley
Center has come up with some selective
GSK-3 inhibitors, but he
declined to comment on
their structures. Now, he
says, theyre doing classi-
cal medicinal chemistry
to boost the molecules
pharmaceutical profiles.
Some people are concerned about using
GSK-3 inhibitors, Klein says. Inhibiting
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COVER STORY
GSK-3 potently activates the
Wnt pathway, he says, and ac-
tivation of the Wnt pathway
is a key step in roughly 90% of
colorectal carcinoma. The
worry is that youre going to
cause cancer, he says. In the
many years that lithium has
been studied, there has been no increased
incidence of leukemia or cancers in people
taking lithium, Klein is quick to add, but
a more potent GSK-3 inhibitor could be
oncogenic.
One drug thats recently grabbed the
spotlight for treating bipolar depression
is the anesthetic agent ketamine ( C&EN,
Aug. 23, 2010, page 8 ). In the past
few years, trials in people have
shown that a subanesthetic infu-
sion of the drug can relieve the
symptoms of depression and sui-
cidal urges in a matter of hours, says
NIMHs Zarate, who conducted some
of the studies. The effect lasts about a
week, whereas commonly prescribed anti-
depressants usually take weeks to work.
Ketamine is a derivative of phencycli-
dine, or PCP, and acts as an antagonist of
N -methyl- d -aspartate glutamate receptors.
Theres some evidence that its antidepres-
sant effects may be modulated by GSK-3,
although scientists arent sure how.
Its really ignited interest in drug dis-
covery and development, Zarate says.
His group and others are looking into
compounds that act like ketamine but last
longer and dont have ketamines psycho-
tropic side effects.
Although interest may be picking up,
efforts from the pharma-
ceutical industry to develop
new drugs specifically to
treat bipolar disorder remain
rare. Last year PhRMA, the
Pharmaceutical Research &
Manufacturers of America,
put out a report on medi-
cines in clinical trials to treat mental ill-
ness. Most of the 12 compounds listed for
bipolar disorder fall into the category of
anticonvulsant or antipsychotic. Even the
few that dont fit into those categories were
originally developed for other uses.
New drugs come at a price, though. The
expense of our medication is a problem,
says Leah Nakamura, who has bipo-
lar disorder type I and coordinates
several support groups for people
with the illness. She points out that
having bipolar disorder can make
it tough to keep a job, so people lose
their health insurance and cant af-
ford their medication.
Although lithium costs less than a dollar
a day, drugs still under patent protection,
such as aripiprazole (Abilify), can cost
hundreds of dollars each month. At some
point you just cant afford it, Nakamura
says, and these are lifesaving drugs.
Nakamura wishes she had better medi-
cations to choose from. Shes currently on
her fifth drug to keep her bipolar symp-
toms at bay. If this one doesnt work, she
says, she doesnt have many options, but
she is still hopeful for the future. Naka-
mura says, I tell our young adult support
group, Hang in there. Hope is on the way.
Theyre working on treatments for us.
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20th Anniversary
PORTRAIT OF AN ILLNESS
John Poole, who founded
the bipolarartists.com
website, uses artwork
to cope with his bipolar
disorder. He calls this
piece Inside My Brain.
J
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BUSI NESS CONCENTRATES
SOLAR INSTALLATIONS
HIT RECORD NUMBERS
The U.S. installed a record 3.3 gigawatts of photovoltaic capacity in 2012,
a 76% increase over 2011, according to GTM Research . Of the total, close
to 1.8 GW was part of utility-scale installations, some of which received
Department of Energy loan guarantees. Eight of the 10 largest projects
operating today were completed in 2012. The spike in installations was
spurred by 27% lower costs for solar panel systems, based in turn on a sig-
nificant decline in solar module prices. In the fourth quarter, the cost per
watt of basic solar modules sank to 68 cents compared with $1.15 per year
earlier. U.S. solar growth will slow as utilities approach renewable energy
goals, GTM says, but it estimates that an additional 4.3 GW of installations
will make 2013 another record year. Meanwhile, Japan is expected to boost
solar installations by a whopping 120% to 5 GW of new capacity in 2013,
according to IHS iSuppli . The country has initiated a generous feed-in tariff
as part of a plan to move away from nuclear power. The increase would
make Japan the second-largest solar market after China. MMB
THREE PARTNERS PLAN
SAUDI PHOSPHATE PLANT
U.S. fertilizer maker Mosaic plans to team
up with Saudi Basic Industries Corp.
( SABIC ) and the Saudi mining firm Maaden
to develop a phosphate production complex
in northern Saudi Arabia. The estimated
$7 billion joint venture would include a
mine and a chemical complex making phos-
phate fertilizers, animal feed, food-grade
phosphoric acid, and sodium tripolyphos-
phate. The operation is expected to open in
late 2016 with about 3.5 million metric tons
per year of finished-product capacity. Mo-
saic would contribute design, construction,
and operations expertise plus up to $1 bil-
lion. In exchange, it would get a 25% owner-
ship stake and would market about 25% of
the ventures output. Maaden and SABIC
are already partners in a phosphate fertil-
izer complex on the Persian Gulf. MM
ITALYS ITALMATCH
BUYS PHOSPHORUS
BUSINESSES
Italmatch Chemicals has acquired two
businesses from the bankrupt Dutch
chemical maker Thermphos International.
The deal includes a phosphonates plant
in Newport, Wales, and a phosphorus
chlorides facility in Frankfurt, Germany.
Italmatch says the $100 million per year
in added revenues will bring its sales to
more than $325 million. The Italian firm
adds that the purchase will help it become
a global player in specialty chemicals for
fuels, plastics, water, and detergents.
Thermphos earlier sold its phosphorus
pentasulfide business to ICL Performance
Products. MM
ECOVER PACKAGING TO
USE OCEAN TRASH
Ecover, a company that makes green
household cleaners, will work with Essex,
England-based Closed Loop Recycling to
use plastics collected from the seas around
the U.K. in its packaging. Fishermen in
the region use existing fishing trawls and
new technology to gather floating plastic
debris. Ecovers packages will be made
from a blend of the recycled plastics and
sugar-derived polyethylene as well as high-
density polyethylene made from recycled
feedstock. MMB
BIOBASED MATERIALS
HEAD TOWARD MARKET
Two makers of biobased materials are now
turning out commercial chemicals and
fuels. ZeaChem says it has produced com-
mercial-grade cellulosic acetic acid, ethyl
acetate, and ethanol at its 250,000-gal-
per-year biorefinery in Boardman, Ore.
The firms raw materials are locally grown
trees and agricultural residue. In Colum-
bus, Miss., KiOR says it has made initial
shipments of cellulosic diesel from its
13 million-gal-per-year facility. The firms
feedstock is pine wood chips that fed a
now-closed paper mill. MM
AKZONOBEL REVAMPS
AN OPERATION IN CHINA
AkzoNobel will cut 200 jobs and close two
fatty acid plants in Boxing,
China, and exit the merchant
fatty acid business there.
Akzo obtained the site in 2012
with its acquisition of Boxing
Oleochemicals. The firm will
also spend about $85 million
on its surface chemistry busi-
ness in China. More than half
of the investment will go to-
ward building a multipurpose
reactor for producing amines
in Boxing and improving the
sites environment, health,
LUBRIZOL INVESTS BIG
IN SPECIALTY POLYMER
Lubrizol plans to spend more than
$400 million over the next four years to
expand its business in chlorinated polyvinyl
chloride, a niche polymer used to manufac-
ture hot-water pipes and sprinkler systems.
The first phase of the program includes pre-
viously announced CPVC projects in Texas
and Thailand and a CPVC compounding
plant in India. The second phase calls for
more basic and compounded polymer ca-
pacity in the U.S., Thailand, and India. All
told, the firm will add capacity for 170,000
metric tons per year of the polymer. MM
Closed Loop Recycling sorts plastics
scavenged from the ocean.
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and safety performance. Akzo will use the
remainder of the funds to build an alkoxyl-
ation unit in Ningbo. AS
23
PERSTORP, PURAC EYE
BIOBASED COPOLYMERS
The European chemical companies Perstorp
and Purac are codeveloping caprolactone
lactide copolymers for use in biodegradable
plastics and hot-melt adhesives and as poly-
ols for coatings and adhesives. The partner-
ship will draw on Perstorps skill in specialty
coatings and plastics and Puracs expertise
in derivatives of biobased lactic acid. Our
respective skills and experience comprise a
good foundation for a successful venture,
says Hkan Bjrnberg, Perstorps market
development director. AS
NPS REGAINS GLOBAL
RIGHTS TO GATTEX
NPS Pharmaceuticals has regained world-
wide rights to recombinant human parathy-
roid hormone 1-84 and to Gattex, a therapy
for patients with short bowel syndrome,
from Japans Takeda Pharmaceutical . Take-
da will receive NPS stock valued at $50 mil-
lion and milestone payments over one year
of up to $30 million. NPS had licensed rights
to the compounds outside North America
in 2004 and 2007, respectively, to Nycomed.
Takeda acquired Nycomed in 2011. RM
BIOTECH FIRM GETS
MERCK INHIBITORS
Cerecor , a two-year-old biotech firm based
in Baltimore, has acquired worldwide
rights from Merck & Co. to develop agents
that inhibit catechol- O -methyltransferase.
COMT is an enzyme that breaks down
dopamine. COMT inhibitors, Cerecor
says, could treat central nervous system
diseases such as addictive behaviors and
schizophrenia by increasing dopamine
levels in affected areas of the brain. Under
the agreement, Cerecor will evaluate more
than 2,000 molecules and select candi-
dates for clinical development. MM
AFFYMAX CUTS JOBS
AFTER DRUG SETBACK
Affymax is reducing its workforce by 75%,
or 230 employees, after voluntarily recall-
ing its only product, Omontys, in late Feb-
ruary. The cutbacks include commercial
and medical affairs staff as well as officers
and other employees. Remaining employ-
ees at the Palo Alto, Calif.-based company
will work with its Japanese partner Takeda
Pharmaceutical to investigate the cause of
hypersensitivity reactions and a few fatali-
ties among dialysis patients who received
the anemia treatment. The company is
looking at ways to restructure, sell, or wind
down its operations, including declaring
bankruptcy. AMT
BASF FOCUSES LEATHER,
TEXTILE BUSINESSES
BASF says it will increase the focus of its
leather and textile chemicals businesses
on Asian marketsChina in particular.
The firm will also place a greater emphasis
on high-value-adding applications such
as premium textiles and leather for cars.
As part of its plan, BASF will cut about 65
positions globally, including 29 in Ludwig-
shafen, Germany, but add about 23 staffers
to its operations in high-growth markets
including China, India, and Turkey. Addi-
tionally, the company says it is establishing
BUSINESS
ROUNDUP
HUNTSMAN CORP. has
acquired a 20% stake in
Nippon Aqua, a Japanese
maker of spray polyure-
thane foam insulation. At
the same time, Huntsman
has entered a 10-year
agreement to supply the
company with polyure-
thane systems based
on methylene diphenyl
diisocyanate.
VERSALIS, the chemical
arm of Italian oil company
Eni, has formed a project
with the tire maker Pirelli
to develop tires made
from guayule-based
natural rubber. Earlier
this year, Versalis formed
a partnership with Yulex
to manufacture guayule-
derived rubber.
WILLIAMS COS. is mov-
ing ahead with plans to
build a dehydrogenation
facility in Alberta, Canada,
that will make propylene
out of propane recovered
from oil sands opera-
tions. Set to open in 2016,
the plant will cost about
$900 million and have
capacity for 1.1 billion lb of
polymer-grade propylene
annually.
EVONIK INDUSTRIES
will expand capacity for
Mepron, a coated DL -me-
thionine feed additive for
dairy cows, by one-third by
mid-2013. The company
says high prices for feed
protein are boosting de-
mand for the amino acid.
CLARIANT will invest
about $12 million to build
a plant in Lodz, Poland,
that makes color concen-
trates for plastics master-
batches. The company
says the 73,000-sq-ft fa-
cility will double its capac-
ity for the concentrates.
AMYRIS and Firmenich
have expanded their 2010
collaboration in renew-
able ingredients for the
flavors and fragrances
market. The original pact
called for Firmenich to
fund R&D at Amyris on as
many as three ingredients.
Now, Firmenich will have
exclusive access to Amyris
technology in flavors and
fragrances for up to six
years.
BLUEPRINT Medicines
will work with Wellcome
Trust Sanger Institute and
Massachusetts General
Hospital Cancer Center
to discover novel cancer
targets. The partners will
use Blueprints collection
of kinase inhibitors to in-
terrogate a human cancer
cell line panel created by
Sanger and Mass. General.
MERCK KGaA has hired
Denmarks Nordic Biosci-
ence to help develop spri-
fermin as a treatment for
osteoarthritis of the knee.
Nordic Bioscience will
provide Merck with clini-
cal development services
on a shared-risk basis in
exchange for service fees
and potential milestone
and royalty payments.
SCRIPPS Research
Institute Florida and
Takeda Pharmaceutical
are expanding a research
collaboration formed be-
tween Scripps and Envoy
Therapeutics in 2012.
Takeda acquired Envoy
last November. Takeda will
now draw more deeply on
Scrippss high-throughput
screening facility.
DSM ACQUIRES LIGHT-
TRAPPING TECHNOLOGY
DSM has acquired SolarExcel, a Dutch
company that developed light-trap-
ping technology said to increase the
efficiency of solar panels 612%.
The firms polymer sheet is lami-
nated to the glass cover of a photo-
voltaic module. Its textured surface
guides light toward the modules
active layer, reducing the loss of light
caused by internal reflection, SolarExcel
says. DSM already supplies an antireflec-
tive coating for solar panels. MM
An illustration of SolarExcels light-
trapping polymer sheet at work.
D
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an innovation center for leather and textile
chemicals in Shanghai. BASF expects to
make the changes by the end of 2014. AS
24
PROSPECTS FOR developers of bio-
similars, near copies of off-patent biologic
drugs, look outstanding on paper. By the
end of the decade, patents will have expired
on at least 20 blockbuster biologic drugs
that together have annual sales of more
than $50 billion. Europe, with biosimilars
regulations on the books since 2005, has al-
ready approved several products, and many
other countries are following suit.
But so far, biosimilars are just a tiny frac-
tion of the $160 billion-per-year biologics
market. By 2016 they will still be worth only
about $5 billion in an even larger biologics
business, according to the market research
firm IMS Health . It turns out that getting
biosimilars to market is harder than ex-
pected, especially in the U.S. As a result,
some companies are turning their atten-
tion instead to a class of improved biologic
drugs known as biobetters.
In February 2012, U.S. regulators finally
issued long-awaited draft guidelines for
developers of biosimilar drugs. While the
guidelines answer some questions, they
also leave many aspects of the process to be
determined on a case-by-case basis.
To be approved, a biosimilar must be
shown to be as exact a copy as possible of
an existing biologican untested process
in the U.S. that may prove problematic
because the criteria for demonstrating
exactness are not yet well defined. The U.S.
guidance also isnt clear on whether, like
small-molecule generic drugs, biosimilars
can be prescribed interchangeably with an
approved product.
Lingering regulatory uncertainties,
along with technical and commercial chal-
lenges, have made some developers rethink
their strategy. For example, Israels Teva
Pharmaceutical Industries and its manu-
facturing partner Lonza , as well as South
Koreas Samsung BioLogics , were reported
in late 2012 to have paused clinical devel-
opment of versions of rituximab, a Roche
monoclonal antibody used to treat cancer
and rheumatoid arthritis. Sales of the pat-
ented drug last year were $7 billion.
Roche had been bracing for rituximab
competitors to emerge this year when
patents expire in Europe, but the company
now expects to have the market to itself
until about 2016, Chief Executive Officer
Severin Schwan told analysts in January
during a conference call.
A year ago, Pfizer and Indias Biocon
parted ways as biosimilars business part-
ners, claiming their
priorities diverged. In
2010, Pfizer had paid
Biocon $200 million for
rights to four insulin-
related products. Last
month, Biocon joined
instead with the ge-
neric drug firm Mylan to develop versions
of insulin analogs.
Meanwhile, Merck & Co. , which launched
a biosimilars business in 2009 to great fan-
fare, appears to have pulled back. Last year
it folded the venture into its development
operations to facilitate decision making
and prioritization of resources, according
to a company spokesman. Merck also halted
a multi-million-dollar agreement dating
from 2011 to license a biosimilar form of
Amgen s arthritis treatment Enbrel from
South Koreas Hanwha Chemical .
Changing course again, last month
Merck transferred multiple biosimilar
candidates to Samsung Bioepis , a joint ven-
ture between Samsung and Biogen Idec .
Mercks new partner will take over devel-
opment, manufacturing, and approval,
leaving it with only commercialization. The
deal lets Merck advance several biosimi-
lars while pursuing an internal biologics
pipeline that includes novel, biobetter, and
biosimilar programs, the spokesman adds.
FOR ESTABLISHED biopharmaceutical
firms, the class of biologic drugs being
called biobetters, or biosuperiors, may of-
fer better opportunities and fewer pitfalls
than biosimilars. Thats where the higher
prices and higher margins will be, says
R. Stephen Porter, chief science officer of
Hong Kong-based Dragon Bio-Consultants .
A biobetter is a related or improved ver-
sion of a drugmarketed or a candidate
that is or has been in developmentwith
properties that will allow it to compete on
more than price with older products. Many
biobetters boast new, easier-to-administer
forms or longer half-lives in the body, Por-
ter says. Biobetters may also find use in
different or broader patient groups. In con-
trast, biosimilars offer no clinical advantage
compared with the original drug and may be
surpassed by second-generation products.
Unlike everyday small-molecule generic
drugs, biosimilars and biobetters are ex-
pensive to develop. Sandoz , the generic
drug arm of Novartis, estimates that it takes
seven to eight years and up to $250 million
to make a complex biologic drug and then
prove its similarity to the original in quality,
BIOBETTERS MAY
BE A BETTER BET
Improving on BIOLOGIC DRUGS is an alternative
to taking a more generic route
ANN M. THAYER , C&EN HOUSTON
M
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D
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M
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E
MAKING A
DIFFERENCE
MedImmune
has a program
focused on the
manufacturing
of biobetters.
BUSI NESS
25
structure, and therapeutic effect. Biobet-
ters will take longer and cost even more,
but they are expected to warrant patent
protection and premium prices, rather than
sell at a discount like biosimilars.
MedImmune , the biologics arm of Astra-
Zeneca , has launched a biobetters effort.
The three pillars of our biosuperiors pro-
gram are efficacy, safety, and convenience,
says Steve Coats, senior director for chem-
istry. Applying protein engineering and
other technologies to manipulate proteins
and antibodies will allow us to truly dif-
ferentiate from an existing molecule,
he adds. MedImmunes biosuperiors are
directed at targets validated in at least a
Phase IIb clinical study through to registra-
tion trials and product launches.
Regulators treat biobetters as new mole-
cules that must follow the full drug approv-
al pathway, Coats points out. Even so, going
into the clinic against a validated target
may allow for some streamlining of the de-
velopment process because of preexisting
clinical data. And the odds are better that
the drug will work. The ability to develop a
therapy against a clinically validated target
should reduce the clinical risk, he adds.
ALTHOUGH MANY COMPANIES are try-
ing to develop biosimilars and biobetters,
those most likely to succeed are experi-
enced biologics firms that have technology,
manufacturing, clinical, and regulatory
expertise, industry participants suggest.
These companies are already beefing up
versions of their own and each others
products, such as Roche with new delivery
methods for its rituximab, and using more
modern second-generation manufacturing
methods. For example, Amgen, which is
working with the generic drug firm Actavis ,
uses the slogan Manufacturing matters
as part of its biosimilars efforts.
Manufacturing presents one of the big-
gest obstacles for developers of biosimilars
and biobetters, because small differences
in the cell line, production methods, and
purification steps can alter the final protein
structure as well as its activity and safety.
As a result, regulators have been asking
originator companies to provide biosimilar
developers with details on manufacturing
from their approved drug filings, which
they are loath to share, to help determine
the similarity of follow-on products.
Despite the barriers to entry, the biosim-
ilars field is attracting many new entrants,
according to Deborah Slagle, vice president
for marketing and R&D at SAFC , Sigma-
Aldrichs fine chemicals division and a sup-
plier of cell lines, cell-culture media, and
other products to biologics manufacturers.
The firm has seen an increase in customer
interest for biomanufacturing technologies
and products that can support cost-effec-
tive production. We are seeing a tremen-
dous amount of uptake with our customers
in the Asia-Pacific region, she says, many
of which are Asian companies developing
biosimilars for local markets.
Dragon Bio-Consultants Porter believes
there are going to be some shakeouts as
production quality improves and low-cost
Asian competition emerges. But for now,
biosimilars may likely serve less-regulated
emerging markets while higher-priced bio-
betters find places on Western shelves.
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245
th
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26
CABB MAY NOT BE a major player within
the ranks of the global chemical industry,
but the German firm is a celebrity in Jin-
ing, in northern China, where its the first
foreign chemical maker to set up a manu-
facturing presence.
Earlier this month, the privately held
company signed a memorandum of under-
standing to invest in a local producer of
monochloroacetic acid (MCAA), an inter-
mediate used to make agricultural chemi-
cals and additives for food and plastics. The
investment in China, and a similar one in
India, is part of a corporate plan to become
the global leader in MCAA and to double
overall sales to more than $900 million.
The signing ceremony was a big event lo-
cally, attended by political leaders includ-
ing the mayor and the local secretary of the
Communist Party. Martin Wienkenhver,
CABBs chief executive officer, remarked
that his company had been negotiating
with its Chinese partner, Jining Gold
Power, for a year. We are ready to move on
and set up our joint venture in the biggest
MCAA market there is, he said.
MCAA is a toxic monomer made
through a simple reaction of chlorine with
acetic acid. One of its major applications,
and a target market for CABB in China, is in
the production of carboxymethyl cellulose,
a cellulosic food thickener and personal
care ingredient.
Many companies already make MCAA in
China, but CABB will easily compete with
them, claimed Uwe Brunk, CABBs general
manager for acetyl chemicals, at the event.
CABBs MCAA, he said, is 99.5% pure,
whereas most of the MCAA sold in China
has a purity of 97.5%. Impurities
may be acceptable in certain
applications, but its defi-
nitely not okay when youre
talking about food and personal care, he
told C&EN. The contaminants, which may
include di- and trichloroacetic acid, are dif-
ficult to remove, he added.
AkzoNobel , one of CABBs main compet-
itors in Europe, already produces high-puri-
ty MCAA at a 100,000-metric-ton facility in
Taixing, near Shanghai. Yet the Dutch firm
will not compete directly with CABB in Chi-
na because its customers are primarily mul-
tinational companies operating throughout
Asia, Brunk claimed. CABBs main custom-
ers will be Chinese manufacturers located
in the northern part of the country.
On the whole, the MCAA industry
in both China and India is fragmented,
according to William Bann, business
manager for acetyls and methanol at the
consulting firm Tecnon OrbiChem . Nearly
50 producers operate
in China, but only four
of them can make more
than 20,000 metric tons
per year. India has about
15, mostly small-scale,
producers. Europe and
the U.S. have a handful
of large-scale producers including CABB,
AkzoNobel, and Dow Chemical. Global
consumption of the material is about
725,000 metric tons annually, Bann noted.
Because MCAA is a hazardous sub-
stance, CABBs focus on local customers
makes sense, according to Bann. When
its a dangerous chemical like MCAA that
requires special handling, the users tend to
be located nearby, he said. According to
the market research firm SRI Consulting ,
MCAA is so toxic that mere skin exposure
can result in death.
Once CABBs China venture
is set up, Brunk said, one of the
major priorities will be to up-
grade the sites health, environment, and
safety procedures, with a particular focus
on occupational health. Emphasizing
occupational health is a standard practice
at plants where dangerous chemicals are
handled or produced, he said.
CABB will formally establish itself in
China by acquiring a 67% stake in the MCAA
business of its partner, Gold Power. The
Chinese firm is an electricity generator that
also makes a range of chemicals using calci-
um carbide as a starting material. It operates
a 20,000-metric-ton MCAA plant at a site in
the Jining area where it also makes chlorine.
Gold Power buys acetic acid from a nearby
firm, Brunk said. Like other Chinese pro-
ducers, it uses a batch MCAA process.
After the acquisition, CABB will improve
Gold Powers manufacturing protocols to
CABB SETTLES ON
CHINESE FRONTIER
GERMAN CHEMICAL MAKER establishes its China
venture in a little-known northern city
JEAN-FRANOIS TREMBLAY , C&EN HONG KONG
C
A
B
B

