Project Summary/Abstract
Genomic medicine and U.S. healthcare have reached an inflection point, where the next wave of innovative
technologies may alleviate or exacerbate existing health inequity. There are multiple ethical, legal and social
implications (ELSI) of transitioning from precision diagnosis to preventive treatments for genetic disease in a
societal context of significant scientific uncertainty and inequitable healthcare access. The implementation and
ELSI research oversight of fetal gene therapy – until now a hypothetical exercise – will profoundly shape
whether the NHGRI 2030 strategic vision for improved community stakeholder engagements and equitable
genomic medicine can be realized. The proposed K99/R00 Award presents a significant opportunity to
incorporate ELSI knowledge into the pioneering processes of fetal gene therapy by investigating three distinct
levels of ethical concern for emergent fetal gene therapy: clinical, regulatory and societal. Through
interdisciplinary training, mentorship, and collaborations with the University of California, San Francisco Center
for Maternal-Fetal Precision Medicine (CMFPM), the Stanford Center for Biomedical Ethics (SCBE) and the
UCSF-Stanford Center of Excellence in Regulatory Science and Innovation (CERSI), this project pursues an
ethnographic and “embedded ethics” approach to fetal gene therapy at a critical juncture in preventive
precision medicine and ELSI research. This multi-sited study on the ELSI of fetal gene therapy will connect
what happens in the clinic, and its regulatory infrastructures, with the larger-scale societal values that will need
to be incorporated to achieve greater social inclusion. The proposed five-year training and research program
prepares the candidate for independent ELSI scholarship in the field of preventive genomic medicine, by
harnessing ethnographic skills to complement a K99 acquired education in human genetics and genomics,
bioethics and community engagement methods. Three barriers to social inclusion are identified: 1) tensions
between clinical and social utility; 2) a lack of empirical data on decision-making processes given uncertainty;
and 3) equitable stakeholder engagements. These problems inform three specific aims of this proposal: 1) to
describe the processes that inform decisions about fetal gene therapy and its ‘utility,’ according to clinicians
and patients who are directly involved in the most promising fetal gene and molecular therapies at CMFPM
(K99); 2) to document how uncertainty is managed in the clinic and explore how this is shaped by social values
and socioeconomic supports (K99); and 3) to account for diverse, non-patient community views and the extent
to which fetal gene therapy developments are or are not socially inclusive (R00). Education and research to
fulfill these aims will advance understanding about the scientific, regulatory, clinical, patient, and societal
values that drive fetal gene therapy innovations. With unique ethnographic access to the clinical frontier of fetal
gene therapy, it will provide an understanding of the importance of social inclusion during the process of
knowledge translation, decision-making, and value-making.
