Walter Jakob Gehring: A master of developmental biology.

With Walter J. Gehring’s death in Basel on May 29, 2014, the scientific community lost one of the pioneers of molecular developmental biology. Walter will be missed by a large community of friends and colleagues, but he lives on in the work of the many scientists whom he had mentored and who now work in his and related fields. Walter J. Gehring, born in Zurich in 1939, became interested in developmental biology early on in his life as he watched beautiful butterflies emerging out of rather ugly pupae stored in a cardboard box given to him by his uncle. Walter went on to study bird migration for his diploma work, and then pursued doctoral studies with Ernst Hadorn, an eminent developmental geneticist teaching at the University of Zürich. Drosophila melanogaster was Walter’s experimental system, and transdetermination his thesis subject. At that time, his interest was caught by a Drosophila mutant, which carried an extra leg instead of the antenna on the fly head. The gene mutated in this stock later turned out to be Antennapedia (Antp), a homeotic gene responsible for the formation of the fly segment on which the second leg pair is formed. Walter called this remarkable Drosophila fly “Nasobemia.” In his own words, Nasobemia accompanied Walter through his life, and cloning of the underlying gene and finding out how mutation of a single gene could give rise to a new, fully developed structure in the wrong place, was a major aim of his research from this point onward. After obtaining his doctoral degree at the University of Zürich, Walter Gehring joined the laboratory of Alan Garen at Yale to learn about modern DNA research, and then moved to the newly founded “Biozentrum” at the University of Basel in 1972. With a solid background of cloning techniques, Walter and collaborators established the first Drosophila gene bank in Europe, and with Alfred Tissiere’s group at the University of Geneva identified and characterized several genes from this bank (1). Now, Walter’s major aim—to clone developmental regulatory genes—was coming closer. After an extended walk along the chromosome, the Antp gene of Drosophila was cloned in 1983 (2). The big surprise came when it turned out that Antp shared a 180-bp segment with other homeotic genes found in Drosophila (3) and other organisms, including humans (4). The homeobox was born, and it turned out that this stretch of DNA coded for the DNA-binding “homeodomain” of a wide variety of proteins. Walter Gehring was the initiator of an important episode in structural biology, which involved M.A. as his postdoctoral student and K.W. as an external collaborator. Because this work is less prominent in records about Walter than his contributions to molecular and cell biology, we describe here this part of his scientific life in some detail, as it is a nice illustration of Walter’s broad interest and unbeatable enthusiasm. On March 21, 1986, Walter and K.W., who had not met previously, listened to each other’s plenary lectures at the 18th Union of Swiss Societies for Experimental Biology (USGEB) Meeting in Basel. Walter talked about the homeobox and K.W. about protein structure determination by NMR. The following week, Walter called K.W. to inquire about possible interest to determine the structure of the Antp homeodomain with the then new and little proven NMR method. After being informed that milligram quantities of the highly purified protein would be needed, Walter apparently nurtured some doubts about the wisdom of his initiative, because his laboratory was used to work with at most micrograms of the Antp homeodomain.