Life and death

Death is part of life. As embryos unfold, many of the cells produced during their development will commit suicide. This is no birth defect, but a key process in the sculpture of sophisticated organs and limbs, a pruning process of sorts. The five digits on your hand were webbed in the womb before suicidal cells allowed the fingers to separate.  Scientists call it apoptosis or programmed cell death.

Our knowledge of apoptosis, we owe in great part to a tiny worm, no longer than a millimetre. This little nematode lives in abundance deep within our compost heaps, quietly feeding on the micro-organisms that decompose our food. Caenorhabditis elegans is not only common in nature, but has become a widely used model organism in the scientific world thanks to the foresight of Sydney Brenner.

“There were lots of jokes about Sydney's worm, and general scepticism about its chances of coming to anything,” explains Sir John Sulston, who together with Sydney Brenner and Robert Horvitz, was awarded the 2002 Nobel prize in Physiology or Medicine for their work on the development and controlled suicide of unwanted cells. “The scepticism seemed a pretty good recommendation to me,“ John recalls; “there's little point in doing what everybody else is doing.”

How did the discovery come about? “Sydney wanted to trace cells through development. We were largely focused on the egg, but at the time we couldn’t see much. However, the Nomarski microscopes in the lab allowed us to watch live specimens, so I started looking at the larvae. At first, this seemed even more difficult because they kept moving around. Then I realized I could let them go free and crawl between the top of a thin layer of agar and the cover slip. That allowed me to watch and draw their cells.

Seeing my first cell division was an exciting moment, and I felt positive about the possibilities of following cells as they divided in larvae. It soon became obvious that certain cells died and disappeared. The cell would start to look different and in half an hour, it resembled a raised disc; then it would rapidly shrink and gradually disappear. Programmed cell death was already known from other systems, but now in the worm it was both visible and predictable.”

But why would cells be born to die? “You can’t tell the difference between suicidal and normal cells until they get the signal to biodegrade. Cell deaths in the nematode are predictable because cell fate is often tightly linked to the fixed pattern of cell division. In the course of evolution, some of these fates may have become redundant, and cell death removes the unwanted cells.

Other cell deaths arise from competition between identical cells - for example, this can be a means of discarding unfertilised egg cells. Again, in the development of our own nervous system, we make many more nerve cells than we need. They all try to contact the muscles. The ones that don’t make it are programmed to die.”

What triggers the signal to biodegrade? “We know a lot more about this thanks to work done in Bob Horvitz’s lab. There’s a long chain of command. Each tissue has a set of signals that, in a cascade, eventually focus into the same pathway of death. There are a whole set of different triggers depending on the cell function. But whatever the cells, they stay alive until the signal comes and then they die.

Nowadays it is easier to discover which genes regulate the process, since all the genes in worms and humans have been sequenced. The big mystery now is how the individual components arising from DNA (proteins) self-assemble into shapes that lock together to make multiple components, eventually building up into us. The whole point about the worm is that many processes in tiny animals like worms are essentially similar in bigger ones.”

Extract from the Nobel Textiles catalogue, edited by Brona McVittie, Science Communicator, MRC Clinical Science centre.

To download a pdf version of the catalogue, please visit nobeltextiles.co.uk