Microbiology and Immunology

WORLD OF MICROBIOLOGY AND IMMUNOLOGY Brenner, Sydney

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not overlap. He demonstrated that an overlapping code would

put serious restrictions on the possible sequences of amino

acids. For example, in an overlapping code the triplet AAA,

coding for a particular amino acid, could only be followed by

an amino acid coded by a triplet beginning with AA—AAT,

AAA, AAG, or AAC. After exploring the amino acid

sequences present in naturally occurring proteins, Brenner

concluded that the sequences were not subject to these restric-

tions, eliminating the possibility of an overlapping code. In

1961, Brenner, in collaboration with Francis Crick and others,

confirmed his theory with bacteriophage research, demon-

strating that the construction of a bacteriophage’s protein coat

could be halted by a single “nonsense” mutation in the organ-

ism’s genetic code, and the length of the coat when the tran-

scriptionstopped corresponded to the location of the mutation.

Interestingly, Brenner’s original proof was written before sci-

entists had even determined the universal genetic code,

although it opened the door for sequencing research.

Also in 1961, working with Crick, François Jacob, and

Matthew Meselson,Brenner made his best-known contribution

to molecular biology, the discovery of the messenger RNA

(mRNA). Biologists knew that DNA, which is located in the

nucleusof the cell, contains a code that controlled the pro-

duction of protein. They also knew that protein is produced in

structures called ribosomesin the cell cytoplasm, but did not

know how the DNA’s message is transmitted to, or received

by, the ribosomes. RNA had been found within the ribosomes,

but did not seem to relate to the DNA in an interesting way.

Brenner’s team, through original research and also by clever

interpretation of the work of others, discovered a different

type of RNA, mRNA, which was constructed in the nucleus as

a template for a specific gene, and was then transported to the

ribosomes for transcription. The RNA found within the ribo-

somes, rRNA, was only involved in the construction of pro-

teins, not the coding of them. The ribosomes were like protein

factories, following the instructions delivered to them by the

messenger RNA. This was a landmark discovery in genetics

and cell biology for which Brenner earned several honors,

including the Albert Lasker Medical Research Award in 1971,

one of America’s most prestigious scientific awards.

In 1963 Brenner set out to expand the scope of his

research. For most of his career, he had concentrated on the

most fundamental chemical processes of life, and now he

wanted to explore how those processes governed development

and regulation within a living organism. He chose the nema-

tode Caenorhabditis elegans,a worm no more than a millime-

ter long. As reported in Science,Brenner had initially told

colleagues, “I would like to tame a small metazoan,” expecting

that the simple worm would be understood after a small bit of

research. As it turned out, the nematode project was to span

three decades, involve almost one hundred laboratories and

countless researchers, make C. elegansone of the world’s most

studied and best understood organisms, and become one of the

most important research projects in the history of genetics.

Brenner’s nematode was an ideal subject because it was

transparent, allowing scientists to observe every cell in its

body, and had a life cycle of only three days. Brenner and his

assistants observed thousands of C. elegansthrough every

stage of development, gathering enough data to actually trace

the lineage of each of its 959 somatic cells from a single

zygote. Brenner’s team also mapped the worm’s entire ner-

vous system by examining electron micrographs and produc-

ing a wiring diagram that showed all the connections among

all of the 309 neurons. This breakthrough research led Brenner

to new discoveries concerning sex determination, brain chem-

istry, and programmed cell death. Brenner also investigated

the genome of the nematode, a project that eventually led to

another milestone, a physical map of virtually the entire

genetic content of C. elegans.This physical map enabled

researchers to find a specific gene not by initiating hundreds

of painstaking experiments, but by reaching into the freezer

and pulling out the part of the DNA that they desired. In fact,

Brenner’s team was able to distribute copies of the physical

map, handing out the worm’s entire genome on a postcard-size

piece of filter paper.

Brenner’s ultimate objective was to understand develop-

ment and behavior in genetic terms. He originally sought a

chemical relationship that would explain how the simple molec-

ular mechanisms he had previously studied might control the

process of development. As his research progressed, however,

he discovered that development was not a logical, program-

driven process—it involved a complex network of organiza-

tional principles. Brenner’s worm project was his attempt to

understand the next level in the hierarchy of development. What

he and his assistants have learned from C. elegansmay have

broad implications about the limits and difficulties of under-

standing behavior through gene sequencing. The Human

Genome Project, for instance, was a mammoth effort to

sequence the entire human DNA. James Watson has pointed to

Brenner’s worm experiments as a model for the project.

Brenner’s research has earned him worldwide admira-

tion. He has received numerous international awards, includ-

ing the 1970 Gregor Mendel Medal from the German

Academy of Sciences, the prestigious Kyoto Prize from Japan,

as well as honors from France, Switzerland, Israel, and the

United States. He has been awarded honorary degrees from

several institutions, including Oxford and the University of

Chicago, and has taught at Princeton, Harvard, and Glasgow

Universities. Brenner is known for his aggressiveness, intelli-

gence, flamboyance, and wit. His tendency to engage in

remarkably ambitious projects such as the nematode project,

as well as his ability to derive landmark discoveries from

them, led Natureto claim that Brenner is “alternatively molec-

ular biology’s favorite son and enfant terrible.”

While still in Johannesburg in 1952, Brenner married

May Woolf Balkind. He has two daughters, one son, and one

stepson. In 1986, the Medical Research Council at Cambridge

set up a new molecular geneticsunit, and appointed Brenner

to a lifelong term as its head. Research at the new unit is cen-

tered on Brenner’s previous work on C. elegansand the map-

ping and evolutionof genes.

See alsoBacteriophage and bacteriophage typing; Genetic

code; Genetic identification of microorganisms; Genetic map-

ping; Microbial genetics

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