For what Brenner planned was to use the worm to discover how genes made bodies and then behaviour. And this was in 1965, before anyone had found and analysed a single gene for anything.
Yet elegans lives in tranquil obscurity underground, parasitising nothing, eating only bacteria and slime moulds.
Normally developing larvae spend only seven hours in the second stage of their lives, and most of this time is spent growing their gonads and eggs. But a worm that senses too many other worms around it, and too little food, will spend nearly twice as long as a second-stage larva, and in this time it will lay up fat in the cells of its skin and intestine rather than developing eggs. When next it moults, to become a level three larva, the dauer is immediately recognisable for the outside. It is thinner and darker than a normal worm. Their stomachs have closed up: in fact the mouth is completely closed by a block of the cuticle that normally forms the worm's outer skin, and the pharynx is shrunken. Their skin acquires a protective, water-repellent coating. In this stage, they can survive for up to three months, waiting for food to reappear. They are passive, but not inactive. Think of them as sulky adolescents, conserving their energy for some grand adventure which may never come. They will move quickly if touched, and they seek out water: when left in petri dishes in the lab, they crawl at night into the droplets of condensation that form inside the lids and there form huddles. But mostly they just lie around the agar, waiting for fate, or food.
As an invertebrate, elegans has no jaws or teeth. Instead it has a pharynx, a short, muscular tube with a round bulb or crushing chamber at the far end. Each section of the pharynx lies between three muscles running along its length. At rest, these muscles relax, constricting the tube between them into three folds like a Mercedes emblem in cross-section. When they contract, the sides of the pharynx spring apart to make a triangular tube, into which any liquid in front of the worm is sucked. When the muscles relax again, the liquid is expelled but any food particles it contains are trapped within the pharynx. It's odd to reflect that this is essentially the same method of feeding used by the largest animals on the planet, blue whales, who also suck their food in as liquid and then strain out the good bits. Whales, however, have visible strainers for their food. The worm has no strainers visible, even in an electron microscope. The separation may be accomplished by some exquisitely tuned turbulence in the liquid as it's pumped through this channel much thinner than a human hair.
From the worm's pharynx, the filtered-out bacteria move backwards to the grinding bulb at the end, lined with knobbly projections which crush open the bacteria, so their nutrients pass backwards into the gut, propelled at high pressure by the pumping muscles of the pharynx. The interior of the worm is pressurised: if you prick one it does not bleed but it will burst. This means that it needs no muscles in the intestine. All it needs to do it relax the muscle closing off the other end and everything left from digestion is expelled at the anus: the healthy worm defecates about every 45 seconds all its life.
Once fertilised, the embryo develops inside the eggs until it has grown to a tiny larva, which hatches once the eggs have been expelled form the vulva. Since the worm and its eggs are transparent, this process can actually be watched through a microscope as it happens
The mathematics of worm sex are simply mind boggling. I once tried to work out how many worms had laid down their lives for science in the last thirty years, and decided very rapidly that the number was incalculable. I mean that quite literally, and not just because my spreadsheet refused to contemplate them. The beginning of the calculation is quite easy to make: a worm will grow to maturity in about three and a half days. After that it will start laying eggs. Most will lay about 300 eggs in over the next four days; each of these will hatch in four days' time into a hermaphrodite that will lay another 300 eggs. So one worm has three hundred children and 90,000 grandchildren. These 90,000 worms would, if food were unlimited, produce 27 million children of their own. By the end of a month, assuming unlimited food and room, one worm could have eight thousand million living progeny, or, as an American would say, eight billion. There aren't that many people alive on earth. After the second month , each of those eight billion worms could have produced another eight billion descendants giving as the total number of possible descendants of one hermaphrodite in 69 days a figure that has 27 zeros after it. No wonder the spreadsheet boggled. When God promised Abraham descendants who would outnumber the stars in the sky or the grains of sand on a beach, he didn't mention that he had made the same promise to a worm first.
He did not at first seem destined for any sort of leadership. He came from the kind of high-minded middle-class background that you would nowadays find preserved largely among Quakers. His father was an army chaplain (an Anglican) who became the secretary of a rather low-church missionary society. His mother was a teacher of English. Like John White, he was a fiddler and a tinkerer as a child: a passion for clockwork seems to distinguish molecular biologists. More than any of the people I talked to, Sulston is unashamed about his pleasure in toys, in mechanisms, and what he calls that "artisanal" side of a scientist's work. He was the first man to learn the trick of freezing worms so they could be thawed out alive. Actually, this works best with very small larvae, but in any case, it was an absolutely necessary technical breakthrough if the worm was to become a reference animal for biology. Without the frozen reference stocks going back to the 1970s the worm could have been quietly evolving in laboratories or accumulating all kinds of deleterious mutations; but if that seems to be happening now, it is simple to wash away all the suspect worms and thaw out a fresh batch of the original vintage. Equally, the ability to freeze mutants of interest means that these are always available as soon as anyone needs to investigate one.
