Seeing the right research opportunities

Two weeks after finishing veterinary school in her native South Africa, Caroline Zeiss, PhD, a diplomate of two prestigious professional societies in veterinary and animal medicine, arrived in the United States with one suitcase. Thirty years later, she is a professor of comparative medicine and of ophthalmology and visual science, and chief of pathology in comparative medicine. Her journey to Yale by way of the University of Pennsylvania and Cornell University involved determination, perseverance, and, as she said, “a lot of serendipity.”

While her doctoral work at Cornell piqued her interest in her specialty of translational research, Zeiss’ position at Yale was “completely decided by fate.” After finishing her PhD, Zeiss was once again left with a two-week window, this time until her visa expired. By a stroke of luck, a job at Yale was available. “It really was the best fit that it could have been,” said Zeiss. “Intellectually the environment is really amazing. There are so many areas that you could choose to grow your research into. There is also a very strong clinical laboratory animal medicine program.”

Zeiss’ own research asks an important question: Why do so many promising animal studies fail to translate to human treatment? One reason is complexity. “We use animals to model aspects of human disease that are vastly simplified in the animal model. Most human diseases are very complex because we live a long time and have a lot of exposures. In animals, we remove some of those variables, and then you have a pure system that you can test a hypothesis on. And that gives you answers. It allows you to understand mechanisms. But the downside is that when you try and translate that back up to people, the results you get in animals often fall apart.”

Complexity is not something Zeiss shies away from; in fact, she’s attracted to it. Fascinated with the central nervous system, Zeiss focuses her studies on Alzheimer’s and Parkinson’s diseases. “Not only are they prevalent, they cause a great deal of suffering, and they are very complex,” she said. As a veterinarian, Zeiss is concerned about animal health in her research. “Using animals is a privilege,” she said. “If you’re going to use them, you have to do so in such a way that really informs human health. If you’re doing translational research, it’s important to design studies with outcomes that are important to patients in mind.”

This design may mean considering alternative approaches, and also evaluating work that has already been done to identify biases in study design that impede translation to human medicine. To help that process, Zeiss designed software that harvests animal and human data from PubMed across the entire field of Parkinson’s disease over the last 70 years. In this spirit of learning from and working with other scientists, Zeiss would love to see greater commitment to collaborative research in academia. Instead of a publish-or-perish culture that rewards the number of papers or grants that an individual has, Zeiss wishes there were investment in cross-disciplinary groups, specifically for people who haven’t been strongly funded or who don’t have a long track record. “If we were more collaborative and that was the basis for promotion and retention, I think everything would benefit: science would benefit, faculty would benefit.”

Among researchers, Zeiss has seen a shift to collaboration during the COVID-19 pandemic. “Everybody in the research community wants to help,” she said. “It’s such a crisis that a lot of people have shifted their research to focus on this.” Zeiss’ own team is currently doing two studies: one looks at a native rat virus with transmission characteristics similar to those of COVID-19, using it to inform statistical models to predict when the disease will reach a steady or endemic state in the population; and one looking at the interaction of COVID-19 and influenza in hamsters to predict what impact the annual flu season will have on the current pandemic.

Zeiss is positive about the changes she’s seen in society over her lifetime. “Things change suddenly. I think we’re in a period now where significant progress will occur,” she said, in reference to recent calls for social justice. Though she recognizes that structural evolution takes time, Zeiss knows it is possible. Having left South Africa before apartheid ended, she has witnessed improvements each year she’s gone back to visit. And Zeiss, who identifies as LGBTQ, has seen progress in that realm, too. In South Africa, which she describes as very conservative, Zeiss was not out. When she interviewed for her position at Yale, she was open about her LGBTQ status. Now there is federal recognition regarding marriage and workplace discrimination, though “only recently (2015 and 2020),” she notes.

Zeiss became a United States citizen in 2006 and feels deeply patriotic. “I’m very much invested in helping people understand how immigrants shape this country,” she said. In 30 years, Zeiss’ own positive contributions have been acknowledged across many disciplines.