How to build a better test for chemical toxicity P.16
Athletes at Rio Olympics face stricter doping tests P.25
AUGUST 8, 2016
Synchrotron science High-energy facilities across the globe are helping researchers reveal the inner secrets of materials P.28
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Contents VOLUME 94, NUMBER 32
August 8, 2016
Features Cover story
25 Athletes at Rio Olympics face sophisticated doping tests
Revealing materials’ secrets with synchrotron light
Ofcials can now check for longago anabolic steroid use, with gene doping tests on the horizon.
16 Making sure chemical toxicity tests don’t miss metabolites EPA looks to incorporate metabolism into highthroughput chemical screening.
These powerful light sources, able to probe a wide range of materials, attract a diverse array of researchers. Page 28
21 Measuring a serial entrepreneur’s success By any yardstick, Robert Langer’s creation of 31 start-ups is a testament to his technical and business acumen.
24 How rare earths bring clean technologies, dirty landscapes Unsustainably mined rare earths from China play major role in wind turbines and hybrid cars.
27 Periodic Graphics Compound Interest blogger Andy Brunning explains the chemistry behind the Russian doping scandal.
Quote of the week
On the cover Aerial view of the National Synchrotron Radiation Research Center in Taiwan. Photograph from the National Synchrotron Radiation Research Center
“As scientists with a natural tendency to collaborate, we owe it to our society to try to build a bridge to understanding.”
Departments
2 Editor’s Page 3 Reactions —Eliezer Rabinovici, physics 5 Concentrates professor, Hebrew University of 37 C&ENjobs Jerusalem Page 28 40 Newscripts CENEAR 94 (32) 1–40 • ISSN 0009-2347
ACS News 34 ACS Comment 35 Awards
From the Editor 1155—16th St., N.W., Washington, DC 20036 (202) 872-4600 or (800) 227-5558 EDITOR-IN-CHIEF: Bibiana Campos Seijo MANAGING EDITOR, EDITORIAL: Amanda Yarnell MANAGING EDITOR, PRODUCTION: Rachel Sheremeta Pepling BUSINESS DEVELOPMENT & PUBLISHER: Kevin A. Davies SENIOR ADMINISTRATIVE OFFICER: Marvel A. Wills BUSINESS NEW YORK CITY: (212) 608-6306 Michael McCoy, Assistant Managing Editor, Rick Mullin (Senior Editor), Marc S. Reisch (Senior Correspondent), Alexander H. Tullo (Senior Correspondent), Rachel Eskenazi (Administrative Assistant). CHICAGO: (917) 710-0924 Lisa M. Jarvis (Senior Correspondent). HONG KONG: 852 9093 8445 Jean-François Tremblay (Senior Correspondent). HOUSTON: (281) 486-3900 Ann M. Thayer (Senior Correspondent). LONDON: 44 1494 564 316 Alex Scott (Senior Editor). WEST COAST: (315) 825-8566 Melody M. Bomgardner (Senior Editor) POLICY Cheryl Hogue, Assistant Managing Editor Britt E. Erickson (Senior Editor), Jessica Morrison (Associate Editor), Andrea L. Widener (Senior Editor) SCIENCE/TECHNOLOGY/EDUCATION WASHINGTON: Lauren K. Wolf, Assistant Managing Editor Celia Henry Arnaud (Senior Editor), Stuart A. Borman (Senior Correspondent), Matt Davenport (Associate Editor), Stephen K. Ritter (Senior Correspondent). BERLIN: 49 30 2123 3740 Sarah Everts (Senior Editor). BOSTON: (973) 922-0175 Bethany Halford (Senior Editor). CHICAGO: (847) 679-1156 Mitch Jacoby (Senior Correspondent). WEST COAST: (626) 765-6767 Michael Torrice (Deputy Assistant Managing Editor), (925) 226-8202 Jyllian Kemsley (Senior Editor), (510) 390-6180 Elizabeth K. Wilson (Senior Editor) JOURNAL NEWS & COMMUNITY: (510) 768-7657 Corinna Wu (Senior Editor) (651) 447-6226 Jessica H. Marshall (Associate Editor) ACS NEWS & SPECIAL FEATURES Linda Wang (Senior Editor) EDITING & PRODUCTION Kimberly R. Bryson, Assistant Managing Editor Craig Bettenhausen (Associate Editor), Taylor C. Hood (Contributing Editor), Jeff A. Huber (Associate Editor), Lillian Steenblik Hwang (Contributing Editor), Manny I. Fox Morone (Associate Editor), Alexandra A. Taylor (Contributing Editor) CREATIVE Robert Bryson, Creative Director Tchad K. Blair, Interactive Creative Director Robin L. Braverman (Senior Art Director), Ty A. Finocchiaro (Senior Web Associate), Yang H. Ku (Art Director), William A. Ludwig (Associate Designer) DIGITAL PRODUCTION Renee L. Zerby, Manager, Digital Production Luis A. Carrillo (Web Production Manager), Marielyn Cobero (Digital Production Associate), Joe Davis (Lead Digital Production Associate), Krystal King (Lead Digital Production Associate), Shelly E. Savage (Senior Digital Production Associate), Cesar Sosa (Digital Production Associate) PRODUCTS MANAGER: Pamela Rigden Snead CONTENT MARKETING EDITOR: Mitch A. Garcia SALES & MARKETING Stephanie Holland, Manager, Advertising Sales & Marketing Natalia Bokhari (Digital Advertising Operations Manager), Kirsten Dobson (Advertising and Marketing Associate), Sondra Hadden (Senior Digital Marketing Specialist) ADVISORY BOARD Deborah Blum, Raychelle Burks, Kendrew H. Colton, François-Xavier Coudert, Cathleen Crudden, Paula T. Hammond, Matthew Hartings, Christopher Hill, Peter Nagler, Dan Shine, Michael Sofia, Michael Tarselli, William Tolman, James C. Tung, Jill Venton, Helma Wennemers, Geofrey K. Wyatt Published by the AMERICAN CHEMICAL SOCIETY Thomas M. Connelly Jr., Executive Director & CEO Brian D. Crawford, President, Publications Division EDITORIAL BOARD: Nicole S. Sampson (Chair), ACS Board of Directors Chair: Pat N. Confalone, ACS President: Donna J. Nelson, Cynthia J. Burrows, Michael P. Doyle, Jerzy Klosin, Gary B. Schuster Copyright 2016, American Chemical Society Canadian GST Reg. No. R127571347 Volume 94, Number 32
The Olympics are here
T
he Olympics are finally here. The opening ceremony kicked things off last Friday, and you can expect to hear or see coverage about the games until at least their last day on Aug. 21. I have always watched the games on TV and thoroughly enjoyed them. Growing up, I remember watching Carl Lewis—who won 10 Olympic medals in his career— breaking the 100-meter record. More recently, I have enjoyed swimmer Michael Phelps beating all records in the pool and arguably becoming the best Olympian of all time with a total of 22 medals. By the way, if the mention of Phelps and swimming pools makes you wonder, does he pee in it? The answer is yes, and I recommend you visit cenm.ag/pool, not only to watch a video of him admitting it, but also to read our special report on the chemical reactions between disinfectants and organic matter—sweat, urine, and personal care products—that take place in swimming pools everywhere. In any case, I don’t remember the buildup to the Olympic Games ever being a smooth process. Chaos and rumors often dominate headlines leading up to the games: Will the stadium be ready on time? How much over budget have the organizers gone? But the buildup to the 2016 Games in Brazil has been the most turbulent I can remember. In fact, Rio is regarded as one of the least-prepared host cities in Olympic history. The country is in the middle of a huge financial—the worst recession in a century— and political crisis. This is in great part due to the fact that president Dilma Rousseff has been stripped of her duties for an impeachment trial. The interim government is being led by vice president Michel Temer, who himself also faces impeachment and has been investigated for briberies and kickbacks on two occasions. A massive corruption scandal at Petrobras, Brazil’s national oil company, is also adding to the instability. The country is also struggling with a Zika epidemic. Brazil is the hardest hit by the virus, and the state of Rio de Janeiro has reported the second-highest number of cases in the country. The U.S. Centers for Disease Control & Prevention has said there is little likelihood that any of the more than half-a-million attendees at the games will acquire the virus and carry it home. Despite this, some
athletes have withdrawn from the games because of the risk of contracting the virus. Brazilian government officials regret this “overreaction,” especially given that winter has arrived in Brazil thus the number of suspected cases has fallen dramatically. And as it is now typical of every Olympics, doping scandals are never far away from the headlines. Allegations arose claiming Russia had encouraged its athletes to use performance-enhancing steroids, which has resulted in the International Olympic Committee “reversing the presumption of innocence” for Russian athletes. They now have to prove to their respective international sports federations that they are clean. You can learn more about antidoping technology on page 26 and get the backstory of the Russian scandal in our latest edition of Periodic Graphics with chemistry educator and Compound Interest blogger Andy Brunning on page 28. The last straw is the pollution problems that are sure to be an issue for water sports at the Rio Games. Marina da Glória, the base for Olympic sailing and windsurfing events, is a large body of water fed by excrementand litter-filled streams and rivers, including one that pours past a wastewater treatment plant that was built in the 1990s but was never connected. According to Reuters, a team of researchers from the Federal University of Rio de Janeiro recently found antibiotic-resistant super bacteria—of a strain that’s associated with sewage that causes potentially lethal infections—on the beaches and in the lakes where swimming, rowing, and canoeing events will take place. Given that the theme of this year’s games is sustainability, it looks like officials have missed the mark. Given the buildup, the Rio games are set to be quite tumultuous and full of surprises. I think one of them will be Phelps.
Editor-in-chief @BibianaCampos
Views expressed on this page are those of the author and not necessarily those of ACS.
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C&EN | CEN.ACS.ORG | AUGUST 8, 2016
Reactions ▸ Letters to the editor Hazy memories A recent Science Concentrate featured a new mechanism for aerosol formation (C&EN, May 30, page 7). There is another photochemical process for developing haze events. In 1990, in Hilton Head, S.C., I presented a paper concerning carboxylic acids in acid rain at an international conference for the National Acid Precipitation Assessment Program. After listening to others, I was curious about carboxylic acids in haze. Thanks to high-performance liquid chromatography, it was determined that the main, indeed often the only, carboxylic acid
Note to readers C&EN will not publish an issue on Aug. 15, 2016. Watch for C&EN’s special double issue on Aug. 22 announcing this year’s Talented 12, a list of 12 young chemical scientists whose next moves you won’t want to miss.
How to reach us Chemical & Engineering News Letters to the Editor
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present in haze is oxalic acid. Because of the belief that this acid could result from the photochemistry of hydrocarbons, water vapor, and air, a reactor was constructed. After several hours, more than 40 compounds formed, indicating a pathway that did not generate carboxylic acid. A paper concerning this research was presented at the ACS national meeting in Denver in 1993. A friend, David Badger, jokingly suggested that oxalic acid can be formed from carbon dioxide and water. A reactor was constructed. CO2 and water were placed inside, and the ultraviolet lamp was turned on. I went to class, returned, and observed that a haze had formed. CO2 and water vapor in the presence of light from a low-pressure mercury vapor lamp had reacted to form oxalic acid. The reaction did not occur when a medium-pressure lamp was used. Oxalic acid is a major component of photochemical haze and only requires CO2 and water vapor in the presence of sunlight to form.
W. G. Sayre Castine, Maine
‘Ninja’ chemist After reading the Newscripts about chemists vying to appear on the TV show “American Ninja Warrior” (C&EN, June 20, page 40), I wanted to point out one more chemist who escaped the public eye because of some very unfortunate circumstances. Eli Lilly & Co. research chemist Thierry Masquelin (aka “the French Dragon”) was also selected to compete on the show that filmed in Indianapolis (where he has worked and lived for more than 20 years, conveniently). Sadly, he had a terrible fall during training a few weeks before competing, breaking numerous bones and tearing all the soft tissue in his shoulder; this is likely why he was not brought to your attention when researching this article. It would have been very entertaining to see him compete, as he is far bigger than most of the competitors I have ever seen on that show and quite a character! Maybe we will see him in next year’s competition after he heals all his injuries.
Chris Rito Indianapolis
▸ From the web Re: Chemist’s death Justine Roth, associate professor of chemistry at Johns Hopkins University, was found dead in her home on July 18 (C&EN, Aug. 1, page 38). She was 46. Online readers expressed grief over the loss and shared memories of Roth.
▸ cenm.ag/ justineroth
Profound sadness at the loss of a talented researcher who provided keen insight into biochemistry.
Brian Gibney via Facebook Justine Roth was an outstanding mentor and friend to her research students. She will be greatly missed. Thank you, Justine.
Daniel Cheney via C&EN’s website Justine Roth’s death will create a vacuum in research work, which I personally feel won’t be filled in the near future. Now, we, the researchers, have to highlight her precious work and good deeds so that her name remains luminous in the whole scientific world.
Muhammad Ayub via C&EN’s website This is quite a shock. I worked closely with Justine at UC Berkeley as a postdoc. ... Justine was so careful and methodical that her oxygen isotope experiments on electron transfer had more than five-significant-figure accuracy, at a time when I struggled to get the same result twice! ... As she was the most ambitious scientist I ever worked with, a small part of me was still relying on Justine to fix the global energy crisis from thermodynamic first principles, or even to discover new thermodynamic laws—she really was that capable.
H Pershad via C&EN’s website
Join the conversation. facebook.com/CENews @cenmag
AUGUST 8, 2016 | CEN.ACS.ORG | C&EN
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Concentrates Chemistry news from the week
▸ Highlights New electrode material gives Li batteries a boost Natural product helps obese mice slim down C–H functionalization diversifies amino acids Nobel Laureate Ahmed Zewail dies at age 70 GSK, Verily launch implantable device therapy firm Rio Olympics and Dow aim to leave low-carbon legacy Chemical safety board says refiner ignored problems Genetically modified wheat disrupts trade
6 6 7 7 10 11 14 14
ACS NEWS
China tops 48th International Chemistry Olympiad U.S. earns a gold, two silvers, and a bronze medal at the annual high school chemistry competition
China emerged as the theoretical exam plus top-performing team at a five-hour practical the 48th International laboratory exam. Some Chemistry Olympiad, of the questions related ▸ Number of students: 264 with each of its four to chemistry in Georgia, ▸ Participating countries: 67 team members scorfor example analyzing ▸ Medals awarded: 30 golds, 57 ing a gold medal. The samples of the country’s top-scoring gold medal silvers, 83 bronzes famous mineral water. ▸ Top performing countries: went to a high school “We actually tasted student on the Roma●●●● China the mineral water after nian team, which earned ●●●● Russia, Taiwan, the exam,” says bronze a total of three golds and Romania, Korea medalist Zilu Pan, who a silver. ●●●● Singapore, Iran, just graduated from CanIn all, 30 gold, 57 Thailand, India yon Crest Academy, in silvers, and 83 bronze San Diego, and is attendmedals were awarded during the annual ing Massachusetts Institute of Technology high school chemistry competition, which in the fall. “It had a very interesting taste was held from July 23 to Aug. 1 in Tbilisi, Georgia. Sixty-seven countries participated this year, with each country sending up to four students. The U.S. team, which is sponsored by the American Chemical Society, earned one gold, two silvers, and a bronze medal. “I’m very proud of the overall performance of the team, and we enjoyed the experience of being here in Georgia,” says head mentor Kelli Slunt, a chemistry professor at the University of Mary Washington. “The students were excellent ambassadors for the United States.” “I was really nervous throughout the closing ceremony,” says Alex Liu, a rising junior at the Village School, in Houston, who won the team’s gold medal. “When I heard my name being called, it was a combination of excitement and relief at the same time.” The competition consisted of a five-hour The U.S. team members, Pan (from left), Tian, Liu, and Tang, celebrate with their medals.