CELEBRATION
CABB acetyls
manager
Brunk (center)
commits the
company to a
China venture.
BUSI NESS
Monochloroacetic acid
OH
Cl
O
27
raise product purity. At a later stage, CABB
plans to build a 25,000-metric-ton facility
that will implement a proprietary continu-
ous chlorination process. The German firm
expects to spend $20 million on upgrading
the old plant and building the new one.
CABBs expansion in China will be over-
seen by Henry Ye, the companys country
manager, who is relocating from Shanghai
to Jining with his family. Ye knows his way
around the government agencies regulating
chemicals in China. Before joining CABB,
he was an administrator of the Taixing in-
dustrial park where AkzoNobel operates.
Whereas demand for MCAA is growing
by less than 2% per year in Europe, growth
exceeds 10% in China and 5% in India. In
India, CABB is also expanding its MCAA
business by acquiring a 76% stake in a pro-
ducer in the northwest city of Ahmedabad.
CABB plans to boost capacity at the Indian
site from 12,000 to 20,000 metric tons per
year to serve Indian and Southeast Asian
markets.
CABBS MAIN MCAA plants are two fa-
cilities in Germany once operated by the
chemical giant Hoechst. As part of a corpo-
rate restructuring, Hoechst spun off its spe-
cialty chemical business, including MCAA,
in 1997 as Clariant . But MCAA was never a
major focus for Clariant, and the company
sold the business to a private equity firm in
2005. CABB, which once stood for Clariant
Acetyl Building Blocks, has since changed
hands twice among private equity firms.
Besides MCAA, CABB also supplies fine
chemicals to the European pharmaceutical
industry ( C&EN, March 26, 2012, page 34 ).
Whereas MCAA had been an orphan
business for Clariant, it is now a core activ-
ity of CABB, according to Brunk. We will
not only sell high-quality MCAA in China,
we will also provide ready-to-use solutions
tailored to our customers needs, he said.
Chinese MCAA producers, he reports, sup-
ply their product in a crystal form that is
more complicated to use than a solution.
The German firm will enjoy strong lo-
cal government support in Jining. At the
signing ceremony, Zhihong Li, secretary
of the local Communist Party committee,
said she will set up a local government sup-
port team to help solve any administrative
problems that CABB may encounter in Jin-
ing. We cant help you with your business
problems, but we can offer support with
everything else, she said.
With friends like that, CABBs foray in
China seems to be off to a good start.
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INDUSTRY CONTINUES TO
QUESTION CANCER REPORT
The federal government used outdated criteria and flawed science to
conclude in a 2011 report that formaldehyde is a known human carcino-
gen and styrene is a reasonably anticipated human carcinogen, represen-
tatives of the chemical industry told members of two National Research
Council (NRC) committees during a meeting last week . Environmental
activists, on the other hand, asserted that industry has a financial inter-
est in discrediting the governments Report on Carcinogens, a biennial
report produced by the National Toxicology Program under the auspices
of the Department of Health & Human Services (HHS). Industry has been
fighting the listing of formaldehyde and styrene in the cancer report for
years and successfully pressured Congress into earmarking $1 million in
the 2012 HHS appropriations to support an NRC review of the listing of
the two chemicals. NRC set up a separate committee for each chemical;
the committees are expected to complete their reviews by August 2014.
In the meantime, industry is urging HHS to stop all work on future cancer
reports. A lawsuit filed against HHS in 2011 by the industry group Styrene
Information & Research Center , for listing styrene in the report, is also
still pending. BEE
HUGE CUT POSSIBLE
IN GREENHOUSE
GASES FROM CARS
By 2050, the U.S. may be able to reduce
by 80% petroleum consumption by, and
greenhouse gas emissions from, light-duty
cars and trucks, according to a report by
the National Research Council . But the
report says a combination of more-efficient
vehicles, increased use of alternative fuels,
and strong government policies would be
needed to meet that goal. Vehicles must
become dramatically more efficient, regard-
less of how they are powered, says Douglas
M. Chapin, principal of MPR Associates
and chair of the committee that wrote the
report. In addition, he says, alternatives to
petroleum, such as biofuels and hydrogen,
must be readily available, cost-effective, and
produced with low emissions of greenhouse
gases. Such a transition would be costly and
require several decades to develop, the re-
port notes. Improving the efficiency of con-
ventional vehicles is the approach that is
most economical and easiest to implement
for saving fuel and lowering emissions, ac-
cording to the analysis. GH
SAFER CHEMICALS
GUIDANCE RELEASED
A coalition of state and local governments
has unveiled draft guidance to help busi-
nesses and government agencies identify
alternative chemicals that are safer than
toxic ingredients. The draft guidance from
the Interstate Chemicals Clearinghouse is
aimed at reducing health risks by encour-
aging the replacement of toxic chemicals
in products and industrial processes with
what it calls inherently safer alternatives.
The document includes suggestions for
conducting assessments of the hazard,
exposure, price, availability, and process
engineering of alternatives but does not
endorse a single one-size-fits-all meth-
odology. The results of the analyses, the
draft says, should distinguish between
alternative chemicals that have clear ben-
efits and those that provide only marginal
reductions in health risks or involve other
trade-offs when compared with the toxic
ingredients . The draft, which is open to
public comment until April 19, was put
together through the Interstate Chemicals
Clearinghouse by environmental regula-
tors from California, Connecticut, Mas-
sachusetts, Michigan, Minnesota, New
York, Oregon, and Washington with a
grant from EPA to the Washington Depart-
ment of Ecology. It is available at http://bit.
ly/16LJYgx . CH
DIETARY SUPPLEMENT
WOES UNDERREPORTED
FDA received 6,307 reports of health prob-
lems associated with dietary supplements,
including vitamins and minerals, between
2008 and 2011, according to a report ( GAO-
13-244 ) by the Government Accountability
Office, the investigative arm of Con-
gress. But FDA may not be receiving
information on all adverse effects
related to such supplements because
industry is required to report adverse
events to FDA only when they are
considered serious. And when adverse
events are not serious, consumers
may not voluntarily report them to
FDA, even when they seek help from
poison control centers. From 2008 to
2010, poison control centers received
at least 1,000 more reports of adverse
events from dietary supplements than
FDA received, GAO found. GAO recom-
mends that FDA explore ways to receive
data related to health effects of dietary
supplements from poison control centers
and provide more information to the public
about such effects. GAO is also urging FDA
to finalize guidelines for industry on new
dietary ingredients and to clarify the dis-
OFFICE OF SCIENCE
HEAD TO STEP DOWN
William F. Brinkman, director of the De-
partment of Energys Office of Science , an-
nounced that he will step down on April 12.
Brinkman has overseen
DOEs almost $5 billion
basic research enterprise,
including 10 national
labs, since June 2009. His
resignation comes two
weeks after President
Barack Obama announced
the nomination of MIT
professor Ernest Moniz
as secretary of energy, re-
placing outgoing secretary
Steven Chu. Brinkman
came to DOE from Princeton Universitys
physics department, and he had previously
worked at Bell Labs and Sandia National
Laboratories. In a note to the Office of Sci-
ence staff, Brinkman said, As I leave office,
my biggest concern remains the erosion of
science funding in the U.S. when most of
the industrialized countries of the world
are increasing funding. AW
GOVERNMENT & POLI CY CONCENTRATES
Brinkman
C
O
U
R
T
E
S
Y

