Friday, December 7, 2007

This Week's Citation Classic

Brenner S. 1974. The genetics of Caenorhabditis elegans. Genetics 77: 71-94.

Sidney Brenner is one of the founding fathers of molecular biology, having identified mRNA and the nature of the triplet code. Brenner, like other far-sighted scientists, felt that mo-bio was pretty played out by the late '60s and early '70s. Benzer switched to fruit fly behavior. Crick decided to study consciousness. Brenner decided to focus on behavior and development. In his Nobel speech, Brenner stated, "choosing the right organism for one’s research is as important as finding the right problems to work on."

Brenner certainly benefited from bacteriophage, the organism of choice for many molecular biologists, but he was drawn in that direction by Delbruck and the Phage Group. This time, now a mature scientist in his own right, Brenner had a chance to select an organism of his own. He chose wisely: Caenorhbabditis elegans. C. elegans is an ~1mm long bacteriophagous soil nematode. Large populations can be maintained in the laboratory on bacteria cultured on agar, and they have the added advantage of being almost entirely transparent (a huge benefit for neuronal studies).

Brenner's classic 1974 paper asked “How genes might specify the complex structures found in higher organisms?", a major problem in biology today as well as then. Brenner's approach was to link genetics with detailed studies at the cellular level, and introduced C. elegans as the worm of choice for this work.

As Brenner wrote, “Behaviour is the result of a complex ill-understood set of computations performed by nervous systems and it seems essential to decompose the question into two: one concerned with the question of the genetic specification of nervous systems and the other with the way nervous systems work to produce behaviour.”

Thus Brenner launched a two-pronged effort to map the genetics and complete structure of the worm. This effort succeeded marvelously. Today we have unprecedented knowledge of this humble beastie. The developmental fate of each of the worm's 959 cells has been determined. The patterns of connectivity for each of its 302 neurons has been completely mapped. Its entire genome has been sequenced (the first multicellular eukaryote to be sequenced).

Brenner's choice of study organism was enormously influential. I don't think there are many full-fledged biology departments around the country that don't have at least one "worm person". Brenner has produced an amazing legacy.

Some last thoughts...
I am still, at the age of 76, excited by scientific research and the prospect of what can be done in biology. Science is something one is tied to for life and one should never retire from anything until one has secured one's next job. The endless quest for knowledge will continue as long as humans exist.

Brenner won the Nobel Prize in 2002 for his contributions; his speech was wonderful and can be accessed here (video and text). Brenner wrote an autobiography here. Visit the Brenner lab here. The Worm Nation maintains a web presence here.

Image: C. elegans neurons expressing green fluorescent protein.


  1. Actually, Saccharomyces cerevisiae was the first eukaryotic organism whose genome was sequenced. C. elegans was the first multicellular eukaryote whose genome was sequenced.

  2. Yes, you are right Jason. I've corrected the post. Thanks for pointing that out.

  3. Interesting post. I saw Brenner talk a few years ago and he was making the case that model organisms are on the way out - the human is the only system we should be using for studying human genetics now...