Scott Emmons is Professor of Genetics and Professor of Neuroscience at the Albert Einstein College of Medicine. For the special issue of Philosophical Transactions B celebrating the 350th anniversary of the journal, he has written a commentary on one of the more recent (and certainly one of the longest) highlights from our archive, White et al.’s paper on ‘Structure of the nervous system of the nematode Caenorhabditis elegans’ (1986). Here he tells us a bit more about this ground breaking paper.
How was this a landmark paper?
This paper gave the first wiring diagram of the nervous system of an animal. This alone makes it a landmark. But further, it stimulated the growth of the field of C. elegans research. C. elegans has since joined the ranks of the major model organisms (E. coli, yeast, Drosophila, and mouse) that have given us modern biology.
Was C. elegans already a model organism or did this work establish its use?
This work together with Brenner’s genetic studies and John Sulston’s cell lineage work stimulated the use of C. elegans for investigating fundamental questions of biology. Work with C. elegans first began in the late 1940’s when it was determined how the sex of the animal is controlled by its chromosomal composition. At the time Brenner selected C. elegans, attempts were being made to establish its use for research on animal nutrition.
What tools did the authors have available to them? How does that compare to now?
Interestingly, some of the tools for determining nervous system connectivity available in the 1960’s have changed little over the decades since. I refer to the techniques of electron microscopy—fixing and staining the specimen, cutting ultrathin sections with a diamond knife, and acquiring the electron microscopic images. The quality of the original C. elegans electron micrographs set a standard researchers today strive to meet. Only recently have innovations in these techniques begun to appear. Other tools, by contrast, are of course profoundly more powerful today, notably the computational power of computers. Where this work was done with paper prints of the electron micrographs, colored pens, and everything written down by hand, nowadays everything is digitized and digital. It is enormously easier to handle the large amounts of information generated by research such as connectomics.
You spoke to one of the original authors, John White, during the writing of this paper. Did he tell you anything that surprised you about his research at the time? How did he feel about having his paper chosen as a landmark publication?
It was a bit surprising to learn how strongly both John White and Sydney Brenner felt personally the indifference, rejection even, with which their work was received by the community of neuroscientists when it first appeared. News of the selection of the paper as a landmark in the history of biology has been received with delight by all the C. elegans researchers I have spoken with.
Was the way research is being done today influenced by this work?
This paper was purely descriptive; a catalog, in this case of synaptic connections. Other large descriptive efforts in C. elegans research gave us a catalog of all the cells—a “parts list,” and a physical map of DNA clones anchored to the genetic map. Whereas at one time “purely descriptive” was a derogatory phrase, today its value is more widely recognized, and one even sees it glorified at times with a silly name, “discovery science”!
What discoveries are happening now in this field? What single question would you like to see answered?
We don’t know what discoveries are being made now. That’s why they will be discoveries. An outstanding question made more urgent by the connectomics work is the question of how connectivity in the nervous system, probably the most complex aspect of the multicellular phenotype, is coded in the genome. This is still largely unknown. It will be a profound day when we learn how it is that our behavior arises from our genes.
All commentaries, archive papers and supplementary files can be accessed for free. Check back at this blog for more Q&As, videos and blog posts over the coming months.