Thirty-five years have now passed since the presence of the first homing en-donuclease was revealed by its consequences on the mitochondrial markers flanking the mobile intron. Even the most perfect molecular parasites have their weaknesses. The complicated story that led to this discovery is one that cannot be repeated. It has never been related before and I am pleased to do so in this book. If the yeast a intron had not been studied, other routes would have probably eventually led to these enzymes, given their widespread distribution in nature and modern molecular techniques and genomic strategies. However, it is unclear whether they would have been recognized as being as special as they are. We still do not exactly understand the origin and evolution of intron homing, but the prospect of applications of homing endonucle-ases for gene targeting and genome engineering has now raised considerable interest in them. It is quite possible that other biological phenomena as specific as intron homing and its nucleases exist in nature. Detecting them is the challenge for modern biology. Creating the environment for this to happen is the challenge for policy-makers.

Acknowledgements. During the long story that I have summarized in this chapter with my own personal bias, I had the chance to meet and interact with numerous people without whom the history of intron-encoded homing endonucleases would not have been the same. It is impossible for me to recall all of them. May the absent forgive me. Beside those personally cited in the text, I should mention particularly: P. Avner, B. Backhaus, H. Baranowska, A. Beauvais, L. Belcour, M. Bolotin-Fukuhara, H. Blanc, J. Boyer, J. Brosius, G. Burger, M.-P. Carlotti, G. Church, M. Claisse, D. Coen, A.M. Colson, G. Cottarel, F. Denis, J. Deutsch, G. Dujardin, M. Eck, E. Fabre, C. Fairhead, G. Faye, G. Fischer, F. Foury, B. Frey, L. Gaillon, N.W. Gilham, J.E. Haber, A. Harington, E. Heard, C. Jacq, N. Jacquesson-Breuleux, Z. Kotylak, A. Kruszewska, F. Lang, J. Lazowska, B. Llorente, E. Luzi, G. Michaelis, C. Monteilhet, R. Mori-moto, P. Netter, O. Ozier-Kalogeropoulos, S. Pellenz, A. Perrin, E. Petrochilo, A. Plessis, E. Pratje, G.-F. Richard, M. Ricchetti, C. Rougeulle, G. Schmitz, D. Schwartz, R. Schweyen, M. Soler, M. Somlo, A. Spassky, I. Stroke, H. Tettelin, M. Turmel, C. Vahrenholz, L. Weill, K. Wolf, and D. Worth. Some are no longer among us. They have all contributed to the saga of the first homing endonuclease, either directly by their experiments and efficient collaborations, or indirectly by their friendly discussions.

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