The olympiad at a glance
CRE DIT: CECILIA HE RNANDEZ
to it. I could taste the sulfur and the salts.” He and his fellow students also took an excursion to the region in Georgia where the mineral water is produced. Joyce Tian, a rising senior at Thomas Jefferson High School for Science & Technology in Alexandria, Va., who won a silver medal, says she’s proud of how she was able to handle intense pressure and have fun at the same time. The students agreed that the experience was more than about winning a medal. “Meeting all these students from other countries, sharing experiences, and talking about the future, it’s really a once-in-a-lifetime experience,” says Kevin Tang, a rising senior at Solon High School, in Ohio, who brought home a silver medal. The 49th International Chemistry Olympiad will take place in Thailand on July 6–15, 2017.—LINDA WANG
AUGUST 8, 2016 | CEN.ACS.ORG | C&EN
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Science Concentrates
Energy storage boost for lithium batteries New electrode material gives device an advantage over standard Li-ion systems A cross between lithium-ion and lithium-air batteries may lead to a new type of long-lasting energy storage device with high capacity (Nat. Energy 2016, DOI: 10.1038/nenergy.2016.111). The advance could help electric vehicles become more common and affordable. Lithium-air batteries look great on paper. In theory, they can pack roughly 10 times as much energy per weight as conventional lithium-ion batteries such as the ones that power cell phones. But the “air breathing” devices haven’t made it out of the lab yet because they fail quickly. These batteries are also inefficient electrically in that the voltage required to charge the battery is higher than that obtained while using the battery. In air-breathing batteries, the oxygen needed for electrochemical reactions comes
But the reaction forming Li2O2 is not fully reversible. As the oxide accumulates, it clogs the air-breathing electrode’s pores, making it difficult to get oxygen quickly and reversibly from outside the battery to the electrode surface. So MIT’s Ju Li, together with Jun Lu and colleagues at Argonne National Laboratory and Lu Qi of Peking University, came up with a battery system that takes advantage of Li2O2 but bypasses the problems of Li-air devices. They made a material consisting of nanosized patches of lithium oxide (Li2O) dispersed in a catalytic cobalt oxide matrix and used the material as the positive electrode in a sealed (non-air-breathing) Li-ion battery. On the basis of electrochemical and spectroscopy measurements, the team showed that during battery operation Li2O is converted reversibly to Li2O2 and LiO2. The battery boasts an energy storage capacity that approaches Li-air’s theoretical value and is nearly three times as high as that of Li-ion batteries. The capacity fell by only 1.8% after 130 charging cycles. In addition, the battery charges more efficiently than typical Li-air batteries. There is a worldAs depicted in this artistic rendering, one of the electrodes in a wide search for batnew high-capacity lithium battery consists of nanoscale patches teries that can surof lithium oxide (red and white) in a cobalt oxide matrix (black). pass Li-ion in terms of energy storage, from the air and reacts with lithium inside says the University of Liverpool’s Laurence the battery, forming lithium oxides, mainly J. Hardwick, who wrote a commentary in the lithium peroxide (Li2O2). That compound same issue of Nature Energy. The new study is one of the keys to Li-air batteries’ weight adds “a promising high-energy storage batadvantage: It has a much lower molecular tery system into the mix.” He adds that the weight than the transition-metal lithium detailed spectroscopy investigation reportoxides, such as LiCoO2, used in Li-ion ed here will greatly facilitate future developbatteries. ment of this system.—MITCH JACOBY
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DRUG DISCOVERY
Natural product helps obese mice lose weight When scientists discovered the hormone leptin in the 1990s, many thought studying its actions would lead to treatments for obesity. Leptin helps regulate hunger, and some scientists have proposed that obesity
H O
H H
HO
H O
O
OH
H
O Withaferin A
is the result of resistance to the hormone’s actions. Now, a team of researchers from Boston Children’s Hospital reports that a natural product can reverse that resistance in obese mice, helping the rodents slim down (Nat. Med. 2016, DOI: 10.1038/nm.4145). Umut Ozcan and colleagues found this so-called leptin sensitizer by searching through a database that contains cellular gene expression patterns induced by small molecules. The researchers were looking for a molecule that triggered a pattern like that of celastrol, a leptin sensitizer they had discovered previously. The molecule they found, withaferin A, reduced weight by 20 to 25% in obese mice fed a high-fat diet. The compound also improved glucose metabolism in the obese mice, suggesting it has antidiabetic effects. Not only are withaferin A’s effects in mice exciting, says Martin Myers of the University of Michigan Medical School, but so is the method used to find them. By looking for certain gene expression profiles, he says, the method could uncover potential antiobesity molecules that more traditional screens miss.—MICHAEL TORRICE
CRE DIT: DEMIN LIU/MOLGRAPHICS.COM
NANOMATERIALS
H
CATALYSIS
Iron catalysts diversify amino acids and peptides
N H R
Iron catalyst
HO
frequently difficult, sometimes alter amino acid stereochemistry, and have limited ability to modify amino acids already in peptides. M. Christina White and coworkers at the University of Illinois, Urbana-Champaign, in collaboration with chemists at Pfizer, now find that two previously discovered iron-based catalysts called Fe(PDP) and Fe(CF3PDP) can oxidize specific amino acids, either alone or in peptides, while maintaining native stereochemistry (Nature 2016, DOI: 10.1038/nature18941). Working with proline by itself or in peptides, they used the iron catalysts to hydroxylate the amino acid at the 5-position on its ring and then used other reactions to further modify the resulting 5-hydroxyproline intermediate. They used that approach to convert proline into 21 unnatural amino acids and to diversify a proline-containing tripeptide into eight modified tripeptides. “Peptides are very much in vogue in the
R´
N R
O Hydroxylated intermediate
O Proline
New method mimics peptidesynthesis enzyme complexes To create peptides with diverse types of bioactivity, microorganisms use multienzyme complexes called nonribosomal peptide synthetases (NRPSs). For example, bacteria make the antibiotic vancomycin this way. Iron-based enzymes in NRPSs oxidize and modify amino acids both before and after the complexes assemble the amino acids into peptides. A new technique enables chemists to diversify amino acids and peptides the way that NRPSs do. The approach, its developers say, could make it easier to discover new peptide-based therapeutics, dozens of which are already on the market or in testing. Chemists aren’t as good at diversifying peptides as microbes are. Researchers often must synthesize peptides with modified amino acids from scratch, a laborious and time-consuming process. There are a few ways to oxidize amino acids to functionalize the molecules, but these techniques are
R´
EDG
N R
R´
O
X RHN
R´
O An iron catalyst hydroxylates proline, alone or in a peptide, to a 5-hydroxyproline intermediate that can then be functionalized. Red shows modifications. EDG = electron-donating group, R = 4-nitrophenylsulfonyl or peptide, R´ = methoxy or peptide, and X = carboxyl, amine, alcohol, or olefin. pharma and biotech world as leads for new small-molecule therapeutics, so this elegant work is relevant to contemporary drug design,” comments Dalibor Sames of Columbia University. “Time will tell how generalizable this sort of platform will be,” says David R. Spring of the University of Cambridge. Nevertheless, the technique is “a remarkable development,” and the ability to site-selectively oxidize proline in complex peptides “is very exciting for chemists,” he says.—STU
BORMAN
OBITUARIES
Ahmed Zewail dies at age 70
CRE DIT: MITCH JACOBY/C&EN
Chemistry Nobel Laureate pioneered femtochemistry and promoted science education internationally Ahmed H. Zewail, the Linus Pauling Professor of Chemistry and a professor of physics at California Institute of Technology and the recipient of the 1999 Chemistry Nobel Prize, has died. He was 70. Zewail’s name is synonymous with femtochemistry, the branch of ultrafast laser spectroscopy he and his research group pioneered for interrogating chemical bonds on the timescale which they are formed and broken. In addition to that body of Nobel Prize-winning work, Zewail was also wellknown for his seminal studies on ultrafast electron microscopy for imaging molecules. The Egyptian-born researcher was also well-known for crisscrossing the globe, serving as an international science ambassador and a member of President Barack Obama’s Council of Advisors on Science & Technology. In that capacity, he promoted scientific
and educational collaborations between the U.S. and countries in the Middle East. In one show of solidarity with his native Egypt, Zewail quickly headed to the Middle East as the events of the Arab Spring unfolded in
Zewail
early 2011 on the streets of Cairo, Alexandria, and other Egyptian cities. While there, he promoted peaceful regime change and served as a moderator between students and government bodies. In another display of commitment to his native Egypt, he founded Zewail City of Science & Technology, a university and research center based in Cairo. It just recently began admitting students. “Ahmed Zewail was an extraordinary scientist who cared about the world and making a contribution to society as an Egyptian and as an American,” says Jacqueline K. Barton, Zewail’s longtime Caltech colleague and scientific collaborator. “He was a very wise man and a good friend of mine,” says Mostafa A. El-Sayed of Georgia Institute of Technology. “Ahmed was full of life and dedicated to everything he did. He will be sorely missed in the U.S and in Egypt.” Zewail won ACS’s highest honor, the Priestley Medal, in 2011. The society handed out its first annual Ahmed Zewail Award in Ultrafast Science & Technology in 2007.—MITCH JACOBY AUGUST 8, 2016 | CEN.ACS.ORG | C&EN
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Science Concentrates NANOMATERIALS
▸ NIST releases new antibody standard The National Institute of Standards & Technology has a repository of approximately 1,200 reference materials that scientists can purchase to calibrate their instruments and establish quality-control protocols. The newest reference material, a monoclonal antibody, may be the agency’s most extensively characterized yet. The Y-shaped protein, which NIST released in late July, has undergone a battery of tests
NIST’s new monoclonal antibody standard is shipped on dry ice and stored at –80 °C. to comprehensively assess its composition, purity, and long-term stability. The reference material—dubbed NIST RM 8671—will give biopharmaceutical companies, technology developers, and regulators a common substance for comparing the performance of existing analytical technologies and for testing new ones. The extensive characterization is the outcome of more than three years of collaboration between NIST and the biopharmaceutical industry, says John Schiel, the NIST chemist who led the effort. The reference material, which costs $858 for 800 µL of a 10 mg/mL solution, is made of an immunoglobulin G antibody donated by MedImmune. Richard Rogers, a scientist at Just Biotherapeutics, is leading a consortium that hopes to replace many of the quality-control assays that biopharma companies usually perform when releasing protein-based products with a so-called multi-attribute method based on mass spectrometry. He plans to use the NIST standard to evaluate the method.—CELIA ARNAUD
VACCINES
▸ Vaccine candidates protect monkeys from Zika Last week, the Centers for Disease Control & Prevention urged pregnant women and
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C&EN | CEN.ACS.ORG | AUGUST 8, 2016
Off-the-shelf nanotubes for space telescopes Telescope mirrors made with carbon nanotubes could soon turn small satellites known as CubeSats into space-based observatories. Researchers at Goddard Space Flight Center led by Theodor Kostiuk and Peter C. Chen are now characterizing the mirrors’ optical performance over a range of wavelengths, NASA announced last month. And should the mirrors survive upcoming terrestrial tests mimThe aluminum-coated icking the thermal and mechanical stresses nanotube mirror rests at the of spaceflight, the optics would be available back of a 30-cm-long metal to use aboard CubeSats to snoop on nearby frame, which is about the comets, asteroids, moons, and planets, Kostisize of a standard CubeSat. uk says. To make the mirrors, the researchers first pour a mixture of epoxy and multiwall carbon nanotubes, both commercially available, onto a smooth mold. The nanotubes act like rebar, frustrating the epoxy’s natural tendency to shrink as it hardens. Thus, the epoxy-nanotube composite faithfully reproduces the mold. The researchers then coat the hardened composite with a reflective layer of aluminum. This scalable process not only allows NASA to create identical mirrors for CubeSats on the cheap, Chen says, but it’s also the first step toward establishing nanotubes as an advanced material for larger space telescopes.—MATT DAVENPORT
Researchers at Walter Reed Army Institute of Research prepare a Zika vaccine candidate. their partners to avoid a neighborhood north of Miami where Zika virus is known to be circulating. Zika has been linked to the neurological condition microcephaly in babies born to mothers infected with the virus. Now, scientists led by Dan H. Barouch of Beth Israel Deaconess Medical Center and Harvard Medical School report that vaccine candidates that previously provided protection against Zika virus in mice also work in
rhesus monkeys— an animal model that’s a good predictor for humans (Science 2016, DOI: 10.1126/science. aah6157). The researchers studied three different types of vaccine candidates and found all to be effective against Zika strains. One vaccine candidate prepared from purified inactivated virus, which was developed by Barouch’s collaborators at Walter Reed Army Institute of Research, proved to be particularly potent. The researchers hope to begin Phase I clinical trials of the vaccine candidates in humans later this year, and the Army recently signed an agreement with Sanofi Pasteur to explore larger scale manufacture of the vaccine candidate made from purified inactive virus. In June, a different Zika vaccine candidate, from Inovio Pharmaceuticals and GeneOne Life Science, was the first to be approved by the U.S. FDA for Phase I clinical trials. The National Institute
CRE DIT: NASA/W. HRYBYK (METAL FRAME); WRAIR (RESEARCHERS); MATTHEW DELORME (BOTTLE)
BIOLOGICS
of Allergy and Infectious Diseases has another vaccine candidate in Phase I trials (see page 10).—BETHANY HALFORD
ENERGY STORAGE
▸ Hybrid power source delivers highenergy bursts Fuel cells that run on glucose could be ideal alternatives to batteries for powering implanted medical devices, such as pacemakers and brain stimulators. But fuel cells alone cannot generate the quick, high-energy pulses such devices need. Researchers have now made a compact power source that delivers such bursts by combining a glucose fuel cell with a supercapacitor (ACS Energy Lett. 2016, DOI: 10.1021/acsenergylett.6b00225). Shelley D. Minteer of the University of Utah and colleagues coated carbon electrodes with
NATURAL PRODUCTS
An enantioselective synthesis of (+)-psiguadial B The leaves of the common guava plant Psidium guajava have long been used as an herbal remedy. Natural products extracted from these leaves include (+)-psiguadial B, which is toxic to liver cancer cells. (+)-Psiguadial B possesses the kind of structure that makes synthetic H chemists swoon. It’s loaded with strained O H rings and stereocenters—perfect for trying out some new chemistry. Caltech chemists H OH O led by Sarah E. Reisman now report the first enantioselective total synthesis of (+)-psiguaO dial B (J. Am. Chem Soc. 2016, DOI: 10.1021/ H jacs.6b07229). The chemists completed the OH H synthesis in just 15 steps, starting from a simple diazoketone. Reisman’s group first set out to make the strained portion of the molecule, (+)-Psiguadial B which includes a fused trans-cyclobutane ring. A key transformation they developed en route was a tandem reaction combining a Wolff rearrangement and an asymmetric ketene addition—the first time this combo has been reported. This step creates the cyclobutane portion of the molecule while incorporating an important directing group for a subsequent C–H functionalization reaction. The chemists hope they can use this strategy to make other molecules with trans-cyclobutane rings.—BETHANY HALFORD
GEOCHEMISTRY
CRE DIT: SHE LL EY MINTE ER/U. UTAH (FUE L CEL L); SHUTTERSTOCK (BRIDGE )
▸ Concrete creep mechanism explained A coin-sized hybrid device that integrates a supercapacitor into a glucose fuel cell (left) could power medical implants.
