Screenings may have been underreported in part because Hmong women typically keep health decisions private. And while many Hmong have indeed been screened, those screenings tend to be one-time or occasional events rather than regular routines. “It is not enough to have been screened once,” says Jennifer Kue, who grew up in Portland’s Hmong community and conducted the study with Thorburn as a Ph.D. candidate. The risks are especially high among the Hmong, whose cervical cancer rates are some of the nation’s highest.

Another surprising finding: Hmong women make many health decisions independently of their husbands. “In our culture, we place a heavy emphasis on communal decision-making and it’s male-dominant,” Kue, now an assistant professor at Ohio State. “I would have expected men to have more influence.”

The care and feeding of thousands of trout and salmon at OSU’s Salmon Disease Lab are the solemn responsibility of fish biologist Ruth Milston-Clements. (Photo: Lynn Ketchum)

It was dinnertime at the Milston-Clements home. The hubbub of feeding a 6-month-old baby and a hungry toddler was at full clamor when a ringtone interrupted. Handing off the jar of creamed spinach to her husband, Ruth grabbed her cell phone.

“Hello?”

“Ruth, we have a broken pipe.”

As manager of Oregon State’s Salmon Disease Lab, Ruth Milston-Clements is on-call 24/7. With a network of alarms protecting the facility’s 25,000 research fish from disasters both natural and human (power outages, floods, equipment malfunctions, vandalism), she’s accustomed to running out the door at odd times. It happens once a month, on average.

So this dinnertime call seemed fairly routine. A researcher had accidentally backed her truck into a water pipe supplying 30 fiberglass tanks full of fingerlings, the caller reported. Quickly, an onsite technician cranked down the valve to stop the flow. He then rigged a fix that should hold till morning. However, the margin of error between life and death is, for a fish, as thin as a fin. “Without water flow or oxygen, the fish will suffocate in about 20 minutes,” says Milston-Clements, a fish biologist who grew up in Lancaster, England. In her field, there’s no such thing as an excess of caution. So, after tucking her little girls into bed, she spent the next few hours at the lab helping to construct a temporary backup system in case the quick fix failed before morning. It was after midnight when she finally flopped into bed.

The 3 a.m. ringtone blaring from her nightstand jolted her upright. “My heart started beating really loud, and I was hyperventilating,” she recalls. The electronic message from the lab’s security company read: Zone 1, low water. “This is the worst! This is what I’ve been dreading! Thousands of fish could die!” she moaned to her husband as she threw on her sweats and rubber boots and headed out once again.

In fact, no fish died that night. The second alarm turned out to be a minor malfunction unrelated to the burst pipe. But the adrenaline rush highlights what’s at stake in a live-animal research facility.

Crabs Count, Too

Of the 600,000 animals used in Oregon State’s research and teaching programs, 80 percent are aquatic species. Most of these half-million water dwellers are housed in fiberglass tanks on and around the Corvallis campus or at a research hatchery in the Alsea River Basin. Some live in simulated streams or raceways. Still others are on display in touch tanks or seawater aquariums at the Hatfield Marine Science Center in Newport. They come in outrageous colors and preposterous designs: pouty, big-eyed rockfish in shimmery golds and coppers; pincushion-like sea urchins bristling with purple spines; a giant Pacific octopus, its suction-cupped arms undulating around a bulbous orange body. The charismatic Chinook salmon, the elusive black prickleback, the tendrilled basket star, the diminutive zebrafish — more than 400 species in total — all are members of Oregon State’s aquatic animal community.

The care and feeding of thousands of trout and salmon at OSU’s Salmon Disease Lab includes disinfecting brushes after each tank is scrubbed to avoid cross-contamination. (Photo: Lynn Ketchum)

The vertebrates among them are subject to the rigorous protocols of humane treatment laid out by the AAALAC (Association for Assessment and Accreditation of Laboratory Animal Care International) and overseen by OSU’s Institutional Animal Care and Use Committee (see Terra, “The Ethic of Care,” Fall 2012; and “Caring for Cows,” Winter 2013). But the ethical distinction between the spined and the spineless has blurred in recent years. In the same way that the animal-care ethos for rodents and livestock has evolved, so have sensibilities for aquatic animals of all kinds. Just ask Tim Miller-Morgan. In his two-decade career, OSU’s aquatic veterinarian has witnessed an ethical sea change.

Take the case of the ailing crustaceans, for example. Miller-Morgan was moonlighting at the Oregon Aquarium a few years back when he noticed that the spider crabs were lethargic and droopy-mouthed. In the old days, he says, a sick crab would have been euthanized. “The attitude was, ‘It’s only an invertebrate; let’s just get another one.’” But instead of discarding the crabs, he drew their blood and discovered a bacterial infection. He treated the animals with antibiotic injections and medicated feed. “Typically, this wasn’t something that was done,” says Miller-Morgan, who also serves as backup veterinarian for OSU Attending Veterinarian Helen Diggs. “But now we understand that we shouldn’t look at these animals as disposable. We brought them into captivity, and we have an obligation to keep them as long as we can, as close to their natural lifespan as possible — or even longer.”

It’s today’s students, he says, who are driving the new morality. In the aquatic-medicine classes he teaches at OSU’s College of Veterinary Medicine, questions about animal welfare are top-of-mind among the Millennials, also known as Gen Y. “Eight or nine years ago, students started telling me, ‘We’d like to hear information on what we know about fish welfare, how we assess welfare, what do we know about pain?’ That was a new thing.”

He hears the same kinds of queries from students enrolled in the aquarium science program he helped develop at Oregon Coast Community College. It boils down to a centuries-old debate among philosophers, scientists, veterinarians, farmers, ranchers, aquarists, and pet owners: What is our obligation to captive animals?

For researcher David Noakes, the answer is crystal clear. “We have an inordinate responsibility,” says Noakes, who directs the Oregon Hatchery Research Center run jointly by Oregon State and the Oregon Department of Fish and Wildlife (ODFW). “We need to go to extraordinary lengths.”

It’s the Water

Because of the extraordinary lengths taken by Noakes and his staff, international scientists flock to the research center on Fall Creek, a tributary of the Alsea River, which ripples prettily through a mixed woodland of fir, aspens and big-leaf maple. From faraway nations like Japan, China, Iceland and South Korea, they come to conduct studies on the secrets of salmon navigation, the impact of temperature on sexual maturity, the ability of steelhead to negotiate woody debris, and other hot topics in fish biology. “This is the only place on the planet that has everything in one location for salmonid research,” explains Joseph O’Neil, a senior ODFW technician who lives onsite at the hatchery. “It’s the No. 1 destination in the world.”

If O’Neil were to tell you that water is the most critical component for fish husbandry, you might be tempted to say “duh.” But “water” doesn’t come close to conveying the complexity of the systems that support research fish. When O’Neil says, “Fish need water,” he’s not talking about any old water. Whether it fills a 50-gallon fiberglass tank full of Coho smolts, a 40,000-gallon simulated stream stocked with brook trout, or racks of incubation trays, flushing a million salmon eggs at a rate of five gallons per minute, the water O’Neil is talking about is some of the world’s most pampered. Pumped mainly from Fall Creek, this water may be treated with UV sterilization, carbon filtration or aeration so it’s free of viruses and bacteria. O’Neil’s also talking about precise temperature regulation matched to each species’ native environment and each animal’s stage of life. Eight miles of underground pipe circulate up to 2,500 gallons of freshwater a minute and return it to Fall Creek.

Out here in the Siuslaw National Forest, where the nearest town is picturesque Alsea, population 1,153, things do indeed go wrong. The power fails when gale-force winds howl through the hills; the property floods when biblical rains push the creeks beyond their banks; outdoor tanks crack and pipes rupture when branches crash to the ground. The staff takes pride in being able to improvise a solution or jury-rig a repair for just about any piece of equipment, even amidst the wildest squall, wettest deluge or blackest night.

How to Ship a Fish

In Oregon State fish circles, they’re known as “The Two Carries.” The self-described “guard dogs” of OSU’s zebrafish lab, Cari Buchner and Carrie Barton make a solemn commitment each morning when they punch in their pass codes at the high-security building across the river from downtown Corvallis. Tens of thousands of lives hinge on the skill and vigilance of these fish-husbandry professionals.

Cari Buchner, co-manager of the Sinnhuber Aquatic Research Lab, tends the tanks. (Photo: Lynn Ketchum)

Barton and Buchner are co-managers of OSU’s Sinnhuber Aquatic Research Laboratory. The species they oversee — a type of minnow that has been dubbed the “new lab rat” for its growing popularity among biomedical researchers — multiplies fast, matures quickly, shares important disease processes with humans, and rapidly regenerates certain body parts and organs. Best of all, it’s transparent during development. Researchers can see what’s happening inside, literally.

For these reasons, zebrafish make great animal models for medical and environmental research.
“The water here is probably cleaner than most people drink at home,” Buchner attests. That level of purity applies even to water flowing into the staff restrooms, toilets included. If you are granted a visit to Sinnhuber, expect this email in your inbox: “Due to our biosecurity protocols we need to ask that you refrain from any contact with other aquatic species, labs, water sources — especially home aquariums, pet stores and outdoor fish habitats — for 24 hours prior to your visit.” Once you arrive, anticipate being asked to sanitize your hands and slip sterile booties over your shoes.

No one here is taking any chances of jeopardizing the lab’s highly specialized, technically sophisticated, razor-edged enterprise: raising fish that are free of the pathogen Pseudoloma neurophilia, rampant in the commercial aquarium trade and common in many research facilities. “Every fish in this room will be tested for that specific pathogen,” says Buchner. Newly arriving fish are raised, spawned and rigorously tested in a quarantine chamber before their offspring can join the general population.

These uniquely healthy zebrafish are in demand not only at Oregon State but also at other labs. So a couple of years ago, Sinnhuber decided to sell them on its website at a nominal cost. But safely shipping live fish is as tricky as it sounds. The package has to be double-bagged, foam insulated, heat controlled and hand-delivered on the tarmac for transfer to the airplane. For months, Barton and Buchner worked with FedEx, testing various containers and running multiple mock shipments, climaxing with a battery of bumping, shaking, dropping, crushing and tumbling trials.

“The container has to be 100 percent secure,” Barton explains. “It has to hold up even when someone says, ‘Oops, that box fell off the forklift.’” (All this TLC comes at a price, ranging from $50 to $500 for U.S. shipments to $1,700 for international deliveries.)

Soon after becoming a Certified Research Fish Shipper, the lab passed a harrowing real-life test when a container of fish en route to Australia got held up in customs during the hottest part of the summer. Despite an extra five days of travel, the fish arrived in perfect health and were spawning within a fortnight.

Fish Food a la Carte

A “happy tank” is the gold standard in a fish lab. When Ruth Milston-Clements lifts the lid of a tank and sees the sleek, silvery smolts schooling round and round in vigorous uniformity, she can rest easy. But if the fish are “dancing” or “flashing” or “looking a bit itchy,” she immediately calls in the lab pathologist. The telltale signs of trouble recently showed up among some rainbow trout. A scale swipe revealed a parasite called Gyrodactalus. She treated the tank with a hydrogen peroxide solution and monitored the fishes’ behavior every 10 minutes for an hour. They revived. Happy tank.

Carrie Barton, co-manager of the Sinnhuber lab, feeds Artemia nauplii, a juvenile form of brine fish, to zebrafish schooling in a stock tank. (Photo: Lynn Ketchum)

Fish like it when someone lifts the lid on their tank. That’s because it usually means mealtime. Over at Sinnhuber, the two Carries show off their brand-new commercial-grade kitchen where they concoct customized diets to researchers’ specs.

The proteins, carbs, oils, vitamins and minerals are tightly calibrated for optimal animal health. For many studies, researchers order special formulas. One of those researchers had a terrifying jolt a week before Christmas when he discovered his supply of custom fish food wasn’t going to last through his experiment. So while most people were baking gingerbread cookies and fig puddings, Barton was down at the lab whipping up an emergency ration of experimental fish food. “I went into my superhero mode,” Barton says with a satisfied grin. She saved the day — and the study.

“Basic care for aquatic animals is much more intricate than it is for most mammals,” she observes. “It’s really a science unto itself.”

