Myra Koesdjojo

In 2005, a 23-year-old man went to a rural Burmese hospital complaining of fever. The malaria diagnosis wasn’t surprising. The disease is common in his district, but recent drug therapies have reduced death rates dramatically. The man took the prescribed medicine, artesunate supposedly made by Guilin Pharmaceutical in China. Doctors expected a full recovery.

Three days later, the patient went into a coma. Despite transfers to two other hospitals and injections of intravenous fluids and more artesunate, he died of cerebral malaria.

Analysis of the drug provided by the first hospital showed that it was a fake. Guilin makes authentic medications, but the active ingredient in the hospital’s supply was acetaminophen. A small amount of artesunate was present, about 20 percent of a normal dose, enough to fool a simple test.

Prototype drug detection system

By some estimates, a third to half of the artesunate in some countries is counterfeit. The World Health Organization has called for faster, more accurate tests, and now a team of Oregon State University chemists has stepped up with an innovative approach. They have created an inexpensive paper-based assay that detects a range of artesunate concentrations by turning shades of yellow in the presence of the drug. In OSU’s new Linus Pauling Science Center, this international team of scientists and students is also developing an affordable diagnostic device that can work with the paper test to pinpoint the amount of an active ingredient in a sample.

“We’re trying to develop a simple, rapid and inexpensive method to detect these counterfeits,” says Myra Koesdjojo, who received her Ph.D. in chemistry from Oregon State in 2009 and now manages OSU professor Vince Remcho’s lab. The native of Indonesia knows what’s at stake. Members of her family have had malaria, a disease that kills as many as 900,000 people a year, most of them children in Africa and south Asia.

Fake drugs not only allow patients to die, they also promote antibiotic resistance. By exposing pathogens to ineffective doses of pharmaceuticals, counterfeits enable disease-causing germs to survive and spread, hastening the day when they can outwit front-line drugs.

Koesdjojo and her team envision a portable testing device the size of a cell phone. Health professionals would be able to test batches of drugs quickly and cheaply. The OSU researchers have already built a prototype using off-the-shelf electrical components and open-source software. In their plans is development of an iPhone app.

Paper-based drug detection strip

“We tried a color sensor with an existing iPhone app,” says Koesdjojo. “It works pretty well. But it’s not built for this purpose. We want to use the same idea and develop our own app.”

The team has even greater ambitions: inexpensive, portable devices to detect environmental pollutants and blood-borne diseases. Koesdjojo says her brother would have benefitted. When he came down with malaria, doctors also treated him for dengue fever because the symptoms are similar and they were unable to perform a more precise test.

“Having these simple tools,” she says, “will eliminate the guessing and enable doctors to treat for the right disease.”

International Research Team
Koesdjojo’s team includes students from Oregon and Asia
Jamy Lee, a sophomore in chemistry from Tigard who received an OSU research grant to work in Koesdjojo’s lab last summer

Michael Neilson, a sophomore from Corvallis in physics

Chadd Armstrong, a senior in chemistry from Oregon who received scholarship support from a fund established by OSU alumna Gretchen Schuette (Ph.D., oceanography, ’80).  The Schuette fund supports transfer students as they acclimate to OSU and contributes to student success by promoting contacts between advisers at community colleges and Oregon State.

Anukul Boonloed (Tony), a Ph.D. student from Thailand who has received support from the Thai government for his research. He is helping to develop a collaboration with Chiang Mai University in Thailand.

Parks Remcho, Corvallis High School

YuanYuan Wu, a Ph.D. student student from Dalian, China

OSU undergraduate Sam Bartlett, right, used the tools of organic chemistry — reflux condenser, thin-layer chromotography, nuclear magnetic resonance — to develop a new synthetic chemistry method. He works with Assistant Professor Chris Beaudry in the new Linus Pauling Science Center. (Photo: Karl Maasdam)

With guidance from Chris Beaudry, assistant professor of chemistry, he developed the most efficient and productive method yet reported for a fundamental step commonly used to synthesize new molecules.

Bartlett and Beaudry published their findings in October in the Journal of Organic Chemistry. The research has already drawn the attention of pharmaceutical scientists and has potential in fields from nanotechnology to biochemistry.

“If you’re a synthetic chemist and you want to build complicated molecular architectures – a pharmaceutical, a new material for nanotechnology, a new probe for a biological system – you need to make new chemical bonds,” Beaudry said. “This oxidation is convenient to do, very mild, operationally simple and high yielding. It is the solution to this problem.”