enzymes that catalyze redox reactions to produce an electric current. The anode is loaded with glucose dehydrogenase and coated with polyethylenimine, which stores charge and acts as the supercapacitor. As glucose becomes oxidized, electrons travel through an external circuit to the cathode, which is coated with bilirubin oxidase. Some of the electrons charge the capacitive polymer layer. During spikes in power demand, the supercapacitor discharges, providing the needed high-energy bursts. The researchers encased the device in a metal mesh so that blood can reach the electrodes and provide a constant supply of glucose. The new device has a capacitance of 300 faradays per gram, more than four times as high as previous biobased supercapacitors delivering comparable voltage.—PRACHI PATEL, special to C&EN
in the world. Scientists have proposed models for concrete creep mechanisms, but none have been able to explain all of the physical manifestations of creep. In the new work, the researchers combined experimental data, such as vertical scanning interferometry, which measures nanoscale mineral dissolution, with molecular dynamics simulations of the behavior of various CSH compositions. They showed that CSH grains dissolve under high stress, and re-precipitate at low stress. They also identified CSH variants that are less likely to creep.—ELIZABETH WILSON
Concrete is ubiquitous as a building material, but it suffers from “creep,” long-term deformations caused by its own weight, that damage its integrity and make it susceptible to cracking and crumbling. Now, scientists have evidence this creeping phenomenon stems from nanoscale dissolving of concrete’s primary phase, calcium silicate hydrate (CSH) grains, under high stress (J. Chem. Phys. 2016, DOI: 10.1063/1.4955429). The discovery, by a team led by Gaurav Sant, Mathieu Bauchy, and Isabella Pignatelli at UCLA, could allow further study to devise concrete compositions that are more resistant to creep. Concrete—various mixtures of sand or gravel with a binder and water—has been Concrete creep leads used as a building material to crumbling, as for thousands of years, and seen in this bridge in today, next to water, it’s the Ottawa, Ontario. most widely used material
AUGUST 8, 2016 | CEN.ACS.ORG | C&EN
9
Business Concentrates INORGANIC CHEMICALS
GSK and Verily launch Galvani Bioelectronics Drug giant and tech firm form a company to create therapies that use implantable devices GlaxoSmithKline has joined with Verily Life Sciences to set up Galvani Bioelectronics, which will focus on treating chronic illnesses by controlling electrical impulses in the body. GSK and Verily, the former Google Life
Galvani Bioelectronics envisions putting electronic devices around nerve bundles to treat diseases as depicted in this drawing. Sciences business, will initially invest up to $718 million over seven years to support R&D at Galvani. Having made a concerted push into the bioelectronics area in 2012, GSK will now put its in-house efforts into Galvani for a 55% stake. The start-up will be housed at GSK’s Stevenage, England, R&D site with research also conducted in South San Francisco. Kris Famm, GSK’s vice president of bioelectronics R&D, will become Galvani’s president. Galvani will combine GSK’s capabilities with Verily’s technical expertise in miniaturizing low-power electronics and in developing implantable devices, data analytics, and software for clinical applications. Galvani will initially employ about
30 scientists, engineers, and clinicians. GSK says it has already seen encouraging proof of principle results in animal models in a range of diseases. And it anticipates that the first bioelectronic therapies could be ready for approval within 10 years. To achieve this, Galvani will focus on showing clinical evidence in inflammatory, metabolic, and endocrine disorders, including diabetes. Although neurostimulators are available to treat epilepsy, pain, and other conditions, GSK envisions much tinier devices attached directly to nerves. These devices will be designed with better clinical insight and more precise neural control, the company claims. Ultimately, the goal is to close the therapeutic loop by having devices that can measure conditions, analyze data, and adjust treatment as needed. To advance its bioelectronics agenda, GSK spent $50 million in 2013 to set up Action Potential Venture Capital, which has invested in at least five companies. Last month, one of these, SetPoint Medical, reported clinical trial data demonstrating that stimulating the vagus nerve with an implantable bioelectronic device inhibits cytokine production and significantly reduces rheumatoid arthritis symptoms (Proc. Natl. Acad. Sci. USA 2016, DOI: 10.1073/pnas.1605635113). GSK has also established a network of about 50 research collaborations. In late 2014, it launched a $5 million Innovation Challenge Fund to support academic and small company bioelectronics-related R&D teams. Three finalist teams remain and GSK hopes to award a $1 million prize by year-end.—ANN THAYER
VACCINES
The National Institute of Allergy & Infectious Diseases has begun a clinical trial of a vaccine against the Zika virus. The vaccine contains a small, circular piece of DNA—called a plasmid— containing genes that code for Zika proteins. At least 80 healthy volunteers in the U.S. will get the vaccine to see if it’s safe and can generate an adequate immune response. More than 6,400 cases of Zika have been reported in the U.S. and its territories, including 15 cases in Florida.
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Deals flourish in sulfur chemicals The normally quiet sulfur chemicals industry is seeing a flurry of merger and acquisition activity— and more may be in the offing. Chemours has sold its sulfur products business to Veolia for about $325 million. And Ineos has agreed to acquire Calabrian, a U.S. sulfur chemicals specialist, from the private equity firm SK Capital Partners for an undisclosed sum. Chemours sold its business, which makes sulfur chemicals and recycles spent sulfuric acid for the refining industry, as part of a slimming-down process that started after its spin-off from DuPont last year. Veolia, a French resource management firm, says the purchase expands its offerings to refining customers, which use sulfuric acid as an alkylation catalyst. Ineos, meanwhile, is getting a business that has expanded considerably since 2011 when SK Capital injected cash into Calabrian. When Calabrian’s “production facility in eastern Canada comes on-line at yearend, Calabrian’s earnings will have tripled since our acquisition,” says SK Capital Managing Director Barry Siadat. For Ineos, the business complements a sulfur chemicals facility in the U.K. and a sulfuric acid plant in northern Spain that it acquired in December 2015. Ineos also is a shareholder in the U.S. inorganic chemicals maker PQ, which in May completed a merger with Eco Services, a former Solvay business that recycles spent sulfuric acid. Ineos declines to discuss whether the next step might be to merge its sulfur chemicals business with PQ, saying its current focus is on integrating Calabrian.—
MICHAEL MCCOY
CRE DIT: GLAXOSMITHKLINE (CHIP); NATIONAL INSTITUTE OF ALL ERGY AND INFECTIOUS DISEASES (VACCINE)
START-UPS
SUSTAINABILITY
Rio Olympics teams with Dow to leave a low-carbon legacy New materials and upgraded manufacturing to help Brazil reach its 2025 greenhouse gas goal As athletes from around the world bring their gold medal dreams to Rio de Janeiro this week, the host country is putting forward its own challenge goal. Having chosen “sustainability” as a theme for this year’s games, the Rio 2016 Organizing Committee hopes to promote low-carbon technologies that will cut the 2 million metric tons of carbon dioxide equivalents associated with the games by 2026. Organizers want strides made in Rio to be a catalyst for further greenhouse gas reductions throughout Brazil and Latin America. The committee is relying on a six-yearold partnership with Dow Chemical to achieve its target. The U.S. firm was named the official chemical company of the Olympic Games
Olympics organizers hope the theme of sustainability gains momentum that will carry beyond the games.
in 2010. Acting in that capacity at the 2012 London games, Dow supplied infrastructure materials, notably an energy-efficient polyolefin elastomer to replace polyvinyl chloride. Dow and Olympics organizers launched a program to mitigate the carbon footprint associated with the 2014 Sochi Winter Olympics, and they hope to expand that effort beyond the games this year to assist Brazil in meeting its goal, stated at last year’s Paris climate talks, of reducing greenhouse emissions by 37% from 2005 levels by 2025. “We realized there was an opportunity in Rio to help with mitigation efforts by creating what the Olympic Games are about—a legacy,” says Nicoletta Piccolrovazzi, tech-
nology director for Olympic and sports solutions at Dow. Among the technologies being introduced at the Rio Olympics are microfoam flexible packaging, bonding materials for lightweight vehicles, and waterborne road marking paints. Piccolrovazzi says Dow has been working with customers in Brazil on manufacturing improvements that lower greenhouse gas emissions. Delivery of games with a minimal carbon footprint is a big part of Brazil’s sustainability strategy, says Tania Braga, head of sustainability, accessibility, and legacy for the Rio 2016 Organizing Committee. “Most importantly,” she adds, “we were able to create momentum by engaging key industries in Brazil and in Latin America towards a more sustainable way to operate.”—RICK MULLIN
RARE DISEASE
Pfizer acquires Bamboo Therapeutics Deal brings gene therapy technology and key manufacturing capabilities Further bolstering its rare disease unit, prompt the production of dystrophin, a proPfizer has paid $150 million to acquire gene tein missing in people with Duchenne mustherapy-focused Bamboo Therapeutics. The cular dystrophy (DMD). Pfizer already has drugmaker, which earlier this year took a a myostatin inhibitor, which could promote 22% stake in Bamboo, could shell out anothmuscle growth in DMD patients, in Phase II er $495 million to investors in the biotech if studies. its gene therapies reach the market. Bamboo was spun off in 2014 from Asklepios Biopharmaceutical, a biotech Pfizer has made multiple rare disease deals founded by three University of North since creating a rare disease unit in 2010. Carolina, Chapel Hill, scientists with ex2010 Acquires FoldRx pertise in using adeno-associated viruses to deliver genes that teach cells how to • Links with Zacharon for lysosomal storage diseases 2011 • Licenses Glycomimetics’ sickle cell treatment make missing or improperly functioning with Cystic Fibrosis Foundation to support CF proteins. 2012 Joins drug development Through the purchase, Pfizer gains Repligen’s spinal muscular atrophy treatment 2013 Licenses preclinical and clinical gene therapies, (returned in 2015) many of which complement the drug • Acquires Opko Health’s long-acting growth hormone 2014 • Creates gene therapy pact with Spark Therapeutics firm’s growing rare disease pipeline. For example, the deal brings Pfizer a therapy 2016 Acquires Bamboo Therapeutics that could deliver a gene sequence to
CRE DIT: SERGIO MORAES/REUTERS/NEWSCOM
Portfolio building
But the attraction of Bamboo is about more than just its gene therapy pipeline, says Greg LaRosa, chief scientific officer of Pfizer’s rare disease unit. “Most importantly, they can manufacture gene vectors in amounts you can actually provide for clinical trials.” For a disease such as DMD, “a lot of virus is going to be needed,” LaRosa points out. Bamboo bought its vector manufacturing facility from UNC in January and expects to be able to start a clinical trial for its DMD therapy in the second half of 2017. The biotech firm has already produced a gene therapy for giant axonal neuropathy, a rare nervous system disease, that is being tested in a clinical trial run by the NIH. Bamboo has received substantial support from rare disease advocacy groups. CureDuchenne Ventures, for example, was one of several investors in the biotech’s first major round of funding—for $49.5 million—in January.—LISA JARVIS AUGUST 8, 2016 | CEN.ACS.ORG | C&EN
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Business Concentrates POLYMERS
▸ Merck KGaA widens its LCD offering Merck KGaA, the world’s top producer of liquid crystals used in displays, is strengthening its stake in the business. The German firm has signed a license agreement with the British firm Nanoco allowing Merck to produce cadmium-free quantum dots, which are used to enhance color in liquid crystal displays. Separately, Merck says it will spend $17 million to build a plant that
LyondellBasell plant to debut polymer process LyondellBasell Industries is moving forward with plans to build a high-density polyethylene (HDPE) plant on the U.S. Gulf Coast. The plant will have 500,000 metric tons of annual capacity when it opens in 2019 and be the first to use the company’s new Hyperzone technology. The process uses a twostage, gas-phase reactor that constructs a multimodal resin. The first stage, explains Dan Coombs, Lyondell’s executive vice president of global olefins and polyolefins technology, imparts processability by giving the polymer an optimal molecular weight. The second stage’s multizone reactor controls reaction conditions and the addition of comonomers. The company says Hyperzone technology offers improved stress crack resistance as well as a better balance between stiffness and impact strength than conventional HDPE. Target markets include pipe and blow-molded objects such as laundry detergent bottles. The company ultimately aims to license the technology.—ALEX TULLO
BIOBASED MATERIALS
▸ Lenzing boosts cellulosic fibers Merck researcher Harald Seibert studies the surface structure of an LCD substrate with an atomic force microscope. produces liquid crystal windows. In June 2014, Merck acquired Peer+, a Dutch firm specializing in such windows, which can be electrically activated to control external light.—JEAN-FRANÇOIS TREMBLAY
MERGERS AND ACQUISITIONS
▸ Alpek beefing up polyester presence Mexican chemical maker Alpek has made a small polyethylene terephthalate (PET) acquisition in Canada and may make a big one in Brazil. Alpek’s U.S. subsidiary, DAK Americas, has bought control of Selenis Canada, which operates a small PET plant in Montréal, from Portugal’s IMG Group. Meanwhile, Alpek is in exclusive negotiations to buy Petroquímica Suape, a PET complex in Pernambuco, Brazil, from Brazilian state oil company Petrobras. Opened in 2013 the complex makes PET, the PET raw material purified terephthalic acid, and polyester filament. Brazil’s economic downturn forced Petrobras to take a $1.1 billion write-down on the plants in 2014 and $200 million last year. —ALEX TULLO
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Lenzing is spending more than $110 million to expand its output of specialty cellulosic fibers in Heiligenkreuz and Lenzing, Austria. Scheduled to come online over the next two years, the 35,000 metric tons of annual capacity will satisfy growing demand, Lenzing says. Although most of the firm’s fibers are made from wood pulp, last month it launched a fiber made from recycled cotton fabric. Starting with cotton waste, Lenzing says, reduces the environmental impact of cellulosic fiber production.—MARC REISCH
BIOBASED CHEMICALS
▸ Energy Department funds bioproducts
recovering mixed methoxyphenols from biocrude.—MARC REISCH
BUSINESS
▸ Solvay adds capacity and exits a business Solvay plans to increase capacity for one business and divest another. At its Chicago Heights, Ill., plant, the firm is adding 10,000 metric tons of annual capacity for highly dispersible silica. The investment follows recent expansions in Poland, Brazil, and South Korea to supply customers of the fuel-saving tire additive. Separately, Solvay will sell its chlorine and peroxide derivatives site in Bussi sul Tirino, Italy, to the Italian firm Caffaro. Solvay says it will continue to market organic peroxides made there.—MARC REISCH
SPECIALTY CHEMICALS Three early-stage projects to advance biochemical and biofuel production have won up to $11.3 million, combined, from the U.S. Department of Energy. In one project, Dow Chemical, LanzaTech, and Northwestern University will develop a process for the bioconversion of biomass-derived syngas to C6-C14 fatty alcohols. Separately, Amyris will cooperate with Renmatix and Total New Energies on converting cellulosic sugar-based farnesene into consumer products and fuels. And Research Triangle Institute will partner with Arkema and engineering firm AECOM to investigate
▸ Innospec acquires Huntsman surfactants Innospec has agreed to acquire Huntsman Corp.’s European surfactants business for $225 million. Based in Belgium, the business has annual sales of around $230 million from plants in France, Italy, and Spain. Innospec says the purchase is in keeping with its desire to expand in the personal care sector. Huntsman says it is committed to its remaining surfactants businesses in
CRE DIT: MERCK KGAA
MATERIALS
PHARMACEUTICAL CHEMICALS
the U.S. and Australia, which it describes as being backward integrated into essential feedstocks.—MICHAEL MCCOY
▸ Cambrex rides a wave to further expansion
EMPLOYMENT
