The field of genomics is rapidly expanding. Whilst clinical medicine has yielded limited benefit from this technology to date, we are entering an era where genomics will be as vital to any medical student’s education as anatomy and physiology currently are.
With a radical reduction in cost, outstripping Moore’s Law, patients are increasingly having their genome characterised either through recruitment in clinical trials or via direct-to-consumer genetic testing. Throughout medical school, genetics is usually considered a challenging subject and many leading clinician-scientists are concerned that the next generation of clinicians will struggle to provide care for patients requiring a genomically driven management plan.
We currently stand at the cusp of translating a wealth of actionable genomic data into improved patient outcomes; a significant limitation relates to how we can efficiently determine disease-causing mutations. I aim to deliver a brief overview of how genomics is beginning to be integrated within clinical medicine and hope to encourage you to engage with these advancements.
Disease has been traditionally classified based on the anatomical or physiological hallmarks of an observed process. Genomics is allowing us to molecularly define pathology, categorise disease pathophysiology with higher resolution and accept that multiple causative mutations may contribute towards a single phenotype.
Partitioning patients based on their specific genetic mutations is an attractive option. This strategy has been employed within cancer, a purely genetic disease, and has allowed delivery of specific therapeutic agents to attenuate disease processes (metastatic melanoma and BRAF V600 inhibitors). Many more common diseases are now being re-defined. This philosophy has created new branches of therapeutics, those that are genomically guided. Two drugs highlighting the success of this approach are Ivacaftor and Eteplirsen for rare single-gene diseases, Cystic Fibrosis and Duchenne Muscular Dystrophy respectively. In addition, gene therapy- whereby a defective gene is replaced with a functional copy – is also emerging as a feasible therapeutic option following the approval of Glybera for lipoprotein lipase deficiency. Whilst these drugs have been developed based on sequence variants, the recent efforts of the ENCODE study- which described all functional elements of the genome- deliver additional information for drug developers to explore.
Knowledge of an individual’s genome will also encourage more logical usage of pre-existing therapeutic agents. Current practice employs population based medicine theory where everybody receives the same drug, at the same dose for a single condition, despite us knowing that we are fundamentally different at a molecular level. This strategy has demonstrated great success but can be further improved. Taking into consideration an individual’s genotype, drugs with known side effects or reduced efficacy can be avoided. Examples include simvastatin and skeletal myopathy, flucloxacillin and hepatotoxicity and carbamazepine and Stevens’ Johnson Syndrome. Further information on this has been summarised in this recent review article.
Drug re-positioning strategies have also shown success with improved knowledge of the genome. Libraries of therapeutic agents are being assessed for their suitability to treat other diseases, in addition to their currently licensed conditions, based on their molecular function. This approach has shown considerable success for Rapamycin, an immunosuppressant used to prevent rejection in organ transplantation, in patients with Progeria.
Other benefits to incorporating genomics within clinical medicine relate to screening. Prenatal screening has been revolutionised by sequencing fetal DNA extracted from the mothers’ blood, reducing the risks associated with amniocentesis or chorionic villus sampling. Also, tracking infectious disease outbreaks and characterising the microbiome are areas where genomics has ameliorated previous technologies.
As medical students we are pluripotent and undifferentiated as regards our potential speciality. Genomics is delivering a wealth of information and as potential care providers it is necessary that we understand our responsibility to utilise genomics within any specialty we may decide to take.
About Andrew Harper:
Andrew Harper is a New England Journal of Medicine Scholar. He is a final year medical student at Newcastle University in the United Kingdom and has gained an MSc in Medical Genetics with distinction. His current clinical interest is structural heart disease, but he also has research and teaching interests. He has published a wide-range of research articles, his most recent featuring in Nature Biotechnology. You can follow Andrew on twitter (@arharper17) to find out more about genomics and digital health.