Development of genomic technology

In recent years, significant progress in the elucidation of the pathophysiology and aetiology of gastrointestinal disorders has been made. Novel experimental therapies which specifically target single steps in disease relevant regulatory pathways have been designed and are in different stages of clinical development. Examples are inhibition of the gastric proton pump in peptic ulcer disease1 and anti-tumour necrosis factor α therapy which has been developed for Crohn's disease and rheumatoid arthritis.2-4 This process was made possible by technological advances in cell biology, biochemistry, and microbiology and their application to disorders of the gastrointestinal tract. While this methodological approach has produced substantial advances in our understanding of gastrointestinal pathophysiology and increased available treatment options, there are currently several new challenges that call for the development of novel research techniques.

(i)

The pursuit of hypothesis driven functional research limits the scope of discovery to known genes and pathways and may therefore hamper the elucidation of novel genes and regulatory mechanisms.

(ii)

Exploration of signalling cascades and their role in disease pathophysiology has reached an enormous degree of complexity. Therefore, distinction between primary and secondary events is impossible in most cases. Even the exact mechanisms of a successful therapeutic application of targeted immune therapies (for example, therapy of Crohn's disease with tumour necrosis factor binding monoclonal antibodies) are not completely clear.5,6 Application of exploratory techniques based on a hypothesis free approach using high throughput (“parallel”) methodologies may help to establish a hierarchy of known and new players in signalling pathways and to identify key events in the mechanism of anti-inflammatory therapeutics.

(iii)

A genetic—or familial—component has been identified in many gastrointestinal disorders, including gastrointestinal malignancies, inflammatory bowel disease, susceptibility to Helicobacter pylori related pathology, pancreatitis, bile stone formation, and others.7,8

Progress in the different fields outlined above may rely to different extents on the availability of genomic information and technology.

Methodological problems in the systematic exploration of disease pathophysiology

Taking a cell biological hypothesis to a specific test has for a long time been the …