Cell biology as a world view.

Cell biology, stated simply, is for me the most satisfactory level from which to understand biology. This view is not universally held. Some people may prefer the perspective of genes, molecular structure, physiology, or cladistics. But when I start from the perspective of cellular function, I feel I have the best panorama of life. I appreciate the molecular underpinnings, the process of embryonic development, the diverse uses of transcription and metabolism, the anatomical changes in ontogeny and phylogeny, physiological adaptability, and homeostasis. Even evolution, perhaps the most general theory in all of biology, seems less formal and pedantic when I can appreciate what it is about cells that allows for so much selectable variation. Sometimes I think we should replace Dobzhansky's famous dictum, “Nothing in biology makes sense except in the light of evolution” (Dobzhansky, 1973 ) with “Nothing in evolution makes sense except in the light of cell biology.” Marc Kirschner Of course, part of the reason that I feel this way is that my definition of cell biology blatantly appropriates whatever is necessary from genetics, genomics, biochemistry, and other fields. Cell biology should not, in my opinion, be defined by organelles or processes, by structures or by techniques, but the understanding that all of biology is built on the dynamic and adaptive capacity of the cell and that the best place to understand the brain, the immune system, and human disease is from the cellular level. This is not an original idea. The famous evolutionary biologist Sewell Wright (Wright, 1931 ) wrote, “The older writers on evolution were often staggered by the seeming necessity of accounting for the evolution of fine details … for example, the fine structure of all the bones … . Structure is never inherited as such, but merely types of adaptive cell behavior which lead to particular types of structure under particular conditions.” With an understanding of adaptive cell behaviors, evolution and all of life becomes real. Cell biology as a field is itself adaptive. What will it morph into in the next 50 years? Certainly, many of the standard areas will continue to develop. There is no reason why important investigations should end just because new opportunities open up elsewhere. But some things that were exciting a decade ago, will inevitably be less exciting, and—if the past is any judge—scientific careers will both justifiably and unjustifiably founder on the shifting currents of competing interests. There are no infallible guides. Might there be a battle between basic and applied cell biology? I hope not; both basic and applied questions can yield important insight. But we could have a struggle between long-term and short-term thinking. That would be sad, for today we are reaping the results of discoveries made decades before. My hope for the cell biology of the next 50 years is that it will be more eclectic than ever. I have recently found systems biology to be an exciting direction. I do not see this as a repudiation of my roots. I see it as widening the beachhead for cell biology. Perhaps it was the dynamic and stochastic features of cells and embryos that drove me, or questions of evolution, or a reawakened appreciation for more quantitative disciplines. I have been attracted by unanswered questions, exciting new techniques, and stuff I just always wanted to know. I am privileged to share with my new colleagues an appreciation of the cell. For students who may be seeking guidance from a cell biology veteran, I can do no better than urge them to avoid group thinking and remember Peter Medawar's famous quote (Medawar, 1967 ), “Scientists are people of very dissimilar temperaments doing different things in very different ways.” I hope that during the next 50 years cell biology will continue to reflect that diversity.