Bartlett’s discovery started with a chance meeting. The student from Corvallis, Oregon, was taking an advanced chemistry course from Beaudry and happened to meet the professor in the Interzone, an off-campus coffee shop. “I asked him if he had any research opportunities in his lab,” Bartlett said.

“I suggested that Sam look into this problem,” Beaudry recalled. “There was some indication that we had a lead hit on how to solve it. Sam took it and ran with it.”

The problem was to convert one commonly used compound (beta-hydroxyketone) to another (beta-diketone). Both are fundamental starting points in the synthesis of more complex organic molecules. Previous methods produced unwanted byproducts and only 30 to 35 percent of the desirable molecule, says Beaudry.

Bartlett found that an oxidant called IBX (o-iodoxybenzoic acid) converts nearly 100 percent of the beta-hydroxyketone to the beta-diketone, thus saving chemists time – and simplifying the synthesis process.

Bartlett, who graduated from Crescent Valley High School, is applying for graduate school, where he intends to focus on synthetic organic chemistry.

“I just like the search for new knowledge,” said Bartlett. “There’s a lot we still don’t know. There are problems out there we still need to solve. Even if I don’t find a solution, I’m contributing to the scientific community.”

Bartlett had support for his research from two programs: the Undergraduate Research, Innovation, Scholarship & Creativity program sponsored by the OSU Research Office, and a Howard Hughes Medical Institute fellowship. He is continuing to work in Beaudry’s lab in the new Linus Pauling Science Center on steps to make a natural plant compound that has potential anti-fungal and anti-inflammatory properties.

Light spectra by artist Stephen Knapp illuminate a wall in the new Linus Pauling Science Center. In their research, scientists use spectra to detect and measure the abundance of chemical elements. (Photo: Theresa Hogue)

In 2011, the first Baby Boomer turned 65 — the leading edge of a wave that is going to change the country. By 2030 one in every five Americans will be older than that. People are already living longer, taking time to travel and to enjoy their families. Think gourmet cooking classes, fishing trips and art museums.

But they will increasingly face the diseases that now kill most people in the developed world: heart disease, cancer, stroke, diabetes and neurodegenerative diseases such as Alzheimer’s and Parkinson’s.

They want answers and solutions. And in the future, many of those answers will come from a new research facility at Oregon State University, the Linus Pauling Science Center.

This new $62.5 million, 105,000-square-foot research and educational structure, just completed this fall, has arrived at an opportune time in American history. But its foundations were laid 94 years ago, in the fall of 1917, when a young student arrived at Oregon Agricultural College and enrolled in a chemistry course. Linus Pauling, OSU’s most accomplished alumnus, went on to win two Nobel Prizes.

“Linus Pauling revolutionized the fields of chemistry and molecular medicine, and this facility will be a working memorial to him, a great tribute,” says Balz Frei, director of the Linus Pauling Institute. “It will help further establish LPI as a national leader in the study of diet, optimal nutrition and micronutrients.

“Chronic disease prevention through diet and lifestyle is the future of medicine,” Frei adds. “And it’s for everyone, not just the elderly.”

Advances in health will come from better understanding of phytochemicals such as sulforaphane, a cancer-fighting compound in broccoli and other cruciferous vegetables. Other research focuses on vitamin D in enhancing immune function and fish oil in preventing fatty liver disease. New types of antioxidants and “anti-inflammatories” are also being investigated, such as lipoic acid, which may be key to getting the most out of life as we age.

Chemical Collaboration

The institute will share the new facility with the OSU Department of Chemistry. Specialists in analytical, materials and organic chemistry will work in close proximity to their peers in the health sciences and develop new strategies for disease diagnosis and treatment. “These new facilities house approximately $10 million in state-of-the-art transmission- and scanning-electron microscopes and nuclear magnetic resonance spectrometers that will serve the entire campus,” says Vince Remcho, chemist and associate dean in the College of Science.

The new instruments were made possible by grants from the M.J. Murdock Charitable Trust, the National Science Foundation (NSF) and partnerships between several of OSU’s colleges, the OSU Research Office and the Oregon Nanoscience and Microtechnologies Institute (ONAMI).

Chemists in the new facility bring with them “an astonishing research track record, as measured by publication count, impact, external funding and intellectual property development,” Remcho adds.

Primary support for the center, which was designed to the U.S. Green Building Council’s LEED silver standards, came from the Wayne and Gladys Valley Foundation – a $20 million gift – and another $10.6 million from Pat and Al Reser. Most of the research in the facility will be supported by grants from the National Institutes of Health and NSF.

“People ask ‘why?’” says Johnson. “I just say, ‘because it’s interesting to me.’ It’s so simple,” he adds, as though he were taking snapshots at the beach, “but you get a lot of information out of it about the molecules.”

