Caenorhabditis elegans: The model system that transformed research strategies worldwide.

Many heard about Caenorhabditis elegans (C. elegans) when they survived even as space shuttle Columbia was ripped apart in its final flight in 2003. But the legacy of this tiny nematode dates back to early 1960s.

Approximately 25,000 peer reviewed publications have used C. elegans as an experimental model organism. More than a thousand research papers have already been published in 2015 with work revolving around C. elegans.  It was the first multi cellular organism to have its entire genome sequenced and the only organism to have its neural connectome fully mapped. Between 2002 and 2008, three of the Nobel Prize winning discoveries were on C. elegans. Two encyclopedias on this organism have been published in 1988 and 1997 with numerous reprints which still serve as invaluable resources for researchers worldwide. Moreover, an online review portal, WormBook consolidates all the works done on C. elegans. There is even an extensive repository of the genomic, transcriptomic and proteomic data of C. elegans, WormBase, accessible globally to scientific curators. This is updated fortnightly, more frequently than any other molecular biology database in the world. Thousands of scientists and hundreds of millions of dollars are involved in C. elegans work around the globe. National Institutes of Health has a dedicated initiative for C. elegans research. For a 1mm non-parasitic nematode feeding on bacteria in rotten organic matter, it is an insignificant organism in nature. But why does the scientific community of life sciences and chemistry work so profoundly on it?

It was in 1963 that Sydney Brenner first proposed C. elegans as the model organism for his studies on the molecular and developmental biology of neural systems. The choice was very crucial. Brenner chose C. elegans for many reasons. He was immensely attracted by the very fact that thousands of this soil-dwelling nematode could be easily grown in a bed of E. coli in a petri dish within the laboratory unlike mouse, rats or higher animals. Moreover, being a hermaphrodite, these organisms self-fertilized and inbred 300-350 offspring per reproductive cycle of just three days. The added advantage came with the knowledge that, they could even be cross-bred with male worms for genetic hybrids. Only plant geneticists enjoyed the convenience of crossing and selfing till then. The total number of cells in the body of this worm is always fixed at 959 in an adult hermaphrodite and 1031 in the adult male. Of these 302 cells are consistently neurons. They form a primitive nervous system with a ‘brain’ of circumpharyngeal nerve ring. This can be easily traced with the contrast optics of serial section electron microscopy. The organism is thus equidistant from complexity and simplicity. The transparency of body gives the unique opportunity to track cellular differentiation and developmental processes even in the intact organism under a simple microscope. Anatomic simplicity, short life span of less than three weeks, fully sequenced 20,470 distinct genes with 50% homology to human genome and long term storage feasibility and easy transportability; C. elegans is one of the best model systems in experimental cellular biology.

Sydney Brenner, H Robert Horvitz and John E Sulston received the Nobel Prize in Physiology or Medicine in 2002 for their work in “genetic regulation of organ development and programmed cell death”. They found out that 131 cells present during the early embryonic stages of the worm were absent in the adult and traced these cell lineages throughout the life span of the worm to postulate their theories on the programmed cell death or apoptosis. Starting from the discovery of nuc-1 by Sulston and ced-3 and ced-4 by Horvitz, this paved way to the identification of many pro and anti apoptotic genes. Later, asymmetric cell division and the fate of each cell during embryogenesis was extensively mapped using C. elegans. DNA recombinations as well as DNA repair mechanisms have been described using the same model organism. Andrew Fire and Craig C Mello worked extensively on genetic interference by hybridization of exogenous double stranded RNA with endogenous mRNA transcripts (RNA interference; RNAi) in C. elegans which earned them the Nobel Prize in Physiology or Medicine in 2006. In fact, C.elegans is one of the first multi cellular transgenic animals created in laboratory settings. Peculiar gut granules of C. elegans emit fluorescence and even cause a fluorescence burst at the time of death of the worm. Martin Chalfie was awarded the Nobel Prize in Chemistry in 2008 for his work on green fluorescent proteins as a marker of gene expression. He did much of his work using C. elegans. From nucleotide base pairing in DNA to genetic basis of muscle atrophy in zero gravity space, C. elegans is helping researchers worldwide to understand the intricacies of molecular biology and genetics.

Interestingly, WormBase has declared prize worth $5000 to anyone who comes up with a better model organism than C. elegans!