• Robin W Carrell.
• Cambridge Institute for Medical Research, University of Cambridge, CB2 2XY, Cambridge, UK. rwc1000@cam.ac.uk
• COPD. 2004 Apr 1;1(1):71-84.

AbstractThe archetypal status of alpha(1)-antitrypsin in biology and medicine grew from the finding, thirty years ago, by Carl-Bertil Laurell, of the association of its deficiency with emphysema. In biology, alpha(1)-antitrypsin now provides the model for both the structure and the remarkable mechanism of the serpin protease inhibitors that control the key proteolytic pathways of the body. In medicine, the plasma deficiency of alpha(1)-antitrypsin has drawn attention to protease-antiprotease imbalance as a contributory cause of chronic obstructive pulmonary disease. But even more significantly, the finding that the common genetic deficiency of alpha(1)-antitrypsin was also associated with the development of liver cirrhosis introduced the new entity of the conformational diseases. The proposal that the same general mechanism was responsible for the best known of the conformational diseases, the common late-onset dementias, was controversial. It was vindicated however by the recent finding that a mutation, which results in the liver aggregation of alpha(1)-antitrypsin, also results in a typical late-onset dementia when it occurs in a brain-specific homologue of alpha(1)-antitrypsin. The extensive development of such diverse fields of studies, each based on alpha(1)-antitrypsin, is a measure of the encouragement Laurell gave to younger colleagues in the field. It also reflects the great advantage of linked contributions from clinical as well as basic sciences. Time after time, scientific controversies and deadlocks have been solved by landmark clinical cases, which have revealed unexpected findings and insights, within and beyond the fields of study.

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