Women in Pabna, rural Bangladesh, carry drinking water in large containers. (Photo: Molly Kile)

Fighting a war of independence should be turmoil enough for a small country, but in 1970, the people of Bangladesh also had to deal with a deadly cholera outbreak. This water-borne disease threatened the country’s plentiful surface water and put public health at risk. To solve this crisis, the government, together with international aid agencies, dug thousands of wells. But the clean water they hoped to deliver created a new crisis, what one researcher calls the largest mass poisoning on the planet.

Fast-forward 20 years. Symptoms of arsenic toxicity were beginning to appear in the population. Skin lesions were misdiagnosed as leprosy and led to social exclusion. Worse, skin lesions are a potential precursor to cancer.

Molly Kile, an environmental epidemiologist at Oregon State University, and her Harvard mentor David Christianie first traveled to Bangladesh in 2003 to study the health effects associated with arsenic in drinking water. “Our efforts have largely been understanding the epidemiology (of arsenic exposure) and the human health risk associated with it,” says Kile. She first traveled to Bangladesh as a doctoral student at Harvard and has returned more than 20 times.

Molly Kile studies the health impacts of environmental contaminants. (Photo courtesy of Molly Kile)

Scientists know that exposure to high levels of arsenic can lead to cancer, but Kile, an assistant professor in the College of Public Health and Human Sciences, wants to know how the metal affects other aspects of health, such as reproduction and child development. Local groups, she says, can effectively translate her results into disease prevention, but many participants in her research are among the most vulnerable in the country.

“By and large, the populations that are affected by arsenic in Bangladesh are the rural populations,” she says, “and about 60% of Bangladesh lives on less than $2 a day. So these are places of absolute poverty.”

Reproductive health effects stem from the fact that the toxic metal crosses the placenta and exposes the fetus. Low birth weight and spontaneous abortions have been associated with arsenic exposure in utero. Kile also uses genetics to look for variations among individuals that increase or decrease susceptibility to skin lesions.

Perhaps the most frightening aspect of arsenic is its invisibility. “You can’t taste arsenic. You can’t smell it, you can’t see it, you have no idea its there unless you test for it,” she adds.

Binding Arsenic

Not being able to detect arsenic by sight or taste has raised the stakes for communities that lack the resources to test or treat their drinking water. Kile’s favorite way to test for arsenic in people may come as a surprise: the human toenail.

Toenails are composed of keratin, which contains chemical combinations of sulfur and hydrogen called sulfhydryl groups. As arsenic in the body binds with these sulfhydryl groups, it accumulates in the toenail.

“So keratin is mostly sulfhydral, as is your hair,” says Kile. “Any inorganic arsenic that is circulating in your body will want to bind to a sulfhydral group. So your toenails, your hair, and even your skin all come into equilibrium with the arsenic in your body. You can take a toenail clipping, and you get a lovely integrated exposure of what that person has been exposed to.”

Molly Kile met with residents of Dhaka Community Hospital to discuss her studies of arsenic exposure. She and her team ask what concerns people have and recruit participants in their research. Their findings are then shared with the community. (Photo courtesy of Molly Kile)

Kile calls the health crisis in Bangladesh a preventable disaster. Arsenic was known to be present in large parts of western Asia, but that wasn’t considered in the 1970s when the country transitioned to groundwater.

“And it was seen as the public health triumph of its day, only to find out that it’s now the largest mass poisoning on the planet,” says Kile. “That’s one of the messages of this: This was completely preventable.”

Research elsewhere suggests that as exposure declines, skin lesions may go away with time, but such studies are still in progress.

Despite Kile’s start with arsenic being half-a-world away, the issue isn’t so far from home. She calls Oregon “arsenic country” and has been conducting water-testing workshops in communities east of the Cascades. In the United States, technology can remove arsenic from drinking water. So far, there have been no arsenic-related health problems recorded in Oregon.

“It really is across Oregon,” she adds. “Eugene, Salem…and across the border too. This is a Pacific Northwest Issue.”

Scientists estimate that up to 100 million people are exposed to elevated levels of arsenic in Bangladesh alone. Whether you are drawing from a well in Bangladesh or Oregon, researchers like Kile are racing to fully understand the impacts of this invisible contaminant.

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Listen to a podcast with Kile.

For more information about arsenic in drinking water in Bangladesh:

D. van Halem, S. A. Bakker, G. L. Amy, and J. C. van Dijk, “Arsenic in drinking water: a worldwide water quality concern for water supply companies,” in the Journal Drinking Water Engineering and Science, 2009,

Manouchehr Amini; Karim C. Abbaspour; Michael Berg; Lenny Winkel; Stephan J. Hug; Eduard Hoehn; Hong Yang; C. Annette Johnson; “Statistical Modeling of Global Geogenic Arsenic Contamination in Groundwater,” Environ. Sci. Technol.  2008, 42, 3669-3675.t © 2008 American Chemical Society

Chowdhury, M. A. I., Uddin, M. T., Ahmed, M. F., Ali, M. A. and Uddin, S. M.: How does arsenic contamination of groundwater cause severity and health hazard in Bangladesh, J. Appl. Sci., 6(6), 1275-1286, 2006

Heidi Igarashi studies the “sandwich generation,” parents who care for their adult children as well as their own aging parents. Listen to a podcast with Igarashi. (Photo: Nick Houtman)

For many first-year college students, going to a new school represents “leaving the nest.” They are now responsible for housing, bills and their own education. But according to Heidi Igarashi , a research assistant at Oregon State University, most are still in their parents’ nest and will be for several more years.

“Parents used to expect that their kids should be financially independent by 22,” she says, “but now the majority of them say 25. There is a longer run up to adulthood.”

Igarashi, a doctoral student who works with Carolyn Aldwin, professor of human development and family sciences, recently published a study looking at parents who support both adult children (ages 18 to 30) and their own elderly parents. She found that while parental support may benefit maturing adults, things get more difficult when they care for the older generation.

“The idea of the empty nest is based on this probably antiquated idea of the life cycle where you get married, have children, your children grow up, ‘leave the nest,’ and the parents are there to ride out those last periods of time. ‘Empty nest,’” she adds, “applies to some people but not many.”

It is simply taking longer for young adults to take flight. That trend shows up in a variety of ways, from education to insurance.  For example, Igarashi points to an increased interest and a need for further education in graduate school.  Health insurance has also changed. Prior to 2010, states had varying rules on dependency for health insurance purposes. Now federal law says a child can remain on a parent’s insurance until age 26. Igarashi attributes these cultural changes to the nest being full longer.

Igarashi found that most parents were happy to support their children for longer periods of time. Parents, she suggests, are simply continuing what they had been doing. However, she also looked at them as caregivers for their own parents. This type of caring is increasingly common. The average couple has more parents than children. But that doesn’t mean it is always received with ease. Igarashi calls this type of support “caring up.” On the generational ladder, the older you get, the higher on the ladder you are.

Caring Up Is Hard to Do

“Caring up is hard on everyone. The midlife folks were very happy to provide care up, but it came with this burden, feelings of angst, anxiety, uncertainty. Not only for themselves, but for their parents too.” Some elderly parents had Alzheimer’s, and some were bed ridden. In these circumstances, feelings of anxiety are natural, she adds.

Igarashi did her study during the economic recession of 2008-2009. Shortly after she published her results, the PEW Research Center released a similar but separate study that added more detail. PEW found that in 2012, 47% of midlife adults (ages 40-59) were supporting a child, while they were also taking care of a parent older than 65-years-old. Pew Researchers referred to these individuals as part of a “sandwich generation,” meaning they provide both care up and care down the generational ladder.

Despite any feelings of potential burdens, Igarashi’s study found that during these changing economic times, being a “sandwich generation” may not be a bad thing. Young adults get the support they need to take flight from the nest when they are truly ready, whether for educational, financial or other reasons.

“In our society we tend to really value autonomy and independence, and hold it almost paramount to almost anything else,” says Igarashi. “What our study indicates is that it’s really interdependence that may become really important, especially in this changing socioeconomic world where you really need other people around you to really work together.”

Most college students fit into the category of nestlings learning to fly. While the job market will continue to create challenges, Igarashi provides encouragement that parents are willing to assist their children during these changing times even while assisting parents of their own.

Co-authors on Igarashi’s study include Oregon State professor Karen Hooker, Deborah P. Coehlo (OSU-Cascades) and Margaret M. Manoogian (Western Oregon University).

_______________________________

See Igarashi’s report, “My Nest Is Full”: Intergenerational relationships at midlife, in the Oregon State University Scholar’s Archive.

See the PEW Research Center study on mid-life adults: http://www.pewsocialtrends.org/2013/01/30/the-sandwich-generation/

Researcher Aurora Sherman (left) and graduate student Pamela Lundberg use a Mrs. Potato Head toy to study girls' attitudes about female identity and roles. (Photo: Jeff Basinger)

Sex may sell everything from magazines to perfume, but the effects of pervasive sexuality in marketing and consumer products go far beyond the cash register.

In 2007, the American Psychological Association released a report — APA Report on the Sexualization of Girls — on the impacts of media displays of women as sexual objects. It summarized what psychologists know about how exposure to sexualized images harms children and teens — depression, lowered aspirations, eating disorders, lack of assertiveness, unhealthy sexual behavior, dissatisfaction with their own appearance — and offered recommendations to counteract them.

Two developmental psychologists at Oregon State University are exploring the consequences of sexualization for child development. A team led by Aurora Sherman is delving into girls’ career aspirations. She is asking how exposure to the impossibly proportioned but ever popular Barbie™ might affect their career choices. At OSU-Cascades in Bend, Elizabeth Daniels has focused on media portrayals of women in sports. Her studies contrast the effects of sexualized images with those that show women engaged in athletics.

Taken together, their results have implications for parents and youth organizations. They suggest that it takes media savvy and strong role models to promote healthy development in the face of what the APA calls “the massive exposure to portrayals that sexualize women and girls and teach girls that women are sexual objects.”

Choices for Girls

Among successful dolls, Barbie™ tops the list. The manufacturer, Mattel Inc., estimates that one is sold somewhere in the world every three seconds. According to the website barbiemedia.com, the doll’s inventor, Ruth Handler, wanted a doll that would expand opportunities for girls. “Barbie always represented the fact that a woman has choices,” she said.

When the APA report came out, Sherman remembers being startled on reading that so little research had been done on the influence of dolls on girls’ development. “If we’re going to have this conversation about sexualization, how can we overlook the most widely sold plaything on the planet?” she says.

Surprisingly, psychologists are only beginning to look closely at how dolls affect girls’ psychological health — their aspirations, self-confidence, body image and mood. And dolls are just one element of the popular culture that helps to shape attitudes and personality. TV, video games, movies, magazines and websites blare messages about what it means to be a woman or a man and what social expectations stem from gender.

“Toys are just one part of the socialization process,” says Sherman, an assistant professor in OSU’s School of Psychological Science. “But they are a very important part. Barbie displays adult features, and girls love to imagine what it would be like to be an adult.”

So, in looking at how dolls affect girls’ career choices, Sherman chose to use Barbie™ in her research. She and her collaborator, Eileen Zurbriggen of the University of California, Santa Cruz, (and chair of the APA task force that produced the 2007 report) designed an experiment in which 37 4- to 7-year-old girls were randomly assigned to play with either a Barbie™ or a Mrs. Potato Head doll for five minutes. The girls then answered a series of questions about career choices in 10 fields, five typically held by men and five by women.

The results showed that playing with Barbie™ had a clear impact on girls’ career perceptions. Girls who played with the Potato Head doll did not make a distinction between the number of jobs that girls and boys could do. However, those who played with Barbie™ tended to think that more careers are open to boys than to girls. “It’s difficult in social science to find an effect with this kind of treatment,” Sherman says. “I was astounded that after so short a time, the girls who played with the Barbie reported such an effect.” The team’s paper has been submitted to the journal Sex Roles.

The focus on youth is a change for Sherman who has specialized in health, social relations and aging. To find girls willing to participate, she worked with Corvallis-area families to explain the nature of the project. “Parents run the gamut from a strong dislike of Barbie to strongly liking her,” she says. “I was careful to remain neutral, so I didn’t inadvertently bias the pool.”