O
F

K
E
N

S
H
I
P
P
/
D
O
E
tinction between dietary supplements and
conventional foods. FDA says it concurs
with GAOs recommendations, but it em-
phasizes that cost is a factor. BEE
30
THE MIDWEST U.S. and parts of Canada
experienced unusually high numbers of
dying honeybees associated with last years
corn planting. The culprit is believed to be
contaminated dust, generated when seeds
treated with neonicotinoid pesticides rub
against each other inside planters that use
air to enable uniform planting of seeds.
Dust is released in the exhaust when seeds
are expelled from the planter to the soil.
To combat the dust problem, the seed
industry is developing new products and
cleaning processes to better ensure that the
pesticides, which protect germinating seeds
from soil pests, adhere to seeds during plant-
ing. A group of stakeholders has also formed
a collaboration to get a better handle on
honey bee foraging conditions around corn-
fields and to test a new lubricant for seeds
that could reduce the amount of pesticide-
laden dust emitted during corn planting.
Called the Corn Dust Research Consor-
tium , the collaboration was formed last
month by the pesticide industry, seed com-
panies, farm equipment manufacturers,
corn growers, beekeepers, conservation
groups, and researchers from academia
and the U.S. and Canadian governments.
Although exposure to pesticide-contam-
inated dust is just one of many factors con-
tributing to honeybee losses, the pesticide
industry and the new consortium hope that
solving this one particular problem will help
reduce the number of honeybee deaths.
Stakeholders involved in the consortium
are optimistic that they will find a solution
to the dust problem in time for the corn-
planting season in April or May 2014. To do
so, they have set an ambitious schedule for
the rest of this year. In particular, the group
aims to accomplish two goals, says Laurie
Davies Adams, executive director of the
Pollinator Partnership , a nonprofit group
that is coordinating the effort.
First, the consortium hopes to recom-
mend best practices for growers to mini-
mize exposure of forager honeybees to seed
dust while maintaining as much forage for
honeybees as possible. To meet that goal,
the group is trying to better understand the
foraging conditions around cornfields at
planting time, Davies Adams notes.
Second, the group is evaluating the
performance of an alternative lubricant
system to minimize
the amount of dust
generated during
the planting of pes-
ticide-treated seeds.
Currently, growers
use graphite, talc, or
some combination
of the two lubricant
powders. Mixed in
with the seeds, such
lubricants reduce seed-to-seed friction
during planting and improve the unifor-
mity of planting. But even with the use of
talc or graphite lubricants, some of the
pesticide active ingredient rubs off treated
seeds during planting.
The consortium has enlisted the help
of government agencies, including the De-
partment of Agriculture, the Environmen-
tal Protection Agency, and Canadas Pest
Management Regulatory Agency , to get
advice on research protocols that will help
the group meet its two goals.
IN FEBRUARY, the consortium sent out a
request for proposals for work related to
the two goals to more than 900 academic
and industrial researchers, and earlier
this month it announced the recipients of
those awards. Altogether, the awards total
$320,000, money that was provided by in-
dustry and nongovernmental organizations.
Progress reports from the researchers
are due in August, and final reports are due
in December, Davies Adams says. Hope-
fully, by January or February we will deter-
mine some possible improvements in corn-
planting best practices, she adds.
Having recognized that bees are being
exposed to pesticides during corn planting,
industry and regulatory bodies are going af-
ter the problem aggressively, says Jeffery S.
Pettis, a bee researcher with USDAs Agri-
cultural Research Service. New technolo-
gies, such as talc replacements, are going to
go a long way toward solving this problem.
Indeed, preliminary results of one new
lubricant, a polyethylene wax developed by
Bayer CropScience , appear promising. At
a Pollinator Summit hosted by EPA earlier
this month, William Hairston, director of
product development for seed growth at
Bayer CropScience, presented data from
laboratory studies on the performance of
CURTAILING
HONEYBEE LOSSES
Stakeholders seek to reduce the amount of pesticide-
contaminated dust generated during CORN PLANTING
BRITT E. ERICKSON , C&EN WASHINGTON
B
A
Y
E
R

C
R
O
P
S
C
I
E
N
C
E
When people actually sit down and talk to each
other, you can come up with some solutions.
LESS DUST Bayer
CropScience plans
to field-test a seed
lubricant system
that reduces
pesticide-laden
dust generated
from corn planters,
such as the one
shown here.
GOVERNMENT & POLI CY
31
the wax. The data show a substantial reduction in total dust and
pesticide active ingredient coming out of the planting unit when
using the wax compared with talc and graphite.
In particular, Hairston reported a 90% reduction in total dust
compared with talc and a 60% reduction in total dust compared
with graphite. With respect to the amount of active ingredient
coming out in the exhaust, he reported a 65% reduction compared
with talc and a 50% reduction compared with graphite.
Bayer CropScience has conducted field trials to test the per-
formance of its lubricant system in New Zealand and Brazil, and
according to Hairston the feedback has been very positive. The
company plans to initiate a large-scale program to field-test the
system on a minimum of 200,000 acres of corn this year in the U.S.
and Canada. The primary objective is to test a wide range of differ-
ent planters in a wide range of geographies where we have different
environmental conditions, Hairston notes.
In addition to alternative lubricants, companies are also develop-
ing new polymers that help pesticides stick to the seed and thus min-
imize the amount of contaminated dust generated during planting.
But the more polymer that is added, the higher the risk of inhibiting
seed flow or germination, says Michael McFatrich, national sales
manager at Becker Underwood , a seed treatment company.
Seed flow is important to monitor because seeds need to move
smoothly through the planter or they wont be placed uniformly
within each row. Uniform spacing leads to higher crop yields.
OTHER COMPANIES are working on ways to condition seeds to
help pesticides stick to them better. Before any polymer or pesticide
is added to a seed, the seed must be clean, says Warren Richardson,
senior marketing manager for seed treatments at DuPont Pioneer, a
seed company. Otherwise, the substance wont adhere well.
DuPont Pioneer uses specialized equipment involving air systems
to remove dust and debris from the surface of seeds prior to treating
them. The process ensures that products applied to the seed stay on
the seed. Clean seed is equal to less dust, Richardson says.
Treating seeds with pesticides and other chemicals is an impor-
tant part of agriculture today, stresses Raymond P. Knake, a con-
sultant in seed treatment R&D. Treating seeds with neonicotinoid
insecticides protects crops from soil insects and other pests. Neo-
nicotinoids also have been shown to improve a plants tolerance to
pathogens, drought, and heat, leading to higher crop yields.
But not everyone agrees that the benefits of neonicotinoid
insecticides outweigh their known risks to honeybees. In late Janu-
ary, the European Commission proposed a two-year ban on the
use of three neonicotinoid insecticides on crops in the European
Union that attract bees. It took that action after the European Food
Safety Authority found significant risks to bees associated with the
neurotoxic chemicals. EU member states, however, failed to reach
a majority for or against the ban during a vote on March 15, thereby
preventing the ban from going into effect.
Meanwhile, bee researchers in the U.S. expect this year to be par-
ticularly bad for honeybees. If I had to predict, total colony losses
in the U.S. will be as high as we have ever seen, USDAs Pettis says.
Nonetheless, Pettis and others are optimistic that at least the
corn dust problem will be solved by next year. A problem was iden-
tified, and we skipped the steps where we pointed fingers at one
another for a couple of years, disputed the research, and sued one
another, Davies Adams of Pollinator Partnership notes. We went
right into a problem-solving mode. When people actually sit down
and talk to each other, you can come up with some solutions.
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32
A POLICY TO restrict travel by federal em-
ployees put in place last year by the White
House Office of Management & Budget
has been unpopular with the science com-
munity from the start, but critics are now
saying it is costing the government more
money, instead of saving it.
The policy requires agencies to cut 30%
of their travel spending from 2010 budget
numbers. Whats more, the directive says
agency travel spending on any one scientif-
ic meeting that exceeds $100,000 must be
approved at the deputy secretary level. And
for meetings exceeding $500,000 in costs,
agency directors must weigh in to deny or
provide waivers for these expenses.
OMB officials say the directive has al-
ready achieved tremendous savings. They
claim $2 billion less in overall government
travel spending in fiscal year 2012 com-
pared with FY 2010. These reductions
have been the result of reducing overall
travel, and also ensuring that required
travel is completed in a cost-effective man-
ner, OMB says.
But a new analysis coordinated by gov-
ernment contractor Battelle Memorial
Institute finds a cost increase for the De-
partment of Energys national laboratories.
According to the analysis, compliance with
OMB travel restrictions has touched off
skyrocketing administrative costs. Battelle
officials tell C&EN that those costs for the
national labs have risen sevenfold, from
some $2 million per year to nearly $14 mil-
lion per year and counting. So the benefits
of the policy, at least in terms of cost, re-
main unclear.
The Battelle and OMB reports on policy
costs are just one part of a so-far genteel
exchange between the Administration and
the scientific community over the impor-
tance of meetings travel for government
scientists. In fact, the scientistslargely
through the efforts of several scientific
societies including the American Chemi-
cal Society, which publishes C&ENhave
embarked on something of an education
campaign for government officials about
the centrality of pro-
fessional meetings
to scientific progress
and the negative fall-
out they see from the
OMB directive.
ACS Director of
Public Affairs Glenn
S. Ruskin says OMB
officials have stressed to the scientific
community that their intent is not so much
to restrict travel as it is to rationalize the
process and ensure that taxpayer money
is spent carefully. Still, he says, scientific
societies have discussed how they might
get amendments to the OMB policy. Now
might be an opportune time.
To cope with the policy, federal scien-
tists and their allies in various scientific
societies have, for example, mapped out
advance planning strategies to understand
whether travel requests for various meet-
ings and conferences will reach thresholds
that require upper management reviews
and approvals. The ultimate goal of these
groups is to do away with or amend mone-
tary caps on federal agency travel spending.
Although the Battelle cost estimates
have not been published, they were com-
piled from actual data gathered by national
laboratories chief financial officers, says
Paul Doucette, director of congressional
affairs for science and technology at Bat-
telle, which is involved in the management
of eight national laboratories, six for the
Department of Energy. Whats more,
Doucette says, the federal government will
be getting the bill for these added burdens.
These are costs we can charge back to the
government.
ALONG WITH THE Battelle data, anec-
dotal evidence from federal scientists and
engineers is that the policy has created
many unintended and negative results.
Many say it has only increased bureau-
cracy, created frustration for those try-
ing to attend professional meetings and
conferences, and placed federal scientists
behind the curve of new understanding
in their disciplines. They worry about the
ability of the government to attract top
scientific talent if the perception is one of
THE ROAD LESS AND
LESS TRAVELED
Policy meant to REIN IN FEDERAL SPENDING may
increase costs, stifle scientific progress, critics say
WILLIAM G. SCHULZ , C&EN WASHINGTON
L
I
N
D
A

W
A
N
G
/
C
&
E
N
Scientific societies have discussed how
they might get amendments to the OMB
policy. Now might be an opportune time.
NO GO Scientific
societies are
leading the charge
to ensure OMB
policy doesnt
hinder scientists
ability to attend
meetings.
GOVERNMENT & POLI CY
33
austerity for career growth and development by public servants.
No one thinks the travel/conference situation is going smooth-
ly, at least not in the DOE laboratory system, says Nancy B. Jack-
son, who is a manager at Sandia National Laboratories in New
Mexico and former ACS president. How can scientists do their
work without collaborating, brainstorming, hearing other views,
and finding out how similar problems are solved? Many highly clas-
sified scientific areas have fallen behind the outside worlds capa-
bilities because of this lack of interaction.
The impetus for the OMB directive was likely a scandal in early
2012 involving employees of the General Services Administration
who spent lavishly on themselves for a meeting in Las Vegas. Al-
though many GSA employees were fired over that scandal, it was
still politically damaging to the White House.
THE CONCERN over the federal travel budget is also shared by
Congress. Legislation restricting government travelnearly iden-
tical to the OMB directivehas been reintroduced in the House of
Representatives. The Government Spending Accountability Act of
2013 (H.R. 313) is identical to a measure introduced last year, but
that bill didnt go anywhere.
To air the issues on travel restrictions for scientists, a subpanel
of the House Committee on Oversight & Government Reform
held a hearing on Feb. 27. There, GSA Chief Administrative Ser-
vices Officer Cynthia Metzler assured lawmakers that GSA has
put in place strict internal travel and conference policies to re-
duce costs, provide strong oversight, and ensure that travel only
occurs when necessary.
But subcommittee members also heard from one of their own
for input about travel restrictions on government scientists: Rep.
Rush Holt (D-N.J.), a Ph.D physicist-cum-politician who extolled
the many benefits of appropriate travel, which can promote col-
laboration and innovation.
As a scientist, I know firsthand how important scientific con-
ferences and meetings are, Holt said. The informal conversa-
tions, as well as the formal presentations and poster sessions that
go into a conference among scientists from different institutions,
lead to new collaborations that have the promise of new discover-
ies. These are not fancy junkets. The obstacles this bill creates
would hinder that kind of collaboration.
Although Ruskin and others maintain that the policy is a real
obstacle for government scientists, budget sequestration may
trump it. Under sequestration, the budgets of all federal agencies
are being reduced. The reduction in available funds is resulting in
agencies scaling back on travel.
The canary in the coal mine, Ruskin says, was an Air Force cost-
cutting plan that surfaced last summer outlining potential budget
reductionsmany of them travel budget deletionsthat would
result if sequestration happened, which it did on March 1.
The first place agencies go is a hiring freeze, a travel freeze
before you have to cut the headcount through furloughs or other
measures, says Ruskin.
Whether through sequestration or travel restrictions, I dont
understand why Congress is so intent upon doing all they can to
drag us down from the number one global position in science and
engineering research, Sandias Jackson says. Maybe they think
American exceptionalism prevents that from ever happening.
Unfortunately, American exceptionalism cannot overcome a lack
of support for science and collaboration among scientific peers.
There are many great countries nipping at our heels.

