Nature’s gift to neuroscience

In 1963, Sydney Brenner wrote a proposal to Max Perutz on tackling the next ‘big questions’ in molecular biology. Beginning with the postulate that simple organisms have many of the features that control development and physiology in more complex organisms, Brenner proposed ‘to tame a small metazoan’ to discover the ‘control mechanisms’ of development. Boldly, he proposed to identify and trace the lineage of every cell in a nematode worm. He was joined in this goal by John Sulston, who painstakingly produced the worm C. elegans cell lineages from single cell to adult. The product of this work, which was completed in the storied halls of the Medical Research Council’s Laboratory of Molecular Biology (MRC LMB), was transformative at the time and remains a valuable resource to this day. Among the many contributions of the lineage project, it led to the discovery of mechanisms of apoptosis with H. Robert Horvitz. For their work, Brenner, Sulston, and Horvitz shared the 2002 Nobel Prize in Physiology or Medicine.

Their work and the work of many others who joined their quest identified and refined the pertinent questions in molecular genetics and development, questions that Brenner wrote to Perutz needed to be defined before progress can be made. In the process, Brenner, Sulston, their F1s and succeeding generations generated ‘key unitary steps’ in the development and function of different animal organ systems, including those of the nervous system. John White, a Brenner graduate student, mapped the first neural connectome with the help of Eileen Southgate and Nichol Thomson. In this issue, White discusses how the C. elegans and human nervous systems are fundamentally similar. He proposes a roadmap into reconstructions of more complex nervous systems, using concepts defined in the worm.

This issue also contains the personal perspectives of several pioneers from the early days of the C. elegans community. Martin Chalfie details how a drive with Horvitz led him to a poster by Sulston on touch-insensitive mutants at the ‘First International C. elegans Meeting’, which hooked Chalfie on touch receptor neurons—his ‘Hershey Heaven’ that led him to pursue diverse fields. Robert Waterston and Donald Moerman beautifully captures Sulston’s spirit and passion for science, which Chalfie also highlights. Antony Stretton vividly describes his magical time in the early days of the LMB, with Brenner as a postdoctoral mentor. Catherine Rankin charmingly recounts her initial foray into C. elegans learning and memory after working on Aplysia.

This issue honors Brenner and Sulston for their contributions to the field of neuroscience. As Brenner had hoped in the 1960s, C. elegans has provided the foundation for many areas in neuroscience. This issue explores the C. elegans contributions to neuronal and glial development and circuit formation and their plasticity and diverse functions in health and disease. As new questions are defined, studies into C. elegans behavioral and physiological outputs in response to sensory inputs have also flourished. Here we also have a collection of articles that chronicles C. elegans sensory biology, aversive olfactory learning, aggression, social and sexual behaviors, sleep, survival programs, aging and neurodegenerative diseases. Indeed, C. elegans paved the way for the genetic study of aging, including how neurons might modulate aging or how age-dependent diseases affect the nervous system. We predict that C. elegans will continue to pave the way for solving ‘big questions’ in neuroscience, perhaps ushering the birth of more fields or re-birth of existing fields.

Brenner and Sulston’s contributions resonate beyond scientific concepts. They championed a tradition of open access and data sharing, which permeates the C. elegans community and contributes to its power in advancing scientific progress. Thus, we hope that the work and personal perspectives highlighted here serve as resources and inspiration to present and future generations of the C. elegans community and their friends in other neurogenetics community and beyond.

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Correction Statement

This article has been republished with minor changes. These changes do not impact the academic content of the article.