Alan Wolffe (1959–2001)

Alan Wolffe, an internationally recognized investigator in chromatin research, died May 26 as a result of injuries suffered in a traffic accident in Rio Di Janeiro, Brazil, where he was attending a scientific conference. Although widely recognized in the field, and a prolific contributor to the literature, Alan was only 41 years old. He is survived by his wife, Elizabeth, and two children, Max and Katherine. His untimely death has been a shock to the wide community of scientists whose lives he touched.Alan was born and raised in Burton-upon-Trent, a small village in Staffordshire, England. His father was a graduate of Oxford University in physics, but had returned to the village to manage a green-grocery. Alan worked there with his father in his youth. He also met and courted his life-long companion, Liz, in the village, where they were friends from an early age.Alan followed his father to Oxford for undergraduate studies. Evidence of his keen intellect emerged during the Oxford days. In addition to a strong academic performance, he was a member of his college's University Challenge Team, which appeared on national television in competitions similar to an American quiz program. He became an enthusiast of the board game Go, and also represented the university in competitions. After Oxford, he joined the laboratory of Prof. Jamshed Tata at the Medical Research Council at Mill Hill for Ph.D. studies. Here he formed the early interests in chromosome structure, developmental regulation, and endocrinology that remained the center of attention throughout his scientific life.For postdoctoral studies, Alan moved in 1984 to Don Brown's lab at the Carnegie Institute in Baltimore. It was during these years that Alan began to emerge as a force in the chromatin field. His experiments on transcription of 5S genes represented some of the earliest efforts to establish a well controlled in vivo/in vitro approach to transcription from nucleoprotein templates. He also began to have a major impact at meetings. Participants in chromatin gatherings quickly realized if you were going to have an argument with Alan, you'd better have your facts straight. His photographic memory and formidable analytical skills could bring a sense of excitement to otherwise pedestrian discussions.Figure 1Figure 1Figure 1Alan WolffeView Large Image | View Hi-Res Image | Download PowerPoint SlideAlan was recruited to the NIH initially as a junior investigator in the Lab of Molecular Biology, in the NIDDK, where he continued his interests in chromatin structure and function. His studies on the organization of DNA in the nucleosome structure were pioneering at the time. His findings on the altered periodicity in the DNA helical repeat at the pseudo dyad axis led to a new appreciation of the precision of histone/DNA interactions in the nucleosome, and presaged some of the subsequent results from the crystallization of the complete nucleosome structure. Although Alan's lab was located in NIDDK, his gifts were quickly recognized by the director of NICHD, who made the unusual decision to create a new laboratory in the NICHD with Alan as the director. Thus, he became at the age of 31 one of the youngest Lab Chiefs in the history of the NIH.The Laboratory of Molecular Embryology was quickly organized with Alan's characteristic vigor and intensity. He recruited a strong group of junior faculty, all of whom have now begun successful careers. The founding of LME coincided with what is now recognized as a golden age in chromatin research. Two separate processes of chromatin reorganization were linked to gene activation in the early 1990s, the covalent modification of histone tails, as well as the alteration in nucleosome structure by ATP-dependent chromatin modifying complexes. Alan and his colleagues were in the thick of the action during this period. Among many contributions, he identified a large complex in Xenopus (Mi-2) that contained both covalent modification and nucleosome remodeling activities, linking these potentially disparate functions. What most impressed many of us during this period, however, was Alan's ability to integrate and synthesize the whole of chromatin biology. When Ian Wilmut visited NIH to discuss the famous Dollie cloning experiment, it was Alan who introduced Ian and placed the work in context. His depth in the literature was unparalleled. He reviewed the field constantly, in many formats. His monograph, Chromatin, was widely read, and is now routinely utilized as an introduction to the field.In a move that surprised many, Alan left academic science for the biotech world in March of 2000, becoming Chief Scientific Officer of Sangamo, Inc. What seemed attractive to Alan in this unexpected shift were the resources that could be brought to bear on a problem in the commercial world. Thus, the real attraction for him was the opportunity to pursue science more effectively. In countless seminars, he introduced the pharmaceutical world to the concept that genes in real cells are organized in chromatin, and that effective modification of genetic activity would require working in the chromatin context. In this regard, Alan had become a great popularizer of the chromatin gospel. He could effectively communicate to audiences of diverse background, and was one of the best spokesmen for the field at large.Finally, on a personal note, Alan was simply fun to be with. He could discuss almost any subject at length, and sessions would often run to the wee hours of the morning. Although not particularly gifted as an athlete, he pursued recreational sports with the same competitive spirit he brought to science. His goal was to win, not to vanquish the opponent, but to bring fun and interest to the game. He played golf and squash, trying to keep in the game even when overmatched, and meeting defeat or victory alike with a friendly promise to return to the fray. This positive approach was characteristic of his science as well, where he was never overmatched. He wanted to understand the issue at hand, and his goal in contentious discussion was to get to the core of the matter, bringing all possible information and analysis to bear. This was a great gift. He will be missed.