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SCI ENCE & TECHNOLOGY CONCENTRATES
DNA WEAVED INTO A GRIDIRON
Scientists have a new strategy for weaving DNA into complex nanostruc-
tures, which could find use as tools in crystallography, nanomedicine,
and molecular electronics. Because DNA is robust and its
bases pair up according to strict rules, nanotechnolo-
gists have used the nucleic acid as a building block
for tiny structures. One such building technique,
known as DNA origami, uses short single strands
of DNA to hold a long single strand of the nucleic
acid in a predetermined shape. A group led by Arizona
State Universitys Hao Yan , Yan Liu , and Dongran Han re-
port a DNA origami method that uses short strands to
fasten the long strand into structures that resemble
a gridiron ( Science, DOI: 10.1126/science.1232252 ).
Such wire-frame structures allow the research-
ers to build complex three-dimensional structures that
curve, such as spheres and screws. The basic unit of these
nanostructures is a four-armed junction where two sepa-
rate DNA helices meet, known as a Holliday junction. For the
design to work, the Arizona State team had to deliberately
distort classical Holliday junctions by flipping and rotating the
DNA around the junction point. By varying the length of the
DNA between each Holliday junction, they made the junctions
flexible enough to build curved nanostructures. BH
DRUG TO FIGHT BOTH
INDIGESTION AND PAIN
Drugs to treat gastrointestinal infections
and acute inflammation can interfere with
each other. Chemists in Australia have a
potential solution in a new drug designed
to treat both conditions simultaneously.
The compound, a bismuth acetylsalicylate
complex dubbed bispirin, is the brain-
child of a team led by Philip C. Andrews of
Monash University ( Chem. Commun., DOI:
10.1039/c3cc40645h ). In the fight against
Helicobacter pylori, the bacterium that
causes gastrointestinal troubles that can
lead to ulcers and cancer, chemists have dis-
covered bismuth carboxylate compounds
to eradicate infections. For example, bis-
muth subsalicylate made from
salicylic acid is a prescription
drug that also is the active
ingredient in over-the-
counter products such
as Pepto-Bismol. Acetyl-
salicylic acid, or aspirin, is
one of the worlds most use-
ful pain relievers. One drawback of aspirin
and other anti-inflammatory drugs is a risk
of gastrointestinal bleeding, especially in
people with H. pylori infection. Andrews and
his colleagues wondered whether a single
compound could simultaneously provide
the therapeutic effects of both bismuth
carboxylates and aspirin. They successfully
synthesized bispirin for the first time and, in
initial tests, found that it has bactericidal ac-
tivity as good as or better than current bis-
muth drugs. Studies of the anti-inflammato-
ry activity of bispirin are under way. SR
STRUGGLES WITH
FRACKING WASTEWATER
Energy companies that use hydraulic frac-
turing to extract natural gas use a lot of
process water. Theyre left with recovered
water containing high levels of pollutants,
including benzene, bromide, and the heavy
metals barium and strontium. The firms
can reuse the water, but in some cases they
inject it into deep storage wells or send it to
local treatment plants. A study has found
that water flowing out of treatment facili-
ties still has elevated levels of fracking pol-
lutants ( Environ. Sci. Technol., DOI: 10.1021/
es301411q ). Kyle J. Ferrar and his colleagues
at the University of Pittsburgh analyzed
water leaving three treatment plants in
Pennsylvania before and after the facili-
NANOCALIPERS GET A
GRIP ON NANOTUBES
The properties of single-walled carbon
nanotubes, or SWNTs, vary depending on
the tube size and structure. Most SWNTs,
however, are produced as a mixture. Seek-
ing a way to select specific tubes from this
jumble, researchers led by Naoki Komatsu
of Japans Shiga University of Medical Sci-
ence have developed nano calipers that can
discriminate among SWNTs on the basis
of their diameter, handedness (the way
the tubes twist), and conductivity ( J. Am.
This computer-
generated
model depicts
a nanocaliper
gripping
a single-
walled carbon
nanotube.
A DNA
origami
technique
weaves the
biopolymer
into a
gridiron
pattern, as
shown in this
model.
S
C
I
E
N
C
E
J
.

A
M
.

C
H
E
M
.

S
O
C
.

Bispirin
O
Bi
O
O
O
3
ties complied with a state request to stop
processing fracking wastewater. The team
found that levels of contaminants dropped
significantly after the plants stopped tak-
ing the water. But when the plants still
handled it, concentrations of several of the
chemicals exceeded EPA drinking water
standards. For example, at one facility,
strontium levels were on average 48.3 mg/L,
which exceeds the 4 mg/L standard. Ferrar
says there is no immediate public health
concern over the pollutant concentrations,
but he thinks the elevated levels could af-
fect aquatic ecosystems downstream of the
treatment facilities. JNC
Chem. Soc., DOI: 10.1021/ja312519s ). The
nanocalipers, fashioned from a chiral di-
porphyrin molecule, are an extension, quite
literally, of the groups previous work with
chiral diporphyrin nanotweezers. Nano-
tweezers work well at separating nanotubes
with diameters less than 1 nm, but their
small structural clefts cant pluck out larger
SWNTs. For the nanocalipers, the team put
a carbazole-anthracene-carbazole spacer
between the porphyrins. The spacer makes
the nanocalipers wide enough to accommo-
date SWNTs with diameters greater than
1 nm. The porphyrins and the anthracene
interact with SWNTs via - stacking,
which is how the calipers pluck out tubes
of a specific size. Stereogenic centers at the
peripheries of the porphyrins differentiate
nanotube handedness. Surprisingly, the
nanocalipers also picked out nanotubes
with metallike conductivity over semi-
conducting ones, which the nanotweezers
cant do. BH
35
Tatanan C
OCH
3
OCH
3
OCH
3
OCH
3
CH
3
O
O
OCH
3
OCH
3
CH
3
O
NEW MOLECULAR
WEAPON AGAINST
MALARIA
Malaria takes the lives of some 660,000 peo-
ple each year, according to the World Health
Organization . And because the Plasmodium
parasites that cause the disease have begun
developing resistance to drug treatments
such as artemisinin, new antimalarial drugs
are needed. To add therapies to the pipeline,
a research team led by Michael K. Riscoe
of the Veterans Affairs Medical Center, in
Portland, Ore., has tested the safety and
potency of a quinolone-3-diarylether com-
pound known as ELQ-300 on both malaria
parasites and infected mice ( Sci. Transl.
Med., DOI: 10.1126/scitranslmed.3005029 ).
When the researchers fed infected mice a
1 mg/kg of body weight dose of the drug for
four days, the compound cured the rodents.
A single, lower dose given to noninfected
mice prevented them from contracting ma-
laria from disease-carrying mosquitoes. Like
the antimalarial drug atovaquone, ELQ-300
kills malaria parasites by inhibiting the
enzyme cytochrome bc
1
, which enables the
microorganisms to synthesize DNA build-
ing blocks. We think that ELQ-300 acts
at a different site on cytochrome bc
1
than
atovaquone, however, Riscoe says. This
alternative interaction is likely responsible
for the new drugs heightened ability to
evade the parasites evolving resistance: The
team found that parasites treated with high
concentrations of ELQ-300 developed no
resistant strains over eight weeks, whereas
parasites given atovaquone did so within
30 days. LKW
ANTIDIABETES CLAIM
FOR NATURAL PRODUCT
NOW IN QUESTION
In the search for treatments of type 2 dia-
betes, scientists have been studying mol-
ecules that activate gluco-
kinase. The enzyme cata-
lyzes the first step in the
human bodys breakdown
of glucose and controls
insulin secretion. In
2011, a trio of molecules
named tatanans AC that were puri-
fied from a traditional Chinese
medicine attracted attention be-
cause they appeared to be the first natural
products known to activate glucokinase.
After completing the total synthesis of the
PROTEINS IMAGED IN
MAMMALIAN CELL NUCLEI
The ability to track individual bio molecules
in live cells allows scientists to better un-
derstand the interactions between, for ex-
ample, two proteins or a protein and DNA.
Although methods exist to image single
biomolecules in bacterial cells, imaging
them in larger mammalian cells is challeng-
ing. Harvard Universitys X. Sunney Xie and
colleagues have now developed a fluores-
cence microscopy technique, called reflect-
ed light sheet microscopy, that illuminates
proteins in the nucleus of living mam-
malian cells ( Nat. Methods, DOI: 10.1038/
nmeth.2411 ). The technique involves re-
flecting a thin sheet of light off a mirrora
disposable atomic force microscope canti-
lever coated with aluminumso that the
sheet slices horizontally through the
cell and its nucleus. With the method,
the team can detect fluores-
cently tagged proteins with
nanometer spatial and millisec-
ond time accuracy. In addition, the
imaging can conveniently be carried
out in the same commercially avail-
able glass-bottom culture dishes that are
used to grow the cells. Xie and cowork-
ers demonstrated the technique by imaging
different transcription factors and their
interactions with DNA and each other. JK
IONIC LIQUID HELPS
RECYCLE RARE EARTHS
Rare-earth magnets are indispensable
components in computer hard drives, wind
turbines, audio speakers, and electric ve-
hicles. Because of the insecure supply chain
and price fluctuations of rare-earth metals,
scientists are interested in developing ef-
ficient, safe, and environmentally friendly
methods for recycling magnets to recover
the metals. Tom Vander Hoogerstraete,
Koen Binnemans ,
and coworkers at
the University of
Leuven, in Bel-
gium, have come
up with such a
method, one that
relies on extracting
the metals with an ionic liquid ( Green Chem.,
DOI: 10.1039/c3gc40198g ). A common way
to separate metal ions is by liquid-liquid
extraction of acidic aqueous solutions of
dissolved metal ions with an organic solvent
containing an extraction agent. Rather than
using a volatile, flammable solvent as is cus-
tomary, the Leuven researchers tried ionic
liquids, which are nonvolatile, nonflam-
mable organic-based salts with low melting
points. By using a tetraalkylphosphonium
chloride ionic liquid, which functions as
both a solvent and extraction agent, the re-
searchers separated cobalt from samarium
and iron from neodymium with better than
99.98% efficiency. They focused on those
metal combinations because samarium-
cobalt and neodymium-iron-boron magnets
are two of the most common types of rare-
earth magnets. After the extractions, the re-
searchers stripped the cobalt and iron out of
the ionic liquid so they could reuse it. SR
Vials containing
ionic liquid and
aqueous phases
efficiently separate
transition metals
from rare-earth
metals, as shown
in these before and
after shots.
S
C
I
E
N
C
E
T
O
M

V
A
N
D
E
R

H
O
O
G
E
R
S
T
R
A
E
T
E
ELQ-300
CH
3
O
OCF
3
O
Cl
O
N
H
tatanans, a team is now call-
ing the original result into
question ( Nat. Chem., DOI:
10.1038/nchem.1597 ). Armen
Zakarian and coworkers at
the University of California,
Santa Barbara, teamed with
Brian G. Miller of Florida
State University to take on
the tatanans. They devised
a 13-step route to tatanan A
that used consecutive sigma-
tropic rearrangements to
set three adjacent chiral
centers. They relied on a
different approach to make
tatanans B and C. When they
repeated the 2011 experiments with human
glucokinase and the synthesized tatanans,
they saw no enzyme activation. Its pos-
sible that another natural product was the
glucokinase activator in the original study,
the team speculates, and that it tagged
along with the tatanans during isolation
from the medicinal plant. CD
36
THE PATH TO Cape Flattery is a twisty,
moss-carpeted tunnel underneath red ce-
dar and Douglas fir trees that crowd Wash-
ington states rugged coastline. Micah
McCarty scrambles down the forest trail to
a shoreline below, leaping across tide pools
and slippery rocks to a point where waves
break on shellfish beds. Weve reached the
northwesternmost point of the U.S. main-
land, a craggy tip of the Olympic Peninsula
that belongs to the Makah tribe.
This group of Native Americans has
been fishing and harvesting here for the
past 2,000 years. McCarty, the tribes
42-year-old former chairman, pulls out a
pocket knife and squats down to scrape a
handful of mussels and barnacles into his
hand. We call them slippers and boots,
he says. Ill make them into a Makah paella
tonight.
McCarty and his family grew up pick-
ing these marine delights along the coast.
Oysters, clams, cockles, barnacles, and
other types of mollusks and shellfish have
always been part of the Makah diet, as well
as the tribes culture. The shells are used
both as beads in ceremonial regalia and as
musical instruments. But now, changes in
the global climate have led to rising ocean
acidification that has put in peril the future
of the Makah harvest.
Its already starting to impact the way
that the shellfish cling to the rocks, says
McCarty as he points to a group of boots.
The gooseneck barnacles are a species with
a flexible orange neck that attaches itself
to the wave-tossed rocks. They cant hold
on very well. When the waves hit, you see
theres very few left of that colony.
McCarty isnt a scientist, but his obser-
vations here at Cape Flattery confirm what
marine biologists and chemists are finding
across this region and the globe. Increasing
levels of carbon dioxide in the atmosphere
are reacting with seawater and lowering
its pH. That increasing acidity is damag-
ing shellfish, coral reefs, and other marine
animals.
Over the past 250 years, the average
upper-ocean pH has decreased by about
0.1 units, from about 8.2 to 8.1. This drop
in pH corresponds to an increase in the
acidity of about 30%. Unless things change,
scientists predict the average acidity of the
surface ocean will be more than double
preindustrial levels by the end of this cen-
tury, according to the federal 2013 National
Climate Assessment .
When CO
2
levels in seawater rise, the
availability of carbonate ion decreases.
That change makes it more difficult for ma-
rine organisms to build and maintain shells
and other hard body parts from calcium
carbonate. If the carbonate ion level drops
too low, seawater
corrodes the shells.
The animals have
higher mortality, and
juveniles and larvae
are most at risk. Any
die-off could have
devastating effects
on Washingtons $270 million shellfish and
aquaculture industry.
IN THE PACIFIC Northwest, the problem
of ocean acidification is especially bad for
several reasons. One reason is that prevail-
ing winds push surface waters away from
the coast, causing a local upwelling of
carbon-rich water from the deeper ocean
to the surface. This upwelled water is natu-
rally rich in nutrients, is high in CO
2
, and
has low pH. But now, the upwelled waters
are also carrying an ever-growing load of
human-generated CO
2
picked up from
the atmosphere 30 to 50 years ago when
the water was last in contact with the at-
mosphere. As a result, deep water today is
more corrosive than ever to shell-building
organisms such as oysters, clams, scallops,
mussels, crabs, abalone, and pteropods
(small sea snails eaten by fish and other
marine life).
A separate acidification process is
under way in the vast expanse of Puget
Sound, just as in other estuaries along the
worlds coastlines. Runoff from farms,
storm sewers, and urban pollution flushes
organic carbon and other nutrients into
estuaries that are nurseries to growing
shellfish. These nutrients fuel blooms of
marine algae, which then die, fall to the
bottom, and during decomposition result
in more CO
2
being released to the water.
In the air, emissions of nitrogen and sulfur
oxides from factories, cars, and power
plants are yet another source of nutrients
that cause blooms that lead to more acidic
waters.
The chemical soup resulting from all
of these acidification processes has made
both Puget Sound and the Washington
coastal area among the most acidic water-
ways on the planet, according to Jan
Newton , senior principal oceanographer
at the University of Washingtons Applied
Physics Laboratory.
Because were increasing the anthro-
pogenic contribution of CO
2
, that pushes
the concentrations in the ocean higher and
higher, Newton says. She explains the twin
dilemmas of Washington shell fishersup-
welling along the coast and eutrophication
ACIDIC OCEAN HITS
PACIFIC NORTHWEST
Changes in ocean chemistry threaten Washington states
MAKAH TRIBE as well as the regions shellfish industry
ERIC NIILER , CONTRIBUTING EDITOR
E
R
I
C

