PhD defence S.A.L (Sietske) van Till

Below is a brief summary of the dissertation:

Sietske van Till has investigated the ethics of stem cell research for children with neurodevelopmental disorders. This research was part of the BRAINmodel project: a collaboration between various Dutch universities and academic hospitals, in which research is conducted into rare neurodevelopmental disorders caused by DNA mutations. These neurodevelopmental disorders are associated with a wide range of symptoms and have various manifestations. It can often take a long time before a diagnosis is made and appropriate care becomes available. New knowledge and technologies are advancing the development of new treatment options and are enabling researchers within BRAINmodel to better study rare neurodevelopmental disorders using patient-derived neuronal models. In her dissertation, Sietske van Till examines the ethics of this research: how can research be conducted responsibly, in a way that children and parents truly benefit from research?

First, an interview study was conducted with parents of children and adolescents with Kleefstra Syndrome or an STXBP1 gene mutation (two rare neurodevelopmental disorders) to gain more insight into parents' experiences, concerns, and expectations. Many parents felt they were "always switched on": they were constantly occupied with caring for their child and everything which comes with that, such as searching for suitable care and information about the condition, balancing caregiving tasks with other aspects of life (work, their own wellbeing, care for siblings), and coping with the emotional impacts of their child's condition. These results show that a broad approach is needed to support these families, including social, emotional, financial, and practical support for the entire family.

In addition, the research examined the moral value of neuronal models derived from human cells. Existing literature focuses mainly on concerns about whether complex neuronal models, specifically brain organoids, can develop consciousness. This dissertation shows that other types of value are also important for ethical guidance for research with less complex neuronal models, including the relational, instrumental, and symbolic value. These results emphasize that there are relevant considerations that are often overlooked, including the genetic link between neuronal models and their donors (who give informed consent for their use in research), the models' ability to mimic the (dys)functions of the donor's brain, and the models' contribution to meaningful research. It also warns against misleading communication about these models, such as incorrectly attributing human characteristics to neuronal models, as this can raise unnecessary ethical concerns and lead to a decrease in support for research projects using neuronal models.

The dissertation also describes parents' perspectives on research with neuronal models. Parents regard patient-derived neuronal models as valuable tools that can contribute to developing knowledge about disease mechanisms and, hopefully, ultimately to the development of new treatments. However, parents were also concerned about the burdens and risks of research participation for their child. Parents were especially cautious when it came to potential future research into experimental treatments: they feared medical risks, but also that a treatment could change their child's identity.

These various research activities show that a five ethical themes are important in responsible stem cell research for children with neurodevelopmental disorders: Beneficence (particularly promoting knowledge and therapeutic innovation), Risks of harm and burden minimization, Adequate governance of data and donated biological material, Informed consent, and Normative reflection on the use of neuronal models (BRAIN).

This dissertation highlights the need to actively involve parents of children with neurodevelopmental disorders in research projects. Our findings demonstrate that children should not be reduced to essentially their condition, but should be recognized as persons in their entirety, embedded in a social context. It is essential that information about neurodevelopmental disorders reflects the diversity of family experiences and includes both their challenges and positive dimensions. Moreover, it underscores the importance of promoting research that contributes to serving the needs of families, for example by promoting the development of medical treatments and other strategies that support the children’s development and overall well-being.