John Sulston on The Importance of Worm Research
  John Sulston     Biography    
Recorded: 15 Jun 2005

So this is a tiny nematode worm, roundworm. It’s closely related to the rather nasty roundworms like Ascaris that animals carry in their intestines. If you say you’ve got worms, it means you’ve got nematodes in your gut, for example. There are also some extremely nasty agricultural parasites, tomato, they’re called eelworms very often and they affect potatoes, tomatoes, that family, and have to be combated. But these are not the reasons why we were working on this worm. This is a very small member of this family. It’s one millimeter long when it’s fully grown, and it’s actually an important part of the natural cycling in the soil. It sits in between the decay products of plants and animals, which in the end, through fungi end up in bacteria, and now are sort of building up into larger structures that sit in the soil. The worm basically eats bacteria. It can also eat small yeast. Any tiny thing that will fit in its mouth it will eat, actually, because it mechanically crushes. So things—and they have to be about a thousandth of a millimeter, one micron in size to go in its mouth. So that’s the worm, it sits there in the garden in the compost heap. But now why is it good for us? Well, first of all it breeds very fast and this sort of fits with its small size and the fact it takes advantage of breeding quickly when times are good. So in three days you go from egg through to another egg. It also doesn’t have very many cells; it has about a thousand cells in its body. And putting those two together means that you can study it very minutely, both through the light microscope – you can see right through it and see the individual cells with the right kind of optics. You can also slice the entire worm up into thin sections which can be looked at in the electron microscope, which means you can see all the details of its nervous system. All of this takes quite a lot of work, but it can be done and has been done. So you have this electron microscope-level anatomy of the worm. Then again, because you can breed it very fast, you can mutagenize it. That’s to say you can change the DNA at random and then very quickly find mutants. So all of these things together meant that it seemed an ideal animal to fit in between the single celled bacteria and yeasts that were being studied, and the more complex creatures like the fruit fly, which although very interesting and closer to us in terms of the variety of systems they have – for example they have blood, and some sort of skeleton, neither which the worm has – but nevertheless the small size and the way you can see all the cells means the worm is good. And the worm is particularly good then for looking at things at the cellular level: for discovering how one cell communicates with another, how one cell gives rise to its daughters, and therefore to the structure of the animal, how the cells interact, how they stick together and so on. And so the worm has really filled a very valuable niche in the spectrum of model organisms that we use to find out about biology. The other thing which the worm has done, as we were discussing earlier, is leading on genomics. And in a funny way that also has assured its place in the place of all the other organisms in this spectrum. Why? Because through the genomics we’ve learned how very, very powerful the unity of life is. This is just talking Darwin. I mean, you know, as the evidence accumulates for the theory of evolution ever since Darwin’s day, we understand more and more clearly that all organisms are related, and we can learn about one organism by looking at another. So that we can learn about one bit of mechanism in one organism, one in another, and put them together and say pretty much, ah yes, now we understand it. And this is very important for learning about ourselves. We can’t do experiments on people, but we can get lots of clues from other animals. But it’s particularly powerful at the DNA level, and nobody knew until the genomics program went forward in the ‘90s and up to the present day, just how closely related a single gene in one organism would be to another. So you could recognize genes going back four billion years to the first organism. So it’s not a theory, really a practical observation now, that life is one and has come from a single origin.

John Sulston was born in Buckinghamshire on 24 March 1942, the son of a Church of England minister and a schoolteacher. A childhood obsession with how things worked – whether animate or inanimate – led to a degree in Natural Sciences at the University of Cambridge, specialising in organic chemistry. He stayed on to do a PhD in the synthesis of oligonucleotides, short stretches of RNA. It was a postdoctoral position at the Salk Institute in California that opened Sulston's eyes to the uncharted frontiers where biology and chemistry meet. He worked with Leslie Orgel, a British theoretical chemist who had become absorbed in the problem of how life began. On Orgel's recommendation, Francis Crick then recruited Sulston for the Medical Research Council's Laboratory of Molecular Biology in Cambridge.

He arrived there in 1969, and joined the laboratory of Sydney Brenner. Brenner had set out to understand the sequence of events from gene to whole, living, behaving organism by studying the tiny nematode worm Caenorhabditis elegans.

For more than 20 years Sulston worked on the worm, charting for the first time the sequence of cell divisions that lead from a fertilised egg to an adult worm, identifying genetic mutations that interfere with normal development, and then going on to map and sequence the 100 million letters of DNA code that make up the worm genome.

The success of this last project, carried out jointly with Bob Waterston of Washington University in St Louis, led the Wellcome Trust to put Sulston at the head of the Sanger Centre, established in 1993 to make a major contribution to the international Human Genome Project. There he led a team of several hundred scientists who completed the sequencing of one third of the 3-billion-letter human genome, together with the genomes of many important pathogens such as the tuberculosis and leprosy bacilli.

As the leader of one of the four principal sequencing centres in the world, Sulston was a major influence on the Human Genome Project as a whole, particularly in establishing the principle that the information in the genome should be freely released so that all could benefit.

In 2000 Sulston resigned as director of the Sanger Centre (now the Wellcome Trust Sanger Institute), though he retained an office there for a few more years, continuing to work on the Human Genome Project publications and on outstanding problems with the worm genome.

Anxious to promote his views on free release and global inequality, he published his own account of the 'science, politics and ethics' of the Human Genome Project*, while adding his voice to influential bodies such as the Human Genetics Commission and an advisory group on intellectual property set up by the Royal Society. The same year he gave the Royal Institution Christmas Lectures for children on the topic 'The secrets of life'.

In 2002, John Sulston was awarded the Nobel Prize for Physiology or Medicine jointly with Sydney Brenner and Bob Horvitz, for the work they had done in understanding the development of the worm and particularly the role of programmed cell death.

The Common Thread by John Sulston and Georgina Ferry, Bantam Press 2002.

Taken from: 9/2/09 - AC Written by: Georgina Ferry John Sulston-Biography