N
I
I
L
E
R
NEGATIVE IMPACT
McCarty sees
the results of
ocean acidification
in the barnacles
and mussels
he collects.
SCI ENCE & TECHNOLOGY
37
in the estuariesthat are lowering the pH
of both areas.
The concern is, Will the biology be
more susceptible and change, or is it pos-
sible that some of our outer coast species
will be resilient? Newton asks. Are we at
their threshold? Will we reach it in five or
50 years? Nobody knows that, but the risks
are there.
Newton is directing a network of ocean-
monitoring buoys along parts of the Wash-
ington coast and Puget Sound that are
giving researchers more information about
hot spots of acidity. Shes also working with
the Makah and three other Indian tribes to
serve as eyes and ears to changes already
under way. Some tribal members are help-
ing deploy the massive buoys on
oceanographic cruises, crunch-
ing numbers along with research-
ers and reporting their own data
about abundance of the marine
species they rely on.
Because the Makah and other
tribes have long oral and written
histories of the status of their
surrounding environment, they
have been able to fill in gaps for
researchers such as Newton who
are studying the ocean changes.
Tribal members are providing
scientists anecdotal, yet vital,
data about the abundance of ma-
rine organisms like clams, mus-
sels, and other shellfish that they
have harvested for generations.
TURNING OBSERVATION into
action on this issue is a bigger step, ac-
cording to Chad Bowechop, director of the
Makah tribes marine resources commis-
sion. We are seeing certain things around
here, he says. Weve recognized that
some of our mussels and boots arent as
plentiful around Cape Flattery. The biggest
question is, What can we do about it?
The problem hit home a few years ago
for Washingtons commercial shellfish
growers. From 2005 to 2009, billions of
oyster larvae died in hatchery tanks, which
are filled from the ocean. At first, growers
in Oregon and Washington thought the
problem was a killer bacterium, but re-
searchers finally figured out that the ocean
chemistry was to blame. The increased
CO
2
levels in the seawater prevented the
larvae from building the calcium carbon-
ate body parts they need to grow and live.
As the extent of the damage became
known, political leaders in Washington
grew worried. The states shellfish indus-
tryoysters, clams, and musselsac-
counts for $270 million in direct sales.
And any damage to shellfish or other small
shell-building organisms would also hurt
the larger salmon-based seafood industry,
which contributes $2.4 billion and 42,000
jobs to the regional economy, according to
state figures .
Policymakers have known for several
decades that acidification would likely be
a problem sometime in the future. Theyve
been tracking problems on coral reefs,
for example, in other parts of the world.
But many in the Pacific Northwest were
surprised by the sudden oyster hatchery
die-offs.
Scientists predicted the ocean chem-
istry would change and there would be
impacts, but I dont think they anticipated
it would happen this soon, says Hedia
Adelsman, executive policy adviser for the
Washington State Department of Ecology .
After the oyster larvae disaster, then-
governor Christine O. Gregoire appointed
a blue-ribbon panel to come up with policy
recommendations to prevent an economic
collapse. The final report released in No-
vember 2012 called for a mix of local and
global solutions, research, and action.
Before leaving office in January 2013, Gre-
goire signed an executive order directing
$3.3 million to help shellfish hatcheries keep
their water-monitoring devices operating,
to create an acidification research center at
the University of Washington, and to begin
cutting pollution into Puget Sound. The
plan also calls on the federal government
and Congress to do more to control carbon
emissions that are causing acidification.
Conservation groups applauded Gre-
goires action, which they say is the stron-
gest so far in the U.S. The Ocean Conservan-
cy s Julia Roberson says that absent any help
from the Congress or the White House on
climate change, its up to individual states
to take the first steps. The 158-page report
issued by Gregoires blue-ribbon panel is a
road map for local action on ocean acidifica-
tion that hopefully other states can pick up
and use, Roberson says.
IN THE TRIBAL TOWN of Neah
Bay, just five miles from Cape
Flattery, the Makah hope the
road map isnt coming too late.
Unlike commercial shell fishers,
the tribes 1,200 or so members
cant pick up and move their
harvesting areas outside the
boundaries of their existing res-
ervation. So any environmental
change along their protected
stretch of coastline hits them
particularly hard.
Many Makah families fish for
salmon and other commercial
species from the port at Neah
Bay. They also eat shellfish and
collect shells for tribal cer-
emonies several times a year.
Artisans rake the sandy beaches for the
olive shells that they transform into color-
ful necklaces, headbands, and other regalia
important to the tribe. Some worry that the
shells might not be around in the future.
Its hard to imagine that would hap-
pen, says Janine Ledford, director of the
Makah Cultural & Research Center. We
just take it for granted that olive shells have
always been here and always will be.
For his part, McCarty says the tribes
great strength is its ability to adapt. In
recent years, the tribes natural resources
have been threatened by oil spills, overhar-
vesting, and illegal poachers supplying the
Asian seafood market.
Weve been adapting to these chal-
lenges for a long time, McCarty says as
he stands on the rocks looking across the
Pacific Ocean. We are resilient people
and we keep our dependence on what we
know.
Watch Micah McCarty use his trusty pocketknife to gather
shellfish on Cape Flattery at http://cenm.ag/mkh .
VIDEO ONLINE
ALL DIRECTIONS A variety of sources contribute to the
acidication of marine waters.
A
D
A
P
T
E
D

F
R
O
M

W
A
S
H
I
N
G
T
O
N

S
T
A
T
E

B
L
U
E

R
I
B
B
O
N

P
A
N
E
L

O
N

O
C
E
A
N

A
C
I
D
I
F
I
C
A
T
I
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N
Emissions:
NOx, SOx, CO
2
Point source
Stormwater
runof
Stormwater
runof and
erosion
Crops
River
River input
Erosion
runof
Ocean Upwelled water from deep ocean
38
SCI ENCE & TECHNOLOGY
CLOSE TO 1,500 CHEMISTS convened
in Berlin on March 12 to celebrate the 125th
anniversary of the German Chemical So-
cietys journal Angewandte Chemie. Now
published by John Wiley & Sons, it began
in 1887 as a technical magazine for German
industrial chemists. Today it is one of the
most respected journals for molecular and
material scientists.
The daylong birthday fest
featured music from a saxo-
phone quartet as well as talks
and accolades by more than
a dozen renowned chem-
ists. Today we celebrate a
great event, said Ahmed H.
Zewail , a chemist at Califor-
nia Institute of Technology
who won the Nobel Prize in
Chemistry in 1999.
George M. Whitesides , a
Harvard University chemist,
added praise for the jour-
nals longtime editor, Peter
Glitz . A great journal is the
reflection of a great editor,
he said. Whitesides com-
mended Glitz flexible defi-
nition of what constitutes chemistry and
his willingness to publish interdisciplinary
molecular science. Glitz also introduced
peer review to the journal.
Glitz, who has been the journals
editor-in-chief since 1982, is widely ac-
knowledged as the man behind Angewandte
Chemie s progression from a publication
that primarily printed
German research results
to one featuring impor-
tant chemical discoveries
from around the world.
Its fair to say that there
has been a complete
transformation of this
journal due to Peter Glitz, Zewail said.
When I was a grad student in the late
80s Angewandte was already a marquee
publication, but we primarily thought of
it as a place where Europeans published,
said Carolyn R. Bertozzi , a chemical biolo-
gist at the University of California, Berke-
ley. But by the time I started my indepen-
dent career in 1996, Angewandte was a place
where American chemists also published
their work, she said.
Glitz took over the helm of Angewandte
Chemie just after turning 30, freshly home
from a postdoc position in the U.S. My
vision was to attract the best chemists
throughout the world to publish in Ange-
wandte , Glitz told C&EN. In his office,
he hung a big map of North America, which
he used to mark the origins of the few
manuscripts that trickled in from the U.S.
and Canada in the early 80s. There were
too many empty spots for his taste. I was
convinced that scientific publishing should
be international. That is, Europeans should
publish in American journalsand this
was the case at the timeand Americans
should publish in European journals, which
was not the case. This has changed, and
today Asia has also a major role.
ONE OF THE FIRST steps toward inter-
nationalization prior to Glitz tenure was
the launch of Angewandte
Chemie s English edition in
1962. This move took place
under the editorial watch of
Wilhelm Foerst, a compli-
cated figure in the journals
history.
Foerst, a Nazi Party
member, took the editorial
helm in 1933 and did not
prevent Angewandte Chemie
from providing space for
criminal National Social-
ist (Nazi) ideology, wrote
Glitz in an editorial mark-
ing the journals anniversary
issue in January. Like many
publications during the
Nazi era, Angewandte Chemie
did not publish articles by
ANGEWANDTE S
125TH ANNIVERSARY
Chemists from around the world gather to fete the
German Chemical Societys PREMIER PUBLICATION
SARAH EVERTS , C&EN BERLIN
S
A
R
A
H

E
V
E
R
T
S
/
C
&
E
N
BERLIN BASH
A coffee
break during
Angewandte
Chemie s 125th
anniversary
symposium.
Published articles
0
500
1,000
1,500
2,000
2,500
3,000
90 90 50 60 70 80 40 30 20 1900 10 2000 10
1 2 3 4 5 6
1 World War I (191418)
2 Beginning of the Third Reich (1933)
3 World War II (193945)
4 English version launched (1962)
5 Peter Glitz becomes editor-in-chief (1982)
6 Peer review introduced (1980s)
SOURCE: Mario Mller, Wiley/ Angew. Chem. Int. Ed.
HISTORICAL INDICATORS The number of Angewandte
Chemie articles published per year reects wider political events
and changes to the journal.
39
SO PUNNY!
From tributes to 1980s
pop band the Bangles
(Just another Mannich
Monday) to risqu refer-
ences (Metal mnage
trois), much has been
said of the funny kickers
that grace the abstracts
of papers in Angewandte
Chemie.
The brains behind the
humor range from giddy
journal editors to zeal-
ous authors. A recent
submission on photo-
chemistry paid tribute
to Pink Floyds Shine on
You Crazy Diamond, ac-
cording to Editor-in-Chief
Peter Glitz.
When news of the jour-
nals anniversary party
broke on Twitter, Matthew
Hartings, a chemist at
American University who
tweets as @sciencegeist,
asked about a chemical
pun-writing contest. His
question launched a short
Twitter pun competition
about the party. Contribu-
tions included 125 year
self-assembly process
and Activation barrier for
self-assembly reduced by
cake.
Jewish scientists, printed offensive adver-
tisements, and was full of unbearable lan-
guage, said Franois Diederich , chairman
of Angewandte Chemie s editorial board and
a chemist at the Swiss Federal Institute of
Technology, Zurich.
The only year Angewandte Chemie was
not published was 1946, as Germany
grappled with the end of World War II. This
missing year is why the journal is celebrat-
ing its 125th anniversary on the 126th year
after the first edition: because 2013 repre-
sents the 125th year Angewandte Chemie was
actually published.
IN ANTICIPATION of the anniversary,
Diederich penned a history of the jour-
nal ( Angew. Chem. Int. Ed., DOI: 10.1002/
anie.201300056 ). He spent three hours
each day for six months browsing through
all archival issues of the publication, which
was initially named Zeitschrift fr die che-
mische Industrie (Magazine for the Chemical
Industry) and went through a handful of
other name changes before becoming An-
gewandte Chemie (Applied Chemistry).
When I started the research, I was
under the impression that the publication
was just going to be about industry and
technology in its early years, Diederich
said. Instead, the archives were a treasure
trove of material about the history of
chemistry in Germany and abroad. He at-
tributes the publications breadth to the
fact that when it launched, not much infor-
mation was available except through the
printed word.
He found full issues in the 1880s devoted
to the new area of wine science, obituaries
of famous people such as Alfred Nobel and
Dmitri Mendeleev, and unexpected news
reports from high-profile chemists, such as
the one by Fritz Haber about photochemis-
try he had seen at the Worlds Fair in Paris
in 1900.
Diederich said even in its early days the
journal reported on American innovations,
such as 1904 articles about Niagara Falls
power generation and about American
beer factory technology. At that time, most
breweries in Germany were still family or
monastery operations.
Whitesides, who delivered a plenary lec-
ture at the anniversary symposium, noted
that he had actually begun reading the jour-
nal as a graduate student in the 1960s. Even
before the English edition, many people
who didnt understand German would just
look at the figures in articles. Thats the
great thing about chemistry. You can just
read the pictures even if you dont under-
stand the language, he added.
Cornell Universitys Roald Hoffmann ,
another plenary lecturer at the celebration,
said he was introduced to the publication
around the same time by his longtime
collaborator and fellow Nobel Prize win-
ner, Harvards Robert Burns Woodward .
Together they published the longest article
in the journals history, which took up an
entire issue and which featured some of
the first color images in the publication. In
the figures, negative and positive orbital
lobes were distinguished by blue and green,
Diederich said.
In fact, Angewandte Chemie s use of color
in figures, cover images, and graphical
40
abstracts has long
distinguished the
journal as a leader
among chemical
publications, Stuart
Cantrill , chief editor
of Nature Chemistry,
told C&EN. There
is no doubt that many of the publishing in-
novations pioneered by Angewandte have in-
spired other journals, added Cantrill, who
was not in Berlin for the celebration.
That the journal continues to thrive and
prosper is a credit to its reputation for edito-
rial rigor and uncompromising scientific
integrity, Madeleine Jacobs told C&EN.
Jacobs is the executive director and chief
executive officer of the American Chemical
Society, which publishes C&EN, and was
also not in Berlin. We salute the current
editor-in-chief, Peter Glitz, for upholding
that fine tradition of excellence and send all
best celebratory wishes for this remarkable
anniversary and for continued future suc-
cess, she added.
Or as Helmut Schwarz , a chemist at Ber-
lins Technical University and president of
the Alexander von Humboldt Foundation,
said at the fete, Lang lebe Angewandte Che-
mie . Long live Angewandte Chemie .
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TIME CAPSULE
The late Nobel
Prize winner and
Harvard chemist
Woodward at his
desk with a copy of
Angewandte Chemie.
A
N
G
E
W
.

C
H
E
M
.

I
N
T
.

E
D
.

41
GABRIELA C. WEAVER doesnt lecture to
her general chemistry studentsat least
not in class. She records short lecture snip-
pets that the students watch online before
showing up. During the class period, the
students work problems while the Purdue
University chemistry professor wanders
around the room, observing students,
answering their questions, and looking for
concepts that are giving them trouble.
Weavers strategy is part of a growing
trend called inverted instruction or flipped
classrooms. In this approach, professors
deliver lectures or other class content over
the Web via prerecorded videos during the
time students would traditionally be do-
ing homework. During the scheduled class
time, students work on problems, either
alone or in teams.
The whole idea of flipping the class-
room and putting most of the content
delivery outside of class time is that it frees
up class for other stuff, says physicist
Robert J. Beichner of North Carolina State
University. You can have the students do-
ing things that are more complex, more re-
alistic, because theyve got an expert there
to help them and their teammates to assist
them. They get opportunities to practice
more in-depth problem solving.
The trend has gained steam as more and
more universities experiment with massive
open online courses, or MOOCs. Offered
through providers such as Coursera , a com-
pany started by Stanford University profes-
sors, and edX , a joint venture of Harvard
University and Massachusetts Institute of
Technology , these free online courses give
professors the chance to teach exponen-
tially more students than those who attend
their on-campus classes. Those who have
already flipped their chemistry classes are
using the experience to create such online
courses. Others are getting into the busi-
ness of creating such chemistry MOOCs
as a way to produce the materials needed
to flip their on-
campus classes.
Many flipped
classrooms, in-
cluding Weavers,
are using an active-
learning approach
Beichner designed in 1997. Beichner cre-
ated the approach to fit large classes, where
active-learning methods used in smaller
classes might be unworkable. In Beichners
model, students work at tables in teams of
three or four.
Weaver has used Beichners approach
to flip Purdues general chemistry class for
chemistry majors, which enrolls 5080 stu-
dents. Shes found that even when students
meet only once every two weeks, learning
outcomes benefit.
CURRENTLY, THE NEW approach is in its
third iteration in second-semester general
chemistry. Weaver taught the course in
spring 2011, and Mary J. Wirth taught the
course in spring 2012, using Weavers re-
corded materials, while Weaver was on ma-
ternity leave. For the first two iterations,
the American Chemical Society exams
were used to normalize student perfor-
mance between the conventionally taught
first semester and the flipped second se-
mester. Both times student performance
improved significantly from the first to the
second semester.
Im convinced that students are getting
a better experience by coming to class and
doing this high-impact type of experience,
Weaver says. In the future shes hoping to
replicate the experience in the far-larger
general chemistry class that other stu-
dents, such as engineering or premed stu-
dents, take.
Jeffrey S. Moore , a chemistry professor
at the University of Illinois, Urbana-Cham-
paign (UIUC), is taking a similar hybrid
approach for his organic chemistry classes,
mixing online content delivery with in-class
problem solving. The monologue we de-
liver is just not an effective way of learning,
he says.
Instead of assigning passages from a
textbook for homework, he asks students to
watch five or six five-minute webcasts. Stu-
dents then choose among coming to an in-
class problem-solving session, joining the
FLIPPING CHEMISTRY
CLASSROOMS
Professors SHIFT LECTURES ONLINE to free up class
time for more effective learning activities
CELIA HENRY ARNAUD , C&EN WASHINGTON
U