▸ NewLink and Tokai will cut jobs Setbacks in late-stage cancer clinical trials have led to job cuts at NewLink Genetics and Tokai Pharmaceuticals. NewLink will cut about 100 jobs, or more than 40% of its staff, as it winds down work on the cellular immunotherapy algenpantucel-L, which failed to show any effect against pancreatic cancer. The firm will focus on developing its IDO pathway inhibitor, indoximod, in multiple cancers. Likewise, Tokai will reduce its workforce by about 60% to just 10 full-time employees. The company recently halted a Phase III prostate cancer trial of its small-molecule drug galeterone. The company says it will explore options for galeterone.—ANN THAYER
POLYMERS
▸ Chevron Phillips completes pilot unit Chevron Phillips Chemical has completed a polyethylene pilot plant at its R&D facility in Bartlesville, Okla. The plant is based on CP Chem’s MarTech technology, which is used in 80 polyethylene plants operating in
Chemical engineering intern Joshua Henderson in front of CP Chem’s new pilot plant. 16 countries. It will test new catalysts and polymers.—ALEX TULLO
PHARMACEUTICALS
▸ Takeda plans layoffs in R&D reorganization Takeda Pharmaceutical will eliminate an unspecified number of jobs as part of an R&D revamp. The company says it plans to centralize research in the U.S. and Japan, suggesting that its R&D center in the U.K., which employs 400, is threatened. Takeda’s research center in Shonan, Japan, on which it recently spent $1.8 billion, will concentrate on the central nervous system and regenerative medicine. The company also will continue to research vaccines, gastroenterology, and oncology. The layoffs and related restructuring will cost $740 million over the next two years, the firm anticipates.—JEAN-FRANÇOIS TREMBLAY
Business Roundup
CRE DIT: CHEVRON PHILL IPS
▸ Celanese has ceased making monomethylamine in Cangrejera, Mexico, after a review determined that continued production was no longer a “viable business option.” The company has redirected monomethylamine equipment towards dimethylamine and trimethylamine. ▸ The Chemical Heritage Foundation has named former British Museum director Robert Anderson as its interim president. Predecessor Carsten Reinhardt, who headed CHF since 2013, is return-
Following a $50 million expansion of its active pharmaceutical ingredients facility in Charles City, Iowa, earlier this year, fine chemicals maker Cambrex is already considering its next expansion at the site as well as improvements at plants in Sweden and Italy. The firm said on an earnings conference call that it expects to announce the projects, likely to cost about $20 million, by the end of the year. CEO Steven Klosk noted that the new capacity in Charles City is filling up quickly.—RICK MULLIN
ing to Germany and will be a history of science professor at Bielefeld University. ▸ Envergent Technologies, a joint venture of UOP and Ensyn, has begun building a facility in Port-Cartier, Quebec, that will make renewable fuels out of forest residues. The firm says fuels made with its RTP fast thermal conversion process have a carbon intensity that is 70% less than petroleum-based fuels. ▸ Sumitomo Chemical and Zeon Corp. are studying the
ONCOLOGY
▸ Amgen strikes immunotherapy deal Amgen will pay Advaxis $40 million up front and buy $25 million in Advaxis stock for rights to the personalized cancer immunotherapy ADXS-NEO. The treatment is created by sequencing a patient’s healthy and cancer cells to identify neoepitopes, or markers on antigens, that are most likely to prompt an immune response. Advaxis then uses an engineered strain of bacteria to deliver neoepitope peptides directly into cells that tell the immune system to recognize and combat tumor cells. The companies expect to start the first clinical trials of ADXS-NEO next year.—LISA JARVIS
combination of their solution styrene-butadiene rubber businesses. A joint venture, the Japanese companies say, would accelerate new product development and enhance cost competitiveness. ▸ JSR will sell its line of Opstar coating materials, used primarily to impart anti-reflective properties to liquid crystal displays, to Arakawa Chemical Industries. The business has been struggling due to poor market conditions, JSR says. ▸ Avrobio has raised $25 million in its first formal round of funding. The cash will be
used to advance gene therapies for Fabry disease and acute myeloid leukemia. Avrobio inserts a new, functional copy of a faulty gene into a patient’s own stem cells, which are then given back to the patient. ▸ Evelo Biosciences will work with Mayo Clinic researchers on microbiome-based therapies for cancer. Using samples from patients, the partners will isolate and characterize cancer-associated bacteria that might be used to activate the immune system against cancer. Mayo Clinic has a financial interest in Evelo.
AUGUST 8, 2016 | CEN.ACS.ORG | C&EN
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Policy Concentrates BIOTECHNOLOGY
Refinery ignored safety risks Safety Board criticizes Tesoro for acid leaks The Tesoro refinery in Martinez, Calif., for years ignored safety problems and fostered a weak safety culture, the U.S. Chemical Safety Board says in a report released on Aug. 2. Board officials urged Tesoro and other refiners to elevate the importance of process safety and encouraged state and local regulators to frequently conduct preventive safety inspections of the facility.
A piping failure during a maintenance operation to replace a sulfuric acid sampling system injured workers at the Tesoro Refinery in Martinez, Calif. Triggering CSB’s report and investigation were incidents in February and March 2014 at the facility’s alkylation unit, which carries out a process common at U.S. refineries. Tesoro’s unit uses sulfuric acid as a catalyst to reformulate low-value hydrocarbons, such as propane and butane, to produce a premium, high-octane gasoline blend stock. The first of the two accidents was the result of a piping failure that released some 38,000 kg of sulfuric acid over two hours and burned two employees. Tesoro initially characterized the accident as minor and refused to allow CSB to investigate. In the second incident a month later, two contract workers were sprayed and burned with sulfuric acid at the same unit. The two incidents followed 13 similar sulfuric acid accidents at the facility since 2010, CSB says. It suggests the company failed to learn from past mistakes and allowed accidents to continue. The second incident, CSB notes, had similarities to a 1999 incident at the refinery in which four workers were killed. Much of CSB’s report focuses on the February 2014 accident which occurred in piping for the plant’s sulfuric acid sampling system. Tesoro had purchased and intended to install a new, closedloop, so-called inherently safer acid sampling system that is similar to those used at other California refineries. However, the company claimed the system was unreliable, CSB says, and never installed it. Instead Tesoro slightly upgraded its existing sampling system, which requires workers who draw samples to wear personal protective gear to counter the expected release of sulfuric acid vapors. Tesoro officials would not comment on the specific accident or decision not to install inherently safer technology. They, however, cited unspecified “inaccuracies” in CSB’s report.—JEFF
JOHNSON, special to C&EN
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Genetically modified wheat disrupts trade Japan, S. Korea halt U.S. wheat shipments Japanese and South Korean authorities have put a hold on purchases of western white wheat from the U.S. for food use and stopped distribution of already purchased U.S. wheat. The move comes in response to a farmer’s discovery of 22 genetically modified wheat plants growing in an unplanted field in Washington state. It is unclear how the wheat ended up in the Washington field. The Department of Agriculture has not approved the cultivation or sale of any genetically modified wheat varieties in the U.S. USDA confirmed the discovery on July 29, identifying the wheat as Monsanto’s MON71700, containing the CP4-EPSPS protein. This molecule, an enzyme, helps plants tolerate the herbicide glyphosate, the active ingredient in Monsanto’s Roundup and many generic herbicide formulations. Organizations representing the wheat industry—U.S. Wheat Associates and the National Association of Wheat Growers—are downplaying the significance of the incident. The groups expect that testing will show there is no detectable MON71700 in the U.S. wheat supply and that exports to Japan and South Korea will start again quickly. “The materials needed to create the test assay are in Japan, and it should only take two to three weeks” for the Japanese government to start testing, they say. “The results will end the suspension very soon,” the groups predict. The test was developed by Monsanto and validated by USDA to identify MON71700 in grain shipments. It is available to international trading partners to test U.S. wheat, USDA notes. USDA officials say there is no evidence that the genetically modified wheat made its way into commerce. And if the grain had made its way into the food supply, the Food & Drug Administration says, “it is unlikely that the wheat would present any safety concerns” because of the small number of plants involved. The variety is similar, but not identical, to genetically modified wheat found growing in Oregon in 2013. Some food safety advocates suggest it could have been because of lax oversight of field trials of MON71700 conducted by Monsanto from 1998 to 2001. Because of pressure from such groups, USDA this year beefed up its regulations to require a permit instead of just a notification to conduct field trials with genetically modified wheat.—BRITT ERICKSON
CRE DIT: CSB (PIPES); SHUTTERSTOCK (WHEAT)
INDUSTRIAL SAFETY
Policy Concentrates POLICY POLLUTION
▸ EPA curbs formaldehyde emissions from wood products A final rule from EPA is aimed at reducing people’s exposure to formaldehyde vapors from domestic and imported composite wood products. The rule meets a 2010 requirement set by Congress in the Formaldehyde Standards for Composite Wood Products Act, which directed EPA to set national standards. The regulation, which takes effect next year, will require manufacturers to comply with new testing and certification requirements. EPA says it worked with the California Air Resources Board to draft measures that are consistent with the state’s requirements, which were adopted in 2008. “The new rule will level the playing field for domestic manufacturers who have a high rate of compliance with the California standard and will ensure that imported products not subject to California’s requirements will meet the new standard and thus not contain dangerous formaldehyde vapors,” says Jim Jones, EPA assistant administrator for chemical safety and pollution prevention.
Calling for studies on how to diversify science workforce The rigorous, evidence-based approaches used in research should be applied to increasing diversity in science, according to three higher education organizations. The Association of Public & Land-grant Universities, the Coalition of Urban Serving Universities, and the Association of American Medical Colleges studied the lack of diversity in the biomedical sciences. Their report says individual universities are trying their own diversity initiatives, but a broader approach would allow evidence about successful interventions to be more widely shared. Among its recommendations, the report suggests a focus on graduate school programs that can reduce what is called stereotype threat, which is when individuals feel judged with stereotypes about their minority group. It also suggests studying ways to encourage more minority graduate students to continue in postdoctoral studies and, eventually, academia. One change that might work now, the report says, is using holistic review to get a more diverse pool of graduate students. The strategy, which focuses on an applicant’s entire experience rather than just test scores or grades, has increased diversity in medical schools.—ANDREA WIDENER
Formaldehyde is common in wood product adhesives. It has been linked to cancer and respiratory problems in humans.—GLENN
HESS, special to C&EN
CRE DIT: SHUTT ERSTOCK
OVERHEARD
“It is not the richest countries that invest in science and technology—it is the countries that have invested in science and technology that are now the richest.” Mariano Barbacid, the molecular biochemist who discovered the first oncogene, quoted recently in the Spanish newspaper El Mundo.
PESTICIDES
▸ Illegal dicamba use damaging soybeans in U.S. More than 100 farmers in Arkansas, Missouri, and Tennessee have filed complaints against their neighbors for illegally spraying the herbicide dicamba (3,6-dichloro-2-methoxybenzoic acid) on soybeans genetically modified to tolerate the chemical. The unhappy farmers claim that the herbicide drifted onto their property, damaging soybeans that were not engineered to tolerate it. Small amounts of dicamba cause soybean leaves to curl into cuplike shapes. Earlier this year, Monsanto began selling soybeans under the name Xtend that tolerate both dicamba and the herbicide glyphosate. The soybeans were developed because many weeds are resistant to glyphosate. But EPA has not approved the use of dicamba on soybeans, so U.S. farmers cannot legally spray the chemical on Xtend soybeans. EPA proposed in April to allow such uses for five years. The agency would then review whether weeds are becoming resistant to dicamba before reapproving such uses. EPA expects to decide on the proposal by early fall. USDA declared last year that Extend soybeans are unlikely to pose a risk to other plants, paving the way for their entry into the market.—BRITT ERICKSON AUGUST 8, 2016 | CEN.ACS.ORG | C&EN
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Features
TOXICOLOGY
Making sure chemical toxicity tests don’t miss metabolites BRITT E. ERICKSON, C&EN WASHINGTON
O
nce hailed as a safe alternative to the persistent organochlorine insecticide DDT, methoxychlor was widely used for decades to fight flies, mosquitoes, roaches, and other household pests. It was also extensively applied to fruits and vegetables, grains, and livestock. But after laboratory animal studies linked the substance to developmental and reproductive side effects—including miscarriages, reduced fertility, and small litter size—regulators took action. The European Union banned sales of methoxychlor in 2002 and the U.S. followed suit in 2003. Without data from animal studies, regulators would have likely missed the adverse effects of methoxychlor. The insecticidal chemical itself is relatively benign. Once it enters the body, however, metabolic enzymes in the liver convert the chemical into 2,2-bis(p-hydroxy-
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EPA is creating lids that fit on 96-well (above, top) and 384-well (above, bottom) plates. The prongs are coated with a gel-like substance containing liver metabolic enzymes that are inserted into the wells on the microplate to produce likely metabolites.
phenyl)-1,1,1-trichloroethane (HPTE), a substance with estrogenic activity. This metabolite disrupts the body’s endocrine system. Compounds such as methoxychlor present a major challenge for regulators who are hoping to reduce the number of animal studies needed to demonstrate the safety of chemicals. They pin big hopes on high-throughput human cell-based assays that would replace slow and costly in vivo animal studies for evaluating chemical toxicity. Standing in their way, however, is the fact that such cell-based assays can’t yet detect the effects of unrecognized metabolites. “When a chemical comes into your body, the first thing your body will do is send it to the liver,” says Kevin Crofton, deputy director of the National Center for Computational Toxicology at the U.S. Environmental Protection Agency. “The liver is going to
recognize it as foreign, and try to chew it up and spit it out.” During that metabolic process in the liver, chemicals are often converted into less hazardous compounds. But sometimes, as in the case of methoxychlor, they are converted into more toxic compounds. If scientists rely on an assay that doesn’t account for metabolism, “what if we put the chemical in there and there is no effect?” Crofton asks. Compounds such as methoxychlor, which are not themselves toxic but give rise to toxic metabolites, may appear safe in such an assay. Several research groups are trying to solve this problem. They are developing tools that could be easily bolted onto existing human cell-based high-throughput assays to monitor effects from both parent chemicals and their metabolites. EPA launched a challenge earlier this year
CRE DIT: EPA
EPA looks to incorporate metabolism into high-throughput chemical screening
To catch a toxic metabolite Ten semifinalists are competing in an EPA challenge to incorporate metabolism into high-throughput chemical screening assays ▸ Lead researcher: Stéphane C. Corgié ▸ Affiliation: ZYMtronix
▸ Lead researcher: Hongbing Wang ▸ Affiliation: University of Maryland
Description of approach: Liver enzyme immobilization platform. Magnetic particles self-assemble, encapsulating and stabilizing liver enzymes. The immobilized metabolite-producing enzymes can be loaded onto multiwell plates suitable for toxicity screening.
Description of approach: Human primary liver cell co-culture model. Uses a multiwell cell culture platform that features plates with shallow plastic wells. The metabolite-producing liver cells are placed in the wells, which are then flipped over and inserted into microwell plates for toxicity screening.
