On May 26 of this year, Alan Wolffe was killed in a traffic accident. May 28th – just 2 days later – saw the publication of his last oeuvre as an editor: an issue of Oncogene Reviews devoted to chromatin remodeling. On behalf of his many friends and colleagues, we offer a tribute to the life and work of this remarkable man.

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Figure 1

Alan would have turned 42 this year – to all those who knew him, however, it was clear that he lived and worked to an internal clock that used a different unit of time – his actual age when converted to Earth years might well have been a hundred. How he managed to do so much so well in so little time is a mystery. His career began with biophysical studies with Ian Walker on nucleosomes as an undergraduate at Oxford University. He then went on to study gene regulation during amphibian development with JR Tata at the MRC in London during the early 1980s, and continued with justly famous work done with DD Brown at the Carnegie Institute of Embryology on the dyamics of selective 5S rDNA gene control during development in Xenopus (one of us has very fond memories of studying the Wolffe/Brown papers as contemporary classics in a first-year graduate school course). Alan then joined the NIH, where in a short 10 years, he managed to coordinate a strikingly productive research effort on literally every aspect of the biology of the nucleus. His stunning publication record of just the last 3 years reveals an extraordinarily broad palette of biochemical, structural, and functional studies on – among many other topics – the role of DNA methylation in regulating gene expression in normal and pathological states, chromatin modification and remodeling in transcriptional repression and activation, transcriptional control by nuclear hormone receptors, nuclear reprogramming, basal transcription machinery function during early development, and the molecular mechanisms of gene misregulation in disease, including cancer and Rett syndrome.

Eager for the challenge of studying the newly sequence human genome in its native form and excited at the opportunity to apply in a functional genomics setting his broad expertise in the biology of the nucleus, Alan spent the last year and a half of his life in Sangamo BioSciences. While there, he directed an effort to use synthetic transcription factors as therapeutic agents in human disease, in plant agriculture, and to continue dissecting the pathways of gene control in chromatin.

The concordance of his death and the coming out of the Oncogene review issue is tragic and poignant: Alan's encyclopeadic erudition was legendary – with stunning speed and facility he retrieved from memory references both obscure and renown. Alan's book, ‘‘Chromatin Structure and Function’’, now in its 3rd edition, an inimitably succint, cogent, stunningly comprehensive and clear distillation of data from more than 1700 references, remains, together with the many review and primary research articles he authored, an invaluable permanent record of his scientific achievement, his extraordinary breadth as a scholar, and his remarkable ability for synthetic thought on a subject where such synthesis is a dire necessity.

However deep the wound to science imparted by Alan's death, it pales by comparison to the enormity of the loss to Alan's family – his wife and his two young children. No verbal or written condolences can possibly do justice to the profoundity and sincerity of our feelings of sympathy for Liz, Max and Kate.

At the request of Liz Wolffe, The American Cancer Society (http://www.cancer.org), the Rett Syndrome Research Foundation (http://www.rsrf.org), and an educational fund for Alan's children (http://www.sangamo.com/4apw) will gratefully accept donations in Alan's memory.