Ken Hedberg advises undergraduates Robert Johnson, right, and Luke Costello. (Photo: Karl Maasdam)

For Johnson and Costello, there’s more to it than personal interest and curiosity. They’re solving problems — troubleshooting equipment, puzzling over data with Hedberg, running numbers, reporting results — on their way to bachelor’s degrees in chemistry at Oregon State University. They both plan to attend graduate school and to pursue research full time, Johnson in chemistry and Costello in material science.

Every good coach, whether in baseball or chemistry, focuses on the fundamentals. Hedberg shows his students how to transform solid materials into gasses, generate and guide an intense electron beam the width of a human hair through the gas, record the resulting “diffraction pattern” and use the results to calculate the distances between atoms that define the size and shape of the molecule. To get on base, Costello and Johnson run samples to make sure the machinery is working properly. Convincing evidence of the shape of a complex molecule is a home run.

Hedberg, an OSU alumnus (Chemistry, ’43) and emeritus professor, explains further: “The energy of the electron beam we use is so great that it passes right through the atoms, looks at the nucleus and gets bent around the nucleus. And as these electron waves pass through, they interfere with each other and create a diffraction pattern. That diffraction pattern is what we analyze to determine the structures of the molecules in the gas phase.”

Since he came to OSU in 1956, Hedberg and his students have explored a library of compounds — halides and butadienes, diboranes and cyclohexanes. Unless you’re a chemist, you probably wouldn’t know a halide from an oxide, but in 1993, he and his team were the first to confirm and publish the structure of a newly discovered soccer-ball shaped molecule that had made the headlines: carbon 60, aka the “buckeyball.” Hedberg’s analysis of carbon 60 in the gas phase turned out to be more accurate than studies of its solid form.

In past generations, you would have been hard pressed to find undergrads doing this kind of work. Original research — studies that push the edge of current theory and practice and contribute new knowledge — used to be the domain of graduate students, post-doctoral researchers and the faculty. Undergrads had to get through the basics before they were admitted to the inner sanctum of the lab.

At OSU, as at colleges and universities around the country, Johnson and Costello are part of a movement, undergrads who conduct independent research and original creative work as part of their academic programs. It’s not learning by listen and repeat-after-me. It’s about jumping in with both feet, curiosity-based inquiry under the guidance of people who have been there and remember the thrill of creating something new. In the process, students learn about themselves — their skills, personal goals and career interests — as much as about atoms, the arts, the environment, human health, technology and other fields.

“Independent research teaches you how to work things out yourself and not have somebody hold your hand the whole way,” says Costello, who nevertheless appreciates the supportive, close-knit atmosphere he’s found in the OSU chemistry department. “I have friends who are in big labs elsewhere and end up watching other people’s experiments or doing total grunt work. They’re not doing the actual experimental work.”

Knowing how molecules are shaped, says OSU emeritus professor Ken Hedberg, leads to understanding how they function. (Photo: Karl Maasdam)

And besides, he says, “Ken Hedberg’s a great guy to work for.”

Independence and ownership — what Susie Brubaker-Cole, associate provost for academic success and engagement, calls “a feeling of agency” — define this activity. So does mentorship. In teams or one-on-one, faculty members instruct and guide undergrads through the process of asking questions, designing experiments, analyzing data and creating presentations. This “learning community” of undergraduate and graduate students, post-doctoral researchers and faculty members can become a student’s family away from home, adds Brubaker-Cole. And the faculty link today’s students to academic traditions and culture. In Hedberg’s case, that legacy includes another stellar OSU alumnus, Linus Pauling.

Job on the Home Front

Hedberg grew up in southern Oregon and graduated from Medford High School. In 1943. with an OSU chemistry degree in hand, he went to work for the research arm of the Shell Oil Co. in California on aviation gasoline, synthetic rubber and penicillin extraction, projects deemed crucial to the war effort.

After earning his Ph.D. in physical chemistry and working as a post-doctoral researcher at Caltech, Hedberg came to OSU with strong encouragement from Pauling. OSU Chemistry Professor Earl Gilbert had made a second job offer to Hedberg that spring (Hedberg turned him down the first time), and the young chemist sought Pauling’s advice. One evening, on the veranda of Pauling’s Pasadena home, the Nobel Prize winner urged Hedberg, already an expert in the analysis of molecules by electron diffraction, to accept.

After he came to OSU, Hedberg maintained his friendship with Pauling, and with nearly continuous National Science Foundation support for his research since 1962, he depended largely on graduate students to help him with studies in molecular structure. Although he retired in 1987 and turned 91 in February, the emeritus professor of chemistry continues to work nearly every day in his office and plays an occasional game of tennis. “My wife Lise says she is retired and knows it and that I am retired and don’t know it,” says Hedberg.