▸ Lead researcher: James Rusling ▸ Affiliation: University of Connecticut
Description of approach: Magnetic beads are coated with liver enzymes. Enzyme-coated beads react with test chemicals in multiwell plates. Each resulting metabolite is transferred by vacuum filtration into a new multiwell plate for toxicity screening. ▸ Lead researcher: Brian Johnson ▸ Affiliation: Onexio Biosystems LLC
Description of approach: MICRO MT (Metabolism Integrated Cell RepOrter MicroTiter) multiwell plate. Uses human liver cell lines to generate chemical metabolites, which are routed via microchannels to neighboring wells where they are subject to standard toxicity screening. ▸ Lead researcher: Moo-Yeal Lee, Rayton Gerald ▸ Affiliation: Cleveland State University, Solidus Biosciences
Description of approach: Microarray bioprinting technology based on ink-jet printing. Human liver cell lines are printed in biomimetic hydrogels on multipillar plates, creating a 3-D cell culture that mimics the metabolite-producing qualities of the liver.
▸ Lead researcher: Lawrence Vernetti ▸ Affiliation: HanKayTox Consulting, University of Pittsburgh
Description of approach: Inexpensive, easy-to-use system for multiwell plates. Liver cells are encapsulated in gel and fixed on the end of a pin-plate lid, which can be inserted into a multiwell plate for in situ generation of metabolites. ▸ Lead researcher: Remco Westerink ▸ Affiliation: Institute for Risk Assessment Sciences, Utrecht
University Description of approach: Hepa-HTS test combines liver and nerve cells. Metabolites are produced using 3-D cultures of liver cells in a multiwell plate, then exposed to nerve cells in neighboring wells. ▸ Lead researcher: David Thompson ▸ Affiliation: MilliporeSigma
Description of approach: Uses a synthetic, self-replicating RNA vector that is capable of expressing multiple drug metabolism enzymes in the cell line of choice.
▸ Lead researcher: Albert Li ▸ Affiliation: In Vitro ADMET Laboratories LLC
▸ Lead researcher: Christopher Vulpe ▸ Affiliation: University of Florida
Description of approach: Exogenous xenobiotic metabolism system. As liver cells metabolize a test chemical, both the parent compound and its metabolites diffuse through a porous membrane to wells for toxicity screening in a cell type of interest.
Description of approach: Uses CRISPR-mediated gene targeting to turn metabolism on in cultured liver cells. Such CRISPR-modified cells are expected to mimic normal liver metabolism more accurately than standard liver cell lines.
to accelerate these efforts. Its ten semifinalists are now competing for five $100,000 awards, to be announced in December. Many of the semifinalists are developing approaches that rely on primary human hepatocytes, or liver cells, to metabolize a chemical that is under study. Metabolites are then transferred to a high-throughput assay. In two cases, however, researchers are making use of new gene-editing tools to put genes that encode for metabolic enzymes into cells. EPA scientists, meanwhile, are also developing solutions. “We want to retrofit and screen thousands and thousands of chemicals to determine whether or not metabolism changes the result,” Crofton says. The agency is facing the daunting task of prioritizing which of the tens of thousands of chemicals in U.S. commerce should be assessed for health risks. Changes Congress made in June to the U.S. law that governs commercial chemicals, the Toxic
Substances Control Act, set deadlines over the next few years for EPA to evaluate the safety of chemicals. EPA is also required to make decisions regarding the safety of new chemicals within 90 days. “If you have to rely on animal data, you won’t have it in time,” Crofton
ones interested in high-throughput chemical toxicity screening. Drug companies have long been interested in the bioactivity of metabolites formed when pharmaceuticals are converted in the liver. Such reactions have huge implications for drug-drug interactions and often change the bioactivity of
“We have a very diverse portfolio of bioassays. We’d like to be able to use a solution with as many of those assays as possible.” —Keith Houck, research toxicologist, Environmental Protection Agency says. “But if we have this huge battery of in vitro data that is available to help decision makers, they may be able to make a better decision. We are never going to have in vivo data for tens of thousands of chemicals,” he adds. Environmental regulators aren’t the only
a drug. The bioactivity of many anticancer drugs, for example, increases after metabolism in the liver. In many cases, drug companies are interested in learning which of the body’s metabolic pathways chemicals act through, Crofton says. In contrast, EPA is merely tryAUGUST 8, 2016 | CEN.ACS.ORG | C&EN
17
ing to determine whether a chemical’s bioactivity changes when it is metabolized. If the activity does change, EPA may want to go to the CH3O next step and try to identify the pathway and what enzymes are responsible, he notes. Many of the technologies being cultivated for EPA’s challenge are simultaneously undergoing development for pharmaceutical applications. Drug companies could benefit from approaches that consider metabolism in the early stages of drug discovery, when they screen large chemical libraries seeking lead molecules to treat various diseases. Without considering metabolism during such screening, pharma researchers are likely to miss many potential drug candidates, says Keith Houck, a research toxicologist with EPA. Large consumer product companies are also interested in how metabolism figures into the safety of chemicals in their products. Unilever, for example, has teamed up with EPA to determine if the company can use high-throughput in vitro approaches to evaluate the health risks of a few natural products found in some of its consumer products. Unilever has long been committed to reducing animal testing. Despite widespread recognition of
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compatible with these ToxCast assays, Houck says. “We have a very diverse portfolio of bioasOCH3 HO OH says. We’d like to be able to use a solution with as many of those Methoxychlor HPTE assays as possible.” the need to incorporate metabolism into The technologies being developed high-throughput cell-based chemical through the agency’s challenge use various screening assays, no system has been approaches to accomplish that goal. shown to reproduce the metabolic effects Several of the proposals use primary of the liver itself, Houck says. The goal of hepatocytes to mimic liver metabolism. In EPA’s challenge is to identify approaches such approaches, the small molecule of inthat are flexible enough to terest is allowed to diffuse work with many different into the liver cell where it is commercially available metabolized. The metabohigh-throughput assays. lite exits the liver cell and is EPA has a program called then placed in an existing ToxCast that aims to screen assay test system. thousands of chemicals for One semifinalist in the biological activity using challenge is planning to hundreds of high-throughgrow liver and brain tissue put assays. These assays are —Chris Vulpe, professor, on a single three-dimencommercially available and University of Florida sional culture plate. They come in a range of formats hope the system will allow and types, including both biochemical and them to assess the neural toxicity of both cell-based. The data are integrated with exthe parent compound and any of its liver isting in vivo animal data and structure-acmetabolites. tivity information to computationally preOther technologies in the challenge use dict the toxicity of chemicals. magnetic beads to capture the S9 fraction, It is critical that the tools being devela mixture of liver enzymes including cytooped in EPA’s metabolism challenge be chrome P450s. These enzymes metabolize
“Metabolism occurs in multiple places in the body.”
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Terrace Ballroom One • 10pm
FOR THE LOVE OF
CHEMISTRY 18
C&EN | CEN.ACS.ORG | AUGUST 8, 2016
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drugs and other chemicals the body is exposed to. Internally, EPA is developing a method to encapsulate the S9 fraction of metabolic liver enzymes using a polysaccharide called alginate. The alginate S9 mixture forms gel-like microspheres that are attached to the tips of prongs on a lid that fits over a standard multiwell plate. “It is like having little pieces of liver on the end of these tips. You stick them down into each well,” Crofton explains. “When you put the chemical in the well, the chemical gets metabolized by the S9 fraction, and the metabolite comes out.” EPA scientists and a couple of semifinalists are also working on ways to make cultured liver cells act more like liver tissue. “Some of these cells have more metabolizing capability than others,” says Crofton. Using gene insertion techniques, “we can make the cells express more metabolizing enzymes.” “The fundamental problem with current in vitro toxicity testing is that you are using these immortalized cell lines,” says semifinalist Chris Vulpe, a professor at the University of Florida. The trick, he says, is making the cells express enzymes in the amounts normally found in the liver. Using a modified version of the CRISPR gene-editing technique, Vulpe’s team is working to turn on and activate transcription of DNA that encodes cytochrome P450 enzymes. Eventually he hopes to move beyond liver to other tissues, including intestinal, kidney, and breast tissues. “Metabolism occurs in multiple places in the body,” Vulpe says. Whether EPA’s challenge will ultimately lead to a reduction in animal testing remains to be seen. But some experts predict that such technologies could be used by pharmaceutical companies to help weed out toxic drug candidates before they are tested in animals. “It will probably help in reducing animal models,” says Randy McClelland, chief executive officer of SciKon Innovation, a North Carolina-based company developing fluid culture systems with integrated channels. Although the company is not one of the semifinalists in EPA’s challenge, it is working with some of the semifinalists to develop solutions for the next stage of the competition. Rusty Thomas, director of EPA’s National Center for Computational Toxicology, says he is impressed with the creativity and innovation of the proposals submitted for the challenge. “The next stage is going to be important for demonstrating whether those innovative ideas can be put into practice,” he says. EPA expects the challenge to enter its final stage in early 2017. ◾
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ENTREPRENEURSHIP
Year founded
Measuring a serial entrepreneur’s success
Company name Technology focus Estimated venture and private equity funding Major milestones Current status (2015 figures)
By any yardstick, Robert Langer’s creation of 31 start-ups is a testament to his technical and business acumen
1988 ANN M. THAYER, C&EN HOUSTON
Neomorphics Biocompatible materials $6 million Acquired by Advanced Tissue Sciences for $21 million in 1992. Bankrupt in 2002. Technology acquired by Smith & Nephew and in use at regenerative medicine firm Organogenesis.
B
CRE DIT: YANG H. KU/C&EN
ind Therapeutics, a 10-year-old nanomedicine firm, declared bankruptcy in May and last month agreed to sell its assets to Pfizer. Although collaborations with leading drug companies had helped Bind move candidates into the clinic, it achieved mixed results there. Toward the end, it was trying to restructure its finances, refocus its R&D, and partner its lead candidate. Although such downturns are common in the drug R&D world, this one was a rare setback for a firm based on technology from the lab of chemical engineer Robert Langer at Massachusetts Institute of Technology. By the time Bind was founded in 2006, Langer had already helped create at least 20 companies, generally in the areas of medical devices, drug delivery and development, and tissue and cell engineering. Although there are other notable scientist-entrepreneurs, such as the Institute for Systems Biology’s Leroy Hood and Harvard University’s Gregory Verdine, it is likely that Langer’s record as an inventor and company creator is unsurpassed in the chemistry, engineering, and materials science worlds. The proof is in the pudding. Over three decades, Langer has helped found about 30 companies that have raised an estimated $2 billion in venture capital and private equity funding to date. A large chunk of that—$650 million—went to the mRNA drug company Moderna Therapeutics. And although it’s still early in the life of many Langer companies, they are clearly amassing a remarkable record of accomplishment. In the start-up world, accomplishment can be measured many ways. Investors generally want to see companies get acquired or hold an initial public offering (IPO) of stock. Barring those two options, a company is expected to turn a profit or shut down. Among companies connected to Langer, nine have become publicly traded, raising more than $300 million combined through IPOs—and more through follow-on offerings. Recently, Selecta Biosciences managed to raise a respectable $70 million despite a challenging period for IPOs.
1987
1987
Enzytech Microsphere drug delivery $10 million to $20 million Acquired by Alkermes in 1993 stock deal. Technology in use.
On par with other venture-backed startups, 10 of his companies were acquired and three merged with other firms. The deals were worth as much as $230 million. At least four Langer-connected companies have themselves created new start-ups. On average, according to the National Venture Capital Association, about 200 biotech and medical device firms receive initial venture capital funding in a given year. That Langer has been able to start up at least one company, if not two or three, in any year is a tribute both to the productivity of his lab and the value that investors assign to his work. The venture capital firm Polaris Partners has invested in at least 20 of Langer’s companies, spending more than $220 million. Noteworthy is that just a handful of Langer’s companies have gone bankrupt or shut down, a record that far exceeds expectations for venture-capital-backed firms. Among biopharma and medical device startups, “more companies fail than succeed,” often within a few years, according to NVCA. It’s also a major accomplishment that the
Opta Food Ingredients Microspheres for food applications $10 million to $20 million IPO in 1992. Acquired in 2002 for $28 million; now part of SunOpta. Technology in use.
science originating at MIT continues to be employed, even if the company based on it has ceased to operate. For example, Juniper Pharmaceuticals is testing products that use technology acquired from the now-defunct Combinent BioMedical Systems. And companies that bought the early start-ups still find value in the acquired technology. Of the original Langer firms still operating, most have products in clinical testing. Some of the more recently founded ones are already developing lead product candidates. Many of the companies have partnered with major firms. And a few—including Living Proof, Momenta Pharmaceuticals, and T2 Biosystems—have brought products to the market and are generating revenues. As a result, it appears that Langer has notched another accomplishment, one that has nothing to do with making money. He started his first company, he wrote in a 2013 Nature Biotechnology article (DOI: 10.1038/ nbt.2609), “because I realized it was an effective path for transforming science into life-saving and life-improving inventions.” AUGUST 8, 2016 | CEN.ACS.ORG | C&EN
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1998 1997
Path of ingenuity Langer’s entrepreneurial journey has led to more than 30 start-ups over 30 years.
1992
Focal Biodegradable materials for surgery $59 million $25 million IPO in 1997. Acquired in 2001 by Genzyme for total of $25 million. Technology in use.
2006 Bind Therapeutics Nanoparticle-based therapeutics $73 million $71 million IPO in 2013. Bankrupt, assets to be sold for $40 million. Two candidates in clinical testing.
Reprogenesis Tissue growth scaffolds $17 million Merged in 2000 with Creative BioMolecules and Ontogeny to form Curis. Related programs largely suspended in 2002.
Advanced Inhalation Research Pulmonary drug delivery $2 million Acquired by Alkermes for $114 million in 1999. Technology part of 2011 spin-off Civitas Therapeutics. Civitas acquired by inhaled drug developer Acorda Therapeutics in 2014.
1993
1993
Acusphere Microsphere imaging agents $95 million $53 million IPO in 2003. Later delisted. Failed to get product approved. No longer operating.
EnzyMed Combinatorial biocatalysis for drug R&D na Acquired by Albany Molecular Research Inc. in 1999 for $21 million. Technology may be in use.
2006
2006
2005
Semprus BioSciences Medical device coatings $26 million Completed Series B funding. Acquired by Teleflex in 2012 for $30 million up front. Issues encountered developing technology, but Teleflex expects to file for approval in catheter application.
T2 Biosystems Nanoparticle diagnostics, instruments $93 million $60 million IPO in 2014. Two products launched. $2.8 million in revenues, net loss.
InVivo Therapeutics Scaffolds for spinal cord therapy $11 million One funding round. Became public in 2010. Product in clinical testing. No revenues, net loss.
2007
2011
Selecta Biosciences Targeted nanoparticles $152 million Completed Series E funding. $70 million IPO in June 2016. One clinical and two preclinical candidates.
XTuit Pharmaceuticals Microenvironment-activated drugs $26 million Private. Completed Series A funding. Developing lead candidates.
2008
2008
2009
2011
Seventh Sense Biosystems Microneedle blood collection $33 million Private. Completed Series B funding. Soon to file for marketing authorization in the U.S. and Europe.
Taris Biomedical Urological drug delivery $52 million Private. Sold lead clinical-stage asset to Allergan in 2014 for up to $588 million. Relaunched late 2015 with $32 million investment. Bladder cancer agent in clinical testing.
Kala Pharmaceuticals Mucosal drug delivery $114 million Private. Completed Series C funding. One ophthalmic candidate in clinical testing for three conditions.
