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. 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 a hypothetical molecule (later identified as
transfer RNA or tRNA) that transfers the genetic information from RNA to proteins. Brenner gave the name "
adaptor hypothesis" in 1955. 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. information flows from nucleic acid to protein and never from protein to nucleic acid. Following this adaptor insight, Brenner conceived of the concept of
messenger RNA during an April 1960 conversation with Crick and
François Jacob, and together with Jacob and
Matthew Meselson went on to prove its existence later that summer. Then, with Crick,
Leslie Barnett, and
Richard 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. Brenner collaborating with Sarabhai, Stretton and Bolle in 1964, using
amber mutants defective in the
bacteriophage T4D major head protein, showed that the
nucleotide sequence of the
gene is co-linear with the amino acid sequence of the encoded polypeptide chain. Together with the decoding work of
Marshall Warren Nirenberg and others, the discovery of the triplet nature of the
genetic code was critical to deciphering the code. Barnett helped set up Sydney Brenner's laboratory in
Singapore, many years later. ,
Gunther Stent, Sydney Brenner and
Joshua Lederberg pictured in 1965 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 a free-living roundworm
Caenorhabditis elegans as a
model organism for the investigation of animal
development including
neural development. He 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
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 in 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 grown rapidly in recent decades with researchers working on a wide spectrum of problems. Brenner founded the
Molecular Sciences Institute in
Berkeley, California in 1996. He was also on the Board of Scientific Governors at
The Scripps Research Institute, as well as being Professor of Genetics there. A scientific biography of Brenner was written by
Errol Friedberg in the US, for publication by
Cold Spring Harbor Laboratory Press in 2010. This column was so popular that "Loose ends from Current Biology", a compilation, was published by Current Biology Ltd. and became a collector's item. Brenner wrote "
A Life in Science", a paperback published by
BioMed Central. He is also noted for his generosity with ideas and the great number of students and colleagues his ideas have stimulated. In 2017, Brenner co-organized a seminal lecture series in Singapore describing ten logarithmic scales of time from the
Big Bang to the present, spanning the appearance of multicellular life forms, the evolution of humans, and the emergence of language, culture and technology. Prominent scientists and thinkers, including
W. Brian Arthur,
Svante Pääbo,
Helga Nowotny and
Jack Szostak, spoke during the lecture series. In 2018, the lectures were adapted into a popular science book titled ''Sydney Brenner's 10-on-10: The Chronicles of Evolution'', published by Wildtype Books. Brenner also gave four lectures on the history of molecular biology, its impact on neuroscience and the great scientific questions that lie ahead. The lectures were adapted into the book,
In the Spirit of Science: Lectures by Sydney Brenner on DNA, Worms and Brains.
American plan and European plan The "American plan" and "European plan" were proposed by Sydney Brenner as competing models for the way brain cells determine their neural functions. According to the European plan (sometimes referred to as the British plan), the function of cells is determined by their
genetic lineage. According to the American plan, a cell's function is determined by the function of its neighbours after
cell migration. Further research has shown that most species follow some combination of these methods, albeit in varying degrees, to transfer information to new cells. ==Awards and honours==