It was May 1985. Outside the laboratory, near Paris, nature was exulting in its colorful mid-spring glory. The last technical details and experimental pitfalls had been fixed in the preceding weeks. Now, the site-specific endonucleolytic activity of the intron-encoded protein that I had carefully engineered to express in Escherichia coli was detectable. According to my autoradiogram, it was cleaving the intron-less DNA exactly where I expected. This experiment opened the way to a series of yet unexpected developments, but for me it concluded a long and rather solitary quest. Long, because the route that led to the first intron-encoded homing endonuclease, I-Scel according to the present nomenclature, had started no less than 15 years before, from a peculiarity of mitochondrial inheritance in yeast. Solitary, because over this long period, the phenomenon that led to this discovery had remained a unique oddity of nature, limiting its interest for many. Indeed, after the discovery of I-Scel, it took 3 additional years before the next examples of homing endonucleases could be identified, suggesting the generality of the phenomenon. By this time, the enzymatic properties of I-Scel and its unusual specificity were already characterized, and it was clear that we were in the presence of a novel class of enzymes.
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