480 Biomedical Bioresorbable materials for drug delivery $45 million Spin-out of Arsenal Medical. Completed Series C funding. Scaffold to treat vascular disease/injury in clinical testing.
22
C&EN | CEN.ACS.ORG | AUGUST 8, 2016
1998
1999
1999
2000
Sontra Medical Transdermal drug delivery $18 million Merged with Echo Therapeutics in 2007. Technology licensed to Ferndale Pharma Group. Glucose monitoring system in development. Echo’s stock delisted in July 2016.
TransForm Pharmaceuticals Polymorph crystallization $45 million Acquired by Johnson & Johnson in 2005 for $230 million. Technology in use.
Microchips Biotech Silicon-based drug delivery $58 million Private. Four funding rounds. Equity investment by Teva Pharmaceutical Industries in 2015. In clinical development partnerships.
Combinent BioMedical Systems Transvaginal drug delivery $5 million Four funding rounds. No longer operating. Technology acquired by Juniper Pharmaceuticals and now in clinical testing.
2001
“Because I realized it was an effective path for transforming science into lifesaving and life-improving inventions.” —Robert Langer of MIT on why he started his first company (Nat. Biotechnol. 2013, DOI: 10.1038/nbt.2609)
Momenta Pharmaceuticals Complex-sugar-based drugs $40 million $35 million IPO in 2004. Two products approved. Three in clinical testing. $90 million in revenues, net loss.
2005
2004
2004
2003
Arsenal Medical Nanofiber drug delivery $47 million Private. Four funding rounds. Spun out 480 Biomedical in 2011. Developing polymer foams and fiber for tissue therapy and repair.
Living Proof Hair and skin care products $53 million Private. Completed Series C funding. Selling products since 2009. Profitable.
Pervasis Therapeutics Therapies for vascular healing $40 million Completed Series C funding. Acquired by Shire for up to $200 million in 2012. Development of Vascugel halted in 2014 afer Phase II.
Pulmatrix Inhaled therapeutics $48 million Three funding rounds. Merged with Ruthigen in 2015 and went public. Three products in clinical trials. $1.1 million in revenues, net loss.
2011
2012
Moderna Therapeutics Modified mRNA delivery $650 million Private. Four funding rounds. Created four therapy-focused companies. Partnerships with big pharma and nonprofit organizations for clinical development.
Blend Therapeutics Biologic drug conjugates $84 million Private. Completed Series C funding. Now Tarveda Therapeutics. Spun off platinum cancer drug firm Placon Therapeutics in January 2016.
na = not readily available. Sources: Company information, SEC filings, Crunchbase, Informa Strategic Transactions, CB Insights
Year founded Company name Technology focus Estimated venture and private equity funding Major milestones Current status (2015 figures)
2013
2015
SQZ Biotech Cell therapy engineering $6 million Private. Completed Series A funding. Signed Roche partnership worth up to $500 million.
Olivo Labs Dermatological biomaterials Seed funding Materials based on technology developed at Living Proof. Start-up phase with materials in in vivo testing.
SUSTAINABILITY
Unsustainably mined rare earths from China play major role in wind turbines and hybrid cars JEAN-FRANÇOIS TREMBLAY, C&EN HONG KONG
L
ast month, Honda announced that it has developed the world’s first hybrid electric car free of most rare-earth metals. For Honda, the new car helps resolve one of the great contradictions plaguing the clean technology sector: Fossil-fuel-saving products such as wind turbines and hybrid car engines often depend on rare earths sourced from China at great environmental cost. A report just published by the Hong Kong-based environmental group China Water Risk (CWR) puts the spotlight on the hidden cost of rare-earth consumption by the cleantech industry. Despite knowledge of these costs, the report says, manufacturers have yet to make an effort to avoid rare earths produced at unsustainable Chinese mines. “The world is seeking cleaner devices that consume less energy, and this will likely result in increased demand for rare earths,” says Debra Tan, director of CWR. “Corporates using rare earths should ensure that they are sourced legally and sustainably in China.” Rare earths are a family of 17 elements used in many industries. According to CWR’s research, building 1 MW of wind energy capacity requires 171 kg of rare earths. In addition, rare-earth magnets play a key role in hard disk drives, headphones, and the motors of electric cars and cordless tools. Many smartphones incorporate lanthanum, cerium, praseodymium, and neodymium. Honda, which has eliminated dysprosium and terbium from its hybrid vehicle motors, continues to use neodymium. China is the world’s dominant producer of rare earths. Although the country is home to only about a quarter of the world’s reserves of the materials, it accounts for roughly 85% of supply. China achieved its dominance of the industry by not truly accounting for the environmental cost of rare-earth production, CWR contends.
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C&EN | CEN.ACS.ORG | AUGUST 8, 2016
Cleaning up the damage already caused by the rare-earth industry in Ganzhou, a city in the province of Jiangxi that bills itself as the “kingdom of rare earths,” would cost an estimated $5.5 billion. But according to CWR, the rare-earth industry in Ganzhou generated profits of less than $1 billion in 2014. Meanwhile, in Baotou in Inner Mongolia, a city that calls itself the “capital of rare earths,” “environmental monitoring authorities have reported contamination and radiation in groundwater, grassland, and livestock” around the giant ponds where mining waste is stored, says Hongqiao Liu, the lead author and researcher of the CWR report. A high incidence of cancer has been observed in nearby communities, she adds, although it’s not been linked to rare-earth mining activities. What cannot go on forever will eventually stop, and China is making some headway in controlling the excesses of the rare-earth industry. In recent years, rare-earth companies have been consolidated into six state-owned
Valuable heavy rareearth oxides are recovered through a series of processes in acidic open-pit leaching ponds in the hills of Ganzhou. This semifinished product is sold to separators for further processing.
firms accounting for nearly all of China’s official production. The companies are coming under increasing regulatory scrutiny. For instance, in June this year, China introduced its first-ever soil pollution law. In 2014, Chinese authorities formulated their first set of technical specifications for in situ leach mining processes. First introduced in 1996 in Ganzhou mines, in situ leaching involves the injection of liquid-containing displacer chemicals, which separate rare-earth ions from the ores into wells running perpendicular to mines. This allows the rare-earth ores to flow into ponds, CWR explains. But such measures won’t help much, according to CWR, unless they also tackle the damage caused by wildcat rare-earth mining operations that don’t implement any form of environmental control or remediation. Production by illegal miners appears to be substantial, CWR says, amounting to as much as twice the official production figures for southern China. Illegally produced rare earths are subject to easily skirted controls within China, and nothing prevents international companies from buying them. CWR argues that China cannot shut down illegal miners without international cooperation. In 2010, a Chinese crackdown on illegal producers closed some mines but left others untouched. International buyers of rare earths could pledge to buy only materials sourced from sustainable mining operations. Precedents exist for such voluntary commitments, CWR’s Tan says. In the palm oil industry, she notes, almost all major international buyers now exclusively source from sustainable plantations. But environmental controls will come at a cost. In 2010, major buyers of rare earths got up in arms when prices skyrocketed after China imposed export quotas that it said were motivated by environmental concerns. The quotas were removed in 2015 after the World Trade Organization ruled them unjustified. Rare-earth prices may well start to climb again if suppliers of clean technologies decide to resolve the contradiction of their reliance on a dirty raw material. Even Honda will need to brace itself for that. ◾
CRE DIT: HONGQIAO LIU
How rare earths bring clean technologies, dirty landscapes
BIOTECHNOLOGY
Athletes at Rio Olympics face sophisticated doping tests Officials can now check for long-ago anabolic steroid use, with gene doping tests on the horizon SARAH EVERTS, C&EN BERLIN
A
thletes currently attending the Summer Olympics in Rio de Janeiro may eventuTurkish weight lifter Sibel ally face a new kind of doping test: one Özkan was recently stripped that checks whether they have received of the silver medal she won performance-enhancing gene therapy. According to at the 2008 Beijing Olympic the International Olympic Committee’s medical and Games after retesting scientific director, Richard Budgett, samples collected showed that she had doped. in Rio will be tested for gene doping at some point after the games, even though the test won’t be run during the Olympics itself. It’s up for debate whether WADA doping Officials want to know whether athletes have been labs will eventually find any athletes guilty When scientists retested given synthetic DNA that codes for erythropoietin of gene doping at the Rio Olympics this athletes’ samples in 2016 (EPO), a hormone that increases red blood cell producmonth. There is no evidence that Olympic with more sensitive methods, tion and, consequently, athletic performance, said Carl athletes are currently undergoing gene they found a higher rate of Johan Sundberg, an exercise physiologist at Karolinska doping, Sundberg said. But then again, “the doping than initially reported. Institute and member of the World Anti-Doping Agentest has never been used before,” he added. cy’s gene doping panel. Sundberg explained the techEven so, evidence does exist that at least % of samples that tested positive nique that Olympic officials plan to use to test for gene one corrupt German coach tried to orgaBeijing 2008 doping at the EuroScience Open Forum (ESOF) confernize gene doping for his athletes more than ence, held July 23–27 in Manchester, England. a decade ago: In a 2006 trial, prosecutors Retroactive testing isn’t good news for corrupt athexhibited e-mails written by former Ger0.52 letes. When scientists retested fluid samples from athman Athletics Association coach Thomas 7.14 letes competing at previous Olympics Games, namely Springstein in which he requested EPO Beijing’s 2008 and London’s 2012 Summer Games, gene doping products from his drug dealer. many more athletes tested positive for Although only a handful of gene banned substances than with prior analyses. therapy procedures to treat disease Tested at time Retested The tests, carried out with improved analythave been approved by worldwide of Olympics in 2016 London 2012 ical techniques, revealed that, on average, regulators, WADA started considering 8% of the athletes at those two games actually tested the possibility that athletes might abuse positive for banned substances, up from an average of gene doping in 2002, and in 2003 it added 0.18 less than 1% observed in past games. The increase is gene doping to its list of prohibited sub9.43 “sensational,” said Arne Ljungqvist, a 1952 high-jump stances and methods. Olympic athlete and former vice president of the World The gene doping test is based on work Anti-Doping Agency (WADA), at the ESOF session. by Anna Baoutina and colleagues at the Add these data to other recent doping scandals, National Measurement Institute in Sydand the International Olympic Committee has had ney, Australia. The technique relies on the Note: Not all samples originally tested its hands full lately. Last month IOC announced that gene that naturally codes for EPO in the during the Olympics were retested in 2016. For example, there were 5,051 Russian athletes could participate in the Rio Games, human body and the fact that it contains despite evidence of sample tampering at the 2014 Sochi samples tested in 2012 in London. In four introns, sequences that get cut out of 2016, 403 of those were retested. Winter Olympics and indications of an entrenched messenger RNA after the gene has been Sources: World Anti-Doping Agency and doping culture in the country’s athletic community. Arne Ljungqvist transcribed. Synthetic EPO DNA inserted
CRE DIT: NEWSCOM
Busted
AUGUST 8, 2016 | CEN.ACS.ORG | C&EN
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during gene therapy is unlikely to have such intron sequences. Gene dopers could be caught if officials scanned blood samples for EPO DNA without these introns. This is not the only strategy proposed for checking athletes for gene doping. Researchers have also designed tests that search for proteins in blood that are unique to the viruses scientists use to transport genes across a cell membrane and then into a genome (Drug Test. Analysis 2012, DOI: 10.1002/ dta.1347). Other techniques rely on looking at the sugars decorating the protein that’s been produced from the contraband: For example, EPO is normally produced in the kidney, where it is glycosylated in four different places. Gene dopers, however, are more likely to inject EPO DNA into muscle, which has different glycosylation pathways. Unusual sugar decorations could act as a smoking gun for gene doping, Sundberg said. In fact, doping labs currently do an analogous test that looks for athletes who have injected bacteria-synthesized EPO directly into their blood, he added. Bacteria decorate EPO differently than humans do, giving testers a way to catch cheaters. WADA is also funding research to test whether athletes have received gene therapy for growth factor proteins, such as growth hormone and IGF-1, which bolster muscle development. The doping research field is also investigating ways to test for anticipated cell doping in athletes, Sundberg said. Doctors have for a long time transplanted bone marrow stem cells in cancer patients, he said. “In the future, athletes may transplant
cells to improve heart and muscle strength and endurance.” And with the advent of the CRISPR/Cas9 technique, athletes could start paying for genetic editing of their own cells. “You might think it sounds like a bit of science fiction, but it might quite soon not really be so,” Sundberg said. Although researchers are trying to anticipate future doping strategies, steroids are currently still the number one choice for corrupt athletes, Ljungqvist said at ESOF. The spike in positive doping results that scientists saw when they retested samples from Beijing and London, for instance, can be attributed to steroids. Researchers have made improvements in analytical instruments— primarily mass spectrometers—for detecting contraband compounds, and they’ve discovered so-called long-term metabolites of banned anabolic steroids, including metandienone, oxymetholone, and stanozolol, in athletes’ urine. In the past, researchers could only detect metabolites of a banned steroid in urine for weeks after the last dose, Ljungqvist explained. “Now that window has been expanded to a couple of months” with the identification of these metabolites that stick around much longer. After a WADA-accredited laboratory in Cologne, Germany, started testing for longterm metabolites of metandienone, the lab saw a 400% increase in positive doping results (Br. J. Sports Med. 2014, DOI: 10.1136/ bjsports-2014-093526). Though most media attention focuses
There’s also a growing doping problem among the general public.
on doping by professional athletes, there’s also a growing doping problem among the general public, Ljungqvist said. “Nine-tenths of the iceberg underwater is the doping taking place in recreational sports or by people trying to enhance their body image in entirely unregulated ways,” said doping researcher Mike McNamee from Swansea University to the ESOF delegates. “It’s not just young men wanting to look like their favorite Hollywood actor. It’s also policemen, firefighters, security personnel, and bouncers,” he said. Although everyone working in doping agrees it’s a huge problem among the general public, there’s no reliable prevalence data, McNamee said. Because it’s not possible to test the general public for contraband drugs—except in Denmark, where doping officials are allowed to test people in public gyms—education is probably the best way to reduce the use of contraband drugs by the general public, McNamee added. Of course, it’s hard to convince the general public not to use contraband substances if professional athletes caught doping don’t suffer consequences. “I am one of those who was fooled in Sochi by the Russians,” Ljungqvist told reporters during a press conference at ESOF. “At night, behind my back, [they] were changing samples through a hole in the wall. This is not the first time I was cheated by the Russians. During the Beijing Games, we discovered that female athletes’ urine was exchanged. This deserves some punishment.” When asked about IOC’s recent decision not to ban Russian athletes from participation in Rio, Ljungqvist replied: “In the IOC report, I would have welcomed an explanation about why this penalty wasn’t chosen.” ◾
C&EN TALKS WITH ANDY BRUNNING Meet the mastermind behind C&EN’s Periodic Graphics and the blog Compound Interest at the ACS National Meeting.
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Tuesday, August 23 11:00 AM – 12:00 PM Pennsylvania Convention Center ACS Booth Theater; Booth #827A
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Cover story
In brief With their unmatched ability to generate intense beams of radiation ranging from radio waves to X-rays, synchrotrons are indispensable tools for modern materials analysis. Worldwide, nearly 60 synchrotrons are running or nearing completion, with new ones being planned. Scientists working in fields such as energy storage, paleontology, catalysis, biology, and electronics are harnessing these facilities to study the microscopic structure, chemical composition, and other properties of their materials of choice.
