History of research on Caenorhabditis elegans

The nematode worm Caenorhabditis elegans was first studied in the laboratory by Victor Nigon and Ellsworth Dougherty in the 1940s, but came to prominence after being adopted by Sydney Brenner in 1963 as a model organism for the study of developmental biology using genetics. In 1974, Brenner published the results of his first genetic screen, which isolated hundreds of mutants with morphological and functional phenotypes, such as being uncoordinated. In the 1980s, John Sulston and co-workers identified the lineage of all 959 cells in the adult hermaphrodite, the first genes were cloned, and the physical map began to be constructed. In 1998, the worm became the first multi-cellular organism to have its genome sequenced. Notable research using C. elegans includes the discoveries of caspases, RNA interference, and microRNAs. Six scientists have won the Nobel prize for their work on C. elegans.

Early research

C. elegans was first described in 1900 by Émile Maupas, who isolated it from soil in Algeria.[1] Ellsworth Dougherty proposed in 1948 that free-living nematodes of the sub-order Rhabditina might be useful for genetic study, noting their relative structural simplicity and invariant cell lineage (eutely).[2] Dougherty and Victor Nigon obtained the first mutant, from a laboratory culture of the closely related nematode Caenorhabditis briggsae.[3] However much of the early laboratory work on Caenorhabditis nematodes was directed towards the establishment of a defined axenic culture medium.[4]

Brenner's search for a new model system

By the early 1960s, Sydney Brenner had made several important contributions to molecular biology, notably a demonstration (with Francis Crick and other colleagues) that the genetic code is triplet in nature.[5] In June 1963, he wrote to Max Perutz, then the head of the MRC Laboratory of Molecular Biology, Cambridge, proposing future research:

It is now widely realized that nearly all the 'classical' problems of molecular biology have either been solved or will be solved in the next decade...Because of this, I have long felt that the future of molecular biology lies in the extension of research to other fields of biology, notably development and the nervous system...I would like to tame a small metazoan organism to study development directly. My ideas on this are still fluid and I cannot specify this in greater detail at the present time.

— Letter to Max Perutz, 5 June 1963[6]

By the end of that year, his thoughts were more concrete:

Part of the success of molecular genetics was due to the use of extremely simple organisms which could be handled in large numbers...We should like to attack the problem of cellular development in a similar fashion, choosing the simplest possible differentiated organism and subjecting it to the analytical methods of microbial genetics...We think we have a good candidate in the form of a small nematode worm, Caenorhabditis briggsiae...To start with we propose to identify every cell in the worm and trace lineages. We shall also investigate the constancy of development and study its genetic control by looking for mutants.

— Proposal to the Medical Research Council (UK), October 1963[6]

Brenner obtained C. elegans from Dougherty and began to study them in the laboratory by December 1963.[7]

Transgenesis

C. elegans is amenable to transgenesis, the process of introducing foreign genetic material into the genome.[8] The most frequent method for generating transgenic worms is to inject exogenous DNA into the syncytial germ line; biolistic transformation can also be used.[8]

See also

History of model organisms

References
  1. Maupas, Émile (1900). "Modes et formes de reproduction des nematodes". Archives de Zoologie Expérimentale et Générale. 8: 463–624. Retrieved 2009-05-27.
  2. Dougherty ec; Calhoun HG (January 1948). "Possible significance of free-living nematodes in genetic research". Nature. 161 (4079): 29. Bibcode:1948Natur.161...29D. doi:10.1038/161029a0. PMID 18900748.
  3. Nigon V, Dougherty EC (April 1950). "A dwarf mutation in a nematode; a morphological mutant of Rhabditis briggsae, a free-living soil nematode". J. Hered. 41 (4): 103–9. doi:10.1093/oxfordjournals.jhered.a106095. PMID 15428631.
  4. Ellsworth C. Dougherty; Eder Lindsay Hansen; Warwick L. Nicholas; J. Anthony Mollett; Evangeline A. Yarwood (1959). "Axenic Cultivation Of Caenorhabditis Briggsae (Nematoda: Rhabditidae) With Unsupplemented And Supplemented Chemically Defined Media". Annals of the New York Academy of Sciences. 77 (2): 176–217. Bibcode:1959NYASA..77..176D. doi:10.1111/j.1749-6632.1959.tb36901.x.
  5. Crick FH, Barnett L, Brenner S, Watts-Tobin RJ (December 1961). "General nature of the genetic code for proteins". Nature. 192 (4809): 1227–32. Bibcode:1961Natur.192.1227C. doi:10.1038/1921227a0. PMID 13882203.
  6. Brenner, Sydney (1988). "Foreword". In Wood, William Barry (ed.). The Nematode Caenorhabditis elegans. Cold Spring Harbor, N.Y: Cold Spring Harbor Laboratory. pp. ix–xiii. ISBN 0-87969-307-X.
  7. Brenner, Sydney (1963). "Dougherty, Ellsworth C. (Brenner requests C. elegans)". Sydney Brenner Papers.
  8. Frøkjær-Jensen, Christian; Davis, M. Wayne; Sarov, Mihail; et al. (May 2014). "Random and targeted transgene insertion in Caenorhabditis elegans using a modified Mos1 transposon". Nat. Methods. 11 (5): 529–34. doi:10.1038/NMETH.2889. PMC 4126194. PMID 24820376.
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