Paul B. Sigler (1934-2000)

Paul Sigler suffered a sudden and fatal heart attack on January 11th while walking from his home in New Haven to his laboratory at Yale University. His unexpected death came as a shock to all who knew him, and is particularly distressing to those of us who were privileged to call him student, mentor or colleague. Paul's engaging personality, his intense enthusiasm and his passion for science will be missed by many. Paul's remarkable scientific versatility as chemist, structural biologist and crystallographer stems from his early training. He graduated summa cum laude in chemistry from Princeton University, and then trained in medicine at Columbia University. After completing both internship and residency at Columbia-Presbyterian Medical Center, he switched careers to pursue basic research. Paul was introduced to crystallography in David Davies' laboratory at the NIH, and he received his Ph.D. from the University of Cambridge in 1967 for his role in the structure determination of γ-chymotrypsin in collaboration with David Blow, Richard Henderson and Brian Matthews. As a faculty member of the University of Chicago, Paul conducted pioneering structural investigations of initiator tRNA^met, phospholipase A₂, and trp repressor. His career reached new heights of excellence after his move to Yale University in 1989 to become an HHMI investigator and Henry Ford II Professor of Molecular Biophysics and Biochemistry. In his last and most productive decade, Paul led a large and extremely capable group of young scientists in groundbreaking investigations of eukaryotic transcriptional control, transmembrane signaling, and protein folding.

Paul's ambition to understand biological phenomena in structural terms often challenged the limits of the crystallographic method, and was a driving force for many significant advances. His highly inventive mind and keen ability to motivate others created a fertile environment for scientific exploration. Paul liked to compare protein crystallography to a decathlon, where the competitor may excel in certain events, but must be proficient in each one. Paul was more often coach than competitor, but he had a deep understanding of the game, and an instinct for bringing out the best in his people. Among his many contributions are innovations in crystallization, preparation and analysis of heavy atom derivatives, cryogenic techniques, optics, data processing and density modification. In many ways Paul's laboratory defined the cutting edge of modern protein crystallography.

My first interactions with Paul were in the graduate course he taught at the University of Chicago in the spring of 1983. An enduring memory is the huge beaker of chalk he brought up to the classroom, with which he would illustrate every concept with incredible clarity and detail. Despite temperamental comments when the chalk would slip away from him, his love of the crystallographic method and his enthusiasm for its use shone through loud and clear. When I subsequently joined Paul's laboratory I discovered that the effort he took in the classroom was redoubled in the supervision of his graduate students and postdoctoral fellows. He would frequently leave handwritten notes, sometimes several pages long, with suggestions of how to get the experiment of the day to work. But he also insisted that we think for ourselves, rather than operate as 'trained baboons.' The message was often passionately delivered, and we all listened and matured as scientists. Beyond the experiment, Paul was a great conversationalist, a terrific party host, and a good friend.

Paul trained and nurtured over seventy students and postdocs, many of whom have gone on to independent scientific careers. He also had many warm and lasting relationships with scientists from around the globe. I am grateful to colleagues who have generously shared their memories of Paul to aid the writing of this tribute, which has been a labor of love. Paul's love for his family was obvious to us all, and we extend our deepest sympathies to his wife Jo, their five children and eight grandchildren.

Yale U. will honor Paul's memory by creating a permanently endowed lectureship in structural biology at Yale, which will be held by leading scientists who will be chosen as exemplars of the approaches and style that Paul represented. Please send contributions to Office of the Chair, Dept of Molecular Biophysics and Biochemistry, Yale U., PO Box 208114 , 260 Whitney Ave., New Haven, Connecticut 06520-8114. Checks should be made out to Yale University and marked 'Paul Sigler Lecture Fund'.