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F

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Were tricking the students into spending twice as much
time on the material as they would have otherwise.
WORKING PROBLEMS
Cramer helps his
computational
chemistry students in
the computer lab.
EDUCATI ON
42
EDUCATI ON
session remotely, or watching a recording
later. He can offer so many options because
he uses an electronic problem-set package.
All we ask is that they show up to the
exams able to demonstrate that theyve
mastered the ability to solve the kind of
problems weve been teaching them at the
level we expect, Moore says. To encour-
age students to join the problem-solving
discussion in real time, Moore ends each
period with a timed and graded pres-
sure point problem that mimics an exam
setting. He observes equivalent student
performance with most of the options. Stu-
dents who regularly choose to watch the
recorded session are the exception.
Moores webcasts are currently being
used in a Coursera MOOC on introductory
organic chemistry . Moore was slated to be
the instructor, but hes taken a backseat
role to UIUCs Nicholas Llewellyn because
he has become interim head of Illinois
chemistry department.
In the MOOC, we dont have this struc-
tured discussion period where were just
working problems, Moore says. Were of-
fering our problems, but the problems are
going to be solved with a discussion board
as the only means of interacting and asking
questions.
TOTAL OFFICIAL enrollment for the or-
ganic MOOC is around 17,400 students, but
only about 9,000 watched the first video.
Participation continued to drop. The fifth
week ended with about 1,000 watching that
lesson and about 750 taking the associated
quiz. Llewellyn expects the current active
students to complete the course.
Llewellyn attributes much of the attri-
tion to unrealistic expectations. Students
expect a MOOC to be accessible not only
in terms of being free of charge to all com-
ers but also in terms of being approachable
without specialized knowledge or technol-
ogy, he says. Teachers need to clearly
manage this expectation in advance by
enumerating in detail what skills and
knowledge students will need to already
have before beginning the course.
Other professors have joined the rush
of MOOCs because theyre interested in
creating online materials that they can use
to flip their bricks-and-mortar classes.
Michael J. Cima of MIT ran the first
MOOC version of his course Introduction
to Solid State Chemistry (3.091 in MIT
parlance) last fall on edX. A second offering
started Feb. 5 and is slated to run through
June 3. Its the same course he teaches to
MIT freshmen. His course materials include
single-concept videos that follow a learn-
ing sequence. At the end of the sequence,
students answer machine-graded questions
about the concepts. Students can also par-
ticipate in chat rooms on various concepts.
Registrants topped 28,500 for the first
iteration, with more than 2,148 finishing
with enough mastery to earn a certificate,
Cima says. What these numbers dont
indicate is that more than 15,000 students
used the course material through the
course, he says. We believe they used the
material to supplement an existing course
they were taking. More than half were
students at other colleges and universities,
and almost 10% were high school students.
The student outcomes were equivalent
to Cimas regular class. I was mostly skepti-
cal of the online assessments, he says. But
I think I have data to support that online
assessment may be better than the current
written, timed examinations I do in class.
Cima is working to figure out how to
incorporate the online materials in his MIT
class when he teaches it again next fall.
This is going to change how I teach, or at
least how I conduct, the 3.091 class here
next year, Cima says. The students will
have online content. Theyll be marching
through these sequences, and I will spend
more time in my lecture being able to take
questions and do problems. It will be a
much better class.
Vicki L. Colvin is another professor us-
ing a MOOC to get materials for flipping
her on-campus class. When Rice University
was looking for professors to do MOOCs,
Colvin volunteered. Ill have all my videos
and can flip my classroom, she says. That
was my motivation.
Colvin had been working her way toward
flipping her analytical chemistry class for a
couple of years. Her students had varying
levels of preparation. The course meets
twice a week for traditional lectures, but
she added an optional weekly problem-
solving session, which quickly became the
most popular session of the class.
It was stunning, she says. Youd give
a lecture, and then youd show up for the
flipped session. It was like you didnt give
the lecture. They learn it when they do it,
not when they hear it.
Colvin next tried to incorporate more
problem solving into her regular sessions,
switching between short lectures and prob-
lem solving. I realized that wasnt working
so well because it required them to shift be-
tween passive and active learning, she says.
She decided to plunge into a fully flipped
classroom, and the call for MOOCs gave
her just the push she
needed to create her
online materials.
Colvins analytical
chemistry MOOC starts
in May. She admits that
her class is unusual for
a MOOC, most of which
are introductory-level survey courses. Col-
vins class is the same one she teaches to
juniors at Rice. More than 9,000 students
have already registered for the Coursera
version, but Colvin will be satisfied if
100 students finish the course.
This class isnt for everybody, she says.
If you dont know freshman chemistry,
you really cant take my class.
Colvin and Cima have both found that
converting their traditional lectures into
video lectures suitable for MOOCs isnt as
straightforward as they thought.
I had a full set of lectures from four
years of teaching this class, Colvin says.
WANDERING
PROFESSOR
Weaver answers
student
questions
during a
flipped class.
The whole idea of ... putting most of the
content delivery outside of class time is
that it frees up class for other stuff.
43
Its a 30-hour-a-week project for me to design my lectures for this
new platform. The challenge is that she needs to break the lectures
into five- to 10-minute chunks. I probably spend 75% of my time on
the content and thinking through how to teach it, how to chunk my
lectures. The rest of the time she spends on technical aspects like
lighting and sound. She produces her own videos.
IN PREPARATION for the MOOC, shes been using the videos in
her Rice class this term. Because this is the first time Colvin has
moved all lecture materials online, she worried that her videos
might not be up to snuff. She decided not to require students to
watch the videos before class, in case she stopped midsemester for
some reason.
Shes learned from the experience. You have to require them to
watch the videos beforehand, she says. Once I have my stable of
videos next year, theyll be able to watch any video they want, any-
time they want.
Colvin feels that shes reaching a swath of
the class she wasnt before. The students Im
reaching with this style are the really motivat-
ed but poorly prepared students, she says.
And even her top students benefit. Like
other classes inspired by Beichners active-
learning approach, Colvins is arranged with
groups of students at tables. The top stu-
dents are leading and helping other students
through peer learning, she says. The stu-
dents like that role and say that it cements
their own understanding of the material.
Even physical chemistry is finding a
place in the realm of MOOCs and flipped
classrooms. This semester, Christopher J.
Cramer , a chemistry professor at the Uni-
versity of Minnesota, Twin Cities, is flipping
his computational chemistry class for the
first time. In May, he is scheduled to teach
a Coursera MOOC on thermodynamics .
He hopes to use the MOOC materials to flip Minnesotas ther-
modynamics class, which he last taught three years ago. As might
be expected for a course that recommends students already have
a year each of college chemistry and physics, the preregistration
after four weeks was only around 2,000 students, a relatively small
number for MOOCs.
Cramer plans to post his computational chemistry videos, which
are already publicly available on a Minnesota server, on YouTube
when the course ends in May, and he plans to do the same with the
videos from his Coursera MOOC. As more such videos become
available, flipped classes might be possible at institutions that lack
the resources to create such materials themselves. Instructors
might start treating the videos like they used to treat textbooks.
When a college instructor wants to teach a class, he or she hunts
around for the best textbook, Cramer says. You can imagine that
people will start hunting around to find the best video segments.
If it involves an entire MOOC, fabulous, but maybe well have little
sections that you hunt and click and buy (or get for free).
Cramer posits one reason that flipped classes help students
learn the material: Students willingly watch the videos, whereas
they resisted reading the textbook. Were tricking the students
into spending twice as much time on the material as they would
have otherwise, he says.
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44
BOOKS
A LOT OF PEOPLE are tired of Al Gore .
Hes a know-it-all. He can be preachy. Even
if he never claimed to have invented the
Internet, you can somehow imagine that he
might have made that claim.
Which is unfortu-
nate, because Gore
is a thoughtful, well-
informed commen-
tator on the current
state of the world. In
his ambitious new
book, The Future:
Six Drivers of Global
Change , Gore dem-
onstrates all of his
prodigious talents
and knowledge as
well as the traits that exasperate even his ad-
mirers. That said, The Future has far more
to recommend it than to detract from it.
The Future has been percolating in
Gores mind for eight years, he writes in the
introduction to the book, prompted by a
simple questionWhat are the drivers of
global change?someone asked him after
he had given a talk. The question became an
obsession, and two years ago, he concluded
that it would not leave me alone until I dug
in and tried to thoroughly answer it.
What emerged was this book, Gore
writes, a book about the six most impor-
tant drivers of global change, how they
are converging and interacting with one
another, where they are taking us, and
how we as human beingsand as a global
civilizationcan best affect the way these
changes unfold.
This leads to the straightforward struc-
ture of The Future, which consists of an
introduction, six long chapters devoted
to the six megatrends Gore perceives as
shaping humanitys future, and a relatively
brief conclusion that ties it all together.
The future isnt simple, needless to say, and
the six drivers Gore discusses in the book
have interesting historical origins, multiple
manifestations, and complex interactions
with each other, all of which makes for a
lively intellectual romp.
The following are the six drivers of
change Gore focuses on in this book:
The emergence of a deeply intercon-
nected global econ-
omy, which Gore
labels Earth Inc.
The emergence
of a worldwide elec-
tronic communica-
tions grid that links
billions of people to
each other and enor-
mous volumes of
data, a phenomenon
Gore labels The
Global Mind.
A significant shift in the balance of
power in the world from the West to the
East and a concurrent shift in power in the
U.S. from the public to corporations and
economic elites.
Rapid, unsustainable growth in popula-
tion, cities, resource consumption, pollu-
tion, and economic output.
Powerful new technologies that are fun-
damentally changing humanitys ability to
manipulate matter and life itself.
A radically new relationship between
humans and Earths ecological systems,
in particular humans impact on Earths
climate.
Gore digs into each of these topics with
gusto. He is an indefatigable researcher, and
his latest work brims with facts, factoids,
quotes, and expert opinion to support his
thesis that these six drivers of change are,
in fact, the most important forces shaping
our future. In some cases, one is tempted
to respond to Gores enthusiasm for a
technology or concern over a trend with an
exasperated, Oh, give me a break!
However, in the week that I was reading
The Future, a number of the technolo-
gies and trends Gore highlights in the book
turned up on the front pages of the Wash-
ington Post and the New York Times. For
example, Gore goes on at some length in
chapter one about the potential of three-
dimensional printing and concludes with
the factoid, Some advocates of more wide-
spread gun ownership are promoting the
3D printing of guns as a way to circumvent
regulations on gun sales. Really? I thought
to myself. On the front page of the next
days Washington Post was an article enti-
tled Parts made by 3D printers may stymie
gun-control efforts . Gore is very much on
top of technology trends.
GORE RANGES WIDELY in The Future,
delving into history, economics, sociology,
and broad swaths of science and technology
to advance his argument that there is no
prior period of change that remotely resem-
bles what humanity is about to experience.
Nor have we ever experienced so many
revolutionary changes unfolding simulta-
neously and converging with one another.
Gore is adept at pulling diverse threads
of information together to make a point
and often surprises the reader with an apt
and compelling quotation. In discussing
the Internet, for example, he observes that
many people use it as an extension of our
brains. This is not a metaphor; the stud-
ies indicate that is a literal reallocation of
mental energy. To illustrate the fact that
technology has long influenced the way
humans think, Gore turns to an ancient
source. He writes: In Platos dialogues,
when the Egyptian god Theuth tells one
of the kings of Egypt, Thamus, that the
new communications technology of the
agewritingwould allow people to re-
member much more than previously, the
king disagreed, saying, It will implant for-
getfulness in their souls; they will cease to
exercise memory because they rely on that
which is written, calling things to remem-
brance no longer from within themselves,
but by means of external marks.
Sometimes, however, the accumulation
AL GORES
CRYSTAL BALL
Former vice president maintains that six interacting
megatrends will determine HUMANITYS FATE on Earth
REVIEWED BY RUDY BAUM
There is no prior period of change
that remotely resembles what
humanity is about to experience.
THE FUTURE: Six
Drivers of Global
Change,
by Al Gore ,
Random House ,
2013 , 558 pages,
$30 hardcover
( ISBN: 978-0-
8129-9294-6 )
45
of data threatens to overwhelm the reader.
The chapter on the unsustainability of ex-
ponential growth begins promisingly. Gore
argues, convincingly I think, that the pri-
mary measure of economic growthgross
domestic productis based on absurd
calculations that completely exclude any
consideration of the distribution of in-
come, the relentless depletion of essential
resources, and the spewing of prodigious
quantities of harmful waste into atmo-
sphere, oceans, rivers, soil, and biosphere.
The chapter, though, ends up all over the
map, touching on resource depletion, pop-
ulation, immigration, refugees, groundwa-
ter and topsoil, phosphorus, dust storms,
oceans, and more. Yes, you are convinced
by the end of the chapter that humans are
out of control, but you also feel bludgeoned
with an unnecessary avalanche of data.
THE FUTURE HAS MUCH in it to in-
terest a wide range of readers. However,
conservatives of a certain stripe wont like
it at all. If you dont think humans are hav-
ing a significant impact on Earths climate,
youre not going to buy into Gores long
chapter on the subject that maintains that
humans are treating Earths atmosphere
as if it were an open sewer and that the
behavior of professional climate-change de-
niers borders on the criminal. And if you be-
lieve that Democrats are as responsible as
Republicans for the paralysis and dysfunc-
tion of government today, you are not going
to be open to Gores insistence that the
extreme conservative ideology that domi-
nates the Republican Party exists to thwart
reform and maintain the status quo for the
benefit of corporations and the wealthy.
One of the sections I found most intrigu-
ing was Gores examination of the history
of corporate influence in U.S. politics. He
harks back to the 1886 Supreme Court
decision that, in a backhanded sort of way,
granted corporations personhood. He
briefly discusses the Progressive move-
ment of the early-20th century and then
focuses on a deeply paranoid 1971 memo
from Lewis Powell (soon to be a member of
the Supreme Court) to the U.S. Chamber of
Commerce that argued that capitalism was
under assault and presented a compre-
hensive plan for a sustained and massively
funded long-term effort to change the na-
ture of the U.S. Congress, state legislatures,
and the judiciary in order to tilt the balance
in favor of corporate interests. Powell
wrote decisions while on the Court that
created the concept of corporate speech,
Gore notes, observing, While it is true
that corporations are made up of individu-
als, the absurdity of the legal theory that
corporations are personsas defined in
the Constitutionis evident from a com-
parison between the essential nature and
motives of corporations compared to those
of flesh-and-blood human beings.
Gore is a competent writer, and most
of The Future is a pleasure to read. The
book would have benefited from judicious
trimming in places where Gores enthusi-
asm for his subject overwhelms the reader.
And here and there throughout The Fu-
ture are sentences that leave you saying,
Huh? For example: Indeed, the new field
known as computational science has now
been recognized as a third basic form of
knowledge creationalongside inductive
reasoning and deductive reasoningand
combines elements of the first two by sim-
ulating an artificial reality that functions as
a much more concrete form of hypothesis
and allows detailed experimentation to
examine the new materials properties and
analyze how they can interact with other
molecules and materials.
CRITICS WILL ARGUE that Gore is es-
pousing socialism in many of his pre-
scriptions for a brighter future, but thats
hardly the case. He is calling for the re-
form of capitalism, not its abandonment.
The priority for those who agree that it is
crucial to restore the usefulness of capital-
ism as a tool for reclaiming control of our
destiny should be to insist upon full, com-
plete, and accurate measurements of val-
ue, he writes. So-called externalities that
are currently ignored in standard business
accounting must be fully integrated into
market calculations. In fact, externalities
such as our current neglect of the cost of
the pollution associated with burning fossil
fuels distort capitalism and lead to inap-
propriate and inefficient use of resources.
Gore maintains throughout The Fu-
ture that he is at heart an optimist and
that many of the dire trends he catalogs so
thoroughly can be mitigated and managed
successfully. In many ways, however, the
future Gore limns is bleak and the political
paralysis he decries unlikely to change any-
time soon. Nevertheless, he writes in the
books conclusion, The outcome of the
struggle to shape humanitys future that is
now beginning will be determined by a con-
test between the Global Mind and Earth
Inc. In a million theaters of battle, the
reform of rules and incentives in markets,
political systems, institutions, and societ-
ies will proceed or fail depending upon how
quickly individuals and groups commit-
ted to a sustainable future gain sufficient
strength, skill, and resolve by connecting
with one another to express and achieve
their hopes and dreams for a better world.
I hope Gore is right. Im not sure he con-
vinced me, however.
S
T
O
C
K
L
I
G
H
T
/
S
H
U
T
T
E
R
S
T
O
C
K
.
C
O
M
RUDY BAUM is C&EN editor-at-large.
INTELLECTUALLY ADEPT
Former vice president Al
Gore sounds warning bells
but maintains his optimism.
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ACS COMMENT
ANDY JORGENSEN , CHAIR , SOCIETY COMMITTEE ON EDUCATION
ACS Guidelines For Teaching
High School Chemistry
FOSTERING THE DEVELOPMENT of the
most innovative, relevant, and effective
chemistry education in the world is an
important goal in the American Chemical
Societys Strategic Plan for
2013 & Beyond . The Society
Committee on Education
(SOCED) is charged with
strengthening the science
education infrastructure
at all educational levels to
meet the changing needs
of the science community.
SOCED fulfills its charge in
part by developing and dis-
seminating outward-facing
reports, recommendations,
and policy.
In the spring of 2012,
SOCED released ACS
Guidelines and Recommen-
dations for the Teaching of
High School Chemistry, a
publication it had last re-
vised in 1984. The document
provides guidance on teach-
ing high school chemistry to
all students. It recognizes
the professional integrity
of chemistry educators who
are devoted to sharing and
upholding best teaching
practices and providing optimal facilities
to achieve excellence.
The goals of the revision are to reflect
changes in pedagogy, assessment, and
technology; offer recommendations for
improving the environment for teaching
and learning by all students; and gain broad
acceptance within the high school chemis-
try teaching community. Throughout the
writing process, the SOCED-appointed
team sought and incorporated feedback
from a variety of constituencies: high
school teachers and administrators; faculty
at two- and four-year postsecondary insti-
tutions; and select ACS committees, task
forces, and working groups.
Divided into three segments, the docu-
ment addresses areas critical for consider-
ation in any high school chemistry program.
The Pathways to Learning section
provides guidance on expected student out-
comes, the big ideas that should be explored
in a high school chemistry course, and ef-
fective student-centered
strategies for optimal
engagement and learning.
Recognizing that one size
does not fit all, this segment
also provides recommenda-
tions for teaching students
of diverse backgrounds and
various levels of academic
ability. It explores other top-
ics including assessment,
the role of technology, and
the laboratory experience.
The Physical Plant
section of the guidelines
includes recommenda-
tions for creating a safe and
dynamic learning environ-
ment that is student-cen-
tered and curriculum-driv-
en. The segment explores
classroom features, such
as the laboratory, teacher
work spaces, and chemical
storage facilities. Impor-
tant considerations include
safety equipment, labora-
tory equipment, room ar-
rangement, and technology. This section
of the document strongly recommends the
development of a comprehensive and re-
sponsible chemical management program
by teachers and administrators together.
Finally, the document speaks to the
Professional Preparations and Responsi-
bilities of high school chemistry teachers.
It identifies strategies enabling teachers to
create teaching and learning environments
that promote equal opportunities for all
students to learn chemistry. This segment
discusses the ethical considerations, such
as ensuring a safe and productive class-
room along with an unbiased presentation
of content, that exist at the intersection
of science and teaching. Recognizing that
teaching is a complex and intellectually
challenging profession, this section also
addresses the importance and character-
istics of effective professional develop-
ment. And it lists examples of professional
organizations and resources that support
professional development.
THE GUIDELINES have been disseminated
broadly through distribution channels
including networks of high school chem-
istry teachers; Listservs; and numerous
local, state, and national conferences. Ad-
ditionally, members and staff of ACS have
directly contacted more than 6,000 school
district science supervisors across the U.S.
with information about this important
document. Symposia and presentations
have been held at conferences including
the fall 2012 ACS national meeting in Phila-
delphia; the 2012 Biennial Conference on
Chemical Education at Pennsylvania State
University; and the 2012 National Science
Teachers Association Area Conferences in
Atlanta, Louisville, and Phoenix. These fa-
cilitated sessions have provided the oppor-
tunity to raise awareness of the guidelines
and collect important feedback that will
inform supplements and future revisions
of the document. Additional symposia and
presentations are slated for 2013.
Members of the high school teaching
community have provided positive feed-
back on the guidelines. Many have empha-
sized the importance of the document in
advocating for the continuation and sup-
port of chemistry programs at their institu-
tions. Others have noted the usefulness of
the guidelines in informing administrators
about best practices in chemistry instruc-
tion, particularly as they pertain to the
laboratory setting.
We hope that the entire ACS member-
ship will join us in broadly disseminating
the guidelines to high school chemistry
teachers in their communities. You can
visit www.acs.org/hsguidelines to view
the full report and download a PDF of the
document. Please send e-mail requests for
hard copies to education@acs.org.
Views expressed on this page are those of
the author and not necessarily those of ACS.
We hope that
the entire ACS
membership will
join us in broadly
disseminating the
guidelines to high
school chemistry
teachers in their
communities.
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48
IF YOURE A FAN of the idea of promoting
science through art, you may be intrigued
by a burgeoning program set up by the
American Chemical Societys Southern
Nevada Section .
When brainstorming imaginative ways
to celebrate the International Year of
Chemistry in 2011, the section decided to
sponsor a chemistry-themed poster con-
test for area high school students. Not only
was the competition successful from the
get-go, but it has now morphed into an an-
nual event that continues to influence the
local community.
Currently gearing up for its third year,