Sherman is continuing her work on the influence of dolls with support from the John C. Erkkila, M.D. Endowment for Health and Human Performance at Good Samaritan Hospital in Corvallis. Her focus is on the impact of sexualized dolls — Barbie™ as well as Bratz™ dolls (a more sexualized line of dolls made by MGA Entertainment) — on body satisfaction and self-esteem.

Sherman hopes to promote thoughtful discussion about the issues raised by these dolls. “Barbies are here to stay,” she says. “They’re a very loved, more than 50-year-old cultural icon. They’re very engaging dolls. They’re serving some kind of need for girls. So what can we do with kids and parents to minimize whatever the detrimental impact might be? If we’ve got a very well-beloved plaything, what can we do to make it work for us?”

Women in Sports

Athletics can build girls’ self-esteem and confidence, says Elizabeth Daniels, but media portrayals of female athletes can have the opposite effect. They fall into two categories: images of women performing a sport and images of female athletes in sexy poses. “Over the past four decades or so, researchers have studied how female viewers are affected by idealized images of women (i.e., thin, airbrushed, ‘sexed-up,’ etc.),” Daniels explains. “In general, these images make female viewers feel bad about their own bodies. Almost no research has investigated how female viewers respond to alternative images of women, e.g., female athletes depicted as athletes.”

At OSU-Cascades in Bend, Elizabeth Daniels (standing) leads an undergraduate research team of Brent Reynolds (left), Desiree Jackson, Taylor McGowan and Emily Clark. (Photo: Steve Gardner)

Sports is an important domain for youth and increasingly for girls. Since passage of Title IX in 1972, the participation of high-school girls in athletics has skyrocketed. Today, girls comprise 42 percent of all high-school athletes, and about 180,000 women play college sports.

Unfortunately, media often emphasize female athletes’ sexual, rather than athletic, qualities. For example, just before the winter 2010 Olympics, the Sports Illustrated swimsuit edition featured skiers Lindsay Vonn and Lacy Schnoor as well as snowboarders Hannah Teter and Claire Bedez in bikinis. Swimmer Amanda Beard appeared nude in Playboy. Tennis player Anna Kournikova is the only athlete to be named by For Him Magazine as the sexiest woman in the world.

Daniels speculates that profitable endorsement deals may influence some athletes. “Athletes have limited opportunities to gain endorsements, which are far more lucrative than their salaries,” she says. “The few endorsement opportunities that do exist for elite female athletes might require a focus on the athletes’ sexual appeal. Some female athletes may agree to participate in a sexualized photo shoot because of a lack of alternatives.”

In her studies, Daniels worked with high-school and college-age students. She showed them images of female athletes performing their sports, photos emphasizing their sexual qualities and sexualized images of models who are not athletes. She asked participants to respond in an open-ended format to elicit their opinions and feelings about the images. “An open-ended format opens up the possibility of responses that I could not have predicted,” she says.

Daniels found that both boys and girls tend to dismiss or devalue the athletic abilities of female athletes portrayed in sexualized images. In contrast, performance images of strong female athletes elicited a positive response. Both boys and girls respected these women’s strength and skills. Girls recognized the athletes as strong role models.

Taking Action

Images of women performing their sport “could be a powerful counterweight to the overly thin standard portrayal of females currently dominating the media,” Daniels wrote in the Journal of Applied Developmental Psychology. “As educators, parents, and social activists call for a change in the content of problematic media,” she adds, “there is a need to suggest alternative imagery such as female athletes depicted as athletes. My research provides the evidence that these images have a positive impact on youth.”

To help girls understand and counter sexual stereotypes, Daniels has shared her results with community and professional groups. She has worked with the Bend chapter of Girls on the Run, an international organization that pairs running with information about nutrition, emotional heath and other elements of healthy youth development.

Daniels has expanded her research beyond athletics. She has found, for example, that boys and girls make positive evaluations of images of accomplished women in business and the military.

She is currently examining how girls are judged on social media sites such as Facebook. To date, she has found that girls who use sexy profile photos are perceived negatively by other girls. They are in a tough position, she explains. “They’re inundated with all these media telling them to be sexy and hot, but they are still developing the cognitive skills to understand what happens if they do that.

“We need to have a counterweight to the negative idealized images that create so much dissatisfaction,” she adds. “We need to do a much better job educating youth and families about how to manage media in their lives and to cultivate positive attitudes toward the body.”

Human Development and Family Studies Ph.D. student Sara Schmitt is finding out just how much.

“One of the primary studies I’ve been involved in here at Oregon State is trying to develop a screening tool that parents, teachers and researchers can use to see how ready kids are for school in terms of their self-regulation or self-control skills,” she says.

Games provide a way to test children's readiness for school. (Photo: Alan Calvert)

Led by Schmitt’s mentor, Associate Professor Megan McClelland, Schmitt has been working on two large studies. One, funded by the U.S. Department of Education, focuses on developing a screening tool for young children that will help prepare them for school entry. The other is an intervention to help children practice the skills they need to be ready for kindergarten.

“In both of those projects, Sara’s been an invaluable part of our research team,” McClelland says. “She’s a graduate research assistant and has worked just unbelievably well with parents, teachers and all of our staff.”

Schmitt always knew she wanted to work with children in some sort of capacity, but it wasn’t until she joined an AmeriCorps team that she realized how she would do so.

“As an AmeriCorps volunteer, I worked at a homeless shelter and taught preschool classes there as well as tutored school-aged children,” she says. “It was at this point that I realized that these kids were really behind, both behaviorally and academically, and I knew that I wanted to devote my career to researching ways to help children from disadvantage.”

Her work as a volunteer was the perfect training for her current research at the child development laboratory.

“We can take this knowledge and develop interventions that we can take into the community, particularly communities that may have children at risk for poor developmental outcomes,” she says.

Sara Schmitt would like to create a screening tool to see how prepared children are for school. (Photo: Alan Calvert)

The types of skills Schmitt studies include children’s ability to pay attention, to persist on tasks, to remember instruction and rules and to inhibit responses. An example of this is remembering to raise a hand rather than blurting out an answer.

“We primarily play really fun games with the kids that allow them to practice these skills,” she says.

One game they play is the red light/green light game. First, Schmitt asks them to play in the traditional way, where red means stop and green means go, but then she adds and changes rules. By doing so, children have to adapt, remember, pay attention and abide by the new rules.

Another game Sara plays is a variation of “Simon Says” – or in her case, “Sara Says.” In this game, children perform the action asked of them when Schmitt says “Sara Says,” and don’t perform it when she doesn’t say “Sara Says.” The point of this game is to help kids stop, think and then act.

“What we learn from this work is where kids are at in terms of their school readiness,” she adds. “What we can do with that is provide interventions for children who are really struggling with these skills.”

In a recent study, Schmitt and her team of researchers played these games with children at a school over eight weeks. They found that kids who participated in the games did better at the end of their preschool year.

The researchers also provide parents and teachers with a list of games in hopes that parents will play with their children at home. Teachers could use the games in the classroom as a way to prepare kids for school.

“Not only do I want to continue this pathway of research and try to figure out ways to help kids from at-risk backgrounds, but I’m also looking forward to engaging undergraduates in my work, teaching them how to work with children in school settings, how to parent in successful ways, and to promote whatever career that they want in child development,” Schmitt says.

Ph.D. student Sara Schmitt is in the Human Development and Family Studies program at Oregon State. (Photo: Alan Calvert)

Schmitt’s graduate training is setting the stage for her future as an academic. She would like to turn this pathway of research into a faculty position at a university.

“I think Sara has enormous potential to be such a successful researcher and teacher,” McClelland says. “She and all of our graduate students here in HDFS have just received such excellent training in the College of Public Health and Human Sciences to form a foundation for a really successful career.”

“Promoting school readiness for children at-risk not only helps them do better in school, but lays the foundation for a healthy and successful lifelong trajectory, which means the world to me,” Schmitt explains. “I think about those homeless kids I worked with back in the AmeriCorps year, and I just know that they needed so much more support than I could offer. I hope to continue to do this work and help these kids do better in school and have an overall healthy life.”

“All who care for, use, or produce animals for research, testing or teaching must assume responsibility for their well-being." Guide for the Care and Use of Laboratory Animals, 2011, The National Research Council. (Photo: Frank Miller)

The three rats snoozing in Cage 57 don’t know it, but they could someday help save thousands of human lives.

Snuggled in their EcoFresh bedding, the rodents are digesting a meal that may hold clues to preventing colon cancer, the second-leading cause of cancer deaths in the United States. On their cage, equipped with HEPA air-purification filters and precision temperature controls, hangs a blue index card labeled “Special Diet,” on which a researcher has scrawled “Bruss” in black felt pen. The scrawl is short for Brussels sprouts, those oft-disparaged veggies resembling tiny cabbages that are loaded with promising cancer-prevention compounds such as sulphoraphane.

To the rats, however, the pale-green pellets in their food tray (Mix AIN93 from Research Diets Inc., with sprouts added) are just dinner. That dichotomy — the rats’ bodily, mental and social needs (rodents are housed with “buddies” for company and “crawl tunnels” for enrichment) versus the precise methods of science — requires researchers to walk a tightrope, always balancing the pressing questions of medicine, for example, against the welfare of animals. The results are key to curing devastating diseases like ALS or Alzheimer’s.

Oregon State University, with 600,000 research and teaching animals (mostly fish and other aquatic species) at 30-plus sites across the state, is balancing those interests exceedingly well. That is the judgment of the Association for Assessment and Accreditation of Laboratory Animal Care International (AAALAC), which in March gave a glowing report after an extensive accreditation study (see “High Grades for Animal Care“). Oregon State is the 19th among the nation’s 71 land grant universities to earn full-campus AAALAC accreditation.

The snow-white, sprout-eating rats in OSU’s state-of-the-art rodent facility are just one among 400 vertebrate species that populate the university’s labs, barns, aquariums, ranches and hatcheries. Zebrafish, steelhead, beef cattle, garter snakes, rainbow trout, dairy cows, yellow- and red-legged frogs, copper and canary rockfish, lambs, koi, swine, salmon smolts and llamas are among the half-million-plus warm- and cold-blooded creatures that help educate OSU’s students, improve health (both human and animal), protect ecosystems, guide resource management, bolster local economies and engage the public.

Every last one of these creatures, from the 2-inch trout fingerling to the 2,000-pound Hereford bull, is the responsibility of Dr. Helen Diggs. If you don’t have an electronic key card, you must knock at a security door to gain admittance to her building on the west end of campus, the base from which Oregon State’s attending veterinarian oversees her vast menagerie. With the welfare of thousands of animals on her mind, she is quick to question, slow to trust (or, as she likes to say, “I trust but verify”). It’s a hyper-vigilance honed over 25 years in the field, some of those years at UC Berkeley where Diggs endured threats from animal-rights activists and had to be escorted to her car by security guards.

Tacos and M&Ms

“This is my morning health-status report,” says Diggs, pointing to a spreadsheet on her computer monitor. “Every day, every animal-facility manager checks in with me. Here’s Chad Mueller at the ag experiment station out in Union. Here’s Rob Chitwood at the fish performance lab over by the golf course. Here’s the Linus Pauling building. The Oregon hatchery. The Horse Center. Wherever I am, I can open up this online report and see what’s happening.”

So when a hamster is lethargic or a horse is lame, she’s on it. But practices haven’t always been so rigorous in the world of animal research. Diggs has been in the field long enough to have seen the transformation.

“In the decades before the 1980s, some universities were not caring for their animals as well as they should,” says Diggs, who has overseen research animals since 1985. “The facilities smelled gnarly. There were wooden floors with urine stains, poor temperature control. Regulations weren’t being enforced. No one was watching.”

This laxity was not just a problem for the animals. It was also a problem for the science.

“Researchers weren’t able to repeat their results. If I’m keeping my rats in a closet and feeding them oatmeal for breakfast, while your rats are getting leftover tacos or pancakes from the student lounge, we can’t validate our findings.”

