Human Developmental Biology Resource (HDBR): an embryonic and fetal tissue bank for functional genetics and cell-based research

Birth defects occur in 3% of pregnancies and are responsible for 20% of infant deaths. They include conditions like spina bifida, hole-in-the-heart, and cleft lip and palate which pose often life-long medical problems for the child, caring challenges for the family, and a considerable financial burden for the health service. While pregnancy termination can be an option, the ultimate goal is to learn how birth defects develop in the embryo and fetus, so that preventive measures can be offered. These might involve vital nutrients like folic acid, or stem cell transplants which hold great promise for future disease treatment. In addition, many rare diseases of both children and adults first arise owing to a problem during development of the fetus before birth. Researchers are increasingly finding faulty genes to be associated with such diseases, raising the possibility that genetic counselling and perhaps gene therapy might be offered in future. However, we need to understand how such genes function in the embryo and fetus, in order to move forward towards new methods of diagnosis and treatment. While research in animals can help in providing information on the origin of such diseases, there is ultimately no alternative to studying the processes in humans themselves. The Human Developmental Biology Resource (HDBR) enables this vital research by providing scientists with access to material from human embryos and fetuses. The HDBR has ethical and Human Tissue Authority approval to collect, store and distribute human fetal material for research. The material is obtained, with informed consent after the woman has received professional counselling and decided to terminate the pregnancy. The samples are examined for stage of development and their chromosomes are tested to determine if they are normal. The tissues are then either sent to researchers for immediate preparation of cell cultures or biological molecules, or else the samples are frozen or otherwise preserved for later distribution to researchers. Sample details are recorded on a secure database that is anonymized, so no link to the donating women exists in the data. HDBR staff also carry out research work on the human material, on behalf of scientists, where this is required. To date, over 400 different research projects have received material from the HDBR, and this has led to over 200 scientific papers being published. Discoveries have included genes that interact to cause Hirschsprung's disease (absent nerves in the bowel), an improved understanding of genes contributing to schizophrenia and the identification of genes for severe eye defects. In this way, scientists are using HDBR material to learn how genes contribute to human development and how mutations (mistakes) in these genes may lead to birth defects or rare diseases. In the present proposal, the HDBR seeks further funding to pursue and extend its service to the international scientific community. New developments will include: (i) a focus on extending the collection to later fetal stages, as required for studies of human brain development; (ii) a new systematic collection of fetal material from pregnancies being terminated because of prenatally diagnosed birth defects, thereby allowing research into these diseases; (iii) expanding the tissue preparations that HDBR provides to researchers, to include material suitable for studies of the genetics of single cells, which is now becoming technically possible; (iv) the provision of 'hotel' facilities in our laboratories to enable researchers to be trained in best use of HDBR material; (v) a new linkage of data from genetics studies with our existing gene expression database (Human Developmental Studies Network; HuDSeN) which will for the first time allow scientists to observe how individual genes are expressed in the human embryo/fetus in relation to all the active genes and proteins that are present in that tissue or at that stage of development.