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Riddle DL, Blumenthal T, Meyer BJ, et al., editors. C. elegans II. 2nd edition. Cold Spring Harbor (NY): Cold Spring Harbor Laboratory Press; 1997.

Cover of C. elegans II

C. elegans II. 2nd edition.

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Preface

It is a pleasure for me to have the opportunity to begin this volume with a tribute to the large community of scientists who have been devoting their life to studies of Caenorhabditis elegans. Should this preface be read by individuals outside the scientific community, they may well wonder what it is that motivates the thousands of individuals around the world who spend 80 hours a week thinking and dreaming about this tiny nematode worm, only about 1 mm long and formed from 959 body cells. To the uninitiated, let me begin by making it clear that this is not one of those inexplicable personality cults. The person who started it all in 1965, Sydney Brenner, often exudes both karma and charisma in his monthly essay in the journal, Current Biology. Nevertheless, it is an attempt to understand the worm that grips and inspires those thousands of scientists—not Sydney.

I was fortunate to begin my own career in molecular biology at a time when the traditions of the early bacteriophage workers, led by Max Delbrück, still predominated. Our research was performed in a relatively small community of scientists, where most heads of laboratories knew each other well. Much data were freely shared, with the confidence that personal integrity would ensure proper credit for the source of new discoveries, without the need for priority established by a publication record. The enormous growth of our enterprise has eroded this feeling of trust during the past 35 years. But a strong tradition of sharing and trust persists in the worm community. In part, this is due to the stepwise growth of this field, which allows most worm researchers today to view themselves as being united through a close-knit lineage of former laboratory mentors. Most of the credit clearly belongs to those mentors themselves, who—starting with Sydney, John Sulston, and others—have set a high standard for both science and cooperation that their descendants have faithfully followed.

The cooperation and sharing in the worm community have played a major part in the success of everyone's science. The many shared C. elegans techniques, meetings abstracts, upcoming events, mutants, and DNA sequences can be viewed by all on the Internet (at http://eatworms.swmed.edu). In fact, this community's early effort at electronic sharing was selected as a “model collaboratory” in a publication from the Computer Science and Telecommunications Board of the National Research Council (National Collaboratories: Applying Information Technology for Scientific Research, 1993), the organization that I chair as president of the National Academy of Sciences.

The major assumption behind the Research Council report was that our marvelous new electronic communication tools will greatly speed up the science that is done in many different fields in the future. We can see why this is true when we review the driving force for the explosive development of biological knowledge in recent years. Science is fundamentally a knowlege-building process, in which each advance comes from combining units of previous knowledge in new ways. In short, the advance of scientific knowledge is all about making new connections. The more units of knowledge we have, and the more efficiently they are shared, the faster science proceeds. Biology is exploding both because with each passing year we have more knowledge to build on and because there is a great deal of sharing. Other factors being equal, those particular fields of biology in which the sharing is most efficient will move the fastest. In science, therefore, a tradition of good deeds is generally well rewarded.

Why should one study a worm? This simple creature is one of several “model” organisms that together have provided tremendous insight into how all organisms are put together. It has become increasingly clear over the past two decades that knowledge from one organism, even one so simple as a worm, can provide tremendous power when connected with knowledge from other organisms. And because of the experimental accessibility of nematodes, knowledge about worms can come more quickly and cheaply than knowledge about higher organisms.

Today, the most prominent of the model organisms are the bacterium Escherichia coli, the yeast Saccharomyces cerevisiae, the fruit fly Drosophila melanogaster, the plant Arabidopsis thaliana, the mouse, the human—and of course C. elegans. In each of these cases, the intensive study of the organism has led to the accumulation of enough knowledge about it that unexpected relationships between the genes and proteins of that organism are constantly being uncovered. These surprises are providing new insights into fundamental biological mechanisms that are of profound significance. In other words, unanticipated synergies cause the impact of our knowledge from the many individual studies on an organism to be much greater than the simple sum of its parts. In addition, over time, a large armament of powerful organism-specific methods are developed that become powerful research tools for everyone who is interested in the organism. For C. elegans, for example, recent years have seen the development of reliable methods for knocking out the function of any desired gene by either antisense RNA or transposon-mediated techniques, an essentially complete library of ordered cosmid clones that provides the DNA corresponding to any mapped gene, a complete three-dimensional lineage map of what each cell does in the developing embryo as a function of time, the ability to separate and isolate blastomeres from the early embryos, and the DNA sequence of 58 million of the total of 100 million nucleotide pairs in the nematode genome (through a transcontinental project scheduled for completion in late 1998).

When I stand back and consider what I have learned from the studies of C. elegans, what do I remember most? I think first of all of that famous lineage diagram, which traces the ancestry of all 959 cells back to the fertilized egg and tells us exactly which cell divided—and at what time—to produce every cell in the embryo and adult. That such a diagram can be made at all is enormously significant. It tells us that each cell in a multicellular organism can act like a precisely timed robot that constantly senses its environment and acts accordingly, having the ability to remember what it detected (and therefore where it was) earlier in the embryo and to change its pattern of cell determination according to this memory, including setting a precise time for its next cell division. It is as if there were a time-counting “computer” inside each cell that inputs present events, stores them in memory along with the inputs from past events, and then performs the calculations that makes the cell behave appropriately with regard to its subsequent behavior. In other words, I learned from C. elegans that each cell in a multicellular organism must be incredibly sophisticated with regard to its input, storage, and output devices. Such a cell deserves tremendous respect from scientists.

I have also learned that a cell has amazing abilities to determine its movements and its precise spatial patterning. During the course of the worm's development, certain cells will move one way and then another, marching their way through a host of other cells in the embryo with great precision. And the mapping of all 302 nerve cells and their interconnections has revealed a remarkable consistency in the exact pattern of their more than 7000 branching synaptic interconnections. This result provides dramatic proof that incredible spatial control is possible in a multicellular aggregate, and it has given me a new feeling for the abilities that cells have for sculpting space.

We have come to realize in recent years that the basic molecules that make life possible are nearly the same in all cells. So much so, that—to our surprise—we can learn an enormous amount about how a human develops from a fertilized egg by studying a model organism such as a worm. In fact, because worms are so much easier to study than humans, we can say with confidence that the fastest and most efficient way of acquiring an understanding of ourselves is to devote an enormous effort to trying to understand these, and other, relatively “simple” organisms.

In attempting to unscramble this wonderful puzzle of how life works, we have embarked on an intellectual adventure of the highest kind. By late 1998, when the genome sequence is completed, we will have the complete catalog of the 10,000 or so proteins from which a worm is made. Since we now know that most proteins function in groups of ten or more to form “protein machines,” this means that all the remarkable complexity of structure and behavior that we see in C. elegans is somehow possible with only about a thousand protein machines. Quite clearly, even a small living thing like a worm is by far more elaborate and fascinating than the most complicated human constructions that we can imagine on this planet.

Scientists who are investigating how cells work in an organism today know that they are on a true frontier, peering out across unknown and mysterious territory where many surprises are certain to be found. It is this realization that motivates so many biologists to live and dream about science, and it is this that explains the typical 80-hour weeks familiar to all of our families and colleagues.

Bruce Alberts

November 20, 1996

Copyright © 1997, Cold Spring Harbor Laboratory Press.
Bookshelf ID: NBK20139

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