Meanwhile, his NSF grants have shifted to support for undergraduates like Costello and Johnson. “They are doing much the same kind of work that my graduate students used to do. It’s lots of fun. These kids are bright, and for the most part, they have been quite interested and productive,” he says.

His goal, he wrote in a 50-year retrospective published in the journal Structural Chemistry, is always to answer a simple question: “Why are things the way they are?” In 2005, after more than five decades of seeking answers through chemical structure, Hedberg traveled to Ulm University in Germany to receive one of the highest honors in his field: the International Barbara Mez-Starck Prize, given to scientists who have made outstanding contributions to structural chemistry.

In addition to his achievements, Hedberg brings something else to his role as a student mentor. Virginia Cross, a 1972 OSU chemistry alumna, recalls that Ken and his wife Lise, a chemist and computer programmer who wrote analytical software for the lab, made students feel welcome. “It was a little family down there in the basement in the chemistry building,” she says. “He respected you to the point of saying ‘what do you think about this?’ He would ask for your opinion even if he could have just told you what he thought. And he was interested in your life, not just the science.”

Cross was a forerunner of today’s trend in undergraduate research. With support from NSF, she spent the summer of her junior year in Hedberg’s lab analyzing sulfuryl fluoride (a pesticide). Success in determining its structure helped her get into graduate school at MIT and led to a paper in the Journal of Molecular Structure on which she was co-author with Norwegian chemist Kolbjørn Hagen and Hedberg.

Currently a resident of Houston, Cross grew up on a dairy farm near Hillsboro, Oregon, and worked in the chemical industry and, until her retirement in 2010, with Richard Smalley, discoverer of the “buckeyball” molecule and a Nobel Prize winner. She has stayed in touch with Hedberg over the years.

National Imperative

Three years before Cross graduated from OSU, MIT created the country’s first campus-wide undergraduate research program. Over the next two decades, Caltech followed suit, the NSF spurred new opportunities with a Research Experience for Undergraduates program and a national conference for undergraduates got under way. That annual event continues to attract student presenters from the sciences, engineering, the humanities and the arts.

At OSU, student opportunities have grown along with the university’s research portfolio, which has more than doubled in the last decade. Little university-wide data is available (monitoring student participation is left to each faculty member, department and college), but personal discoveries are shaping today’s undergraduates in ways their parents could have hardly imagined.

New blue pigments developed in Mas Subramanian’s chemistry lab have attracted commercial interest. (Photo: Karl Maasdam)

An ancient quest for the perfect blue ended in a hot furnace in OSU’s Department of Chemistry — totally by accident.

A blue pigment that is both safe and stable eluded the Egyptians, the Han Dynasty and the Mayans. The French developed cobalt blue in the 1800s, but it contains carcinogens. Prussian blue releases cyanide. Other pigments break down in hot or acidic conditions.

So when Professor Mas Subramanian walked through the materials science lab just as a student opened a white-hot furnace and laid eyes on manganese oxide samples being tested for electromagnetic properties, he stopped in his tracks. “They were blue—a very beautiful blue,” says Subramanian. At nearly 2,000 degrees Fahrenheit, the manganese oxide ions restructure into an unusual “trigonal bipyramidal coordination.”

The intense blue compound holds promise for a heat- and acid-resistant pigment free of toxins. Many of its potential applications — inkjet printers and automobiles, for example — could never have been imagined by those earliest seekers of the perfect blue.

“The concept is to use new, fundamental scientific advances to drive more efficient production and fabrication methods, use green materials and reduce environmental impacts,” says Douglas Keszler, center director and distinguished professor of chemistry at OSU. “The focus will be on electronics and related areas. This is cutting-edge science and technology, and it was born and bred here in Oregon.”

State investment in ONAMI, the Oregon Nanoscience and Microtechnologies Institute, has helped to pave the way for the new center which, if successful, could be in line for up to $25 million in federal funding over the next five years.

Dave Johnson, center co-director and Rosaria P. Haugland Foundation Chair in Pure and Applied Chemistry at the University of Oregon, says that state support for ONAMI was key. “ONAMI investments in facilities, increased ties to Oregon and regional industry, an ONAMI spin-out company and the intercampus collaborations were all key elements in putting together this winning proposal.”

“Among projects sponsored by the Oregon Nanoscience and Microtechnologies Institute, I believe this new center holds great potential for future growth in both the research enterprise and commercial entities,” says Skip Rung, ONAMI president and executive director.