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Revealing materials’ secrets with synchrotron light With the ability to probe a wide range of materials, these powerful light sources are attracting researchers, from paleontologists to catalyst chemists
CRE DIT: EUROPEAN SYNCHROTRON RADIATION FACILITY (ENGINE ERS); ARGONNE NATIONAL LABORATORY (AERIAL)
MITCH JACOBY, C&EN CHICAGO
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lexander Moewes is a high-energy physicist. Literally. The University of Saskatchewan researcher doesn’t smash atoms together to study subatomic particles— the typical work of “real” high-energy physicists. Rather, Moewes radiates energy and enthusiasm when he talks about his favorite research tools—synchrotrons. “With synchrotron radiation, you can do experiments in so many areas of science that just cannot be done in any other way,” he says excitedly. These stadium-sized, multi-million-dollar research facilities enable scientists to reveal the structure, chemical composition, electronic properties, and other features of specimens critical to
materials science, chemistry, archaeology, molecular electronics, and a host of other disciplines. For that reason, countries around the globe have built—or are in the process of building or upgrading—about 60 synchrotrons. Most of these facilities are in Europe, North America, and Asia. But the SESAME (Synchrotron-light for Ex-
An aerial view of Argonne National Laboratory’s Advanced Photon Source near Chicago. Shown opposite is the inside of the European Synchrotron Radiation Facility in Grenoble, France.
AUGUST 8, 2016 | CEN.ACS.ORG | C&EN
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perimental Science & Applications in the All of these unique capabilities of synBy using a powerful synchrotron imMiddle East) synchrotron near Amman, chrotron radiation offer unprecedented aging method to scrutinize the hidden Jordan, the first such facility in the Middle ways of peering deep into the interior of embryonic skeletons preserved in the East, is scheduled to be up and running by catalysts, battery materials, ancient artieggs, the team now knows the egg layer’s next year (see page 31). And last Novemfacts, and other specimens without having true identity—an anguimorph lizard, a ber, an international team of scientists to first isolate them from their natural or category that includes Komodo dragons took the first steps to establishing a syntechnologically relevant environments. (PLOS One 2015, DOI: 10.1371/journal. chrotron center in Africa, the only habitThe wide applicability of synchrotron pone.0128610). able continent without such a facility. methods and the opportunity to use them According to team leader Vincent Synchrotrons produce intense rato discover new phenomena continues Fernandez, a beamline scientist at the diation, ranging from radio waves to to excite Moewes nearly 30 years after he European Synchrotron Radiation Facilhigh-energy X-rays, by accelerating elecfirst began working at these facilities. ity, in Grenoble, France, the embryonic trons to nearly the speed of light and drivSome adrenaline junkies get their thrills lizard skeletons are the oldest ones ever ing them through a circular storage ring by jumping out of airplanes or scaling discovered in fossil eggs. Most lizards lay lined with powerful magnets. Mount Everest, he says. Moewes gets his fix so-called soft-shelled eggs, says FernanResearchers working at experimental by exploring uncharted scientific territory dez, who was trained as a paleontologist. stations, or beamlines, which are located at the world’s most powerful light sources. So the discovery that the eggs, which were along the ring’s perimeter, use various the hard-shelled type, held anguimorph types of optics to tune in precisely to the embryos “came as a surprise and alters our exact wavelength range needed for their understanding of the evolution of lizard studies. The high degree of tunability, esreproduction,” he says. pecially in the X-ray range, is one of the key In 2003, paleontologists discovered centiSynchrotron radiation was crucial to features of synchrotrons that isn’t available meter-long fossilized eggs in northeastern the discovery. During the initial examwith other light sources, explains Moewes, Thailand that turned out to be 125 million ination of the fossils, the team observed who, together with his group, conducts reyears old. Originally, the scientists conminute embryonic bones poking out of the search at the Canadian Light Source, in Sas- cluded that a small theropod dinosaur or rocky material in some of the eggs. The katoon, Saskatchewan, and the Advanced perhaps a primitive bird laid the tiny eggs. fragile bones held critical clues about the Light Source, in Berkeley, Calif. species’ identity, but they were That capability of synchroA synchrotron-based X-ray tomography technique revealed encased in rock, which prevented trons, Moewes explains, not only hundreds of tiny embryo bones buried inside a 1-cm-long, their extraction and presented enables researchers to selectively 125 million-year-old lizard egg. another formidable analytical probe each element in a sample challenge. individually, but also allows them “The problem often in paleto zoom in on the orbital of interontology is that fossil bones and est, distinguish among valencies the surrounding rock have similar and oxidation states, and deterdensities,” thwarting the chance mine an atom’s bonding geomeof identifying them via common try and coordination. nondestructive imaging methods, Anthony W. Van Buuren, a Fernandez says. materials science research group Ultimately, the team solved leader at Lawrence Livermore the puzzle by using a synchroNational Laboratory, points to tron X-ray technique known as another unmatched synchrotron phase-contrast microtomogfeature—exceptional brilliance raphy, which is particularly or beam intensity. The large numsensitive to minute differences ber of X-ray photons emitted in in the densities of a sample’s fleeting bursts of synchrotron components. light enables researchers to make Synchrotron X-ray methods ultrafast time-dependent meaare also revealing secrets hidsurements, an ideal way to capture ing inside other types of fragile nanosecond snapshots of proteins ancient artifacts. For example, and other molecules undergoing a recent study revealed the handrapid changes. written text concealed inside With recent progress in conrolled-up papyrus scrolls that trolling synchrotron radiation, were charred when Mount Vesuscientists can now also work with vius erupted nearly 2,000 years very fine beams of X-rays. This ago. gives researchers a high degree of Another investigation despatial control over their expertermined that the secret to iments, opening the door to new the strength of some Roman types of microscopy that provide architectural structures is the nanoscale structural information formation of platelike crystals along with detailed chemical of strätlingite, a durable calcium maps. aluminosilicate mineral that
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CRE DIT: MICROSC . MICROANAL.
Peering into fossils and ancient artifacts
CRE DIT: SESAME
Photons for peace In November 1995, Eliezer Rabinovici sat in a large Bedouin tent on the southeast coast of the Sinai Peninsula contemplating the chances for scientific cooperation between Israeli and Arab scientists. The Israeli physics professor from Hebrew University of Jerusalem, together with Egypt’s minister of higher education and more than 100 Egyptian, Moroccan, Jordanian, Israeli, and Palestinian scientists, had gathered in the Egyptian town of Dahab, hoping against hope to establish a lasting framework for an international center of scientific excellence in the Middle East. As if on cue from the director of an epic biblical film, the ground began reverberating and Mount Sinai started shaking, Rabinovici recalls. A magnitude-6.9 earthquake rumbled through the region. None of the meeting attendees was hurt. “We took it as a clear sign from above that something was going on,” he says. “Hopefully, something good.” Indeed, it was good. Twenty-one years later, thanks to the perseverance and dedication of scientists from countries that are often at odds with one another, the first synchrotron light source in the Middle East stands nearly ready to open its doors to scientists. At the end of July, officials at the facility called for research proposals. Located near Jordan’s capital, Amman, the research center, which is known as Synchrotron-light for Experimental Science & Applications in the Middle East, or SESAME, follows the organizational structure of the European Organization for Nuclear Research, or CERN, Europe’s multinational nuclear research center. SESAME’s current members are Bahrain, Cyprus, Egypt, Iran, Israel, Jordan, Pakistan, the Palestinian Authority, and Turkey. In February, engineers began installing the cells that make up SESAME’s electron storage ring. According to Mohamed Yasser Khalil, SESAME’s administrative director, installation and testing of the storage ring and associated equipment should be completed before the end of the year. Two beamlines, out of a total of roughly 25, are also nearing completion and expected to be up and running by spring 2017. Even before researchers begin traveling to Amman to use SESAME’s powerful radiation to reveal secrets about the structure and chemical composition of
their samples, Rabinovici considers the 20-year collaboration among Middle Eastern scientists to be a success in its own right. “Just consider how much turmoil has gone on in the region during that time,” says Rabinovici, who just completed a term as vice president of SESAME’s council. Because synchrotrons are used by such a wide range of researchers, including materials scientists, chemists, biologists, archaeologists, and others, the existence of a state-of-the-art light
SESAME can also benefit the region by spurring development of engineering firms and high-tech companies to manufacture power supplies, cooling equipment, and other infrastructure components needed for experiments at the facility. One of the most important goals of the new facility, according to Sayers, is to conduct first-class science. An excellent reputation will motivate top-level scientists to work there. And with those scientists come younger
Construction of the SESAME synchrotron facility near Amman, Jordan, is almost complete. source in the Middle East should help “reverse the brain drain from the region,” says Zehra Sayers, chair of SESAME’s scientific advisory committee. Sayers, who is a professor of engineering and natural sciences at Sabanci University, in Istanbul, Turkey, explains that many Middle Eastern scientists who wanted access to synchrotrons chose to accept synchrotron staff positions and academic appointments abroad. “SESAME offers an opportunity for them to come back,” she says. It also provides an incentive to young scientists to stay put in the Middle East. A large-scale laboratory such as
ones, Sayers says, who are energetic and social and often stay up all night running experiments. “Through the language of science, especially at two o’clock in the morning, these young people from all over the Middle East will get to know each other and learn to trust one another,” Sayers stresses. “That kind of trust leads to collaborations and lasting relationships.” “As scientists with a natural tendency to collaborate, we owe it to our society to try to build a bridge to understanding,” Rabinovici says. “Will we succeed or fail? Time will tell. But it’s our responsibility to do our utmost.” AUGUST 8, 2016 | CEN.ACS.ORG | C&EN
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prevents cracks from propagating through ancient buildings’ mortar.
Analyzing new types of electronics For decades, the electronics industry has produced one generation after another of ever-faster and more powerful electronic devices by shrinking their silicon-based components. Physical limitations have begun impeding that trend, driving scientists to look for alternative ways to squeeze more electronics into smaller spaces. Some engineers want to turn to molecular electronics, a system in which individual molecules serve as circuit components.
semiconducting and magnetic. But the basis of its magnetism is poorly understood, which hampers efforts to design even better spintronic materials. On the basis of X-ray absorption and X-ray scattering methods, the team found that the magnetism is linked to the 3d orbital energies of iron atoms, specifically in the Fe3+ state, that reside in indium lattice sites directly adjacent to a vacancy created by a missing oxygen atom (Phys. Rev. Lett. 2015, DOI: 10.1103/physrevlett.115.167401). That level of detail could only have been uncovered in a synchrotron experiment, Moewes points out. Meanwhile, Benjamin Stadtmüller and Christian Kumpf of the Jülich Research Center and coworkers
ies focused on a silver-supported film of perylene tetracarboxylic dianhydride (PTCDA) and copper(II) phthalocyanine (CuPc). When they compared the mixed-molecule film to those with just a single component, the group found that the PTCDA-silver bond elongated, suggesting it became weaker, and the CuPc-silver bond contracted, suggesting it became stronger. But analysis of the orbital energies showed the opposite was true: The bonds that elongated had become stronger, and those that shrunk became weaker. Using a standing-wave X-ray technique and quantum calculations, the researchers determined that the bond length adjustments brought PTCDA and CuPc to nearly equal heights above the surface. That change caused CuPc to become a better electron donor and PTCDA a better acceptor, which improved charge transfer through the system—a key feature required of molecular electronic devices (Nat. Commun. 2014, DOI: 10.1038/ ncomms4685).
Synchrotron-based studies show that on a silver surface, PTCDA (red) and CuPc (blue) adjust their bond lengths and energies to enhance the system’s charge-transfer properties. Others are investigating spintronics, in used a synchrotron X-ray technique to sort which digital information is controlled by out some counterintuitive findings on a electron charge—as is done today—and molecular electronics system. The team electron spin, which is associated with explores the charge-transfer interplay that magnetism. Implementing those strateoccurs at interfaces between metal surfacgies requires understanding atomic-scale es and organic molecules. details of the underlying materials. SynIn some of these systems, for example chrotron-based analytical methods have in optoelectronic devices, the molehelped those studies. cules absorb light and transfer electrons At the Canadian Light Source, in Sasthrough neighboring molecules to a metal katoon, Saskatchewan, for example, a electrode. In other systems, the molecules research team led by Univermodify electric current for sity of Saskatchewan physiselect applications. In all of cist Alexander Moewes has these cases, the molecules’ been studying iron-doped To see how bonding details strongindium oxide. The material synchrotrons generate ly affect their electronic is a promising candidate light, check out cenm.ag/ properties. for spintronics because it is howasynchrotronworks. The Jülich team’s stud-
Video Online
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Many of today’s large-scale chemical processes, such as petrochemistry, pollution scrubbing, and chemical synthesis, depend on solid catalysts. High temperatures, high pressures, and other harsh working conditions eventually cause these catalysts to fail, which causes downtime and raises costs. Synchrotron methods are providing researchers with clues about catalyst failure mechanisms and strategies for avoiding them. In one such study, a team led by Bert M. Weckhuysen of Utrecht University used an X-ray nanotomography method to examine a series of fresh and used fluid catalytic cracking catalysts. Oil refiners use such catalysts to produce gasoline and other products from crude oil. The catalysts typically consist of two active components held together by a binder: a zeolite with roughly 1-nm-wide pores and a clay with larger pores. The team found that the catalysts fail because iron and nickel impurities from crude oil accumulate at the entrances to the clay’s large pores. That process prevents crude oil molecules from reaching the zeolites’ catalytic sites, which are located in narrow channels in the interior (Sci. Adv. 2015, DOI: 10.1126/sciadv.1400199). Weckhuysen suggests that catalyst lifetimes might be extended by coating the catalysts with a clog-resistant macroporous layer. To sort out the details of the pore-clogging process, the Utrecht team again
CRE DIT: JÜLICH RESEARCH CE NTE R AND UNIVERSITY OF GRAZ
Improving solid catalysts
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CRE DIT: ARGONNE NATIONAL LABORATORY
Tell a friend why you love chemistry. turned to a synchrotron Argonne physicists Jörg high-energy (>50 keV) method. This time they Maser (left) and Robert X-rays to peer deep inside generated visual evidence Winarski prepare an batteries while they are for two types of clogging instrument used to peer charging and discharging. mechanisms. In one, iron inside batteries with the Okasinski explains that originates from porphyhelp of hard X-rays. this type of synchrotron rin-like crude oil molecules, radiation, typically referred and in the other, iron comes from refinto as “hard” X-rays, can penetrate milliery equipment. Researchers previously meters into materials, compared with the had proposed separate mechanisms, but micrometers possible with standard labothe team provided the first direct visual ratory X-ray sources. The extended reach evidence for both (ACS Catal. 2016, DOI: enables scientists to probe a working 10.1021/acscatal.6b00221). battery’s anode, its cathode, and the layer Synchrotron-based X-ray diffraction separating the two in real time and in the has also helped with the design of catalysts presence of electrolyte solution. that scrub nitrogen oxides (NOx) from gas Working with other Argonne scientists, streams, including those emitted by vehiOkasinski used hard X-ray methods in a cles and power plants. Researchers from series of studies on lithium-air batteries. Fudan University developed a nanomateLi-air batteries could potentially provide rial in which NOx-stripping catalyst parmuch more energy per weight than lithticles made of vanadium oxide sit on top ium-ion batteries used in many current of hollow tungsten oxide rods. The team electronics. But Li-air batteries tend to fail designed the rods to trap catalyst-poisonquickly. ing alkali metals and thereby protect the The studies turned up multiple findcatalyst. X-ray analysis of used catalyst ings. First, trace amounts of water in the particles showed that, indeed, the alkali electrolyte solution, likely from electroatoms were trapped inside the rods. lyte decomposition, triggered unwanted reactions. For example, the reactions caused the lithium anode to continuously decompose and form lithium hydroxide. Most people are completely dependent But the news wasn’t all bad. The team also on batteries to power their many gadgets found that the lithium hydroxide layer was and devices. So it’s no surprise that top riddled with microscopic channels that researchers everywhere are working to enabled the battery to continue running— understand why batteries fail and how to albeit weakly—until all of the lithium was extend battery lifetime. Synchrotron usconsumed. ers such as John S. Okasinski, a beamline Overall, the findings suggest that a descientist at the Advanced Photon Source composition-resistant electrolyte would at Argonne National Laboratory near mitigate some of the problems and imChicago, approach the problem by using prove battery performance. ◾
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Project SEED students Edgar Lozano (left) and Helene Hamo are conducting research at Middle Tennessee State University.
