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[
Genetics,
1989]
Just over 21 years ago, in October of 1967, Sydney Brenner soaked a culture of hermaphroditic nematodes of the species Caenorhabditis elegans in a solution of ethyl methane sulfonate. A week later, examining their F2 descendants, he noticed a short, "dumpy" animal among the long, thin wild-type worms. The dumpy animal was picked to a separate culture plate and allowed to produce self-progeny, which were also dumpy: it was a true-breeding mutant. The new strain was given the name E1. Crosses with the parental wild-type strain showed that the mutant phenotype was due to a single autosomal recessive mutation - in modern nomenclature, allele
e1 of the gene
dpy-1.
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[
Int J Dev Biol,
2000]
1969 was a landmark year. But for me it was not Neil Armstrong's giant leap or Woodstock heralding the beginning of the end of the sixties that sticks in my mind. It was a visit I made to Cambridge to meet a "bloke who is starting a new project to study some sort of worm", as my head of department at the Medical Research Council's National Institute of Medical Research informed me...
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[
Science,
2002]
The nematode worm known as Caenorhabditis elegans is not much to look at. Just a millimeter long and transparent to boot, it is almost invisible to the naked eye. But in biological research the tiny worm looms large, providing a model system for studying everything from embryonic development to aging. Now, three researchers who pioneered the use of C. elegans as a model organism have won the Nobel Prize in Physiology or Medicine.
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[
Clin Med,
2003]
The recent award of a Nobel Prize to Sydney Brenner crowns an astonishingly distinguished scientific career. He must have come very close to winning it several times in the past. A colleague described him as 'a visionary who sees further into the future than anyone'. This is borne out by his decision - made 40 years ago - to study a one-millimetre long worm in detail to define the, biochemical and genetic control of its development and differentiation. The impact of these studies has been so profound, with a significant bearing on human physiology and disease, that over 400 laboratories worldwide have now adopted the worm as a research tool. In this article, a brief outline is given of his work on the worm and of some of the highlights of his brilliant career.
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[
Hist Philos Life Sci,
2000]
The transformation of embryology to developmental biology has been linked to the introduction of experimental approaches from molecular genetics to the study of development. This paper pursues this theme by analyzing the tools molecular biologists, moving from phage and bacterial genetics to the study of development in higher organisms, brought to their new field of investigations. The paper focuses on Sydney Brenner's move from molecular genetics to developmental biology. His attempt to turn the nematode worm Caenorhabditis elegans into a new tool for the study of development included a vast and ever expanding mapping program. Worm workers themselves did not distinguish sharply between mapping on the cellular, chromosomal or molecular level. Mapping, the paper argues, or more generally 'analytical/comparative' next to 'experimentalist' approaches (Pickstone) were not only part and parcel of Brenner's strategy to 'molecularize' the study of development, but also played a crucial role in 'classical' molecular biology.
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[
Philos Trans R Soc Lond B Biol Sci,
2015]
The article 'Structure of the nervous system of the nematode Caenorhabditis elegans' (aka 'The mind of a worm') by White et al., published for the first time the complete set of synaptic connections in the nervous system of an animal. The work was carried out as part of a programme to begin to understand how genes determine the structure of a nervous system and how a nervous system creates behaviour. It became a major stimulus to the field of C. elegans research, which has since contributed insights into all areas of biology. Twenty-six years elapsed before developments, notably more powerful computers, made new studies of this kind possible. It is hoped that one day knowledge of synaptic structure, the connectome, together with results of many other investigations, will lead to an understanding of the human brain. This commentary was written to celebrate the 350th anniversary of the journal Philosophical Transactions of the Royal Society.
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[
Ecol Dis,
1983]
Medical records concerning filarial diseases in Ceylon date from the account of Davy[1], though there are hints as to the more obvious manifestations in the old chronicles of the country, too. A first survey was conducted in 1912/1913 concentrating on urban areas, followed by a second survey in the 1930s with emphasis on the rural parts. The results displayed a remarkable distribution pattern: Wuchereria bancrofti, the so-called "urban type", concentrated in Galle and Matara towns, whereas Brugia malayi, the "rural type", widespread along the southwest coast from Matara to Negombo, plus isolated pockets in the northwest, central north, east and south. The survey of the 1930s lead to the supposition that the occurrence of B. malayi must have something to do with the distribution of certain water plants, a suspicion later on confirmed in that Pistia stratiotes in particular--but other water plants as well--are essential for the survival of the vector (Taeniorhynchus (Mansonia) uniformis) during its early (submersed) stages of development. A determined effort to remove the water plants from tanks etc. reduced the rural type with encouraging results. At the same time, a combination of factors, in particular the war-time sojourn of masses of troops from Africa, already infected by filarial diseases, in the southwestern coastal areas triggered off an unexpected spread of the urban type out of its early "bridge-heads" in Galle and Matara towns to invade the southwest coastal areas, and, later on, supported by increased population mobility, to advance further inland too. At present, there is no remedy within sight to give some hope to come to grips with this problem as the vector, Culex pipiens fatigans, is ubiquitous and finds suitable breeding grounds practically everywhere. Research into the history of filarial diseases in Ceylon points as far as B. malayi is concerned, to an invasion by a Malayan army under the Kalinga kings during the days of close relations between Ceylon and southeast Asia, i.e. during the 12th and 13th centuries, and as far as W. bancrofti is concerned, a Chinese army, invading the southern coast in the early 15th century, is made responsible. Filarial diseases in Ceylon present a particular interesting case of geomedical research; but inspite of encouraging results in fighting the rural type, i.e. B. malayi, the urban type, W. bancrofti, seems to remain a problem of public health in the island for the forseeable future.
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[
Chembiochem,
2003]
Thank you so very much for inviting me to be here. It gives me a mingled sense of humility at how much I owe to others, and of joy that the collective work on the worm has been recognised in this way.
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[
Stud Hist Philos Biol Biomed Sci,
2012]
This paper argues that the history of the computer, of the practice of computation and of the notions of 'data' and 'programme' are essential for a critical account of the emergence and implications of data-driven research. In order to show this, I focus on the transition that the investigations on the worm C. elegans experienced in the Laboratory of Molecular Biology of Cambridge (UK). Throughout the 1980s, this research programme evolved from a study of the genetic basis of the worm's development and behaviour to a DNA mapping and sequencing initiative. By examining the changing computing technologies which were used at the Laboratory, I demonstrate that by the time of this transition researchers shifted from modelling the worm's genetic programme on a mainframe apparatus to writing minicomputer programs aimed at providing map and sequence data which was then circulated to other groups working on the genetics of C. elegans. The shift in the worm research should thus not be simply explained in the application of computers which transformed the project from hypothesis-driven to a data-intensive endeavour. The key factor was rather a historically specific technology-in-house and easy programmable minicomputers-which redefined the way of achieving the project's long-standing goal, leading the genetic programme to co-evolve with the practices of data production and distribution.
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[
Genetics,
2002]
This article marks the 25th anniversary of a paper reporting the first sex-determination mutants to be found in the nematode Caenorhabditis elegans. The isolation of these mutants initiated an extensive analysis of nematode sex determination and dosage compensation, carried out by a number of laboratories over the subsequent decades. As a result, the process of sex determination is now one of the most thoroughly understood parts of C. elegans development, in both genetic and molecular terms. It has also proved to have interesting repercussions on the study of sex determination in other organisms.