Adds Steve Durkee, another of the university’s leading research-animal watchdogs: “If rats in one study are getting cereal while those in a second study are getting oranges and M&Ms, you can’t compare the results of the studies. By standardizing and harmonizing how animals are cared for, you create consistency across labs and institutions.” In fact, he notes, prestigious academic journals publish only findings that document the highest standards of animal care.

That’s why Diggs’ job has teeth. Sharp ones.

“I can shut a program down,” she says. “I’ve never had to do it here. But two times at other universities, I had to actually shut someone down and lock the door. If I have to go in and have a conversation with someone about their animal work, they’ll listen to me. It’s a big deal.”

Technicians and researchers rely on rodents and other animals to unlock biological mysteries. (Photo: Frank Miller)

Even though the U.S. Public Health Service mandated in the early ‘70s that all animal research institutions hire an attending vet, the top docs didn’t have any real enforcement power until the mid-‘80s. That’s when the National Institutes of Health and the U.S. Department of Agriculture cinched up the rules for labs getting federal research dollars.

“Attending vets had no real authority back in the early days,” explains Diggs, who reports to Rick Spinrad, vice president of research at Oregon State. “Some didn’t even have keys to the animal facilities. You need someone who’s minding the store, not just a figurehead.”

Minding the Store

Bob Murray waves his key card in front of a laser-triggered security panel in the $62.5 million, 1-year-old Linus Pauling Science Center, which houses the Department of Chemistry as well as the Linus Pauling Institute. The elevator opens, and he steps inside. One floor down, he flashes his card again, clicking open an electronic steel door into a small anteroom, where he slips on a gauzy yellow “isolation gown” and a pair of puffy blue booties.

For a third time, Murray brandishes his key card, unlocking yet another heavy door. He enters the inner sanctum of Oregon State’s gleaming “vivarium” — the small-mammal equivalent of an aquarium or a terrarium — where hundreds of rats and thousands of mice live, as well as a few hamsters. Not one of these furry beings can get a sniffle or a sore toe without Murray knowing about it.

“The animals are checked at least twice a day, 24-7,” says Murray, who clocked 35 years in the field, working at the New England Primate Center, Walter Reed Army Medical Center, Letterman Army Medical Center, UC Berkeley and Genentech before coming to OSU last year to manage the lab-animal facilities. “We watch for changes in gait or overall appearance — does the animal’s coat look scruffy? How is the animal’s appetite and hydration? We look for lethargy, weight loss, tumors. Any health problems we report immediately to Dr. Diggs and the researchers.”

The vivarium maintains strict controls on temperature and other factors in the animals' environment.

Murray’s dad worked for the Society for Prevention of Cruelty to Animals in Boston for nearly 30 years. So worrying about animal welfare is practically in his genes.  He takes pride in the life-saving research he has observed over the years, like the groundbreaking Herceptin research at Genentech that is being used to treat thousands of women with breast cancer and the malaria vaccine research at Walter Reed. Still, it’s the health and comfort of the whiskered rodents that gets him out of bed every morning at 5 o’clock and keeps him running as he oversees his team of highly trained, certified animal technicians.

“I believe strongly in the value of the research we do here, but I’m not a researcher,” Murray says, surveying his domain with the discerning gaze of a seasoned professional. “I’m into animal care.”

If Murray were to take you through the 8,000-square-foot facility where researchers investigate the links between nutrients and human health, the first thing you would notice is an obsession with cleanliness. The giant Steris cage washer (which he calls “the heartbeat of the whole facility”) sanitizes racks of cages in two cycles of 180-degree, pressurized water — and that’s after the cages have been blasted with detergent and rinsed in acid. Everywhere you look, technicians and student workers are prepping cages for incoming animals or plying mops on floors that already look immaculate. Viruses and bacteria that could sicken the animals and compromise the research don’t stand a chance.

The next thing you would notice is the attention to precision. Automated lighting simulates 12 hours of day, 12 hours of night. Electronic monitors maintain a 68- to 72-degree temperature range. An alarm alerts the staff if temperatures fall outside the range by even 1-degree Fahrenheit. There are ventilation tubes, fume hoods, stainless-steel work stations illuminated with stretchable spotlights. Every last facet of the facility is designed to protect the health and welfare of all its mammalian inhabitants, human as well as rodent.

Not until you reached the bosom of the vivarium would you come upon the rodents. The Brussels sprout-eating residents of the “rat room” were born and raised at an Indiana-based research-animal supply company called Harlan Laboratories, arriving at OSU in ventilated crates via UPS. Firms like Harlan, along with Charles River Labs, Jackson Labs and dozens of others comprise a global mega-industry in the service of science. All must adhere to the same stringent federal requirements that guide OSU’s animal-care personnel.

Diets supplemented with cancer-fighting compounds are under investigation in the Linus Pauling Science Center.

In the rat room where Rod Dashwood and other researchers in the LPI Cancer Chemoprotection Unit are looking for evidence that cruciferous vegetables like Brussels sprouts and broccoli sprouts can block the formation of colon tumors, dozens of clear-plastic cages are stacked, one above another, inside tall metal racks like high-rise condos. When you lean close and peer inside, you’re likely to get a visual jolt.

The cold, hard sterility of biomedical science is, you realize, wrapped around hundreds of breathing beings with whiskered snouts and beating hearts. They cuddle together for warmth and companionship. They look out at you with the pinkish eyes characteristic of albino Strain F344, understanding nothing about the scientific enterprise in which they play the leading role.

A Fish Like Me

So why do scientists work with animals? What can rats (Rattus norvegicus) or zebrafish (Danio rerio), seemingly so far from Homo sapiens on the tree of life, reveal about human health and disease? Turns out, many basic biological processes such as cell division, organ differentiation, gene mutation and disease formation play out similarly across species. That’s why a rat or a mouse or a fish can act as a stand-in for a human in studies on micronutrients, obesity, aging, ALS, cancer, drug efficacy, infectious disease and any number of other biomedical questions under investigation at Oregon State.

When researchers use rats, mice or other species to study processes that mimic or parallel human biology, they call it a “model.” One common model is a “knockout mouse.” It works like this: To gauge how certain genes affect certain bodily functions or disease processes, researchers “knock out” or silence the targeted gene and then study what happens when the mice get, for instance, a high-fat diet or a hormonal supplement. Knockout mice are used at OSU to study bone growth, aging, obesity, immunodeficiency and many other intricate areas of human health.

But complex animals like mice and rats are used only when there’s no other way to investigate the question at hand, Durkee stresses. Indeed, basic biomedical research begins with cells in a test tube. Only after experiments have shown great promise do scientists advance to animal work. And then, only after the animal studies achieve high rates of treatment success or cures — along with low risks for harm  — do scientists go on to conduct experiments on humans. Steve Durkee’s mother was a subject in one of those experiments, which researchers call “human” or “clinical” trials, when she was battling breast cancer.

Durkee likes to direct people to the AAALAC website’s long list of Nobel Prizes in medicine and physiology over the past 110 years. Without the use of lab animals, Frederick Banting and John McLeod wouldn’t have discovered insulin and the mechanism for diabetes, winning the Nobel in 1923. Alexander Fleming, Ernst Chain and Howard Florey wouldn’t have discovered penicillin and its curative powers. Typhoid and yellow fever would still be raging across the land.

But Banting and McLeod’s methods with dogs, rabbits and fish probably would fail to pass muster with today’s regulating agencies. It’s not only federal regs that have changed — it’s the moral, philosophical and ethical sensibilities of Americans toward creatures of all kinds. Oregon State biomedical ethicist Courtney Campbell has seen a sea change over the past decade and a half.

"Nothing is more important in an animal study than the animal itself," says Steve Durkee.

“There’s a generational change going on,” says Campbell, who helped lead a series of national ethics workshops for land grant faculty in the 1990s. “The change isn’t limited to animal research at universities — it’s also about food and entertainment and sports. It’s about the treatment of animals at zoos, circuses, aquariums, rodeos. “It’s about our diets — how veganism and vegetarianism were way out in the ‘fringy granola movement’ not that long ago. “We haven’t done a complete cultural 180, but there is definitely a new moral consciousness.”

At the end of the day

In the rat room, the “Bruss” eaters live alongside the “brocc” eaters (broccoli sprouts) and the “fat” eaters (high lipids). There’s a control group, too, which eats regular rat chow. That’s so Dashwood can compare the health impacts of an ordinary diet against those of the special diets. At the study’s start, all the animals were injected with the carcinogen found in charred meat — a known cancer-causing compound to which most Americans have been exposed in barbequed burgers or grilled steaks. Once the study is over, the animals will be euthanized, humanely, in strict accordance with the protocols set out by the American Veterinary Medical Association. The researchers will then compare the number and size of colon tumors among the four groups to find out whether eating sprouts made a difference.

When they talk about ending the lives of animals used in biomedical research, Diggs, Durkee and Murray all express a resigned sadness. None of them could do their jobs without a total conviction that scientific discovery justifies the animals’ demise — that the death of a rat may someday save the life of a child. Still, it’s unsettling. “Nobody likes it,” muses Murray, his attempt at matter-of-factness not 100 percent convincing. “But it is what it is.”

Editor’s note: Read more about Oregon State’s leadership in animal ethics in the Winter 2013 Terra.

Helen Diggs has responsibility for the more than 600,000 research and teaching animals at Oregon State. (Photo: Frank Miller)

A human life can pivot on the quirkiest of convergences. In the life of Helen Diggs, it was the accidental nexus of five unfortunate hikers, a bagful of poisonous mushrooms and a few heroic pigs that set change in motion.

It all started early one morning in 1988 when Diggs, then a young veterinarian, heard an urgent knock at the door of the lab-animal surgery where she worked on Portland’s Pill Hill. “Doctors! Come quickly! We’ve got some patients who need livers!” The two physicians Diggs was prepping for animal surgery peeled off their latex gloves and dashed out.

The timing couldn’t have been more fortuitous for the poisoned hikers, who had eaten “death cap” mushrooms (Amanita phalloides) after mistaking them for the edible “paddy straw” species. Liver transplants were still rare in those days. But the two surgeons, one from Oregon Health & Science University and the other from the Oregon Veterans Administration, had spent the previous summer transplanting livers into research pigs with assistance from Diggs, who ran the animal O.R. So when four of the five hikers were raced to the hospital with critical organ failure, the surgeons were ready to perform the first human liver transplants ever done at OHSU.

All four patients survived. And Diggs had an epiphany.

“It was a really beautiful moment for all of us,” she recalls. “Most of the time in animal sciences, we’re working at the bottom of the research pyramid, trying to find answers at the level of basic discovery. It can seem remote from its eventual application in medicine. But this time, our work went straight to the operating room in a human hospital and saved four people’s lives. I thought, ‘Oh my gosh, we’re right at the pinnacle.’“

Life-Saving Connection

Still, she expected research to be a stopover on the way to a more “warm, fuzzy” practice. When she graduated from Oregon State’s College of Veterinary Medicine in 1985, she envisioned treating horses and cattle or, perhaps, cats and dogs. But with that urgent knock on the surgery door, the profound link between animal research and human health hit home. Her thinking began to shift.

“It makes you feel like a million bucks when you can be that close to a life-saving event,” says Diggs, OSU’s attending veterinarian for animal research.

Another convergence — this one involving lambs, preemies and high-tech blood-oxygenation pumps — clinched it for Diggs. She was pregnant with her first daughter when she and her animal techs at OHSU were testing new oxygen pumps on lambs to ensure that the life-saving machines could safely be hooked up to infants at the neonatal intensive-care unit at Portland’s Emanuel Hospital. The “lambs were just adorable, frolicking and trying to nurse on your finger,” she recalls. Having to euthanize the animals after the testing was “really hard” on the young vet. She questioned whether working with research animals was for her. Then one day while on maternity leave, she went to the hospital, her newborn bundled in her arms for a well-baby checkup. Still full of gratitude for the animal-tested technologies that had saved her own baby during a rough delivery, she bumped into a pediatric surgeon on the elevator. “Cute baby,” he remarked, abstractedly. “Oh, by the way, we’ve saved 60 preemies with that pump you helped us test.”

Her commitment to research was sealed.