COMMENT
Project SEED gears up for its 50th anniversary ANNA CAVINATO, CHAIR, ACS COMMITTEE ON PROJECT SEED
A
fter 48 years, Project SEED continues to impact the lives of young people across the U.S. The program was established by the American Chemical Society in 1968 to provide opportunities for economically disadvantaged high school students to conduct research with a scientist mentor in academic, industrial, or government research laboratories. Students receive a Summer I fellowship in their first year and can return for a Summer II fellowship the following summer. They also receive career counseling and a chance to experience what it means to conduct hands-on research under the guidance of a practicing professional. For many students, this is a life-changing experience. Over the years, more than 10,000 students have participated in the program. By this summer, Project SEED will have placed nearly 400 high school students in more than 140 laboratories across the U.S., where they conduct research under the supervision of volunteer scientists in 38 states, the District of Columbia, and Puerto Rico. Two of these students are incoming seniors Helene Hamo and Edgar Lozano, who are doing research at Middle Tennessee State University, under the supervision of P. Gregory Van Patten. The team is investigating and making new types of quantum dots, which have been identified as candidates in next-generation solar cells, lasers, and other devices. Van Patten has served as a mentor for
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Project SEED students since 2013, and he strongly believes in the impact that the program has on its participants. “The practice of science is not a classroom endeavor, so I believe it’s critical to get interested students involved in the research laboratory as soon as possible,” he says. Samsam Dirie, who is currently a Summer II student and a 2016 ACS Scholar, is doing her research at the University of Minnesota, Twin Cities, under the guidance of Philippe Buhlmann. “I really appreciate this program immensely,” Samsam wrote in a survey that students take at the end of the summer program to evaluate their experience. “It’s super refreshing to work in an academic lab at a research university as a high schooler. At first, I thought my voice and experiment would be disregarded because of my immaturity to research, but once I presented on my work everyone was eager to learn about new findings, from professors, to undergrads, to postdocs. It’s more collaborative and inclusive than I expected it to be.” This fall, Samsam will pursue a degree in chemical physics at Tufts University. Early research experiences such as those offered by Project SEED not only provide the opportunity to explore science careers
but, most important, help build confidence and open the door for students who might otherwise not go on to college. Carlos Huang is a testament of such a life-changing experience. A 2015 Project SEED College Scholar and 2016 ACS Scholar winner, Carlos did his research under the guidance of Carlos Cabrera and José Prieto at the University of Puerto Rico, Río Piedras. He is now entering his sophomore year at the University of Puerto Rico Mayagüez, pursuing a degree in chemical engineering. “It’s a once-in-a-lifetime opportunity filled with many great experiences and lessons,” Carlos states. “Thanks to the program and everyone who’s a part of it because you help promote education in an interesting and fun way. Props to everyone.” As the 50th anniversary of Project SEED in 2018 approaches, the ACS Committee on Project SEED is starting to gear up for this special celebration and has set the ambitious goal of continuing to expand to more states and add programs to states that only have one program. The committee is working hard to promote the program across the U.S. and its territories and find connections in states where the program is not yet established. Of course, for Project SEED to continue to expand and offer educational opportunities for high school students across the U.S., more coordinators and mentors are needed, and more funding is necessary to support the programs. We need your help to publicize the program and recruit new mentors and coordinators. For information on how to host a Project SEED program and recommendations for seeking funds, visit www.acs.org/projectseed. The committee also hopes to count on your generous support. Please donate to Project SEED when renewing your ACS membership and support our fund-raising efforts. Even a small contribution will make a difference! If you would like to learn more about Project SEED and how you can help with its geographic expansion goal, please attend the committee’s open meeting on Sunday, Aug. 21, from 8 to 9 AM at the Philadelphia Marriott Downtown Hotel, Room 305. The committee looks forward to working with you to provide great educational opportunities to students across all 50 states.
Views expressed on this page are those of the author and not necessarily those of ACS.
CRE DIT: GREGORY VAN PATTEN (STUDENTS); GABRIEL LA RODRIGUEZ (ANNA CAVINATO)
ACS NEWS
AWARDS
▸ Phil Baran wins Blavatnik Award Phil Baran, professor and Darlene Shiley Chair in Chemistry at Scripps Research Institute, California, has been named the 2016 Blavatnik Laureate in Chemistry. He is among three winners of the 2016 Blavatnik National Awards from the Blavatnik Family Foundation and the New York Academy of Sciences. The awards honor exceptional young scientists and engineers, and each winner receives an unrestricted cash prize of $250,000. Baran is being honored for his transformative research in the field of natural product synthesis and his development of a new synthetic methodology that enables chemists to design scalable, efficient, and economically viable synthetic routes to potential new drugs. One of the recent successes in the Baran laboratory is the synthesis of the plant-derived ingenol, derivatives of which have been approved by the U.S. Food & Drug Administration to treat skin cancer. The other two Blavatnik awardees are Harvard University astronomer David Charbonneau and University of California, Berkeley, molecular biologist Michael Rape. The award ceremony will take place in New York City on Sept. 12.
▸ Jherian MitchellJones is WCC Overcoming Challenges Awardee Jherian Mitchell-Jones, an undergraduate at the College of Saint Benedict is the recipient of the American Chemical Society Women Chemists Committee’s 2016 Overcoming Challenges Award. The award is given to undergraduate female chemistry students who have overcome significant obstacles in their pursuit
of success in the field of chemistry. As a child, Mitchell-Jones suffered from multiple forms of abuse and developed posttraumatic stress disorder, anxiety, and depression from these experiences, which made it difficult to concentrate in school. Through hard work, therapy, and support from family, she managed her symptoms and was able to succeed in school. She hopes to do research in green energy and fuels as well as in astrochemistry.
▸ Sigal Postdoctoral Fellowship to Lisa Olshansky Lisa Olshansky is the recipient of the 2016– 18 Irving S. Sigal Postdoctoral Fellowship of the American Chemical Society. The fellowship stipend is currently $55,000 a year for two years, and it is awarded to a Ph.D. candidate who is pursuing research at the interface of chemistry and biology. Olshansky earned a Ph.D in chemistry from Massachusetts Institute of Technology in 2015. She will begin a postdoc at the University of California, Irvine, where she will investigate how nature controls the reactivity of metallocofactor intermediates for the oxidation of strong chemical bonds. The fellowship is named for Irving S. Sigal, a chemist who applied site-directed mutagenesis to study the structure and function of enzymes and proteins.
▸ Kay Brummond honored for diversity efforts Kay Brummond, chair of the department of chemistry at the University of Pittsburgh, is the recipient of the 2016 Diversity Catalyst Lecturer award, presented by the Open Chemistry Collaborative in Diversity Equity (OXIDE) initiative. Brummond has revamped the diversity climate within her department by spearheading the introduction of inclusive policies, procedures, and actions. OXIDE aims to change the academic chemistry infrastructure from the top down
by working with the chairs of leading research-active chemistry departments to reduce inequitable policies and practices that have historically led to disproportionate representation on academic faculties with respect to gender, race and ethnicity, disabilities, and sexual orientation.
ACS NEWS
▸ Nominations sought for the 2017 Roy W. Tess Award in Coatings Nominations are being sought for the 2017 Roy W. Tess Award in Coatings, presented by the ACS Division of Polymeric Materials: Science & Engineering. The $3,000 award recognizes outstanding individual achievements and noteworthy contributions to coatings science, technology, and engineering, and it will be presented during the fall 2017 ACS national meeting in Washington, D.C. Scientists from all sectors of industry, government, and academia are eligible to apply and should forward nominations to Theodore Provder, Tess Award Chairman, 5645A Emerald Ridge Pkwy., Solon, OH 44139. Nominations are due on Sept. 1. For more information, contact Provder at (440) 914-0611 or tprovder@att.net.
▸ Call for nominations for Esselen award The ACS Northeastern Section seeks nominations for the Gustavus John Esselen Award for Chemistry in the Public Interest. The award is given annually to a chemical scientist whose scientific and technical work has contributed to the public well-being and has communicated the positive values of the chemical profession. The award, consisting of a bronze medal and $5,000, will be presented at the section’s April 2017 meeting. Nominations should be submitted as a single pdf file and should include a letter signed by the primary sponsor, short supporting statements from two cosponsors, a biography of the nominee, and copies of pertinent articles and popular news and feature articles indicative of public interest. For more information, visit nesacs.org/ awards_esselen.html. Nominations are due by Oct. 15 to karl@amgen.com. Copy jpipergrady@gmail.com on the e-mail.
Announcements of awards may be sent to l_wang@acs.org. AUGUST 8, 2016 | CEN.ACS.ORG | C&EN
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NMR SPECTROSCOPIST Indiana University is seeking qualified candidates for a NMR Spectroscopist at the rank of Research Associate or Assistant Scientist. Classification is contingent upon qualifications and experience. This position assists the NMR Facility Director with daily operations, in addition to maintenance of all instrumentation and equipment in the NMR Facility. Major responsibilities include providing support and training on the operation of NMR instrumentation for users, regular services (including cryogen fills), and troubleshooting of NMR spectrometers, as well as maintenance and update of the Facility’s website. Minimum qualifications for successful candidates are a M.S. degree plus two years of experience in NMR or a Ph.D. with specialization in NMR, comprehensive knowledge of NMR hardware and software, and excellent communication skills. Demonstrated experience with the operation and maintenance of high-resolution NMR spectrometers and strong skills in the use of Unix/Linux operating system is required. Experience in Unix/Linux administration and scripting language programming is also desirable. Applicants should submit a cover letter and CV and arrange for three letters of recommendation to be sent to (https://indiana.peopleadmin.com/hr/ postings/2549). Questions regarding the position or application process can be directed to Dr. Frank Gao, Director, NMR Facility, Department of Chemistry, Indiana University, 800 E. Kirkwood Ave., Bloomington, IN 47405, xgao@indiana.edu. Indiana University is an equal employment and affirmative action employer and a provider of ADA services. Review of applications will begin August 15, 2016 and continue until the position is filled. All qualified applicants will receive consideration for employment without regard to age, ethnicity, color, race, religion, sex, sexual orientation or identity, national origin, disability status or protected veteran status. http://joburl.ws/8347882.
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ASSISTANT PROFESSOR IN BIO-ORGANIC CHEMISTRY, Middlebury College—The Department of Chemistry and Biochemistry invites applications for a tenure-track position to begin September 2017. Ap- plicants should have a Ph.D. in bio-organic chemistry or a closely related field and post-doctoral experience. For details, see http://apptrkr. com/833592. Appli- cation deadline (via lnterfolio) is September 30, 2016. Middlebury College is a top-tier liberal arts college with a demonstrated commitment to excellence in faculty teachingandresearch.AnEqualOpportunityEmploy- er, the College is committed to hiring a diverse faculty as we work to foster innovation in our curriculum and to provide a rich and varied educational experience to our increasingly diverse student body. http://joburl.ws/8347882.
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Curating quirky science since 1943 Faithful falcons in the city
M
oving to a big city can change a person. Newcomers bump into novel experiences and opportunities and pick up new habits and perspectives. A team of biologists wanted to see if this was true for peregrine falcons that started living in Midwest cities over the past few decades. In particular, they wondered whether the birds strayed from mating monogamously. The researchers’ results should warm the heart of even the most cynical Newscripts reader: The city-dwelling falcons remain faithful despite their new urban digs (PLOS One 2016, DOI: 10.1371/journal.pone.0159054). Early in the last century, peregrine falcons lived in cliffs and bluffs along the Mississippi River. But by the mid-1960s, there were no more falcons in the Midwest because of the effects of the pesticide DDT. Starting in the 1980s, scientists tried to repopulate these New in town: majestic birds by breeding Peregrine falcons falcons from other parts of the stay loyal to their world and releasing them into mates even after cities such as Chicago. moving to cities When Isabel C. Caballero such as Chicago. was a graduate student at the University of Illinois, Chicago, she and three other researchers noticed that the birds were nesting closer to each other than they would in more traditional environments. The closer nests increased competition for mates and nesting sites. So did this competition increase infidelity? “Basically, we did paternity tests,” says Caballero, who is now a postdoc at Texas A&M University. Her colleagues collected blood samples from chicks in nest boxes on city buildings, sometimes sporting helmets for protection. “Falcons sometimes punch you in the head,” Caballero says. On the basis of genetic analyses of 350 peregrine falcons from nine Midwest cities Michael Torrice between 1997 and 2009, the team deterwrote this week’s mined that rates of infidelity were low: column. Please They observed just 12 mate changes and six send comments nest changes. and suggestions to Caballero points out that falcon mates newscripts@acs.org.
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C&EN | CEN.ACS.ORG | AUGUST 8, 2016
Toilet paper on the Silk Road
F
or more than 1,000 years, starting around the 2nd century B.C.E., people and goods traveled along the Silk Road, a collection of trade routes that connected China and East Asia with the Middle East and Europe. Now, researchers report the first direct evidence that these routes also passed pathogens between East and West. The critical clue: a 2,000-year-old equivalent of toilet paper. Anthropologists have long thought that diseases such as anthrax, leprosy, and bubonic plague traveled to Europe via the Silk Road, says Piers D. Mitchell of the University of Cambridge. Mitchell studies the history of human migration and the diseases that follow people. To do so, he often looks for parasites at archeological sites. Unlike pathogens, such as the tuberculosis bacterium, that spread directly from person to person, some parasites require living in certain animals for part of their life cycles. If those animals only live in certain places, then scientists can pinpoint the parasite’s geographic origin. In the 1990s, Chinese archeologists excavated a relay station along the Silk Road at Xuanquanzhi in northwestern China. In a latrine, the archeologists found sticks wrapped in cloth. People used these “personal hygiene sticks” to wipe themselves after defecating.
2,000-year-old hygiene: Cloth wrapped around these bamboo sticks was the toilet paper of its time. Because this region is arid, the sticks hadn’t decomposed much. “You still have the cloth around the ends and feces on the cloth,” Mitchell says. When the team analyzed feces samples from the sticks using light microscopy, they found eggs from four different parasite species (J. Archaeol. Sci. Rep. 2016, DOI: 10.1016/j.jasrep.2016.05.010). One, Chinese liver fluke, is found only in wet, marshy areas of Korea and eastern China, a sign that some traveler carried the parasite at least 1,500 km to Xuanquanzhi.
CRE DIT: JOHN W. IWANSKI (FALCON); HUI-YUAN YE H (HYGIENE STICK)
Newscripts
are not only faithful, but they also share hunting and egg-incubating duties: “You could say that the falcons are pretty modern in the sense that the males and females share responsibilities,” she says.
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