By Rachael Warecki ’08
As the world becomes increasingly globalized and virus transmission occurs more easily across continents, medical research scientists are focusing on treatments that provide positive health outcomes for the greatest number of people. In true liberal arts tradition, three Scripps chemists—a professor, a student, and an alumna—are using their research to make medications safer, advocate for more inclusive clinical trials, and improve conditions for humankind.
Science in the Social Sphere
Associate Professor of Chemistry Anna Wenzel
When she’s not in the classroom, Associate Professor of Chemistry Anna Wenzel can often be found with members of the Chemistry Club, advancing scientific knowledge in the Claremont community and beyond. Since Wenzel founded the club during her first year at Scripps, its projects have included environmental soil analysis with local elementary school students, volunteering at the Southern California Science Olympiad championships, and a Scripps-Pitzer Science Center cookbook that is raising funds for the humanitarian-focused organization Chemists Without Borders.
A current collaboration with Chemists Without Borders involves the chemical analysis of pharmaceutical samples to evaluate suspect medications collected by research partners in Kenya, Uganda, Tanzania, India, Nepal, and Malawi. This spring, courtesy of a Keck Foundation donation, Wenzel acquired a mass spectrometry instrument capable of this level of chemical analysis, enabling students in her natural science courses to participate.
This kind of community engagement—what she calls “science in the social sphere”—is one of Wenzel’s core principles. Bringing science out of the lab and demonstrating its real-world applications, whether by performing a chemical analysis of the College’s olive oil or showing high school students how to make liquid-nitrogen ice cream, is key to battling the public’s growing mistrust of scientific research.
“There are a lot of really big policy decisions that involve some fundamental understanding of science. People need to be able to trust their scientists—and they don’t trust people they don’t know,” she says. “Going out into the community really breaks down that mistrust and allows people to be more open-minded about scientific discovery.”
For this reason, non-major chemistry courses are Wenzel’s favorites to teach, since they give her another opportunity to introduce non-scientists to chemistry’s practical applications. Her students learn about the “bench to bedside” process, through which lab research at the cellular level (the “bench”) is converted into human drugs and therapeutics (“bedside”). This process includes creating safety nets that prevent dangerous drug interactions, as well as taking steps to boost a medication’s efficacy and reduce its toxicity.
Wenzel also wants her students to understand the current and historical shortfalls of drug discovery. Women and people of color frequently aren’t part of clinical trials, despite their different metabolisms and enzyme functions, but the recommended dosages on the sides of prescription bottles are still one-size-fits-all. The recommended dosage for a man, for example, could lead to a very different outcome for a woman. Wenzel hopes that this knowledge will help students better navigate and advocate for their own medical care.
Tuberculosis Treatment for the 21st Century
Kara Dunne-Dombrink ’20
Tuberculosis, commonly known as TB, is often depicted as a 19th-century illness in Western popular culture. But in many developing nations, it’s still a major cause of death, according to the World Health Organization’s list of 30 countries with a high burden of the disease. If left untreated, TB can be fatal to almost half of those affected—but the recent emergence of drug-resistant strains has made TB treatment even more difficult.
Kara Dunne-Dombrink ’20, a dual major in biochemistry and French studies, is exploring the development of an enzyme-based medication that could combat drug-resistant tuberculosis. Dunne-Dombrink is conducting this research under principal investigators Mary Hatcher-Skeers, professor of chemistry and Sidney J. Weinberg Jr. Chair in Natural Science, and Bethany Caulkins, visiting assistant professor of chemistry, with funding from the Weinberg Foundation. The bacteria that causes the disease needs tryptophan—that amino acid that makes you feel sleepy after eating turkey—to survive. By targeting and inhibiting the enzyme that creates tryptophan, scientists can kill the tuberculosis bacteria. Dunne-Dombrink hopes this approach, which replicates a reaction that already occurs naturally in the body, could lead to more effective
“We’re now in an age when so many diseases are more resistant to the usual medications, so finding new ways to treat new strains is really important,” she says. “We need to design drugs that are more similar to the body’s natural processes and reactions.”