Veterinary medicine wasn’t on Diggs’ radar as a girl growing up in Portland. Thanks to yet another unlikely collision of people, places and species (a village on the Chukchi Sea, a menagerie of arctic animals and scientists at a military outpost), she stumbled onto her calling in the early ‘80s. Fresh out of the University of Portland with a degree in education, Diggs landed a teaching job in Alaska. Finding herself isolated on the frigid North Slope, she filled the dark winter weekends by volunteering at the Naval Arctic Research Lab in Barrow, where veterinarians from the Lower 48 conducted thermal studies for the Department of Defense. The lab’s big predators (polar bears, wolves) and arctic birds (ptarmigans, snowy owls) grabbed her imagination. So did the science and the “friendly, embracing” spirit in the lab-animal community.

After a 25-year career that included top leadership posts at the University of California, Berkeley; the University of Texas Southwestern Medical Center; and the American College of Laboratory Animal Medicine, she came home to Oregon State in 2009. “Extraordinary” is how Rick Spinrad, vice president for research, characterizes her leadership and national reputation. Announcing her appointment in 2011 as head vet and director of the Laboratory Animal Resources Center, he noted the astounding array of species under her care, “from tadpoles to swine.”

"By standardizing and harmonizing how animals are cared for, you create consistency across labs and institutions," says Steve Durkee

“Nothing is more important in an animal study than the animal itself,” says Steve Durkee. His tone is reminiscent of Moses handing down the stone tablets. Just like Moses, Durkee is not kidding around.

The righteous idealism that fed Durkee’s Greenpeace activism in his “younger, wilder days” still beats in his chest as administrator of OSU’s Institutional Animal Care and Use Committee (IACUC) — a group of researchers, veterinarians, ethicists and laypeople who meet monthly to review each and every proposal for an animal-using project before it can go forward. His job is to make sure no animal is used needlessly, no animal suffers undue pain, no animal dies in vain.

“It’s not a light topic,” he says, sitting in his office amidst copies of Lab Animal magazine and photos of Murphy, his Goldendoodle. “Day in and day out, it’s a whole lot of seriousness. To me, these animals are heroes. They’re giving their life for the greater good.”

Heroes, perhaps, but not volunteers. The rats nibbling on Brussels sprouts for a colon-cancer study in the Linus Pauling Science Center didn’t choose to participate. And that, precisely, is why they need a surrogate. Durkee speaks for them. He puts himself in their shoes — rather, their paws: How would it feel to be one of those rats in Cage 57? Would he be stressed-out? Lonely? Would he be bored? Would he be too hot or too cold? Would he feel pain or anxiety?

The answers to these kinds of questions determine whether a research or teaching project gets an OK from the IACUC, which Durkee advises on regulations and national standards. Every iota of proper care — from lighting and companionship to noise, vibration, enrichment and surgical procedures — is detailed in the Guide for the Care and Use of Laboratory Animals published by the National Research Council of the National Academies. Moses had his stone tablets. Durkee has the eighth edition of the Guide.

“We have a really serious charge,” he says, “to evaluate whether the benefits from a project justify animal life or involvement.”

Care and Security

The benefits of animal research aren’t just theoretical for Durkee. When his mom was battling breast cancer, her treatments had been tested on animals. She didn’t survive the disease. But other women have beaten breast cancer thanks to the rats, mice and other creatures that participate in biomedical studies.

In return, Durkee says, humans have an obligation to feed, house and handle animals with the utmost care — even during dire emergencies. After a severe East Coast power outage cost nine rats’ lives at his previous workplace, the University of Michigan, he wrote a comprehensive disaster-planning outline for animal facilities to follow during hurricanes, blackouts and other disasters. Coincidentally, as he was making final edits, Hurricane Katrina struck New Orleans. So he found a very receptive audience when he presented his outline at a national animal-care conference barely two months later.

Last winter, when floods washed out roads and power lines in Benton and Lincoln counties, plans derived from his outline kicked in to protect fish and other sea life at OSU’s Hatfield Marine Science Center, as well as animals on campus. Because even when researchers are riding out the storm at home and staff are trapped by fallen trees or collapsed bridges, captive animals need food and fresh water, heating and cooling, bedding and medicine.

“Using animals is a privilege, not a right,” Durkee insists. “We owe them gratitude and respect.”

ALS Genetic and chemical interactions are being revealed in patients with Lou Gehrig’s disease. (Rats)

Fetal Developmen Cancer-fighting nutrients taken in pregnancy protect fetuses from carcinogens. (Mice)

Head and Neck Cancers These cancers contain a five-fold spike in the protein Ctip2, suggesting new tools for detection. (Mice)

Melanoma A protein called RXR-alpha in some skin cells can protect pigment cells from damage. (Mice)

Obesity A chemical in hops, xanthohumol, reduces body weight and lowers fasting plasma glucose. (Rats)

Parasitic Infection. A parasite called microsporidia, which can infect humans, can be transmitted via eggs. (Zebrafish)

Spinal Cord Injury Vitamin E given intravenously within four hours of spinal cord injury increases survival and recovery. (Rats)

Tooth Ename. Discovery of a tooth enamel-regulating protein could allow teeth to be grown in labs. (Mice)

Toxicology The chemical BPA, used in plastic food containers, causes neurobehavioral changes. (Zebrafish)

Tuberculosis Development of an oral therapy for TB and of an aerosol for treating bacterial lung diseases could lead to vaccines. (Mice)

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

Adrian Gombart

Deadly staph infections may have a potent new foe: Vitamin B3. Megadoses of the vitamin can help the immune system fight the superbug MRSA (methicillin resistant Staphylococcus aureus), researchers at Cedars-Sinai Medical Center, OSU’s Linus Pauling Institute and other institutions have found.

The findings could lead to new treatment options for health officials who have seen rates of bacterial skin infections spike in hospitals and nursing homes. In recent years, MRSA has made aggressive forays into the wider community as well, turning up in daycares, military barracks, gyms and other places where people have skin-to-skin contact.

“This is potentially very significant,” says Oregon State researcher Adrian Gombart. “Antibiotics are wonder drugs, but they face increasing problems with resistance by various types of bacteria, especially S. aureus.” However, Gombart warns against taking high doses of the vitamin, noting that the findings haven’t yet been tested in humans.

Wendy Baltzer

In 2008, Chewy (see Cut to the Bone) was one of almost 6,000 dogs and cats referred by veterinarians across the Pacific Northwest to OSU’s small-animal clinic and hospital, a leading institution not only in minimally invasive surgery but also in therapeutic laser research and treatments for cancer, cardiovascular disease and other illnesses.

After his surgery, Chewy participated in a double-blind study (meaning that nobody knows which patients are getting the therapy and which are getting a placebo) conducted by his surgeon Wendy Baltzer. She is administering low-level laser treatments to 12 subjects to test whether the technique speeds healing after surgery. Another recent study led her to invent a new method of Achilles tendon repair using a muscle flap as described in the March 2009 issue of Journal of Veterinary Surgery. And with a seed grant from the American Kennel Club Canine Health Foundation, she is currently looking into hormonal links to the growing incidence among dogs of cruciate ligament ruptures like the one that hobbled Chewy.

Baltzer’s career demonstrates the three-pronged mission of a land grant university. That’s because teaching, research and outreach are tightly bound into every aspect of her practice. It’s this tripartite opportunity — to mentor aspiring veterinarians, to investigate novel treatments and to heal cherished pets — that keeps Baltzer in academia when she could earn significantly more in private practice. She sums up her commitment this way: “You can’t help but love coming to work.”

Rachel Miller will head for Poligny, France, this summer to test ice-cream recipes. (Photo: Lee Sherman)

When Rachel Miller was shadowing a pie scientist in her hometown of Spokane, Washington, no one — not her teachers, not her parents, and certainly not she herself — could have predicted that her high school job shadow would lead to possibly the coolest summer internship in the universe: tasting ice cream in France.

OK, so let’s back up a minute. A pie scientist? Really? The year was 2008, and transfats were the newest boogeyman in the food industry. The scientist Miller shadowed at Cyrus O’Leary’s Pies was reformulating recipes, replacing shortening with healthier palm oil. Sugar, too, was on the food industry’s hit list as Americans’ waistlines swelled and their blood sugar spiked. Enter low-sugar pies and yet another reformulation.

Miller admits that her teenage choice of a job shadow had more to do with her sweet tooth than with any carefully thought-out career goal. Nonetheless, a career path began to unfold for this child of a meteorologist dad and a veterinarian mom (who worked with bomb-sniffing dogs during a military tour in Kuwait). After a senior-year visit to Oregon State University, Miller set her sights on the Department of Food Science and Technology. Studying food appealed to her practical nature.

“Food science is so applicable to everyday life,” she says. “It’s not one of those sciences where you have to work in a lab. Your kitchen can be your lab.”

A part-time freshman gig crunching data for OSU cheese researcher Lisbeth Goddik introduced Miller to the chemistry, microbiology and artistry of curds and whey. So a logical spot for her first summer internship was Oregon’s famous Tillamook Cheese Factory, where she chemically analyzed milk samples and inspected incoming ingredients like sugar and salt. The next summer, she worked at the Darigold plant back home in Spokane.

Finally, her professional life looped back to its origins: that sweet tooth. At the end of her senior year at OSU, Miller was accepted as a summer intern at ENILBIO, the National School of Dairy Industry and Biotechnology. Tucked away in the picturesque French town of Poligny, the school resides in one of the world’s finest cheese-making regions. The school also researches ice cream.

Miller’s delighted grin seems to say, “Can you believe it?” as she explains her summer job testing the texture of ice cream made without chemical emulsifiers — compounds like polysorbate 80, monoglycerides and diglycerides — that give ice cream its smoothness, free of gritty ice crystals.

“It’s all about mouth feel,” she says, sounding very much like a vintner after swishing, sipping and spitting a pinot noir. “Consumers want a creamy, pleasant mouthfeel, but they don’t want the substances that create that pleasant texture. It’s a Catch 22.”

In France, she’ll be looking at what happens to ice cream, texturally, without those multisyllabic emulsifiers. It’s all part of an international trend, Miller says. More and more, consumers avoid foods listing unpronounceable additives and unrecognizable terminology on their packages. “There’s a big push to clean up the labels on food products, to limit the number of ingredients and to use only natural ones,” she says.

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For more information about education abroad opportunities for OSU students, contact the International Degree & Education Abroad (IDEA) office at 541-737-3006.

Fistula survivors gathered with Bonnie Ruder at Terrewode shortly before her departure from Soroti in March. (Photo courtesy of Bonnie Ruder)

Bonnie Ruder, a midwife in Eugene and an Oregon State master’s student in public health and anthropology, had gone to Uganda to learn about a traumatic condition known as obstetric fistula. It arises when labor is prolonged and the constant pressure of the baby on the birth canal causes tissue to die and a hole to open between it and the colon or urethra. Globally, about 2 to 3 million women suffer with the condition and the heartbreaking social isolation it causes. In Uganda alone, about 140,000 women live their days unable to control persistent leakage of urine or fecal matter, and about 1,900 new cases arise there annually. (See Birth Knowledge, an October, 2011, Terra story about Ruder’s research.)

During her time in Uganda, Ruder worked in a regional hospital in the town of Soroti. She interviewed 17 fistula survivors in their homes and in the offices of Terrewode, a nearby women’s health organization. She wanted to know what they had experienced and how they understood the causes of fistula. This summer, she is analyzing the information for her master’s thesis in OSU’s Reproductive Health Lab, but her eventual goal is to assist Terrewode in educating and treating women and reducing the number of new cases.

“It was eye opening,” she says. “I heard their stories about trying to get to a hospital (to give birth), and once they got to the hospital, being ignored for days. They said that the doctors checked on them and just kept saying it wasn’t time. When it finally became ‘time,’ the baby could be dead, and they would rush the women into surgery. The women would be told their baby was dead, that there was nothing the doctor could do, and they would be sent home.”

It was common, Ruder adds, for a woman to be told nothing about what it meant to live with a fistula or how it could be treated. “Sometimes the health-care people would say ‘come back,’ but if she is really poor, how is she supposed to come back? In the meantime, her husband would leave her, and she would be pushed further into poverty to the point where she won’t be able to come back.”

