Student Mephistopheles “Yet in each word some concept there must be.” “Quite true! But don't torment yourself too anxiously; For at the point where concepts fail, At the right time a word is thrust in there. With words we fitly can our foes assail, With words a system we prepare, Words we quite fitly can believe, Nor from a word a mere iota thieve.” Johann Wolfgang Goethe; Faust I

Approximately five decades ago it was recognised for the first time that chronic pancreatitis (CP) may cluster in selected families suggesting an inherited disorder in these patients.¹ However, the underlying genetic defect remained obscure for a long time. The discovery of cationic trypsinogen (PRSS1) mutations in CP families provided a first clue to the underlying disease mechanisms.² Subsequent studies revealed that PRSS1 mutations are also present in patients with idiopathic CP. Recently, mutations in the serine protease inhibitor, Kazal type 1 (SPINK1) gene, a pancreatic trypsin inhibitor, were identified as associated with idiopathic or hereditary CP: in 22 of 96 paediatric patients, a SPINK1 mutation was detected. In 18 patients, a substitution of asparagine by serine at codon 34 in exon 3 was found (N34S). Six patients were homozygous for this mutation.³ These findings suggest that pancreatitis may be the result of an imbalance of proteases and their inhibitors within the pancreatic parenchyma.

In this issue of Gut, Threadgold and coworkers⁴ and Drenth and colleagues⁵ describe mutational studies of SPINK1 in two large series with different types of chronic pancreatitis [see pages 675 and 682]. Threadgold et …