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Unformatted text preview: Bioscience Reports, Vol. 23, Nos. 5 and 6, October and December 2003 ( 2004) NOBEL LECTURE 8 DECEMBER, 2002 Worms, Life and Death H. Robert Horvitz 1 I never expected to spend most of my life studying worms. However, when it became time for me to choose an area for my postdoctoral research, I was intrigued both with the problems of neurobiology and with the approaches of genetics. Having heard that a new genetic organism with a remarkably simple nervous system was being explored by Sydney Brennerthe microscopic soil nematode Caenorhabditis elegans I decided to join Sydney in his efforts. THE CELL LINEAGE After arriving at the Medical Research Council Laboratory of Molecular Biology (the LMB) in Cambridge, England, in November, 1974, I began my studies of C . elegans (Fig. 1) as a collaboration with John Sulston. John, trained as an organic chemist, had become a Staff Scientist in Sydneys group five years earlier. Johns aim was to use his chemistry background to analyze the neurochemistry of the nematode. By the time I arrived, John had turned his attention to the problem of cell lineage, the pattern of cell divisions and cell fates that occurs as a fertilized egg generates a complex multicellular organism. John could place a newly hatched C . elegans larva on a glass microscope slide dabbed with a sample of the bacterium Escherichia coli (nematode food) and, using Nomarski differential interference con- trast optics, observe individual cells within the living animal. In this way, he could follow cells as they migrated, divided and, in certain cases, died. That cells died as a normal aspect of animal development had been known by developmental biologists and neurobiologists for many years, and in 1964 Richard Lockshin and Carroll Williams had published a paper  in which they referred to such naturally-occurring cell death as programmed cell death. The study of this phenomenon was later to engage a substantial proportion of my scientific efforts. Johns initial analyses of the C . elegans cell lineage were focused on the developing larval ventral nervous system. I found his discoveries about the relation- ship between cell lineage and nerve cell fate very exciting: 12 neuronal precursor cells underwent the same pattern of cell division, and descendant cells with equivalent cell 1 Howard Hughes Medical Institute, McGovern Institute for Brain Research, Department of Biology, Massachusetts Institute of Technology, 77 Massachusetts Ave., Cambridge, MA 02139, U.S.A. 239 0144-8463 y 03 y 1000-0239 y 2004 Plenum Publishing Corporation 240 Horvitz Fig. 1. Caenorhabditis elegans adults. Hermaphrodite above, male below. John Sulston took these photographs, and I drew the diagrams. Bar, 20 m. From ....
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