Meanwhile, a potential source of help has been outlawed by the government, she adds. The majority of rural women still give birth at home with the help of a family member or traditional birth attendant. About 60 percent of Uganda’s births occur in this fashion, but in 2010, the government made birth attendants illegal. “They’re really trying to import the Western way of birth without the resources to do it. It doesn’t feel locally appropriate,” she says.

Policy Not Enforced

Fortunately for women who still rely on birth attendants, it’s a cosmetic policy, adds Ruder. Enforcement is nonexistent. Still, what little support birth attendants had received from non-profit organizations has declined, and women have a harder time getting access to attendants’ services.

At the same time, the hospital birthing system is badly overworked. So-called free beds are available, but to use them, patients must bring all their own food and supplies and have a relative or friend bring them any drugs they might need. To get timely help from a doctor or a midwife requires a “tip,” which is usually out of reach of the very poor.

While she was in Soroti, Ruder worked with Terrewode to identify women with fistulas and to get them treated. “If fistula victims can get to town, Terrewode will take them to the hospital and give them all the supplies they need and check on them daily. They’ll tip the doctor to move them up higher on the list of people in line for surgery. And when the surgery is done and women are ready to go home, they also give them bus fare,” says Ruder.

Although she returned to Oregon in March, Ruder continues to assist Terrewode by writing grant proposals. The group is educating a network of women who can promote sound birthing skills and identify fistula sufferers in need of help.

Oregon State’s relationship with Terrewode continued through the efforts of another master’s student in public health, Lauren Baur from Pennsylvania. In July, Baur followed in Ruder’s footsteps and went to Soroti to assist Terrewode. See a video about Baur’s experience below.

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For more information about education abroad opportunities for OSU students, contact the International Degree & Education Abroad (IDEA) office at 541-737-3006.

On a light box, an OSU researcher observes protein gels used in biochemical experiments. (Photo: Jan Sonnenmair)

It’s not a huge stretch to say a story like this is unfolding at Oregon State University. Against legions of bacteria and other microbes that cause TB, cholera, malaria and other infectious diseases, a cadre of OSU scientists has taken up arms. Their light sabers are machines called chromatographs and mass spectrometers. Their droids are “high-throughput” plate readers and underwater robots. Their curative elixirs derive from weird and remote organisms like gelatinous “sea squirts” from Africa’s Cape of Good Hope and giant tubeworms from the Axial Volcano a mile beneath the Pacific Ocean.

The story’s ending has yet to be written. But so far, the odds are with the germs. As Earth’s first inhabitants, bacteria have a 3-billion-year evolutionary jump on Homo sapiens. Superbly adept at adaptation, they’ve found genetic avenues into every ecological and biological niche, from polar icecaps to the human gut. They divide like crazy (some can double their population in nine minutes) and use an astounding array of strategies to make themselves at home. Many bacterial species do good things, like recycle waste. But other species, the ones scientists call pathogens, can invade and quickly overwhelm their host organisms, whether animal or plant. Miracle drugs like penicillin, once seen as impregnable shields against deadly infection, are losing their power as the bacteria regroup and recalibrate.

For all its brainpower and glittering technology, modern science is struggling to stay ahead of these microscopic shape shifters. The microbes have outmaneuvered just about every drug medical science has thrown at them.

This is the story of OSU’s heroic battle to outwit these cunning adversaries. From running high-speed experi- ments in Corvallis, to surveying patients at Portland’s Oregon Health & Science University (OHSU), to combing health-care data- bases for trends, the researchers are attacking infection and prevention from every conceivable angle. They search vast international databases for promising compounds. They decipher mechanisms for disease-promoting phenomena like bacterial sliming and swarming behaviors. They ponder unlikely-seeming disease pathways, such as those between pigs, fish and humans.

The eight professors in the colleges of Pharmacy, Science and Veterinary Medicine you will meet in these pages gather biweekly to trade insights and design collaborative investigations, ranging from microbes’ molecular structures to hospitals’ dosing protocols to urbanites’ risks for drug-resistant infections. Here we look in on their journey, from lab bench to sickbed to public square.

Deep Ocean Dive

Kerry McPhail reaches into a Styrofoam cooler and lifts out a jagged black rock the size of a cantaloupe. “We collected this from an active volcano on the bottom of the Pacific, a mile deep,” she says, her voice accented with the musical tones of southern Africa. Under her office’s fluorescent lights, the rock’s sharp facets shine like obsidian.

In their natural-products lab, Kerry McPhail (left) and Taifo Mahmud examine a flask containing an antibiotic-producing red marine cyanobacterium growing in modified seawater. The cyanobacterium produces different toxins depending on the composition of the seawater. (Photo: Jan Sonnenmair)

Her pride in this solidified chunk of deep-sea lava might suggest that McPhail is an Earth scientist. Why else would she join a 2009 NOAA expedition exploring the Axial Seamount 250 miles beyond Oregon’s shore? So it’s curious to learn that McPhail is neither a geologist nor an oceanographer, but a medicinal chemist in the OSU College of Pharmacy. Curious, too, is the fact that her research endeavors aboard the voyage were funded in part by the National Institutes of Health (NIH), along with Oregon Sea Grant.

What McPhail was seeking in those lightless depths, with the help of a diving robot named Jason II, was new sources of life-saving drugs. The black rock, grabbed by Jason II’s mechanical arm from inside the caldera, was coated with billions of protozoa that thrive on super-heated sulfurous waters at vent sites, where magma bubbles up from the subterranean. As unlikely as it seems, this bluish “microbial mat” may harbor healing chemical compounds never seen before. McPhail and her team have brought home other promising vent-dwelling extremophiles, as well, collected from giant tubeworms, “snow blowers” (white clouds of microorganisms spewing out in 200-degree plumes), orange-colored biofilms (slimy layers of swarming microbes). Some of her specimens were collected during the famous 2008 NOAA expedition when a never-before-witnessed eruption of the underwater volcano was caught on tape by OSU scientists.

“There’s an enormous diversity of microbes down there that people just had no idea about,” she says.

But the cold Pacific isn’t McPhail’s only odd-organism goldmine. Closer to Zimbabwe, where she spent her childhood on an agricultural research station and later in the capital city of Harare, she has been collecting and studying gelatinous creatures called tunicates. Known colloquially as “sea squirts,” these sac-like filter feeders are plentiful in the waters off South Africa. Having previously isolated potential anti-cancer compounds from tunicates, McPhail now has begun testing them for possible antibiotic properties. She also collaborates with OSU medicinal chemist Taifo Mahmud, who studies the curative powers of rare microbes living in the soils of “blackwater ecosystems” in the tangled jungles of Indonesia (see “Nature’s Medicine Chest,” Terra, Fall 2010).

Why are these strange and remote creatures so intriguing to McPhail? Why are deep-sea vent organisms significant enough for the NIH to award her one of its coveted “R21” grants for high-risk, exploratory projects? What makes tunicates worth the regular trips she makes to South Africa to collaborate with a fellow scientist at Rhodes University, where she got her Ph.D.?

It’s their very rarity that makes them promising in drug discovery.

“Unique organisms from unusual, diverse ecosystems have unusual chemistry,” says McPhail. “My lab is testing these organisms for unknown bioactive compounds — ones that target pathogens in unexpected ways. These compounds then can be used to design a new generation of drugs to fight infection.”

Tracing the chemical “fingerprints” of these novel compounds against known compounds catalogued in databases and examining microbial growth patterns in Petri dishes are the first steps in drug discovery. Next, McPhail will move on to studying disease progres- sion in animals. Once again, she’s eyeing a singular creature. This time, it’s the waxworm. Surprisingly, this caterpillar larva of the wax moth (a member of the “snout moth” family) has an immune system similar to that of mammals. That trait, along with being cheap and plentiful, makes the waxworm an excellent subject for drug discovery.

Nature of the Beast

In the global fight against infectious disease, new drugs are urgently needed. That’s because bacteria and other pathogens are evolving day-by-day, minute-by-minute, to withstand the onslaught of existing drugs. They survive by creating mutant versions of themselves or by swapping whole chunks of DNA with other microbes. Not only have pathogens learned to foil single drugs, they’re now fending off multiple drugs simultaneously. These multidrug-resistant germs have been dubbed “superbugs” in recognition of their ninja-like powers of intracellular infiltration and assassination.

A lab technician separates and analyzes DNA fragments isolated from a bacterium in an experiment to find natural-product biosynthetic genes. (Photo: Jan Sonnenmair)

“For every antibiotic that’s ever been used, resistance has developed,” says OSU researcher David Bearden.

“It’s a hard game to play, because the truth is, the more you use it, the less well it’s going to work. That’s just the nature of the beast.”

It’s that beast’s nature — elusive, mutable — that captures Bearden’s imagination as a clinician. Infectious agents, he says, are a lot like those moving targets in the carnival booth. By the time you get one in your sights, a new one has taken its place.

“It’s a foreign-invader scenario,“ explains Bearden, who chairs the Department of Pharmacy Practice. “You’re giving drugs to the person to kill the living organisms that are attacking them from inside. And all the while, the thing you’re fighting is changing.”

Just outside the window of his 12th-floor Portland office, the aerial tramcars connecting OHSU’s South Waterfront to Pill Hill creep up and down the forested slope like silver beetles. On the adjacent lot below, workers in hardhats are running cranes and positioning girders for the Collaborative Life Sciences Complex, a joint project of OHSU and the Oregon University System. Bearden and another dozen pharmacy researchers who work at the OSU Center for Health and Healing will join scientists and clinicians of OHSU and Portland State University in the new complex when it opens in 2014.

While McPhail and Mahmud are rummaging in some of nature’s most peculiar ecosystems for new drugs, Bearden is looking for better ways to use the drugs already available. Resistance gets a boost when too many people take too many antibiotics, he points out. Patients suffering from colds and flu may request — even demand — antibiotics from their doctors. But because those common ailments are caused not by bacteria but by viruses, taking antibacterial drugs is an exercise in futility. Adding to the problem, many patients take their prescriptions inappropriately or stockpile antibiotics for future use. Remnant germs may lurk in the organs or tissues of their human host, building strength for another assault.

To combat the misuse and overuse of antibiotics, Bearden is looking into optimizing dosages and calibrating them for special groups, such as the obese. “Substandard dosing — concentrations that fail to inhibit or kill all of the bacteria — can induce or enrich resistance,” says Bearden. “Say you have a population of 1 million bacteria, and maybe 1,000 of them are very resistant. If you kill off 999,000 of them, the rest of them have this nice, free niche to become the dominant population.”

From her office a few strides from Bearden’s, OSU epidemiologist Jessina McGregor elaborates: “Optimizing the choice of drug, the dosage, the duration of therapy and the route of therapy — whether oral, topical or intravenous — are the next steps in prudent antibiotic use after first cutting down on overuse. That’s the focus of a lot of pharmaceutical research on infectious disease.”

Bio-Bargain Hunter

When Aleksandra Sikora gets excited about a buy-one-get-one-free deal, it has nothing to do with the half- yearly sale at the mall. Rather, she does her bargain hunting in scientific supply catalogs, such as the dog- eared booklet from Greiner Bio-One that sits on her desk. By stretching dollars, the OSU microbiologist can run more experiments with the startup grants that currently fund her research on cholera (which sickens more than 300,000 yearly) and gonorrhea (the most prevalent infectious disease in the United States).

Aleksandra Sikora, along with her husband and research partner Ryszard Zielke, is investigating ways to combat the germs that cause cholera and gonorrhea. (Photo: Jan Sonnenmair)

Opening a cupboard in her level-2 bio-safety lab in OSU’s Pharmacy Building, Sikora takes out a crisp new package of clear-plastic trays, each about the size of a slice of bread.

“We use 20 to 30 of these sterile plates each time we run a screening for bioactivity,” says Sikora, who grew up in Gdansk, Poland, and has a Ph.D. from the University of Gdansk. “They’re expensive, about $3 to $4 each. If you buy them from Greiner Bio-One, you get one free for every two you order.”

