Paul Nurse Cell Cycle Laboratory Imperial Cancer Research Fund 44 Lincoln’s Inn Fields around the same time, Kolliker realized that early embry-London WC2A 3PX onic cleavage represented a series of cell divisions pro-United Kingdom ducing cells that eventually became differentiated into various tissues and organs (for a great near contemporary account of cell work at this time, see Wilson, 1925). Only those exacting editors at Cell could seriously ask This idea was extended further during the 1870s and you to review the past century of cell cycle research 1880s by Pringsheim, Strasburger, and Hertwig (Sharp, and to predict the course of research for the next cen- 1921), who recognized that eggs and sperm were single tury, and to do it all in 10 pages! It is unrealistic to try cells which became joined together at fertilization, so to be comprehensive in such a review, and so I will even the most complex multicellular organisms passed focus on what I consider to be the important principles through a single celled stage. Thus, cell division was underlying the cell cycle, with less emphasis on detailed established as the basis of growth and development of descriptions of molecular mechanisms which would de- both animals and plants. generate into lists of genes and proteins. Referencing Improvements in microscopes and microscopic techwill be minimal, and will be restricted to reviews, a few niques led to a detailed description of the changes ockey primary publications, and to books written in English curring to the chromosomes during mitosis, the most for summaries of the earlier literature. conspicuous event of cell division. A critical feature ob-Let us begin at the end of the century by summarizing served by Flemming and Strasburger during the 1880s what is now known about the cell cycle. We know that was the appearance of elongate chromosomal threads the cell cycle is the universal process by which cells formed from the nucleus, which then split lengthways reproduce, and that it underlies the growth and develop- before shortening and thickening later in mitosis (Wilson, ment of all living organisms. The most important events 1925; Flemming, 1965). Van Beneden later showed that of the cell cycle are those concerned with the copying the longitudinal halves of each split chromosome sepaand partitioning of the hereditary material, that is repli- rated apart into the two daughter nuclei, and that the cating the chromosomal DNA during S phase and sepa- chromosomes of a fertilized nematode egg were derived rating the replicated chromosomes during mitosis. Con- in equal numbers from the egg and sperm. With this trols operate that regulate onset of these events and discovery, Weissman came to the important conclusion compensate for errors in their execution. The molecular that the chromosomes were the basis of heredity, and basis of these controls is highly conserved from simple that germ cells formed a continuous line of heredity unicellular eukaryotes such as yeast to complex metazo- between the generations (Sharp, 1921; Wilson, 1925). ans such as ourselves. The precision with which cell The link between the cell cycle and genetics was further cycle events are executed ensures the survival of living strengthened by the rediscovery of Mendel’s Laws of organisms, while loss of this precision increases geno-