page_title: Sydney Brenner
section_title: Career and research
hierarchical_section_title: Sydney Brenner / Career and research
caption_attribution_description: English: E. Lederberg, G. Stent, S. Brenner, J. Lederberg, 1965. The original photo is owned by the Esther M. Zimmer Lederberg Estate. With the permission of that Estate's Trustee, Matthew Simon, I have adapted the photo for free use.
context_page_description: Sydney Brenner CH FRS FMedSci MAE was a South African biologist. In 2002, he shared the Nobel Prize in Physiology or Medicine with H. Robert Horvitz and Sir John E. Sulston. Brenner made significant contributions to work on the genetic code, and other areas of molecular biology while working in the Medical Research Council Laboratory of Molecular Biology in Cambridge, England. He established the roundworm Caenorhabditis elegans as a model organism for the investigation of developmental biology, and founded the Molecular Sciences Institute in Berkeley, California, United States.
context_section_description: Following his DPhil, Brenner did postdoctoral research at the University of California, Berkeley. He spent the next 20 years at the Laboratory of Molecular Biology in Cambridge. There, during the 1960s, he contributed to molecular biology, then an emerging field. In 1976 he joined the Salk Institute in California.
  Together with Jack Dunitz, Dorothy Hodgkin, Leslie Orgel, and Beryl M. Oughton, he was one of the first people in April 1953 to see the model of the structure of DNA, constructed by Francis Crick and James Watson; at the time he and the other scientists were working at the University of Oxford's Chemistry Department. All were impressed by the new DNA model, especially Brenner who subsequently worked with Crick in the Cavendish Laboratory at the University of Cambridge and the newly opened Medical Research Council (MRC) Laboratory of Molecular Biology (LMB). According to the late Beryl Oughton, later Rimmer, they all travelled together in two cars once Dorothy Hodgkin announced to them that they were off to Cambridge to see the model of the structure of DNA.
  Brenner made several seminal contributions to the emerging field of molecular biology in the 1960s (see Phage group). The first was to prove that all overlapping genetic coding sequences were impossible. This insight separated the coding function from structural constraints as proposed in a clever code by George Gamow. This led Francis Crick to propose the concept of the adaptor or as it is now known "transfer RNA (tRNA)". The physical separation between the anticodon and the amino acid on a tRNA is the basis for the unidirectional flow of information in coded biological systems. This is commonly known as the central dogma of molecular biology i.e. that information flows from nucleic acid to protein and never from protein to nucleic acid. Following this adaptor insight, Brenner proposed the concept of a messenger RNA, based on correctly interpreting the work of Elliot "Ken" Volkin and Larry Astrachan. Then, with Francis Crick, Leslie Barnett and Richard J. Watts-Tobin, Brenner genetically demonstrated the triplet nature of the code of protein translation through the Crick, Brenner, Barnett, Watts-Tobin et al. experiment of 1961, which discovered frameshift mutations.  This insight provided early elucidation of the nature of the genetic code. Leslie Barnett helped set up Sydney Brenner's laboratory in Singapore, many years later.
  Brenner, with George Pieczenik, created the first computer matrix analysis of nucleic acids using TRAC, which Brenner continued to use. Crick, Brenner, Klug and Pieczenik returned to their early work on deciphering the genetic code with a pioneering paper on the origin of protein synthesis, where constraints on mRNA and tRNA co-evolved allowing for a five-base interaction with a flip of the anticodon loop, and thereby creating a triplet code translating system without requiring a ribosome. This model requires a partially overlapping code. The published scientific paper is extremely rare in that its collaborators include three authors who independently became Nobel laureates.
  Brenner then focused on establishing Caenorhabditis elegans as a model organism for the investigation of animal development including neural development. Brenner chose this 1-millimeter-long soil roundworm mainly because it is simple, is easy to grow in bulk populations, and turned out to be quite convenient for genetic analysis. One of the key methods for identifying important function genes was the screen for roundworms that had some functional defect, such as being uncoordinated, leading to the identification of new sets of proteins, such as the set of UNC proteins.  For this work, he shared the 2002 Nobel Prize in Physiology or Medicine with H. Robert Horvitz and John Sulston.  The title of his Nobel lecture on December 2002, "Nature's Gift to Science", is a homage to this nematode; in it, he considered that having chosen the right organism turned out to be as important as having addressed the right problems to work on. In fact, the C. elegans community has g
caption: Esther Lederberg, Gunther Stent, Sydney Brenner and Joshua Lederberg pictured in 1965
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