What she’s after in those screenings are “hits” — that is, signs of bioactivity. A bioactive agent or compound is one that affects a living organism such as the gonorrhea-causing bacterium Neisseria gonorrhoaeae or the cholera-causing bacterium Vibrio cholerae, Sikora’s current subjects of study. A hit can show up as a faint glow (“bioluminescence”), which some microbes emit as they send chemical signals back and forth. It can also show up in patterns or rates of bacterial growth. Lack of growth, too, can tell a story.

If she gets a hit, she can see it almost instantly on a computer screen. Thanks to her pricey plastic trays and an even-pricier BioTek plate reader she ordered for her lab soon after arriving at OSU last fall after her post-doctoral training at the University of Michigan Medical School, the whole process is automated. She can run nearly 3,000 tests in just minutes using the high-speed robotic machine, which purrs with perfect precision. That’s because each plate contains 96 “wells” — little troughs that hold samples of bacteria inoculated with whatever compounds are being tested — and the plate reader holds up to 30 plates. Scientists call this type of ultra-fast screening “high-throughput” — in other words, putting samples through chemical and biological analyses at accelerated rates (compared to the old days, when researchers had to run them manually, one at a time).

The gleaming stainless-steel gear gracing Sikora’s lab will let OSU’s team of infectious-disease researchers create their own electronic “compound library.” To that end, Sikora is testing bioactive compounds from McPhail’s vent organisms and sea squirts and Mahmud’s blackwater bacteria, along with her own experiments.

Sikora’s target in the infectious-disease battle is the microbe’s cell wall — the point of contact between the pathogen and the host. It’s where virulence gets a toehold. Instead of targeting the whole cell with a drug designed to kill it outright, Sikora and Ryszard Zielke, her husband and research partner, hope to block “virulence factors,” the actions of bacteria that cause disease. Toxins and other proteins secreted from the cell wall, as well as the composition of the wall itself, are of particular interest.

Chatty Bacteria

In the pantheon of weird sea creatures, the Hawaiian bobtail squid ranks near the top. This 2-inch “stealth bomber of the ocean,” as Natural History magazine calls it, is worthy of Dr. Seuss’s imaginary bestiary. This tiny nocturnal squid even has a biological buddy, a bacterium called Vibrio fischeri that dwells inside a sort of built-in lampshade on the belly of the eight-legged cephalopod. The squid nourishes the dense bacterial populace, which repay the favor by glowing just enough to cancel out the squid’s silhouette as it swims, rendering it invisible to predators. “Interestingly,” OSU microbiologist Martin Schuster notes, “the bacteria don’t glow when they’re out in the open ocean by themselves.”

How do these one-celled wonders accomplish this stunning feat of variable bioluminescence? As biologists discovered in the 1970s, they do it by sending chemical signals back and forth. These bacteria essentially talk to each other in a process called “quorum sensing,” a stunning discovery that led to a paradigm-shift in microbiology: the realization that microbes aren’t loners but rather social creatures that communicate and cooperate with each other.

“Microbes talk,” says Schuster. “And we’re listening in.”

The discovery of quorum sensing in Vibrio fischeri, a microbe beneficial to its host, set off a flurry of new findings. Cell-to-cell communication, it turns out, is common in disease-causing bacteria, too. This includes Pseudomonas aeruginosa, the primary organism under study in Schuster’s laboratory. This notoriously antibiotic-resistant bacterium causes serious hospital-acquired infections and is the main cause of death among people suffering from cystic fibrosis.

Schuster is studying how germ-to-germ dialog fosters disease-causing actions among bacteria, such as secreting harmful toxins or enzymes that break down host tissue. Biofilm formation, a gabfest among millions of microbes, is another. These “cities of microbes” can be up to 1,000-fold more resistant to antibiotic treatment than free-floating bacteria and are the source of many chronic infections. They build a slimy coating that shields the germs deepest within the biofilm. They draw strength from their surrounding compatriots.

“Biofilms and nasty toxins that harm the host are produced by bacteria as a group,” Schuster says. “It’s a concerted effort.”

What Schuster hears as he eavesdrops on these secret chemical conversations constitutes a novel approach in antibiotic design: disarming rather than killing the pathogen with so-called anti-virulence drugs. “With traditional antibiotics, you basically wipe everybody out,” says Schuster. “Only the resistant clone remains and then just explodes.”

Scientists generally assume that if bacteria aren’t threatened with annihilation, they won’t work so hard to create new versions of themselves. Minus this “selective pressure” — evolution’s relentless push for genetic adaptation to environmental threats — resistance won’t develop. This assumption had never been tested experimentally, until now.

What would happen, Schuster wondered, if he shut off the bacterial chatter? Could he halt the behaviors that bolster the disease process? Could he slow the evolution of resistance, the looming problem with traditional antibiotics? The answer to both turned out to be yes. Graduate student Brett Mellbye ran a number of “evolution-in-a-test-tube” experiments, mingling drug-resistant bacteria with non-resistant bacteria. The non-resistant bacteria, Mellbye discovered, got ahead by “cheating” — that is, by exploiting the nutrients and other resources supplied by the resistant bacteria. The cheating put the brakes on resistance.

“The suppression of resistance is contingent on the targeting of cooperative behaviors,” Schuster cautions. The next step in verifying these findings is to move the experiments from test tubes to animal models.

Fishy Germ Swap

How could an Atlantic whitefish caught off Boston pass a germ to a pig on an Iowa hog farm that winds up infecting a teenager in Seattle? It hasn’t happened yet, as far as we know. The pathway from fish to hog to human is not a straight line; it zigs and it zags. But OSU veterinary microbiologist Dan Rockey says it’s just a matter of time before all the dots connect.

The reason: Antibiotic overuse isn’t limited to hospitals and doctors’ offices. Factory farms and feedlots, which routinely give antibiotics to healthy livestock to promote growth and prevent disease, can become breeding grounds for resistant germs. As a rule, pigs and cows don’t pass those dangerous germs to people. That’s because bacterial species rarely jump from animals to humans, or vice versa. For instance, chlamydia, the disease Rockey studies, is common across the animal kingdom, yet each animal has its own version of the germ. “A single chlamydia species generally dials in to a single animal species,” he explains. “The organisms that infect a koala bear or a horse or a lizard or a frog — those don’t cross over.”

But as we know, bacteria everywhere are hardwired to adapt — even on an Iowa pig farm. That’s where Rockey and some colleagues from Iowa State and the University of Washington recently discovered a strain of bacteria resistant to tetracycline, the most common antibiotic used to treat humans suffering from chlamydia (a range of diseases affecting eyes and sexual organs). The researchers traced the microbe to the pigs’ diet: fishmeal. It appears that a complex DNA switcheroo among fish pathogens created a genetic perfect storm for tetracycline resistance.

“One fish pathogen had all the right genes coded in the right sequence,” he says. “Lo and behold, crazy but true, this other fish pathogen, unrelated to the first pathogen, has a complimentary set of genes. Somehow, the two fish pathogens got together and then got into the chlamydia that infects pigs, which often are fed fish waste, especially in the Midwest. This story tells you how complicated it is for antibiotic resistance to spread between humans and animals.”

So far, chlamydia in humans remains treatable with tetracycline and other antibiotics. But Rockey’s research suggests that a day will come when the human chlamydia germs C. trachomatis and C. pneumoniae join the ranks of resistant germs. In his lab, Rockey was able to engineer a tetracycline-resistant human chlamydia strain using DNA from the resistant pig strain. If science can do it in the lab, nature can do it in the wild — and sooner or later, it will.

“If tet-resistance were to get into the human strain, it could spread around pretty quickly,” Rockey says. “Tetracycline is a primary drug of choice against chlamydia infections. This could really be a problem, especially in developing countries.”

Evidence is mounting that animal-human crossover can and does occur. Rockey cites a significant paper by the Phoenix-based nonprofit TGen (Translational Genomics Research Institute) describing how the creation of methicillin-resistant Staphylococcus aureus (MRSA) likely was generated by contacts among humans, pigs, bacteria and antibiotics. Here’s what the study found: Pigs acquired a strain of S. aureus from humans, a strain that initially was treatable by antibiotics. But because pig farms are awash in antibiotics, the strain quickly developed resistance inside the pigs. Today’s MRSA problem may well have originated with the next step in that chain of infection: the bacterium’s jump back to humans, this time in its resistant form.

Lance Price, the TGen study’s lead author, sounded a warning. “Our findings underscore the potential public health risks of widespread antibiotic use in food animal production,” he said in announcing the study results in February. “Staph thrives in crowded and unsanitary conditions. Add antibiotics to that, and you’re going to create a public health problem.”

Skin-to-Skin Contact

Factory farms and feedlots aren’t the only “crowded and unsanitary conditions” that promote staph infections. Gyms, dorms, barracks, playgrounds, day-care centers — close quarters where people have skin-to-skin contact — are a growing worry in health-care circles. In most cases, S. aureus, is usually a harmless hitchhiker on healthy human skin. But sometimes it invades its host, often through a cut or abrasion. The boils, carbuncles, pimples, yellow crusts and milky pus associated with staph infections, while unsavory, are usually treatable. However, adding MRSA strains to this mix leads to “more and more stubborn infections at which doctors throw more and more drugs,” Rockey says. Sometimes, patients fail to respond. Sometimes, they die.

This trend gives a sense of urgency to researchers like Jessina McGregor, an OSU microbiology graduate who came back to join the faculty after getting her Ph.D. from the University of Maryland School of Medicine. Like David Bearden, her colleague down the hall, McGregor is captivated by bacteria’s warp-speed knack for adaptation.

“You can actually observe evolution happening!” She leans forward in her chair, the energy in her voice rising as she contemplates the awesome power of microbial communities. “You can directly observe the bacteria’s response to evolutionary pressure. With larger organisms, you would have to watch for decades or millennia to witness evolutionary change.”

As an epidemiologist, McGregor scans, not populations of microbes in Petri dishes, but populations of humans in all sorts of settings — cities and states, hospitals and doctors’ offices, residential-care facilities and outpatient clinics. She studies long-term data and looks for trends. She plumbs the numbers to stem the threat of resistant disease.

One solution is outreach. Hand-in-hand with the Oregon Department of Health, she and OSU pharmacy students have spearheaded a local project under the national AWARE (Alliance Working for Antibiotic Resistance Education) umbrella, which fans out across the state with brochures, games, videos and face-to-face conversations for local communities. Other solutions may emerge from her current studies of urinary-tract infection patterns at Kaiser Permanente Northwest and OHSU, as well as infection rates among inpatient-versus-outpatient settings.

So far, McGregor says, Oregon and Portland have dodged the full force of resistance hammering other states and cities. “What’s happening in Oregon is very different than in other places in the U.S.,” she explains. “We have very different prescribing patterns here. Oregon is one of the lowest antibiotic utilizers per capita, behind only Alaska. That definitely helps us out.

“Having locally specific information to guide our policies is important. We don’t need to be reactionary ahead of the curve.”

Now More Than Ever

Ironically, the escalating demand for new drugs coincides with declining dollars for antibiotic research. That’s because pharmaceutical companies are concentrating on “blockbuster” medicines for patients with long-term conditions, like elevated cholesterol and high blood pressure. Antibiotics don’t pencil out on the balance sheet, say six sponsors of a bipartisan bill currently before Congress.

“The development of any new pharmaceutical costs hundreds of millions of dollars for basic and clinical research,” write the sponsors, three Democrats and three Republicans from six states. “For antibiotics, revenue is limited because they tend to be prescribed for short-course therapies that are completed in days or weeks.” If it passes, the GAIN Act (Generating Antibiotic Incentives Now) will create incentives to encourage R&D and speed up drug discovery.

The bill’s sponsors mince no scary words, spare no sobering statistics. “The antibiotic pipeline is dwindling, and a global crisis looms,” they write. “Each year, antibiotic-resistant infections are responsible for tens of thousands of deaths, hundreds of thousands of hospitalizations and up to $26 billion in extra costs to the U.S. health-care system. Just when we need innovation the most, the pipeline of drugs to replace ineffective antibiotics has dwindled to a trickle.”

To turn that trickle into a life-giving river, infectious-disease research at OSU and other universities is more urgent than ever. Taifo Mahmud sums it up simply: “We are running out of drugs. We have no other choice than to keep moving.”

After all, a hero perseveres, no matter the cost, no matter the odds.