Now he is a neatly trimmed man, drawling seriously in a spacious and comfortable office at MIT. But in the Seventies he had the hair, the sideburns, and the heavy-framed glasses of the serious radical. The whole lab was full of counterculture in the early years, like everywhere else.
One of the reasons he had gone into biology was that he felt that economics was too remote from the real world. He wanted to change big things. He wanted to understand the brain. He thought that with a degree in maths and one in computation he was most of the way there, but a rigorous training in biological research was exactly what he wanted. Rigour - and excitement - were what he got. The genetic code had only been fully worked out in 1966, and he started in graduate school in 1968. Molecular biology was growing in ways that made it hugely exciting, and almost incomprehensible to an outsider, even one as clever and energetic as Horvitz: "I can remember sitting in courses in my first semester and I had no idea what people were talking about. I can remember thinking 'If I don't have a better idea at the end of the year, I'm doing something else', because I didn't think I had a chance in this business."
But he struggled on. By the end of the year, he had not only begin to understand what his lecturers were saying, he had found it was fascinating. But the phage he was working on were further from having a nervous system, and had less behaviour, even than the bacteria they preyed on. If he wanted to approach the problem brain, he would have to work on an animal, and the choice was between the fruit fly and the worm. The fly was more respectable, in scientific terms. But the worm seemed to him far more interesting, for all the reasons that had appealed to Sydney Brenner. Horvitz, like Brenner, wanted to hack at a nervous system with genetics, and the tiny, prolific worm had to be better for that than the large and relatively slow-breeding fly. That seemed obvious to him, even though there had not been a single paper published on it then, despite six years of work. Applications for a post-doctoral post are meant to be garnished with references to the scientific literature that show the student is entering a fruitful and interesting research project. Horvitz had one reference on his, and that was a "personal communication", scientese for gossip.
He had never met Sydney Brenner, nor been to the English Cambridge, but the woman he was living with had toured England earlier, and assured him that it was a beautiful city. That did it. He wrote to Sydney, found a post, and the couple crossed the Atlantic to his new job. As they got off the train, his girlfriend looked around her and announced that she had never seen the place before. She'd been thinking of Oxford all the time. Despite this setback, Horvitz thrived.
Once he had secured this degree, he reckoned he had better things to do in life than to make gadgets for other people. He was working on the ways in which nerve cells make connections and store memories, and at the same time beginning to dabble in computer graphics, but there didn't seem to be any research jobs available at the London MRC, so he applied for a job putting computers into telephone exchanges. Just as he was about to accept this, his boss in London told him that a man in Cambridge was interested in computer graphics, so he read up on DNA in Scientific American, put on his only suit, and went up for the interview, where he found Sydney Brenner chain-smoking in jeans and a Breton fisherman's shirt. "He didn't stop talking really. He talked to me all about these things he was going to do: cell biology, developmental biology, and how the nervous system works - all this sort of thing. It was really quite extraordinary. We shuffled around the labs and I was absolutely bombarded. As I left, he said, 'Well, you know, there'd be no trouble about you transferring because this is just another MRC appointment'."
By the late Sixties, Thomson was so good at preparing worms for the microscope that it became feasible to want to model it by making 20,000 slices through this creature which is only a millimetre long. The skill and dedication involved in such work was at least as great as that of anyone else in the project. Sydney, thought Nichol Thomson "a very talented lad" and was very keen to work with him; it's typical of the style of the MRC that when I asked Thomson whether anyone else in the world could have done his work, he replied "I don't know" in a tone suggesting the question was really difficult to answer.
Eileen Southgate had worked at the LMB since leaving school at sixteen in 1956 when she was offered the chance to help, as careers officer said, with medical research: "It was a choice of three jobs from school, actually. It was in the days when they came to the school with jobs and said, you know, you have a choice of three. One I couldn't get to, the other one I didn't really want and I chose this one. There was another girl there I'd been to school with, whom I knew, so …"
What did she like about it? "It was easygoing. It was then only, of course, a small group of about thirty people so it was very friendly, just like a family, really."
The New Scientist