"Fundamental science requires time. And trust"

Prof. Dr Claudia Spits is a research professor at the VUB and affiliated with the Genetics Reproduction and Development (GRAD) research group. Her research is situated at the intersection of embryology, genetics and stem cell biology. One major question is central to her work: how does a human being develop in the first days after fertilisation, and which genetic factors control that process — or cause it to go awry?

To study this early stage of development, her team works with pluripotent stem cells, cells that can develop into virtually any type of body cell. “You can compare them to blank building blocks,” says Spits. “By monitoring how these cells behave, we learn how development normally proceeds and where it sometimes goes wrong.” The group also uses embryo-like models, carefully constructed cell structures that mimic certain characteristics of early embryos. These models allow researchers to study processes that are ethically and practically difficult to observe directly in humans.

The questions Spits is investigating cannot be answered quickly. “Development is not an on-off switch,” she says. “Small differences in the very early days can have major consequences later on.” That is precisely why the Methusalem funding from the Flemish government is so important for her work. This long-term support not only provides researchers with resources, but above all with the space to develop a broader research vision.

“You're not tied to a single, clearly defined project,” says Spits. “You can invest in people, infrastructure and ideas that are risky but potentially very innovative. That is only possible if you know you will be given time.”

The Methusalem programme, which she now heads, builds on a long tradition at the VUB. The research line was originally established by Professor Inge Liebaers and later expanded by Professor Karen Sermon. After the most recent evaluation, it came to Spits. “I stand on the shoulders of giants,” she says. “But I also see it as a responsibility: you must not only continue that line of research, but also innovate.”

A concrete example of what this long-term vision makes possible is her team's research into mitochondrial genetics in the context of fertility treatments. Mitochondria are the power stations of our cells and have their own DNA. For a long time, it was assumed that small genetic variations in them were insignificant as long as they did not cause disease.

“We hypothesised that even mild variations could influence early development,” says Spits. “But that idea was initially considered too speculative.” Thanks to Methusalem funding, the team was able to pursue this line of inquiry. The research led to a publication in Nature Communications and helped explain a clinical observation that had been known for some time: children born after fertility treatments have a slightly lower average birth weight.

“The effect is small,” Spits qualifies, “but it is important that we understand where it comes from. This shifts the discussion from ‘we see a difference’ to ‘we understand why’.”

In addition to fundamental research, her group also works closely with clinical practice, including on the genetic causes of infertility and developmental failure. “Not every study immediately leads to a treatment,” says Spits. “But sometimes we can make a diagnosis. And for many people, that is already very valuable. Understanding can bring peace of mind.”

Research into early human development inevitably raises ethical questions. According to Spits, Belgium has a strong and clear framework in this area, in which the VUB played an important role. “When I came to Belgium from Spain in the early 2000s, I was struck by how openly and carefully people deal with this subject here,” she says. “That is not a brake on research, but a prerequisite for quality.”

At the same time, the subject is emotionally charged. “When you work with fertility and children, you quickly realise that this is not abstract science,” she says. She also experienced this personally. “The mitochondrial research started shortly after the birth of my first child. And while that project was ongoing, we were ourselves considering whether we wanted a second child.” That combination made her extra aware of the responsibility that researchers and clinicians bear. “Science rarely provides simple yes-or-no answers. People make decisions in an emotionally complex context.”

Looking ahead, Spits sees a field of research that is rapidly accelerating. New techniques make it possible to study human biology with increasing precision, even outside the body. For example, her team works with organoids: miniature versions of human tissues that are grown in the laboratory and mimic certain functions of real organs. In combination with single-cell analyses — techniques that allow individual cells to be studied separately — researchers are gaining an unprecedentedly detailed picture of what happens during development.

"But we also encounter limitations," Spits qualifies. “Cells do not function in isolation. In the body, cells constantly influence each other and respond to their environment. We can never fully replicate that entire interaction in a dish. That complexity forces us to remain cautious in our conclusions.”

What keeps her going is the idea that development is not a fixed, linear process, but a dynamic form of evolution. “We often think in terms of one fixed genome per person,” she says, “but that’s not entirely accurate. Genetic diversity arises within a single individual at a very early stage.” Small changes during cell division can cause cells to differ slightly from each other genetically, with possible consequences for development and health later in life.

“Actually", she says with a smile, "I’m still doing what fascinated me as a student: studying evolution. Only not in species or populations, but within developing human tissues.”

If she could give young researchers one piece of advice, it would be this: let go of perfectionism. “Find something that really interests you and try to be good at it,” she says. “Excellence is not the same as perfection. Perfectionism is the enemy of progress — and of happiness.”