Illustration by Teresa Hall

It’s one of life’s little ironies. The proteins in our bodies fight infection, carry messages, ferry oxygen and build tissue. But then, like double agents in a spy novel, they can betray us. They overreact to a virus and attack our own organs. They promote cancer, help clog arteries or set up roadblocks in the brain. We may never know until symptoms appear — a lump, chest pain, severe memory lapses — and irreversible damage is done.

Who wouldn’t like to get ahead of these heart-stopping scenarios? By detecting proteins gone awry or elevated in the earliest stages of disease, scientists are opening up the possibility of effective therapy before health is compromised. The standard checklist on the annual physical — temperature, blood pressure, reflexes, lung function, skin condition — is already backed up by blood tests for molecular markers such as cholesterol and other proteins. What researchers envision is an inexpensive (some aim for a “penny per protein”), accurate and rapid test that can be performed in a doctor’s office and provide unprecedented views of our biochemistry on the fly.

In medical research labs across the country, a race is on to identify new biomarkers and to develop highly sensitive technologies that can measure them. Talk about a needle in a haystack. A single blood sample can contain roughly 9,000 types of proteins, although different analytical techniques produce widely varying estimates. And on top of the sheer flood of proteins is the fact that they are shape shifters. Once released into the bloodstream, they may be altered before they reach their intended destination.

Oregon State University chemist Vince Remcho likens the search for proteins to fishing. “Ultimately you are searching for one particular protein or other molecule in a vast soup of molecules, so you have to choose the right bait. My group is in the bait business, bait and hook,” he says.

In Remcho’s lab in OSU’s new Linus Pauling Science Center, some of that bait consists of short relatives of DNA known as aptamers. If the team of students and other researchers has prepared their devices properly, they will attract big fish, proteins and other molecules that fit into the nooks and crannies of a particular aptamer and no other. Remcho and his international team (hailing from Indonesia, China, Nigeria, Thailand and the United States) develop new tools — lab-on-a-chip technologies, microfluidics and nanosensors — for scientific, medical and precision manufacturing purposes. But their goals can’t be achieved by chemistry alone, so at OSU, they rely on the expertise of physicists, engineers and molecular biologists to advance sensing science.

Marked Molecules

Knowing how to catch proteins is one thing. Knowing which proteins to catch is another. The U.S. Food and Drug Administration now recognizes nine biomarkers for use in clinical diagnosis of cancer, and researchers have identified others that serve as markers for kidney and liver disease, Alzheimer’s, rheumatoid arthritis, tuberculosis and other illnesses. “There are new markers coming out everyday from different labs,” says Arup Indra in the OSU College of Pharmacy.

The Indra lab is one of them. In 2009, he, Gitali Indra and collaborators at OSU and in France reported a new biomarker for head and neck cancers. With funding from the National Institutes of Health, they conclusively linked a protein known as CTIP2 to squamous cell carcinoma. Squamous cells are flat, plate-like cells in the skin and the lining of internal organs. When it occurs in the head and neck, squamous cell carcinoma is the sixth most common form of cancer worldwide — promoted by exposure to tobacco, alcohol and human papillomavirus.

It is aggressive and hard to treat. Despite advances in chemotherapy and surgery, five-year survival rates have not improved over the past 20 years. And until the CTIP2 discovery, researchers had had limited success in identifying biomarkers for use in clinical oncology.

In December 2011, the Indras and their colleagues Mark Leid of OSU and French biochemist Joseph Abecassis received a United States patent for the use of CTIP2 in cancer diagnostic tests. “Cells that are dividing rapidly express more CTIP2,” says Arup Indra. “It is a marker of cell proliferation. We don’t know for sure if it is a cause of cancer, but we suspect strongly that it is.” The protein has also been called a “master regulator” because it influences cell development in skin, teeth, the brain and immune system.

In storage tanks cooled by liquid nitrogen, the Indras maintain some human oral-cancer cell lines that overproduce CTIP2. With partners at OSU and the Oregon Health & Science University in Portland, Gitali Indra leads studies on its role in the development of normal tissues as well as cancer. “CTIP2 is expressed in normal cells but at much lower levels,” she says.

Personal Proteomics

“A higher-than-normal level (of CTIP2) indicates that an individual could be at risk,” adds Arup. “If you are getting more than a normal detectable level, you could determine that she requires monitoring.”

The Indras’ work with cell lines is just the beginning. Before CTIP2 becomes useful in the doctor’s office, its function needs to be studied in animals and then human subjects. “We need to understand how disease progresses in animal models, how levels of a given biomarker are changing,” says Arup.

Moreover, no protein acts alone. Each operates in a network. So the ideal biosensor will be capable of monitoring many proteins at once. The hope is that such devices will enable every person to have a composite protein profile, a biochemical fingerprint, for evaluating health as we age.

Researchers will need better technology to reach that goal. While the Indras can analyze CTIP2 and other proteins through existing laboratory techniques, their efforts bump up against detection limits. A better way to fish for proteins would enable them to pick out one molecule among thousands and to see small but possibly significant trends. Just as the Indras identify biomarkers and the Remcho lab develops ways to catch them, Ethan Minot is working on a new type of fishing line for CTIP2 — a more sensitive detection system made of carbon nanotubes.

Planting Nanotubes

These slender threads of pure carbon are hollow and so tiny that they are invisible to the naked eye, even under the most powerful light microscope. And they bring a valuable benefit to protein detection: They conduct electricity with such sensitivity that physicists can measure the tiny change in electric current that occurs when a single molecule lands on their surface. That makes them good candidates for the kind of detection system needed by the Indras and other molecular biologists. However, despite their size, making and developing a nanotube-based detection system is no small matter.

Ethan Minot and his team use light to analyze the structure of carbon nanotubes grown in the lab. (Photo: Jan Sonnenmair)

With support from the Oregon Nanoscience and Microtechnologies Institute (ONAMI) and OSU start-up funds, Minot has established a lab in the OSU Department of Physics for studying nanotubes and graphene (one-atom thick carbon sheets). He and his team sow nanotube “seeds” — catalysts that sequester carbon atoms from gases such as methane and ethylene — onto a silicon chip. At about 900 degrees Centigrade, carbon nanotubes grow in only a few minutes.

But it can take hours of painstaking work to determine exactly what kind of tubes the researchers have made. “When you bind carbon atoms together into the nanotube structure, there are at least 100 different ways to do it. So the diameter can be different and every one has slightly different properties,” says Minot. Carbon bonds also take a variety of angles as they grow. These so-called chiral angles affect the way a nanotube conducts electricity and binds to other molecules.

Fortunately, physicists have more than a few tricks up their sleeves. After they remove the chip from the furnace, they load it into a machine that has become standard in labs that manipulate matter at this scale: the atomic force microscope. The device can “see” structures smaller than the wavelength of visible light. Its fine-tipped needle creeps slowly across a surface and deflects ever so slightly when it comes close to a nanotube. The resulting map — mountains, valleys and objects on the molecular landscape — reveals the location and length of every nanotube on the surface.

But researchers aren’t done. It takes another step — analysis of each nanotube by lasers tuned to precise frequencies — to determine the angle of the carbon bonds, which is key to the nanotube’s electrical properties. Working with the Remcho and Indra labs, Minot and his team are developing ways to bind small molecules — the bait — to nanotubes and then detect biomarkers such as CTIP2 — the fish — in a simple saline solution.

Something that has so far eluded the Minot lab’s grasp is the successful detection of a protein in a blood sample. “If you have a mixture that you’re sensing, like real blood, there are thousands of different types of proteins. Most of them you want to bounce right off the sensor. One out of a thousand (proteins) has the right chemical structure to stick to it. That’s the ideal situation,” he adds. “Sensors will pick up anything unless you treat the surface correctly.”

Out of the Lab

Members of Minot’s and Remcho’s labs and a colleague at UC Santa Barbara reported in January 2012 that they had succeeded in nearly tripling the speed of a prototype detection system. Their advance stemmed from preventing proteins from sticking to other surfaces in the system.

“To increase detection speed, we relied a lot on surface treatments that can stop proteins from sticking where they shouldn’t,” says Minot. “Our next step is to make specific proteins stick to the nanotube. There’s an element on the nanotube that will click onto an element on the aptamers (the bait for catching proteins). We prepare the nanotube in a reactive state and the aptamers with reactive ‘handles’ and wait for them to find each other.”

While refining biosensor chemistry is hard enough, the electronics present another major hurdle. “If anything stops this from being commercialized from the electronics point of view,” Minot adds, “it’s the fact that if you wait a half hour, there are slow changes in baseline resistance. When we do an experiment, it might last five minutes, and we bind proteins onto the surface in that amount of time. We see a very clear signal over that period of time.

“But commercial devices don’t have the same luxury as a research experiment. They don’t have a grad student, who knows exactly what’s going on, watching over it. Can this thing be automated, take the human interpretation out of it? That’s a big challenge.”

Meanwhile, Oregon businesses are expressing interest in OSU’s developing technologies. Minot is working with Voxtel in Beaverton on methods for controlling nanotube properties in manufacturing. And a company known as mAbDx Inc., a spinoff from the University of Oregon, has taken an option on an antibody to CTIP2 based on work by the Indras and Leid.

Not Just Nanotubes

Nanotubes are just one of the technologies in development. Other approaches at OSU include magnetized “nanobeads,” the focus in Pallavi Dhagat’s lab in the School of Electrical Engineering and Computer Science. Working with Remcho’s group, Dhagat has developed a way to turn ferromagnetic iron oxide nanoparticles, extraordinarily tiny pieces of rust, into sensors. Such particles not only can detect chemicals with sensitivity and selectivity, but they can be incorporated into a system of integrated circuits to instantly display the findings. The applications could extend to homeland security and environmental monitoring as well as to medical diagnostics.

Meanwhile, the search for faster, affordable, sensitive and accurate diagnostic tools is ongoing. At Caltech researchers have proposed a multi-protein testing method in which a blood sample is washed across a chip. They generate a mosaic of colors, each one associated with a different protein. A Boston University group is measuring changes in light waves propagating across a metallic surface designed to bind proteins.

“It doesn’t have to be nanotubes,” says Minot. “Maybe somebody else is going to get it. But there’s a lot of excitement that we’re moving this way. Someone is going to nail it.” And when they do, the proteins that betray us will have nowhere to hide.

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Feb. 22, 2013, scientists at the University of Pennsylvania report a nanotube-based technique for early detection of prostate cancer.

This is bad news for women, who are more prone to “metabolic syndrome” — a cluster of risk factors including so-called “stubborn belly fat” often targeted in diet ads. Exercise is one of the best ways to prevent or shed extra tummy pounds along with twin health worries high cholesterol and high blood pressure. But that’s not all. Exercise also can boost mood and buoy optimism, say the study’s authors Bradley Cardinal of OSU and former OSU student Paul Loprinzi, now at Bellarmine University in Kentucky.

“Those who get at least 30 minutes of exercise a day are less likely to be depressed, less likely to have high cholesterol and less likely to have metabolic syndrome,” the researchers conclude.

Exercise habits start in childhood. But even for adults, it’s never too late to change. Pressed for time? Solutions can be as simple as spurning the elevator and climbing the stairs. Even pacing while talking on the phone can enhance your health, the researchers say.

“You set the example as a parent in your own emotions and reactions,” says researcher Shannon Lipscomb at OSU-Cascades. “Parents’ ability to regulate themselves and to remain firm, confident and not over-react is a key way they can help their children to modify their behavior.” Genetics, however, does play a role, Lipscomb and her colleagues found. Children may remain at risk for negative emotionality as an inheritance from their birth parents, despite being raised in low-stress adoptive homes.

• Jon Furuno, College of Pharmacy, studies the incidence and severity of MRSA in hospitals and long-term care facilities.
• Margaret Dolcini, Department of Public Health, studies the behaviors and attitudes of urban African-American youth at risk of HIV/AIDS. Her goal is better prevention strategies.
• David Williams, Linus Pauling Institute and Department of Environmental and Molecular Toxicology, focuses on the interaction between genes and drug effectiveness in anti-malarial treatments. He aims to maximize drug effectiveness and minimize toxicity.