Keeping Genetics Human
Since my appointment as a clinical geneticist in 1984 in a department of Human Genetics I have been intrigued by the adjective “human”. The completion of the Human Genome Project was perceived by many within and outside our community as a turning point. The assumption is that the rich vein of “gene hunting” partnerships between clinicians and basic scientists will end and research institutes such as ours must diversify or perish. In practice, the ease with which a gene of major effect and its associated pathway can be linked to a defined phenotype has enriched that traditional interaction. Examples from our own institute’s work include the discovery of light chain ferritin as a basis for neuroferritinopathy and the identification of the delangin gene based on de Lange syndrome.
Most diseases include monogenic forms “lost” in a common phenotype. The disentanglement of the role of mismatch repair in colorectal cancer based on families with Lynch syndrome are an example. Such expansion of genetic medicine and development of tools to allow more effective complex trait analysis is a growing challenge, not least in developmental genetics where the question of what it is to be human takes on its sharpest focus. We are pursuing this in heart defects with mathematical approaches, vertebrate models and the establishment of the capacity to build 3D models using normal embryos.
We have extended into embryonic stem cell development and carried out the first human nuclear transfer. This has taken us into the broader issue of what it is to be human and our central role in defending the study of genetic control in cells capable of becoming separate individuals. Stem cell research holds great promise in treating genetic disease and is a legitimate direction of travel. The communication skills developed in the genetic clinic are critical in presenting such challenging research, as they will be as high throughput techniques take genetics into new domains such as near patient testing and preconception profiling.
Geneticists’ ability to learn from people with genetically determined disease while helping to defend their autonomy in the face of powerful technology provides a continuing reason to keep Genetics Human.