The scientist studying how fugitive fetal cells may affect maternal health

Chimeras — fantastical creatures composed of different animal parts —  have appeared across cultures representing the wondrous, the grotesque, and the inherent complexity of identity. In ancient Greece, the chimera was part lion, part goat, part serpent. In classical Japanese history, it was made up of a monkey, tiger, and dog. Now, modern biology holds that humans can also be chimeras, housing cells from different genetic origins.

Kristine Chua, a postdoctoral researcher in biology at the University of California Santa Barbra, studies one form of chimerism — microchimerism — that occurs when cells are exchanged between mother and fetus during pregnancy. Her work has the potential to help reinvent how scientists define the human body as well as open new paths for understanding and improving maternal health.

As part of a group of researchers developing more sophisticated tools for studying microchimerism, Chua is also advancing the practice of biological anthropology, a science that has struggled with diversity and ethical approaches for studying humans.

“[Microchimerism] is still such a small field that there’s challenges in terms of work flows, gathering data, and recruitment,” said Chua, who was recently named one of STAT’s 2023 Wunderkinds. On the other hand, she said, “it’s very exciting because there’s an opportunity to ask questions that haven’t been answered or to open up spaces for other folks to evolve our thinking.”

For decades, scientists have suspected that cells from developing offspring can escape the uterus and travel through the bloodstream into mothers’ bodies, ultimately settling in their brain, heart, lungs, and other organs. However, researchers have only recently begun to explore how these fetal cells may affect maternal health, from potential benefits — faster wound healing and greater resistance to cancer — to downsides, like increased susceptibility to autoimmune disorders.

One of the difficulties of this newly burgeoning science is the rarity of fetal cells in mothers’ bodies, which range from 1 in 100,000 during pregnancy before declining to as few as 1 in a million after birth.

According to Sing Sing Way, a professor and researcher at Cincinnati Children’s Medical Center, the lack of tools and labs studying microchimerism has prevented the field from garnering the appreciation it deserves. “It’s foundational to how we define what cells are in our body,” he said. “We’re taught in high school that all the cells in our body are encoded by our DNA…and [having exceptions to that] would fundamentally change how our bodies work.”

Historically, scientists have studied microchimerism in mothers with sons, using the Y sex chromosome, which is only present in males, to distinguish between maternal and fetal cells. In a 2015 study, for example, pathologists examining the bodies of 26 women who had died during or just after pregnancy, found cells with Y chromosomes in every organ surveyed including hearts, brain, and kidneys.

Chua, who is a key part of an international research team — known as the Microchimerism, Human Health, and Evolution Project — is using more precise genetic markers capable of detecting differences in genes related to the immune system, which vary widely between mothers and fetuses of either sex.

In collaboration with local hospitals and expecting mothers donating blood samples, Chua is exploring how microchimerism varies across pregnant people as well as how this variation may impact the health of the mother and baby. One hypothesis is that the maternal immune system, which may be triggered by and in turn attack fetal cells, plays a role in determining the amount of microchimerism within the parent. Going a step further, Chua also plans to study the role of stress and socio-cultural factors that can modulate immune activity and thereby shift the balance of maternal and fetal cells in the mother’s body.

“Kristine’s taking a project that’s quite complex and even adding another really important layer  by putting it into the context of social human work,” said Amy Boddy, an associate professor of anthropology at the University of California, Santa Barbara, who leads the laboratory that Chua works in.

According to Boddy, taking into account how social-cultural circumstances affect biology is crucial because humans are social animals. This type of effect cannot be seen in a petri dish or database, and is an important component of research that is now gaining attention.

“You don’t find a lot of people out there who can really speak to both sides, when it comes to biology and the cultural determinants of certain factors,” said Boddy, “Kristine is right on the cutting edge of the field because she has expertise in both.”

Chua began navigating cultural and social dynamics long before she became a scientist. As a second-generation Chinese Filipina-American, she was raised in Los Angeles and nearby Rancho Cucamonga. In grade school, Chua’s teachers asked her parents to stop speaking Filipino in the home, so that she would learn English more quickly.

“It was fine at the time,” she said, “but by not speaking Filipino in the household and speaking only straight English, the language was lost.”

With her mixed heritage, Chua recalls occasionally feeling culturally adrift among friends who would claim that her way of doing things was not properly Filipina or Chinese. “I don’t know if it was an identity crisis,” said Chua, “but I would think, ‘Huh, this is really strange.’”

When Chua began studying anthropology in graduate school at the University of California, Los Angeles, the field was grappling with questions of identity and power dynamics that resonated with her own personal experiences. In particular, anthropologists were acknowledging the ethical complexities of extracting data from communities that were often less wealthy and more vulnerable than the Western countries where most studies originated from.

“I’m not saying that only people who are part of that community should do [anthropological] research, because then we wouldn’t get anything done,” said Chua. “But it’s more important to acknowledge your background, your positionality, where you come from, and how that can influence the questions you ask and some of the interpretations.”

For Chua, who had launched a pilot study in 2018 in the Philippines on how stress from an authoritative political regime might be transmitted from pregnant women to their unborn children, this meant rethinking her relationship to being Filipina as well as considering how best to connect with local hospital staff and study participants.

A key step in this process was relearning the language and cultural norms, and engaging study participants on a personal level. For example, while gathering hair specimens to measure long-term cortisol levels during pregnancy, Chua found that some women, who believed that cutting their hair during pregnancy would cause the rest of their hair to fall out, were reluctant to donate samples. The discovery “was important to keep in mind when designing future studies that called for hair samples,” she said.

Chua also bonded with a woman who was in labor for four days and kept returning to the hospital. “By the second or third day we were essentially friends,” said Chua. “She would ask where I was from, and compare and contrast cultural differences between the United States and the Philippines.”

Chua’s field work changed how she views her multicultural heritage. “Growing up, it wasn’t cool to be Asian … so I tried really hard to be more American,” she said. “But it was important to realize that there’s much more to me than just being American.”

Chua hopes this kind of approach will inform new standards in science.

“In terms of biological anthropology, there hasn’t been a lot of community engagement traditionally,” said Chua, who co-founded a DEI group as a graduate student at UCLA. “But there’s a push now to have better ethical practices, to do more than just dropping in, doing your study, leaving, and never coming back to the community you work with.”

For Chua, community engagement has included advising her Filipino research collaborators on how to set up new lab equipment for their own studies, as well as working with expecting mothers to improve maternal mental health studies.

Talking to pregnant women in the Philippines about their experiences “got me thinking a lot about how there is no universal definition of stress” and the complexity of approaching mental health issues in populations that don’t really talk about it, said Chua. Addressing mental health disparities in the U.S., she explained, may require using different language that helps people across diverse backgrounds better express what they’re feeling. “I think we need to be asking about mental health, but the way they ask in hospitals and in the U.S. medical system, they are probably not asking in a way that would make folks feel comfortable talking about it.”

According to Abigail Bigham, Chua’s graduate school advisor and associate professor of anthropology at UCLA, listening to communities and helping them articulate their needs and research interests is a critical component of human studies.“Kristine is a perfect example of someone thinking about the lives of the communities that she’s working with and how she can contribute to the ways in which they’re conceptualizing how they would like their well-being to improve.”

In Bigham’s experience, anthropologists and biologists are slowly changing their attitudes on studying humans. Instead of seeing people as passive study subjects, researchers regard them as active participants who can help shape the project and contribute key insights.

It’s an approach that Chua continues to hone in her current explorations of microchimerism and plans to incorporate in future studies. “We’re not there yet. We’re still at this point where we are trying to make changes,” said Chua, “But it is starting, and that is really exciting.”