the contest has inspired talented young
artists to produce posters that vividly il-
lustrate concepts such as basic chemical
principles and chemistrys broad applica-
tion in fields as diverse as pharmaceuticals
and alternative energy.
Most important, it has
served as an effective
outreach tool, drawing
interest from students
who might not otherwise
ponder the power and
benefits of chemistry,
observes Roger Rennels, the sections pub-
lic relations chair, who came up with the
contest idea.
As the section set out to launch the
contest in 2011, it drew heavily on the
resources of the local public school
district. The Clark County School Dis-
tricts School-Community Partnership
Program and its assistant director, Judy
SHOWCASING
CHEMISTRY
Through its annual POSTER CONTEST, the ACS Southern Nevada
Section inspires students to explore the power of chemistry
SUSAN J. AINSWORTH , C&EN DALLAS
FIRST PLACE
Christy Adaya,
grade 12,
Shadow Ridge
High School,
Las Vegas.
ACS NEWS
49
THIRD PLACE Rileigh
Sorensen, grade 12,
Foothill High School,
Henderson, Nev.
Myers, provided critical guidance
and help implementing the project.
For example, Myers encouraged the
section to limit the contest to high
school students to control costs, and
she provided information about suc-
cessful contests held in the district
in the past, which helped the section
structure its poster contest and de-
fine its rules.
More specifically, Myers advised
the section to offer cash prizes, for
students as well as for the teachers
who sponsor the winning posters, as a
way to maximize the number of con-
test entrants, Rennels says. More than
200 students participated in 2012.
The first-place
student winners
received $500,
and second- and
third-place
finishers got
$250 and $100, respectively. In addition,
each sponsoring teacher won half of the
amount that his or her student received.
In addition, in 2012, the top eight stu-
dent runners-up each
received a $25 gift card,
which were donated by
VWR International, a
laboratory supply and
distribution company.
Rennels, along with
fellow Southern Ne-
vada Section executive
committee members
Onofrio (Dick) Gaglione
and Kazumasa (Kaz)
Lindley, served as judges
for the contest.
To further enhance
its outreach power
during the most recent
awards ceremony, the
section invited under-
graduate and graduate
students to present re-
search posters that they
had entered in another
contest the section
sponsors, Rennels says.
Through this effort, he
explains, we wanted
to share the high school
students posters with
the greater chemical
community in southern
Nevada, and we wanted
the high school students
to see how the college
students posters are
used to convey scientific
knowledge.
Rennels believes
that the high school
poster contest has
been effective in
sparking curiosity about chemistry among
students. Recently, an art teacher told
him that many of her students who were
participating in the contest frequently
would go across the hall to talk with
the chemistry teacher about chem-
istry. And that, Rennels says, is
something many of these students
would never have done if not for
this contest.
SECOND PLACE Ashley
Armenta, grade 9,
Southeast Career
Technical Academy,
Las Vegas.
See more of the dynamic, chemistry-focused posters that
garnered contest honors at http://cenm.ag/poster.
MORE ONLINE
RUNNER-UP Deborah
Diaz, grade 9,
Southeast Career
Technical Academy,
Las Vegas.
RUNNER-UP
Yoseph Hobe,
grade 10, Rancho
High School,
Las Vegas.
50
ACS NEWS
WHEN THE American Chemical Society
Council meets next month in New Orleans,
it will select candidates for national office
and vote on a change to society dues and on
petitions relating to an ACS international
chapter and the presidential election pro-
cess. Councilors will also brainstorm ways
the society can help members succeed in
the global chemical enterprise.
The Committee on Nominations & Elec-
tions (N&E) laid the groundwork for the
council last fall, when it prepared a slate of
nominees for the office of ACS president-
elect for 2014. The four nominees are G.
Bryan Balazs, associate program leader,
Lawrence Livermore National Laboratory,
California; Charles E. Kolb Jr., president
and chief executive officer, Aerodyne
Research, Billerica, Mass.; Carolyn Ribes,
business analytical leader at Dow Chemi-
cal, Terneuzen, the Netherlands; and Diane
Grob Schmidt, R&D section head at Proc-
ter & Gamble, Cincinnati.
A President-Elect Nominee Town Hall
Meeting will be held in Hilton Exhibition
Center A at the Hilton New Orleans Riv-
erside Hotel on Sunday, April 7, 4:455:45
PM. Nominees, councilors, and other ACS
members can interact at this event via a
moderated question-and-answer format.
During the council meeting on the follow-
ing Wednesday, councilors will select two
of the nominees to run this fall as official
candidates for 2014 president-elect.
Last fall, N&E also prepared slates of
nominees for the position of director in
Districts II and IV for the 201416 term.
Earlier this month, councilors in the two
districts chose candidates from among
those nominees. The selected candidates,
who will be named during the council
meeting in New Orleans, will stand for
election in the fall.
Nominees who agreed to run for Dis-
trict II director are George M. Bodner,
Arthur E. Kelly Distinguished Professor of
Chemistry, Education & Engineering, Pur-
due University; Jed F. Fisher, professional
specialist on the faculty of the departments
of chemistry and biochemistry, University
of Notre Dame; Alan A. Hazari, director of
chemistry labs and lecturer, University of
Tennessee, Knoxville; and Robert A. Pri-
bush, professor of chemistry, Butler Uni-
versity, Indianapolis.
Nominees who agreed to run for direc-
tor of District IV are John P. Fackler Jr., dis-
tinguished professor emeritus of chemistry
and toxicology, Texas A&M University,
College Station; Rigoberto Hernandez,
professor in the School of Chemistry &
Biochemistry at Georgia Institute of Tech-
nology, Atlanta; Larry K. Krannich, pro-
fessor emeritus of chemistry, University
of Alabama, Birmingham, and executive
director, Alabama Academy of Science,
Birmingham; and John A. Whittle, retired
director of risk management, Lamar Uni-
versity, Beaumont, Texas.
CANDIDATES WHO AGREED to run for
director-at-large, a group from which
councilors will elect two directors this fall
for the 201416 term, are Susan B. Butts,
independent consultant, Susan B. Butts
Consulting, Midland, Mich.; Thom H.
Dunning Jr., director of the National Cen-
ter for Supercomputing Applications and
of the Institute for Advanced Computing
Applications & Technology, and Distin-
guished Chair for Research Excellence in
Chemistry, University of Illinois, Urbana-
Champaign; Dorothy J. Phillips, director
of strategic marketing, Waters Corp.,
Milford, Mass.; and Kathleen M. Schulz,
president of Business Results, Albuquer-
que, N.M.
The council will vote on an alternative
version of the Petition to Amend Na-
tional Election Procedures, which would
amend the societys bylaws to change the
election process for ACS president-elect.
The original version of the petition came
up for consideration at the fall 2012 na-
tional meeting. The alternative version
clarifies wording of the petition, which is
intended to shorten the campaign period
for candidates for ACS president-elect.
It would also charge the Committee on
Nominations & Elections with propos-
ing two candidates for president-elect,
rather than having the council vote on
a list of four nominees, as it currently
does. The process remains unchanged for
candidates to be nominated by petition.
Councilors will also vote on the Peti-
tion to Charter One New International
Chemical Sciences Chapter, which would
allow for the establishment of an ACS
chapter in Romania.
In addition, the Committee on Constitu-
tion & Bylaws (C&B), in cooperation with
the Committee on International Activities,
is asking council to approve changes to
the charter bylaws for new international
chemical sciences chapters. These changes
would require C&B to review proposed by-
law changes before changes are approved
by a chapters membership.
A two-thirds vote of the council and
subsequent confirmation by the ACS Board
of Directors are required to amend the so-
cietys bylaws.
The full text of petitions and associated
committee reports are available at www.
acs.org/bulletin5 (click on Petitions).
The council will engage in a special
discussion of the question: What else
should ACS do to help members to thrive
in the global chemistry enterprise? This
discussion relates to a task force recently
commissioned by ACS President Marinda
Li Wu entitled Vision 2025: Helping ACS
Members Thrive in the Global Chemistry
Enterprise, which aims to identify oppor-
tunities with respect to jobs, advocacy, and
strategic collaboration.
The Committee on Economic & Profes-
sional Affairs will ask the council to ap-
prove a minor revision of the Academic
Professional Guidelines, which were last
updated in 2008. A more extensive revision
is under way and will be presented to the
council for consideration in 2014.
The Committee on Local Section Activi-
ties will ask the council to approve a change
in the way that ACS distributes funds to
local sections, beginning in 2014. The exist-
ing formula is expressed in dollar amounts
that are adjusted upward each year. If that
formula were to remain in place, the total
allotment for local sections would soon ex-
ceed the money available to distribute. The
proposed formula instead uses percentages
to allocate funds.
Other business before the council in-
cludes approval of a $3.00 increase in ACS
dues to $154 for 2014.
The ACS Council meeting will be held
on Wednesday, April 10, in Grand Ballroom
AC of the Hilton New Orleans Riverside
Hotel. All ACS members are encouraged to
attend the meeting, which starts at 8 AM.
SUSAN AINSWORTH
COUNCIL PREVIEW
Candidate selections and petitions are on the agenda for
the spring ACS NATIONAL MEETING in New Orleans
51
AWARDS
LINDA WANG compiles this section.
Announcements of awards may be sent to
l_wang@acs.org.
AWARDS
STONE AWARD TO
DAN REGER
Daniel L. Reger, Carolina Distinguished
Professor of Chemistry & Biochemistry at
the University of South Carolina, is the re-
cipient of the 2011 Charles H. Stone Award
sponsored by the ACS Charlotte/Piedmont
Section. The award is given every two years
to the most outstanding chemist in the
southeastern U.S. Reger received the award
during a meeting of
the section in October
2012.
Regers research is
in synthetic inorganic
chemistry. He has stud-
ied the properties of al-
kylmetal complexes, in-
cluding -elimination
and alkyl isomerization
reactions. He developed the chemistry of
poly(pyrazolyl)borate and poly(pyrazolyl)
methane ligands. These ligands have been
used to prepare and study spin crossover
complexes and dinuclear metallacycles that
show strong antiferromagnetic properties.
For more information on COMPs
awards, visit https://sites.google.com/a/
acscomp.org/site2011/awards .
CHEMICAL TECHNICIAN
AWARD TO SHANE KIRK
Shane Kirk, a technologist associate in the
chemical process engineering research lab
at Eastman Chemical, is the recipient of the
2013 National Chemical Technician Award,
which honors excel-
lence and professional-
ism among technicians,
operators, analysts, and
other applied chemical
technology profes-
sionals. The award is
administered by the
American Chemical
Society Committee on
Technician Affairs and sponsored by the for-
mer Division of Chemical Technicians.
Kirk is a contributor on 12 patents and
an author on nearly 200 internal technical
reports. The technical areas of his reports
include membrane feasibility experiments,
crystallization and filtration troubleshoot-
ing for a plant start-up, and crystalliza-
tion residence time studies for a capacity
increase.
Kirk will receive the award, which in-
cludes a $1,000 honorarium, during the
spring 2013 ACS national meeting in New
Orleans.
COMP DIVISION
2012 AWARDS
The ACS Division of Computers in Chem-
istry (COMP) presented several awards
during the fall 2012 ACS national meeting
in Philadelphia.
The OpenEye Outstanding Junior Fac-
ulty Award in Computational Chemistry
assists new faculty members in gaining
visibility within the COMP community.
The winners are Gregory Beran, University
of California, Riverside; Jerome Delhom-
melle, University of North Dakota; Michael
R. Shirts, University of Virginia; and Yaro-
slava G. Yingling, North Carolina State Uni-
versity. Each winner received a $1,000 prize.
The CCG Graduate Student Excellence
Award, cosponsored by the Chemical Com-
puting Group (CCG), recognizes outstand-
ing research performance by a graduate
student in computational chemistry. The
recipients are Sean Fischer, University
of Washington; Brian Gold, Florida State
University; Emilie Guidez, Kansas State
University; Nikolay Plotnikov, Univer-
sity of Southern California; and Yue Shi,
University of Texas, Austin. The winners
received $1,150 and a copy of CCGs MOE
(Molecular Operating Environment) soft-
ware with a one-year license.
The ACS Peter Kollman Graduate Award
in Supercomputing recognizes outstanding
students in the early stages of their graduate
careers, particularly for projects that need
high-performance computing resources for
chemistry-related projects. The recipients
are Brian Radak, Rutgers University, Pis-
cataway, and Mijo Simunovic, University
of Chicago. Each winner has been allocated
computing time on the Kraken Cray XT5
supercomputer at the National Institute for
Computational Sciences.
SCENE
materials
LATEST NEWS FROM C&EN
ABOUT MATERIALS, CATALYSIS, NANOTECH-
NOLOGY, AND INORGANIC CHEMISTRY
cen.acs.org/materials
SCIENCE TALENT SEARCH
NAMES WINNERS
Sara Volz, 17, of Colorado Springs, Colo.,
won the top prize of $100,000 in the 2013
Intel Science Talent Search for her re-
search on algal biofuels. Volz used artificial
selection to establish populations of algae
cells with high oil content, which is essen-
tial for an economically feasible source of
biofuel.
Jonah Kallenbach, 17, of Ambler, Pa.,
won the $75,000 second-place prize for
designing a computer program that pre-
dicts how disordered proteins interact
with ordered proteins in the body. The
work has the potential to yield a new para-
digm for drug design in which disordered
regions can be used as promising new drug
targets for diseases such as cancer and
tuberculosis.
The $50,000 third-place prize in the
Intel competition went to Adam Bowman,
17, of Brentwood, Tenn., for his design of
an inexpensive low-energy pulsed plasma
device. He says his work could open the
door for plasma research to be conducted
in small-scale operations, perhaps even in
high school laboratories.
The annual competition recognizes U.S.
high school seniors who are conducting
innovative research in science, technology,
mathematics, and engineering.
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ACADEMIC POSITIONS
THE KEKUL-INSTITUTE for Organic Chemistry and
Biochemistry at the University of Bonn (Germany) in-
vites applications for an Associate Professorship W2
of Organic Chemistry and a Tenure-Track Assistant
Professorship W1 of Organic Chemistry which may
be tenured on an Associate Professor level (W2). The
applicant should work successfully in a current field
of organic chemistry that complements the research
focus of the Kekul-Institute (e.g. study of biological
questions using organic chemistry or analytics of com-
plex systems). Disabled persons and women are par-
ticularly encouraged to apply. For more information,
visit http://www.chemie.uni-bonn.de/vacancies.
Applications (CV, credentials, up to three publica-
tions, teaching experience, third-party funding) should
be sent by mail until April 30, 2013, to the Chairman
of the Department of Chemistry, Gerhard-Domagk-
Str. 1, 53121 Bonn, Germany.
RESEARCH SPECIALIST
Physics: The ASU Femtosecond
Crystallography Initiative
ASU, in Tempe, AZ, seeks a Research Specialist to
fabricate nozzle assemblies and other components
for sample-delivery devices required by X-ray free-
electron lasers, to develop new fabrication methods,
and to produce CAD drawings (e.g. Solid Works) from
sketches for this and related instrumentation pro-
vided by the supervisor. Deadline: 11:59 pm, April 5,
2013. Applications will continue to be accepted and
reviewed every week thereafter until search is closed.
Salary: $32,037-$37,800. DOE. AA/EOE. For qualifi-
cations/application info, see Job ID # 30427 at www.
asu.edu/asujobs/.
ASSOCIATE FOR RESEARCH SUPPORT
Department of Chemistry and Biochemistry
University of Notre Dame, Notre Dame, IN
The successful candidate will operate with the broad
remit of advancing the research mission of the De-
partment. In this capacity, the incumbent will work
closely with faculty to: 1) provide technical input and
both written and graphic assistance for grant pro-
posals and scientific manuscripts; 2) explore private
and federal funding opportunities for researchers;
3) identify and establish ties with industrial partners;
4) organize and publicize on- and off-campus confer-
ences; and 5) assist in developing and maintaining
individual group web pages. The incumbent will also
assist in broadly publicizing the research enterprise
of both the Department and individual researchers
through modern modes of communication and so-
cial media (websites, blogs, videos, Facebook, Twit-
ter, etc.), design and provide content for brochures
and other related publicity items, prepare materials
for faculty award nominations, and serve as the De-
partments graduate alumni development contact
including maintaining and providing content and for
the Departments alumni newsletter. Ideally, the can-
didate will possess excellent technical and non-tech-
nical writing skills, good interpersonal communication
skills, general knowledge of terminology/techniques
in modern chemical and biochemical research, facility
with a variety of software applications, and familiarity
with social media. A Ph.D. (or equivalent) in a scien-
tific field is required. The salary range for the position
is $40,000$65,000. Please apply online at http://
ND.jobs to Job #13107 or visit http://jobs.nd.edu/
applicants/Central?quickFind=59989. The Univer-
sity of Notre Dame is an equal opportunity/affirmative
action employer.
THE UNIVERSITY OF SOUTHERN MISSISSIPPI
CHEMISTRY/BIOCHEMISTRY
The Department of Chemistry and Biochemistry
(www.usm.edu/chemistry-biochemistry) invites ap-
plications for a tenure-track assistant professor posi-
tion in organic chemistry beginning either August 2013
or January 2014. The University of Southern Missis-
sippi is a research-extensive university with approxi-
mately 17,000 students. The graduate program of the
Department of Chemistry and Biochemistry offers
Ph.D. and M.S. degrees. Candidates must have a Ph.D.
degree in chemistry or a closely related area and at
least two years of postdoctoral research experience.
The successful applicant is expected to develop a vig-
orous, externally funded research program and must
be committed to excellence in teaching and service.
Applications for this position must be submitted on-
line at https://jobs.usm.edu. Review of applications
will begin May 1, 2013, and will continue until the posi-
tion is filled. AA/EOA/ADAI.
52
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G
The University of Bremen together with the Alfred-Wegener-Institute, Helmholtz
Centre for Polar and Marine Research, invites applications for a bridge
professorship in Marine Chemistry (W2/W3), focusing on chemical processes in
marine systems
The University of Bremen supports a broad range of academic disciplines. The quality
of its research strategy is reected in its status as one of eleven universities that were
recognized within the German Excellence Initiative. Bridge professorships will now
further strengthen the high-prole research areas of the university by expanding
existing relationships between the university and the non-university research partners
and creating additional innovative elds of research.
In this framework, the University of Bremen (Faculty 2 Biology/Chemistry), together
with the Alfred-Wegener-Insti-tute, Helmholtz Centre for Polar and Marine Research,
is offering conditional to the release of budgetary funds the position of a
Professor
Salary group W2/W3 - Associate or Full Professor level,
depending on qualications, on a permanent position for
Marine Chemistry
reference number: P 925 / 13
The professorship will be focusing on chemical processes in marine systems. It will
be situated within an interdisciplinary network of excellence in marine sciences,
encompassing the University of Bremen with its faculties in Biology/Chemistry and
Geosciences and the MARUM Center for Marine Environmental Sciences together
with the Alfred-Wegener-Institute, Helmholtz Centre for Polar and Marine Research,
the Max Planck Institute of Marine Microbiology, the Leibniz-Center for Tropical
Marine Ecology, and the Institute for Chemistry and Biology of the Marine Environ-
ment (ICBM) at the Carl von Ossietzky University Oldenburg. This network offers
outstanding opportunities for access to state-of-the-art infrastructures of analytical
instrumentation, research vessels and underwater technology; within this excellent
setting the successful candidate will provide innovative research impulses and initiate
new projects in marine chemistry or chemical oceanography that will lead to a
profound understanding of the interactions between (geo-)chemical and biological
processes in marine environments. The position is one of six interdisciplinary bridge
professorships within the framework of the Excellence Initiative at the University of
Bremen. The professorship is associated with the Faculty 2 (Biology/Chemistry) and
will focus on key research questions in the marine sciences that will be addressed
employing cutting-edge techniques.
Candidates should be renowned for their scientic expertise in marine chemistry or
chemical oceanography, excellence in research, and demonstrated research
leadership. Successful experience in interdisciplinary projects with biologists and/or
geoscientists is required. Demonstrated success and strong potential in the
acquisition of externally funded projects is important.
Prerequisites for an appointment are a pertinent doctoral degree, an outstanding
record of scientic achievements, and international visibility. Successful applicants
are expected to teach marine chemistry and general chemistry courses at the
Bachelor and Master level. Applicants must be able to teach in English and are
expected to have acquired teaching skills in German within 2 to 3 years.
We expect willingness to cooperate with other research areas within and outside the
University of Bremen, and acquise third-party funds as well as openness to innovations
in teaching methods. Experience with media-supported forms of teaching is desirable.
The University of Bremen has received a number of awards for its diversity policies
and offers a family-friendly working environment. We strive to increase the number of
female researchers and particularly solicit applications from qualied female
candidates. International applications are explicitly welcome. Persons with disabilities
will, with appropriate qualications and aptitudes, be employed preferentially.
Informal inquiries to the position can be directed to the dean of the Faculty 2 (Biology/
Chemistry), Prof. Dr. Thomas S. Hoffmeister, e-mail: dekanfb2@uni-bremen.de
Applications, including a curriculum vitae, qualifying documentation (publications,
evidence of external funding, teaching experience) and a short research and teaching
plan (maximum of 4 pages for both) should be submitted preferentially by e-mail in
a single PDF le to the address below. Closing date is April 15, 2013.
The postal address for all applications is
University of Bremen
Faculty 2 (Biology/Chemistry)
the Deans Ofce
Leobener Str. NW2
28359 Bremen Germany
e-mail: dekanfb2@uni-bremen.de
Homepage: http://www.uni-bremen.de/
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56
newscripts
SIGN UP FOR THE
ENVIRONMENTAL
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LATEST NEWS FROM C&EN
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cen.acs.org/environment
W
ith just 10 or so miles separating
England from France, there are
days when a Brit can catch sight
of the French coastline and almost smell the
hot croissants and pain au chocolat. In late
January, however, the smell emanating from
northern France was anything but appetizing.
A sulfurous ROTTEN-EGG SMELL rst
tingled the senses of inhabitants across
northern France on Jan. 21. The source of
the smell was Lubrizol , a specialty chemi-
cal manufacturer with a production plant in
Rouen, 75 miles northwest of Paris. The prob-
lem was an uncontrolled release of mercap-
tan, a nontoxic organosulfur
compound that companies
add to natural gas to give it a
detectable smell.
Mercaptans, also known
as thiols, are detectable by
the human nose at concen-
trations of about 10 ppb.
Anyone who has smelled
skunk spray, made of low-
molecular-weight mercap-
tans and derivatives, will
have an inkling of Frances
problem.
By the evening after the
release, the stench had
blown southward into the
fringes of Paris northern
suburbs. The olfactory
ofensive was so awful that
people were forced to stay
indoors, with many reporting nausea and
headaches.
Mercaptan was still leaking from the
plant the next day, when the wind switched
to blow in a southeasterly direction. Unsus-
pecting Brits in southeastern England got a
whif just in time for breakfast.
Before long, the stench was picked up by
the British media. Does your street have a
strange pong? BBCs Jeremy Vine asked
millions of listeners during his midday radio
phone-in show. Apparently it smells of
sweat, garlic, and rotten eggs, said Jimmy
Carr, a comedian and the host of TV quiz
show 8 out of 10 Cats . According to the
acerbic Carr, The cause has been narrowed
down to two sources: everything in France,
or everyone in France.
W
ithin days it was Englands turn
to be the source of an unpleasant
smell, albeit a more localized one:
This time the pong was from a 3-kg lump
of ambergris, the INTESTINAL SLURRY of
THE FRENCH STENCH, THE ENGLI SH PONG, THE CHEESY NORWEGI ANS
M
A
N
C
H
E
S
T
E
R