In addition to the disease’s resistance to traditional therapies, the creation, testing, and administration of existing TB medication has also proven challenging. Dunne-Dombrink says it’s easy to get caught up in the minutiae of laboratory work and think of science as an isolated discipline. But medical research can often overlook the populations that would most benefit from drug discovery during clinical trials, resulting in treatments that are often expensive, with dosages designed for a narrow demographic. Dunne-Dombrink credits an anthropology class on Latinx workers in the garment industry with making her aware of the need for a more human-centered approach to scientific research. In examining the ways in which oppressive systems are interrelated, she realized that clinical research often reinforces other systems of inequality—and that scientists must think about
how their work connects to the rest of society.
“A lot of scientific research hasn’t benefited everyone equally,” she says. “We need to start thinking more holistically about how scientists can catalyze change across all communities and minimize harm to our environment and bodies.”
With a “big disease” like tuberculosis, for which antibiotics have existed for years, that means finding a treatment that is low-cost, environmentally green, and less likely to have adverse side effects, such as vomiting, jaundice, fever, and bleeding. Moving from a synthetic drug model to a more natural therapeutic that causes enzyme inhibition could help create such a treatment. Eliminating the expenses associated with synthetic creation would also lessen the medication’s cost.
However, this new treatment model comes with potential trade-offs. More natural, less carcinogenic medications are better for the body in the long term, but they may not be as efficient at treating the disease in the short term. These trade-offs are some of the issues she hopes to study further at the National Institutes of Health, where Dunne-Dombrink will be working in disease treatment next year.
“Science is about sharing your results with the wider world,” she says. “Thinking about the actual people this research might affect makes it valuable to more than just the scientific community. It places the science in the context of the real world.”
Chemistry with a Conscience
Claire Knezevic ’08
Claire Knezevic ’08 is the director of critical care laboratories and an assistant professor of pathology at Johns Hopkins Medicine. As a clinical chemist, she oversees the areas of the hospital laboratory in which chemical tests are performed on patient samples, such as electrolyte and cholesterol levels in blood and urine. Because she works in health care, particularly with medical test results, she regularly considers the impacts and implications of scientific research on patients. She calls a clinician’s ability to accurately perform these tests and report the results “the bread and butter of a clinical chemist’s job.”
“When faced with complex situations, my liberal arts education taught me how to hold back my own preconceived notions and embrace challenging viewpoints,” she says. “I think my education gave me the confidence to push myself in areas where I’m not strong, so that I can be more comprehensive in my understanding of my work.”
Knezevic has focused on research that she believes will benefit the most people from the widest variety of populations, such as drug discovery and the improvement of clinical practice. She also participates in collaborative translational research, which translates scientific discoveries into practices that directly benefit human health. Knezevic’s current research supports clinical trials for new formulations of pre-exposure prophylaxis, more commonly known as PrEP, an HIV-prevention drug. Existing PrEP medications require patients to take a once-daily pill. It’s a dosage routine that isn’t easy for everyone to maintain, Knezevic explains, but missed pills can lower the drug’s effectiveness. The new formulations she’s helping to develop—such as implants, injectables, and rings similar to hormonal birth control methods—would allow more people to choose the formulation that works best for them and improve the medication’s efficacy rate.
There’s no guarantee that Knezevic’s small slice of scientific research will have any long-term effect on human health—especially when 80 to 90 percent of a person’s health outcomes are based on social determinants such as race, class, and neighborhood of origin. That’s why Knezevic also works to create a more equitable society outside the lab. She volunteers with the Fair Development Roundtable to change the housing landscape in Baltimore, a city impacted by decades of red lining, disinvestment, and damaging real estate speculation. Her volunteer work is one of the reasons she chose to stay at Johns Hopkins after completing her fellowship.