演讲主题：

Genomics and the transformation of the clinical, chemical and pharmaceutical sciences

摘要：
Genomics can be defined as the use of molecular methods to interrogate the genome, the complete genetic make-up of a cell, individual or population (meta-genome). Over recent years, genomic insights have led to major progress in the clinical, chemical and pharmaceutical sciences that is reminiscent of the revolutionary progress made in those sciences at the end of the 18th century, accelerating over the first half of the last century and culminating in the establishment of the double-helical structure of DNA.

The DNA double-helix may perhaps be regarded as the demarcation symbol for the transition from the first revolution to the second. From that discovery has developed the bioengineering techniques that have led to the first recombinant therapeutic proteins such as insulin, and the biopharmaceutical industry. Replacement enzymes to treat deficiency diseases caused by genetic mutations soon followed.

With recognition that cancer was essentially a genetic disease, emerged targeted therapy and evidence-based preventive strategies (e.g. BRCA1 cancer risk variants). Identification of gain-of-function driver mutations and specific gene over-expressions led to paradigm-changing drugs such as imatinib and trastuzumab. Cancer is a hard disease to cure. Better understanding of how the cancer cell develops resistance and evades the host’s immunosurveillance has led to novel approaches for managing disease recurrence or relapse.

Similarly, improved genomic understanding has improved the management of other diseases including diabetes and recalcitrant infections due to multidrug resistant micro-organisms and various viruses. Genomic approaches are also providing highly informative insights that can inform the development and management of neurodegenerative diseases such as Parkinson disease and Alzheimer’s disease.

Diseases are no longer defined solely using clinical criteria. Instead, increasingly accurate and precise molecular sub-classifications are being made to allow stratification and personalisation of therapy. For example, breast cancer and lung cancer are no longer single diseases but groups of diseases that can be molecularly dissected and therapeutically targeted. Therapies are not only directed at the expressed proteins (e.g. enzyme inhibitors and monoclonal antibodies) but also at the encoding gene (e.g. gene therapy and exon skipping) and the RNA transcripts (e.g. antisense therapies and RNA-directed nucleases).

Genomic therapies are not for the future. They are already in the clinic and the range of such therapies is increasing rapidly. In this presentation we illustrate these broad-ranging applications of genomics with concrete examples and exemplars of interventions used in current practice.