E
V
E
N
I
N
G

N
E
W
S
S
H
U
T
T
E
R
S
T
O
C
K
a sperm whale
that has hardened
over time into a
waxy material. The
stuf had washed
up onto Morecambe
beach, in northwest
England. Local man
Ken Wilman discov-
ered the football-sized lump while walking
his dog. It smelled horrible, Wilman told
Mirror News.
Ambergris is said to have a musky smell
that improves as the material oxidizes.
So the heavily scented
substance is used as
a base for a number of
perfumes. But because
there are no commercially
available alternatives, its
highly sought after by the
perfume industry.
A French ambergris
dealer has reportedly
ofered Wilman $65,000
for his smelly lump. And
Wilman might want to ex-
pedite the sale: In October,
researchers at Firmenich , a
Geneva-based avors and
fragrances rm, published
a scientic paper outlining
a cost-efective bioprocess
for generating sclareol, a
diterpene analog that can
substitute for ambergris scentwise ( J. Am.
Chem. Soc., DOI: 10.1021/ja307404u ).
A
s smelly as they were, the ambergris
and mercaptan episodes might have
been out-odored by a concur-
rent event in Norway: As mercaptan wafted
across France and England, about 27 tons of
caramelized BROWN GOAT CHEESE, a na-
tional delicacy named brunost, was burning
uncontrollably in northern Norways Brattli
road tunnel. Fueled by the cheeses high fat
and sugar content, the cheesy re spewed
noxious fumes from a mile inside the tunnel
for ve days before it could be extinguished.
Local police told news outlets the cheese
burned almost like petrol.
Europes year has certainly begun with
a stink.
High-priced smell: Wilman
has been offered $65,000
for the ambergris he and
his dog, Madge, found.
Brunost: A highly
flammable goat
cheese.
ALEX SCOTT wrote this weeks column.
Please send comments and suggestions to
newscripts@acs.org.
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As Asia's leading pharma industry and the world's second largest mark
ntry to nd the latest technologies and innovative products. Building partnerships and
understanding the market are crucial key success factors to enter this $60 billion mark
As Asia's leading pharma industry and the world's second largest market, Japan is th
country to nd the latest technologies and innovative products. Building partn
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Register now at
www.cphijapan.com
The ideal networking platform for Japans
pharma market
Your direct route into Asias largest pharma market
Japanese pharma is at a turning point.
Its already the worlds second-largest pharma
market. But now a powerful mix of domestic growth,
increasing globalization and favourable legislation is
opening up a huge range of new opportunities.
If you want to be part of the success story, you cant
afford to miss CPhI in 2013.
CPhI Japan - brings together more than 450 exhibitors from over
29 countries. A total of 14,000 executives and decision makers
from all over the globe come together for three days of lead
generation, networking and industry research.
Theres even more value from four co-located shows (P-MEC for
machinery, ICSE for services, BioPh for biopharma and Pharmatec
for packaging), plus dozens of seminars and conferences covering
key industry topics.
Register online today for free entrance at www.cphijapan.com

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